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Journal of Nuclear Medicine : Official... Jul 1986Thiouracil and various derivatives are selectively incorporated into the melanin pigment of melanomas during biosynthesis by serving as false melanin precursors. Using... (Comparative Study)
Comparative Study
Thiouracil and various derivatives are selectively incorporated into the melanin pigment of melanomas during biosynthesis by serving as false melanin precursors. Using the transplantable Harding-Passey melanoma carried in BALB/c mice, we have extended our previous studies with sulfur-35 (35S) thiouracil. The persistence of high levels of [35S]thiouracil in tumor for periods of up to 2 wk has been demonstrated; during this time the drug content in normal tissues returned to near background levels. The variety of iodine isotopes available makes iodothiouracil a particularly promising melanoma-localizing agent. Tumor uptake and biodistribution of [35S]thiouracil and iodothiouracil (both iodine-127 (127I) and iodine-125 (125I) labeled) have been compared and were found to be essentially the same. The selectivity of [125I]thiouracil for melanoma has been qualitatively demonstrated by autoradiography of whole-body sections and quantitated by analysis of tumor and selected tissues. Iodothiouracil was also shown to localize in remote secondary metastases using a metastatic variant of the Harding-Passey melanoma currently being developed in our laboratory. These studies confirm the melanoma localizing capabilities of an iodinated thiouracil, and therefore the potential of using iodinated thiouracil derivatives for diagnosis and therapy of melanotic melanomas.
Topics: Animals; Female; Iodine Radioisotopes; Melanoma; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Radionuclide Imaging; Sulfur Radioisotopes; Thiouracil; Tissue Distribution
PubMed: 3723191
DOI: No ID Found -
Medicine Jul 2021The aim of this study was to evaluate the efficiency and safety of methimazole (MMI) and propylthiouracil (PTU) in the treatment of hyperthyroidism.
PURPOSE
The aim of this study was to evaluate the efficiency and safety of methimazole (MMI) and propylthiouracil (PTU) in the treatment of hyperthyroidism.
METHODS
Articles were searched through the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and QVIP. The primary outcomes were clinical efficacy and thyroid hormone levels in MMI and PTU groups. The secondary outcomes were liver function indexes and adverse reactions in MMI and PTU groups. Results were expressed as weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs). The Begg test was applied to assess the publication bias.
RESULTS
Totally, 16 randomized controlled trials were retained in this meta-analysis with 973 patients receiving MMI and 933 receiving PTU. The levels of triiodothyronine (T3) (WMD = -1.321, 95% CI: -2.271 to -0.372, P = .006), thyroxine (T4) (WMD = -37.311, 95% CI: -61.012 to -13.610, P = .002), Free T3 (FT3) (WMD = -1.388, 95% CI: -2.543 to -0.233, P = .019), Free T4 (FT4) (WMD = -3.613, 95% CI: -5.972 to -1.255, P = .003), and the risk of liver function damage (OR = 0.208, 95% CI: 0.146-0.296, P < .001) in the MMI group were lower than those in the PTU group. The thyroid-stimulating hormone level (WMD = 0.787, 95% CI: 0.380-1.194, P < .001) and the risk of hypothyroidism (OR = 2.738, 95% CI: 1.444-5.193, P = .002) were higher in the MMI group than those in the PTU group.
CONCLUSIONS
Although MMI might have higher risk of hypothyroidism than PTU, the efficacy of MMI may be better than PTU in patients with hyperthyroidism regarding reducing T3, T4, FT3, and FT4 levels, decreasing the risk of liver function damage and increasing the level of thyroid-stimulating hormone.
REGISTER NUMBER
osf.io/ds637 (https://osf.io/search/).
Topics: Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Randomized Controlled Trials as Topic
PubMed: 34397700
DOI: 10.1097/MD.0000000000026707 -
Medicine Jul 2019Propylthiouracil (PTU) is a common antithyroid drug which can treat hyperthyroidism effectively. PTU is, however, associated to multiple adverse effects. In rare case,...
RATIONALE
Propylthiouracil (PTU) is a common antithyroid drug which can treat hyperthyroidism effectively. PTU is, however, associated to multiple adverse effects. In rare case, PTU can cause interstitial pneumonia.
PATIENT CONCERNS
A 40-year-old woman presented with dyspnea and was diagnosed with pulmonary infection at the first time. After the treatment with moxifloxacin, her symptoms still got worse.
DIAGNOSIS
The lung tissues biopsy confirmed the diagnosis of organizing pneumonia (OP) and the administration of PTU suggested the diagnosis of PTU-induced OP.
