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Biomedical subjects

M Silver

Publications and source records attributed to M Silver.

At least 73 records · Page 4Linked to original sources
PubMed1995

Haemodynamic responses to an angiotensin II receptor antagonist (GR 117289) in maternal and fetal sheep.

An AT1-specific angiotensin II receptor antagonist (GR117289; 1 mg/kg I.V. bolus) was administered daily to ten chronically catheterized, normotensive ewes during late pregnancy (from 126 +/- 1 days) until parturition (139 +/- 1 days); five control animals received an equivalent volume of vehicle solution. Following drug administration, mean maternal blood pressure decreased from 87 +/- 1 mmHg to a minimum of 79 +/- 1 mmHg at 0.5 h (P < 0.05; n = 10) and remained low for 4-6 h without any concomitant change in fetal blood pressure or maternal and fetal heart rates. In animals fitted with flow probes, uterine blood flow decreased from 443 +/- 21 to 363 +/- 27 ml/min at 0.5 h post-drug (P < 0.05; n = 6); this change was positively correlated with the reduction in maternal blood pressure. The mean decrements in uterine and umbilical blood flows measured by steady-state infusion of tritiated water were -611 +/- 171 ml/min at 4-6 h (P < 0.05; n = 5) and -71 +/- 19 ml/min at 0.5-1 h (P < 0.05; n = 5), respectively. Significant reductions (P < 0.05; n = 10) in fetal arterial oxygen tension (-1.6 +/- 0.4 mmHg), saturation (-6.6 +/- 1.6%) and content (-0.3 +/- 0.1 mumol/ml) were evident at 0.5 h post-drug and were maintained for 6-12 h. Umbilical oxygen delivery decreased at 0.5-1 h following drug administration (P < 0.01; n = 5), but was unaccompanied by any significant change in fetal oxygen consumption. Chronic decreases in daily fetal pH and blood oxygen content occurred in GR117289-treated ewes. There were no significant differences in gestational length or neonatal outcome between vehicle- and GR117289-treated groups of ewes with single fetuses.

Angiotensin Receptor Antagonists↗
PubMed1995

The glucogenic capacity of the fetal pig: developmental regulation by cortisol.

In the present study, the ontogenic changes in gluconeogenic enzyme activities and in hepatic glycogen and beta-adrenergic receptor levels were investigated in fetal pigs from 70 days of gestation until delivery at term (114 +/- 2 days). The values were compared with those observed in fetuses infused subcutaneously with cortisol for 6 days beginning at 82-84 or 92-94 days of gestation. Tissue glucose-6-phosphatase (G6Pase) activity increased with increasing gestational age in the liver, kidney and duodenum of control fetal pigs. At birth, there was a further increase in G6Pase activity in the liver but not in the kidney or duodenum. In the kidney, there was a similar gestational increase in phosphoenolpyruvate carboxykinase (PEPCK) activity. These changes in enzyme activities closely paralleled the prepartum increase in fetal plasma cortisol and were accompanied by increases in hepatic glycogen content and beta-adrenergic receptor density. At 98-100 days, there were significant increases in G6Pase activity in the liver, kidney and duodenum of the cortisol-infused fetuses, whereas at 88-90 days only renal G6Pase was significantly elevated by cortisol infusion. Cortisol infusion also increased hepatic beta-receptor density at 88-90 days and hepatic glycogen content at both gestational ages. There were no changes in hepatic PEPCK, hepatic or renal fructose diphosphatase and aspartate amino transferase activities during cortisol infusion or with increasing gestational age. When the data from all the piglets were combined, irrespective of age or treatment, there were significant positive correlations between log plasma cortisol and G6Pase activity in the liver, kidney and duodenum. Similar positive correlations were observed between hepatic beta-adrenoceptor density and log plasma cortisol and between the latter values and the hepatic glycogen content. These findings show that cortisol induces tissue G6Pase activity in the fetal pig and suggest that the prepartum rise in endogenous cortisol may be responsible for the increase in fetal glucogenic capacity observed towards term in this as in other species.

Animals↗
PubMed1995

Sympathoadrenal and other endocrine and metabolic responses to hypoglycaemia in the fetal foal during late gestation.

