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At least 37 records · Page 2Linked to original sources

Peripheral cytokine expression in autoimmune thyroiditis: effects of in vitro modulation by rosiglitazone and dexamethasone.

BACKGROUND: In Hashimoto's thyroiditis (HT), there is evidence for activation of peripheral T-lymphocytes that predominantly express a T helper 1 (T(H)1) cytokine bias. However, the immunomodulatory factors involved in regulating this response have so far received scant attention. In this study, we examine the effects of the glucocorticoid, dexamethasone, and the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand, rosiglitazone on the expression of interferon (IFN)-gamma (T(H)1) and interleukin (IL)-4 (T(H)2) by activated peripheral CD4(+) and CD8(+) lymphocytes in patients with HT (n = 10) and healthy control subjects (n = 12). METHODS: Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with phorbolmyristate acetate (PMA) and ionomycin in the presence or absence of varying doses of dexamethasone and rosiglitazone (0.01 microM, 1.0 microM, and 100 microM). Cytokine expression was determined by flow cytometry. RESULTS: CD4(+) and CD8(+) IFN-gamma expression was greater in HT than controls (14.87 versus 9.25; p < 0.05 and 21.34 versus 10.16; p < 0.01, respectively). A dose-dependent inhibition of IFN-gamma expression was seen with dexamethasone and rosiglitazone. Inhibition of CD4(+) and CD8(+) IFN-gamma expression with both dexamethasone and rosiglitazone was greater in control subjects than in patients (p < 0.05). There was no significant difference in IL-4 expression between patients and control groups and its expression remained unaffected by either compound. CONCLUSIONS: We show that CD4(+) and CD8(+) T lymphocytes from HT patients express a type 1 cytokine bias that is significantly more resistant to in vitro modulation by rosiglitazone and dexamethasone. Further studies are needed to clarify if this resistance plays a role in the pathogenesis of autoimmune thyroid disease (AITD).

Adult↗

Lithium: thyroid effects and altered renal handling.

BACKGROUND: Lithium is frequently used in the treatment of bipolar affective disorder, and is widely known to affect thyroid function, most commonly resulting in hypothyroidism and goiter. Less well-known is the association between lithium therapy and hyperthyroidism and the potential for lithium to moderate the effects of thyroxine at a cellular level. Lithium excretion relates principally to glomerular filtration rate and proximal tubule function. Thyroxine, through its effects on tubular function, alters lithium clearance such that thyroid disease may cause retention of lithium and subsequent toxicity. CASE REPORTS: We report 2 cases with lithium toxicity, both of whom were later found to be hyperthyroid. One patient developed thyroid storm following dialysis to remove lithium. The other received antithyroid medication early. Both suffered a protracted multifactorial delirium requiring intensive inpatient care. CONCLUSION: In addition to altering thyroid function, lithium therapy may mask the signs of hyperthyroidism by inducing cellular unresponsiveness. In some lithium-treated patients with biochemical hyperthyroidism, early antithyroid treatment may be appropriate. Altered renal tubular function induced by hyperthyroidism may result in retention of lithium and systemic toxicity. We propose induction of the proximal tubule sodium hydrogen antiporter as the relevant mechanism.

Adult↗

[Crystalline inclusions of the mouse thyroid. Effect of chronic treatment with lithium gluconate].

Intracytoplasmic crystalline bodies of various sizes are found in thyroid cells of 10-month-old mice and in younger animals under chronic lithium treatment. They are frequently surrounded by small microvesicles and dense bodies or enclosed in larger vesicles having a dense content. The crystalline skeleton is a network of protein fibers assembled in a characteristic axis with a periodicity of 8 nm. A deficiency of thyroid cell metabolism related to aging or lithium gluconate treatment would lead to an accumulation of substances of a crystalline pattern.

Aging↗

Avian thyroid: effect of p,p'-DDT on size and activity.

Feeding sublethal amounts of p,p'-DDT to pigeons caused an increase in thyroid weight and a reduction in colloid content of the follicles. This may reflect a hyper- or hypo-functioning gland and may be cotnnected with recent reductions in egg shell weights in wild birds. The effect was accompanied by increased liver weight.

Animal Feed↗

Reproductive and thyroid effects of low-level polychlorinated biphenyl (Aroclor 1254) exposure.

