T4 Concentrations Research Articles

Influence of partial feeding of orange fleshed sweet potato root meal on the blood indices of finisher broiler chickens

Abstract A six-week study was conducted to evaluate the effects of partial replacement of maize with Orange Fleshed Sweet Potato (OFSP) root meal on the haematological parameters and serum biochemistry of broiler chickens at finisher phase. One hundred and eight (108) day old broiler chicks were randomly allotted into 4 dietary treatments (T1, T2, T3 and T4) with 3 replicates each and 9 birds per replicate. The test ingredient, OFSP root meal was included in broiler finisher diets as replacement for maize at 0%, 6%, 12% and 18% in the dietary treatments respectively. The study revealed no effect on all the haematological parameters. The result of the serum biochemistry also showed no significant differences (P>0.05) on all the parameters measured with the exception of triglycerides, globulin and blood urea nitrogen with significant decrease in the triglycerides (mg/dl) and globulin (g/dl) content of T2(24.80 and 0.37), T3(47.01 and 1.07) and T4(48.50 and 1.41) respectively as compared with the control group (61.54 and 1.95 respectively). Therefore, inclusion of OFSP root meal up to 18% did not negatively affect the haematological parameters of the birds and also reduced the risk of metabolic diseases in the birds while improving the cardiovascular health of the birds.

A minimal human physiologically based kinetic model of thyroid hormones and chemical disruption of plasma thyroid hormone binding proteins.

The thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), are under homeostatic control by the hypothalamic-pituitary-thyroid axis and plasma TH binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB). THBPs buffer free THs against transient perturbations and distribute THs to tissues. TH binding to THBPs can be perturbed by structurally similar endocrine-disrupting chemicals (EDCs), yet their impact on circulating THs and health risks are unclear. In the present study, we constructed a human physiologically based kinetic (PBK) model of THs and explored the potential effects of THBP-binding EDCs. The model describes the production, distribution, and metabolism of T4 and T3 in the Body Blood, Thyroid, Liver, and Rest-of-Body (RB) compartments, with explicit consideration of the reversible binding between plasma THs and THBPs. Rigorously parameterized based on literature data, the model recapitulates key quantitative TH kinetic characteristics, including free, THBP-bound, and total T4 and T3 concentrations, TH productions, distributions, metabolisms, clearance, and half-lives. Moreover, the model produces several novel findings. (1) The blood-tissue TH exchanges are fast and nearly at equilibrium especially for T4, providing intrinsic robustness against local metabolic perturbations. (2) Tissue influx is limiting for transient tissue uptake of THs when THBPs are present. (3) Continuous exposure to THBP-binding EDCs does not alter the steady-state levels of THs, while intermittent daily exposure to rapidly metabolized TBG-binding EDCs can cause much greater disruptions to plasma and tissue THs. In summary, the PBK model provides novel insights into TH kinetics and the homeostatic roles of THBPs against thyroid disrupting chemicals.

Exposure to environmentally relevant concentrations of TnBP results in tissue-specific bio-accumulation and inhibits growth of silver carp (Hypophthalmichthys molitrix)

Tri-n-butyl phosphate (TnBP) is commonly used as flame retardant and rubber plasticizer, and has been widely detected in aquatic organisms and natural waters. However, the potential toxicity of TnBP in fish remains unclear. In the present study, silver carp (Hypophthalmichthys molitrix) larvae were treated with environmentally relevant concentrations (100 or 1000 ng/L) of TnBP for 60 d and then they were depurated in clean water for 15 d, and the accumulation and depuration of the chemical in six tissues of silver carp were measured. Furthermore, effects on growth were evaluated and potential molecular mechanisms were explored. Results indicated that TnBP could be rapidly accumulated and depurated in silver carp tissues. In addition, the bio-accumulation of TnBP displayed tissue-specificity, where intestine contained the greatest and vertebra had the smallest level of TnBP. Furthermore, exposure to environmentally relevant concentrations of TnBP led to time- and concentration-dependent growth inhibition of silver carp, even though TnBP was completely depurated in tissues. Mechanistic studies suggested that exposure to TnBP up- and down-regulated the expression of ghr and igf1 in liver, respectively, and increased GH contents in plasma of silver carp. TnBP exposure also up-regulated the expression of ugt1ab and dio2 in liver, as well as decreased T4 contents in plasma of silver carp. Our findings provide direct evidence of health hazards of TnBP to fish in natural waters, calling for more attention of environmental risks of TnBP in aquatic environment.

