Elimination profile of methylthiouracil in cows after oral administration.

In addition to methods for the determination of residues, there is an important need for knowledge of the fate and excretion of growth promoting substances in fattening animals. In court, often simple questions are asked, such as, over what period of time can the drug be detected?, is it possible to find residues after 2 months, etc. These questions can only be answered by conducting animal experiments. Data on excretion and distribution of thiouracils in cows are rather scarce. At the beginning of the 1980s, animal experiments with methylthiouracil (MTU) were carried out in the Laboratory of Chemical Analysis. These experiments showed that treatment of cows with MTU results in the rapid appearance of the drug in plasma, urine and milk, whereas MTU selectively accumulates in the thyroid gland. The results of these experiments were only published in media with limited access (thesis, abstracts) and also there has been a considerable improvement in data handling with computer programs in the last 15 years. This investigation reinterprets the 'old' analytical data from animal experiments using a pharmacokinetic software package.

Melatonin action on thyroid activity in the soft-shelled turtle, Lissemys punctata punctata.

Adult female turtles (Lissemys punctata punctata) were treated with pineal indoleamine melatonin (100 micrograms/100 g) or the antithyroid agent, methylthiouracil (100 micrograms/100 g) or melatonin together with methylthiouracil (100 micrograms of each drug/100 g) for 12 days. Melatonin alone inhibited thyroid activity as evidenced by reduction in the gland weight, follicular epithelial cell height, thyroid peroxidase, and plasma thyroxine levels. Methylthiouracil caused hyperplasia of the gland, although it inhibited thyroid activity and reduced thyroid peroxidase and plasma thyroxine levels. Melatonin together with methylthiouracil produced changes similar to those obtained with melatonin alone. The results indicate that melatonin probably exerts inhibitory effects influences on both thyrotropin release from the pituitary and the activity of the thyroid itself in turtles.

[Effectiveness of non-starch polysaccharide crylan in experimental hyperlipidemia]. / Effektivnost' nekrakhmal'nogo polisakharida krilana pri éksperimental'noi giperlipidemii.

In vitro experiments were shown that native ecologically pure non-starch polysaccharide crylan bind the bile acid. Crylan was found to decrease hyperlipidemia induced in rats by means of diet enriched with cholesterol and 6-methylthiouracil. This effect of crylan was more pronounced as compare with the action of native nonspecific enterosorbent polyfepan.

[Experimental substitution of carbimazole for Alkiron in the atherogenic diet]. / Pokus o náhradu alkironu carbimazolem v aterogenní diete.

Due to present unavailability of Alkiron the authors tried to substitute it by Carbimazole in atherogenic diet aimed at inducing advanced atherosclerosis in rats. Carbimazole proved to be entirely ineffective in this respect and thus the thiouracil derivatives cannot be substituted by it.

[An attempt to substitute carbimazole for Alkiron in an atherogenic diet]. / Pokus o náhradu alkironu carbimazolem v aterogenní diete.

Due to present unavailability of Alkiron the authors tried to substitute it by Carbimazole in atherogenic diet aimed at inducing advanced atherosclerosis in rats. Carbimazole proved to be entirely ineffective in this respect and thus the thiouracil derivatives cannot be substituted by it.

[Combined use of prodigiozan and methyluracil with immunosuppressive drugs in adjuvant arthritis in rats]. / Sochetannoe primenenie prodigiozana i metiluratsila s immunodepressantami pri ad'iuvantnom artrite u krys.

The effect of the combined use of prodigiozan (0.5 mg/kg bw) prodigiozan with immunosuppressants on the development of adjuvant arthritis was studied on rats. The drugs were given during the prearthritis period from the 1st to the 16th day after injection of complete Freund's adjuvant. It was shown that the combined use of prodigiozan and cyclophosphamide (5 mg/kg) induced significant inhibition of the arthritis development and extraarticular signs of the disease. The efficacy of the combination was higher than that of cyclophosphamide alone. Azathioprine (4 mg/kg/bw) produced no immunosuppressant effect and did not influence the inhibitory effect of prodigiozan on the development of the adjuvant disease. Prednisolone (1.6 mg/kg) either did not inhibit the arthritis development. However, it eliminated the prodigiozan effect. Methyluracil did not change the effect of the immunosuppressants on the articular syndrome. Still, it increased the number of nodular affections in the animals treated with cyclophosphamide and prednisolone. The data obtained show the possibility of prodigiozan combination with certain immunosuppressants in autoimmune affections and confirm the suggestion that the inhibitory effect of this drug is mediated through macrophages.

