Increased arterial endothelial cell permeability (ECP) is considered an initial step in atherosclerosis. Atrial natriuretic peptide (ANP) which is rapidly degraded by neprilysin (NEP) may reduce injury-induced endothelial cell leakiness. Omapatrilat represents a first in class of pharmacological agents which inhibits both NEP and angiotensin converting enzyme (ACE). We hypothesized that ANP prevents thrombin-induced increases of ECP in human aortic ECs (HAECs) and that omapatrilat would reduce aortic leakiness and atherogenesis and enhance ANP mediated vasorelaxation of isolated aortas. Thrombin induced ECP determined by I 125 albumin flux was assessed in HAECs with and without ANP pretreatment. Next we examined the effects of chronic oral administration of omapatrilat (12mg/kg/day, n=13) or placebo (n=13) for 8 weeks on aortic leakiness, atherogenesis and ANP-mediated vasorelaxation in isolated aortas in a rabbit model of atherosclerosis produced by high cholesterol diet. In HAECs, thrombin-induced increases in ECP were prevented by ANP. Omapatrilat reduced the area of increased aortic leakiness determined by Evans-blue dye and area of atheroma formation assessed by Oil-Red staining compared to placebo. In isolated arterial rings, omapatrilat enhanced vasorelaxation to ANP compared to placebo with and without the endothelium. ANP prevents thrombin-induced increases in ECP in HAECs. Chronic oral administration of omapatrilat reduces aortic leakiness and atheroma formation with enhanced endothelial independent vasorelaxation to ANP. These studies support the therapeutic potential of dual inhibition of NEP and ACE in the prevention of increased arterial ECP and atherogenesis which may be linked to the ANP/cGMP system.
Highlights
PTLD develops after transplantation, because of the immunosuppressive therapy.
PTLD of the genital tract is very rare case.
PTLD has a poor prognosis.
PTLD may increase in the future with progress of transplantation medicine.
Gynecologists should consider the presence of PTLD.
Objectives:To evaluate the diagnostic accuracy of prenatal screening for congenital heart diseases (CHD) based on the combination of the four-chamber view and the three-vessel view in an unselected population. Methods: A prospective study on 8025 scanned fetuses was performed. All singleton pregnancies scheduled for a routine prenatal ultrasound screening at 20-24 weeks' gestation and subsequently delivered within our unit were included. Data were recorded regarding visualization of the four-chamber view, the outflow tracts and the three-vessel view. Suspected CHD was confirmed by postmortem or postnatal echocardiography. We obtained the followup data of the newborns and calculated the diagnostic accuracy of the test. Results: Major CHD were identified in 32 cases (4.0‰) of which 26 cases (81.3%) were diagnosed antenatally and 6 postnatally. Four cases were false positive. Twenty-one cases were identified by the four-chamber view and five as a result of the abnormal three-vessel view. The sensitive of the four-chamber view alone was 65.6% (17/32), and the specificity was 99.9%. The sensitivity of the combination of the four-chamber view and the three-vessel view was 81.3% (26/32), and the specificity was 99.9%.
Conclusions:The three-vessel view is reliable and easy methods to be used in a routine antenatal clinic, along with the four-chamber view.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.