BACKGROUND Thyroxine-binding globulin(TBG;the gene product of SERPINA7)is the main transporter of thyroid hormones in humans.Mutations in the TBG gene may lead to inherited TBG deficiency.There have been 28 reported m...BACKGROUND Thyroxine-binding globulin(TBG;the gene product of SERPINA7)is the main transporter of thyroid hormones in humans.Mutations in the TBG gene may lead to inherited TBG deficiency.There have been 28 reported mutations that associate with complete TBG deficiency(TBG-CD).Here we identified a novel frameshift mutation causing early termination of the TBG protein and TBG-CD in a Chinese family.CASE SUMMARY A 46-year-old Chinese man was referred to our hospital with normal free thyroxine,free triiodothyronine,thyrotropin,but lower total thyroxine and total triiodothyronine,and undetectable serum TBG,indicative of TBG-CD.Blood samples were obtained from the patient’s family members and thyroid function and serum TBG were evaluated.Genomic DNA from peripheral blood was sequenced to detect possible TBG mutation(s).Quantitative PCR high-resolution melting curve analysis was used to screen TBG-Poly(L283F)among 117 Chinese men.A novel mutation of TBG(p.Phe135Alafs*21),a 19-nucleotide insertion in exon 1,was identified,which resulted in a truncated TBG protein product and caused TBG-CD.The other mutation,identified in the proband’s father,is a known polymorphism,TBG-Poly(L283F).The frequency of the TBG-Poly allele among 117 unrelated Han Chinese men from northeast China was 21.37%.CONCLUSION A novel mutation in the TBG gene associated with the TBG-CD phenotype was identified in a Chinese family.Additionally,it was found that 21.37%of Chinese males had TBG-Poly(L283F).展开更多
Objectives To evaluate the effect of thyroid hormone therapy with low dose of thyroxin on cardiac function in elderly patients with heart failure and sick euthyroid syndrome. Methods Forty-seven patients (33 males and...Objectives To evaluate the effect of thyroid hormone therapy with low dose of thyroxin on cardiac function in elderly patients with heart failure and sick euthyroid syndrome. Methods Forty-seven patients (33 males and 14 females, mean age 85.9+4.6 years,ranging from 80 to 99 years) with chronic heart failure (NYHA Ⅱ-Ⅳ) and low triiodothyronine (T3) state were randomly allocated to the treatment group or control group. The treatment group patients received oral administration of levothyroxine sodium (Euthyrox) 25-50mg/d in addition to conventional therapy of heart failure, whereas patients in control group were given conventional therapy only. Serum level of total T3 (TT3), free T3 (FT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were determined. For both groups, left ventricular ejection fraction (LVEF) and stroke volume (SV) were assessed by two-dimensional echocardiography before and at 8 weeks after treatment. The changes of these parameters after the treatment were evaluated by adjusting heart rate in the two groups. Results The reduced serum T3 level in the treatment group was corrected after thyroid hormone therapy,and these patients had a significant improvement in cardiac function after treatment. By contrast, in the control group only changes of serum TT3 and TT4 levels and SV and LVEF after treatment were statistically significant. The heart rate-adjusted mean SV and LVEF in both groups were also increased, which was significantly greater in the treatment group than in the control group. Conclusion In the elderly patients with heart failure and sick euthyroid syndrome, addition of thyroxine at a low dosage to the conventional treatment could effectively improve the low T3 state and cardiac function independent of changes of heart rate.展开更多
Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and n...Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.展开更多
Introduction: Down syndrome (DS) is the most common chromosomal abnormality causing mental handicap in humans. Children with DS have significant medical problems and developmental delay which are further impaired by h...Introduction: Down syndrome (DS) is the most common chromosomal abnormality causing mental handicap in humans. Children with DS have significant medical problems and developmental delay which are further impaired by hypothyroidism. Those clinical features are potentially improved by using thyroxine replacement therapy. Objectives: To examine the evidence of effectiveness (motor & mental development) and safety of thyroxine supplementation in the treatment of SH and CH in children with DS. Methods: Several medical data bases (MEDLINE, EMBASE, CINAHL, Cochrane, Clinical Trials Gov, Essential Evidence and Google) were searched until 20 October, 2011, for randomized control trials (RCTs) that had examined thyroxine’s effectiveness and safety in the treatment of SH or CH in children with DS. Results: There were two high quality RCTs that examined thyroxine in the treatment of CH in children with DS, and no RCTs were found to have examined the effectiveness of thyroxine for SH in children with DS. Conclusion: The RCT which met our inclusion criteria provides the reliable evidence in recommending thyroxine for the treatment of CH in children with DS which is similar to the guidelines for general population. The absence of RCTs examining the treatment of SH in Children with DS indicates the need to conduct such trials.展开更多
