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Scientific Reports Sep 2021Larval metamorphosis in bivalves is a key event for the larva-to-juvenile transformation. Previously we have identified a thyroid hormone receptor (TR) gene that is...
Larval metamorphosis in bivalves is a key event for the larva-to-juvenile transformation. Previously we have identified a thyroid hormone receptor (TR) gene that is crucial for larvae to acquire "competence" for the metamorphic transition in the mussel Mytilus courscus (Mc). The mechanisms of thyroid signaling in bivalves are still largely unknown. In the present study, we molecularly characterized the full-length of two iodothyronine deiodinase genes (McDx and McDy). Phylogenetic analysis revealed that deiodinases of molluscs (McDy, CgDx and CgDy) and vertebrates (D2 and D3) shared a node representing an immediate common ancestor, which resembled vertebrates D1 and might suggest that McDy acquired specialized function from vertebrates D1. Anti-thyroid compounds, methimazole (MMI) and propylthiouracil (PTU), were used to investigate their effects on larval metamorphosis and juvenile development in M. coruscus. Both MMI and PTU significantly reduced larval metamorphosis in response to the metamorphosis inducer epinephrine. MMI led to shell growth retardation in a concentration-dependent manner in juveniles of M. coruscus after 4 weeks of exposure, whereas PTU had no effect on juvenile growth. It is hypothesized that exposure to MMI and PTU reduced the ability of pediveliger larvae for the metamorphic transition to respond to the inducer. The effect of MMI and PTU on larval metamorphosis and development is most likely through a hormonal signal in the mussel M. coruscus, with the implications for exploring the origins and evolution of metamorphosis.
Topics: Animals; Antithyroid Agents; Iodide Peroxidase; Larva; Metamorphosis, Biological; Methimazole; Mytilus; Propylthiouracil; Thyroid Hormones
PubMed: 34588587
DOI: 10.1038/s41598-021-98930-9 -
Birth Defects Research. Part B,... Aug 2014Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest...
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.
Topics: Animals; Antithyroid Agents; Female; Hyperthyroidism; Methimazole; Mice; Mice, Inbred C57BL; Pregnancy; Pregnancy Complications; Propylthiouracil; Rats; Rats, Sprague-Dawley; Teratogens
PubMed: 24980470
DOI: 10.1002/bdrb.21113 -
The Western Journal of Medicine May 1977Propylthiouracil and methimazole are used widely in the treatment of hyperthyroid disorders. The most important complication of the use of these drugs is depression of...
Propylthiouracil and methimazole are used widely in the treatment of hyperthyroid disorders. The most important complication of the use of these drugs is depression of the neutrophilic granulocyte count. Granulocytopenia occurs in about 4 percent and agranulocytosis occurs in about 0.3 percent of treated patients. Although this depression of the granulocyte count is reversible after the drug is discontinued, serious infection frequently accompanies agranulocytosis and accounts for almost all deaths related to the drugs. It is important to be aware of the clinical features of granulocytopenic reactions due to antithyroid drugs.
Topics: Agranulocytosis; Humans; Hypothyroidism; Methimazole; Propylthiouracil
PubMed: 867981
DOI: No ID Found -
Chemical Senses Sep 2018TAS2R38 gene variants, which confer sensitivity to specific bitter tastants (e.g., 6-n-propylthiouracil), have been repeatedly associated with lower alcohol use via...
TAS2R38 gene variants, which confer sensitivity to specific bitter tastants (e.g., 6-n-propylthiouracil), have been repeatedly associated with lower alcohol use via greater bitterness perception, but research exploring TAS2R38 variation in relation to smoking shows mixed results. In both, the working hypothesis is that 1 or more copies of the functional allele increases bitterness and may provide a barrier to early use. Such a barrier to initiation may, conceivably, manifest as differential rates of current use across diplotypes. Here, an age-diverse convenience sample (n = 886) of Denver Museum of Nature and Science guests was used to explore cross-sectional relationships between TAS2R38 diplotype, self-reported tobacco use (current, former, never smokers), and a rapid measure of 6-n-propylthiouracil phenotype (bitterness of filter paper discs). TAS2R38 diplotypes were determined by Sanger sequencing. After excluding rare diplotypes, data from 814 participants were analyzed. A mix of current (~10%), former (25%), and never smokers (65%) were included. As expected, there was a relationship between TAS2R38 diplotype and 6-n-propylthiouracil bitterness. However, contrary to our hypothesis, there was no evidence of a relationship between diplotype and smoker status among participants with common TAS2R38 diplotypes. Notably, we observed a relationship between of 6-n-propylthiouracil bitterness and smoking status, but the effect was opposite of what was expected: current smokers perceived higher (not lower) bitterness than never smokers. When all the various factors (diplotype, age, sex, and smoking status) were included in ANOVA, all remained predictive of 6-n-propylthiouracil bitterness. Reasons for greater phenotypic bitterness among current smokers are unknown and merit further study.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cohort Studies; Cross-Sectional Studies; Crowdsourcing; Female; Humans; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Propylthiouracil; Receptors, G-Protein-Coupled; Self Report; Smoking; Young Adult
PubMed: 30137252
DOI: 10.1093/chemse/bjy053 -
Thyroid : Official Journal of the... Nov 2020Thionamides have been extensively used to treat patients with hyperthyroidism worldwide. Recent pharmacovigilance studies have revealed a safety signal between...
