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A decisao terapeutica deve ser baseada no risco cardiovascular considerando-se a presenca de fatores de risco, lesao em orgao-alvo e/ou doenca cardiovascular estabelecida, e nao apenas no nivel da PA. ABORDAGEM PARA NIVEIS DE PA ENTRE 130-139/85-89 mmHg A justificativa para intervencoes em pessoas com esses niveis de PA baseia-se no fato de que metade do onus atribuivel ocorre para pressoes sistolicas entre 130 e 150 mmHg, isto e, incluindo o comportamento limitrofe de PA1 (Grau B). Uma importante consideracao a [...]

Among the main etiologies of secondary arterial hypertension figure out the tumorous affections of adrenal gland, located on cortex - primary aldosteronism (Conn’s syndrome) and Cushing’s syndrome - or at glandular medulla - pheocromocytoma. Although these tumors are at most benign the surgical resection is needed in order to eliminate the disturbances provided by them and to limit the mass growth, being curative in about 80-90% of the cases. In this paper some particularities above surgical treatment of these diseases will be focused emphasizing the pre-operative prepare of the patients and the currently preconized approach.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:54:18Z No. of bitstreams: 1 Alessandra Saldanha Matheus Fernandes da Costa Tese completa.pdf: 2072165 bytes, checksum: 3ac25963d318def53c8076350f786fd4 (MD5) Made available in DSpace on 2021-01-06T20:54:18Z (GMT). No. of bitstreams: 1 Alessandra Saldanha Matheus Fernandes da Costa Tese completa.pdf: 2072165 bytes, checksum: 3ac25963d318def53c8076350f786fd4 (MD5) Previous issue date: 2016-03-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Endothelial dysfunction (ED) in Type 1 Diabetes (T1D), is a common denominator in the pathophysiology of microvascular and macrovascular complications and is an early marker of cardiovascular risk (CVR). Our aim were to determine the sensitivity and specificity of microcirculation (physiological and pharmacological) assessed through laser speckle contrast imaging (LSCI) and through levels of biomarkers (sVCAM-1 and sICAM-1) based on cutoff values derived from the reactive hyperemia index (RHI) through Endo-PAT, which identifies those with ED in T1D and secondarily to identify clinical, demographic and laboratory parameters associated with impaired endothelial function in these patients. Patients with T1D, aged ≥ 12 years underwent a clinical-epidemiological questionnaire. Were obtained fasting blood samples (lipid profile, glycemic control and levels of C-reactive protein) and at least two samples of urine were collected. Vascular reactivity was assessed in the forearm through the technique of LSCI at baseline, during post occlusive reactive hyperemia (PORH) and during iontophoresis of acetylcholine (ACh) with increasing anodic currents and peripheral arterial tonometry was performed by supplying the RHI through Endo-PAT device. Measurements of sVCAM-1 and sICAM-1 were perfomed though MULTIPLEX assays. 189 patients were evaluated, 97 women (51.3 %) with T1D, aged 32 ± 13 years and with a disease duration of 16 (6-21) years and mean HbA1c of 9.2% (± 2.2) . According to the Receiver Operating Characteristics curve (ROC) analisys, the only test of microvascular reactivity able to identify patients with ED according to RHI ≤ 1.67 was the AUC of ACh (p = 0.002) in those patients with T1D´s duration less than 5 years. The value of 10369 PU presented sensitivity and specificity of 65% and 87,5 %, respectively. No biomarker was able to detect ED through RHI-PAT. On the whole sample, no test of vascular reactivity was able to distinguish the ideal cuttoff based on RHI. The main variables correlated with RHI were age, age at diagnosis, duration of T1D, insulin dose (kg/day), systolic blood pressure (SBP) and capillary glycemia at the day of PAT test, A1c, CRP and glomerular flow rate (GFR). sVCAM-1 levels were correlated to sICAM-1, duration of T1D and capilar glycemia and the levels of sICAM-1 were correlated to AST and ALT. Area under curve (AUC) of PORH was correlated to cardiac frequency at the day of LSCI, AUC of ACh and any significant correlation was found between AUC ACh. In the present study, assessment of microcirculation through endothelium-dependent vasodilation to ACh using LSCI, could distinguish patients with ED according to PAT´s score, presenting sensibilitity and specificity of 65 and 87,5%, respectively, only in those patients with less than 5 years of T1D´s duration with the cuttoff value of 10369 PU, which we suggest to be ideal for this population. No biomarker was able to identify ED according to RHI. The most correlated variables to ED were age, age at diagnosis, duration of DM1, insulin dose (kg/day), systolic blood pressure (SBP) and capillary glycemia at the day of PAT test, A1c, CRP, GFR , AST and ALT. A disfunção endotelial (DE), no Diabetes Mellitus tipo 1 (DM1), aparece como um denominador comum na fisiopatologia das complicações micro e macrovasculares e representa um marcador precoce do risco cardiovascular (RCV). Nossos objetivos foram: determinar a sensibilidade e a especificidade da avaliação da microcirculação através da metodologia do laser speckle contraste por imagem (LSCI) e dos níveis dos biomarcadores (sVCAM-1 e sICAM-1) com base no ponto de corte do índice de hiperemia reativa (RHI) oriundo da tonometria arterial periférica (PAT), que caracterize a DE no DM1 e identificar os parâmetros clínicos, demográficos e laboratoriais associados ao comprometimento da função endotelial, nestes pacientes. Pacientes com DM1 e com idade ≥ 12 anos foram submetidos a um questionário clínico-epidemiológico. Amostras sanguíneas e urinarias foram coletadas para o perfil lipídico, controle glicêmico, níveis de proteína C-reativa e albuminúria. A reatividade vascular foi avaliada no antebraço através da técnica de LSCI no estado basal, durante a hiperemia reativa pós oclusiva (HRPO) e durante a iontoforese de Acetilcolina (ACh) com correntes anódicas crescentes e a PAT foi realizada fornecendo o RHI através do Endo-PAT. As dosagens de sICAM-1 e sVCAM-1 foram realizadas em ensaios multiplex (Tecnologia xMAP®). Foram avaliados 189 pacientes, sendo 97 mulheres (51,3 %), idade de 32 ± 13 anos, duração de doença de 16 (6-21) anos e média HbA1c 9.2% (±2.2). De acordo com a análise da curva Receiver Operating Characteristics (ROC), o único teste de reatividade microvascular capaz de identificar os pacientes com DE segundo o RHI ≤1,67 foi a AUC da ACh (p=0.002) naqueles pacientes com duração do DM1 inferior a 5 anos. O valor encontrado de 10369 PU apresentou sensibilidade e especificidade de 65% e 87,5%, respectivamente. Nenhum biomarcador foi capaz de detectar a DE segundo o RHI. Na amostra toda, nenhum teste da reatividade vascular foi capaz de detectar o ponto de corte ideal. As principais variáveis correlacionadas com o RHI foram: idade, idade ao diagnóstico, duração do DM1, dose de insulina kg/dia, PAS e glicemia capilar no dia da PAT, A1c, Taxa de Filtraçao Glomerular (TFG) e níveis de PCR. Os níveis de sVCAM-1 foram correlacionados com os níveis de sICAM-1, duração do DM e glicemia capilar e os níveis de sICAM-1 foram correlacionados com TGO e TGP. As principais variáveis correlacionadas com HRPO AUC foram: FC no dia do LSCI, ACh AUC. Nenhuma correlação houve com a ACh AUC. Na avaliação da microcirculação através da vasodilatação endotélio dependente, a ACh com a metodologia do LSCI, nesta amostra estudada, pôde distinguir os pacientes com DE de acordo com o Escore da PAT, apresentando sensibilidade e especificidade de 65 e 87,5%, respectivamente, somente naqueles pacientes com tempo de DM1 inferior a 5 anos com o ponto de corte de 10369 PU, que sugerimos ser o ideal para a população com DM1. Os parâmetros mais correlacionados com a DE foram: idade, idade ao diagnóstico, duração do DM1, dose de insulina (kg/dia), PAS, glicemia capilar no dia da PAT, A1c, TFG, níveis de PCR, TGO e TGP.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:41:56Z No. of bitstreams: 1 Fabiana Braunstein Bassan Dissertacao completa.pdf: 2094550 bytes, checksum: fb2f6d3eda24c9b55d4099f343e6fda2 (MD5) Made available in DSpace on 2021-01-05T19:41:56Z (GMT). No. of bitstreams: 1 Fabiana Braunstein Bassan Dissertacao completa.pdf: 2094550 bytes, checksum: fb2f6d3eda24c9b55d4099f343e6fda2 (MD5) Previous issue date: 2014-10-17 Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro Resistant hypertension (RH) is defined by the persistence of blood pressure (BP)≥140/90mmHg despite the use of 3 antihypertensive drugs at full doses, including a diuretic. Recent review of the literature shows few studies evaluating the profile and behavior of endothelial function in patients with RH. to evaluate endothelial function in resistant hypertensive patients. Cross-sectional study with 60 patients who were evaluated in a visit (V3) of a longitudinal study, where all patients initially had standardization of antihypertensive treatment. Patients with BP≥ 160/100mmHg and 0.05). Endothelial function assessed by the PAT showed reactive hyperemia index of 1.85±0.056 and 1.65+0.074 in CH and RH groups respectively (p = 0.036) and when evaluated by the biomarkers was observed: ICAM-1 (CH = 186.6+12.65ng/ml vs. RH= 240.9+23.76ng/ml, p= 0.038) VCAM-1 (CH= 627.1±37.09ng/ml vs. RH= 706.0±86.10ng/ml, p= 0.372), VEGF (CH= 403.3±94.91pg/ml vs.RH= 612.7±88.27pg/ml, p= 0.123) and MCP-1 (CH= 694.9±69.09pg/ml vs. RH=787.0±52.80pg/ml, p= 0.315). In the assessment of inflammatory biomarkers, was observed IL-6 in groups CH= 1.89±0.22pg/ml and RH= 9,79±4,41pg/ml (p= 0.027) and adiponectin in CH= 10570±1516pg/ml and RH= 1295 ± 8422pg/ml (p= 0.301). The prevalence rate of impaired endothelial function in the RH group was 54% (OR = 3.55; 95% CI 1.18 - 10.67; p= 0.029). Conclusions: in this study, the analyzes of variables at visit V3, showed that patients with RH have greater impairment of endothelial function than patients with CH. A hipertensão arterial resistente (HAR) é definida pela persistência da pressão arterial (PA)≥140/90mmHg a despeito do uso de 3 anti-hipertensivos em doses plenas, incluindo diurético. Revisão recente da literatura mostra poucos estudos avaliando o perfil e o comportamento da função endotelial em pacientes com HAR. Objetiva avaliar a função endotelial em pacientes hipertensos resistentes. Estudo transversal com 60 pacientes que foram avaliados em uma visita (V3) de um estudo longitudinal, onde numa primeira fase todos pacientes tiveram padronização do tratamento anti-hipertensivo. Foram incluídos pacientes (V0) com PA>160/100mmHg e 140/90mmHg acrescentou-se anlodipino 5mg/dia, foi realizado avaliação laboratorial de rotina do hipertenso e monitorização ambulatorial da PA-24h (MAPA). Visita 2: se PA>140/90mmHganlodipino foi titulado para 10mg/dia. Visita 3: todos os pacientes receberam avaliação clínica, da pressão arterial por MAPA, laboratorial de rotina e da função endotelial. Formaram-se dois grupos: os que controlaram a PA, grupo hipertensão arterial controlada (HAC); e os que permaneceram com PA de consultório>140/90mmHg e PA na MAPA-24h>130/80mmHg, foram considerados resistentes. O grupo HAR recebeu aleatoriamente espironolactona ou clonidina por mais 12 semanas para tentar controlar a PA e o grupo HAC teve assistência farmacológica mantida no mesmo período. A PA foi avaliada por método oscilométrico com aparelho digital semi-automático Microlife modelo BP3AC1-1PC e MAPA por aparelho SpaceLabs 90207. A função endotelial avaliada através de tonometria arteriolar periférica (PAT) pelo Endo-PAT2000® e por biomarcadores (I-CAM-1, V-CAM-1, VEGF, MCP-1, IL-6, adiponectina) através da técnica LuminexTMxMAP. Dos 60 pacientes avaliados, 36 controlaram a PA, grupo HAC, e 24 permaneceram resistentes ao tratamento, grupo HAR, na visitaV3. Na avaliação da PA pela MAPA-24h observamos que no grupo HAC a PAS-24h foi de 121,1+1,7mmHg e no grupo HAR 147+3,3mmHg, enquanto a PAD-24h no grupo HAC foi de 76,64+1,5mmHg e no grupo HAR 88,58+2,4mmHg (p 0,05). A função endotelial avaliada através do PAT mostrou índice de hiperemia reativa de 1,85±0,056 e 1,65+0,074 nos grupos HAC e HAR respectivamente (p= 0,036) e quando avaliada através dos biomarcadores observamos: ICAM-1 (HAC= 186,6+12,65 vs HAR= 240,9+23,76ng/ml, p= 0,038), VCAM-1 (HAC= 627,1±37,09vs HAR= 706,0±86,10ng/ml, p= 0,372),VEGF (HAC= 403,3±94,91 vs HAR= 612,7±88,27pg/ml, p= 0,123) e MCP-1 (HAC= 694,9±69,09 vs HAR= 787,0±52,80pg/ml, p= 0,315). Na avaliação dos biomarcadores inflamatórios, observamos IL-6 no grupo HAC= 1,897±0,2165pg/mle no HAR= 9,793±4,421pg/ml (p= 0,027) e adiponectina no grupo HAC= 10570±1516pg/ml e HAR= 8422±1295pg/ml (p=0,301). A razão de prevalência do comprometimento da função endotelial no grupo HAR foi de 54% (OR= 3,55; 95% IC 1,18- 10.67; p= 0,029). No presente trabalho, as análises das variáveis estudadas na visita V3, mostraram que os pacientes com HAR têm maior comprometimento da função endotelial que os pacientes com HAC.