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1.
Cardiovasc Res ; 118(8): 2006-2017, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34173822

RESUMO

AIMS: Extracellular chromatin and deoxyribonuclease (DNase) have been identified as important players of thrombosis, inflammation, and homeostasis in a murine model. We previously demonstrated that activated neutrophils release neutrophil extracellular traps (NETs) at the culprit site in ST-elevation myocardial infarction (STEMI), which significantly contribute to extracellular chromatin burden, and are associated with larger infarcts. To understand the correlation between neutrophil activation, extracellular chromatin, and infarct size (IS), we investigated these parameters in a porcine myocardial infarction model, and at different time points and sites in a prospective STEMI trial with cardiac magnetic resonance (CMR) endpoints. METHODS AND RESULTS: In a prospective STEMI trial (NCT01777750), 101 STEMI patients were included and blood samples were obtained from first medical contact until 6 months after primary percutaneous coronary intervention (pPCI) including direct sampling from the culprit site. CMR was performed 4 ± 2 days and 6 months after pPCI. Neutrophil counts, markers of extracellular chromatin, and inflammation were measured. Double-stranded deoxyribonucleic acid (dsDNA), citrullinated histone 3, nucleosomes, myeloperoxidase, neutrophil elastase, and interleukin (IL)-6 were significantly increased, while DNase activity was significantly decreased at the culprit site in STEMI patients. High neutrophil counts and dsDNA levels at the culprit site correlated with high microvascular obstruction (MVO) and low ejection fraction (EF). High DNase activity at the culprit site correlated with low MVO and high EF. In correspondence, dsDNA correlated with IS in the porcine myocardial infarction model. In porcine infarcts, neutrophils and extracellular chromatin were detected in congested small arteries corresponding with MVO. Markers of neutrophil activation, extracellular chromatin, DNase activity and CMR measurements correlated with markers of systemic inflammation C-reactive protein and IL-6 in patients. CONCLUSIONS: NETs and extracellular chromatin are important determinants of MVO in STEMI. Rapid degradation of extracellular chromatin by DNases appears to be crucial for microvascular patency and outcome.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Adulto , Idoso , Biomarcadores , Cromatina , DNA , Desoxirribonucleases , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia
2.
Wien Klin Wochenschr ; 134(1-2): 1-6, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34223999

RESUMO

BACKGROUND: Testosterone plays an important role in the regulation of glucose metabolism. While earlier studies have shown that it has a protective effect in males, unfavorable effects of testosterone on glucose metabolism have been reported in females; however, whether there is a sex-specific relationship between testosterone and glucose metabolism in patients with prediabetes has not been investigated in detail hitherto. METHODS: This cross-sectional analysis investigated 423 males and 287 females with diagnosed prediabetes. Detailed assessment of their metabolic profiles was performed, including a 2­h oral glucose tolerance test (OGTT), HbA1c levels, calculation of insulin resistance with homeostatic model assessment for insulin resistance (HOMA-IR), assessment of lipid metabolism, anthropometric parameters and the fatty liver index (FLI). By using Spearman's correlation test, we investigated the sex-specific relationship between testosterone and metabolism in the prediabetic individuals. RESULTS: In the present study, prediabetic females (mean age 58.6 years, confidence interval [CI: 57.6 y; 59.5 y]) were characterized by lower fasting plasma glucose levels (104.2 mg/dl [CI: 103.0 mg/dl; 105.4 mg/dl] vs. 106.9 mg/dl [CI: 106.0 mg/dl; 107.8 mg/dl]) and a lower FLI (49.5 [CI: 45.7; 53.2] vs. 58.8 [CI: 55.8; 61.8]), but presented with a higher risk of developing manifest type 2 diabetes in the next 10 years (FINDRISK score: 17.6 [CI: 17.1; 18.1] vs. 16.1 [CI: 15.7; 16.5]) when compared to prediabetic males (mean age: 58.04 years [CI: 57.0 y; 59.1 y]). Testosterone was negatively related to insulin resistance (HOMA-IR: Spearman's ρ: -0.33, p < 0.01), 2­h stimulated glucose levels during the OGTT (ρ = -0.18, p < 0.01), HbA1c levels (ρ = -0.13, p < 0.05), FLI and BMI in prediabetic males; however, no relationship between testosterone and metabolic parameters could be found in prediabetic females. CONCLUSION: The increase of testosterone levels in males was related to a more favorable glucose metabolism, including lower HbA1c, lower stimulated glucose levels and higher insulin sensitivity; however, in prediabetic females, testosterone was not related to glucose metabolism.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Estado Pré-Diabético , Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/diagnóstico , Testosterona
3.
Int J Endocrinol ; 2021: 2811756, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707658

