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[PMID]: 29381025 [Au] Autor: Bogatyrev AN; Dydykin AS; Asianova MA; Fedulova LV; Ustinova AV [Ti] Título: [Assessment of the using effectiveness of iodine containing additives in development of meat products for child nutrition]. [So] Source: Vopr Pitan;85(4):68-75, 2016. [Is] ISSN: 0042-8833 [Cp] País de publicação: Russia (Federation) [La] Idioma: rus [Ab] Resumo: The effectiveness of iodine containing additives on the basis of whey protein and milk protein casein compared to iodized salt in the composition of meat minced semi-finished products for child nutrition was examined in the experiment on laboratory animals. Four variants of the semi-finished products were investigated: 1 - control; 2 - enriched with iodine containing milk protein casein; 3 - enriched with iodine containing whey proteins; 4 - enriched with iodized salt. The semi-finished products were enriched at the level of 15% of the daily norm of iodine requirement for children at the age of 7-12 years. Iodine content in 100 g of product was 20 µkg. Rats (initial body weight 140±20 g, n=80) were divided into five groups (control, intact and three experimental groups). Groups 1 and 5 included the animals fed with a standard vivarium diet throughout the experiment. The rats from groups 2-4 were fed with the iodine enriched diet: group 2 received diet containing semi-finished products No. 2; group 3 sample No. 3 and group 4 - sample No. 4. The first stage of the experiment was aimed at accumulation of iodine in tissues and organs of animals consumed the tested iodine containing additives in the composition of semi-finished products. The second stage of the experiment consisted in simulation of the mercazolilum-induced (50 mg/kg b.w.) hypothyroidism (iodine deficiency) and detection of preventive effects of iodine containing meat semi-finished products in a model of experimental hypothyroidism in rats. The data obtained upon the end of the experiment suggest that the highest effect for correction of iodine deficiency was achieved when using the culinary products enriched with iodine containing whey proteins (sample No. 3): the level of thyroxine (T4) was restored by 98.7% in the animals from group 3 compared to the indices of the intact group, Т3 by 100%, TSH - by 89.3%. This effect was confirmed by the hematological and biochemical blood indexes, as well as the dynamics of their weight change: the level of white blood cells was significantly lower by 28%, granulocytes by 44%, monocytes by 42% compared to control rats; the weight gain of the animals of the 3 group was 20.3%, closer to that of intact animals - 26.4%, while in the control group it was 2.6 %. [Mh] Termos MeSH primário: Culinária Aditivos Alimentares/farmacologia Hipotireoidismo/sangue Hipotireoidismo/dietoterapia Iodo/farmacologia Produtos da Carne [Mh] Termos MeSH secundário: Animais Hipotireoidismo/induzido quimicamente Masculino Metimazol/efeitos adversos Metimazol/farmacologia Ratos Ratos Wistar [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Food Additives); 554Z48XN5E (Methimazole); 9679TC07X4 (Iodine) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180216 [Lr] Data última revisão: 180216 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180131 [St] Status: MEDLINE

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[PMID]: 29390469 [Au] Autor: Zeng XX; Tang YL; Hu KX; Wang J; Zhu LY; Liu JY; Xu J [Ad] Endereço: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. [Ti] Título: Insulin autoimmune syndrome in a pregnant female: A rare case report. [So] Source: Medicine (Baltimore);96(51):e9213, 2017 Dec. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: RATIONALE: Insulin autoimmune syndrome (IAS) is an uncommon disorder characterized by hyperinsulinemic hypoglycemia related to insulin-binding autoantibodies. To the best of our knowledge, we report the first case of a pregnant female with IAS. PATIENT CONCERNS: The 26-year-old patient with Graves disease and 10 weeks pregnant developed IAS after approximately 6 months treatment with methimazole. The patient exhibited recurrent spontaneous hypoglycemia. DIAGNOSES: On evaluation, laboratory findings detected both high fasting insulin (>1000 mIU/L) and insulin autoantibodies. An oral glucose tolerance test showed elevated insulin concentrations with disproportionately elevated C-peptide levels. The imaging study showed nomasslesionsinthepancreas,and the patient was clinically diagnosed with IAS. INTERVENTIONS: