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Biomedical subjects

P Hedner

Publications and source records attributed to P Hedner.

At least 37 records · Page 2Linked to original sources
PubMed1987

Erythrocyte thermogenesis in hyperthyroid patients: microcalorimetric investigation of sodium/potassium pump and cell metabolism.

Erythrocyte thermogenesis was studied by microcalorimetry in 11 patients before and after treatment for hyperthyroidism. Cell heat production rate and intracellular Na+ and K+ levels were measured in plasma suspensions of erythrocytes with and without specific inhibition of Na/K ATPase by ouabain. The ouabain induced change in the heat production rate (the Na/K pump thermal power); the erythrocyte intracellular Na+ content and the ouabain sensitive Na+ transport were used to estimate the Na/K pump function. The mean value for heat production rate was 131 +/- 4 mW/L erythrocytes before treatment, which is significantly higher than in euthyroid subjects. A significant decrease (P less than 0.01) to normal levels was recorded following therapy. This decrease, as determined in samples with ouabain, correlated to changes in serum levels of triiodothyronine, T3, (r = .74, P less than 0.01). The Na/K pump thermal power was 11 +/- 2 mW/L erythrocytes (8 +/- 2% of total heat production rate) before and 9 +/- 2 mW/L erythrocytes (8 +/- 2%) after treatment. These two values were not different from those obtained in euthyroid subjects. The erythrocyte Na+ content decreased from 9.9 +/- 2.1 to 4.9 +/- 0.5 mmol/L erythrocytes (P less than 0.001) following normalization of thyroid function. The decrease in intracellular Na+ concentration correlated to the decrease in serum T3 levels, but only when calculated from the data obtained in samples with ouabain (r = .60, P less than 0.05). The relative increase in intracellular Na+ concentrations following addition of ouabain was significantly lower (P less than 0.05) before than after treatment for hyperthyroidism, 37 +/- 10% and 61 +/- 5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Increase in hepatic lipase activity after testosterone substitution in men with hypogonadism of pituitary origin.

Ten men with hypogonadism of pituitary origin were studied before and during testosterone substitution therapy with regard to effects on the activities of hepatic lipase (HL) and lipoprotein lipase (LPL) in postheparin plasma, and on plasma lipoprotein concentrations. The mean (+/- SEM) testosterone level increased from 1.8 +/- 0.5 to 16.3 +/- 2.4 nmol/l. The mean activity of HL rose from 327.1 +/- 35.2 to 432.8 +/- 57.2 mU/ml (p less than 0.02), while the activity of LPL did not change significantly, 71.0 +/- 9.1 mU/ml before and 62.2 +/- 3.8 mU/ml after treatment. No significant alterations in lipoprotein concentrations were recorded. These results indicate that a normal testosterone level is of importance for maintaining the activity of HL in men, thereby contributing to the sex difference previously recorded for HL activity.

Adult↗
PubMed1987

Nasal administration of desmopressin by spray and drops.

A solution of desmopressin was administered intranasally as a spray using a metered dose pump, or as drops using a single dose pipette or rhinyle catheter. Volunteers, and patients with diabetes insipidus, were given an intranasal dose of 20 micrograms desmopressin by each method. The antidiuretic activity was measured by determination of urine osmolality and diuresis. Each delivery system was equally effective in producing a rapid onset of activity, a highly reproducible magnitude of effect and duration of the antidiuretic effect which lasted for more than 8 h. The pipette and spray pump offer a choice of single dose administration without preservative, or for chronic use, well-controlled, reproducible dosing, respectively.

Administration, Intranasal↗
PubMed1987

Increased plasma gonadotropin levels in spontaneous hyperthyroidism reproduced by thyroxine but not by triiodothyronine administration to normal subjects.

