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3.
J Trace Elem Med Biol ; 55: 110-120, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345348

RESUMO

The developmental period in utero is a critical window for environmental exposure. Epigenetic fetal programming via DNA methylation is a pathway through which metal exposure influences the risk of developing diseases later in life. Genetic damage repair can be modified by alterations in DNA methylation, which, in turn, may modulate gene expression due to metal exposure. We investigated the impact of prenatal metal exposure on global and gene-specific DNA methylation and mRNA expression in 181 umbilical cord blood samples from newborns in Mexico City. Global (LINE1) and promoter methylation of DNA-repair (OGG1 and PARP1) and antioxidant (Nrf2) genes was evaluated by pyrosequencing. Prenatal metal exposure (As, Cu, Hg, Mn, Mo, Pb, Se, and Zn) was determined by ICP-MS analysis of maternal urine samples. Multiple regression analyses revealed that DNA methylation of LINE1, Nrf2, OGG1, and PARP1 was associated with potentially toxic (As, Hg, Mn, Mo, and Pb) and essential (Cu, Se, and Zn) elements, and with their interactions. We also evaluated the association between gene expression (mRNA levels quantified by p-PCR) and DNA methylation. An increase in OGG1 methylation at all sites and at CpG2, CpG3, and CpG4 sites was associated with reduced mRNA levels; likewise, methylation at the CpG5, CpG8, and CpG11 sites of PARP1 was associated with reduced mRNA expression. In contrast, methylation at the PARP1 CpG7 site was positively associated with its mRNA levels. No associations between Nrf2 expression and CpG site methylation were observed. Our data suggest that DNA methylation can be influenced by prenatal metal exposure, which may contribute to alterations in the expression of repair genes, and therefore, result in a lower capacity for DNA damage repair in newborns.


Assuntos
Antioxidantes/metabolismo , Metilação de DNA/efeitos dos fármacos , Reparo do DNA/genética , Metais Pesados/farmacologia , População Urbana , Adolescente , Adulto , Dano ao DNA , DNA Glicosilases/genética , Feminino , Humanos , Recém-Nascido , Metais Pesados/administração & dosagem , México , Fator 2 Relacionado a NF-E2/genética , Poli(ADP-Ribose) Polimerase-1/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , Adulto Jovem
4.
Med. intensiva (Madr., Ed. impr.) ; 29(7): 379-383, oct. 2005. tab, graf
Artigo em Es | IBECS | ID: ibc-040203

RESUMO

Objetivo. Analizar la frecuencia, la etiología, la asociación con arritmias y la mortalidad del síndrome de QT largo (SQTL) adquirido en la Unidad de Cuidados Intensivos (UCI). Diseño. Estudio retrospectivo.Ámbito. Una UCI médica de 17 camas. Pacientes y método. Pacientes ingresados en la UCI entre enero de 1997 y julio de 2004 que desarrollaron SQTL. Se consideró SQTL un QT largo para la frecuencia cardíaca o un QT corregido (QTc) > 0,45 segundos en hombres o > 0,46 segundos en mujeres. Variables de interés principales. Las variables estudiadas fueron edad, género, motivo de ingreso, cardiopatía asociada, asociación a fármacos y clase implicada, presencia de arritmias y tratamiento empleado, mortalidad en la UCI. Resultados. Se incluyeron 88 pacientes (48 mujeres y 40 hombres con edad media de 55,8 ± 19,8 años). El principal motivo de ingreso fue la intoxicación medicamentosa. La etiología se asoció a fármacos en 54 casos (61,4%), siendo los más frecuentemente asociados: psicotropos, 41 ocasiones (75,9%), antiarrítmicos, 22 (40,7%), antimicrobianos, 4 (7,4%) y otros, 6 (11,1%). El 50% de los pacientes mostró alguna arritmia, siendo la taquicardia ventricular (TV) la más frecuente en 26 ocasiones (59,1%), seguida de torsades de Pointes (TdP) en 15 casos (34,1%). Esta arritmia fue significativamente más frecuente en el sexo femenino. Precisaron tratamiento 53 pacientes (60,2%), de ellos 29 (33%) recibieron tratamiento iónico, 14 (26,4%) sobreestimulación con marcapasos y 15 (17%) necesitaron cardioversión. La mortalidad fue del 6,8%. Conclusiones. Los psicofármacos, fundamentalmente los antidepresivos, son los más frecuentemente relacionados con SQTL en nuestro medio. La arritmia más frecuente es la TV


Objective. Analyze the frequency, etiology, association with arrhythmias and mortality of long QT syndrome (LQTS) acquired in the Intensive Care Unit (ICU).Design. Retrospective study.Scope. A 17-bed medical ICU.Patients and methods. Patients admitted to the ICU between January 1997 and July 2004 who developed LQTS. LQTS was considered to be a long QT for the heart rate or corrected QT (QTc) > 0.45 seconds in men and > 0.46 seconds in women.Principal variables of interest. The variables studied were age, gender, reason for admission, associated heart disease, association to drugs and class involved, presence of arrhythmias and treatment used, mortality in ICU. Results. A total of 88 patients (48 women and 40 men with mean age of 55.8 ± 19.8 years) were included. The main reason for admission was drug poisoning. The etiology was associated to drugs in 54 cases (61.4%), the most frequently associated ones being: psychotropics, 41 times (75.9%), antiarrhythmics, 22 (40.7%), antimicrobial, 4 (7.4%) and others, 6 (11.1%). A total of 50% of the patients showed some arrhythmia, ventricular tachycardia (VT) being the most frequent in 26 occasions (59.1%), followed by torsades de Pointes (TdP) in 15 cases (34.1%). This arrhythmia was significantly more frequent in the female gender. A total of 53 patients (60.2%) required treatment. Twenty nine (33%) of them received ionic treatment, 14 (26.4%) overstimulation with pacemakers and 15 (17%) needed cardioversion. Mortality was 6.8%. Conclusions. Psychodrugs, basically antidepressives, are the most frequently related with LQTS in our setting. The most frequent arrhythmia is VT


Assuntos
Masculino , Feminino , Adulto , Idoso , Adolescente , Pessoa de Meia-Idade , Humanos , Síndrome do QT Longo/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Síndrome do QT Longo/etiologia , Estudos Retrospectivos , Torsades de Pointes/epidemiologia , Arritmias Cardíacas/epidemiologia , Fatores de Risco , Eletrocardiografia
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