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Biomedical subjects

N Bagchi

Publications and source records attributed to N Bagchi.

At least 37 records · Page 2Linked to original sources
PubMed1987

Effect of amiodarone on serum lipids, lipoprotein lipase, and hepatic triglyceride lipase.

We have determined the effects of chronic amiodarone treatment on lipid metabolism and compared them with those of hypothyroidism in the rat. Serum triglyceride was lower in both amiodarone-treated and hypothyroid rats; total cholesterol was higher in hypothyroid rats, and serum high density lipoprotein cholesterol remained unchanged. Amiodarone increased adipose tissue lipoprotein lipase activity. Hepatic triglyceride lipase activity was decreased in both hypothyroid and amiodarone-treated groups. The effects of amiodarone on serum triglyceride and adipose tissue lipoprotein lipase were reversed by concomitant administration of T3. The activity of hepatic triglyceride lipase, however, was not increased. Our findings indicate that amiodarone causes marked changes in lipid metabolism which are similar to those found in hypothyroidism.

Adipose Tissue↗
PubMed1987

The incorporation of dietary iodine into thyroglobulin increases its immunogenicity.

Experiments were performed to analyze one mechanism by which elevated levels of dietary iodine may induce thyroglobulin (Tg) autoantibodies. We tested the hypothesis that highly iodinated Tg synthesized by animals fed a high iodine diet is significantly more immunogenic than Tg containing fewer iodine atoms. Cornell strain (CS) chickens, genetically susceptible to iodide-induced thyroiditis, were fed either a high or a low iodine diet. They were killed, and their thyroidal Tg was analyzed for iodine; the high iodine Tg (HI-Tg) had at least 60 and the low iodine Tg (LI-Tg) had less than 13 atoms/molecule of Tg. To determine if the degree of Tg iodination affected its immunogenicity, these Tg preparations were administered iv to normal chickens without adjuvants. Their sera were tested for antibodies by direct binding radioassays and RIAs. HI-Tg stimulated the synthesis of antibodies that reacted well with HI-Tg and the thyroid hormones T3 and T4, but only weakly with LI-Tg. The birds immunized with LI-Tg produced very little antibody to LI-Tg, T3, or T4, but a modest amount to HI-Tg. In other experiments, Tg autoantibodies found in chickens maintained on a high iodine diet similarly demonstrated enhanced binding to HI-Tg. The present studies show that HI-Tg is more immunogenic than LI-Tg and supports the hypothesis that a high iodine diet induces Tg autoantibodies by increasing the immunogenicity of the Tg molecule. In marked contrast with iodide-induced Tg antibodies, the Tg antibodies accompanying the severe and early-onset thyroiditis of obese strain chickens are to a large degree independent of dietary iodine intake.

Animals↗
PubMed1987

Detrimental effect of recent thyroidectomy on hemorrhagic shock and resuscitation.

Shatney and coworkers, in 1984, reported that recent thyroidectomy in dogs improved survival following hemorrhagic shock induced by reservoir bleeding to a mean pressure (MAP) of 60 torr for 60 min. Since thyroidectomy reduces preshock MAP, their control dogs had a relatively greater fall in MAP during hemorrhage. To circumvent this inequity, this study was designed to elucidate the effects of recent thyroidectomy in 20 splenectomized dogs subjected to acute hemorrhagic shock induced by phlebotomy of a predetermined volume of blood independent of resultant MAP. During splenectomy, ten dogs had thyroidectomy with parathyroid preservation and ten dogs had sham neck operation; 12 days later, hemorrhagic shock was induced by the stepwise bleeding of 35 ml/kg body weight over 75 min. Parameters measured at preshock (baseline), postshock (PS), postresuscitation (PR), and day 2 included MAP, cardiac output (CO), wedge pressure (PCWP), T3, T4, TSH, and hematocrit (Hct). Hypothyroidism was confirmed by low T3 and T4. Baseline and PS hemodynamic parameters were similar for both groups; PR data showed a significant rise in CO (6.7 liter/min vs 3.9 liter/min) and a fall in PCWP (13.2 mmHg vs 18.6 mmHg) in the euthyroid dogs compared to the hypothyroid dogs. Increased CO persisted through day 2 in the euthyroid dogs (3.14 liter/min vs. 1.95 liter/min). Four thyroidectomized dogs died during shock compared to one control dog. Contrary to prior data, this study shows that recent thyroidectomy reduces the survival and compensatory response to hemorrhage. The mechanism leading to this impaired response needs to be defined.

