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Biomedical subjects

N Bagchi

Publications and source records attributed to N Bagchi.

At least 19 recordsLinked to original sources
PubMed1992

What makes silica toxic?

Published data suggest that particle charge could be related to its toxicity. Respirable particles containing silica were therefore collected in foundries and their charge measured. These particles carried high levels of positive charge that were related to low humidity. Incubating these particles with pulmonary macrophages from mice produced detectable activities of collagenase, a precursor of silicosis. These experiments confirm that the toxicity of silica particles is likely to be because of the positive charge they carry.

Animals↗
PubMed1992

The role of iodine in thyroid autoimmunity: from chickens to humans: a review.

Evidence has been presented to support the idea that iodine plays an important role in autoimmune thyroiditis. Excessive amounts induce thyroiditis in genetically susceptible animal strains, while intrathyroidal depletion of iodine prevents disease in strains susceptible to severe thyroiditis. While the mechanisms by which iodine promotes thyroiditis is unknown, several hypotheses have been proposed. (1) T and/or B cells may react specifically to iodinated portions of thyroglobulin (Tg) so that severe iodine depletion renders Tg non-immunogenic. (2) A defect in the iodine processing machinery in thyroid epithelial cells of a susceptible person or animal may, in the presence of iodine, result in elevated levels of oxygen or iodine radicals, which could damage membrane lipids or proteins. (3) Defective iodine processing may result in the iodination of lipid or proteins (other than Tg) which could act either as immunogens or polyclonal activators.

Animals↗
PubMed1991

Uptake and metabolism of iodine is crucial for the development of thyroiditis in obese strain chickens.

To assess the importance of the role of thyroidal iodine in the pathogenesis of thyroiditis in the obese strain (OS) chicken, a model of spontaneous and severe disease, we studied the effect of antithyroid drugs that reduce thyroidal iodine or prevent its metabolism. Reduction of thyroidal iodine was achieved with KClO4, an inhibitor of iodine transport and mononitrotyrosine (MNT), a drug that promotes loss of thyroidal iodine as iodotyrosines. A regimen consisting of KClO4 and MNT administration beginning in ovo and continuing after hatching reduced thyroidal infiltration to 2% of control values and decreased thyroglobulin antibody (TgAb) production for as long as 9 wk. Untreated birds had severe disease by 5 wk of age. The suppression of disease was independent of TSH, not mediated by generalized immunosuppression and reversed by excess dietary iodine. Two drugs that inhibit the metabolism of iodine, propylthiouracil (PTU) and aminotriazole, reduced thyroidal infiltration and TgAb levels, although to a lesser extent. When splenocytes from OS chickens with thyroiditis were transferred to Cornell strain (CS) chickens, a related strain that develops late onset mild disease, only the recipients that were iodine supplemented developed thyroiditis. In conclusion, autoimmune thyroiditis in an animal model can be prevented by reducing thyroidal iodine or its metabolism and optimal effects require intervention at the embryonic stage.

Amitrole↗
PubMed1991

Thyroidal iodine metabolism in obese-strain chickens before immune-mediated damage.

Several studies have shown that iodine plays a role in spontaneous autoimmune thyroiditis in man and other animals. In addition, abnormalities of iodine metabolism have been found in patients with Hashimoto's thyroiditis and in chickens of the obese strain (OS), an animal model of spontaneous autoimmune thyroiditis. We have examined several parameters of iodine metabolism before immune damage in this model and in the related Cornell strain (CS), a strain which develops a late-onset mild thyroiditis, to discover a possible causal relationship between altered iodine metabolism and the initiation of autoimmunity. Thyroglobulin was purified from individual chicken thyroid glands and analysed for iodine by the ceric sulphate method. Analogous to the thyroglobulin of Hashimoto's patients, the iodine content of OS thyroglobulin (27 atoms/molecule) was lower than that of normal-strain thyroglobulin (46 atoms/molecule) when the chickens were provided with a normal diet. Also, under conditions of TSH suppression, the iodine content of OS thyroglobulin (18 atoms/molecule) was lower than that of CS thyroglobulin (36 atoms/molecule) and of normal-strain thyroglobulin (32 atoms/molecule). In contrast with Hashimoto's patients, however, the OS and CS chickens had practically no inorganic iodide in their thyroid glands; electrophoretic analysis of thyroid homogenates revealed that essentially all (greater than 99.62%) 125I was organified by 16 h in all strains of birds tested. Despite the relatively poor iodination of thyroglobulin exhibited by OS chickens, they did not iodinate additional 'unique' proteins, when examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of thyroid proteins labelled with 125I in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Amiodarone-induced changes in lipid metabolism.

