abstract: The Western Pattern diet has been characterized by having greater than 50 percent consumption coming from fat and sugar. This macronutrient allocation has been shown to have deleterious effects on endothelial function and metabolic markers of cardiovascular disease. Exercise has been shown to improve vascular reactivity and metabolic markers related to cardiovascular health. The objective of the study was to determine if exercise training can prevent the anticipated deleterious effects of a fat-sugar supplemented diet on endothelial function and blood markers of cardiovascular risk in young men. Twenty-one, healthy college-aged males were randomly assigned to either the doughnut + exercise or doughnut only groups. Both groups were fed 2 doughnuts per day, 6 days per week, for three weeks, while maintain their current diet. The exercise group completed 4 exercise training sessions per week consisting of 2 high intensity interval training bouts (up to 95% VO2peak) on a cycle ergometer and two moderate intensity, steady-state bouts (at 75% VO2peak) on a treadmill. Changes in body weight and composition, markers of endothelial function, oxidative stress, serum lipids, and blood glucose were measured in each group. As expected, cardiovascular fitness increased significantly in the doughnut-supplemented + exercise group as compared to the doughnut-supplemented (p=0.005). Significant increases in body weight (p=0.036), fat mass (p=0.013), and body fat percentage (p=0.014) were seen in the doughnut only group as compared to the doughnut + exercise group. The doughnut + exercise group showed significant improvements in fasting serum triglycerides (p=0.036), plasma insulin (p=0.039) and insulin sensitivity (HOMA; p=0.05) as compared to the doughnut only group. The doughnut + exercise group saw a significant improvement in nitric oxide availability whereas the doughnut only group experienced a significant decline (p=0.014). There were no significant changes in other markers. Despite the addition of a fat/sugar supplement of ~11,600 kcal over three weeks, 4 exercise sessions per week were sufficient to prevent a gain in body weight and fat mass, and also improve some measures of cardiometabolic risk. These results suggest that exercise may be necessary to prevent some adverse health outcomes associated with transient periods of excessive energy consumption. / Dissertation/Thesis / Ph.D. Physical Activity, Nutrition and Wellness 2013

Introdução: Ensaios clínicos demonstram que pacientes com doença arterial coronariana, submetidos a programa de reabilitação cardíaca, apresentam melhora na função endotelial dependente do endotélio, porém a intensidade do exercício com maior benefício não é conhecida. Objetivo: Comparar os efeitos de duas intensidades de exercício aeróbio sobre a resposta vasodilatadora braquial dependente e independente do endotélio em pacientes com doença arterial coronariana. Métodos: 33 pacientes pós-infarto agudo do miocárdio, do sexo masculino, com idade média (58±6), foram randomizados para: treinamento em cicloergômetro de alta intensidade (AI) (80-85% da freqüência cardíaca máxima; n = 16); ou de moderada intensidade (MI) (65-70 % da freqüência cardíaca máxima; n = 17). O treinamento foi realizado por 45 minutos, 5 vezes por semana. Antes e após 4 semanas de treinamento, os pacientes realizaram teste de esforço com Protocolo de Ellestad e estudo da função endotelial braquial, por ultra-som de alta resolução da artéria braquial. Resultados: O treinamento em AI resultou em maior aumento da capacidade funcional avaliada pelo tempo de máximo tolerado no teste de esforço (AI de 7,45 ± 1,52 para 9,01 ± 1,94 min e MI de 7,55 ± 1,79 para 7,63±1,68 min). O grupo AI também apresentou maior aumento do fluxo da artéria braquial após hiperemia reativa (dependente do endotélio) e após uso de nitrato sublingual (independente do endotélio). Conclusão: Quando comparado ao treinamento de moderada intensidade, o treinamento aeróbio de alta intensidade resulta em maior aumento da capacidade funcional e da resposta vasodilatadora dependente e independente do endotélio em pacientes com doença arterial coronariana. / Introduction: Clinical essays show that patients with coronary artery disease when submitted under a cardiac rehabilitation program present improvement of endothelium dependent endothelial function, however benefits of the exercise intensity are still unknown. Aim: To compare the intensities of aerobic exercise over dependent and independent brachial vasodilation response in patients with coronary artery disease Methods: 33 post acute myocardium infarct males patients, with a mean age of 58 + 6, were randomized trained in high-intensity cycle-ergonomics (AI), (80-85% from maximal cardiac frequency n = 16); or moderate intensity (MI) (65-70 % from maximal cardiac