Actions and interactions of thyroid hormone and zinc status in growing rats.
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Both thyroid hormone (triiodo-L-thyronine, T3) and zinc play important roles in growth and development. The T3 receptor is thought to require zinc to adopt its biologically active conformation. Some of the effects of zinc deficiency, therefore, may be due to loss of zinc from the T3 receptor and impairment of T3 action. This possibility was investigated in growing rats by examining the effects of hypothyroidism and hyperthyroidism in zinc-deficient, pair-fed and control rats. Measurement of serum zinc and T3 confirmed the efficacy of the treatments. Zinc deficiency and hypothyroidism resulted in lower food intake and growth failure, but no interaction was observed between the two treatments. Individual tissue weights were influenced by thyroid status as expected, regardless of zinc status. Both dietary and hormonal treatments influenced serum insulin-like growth factor (IGF)-I in an interactive manner. IGF-I was reduced to a greater extent in zinc-deficient than in pair-fed rats compared with controls. Both hypothyroidism and hyperthyroidism reduced serum IGF-I, and a greater reduction due to hyperthyroidism was apparent in zinc-deficient rats. IGF binding proteins were also influenced by diet and thyroid status. The hepatic expression of mRNA S14 was assessed as a direct index of the nuclear action of T3, but its response was not influenced by dietary treatment. Although confirming the role of both T3 and zinc in the regulation of growth and the somatotrophic axis, the growth failure of zinc deficiency does not appear to be due to impaired T3 function. (+info)
Thyroid status influences baroreflex function and autonomic contributions to arterial pressure and heart rate.
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The effect of thyroid status on arterial baroreflex function and autonomic contributions to resting blood pressure and heart rate (HR) were evaluated in conscious rats. Rats were rendered hyperthyroid (Hyper) or hypothyroid (Hypo) with triiodothyronine and propylthiouracil treatments, respectively. Euthyroid (Eut), Hyper, and Hypo rats were chronically instrumented to measure mean arterial pressure (MAP), HR, and lumbar sympathetic nerve activity (LSNA). Baroreflex function was evaluated with the use of a logistic function that relates LSNA or HR to MAP during infusion of phenylephrine and sodium nitroprusside. Contributions of the autonomic nervous system to resting MAP and HR were assessed by blocking autonomic outflow with trimethaphan. In Hypo rats, the arterial baroreflex curve for both LSNA and HR was shifted downward. Hypo animals exhibited blunted sympathoexcitatory and tachycardic responses to decreases in MAP. Furthermore, the data suggest that in Hypo rats, the sympathetic influence on HR was predominant and the autonomic contribution to resting MAP was greater than in Eut rats. In Hyper rats, arterial baroreflex function generally was similar to that in Eut rats. The autonomic contribution to resting MAP was not different between Hyper and Eut rats, but predominant parasympathetic influence on HR was exhibited in Hyper rats. The results demonstrate baroreflex control of LSNA and HR is attenuated in Hypo but not Hyper rats. Thyroid status alters the balance of sympathetic to parasympathetic tone in the heart, and the Hypo state increases the autonomic contributions to resting blood pressure. (+info)
Effect of low-intensity warfarin therapy on left atrial thrombus resolution in patients with nonvalvular atrial fibrillation: a transesophageal echocardiographic study.
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The presence of left atrial thrombus (LAT) is associated with an increased risk of embolic stroke. However, it has yet to be established definitively whether low-intensity warfarin therapy (INR: 1.5-2.0) can prevent LAT formation in patients with nonvalvular atrial fibrillation (NVAF). The present study analyzed the clinical and transesophageal echocardiography (TEE) features of 123 such patients to identify risk factors for LAT formation and the efficacy of prophylactic low-intensity warfarin therapy. Left atrial thrombi were found in 35 patients (28%) in whom systemic hypertension (49% vs 23%; p<0.01) and ischemic heart disease (17% vs 3%; p<0.01) were more frequent. Left ventricular ejection fraction (54+/-14% vs 60+/-11%; p<0.05), left ventricular end-diastolic dimension (51+/-7 mm vs 48+/-5 mm; p<0.05), spontaneous echo contrast (2.2+/-0.7 vs 1.4+/-0.9; p<0.01), left atrial diameter (50+/-6 mm vs 43+/-7 mm; p<0.01), left atrial appendage blood velocity (22.3+/-8.7 cm/s vs 37.2+/-21.5 cm/s; p<0.01) and the incidence of left ventricular hypertrophy (37% vs 15%; p<0.01) were also significantly different between the groups. Fourteen patients received continuous warfarin therapy (target INR: 1.5-2.0) and on the follow-up TEE study the left atrial thrombus resolved in 10 (71%). There were no thromboembolic events or major hemorrhagic complications in these patients, so it was concluded that low-intensity warfarin therapy is efficacious in treating LAT formation in patients with NVAF. (+info)
Paradoxical hormonal and behavioral responses to hypothyroid and hyperthyroid states in the Wistar-Kyoto rat.