Hypothyroidism is a major cause of secondary hypercholesterolemia. Amiodarone treatment alters both the levels of serum lipids and thyroid hormones. We investigated whether the amiodarone-induced changes in lipid metabolism are related to the changes in thyroid hormone levels. Eighteen patients received amiodarone (31 +/- 3 g cumulative dose) for six weeks. Serum triglyceride, total-cholesterol, high density lipoprotein-cholesterol and its subfractions, apolipoproteins B and AI, and plasma post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. Amiodarone treatment caused significant increases in serum total-cholesterol (baseline 4.4 +/- 0.21 (SE), 6 weeks 5.12 +/- 0.26 mmol/l, P less than 0.01), in low density lipoprotein cholesterol (baseline 2.61 +/- 0.26, 6 weeks 3.36 +/- 0.21 mmol/l, P less than 0.05) and in apolipoprotein B (baseline 1.95 +/- 0.15, 6 weeks 2.26 +/- 0.13 mmol/l, P less than 0.01) concentrations. Serum high density lipoprotein and its subfractions, or apolipoprotein AI levels did not change. Plasma post-heparin lipoprotein lipase activity increased (baseline 137 +/- 21, 6 weeks 168 +/- 21 U/ml, P less than 0.01) while hepatic triglyceride lipase did not change. Amiodarone also caused an increase in serum thyroxine (baseline 110 +/- 8, 6 weeks 136 +/- 6 mmol/l, P less than 0.05), although values remained in euthyroid range. In summary, amiodarone therapy increased the concentrations of atherogenic lipoproteins in the serum similar to that seen in hypothyroidism. On the other hand the effect of amiodarone on lipoprotein lipase was opposite to that seen in hypothyroidism. Therefore, amiodarone-induced changes in lipid metabolism cannot be explained solely on the basis of the changes in circulating thyroid hormone levels.

Aged↗
PubMed1990

Antioxidants delay the onset of thyroiditis in obese strain chickens.

Dietary iodine has been shown to be important in the induction of thyroiditis in susceptible chicken strains although the underlying mechanism remains unknown. Iodine may exert its effects through the formation of reactive oxidative radicals which would cause thyroidal injury and initiate infiltration. We have tested this hypothesis by examining the ability of butylated hydroxyanisole (BHA), ethoxyquin, and other antioxidants to prevent thyroiditis in Obese strain (OS) chickens, a strain that develops severe disease by 4 weeks of age. BHA, when administered from hatching until death at 5 weeks of age, reduced thyroidal infiltration and serum levels of antibodies binding thyroglobulin, T3, T4. Similar effects were observed with the antioxidant ethoxyquin. Weaker antioxidants such as vitamins C and E and beta-carotene had only slight or negligible effects on these parameters. BHA reduced thyroiditis in OS chicks killed at 3 and 5 weeks of age, but not at 8 weeks. When BHA treatment was initiated after the development of severe disease, it did not reduce thyroglobulin antibody levels. To determine the mechanism by which BHA reduces thyroiditis, studies were performed to assess the effect of BHA on thyroid function and on the immune responses to exogenous antigens. BHA had no effect on thyroid function in normal strain chickens since thyroidal radioiodine uptake and organification and serum T3 and T4 levels were unaffected. BHA did not alter immune responses to exogenous antigens such as sheep red blood cells or Brucella abortus in OS chickens. In summary, potent antioxidant drugs delayed the onset of thyroiditis when treatment was initiated before the onset of disease, suggesting that reactive oxygen intermediates are involved in the early stages of pathogenesis. However, the site of action remains unknown since they had no detectable effects on thyroid function or general immune responses.

