Search PubMed⌕ Search

Biomedical subjects

W W Hay

Publications and source records attributed to W W Hay.

At least 37 records · Page 2Linked to original sources
PubMed1999

Time-dependent and tissue-specific effects of circulating glucose on fetal ovine glucose transporters.

To determine the cellular adaptations to fetal hyperglycemia and hypoglycemia, we examined the time-dependent effects on basal (GLUT-1 and GLUT-3) and insulin-responsive (GLUT-4) glucose transporter proteins by quantitative Western blot analysis in fetal ovine insulin-insensitive (brain and liver) and insulin-sensitive (myocardium, skeletal muscle, and adipose) tissues. Maternal glucose infusions causing fetal hyperglycemia resulted in a transient 30% increase in brain GLUT-1 but not GLUT-3 levels and a decline in liver and adipose GLUT-1 and myocardial and skeletal muscle GLUT-1 and GLUT-4 levels compared with gestational age-matched controls. Maternal insulin infusions leading to fetal hypoglycemia caused a decline in brain GLUT-3, an increase in brain GLUT-1, and a subsequent decline in liver GLUT-1, with no significant change in insulin-sensitive myocardium, skeletal muscle, and adipose tissue GLUT-1 or GLUT-4 concentrations, compared with gestational age-matched sham controls. We conclude that fetal glucose transporters are subject to a time-dependent and tissue- and isoform-specific differential regulation in response to altered circulating glucose and/or insulin concentrations. These cellular adaptations in GLUT-1 (and GLUT-3) are geared toward protecting the conceptus from perturbations in substrate availability, and the adaptations in GLUT-4 are geared toward development of fetal insulin resistance.

Animals↗
PubMed1999

Effect of glucose supply on ovine uteroplacental glucose metabolism.

To test the hypothesis that glucose supply to the uteroplacenta (UP) regulates UP glucose metabolism into oxidative and nonoxidative pathways, we studied eight late-gestation pregnant sheep at low (LG) and high (HG) maternal glucose concentrations (G(M)), using Fick principle and tracer glucose methodology. UP glucose consumption (UPGC) correlated directly with G(M) (r = 0.75, P = 0.0006), and UP glucose decarboxylation (r = 0.80, P = 0.0001), and lactate production (r = 0.90, P = 0.0001) rates were directly correlated with UPGC. The combined fractional production rate for lactate, fructose, and CO(2) from UPGC was the same in LG and HG periods. The fraction of UP oxygen consumption used for glucose oxidation increased by about 50% from LG to HG conditions; however, there was no change in UP oxygen consumption. Nearly half of UPGC was not accounted for by lactate, fructose, and CO(2) production, and about two-thirds of UP oxygen consumption was not accounted for by immediate oxidation of glucose carbon just taken up by the UP. These results indicate that glucose supply directly regulates UP glucose oxidative metabolism and that there is a reciprocal relationship between UP glucose oxidation and the oxidation of other substrates.

Animals↗
PubMed1999

Determinants of energy expenditure in ventilated preterm infants.

The purpose of this study was to determine oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (EE) in a group of preterm ventilated infants during the first 3 weeks of life, and to determine the major factors that influence EE. Thirty-eight indirect calorimetry studies were performed in 18 ventilated infants with mean gestational age of 27.9 +/- 0.6 (SEM) weeks. The relationship of demographic factors, nutrient intake, and severity of illness assessments of EE were determined by regression analysis. Repeated measure analysis was performed for the effect of multiple studies in the same patient. Although VO2, VCO2, and EE all tended to increase over the first 3 weeks of life, there was a wide range of values. EE was best predicted by nonprotein calorie intake and postnatal age, while there was no correlation with birthweight, weight at the time of study, gestational age, protein intake, or severity of illness. Multiple regression analyses demonstrated a strong interaction between PNA and EI. In this population EE is best predicted by PNA and EI. The interactive effect between PNA and EI on EE is probably explained by the clinical practice of daily increments in substrate intake in these patients.

