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PloS One 2018Oral sensitivity to fats varies in individuals influencing nutritional status and health. Variations in oleic acid perception are associated with CD36 and odorant...
Effect of chemical interaction between oleic acid and L-Arginine on oral perception, as a function of polymorphisms of CD36 and OBPIIa and genetic ability to taste 6-n-propylthiouracil.
Oral sensitivity to fats varies in individuals influencing nutritional status and health. Variations in oleic acid perception are associated with CD36 and odorant binding protein (OBPIIa) polymorphisms, and 6-n-propylthiouracil (PROP) sensitivity, which is mediated by TAS2R38 receptor. L-Arginine (L-Arg) supplementation was shown to modify the perception of the five taste qualities. Here we analyzed the effect of three concentrations (5, 10, 15 mmol/L) of L-Arg on oral perception of oleic acid in forty-six subjects classified for PROP taster status and genotyped for TAS2R38, CD36 and OBPIIa polymorphisms. L-Arg supplementation was effective in increasing the perceived intensity of oleic acid in most subjects. The lowest concentration was the most effective, especially in PROP non-tasters or medium tasters, and in subjects with at least an allele A in CD36 and OBPIIa loci. Density Functional Theory (DFT) calculations were exploited to characterize the chemical interaction between L-Arg and oleic acid, showing that a stable 1:1 oleate·ArgH+ adduct can be formed, stabilized by a pair of hydrogen bonds. Results indicate that L-Arg, acting as a 'carrier' of fatty acids in saliva, can selectively modify taste response, and suggest that it may to be used in personalized dietetic strategies to optimize eating behaviors and health.
Topics: Adult; Arginine; CD36 Antigens; Drug Interactions; Female; Humans; Lipocalins; Male; Oleic Acid; Polymorphism, Single Nucleotide; Propylthiouracil; Quantitative Trait Loci; Receptors, G-Protein-Coupled; Taste; Taste Buds; Taste Perception; Young Adult
PubMed: 29566052
DOI: 10.1371/journal.pone.0194953 -
Nutrients Jun 2019Plant phenolics are powerful antioxidants and free radical scavengers that can contribute to the healthy functional properties of plant-based food and beverages. Thus,... (Clinical Trial)
Clinical Trial
Plant phenolics are powerful antioxidants and free radical scavengers that can contribute to the healthy functional properties of plant-based food and beverages. Thus, dietary behaviours rich in plant-based food and beverages are encouraged. However, it is well-known that the bitter taste and other low-appealing sensory properties that characterize vegetables and some other plant-based foods act as an innate barrier for their acceptance. The aim of this study was to investigate the influence of psychological traits and PROP status (the responsiveness to bitter taste of 6-n- propylthiouracil) on the choice of and familiarity with phenol-rich vegetables and beverages varying in recalled level of bitterness and astringency. Study 1 aimed at assessing the variations of the sensory properties of vegetable and coffee/tea items with two check-all-that-apply (CATA) questionnaires ( = 201 and = 188 individuals, respectively). Study 2 aimed at investigating how sensitivity to punishment, to reward, and to disgust, food neophobia, private body consciousness, alexithymia, and PROP responsiveness affect choice and familiarity with phenol-rich foods ( = 1200 individuals). A Choice Index was calculated for vegetables (CV) and coffee/tea (CC) as a mean of the choices of the more bitter/astringent option of the pairs and four Familiarity Indices were computed for vegetables (FV) and coffee/tea (FC), higher (+) or lower (-) in bitterness and astringency. Subjects higher in food neophobia, sensitivity to punishment or sensitivity to disgust reported significantly lower choice indices than individuals lower in these traits, meaning that they systematically opted for the least bitter/astringent option within the pairs. Familiarity with vegetables was lower in individuals high in sensitivity to punishment, in food neophobia and in alexithymia, irrespective of their sensory properties. The Familiarity Index with coffee/tea characterized by higher bitterness and astringency was lower in individuals high in food neophobia, sensitivity to disgust, and alexithymia. No significant effect of PROP was found on any indices. The proposed approach based on product grouping according to differences in bitterness and astringency allowed the investigation of the role of individual differences in chemosensory perception and of psychological traits as modulators of phenol-rich foods preference and consumption.
