Skeletal muscle protein accretion rates and hindlimb growth are reduced in late gestation intrauterine growth-restricted fetal sheep.

Key Points: Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes. We demonstrate slower hindlimb linear growth and muscle protein synthesis rates that match the reduced hindlimb blood flow and oxygen consumption rates in IUGR fetal sheep. These adaptations resulted in hindlimb blood flow rates in IUGR that were similar to control fetuses on a weight-specific basis.

Review of studies in human pregnancy of uterine and umbilical blood flows.

Uterine and umbilical blood flow measurements are reviewed in terms of studies carried out in uncomplicated human pregnancies. The review includes the perspective of how those estimates of flow fit with current knowledge of human fetal O2 consumption and uterine O2 and glucose consumption. From the consideration of both the O2 data and the flow measurements, we conclude that the best estimates for mean umbilical blood flow at term range between 120 and 145 ml•min-1•(kg fetus)-1.

Umbilical uptakes and transplacental concentration ratios of amino acids in severe fetal growth restriction.

Background: This study examines the relationship between placental amino acid (AA) transport and fetal AA demand in an ovine fetal growth restriction (FGR) model in which placental underdevelopment induces fetal hypoxemia and hypoglycemia.

Methods: Umbilical uptakes of AA, oxygen, glucose, and lactate were measured near term in eight experimental ewes (FGR group) and in eight controls (C group).

Results: The FGR group demonstrated significantly reduced umbilical uptakes of oxygen, glucose, lactate, and 11 AAs per kg fetus.

Fetal oxygenation and maternal ventilation.

In the past 20 years, measurements of umbilical blood flow and umbilical venous PO2, oxygen saturation, pH, and oxygen capacity have provided reliable information about the state of oxygenation of normal and growth restricted human fetuses. However, no comparable information is available about the uterine circulation. Therefore, understanding of oxygen transport across the human placenta and the effect of maternal ventilation on fetal oxygenation is tentative, and currently based on a model that is derived from evidence in another species.

In vitro comparison of the flexibility of different splint systems used in dental traumatology.

Aim: The aim of the study was to evaluate the flexibility of five different splint systems [polyethylene fibre-reinforced splint (Ribbond THM, Ribbond Inc., Seattle, WA, USA), resin splint (RS), wire-composite splint (WCS), button-bracket splint (BS) and titanium trauma splint (TTS)] commonly used in clinical practice for the treatment of dental traumatic injuries involving the periodontal supporting tissues.

Materials And Methods: For the experimental study, a resin cast of the upper arch was manufactured, where teeth 11, 12 and 21 (used for the stress analysis) were inserted in a non-rigid fashion so as to allow for replacement, whereas the other teeth were permanently fixed to the corresponding sockets.

Development and mechanisms of fetal hypoxia in severe fetal growth restriction.

Severe fetal growth restriction (FGR) is often associated with hypoxia. We studied FGR hypoxia in an experimental model which is produced by exposing pregnant ewes to a hyperthermic environment. The study utilized simultaneous measurements of several relevant factors, e.

Placental uptake and transport of ACP, a neutral nonmetabolizable amino acid, in an ovine model of fetal growth restriction.

Reductions in fetal plasma concentrations of certain amino acids and reduced amino acid transport in vesicle studies suggest impaired placental amino acid transport in human fetal growth restriction (FGR). In the present study, we tested the hypothesis of an impairment in amino acid transport in the ovine model of hyperthermia-induced FGR by determining transplacental and placental retention and total placental clearance of a branched-chain amino acid (BCAA) analog, the nonmetabolizable neutral amino acid aminocyclopentane-1-carboxylic acid (ACP), in singleton control (C) and FGR pregnancies at 135 days gestation age (dGA; term 147 dGA). At study, based on the severity of the placental dysfunction, FGR fetuses were allocated to severe (sFGR, n = 6) and moderate FGR (mFGR, n = 4) groups.

The effect of an elevated maternal lysine concentration on placental lysine transport in pregnant sheep.

Objectives: In a previous study, the coinfusion into the maternal circulation of lysine and several other amino acids failed to increase significantly lysine umbilical uptake. The purpose of this study was to determine whether umbilical lysine uptake can be increased by infusing a lysine solution that does not contain any other amino acid.

Study Design: Six late-gestation ewes were studied on 2 consecutive days.

Reciprocal inhibition of umbilical uptake within groups of amino acids.

Eight pregnant sheep were infused with two amino acid mixtures of different composition: essential amino acids only and the essentials plus some of the nonessentials. Uterine and umbilical uptakes of amino acids were measured before and during infusion. For most of the amino acids, the infusion increased both maternal plasma concentration and umbilical uptake.

Umbilical threonine uptake during maternal threonine infusion in sheep.

