Objectives: This thesis examines the risks among Canadian children and adolescents for developing cardio-metabolic diseases, extending evidence that is well-established for adults to pediatric populations. As well, novel indicators and cut-offs for the measurements of disease risks are proposed and associations between physical activity, weight status, socio-economic status and cardio-metabolic health are examined. Methodology: Secondary data analysis was conducted using data from three cycles of the Canadian Health Measures Survey (CHMS), a nationally representative data set which includes measured anthropometric characteristics. A population health approach was applied throughout, underpinned by the World Health Organization’s Conceptual Framework for Action on the Social Determinants of Health. The thesis was designed such that a series of four manuscripts successively built on the key findings from each previous research paper: 1. Establishing the prevalence of Metabolic Syndrome and its risk factors for 10-18 year olds using the International Diabetes Federation child, adolescent and adult definitions. 2. Estimating pre-obesity epidemic waist circumference reference values for Canadian children 6-10 years using reference data from the 1981 Canada Fitness Survey, the Third National Health and Nutrition Examination Survey (1988-1994), and the CHMS through regression of linear, logarithmic and quadratic functions. This work facilitated an expanded age range for the subsequent projects as age- and sex-specific cut-offs based on a Canadian population prior to the obesity epidemic had not been available. 3. Cardio-metabolic risk by body mass index (BMI), waist circumference (WC), and a combined BMI-WC indicator quantified the associations between a dichotomous cardio-metabolic risk variable, and obesity, using three indicators of obesity including a novel indicator, for ages 6-18 years. 4. Association between cardio-metabolic risk and inflammation quantified the associations between inflammation, using high-sensitivity c-reactive protein (CRP) as a marker, and cardio-metabolic risk to determine if high CRP was a significant predictor of cardiometabolic risk among 6-18 year olds. Results: For Paper 1 (n=1228), only 2.1% were classified as having the Mets though 38% had at least 1 MetS risk factor. For Paper 2, logarithmic regression predicted WC cut-offs with the lowest degree of error. For Paper 3 (n=2678), 35% were classified as having cardio-metabolic risk with significantly higher levels among those classified as obese and/or having a low level of physical activity. All indicators of obesity had significant associations with cardio-metabolic risk. For Paper 4 (n=1831), 43.6% of children and 62.0% of adolescents with high CRP levels were classified as having cardio-metabolic risk, a significant relationship. Participants from households with moderate to high income and/or education had the lowest prevalence of MetS risk factors and abdominal obesity. Conclusions: High CRP is a useful indicator of cardio-metabolic risk for pediatric populations. With further research, novel combinations of BMI and WC may be shown to be more predictive for cardio-metabolic risk than these indicators individually. The substantial prevalence of multiple risk factors which predict premature onset of chronic disease foreshadows potential years of morbidity in adulthood for Canada’s youth population.

L’arthrose, maladie articulaire la plus fréquente, se décline en plusieurs phénotypes selon les facteurs de risque : vieillissement, traumatisme et obésité. Dans l’arthrose liée à l’obésité il existe une origine mécanique mais aussi systémique faisant intervenir les adipokines. De plus, chez les sujets obèses, la présence d’un syndrome métabolique, et singulièrement un diabète de type 2 augmente fortement le risque d’arthrose. L’objectif de ce travail a été d’étudier les rôles d’une adipokine, la visfatine/Nampt (nicotinamide phosphoribosyltransférase), et de l’hyperglucidie dans l’arthrose. Ainsi, la visfatine est produite et libérée sous forme dimérique par l’ensemble des tissus articulaires, et son activité enzymatique Nampt est présente dans le tissu synovial. Elle induit un profil pro-inflammatoire des chondrocytes et des ostéoblastes murins caractérisé par la production de cytokines (IL-6, IL -8, MCP-1) qui implique en partie l’activité Nampt, démontré par utilisation de l’inhibiteur pharmacologique APO866. Sur chondrocytes murins, l’hyperglucidie potentialise l’effet de l’IL-1β sur l’activation pro-inflammatoire (IL-6, PGE2), sans stress osmotique. Cette potentialisation pro-inflammatoire passe par l’activation de la voie alternative des polyols, ainsi que par un stress oxydant, démontré par utilisation de l’inhibiteur de l’aldose réductase (epalrestat) et de deux antioxydants (Mitotempo et L-NAME). Chez l’Homme, le cartilage issu de patients