As little information is available on the adverse effects of polychlorinated biphenyls (PCBs) on the reproductive system of the male rat, the current study was conducted to evaluate the effects of subchronic administration of the PCB mixture Aroclor 1254 on testicular gamete production and endocrine function. The thyroid hormone thyroxine (T4), which is critical for reproduction and development, was also measured because of the well-documented effects of PCBs on this hormone. Weanling (31-day-old) male Fischer rats were administered 0, 0.1, 1, 10, or 25 mg/kg/day Aroclor 1254 by gavage for 5, 10, or 15 weeks and necropsied. The hormones testosterone (T) and thyroxine were measured in the serum, and body weight and weights of the liver, kidney, testes, seminal vesicle plus coagulating gland, cauda epididymides, and pituitary were taken. At 10 and 15 weeks, testicular interstitial fluid (IF) was collected and T concentration in the IF was measured. Sperm motility was measured from a caudal sperm sample and sperm numbers in the testis and cauda epididymis were determined. In addition, tissues were examined microscopically for histopathological alterations. In the high-dose group, body, seminal vesicle, cauda epididymal, and pituitary weights were depressed at 10 and 15 weeks and cauda epididymal sperm numbers were reduced after 15 weeks of dosing. In contrast, testes weights, testicular sperm numbers, sperm motility, and serum and testicular testosterone levels were unaffected, even in the highest dose group (25 mg/kg/day). Aroclor 1254 administration produced histological alterations in the liver and kidney at doses of 1.0 mg/kg/day and above.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pituitary-thyroid interaction: effects of thyroid hormone, non thyroidal illness and various agents on TSH secretion.

Recent developments in thyroid hormone metabolism have helped to understand the complex events which characterize the regulation of TSH secretion. Plasma T3 concentration as well as intrapituitary T3 generation from T4, exert a profound effect on TSH synthesis and release. Pituitary Type II deiodinase differs from Type I deiodinase found in other tissue such as liver and kidney, and in fact different conditions such as hypothyroidism and hyperthyroidism affect these enzymes in opposite direction. Thyroid hormones exert other effects on the pituitary such as increased synthesis of substance P, increased synthesis of GH, and decreased TRH receptors, TRH also modifies its own receptors in the pituitary and exerts modulatory effects on TSH molecule. Patients with non thyroidal illness may display TSH molecules with decreased biological activity. Various agents used in every day praxis may alter TSH and thyroid secretion. The physician must be aware of changes in order to avoid diagnostic pitfalls.

Animals↗

Thyroid effects on adenosine 3',5'-monophosphate levels and adenylate cyclase in cultured neuroblastoma cells.

Using neuroblastoma cells as a model of developing neurons, we have tested the hypothesis that thyroid hormones alter cAMP metabolism. Neuroblastoma cells were grown in serum-free defined medium for 48 h with or without thyroid hormones. Treatment with 20-200 nM 3,5,3'-triiodo-L-thyronine (T3) increased the accumulation of cAMP by intact cells without altering growth, gross morphology, or DNA or protein content. The increase in cAMP accumulation could be detected 5 h after the addition of T3 and was abolished by the addition of cycloheximide. The maximum stimulation produced by prostaglandin E1 was increased in T3 cells without a significant alteration of the half-maximal concentration. T4 and D-T3 in concentrations up to 20 microM did not increase cAMP accumulation. Adenylate cyclase activity in response to forskolin, guanine nucleotides, and stimulatory hormones was increased in purified membranes from cells grown in T3, suggesting that increased adenylate cyclase is probably the major mechanism of the observed response to thyroid hormone.

Adenylyl Cyclases↗

Use of radioiodine urinalysis for effective thyroid blocking in the first few hours post exposure.

A useful correlation between maximum thyroid uptake and radioiodine urine levels at different times after exposure was developed in order to determine when the intervention with an adequate blocking agent might still be effective. In an animal model (dog), six different doses were administered in the range of 100-600 kBq. The best correlation was found between the 125I uptake after 48 h (T-48) and urine radioactivity 4-6 h (U-4, U-5, U-6) after exposure. For the case of U-4, the equation Y(T-48) = 0.790 X(U-4) + 2.973 (r = 0.974 with a level of significance of p < 0.001) was obtained. An analogous study, carried out in humans (n = 20) to whom 1311 was administered, showed a similar correlation and level of significance: Y(T-24) = 1.162 X(U-4)+3.263 (r = 0.926; p < 0.001). The validity of this correlation was confirmed in four volunteers who received small doses of 125I(25-100 kBq), with good agreement between measured and extrapolated thyroid uptake and a mean difference of less than 10% (CV = 16.2%). Three different blocking agents were then tested in the same dog: potassium iodide, potassium perchlorate, and a thionamide (Tapazole). The blocking action of the first two compounds was about 90%, as opposed to only 48% for the third compound. Potassium iodide was chosen for its limited side effects and more universal utilization. The final study, carried out with four different doses, indicated that 25 mg of KI is the ideal amount to be administered to the dog. This corresponds to approximately 100 mg for a 70 kg human being (i.e., 1.4 mg kg(-1)). This dose, when administered to a volunteer 4 h after exposure, provided a thyroid blocking of 68%.

Administration, Oral↗