PubMed Health⌕ Search

Biomedical subjects

C T Jones

Publications and source records attributed to C T Jones.

At least 127 records · Page 7Linked to original sources

Studies on experimental growth retardation in sheep. The effect of removal of a endometrial caruncles on fetal size and metabolism.

Experimental intrauterine growth retardation was studied in sheep. Endometrial caruncles (anlagen of maternal cotyledon) were removed before pregnancy and at a second operation, catheters were implanted into the ewe and fetus at 105-135 days of pregnancy. Three groups of fetuses were defined: low birthweight-for-dates (small-caruncle), normal birthweight-for-dates (normal-sized-caruncle) from ewes which had endometrial caruncles removed and the controls. The mean placental weights in these groups were 139 plus or minus 5 g, 283 plus or minus 46 g, 334 plus or minus 22 g respectively. The brains, kidneys and adrenals of the small-caruncle-fetuses were significantly greater in proportion to body weight than in the controls and the appearance of ossification centres was delayed. Arterial oxygen tension was lower and packed cell volume higher in the small-caruncle-fetuses (PaO2 15 plus or minus 0.6 mmHg; packed cell volume 37.3 plus or minus 1.6%) and normal sized caruncles (PaO2 20.7 plus or minus 1.2 mmHg; packed cell volume 35.2 plus or minus 0.7%) than in the controls (PaO2 23.2 plus or minus 0.7 mmHg; packed cell volume 29.8 plus or minus 0.7%). Plasma concentrations of glucose (0.65 plus or minus 0.12 micromol/ml), lactate (0.9 plus or minus 0.1 micromol/ml) and pyruvate (0.08 plus or minus 0.025 micromol/ml) were lower in small-caruncle fetuses than in the control fetuses (glucose 1.05 plus or minus 0.06 micromol/ml, lactate 1.83 plus or minus 0.7 micromol/ml, pyruvate 0.21 plus or minus 0.06 micromol/ml). The corresponding values for the normal-sized-caruncle fetuses were glucose 0.71 plus or minus 0.12, lactate 1.18 plus or minus 0.7 and pyruvate 0.12 plus or minus 0.03 micromol/ml. The plasma concentration of alanine in the small-caruncle-fetuses (0.25 plus or minus 0.09 micromol/ml) was higher than in the normal-sized-caruncle (0.073 plus or minus 0.009 micromol/ml) or control fetuses (0.12 plus or minus 0.013 micromol/ml). The results indicate that fetal growth retardation due to restriction of placental growth after removal of endometrial caruncles is associated with chronic hypoxaemia, polycythaemia and hypoglycaemia. The restriction of nutrient supply probably accounts for the altered pattern of fetal growth but the relative importance of the changes observed remains uncertain.

Age Determination by Skeleton↗

Some effects of glucose concentration and anoxia on glycolysis and metabolite concentrations in the perfused liver of fetal guinea pig.

Effects of glucose concentration and anoxia upon the metabolite concentrations and rates of glycolysis and respiration have been investigated in the perfused liver of the fetal guinea pig. In most cases the metabolite concentrations in the perfused liver were similar to those observed in vivo. Between 50 days and term there was a fall in the respiratory rate and in the concentration of ATP and fructose 1,6-diphosphate and an increase in the concentration of glutamate, glycogen and glucose. Reducing the medium glucose concentration from 10 mM to 1 mM or 0.1 mM depressed lactate production and the concentration of most of the phosphorylated intermediates (except 6-phosphogluconate) in the liver of the 50-day fetus. This indicates a fall in glycolytic rate which is not in accord with the known kinetic properties of hexokinase in the fetal liver. Anoxia increased lactate production by, and the concentrations of, the hexose phosphates ADP and AMP in the 50-day to term fetal liver, while the concentration of ribulose 5-phosphate, ATP and some triose phosphates fell. These results are consistent with an activation of glycolysis, particularly at phosphofructokinase and of a reduction in pentose phosphate pathway activity, particularly at 6-phosphogluconate dehydrogenase. The calculated cytosolic NAD+/NADH ratio for the perfused liver was similar to that measured in vivo and evidence is presented to suggest that the dihydroxyacetone phosphate/glycerol 3-phosphate ratio gives a better indication of cytosolic redox than the lactate/pyruvate ratio. The present observations indicate that phosphofructokinase hexokinase and possibly pyruvate kinase control the glycolytic rate and that glyceraldehyde-3-phosphate dehydrogenase is at equilibrium in the perfused liver of the fetal guinea pig.

