Biomedical subjects
Publications and source records attributed to U Voderholzer.
This is a report of one of the few cases of an adult form of metachromatic leukodystrophy with almost exclusively psychiatric symptoms. This should point out the importance of a careful organic diagnostic assessment in all patients with the first manifestation of a psychiatric disease. In this case an investigation of the patient's family confirmed the heterozygote genetic origin of the disease.
We report herein the effects of the beta-adrenergic agonist clenbuterol on desipramine (DMI)-induced growth hormone (GH), prolactin (PRL) and cortisol secretion in healthy male subjects. In the first study, nine subjects were treated with either clenbuterol (0.04 mg, p.o.) or placebo. In the second study, 12 subjects received either DMI (50 mg, i.v.) alone or in combination with clenbuterol (0.04 mg, p.o.) given 60 min prior to DMI administration. Clenbuterol alone had no influence on GH, PRL, or cortisol concentrations, compared to placebo. DMI alone caused GH stimulation (mean maximum = 15.7 +/- 3.4 ng/ml), which was significantly lower after combined administration of DMI and clenbuterol (mean maximum = 7.7 +/- 1.6 ng/ml) (p less than or equal to 0.01). DMI-induced PRL and cortisol stimulation was not influenced by clenbuterol pretreatment. These results indicate the inhibiting influence of noradrenergic beta-receptors on GH stimulation.
Pharmacoendocrinological studies have shown that psychotropic drugs with different actions have different effects on anterior pituitary hormone secretion in man. Substances with different effects on the central nervous system are characterized by a different pharmacoendocrinological profile. Studies with various receptor blockers have shown varying influences on the DMI-induced growth hormone, prolactin, and ACTH/cortisol secretion. Growth hormone stimulation was shown to be mediated by alpha 2-receptors and inhibited by beta-receptors. Investigations in male and female endogenous depressive patients demonstrated a significantly blunted growth hormone response to DMI compared with age- and sex-matched healthy subjects. A comparative study in male endogenous depressive patients showed a significantly diminished growth hormone stimulation both after DMI and after growth hormone-releasing hormone compared to healthy male subjects. In further tests a simultaneous application of four releasing hormones (GHRH, CRH, GnRH, TRH) was used. These investigations showed a significantly lower GH stimulation in endogenous depressive patients compared with age- and sex-matched healthy subjects, but not in neurotic depressive or schizophrenic patients. Cortisol stimulation was similar in all groups of patients and healthy subjects. TSH stimulation was significantly lower in endogenous depressive and schizophrenic patients than in healthy subjects. Somatomedin-C concentrations were significantly elevated in endogenous depressed patients compared with healthy subjects. The blunted growth hormone response in endogenous depression could be explained by inhibitory influences such as increased somatomedin-C concentrations or a hyperactivity of central beta-adrenergic-receptors.
Nine healthy, male subjects received controlled-rate i.v. infusions of a new formulation of pirenzepine to produce constant plasma levels of 40 ng/ml and 105 ng/ml. They also received stepped infusions resulting in plasma levels of 20, 40, 80 and 40 ng/ml for defined periods. Peptone-stimulated gastric acid and volume secretion and near point vision decreased dose dependently, whereas gastric acidity was unchanged. There was a significant correlation between inhibition of gastric acid secretion and the pirenzepine concentration in plasma and in gastric juice. During the stepped i.v. infusion, changes in near point vision were closely related to the plasma drug concentration. Antimuscarinic side-effects occurred more frequently when the plasma drug level was high. Overall, there was a close relationship between the plasma concentrations and the effects and side-effects of pirenzepine. Its gastric inhibitory action was characterized only by a reduction in gastric volume secretion. Increasing plasma concentrations during the first days of treatment may be essential for its efficacy as an antiulcer drug.
Telenzepine is an analogue of pirenzepine with a higher potency and similar selectivity for M1-receptors in animals. In this placebo controlled, double blind, randomised study mean peptone stimulated gastric acid secretion (mean +/- SEM) of 10 male healthy subjects (58 +/- 6 mmol H+/3 h for placebo) was significantly and dose dependently inhibited by oral telenzepine (2 mg: 31 +/- 5, 3 mg: 23 +/- 5, 5 mg: 21 +/- 4 mmol H+/3 h). Telenzepine 3 and 5 mg were significantly stronger than pirenzepine 50 mg orally (37 +/- 8 mmol H+/3 h). Mean percentage acid inhibition was 37% for pirenzepine, and 48, 61, and 64% for 2, 3, and 5 mg telenzepine, respectively. Basal and peptone stimulated gastrin release was unaffected. Mean salivary output per three hours declined moderately from 156 +/- 45 g (placebo) to 136 +/- 45 g with pirenzepine and significantly to 88 +/- 28 g, 95 +/- 39 g and 39 +/- 13 g with telenzepine 2, 3, and 5 mg, respectively. There was a parallel effect on Na+, K+, Ca++ and amylase output in saliva. Near point vision was not altered by either drug. Pulse rates were lowered by both substances. Complaints of dry mouth were more frequent with telenzepine 5 mg. On a molar basis telenzepine proved to be a 25 and 50 times more potent inhibitor of gastric and salivary secretion, respectively.
The fast but short-lasting improvement of depressive symptoms by sleep deprivation (SD) in about 60% of patients with a major depressive disorder is well established, but the mechanisms of action are still not clear. Recent studies suggest that changes in non rapid eye movement (NREM) sleep, especially in slow wave activity (SWA), could be associated with the therapeutic outcome of SD. In the current study, spectral analysis of NREM sleep EEG directly prior to SD was performed to determine if automatically derived sleep parameters predict SD response. Sixteen pair matched and drug free patients with a major depressive disorder, 8 SD responders and 8 non-responders (response criterion: 50% reduction on the 6-item HAMD score), were included. Average EEG spectral power was calculated for the whole night before SD and for single NREM episodes. While whole-night averages of spectral power did not differ significantly between subgroups, SD responders showed a steady decrease of SWA across successive NREM episodes, whereas in non-responders an increase from the first to the second episode was observed. The different distribution of SWA was significantly expressed in the delta sleep ratio (quotient of SWA in the first to the second NREM episode). In conclusion, a high delta sleep ratio is a positive predictor for SD response. Referred to psycho- and pharmacotherapeutic results it is hypothesized that low and high values of the delta sleep ratio characterize subgroups of depressed patients with different neurobiological alterations, which could be relevant for further scientific and therapeutic approaches.
Disturbances of sleep are typical for most depressed patients and belong to the core symptoms of the disorder. Polysomnographic sleep research has demonstrated that besides disturbances of sleep continuity, in depression sleep is characterized by a reduction of slow wave sleep and a disinhibition of REM sleep, with a shortening of REM latency, a prolongation of the first REM period and increased REM density. These findings have stimulated many sleep studies in depressive patients and patients with other psychiatric disorders. In the meantime, several theoretical models, originating from basic research, have been developed to explain sleep abnormalities of depression, like the two-process-model of sleep and sleep regulation, the GRF/CRF imbalance model and the reciprocal interaction model of non-REM and REM sleep regulation. Interestingly, most of the effective antidepressant agents suppress REM sleep. Furthermore, manipulations of the sleep-wake cycle, like sleep deprivation or a phase advance of the sleep period, alleviate depressive symptoms. These data indicate a strong bi-directional relationship between sleep, sleep alterations and depression.