arthrosiques diabétiques est plus sensible à l’IL-1β (libération d’IL-6 et de PGE2) et exprime plus l’AGE carboxyméthyllysine, que celui issu de patients non diabétiques de même âge et poids. / Osteoarthritis,the most frequent joint disease, can be declined in different phenotypes, depending on its risk factors: aging, trauma and obesity. In obesity-linked osteoarthritis, there is a mechanical stress but also a systemic stress involving adipokines. Moreover, in obese patients, a metabolic syndrome, and particularly a type 2 diabetes, increases the risk of developing osteoarthritis. The aims of the thesis were to study the roles of the adipokine visfatin/Nampt (nicotinamide phosphoribosyltransferase) et high glucose in osteoarthritis. Then, we demonstrate that visfatin is produced and released in an enzymatic dimeric form by all the articular tissues and that its enzymatic activity Nampt is present in synovium. Visfatin/Nampt induces a pro-inflammatory phenotype of murine chondrocytes and osteoblasts characterized by the production of cytokines (IL-6, IL-8, MCP-1), involving in part the enzymatic activity Nampt, demonstrated by using the pharmacological inhibitor APO866. On murine chondrocytes, high glucose potentiates the effect of IL-1β on pro-inflammatory activation (IL-6, PGE2), without inducing an osmotic stress. This potentiation involves the alternative polyol pathway and oxidative stress, demonstrated by using an inhibitor of aldose reductase (epalrestat) and two antioxidants (Mitotempo and L-NAME). In human, the cartilage from osteoarthritic diabetic patients is more sensitive to IL-1β (release of IL-6 and PGE2) and expresses more the AGE carboxymethyllysine than the one from non diabetic patients, of same age and weight.

L’hypertension artérielle (HTA) est considérée comme un facteur de risque modifiable de démence. Dans ce contexte, nous nous sommes intéressés à différents aspects du traitement de l’HTA indépendamment de la réduction de pression artérielle : d’une part aux effets des différentes classes d’antihypertenseurs sur le déclin cognitif et l’incidence de démence, en réalisant une méta-analyse en réseau ; et, d’autre part, sur la variabilité depression artérielle (PA), qui pourrait être impliquée dans la relation délétère entre l’HTA et la cognition, à partir d’une cohorte de sujets hypertendus traités. Nous avons également étudié le rôle de l’HTA dans la relation entre le syndrome métabolique et les troubles cognitifs, à partir d’une cohorte de patients avec facteurs de risque vasculaires. Nos résultats confirment la prévention de démence avec les antihypertenseurs et soutiennent l’hypothèse de bénéfices cognitifs supérieurs avec les antagonistes des récepteurs de l’angiotensine II par rapport aux autres classes d’antihypertenseurs, mais, ils suggèrent que la variabilité de pression artérielle ne constitue pas un mécanisme principal à l’origine de ces différences, puisque les inhibiteurs calciques offrent la meilleure réduction de variabilité de PA. Nos résultats ne supportent pas le rôle du syndrome métabolique en tant que tel dans le déclin cognitif, mais de celui de l’HTA et du diabète. L’ensemble de ces résultats démontrent qu’une approche multifactorielle doit être considérée dans le traitement de l’HTA, et offrent des perspectives dans le choix du traitement antihypertenseur pour prévenir le fardeau de la démence. / Hypertension is considered a modifiable risk factor of dementia. In this context, we studied different aspects of the treatment of hypertension independantly from the blood pressure reduction. We compared the effects of the different antihypertensive drug classes, on cognitive decline and incidence of dementia in a network meta-analysis on the one hand, and on short-term blood pressure variability, which is suspected to be related to cognitive decline,in a cohort of treated hypertensive patients, on the other hand. We also studied the contribution of hypertension in the relationship between metabolic syndrome and cognitive impairment, in a cohort of patients with vascular risk factors. Our results confirmed the benefits of antihypertensive treatment in the prevention of incident dementia, and support the hypothesis of superior benefits with angiotensin receptor blockers compared to the other drug classes. Our finding of calcium channel blockers being the class providing the lowest blood pressure variability does not support blood pressure variability being a primary mechanism involved in the differential effects of antihypertensive drug classes on cognition. We demonstrated that hypertension and diabetes, rather thanmetabolic syndrome in itself, were related to cognitive impairment. Overall, our results highlight the need to consider a multifactorial approach in hypertensiontreatment, and provide perspectives regarding the choice of antihypertensive treatment to prevent the burden of dementia.

