RESUMEN
The increasing migration of people from their homeland in far distant regions to Europe in the last few years has strongly influenced the rise of previously rarely seen diseases. They not only originate from the respective homeland but also from the transit countries during the migration process. We report the case of a 27-year-old male migrant from Eritrea, who after months of flight as a refugee travelling through various African countries, presented at our hospital with a progressive, painful radiculopathy. Whole spine magnetic resonance imaging (MRI) showed a focus located in the myelon, extending from T11 to the medullary conus. The differential diagnostic clarification ultimately revealed an infection with Schistosoma mansoni. After guideline-conform treatment with praziquantel for 3 days and additional administration of corticosteroids for 3 months, a slow regression of the findings and improvement of the symptoms could be shown clinically and by MRI. This case study shows the importance of taking the medical history and that a closer look at the potential exposure in the homeland and transit countries should be of great benefit in reaching the diagnosis, especially in patients with a migration background.
Asunto(s)
Neuroesquistosomiasis , Esquistosomiasis mansoni , Corticoesteroides/uso terapéutico , Adulto , Animales , Antihelmínticos/uso terapéutico , Eritrea , Europa (Continente) , Humanos , Masculino , Neuroesquistosomiasis/diagnóstico por imagen , Neuroesquistosomiasis/tratamiento farmacológico , Praziquantel/uso terapéutico , Refugiados , Schistosoma mansoni , Esquistosomiasis mansoni/diagnóstico por imagen , Esquistosomiasis mansoni/tratamiento farmacológicoRESUMEN
Various peptides including corticotropin-releasing hormone (CRH) exert selective effects on sleep structure and noctural secretions of cortisol and growth hormone (GH). In animal studies analeptic effects and sleep disturbances after thyrotropin-releasing hormone (TRH) administration have been observed; studies of endocrine function in depressed patients suggest a pathological activity of CRH and TRH as compared with that in healthy volunteers. As the role of TRH in the regulation of the sleep endocrine pattern in humans has not yet been clarified, we performed a study to examine the effects of pulsatile administration of TRH on the sleep EEG pattern and the nocturnal secretions of cortisol and GH in 7 healthy male subjects. The sleep EEG was recorded from 23.00 to 07.00 h, and blood samples were collected every 20 min from 20.00 to 07.00 h for the analysis of GH and cortisol concentrations during intravenous administration of placebo or 4 x 50 microgram TRH at 22.00, 23.00, 24. 00, and 01.00 h. In contrast to the well-known effects of CRH on the sleep endocrine pattern, TRH exerts only a weak effect on the sleep EEG which is reflected in a slight decrease in sleep efficiency associated with a trend to wakefulness during the night. Furthermore, after TRH administration, the cortisol rise appeared earlier, and a nonsignificant tendency to an increased secretion of cortisol during the first half of the night was found. The GH secretion did not differ significantly after application of TRH or placebo. The activating, albeit weak, effect of TRH on the sleep EEG and nocturnal cortisol secretion in healthy volunteers confirms and adds to the results previously observed in animals. On the basis of these findings, we surmise that TRH may contribute to the disturbed sleep continuity seen in depressed patients, probably acting as a cofactor of CRH in a synergistic manner.
