Showing papers on "Propylthiouracil published in 1969"

Metabolism of 35S-labelled Antithyroid Drugs in Man

Abstract: Differences in the metabolic fate of antithyroid drugs influence the optimal frequency of administration and their therapeutic efficacy. 35S propylthiouracil differed from the 35S imidazoles (carbimazole and methimazole) in the more rapid absorption and excretion and the shorter biological half-life in the plasma of the former. Renal function may have a more important influence on the biological half-life of the drugs than thyroid status. Further work is required to determine the optimal frequency of administration for each compound.

The Use of Antithyroid Drugs in a Single Daily Dose: Treatment of Diffuse Toxic Goiter

Abstract: Fifty thyrotoxic patients were treated with a single daily dose of thionamide derivative. Forty-eight were treated with propylthiouracil and two with methimazole. Of 41 patients in whom a euthyroid state was induced with the usual multiple daily dose plan, 28 continued in remission for the remainder of their treatment when given the same amount of medication as a single dose before breakfast. In two others in whom a single daily dose was tried, the remission was maintained only after the dose was increased. Of 11 patients whose remission could not be maintained with the single daily dose, three were successfully managed when an equivalent amount of medication was given in divided doses at eight-hour intervals. Nine patients whose hyperthyroidism was less severe were successfully managed when given a single daily dose of propylthiouracil throughout the entire treatment period.

Action of target gland hormones on pituitary TSH rebound: validation of the threshold hypothesis of TSH secretion.

Abstract: Asynchronism was induced in production and release of TSH in young and old female rats by feeding propylthiouracil (PTU) in the diet (.1–.15%) for 32–450 days and withdrawing the goitrogen for 7–10 days before autopsy. PTU treatment consistently lowered TSH concentration in the adenohypophysis and increased plasma titers of the hormone (stasis tadpole method of assay). Withdrawal of the goitrogenic stimulus resulted in substantial reaccumulation of TSH in the pituitary to supranormal levels; plasma TSH levels usually decreased but still remained in the elevated range. Adrenal gland weight and corticosteroid content of plasma and adrenal were invariably decreased in the hypothyroid rat. No significant correlation was apparent between the status of pituitaryadrenocortical function and the shift in TSH secretion after cessation of PTU treatment. Dexamethasone administration, hemiadrenalectomyor placement of median eminence lesions in goitrous rats, all failed to inhibit pituitary TSHrebound following withdra...

Effects of Actinomycin D on the Thyroid1

Abstract: The effects of a single ip injection of actinomycin D (act D), 1 μg/g body weight, given 12–15 hr earlier, upon the iodide concentrating and organic binding function of the rat thyroid were studied. Administration of act D resulted in an increased thyroid serum concentration ratio for radioiodide (T/S [I–]) (blocked gland) and for pertechnetate (unblocked gland). There was no change in 10-min thyroid uptake of carrier-free 131I, glandular ATP content, thyroid/medium concentration ratio for 131I (T/M) or in the rate of efflux of glandular iodide in vitro. Act D did not increase the low T/S [I–] of thyroxinetreated rats or of the rats hypophysectomized 2 days earlier; however, act D increased the T/S [I–] of rats hypophysectomized 10 days earlier. Cycloheximide, unlike act D, depressed the incorporation into glandular protein of the 14C in injected amino acids, but did not raise T/S [I–]. The early T/S [I–]-lowering action of TSH was not blocked by act D. Act D pretreatment considerably impaired thyroid cap...

Hormone‐induced modifications of free tyrosine in the rat thyroid gland

Abstract: The concentrations of free tyrosine in liver, muscle, kidney and thyroid gland were determined in separate groups of rats maintained on a low iodine diet and treated with intraperitoneal injections of thyroxine (T 4), thyrotrophin (TSH) and TSH plus propylthiouracil (PTU). Groups of hypophysectomized rats also were given T 4. Significant changes in tissue tyrosine were generally confined to the thyroid gland. Animals treated with T 4 showed a decrease of mean thyroid tyrosine from 113·3 ± 17·9 ( S.D.) μg/g wet weight of gland to 76·2 ± 5·7 μg/g (P < 0·01). Although there was little change in content when TSH was given alone, a significant increase in tyrosine levels was observed when TSH plus PTU were administered (P < 0·01). In hypophysectomized rats thyroid tyrosine decreased and was further lowered (to 46·0 ± 3·1 μg/g; P < 0·05) by T 4 treatment. When tyrosine concentrations were expressed in relation to ribonucleic acid (RNA) or protein content of the assayed gland, all differences in tyrosine content became greater.

