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Proper CNS myelination depends on the timed availability of thyroid hormone (TH) that induces differentiation of oligodendrocyte precursor cells (OPCs) to mature, myelinating oligodendrocytes. Abnormal myelination is frequently observed in Allan-Herndon-Dudley syndrome caused by inactivating mutations in the TH transporter MCT8. Likewise, persistent hypomyelination is a key CNS feature of the Mct8/Oatp1c1 double knockout (Dko) mouse model, a well-established mouse model for human MCT8 deficiency that exhibits diminished TH transport across brain barriers and thus a TH deficient CNS. Here, we explored whether decreased myelin content is caused by an impairment in oligodendrocyte maturation. To that end, we studied OPC and oligodendrocyte populations in Dko mice versus wild-type and single TH transporter knockout animals at different developmental time points (at postnatal days P12, P30, and P120) using multi-marker immunostaining and confocal microscopy. Only in Dko mice we observed a reduction in cells expressing the oligodendroglia marker Olig2, encompassing all stages between OPCs and mature oligodendrocytes. Moreover, Dko mice exhibited at all analysed time points an increased portion of OPCs and a reduced number of mature oligodendrocytes both in white and grey matter regions indicating a differentiation blockage in the absence of Mct8/Oatp1c1. We also assessed cortical oligodendrocyte structural parameters by visualizing and counting the number of mature myelin sheaths formed per oligodendrocyte. Again, only Dko mice displayed a reduced number of myelin sheaths that in turn exhibited an increase in length indicating a compensatory response to the reduced number of mature oligodendrocytes. Altogether, our studies underscore an oligodendrocyte differentiation impairment and altered oligodendrocyte structural parameters in the global absence of Mct8 and Oatp1c1. Both mechanisms most likely do not only cause the abnormal myelination state but also contribute to compromised neuronal functionality in Mct8/Oatp1c1 deficient animals.

Macroscopic hematuria is the most common telltale clinical sign for muscle-infiltrating or non-muscle bladder tumors. Lower urinary tract disorders, pelvic pain or signs related to upper urinary tract obstruction may be associated. In our case, the reason for consultation is sciatica, progressing to functional impairment of the lower right limb without any urological sign.

Objective: Acanthamoeba keratitis cause severe corneal infection and lead to poor vision and blindness. This disease is caused by a unicellular amphizoic protozoon called Acanthamoeba spp. that present in different environments. This study aimed to represent the existence and genotyping of Acanthamoeba spp. in patients with keratitis and swimming pool water (SPW) in Tehran Province, Central Iran. Methods: In this descriptive study, 56 clinical samples were collected from patients with keratitis and 30 water samples were collected from different swimming pools in Tehran Province. All samples were examined based on the morphological and molecular techniques. The genotypes were determined by sequencing the partial of 18S rRNA gene. Results: Of 56 clinical (corneal) and 30 environmental (SPW) samples, 30.3% and 40.0% were positive for Acanthamoeba spp., respectively. According to sequencing analysis, 94.1% of amoebic keratitis isolates were belonged to T4 genotype and only one (5.8%) isolate was belonged to T11 genotype. All genotypes were detected from SPW samples were identified as T4 genotype. Conclusion: According to our results, use of contact lens and swimming in pool poses the major risk factor for amoebic keratitis in the studied area (Tehran). Moreover, T4 genotype was the predominant genotype of human keratitis and swimming pool samples there. Consequently, essential and practical measures are urgently needed to prevent subjects against this ocular seriously disease.

