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Biomedical subjects

R Rupprecht

Publications and source records attributed to R Rupprecht.

137 records · Page 8Linked to original sources
PubMedDate not supplied

Glucocorticoids modulate soluble interleukin-2 receptor levels in vivo depending on the state of immune activation and the duration of glucocorticoid exposure.

We have studied the modulation of circulating soluble interleukin-2 receptor (sIL-2R) levels by glucocorticoids in subjects with different states of immune activation. In contrast to normal subjects, 40 mg methylprednisolone administration over 6 days resulted in a significant fall of elevated circulating sIL-2R levels (p < 0.05) in patients with active atopic dermatitis, most pronounced in those patients showing the highest pre-treatment levels of sIL-2R and scores of disease activity. Following administration of 1 mg dexamethasone, sIL-2R levels remained unchanged both in normal subjects and patients with atopic dermatitis. Circulating sIL-2R levels were significantly decreased in patients with long-term hypercortisolism due to Cushing's disease (p < 0.05) and significantly elevated (p < 0.05) in hypocortisolemic patients. Blockade of adrenal cortisol secretion by 1.5 g metyrapone did not change sIL-2R levels in normal subjects and sIL-2R levels were not affected in depressive patients, either before or after clinical remission or following 1.5 g metyrapone administration. These data suggest that the effect of glucocorticoid administration on circulating sIL-2R levels depends on the state of immune activation and the duration of glucocorticoid exposure. The circulating sIL-2R levels show significant changes in patients with chronic alterations of endogenous glucocorticoid secretion and in response to prolonged glucocorticoid therapy in disorders with immune activation.

Addison Disease↗
PubMedDate not supplied

Effects of glucocorticoids on the regulation of the hypothalamic-pituitary-somatotropic system in depression.

In order to evaluate the possible effect of glucocorticoids as neuromodulators of the hypothalamic-pituitary-somatotropic system in depression, cortisol, growth hormone (GH), and insulin-like growth factor I (IGF-I) concentrations were studied before and after oral administration of 1 mg dexamethasone at 11 p.m. in 16 patients during depression and after recovery and in 28 healthy controls. While there were no significant differences in GH and IGF-I levels between depressed, recovered and control subjects, GH and IGF-I concentrations of cortisol non-suppressors were significantly elevated compared to suppressors. Moreover, post-dexamethasone cortisol, GH, and IGF-I levels were positively correlated. Dexamethasone had a stimulating effect on GH and IGF-I values in patients during depression and in cortisol non-suppressors only; this effect was absent in recovered and in control subjects and in cortisol suppressors. Thus, hypercortisolemia may be of great importance for the dysregulation of the hypothalamic-pituitary-somatotropic system reported in depression.

Adult↗
PubMedDate not supplied

Lymphocyte glucocorticoid receptor binding during depression and after clinical recovery.

Lymphocyte glucocorticoid receptor binding parameters were studied in 15 severely depressed patients during depression and after clinical recovery, and in 15 healthy controls. There was no difference in glucocorticoid receptor number or affinity between depressed patients and recovered or control subjects. Afternoon ACTH and cortisol concentrations did not differ significantly between the three groups. No relationship could be established between glucocorticoid receptor binding and antidepressant medication. These data support the view of an impaired ligand-induced plasticity of glucocorticoid receptor regulation rather than the hypothesis of decreased glucocorticoid receptor numbers during depression.

Adolescent↗
PubMedDate not supplied

Fluoxetine decreases concentrations of 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone (THDOC) in major depression.

There is evidence for a differential alteration in the concentrations of 3 alpha-reduced neuroactive steroids in major depression. Because it has been suggested that fluoxetine may shift the activity of the 3 alpha-hydroxysteroid oxidoreductase towards the reductive direction, treatment of major depression may be accompanied by a further increase in plasma 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone (THDOC) concentration. We studied eight male depressed patients before and after treatment with fluoxetine and compared them to healthy age-matched control subjects. Blood samples were quantified for 3 alpha, 5 alpha-tetrahydroprogesterone, 3 alpha,5 beta-tetrahydroprogesterone (THP) and THDOC by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. Compared to control subjects, concentrations of THDOC were higher in depressed patients and decreased after fluoxetine treatment. In contrast, THP concentrations were lower in depressed patients and increased after fluoxetine treatment. Our results give further evidence for a disequilibrium of 3 alpha-reduced neuroactive steroids in major depression, which is normalized by treatment with fluoxetine.

