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Biomedical subjects

A Melander

Publications and source records attributed to A Melander.

At least 217 records · Page 12Linked to original sources

Divergent changes of serum 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine in patients with acute myocardial infarction.

The serum levels of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3, rT3), thyroxine-binding globulin and thyroid-stimulating hormone have been monitored in 13 patients with acute myocardial infarction. The major changes recorded were a transient decrease in T3 and a transient increase in rT3. They reached a nadir and a peak, respectively, within three days. A conceivable explanation for these alterations is that the monodeiodination of T4 is diverted from the activating pathway (T4 to T3) to the inactivating pathway (T4 to rT3).

Acute Disease↗

Effects of dexamethasone, desoxycorticosterone, and ACTH on serum concentrations of thyroxine, 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine.

The effects of a pure glucocorticoid, dexamethasone, and a pure mineralocorticoid, desoxycorticosterone, on the serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5'-triiodothyronine (reverse T3, rT3) were compared both in healthy subjects and in athyreotic T4-substituted patients. In addition, the effect of exogenous ACTH was examined in healthy subjects. Both in healthy subjects and in T4-substituted athyreotic patients, administration of a single oral dose of dexamethasone caused a rapid and sharp decrease in the serum concentration of T3, and a corresponding increase in the serum concentration of rT3. The T4 concentration was not changed. A single oral dose of desoxycorticosterone evoked no significant changes in the serum concentrations of T3, rT3, or T4 either in healthy subjects or in T4-substituted athyreotic patients. Like dexamethasone, ACTH (two i.v. injections of 60 IU each, at a 6-hour interval) evoked a serum T3 reduction and a serum rT3 increase. Hence, it appears that both endogenous and exogenous glucocorticoids, but not mineralocorticoids, may partially divert the deiodination of T4 from the activating (T4 lead to T3) to the inactivating (T4 leads to rT3) pathway.

Adrenal Cortex Hormones↗

Bioavailability of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): interindividual variation and influence of food intake.

The influence of food intake on the bioavailability of three analgesic compounds--propoxyphene chloride, acetyl salicylic acid and phenazone--in a combination tablet, Doleron, has been examined in eight healthy volunteers. A single oral dose was given both on an empty stomach and together with a standardized breakfast meal. The plasma concentrations of propoxyphene, its major metabolite norpropoxyphene, salicylic acid and phenazone were determined by mass fragmentography, spectrofluorimetry and gas chromatography. Concomitant food intake had no consistent influence on the bioavailability of any of the components. Hence, doleron may be taken together with meals as well as between meals. Large interindividual variations in propoxyphene and phenazone concentrations were found, indicating that an optimal effect will not always be obtained by standard doses.

Adult↗

Secretion of thyroxine, 3,5,3'-triiodothyronine and 3,3'5'-triiodothyronine in euthyroid man.

The secretion of iodothyronines from the normal human thyroid gland was assessed by radioimmunoassay analyses of the concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (reverse T3, rT3) in thyroid venous and peripheral venous blood. The subjects studied were euthyroid patients undergoing parathyroid surgery. Measurements were carried out both under apparently normal conditions, following peroral T3 pre-treatment, and before and after acute administration of TSH into a thyroid artery. In the control subjects, significant gradients between thyroid venous and peripheral venous concentrations were recorded both for T4, T3 and rT3, suggesting that all three iodothyronines are secreted by the normal human thyroid. T3 pre-treatment seemed to reduce this secretion, and acute administration of TSH promoted rapid, marked, and concomitant increments in the thyroid venous concentrations of all three iodothyronines. Hence, it appears that not only T4 but also T3 and rT3 are secreted by the normal human thyroid gland, and that TSH stimulates the secretion of all three iodothyronines. On the other hand, calculations of the relative secretion rates uielded the relation T4:T3:rT3 as 85:9:1. This indicates that, in euthyroid subjects, most of T3, and almost all of rT3, is produced by extrathyroidal conversion of T4 and not by direct thyroidal secretion.

Adult↗

Divergent effects of 6-propylthiouracil on 3,3',5'-triiodothyronine (RT3) serum levels and in man.

The effect of 6-propylthiouracil (PTU) on the peripheral conversion of thyroxine (T4) to 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (reverse T3 rT3) was investigated by assessments of the concentrations of T4 T3 and rT3 in peripheral venous blood from T4-treated healthy volunteers given PTU, 4 X 150 mg daily. Within on day of PTU administration, serum T3 concentrations were reduced, and those of rT3 enhanced. These deviations lasted as long as PTU was given (five days), and there was a rapid return towards normal within one day after PTU administration ceased. It seems probable that, in man, PTU can evoke a diversion of T4 monodeiodination, less being converted to the metabolically active T3 and more to the metabolically inactive rT3. It is ppossible that the rapidity whereby PTU can reduce T3 levels can offer an advantage in the treatment of hyperthyroidism.

Female↗

Stimulation of peripheral T3 formation by oral but not by intravenous glucose administration in fasted subjects.