Bis (2-ethylhexyl) tetrabromophthalate (TBPH) is a new type of brominated flame retardant. Some studies suggest that TBPH exposure may be associated with thyroid damage. However, there is a paucity of research on the authentic exposure-related effects and molecular mechanisms in animals or cells. In this study, we used male Sprague-Dawley (SD) rats and the Nthy ori3-1 cell line (the human thyroid follicular epithelial cell) to explore the potential effects of TBPH (5, 50, 500 mg/kg and 1, 10, 100 nM) on the thyroid. The genes and their proteins of cytokines and thyroid-specific proteins, thyroglobulin (TG), thyroid peroxidase (TPO), and sodium iodide cotransporter (NIS) were examined to investigate the possible mechanisms. At the end of the experiment, it was found that 50 and 500 mg/kg TBPH could increase the levels of total thyroxine (TT4) and free thyroxine (FT4) significantly. The messenger RNAs (mRNAs) of Tg, Tpo, Interleukin-6 (Il6), and Interleukin-10 (Il10) in the thyroid tissues from the rats treated with 500 mg/kg were enhanced clearly. Meanwhile, the mRNAs of TG, TPO, IL6, and IL10 were elevated in Nthy ori3-1 cells treated with 100 nM TBPH as well. The mRNAs of TG and TPO were elevated after the knockdown of IL6. To our surprise, after the knockdown of IL10 or the treatment of anti-IL-10-receptor (anti-IL-10-R) antibody, the mRNAs of TG and TPO were significantly reduced, and the effects of TBPH were diminished. In conclusion, our results suggested that the IL-10-IL-10R-TG/TPO-T4 axis is one important target of TBPH in the thyroid., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Phenotypic screening is gaining attention as a powerful method for identifying compounds that regulate cellular phenotypes of interest through novel mechanisms of action. Recently, a new modality of compounds, called molecular glues, which can induce the degradation of target proteins by forming ternary complexes of E3 ligases, has emerged from phenotypic screening. In this study, using global proteomic analysis, we identified a novel Cyclin K degrader, T4, which was previously discovered through phenotypic screening for alternative polyadenylation regulation. Our detailed mechanistic analysis revealed that T4 induced Cyclin K degradation, leading to the regulation of alternative polyadenylation. Additionally, we generated a more potent Cyclin K degrader, TR-213, through a structure-activity relationship study of T4. T4 and TR-213 are structurally distinct from other Cyclin K degraders and can be used as novel chemical tools to further analyze the degradation of Cyclin K and the regulation of alternative polyadenylation., Competing Interests: Declaration of competing interest In accordance with the journal's policy regarding conflicts of interest, all the authors are employees of Takeda Pharmaceutical Co., Ltd., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Thyroid hormones (TH) are known to play an important role in the growth and development of vertebrates. In fish species, TH regulates the larval-juvenile metamorphosis, and is crucial for development during early life stages. Monitoring the variations in TH levels at different life stages can provide insights into the regulation of metamorphosis and fish development. In this study, we developed an extremely sensitive method for the quantification of thyroxine (T4), triiodothyronine (T3), and reverse-triiodothyronine (rT3), in lake sturgeon (Acipenser fulvescens) tissues from eggs, free embryos, larvae, and juveniles. The target compounds were extracted by an enzymatic digestion method, followed by protein precipitation. Further cleanup was performed by liquid-liquid extraction (LLE) and solid phase extraction (SPE) using SampliQ OPT cartridges. The liquid-chromatography tandem mass spectrometry (LC-MS/MS) method used to quantify TH compounds showed remarkably high sensitivity with the limit of detection (LOD) and the limit of quantification (LOQ) ranging from < 1 pg/mL to 10 pg/mL and linearity in the range of 10-50,000 pg/mL. This method was validated for tissue samples across several early developmental stages and was checked for intra- and inter-day accuracy (78.3-111.2 %) and precision (0.1-4.9 %), matrix effect (75.4-134.1 %), and recovery (41.2-69.0 %). The method was successfully applied for the quantification and comparison of T4, T3 and rT3 in hatchery raised lake sturgeon samples collected at unique time points (i.e., days post fertilization dpf) including fertilized eggs (11 dpf), free embryos (14 dpf), larvae (22 dpf), juveniles (40 dpf) and older juveniles (74 dpf). With modifications, this method could be applied to other species important for agriculture or conservation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Laparoscopic (lap) colectomies for advanced colorectal