Animals↗
PubMed1990

Thyroid dysfunction in adults over age 55 years. A study in an urban US community.

The prevalence of thyroid dysfunction was determined in a healthy urban population over the age of 55 years. A highly sensitive serum thyrotropin assay was used initially to screen 968 subjects. Elevated values (greater than 6 mU/L) were found in 7.3%, while suppressed values (less than 0.1 mU/L) were present in 2.5% subjects. Protirelin stimulation testing demonstrated exaggerated responses in 95% of the subjects with elevated thyrotropin levels and subnormal responses in 81% of the subjects with suppressed thyrotropin levels. Thyroid dysfunction, as defined by abnormalities of both serum thyrotropin level and protirelin response, was calculated to be present in 8.9% of the population. The prevalence was greater in whites (vs blacks), in women, and in subjects older than 75 years as compared with the 55- to 64-year age group. Hypothyroidism was calculated to be present in 6.9% subjects. Despite an increased prevalence of thyroid autoantibodies in these subjects, only 8.5% of them had subnormal serum thyroxine concentrations. Hyperthyroidism was calculated to be present in 2.0% of the population, two thirds of whom were taking thyroid hormone preparations. These results suggest a significant prevalence of thyroid dysfunction in the elderly, with important sex and racial differences.

Aged↗
PubMed1989

Comparison of the effects of amiodarone and ipodate on the rat heart.

Chronic treatment of rats with amiodarone has been shown to produce hypothyroid-like effects such as a reduction in body and heart weight and increased synthesis of the low ATPase V3-cardiac isomyosin (Bagchi, Brown, Schneider and Banerjee 1987). In this report, we have tested the hypothesis that amiodarone causes these effects through the inhibition of intracellular production of triiodothyronine (T3) from thyroxine (T4) by comparing the effects of amiodarone with those of ipodate, a potent inhibitor of T4 to T3 conversion. Separate groups of rats were given dietary ipodate and amiodarone respectively for six weeks. Both agents increased serum T4 and T4/T3 ratios, a finding consistent with the inhibition of peripheral T4 to T3 conversion. However, ipodate failed to produce hypothyroid-like effects on body weight, heart weight and isomyosin transitions similar to those found in the amiodarone group. These data indicate that the hypothyroid-like effects of amiodarone on the rat heart are not due to the inhibition of intracellular generation of T3 from T4.

Amiodarone↗
PubMed1989

Loss of pubic and axillary hair following treatment with glucocorticoids.

A woman with prior bilateral oophorectomy developed loss of pubic and axillary hair following treatment with glucocorticoids. Serum androgens were low while cortisol and aldosterone levels were normal. This unusual presentation, which continued for at least 3 years, was most likely attributable to the prolonged selective suppression of adrenal androgens by glucocorticoids.

Aldosterone↗
PubMed1988

Decreased thyroidal response to thyrotropin in type II diabetes mellitus.

The responses to TRH and bovine TSH (bTSH) were compared in 19 men with uncontrolled type II diabetes mellitus and eight healthy control subjects. Baseline serum TSH, T3 and T4 were similar in both groups and the rise of serum TSH, T3 and T4 following the intravenous (IV) administration of TRH (500 micrograms) was not significantly different. Diabetic subjects showed a blunted response to the subcutaneous (sc) administration of bTSH (5 U) when their maximal serum T3 and T4 values were compared with controls (T4, 9.4 +/- 0.3 v 12.3 +/- 1.1 micrograms/dL, P less than .005; T3, 185 +/- 9 v 233 +/- 17 ng/dL, P less than .025; diabetic v control). When the response to bTSH was examined in seven patients after 4 to 5 days of strict glycemic control, the maximal T3 response was found to increase in six, and the maximal T4 response in five. These data show that the thyroidal secretory response to large doses of TSH is decreased in uncontrolled diabetes mellitus and that strict glycemic control frequently improves the response.

Adult↗
PubMed1987

Effect of amiodarone on rat heart myosin isoenzymes.