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:41:46Z No. of bitstreams: 1 Luciene da Silva Araujo Dissertacao Completa.pdf: 3721585 bytes, checksum: 3e1fdade0dd0055418d096bacc7c77b7 (MD5) Made available in DSpace on 2021-01-05T19:41:46Z (GMT). No. of bitstreams: 1 Luciene da Silva Araujo Dissertacao Completa.pdf: 3721585 bytes, checksum: 3e1fdade0dd0055418d096bacc7c77b7 (MD5) Previous issue date: 2014-06-10 Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro Introduction: obstructive sleep apnea (OSA) is considered a risk factor for cardiovascular disease. The mechanisms responsible for the development of atherosclerosis triggered by OSA are not completely known. However, there is evidence that OSA is associated with increased oxidative stress, higher levels of inflammatory mediators, insulin resistance, increased sympathetic nervous system activity, elevated blood pressure (BP) and endothelial dysfunction. Objective: to evaluate the relation of OSA with endothelial function, oxidative stress, inflammatory biomarkers, metabolic profile, body adiposity, sympathetic activity and BP in obese individuals. Methods: cross-sectional study involving 53 obese patients with body mass index (BMI) > 30 and < 40 kg/m2, without distinction of race and gender, aged between 20 and 55 years. The sleep study was performed with the equipment Watch-PAT200® and the diagnosis of OSA was made when apnea-hipopnea index (AHI) ≥ 5 events/h. All participants underwent evaluation of: body adiposity (weight, % body fat and circumferences of waist, hip and neck); BP; sympathetic nervous system activity (plasma levels of catecholamines); inflammatory biomarkers (high sensible c-reactive protein (hs-CRP) and adiponectin); oxidative stress (malondialdehyde); metabolism of glucose (glucose, insulin and HOMA-IR) and lipids (total cholesterol and fractions and triglycerides); and endothelial function (reactive hyperemia index (RHI) evaluated by Endo-PAT 2000® and cellular adhesion molecules). Statistical analysis was performed with software STATA version 10. Results: of the 53 evaluated patients, 20 were included in the group without OSA (Control group; CG) (AHI: 2.55±0.35 events/h) and 33 in the group with OSA (OSAG) (IAH: 20.16±3.57 events/h). The mean age (39.6±1.48 vs. 32.5±2.09 years) and the percentage of male participants (61% vs. 25%) were significantly higher in OSAG than in CG (p=0.01). The OSAG compared the CG showed significantly higher values of neck circumference (NC) (40.98±0.63 vs. 38.65±0.75 cm, p=0.02), glucose (92.54±1.97 vs. 80.2±1.92 mg/dL, p=0.0001), systolic BP (126.05±1.61 vs. 118.16±1.86 mmHg, p=0.003) and noradrenaline (0.16±0.02 vs. 0.12±0.03 ng/mL, p=0.02). After adjustment for confounders, glucose and hs-CRP were significantly higher in OSAG. Both groups presented similar values of BMI, insulin, HOMA-IR, lipid profile, adiponectin, diastolic BP, adrenaline, dopamine, adhesion cellular molecules and malondialdehyde. Endothelial function evaluated by RHI was also similar in both groups (OSAG: 1.85±0.2 vs. CG: 1.98±0.1, p=0.31). In correlation analysis, considering the whole group of patients, AHI presented a positive and significant association with NC and hs-CRP after adjustments for confounders. The minimum oxygen saturation was associated negatively and significantly with NC, insulin and HOMA-IR even after adjustments for confounders. Conclusions: the present study suggests that in obese individuals, OSA is associated with higher values of glucose and inflammation; higher AHI presents significant association with central adiposity and with inflammation; and lower oxygen saturation is associated with insulin resistance. Introdução: a apneia obstrutiva do sono (AOS) é considerada um fator de risco para as doenças cardiovasculares. Os mecanismos responsáveis pelo desenvolvimento da aterosclerose potencializados pela AOS não são completamente conhecidos. Entretanto, existem evidências de que a AOS está associada com aumento no estresse oxidativo, elevação nos mediadores inflamatórios, resistência à insulina, ativação do sistema nervoso simpático, elevação da pressão arterial (PA) e a disfunção endotelial. Objetivo: avaliar a relação da AOS com a função endotelial, o estresse oxidativo, os biomarcadores inflamatórios, o perfil metabólico, a adiposidade corporal, a atividade simpática e a PA em indivíduos obesos. Métodos: estudo transversal envolvendo 53 pacientes obesos, com índice de massa corporal (IMC) ≥ 30 e < 40 Kg/m2, sem distinção de raça e gênero, apresentando idade entre 20 e 55 anos. O estudo do sono foi realizado com o equipamento Watch-PAT 200®, sendo feito o diagnóstico de AOS quando índice apneia-hipopneia (IAH) ≥ 5 eventos/h. Todos os participantes foram submetidos à avaliação do (a): adiposidade corporal (peso, % gordura corporal e circunferências da cintura, quadril e pescoço); PA; atividade do sistema nervoso simpático (concentrações plasmáticas de catecolaminas); biomarcadores inflamatórios (proteína C reativa ultrassensível (PCR-us) e adiponectina); estresse oxidativo (malondialdeído); metabolismo glicídico (glicose, insulina e HOMA-IR) e lipídico (colesterol total e frações e triglicerídeos); e função endotelial (índice de hiperemia reativa (RHI) avaliado com o equipamento Endo-PAT 2000® e moléculas de adesão celular). A análise estatística foi realizada com o software STATA versão 10. Resultados: dos 53 pacientes avaliados 20 foram alocados no grupo sem AOS (grupo controle; GC) (IAH: 2,55±0,35 eventos/h) e 33 no grupo com AOS (GAOS) (IAH: 20,16±3,57 eventos/h). A faixa etária (39,6±1,48 vs. 32,5±2,09 anos) e o percentual de participantes do gênero masculino (61% vs. 25%) foram significativamente maiores no GAOS do que no GC (p=0,01). O GAOS em comparação o GC apresentou valores significativamente mais elevados de circunferência do pescoço (CP) (40,98±0,63 vs. 38,65±0,75 cm; p=0,02), glicemia (92,54±1,97 vs. 80,2±1,92 mg/dL; p=0,0001), PA sistólica (126,05±1,61 vs.118,16 ± 1,86 mmHg; p=0,003) e noradrenalina (0,16±0,02 vs. 0,12±0,03 ng/mL; p=0,02). Após ajustes para fatores de confundimento, a glicose e a PCR-us foram significativamente mais elevadas no GAOS. Os 2 grupos apresentaram valores semelhantes de IMC, insulina, HOMA-IR, perfil lipídico, adiponectina, PA diastólica, adrenalina, dopamina, moléculas de adesão celular e malondialdeído. A função endotelial avaliada pelo RHI também foi semelhante nos 2 grupos (GAOS:1,85±0,2 vs. GC:1,98±0,1; p=0,31). Nas análises de correlação, considerando todos os participantes do estudo, o IAH apresentou associação positiva e significativa com CP e PCR-us após ajustes para fatores de confundimento. A saturação mínima de O2 se associou de forma negativa e significativa com a CP, os níveis séricos de insulina e o HOMA-IR, mesmo após ajustes para fatores de confundimento. Conclusões: o presente estudo sugere que em obesos a AOS está associada com valores mais elevados de glicemia e inflamação; o aumento do IAH apresenta associação significativa com a obesidade central e com a inflamação; e a queda na saturação de oxigênio se associa com resistência à insulina.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:57:59Z No. of bitstreams: 1 Julia Freitas Rodrigues Fernandes Dissertacao completa.pdf: 5324879 bytes, checksum: 63f322397e39291fbe402a4ea86fcdd8 (MD5) Made available in DSpace on 2021-01-06T20:57:59Z (GMT). No. of bitstreams: 1 Julia Freitas Rodrigues Fernandes Dissertacao completa.pdf: 5324879 bytes, checksum: 63f322397e39291fbe402a4ea86fcdd8 (MD5) Previous issue date: 2014-03-27 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Nutritional intervention for weight loss is one of the treatment options for obstructive sleep apnea (OSA) in patients with excess body adiposity. However, the effects of moderate energy restriction, recommended by current guidelines for the treatment of obesity, on OSA are not yet known. To evaluate the effects of moderate energy restriction on the body adiposity; severity of OSA; blood pressure; sympathetic activity; oxidative stress; inflammatory biomarkers; metabolic profile and endothelial function in obese patients with OSA. Methods: A 16-week randomized clinical trial, involving 21 subjects with obesity (grade I or II), aged 20-55 years and presenting an apnea/hipopnea index (AHI) > 5 events/h. Participants were randomized into 2 groups: 11 in the energy restriction group (ERG) and 10 in the control group (CG). The ERG was instructed to follow an energy-restricted diet (-800 kcal/day) and the CG was advised not to change their food intake. At the beginning and at the end of the study, participants underwent evaluation of: OSA with the equipment Watch- PAT200® including the determination of the following parameters of OSA severity: AHI, minimum O2 saturation, number of O2 desaturations >4%; body adiposity (weight, %body fat and circumferences of waist, hip and neck); blood pressure (BP); sympathetic nervous system activity (plasma levels of catecholamines); inflammatory biomarkers (c-reactive protein and adiponectin); oxidative stress (malondialdehyde); metabolism of glucose (glucose, insulin and HOMA-IR) and lipids (total cholesterol and fractions and triglycerides); and endothelial function (index of reactive hyperemia evaluated by Endo - PAT 2000® and cellular adhesion molecules). The statistical analysis was performed with the software STATA v. 10. The level of statistical significance was p < 0.05. Results: The ERG, compared to the CG, presented significantly greater reduction in body weight (-5.57±1.81 vs. 0.43±1.21kg, p4% (-33.70±15.57 vs. 1.80 ± 7.85, p=0.04), in plasma concentrations of adrenaline (-12.70±3.00 vs. -1.30±3.90pg/mL, p=0.04); and significantly greater increase in minimum O2 saturation (4.60±1.55 vs. -0.60±1.42%, p=0.03). The ERG, in comparison with the CG, showed a greater decrease, however without statistical significance, in systolic BP (-4.23±1.95 vs. 2.34±1.39mmHg, p=0.05), in insulin levels (-5.11±1.93 vs. -0.65±1.28µU/mL, p=0.07) and HOMA-IR (-1.15±0.49 vs. -0.08±0.33, p=0.09). During the study period, the modifications in total and central adiposity presented a significant correlation with changes in parameters of OSA severity; in systolic and diastolic BP; and in insulin levels and in HOMA-IR, even after adjustments for confounding factors. The changes in central adiposity were significantly associated with modifications in levels of norepinephrine and adiponectin. The changes in parameters of OSA severity presented significant association with the modifications in serum levels of C-reactive protein. This study suggests that in obese patients with OSA moderate energy restriction is able to reduce total and central adiposity, parameters of OSA severity and sympathetic nervous system activity. A intervenção nutricional para perda ponderal é uma das opções terapêuticas para a apneia obstrutiva do sono (AOS) em pacientes com excesso de adiposidade corporal. No entanto, os efeitos da restrição energética moderada, recomendada pelas diretrizes atuais para o tratamento da obesidade, sobre a AOS ainda não são conhecidos. Avaliar em indivíduos obesos com diagnóstico de AOS os efeitos da restrição energética moderada sobre a adiposidade corporal; gravidade da AOS; pressão arterial; atividade simpática; estresse oxidativo; biomarcadores inflamatórios; perfil metabólico e função endotelial. Ensaio clínico randomizado, com duração de 16 semanas, envolvendo 21 indivíduos obesos grau I ou II, apresentando idade entre 20-55 anos e índice de apneia/hipopneia (IAH) > 5 eventos/h. Os participantes foram randomizados em 2 grupos: 11 no grupo restrição energética (GRE) e 10 no grupo controle (GC). O GRE foi orientado a realizar restrição energética (-800 Kcal/dia) e o GC não modificou sua ingestão alimentar. No início e ao final do estudo, os participantes foram submetidos à avaliação do (a): AOS com o equipamento Watch-PAT 200® incluindo a determinação dos seguintes parâmetros de gravidade da AOS: IAH, saturação mínima de O2, número de dessaturações de O2>4%; adiposidade corporal (peso, % gordura corporal e circunferências da cintura, quadril e pescoço); pressão arterial (PA); atividade do sistema nervoso simpático (concentrações plasmáticas de catecolaminas); biomarcadores inflamatórios (proteína C reativa e adiponectina); estresse oxidativo (malondialdeído); metabolismo glicídico (glicose, insulina e HOMA-IR) e lipídico (colesterol total e frações e triglicerídeos); e função endotelial (índice de hiperemia reativa avaliado com o equipamento Endo-PAT 2000® e moléculas de adesão). A análise estatística foi realizada com o software STATA v. 10. O nível de significância estatística adotado foi p4% (-33,70±15,57 vs. 1,80±7,85, p=0,04); nas concentrações plasmáticas de adrenalina (-12,70±3,00 vs. -1,30±3,90pg/mL, p=0,04); além de aumento significativamente maior na saturação mínima de O2 (4,60±1,55 vs. -0,60±1,42%,p=0,03). O GRE, em comparação com o GC, apresentou maior redução, porém sem alcançar significância estatística, na PA sistólica (-4,23±1,95 vs. 2,34±1,39mmHg, p=0,05), na concentração de insulina (-5,11±1,93 vs. -0,65±1,28U/mL, p=0,07) e no HOMA-IR (-1,15±0,49 vs. -0,08±0,33, p=0,09). Durante o período do estudo, as modificações na adiposidade corporal total e central apresentaram correlação significativa com as variações nos parâmetros de gravidade da AOS; na PA sistólica e diastólica; nas concentrações de insulina e no HOMA-IR, mesmo após ajuste para fatores de confundimento. As modificações na adiposidade corporal central apresentaram associação significativa com as variações nas concentrações de noradrenalina e adiponectina. As modificações nos parâmetros de gravidade da AOS apresentaram associação significativa com as variações nas concentrações séricas da proteína C reativa. Este estudo sugere que em pacientes obesos com AOS a restrição energética moderada é capaz de reduzir a adiposidade corporal total e central, os parâmetros de avaliação da gravidade da AOS e a atividade do sistema nervoso simpático.