TH Levels Research Articles

The discussion of the relationship between cardiopulmonary bypass and postoperative thyroid function changes in pediatric congenital heart disease, and the analysis of oral thyroid hormone therapy and cardiac prognosis.

This study aims to investigate the relationship between CPB factors and changes in TH levels in postoperative patients and the effect of oral levothyroxine sodium tablets on outcomes in patients with postoperative TF abnormalities. Select patients who underwent CHD surgery between September 2017 and September 2023 and were aged 13 years or younger. The relationship between CPB and postoperative TF changes and the influencing factors were analyzed. In addition, patients with different diseases and ages were divided into the medication group and the non-medication group. The primary outcome was postoperative ejection fraction (EF), and the secondary outcomes were PICU hospitalization days and total hospital cost. Seven hundred 53 patients were included. The longer the CPB time and ACC time, the lower the postoperative triiodothyronine (T3) and thyroxin (T4) levels (p < 0.001 and p < 0.001). The longer the CPB time, the more pronounced the postoperative T3 level abnormality (p < 0.001). The longer the CPB time, ACC time, and DHCA time, the more pronounced the postoperative T4 level abnormalities (p < 0.001 and p < 0.001 and p = 0.046). The postoperative EF of patients in the medication group was slightly higher than that of the non-medication group, and the EF before discharge was significantly higher than that of the non-medication group (p = 0.021, p = 0.015, and p = 0.024). Postoperative PICU days in the medication group [3.0 (2.0,7.0) versus4.0 (2.0,10.0), p = 0.020] were shorter than the non-medication group, and the proportion of ≤ 5days was more [154 (66.1%) versus304 (58.5%), p = 0.047]. The total hospitalization cost was slightly lower in the medication group (p < 0.05). The duration of CPB, ACC, and DHCA in the open surgery process for CHD affects patients' thyroid function in the postoperative period. In our study, we found that oral levothyroxine sodium tablets are beneficial to the children's postoperative recovery.

Evaluation of return cooling water reuse in the wet cooled power plant to minimise the impact of water intake and drainage

The treatment and reuse of industrial water is a matter of great interest, given the severe shortage of water resources. It is widely acknowledged that power plants, particularly wet-cooled power plants, consume a significant amount of water. Therefore, research on the circulating cooling system (CCS) and the treatment of the return cooling water is of utmost importance. This study examined data on CCS inlet (water body), make up, and cooling water parameters, calculated a water balance, and predicted the hydrochemical quality of cooling tower blowdown water (CTBD). The study was conducted for an operating power plant to propose an effective treatment scheme for the return of CTBD to the process cycle. Additionally, it evaluated the possibility of recycling CTBD in the clarifier through laboratory modeling. Therefore, based on the results of this study, an effective treatment scheme is proposed to return CTBD to the technological cycle to ensure environmental sustainability. Recycled water was used as the water supply for the cooling tower, and a lime softening treatment was applied to clean the CTBD. According to the results, it is possible to recover quality indicators from a portion of the return cooling water after lime softening treatment. The novelty of this study lies in the successful demonstration of a lime softening regime that enables the blending of up to 25 % CTBD with make up water, without necessitating an increased CaO dose. This regime maintains TH levels at 2.2 mg-eq/dm³ and ensures that the discharge velocity of 0.7 m/s remains within regulatory standards. Additionally, it maintains standard concentrations of chloride (Cl⁻) and sulfate (SO₄²⁻) in CTBD at 200 mg/dm³ and 250 mg/dm³, respectively.

Homologous Temperature Regulated Hierarchical Nanoporous Structures by Dealloying.

Nanoporous metals, fabricated via dealloying, offer versatile applications but are typically limited to unimodal porous structures, which hinders the integration of conflicting pore-size-dependent properties. A strategy is presented that exploits the homologous temperature (TH)-dependent scaling of feature sizes to generate hierarchical porous structures through multistep dealloying at varied TH levels, adjusted by altering dealloying temperatures or the material melting points. This technique facilitates the creation of monolithic architectures of bimodal porous nickel and trimodal porous carbon, each characterized by well-defined, self-similar bicontinuous porosities across distinct length scales. These materials merge extensive surface area with efficient mass transport, showing improved current delivery and rate capabilities as electrodes in electrocatalytic hydrogen production and electrochemical supercapacitors. These results highlight TH as a unifying parameter for precisely tailoring feature sizes of dealloyed nanoporous materials, opening avenues for developing materials with hierarchical structures that enable novel functionalities.