Thionamides have been extensively used to treat patients with hyperthyroidism worldwide. Recent pharmacovigilance studies have revealed a safety signal between carbimazole or methimazole and pancreatitis. The associated risk remains unclear. We identified patients with newly diagnosed acute pancreatitis from 2000 to 2013 as the case group from the Taiwan Longitudinal Health Insurance Database 2000, which contains data from 1996 to 2013. Each patient with acute pancreatitis was matched for age, sex, comorbidities, and cancer with four controls through propensity score matching. A total of 52 patients without matched controls were excluded. Sensitivity analyses including the 52 excluded patients were performed using a matching ratio of 1:2. Odds ratios (ORs) along with 95% confidence intervals (CIs) for the association were estimated using multivariate logistic regression. We included 9204 and 36,816 patients in the case and control groups, respectively. The proportions of patients who had used thionamides, carbimazole, methimazole, and propylthiouracil were similar in these two groups. In addition, the adjusted OR (CI) for the association of acute pancreatitis with thionamides was 1.03 (0.86-1.24), with carbimazole it was 0.90 (0.63-1.30), with methimazole it was 1.05 (0.84-1.31), and with propylthiouracil it was 1.00 (0.74-1.34). The sensitivity analysis results were unchanged. We were unable to demonstrate an association between acute pancreatitis and usage of thionamides.
Topics: Adult; Aged; Antithyroid Agents; Carbimazole; Case-Control Studies; Comorbidity; Databases, Factual; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Multivariate Analysis; Odds Ratio; Pancreatitis; Pharmacovigilance; Propylthiouracil; Retrospective Studies; Risk; Taiwan; Thioamides
PubMed: 32380933
DOI: 10.1089/thy.2019.0589 -
Nutrients Aug 2014Taste sensitivity to the bitter compound 6-n-propylthiouracil (PROP) is considered a marker for individual differences in taste perception that may influence food... (Review)
Review
Taste sensitivity to the bitter compound 6-n-propylthiouracil (PROP) is considered a marker for individual differences in taste perception that may influence food preferences and eating behavior, and thereby energy metabolism. This review describes genetic factors that may contribute to PROP sensitivity including: (1) the variants of the TAS2R38 bitter receptor with their different affinities for the stimulus; (2) the gene that controls the gustin protein that acts as a salivary trophic factor for fungiform taste papillae; and (3) other specific salivary proteins that could be involved in facilitating the binding of the PROP molecule with its receptor. In addition, we speculate on the influence of taste sensitivity on energy metabolism, possibly via modulation of the endocannabinoid system, and its possible role in regulating body composition homeostasis.
Topics: Body Composition; Body Mass Index; Diet; Energy Metabolism; Feeding Behavior; Food Preferences; Humans; Obesity; Propylthiouracil; Receptors, Cannabinoid; Taste Buds; Taste Perception; Taste Threshold
PubMed: 25166026
DOI: 10.3390/nu6093363 -
Physiology & Behavior Mar 2019Chronic cigarette smoking may influence chemosensory function, which in turn, may affect cigarette usage. Because menthol in cigarettes can attenuate nicotine...