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:54:12Z No. of bitstreams: 1 Carlos Roberto Moraes de Andrade Junior Tese completa.pdf: 804875 bytes, checksum: 953621341dc06525874f609d761ea2b5 (MD5) Made available in DSpace on 2021-01-06T20:54:12Z (GMT). No. of bitstreams: 1 Carlos Roberto Moraes de Andrade Junior Tese completa.pdf: 804875 bytes, checksum: 953621341dc06525874f609d761ea2b5 (MD5) Previous issue date: 2014-03-20 Patients with type 1 diabetes mellitus (T1DM) have an early and diffuse preclinical atherosclerosis process. This process contributes to the high incidence of cardiovascular disease (CVD) found in this population. There are no recommendations for the identification and stratification of patients with T1DM and increased CVD risk. The measurement of the intima and media thickness (IMT) of the common carotid artery correlates with pre-clinical atherosclerosis and CVD risk. Identification of factors associated with the increase of IMT could contribute to the identification of those patients with higher CVD risk. Moreover, the estimation of "vascular age" (VA) using, could be a useful tool for the stratification of CVD risk. Objectives: evaluate the IMT of patients with T1DM compared to a group of individuals without diabetes. Identify clinical and laboratory factors associated with increased IMT and evaluate if the substitution of CA for the VA would be a useful tool to stratify the CVD risk of patients with T1DM. Methods: A cross-sectional study that evaluated 127 patients with T1DM and 125 control subjects. The IMT was measured using a semi-automated border detection software. VA was estimated in subjects with ≥ 35 years old, using normality tables for IMT. Results: patients with T1DM had higher IMT compared to controls (p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:53:24Z No. of bitstreams: 1 Bruno Miguel Jorge Celoria Tese completa.pdf: 1810355 bytes, checksum: 7b3a42af55510bbfaba8820ddda28938 (MD5) Made available in DSpace on 2021-01-06T20:53:24Z (GMT). No. of bitstreams: 1 Bruno Miguel Jorge Celoria Tese completa.pdf: 1810355 bytes, checksum: 7b3a42af55510bbfaba8820ddda28938 (MD5) Previous issue date: 2013-07-22 A diponectin, a hormone produced by adipose tissue, acts regulating energy metabolism and insulin sensitivity. Unlike other adipocytokines, adiponectin has an inverse association with visceral obesity, insulin resistance, type 2 diabetes and cardiovascular disease. Recently, many studies have been demonstrating the effects of genetic variants in ADIPOQ gene on the circulating levels of adiponectin, blood pressure values, risk of non-alcoholic steatohepatitis and type 2 diabetes, and the emergence of obese phenotype. However, most of the results are controversial and have been related to studies conducted in Caucasian and Asian populations. The aim of the present study was to evaluate, in a multiethnic adult population of the metropolitan region of Rio de Janeiro, the possible effects of the genetic variants (-11391 G>A, -11377C>G, +45T>G e T517G) in ADIPOQ gene on the obese phenotype, circulating levels of adiponectin and high sensitivity and quantitative C-reactive protein, and cardiometabolic risk factors. We evaluated 100 lean individuals (BMI 18,5 24,9 kg/m2, age: 32,5 + 9,8 years) and 100 obese individuals (BMI 30 58,2 kg/m2, age 37,5 + 14,1 years), equally distributed men and women. The obese subjects showed high levels of abdominal circunference, blood pressure, fasting glucose, triglycerides, LDL-cholesterol, leptin, insulin, HOMA-IR and C-reactive protein, and exhibited lower levels of HDL-cholesterol and adiponectin, when compared to euthrophic individuals. Correlation analysis showed an inverse relationship between adiponectin and abdominal circumference, insulin, HOMA-IR and blood pressure, and a positive correlation with HDL-cholesterol. Stepwise regression analysis revealed that gender, abdominal circumference, HOMA-IR and the -11391G>A polymorphism were independently related with adiponectin levels. Regarding to the molecular analyses, no association was found between these variants and the obese phenotype. However, the subjects carrying the -11391G>A polymorphism showed lower values of waist to hip ratio, glucose and blood pressure, and higher levels of adiponectin, when compared to wild subjects. Furthermore, the subjects carrying the -11377 C>G polymorphism demonstrated lower levels of systolic, diastolic and mean blood pressure. The results of our study have shown that adiponectin levels differ between lean and obese individuals and that lower levels of this adipocytokine are associated with a worse cardiometabolic profile. Genetic variants in ADIPOQ gene may interfere in this relationship. We conclude that the polymorphisms -11391G>A and -11377 C>G may predict outcome of cardiovascular risk. A adiponectina, um hormônio produzido pelo tecido adiposo, atua na regulação do metabolismo energético e interfere favoravelmente na sensibilidade à insulina através de suas ações no fígado e musculatura esquelética. Ao contrário da maioria das outras adipocitocinas, associa-se inversamente com a obesidade visceral, resistência à insulina, diabetes tipo 2 e doença cardiovascular. Inúmeros estudos demonstraram nos últimos anos os efeitos de variantes genéticas no gene ADIPOQ sobre os níveis circulantes de adiponectina, resistência à insulina, diabetes e obesidade. Entretanto, além de resultados contraditórios, a maior parte desses estudos foi realizada em populações Caucasianas e Asiáticas. Avaliar, em uma população multiétnica adulta do município do Rio de Janeiro, as possíveis associações das variantes genéticas (-11391 G>A, -11377C>G, +45T>G e T517G) no gene ADIPOQ com o fenótipo obeso, níveis circulantes de adiponectina de alto peso molecular e fatores de risco cardiometabólico. Trata-se de um estudo transversal. Foram estudados 100 indivíduos eutróficos (IMC 18,5 24,9 kg/m2, idade: 32,5 + 9,8 anos) e 100 obesos (IMC 30 58,2 kg/m2, idade 37,5 + 14,1 anos), igualmente divididos entre homens e mulheres. Os indivíduos obesos apresentaram valores significativamente maiores de circunferência abdominal, pressão arterial sistólica, diastólica e média, glicemia de jejum, triglicerídeos, LDL-colesterol, leptina, insulina, HOMA-IR e proteína C reativa, quando comparados aos eutróficos. Contrariamente, exibiram menores valores de adiponectina e HDL-colesterol. Análises de correlação mostraram relação inversa e significativa entre a adiponectina, circunferência abdominal, insulina, HOMA-IR e pressão arterial. Com os níveis de HDL-colesterol, a correlação foi positiva. Por meio de análise de regressão múltipla foi possível identificar os determinantes dos níveis séricos de adiponecinta. Sexo masculino, circunferência abdominal, HOMA-IR e a variante genética -11391G>A, foram os principais responsáveis por essa variação, com um R2 de 30%. Quanto à análise genética, não encontramos nenhuma associação entre essas variantes e o fenótipo obeso. Entretanto, os indivíduos carreadores do alelo mutante -11391A apresentaram menores valores de glicemia, pressão arterial e relação cintura-quadril e maiores concentrações sanguíneas de adiponectina, quando comparados aos indivíduos ditos selvagens. Ademais, os carreadores do alelo mutante -11377G apresentaram menores valores de pressão arterial sistólica, diastólica e média. Os resultados do presente estudo demonstram que níveis de adiponectina diferem entre eutróficos e obesos e que concentrações mais baixas dessa adipocitocina estão associadas a um pior perfil cardiometabólico. Variantes no gene ADIPOQ podem interferir nessa relação e alguns polimorfismos parecem ter um perfil protetor no risco cardiovascular.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:41:31Z No. of bitstreams: 1 dissertacao_NADIA_AMORIM_final.pdf: 4927313 bytes, checksum: 936091c55320c87d10d07f806125a3c6 (MD5) Made available in DSpace on 2021-01-05T19:41:31Z (GMT). No. of bitstreams: 1 dissertacao_NADIA_AMORIM_final.pdf: 4927313 bytes, checksum: 936091c55320c87d10d07f806125a3c6 (MD5) Previous issue date: 2013-06-21 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Obstructive sleep apnea (OSA) is considered an independent risk factor for cardiovascular disease. There is evidence that individuals with OSA may have increased inflammatory mediators, changes in the metabolic profile, increased sympathetic activity with consequent elevation of blood pressure (BP) and endothelial dysfunction. Resistant hypertension (RH) is defined as uncontrolled blood pressure (BP ≥ 140/90mmHg) despite the current use of three hypotensive drugs at full doses, including a diuretic, or the need for >3 medications to control BP. OSA has been reported as the most common secondary cause of high blood pressure maintenance. The objective was to determine the prevalence of OSA and verify its association with endothelial function and anthropometric parameters in patients with resistant hypertension (RHGroup) and BP controlled by medication (CHGroup). It was a cross-sectional study involving 40 hypertensive patients (20 in RHG and 20 in CHG), aged between 18 and 75 years. Endothelial function and OSA were assessed by peripheral arterial tonometry. BP was measured by oscillometric method on automatic device. Endothelial function was assessed by peripheral arterial tonometry (PAT) by EndoPAT2000 and the OSA diagnosis also through PAT, using the portable device WatchPAT200. Anthropometric evaluation was performed through measurements of waist (WaC), hip and neck circumference (NC), BMI, waist to height ratio (WHtR), and body composition assessed by bioelectrical impedance. Patients were generally late middle-aged (54.95 ± 2.39 in the RH group and 56.15 ± 2.42 in the controlled hypertension [CH] group. The prevalence of OSA in RHG was 85% (17 of 20) [apnea-hypopnea index=12.39±1.89], and 80% (16 of 20) in CHG (AHI=20.74±4.69) and it was more frequent in men (93.7% [15 of 16] vs 75% [16 of 24]; p=0.04, OR=3.86; 95% IC 0.99 to 14.92). Both groups presented similar anthropometric parameters values. Endothelial function evaluated by reactive hyperemia index was similar in both groups (RHG: 1.88±0.09 vs CHG: 2.03±0.09; p=0.28). Although we found differences in oxygen desaturation> 4% (RHG: 28.75 ± 5.08 vs CHG: 64.15 ± 16.97, p = 0.04), total sleep time (RHG: 309.5 ± 15.27 vs CHG: 323.3 ± 18.74 min) and minimum saturation (RHG: 87.8±0.85 vs CHG: 83.3±2.37%) was not different. In general, OSA was correlated with weight (r = 0.51, p = 0.0007), BMI (r = 0.41, p = 0.0078), WaC (r = 0, 44, p = 0.005), NC (r = 0.38, p = 0.01) and WHtR (r = 0.39, p = 0.01) and independently associated with impairment of endothelial function (p = 0.0297, OR = 0.17, 95% CI 0.04 to 0.72). In conclusion, the findings of this study show high prevalence of OSA in patients with resistant hypertension, similar to that of controlled hypertension group. There were no significant differences in endothelial function between resistant and controlled hypertension patients. The presence of OSA in the total group of hypertensive patients was associated with increased risk of impaired endothelial function. A apneia obstrutiva do sono (AOS) é considerada um fator de risco independente para as doenças cardiovasculares. Existem evidências de que indivíduos com apneia obstrutiva do sono podem apresentar elevação nos mediadores