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Biomedical subjects

R Pietrowsky

Publications and source records attributed to R Pietrowsky.

At least 37 records · Page 2Linked to original sources

A nose-brain pathway for psychotropic peptides: evidence from a brain evoked potential study with cholecystokinin.

The access of substances to the brain is of particular relevance for the etiology and treatment of psychiatric and neurologic diseases. This study provides functional evidence for a direct access of peptides to the human brain after intranasal administration. Effects were compared of intranasal (IN, 10 micrograms) and intravenous (i.v., 0.25 and 2.5 micrograms) administered cholecystokinin-8 (CCK) on the auditory event related potential (AERP) in 20 healthy subjects. Also, plasma concentration of cortisol and ACTH were monitored. The study was designed as a placebo-controlled, double-blind within-subject cross-over comparison. AERPs were recorded while the subject performed on an attention task (oddball task). Plasma CCK concentrations after IN administration of CCK were comparable to those after i.v. administration of 0.25 microgram CCK, but were substantially lower than those after 2.5 micrograms CCK. The P3 complex of the AERP was markedly increased following the IN administration of CCK (p < .01) compared to placebo and to the i.v. administration of 0.25 microgram. This pattern was more obvious in women than men. Increases in plasma ACTH concentrations after CCK reached significance selectively following the IN mode of administration (p < .01).

Administration, Intranasal↗

Ceruletide improves event-related potential indicators of cognitive processing in young but not in elderly humans.

The effect of intravenously administered ceruletide, a cholecystokinin (CCK) analogue, on neurophysiologic signs of stimulus processing was tested in 16 young (19-28 years) and 16 aged (70-86 years) healthy subjects. Placebo or 2.5 micrograms ceruletide was infused within 30 minutes according to a double-blind within-subject crossover design. Thereafter, auditory event-related brain potential (AERP) responses to stimuli of an "oddball" task (including the random presentation of frequent standard tones and rare target tones) were recorded. Amplitudes of the P2, P3, and SW components of the AERP were reduced in aged subjects (p < 0.05, p < 0.001, and p < 0.01, respectively), and latencies (from stimulus onset) of the N2 and P3 components were prolonged (p < 0.05 and p < 0.01, respectively). Together, these changes indicate impaired cognitive processing capabilities in aged compared with young subjects. Ceruletide enhanced P3 and also the subsequent slow-wave (SW) component that occurs 500 to 700 ms poststimulus in young subjects (p < 0.05 and p < 0.001, respectively). The peptide did not at all affect AERPs in the elderly subjects. Results demonstrate the capability of ceruletide after systemic administration to enhance central nervous system indicators of cognitive processing such as P3 and SW in young subjects. However, despite the clear effect of the CCK analogue in young subjects, it remained ineffective in the group of aged subjects and, thus, failed to compensate for the decline in AERP signs of working memory functioning in the elderly subjects.

Adult↗

The angiotensin converting enzyme inhibitors fosinopril and enalapril differ in their central nervous effects in humans.

BACKGROUND: Although the antihypertensive actions of different angiotensin converting enzyme (ACE) inhibitors are comparable, they may affect central nervous activity, mood and well-being differently. Thus, central nervous actions of ACE inhibitors may represent an essential factor determining compliance with antihypertensive therapy. OBJECTIVE: To compare central nervous effects of the biochemically different ACE inhibitors fosinopril and enalapril in healthy men. METHODS: In a double-blind cross-over study, auditory event-related brain potentials and heart rate variability were assessed 6 h after oral intake of placebo, enalapril (10 mg) and fosinopril (20 mg) with the doses being equipotent with regard to systemic ACE inhibition. Plasma concentrations of noradrenaline, adrenaline, vasopressin and cortisol were determined 3 and 6 h after drug intake. Central nervous effects mediated via direct systemic hypotensive actions were avoided (although not completely ruled out) by including only subjects (n = 14) who displayed no substantial drop in blood pressure following intake of the ACE inhibitors. RESULTS: Enalapril, but not fosinopril, enhanced the N1 component and the N1-P2 amplitude of the event-related brain potential (P < 0.05). In addition, enalapril enhanced plasma noradrenaline concentrations (P < 0.05). A similar effect of fosinopril failed to reach significance. There was no clear-cut effect of ACE inhibition on heart rate variability, and also plasma concentrations of adrenaline, vasopressin and cortisol remained unaffected. CONCLUSION: The results suggest an enhancing effect of enalapril on mechanisms regulating stimulus-induced cortical arousal and central nervous sympathetic outflow. The effects diverging between enalapril and fosinopril indicate that access to human brain functions differs among the various types of ACE inhibitors.