Role of vitamin E and zinc sulfate in infertile men

Infertility affects 15-30% of couples that are trying to conceive, about half of these cases, male partner is the sole contributing factor. Infertility remains a controversial problem worldwide, male infertility caused by different anatomical defect like obstruction of seminal tube and neurological abnormalities, resulting in abnormal spermatogenesis which weakens the function of sperm.Follow-up study done for 60 infertile men with age range between 30-45 years. Data collected was carried out during the period from April 2019 to August 2019 in Bajii city which include seminal fluid analysis, determination of testosterone, prolactin, and T3 and T4 before and after treatment with vitamin E(800 I.U/daily) and zinc sulfate(50mg/daily) which last for three months , all data were presented as mean and standard deviation. In this study we exclude any disease or abnormal condition that related to this group.There are 60 infertile men participated in this study, age range between 30-45 years. In these cases we measured the seminal fluid analysis, determination of testosterone, prolactin, and T3 and T4 before and after treatment with vitamin E(800 I.U/daily) and zinc sulfate(50mg/daily) which last for three monthsAbout the seminal fluid analysis, there is a significant increase in number of sperm in infertile men after the treatment, and also there is a significant increase in activity of sperm after treatment. Regarding the seminal fluid analysis, there is a significant increase in number of sperm in infertile men after the treatment compared with this before treatment and also there is a significant increase in activity of sperm after treatment compared with this before treatment. About the percentage of non-motile sperm, there is a significant decrease in this percentage after treatment compared with this before treatment, also there is decrease in percentage of abnormal sperm shape after treatment compared with this before treatment, while there is a significant increase in percentage of normal sperm shape after treatment compared with this before treatment About the concentration of prolactin, there is none significant difference between its level after treatment and before treatment. Regarding the concentration of testosterone, there is a significant elevation in its concentration after the treatment compared with its concentration before treatment and About the concentration of T3 and T4, there is none significant difference in its concentration after treatment and before treatment respectively.

Evaluation of thyroid function in people vaccinated against COVID-19 via Sinofarm type

Background; Since the emergence of the coronavirus disease pandemic, several effective vaccines have been introduced. These vaccines work through several different immunogenic pathways to produce effective immunity. There have been a number of reports of patients developing sub-acute thyroiditis and thyroid dysfunction after receiving the coronavirus (COVID-19) vaccine. This study aims to demonstrate the physiological effect of the covid -19 vaccine on human thyroid hormone. Methodology; For this purpose, 25 samples of male and female blood from people vaccinated with the corona virus used, 25 samples of blood from unvaccinated people were considered as a control group. The effect of this vaccine on the functions of the thyroid gland and on the concentrations of hormones was shown. A significant increase in the concentration of hormone T4 was observed in the group of vaccinated people compared to the control group. Conclusion, the current study Showed that the level of hormones increased significantly in the vaccinated compared to the control group, as well as concluded these results was indicate that thyroid function is negatively affected by the vaccine.

Гипотиреоз у долгожителей: благо или вред?