Aging↗
PubMed1999

Placental transport of nutrients and its implications for fetal growth.

Placental growth during early and mid-pregnancy has a powerful, constraining influence on fetal growth during late pregnancy. Studies involving surgical and environmental reduction of placental size in sheep have shown an associated reduction in capacity to transport oxygen, glucose and amino acids. Oxygen transport is limited by placental blood flow but transport of glucose and amino acids is determined by the abundance and activity of specific transport proteins. Glucose transporters include the GLUT1 and GLUT3 isoforms previously identified in brain and other tissues; systems for active transport of amino acids have been inferred but not characterized. Placental metabolism of glucose and amino acids has major effects both on the quantity of carbon and nitrogen delivered to the fetus, and on the composition of substrates involved. For example, the uteroplacental tissues consume more than 60% of uterine glucose uptake during late pregnancy, and the placenta substantially modifies the pattern of amino acids delivered to fetal blood. The placenta also participates in the array of metabolic adaptations of maternal and conceptus tissues to altered maternal nutrient supply. Placental capacity for glucose transport in moderately undernourished ewes is upregulated, partly by increased expression of the GLUT3 transport protein. During more severe glucose deprivation, placental transfer and fetal uptake of glucose are constrained in proportion with maternal supply, leading to fetal growth retardation.

Amino Acids↗
PubMed1998

Prediction of arterial partial pressure of oxygen with pulse oxygen saturation measurements.

OBJECTIVES: We studied 22 neonates with gestational ages from 26 to 40 weeks to determine how accurately pulse oxygen saturation (SpO2) could predict arterial partial pressure of oxygen (PaO2) and how much time and effort would be required to achieve and maintain a desired SpO2 value. STUDY DESIGN: SpO2 was maintained at 90%, 92%, 94%, 96%, and 98% by adjustment of FiO2. PaO2 was correlated with SpO2 by nonlinear mixed effects regression analysis. RESULTS: PaO2(y) correlated positively with SpO2(x): y = (0.03). e0.08(x). Variation of PaO2 increased from a range of +/- 10 Torr at SpO2 = 90% to +/- 28 Torr at SpO2 = 98%, principally as a result of decreasing hemoglobin-oxygen affinity, with no effect of advancing gestational age, subject temperature, pH, PaCO2. Considerable time (18 +/- 14 SD minutes) and effort (5 +/- 3 SD FiO2 adjustments/min were required to achieve and maintain a desired SpO2. CONCLUSIONS: PaO2 varied broadly with SpO2 in a clinically acceptable range of SpO2 (90% to 98%), and the variability increased at higher SpO2 values. Considerable time and effort were required to achieve and maintain desired SpO2 values.

Gestational Age↗
PubMed1998

Protein balance in the first week of life in ventilated neonates receiving parenteral nutrition.

BACKGROUND: Protein intake is frequently delayed in ill neonates because of concerns about their ability to metabolize substrates. OBJECTIVE: We aimed to determine the factors affecting protein balance in ventilated, parenterally fed newborns during the first week of life. DESIGN: Leucine kinetic studies were performed in 19 neonates by using the [1-(13)C]leucine tracer technique after 24 h of a stable total parenteral nutrition (TPN) regimen. TPN intakes were prescribed by rotating attending physicians, enabling assessment of protein metabolism over a range of clinically used nutrient intakes. RESULTS: Mean (+/-SD) birth weight was 1.497 +/- 0.779 kg, gestational age at birth was 30.3 +/- 4.0 wk, and age at study was 3.9 +/- 1.4 d. Amino acid intakes (AAIs) ranged from 0.0 to 2.9 g x kg(-1) x d(-1). Based on leucine kinetic data, protein balance was calculated as the difference between protein synthesis and catabolism. By multiple regression analysis, AAI was the only predictor associated independently with protein balance (P < 0.01); energy intake, lipid intake, glucose intake, birth weight, and gestational age were not. Both leucine oxidation and nonoxidative leucine disposal rates were significantly correlated with leucine intake (P < 0.0005 and P < 0.01, respectively). Of the 12 infants with AAIs > 1 g x kg(-1) x d(-1), only 1 infant was significantly catabolic (protein balance <-1 g x kg(-1) x d(-1)). There was no evidence of protein intolerance as determined by elevated creatinine (69 +/- 31 micromol/L), plasma urea nitrogen (6.7 +/- 2.53 mmol/L), or metabolic acidosis (pH: 7.36 +/- 0.05). CONCLUSIONS: Ill neonates can achieve a positive protein balance in the first days of life without laboratory evidence of protein toxicity.