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Wistar-Kyoto (WKY) rats show endogenous depressive behavior that can be reversed by antidepressants. Given that WKYs exhibit decreased sensitivity to some antidepressants and treatment-resistant depressed patients often show hypothalamic-pituitary-thyroid (HPT) dysregulation, we examined the behavioral and HPT hormonal responses of WKYs to altered thyroid status. "Euthyroid" WKYs had elevated basal plasma TSH and T(3) levels as compared to Wistars. Hypothyroidism increased TSH levels more in WKYs than in Wistars and increased response latency in the open field test (OFT) of WKYs only. Administration of T(4) and T(3) suppressed plasma TSH equally in both strains. Wistars responded to increased T(3) levels with decreased response latency and increased activity in the OFT, but increased immobility in the forced swim test. In contrast, WKYs responded only to the high T(3) levels with decreased response latency in the OFT. These results suggest the existence of a decreased central nervous system sensitivity to thyroid hormones in WKYs that could be related to their depressive behavior. (+info)
A multiple ligand-binding radioimmunoassay of diiodotyrosine.
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A radioimmunoassay has been developed for the measurement of 3,5-diiodo-L-tyrosine (DIT) in serum. DIT was coupled to porcine thyroglobulin (PTg) with a molar ratio of 205:1. Rabbits were immunized with 1 mg of immunogen emulsified in complete Freund's adjuvant. Sera were screened for their ability to bind trace amounts of [125I]DIT. A serum that bound 40% of the tracer at a final dilution of 1:1,750 was used in the assay. Assay specificity was improved by the use of thyroxine (T4)-binding globulin as a second ligand-binding protein to decrease T4 and triiodothyronine (T3) cross-reactivity with the antibody. Double antibody and polyethylene glycol radioimmunoassays were compared. DIT present in the second antiserum shifted the double antibody assay standard curve and altered estimates of assay specificity and assay sensitivity. By using the polyethylene glycol system and butanol:ethanol extracts of serum, DIT was measured in human serum. In 35 apparently healthy young adult controls DIT levels averaged 156 ng/100 ml. Random DIT levels averaged 158 ng/100 ml in 11 untreated hyperthyroid patients and 84 ng/100 ml in 15 untreated primary hypothyroid patients. No diurnal pattern in DIT levels could be demonstrated. Thyroid-stimulating hormone administration led to a variable but small rise in DIT levels, but short term T3 suppression was not associated with a measurable fall in DIT concentrations. Paired serum samples from the carotid artery and thyroid vein of 10 euthyroid goiter patients and one patient with a toxic solitary adenoma all showed a positive transthyroidal gradient indicating the thyroidal release of DIT in each patient. Measurable DIT levels of 45, 47, 68, and 80 ng/100 ml, respectively, were found in four fasting athyrotic patients indicating that the thyroid is not the only source of serum DIT. (+info)
Sympathovagal imbalance in hyperthyroidism.
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We assessed sympathovagal balance in thyrotoxicosis. Fourteen patients with Graves' hyperthyroidism were studied before and after 7 days of treatment with propranolol (40 mg 3 times a day) and in the euthyroid state. Data were compared with those obtained in a group of age-, sex-, and weight-matched controls. Autonomic inputs to the heart were assessed by power spectral analysis of heart rate variability. Systemic exposure to sympathetic neurohormones was estimated on the basis of 24-h urinary catecholamine excretion. The spectral power in the high-frequency domain was considerably reduced in hyperthyroid patients, indicating diminished vagal inputs to the heart. Increased heart rate and mid-frequency/high-frequency power ratio in the presence of reduced total spectral power and increased urinary catecholamine excretion strongly suggest enhanced sympathetic inputs in thyrotoxicosis. All abnormal features of autonomic balance were completely restored to normal in the euthyroid state. beta-Adrenoceptor antagonism reduced heart rate in hyperthyroid patients but did not significantly affect heart rate variability or catecholamine excretion. This is in keeping with the concept of a joint disruption of sympathetic and vagal inputs to the heart underlying changes in heart rate variability. Thus thyrotoxicosis is characterized by profound sympathovagal imbalance, brought about by increased sympathetic activity in the presence of diminished vagal tone. (+info)
Long-term thyroxine administration increases heat stress protein-70 mRNA expression and attenuates p38 MAP kinase activity in response to ischaemia.
