Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven patients with Graves' disease were treated with guanadrel sulfate and observed for changes in neuromuscular and cardiovascular manifestations. No notable changes in pulse rate or muscle strength were detected in either these patients during a three-day pretreatment period or in five control patients with Graves' disease receiving placebo for six days. Thyroid hormone levels were not altered by seven days of guanadrel sulfate therapy (5 to 20 mg orally every six hours), and no adverse side effects were encountered. Mean supine resting pulse fell from 102 +/- 6 (mean +/- SEM) to 90 +/- 3 beats per minute (P less than .02). The patients' proximal and distal muscle strengths were initially decreased, when compared with healthy subjects, and improved substantially with guanadrel therapy. We conclude that guanadrel sulfate may be useful in the symptomatic management of patients with thyrotoxicosis.
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PMID:Effects of guanadrel on patients with thyrotoxicosis. 58 Aug 63

We have studied by flow cytometric analysis the antigen specific activation of CD4+ (helper/inducer) T lymphocytes by purified human thyroid peroxidase (TPO). Peripheral blood mononuclear cells were obtained from 26 patients with Graves' disease (GD), 16 with Hashimoto's thyroiditis (HT), 7 with nontoxic nodular goiter (NG), and 14 normal subjects (N). Cells were cultured for 7 days in the presence or absence of TPO at final concentrations of 3, 30, and 300 ng/mL. When harvested, cells were reacted with an FITC-conjugated anti-CD4 and a PE-conjugated anti-HLA-DR murine monoclonal antibodies. The percentage of HLA-DR+ CD4+ cells (activated CD4+ cells) was determined by a flow cytometer. In the absence of TPO, CD4+ cells had been activated without any specific stimulant. This is known as the autologous mixed lymphocyte reaction (AMLR). In the AMLR, CD4+ cells from GD and HT were less activated compared to those from NG and N. Results of TPO-specific activation were expressed as an incremental increase of activated CD4+ cells (II) (percentage of activated CD4+ cells cultured with TPO minus percentage of activated CD4+ cells cultured without TPO). II of N, GD, HT, and NG were 0.37 +/- 0.21, 2.20 +/- 0.45,** 2.0 +/- 0.66,* and 0.35 +/- 0.27 (mean +/- SEM), respectively (**p less than 0.01; *p less than 0.05 vs N). When patients were further subdivided, the highest mean II was found in patients with hyperthyroid GD (p less than 0.01), followed by euthyroid HT (p less than 0.05) and euthyroid GD (p less than 0.05), however there was no significant difference between hypothyroid HT and N. In conclusion (1) AMLR reactivity of CD4+ cells from GD and HT was impaired, (2) however, CD4+ cells from both GD and HT were significantly more induced by TPO compared to N, and (3) this induction depends, in part, on the in vivo thyroid status.
Thyroid 1991
PMID:Studies of CD4+ (helper/inducer) T lymphocytes in autoimmune thyroid disease: demonstration of specific induction in response to thyroid peroxidase (TPO) in vitro and its relationship with thyroid status in vivo. 168

We tested the hypothesis that the decrease in the thyroid state, with age, contributes to the age-related increase in myocardial responsiveness to cardiac glycosides. Thyroid hormone levels (reflecting the thyroid state): total T4 (microgram/dl) and total T3 (ng/dl) in the 3 groups of guinea pigs were (mean +/- SEM): adults (3 months old): less than 1.0 and 22.6 +/- 1.1; euthyroid newborns (0-5 days old): 3.9 +/- 0.4 and 56.5 +/- 11.9; hypothyroid newborns, (0-5 days old): 1.5 +/- 0.3 and 26.5 +/- 9.8. In euthyroid newborns, T4 and T3 levels were significantly higher than in adults (p less than 0.01 for T4 and p less than 0.05 for T3) and in hypothyroid newborns (p less than 0.05). Isometric twitch was recorded from right ventricular papillary muscles by means of a force transducer. Ouabain 10(-6) M increased isometric twitch tension in adults (tension = 0.66 +/- 0.18 g/mm2) by 123.6 +/- 18.2%, in euthyroid newborns (tension = 0.19 +/- 0.04 g/mm2) by 83.6 +/- 14.5%, and in hypothyroid newborns (tension = 0.12 +/- 0.01 g/mm2) by 170.9 +/- 33.8% (p less than 0.01). Ouabain dose-response curve in the range of 10(-7) M-0.5 x 10(-5) M was significantly different (compared by two-way ANOVA) between euthyroid newborns and hypothyroid newborns (p less than 0.01), and between euthyroid newborns and adults (p less than 0.01). Toxic effects of ouabain reflected by the generation of aftercontractions were also age related and were augmented by hypothyroidism in newborns.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of thyroid state in age-dependent cardiac effects of ouabain in guinea pigs. 181 26