In nine hyperthyroid women studied in the follicular phase of the menstrual cycle basal plasma LH concentrations and LH and FSH responses to GnRH were increased compared to those in nine normal women. The increased gonadotropin levels could not be related to changes in body weight or plasma estradiol or serum sex hormone-binding globulin levels, and they approached normal levels during or after treatment of hyperthyroidism. When normal women were treated with T4 (0.5 mg daily for 6-10 days), their mean serum free T4 level increased to about 60% of that in the hyperthyroid patients, while their serum T3 levels increased to a lesser degree. During T4 administration these women had gonadotropin changes similar to those of the hyperthyroid patients. When the normal women took T3 (60-120 micrograms for 6-8 days), their serum T3 level rose almost to the level in the hyperthyroid patients, but basal and GnRH-stimulated LH and FSH remained close to control levels. Dopaminergic blockade with metoclopramide did not alter the gonadotropin response to GnRH in any subject group. We conclude that serum T4 is of greater importance than serum T3 for at least short term gonadotropin regulation.

Adult↗
PubMed1987

Erythrocyte metabolism in hyperthyroidism: a microcalorimetric study on changes in the Embden-Meyerhof and the hexose monophosphate pathways.

Erythrocyte metabolism was studied in vitro by microcalorimetry in 10 hyperthyroid subjects before and after treatment. By inhibiting the enzyme enolase in the Embden-Meyerhof pathway with sodium fluoride (NaF) we have recorded the anaerobic and aerobic contributions in erythrocyte thermogenesis. The decrease in heat production rate in samples with NaF corresponds to the anaerobic contribution, whereas the values from samples with NaF reflect aerobic processes. Before treatment, total heat production rate was 120 +/- 2 mW/l erythrocytes which was higher than the post-treatment value of 99 +/- 2 (P less than 0.001) as well as the value for 14 euthyroid subjects, 108 +/- 2 mW/l (P less than 0.001). The NaF inhibitable rate was 73 +/- 2 before and 63 +/- 1 mW/l after therapy (P less than 0.01). These values correspond to 61 +/- 1 and 64 +/- 1% (n.s.) of the total heat production rate, and were similar to that of 61 +/- 2% for the controls. Heat production rates in the presence of NaF were 47 +/- 1 before and 36 +/- 1 mW/l after therapy (P less than 0.001), representing 39 +/- 1 and 36 +/- 1% of total values, respectively. The present results show that overall metabolism is increased in erythrocytes from hyperthyroid subjects before treatment and returns to normal after normalization of the thyroid function. Moreover, by using microcalorimetry we found that the metabolic activity along the Embden-Meyerhof anaerobic pathway as well as along the hexose monophosphate aerobic pathway in erythrocytes is stimulated by thyroid hormones.

Adult↗
PubMed1986

Thyroid hormone metabolism in thyroid disease as reflected by the ratio of serum triiodothyronine to thyroxine.

In 77 euthyroid subjects the mean ratio between serum triiodothyronine (S-T3) in nmol/l X 10(3) and serum thyroxine (S-T4) in nmol/l was 22.4 with a standard deviation of 4.3. The distribution of the ratio was close to Gaussian. It was not changed in subjects under estrogen effect. The ratio was increased in hypothyroid subjects suggesting a mechanism preserving S-T3 better than S-T4 in thyroid failure. This mechanism seemed independent of TSH as the increasing S-T3/S-T4 ratio in primary hypothyroidism was not correlated to serum TSH (S-TSH), and patients with hypothyroidism of pituitary origin, without any increase in S-TSH, had a significantly elevated S-T3/S-T4 ratio. In subjects taking thyroxine, S-T4 but not S-T3 increased with the dose of thyroxine, leading to decreasing S-T3/S-T4 ratios. This indicates a mechanism that keeps S-T3 within normal limits also when the S-T4 supply is high. This applied also to athyreotic subjects on thyroxine and to subjects on thyroxine plus carbimazole, suggesting that the mechanism is independent of thyroid tissue, uninfluenced by carbimazole, and probably operates via the peripheral metabolism of T4. Changes in the S-T3/S-T4 ratio can be achieved by several mechanisms, and the specificity of ratio changes is low. However, by investigating the ratio S-T3/S-T4 in selected clinical states we can depict the ability of the organism to protect its normal S-T3 level in situations with divergent S-T4 concentrations, even if details about the mechanisms cannot be explained.