Animals↗
PubMed1986

Adaptation of male and female rats to iodine deficiency.

The response of the hypothalamic pituitary axis to chronic iodine deficiency was compared in male and female Sprague-Dawley rats. The animals were kept on a low iodine diet for 12 weeks. Blood samples as well as thyroid and pituitary weights were obtained every two weeks. Baseline values of thyroid weight and serum thyroxine (T4) were similar in both sexes. However, females had lower serum TSH and higher serum triiodothyronine (T3), pituitary weight and pituitary TSH content. After initiation of the low iodine diet, both sexes showed similar decreases in serum T4 and similar increases of serum TSH and thyroid weight. Serum T3, pituitary weight and TSH content remained higher in females throughout the study. Pituitary TSH was directly correlated with serum TSH in both sexes. When adjusted for pituitary TSH and analyzed by a stepwise regression analysis, serum TSH was lower in females suggesting a difference in TSH secretion between males and females. Our studies demonstrate significant sex differences in the regulation of TSH secretion and maintenance of serum T3 level in response to a chronic stimulus.

Adaptation, Physiological↗
PubMed1985

Induction of autoimmune thyroiditis in chickens by dietary iodine.

Clinical studies have suggested that excess dietary iodine promotes autoimmune thyroiditis; however, the lack of a suitable animal model has hampered investigation of the phenomenon. In this study, different amounts of potassium iodide were added to the diets of chicken strains known to be genetically susceptible to autoimmune thyroiditis. Administration of iodine during the first 10 weeks of life increased the incidence of the disease, as determined by histology and the measurement of autoantibodies to triiodothyronine, thyroxine, and thyroglobulin. Further support for the relation between iodine and autoimmune thyroiditis was provided by an experiment in which iodine-deficient regimens decreased the incidence of thyroid autoantibodies in a highly susceptible strain. These results suggest that excessive consumption of iodine in the United States may be responsible for the increased incidence of autoimmune thyroiditis.

Animals↗
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↗
PubMed1985

Analysis of triiodothyronine and thyroxine-binding autoantibodies in chickens susceptible to autoimmune thyroiditis.

This report reveals a surprisingly high incidence of thyroid hormone (T3 and T4) autoantibodies (THA) and thyroglobulin autoantibodies in a closed flock of untreated Cornell strain (CS) White Leghorn chickens. This flock is closely related to the Obese strain chicken, which develops a severe spontaneous autoimmune thyroiditis. A sensitive electrophoretic autoradiographic assay for THA was developed. This assay was applied to the study of autoantibodies to T3 and T4 in the sera of adult female CS chickens. Of 109 females, 29.4% had antibodies to T3 and 18.4% had antibodies to T4. The incidence of thyroglobulin antibodies, determined by passive hemagglutination, was 15.6%. The presence of THA affected RIA measurements because serum T3 and T4 hormone concentrations appeared elevated in those birds with moderate to high antibody levels. There was major variance in the electrophoretic heterogeneity of the THA from individual chickens; i.e., some of the sera contained antibodies to T3 or T4 that appeared to be monoclonal, whereas other sera exhibited polyclonal multi-banded patterns. To determine if antibodies reactive with T3 and T4 (which are haptens) were generated by antibody responses to the T3/T4 sites on the thyroglobulin molecule, competitive binding assays were performed to determine the relative binding affinities of the antibodies for the haptens (T3/T4) and the "hapten-conjugate" (thyroglobulin). In these assays, thyroglobulin competed with the haptens, thus supporting the above hypothesis.

