INTRODUÇÃO: Os polimorfismos do gene da proteína priônica (PRNP) podem estar associados a doenças neurológicas não priônicas. Estudos em pacientes com doença de Alzheimer (DA) apontam para possível associação entre os polimorfismos do códon 129 do PRNP e DA. Essa associação não foi estudada na população brasileira. Neste estudo, descrevemos a associação entre os diferentes polimorfismos do PRNP e DA. MÉTODOS: Foi estudada amostra composta por 100 pacientes com DA, acompanhados no Ambulatório de Neurologia Cognitiva e do Comportamento e no Centro de Referência em Distúrbios Cognitivos do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, pareados para grupo controle com 111 indivíduos, em relação à frequência dos diferentes polimorfismos do PRNP e o desempenho cognitivo. Os polimorfismos do PRNP foram estudados pelo método de cromotografia líquida de fase reversa desnaturante (DHPLC). Foi realizada extratificação da amostra pelo genótipo da apolipoproteína E (apoE). RESULTADOS: A frequência dos polimorfismos do códon 129 foi: 45,5% M/M, 42,4% M/V e 12,2% V/V nos pacientes com DA; e 39,6% M/M, 50,5% M/V e 9,9% V/V nos indivíduos controles (p=0,503). O códon 117 apresentou variante alélica silenciosa em 5% dos pacientes com DA e 3% dos controles (p=0,780). A deleção de um ocatapeptídeo repetido ocorreu em 5% dos pacientes com DA e 4% dos controles (p=0,738). Todos os pacientes com DA e os controles eram N171N. Uma paciente do grupo com DA apresentou a mutação V180I. A análise bivariada e regressão logística não mostraram associação entre os diferentes polimorfismos do códon 129 e o desempenho cognitivo nos pacientes com DA, assim como nos indivíduos cognitivamente normais. A extratificação segundo genótipo da apoE não revelou diferença em relação aos polimorfismos do códon 129 do PRNP entre os grupos DA e controles. CONCLUSÕES: Não houve diferença de frequência dos diferentes polimorfismos do códon 129 do PRNP entre os pacientes com DA e idosos cognitivamente normais, bem como em relação aos demais códons polimórficos do gene. Não houve diferença em relação ao desempenho cognitivo nos pacientes com DA e nos controles segundo o polimorfismo do códon 129 do PRNP. Um paciente apresentou mutação do códon 180 (V180I), e recebeu o diagnóstico de doença de Creutzfeldt-Jakob genética / INTRODUCTION: The polymorphism in the prion protein gene (PRNP) may influence non prion neurological diseases. Some reports associate Alzheimers disease (AD) and the polymorphic codon 129 of the PRNP. This association has not been studied in Brazilian population. In this study we aimed to describe the association between the polymorphisms of codon 129 of the PRNP and AD. METHODS: One hundred AD patients were evaluated in the Cognitive and Behavioral Neurology Unit and Cognitive Disorders Reference Center of the Hospital das Clínicas of the University of São Paulo School of Medicine, matched for 111 controls, regarding to the PRNP polymorphism and cognitive measures. The PRNP polymorphisms were analyzed using denaturing high-performance liquid chromatography (DHPLC). Analyzes stratifying by apoE genotype was performed. RESULTS: The distribution of the codon 129 polymorphisms were: 45.5% M/M, 42.4% M/V and 12.2% V/V in AD patients; 39.6% M/M, 50.5% M/V and 9.9% V/V in the control group (p=0.503). The 117 codon analysis revealed silent allelic variant in 5% of AD patients and 3% of controls (p=0.780). The octarepeat deletion occurred in 5% of AD and 4% of controls (p=0.738). All AD patients and controls were N171N. One AD patient had a point mutation at codon 180 (V180I). Logistic regression failed to confirm any association between AD cognitive performance and the codon 129 of PRNP, as well as in the control group. There was no association between the codon 129 genotypes and genotypes and AD according to the apoE stratification. CONCLUSIONS: There were no differences in the frequency of the codon 129 polymorphism between AD. control group, according to the codon 129 polymorphisms. A point mutation at the codon 180 (V180I) was diagnosed in one patient