inflamatórios, alterações no perfil metabólico, aumento na atividade do sistema nervoso simpático, com consequente elevação da pressão arterial e disfunção endotelial. Nos últimos anos, inúmeros estudos tem apontado a AOS como um dos fatores responsáveis pela hipertensão resistente. O objetivo do estudo foi avaliar a presença da apneia obstrutiva do sono e o comportamento da função endotelial em pacientes com hipertensão resistente, comparando com hipertensos apresentando pressão arterial controlada com até 3 classes diferentes de fármacos anti-hipertensivos. Trata-se de um estudo transversal com 40 pacientes hipertensos: 20 com hipertensão arterial resistente (HAR) e 20 com pressão arterial controlada por medicação (hipertensão arterial controlada; HAC), sem distinção de raça ou gênero, com idade entre 18 e 75 anos. A pressão arterial casual e a monitorização ambulatorial da pressão arterial foram aferidas por método oscilométrico em aparelhos automáticos. A função endotelial e a presença da apneia obstrutiva do sono foram avaliadas através da tonometria arterial periférica pelos equipamentos Endo-PAT2000® e o aparelho portátil Watch-PAT200®, respectivamente. A avaliação antropométrica foi realizada através das aferições das circunferências da cintura e do pescoço, índice de massa corporal (IMC), e relação cintura-estatura. A composição corporal foi avaliada por bioimpedância elétrica BIODYNAMICS® 450. As análises estatísticas foram realizadas pelo software GraphPad PRISM, versão 6.01. A prevalência de AOS no grupo com HAR foi de 85% (Índice de apneia-hipopneia [AHI]= 12,39±1,89) e de 80% no grupo com HAC (AHI =20,74±4,69), sendo mais frequente em homens (p=0,04; OR=3,86; 95% IC 0,99 a 14,52). Os dois grupos apresentaram valores semelhantes das variáveis antropométricas avaliadas. A função endotelial avaliada pelo índice de hiperemia reativa foi similar nos dois grupos (grupo HAR: 1,88±0,09 vs. grupo HAC: 2,03±0,09; p=0,28). Apesar do número de dessaturações de oxigênio >4% ter apresentado diferença significativa entre os grupos (grupo HAR: 28,75±5,08 vs. grupo HAC: 64,15±16,97; p=0,04), o tempo total de sono (grupo HAR: 309,5±15,27 vs. grupo HAC: 323,3±18,74 min) e a saturação mínima da oxi-hemoglobina (grupo HAR: 87,8±0,85 vs. grupo HAC: 83,3±2,37%) não mostraram essa diferença. Considerando todos os pacientes hipertensos, o AHI apresentou correlação significativa com o peso corporal (r=0,51; p=0,0007), o IMC (r=0,41; p=0,007), a circunferência da cintura (r=0,44; p=0,005), a circunferência do pescoço (r=0,38; p=0,01) e a relação cintura-estatura (r=0,39; p=0,01). Os pacientes sem AOS em comparação com os pacientes com AOS, apresentaram risco significativamente menor de apresentar comprometimento da função endotelial (OR=0,17; 95% IC 0,04-0,72; p=0,03). Os achados do presente estudo sugerem que a prevalência de AOS em pacientes com hipertensão resistente é elevada, porém semelhante a de indivíduos com hipertensão controlada. Pacientes com hipertensão resistente e controlada não apresentaram diferenças significativas em relação à função endotelial. A gravidade de AOS no grupo total de hipertensos se associou com maior risco de comprometimento da função endotelial.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:53:57Z No. of bitstreams: 1 Livia de Paula Nogueira Tese completa.pdf: 1982287 bytes, checksum: 49c9d2991dcba7fd97f90fb58127091f (MD5) Made available in DSpace on 2021-01-06T20:53:57Z (GMT). No. of bitstreams: 1 Livia de Paula Nogueira Tese completa.pdf: 1982287 bytes, checksum: 49c9d2991dcba7fd97f90fb58127091f (MD5) Previous issue date: 2013-04-25 Conselho Nacional de Desenvolvimento Científico e Tecnológico Cardiovascular diseases are the leading cause of mortality in Western countries. Some studies have suggested that green tea has beneficial effects on different cardiovascular risk factors. However, others have failed to show such an association. Objective to evaluate the effects of green tea on blood pressure, endothelial function, metabolic profile, inflammatory activity and body adiposity in obese pre-hypertensive women. Study clinical, randomized, crossover, double-blinded, placebo-controlled. During 4 weeks women were instructed to ingest 3 capsules of green tea extract per day (500mg green tea extract/capsule), after 2 weeks of washout and then ingested placebo for 4 weeks. The women who began the study with placebo later have used green tea. That is, all patients received placebo and green tea for the same period. At the beginning and end of each treatment the variables were analyzed. Study of 20 women with pre-hypertension, obesity grade I and II, aged between 25 and 59 years. Study site in Laboratory of the Discipline of Clinical and Experimental Pathophysiological Clinex. Rio de Janeiro State University. Variables studied was blood pressure, reactive hyperemia index (evaluated with Endo-PAT2000®), C-reactive protein, interleukin 6, tumor necrosis factor alpha, vascular cell adhesion molecule, intercellular adhesion molecule, plasminogen activator inhibitor-1, vascular endothelial growth factor, E-selectin, adiponectin, total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, triglycerides, blood glucose, insulin, HOMA, body mass index, waist circumference, hip circumference, waist-to-hip ratio and body fat. As results, in the assessment of blood pressure by ambulatory blood pressure monitoring was observed significant reduction in 24 hours systolic blood pressure (pre 130.3±1.7 mmHg vs. post 127.0±2.0 mmHg; p= 0.02), daytime systolic blood pressure (pre 134.0±1.7 mmHg vs. post 130.7±2.0 mmHg; p= 0.04) and nighttime systolic blood pressure (pre 122.2±1.8 mmHg vs. post 118.4±2.2 mmHg; p= 0.02), after consumption of green tea compared with placebo. After consumption of green tea, there was an increase, although not statistically significant, in reactive hyperemia index (pre 1.98±0.10 vs. post 2.22±0.14), besides expressive reduction in the concentration of intercellular adhesion molecule (pre 91.8±8.0 ng/ml vs. post 85.8±5.6 ng/ml) and vascular endothelial growth factor (pre 195.8±46.2 pg/ml vs. post 158.6±38.7 pg/ml), however without statistical significance. The other variables evaluated did not change significantly after consumption of green tea. A strong correlation was observed between reduction in 24 hours systolic blood pressure and 24 hours diastolic blood pressure, assessed by ambulatory blood pressure monitoring, and the increase of reactive hyperthermia index (r= -0.47; r= -0.50, respectively). The results of this study suggest that green tea has a beneficial effect on blood pressure and possibly on endothelial function. As doenças cardiovasculares são a principal causa de morte nos países ocidentais. Alguns estudos sugerem que o chá verde tem efeito benéfico sobre diferentes fatores de risco cardiovascular. No entanto, outros estudos não mostraram essa associação. Objetiva avaliar em mulheres pré-hipertensas obesas o efeito do consumo de chá verde sobre: a pressão arterial, a função endotelial, o perfil metabólico, a atividade inflamatória e a adiposidade corporal. Estudos clínico, randomizado, cruzado, duplo-cego e placebo-controlado. Durante 4 semanas as mulheres foram orientadas a ingerir 3 cápsulas de extrato de chá verde por dia (500mg extrato chá verde/cápsula) passando por 2 semanas de washout e posteriormente ingeriam por mais 4 semanas o placebo. As mulheres que iniciaram o estudo tomando placebo posteriormente utilizaram o chá verde. Ou seja, todas as pacientes receberam chá verde e placebo por um mesmo período. No início e final de cada tratamento foram analisadas as variáveis. Foram avaliadas 20 mulheres pré-hipertensas, obesidade grau I e II, idade entre 25 e 59 anos. O local do estudo foi o Laboratório da Disciplina de Fisiopatologia Clínica e Experimental Clinex. Universidade do Estado do Rio de Janeiro. As variáveis estudadas foram a pressão arterial, índice de hipertemia reativa (avaliada com Endo-PAT2000®), proteína C reativa, interleucina-6, fator de necrose tumoral-α, molécula de adesão intercelular e molécula de adesão vascular celular, inibidor de ativador do plasminogênio, fator de crescimento endotelial vascular, E-selectina, adiponectina, colesterol total, LDL-colesterol, HDL-colesterol, triglicérides, glicemia, insulina, HOMA, índice de massa corporal, circunferência de cintura, circunferência de quadril, relação cintura quadril e percentual de gordura corporal. Como resultados, na avaliação da pressão arterial pela monitorização ambulatorial da pressão arterial, observou-se redução significativa da pressão arterial sistólica de 24 horas (pré 130,3±1,7 mmHg vs. pós 127,0±2,0 mmHg; p= 0,02), pressão arterial sistólica diurna (pré 134,0±1,7 mmHg vs. pós 130,7±2,0 mmHg; p= 0,04) e pressão arterial sistólica noturna (pré 122,2±1,8 mmHg vs. pós 118,4±2,2 mmHg; p= 0,02), após o consumo do chá verde, em comparação ao uso do placebo. Após o consumo do chá verde foi observado aumento, embora estatisticamente não significativo, no índice de hiperemia reativa (pré 1,98±0,10 vs. pós 2,22±0,14), além de redução expressiva na concentração da molécula de adesão intercelular (pré 91,8±8,0 ng/ml vs. pós 85,8±5,6 ng/ml) e do fator de crescimento endotelial vascular (pré 195,8±46,2 pg/ml vs. pós 158,6±38,7 pg/ml), porém sem significância estatística. As demais variáveis avaliadas não se modificaram de forma significativa após o consumo do chá verde, em comparação ao placebo. Foi observada forte correlação entre redução de pressão arterial sistólica e diastólica de 24hs, avaliada pela monitorização ambulatorial da pressão arterial, e o aumento do índice de hipertemia reativa (r= -0,47; r= -0,50, respectivamente). Os resultados do presente estudo sugerem que o chá verde tem efeito benéfico sobre a pressão arterial e possivelmente sobre a função endotelial.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:53:12Z No. of bitstreams: 1 Tese_Final_Priscila Alves Maranhao.pdf: 1258682 bytes, checksum: 84ec9b1ac404b329ff94e92fe884e536 (MD5) Made available in DSpace on 2021-01-06T20:53:12Z (GMT). No. of bitstreams: 1 Tese_Final_Priscila Alves Maranhao.pdf: 1258682 bytes, checksum: 84ec9b1ac404b329ff94e92fe884e536 (MD5) Previous issue date: 2013-04-24 Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro Changes in eating habits have caused striking effects on public health, directly related to increased intake of food rich in fat, mainly saturated fat. The main consequence of this consumption is the excessive and prolonged state of postprandial lipemia (PPL), considered one an important factor related to metabolic abnormalities and vascular damage. The aim of this study was to assess effects of fat overload on microvascular reactivity in obese women. Of the 41 study participants, 21 had the diagnosis of obesity, with BMI of 32.4 ± 1.6 kg/m2 (mean ± SD) and age of 31.6 ± 5 years and 20 healthy women with BMI of 21.9 ± 1.7 kg/m2and age 27.2 ± 5.5 years. After clinical and laboratorial assessment, participants had the microcirculation examined by two methods: dynamic, using the nailfold bed to assess functional capillary density (FCD), red blood cell velocity in in control conditions (RBCV) and peak (RBCVmax) and time (TRBCVmax) to reach it after 1 min arterial occlusion. The second technique was the finger dorsum to assess FCD at rest and during the reactive hyperemia response and after venous occlusion. Blood sampling was performed to determine total cholesterol (TC), triglycerides (TG), HDL- c and free fatty acids (FFA), glucose, insulin and plasma viscosity at 30 and 50 rotations per minute (rpm). Systolic (SBP) and diastolic (DBP) blood pressures and heart rate (HR) were also measured. After these measurements at rest, all participants received a meal rich in lipids, and after 30, 60, 120 and 180 min after ingestion, videocapillaroscopy exams and blood samples were taken again. Results - Obese participants, after fat overload, presented significantly lower values than at rest at finger dorsum of FCD (p = 0.02), FCD during reactive hyperemia (p = 0.02) and post- venous occlusion (p = 0.02), HDL-C (p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:37:04Z No. of bitstreams: 1 TESE_FINAL_PUBLICADA_Ana_Rosa_da_Cunha_Machado.pdf: 4164997 bytes, checksum: f8da8c5619c255cc0063d304044f1ad8 (MD5) Made available in DSpace on 2021-01-05T19:37:04Z (GMT). No. of bitstreams: 1 TESE_FINAL_PUBLICADA_Ana_Rosa_da_Cunha_Machado.pdf: 4164997 bytes, checksum: f8da8c5619c255cc0063d304044f1ad8 (MD5) Previous issue date: 2012-11-06 Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro Magnesium has been the subject of some studies on the pathogenesis of hypertension for having significant inverse correlation between its serum levels and the incidence of cardiovascular disease. The main objective of this study was to evaluate the effects of magnesium supplementation on vascular function in hypertensive patients in use of hydrochlorothiazide. Furthermore, serum and intracellular magnesium were correlated with nutritional parameters, blood pressure, metabolic, structural and functional aspects of the macro- and microcirculation. Hypertensive women, 40 to 65 years-old, in use of hydrochlorothiazide in the past 4 weeks, were selected for this project. Initially we conducted a cross-sectional study to assess the associations of low serum (