The effects of amiodarone on heart weight, production of 14C-CO2 from labelled glucose, myosin ATPase activity, and myosin isoenzyme patterns were determined by comparing control and amiodarone-treated male Wistar rats. Since it has been suggested that amiodarone may interfere with thyroid hormone action on the heart, similar experiments were also carried out in hypothyroid and amiodarone-plus-triiodothyronine(T3)-treated rats, and the data were compared to those obtained in amiodarone-treated rats. Amiodarone treatment for 6 weeks resulted in lower heart weight, decreased atrial production of 14C-CO2 from labelled glucose, decreased myosin Ca-ATPase activity, and preferential synthesis of V3 isomyosin. These effects were similar to those observed in hypothyroid rats but were lesser in magnitude. T3 treatment of amiodarone-treated rats reversed all the changes induced by amiodarone. Serum thyroxine (T4) was higher in amiodarone-treated than in control rats, while serum T3 was similar. Serum T3 was higher in the amiodarone-plus-T3 than in the amiodarone-treated group. These results show that 1) amiodarone-induced changes resemble hypothyroidism with respect to cardiac myosin expression and atrial CO2 production, 2) amiodarone causes hypothyroid-like changes despite normal serum T3 and increased serum T4, and 3) T3 reverses the effects of amiodarone. These data support the hypothesis that amiodarone inhibits the action of thyroid hormone on the heart.

Adenosine Triphosphatases↗
PubMed1985

Studies on the mechanism of acute inhibition of thyroglobulin hydrolysis by iodine.

Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of NaI to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4Cl and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Chloride↗
PubMed1985

Repeated thyrotrophin stimulation of thyroid secretion: lack of refractoriness in vivo.

It has been reported that prior exposure of thyroid tissue to TSH in vitro induces a state of refractoriness to new challenges of the hormone. We have investigated the effect of repeated TSH treatment on thyroid secretion to determine whether such refractoriness exists in vivo. The rate of thyroid secretion was estimated by measuring the rate of hydrolysis of labelled thyroglobulin from mouse thyroid glands in vitro. The thyroid glands were labelled in vivo with 131I and then cultured for 20 h in the presence of mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the percentage of radioactivity released as free iodotyrosines and iodothyronines into the gland and the medium at the end of incubation. Thyrotrophin was administered in vivo at hourly intervals for 2-4 injections. The corresponding control group received saline injections every hour except for the last injection when they received TSH. The peak rates of thyroglobulin hydrolysis, measured 2 h following the last injection, were similar in animals receiving two, three or four TSH injections and were not different from those in the control groups. Serum triiodothyronine and thyroxine concentrations 2 h after the last injection were higher in the groups receiving multiple TSH injections. Thyroidal cyclic AMP accumulation in response to TSH was markedly depressed in the group receiving multiple injections compared with the group receiving a single injection of TSH in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1977

Effect of inorganic iodide on thyroglobulin hydrolysis in cultured thyroid glands.

The process of thyroglobulin hydrolysis in mouse thyroid glands labelled in vitro was studied from 2-24 h after they had been maintained in tissue culture. The culture medium was supplemented with mononitrotyrosine to prevent deiodination of iodotyrosines. Hydrolysis of labelled thyroglobulin, under these conditions, led to the release of labelled iodotyrosines and iodothyronines. The rate of formation of these compounds was measured as an index of thyroglobulin hydrolysis (TH). TH was markedly stimulated by TSH. NaI inhibited TSH stimulation of TH at a concentration of 10(-5)M or greater. NaI, at similar concentrations,also markedly diminished or abolished the incorporation of 131I into thyroidal proteins from radioiodide-supplemented media. The addition of various inhibitors of iodination effectively blocked the effect of iodide on TH. In experiments where radioimmunossay was used to measure medium hormone concentrations, the release of unlabelled thyroxine (T4) and triiodothyronine (T3) induced by TSH was found to be significantly decreased in the presence of 10(-4)M NaI. These studies demonstrate that iodide inhibits the hydrolysis of thyroglobulin at or near concentrations which also inhibit iodination of thyroidal proteins. The present data suggest that formation of an iodinated compound is necessary for the effect of iodide. In addition, these studies demonstrate the utility of this in vitro system for the investigation of thyroid physiology.

Hydrolysis↗