RESUMO

INTRODUCTION: We aim to investigate the effect of vitamin D on metabolic parameters in a population with prediabetes and to detect possible sex differences. METHODS: In 621 patients with diagnosed prediabetes, glucose, lipid, and anthropometric parameters were measured. Furthermore, the interaction of 25-OH-vitamin D (25-hydroxyvitamin D) with metabolic and glucose metabolism parameters was analysed in the total prediabetic population, as well as after stratification by sex (female vs. male prediabetic subgroup), by logistic regression. RESULTS: 25-OH-vitamin D was negatively related to cholesterol, BMI, fatty liver index, insulin, and HOMA-IR. Especially in the male prediabetic cohort, 25-OH-vitamin D levels negatively correlated with total cholesterol levels (r = -0.17, p=0.001), with triglycerides (r = -0.17, p=0.001), and with HbA1c levels (r = -0.14, p=0.010). Only in the female cohort with prediabetes, we found a negative correlation of 25-OH-vitamin D levels with systolic (r = -0.18, p=0.005) and diastolic blood pressures (r = -0.23, p < 0.001). CONCLUSION: In this study, in females with prediabetes, 25-OH-vitamin D was notably related to a more favourable metabolic profile, including lower total cholesterol and higher HDL cholesterol levels. On the contrary, in men with prediabetes, there was a stronger association between 25-OH-vitamin D and cholesterol-HDL quotient, as well as fatty liver index was observed in the male prediabetic subgroup. Therefore, sex differences should be considered in future studies on vitamin D and glucose tolerance status.

4.
Basic Res Cardiol ; 116(1): 29, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33891165

RESUMO

Upon activation, neutrophils release neutrophil extracellular traps (NETs), which contribute to circulating DNA burden and thrombosis, including ST-segment elevation myocardial infarction (STEMI). Deoxyribonuclease (DNase) 1 degrades circulating DNA and NETs. Lower DNase activity correlates with NET burden and infarct size. The DNase 1 Q222R single nucleotide polymorphism (SNP), impairing DNase 1 function, is linked with myocardial infarction. We assessed whether the Q222R SNP is connected to increased NET burden in STEMI and influences long-term outcomes. We enrolled 711 STEMI patients undergoing primary percutaneous coronary intervention (pPCI), and 1422 controls. Genotyping was performed for DNase 1 Q222R SNP. DNase activity, double-stranded (ds)DNA and citrullinated histone H3 were determined in culprit site and peripheral plasma during pPCI. The association of the Q222R variant on cardiovascular and all-cause mortality was assessed by multivariable Cox regression adjusted for cardiovascular risk factors. Homozygous Q222R DNase 1 variant was present in 64 (9.0%) STEMI patients, at the same frequency as in controls. Patients homozygous for Q222R displayed less DNase activity and increased circulating DNA burden. In overall patients, median survival was 60 months. Homozygous Q222R variant was independently associated with cardiovascular and all-cause mortality after STEMI. dsDNA/DNase ratio independently predicted cardiovascular and all-cause mortality. These findings highlight that the Q222R DNase 1 SNP is associated with increased NET burden and decreased compensatory DNase activity, and may serve as an independent risk factor for poor outcome after STEMI.


Assuntos
Desoxirribonuclease I/genética , Armadilhas Extracelulares/metabolismo , Polimorfismo de Nucleotídeo Único , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Idoso , Áustria , Estudos de Casos e Controles , Desoxirribonuclease I/metabolismo , Feminino , Estudos de Associação Genética , Alemanha , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Prognóstico , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fatores de Tempo
5.
Psychophysiology ; 58(5): e13799, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655551

