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Journal of Complementary & Integrative... Mar 2024This study aimed to investigate the antioxidant effect of rosiglitazone (ROG) and pioglitazone (POG) on oxidative damage and dysfunction of hepatic tissue in hypothyroid...
OBJECTIVES
This study aimed to investigate the antioxidant effect of rosiglitazone (ROG) and pioglitazone (POG) on oxidative damage and dysfunction of hepatic tissue in hypothyroid rats.
METHODS
The male rats were classified into six groups: (1) Control; (2) Hypothyroid, (3) Hypothyroid-POG 10, (4) Hypothyroid-POG 20, (5) Hypothyroid-ROG 2, and (6) Hypothyroid-ROG 4. To induction hypothyroidism in rats, propylthiouracil (PTU) (0.05 %w/v) was added to drinking water. In groups 2-6, besides PTU, the rats were also intraperitoneal administrated with 10 or 20 mg/kg POG or 2 or 4 mg/kg ROG for six weeks. Finally, after deep anesthesia, the blood was collected to measure the serum biochemical markers and hepatic tissue was separated for biochemical oxidative stress markers.
RESULTS
Administration of PTU significantly reduced serum thyroxin concentration, total thiol levels, activity of superoxide dismutase (SOD) and catalase (CAT) enzymes, and increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (Alk-P) and malondialdehyde (MDA) in the liver. Additionally, our results showed that prescription of POG or ROG for six weeks to hypothyroid rats resulted in an improvement in liver dysfunction (decrease in serum levels of AST, ALT, and ALK-P) through reducing oxidative damage in hepatic tissue (increase in CAT, SOD, or total thiols and decrease in MDA levels).
CONCLUSIONS
The findings of the present study presented that the IP administration of POG and ROG for six weeks improves liver dysfunction induced by hypothyroidism in juvenile rats by reducing oxidative damage.
Topics: Rats; Animals; Male; Pioglitazone; Rosiglitazone; Rats, Wistar; Hypothyroidism; Antioxidants; Oxidative Stress; Propylthiouracil; Superoxide Dismutase; Liver; Liver Diseases; Receptor Protein-Tyrosine Kinases
PubMed: 38253264
DOI: 10.1515/jcim-2023-0147 -
Computational and Structural... 2023Several studies were focused on the genetic ability to taste the bitter compound 6-n-propylthiouracil (PROP) to assess the inter-individual taste variability in humans,...
Several studies were focused on the genetic ability to taste the bitter compound 6-n-propylthiouracil (PROP) to assess the inter-individual taste variability in humans, and its effect on food predilections, nutrition, and health. PROP taste sensitivity and that of other chemical molecules throughout the body are mediated by the bitter receptor TAS2R38, and their variability is significantly associated with genetic variants. We recently automatically identified PROP phenotypes with high precision using Machine Learning (mL). Here we have used Supervised Learning (SL) algorithms to automatically identify genotypes by using the biological features of eighty-four participants. The catBoost algorithm was the best-suited model for the automatic discrimination of the genotypes. It allowed us to automatically predict the identification of genotypes and precisely define the effectiveness and impact of each feature. The ratings of perceived intensity for PROP solutions (0.32 and 0.032 mM) and medium taster (MT) category were the most important features in training the model and understanding the difference between genotypes. Our findings suggest that SL may represent a trustworthy and objective tool for identifying TAS2R38 variants which, reducing the costs and times of molecular analysis, can find wide application in taste physiology and medicine studies.
PubMed: 38213886
DOI: 10.1016/j.csbj.2023.01.029 -
Cardiovascular Endocrinology &... Mar 2024Myocarditis due to Graves` disease is rare and has a clinical presentation that mimics acute coronary syndrome. In this case report, a 50-year-old woman was admitted...
Myocarditis due to Graves` disease is rare and has a clinical presentation that mimics acute coronary syndrome. In this case report, a 50-year-old woman was admitted with a clinical presentation of very high-risk non-ST segment elevation myocardial infarction, new-onset atrial fibrillation, and acute heart failure. Normal coronary angiography and the presence of intra-myocardial late gadolinium enhancement based on cardiac MRI led to the diagnosis of myocarditis. The presence of thyroid nodules and elevated thyrotropin receptor antibodies indicated Graves` disease as the underlying cause of myocarditis. Management using Propylthiouracil and the guideline-directed medical therapy for heart failure successfully improved the patient's condition. Early diagnosis, effective care, and adequate knowledge of the relationship between hyperthyroidism and myocarditis, improve outcomes in Graves' disease-induced myocarditis.
