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Biomedical subjects

M Silver

Publications and source records attributed to M Silver.

At least 163 records · Page 9Linked to original sources

Studies on equine prematurity 3: Insulin secretion in the foal during the perinatal period.

The factors influencing beta cell function in the foetal and neonatal foal have been investigated in chronically catheterised foetal foals and in newborn foals delivered either spontaneously at term or by induction at different gestational ages. Insulin was detected in the foetal plasma from as early as 150 days of gestation (term = 340 days) and during the last third of gestation the foetal beta cells responded to exogenous administration of glucose and arginine and to endogenous variations in the glucose level. Insulin secretion by the foetal beta cells was depressed by anaesthesia and surgery. At birth, there was a significant positive correlation between the plasma concentrations of insulin and glucose irrespective of the maturity at birth or type of delivery (r = 0.86, n = 39, P less than 0.01). The slope of this relationship was significantly less than that relating the postoperative foetal concentration but only when delivery was difficult or prolonged was the beta cell sensitivity to glucose completely abolished. At birth, there were no significant differences in the plasma concentrations of insulin or glucose between full term foals delivered spontaneously or by induction. However, the spontaneously delivered foals showed a transient increase in the insulin concentration 15 mins after birth which was not observed in the full term foals delivered by induction. Plasma glucose concentrations were maintained during the 2 h after birth in the absence of sucking in both the induced and the spontaneously delivered full term foals. Premature foals had significantly lower plasma glucose concentrations at birth than full term foals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Studies on equine prematurity 6: Guidelines for assessment of foal maturity.

This paper describes criteria used to assess maturity of the newborn foal and their clinical application to field cases of prematurity and dysmaturity. Premature and mature foals may be clearly distinguished by their behavioural and physical characteristics. Measurement of haematological parameters (mean cell volume, total white cell and differential counts), pancreatic beta cell activity (plasma glucose and insulin levels), adrenocortical-medullary function (plasma cortisol, adrenocorticotrophic hormone and catecholamines) and the renin-angiotensin system (plasma renin substrate concentrations) were found useful in evaluating the status of the newborn foal. Confirmation of the initial diagnosis can be made by response to various challenge tests eg, glucose tolerance test, short acting synthetic adrenocorticotrophic hormone (ACTH1-24) and frusemide. In the present investigation a small number of individuals appeared to be intermediate in maturity to the other two groups, indicating that a third state of maturity may be identified. The clinical implications of this work suggest that cortisol replacement therapy and administration of long acting synthetic ACTH1-24 may be of benefit.

Adrenocorticotropic Hormone↗

Cyclosporine in cardiac transplantation.

Since 1981 the authors have performed 14 orthotopic heart transplantations and one heart-lung transplantation, using cyclosporine and prednisone as immunosuppressants. Eight of the recipients had terminal congestive cardiomyopathy and six had ischemic cardiac dysfunction. The combined heart-lung transplantation was performed on a patient with a congenital ventricular septal defect with Eisenmenger's syndrome. Twelve of the patients were alive and well at follow-up 9 to 34 months (mean 17.4 months) after transplantation. One patient died of acute rejection and one of acute pancreatitis and secondary peritonitis. The third death, due to acute right ventricular failure, occurred immediately after transplantation. Rejection was diagnosed histologically on seven other occasions in four patients and was treated successfully. Infection was not a major problem. Cyclosporine -induced reversible nephrotoxicity was evident in 12 patients, 2 of whom required dialysis. Other side effects of cyclosporine seen in these patients included hypertension, gastrointestinal upset, headaches and hirsutism. This experience suggests that cyclosporine is a potent immunosuppressive agent that has greatly reduced the hazards of rejection and infection. However, the frequency of nephrotoxicity is high; careful monitoring of cyclosporine blood levels and renal function is essential.

Adolescent↗

Localization of basement membrane components after dermal-epidermal junction separation.