RESUMO

In an aging society, late-life depression has become an increasing problem. There is evidence that physical activity ameliorates depressive symptoms and increases the quality of life (QoL). However, the underlying mechanisms are still poorly understood. Myokines are molecules secreted in response to muscle contraction. Some of them can cross the blood-brain barrier, making them promising candidates for mediating the beneficial effects of physical activity on mood. The present study aims to compare circulating myokine levels to depression/QoL in older athletes and controls. 55 athletes, 57 controls >59 years were enrolled. The assessment included ergometry, magnetic resonance imaging, blood withdrawal, and neuropsychological testing. Serum interleukin-6 (IL-6), irisin, brain-derived neurotrophic factor (BDNF), kynurenine, and cathepsin B were analyzed and compared to surrogates of depression and quality of life. Athletes presented with higher levels of Cathepsin B. Among controls, all myokines but irisin were associated with age. Also, among controls, kynurenine and IL-6 correlated inversely with specific dimensions of quality of life questionnaires, and IL-6 further with depressive symptoms and decreased physical performance. No such associations could be found among athletes. Irisin levels were inversely associated with mild depression and low-grade white matter-lesions in the brain and predicted impaired QoL. The circulating levels of several myokines/muscle activity-related factors appear to be associated with depressive symptoms and impaired QoL among older adults. However, in athletes, some of these connections seem ameliorated, suggesting additional stressors (as f.e. age) or a different pathomechanism among athletes.


Assuntos
Atletas , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Catepsina B/metabolismo , Depressão/metabolismo , Fibronectinas/metabolismo , Interleucina-6/metabolismo , Cinurenina/metabolismo , Qualidade de Vida , Fatores Etários , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Corrida de Maratona , Pessoa de Meia-Idade , Desempenho Físico Funcional , Estudos Retrospectivos
6.
Blood ; 137(8): 1104-1116, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33512471

RESUMO

Acute pulmonary embolism generally resolves within 6 months. However, if the thrombus is infected, venous thrombi transform into fibrotic vascular obstructions leading to chronic deep vein thrombosis and/or chronic thromboembolic pulmonary hypertension (CTEPH), but precise mechanisms remain unclear. Neutrophils are crucial in sequestering pathogens; therefore, we investigated the role of neutrophil extracellular traps (NETs) in chronic thrombosis. Because chronic pulmonary thrombotic obstructions are biologically identical to chronic deep venous thrombi, the murine inferior vena cava ligation model was used to study the transformation of acute to chronic thrombus. Mice with staphylococcal infection presented with larger thrombi containing more neutrophils and NETs but less resolution. Targeting NETs with DNase1 diminished fibrosis and promoted thrombus resolution. For translational studies in humans, we focused on patients with CTEPH, a severe type of deep venous and pulmonary artery fibrotic obstruction after thrombosis. Neutrophils, markers of neutrophil activation, and NET formation were increased in CTEPH patients. NETs promoted the differentiation of monocytes to activated fibroblasts with the same cellular phenotype as fibroblasts from CTEPH vascular occlusions. RNA sequencing of fibroblasts isolated from thrombo-endarterectomy specimens and pulmonary artery biopsies revealed transforming growth factor-ß (TGF-ß) as the central regulator, a phenotype which was replicated in mice with fibroblast-specific TGF-ß overactivity. Our findings uncover a role of neutrophil-mediated inflammation to enhance TGF-ß signaling, which leads to fibrotic thrombus remodeling. Targeting thrombus NETs with DNases may serve as a new therapeutic concept to treat thrombosis and prevent its sequelae.


Assuntos
Armadilhas Extracelulares , Hipertensão Pulmonar/patologia , Neutrófilos/patologia , Embolia Pulmonar/patologia , Trombose/patologia , Animais , Células Cultivadas , Doença Crônica , Feminino , Fibrose , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade
7.
Sci Total Environ ; 668: 678-684, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-30856576

RESUMO

OBJECTIVE: The neurotoxicity of lead is well-known and even low exposure levels potentially impact neurocognitive abilities. This metaanalysis aimed to investigate associations between neurocognitive performance and lead exposure in adults and further assess potential effect thresholds. MATERIAL AND METHODS: Articles indexed in Medline published until January 2017 reporting associations between lead exposure, blood lead, cognitive abilities and sensomotoric performance were included. The unbiased, standardized mean differences g between lead exposure and control groups extracted from the primary studies were pooled using a three-level, random-effects meta-analytic model with a restricted maximum likelihood estimator. Moderator analyses were conducted using weighted, mixedeffects regression analyses. RESULTS: We identified 22 articles (n=3,849 participants, mean age 39.94±7.87years) published between 1976 and 2014 reporting lead exposure effects on cognitive and sensomotoric parameters (verbal abilities, visuospatial abilities, memory, attention, psychomotor function). On average, blood lead concentrations were 21.09±6.44 µg/dl higher in exposed than in control subjects. After exclusion of outliers, the random-effects three-level meta-analysis identified a significant (p<.001) pooled mean difference between exposure and control groups. Except for a smaller effect in the digit symbol test (p<.05), lead exposure did not result in different outcomes across the examined cognitive measures. Based on a marginally significant (p=.06) effect of difference in exposure levels, a blood lead increase of 10 µg/dl translated into a decline in cognitive abilities of Hedges g=.09. CONCLUSIONS: Neurocognitive performance in adults with occupational or environmental lead exposure was significant impaired with regard to the examined parameters. However, further studies are needed for the determination of effect thresholds and reversibility.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/sangue , Chumbo/sangue , Adulto , Cognição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor
8.
Sci Rep ; 8(1): 9151, 2018 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-29904183

