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1.
Medicine (Baltimore) ; 98(37): e17179, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517874

RESUMO

We investigated oxidative stress parameters in the sera of patients with lung cancer and healthy individuals to evaluate their correlations with lung cancer.Ninety-four lung cancer patients and 64 healthy controls were enrolled after obtaining informed consent. Their sera oxidative stress parameters were measured.Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were significantly different between patients and healthy groups (all P < .001). TAS gradually decreased and TOS and OSI gradually increased from stage I to III, but it did not reach statistical significance (all P > .05). TAS and OSI were significantly different between the nonsmoking and smoking groups, radiotherapy and without radiotherapy groups, chemotherapy and without chemotherapy groups (P < .05), but not TOS (P > .05). In a receiver operating characteristic curve analysis comparing patients with lung cancer with healthy controls, the Youden indices of TOS, TAS, and OSI were 0.541, 0.532, and 1, respectively.The oxidative stress may be correlation with lung cancer staging. Smoking, surgery, radiotherapy, and chemotherapy showed correlation with parts oxidative stress parameters.


Assuntos
Antioxidantes/metabolismo , Neoplasias Pulmonares/sangue , Oxidantes/sangue , Biomarcadores Tumorais/sangue , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Curva ROC , Fumar/sangue
2.
Eur J Epidemiol ; 34(7): 637-649, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31037572

RESUMO

Ecological observations suggest an inverse relationship between smoking in pregnancy and celiac disease (CD) in offspring. While individual-level analyses have been inconsistent, they have mostly lacked statistical power or refined assessments of exposure. To examine the association between pregnancy-related smoking and CD in the offspring, as well as its consistency across data sets, we analyzed: (1) The Norwegian Mother and Child Cohort (MoBa) of 94,019 children, followed from birth (2000-2009) through 2016, with 1035 developing CD; (2) a subsample from MoBa (381 with CD and 529 controls) with biomarkers; and (3) a register-based cohort of 536,861 Norwegian children, followed from birth (2004-2012) through 2014, with 1919 developing CD. Smoking behaviors were obtained from pregnancy questionnaires and antenatal visits, or, in the MoBa-subsample, defined by measurement of cord blood cotinine. CD and potential confounders were identified through nationwide registers and comprehensive parental questionnaires. Sustained smoking during pregnancy, both self-reported and cotinine-determined, was inversely associated with CD in MoBa (multivariable-adjusted [a] OR = 0.61 [95%CI, 0.46-0.82] and aOR = 0.55 [95%CI, 0.31-0.98], respectively); an inverse association was also found with the intensity of smoking. These findings differed from those of our register-based cohort, which revealed no association with sustained smoking during pregnancy (aOR = 0.97 [95%CI, 0.80-1.18]). In MoBa, neither maternal smoking before or after pregnancy, nor maternal or paternal smoking in only early pregnancy predicted CD. In a carefully followed pregnancy cohort, a more-detailed smoking assessment than oft-used register-based data, revealed that sustained smoking during pregnancy, rather than any smoking exposure, predicts decreased likelihood of childhood-diagnosed CD.


Assuntos
Doença Celíaca/epidemiologia , Cotinina/sangue , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Celíaca/induzido quimicamente , Feminino , Sangue Fetal , Antígenos HLA , Humanos , Masculino , Pessoa de Meia-Idade , Mães , Noruega/epidemiologia , Gravidez , Sistema de Registros , Fatores de Risco , Autorrelato , Fumar/sangue , Abandono do Hábito de Fumar
3.
Artigo em Inglês | MEDLINE | ID: mdl-30939809