Adult human skin was separated at the dermal-epidermal junction (DEJ) by 4 published methods that involved different mechanisms of action: cold 1 M salt (tissue extraction), cold trypsinization (enzymatic), induction of a suction blister (mechanical), and warm phosphate-buffered saline (protease activation). The localization of DEJ macromolecules was studied after each separation method. By all of the methods tested, bullous pemphigoid antigen remained closely associated with the epidermis while laminin, the basement membrane heparan sulfate proteoglycan, and collagen types IV and V remained with the dermal side of the separation. The bullous pemphigoid antigen is, then, the DEJ component most closely associated with the epidermal basal cell. Of the basement membrane components tested, only the basement membrane heparan sulfate proteoglycan was trypsin-sensitive.

Adult↗

Adrenal cortex of fetal lamb: changes after hypophysectomy and effects of Synacthen on cytoarchitecture and secretory activity.

The effects of hypophysectomy on the cell population of the adrenal cortex has been examined with light and electron microscopy. The sensitivity of the adrenal cortical cells to exogenous ACTH in both normal and hypophysectomized fetuses has been investigated by comparing plasma cortisol concentrations with structural changes in the adrenal cortex. Hypophysectomy was carried out at about 100 d and the subsequent analysis was made at about 135 d on fetuses catheterized at least 6 d earlier. The zona fasciculata of intact fetuses contained about 25% mature and 75% immature cells at 130-136 d. After hypophysectomy this zone contained a uniform population of immature cells and no mature cells; there was a significant reduction in both adrenal weight and cortical thickness. The zona glomerulosa was unaffected by hypophysectomy. The infusion of Synacthen 0 . 25 mg/d I.V. for 48 h did not affect the zona glomerulosa but resulted in a 2-fold increase in the thickness of the zona fasciculata in hypophysectomized and intact fetuses. This cortical growth was due to both hypertrophy and hyperplasia. All the cells in the zona fasciculata were mature following Synacthen treatment in both groups. The most striking difference between the secretory response of the adrenal cortex to Synacthen in the two groups was found within 3-6 h of the onset of infusion. Within this period there was a significant increment in the plasma cortisol concentration in the intact fetuses while no response was observed in the hypophysectomized animals. After 12 h infusion by contrast, a steadily rising response was observed in both groups. There was a significant correlation between the final plasma cortisol concentration and both the adrenal weight and cortical thickness after 48 h treatment. The increased sensitivity of the adrenal cortex to exogenous ACTH as term approaches in the sheep is considered to be dependent upon the increasing proportion of mature zona fasciculata cells within the adrenal cortex.

Adrenal Cortex↗

The effect of the nutritional state on uterine prostaglandin F metabolite concentrations in the pregnant ewe during late gestation.

The effects of nutritional state and nutrient availability on arterial and uterine venous concentrations of 13, 14 dihydro-15-ketoprostaglandin F2 alpha (PGFM) have been investigated in chronically catheterized pregnant ewes during late gestation (120-144 d; term = 147 d). Before the daily feed of concentrates was given, a significant positive venous-arterial (V-A) difference in plasma PGFM concentration was observed across the uterus, irrespective of the number of fetuses or the gestational age (mean value at 135 +/- 2 d: 0.42 +/- 0.06 ng/ml, n = 13, P less than 0.01). However, by 3-5 h after feeding, no significant difference in PGFM concentration could be detected across the uterus. Withdrawal of food but not water for 48 h increased the plasma PGFM levels and widened the V-A difference in PGFM concentration across the uterus at all gestational ages studied but had the greatest effect in late gestation (greater than 137 d). These changes in plasma PGFM were accompanied by a fall in glucose and a rise in free fatty acid (FFA) concentration in the arterial plasma. When these metabolite changes were reversed at the end of the fast either by refeeding or by glucose infusion, there was a rapid fall in PGFM concentration and a narrowing of the uterine V-A difference. Induction of hypoglycaemia by infusion of insulin also led to a widening of the V-A difference in PGFM concentration across the uterus. There was a significant inverse correlation between the arterial plasma glucose level and the V-A difference in PGFM concentration across the uterus during feeding, fasting and insulin infusion. The V-A difference in PGFM concentration was also positively correlated with the arterial plasma FFA level under these conditions. When arterial plasma concentrations of PGFM rose above 3 ng/ml, during fasting or insulin induced hypoglycaemia, the ewes lambed within 12-24 h of restoring the metabolite concentrations. These observations indicate that the output of PGFM by the uterus is controlled in some way by the availability of nutrients and emphasize the importance of a regular food intake during late gestation in the ewes.