In the present study, ten insulin challenge tests were carried out on nine chronically catheterized fetal foals between 253 and 314 days gestation (term > 320 days). Changes in fetal plasma concentrations of glucose, catecholamines, cortisol, ACTH, free fatty acid (FFA) and lactate were measured before and after a bolus dose of insulin (0.5-2.0 u/kg I.V.). Fetal blood gases, pH, haemoglobin levels and heart rate were measured throughout the 2-3h experimental period. The fetuses fell into two distinct groups on the basis of proximity to delivery and basal plasma cortisol and catecholamine levels. Those within 2-10 days of delivery after 300 days (group 2, number of experiments (n) = 4) had plasma cortisol and noradrenaline concentrations which were significantly higher (P < 0.05) than the corresponding values in fetuses sampled earlier in gestation or at least 2 weeks before foaling (group 1, n = 6). Although insulin administration resulted in a 50% fall in plasma glucose in all animals, group 2 showed significantly greater increases in plasma noradrenaline than group 1. In neither group were there detectable changes in plasma adrenaline. In group 2, increases in plasma cortisol were seen following insulin, whereas no cortisol changes were observed in group 1, despite rises in plasma ACTH. Insulin administration also led to acidosis and increases in heart rate and plasma lactate and FFA levels in all fetuses studied. However, only group 2 became consistently hypoxic during the insulin challenge. No significant changes in plasma glucose or any of the other parameters were observed in the fetuses after saline administration (n = 5). These findings suggest that hypoglycaemia activates the sympathoadrenal system in the fetal foal from 75% of gestation but has relatively little effect on the fetal pituitary-adrenocortical axis until much closer to term.

Adrenal Glands↗
PubMed1995

Glucose and oxygen metabolism in the fetal foal during late gestation.

With the use of [U-14C]glucose tracer methodology, the rates of umbilical uptake, utilization, oxidation, and production of glucose were determined in nine chronically catheterized fetal foals in the fed state between 268 and 325 days of gestation (term approximately 335 days). At the same time, the rates of umbilical O2 and lactate uptake were measured in all nine fetuses by Fick principle. The mean fetal rates of umbilical glucose uptake, glucose utilization, and CO2 production from glucose carbon were 36.9 +/- 2.5, 36.4 +/- 1.7, and 117.7 +/- 17.4 mumol.min-1.kg fetal body wt-1, respectively (n = 9). Endogenous glucose production was therefore negligible in the fetal foal in the fed state. Production of CO2 from glucose carbon accounted for 40.9 +/- 6.5% of the umbilical O2 uptake, which averaged 292 +/- 15 mumol.min-1.kg-1 (n = 9). No significant changes in fetal glucose or O2 metabolism were observed with increasing gestational age. The rates of umbilical glucose uptake, glucose utilization, and CO2 production from glucose carbon (P < 0.01), but not the rate of umbilical O2 uptake (P > 0.05), were positively correlated with the fetal blood glucose level. There was a significant umbilical lactate uptake in the fetuses older than 290 days (12.3 +/- 4.1 mumol.min-1.kg-1, n = 5, P < 0.05) but not in the younger animals (6.2 +/- 9.6 mumol.min-1.kg-1, n = 4, P > 0.05). Hence, glucose is used for both oxidative and nonoxidative metabolism in utero and is a major, although not the sole, oxidative substrate in the fetal foal during late gestation.

Animals↗
PubMed1995

The prenatal development and glucocorticoid control of brush-border hydrolases in the pig small intestine.