INTERVENTION
Withdrawal of PTU and the administration of methylprednisolone.
OUTCOMES
The patient's symptoms relieved significantly 1 month later and lung computed tomography (CT) scan also demonstrated significant reduction of lung lesions.
LESSONS
Here we report the first case of histologically confirmed OP induced by PTU and conduct a literature review of the cases of PTU-induced interstitial pneumonia. The awareness of PTU-induced OP can help physicians reduce the possibility of misdiagnosis.
Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Lung Diseases, Interstitial; Propylthiouracil; Tomography, X-Ray Computed
PubMed: 31277157
DOI: 10.1097/MD.0000000000016284 -
Endocrine Journal Apr 2019Methimazole (MMI) and propylthiouracil (PTU) are commonly used for the treatment of Graves' disease. They share similar inhibitory effects on thyroid hormone...
Methimazole (MMI) and propylthiouracil (PTU) are commonly used for the treatment of Graves' disease. They share similar inhibitory effects on thyroid hormone biosynthesis by interfering with thyroid peroxidase (TPO)-mediated oxidation and organification of iodine. However, their potential effects on other thyroid functional molecules have not been explored in depth. To identify novel effects of MMI and PTU, DNA microarray analysis, real-time PCR, Western blotting, immunofluorescence staining and confocal laser scanning microscopy were performed using FRTL-5 rat thyroid cells. DNA microarray analysis indicated that both MMI and PTU suppress iodotyrosine deiodinase 1 (Iyd, Dehal1) mRNA levels. Further studies revealed that Dehal1 mRNA levels was stimulated by TSH, insulin and serum, while it was suppressed by iodine and a follicular concentration of thyroglobulin. MMI and PTU significantly suppressed Dehal1 expression induced by TSH, insulin and serum. On the other hand, although MMI suppressed Dehal1 expression in the absence of TSH, PTU only weakly suppressed Dehal1 without TSH. These results suggest that PTU and MMI may use different mechanisms to regulate Dehal1 expression, and TSH may play essential and differential roles in mediating PTU and MMI signals in thyrocytes. The drugs also inhibited re-distribution of Dehal1 protein into newly formed lysosomes following thyroglobulin endocytosis. These findings imply complex and multifaceted regulation of Dehal1 in the thyroid and suggest that MMI and PTU modulate Dehal1 expression and distribution of the protein in thyrocytes to exert their effect.
Topics: Animals; Antithyroid Agents; Cell Line; Insulin; Iodide Peroxidase; Methimazole; Propylthiouracil; Rats; Thyroid Epithelial Cells; Thyrotropin
PubMed: 30814441
DOI: 10.1507/endocrj.EJ18-0380 -
Scientific Reports Aug 2019Ruthenium(II) complexes with 6-methyl-2-thiouracil cis-[Ru(6m2tu)(PPh)] (1) and [Ru(6m2tu)(dppb)] (2) (where PPhtriphenylphosphine;...
Ruthenium(II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK/p38 pathways in human acute promyelocytic leukemia cells.
Ruthenium(II) complexes with 6-methyl-2-thiouracil cis-[Ru(6m2tu)(PPh)] (1) and [Ru(6m2tu)(dppb)] (2) (where PPhtriphenylphosphine; dppb = 1,4-bis(diphenylphosphino)butane; and 6m2tu = 6-methyl-2-thiouracil) are potent cytotoxic agents and able to bind DNA. The aim of this study was to evaluate in vitro cellular underlying mechanism and in vivo effectiveness of these ruthenium(II) complexes in human acute promyelocytic leukemia HL-60 cells. Both complexes displayed potent and selective cytotoxicity in myeloid leukemia cell lines, and were detected into HL-60 cells. Reduction of the cell proliferation and augmented phosphatidylserine externalization, caspase-3, -8 and -9 activation and loss of mitochondrial transmembrane potential were observed in HL-60 cells treated with both complexes. Cotreatment with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, reduced Ru(II) complexes-induced apoptosis. In addition, both metal complexes induced phosphorylation of histone H2AX (S139), JNK2 (T183/Y185) and p38α (T180/Y182), and cotreatment with JNK/SAPK and p38 MAPK inhibitors reduced complexes-induced apoptosis, indicating DNA double-strand break and activation of caspase-mediated apoptosis through JNK/p38 pathways. Complex 1 also reduced HL-60 cell growth in xenograft model. Overall, the outcome indicated the ruthenium(II) complexes with 6-methyl-2-thiouracil as a novel promising antileukemic drug candidates.
