Evaluation of a slimming group.
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Biomedical subjects
Publications and source records attributed to J Falconer.
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The increased production of cortisol by the fetal adrenal gland at term acts as the trigger for parturition in some species. The fetal pituitary controls fetal adrenal function. However, ACTH is only one of a family of closely related peptides which derive from a common precursor and we have shown that although ACTH is the dominant form in the adult pituitary, the expression of the "family trees' is altered in the fetus. In the sheep, it is large-molecular-weight precursors and, in the primate, the smaller peptides such as alpha-MSH, CLIP, beta-MSH and beta-endorphin that predominate in fetal life and which may be responsible for fetal adrenal function. It is still unclear what causes the developmental change in the ACTH "family tree'. Since it may result from a change in pituitary function - from the peptides of the pars intermedia, in the fetus, to those of pars anterior, in the adult - we have studied these two lobes separately in pituitaries taken from adult and fetal sheep and monkeys. Our preliminary results suggest that the change may occur in the neurointermediate lobe in the primate, but that in the sheep the developmental changes occur in the anterior lobe.
Somatomedin-like activity (SLA) was measured by bioassay in cord serum from infants of hypertensive mothers. Levels of SLA were lowest in "light for date' infants with birth weights below the 3rd centile, but did not correlate with birth weight, placental weight or maturity at delivery. Cord serum from female infants had significantly (P less than 0.001) higher levels of SLA than male infants. No differences in SLA were found between infants born after spontaneous labor or following induction.
Peripheral plasma concentrations of oxytocin, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM), progesterone and LH were determined at 3 hourly intervals during the oestrous cycle (n = 3) and in early pregnancy (n = 4) in sheep. The progesterone and LH concentrations showed that the cycling ewes were sampled during the periods of luteal regression (decreasing progesterone concentrations), the preovulatory gonadotrophin surge and the beginning of the next luteal phase (increasing progesterone concentrations). The pregnant ewes had basal LH concentrations and luteal phase concentrations of progesterone (greater than 1ng/ml after day 5 following mating) throughout the whole of the sampling period. Oxytocin concentrations in the non-pregnant ewes decreased around the time of luteal regression to reach low concentrations (mean concentrations of approximately 18pg/ml) during the preovulatory period and then increased after the preovulatory surge. PGFM concentrations exhibited a pulsatile pattern with increasing concentrations as progesterone levels fell. In the pregnant ewes oxytocin concentrations gradually fell until approximately 16 days post-mating (approximately 7-8pg/ml). The magnitude of the pulses in PGFM concentrations were also lower than in the cycling ewes. These results demonstrate that the increased concentrations of PGFM which are found during the period of luteal regression are not caused by increased peripheral concentrations of oxytocin.
Somatomedin-like activity (SLA) was measured in serial samples of amniotic fluid and maternal plasma from Rhesus monkeys (Macaca mulatta) using the porcine costal cartilage disc bioassay. Samples of both amniotic fluid and maternal plasma gave dose response curves which were parallel to the human plasma standard. Concentrations of SLA were consistently lower in amniotic fluid (0.42 +/- 0.02, mean +/- S.E.M., units/ml, n = 33) than in maternal plasma (0.60 +/- 0.03 units/ml, n = 31). No significant changes in concentrations of SLA with gestational age were found during the period studied (90-170 days of pregnancy). The presence of SLA in amniotic fluid is consistent with the possibility that somatomedin plays a role in the control of foetal or placental growth in the primate.
Variations to immunoreactive growth hormone (GH) and bioassayable somatomedin-like activity (SLA) were determined in the plasma of the domestic fowl. The plasma concentrations of SLA (potency relative to a pooled serum standard) and GH were both inversely age-related in growing cockerels (Thornber 909) between 3 and 20 weeks of age (SLA, r = 0.454; P less than 0.01, GH, r = 0.548; P less than 0.01) and directly related to each other (r = 0.54; P less than 0.01). In immature birds maintained on a photoperiod of 16 h light, 8 h darkness, plasma concentrations of SLA were highest during the first hour of darkness (1.19 +/- 0.18 units/ ml (u/ml) mean +/- S.E.M., n = 6) and significantly lower 1 h after dawn (0.78 +/- 0.07 u/ml n = 6). No diurnal variations in plasma concentrations of GH were observed. Deprivation of food in two strains of chickens (Thornber 909 and broiler) significantly reduced plasma concentrations of SLA in both strains and increased plasma concentrations of GH in the Thornber strain. Re-feeding fasted Thornber chickens caused the plasma concentrations of SLA and GH to return to normal within 24 h but had no effect in broilers. Deprivation of water, which also reduces food intake, for 12, 18 and 24 h markedly reduced plasma concentrations of SLA but had no effect on plasma GH concentration in Thornber cockerels.
Prostaglandins A1, A2, B2, E2, and F2 alpha inhibit glycosaminoglycan sulphation in pig costal cartilage discs above 0.1 micrometer M (5-25 ug/ml); no effects were found at concentrations down to 25 pg/ml. At concentrations above 1 microgram/ml (0.02 mM) prostaglandin E2 and F2 alpha inhibited cartilage DNA synthesis. However at 100 ng/ml (10 microM) this inhibition was again observed. The basal production of prostaglandins E2 and F2 alpha by the cartilage discs after incubation was below 15 pg/ml. The exact concentrations at which these inhibitory effects were observed varied from experiment (i.e. animal) to experiment.