INTRODUÇÃO: Os polimorfismos do gene da proteína priônica (PRNP) podem estar associados a doenças neurológicas não priônicas. Estudos em pacientes com doença de Alzheimer (DA) apontam para possível associação entre os polimorfismos do códon 129 do PRNP e DA. Essa associação não foi estudada na população brasileira. Neste estudo, descrevemos a associação entre os diferentes polimorfismos do PRNP e DA. MÉTODOS: Foi estudada amostra composta por 100 pacientes com DA, acompanhados no Ambulatório de Neurologia Cognitiva e do Comportamento e no Centro de Referência em Distúrbios Cognitivos do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, pareados para grupo controle com 111 indivíduos, em relação à frequência dos diferentes polimorfismos do PRNP e o desempenho cognitivo. Os polimorfismos do PRNP foram estudados pelo método de cromotografia líquida de fase reversa desnaturante (DHPLC). Foi realizada extratificação da amostra pelo genótipo da apolipoproteína E (apoE). RESULTADOS: A frequência dos polimorfismos do códon 129 foi: 45,5% M/M, 42,4% M/V e 12,2% V/V nos pacientes com DA; e 39,6% M/M, 50,5% M/V e 9,9% V/V nos indivíduos controles (p=0,503). O códon 117 apresentou variante alélica silenciosa em 5% dos pacientes com DA e 3% dos controles (p=0,780). A deleção de um ocatapeptídeo repetido ocorreu em 5% dos pacientes com DA e 4% dos controles (p=0,738). Todos os pacientes com DA e os controles eram N171N. Uma paciente do grupo com DA apresentou a mutação V180I. A análise bivariada e regressão logística não mostraram associação entre os diferentes polimorfismos do códon 129 e o desempenho cognitivo nos pacientes com DA, assim como nos indivíduos cognitivamente normais. A extratificação segundo genótipo da apoE não revelou diferença em relação aos polimorfismos do códon 129 do PRNP entre os grupos DA e controles. CONCLUSÕES: Não houve diferença de frequência dos diferentes polimorfismos do códon 129 do PRNP entre os pacientes com DA e idosos cognitivamente normais, bem como em relação aos demais códons polimórficos do gene. Não houve diferença em relação ao desempenho cognitivo nos pacientes com DA e nos controles segundo o polimorfismo do códon 129 do PRNP. Um paciente apresentou mutação do códon 180 (V180I), e recebeu o diagnóstico de doença de Creutzfeldt-Jakob genética / INTRODUCTION: The polymorphism in the prion protein gene (PRNP) may influence non prion neurological diseases. Some reports associate Alzheimers disease (AD) and the polymorphic codon 129 of the PRNP. This association has not been studied in Brazilian population. In this study we aimed to describe the association between the polymorphisms of codon 129 of the PRNP and AD. METHODS: One hundred AD patients were evaluated in the Cognitive and Behavioral Neurology Unit and Cognitive Disorders Reference Center of the Hospital das Clínicas of the University of São Paulo School of Medicine, matched for 111 controls, regarding to the PRNP polymorphism and cognitive measures. The PRNP polymorphisms were analyzed using denaturing high-performance liquid chromatography (DHPLC). Analyzes stratifying by apoE genotype was performed. RESULTS: The distribution of the codon 129 polymorphisms were: 45.5% M/M, 42.4% M/V and 12.2% V/V in AD patients; 39.6% M/M, 50.5% M/V and 9.9% V/V in the control group (p=0.503). The 117 codon analysis revealed silent allelic variant in 5% of AD patients and 3% of controls (p=0.780). The octarepeat deletion occurred in 5% of AD and 4% of controls (p=0.738). All AD patients and controls were N171N. One AD patient had a point mutation at codon 180 (V180I). Logistic regression failed to confirm any association between AD cognitive performance and the codon 129 of PRNP, as well as in the control group. There was no association between the codon 129 genotypes and genotypes and AD according to the apoE stratification. CONCLUSIONS: There were no differences in the frequency of the codon 129 polymorphism between AD. control group, according to the codon 129 polymorphisms. A point mutation at the codon 180 (V180I) was diagnosed in one patient