Topics: Adolescent; Adult; Age Factors; Beverages; Coffee; Diet; Female; Food Preferences; Humans; Male; Middle Aged; Phenols; Plants, Edible; Propylthiouracil; Recognition, Psychology; Taste; Tea; Vegetables; Young Adult
PubMed: 31200523
DOI: 10.3390/nu11061329 -
Endocrine Journal 2014Maternal hyperthyroidism in pregnancy is associated with adverse impacts on both mother and fetus. Recently, the American Thyroid Association and the Endocrine Society...
Maternal hyperthyroidism in pregnancy is associated with adverse impacts on both mother and fetus. Recently, the American Thyroid Association and the Endocrine Society have published guidelines for the management of thyroid diseases in pregnancy. We aimed to disclose the impact of these guidelines in current practices of Asian members of the Asia-Oceania Thyroid Association (AOTA) regarding the management of hyperthyroidism in pregnancy. Completed questionnaire survey, based on clinical case scenarios, was collected from 321 Asian physician members of AOTA from 21 Asian countries in 2013. For a woman with Graves' disease planning pregnancy, 92% of clinicians favored antithyroid treatment, 52% with propylthiouracil (PTU) while 40% preferred methimazole (MMI). For a pregnant woman with newly diagnosed overt hyperthyroidism, nearly all responders initiated PTU treatment. To monitor dosage of antithyroid drugs, approximately 73% of responders used TSH and free T4 (FT4) levels without free T3 (FT3) (53%) or with FT3 (20%). Majority of responders targeted achieving low serum TSH with FT4 (or total T4) in the upper end of the normal range. For management of gestational thyrotoxicosis, 40% chose to follow up and 52% treated patients with PTU. Although timing of TSH receptor antibodies measurement in pregnant hyperthyroid patients was variable, 53% of responders would check it at least once during pregnancy. Nearly 80% of responders do not treat subclinical hyperthyroidism in pregnancy. Therefore, despite wide variations in the management of hyperthyroidism during pregnancy in Asia, majority of Asian physicians practice within the recommendations of major professional societies.
Topics: Adult; Asia; Data Collection; Female; Humans; Hyperthyroidism; Postpartum Period; Pregnancy; Pregnancy Complications; Professional Practice; Propylthiouracil; Referral and Consultation; Surveys and Questionnaires; Thyroid Function Tests; Young Adult
PubMed: 24849535
DOI: 10.1507/endocrj.ej14-0145 -
Medicine Jul 2019Propylthiouracil (PTU) is a common antithyroid drug which can treat hyperthyroidism effectively. PTU is, however, associated to multiple adverse effects. In rare case,...
RATIONALE
Propylthiouracil (PTU) is a common antithyroid drug which can treat hyperthyroidism effectively. PTU is, however, associated to multiple adverse effects. In rare case, PTU can cause interstitial pneumonia.
PATIENT CONCERNS
A 40-year-old woman presented with dyspnea and was diagnosed with pulmonary infection at the first time. After the treatment with moxifloxacin, her symptoms still got worse.
DIAGNOSIS
The lung tissues biopsy confirmed the diagnosis of organizing pneumonia (OP) and the administration of PTU suggested the diagnosis of PTU-induced OP.
INTERVENTION
Withdrawal of PTU and the administration of methylprednisolone.
OUTCOMES
The patient's symptoms relieved significantly 1 month later and lung computed tomography (CT) scan also demonstrated significant reduction of lung lesions.