RESUMO

Burnout and work-related stress symptoms of anxiety disorder and depression cause prolonged work absenteeism and early retirement. Hence, reliable identification of patients under risk and monitoring of treatment success is highly warranted. We aimed to evaluate stress-specific biomarkers in a population-based, "real-world" cohort (burnouts: n = 40, healthy controls: n = 26), recruited at a preventive care ward, at baseline and after a four-month follow up, during which patients received medical and psychological treatment. At baseline, significantly higher levels of salivary cortisol were observed in the burnout group compared to the control group. This was even more pronounced in midday- (p < 0.001) and nadir samples (p < 0.001) than for total morning cortisol secretion (p < 0.01). The treatment program resulted in a significant reduction of stress, anxiety, and depression scores (all p < 0.001), with 60% of patients showing a clinically relevant improvement. This was accompanied by a ~30% drop in midday cortisol levels (p < 0.001), as well as a ~25% decrease in cortisol nadir (p < 0.05), although not directly correlating with score declines. Our data emphasize the potential usefulness of midday and nadir salivary cortisol as markers in the assessment and biomonitoring of burnout.


Assuntos
Esgotamento Psicológico/metabolismo , Ritmo Circadiano , Hidrocortisona/metabolismo , Saliva/metabolismo , Vigília , Adulto , Biomarcadores/metabolismo , Esgotamento Psicológico/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
PLoS One ; 12(5): e0177174, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28475643

RESUMO

Endurance sports are enjoying greater popularity, particularly among new target groups such as the elderly. Predictors of future physical capacities providing a basis for training adaptations are in high demand. We therefore aimed to estimate the future physical performance of elderly marathoners (runners/bicyclists) using a set of easily accessible standard laboratory parameters. To this end, 47 elderly marathon athletes underwent physical examinations including bicycle ergometry and a blood draw at baseline and after a three-year follow-up period. In order to compile a statistical model containing baseline laboratory results allowing prediction of follow-up ergometry performance, the cohort was subgrouped into a model training (n = 25) and a test sample (n = 22). The model containing significant predictors in univariate analysis (alanine aminotransferase, urea, folic acid, myeloperoxidase and total cholesterol) presented with high statistical significance and excellent goodness of fit (R2 = 0.789, ROC-AUC = 0.951±0.050) in the model training sample and was validated in the test sample (ROC-AUC = 0.786±0.098). Our results suggest that standard laboratory parameters could be particularly useful for predicting future physical capacity in elderly marathoners. It hence merits further research whether these conclusions can be translated to other disciplines or age groups.


Assuntos
Alanina Transaminase/sangue , Atletas , Colesterol/sangue , Ácido Fólico/sangue , Peroxidase/sangue , Aptidão Física/fisiologia , Ureia/sangue , Idoso , Ciclismo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resistência Física/fisiologia , Estudos Prospectivos , Corrida/fisiologia
10.
Eur J Clin Invest ; 47(3): 231-240, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28102901