<p>Congestive heart failure (CHF) is a major cause of morbidity and mortality and the identification of modifiable risk factors is crucial in order to diminish suffering of this common disease. </p><p>The primary aim of this thesis was to investigate novel metabolic risk factors for CHF, with a focus on insulin resistance and inflammation. The secondary aim was to examine the validity of the CHF diagnosis in the Swedish hospital discharge register.</p><p>This thesis was based on the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, a community-based prospective study started in 1970. The participants were examined at age 50 and 70 and the data was completed with annual updates on mortality and in-hospital morbidity using national registers. </p><p>We showed that insulin resistance predicts CHF incidence independently of established risk factors in both middle-aged and elderly men. The previously described association between obesity and subsequent CHF may be mediated partly by insulin resistance. Moreover, it was established that inflammation, measured as erythrocyte sedimentation rate is a significant predictor of CHF, independent of established risk factors including an interim myocardial infarction. Furthermore, a low beta-carotene level, as well as an increased apolipoprotein B/A-I-ratio was found to predict CHF independently of established risk factors.</p><p>We also showed that the validity of the CHF diagnosis in the Swedish hospital discharge register appears less precise than for other recently investigated cardiovascular diagnoses. However, when including only cases from selected clinics or cases with a primary diagnosis of CHF, the validity is comparable to the above diagnoses. </p><p>In conclusion, insulin resistance and inflammation are strong independent risk factors for the development of CHF, and seem to be involved in the early process leading to CHF. If confirmed, our observations could have large clinical implications as they may offer new approaches in the prevention of CHF.</p>

Congestive heart failure (CHF) is a major cause of morbidity and mortality and the identification of modifiable risk factors is crucial in order to diminish suffering of this common disease. The primary aim of this thesis was to investigate novel metabolic risk factors for CHF, with a focus on insulin resistance and inflammation. The secondary aim was to examine the validity of the CHF diagnosis in the Swedish hospital discharge register. This thesis was based on the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, a community-based prospective study started in 1970. The participants were examined at age 50 and 70 and the data was completed with annual updates on mortality and in-hospital morbidity using national registers. We showed that insulin resistance predicts CHF incidence independently of established risk factors in both middle-aged and elderly men. The previously described association between obesity and subsequent CHF may be mediated partly by insulin resistance. Moreover, it was established that inflammation, measured as erythrocyte sedimentation rate is a significant predictor of CHF, independent of established risk factors including an interim myocardial infarction. Furthermore, a low beta-carotene level, as well as an increased apolipoprotein B/A-I-ratio was found to predict CHF independently of established risk factors. We also showed that the validity of the CHF diagnosis in the Swedish hospital discharge register appears less precise than for other recently investigated cardiovascular diagnoses. However, when including only cases from selected clinics or cases with a primary diagnosis of CHF, the validity is comparable to the above diagnoses. In conclusion, insulin resistance and inflammation are strong independent risk factors for the development of CHF, and seem to be involved in the early process leading to CHF. If confirmed, our observations could have large clinical implications as they may offer new approaches in the prevention of CHF.

