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Biomedical subjects

S McArthur

Publications and source records attributed to S McArthur.

12 recordsLinked to original sources
PubMed2006

Perinatal glucocorticoid treatment disrupts the hypothalamo-lactotroph axis in adult female, but not male, rats.

This study aimed to test the hypothesis that the tuberoinfundibular dopaminergic neurons of the arcuate nucleus and/or the lactotroph cells of the anterior pituitary gland are key targets for the programming effects of perinatal glucocorticoids (GCs). Dexamethasone was administered noninvasively to fetal or neonatal rats via the mothers' drinking water (1 mug/ml) on embryonic d 16-19 or neonatal d 1-7, and control animals received normal drinking water. At 68 d of age, the numbers of tyrosine hydroxylase-positive (TH+) cells in the arcuate nucleus and morphometric parameters of pituitary lactotrophs were analyzed. In control animals, striking sex differences in TH+ cell numbers, lactotroph cell size, and pituitary prolactin content were observed. Both pre- and neonatal GC treatment regimens were without effect in adult male rats, but in females, the overriding effect was to abolish the sex differences by reducing arcuate TH+ cell numbers (pre- and neonatal treatments) and reducing lactotroph cell size and pituitary prolactin content (prenatal treatment only) without changing lactotroph cell numbers. Changes in circulating prolactin levels represented a net effect of hypothalamic and pituitary alterations that exhibited independent critical windows of susceptibility to perinatal GC treatments. The dopaminergic neurons of the hypothalamic periventricular nucleus and the pituitary somatotroph populations were not significantly affected by either treatment regimen in either sex. These data show that the adult female hypothalamo-lactotroph axis is profoundly affected by perinatal exposure to GCs, which disrupts the tonic inhibitory tuberoinfundibular dopaminergic pathway and changes lactotroph morphology and prolactin levels in the pituitary and circulation. These findings provide new evidence for a long-term disruption in prolactin-dependent homeostasis in females, but not males, after inappropriate GC exposure in perinatal life.

Animals↗
PubMed2005

Altered mesencephalic dopaminergic populations in adulthood as a consequence of brief perinatal glucocorticoid exposure.

Early exposure to stressors is strongly associated with enduring effects on central nervous system function, but the mechanisms and neural substrates involved in this biological 'programming' are unclear. This study tested the hypothesis that inappropriate exposure to glucocorticoid stress hormones (GCs) during critical periods of development permanently alters the mesencephalic dopaminergic populations in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Using a rat model, the synthetic GC dexamethasone was added to the maternal drinking water during gestational days 16-19 or over the first week of postnatal life. In adulthood, the effects upon tyrosine hydroxylase immunopositive (TH+) cell numbers in the midbrain, and monoamine levels in the forebrain, of the adult offspring were assessed and compared with control offspring whose dams received normal drinking water. In the VTA, both prenatal and postnatal dexamethasone treatment increased TH+ cell numbers by approximately 50% in males and females. Although prenatal dexamethasone treatment also increased TH+ cell numbers in the SNc by 40-50% in males and females, postnatal treatment affected females only by increasing TH+ cell numbers by approximately 30%. In comparison, similar changes were not detected in the monoamine levels of the dorsolateral striatum, nucleus accumbens or infralimbic cortex of either males or females, which is a feature likely to reflect adaptive changes in these pathways. These studies demonstrate that the survival or phenotypic expression of VTA and SNc dopaminergic neurones is profoundly influenced by brief perinatal exposure to GCs at times when endogenous levels are normally low. These findings are the first to demonstrate permanent changes in the cytoarchitecture within midbrain dopamine nuclei after perinatal exposure to stress hormones and implicate altered functionality. Thus, they have significance for the increasing use of GCs in perinatal medicine and indicate potential mechanisms whereby perinatal distress may predispose to the development of a range of psychiatric conditions in later life.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Exotic pets.

Explore the source record for details and available documents.

Animals↗
PubMed1996

Side effects from influenza vaccination: differences between returned and random surveys.

Annually vaccinated Air National Guard members were surveyed by return of questionnaire in 1991 (20.5%) and in 1992 by random phone survey (23.5%). By returned questionnaire the sample reported any side effects at the rate of 48.1%; by randomly telephoned sample a significantly lower rate, 37.7% (p < 0.02), was reported. An inverse relationship existed between age and return of the questionnaire, present only in males, despite an increased rate of reporting of side effects in the younger ages. Females reported a significantly higher rate of side effects than males by return of questionnaire in all age groups and for the sample as a whole (p < 0.03). In the randomized survey the age effect disappeared, except for the tendency for the oldest group to report fewer side effects than the other age groups in their aggregate (p < 0.07). The higher reporting rate for females was less apparent by random survey but remained as a trend (p = 0.08; odds ratio 1.398; 95% confidence interval = 0.776-4.049).