Adult↗
PubMedDate not supplied

Repetitive transcranial magnetic stimulation induces active coping strategies and attenuates the neuroendocrine stress response in rats.

The effects of repetitive transcranial magnetic stimulation (rTMS) on various brain functions were investigated in adult male Wistar rats. The stimulation parameters were adjusted according to the results of accurate computer-assisted, magnetic resonance imaging-based reconstructions of the current density distributions induced by rTMS in the rat and human brain, ensuring comparable stimulation patterns in both cases. The animals were subjected to daily rTMS-treatment (three trains of 20 Hz; 2.5 s) for 8 weeks from the age of 4 weeks on. In the forced swim test these rats showed a more active stress coping strategy than the control rats. This was accompanied by a significantly attenuated stress-induced elevation of plasma ACTH concentrations. Pituitary changes accounting for the attenuation were ruled out by the corticotropin-releasing hormone test. Baseline concentrations of ACTH and corticosterone were indistinguishable in the two groups. No changes were found in the anxiety-related behavior of the rats on the elevated plus-maze or in behavior during the social interaction test. Accordingly, the binding characteristics of the benzodiazepine agonist [(3)H]flunitrazepam at the benzodiazepine/gamma-aminobutyric acid type A receptor complex were similar in the rTMS and control groups. In summary, chronic rTMS treatment of frontal brain regions in rats resulted in a change in coping strategy that was accompanied by an attenuated neuroendocrine response to stress, thus revealing parallels to the effects of antidepressant drug treatment.

Adaptation, Psychological↗
PubMedDate not supplied

Sleep deprivation and hypothalamic-pituitary-adrenal (HPA) axis activity in depressed patients.

In the present study we investigated HPA axis activity in depressed patients treated with partial sleep deprivation (PSD) in order to identify endocrinological characteristics related to PSD responsiveness. Thirty-three drug-free patients (14 men, 19 women) suffering from major depression according to DSM-IV criteria were treated with PSD. Response to PSD was defined as a reduction of at least 30% according to the 6-item version of the Hamilton Depression Scale (6-HAMD). Subsequently, the combined dexamethasone-suppression/CRH-stimulation test (DEX/CRH test) was performed. Patients were pretreated with 1.5 mg dexamethasone (DEX) at 23:00 h and challenged with 100 microg corticotropin-releasing hormone (CRH) the following day. Postdexamethasone cortisol concentrations (before CRH administration) served as parameters for the DST status (dexamethasone suppression test). The cortisol stimulation after CRH was used as measurement for the DEX/CRH test status. Of the depressive patients, 54.5% (18 out of 33) responded to PSD. DST suppressors (postdexamethasone cortisol levels < 15 ng/ml) showed a significantly greater reduction in 6-HAMD scores after PSD than DST nonsuppressors. Furthermore, a significant negative correlation between postdexamethasone cortisol levels and reduction in 6-HAMD scores after PSD could be established. However, there was no relationship between the cortisol stimulation following CRH challenge and response to PSD. Although the combined DEX/CRH challenge test is a more sensitive marker for HPA axis dysregulation in depression than the standard DST, the negative feedback of the HPA system reflected by the DST status is apparently more closely associated with response to partial sleep deprivation in major depressive disorder.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

The neuropsychopharmacological potential of neuroactive steroids.

In addition to the well-known genomic effects of steroid molecules via intracellular steroid receptors, certain steroids rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. Several of these steroids accumulate in the brain after local synthesis or after metabolism of adrenal steroids. The 3 alpha-hydroxy ring A-reduced pregnane steroids allopregnanolone and tetrahydrodeoxycorticosterone have been thought not to interact with intracellular receptors but enhance 7-aminobutyric acid (GABA)-mediated chloride currents, whereas pregnenolone sulfate and dehydroepiandrosterone (DHEA) sulfate display functional antagonistic properties at GABAA receptors. We demonstrated that these neuroactive steroids can regulate also gene expression via the progesterone receptor after intracellular oxidation. Thus, in physiological concentrations these neuroactive steroids regulate neuronal function through their concurrent influence on transmitter-gated ion channels and gene expression. When administered in animal studies, memory enhancing effects have been shown for pregnenolone sulfate and DHEA. The 3 alpha-hydroxy ring A-reduced neuroactive steroids predominantly display anxiolytic, anticonvulsant and hypnotic activities. Sleep studies evaluating the effects of progesterone as a precursor molecule for these neuroactive steroids revealed a sleep EEG pattern similar to that obtained by the administration of benzodiazepines. These findings extend the concept of "cross-talk" between membrane and nuclear hormone effects and provide a new role for the therapeutic application of these steroids in neurology and psychiatry.