Aim. To analyze the relationship of thyroid hormones with various clinical and laboratory parameters in centenarians with coronary artery disease (CAD) based on the determination of the blood concentration of thyroid-stimulating hormone (TSH), free triiodothyronine (T3) and free thyroxine (T4). Materials and methods. This work was a cross-sectional study conducted on the basis of the Hospital for War Veterans No. 3. The study enrolled 262 patients [195 (74.4%) women and 67 (25.6%) men] aged 90 to 101 years (mean age 92.9±2.5 years) hospitalized with a diagnosis of coronary artery disease. The concentration of thyroid-stimulating hormone (normal 0.27–4.2 μIU/ml), the level of free T4 (12–22 pmol/l) and free T3 (3.1–6.8 pmol/l) in the blood were determined. Results. The mean level of TSH was 3.1±3.1 μIU/ml (0.005–108), free T3 – 3.7±0.65 pmol/l (1.9–5.3), free T4 – 14.1±5.5 pmol/l (4.1–32). In 18.9% of patients, the level of TSH was elevated, in 3.9% it was reduced, in 77.2% of patients it was normal. In patients with increased TSH lower functional activity was noted, assessed using the Barthel index (66.9±23.0 compared to 75.0±16.4 points in patients with normal TSH; p=0.02) and the IADL scale (3.46±2.3 and 4.6±2.0 points, respectively; p=0.006). Direct correlations were registered between free T4 concentration and uric acid (r=0.28; p=0.05), cholesterol (r=0.35; p=0.01), triglycerides (r=0.37; p=0.08), hemoglobin (r=0.23; p=0.07) and Morse fall scale (r=0.34; p=0.05). Significant inverse correlations were established between the blood concentration of free T4 and absolute indicators of bone mineral density in the lumbar spine (r=-0.36; p=0.03), in the proximal left (r=-0.44; p=0.006) and right (r=-0.43; p=0.009) femur. Conclusion. The study results demonstrate the relationship between the concentration of thyroid hormones and various clinical and laboratory parameters in centenarians with coronary heart disease.

Sympathetic blockade on diet induced thermogenesis in the congenic LA/Ntul//-cp rat

The effects of overfeeding highly palatable diets via the cafeteria feeding diet method (Café) has been shown to be a reliable experimental model to induce diet induced thermogenesis (DIT) in young adult normally lean rats of several strains. Groups of young adult lean LA/Ntul//-cp rats were offered a Purina chow diet (CHOW) or the same diet plus a daily café supplement both ad libitum from 10 until 24 weeks of age. The drug α-methylparatyrosine (α-MPT) was administered to groups (250 mg α-MPT/kg BW, i.p.) to ablate sympathetic (SNS) activity or a sham injection of physiologic saline given, and measures of fasting resting thermogenesis obtained at thermal neutrality (30°C) before and after the α-MPT or sham administration. The Café diet resulted in a 67% increase in body weight (BW) and a ~25% increase in resting oxygen consumption (VO2) following café overfeeding in both groups, while only a 40% increase in BW and no additional increase in VO2 occurred in normally CHOW fed rats while the sham injection was without any variations from normal physiologic responses as predicted. Sympathetic blockade with α-MPT was associated with modest decreases in body temperature and an average ~12-15% decrease in VO2 in the café treated group, but when the VO2 data were arithmetically corrected to isothermal conditions only a net 3% decrease occurred in CHOW fed rats and was without effect on the SHAM group. Serum T3 concentrations increased by 92% and urinary catecholamine excretion of VMA >250% following the café diet, but the urinary vanilmandelic acid (VMA) excretion was virtually nil following the sympathetic blockade. These observations indicate that the SNS-mediated contribution component to DIT following prolonged café overfeeding under conditions of thermal neutrality contribute approximately 50% of the thermic response. while under normal long term CHOW feeding the SNS component may be as little as 3 % of the thermic response, and thus, the total thermic response of DIT likely represents a combination of short acting SNS and longer acting non-SNS mechanisms, including a likely significant thyroidal component in normally lean animals.

Chalcone T4 Inhibits RANKL-Induced Osteoclastogenesis and Stimulates Osteogenesis In Vitro.

Chalcones are phenolic compounds produced during the biosynthesis of flavonoids that have numerous biological activities, including anti-inflammatory, antioxidant and anticancer. In this in vitro study, we investigate a newly synthesized chalcone (Chalcone T4) in the context of bone turnover, specifically on the modulation of osteoclast differentiation and activity and osteoblast differentiation. Murine macrophages (RAW 264.7) and pre-osteoblasts (MC3T3-E1) were used as models of osteoclasts and osteoblasts, respectively. Differentiation and activity osteoclasts were induced by RANKL in the presence and absence of non-cytotoxic concentrations of Chalcone T4, added in different periods during osteoclastogenesis. Osteoclast differentiation and activity were assessed by actin ring formation and resorption pit assay, respectively. Expression of osteoclast-specific markers (Nfatc1, Oscar, Acp5, Mmp-9 and Ctsk) was determined by RT-qPCR, and the activation status of relevant intracellular signaling pathways (MAPK, AKT and NF-kB) by Western blot. Osteoblast differentiation and activity was induced by osteogenic culture medium in the presence and absence of the same concentrations of Chalcone T4. Outcomes assessed were the formation of mineralization nodules via alizarin red staining and the expression of osteoblast-related genes (Alp e Runx2) by RT-qPCR. Chalcone T4 reduced RANKL-induced osteoclast differentiation and activity, suppressed Oscar, Acp5 and Mmp-9 expression, and decreased ERK and AKT activation in a dose-dependent manner. Nfact1 expression and NF-kB phosphorylation were not modulated by the compound. Mineralized matrix formation and the expression of Alp and Runx2 by MC3T3-E1 cells were markedly stimulated by Chalcone T4. Collectively, these results demonstrate that Chalcone T4 inhibits in osteoclast differentiation and activity and stimulates osteogenesis, which indicates a promising therapeutic potential in osteolytic diseases.