frequency n = 17). Trainings lasted for 45 minutes, 5 times a week. Before and after 4 weeks of training patients underwent maximal treadmill stress tests with Ellestad Protocol and studies of brachial-endothelial function. Results: Training in AI group resulted in increased functional fitness, when assesses by endurance time at treadmill exercise test (AI from 7,45 ± 1,52 to 9,01 ± 1,94 min and MI from 7,55 ± 1,79 to 7,63±1,68 min). Also, AI group presented greater augment of brachial artery flow after reactive hyperemia (endothelium-dependent) and after the sublingual intake of nitrate (endothelium-independent). Conclusion: High-intensity aerobic training compared to moderate-intensity training results in greater functional capacity and endothelium dependent and independent vasodilation response in patients with coronary arterial disease.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-05-18T15:15:11Z No. of bitstreams: 1 patriciadecastrodaibert.pdf: 2626516 bytes, checksum: 4aa00de0747d969c75ff06dd33f4502a (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-01T18:50:12Z (GMT) No. of bitstreams: 1 patriciadecastrodaibert.pdf: 2626516 bytes, checksum: 4aa00de0747d969c75ff06dd33f4502a (MD5) / Made available in DSpace on 2016-07-01T18:50:12Z (GMT). No. of bitstreams: 1 patriciadecastrodaibert.pdf: 2626516 bytes, checksum: 4aa00de0747d969c75ff06dd33f4502a (MD5) Previous issue date: 2012-03-29 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A doença renal crônica é considerada um problema de saúde pública mundial, principalmente devido à alta morbidade e mortalidade. A perda progressiva e irreversível da função renal fornece várias complicações. Avaliação dos fatores de risco é fundamental para reduzir riscos de morte em doentes renais crônicos. Doença cardiovascular representa a principal causa de morte dessa doença seguida por infecções. Com o objetivo de avaliar a função endotelial foram incluídos 35 pacientes alocados em três grupos (15 com doença renal crônica e periodontite crônica, 10 com periodontite crônica sem doenças sistêmicas e 10 controles saudáveis). Doença renal crônica foi definida como sugerido pelo Guia de Prática Clínica da National Kidney Foundation. Periodontite Crônica foi definida através de profundidade de sondagem e nível de inserção clínica, segundo a Academia Americana de Periodontologia. Níveis de proteína C-reativa foram mensurados pela técnica Elisa. A função endotelial apresentou-se reduzida em pacientes com doença renal crônica e periodontite crônica e naqueles com periodontite crônica sem doenças sistêmicas quando comparados ao grupo controle saudável. Níveis de proteína C-reativa apresentaram-se elevados nos grupos com doença renal crônica com periodontite crônica e periodontite crônica sem doenças sistêmicas em relação ao grupo controle. Pacientes com nível de inserção clínica ≥ 6 mm foram mais encontrados no grupo de doentes renais crônicos com periodontite crônica com diferença estatisticamente significante quando comparado aos outros dois grupos. Conclui-se que a periodontite crônica induz uma resposta inflamatória sistêmica e pacientes portadores de doença renal crônica apresentam-a com maior gravidade. / Chronic kidney disease is considered a public health problem worldwide, mainly due to the high morbidity and mortality. The progressive and irreversible loss of renal function provides several complications. Evaluation of risk factors is key to reducing risks of death in patients with chronic renal failure. Cardiovascular disease is the leading cause of death by disease after infection. In order to assess endothelial function were included 35 patients divided into three groups (15 with chronic kidney disease and chronic periodontitis, 10 with chronic periodontitis with no systemic disease and 10 healthy controls). Chronic kidney disease was defined as suggested by the Practice Guideline for the National Kidney Foundation. Chronic periodontitis was defined by probing depth and clinical attachment level, according to the American Academy of Periodontology. Levels of C-reactive protein were measured by ELISA technique. Endothelial function was presented reduced in patients with chronic kidney disease and those with chronic periodontitis and chronic periodontitis with no systemic disease compared to healthy control group. Levels of C-reactive protein had to be high in groups with chronic kidney disease with chronic periodontitis and chronic periodontitis with no systemic diseases in the control group. Patients with clinical attachment level ≥ 6 mm were more in the group with chronic renal failure patients with chronic periodontitis was statistically significant when compared to the other two groups. Chronic periodontitis induces a systemic inflammatory response and patients with chronic kidney disease presented with the utmost gravity.