At present, cardiovascular diseases cause ca. 30 of deaths worldwide, and are the most common cause of death and disability (The World Health Report 2002; Pearson 1999). Coronary artery disease (CAD) accounts for nearly 50 of all deaths caused by cardiovascular diseases. In 2002, 7.2 million people died of CAD worldwide, and 5.8 million new cases were diagnosed. In 2000, the number of people with CAD around the world amounted to ca. 40 millions (Mackay 2004). The modern understanding of the pathophysiology of atherosclerosis and the concept of “cardiovascular risk factors” started forming in 1950s, when the first findings of the Framingham study were published (Wilson et al. 1998, D’Agostino et al. 2000). Information accumulated during scientific research on atherosclerosis allowed for a significant reduction of CAD-related mortality in the developed countries during the last 20 years, but a more profound analysis showed that the mortality mostly decreased in males, whereas in females it continues to grow. Nearly two-thirds of suddenly deceased women previously showed no clinical symptoms of CAD (AHA 2002). This most probably was influenced by a still predominant erroneous opinion that women, especially of younger age, very rarely have CAD and atherosclerosis of peripheral arteries. Epidemiological studies showed that cardiovascular diseases induced by atherosclerosis are equally frequent cause of death in both males and females. Of all patients who in 2000 in the U.S. died... [to full text]

Proteins modularity enhances the multi-functionality and versatility of proteins by providing such properties as multiple and various ligand-binding sites, increased ligand affinity through the avidity effect, and the juxtaposition of ligand-binding modules near catalytic domains. An NMR-based "dissect-and-build" approach to studying modular protein structure and function has proven very successful, whereby modules are initially characterized individually and then correlated with the overall function of a protein. We have used the dissect-and-build approach and NMR to study two modular protein systems. Chapter 2 details the NMR solution structure of the weak-lysine-binding kringle IV type 8 (KIV8) module from the apolipoprotein(a) (apo(a)) component of lipoprotein(a) was determined and its ligand-binding properties assessed. In vitro studies have demonstrated the importance of the apo(a) KIV7 and KIV8 modules in mediating specific lysine-dependent interactions with the apolipoproteinB-100 (apoB-100) component of LDL in the initial non-covalent step of lipoprotein assembly. Notable differences identified in the lysine binding site (LBS) of the KIV8 were deemed responsible for the differential modes of apoB-100 recognition by KIV7 and KIV8. In addition, the KIV8 structure has brought to light the importance of an RGD sequence at the N-terminus of the apo(a) KIV8 module, which may mediate important apo(a)-integrin interactions. In Chapters 3-6, structure-function studies of the CpGH84C X82 and the CpGH84A dockerin-containing modular pair were conducted to understand how the varying modularity unique to the C-terminal regions of the secreted multi-modular family 84 glycoside hydrolases influences the spreading of Clostridium perfringens. Identification of a CpGH84C cohesin module (X82), and the structural characterization of a dockerin-containing modular pair provides the first evidence for multi-enzyme complex formation mediated by non-cellulosomal cohesin-dockerin interactions. The formation of large hydrolytic enzyme complexes introduces a novel mechanism by which C. perfringens may enhance its role in pathogenesis. / Thesis (Ph.D, Biochemistry) -- Queen's University, 2007-09-27 11:46:38.753

