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1.
J Proteomics ; 274: 104811, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36592655

RESUMO

The central goal of this study was to investigate the alterations in transcriptome of testis in F1 generation adult rats exposed to carbimazole prenatally. At post-natal day 100, the testis of rats delivered to carbimazole exposed (time-mated pregnant rats orally administered with carbimazole from gestation day 9 to 21) and control (untreated pregnant rats) groups were subjected to transcriptomic analysis using NGS platform. A total of 187 differentially expressed (up regulated: 49 genes; down regulated: 138) genes were identified in carbimazole exposed rats over controls and the major processes associated with these altered testicular transcripts were examined. Functional clustering analysis suggest that the involvement of identified DEGs were linked to intrinsic and extrinsic apoptotic pathways, mitochondrial solute carriers slc25a members, nuclear receptors/zinc family members, steroidogenic pathway and cholesterol synthesis, and growth factors and protein kinases and thus represent potential mediators of the developmental toxic effects of carbimazole in F1 generation rats. Based on the findings, it can be concluded that prenatal exposure to carbimazole prominently affects expression of multiple transcripts implicating key regulatory events associated with testicular functions, spermatogenesis and steroidogenesis in rats at their adulthood. These results support our earlier findings and hypothesis. This background information obtained at the testicular transcriptome during gestational hypothyroidism might be helpful for future studies and experiments to gain additional in-depth analysis and to develop strategies to protect F1 generation male reproductive health. SIGNIFICANCE: The rationale for the paper described thyroid gland changes in the off springs. Antithyroid drugs are widely used to control thyroid disorders and used to control thyroid hormone levels during surgeries. Carbimazole is one of the antithyroid drugs and is a parent molecule of methimazole. Both the drugs can able to cross placenta. During fetal period, the development of thyroid gland is not completely formed and hence, the fetus entirely depends on the maternal thyroid hormones. Therefore, it is conceivable that the disturbances at the level of maternal thyroid hormones could interfere with the development of vital organs such as testis and glands including thyroid gland (Kala et al., 2012). To address this notion, the present study was designed and executed.


Assuntos
Antitireóideos , Carbimazol , Gravidez , Feminino , Ratos , Masculino , Animais , Carbimazol/metabolismo , Carbimazol/farmacologia , Antitireóideos/toxicidade , Transcriptoma , Testículo/metabolismo , Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/farmacologia
2.
BMJ Case Rep ; 15(8)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35985738

RESUMO

Hypercalcaemia in patients with hyperthyroidism is usually asymptomatic. It occurs due to increased bone turnover and demineralisation. There are only a few case reports where symptomatic hypercalcaemia was the presenting complaint of hyperthyroidism. An Asian man in his 40s presented to us with intractable vomiting for the last 6 months which was not controlled despite multiple antiemetic medications. On routine biochemistry performed at our institute, he was found to have hypercalcaemia and concomitant hyperthyroidism. Classical symptoms suggestive of hyperthyroidism were not present in our patient thus delaying the diagnosis. His symptoms resolved after the correction of hypercalcaemia. Hypercalcaemia did not recur after achieving an euthyroid status on treatment with carbimazole. Other common and more sinister causes for hypercalcaemia like malignancy were ruled out. This case highlights that symptomatic hypercalcaemia could be the initial presentation of hyperthyroidism and amelioration of hyperthyroidism corrects the hypercalcaemia.


Assuntos
Doença de Graves , Hipercalcemia , Hipertireoidismo , Antitireóideos/uso terapêutico , Carbimazol/uso terapêutico , Doença de Graves/complicações , Doença de Graves/diagnóstico , Doença de Graves/tratamento farmacológico , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/tratamento farmacológico , Hipercalcemia/etiologia , Hipertireoidismo/complicações , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Masculino
3.
Life Sci ; 307: 120904, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36029850