RESUMO

BACKGROUND: Risk of arrhythmic death is considered highest in ischemic heart disease with severe left ventricular ejection fraction (LVEF) reduction. Non-invasive testing should improve decision-making of prophylactic defibrillator (ICD) implantation. DESIGN: We enrolled 120 patients with ischemic heart disease and LVEF < 50% and 30 control subjects without ischemic heart disease and normal LVEF. An initial assessment, a second assessment after 3 years and a final follow-up comprised of pharmacological baroreflex testing (BRS), short-term spectral [low-frequency (LF) to high-frequency (HF) ratio] and long-term time-domain analysis of heart rate variability (SDNN), exercise Microvolt T-wave alternans (MTWA) and others. RESULTS: The median follow-up was 7·5 years. Resuscitated cardiac arrest and arrhythmic death due to ventricular arrhythmias ≥ 240/min was observed in 18% and 15% of patients, respectively. Cardiac death was observed in 28% of patients. The incidence of arrhythmic death and resuscitated cardiac arrest was identical in patients with ischemic heart disease with LVEF < 30% and ≥ 30%. No significant difference between subgroups with LVEF of < 30%, 30-39% and ≥ 40% was found either. MTWA, BRS, SDNN and LF to HF ratio failed to identify patients at risk of arrhythmic death in a multiple regression model. CONCLUSIONS: Ischemic heart disease patients with LVEF < 30% and ≥ 30% face the same risk of arrhythmic death. Stratification techniques fail to identify high-risk patients. Therefore, the current practice to constrain prophylactic ICDs to patients with severely reduced LVEF seems to be insufficient.


Assuntos
Arritmias Cardíacas/etiologia , Morte Súbita Cardíaca/etiologia , Isquemia Miocárdica/complicações , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Idoso , Arritmias Cardíacas/mortalidade , Estudos de Casos e Controles , Feminino , Seguimentos , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Estudos Prospectivos , Medição de Risco , Método Simples-Cego , Fatores de Tempo
11.
PLoS One ; 11(6): e0157695, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27304888

RESUMO

BACKGROUND AND AIM: Recent studies revealed a link between hypovitaminosis D3 and the risk for hyperglycemia. Further mechanistic and interventional investigations suggested a common reason for both conditions rather than a causal relationship. Exposure to sunlight is the most relevant source of vitamin D3 (25(OH)D), whereas adipose tissue is able to store relevant amounts of the lipophilic vitamin. Since running/bicycling leads to increased out-door time and alters physiological response mechanisms, it can be hypothesized that the correlation between hypovitaminosis D3 and hyperglycemia might be disturbed in outdoor athletes. METHODS: 47 elderly marathoners/bicyclists and 47 age/sex matched controls were studied in a longitudinal setting at baseline and after three years. HbA1c as a surrogate for (pre-)diabetic states was quantified via HPLC, 25(OH)D levels were measured by means of chemiluminescent assays. Physical performance was assessed by ergometry. RESULTS: When adjusted for seasonal variations, 25(OH)D was significantly higher in athletes than in controls. 25(OH)D levels inversely correlated with triglycerides in both groups, whereas only in controls an association between high BMI or low physical performance with hypovitaminosis D3 had been found. Likewise, the presence of hypovitaminosis D3 at baseline successfully predicted hyperglycemia at the follow up examinations within the control group (AUC = 0.85, 95% CI [0.74, 0.96], p < .001, statistically independent from BMI), but not in athletes. CONCLUSION: Our data suggest that mechanisms of HbA1c elevation might differ between athletes and controls. Thus, intense physical activity must be taken into account as a potential pre-analytic confounder when it is aimed to predict metabolic risk by vitamin D3 levels.


Assuntos
Atletas , Colecalciferol/metabolismo , Hiperglicemia/metabolismo , Deficiência de Vitamina D/metabolismo , Idoso , Ciclismo/fisiologia , Índice de Massa Corporal , Ergometria , Exercício Físico/fisiologia , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Corrida/fisiologia , Estações do Ano , Fatores de Tempo , Deficiência de Vitamina D/fisiopatologia
12.
Sci Total Environ ; 544: 24-30, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26657246

RESUMO

It is unclear whether electromagnetic fields emitted by mobile phone base stations affect well-being in adults. The existing studies on this topic are highly inconsistent. In the current paper we attempt to clarify this question by carrying out a meta-analysis which is based on the results of 17 studies. Double-blind studies found no effects on human well-being. By contrast, field or unblinded studies clearly showed that there were indeed effects. This provides evidence that at least some effects are based on a nocebo effect. Whether there is an influence of electromagnetic fields emitted by mobile phone base stations thus depends on a person's knowledge about the presence of the presumed cause. Taken together, the results of the meta-analysis show that the effects of mobile phone base stations seem to be rather unlikely. However, nocebo effects occur.