Adolescent↗
PubMed1986

Effects of six cholecystokinin (CCK) fragments on insulin secretion in the mouse.

In a recent study it was demonstrated that the C-terminal octapeptide of cholecystokinin (CCK-26-33; often abbreviated CCK-8) and CCK-39 (= CCK--6-33) potently and with the same efficacy stimulated basal insulin secretion when injected intravenously to mice. In the present study, the effects of four other CCK fragments, CCK-30-33 (= CCK-4), CCK-1-33 (= CCK-33), CCK-1-21 (= CCK-21) and CCK-10-20, on basal and glucose-induced insulin secretion were studied. It was found that CCK-33 stimulated insulin secretion. At a dose level of 4.25 nmol/kg, plasma insulin concentrations were elevated by 58 +/- 7 microU/ml (P less than 0.001). On the contrary, neither CCK-4, nor CCK-21, nor CCK-10-20 displayed any effect on basal insulin secretion, not even at high dose levels. When injecting CCK-8, CCK-33 or CCK-39 at dose levels substimulatory on basal insulin secretion (0.53 nmol/kg), together with glucose, CCK-39 potentiated glucose-induced insulin secretion whereas CCK-8 and CCK-33 were without effects. In contrast, at the higher dose level of 5.3 nmol/kg, CCK-8, CCK-33, and CCK-39 all potentiated glucose-induced insulin secretion. The three other fragments, CCK-4, CCK-21, and CCK-10-20, were all without effects on glucose-induced insulin secretion. In conclusion, the potent stimulatory action on basal insulin secretion in the mouse exerted by various CCK fragments is confined to the C-terminal octapeptide (= CCK-8 or CCK-26-33).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of norepinephrine on basal and thyrotropin-stimulated thyroid hormone secretion in the mouse.

The possibility that norepinephrine stimulates basal but inhibits TSH-induced thyroid hormone secretion was explored by the use of in vivo and in vitro techniques. Basal thyroid hormone secretion was defined as TSH-independent secretion, experimentally obtained in vivo by pretreatment with T4 or T3. In mice pretreated with 125I and T4, norepinephrine enhanced baseline blood radioiodine levels, but in control mice, norepinephrine failed to alter basal plasma T4 levels. To study whether the stimulated release of radioiodine truly reflects stimulated thyroid hormone secretion, the nature of the radioiodine that was elevated by norepinephrine after 125I pretreatment was investigated. In controls, the fraction of radioiodine that was bound to thyroid hormones was 24.6 +/- 0.8% (+/- SE) of the total radioiodine. This figure increased to 31.9 +/- 1.1% (P less than 0.001) in response to norepinephrine. Further, by a technique of binding the released radioiodine to specific anti-T4 antiserum, norepinephrine was found to increase secretion of radiolabeled T4 by 22 +/- 2% (P less than 0.001). Thus, it is concluded that norepinephrine stimulates basal thyroid hormone secretion in vivo, and that its failure to alter plasma T4 levels is due to the low sensitivity of the technique. In contrast, it was found that norepinephrine inhibits the thyroid stimulatory effect of TSH in vivo. Under in vitro conditions, norepinephrine was found to increase the release of radioiodine that was bound to thyroid hormones from thyroid glands of mice that had been pretreated with 125I. However, norepinephrine failed to alter the baseline thyroid content of cAMP, yet it inhibited the cAMP-accumulating effect of TSH. In conclusion, the present study demonstrates that norepinephrine exerts a dual effect on thyroid hormone secretion in the mouse; it stimulates basal but inhibits TSH-induced thyroid hormone secretion.