Fasting is known to promote a shift in the conversion of thyroxine (T4), more being deiodinated to an inactive form, reverse triiodothyronine (rT3), and less to active triiodothyronine (T3). The mechanism behind this change is not known, but it has recently been demonstrated that the proportion of dietary carbohydrates influences the serum concentration of T3 and rT3. Therefore, it is possible that the deiodination of T4 is subordinated to gastroenterohepatic regulation. To explore this possibility, we administrated glucose by the oral or the intravenous route to volunteers, who had been fasted for 48 h. It was found that glucose normalized the low fasting T3 concentrations only after oral administration. This supports the assumption that some gastro enterohepatic factor participates in the regulation of T3 formation.

Administration, Oral↗

Inhibition by somatostatin of mouse thyroid activity following stimulation by thyrotrophin, isoprenaline and dibutyryl cyclic-AMP.

The recent discovery of somatostatin-containing cells within the thyroid gland infers that somatostatin may influence thyroid activity. This possibility was investigated by measurements of radio-iodine release in mice pre-treated with 125I and T4. The animals were treated with TSH, isoprenaline or dibutyryl-cyclic AMP with and without concomitant injection of somatostatin. It was found that somatostatin reduced the blood 125I increase in response to each of the three thyroid-stimulating agents. The elimination rates of 125I-labelled T4 and T3 were unaffected by somatostatin. The observations suggests that somatostatin may participate in the regulation of thyroid hormone secretion, by an inhibitory effect exerted within the thyroid gland.

Animals↗

Bioavailability of oxazepam: absence of influence of food intake.

The possible influence of food intake on the bioavailability of the anxiolytic drug oxazepam was assessed in eight healthy volunteers taking a single dose of the drug both on an empty stomach and together with a standardized breakfast meal. The serum concentrations of oxazepam were determined by gas chromatography on samples obtained before, and at numerous occasions up to 48 hours after drug administration. The results indicate that concomitant food intake has no essential influence on the bioavailability of oxazepam.

Adolescent↗

Reduction of isoniazid bioavailability in normal men by concomitant intake of food.

The influence of food intake on the bioavailability of isoniazid (INH) has been examined in nine healthy male volunteers. INH was administered as a single oral dose, both in fasting state and together with a standardized breakfast. Numerous venous blood samples were obtained 5 min-6 hours after the INH ingestion, and the concentrations of unmetabolized INH in serum were assessed by spectrophotometry. The observations indicate that both the peak concentration and the total amount of INH absorbed are greatly reduced when the drug is ingested together with food. Hence it is recommended that, in the treatment of tuberculosis with INH, the drug should be given on an empty stomach. The data may also have some bearing on the use of INH for assessing acetylation rates and estimating dosages of hydralazine and related drugs.

Administration, Oral↗

Blood levels of 3,5,3'-triiodothyronine and thyroxine: differences between children, adults, and elderly subjects.

The serum levels of 3,5,3'-triiodothyronine (T3) and thyroxine (T4) in children, adolescents, adults, and elderly subjects have been measured by radioimmunoassays. It was found that while the T4 levels were essentially equal in all age groups examined, the T3 levels were markedly different. In children and adolescents (1-15 years), high values were recorded; indeed, they exceeded the upper normal limit in adults (20-80 years). From the age of 20, the T3 levels remained unaltered until the age of 80, after which there was a further reduction, to values approaching the lower normal limit for T3 in middle-aged subjects. The findings emphasize that separate normal values must be established for different age groups, in order to avoid diagnostic misinterpretations and therapeutic failures.

Adolescent↗

On the influence of concomitant food intake on sulfonamide bioavailability.

The influence of food intake on the bioavailability of a frequently used short-acting sulfonamide, sulfaisomidine (Elkosin), has been examined in eight healthy volunteers. The drug was administered as a single oral dose, both on an empty stomach and together with a standardized breakfast. Numerous venous blood samples were drawn for the first eight hours after ingestion of the drug, and the concentration of unmetabolized sulfonamide in serum was assessed by spectrophotometry. The observations indicate that concomitant food intake alters neither absorption rate, peak concentration, time to reach peak concentration, elimination rate, nor total amount of sulfonamide reaching the general circulation. Thus, the absorption of orally administered sulfaisodimidine is not at all affected by concomitant intake of food. This finding contrasts with previous observations on some other sulfonamides, and it may signify a therapeutic advantage of sulfaisodimidine. In addition, the amount absorbed showed only a little interindividual variation. This suggests that the use of standardized size and interval of sulfaisodimidine dosage can be recommended. The present findings emphasize that conclusions about the absorption of a certain drug should not be derived from studies with other, albeit chemically related, compounds.

Adolescent↗

Sympathetic innervation of the thyroid: variation with species and with age.