PubMed: 38213667
DOI: 10.1097/XCE.0000000000000297 -
The Journal of Maternal-fetal &... Dec 2024To assess pre-term birth, low birth-weight and growth restriction according to maternal thyroid screening results and subsequent treatment.
OBJECTIVE
To assess pre-term birth, low birth-weight and growth restriction according to maternal thyroid screening results and subsequent treatment.
METHODS
This is a nonintervention nested case-control study derived from 10,052 asymptomatic women previously screened during the first trimester marker with anti-thyroid peroxidase antibodies, serum thyroid stimulating hormone, and free thyroxine. Screening results had been classified as positive with one or more markers outside the normal range and referred to an endocrinologist. Cases were 512 women with positive results and information on recommended treatment: 204 thyroxine, propylthiouracil or surgery, and 308 no treatment or only iodine. Controls were a sequential sample of 1292 women with negative results. All cases and controls had information on gestation at delivery or birth-weight. Outcome measures were pre-term birth (<37 weeks), low birth-weight (<2.5 kg) and, for singletons, small for gestational age (SGA; <10th percentile).
RESULTS
Among singleton pregnancies, there was a higher prevalence of both pre-term birth (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.21-2.36, < .002) and low birth-weight (RR 1.72, 95% CI 1.13-2.62, < .02) in cases compared with controls. An increase in low birth-weight was also present in term pregnancies, but not significant (RR 1.80, 95% CI 0.78-4.14, = .16), and there was no difference in SGA prevalence (1.24, 95% CI 0.93-1.65, = .14). Among cases there was no significant difference in these rates according to treatment even after logistic regression, allowing for the individual screening marker levels and maternal weight.
CONCLUSIONS
Women with positive thyroid screening results are at increased risk of pre-term birth regardless of thyroid dysfunction or subsequent treatment. An association with low birth-weight is probably secondary to early delivery.
Topics: Pregnancy; Female; Humans; Thyroid Gland; Thyroxine; Case-Control Studies; Term Birth; Prenatal Diagnosis
PubMed: 38191240
DOI: 10.1080/14767058.2023.2300416 -
Graves' Disease Exacerbation with Impending Thyroid Storm After SARS-CoV-2 Infection: A Case Report.The American Journal of Case Reports Jan 2024BACKGROUND Since the COVID-19 pandemic, several cases of COVID-19 have been linked to the development of autoimmune disorders, including of the thyroid. Graves' disease...
BACKGROUND Since the COVID-19 pandemic, several cases of COVID-19 have been linked to the development of autoimmune disorders, including of the thyroid. Graves' disease (GD) is a rare complication that can occur following SARS-CoV-2 infection. Reports have linked COVID-19 to new onset and exacerbation of GD. We present a case of a 42-year-old woman with a history of GD presenting with impending thyroid storm 3 weeks following a diagnosis of COVID-19. CASE REPORT A 42-year-old woman with a history of GD presented to the Emergency Department (ED) for an acute exacerbation of hyperthyroidism 3 weeks after SARS-CoV-2 infection was diagnosed on a home test. Symptoms included daily headaches, increased bilateral eye pressure, fatigue, muscle weakness, episodes of confusion and agitation, persistent heart palpitations, and goiter. Elevated free T4 of 5.57, free T3 of 15.68, total T3 of 4.43, and near-absent thyroid stimulating hormone were noted. The Burch-Wartofsky scale was 40, which was concerning for an impending thyroid storm; however, at the time of admission, she was not in a thyroid storm. Treatment included propylthiouracil, potassium iodide oral solution, and propranolol, with symptom improvement. Due to prior history of intolerance to antithyroid medications and recent exacerbation, a thyroidectomy was performed once she was in a euthyroid state. CONCLUSIONS Our case demonstrates the importance of recognizing COVID-19 as an etiology or a trigger for new onset or exacerbation of GD. Our case highlights that being vigilant to recognize the association between COVID-19 and thyroid abnormalities for early diagnosis and treatment is imperative.
Topics: Female; Humans; Adult; Thyroid Crisis; Pandemics; COVID-19; SARS-CoV-2; Graves Disease
PubMed: 38184779
DOI: 10.12659/AJCR.941311 -
Journal of the Endocrine Society Dec 2023Antithyroid drugs (ATDs) are the cornerstone of hyperthyroidism management. Hepatotoxicity due to ATDs can range from mild transaminase elevation to liver... (Review)
Review
CONTEXT
Antithyroid drugs (ATDs) are the cornerstone of hyperthyroidism management. Hepatotoxicity due to ATDs can range from mild transaminase elevation to liver transplantation requirement and mortality.
