T3 Supplementation Research Articles

Perfluoropolyether carboxylic acids (novel alternatives to PFOA) impair zebrafish posterior swim bladder development via thyroid hormone disruption

Perfluoropolyether carboxylic acids (PFECAs, CF3(OCF2)nCOO−, n = 2–5) are novel alternatives to perfluorooctanoic acid (PFOA) and are widely used in industrial production. However, although they have been detected in surface water and human blood, their toxicities on aquatic organisms remain unknown. We used zebrafish embryos to compare the developmental toxicities of various PFECAs (e.g., perfluoro (3,5,7-trioxaoctanoic) acid (PFO3OA), perfluoro (3,5,7,9-tetraoxadecanoic) acid (PFO4DA), and perfluoro (3,5,7,9,11-pentaoxadodecanoic) acid (PFO5DoDA)) with that of PFOA and to further reveal the key events related to toxicity caused by these chemicals. Results showed that, based on half maximal effective concentrations (EC50), toxicity increased in the order: PFO5DoDA > PFO4DA > PFOA > PFO3OA, with uninflated posterior swim bladders the most frequently observed malformation. Similar to PFOA, PFECA exposure significantly lowered thyroid hormone (TH) levels (e.g., T3 (3,5,3′-L-triiodothyronine) and T4 (L-thyroxine)) in the whole body of larvae at 5 d post-fertilization following disrupted TH metabolism. In addition, the transcription of UDP glucuronosyltransferase 1 family a, b (ugt1ab), a gene related to TH metabolism, increased dose-dependently. Exogeneous T3 or T4 supplementation partly rescued PFECA-induced posterior swim bladder malformation. Our results further suggested that PFECAs primarily damaged the swim bladder mesothelium during early development. This study is the first to report on novel emerging PFECAs as thyroid disruptors causing swim bladder malformation. Furthermore, given that PFECA toxicity increased with backbone OCF2 moieties, they may not be safer alternatives to PFOA.

Effects of L-threonine and L-tryptophan supplementation on the body weight and internal organs weight of native chickens aged 14 weeks

The aim of this study was to determine the effect of L-threonine and L-tryptophan supplementation on the body weight and internal organs weight of native chickens aged 14 weeks. The experiment used 112 six-week old native chickens. They were allocated to four treatments and four replicates. The four dietary treatments were: (1) T0 (control); (2) T1 (supplementation of 0.25% L-threonine and 0.07% L-tryptophan); (3) T2 (supplementation of 0.58% L-threonine and 0.14% L-tryptophan); and (4) T3 (supplementation of 0.85% L-threonine and 0.20% L-tryptophan). The result showed that the body weight of T0, T1, T2 and T3 were 1044.28, 1081.91, 1115.95 and 1151.34 g/bird, respectively. The liver, pancreas, and gizzard weights and the intestinal length were 2.56, 2.66, 2.81 and 2.91 g/bird; 3.90, 4.17, 4.43 and 4.46 g/bird; 26.00, 28.63, 30.26 and 31.28 g/bird; 124.80, 131.90, 137.88 and 139.73 cm/bird, respectively. The result indicated that the body weight, liver, gizzard, and intestinal length affected by level of L-threonine and L-tryptophan (P<0.01). It was concluded that supplementation with 0.85% L-threonine and 0.20% L-tryptophan to the diet of native chickens resulted in optimal body weight and internal organs weight at 14 weeks.

Cardioprotective effects of triiodothyronine supplementation against ischemia reperfusion injury by preserving calcium cycling proteins in isolated rat hearts.

