Blood Thyroxine Research Articles

Effects of Transport Duration and Pre-Transport Fasting on Blood Biochemistry in Dorper × Mongolian Sheep.

Transport is a high-risk time for sheep, especially if the distances are long and sheep are fasted for a long time beforehand. Two experiments were conducted to compare transport durations of 1 hour (1 h) and 3 hours (3 h) and the effects of feeding before transport using Dorper × Mongolian sheep, which are typical of the region and may be tolerant of the high temperatures in the Inner Mongolian summer. Thirty 4-month-old male sheep were randomly divided into two treatment groups, with 15 sheep/treatment in each experiment, to evaluate the effects on blood biochemical indicators, stress hormone levels, rectal temperatures, and antioxidant status of lambs in summer. In Experiment 1, the levels of triglycerides and free fatty acids after 3 h transport were significantly lower than after 1 h transport (p < 0.05). The levels of thyroxine and malondialdehyde in blood were greater after 3 h transport than 1 h transport (p < 0.05). Creatine kinase levels after 3 h transport tended to be lower than after 1 h transport (p = 0.051). In Experiment 2, the levels of urea and superoxide dismutase in the group fasted pre-transport was significantly lower than those of the group fed pre-transport (p < 0.05). The serum cortisol level in the pre-transport fed group was higher compared to the group fed pre-transport (p = 0.04). Total antioxidant capacity in the pre-transport fasted group tended to be lower compared to that in the pre-transport fed group (p < 0.0001). We conclude that the reduction in nutritional status of sheep transported for longer and without feed pre-transport suggests that transporting sheep in hot conditions in northern China after fasting for a long period should be restricted. However, a decrease in the stress induced by transport following fasting is worthy of further study.

3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity.

Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations are known to destabilise the TTR tetramer, leading to its extracellular pathological aggregation accumulating in several organs, such as heart, peripheral and autonomic nerves, and leptomeninges. Tolcapone is an FDA-approved drug for Parkinson's disease that has been repurposed as a TTR stabiliser. We characterised 3-O-methyltolcapone and two newly synthesized lipophilic analogues, which are expected to be protected from the metabolic glucuronidation that is responsible for the lability of tolcapone in the organism. Immunoblotting assays indicated the high degree of TTR stabilisation, coupled with binding selectivity towards TTR in diluted plasma of 3-O-methyltolcapone and its lipophilic analogues. Furthermore, in vitro toxicity data showed their several-fold improved neuronal and hepatic safety compared to tolcapone. Calorimetric and structural data showed that both T4 binding sites of TTR are occupied by 3-O-methyltolcapone and its lipophilic analogs, consistent with an effective TTR tetramer stabilisation. Moreover, in vitro permeability studies showed that the three compounds can effectively cross the blood-brain barrier, which is a prerequisite for the inhibition of TTR amyloidogenesis in the cerebrospinal fluid. Our data demonstrate the relevance of 3-O-methyltolcapone and its lipophilic analogs as potent inhibitors of TTR amyloidogenesis.

Selenium regulates T cell differentiation in experimental autoimmune thyroiditis in mice

Selenium (Se) is an essential trace element that plays an important role in thyroid physiology. Se supplementation can reduce levels of autoimmune thyroid antibodies, which may be beneficial in Hashimoto's thyroiditis (HT). However, the long-term benefits of Se supplementation for HT patients are controversial and there is no clear clinical evidence to support it, so further basic and clinical research is needed. The effect of Se on immune cells, especially T cells, in autoimmune thyroiditis (AIT) has not been elucidated. Here, we replicated a mouse model of experimental autoimmune thyroiditis (EAT) on a high-iodine diet and treated it with Se supplementation. At week 8 of the experiment, Se supplementation reduced the destruction of thyroid follicles and the infiltration rate of lymphocytes in EAT mice, and reversed the disturbance of peripheral blood thyroxine and thyroid autoantibody levels. Further examination revealed that Se had broad effects on T-cell subsets. Its effects include reducing the production of pro-inflammatory cytokines by Th1 cells, inhibiting the differentiation and production of cytokines by Th2 and Th17 cells, and upregulating the differentiation and production of cytokines by Treg cells. These changes help alleviate thyroid follicle damage during EAT. In conclusion, selenium supplementation has the potential to improve the prognosis of AIT by altering the subset differentiation and/or function of CD4+ T cells.