Adenine Nucleotides↗

The cardiovascular effects of circulating catecholamines in fetal sheep.

1. Adrenaline and noradrenaline have been infused into the fetal sheep to produce plasma concentrations comparable to those seen during hypoxia and the cardiovascular changes compared with those seen in response to hypoxia. The effect of isoprenaline, methoxamine, and beta- and alpha-adrenergic antagonists were also investigated. 2. There were no significant changes in the blood gas values during any of the infusions except for a mean fall in pH of 0.04 during adrenaline infusion. 3. Adrenaline caused a fall in the fetal heart rate followed by a rise above the control value after 15-20 min. The fall in heart rate was abolished when the rise in blood pressure was blocked with phentolamine. The rise in heart rate was blocked by propranolol. The exact cause of the biphasic changes in heart rate during adrenaline infusion is not clear. 4. A fall in heart rate was not seen with noradrenaline; a small rise was. Propranolol changed this into a fall in heart rate while phentolamine increased the size of the heart rate rise. 5. Phentolamine alone increased the fetal heart rate by 25% and reduced blood pressure by 12%; propranolol alone reduced heart rate by 14% and had no effect on blood pressure. Isoprenaline increased fetal heart rate and reduced blood pressure. 6. The incidence of fetal breathing movements was highly variable. Despite this a significant increase was observed during adrenaline infusion. None of the other infusions had consistent effects. 7. The role of the circulating catecholamines in mediating or modifying the cardiovascular responses to hypoxia in the fetal sheep is discussed.

Animals↗

The metabolic and endocrine effects of circulating catecholamines in fetal sheep.

1. Adrenaline and noradrenaline have been infused into the fetal sheep to produce plasma concentrations comparable to those seen during hypoxia. The effects have been compared with those of isoprenaline and methoxamine and the sensitivity to beta- and alpha-adrenergic antagonists has been followed. 2. Adrenaline caused an alpha-mediated increase in blood glucose that is associated with a fall in plasma insulin concentration. It also caused a beta-mediated increase in plasma lactate, free fatty acid and amino acid concentrations. 3. Noradrenaline was much less effective than adrenaline at eliciting metabolic responses. It had not cause a significant change in plasma glucose concentration, although this was associated with a small increase in plasma insulin concentration. It caused a small rise in the concentration of lactate and free fatty acids in fetal plasma but had no effect on plasma amino acids. 4. The beta- and alpha-adrenergic antagonists propranolol and phentolamine alone were without effect on any of the plasma metabolites or hormones assayed. Isoprenaline increased plasma glucose, lactate, free fatty acid, alanine and insulin concentrations, while methoxamine only increased plasma glucose and lactate, and this was associated with a fall in insulin concentration. 5. The concentration of ACTH in fetal plasma was increased by adrenaline and to a lesser extent by noradrenaline and methoxamine; these were blocked by phentolamine. Isoprenaline also caused a small increase in ACTH. There were no corticosteroid changes associated with the increase in ACTH. 6. The results have been discussed in relation to the adrenergic and pancreatic control of metabolism in the fetal sheep.

Adrenocorticotropic Hormone↗

Induction of premature parturition in sheep: adrenocorticotrophin and corticosteroid changes during infusion of Synacthen into the foetus.

Synacthen (10 microgram/h) infused into foetal sheep at about day 125 of gestation caused premature delivery within 4 days. During the first 24 h of the infusion the secretion of adrenocorticotrophin was depressed and the assayable hormone concentration was within 500-1000 pg/ml. Subsequently, large fluctuations occurred in the adrenocorticotrophin concentration in the plasma of foetal sheep which were consistent with the stimulation of adrenocorticotrophin secretion. No transfer of Synachthen to non-infused twin foetuses was observed. The plasma corticosteroid concentration in the infused foetus also showed a small rise during the first 24 h of the infusion followed by large fluctuations in concentrations that coincided with the changes in adrenocorticotrophin. No consistent changes in the plasma corticosteroid concentration in the non-infused twin foetus were observed. These results are discussed in relation to the hormone changes occurring during normal delivery.

Adrenal Cortex Hormones↗

Adrenocorticotrophin and corticosteroid changes during dexamethasone infusion to intact and synacthen infusion to hypophysectomized foetuses.

