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Disruption of the thyroid hormone system by synthetic chemicals is gaining attention owing to its potential negative effects on organisms. In this study, the effects of the dio-inhibitor iopanoic acid (IOP) on the levels of thyroid hormone and related gene expression, swim bladder inflation, and swimming performance were investigated in Japanese medaka. Iopanoic acid exposure suppressed thyroid-stimulating hormone β (tshβ), tshβ -like, iodotyronin deiodinase 1 (dio1), and dio2 expression, and increased T4 and T3 levels. In addition, IOP exposure inhibited swim bladder inflation, reducing swimming performance. Although adverse outcome pathways of thyroid hormone disruption have been developed using zebrafish, no adverse outcome pathways have been developed using Japanese medaka. This study confirmed that IOP inhibits dio expression (a molecular initiating event), affects T3 and T4 levels (a key event), and reduces swim bladder inflation (a key event) and swimming performance (an adverse outcome) in Japanese medaka. [Display omitted] • IOP disrupts thyroid hormone activity in Japanese medaka. • IOP suppresses dio expression. • IOP reduces swim bladder inflation and swimming performance. • Adverse outcome pathway of IOP is established in Japanese medaka. [ABSTRACT FROM AUTHOR]

• Lungtumors positioned adjacent to the central airways can be visualized by EBUS. • EBUS imaging can assess the presence or absence of mediastinal/vascular tumor invasion. • EBUS provides important additional staging information complementary to CT findings. • T4 assessment by EBUS cab be considered following an nodal examination. In lung cancer patients, accurate assessment of mediastinal and vascular tumor invasion (stage T4) is crucial for optimal treatment allocation and to prevent unnecessary thoracotomies. We assessed the diagnostic accuracy of linear endobronchial ultrasound (EBUS) for T4-status in patients with centrally located lung cancer. This is a retrospective study among consecutive patients who underwent EBUS for diagnosis and staging of lung cancer in four hospitals in The Netherlands (Amsterdam, Leiden), Italy (Bologna) and Poland (Zakopane) between 04–2012 and 04−2019. Patients were included if the primary tumor was detected by EBUS and subsequent surgical-pathological staging was performed, which served as the reference standard. T4-status was extracted from EBUS and pathology reports. Chest CT's were re-reviewed for T4-status. 104 patients with lung cancer in whom EBUS detected the primary tumour, and who underwent subsequent surgical-pathological staging were included. 36 patients (35 %) had T4-status, based on vascular (n = 17), mediastinal (n = 15), both vascular and mediastinal (n = 3), or oesophageal invasion (n = 1). For EBUS, sensitivity, specificity, PPV and NPV for T4-status were (n = 104): 63.9 % (95 %CI 46.2–79.2 %), 92.6 % (83.7–97.6 %), 82.1 % (65.6–91.7 %), and 82.9 % (75.7–88.2 %), respectively. For chest CT (n = 72): 61.5 % (95 %CI 40.6–79.8 %), 37.0 % (23.2–52.5 %), 35.6 % (27.5–44.6 %), and 63.0 % (47.9–75.9 %), respectively. When combining CT and EBUS with concordant T4 status (n = 33): 90.9 % (95 %CI 58.7–99.8 %), 77.3 % (54.6–92.20 %), 66.7 % (47.5–81.6 %), and 94.4 % (721−99.1%), respectively. Both EBUS and CT alone are inaccurate for assessing T4-status as standalone test. However, combining a negative EBUS with a negative CT may rule out T4-status with high certainty. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a systemic inflammatory response syndrome with high mortality. There is an upward trend in sepsis prevalence and mortality worldwide. Early and accurate prediction of outcome in sepsis is important. There remains a great need to improve a reliable prognostic model for sepsis patients with widely available variables. The aim of this study was to explore the correlation between serum thyroid hormone levels and prognosis in sepsis patients.Methods: Septic patients were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Factors that were found to contribute to the outcome in the uni-variate analysis at P value <0.1 were included in the multivariate. Multivariate analysis was performed by binary logistic regression analysis, which allows adjust for confounding factors. We combined an assessment of thyroid hormone and some variables together, which improve the accurate prediction of outcome. The accuracy of the test was assessed measuring the area under the ROC curve (AUROC).Results: A total of 929 eligible septic patients were included in the data analysis. Seventy hundred and three patients had a good functional outcome, whereas 226 patients had a bad functional outcome. Thyroxin (T4) level was significantly decreased in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome (P < 0.01). Binary logistic regression analyses revealed that lower thyroxin concentrations on admission were associated with a risk for poor outcomes (OR 0.556, 95% CI 0.41-0.75; P < 0.01). In addition, in ROC curve analysis, the combined model AUROC was 0.82 for ICU survival, which was significantly higher than the AUROCs of original fT4 (0.65 and 0.65), T4 (0.71 and 0.71) and SAPSII (0.70 and 0.72) (all P < 0.05).Conclusions: Low serum thyroxin levels can be a predictive marker of short-term outcome after sepsis. A combined model (fT4, T4 and SAPSII score) can add significant additional predictive information to the clinical score of the SAPSII. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• This is the first case series that study directly the effect of Thyroxin medication on dental implants. • The presented data would support or defet the data in literature. • More than one parameter for implant's success were used for all the presented cases. Hypothyroidism reduces the recruitment, maturation, and activity of bone cells, decreasing bone resorption and formation. Several investigations have reported that T4 replacement therapy is associated with a significant decrease in bone mineral density in various skeletal parts, while others have failed to corroborate these results. The present study describes both a literature review and our own experience with dental implants in patients with hypothyroidism undergoing T4 replacement therapy. The study included two parts: a literature review and case series. The literature review included 12 articles documenting the success rate of osseointegrated dental implants in patients with hypothyroidism. The clinical cases were chosen from King Saud University Dental College, Riyadh. The patients' identity was only available to the main researcher. The inclusion criteria for the clinical cases were: T4-treated hypothyroidism, age 20–60 years, and use of dental implants with a follow-up period of 6–12 months after loading. The exclusion criteria were: any other medical condition alongside hypothyroidism, syndromic hypothyroidism, pregnancy, current smoking, bruxism, and hypothyroidism caused by surgical excision combined with radiotherapy. The following parameters were assessed: insertion torque (IT), crestal bone height (CBH), mesial bone width (MBW), and distal bone width (DBW) at different time points, probing depth, and signs of infection. Seventeen dental implants placed in patients with T4-treated hypothyroidism showed median IT success (42.4 N⋅cm; range: 35–45 N⋅cm). The median crestal bone loss was measured at 6–12 months after loading was 0.6 mm (range: 0.5–0.7. mm). Conversely, the median bone loss differences in MBW and DBW at 6–12 months after loading were 0.3 mm and 0.2 mm, respectively. After a 1-year follow-up, patients with T4-treated hypothyroidism who had received dental implants fulfilled the criteria for successful implants. [ABSTRACT FROM AUTHOR]