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:41:01Z No. of bitstreams: 1 Thais da Silva Ferreira.pdf: 1721138 bytes, checksum: 357b5ddb0d865e2c956be91073fce1fa (MD5) Made available in DSpace on 2021-01-05T19:41:01Z (GMT). No. of bitstreams: 1 Thais da Silva Ferreira.pdf: 1721138 bytes, checksum: 357b5ddb0d865e2c956be91073fce1fa (MD5) Previous issue date: 2012-06-19 The inverse association between dietary calcium intake and body adiposity and blood pressure is established in epidemiological studies. Experimental data suggest that it may be mediated by alterations in intracellular calcium concentration ([Ca]i). There are few studies evaluating the relationship beween dietary calcium and [Ca]i. The objective of the present study was to evaluat the association of dietary calcium with [Ca]I, body adiposity, metabolic profile, inflammatory biomarkers, blood pressure, and endothelial function in women. It was conducted an observational and cross-sectional clinical trial, including 76 women with pre-menopausal status who were submitted to the following evaluations: dietary intake (by a food frequency questionnaire); [Ca]I in erythrocytes (by atomic absorption spectrometry); body adiposity (by body mass index [BMI] and electrical bioimpedance; abdominal adiposity (by waist circumference and waist-to-hip-ratio; metabolic profile (by assessing plasma glucose, total cholesterol and fractions, insulin and HOMA-IR); inflammatory biomarkers (adiponectin and C-reactive protein); endothelial function (by analyzing adhesion molecules and by peripheral artery tonometry [PAT]); and blood pressure. Calcitriol, parathyroid hormone, and serum and urinary calcium completed calcium metabolism. Participants were stratified into two groups according to their mean usual dietary calcium intake: low calcium group (LCG; n=32; dietary calcium intake

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:53:06Z No. of bitstreams: 1 Sergio Emanuel Kaiser.pdf: 1530841 bytes, checksum: 92e8b80b17726b318ac5e8dbff0fcc88 (MD5) Made available in DSpace on 2021-01-06T20:53:06Z (GMT). No. of bitstreams: 1 Sergio Emanuel Kaiser.pdf: 1530841 bytes, checksum: 92e8b80b17726b318ac5e8dbff0fcc88 (MD5) Previous issue date: 2012-04-17 Capillary rarefaction and microcirculatory endothelial dysfunction are hallmarks of hypertension, rendering patients vulnerable to target organ lesions. The study aimed at assessing the effect of a six-month treatment period upon capillary density and microvascular reactivity to physiological and pharmacological stimuli. In addition, two different treatment strategies were tested for possible differences between effects upon those variables. A total of 44 patients were recruited, mean age 46.7±1.3 years and 20 normotensive individuals served as controls, mean age 48.0±1.6 years. Anthropometrical and laboratory data were collected, as well as plasma levels of vascular endothelial growth factor (VEGF), its receptor Flt-1 and nitric oxide (NO). Capillary density was obtained by intra-vital microscopy of the dorsum of the middle phalanx before and after post-occlusive reactive hyperemia (PORH). Capillary loops were counted by a semi-automated software. Microvascular reactivity was tested by laser Doppler flowmetry (LDF), and the challenges consisted of acetylcholine iontophoresis, local thermal hyperemia (LTH) and PORH. Patients were randomly allocated to either one of two treatment arms: metoprolol succinate uptitrated to 100 mg daily or olmesartan medoxomil uptitrated to 40 mg daily, with addition of hydrochlorothiazide if necessary. Controls underwent the same initial protocol and all tests were repeated in patients after six months. Baseline clinical and laboratory parameters were similar between patients and controls and between the two treatment groups. After six months there were slight, although significant, differences between the two groups in waist/hip ratio and HDL-cholesterol. In the whole cohort, pretreatment capillary density was significantly reduced compared to controls (71.3±1.5 vs 80.6±1.8 cap/mm2 p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:57:36Z No. of bitstreams: 1 Jessica Lopes Nobre Dissertacao completa.pdf: 868246 bytes, checksum: 8bc31f54c2aa25aa925ac174d1381ecb (MD5) Made available in DSpace on 2021-01-06T20:57:36Z (GMT). No. of bitstreams: 1 Jessica Lopes Nobre Dissertacao completa.pdf: 868246 bytes, checksum: 8bc31f54c2aa25aa925ac174d1381ecb (MD5) Previous issue date: 2011-07-04 Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro Calcium influences energy metabolism regulation and causes body weight loss. Since early weaning and maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance and others endocrine dysfunctions, we studied the possible effect of dietary calcium supplementation on endocrine dysfunctions in these two experimental model of obesity: 1) Early Weaning (EW): lactating rats were involved with a bandage to interrupt the lactation during the last 3 days of standard lactation, and C (control) - dams whose pups had free access to milk during all lactation (21 days). 2) Maternal nicotine exposure (N): Two days after birth, it was implanted on the mothers, osmotic minipumps containing nicotine solution (6 mg/Kg/day, 14 days) or saline (C) in the same condition. At 120 days-old, all offspring received dietary calcium supplementation (10g of calcium carbonate/Kg of rat chow) or standard diet. Rats were killed at 180 days-old. Significant data were p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:36:14Z No. of bitstreams: 1 Adriana Burla Klajman Tese completa.pdf: 1316186 bytes, checksum: 460b096f78aa4f8100f9f390bc283f00 (MD5) Made available in DSpace on 2021-01-05T19:36:14Z (GMT). No. of bitstreams: 1 Adriana Burla Klajman Tese completa.pdf: 1316186 bytes, checksum: 460b096f78aa4f8100f9f390bc283f00 (MD5) Previous issue date: 2011-06-03 Many evidences show that obesity is associated to structural and functional changes in the heart of human and animal models. Recent studies also show that human obesity is associated with vascular structural and functional modifications, specially at large and medium-sized arteries. Epidemiological studies have confirmed that obesity is a significant risk factor for the development of proteinuria and end-stage renal disease in a normal population. With the objective to determinate morphological changes related to cardiac, vascular and renal remodeling in an experimental model of monosodium glutamate (MSG)-induced obesity and the effect of metformin at this finding. Twenty five rats were studied and divided into five groups: control with 16 e 22 weeks (CON-16 and CON-22); obese with 16 and 22 weeks (MSG-16 e MSG-22), and obese + metformin (MET-22) 300mg/Kg/day per oral. The characterization of insulin resistance was done through measurement of plasma insulin and calculation of HOMA-IR index. The morphological analysis and the quantification of myocardial collagen were carried out by Image Pro Plus analysis system. The systolic blood pressure was slightly higher in MSG-22 group, reaching statistical significance when compared to MSG-16 group (122±2 vs 108±2 mmHg, p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T18:07:36Z No. of bitstreams: 1 Daniel Arthur Barata Kasal Tese Completa.pdf: 8208147 bytes, checksum: 6b47779d5f20a445260f2fcfd9b7b78c (MD5) Made available in DSpace on 2021-01-05T18:07:36Z (GMT). No. of bitstreams: 1 Daniel Arthur Barata Kasal Tese Completa.pdf: 8208147 bytes, checksum: 6b47779d5f20a445260f2fcfd9b7b78c (MD5) Previous issue date: 2011-02-16 Angiotensin (Ang) II and aldosterone (aldo) induce hypertension through mechanisms in part mediated by adaptive immunity and T responder lymphocytes. T regulatory (Treg) lymphocytes suppress pro-inflammatory mediators of the immune system. We questioned whether Treg adoptive transfer will blunt Ang II or aldo-induced hypertension and vascular injury, by evaluating two distinct protocols. In the Ang II protocol, male C57BL/6 mice were injected i.v. with Treg or T responder cells, and then infused with Ang II (1μg/kg/min) or saline, for 14 days. In the aldosterone protocol, another set of animals was injected with Treg or T responder cells, and then infused with aldosterone (600μg/kg/d) or saline, for the same period. The aldosterone group received saline 1% in drinking water. Both Ang II and aldosterone treated mice presented an increase in systolic blood pressure (43% and 31% respectively), of NADPH oxidase activity in aorta (1.5 and 1.9 fold, respectively) and heart (1.8 and 2.4 fold respectively) and an impaired vasodilatory response do acetylcholine (by 70% and 56% respectively), when compared to their controls (P

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:36:06Z No. of bitstreams: 1 Wille Oigman Completa.pdf: 2467523 bytes, checksum: 3411c8296f76145a764796a2120be64d (MD5) Made available in DSpace on 2021-01-05T19:36:06Z (GMT). No. of bitstreams: 1 Wille Oigman Completa.pdf: 2467523 bytes, checksum: 3411c8296f76145a764796a2120be64d (MD5) Previous issue date: 2010-11-22 The rate of control of hypertension remains suboptimal despite widespread educational programs and the increasing number of novel medications. The combination of drugs with different mechanism of action has become an alternative to improve blood pressure reduction and control, enhance adherence to the treatment and reduce adverse events. This randomized 4X4 factorial study determined the efficacy and safety of telmisartan (T) plus amlodipine (A) in hypertensive patients. Adults (N=1461) with stage 1 or 2 hypertension (baseline blood pressure (BP) 153.2±12.1 ⁄101.7±4.3 mm Hg) were randomized to 1 of 16 treatment groups with T 0, 20, 40, 80 mg and A 0, 2.5, 5, 10 mg for 8 weeks. The greatest leastsquare mean systolic ⁄ diastolic BP reductions were observed with T80 mg plus A10 mg (- 26.4 ⁄20.1 mm Hg; P90% with this combination. Peripheral edema was most common in the A10-mg group (17.8%); however, this rate was notably lower when A was used in combination with T: 11.4% (T20 ⁄ A10), 6.2% (T40 ⁄ A10), and 11.3% (T80 ⁄ A10). Ambulatory BP monitoring (ABPM) was performed, at baseline and after 8 weeks of treatment; the endpoints of interest were the changes from baseline in 24-hour systolic and diastolic BP. Mean reductions from baseline in 24-hour BP for the combination of the highest doses of telmisartan 80 mg and amlodipine 10 mg were -22.4/-14.6 mmHg versus -11.9/-6.9 mmHg for amlodipine 10 mg and -11.0/-6.9 mmHg for telmisartan 80 mg (p< 0.001 for each comparison. This study also presents most of the relevant results in hypertensive patients and a post hoc analysis of subgroups including elderly, diabetics type 2, systolic hypertension and obese patients. These findings demonstrate that telmisartan and amlodipine in combination provide substantial 24 hour BP efficacy that is superior to either monotherapy in patients with stages 1 and 2 hypertension. A taxa de controle da hipertensão arterial permanece subótima apesar dos amplos e intensos programas institucionais e o número das novas medicações. A combinação de drogas de diferentes mecanismos de ação vem se tornando uma alternativa para aumentar a redução na pressão arterial (PA) e aumentar seu controle, aumentar aderência ao tratamento e reduzir os eventos adversos. Um estudo fatorial 4X4 foi desenhado para determinar a eficácia e a segurança de telmisartana (T) mais anlodipino (A) em pacientes hipertensos estágios I e II. Pacientes hipertensos adultos (N=1461) estágios I e II (pressão arterial basal 153,2±12,1 ⁄101,7±4,3 mm Hg) foram randomizados para 1 de 16 grupos de tratamento com T 0, 20, 40, 80 mg e A 0, 2.5, 5, 10 mg por oito semanas. A maior redução na média das pressões sistólica e diastólica foram observadas com T 80 mg mais A10 mg (- 26,4 ⁄20,1 mm Hg; p90% com esta combinação. O edema periférico maleolar foi o evento adverso mais frequente e ocorreu no grupo A 10mg (17,8%), porém, esta taxa foi marcadamente menor quando A foi usada associada com T: 11,4% (T20+A10), 6,2% (T40+ A10), e 11,3% (T80+A10). Um subestudo utilizando a monitorização ambulatorial da pressão arterial (MAPA) foi realizado na fase basal e após oito semanas de tratamento. A maior redução média das pressões nas 24 horas a partir do período basal foi registrada para a combinação de telmisartana 80 mg e anlodipino 10 mg e encontrou-se queda de 22,4/14,6 mmHg, de 11,9/6,9 mmHg para anlodipino 10 mg monoterapia e de 11,0/6,9 mmHg para telmisartana 80 mg (p< 0,001). Além disso, resultados relevantes foram também constatados numa análise post hoc de subgrupos incluindo idosos, obesos, diabéticos tipo 2 e hipertensão sistólica. A resposta anti-hipertensiva da combinação foi semelhante, independente de qualquer característica de cada subgrupo. Estes dados demonstram que telmisartana e anlodipino em combinação oferecem substancial redução e controle nas 24 horas superior às respectivas monoterapias em hipertensos estágios I e II.