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.

Orientador: Jean Leandro dos Santos / Banca: José Luiz Riani Costa / Banca: Ricardo Radhiguieri Rascado / Resumo:A Síndrome Metabólica é um conjunto de fatores de risco para o desenvolvimento de doenças cardiovasculares e diabetes mellitus 2. No Brasil, estudos relatam que a prevalência de síndrome metabólica varia entre 30% e 45% da população. Tal panorama demonstra a necessidade de desenvolver novas abordagens de cuidado em saúde, principalmente na Atenção Básica, para prevenir, detectar e tratar complicações decorrentes deste problema. O objetivo deste trabalho foi desenvolver e aplicar um modelo de acompanhamento farmacoterapêutico em pacientes idosos diagnosticados com síndrome metabólica e usuários da Estratégia Saúde da Família (ESF), a fim de controlar os parâmetros bioquímicos e fisiológicos, e prevenir o aparecimento de comorbidades. Neste estudo clínico prospectivo, realizado entre novembro de 2013 e junho de 2014, foram acompanhados 55 idosos divididos em dois grupos. O grupo controle (28) recebeu o cuidado da equipe da ESF enquanto o grupo intervenção (27), além da ESF, teve acompanhamento farmacêutico. Foram avaliados antes e depois do seguimento farmacoterapêutico os Problemas Relacionados com Medicamento (PRM), a adesão à terapia medicamentosa, a pressão arterial, o colesterol total, os triglicérides, a glicemia em jejum e a circunferência abdominal. Os encontros com o usuário se deram ao longo de seis meses. No grupo intervenção, a pressão arterial sistólica e a diastólica sofreram redução significativa: -13 mmHg e -6mmHg respectivamente; a circunferência abdominal reduziu de 109,3 cm para 106,9 cm nas mulheres e de 108,6 cm para 106 cm nos homens (p<0,05). O colesterol total não sofreu alteração significativa no GI, entretanto aumentou no GC de 183 mg/dL para 211 mg/dL (p<0,05). No início do acompanhamento, apenas 10 pacientes do GI apresentavam adesão à terapia medicamentosa e... / Abstract: Metabolic Syndrome is a cluster of risk factors for developing cardiovascular disease and type 2 diabetes. In Brazil, studies have reported that prevalence of the metabolic syndrome varies between 30% and 45% of the population. This scenario demonstrates the need to develop new health care approaches, especially in primary care to prevent, detect and treat complications of metabolic syndrome. The objective of this study was to develop and accomplish a pharmaceutical care model to elderly patients with metabolic syndrome users of the Family Health Strategy (FHS) in order to monitor the biochemical and physiological parameters, and prevent comorbidities. In this prospective clinical study conducted between November 2013 and June 2014, 55 elderly were investigated and divided into two groups. The control group (28) received the traditional care while the intervention group (27), in addition to the traditional care, had pharmaceutical care. Drug Related Problems (DRPs) were evaluated before and after pharmaceutical care. Adherence to drug therapy, blood pressure, cholesterol, triglycerides, fasting glucose and waist circumference were also evaluated. The meetings with patient took place monthly over six months. In the intervention group, systolic blood pressure was significantly reduced by 13 mmHg and diastolic by 6 mmHg and abdominal circumference decreased from 109,3 cm to 106,9 cm for women and 108,6 cm to 106 cm in men (p <0.05). Total cholesterol did not change significantly in IG, however increased in CG from 183 mg / dL to 211 mg / dL (p <0.05). At the beginning of follow-up, only 10 patients were considered adherent to drug therapy and at the end, 17 adhered to therapy (p<0,05). The most prevalent DRPs were lack of adherence to treatment and need of additional medication. It was detected 68 Drug Related Problems, of which 50 (74%) were ... / Mestre

