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Dong, Mendeley S Data) - One of the best experts on this subject based on the ideXlab platform.
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Supplementary data for Xiao-Luo-Wan treats Propylthiouracil-induced goiter with hypothyroidism in rats through the PI3K-AKT/RAS pathways based on UPLC/MS and network pharmacology
2021Co-Authors: Dong, Mendeley S Data)Abstract:Supplementary data for Xiao-Luo-Wan treats Propylthiouracil-induced goiter with hypothyroidism in rats through the PI3K-AKT/RAS pathways based on UPLC/MS and network pharmacolog
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Supplementary data for Xiao-Luo-Wan treats Propylthiouracil-induced goiter with hypothyroidism in rats through the PI3K-AKT/RAS pathways based on UPLC/MS and network pharmacology
2021Co-Authors: Dong, Mendeley S Data)Abstract:Supplementary data for Xiao-Luo-Wan treats Propylthiouracil-induced goiter with hypothyroidism in rats through the PI3K-AKT/RAS pathways based on UPLC/MS and network pharmacologyTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV
Scott A Rivkees - One of the best experts on this subject based on the ideXlab platform.
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evaluation of developmental toxicity of Propylthiouracil and methimazole
Birth Defects Research Part B-developmental and Reproductive Toxicology, 2014Co-Authors: Murali K Mallela, Carmen J Booth, Christopher C Wendler, Marie Strobl, Ryan R Poulsen, Scott A RivkeesAbstract:BACKGROUND Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs. METHODS We evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague-Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20. RESULTS In mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown-rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed. CONCLUSION We did not observe either gross external malformations or histopathological malformations in mice or rats treated long-term with high doses of PTU or MMI during pregnancy
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Propylthiouracil is teratogenic in murine embryos
PLOS ONE, 2012Co-Authors: Valeria C Benavides, Scott A Rivkees, Murali K Mallela, Carmen J Booth, Christopher C WendlerAbstract:Background Hyperthyroidism during pregnancy is treated with the antithyroid drugs (ATD) Propylthiouracil (PTU) and methimazole (MMI). PTU currently is recommended as the drug of choice during early pregnancy. Yet, despite widespread ATD use in pregnancy, formal studies of ATD teratogenic effects have not been performed. Methods We examined the teratogenic effects of PTU and MMI during embryogenesis in mice. To span different periods of embryogenesis, dams were treated with compounds or vehicle daily from embryonic day (E) 7.5 to 9.5 or from E3.5 to E7.5. Embryos were examined for gross malformations at E10.5 or E18.5 followed by histological and micro-CT analysis. Influences of PTU on gene expression levels were examined by RNA microarray analysis. Results When dams were treated from E7.5 to E9.5 with PTU, neural tube and cardiac abnormalities were observed at E10.5. Cranial neural tube defects were significantly more common among the PTU-exposed embryos than those exposed to MMI or vehicle. Blood in the pericardial sac, which is a feature indicative of abnormal cardiac function and/or abnormal vasculature, was observed more frequently in PTU-treated than MMI-treated or vehicle-treated embryos. Following PTU treatment, a total of 134 differentially expressed genes were identified. Disrupted genetic pathways were those associated with cytoskeleton remodeling and keratin filaments. At E 18.5, no gross malformations were evident in either ATD group, but the number of viable PTU embryos per dam at E18.5 was significantly lower from those at E10.5, indicating loss of malformed embryos. These data show that PTU exposure during embryogenesis is associated with delayed neural tube closure and cardiac abnormalities. In contrast, we did not observe structural or cardiac defects associated with MMI exposure except at the higher dose. We find that PTU exposure during embryogenesis is associated with fetal loss. These observations suggest that PTU has teratogenic potential.
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dissimilar hepatotoxicity profiles of Propylthiouracil and methimazole in children
The Journal of Clinical Endocrinology and Metabolism, 2010Co-Authors: Scott A Rivkees, Ana SzarfmanAbstract:Background: The antithyroid drugs Propylthiouracil and methimazole were introduced for clinical use about 60 yr ago and are estimated to be used in more than 6000 children and adolescents per year in the United States. Over the years that these medications have been used, reports of adverse events involving hepatotoxicity have appeared. To date, there has not been a systematic and comparative evaluation of the adverse events associated with antithyroid drug use. Objective: Our objective was to assess safety and hepatotoxicity profiles of Propylthiouracil and methimazole by age in the U.S. Food and Drug Administration’s Adverse Event Reporting System (AERS). Design: We used the multi-item gamma-Poisson shrinker (MGPS) data mining algorithm to analyze more than 40 yr of safety data in AERS. MGPS uses a Bayesian model to calculate adjusted observed to expected ratios [empiric Bayes geometric mean (EBGM) values] for every drug-adverse event combination in AERS, focusing on hepatotoxicity events. Results: MGPS...