Hypothyroidism is associated with profound left ventricular dysfunction. Triiodothyronine (T3) supplementation may improve cardiac function after ischemic reperfusion (I/R) injury. In the present study, the effect of T3 on major calcium cycling proteins and high-energy phosphate content during I/R was evaluated. Isolated perfused rat hearts were divided into 5 groups: Sham Control (Sham, n=10), Control (n=8), T3 10 nM (T3-10, n=10), T3 25 nM (T3-25, n=10) and T3 50 nM (T3-50, n=10). T3 was administrated for 60 min before 30 min of ischemia and 120 min of reperfusion. The protein contents of Ca2+-release channels (RyR2), Ca2+-adenosine triphosphatase (SERCA2a), phospholamban (PLB), sarcolemmal Ca2+-adenosine triphosphatase (PMCA) and sodium-calcium exchanger (NCX), as well as the high-energy phosphate content in heart tissues were measured by western blot analysis. The results revealed that T3 improved the contractile recovery (left ventricular developed pressure; +dP/dt, -dP/dt) after I/R. Western blotting assays demonstrated that I/R depressed the contents of RYR2, SERCA2a and phosphorylated RYR2 and PLB; there were no effects on the contents of PLB, PMCA and NCX. T3 reversed I/R-induced degradation of RyR2 and SERCA2a, restored the phosphorylation of RyR2 and PLB, and preserved the high-energy phosphate contents of ATP and creatine phosphate. T3 supplementation protected the heart against I/R injury via the preservation of Ca2+-cycling proteins and high-energy phosphate content.

Oral Triiodothyronine Supplementation Decreases Low Cardiac Output Syndrome After Pediatric Cardiac Surgery.

The oral triiodothyronine for infants and children undergoing cardiopulmonary bypass (OTICC) trial showed that Triiodothyronine (T3) supplementation improved hemodynamic and clinical outcome parameters. We tested the validity of low cardiac output syndrome (LCOS), derived using clinical parameters and laboratory data, by comparing the LCOS diagnosis with objective parameters commonly measured in a cardiac intensive care unit (CCU) setting. OTICC, a randomized, placebo-controlled trial included children younger than 3years with an Aristotle score between 6 and 9. We used the existing trial data set to compare the LCOS diagnosis with echocardiographic hemodynamic parameters. Additionally, we determined if LCOS, prospectively assigned during a clinical trial, served as an early predictor of clinical outcomes. All LCOS subjects at 6 and 12h after cross-clamp release later showed significantly lower pulse pressure, stroke volume and cardiac output, and higher systemic vascular resistance. These LCOS patients also had significantly longer time to extubation (TTE) and higher mortality rate. LCOS incidence was significantly lower in the T3 treatment group [n = 86 vs. 66, respectively, p < 0.001; OR (95% CI) 0.43 (0.36-0.52)] particularly at 6h. Also, LCOS patients in the placebo group had significantly lower FT3 serum levels over time. These analyses confirm that early clinically defined LCOS successfully predicts cardiac dysfunction determined later by objective hemodynamic echocardiographic parameters. Furthermore, early LCOS significantly impacts TTE and mortality. Finally, the data support prior clinical trial data, showing that oral T3 supplementation decreases early LCOS in concordance with reducing TTE.

Hypothyroidism-related zinc deficiency leads to suppression of T lymphocyte activity.

Hypothyroidism has been shown to induce immunosuppression and both the thyroid status and immunity are affected by zinc deficiency. However, the impact of hypothyroidism on zinc metabolism and its possible relationship with the immune status has not yet been deeply explored. Here, our aim was to study whether hypothyroidism may alter zinc metabolism and thus lead to the impairment of T lymphocyte activity. Variations in the distribution of zinc in the body were evaluated in PTU-treated hypothyroid mice. The effects of hypothyroidism and zinc deficiency were studied on T lymphocyte proliferation after stimulation both in vitro and in vivo. For in vitro assays, thyroid hormone-free or zinc chelator (TPEN or DTPA)-supplemented media were used. For in vivo assays, lymphocyte activity was evaluated in cells from hypothyroid, T3-treated, and zinc-supplemented mice. Hypothyroid mice showed lower levels of zinc in femur and lymph nodes than controls. T3 and zinc supplementation reversed these effects. In vitro, both thyroid hormone and zinc deficiency led to a decreased response to mitogen stimulation. However, only zinc deficiency was able to induce lymphocyte apoptosis. Mitogen-stimulated T cells from hypothyroid mice showed impaired proliferation, accompanied by decreased activation of PKC and lower levels of p-ERK, effects that were reversed by T3 replacement or zinc supplementation. Our results show an important role of zinc deficiency in hypothyroid-mediated T-cell suppression and suggest the importance of evaluating zinc levels and restoring them when necessary to maintain an efficient immune response in hypothyroid patients.