Expansion of visceral adipose tissue correlates with the metabolic syndrome and increased cardiovascular risk. Hypertrophied visceral fat becomes inflamed, causing increased lipolysis, decreased triglyceride storage, and lipotoxicity in skeletal muscle and liver resulting in insulin resistance. Perivascular adipose tissue is a normal component of the adventitia of arteries in humans and animals. Whether or not perivascular adipose also becomes inflamed in obesity is an important question, as this may be an additional, direct mechanism by which obesity causes vascular inflammation and disease. Thus, for the first part of my thesis, we asked the question: does perivascular adipose in mice become inflamed with high fat feeding? In contrast to visceral adipose, macrophage gene expression was not increased in perivascular adipose in response to high fat diet, and this correlated with reduced F480 antigen positive cells as seen by immunohistochemistry and flow cytometry. Interestingly, perivascular adipose surrounding the thoracic aorta was similar to brown adipose tissue, a highly thermogenic fat depot, as shown by histology and DNA microarrays. Moreover, inter-scapular brown adipose was also resistant to diet induced inflammation in comparison to visceral adipose. These findings suggest that brown adipose in the perivascular niche may serve to protect the vasculature from diet induced inflammation, or from cold exposure, or both; whether or not brown perivascular adipose tissue exists in humans has yet to be determined. In the second part of my thesis, we evaluated the role of perivascular adipose tissue in the apolipoprotein E knockout mouse, which exhibits severe hyperlipidemia and atherosclerosis, but is resistant to diet induced obesity and glucose intolerance. We tested the hypothesis that in this model of severe atherosclerosis, inflammation of perivascular adipose does occur. However, we were surprised to find that macrophage specific gene expression, as determined by either microarray analysis or quantitative polymerase chain reaction, was not increased in either the perivascular or the visceral adipose of high fat diet fed apolipoprotein E knockout mice. While the visceral adipose of wild type mice had extensive alterations in gene expression in response to high fat diet, in particular, enrichment of inflammatory gene expression and broad down regulation of peroxisome proliferator activated receptor gamma target genes, apolipoprotein E knockout visceral adipose did not. Importantly, the apolipoprotein E knockout visceral adipose instead showed increased expression of genes encoding enzymes in fatty acid oxidation pathways. High fat diet fed apolipoprotein E knockout visceral adipose was also characterized by smaller adipocyte size. We conclude that, 1) inflammation in thoracic perivascular adipose does not occur in conjunction with diet induced obesity in normal animals nor with atherosclerosis in apolipoprotein E knockout mice, 2) thoracic perivascular adipose tissue is essentially identical to brown adipose tissue in mice, thus potentially protecting the vasculature from the cold, and 3) apolipoprotein E knockout mice remain lean on a high fat diet, despite hyperlipidemia and atherosclerosis, and the decreased adiposity correlates with decreased adipocyte size and adipose inflammation but increased oxidation of fatty acids. Consistent with previous work showing apolipoprotein E controls adipocyte uptake and deposition of triglyceride, its absence prevents adipocyte hypertrophy and resultant inflammation of visceral adipose tissue. Thus limiting adipocyte acquisition of fatty acids may be advantageous, provided that compensatory mechanisms to prevent sustained hyperlipidemia and peripheral organ lipotoxicity can be activated.

Made available in DSpace on 2014-12-17T14:16:25Z (GMT). No. of bitstreams: 1 LuziaLSF_Dissert.pdf: 2090486 bytes, checksum: d33aa3d21b6e7f08dba8853438e95a45 (MD5) Previous issue date: 2009-08-30 / The lipid profile is a group of lab tests that include triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). However, serum non-HDL-C, Apo A-I and Apo B levels, as well as the lipids ratios (TC/HDL-C, LDL-C/HDL-C and Apo B/Apo A-I), have been described as better predictors of cardiovascular diseases. Reference intervals are tools often used to help the evaluation of the people s health state. These days, Brazilian studies still use the