Assuntos
Telefone Celular/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Adulto , Método Duplo-Cego , Campos Eletromagnéticos , Humanos , Ondas de Rádio
13.
Neuropsychobiology ; 71(3): 168-75, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25998702

RESUMO

BACKGROUND/AIMS: Depression is a highly prevalent disorder in elderly individuals. A genetic variant (rs6265) of the brain-derived neurotrophic factor (BDNF) impacting on emotion processing is known to increase the risk for depression. We aim to investigate whether intensive endurance sports might attenuate this genetic susceptibility in a cohort of elderly marathon athletes. METHODS: Fifty-five athletes and 58 controls were included. rs6265 of the BDNF gene was genotyped by the TaqMan method. Depressive symptoms were assessed by standardized self-rating tests (BDI = Beck Depression Inventory, GDS = Geriatric Depression Scale). RESULTS: In multivariable analysis of BDI and GDS scores, the interaction between group (athletes vs. controls) and genotypes ([C];[C] vs. [C];[T] + [T];[T]) was found to be statistically significant (BDI: p = 0.027, GDS: p = 0.013). Among [C];[C] carriers, merely controls had an increased relative risk of 3.537 (95% CI = 1.276-9.802) of achieving a subclinical depression score ≥10 on the BDI. There was no such effect in carriers of the [T] allele. In a multivariable binary logistic regression, genetic information, group (athletes/controls), but no information on rs6265 allele carrier status presented as a significant predictor of BDI scores ≥10. CONCLUSION: Physical exercise positively affects BDNF effects on mood. Since 66Met BDNF secretion is impaired, this effect seems to be much stronger in [C];[C] homozygous individuals expressing the 66Val variant. This confirms that genetic susceptibility to depressive symptoms can indeed be influenced by endurance sports in elderly people.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Depressão/genética , Depressão/prevenção & controle , Exercício Físico , Predisposição Genética para Doença/genética , Predisposição Genética para Doença/prevenção & controle , Idoso , Atletas , Fator Neurotrófico Derivado do Encéfalo/sangue , Estudos de Casos e Controles , Estudos de Coortes , Depressão/sangue , Depressão/psicologia , Feminino , Predisposição Genética para Doença/psicologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Testes Psicológicos , Estatísticas não Paramétricas , Inquéritos e Questionários
14.
J Sport Exerc Psychol ; 37(6): 637-45, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26866771

RESUMO

A single nucleotide variant within the promoter of the 5-hydroxytryptamine1A (5HT1A) receptor, rs6295, is part of a binding site for the transcription factor. We aimed to ascertain whether the rs6295 mediates the effect of exercise on depressive mood in elderly endurance athletes. We prospectively enrolled 55 elderly athletes (marathon runners/bicyclists) and 58 controls. In a controlled, univariate model, an interaction between the [C]-allele and physical activity indicated that only among athletes, the variant resulting in an imperfect NUDR binding site was associated with a lower depression score. Hence, athletes presented with a significantly lower relative risk of achieving a suspicious depression score among carriers of at least one [C]-allele. Our results suggest that the positive effect of physical exercise on depressive mood might be mediated by the 5HT1A receptor and the extent of this protective effect seems to be enhanced by the [C]-allele of the rs6295 variant.


Assuntos
Atletas/psicologia , Depressão/genética , Resistência Física/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor 5-HT1A de Serotonina/genética , Idoso , Alelos , Proteínas de Ligação a DNA , Feminino , Humanos , Masculino , Proteínas Nucleares/metabolismo , Escalas de Graduação Psiquiátrica , Receptor 5-HT1A de Serotonina/metabolismo , Corrida/psicologia , Fatores de Transcrição
15.
Circ Arrhythm Electrophysiol ; 7(6): 1101-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25262115