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 107 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. Image 1 • Detection of bacteriophages in turbid samples and in milk. • The method does not require pre-treatment of the samples. • Simple, rapid and sensitive. • Suitable for miniaturization, automation and high-throughput analysis. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Bis (2-ethylhexyl) tetrabromophthalate (TBPH) increased the level of T4 in male rats. • TBPH changed the expressions of thyroglobulin (TG) and thyroid peroxidase (TPO). • IL-10 might contribute to TG and TPO upregulation. [ABSTRACT FROM AUTHOR]

• There is an imperative need to align interpretation of thyroid hormone results. • We evaluated 124 regulatory repro screening studies including thyroid hormone data. • 38% of the studies showed a significant finding for T4 in treated animals. • This is probably due to disturbances of normal homeostasis causing high variation. • So, it is important to consider the historical control range in data evaluation. Recently several OECD test guidelines were updated to include thyroid hormone measurements for assessing endocrine disruptor potency, which led to an imperative need to align interpretation of these results by the different stakeholders. We therefore evaluated 124 repro screening studies, which showed in 38% of the studies a statistical significant finding for T4 in at least one treatment group, probably due to disturbances of normal homeostasis causing high variation. Consequently, for a thorough evaluation it is extremely important to take the historical control range into account. In conclusion, the current testing approach is not providing specific information needed to assess endocrine disruption, as too often a statistical significant finding is noted and as down-stream adverse effects are not evaluated. Therefore, major modifications are urgently needed. Instead of extending the in vivo experiments, it should be investigated if in vitro assessments will provide more relevant information on human endocrine disruptor potential. [ABSTRACT FROM AUTHOR]

Abstract Freshwater turtles are long-lived sedentary organisms used as biological sentinels to assess anthropogenic perturbations in freshwater-ecosystems; notably because pollutants tend to accumulate in their tissues. Pollution has detrimental effects in sea turtles, but studies in freshwater turtles have provided contrasted results: several species have been impacted by habitat perturbation and pollution while others not. It is important to explore this issue since freshwater turtles are threatened worldwide. We compared two populations of the stripe necked terrapin (Mauremys leprosa) in a relatively pristine area (piedmont of the Atlas mountain) versus an extremely degraded-polluted area (sewers of a large city) in Morocco. All morphological and physiological proxies showed that turtles were able to cope remarkably well with highly degraded-polluted habitat. Population density, body size, and body condition were higher in the sewers, likely due to permanent water and food availability associated with human wastes. Stress markers (e.g. glucocorticoids) provided complex results likely reflecting the capacity of turtles to respond to various stressors. Reproductive parameters (testosterone level, indices of vitellogenesis) were lower in the relatively pristine area. The deceptive overall image provided by these analyses may hide the disastrous human impact on rivers. Indeed, Mauremys leprosa is the only aquatic vertebrate able to survive in the sewers, and thus, might nonetheless be a pertinent indicator of water quality, providing that the complexity of eco-physiological responses is considered. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Introduction: The oncologic benefit of multivisceral en bloc resections for T4 gastroesophageal tumors has been questioned, given the increased morbidity associated. We thus sought to investigate the surgical and oncologic outcomes of curative-intent en bloc multivisceral resections for T4 gastroesophageal carcinomas.Methods: Between 2005 and 2016, 35 of the 525 patients who had gastric or EGJ carcinomas underwent curative-intent multivisceral resections for direct invasion or adhesion to adjacent organs.Results: Postoperative complications occurred in 16(46%), 10 of which were Clavien-Dindo ≥ 3 (29%). Ninety-day mortality was 3%. The R0 resection rate was 94% (33). Direct organ invasion (pT4b) was confirmed on pathological analysis in 14 (40%) and did not affect survival. The majority (28, 80%) had lymph node involvement with a high nodal disease burden and was associated with decreased survival. Overall 5-year survival rate was 34%, and the vast majority of recurrences were distant/peritoneal (81%). On multivariate analysis, positive lymph nodes (H.R. 21.2; 95%CI 2.34-192) and R1 resection (H.R. 5.6; 95%CI 1.02-30.9) were predictors of survival.Conclusion: Multivisceral resections for T4 gastric and GEJ adenocarcinomas, in combination with effective systemic therapy, result in prolonged long-term survival with acceptable morbidity. Complete resection to negative margins should remain a mainstay of curative-intent treatment in carefully selected patients. [ABSTRACT FROM AUTHOR]

Highlights • Recent update of OECD guidelines with thyroid hormone analyses. • Urgency for optimization and harmonization of analyses and their interpretation. • Overview of current issues and activities, and recommendations for moving forward. Abstract In recent years several OECD test guidelines have been updated and some will be updated shortly with the requirement to measure thyroid hormone levels in the blood of mammalian laboratory species. There is, however, an imperative need for clarification and guidance regarding the collection, assessment, and interpretation of thyroid hormone data for regulatory toxicology and risk assessment. Clarification and guidance is needed for 1) timing and methods of blood collection, 2) standardization and validation of the analytical methods, 3) triggers for additional measurements, 4) the need for T4 measurements in postnatal day (PND) 4 pups, and 5) the interpretation of changes in thyroid hormone levels regarding adversity. Discussions on these topics have already been initiated, and involve expert scientists from a number of international multisector organizations. This paper provides an overview of existing issues, current activities and recommendations for moving forward. [ABSTRACT FROM AUTHOR]

Myocardial infarction leads to oxidative stress and promotes activation of the TLR4/NF-κβ proinflammatory pathway. Thyroid hormones (TH) are known to be cardioprotective after infarction. However, there are no studies evaluating whether TH could modulate this pathway in the heart. This study aimed to verify the effect of thyroid hormones on the TLR4/NF-κβ pathway after myocardial infarction. Male Wistar rats were allocated into the following groups: Sham-operated (SHAM), sham-operated + TH (SHAMT), infarcted (AMI) and infarcted + TH (AMIT). The treated rats received T4 and T3 (8 and 2 μg 100 g −1 day −1 ) for 12 days by gavage. Subsequently, the animals were evaluated by echocardiography and euthanized, and the left ventricle was collected for biochemical and molecular analyses. TH modulates TLR4/NF-κβ expression in the infarcted hearts of rats and decreases xanthine oxidase expression. These effects were related to cardiac functional improvement after infarction. The cardioprotective effects of T3 and T4 seem to involve an anti-inflammatory action. [ABSTRACT FROM AUTHOR]

• A sensitive multi-step extraction and quantification method for thyroid hormones in lake sturgeon tissues was developed. • This method was validated in eggs, free embryos, larvae, and juvenile whole fish. • With modification, this method can be applied for other fish species. 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. [ABSTRACT FROM AUTHOR]

