Literatura científica selecionada sobre o tema "DEHAL-1"

Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide in the human thyroid. The aim of the present study was (I) to investigate whether DEHAL1 expression is different in differentially functioning thyroid pathologies and (II) to evaluate DEHAL1 as a possible marker of thyroid cell differentiation. Design and methods: Real-time PCR for DEHAL1 and its isoform DEHAL1B was performed in a series of 105 thyroid specimens, including toxic thyroid nodules (TTN), Graves’ disease (GD) thyroids, benign cold thyroid nodules (CTN), normal thyroid tissues and thyroid cancers (follicular thyroid carcinomas (FTC), papillary thyroid carcinomas (PTC), partially differentiated thyroid cancers (PDTC) and anaplastic thyroid carcinomas (ATC)). In addition, DEHAL1 protein expression was studied by immunohistochemistry in 163 benign and malignant thyroid pathologies and normal thyroids. Results: (I) The highest DEHAL1 mRNA levels were found in GD thyroids, while downregulation of DEHAL1 and DEHAL1B mRNA occurred in PTC and ATC (P<0.001 and <0.05 respectively); (II) DEHAL1 protein was overexpressed in TTNs and GD thyroids with predominant apical staining in all samples; (III) a weaker and patchy staining pattern was found in CTNs and normal thyroids; (IV) in differentiated thyroid cancers (FTC and PTC), a diffuse cytoplasmic DEHAL1 expression was found; and (V) in PDTC and ATC, DEHAL1 expression was faint or absent. Conclusion: Upregulation of DEHAL1 protein expression and sublocalisation of DEHAL1 at the apical cell pole in TTNs and GD thyroids is consistent with increased thyroid hormone turnover during thyrotoxicosis. Diffuse cytoplasmatic localisation or downregulation of DEHAL1 expression in thyroid cancers suggests alteration or loss of DEHAL1 function during thyroid cell dedifferentiation.

Plasticizers can persist during the treatment of wastewaters in sewage treatment plants (STPs) and can be discharged in effluents and/or accumulated in sewage sludges. For example, di-2-ethylhexyl phthalate (DEHP) is a common plasticizer that is now considered a priority pollutant and is known to accumulate in sludges. This may add constraints to the exploitation of the beneficial uses of sludges that contain significant quantities of plasticizers. Recently, it was demonstrated in studies with pure cultures that the biodegradation of plasticizers including DEHP and di-ethylhexyl adipate (DEHA) generates toxic metabolites including 2-ethylhexanoic acid, 2-ethylhexanol, and 2-ethylhexanal. However, the environmental impacts and fate of the degradation products arising from plasticizers are unknown. Therefore, this work investigated the concentrations of DEHP and DEHA and their metabolites in the sludges from several STPs in Quebec, Canada. DEHP and DEHA were found in concentrations ranging from 15 to 346 mg kg−1 and 4 to 743 mg kg−1, respectively, in primary, secondary, digested, dewatered or dried sludges. Metabolites were detected in almost all sludges, except those that had undergone a drying process at high temperature. It is concluded that sludges can represent significant sources of plasticizers and their toxic metabolites in the environment.

Residential dust is recognized as a major source of environmental contaminants, including polycyclic aromatic hydrocarbons (PAHs) and plasticizers, such as phthalic acid esters (PAEs). A sampling campaign was carried out to characterize the dust fraction of particulate matter with an aerodynamic diameter smaller than 10 µm (PM10), using an in situ resuspension chamber in three rooms (kitchen, living room, and bedroom) of four Spanish houses. Two samples per room were collected with, at least, a one-week interval. The PM10 samples were analyzed for their carbonaceous content by a thermo-optical technique and, after solvent extraction, for 20 PAHs, 8 PAEs and one non-phthalate plasticizer (DEHA) by gas chromatography-mass spectrometry. In general, higher dust loads were observed for parquet flooring as compared with tile. The highest dust loads were obtained for rugs. Total carbon accounted for 9.3 to 51 wt% of the PM10 mass. Plasticizer mass fractions varied from 5 µg g−1 to 17 mg g−1 PM10, whereas lower contributions were registered for PAHs (0.98 to 116 µg g−1). The plasticizer and PAH daily intakes for children and adults via dust ingestion were estimated to be three to four orders of magnitude higher than those via inhalation and dermal contact. The thoracic fraction of household dust was estimated to contribute to an excess of 7.2 to 14 per million people new cancer cases, which exceeds the acceptable risk of one per million.