Animals↗

Fetal and maternal endocrine changes during the induction of parturition with the PGF analogue, cloprostenol, in chronically catheterized sows and fetuses.

Parturition was induced in 8 catheterized sows 24-27 h after a single injection of the prostaglandin F (PGF) analogue, cloprostenol (200 micrograms, intramuscular), given at 105-106 days (4 sows) and 109-111 days (4 sows); term = 115 days. All catheterized fetuses were in good condition during the course of the induction and a normal percentage of live births occurred, although the subsequent viability of the piglets appeared to depend on the presence of an adequate suckling reflex. Maternal endocrine changes following cloprostenol included: (1) a rapid drop in plasma progesterone, which fell to below 5 ng/ml within 4 h, (2) a subsequent rise in 13, 14 dihydro-15-oxo prostaglandin F (PGFM) at about 6 h, with an increase in the venous-arterial difference across the uterus, (3) a large prepartum rise in PGFM from about 12 h, (4) a transient rise and fall in plasma cortisol immediately after the cloprostenol and a subsequent rise during labour, and (5) no detectable change in total unconjugated plasma oestrogen. During failed induction (2 sows) maternal progesterone levels remained above 5 ng/ml. In the fetuses, no changes in plasma progesterone were detectable following cloprostenol or during labour although there was a significant increase at birth. Fetal plasma cortisol concentrations had increased significantly 2 h after the cloprostenol, but a much greater cortisol surge began at 16-20 h reaching a maximum at birth. Fetal plasma oestrogen levels also increased just before delivery. These findings show that when farrowing is induced prematurely, the majority of the maternal endocrine changes are similar to those preceding spontaneous labour. However, the gradual rise in fetal plasma cortisol, which normally begins 4-6 days before term, is circumvented; instead a very rapid fetal cortisol surge begins after rather than before the drop in maternal progesterone and rise in PGFM. This results in high neonatal plasma cortisol levels in both catheterized and non-operated piglets and may well account for their viability.

Animals↗

Pancreatic beta cell function in the fetal pig and sow.

Insulin secretion was investigated in acutely anaesthetized and chronically catheterized sows and their fetuses during late gestation. In the conscious animals, the mean fetal concentration of plasma insulin was 8.4 +/- 1.5 microunits/ml which was significantly less than the corresponding maternal value of 33.9 +/- 6.5 microunits/ml (n = 12, P less than 0.01). The plasma concentrations of insulin and glucose in the new-born piglets from these litters were not significantly different from the values observed in utero. The plasma concentration of insulin in the anaesthetized fetuses was significantly less than that in the chronically catheterized piglets over the same range of glucose levels. In the chronically catheterized animals, both fetal and maternal levels of insulin rose with increasing concentrations of plasma glucose while under acute conditions there was no correlation between the endogenous concentrations of insulin and glucose in either the fetuses or their mothers. Infusion of exogenous glucose (0.5 g as a 50% solution in 0.9% NaCl) stimulated the release of insulin in all the chronically catheterized fetuses studied but rarely increased the concentration of insulin in the anaesthetized fetusus. The present findings show that anaesthesia and surgery depress pancreatic beta cell function in the pig, particularly in the fetus.

Anesthesia, General↗

Potential of intense gamma-irradiation of host cells for analysis of virus-specified transcription and replication.

