Methylthiouracil Research Articles

Comparison of the effects of various goitrogens on the biosynthesis of thyroid hormones in vitro.

ABSTRACT The effect of various goitrogens on in vitro biosynthesis of thyroid horhomes was studied. The compounds in decreasing order of relative activity to completely inhibit DIT formation were 1-methyl-2-mercaptoimidazole (MIA), thiouracil (TU); propylthiouracil PTU) and goitrin; thiourea and methylthiouracil (MTU). Those in decreasing order of relative activity to completely inhibit MIT formation were MIA; PTU, MTU, TU and thiourea; goitrin. Of the compounds tested MIA was thus the most potent inhibitor of the rat thyroid gland in vitro. The conversion of monoiodotyrosine to diiodotyrosine was more sensitive to every goitrogen than the iodination of tyrosine to form monoiodotyrosine. The modes of action of these antithyroid drugs seemed to be approximately the same, except for goitrin, which showed very weak inhibition of MIT formation. Progoitrin, the precursor of goitrin, did not seem to possess any antithyroid activity.

Observations on the effects of the administration of thiocyanate and thiouracil to sheep

Summary Failure to control the plasma level by renal secretion is the cause of the unpredictable toxicity of thiocyanate to sheep. High levels of methyl thiouracil given to the ewe do not produce goitres in the lambs as large as intermediate levels do. At these high levels iodide may enhance the goitrogenesis, while at lower levels it partially protects against goitre. The relation in time between the radioiodine concentration test and the duration and time of goitrogen administration has a great effect on the result. Previous suggestions that carrier iodide could increase the accumulation of radioiodine in the sheep by overcoming the goitrogenic effect of low levels of dietary thiocyanate are not confirmed. Regular ingestion of thiouracil by the pregnant ewe interferes with the rapid development of foetal thyroid activity found during the fourth month of pregnancy.

Hypothyroidism in the Sheep

The effect of the oral administration of methyl thiouracil at three dose rates to pregnant ewes has been studied. Observations were made on foetal skeletal growth and maturity, foetal and maternal thyroid iodine, plasma-protein-bound iodine (PBI), cholesterol, phospholipid, total esterified fatty acids, and calcium. A retardation of osseous growth and a significantly greater retardation of osseous maturity was found. The thyroid iodine concentration in both ewes and foetuses and the maternal total thyroid iodine in all treated groups were decreased but the foetal total thyroid iodine was reduced only in the two highest dose rates. Significant reduction in the foetal FBI was found only with the two highest dose rates and no significant changes were found in the maternal FBI concentration. Increases in all lipid fractions and a decrease in calcium concentration were found in the foetal plasma in the treated groups.

Death from aplastic anaemia following methyl thiouracil therapy.

Death from aplastic anaemia following methyl thiouracil therapy.

Energy metabolism and function of thyroid gland in vitro.

To obtain the information concerning the relation between the hormone synthetic function and metabolisms of thyroid gland, effects of some metabolic in hibitors upon oxidative, iodine and phosphorus metabolism of surviving beef and dog thyroid slices were studied with the uses of radioactive iodide (I131) and orthophosphate (P32). The main results obtained are as follows:1. Potassium cyanide (1×10-3M) shows remarkable inhibiting effect, in the same grade, upon oxygen consumption (“oxidation”), I131 uptake, iodine metabolism (“iodination”) and incorporation of radioactive phosphate into acid-soluble organic phosphate fraction (“phosphorylation”) of beef thyroid slice.2.2, 4-Dinitrophenol (DNP) in the concentrations of 1×10-5M, augments “oxidation”, while it inhibits “iodination” and “phosphorylation” of beef thyroid slice to a similar extent, showing an intimate relation between phosphorylation and iodination. In higher concentrations (5×10-5 to 1×10-4M) DNP decreases “oxidation” as well as “iodination” and “phosphorylation”.3. Methylthiouracil (MTU) in concentrations of 1×10-4 to 1×10-3M, has no effect on “oxidation” while it shows completely blocking effect on organic binding of iodine. However, “phosphorylation” is slightly inhibited by MTU (1×10-4M) and is inconsiderably increased in lower concentration (1×10-4M). In accordance with decrease of phosphorylation, iodination is also inhibited by MTU (1×10-3M).4. Glucose (100mg/dl), succinate (0.01M) and glutamate (0.01M) decrease “iodination” of dog thyroid slice despite increase of “oxidation” in the case of succinate. “Phosphorylation” of beef thyroid slice is not affected by the additions of glutamate and succinate. Glucose exerts an increasing effect of “phosphorylation”.5. The significance of the present results on the relation between energy metabolism and function of thyroid gland was discussed.