RESUMO

Most of the published experiments about carbimazole (CMZ)-induced testicular injury are constructed in normal healthy animals, which lakes the translational identification. Despite metformin (MET) having advantageous effects on injured testicles, its impact on thyroid function is arguable. In the current levothyroxine (LT4)/CMZ model, Wistar rats were primed by LT4 for sixty days. CMZ was then given individually or simultaneously with different doses of MET, 100, 200, and 400 mg, daily for thirty days. Serum was assessed for thyroid profile panel, sex hormones, and gonadotropin levels. Testicular tissues were examined for steroidogenesis, spermatogenesis, inflammation, and apoptosis. Histopathology of thyroid and testes were examined, besides thyroidal nuclear factor (NF)-kB expression. MET in a dose-response manner improved the LT4/CMZ-induced testicular toxicity by increasing the steroidogenic acute regulatory protein (StAR), and 17-ß-hydroxysteroid dehydrogenase (17ßHSD) activities, the proliferating cell nuclear antigen (PCNA), sperm count and motility, sex hormones, and gonadotropin levels. MET-400 mg markedly decreased the elevated NF-kB expressions, tumour necrosis factor (TNF)-α, caspase-3, and BAX, and increased BCL-2. LT4/CMZ could be used as translational animal modelling. MET displayed a dose-dependent ameliorative effect on the LT4/CMZ model without significant harmful effects on thyroid functions. MET-testicular protective roles in diabetics with thyroidal diseases should be explored.


Assuntos
Metformina , Testículo , Animais , Carbimazol/metabolismo , Carbimazol/farmacologia , Caspase 3/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Gonadotropinas/metabolismo , Masculino , Metformina/metabolismo , Metformina/farmacologia , NF-kappa B/metabolismo , Estresse Oxidativo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , Sêmen/metabolismo , Espermatogênese , Testosterona/metabolismo , Tiroxina/metabolismo , Fatores de Necrose Tumoral/metabolismo , Fatores de Necrose Tumoral/farmacologia , Proteína X Associada a bcl-2/metabolismo
4.
Mymensingh Med J ; 31(2): 553-555, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35383779

RESUMO

Conventional management of Graves' disease includes antithyroid drugs, radioactive iodine and thyroidectomy. Patients rarely may be resistant to antithyroid drugs and may require additional management, including corticosteroids. We treated an 18-year-old girl with Graves' thyrotoxicosis and resistance to Carbimazole. She was clinically and biochemically hyperthyroid despite getting 75mg Carbimazole and 120mg Propranolol daily. We added tablet Prednisolone (20mg for 15 days, then 10mg for the next 15 days) to Carbimazole (75mg/day). Four weeks later, she was free from thyrotoxic symptoms and her free T4 and total T3 levels normalized. The dose of tablet Prednisolone was lowered to 5mg/day for the next 15 days and Carbimazole was continued at 45mg/day. She received 10mCi Iodine-131 (131¹) at this stage and Carbimazole was discontinued. She remained clinically and biochemically euthyroid when she was followed up at 7th and 24th weeks after radioiodine ablation.


Assuntos
Doença de Graves , Neoplasias da Glândula Tireoide , Adolescente , Carbimazol/uso terapêutico , Feminino , Doença de Graves/tratamento farmacológico , Humanos , Radioisótopos do Iodo/uso terapêutico , Prednisolona/uso terapêutico
5.
Ultrastruct Pathol ; 46(1): 80-95, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35225157

RESUMO

BACKGROUND: Thyroid disorders are among the most common metabolic disorders worldwide. Thyroid dysfunction affects salivary glands function, causing hyposalivation. It also provokes physiological and histological changes in parotid, submandibular, and in particular the sublingual gland. THE AIM OF THIS WORK: The aim of this work was to clarify the histological and ultrastructural changes that occur in the parotid gland following carbimazole-induced hypothyroidism in adult male albino rats. The study also aims to investigate the possible protective role of L-thyroxin supplementation on the rat parotid glands after long and short duration of hypothyroidism. MATERIAL AND METHODS: Fifty-five adult male albino rats of Sprague Dawley strain; were divided into four groups and eleven subgroups, five rats each. G І received nothing. G П given normal saline orally daily. G Ш (medical Hypothyroidism, short duration - long duration - recovery group) given Carbimazole orally by gastric tube in a dose of 0.05 mg/kg daily for 3,6 successive weeks for group (a, b) and for 6 successive weeks then were left without any medication for another 3 weeks in recovery group c. G IV-b, c (L-Thyroxine supplemented group, short duration-long duration) given Carbimazole orally daily for 3,6 successive weeks then L-thyroxine was given orally in a dose of (10 µg/100 g/B.W) daily for another 3 successive weeks. Animals were sacrificed 24 hours after the last dose of Carbimazole in G III-a, b and 3 weeks after stoppage the drug in G III-c. Animals were sacrificed 24 hours after the last dose of L- Thyroxine in G IV-b, c. The parotid specimens were processed for histopathological examination by light and electron microscopy. The medically induced Hypothyroidism resulted in significant parotid gland damage which was more obvious with longer duration; as follow: a) most of the acini had irregular outlines and were widely separated with narrow lumen and cytoplasmic vacuoles. b) some acinar cells contained ill defined, irregular, pyknotic or hyperchromatic nuclei. c)Vascular changes: dilated and engorged with blood. d) the interlobular and striated ducts appeared disrupted and dilated. e) extravasated blood with cellular infiltration were seen in the interstitial space. IN CONCLUSION: Thyroid hormones (THs) had a significant effect in protection of parotid gland against damage induced by carbimazole, as it preserved the normal histological architecture of the parotid gland. This beneficial effect of THs was mostly related to its antioxidant properties. The expression of BCL-2 has certain regularity in apoptosis after drug administration. Regulation of glandular atrophy and apoptosis are closely related. The molecular mechanism of the apoptosis of the gland is not clear, and further study is needed in the future.