The present study deals with the effect of exogenous treatment of O. niloticus females with L-thyroxine (T4) on the development of the digestive system during larval rearing, and its subsequent effect on larval growth...The present study deals with the effect of exogenous treatment of O. niloticus females with L-thyroxine (T4) on the development of the digestive system during larval rearing, and its subsequent effect on larval growth and survival. The development of the digestive tract and accessory glands was investigated histologically and histochemically in the developing O. niloticus larvae, from control and T4-treated spawners. During yolk-sac absorption, the digestive system of the fish underwent further differentiation and the rudimentary alimentary canal became segmented into four different histological regions: the buccopharynx, oesophagus, stomach and intestine. The injection of females O. niloticus with thyroxine (1 or 10 μg T4/g BW) greatly enhanced the development of the digestive tract and accessory glands of larvae as indicated by the quantitative and qualitative changes of the mucus composition from predominantly neutral to a mixture of neutral and acid mucosubstances, or acid mucosubstances occurred during the rearing period for the larvae produced from T4-treated females. This may be due to the direct effect of exogenous thyroxine, which might have been transferred from maternal circulation into the oocytes and larvae, on the synthesis of proteins, which increased with larval development. Thus, thyroxine directly or indirectly improved O. niloticus larval growth, since a marked increase in both, length and weight of larvae occurred during the experimental period. In addition, larvae from treated females also gave a significantly higher survival rate than that of control. It could be concluded that exogenous T4 in maternal circulation might have been transferred into oocytes and larvae. The transferred thyroid hormone appears to play some role in the early development of larvae and may confer a distinct advantage for the growth of the offspring of the Nile tilapia, O. niloticus.展开更多
The effects of recombinant eel growth hormone (reGH).methyltestosterone (MT)and L-thyroxine (T4)on the growth of red sea bream. Pagrosomus major.were investigated.Administration of reGH to fry by immersion at 2 mg 1 f...The effects of recombinant eel growth hormone (reGH).methyltestosterone (MT)and L-thyroxine (T4)on the growth of red sea bream. Pagrosomus major.were investigated.Administration of reGH to fry by immersion at 2 mg 1 for 2 hevery 5 dsys resulted in significant increase in both weight and length.but the condition factor (CF) diminished relative to that of similarly treated controls over the 37day treatment period.Immersion in 0.1 mg:1 T4 also resulted in significant increase in both weight and length and higher survival rate of test fry compared to the controls. Immersion in MT had less effect on growth and high-dose resulted in high mortality.In the second study.injection of 2 μg reGH(gwk)caused a significant increase in the specific growth rate (SGR) of test red sea bream fingerlings relative to that of the controls during the 4-week treatment period and maintained the increasing trend over the post-treatment period (weeks 4-6).Injection of MT at a dosage of 1μg (gwk) resulted in a significant展开更多
The larvae of ascidian Styela canopus Savigny were treated with epinephrine, norepinephrine, L-DOPA, GABA and thyroxin to test the ability of these compounds to induce or inhibit larval settlement and metamorphosis. T...The larvae of ascidian Styela canopus Savigny were treated with epinephrine, norepinephrine, L-DOPA, GABA and thyroxin to test the ability of these compounds to induce or inhibit larval settlement and metamorphosis. The results showed that epinephrine, norepinephrine and L-DOPA at the concentration of 1μmol/dm 3 induced larval settlement and metamorphosis in S. canopus, with short exposure (1 h) to 1 μmol/dm 3 of L-DOPA inducing rapid settlement. In contrast, GABA at the concentrations of 0.1 ～100.0 μmol/dm 3 significantly inhibited the settlement and metamorphosis of S. canopus larvae. In addition, thyroxin at 1～50 μg/dm 3 had no effect on larval settlement and metamorphosis in S. canopus. These results suggest the importance of neurotransmitters in the settlement and metamorphosis of S. canopus larvae.展开更多
A Capillary electrophortic enzyme linked immunoassay with electrochemical detection (CE-EIA-ED) has been developed. The method can be used to determine thyroxine with a limit of 3.8×10-9 mol/L.