Total triiodothyronine level associated with disease severity for patients with emergent status

Thyroid hormones are metabolic indicators to evaluate the physical condition of emergency hospitalized patients, while the relationship between total triiodothyronine and the severity of emergency inpatients is still unclear. To explore the thyroid function levels of inpatients in emergency ward and the status of combined Nonthyroidal illness syndrome (NTIS), and to emphasize the importance of thyroid hormone examination for non-endocrinology inpatients. According to thyroid function of inpatients in emergency ward, they were divided into NTIS group and non-NTIS group, the hematological characteristics and TH levels of each group were analyzed. Based on clinical diagnoses, the hospitalized patients were divided into three major groups, namely infection group, non-infection group and impaired organ function group. Among them, infection group was further divided into sepsis group, lung infection group and local infection group, altogether five groups. The thyroid function levels and low values in each group were evaluated, and the correlation between hormone levels and inflammatory factors, nutritional indicators and the relationship with the risk of death was discussed. The inpatient rate in emergency ward complicated with NTIS was 62.29%, T3 was the most sensitive index of NTIS, followed by FT3. Compared to non-NTIS group, the NTIS group had an increased risk of death. The sepsis group and impaired organ function group had the highest rates of complicated NTIS, reaching 83.33% and 78.12% respectively. Spearman's correlation analysis implied T3/T4/FT3 levels were positively correlated with ALb and PLT (except T4), and negatively correlated with CRP, D-Dimer, IL-6 and Fer. The Receiver Operating Curve (ROC) and Area under the curve (AUC) showed T3 levels alone were strongly associated with the risk of death (AUC 0.750; 95% CI 0.673–0.828; P < 0.001). T3 is the most sensitive indicator for emergency patients, followed by FT3. The decrease of T3 level has a good predictive value for mortality risk. Thyroid function should be monitored in critically ill patients.

Chronic pain predicts a worse response to depression treatment, regardless of thyroid function or psychotropics prescribed

BackgroundChronic pain (CP) and thyroid hormones' (TH) abnormalities are associated with depression, but the impact of pain and TH fluctuation on the response to depression treatment is uncertain. MethodsEighty-eight patients with major depression were evaluated before and after 6 months of specific treatment, through scales of symptoms' severity (HAM-D-17), psychomotor disturbance (CORE), and quality of life (WHOQOL-Bref). We reviewed psychiatric medications and measured TSH, T3 and T4. We used Generalized Estimating Equations to assess the interaction effect between CP and treatment time on depression severity and TH levels, and Bonferroni to compare means. Results47.7 % of the patients had CP. Patients with and without CP did not differ at baseline. At follow-up, those with CP experienced a more modest decrease in symptoms' severity and no improvement in any domain of psychomotor disturbance, contrasting with a decrease of over 40 % from the baseline values of CORE in patients without CP (non-CP). Initial and final scores were respectively: HAM-D CP 24.06 and 19.3, Δ = -4.75; HAM-D non-CP 22.92 and 14.7, Δ = -8.21; CORE CP 5.36 and 5.24, Δ = -0.12; CORE non-CP 5.8 and 3.22, Δ = -2.57. There was no interaction with TH or life quality. Model adjustments for psychotropic drugs received and sensitivity analysis excluding somatic symptoms from severity scales did not impact the results. LimitationsFindings may not replicate in mildly depressed patients from primary care. Pain scales were not applied. ConclusionsIndividuals with chronic pain showed a suboptimal response to depression treatment, regardless of the medications used or TH levels.

Effect of the Fetal THRB Genotype on the Placenta.

