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Biomedical subjects

R Pietrowsky

Publications and source records attributed to R Pietrowsky.

51 records · Page 3Linked to original sources

Influences of peripheral adrenocorticotropin 1-39 (ACTH) and human corticotropin releasing hormone (h-CRH) on human auditory evoked potentials (AEP).

Hormones of the hypothalamus-pituitary-adrenal (HPA) axis have been considered to form part of an efferent humoral system modulating central nervous stimulus processing. The present experiments were designed to compare the effects of iv bolus administrations of placebo, porcine ACTH 1-39 (1.5 U) and h-CRH (25 micrograms) on auditory evoked potentials (AEPs) in healthy men. Also, cardiovascular parameters, cortisol and self-reported mood were assessed. ACTH significantly reduced the amplitude of the N1 component of the AEP; P1 and P2 remained unchanged. The selective reduction of N1 amplitude defies an interpretation of the changes in terms of a reduced stimulus-induced cortical arousal following ACTH; the ACTH-induced changes may rather indicate an influence on frontocortical functions of directing attention. The effect of ACTH on N1 cannot be attributed to its adrenocorticotropic action or to cardiovascular changes, but appears to represent an intrinsic extraadrenal influence of the hormone. The data do not provide evidence for effects of h-CRH on central nervous stimulus processing in humans, after peripheral administration.

Adrenocorticotropic Hormone↗

Influences of the cholecystokinin analog ceruletide on human sleep and evoked potentials.

Two experiments are reported, investigating the effects of the cholecystokinin analog ceruletide on central nervous activation in man. In experiment I, 0.55 micrograms/h ceruletide was infused at a constant rate during the night to study its effects on spontaneous EEG activity during sleep. In experiment II, we examined the effects of a bolus injection of ceruletide (0.5 micrograms) on components of the auditory evoked potential reflecting exogenously provoked central nervous arousal. While ceruletide had no effect on sleep, it attenuated stimulus-induced cortical arousal.

Adult↗

Time course of ACTH 4-10 effects on human attention.

Previous studies have demonstrated that the adrenocorticotropic hormone (ACTH) and its 4-10 fragment are potent modulators of attention in humans. In these studies the Nd component ('negative displacement') of the stimulus-evoked brain potential (event-related potential, ERP), which is a neurophysiological indicator of selective attention, proved most sensitive to effects of these peptides. The Nd decreased in amplitude linearly with logarithmically increasing doses of ACTH 4-10 applied. Here we report results complementing these previous findings by establishing a time course of the effects of ACTH 4-10 on human attention. In a double-blind cross-over study, attention performance on a dichotic listening task was tested in 18 healthy volunteers, after having received intravenously either placebo or 1 mg ACTH 4-10. Tests took place 0, 30, 90, 180, 330, 600 min, 24, 48 and 72 h after drug intake and took about 15 min. Each subject was tested on 4 of these occasions, selected according to a random schedule. During task performance ERPs to the different task stimuli were recorded. ERPs were used to determine the Nd (an indicator of controlled processing of stimuli which the subjects selectively attended to) and the mismatch negativity (MMN) reflecting automatic processing of stimulus deviance. ACTH 4-10 diminished the Nd significantly at 30 min after treatment administration. On none of the other occasions significant changes in Nd occurred. MMN was not affected by the peptide. The results indicate a short-term action of ACTH 4-10 on selective attention, which takes about 30 min to develop and does not last longer than 90 min after treatment.

Adrenocorticotropic Hormone↗

Fragments of ACTH affect electrophysiological signs of controlled stimulus processing in humans.