RESUMO

BACKGROUND: Prophylactic defibrillator implantation is recommended in dilated, nonischemic heart disease and left ventricular ejection fraction of ≤0.30 to 0.35. Noninvasive testing should improve accuracy in decision making of prophylactic defibrillator implantation. METHODS AND RESULTS: We enrolled 60 patients (median age, 57 years) with dilated cardiomyopathy and left ventricular ejection fraction ≤0.50, and 30 control subjects (median age, 59 years) with left ventricular ejection fraction >0.50. The protocol included an initial assessment, a second assessment after 3 years, and a final follow-up: pharmacological baroreflex testing (baroreceptor reflex sensitivity), short-term spectral analysis of heart rate variability (low frequency/high frequency), and long-term time domain analysis (SD of all normal-to-normal R-R intervals), exercise microvolt T wave alternans, and signal-averaged ECG, and corrected QT-time. The median follow-up was 7 years. End points were cardiac death, resuscitated cardiac arrest, and arrhythmic death. Cardiac death was observed in 21 patients. Resuscitated cardiac arrest and arrhythmic death caused by ventricular tachyarrhythmias ≥240 per minute was observed in 7 and 10 patients, respectively. In the single time point analysis, microvolt T wave alternans, baroreceptor reflex sensitivity, and SD of all normal-to-normal R-R intervals at initial testing added significant information regarding cardiac death. Microvolt T wave alternans added information on resuscitated cardiac arrest or arrhythmic death at multiple time points (P<0.001). False-negative microvolt T wave alternans results were seen in 8% of patients. CONCLUSIONS: Noninvasive testing and left ventricular ejection fraction could not reliably identify patients with dilated cardiomyopathy at risk of fatal ventricular tachyarrhythmias. Therefore, the strategy to confine prophylactic implantable cardioverter-defibrillator implantation to patients with dilated cardiomyopathy and severely reduced LV function should be reconsidered.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Barorreflexo , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/mortalidade , Morte Súbita Cardíaca/etiologia , Técnicas de Apoio para a Decisão , Volume Sistólico , Função Ventricular Esquerda , Idoso , Pressão Sanguínea , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Estudos de Casos e Controles , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Eletrocardiografia , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Prevenção Primária/instrumentação , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
16.
Brain Behav Immun ; 37: 23-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24513877

RESUMO

A number of studies have shown that mental challenge under controlled experimental conditions is associated with elevations in inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). However, relatively little work has been done on the effects of 'naturalistic' stressors on acute changes in inflammatory markers. The present study examined whether perceived arousal, valence and dominance in musicians are associated with pro-inflammatory and oxidative responses to a concert situation. Blood and salivary samples obtained from 48 members of a symphony orchestra on the day of rehearsal (i.e., control situation) and on the following day of premiere concert (i.e., test situation) were used to determine changes in salivary cortisol, pro-inflammatory markers (plasma myeloperoxidase, serum CRP, plasma IL-6), oxidative stress markers (paraoxonase1 activity and malondialdehyde), and homocysteine, a risk factor for vascular disease. Results of regression analyses showed a significant trend to increased myeloperoxidase (MPO) response in individuals with low valence score. Both affective states, valence and arousal, were identified as significant predictors of cortisol response during concert. In addition, control levels of plasma malondialdehyde were positively correlated with differences in IL-6 levels between premiere and rehearsal (r=.38, p=.012), pointing to higher oxidative stress in individuals with pronounced IL-6 response. Our results indicate that stress of public performance leads to increased concentrations of plasma MPO (20%), IL-6 (27%) and salivary cortisol (44%) in musicians. The decreasing effect of pleasantness on the MPO response was highly pronounced in non-smokers (r=-.60, p<.001), suggesting a significant role of emotional valence in stress-induced secretion of MPO. Additional studies are needed to assess the generalizability of these findings to other 'naturalistic' stress situations.


Assuntos
Afeto/fisiologia , Estresse Psicológico/metabolismo , Adulto , Proteína C-Reativa/análise , Feminino , Humanos , Hidrocortisona/análise , Inflamação/metabolismo , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Música , Estresse Oxidativo/fisiologia , Peroxidase/sangue , Adulto Jovem
17.
Sci Total Environ ; 424: 11-5, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22421088

RESUMO

The potential effects of radiofrequency electromagnetic fields (RF-EMF) emitted by GSM mobile phones on subjective symptoms, well-being and physiological parameters have been investigated in many studies. However, the results have been ambiguous. The current meta-analysis aims to clarify whether RF-EMF have an influence on well-being in self-reported sensitive persons, as well as in non-sensitive people. A literature search revealed 17 studies including 1174 participants. The single effects for various subjective and objective outcomes were meta-analytically combined to yield a single population parameter. Dependant variables were subjective (e.g. headaches) and objective parameters (e.g. heart rate variability) of well-being. The results show no significant impact of short-term RF-EMF exposure on any parameter. Future research should focus on the possible effects of long-term exposure.