Asunto(s)
Ritmo Circadiano/fisiología , Hormona de Crecimiento Humana/metabolismo , Hidrocortisona/sangre , Sueño/fisiología , Hormona Liberadora de Tirotropina/metabolismo , Adulto , Ritmo Circadiano/efectos de los fármacos , Método Doble Ciego , Electroencefalografía/efectos de los fármacos , Humanos , Masculino , Modelos Neurológicos , Hormonas Liberadoras de Hormona Hipofisaria/metabolismo , Valores de Referencia , Sueño/efectos de los fármacos , Estadística como Asunto , Glándula Tiroides/fisiología , Hormona Liberadora de Tirotropina/farmacologíaRESUMEN
The problem of retrieving minor concentrations of constituents by ground-based Fourier-transform infrared emission spectroscopy is addressed by means of the concept of differential optical emission spectroscopy in analogy to the concept of differential optical absorption spectroscopy. Using the prominent nu3 ozone feature at 1043 cm(-1), we show that the strength of the spectral signature depends not only on the amount of ozone but also on the atmospheric thermal structure. This dependence can be described by a rather accurate approximation, which was used to construct a simple diagram to estimate the amount of column ozone between the instrument site and a cloud deck as well as to determine the detection limit. The detection limit is shown to depend on cloud base height. For a given thermal lapse rate it was found that the lower the detection limit, the higher the cloud base altitude. However, as shown in a case study with variable cloud base height, the concept fails for semitransparent clouds. Multiple scattering of the emitted radiation within the clouds yielded a path enhancement that simulated an enhanced amount of constituent. The path enhancement was estimated to be 2.4-4 km at 1000 cm(-1) for low-level clouds, equivalent to an enhancement factor of 6-21. The multiple scattering effect has considerable consequences for ground-based as well as for nadir satellite retrieval techniques in cloudy skies.
RESUMEN
In aging, a decline in sleep continuity, a decreased slow wave sleep, an earlier nocturnal cortisol rise, and a blunted growth hormone (GH) secretion occur. Pulsatile administration of GH-releasing hormone (GHRH) in young controls enhanced slow wave sleep and suppressed cortisol release. We administered GHRH 4 x 50 microg or placebo i.v. to 13 healthy seniors (5 women, 8 men, mean age 69.3 y +/- 8.3 SD). We observed significantly reduced nocturnal awakenings and an increased first non-rapid-eye-movement sleep period. In a subgroup (n = 9), we found a significant activation of GH secretion but unchanged cortisol secretion. Our data underscore that GHRH is capable of promoting sleep in the elderly, but much less than in young subjects. Contrasting to young subjects, the hypothalamic-pituitary-adrenocortical system remains unaffected by GHRH in the elderly. These results provide further evidence that a decrease in the efficacy of GHRH is involved in the biological mechanisms underlying aging.
Asunto(s)
Anciano/fisiología , Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormonas/sangre , Sueño/fisiología , Hormona Adrenocorticotrópica/sangre , Anciano de 80 o más Años , Electroencefalografía , Femenino , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana EdadRESUMEN
When administered intravenously (i.v.) in a pulsatile mode during the first half of the night to young normal controls, growth hormone-releasing hormone (GHRH) results in increased growth hormone (GH) plasma levels and slow wave sleep (SWS) and blunted cortisol release. In the present study we investigated whether GHRH has the same effects when administered in the early morning. Seven normal young male volunteers had 2 sessions each in the sleep laboratory (23.00 to 10.00 h) during which the secretion of GH, cortisol and corticotropin (ACTH) and polygraphic recording were monitored. Verum (4 bolus injections of 50 micrograms GHRH) or placebo were injected i.v. at 04.00, 05.00, 06.00 and 07.00 h. GHRH stimulated GH plasma levels significantly whereas cortisol and ACTH were not altered. In the sleep-electroencephalogram, only rapid-eye-movement density was decreased significantly during the period of active medication; all other sleep parameters were unaffected. We suggest that the physiological occurring high activity of the hypothalamic-pituitary-adrenocortical(HPA) system in the early morning prevents the effects of GHRH on cortisol plasma levels and SWS. Thus GHRH administered to healthy young men in the early morning hours has the same effect as GHRH administered during the first half of the night to patients with major depression who have HPA hyperactivity throughout the day.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Hormona Liberadora de Hormona del Crecimiento/administración & dosificación , Hormona de Crecimiento Humana/sangre , Hidrocortisona/sangre , Sueño/fisiología , Adulto , Ritmo Circadiano , Electroencefalografía , Hormona Liberadora de Hormona del Crecimiento/farmacología , Humanos , Cinética , Masculino , Periodicidad , Sueño/efectos de los fármacosRESUMEN
Centrally administered vasoactive intestinal polypeptide (VIP) promotes rapid eye movement (REM) sleep in rats, rabbits, and cats. We studied the effect of 4 x 10 micrograms VIP (expt 1, n = 7) and 4 x 50 micrograms VIP (expt 2, n = 10) administered hourly as intravenous boluses between 2200 and 0100 on sleep electroencephalogram and secretion of plasma adreno corticotropic hormone, cortisol, growth hormone, and prolactin in humans. In experiment 2, the sleep cycles were decelerated during the first three cycles because of increased duration of both REM and non-REM sleep periods, and there was a tendency to increased REM-to-non-REM ratios. With a low VIP dose, prolactin levels were decreased during the whole night, whereas, with a high dose, they were increased during the first half of the night. In experiment 2, the cortisol nadir was advanced, after midnight the serum cortisol levels were enhanced, and the growth hormone peak was blunted. It appears that VIP may have a phase-advancing effect on sleep cycles and cortisol secretion, possibly through actions that involve the suprachiasmatic nucleus.
