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1.
Alcohol Clin Exp Res ; 45(1): 69-78, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33206417

RESUMO

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is caused by prenatal alcohol exposure (PAE), the intake of ethanol (C2 H5 OH) during pregnancy. Features of FASD cover a range of structural and functional defects including congenital heart defects (CHDs). Folic acid and choline, contributors of methyl groups to one-carbon metabolism (OCM), prevent CHDs in humans. Using our avian model of FASD, we have previously reported that betaine, another methyl donor downstream of choline, prevents CHDs. The CHD preventions are substantial but incomplete. Ethanol causes oxidative stress as well as depleting methyl groups for OCM to support DNA methylation and other epigenetic alterations. To identify more compounds that can safely and effectively prevent CHDs and other effects of PAE, we tested glutathione (GSH), a compound that regulates OCM and is known as a "master antioxidant." METHODS/RESULTS: Quail embryos injected with a single dose of ethanol at gastrulation exhibited congenital defects including CHDs similar to those identified in FASD individuals. GSH injected simultaneously with ethanol not only prevented CHDs, but also improved survival and prevented other PAE-induced defects. Assays of hearts at 8 days (HH stage 34) of quail development, when the heart normally has developed 4-chambers, showed that this single dose of PAE reduced global DNA methylation. GSH supplementation concurrent with PAE normalized global DNA methylation levels. The same assays performed on quail hearts at 3 days (HH stage 19-20) of development, showed no difference in global DNA methylation between controls, ethanol-treated, GSH alone, and GSH plus ethanol-treated cohorts. CONCLUSIONS: GSH supplementation shows promise to inhibit effects of PAE by improving survival, reducing the incidence of morphological defects including CHDs, and preventing global hypomethylation of DNA in heart tissues.


Assuntos
Metilação de DNA/efeitos dos fármacos , Transtornos do Espectro Alcoólico Fetal/prevenção & controle , Glutationa/uso terapêutico , Cardiopatias Congênitas/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal , Consumo de Bebidas Alcoólicas/efeitos adversos , Animais , Depressores do Sistema Nervoso Central/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Etanol/efeitos adversos , Feminino , Glutationa/farmacologia , Cardiopatias Congênitas/induzido quimicamente , Gravidez , Codorniz
2.
Alcohol Clin Exp Res ; 41(11): 1917-1927, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28888041

RESUMO

BACKGROUND: Despite decades of public education about dire consequences of prenatal alcohol exposure (PAE), drinking alcohol during pregnancy remains prevalent. As high as 40% of live-born infants exposed to alcohol during gestation and diagnosed with fetal alcohol syndrome have congenital heart defects that can be life-threatening. In animal models, the methyl donor betaine, found in foods such as wheat bran, quinoa, beets, and spinach, ameliorated neurobehavioral deficits associated with PAE, but effects on heart development are unknown. METHODS: Previously, we modeled a binge drinking episode during the first trimester in avian embryos. Here, we investigated whether betaine could prevent adverse effects of alcohol on heart development. Embryos exposed to ethanol (EtOH) with and without an optimal dose of betaine (5 µM) were analyzed at late developmental stages. Cardiac morphology parameters were rapidly analyzed and quantified using optical coherence tomography. DNA methylation at early stages was detected by immunofluorescent staining for 5-methylcytosine in sections of embryos treated with EtOH or cotreated with betaine. RESULTS: Compared to EtOH-exposed embryos, betaine-supplemented embryos had higher late-stage survival rates and fewer gross head and body defects than seen after alcohol exposure alone. Betaine also reduced the incidence of late-stage cardiac defects such as absent vessels, abnormal atrioventricular (AV) valves, and hypertrophic ventricles. Furthermore, betaine cotreatment brought measurements of great vessel diameters, interventricular septum thickness, and AV leaflet volumes in betaine-supplemented embryos close to control values. Early-stage 5-methycytosine staining revealed that DNA methylation levels were reduced by EtOH exposure and normalized by co-administration with betaine. CONCLUSIONS: This is the first study demonstrating efficacy of the methyl donor betaine in alleviating cardiac defects associated with PAE. These findings highlight the therapeutic potential of low-concentration betaine doses in mitigating PAE-induced birth defects and have implications for prenatal nutrition policies, especially for women who may not be responsive to folate supplementation.


