EFFECTS OF AMIODARONE ON THYROID IODINE METABOLISM IN VITRO1)

1977 ◽  
Vol 85 (4) ◽  
pp. 781-790 ◽  
Author(s):  
Bernardo E. Gluzman ◽  
Aldo H. Coleoni ◽  
Héctor M. Targovnik ◽  
Hugo Niepomniszcze
Keyword(s):  
Thyroid Gland ◽  
Direct Action ◽  
The Other ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Iodide Transport ◽  
Iodine Metabolism ◽  
Per Se ◽  
Rule Out

ABSTRACT Since alterations of thyroid function have been reported in patients treated with amiodarone, 2-butyl,3-(4-diethylaminoethoxy-3,5- diiodo, benzoyl) benzofuran, the effects of this drug on the active iodide transport, organic iodine formation, thyroid peroxidase and the enzymatic iodotyrosine deiodination, were studied. In pig thyroid slices the iodide transport was affected by amiodarone at concentrations of 10−4 m and 10−5 M, showing a decrease of T/M (tissue/medium) ratios of 20% and 23%, respectively. Lower concentrations produced no significant differences from the controls. Iodotyrosine synthesis was only, but poorly, affected by 10−4 m and 10−5 m amiodarone. Inhibition of the DIT formation was greater than that produced for MIT. Thyroid peroxidase activity, as measured by the tyrosine-iodinase assay, showed a 20% decrease at 10−3 m amiodarone. None of the other concentrations have affected the activity of the enzyme, except for 7% at a concentration of 10−4 m. The iodotyrosine deiodination was affected by amiodarone only at a concentration of 10−3 m and 10−4 m. The inhibitions were of 22.5% and 16.8%, respectively. We have concluded that, under the conditions of our study, amiodarone per se does not affect the intrathyroidal iodine metabolism in concentrations which are usually present in the sera of patients treated with this drug. However, it is not possible to rule out an in vivo direct action, if amiodarone is substantially concentrated in the human thyroid gland.

Effects of phenylbutazone on thyroid iodine metabolism in vitro

1980 ◽  
Vol 94 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Héctor M. Targovnik ◽  
Bernardo E. Gluzman ◽  
Aldo H. Coleoni ◽  
Hugo Niepomniszcze
Keyword(s):  
Thyroid Function ◽  
Peroxidase Activity ◽  
Thyroid Peroxidase ◽  
Soluble Enzyme ◽  
Iodide Transport ◽  
Significant Difference ◽  
Soluble Peroxidase ◽  
Iodine Metabolism ◽  
Bovine Thyroid

Abstract. Several alterations of thyroid function parameters have been reported in patients treated with phenylbutazone and we have studied the effect of this drug on the intrathyroidal iodine metabolism. An inhibition of the iodide transport expressed in terms of T/M ratios was observed in bovine thyroid slices incubated with high phenylbutazone concentrations. 10−3m produced 72% inhibition whereas lower concentrations showed no significant difference as compared with controls. Iodotyrosine synthesis was affected by 10−4m and 10−5m phenylbutazone. Formation of iodothyronine synthesis was markedly affected between 10−4m and 10−7m phenylbutazone concentrations. Thyroid peroxidase activity was measured by tyrosine-iodinase, triiodide and guaiacol assays. Soluble, pseudosolubilized and crude peroxidase preparations from bovine glands, as well as the soluble enzyme from human thyroids, have shown inhibition of tyrosine-iodinase activity when incubated with phenylbutazone in concentrations ranging from 10−3m to 10−8m, with a Ki of 4 × 10−6m for bovine thyroid peroxidase and of 6 × 10−6m for human soluble peroxidase. Formation of triiodide was affected between 10−3m and 10−8m phenylbutazone concentrations. Guaiacol peroxidation was scarcely affected by the action of the drug. We have concluded that phenylbutazone affects the intrathyroidal iodine metabolism through the inhibition of thyroid peroxidase in concentrations which are usually present in the sera of patients treated with this drug.