Asunto(s)
Hormonas/metabolismo , Caracteres Sexuales , Fases del Sueño/efectos de los fármacos , Sueño REM/efectos de los fármacos , Sueño/efectos de los fármacos , Sueño/fisiología , Péptido Intestinal Vasoactivo/farmacología , Hormona Adrenocorticotrópica/sangre , Adulto , Relación Dosis-Respuesta a Droga , Electroencefalografía , Glándulas Endocrinas/metabolismo , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , Inyecciones Intravenosas , Masculino , Prolactina/sangre , Factores de TiempoRESUMEN
In a 4-week double-blind clinical trial we compared the effects of the tricyclic antidepressants trimipramine and imipramine on the sleep EEG and on nocturnal bormone secretion in 20 male inpatients with major depression. Both treatments produced rapid significant clinical improvement in depression without severe adverse effects. However, the two drugs had markedly different neurobiologic profiles. Trimipramine enhanced rapid eye movement (REM) sleep and slow wave sleep, whereas imipramine suppressed REM sleep and showed no effect on slow wave sleep. Total sleep time and the sleep efficiency index increased under trimipramine but not under imipramine. Nocturnal cortisol secretion decreased with trimipramine but remained unchanged with imipramine. In contrast to imipramine, trimipramine induced an increase in prolactin secretion compatible with its known antagonism at dopamine (D2) receptors. Imipramine induced a decrease in growth hormone secretion during the first half of the night. Neither of the drugs induced significant changes in plasma testosterone concentration. We conclude that trimipramine is an antidepressant with sleep-improving qualities that possibly acts through inhibition of hypothalamic-pituitary-adrenocortical system activity by a yet unknown mechanism.
Asunto(s)
Antidepresivos Tricíclicos/uso terapéutico , Corteza Cerebral/efectos de los fármacos , Trastorno Depresivo/tratamiento farmacológico , Electroencefalografía/efectos de los fármacos , Hormona de Crecimiento Humana/sangre , Hidrocortisona/sangre , Imipramina/uso terapéutico , Polisomnografía/efectos de los fármacos , Prolactina/sangre , Trimipramina/uso terapéutico , Adulto , Anciano , Antidepresivos Tricíclicos/efectos adversos , Corteza Cerebral/fisiopatología , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/psicología , Antagonistas de los Receptores de Dopamina D2 , Método Doble Ciego , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/fisiopatología , Imipramina/efectos adversos , Masculino , Persona de Mediana Edad , Inventario de Personalidad , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/fisiopatología , Receptores de Dopamina D2/fisiología , Fases del Sueño/efectos de los fármacos , Fases del Sueño/fisiología , Testosterona/sangre , Trimipramina/efectos adversosRESUMEN
The neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) play a key role in sleep endocrine regulation. After pulsatile application of GHRH during the first few hours of the night in young normal controls SWS and GH increase, whereas cortisol is blunted. CRH however prompts inverse effects. The balance between these peptides is changed in favour of CRH physiologically during the second time of the night, during the acute episode of depression (due to overactivity of GRH) and in the elderly (due to reduced activity of CHRH). These changes explain the aberrances of sleep endocrine activity in these states, as shallow sleep, low GH and enhanced cortisol.