No description available.

There is growing evidence to suggest that vascular disease plays an important role in late life depressive disorder. The aim of this study was to characterize vascular impairment in late life depression. Assessment of endothelial function, arterial stiffness, and atherosclerosis in a variety of vessel beds was carried out in 25 subjects with late life depression and 21 nondepressed control subjects. All study subjects underwent wave velocity, pulse wave analysis, carotid intima media thickness analysis, and magnetic resonance imaging of the brain and a subset gluteal fat biopsy and direct assessment of small artery endothelial function. There were no baseline differences in demographics or a range of vascular risk factors between the groups. There was a generalised vascular dysfunction in depressed subjects with significantly more atherosclerosis, poorer endothelial function and increased arterial stiffness. On neuroimaging, depressed subjects had significantly more dilated Virchow-Robin spaces in the basal ganglia. White matter lesion volumes in all regions were higher in depressed subjects but not significantly so. Furthermore, subjects with late onset depression (onset >60years) had greater vascular impairment when compared to those with early onset illness. Lastly, depressed subjects who did not respond to antidepressant monotherapy showed more vascular dysfunction compared to responders. The study has a number of limitations including the small sample size and as the study was cross sectional, the observed relationship between vascular dysfunction and depression is associative rather than causal. Further research in larger samples is required to address the methodological limitations of this study. If the study results are confirmed, the use of vasoprotective drugs to improve vascular function or retard atherosclerosis as diasease modifying agents in late life depression would be a rational development.

Introduction: SLE is associated with pro-atherogenic metabolic derangement and an elevated cardiovascular risk. The vascular endothelium may be a key interface between active SLE and premature atherosclerosis. Improved understanding of the contribution of inflammation and its management to cardiovascular risk in SLE will inform personalised treatment decisions in SLE patients. Methods: Data from an international inception cohort was used to investigate the relationship between inflammatory disease activity, lupus phenotype and corticosteroid exposure and the metabolic syndrome (MetS) over 2 years in SLE patients. The relationship between disease activity (BILAG-2004) and markers of endothelial function (flow-mediated dilatation (FMD) of the brachial artery) and endothelial damage (endothelial microparticles (EMPs)) following a change in anti-inflammatory therapy was investigated in a longitudinal cohort of patients with active SLE. Results: MetS was common in young SLE patients (12.6-16.0%) over the initial 2 years of disease. Factors independently associated with developing MetS over the 2-year study period were (odds ratio (95% CI)) Hispanic ethnicity (3.47 (1.76, 6.86)), higher initial peak corticosteroid dose (1.02 (1.01,1.03)), and elevated anti-dsDNA antibodies at study entry (1.86(1.19,2.81)). MetS was often persistent and preceding MetS strongly predicted future MetS (4.83 (2.93, 7.87)). Patients with active SLE had reduced FMD (median (IQR) FMD 1.63% (-1.22, 5.32) vs. 5.40% (3.02, 8.57); p = 0.05) and elevated EMPs (157,548/ml (59,906, 272,643) vs. 41,025 (30,179, 98,082); p = 0.003) compared to age-matched controls. Both improved following a change in anti-inflammatory therapy, and correlated moderately with change in disease activity over time. Conclusions: Inflammatory disease activity and higher doses of corticosteroids in very early disease influence the development of MetS in SLE, which can become persistent. Endothelial dysfunction is common in patients with active SLE but can be improved with better disease control. Therefore even from disease onset, therapeutic regimes should be individually tailored to achieve good disease control whilst minimising corticosteroid doses, to improve cardiovascular risk surrogates in SLE.