Synacthen has been infused at 10 microgram/h into 4 hypophysectomized foetal sheep. This caused a rise in adrenocorticotrophin to a mean value of 512 pg/ml which remained fairly constant and did not show the large fluctuations seen on infusion into intact foetuses. The Synacthen half-life in the circulation had a mean value of 0.27 min. Hypophysectomy did not necessarily delay the foetal corticosteroid response to Synacthen infusion. The corticosteroid concentration achieved had a mean value of about 50 ng/ml which is substantially below that for intact foetuses and in one case it was maintained at only 20 ng/ml. Despite this delivery occurred within 5 days. Dexamethasone infusion reduced the plasma adrenocorticotrophin concentration by about 70% and the plasma cortisol concentration by about 60%.

Adrenal Cortex Hormones↗

The development of some metabolic responses to hypoxia in the foetal sheep.

1. Foetal and maternal plasma metabolite and catecholamine concentrations have been measured in chronically catheterized sheep, 95-145 days pregnant. 2. With increasing gestational age there was rise in foetal plasma lactate, free fatty acid and ketone body concentration and in maternal plasma in free fatty acid and ketone body concentration. With the exception of alpha-amino nitrogen none of the plasma metabolites showed any correlation with foetal blood gas or pH values; alpha-amino N was inversely related to foetal blood pH. 3. Hypoxia in the foetuses was induced by causing the ewe to breathe 9% O2 with 3% CO2 in N2. This had a small effect on plasma metabolites in the ewe, mainly producing an increase in free fatty acid and ketone body concentration. 4. In the foetus hypoxia was associated with a large rise in plasma lactate and a small rise in alpha-amino N, the magnitudes of which did not change over the gestational range studied. Consistent and large increases in foetal plasma glucose, free fatty acid and ketone body concentration in response to hypoxia were seen only between 130 and 145 days. 5. In foetuses of 130-145 days the magnitude of the hypoxia-induced rise in plasma glucose and free fatty acid concentration was proportional to the plasma catecholamine concentration. 6. The concentration of acetate in foetal plasma was lower than and proportional to that in the maternal plasma. Neither concentration changed significantly during hypoxia. 7. The results are discussed in relation to the ability of the foetal sheep independently to control the concentration of its plasma metabolites and to mobilize its carbon stores at times of need. They indicate that in the sheep plasma catecholamines are important regulators of plasma glucose and free fatty acid concentrations late in foetal life.

Acetates↗

Some experiments on the role of the foetal pituitary in the maturation of the foetal adrenal and the induction of parturition in sheep.

The effect of repeated increases in plasma ACTH on the production of corticosteroids and androstenedione in the sheep foetus has been investigated. Elevation of foetal plasma ACTH for up to 2 h every 24 h by repeated periods of hypoxia increased the output of cortisol. No consistent effects on foetal or maternal androstenedione concentrations or on maternal oestrogen levels were observed. Repeated short periods of increased foetal plasma ACTH concentration may promote maturation of the foetal adrenal, but there is no increase in androgen secretion by the gland nor is there an increase in oestrogen production by the placenta under such conditions.

Adrenal Cortex Hormones↗

Developmental changes in the responses of the adrenal glands of foetal sheep to endogenous adrenocorticotrophin, as indicated by hormone responses to hypoxaemia.

The change in plasma ACTH and corticosteroid concentrations in response to a 60 min period of hypoxaemia were studied in foetal and adult sheep during the latter half of pregnancy. Hypoxaemia consistently caused large rises in the concentration of ACTH in foetal plasma, the magnitude of which did not change with gestational age but was related to the physiological state of the foetus. Before 139 days small and slow rises in corticosteroid (predominantly cortisol) concentration in foetal plasma were observed during hypoxaemia, and these may have been of maternal origin. After 139 days, hypoxaemia caused a rapid and large rise in the concentration of cortisol and corticosterone in foetal plasma, which was largely of foetal origin. Hypoxaemia caused no consistent change in maternal plasma ACTH concentration but was associated with progressive increases in plasma cortisol concentrations. The cortisol: corticosterone ratio in foetal plasma was 1-5 before 139 days and increased to 4-1 several days before term which was lower than the value of 9 in maternal plasma. Small concentrations of 11-deoxycortisol and cortisone were detected in maternal and foetal plasma, the changes of which were small during hypoxaemia. The results indicate that a maturational change in the sensitivity of the foetal adrenal to endogenous ACTH occurs several days before term.

Adrenal Glands↗

Changes in the concentration of adrenocorticotrophin and corticosteroid in the plasma of foetal sheep in the latter half of pregnancy and during labour.