EVIDENCE THAT BOTH LONG-ACTING THYROID STIMULATOR AND LONG-ACTING THYROID STIMULATOR-PROTECTOR STIMULATE THE HUMAN THYROID GLAND

1979 ◽  
Vol 80 (2) ◽  
pp. 215-221 ◽  
Author(s):  
S. D. HOLMES ◽  
S. M. DIRMIKIS ◽  
T. J. MARTIN ◽  
D. S. MUNRO
Keyword(s):  
Thyroid Gland ◽  
Cyclic Amp ◽  
Immunoglobulin G ◽  
The Other ◽  
Human Thyroid ◽  
Thyroid Stimulating Immunoglobulins ◽  
Long Acting ◽  
Mouse Thyroid

Thyroid-stimulating immunoglobulins were prepared from two potent sera, one contained long-acting thyroid stimulator (LATS) and the other contained both LATS and LATS-protector (LATS-P). The potencies of the immunoglobulin G (IgG) preparations were estimated in the McKenzie assay. The accumulation of cyclic AMP in mouse thyroid lobes was stimulated only by LATS–IgG; LATS-P–IgG was inactive. In contrast, both LATS–IgG and LATS-P–IgG were equally effective in slices of human thyroid.

Effect of hypophysectomy by partial decapitation and treatment with thiourea on iodine metabolism in the developing chick embryo

1983 ◽  
Vol 98 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Nicole Daugèras-Bernard ◽  
François Lachiver
Keyword(s):  
Thyroid Gland ◽  
Chick Embryo ◽  
Pituitary Gland ◽  
Direct Action ◽  
Thyroid Stimulating Hormone ◽  
Yolk Sac ◽  
Pituitary Hormone ◽  
Iodine Metabolism ◽  
Tsh Secretion ◽  
And Control

The hypothesis of an action of the pituitary gland of the developing chick embryo in the transfer of iodide from the yolk of the egg to the circulation of the embryo, through the yolk sac, was tested. Plasma iodide levels and thyroidal iodine contents were determined in hypophysectomized (by partial decapitation), thiourea-injected and control embryos. From day 11 of incubation these parameters were always lower in the 'hypophysectomized' embryos than in controls, and plasma iodide levels of the thiourea-treated embryos were higher than those of controls. These results indicate a reduced iodide transfer from the yolk to the 'hypophysectomized' embryo, and an increased iodide transfer to the thioureatreated embryo. This occurred in spite of a reduced thyroid hormonal secretion in both series. The pituitary gland could therefore have a direct action (not through the thyroid gland) at the yolk sac level, to augment the transfer of iodide from the yolk in intact embryos from day 11 to the end of incubation. Thyroid-stimulating hormone (TSH) could be the pituitary hormone acting at the yolk sac level, the increased iodide transfer observed in the thiourea-injected embryos being due to a raised TSH secretion responding to the decreased plasma thyroxine levels.

Effects of Carbohydrate Pulses and pH on Population Shifts within Oral Microbial Communities in vitro

1989 ◽  
Vol 68 (9) ◽  
pp. 1298-1302 ◽  
Author(s):  
D.J. Bradshaw ◽  
A.S. McKee ◽  
P.D. Marsh
Keyword(s):  
Microbial Communities ◽  
Carbohydrate Metabolism ◽  
Oral Bacteria ◽  
The Other ◽  
Carbohydrate Availability ◽  
Oral Microflora ◽  
End Products ◽  
Per Se

A mixed culture chemostat system was used to distinguish between the effects of carbohydrate availability per se and the low pH generated from carbohydrate metabolism on the proportions of bacteria within microbial communities. Nine oral bacteria were grown at pH 7 and pulsed with glucose on ten consecutive days. In one chemostat, the pH was maintained automatically at 7 throughout the experimental period, while in the other, pH control was discontinued for six hours after each pulse. Glucose pulses at neutral pH had little effect on the composition of the microflora. Only the proportions of A. viscosus and V. dispar increased; L. casei and S. mutans remained at low levels (0.2% and 1.0%, respectively). Acetate and propionate were the predominant end-products of metabolism; lactate levels were low. In contrast, when pH was allowed to fall after each glucose pulse, the composition of the microflora altered dramatically. The amounts of L. casei and S. mutans increased both as a proportion of the total count and in absolute numbers, as did V. dispar, whereas the amounts of the other Gram-negative organisms (B. intermedius, F. nucleatum, and N. subflava) and S. sanguis were considerably reduced. Lactate formed a major portion of the metabolic end-products. Successive glucose pulses resulted in both amplified changes in the microflora and a steadily greater rate and final extent of acid production. This is in agreement with the reported shifts in the oral microflora in vivo in response to frequent carbohydrate intake. Analysis of the data strongly suggests that the pH generated from carbohydrate metabolism, rather than carbohydrate availability per se, is responsible for the widely reported shifts in composition and metabolism of the oral microflora in vivo.