The patient had an abortion, discontinued methimazole and switched to oral prednisone (30 mg once daily) and propylth- iouracil (100 mg 3 times daily) for 3 months. OUTCOMES: At the 3-month follow-up visit, hypoglycemic episodes had disappeared and insulin antibody levels were no longer detectable. LESSONS: We have described this case and reviewed the relevant literature concerning diagnosis and treatment of IAS. Importantly, this case indicates that clinicians should view pregnancy as another factor of hypoglycemia in IAS. [Mh] Termos MeSH primário: Doenças Autoimunes/diagnóstico Hipoglicemia/induzido quimicamente Insulina/sangue Metimazol/efeitos adversos Complicações na Gravidez/diagnóstico [Mh] Termos MeSH secundário: Aborto Espontâneo Adulto Feminino Seguimentos Idade Gestacional Doença de Graves/diagnóstico Doença de Graves/tratamento farmacológico Seres Humanos Hipoglicemia/imunologia Hipoglicemia/fisiopatologia Insulina/imunologia Anticorpos Anti-Insulina/sangue Metimazol/uso terapêutico Prednisona/uso terapêutico Gravidez Doenças Raras Medição de Risco Síndrome [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Insulin); 0 (Insulin Antibodies); 554Z48XN5E (Methimazole); VB0R961HZT (Prednisone) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180214 [Lr] Data última revisão: 180214 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 180203 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000009213

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[PMID]: 29245333 [Au] Autor: Ji H; Yue F; Song J; Zhou X [Ad] Endereço: aDepartment of Pharmacy, Affiliated Yancheng Hospital of Southeast University Medical CollegebDepartment of Pharmacy, Sir Runrun Hospital, Nanjing Medical UniversitycDepartment of Hepatobiliary Surgery, Affiliated Yancheng Hospital of Southeast University Medical College, Jiangsu, China. [Ti] Título: A rare case of methimazole-induced cholestatic jaundice in an elderly man of Asian ethnicity with hyperthyroidism: A case report. [So] Source: Medicine (Baltimore);96(49):e9093, 2017 Dec. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: Methimazole is an antithyroid drug that is widely used for the treatment of hyperthyroidism. As an inhibitor of the enzyme thyroperoxidase, methimazole is generally well-tolerated. However, there have been increasing reports of methimazole-induced liver damage, although this effect of methimazole has been limited by the absence of objective diagnosis of the liver condition or the inappropriate use of the Naranjo scale. We present the case of an elderly man with hyperthyroidism, gastritis, and epilepsy who developed liver damage after administration of multiple drugs. KEY POINTS FROM THE CASE: Considering the low sensitivity of the Naranjo scale in detecting rare reactions associated with liver damage, we used the Roussel-Uclaf Causality Assessment Method scale, with a finding of cholestatic jaundice hepatitis induced by methimazole. The patient's liver enzyme levels improved after discontinuation of methimazole. MAIN LESSONS LEARNED: Our case underlines the possible hepatoxicity associated with the use of methimazole. A review of the literature confirmed a selective hepatoxicity risk in individuals of Asian ethnicity, which has not been identified in Caucasian or Black populations. Physicians should be aware of the risk of hepatoxicity when prescribing oral methimazole to patients of Asian ethnicity. [Mh] Termos MeSH primário: Antitireóideos/efeitos adversos Doença Hepática Induzida por Substâncias e Drogas/etiologia Icterícia Obstrutiva/induzido quimicamente Metimazol/efeitos adversos [Mh] Termos MeSH secundário: Idoso Antitireóideos/uso terapêutico Grupo com Ancestrais do Continente Asiático Seres Humanos Hipertireoidismo/tratamento farmacológico Testes de Função Hepática Masculino Metimazol/uso terapêutico [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antithyroid Agents); 554Z48XN5E (Methimazole) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180105 [Lr] Data última revisão: 180105 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 171217 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000009093