Disruption of deiodinase type 2 in zebrafish disturbs male and female reproduction.

Thyroid hormones are crucial mediators of many aspects of vertebrate life, including reproduction. The key player is the biologically active 3,5,3'-triiodothyronine (T3), whose local bio-availability is strictly regulated by deiodinase enzymes. Deiodinase type 2 (Dio2) is present in many tissues and is the main enzyme for local T3 production. To unravel its role in different physiological processes, we generated a mutant zebrafish line, completely lacking Dio2 activity. Here we focus on the reproductive phenotype studied at the level of offspring production, gametogenesis, functioning of the hypothalamic-pituitary-gonadal axis and sex steroid production. Homozygous Dio2-deficient zebrafish were hypothyroid, displayed a delay in sexual maturity, and the duration of their reproductive period was substantially shortened. Fecundity and fertilization were also severely reduced. Gamete counts pointed to a delay in oogenesis at onset of sexual maturity and later on to an accumulation of oocytes in mutant ovaries due to inhibition of ovulation. Analysis of spermatogenesis showed a strongly decreased number of spermatogonia A at onset of sexual maturity. Investigation of the hypothalamic-pituitary-gonadal axis revealed that dysregulation was largely confined to the gonads with significant upregulation of igf3, and a strong decrease in sex steroid production concomitant with alterations in gene expression in steroidogenesis/steroid signaling pathways. Rescue of the phenotype by T3 supplementation starting at 4 weeks resulted in normalization of reproductive activity in both sexes. The combined results show that reproductive function in mutants is severely hampered in both sexes, thereby linking the loss of Dio2 activity and the resulting hypothyroidism to reproductive dysfunction.

Combined supplementation of ascorbic acid and thyroid hormone T3 affects tenocyte proliferation. The effect of ascorbic acid in the production of nitric oxide

Combined supplementation of ascorbic acid and thyroid hormone T3 affects tenocyte proliferation. The effect of ascorbic acid in the production of nitric oxide

Levothyroxine Therapy Achieves Physiological FT3/FT4 Ratios at Higher than Normal TSH Levels: A Novel Justification for T3 Supplementation?

In euthyroidism, as thyroid Stimulating hormone (TSH) levels increase, the free triiodothyronine (FT3) to free thyroxine (FT4) ratio increases. The aim of this study was to assess if beyond the euthyroid range of TSH levels FT3/FT4 ratio continues to increase and if levothyroxine treatment reduces this ratio, possibly through TSH suppression. This cross sectional retrospective study included a total of 77 832 patients [age 22.76±15.17 years (4 days to 112 years)] evaluated and treated in community clinics between January 2009 and September 2013. Blood samples drawn in community clinics for which TSH, FT4, FT3, age, and gender were available were included. Tests with TSH below 0.5 IU/l were excluded as were samples taken during pregnancy. The FT3/FT4 ratio continued to increase significantly even with TSH above 50 mIU/l (p for trend<0.001) with an increase of more than 50% over the entire TSH range. With increasing age and female gender, the phenomenon was less prominent (p<0.001). Levothyroxine treated patients had significantly lower FT3/FT4 ratios in comparison to untreated patients up to TSH levels of 5.0 mIU/l. In conclusion, increasing TSH increases FT3/FT4 ratio even with severe hypothyroidism, less so with aging. With levothyroxine therapy, a ratio similar to untreated patients is achieved at TSH of above 5.0 mIU/l. Since T3 suppresses TSH better than T4, administration of T3 would likely normalize the FT3/FT4 ratio at a lower, ostensibly more physiological, TSH level. This could be seen as a rationale for add-on T3 therapy.