Animals↗
PubMed1985

Stimulation of cyclic adenosine 3',5'-monophosphate formation in rabbit choroid plexus by beta-receptor agonists and vasoactive intestinal polypeptide.

The formation of cyclic adenosine 3',5'-monophosphate (cAMP) was determined in blood-free choroid plexus homogenates from all ventricles of rabbit using a competitive protein binding technique. Previous stimulation of the intact plexus tissue in vitro with sympathomimetic drugs or vasoactive intestinal polypeptide (VIP) leads to increased local synthesis of cAMP. Tests with selective beta-receptor agonists and antagonists suggested that beta 1-receptors predominate, which is consistent with studies of sympathomimetic effects on cerebrospinal fluid production in vivo.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Reversal of increased whole blood and plasma viscosity after treatment of hypothyroidism in man.

Blood and plasma viscosity was measured in 13 patients with hypothyroidism before and during replacement therapy with l-thyroxine. Blood viscosity was measured at natural hematocrit and after adjustment to 40%. The values were compared to those of 12 healthy subjects. Both blood viscosity at hematocrit 40% and plasma viscosity were increased in the hypothyroid state and decreased to the levels of the reference group after treatment. The therapy-induced changes in blood and plasma viscosity were intercorrelated at low but not at high shear rates. The changes in viscosity were not correlated to the reductions in lipoprotein concentrations resulting from therapy. The institution of l-thyroxine replacement therapy was also followed by reductions in erythrocyte sedimentation rate and diastolic blood pressure, both with significant correlations to the decrease in blood viscosity. It is concluded that in hypothyroidism there are changes in both plasma and erythrocytes that increase blood viscosity, with normalization upon treatment with l-thyroxine to euthyroidism.

Adult↗
PubMed1985

Influence of thyroid hormones on transport function and Na+-K+-ATPase activity in the rat choroid plexus.

The sympathomimetic stimulation of choroid plexus transport and secretion in rat seems to be mediated by beta-adrenergic receptors. In the present report the effect of induced changes in thyroid function on transport mechanisms in the rat choroid plexus was studied. Following induction of hyperthyroidism (treatment with T3 for 10 days) the tissue/medium ratio (T/M) for choline uptake in choroid plexus in vitro decreased significantly by 68%. The Na+-K+-ATPase activity showed a statistically significant increase of about 16%. Also following cervical sympathectomy, T3 caused a reduction of the T/M for choline, to the same level as in the non-sympathectomized animals, while the effect of T3 on the Na+-K+-ATPase activity was changed into a 22% decrease. Hypothyroidism (administration of PTU in the drinking water) had little or no effect on the uptake and accumulation of choline in the choroid plexus. The Na+-K+-ATPase activity was reduced by 40%, in contrast to the stimulating effect of T3. There is, hence, reason to believe that the transport of choline in the choroid plexus is only partly regulated by adrenergic mechanisms acting via Na+-K+-ATPase. The major effect of T3 on the choline uptake may be exerted by a mechanism different from the ATPase activity and not involving adrenergic receptors.

Animals↗
PubMed1985

Platelet and adipocyte thermogenesis in hypothyroid patients: a microcalorimetric study.

Direct microcalorimetry was used for measurements of heat production in cell suspensions of platelets and adipocytes, obtained from hypothyroid patients before and after 3 months on full L-thyroxine substitution. Platelet heat production was significantly lower than normal before treatment and increased in all 10 patients studied; the mean value increased from 51.3 +/- 1.6 fW/cell before to 57.1 +/- 1.8 fW/cell after therapy (P less than 0.001). Similarily, adipocyte heat production was initially significantly lower than normal and increased during treatment in all 6 patients investigated. The mean value for heat production per adipocyte was 18.8 +/- 1.7 pW/cell before and 32.4 +/- 2.5 pW/cell after therapy (P less than 0.025), which is still below the level recorded in lean healthy subjects. The adipocyte size did not change significantly. The increase in adipocyte heat production was correlated to the increase in S-triiodothyronine levels (r = 0.84, P less than 0.05). In hypothyroidism, the total metabolic activity seems to be comparatively more reduced in adipocytes than in platelets. A difference may exist between these cells with regard to recovery of normal metabolic activity during treatment for hypothyroidism. Direct microcalorimetry appears to be an adequate method for monitoring net metabolic effects of thyroid hormones in these cells.