Animals↗
PubMed1984

Effects of castration and sex steroids on the thyroid response to thyrotropin.

There is a profound difference in the incidence of thyroid disease between males and females. We have investigated the possibility of a direct effect of sex steroids on the thyroid gland by investigating thyroid function in castrate animals. The rate of thyroid hormone release was estimated by measuring the rate of hydrolysis of labeled thyroglobulin from mouse thyroid glands in vitro. The thyroid glands were labeled in vivo with 131I and then cultured for 20 h in the presence of mononitrotyrosine, an inhibitor of iodotyrosine and deiodinase. The rate of hydrolysis of labeled thyroglobulin was measured as the percentage of radioactivity released as iodotyrosines and iodothyronines into the gland and the medium at the end of incubation. TSH was injected at varying intervals before death in some cases. The basal rates of thyroglobulin hydrolysis were similar in intact and castrate mice, but TSH-stimulated rates were significantly higher in both male and female castrates. Daily treatment of castrates for a week with estradiol or testosterone decreased the rate of thyroglobulin hydrolysis to that seen in intact mice, but dihydrotestosterone was without effect. (Bu)2cAMP added in vitro increased the rate of thyroglobulin hydrolysis in both intact and castrate mice, but the stimulation was significantly greater in the castrates. Basal and TSH-stimulated cAMP levels in the thyroid were similar in castrate and intact mice. There was no difference in thyroidal incorporation of iodine by intact and castrate mice in either presence or absence of TSH. These data suggest the following. 1) Castration results in significantly greater sensitivity to TSH with respect to thyroid hormone secretion. Thyroid hormone synthesis, basal or TSH-stimulated, is, however, unaltered. 2) Estradiol inhibits TSH-stimulated hormone release in castrates. Testosterone has a similar effect, possibly through aromatization to estradiol. 3) The effect of sex hormones is likely to be exerted at a post-cAMP step specific for hormone secretion.

Animals↗
PubMed1982

Effect of chronic lithium treatment on hypothalamic-pituitary regulation of thyroid function.

We have previously observed that chronic treatment with Li causes a decrease in the goitrogenic response to iodine deficiency in rats. Since this is likely to be mediated by an alteration of thyrotropin (TSH) secretion, we have investigated the hypothalamic and pituitary function of rats fed an iodine deficient Li supplemented diet for 16 weeks. The Li group had lower thyroid and pituitary weights than the corresponding control group. Plasma thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were low and comparable in both groups but plasma TSH was significantly lower in the Li group. There was no difference in the TSH content of pituitaries in the two groups. TSH release from the pituitaries in vitro was similar in both groups in the basal state as well as upon stimulation by thyrotropin releasing hormone (TRH). We conclude that chronic treatment with Li blunts the TSH response to iodine deficiency. The data also provide indirect evidence that the effect of Li is exerted at the hypothalamic rather than at the pituitary level.

Animals↗
PubMed1982

Thyroid function in a diabetic population.

Several alterations in thyroid function are found in diabetes mellitus (see Table I). The most profound changes occur in patients with insulin-dependent diabetes. Plasma T4 is normal whereas plasma T3 is diminished, and the plasma level of rT3 is elevated in diabetic ketoacidosis or in patients with severely uncontrolled diabetes. These changes arise from alterations in the monodeiodination pathways of T4. Both hypo- and hyperthyroidism occur with increased frequency in diabetes. There is an increased prevalence of thyroid autoantibodies in insulin-dependent diabetics. Animals studies suggest a defect in the hypothalamic regulation of the thyroid-pituitary feedback system and an impaired response of the thyroid gland to TSH. Clinical studies are not yet available to confirm the occurrence of these regulatory disturbances in human diabetic patients. It is not clear whether the deiodination and regulatory changes in thyroid hormone economy that are associated with diabetes result in hypothyroidism at the cellular level.