Background Mediastinal and central large vessels (T4) invasion by lung cancer is often difficult to assess preoperatively due to the limited accuracy of computed tomography (CT) scan of the chest. Esophageal ultrasound (EUS) can visualize the relationship of para-esophageally located lung tumors to surrounding mediastinal structures. Aim To assess the value of EUS for detecting mediastinal invasion (T4) of centrally located lung tumors. Methods Patients who underwent EUS for the diagnosis and staging of lung cancer and in whom the primary tumor was detected by EUS and who subsequently underwent surgical- pathological staging (2000–2016) were retrospectively selected from two university hospitals in The Netherlands. T status of the lung tumor was reviewed based on EUS, CT and thoracotomy findings. Surgical- pathological staging was the reference standard. Results In 426 patients, a lung malignancy was detected by EUS of which 74 subjects subsequently underwent surgical- pathological staging. 19 patients (26%) were diagnosed with stage T4 based on vascular (n = 8, 42%) or mediastinal (n = 8, 42%) invasion or both (n = 2, 11%), one patient (5%) had vertebral involvement. Sensitivity, specificity, PPV and NPV for assessing T4 status were: for EUS (n = 74); 42%, 95%, 73%, 83%, for chest CT (n = 66); 76%, 61%, 41%, 88% and the combination of EUS and chest CT (both positive or negative for T4, (n = 34); 83%, 100%, 100% 97%. Conclusion EUS has a high specificity and NPV for the T4 assessment of lung tumors located para-esophageally and offers further value to chest CT scan. [ABSTRACT FROM AUTHOR]

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 50,000 pg/mL. The limit of detection (LOD) was under 1 pg/mL while the limit of quantification (LOQ) was estimated as 10 pg/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. [ABSTRACT FROM AUTHOR]

Abstract The aim of this Study is to investigate whether the Iodine Supplementation Programme is successful or not. This Programme was implemented in Nyala to treat the Iodine deficiency. In this Study Nyala was selected to act as (a study area), due to the history of Iodine deficiency of this region, while Khartoum was selected to act as (a control area). 2000 samples were collected from Khartoum versus 450 samples from Nyala. Thyroxine (T 4) and triiodothyronine (T 3) levels in two regions were measured and performed by using radioimmunoassay (RIA), also the immunoradiometric assay (IRMA) used for measurement of thyroid stimulating hormone (TSH). The obtained results analyzed by using Statistical Package for Social Sciences (SPSS). (Coherent retrospective) used to determine differences between the study groups. The results of this study showed, there was no significant difference between the mean serum concentrations of T3 and TSH for Khartoum and Nyala. T4of Khartoum (117.93 ± 42.797) nmol/L and the mean serum T4 of Nyala (114.54 ± 45.526) nmol/L, the (P-value = 0.133).T3for Khartoum (1.8040 ± 0.99047) nmol/L and T3of Nyala (1.7307 ± 0.96508) nmol/L, the (P-value = 0.153). TSH for Khartoum (1.4480 ± 0.95807)mIU/Land the mean serum TSH of Nyala (1.4553 ± 1.0244) mIU/L, the (P-value = 0.885). The study showed a clear observation of improvement of hypothyroidism cases in Nyala while the ratio decreased from 64.09% to 0.6%. All the results were carried out according to normal range of Sudanese. The conclusion from this study the iodine supplementation programme is successful. The study recommends rising the health awareness among people by explain the severity of iodine deficiency, and continue in iodine supplementation programme, also establishment of monitoring system including monitoring the presence of iodized diets (sugar, salt, oils, and bread) in the markets. Finally, further studies are needed in other parts of Sudan to assess the size of iodine deficiency problem. [ABSTRACT FROM AUTHOR]

Studies have shown a cardioprotective role of thyroid hormones (THs) in cardiac remodeling after acute myocardial infarction (MI). However, there is no data in the literature examining the influence of TH administration on the aortic tissue in an animal model of MI. This study aimed to evaluate the effects of thyroid hormones on the aorta after MI. Male Wistar rats were divided into a sham group (SHAM), infarcted group (AMI), sham+TH (SHAMT) and AMI+TH (AMIT). After MI, the animals received T3 and T4 (2 and 8 μg/100 g/day, respectively) by oral gavage for 12 days. Later, the animals underwent echocardiography and euthanasia and the aorta was collected for molecular and biochemical analysis. T3 and T4 administration increased the expression of the pro-angiogenic proteins vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1α (HIF-1α) in the aorta of AMIT rats when compared with AMI. With respect to TH receptors, AMI rats presented a decrease in TRβ levels, which was prevented by the hormonal administration. In AMIT rats, both TRα and TRβ levels were increased when compared with the AMI group. Reactive oxygen species levels and NADPH oxidase activity were decreased in both treated groups when compared with the non-treated animals. TH administration after MI may improve angiogenic signaling in the aorta as well as the responsiveness of this vessel to T3 and T4. These positive effects in the aorta may result in additional protection for the cardiovascular system in the context of cardiac ischaemic injury. [ABSTRACT FROM AUTHOR]

Objective: To ascertain whether thyroxine (T4)-based screening programs for congenital hypothyroidism (initial measurement of total T4 [tT4] followed by thyroid stimulating hormone [TSH] measurement in patients with tT4 <10th percentile) identifies congenital hypothyroidism in all neonates with Down syndrome.Study Design: Retrospective cohort study of 159 neonates with Down syndrome, born during the period 1998-2007 were included. Screening test results were compared with those of the general population. All primary care physicians of these infants were contacted and infants' thyroid status verified.Results: tT4 concentrations in children with Down syndrome were significantly lower, and TSH higher than those in the general population; tT4 concentrations did not correlate with screening TSH concentrations. Twenty children with Down syndrome were treated with L-thyroxin within the first month of life although only 10 babies had been identified by the routine screening test.Conclusions: T4-based screening does not identify many cases of congenital hypothyroidism in neonates with Down syndrome. We recommend that neonates with Down syndrome be screened by simultaneous measurements of both tT4 and TSH. [ABSTRACT FROM AUTHOR]

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/100 g/day) and T4 (8 μg/100 g/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. [ABSTRACT FROM AUTHOR]

Introduction High dose thyroid (HDT) is included in major treatment guidelines for the treatment of bipolar disorders. Yet it is seldom used partly based on perceived cardiovascular risks. The cardiovascular risks of HDT are examined. Methods A literature search was conducted for the cardiovascular risks of HDT and for comparisons sake psychiatric medications. Case reports of atrial fibrillation (afib) associated with HDT are reported. Results While hyperthyroidism is a significant cardiovascular risk factor causing a 20% premature death rate, HDT treatment does not appear to be of significant cardiovascular risk. HDT differs from hyperthyroidism in significant ways. The sequela of hyperthyroidism are increasingly tied to autoimmune complications which are absent with HDT. Equating hyperthyroidism with HDT is incorrect. The five case reports of HDT treatment associated with afib were potentially caused by other factors. If HDT increases the risks of afib, monitoring for afib would minimizes the risk. Even in overt hyperthyroidism the risk of other arrhythmias are minimal. When compared to many psychiatric medications HDT is as safe or safer. Limitations There are no direct studies of cardiovascular risks of HDT for affective patients. High tolerance of a medication does not necessarily imply lack of risk. The five case reports were spontaneous, other cases may not have been reported. Conclusion The cardiovascular risks of HDT appear to be low. HDT is at least as safe as or safer than many psychiatric medications. It is effective and well tolerated. [ABSTRACT FROM AUTHOR]