Assuntos
Hipotireoidismo , Tiroxina , Animais , Carbimazol/toxicidade , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/prevenção & controle , Masculino , Glândula Parótida/patologia , Ratos , Ratos Sprague-Dawley , Hormônios Tireóideos/efeitos adversos , Tiroxina/efeitos adversos
6.
J Neuroendocrinol ; 34(1): e13075, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34905237

RESUMO

Thyroid disease is known to affect brain metabolism and cognitive function, although the recovery of thyroid-induced brain functional changes after treatment remains unclear. We aimed to investigate the alteration in brain functional connectivity and its correlation with neuropsychological variables in hyperthyroid patients before and after anti-thyroid treatment using a resting-state functional magnetic resonance imaging (rsfMRI) technique. This is a follow-up rsfMRI study of previous work that showed impaired brain functional connectivity in hyperthyroid patients compared to healthy controls. We included rsfMRI and neuropsychological data from 21 hyperthyroid patients out of an original cohort of 28 patients, before and after anti-thyroid treatment for 30 weeks. Functional connectivity analysis and neuropsychological scores were compared using paired t tests in patients at baseline and at follow-up. Patients showed an improvement in some of the memory (p < .05) and executive, visuospatial and motor (p < .001) functions after treatment, and also showed increased functional connectivity in the regions of the right fronto-parietal network, left fronto-parietal network, and default mode network (DMN) (p < .05). At follow-up, the functional connectivity of the right fronto-parietal network showed a significantly positive correlation with the recognition of objects memory score. The overall findings suggest that anti-thyroid treatment with carbimazole improves the functional connectivity within some of the resting state networks in the hyperthyroid patients, whereas the remaining networks still show impairment.


Assuntos
Antitireóideos/uso terapêutico , Encéfalo/efeitos dos fármacos , Hipertireoidismo/tratamento farmacológico , Vias Neurais/efeitos dos fármacos , Adulto , Encéfalo/citologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Carbimazol/uso terapêutico , Cognição/efeitos dos fármacos , Estudos de Coortes , Função Executiva/efeitos dos fármacos , Feminino , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/fisiopatologia , Hipertireoidismo/psicologia , Índia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Testes Neuropsicológicos
8.
Clin Endocrinol (Oxf) ; 96(6): 857-868, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34845757