Amino Acids↗
PubMed1998

Time-dependent physiological regulation of rodent and ovine placental glucose transporter (GLUT-1) protein.

To examine the in vivo and in vitro time-dependent effects of glucose on placental glucose transporter (GLUT-1) protein levels, we employed Western blot analysis using placenta from the short-term streptozotocin-induced diabetic pregnancy (STZ-D), uterine artery ligation-intrauterine growth restriction (IUGR) rat models, pregnant sheep exposed to chronic maternal glucose and insulin infusions, and the HRP.1 rat trophoblastic cell line exposed to differing concentrations of glucose. In the rat, 6 days of STZ-D with maternal and fetal hyperglycemia caused no substantive change, whereas 72 h of IUGR with fetal hypoglycemia and ischemic hypoxia resulted in a 50% decline in placental GLUT-1 levels (P < 0.05). In late-gestation ewes, maternal and fetal hyperglycemia caused an initial threefold increase at 48 h (P < 0.05), with a persistent decline between 10 to 21 days, whereas maternal and fetal hypoglycemia led to a 30-50% decline in placental GLUT-1 levels (P < 0.05). Studies in vitro demonstrated no effect of 0 mM, whereas 100 mM glucose caused a 60% decline (P < 0.05; 48 h) in HRP.1 GLUT-1 levels compared with 5 mM of glucose. The added effect of hypoxia on 0 and 100 mM glucose concentrations appeared to increase GLUT-1 concentrations compared with normoxic cells (P < 0.05; 100 mM at 18 h). We conclude that abnormal glucose concentrations alter rodent and ovine placental GLUT-1 levels in a time- and concentration-dependent manner; hypoxia may upregulate this effect. The changes in placental GLUT-1 concentrations may contribute toward the process of altered maternoplacentofetal transport of glucose, thereby regulating placental and fetal growth.

Animals↗
PubMed1998

Direct measurement of the energy expenditure of physical activity in preterm infants.

The energy cost of physical activity (EEA) has been estimated to account for 5-17% of total energy expenditure (TEE) in neonates. To directly measure EEA, a force plate was developed and validated to measure work outputs ranging from 0.3 to 40 kcal . kg-1 . day-1. By use of this force plate plus indirect calorimetry, TEE and EEA were measured and correlated with five activity states in 24 infants with gestational age of 31.6 +/- 0.5 (SE) wk and postnatal age of 24.8 +/- 3.7 days. TEE and EEA were 69.2 +/- 1.5 and 2.4 +/- 0.2 kcal . kg-1 . day-1, respectively. EEA per state was 0.5 +/- 0.0 (quiet sleep), 2.4 +/- 0.2 (active sleep), 2.8 +/- 0.4 (quiet awake), 7.5 +/- 0.8 (active awake), and 15.1 +/- 2.3 (crying) kcal . kg-1 . day-1. This provides the first direct measurement of the contribution of physical activity to TEE in preterm infants and will enable measurement of caloric expenditure from muscle activity in various disease conditions and development of nursing strategies to minimize unnecessary energy losses.

Algorithms↗
PubMed1998

Maturation of glucose-stimulated insulin secretion in fetal sheep.

