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1.
Pharmacol Res ; 191: 106749, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37004830

RESUMEN

Left congenital diaphragmatic hernia (CDH) can lead to pulmonary arteries abnormalities in the contralateral and ipsilateral sides of the diaphragm. Nitric oxide (NO) is the main therapy used to attenuate the vascular effects of CDH, but it is not always effective. We hypothesized that the left and right pulmonary arteries do not respond similarly to NO donors during CDH. Therefore, vasorelaxant responses of the left and right pulmonary arteries to sodium nitroprusside (SNP, a NO donor) were determined in a rabbit experimental model of left CDH. CDH was surgically induced in the fetuses of rabbits on the 25th day of pregnancy. On the 30th day of pregnancy, a midline laparotomy was performed to access the fetuses. The fetuses' left and right pulmonary arteries were isolated and mounted in myograph chambers. Vasodilation was evaluated by cumulative concentration-effect curves to SNP. Protein expression of guanylate cyclase isoforms (GCα, GCß) and the α isoform of cGMP-dependent protein kinase 1 (PKG1α), and the concentration of NO and cGMP were determined in the pulmonary arteries. The left and right pulmonary arteries of newborns with CDH exhibited increased vasorelaxant responses to SNP (i.e. the potency of SNP was increased) compared to the control group. GCα, GCß, and PKG1α expression were decreased, while NO and cGMP concentrations were increased in the pulmonary arteries of newborns with CDH compared to the control group. The increased cGMP mobilization may be responsible for the increased vasorelaxant responses to the SNP in the pulmonary arteries during left CDH.


Asunto(s)
Hernias Diafragmáticas Congénitas , Animales , Embarazo , Femenino , Conejos , Hernias Diafragmáticas Congénitas/metabolismo , Arteria Pulmonar , Óxido Nítrico/metabolismo , Pulmón , Vasodilatadores/farmacología
2.
Lancet Reg Health Am ; 14: 100328, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36777389

RESUMEN

Background: Congenital diaphragmatic hernia (CDH) is a severe embryological defect that causes pulmonary hypoplasia and hypertension. The prevalence and mortality rate of CDH varies around the world and little information is available about CDH in Latin America. Our aim was to estimate the general prevalence, mortality rate, prevalence of associated anomalies and features related to the outcomes of CDH in newborns from São Paulo state, Brazil. Methods: Population-based cross-sectional study based on data gathered from the Live Births Information System (SINASC) and the Mortality Information System (SIM) of children born in São Paulo state between January 1st, 2006, and December 31st, 2017. Findings: From 7,311,074 total survival discharges between 2006 and 2017, 1,155 were CDH-related, resulting in a prevalence rate of 1:6329 (95%CI = 1/6715 - 1/5984) and a mortality rate of 63·72% (95%CI = 60.95 - 66.50), 510 presented complex associated anomalies (44·15%). Maternal data showed higher prevalence among older mothers (older than 35 years old: 2·13 per 10,000) and, also, women with more years of schooling (higher than 12 years: 1·99 per 10,000). Presence of associated anomalies (95%CI = 5.69-11.10), 1-min Apgar (95%CI = 1.44-2.95), maternal schooling (95%CI = 1.06-2.43) and birth weight (95%CI = 1.04-2.26) were the most significant features associated with mortality. Interpretation: There was 1 CDH case for every 6329 newborns in São Paulo and the mortality rate among those cases was 63·72% - a high rate compared to other countries. Funding: This study didn't receive any specific grant from any funding agency in the public, commercial or not-for-profit sectors.

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