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At 32 weeks of gestation, a male fetus with congenitally corrected transposition of the great arteries developed hydrops fetalis caused by a combination of mitral valve regurgitation and tricuspid valve regurgitation (TR). We performed a pulmonary artery banding (PAB) at 108 days old for gradually progressing TR, after confirming that a balloon dilatation test in the main pulmonary artery reduced TR. As the patient grew, the PAB became tighter and systolic blood pressure in the morphological left ventricle increased. At present, the patient is waiting for a double switch operation.

Background:Virus-associated acute encephalopathy (VAE) is a severe central nervous system complication caused by common viral infections in children. The pathophysiology of VAE is thought to be endothelial injury. This study was designed to establish an in vitro VAE model for evaluating endothelial injury caused by the proinflammatory cytokine TNF-α.Methods:Transwell-grown human umbilical vein endothelial cells (HUVECs) monolayers were incubated with serially diluted TNF-α. Transendothelial electrical resistance (TER) was measured using impedance spectroscopy. Permeability changes of HUVECs after TNF-α treatment were determined by fluorescein isothiocyanate (FITC)-conjugated dextran. Moreover, TNF-α-induced morphological changes in claudin-5 and apoptosis were observed by immunofluorescent staining.Results:The decrease in TER, time of TER recovery to baseline, and increase in permeability were all dependent on TNF-α concentration. Immunofluorescent staining showed that claudin-5 was delocalized after TNF-α treatment in a dose-dependent manner. In addition, some apoptotic cells were observed at high TNF-α concentrations.Conclusion:TER measurement combined with a permeability assay could be useful for evaluating vascular endothelial cell permeability in an in vitro model. These evaluation methods will contribute to both the development of specific treatments focusing on vascular permeability, and the search for a novel therapeutic strategy in VAE treatment.

AbstractBackground:Although glucocorticoid hormones play important roles in fetal development, the expression of their receptors in the whole blood of preterm infants remains unknown.Objectives:The aim of this study was to investigate the levels of glucocorticoid receptor (GR) α and β in the whole blood of preterm and term infants.Study design:The study group consisted of 131 infants, of which 54 (41%) were preterm. Whole blood from preterm and term infants was analyzed by real-time PCR to monitor the levels of each receptor mRNA.Results:GRβ mRNA were detected in 96.6% and GRα mRNA in 100% of participants. The GRα and GRβ isoforms were detected at a ratio of 1:0.0002. GRβ mRNA/GAPDH expression in preterm infants was significantly higher than that in term infants (p=0.002). There was significant correlation between GRα/GRβ ratio and birth weight in preterm infants (rs=0.317, p=0.019), as well as between GRβ/GAPDH expression and birth weight (rs=–0.296, p=0.030). Furthermore, in preterm infants, GRβ/GAPDH expression was higher in those with SGA than in those without SGA (p=0.022).Conclusion:Importantly, in preterm infants, both the expression of GRβ and the GRα/GRβ ratio were associated with birth weight. Further studies with larger populations are necessary to determine the relation between the expression of GR and the clinical relevance of preterm infants.

Newborn animals are more resistant to anoxia than older animals, partly due to an increased tolerance of the immature heart to anoxia. Newborn animals also have a more robust preterminal gasp. We investigated the relationship between gasping and cardiac function in immature and maturing rats exposed to anoxia. Immature postnatal day 7 (PND7) rats (n13) and maturing PND17 rats (n13) were exposed to 100% nitrogen (anoxia) for 10 min. Echocardiography was used to calculate cardiac contractility (CC) by left ventricular shortening fraction and cardiac output (CO) from Doppler velocity recordings of pulmonary artery blood flow. In a separate group of PND7 rats, CC and CO were recorded after the paralytic agent pancuronium was used to prevent gasping. Anoxia decreased CC and CO in PND7 and PND17 rats, followed by a partial and transient recovery. Gasping preceded recovery of CO and was required to sustain CO. Gasping in PND7 rats lasted longer (541 s versus351 s, p< 0.01) and resulted in a greater recovery of CC and CO. Anoxia-induced gasping and the associated recovery of cardiac function were abolished by paralysis. Thus, anoxia-induced gasping transiently improves cardiac function, and more robust gasping in immature rats is associated with increased cardiac anoxic tolerance.