It has been proposed that the systemic administration of the 4-10 fragment of ACTH in humans affects primarily attention. In the present study, influences of ACTH 4-10 on event-related potential (ERP) indicators of attention were evaluated in healthy men. The influences were compared with those of an analog of the ACTH 4-9 sequence (HOE 427) which was expected to have an increased potency. Following an adaptation session, each of 20 healthy men was tested on four occasions in a double-blind study designed according to a latin-square. On each occasion, subjects received (iv) one of the following treatments: placebo, ACTH 4-10 (1 mg), HOE 427 (60 micrograms) and HOE 427 (200 micrograms). Treatments were administered 40 min prior to recordings of ERPs. ERPs were recorded while the subjects performed on a dichotic listening task paradigm. The various tone pips presented in this task elicit ERPs providing measures of controlled stimulus processing (Nd reflecting selectivity of attention, and P3) and automatic processing of stimulus deviance (mismatch negativity). ACTH 4-10 as well as 200 micrograms HOE 427 reduced Nd and also P3 amplitudes following attended stimuli. Smaller (non-significant) changes in the same direction were observed following 60 micrograms HOE 427. The results suggest an impairing influence of ACTH 4-10 and of HOE 427 on signs of controlled stimulus processing, particularly on the Nd. The analog appeared to be more potent than the endogenous 4-10 fragment.

Adrenocorticotropic Hormone↗

Effects of cholecystokinin and calcitonin on evoked brain potentials and satiety in man.

Central nervous effects of the peptides cholecystokinin (CCK) and calcitonin (CT) were tested in an attention task for their effects on Auditory Event Related Potentials (AERPs) and for their effects on satiety and activation as measured in self-rating scales. Thirteen healthy subjects received either 3 IDU/kg bodyweight CCK 1-33, 0.1 IU/kg bodyweight CT and placebo according to a double-blind within-subject cross-over design. Subjects had fasted for at least 16 hr prior to the experiment. CCK induced the feeling of satiety after stimulation with the preparation of a meal. The peptides prevented an attenuation of the N2-component of the AERP after the preparation of a meal, indicating that the subjects were less distracted by the food cues. The results suggest that the central nervous effects of CCK and CT may constitute an aspect of satiated behavior.

Adult↗

The influence of a vasopressin-analogue (DGAVP) on event-related potentials in a stimulus-mismatch paradigm.

To assess the influence of DGAVP (des-glycinamide-arginine-8-vasopressin, a synthetic vasopressin analogue) on the processing of stimuli and stimulus deviance in humans in a double-blind cross-over experiment, 13 subjects received 60 IU DGAVP versus placebo intranasally 48, 24, and 1 h prior to the experimental session. Auditory event-related potentials (ERPs) were taken as a tool to investigate central nervous processing in an experimental task that required the subjects to count different kinds of rare tone pips deviating in pitch and probability compared to frequent standard tones. Direction of attention was manipulated by instructing the subject to count a different class of deviating tone pips in each attention condition. DGAVP enhanced the N2 of the ERP to tone pips deviating extremely in pitch from standard tones, whether or not the extremely deviating pips were to be attended to by the subjects. This influence suggests an intensified mismatch processing under DGAVP that may result from a general excitatory effect of this substance on cortical activity.

Administration, Intranasal↗

Influences of cortisol on auditory evoked potentials (AEPs) and mood in humans.

The present study was designed to investigate effects of cortisol on evoked potential indicators of sensory processing and on mood in 45 healthy human subjects. In order to determine the glucocorticoid effect to be primary excitatory or inhibitory, the vertex potential components. (P1, N1, P2) of the auditory evoked potential (AEP) were assessed, which also indicate a stimulus-induced cortical arousal response mediated by the nonspecific sensory system of the reticular formation. The AEPs were recorded while the subject performed a vigilance task containing 8 blocks of monotonous series of tone pips presented at different interstimulus intervals. Mood was assessed by an extensive adjective checklist. Experiments were held double-blind and designed as between-group comparison. Subjects received either 40 or 20 mg hydrocortisone (constantly infused between 35 min prior to testing till the end of the experiment), or placebo. Enhanced plasma cortisol levels were related to increased amplitudes of the AEP vertex response. Furthermore, cortisol augmented self-reported concentration and reduced tiredness during task performance. The glucocorticoid effects on both AEPs and self-report measures suggest an excitatory influence of cortisol on brainstem and thalamic mechanisms mediating the stimulus-induced cortical arousal.