Pregnant women with mutations in the thyroid hormone receptor beta (THRB) gene expose their fetuses to high TH levels shown to be detrimental to a normal fetus (NlFe) but not to an affected (AfFe) fetus. However, no information is available about differences in placental TH regulators. To investigate whether there are differences in placentas associated with a NlFe compared to an AfFe, we had the unique opportunity to study placentas from two pregnancies of the same woman with THRB mutation G307D. One placenta supported a NlFe while the other an AfFe. Sections of placentas were collected and frozen at -80°C after term delivery of NlFe and AfFe. Two placentas from healthy women of similar gestational age were also obtained. The fetal origin of the placental tissues was established by gDNA quantitation of genes on the X and Y chromosomes and THRB gene. Expression and enzymatic activity of deiodinases 2 and 3 were measured. The following genes expression was also quantitated: MCT10, MCT8, LAT1, LAT2, THRB, THRA. The placenta carrying the AfFe exhibited a significant reduction of deiodinase 2 and 3 activities as well as the expression of the thyroid hormone transporters MCT10, LAT1 and LAT2 and the THRA. Here, we present the first study of the effect of fetal THRB genotype on the placenta. Though limited by virtue of the rarity of THRB mutations and sample availability, we show that the fetal THRB genotype influences the levels of thyroid hormone regulators in the placenta.

Interferencija TSH i tiroidnih hormona posle vakcine za Covid-19 ili Covid-19 infekcije

Immunoassays are commonly used to measure thyroid-stimulating hormone (TSH) and thyroid hormone levels (TH). However, interference in these immunoassays may lead to the misinterpretation of patient results and incorrect therapeutic decisions. Analytical interference can occur following exposure to animals, infections, vaccination, in autoimmune diseases, or without an identified cause. Analytical interference associated with COVID-19 exposure has been observed in D-dimer measurements. A dilution test was used to confirm interference in the measurement of TSH and TH levels. In three patients, interference in TSH and TH levels was detected after COVID-19 infection or vaccination. Conclusions: Owing to the high number of infected and vaccinated individuals, we can expect an increase in the prevalence of interference in immunometric methods.

Assessment of groundwater geochemistry for drinking and irrigation suitability in Jaunpur district of Uttar Pradesh using GIS-based statistical inference.

The quality of groundwater in the Jaunpur district of Uttar Pradesh is poorly studied despite the fact that it is the only supply of water for both drinking and irrigation and people use it without any pre-treatment. The evaluation of groundwater quality and suitability for drinking and irrigation is presented in this study. Groundwater samples were collected and analysed by standard neutralisation and atomic emission spectrophotometry for major anions (HCO3-, SO42-, Cl-, F-, NO3-), cations (Ca2+, Mg2+, Na+, K+), and heavy metals (Cd, Mn, Zn, Cu, and Pb). The geographic information system (GIS) and statistical inferences were utilised for the spatial mapping of the groundwater's parameters. The potential water abstraction (i.e. taking water from sources such as rivers, streams, canals, and underground) for irrigation was assessed using the sodium absorption ratio (SAR), permeability index (PI), residual sodium carbonate (RSC), and Na percentage. According to the findings, the majority of the samples had higher EC, TDS, and TH levels, indicating that they should be avoided for drinking and irrigation. The positive correlation coefficient between chemical variability shows that the water chemistry of the studied region is influenced by geochemical and biological causes. According to the USSL (United States Salinity Laboratory) diagram, most of the samples fall under the C2-S1 and C3-S1 moderate to high salt categories. Some groundwater samples were classified as C4-S3 class which is unfit for irrigation and drinking. This study suggests that the groundwater in the study area is unfit for drinking without treatment. However, the majority of the samples were suitable for irrigation.

Relationships Between Maternal Selected Metals (Cu, Mg, Zn and Fe), Thyroid Function and Blood Glucose Levels During Pregnancy