Weight increase of the thyroid gland as a tentative screening parameter to detect the illegal use of thyreostatic compounds in slaughter cattle.

A total of 45 normal or enlarged thyroid glands of adult slaughter cattle were weighed and analyzed by thin-layer chromatography for the presence of residues of the following thyreostatic compounds: thiouracil, methylthiouracil, propylthiouracil, phenylthiouracil, and methimazole. In 21 glands, mostly from imported animals, residues of methylthiouracil or methimazole were detected. These thyroids ranged in weight from 68-245 g (mean value 118 g). Glands in which no residues were found, varied in weight between 20 and 124 g (mean value 42 g). Taking an upper limit of 60 g as normal, 4 out of 22 were false-positive' with respect to the 5 thyreostatic compounds screened for, while no false-negative cases were scored. On the basis of these results the weight increase of the thyroid gland is proposed as a simple indirect parameter in the screening for the illegal use of thyreostatic compounds in slaughter cattle.

Estudo histológico do tecido de granulaçäo de feridas cutâneas de ratos hipotireoides e parotidectomizados / Histologic study of cutaneous wound's granulation tissue of hypothyroid and parotidectomized rats

Os autores procederam ao estudo histológico do processo de reparo de feridas cutâneas dorso-lombares de ratos submetidos à administraçäo diária de 25 mg de 6-propil-2-tiouracil e de ratos parotidectomizados. Os animais foram sacrificados, 4, 8 e 12 dias após a realizaçäo da ferida dorso-lombar tendo sido as peças obtidas por dissecaçäo incluídas em parafina pelo método rotineiro de uma vez processadas, foram coradas pela hematoxilinma-eosina, pelo tricrômico de Masson e pelo método de Van Gieson. A análise dos resultados, permitiu verificar que, em relaçäo aos animais controle, houve atraso na formaçäo e maturaçäo do tecido de granulaçäo dos animais tratados com 6-propil-2-tiouracil e antecipaçäo na formaçäo e maturaçäo do tecido de granulaçäo nos animais paratidectomizados

On the development of metastasizing tumors of the rat thyroid gland after combined administration of nitrosomethylurea and methylthiouracil.

Seventy-five female Wistar rats of 150 g each were given 3 X 40 mg/kg body weight nitrosomethylurea (NMU) and 4 weeks later until death (in the 9th-60th week) methylthiouracil (MTU), as a 0.1% solution in their drinking water. After 2 months, in the almost colloid-less thyroid gland individual foci appeared which consisted of sometimes colloid containing follicles with increased cytoplasmic and nuclear basophilia; they increased in number during the subsequent weeks and finally resulted in nodes with different morphologic structures. From the 16th week on there were tumors infiltrating the capsule, and after the 24th week there were angioinvasive carcinomas. Thirteen rats had developed lung metastasization after the 30th week. Cytology could only distinguish between the follicular carcinomas of low differentiation and the follicular adenomas. If these findings are applied to human pathology, one would have to reckon with adenomas which can develop their malignant characteristics without necessarily changing their histologic and cytologic appearance.

[Effects of T3, T4 and methyltiouracile short-term treatments on plasma and liver lipid levels in rats (author's transl)]. / Efectos de la administración a corto plazo de T3, T4 y metiltiouracilo sobre los niveles de lípidos en hígado y plasma de rata.

The effects of short-term administration of thyroid hormones (T3 and T4) and methyltiouracile (MTU) on liver and plasma lipid levels in female rats have been comparatively studied T3 increases the levels of all the studied liver lipids and decreases the plasma lipids. T4 produces smaller and even, in some cases (liver triglycerides and cholesterol esters), opposite effects. The administration of MTU produces, in general, opposite effects to T3 and T4.

[Possibilities of preventing cardiotoxic complications in chemotherapy with carminomycin]. / Vozmozhnosti preduprezhdeniia kardiotoksicheskikh oslozhnenii pri khimioterapii karminomitsinom.

Carminomycin chemotherapy of the patients with malignant tumors is often complicated with cardiopathy which is sometimes assymptomic and registered only electrocardiographycally. Chemotherapy on the background of reparative regeneration stimulators from the series of synthetic pyrrimidine derivatives, such as methyluracyl for oral use and a soluble salt of methyluracyl for parenteral administration significantly decreased the rate of the cardiotoxic complications and promoted a decrease in their level. The use of methyluracyl and its soluble salt did not decrease the therapeutic effect of carminomycin. Methyluracyl and its soluble salt may be recommended for prophylaxis of cardiotoxic complications in chemotherapy of malignant tumors with carminomycin.