アルコール体内分解に及ぼすアドレナリン,アトロピン,ピロカルピン,TEA,アセトスルフアミン,甲状腺エキス,メチルチオウラシルの影響

アルコール体内分解に及ぼすアドレナリン,アトロピン,ピロカルピン,TEA,アセトスルフアミン,甲状腺エキス,メチルチオウラシルの影響

The maturation of behaviour in hypothyroidism and starvation

Summary o 1. Rats made hypothyroid during infancy, either by radio-thyroidectomy or by giving daily doses of methyl thiouracil, have been subjected to a series of tests designed to measure the maturation of innately organised behaviour and the capacity to respond adaptively to a new environment. Rats starved during infancy have been similarly treated. 2. Both the hypothyroid and starved rats matured more slowly than untreated littermates during the first 24 days of life, but the effect of thyroid deficiency was significantly more severe than that of starvation. Later in life, non-medicated cretinoid animals, although apparently becoming habituated more readily to a new situation than normal littermates, performed less well on an elevated spatial T-maze. 3. Rats starved during infancy but subsequently given ample food, and thyroxin-treated cretinoid rats, performed on the maze at least as well as did normal animals. 4. The significance of these results, and their contribution towards an explanation of the irreversibility of cerebral defects in many human cretins, is discussed.

The antithyroid action of para-aminosalicylic acid.

SUMMARY 1. Para-amino-salicylic acid (PAS sodium salt) given to rats under the experimental conditions described produces a fall of radio-iodine uptake to 10% of the control value at the end of 16 days. After 30 days this low level is unchanged. 2. Oxygen consumption falls gradually to 12% below the control value at the end of 30 days' treatment with PAS. 3. Thyroxine with PAS abolishes the fall in oxygen consumption and raises the radio-iodine uptake slightly above that given with PAS alone. 4. Methyl thiouracil with PAS does not depress the oxygen consumption level below that obtained with PAS alone. The radio-iodine uptake is raised slightly above that found with PAS. 5. After 15 weeks' administration of PAS radio-iodine uptake is more than double that of the control value. 6. The rise in radio-iodine uptake when thyroxine and methyl thiouracil are given with PAS and when PAS treatment is prolonged, is accompanied by structural changes in the thyroid gland indicative of an increased output of thyrotrophic hormone. 7. After 29 weeks' treatment with PAS signs of exhaustion of the thyroid gland appear. Complete degeneration of the follicular epithelium was observed in some animals at this time. 8. The structural changes in the gland are reversible even after 25 weeks' treatment with PAS at a dose level of 1 mg/g body weight/day.

Thyroid hypofunction and the development of the central nervous system.

METHYL thiouracil depresses the thyroid, and the brains of rats made cretinous with this drug grow proportionately less in length than they do in width or height1. Further results of this treatment are that myelination is retarded2 and that the pyramidal cells of the lamina ganglionaris of the sensori-motor cortex-are smaller and more closely packed than in normal animals1. The spaces between the cell bodies are occupied for the most part by neuroglia, blood vessels, axons and dendrites, and an attempt to find an explanation for the closer aggregation of the cell bodies in cretins has been made by analysing the rate of growth of each of these components.

The Administration of Methyl Thiouracil (“Obesil”) to Fattening Pigs

The Administration of Methyl Thiouracil (“Obesil”) to Fattening Pigs

Immunity and metabolic rate; the course of notoedric scabies in rats with different metabolic rates.

1. Two experiments are described investigating the effects of level of metabolism on (a) resistance to, and (b) recovery from, Notoedric scabies of rats. The progress and severity of the disease was measured by weekly counts of the number of lesions; the metabolic rate in some rats was raised by administration of iodinated casein and in others was depressed by methyl thiouracil.2. In normal rats, the initial severe phase of the disease was followed by a partial recovery with survival of a smaller population of parasites.3. This recovery process in established infestations was hastened by elevation and retarded by depression of the metabolic rate.4. Resistance to the development of severe disease was enhanced by elevation and reduced by depression of the basal metabolic rate.5. The level of the residual infestation, after the severe phase of the disease had passed, was also affected by the treatment, being decreased by the higher but increased by the lower metabolic rate.