LESSONS
Here we report the first case of histologically confirmed OP induced by PTU and conduct a literature review of the cases of PTU-induced interstitial pneumonia. The awareness of PTU-induced OP can help physicians reduce the possibility of misdiagnosis.
Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Lung Diseases, Interstitial; Propylthiouracil; Tomography, X-Ray Computed
PubMed: 31277157
DOI: 10.1097/MD.0000000000016284 -
Liver Transplantation : Official... Nov 2007Severe alcoholic steatohepatitis (ASH) is the major complication of advanced alcoholic liver disease (ALD) and has a high mortality even when treated with... (Review)
Review
Severe alcoholic steatohepatitis (ASH) is the major complication of advanced alcoholic liver disease (ALD) and has a high mortality even when treated with corticosteroids. Despite the importance of reactive oxygen species in the pathophysiology of ALD and ASH, antioxidants provide no benefit in the treatment of patients with ASH. Proinflammatory cytokines are important in the pathophysiology of ALD and might mediate most of the inflammatory aspects of these disorders. New treatment modalities in ASH might involve antagonism of proinflammatory cytokines such as tumor necrosis factor (TNF) by specific antibodies or other TNF-interfering treatment strategies. Propylthiouracil and S-adenosyl methionine may be beneficial to patients with alcoholic cirrhosis, but both require further randomized, controlled trials before their use can be recommended.Liver transplantation is an effective therapy for patients with advanced alcoholic cirrhosis who have not recovered after a period of abstinence.
Topics: Adrenal Cortex Hormones; Antioxidants; Colchicine; Dietary Supplements; Humans; Liver Diseases, Alcoholic; Liver Transplantation; Pentoxifylline; Prognosis; Propylthiouracil; Temperance; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 17969070
DOI: 10.1002/lt.21336 -
Asia Pacific Journal of Clinical... 2014This study was conducted to determine the relationship between 6-n-propylthiouracil sensitivity and taste characteristics in female students at Nara Women's University....
This study was conducted to determine the relationship between 6-n-propylthiouracil sensitivity and taste characteristics in female students at Nara Women's University. Participants (n=135) were screened for 6-npropylthiouracil sensitivity using a taste test with 0.56 mM 6-n-propylthiouracil solution, and the sensitivity was confirmed by an assay for the bitter-taste receptor gene, TAS2R38. Based on the screening results, 33 6-npropylthiouracil tasters and 21 non-tasters were enrolled. The basic characteristics that are thought to influence taste acuity, including body mass index, saliva volume and serum micronutrient concentrations (iron, zinc and copper), were similar between the two groups. In an analysis using a filter-paper disc method, there were no differences in the acuity for four basic tastes (sweet, salty, sour and bitter) between 6-n-propylthiouracil tasters and non-tasters. In addition, the taste preference for the four basic tastes as measured by a visual analogue scale was also comparable between the two groups. This is the first study to demonstrate that 6-n-propylthiouracil nontasters have taste sensitivity for the four basic tastes similar to that in 6-n-propylthiouracil tasters, at least in female adolescents, as measured by the gustatory test using a filter-paper disc method.
Topics: Adolescent; Body Mass Index; Female; Food Preferences; Humans; Japan; Micronutrients; Propylthiouracil; Saliva; Taste; Young Adult
PubMed: 25164453
DOI: 10.6133/apjcn.2014.23.3.04 -
American Journal of Physiology.... Dec 2019Compounds described by humans as "bitter" are sensed by a family of type 2 taste receptors (T2Rs). Previous work suggested that diverse bitter stimuli activate distinct...