reference intervals of lipids and lipoproteins from other countries, ignoring differences between the populations. Therefore, this study aimed to establish reference intervals for lipids, lipoproteins and apolipoproteins in adults of Rio Grande do Norte/Brazil. Healthy individuals (96 men and 283 women) between 18 and 59years old formed the reference sample group. The samples were collected after fasting 12 to 14 hours. Information on lifestyle and dietary habits of the participants were obtained through questionnaire. The serum glucose level and renal and liver activity were evaluated by laboratory testing. The results of lipid profile were analyzed according to sex, age and mesoregion of Rio Grande do Norte, with significance level of 5% (p < 0,05). The lower and upper reference limits were identified by the 2.5 percentile and 97.5 percentile, respectively, and assurance intervals of 90% was calculated for each of these limits. Among the determinants of lipid profile analyzed, only a few significant differences were observed according to sex, but in terms of age, the groups of smaller and older ages were most likely different. When evaluated by region, the means of West region shown the most significant variations. Not many studies were useful to compare the reference intervals determined in this study. Thus, it becomes necessary to carry out similar studies in other regions of Brazil and of the world given the clinical importance of reference intervals / O perfil lip?dico ? definido pelas determina??es laboratoriais dos triglicer?deos, do colesterol total (CT) e das fra??es do colesterol (HDL-C e LDL-C). Por?m, as concentra??es s?ricas do n?o-HDL-C e das apolipoprote?nas A-I e B, assim como as raz?es CT/HDL-C, LDL-C/HDL-C e Apo B/Apo A-I, t?m sido descritos como melhores preditores de doen?as cardiovasculares. Os intervalos de refer?ncia s?o ferramentas frequentemente utilizadas no aux?lio da avalia??o do estado de sa?de das pessoas. Hoje, estudos nacionais ainda utilizam intervalos de refer?ncia do perfil lip?dico procedentes de outros pa?ses, desconsiderando diferen?as entre as popula??es. Assim, este trabalho objetivou estabelecer intervalos de refer?ncia para lip?dios, lipoprote?nas e apolipoprote?nas em adultos no estado do Rio Grande do Norte (RN). Ap?s uma criteriosa sele??o para compor o grupo de refer?ncia de indiv?duos sadios, foram utilizadas 379 amostras de sangue coletadas por venopun??o ap?s jejum de 12 a 14 horas, sendo 96 de homens e 283 de mulheres, ambos com idade entre 18 a 59 anos. Informa??es sobre o estilo de vida e os h?bitos alimentares dos participantes foram obtidas atrav?s de um question?rio e a avalia??o da glicemia e das fun??es renal e hep?tica foi realizada por testes laboratoriais. Os resultados do perfil lip?dico foram analisados em fun??o do sexo, da idade e da mesorregi?o do RN, sempre adotando um n?vel de signific?ncia de 5% (p < 0,05). Os limites de refer?ncia inferior e superior foram identificados atrav?s do percentil 2,5 e do percentil 97,5, respectivamente, e intervalos de confian?a de 90% foram calculados para cada um desses limites. Dentre os determinantes do perfil lip?dico estudados, poucos apresentaram diferen?a significativa quanto ao sexo mas, quanto ? idade, os grupos de menor e maior faixa et?ria foram os que mais diferiram. Quando avaliados por regi?o, os valores m?dios da mesorregi?o Oeste foram os mais diferentes significativamente. Poucos trabalhos foram ?teis para comparar os intervalos de refer?ncia determinados neste estudo. Assim, se faz necess?ria a realiza??o de estudos semelhantes a este em outras regi?es do pa?s e do mundo, visto a grande import?ncia cl?nica dos intervalos de refer?ncia