Highlights: [•] This study evaluated thyroid hormones effects in oxidative stress after infarction. [•] T3 and T4 administration reduced ROS levels induced by myocardial infarction. [•] This treatment also normalized cardiac redox status and prevented lipid peroxidation. [•] This was associated with improved cardiac remodeling after the ischemic injury. [•] Thus oxidative stress may have a relevant part in T3 and T4 cardioprotective effects. [ABSTRACT FROM AUTHOR]

Abstract: Background: Non-small cell lung cancer (NSCLC) stage T4N0-1 or single nodal station IIIA-N2 are two stage III sub-groups for which the outcome of non-surgical therapy is not well known. We investigated the results of individualised isotoxic accelerated radiotherapy (INDAR) and chemotherapy in this setting. Methods: Analysis of NSCLC patients included in 2 prospective trials (NCT00573040 and NCT00572325) stage T4N0-1 or IIIA-N2 with 1 pathologic nodal station, treated with chemo-radiotherapy (CRT) using INDAR with concurrent or sequential platinum-based chemotherapy. Overall survival (OS) was updated and calculated from date of diagnosis (Kaplan–Meier). Toxicity was scored following CTCAEv3.0. To allow comparison with other articles the subgroups were also analysed separately for toxicity, progression free and overall survival. Results: 83 patients (42 T4N0-1 and 41 IIIA-N2) were identified: the median radiotherapy dose was 65Gy. Thirty-seven percent of patients received sequential CRT and 63% received concurrent CRT. At a median follow-up of 48months the median OS for T4N0-1 patients was 34months with 55% 2-year survival and 25% 5-year survival. For stage IIIA-N2 at a median follow-up of 50months the median OS was 26months with 2- and 5-year survival rates of 53% and 24%, respectively. Conclusion: Chemo-radiation using INDAR yields promising survival results in patients with single-station stage IIIA-N2 or T4N0-1 NSCLC. [Copyright &y& Elsevier]

Abstract: Previous work has shown that exposure to bisphenol A (BPA) can affect anxiety behavior. However, no studies have examined whether administration of this endocrine disruptor during the perinatal period has the potential to induce alterations in cognitive behavior in both adult males and females as assessed in an appetitive task. The goal of the current study was to determine whether exposure to different doses of BPA during early development alters performance on the 17-arm radial maze in adulthood in Long–Evans rats. Oral administration of corn oil (vehicle), 4μg/kg, 40μg/kg, or 400μg/kg BPA to the dams occurred daily throughout pregnancy, and the pups received direct oral administration of BPA between postnatal days 1–9. Blood was collected from offspring at weaning age to determine levels of several hormones (thyroxine, thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone). One male and one female from each litter were evaluated on the 17-arm radial maze, a working/reference memory task, in adulthood. Results indicated that after exposure to BPA at both 4 and 400μg/kg/day, rats of both sexes had decreased levels of FSH at weaning. There were no significant effects of BPA on performance on the radial arm maze in males or females. In conclusion, exposure to BPA during early development had modest effects on circulating hormones but did not affect performance on a spatial learning and memory task. [Copyright &y& Elsevier]

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 &y& Elsevier]

Summary: Background: Little is known of the association between thyroid hormones in the central nervous system and Alzheimer''s disease (AD). We determined thyroid hormone levels in serum and cerebrospinal fluid (CSF) in a well-defined homogeneous mono-center population. Methods: Fifty-nine consecutive patients under primary evaluation for cognitive impairment were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n =31), patients with stable MCI (SMCI, n =13), patients with other dementias (n =15), and healthy controls (n =19). Thyroid hormones in serum and CSF and AD biomarkers in CSF were analyzed using established immunochemical assays. Cognitive impairment was estimated using mini-mental state examination (MMSE). Results: Serum levels of free and total thyroxine (T4) and triiodothyronine (T3) were similar in all groups whereas a marginal increase in serum thyroid-stimulating hormone (TSH) level was observed in the AD patients. The CSF level of total T4 was decreased in patients with AD and other dementias compared to SMCI (both P =0.01) and healthy controls (both P =0.001), whereas CSF levels of TSH and total T3 were unchanged. In the total study population, CSF total T4 level correlated positively with MMSE score (r =0.26, P <0.05) and negatively with CSF total-tau (T-Tau) level (r =−0.23, P <0.05). Conclusion: Patients with AD as well as other dementias had signs of mild brain hypothyroidism, which could only to a small extent be detected in serum values. [Copyright &y& Elsevier]

Summary: The current study investigated the associations between thyroid stimulating hormone (TSH), free thyroxine (T4) and cognitive ability (general ability, memory and processing speed), in a large age homogenous sample (n =659) of generally healthy euthyroid older adults. Associations were considered both at baseline (mean age wave 1=69.5 years; SD=0.8 years) and approximately 3 years later (mean age wave 2=72.5 years; SD=0.7 years). Results indicated mean level decreases across waves in both TSH (t =10.99, p < 0.001) and T4 (t =34.55, p <0.001). There were no significant associations between TSH and T4 with any of the cognitive variables at either wave. There was no suggestion of non-linear associations. The lack of associations supports suggestions that the effects of thyroid hormones on cognition may be restricted to older individuals above a given threshold, and/or those with levels of thyroid hormones within the range defining clinical thyroid disorder. [ABSTRACT FROM AUTHOR]

Abstract: This study aims to assess the effect of different energy levels of restriction on physiological and genetic level adaptability. Eighteen adult nonpregnant does (average BW 33.56kg) were used in the present study. The ewes were divided into three groups, viz., GI (n=6; control), GII (n=6; 30% feed intake of control), GIII (n=6; 40% feed intake of control). The study was conducted for 40 days covering a period of two estrous cycles. Blood samples were collected every ten days interval. The parameters studied were allometric parameters (viz., body weight, and body condition) scoring and physiological responses (viz., respiration rate, pulse rate, and rectal temperature) biochemical parameters (glucose, albumin, creatinine, cholesterol), hormones (T3, T4, cortisol, leptin) and mRNA expression profile of leptin in peripheral blood mononuclear cells (PBMC). The nutritional stress significantly (P<0.05) affected most of the parameters. There was a significant (P<0.05) reduction in Body weight, Body condition score and. The physiological responses were significantly (P<0.05) affected. Among the biochemical parameters mean serum glucose first increased significantly (P<0.05) and then stabilized in GII whereas as there was no change in serum glucose levels in GIII. Serum albumin significantly (P<0.05) affected in late stages of study. There was no significant (P<0.05) changes in serum creatinine. Among hormonal parameters there was significant decrease in T3 in both the groups; T4 increased significantly in GII on 10th day and then stabilized whereas no changes was observed in GIII. Cortisol levels increased significantly (P<0.05) in both GII and GIII. There was a significant (P<0.05) reduction in serum leptin levels in GII but in GIII significant reduction was observed only 10th and 30th day of study. The mRNA expression was significantly (P<0.05) upregulated in GII on 30th day followed by a significant downregulation whereas in GIII significant (P<0.05) downregulation was only seen on 30th and 40th days. It can be concluded from our study that animals can maintain near physiological homeostasis even at 40% energy intake levels. The animals have innate physiological ability to survive periods of nutritional stress by adjusting leptin levels which are required for maintaining the physiological normalcy. [Copyright &y& Elsevier]