cancer (CRC) often require resection of other organs. We systematically reviewed currently available literature on lap multi-visceral resection for CRC, with regard to short- and long-term oncological outcomes, and compared them with open procedures. We performed a systematic literature search in MEDLINE, EMBASE, Google Scholar and PubMed from inception to November 30, 2020. The aim of this study was to synthesize short-term and oncological outcomes associated with laparoscopic versus open surgery. Pooled proportions and risk ratios (RRs) were calculated using an inverse variance method. We included six observational cohort studies published between 2012 and 2020 (lap procedures: n = 262; open procedures: n = 273). Collectively, they indicated that postoperative complications were significantly more common after open surgeries than lap surgeries (RR: 0.53; 95% confidence interval [CI]: 0.39-0.72; P < 0.00001), but the two approaches did not significantly differ in positive resection margins (RR: 0.75; 95% CI: 0.38-1.50; P = 0.42), local recurrence (RR: 0.66; 95% CI: 0.28-1.62; P = 0.37), or (based on two evaluable studies) 5-year OS (RR: 0.70; 95% CI: 0.46-1.04; P = 0.08) or 5-year DFS (RR: 0.86; 95% CI: 0.67-1.11) for T4b disease. In conclusion, laparoscopic and open multi-visceral resections for advanced CRC have comparable oncologic outcomes. Although a randomized study would be ideal for further research, no such studies are currently available., Competing Interests: Declaration of competing interest Drs Y Ishiyama, Y Tachimori, I Mochizuki, Y Tomozawa, S Ito, M Oneyama, M Amiki, Y Hara, K Narita, M Goto, K Sekikawa, and Y Hirano have no conflicts of interest or financial ties to disclose., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Minimally invasive surgery (MIS) is favored for T1-T3 colon cancer resection due to improved short and long-term outcomes. Recommendations regarding T4 cancers remain controversial due to a paucity of clinical trials or large datasets assessing outcomes. We aim to compare outcomes for pT4 colon cancer patients treated with MIS or open surgery (OS) in the National Cancer Database (NCDB). We analyzed adults having MIS or OS for stage II or III pT4 colon cancers between 2010 and 2014 using propensity-score matching, Cox and logistic regression modeling. Of 21 998 T4 patients, 7532 (34.2%) underwent MIS, 14 466 (65.8%) OS and 22.3% were MIS converted to OS. After propensity score matching, 5624 patients in each cohort were included. MIS was associated with improved postoperative mortality (3.4 vs. 7.2%, p > .001), surgical margins, optimal lymph node harvest, adjuvant chemotherapy use and 5-year survival (46% vs. 41%, P < .001). MIS was associated with improved short and long term outcomes for T4 colon cancers compared to OS on multivariate analysis. Based on these findings, well selected pT4 colon cancers can be considered appropriate for MIS however, prospective clinical trials are needed to better define the role of MIS in T4b colon cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The reported associations for several per- and polyfluoroalkyl substance (PFAS) with thyroid hormones are inconsistent in epidemiological studies. The purpose of the current study was to investigate the possible association of thyroid hormones in relation to serum levels of perfluorohexane sulfonate, perfluorooctane sulfonate and perfluorooctanoic acid, in a Swedish general population, highly exposed through contaminated drinking water, and if the associations with PFAS remained in a comparison to a reference group based only on residency in areas with contrasting PFAS levels., Method: 3297 participants from Ronneby, a municipality with drinking water highly contaminated by PFAS (exposed group), and a reference group (N = 226) from a nearby municipality with non-contaminated drinking water supply were included. Regression analysis was used to investigate the associations between PFAS exposure, assessed as exposure groups (Ronneby and reference groups) and measured serum PFAS levels, and thyroid hormone levels, with adjustments for age, sex and BMI., Result: No cross-sectional associations were found between PFAS and thyroid hormones in adults and seniors except for a positive association between PFAS and fT4 in males over 50. Higher thyroid hormone levels were found in the preteen children from Ronneby compared to the reference group. In contrast, within Ronneby, there was weak evidence of associations between increased PFAS levels and decreased fT3 in preteen boys, and decreased TSH in teenage males. No such pattern was found in preteen and teenage girls., Conclusion: The present study found no consistent evidence to support association of PFAS with thyroid hormones., (Copyright © 2020 Elsevier Inc. All rights reserved.)