RESUMO

Environmental contaminants such as heavy metals are transported to the Arctic regions via atmospheric and ocean currents and enter the Arctic food web. Exposure is an important risk factor for health and can lead to increased risk of a variety of diseases. This study investigated the association between pregnant women's levels of heavy and essential metals and the birth outcomes of the newborn child. This cross-sectional study is part of the ACCEPT birth cohort (Adaption to Climate Change, Environmental Pollution, and dietary Transition) and included 509 pregnant Inuit women ≥18 years of age. Data were collected in five Greenlandic regions during 2010⁻2015. Population characteristics and birth outcomes were obtained from medical records and midwives, respectively, and blood samples were analyzed for 13 metals. Statistical analysis included one-way ANOVA, Spearman's rho, and multiple linear and logistic regression analyses. The proportion of current smokers was 35.8%. The levels of cadmium, chromium, and nickel were higher compared to reported normal ranges. Significant regional differences were observed for several metals, smoking, and parity. Cadmium and copper were significantly inversely related to birth outcomes. Heavy metals in maternal blood can adversely influence fetal development and growth in a dose⁻response relationship. Diet and lifestyle factors are important sources of toxic heavy metals and deviant levels of essential metals. The high frequency of smokers in early pregnancy is of concern, and prenatal exposure to heavy metals and other environmental contaminants in the Greenlandic Inuit needs further research.


Assuntos
Poluentes Ambientais/sangue , Desenvolvimento Fetal , Metais/sangue , Gravidez/sangue , Adolescente , Adulto , Peso ao Nascer , Estudos Transversais , Dieta , Feminino , Groenlândia , Humanos , Recém-Nascido , Inuítes , Fumar/sangue , Adulto Jovem
4.
Nat Commun ; 10(1): 1893, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015461

RESUMO

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.


Assuntos
Peso ao Nascer/genética , DNA/metabolismo , Epigênese Genética , Genoma Humano , Adolescente , Adulto , Índice de Massa Corporal , Criança , Ilhas de CpG , DNA/genética , Metilação de DNA , Feminino , Desenvolvimento Fetal/genética , Feto , Ácido Fólico/sangue , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fumar/efeitos adversos , Fumar/sangue , Fumar/genética
5.
Nat Commun ; 10(1): 1858, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015415

RESUMO

N6-methyladenosine (m6A) modification is an important mechanism in miRNA processing and maturation, but the role of its aberrant regulation in human diseases remained unclear. Here, we demonstrate that oncogenic primary microRNA-25 (miR-25) in pancreatic duct epithelial cells can be excessively maturated by cigarette smoke condensate (CSC) via enhanced m6A modification that is mediated by NF-κB associated protein (NKAP). This modification is catalyzed by overexpressed methyltransferase-like 3 (METTL3) due to hypomethylation of the METTL3 promoter also caused by CSC. Mature miR-25, miR-25-3p, suppresses PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2), resulting in the activation of oncogenic AKT-p70S6K signaling, which provokes malignant phenotypes of pancreatic cancer cells. High levels of miR-25-3p are detected in smokers and in pancreatic cancers tissues that are correlated with poor prognosis of pancreatic cancer patients. These results collectively indicate that cigarette smoke-induced miR-25-3p excessive maturation via m6A modification promotes the development and progression of pancreatic cancer.


Assuntos
Carcinoma Ductal Pancreático/patologia , Metiltransferases/metabolismo , MicroRNAs/metabolismo , Neoplasias Pancreáticas/patologia , Fumaça/efeitos adversos , Tabaco/toxicidade , Adenosina/análogos & derivados , Adenosina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/etiologia , Carcinoma Ductal Pancreático/mortalidade , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Proteínas Correpressoras/metabolismo , Metilação de DNA , Progressão da Doença , Células Epiteliais/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Masculino , Metiltransferases/genética , MicroRNAs/sangue , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Ductos Pancreáticos/citologia , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/mortalidade , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Prognóstico , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Fumar/efeitos adversos , Fumar/sangue , Regulação para Cima
6.
Toxicol Lett ; 311: 11-16, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31026483