Adolescent↗
PubMed1992

Influence of vitamin B12 status on the inactivation of methionine synthase by nitrous oxide.

We have studied the influence of maternal serum B12 concentration on the inactivation of placental methionine synthase activity by nitrous oxide in an obstetric population. This group was known to include patients with a wide range of B12 values. Over 70% of patients were given nitrous oxide either for analgesia during labour or for delivery by Caesarean section, for periods ranging from a few minutes to 11 h. Patients undergoing normal delivery and Caesarean section under extradural anaesthesia served as controls. There was a highly significant relation between placental methionine synthase activity and duration of exposure to nitrous oxide. Inactivation was slower than that described for the liver, which may reflect the intermittent use. There was also a significant relation between maternal B12 and placental methionine synthase activity, but there was a wide scatter of results and the data were not thought to be predictive. There was evidence that inactivation by nitrous oxide was more rapid in patients with small concentrations of B12. We conclude that some patients with reduced serum concentrations of B12 may be at a disadvantage with nitrous oxide anaesthesia.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1991

Biochemical and behavioral characterization of a novel cholinergic agonist, SR 95639.

Selective M1 cholinergic agonists may be useful in treating dementias due to cholinergic hypofunction. SR 95639 has recently been described as such a compound. We found the compound to have affinity for M1 sites (Ki = 2.1 microM) which was approximately 3-fold higher than its affinity for M2 sites. Functional partial agonism was suggested by an inconsistent increase in phosphoinositide (PI) turnover in rat hippocampal slices, combined with blockade of carbachol-stimulated PI turnover. In vivo M2-mediated effects were absent. Scopolamine-induced hyperactivity was attenuated by SR 95639 and scopolamine-impaired inhibitory avoidance and radial maze performance were improved. The compound appears to be a weakly selective M1 partial agonist with potential advantages over existing compounds.

Animals↗
PubMed1990

Aspects of protein metabolism after elective surgery in patients receiving constant nutritional support.

1. The present study was designed in an attempt to resolve conflicting views currently in the literature relating to the effect of surgery on various aspects of protein metabolism. 2. Sequential post-operative (2, 4 and 6 days) changes in whole-body protein turnover, forearm arteriovenous difference of plasma amino acids, glucose, lactate and free fatty acids, muscle concentration of free amino acids, RNA and protein, urinary nitrogen and 3-methylhistidine, plasma concentrations of insulin, cortisol and growth hormone, and resting metabolic rate, were measured in six patients undergoing uncomplicated elective total abdominal hysterectomy. 3. All patients received a constant daily diet, either orally or intravenously, based on 0.1 g of nitrogen/kg and an energy content of 1.1 times the resting metabolic rate for 7 days before and 6 days after surgery. 4. Whole-body protein turnover, synthesis and breakdown increased significantly 2 days after surgery (P less than 0.05) and returned towards pre-operative levels thereafter. 5. Forearm release of branched-chain amino acids and alanine, and efflux of glucose and lactate, were enhanced 4 days after surgery (P less than 0.05). Muscle glutamine and alanine concentrations were decreased on the fourth and sixth days after surgery (P less than 0.05). The RNA/protein ratio (indicating the capacity for protein synthesis) was unaltered. 6. A significant increase in urinary nitrogen and 3-methylhistidine was observed on days 3 and 4 after surgery (P less than 0.05). Thereafter, these parameters remained elevated, although failing to reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Atrial natriuretic peptide, altitude and acute mountain sickness.

1. To investigate the mechanisms of acute mountain sickness, 22 subjects travelled to 3100 m by road and the following day walked to 4300 m on Mount Kenya. Control measurements were made over 2 days at 1300 m before ascent and for 2 days after arrival at 4300 m. These included body weight, 24 h urine volume, 24 h sodium and potassium excretion, blood haemoglobin, packed cell volume, and symptom score for acute mountain sickness. In 15 subjects blood samples were taken for assay of plasma aldosterone and atrial natriuretic peptide. 2. Altitude and the exercise in ascent resulted in a marked decrease in 24 h urine volume and sodium excretion. Aldosterone levels were elevated on the first day and atrial natriuretic peptide levels were higher on both altitude days compared with control. 3. Acute mountain sickness symptom scores showed a significant negative correlation with 24 h urinary sodium excretion on the first altitude day. Aldosterone levels tended to be lowest in subjects with low symptom scores and higher sodium excretion. No correlation was found between changes in haemoglobin concentration, packed cell volume, 24 h urine volume or body weight and acute mountain sickness symptom score. 4. Atrial natriuretic peptide levels at low altitude showed a significant inverse correlation with acute mountain sickness symptom scores on ascent.

Acute Disease↗