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-08-17T15:19:39Z No. of bitstreams: 2 Dissertação - Lana Pacheco Franco - 2016.pdf: 2286916 bytes, checksum: 906480e497d4f4ed792e28ce7d57d9b7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-08-17T15:21:10Z (GMT) No. of bitstreams: 2 Dissertação - Lana Pacheco Franco - 2016.pdf: 2286916 bytes, checksum: 906480e497d4f4ed792e28ce7d57d9b7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-08-17T15:21:10Z (GMT). No. of bitstreams: 2 Dissertação - Lana Pacheco Franco - 2016.pdf: 2286916 bytes, checksum: 906480e497d4f4ed792e28ce7d57d9b7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-05-03 / This study aimed to assess whether polymorphisms in the apolipoprotein E gene and food consumption are related to lipid profile of adults with Normal-Weight Obesity Syndrome. Methodology: this was an analytical cross-sectional study, including adults with Normal-Weight Obesity Syndrome. Socioeconomic, health and lifestyle questionnaires were administered. Anthropometric variables, body composition and blood pressure were evaluated. Dietary intake, lipid profile and genotyping of polymorphisms rs7412 and rs429358 in the apolipoprotein E gene were evaluated. Results: from the 115 individuals, 72.2% were women. The median age was 22.6 years (21.4 – 25.2). Only 6.0% of women and no man had increased waist circumference. No women and 6.2% of men had changes in blood pressure. When traditional lipid profile was assessed, 52.5% had dyslipidemia. When apolipoprotein concentrations were included, the prevalence was 73.0%. There was a positive relationship between the presence of allele ε2 and apolipoprotein A1 levels (ε2ε3 versus ε3ε3: β = 21.3; 95% CI = 4.2 to 38.3; p = 0.015) and between ε4 allele and apolipoprotein B (ε4 versus ε2: β = 14.8; 95% CI = 0.08 a 29.5; p = 0.049 and ε4 versus ε3: β = 9.1; 95% CI = 0.6 a 17.6; p = 0.036). Carriers of ε2 allele had 81% less chance of presenting dyslipidemia compared to ε3ε3 individuals (OR = 0.2; 95% CI = 0,04 a 0,8; p = 0.027). Associations between body fat distribution and lipid profile and between food consumption and lipid profile were observed and differed among genotypes. Conclusion: both polymorphisms in the apolipoprotein E gene and the food consumption were associated with lipid profile of adults with Normal-Weight Obese Syndrome. This was the first study to describe the apolipoprotein E genotype and to analyze relationships between genetic profile, food intake and lipid profile of subjects with Normal-Weight Obesity Syndrome. / Avaliar se polimorfismos no gene da apolipoproteína E relacionam-se com consumo alimentar e perfil lipídico de indivíduos adultos com a Síndrome do Obeso Eutrófico. Metodologia: foi realizado estudo transversal analítico, incluindo adultos com Síndrome do Obeso Eutrófico. Foram aplicados questionários socioeconômico, de saúde e estilo de vida e avaliadas variáveis antropométricas, de composição corporal e pressão arterial. Determinou-se o consumo alimentar, o perfil lipídico e o genótipo referente aos polimorfismos rs7412 e rs429358 no gene da apolipoproteína E. Resultados: dos 115 indivíduos avaliados, 72,2% eram mulheres. A mediana de idade foi de 22,6 anos (21,4 – 25,2). Apenas 6,0% das mulheres apresentaram aumento da circunferência da cintura e 6,2% dos homens, alterações na pressão arterial. Quando avaliado o perfil lipídico tradicional, 52,5% dos indivíduos apresentaram dislipidemias. Incluindo-se as concentrações de apolipoproteínas A1 e B, a prevalência foi de 73,0%. O alelo ε2 relacionou-se à maior concentração de apolipoproteína A1 (ε2ε3 versus ε3ε3: β = 21,3 IC 95% = 4,2 a 38,3 p = 0,015) e o alelo ε4, à maior concentração de apolipoproteína B (ε4 versus ε2: β = 14,8 IC 95% = 0,1 a 29,5 p = 0,049 e ε4 versus ε3: β = 9,1 IC 95% = 0,6 a 17,6 p = 0,036). Carreadores do alelo ε2 apresentaram chance 81% menor de desenvolver dislipidemia em comparação aos homozigotos ε3ε3 (OR = 0,2 IC 95% = 0,04 a 0,8 p = 0,027). Associações entre a distribuição da gordura corporal, o consumo alimentar e o perfil lipídico foram observadas e diferiram entre os genótipos. Conclusão: tanto os polimorfismos no gene da apolipoproteína E quanto o consumo alimentar foram associados ao perfil lipídico de adultos com a Síndrome do Obeso Eutrófico. Este foi o primeiro trabalho a descrever o genótipo da apolipoproteína E e a analisar suas relações com consumo alimentar e perfil lipídico nessa população.