The development of brush-border enzymes and the possible regulatory role of cortisol were investigated in the small intestine of the fetal and neonatal pig. With the sows under pentobarbitone anesthesia, osmotic minipumps containing either saline or cortisol were inserted s.c. into 25 fetuses from 10 pregnant sows (82-96 d gestation). Six d later, the infused fetuses were removed by cesarean section and samples of the proximal, middle, and distal intestine taken for analysis. Samples were also obtained from 48 piglets that did not undergo an operation (controls) and that were removed at intervals from 82 d gestation until term (114 +/- 2 d). In the proximal and middle intestine, the mean levels of lactase-phlorizin hydrolase (EC 3.2.1.23-62), maltaseglucoamylase (EC 3.2.1.20), aminopeptidase N (EC 3.4.11.2), and aminopeptidase A (EC 3.4.11.7) increased during the last 10-15 d before term, correlated positively with log10 plasma cortisol values, and were higher in cortisol-infused than in saline-infused fetuses (p < 0.05). Activity of sucrase-isomaltase (EC 3.2.1.48-10) was low in fetal pigs, and this enzyme and dipeptidyl peptidase IV (EC 3.4.14.5) were not significantly affected by fetal age or exogenous cortisol. Maltase (EC 3.2.1.48-10 and EC 3.2.1.20) activity was significantly decreased in the middle and distal intestine of cortisol-infused fetuses. The results suggest that the prepartum rise in endogenous cortisol secretion stimulates the prenatal expression of certain brush-border enzymes in the pig small intestine at this critical time. However, the effects of cortisol on the developing intestine were highly idiosyncratic for particular enzymes and intestinal regions.

Aminopeptidases↗
PubMed1995

Ontogeny and ultradian rhythms of adrenocorticotropin and cortisol in the late-gestation fetal horse.

Fetal maturation and the timing of parturition in both sheep and primates are thought to be controlled by the hypothalamic-pituitary-adrenal axis but little is known about the endocrinology of the equine fetus. We investigated the ontogeny of plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol and corticosteroid binding capacity in the late-gestation fetal horse. We also wished to determine whether there is ultradian rhythmic release of ACTH and cortisol in fetal horses and we compared fetuses to maternal and non-pregnant adult horses. Six fetuses, 278-304 days gestation (term approximately 335), were catheterized and sampled daily until delivery. Mean (+/- S.E.M.) ACTH concentrations increased significantly from 159 +/- 21 to 246 +/- 42 pg/ml over the last 2 days before parturition. Fetal cortisol increased significantly from 3.1 +/- 1.0 to 13.4 +/- 3.7 ng/ml (mean +/- S.E.M.) over the last 9 days before delivery. The slope of regressions for ACTH and cortisol concentrations with respect to time were positive in all subjects and statistically significant in 3 of 6 for ACTH and 5 of 6 for cortisol. Fetal corticosteroid binding capacity declined from 49.5 +/- 20.5 to 16.1 +/- 2.2 ng/ml (mean +/- S.E.M.) over the last 10 days before parturition. However, the greatest changes in ACTH, cortisol and corticosteroid binding capacity occurred very late in gestation, during the last 48 to 72 h before parturition.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity Cycles↗
PubMed1994

Release of lipid from the equine placenta during in vitro incubation.

An in vitro incubation technique was used to examine release of lipids from the equine placenta. Placental tissue was obtained at term (n = 5, term = 320-365 days) and earlier in gestation (n = 8, mean = 266 days). Term placentae were incubated at two temperatures, 4 degrees C (control) and 37 degrees C for 2 h. Pre-term placentae were incubated at 37 degrees C with two different concentrations of fatty acid in the medium. Tissues and media were analysed for their lipid concentrations. Term and pre-term placentae released free fatty acid (FFA) and phospholipid into the incubation medium during incubation at 37 degrees C. Long chain polyunsaturated fatty acids derived from the essential fatty acids were released into the media. The fatty acid profiles of the lipids released during incubation more closely resembled those of fetal plasma than maternal plasma lipids as measured in previous studies. These data are consistent with the view that the equine placenta is a source of both FFA and phospholipid for the fetus and that the placenta may provide long chain polyunsaturated fatty acids for the fetal foal.

Animals↗
PubMed1994

Placental progestagens in the sheep and horse and the changes leading to parturition.

