7 research outputs found
Induction of glutamate dehydrogenase in the ovine fetal liver by dexamethasone infusion during late gestation
Glucocorticoids near term are known to upregulate many important enzyme
systems prior to birth. Glutamate dehydrogenase (GDH) is a mitochondrial
enzyme that catalyzes both the reversible conversion of ammonium nitrogen
into organic nitrogen (glutamate production) and the oxidative deamination
of glutamate resulting in 2-oxoglutarate. The activity of this enzyme is
considered to be of major importance in the development of catabolic
conditions leading to gluconeogenesis prior to birth. Ovine hepatic GDH
mRNA expression and activity were determined in near-term (130 days of
gestation, term 147 +/- 4 days) control and acutely dexamethasone-treated
(0.07 mg(-1) hr(-1) for 26 hr) fetuses. Dexamethasone infusion had no
effect on placental or fetal liver weights. Dexamethasone infusion for 26
hr significantly increased hepatic GDH mRNA expression. This increased GDH
mRNA expression was accompanied by an increase in hepatic mitochondrial
GDH activity, from 30.0 +/- 7.4 to 58.2 +/- 8.1 U GDH/U CS (citrate
synthase), and there was a significant correlation between GDH mRNA
expression and GDH activity. The generated ovine GDH sequence displayed
significant similarity with published human, rat, and murine GDH sequence.
These data are consistent with the in vivo studies that have shown a
redirection of glutamine carbon away from net hepatic glutamate release
and into the citric acid cycle through the forward reaction catalyzed by
GDH, i.e., glutamate to oxoglutarate
Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange
Intravenous infusion of dexamethasone (Dex) in the fetal lamb causes a
two- to threefold increase in plasma glutamine and other glucogenic amino
acids and a decrease of plasma glutamate to approximately one-third of
normal. To explore the underlying mechanisms, hepatic amino acid uptake
and conversion of L-[1-(13)C]glutamine to L-[1-(13)C]glutamate and
(13)CO(2) were measured in six sheep fetuses before and in the last 2 h of
a 26-h Dex infusion. Dex decreased hepatic glutamine and alanine uptakes
(P < 0.01) and hepatic glutamate output (P < 0.001). Hepatic outputs of
the glutamate (R(Glu,Gln)) and CO(2) formed from plasma glutamine
decreased to 21 (P < 0.001) and 53% (P = 0.009) of control, respectively.
R(Glu,Gln), expressed as a fraction of both outputs, decreased (P < 0.001)
from 0.36 +/- 0.02 to 0.18 +/- 0.04. Hepatic glucose output remained
virtually zero throughout the experiment. We conclude that Dex decreases
fetal hepatic glutamate output by increasing the routing of glutamate
carbon into the citric acid cycle and by decreasing the hepatic uptake of
glucogenic amino acids
Relationship of fetal alanine uptake and placental alanine metabolism to maternal plasma alanine concentration
Uterine and umbilical uptakes of alanine (Ala) were measured in 10 ewes
before (control) and during intravenous infusion of Ala, which increased
maternal arterial Ala concentration from 115 +/- 14 to 629 +/- 78 microM
(P < 0.001). In 8 of these ewes, placental Ala fluxes were traced by
constant intravenous infusion of L-[3,3,3-2H3]Ala in the mother and
L-[1-13C]Ala in the fetus. Rates are reported as micromoles per minute per
kilogram fetus. Ala infusion increased uterine uptake (2.5 +/- 0.6 to 15.6
+/- 3.1, P < 0.001), umbilical uptake (3.1 +/- 0.5 to 6.9 +/- 0.8, P <
0.001), and net uteroplacental utilization (-0.7 +/- 0.8 to 8.6 +/- 2.7, P
< 0.01) of Ala. Control Ala flux to fetus from mother (Rf,m) was much less
than the Ala flux to fetus from placenta (Rf,p) (0.17 +/- 0.04 vs. 5. 0
+/- 0.6). Two additional studies utilizing L-[U-13C]Ala as the maternal
tracer confirmed the small relative contribution of Rf,m to Rf,p. During
maternal Ala infusion, Rf,m increased significantly (P < 0.02) but
remained a small fraction of Rf,p (0.71 +/- 0.2 vs. 7.3 +/- 1.3). We
conclude that maternal Ala entering the placenta is metabolized and
exchanged for placental Ala, so that most of the Ala delivered to the
fetus is produced within the placenta. An increase in maternal Ala
concentration increases placental Ala utilization and the fetal uptake of
both maternal and placental Ala
Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR).