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:37:40Z No. of bitstreams: 1 MARILIA DUARTE BRANDAO PANICO.pdf: 8803314 bytes, checksum: a11a097b85ebfe5536636b455e8a4cb3 (MD5) Made available in DSpace on 2021-01-05T19:37:40Z (GMT). No. of bitstreams: 1 MARILIA DUARTE BRANDAO PANICO.pdf: 8803314 bytes, checksum: a11a097b85ebfe5536636b455e8a4cb3 (MD5) Previous issue date: 2010-07-05 Peripheral Artery (DAP) is the result of the atherosclerotic process involving the arteries of the superior and inferior limbs, abdominal aorta and its visceral branches. The objective was detect PAD, using the ankle brachial index (ABI), in patients ≥ 30 years old attended in the Unidade Docente - Assistencial of Angiology (UDA), correlating it with risk factors (RF) and estimated glomerular filtration rate (eGFR), with intention to describe the RF and association with chronic kidney disease. It was used a standard questionnaire and the ABI to identify patients with and without PAD. Laboratorial tests, as total cholesterol, triglycerides, HDL-c, LDL-c, glycemia, creatinine and homocysteine were correlated to ABI. Statistical analyses were done using the Statistical Package for the Social Sciences (SPSS) 16.0 program. The results had pointed to the importance of the ABI in the diagnosis of PAD, with degrees of mild, discrete, moderate and serious stenosis for the symptomatic patients, and the identification of the asymptomatic ones, making possible intervention in the RF and control of their complications. Tabagism was confirmed as the RF with most important odds ratio for PAD. The systolic and diastolic hypertension showed to be more significant than diabetes mellitus, as diseases associated to PAD. In laboratorial evaluation, the traditional blood markers for PAD: total cholesterol, triglycerides and glucose had shown statistics significance. Homocysteine was the marker most significant in PAD. Association between reduction of ABI with systolic and diastolic hypertension and glycemias occurred, as well as reduction of the averages of the eGFR. The conclusion was, in patients with PAD, hyperhomocysteinemia and decrease of eGFR are possible of prevention, contributing in the reduction of the morbimortality of PAD. The narrow association of decrease eGFR in patients with PAD represented excellent contribution of this study. A Doença da Artéria Periférica (DAP) é o resultado do processo aterosclerótico das artérias dos membros superiores, inferiores, aorta abdominal e seus ramos viscerais. Nosso objetivo foi detectar a DAP correlacionando-a com fatores de risco (FR) e a filtração glomerular estimada (FGe) nos pacientes com ≥30 anos, assistidos na Unidade docente - assistencial de Angiologia (UDA) do Hospital Universitário Pedro Ernesto da Faculdade de Ciências Médicas - UERJ, com o intuito de descrever os FR e associação com doença renal crônica à DAP, a partir da aferição do índice tornozelo-braço (ITB); determinar a alteração da FGe por equações, relacionando-a à progressão da DAP. Foi usado um questionário padrão e o ITB para identificar os pacientes com e sem DAP. Correlacionou-se as variáveis laboratoriais, como os níveis séricos de colesterol, triglicerídeos, HDL-c, LDL-c, glicemia, homocisteína com a FGe e com o ITB. As análises estatísticas foram feitas pelo programa Statistical Package for the Social Sciences (SPSS) 16.0 Os resultados apontaram para a importância do ITB no diagnóstico da DAP, com configuração de graus de obstrução leve, discreta, moderada e grave para os sintomáticos, e a identificação dos assintomáticos, possibilitando intervenção nos fatores de risco demarcados e o controle de suas complicações. O tabagismo mostou-se como o FR com razão de risco mais importante para DAP. A hipertensão sistólica e a diastólica foram variáveis clínicas mais significativas que o diabetes mellitus. Os marcadores séricos tradicionais para DAP: colesterol total, triglicerídeos e glicemia mostraram significância estatística. A homocisteína foi o marcador mais significativo em relação à DAP. Ocorreu associação entre redução do ITB com a elevação dos níveis pressóricos, das glicemias, da homocisteína, assim como diminuição das médias da FGe. Foi conclído que nos pacientes com DAP a hiperhomocisteinemia está associada à diminuição da FGe, ambas passíveis de prevenção, contribuindo na redução da morbimortalidade da DAP. A estreita associação da DAP com a FGe diminuída representou relevante contribuição do estudo.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:31:43Z No. of bitstreams: 1 Cristina Fajardo Diestel-Tese.pdf: 1613363 bytes, checksum: 52a6d554d1e347c7ea00ee67b6ce2695 (MD5) Made available in DSpace on 2021-01-06T20:31:43Z (GMT). No. of bitstreams: 1 Cristina Fajardo Diestel-Tese.pdf: 1613363 bytes, checksum: 52a6d554d1e347c7ea00ee67b6ce2695 (MD5) Previous issue date: 2010-05-26 Total splenectomy (TS) causes changes in the immune response that increase the risk of development of severe infection. The objective of the present study was to determine the lymphocyte subpopulations in blood, spleen, and splenic auto-implants (SAI) of rats subjected to TS alone or in association with SAI (TS + SAI) and to dietary supplementation with L-glutamine (GLN). Sprague-Dawley rats were subjected to sham surgery, to TS, and to TS + SAI, with SAI retrieved six and 12 weeks after the beginning of the experiment, with and without GLN. Supplementation was provided daily for 15 days preceding the blood collection performed immediately before the surgical procedures (D0), 12 weeks after sham surgery and TS, and six and 12 weeks after TS + SAI. Blood count and flow cytometry were used for the evaluations. Data were analyzed statistically by parametric and nonparametric tests, with the level of significance set at p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:57:14Z No. of bitstreams: 1 Dissertacao-Alessandra S M F da Costa.pdf: 1148687 bytes, checksum: 2d0afb09d4d2095bf76217bd81f403b1 (MD5) Made available in DSpace on 2021-01-06T20:57:14Z (GMT). No. of bitstreams: 1 Dissertacao-Alessandra S M F da Costa.pdf: 1148687 bytes, checksum: 2d0afb09d4d2095bf76217bd81f403b1 (MD5) Previous issue date: 2010-03-03 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Endothelial dysfunction in patients with type 1 diabetes appears to be an early event in the genesis of vascular complications. The purpose of the present study is to assess endothelial function in the microcirculation and arterial stiffness, by comparing with non-diabetic controls, and correlating with clinical, demographic and laboratorial parameters. We evaluated 57 patients with type 1 diabetes aged 32.5 (13-61) years and with a disease duration of 15 (1-48)years, and 53 controls using laser Doppler flowmetry during low-current iontophoresis of acetylcholine (ACh) (endothelium dependent response), post occlusive reactive hyperemia(PORH) and maximum vasodilator function during thermal hyperemia. Endothelium-independent response was measured after iontophoresis of sodium nitroprusside (SNP).The peripheral pressure waveform was analyzed to assess the arterial stiffness. Diabetic patients underwent clinical and laboratory evaluation (smoking, disease duration, daily insulin dose, use of medications that could improve endothelial function such as antihypertensive drugs and statins, blood pressure, body mass index, urinary albumin excretion, lipid profile, glycemic control and C-reactive protein levels-CRP). Mean resting microvascular flux did not differ between control subjects and patients with type 1 diabetes, as well as arterial stiffness assessed through stiffness index and reflection index. Microvascular response to ACh was significantly reduced in patients (p=0,002). However, despite the reduction ofAUC NPS, the analysis with repeated measures disclosed no difference between the groups in relation to the doses (p=0,15). Maximal skin microvascular vasodilation induced by thermal hyperemia was found to be higher in the control group than among patients (93,6(24,5-379-,9) e 56,6(31,5-204,5), respectively p=0,04). On the other hand, during PORH, maximal increase in flux and area under the curve of the hyperemic response did not differ between patients and controls, although the time frame to reach maximum flux and the time to half recovery after hyperemia was longer in patients than in controls (P=0.02) . Uric acid, hba1c, age and CRP were the most important contributing factors to the variation of microvascular reactivity, while disease duration, the diastolic arterial pressure and HDL cholesterol were independently associated to arterial stiffness. Despite the correlation between drugs with hemorheologycal properties and arterial stiffness, the exclusion of patients who were taking such substances did not affect the results. We conclude that in the studied population of type 1 diabetic patients, the endothelium-dependent vascular responses and maximal vasodilator capacity are significantly reduced. In what concerns arterial stiffness, our study disclosed no difference between diabetics and controls. Moreover, Acetylcholine response can be correlated to arterial stiffness in diabetics, and further studies aiming at the evaluation of the micro and macrovascular reactivity should be performed with consumers of drugs which may be likely to affect the endothelial function. A disfunção endotelial tem sido sugerida como evento precoce na patogênese das complicações vasculares do DM1. O presente estudo objetivou avaliar a função endotelial na microcirculação e rigidez arterial no diabetes tipo 1 comparando com controles não diabéticos e correlacionando com variáveis clínicas, demográficas e laboratoriais. Foram avaliados 57 pacientes com diabetes tipo 1 com idade de 32,5 (13-61) anos e duração de doença de 15 (1-48) anos e 53 controles através de fluxometria cutânea por laser-Doppler após iontoforese de Acetilcolina(ACh) (resposta endotélio dependente), hiperemia reativa pós oclusiva(HRPO) e a capacidade máxima de vasodilatação após hiperemia térmica. Já a resposta endotélio independente foi avaliada após iontoforese de Nitroprussiato de sódio (NPS). A rigidez arterial foi mensurada através da análise da onda de pulso digital com os índices de rigidez arterial e de reflexão. Os pacientes diabéticos foram submetidos à avaliação clínica e laboratorial (histórico de tabagismo, dose diária de insulina, duração do diabetes, uso de drogas que alteram a função endotelial como anti-hipertensivos e estatinas, níveis pressóricos, índice de massa corporal, excreção urinária de albumina, perfil lipídico, controle glicêmico e níveis de proteína C-reativa). O fluxo microvascular médio em repouso não foi diferente entre pacientes e controles , assim como a complacência arterial mensurada através do índice de rigidez arterial e do índice de reflexão. A resposta vascular a vasodilatação mediada pela ACh encontrou-se significantemente reduzida nos pacientes (p=0,002). No entanto, apesar da diferença verificada na área abaixo da curva de NPS em relação ao controle, a análise por medidas repetidas não apontou diferença entre os grupos em relação às doses entre os grupos (p=0,15). A vasodilatação cutânea máxima induzida pela hiperemia térmica foi maior entre os controles em comparação com os diabéticos 93,6(24,5-379-,9) e 56,6(31,5-204,5), respectivamente p=0,04. Por outro lado, durante a HRPO, o aumento máximo no fluxo e a área abaixo da resposta hiperêmica não divergiram entre pacientes e controles, embora o tempo para alcançar o fluxo máximo tenha sido maior nos diabéticos do que nos controles(p=0,02). As principais variáveis correlacionadas com a microcirculação foram o ácido úrico, a hemoglobina glicada, a idade e a proteína C reativa, e com a rigidez arterial, foram a duração do Diabetes, a Pressão arterial diastólica e o HDL. Apesar da correlação entre o uso de drogas com propriedades hemorreológicas e a rigidez arterial, a exclusão dos pacientes usuários daqueles medicamentos não alterou os resultados obtidos. Concluímos que, na população de diabéticos tipo 1 estudada, a resposta vascular endotélio dependente, e a capacidade máxima de vasodilatação estão significativamente reduzidas. Não houve diferença entre diabéticos e controles quanto à rigidez arterial. Ademais, a vasodilatação microcirculatória mediada pela Acetilcolina pode ser correlacionada com a rigidez arterial em diabéticos. Estudos posteriores devem ser realizados no intuito de avaliar a influência exercida pelas drogas que alteram a função endotelial sobre a reatividade micro e macrovascular.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:54:32Z No. of bitstreams: 1 Tese final1.pdf: 1240852 bytes, checksum: e4bcb6efa28717cc0968db2dde911d08 (MD5) Made available in DSpace on 2021-01-06T20:54:32Z (GMT). No. of bitstreams: 1 Tese final1.pdf: 1240852 bytes, checksum: e4bcb6efa28717cc0968db2dde911d08 (MD5) Previous issue date: 2010-02-03 Recent clinical evidence suggests that calcium-rich diets help reduce body weight and abdominal obesity; increase insulin sensitivity; enhance lipid profile; modulate blood pressure and reduces the inflammatory state associated with obesity. The Objective: evaluate the effects of dietary calcium during energy restriction on weight loss, body fat, abdominal obesity, glucose metabolism, lipid profile, leptin levels, blood pressure, biomarkers of inflammation, fibrinolysis, biomarkers of endothelial function and calcium metabolism in obese subjects. The study was a randomized clinical trial. The participants were randomized into a low calcium diet (LCD) (

