Microsomal long-chain acyl-CoA thioesterase (carboxylesterase ES-4) is regulated by thyroxine. (9/1289)

Long chain acyl-CoA thioesterase activity is mainly located in microsomes after subcellular fractionation of liver from untreated rats. The physiological function and regulation of expression of this activity is not known. In the present study we have investigated the effect of thyroxine on expression of carboxylesterase ES-4, the major acyl-CoA thioesterase of liver microsomes. Thyroidectomy of rats decreased the palmitoyl-CoA thioesterase activity to about 25% of normal activity. This decrease was accompanied by similar decreases at the protein and mRNA levels (31% and 57%, respectively, of controls). Treatment with thyroxine completely reversed the effect of thyroidectomy and resulted in elevated levels in both thyroidectomized and control rats. For reasons of comparison we also studied the possibility that ES-10 and ES-2, two other members of the same gene family, are affected by thyroxine. ES-10 was not changed at the protein or mRNA level by any of the treatments, while ES-2 expression in liver was decreased by thyroxine treatment. The data shows that changes in activity and expression of ES-4 correlate to thyroxine status in the rat suggesting a physiological regulatory role by this hormone. Since thyroxine regulates the expression of lipogenic enzymes, these results are consistent with a function for this microsomal acyl-CoA thioesterase in fatty acid synthesis and/or secretion, rather than in oxidative degradation of fatty acids.  (+info)

The influence of hypothyroidism on wound healing. An experimental study. (10/1289)

An experimental study was performed to investigate the influence of hypothyroidism on wound healing. A state of severe hypothyroidism was induced initially by performing a total thyroidectomy on rat models; subsequently wounds were made by making long midline abdominal incisions and then suturing them. The parameters used to evaluate the process of wound healing of these incisions were the assay of type-I collagen, type-III collagen (procollagen peptide PIPC and P III P, each being the precursor of collagen), type-IV collagen, and hydroxyproline. The assays were repeated at specific times and compared to assays of similar parameters taken from a control group. In the state of hypothyroidism, a decrease was observed in type-IV collagen and hydroxyproline during the proliferative phase of wound healing. This indicated that the state of hypothyroidism constitutes an important factor in delaying wound healing.  (+info)

Calcimimetic compound NPS R-568 stimulates calcitonin secretion but selectively targets parathyroid gland Ca(2+) receptor in rats. (11/1289)

N-(3-[2-Chlorophenyl]propyl)-(R)-alpha-methyl-3-methoxybenzylamine (NPS R-568) is an orally active compound that activates Ca(2+) receptors on parathyroid cells and rapidly suppresses plasma levels of parathyroid hormone (PTH) and Ca(2+) (ED(50), 1 and 10 mg/kg, respectively). We now show that increased calcitonin secretion contributes to NPS R-568-induced hypocalcemia. In parathyroidectomized thyroid-intact rats in which normocalcemia was restored by PTH infusion, NPS R-568 rapidly reduced plasma Ca(2+) levels, indicating that decreased PTH secretion was not solely responsible for the hypocalcemia seen in normal animals. NPS R-568 decreased plasma Ca(2+) levels in thyroidectomized parathyroid-intact rats, but the rate of onset of hypocalcemia was slower than in controls. In contrast, NPS R-568 had no effect on plasma Ca(2+) levels in PTH-infused, thyroparathyroidectomized rats, providing evidence that increased calcitonin secretion caused the hypocalcemia in PTH-infused parathyroidectomized rats. NPS R-568 rapidly increased plasma calcitonin levels to a peak at 10 to 20 min after oral dosing (ED(50) 40 mg/kg). NPS R-568 did not affect the rate of disappearance of (45)Ca from blood, indicating that hypocalcemia resulted from decreased influx of Ca(2+) into the circulation and not from increased efflux. This suggests that NPS R-568-induced hypocalcemia resulted solely from reduced efflux of Ca(2+) from bone after increased calcitonin and reduced PTH secretion. Thus, NPS R-568 causes hypocalcemia by activating Ca(2+) receptors on C cells and parathyroid cells; however, NPS R-568 is about 40 times more potent in reducing PTH levels than in increasing calcitonin levels.  (+info)

Prognostic variables of papillary thyroid carcinomas with local invasion. (12/1289)

To evaluate the significance of the extrathyroid extension (ETE) of papillary thyroid carcinoma at the time of diagnosis and the prognostic variables of patients, we retrospectively reviewed 1,013 thyroid cancer patients. Of the 741 papillary thyroid cancer patients, 466 (62.9%) were categorized in clinical stage I and 114 (15.4%) were categorized in clinical stage III. Of the 114 patients in clinical stage III, 81 were female (mean age 44.4 +/- 15.7 years) and 33 were male (mean age 46.9 +/- 18.1 years). Of the clinical stage III patients, 104 patients received post-operative radioactive iodide (131I) therapy while 22 patients received external radiotherapy in the neck and upper mediastinum area post-operatively. In the study, age, gender, 131I accumulated dose, post-operative serum thyroglobulin (Tg) levels, and survival rate were demonstrated to be statistically significant in the groups with no recurrence and recurrence after treatment. The average follow-up period of these patients was 6.0 years. During this follow-up period, 11 patients expired. Eight died of thyroid cancer (7.0%) and 3 died of intercurrent diseases including asthma, renal cell carcinoma and propranolol overdose. Four of the 8 patients (50%) died of airway obstruction due to cancer cell invasion. Another 4 died of distant metastases, including 2 patients with skull metastases and brain invasion. The 5- and 10-year survival rates were 0.981 and 0.956 in clinical stage I and 0.923 and 0.843 in clinical stage III, respectively. In conclusion, the survival rate of the ETE of papillary thyroid cancer was lower when compared with stage I, especially in older male patients with higher post-operative serum Tg levels.  (+info)