During the last years there has been a growing interest in the development of methods for phage detection and quantification in environmental, public health and industrial sectors. Good methods of phage monitoring contribute to progress in phage therapies, biocontrol and food safety studies. They have also been used to indicate the possible presence of microbiological hazards in drinking and recreational waters, and are an essential tool to prevent failure of microbe-based industrial bioreactors. Many of the sophisticated methods that have emerged to cover these needs are strongly hampered by the presence of turbidity in the samples, that results in decreased sensitivity. To avoid this, time consuming pretreatment steps must often be included that increase the overall complexity of the assays and the time required to perform them. With this in mind, we have explored an alternative method that fulfills the criteria of being simple, rapid and inexpensive and can be used to perform analysis in turbid media without any pretreatment steps. In this paper we develop a method that monitors lysis of an indicator culture when exposed to samples containing the target phage. The method is based on the properties of resazurin, a redox dye that becomes fluorescent when reduced by an active microbial culture. We analyzed the fluorescence kinetics of non-turbid phage-infected bacterial cultures as a function of both, phage abundance and initial cell concentration. For this purpose, different phage/host combinations were used and then, the addition of resazurin at different times (0, 30 and 60 min) was carefully evaluated for each phage/host combination, thus providing data for 168 combinations in total. Next, selected phage/host combinations were tested over 4 different turbidity models: 0, 1000, 2000 Nephelometric Turbidity Units (NTU) as well as in milk. The data obtained provided information about the duration of the assay and sensitivity thresholds in matrices with different turbidity grades. The results obtained indicate that the method can detect as few as 10 phage particles per assay volume within 3.5 h. If sensitivity is not an issue and the threshold of detection is increased to 10 7 phages the assay is considerably shortened, providing reliable results in only 40 min. Overall, the detection approach proposed in this work provides a simple, rapid and inexpensive solution that compares favorably, in terms of performance, with other high-end methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Thyroid hormones (THs; T3 and T4) play a role in development of cardiovascular, reproductive, immune and nervous systems. Thus, interpretation of TH changes from rodent studies (during pregnancy, in fetuses, neonates, and adults) is critical in hazard characterization and risk assessment. A roundtable session at the 2017 Society of Toxicology (SOT) meeting brought together academic, industry and government scientists to share knowledge and different perspectives on technical and data interpretation issues. Data from a limited group of laboratories were compiled for technical discussions on TH measurements, including good practices for reliable serum TH data. Inter-laboratory historical control data, derived from immunoassays or mass spectrometry methods, revealed: 1) assay sensitivities vary within and across methodologies; 2) TH variability is similar across animal ages; 3) laboratories generally achieve sufficiently sensitive TH quantitation levels, although issues remain for lower levels of serum TH and TSH in fetuses and postnatal day 4 pups; thus, assay sensitivity is critical at these life stages. Best practices require detailed validation of rat serum TH measurements across ages to establish assay sensitivity and precision, and identify potential matrix effects. Finally, issues related to data interpretation for biological understanding and risk assessment were discussed, but their resolution remains elusive., (Copyright © 2019. Published by Elsevier Inc.)