Integrative analysis of differentially expressed genes and miRNAs predicts complex T3-mediated protective circuits in a rat model of cardiac ischemia reperfusion

Thyroid hormone (T3) dyshomeostasis in the cardiac ischemia-reperfusion (IR) setting negatively impacts on mitochondria function and extracellular matrix remodeling. The modulation of cardiac miRNAs may represent the underlying molecular mechanisms, but a systems biology perspective investigating this critical issue in depth is still lacking. A rat model of myocardial IR, with or without an early short-term T3-replacement, was used to predict putative T3-dependent miRNA-gene interactions targeted to mitochondria quality control and wound healing repair. As evidenced by mRNA and miRNA expression profiling, the T3 supplementation reverted the expression of 87 genes and 11 miRNAs that were dysregulated in the untreated group. In silico crossing and functional analysis of the T3-associated differentially expressed transcripts, identified a signature of interconnected miRNA-gene regulatory circuits that confer resistance to noxious cascades of acute stress. In this network the T3-down-regulated Tp53, Jun and Sp1 transcription factors emerge as critical nodes linking intrinsic cell death and oxidative stress pathways to adverse remodeling cascades. The data presented here provide a novel insight into the molecular basis of T3 cardioprotection in the early post-IR phase and highlight the contribution of a previously unappreciated complex T3-regulatory network that may be helpful in translating T3 replacement into clinical practice.

TGF-β4 and HSP70 responses in breeder hens treated with thyroxine

A hypothesis was tested that long-term administration of thyroxine (T4) in broiler breeder hens would affect fertility, sperm penetration rate, and the duration of fertility. Relative abundance of oviductal TGF-β4 and HSP70 mRNA was determined to ascertain whether T4 treatment affected these genes, and modulated the sustained storage of spermatozoa within the uterovaginal sperm storage tubules of hens. A total of 70, 47-week-old Cobb 500 breeder hens was randomly allotted to two treatment groups (T4 treatment (ET) and control). The T4 was orally administered to the ET group (0.3 mg T4/bird/day) for 100 consecutive days; whereas the control group was not administered T4 during the experimental period. Breeder hens were artificially inseminated to evaluate specific reproductive variables. On the last day of the treatment period two hens /replicate were randomly killed to estimate oviductal gene expression. The T4 treatment resulted in an increase in plasma concentration of T4; however, the T3 concentration was not affected. The long term administration of T4 had no effect on fertility; however, it resulted in a decreased sperm penetration rate and decreased the duration of fertility compared with the control group. The relative abundance of TGF-β4 and HSP70 mRNA in the SST was not influenced by T4 supplementation. The correlation coefficients between fertility and sperm penetration rate with relative abundance of TGF-β4 and HSP70 were not significant. Overall, among the diverse reproductive variable assessed in the current study, the sperm penetration rate and the duration of fertility were most responsive to long-term treatment with T4.

Triiodothyronine replacement in critically ill adults with non-thyroidal illness syndrome

Non-thyroidal illness syndrome is commonly encountered in critically ill patients, many of whom are treated with thyroid hormones despite uncertainty regarding their safety and effectiveness. This retrospective observational study sought to evaluate the utilization, safety, and effectiveness of triiodothyronine (T3) supplementation in critically ill adults admitted to either of two non-cardiac surgery mixed-medical/surgical intensive care units (ICU). Consecutive adults admitted to an ICU and treated with enterally administered T3 were identified over a two-year period. Data pertaining to demographics, T3 utilization, safety, and clinical outcomes were collected. Data were extracted from the medical records of 70 consecutive patients. All had baseline serum free T3 concentrations below the lower limit of our laboratory's reference range and 22 (31%) patients also had low thyroxine (T4) concentrations. The most commonly prescribed replacement doses were 25 and 50 µg for a median of seven days and almost half of the patients also received concomitant T4 supplementation. Serum thyroid hormones were available in 48 of 70 patients (69%) at a median [interquartile range (IQR)] of 7 [6-38] days. Normalization of free T3 serum concentrations occurred in 30 of 48 patients (63%) at a median [IQR] of 8 [7-33] days. A dose-response relationship was identifiable. New adverse events (atrial fibrillation/flutter, hypertension, sinus tachycardia, myocardial infarction) during therapy were less frequent than at baseline. This study suggests that with T3 supplementation there was evidence of serum free T3 normalization without evidence of associated harms. A definitive trial is needed to evaluate clinical effectiveness.

Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels.

Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels.

Inactivation of hepatic ATRX in Atrx Foxg1cre mice prevents reversal of aging-like phenotypes by thyroxine.

ATRX is an ATP-dependent chromatin remodeler required for the maintenance of genomic integrity. We previously reported that conditional Atrx ablation in the mouse embryonic forebrain and anterior pituitary using the Foxg1cre driver causes reduced health and lifespan. In these mice, premature aging-like phenotypes were accompanied by low circulating levels of insulin-like growth factor 1 (IGF-1) and thyroxine (T4), hormones that maintain stem cell pools and normal metabolic profiles, respectively. Based on emerging evidence that T4 stimulates expression of IGF-1 in pre-pubertal mice, we tested whether T4 supplementation in Atrx Foxg1cre mice could restore IGF-1 levels and ameliorate premature aging-like phenotypes. Despite restoration of normal serum T4 levels, we did not observe improvements in circulating IGF-1. In the liver, thyroid hormone target genes were differentially affected upon T4 treatment, with Igf1 and several other thyroid hormone responsive genes failing to recover normal expression levels. These findings hinted at Cre-mediated Atrx inactivation in the liver of Atrx Foxg1cre mice, which we confirmed. We conclude that the phenotypes observed in the Atrx Foxg1cre mice can be explained in part by a role of ATRX in the liver to promote T4-mediated Igf1 expression, thus explaining the inefficacy of T4 therapy observed in this study.

Thyroid Hormone Supplementation Restores Spatial Memory, Hippocampal Markers of Neuroinflammation, Plasticity-Related Signaling Molecules, and β-Amyloid Peptide Load in Hypothyroid Rats.

Hypothyroidism is a condition that becomes more prevalent with age. Patients with untreated hypothyroidism have consistently reported symptoms of severe cognitive impairments. In patients suffering hypothyroidism, thyroid hormone supplementation offers the prospect to alleviate the cognitive consequences of hypothyroidism; however, the therapeutic value of TH supplementation remains at present uncertain and the link between cellular modifications associated with hypothyroidism and neurodegeneration remains to be elucidated. In the present study, we therefore evaluated the molecular and behavioral consequences of T3 hormone replacement in an animal model of hypothyroidism. We have previously reported that the antithyroid molecule propylthiouracil (PTU) given in the drinking water favors cerebral atrophy, brain neuroinflammation, Aβ production, Tau hyperphosphorylation, and altered plasticity-related cell-signaling pathways in the hippocampus in association with hippocampal-dependent spatial memory deficits. In the present study, our aim was to explore, in this model, the effect of hippocampal T3 signaling normalization on various molecular mechanisms involved in learning and memory that goes awry under conditions of hypothyroidism and to evaluate its potential for recovery of hippocampal-dependent memory deficits. We report that T3 supplementation can alleviate hippocampal-dependent memory impairments displayed by hypothyroid rats and normalize key markers of thyroid status in the hippocampus, of neuroinflammation, Aβ production, and of cell-signaling pathways known to be involved in synaptic plasticity and memory function. Together, these findings suggest that normalization of hippocampal T3 signaling is sufficient to reverse molecular and cognitive dysfunctions associated with hypothyroidism.