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:57:41Z No. of bitstreams: 1 Livia de Paula Nogueira Dissertacao completa.pdf: 942451 bytes, checksum: 49bbfe1402b4766de083ba8d06602190 (MD5) Made available in DSpace on 2021-01-06T20:57:41Z (GMT). No. of bitstreams: 1 Livia de Paula Nogueira Dissertacao completa.pdf: 942451 bytes, checksum: 49bbfe1402b4766de083ba8d06602190 (MD5) Previous issue date: 2009-12-29 Conselho Nacional de Desenvolvimento Científico e Tecnológico It is estimated that approximately 30 millions of Brazilians are suffering from hypertension and despite the extreme number of hypotensive available it is believed that only 2.7 million are being treated properly. Recently several clinical, epidemiological and experimental studies have shown an association between the consumption of foods rich in cocoa and lowering blood pressure as well as relating this effect to a possible action of the cocoa flavonoids on endothelial function. Objective: to evaluate in hypertensive patients, stage 1, the effect of administration of the flavonoids of dark chocolate 70% cocoa on the arterial pressure, endothelial function, and the relationship between variations on blood pressure and endothelial function. Type of the study: experimental, clinical and open. Casuistic: 20 patients, without distinction of race or sex, with primary hypertension stage 1, without antihypertensive treatment prior normal weight, overweight or obese grade I, aged between 18 and 60. Site of the study: Clinical and Experimental Pathophysiological Laboratory Clinex. Rio de Janeiro State University. Variables studied: blood pressure, HS-CRP, IL-6, TNF-α, VCAM, ICAM, E-selectin, OX-LDL, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, blood glucose, insulin, HOMA, body mass index, waist circumference, hip circumference, waist hip ratio and body fat. Results: the chocolate-cocoa 70% significantly reduced the blood pressure measured by casual oscillometric method. Through this method we observed that systolic blood pressure decreased significantly after 4 weeks of treatment, (V0: 146.50 ± 1.28, V1: 140.40 ± 3.02, V2: 138.50 ± 2.44; V3: 140.60 ± 2.50; V4: 136.90 ± 2.60, V4 vs. VO, p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:40:02Z No. of bitstreams: 1 Dissertacao-Tarik de Almeida Isbele.pdf: 690192 bytes, checksum: b4fd74b94171baaa03cde01cbac01d5d (MD5) Made available in DSpace on 2021-01-05T19:40:02Z (GMT). No. of bitstreams: 1 Dissertacao-Tarik de Almeida Isbele.pdf: 690192 bytes, checksum: b4fd74b94171baaa03cde01cbac01d5d (MD5) Previous issue date: 2009-12-09 Fundação de Amparo a Pesquisa do Estado de Minas Gerais Observational studies have demonstrated that weight gain and increase of abdominal circumference are important prognostic indexes in hypertension, and abdominal obesity is a relevant marker of increased cardiovascular risk. The purpose of this study was to identify metabolic and cardiac alterations in a sample of non-diabetic hypertensive women with abdominal obesity. In a cross-sectional study, 120 hypertensive women aged 40-65 years were included and separated in groups without abdominal obesity (AO-, n=42) and with abdominal obesity (AO+, n=78) according waist circumference < or ≥ 88cm, respectively. The participants of this study were submitted to clinical and anthropometric evaluation, and blood and urine were collected for biochemical tests. Afterwards, electrocardiography, echocardiography, and carotid ultrasound were performed. The mean age was 53 years in both groups. The diastolic blood pressure was significantly higher in the group AO+ (90±1 vs 85±1 mmHg, p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:59:02Z No. of bitstreams: 1 Dissertacao Marcela Paranhos Knibel.pdf: 879409 bytes, checksum: 670472a727d06d452873e7cdc8752513 (MD5) Made available in DSpace on 2021-01-06T20:59:02Z (GMT). No. of bitstreams: 1 Dissertacao Marcela Paranhos Knibel.pdf: 879409 bytes, checksum: 670472a727d06d452873e7cdc8752513 (MD5) Previous issue date: 2009-11-25 Conselho Nacional de Desenvolvimento Científico e Tecnológico It is estimated that approximately 30 million Brazilians are suffering from hypertension and despite the large amount of hypotensive available, it is believed that only 2.7 million are being treated properly. Recently several clinical studies, epidemiological and experimental studies have shown an association between the consumption of foods rich in cocoa and lowering blood pressure as well as relating this effect to a possible action of the cocoa flavonoids on endothelial function. To evaluate in hypertensive patients, stage I, the effect of administration of the cocoa flavonoids present in chocolate, 70% of: blood pressure, endothelial function, the speed of the pulse wave, and the relationship between variations in blood pressure and endothelial function. The type of the study was experimental, clinical and open. Twenty patients, without distinction of race or sex, with essential hypertension stage I, without antihypertensive treatment prior normal weight, overweight or obese grade I, aged between 18 and 60. Local of study, Department of Clinical and Experimental Pathophysiology - were enrolled. State University of Rio de Janeiro. We studied blood pressure (oscillometric method and by ambulatory blood pressure), index of reactive hyperemia (by peripheral arterial tonometry by Endo-PAT 2000), augmentation index (by peripheral arterial tonometry by Endo-PAT 2000), speed pulse wave (through COMPLIOR SP), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, blood glucose, body mass index, waist circumference, hip circumference, waist-hip ratio and body fat. The chocolate-cocoa 70% significantly reduced the blood pressure measured by oscillometric method. Through this method we observed that systolic blood pressure decreased significantly after 4 weeks of treatment, (V0: 146.50 ± 1.28, V1: 140.40 ± 3.02, V2: 138.50 ± 2.44; V3: 140.60 ± 2.50; V4: 136.90 ± 2.60; vs V4. V0, p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:58:43Z No. of bitstreams: 1 Cyro Jose de Moraes Martins Completa.pdf: 2611858 bytes, checksum: fbf2dbb170fada9b76878b0ec350a8cb (MD5) Made available in DSpace on 2021-01-06T20:58:43Z (GMT). No. of bitstreams: 1 Cyro Jose de Moraes Martins Completa.pdf: 2611858 bytes, checksum: fbf2dbb170fada9b76878b0ec350a8cb (MD5) Previous issue date: 2009-09-30 The aim of this study was the assessment of the cross-sectional associations of the adipokines (leptin system and adiponectin) with cardiometabolic risk factors, insulin resistance and the metabolic syndrome phenotype in a multiethnic population with varying degrees of adiposity. The leptin system consists of plasma leptin, soluble leptin receptor and the free leptin index, calculated as the ratio of the concentrations of leptin and soluble leptin receptor. One hundred and seventy three subjects (aged 45±12 years; 124 women; body mass index 35.6±9.5 kg/m2) were selected among 310 individuals referred to participate in a study on genetic markers of cardiometabolic risk factors. Blood samples were assessed for metabolic profile, adiponectin, leptin and its soluble receptor levels. Leptin and soluble leptin receptor were inversely correlated, but adiponectin was not significantly correlated with the other adipokines. Leptin and free leptin index were positively associated with cardiometabolic risk factors, except for total cholesterol; contrariwise, both variables were inversely related to HDL-cholesterol. Soluble leptin receptor exhibited an inverse relation to cardiometabolic risk factors, except for plasma glucose and lipid parameters (P ≤ 0.006 for all cases). Adiponectin was inversely related to waist-to-hip ratio, homeostasis model assessment index, and insulin (P ≤ 0.005 for all cases). Leptin and free leptin index increased, whereas soluble leptin receptor decreased across tertiles of body mass index, waist circumference, waist-to-hip ratio, systolic blood pressure, homeostasis model assessment index and with increasing number of metabolic syndrome components (P for trend < 0.05 for all cases). In multivariable models, sex, body mass index and insulin were independently associated with leptin and free leptin index, whereas age, sex, body mass index and systolic blood pressure were the independent correlates of soluble leptin receptor. Relating all adipokines conjointly to metabolic syndrome, only leptin demonstrated independent association with the phenotype (odds ratio, 3.35; 95% confidence interval, 1.90 - 5.91; P < 0.001). In this multiethnic population, the leptin system and adiponectin were associated with cardiometabolic risk factors, insulin resistance and the metabolic syndrome phenotype. O objetivo desse estudo foi avaliar a associação das adipocitocinas (sistema leptina e adiponectina) com fatores de risco cardiometabólico, grau de resistência insulínica e fenótipo de síndrome metabólica em uma população de origem multiétnica com variados graus de adiposidade. O sistema leptina é constituído pela leptina plasmática, receptor solúvel de leptina e índice de leptina livre, este último calculado como a razão entre a leptina e seu receptor solúvel. Cento e setenta e três indivíduos (idade, 45 ± 12 anos; 124 mulheres; índice de massa corporal, 35,6 ± 9,5 kg/m2) foram selecionados entre 310 participantes de um estudo sobre marcadores genéticos de fatores de risco cardiometabólico, e avaliados do ponto de vista antropométrico, hemodinâmico e laboratorial, para determinar o seu perfil metabólico e as concentrações de adiponectina, leptina e receptor solúvel de leptina. Os níveis de leptina mostraram correlação inversa com as concentrações de seu receptor solúvel, porém a adiponectina não mostrou associação significativa com o sistema leptina. A leptina e o índice de leptina livre se associaram positivamente com os fatores de risco cardiometabólico (P ≤ 0,006), exceto colesterol total, e negativamente com o HDL-colesterol (P ≤ 0,005), ao contrário do receptor solúvel da leptina, que exibiu relação inversa com os fatores de risco (P < 0,001), exceto glicose e parâmetros lipídicos. A adiponectina associou-se inversamente com a relação cintura/quadril, HOMA-IR e concentração plasmática de insulina (P ≤ 0,005). Os valores de leptina e índice de leptina livre aumentaram, e de receptor solúvel diminuíram ao longo dos tercis de índice de massa corporal, circunferência da cintura, relação cintura/quadril, pressão arterial sistólica, HOMA-IR e também com o aumento no número de componentes da síndrome metabólica (P para tendência