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ending Propylthiouracil induced liver failure in children
The New England Journal of Medicine, 2009Co-Authors: Scott A Rivkees, Donald R MattisonAbstract:To the Editor: Graves' disease is treated with antithyroid drugs, radioactive iodine, or surgery.1,2 Propylthiouracil and methimazole are widely used in children as first-line therapy.1,2 Over the past 60 years of Propylthiouracil and methimazole use, reports of Propylthiouracil-related liver failure and death have accumulated.3–5 In contrast, this problem has not been reported with methimazole use in children.3,5 Several observations can be made on the basis of the medical literature, adverse event reports from the Food and Drug Administration (FDA), and extensive data presented at a workshop at the Eunice Kennedy Shriver National Institute of Child Health . . .
Qian Hongxi - One of the best experts on this subject based on the ideXlab platform.
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methimazole associated insulin autoimmune syndrome with hypoglycemic coma one case report
Chinese Journal of Diabetes, 2015Co-Authors: Qian HongxiAbstract:A female patient aged 48 years suffering from insulin autoimmune syndrome with hypoglycemiccoma was reported and analyzed.She was ill due to Graves' hyperthyroidism and took methimazole.The cause of hypoglycemiccoma was looked for.The determination of IAA was positive,and diagnosis of insulin autoimmune syndrome was established.The patient never received insulin treatment.During hypoglycemia,blood insulin levels were significantly elevated.Stopping methimazole and changing to Propylthiouracil,hypoglycemia reduced.
Pierpaolo Mastroiacovo - One of the best experts on this subject based on the ideXlab platform.
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treatment of hyperthyroidism in pregnancy and birth defects
The Journal of Clinical Endocrinology and Metabolism, 2010Co-Authors: Maurizio Clementi, Elena Di Gianantonio, Matteo Cassina, Emanuele Leoncini, Lorenzo D Botto, Pierpaolo MastroiacovoAbstract:CONTEXT: Clinical hyperthyroidism is not uncommon in pregnancy, with a reported prevalence of 0.1 to 0.4%. The available antithyroid drugs are Propylthiouracil and methimazole/carbimazole. OBJECTIVES: In this report we examined the association of both drugs with congenital malformations using data from the International Clearinghouse for Birth Defects Surveillance and Research. DESIGN: The study used a case-affected control analysis and included 18,131 cases with malformations and reported first-trimester exposure to medication. A total of 127 subjects were born to mothers with known first-trimester antithyroid drug exposure. RESULTS: Among the 52 groups of malformations that were analyzed, situs inversus ± dextrocardia, isolated unilateral kidney a/dysgenesis, and cardiac outflow tract defects were associated with prenatal exposure to Propylthiouracil based on three, two, and five cases, respectively. Prenatal exposure to methimazole/carbimazole was significantly associated with choanal atresia, omphalocele, and total situs inversus ± dextrocardia (P < 0.01). CONCLUSIONS: Further studies are required to exhaustively evaluate the associations between Propylthiouracil and birth defects because of the low number, the lack of biological plausibility, and the possibility of underdiagnosis. Association between methimazole/carbimazole exposure and omphalocele and choanal atresia is consistent with previous reports and definitely suggests that these malformations could be part of a specific, even if rare, embryopathy.
Bruno Le Bizec - One of the best experts on this subject based on the ideXlab platform.
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determination of thyreostats in urine and thyroid gland by ultra high performance liquid chromatography tandem mass spectrometry
Journal of Chromatography A, 2009Co-Authors: Madis Lohmus, Kalle Kallaste, Bruno Le BizecAbstract:Abstract Thyreostatic compounds could be illegally administered to animals in order to obtain a weight gain due to a higher retention of water in the edible tissue and the gastro-intestinal tract. In the European Union their use for animal production is banned since 1981. Recently a highly sensitive method exploiting the determination of thyreostats with 3-iodobenzylbromide prior to purification to determine thyreostats in urine and other matrices was reported. For the first time, the UPLC instrumentation was used to separate the 3-iodobenzyl derivatives of various thyreostats. The deuterated internal standards tapazole-d3 and Propylthiouracil-d5 were for the first time used for the quantification of tapazole, thiouracil, methylthiouracil, Propylthiouracil, phenylthiouracil and mercaptobenzimidazole. The confirmative quantitative liquid chromatographic tandem mass spectrometric (LC–MS/MS) method was validated according to Commission Decision 2002/657/EC. The decision limit (CCα) and the detection capability (CCβ) were found to be for all compounds below the recommended value of 10 μg kg−1.