Fluorescence histochemistry was used to study the sympathetic innervation of the thyroids from adult individuals of six different species; mouse, rat, hamster, dog, sheep, and pig. In addition, thyroids from very young rats and from very old mice were examined. Generally, thyroidal sympathetic, adrenergic nerve terminals were found not only as a network around vessels, but also as single terminals between, and sometimes around, follicles. Interfollicular terminals were numerous in thethyroids of adult mice, sheep and hamsters, but they were few in the thyroids of adult rats and dogs, and even fewer in the porcine thyroid. In contrast to the findings in thyroids from adult mice and rats, several interfollicular terminals were found in thyroids from very young rats while very few such terminals were detected in the thyroids from very old mice. The observations suggest that there is a pronounced interspecies variation in the number of thyroidal interfollicular sympathetic nerve terminals and that, at least in the rat and the mouse, there is also a variation with age. Since, in mice, sympathetic activation appears to induce thyroid hormone secretion by a direct action of norepinephrine released from intrathyroidal sympathetic fibers, the recorded variations are presumed to have functional importance.

Aging↗

Beta2-adrenergic stimulation of thyroid hormone secretion.

The influence on thyroid hormone secretion of the nonselective beta-adrenergic stimulant isoproterenol (IPNE), of a selective beta1-adrenergic stimulant, 1-isopropylamino-3-(2-thiazoloxy)-2-propanol (ITP), and of a selective beta2-adrenergic stimulant, terbutaline, was investigated in mice. A combination of light microscopy (colloid droplet formation) and bioassay (blood radioiodine--BRI--measurements) was used. IPNE and terbutaline induced formation of colloid droplets and increased BRI levels, whereas ITP was ineffective. The responses to IPNE and terbutaline were abolished or reduced by pretreatment with L-propranolol, but were not inhibited for pretreatment with D-propranolol or phentolamine. The results indicate that secretion of thyroid hormone can be induced through the mediation of beta2-adrenergic receptors.

Adrenergic beta-Agonists↗

Exocytosis of protein into the thyroid follicle lumen: an early effect of TSH.

As shown in a preceding paper, only exocytotic vesicles conveying newly synthesized protein to the follicle lumen remain in the apical part of rat thyroid follicle cells following elimination of TSH secretion. In the present paper the effect of TSH on these exocytotic vesicles was investigated. TSH secretion was suppressed by administration of thyroxine for 2 days. In the electron microscope administration of TSH was seen to induce well-known signs of endocytosis, such as formation of pseudopods and colloid droplets. In addition, a previously unrecognized change was noted, namely a progressive decrease in the number of exocytotic vesicles. At 5 min after TSH the number was obviously reduced and at 20 min less than 10% of the original number of vesicles remained. Quantitative electron microscopic autoradiography after administration of [3H]leucine showed that TSH caused, concomitant with the disappearance of vesicles, a transfer of radioactivity from the apical region of the follicle cell to the periphery of the follicle lumen. The distribution of labeled protein in thyroid subcellular fractions was studied 1.5 h after administration of [14C]leucine. At 5 min after administration of TSH there was an increase of protein-bound label in the supernatant fraction, containing the luminal colloid, and a corresponding decrease of label in the particle fraction which contained most of the cell organelles, including the exocytotic vesicles. This TSH-induced redistribution of labeled proteins was more pronounced at 10 min and still more at 20 min and appeared to be dose-dependent. These observations taken together are considered to justify the conclusion that TSH induces transfer of newly synthesized protein from the follicle cells to the follicle lumen by exocytosis (i.e., emptying of specific apical vesicles). It is suggested that a causal and functional interrelation may exist between the exocytotic and endocytotic processes.

Animals↗

Influence of histamine- and 5-hydroxytryptamine-containing thyroid mast cells on thyroid blood flow and permeability in the rat.

The possible significance of thyroid mast cells in the regulation of thyroid blood flow and capillary permeability was investigated in rats whose TSH secretion had been eliminated by exogenous T4. Mast cells were identified by their abundance of metachromatic granules, and their content of histamine and 5-hydroxytryptamine (5-HT) was examined by fluorescence histochemistry. Thyroid histamine levels were determined by fluorometry. The tissue uptake of 86Rb was used as an indicator of blood flow and permeability. Numerous histamine- and 5-HT-containing mast cells were found within the thyroid and in connective tissue adjacent to the thyroid, whereas juxtathyroidal muscle tissue was virtually devoid of mast cells. Administration of compound 48/80 evoked a prompt depletion of 5-HT, histamine and metachromatic granules from thyroid mast cells, and a concomitant increase in the thyroidal uptake of 86Rb. The 86Rb uptake by juxtathyroidal muscle tissue was unaffected. Exogenous 5-HT and histamine both induced prompt increments in thyroidal 86Rb uptake, and 5-HT also stimulated 86Rb uptake in juxtathyroidal muscle tissue. TSH, previously shown to induce a gradual amine release from mast cells within, but not outside, the thyroid, evoked a gradual increase in thyroidal, but not in muscular, uptake of 86Rb. The findings support the concept that, in the rat, histamine and/or 5-HT, released from intrathyroidal mast cells by TSH, stimulate thyroid blood flow and/or permeability.

Animals↗