Heat tolerance in Mashona beef cows in semi-arid rangelands: does conformation matter?

High temperatures and frequent heat waves raise concerns about heat stress in cattle in grass-based systems, especially in arid and semiarid areas. This study analysed the relationship between conformation traits and physiological parameters associated with heat stress in Mashona cattle. A total of 200 records from fifty cows were used to study the relationships between seven conformation traits and physiological parameters associated with heat stress. Body conformation traits were categorised into three principal components related to body capacity (body depth, flank circumference, chest girth), frame size (stature and body length), and loose skin fold (navel height and dewlap size). As the size of abdominopelvic and thoracic cavities increased, respiratory rate, heart rate, and rectal temperature decreased significantly, while blood triiodothyronine concentration increased. Cattle with deeper bodies, larger flanks, and larger chest girths had significantly lower heart rate, respiratory rate, and rectal temperature but higher blood triiodothyronine concentration than cattle with shallower bodies, smaller flanks, and smaller chest girths. Respiratory rate increased with increasing frame size. Large-framed cattle had significantly higher respiratory rate and lower blood thyroxine concentration. Small-framed cattle with larger chest girth, larger dewlap, and navel farther from the ground surface are better adapted to higher ambient temperatures.

The Toxicity and Antibacterial Effects of Povidone-Iodine Irrigation in Fracture Surgery.

ObjectiveSurgical site infection is a common complication of surgery, especially in orthopedics. Povidone‐Iodine (PI) is one of the oldest and most commonly used disinfectants in surgery. However, the toxicity and antimicrobial effect of PI have not been discussed. In addition, no study has explored the optimum PI concentration for sterilization and tissue healing. This study explores the germicidal efficacy of different concentrations PI, in addition, the toxicity and antibacterial effects of PI irrigation in fracture surgery are also discussed.MethodsMethicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa (P. aeruginosa) were used to evaluate the germicidal efficacy of PI in vitro and in vivo. In vitro, the effects of PI on bacterial growth were analyzed. 2.5%, 1.25%, 0.5%, 0.25%, 0.05%, 0.025%, 0.005%, 0.0025% and 0% PI was added into the bacterial suspension, besides, the bacterial algebra and growth rate were tested. Meanwhile, the fluorescence intensity of viable bacteria was also tested to evaluate the effects of PI on bacterial survival. In vivo, first, femoral fracture with wound infection rat models were established. Second, thyroid gland sections, blood thyroxine, urinary iodine, wound local skin, muscle and bone tissue sections, serum creatinine and alanine aminotransferase, serum and bone local tissue interleukin‐6 (IL‐6), interleukin‐10 (IL‐10), bone morphogenetic protein (BMP‐2), vascular endothelial growth factor (VEGF) and transforming growth factor (TGF‐β1) were detected in rat femoral shaft fracture model with 5%, 2.5%, 0.5%, 0.05%, and 0% PI irrigation. Third, tissue bacteria culture was tested in rat femoral fracture with wound infection model with different concentrations PI irrigation.Results In vitro, 2.5%, 1.25%, 0.5% PI inhibited the growth of bacteria. 1.25%, 0.5% PI killed all the bacteria, while 0.25%, 0.05% PI had not killed bacteria after about 10 min. The iodine absorption of 5%, 2.5%, 0.5% PI irrigation did not cause thyroid injury. The 5%, 2.5%, 0.5% PI irrigation did not make serum creatinine and alanine aminotransferase abnormal and can remove bacteria from wounds. The 0.5%, 2.5% PI irrigation can promote tissue healing and increase BMP‐2, VEGF, TGF‐β1, IL‐10, in addition, decrease IL‐6. 5% PI irrigation would inhibit tissue healing, and increase IL‐6, decrease BMP‐2, VEGF, TGF‐β1, IL‐10.ConclusionsPovidone‐Iodine was a widely used disinfectant and 2.5%, 1.25% and 0.5% PI could effectively kill bacteria. Five percent and lower concentration PI irrigation was safe and could not cause thyroid, kidney and liver damage. The 0.5% PI irrigation was beneficial for tissue healing but 5% PI irrigation was the opposite.