A UPLC-MS/MS method was developed to provide a reproducible, sensitive and quantitative assay to determine thyroid hormones in sea lamprey tissues and plasma. l-Thyroxine (T4) and its two triiodo-thyronine isomers have been simultaneously quantified and validated for plasma, gill, liver, and kidney matrices. Multiple sample preparation techniques were investigated to achieve optimal sample matrix digestion and clean-up. Enzymatic digestion followed by protein precipitation was selected to process the samples. The developed method exhibited excellent linearity for all analytes with regression coefficients higher than 0.99 for concentrations ranged from 10 to 50,000pg/mL. The limit of detection (LOD) was under 1pg/mL while the limit of quantification (LOQ) was estimated as 10pg/mL. This method was validated according to the FDA guidance and applied to determine thyroid hormone levels in plasma, gill and kidney of sea lamprey exposed to a sex pheromone. With appropriate implementation and further validation, this method could be applied to tissues in other species including humans., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To study the natural history, prognosticators, and outcomes in patients with renal cell carcinoma (RCC) with extension of tumor beyond Gerota׳s fascia or invading contiguously into the adrenal gland (pT4) or both., Patients and Methods: From 1992 to 2012, we identified 61 patients who underwent radical nephrectomy and were found to have pT4 disease. Clinicopathologic variables were queried using univariate analysis to identify relevant prognostic variables. Cox proportional hazards model was used for multivariate analysis of predictors of cancer-specific survival. Survival plots were estimated using Kaplan-Meier method and survival analysis using log-rank test., Results: Median age was 56 years (interquartile range: 49-64) and 49 (81.7%) patients had Eastern Cooperative Oncology Group Performance Status 0 or 1. At diagnosis, 22 (36.1%) patients showed nonmetastatic and 39 (63.9%) patients showed metastatic RCC. Overall, 49 (80.3%) patients had clear cell RCC, 24 (39.3%) patients had sarcomatoid features, and 39 (69.6%) patients had Fuhrman grade 3 to 4. There were 26 (42.6%) patients with pN0, 16 (26.2%) patients with pN1, and 19 (31.1%) patients with pNx. Median cancer-specific survival was 37 months for patients with nonmetastatic and 8 months for patients with metastatic RCC. On multivariate analysis, preoperative lactate dehydrogenase and alkaline phosphatase, M stage, pN stage, and sarcomatoid dedifferentiation were significantly associated with survival., Conclusions: Survival in patients with pT4 remains poor. The pT4 disease is associated with a locally and regionally invasive biology that requires specific attention and warrants careful study. Understanding the drivers of this unique phenotype would generate therapeutic interventions that can change the behavior of these uniquely aggressive tumors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: Right ventricle (RV) dysfunction post-myocardial infarction (MI) was associated with a worsened prognosis. In this scenario, reactive oxygen species (ROS) are related with the progression from MI to heart failure. Previous work showed that thyroid hormones (TH) are cardioprotective after MI., Aims: This study aims to investigate the effect of T3 and T4 administration on oxidative stress and angiogenesis parameters in the RV after MI., Main Methods: Wistar rats were allocated into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT), and infarcted+TH (AMIT). The treated groups received T3 (2 μg/100g/day) and T4 (8 μg/100g/day) by gavage for 26 days. After this, echocardiographic analysis was performed and the RV was collected to western blot and biochemical analysis., Key Findings: Infarcted treated rats showed RV hypertrophy compared with AMI and SHAMT. Hydrogen peroxide levels were decrease and SOD activity and expression were increased in the infarcted treated rats. Besides that, the hormonal administration increased eNOS expression and prevented the reduction of VEGF levels in AMIT rats., Significance: In conclusion, TH seems to improve oxidative stress parameters, to promote physiological hypertrophy and to increase the expression of proteins involved with angiogenesis in the right heart., (Copyright © 2016 Elsevier Inc. All rights reserved.)

T4 tumors that invade the heart, great vessels, or esophagus comprise a heterogenous group of locally invasive lung cancers. Prognosis depends on nodal status; this relationship has been consistently demonstrated in many of the small series of extended resection. Current National Comprehensive Cancer Network guidelines do not recommend surgery for T4 extension with N2-3 disease (stage IIIB). However, biopsy-proven T4 N0-1 (stage IIIA) may be operable. Localized tumors with invasion of the aorta, pulmonary artery, left atrium, or esophagus represent a small subset of T4 disease. Acquiring sufficient randomized data to provide statistical proof of a survival advantage for patients undergoing extended resections for these neoplasms will likely never be possible.Therefore, we are left to critically analyze current documented experience to make clinical decisions on a case-by-case basis.It is clear that the operative morbidity and mortality of extended resections for locally advanced T4 tumors have significantly improved over time,yet the risks are still high. The indications for such procedures and the anticipated outcomes should be clearly weighed in terms of potential perioperative complications and expertise of the surgical team. Patients with T4 N0-1 have the best prognosis and with complete resection may have the potential for cure. The use of induction therapy and surgery for advanced T4 tumors may improve survival. Current data suggest that for tumors that invade the aorta, pulmonary artery,left atrium, or esophagus, resection should be considered in relation to multidisciplinary care.For properly selected patients receiving treatment at high volume, experienced centers, extended resections may be warranted., (Published by Elsevier Inc.)