RESUMO

OBJECTIVES: The risk of congenital anomalies following in utero exposure to thionamide antithyroid drugs (ATDs) is unresolved. Observational studies are contradictory and existing meta-analyses predate and preclude more recent studies. We undertook an updated meta-analysis of congenital anomaly risk in women exposed to carbimazole or methimazole (CMZ/MMI), propylthiouracil (PTU), or untreated hyperthyroidism in pregnancy. METHODS: We searched Medline, Embase, and the Cochrane database for articles published up till August 2021. We pooled separate crude and adjusted risk estimates using random effects models and subgroup analyses to address heterogeneity. RESULTS: We identified 16 cohort studies comprising 5957, 15,785, and 15,666 exposures to CMZ/MMI, PTU, and untreated hyperthyroidism, respectively. Compared to nondisease controls, adjusted risk ratio (RR) and 95% confidence intervals (95% CIs) for congenital anomalies was increased for CMZ/MMI (RR, 1.28; 95% CI, 1.06-1.54) and PTU (RR, 1.16; 95% CI, 1.08-1.25). Crude risk for CMZ/MMI was increased relative to PTU (RR, 1.20; 95% CI, 1.01-1.43). Increased risk was also seen with exposure to both CMZ/MMI and PTU, that is, women who switched ATDs in pregnancy (RR, 1.51; 95% CI, 1.14-1.99). However, the timing of ATD switch was highly variable and included prepregnancy switches in some studies. The excess number of anomalies per 1000 live births was 17.2 for patients exposed to CMZ/MMI, 9.8, for PTU exposure, and 31.4 for exposure to both CMZ/MMI and PTU. Risk in the untreated group did not differ from control or ATD groups. The untreated group was however highly heterogeneous in terms of thyroid status. Subgroup analysis showed more positive associations in studies with >500 exposures and up to 1-year follow-up. CONCLUSIONS: ATD therapy carries a small risk of congenital anomalies which is higher for CMZ/MMI than for PTU and does not appear to be reduced by switching ATDs in pregnancy. Due to key limitations in the available data, further studies will be required to clarify the risks associated with untreated hyperthyroidism and with switching ATDs in pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos , Hipertireoidismo , Complicações na Gravidez , Anormalidades Induzidas por Medicamentos/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Antitireóideos/efeitos adversos , Carbimazol/efeitos adversos , Feminino , Humanos , Hipertireoidismo/tratamento farmacológico , Metimazol/efeitos adversos , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/tratamento farmacológico , Propiltiouracila/efeitos adversos
9.
BMJ Paediatr Open ; 6(1)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36645751

RESUMO

Thyrotoxicosis due to hyperthyroidism is a serious disorder in childhood often presenting to general paediatricians with a range of clinical manifestations. The commonest cause is Graves' disease, an autoimmune disorder resulting from thyrotropin receptor stimulation by autoantibodies. Early recognition and accurate interpretation of investigations are essential to achieve and maintain a euthyroid state. This will not only optimise growth, development and transition from childhood to young adult life but also avoid the potentially severe and life-threatening complications of acute thyrotoxicosis. In this review, we have focussed on the general paediatrician's perspective of the presentation and management of thyrotoxicosis and the need to network with specialist paediatric endocrine centres to optimise patient care. We have discussed nuances of therapy, side effects and long-term outcomes, while recognising that limited remission rates in this age group often necessitate more definitive management. While carbimazole is usually used as first-line medical therapy, we have provided useful information to guide paediatricians in the discussion of individualised safe and effective treatment plans for both short-term and long-term management.


Assuntos
Doença de Graves , Hipertireoidismo , Tireotoxicose , Adulto Jovem , Humanos , Criança , Adolescente , Antitireóideos/uso terapêutico , Tireotoxicose/diagnóstico , Tireotoxicose/tratamento farmacológico , Doença de Graves/complicações , Doença de Graves/diagnóstico , Doença de Graves/tratamento farmacológico , Hipertireoidismo/complicações , Hipertireoidismo/diagnóstico , Hipertireoidismo/terapia , Carbimazol/uso terapêutico
10.
BMJ Case Rep ; 14(11)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753719

RESUMO

Liver involvement in Graves' disease can be seen as a part of autoimmune process or rarely, due to the direct effects of thyrotoxicosis on liver. Hyperthyroidism can also have gastrointestinal manifestations like frequent bowel movements, diarrhoea, even malabsorption with steatorrhoea. We report a 36-year-old man with hyperthyroidism, presenting with cholestatic jaundice and persistent small bowel diarrhoea. He was diagnosed to have Graves' disease and after ruling out more common causes, the cause of cholestatic jaundice was supposed to be Graves' disease. Considering this possibility, the patient was started on treatment with carbimazole. As patient's thyroid function tests started improving, he showed significant clinical and biochemical improvement from liver point of view as well.