Indomethacin, aspirin and hydrocortisone have been shown to inhibit glycosaminoglycan sulphation in pig costal cartilage discs. The doses at which inhibition was observed varied from pig to pig from 0.1 - 50 microgram/ml for indomethacin, 40 - 150 microgram/ml for aspirin and 0.5 - 1 mg/ml for hydrocortisone, doses which are achieved clinically in the treatment of joint diseases. In a minority of experiments a significant stimulation of glycosaminoglycan sulphation was observed at lower doses of indomethacin and hydrocortisone but not aspirin. THe results suggest that in rheumatoid arthritis but more especially osteoarthritis, treatment with these drugs should aim at finding the lowest doses which have a therapeutic effect. As importantly the clinician should always consider using lower doses just as much as higher doses when the first dose regimen is unsatisfactory.
Plasma samples were obtained from 8 conscious rhesus monkeys at 3-4 day intervals throughout the menstrual cycle. Oxytocin concentrations were significantly higher in mid-cycle (Days 10-11) than at Days 4-5 (P < 0.01) and Days 28-29 (P < 0.02, Wilcoxon signed rank test). No significant correlations between oxytocin and oestradiol or progesterone were found.
Somatomedin-like activity (SLA) was measured in plasma samples from cattle using the porcine costal cartilage disk bioassay. In 40-day-old pre-ruminant bull calves, SLA was highest in the plasma of eight Friesians (mean potency 0.97 +/- 0.06 (S.E.M.) units/ml), lowest in five Aberdeen Angus x Friesians (0.78 +/- P < 0.05) and intermediate in six Hereford x Friesians (9.89 +/- 0.09). Plasma levels of SLA were significantly (P < 0.01) lower in eight lactating Friesian (high-yielding) cows (0.53 +/- 0.04) than in five dry cows (0.76 +/- 0.06). Levels of SLA in the plasma of a further eight lactating Hereford x Friesian (low-yielding) cows (0.76 +/- 0.07) were similar to the levels in the plasma of the five dry dairy cows. Large diurnal changes in plasma SLA occurred in lactating Hereford x Friesian and Friesian heifers. In three Hereford x Friesian heifers plasma levels of SLA were lowest at 19.00 h (0.39 +/- 0.07) and highest at 03.00 h (0.77 +/- 0.08). A similar pattern was present in plasma samples from three Friesian heifers; the lowest levels of SLA being at 21.00 h (0.37 +/- 0.07) and the highest at 05.00 h (0.61 +/- 0.13). Throughout the period of 24 h the overall mean levels of SLA were significantly (P < 0.01) higher in the plasma samples from the three Hereford x Friesian heifers (0.6 +/- 0.01) than in the samples from the three Friesian heifers (0.49 +/- 0.02 units/ml).
Plasma samples from pregnant ewes and their foetuses during the last quarter of gestation were assayed for somatomedin-like activity (SLA) using the procine costal cartilage assay. In maternal plasma, the mean potency (compared with pooled serum from six sheep) was 0.84 +/- 0.05 (S.E.M.) units/ml (n = 15). Somatomedin-like activity in the plasma of five control foetuses (0.91 +/- 0.1 units/ml) was similar to the maternal levels and did not change with gestational age. After foetal hypophysectomy the SLA in foetal plasma (0.37 +/- 0.05 units/ml, n = 4) was significantly less than in control animals. In two nephrectomized foetuses, the mean SLA in plasma (0.08 and 0.51 units/ml respectively) was less than in control animals. Retardation of intra-uterine foetal growth was induced by removal of endometrial caruncles before pregnancy in four sheep. The SLA in plasma from these foetuses was 0.38 +/- 0.05 units/ml (P less than 0.01 v. control animals). The results suggest that SLA in the foetus may be important in the regulation of foetal growth, but they also indicate that factors other than growth hormone may be important in the control of SLA in foetal plasma.
Somatomedin-like activity was measured in the plasma of growing lambs using the porcine costal cartilage disk assay. Plasma concentrations were found to be high initially at 2 days of age (mean potency 1.02 plus or minus 0.13 (SEM) units/ml, n = 4) declined significantly by 8 days of age (mean potency 0.65 plus or minus 0.04 units/ml, n = 5, P less than 0.01, analysis of variance). Thereafter somatomedin-like activity declined slowly to reach its lowest concentration at 146 days of age (mean potency 0.61 plus or minus 0.04 units/ml, n = 5) then it rose slowly until 288 days of age (mean potency 0.61 +/- 0.04 units/ml, n = 5. These changes in somatomedin-like activity were accompanied by high initial plasma concentrations of growth hormone (24.8 plus or minus 4.8 ng/ml, n = 5) which declined under 188 days of age (2.8 plus or minus 0.04 ng/ml, n- 5) and then rose slightly until 288 days of age (13.8 plus or minus 9 ng/ml, n=5). Plasma prolactin concentrations showed a different pattern being low initially (47.8 plus or minus 8.7 ng/ml, n = 5) rising until 146 days of age (203 plus or minus 16 ng/ml, n = 5) and then declining to low value for the rest of the experiment. The relationships between these factors is not clear but somatomedin-like activity shows a pattern in the lamb which is highest when growth is faster (i.e. in the young lamb).
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