Adipose Tissue↗
PubMed1985

Glucose tolerance and insulin and C-peptide responses after various insulin secretory stimuli in hyper- and hypothyroid subjects before and after treatment.

Immunoreactive insulin (IRI) and C-peptide secretory responses to terbutaline, glucagon, glucose and a standardized meal during continuous blood glucose monitoring were investigated in hyper- and hypothyroid patients before and after treatment. The beta 2-adrenoceptor agonist terbutaline (125 micrograms IV) induced prompt IRI and C-peptide responses in hyperthyroid patients. On the contrary, in the hypothyroid, no insulin or C-peptide responses were seen despite a slight enhancement of blood glucose concentrations. Thyroxine treatment of these patients improved the IRI and C-peptide responses and no blood glucose increment was then seen. Glucagon (250 micrograms IV) induced prominent IRI and C-peptide responses of similar magnitude in hyper- and hypothyroid patients before as well as after treatment. Before treatment, the blood glucose increment was greater in the hypothyroid patients than in the hyperthyroid but after treatment no difference between the 2 groups was seen. After a small load of glucose (6 g IV) no apparent difference in glucose tolerance was seen between hyper- and hypothyroid patients. However, the hyperthyroid patients had greater IRI and C-peptide responses to glucose than the hypothyroid but the differences diminished after treatment. Before treatment, hypothyroid patients had lower blood glucose response to a meal intake than hyperthyroid patients but no differences were seen between the 2 patient groups with regard to IRI- and C-peptide responses. After treatment, no differences between the 2 groups were seen with regard to blood glucose, IRI or C-peptide responses to the meal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Recovery of the hypothalamus-pituitary-adrenal axis after short term high dose corticosteroid treatment in neurosurgical practice.

The recovery of the hypothalamus-pituitary-adrenal axis after high-dose short-term steroid treatment was investigated in 18 patients undergoing stereotactic thalamotomy during local anaesthesia, in whom perioperative betamethasone was given in a high dose for 4-5 days and withdrawn without tapering. There were no untoward clinical effects of the abrupt withdrawal of the steroid. Seven patients undergoing the same operation without steroid treatment served as controls. The recovery of the hypothalamus-pituitary-adrenal axis after steroid treatment was studied by basal plasma cortisol levels. In 12 patients the reserve capacity of the system was investigated by the cortisol response to insulin induced hypoglycemia as well. It was found that the basal plasma cortisol levels had normalized 2 days after the abrupt withdrawal of betamethasone. In spite of normalized basal cortisol levels the capacity to respond to stress was reduced for a further 3 days. Six to seven days after the steroid withdrawal the stress response was, however, completely restored. It is concluded that high dose, short term steroid treatment can be withdrawn abruptly, omitting the usual tapering of the dose. During the first week after steroid withdrawal the cortisol response to stress is reduced even in the presence of normal basal cortisol levels. During this period extra corticosteroids must be supplied in case of an emergency situation or an operation.

Adult↗
PubMed1984

Treatment of hyperthyroidism: effects on hepatic lipase, lipoprotein lipase, LCAT and plasma lipoproteins.