Critical Approach to Hypothyroid Patients With Persistent Symptoms.

Hypothyroidism is a common condition, and numerous studies have been published over the last decade to assess the potential risks associated with this disorder when inappropriately treated. The standard of care for treatment of hypothyroidism remains levothyroxine (LT4) at doses to achieve biochemical and clinical euthyroidism. However, about 15% of hypothyroid patients experience residual hypothyroid symptoms. Some population-based studies and international population-based surveys have confirmed dissatisfaction with LT4 treatment in some hypothyroid patients. It is well established that hypothyroid patients treated with LT4 exhibit higher serum thyroxine:triiodothyronine ratios and can have a persistent increase in cardiovascular risk factors. Moreover, variants in deiodinases and thyroid hormone transporter genes have been associated with subnormal T3 concentrations, persistent symptoms in LT4-treated patients, and improvement in response to the addition of liothyronine to LT4 therapy. The American (ATA) and European Thyroid Association (ETA) guidelines have recently evolved in their recognition of the potential limitations of LT4. This shift is reflected in prescribing patterns: Physicians' use of combination therapy is prevalent and possibly increasing. Randomized clinical trials have recently been published and, while they have found no improvement in treating hypothyroid patients, a number of important limitations did not allow generalizability. Meta-analyses have reported a preference rate for combination therapy in 46.2% hypothyroid patients treated with LT4. To promote discussions about an optimal study design, the ATA, ETA, and British Thyroid Association have recently published a consensus document. Our study provides a useful counterpoint on the controversial benefits of treating hypothyroid patients with combination therapy.

Effect of Ground Addition of Seaweed Extract and NPK Fertilizer on the Vegetative Growth Characteristics of Aloe vera L.

To investigate the impact of ground application of seaweed extract and NPK fertilizer on some vegetative growth characteristics of Aloe vera, an experiment was conducted during the agricultural season (2021-2022) in the wooden canopy of the Department of Horticulture and Garden Engineering at the College of Agriculture / University of Karbala. The experiment had two factors: the addition of fertilizer to the neutralized NPK at three concentrations (4, 2, 0) g.L-1, and the employment of an environmentally friendly nutritional program by adding seaweed powder to the chemical program of adding NPK fertilizer neutralized 20:20:20 L-1. The following emerged from the experiment’s findings: (1) The ground addition of seaweed extract of the aloe vera plant led to a significant increase in all vegetative characteristics when treated T3 concentration (3 g. L-1) (plant height 32.11 cm, leaf thickness 10.93 mm, number of leaves 12.56 leaves plant-1, fresh weight 167.78 g, leaf dry weight 55.89 g). (2) The results showed that the addition of the neutral NPK fertilizer to the aloe vera plant at a concentration of (4 g / l-1) when treated, showed significant differences in all vegetative growth characteristics (plant height (30.60) cm ،the thickness of the leaf is 9.86 mm, the number of leaves is 12.11 leaves. Plant, the fresh weight is 158.00 g, the dry weight of the leaf is 52.53 g). (3)The binary interaction between the addition of seaweed extract and NPK fertilizer when the interaction T3N4 (4g/l-1 + 3 4g/l-1) showed significant differences in all vegetative characteristics of aloe vera plant، (Plant height 34.83 cm, leaf thickness 12.73 mm, number of leaves 15.00 leaf. Plant, fresh weight 174.33 gm, dry weight 58.07 gm.