The aim of this study were to understand the intake of selected metals (copper (Cu), zinc (Zn), iron (Fe) and magnesium (Mg)) during pregnancy; to detect serum Cu, Mg, Zn and Fe levels in pregnant women; to analyze the relationships among the selected metals, maternal thyroid function and fasting blood glucose (FBG) levels; to investigate the impact of the selected metals and maternal thyroid function on the risk of gestational diabetes mellitus (GDM); and to provide clinical value for the rational intake of the selected metals and iodine during pregnancy to ensure normal fetal development. The population was recruited from pregnant women presenting to the obstetrics outpatient clinic of Shanxi Provincial People's Hospital (February 2021 to April 2022). Selected metal, thyroid hormone (TH (free thyroxine (FT4), free tri-iodothyronine (FT3), and thyroid-stimulating hormone (TSH)) and FBG levels were measured in pregnant women during early, middle and late pregnancy. Covariance analysis was used to analyze the overall trends in selected metal, TH and FBG levels during pregnancy, and binary logistic regression models were used to assess the impacts of the selected metals and thyroid function on the risk of GDM. In addtion, the potential mediation effects of thyroid functions were explored in the mediation analyses. A total of 65 pregnant women were included in this study. Regression models showed that maternal Mg and Cu levels were positively associated with the risk of GDM, conversely, logFT4 was negatively associated with the risk of GDM. Mediation analyses suggested that the associations between the selected metals (Zn, Cu and Mg) and GDM might be mediated by FT3 levels, and that the Cu-GDM and Zn-GDM association could be explained by FT4 levels. Additionally, the Zn-GDM association could also potentially be mediated by the FT3/FT4 ratio. Our findings suggest that Mg, Cu and FT4 levels may act as influencing factors for the development of GDM, and maternal FT3, FT4 and the FT3/FT4 ratio might be the potential mediators of the associations between the selected metals and GDM risk during pregnancy.

Feasibility study for a downsized comparative thyroid assay with measurement of brain thyroid hormones and histopathology in rats: Case study with 6-propylthiouracil and sodium phenobarbital at high dose

Concern has been raised that thyroid hormone disruptors (THDs) may potentially interfere with the developing brain, but effects of mild suppression of maternal THs by environmental contaminants on neonatal brain development are not fully understood. The comparative thyroid assay (CTA) is a screening test for offspring THDs, but it requires several animals and is criticized that reliance on serum THs alone as predictive markers of brain malfunction is inadequate. To verify feasibility of the downsized CTA but additional examination of brain THs levels and histopathology, we commenced internal-validation studies. This paper presents the data of the study where 6-propylthiouracil (6-PTU, 10 ppm) and sodium phenobarbital (NaPB, 1000 ppm) were dosed by feeding from gestational days (GD)6–20, and from GD6 to lactation day 21. The modified CTA detected 6-PTU-induced severe (>70%) suppression of serum THs in dams, with >50% suppressed serum/brain TH levels in offspring and brain heterotopia in postnatal day 21 pups. The modified CTA also detected NaPB-induced mild (<35%) suppression of serum THs in dams, with mild (<35%) reduction of serum/brain TH levels in fetuses but not in pups. These findings suggest that the modified CTA may have a potential as a screening test for offspring THDs.

Preventive effects of a standardized flavonoid extract of safflower in rotenone-induced Parkinson's disease rat model

Parkinson's disease (PD) is a progressive neurodegenerative disorder that occurs after Alzheimer's disease. Rotenone is a neurotoxin commonly used in creating PD models. Safflower (Carthamus tinctorius L.) contains some flavonoids that are effective against neurodegenerative diseases, and it has long been used in the treatment of cerebrovascular diseases in China. In this study, we investigated the preventive effect of safflower standardized flavonoid extract (SAFE) on a rotenone-induced PD rat model. The results showed that SAFE (17.5, 35, or 70 mg kg−1·day−1) treatment modified the progressive loss in body weight, alleviated behavioral deficits, and promoted survival, especially in the middle-dose SAFE (35 mg kg−1·day−1) group. SAFE treatment significantly modifies the progressive decrease in the level of DA and its metabolites, DOPAC and HVA, 5-HT and its metabolite 5-HIAA in the St, and levels of TH-positive DA-ergic neurons in the SNpc. SAFE also inhibited the decrease in TH and DA levels and increase in Ach content in the St. SAFE (35 mg kg−1·day−1) group treatment modifying the rotenone-induced downregulation of JAK2, STAT3, and ɑ7-nAChR, and also modifying the increase in ACh in the hippocampus. SAFE preventive treatment can also partially inhibit changes in the ECS parameters associated with PD. The marker components of SAFE such as Kaempferol 3-O-rutinoside or anhydrosafflor yellow B can bind with TH, JAK2, STAT3, and ɑ7-nAChR based on molecular docking analyses. Current studies have shown that SAFE is a potential candidate for the prevention of PD.