Asunto(s)
Nivel de Alerta/fisiología , Hormona Liberadora de Corticotropina/fisiología , Hormona Liberadora de Hormona del Crecimiento/fisiología , Hormona de Crecimiento Humana/sangre , Fases del Sueño/fisiología , Trastornos del Sueño-Vigilia/fisiopatología , Adulto , Anciano , Ritmo Circadiano/fisiología , Trastorno Depresivo/fisiopatología , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Polisomnografía , Valores de Referencia , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatologíaRESUMEN
Preclinical data suggest that the imidazodiazepinone derivative bretazenil (Ro 16-6028) has anxiolytic and anticonvulsant properties with only weak sedative effects. We examined the influence of oral administration of 1 mg bretazenil on the sleep EEG and the concomitant nocturnal secretion of cortisol, growth hormone and prolactin in ten healthy young men. After bretazenil we found a significant increase in stage 2 sleep and a significant reduction in stage 3 sleep. REM latency was prolonged. Spectral analysis of sleep-EEG power revealed a decrease in delta and in theta power and an increase in sigma power. We found no significant influence on sleep onset latency or on intermittent wakefulness. Bretazenil prompted a significant decrease in cortisol secretion and a significant increase in prolactin release. It had no major influence on growth hormone secretion.
Asunto(s)
Anticonvulsivantes/farmacología , Benzodiazepinonas/farmacología , Electroencefalografía/efectos de los fármacos , Hormonas/sangre , Sueño/efectos de los fármacos , Adulto , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , Masculino , Prolactina/sangre , Sueño/fisiologíaRESUMEN
In contrast to the effects of GHRH in young normal human subjects, in which repetitive i.v. administration of GHRH prompts an increase in the amount of slow wave sleep (SWS) and in GH secretion and blunting of cortisol release, both in young and in old patients with depression there is no effect on SWS and cortisol release after GHRH, while GH secretion is stimulated. We assume that HPA activity and SWS are inert to the influence of GHRH during acute depression because of a slight CRH overactivity, whereas GHRH exerts effects on GH secretion.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Ritmo Circadiano/efectos de los fármacos , Trastorno Depresivo/sangre , Electroencefalografía/efectos de los fármacos , Hormona Liberadora de Hormona del Crecimiento , Hormona del Crecimiento/sangre , Hidrocortisona/sangre , Fases del Sueño/efectos de los fármacos , Adulto , Anciano , Ritmo Circadiano/fisiología , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/psicología , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Polisomnografía , Fases del Sueño/fisiologíaRESUMEN
Dehydroepi-androsterone (DHEA) exhibits various behavioral effects in mammals, at least one of which is enhancement of memory that appears to be mediated by an interaction with the gamma-aminobutyric acidA (GABAA) receptor complex. We investigated the effects of a single oral dose of DHEA (500 mg) on sleep stages, sleep stage-specific electroencephalogram (EEG) power spectra, and concurrent hormone secretion in 10 healthy young men. DHEA administration induced a significant (P < 0.05) increase in rapid eye movement (REM) sleep, whereas all other sleep variables remained unchanged compared with the placebo condition. Spectral analysis of five selected EEG bands revealed significantly (P < 0.05) enhanced EEG activity in the sigma frequency range during REM sleep in the first 2-h sleep period after DHEA administration. In contrast, the EEG power spectra of non-REM sleep were not affected, nor were the nocturnal time course curves of plasma cortisol, growth hormone, or testosterone concentration. The results suggest that DHEA administration has a mixed GABAA-agonistic/antagonistic effect, exerted either directly or through DHEA-induced changes in steroid metabolism. Because REM sleep has been implicated in memory storage, its augmentation in the present study suggests the potential clinical usefulness of DHEA in age-related dementia.