Assuntos
Telefone Celular , Campos Eletromagnéticos/efeitos adversos , Ondas de Rádio/efeitos adversos , Adulto , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Autorrelato , Fatores de Tempo , Adulto Jovem
18.
Bioelectromagnetics ; 33(2): 159-65, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21853449

RESUMO

During recent years, a large number of studies on the effects of electromagnetic fields emitted by cellular mobile phones on human cognitive performance have been carried out. However, the results have been ambiguous. We carried out the current meta-analysis in order to investigate the impact of electromagnetic fields emitted by mobile phones on human cognition. Seventeen studies were included in the meta-analysis as they fulfill several requirements such as single- or double-blind experimental study design, and documentation of means and standard deviations of dependent variables. The meta-analysis was carried out as a group comparison between exposed and non-exposed subjects. No significant effects of electromagnetic fields emitted by Global System for Mobile Communications (GSM) and Universal Mobile Telecommunications System (UMTS) mobile phones were found. Cognitive abilities seem to be neither impaired nor facilitated. Results of the meta-analysis suggest that a substantial short-term impact of high frequency electromagnetic fields emitted by mobile phones on cognitive performance can essentially be ruled out.


Assuntos
Telefone Celular , Cognição/fisiologia , Cognição/efeitos da radiação , Exposição Ambiental , Relação Dose-Resposta à Radiação , Medicina Baseada em Evidências , Humanos , Doses de Radiação
19.
J Occup Environ Med ; 53(3): 313-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21346629

RESUMO

OBJECTIVE: To evaluate the association between socioeconomic factors and suicide rates. METHODS: Analysis of time series of suicide rates, gross domestic product, unemployment rates, labor force participation, and divorce rates of 18 countries are analyzed by the application of panel-vector error correction models. Main outcome measures are the association between the socioeconomic factors and suicide rates. RESULTS: Decreasing economic growth and increasing divorce rates are significantly associated with increasing suicide rates in men. For women, increasing economic growth, increasing unemployment, and increasing divorce rates are significantly associated with increasing suicides. Increasing female labor force participation is associated with decreasing suicides. CONCLUSION: Socioeconomic factors are associated with suicide rates. However, this relationship differs by sex. The current results provide a strong argument that suicide prevention strategies must include the monitoring of socioeconomic development.


Assuntos
Países Desenvolvidos/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Estudos Transversais , Divórcio/estatística & dados numéricos , Desenvolvimento Econômico/estatística & dados numéricos , Emprego/estatística & dados numéricos , Feminino , Humanos , Masculino , Modelos Estatísticos , Análise de Regressão , Distribuição por Sexo , Fatores Socioeconômicos , Suicídio/economia , Desemprego/estatística & dados numéricos
20.
Wien Klin Wochenschr ; 122(23-24): 704-16, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21072603

RESUMO

BACKGROUND: Cognitive impairment of the elderly contributes to morbidity, loss of quality of life, and impairment of work ability in aging western societies. Thus strategies to maintain cognitive function at an advanced age imply a great challenge to Occupational Medicine. AIM: To study whether intensive endurance exercise training is associated with better cognitive performance and increases brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF). METHODS: Active elderly marathon runners or bicyclists older than 60 years were recruited and matched with an inactive control group according to age, sex, and education years. After exclusion of various diseases according to the study protocol 56 athletes and 58 controls could be selected for follow-up studies. The influence of endurance training on cognitive function was assessed by the use of the Vienna Neuropsychological Test Battery and the CERAD test battery. Other relevant outcomes were the levels of BDNF, IGF-1, Apo e4 carrier state, and self-ratings. RESULTS: The elderly marathon group performed better only in one specific cognitive task (the Five Point Test, p = 0.04) and almost significantly better in one additional test (the NAI Stroop Test, p = 0.08). Neither BDNF nor IGF-1 was related to the duration of daily exercise and no differences in the basal levels of these humoral growth factors in the exercise and the control cohort were found. Interestingly, we also found significantly decreased BDNF levels in subjects with Alzheimer's disease in the family in spite of the maintained normal cognitive performance (p = 0.01). CONCLUSION: These results suggest that extensive endurance exercise training might be beneficial for maintaining cognitive function in elderly persons. Our data demonstrate that beneficial endurance training effects are not linked to the upregulation of the examined neurotrophins. Since we found reduced BDNF-levels in subjects with a positive family history of Alzheimer's disease, we speculate that BDNF-reduction might precede cognitive impairment.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Transtornos Cognitivos/prevenção & controle , Transtornos Cognitivos/fisiopatologia , Cognição , Terapia por Exercício/métodos , Corrida , Somatomedinas/metabolismo , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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