Topics: Animals; Apoptosis; Caspases; Cell Proliferation; Coordination Complexes; DNA Breaks, Double-Stranded; Female; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute; MAP Kinase Signaling System; Mice; Phosphorylation; Ruthenium; Thiouracil; Xenograft Model Antitumor Assays
PubMed: 31391500
DOI: 10.1038/s41598-019-47914-x -
Molecules (Basel, Switzerland) Apr 2017The synthesis of novel modified nucleotides and their incorporation into DNA sequences opens many possibilities to change the chemical properties of oligonucleotides...
The synthesis of novel modified nucleotides and their incorporation into DNA sequences opens many possibilities to change the chemical properties of oligonucleotides (ONs), and, therefore, broaden the field of practical applications of modified DNA. The chemical synthesis of nucleotide derivatives, including ones bearing thio-, hydrazino-, cyano- and carboxy groups as well as 2-pyridone nucleobase-containing nucleotides was carried out. The prepared compounds were tested as substrates of terminal deoxynucleotidyl transferase (TdT). The nucleotides containing ⁴-aminocytosine, 4-thiouracil as well as 2-pyridone, 4-chloro- and 4-bromo-2-pyridone as a nucleobase were accepted by TdT, thus allowing enzymatic synthesis of 3'-terminally modified ONs. The successful UV-induced cross-linking of 4-thiouracil-containing ONs to TdT was carried out. Enzymatic post-synthetic 3'-modification of ONs with various photo- and chemically-reactive groups opens novel possibilities for future applications, especially in analysis of the mechanisms of polymerases and the development of photo-labels, sensors, and self-assembling structures.
Topics: Cytosine; DNA Nucleotidylexotransferase; Genetic Engineering; Mutagenesis; Oligonucleotides; Substrate Specificity; Thiouracil
PubMed: 28441732
DOI: 10.3390/molecules22040672 -
International Journal of Molecular... Oct 2022Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the...
Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the thiouracil-based dihydroindeno pyrido pyrimidines against topoisomerase I and II. The IC50 of other cell lines including the normal human lung cell line W138, lung cancer cell line, A549, breast cancer cell line, MCF-7, cervical cancer, HeLa, and liver cancer cell line HepG2 was evaluated using biochemical methods. The global reactivity descriptors and physicochemical parameters were computed, showing good agreement with the Lipinski and Veber's rules of the drug criteria. The molecular docking study of the ligands with the topoisomerase protein provides the binding sites, binding energies, and deactivation constant for the inhibition pocket. Various biochemical methods were used to evaluate the IC50 of the cell lines. The QSAR model was developed for colorectal cell line HCT as a case study. Four QSAR statistical models were predicted between the IC50 of the colorectal cell line HCT to correlate the anticancer activity and the computed physicochemical and quantum chemical global reactivity descriptors. The predictive power of the models indicates a good correlation between the observed and the predicted activity.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; Drug Screening Assays, Antitumor; Humans; Molecular Docking Simulation; Molecular Structure; Pyrimidines; Quantitative Structure-Activity Relationship; Structure-Activity Relationship; Thiouracil
PubMed: 36233102
DOI: 10.3390/ijms231911799 -
Poultry Science May 1975The effect of two levels each of methionine (0.0 and 0.07 percent), thiouracil (0.0 and 0.05 percent), dienestrol diacetate (0.0 and 0.007 percent), and thyroactive...
The effect of two levels each of methionine (0.0 and 0.07 percent), thiouracil (0.0 and 0.05 percent), dienestrol diacetate (0.0 and 0.007 percent), and thyroactive casein (0.0 and 0.0125 percent) on the performancy, organ changes, and liver composition in 640 pullets of two strains was studied in a 24 factorial arrangement of treatments. Egg production, egg characteristics, feed conversion, organ weights, and liver composition were parameters measured. Supplemental methionine increased the phosphorus content of liver fat in strain A, but other parameters in the two strains were mot affected by the increase in dietary methionine. The thiouracil increased weight grains, gram of fat per total liver, percent of liver fat, thyroid weight, and heart weight but decreased the phosphorus content of liver fat. Nine typical cases of fatty liver syndrome with large liver hematomas occurred in the thiouracil treated birds and one case occurred in an untreated pullet. Dienestrol diacetate did not affect egg production, egg characteristics, organ weights, and liver composition in the two strains. Thyroprotein decreased weight gain, abdominal fat, liver weight. liver fat, thyroid weight, and percent red cells, but decreased percent blood sports in eggs and adjusted weights of the kidney and heart in both strains.