The effects of thyroxine and atropine in ameliorating phosphamidon intoxication in chick embryos was studied. Treatment of phosphamidon significantly enhanced the moriality and abnormalityrates, decreased the average ...The effects of thyroxine and atropine in ameliorating phosphamidon intoxication in chick embryos was studied. Treatment of phosphamidon significantly enhanced the moriality and abnormalityrates, decreased the average body weights, and cholinesterase activity in chick embryos. When thyroxine was administered to the phosphamidon intoxicated embryos, the above parameters changedsignificantly, indicating an ameliorating effect of thyroxine against phosphamidon intoxication in chick embryos. The combined thyroxine and atropine therapy did not further improve the ameliorating effect. Since in many respects chick embryo development parallels that of mammalian embryos,a short-term use of thyroxine as a protective agent against organophosphate toxicity might be展开更多
Bisphenol A (BPA) is a chemical with high production volume and wide applications in many industries.Although BPA is known as an endocrine disruptor,its toxic mechanisms have not been fully characterized.Due to its st...Bisphenol A (BPA) is a chemical with high production volume and wide applications in many industries.Although BPA is known as an endocrine disruptor,its toxic mechanisms have not been fully characterized.Due to its structural similarity to thyroid hormones thyroxine (T4) and triiodothyronine (T3),one possible mechanism of BPA toxicity is disruption of hormone transport by competitive binding with the transport proteins.In this study,the binding interactions of BPA,T4,and T3 with three thyroid hormone transport proteins,human serum albumin (HSA),transthyretin (TTR),and thyroxine-binding globulin (TBG) were investigated by fluorescence measurement.Using two site-specific fluorescence probes dansylamide and dansyl-L-proline,the binding constants of BPA with HSA at drug site I and site II were determined as 2.90 × 10 4 and 3.14 × 10 4 L/mol,respectively.By monitoring the intrinsic fluorescence of tryptophan,a binding constant of 4.70 × 10 3 L/mol was obtained.Similarly,by employing 8-anilino-1-naphthalenesulfonic acid as fluorescence probe,the binding affinity of BPA with TTR and TBG was measured to be 3.10 × 10 5 and 5.90 × 10 5 L/mol,respectively.In general,BPA showed lower binding affinity with the proteins than T3 did,and even lower affinity than T4.Using these binding constants,the amount of BPA which would bind to the transport proteins in human plasma was estimated.These results suggest that the concentrations of BPA commonly found in human plasma are probably not high enough to interfere with T4 transport.展开更多
基金Supported by the National Natural Science Foundation of China,No.81570711National Clinical Key College Fund and the Key Platform Foundation of Science and Technology for the Universities in Liaoning Province,No.16010
文摘BACKGROUND Thyroxine-binding globulin(TBG;the gene product of SERPINA7)is the main transporter of thyroid hormones in humans.Mutations in the TBG gene may lead to inherited TBG deficiency.There have been 28 reported mutations that associate with complete TBG deficiency(TBG-CD).Here we identified a novel frameshift mutation causing early termination of the TBG protein and TBG-CD in a Chinese family.CASE SUMMARY A 46-year-old Chinese man was referred to our hospital with normal free thyroxine,free triiodothyronine,thyrotropin,but lower total thyroxine and total triiodothyronine,and undetectable serum TBG,indicative of TBG-CD.Blood samples were obtained from the patient’s family members and thyroid function and serum TBG were evaluated.Genomic DNA from peripheral blood was sequenced to detect possible TBG mutation(s).Quantitative PCR high-resolution melting curve analysis was used to screen TBG-Poly(L283F)among 117 Chinese men.A novel mutation of TBG(p.Phe135Alafs*21),a 19-nucleotide insertion in exon 1,was identified,which resulted in a truncated TBG protein product and caused TBG-CD.The other mutation,identified in the proband’s father,is a known polymorphism,TBG-Poly(L283F).The frequency of the TBG-Poly allele among 117 unrelated Han Chinese men from northeast China was 21.37%.CONCLUSION A novel mutation in the TBG gene associated with the TBG-CD phenotype was identified in a Chinese family.Additionally,it was found that 21.37%of Chinese males had TBG-Poly(L283F).