Objective: The infusion into the maternal circulation of amino acid solutions failed to increase umbilical threonine (THR) uptake above normal even when THR was present in the infusate at a relatively high concentration. The purpose of the present study was to determine whether umbilical THR uptake can be increased by infusing a THR solution that does not contain any other amino acids.

Study Design: Five pregnant sheep (130+/-1.

Fetal hepatic and umbilical uptakes of glucogenic substrates during a glucagon-somatostatin infusion.

To test the hypothesis that fetal hepatic glutamate output diverts the products of hepatic amino acid metabolism from hepatic gluconeogenesis, ovine fetal hepatic and umbilical uptakes of glucose and glucogenic substrates were measured before and during fetal glucagon-somatostatin (GS) infusion and during the combined infusion of GS, alanine, glutamine, and arginine. Before the infusions, hepatic uptake of lactate, alanine, glutamine, arginine, and other substrates was accompanied by hepatic output of pyruvate, aspartate, serine, glutamate, and ornithine. The GS infusion induced hepatic output of 1.

Effects of branched-chain amino acids on placental amino acid transfer and insulin and glucagon release in the ovine fetus.

Objective: Competition for placental amino acid transporters can affect the fetal supply of amino acids. Specifically, the branched-chain amino acids-isoleucine, leucine, and valine-may inhibit the transfer of other amino acids. This study was undertaken to determine the effect of branched-chain amino acids on the umbilical uptake of amino acids.

An in vivo study of ovine placental transport of essential amino acids.

Under normal physiological conditions, essential amino acids (EA) are transported from mother to fetus at different rates. The mechanisms underlying these differences include the expression of several amino acid transport systems in the placenta and the regulation of EA concentrations in maternal and fetal plasma. To study the relation of EA transplacental flux to maternal plasma concentration, isotopes of EA were injected into the circulation of pregnant ewes.

Elizabeth M. Ramsey and the evolution of ideas of uteroplacental blood flow and placental gas exchange.

During the past century a number of investigators have contributed to an understanding of the regulation of uteroplacental blood flow and its influence on placental respiratory gas exchange and fetal oxygenation. Among these, Elizabeth M. Ramsey is noteworthy for her contributions to embryology and placental development.

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.

Contribution of branched-chain amino acids to uteroplacental ammonia production in sheep.

The uteroplacental tissues are a principal site of ammonia production for the conceptus. The goal of this study was to examine the effect of the composition of maternal amino acid (AA) infusate on uteroplacental ammonia production. Seven pregnant ewes (126 +/- 1.

Fetal supply of amino acids and amino nitrogen after maternal infusion of amino acids in pregnant sheep.

Objective: The objective of the study was to determine whether a prolonged maternal infusion of amino acids would increase the umbilical uptake of amino acids and uteroplacental ammonia production.

Study Design: Six pregnant sheep (134.5 2.

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.

Uptake and transport by the ovine placenta of neutral nonmetabolizable amino acids with different transport system affinities.

Placental uptake and transport of three nonmetabolizable amino acids with different reactivities for transport systems were studied in sheep under normal physiologic conditions. Methylaminoisobutyric acid (MeAIB), which has specific affinity for the sodium-dependent A system transporters, demonstrated placental concentrative uptake from the uterine and the umbilical circulations, but virtually no transport from mother to fetus. By contrast, aminoisobutyric acid (AIB) and aminocyclopentane-1-carboxylic acid (ACP), which have affinity for both sodium-dependent and sodium-independent transporters, demonstrated both concentrative uptake and transport from mother to fetus.

Production and utilization of amino acids by ovine placenta in vivo.

Uterine and umbilical uptakes of plasma amino acids were measured simultaneously in eighteen singleton pregnant ewes at 130 +/- 1 days gestation for the purpose of establishing which amino acids are produced or used by the uteroplacenta under normal physiological conditions and at what rates. The branched-chain amino acids (BCAA) had uterine uptakes significantly greater than umbilical uptakes. Net uteroplacental BCAA utilization was 8.

Placental transport of threonine and its utilization in the normal and growth-restricted fetus.

Placental transport and fetoplacental utilization of threonine (Thr) were compared at 130 +/- 1 days gestational age between seven control ewes (C) and six ewes in which intrauterine growth restriction (IUGR) had been induced by exposure to high ambient temperature from 33 +/- 1 to 112 +/- 2 days of gestation. The fluxes were measured using simultaneous intravenous infusions of L-[1-13C]Thr into the mother and L-[U-14C]Thr into the fetus. The IUGR group had less fetal weight (1.

Metabolic alterations in the fetal hepatic and umbilical circulations during glucocorticoid-induced parturition in sheep.

Fetal hepatic amino acid metabolism has unique features in comparison to postnatal life. Thus, it seemed likely that this metabolism might be changed by the endocrine changes which precede birth. To explore the changes in placental and fetal carbohydrate and amino acid metabolism that occur during parturition, labor was induced in six ewes at 131 +/- 1 d gestation with a fetal infusion of dexamethasone.