RESUMO
La epilepsia engloba un conjunto de trastornos convulsivos heterogéneos, con diversas características clínicas que excluyen un mecanismo etiológico singular. Individuos con epilepsia presentan una tasa significativamente mayor de condiciones psiquiátricas y neurológicas asociadas. Niños con epilepsia tienen dos a tres veces más riesgo de desarrollar trastornos por déficit de atención e hiperactividad (TDAH) cuando son comparados con individuos sanos, mientras que uno de cada cinco adultos epilépticos presentan síntomas de TDAH. En los niños con epilepsia, la gravedad y frecuencia de las crisis y una edad más temprana de inicio de las crisis son factores de riesgo comunes para padecer TDAH. Se realizó una revisión narrativa de la literatura y se seleccionaron artículos publicados en el periodo entre el año 2003 y 2021 en bases digitales del área de la salud (LILACS, Medline, Web of Science, SciELO y PubMed). La revisión evidenció que la epilepsia puede aumentar el riesgo de desarrollar TDAH en los niños, y que la epilepsia rolándica benigna es el tipo más diagnosticado en estos niños, que incluso tiene alta tasa de trastornos neuroconductuales con síntomas de TDAH asociados. El diagnóstico temprano y un manejo apropiado, llevan a mejor pronóstico en este grupo de pacientes
Epilepsy encompasses a set of heterogeneous seizure disorders, with various clinical characteristics that exclude a unique etiological mechanism. Individuals with this disease have a significantly higher rate for the development of psychiatric and neurological conditions. Children with epilepsy have two to three times increased risk of developing ADHD when compared to healthy individuals, while one in five epileptic adults have ADHD symptoms. In children with epilepsy, the severity and frequency of seizures and an earlier age at the onset of seizures are common risk factors for ADHD. A narrative review of the literature was carried out and articles published in the period between 2003 and 2021 in digital databases of the health area (LILACS, Medline, Web of Science, SciELO and PubMed) were selected. The review showed that epilepsy can increase the risk of developing ADHD in children, and that benign rolandic epilepsy is the most diagnosed type in these children, which even has a high rate of neurobehavioral disorders with associated ADHD symptoms. Early diagnosis and appropriate management lead to a better prognosis in this group of patients.
Assuntos
Humanos , Criança , Transtorno do Deficit de Atenção com Hiperatividade , EpilepsiaRESUMO
Focal adhesion kinase (FAK) has emerged as a mediator of mechanotransduction in cardiomyocytes, regulating gene expression during hypertrophic remodeling. However, how FAK signaling is relayed onward to the nucleus is unclear. Here, we show that FAK interacts with and regulates myocyte enhancer factor 2 (MEF2), a master cardiac transcriptional regulator. In cardiomyocytes exposed to biomechanical stimulation, FAK accumulates in the nucleus, binds to and upregulates the transcriptional activity of MEF2 through an interaction with the FAK focal adhesion targeting (FAT) domain. In the crystal structure (2.9 Å resolution), FAT binds to a stably folded groove in the MEF2 dimer, known to interact with regulatory cofactors. FAK cooperates with MEF2 to enhance the expression of Jun in cardiomyocytes, an important component of hypertrophic response to mechanical stress. These findings underscore a connection between the mechanotransduction involving FAK and transcriptional regulation by MEF2, with potential relevance to the pathogenesis of cardiac disease.
Assuntos
Quinase 1 de Adesão Focal/química , Mecanotransdução Celular , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-jun/química , Transcrição Gênica , Motivos de Aminoácidos , Animais , Animais Recém-Nascidos , Sítios de Ligação , Linhagem Celular , Núcleo Celular/metabolismo , Clonagem Molecular , Cristalografia por Raios X , Escherichia coli/genética , Escherichia coli/metabolismo , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Expressão Gênica , Regulação da Expressão Gênica , Cinética , Fatores de Transcrição MEF2/química , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/metabolismo , Camundongos , Modelos Moleculares , Miócitos Cardíacos/citologia , Cultura Primária de Células , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Ratos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
INTRODUCTION: Polychlorinated biphenyls (PCBs), used as pesticides in agriculture, can lead to irreversible injuries in living organisms, particularly in liver. Oxidative stress has been implicated in the liver pathogenesis induced by different molecules, including PCBs. It has been demonstrated that quercetin, an antioxidant flavonoid found in the diet, exhibits a potent antioxidant effect in different liver pathologies. OBJECTIVE: To evaluate oxidative stress caused by PCBs in liver and the antioxidant activity of quercetin. METHODOLOGY: We used male Wistar rats (n = 36), divided in 4 groups: control, quercetin (50 mg/kg/day), PCBs (0.4 ml/kg/day), and rats treated with both PCBs and quercetin. On day 25 blood was collected to assess liver integrity (enzymes AST, ALT and ALP), and liver samples to measure oxidative stress (TBARS), activity of antioxidant enzymes (SOD, CAT, GPx) and DNA damage (micronucleus assay), and histological damage. RESULTS: TBARS concentration and SOD activity were significantly higher in PCBs animals as compared to the PCB group receiving quercetin. CAT and GPx decreased in PCBs and increased when quercetin was added. The histological analysis showed damage to hepatocytes in PCBs, but quercetin was able to afford protection against such damage. The micronucleus test showed there was an increase in the production of microclenucleus compared to control, and quercetin was able to reduce this effect. CONCLUSION: Contamination with PCBs led to increased lipid peroxidation and DNA damage, and the use of antioxidant quercetin was effective in reducing PCBs-induced liver injury.
Introducción: los bifenilospoliclonados (PCBs) son pesticidas ampliamente usados en agricultura que pueden inducir daños irreversibles particularmente en el hígado. El estrés oxidativo ha sido implicado en diversas patogénesis hepáticas, incluidas las relacionadas conPCBs. La quercetina, un flavonoide de la dieta, ha demostrado tener un potente efecto antioxidante en diversos modelos de patología hepática. Objetivo: Evaluar el estrés oxidativo hepático inducido por PCBs y la actividad antioxidante de la quercetina. Metodología: Se usaron ratas macho de raza Wistar (n = 36), divididas en cuatro grupos: control, quercetina (50 mg/kg/día), PCBs (0,4 ml/kg/día) y ratas tratadas tanto con PCBs como con quercetina. Transcurridos 25 días de tratamiento se recogieron muestras de sangre, para evaluar la integridad hepática (AST, ALT y ALP), y de tejido para cuantificar el estrés oxidativo (TBARS), actividad antioxidante (SOD, CAT, GPx), daño al DNA (ensayo de micronúcleos) y daño histológico. Resultados: la concentración de TBARS y la actividad SOD fueron significativamente mayores en los animales que recibieron PCBs que en los que recibían quercetina. La actividad de CAT y GPx se redujo con los PCBs y se incrementó al administrar quercetina. Los análisis histológicos y de micronúcleos mostraron daño hepático y al DNA respectivamente inducido por PCBs que eran revertidos con el tratamiento con quercetina. Conclusion: La contaminación con PCBs induce un incremento en la peroxidación lipídica, modificación en la actividad de enzimas antioxidantes, daño histológico y al DNA en el hígado, siendo el antioxidante quercetina es capaz de reducir dichos cambios.