Placental progestagen production and metabolism during pregnancy, the changes which precede parturition and the extent of fetal involvement in the latter processes are compared in the sheep and the horse. Neither species requires the presence of a corpus luteum for maintenance of the latter part of pregnancy, but the mechanisms involved in placental progesterone/progestagen production are very different in the two species. In sheep the primary product is progesterone (P4), levels of which are high in the maternal but not the fetal circulations. By contrast, in the mare P4 is not detectable in maternal blood after 200 days gestation although it is present in the placenta and fetal circulation. A range of P4 metabolites (primarily 5 alpha-pregnanes) are produced by the equine placenta, while in the fetus pregnenolone and its metabolites are the predominant progestagens. In sheep the prepartum endocrine cascade in which the rise in fetal cortisol stimulates enzyme changes in the placenta so that P4 declines and estrogens and prostaglandins eventually rise, is fairly well established compared with the events preceding delivery in the mare. In the latter species there is a gradual rise in progestagens for 10-20 days before term, at a time when the fetal adrenal is relatively quiescent and unresponsive to ACTH i.e. fetal cortisol levels are low. In the last 24-48 h before delivery maternal progestagens fall, just after fetal plasma cortisol concentrations begin to escalate. The ways in which maternal and fetal prepartum endocrine changes may be interrelated and the possibility of a fetal trigger to parturition in the mare are discussed.

Animals↗
PubMed1994

Nutritional regulation of uteroplacental prostaglandin production and metabolism in pregnant ewes and mares during late gestation.

Prostaglandins (PGs) are produced by a variety of uteroplacental tissues during pregnancy and are released into the fetal fluid sacs and both the uterine and umbilical circulations. Uterine PG output increases towards term and is enhanced by maternal undernutrition in pregnant ewes and mares. In both species, withdrawal of food but not water for 30-48 h increases uterine venous PG levels and the uterine venous arterial concentration differences in PGE and 13, 14, dihydro-15-keto-prostaglandin F2 alpha (PGFM), the stable metabolite of PGF2 alpha. The increments in uterine V-A concentration differences in PGE and PGFM increase towards term and are associated with raised plasma PG levels in the fetal circulation. The PG changes observed during fasting are closely related to the fall in plasma glucose and the rise in plasma FFA in peripheral plasma. When normal metabolite levels are restored either by refeeding or glucose infusion, there is a rapid fall in PG levels with a narrowing of the uterine V-A concentration differences in the ewe and mare. When the data from all the animals are combined, there is an inverse correlation between uterine glucose uptake and PGFM output in both the pregnant ewe and mare. The availability of glucose and FFA to the gravid uterus therefore has an important role in controlling uteroplacental PG production and metabolism in late gestation although the specific steps in biochemical pathways regulated by these metabolites remain unclear. In the ewe, fasting increases uterine contractility and leads to early delivery of viable lambs in animals close to term (> 95% gestation), whereas in the mare it causes premature delivery of non-viable foals in most animals in late gestation (> 80% gestation). Nutritionally induced changes in uteroplacental PG production and metabolism therefore have important consequences for the outcome of pregnancy and may have a pivotal role in the induction of labour both before and at normal term.

Animal Nutritional Physiological Phenomena↗
PubMed1994

Developmental regulation of the porcine exocrine pancreas by glucocorticoids.

The possible role of cortisol in development of the exocrine pancreas was investigated. In the first study, fetal pigs were removed from the uterus by caesarean section (pentobarbitone anesthesia) and the pancreas collected from 51 69 to 109-day-old fetuses (term = 114 +/- 2 days). Of these, 15 88 to 90-day-old fetuses had been infused subcutaneously for 6 days with either saline, adrenocorticotropic hormone or cortisol (osmotic mini-pumps implanted at 82-84 days). The pancreas was also removed from eight newborn pigs. Quantitative enzyme analysis showed that amylase and trypsin activities per milligram pancreatic protein increased toward term, correlated positively with fetal plasma cortisol (p < 0.01) and were stimulated by cortisol infusion (p < 0.05). In the second study, pigs were delivered by caesarean section 2-3 days before term (to circumvent the neonatal cortisol surge) and injected intramuscularly with saline (n = 11), metyrapone (an inhibitor of cortisol synthesis, n = 12), adrenocorticotropic hormone (n = 14) or cortisol acetate (n = 6) during the postnatal period. At 6-7 days of age, adrenocorticotropic hormone- and cortisol acetate-treated pigs had higher concentrations of amylase and trypsin in pancreas than metyrapone-treated pigs. The values in saline-injected pigs were intermediate. By gel electrophoresis and subsequent incubation with enzyme substrates, protease E, chymotrypsin C, and cathodic trypsin were first detected at 6-7 days of age, and the activities (semiquantitative densitometry) appeared lower in metyrapone-treated pigs than in pigs from other treatment groups. The results indicate that glucocorticoids stimulate the perinatal development of pancreatic enzymes in the pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Secretion of acid, gastrin, and cobalamin-binding proteins by the fetal pig stomach: developmental regulation by cortisol.