Adolescent↗

Neurophysiological effects of recombinant interferon-gamma and -alpha in man.

Treatment of malignant tumors with interferon (IFN) is in some patients accompanied by serious neurological side effects. The present study assessed neurophysiological changes in spontaneous EEG activity, visual-evoked cortical potentials (VEPs), and brainstem auditory-evoked potentials (BAEPs) during IFN-gamma or IFN-alpha therapy in 9 patients. In addition, blood pressure, heart rate and body temperature were monitored. In all sessions under IFN, the latency of the P100 component of the VEP was shortened as compared to baseline conditions. IFN also reduced latencies of BAEP components, and diminished amplitudes of the spontaneous EEG activity within the alpha and beta frequency band. These latter effects were somewhat less consistent than those on VEPs. The major neurophysiological changes appeared to be similar for IFN-gamma and IFN-alpha. The results are in accord with an excitatory effect of IFN on central nervous activity. The magnitude of changes excludes a neurotoxicity of IFN-gamma or IFN-alpha at the doses used in this study.

Adult↗

Stimulation of the pituitary adrenocortical system in man by cerulein, a cholecystokinin-8-like peptide.

The responses of plasma adrenocorticotropin hormone (ACTH) and cortisol to intravenous injection of cerulein (ceruletide), a decapeptide closely related to cholecystokinin octapeptide, were investigated in healthy men. In response to 16 ng/kg cerulein, plasma ACTH rose from a preinjection level of 42 +/- 11 pg/ml (mean +/- SEM) to a peak level of 81 +/- 16 pg/ml after 15 min. This ACTH increase was followed by a rise in plasma cortisol from a preinjection value of 10.3 +/- 0.9 microgram/dl to a peak value of 17.7 +/- 1.7 microgram/dl after 30 min. This is the first report of the potent stimulating effect of a cholecystokinin-8-related peptide on the pituitary-adrenal system in man.

Adrenal Cortex↗

Glucocorticoid influences on the auditory brain-stem responses in man.

The present study was designed to test whether human auditory brain-stem responses (ABRs) are sensitive to peripheral endocrine signals as reflected by changes in the plasma glucocorticoid concentration. ABRs were recorded following treatment with 50 mg hydrocortisone or placebo in 13 healthy male adults. Experiments were double-blind and designed according to a latin-square within-subject comparison. Treatment was applied 1 h prior to testing as an i.v. infusion over a period of 20 min. Subjects were tested in each session under 3 X 3 conditions, i.e., ABRs were obtained to series of clicks presented at 3 different intensities (80, 60, 40 dB HL) and with 3 different stimulus rates (39, 10, 5 clicks/sec). Additionally, oral temperature was monitored. Hydrocortisone significantly reduced latencies of waves III, V, and VI (and subsequent negative troughs) when low stimulus intensities were used. Furthermore, the glucocorticoid reduced latencies of waves Vn, VI and VIn when the clicks were presented at a slow stimulus rate. Further studies have to specify the underlying mechanisms of these changes.

Adult↗

Effects of DGAVP on verbal memory.

Effects of DGAVP (desglycinamide-arginine-vasopressin, a synthetic vasopressin analog) on verbal memory were investigated in 13 healthy male volunteers. Ten word lists, each consisting of 15 words, were presented to the subjects who had to recall them according to a free recall paradigm. The total number of recalled words was not different between DGAVP and placebo treatment; but DGAVP had an effect on memory performance depending on the serial position of the words. It attenuated the primacy effect and enhanced the recency effect of memory performance. The pattern of changes after DGAVP may be consistent with an effect of the peptide on general arousal. Since the experiment was not designed to test influences of DGAVP on arousal, these considerations remain tentative.

