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

Lactacidemia in intrauterine growth restricted (IUGR) pregnancies : relationship to clinical severity, oxygenation and placental weight

The aim of the study was to evaluate the impact of clinical severity and placental weight upon fetal lactacidemia in intrauterine growth restricted (IUGR) pregnancies. Seventy pregnancies complicated by IUGR were compared with 70 normal (appropriate for gestational age, AGA) pregnancies at the time of elective cesarean section. IUGR pregnancies were divided according to clinical severity in three groups: Group 1 had normal fetal heart rate (FHR) and normal pulsatility index of the umbilical artery (PI); Group 2 had normal FHR and abnormal PI; and Group 3 had abnormal FHR and PI. No cases with severe lactacidemia had placental weights >or=250 g. Forty-four fetuses had placental weight or=250 g exhibited an F/P ratio significantly lower than that in AGA fetuses suggesting that IUGR may be due to a reduction of placental function per gram of tissue

Fetal and maternal non-glucose carbohydrates and polyols concentrations in normal human pregnancies at term

The objective of the present investigation was to determine fetal and maternal plasma concentrations of nonglucose carbohydrates and polyols in normal human pregnancies at term. Uncomplicated human pregnancies (n = 50) were studied at > or =37 wk gestation. Blood samples were obtained from umbilical artery, umbilical vein, and maternal peripheral blood at the time of elective cesarean section. Plasma concentrations of inositol, glycerol, erythritol, sorbitol, and mannose were determined by HPLC analysis. Differences between umbilical venous, umbilical arterial, and maternal concentration were tested by the two-tailed t test for paired samples. Correlations between umbilical and maternal concentration and between umbilical venoarterial concentration difference and umbilical arterial concentration were assessed by Pearson's correlation and multiple regression analysis. All newborns were appropriate for gestational age, and oxygenation and acid-base balance were within the normal range for all fetuses studied. For most of the polyols (inositol, sorbitol, and erythritol), the fetal concentration was significantly higher than the maternal concentration. The umbilical venoarterial concentration difference for inositol was -10.5 +/- 3.6 microM, for glycerol was 10 +/- 1.7 microM, for sorbitol was 3.8 +/- 0.5 microM (p < 0.001), and for mannose was 7.6 +/- 0.7 microM. There was a significant correlation between maternal concentration and umbilical venous concentration of mannose (UV(MAN) = 15.38 + 0.69 M(MAN); R(2) = 0.46; p < 0.001). These results indicate that in normal human pregnancies at term, inositol is produced by the fetus, sorbitol is produced by the placenta, and there is a significant umbilical uptake of mannose from the maternal circulation

Transplacental Supply of Mannose and Inositol in Uncomplicated Pregnancies Using Stable Isotopes

OBJECTIVE: The aim of this study was to determine relative contributions of transplacental flux vs. fetal production for inositol and mannose in normal term pregnancies. STUDY DESIGN: Seven term uncomplicated pregnancies undergoing cesarean section were infused with (13)C- and (2)H-labeled isotopes of glucose, inositol, and mannose until a steady state was achieved. Maternal and fetal concentrations of labeled and unlabeled glucose, mannose, and inositol were measured using gas chromatography/mass spectroscopy. The fetomaternal molar percentage excess ratio was calculated for each glucose, mannose, and inositol. RESULTS: The fetomaternal molar percentage excess ratio of mannose in the fetal artery (F(artery)/M) was 0.99 [97.5% confidence interval (CI), 0.91-1.07] and in the fetal vein (F(vein)/M), 1.02 (97.5% CI, 0.95-1.10). Both were not significantly different from 1.0, consistent with transplacental supply. The fetomaternal ratios for glucose were similar to mannose (fetal artery, 0.95; 97.5% CI, 0.84-1.15; and fetal vein, 0.96; 97.5% CI, 0.85-1.07). The fetomaternal ratio for inositol was significantly less than 1.0 (fetal artery, 0.08; 97.5% CI, 0.05-0.12; fetal vein, 0.12; 97.5% CI, 0.06-0.18), indicating little transplacental flux and significant fetal production. CONCLUSION: In normal term pregnancies, fetal mannose and glucose concentrations are dependent upon maternal transplacental supply. Fetal inositol is not dependent upon transplacental supply

Magnetic Fields, Relativistic Particles, and Shock Waves in Cluster Outskirts

It is only now, with low-frequency radio telescopes, long exposures with high-resolution X-ray satellites and gamma-ray telescopes, that we are beginning to learn about the physics in the periphery of galaxy clusters. In the coming years, Sunyaev-Zeldovich telescopes are going to deliver further great insights into the plasma physics of these special regions in the Universe. The last years have already shown tremendous progress with detections of shocks, estimates of magnetic field strengths and constraints on the particle acceleration efficiency. X-ray observations have revealed shock fronts in cluster outskirts which have allowed inferences about the microphysical structure of shocks fronts in such extreme environments. The best indications for magnetic fields and relativistic particles in cluster outskirts come from observations of so-called radio relics, which are megaparsec-sized regions of radio emission from the edges of galaxy clusters. As these are difficult to detect due to their low surface brightness, only few of these objects are known. But they have provided unprecedented evidence for the acceleration of relativistic particles at shock fronts and the existence of muG strength fields as far out as the virial radius of clusters. In this review we summarise the observational and theoretical state of our knowledge of magnetic fields, relativistic particles and shocks in cluster outskirts.Comment: 34 pages, to be published in Space Science Review

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented