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Biomedical subjects

P Hedner

Publications and source records attributed to P Hedner.

At least 55 records · Page 3Linked to original sources
PubMed1983

Dyslipoproteinaemia in hypothyroidism of pituitary origin: effects of L-thyroxine substitution on lipoprotein lipase, hepatic lipase, and on plasma lipoproteins.

We have studied the effects of L-thyroxine substitution on lipoprotein concentrations, on the activities of lipoprotein lipase (LPL) and hepatic lipase (HL), and on the elimination rate of exogenous triglyceride in a homogeneous group of patients with hypothyroidism of pituitary origin. All were deficient of sex hormones but not of corticosteroids during the observation period. Before treatment total plasma cholesterol, LDL cholesterol, and triglyceride levels were significantly higher than in a euthyroid control group but not as high as in patients with overt primary hypothyroidism. The activities of LPL and HL were also intermediate between those of euthyroid and overt primary hypothyroid subjects, and there was a significant reduction of the elimination rate of exogenous triglyceride. No changes were found for HDL cholesterol levels. When the patients with secondary hypothyroidism were compared to patients with primary hypothyroidism, matched for thyroid function levels, age, sex, and weight, there were no differences with regard to plasma lipoprotein concentrations or post-heparin lipase activities. In 3 patients with secondary hypothyroidism the lipoprotein profiles were studied by zonal ultracentrifugation and found to agree well with changes observed in primary hypothyroidism. L-thyroxine substitution produced a normalization of lipase activities and lipoprotein concentrations in patients with secondary hypothyroidism. We conclude that there are no fundamental differences in the disturbances of the lipoprotein metabolism in primary and secondary forms of hypothyroidism.

Adolescent↗
PubMed1983

Relations between thyroid function, hepatic and lipoprotein lipase activities, and plasma lipoprotein concentrations.

Lipoprotein concentrations and activities of lipoprotein lipase (LPL) and hepatic lipase (HL) were measured in 70 subjects with thyroid function ranging from overt hypothyroidism over subclinical hypothyroidism and euthyroidism to hyperthyroidism. In parallel with serum T3 (S-T3) concentrations increasing from low in hypothyroidism to high in hyperthyroidism there were gradually higher HL activities over the full spectrum of thyroid function, accompanied by decreasing levels of total and low density lipoprotein (LDL) cholesterol. High density lipoprotein (HDL) cholesterol was lower (P less than 0.05) in hyperthyroidism than in euthyroidism but not significantly changed in the hypothyroid groups. HL was correlated to S-T3 (r = 0.77, P less than 0.001), LDL cholesterol to log S-T3 (r = -0.76, P less than 0.001), and LDL cholesterol to log HL (r = -0.55, P less than 0.001). The activity of LPL was decreased (P less than 0.001) in overt hypothyroidism compared to euthyroidism but, in contrast to HL, the activity of LPL was not increased in hyperthyroidism. The plasma triglyceride (P-TG) concentration was elevated (P less than 0.01) in overt hypothyroidism but not significantly changed in subclinical hypothyroidism or in hyperthyroidism. The LPL activity was correlated to log S-T3 (r = 0.45, P less than 0.001), P-TG to log S-T3 (r = -0.37, P less than 0.01) and P-TG to log LPL activity (r = -0.71, P less than 0.001). Our results demonstrate that thyroid hormones influence HL and LPL activities in different ways, suggesting different mechanisms of action. Changes in HL activity seem to be an important mechanism for the disturbance of cholesterol metabolism in thyroid dysfunction while the thyroid hormone influence on LPL seems to be of importance mainly for the disturbance in triglyceride metabolism.

Adult↗
PubMed1982

Effects of thyrotrophin stimulation for two hours on mouse thyroid cyclic AMP levels in vivo and in vitro.

A thyrotrophin (TSH) stimulation in vivo in mice for 2 h, reflected by continuously increasing plasma triiodothyronine (T3) levels, was associated with an increase in the thyroid content of cyclic AMP (cAMP) during the first 25 min of stimulation; thereafter the level rapidly declined. A similar pattern of the cAMP response was found when mouse thyroid tissue was stimulated by TSH in vitro for 2 h. This is an in vivo demonstration of a type of cAMP response to prolonged hormonal stimulation that has been observed in several in vitro systems including thyroid tissue, generally referred to as hormone induced desensitization of adenyl cyclase. The present results indicate that the phenomenon is not confined to in vitro conditions but can be demonstrated also in vivo, and support the representativeness of in vitro experiments in this respect.

Animals↗
PubMed1982

Topical and systemic glucocorticoid potencies of budesonide and beclomethasone dipropionate in man.

Topical anti-inflammatory (cutaneous "vasoconstriction") and systemic glucocorticoid (depression of plasma cortisol and changes in differential WBC count) potencies of the two glucocorticoids budesonide and beclomethasone dipropionate (BDP) were compared in human volunteers. After topical application, budesonide was 2-3 times more potent than BDP in inducing "vasoconstriction". After oral administration, on the other hand, budesonide was 2-4 times less potent than BDP in depressing plasma cortisol and changing the total or differential WBC. After inhalation, too, significant differences in favour of budesonide were noted, but the divergence between the drugs was less pronounced. The improved relationship between the topical and systemic glucocorticoid effects of budesonide makes it a promising alternative for aerosol treatment in asthma.

Administration, Oral↗
PubMed1982

Reversal of decreased hepatic lipase and lipoprotein lipase activities after treatment of hypothyroidism.

Plasma lipoprotein concentrations, activities of hepatic lipase and lipoprotein lipase in post-heparin plasma, and the removal rate of exogenous triglyceride were measured in fourteen patients with severe primary hypothyroidism before and after 4 months substitution therapy with 1-thyroxine. Before treatment plasma LDL cholesterol concentrations were markedly increased while HDL cholesterol and plasma triglycerides were in the upper reference range. Thyroxine substitution led to a normalization of LDL cholesterol in all patients. Plasma triglycerides and HDL cholesterol decreased moderately. Hepatic lipase and lipoprotein lipase activities were initially reduced but increased significantly after treatment, by about 170% and 55%, respectively. The increase in hepatic lipase activities was significantly correlated to the increase in serum triiodothyronine levels and also to the reduction in LDL cholesterol concentrations. The decrease in LDL cholesterol was also significantly correlated to the increase in serum triiodothyronine concentration. In two patients initially treated with triiodothyronine, the activity of hepatic lipase, but not that of lipoprotein lipase, increased after 24 and 48 h, while LDL cholesterol levels decreased substantially. We suggest that the reduced activities of hepatic lipase as well as of lipoprotein lipase are important pathogenetic factors for the dyslipoproteinaemia occurring in hypothyroidism and that the low serum triiodothyronine concentration is of major importance for the alterations in lipid transport.

Adolescent↗
PubMed1982

Factors influencing the release of cyclic AMP from mouse thyroid tissue stimulated by TSH in vitro.

The accumulation of cyclic AMP (cAMP) in mouse thyroid tissue in response to TSH in the presence of 1 mM theophylline was accompanied by a release of the nucleotide from the tissue into the incubation medium. This cAMP release was almost rectilinearly related to the time of exposure to TSH, and rectilinearly related to the log concentration of TSH in the range 0.1-5 mU/ml. The cAMP release proved to be independent of the pre-incubation time up to 4 h, and took place also in the absence of methylxanthines when the cAMP level was low. The total cAMP accumulation in response to TSH was augmented by different inhibitors of protein synthesis but the fraction of the nucleotide that was retained intracellularly was increased only by puromycin. Dipyridamole had an effect similar to that of puromycin. Depolarization or treatment with ouabain did not change the distribution of cAMP between tissue and medium. It is concluded that the release of cAMP from thyroid tissue stimulated by TSH may take place under physiological conditions, that it seems to be regulated by the actual concentration of TSH, and that it may be of significance for the regulation of the intracellular cAMP level.

Animals↗
PubMed1982

Topical and systemic glucocorticoid potencies of budesonide, beclomethasone dipropionate and prednisolone in man.