Alterations of Thyroid Hormone Levels and the Risks of Diabetic Retinopathy in T2DM

Background: Diabetes mellitus and thyroid disease are linked endocrinopathies. The association between diabetes mellitus complications and thyroid function is characterized by a complicated interdependent interplay that is difficult to understand. Objective: We conducted this study to determine the association between diabetic retina disease (DRD) incidence and normal thyroid hormone levels in T2DM. Methods: Recruit patients in the study, 134 patients with type 2 diabetes and 36 healthy ones with no DM, were screened in the present case-control study. Diabetic retinopathy was tested for all patients, and anthropometric and thyroid functions were assessed. Regression analyses were employed to evaluate the relationship between thyroid hormones and the risk of developing DR. Results: There were significant differences in triiodothyronine (T3) and thyroxine (T4) serum levels among the DR groups and the healthy control. The levels in each TSH and T4 are positively significant between groups of PDR and NDR, while T3 was negatively associated with NPDR. A significant association was found between increasing levels of T3 and the development of severe DR; thus, PDR was less likely to occur in individuals with high T3 levels‎ [OR 0.014(95% CI, 0.001-0.34) P value is 0.009 after adjustment. The risk of PDR had an increased likelihood of developing PDR at the highest levels of serum TSH and T4 [OR 41.07(1.60-1053.1) P= 0.025, OR 65.91(2.10-2067) P= 0.017, respectively). Conclusion: Diabetes retinopathy in euthyroid Iraqi people may be associated with levels of T3 and T4 in the blood. Patients with higher TSH and T4 concentrations had a greater risk of developing sight-threatening PDR in type 2 diabetics.

Treatment of Subclinical Hypothyroidism; A Review of Literature

Background: Subclinical hypothyroidism (SCH) is a disorder without any symptoms related with an elevated thyroid stimulating hormone (TSH) concentration > 4 mIU/l and normal T4 and T3 concentrations. It is communal in the elderly and particularly in females, with prevalence of about 11%. Some studies show no effect of the treatment, while others have found it to be beneficial, since normal TSH levels can be above 7.5 mIU/L in the elderly. As a result of these findings, the best treatment for SCH, especially in elderly patients, has been criticized. Aim: The aim of this study was to evaluate the latest literature on the subject in order to assess the available evidence regarding this controversy in order to determine whether and under what conditions treatment of SCH is essential and how it can be prevented. Methods: To better understand the ongoing debate regarding the treatment of SCH, a Medline search of the English-language literature was held between 2015 and 2022 using the terms subclinical hypothyroidism, hypothyroidism, treatment and prevention, cardiovascular disease, dyslipidemia and cardiac failure. From this search, 38 articles with relevant material were selected. Results: When the data from these studies were combined, it was found that normal TSH levels increased with age, from 4 to 7.5 mIU/L in subjects under 75 years of age. Levothyroxine supplementation has also shown marked effects on the metabolic and clinical features of SCH, including decline in cardiovascular disease, heart failure, and mortality, although many of the peer-reviewed articles exhibited no treatment benefit. The drug works best in younger people who also experience fewer side effects. Conclusions: Younger patients with TSH > 4.0 mIU/l should be treated for SCH based on available data. Treatment must be modified according to the TSH levels and existence of symptoms, and should be started with a TSH level of 10 mIU/L with moderate doses to minimize adversative cardiovascular complications in elderly patients. Keywords: subclinical, discussion, thyroxine, treatment, hypothyroidism, hypertension, thyrotropin, dyslipidemia, heart failure, cardiovascular diseases, prevention.

Study on Bacteriological Measurement of Clean Water in Raja Ampat

The availability of clean water is a right that must be obtained by all humans. Unfortunately, some water sources in Indonesia are polluted by total coliform and Escherichia coli and threaten health. This study aims to measure total coliform and Escherichia coli in the Weisai sub-district, Raja Ampat Regency, West Papua province as an effort to monitor environmental quality. This research is an observational study with a quantitative approach. Primary data in this study is the measurement of total coliform and Escherichia coli. The samples used were clean water in the borehole well of Bambang Sutejo village (T1); the dug well of Nyonya Fransina village (T2); and the dug well of Om Miter village (T3). Sample testing was conducted by the Environmental Health and Disease Control Technical Center (BTKLPP), Ambon City, and taken on November 28, 2022. The test results obtained, total coliform parameters of 1,600 MPN/100 mL and Escherichia coli 2.2 at T1. Meanwhile, the T3 concentration of total coliform and Escherichia coli exceeded 1,600 MPN/100 mL. T1 and T3 have values that exceed quality standards. This is due to livestock waste that does not have a wastewater disposal channel and the absence of communal domestic wastewater disposal channels

Thyroid evaluation in suspicious hypothyroid adult dogs before and after treatment.