Treating Parkinson's Disease via Activation of BDNF/TrkB Signaling Pathways and Inhibition of Delta-Secretase.

Parkinson's disease (PD) is the second most common neurodegenerative disease with motor disorders as the key clinical features. BDNF/TrkB neurotrophic signalings are progressively reduced, whereas δ-secretase, a protease that cleaves α-synuclein (α-Syn) at N103 and promotes its aggregation and neurotoxicity, is gradually escalated in PD patient brains, associated with dopaminergic neuronal loss in the Substantia Nigra. Here, we show that stimulation of deficient BDNF/TrkB signalings with its small molecular agonist CF3CN displays the promising therapeutic effect, and blockade of δ-secretase with an optimal specific inhibitor #11A exhibits marked therapeutic effect, and combination of both demonstrates additive restorative efficacy in MPTP-induced human SNCA transgenic PD mice. Upon oral administration, CF3CN robustly activates TrkB-mediated neurotrophic pathway in the brains of SNCA mice and decreases α-Syn N103 cleavage by δ-secretase, and #11A strongly blocks δ-secretase and reduces α-Syn N103 fragmentation, increasing TH-positive dopaminergic neurons. The mixture of CF3CN and #11A shows the maximal TH and dopamine levels with demonstrable BDNF as compared to negligible BDNF in vehicle-treated MPTP/SNCA mice, leading to the climaxed motor functions. Notably, both compounds possess the appropriate in vivo PK profiles. Hence, our findings support that CF3CN and #11A are promising therapeutic pharmaceutical agents for treating PD.

Long Non‐coding RNAs Mediate Heart Failure with Preserved Ejection Fraction Associated with Thyroid Dysfunction

IntroductionHeart failure with preserved ejection fraction (HEpEF) carries significantly high morbidity and mortality. HFpEF is associated with preserved contractile function and can present with diastolic dysfunction, cardiac fibrosis and hypothyroidism (low levels of thyroid hormones, THs). We previously demonstrated safe, cardioprotective effects with treatment of active form of THs in multiple rodent models of cardiovascular disorders. Long‐noncoding ribonucleic acids (lncRNAs; &gt;200 nucleotides long) account for large majority of the genome with significant transcriptional potential. However, their role in HFpEF associated with TH dysfunction is unclear. We hypothesized that lncRNAs act as mediators in development of hypothyroid HFpEF.MethodsHearts were isolated from obese ZSF1 rats that presented with HFpEF phenotype. Wild type and ZSF1 lean rats served as controls. Cardiac ultrasound and morphometric analyses were performed. RNA was isolated from left ventricular (LV) tissues and studied using Agilent LncRNA Microarray platform and analyzed using Feature Extraction and GeneSpring. Fibroblasts were isolated from wild type adult rat hearts and treated with TH receptor inhibitor. Real‐time quantitative polymerase chain reaction was used to study lncRNA expression.ResultsStudies revealed that total thyroxine TH levels significantly decreased in five‐six‐month old (early; p&lt;0.05) ZSF1 obese rats compared to ZSF1 lean controls (45% decrease) and wild type controls (42% decrease), and this remained low at 13 months (late; p&lt;0.05). Total tri‐iodothyronine TH levels also followed similar pattern in the early time‐point (37%‐42% decrease). ZSF1 obese rats showed increased normalized heart weight, LV weight and liver weight indicating cardiac hypertrophy and development of HF. In early obese rats, echocardiography showed preserved LV EF and significantly elevated E/E’ indicating diastolic dysfunction (p&lt;0.05). LncRNA Microarray analysis including unsupervised hierarchical clustering showed that several unique lncRNAs were significantly altered (p&lt;0.05; &gt;2‐fold change) in obese LVs compared to the lean or wild type control counterparts and select lncRNA expression was validated with qPCR. Furthermore, isolated wild type adult rat cardiac fibroblasts subjected to TH receptor inhibition (mimicking hypothyroidism) in vitro showed significant increase in lncRNA expression that was also increased in obese ZSF1 hearts presenting with hypothyroidism (p&lt;0.05).ConclusionsThese results indicate that lncRNAs may play important roles in in HFpEF pathogenesis associated with hypothyroidism. These studies will serve as significant step in identification of key lncRNAs in cardiac‐thyroid axis offering potentially valuable translational opportunities.