Orientadores: Denise Engelbrecht Zantut Wittmann, Heraldo Mendes Garmes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T18:57:15Z (GMT). No. of bitstreams: 1 RosellCastillo_Alejandro_M.pdf: 1638622 bytes, checksum: 1b3c715bebcd9913f573b5ef8758046e (MD5) Previous issue date: 2015 / Resumo: Introdução O Hipopituitarismo (HP) é uma doença que tem como condição básica a deficiência na produção ou na ação de qualquer um dos hormônios da adeno-hipófise. Quando isto ocorre em dois ou mais hormônios, é denominado Pan-hipopituitarismo (PH). O HP é conhecidamente associado ao aumento da prevalência de Síndrome metabólica (SM), principalmente em pacientes com deficiência grave de hormônio de crescimento (GH). Apesar da suposta relação entre HP e síndrome metabólica, poucos estudos avaliaram a prevalência da SM e suas características clínico-laboratoriais nos pacientes com PH, geralmente ressaltando apenas a relação com a falência de GH. Objetivos Neste sentido, devido à escassez de informações na literatura, realizamos um estudo em pacientes com Pan-hipopituitarismo investigando as características e as frequências da SM e esteatose hepática (EH), assim como os perfis glicêmico, lipídico e de marcadores inflamatórios e de RI comparados a um grupo controle pareados pela idade, sexo e IMC. Metodologia Estudo transversal em que foram avaliados 41 pacientes com diagnóstico de PH e 37 indivíduos com função hipofisária normal pareados pela idade, sexo e índice de massa corporal. Avaliaram-se dados clínicos, antropométricos, ultrassonográficos (para EH), concentrações séricas de proteína C reativa (PCR) bem como exames laboratoriais que refletem os perfis lipídico, glicêmico e de RI. Resultados As frequências de SM e EH foram 65,9% e 78% nos pacientes com PH, e de 59,5% e 64,9% nos indivíduos do grupo de controle respetivamente. No entanto a frequência do diagnostico de dislipidemia (DLP) foi maior nos pacientes com PH (75,6% vs 51,4%; p=0,026). Os valores de Índice cintura quadril (ICQ) (p<0,001), glicemia (Gli) (p=0,010), insulina (p<0,001), e do índice indicativo de resistência à insulina (Homeostatic Model Assessment, HOMA-IR) (p<0,001) foram maiores nos indivíduos do grupo de controle. Por outro lado as concentrações séricas de PCR (p=0,011) foram maiores nos pacientes com PH. Na comparação entre os pacientes e indivíduos controle com SM, apresentaram-se valores significativamente superiores no grupo de indivíduos com SM, em relação à Gli (p=0,043), hemoglobina glicada (HBGli) (p=0,030), insulina (p<0,001), HOMA-IR (p<0,001), ICQ ( p=0,001). No entanto, os pacientes com PH e SM apresentaram maior frequência do diagnóstico de DLP (P=0,012) e concentrações significativamente superiores de PCR (P=0,028). O índice de massa corporal (IMC), idade e sexo feminino foram fatores de risco independentes para o desenvolvimento de SM nos pacientes com pan-hipopituitarismo, e a hemoglobina glicada nos indivíduos do grupo controle. Conclusões As frequências de síndrome metabólica e esteatose hepática foram semelhantes em pacientes com PH e nos indivíduos controle, por outro lado a frequência do diagnóstico de DLP foi maior nos pacientes com PH. Os indivíduos controle com SM apresentaram maior RI quando comparados aos pacientes com PH e SM. No entanto, os pacientes com PH e SM apresentaram maiores concentrações de PCR, e maior frequência do diagnóstico de DLP. O IMC, idade e sexo feminino foram os fatores de risco independentes para o desenvolvimento da SM nos pacientes com PH e a hemoglobina glicada nos indivíduos do grupo de controle / Abstract: Introduction Hypopituitarism (HP) is a disease that is characterized by the deficiency in secretion or action of any of the anterior pituitary hormones. When it occurs in two or more hormonal axis it is denominated pan-hypopituitarism (PH). PH is associated to and increased prevalence of metabolic syndrome (MS), especially in patients with severe growth hormone (GH) deficiency. Despite the supposed relation of MS and PH, few studies have assessed the prevalence of MS and its clinical and laboratorial characteristics in patients with PH, often only highlighting the association with GH deficiency. Objectives Thus, due to the paucity of information in the literature, we conducted a study in patients with PH investigating the characteristics and the frequencies of MS and hepatic steatosis (HS), as well as fasting glycaemia, lipid profile and