Relationship of thyroid gland elasticity with age, gender and thyroid gland volume in the shear-wave ultrasound elastography

Objectives: The aim of the study is to determine the correlation between thyroid gland elasticity with thyroxine, thyroid-stimulating hormone levels, age, gender and thyroid gland volume in the normal population. Methods: The study was conducted with 105 healthy cases. Thyroid gland elasticity was evaluated in axial plan using ultrasonography. Results: The relationship between thyroid gland elasticity and thyroxine, thyroid-stimulating hormone levels, age, gender and thyroid gland volume was evaluated. The mean thyroid gland volume was 11.95 ± 9.23 mm3. A moderate negative correlation was found between thyroid gland volume and kPa value observed from the elastography examination. A moderate negative correlation was found between elastography kPa value and blood thyroxine level. No correlations were found between thyroid-stimulating hormone level, age, gender and thyroid gland elasticity. Conclusions: The negative correlation between thyroid gland volume and thyroxine level with thyroid gland elasticity should be considered in elastographic evaluations.

Maternal hypothyroidism prolongs gestation period and impairs glucose tolerance in offspring of Wistar rats.

Pregnancy is a critical period keenly regulated by both maternal and foetal factors and a shift in these factors could result in severe complications manifesting in foetal and adult life. However, maternal hypothyroidism before and/or during pregnancy is a critical factor. This study investigated the effect of maternal hypothyroidism on glucose tolerance and thyroid function in male and female offspring. Fifteen adult female Wistar rats were divided intothree groups: Group 1 (sham-control), Group 2 (thyrodectomized) and Group 3 (thyroidectomised+L-thyroxine treated). Blood thyroxine (T4) level was measured on the day 10 after thyroidectomy in Groups 1 and 2, and day 35 inGroup 3. Males were introduced to the female rats after T4measurement. At PND-112, T4 levels of their offspring were measured. Oral Glucose Tolerance Test (OGTT) was measured in offspring at PND-133. Thyroxine reduced significantly in Group 2 and their offspring (male and female) compared to Group 3 while gestation period was prolonged significantly in Group 2 compared to Group 1. Hypothyroid male offspring showed depressed glucose tolerance, however, no effect was observed in female offspring. This study suggests that maternal hypothyroidism prolonged gestation period, induced foetal hypothyroidism in both genders and depressed glucose tolerance in male offspring.

PetSavers research

Tim Williams and Nick Bexfield received BSAVA PetSavers funding for the student research project (SRP) entitled A study to determine the effects of time and storage conditions on the stability of total serum thyroxine in feline blood. Student Rory Scrace describes the project and its findings.

Oral transmucosal absorption of iodine after intraoral preparation with povidone-iodine prior to oral surgeries: a randomized controlled study in 12 male patients.

Absorption of iodine through skin and an increased incidence of thyroid disorders due to iodophor exposure are reported. However, the risk of oral transmucosal absorption of povidone-iodine after intraoral preparation is not clear. To investigate the possibility of oral transmucosal absorption of povidone-iodine after intraoral preparation and its effect on thyroxine level in blood. A randomized controlled study was carried out in the department of oral and maxillofacial surgery. Twenty- to 40-year-old healthy male adults planning to receive oral surgery under general anesthesia were enrolled. The study group received povidone-iodine irrigation of oral cavity for 3min as intraoral preparation before operation. The control group received chlorhexidine gluconate irrigation of oral cavity for 3min as intraoral preparation before operation. Iodine levels in blood and urine, and thyroxine levels in blood were tested and compared, before and after operation. In total, 24 patients were included and analyzed finally. We found that after intraoral preparation with povidone-iodine, serum iodine level increased significantly to 2-3 times the pre-operation level in 15-30min, and the urinary iodine level increased to 5 times the pre-operation level on the first day after operation. Iodine levels in blood and urine decreased significantly on the third day after operation but still significantly greater than the pre-operation levels. However, thyroxine levels were not altered accordingly. Oral transmucosal absorption of iodine is observed when povidone-iodine is used for intraoral preparation in healthy male adults, though the free thyroxine in blood is not affected accordingly. Povidone-iodine is commonly used as an antiseptic in oral surgery and dental clinics. Based on our findings that iodine levels in blood and urine may elevate significantly after intraoral preparation with povidone-iodine prior to oral surgeries, care must be taken for individuals when excess iodine intakes can endanger the safety of the patient. Name of the trial registry: The Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ). Registration number: ChiCTR2100042028.