PHYSICO–CHEMICAL ANALYSIS OF WATER SAMPLES COLLECTED FROM THE SELECTED STUDY AREAS OF RANIPET DISTRICT, TAMIL NADU, INDIA

Various organic and inorganic pollutants present in the industrial effluents released into the aquatic ecosystem. This pollutant is harmful to the aquatic biota and also leads to the bioaccumulation in the terrestrial biota. Five different sampling sites (S1-S5) are selected for this study. The physico-chemical parameters such as pH, temperature, turbidity, electrical conductivity, total hardness, total dissolved solids, calcium, magnesium, sulphate, ammonia, nitrite, nitrate, chloride, biochemical oxygen demand and chemical oxygen demand of the water samples are analyzed by standard protocols and the data are interpreted by student t test and ANOVA. Results evidenced the significantly varied physico-chemical parameters, especially TH and TDS levels were beyond the permissible limit.

Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state.

Idiopathic Parkinson’s disease is characterized by a progressive loss of dopaminergic neurons, but the exact disease aetiology remains largely unknown. To date, Parkinson’s disease research has mainly focused on nigral dopaminergic neurons, although recent studies suggest disease-related changes also in non-neuronal cells and in midbrain regions beyond the substantia nigra. While there is some evidence for glial involvement in Parkinson’s disease, the molecular mechanisms remain poorly understood. The aim of this study was to characterize the contribution of all cell types of the midbrain to Parkinson’s disease pathology by single-nuclei RNA sequencing and to assess the cell type-specific risk for Parkinson’s disease using the latest genome-wide association study.We profiled >41 000 single-nuclei transcriptomes of post-mortem midbrain from six idiopathic Parkinson’s disease patients and five age-/sex-matched controls. To validate our findings in a spatial context, we utilized immunolabelling of the same tissues. Moreover, we analysed Parkinson’s disease-associated risk enrichment in genes with cell type-specific expression patterns. We discovered a neuronal cell cluster characterized by CADPS2 overexpression and low TH levels, which was exclusively present in idiopathic Parkinson’s disease midbrains. Validation analyses in laser-microdissected neurons suggest that this cluster represents dysfunctional dopaminergic neurons. With regard to glial cells, we observed an increase in nigral microglia in Parkinson’s disease patients. Moreover, nigral idiopathic Parkinson’s disease microglia were more amoeboid, indicating an activated state. We also discovered a reduction in idiopathic Parkinson’s disease oligodendrocyte numbers with the remaining cells being characterized by a stress-induced upregulation of S100B. Parkinson’s disease risk variants were associated with glia- and neuron-specific gene expression patterns in idiopathic Parkinson’s disease cases. Furthermore, astrocytes and microglia presented idiopathic Parkinson’s disease-specific cell proliferation and dysregulation of genes related to unfolded protein response and cytokine signalling. While reactive patient astrocytes showed CD44 overexpression, idiopathic Parkinson’s disease microglia revealed a pro-inflammatory trajectory characterized by elevated levels of IL1B, GPNMB and HSP90AA1.Taken together, we generated the first single-nuclei RNA sequencing dataset from the idiopathic Parkinson’s disease midbrain, which highlights a disease-specific neuronal cell cluster as well as ‘pan-glial’ activation as a central mechanism in the pathology of the movement disorder. This finding warrants further research into inflammatory signalling and immunomodulatory treatments in Parkinson’s disease.

Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels

ObjectiveThyroid hormones (TH) are essential for the homeostatic control of energy metabolism and the regulation of body temperature. The hypothalamic–pituitary–thyroid (HPT) axis is regulated by negative feedback mechanisms, ensuring that TH levels are maintained at a constant level. However, the feedback mechanisms underlying the resetting of the HPT axis regulation in the control of body temperature are still not fully understood. Here, we aimed to determine the thermoregulatory response in hypothyroid mice to different environmental temperatures and the underlying mechanisms. MethodsDistinct thermogenic challenges were induced in hypothyroid female C57BL/6N and leptin-deficient ob/ob mice through housing at either room temperature or thermoneutrality. The thermogenic and metabolic effects were analyzed through metabolic chambers, 18F-FDG-PET/MRI, infrared thermography, metabolic profiling, histology, gene expression and Western blot analysis. ResultsIn hypothyroid mice maintained at room temperature, high leptin serum levels induce a pyrexic effect leading to the stabilization of body temperature through brown adipose tissue thermogenesis and white adipose tissue browning. Housing at thermoneutrality leads to the normalization of leptin levels and a reduction of the central temperature set point, resulting in decreased thermogenesis in brown and white adipose tissue and skeletal muscle and a significant decline in body temperature. Furthermore, anapyrexia in hypothyroid leptin-deficient ob/ob mice indicates that besides its pyrexic actions, leptin exerts a stimulatory effect on the HPT axis to stabilize the remaining TH serum levels in hypothyroid mice. ConclusionThis study led to the identification of a previously unknown endocrine loop in which leptin acts in concert with the HPT axis to stabilize body temperature in hypothyroid mice.

Geochemical Analysis of Groundwater for Drinking, Irrigation, and Human Health Impacts in Uddanam Area of Srikakulam District of Andhra Pradesh, India

The current study's goal is to discover the geochemical analysis of groundwater in the uddanam area of the Srikakulam district of Andhra Pradesh, India. In the current study area, 50 groundwater samples were collected and analyzed for physicochemical properties such as cations, anions, total hardness, conductivity, and alkalinity. This was assessed for its suitability for drinking and irrigation purposes by calculating pH, EC, TDS, hardness, and alkalinity in addition to major cations (Na+, K+, Ca2+, Mg2+) and anions (HCO3-, Cl-, SO42-, NO32-, F-). Chemical indices such as SAR, percent Na, permeability index, RSC, Kelly's Ratio, Magnesium Ratio, and Non-carbonate hardness (NCH) have been calculated based on the analytical results. Water with high alkalinity may be aesthetically unfit for drinking, whereas water with high TDS and TH may not be recommended for consumption by people suffering from kidney and related diseases. Geogenic, anthropogenic influence, agricultural activity, and mineral dissolution, Presence of high TDS and TH levels were the primary causes for chronic kidney disease (CKD), not suitable for drinking and irrigation purposes.

Rapid immunohistological measurement of tyrosine hydroxylase in rat midbrain by near-infrared instrument-based detection

We present a robust, fresh-frozen approach to immunohistochemistry (IHC), without committing the tissue to IHC via fixation and cryopreservation while maintaining long-term storage, using LiCor-based infrared (IR) quantification for sensitive assessment of TH in immunoreacted midbrain sections for quantitative comparison across studies. In fresh-frozen tissue stored up to 1 year prior to IHC reaction, we found our method to be highly sensitive to rotenone treatment in 3-month-old Sprague-Dawley rats, and correlated with a significant decline in rotarod latency-to-fall measurement by approximately 2.5 fold. The measured midbrain region revealed a 31 % lower TH signal when compared to control (p < 0.01 by t test, n = 5). Bivariate analysis of integrated TH counts versus rotarod latency-to-fall indicates a positive slope and modest but significant correlation of R2 = 0.68 (p < 0.05, n = 10). These results indicate this rapid, instrument-based quantification method by IR detection successfully quantifies TH levels in rat brain tissue, while taking only 5 days from euthanasia to data output. This approach also allows for the identification of multiple targets by IHC with the simultaneous performance of downstream molecular analysis within the same animal tissue, allowing for the use of fewer animals per study.