Intense gamma-irradiation from a cobalt source differentially affects macromolecular synthesis of cultured mammalian cells. Exposure of monkey BSC-1 or murine fibroblastic L2 cells to 40 or 70 krad (1 rad = 1 x 10(-2) J/kg) abolishes DNA and RNA synthesis almost entirely but reduces the formation of protein much less. A dose-response analysis of irradiation shows that synthesis of total RNA and the messenger component thereof, measured as the poly(A)-containing fraction, are equally diminished. Host cells in which formation of DNA and RNA are minimal can support normal or nearly normal replication and transcription rates of vesicular stomatitis and vaccinia viruses. Therefore, use of pretreatment with gamma-irradiation, as employed here, should prove to be generally useful in examining virus-related transcription under circumstances in which application of drugs affecting gene expression, such as actinomycin D, is deemed undesirable.

Animals↗

Response of the adrenal cortex to tetracosactrin (ACTH1-24) in the premature and full-term foal.

The changes in plasma cortisol concentration in the immediate postnatal period were examined in 3 groups of newborn foals and the response of the adrenal cortex to exogenous ACTH1-24 (tetracosactrin) was tested in 2 of these groups. In full-term Thoroughbred and Pony foals a rise in plasma cortisol occurred between 0 and 30 min after birth, whereas no significant cortisol changes could be detected within 2 h of birth in the group of prematurely delivered foals. These differences in plasma cortisol between term and premature foals were accompanied by differences in blood pH and lymphocyte and neutrophil counts. The high cortisol concentrations in the term animals declined to low levels by 4-12 h after birth. There was also a clear distinction between the responsiveness of the adrenal cortex to ACTH in the term and premature animals. When short-acting tetracosactrin was given as a single i.m. injection (0.125 mg), a rapid rise in plasma cortisol occurred in all term foals whereas no response was detected in the premature group during the same 2-h test period. The adrenal cortical response was also accompanied by a significant fall in the neutrophil/lymphocyte ratio at 2 h after the injection; no such change was seen in the premature animals. After a 24-h period of treatment with depot tetracosactrin (3 doses; 0.4, 0.2, 0.2 mg i.m.), a 2nd test with short-acting tetracosactrin led to a rise in plasma cortisol in term and pre-term foals during the 2-h test period. The depot tetracosactrin also appeared to cause a 3-fold increase in basal plasma cortisol levels in both groups.

Adrenal Cortex↗

Uterine prostaglandin F metabolite production in relation to glucose availability in late pregnancy and a possible influence of diet on time of delivery in the mare.

The production of uterine PGFM during different dietary states has been investigated in pregnant mares in late gestation. Arterial and uterine venous plasma concentrations of PGFM rose when food was withdrawn for 12-30 h and the V-A difference widened significantly. There was an inverse correlation between the rise in PGFM and the fall in plasma glucose during a fast, and a significant decrease in the A-V plasma glucose differences across the uterus. Plasma PGFM and free fatty acid concentrations before and during food withdrawal were also correlated but no uterine A-V difference in free fatty acids could be detected. An immediate fall in uterine PGFM levels occurred upon refeeding or infusion of glucose, which was more closely correlated with the rise in plasma glucose than the fall in free fatty acids, both of which occurred after restoration of nutrient. No detectable alterations in uterine blood flow occurred during a fast/feed cycle and hence A-V or V-A differences across the uterus gave an indication of uptake or output. PGFM production increased 5 times during a fast and glucose uptake decreased by about 70%. Basal levels were restored by 1-3 h after feeding or glucose infusion. Daily fluctuations in plasma PGFM concentrations were closely associated with the time of the morning feed of concentrates. The overnight rise in PGFM was greatest in late gestation. Five of the 8 mares delivered prematurely within 1 week of the last period of food withdrawal. Attention is drawn to the consequences of inadequate or intermittent feeding on premature delivery.

Animals↗