Lithium from breast-milk inhibits thyroid iodine uptake and hormone production, which are remedied by maternal iodine supplementation.

Lithium is especially taken as a maintenance medication for Bipolar Disorder. In women with bipolar disorder, lithium is often effective during postpartum period, but breast-feeding for medicated mothers is controversial because of harmful effects for her child. At present, the biological mechanisms of lithium are not well-understood, affecting its usage and overall health implications. We developed a rat lithium and breast-feeding model at human therapeutic levels to study the effects of lithium exposure through breast-milk on pups' thyroid function. Novel laser analytical spectroscopy, along with traditional blood and immunohistochemical tests, were applied to further investigate the mechanisms behind the thyroid dysfunction. Maternal iodine supplementation was evaluated as a therapeutic method to address the pups' thyroid dysfunction. Pups exposed to lithium via breastmilk, even with the dam on a sub-therapeutic level, experienced weight gain, reduced blood thyroxine (T4 ), and elevated blood urea nitrogen, indicating effects on thyroid and kidney function. We show that lithium inhibited iodine uptake by thyroid follicles, initiating a mechanism that reduced iodination of tyrosine, thyroglobulin cleavage, and thyroid hormone production. Importantly, infant thyroid function can be significantly improved by administering supplementary iodine to the medicated dam's diet during breast-feeding. These results elucidate the mechanisms of lithium in thyroid function, provide valuable information on use postpartum, and suggest a clinically applicable remedy to side-effects. The results are particularly important for patients (and their infants) who respond well to lithium and need, or choose, to breast-feed.

Cerium oxide nanoparticles and metformin increase the reliability of the prooxidant/antioxidant balance and the survival of ageing rats

In comparison with the action of metformin — mimetic of the calorie restricted diet, which prolong the animals lifespan, it has been studied the effect of nanoparticles of cerium dioxide (CeO2 NPs (1-2 nm)) on survival, physiological indices (the concentration of thyroxine, rectal temperature), as well as biochemical indices (content of lipid hydroperoxides, aconitase, glutathione peroxidase, glutaredoxin, glutathione reductase, NADP+ -dehydrogenase activities (glucose-6-phosphate-, malate- and isocitrate dehydrogenase)) in serum, liver mitochondrial and postmitochondrial fraction of ageing rats. It has been found that the prolonged use of CeO2 NPs with drinking water (0.25-0.30 mg/kg of body weight per day) and metformin (100-110 mg/kg of body weight per day) from 670 days after the birth lead to a significant increase in survival (the median survival of control rats was 900, in animals treated with CeO2 NPs — 960, and metformin — 990 days), a decrease in rectal temperature, a slowdown in the decrease in the level of thyroxine in blood, and normalization of the prooxidant/antioxidant balance in liver and blood tissues. Calculated integral index of reliability of prooxidant-antioxidant balance (reliability coefficient) in the studied tissues of rats in response to the application of the CeO2 NPs increased 4.99 times, and metformin — 4.94 times compared to intact animals. The data obtained allow us concluding about the prospects of the CeO2 NPs, as well as metformin for the development of geroprotector drugs, increasing the healthspan and survival of an ageing organism.