Adult↗

Vasopressin and oxytocin do not influence early sensory processing but affect mood and activation in man.

Effects of arginine-vasopressin (AVP) and oxytocin (OX) on brainstem and middle latency auditory-evoked potentials (BAEP and MAEP), reflecting early sensory processing within the specific auditory pathways and primary auditory cortex, were investigated. Additionally, subjects rated their feelings of activation and mood on an adjective check list (EWL). The experiments were undertaken in 12 healthy male volunteers, receiving either placebo, 0.15 IU AVP, 0.5 IU AVP or 0.5 IU OX as IV bolus injection according to a within-subject double-blind design. There were no consistent effects of AVP and OX on BAEPs and MAEPs. AVP decreased self-perceived deactivation, fatigue and arousal. Results do not suggest an effect of AVP and OX on early stages of sensory processing, but, consistent with previous studies, demonstrate changes towards increased (self-perceived) general activation following administration of these hormones.

Adult↗

Selective influence of menstrual cycle on perception of stimuli with reproductive significance.

Sixteen healthy women (20-32 years) not taking oral contraceptives were tested at three phases of their menstrual cycles (menses, preovulatory phase, and midluteal phase). Another 16 women taking oral contraceptives served as age-matched controls, and were tested during menses and during phases corresponding to the preovulatory and midluteal phase. On each test occasion, perception was assessed of visual stimuli belonging to three categories: sex (nude men), babies, and stimuli related to body care. Also, meaningless syllables were given. Stimuli were presented by a tachistoscope. Presentation of each stimulus was repeated until the subject signaled recognition. Trials to recognition and correctness of the recognition response were recorded. In spontaneously cycling women effects of the phase of the menstrual cycle depended on the stimulus meaning: During the preovulatory phase, there was an increase in the number of correctly recognized sex stimuli (p < 0.05) and of stimuli falsely recognized as sex stimuli (p < 0.05). The number of stimuli falsely recognized as body care was reduced during this phase (p < 0.05). Moreover, during the luteal phase, the number of trials to recognition of baby stimuli was diminished (p < 0.01). In women taking contraceptives, no stimulus specific changes occurred, but correct recognition was generally improved during the luteal phase. Rather than supporting a general influence of the normal menstrual cycle on perceptual functions, the present results demonstrate that the effects of the menstrual cycle depend on the meaning of the stimulus with the perception of sexual stimuli, but not of stimuli related to maternal nurture, being improved during the preovulatory phase.

Adult↗

Effects of sleep on the production of cytokines in humans.

The restorative functions of sleep may affect immunologic functioning. The present study examined the effects of sleep on stimulated cytokine release in 13 healthy men. The subjects spent 2 experimental nights in the sleep laboratory. In one condition, lights were turned off at 11:00 PM to enable sleep for 3.5 hours. Thereafter, they stayed awake till 7:00 AM. In the other condition, conversely, subjects stayed awake between 11:00 PM and 3:00 AM. Then, lights were turned off for a 3.5-hour phase of sleep. Blood was sampled every 30 minutes between 11:00 PM and 7:00 AM. Sleep was monitored by polysomnographic recordings. Release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) was determined after stimulation of mononuclear cells with lipopolysaccharide from Escherichia coli. The release of IL-2 was stimulated with phytohemagglutinin. Compared with wakefulness, after 3 hours of sleep, production of TNF-alpha and IL-1 beta was substantially diminished (p < .01). Production of IL-2 was enhanced during sleep (p < .05), with this effect being limited to the second nocturnal sleep phase after 3:00 AM. Sleep-dependent changes in stimulated cytokine release were independent of changes in plasma cortisol concentrations. These results indicate a specific reducing effect of sleep (vs. wakefulness) on cytokine production by monocytes (TNF-alpha and IL-1 beta). The rather slow development of the effects calls for further studies to establish the exact time course of the influence of sleep on cytokine production.

Adult↗