The role of cortisol in the development of gastric function was investigated in the fetal pig. Pregnant sows (term = 114 +/- 2 days, n = 10) were anaesthetized (pentobarbitone) and osmotic minipumps containing either saline or cortisol inserted subcutaneously into fetuses at 82-84 (n = 11) or 91-96 (n = 14) days gestation. Six days later the infused pigs were removed by Caesarean section and the stomach and its contents collected for analysis. Samples were also obtained from unoperated (control) fetal pigs (n = 51) removed under anaesthesia at intervals from 70 days gestation until term. The concentrations of acid in gastric fluid, gastrin in plasma and antral tissue (bioactive as well as precursor forms), and cobalamin(CBL)-binding proteins in fundic tissue were low in control pigs until 100 days gestation. During the last 2 weeks before term, large increases occurred in gastric fluid acidity (from pH 6-7 to pH 3 at birth), plasma amidated gastrin (from 10 to 90 pM) and CBL-binding protein concentration (from 10 to 80 pmol (g fundus)-1). These changes occurred in parallel with a surge in plasma cortisol (from 20 to 200 ng ml-1). Immature fetuses infused with cortisol had significantly higher gastric acidity, plasma amidated gastrin, and concentration of CBL-binding proteins than the corresponding control fetuses (P < 0.05). Across age and treatment groups, significant correlations were found between log10 plasma cortisol values and the above parameters (r = 0.59-0.76, P < 0.01). The results suggest that endogenous cortisol secretion stimulates the secretion of gastric acid, gastrin and CBL-binding proteins in the prenatal period of the pig.

Animals↗
PubMed1994

Blood amino acids in the pregnant mare and fetus: the effects of maternal fasting and intrafetal insulin.

Blood amino acids were measured in twelve chronically catheterized mares and fetuses between 250 and 310 days gestation. The concentrations of the majority of individual amino acids were similar in maternal and fetal arterial blood and no gestational changes were detected. Only methionine, phosphoserine, 3-methyl-histidine and glutamine were consistently higher in the fetus than the mare, whilst certain other amino acids were higher in the maternal blood. Fasting the mares for 36 h led to significant falls in plasma glucose and rises in urea and maternal free fatty acids (FFA). Small but significant decreases in a few amino acids were seen in both fetus and mother, with an overall amino acid fall of 15% in the fetus and 13% in the mare. Virtually all amino acids had risen to basal values by 6 h after feeding. Intrafetal insulin (1 i.u./kg I.V.) as a bolus caused a more dramatic fall in fetal glucose than fasting, with no change in the mare. There were also rapid decreases in many amino acids by 30 min post-insulin and by 2 h all but five amino acids had fallen significantly. There was a drop in total fetal blood amino acids of 29%. These findings show that, in contrast to most other species studied, there is no overall feto-maternal gradient in blood amino acids in the mare, and that fasting leads to small falls in amino acid concentration, whereas intrafetal insulin induces a severe hypoglycaemia with dramatic decreases in almost all amino acids and no change in urea, suggesting a direct anabolic effect of insulin on fetal tissues.

Amino Acids↗
PubMed1994

The role of parathyroid hormone-related protein in calcium homeostasis in the fetal pig.

The concentrations of plasma parathyroid hormone-like bioactivity and parathyroid hormone-related protein (1-86) (PTHrP) immunoreactivity were both higher in fetal pigs than in their mothers during the last 3 weeks of gestation. Both activities changed inversely with alterations in the plasma ionized calcium concentration. The data suggest that PTHrP may have a role in calcium homeostasis in the fetal pig, similar to its postulated role in sheep in the stimulation of calcium transport across the placenta.

Animals↗
PubMed1994

Adrenocortical stimulation of stomach development in the prenatal pig.