We have previously described that sodium ipodate (500 mg/day, p.o.) is effective in normalizing serum T3 and T4 levels in most patients with Graves' hyperthyroidism. In this study, we examined serum T3, T4, and rT3 levels in 14 hyperthyroid patients with Graves' disease during treatment with a lower dose (500 mg, every other day, p.o.) of sodium ipodate for a period of 3-30 weeks (mean 15.5 weeks). Three types of responses were observed. In group I (4 patients), both serum T3 and T4 were in the normal range at the end of treatment [baseline: mean +/- SEM T3, 6.8 +/- 0.96 nmol/L (normal 0.92-3.0)] and T4 [256 +/- 44 nmol/L (normal 62-167); post-ipodate: T3, 2.0 +/- 0.46 nmol/L and T4 107 +/- 28 nmol/L]. In group II (n = 5), either serum T3 (3 patients) or serum T4 (2 patients) did not become normal (baseline: T3 7.7 +/- 1.1 and T4 228 +/- 3.9; post-ipodate: T3 2.9 +/- 0.57 and T4 188 +/- 27 nmol/L). In group III (5 patients), neither serum T3 nor serum T4 returned to normal following ipodate treatment (baseline: T3 11.9 +/- 1.8 and T4 260 +/- 23; post-ipodate: T3 7.5 +/- 0.49 and T4 322 +/- 17 nmol/L). The mean serum rT3 concentration increased during ipodate treatment to a peak value of 100% above baseline and remained elevated (20-75% above baseline) throughout the study. Some improvement in hyperthyroidism was suggested by increase in body weight during ipodate treatment in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Thyroid 1991
PMID:Further studies on the long-term treatment of Graves' hyperthyroidism with ipodate: assessment of a minimal effective dose. 182 59

Amiodarone (Cordarone) has been proven to be useful in the management of atrial fibrillation. However, because of a large iodine content, this drug is not used in this complication of thyrotoxicosis. We previously have observed a greater fall in serum T3 and T4 concentrations in hyperthyroid patients treated with amiodarone and methimazole than with methimazole alone. In the present study, we determined whether the addition of amiodarone to propylthiouracil (PTU) could improve the levels of circulating thyroid hormones in hyperthyroid patients, and we assessed the release of iodide from amiodarone by measuring the 24 h urinary iodine excretion. Twelve hyperthyroid patients were treated either with PTU, 600 mg daily for 10 days (group PTU), or with amiodarone (A), 1200 mg daily for 3 days in addition to PTU (group A-PTU). Basal serum T4, T3, and rT3 concentrations (mean +/- SEM) were respectively 206 +/- 13 nmol/L, 5.13 +/- 0.8 nmol/L, and 81 +/- 7 ng/dL for group PTU and 238 +/- 39 nmol/L, 4.73 +/- 1.06 nmol/L, and 84 +/- 12 ng/dL for group A-PTU (NS). In group A-PTU, plasma amiodarone peaked on day 3 (mean +/- SEM: 0.48 +/- 0.11 mg/L), and urinary iodine reached 5.27 +/- 1.28 mg/day on day 5. The fall in serum T3 and the increase in serum rT3 concentrations were significantly greater in group A-PTU than in group PTU (ANOVA, p less than 0.05). In group A-PTU, the minimal serum T3 concentration was observed on day 5 of treatment (28 +/- 6% of the pretreatment values).(ABSTRACT TRUNCATED AT 250 WORDS)
Thyroid 1991
PMID:Effects of amiodarone on serum T3 and T4 concentrations in hyperthyroid patients treated with propylthiouracil. 184 29