The inhibition of cellular toxicity of amyloid-β by dissociated transthyretin

The protective effect of transthyretin (TTR) on cellular toxicity of β-amyloid (Aβ) has been previously reported. TTR is a tetrameric carrier of thyroxine in blood and cerebrospinal fluid, the pathogenic aggregation of which causes systemic amyloidosis. However, studies have documented a protective effect of TTR against cellular toxicity of pathogenic Aβ, a protein associated with Alzheimer's disease. TTR binds Aβ, alters its aggregation, and inhibits its toxicity both in vitro and in vivo In this study, we investigate whether the amyloidogenic ability of TTR and its antiamyloid inhibitory effect are associated. Using protein aggregation and cytotoxicity assays, we found that the dissociation of the TTR tetramer, required for its amyloid pathogenesis, is also necessary to prevent cellular toxicity from Aβ oligomers. These findings suggest that the Aβ-binding site of TTR may be hidden in its tetrameric form. Aided by computational docking and peptide screening, we identified a TTR segment that is capable of altering Aβ aggregation and toxicity, mimicking TTR cellular protection. EM, immune detection analysis, and assessment of aggregation and cytotoxicity revealed that the TTR segment inhibits Aβ oligomer formation and also promotes the formation of nontoxic, nonamyloid amorphous aggregates, which are more sensitive to protease digestion. Finally, this segment also inhibits seeding of Aβ catalyzed by Aβ fibrils extracted from the brain of an Alzheimer's patient. Together, these findings suggest that mimicking the inhibitory effect of TTR with peptide-based therapeutics represents an additional avenue to explore for the treatment of Alzheimer's disease.

Interactions of tolcapone analogues as stabilizers of the amyloidogenic protein transthyretin

Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine and retinol in blood and cerebrospinal fluid. TTR stabilizers, such as tolcapone, an FDA approved drug for Parkinson’s disease, are able to interact with residues of the thyroxine-binding sites of TTR, both wild type and pathogenic mutant forms, thereby stabilizing its tetrameric native state and inhibiting amyloidogenesis. Herein, we report on the synthesis of 3-deoxytolcapone, a novel stabilizer of TTR. The high-resolution X-ray analyses of the interactions of 3-O-methyltolcapone and 3-deoxytolcapone with TTR were performed. In the two TTR−ligand complexes the tolcapone analogues establish mainly H-bond and hydrophobic interactions with residues of the thyroxine-binding site of the TTR tetramer. Both compounds are capable of high and selective stabilization of TTR in the presence of plasma proteins, despite their markedly different ‘forward’ and ‘reverse’ binding mode, respectively. In fact, the loss or the weakening of stabilizing interactions with protein residues of 3-deoxytolcapone in comparison with tolcapone and 3-O-methyltolcapone is compensated by new interactions established at the dimer-dimer interface. Our data, coupled with previously reported data on the pharmacokinetics properties in humans of tolcapone and 3-O-methyltolcapone, further support the relevance of the latter tolcapone analogue as TTR stabilizer.

Endocrine disruption: Molecular interactions of environmental bisphenol contaminants with thyroid hormone receptor and thyroxine-binding globulin.

Many bisphenol A (BPA) analogs have been commercially used recently, such as 2,2-bis(4-hydroxyphenyl)butane (BPB), 4,4'-ethylidenebisphenol, 4,4'-methylenediphenol (BPF), 4,4'-(1,4-phenylenediisopropylidene)bisphenol (BPP), 4,4'-dihydroxydiphenyl sulfone (BPS), 4,4'-cyclohexylidenebisphenol (BPZ), 4,4'-(hexafluoroisopropylidene)diphenol (BPAF), 4,4'-(1-phenylethylidene)bisphenol (BPAP), and 2,2-bis(4-hydroxy-3,5-dimethylphenyl)propane (TMBPA), to circumvent adverse effects of BPA. However, their increasing use is also contaminating the environment, which is a potential cause of concern for human health. Thyroid hormone transport and signaling are potential targets for endocrine-disrupting activity of BPA analogs. Thyroxine-binding globulin (TBG) is the major carrier protein for thyroxine (T4) and triiodothyronine (T3) in blood. Thyroid hormones exert their action through thyroid hormone receptors (TRα and TRβ). This report presents the thyroid-disrupting potential of indicated nine BPA analogs from structure-based studies with TBG and TRα. Each BPA analog formed important polar and hydrophobic interactions with a number of residues of TBG and TRα. Majority of TBG residues (77-100%) and TRα residues (70-91%) interacting with BPA analogs were common with those of native ligands T4 and T3, respectively. Majority of BPA analogs interacted with TBG forming a salt bridge interaction at Lys-270. The hydrogen-bonding interaction of T3 with TRα at His-381 was also shared by majority of analogs. The binding energy for BPP, BPB, BPZ, BPAP, and TMBPA with both proteins was closer to binding energy of respective native ligands. The similarity in structural binding characteristics suggested potential disrupting activity of thyroid hormone signaling and transport.