文摘Objectives To evaluate the effect of thyroid hormone therapy with low dose of thyroxin on cardiac function in elderly patients with heart failure and sick euthyroid syndrome. Methods Forty-seven patients (33 males and 14 females, mean age 85.9+4.6 years,ranging from 80 to 99 years) with chronic heart failure (NYHA Ⅱ-Ⅳ) and low triiodothyronine (T3) state were randomly allocated to the treatment group or control group. The treatment group patients received oral administration of levothyroxine sodium (Euthyrox) 25-50mg/d in addition to conventional therapy of heart failure, whereas patients in control group were given conventional therapy only. Serum level of total T3 (TT3), free T3 (FT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were determined. For both groups, left ventricular ejection fraction (LVEF) and stroke volume (SV) were assessed by two-dimensional echocardiography before and at 8 weeks after treatment. The changes of these parameters after the treatment were evaluated by adjusting heart rate in the two groups. Results The reduced serum T3 level in the treatment group was corrected after thyroid hormone therapy,and these patients had a significant improvement in cardiac function after treatment. By contrast, in the control group only changes of serum TT3 and TT4 levels and SV and LVEF after treatment were statistically significant. The heart rate-adjusted mean SV and LVEF in both groups were also increased, which was significantly greater in the treatment group than in the control group. Conclusion In the elderly patients with heart failure and sick euthyroid syndrome, addition of thyroxine at a low dosage to the conventional treatment could effectively improve the low T3 state and cardiac function independent of changes of heart rate.
基金grants from the National Natural Science Foundation of China(No.81270885,No.81570726 and No.81600609)Shanghai Jiao Tong University School of Medicine(2014)+4 种基金the Ministry of Science and Technology in China(No.2012CB524906)the Science and Technology Commission of Shanghai Municipality(No.14495810700 and No.16410723200)Three-year Action Plan for Public Health System Construction in Shanghai by Shanghai Municipal Commission of Health and Family Planning(2015-2017)Clinical Potential Subject Construction of Shanghai Jiao Tong University School of Medicine(2014),Shanghai Municipal Health Bureau of China(No.20124262)Seed Founding of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine(No.JYZZ032).
文摘Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.
文摘Introduction: Down syndrome (DS) is the most common chromosomal abnormality causing mental handicap in humans. Children with DS have significant medical problems and developmental delay which are further impaired by hypothyroidism. Those clinical features are potentially improved by using thyroxine replacement therapy. Objectives: To examine the evidence of effectiveness (motor & mental development) and safety of thyroxine supplementation in the treatment of SH and CH in children with DS. Methods: Several medical data bases (MEDLINE, EMBASE, CINAHL, Cochrane, Clinical Trials Gov, Essential Evidence and Google) were searched until 20 October, 2011, for randomized control trials (RCTs) that had examined thyroxine’s effectiveness and safety in the treatment of SH or CH in children with DS. Results: There were two high quality RCTs that examined thyroxine in the treatment of CH in children with DS, and no RCTs were found to have examined the effectiveness of thyroxine for SH in children with DS. Conclusion: The RCT which met our inclusion criteria provides the reliable evidence in recommending thyroxine for the treatment of CH in children with DS which is similar to the guidelines for general population. The absence of RCTs examining the treatment of SH in Children with DS indicates the need to conduct such trials.
文摘The present study deals with the effect of exogenous treatment of O. niloticus females with L-thyroxine (T4) on the development of the digestive system during larval rearing, and its subsequent effect on larval growth and survival. The development of the digestive tract and accessory glands was investigated histologically and histochemically in the developing O. niloticus larvae, from control and T4-treated spawners. During yolk-sac absorption, the digestive system of the fish underwent further differentiation and the rudimentary alimentary canal became segmented into four different histological regions: the buccopharynx, oesophagus, stomach and intestine. The injection of females O. niloticus with thyroxine (1 or 10 μg T4/g BW) greatly enhanced the development of the digestive tract and accessory glands of larvae as indicated by the quantitative and qualitative changes of the mucus composition from predominantly neutral to a mixture of neutral and acid mucosubstances, or acid mucosubstances occurred during the rearing period for the larvae produced from T4-treated females. This may be due to the direct effect of exogenous thyroxine, which might have been transferred from maternal circulation into the oocytes and larvae, on the synthesis of proteins, which increased with larval development. Thus, thyroxine directly or indirectly improved O. niloticus larval growth, since a marked increase in both, length and weight of larvae occurred during the experimental period. In addition, larvae from treated females also gave a significantly higher survival rate than that of control. It could be concluded that exogenous T4 in maternal circulation might have been transferred into oocytes and larvae. The transferred thyroid hormone appears to play some role in the early development of larvae and may confer a distinct advantage for the growth of the offspring of the Nile tilapia, O. niloticus.