Animals↗
PubMedDate not supplied

Neuropsychopharmacological properties of neuroactive steroids.

In addition to the well-known genomic effects of steroid molecules via intracellular steroid receptors, certain steroids rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. Several of these steroids accumulate in the brain after local synthesis or after metabolism of adrenal steroids. The 3alpha-hydroxy ring A-reduced pregnane steroids allopregnanolone and tetrahydrodeoxycorticosterone have been thought not to interact with intracellular receptors, but enhance gamma-aminobutyric acid (GABA)-mediated chloride currents, whereas pregnenolone sulfate and dehydroepiandrosterone (DHEA) sulfate display functional antagonistic properties at GABA(A) receptors. We demonstrated that these neuroactive steroids can regulate also gene expression via the progesterone receptor after intracellular oxidation. Thus, in physiological concentrations these neuroactive steroids regulate neuronal function through their concurrent influence on transmitter-gated ion channels and gene expression. When administered in animal studies, memory-enhancing effects have been shown for pregnenolone sulfate and DHEA. The 3alpha-hydroxy ring A-reduced neuroactive steroids predominantly display anxiolytic, anticonvulsant, and hypnotic activities. Sleep studies evaluating the effects of progesterone as a precursor molecule for these neuroactive steroids revealed a sleep electroencephalogram pattern similar to that obtained by the administration of benzodiazepines. These findings extend the concept of a "cross-talk" between membrane and nuclear hormone effects and provide a new role for the therapeutic application of these steroids in neurology and psychiatry.

Dehydroepiandrosterone↗
PubMedDate not supplied

In vivo and in vitro effects of glucocorticoids on lymphocyte proliferation in man: relationship to glucocorticoid receptors.

Interrelations between the hypothalamic-pituitary-adrenal system (HPA) and the immune system represent a well-documented biological phenomenon. While in vitro administration of glucocorticoids may inhibit concanavalin A (Con A)- and phytohemagglutinin (PHA)-induced T-cell proliferation, pokeweed mitogen (PWM)-driven B-cell mitogenesis is relatively resistant to glucocorticoids. To further explore the link between the HPA and the immune system in relation to glucocorticoid receptor function, dose-response curves were obtained for Con A- and PHA-induced T-cell mitogenesis, PWM-generated B-cell mitogenesis and spontaneous lymphocyte proliferation in 13 healthy controls. Glucocorticoid effects were assessed in vivo by depletion of endogenous glucocorticoids after oral administration of 1.5 g metyrapone (MET) and subsequent glucocorticoid replacement, and in vitro by incubation of the cells with different doses of dexamethasone (DEX). There was a significant decrease in PWM-induced B-cell mitogenesis and a more pronounced effect of DEX administered in vitro on spontaneous lymphocyte proliferation after MET treatment when compared with the DEX plus MET pretreated condition in vivo. These data suggest that the inhibition of spontaneous lymphocyte proliferation by glucocorticoids in vitro is related to glucocorticoid receptor function. The decrease in PWM-generated B-cell proliferation following cortisol depletion by MET may be seen in connection with impaired glucocorticoid-mediated induction of interleukin-1 receptor synthesis.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Thyroid response to dexamethasone: a study on normal controls and patients with psychogenic sexual dysfunction.

Pre- and postdexamethasone triiodothyronine (T3), thyroxine (T4), and TSH levels of thirteen patients with psychogenic sexual dysfunction and thirteen controls were studied. Patients showed lowered T4 levels in comparison with the control group whereas T3 and TSH levels did not differ significantly. Dexamethasone had a suppressive effect on TSH in patients and in controls while T3 levels were suppressed in the control group only. Patients scored significantly higher on the Hamilton Depression Scale than controls. These results compared with results obtained in patients recovered from major depression might point to endocrinological as well as clinical interrelations between psychogenic sexual dysfunction and minor depression.

Adult↗