The activities of hepatic lipase and of lipoprotein lipase, the elimination rate of exogenous triglyceride and the cholesterol esterification rate were determined and related to plasma lipoprotein concentrations in 16 patients before and after treatment for hyperthyroidism. The activity of hepatic lipase was significantly higher (65%) before than after treatment, while the activity of lipoprotein lipase and the elimination rate of exogenous triglyceride remained unchanged. The endogenous cholesterol esterifying ability decreased after treatment, whereas no change occurred in the fractional cholesterol esterification rate measured with normal plasma as substrate. The concentrations of LDL-cholesterol and HDL-cholesterol increased significantly after treatment. The decrease in hepatic lipase activities was correlated to the decrease in S-T3 concentrations (r = 0.77, P less than 0.001) and to the increase in HDL-cholesterol concentrations (r = 0.51, P less than 0.05). The activities of lipoprotein lipase were positively correlated to the concentrations of HDL-cholesterol both before (r = 0.54, P less than 0.05) and after (r = 0.59, P less than 0.05) treatment. These results support the view that hepatic lipase and lipoprotein lipase are both important determinants of plasma HDL concentrations and suggest that an increased hepatic lipase activity contributes to the lower HDL levels in hyperthyroid patients.

Adolescent↗
PubMed1984

Normal reference interval for thyrotropin response to thyroliberin: dependence on age, sex, free thyroxin index, and basal concentrations of thyrotropin.

We measured the thyrotropin response (delta TSH) to 200 micrograms of thyroliberin in 131 subjects without thyroid dysfunction or other disease and with basal values for thyroid function that were within the normal reference intervals for our laboratory. By univariate and multivariate statistical methods we found delta TSH to be significantly influenced by the basal concentration of thyrotropin (TSH0) and the free thyroxin index (FT4I). When the effects of variations in TSH0 and FT4I were eliminated, delta TSH in men under 40 years of age did not differ from that in women. A decrease in delta TSH with increasing age was found in men but not in women. Thus a reference interval for delta TSH should consider TSH0, FT4I, and, in men, age. On the basis of multiple linear regression analysis, we constructed a formula for delta TSH reference intervals that takes into account individual values for TSH0 and FT4I. The formula should be applicable for women, regardless of age, up to 77 years and for men under 40 years. For older men a correction for the age-related decrease in delta TSH must be applied.

Adult↗
PubMed1983

Interaction of gastric inhibitory polypeptide (GIP) and cholecystokinin (CCK-8) with basal and stimulated insulin secretion in mice.

The interaction of GIP and CCK-8 with basal insulin secretion and with insulin release induced by glucose or by the beta-adrenoceptor agonist L-isopropylnoradrenaline (L-IPNA) was studied in mice. GIP and CCK-8, when injected in threshold doses not affecting basal insulin secretion, did markedly enhance basal insulin release when given simultaneously. Maximal doses of the two peptides, on the other hand, did not potentiate each other's action, but displayed a pure additive effect on insulin secretion. Insulin release induced by a half-maximal dose of glucose was slightly potentiated by the threshold dose of GIP and markedly potentiated by the maximal dose i.e. the effect was greater than the algebraic sum of the individual actions. CCK-8 was without potentiating effect at both dose levels. The combination of GIP and CCK-8 did not display the potentiating effect of GIP alone on glucose-stimulated insulin release. However, an additive action was observed at both dose levels. Insulin release stimulated by a half-maximal dose of L-IPNA was not affected by either GIP or CCK-8 at the threshold doses. The combination of the two peptides and L-IPNA, however, displayed a lower response than that expected from an additive effect. Similarly, at the high dose level of the peptides, the combination of GIP plus CCK-8 and L-IPNA as well as CCK-8 alone plus L-IPNA displayed a lower insulin response than that expected from an additive effect. GIP alone plus L-IPNA gave the expected additive effect. The results show that interactions between different gastrointestinal polypeptides with insulin release may greatly change the expected effect exerted by any individually tested peptide, and that the action of the peptides on stimulated insulin secretion is highly dependent on the nature of the secretagogue. Such complex interactions must be borne in mind in the search for the incretin factor(s).

Adrenergic beta-Agonists↗