Níveis sanguíneos totais de microrRNAs em pacientes portadores e não portadores da demência de Alzheimer provável

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, 2019Introdução: Evidências recentes sugerem que alterações nos níveis de microRNA circulante podem ser biomarcadores promissores para o diagnóstico clínico da doença de Alzheimer (DA). Hipotetizamos que os microRNAs (miRNAs) do sangue total podem ser úteis na identificação de indivíduos com DA. Objetivo: Comparar níveis de um grupo selecionado de miRNAs circulantes a partir do sangue total de mulheres acometidas ou não por DA provável. Métodos: Para este propósito, uma amostra de mulheres residentes na comunidade do Distrito Federal (≥55 anos de idade, n=74) portadoras do alelo ApoE Ɛ4 foi avaliada clinicamente com base nos critérios da Associação Americana de Psiquiatria e da Escala de Avaliação da Doença de Alzheimer para diagnosticar ou descartar provável DA, escala de classificação de demência clínica utilizada para o estadiamento da demência. O RNA total foi isolado de amostras de sangue total obtidas do grupo controle (n = 38) e do grupo DA (n = 36). Um conjunto de 25 miRNAs maduros foi selecionado para avaliação baseado em evidências experimentais de interação com genes ligados à neuropatologia da DA de início tardio. Concentrações no sangue total foram determinadas por qRT-PCR. Resultados e Discussão: Quando pacientes com DA foram comparados com indivíduos não dementes, apenas a concentração de miR-9 diferiu entre grupos (P = 0,001), com redução mediana da ordem de 3 vezes dos níveis circulantes no grupo DA. Conclusão: Nossos achados sugerem que o miR-9 circulante pode ser um biomarcador sanguíneo potencial para a DA provável, corroborado por evidências da literatura sobre sua implicação na amiloidogênese.CAPESIntroduction: Recent evidence suggests that changes in circulating microRNA levels may be promising biomarkers for the clinical diagnosis of Alzheimer's disease (AD). We hypothesized that whole blood microRNAs (miRNAs) may be useful in identifying individuals with established AD. Objective: To compare levels of a selected group of circulating miRNAs from whole blood of women with or without probable AD. Methods: For this purpose, a sample of women from the Federal District community (≥55 years, n=74) carrying the ApoE Ɛ4 allele was clinically evaluated based on criteria from the American Psychiatric Association and the Alzheimer's Disease Rating Scale to diagnose or rule out. probable AD, clinical dementia rating scale used for staging dementia. Total RNA was isolated from whole blood samples obtained from the control group (n = 38) and the AD group (n = 36). A set of 25 mature microRNAs was selected for evaluation based on experimental evidence of interaction with genes linked to late-onset AD neuropathology. Whole blood concentrations were determined by qRT-PCR. Results and Discussion:When AD patients were compared with non-demented individuals, only the miR-9 concentration differed between groups (P = 0.001), with a median reduction of 3 times the circulating levels in the AD group. Conclusion: Our findings suggest that circulating miR-9 may be a potential blood biomarker for probable AD, corroborated by evidence in the literature about its implication in amyloidogenesis

The influence of intense intermitent versus moderate continuous exercise on postprandial lipemia

INTRODUCTION: Postprandial lipemia is characterized by an increased concentration of circulating lipids after fat intake and is an independent risk factor for cardiovascular disease. Exercise is known to reduce postprandial lipemia and its negative clinical outcomes. OBJECTIVE: This study investigated the effect of intense intermittent versus moderate continuous exercise using the same energy expenditure in postprandial lipemia. MATERIALS AND METHODS: Twenty healthy men (aged 21.5 + 3.5 years) performed a random sequence of either rest or 500 Kcal tests separated by a minimum 48 h interval as follows: (a) no exercise (control), (b) intense intermittent exercise, or (c) moderate continuous exercise. Each test series was completed 30 min before ingestion of a high-fat meal (1 g fat/kg). Venous blood was collected before and at 1, 2, 3 and 4 hours after the high-fat meal. Postprandial lipemia was assessed using the area under the curve approach as well as a kinetic profile of mean lipid variables. Statistical significance was tested at the p<0.05 level. RESULTS: With both statistical approaches, intense intermittent and moderate continuous exercises were both effective in reducing postprandial triglycerides; however, only intense intermittent exercise reduced the levels of postprandial very low density lipoprotein. Intense intermittent and continuous exercise produced lower levels of insulinemia using the area under the curve analysis only. CONCLUSION: Intense intermittent or continuous exercise with an energy expenditure of 500 kcal completed 30 min before ingestion of high-fat meal reduced postprandial lipid levels to different levels in physically active men. Understanding these relevant differences will enable clinicians to provide the best exercise prescription for patients

The influence of intense intermittent versus moderate continuous exercise on postprandial lipemia