To determine the gestational maturation of fetal insulin response to glucose and arginine and the effects of sustained hyperglycemia on these processes, we measured insulin secretion in different groups of fetal sheep at 75, 100, 122, and 137 days of gestation (50, 67, 81, and 91% of term gestation, respectively). The basal glucose concentration decreased progressively from 1.36 +/- 0.16 mM at 75 days to 1.00 +/- 0.07 mM at 137 days (p < 0.05). The fetal plasma insulin concentration did not change (54 +/- 11 pM at 75 days, 68 +/- 8 pM at 137 days), but there was a significant increase in the increment in plasma insulin concentration in response to a hyperglycemic clamp over this same period (deltaI pM/deltaG mM) from 20 +/- 3 at 75 days to 105 +/- 8 at 137 days (p < 0.001). The deltaI (pM) in response to arginine also increased from 129 +/- 17 pM at 75 days to 635 +/- 103 pM at 137 days (p < 0.001). Sustained hyperglycemia from 90 to 100 days reduced the deltaI (pM)/deltaG (mM) to glucose (13 +/- 2, p < 0.01) and the deltaI pM to arginine (369 +/- 86, p < 0.05) to values less than those found in euglycemic animals (deltaI/deltaG = 58 +/- 4 to glucose, deltaI = 525 +/- 71 to arginine). Thus, glucose and arginine stimulate insulin secretion at midgestation at 20% of the rate near term, and there is a consistently positive developmental pattern of insulin secretion to these secretagogues over the second half of gestation. Furthermore, chronic, high, relatively constant hyperglycemia blunts insulin secretion to glucose and arginine close to midgestation, similar to the effect seen near term. Such developmental and adaptive capacities may account for an important part of the variability in fetal glucose metabolism observed in animal models and human cases of diabetes during pregnancy.

Animals↗
PubMed1997

Technical and methodologic considerations for performance of indirect calorimetry in ventilated and nonventilated preterm infants.

OBJECTIVE: To evaluate and refine indirect calorimetry measurement techniques so that accurate metabolic measurements can be performed in mechanically ventilated and convalescing preterm infants who require supplemental oxygen. DESIGN: Laboratory validation of an indirect calorimeter; clinical and laboratory assessments of technical problems in performing metabolic measurements; and clinical indirect calorimetry studies in mechanically ventilated and nonventilated preterm infants. SETTING: Neonatal intensive care unit (ICU) in a tertiary care university hospital. PATIENTS: Level II and level III mechanically ventilated (n = 10) and nonventilated (n = 14) neonatal ICU patients who required FIO2 levels ranging from 0.21 to 0.42. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: System calibration was assessed by combustion of 100% ethanol; the mean respiratory quotient was 0.667 +/- 0.001 (SEM). In addition, oxygen consumption (Vo2) and CO2 production (Vco2) were simulated by CO2/nitrogen infusions within the range expected for 0.5- to 7-kg infants. Mean relative errors were 0.6 +/- 0.3% and 1.8 +/- 0.3% for expected Vo2 and Vco2 values, respectively. In 27 mechanically ventilated patients with no audible endotracheal tube leak, measured endotracheal tube leak ranged from 0.0% to 7.5%. Fluctuations in FIO2 during mechanical ventilation were monitored in 30-min studies, using wall-source (n = 27) or tank-source (n = 11) supplemental oxygen. Mean FIO2 variation was 0.00075 +/- 0.00013 vs. 0.00011 +/- 0.00001 using wall-source and tank-source oxygen, respectively. Some of the difficulties of obtaining accurate measurements in supplemental hood oxygen studies were overcome by using tank-source vs. wall-source oxygen and a unique hood design. CONCLUSIONS: Accurate indirect calorimetry studies can be performed in both ventilated and nonventilated infants weighing as little as 500 g, providing that sufficient attention is paid to technical and methodologic measurement details.