European starlings (Sturnus vulgaris) are a valuable model species for the assessment of concentrations and effects of environmental contaminants in terrestrial birds. Polybrominated diphenyl ethers (PBDEs) are found in birds throughout the world, but relatively little is known of their concentrations or effects in free-living terrestrial passerines. We used a nest box population of European starlings to 1) measure the variation in egg concentrations of persistent organohalogen contaminants at an agricultural site, and 2) assess whether individual variation in PBDE concentrations in eggs was related to reproductive parameters, as well as maternal or nestling characteristics including body condition, thyroid hormones, oxidative stress, and hematocrit. As PBDEs were the main contaminant class of interest, we only assessed a subset of eggs for other organohalogen contaminants to establish background concentrations. Exposure to organohalogen contaminants was extremely variable over this relatively small study area. Geometric mean wet weight concentrations (range in brackets) of the major contaminants were 36.5 (12-174) ng/g ΣDDT (n=6 eggs) and 10.9 (2-307) ng/g ΣPBDEs (n=14). ΣPCBs at 3.58 (1.5-6.4) ng/g (n=6) were lower and less variable. There were low levels of other organochlorine (OC) pesticides such as dieldrin (2.02 ng/g), chlordanes (1.11 ng/g) and chlorobenzenes (0.23 ng/g). The only form of DDT detected was p,p'-DDE. The congener profiles of PBDEs and PCBs reflect those of industrial mixtures (i.e. DE-71, Aroclors 1254, 1260 and 1262). For all of the contaminant classes, concentrations detected in eggs at our study site were below levels previously reported to cause effects. Due to small sample sizes, we did not assess the relationship between ΣPCBs or ΣOCs and adult or chick condition. We observed no correlative relationships between individual variation in PBDE concentrations in starling eggs and reproductive success, maternal condition, or nestling condition in the corresponding nests., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Thyroperoxidase (TPO), the enzyme that catalyzes the synthesis of thyroid hormone, is a known target for thyroid-disrupting chemicals. In vivo toxicological evidence supporting TPO-inhibition as one molecular-initiating event that leads to thyroid disruption is derived largely from rat models; however, a significant fraction of research on the inhibition of TPO by xenobiotics has been conducted using porcine TPO. The current work tested the hypothesis that porcine and rat thyroid microsomes exposed to TPO-inhibiting chemicals would demonstrate different responses in a guaiacol oxidation assay. A primary objective of this work is to establish the degree of concordance between rat and porcine TPO inhibition data. Microsomes were isolated from both rat and pig thyroid glands, and the guaiacol oxidation assay was performed for a training set of 12 chemicals, including previously reported TPO inhibitors, thyroid-disrupting chemicals thought to perturb other targets, and several previously untested chemicals, to determine the relative TPO inhibition responses across species. Concentration-response curves were derived for methimazole (MMI), dibutylphthalate (DBP), diethylhexylphthalate (DEHP), diethylphthalate (DEP), 3,5-dimethylpyrazole-1-methanol (DPM), iopanoic acid (IOA), 2-mercaptobenzothiazole (MBT), sodium perchlorate (PERC), p-nonylphenol (PNP), 4-propoxyphenol (4POP), 6-propylthiouracil (PTU), and triclosan (TCS). MMI, PTU, MBT, DPM, 4POP, and at extremely high concentrations, PERC, inhibited TPO activity. Results demonstrated a strong qualitative concordance of response between the two species. All chemicals that inhibited TPO in porcine microsomes also inhibited TPO in rat microsomes. Hill model-derived IC50 values revealed approximate 1.5- to 50-fold differences in relative potency to MMI between species for positive chemicals. DPM, MBT, 4POP, and PTU exhibited greater relative potency to MMI using rat TPO versus porcine TPO, but rank order potency for inhibition was similar for the other test chemicals, with: PTU>MBT>DPM>4POP>PERC for rat TPO and MBT>PTU>DPM>4POP>PERC for porcine TPO. These data support the extrapolation of porcine TPO data to potential thyroid-disrupting activity in rodent models to evaluate TPO-inhibiting chemicals., (Published by Elsevier Ireland Ltd.)