OBJECTIVE
The primary objective of the systematic review was to assess the clinical characteristics and outcomes of patients with drug induced liver injury (DILI) due to ATDs.
METHODS
We conducted a systematic review of PUBMED, SCOPUS, and EMBASE on characteristics and outcomes of adults (>18 years) with DILI due to ATDs. We defined DILI as bilirubin ≥2.5 mg/dL or international normalized ratio >1.5 with any rise in alanine aminotransferase (ALT), aminotransferase (AST), or alkaline phosphatase (ALP), or an elevation of ALT or AST >5 times or ALP >2 times the upper limit of normal without jaundice/coagulopathy.
RESULTS
The review included 100 articles describing 271 patients; 148 (70.8%) were female (N = 209). Mean age was 42.9 ± 17.2 years. Graves' disease was the most common indication for ATDs. Carbimazole/methimazole (CBM/MMI) was the most common offending agent (55.7%). DILI pattern was hepatocellular in 41.8%, cholestatic in 41.3%, and mixed in 16.9%. Outcomes included death in 11.8%, liver transplantation in 6.4%, partial improvement in 2.2%, and complete resolution in 79.6% with a median time (IQR) to resolution of 45 (20-90) days. Patients in the propylthiouracil (PTU) group had higher initial bilirubin, initial AST, initial ALT, peak ALT, peak AST, severe and fatal DILI, liver transplantation, and mortality than CBM/MMI. Rechallenge of antithyroid medication was infrequently reported (n = 16) but was successful in 75%.
CONCLUSION
DILI due to ATDs can present with different patterns and should prompt immediate drug discontinuation. Referral to a hepatologist should be considered if severe as transplantation is sometimes required. PTU-induced DILI may have worse outcomes than CBM/MMI.
PubMed: 38178906
DOI: 10.1210/jendso/bvad133 -
International Journal of Clinical... 2023To evaluate the association between severe early childhood caries (S-ECC), dietary preferences, and 2nd digit-4th digit (2D:4D) ratio. The objective is to contrast the...
BACKGROUND AND AIM
To evaluate the association between severe early childhood caries (S-ECC), dietary preferences, and 2nd digit-4th digit (2D:4D) ratio. The objective is to contrast the detection and prevalence of dental caries in children with different sensitivity levels to the bitter taste of 6--propylthiouracil (PROP) and its association with 2D:4D.
MATERIALS AND METHODS
A total of 300 children below 71 months of age were assigned to two study groups-group I (caries-free) and group II (caries). PROP sensitivity test was carried out to determine the inherent genetic ability to taste a bitter or sweet substance. Evaluation of dietary preferences was carried out using a food preference questionnaire, which was completed by the parents of the children to know the child's dietary habits and their sweet, sour, and strong taste preferences. The length of the index (2D) and ring (4D) finger was measured with the help of digital vernier caliper to record the 2D:4D ratio. The data obtained was subjected to statistical analysis using Pearson's Chi-squared test and one-way analysis of variance (ANOVA).
RESULTS
The results suggested a positive association between S-ECC and dietary preferences but could not establish a straightforward 1:1 relation between 2D:4D ratio and S-ECC.
CONCLUSION
An individual considered as nontaster by PROP test was a sweet liker with low 2D:4D ratio having high caries index. The association between 2D:4D ratio and S-ECC should further be explored by taking other influencing factors into consideration before arriving at a definitive conclusion.
HOW TO CITE THIS ARTICLE
Srivastava SK, Garg N, Pathivada L, Association between Severe Early Childhood Caries, Dietary Preferences, and 2nd Digit-4th Digit (2D:4D) Ratio. Int J Clin Pediatr Dent 2023;16(5):740-744.
PubMed: 38162242
DOI: 10.5005/jp-journals-10005-2681 -
Environmental Science & Technology Jan 2024Identifying endocrine disrupting chemicals in order to limit their usage is a priority and required according to the European Regulation. There are no Organization for...