New Thieno-[2,3-d]pyrimidine-Based Functional Antagonist for the Receptor of Thyroid Stimulating Hormone.

Thyroid stimulating hormone (TSH) receptor antagonists are required for the treatment of TSH-dependent tumors and Graves disease. We developed the compound 5-amino-N-(tert-butyl)-4-(4-iodophenyl)-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxamide (TP48) and showed that it reduces the TSH-stimulated adenylate cyclase activity in rat thyroid membranes. Pretreatment of rats with compound TP48 (ip, 40 mg/kg) reduced the increase in the levels of total and free thyroxin in blood and the increase in the expression of thyroglobulin and D2 deiodinase genes in the thyroid gland, which are responsible for the synthesis of thyroid hormones, which were caused by intranasal administration of thyroliberin to animals (300μg/kg). These data indicate that compound TP48 is a functional antagonist of the TSH receptor and can be used to correct the thyroid status in hyperthyroidism.

Diffusive non-toxic goiter and purbatic course in girls

Objective of the study. To study the peculiarities of the puberty course in girls with diffuse non-toxic goiter (DNG) and justify an individual approach to prevention of its disorders.Materials and methods. Compares the features of the puberty course and state of the thyroid system in girls with DNG (main group), which was first diagnosed at 9–13 years in the prepubertal period (n = 51) and early puberty (n = 58). The comparison group consisted of 107 peers with a normal thyroid volume, harmonious physical development and physiological course of puberty. An ultrasound of the thyroid gland was performed; thyroid stimulating hormone (TSH) value, free fractions of thyroxine (fT4) and free triiodothyronine (fT3) in blood were determined, TSH/fT4 ratios and fT3/fT4 ratios were calculated in conventional units. Sexual development and puberty course were also studied.Results. An individual analysis of sexual development during the initial examination allowed us to determine its normal character in 90.0% girls with disabilities, 6.4% recorded an acceleration of its pace for 1–2 years, and only 2 girls (1.8%) 13 years old were diagnosed with a slowdown pace of puberty. Two (1.8%) 10-year old girls had inverted puberty. It was found that an earlier onset of puberty occurs with an increase in TSH and fT3 levels against the background of normal fT4. Dynamics of observation showed an increase of patients with signs of thyroid failure, which was accompanied by a delay in sexual development in 11.1% and menstrual dysfunction in 28.0% girls.Conclusion. Girls with DNG identified in pre- and early puberty increase the risk of delayed sexual development and menstrual dysfunction, which is the rationale for therapy aimed at correcting and preventing the progression of thyroid dysfunction. The feasibility of using potassium iodide and/or L-thyroxine in order to prevent violations of the puberty course in girls with DNG is substantiated

Functional condition of the thyroid gland of newborns from methers with a diffuse toxic goiter