Thyroid function parameters (triiodothyronine, thyroxine, reverse triiodothyronine, thyroid stimulating hormone, thyroglobulin) and thyroid binding globulin (TBG) were determined in sera of 64 women who had carried a normal pregnancy and delivered at term, as well as in sera of their newborns. Obtained results were compared to the findings of the same parameters in 28 women who delivered at term, but had been receiving gestanges 1 to 5 months prior to the delivery, and in their babies. In both groups, serum triiodothyronine (T3) levels were normal both in mothers and in their babies. Foetal serum reverse triiodothyronine (rT3) levels were higher (1.58 +/- 0.14, means +/- SEM) as compared to serum levels (0.36 +/- 0.04) of the mothers treated with gestagens; similar results were obtained in the mothers with normal pregnancy (0.41 +/- 0.03) and their babies (1.65 +/- 0.15, means +/- SEM). In 13 out of 64 (20%) women with normal pregnancy serum thyroxine (T4) was elevated in delivery at term, with no impact on the clinical course. Of 28 women who were treated with gestagens for 1 to 5 months only 4 had elevated serum T4 on the delivery. Using gestagens, according to our results, contributes to an increase of the newborn TBG levels (27.00 +/- 2.65; means +/- SEM) in a significant way (p less than 1.001) as compared to TBG of the newborn delivered after a normal pregnancy (21.40 +/- 2.55).
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PMID:Some extrathyroid regulatory mechanisms' aspects in thyroid humoral state at the delivery. 213 26

Thyroid hormones are known to modulate the concentrations of epidermal growth factor (EGF) in the mouse submandibular gland (SMG); this action is presumably mediated by the nuclear triiodothyronine receptor. To test the hypothesis that thyroid hormones act to increase SMG EGF concentrations by increasing the number of poly(A)+ -specific mRNA, poly(A)+ RNA was isolated from SMGs of neonatal mice which had been treated daily from birth through to 21 days of age with thyroxine (T4,0.4 microgram/g body weight). Poly(A)+ RNA also was extracted from SMGs of intact 21-day-old mice which had received vehicle alone. No significant differences in total nucleic acid, total RNA, or poly(A)+ RNA yields were noted between the two groups of animals. The isolated poly(A)+ RNAs from T4-treated and control mice were translated in an in vitro wheat germ system. Although no significant differences in efficiency of [35S]cysteine incorporation into trichloracetic acid precipitable material were noted between the two poly(A)+ RNA preparations, a significantly greater proportion of radioactivity was immunoprecipitable by anti-EGF antiserum in the translation medium derived from T4-treated mice (17.2 +/- 0.9%, mean +/- SEM) than in that of control mice (7.3 +/- 0.5%, P less than 0.001). Polyacrylamide gel electrophoresis of the immunoprecipitates (IMMP) revealed the presence of three radioactive bands with apparent relative masses (MrS) of 12,000, 9000, and 6000. The latter species comigrated with purified EGF, [125I]EGF, and an IMMP of a SMG extract. The translation product IMMPs following polyacrylamide gel electrophoresis were iodinated and digested with alpha-chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thyroxine increases neonatal mouse submandibular gland mRNA-directed synthesis of epidermal growth factor. 242 79