A case of amyloid goiter secondary to Crohn's disease. (13/1289)

We herewith report a case of amyloid goiter secondary to Crohn's disease. The patient had been diagnosed as having Crohn's disease at the age of 15, and underwent right hemicolectomy at age 20. When he was 26 years old he complained of swelling of the anterior neck. Both TSH and thyroid hormones were within the normal range, and anti-thyroglobulin and anti-microsomal antibodies were negative. Only thyroglobulin was noticeably above the normal range. During the next year his goiter enlarged further and because he had a feeling of pressure he underwent total thyroidectomy. The presence of amyloid A protein in his surgical specimen led to the diagnosis of amyloid goiter. Although most cases of secondary amyloidosis are known to develop in neoplasms or chronic inflammatory diseases, our patient had no illness other than Crohn's disease. Perusal of literature revealed that Crohn's disease is rarely a cause of amyloid goiter.  (+info)

Symptomatic versus asymptomatic papillary thyroid microcarcinoma: a retrospective analysis of surgical outcome and prognostic factors. (14/1289)

Although the mortality rate associated with papillary microcarcinoma (PMC) of the thyroid generally is very low, some patients present with bulky nodal metastasis or distant metastasis and have an unfavorable prognosis. We retrospectively reviewed clinical aspects, surgical treatment and outcome of 178 patients with PMC in an attempt to determine the prognostic factors. The cause-specific 10-year survival rate was 96%. Three of four patients who showed signs of distant metastasis during the postsurgical period died of the disease, and another died of local recurrence. The most significant prognostic factors were the presence of clinically apparent lymph-node metastasis and hoarseness due to recurrent nerve palsy at the time of diagnosis. All distant metastases and cancer-specific deaths occurred in the 30 patients with symptomatic PMC who had either cervical lymphadenopathy, recurrent laryngeal nerve palsy or both. The 148 patients who had neither symptom had a distinctly favorable outcome. Total thyroidectomy followed by radioactive iodine treatment did not improve the final outcome in patients with symptomatic PMC. We conclude that patients with asymptomatic PMC can expect a truly favorable outcome, but some of those with symptomatic PMC may fall within a high-risk group of patients who do not benefit from aggressive treatment.  (+info)

T(3) stimulates resting metabolism and UCP-2 and UCP-3 mRNA but not nonphosphorylating mitochondrial respiration in mice. (15/1289)

The molecular basis for variations in resting metabolic rate (RMR) within a species is unknown. One possibility is that variations in RMR occur because of variations in uncoupling protein 2 (UCP-2) and uncoupling protein 3 (UCP-3) expression, resulting in mitochondrial proton leak differences. We tested the hypothesis that UCP-2 and -3 mRNAs positively correlate with RMR and proton leak. We treated thyroidectomized and sham-operated mice with triiodothyronine (T(3)) or vehicle and measured RMR, liver, and skeletal muscle mitochondrial nonphosphorylating respiration and UCP-2 and -3 mRNAs. T(3) stimulated RMR and liver UCP-2 and gastrocnemius UCP-2 and -3 expression. Mitochondrial respiration was not affected by T(3) and did not correlate with UCP-2 and -3 mRNAs. Gastrocnemius UCP-2 and -3 expression did correlate with RMR. We conclude 1) T(3) did not influence intrinsic mitochondrial properties such as membrane structure and composition, and 2) variations in UCP-2 and -3 expression may partly explain variations in RMR. One possible explanation for these data is that T(3) stimulates the leak in vivo but not in vitro because a posttranslational regulator of UCP-2 and -3 is not retained in the mitochondrial fraction.  (+info)

Good prognosis in thyroid cancer found incidentally at surgery for thyrotoxicosis. (16/1289)

An analysis of the outcome of thyroid carcinoma incidentally discovered in patients undergoing surgery for hyperthyroidism is presented. Among 986 patients with differentiated thyroid cancer, 23 had presented with symptoms and signs of hyperthyroidism. Graves' disease was diagnosed in 11, multinodular goitre in eight and toxic adenoma in four. Following thyroidectomy, histology revealed papillary (18), follicular (four) and Hurthle cell (one) carcinoma. Tumour size ranged from 4 mm to 5.5 cm, multifocality was detected in three patients, and lymph node involvement in one. Two patients (one with associated Graves' disease, one with multinodular goitre) relapsed locally and required further surgery; one developed distant metastases and died 7 years after initial presentation. Two patients died of unrelated causes; the remaining 20 patients are alive and well with a median follow-up of 16 (1-34) years. Differentiated thyroid cancer found incidentally at surgery for hyperthyroidism has a good prognosis.  (+info)