RESUMO

4-(Methylnitrosamino)-l-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), two tobacco specific nitrosamine carcinogens, can form adducts with DNA and proteins via pyridyloxobutylation upon phase I enzyme-mediated bioactivation. Such DNA modifications have been proposed as the root cause to initiate carcinogenesis. Upon hydrolysis, both DNA and protein modifications would release 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB). The released HPB, being tobacco carcinogen specific, has the potential to serve as a surrogate biomarker for both tobacco exposure and carcinogen bioactivation. Because of its easy access, blood is a great source of such investigations with the potential in epidemiological application. HPB quantification from haemoglobin (Hb), however, has been demonstrated with limited success. To further explore this potentially paradigm-shift opportunity, we reported, for the first time, the detection and quantification of HPB from albumin (Alb) adducts formed by the tobacco-specific nitrosamines in mice and in human smokers. The time-course quantitative analysis of HPB from mouse Alb upon NNK exposure suggests that such an Alb adduct is stable. The amounts of HPB from Alb adducts in smoker plasma averaged 1.82 ± 0.19 pg/mg Alb (0.42 to 3.11 pg/mg Alb), which was 36 times the value in nonsmokers (0.05 ± 0.01 pg/mg Alb). Importantly, HPB level from Alb correlated positively with the level of human tobacco exposure estimated by urinary total nicotine equivalent (TNE) (R2 = 0.6170). For comparison, HPB level from Alb was 16.5 times that of Hb (0.12 ± 0.02 pg/mg Hb) in the plasma and red blood cell (RBC) samples of the same smokers. In addition, there was no significant correlation between HPB levels from Hb and TNE (R2 = 0.0719). These data overall suggest that HPB from Alb adducts can serve as a surrogate biomarker to monitor the level of tobacco exposure and carcinogenic nitrosamine bioactivation.


Assuntos
Butanonas/sangue , Nitrosaminas/metabolismo , Piridinas/sangue , Albumina Sérica/metabolismo , Fumar/sangue , Ativação Metabólica , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Hemoglobinas/metabolismo , Humanos , Modelos Animais , Nicotina/urina , Ligação Proteica , Fumar/efeitos adversos , Fumar/urina , Espectrometria de Massas em Tandem , Fatores de Tempo
7.
Nat Genet ; 51(4): 636-648, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30926973

RESUMO

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.


Assuntos
Lipídeos/sangue , Lipídeos/genética , Fumar/sangue , Fumar/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Estilo de Vida , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-30781849

RESUMO

(1) Background: Chronic obstructive pulmonary disease (COPD) is defined as an inflammatory disorder that presents an increasingly prevalent health problem. Accelerated aging has been examined as a pathologic mechanism of many chronic diseases like COPD. We examined whether COPD is combined with accelerated aging, studying two hormones, dehydroepiandrosterone (DHEA) and growth hormone (GH), known to be characteristic biological markers of aging. (2) Methods: Data were collected from 119 participants, 70 (58.8%) COPD patients and 49 (41.2%) from a health control group over the period of 2014⁻2016 in a spirometry program. Information about their medical history, tobacco use, and blood tests was obtained. (3) Results: The average age of the health control patients was 73.5 years (SD = 5.5), and that of the COPD patients was 75.4 years (SD = 6.9). Both groups were similar in age and sex. A greater proportion of smokers were found in the COPD group (87.1%) versus the control group (36.7%). The majority of COPD patients were classified as STAGE II (51.4%) and STAGE III (37.1%) according to GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease). Levels of DHEA (SD = 17.1) and GH (SD = 0.37) were significantly lower in the COPD group (p < 0.001) compared to those in the controls (SD = 26.3, SD = 0.79). DHEA and GH were more significant and negatively correlated with age. The regression equation of DHEA with age produced a coefficient equal to 1.26. In this study, the difference in DHEA between COPD patients and controls was, on average, 30.2 µg/dL, indicating that the biological age of a COPD patient is on average about 24 years older than that of a control subject of the same age. Similarly, the difference in GH between COPD patients and controls was, on average, 0.42 ng/mL, indicating that the biological age of a COPD patient is on average about 13.1 years older than that of a control subject of the same age. (4) Conclusions: The findings of our study strongly suggest the presence of premature biological aging in COPD patients. Their biological age could actually vary from 13 to 23 years older than non-COPD controls according to DHEA and GH variation.