Topical anti-inflammatory ('intracutaneous vasoconstriction') and systemic glucocorticoid potencies (depression of plasma cortisol) were compared in human volunteers after administration of the glucocorticoids budesonide, beclomethasone dipropionate (BDP) and prednisolone. After topical application budesonide was about twice as potent as BDP and more than 1 000 times more potent than prednisolone and hydrocortisone in inducing 'vasoconstriction'. After oral administration, on the other hand, budesonide was one half to one third as potent as BDP in depressing plasma cortisol. After inhalation budesonide was only half as potent as BDP. When inhaled budesonide was compared to oral prednisolone budesonide 1 600 micrograms and prednisolone 5 mg were shown to have the same effect on plasma cortisol. The improved ratio between the topical and the systemic glucocorticoid effect of budesonide, makes the drug a promising alternative for aerosol treatment in asthma.

Adult↗
PubMed1982

Radioimmunoassay and chemical ionization/mass spectrometry compared for plasma cortisol determination.

We describe a method for determination of cortisol in plasma and urine, based on chemical ionization/mass spectrometry with deuterium-labeled cortisol as the internal standard. The within-run precision (CV) was 2.5-5.7%, the between-run precision 4.6%. Results by this method were compared with those by a radioimmunological method (RIANEN Cortisol, New England Nuclear) for 395 plasma samples. The latter method gave significantly higher (approx. 25%) cortisol values.

Administration, Topical↗
PubMed1981

HLA antigens in two siblings with autoimmune Addison's disease.

The diagnosis of autoimmune Addison's disease was established in two siblings by demonstration of serum antibodies against adrenal cortex antigen, elevated P-ACTH combined with a low P-cortisol, and the absence of P-cortisol response to exogenous ACTH. HLA typing in the two siblings and their parents revealed the same HLA phenotype in the two patients. This is compatible with an autosomal recessive mode of inheritance and indicates that a supposed trait for autoimmune Addison's disease may segregate with the HLA complex in the familial form of autoimmune Addison's disease.

Addison Disease↗
PubMed1981

Effect of inhibition of protein synthesis on thyroid cyclic AMP accumulation in vitro.

When thyroid cells in vitro are stimulated by TSH for 2 h cyclic AMP (cAMP) is synthesized at a high rate during the first 25 min of stimulation, thereafter at a lower rate. The mechanism for this reduction of adenyl cyclase activity was studied in vitro using mouse thyroid tissue. As some of the cAMP formed is released from the cells the sum of cAMP in tissue and incubation medium was studied and considered to reflect the accumulated cAMP synthesis as breakdown synthesis as breakdown by phosphodiesterase was minimized by 1 mM theophylline. The TSH stimulated tissue did not release any adenyl cyclase inhibiting factor into the incubation medium. Cycloheximide, 5 micrograms/ml, enhanced the cAMP response to a single or repeated stimulation by TSH. Its effect was visible after 25 min of incubation and remained at about the same size for 2 h, but the levelling off of cAMP synthesis was not prevented but took place at a higher level. The effect of puromycin, 500 microgram/ml, was similar to that of cycloheximide. Also actinomycin D, 1 microgram/ml, enhanced the cAMP response to TSH. It is concluded that a protein synthesis dependent inhibitor of adenyl cyclase is activated by TSH, but it accounts only for a minor part of the adenyl cyclase inhibition that takes place in the later part of a TSH stimulation of the thyroid. Additional adenyl cyclase inhibiting mechanisms must be considered.

Animals↗
PubMed1980

VIP occurs in intrathyroidal nerves and stimulates thyroid hormone secretion.

Vasoactive intestinal polypeptide (VIP) is known to have powerful effects on the secretion from several endocrine and exocrine glands, and occurs in nerves with a ubiquitous distribution in the body. This infers that neuronal VIP may be a regulator of such secretion, and there is evidence that it is involved in the regulation of exocrine pancreatic function. Previous studies have shown that adrenergic and cholinergic nerves participate in the regulation of thyroid hormone secretion. We describe here combined immunohistochemical and immunochemical studies which show that the thyroid of several species is supplied with VIP-containing nerve fibres that surround blood vessels and run between and along thyroid follicles and that in the mouse neuronal VIP participates in the regulation of thyroid hormone secretion through a mechanism that is mediated by cyclic AMP.