Development of the porcine gastric proteases (chymosin, pepsin A, B and C) has been studied in the fetal pig in the last third of gestation (term 115 days). The possibility that the prepartum rise in circulating cortisol is involved in gastric maturation was investigated by infusing immature fetuses with cortisol (osmotic minipumps implanted at 82-90 days of gestation). Concentrations of prochymosin in fundic tissue and stomach contents increased before term, correlated positively with log10 plasma cortisol values (r = 0.68-0.76, p < 0.001), and were stimulated by cortisol infusion (p < 0.001). The pH of stomach contents decreased (from pH 7 to 3), correlated negatively with log10 plasma cortisol values (r = -0.69, p < 0.001), and was reduced by cortisol infusion (p < 0.05). Only trace amounts of pepsinogens could be detected in fetal pigs. By immunohistochemistry, it was shown that cortisol increased the number and distribution of prochymosin-containing cells in the fundic gland. Stimulating effects were also observed for the small populations of pepsinogen-reactive cells present in some of the fetal pigs. The results suggest that endogenous cortisol stimulates the rise in prochymosin synthesis and secretion together with increased gastric acidity in the prenatal period of the pig.

Adrenocorticotropic Hormone↗
PubMed1994

Prepartum adrenocortical maturation in the fetal foal: responses to ACTH.

The present study was carried out on 19 chronically catheterized mares and fetuses in late gestation (term > 320 days). In six animals which were monitored up to the time of delivery of a live foal, plasma and amniotic fluid cortisol concentrations remained low until 4-5 days before parturition when there was a rapid, significant rise (P < 0.05) which was not accompanied by any corresponding changes in maternal plasma cortisol. Circulating fetal ACTH concentrations became more variable close to delivery and ANOVA revealed no significant increases during this critical period, although a negative correlation between plasma ACTH and time to delivery was observed (P < 0.05). Tests on fetal adrenal responsiveness to exogenous ACTH1-24 were carried out on ten animals. Before 295 days of gestation no significant increases in fetal plasma cortisol above its basal level of 20-30 nmol/l could be elicited by ACTH, administered as a single i.v. injection (1-2 micrograms/kg). By 304 +/- 3 days (mean +/- S.E.M.) small but significant (P < 0.05) increments in plasma cortisol were detected after ACTH, while in the oldest group (313 +/- 2 days) significant (P < 0.01) 50-60% increments were seen throughout the test period (2 h). Only one fetus was tested within 3 days of delivery and here a fourfold rise in plasma cortisol was evoked by ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1994

The technique of pleurodesis.

Pleurodesis may be indicated for pleural effusions (with careful patient evaluation) or recurrent pneumothoraces. It is contraindicated if tube thoracostomy fails to reexpand the lung and, possibly, if patients are candidates for lung transplantation or have congestive heart failure. We perform pleurodesis through an indwelling chest tube (alternative methods are thoracoscopy and thoracotomy). Common sclerosants include talc, doxycycline, minocycline, and bleomycin. Intrapleural administration of lidocaine may control pain, but injections of morphine or meperidine almost always are needed.

Aftercare↗
PubMed1993

Prostaglandin-induced antral hyperplasia in neonates: clinical experience and dose-response characteristics.

Antral hyperplasia (AH) induced by prostaglandins (PG) has been described by us recently in 5 infants with cyanotic heart disease receiving the drug. The purpose of the present study was to analyze 14 infants diagnosed as having AH either sonographically or pathologically in an attempt to characterize the dose-response characteristics of this adverse drug reaction, its clinical course and its optimal management. Infants with AH exhibiting large gastric aspirates have received a significantly lower cumulative dose (1,633 +/- 1,266 micrograms/kg) than those presented also with a palpable mass (3,458 +/- 1,703 micrograms/kg), (p < 0.01). While in general there is a dose-related clinical toxicity, variability in the location of the hyperplasia can explain cases of no apparent obstruction despite large cumulative doses of PG. In asymptomatic cases the antral hyperplasia, although visualized, it did not result in gastric outlet obstruction. In all cases followed by us to date, discontinuation of the PG has resulted in resolution of the clinical and sonographic findings. Nasojejunal tube was successfully attempted in several cases, preventing surgery in these very-high-risk infants.

Dose-Response Relationship, Drug↗