Timely diagnosis and treatment of thyroid dysfunction is compelling given the prevalence and severity of the disease. It requires reliance on adequate laboratory testing of serum TSH as a hallmark in combination with free thyroxine/triiodothyronine. Free hormone methods have to accommodate variations in the concentration and binding capacity of binding proteins. This is a challenge because none of the methodologies developed so far measures the actual unbound hormone in serum. The indirect methods provide an approximation while the direct ones estimate the free hormone concentration either in the presence of the protein-bound counterpart, or after physical separation of the free from bound fraction. The ongoing controversy on the validity and lack of comparability of methodologies points to their imperfectness to reflect real in-vivo free hormone concentrations. Therefore, laboratories and clinicians should know the window of validity and limitations of their methods. The recently developed reference measurement system is a key advance towards improved standardization and clinical validity of free thyroid hormone measurements., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Endocrine-disrupting chemicals currently represent one of the major concerns and this study was aimed to investigate the effects of different doses of cadmium, widespread toxic metal, on the levels of thyroid hormones and to calculate Benchmark doses for these effects. Furthermore, the effects of co-exposure to cadmium and polychlorinated biphenyls on thyroid function were investigated. Six orally-treated groups of rats were receiving 0.3, 0.6, 1.25, 2.5, 5 and 10mgCd/kgb.w./day, five groups were orally treated with 0.5, 1, 2, 4 and 8mgPCBs/kgb.w./day, while nine groups of rats were orally-treated with different dose combinations of Cd and PCBs (0.6, 1.25 and 2.5mgCd/kgb.w. and 2, 4 and 8mgPCBs/kgb.w./day), during 28 days. Thyroid hormones were adversely affected by cadmium, with most prominent effect observed on triiodothyroxine levels indicating Cd interference with thyroid function at extrathyroidal level. Calculated Benchmark doses for Cd effects on thyroid hormones indicate triiodothyroxine as the most sensitive one that can be used as a basis for risk assessment. This study also implicates possible synergistic effects of Cd and PCBs on thyroid function as a consequence of their interference at different levels of thyroid homeostasis., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Amiodarone-induced thyrotoxicosis (AIT) is a recognized complication of amiodarone treatment with limited management options. Its predisposing factors are incompletely defined yet a higher prevalence was reported in adults with congenital heart disease (CHD). Therefore we sought to determine the incidence and risk factors for AIT in adults with CHD., Methods: At a tertiary care center we followed a historical cohort of amiodarone-treated CHD patients for the period 1987-2009. Follow-up concluded at AIT diagnosis or with last thyroid assessment on amiodarone. Cumulative incidence of AIT was calculated. AIT association with nutritional status was hypothesized a priori., Results: AIT developed in 23/169 patients or 13.6%. The AIT incidence peaked in the 3rd year at 7.7%. AIT patients had a lower body mass index (BMI) at AMIO initiation compared with the rest of the cohort (mean ± standard deviation: 21.9 ± 2.9 vs. 25.1 ± 5.0; p<0.001). Patients with BMI<21 were more likely to develop thyrotoxicosis (RR=6.1) compared to those with BMI>25 (p<0.001). Presence of goiter was strongly associated with AIT (RR 3.6, p=0.002). Affected patients had a trend for higher cyanotic heart disease prevalence (34.8% vs. 17.8%, p=0.059). On multivariate analysis body mass index and goiter remained independent predictors of outcome., Conclusions: BMI<21 at initiation of amiodarone therapy and presence of goiter are strong predictors of AIT in this population. Its incidence is time dependent. These predictors can be used clinically in assessing overall impact of amiodarone therapy in congenital heart disease patients., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)