Animals↗
PubMed1978

Somatostatin inhibits thyroid hormone secretion induced by exogenous TSH in man.

The effect of somatostatin on thyroid hormone secretion stimulated by TSH in man was studied. The injection of TSH into a thyroid artery during surgery was followed by an increase in the serum concentration of iodothyronines in the corresponding thyroid vein. This increase was significantly lower (p less than 0.02) when somatostatin was given as a bolus injection into a peripheral vein 5 min prior to the administration of TSH, and followed by a continuous infusion for 60 min. Since somatostatin-like immunoreactivity has been localized to some cells of the thyroid gland being in a parafollicular location, it is suggested that somatostatin may be an intrathyroidal regulator of thyroid activity in man.

Adult↗
PubMed1978

Release of cyclic AMP from thyroid cells in vitro.

Half lobes of mouse thyroid gland were incubated in vitro with TSH. They released cyclic AMP (cAMP) into the medium in amounts depending on the concentration of TSH. The release of cAMP was greatest during the first hour of incubation then it occurred at a lower rate. With an incubation time of 45 min the medium cAMP levels ranged from 43.0 +/- 11.9 pmole per mg tissue protein for controls to 296.5 +/- 29.2 pmole per mg tissue protein with 5 mU of TSH in the medium. The tissue cAMP level reached a maximum after 15--30 min of incubation with TSH, then it gradually decreased towards control level during 4 h of incubation. With 25 min of incubation the tissue cAMP level was 28.5 +/- 8.8 pmole per mg tissue protein for controls compared to 194.3 +/- 27.0 pmole per mg tissue protein with 5 mU TSH in the incubation medium. The release of thyroxine was of the same order during the later part of the 4 h incubation period compared to the first one. The results illustrate the quantitative importance of cAMP release, and the fact that in the later part of the incubaion period the cell content of cAMP was low while the release of thyroxine remained high.

Animals↗
PubMed1977

Screening for medullary carcinoma of the thyroid in families with Sipple's syndrome: evaluation of new stimulation tests.

In search of new practical diagnostic methods for the early diagnosis of hereditary medullary carcinoma of the thyroid (MCT) calcitonin release has been studied following induction by pentagastrin, cholecystokinin-pancreozymin (the C-terminal octapeptide, C8-CCK, and the native swine extract), and ethanol in eighteen cases of MCT (all but one clinically occult), three 'borderline cases', seven first degree relatives of patients with hereditary MCT and thirty-five healthy controls. Pentagastrin, subcutaneous (s.c.) or intravenous (i.v.), induced a pronounced and rapid increase of serum calcitonin within 2-5 min. The elevation was roughly proportional to the tumour mass as estimated at operation. Seventeen out of eighteen MCT patients responded to s.c. pentagastrin with a significant increase in serum calcitonin and the response correlated well with that induced by calcium infusion test. Only two blood samples, at times 0 and 5 min, were necessary for diagnosis. In the MCT patients, i.v. pentagastrin produced more pronounced elevations of serum calcitonin than did s.c. pentagastrin, whereas no increase was seen in the control group. The subjective discomfort caused by i.v. pentagastrin was somewhat more intense but lasted shorter than that induced by s.c. administration. No serious complications were seen. All of nine MCT patients responded to C8-CCK with increments in serum calcitonin exceeding those of the control group and both of two responded similarly to the native cholecystokinin-pancreozymin extract. Generally the serum calcitonin response was lower and more variable after C8-CCK than after s.c. or i.v. pentagastrin, and the subjective discomfort was also more pronounced with abdominal cramps during the injection. Ethanol in the dose used was the least effective stimulator for serum calcitonin release. Clinically suspected MCT carriers with palpable tumours can be diagnosed by determination of the basal, i.e. non-stimulated serum calcitonin levels. Other possible Sipple genome carriers, who are at the time clinically healthy with normal basal serum calcitonin, should be subjected to a s.c. or i.v. pentagastrin stimulation test at each examination. These tests are much simpler to perform than a calcium infusion, test, but seem to have about the same sensitivity.

Adolescent↗