Thyroid hormones have been previously shown to alter cardiac electrophysiological and mechanical properties in humans and in experimental animals. To investigate electrophysiological mechanisms responsible for some of these alterations, we recorded action potentials and membrane currents from isolated ventricular myocytes obtained from euthyroid, hypothyroid and hyperthyroid guinea-pigs. Hyperthyroidism was induced by injecting 150 micrograms/kg triiodothyronine for 8-11 days, and hypothyroidism was induced by propylthiouracil treatment for 35-45 days. We found that the slow inward current, was increased by hyperthyroidism and decreased by hypothyroidism: in euthyroid, hyperthyroid and hypothyroid myocytes peak slow inward current was (mean +/- SEM): -1.08 +/- 0.06 nA, -1.83 +/- 0.18a nA and -0.64 +/- 0.07a nA, respectively (a, p less than 0.005). In addition, the membrane potential at which peak slow inward current occurred was modified by the thyroid state and in euthyroid, hyperthyroid and hypothyroid myocytes it was (mean +/- SEM): 4.8 +/- 0.7 mV, -1.8 +/- 1.6a mV and 11.0 +/- 1.4a mV, respectively. The outward rectifying current, was also affected by the thyroid state, and in euthyroid, hyperthyroid and hypothyroid myocytes, the amplitude at VM = +60 mV was (mean +/- SEM): 0.51 +/- 0.09 nA, 1.15 +/- 0.08a nA and 0.49 +/- 0.05 nA, respectively. a, p less than 0.001 compared to euthyroid myocytes. Intraperitoneal administration of a single dose of triiodothyronine to guinea-pigs, 2 h prior to the electrophysiological experiment, increased the slow inward current amplitude, as was seen with chronic hyperthyroidism, but had no significant effect on the outward current and on the action potential.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thyroid hormone modulates membrane currents in guinea-pig ventricular myocytes. 261 60

Thyroid function and ultrasonographically determined thyroid volume were investigated at regular intervals during pregnancy and the first postpartum year in 20 women without thyroid autoantibodies. Serum total thyroxine and total triiodothyronine levels were increased and free thyroxine index and free triiodothyronine index levels were decreased, whereas serum thyrotropin level was unaltered during pregnancy when compared with postpartum levels. Thyroid volume was increased during pregnancy with a mean variation of 30% between maximum values (24.1 +/- 2.2 ml, mean +/- SEM, thirty-sixth week of pregnancy) and minimum values (18.4 +/- 2.0 ml, 12 months post partum) (p less than 0.01). In conclusion, our study demonstrates a goitrogenic effect of pregnancy unexplained by alterations in thyroid function variables.
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PMID:Ultrasonographically determined thyroid size in pregnancy and post partum: the goitrogenic effect of pregnancy. 265 12

To gain insight into the mechanism of the altered carbohydrate metabolism in thyrotoxicosis, intravenous glucose tolerance tests (IVGTT) and pancreatic suppression tests (PST) were performed in hyperthyroid rats (0.1 mg/kg T4 X 5 days) to assess insulin secretion and action in vivo. Thyroid hormone injections significantly increased T4 levels (182.8 nM +/- 11.6 (SEM) versus 50.2 +/- 6.4; P less than 0.001) and baseline glucose concentrations (9.3 mM +/- 0.2 versus 7.1 +/- 0.2; P less than 0.001). Body weights, basal insulin concentrations, glucose concentrations during IVGTT, glucose disappearance rates and steady state plasma glucose levels (SSPG) were normal. Insulin concentrations during the glucose tolerance test and during the PST were significantly decreased. The metabolic clearance rate of insulin (ml/min/kg +/- SEM) was significantly (P less than 0.01) increased (54.4 +/- 3.5 versus 41.6 +/- 2.3) in the hyperthyroid rats. If the different baseline glucose values were subtracted from the glucose concentrations achieved during the 2 tests, both the glucose disappearance rate and the fall in SSPG levels were significantly enhanced in the T4-injected animals. Thus, in the hyperthyroid rat, insulin secretion is decreased, the clearance of insulin is increased and insulin sensitivity is either normal or possibly enhanced.
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PMID:Insulin secretion and action in the hyperthyroid rat. 286 1


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