Assuntos
Betaína/administração & dosagem , Etanol/toxicidade , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Animais , Coturnix , Suplementos Nutricionais , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/fisiologia , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem
3.
Echocardiography ; 29(10): E267-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22957823

RESUMO

Superior vena cava aneurysm is a rare intrathoracic vascular lesion with only 27 cases reported in the literature. The majority are fusiform and can be associated with cystic hygroma due to the close embryonic relationship between lymphatic vessels and systemic veins. This is the first report of superior vena cava aneurysm diagnosed with fetal echocardiography in a fetus with a cystic hygroma. There is a need of a prospective registry to further delineate all aspects of this condition and establish the most appropriate therapeutic approach.


Assuntos
Aneurisma/diagnóstico por imagem , Ecocardiografia/métodos , Ultrassonografia Pré-Natal/métodos , Veia Cava Superior/diagnóstico por imagem , Adulto , Aneurisma/embriologia , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Gravidez , Veia Cava Superior/embriologia
4.
Tex Heart Inst J ; 43(6): 546-549, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28100981

RESUMO

Isolated left subclavian artery is one of the rarer aortic arch anomalies. It has been associated with other congenital heart diseases, typically tetralogy of Fallot, double-outlet right ventricle, and atrial and ventricular septal defects. Its significant clinical implications include a left-to-right shunt from the vertebrobasilar system, which causes pulmonary overcirculation and subclavian steal. We present an unusual case of a premature infant who was diagnosed prenatally with congenital complete atrioventricular block and tricuspid atresia and was found to have an isolated left subclavian artery postnatally. The patient underwent implantation of a permanent single-chamber epicardial pacing system. To our knowledge, this combination of lesions has not been reported-and in our case, it influenced our surgical planning.


Assuntos
Anormalidades Múltiplas , Bloqueio Atrioventricular/congênito , Bloqueio Cardíaco/congênito , Artéria Subclávia/anormalidades , Atresia Tricúspide/complicações , Malformações Vasculares/complicações , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/cirurgia , Estimulação Cardíaca Artificial , Angiografia por Tomografia Computadorizada , Ecocardiografia Doppler em Cores , Desenho de Equipamento , Feminino , Técnica de Fontan , Idade Gestacional , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/cirurgia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Marca-Passo Artificial , Artéria Pulmonar/anormalidades , Artéria Pulmonar/diagnóstico por imagem , Reimplante , Artéria Subclávia/diagnóstico por imagem , Artéria Subclávia/cirurgia , Resultado do Tratamento , Atresia Tricúspide/diagnóstico por imagem , Atresia Tricúspide/cirurgia , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/cirurgia
5.
Tex Heart Inst J ; 43(5): 430-432, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27777530

RESUMO

We report a rare causal association between obstructed supracardiac totally anomalous pulmonary venous drainage and coronary sinus ostial atresia. Our 12-week-old patient developed venous myocardial infarction secondary to coronary venous hypertension because her sole route of coronary venous drainage was obstructed. She recovered after the obstruction was relieved by balloon dilation. Surgical repair then included anastomosis of the pulmonary venous confluence to the left atrium, ligation of the vertical vein, and unroofing of the coronary sinus. Coronary sinus ostial atresia is rarely diagnosed before autopsy.


Assuntos
Anormalidades Múltiplas , Seio Coronário/anormalidades , Anomalias dos Vasos Coronários/complicações , Hipertensão Pulmonar/etiologia , Infarto do Miocárdio/etiologia , Síndrome de Cimitarra/complicações , Angioplastia Coronária com Balão , Procedimentos Cirúrgicos Cardíacos , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Circulação Coronária , Seio Coronário/diagnóstico por imagem , Seio Coronário/fisiopatologia , Seio Coronário/cirurgia , Anomalias dos Vasos Coronários/diagnóstico por imagem , Anomalias dos Vasos Coronários/fisiopatologia , Anomalias dos Vasos Coronários/cirurgia , Ecocardiografia Doppler em Cores , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Lactente , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Síndrome de Cimitarra/diagnóstico por imagem , Síndrome de Cimitarra/fisiopatologia , Síndrome de Cimitarra/cirurgia , Resultado do Tratamento , Pressão Venosa
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