Abstract: A number of environmental chemicals have been reported to exhibit thyroid hormone-like activity. Since thyroid hormones play a crucial role in development, it is important to identify chemicals in the environment that are capable of endocrine disruption of thyroid hormone homeostasis. In order to detect thyroid hormone-like activity, the growth of pituitary cell lines has been commonly used as a sensitive marker, albeit with limited specificity to thyroid hormones. Reporter gene assays using the thyroid hormone responsive element (TRE) connected to the luciferase reporter gene have also been developed. Thus far however, this type of assay appears to have limited sensitivity compared to cell growth assays. In the present study, we developed a highly sensitive TRE reporter gene assay by using a pituitary cell line, MtT/E-2, and by culturing cells in a serum-free medium. Our assay was developed in order to detect T3 activity at a concentration of 10−11 M. This assay identified thyroid hormone-like activity from the antiarrhythmic drug, amiodarone, and from three anti-parasitic drugs, bithionol, closantel and rafoxanide, all commonly used in veterinary medicine. Thyroid hormone-like activity of these compounds was further confirmed by the induction of BCL3 gene expression in MtT/E-2, which is known to be regulated by thyroid hormones. Our improved assay was proved to be a sensitive tool for assessing thyroid hormone-like activity of environmental chemicals. [Copyright &y& Elsevier]

Abstract: Survival of seal pups may be affected by their ability to respond appropriately to stress. Chronic stress can adversely affect secretion of cortisol and thyroid hormones, which contribute to the control of fuel utilisation. Repeated handling could disrupt the endocrine response to stress and/or negatively impact upon mass changes during fasting. Here we investigated the effects of handling regime on cortisol and thyroid hormone levels, and body mass changes, in fasting male and female grey seal pups (Halichoerus grypus). Females had higher thyroid hormone levels than males throughout fasting and showed a reduction in cortisol midway through the fast that was not seen in males. This may reflect sex-specific fuel allocation or development. Neither handling frequency nor cumulative contact time affected plasma cortisol or thyroid hormone levels, the rate of increase in cortisol over the first five minutes of physical contact or the pattern of mass loss during fasting in either sex. The endocrine response to stress and the control of energy balance in grey seal pups appear to be robust to repeated, short periods of handling. Our results suggest that routine handling should have no additional impact on these animals than general disturbance caused by researchers moving around the colony. [Copyright &y& Elsevier]

Abstract: The objective of this study was to evaluate precision and establish a reference range in healthy guinea pigs for total plasma thyroxine (T4) using a point-of-care analyzer. One-hundred-nine (109) healthy pet and laboratory-housed guinea pigs were included in this study in which plasma T4 concentrations were measured on a point-of-care analyzer. Some of the samples were analyzed in duplicate and then compared using an intraclass correlation coefficient (r i ) and coefficient of variance to assess precision. Statistical analysis was performed to test for normal distribution of data and a reference range was established. Differences in subsets of the tested population were evaluated using t tests and analysis of variance. The r i was 0.95 and the coefficient of variance was 4.2%. Data were normally distributed and a reference range for plasma T4 of 2.26 μg/dL to 5.82 μg/dL was established. No significant differences between or among mean plasma T4 concentrations were found when sexes, housing type, and sampling protocol were compared. In addition, no significant difference was found between the mean plasma T4 concentrations of 2 age groups (2 months and 8 months). The overall precision of this testing modality was determined to be excellent, indicating that measuring plasma T4 with enzyme immunoassay on the point-of-care analyzer yields consistently repeatable results. This study successfully defined plasma T4 reference intervals specific to a point-of-care analyzer in normal guinea pigs. Our results showed that age (2 months and 8 months), sex, housing type, and sampling protocol have no significant effect on the mean plasma T4, although pet-housed guinea pigs had a wider reference interval than laboratory-housed guinea pigs. [Copyright &y& Elsevier]

Abstract: This study was conducted to determine the effect of different stress factors on some physiological measurements of Nile tilapia (Oreochromis niloticus). A total number of 160 Nile tilapia, the body weight ranging between 100 and 120g, were exposed to three stress factors of hypoxia, overcrowding and starvation for different periods 24, 72 and 144h. The results of cortisol level were 134.15, 144.27, 154.12ng/ml and 140.18ng/ml for control, hypoxia, overcrowding and starvation, respectively, while after 144h did not show significant difference among treatments compared with control group. In contrast, the values of T3 and T4 observed reduction with significant difference that T3 ranged between the highest value 122.12ng/ml for control group to lowest value of starvation group 94.35, 93.81 and 88.46ng/ml after 24, 72 and 144h. Also, similar trend of results observed in T4 and blood glucose among treatments. And the enzymatic activity of lactate dehydrogenise (LDH) increased in hypoxic group, while a significant reduction appeared in overcrowding and starved fish compared to control group. The pyruvate kinase (PK) activity decreased in hypoxic group but increased in other group. [Copyright &y& Elsevier]

Abstract: Microfabrication permits the incorporation of dense electrode arrays in microsystems and small volume diagnostic devices. However, the specific functionalization of arbitrary shape electrodes with different biomolecules remains a challenging issue. In the present work, the problem of fabricating closely spaced microelectrodes (20μm sensor diameter and 20μm-spaced interdigitated electrodes array) that can be modified selectively in order to create multi-analyte sensor arrays is addressed by employing a biomolecule friendly photolithographic procedure for the sequential immobilization of different biomolecules onto separated electrodes of the same array. The concept was demonstrated with selective detection of oligonucleotides for breast cancer gene mutation detection, the hormone T4 detected with specific antibodies and sarcosine and glucose detected with specific enzymes immobilized in two-analyte arrays in order to assure that the method is compatible with all the types of biorecognition molecules used in biosensors. Electrochemical techniques were used in this array, because of the low cost, high sensitivity and easy miniaturisation of these transducers. Although the array was composed of only two sets of electrodes, the results demonstrate that the method proposed is generic and could be used for patterning of electrochemical multi-analyte biosensors at even higher resolution. [Copyright &y& Elsevier]