Validation of Immunohistochemistry for Canine Proteins Involved in Thyroid Iodine Uptake and Their Expression in Canine Follicular Cell Thyroid Carcinomas (FTCs) and FTC-Derived Organoids

2021 ◽  
pp. 030098582110188
Author(s):  
Jana Jankovic ◽  
Martina Dettwiler ◽  
Martin González Fernández ◽  
Eve Tièche ◽  
Kerstin Hahn ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Western Blot ◽  
Follicular Cell ◽  
Iodine Uptake ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Thyroid Cell ◽  
Follicular Cells ◽  
Thyroid Cells ◽  
Primary Tumors

Thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, and thyroid peroxidase (TPO) are essential for the uptake of iodine by follicular thyroid cells. The aim of this study was to establish immunohistochemistry (IHC) protocols for TSHR, NIS, pendrin, and TPO in canine tissues and characterize their expression in organoids derived from canine follicular cell thyroid carcinoma (FTC) and in the respective primary tumors. This constitutes a fundamental step to establish organoids as a model to study the uptake of iodine in canine FTC. Commercially available antibodies directed against human proteins were selected. Antibody specificity was confirmed by western blot using lysates of the HTori-3 human thyroid cell line and healthy canine thyroid gland. IHC was validated using HTori-3 cells and a set of canine normal tissues including healthy thyroid gland. The expression of TSHR, NIS, pendrin, and TPO was evaluated in 3 organoid lines derived from FTC and respective primary tumors. All 4 antibodies produced specific bands by western blot and cytoplasmic labeling in follicular cells by IHC in both human HTori-3 cells and canine thyroid gland. NIS also showed basolateral membrane immunolabeling in follicular cells. All 4 proteins were highly expressed in organoids derived from FTC. The expression was similar or higher compared to the primary tumors. The results of this study characterize organoids derived from canine FTC as a suitable in vitro model to investigate iodine uptake, opening new research possibilities in the field of canine thyroid cancer therapy.

scholarly journals Correlation between the Loss of Thyroglobulin Iodination and the Expression of Thyroid-Specific Proteins Involved in Iodine Metabolism in Thyroid Carcinomas

2003 ◽  
Vol 88 (10) ◽  
pp. 4977-4983 ◽  
Author(s):  
A.-C. Gérard ◽  
C. Daumerie ◽  
C. Mestdagh ◽  
S. Gohy ◽  
C. de Burbure ◽  
...  
Keyword(s):  
Polyclonal Antibodies ◽  
Apical Plasma Membrane ◽  
Hormone Synthesis ◽  
Iodide Transport ◽  
Tissue Sections ◽  
Weak Staining ◽  
Iodine Metabolism ◽  
Specific Proteins ◽  
Generating System

Abstract Progress in biotechnology has provided useful tools for tracing proteins involved in thyroid hormone synthesis in vivo. Mono- or polyclonal antibodies are now available to detect on histological sections the Na+/I− symporter (NIS) at the basolateral pole of the cell, the putative iodide channel (pendrin) at the apical plasma membrane, thyroperoxidase (TPO), and members of the NADPH-oxidase family, thyroid oxidase 1 and 2 (ThOXs), part of the H2O2-generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T4-containing Tg, NIS, pendrin, TPO, ThOXs, and TSH receptor (TSHr) were detected by immunohistochemistry on tissue sections of normal thyroids and various benign and malignant thyroid disorders. Tg was present in all cases. T4-containing Tg was found in the adenomas, except in Hurthle cell adenomas. It was never detected in carcinomas. NIS was reduced in all types of carcinomas, whereas it was detected in noncancerous tissues. Pendrin was not expressed in carcinomas, except in follicular carcinomas, where weak staining persisted. TPO expression was present in insular, follicular carcinomas and in follicular variants of papillary carcinomas, but in a reduced percentage of cells. It was below the level of detection in papillary carcinomas. The H2O2-generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas. Its staining was apical in normal thyroids, whereas it was cytoplasmic in carcinomas. The TSHr was expressed in all cases, but the intensity of the staining was decreased in insular carcinomas. In conclusion, our work shows that all types of carcinomas lose the capacity to synthesize T4-rich, iodinated Tg. In follicular carcinomas, this might be due to a defect in iodide transport at the basolateral pole of the cell. In papillary carcinomas, this defect seems to be coupled to an altered apical transport of iodide and probably TPO activity. The TSHr persists in virtually all cases.