Identifying endocrine disrupting chemicals in order to limit their usage is a priority and required according to the European Regulation. There are no Organization for Economic Co-operation and Development (OECD) test guidelines based on fish available for the detection of Thyroid axis Active Chemicals (TACs). This study aimed to fill this gap by developing an assay at eleuthero-embryonic life stages in a novel medaka () transgenic line. This transgenic line expresses green fluorescent protein (GFP) in thyrocytes, under the control of the medaka gene promoter. The fluorescence expressed in the thyrocytes is inversely proportional to the thyroid axis activity. When exposed for 72 h to activators (triiodothyronine (T) and thyroxine (T)) or inhibitors (6--propylthiouracil (PTU), Tetrabromobisphenol A (TBBPA)) of the thyroid axis, the thyrocytes can change their size and express lower or higher levels of fluorescence, respectively. This reflects the regulation of thyroglobulin by the negative feedback loop of the Hypothalamic-Pituitary-Thyroid axis. T, T, PTU, and TBBPA induced fluorescence changes with the lowest observable effect concentrations (LOECs) of 5 μg/L, 1 μg/L, 8 mg/L, and 5 mg/L, respectively. This promising tool could be used as a rapid screening assay and also to help decipher the mechanisms by which TACs can disrupt the thyroid axis in medaka.
Topics: Animals; Thyroid Gland; Oryzias; Thyroglobulin; Triiodothyronine
PubMed: 38117130
DOI: 10.1021/acs.est.3c05515 -
JCEM Case Reports Nov 2023Hyperthyroidism due to gestational trophoblastic disease (GTD) is a rare but potentially life-threatening condition. Optimal perioperative management is crucial for...
Hyperthyroidism due to gestational trophoblastic disease (GTD) is a rare but potentially life-threatening condition. Optimal perioperative management is crucial for favorable outcomes and prevention of thyroid storm. However, scarce data exist defining the ideal approach to this complex clinical presentation. This case report describes a first-time pregnant 32-year-old woman who was found to be biochemically hyperthyroid in the context of a 10-week gestation molar pregnancy. Despite her biochemical values, the patient remained clinically asymptomatic of her thyroid disease. The Gynecology and Anesthesiology services urgently consulted Endocrinology, and empiric treatment for prevention of potential impending thyroid storm was initiated prior to operative uterine evacuation. After 2 uneventful dilation and curettages with chemotherapy and a transient prescription of antithyroid medication, the patient normalized her human chorionic gonadotropin (hCG) level and recovered to biochemical euthyroidism. Other than a pruritic rash that may have been due to propylthiouracil, the patient's hyperthyroidism improved without further complications. This case highlights the importance of recognizing the link between GTD and thyrotoxicosis to allow for timely initiation of appropriate preoperative treatment. Fortunately, the multidisciplinary approach facilitated management to prevent evolution to thyroid storm.
PubMed: 38077310
DOI: 10.1210/jcemcr/luad129 -
Toxicological Sciences : An Official... Feb 2024Evaluating the neurodevelopmental effects of thyroid-disrupting chemicals is challenging. Although some standardized developmental and reproductive toxicity studies...
Evaluating the neurodevelopmental effects of thyroid-disrupting chemicals is challenging. Although some standardized developmental and reproductive toxicity studies recommend serum thyroxine (T4) measures in developing rats, extrapolating between a serum T4 reduction and neurodevelopmental outcomes is not straightforward. Previously, we showed that the blood-brain and blood-cerebrospinal fluid barriers may be affected by developmental hypothyroidism in newborn rats. Here, we hypothesized that if the brain barriers were functionally disturbed by abnormal thyroid action, then small molecules may escape from the brain tissue and into general circulation. These small molecules could then be identified in blood samples, serving as a direct readout of thyroid-mediated developmental neurotoxicity. To address these hypotheses, pregnant rats were exposed to propylthiouracil (PTU, 0 or 3 ppm) to induce thyroid hormone insufficiency, and dams were permitted to give birth. PTU significantly reduced serum T4 in postnatal offspring. Consistent with our hypothesis, we show that tight junctions of the brain barriers were abnormal in PTU-exposed pups, and the blood-brain barrier exhibited increased permeability. Next, we performed serum microRNA Sequencing (miRNA-Seq) to identify noncoding RNAs that may reflect these neurodevelopmental disturbances. Of the differentially expressed miRNAs identified, 7 were upregulated in PTU-exposed pups. Validation by qRT-PCR shows that miR-495 and miR-543-3p were similarly upregulated in males and females. Interestingly, these miRNAs have been linked to cell junction dysfunction in other models, paralleling the identified abnormalities in the rat brain. Taken together, these data show that miR-495 and miR-543-3p may be novel in vivo biomarkers of thyroid-mediated developmental neurotoxicity.
Topics: Animals; Female; Male; Pregnancy; Rats; Brain; Hypothyroidism; MicroRNAs; Neurotoxicity Syndromes; Thyroid Hormones; Thyroxine; Up-Regulation
PubMed: 38070162
DOI: 10.1093/toxsci/kfad125