Glutamate is produced by the fetal liver and taken up by the placenta. To explore the functional meaning of this exchange, the disposal rate (DR), clearance, conversion to glutamine, and decarboxylation rate of fetal plasma glutamate were studied at 129 +/- 2 days of gestation in seven fetal lambs infused via a systemic vein with L-[2,3,3,4,4-2H5]glutamate and L-[1-14C]glutamate. In two experiments, L-[1-13C]glutamate was also infused. The mean glutamate DR and clearance were 11.9 +/- 1.3 mumol.min-1.kg-1 and 200 +/- 8 ml.min-1.kg-1, respectively. The placenta extracted 88.5 +/- 0.8% of the tracer glutamate carried by the umbilical circulation and contributed to 61.3 +/- 3.2% of the glutamate DR. Most of the 14C infused as L-[1-14C]glutamate was converted to 14CO2: 37 +/- 4% by the fetus and 41 +/- 6% by the placenta. Of the labeled glutamate taken up by the placenta, 6.2 +/- 1.5% was returned to the fetus as glutamine. The glutamine-to-glutamate enrichment ratio in fetal arterial plasma was 0.066 +/- 0.008. We conclude that fetal plasma glutamate has an exceptionally high clearance because the flux of glutamate into the placenta is virtually equal to umbilical glutamate delivery rate. The main pathway of fetal plasma glutamate disposal is oxidation by placental and fetal tissues. Placental conversion of glutamate to fetal glutamine is a relatively small component of the placental metabolism of fetal glutamate.

This data supports the hypothesis that APLD may be an effective adjunctive therapy against ATC. The demonstrated molecular impact against angiogenic related genes specifically supports future strategies combining APLD with VEGF interacting agents.

NRAS correlates with Apgar status assessment, and identifies newborns who die or may require further care better than the Apgar score.

No abstract

Non-invasive ventilation is increasingly used for respiratory support in preterm infants, and is associated with a lower risk of chronic lung disease. However, this mode is often not successful in the extremely preterm infant in part due to their markedly increased chest wall compliance that does not provide enough structure against which the forces of inhalation can generate sufficient pressure. To address the continued challenge of studying treatments in this fragile population, we developed a nonlinear lumped-parameter respiratory system mechanics model of the extremely preterm infant that incorporates nonlinear lung and chest wall compliances and lung volume parameters tuned to this population. In particular we developed a novel empirical representation of progressive volume loss based on compensatory alveolar pressure increase resulting from collapsed alveoli. The model demonstrates increased rate of volume loss related to high chest wall compliance, and simulates laryngeal braking for elevation of end-expiratory lung volume and constant positive airway pressure (CPAP). The model predicts that low chest wall compliance (chest stiffening) in addition to laryngeal braking and CPAP enhance breathing and delay lung volume loss. These results motivate future data collection strategies and investigation into treatments for chest wall stiffening.