Factors Affecting the Synthesis of Transfer& by Rat Tissue Slices*

Abstract: From the Department of Physiology, The University of Western Australia, Nedlands, Australia 6009 SUMMARY The sites of transferrin synthesis and the factors affecting synthesis were investigated in the rat by measuring the incorporation of “C-leucine into transferrin, albumin, and yG-globulin precipitated with specific antisera. Twenty min- utes after the intravenous injection of 14C-leucine, the radio- activity was incorporated into microsomal transferrin of liver in much greater amounts than into that of other tissues. After incubation of tissue slices with “C-leucine in vifro, how- ever, radioactivity was incorporated into transferrin by liver, spleen, and bone marrow at about the same rates per unit per weight of tissue. Because of its greatest bulk, the liver again appeared to be by far the most important organ for transferrin synthesis. The incorporation of “C-leucine into transferrin and albu- min by liver slices was used as a measure of synthesis of the proteins. Transferrin synthesis was increased in rats with hemorrhagic iron deficiency anemia and in rats treated with thyroxine or exposed to reduced atmospheric pressure. Prior treatment of rats with 100 fig of actinomycin D per 100 g of body weight did not prevent the increase in transferrin synthesis produced by exposure to reduced atmospheric pressure. Decreased synthesis was found with liver from rats with transfusional polycythemia, fasted rats, and rats given propylthiouracil. Thyroxine and propylthiouracil treat- ment and fasting had similar effects on albumin synthesis, but the other treatments had no effect. Iron loading with iron-dextran and acute and chronic hemolytic anemia pro- duced with phenylhydrazine and methyl cellulose, respec- tively, resulted in little change in transferrin synthesis by liver slices. The concentration of transferrin in the plasma varies in highly predictable ways in humans at different stages of the life cycle and in certain diseases (I) and in laboratory animals under different experimental conditions. In the rat and rabbit, for instance, hemolytic and iron deficiency anemias, cobalt or thyroxine administ,ration, and exposure to reduced atmospheric * This work was supported by a grant from the Australian Re- search Grants Committee and by Grant 5 R05 TWO0212 from the Nat,ional Institutes of Health. pressure are accompanied by a rise in plasma transferrin level, while transfusional polycythemia, fasting, or treatment with propylthiouracil are associated with a fall in this level (2-5). It is probable that the changes in transferrin concentration are the result of alterations in the rate of synthesis of the protein, but direct experimental evidence on this is lacking. There is evidence for transferrin synthesis by liver, spleen, bone marrow, lymph nodes, thymus, and peritoneal macrophages in the rat (6, 7) and by some of these tissues in addition to the liver in mouse, rabbit, guinea pig, monkey, and humans (7-11). How- ever, the rate of transferrin synthesis in tissues other than the liver has not been measured. Hence, the relative importance of the other tissues for transferrin synthesis when compared wit.h the liver is uncertain. This work aims to determine the major sites of transferrin synthesis in the rat and then to study the effect of various factors, known to influence plasma transferrin concentration, on transferrin synthesis in vitro by tissue slices from the more important organs.

Effect of Propylthiouracil Feeding on Postnatal Development of Heart Rate in the Rat

Abstract: Postnatal change in heart rate of the rat has been studied by many investigators who report a relatively rapid increase in rate during the first 21 days after birth, followed by subsequent cardiac slowing approaching the adult level of 300-400 beats/minute (bpm) (Marcuse and Moore, 1943; Adolph, 1957; Wekstein, 1965). The ability of the heart to alter its rate in response to external stimuli changes during this period. Such procedures as pinprick and breathing of various concentrations of oxygen and CO2 produce a decrease in heart rate at birth, but at 6 days the same procedures result in either cardiac deceleration or acceleration (Adolph, 1965). The newborn rat apparently does not have the capacity to increase its heart rate in response to a number of different disturbances which cause cardiac acceleration in the adult. The administration of adrenergic blocking agents prevents the postnatal rise in heart rate. Newborn rats pretreated with reserpine exhibit a slight rise in heart rate during the first 6 days (Wekstein, 1965). Propranolol, another adrenergic blocker, as well as the ganglionic blocker pentolinium produce similar effects (Adolph, 1967).

Anatomic and Physiologic Effects of the Antithyroid Drug, Propylthiouracil, on Rats

Abstract: Administration of the antithyroid drug, propylthiouracil (PTU), to albino male rats at the dietary level of 0.1 % PTU is accompanied by a decrease in growth rate and a decrease in the oxygen consumption rate. After the initial administration of PTU, prolonged treatment with the drug did not further lower the oxygen consumption rate. The ratios of organ weight to body weight for the testes, stomach, thyroid, eyes, pituitary, and brain were found to be larger in the treated rats than in the untreated controls. The organ weight to body weight ratios of the spleen, liver, kidneys, and heart were smaller in the PTU treated rats than in the untreated controls examined. Propylthiouracil is known to affect various aspects of metabolism such as lowering the rate of oxygen consumpt~on and lowering the rate of increase of weight in young rats (Cook 1962). It has also been found that PTU treatment increases the ratio of organ weight to body weight of various organs including the thyroid, eye, and testes (Fregly and Hood, 1959). PTU treatment has been found to decrease the ratio of organ weight to body weight in the case of the heart and the kidneys (Fregly and Hood, 1959). The experiments reported here were conducted to determine whether prolonged administration of PTU resulted in a further decrease in the oxygen consumption rate, and to study the effects of PTU on the rat~o of organ weight to body weight on various organs not previously studied as well as those already studied.