Improved method of thyroid peroxidase extraction from the human thyroid gland

1985 ◽  
Vol 151 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Masahiro Sugawara ◽  
Cassandra L. Thayer ◽  
Takeshi Kita ◽  
Kanji Kuma
Keyword(s):  
Thyroid Gland ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Improved Method

IODINATED THYROLIPIDS: THEIR POSSIBLE ROLE IN HORMONOGENESIS

1973 ◽  
Vol 74 (3) ◽  
pp. 461-474 ◽  
Author(s):  
D. H. Shah ◽  
U. R. Thakare ◽  
R. C. Shownkeen ◽  
D. N. Pahuja ◽  
M. Y. Mandlik
Keyword(s):  
Thyroid Gland ◽  
Lipid Fraction ◽  
Human Thyroid ◽  
Cystic Degeneration ◽  
Nodular Goitre ◽  
Thyroid Glands ◽  
Rat Thyroid ◽  
Rat Thyroid Gland

ABSTRACT A total of 42 human thyroid glands (nodular goitre 9, adenoma with cystic degeneration 6; toxic goitre 10; carcinoma 14; and normal thyroid gland 3) were examined in vitro for iodination of an unidentified polar non-phosphatide lipid fraction (fraction II). The radioiodine incorporation in fraction II was 49.3 %, 43.6 %, 32.8 %, 20.7 %, and 22.0 % respectively in normal, nodular goitre, adenoma with cystic degeneration, toxic goitre and thyroid carcinoma. In vitro studies with surviving sheep thyroid slices did not show any relation between the iodination of fraction II and thyroxine formation over a period of 120 min. However, a highly significant correlation (r-value= 0.96375) was observed between the iodination of fraction II and thyroxine formation in vivo in the rat thyroid gland over a period of 24 h. We have previously postulated that iodination of fraction II may be interrelated to thyroxine formation. In the light of this hypothesis and the above results we suggest that the iodination of fraction II and thyroxine formation in the thyroid gland may be interrelated, the degree of iodination of fraction II being modulated by the amount of thyroxine formed within the thyroid gland.

scholarly journals Human self-reactive T cell clones expressing identical T cell receptor beta chains differ in their ability to recognize a cryptic self-epitope.

1996 ◽  
Vol 183 (2) ◽  
pp. 349-358 ◽  
Author(s):  
S Quaratino ◽  
M Feldmann ◽  
C M Dayan ◽  
O Acuto ◽  
M Londei
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Autoimmune Reaction ◽  
T Cell Clones ◽  
Cell Clones ◽  
T Cell Clone

Recognition of self-antigens by T lymphocytes is a central event in autoimmunity. Understanding of the molecular interactions between T cell receptors (TCR) and self-epitopes may explain how T cells escape thymic education and initiate an autoimmune reaction. We have studied five human in vivo activated T cell clones specific for the region 535-551 of human thyroid peroxidase (TPO) established from a Graves' patient. Three clones (37, 72, and 73) expressed identical TCR beta and alpha chains rearranging V beta 1.1 and V alpha 15.1, and were considered sister clones. Clone 43 differed from clone 37 and its sisters in the J alpha region only. Clone NP-7 expressed V beta 6.5 but rearranged two in-frame TCR alpha chain, both using the V alpha 22.1 segment. Fine epitope mapping using nested peptides showed that clones using identical TCR beta chains, identical V alpha, but a different J alpha recognized distinct, nonoverlapping epitopes in the TPO 535-551 region. This finding shows that a different J alpha region alone leads to a heterogeneous pattern of recognition. This indicates that the "restricted" TCR V region usage sometimes found in autoimmune diseases may not always correspond to identical epitope recognition. To confirm that clones 37 (and its sisters) and 43 recognize different epitopes, the T cell clones were stimulated with a TPO-transfected autologous Epstein-Barr virus (EBV) cell line (TPO-EBV) that presents TPO epitopes afer endogenous processing. Only clone 37 and its sisters recognizes the TPO-EBV cell line, suggesting that the epitope recognized by clone 43 is not presented upon endogenous processing. We have shown that thyroid epithelial cells (TEC), the only cells that produce TPO, express HLA class II molecules in Graves' disease and can act as an antigen-presenting cells, presenting TPO after endogenous processing to autoantigen-reactive T cell clones. We tested, therefore, whether autologous TEC induced the same pattern of stimulation as TPO-EBV; T cell clone 37 recognizes the TEC, whereas it is stimulated poorly by the TPO loaded to autologous peripheral blood mononuclear cells (PBMC). Clone 43, which fails to recognize the TPO-EBV, also fails to recognize the TEC, but is activated by exogenous TPO presented by autologous PBMC. These results show that exogenous versus endogenous processing in vivo generates a different TPO epitope repertoire, producing a "cryptic" epitope (epitope not always available for recognition). Our findings define a route by which human self-reactive T cells may escape thymic selection and become activated in vivo, thus possibly leading to autoimmunity.

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