Adult↗

Enhanced psychophysiological signs of attention after angiotensin-converting enzyme inhibition by captopril.

Complementary to its essential role in the central nervous control of cardiovascular activity, the neuropeptide angiotensin II may regulate attentional processes. The present study evaluated central nervous, cardiovascular, and sympathetic indicators of attention after inhibition of angiotensin II synthesis by captopril (50 mg vs. placebo) in 14 men. Event-related potentials (ERPs) and stimulus-related electroencephalographic (EEG) activity were recorded while the subject performed an auditory oddball task. Captopril increased both the N1-P2 component of the ERP (p < .05) and--following the first tone of the task--the EEG desynchronization in the lower alpha frequency band (p < .05). Although blood pressure remained unchanged, heart rate was lowered (p < .05) and plasma norepinephrine concentrations increased (p < .01) after captopril. The effects suggest that inhibition of angiotensin II synthesis enhances an attentional state typically present during sensory intake.

Acoustic Stimulation↗

Improved event-related potential signs of selective attention after the administration of the cholecystokinin analog ceruletide in healthy persons.

Cholecystokinin (CCK) is co-localized with dopamine (DA) in neurons of the mesolimbic-frontocortical dopamine (DA) system, considered essential for the pathology of psychotic behavior and associated attention deficits. The present experiments in 13 healthy men aimed at examining the effects of the CCK analog ceruletide on attention as reflected by event-related brain potentials (ERPs). Subjects were tested according to a double-blind cross-over design on three occasions, following intravenous infusion of placebo, 0.5 microgram ceruletide, and 2.5 micrograms ceruletide. ERPs were recorded during the subject's performance on an auditory selective attention task including the concurrent presentation of frequent standard tones and infrequent deviant tones which the subject had to listen to, or to ignore. The processing negativity (PN) over frontocentral cortical areas, reflecting selective attention, was higher after ceruletide than placebo, this increase being most pronounced after the 2.5 micrograms dose (placebo -1.29 +/- 0.38 microV versus ceruletide -3.02 +/- 0.65 microV, p < .05). ERP signs of a general increase in cortical arousal after ceruletide did not reach significance. Likewise, mismatch negativity, an indicator of preattentive processing of stimulus deviance, was not significantly affected by the peptide. The results indicate that ceruletide affects human brain function primarily by improving selective attention.

Adult↗

Comparison of satiating effects of ceruletide and food intake using behavioral and electrophysiological indicators of memory.

Animal and human studies have suggested a satieting effect of ceruletide, an analog of cholecystokinin. In humans, signs of a selectively diminished central nervous processing of food stimuli may provide a more valid measure of satiety than overt eating behavior. To assess the satieting effects of ceruletide in humans, effects of ceruletide and food intake on memory of food stimuli and stimuli not related to food (neutral and sex) were compared with memory performance in fasted subjects. In experiment I, recall of slide-projected words was tested in 12 fasting men in a within-subject comparison (i) following intravenous administration of saline solution, (ii) of ceruletide (6.75 micrograms), and (iii) after having eaten a regular breakfast. The P3 component of the event-related potential to the stimuli was assessed as a physiological sign of memory processing. In experiment II, recognition of pictures was tested in a between-subject design in 36 fasting men following (i) administration of saline solution, (ii) of ceruletide (6 micrograms), and (iii) intake of an opulent meal. After food intake, recall and recognition of food and also of sex stimuli were diminished, but were increased for neutral stimuli. Ceruletide diminished recognition of food stimuli and increased that of neutral stimuli; similar effects on recall of food and neutral stimuli failed to reach significance. P3 amplitude did not reflect changes in memory performance. Memory of food stimuli declined after ceruletide as well as after food intake, suggesting ceruletide mediates satieting effects on memory processing.