Diversos estudos de ressonância magnética (RM) em idosos saudáveis tem avaliado a relação entre envelhecimento, diminuições volumétricas de substância cinzenta (SC) e desempenho cognitivo, usando desenhos de corte transversal e testes de correlação. No entanto, poucos estudos de volumetria baseada em voxel (VBM) tem relatado a diminuição de SC em idosos saudáveis com medições repetidas de RM nos mesmos indivíduos, e nenhum desses estudos longitudinais investigaram a relação entre as mudanças de SC e desempenho cognitivo ao longo do tempo. Além disso, não está claro em achados longitudinais qual a extensão da influência do APOE?4 sobre as reduções de SC em idosos saudáveis. Foram inicialmente avaliados 187 sujeitos idosos (acima de 65 anos) da comunidade, e após 3 anos, uma subamostra de 55 sujeitos realizaram um segundo exame de RM estrutural em equipamento de 1,5 Tesla, bem como reavaliação cognitiva com instrumentos padronizados e validados transculturalmente. Todos os sujeitos foram genotipados para determinar a presença/ausência do alelo APOEe4, bem como a avaliação clínica do grau do risco cardiovascular de acordo com escores de Framingham (FRS). Usando a técnica de VBM, testamos as hipóteses de que: a progressão da perda do desempenho cognitivo está associada a diminuições volumétricas de SC ao longo de 3 anos, envolvendo a região hipocampal e os neocórtices temporal e frontal; e perdas cognitivas associadas à diminuição progressiva de SC cerebral serão maiores em indivíduos com alto risco cardiovascular e em portadores de alelo da APOEe4. Foram encontradas reduções globais e regionais de SC no tálamo direito e giro parahipocampal esquerdo (p < 0,05, family-wise error corrigido para comparações múltiplas por todo o cérebro). Estes resultados não foram afetados pela influência da APOEe4. Foi detectada uma tendência (p=0,093) na correlação entre o grau de declínio cognitivo e redução volumétrica no tálamo direito. Este resultado se manteve quando um coeficiente parcial de correlação foi calculado levando em conta as variações nos escores FRS. Independentemente da APOEe4, as análises longitudinais de VBM mostraram que a região do hipocampo e tálamo são áreas críticas onde a redução de SC e maior que a redução volumétrica global em idosos saudáveis. Os resultados da associação entre a redução de SC no tálamo e a mudança no desempenho cognitivo ao longo do tempo, apoia o recente reconhecimento do papel do tálamo no declínio cognitivo sutil associado ao envelhecimento saudável / A number of magnetic resonance imaging (MRI) studies have investigated the relationship between aging, reduced gray matter (GM) volumes in the brain and cognitive performance, using cross-sectional designs and correlation tests. However, very few VBM studies have documented GM decrements in healthy elderlies with repeated MRI measurements obtained in the same subjects, and none of these longitudinal studies investigated the relationship between GM deficits and changes in cognitive performance over time. Also, it is unclear the extent to which the APOE e4 allele influences on longitudinal findings of GM reductions in healthy elderlies. Were initially evaluated 187 elderly subjects (over 65 years); after 3 years, a sub-sample of 55 individuals underwent a second MRI examination in a 1.5 Tesla equipment, and a cognitive re-evaluation using a structured, transculturally validated neuropsychological battery. All subjects also underwent genotyping for ascertainment of the presence of the APOEe4 allele, as well as clinical assessment of cardiovascular risk according with Framingham scores (FRS). Using voxel-based morphometry (VBM), we will test the following hypotheses: the progression of cognitive decline will be associated with volumetric reductions of GM over three years, involving the hippocampal region and the temporal and frontal neocortices; cognitive decline associated with progressive GM volume reductions will be greater in individuals with higher cardiovascular risk and carriers of the APOE?4 allele. We found global GM reductions as well as regional GM decrements that were significant in the right thalamus and left parahippocampal gyrus (p < 0.05, family-wise error corrected for multiple comparisons over the whole brain). These findings were not affected by APOE e4. A trend correlation (p=0.093) was detected between the degree of cognitive decline over time and right thalamic volume shrinkage. This finding retained statistical significance when a partial coefficient of correlation was calculated taking into account variations in FRS scores. Irrespective of APOEe4, longitudinal VBM analyses show that the hippocampal region and thalamus are critical sites where GM shrinkage is significantly greater than the degree of global brain volume reduction in healthy elders. The trend towards an association between thalamic GM decrement and cognitive performance change over time supports the recently recognized role of the thalamus in the subtle cognitive decline associated with healthy human aging