Animals↗
PubMed1981

Decreased thyroidal response to thyrotropin in diabetic mice.

The effect of diabetes mellitus on the synthesis and secretion of thyroid hormone ws investigated in mice with streptozotocin-induced diabetes. Thyroid glands were labeled in vivo with 131I for 2 h. In control animals, TSH stimulated the synthesis of PB127I and 131I-labeled iodothyronines and simultaneously decreased the proportion of 131I-. These effects of TSH were not observed in diabetic animals but were demonstrable in diabetic animals treated with insulin. For studies of hormone secretion, labeled thyroid glands were cultured in vitro in medium containing 1 mM mononitrotyrosine. The rate of the hydrolysis of labeled thyroglobulin was measured as the proportion of 131I-labeled iodotyrosines and 131I-labeled iodothyronines recovered at the end of culture and was used as an index of thyroid secretion. TSH in vivo stimulated the rate of thyroglobulin hydrolysis for 6 h, with a peak occurring after 2 h. The diabetic mice had a diminished response to TSH, which improved on treatment with insulin. The addition of TSH and insulin to the culture medium significantly increased the rate of thyroglobulin hydrolysis in glands of diabetic mice over that resulting from the addition of dibutyryl cAMP alone. The generation of thyroidal cAMP in response to TSH was higher in diabetic mice than in controls. The rise in plasma T4 and T3 2 h after the administration of TSH was less in diabetic mice than in control mice or diabetic mice treated with insulin. Our studies, therefore, indicate that the thyroidal response to TSH is decreased in diabetes mellitus. The defect appears to be at a step beyond the generation of cAMP.

Animals↗
PubMed1980

Role of the heterogeneity of thyroglobulin in the secretion of thyroid hormone in mice.

The rates of thyroglobulin hydrolysis and iodothyroine release from mouse thyroid glands were studied in vitro. Recently iodinated thyroglobulin ('new pool') had been labelled during life by injection of 131I 3 h before removal of the thyroid, 'old pool' thyroglobulin had been labelled by the administration of 125I in the drinking water for 1 week starting 3 weeks earlier. Chromatogrphic analysis of pronase digests of the thyroid glands showed that the iodothyronine content of the old and new pools were 19.5 and 7.4 per cent respectively. In the basal state the rate of thyroglobulin hydrolysis was lower from the old pool but the rate of hormone secretion was similar from both pools. Thyrotrophin (TSH) increased the rate of thyroglobulin hydrolysis and hormone release from both pools by up to four to six times the basal rate, the effect being maximal 2 h after administration of TSH and lasting for 6-8 h. The rate of thyroglobulin hydrolysis after TSH was similar in both pools but the rate of release of labelled iodothyronines was significantly higher from from the old pool. These studies have indicated that although hydrolysis of thyroglobulin paroceeds faster in the new pool than in the old ('last come, first served' hypothesis) neverrtheless there is no difference in the rate of hormone secretion from the two pools, and hydrolysis in both pools is affected by TSH.

Animals↗
PubMed1980

Pre-precipitated and solid-phase second antibody compared in radioimmunoassay.

We describe simple methods for preparing and determining the titer of pre-precipitated second antibody. We compared the performance of this type of insolubilized second antibody with that of a commercially available solid-phase second antibody (DASP) for separation of reverse triiodothyronine (rT3) and for thyrotropin radioimmunoassays. Equilibrium time for both reagents was about 30 min, considerably briefer than for the usual second-antibody procedure. Within-assay precision was improved and percentages of nonspecific binding (mean and SD) were lower if pre-precipitated second antibody was used in both assays [rT3 pre-precipitate = 1.48 (SD 0.16), rT3 DASP = 3.76 (SD 0.22); thyrotropin pre-precipitate = 1.45 (SD 0.18), thyrotropin DASP = 3.45 (SD 0.26)]. The cost of DASP was three to 10 times that of pre-precipitated second antibody prepared with commercially available products.

Antibodies↗
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↗