Adult↗

Effects of menstrual cycle on creativity.

Seventeen healthy women (21-31 years) not taking oral contraceptives were tested at three phases of the menstrual cycle distinctly differing in hormonal patterns (menses, preovulatory phase, and midluteal phase). Phase detection was assured by determination of blood hormone concentrations. Another 17 women taking oral contraceptives (combined preparation of estrogen and progestin) served as age-matched controls, and were tested during menses and during phases corresponding to preovulatory and midluteal phase. On each test occasion, aspects of creativity were assessed by a battery of six tests measuring "semantic" and "figural" abilities of divergent thinking. Additionally, a test of motor perseveration (Mittenecker-Zeigeversuch) was presented. During the preovulatory phase, creativity was in general improved when serum concentrations of estrogen (E2) and luteinizing hormone (LH) were highest whereas motor perseveration decreased. In control women, there was no preovulatory improvement of divergent thinking and no preovulatory decrease in motor perseveration.

Adult↗

Effects of vasopressin on event-related potential indicators of cognitive stimulus processing in young and old humans.

BACKGROUND: Vasopressin has been shown to improve electrophysiological signs of cognitive stimulus processing in young human subjects. This study compared the effects of arginine vasopressin (AVP) on central nervous stimulus processing in old and young mentally healthy subjects. To assess aspects of cognitive stimulus processing, event-related potentials (ERPs) were recorded. METHOD: A total of 22 old and 28 young subjects were tested on two subsequent days. Substances were administered intranasally 22, 12, and 1 hour(s) prior to experimental sessions. Prior to the first session, all subjects received placebo. Prior to the second session, 11 of the elderly and 15 of the young subjects received AVP (3 x 10 IU in each nostril) while the remaining subjects again received placebo. The study was held double blind. The subjects performed an auditory "oddball" task consisting of rare target tones (requiring a button press response) interspersed throughout a sequence of frequent standard tones while an electroencephalogram was recorded. RESULTS: Differences between young and aged subjects were more pronounced for ERPs to targets than standard pips. Latencies of the N2 and P3 waves of the ERP to targets were significantly prolonged, and the P3 amplitude was diminished in the elderly subjects (p < .01). N2 amplitude was enhanced in both age groups by vasopressin (p < .05). However, AVP treatment significantly enlarged the N2-P3 difference amplitude only in young subjects. CONCLUSIONS: The results indicate that AVP improves ERP signs of stimulus processing associated with attentional mechanisms. However, the ERP signs of age-related cognitive impairment remained unimproved after AVP.

Administration, Intranasal↗

Effects of insulin and hypoglycemia on the auditory brain stem response in humans.

1. This study aimed to differentiate effects of insulin and hypoglycemia on sensory brain stem functions in humans. Auditory brain stem responses (ABR) were examined in 30 healthy men during euglycemia and after 20 and 50 min of steady-state hypoglycemia of 2.6 mM induced with human insulin (HI) in one session and porcine insulin (PI) in another session. 2. Levels of blood glucose and serum insulin were identical in both sessions during HI and PI infusion. 3. Hypoglycemia increased interpeak latencies III-V (+71 microseconds; P < 0.001) and I-V (+123 microseconds; P < 0.001), whereas changes in the latency of wave I were not significant. 4. After 20 min of constant hypoglycemia, increases in the interpeak latencies I-V and III-V were significantly more pronounced during infusion of PI than HI. These differences disappeared with time spent in hypoglycemia, i.e., after 50 min of hypoglycemia. 5. Apart from the delaying effect of hypoglycemia on neuronal transmission within the sensory brain stem, the results provide evidence for a separate influence of insulin on these functions.