inflammatory and insulin resistance markers compared to a control group paired by age, sex and body mass index (BMI). Methodology This was a cross study evaluating 41 patients with PH and 37 individuals with normal pituitary function paired by age, sex and BMI. We evaluated clinical, anthropometric and ultrassonographic (for HS) data as well as serum levels of C-reactive protein (CRP), fasting glycaemia, lipid profile and insulin resistance index. Results The frequencies of MS and HS were 65.9% and 78% in patients with PH and 59.5% and 64.9% in control group individuals, respectively. However, the frequency of dyslipidemia diagnosis was higher in patients with PH (75.6% vs 51.4%; p=0.026). Waist to hip ratio (WHR) (p<0.001), fasting glycemia (p=0.01), fasting insulin (p<0.001) and the HOMA (Homeostatic Model Assessment ¿ HOMA IR) (p<0.001) were higher in control group individuals. On the other hand, CRP (p=0.011) levels were higher in patients with PH. Comparing control group individuals with MS and patients with PH and MS, fasting glycaemia (p=0.043), HbA1c (p=0.03), fasting insulin (p<0.001), HOMA IR (p<0.001) and WHR (p=0.001) were higher in the control group. Patients with PH and MS presented higher frequency of dyslipidemia diagnosis (p=0.012) and CRP levels (p=0.028). Body mass index, age and female sex were independent risk factors for MS in patients with PH, whereas the only significant factor in the control group was HbA1c. Conclusions The frequencies of MS and HS were similar in patients with PH and control group individuals. However, the frequency of dyslipidemia was higher in patients with PH. Control group individuals with MS showed increased insulin resistance when compared to patients with PH and MS. Patients with PH and MS had higher serum concentrations of CRP, and higher frequency of dyslipidemia diagnosis. Body mass index, age and female sex were independent risk factors for MS development in patients with PH whereas only HbA1c was a significant risk factor for MS in control group individuals / Mestrado / Clinica Medica / Mestre em Clinica Medica

Orientadores: Lúcia Helena Simões da Costa Paiva, Ana Lúcia Ribeiro Valadares / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T21:45:11Z (GMT). No. of bitstreams: 1 Akl_LiviaDrumond_D.pdf: 1659743 bytes, checksum: 05cc93759e4280105f72769b37386da1 (MD5) Previous issue date: 2015 / Resumo: A terapia antirretroviral (TARV) impactou drasticamente na taxa mortalidade e expectativa de vida de pessoas vivendo com HIV (PVHS), mas tem sido associada a uma série de alterações metabólicas, incluindo a síndrome metabólica (SM). Tal como para as consequências clínicas da SM, existe evidência de que as mulheres são particularmente afetadas negativamente. Objetivos: Determinar a prevalência de SM e fatores associados em mulheres climatéricas com e sem o vírus da imunodeficiência humana (HIV). Métodos: Realizou-se um estudo de corte transversal, entre outubro de 2010 e julho de 2012, em uma amostra com 537 mulheres (273 mulheres climatéricas HIV soropositivas e 264 mulheres climatéricas HIV soronegativas) entre 40 e 60 anos em dois centros de referência no tratamento ambulatorial de HIV. A SM foi diagnosticada de acordo com o critério da IDF, 2006. Foi realizada uma entrevista para avaliação dos fatores sociodemográficos, clínicos, comportamentais e fatores associados com a infecção pelo HIV. Todas foram submetidas à medida do peso corporal, altura, circunferência da cintura, pressão arterial e realizaram coleta de sangue periférico para dosagem de colesterol total e frações, triglicérides, glicemia de jejum e dosagens hormonais. Foram utilizadas a análise bivariada e a análise de regressão múltipla para selecionar os principais fatores associados à SM. Resultados: A média de idade foi de 47,7 anos nas mulheres HIV soropositivas e 49,8 anos nas mulheres HIV soronegativas (p<0,001). A prevalência de SM no grupo soropositivo foi de 46,9% em comparação com 42,2% no grupo soronegativo (p=0,340). A análise bivariada mostrou maior prevalência de SM no grupo HIV soropositivo em mulheres que estavam na pós-menopausa em comparação ao grupo soronegativo (p=0,032), em uso de terapia hormonal (TH) (p=0,040), quando a autopercepção de saúde foi considerada excelente/boa (p=0,011) e em mulheres com índice de massa corporal (IMC) > 25 kg/m² (p=0,005). A análise bivariada somente do grupo HIV soropositivo mostrou associação entre SM e idade ? 