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[PMID]: 28458607 [Au] Autor: Kim HJ; Bang JI; Kim JY; Moon JH; So Y; Lee WW [Ad] Endereço: Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea. [Ti] Título: Novel Application of Quantitative Single-Photon Emission Computed Tomography/Computed Tomography to Predict Early Response to Methimazole in Graves' Disease. [So] Source: Korean J Radiol;18(3):543-550, 2017 May-Jun. [Is] ISSN: 2005-8330 [Cp] País de publicação: Korea (South) [La] Idioma: eng [Ab] Resumo: OBJECTIVE: Since Graves' disease (GD) is resistant to antithyroid drugs (ATDs), an accurate quantitative thyroid function measurement is required for the prediction of early responses to ATD. Quantitative parameters derived from the novel technology, single-photon emission computed tomography/computed tomography (SPECT/CT), were investigated for the prediction of achievement of euthyroidism after methimazole (MMI) treatment in GD. MATERIALS AND METHODS: A total of 36 GD patients (10 males, 26 females; mean age, 45.3 ± 13.8 years) were enrolled for this study, from April 2015 to January 2016. They underwent quantitative thyroid SPECT/CT 20 minutes post-injection of Tc-pertechnetate (5 mCi). Association between the time to biochemical euthyroidism after MMI treatment and %uptake, standardized uptake value (SUV), functional thyroid mass (SUVmean × thyroid volume) from the SPECT/CT, and clinical/biochemical variables, were investigated. RESULTS: GD patients had a significantly greater %uptake (6.9 ± 6.4%) than historical control euthyroid patients (n = 20, 0.8 ± 0.5%, < 0.001) from the same quantitative SPECT/CT protocol. Euthyroidism was achieved in 14 patients at 156 ± 62 days post-MMI treatment, but 22 patients had still not achieved euthyroidism by the last follow-up time-point (208 ± 80 days). In the univariate Cox regression analysis, the initial MMI dose ( = 0.014), %uptake ( = 0.015), and functional thyroid mass ( = 0.016) were significant predictors of euthyroidism in response to MMI treatment. However, only %uptake remained significant in a multivariate Cox regression analysis ( = 0.034). A %uptake cutoff of 5.0% dichotomized the faster responding versus the slower responding GD patients ( = 0.006). CONCLUSION: A novel parameter of thyroid %uptake from quantitative SPECT/CT is a predictive indicator of an early response to MMI in GD patients. [Mh] Termos MeSH primário: Doença de Graves/diagnóstico por imagem Tomografia Computadorizada de Emissão de Fóton Único [Mh] Termos MeSH secundário: Adulto Antitireóideos/uso terapêutico Feminino Doença de Graves/tratamento farmacológico Doença de Graves/patologia Seres Humanos Masculino Metimazol/uso terapêutico Meia-Idade Modelos de Riscos Proporcionais Pertecnetato Tc 99m de Sódio/química Tireotropina/análise [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Antithyroid Agents); 554Z48XN5E (Methimazole); 9002-71-5 (Thyrotropin); A0730CX801 (Sodium Pertechnetate Tc 99m) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 180102 [Lr] Data última revisão: 180102 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170502 [St] Status: MEDLINE [do] DOI: 10.3348/kjr.2017.18.3.543

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[PMID]: 28953662 [Au] Autor: Abramavicius S; Velickiene D; Kadusevicius E [Ad] Endereço: aInstitute of Physiology and Pharmacology, Lithuanian University of Health Sciences bInstitute of Endocrinology, Lithuanian University of Health Sciences cInstitute of Physiology and Pharmacology, Lithuanian University of Health Sciences, Kaunas, Lithuania. [Ti] Título: Methimazole-induced liver injury overshadowed by methylprednisolone pulse therapy: Case report. [So] Source: Medicine (Baltimore);96(39):e8159, 2017 Sep. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: RATIONALE: Treatment choices are limited, when deciding how to manage thyrotoxicosis and moderate to severe Graves ophthalmopathy (GO) with suspected optic nerve damage in patients with elevated liver transaminase levels. The situation become even more complicated, if methimazole induced hepatotoxicity is suspected and intravenous methylprednisolone is co-administrated. PATIENT CONCERNS: A 74-year-old woman presented with spontaneous retro-bulbar pain, eyelid swelling and inconstant diplopia. DIAGNOSES: Thyrotoxicosis and severe GO with suspected optic nerve damage and drug induced liver injury (DILI). INTERVENTIONS: Intravenous methylprednisolone pulse therapy was administered to treat GO and methimazole was continued for thyrotoxicosis. Dose of methimazole was reduced after exclusion of concurrent infection and active liver disease. OUTCOMES: The GO symptoms (eyelid swelling, sight loss, proptosis, retro-bulbar pain, diplopia) markedly decreased after the treatment course. Liver transaminases spontaneously returned to normal ranges and remained normal during the next 