RESUMO
Intrauterine growth restriction (IUGR) is a condition which has been difficult to assess at an early stage, resulting in the delivery of children who have poor genetic growth potential. Currently, IUGR classification is based upon the system of ultrasound biometry. Doppler velocimetry allows the measurement of hemodynamic flow of major fetal vessels, comparing the flow indices and patterns of normal and IUGR cases. In this review, the effectiveness of Doppler velocimetry in assessing blood flow in major vessels including the umbilical artery, ductus venosus, and middle cerebral artery was studied for both diagnostic and prognostic screening of IUGR. The umbilical artery is the most frequently studied vessel in Doppler velocimetry due to its accessibility and the strength of its associations with fetal outcomes. Abnormalities in the ductus venosus waveform can be indicative of increased resistance in the right atrium due to placental abnormalities. The middle cerebral artery is the most studied fetal cerebral artery and can detect cerebral blood flow and direction, which is why these three vessels were selected to be examined in this context. A potential mathematical model could be developed to incorporate these Doppler measurements which are indicative of IUGR, in order to reduce perinatal mortality. The purpose of the proposed algorithm is to integrate Doppler velocimetry with biophysical profiling in order to determine the optimal timing of delivery, thus reducing the risks of adverse perinatal outcomes.
Assuntos
Retardo do Crescimento Fetal/diagnóstico por imagem , Fluxometria por Laser-Doppler , Artéria Cerebral Média/diagnóstico por imagem , Placenta/irrigação sanguínea , Ultrassonografia Pré-Natal , Artérias Umbilicais/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Hemodinâmica , Humanos , Recém-Nascido , Artéria Cerebral Média/embriologia , Oxigênio/metabolismo , Gravidez , Prognóstico , Artérias Umbilicais/embriologiaRESUMO
This study explores and characterizes the toxicity of two closely related carcinogenic dinitro-pyrenes (DNPs), 1,3-DNP and 1,8-DNP, in human bronchial epithelial BEAS-2B cells and mouse hepatoma Hepa1c1c7 cells. Neither 1,3-DNP nor 1,8-DNP (3-30 µM) induced cell death in BEAS-2B cells. In Hepa1c1c7 cells only 1,3-DNP (10-30 µM) induced a mixture of apoptotic and necrotic cell death after 24 h. Both compounds increased the level of reactive oxygen species (ROS) in BEAS-2B as measured by CM-H2DCFDA-fluorescence. A corresponding increase in oxidative damage to DNA was revealed by the formamidopyrimidine-DNA glycosylase (fpg)-modified comet assay. Without fpg, DNP-induced DNA damage detected by the comet assay was only found in Hepa1c1c7 cells. Only 1,8-DNP formed DNA adduct measured by 32P-postlabelling. In Hepa1c1c cells, 1,8-DNP induced phosphorylation of H2AX (γH2AX) and p53 at a lower concentration than 1,3-DNP and there was no direct correlation between DNA damage/DNA damage response (DR) and induced cytotoxicity. On the other hand, 1,3-DNP-induced apoptosis was inhibited by pifithrin-α, an inhibitor of p53 transcriptional activity. Furthermore, 1,3-DNP triggered an unfolded protein response (UPR), as measured by an increased expression of CHOP, ATF4 and XBP1. Thus, other types of damage possibly linked to endoplasmic reticulum (ER)-stress and/or UPR could be involved in the induced apoptosis. Our results suggest that the stronger carcinogenic potency of 1,8-DNP compared to 1,3-DNP is linked to its higher genotoxic effects. This in combination with its lower potency to induce cell death may increase the probability of causing mutations.