Production and profitability of a beef herd on transitional Cymbopogon-Themeda veld receiving three levels of lick supplementation

The purpose of the study was to investigate the effects of three levels of lick supplementation on the production and reproduction of cows grazing transitional Cymbopogon-Themeda veld. The study was conducted over three years (2011–2014). A total of 150 Drakensberger cows were randomly allocated to three supplementary treatment groups. These supplementation formulations are available commercially and are typical of levels used under farming conditions. In summer Treatment 1 (T1) consisted of a supplement containing 50 g phosphate (P)/kg and 150 g crude protein (CP)/kg. T2 and T3 both consisted of supplements containing 60 g P/kg and 0 g CP/kg. In winter, T1 consisted of a supplement containing 367 g CP/kg, 77.5% non-protein nitrogen (NPN) and metabolizable energy (ME) content of 5.25 MJ/kg. T2 had 466 g CP/kg, 88.7% NPN and a ME content of 4.4 MJ/kg. T3 had 475 g CP/kg, 95.9% NPN and an ME content of 2.4 MJ/kg. Traits were calf birth weight, 100-day and weaning weights of calves, cow weight at weaning, inter-calving period (ICP), conception rate and body condition score (BCS) of cows. Calf birth weight was affected by supplementation treatment only in year 3 and 100-day weight in year 2. However, weaning weight and reproductive performance were not influenced by treatment. It was concluded that the level of supplementation of each treatment group enabled the cows to operate within their target weight range; however, it was more profitable to use the T3 supplementation option. Keywords: Cymbopogon-Themeda veld, cows, performance

Impact of supplementation of probiotic, prebiotic and synbiotic on serum biochemical profile of crossbred calves

A study was conducted on 24 fifteen day old crossbred calves that were divided into 4 groups of 6 calves each. The calves were fed different dietary treatments viz T0 (control group) - basal diet, T1 (probiotic group) - basal diet + Lactobacillus acidophilus @ 1 g/calf/day (2 x 1010 cfu/ g), T2 (prebiotic group)- basal diet + Mannan oligosaccharide (MOS) @ 4 g per calf/day and T3 (synbiotic group) basal diet + Lactobacillus acidophilus @ 0.5 gm (2 x 1010 cfu/ g) + 2 g MOS per calf/day respectively for a period of 90 days. Blood samples were taken at monthly interval and serum was separated to estimate different biochemical parameters. The results of study indicated that probiotic (Lactobacillus acidophilus), prebiotic (MOS) and synbiotic supplementation were effective in reduction of serum cholesterol and triglycerides at 60th and 90th day. Serum creatinine, glucose, urea and bilirubin were unaffected by dietary supplementation of probiotic, prebiotic (MOS) and synbiotic. There was no effect of T1, T2 and T3 supplementation on Serum enzymes, Aspartate aminotransferase (AST) and Alanine Amino Transferase (ALT).

Effect of zinc oxide and zinc oxide nano particles on performance, carcass characteristics and metallotheionine (MTmRNA) expression in broiler chicken

The present study was conducted to evaluate the effect of supplementation of zinc oxide and zinc oxide nanoparticles (ZnO NPs) on performance, carcass characteristics, concentration of Zn in tibia and serum and metallothionein (MT) mRNA expression on different organs in commercial broiler chicken. A total of120 day-old broiler chickens were assigned to 4 dietary treatments with 3 replicate and 10 broiler chicken per replicate. Dietary treatment includes T1 (Basal diet without Zn), T2 and T3 supplementation of basal diet (BD) with 40 and 80 mg/kg of zinc oxide and the last T4 supplementation of ZnO NPs at 20 mg/kg, respectively. The study lasted for 42 days. Lower as only one dose of ZnO NPs supplementation up to 20 mg/kg did not affect the growth performance which was comparable with Zn oxide treatment groups. Carcass traits remained comparable to all other treatment groups. Meanwhile, it was noticed that supplementation of Zn either in oxide or in Nanoparticles had a significantly higher concentration of Zn in tibia and serum. ZnO NPs at 20 mg/kg showed the increased MT mRNA expression in all the organs. Hence, the present study indicated that dietary Zn supplementation could be reduced up to 20 mg/kg when supplemented as ZnO NPs without affecting growth performance and carcass traits.