12 months until the Graves' disease until the treatment was completed. LESSONS: 1. The interaction of methimazole and methylprednisolone may result in DILI. 2. In a patient without concomitant liver diseases MP can be continued if the methimazole dose is reduced if no other treatment options are available. [Mh] Termos MeSH primário: Doença Hepática Induzida por Substâncias e Drogas Oftalmopatia de Graves Metimazol Metilprednisolona Doenças do Nervo Óptico Tireotoxicose [Mh] Termos MeSH secundário: Administração Intravenosa Idoso Antitireóideos/administração & dosagem Antitireóideos/efeitos adversos Doença Hepática Induzida por Substâncias e Drogas/diagnóstico Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia Doença Hepática Induzida por Substâncias e Drogas/terapia Relação Dose-Resposta a Droga Feminino Glucocorticoides/administração & dosagem Glucocorticoides/efeitos adversos Oftalmopatia de Graves/diagnóstico Oftalmopatia de Graves/tratamento farmacológico Oftalmopatia de Graves/fisiopatologia Seres Humanos Testes de Função Hepática Conduta do Tratamento Medicamentoso Metimazol/administração & dosagem Metimazol/efeitos adversos Metilprednisolona/administração & dosagem Metilprednisolona/efeitos adversos Doenças do Nervo Óptico/complicações Doenças do Nervo Óptico/diagnóstico Doenças do Nervo Óptico/fisiopatologia Pulsoterapia/métodos Avaliação de Sintomas/métodos Tireotoxicose/complicações Tireotoxicose/diagnóstico Tireotoxicose/fisiopatologia Resultado do Tratamento [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antithyroid Agents); 0 (Glucocorticoids); 554Z48XN5E (Methimazole); X4W7ZR7023 (Methylprednisolone) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171016 [Lr] Data última revisão: 171016 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170928 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000008159

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[PMID]: 28671971 [Au] Autor: Song R; Lin H; Chen Y; Zhang X; Feng W [Ad] Endereço: Department of Pharmacy, Peking University People's Hospital, Beijing, China. [Ti] Título: Effects of methimazole and propylthiouracil exposure during pregnancy on the risk of neonatal congenital malformations: A meta-analysis. [So] Source: PLoS One;12(7):e0180108, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVE: The aim of this study was to determine the effect of exposure to different antithyroid drugs during pregnancy on the incidence of neonatal congenital malformations. METHODS: A meta-analysis was performed to compare the incidence of neonatal congenital malformations after exposure to different antithyroid drugs during pregnancy. Twelve studies that met the inclusion criteria were included in this meta-analysis. PubMed, Embase, and CENTRAL databases were searched from inception until January 2017. Study designs included case-control studies, prospective cohort studies, and retrospective cohort studies. RESULTS: Twelve studies involving 8028 participants with exposure to different antithyroid drugs during pregnancy were included in this study; however, only 10 studies involving 5059 participants involved exposure to different antithyroid drugs exactly during pregnancy. Our results indicated that exposure to methimazole (MMI)/carbimazole (CMZ) only during pregnancy significantly increased the risk of neonatal congenital malformations compared to no antithyroid drug exposure (OR 1.88; 95%CI 1.33 to 2.65; P = 0.0004). No differences were observed between propylthiouracil (PTU) exposure and no antithyroid drug exposure only during pregnancy (OR 0.81; 95%CI 0.58 to 1.15; P = 0.24). Exposure to MMI/CMZ only during pregnancy significantly increased the risk of neonatal congenital malformations compared to that associated with exposure to PTU (OR 1.90; 95%CI 1.30 to 2.78; P = 0.001). CONCLUSION: For pregnant women with hyperthyroidism, exposure to MMI/CMZ significantly increased the incidence of neonatal congenital malformations compared to exposure to PTU and no antithyroid drug exposure; however, no differences were observed between PTU exposure and no antithyroid drug exposure. [Mh] Termos MeSH primário: Anormalidades Induzidas por Medicamentos Antitireóideos/efeitos adversos Metimazol/efeitos adversos Propiltiouracila/efeitos adversos [Mh] Termos MeSH secundário: Antitireóideos/uso terapêutico Feminino Seres Humanos Recém-Nascido Metimazol/uso terapêutico Gravidez Propiltiouracila/uso terapêutico [Pt] Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS [Nm] Nome de substância: 0 (Antithyroid Agents); 554Z48XN5E (Methimazole); 721M9407IY (Propylthiouracil) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171006 [Lr] Data última revisão: 171006 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170704 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0180108