Chronic cigarette smoking may influence chemosensory function, which in turn, may affect cigarette usage. Because menthol in cigarettes can attenuate nicotine bitterness, choice of menthol/nonmenthol cigarettes may be influenced by ability to perceive bitterness. We examined chemosensory function of chronic smokers, hypothesizing they would show altered function in comparison to non-smokers and by menthol cigarette preference. In laboratory-based measures, chronic smokers (N = 135; 84 menthol smokers) self-reported their chemosensory function and participated in smell (identification task with perceived intensity) and taste (quinine and NaCl intensity on tongue-tip and whole mouth) testing. A taste genetics probe (propylthiouracil (PROP) bitterness) also was assessed. Self-reported and measured chemosensory function were compared with nationally-representative 2013-2014 National Health and Nutrition Examination Survey (NHANES) data generated with similar measures. The taste measures also were compared between smokers and age- and sex-matched non-smokers from a laboratory database. Frequencies of self-reported smell and taste alterations among smokers exceeded NHANES prevalence estimates for non-smokers. The rate of measured smell dysfunction also exceeded NHANES prevalence for hyposmia. Compared to non-smokers, smokers reported elevated tongue-tip and whole mouth intensities from 1 M NaCl, with no significant differences in whole mouth quinine or 0.32 M NaCl. Inconsistent with previous hypotheses, smokers were not more likely to report depressed PROP bitterness than non-smokers. However, as expected, menthol smokers reported greater PROP bitterness than non-menthol smokers. In conclusion, chemosensory alterations were more frequent among chronic smokers, including hyposmia and heightened intensity from NaCl at an oral-irritant concentration. PROP supertasters were most likely to prefer mentholated cigarettes.
Topics: Adolescent; Adult; Female; Humans; Male; Menthol; Middle Aged; Mouth Diseases; Olfaction Disorders; Propylthiouracil; Quinine; Self Report; Sensation; Smoking; Sodium Chloride; Taste; Taste Disorders; Young Adult
PubMed: 30557565
DOI: 10.1016/j.physbeh.2018.12.017 -
Ugeskrift For Laeger Sep 2014The treatment of choice for hyperthyroidism in pregnancy is antithyroid drugs, but the potential risk of birth defects is of major concern. For the use of thiamazole and... (Review)
Review
The treatment of choice for hyperthyroidism in pregnancy is antithyroid drugs, but the potential risk of birth defects is of major concern. For the use of thiamazole and carbimazole, there is consistent evidence of an increased risk of birth defects, which are often severe. For the use of propylthiouracil, the evidence is less clear. These birth defects may be less severe, and a Danish study which included all birth defects diagnosed before the age of two years showed an increased risk of birth defects in the face and neck region and in the urinary system after the use of propylthouracil.
Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Propylthiouracil; Risk Factors
PubMed: 25294327
DOI: No ID Found -
International Dental Journal Dec 2022Bitter taste perception and sweetness preference have been associated with dental caries. Propylthiouracil (PROP) has been used to determine the genetic sensitivity to...
BACKGROUND
Bitter taste perception and sweetness preference have been associated with dental caries. Propylthiouracil (PROP) has been used to determine the genetic sensitivity to bitter taste in early childhood caries. However, the role of the bitter threshold in dental biofilm cariogenicity has not been reported. The purpose of this study was to investigate the role of individual taste sensitivity using PROP in dental biofilm cariogenicity in orthodontic patients.
METHODS
Forty orthodontic patients (12-42 years old) undergoing fixed appliance orthodontic treatment participated in this cross-sectional study. Their demographic, oral hygiene practice, and dietary habits data were obtained using a questionnaire. The patients' bitter taste threshold was measured using a PROP assay. The patients were subsequently classified as super-tasters (STs), medium-tasters (MTs), and non-tasters (NTs). Dental biofilm cariogenicity was determined using a 3-tone disclosing gel that becomes pink (new dental biofilm), purple (mature dental biofilm), and light blue (cariogenic dental biofilm) based on dental biofilm maturity.
RESULTS
The NT, MT, and ST groups comprised 10%, 27.5%, and 62.5% of the patients, respectively. Most of the STs (56%) and MTs (63.6%) were female, whereas no females were NTs. The dental biofilm cariogenicity was significantly different between the PROP bitterness groups (P < .05). The highest percentage of mature biofilm, followed by cariogenic and new biofilm, was found in the MT and ST groups. However, the cariogenic biofilm percentage was significantly higher compared with mature biofilm (P < .05) in the NT group. A low frequency (<1 time/d) of sugary and acidic food intake between meals was observed in the ST, MT, and NT groups with no significant difference amongst the groups (P > .05).
CONCLUSIONS
Cariogenic dental biofilm was highly present in orthodontic patients with the NT phenotype.
Topics: Child, Preschool; Humans; Taste Perception; Dental Caries; Cross-Sectional Studies; Taste; Propylthiouracil; Biofilms; Food Preferences
PubMed: 35961845
DOI: 10.1016/j.identj.2022.07.003 -
CMAJ : Canadian Medical Association... Jan 1987Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated... (Review)
Review
Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful.
Topics: Adult; Agranulocytosis; Antibody Formation; Cross Reactions; Drug Hypersensitivity; Female; Graves Disease; Humans; Hyperthyroidism; Immunity, Cellular; Methimazole; Middle Aged; Propylthiouracil
PubMed: 3539299
DOI: No ID Found