Assuntos
Doença de Graves , Icterícia Obstrutiva , Tireotoxicose , Adulto , Carbimazol/uso terapêutico , Diarreia/etiologia , Doença de Graves/complicações , Doença de Graves/diagnóstico , Doença de Graves/tratamento farmacológico , Humanos , Icterícia Obstrutiva/etiologia , Masculino
11.
Dtsch Med Wochenschr ; 146(20): 1337-1343, 2021 10.
Artigo em Alemão | MEDLINE | ID: mdl-34644794

RESUMO

DIAGNOSIS: The diagnosis of Graves' disease is mainly based on ultrasonography and laboratory diagnostics. This includes the determination of the TSH value and the peripheral thyroid hormones. TSH receptor antibody (TRAb) measurement is highly sensitive and specific for the detection of Graves' disease (GD) and helps to distinguish from autoimmune thyroiditis (AIT). However, as recent studies show, some may AIT patients may also reveal TRAb. THERAPY: Current guidelines recommend primarily the use of thiamazol/carbimazole in GD. Due to the comparatively higher hepatotoxicity, propylthiouracil is not recommended as first line therapy. In case of relapse during 12 up to 18 months of antithyroid drug therapy or after a frustrating attempt at cessation, definitive therapy should be considered. Alternatively, in accordance with the current recommendations of the European Thyroid Association, drug therapy may be continued for up to 12 months after initial diagnosis. PREGNANCY: The treatment of active GD during pregnancy is problematic due to diaplacental crossing of peripheral thyroid hormones, TSH receptor stimulating antibodies and antithyroid drugs. According to current guidelines, PTU is recommended during the first 16 weeks of pregnancy, whereas for the 2nd and 3 rd trimester no special recommendations are given. After that, you can choose which antithyroid drug might be used. The aim of antithyroid drug therapy during pregnancy is to achieve a suppressed TSH value together with normal or slightly increased fT4 while using lowest effective dose of antithyroid drug. IMMUNE CHECKPOINT INHIBITORS (ICI): The most common endocrine side effect with this therapy is thyroid dysfunction. Hyperthyroidism; occur most frequently in combination therapy (CTLA-4 / anti-PD-1 therapy) ICI mainly causes destructive thyroiditis with lymphocytic infiltration; GD is absolutely rare in this context and only few cases are described.


Assuntos
COVID-19/complicações , Doença de Graves/diagnóstico , Doença de Graves/terapia , Antitireóideos/efeitos adversos , Antitireóideos/uso terapêutico , Carbimazol/uso terapêutico , Causalidade , Diagnóstico Diferencial , Feminino , Doença de Graves/complicações , Doença de Graves/diagnóstico por imagem , Humanos , Metimazol/uso terapêutico , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Propiltiouracila/efeitos adversos , Propiltiouracila/uso terapêutico , Hormônios Tireóideos/análise , Tireotropina/análise , Ultrassonografia
12.
Eur J Endocrinol ; 185(4): 553-563, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34342595

RESUMO

OBJECTIVE: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. DESIGN: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. RESULTS: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). CONCLUSION: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.


Assuntos
Tecido Adiposo Marrom/metabolismo , Hipertireoidismo/metabolismo , Hipertireoidismo/reabilitação , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/efeitos dos fármacos , Adulto , Idoso , Antitireóideos/farmacologia , Antitireóideos/uso terapêutico , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Carbimazol/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Fluordesoxiglucose F18 , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Doença de Graves/reabilitação , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Metimazol/uso terapêutico , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Indução de Remissão , Singapura , Termogênese/efeitos dos fármacos , Termogênese/fisiologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologia , Adulto Jovem
13.
PLoS One ; 16(8): e0256186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34411162