Asunto(s)
Deshidroepiandrosterona/farmacología , Electroencefalografía , Sueño REM/efectos de los fármacos , Adulto , Hormonas/sangre , Humanos , Masculino , PlacebosRESUMEN
Two dosages (5 mg and 25 mg) of the selective 5HT3 receptor antagonist tropisetron (ICS 205-930) were administered to healthy male controls, and the effects on the sleep EEG and nocturnal secretory activity of growth hormone (GH) and cortisol were evaluated. The lower dosage was administered to four subjects and the higher dosage to eight on 5 consecutive days, preceded and followed by 2 days of placebo treatment. After 25 mg of tropisetron, there was a slight increase in REM sleep in the first part of the sleep period, and stage 2 was decreased during the total night. In addition, plasma cortisol levels increased earlier than under placebo, and plasma GH levels were reduced in the second part of the night. Thus, only discrete effects of tropisetron upon sleep-endocrine activity were noted, making it unlikely that serotoninergic neurotransmission exerts its well-documented effects upon sleep through 5HT3 receptors.
Asunto(s)
Electroencefalografía/efectos de los fármacos , Hormonas/sangre , Indoles/farmacología , Antagonistas de la Serotonina/farmacología , Sueño/efectos de los fármacos , Adulto , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , Indoles/efectos adversos , Masculino , Antagonistas de la Serotonina/efectos adversos , Sueño REM/efectos de los fármacos , TropisetrónRESUMEN
Studies in normal human subjects and animals suggest that the neuropeptide growth hormone-releasing hormone (GHRH) is a common regulator of the sleep EEG and nocturnal hormone secretion. In healthy volunteers GHRH prompts an increase in the amount of slow wave sleep (SWS) and in growth hormone (GH) secretion and blunting of cortisol release. Inhibition of GHRH may contribute to sleep-endocrine aberrances during depression. We tested the effects of pulsatile application of 4 x 50 micrograms GHRH on the sleep EEG and simultaneously investigated nocturnal hormone secretion in 10 inpatients (four females, six males) with the acute episode of major depression. In contrast to the effects of placebo, GH secretion increased distinctly and rapid-eye-movement (REM) density decreased during the second half of night. No other significant changes in sleep-endocrine activity, including SWS, cortisol and ACTH secretion, could be observed. We assume that hypothalamic-pituitary-adrenocortical system activity and slow wave sleep are inert to the influence of GHRH during acute depression. Cortisol and ACTH remained unchanged even in a subsample of five younger (aged 19-28 years) patients. This observation is in contrast to our recent finding that cortisol secretion is blunted in young normal volunteers after GHRH. But on the other hand, GHRH is capable of stimulating GH and inducing a decrease in REM density in these subjects.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Trastorno Depresivo/sangre , Electroencefalografía/efectos de los fármacos , Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/sangre , Hidrocortisona/sangre , Sueño REM/efectos de los fármacos , Hormona Adrenocorticotrópica/metabolismo , Adulto , Anciano , Trastorno Depresivo/tratamiento farmacológico , Método Doble Ciego , Femenino , Hormona del Crecimiento/metabolismo , Hormona Liberadora de Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/fisiología , Placebos , Fases del SueñoRESUMEN
The physiological function of benzodiazepine (BDZ) receptors includes regulation of sleep and neuroendocrine activity. Most of the pharmacological effects of BDZ are blocked by flumazenil. However, recent neurological and behavioral studies suggest that flumazenil has its own central intrinsic activity. This issue was addressed in a study of the sleep EEG and the nocturnal secretion of growth hormone and cortisol in ten normal male controls, who were given flumazenil either alone or in combination with the BDZ agonist midazolam, placebo and midazolam alone. Flumazenil prompted an increase in sleep onset latency, a decrease in slow wave sleep and an increase in wakefulness. Plasma cortisol concentrations after flumazenil administration were lower than after midazolam. Both flumazenil and midazolam decreased nocturnal growth hormone secretion. After simultaneous application of both BDZ receptor ligands the growth hormone blunting was amplified. Our study demonstrates that at the level of the sleep EEG and neuroendocrine activity flumazenil is capable of exerting both agonistic and inverse agonistic or antagonistic effects.