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[PMID]: 28653416 [Au] Autor: Sirohi HV; Singh PK; Iqbal N; Sharma P; Singh AK; Kaur P; Sharma S; Singh TP [Ad] Endereço: Department of Biophysics, All India Institute of Medical Sciences, New Delhi. [Ti] Título: Design of anti-thyroid drugs: Binding studies and structure determination of the complex of lactoperoxidase with 2-mercaptoimidazole at 2.30 Å resolution. [So] Source: Proteins;85(10):1882-1890, 2017 Oct. [Is] ISSN: 1097-0134 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Lactoperoxidase (LPO) belongs to mammalian heme peroxidase superfamily, which also includes myeloperoxidase (MPO), eosinophil peroxidase (EPO), and thyroid peroxidase (TPO). LPO catalyzes the oxidation of a number of substrates including thiocyanate while TPO catalyzes the biosynthesis of thyroid hormones. LPO is also been shown to catalyze the biosynthesis of thyroid hormones indicating similar functional and structural properties. The binding studies showed that 2-mercaptoimidazole (MZY) bound to LPO with a dissociation constant of 0.63 µM. The inhibition studies showed that the value of IC was 17 µM. The crystal structure of the complex of LPO with MZY showed that MZY bound to LPO in the substrate-binding site on the distal heme side. MZY was oriented in the substrate-binding site in such a way that the sulfur atom is at a distance of 2.58 Å from the heme iron. Previously, a similar compound, 3-amino-1,2,4-triazole (amitrole) was also shown to bind to LPO in the substrate-binding site on the distal heme side. The amino nitrogen atom of amitrole occupied the same position as that of sulfur atom in the present structure indicating a similar mode of binding. Recently, the structure of the complex of LPO with a potent antithyroid drug, 1-methylimidazole-2-thiol (methimazole, MMZ) was also determined. It showed that MMZ bound to LPO in the substrate-binding site on the distal heme side with 2 orientations. The position of methyl group was same in the 2 orientations while the positions of sulfur atom differed indicating a higher preference for a methyl group. [Mh] Termos MeSH primário: Etilenotioureia/análogos & derivados Lactoperoxidase/química Hormônios Tireóideos/química [Mh] Termos MeSH secundário: Sítios de Ligação Cristalografia por Raios X Etilenotioureia/química Etilenotioureia/metabolismo Heme/química Heme/metabolismo Seres Humanos Lactoperoxidase/metabolismo Metimazol/química Metimazol/uso terapêutico Conformação Proteica Especificidade por Substrato Enxofre Glândula Tireoide/química Glândula Tireoide/enzimologia Hormônios Tireóideos/biossíntese [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Thyroid Hormones); 24FOJ4N18S (Ethylenethiourea); 42VZT0U6YR (Heme); 554Z48XN5E (Methimazole); 70FD1KFU70 (Sulfur); 872-35-5 (2-mercaptoimidazole); EC 1.11.1.- (Lactoperoxidase) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171016 [Lr] Data última revisão: 171016 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170628 [St] Status: MEDLINE [do] DOI: 10.1002/prot.25342

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[PMID]: 28428265 [Au] Autor: Ma H; Yang F; Butler MR; Belcher J; Redmond TM; Placzek AT; Scanlan TS; Ding XQ [Ad] Endereço: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. [Ti] Título: Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. [So] Source: FASEB J;31(8):3425-3438, 2017 Aug. [Is] ISSN: 1530-6860 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have implicated TH signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we demonstrated that antithyroid drug treatment and targeting iodothyronine deiodinases (DIOs) to suppress cellular tri-iodothyronine (T3) production or increase T3 degradation preserves cones. In this work, we investigated the effectiveness of inhibition of the TH receptor (TR). Two genes, and , encode TRs; 2 has been associated with cone viability. Using TR antagonists and deletion, we examined the effects of TR inhibition. Systemic and ocular treatment with the TR antagonists NH-3 and 1-850 increased cone density by 30-40% in the mouse model of Leber congenital amaurosis and reduced the number of TUNEL cells. Cone survival was significantly improved in and (a model of achromatopsia with defect) mice with deletion. Ventral cone density in and / mice was increased by 1- to 4-fold, compared with age-matched controls. Moreover, the expression levels of TR were significantly higher in the cone-degeneration retinas, suggesting locally elevated TR signaling. This work shows that the effects of antithyroid treatment or targeting DIOs were likely mediated by TRs and that suppressing TR protects cones. Our findings support the view that inhibition of TR locally in the retina is a therapeutic strategy for retinal degeneration management.