INTRODUCTION: Postprandial lipemia is characterized by an increased concentration of circulating lipids after fat intake and is an independent risk factor for cardiovascular disease. Exercise is known to reduce postprandial lipemia and its negative clinical outcomes. OBJECTIVE: This study investigated the effect of intense intermittent versus moderate continuous exercise using the same energy expenditure in postprandial lipemia. MATERIALS AND METHODS: Twenty healthy men (aged 21.5 + 3.5 years) performed a random sequence of either rest or 500 Kcal tests separated by a minimum 48 h interval as follows: (a) no exercise (control), (b) intense intermittent exercise, or (c) moderate continuous exercise. Each test series was completed 30 min before ingestion of a high-fat meal (1 g fat/kg). Venous blood was collected before and at 1, 2, 3 and 4 hours after the high-fat meal. Postprandial lipemia was assessed using the area under the curve approach as well as a kinetic profile of mean lipid variables. Statistical significance was tested at the p<0.05 level. RESULTS: With both statistical approaches, intense intermittent and moderate continuous exercises were both effective in reducing postprandial triglycerides; however, only intense intermittent exercise reduced the levels of postprandial very low density lipoprotein. Intense intermittent and continuous exercise produced lower levels of insulinemia using the area under the curve analysis only. CONCLUSION: Intense intermittent or continuous exercise with an energy expenditure of 500 kcal completed 30 min before ingestion of high-fat meal reduced postprandial lipid levels to different levels in physically active men. Understanding these relevant differences will enable clinicians to provide the best exercise prescription for patients

Obesidade e capacidade funcional podem estar associadas com diversas comorbidades em idosos residentes em instituições de longa permanência

ResumoIntrodução: o envelhecimento é um processo complexo que geralmente ocorre concomitantemente com o declínio e a reformulação das diferentes funções do corpo, dentre as quais, destacam-se as mudanças antropométricas, funcionais e cognitivas, bem como o aparecimento de diversos problemas de saúde. Objetivo: analisar a correlação entre a obesidade e a capacidade funcional com o déficit cognitivo e outras comorbidades em idosos residentes em Instituições de Longa Permanência. Materiais e Métodos: estudo transversal descritivo realizado em 40 idosos de ambos os sexos residentes em Instituições de Longa Permanência. Foram mensurados dados antropométricos, cognitivos e funcionais. As comorbidades foram verificadas com base no prontuário médico. Os dados foram analisados por meio do teste T independente, Teste Qui-Quadrado e Correlação Linear de Pearson. Foi adotado o valor de p&lt;0,05 para apontar as diferenças significativas. O programa SPSS, 22.0 foi usado para realizar as análises. Resultado: o déficit cognitivo foi de 73% para mulheres e 48% para homens. A força de preensão palmar dominante foi de 11,6 ± 7,5 no sexo masculino e 6,2 ± 5,2 no sexo feminino, e não dominante 10,3 ± 6,5 e 5,3 ± 3,8 para masculino e feminino respectivamente. O IMC foi 25,9 ± 3,7 e 28,1 ± 5,0 para homens e mulheres respectivamente. Conclusão: a obesidade e o déficit cognitivo estão elevados entre os idosos institucionalizados. Houve associação do IMC e da força com as comorbidades, porém não com o desempenho cognitivo. Adicionalmente, os resultados dos testes funcionais se mostraram bastante comprometidos, uma vez que estão bastante inferiores aos valores encontrados em outros estudos. AbstractIntroduction: aging is a complex process that usually occurs concomitantly with the decline and the reformulation of the different body functions, among which, the anthropometric, functional and cognitive changes are distinguished, as well as the appearance of several health disorders. Objective: analyze the correlation between obesity and functional capacity with cognitive impairment and other comorbidities in the elderly living in long-stay institutions. Materials and Methods: descriptive cross-sectional study conducted in 40 elderly of both genders, who live in LSI. Anthropometric, cognitive and functional data were measured. Comorbidities were verified based in medical records. Data were analyzed using independent T test, chi-square test and Pearson’s linear correlation. It was adopted p value &lt;0.05 to point out the significant differences. Result: cognitive impairment was 73% for women and 48% for men. The strength of dominant handgrip was 11.6 ± 7.5 in males and 6.2 ± 5.2 in females, and non-dominant 10.3 ± 6.5 and 5.3 ± 3.8 for male and female respectively. BMI was 25.9 ± 3.7 and 28.1 ± 5.0 for men and women respectively. Conclusion: obesity and cognitive impairment are high among the institutionalized elderly. There was an association of BMI and strength with comorbidities, but not with cognitive performance. Additionally, the results of the functional tests showed much compromised, since they are well below than the values found in other studies. figshare DOI: 10.6084/m9.figshare.819860

Dissociação do polimorfismo do gene da enzima conversora de angiotensina com a força, volume e qualidade muscular em mulheres sedentárias

Introduction: Strength and muscle mass reflect the interactions between envi - ronmental factors and genetics. Objective: To analyze the influence of the geno - type of the angiotensin converting enzyme (ACE) on strength, muscle volume, quality and total-body skeletal muscle mass in middle-aged sedentary women. Methods: The sample consisted of 32 women divided into two groups according to the I/D polymorphism that underwent assessments of muscular strength tests of 1RM. In addition muscle volume measurements of the quadriceps and biceps by ultrasound were obtained, and the muscle quality of the biceps and quadri - ceps. Results: There was no difference on muscle strength, volume and quality neither of the quadriceps and biceps muscles, nor in the total-body skeletal mus - cle mass. Conclusions: The findings of this study did not demonstrate an impor - tant role of the polymorphism in the ACE gene in determining the phenotypes of strength, muscle volume and quality of middle-aged sedentary women

Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α.