FINAL RESULTS OF LONG‐TERM TREATMENT WITH METHYL THIOURACIL IN THYREOTOXICOSIS

Medical Journal of AustraliaVolume 2, Issue 2 p. 66-66 Correspondence FINAL RESULTS OF LONG-TERM TREATMENT WITH METHYL THIOURACIL IN THYREOTOXICOSIS First published: 01 July 1950 https://doi.org/10.5694/j.1326-5377.1950.tb80881.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume2, Issue2July 1950Pages 66-66 RelatedInformation

Problems Dealing with Preoperative Antithyroid Therapy

Based on the sensitizing effect of formaldehyde on the chemiluminescence (CL) reaction of propylthiouracil (PTU) and methylthiouracil (MTU) with acidic potassium permanganate and the combination technique of high-performance liquid chromatography (HPLC), a sensitive, selective and simple post-column CL detection method for determining PTU and MTU is described. The optimal conditions for the CL detection and HPLC separation were carried out. The linear ranges were 0.1–20 μg mL−1 for MTU and 0.1–10 μg mL−1 for PTU, the detection limits were 0.03 μg mL−1 for PTU, 0.03 μg mL−1 for MTU and the quantification limits were 0.1 μg mL−1 for PTU, 0.1 μg mL−1 for MTU. The method has been satisfactorily applied for the determination of MTU and PTU in human serum samples.

FINAL RESULTS OF LONG‐TERM THERAPY WITH METHYL THIOURACIL IN THYREOTOXICOSIS

Medical Journal of AustraliaVolume 1, Issue 23 p. 781-782 Correspondence FINAL RESULTS OF LONG-TERM THERAPY WITH METHYL THIOURACIL IN THYREOTOXICOSIS First published: 01 June 1950 https://doi.org/10.5694/j.1326-5377.1950.tb80739.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume1, Issue23June 1950Pages 781-782 RelatedInformation

FINAL RESULTS OF LONG‐TERM THERAPY WITH METHYL THIOURACIL IN THYREOTOXICOSIS

Medical Journal of AustraliaVolume 1, Issue 21 p. 712-713 Correspondence FINAL RESULTS OF LONG-TERM THERAPY WITH METHYL THIOURACIL IN THYREOTOXICOSIS First published: 01 May 1950 https://doi.org/10.5694/j.1326-5377.1950.tb80675.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume1, Issue21May 1950Pages 712-713 RelatedInformation

PINAL RESULTS OF LONG‐TERM THERAPY WITH METHYL THIOURACIL IN THYREOTOXICOSIS

Medical Journal of AustraliaVolume 1, Issue 15 p. 517-518 Correspondence PINAL RESULTS OF LONG-TERM THERAPY WITH METHYL THIOURACIL IN THYREOTOXICOSIS First published: 01 April 1950 https://doi.org/10.5694/j.1326-5377.1950.tb80484.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume1, Issue15April 1950Pages 517-518 RelatedInformation

FINAL RESULTS OF LONG‐TERM THERAPY WITH METHYL THIOURACIL IN THYREOTOXICOSIS

Medical Journal of AustraliaVolume 1, Issue 5 p. 139-143 Original Article FINAL RESULTS OF LONG-TERM THERAPY WITH METHYL THIOURACIL IN THYREOTOXICOSIS Hugh R. G. Poate, Hugh R. G. Poate SydneySearch for more papers by this author Hugh R. G. Poate, Hugh R. G. Poate SydneySearch for more papers by this author First published: 01 February 1950 https://doi.org/10.5694/j.1326-5377.1950.tb80115.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume1, Issue5February 1950Pages 139-143 RelatedInformation

Effect of Methyl Thiouracil and Thiouracil in Swine

Effect of Methyl Thiouracil and Thiouracil in Swine

Effects of Methyl Thiouracil in the Rations of Lambs and Aged Ewes

Effects of Methyl Thiouracil in the Rations of Lambs and Aged Ewes

Effect of Sulfa Preparations and Methyl Thiouracil on the Urinary Output of Vitamin C in the Rat

Summary.Sulfa preparations and methyl thiouracil deplete the stores of vitamin C in the organism. In prolonged use and in large doses they cause a lack of vitamin C which can be ascertained at least in laboratory experiments. Hence it is recommendable that vitamin C be administered in connection with the sulfa therapy especially as infectious cases themselves already cause an increased consumption of the vitamin.