Item does not contain fulltextPlacental development requires adequate and organized interaction of vascular growth factors and their receptors, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Both VEGF and PlGF, acting through the tyrosine kinase receptors VEGFR-1 and VEGFR-2, have been implicated in playing a role in ovine placental vascular development. The present studies describe the placental expression of components of the VEGF family at two maturational time points (55 and 90 days post coitus, dpc) in a hyperthermic-induced ovine model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Both caruncular and cotyledonary VEGF and PlGF mRNA concentration increased with gestational age (P< 0.05), whereas only cotyledonary VEGF and PlGF protein concentration increased over gestation (P< 0.002). At 55 dpc, VEGF mRNA concentration was elevated in hyperthermic (HT) ewes, compared to control thermoneutral (TN) animals (TN; 0.52+/-0.08 vs HT; 1.27+/-0.17 VEGF/GAPDH, P< 0.001). At 90 dpc, expression of PlGF and VEGF mRNA was not altered by the HT treatment. Both TN cotyledonary VEGFR-1 and VEGFR-2 mRNA expression levels rose significantly over the period studied (P< 0.05 and P< 0.01 respectively). Receptor mRNA concentration in HT cotyledonary tissue was significantly reduced at 90 dpc (VEGFR-1; TN 0.21+/-0.02 vs HT 0.11+/-0.01 VEGFR-1/actin, P< 0.05, VEGFR-2; TN 0.18+/-0.05 vs HT 0.07+/-0.01 VEGFR-2/actin, P< 0.01). Soluble VEGFR-1 (sVEGFR-1) mRNA was not detected in these tissues. These alterations in growth factor and growth factor receptor mRNA expression, as a result of environmental heat stress early in placental development, could impair normal placental vascular development. Furthermore, alterations in VEGF, VEGFR-1 and VEGFR-2 mRNA expression, during the period of maximal placental growth, may contribute to the development of placental insufficiency, and ultimately intrauterine growth restriction
Fetal hypertension and abnormal Doppler velocimetry in an ovine model of intrauterine growth restriction
Our objective was to test the hypothesis that systemic blood pressure (BP) is increased above normal in intrauterine growth restricted (IUGR) fetal lambs with elevated umbilical artery (UmA) Doppler indices. Five pregnant ewes were exposed to hyperthermic conditions for 80 days beginning at 40 days' gestation (dGA) to induce IUGR. They were then placed in ambient conditions with 6 additional ewes that served as controls. Doppler indices were calculated from UmA Doppler flow velocity waveforms. At 128 dGA, fetal catheters were placed for measurement of umbilical blood flow (UBF) by an ethyl alcohol steady-state diffusion technique and for aortic BP measurements. At 132 dGA, fetal mean systemic BP and blood flow were determined. At necropsy the placental and fetal weights were recorded. UBF was normalized for fetal weight. Linear regression, F tests and t tests were performed as appropriate. P <. 05 was considered significant. Compared with control pregnancies, the IUGR pregnancies showed: (1) reduced fetal and placental weights, (2) elevated systemic BP, (3) reduced UBF, (4) elevated UmA and aortic Doppler velocimetry indices, (5) increased resistance per 100 g placenta, and (6) decreased UmA oxygenation and increased lactic academia. The UmA Doppler index of resistance (systolic/diastolic ratio) correlated strongly with calculated resistance (R 2 = 0.7). Doppler indices also correlated with systemic BP (R 2 = 0.5). Ovine IUGR fetuses with high UmA Doppler indices have elevated systemic BPs. UmA Doppler indices of resistance correlate well with (1) fetal systemic BPs and (2) resistance as calculated by pressure/flow. This whole animal study shows that IUGR fetuses are hypertensive and that increased UmA Doppler resistance indices are consistent with a fetal-placental hypertensive state
How users interact with a 3D geo-browser under time pressure
Interactive 3D geo-browsers, also known as globe viewers, are popular, because they are easy and fun to use. However, it is still an open question whether highly interactive, 3D geographic data browsing, and visualization displays support effective and efficient spatio-temporal decision making. Moreover, little is known about the role of time constraints for spatio-temporal decision-making in an interactive, 3D context. In this article, we present an empirical approach to assess the effect of decision-time constraints on the quality of spatio-temporal decision-making when using 3D geo-browsers, such as GoogleEarth, in 3D task contexts of varying complexity. Our experimental results suggest that while, overall, people interact more with interactive geo-browsers when not under time pressure, this does not mean that they are also more accurate or more confident in their decisions when solving typical 3D cartometric tasks. Surprisingly, we also find that 2D interaction capabilities (i.e., zooming and panning) are more frequently used for 3D tasks than 3D interaction tools (i.e., rotating and tilting), regardless of time pressure. Finally, we find that background and training of tested users do not seem to influence 3D task performance. In summary, our study does not provide any evidence for the added value of using interactive 3D globe viewers when needing to solve 3D cartometric tasks with or without time pressure