Compounds described by humans as "bitter" are sensed by a family of type 2 taste receptors (T2Rs). Previous work suggested that diverse bitter stimuli activate distinct receptors, which might allow for perceptually distinct tastes. Alternatively, it has been shown that multiple T2Rs are expressed on the same taste cell, leading to the contrary suggestion that these stimuli produce a unitary perception. Behavioral work done to address this in rodent models is limited to Spector and Kopka (Spector AC, Kopka SL. 22: 1937-1941, 2002), who demonstrated that rats cannot discriminate quinine from denatonium. Supporting this finding, it has been shown that quinine and denatonium activate overlapping T2Rs and neurons in both the mouse and rat nucleus of the solitary tract (NTS). However, cycloheximide and 6-n-propylthiouracil (PROP) do not appear to overlap with quinine in the NTS, suggesting that these stimuli may be discriminable from quinine and the denatonium/quinine comparison is not generalizable. Using the same procedure as Spector and Kopka, we tasked animals with discriminating a range of stimuli (denatonium, cycloheximide, PROP, and sucrose octaacetate) from quinine. We replicated and expanded the findings of Spector and Kopka; rats could not discriminate quinine from denatonium, cycloheximide, or PROP. Rats showed a very weak ability to discriminate between quinine and sucrose octaacetate. All animals succeeded in discriminating quinine from KCl, demonstrating they were capable of the task. These data suggest that rats cannot discriminate this suite of stimuli, although they appear distinct by physiological measures.
Topics: Animals; Cycloheximide; Dose-Response Relationship, Drug; Male; Propylthiouracil; Quaternary Ammonium Compounds; Quinine; Random Allocation; Rats; Rats, Long-Evans; Stimulation, Chemical; Sucrose; Taste
PubMed: 31596113
DOI: 10.1152/ajpregu.00213.2019 -
Endocrinology Aug 2019The CLARITY-BPA experiment, a large collaboration between the National Institute of Environmental Health Sciences, the National Toxicology Program, and the US Food and...
The CLARITY-BPA experiment, a large collaboration between the National Institute of Environmental Health Sciences, the National Toxicology Program, and the US Food and Drug Administration, is designed to test the effects of bisphenol A (BPA) on a variety of endocrine systems and end points. The specific aim of this subproject was to test the effect of BPA exposure on thyroid functions and thyroid hormone action in the developing brain. Timed-pregnant National Center for Toxicological Research Sprague-Dawley rats (strain code 23) were dosed by gavage with vehicle control (0.3% carboxymethylcellulose) or one of five doses of BPA [2.5, 25, 250, 2500, or 25,000 µg/kg body weight (bw) per day] or ethinyl estradiol (EE) at 0.05 or 0.50 µg/kg bw/d (n = 8 for each group) beginning on gestational day 6. Beginning on postnatal day (PND) 1 (day of birth is PND 0), the pups were directly gavaged with the same dose of vehicle, BPA, or EE. We also obtained a group of animals treated with 3 ppm propylthiouracil in the drinking water and an equal number of concordant controls. Neither BPA nor EE affected serum thyroid hormones or thyroid hormone‒sensitive end points in the developing brain at PND 15. In contrast, propylthiouracil (PTU) reduced serum T4 to the expected degree (80% reduction) and elevated serum TSH. Few effects of PTU were observed in the male brain and none in the female brain. As a result, it is difficult to interpret the negative effects of BPA on the thyroid in this rat strain because the thyroid system appears to respond differently from that of other rat strains.