Assuntos
Senilidade Prematura/complicações , Desidroepiandrosterona/sangue , Hormônio do Crescimento/sangue , Doença Pulmonar Obstrutiva Crônica/etiologia , Idoso , Idoso de 80 Anos ou mais , Senilidade Prematura/sangue , Senilidade Prematura/epidemiologia , Senilidade Prematura/fisiopatologia , Biomarcadores/sangue , Desidroepiandrosterona/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco , Fumar/sangue , Fumar/epidemiologia , Fumar/fisiopatologia , Espirometria
10.
Anal Bioanal Chem ; 411(11): 2351-2362, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30783713

RESUMO

Metabolism of chemicals from the diet, exposures to xenobiotics, the microbiome, and lifestyle factors (e.g., smoking, alcohol intake) produce electrophiles that react with nucleophilic sites in circulating proteins, notably Cys34 of human serum albumin (HSA). To discover potential risk factors resulting from in utero exposures, we are investigating HSA-Cys34 adducts in archived newborn dried blood spots (DBS) that reflect systemic exposures during the last month of gestation. The workflow includes extraction of proteins from DBS, measurement of hemoglobin (Hb) to normalize for blood volume, addition of methanol to enrich HSA by precipitation of Hb and other interfering proteins, digestion with trypsin, and detection of HSA-Cys34 adducts via nanoflow liquid chromatography-high-resolution mass spectrometry. As proof-of-principle, we applied the method to 49 archived DBS collected from newborns whose mothers either actively smoked during pregnancy or were nonsmokers. Twenty-six HSA-Cys34 adducts were detected, including Cys34 oxidation products, mixed disulfides with low molecular weight thiols (e.g., cysteine, homocysteine, glutathione, cysteinylglycine), and other modifications. Data were normalized with a novel method ("scone") to remove unwanted technical variation arising from HSA digestion, blood volume, DBS age, mass spectrometry analysis, and batch effects. Using an ensemble of linear and nonlinear models, the Cys34 adduct of cyanide was found to consistently discriminate between newborns of smoking and nonsmoking mothers with a mean fold change (smoking/nonsmoking) of 1.31. These results indicate that DBS adductomics is suitable for investigating in utero exposures to reactive chemicals and metabolites that may influence disease risks later in life.


Assuntos
Cisteína/análise , Teste em Amostras de Sangue Seco/métodos , Albumina Sérica Humana/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , Oxirredução , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Fumar/efeitos adversos , Fumar/sangue
11.
BMJ ; 364: k4981, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606716

RESUMO

OBJECTIVES: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. DESIGN: Nested case-control study. SETTING: 20 population based cohort studies in Asia, Europe, Australia, and the United States. PARTICIPANTS: 5299 patients with incident lung cancer, with individually incidence density matched controls. EXPOSURE: Circulating hsCRP concentrations in prediagnostic serum or plasma samples. MAIN OUTCOME MEASURE: Incident lung cancer diagnosis. RESULTS: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. CONCLUSIONS: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células Grandes/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Fumar/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Ex-Fumantes/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Razão de Chances , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Fumantes/estatística & dados numéricos , Fumar/epidemiologia , Adulto Jovem
12.
Clin Epigenetics ; 11(1): 1, 2019 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-30611298

RESUMO

BACKGROUND: DNA methylation alteration extensively associates with smoking and is a plausible link between smoking and adverse health. We examined the association between epigenome-wide DNA methylation and serum cotinine levels as a proxy of nicotine exposure and smoking quantity, assessed the role of SNPs in these associations, and evaluated molecular mediation by methylation in a sample of biochemically verified current smokers (N = 310). RESULTS: DNA methylation at 50 CpG sites was associated (FDR < 0.05) with cotinine levels, 17 of which are novel associations. As cotinine levels are influenced not only by nicotine intake but also by CYP2A6-mediated nicotine metabolism rate, we performed secondary analyses adjusting for genetic risk score of nicotine metabolism rate and identified five additional novel associations. We further assessed the potential role of genetic variants in the detected association between methylation and cotinine levels observing 124 cis and 3898 trans methylation quantitative trait loci (meQTLs). Nineteen of these SNPs were also associated with cotinine levels (FDR < 0.05). Further, at seven CpG sites, we observed a trend (P < 0.05) that altered DNA methylation mediates the effect of SNPs on nicotine exposure rather than a direct consequence of smoking. Finally, we performed replication of our findings in two independent cohorts of biochemically verified smokers (N = 450 and N = 79). CONCLUSIONS: Using cotinine, a biomarker of nicotine exposure, we replicated and extended identification of novel epigenetic associations in smoking-related genes. We also demonstrated that DNA methylation in some of the identified loci is driven by the underlying genotype and may mediate the causal effect of genotype on cotinine levels.


