An improved method for the biological assay of thyrocalcitonin.
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Biomedical subjects
Publications and source records attributed to C W Cooper.
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Heparin has been chemically combined with a number of plastic surfaces rendering them nonthrombogenic as judged by Lee-White coagulation tests in vitro with human blood. Addition of quaternary ammonium groups to the plastic permitted formation of insoluble complexes with heparin. These heparinized surfaces were essentially nonthrombogenic and adsorb blood proteins to a significantly smaller degree from dilute solution than do the unmodified plastic surfaces. The affinity of the formed blood elements for these modified surfaces is much less than for the unmodified surfaces.
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As part of an initial study we have attempted to ascertain whether lactating women exhibit high, clearly measurable levels of immunoreactive calcitonin (CT). Plasma levels of CT were measured in women who had been lactating for either a short time (less than 4 months) or a very long time (17-73 months). In 2 of 18 women lactating for only a short time CT levels were high and easily measured (greater than 200 pg/ml) while, in contrast, CT levels were undetectable (less than 60 pg/ml) in all of 16 nonlactating control subjects. In all six of the women studied who had been lactating for a long time, measurable levels of CT were observed, although provocative testing of women with measurable plasma CT using iv pentagastrin and calcium did not show a consistent pattern of CT secretory response. Thus, out of the total of 24 lactating women studied, one third were found to have measurable plasma levels of CT. The findings agree with studies in experimental animals which have indicated hypercalcitoninemia during lactation, but the factors responsible for the elevated CT levels during lactation remain to be elucidated.
A case-control study was undertaken to determine for the first time the specific aetiology of animal to human transmission of brucellosis in Saudi Arabia. Cases consisted of all patients with brucellosis attending the primary care clinic of the Riyadh Al-Kharj Hospital programme in central Saudi Arabia. A sample of individually matched controls was selected concurrently from patients attending the same clinic for unrelated problems. Cases and controls responded to a 48 item questionnaire on exposure to established risk factors for brucellosis. Greatest risk was found to be associated with indirect contact with animals (the consumption of unpasteurized dairy products), as opposed to direct contact with animals. When specific animal products were considered, greatest risk was associated with the consumption of milk and laban (buttermilk), as opposed to cheese or uncooked liver. When specific animal species were considered, greatest risk was associated with products derived from sheep and goats as opposed to camels and cattle. When direct contact with animals was considered, the study found a very high risk associated with assisting in animal parturition, but no significant risk associated with other direct (unspecified) animal contact.
Synthetic salmon calcitonin (sCT) given SC (30 MRC U/kg) or ICV (1.4 U, 300 ng) inhibited 24-hr food consumption in the rat by 50-100%. Furthermore, ICV doses of sCT ranging from 75 ng (0.35 U) to 300 ng (1.4 U) lowered both food and water intake in a dose-dependent manner. Use of various forms of CT give an apparent order of potency of salmon greater than porcine greater than or equal to human with sCT being at least 40 fold more potent than the mammalian forms. Measurement of food and water intake over a brief (30-90 min) period showed that ICV sCT was effective in reducing food and water consumption regardless of whether it had been given 1, 12, or 23 hr previously. Daily administration of sCT for 5 days caused marked suppression of food and water intake for 2 days; thereafter, consumption returned toward normal, becoming equivalent to vehicle injected controls by day 3 or 4 despite continued daily injections of sCT. The results show that CT can act centrally to modify certain types of behavior and are of special interest since CT-like peptides have been described in the pituitary and hypothalamus and since CT receptors have been reported in hypothalamic and other brain regions.
This paper contains the first demonstration of quantitative changes in the levels of calcitonin-like immunoreactivity in the pituitary. The concentration of calcitonin-like material in lean Zucker rats (?/+) was 0.42 +/- 0.09 ng/mg wet weight of pituitary. The pituitaries of obese rats (fa/fa) contained significantly greater levels (1.56 +/- 0.56 ng/mg wet weight). This 271% increase represents the first indication that pituitary calcitonin-like material may have a physiological role in genetically obese rats. Thyroidal calcitonin also elevated in the obese (111%). These large elevations in the calcitonin content of the glands of obese rats were not accompanied by significant elevations of calcitonin in the blood. This suggests that obese rats have problems with mechanisms for the release of calcitonin into the blood and might not be able to combat hypercalcemia as effectively as leans. However, this hypothesis remains to be tested.
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Thyrocalcitonin (TCT) is a 32 amino acid peptide hormone similar, but not identical, in structure from fish to man. Mammals produce the hormone in non-follicular thyroidal "C-cells" which can be identified visually using recently developed immunocytochemical methods. Although TCT exerts effects on the gut and kidney, bone seems to be the primary target tissue. The ability of TCT to restrict calcium fluxes from bone to blood and to inhibit bone resorption explains its utility for treating certain metabolic bone diseases, e.g. Paget's disease. The bone effects also account for the ability of TCT to combat a hypercalcemic challenge. Recent work suggests close relationships and a possible closed-loop feedback system between the gut and thyroid. In animals, gastrin is a potent TCT secretagogue; studies in man indicate that TCT, in turn, can effect gastric acid secretion and intestinal secretion of water and electrolytes. This gastrin-TCT relationship may help control levels of blood calcium during intestinal absorption of calcium following feeding. The ability of gastrin to stimulate TCT release has been applied clinically for the early diagnosis of medullary thyroid carcinoma (MTC), a C-cell tumor. Subclinical or questionable cases of MTC have been identified reliably using a simple, rapid provocative test involving pentagastrin injection and evaluation of blood samples by radioimmunoassay for elevated levels of TCT.
The presence of calcitonin gene-related peptide (CGRP) in both C-cells and nerve fibres around the thyroid blood vessels and follicles suggests that it may play a dual role, one of which may be in hormone secretion. Beta-CGRP injected intracerebroventricularly (icv) (1.875 nmol) caused a significant increase in the calcitonin CT) content of the C-cells in rat thyroid glands. The calcitonin content of the thyroids was determined by a radioimmunoassay using two antibodies and the results were expressed as ng CT/mg of fetal tissue. A significant rise in CT content of the thyroids occurred (5.5 +/- 0.5 n = 6), compared with the controls (3.5 +/- 0.1 n = 6). It is presumed that this change reflects an increase in the rate of secretion of CT in the thyroid glands of those rats so treated. The peptide might act on the central nervous system to stimulate the catecholamine outflow from the thyroid nerves and thereby increase the secretion rate of CT.