<p>An investigation was carried out at Deha Tea Estate, Jorhat, Assam during 2015-16 by using different indigenous technical<br />knowledge (ITK) prevalent among different small tea growers. Fish extract at (0.25, 0.5 and 1%), Polygonum hydropiper at (2.5,<br />5 and 7.5%) and Azadirachtin (Neemazal-F 5%) were evaluated in field conditions against tea mite. The result showed that fish<br />extract in combination with cow dung, cow urine and water when sprayed at one per cent concentration, significantly reduced red<br />spider mite population (96.5%), percentage of leaves infestation (5.2%) and leaf area infested by the mite (11.6%). P. hydropiper<br />in combination with cow urine and water when sprayed at 7.5 per cent concentration significantly reduced red spider mite<br />population (87.5%), percentage of infestation (9.1%) and leaf area infested by the mite (12.9%). Among all the ITKs, fish extract<br />at one per cent caused higher reduction of infestation of red spider mite followed by P. hydropiper extract at 7.5 per cent.<br />Influence of both the treatments on the management of red spider mite was at par with that of commercial Azadirachtin.</p>

In this work, Chromabond® HLB was evaluated as an extraction sorbent of a group of seven phthalic acid esters (PAEs; i.e., dipropyl phthalate, DPP, dibutyl phthalate, DBP, diisopentyl phthalate, DIPP, di-n-pentyl phthalate, DNPP, butylbenzyl phthalate, BBP, dicyclohexyl phthalate, DCHP, and di(2-ethylhexyl)phthalate, DEHP) and one adipate (di(2-ethylhexyl) adipate, DEHA) from tap and waste water prior to gas chromatography-mass spectrometry. After the optimization of the extraction conditions (200 mg of sorbent conditioned with 10 mL of acetonitrile and 2 mL of Milli-Q water, extraction of 50 mL of water at pH 6.0, vacuum drying for 20 min and elution with 10 mL of ethyl acetate), a recovery study was developed at different concentration levels in each matrix, which revealed that most of the target analytes could be recovered between 75 and 112%, with relative standard deviation values for all of them below 20%. Matrix effect was evaluated, finding that matrix-matched calibration should be developed for most analytes in both matrices. The limits of quantification (LOQs) of the method were in the 0.82–71 ng L−1 range. The developed method was also applied to the extraction of the target PAEs in different water samples finding some of them, in particular, DNPP in tap water samples, and BBP and DCHP in waste water, but below the LOQs of the method.

Background: Among patients with congenital hypothyroidism, 35% have dyshormonogenesis (DH) with thyroid gland in situ with or without goiter. The majority of DH cases are due to mutations in genes involved in thyroid hormone production as TG, TPO, SLC5A5/NIS, SLC26A4/PDS, IYD/DEHAL1, DUOX2, and DUOXA2, and are usually inherited on an autosomal recessive basis. Most previously reported cases of fetal hypothyroidism and goiter were related to TG or TPO mutations and recently DUOXA2. Patient: In a male patient with antenatal goiter treated with intraamniotic levothyroxine injections, whose long-term follow-up is described in detail, two novel NIS mutations were detected. Mutations of NIS were located in exon 1 (c.52G>A, p.G18R) and exon 13 (c.1546C>T, p.R516X), each mutation was inherited from parents, who are healthy carriers. The p.G18R mutation affecting the first transmembrane domain of the protein can be responsible for deficient iodide uptake. However, the second is a nonsense mutation leading probably to mRNA degradation. In addition, the patient has undergone a thyroidectomy and we have studied the thyroid tissue. The thyroid histology showed heterogeneity with large follicles, epithelial hyperplasia and many areas of fibrosis. Immunohistochemistry with NIS specific antibody showed NIS staining at the basolateral plasma membrane of the thyrocytes. Conclusions: We report the first case of fetal goitrous hypothyroidism due to two novel NIS mutations with access to thyroid tissue of the patient, specific histology studies and long-term follow-up. This case expands our knowledge and provides further insights on molecular causes of fetal goiter in humans.