The purpose of this study was to measure circulating TSH, T4 and fT4 concentrations in dogs submitted to a clinical visit for general symptoms (weight gain, polyuria and polydipsia, changes in hair coat). Twenty-eight dogs, 14 cross-breed and 14 purebreds (Golden Retriever, Labrador, Doberman), of both sexes (14 males and 14 females), aged 8 to 14 years, were assessed. No significant differences of circulating TSH, T4 , fT4 concentrations between the baseline and after therapeutic treatment nor between intact and neutered females were observed. Compared to baseline values, intact males showed higher TSH concentrations (p⟨0.01), and castrated males lower TSH concentrations (p⟨0.01) after therapeutic treatment. Compared to intact males, castrated males showed baseline TSH concentrations higher (p⟨0.01), but lower (p⟨0.01) after therapeutic treatment. No significant differences of T4 and fT4 concentrations between baseline conditions and after therapeutic treatment, nor between intact and castrated males, were observed. The experimental sample considered in this study falls within that casuistry involving elevated TSH concentrations but low serum T4 and fT4 concentrations or close to the minimum physiological cut-off, in which the common clinical signs suggestive of hypothyroidism was, essentially, overweight and neglected appearance of the hair.

Compare the Effectiveness of Carbimazole Single Dose and Divided Dose Regimens for Euthyroid Induction in Hyperthyroid Patients

Objective: The purpose of the current study was to examine the effectiveness of carbimazole administered as a single dose with a divided dose regimen for inducing euthyroidism in hyperthyroid patients. Study Design: Prospective/Randomized study Place and Duration: This Prospective/Randomized study was conducted at Khyber Teaching Hospital Peshawar in the duration from June, 2022 to November, 2022. Methods: There were 92 patients of hyperthyroidism were presented in this study. Age, sex, BMI, and residency details for each enrolled case were recorded after receiving informed written consent. Patients were divided into two groups equally. Carbimazole (OD-CMZ) was administered as a single dosage to 46 patients in group I, and as two separate doses to 46 patients in group II (DD-CMZ). For six months, the effectiveness of the treatment was monitored on a regular basis (every four weeks). SPSS 22.0 was used to analyze all data. Results: There were 54 (58.7%) females and 38 (41.3%) males in this study. In group I mean age was 35.13±6.60 years and in group II mean age was 40.10±8.86 years. Mean duration of disease was 3.6±10.57 months in group I and in group II mean duration was 4.3 ±8.35 months. There was no discernible difference between the two groups in terms of baseline TSH and T4 concentrations or their cumulative rates of reduction (p-value, 0.014). Frequency of euthyroidism in group I after final follow up was 46 (100%) and in group II found in 45 (97.8%) cases but difference is insignificance. Conclusion: In this study, we came to the conclusion that a single dosage regimen is a more effective way to treat hyperthyroidism since there is no discernible difference in efficacy and a greater risk of developing hypothyroidism with a split dose strategy. Keywords: Hyperthyroidism, Drug therapy, Single dose, Carbimazole, Multidose

Hypothyroidism impairs development of the gastrointestinal tract in the ovine fetus.