50 anos (p=0,002), escolaridade < 8 anos (p=0,003), pós-menopausa (p<0,001), IMC > 25 Kg/m² (p<0,001) e FSH ? 40 mUI/mL (p=0,002). Não houve associação entre SM e o uso de Lopinavir e Indinavir no grupo HIV soropositivo. A análise de regressão múltipla no grupo geral mostrou que os fatores associados a SM foram IMC > 25 kg/m² (RP: 2,34; IC95%%: 1,70-3,21; p<0,001), envelhecimento (RP: 1,05; IC95%%: 1,02-1,07; p<0,001) e uso de TARV (RP: 1,48; IC95%%: 1,13-1,94; p=0,005). A análise múltipla somente do grupo soropositivo mostrou associação entre SM e IMC em kg/m² (RP: 1,09; IC95%%: 1,05-1,13; p<0,001) e dosagem de hormônio folículo estimulante (FSH) ? 40 mUI/mL (RP: 1,66; IC95%%: 1,14-2,40; p=0,008). Conclusão: Não houve associação de SM e infecção pelo HIV. Verificou-se que as mulheres HIV soropositivas tiveram prevalência significativamente maior de SM quando na pós-menopausa, com alto IMC e em uso da TARV. Observa-se a necessidade de uma melhor abordagem de mulheres HIV soropositivas e soronegativas para evitar o ganho de peso e SM / Abstract: Antiretroviral therapy (ART) dramatically impacted mortality and life expectancy in people living with HIV (PLWH), but has been associated with a number of metabolic abnormalities, including metabolic syndrome (MetS). As to the clinical consequences of MetS, there is evidence that females are particularly negatively affected. Objectives: To determine the prevalence of MetS and associated factors in climacteric women with and without human immunodeficiency virus (HIV). Methods: A cross-sectional study between october 2010 and july 2012, in a sample of 537 women (273 HIV seropositive climacteric women and 264 HIV seronegative climacteric women) between 40 and 60 years at two referral centers in the HIV outpatient¿s clinic. MetS was diagnosed according to IDF, 2006. Interviews to assess sociodemographic, clinical, and behavioral factors associated with HIV infection was performed. All women were submitted to body weight, height, waist circumference, blood pressure and performed peripheral blood collection for total cholesterol dosage and fractions, triglycerides, fasting glucose and hormone levels. Bivariate analysis and multiple regression analysis to select the main factors associated with MetS were performed. Results: The mean age was 47.7 years in HIV seropositive women and 49.8 years in the HIV seronegative women (p<0.001). The prevalence of MetS in HIV seropositive climacteric women was 46.9% compared to 42.2% in the HIV seronegative group (p=0.340). Bivariate analysis revealed a higher prevalence of MetS in HIV seropositive group in women who were postmenopausal compared to HIV seronegative group (p=0.032), in use of hormone therapy (HT) (p=0.040), when the self-rated health was considered excellent/good (p=0.011) and in women with body mass index (BMI) > 25 kg/m² (p=0.005). The bivariate analysis of such HIV seropositive group showed an association between MetS and age ? 50 years (p=0.002), formal education < 8 years (p = 0.003), being postmenopausal (p<0.001), BMI > 25 kg/m² (p<0.001) and FSH ? 40 mIU/mL (p=0.002). There was no association between MetS and the use of Lopinavir and Indinavir in HIV seropositive group. Multiple regression analysis showed that in the whole group, factors associated with MetS were BMI > 25 kg/m² (PR: 2.34; 95 % CI: 1.70 to 3.21; p<0.001), aging (PR: 1.05; 95 % CI: 1.02 to 1.07; p<0.001) and the use of HAART (PR: 1.48; 95 % CI: 1.13 to 1.94; p = 0.005). Multiple analysis of such HIV seropositive group showed an association between MetS and BMI in kg/m² (PR: 1.09; 95 % CI: 1.05-1.13; p<0.001) and follicle stimulating hormone dosage (FSH) ? 40 mIU/mL (PR: 1.66; 95 % CI: 1.14 to 2.40; p=0.008). Conclusion: There was no association of MetS and HIV infection. It was found that HIV seropositive women had significantly higher prevalence of MetS when being postmenopausal, with high BMI and in use of HAART. There is a need of a better approach to both HIV seropositive and seronegative women to prevent weight gain and MetS / Doutorado / Fisiopatologia Ginecológica / Doutora em Ciências da Saúde