Objectives. The aim of the paper is to analyze the process of acquisition of mental state verbs in Romani and in Bulgarian langauges simultaneously by bilingual Roma children. The mental state verbs help the children to understand the Fals Belief Tasks, which predict the Theory of Mind. The theory of mind from other side is important for understanding the intentions, desires, jokes, motivations of others and what are the factors influencing the development of theory of mind Research methods and techniques. Two Roma children from Bulgaria (1 boy and 1 girl) aged 1;0 – 3;0 years were audiorecorded longitudinally in their natural home environment. According to M. Taumoepeau and T. Ruffman (2006), the mental state verbs can be grouped in different categories, showing different states: mental states, physical states, emotions, perception and cognition. The acquired verbs are analyzed qualitatively and quantitatively. Results. The data shows that some mental state verbs are acquired in Romani and others in Bulgarian. The factors influencing the acquisition of part of the verbs in Romani and the other part in Bulgarian are analyzed. Mental state verbs are important for the cognitive development of the children. The results show that the the boy uses 100% Romani mental state verbs: very high number of verbs are related to (1) mental states, e.g.: mangav (want), dehav (love), arakhav (care about), džanav (know); (2) emotions: xavxoli (angry), khanile (feeling bad); (3) physical state, e.g.: dukhal (hurt), rovav (cry); (4) sense, such as: dikh (look). The girl uses 89.0% mental state verbs in Romani and 19.0% in Bulgarian language. The learned verbs by her are related to mental state from Romani: mangav (want), džanav (know), darav (be afraid) and from Bulgarian: obicham (love), znam (know), iskam (want). The other verbs from the field of emotions, physical state and sense are from Romani. Conclusions. The resreach although limited has shown that sentences with mental state verbs in a combination with a noun phrase in a simple sentence are acquired around the age of 1;6. The more complex sentences with mental state verb and complementizer phrase are acquired around the age of 2;6 years old.

Thyroid hormones (TH), namely 3,5,3’-triiodothyronine (T3) and its precursor thyroxine (T4), are key regulators of growth processes and development, and crucially control the energy metabolism. A proper availability of iodine within the thyroid is crucial for the synthesis of TH in order to maintain the homeostasis of circulating levels. The daily dietary iodine intake is not sufficient to sustain their synthesis and, in fact, most of the intra-thyroidal iodine is recycled through the activity of the Iodotyrosine Dehalogenase-1 (DEHAL-1) enzyme. Mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) precursors produced in excess during TH synthesis, are deiodinated by DEHAL-1, leading to the production of I- and Tyr that are recycled and reused within the thyroid. In the last decade, human mutations of DEHAL1 causing the impairment of its catalytic activity were reported. The clinical picture caused by these mutations recapitulates the phenotype of what is known as Iodotyrosine deiodinase deficiency (ITDD), characterized by hypothyroidism, goitre and, if not treated during childhood, by intellectual impairments. A hallmark of ITDD resides in the increase of urinary and plasmatic MIT and DIT levels. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS-MS) is a powerful technique characterized by high specificity and sensitivity. Even if clinical testing of TH is still performed using immunoassays, various HPLC-MS-MS methods to assay TH at low concentrations have been proposed. HPLC-MS-MS is now emerging as a powerful technique that complements traditional testing overcoming some of their limitations. Hitherto, only one HPLC-MS-MS method have been proposed in order to assay MIT and DIT levels in urine that has been used in the discovery of one of the most recent discovered human DEHAL1 mutations. The aim of my project was to develop a sensitive and robust HPLC-MS-MS method able to quantify MIT and DIT in urine and plasma, together with T3 and T4 in the latter case. The method was extensively validated and used to assay these molecules in urine and plasma collected from the novel Dehal1 knock-out mouse. Our method played a crucial role in the biochemical characterization of this first mammalian model of defective iodine recycling through DEHAL-1 deletion. We detected increased urinary and plasmatic levels of MIT and DIT in the knock-out mice and we demonstrated the presence of elevated concentrations of both molecules even at the first stage of life. The influence of iodine availability was tested, showing that mice were still euthyroid when levels of dietary iodine were sufficiently high. In the presence of scarce iodine availability, coupled to the impaired ability to recycle iodine through DEHAL-1, knock-out mice became hypothyroid. Our results demonstrated the importance of iodine availability in triggering hypothyroidism in the presence of ITDD. The importance of a powerful technique able to detect MIT and DIT was demonstrated assaying these molecules in human urine collected from a consanguineous family with a diagnosed DEHAL-1 deficiency. Our HPLC-MS-MS method was able to detect elevated urinary levels of MIT and DIT in the index patient that was clinically diagnosed with ITDD showing goitre and hypothyroidism. Remarkably, we detected a massive increase of both molecules in urine collected from one of the brothers that was healthy at the time of sample collection but that developed hypothyroidism and goitre several years later. In conclusion, our findings demonstrated the ability of our validated HPLC-MS-MS method to detect MIT, DIT together with T3 and T4 in urine and plasma samples. We showed the potential of MIT and DIT assay, especially in urine, for the early detection of hypothyroidism in DEHAL-1 deficiency. Considering the presence from the beginning of life, the detection of iodotyrosines could be potentially included in the human new-born screening for hypothyroidism.