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19400号 / 医博第4051号 / 新制||医||1012(附属図書館) / 32425 / 京都大学大学院医学研究科医学専攻 / (主査)教授 横出 正之, 教授 福原 俊一, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Cerebral palsy (CP) is a disability that impacts a person throughout their lifespan and may place adults with the condition at an increased risk of physical inactivity and cardiovascular disease. Cardiovascular structure and function in adults with CP has not been comprehensively investigated previously. In the current cross-sectional, observational study, endothelial function, carotid distensibility, and arterial stiffness were assessed using flow-mediated dilation (FMD), B-mode ultrasound, and pulse wave velocity (PWV), respectively, in forty adults with CP (age 33.7 ± 12.7 years). The study sample was separated based on whether subjects were community ambulant or community non-ambulant using the Gross Motor Function Classification System (GMFCS). Those in GMFCS I-II were labeled community ambulant (age 31.7 ± 10.4 years) while those in GMFCS III-V were community non-ambulant (age 34.8 ± 13.6 years). Resting arterial stiffness was examined through assessment of central and upper and lower limb peripheral PWV (cPWV, uPWV, lPWV). Carotid intima-media thickness (IMT), a measure of vascular structure, was also quantified using B-mode ultrasound images and a semi-automated edge detection software program. cPWV was calculated using the distance (carotid to femoral using the subtraction method) and time delay between the foot of the carotid waveform and the foot of the femoral waveform. uPWV was calculated from the carotid to radial artery distance (subtracting the distance from the carotid to sternal notch from the carotid to radial distance) and the time delay between the arrival of the foot of each corresponding waveform. lPWV was calculated from the femoral to posterior tibialis artery using the distance between each site and time delay between the arrival of the foot of each corresponding waveform. Physical activity (PA) levels were assessed using Actigraph accelerometry with cut points that had been previously determined in normal adults. Cardiometabolic markers of fasting serum interleukin-6, insulin, glucose, and a lipid panel were analyzed. The non-ambulant group had an increased uPWV (10.2 m/s ± 1.9) compared to the ambulant group (8.28 m/s ± 1.6) (p<0.01) despite no differences in cPWV or lPWV. There were no group differences (p>0.05) in absolute, relative or normalized FMD responses. Both groups also had similar values of carotid IMT and carotid distensibility. No group differences were found in any of the cardiometabolic or inflammatory markers. Moderate-to-vigorous PA (MVPA) levels were greater in the ambulant group (2.4 mins ± 2.1 per hour) compared to the non-ambulant group (0.3 mins ± 0.6 per hour) (p<0.01). Furthermore, sedentary time was greater in the non-ambulant group (57.8 mins ± 1.9 per hour) compared to the ambulant group (51.6 mins ± 4.7 per hour) (p<0.01). Despite differences in PA levels, MVPA was not a significant independent predictor of vascular or metabolic health in this cohort of adults with CP. However, GMFCS level was predictive of both uPWV and resting heart rate. Future research should include adults with CP who are older in age to gain further insight into the potential consequences of an activity-limited lifestyle (specifically in the non-ambulant group) on cardiovascular and metabolic health in this clinical population. / Thesis / Master of Science in Kinesiology

No description available.

Aims: Oxidative stress and inflammation contribute to atherogenesis. Rac1 GTPase regulates pro-oxidant NADPH oxidase activity, reactive oxygen species (ROS) formation, actin cytoskeleton organization and monocyte adhesion. We investigated the vascular effects of pharmacological inhibition of Rac1 GTPase in mice. Methods and Results: We treated wild-type and apolipoprotein E-deficient (ApoE−/−) mice with Clostridium sordellii lethal toxin (LT), a Rac1 inhibitor, and assessed vascular oxidative stress, expression and activity of involved proteins, endothelial function, macrophage infiltration, and atherosclerosis development. LT-treated wild-type mice displayed decreased vascular NADPH oxidase activity and ROS production. Therapeutic LT doses had no impact on behavior, food intake, body weight, heart rate, blood pressure, vascular and myocardial function, differential blood count, and vascular permeability. ApoE−/− mice were fed a cholesterol-rich diet and were treated with LT or vehicle. LT treatment led to decreased aortic Rac1 GTPase activity, NADPH oxidase activity and ROS production, but had no impact on expression and membrane translocation of NADPH oxidase subunits and RhoA GTPase activity. LT-treated mice showed improved aortic endothelium-dependent vasodilation, attenuated atherosclerotic lesion formation and reduced macrophage infiltration of atherosclerotic plaques. Concomitant treatment of cholesterol-fed ApoE−/− mice with LT, the specific synthetic Rac1 inhibitor NSC 23766 or simvastatin comparably reduced aortic Rac1 activity, NADPH oxidase activity, oxidative stress, endothelial dysfunction, atherosclerosis development, and macrophage infiltration. Conclusions: These findings identify an important role of the small GTPase Rac1 in atherogenesis and provide a potential target for anti-atherosclerotic therapy.