Abstract: In experimental studies, it has frequently been observed that the homeostasis of thyroid hormones (THs) is affected by exposure to persistent organic pollutants (POPs), such as dioxins and PCBs. In man, similar effects have been indicated in several epidemiological studies. In order to investigate the possible effect on THs at low background exposures found among the Swedish population the following study was performed. Primiparous women (n =395) in the Uppsala region were recruited between 1996 and 1999. Of these, 325 mothers agreed to donate a serum sample in late pregnancy and breast milk was obtained from 211 women 3weeks after delivery. Babies were sampled for blood at 3weeks (n =150) and 3months (n =115) after birth. In connection to the sampling, questions on personal characteristics were asked. Levels of low (tri- to penta-) chlorinated PCB, di-ortho PCB, p,p′-DDE, (mono-ortho) PCB TEQ and PCDD/DF TEQ were monitored in breast milk and in mother''s blood (not PCDD/DF). The results showed that the measured TH levels (thyroid-stimulating hormone — TSH, total tri-iodothyronine — TT3, free thyroxine — FT4) in mothers and children were within the reference range. Some significant associations were seen between POP exposures and TH levels in mother or child after simple regression analysis. Following adjustment for important confounding factors, the significant associations mostly disappeared. However, significantly decreasing TT3 levels with increasing prenatal low-chlorinated PCB exposure were still seen in 3week old children, and on TT3 in mothers exposed to PCDD/DF. In conclusion, the study clearly shows the importance of adjustment for important confounding factors in the analysis of possible associations between POP exposure and hormonal effects. The remaining associations are weak in both children and mothers and the clinical consequences of these alterations are uncertain. When comparing studies that investigate associations between TH levels and POP levels during the perinatal stage, no obvious between-study concordance was seen regarding the critical dose for hormonal effects to occur. [Copyright &y& Elsevier]

Abstract: Background: Multiple organ resection for locally advanced (assumed T4) gastric cancer is associated with high morbidity and mortality. Our aim was to evaluate the efficacy of these surgeries with regard to surgical morbidity, mortality, and survival. Methods: Fifty-six patients underwent potentially radical gastrectomy combined with invaded organ resection. Early and late results of multiorgan resection and clinicopathologic factors influencing these results were evaluated. Results: Forty patients (71.4%) received 1 additional organ resection and 16 patients (28.6%) received 2 or more additional organ resections. Postoperative morbidity and mortality was 37.5% and 12.5%, respectively. Resection of 2 or more additional organs increased postoperative morbidity and advanced age increased mortality. The 1- and 3-year survival rates were 53.3% and 28.1%, respectively. Advanced age, lymph node metastasis, and resection of more than 1 additional organ were significant prognostic factors for survival. Conclusions: For patients with locally advanced gastric carcinoma, multiple organ resection is worthwhile with careful patient selection. [Copyright &y& Elsevier]

Abstract: Background: Thyroxin (T4) plays an important role in the regulation of the rate of metabolism of proteins, fats, and carbohydrates. Congenital hypothyroidism, an inherited deficiency of thyroid hormones, is screened in newborns using a variety of methods that include total T4 or thyroid stimulating hormone (TSH). Some laboratories measure either total T4 or TSH as a means of detecting infants with hypothyroidism with a subset that analyzes both total T4 and TSH as a primary screen or a combination of primary and secondary screens. Methods: We have developed a new MS/MS method that measures T4 from a filter paper blood spot following methanol extraction using the essentially the same method as MS/MS analysis of amino acids. Product ion spectra show a transition of 833.8→731.8 (102 Da). An SRM for T4 and 13C6–T4 was added to the MS/MS analysis of acylcarnitines and amino acids. Results: Analysis of T4 by MS/MS compares well with the immunoassay. The mean of 10,225 newborn screening specimens was 14.4 μg/dl (range 2.4–33) for MS/MS and 16.9 μg/dl (range 1.4–71.8) for AutoDELFIA. The MS/MS assay was linear with a correlation coefficient of 0.998. Regression analysis of MS/MS with the AutoDELFIA had a slope of 0.7, a y-intercept of 3.25, and a correlation coefficient of 0.727. We determined a MS/MS detection limit of 0.97 μg/dl and a lower LoQ (limit of quantification) of 2 μg/dl. Conclusion: This method may provide a cost effective means of analyzing both T4 and TSH by consolidating a T4 analysis into the MS/MS panel. [Copyright &y& Elsevier]

Abstract: We examined the effect of acclimation to moderate hyperthermic environment on the ACTH, TSH, T3, T4 and corticosterone level, as well as the relative weight of hypophysis, thyroid and adrenal glands in streptozotocin-diabetic rats. Increased activity of the hypothalamo-pituitary-adrenocortical (HPA) axis has been demonstrated in diabetic animals, whereas insulin treatment restores the changes. Heat acclimation reduces the level of ACTH and corticosterone in control animals and moderates the hormonal disturbances caused by diabetes. Simultaneously, our study revealed impairment in the activity of the hypothalamo-pituitary-thyroid (HPT) axis. Acclimation to 35±1°C resulted in significantly lower T3 and T4 levels in control, diabetic and insulin-treated animals. Relative weight of the hypophysis, thyroid and adrenal glands is decreased in heat-acclimated rats. Our assumption is that there might be a cross tolerance between diabetes and heat acclimation on a hormonal level. [Copyright &y& Elsevier]

• A single nucleotide polymorphism near the iodothyronine deiodinase 2 (DIO2) gene in fetal pigs was associated with variation in serum total T4 level and size of the proximal humeral ossification center following maternal PRRSV-2 infection. Porcine reproductive and respiratory syndrome (PRRS) is one of the most common viral diseases affecting the global pork industry, causing significant economic loss in breeding herds and growing pigs. Control is challenging and genomic interventions can potentially yield alternative strategies to control PRRS virus (PRRSV) infection. We previously conducted a genome-wide association study to broaden our understanding of host genetics of fetal responses following maternal PRRSV infection and found that an intergenic single nucleotide polymorphism (SNP) near the DIO2 gene encoding the type II iodothyronine deiodinase, was significantly associated with fetal viability in response to maternal PRRSV infection. To determine the potential effect of this SNP on fetal outcomes including fetal viability, survival, growth and developmental characteristics in an independent pregnant gilt challenge model, we produced balanced homozygous fetal populations comprised of either the SNP's A or B allele. We assessed fetal viral loads in placenta, serum, and thymus, serum thyroid hormone levels, and growth and bone development by genotype at the SNP site. Unexpectedly, the BB genotype was not associated with greater odds ratio of fetal viability but was significantly related to reduced serum T4 level and increased area of the proximal humeral secondary ossification center (PHOC). To our knowledge, this is the first report of the variation in the genomic region influencing fetal T4 level and PHOC area in response to PRRSV infection. These results might implicate a functional effect of the genomic region on fetal thyroid hormone metabolism, which is partly involved in fetal bone biology during maternal PRRSV infection. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Present study examines effects of curcumin and vitamin E on oxidative stress parameters, antioxidant defence enzymes and oxidized (GSSG) and reduced glutathione (GSH) levels in testis of l-thyroxine (T4)-induced hyperthyroid rats. The oxidative stress in T4-treated rat testis was evident from elevation in oxidative stress parameters such as lipid peroxide and protein carbonyl contents, decrease in superoxide dismutase (SOD) and catalase (CAT) activities and increase in glutathione peroxidase (GPx) activity. This is accompanied with decrease in number and mortality of epididymal sperms. When the T4-treated rats were fed with vitamin E and/or curcumin, the lipid peroxide and protein carbonyl contents in crude homogenates of testes decreased to normal level. Treatment of curcumin and/or vitamin E to T4-treated rats resulted in elevation of SOD level in postmitochondrial fraction (PMF) and mitochondrial fraction (MF) and CAT in PMF, with decreased GPx activity in MF. However, curcumin or vitamin E was unable to change GPx activity alone but in together they elevated the GPx in PMF of T4-treated rat testis. Both the antioxidants are incapable of producing significant changes in GSH:GSSG ratio of PMF of T4-treated rats. In MF, GSH:GSSG ratio elevated and decreased respectively by curcumin and vitamin E treatments to T4-treated rats, however, in together these antioxidants caused an elevated GSH:GSSG ratio with a value less than when vitamin E given alone to T4-treated rats. Vitamin E not the curcumin elevates total sperm count and percentage of live sperm impaired by hyperthyroid state. In summary, both vitamin E and curcumin are efficient in protecting testis from oxidative stress generated by T4 mainly in restoring antioxidant enzymes to the level of euthyroid animals up to some extent but vitamin E is more efficient than curcumin. [Copyright &y& Elsevier]