Growth and maturation of the fetal gastrointestinal tract near term prepares the offspring for the onset of enteral nutrition at birth. Structural and functional changes are regulated by the prepartum rise in cortisol in the fetal circulation, although the role of the coincident rise in plasma tri-iodothyronine (T3) is unknown. This study examined the effect of hypothyroidism on the structural development of the gastrointestinal tract and the activity of brush-border digestive enzymes in the ovine fetus near term. In intact fetuses studied between 100 and 144days of gestation (dGA; term ∼145days), plasma concentrations of T3, cortisol and gastrin; the mucosal thickness in the abomasum, duodenum, jejunum and ileum; and intestinal villus height and crypt depth increased with gestational age. Removal of the fetal thyroid gland at 105-110 dGA suppressed plasma thyroxine (T4) and T3 concentrations to the limit of assay detection in fetuses studied at 130 and 144 dGA, and decreased plasma cortisol and gastrin near term, compared to age-matched intact fetuses. Hypothyroidism was associated with reductions in the relative weights of the stomach compartments and small intestines, the outer perimeter of the intestines, the thickness of the gastric and intestinal mucosa, villus height and width, and crypt depth. The thickness of the mucosal epithelial cell layer and muscularis propria in the small intestines were not affected by gestational age or treatment. Activities of the brush border enzymes varied with gestational age in a manner that depended on the enzyme and region of the small intestines studied. In the ileum, maltase and dipeptidyl peptidase IV (DPPIV) activities were lower, and aminopeptidase N (ApN) were higher, in the hypothyroid compared to intact fetuses near term. These findings highlight the importance of thyroid hormones in the structural and functional development of the gastrointestinal tract near term, and indicate how hypothyroidism in utero may impair the transition to enteral nutrition and increase the risk of gastrointestinal disorders in the neonate.

Adverse thyroid hormone and behavioral alterations induced by three frequently used synthetic musk compounds in embryo-larval zebrafish (Danio rerio)

Synthetic musk compounds (SMCs) have been extensively used in numerous consumer products, such as perfumes, cosmetics, soap, and fabric softener. Due to their bioaccumulative nature, these compounds have often been detected in the aquatic ecosystem. However, their effects on endocrine and behavioral effects in freshwater fish have rarely been investigated. In the present study, thyroid disruption and neurobehavioral toxicity of SMCs were investigated using embryo-larval zebrafish (Danio rerio). Three frequently used SMCs, i.e., musk ketone (MK), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta [g]- benzopyran (HHCB), and 6-acetyl-1,1,2,4,4,7-hexamethyltetralin (AHTN), were chosen. Experimental concentrations for HHCB and AHTN were selected to include the maximum levels reported in the ambient water. The 5-day exposure to either MK or HHCB led to significant decrease of T4 concentration in the larval fish at the levels as low as 0.13 μg/L, even though compensatory transcriptional changes, e.g., up-regulation of hypothalamic crhβ gene and/or down-regulation of ugt1ab gene, were taken place. In contrast, AHTN exposure resulted in up-regulation of crhβ, nis, ugt1ab, and dio2 genes but did not alter T4 level, suggesting its lesser thyroid disrupting potential. All tested SMCs caused hypoactivity of the larval fish. Several genes related to neurogenesis or development, e.g., mbp and syn2a, were down-regulated, but the patterns of transcriptional changes were different among the tested SMCs. The present observations demonstrate that MK and HHCB can decrease T4 levels and cause hypoactivity of the larval zebrafish. It requires attention that HHCB and AHTN could influence thyroid hormone or behavior of the larval fish even at the levels close to those observed in the ambient environment. Further studies on potential ecological consequences of these SMCs in freshwater environment are warranted.

Rat Serum Osteocalcin Concentration Is Decreased by Restriction of Energy Intake

We studied the effects of energy restriction on serum osteocalcin concentration and bone formation rate in rats. The experiment was designed to achieve energy restriction by reducing the carbohydrate intake while providing identical quantities of protein, fat, vitamins and minerals. Energy intakes of three groups of post-weaning male rats were restricted by 20, 40 and 60% for 4 wk. Serum calclum, phosphorus, transthyretin, triiodothyronine (T3), thyroxine (T4), 1,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol and immunoreactive parathyroid hormone (iPTH) concentrations were determined. Energy restriction (20, 40 and 60%) produced a significant and gradual drop of serum osteocalcin concentrations, although the serum concentrations of its key regulators, i.e., 1,25-dihydroxycholecalciferol and iPTH, were not significantly affected. On the contrary, serum concentrations of calcium, phosphorus, transthyretin, T3 and T4 were significantly lower in the energy-restricted groups. However, our results do not support their implication in the regulation of serum osteocalcin synthesis by energy intake. Serum osteocalcin concentration was positively correlated with bone mineral apposition (r = 0.50, P < 0.05) and bone mineralization (r = 0.50, P < 0.05) rates suggesting that its decrease resulted from a reduction of bone formation, and not from abnormal mineralization, because osteoid seam thickness was not modified. Energy intake seems to be an important determinant of serum osteocalcin concentration and bone formation; however, the exact mechanism underlying this regulation remains to be determined.