Assuntos
Cotinina/sangue , Metilação de DNA , Epigenômica/métodos , Polimorfismo de Nucleotídeo Único , Fumar/genética , Adulto , Idoso , Ilhas de CpG , Citocromo P-450 CYP2A6/genética , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/sangue , Adulto Jovem
13.
Psychiatry Res ; 272: 581-586, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30616127

RESUMO

This study aimed to examine the cross-sectional association of demographic and lifestyle factors with serum brain-derived neurotrophic factor (BDNF) concentrations in a Japanese working population. Participants were 1678 men and 172 women aged 19-69 years who received health check-ups and participated in a nutrition and health survey. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Dietary intake was assessed using a validated self-administered diet history questionnaire. Serum BDNF concentrations were measured using a solid phase sandwich enzyme-linked immunosorbent assay. Multiple linear regression analysis was used to estimate the mean and 95% confidence interval of serum BDNF concentrations according to demographic and lifestyle factors. Higher body mass index (BMI) was significantly associated with higher circulating BDNF concentrations. Current smokers had significantly higher mean BDNF concentrations than never-smokers. BDNF concentrations were not associated with folate and 25-hydroxyvitamin D concentrations in serum, or dietary eicosapentaenoic acid and docosahexaenoic acid intake. Serum BDNF concentrations were not associated with depressive symptoms or CES-D score per se. In this study, higher BMI and smoking were associated with higher concentrations of serum BDNF, while nutrients that have been linked to depression were not associated with BDNF concentrations among Japanese workers.


Assuntos
Índice de Massa Corporal , Fator Neurotrófico Derivado do Encéfalo/sangue , Emprego , Comportamento Alimentar/fisiologia , Estilo de Vida , Estado Nutricional/fisiologia , Fumar/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Emprego/tendências , Feminino , Inquéritos Epidemiológicos/métodos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Fumar/epidemiologia , Inquéritos e Questionários , Adulto Jovem
15.
Acta Diabetol ; 56(4): 473-479, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30635716

RESUMO

AIMS: Metabolic syndrome (MetS) is a cluster of risk factors for cardiometabolic diseases. While cigarette smoking is associated with MetS in adults, young adulthood is an under-studied, susceptible period for developing long-term morbidity from MetS. We examined associations between cigarette smoking and MetS risk factors. METHODS: We studied 430 participants in Santiago, Chile who have been followed in a longitudinal cohort since infancy and assessed in adolescence for MetS. Participants were evaluated at 22 years from May 2015 to July 2017. Adiposity, blood pressure, and blood samples were measured. MetS was defined using International Diabetes Federation criteria. A continuous MetS score was calculated using z-scores. Participants self-reported cigarette and alcohol consumption using standardized questionnaires. We used multivariate regressions to examine associations between smoking and MetS risk factors, adjusting for sex, MetS in adolescence, alcohol consumption, and socioeconomic status. RESULTS: Thirteen percent of participants had MetS and 50% were current smokers. Among smokers, mean age of initiation was 14.9 years and consumption was 29 cigarettes weekly. Smokers had larger waist circumferences, higher BMIs, and lower high-density lipoprotein (HDL) cholesterol compared to non-smokers. Being a current smoker was significantly associated with higher waist circumference (ß = 2.82; 95% CI 0.63, 5.02), lower HDL (ß = - 3.62; 95% CI - 6.19, - 1.04), higher BMI (ß = 1.22; 95% CI 0.16, 2.28), and higher MetS score (ß = 0.13, 95% CI 0.02, 0.24). CONCLUSIONS: Cigarette smoking at light levels (mean < 30 cigarettes weekly) was associated with MetS risk factors in a sample of Chilean young adults.