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The present study was undertaken to investigate heat stress protein (HSP)-70 mRNA induction and p38 MAP kinase (MAPK) activity in response to ischaemic stress in the hyperthyroid rat heart. L-Thyroxine (T(4)) (25 microg/100 g body weight) was administered to Wistar rats for 2 days (THYRacute) or 14 days (THYR), while animals treated similarly with normal saline served as controls (NORMacute and NORM). In addition, abdominal aortic banding was performed in another group of rats to produce constriction-induced hypertrophy (HYP), while sham-operated (SOP) animals served as controls. Isolated rat hearts were perfused in a Langendorff mode. Hearts from NORMacute (n=6), THYRacute animals (n=8), NORM (n=6), THYR (n=6), SOP (n=5) and HYP (n=7) animals were subjected to 20 min of zero-flow global ischaemia followed by 45 min of reperfusion. HSP70 mRNA expression and phosphorylated p38 MAPK protein expression were detected in response to ischaemia and protein kinase C-epsilon (PKCepsilon) protein expression was detected at baseline. Thyroid hormones were measured in plasma. Long-term T(4) administration and aortic constriction resulted in the development of cardiac hypertrophy. Thyroid hormones were increased in both THYR and THYRacute as compared with normal groups (P<0.05). HSP70 mRNA induction was increased 2.3-fold in THYR as compared with NORM hearts (P<0.05), whereas there was not any difference between THYRacute and NORMacute hearts (P>0.05). Phosphorylated p38 MAPK protein expression was 2.2-fold more in NORM than in THYR hearts (P<0.05), but it was not different between NORMacute and THYRacute hearts (P>0.05). HSP70 mRNA induction was 1.8-fold greater in HYP than in SOP hearts (P<0.05), whereas phosphorylated p38 MAPK protein expression was similar between the two groups (P>0.05). PKCepsilon protein expression at baseline was 1.7-fold more in NORM than in THYR hearts (P<0.05), and not different between NORMacute and THYRacute hearts (P>0.05) as well as HYP and SOP hearts (P>0.05). This study shows that HSP70 mRNA expression is increased, whereas p38 MAPK activation is attenuated in response to ischaemia in long-term T(4)-treated rat hearts as compared with normal and acute hyperthyroid hearts. (+info)
Induction of autoimmune hypothyroidism and subsequent hyperthyroidism by TSH receptor antibodies following subacute thyroiditis: a case report.
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A 45 year-old man had a typical episode of subacute thyroiditis with tender goiter, depressed radioiodine uptake (RAIU) and elevated erythrocyte sedimentation rate. The titer of TSH binding inhibitor immunoglobulin (TBII), which had been 8.6% at initial presentation, rose to 14.9% in 2 weeks. TBII consisted of high titers (94%) of TSH stimulation-blocking antibodies (TBAb) and negative thyroid stimulating antibodies (TSAb). About 2 months after the first visit, TBII titers had risen to 48.9% and were persistently elevated for 5 months with high TBAb activity. The patient developed hypothyroidism with a maximum serum TSH level of 54.5 microU/ml. TBII and TBAb titers then gradually decreased, and the patient spontaneously recovered from hypothyroidism. Eighteen months after the episode of subacute thyroiditis, he became hyperthyroid with elevated TSAb and negative TBAb values. Doppler ultrasonography showed increased blood flow in the thyroid, and RAIU at 24 h was 53%. He was treated with antithyroid drugs, and soon became euthyroid. This case indicates that subacute thyroiditis can induce thyroid autoimmunity, and that the character of TSH receptor antibodies (TSHRAb) in these patients can change thereby modifying their thyroid function. (+info)