-Ma, H., Yang, F., Butler, M. R., Belcher, J., Redmond, T. M., Placzek, A. T., Scanlan, T. S., Ding, X.-Q. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. [Mh] Termos MeSH primário: Antitireóideos/farmacologia Metimazol/farmacologia Receptores dos Hormônios Tireóideos/antagonistas & inibidores Retina/metabolismo Degeneração Retiniana/tratamento farmacológico [Mh] Termos MeSH secundário: Animais Antitireóideos/uso terapêutico Fatores de Transcrição de Zíper de Leucina Básica/genética Fatores de Transcrição de Zíper de Leucina Básica/metabolismo Morte Celular Modelos Animais de Doenças Proteínas do Olho/genética Proteínas do Olho/metabolismo Deleção de Genes Regulação da Expressão Gênica/efeitos dos fármacos Regulação da Expressão Gênica/fisiologia Metimazol/uso terapêutico Camundongos Camundongos Endogâmicos C57BL Camundongos Knockout Fenoxiacetatos/farmacologia Receptores dos Hormônios Tireóideos/genética Receptores dos Hormônios Tireóideos/metabolismo Células Fotorreceptoras Retinianas Cones/metabolismo Degeneração Retiniana/metabolismo Degeneração Retiniana/patologia Retinoblastoma Tri-Iodotironina cis-trans-Isomerases/genética cis-trans-Isomerases/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 ((4-(4-hydroxy-3-isopropyl-5-(4-nitrophenylethynyl)benzyl)-3,5-dimethylphenoxy)acetic acid); 0 (Antithyroid Agents); 0 (Basic-Leucine Zipper Transcription Factors); 0 (Eye Proteins); 0 (Nrl protein, mouse); 0 (Phenoxyacetates); 0 (Receptors, Thyroid Hormone); 06LU7C9H1V (Triiodothyronine); 554Z48XN5E (Methimazole); EC 3.1.1.64 (retinoid isomerohydrolase); EC 5.2.- (cis-trans-Isomerases) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171111 [Lr] Data última revisão: 171111 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170422 [St] Status: MEDLINE [do] DOI: 10.1096/fj.201601166RR

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[PMID]: 28341216 [Au] Autor: Wei Q; Hu B; Xue Y; Mburu DK; Tao X; Su J [Ad] Endereço: Department of Pesticide Sciences, College of Plant Protection, Nanjing Agricultural University, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing, China. [Ti] Título: Effects of methimazole on Drosophila glucolipid metabolism in vitro and in vivo. [So] Source: Comp Biochem Physiol C Toxicol Pharmacol;196:54-60, 2017 Jun. [Is] ISSN: 1532-0456 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Methimazole (MMI) is an antithyroid agent widely used in the treatment of hyperthyroidism, and metabolized by cytochrome P450 enzymes and flavin-containing monooxygenases in mammals. However, drug overdose and the inadequate detoxification of the metabolite(s) are responsible for hepatocellular damage and organ dysfunction. Depending on the desired properties, Drosophila melanogaster has recently emerged as an ideal model organism for the study of human diseases. Here we investigated the changes in metabolic profiles and mRNA expressions related to glucolipid metabolism in response to treatment with MMI in Drosophila. Remarkable loss of lifespan occurred in fruit flies fed on the diets containing 10 or 30mM MMI compared to unsupplemented controls. To examine whether MMI affects glucolipid metabolism in vitro and in vivo, fruit flies were fed diets containing 30mM MMI for two weeks and Drosophila S2 cells were incubated with 300µM MMI for 48h. Measurements of metabolites showed that triglyceride content dramatically decreased (30.56% in vivo and 18.13% in vitro), and glycogen content significantly increased (10.7% in vivo and 126.8% in vitro). Quantitative analyses indicated that mRNA expression levels of Dmfmo1, s6k, dilp2, acc and dilp5 genes involved in metabolic homeostasis were remarkably down-regulated in vivo and in vitro. Meanwhile, the addition of MMI could significantly reduce the lipid droplet content in S2 cells by approximately 25% compared to control subjects. These data may provide a biological basis for the study of MMI on disease symptoms and complications, and