Calorimetry, Indirect↗
PubMed1997

Leucine metabolism in chronically hypoglycemic hypoinsulinemic growth-restricted fetal sheep.

We measured leucine flux rates during infusions of L-[1-14C]- and L-[1-1C]leucine in fetal sheep exposed to maternal insulin-induced hypoglycemia over the last 8 wk (40%) of gestation to determine effects of chronic glucose deficiency and hypoglycemia on fetal leucine metabolism. Compared with control fetuses (C, n = 5), hypoglycemic fetuses (HG, n = 8) weighed less (C, 3.43 +/- 0.07 kg; HG, 2.32 +/- 0.24 kg), had lower plasma glucose (C, 1.04 +/- 0.02 mM; HG, 0.59 +/- 0.01 mM), insulin (C, 48 +/- 6 pM; HG, 12 +/- 6 pM), and leucine concentrations (C, 195.6 +/- 8.3 microM; HG, 140.8 +/- 15.0 microM), lower rates of net leucine uptake (C, 4.2 +/- 0.6 mumol.min-1.kg-1; HG, 2.1 +/- 0.4 mumol.min-1.kg-1) and leucine flux into protein accretion (C, 2.8 +/- 0.2 mumol.min-1.kg-1; HG, 0.6 +/- 0.1 mumol.min-1.kg-1), and an increased rate of leucine release from protein breakdown (C, 1.1 +/- 0.1 mumol.min-1.kg-1; HG, 3.3 +/- 0.2 mumol.min-1.kg-1) (P < 0.05 for all). Plasma leucine disposal, flux into protein synthesis, and oxidation were not different between groups. We conclude that adaptations of fetal leucine metabolism to long-term hypoglycemia and decreased glucose apply represent diminished leucine uptake and increased leucine release from protein breakdown, which are associated with decreased incorporation of leucine into protein accretion and a slower rate of fetal growth.

Animals↗
PubMed1997

Separate and joint effects of arginine and glucose on ovine fetal insulin secretion.

To determine separate and joint effects of increases (delta) in fetal plasma concentrations of arginine (Af) and glucose (Gf) on fetal insulin (If) secretion (delta If), 15 late-gestation fetal sheep were given 5-min arginine bolus infusions (40, 86, 144, 201, and 402 mumol/kg estimated fetal wt) at 90 min of 120 min steady-state glucose clamps (basal Gf, basal + 0.6 mM Gf, and basal + 1.1 mM Gr), producing absolute and percent increases above basal Af of 25.8 +/- 1.3 microM (+33%), 50.9 +/- 6.3 microM (+66%), 83.8 +/- 7.1 microM (+108%), 122.1 +/- 9.4 microM (+156%), and 302.2 +/- 28.2 microM (+386%), respectively. Acute hyperglycemia alone produced an increase above basal If of 9 +/- I microU/ml (+80%) and 19 +/- 2 microU/ml (+170%) after basal + 0.6 mM Gf and basal + 1.1 mM Gf, respectively. Increasing values of delta Af showed separate but lesser effects on delta If, which were significant only at very high values of Af (> 100% above mean normal Af) unless marked hyperglycemia (1.5- to 2-fold normal) was also present, demonstrating joint effects of delta Af and delta Gf on delta If according to a best-fit inverse polynomial response surface. We conclude that physiological increases in Af at normal glucose concentrations are not a potent-stimulus to insulin secretion in fetal sheep.

Animals↗
PubMed1997

Fieller's theorem, Scheffé simultaneous confidence intervals, and ratios of parameters of linear and nonlinear mixed-effects models.

The issue of joint confidence region and simultaneous confidence interval estimation for ratios of the parameters of a nonlinear mixed-effects model is addressed using a Fieller's theorem approach. The method presented is similarly applicable to linear mixed-effects models. In addition, previous work on linear fixed-effects models is demonstrated to be a special case of the present method. The methodology is applied to the ratios of slopes in a study of gestational maturation of placental glucose transfer capacity in sheep.

Animals↗