Crescem a cada dia os índices globais de obesidade associada à síndrome metabólica (SM) e à inflamação. Sob este aspecto, os compostos fenólicos (CFs) exercem papel importante, especialmente no que diz respeito às suas propriedades anti-inflamatória e antiobesogênica. A jabuticaba Sabará (Myrciaria jaboticaba (Vell.) Berg) é uma fruta nativa bem aceita pelos brasileiros e rica em CFs. O objetivo deste trabalho foi avaliar o efeito da administração diária de extratos ricos em CFs desta fruta a camundongos C57BL/6, alimentados com dieta hiperlipídica com alto teor de sacarose (HFHS) por 8 semanas. Os extratos ricos em CFs foram obtidos por extração do fruto inteiro em solução metanol/água (80:20, v/v), seguida de rotaevaporação e extração em fase sólida (EFS). Os animais foram distribuídos em 5 grupos: o grupo Padrão recebeu dieta padrão de laboratório e veículo (água) por gavagem, o grupo HFHS recebeu dieta HFHS e veículo, o grupo EB recebeu 200 mg b. s. (base seca)/kg de peso corporal (PC) de extrato bruto (EB), o grupo C18 recebeu 50 mg EAG (equivalentes de ácido gálico)/kg de PC do extrato obtido em sorvente octadecil silano (C18) (que permite a obtenção de todos os CFs da fruta) e o grupo PA recebeu 50 mg EAG/kg de PC do extrato obtido em sorvente poliamida (PA) (que permite a obtenção de todos os CFs da fruta, exceto os elagitaninos). O grupo C18 apresentou menores ganho de peso, adiposidade e eficiência energética, comparado ao grupo HFHS. Já o grupo EB teve menor expressão gênica do fator de necrose tumoral alfa (TNF-&#945;) no tecido adiposo branco epididimal, e menor concentração deste mesmo marcador no fígado. Estes resultados sugerem que os elagitaninos têm um papel importante na redução do risco do desenvolvimento de obesidade em camundongos que receberam dieta indutora de obesidade e SM, enquanto o EB da fruta parece contribuir para a redução da inflamação destes animais, porém os mecanismos para tal ainda não estão esclarecidos. / The incidence of obesity is increasing associated with other disorders as metabolic syndrome (MS) and low-grade inflammation. Phenolic compounds (PC) have some well-known properties, such as anti-inflammatory, antidiabetic and antiobesity capacities. Jaboticaba Sabará (Myrciaria jaboticaba (Vell.) Berg) is a brazilian fruit well accepted in this country and it has a high PCs amount. The aim of this study was to investigate the effects of phenolic-rich jaboticaba extracts in C57Bl/6J mice fed a high fat/high sucrose (HF/HS) diet during 8 weeks. The phenolic-rich jaboticaba extracts were prepared from fruit extraction in methanol/water solution (80:20, v/v), followed by rotary evaporation and solid phase extraction (SPE). The mice were distributed in 5 groups: the Chow group was fed a chow diet and gavaged daily with vehicle (water), the HFHS group was fed a HF/HS diet vehicle as well, the CE group received 200 mg of jaboticaba crude extract (CE)/kg body weight (BW), the C18 group received 50 mg AGE (acid galic equivalent)/kg BW of phenolic-rich jaboticaba extract obtained by octadecyl silane (C18) sorbent (which permits to extract every PCs from the fruit) and the PA group were gavaged with 50 mg AGE/kg BW of this fruit extract obtained by polyamide (PA) sorbent (which allows to extract every PCs from jaboticaba, excepting ellagitannins). The C18 group had the lowest BW gain, adiposity and energy efficiency, compared to the HFHS group. The CE group presented low tumor necrose factor-&#945; (TNF-&#945;) gene expression on epididymal white adipose tissue and it had also a low hepatic concentration of this inflammatory marker, compared to HFHS group. These results suggest ellagitannins has an important role on reducing risk of obesity in HF/HS-fed mice, while jaboticaba CE seems to contribute on reduction of inflammation in these animals, but the mechanisms are still not understood.