Newborn animals are more resistant to anoxia than older animals, partly due to an increased tolerance of the immature heart to anoxia. Newborn animals also have a more robust preterminal gasp. We investigated the relationship between gasping and cardiac function in immature and maturing rats exposed to anoxia. Immature postnatal day 7 (PND7) rats (n = 13) and maturing PND17 rats (n = 13) were exposed to 100% nitrogen (anoxia) for 10 min. Echocardiography was used to calculate cardiac contractility (CC) by left ventricular shortening fraction and cardiac output (CO) from Doppler velocity recordings of pulmonary artery blood flow. In a separate group of PND7 rats, CC and CO were recorded after the paralytic agent pancuronium was used to prevent gasping. Anoxia decreased CC and CO in PND7 and PND17 rats, followed by a partial and transient recovery. Gasping preceded recovery of CO and was required to sustain CO. Gasping in PND7 rats lasted longer (541 s versus 351 s, p < 0.01) and resulted in a greater recovery of CC and CO. Anoxia-induced gasping and the associated recovery of cardiac function were abolished by paralysis. Thus, anoxia-induced gasping transiently improves cardiac function, and more robust gasping in immature rats is associated with increased cardiac anoxic tolerance.

Using the whole-cell voltage clamp technique, we investigated the effects of thiopental on membrane currents in H9c2 cells, a cell line derived from embryonic rat heart. Thiopental blocked a rapidly activating, very slowly-inactivating ultra-rapid type IKur-like outward K+current in a concentration-dependent manner. The half-maximal concentration (IC50) of thiopental was 97 µM with a Hill coefficient of 1.2. The thiopental-sensitive current was also blocked by high concentrations of nifedipine (IC50= 9.1 µM) and 100 µM chromanol 293B, a blocker of slowly activating delayed rectifier K+current (IKs), but was insensitive to E-4031, an inhibitor of rapidly activating delayed rectifier K+current (IKr). TEA (tetraethylammonium) at 5 mM and 4-AP (4-aminopiridine) at 1 mM reduced the K+current to 30.8 ± 12.2% and 20.5 ± 6.5% of the control, respectively. Using RT-PCR, we detected mRNAs of Kv2.1, Kv3.4, Kv4.1, and Kv4.3 in H9c2 cells. Among those, Kv2.1 and Kv3.4 have IKur-type kinetics and are therefore candidates for thiopental-sensitive K+channels in H9c2 cells. This is the first report showing that thiopental inhibits IKur. This effect of thiopental may be involved in its reported prolongation of cardiac action potentials.

Left ventricular noncompaction (LVNC) is a recently defined cardiomyopathy characterized by a pattern of prominent trabecular meshwork and deep intertrabecular recesses. LVNC is rarely described in fetal life, and a small number of cases have been reported. We report the first fetal case, to our knowledge, of LVNC associated with a novel mutation in the MYH7gene (c.1625A>C; p.Lys542Thr). This patient showed cardiomegaly on prenatal ultrasonographic examinations, with features indicating noncompaction of the myocardium apparent in the second trimester. This case highlights the importance of prenatal ultrasonography for the diagnosis of LVNC and suggests that abnormal myocardial development underlies the pathogenesis of LVNC.

AbstractClassical citrullinemia generally involves hyperammonemic coma in the first few days of life and leads to neurological sequelae in survivors. We report a case of an elder sister who fell into a hyperammonemic coma on the fifth day after birth. She was successfully treated with intravenous benzoate and hemodialysis, and was subsequently diagnosed with citrullinemia on the basis of biochemical analysis. Two years later, a younger sister was born without prenatal diagnosis. We monitored plasma ammonia and citrulline levels after birth, and again diagnosed her with CTLN1 on the basis of biochemical and DNA analyses. There have been few reports of the prospective treatment of citrullinemia; however, our experience indicates the need for the prospective management and the rapid reduction of ammonia levels to avoid neonatal hyperammonemic coma and subsequent sequelae.