Dietary Supplementation of Chestnut Tannins in Prepartum Dairy Cows Improves Antioxidant Defense Mechanisms Interacting with Thyroid Status.

Cows in the peripartal period undergo changes in thyroid hormones and are susceptible to lipomobilization and/or oxidative stress. The addition of chestnut tannins as polyphenolic compounds in the diet may improve feed efficiency and prevent oxidative stress-related health disorders in transition cows. However, the relationship between chestnut tannin supplementation and thyroid function, which plays an important role in metabolic regulation, has not been investigated in dairy cows. This study was conducted to investigate the effects of chestnut tannin supplementation during the close-up period on thyroid status and to evaluate the interaction between thyroid hormones and oxidative stress biomarkers in prepartum dairy cows. Forty multiparous Holstein cows were fed either a diet containing chestnut tannins (CNTs, n = 20, 1.96 g chestnut tannins/kg feed, dry matter) or a non-supplemented diet (CON, n = 20) during the last 25 ± 2 days of gestation. Blood samples were collected on the first day of study (before chestnut tannin supplementation) and d 5 before parturition to measure hormonal and oxidative stress indices. Serum concentrations of T3 (p = 0.04) and T4 (p = 0.05) were higher in CNT cows than in the CON group on day 5 before parturition. Thyroid status of CNT cows was associated with higher serum total antioxidant capacity (T-AOC, p < 0.01), activities of superoxide dismutase (SOD, p = 0.03) and glutathione peroxidase (GPx, p = 0.01), and reduced glutathione concentration (GSH, p = 0.05). Serum thiobarbituric acid reactive substances (TBARS) were lower (p = 0.04) which was associated with lower aspartate aminotransferase (AST, p = 0.02), and lactate dehydrogenase (LDH, p = 0.01) activities in the CNT than in the CON group. Estradiol and progesterone did not differ between CNT and CON cows. Chestnut tannin supplementation improves antioxidant protection, prevents oxidation-reduction processes, reduces the degree of liver cell membrane damage, and protects thyroid tissue from damage, allowing higher T3 and T4 synthesis. Considering the importance of the thyroid hormone status before parturition, mechanisms of thyroid hormone regulation in CNT-supplemented dairy cows require more detailed investigations.

Thyroid hormone triiodothyronine does not protect ovarian reserve from DNA damage induced by X-ray and cisplatin.

Cancer therapy can induce premature ovarian insufficiency, necessitating methods for preserving fertility in female cancer patients. However, the only accepted clinical practice for doing so is cryopreservation of embryos, unfertilized ova, and ovarian tissue, despite potential options such as in vitro maturation of follicles. Therefore, considerable interest has arisen in fertoprotective agents, with research on rat ovarian granulosa cells suggesting that triiodothyronine (T3) regulates an anti-apoptosis mechanism that protects the ovarian reserve from paclitaxel-induced DNA damage. In this study, we used postnatal day 5 mouse ovary to confirm the existence of T3 thyroid hormone receptor (THR), as well as to investigate the potential protective effects of T3 against cisplatin- and X-ray-induced apoptosis. We also tested the potential anti-apoptotic effect of T3 in the breast cancer cell line MDA-MB-231. We treated cultured mouse ovaries with varying concentration of T3 and 4μM cisplatin and 0.2Gy X-ray. Real-time PCR, histological analysis, immunoblot analysis, and immunofluorescence were performed to assess the potential anti-apoptotic effects of T3. We confirmed that THR alpha and beta are expressed in the mouse ovary. T3 (0.1, 1, 10, 100nM, and 1µM) does not protect ovarian reserve from cisplatin- or X-ray-induced apoptosis or DNA damage. Similarly, it does not protect mouse granulosa cells and MDA-MB-231 cells from cisplatin- or X-ray-induced apoptosis. Our findings suggest that T3 is ineffective as a fertoprotective agent, and its candidacy as a potential agent to preserve fertility should be reconsidered.