Assuntos
Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Chile/epidemiologia , HDL-Colesterol/sangue , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Síndrome Metabólica/sangue , Obesidade/sangue , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Fumar/sangue , Adulto Jovem
16.
Lipids Health Dis ; 18(1): 5, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30611277

RESUMO

OBJECTIVE: Coronary artery disease (CAD) is a multi-factor disease. Complement component 3 (C3) plays an important role in the development of CAD. The present study investigated the association between DNA methylation status of C3 gene promoter and the risk of CAD. METHODS: One hundred CAD patients and 1 hundred age-and gender- matched controls were recruited in current study. Methylation levels in CpG island in C3 promoter were determined by the method of bisulfite amplicon sequencing. RESULTS: Methylation levels of four CpG sites in C3 promoter were measured. There were no significant difference in methylation level of each CpG site between CAD patients and controls. Average methylation rate was also calculated. No significant difference in average methylation rate was observed between CAD and control groups. Stratified analyses based on EH, DM and smoking status were carried out, no significant association between C3 promoter methylation levels and the susceptibility of CAD was observed. Furthermore, seven haplotypes were established and no significant difference in haplotypes was observed between CAD and control groups. However, our study showed that C3 DNA methylation levels were positively associated with LDL-C levels. CONCLUSION: The present study showed no association between methylation levels of C3 promoter and the risk of CAD. However, the methylation levels might be related to LDL-C levels.


Assuntos
Complemento C3/genética , Doença da Artéria Coronariana/genética , Metilação de DNA , Epigênese Genética , Regiões Promotoras Genéticas , Idoso , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Complemento C3/imunologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/patologia , Ilhas de CpG , Diabetes Mellitus/sangue , Diabetes Mellitus/imunologia , Diabetes Mellitus/fisiopatologia , Feminino , Expressão Gênica , Haplótipos , Humanos , Hipertensão/sangue , Hipertensão/imunologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/sangue , Fumar/imunologia , Fumar/fisiopatologia , Triglicerídeos/sangue
17.
Respir Res ; 19(1): 257, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30563576

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established. METHODS: We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used the Sobel test to determine whether markers of systemic inflammation mediated a link between spirometric and radiographic features of COPD and CAC. RESULTS: FEV1/FVC but not quantitative emphysema or airway wall thickening was associated with CAC (p = 0.036), after adjustment for demographics, diabetes mellitus, hypertension, statin use, and CT scanner type. To explain this discordance, we examined visual subtypes of emphysema and airway disease, and found that centrilobular emphysema but not paraseptal emphysema or bronchial thickening was independently associated with CAC (p = 0.019). MMP3, VCAM1, CXCL5 and CXCL9 mediated 8, 8, 7 and 16% of the association between FEV1/FVC and CAC, respectively. Similar biomarkers partially mediated the association between centrilobular emphysema and CAC. CONCLUSIONS: The association between airflow obstruction and coronary calcification is driven primarily by the centrilobular subtype of emphysema, and is linked through bioactive molecules implicated in the pathogenesis of atherosclerosis. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT01969344 .


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/fisiopatologia , Enfisema Pulmonar/sangue , Enfisema Pulmonar/fisiopatologia , Calcificação Vascular/sangue , Calcificação Vascular/fisiopatologia , Idoso , Biomarcadores/sangue , Estudos de Coortes , Doença da Artéria Coronariana/diagnóstico , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados (Cuidados de Saúde)/métodos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/diagnóstico , Fumar/sangue , Fumar/fisiopatologia , Calcificação Vascular/diagnóstico , Capacidade Vital/fisiologia
18.
Respir Res ; 19(1): 256, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30563522

RESUMO

We performed a post-hoc analysis of the OLiVIA-study investigating whether current and ex-smoking asthmatics with small airways dysfunction (SAD) show a better response in airway hyperresponsiveness (AHR) to small particle adenosine after treatment with extrafine compared to non-extrafine particle inhaled corticosteroids (ICS), and to investigate which clinical parameters predict a favorable response to both treatments. We show that smoking and ex-smoking asthmatics with and without SAD have a similar treatment response with either extrafine or non-extrafine particle ICS. We also found that lower blood neutrophils are associated with a smaller ICS-response in smokers and ex-smokers with asthma, independent from the level of blood eosinophils.