Legume Wafer Supplementation to Increase the Performance of Post-Weaning Ettawa Grade Goats

This research was conducted to analyze the effect of legume wafer supplementation on the performance of post weaning Ettawa Grade goats. A total of 16 post weaning Ettawa Grade goats (average body weight 13.10±0.91 kg) were grouped into 4 group treatments and 4 blocks as replicate in a completely randomized block design. The treatments were T0 (basal diet/control), T1 (supplementation of 12.12% wafer supplement of Indigofera zollingeriana), T2 (supplementation of 13.54% wafer supplement of Leucaena leucocephala) and T3 (supplementation of 12.37% wafer supplement of Calliandra calothyrsus). The feed intake, nutrient digestibility, average daily gain (ADG), feed efficiency (FE), and income over feed cost (IOFC) were observed. The results showed that supplementation of legume wafer increased (P<0.05) the feed intake, organic matter digestibility, ADG, FE, and IOFC. Supplementation of I. zollingeriana wafer increased ADG by 55.08%, FE by 34.91%, and IOFC by 14.53%; L. leucocephala wafer increased ADG by 66.18%, FE by 41.63%, and IOFC by 19.09%; and C. calothyrsus wafer increased ADG by 32.62%, FE by 11.30%, and IOFC by 14.34%. In conclusion, the addition of legume wafer supplements into the rations could increase the feed utility value of legumes and L. leucocephala wafer at 13.54% showed the best performance in post-weaning Ettawa Grade goats.

Oral Triiodothyronine for Infants and Children Undergoing Cardiopulmonary Bypass

This study evaluated the efficacy and safety of oral triiodothyronine (T3; Tetronine, Dalim BioTech, Korea) for infants and children undergoing cardiopulmonary bypass in an Indonesian population. We performed a single-center, randomized, double-blind, and placebo-controlled trial in children aged 3 years and younger undergoing congenital heart disease operations with cardiopulmonary bypass. We administered oral T3 (1 μg/kg per body weight/dose) or placebo (saccharum lactis) by nasogastric tube every 6 hours for 60 hours after induction of anesthesia. The primary end point, time to extubation, was compared with Cox regression. The modified intention-to-treat group included 101 placebo and 104 treated patients. The stratified log-rank test did not show a significant treatment difference (p= 0.061) for time to extubation, but after adjustment for age, the nutritional Z score, and Aristotle surgical complexity, the hazard ratio was 1.33 (95% confidence interval, 1.00 to 1.76; p= 0.049). The effect of T3 was stronger in the strata aged 5 months and younger (hazard ratio, 1.86; 95% confidence interval 1.02 to 3.39; p= 0.043). Median intubation time was 47.3 hours for the placebo and 32.1 hours for the T3 group in aged 5 months and younger. Adverse events rates, including arrhythmia, were similar between groups, although sepsis was more frequent with placebo. Oral T3 supplementation may shorten time to extubation in children undergoing congenital heart disease operations, particularly infants aged 5 months or younger. Administration is relatively safe, simple and inexpensive.

Combined supplementation of ascorbic acid and thyroid hormone T3 affects tenocyte proliferation. The effect of ascorbic acid in the production of nitric oxide.

Tissue engineering is now increasingly focusing on cell-based treatments as promising tools to improve tendon repair. However, many crucial aspects of tendon biology remain to be understood before adopting the best experimental approach for cell-tissue engineering. The role played by Ascorbic Acid (AA) alone and in combination with thyroid hormone T3 in the viability and proliferation of primary human tendon-derived cells was investigated. Human tenocyte viability was detected by Trypan blue exclusion test and cellular proliferation rate was evaluated by CFSE CellTrace™. In addition, the potential role of the AA in the production of Nitric Oxide (NO) was also examined. In this in vitro model, an increase in tenocyte proliferation rate was observed as a consequence of progressively increased concentrations of AA (from 10 to 50 µg/ml). The addition of the T3 hormone to the culture further increased tenocyte proliferation rate. In detail, the most evident effect on cellular growth was achieved using the combined supplementation of 50 µg/ml AA and 10-7 M T3. We showed that the highest concentration of AA (100 and 500 µg/ml) caused cytotoxicity to human tenocytes. Moreover, it was shown that AA reduces NO synthesis. These results show that AA is a cell proliferation inducer that triggers tenocyte growth, while it reduces NO synthesis.