Objective: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ]) in response to multivariate drug directions for blood pressure (BP) control. Methods: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention. Results: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P0.01) at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin–angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group. Conclusion: Our data demonstrates that a clinically guided antihypertensive treatment is effective in reversing the low-grade proinflammatory state of serum cytokines found in post¬menopausal women and support extracardiac benefits from diuretics and renin–angiotensin system antagonist

FTO gene variant and association with overweight in Brazilian male students

Obesity is considered a disease with multiple etiologies. Recent advances in technology have pointed candidate genes that are related to weight gain in several populations. However, in countries with ethnic miscegenation, such as Brazil, studies of this nature with students are still scarce. The aim of the present study was to compare anthropometric variables of Brazilian male students according to the genotypes of the rs9939609 of the FTO gene. In order to do so, 205 participants underwent body mass, height, waist circumference and skinfold thickness measurements. Body mass index (BMI), waist-to-height ratio and body fat percentage were calculated. Volunteers were characterized as overweight according to the BMI-for-age z-score. Participants were genotyped according to the single nucleotide polymorphism rs9939609 of the FTO gene (AA, AT and TT). ANOVA one-way with Bonferroni’s post hoc was performed to compare genotypes and anthropometric variables. Odds Ratio was calculated to reveal increased chances of presenting higher body mass index z-score, waist-to-height ratio and body fat percentage. Participants homozygous for the A allele presented significantly higher values of BMI-for-age z-score (0.38±1.01 vs. -0.29±1.15), waist circumference (77.15±6.51 vs. 72.85±7.36 cm) and waist-to-height ratio (0.44±0.04 vs. 0.42±0.04) when compared to individuals with the TT genotype. The A allele of the rs9939609 of the FTO gene seems to influence in the adiposity of male students

Serum Levels of Matrix Metalloproteinase-1 in Brazilian Patients with Benign Prostatic Hyperplasia or Prostate Cancer

Metalloproteinases (MMPs) are involved in metastatic tumor processes, with changes in circulating levels detected in several cancer types. Here, we compare serum concentrations of metalloproteinase-1 (MMP-1) across individuals clinically diagnosed with prostate cancer (PCa) or benign prostatic hyperplasia (BPH), correcting results for the rs495366 single nucleotide polymorphism (SNP) that predisposes to differential MMP-1 levels. 196 men aged ≥50 years were followed at a university hospital urology outpatient clinic, with clinical, anthropometric, and rectal examinations performed by one urologist. Blood samples obtained prior to any clinical intervention provided baseline MMP-1 and total/free PSA levels as well as metabolic, hormonal, and inflammatory markers. The SNP was genotyped by real-time PCR. Participants with medical and/or laboratory profile compatible with malignancy composed the PCa group when confirmed by the Gleason scale. As expected, A-allele homozygotes showed reduced levels of MMP-1. Genotype-adjusted analyses revealed the mean MMP-1 level as 2-fold higher in PCa carriers compared to BPH patients. No other differences were found according to the prostatic condition or genotypic distribution, except for the expected raise in total and free PSA levels in PCa. In conclusion, increased serum levels of MMP-1 were observed in this context of prostatic malignancy compared to a benign phenotype, regardless of a genetic influence

Multiple Cold-Water Immersions Attenuate Muscle Damage but not Alter Systemic Inflammation and Muscle Function Recovery: A Parallel Randomized Controlled Trial

International audienceThe aim of this study was to investigate the effects of multiple cold-water immersions (CWIs) on muscle function, markers of muscle damage, systemic inflammation and ECM degradation following exercise-induced muscle damage (EIMD). Thirty physically active males were randomly assigned to either a control (n = 15) or cold-water immersion (CWI) group (n = 15). The CWI group performed one immersion (10 degrees C for 20 min) at post-exercise and every 24 h for the following 72 h, while the control group remained in a seated position during these corresponding periods. Muscle strength, vertical jump height, muscle thickness, delayed-onset muscle soreness (DOMS), systemic creatine kinase (CK), C-reactive protein (CRP), inflammatory cytokines and matrix metalloproteinase-2 (MMP-2) activity were assessed at Pre, Post, 24, 48, 72, 96 and 168 h following EIMD. No significant time x group interaction was obtained for muscle strength, vertical jump height recovery and MMP-2 activity (p > 0.05). At 24 h, muscle thickness from the CWI group returned to baseline and was lower than the control (p = 0.04). DOMS returned to baseline at 168 h for the CWI group (p = 0.109) but not for the control (p = 0.008). At 168 h, CK showed a time-group difference with a greater peak for the control group (p = 0.016). In conclusion, multiple CWIs attenuated muscle damage, but not altered systemic inflammation and muscle function recovery