文摘The effects of recombinant eel growth hormone (reGH).methyltestosterone (MT)and L-thyroxine (T4)on the growth of red sea bream. Pagrosomus major.were investigated.Administration of reGH to fry by immersion at 2 mg 1 for 2 hevery 5 dsys resulted in significant increase in both weight and length.but the condition factor (CF) diminished relative to that of similarly treated controls over the 37day treatment period.Immersion in 0.1 mg:1 T4 also resulted in significant increase in both weight and length and higher survival rate of test fry compared to the controls. Immersion in MT had less effect on growth and high-dose resulted in high mortality.In the second study.injection of 2 μg reGH(gwk)caused a significant increase in the specific growth rate (SGR) of test red sea bream fingerlings relative to that of the controls during the 4-week treatment period and maintained the increasing trend over the post-treatment period (weeks 4-6).Injection of MT at a dosage of 1μg (gwk) resulted in a significant
基金This research was supported by the National Natural Science Foundation of China under contract Nos 40276041 and 49976034.
文摘The larvae of ascidian Styela canopus Savigny were treated with epinephrine, norepinephrine, L-DOPA, GABA and thyroxin to test the ability of these compounds to induce or inhibit larval settlement and metamorphosis. The results showed that epinephrine, norepinephrine and L-DOPA at the concentration of 1μmol/dm 3 induced larval settlement and metamorphosis in S. canopus, with short exposure (1 h) to 1 μmol/dm 3 of L-DOPA inducing rapid settlement. In contrast, GABA at the concentrations of 0.1 ～100.0 μmol/dm 3 significantly inhibited the settlement and metamorphosis of S. canopus larvae. In addition, thyroxin at 1～50 μg/dm 3 had no effect on larval settlement and metamorphosis in S. canopus. These results suggest the importance of neurotransmitters in the settlement and metamorphosis of S. canopus larvae.
基金supported by the National Natural Science Foundation of Chinathe Natural Science Foundation of Shandong Provincethe Key State Laboratory of Electroanalytical Chemistry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences
文摘A Capillary electrophortic enzyme linked immunoassay with electrochemical detection (CE-EIA-ED) has been developed. The method can be used to determine thyroxine with a limit of 3.8×10-9 mol/L.
文摘The effects of thyroxine and atropine in ameliorating phosphamidon intoxication in chick embryos was studied. Treatment of phosphamidon significantly enhanced the moriality and abnormalityrates, decreased the average body weights, and cholinesterase activity in chick embryos. When thyroxine was administered to the phosphamidon intoxicated embryos, the above parameters changedsignificantly, indicating an ameliorating effect of thyroxine against phosphamidon intoxication in chick embryos. The combined thyroxine and atropine therapy did not further improve the ameliorating effect. Since in many respects chick embryo development parallels that of mammalian embryos,a short-term use of thyroxine as a protective agent against organophosphate toxicity might be
基金supported by the National Natural Science Foundation of China(No. 20890112,20921063,20825519)
文摘Bisphenol A (BPA) is a chemical with high production volume and wide applications in many industries.Although BPA is known as an endocrine disruptor,its toxic mechanisms have not been fully characterized.Due to its structural similarity to thyroid hormones thyroxine (T4) and triiodothyronine (T3),one possible mechanism of BPA toxicity is disruption of hormone transport by competitive binding with the transport proteins.In this study,the binding interactions of BPA,T4,and T3 with three thyroid hormone transport proteins,human serum albumin (HSA),transthyretin (TTR),and thyroxine-binding globulin (TBG) were investigated by fluorescence measurement.Using two site-specific fluorescence probes dansylamide and dansyl-L-proline,the binding constants of BPA with HSA at drug site I and site II were determined as 2.90 × 10 4 and 3.14 × 10 4 L/mol,respectively.By monitoring the intrinsic fluorescence of tryptophan,a binding constant of 4.70 × 10 3 L/mol was obtained.Similarly,by employing 8-anilino-1-naphthalenesulfonic acid as fluorescence probe,the binding affinity of BPA with TTR and TBG was measured to be 3.10 × 10 5 and 5.90 × 10 5 L/mol,respectively.In general,BPA showed lower binding affinity with the proteins than T3 did,and even lower affinity than T4.Using these binding constants,the amount of BPA which would bind to the transport proteins in human plasma was estimated.These results suggest that the concentrations of BPA commonly found in human plasma are probably not high enough to interfere with T4 transport.