Abstract: Although partial penetration of ultrafiltration membranes by viruses and bacteria is well documented, there is no satisfactory explanation for the phenomenon. The current study seeks a possible explanation by studying the retention of viruses at different transmembrane pressures (TMPs). In contrast to previous predictions, higher TMPs lead to reduced virus retention levels. Based on indirect evidences it is proposed that the penetration occurs because of the formation during operation, rather than the initial presence, of abnormally large pores. It is therefore suggested that since pore enlargement is induced by high TMPs, high virus retention levels can be obtained only at low TMP values. [Copyright &y& Elsevier]

Abstract: We have taken advantage of the availability of the genome sequences of a collection of large and giant viruses infecting bacteria (T4 family) and eukaryotes (NCLDV group) to assess some of the evolutionary forces which might have shaped their genomes. Despite having apparently different ancestors, these two groups of viruses are affected by convergent evolutionary forces. Both types of virus probably originated from a simple and ancient viral ancestor with a small subset of 30–35 genes encoding replication and structural proteins. The genome size and diversity of the descendants most likely grew progressively by (i) lineage-specific gene duplications, (ii) lateral gene transfers of cellular genes and (iii) accretion of diverse families of mobile genetic elements. These results argue against the hypothesis that giant viruses derive from a regressive cell. [Copyright &y& Elsevier]

The extensive body of literature regarding the interaction of polychlorinated biphenyls (PCBs) with transcription factors (receptors) has great value to understand similarities and distinctions and in formulating hypotheses regarding the activity of polybrominated diphenyl ethers (PBDEs) toward those same receptors. Our goal is to present the most comprehensive overview of PBDE effects on AhR, CAR, PXR, ER, AR, PR, DHT, TH, T3, T4 and IGF, as well as hypothetical biological activities of PPAR, RyR, GR and GABA. Aside the influence of the conformation of the ligand, we discuss its constitution influencing the binding affinity: size and polarizability, hydrophilicity, Gibbs free energy of solvation, inductive and mesomeric effects. We evaluate the techniques to determine the biologically relevant conformation of these halogenated hydrocarbons, including computation methods, X-ray and microwave spectroscopy. A novel fluoro-tagged ligand approach holds promise as tools for illuminating the steric and electronic effects in ligand–receptor interaction. Based on our assessment, we predict that PBDEs do not exhibit AhR activity themselves, but impurities are responsible for these effects. [Copyright &y& Elsevier]

Abstract: Objectives: Concurrent chemoradiotherapy (CCR) was given for the previously untreated T4 hypopharyngeal and laryngeal squamous cell carcinoma patients and the response and survival rates were evaluated. Patients and methods: A total of 23 patients, namely, 15 for hypopharynx and 8 for larynx were eligible. These patients were given cisplatin and 5-fluorouracil based chemotherapeutic regimens with conventional radiotherapy for a total dose of 66.6–70.2Gy. Results: Ten out of the 15 hypopharyngeal carcinoma patients and 4 out of the 8 laryngeal carcinoma patients showed a complete response at the primary sites. The 5-year disease-specific survival rate was 59.4% in all the patients, 51.9% in the hypopharyngeal carcinoma patients, and 71.0% in the laryngeal patients. Seven out of the 12 resectable hypopharyngeal carcinoma patients and 4 out of 8 laryngeal carcinoma patients were able to do without total laryngectomy. Conclusions: Based on these results, the survival rate in the hypopharyngeal and laryngeal T4 carcinoma patients treated by CCR seems to be satisfactory and the possibility of organ preservation for the advanced patients is indicated. [Copyright &y& Elsevier]

Abstract: Development of the thyroid gland of the Japanese eel (Anguilla japonica) was studied with the use of tank-reared fish. A single thyroid follicle was first found in larvae at 29 days post hatching (dph), total length (TL) 12 mm. Until reaching 25 mm in TL (100 dph), leptocephali had one or two follicles per individual. The inner colloid of the follicles was weakly immuno-positive against the anti-thyroxine (T4) antibody. The number of thyroid follicles and the immunoreactivity later increased as the larvae grew. Thyroid hormones (TH) T4 and triiodothyronine (T3) were not detected in premetamorphic larvae by radioimmunoassays, but became detectable during metamorphosis. The maximum level of T4 was seen in fish at the end of metamorphosis and in just-metamorphosed juveniles, whereas T3 reached the highest level during metamorphosis and declined toward the end of metamorphosis. The results indicated that the thyroid gland first became active during metamorphosis in the development of eel. [Copyright &y& Elsevier]

Abstract: Octyl-methoxycinnamate (OMC) is one of the most frequently used UV-filters in sunscreens to protect the skin against the noxious influence of UV radiation. Recently, OMC was suspected to act as an “endocrine active chemical” (EAC) with estrogenic actions. While EACs have been investigated thoroughly for interference with reproductive function in mammalians, surprisingly little efforts have been made to investigate an interference of EACs with the hypothalamo-pituitary–thyroid (HPT) axis despite the expression of estrogen receptors in all parts of this axis. Therefore, we conducted an in vivo study with ovariectomised rats treated for 5 days with different doses of OMC or 17β-estradiol (E2) as a control. Determined parameters comprised serum levels of TSH, T4 and T3, hypothalamic TRH mRNA expression, protein-expression of the sodium–iodide-symporter (NIS) and the TSH receptor and the activities of thyroid peroxidase (TPO) in the thyroid and the T3-responsive hepatic type I 5′deiodinase (Dio1) in the liver. While E2 did not affect TSH-, T4- or T3-levels, OMC caused a dose-dependent decrease of serum concentrations of all of these hormones. TRH expression remained unaffected, while in the thyroid, expression of the TSH receptor but not of NIS was stimulated by OMC. TPO activity was unaltered but Dio1 activity was reduced by OMC. Thus, our results demonstrate a non-estrogenic interference of OMC within the rodent HPT axis with inadequate feedback response to impaired thyroid hormone status, indicated by decreased serum thyroid hormone and hepatic Dio1 levels. [Copyright &y& Elsevier]