Assuntos
Corticosteroides/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Ex-Fumantes , Tamanho da Partícula , Fumantes , Fumar/tratamento farmacológico , Administração por Inalação , Adulto , Remodelação das Vias Aéreas/efeitos dos fármacos , Remodelação das Vias Aéreas/fisiologia , Asma/sangue , Asma/diagnóstico , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fumar/sangue , Resultado do Tratamento
19.
Medicine (Baltimore) ; 97(49): e13216, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30544380

RESUMO

To determine whether glycated hemoglobin and mean arterial pressure (MAP) during thrombolysis are prognostic factors of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke (AIS).A total of 125 AIS patients, who received rt-PA intravenous thrombolysis in our hospital, were included into the present study, and divided into good prognosis group and poor prognosis group. Univariate and multivariate logistic regression analyses were used to determine the prognostic factors of AIS treated by rt-PA thrombolysis, Spearman correlation analysis was used to analyze the correlation of the accumulated cigarette consumption in the smoking subgroup and glycated hemoglobin in the diabetic subgroup with the prognosis after intravenous thrombolysis and the symptomatic intracranial hemorrhage (sICH).Univariate analysis revealed that the interval from onset to thrombolysis, baseline National Institutes of Health Stroke Scale (NIHSS) score, MAP during thrombolysis and DRAGON score were prognostic factors. Multivariate logistic regression analysis revealed that baseline NIHSS score and MAP during thrombolysis were independent prognostic factors for rt-PA thrombolysis. Furthermore, the glycated hemoglobin index was positively correlated with the incidence of sICH.The NIHSS score before thrombolysis and MAP during thrombolysis were independent factors for the prognosis of AIS treated by thrombolysis. The higher the glycated hemoglobin index of diabetic patients, the more likely they are to develop sICH, the glycated hemoglobin index was negatively correlated with the prognosis after intravenous thrombolysis. The accumulated cigarette consumption was negatively correlated with the prognosis after intravenous thrombolysis.


Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Administração Intravenosa , Adulto , Idoso , Pressão Arterial , Biomarcadores/sangue , Isquemia Encefálica/epidemiologia , Complicações do Diabetes/sangue , Complicações do Diabetes/epidemiologia , Feminino , Fibrinolíticos/uso terapêutico , Hemoglobinas/metabolismo , Humanos , Incidência , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes/uso terapêutico , Fumar/sangue , Fumar/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Ativador de Plasminogênio Tecidual/uso terapêutico
20.
Toxicol Lett ; 295: 307-313, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30010034

RESUMO

Diuron is a broad-spectrum phenylurea derived herbicide which is commonly used across the globe. Diuron is toxic to the reproductive system of animals and carcinogenic to rat urothelium, and recently found to be genotoxic in human cells. In in vivo, it is metabolized predominately into 3-(3,4-dichlorophenyl)-1-methyl urea (DCPMU) in humans and 3-(3, 4-dichlorophenyl)urea (DCPU) in animals. Information on diuron toxicokinetics and related toxicity in human placenta is absent. We have investigated the toxicokinetics of diuron in ex vivo human placental perfusion and in in vitro human placental microsomes and human trophoblastic cancer cells (BeWo). Diuron crossed human placenta readily in placental perfusion. Furthermore, diuron was metabolized into DCPMU in perfused placenta and in in vitro incubations using microsomes from placentas of smokers. In incubations with placental microsomes from non-smokers, and in BeWo cells, metabolism to DCPMU was detected but only with the highest used diuron concentration (100 µM). Diuron metabolism was inhibited upon addition of α-naphthoflavone, a CYP1A1 inhibitor, underscoring the role of CYP1A1 in the metabolism. In conclusion, it is evident that diuron crosses human placenta and diuron can be metabolized in the placenta to a toxic metabolite via CYP1A1. This implicates in vivo fetal exposure to diuron if pregnant women are exposed to diuron, which may result in fetotoxicity.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Diurona/sangue , Herbicidas/sangue , Troca Materno-Fetal , Placenta/irrigação sanguínea , Placenta/enzimologia , Circulação Placentária , Ativação Metabólica , Linhagem Celular Tumoral , Diurona/efeitos adversos , Feminino , Herbicidas/efeitos adversos , Humanos , Cinética , Microssomos/enzimologia , Gravidez , Medição de Risco , Fumar/efeitos adversos , Fumar/sangue , Toxicocinética
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