RESUMO

Three new uranyl complexes [(UO2)(OAc)2(CMZ)], [(UO2)(OAc)2(MP)] and [(UO2)(OAc)2(SCZ)] were synthesized and characterized by elemental analysis, FT-IR, UV-Vis spectroscopy, powder XRD analysis, and molar conductivity. The IR analysis confirmed binding to the metal ion by the sulfur and ethoxy oxygen atoms in the carbimazole (CMZ) ligand, while in the 6-mercaptopurine (MP) ligand, the sulfur and the N7 nitrogen atom of a purine coordinated binding to the metal ion. The third ligand showed a 1:1 molar ratio and bound via sulfonamide oxygen and the nitrogen of the pyrimidine ring. Analysis of the synthesized complexes also showed that acetate groups had monodentate binding to the (UO22+). Density Functional Theory (DFT) calculations at the B3LYP level showed similar structures to the experimental results. Theoretical quantum parameters predicted the reactivity of the complexes in the order, [(UO2)(OAc)2(SCZ)] > [(UO2)(OAc)2(MP)]> [(UO2)(OAc)2(CMZ)]. DNA binding studies revealed that [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(CMZ)] have the highest binding constant (Kb) among the uranyl complexes. Additionally, strong binding of the MP and CMZ metal complexes to human serum albumin (HSA) were observed by both absorbance and fluorescence approaches. The antibacterial activity of the complexes was also evaluated against four bacterial strains: two gram-negative; Escherichia coli and Klebsiella pneumonia, and two gram-positive; Staphylococcus aureus and Streptococcus mutans. [(UO2)(OAc)2(MP)] had the greatest antibacterial activity against Klebsiella pneumonia, the gram-positive bacteria, with even higher activity than the standard antibiotic. In vitro cytotoxicity tests were also performed against three human cancer lines, and revealed the most cytotoxic complexes to be [(UO2)(OAc)2(SCZ)], which showed moderate activity against a colon cancer cell line. Thus, uranyl addition enhances the antibacterial and anticancer properties of the free ligands.


Assuntos
Carbimazol/farmacologia , Complexos de Coordenação/química , Mercaptopurina/química , Urânio/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Escherichia coli/efeitos dos fármacos , Humanos , Ligantes , Estrutura Molecular , Nitrogênio , Oxigênio/química , Albumina Sérica Humana/química , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Sulfonamidas/química
16.
J Ayub Med Coll Abbottabad ; 33(2): 244-247, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34137538

RESUMO

OBJECTIVES: To compare the efficacy of Single dose with Divided dose regimen of Carbimazole for the induction of Euthyroidism in hyperthyroid patients. METHODS: All consecutive hyperthyroidism patients from December 2018 to December 2019 fulfilling the inclusion criteria were included. They were allocated randomly into 2 groups: Group A - single dose of Carbimazole (OD-CMZ) and Group B - divided dose of Carbimazole (DD-CMZ). The therapeutic efficacy was measured at regular intervals (every 4 weeks) for 6 months. Their demographics and therapeutic management were analysed. RESULTS: Of a total of 69 (n=34 in Group A, n=35 in Group B) patients, there was no significant difference in baseline concentrations of TSH and T4 as well as their cumulative rate of reductions (p-value, 0.023). Furthermore, no difference in achieving euthyroidism was noted at follow-up visits between Group A and B respectively ([0:0%; p-value 1.00, month 1], [70.6:74.3%; p value 0.22, month 2], [85.3:85.7%; p value 0.39, month 3], 97.1:82.9%; p-value 0.23, month 4], [100:91.4%; p-value 0.29, month 5], [100:100%%; p value 1.00, month 6] at monthly intervals. Cases of Hypothyroidism were reported more in the DD-CMZ (14.3%) and the difference was statistically significant (p-value 0.003). CONCLUSIONS: Due to no significant difference in the efficacy and more chances of getting hypothyroid in divided dose regimen, we conclude that single dose regimen is more effective method for treating hyperthyroidism.


Assuntos
Antitireóideos/uso terapêutico , Carbimazol/administração & dosagem , Hipertireoidismo/tratamento farmacológico , Adulto , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
S Afr Med J ; 111(2): 176-179, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33944730

RESUMO

BACKGROUND: Radioactive iodine (RAI) is widely used in the treatment of hyperthyroidism. Adjunctive antithyroid drugs (ATDs) are commonly prescribed to treat the hyperthyroid state before the RAI has taken effect. However, there is no consensus on the use of or timing of adjunctive ATD treatment with RAI. OBJECTIVES: To determine the influence of the ATD carbimazole on the cure rate of RAI treatment for Graves' disease. METHODS: A retrospective chart review was conducted in the Department of Nuclear Medicine of the Steve Biko Academic Hospital in Pretoria. The cure rate of patients treated with RAI for Graves' disease was analysed. The effect of adjunctive carbimazole treatment with regard to its use and timing with RAI dosing was analysed. The cure rate was determined in patients treated with carbimazole either before RAI or before and after RAI administration. Cure rate was defined by the biochemical thyroid function status (thyroxine (T4), thyroid-stimulating hormone (TSH)) as euthyroid or hypothyroid from 3 months and sustained at 12 months. The need for a second dose of RAI was recorded. RESULTS: RAI treatment was administered to 171 patients with Graves' disease. The cure rate was higher in patients receiving a higher dose of RAI. The overall cure rate increased progressively from 3 months and was 91% at 12 months. The cure rate in 97 patients not receiving carbimazole was 98%. The cure rate of the 27 patients on carbimazole treatment given before RAI administration was 81%, and 73% in the 37 patients in whom it was resumed after RAI administration. The overall cure rate was lower in patients who received carbimazole (p<0.001), but especially in patients in whom carbimazole was continued after RAI administration (p<0.001). CONCLUSIONS: Adjunctive carbimazole treatment decreased the RAI cure rate of Graves' disease significantly.