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:58:37Z No. of bitstreams: 1 Alessandro Rodrigues do Nascimento Final.pdf: 855907 bytes, checksum: 090cf11a9286a3b7fda734d0aa96817c (MD5) Made available in DSpace on 2021-01-06T20:58:37Z (GMT). No. of bitstreams: 1 Alessandro Rodrigues do Nascimento Final.pdf: 855907 bytes, checksum: 090cf11a9286a3b7fda734d0aa96817c (MD5) Previous issue date: 2009-08-24 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Essential hypertension (EH) is characterized by chronic increases in peripheral vascular resistance, mainly resulting from functional and structural alterations of the microcirculation. Moreover, a reduction of arteriolar and capillary density (microvascular rarefaction) is involved in the increase of arterial pressure in EH. In addition, central sympathetic overactivity is involved in the pathophysiology of functional and structural alterations of the cardiovascular system in EH. In the present work, we investigated the effects of a long-term treatment (28 days) with centrally-acting antihypertensive drugs on functional and/or structural capillary rarefaction in the skin, skeletal muscle and heart of adult spontaneously hypertensive rats (SHR), a classical experimental model of EH. We also investigated the effects of the treatments on left ventricular mass in SHR. Wistar Kyoto rats were used as normotensive controls. We used equipotent anihypertensive doses of clonidine (0.1 mg/kg/day), rilmenidine (1 mg/kg/day) and moxonidine (10 mg/kg/day). Functional capillary density was evaluated using epi-illuminated fluorescence video-microscopy while structural capillary density was studied using a histochemical tracer of capillaries. Our results showed that there was an increase in the number of spontaneously perfused capillaries (functional density) in the skin and skeletal muscle of SHR in all treatment groups, when compared to the non-treated SHR group. Moreover, there was a reversion of structural capillary rarefaction in the skeletal muscle with all drug treatments. On the other hand, there was no reversion of structural capillary rarefaction of the left ventricle in any experimental group. Finally, left ventricular hypertrophy was partially reversed in the group of SHR treated with rilmenidine. In conclusion, our results showed that besides arterial pressure reduction, long-term treatment with centrally-acting antihypertensive drugs induces a reversal of microcirculatory alterations in SHR and rilmenidine favors the regression of left ventricular hypertrophy. The results also suggest that the modulation of central sympathetic overactivity induces beneficial effects on the microcirculation in the hypertensive disease. A hipertensão arterial sistêmica (HAS) caracteriza-se pelo aumento crônico da resistência vascular periférica, determinado essencialmente na microcirculação, que resulta de alterações vasculares funcionais e estruturais. Além disso, a redução da densidade arteriolar e capilar (rarefação da microcirculação) contribui para a elevação da pressão arterial na HAS. Nesse contexto, sabe-se que a hiperatividade do sistema nervoso simpático central está envolvida na fisiopatologia das alterações tanto funcionais quanto estruturais da HAS. No presente trabalho, investigamos os efeitos do tratamento crônico (28 dias) com anti-hipertensivos de ação central sobre a rarefação capilar funcional e/ou estrutural na pele, músculo esquelético e miocárdio de ratos espontaneamente hipertensos (SHR) adultos, modelo clássico de hipertensão arterial primária. Os ratos Wistar Kyoto (WKY) foram utilizados como controles normotensos. Foram utilizadas doses equipotentes de clonidina (0,1 mg/kg/dia), rilmenidina (1 mg/kg/dia) e moxonidina (10 mg/kg/dia), com relação ao efeito anti-hipertensivo. Também foram estudados os efeitos dos tratamentos sobre a massa ventricular esquerda. Para avaliação da densidade capilar funcional utilizamos microscopia por epi-iluminação e fluorescência e para avaliação da densidade capilar estrutural técnicas de marcação histoquímica dos capilares. Os resultados mostraram que houve aumento do número de capilares espontaneamente perfundidos (densidade funcional) na pele e no músculo esquelético de SHR tratados com todos os fármacos, com relação ao grupo SHR não tratado. Além disso, foi observada reversão da rarefação capilar estrutural no músculo esquelético de SHR com todas as drogas utilizadas. Por outro lado, não houve reversão da rarefação capilar estrutural no ventrículo esquerdo em nenhum grupo experimental. Finalmente, a hipertrofia do ventrículo esquerdo foi parcialmente revertida em SHR tratados com rilmenidina. Em conclusão, nossos resultados demonstraram que, além da redução da pressão arterial, a utilização de agentes anti-hipertensivos de ação central resulta na reversão de alterações microcirculatórias de ratos espontaneamente hipertensos e o uso de rilmenidina favorece a regressão da hipertrofia cardíaca. Os resultados também sugerem que a inibição da hiperatividade simpática central induz efeitos benéficos na microcirculação na hipertensão arterial.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:58:49Z No. of bitstreams: 1 Valter Gabriel Maluly Completa.pdf: 713901 bytes, checksum: 0f362613ef0379e732174b5980a516a1 (MD5) Made available in DSpace on 2021-01-06T20:58:49Z (GMT). No. of bitstreams: 1 Valter Gabriel Maluly Completa.pdf: 713901 bytes, checksum: 0f362613ef0379e732174b5980a516a1 (MD5) Previous issue date: 2009-04-29 Context: there are many scientific evidences that magnesium plays a very important role in the physiologic regulation of the blood pressure and glucose metabolism. The alterations of the intracellular homeostasis of this cation, could participate in a very important way in the physiopathologic mechanisms that contribute to the development of arterial hypertension and insulin resistance. Magnesium can influence the blood pressure by modulating the tonus and vascular structure and many effects in biochemical reactions that can control the vascular contractility, the inflammation and the insulin sensibility. Many trials aim that a long term use of diuretic in the treatment of hypertension can induce a depletion of intracellular magnesium. Objectives: to evaluate the effect of oral supplementation of magnesium in hypertension, the intra-erythrocyte concentration of magnesium and sodium and the insulin resistance in primary hypertensive patients treated with thiazidic diuretic. Study design: a randomized, double blind clinical trial was performed. Thirty nine primary hypertensive patients in first stage were distributed in two groups. One group received 20 patients and the other 19. After a period of wash out of two weeks one group received thiazidic diuretic (25mg) and magnesium (240mg of element magnesium) and the other group received thiazidic diuretic (25mg) and placebo during 16 weeks. The patients were evaluated once a month. In the visit 1 (after wash out) and visit 5 (final of the study), they were evaluated in their blood pressure by AMBP (ambulatory monitoring of blood pressure), the intracellular concentration of magnesium and sodium and of the insulin sensibility. In the visit 2 and visit 4, the patients were clinically evaluated and the blood pressure was measured by auscultatory method. Methods: the blood pressure evaluation was made by auscultatory method and AMBP (ambulatory monitoring of blood pressure by space labs). The intra-erythrocyte concentration of magnesium was made by atomic absorption and the concentration of sodium by flame photometer. The plasmatic insulin was measured by radioimmunoassay and the index of insulin resistance by the formulae of homeostatic model evaluation (HOMA). Results: after 16 weeks using diuretic plus magnesium or diuretic plus placebo we observed significative reduction of the blood pressure evaluated by auscultatory method and by ambulatory monitoring blood pressure (AMBP) during 24 hour in the two groups; although there was no significative difference between the reductions of the blood pressure when we compare the two groups. In the group with diuretic plus placebo the reduction of the blood pressure was of 22,30 ±2,44mmhg (p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:43:38Z No. of bitstreams: 1 Erika Maria Goncalves Campana Dissertacao completa.pdf: 1500498 bytes, checksum: 93feeb78f97e8bc289b6214beb09944c (MD5) Made available in DSpace on 2021-01-05T19:43:38Z (GMT). No. of bitstreams: 1 Erika Maria Goncalves Campana Dissertacao completa.pdf: 1500498 bytes, checksum: 93feeb78f97e8bc289b6214beb09944c (MD5) Previous issue date: 2008-12-03 Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro Cardiovascular risk variables studies in young populations are important for primary prevention strategies. The objectives of the present study are the following: To evaluate BP, anthropometric and metabolic variables obtained during a 17 year-old period of follow-up in young subjects from the Rio de Janeiro Study. 115 subjects (64M) were submitted to three evaluations along 17 years (212,23±16,0months): E1 (12,97±1,48yo), E2(21,90±1,71yo) and E3 (30,65±2,00yo), and were divided in two groups: GN (n=84) normal BP in at least two evaluations; GH (n=31) abnormal BP in at least two evaluations. In the three occasions, BP and body mass index (BMI) were obtained. In E2 and E3, glucose, total cholesterol, LDL-c and HDL-c, triglycerides were added and in E3, abdominal circumference (AC) was also measured. The main results were: 1) Group H had higher BP, BMI and AC (p

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T18:13:54Z No. of bitstreams: 1 Leonardo de Souza Mendonca Dissertacao completa.pdf: 2505143 bytes, checksum: 4d9a1673d6f2e999e11c7391b1266bf1 (MD5) Made available in DSpace on 2021-01-05T18:13:54Z (GMT). No. of bitstreams: 1 Leonardo de Souza Mendonca Dissertacao completa.pdf: 2505143 bytes, checksum: 4d9a1673d6f2e999e11c7391b1266bf1 (MD5) Previous issue date: 2007-02-16 Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro Menopause and hypertension independently may alter cardiovascular remodeling, but little is known about their association on left ventricular and aortic wall remodeling. Rats were separated into four groups of six animals each: Sham group, OVX group (ovariectomized rats), 2K1C (two kidneys one clip rats), and OVX+2K1C group, and leaved for 11 weeks. Left ventricle (LV) and thoracic aorta were removed and analyzed (light microscopy, immunohistochemistry and stereology). Vaginal cytology showed Sham and 2K1C rats cycling normally, whereas OVX and OVX+2K1C rats were persistently in diestrus or proestrus. Blood pressure compared to the Sham group increased 12% in the OVX group, 35% higher in both the 2K1C and OVX+2K1C groups. The LV mass/tibia length ratio and the cross-sectional area of cardiomyocytes increased in all groups except the Sham group. The intramyocardial vascularization was reduced around 30% in relation to the Sham group, with no difference among OVX, 2K1C and OVX+2K1C groups. The cardiac interstitium increased more than 45% in groups 2K1C and OVX+2K1C comparing to the Sham group, but no significant difference was seen between the Sham and the OVX groups. The number of LV cardiomyocyte nuclei was gradually smaller in the OVX group followed by the 2K1C group and the OVX+2K1C group, with no difference between the 2K1C and the OVX+2K1C groups. Positive immunostaining for angiotensin II AT1 receptor was observed in smooth muscle cell layer of the aortic tunica media in all groups. Present findings demonstrated that ovariectomy and renovascular hypertension act independently enhancing BP in rats, the stimulus to elevated BP being stronger, as well as the consequences to the adverse cardiac remodeling, in renovascular hypertension than in surgically-induced menopause. A menopausa e a hipertensão podem alterar o remodelamento cardiovascular, porém pouco se sabe sobre sua associação no remodelamento ventricular esquerdo e na aorta. As ratas foram separadas em quatro grupos com seis animais cada: grupo Sham, OVX (ratas ooforectomizadas), 2K1C (ratas com dois rins, um clipe), e grupo 2K1C+OVX com período experimental de 11 semanas. O ventrículo esquerdo (VE) e a aorta torácica foram removidos e analisados (microscopia de luz, imuno-histoquímica e estereologia). A citologia vaginal mostrou que os animais dos grupos Sham e 2K1C ciclaram normalmente, entretanto, os animais dos grupos OVX e OVK+2K1C permaneceram na fase do diestro ou proestro. Comparado ao grupo Sham, a pressão arterial aumentou 12% no grupo OVX e 35% maior nos grupos 2K1C e OVX+2K1C. A relação massa do VE/comprimento da tíbia e a área seccional média de cardiomiócitos aumentaram em todos os grupos com exceção do grupo Sham. A vascularização intramiocárdica foi reduzida cerca de 30% em relação ao grupo Sham, não havendo diferença significativa entre os grupos OVX, 2K1C e OVX+2K1C. O tecido conjuntivo cardíaco teve um aumento superior a 45% nos grupos 2K1C e OVX+2K1C comparados ao grupo Sham, sem diferença entre o os animais do grupo Sham e OVX. O número de núcleos de cardiomiócitos do VE foi gradualmente menor nos grupos OVX, 2K1C e OVX+2K1C, sem diferença entre os dois últimos grupos. Imuno-histoquímica positiva para receptor AT1 da Ang II nas células musculares lisas da túnica média da aorta foi observado em todos os grupos. Estes resultados indicam que a ooforectomia e a hipertensão renovascular agem aumentando a pressão arterial independentemente, com conseqüente remodelamento cardíaco adverso, com estímulo maior da hipertensão renovascular que da menopausa induzida cirurgicamente.