The changes in plasma ACTH concentration of pregnant sheep and their foetuses during the latter half of pregnancy and during labour were studied. Before 140 days of gestation the mean concentration in foetal arterial plasma was 117+/-19 (S.E.M.) pg/ml which rose to a mean of 286+/-63 pg/ml. The rise in ACTH occurred at about the same time as, but not before, the rise in corticosteroid concentration in foetal plasma. The maternal plasma ACTH concentration did not change during the latter half of pregnancy and had a mean concentration of 64+/-9 pg/ml. During labour there was a progressive rise in the ACTH concentration in foetal plasma which was not associated with any corticosteroid changes. Ethanol did not suppress labour but reduced the ACTH concentration in foetal plasma.

Adrenal Cortex Hormones↗

Control of adrenocorticotrophin secretion by catecholamines in the pregnant and foetal sheep.

The effect of adrenaline on the maternal and foetal plasma ACTH concentration of twelve pregnant sheep with chronically implanted vascular catheters has been studied. Adrenaline infused into the jugular vein of the ewe or foetus produced carotid arterial adrenaline concentrations of 1-9 ng/ml. The foetal plasma ACTH was 253 +/- 73 pg/ml and it showed a fivefold increase during adrenaline infusion; the ACTH concentration achieved was proportional to the plasma adrenaline. In the ewe plasma ACTH was 99 +/- 23 pg/ml. During adrenaline infusion to the ewe this rose by an amount dependent on the adrenaline concentration achieved and there was also a rise in foetal plasma ACTH but no consistent change in foetal plasma adrenaline. There was no reproducible change in plasma corticosteroid concentration during adrenaline infusion into the foetus but a rise in maternal plasma corticosteroid concentration during infusion into the ewes. Because the adrenaline concentrations achieved during the infusions were within the physiological range, the results indicate that circulating catecholamines may directly or indirectly influence the concentration of ACTH in the circulation. Also, physiological rises in plasma catecholamines in pregnant animals may stimulate the release of ACTH from the foetal pituitary.

Adrenocorticotropic Hormone↗

Steroid and prostaglandin concentrations in the plasma of pregnant ewes during infusion of adrenocorticotrophin or dexamethasone to intact or hypophysectomized foetuses.

Catheters were implanted into 16 ewes and their foetuses between days 110 and 124 of gestation. Hypophysectomy was attempted in eight of these foetuses. Continuous infusion of synthetic ACTH (10 microgram/h) or dexamethasone (1mg/24 h) into the foetus, starting between days 124 and 129, induced premature parturition. The concentration of progesterone in the maternal peripheral plasma decreased before parturition in all animals while the level of oestradiol increased in ewes with intact foetuses or in those in which hypophysectomy was incomplete. When hypophysectomy was complete, no increase in the maternal level of oestradiol occurred before delivery. The concentration of 13,14-dihydro-15-oxo-prostaglandin F2alpha increased in the peripheral plasma of ewes with intact or hypophysectomized foetuses infused with ACTH. It is suggested that an intact foetal pituitary gland is required for the rise in the level of oestrogen prepartum, but that this rise is not essential for increased prostaglandin production of parturition.

Adrenocorticotropic Hormone↗

Lipid metabolism and mobilization in the guinea pig during pregnancy.

The liver of the foetal guinea pig accumulates a large quantity of triacyglycerol late in gestation at the same time that adipose-tissue mass grows at its maximum rate and foetal adipose-tissue lipoprotein lipase activity and sensitivity to lipolytic hormones has substantially declined. The fatty acid for triacyglycerol synthesis is not synthesized in the foetal liver and it is unlikely that it originates from any of the foetal tissues. Before the accumulation of hepatic triacyglycerol the concentration of free fatty acids increases in both the umbilical vein and the maternal inferior vena cava. This occurs at a time when the triacyglycerol lipase activity in maternal adipose tissue is elevated and the rate of lipolysis, but not of fatty acid esterification, is higher than earlier in gestation or than in the non-pregnant state. It is proposed that the increase in lipolysis in maternal adipose tissue, brought about by an increase in circulating lipolytic hormones, mobilizes fatty acid, which passes to the foetus and is partly stored as hepatic triacylglycerol. The foetal liver effectively removes both long-and short-chain fatty acids from umbilical-vein blood. The rate of placental fatty acid transfer is more than adequate to account for the triacylglycerol accumulation.

Acetates↗