abstract: According to the World Health Organization, obesity has nearly tripled since 1975 and forty-one million children under the age of 5 are overweight or obese (World Health Organization, 2018). Exercise is a potential intervention to prevent obesity-induced cardiovascular complications as exercise training has been shown to aid nitric oxide (NO) production as well as preserving endothelial function in obese mice (Silva et al., 2016). A soil-derived organic mineral compound (OMC) has been shown to lower blood sugar in diabetic mice (Deneau et al., 2011). Prior research has shown that, while OMC did not prevent high fat diet (HFD)-induced increases in body fat in male Sprague-Dawley rats, it was effective at preventing HFD-induced impaired vasodilation (M. S. Crawford et al., 2019). Six-weeks of HFD has been shown to impair vasodilation through oxidative-stress mediated scavenging of NO as well as upregulation of inflammatory pathways including inducible nitric oxide synthase (iNOS) and cyclooxygenase (Karen L. Sweazea et al., 2010). Therefore, the aim of the present study was to determine whether OMC alters protein expression of iNOS and endothelial NOS (eNOS) in the vasculature of rats fed a control or HFD with and without OMC supplementation. Six-week old male Sprague-Dawley rats were fed either a standard chow diet (CHOW) or a HFD composed of 60% kcal from fat for 10 weeks. The rats were administered OMC at doses of 0 mg/mL (control), 0.6 mg/mL, or 3.0 mg/mL added to their drinking water. Following euthanasia with sodium pentobarbital (200 mg/kg, i.p.), mesenteric arteries and the surrounding perivascular adipose tissue were isolated and prepared for Western Blot analyses. Mesenteric arteries from HFD rats had more uncoupled eNOS (p = 0.006) and iNOS protein expression (p = 0.027) than rats fed the control diet. OMC was not effective at preventing the uncoupling of eNOS or increase in iNOS induced by HFD. Perivascular adipose tissue (PVAT) showed no significant difference in iNOS protein expression between diet or OMC treatment groups. These findings suggest that OMC is not likely working through the iNOS or eNOS pathways to improve vasodilation in these rats, but rather, appears to be working through another mechanism. / Dissertation/Thesis / Masters Thesis Biology 2020

Dans cette thèse, nous avons étudié la relation entre le traitement par antidépresseurs, la prise du poids et le syndrome métabolique sur un échantillon de patients atteints de TDM. Les résultats cliniques ont suggéré que la prise du poids précoce due au traitement par antidépresseurs augmenterait le risque de prise du poids ultérieure et d’incidence ultérieure du syndrome métabolique. Ainsi que la relation entre l'utilisation des antidépresseurs, la réponse au traitement et la prise du poids reste complexe. Malgré l'augmentation simultanée de la consommation d'antidépresseurs et la tendance à l'obésité dans les sociétés occidentales, des cohortes prospectives supplémentaires sont nécessaires pour tester pleinement l'hypothèse traitant que la prise du poids chez les utilisateurs des antidépresseurs est un effet iatrogène. Bien que l'impact des antidépresseurs sur la morbidité cardiovasculaire ne puisse toujours pas être déterminé, les résultats du premier chapitre ont montré que l'utilisation des antidépresseurs, indépendamment de leurs classes, avait un impact sur les dérèglements métaboliques, nécessitant une attention clinique spécifique. Une étude de cohorte à long terme est nécessaire pour confirmer si l'interruption et la réinstauration du traitement par des antidépresseurs seraient liées à la fluctuation des dysrégulations du syndrome métabolique. / In this dissertation we have studied the relationship between AD treatment, weight gain and MetS on a sample of MDD patients. Clinical findings have suggested that early weight gain due to AD treatment would increase the risk of both later weight gain and later MetS incidence. The relationship between AD use, response to treatment and weight gain remain complex. Despite the simultaneous increase in AD use and obesity trends in Western societies, additional prospective cohorts are needed to fully test the hypothesis that weight gain among AD users is indeed an iatrogenic effect. Although impact of AD on cardiovascular morbidity still cannot be ascertained, the results from the first chapter showed that AD use – irrespective of the class - does impact and worsen metabolic dysregulations, which would require specific clinical attention. A long term cohort study is required to confirm whether discontinuation and re-initiation of AD treatment would be linked to fluctuation in MetS dysregulations.