Topics: Animals; Benzhydryl Compounds; Brain; Ethinyl Estradiol; Female; Fetus; Male; Phenols; Propylthiouracil; Rats; Rats, Sprague-Dawley; Thyroid Gland; Thyrotropin
PubMed: 31135896
DOI: 10.1210/en.2019-00121 -
Endocrine Journal Feb 2021Propylthiouracil (PTU)-induced otitis media with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is an extremely rare adverse event associated... (Review)
Review
Propylthiouracil (PTU)-induced otitis media with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is an extremely rare adverse event associated with anti-thyroid drugs and is not well recognized. A 42-year-old woman with Graves' disease undergoing PTU therapy for 8 years visited our hospital because of earache and congested feeling in her left ear. Blood tests, a computed tomography scan and pure tone audiometry revealed otitis media and moderate mixed hearing impairment. Antibiotics, ear drops with antibiotics and painkillers were administered. However, her earache and hearing loss gradually got worse and symptoms of facial nerve palsy appeared. At several weeks after initiation of the treatment, a high serum level of myeloperoxidase (MPO)-ANCA, 75.6 U/mL, was revealed. After excluding other causes, she was diagnosed with OMAAV. PTU was suspected as the cause of her OMAAV and was immediately discontinued, and prednisolone was started. Hearing impairment in her left ear gradually got better and showed substantial improvement. Facial nerve palsy disappeared. Although PTU-induced OMAAV is an extremely rare disease, it is important to recognize the disease, as delayed treatment can lead to irreversible hearing loss, hypertrophic pachymeningitis, and subarachnoid hemorrhage. When patients taking anti-thyroid drugs, especially PTU, are diagnosed with refractory otitis media or hearing loss, it is possible that OMAAV might be the cause and thus serum ANCA levels should be evaluated.
Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Female; Graves Disease; Humans; Otitis Media; Propylthiouracil
PubMed: 32999132
DOI: 10.1507/endocrj.EJ20-0184 -
Arthritis Research & Therapy Sep 2013Recent advances suggest that the cellular redox state may play a significant role in the progression of fibrosis in systemic sclerosis (SSc). Another, and as yet poorly...
INTRODUCTION
Recent advances suggest that the cellular redox state may play a significant role in the progression of fibrosis in systemic sclerosis (SSc). Another, and as yet poorly accounted for, feature of SSc is its overlap with thyroid abnormalities. Previous reports demonstrate that hypothyroidism reduces oxidant stress. The aim of this study was therefore to evaluate the effect of propylthiouracil (PTU), and of the hypothyroidism induced by it, on the development of cutaneous and pulmonary fibrosis in the oxidant stress murine model of SSc.
METHODS
Chronic oxidant stress SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl) for 6 weeks. Mice (n = 25) were randomized into three arms: HOCl (n = 10), HOCl plus PTU (n = 10) or vehicle alone (n = 5). PTU administration was initiated 30 minutes after HOCl subcutaneous injection and continued daily for 6 weeks. Skin and lung fibrosis were evaluated by histologic methods. Immunohistochemical staining for alpha-smooth muscle actin (α-SMA) in cutaneous and pulmonary tissues was performed to evaluate myofibroblast differentiation. Lung and skin concentrations of vascular endothelial growth factor (VEGF), extracellular signal-related kinase (ERK), rat sarcoma protein (Ras), Ras homolog gene family (Rho), and transforming growth factor (TGF) β were analyzed by Western blot.
RESULTS
Injections of HOCl induced cutaneous and lung fibrosis in BALB/c mice. PTU treatment prevented both dermal and pulmonary fibrosis. Myofibroblast differentiation was also inhibited by PTU in the skin and lung. The increase in cutaneous and pulmonary expression of VEGF, ERK, Ras, and Rho in mice treated with HOCl was significantly prevented in mice co-administered with PTU.
CONCLUSIONS
PTU, probably through its direct effect on reactive oxygen species or indirectly through thyroid function inhibition, prevents the development of cutaneous and pulmonary fibrosis by blocking the activation of the Ras-ERK pathway in the oxidant-stress animal model of SSc.
Topics: Actins; Animals; Antithyroid Agents; Blotting, Western; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Female; Fibrosis; Hypochlorous Acid; Hypothyroidism; Immunohistochemistry; Mice; Mice, Inbred BALB C; Muscle, Smooth; Oxidants; Propylthiouracil; Pulmonary Fibrosis; Random Allocation; Scleroderma, Systemic; Skin; Thyrotropin; Thyroxine; Triiodothyronine; Vascular Endothelial Growth Factor A; ras Proteins
PubMed: 24286160
DOI: 10.1186/ar4300