Topics: Adipose Tissue; Animal Feed; Animals; Caseins; Chickens; Dienestrol; Eggs; Fatty Liver; Female; Hematoma; Hemorrhage; Iodoproteins; Lipid Metabolism; Liver; Liver Diseases; Methionine; Phenols; Phosphorus; Poultry Diseases; Syndrome; Thiouracil
PubMed: 1153373
DOI: 10.3382/ps.0540715 -
Nutrients May 2020The innate liking of fats may be due to one or more orosensory, post-ingestive, and metabolic signals; however, individuals differ in their preference for fat in meat.... (Comparative Study)
Comparative Study
The innate liking of fats may be due to one or more orosensory, post-ingestive, and metabolic signals; however, individuals differ in their preference for fat in meat. One of the variables that mainly impacts eating behaviors and thus should be carefully analyzed is sex/gender, and while sex (female/male, in a binary approximation) refers only to biological characteristics, gender (woman/man, in a binary approximation) refers to cultural attitudes and behavior. This study aimed at exploring the role of gender, age, taste responsiveness (measured as sensitivity to the bitterness of 6-n-propylthiouracil (PROP)), personality traits, attitudes, and liking of and familiarity with meat on the choice of fat-rich meat products in 1208 women and men aged 18-66. Both a between- and a within-gender approach were adopted. Results showed that gender had a major impact on liking of and familiarity with meat and choice for fat-rich meat compared to age. A lower liking meat in general was found in women, independently of fat content. Women also reported a lower familiarity than men with fatty meat and cold meat and a lower choice of fat-rich meat. Genders differed in the influence of personality and attitudes about fat-rich meat choice. In both genders, the choice of meat higher in fat was associated with liking cold and fatty meat and with age and negatively with liking low-fat meat. Women were in general more interested in health than men, and this may explain the main difference in the choice of fat-rich meat between genders. However, when we look at each gender separately, general health interest was significantly correlated with a lower choice of fat-rich meat only in men. In addition, in men food neophobia was negatively correlated with choice of fat-rich meat. In women, the emotional dimension was found to play an important role, with sensitivity to disgust that was negatively associated with fat-rich meat choice and emotional eating that was positively associated with it. Thanks to the large sample and the gender-sensitive approach adopted, this study showed that different factors affect choice of fat-rich meat by gender, in addition to liking of and familiarity with fat-rich and cold meat and age. This suggests that strategies personalized by gender to reinforce or activate barriers to this type of consumption may be more effective at reducing fat intake, promoting the consumption of meat lower in fat.
Topics: Adult; Age Factors; Attitude to Health; Dietary Fats; Feeding Behavior; Female; Food Preferences; Humans; Male; Meat; Middle Aged; Personality; Propylthiouracil; Psychological Tests; Sex Factors; Taste
PubMed: 32403419
DOI: 10.3390/nu12051374 -
PloS One 2018In the European Union, the use of thyreostats for animal fattening purposes has been banned and monitoring plans have been established to detect potential abuse....
In the European Union, the use of thyreostats for animal fattening purposes has been banned and monitoring plans have been established to detect potential abuse. However, this is not always straightforward as thyreostats such as thiouracil may also have a semi-endogenous origin. Therefore, this study aimed at defining urinary metabolites, which may aid in defining the origin of detected thiouracil. Hereto, a parallel-like randomized in vivo study was conducted in which calves (n = 8) and cows (n = 8) were subjected to either a control treatment, rapeseed-enriched diet to induce semi-endogenous formation, or thiouracil treatment. Urine samples (n = 330) were assessed through metabolic fingerprinting, employing liquid-chromatography and Q-ExactiveTM Orbitrap mass spectrometry. Urinary fingerprints comprised up to 40,000 features whereby multivariate discriminant analysis was able to point out significant metabolome differences between treatments (Q2(Y) ≥ 0.873). Using the validated models, a total of twelve metabolites (including thiouracil) were assigned marker potential. Combining these markers into age-dependent biomarker panels rendered a tool by which sample classification could be improved in comparison with thiouracil-based thresholds, and this during on-going thiouracil treatment (specificities ≥ 95.2% and sensitivities ≥ 85.7%), post-treatment (sensitivities ≥ 80% for ≥ 24 h after last administration), and simulated low-dose thiouracil treatment (exogenous thiouracil below 30 ng μL-1). Moreover, the metabolic relevance of revealed markers was supported by the suggested identities, for which a structural link with thiouracil could be determined in most cases. The proposed biomarker panels may contribute to a more justified decision-making in monitoring thiouracil abuse.
Topics: Animals; Biomarkers; Cattle; Diet; Thiouracil; Urinalysis
PubMed: 29649241
DOI: 10.1371/journal.pone.0195351