Analysis of Hypothalamic TRH Neurons in Regulating Thyroid Hormone Levels

Thyroid hormone (TH) is a major regulator of development and metabolism. An important mechanism controlling TH production is the negative feedback at the hypothalamic and pituitary level and it has been suggested that thyroid hormone receptor β (TRβ) is the main mediator of TH actions in the hypothalamic paraventricular nucleus (PVN). Nevertheless, the direct actions of TH and TRβ in the negative regulation of TRH have yet to be demonstrated in vivo. Here we used two approaches to investigate the TRH neuron. First, we used a chemogenetic tool to directly investigate the role of TRH neurons on the regulation of thyroid hormone levels. Mice expressing Cre-recombinase in TRH neurons received bilateral injections of the activating designer receptors exclusively activated by designer drugs (DREADD) directly into the PVN. Activation of TRH neurons produced a rapid and sustained increase in circulating TSH levels in both males and females. TSH levels increased approximately 10-fold from baseline within 15 minutes of injection of CNO, returning to baseline within 2.5 hours. TH levels were increased approximately 2-fold in males and females. Therefore, using a chemogenetic approach, we were able to directly evaluated the role of PVN TRH neurons on the control of thyroid activity, for the first time. Next, we generated mice deficient in TRβ specifically in neurons expressing melanocortin 4 receptor (MC4R), which overlaps with TRH expression in the PVN. Knockout mice (KO) developed normally and showed no change in TH and TSH levels. TRH mRNA levels in the PVN of KO mice were similar to control mice. To investigate if the deletion of TRβ in the PVN changes the sensitivity of the HPT axis to T3, mice were rendered hypothyroid and given increasing doses of T3 for 2 weeks. Results show no difference in TRH mRNA or serum TSH between controls and KO. Surprisingly, despite the presence of detectable genomic recombination on the TRβ gene in the PVN, there was no difference in TRβ mRNA expression between control and KO mice, suggesting that either MC4R-positive neurons do not express TRβ or they represent a very small population of TRβ-positive cells in the PVN. Present data show that TRH neuron activation rapidly stimulates TSH release and increases TH levels, demonstrating a major role of these neurons in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis. Nevertheless, deletion of TRβ from MC4R neurons had no major effect on either TRH or TH levels in in mice. Additionally, TRβ in MC4R-positive TRH neurons in the PVN is not necessary for TH-induced suppression of TRH mRNA. Although further studies are necessary, these data suggest that there are distinct populations of hypophysiotropic TRH neurons in the PVN, some of which are not regulated by thyroid hormone and TRβ.

IPSC-Derived Human Hepatocytes as a Novel Model to Investigate Thyroid Hormone Action and Signaling

Thyroid hormone (TH) actions are essential to normal metabolism and neurologic function. Abnormal TH levels can lead to significant morbidity including metabolic abnormalities, cardiac disease, and obesity. TH action is mediated by the thyroid hormone receptor (TR) isoforms and their coregulators. In the disease models of Resistance to Thyroid Hormone (RTH) it is clear that the TR isoforms play tissue-specific roles in humans, however a platform for drug discovery to potentially treat the diseases does not exist. We hypothesize that human hepatocytes (iHeps) derived from induced pluripotent stem cells (iPSCs) will serve as an ideal model to study TH signaling and to delineate mechanisms of TH diseases in humans. To investigate the TH action in humans, we have developed a serum free human iPSC hepatic differentiation protocol that utilizes sequential exposure to growth factors to mimic actual human development. iHeps are robustly responsive to TH with over 1000 regulated genes. Importantly, they allow us to use CRISPR/Cas9 to determine molecular physiology and mechanism of disease. To demonstrate the role of TRs in TH signaling in human liver cells we have focused on TRβ1 the main TR isoform expressed in liver. we knocked out TRβ1 (THRBKO) using guide RNAs (gRNAs) we engineered to specific genomic loci to truncate the expression of this isoform at the DNA binding domain. Also, to define mechanisms of TR action in the context of RTH, we used this same approach to introduce the Δ337T mutation found in human TRβ1 that causes RTH. Both THRBKO and Δ337T lines are karyotypically normal and flow cytometry analysis in both lines demonstrated that these lines differentiated normally into hepatocytes after gene editing with CRISPR/Cas9. Once clones were identified the edited iHeps were treated with PBS (vehicle) or T3 (10nM) for 24 hours. Real-time quantitative PCR (RT qPCR) was done to assess mRNA expression of T3 target genes. RT qPCR analysis confirmed the success of TRβ1 deletion as the response to T3 was lost on both positive and negative THRB targets. In the Δ337T iHeps, the response to TH was diminshed indicating the successful generation of this line. These preliminary results confirm our ability to edit IPSCs and then to differentiate into hepatocytes, allowing us to further study the action of TH and the mutations involved in RTH.