Asunto(s)
Electroencefalografía/efectos de los fármacos , Flumazenil/farmacología , Hormonas/sangre , Sueño/efectos de los fármacos , Adulto , Electrocardiografía/efectos de los fármacos , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , Masculino , Midazolam/farmacología , Vigilia/efectos de los fármacosRESUMEN
The steroid pregnenolone (P) and its sulfate (PS) can accumulate in the central nervous system independent of peripheral sources. Pharmacologically, the sulphated form of P interacts with the GABAA receptor complex, and functional assays show that this steroid behaves as an allosteric GABAA receptor antagonist. The present study explored the effect of a single dose of P upon the sleep-EEG and concurrent secretion of growth hormone and cortisol in male volunteers. P increased the amount of time spent in slow wave sleep and depressed EEG sigma power. Sleep-associated nocturnal cortisol and growth hormone secretion remained unchanged, ruling out the possibility that P exerted its effect via altered regulation of these hormones. Furthermore, results from in vitro studies on the potency of P to activate gene transcription via corticosteroid receptors made a genomic action of P via hormone receptor-sensitive DNA sequences unlikely. We conclude that P acts in a non-genomic fashion at or in the vicinity of the benzodiazepine binding site, modulating allosterically the GABAA receptor like a partial inverse.
Asunto(s)
Electroencefalografía , Pregnenolona/farmacología , Receptores de GABA-A/fisiología , Sueño/efectos de los fármacos , Adulto , Androstanoles/farmacología , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , MasculinoRESUMEN
Adrenal steroid hormones are capable of interfering with a variety of behavioral phenomena including sleep. The mechanisms appear to involve effects at the cell membrane as well as nuclear actions mediated by intracellular mineralo- and glucocorticosteroid receptors (MR and GR). We employed the MR agonist deoxycorticosterone (DOC) and the MR antagonist spironolactone (SP) to study the role of MRs in the regulation of human sleep. We also tested whether the effects of DOC upon the sleep EEG and nocturnal hormone secretion (growth hormone and cortisol) are compatible with those predicted for its major metabolite tetrahydro-DOC (THDOC): electrophysiological and animal experiments had suggested that THDOC would act as a hypnotic via positive modulation of the GABAA receptor. Because neither DOC nor SP affected the sleep EEG substantially, the involvement of MRs in the regulation of sleep needs further study. The sleep-endocrine data showed a suppressive effect of DOC upon plasma cortisol concentrations and an earlier occurrence of nocturnal GH maxima, which can be plausibly explained by GR or sigma receptor-mediated effects. Molecular characterization of DOC and SP confirmed a relatively strong effect of DOC upon transactivation via MR and no effect of SP on the GR-mediated transcription rate. In addition, the possibility that a low dose of the mineralocorticoid DOC may serve as a prodrug for the potential hypnotic THDOC is not supported by the current data.
Asunto(s)
Desoxicorticosterona/farmacología , Hormona del Crecimiento/sangre , Hidrocortisona/sangre , Fases del Sueño/efectos de los fármacos , Espironolactona/farmacología , Adulto , Línea Celular , Humanos , Masculino , Neuroblastoma , Polisomnografía , Receptores de Glucocorticoides/efectos de los fármacos , Receptores de Glucocorticoides/genética , Receptores de Mineralocorticoides/efectos de los fármacos , Receptores de Mineralocorticoides/genética , Fases del Sueño/genética , Fases del Sueño/fisiología , Transcripción Genética/efectos de los fármacos , Transcripción Genética/genética , Activación Transcripcional/efectos de los fármacos , Activación Transcripcional/genéticaRESUMEN
1. The sleep EEG and nocturnal hormone secretion were studied simultaneously in normal male controls and in male patients with major endogenous depression before treatment with tricyclics and after recovery and drug cessation. 2. Several studies were performed in normal male controls to investigate the effect of antidepressants (brofaromine, moclobemide, amitriptyline, clomipramine and trimipramine) and of neuropeptides (CRH and the ACTH (4-9) fragment analog ebiratide) on the sleep EEG and sleep-associated hormone secretion. 3. Elevated cortisol and blunted testosterone secretion are state markers of acute depression, whereas sleep EEG, GH and prolactin variables do not show marked differences between acute depression and recovery. Except for trimipramine, all antidepressants investigated suppress REM sleep. No systematic relationship between the sleep EEG and endocrine effects of antidepressants is detectable. Pulsatile application of CRH in controls mimicks some of the neurobiological symptoms of acute depression. More shallow sleep occurs under ebiratide, whereas hormonal secretion remains unchanged. 4. Our data demonstrate that antidepressants exert distinct effects on sleep. However, these substances do not induce changes in sleep structure which persist after their withdrawal in remitted patients. Pulsatile application of neuropeptides leads to specific effects on CNS activity which are not mediated by changes of peripheral hormone secretion. The view that CRH plays a key role in the pathophysiology of affective disorders is corroborated.