Objective: to study the functional state of the thyroid gland in newborns from mothers with diffuse toxic goiter, depending on the level of antibodies to thyroid stimulating hormone receptors (AB-rTSH).Materials and methods: 68 newborns from 67 mothers with diffuse toxic goiter were examined. The control group included 49 newborns from 49 mothers without thyroid pathology. To assess the functional state of the thyroid gland of newborns, we determined the levels of thyroid stimulating hormone, free thyroxine (fT4), and AB-rTSH in cord blood and calculated the TSH/fT4 coefficient, which allows us to differentiate congenital hypothyroidism from neonatal thyrotoxicosis. On the 4-7th day of life, all newborns underwent ultrasound examination (ultrasound) of the thyroid gland.Results: newborns from mothers with diffuse toxic goiter had lower growth-weight indices in comparison with the same indices of the control group and they often showed thyroid hyperplasia. It was shown that the increased content of AB-rTSH in the blood serum of pregnant women with diffuse toxic goiter and in the umbilical cord blood of newborns can contribute to the development of neonatal thyrotoxicosis, detected in 16.2 % of newborns.Conclusions: increased levels of AB-rTSH in the blood serum of mothers with DTG, especially in the second half of pregnancy, and in the umbilical cord blood of newborns affect the formation of thyroid hyperplasia in newborns and contribute to the development of neonatal thyrotoxicosis.

Low levels of free thyroxine in umbilical cord blood is associated with a reduce in deiodinase 2 activity in human trophoblast from gestational diabetes pregnancies

Low levels of free thyroxine in umbilical cord blood is associated with a reduce in deiodinase 2 activity in human trophoblast from gestational diabetes pregnancies

Relationship between peripheral blood thyroxine levels and cardiac function in patients with chronic heart failure

Objective To investigate the relationship between peripheral blood thyroxine levels and cardiac function in elderly patients with chronic heart failure. Methods Seventy patients with chronic heart failure admitted into our hospital from January 2016 to December 2017 were enrolled as the study group, and 70 healthy subjects were collected as the control group. Left ventricular ejection fraction(LVEF)and serum thyroxine levels were measured in both groups. Results LVEF, serum levels of total triiodothyronine(TT3)and total thyroxine(TT4)were lower in the study group than in the control group[(37.3±2.4)% vs.(58.5±5.3)%, (87.4±8.7)mmol/L vs.(120.8±10.4)mmol/L, (8.6±1.7)mmol/L vs.(10.1±1.3)mmol/L, t=30.486, 20.609 and 5.864, P=0.000]. LVEF, TT3 and TT4 in patients with grade Ⅱ、grade Ⅲ and grade ⅣCardiac insufficiency were[(42.3±2.2)%、(37.9±1.0)% and(31.8±1.5)%, (104.2±15.4)mmol/L、(89.7±4.6)mmol/L and(72.0±7.2)mmol/L, (9.3±1.8)mmol/L、(8.8±1.3)mmol/L and(8.1±0.9)mmol/L]respectively. Serum levels of TT3 and TT4 and LVEF steadily declined as cardiac dysfunction grew more severe in patients with chronic heart failure(P=0.000). Conclusions Patients with chronic cardiac insufficiency are often combined with euthyroid sick syndrome, and serum levels of TT3 and TT4 can indicate the degree of abnormal cardiac systolic function. Therefore, low serum levels of T3 and T4 can be used as indicators for poor prognosis in patients with chronic heart failure. Key words: Thyroxine; Heart failure

A pair of peptides inhibits seeding of the hormone transporter transthyretin into amyloid fibrils

The tetrameric protein transthyretin is a transporter of retinol and thyroxine in blood, cerebrospinal fluid, and the eye, and is secreted by the liver, choroid plexus, and retinal epithelium, respectively. Systemic amyloid deposition of aggregated transthyretin causes hereditary and sporadic amyloidoses. A common treatment of patients with hereditary transthyretin amyloidosis is liver transplantation. However, this procedure, which replaces the patient's variant transthyretin with the WT protein, can fail to stop subsequent cardiac deposition, ultimately requiring heart transplantation. We recently showed that preformed amyloid fibrils present in the heart at the time of surgery can template or seed further amyloid aggregation of native transthyretin. Here we assess possible interventions to halt this seeding, using biochemical and EM assays. We found that chemical or mutational stabilization of the transthyretin tetramer does not hinder amyloid seeding. In contrast, binding of the peptide inhibitor TabFH2 to ex vivo fibrils efficiently inhibits amyloid seeding by impeding self-association of the amyloid-driving strands F and H in a tissue-independent manner. Our findings point to inhibition of amyloid seeding by peptide inhibitors as a potential therapeutic approach.