discovery of therapeutic treatments. [Mh] Termos MeSH primário: Antitireóideos/toxicidade Metabolismo dos Carboidratos/efeitos dos fármacos Drosophila melanogaster/efeitos dos fármacos Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos Proteínas de Insetos/metabolismo Metabolismo dos Lipídeos/efeitos dos fármacos Metimazol/toxicidade [Mh] Termos MeSH secundário: Animais Linhagem Celular Proliferação Celular/efeitos dos fármacos Sobrevivência Celular/efeitos dos fármacos Drosophila melanogaster/citologia Drosophila melanogaster/crescimento & desenvolvimento Drosophila melanogaster/fisiologia Perfilação da Expressão Gênica Glicogênio/agonistas Glicogênio/biossíntese Proteínas de Insetos/antagonistas & inibidores Proteínas de Insetos/genética Dose Letal Mediana Gotículas Lipídicas/efeitos dos fármacos Gotículas Lipídicas/metabolismo Longevidade/efeitos dos fármacos Masculino RNA Mensageiro/metabolismo Análise de Sobrevida Testes de Toxicidade Aguda Testes de Toxicidade Crônica Triglicerídeos/antagonistas & inibidores Triglicerídeos/biossíntese [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antithyroid Agents); 0 (Insect Proteins); 0 (RNA, Messenger); 0 (Triglycerides); 554Z48XN5E (Methimazole); 9005-79-2 (Glycogen) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170809 [Lr] Data última revisão: 170809 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170326 [St] Status: MEDLINE

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MEDLINE

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[PMID]: 28324105 [Au] Autor: Tabachnik T; Kisliouk T; Marco A; Meiri N; Weller A [Ad] Endereço: Faculty of Life Sciences, Bar Ilan University, Ramat-Gan, Israel. [Ti] Título: Thyroid Hormone-Dependent Epigenetic Regulation of Melanocortin 4 Receptor Levels in Female Offspring of Obese Rats. [So] Source: Endocrinology;158(4):842-851, 2017 04 01. [Is] ISSN: 1945-7170 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Maternal obesity is a risk factor for offspring obesity. The melanocortin 4 receptor (Mc4r) is one of the mediators of food intake and energy balance. The present study examined the epigenetic mechanisms underlying altered Mc4r levels in the hypothalamic paraventricular nucleus in the offspring of high-fat diet (HFD)-induced obese dams and sought to elucidate the role of thyroid hormones in epigenetic regulation and tagging of their nucleosome at the Mc4r promoter. Female Wistar rats were fed an HFD or standard chow from weaning through gestation and lactation. Epigenetic alterations were analyzed in the offspring on postnatal day 21 at the Mc4r promoter using chromatin immunoprecipitation and bisulfite sequencing. To study the role of triiodothyronine (T3) in Mc4r downregulation, dams received methimazole (MMI), an inhibitor of thyroid hormone production. Offspring of HFD-fed dams had a greater body weight, elevated plasma T3 concentrations, and lower Mc4r messenger RNA levels than controls. At the Mc4r promoter, offspring of HFD-fed mothers demonstrated increased histone 3 lysine 27 acetylation (H3K27ac) with a greater association to thyroid hormone receptor-ß (TRß), an inhibitor of Mc4r transcription. Moreover, TRß coimmunoprecipitated with H3K27ac, supporting their presence in the same complex. Maternal MMI administration prevented the HFD reduction in Mc4r levels, the increase in TRß, and the increase in the TRß-H3K27ac association, providing further support for the role of T3 in downregulating Mc4r levels. These findings demonstrate that a perinatal HFD environment affects Mc4r regulation through a T3 metabolic pathway involving histone acetylation of its promoter. [Mh] Termos MeSH primário: Epigênese Genética Receptor Tipo 4 de Melanocortina/metabolismo Tri-Iodotironina/metabolismo [Mh] Termos MeSH secundário: Animais Peso Corporal/efeitos dos fármacos Peso Corporal/fisiologia Ingestão de Alimentos/efeitos dos fármacos Ingestão de Alimentos/fisiologia Feminino Fenômenos Fisiológicos da Nutrição Materna Metimazol/farmacologia Obesidade/metabolismo Gravidez Regiões Promotoras Genéticas Ratos Ratos Wistar Receptor Tipo 4 de Melanocortina/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Receptor, Melanocortin, Type 4); 06LU7C9H1V (Triiodothyronine); 554Z48XN5E (Methimazole) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170707 [Lr] Data última revisão: 170707 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170322 [St] Status: MEDLINE [do] DOI: 10.1210/en.2016-1854

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