Asunto(s)
Antidepresivos/farmacología , Encéfalo/fisiopatología , Trastorno Depresivo/fisiopatología , Hormonas/metabolismo , Sueño/fisiología , Adulto , Anciano , Antidepresivos/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Electroencefalografía , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción/fisiologíaRESUMEN
When applied centrally to animals, growth hormone-releasing hormone (GHRH) stimulates slow-wave sleep (SWS), whereas somatostatin (SRIF) increases REM sleep. We investigated whether these peptides also affect the sleep EEG in humans when given intravenously by comparing polysomnographically the effects of four boluses of (1) placebo, (2) 50 micrograms GHRH or (3) 50 micrograms SRIF administered at 22.00, 23.00, 24.00 and 1.00 h to 7 male controls. In addition, we collected blood samples through a long catheter every 20 min from 22.00 to 7.00 h and measured plasma cortisol and growth hormone (GH) levels. In comparison with SRIF and placebo, GHRH produced a significant increase in plasma GH concentration throughout the night (mean +/- SD: 10.8 +/- 2.0 ng/ml after GHRH; 3.0 +/- 1.7 ng/ml after SRIF and 3.2 +/- 2.0 ng/ml after placebo). SRIF failed to substantially attenuate the nocturnal GH release. Nocturnal cortisol secretion was blunted after GHRH but remained unaffected by SRIF (61.4 +/- 12.9 ng/ml after placebo; 46.6 +/- 19.7 ng/ml after GHRH and 70.8 +/- 12.6 ng/ml after SRIF). Quantitative sleep EEG staging showed a significant increase in SWS after GHRH administration but no change after SRIF (percent spent in SWS per night: 14.0 +/- 5.6 after placebo, 20.2 +/- 6.6 after GHRH and 15.1 +/- 8.2 after SRIF). Application of SRIF was accompanied by a trend toward increased REM density. The effects of episodic GHRH administration upon SWS, GH and cortisol secretion were opposite to those previously reported for corticotropin-releasing hormone, which supports the view that neuroregulation of human sleep involves an interaction of central GHRH and corticotropin-releasing hormone.
Asunto(s)
Ritmo Circadiano/efectos de los fármacos , Electroencefalografía/efectos de los fármacos , Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormonas/metabolismo , Sueño/efectos de los fármacos , Somatostatina/farmacología , Adulto , Hormona del Crecimiento/metabolismo , Humanos , Hidrocortisona/metabolismo , Masculino , Valores de ReferenciaRESUMEN
The synthetic ACTH/MSH(4-9) analog HOE 427 ("ebiratide"), which is behaviorally the most potent ACTH-derived peptide but which is devoid of endocrine activity, was administered intravenously in a pulsatile mode 4 times (120 micrograms each) at 2200, 2300, 2400 and 0100 to study its effect on the sleep EEG and on concomitant hormonal secretion of cortisol and growth hormone. In comparison to placebo, the peptide produced signs of general activation associated with specific deteriorating effects on the quality of sleep. Sleep onset latency and intermittent wakefulness were increased, slow wave sleep was reduced, but only during the first 3 hours of the sleep period. The nocturnal secretory patterns of cortisol and growth hormone were unaffected by HOE 427. These effects are different from those reported in similar studies in which corticotropin-releasing hormone (CRH) was applied in humans, and they suggest that peripherally administered neuropeptides have specific nonendocrine behavioral effects.