Assuntos
Antitireóideos/uso terapêutico , Carbimazol/uso terapêutico , Doença de Graves/tratamento farmacológico , Radioisótopos do Iodo/uso terapêutico , Terapia Combinada , Seguimentos , Humanos , Estudos Retrospectivos , África do Sul , Neoplasias da Glândula Tireoide/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento
19.
BMJ Case Rep ; 14(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563685

RESUMO

This manuscript describes the case of a young woman, with no prior psychiatric history, who developed hypomania and paranoia as the principal presenting features of Graves' disease. After starting treatment with carbimazole and propranolol, symptoms resolved without the use of antipsychotic drugs. Close liaison between psychiatry and endocrinology services was essential. This demonstrates that treating underlying thyrotoxicosis in patients presenting with psychiatric symptoms may lead to recovery without the use of antipsychotic medication. While agitation, irritability and mood lability are well-recognised thyrotoxic symptoms, psychosis is a rare presenting feature of Graves' disease. All patients with agitation, delirium or psychiatric symptoms should have thyroid function checked as part of initial tests screening for organic disease. In new or relapsing psychiatric conditions, it is important to ask patients, their carers or relatives about symptoms of hypothyroidism or thyrotoxicosis.


Assuntos
Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Mania/etiologia , Transtornos Paranoides/etiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Antitireóideos/uso terapêutico , Carbimazol/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Doença de Graves/diagnóstico por imagem , Humanos , Propranolol/uso terapêutico
20.
BMJ Case Rep ; 14(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419752

RESUMO

Hereditary haemorrhagic telangiectasia (HHT) also known as Osler-Weber-Rendu syndrome is an autosomal dominant disorder affecting 1 in 8000 individuals. The eponym recognises the 19th-century physicians William Osler, Henri Jules Louis Marie Rendu and Frederick Parkes Weber who each independently described the disease. It is characterised by epistaxis, telangiectasia and visceral arteriovenous malformations. Individuals with HHT have been found to have abnormal plasma concentrations of transforming growth factor beta and vascular endothelial growth factor secondary to mutations in ENG, ACVRL1 and MADH4. Pulmonary artery malformations (PAVMs) are abnormal communications between pulmonary arteries and veins and are found in up to 50% of individuals with HHT. The clinical features suggestive of PAVMs are stigmata of right to left shunting such as dyspnoea, hypoxaemia, cyanosis, cerebral embolism and unexplained haemoptysis or haemothorax. The authors present the case of a 33-year-old woman presenting with progressive dyspnoea during the COVID-19 pandemic. She had a typical presentation of HHT with recurrent epistaxis, telangiectasia and pulmonary arteriovenous malformations. Although rare, PAVM should be considered in individuals presenting to the emergency department with dyspnoea and hypoxaemia. Delayed diagnosis can result in fatal embolic and haemorrhagic complications.


Assuntos
Malformações Arteriovenosas/diagnóstico , Dispneia/fisiopatologia , Epistaxe/fisiopatologia , Hipóxia/fisiopatologia , Telangiectasia Hemorrágica Hereditária/diagnóstico , Receptores de Activinas Tipo II/genética , Adulto , Antitireóideos/uso terapêutico , Malformações Arteriovenosas/fisiopatologia , Gasometria , COVID-19/diagnóstico , Carbimazol/uso terapêutico , Diagnóstico Diferencial , Feminino , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Humanos , Transtornos de Enxaqueca/complicações , Artéria Pulmonar/anormalidades , Artéria Pulmonar/diagnóstico por imagem , Veias Pulmonares/anormalidades , Veias Pulmonares/diagnóstico por imagem , SARS-CoV-2 , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/fisiopatologia , Tomografia Computadorizada por Raios X
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