Several transporter families that can transport thyroid hormones have been identified. One of these is represented by the organic anion transporting polypeptide (OATP) gene superfamily, classified within the solute carrier family SLCO. In humans, eleven different OATPs are expressed in various tissues, including the liver, kidney, brain, lung, intestine and placenta. They mediate sodium-independent transport of a variety of amphipathic organic compounds, including thyroid hormones, bile acids, steroid hormones and their conjugates, linear and cyclic peptides, prostaglandins, numerous drugs and other xenobiotics. OATP1C1, which is expressed in the blood–brain barrier and testes, is the thyroid hormone transporter with the highest apparent affinity, with Km values of 90.4nM for thyroxine (T4) and 127.7nM for reverse T3 (rT3) transport, and could be essential for thyroid hormone delivery to the developing brain. OATP4A1 is expressed in the placenta and could be important for maternal thyroid hormone transport to the developing fetus. [Copyright &y& Elsevier]

Abstract: Thyroid hormone insufficiency leads to impaired neurogenesis, behavioral alterations and cognitive deficits. Thyroid hormone receptors, expressed in brain regions involved in these behaviors, mediate the effects of thyroid hormone deficiency or excess. To determine the contribution of thyroid hormone receptor alpha (TRα) in these behaviors, we examined the behavior of euthyroid as well as hypo- and hyperthyroid mice lacking all isoforms of the TRα (TRαo/o). The hypothyroxinemic TRαo/o mice demonstrated behavioral inhibition, manifested in decreased activity and increased anxiety/fear in the open field test (OFT) and increased immobility in the forced swim test (FST) compared to C57BL/6J mice. TRαo/o mice also showed learning and recall impairments in the Morris water maze (MWM), which were exaggerated by hypothyroidism in TRαo/o mice. These impairments were concurrent with increased thigmotaxis, suggesting an increased anxiety-like state of the TRαo/o mice in the MWM. Expression of genes, known to be involved in processes modulating learning and memory, such as glucocorticoid receptor (GR), growth-associated protein 43 (GAP-43) and neurogranin (RC3), were significantly decreased in the hippocampus of TRαo/o mice. GR expression was also decreased in the frontal cortex and amygdala of TRαo/o mice, indicating that expression of GR is regulated, probably developmentally, by one or more isoforms of TRα in the mouse brain. Taken together these data demonstrate behavioral alterations in the TRαo/o mice, indicating the functional role of TRα, and a delicate interaction between TRα and TRβ-regulated genes in these behaviors. Thyroid hormone-regulated genes potentially responsible for the learning deficit found in TRαo/o mice include GR, RC3 and GAP-43. [Copyright &y& Elsevier]

Abstract: Migration and superoxide anion (O2 −) generation were studied in polymorphonuclear leukocytes (PMNs) from 14 athyreotic patients, previously treated by total thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma, and from age- and sex-matched euthyroid healthy controls. Patients were studied twice: in hypothyroidism (visit 1) and after TSH-suppressive L-T4 replacement therapy (visit 2). Random migration and N-formyl-Met-Leu-Phe (fMLP) 0.1-μM induced chemotaxis were similar in cells from patients at both visit 1 and visit 2 and from healthy controls. On the contrary, resting O2 − generation in cells from patients was significantly lower than control values, both at visit 1 and 2. At visit 1, fMLP 0.1 μM-induced O2 − generation was significantly lower than control values, while phorbol-myristate acetate (PMA) 100-ng/ml induced O2 − generation was similar in cells from patients and from controls. At visit 2 both responses increased, resulting in fMLP-induced O2 − generation superimposable to control values and PMA-induced O2 − generation significantly higher with respect to both visit 1 and cells from controls. In vitro exposure of PMNs from healthy subjects to L-T4 did not affect O2 − generation in resting cells, and significantly increased that induced by fMLP or PMA only at high, supra-physiological concentrations. Neither TSH nor T3 had significant effects at any of the concentrations tested. The present results document the existence of a correlation between thyroid status and oxidative metabolism of human PMNs, which is however unlikely to depend upon a direct action of thyroid hormones on these cells. [Copyright &y& Elsevier]

Abstract: The thyroid gland is under the control of thyroid stimulating hormone (TSH) from the pituitary. It secretes thyroxine (T4) and triiodothyronine (T3). Iodine is essential for the synthesis of thyroid hormones. T4 is probably converted to T3 in peripheral tissues. Thyroid hormones have a role in growth and development but their principal effect is the control of basal metabolic rate. Deficiency or excess affects all the tissues of the body, reducing or increasing the metabolic rate, resulting in hypothermia or hyperthermia, respectively. Deficiency during development produces mental retardation. Lack of iodine leads to thyroid swelling (goitre) caused by continuing stimulation by TSH. Calcium is one of the most tightly controlled ions in the body; abnormalities can produce muscle paralysis. Bone is the major store of calcium. Calcium reabsorption by the kidney is controlled by parathyroid hormone (PTH) produced by the parathyroid glands, which lie in the posterior part of the lobes of the thyroid gland. PTH secretion is controlled by blood calcium concentrations. Phosphate metabolism is intimately bound up with the control of calcium levels, as is the metabolism of vitamin D, which stimulates the absorption of calcium from the gastrointestinal tract and, in part, from the kidney. [Copyright &y& Elsevier]

Abstract: In this study, the effects of exposure to a 900megahertz (MHz) electromagnetic field (EMF) on serum thyroid stimulating hormone (TSH) and triiodothronine–thyroxin (T3–T4) hormones levels of adult male Sprague–Dawley rats were studied. Thirty rats were used in three independent groups, 10 of which were control (without stress and EMF), 10 of which were exposed to 900MHz EMF and 10 of which were sham-exposed. The exposures were performed 30min/day, for 5days/week for 4 weeks to 900MHz EMF. Sham-exposed animals were kept under the same environmental conditions as the study groups except with no EMF exposure. The concentration of TSH and T3–T4 hormones in the rat serum was measured by using an immunoradiometric assay (IRMA) method for TSH and a radio-immunoassay (RIA) method for T3 and T4 hormones. TSH values and T3–T4 at the 900MHz EMF group were significantly lower than the sham-exposed group (p &#60;0.01). There were no statistically significant differences in serum TSH values and T3–T4 hormone concentrations between the control and the sham-exposed group (p >0.05). These results indicate that 900MHz EMF emitted by cellular telephones decrease serum TSH and T3–T4 levels. [Copyright &y& Elsevier]