Adolescent↗

Effects of diurnal sleep on secretion of cortisol, luteinizing hormone, and growth hormone in man.

Evidence has been provided for an influence of nocturnal sleep on the secretion of cortisol, LH, and GH in man. Although nocturnal sleep inhibits cortisol secretion during the first hours, it augments the secretion of LH and GH. To separate the effects of circadian rhythm from those of sleep, the present experiments examined the influence of diurnal sleep on the release of cortisol, LH, and GH in 12 young men. Subjects slept on 2 different occasions. After a night of wakefulness, subjects were assigned to bed at 0800 h the following morning. Lights were turned off either at 1100 or 1500 h to enable sleep. Effects of diurnal sleep were evaluated by comparing blood hormone concentrations during the interval from 1100-1500 h between subjects when sleeping and awake. Comparing hormonal concentrations during the 4 h of sleep after 1100 h with those during the 4-h sleep interval after 1500 h provided evidence for an influence of circadian rhythm on cortisol and LH release. Diurnal sleep, as has been shown for nocturnal sleep, augmented the secretion of LH and GH. However, in contrast to nocturnal sleep, diurnal sleep failed to suppress cortisol release, suggesting that sleep does not inhibit cortisol release at any point of its circadian rhythm, but only within a limited range of entrainment.

Adult↗

Evidence for effects of insulin on sensory processing in humans.

Systemic insulin passes the blood-brain barrier and insulin receptors have been detected in various brain regions. Yet, the biological significance of insulin acting on the brain remains rather unclear. Reports of different awareness of hypoglycemic symptoms during hypoglycemia induced by human insulin (HI) and porcine insulin (PI) suggest a modulatory influence of insulin on sensory processing. In a double-blind, within-subject, crossover comparison, we recorded visual-evoked potentials (VEP) in 30 healthy men during euglycemia and after 20 or 50 min of constant hypoglycemia of 2.66 mM (47.9 mg/dl) induced by HI and PI. Blood glucose and serum insulin levels were identical in both sessions. Hypoglycemia reduced amplitudes of the VEP components P1 and N2 and increased latencies of N1, P1, and N2. However, hypoglycemia-induced changes in VEP amplitudes and latencies were significantly stronger during PI and HI infusion: P1-N2 difference amplitude decreased from (mean +/- SE) 11.9 +/- 0.9 to 10.7 +/- 0.8 muV during HI and from 12.4 +/- 0.9 to 8.7 +/- 0.7 muV during PI infusion (P < 0.002). P1 latency increased from 112.0 +/- 3.2 to 118.8 +/- 3.2 ms during HI and from 114.0 +/- 3.3 to 126.3 +/- 4.6 ms during PI infusion (P < 0.05). Differences between the effects of the insulins were consistently apparent after 20 min of hypoglycemia, which indicates a short-term action of the hormone. The results add to those of a foregoing study demonstrating differential effects of HI- and PI-induced hypoglycemia on auditory evoked potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Entrainment of nocturnal pituitary-adrenocortical activity to sleep processes in man--a hypothesis.

The 24 hr patterns of plasma ACTH and cortisol concentrations are characterized by prominent circadian and ultradian oscillations. Usually both, nadir and acrophase of the circadian rhythm occur during sleep. This led us to re-evaluated the temporal relationship between sleep processes and nocturnal plasma ACTH and cortisol levels and the impact of several types of sleep manipulation (sleep delay, sleep disruption, sleep prolongation, sleep deprivation, and reversal of the sleep-wake cycle). Pituitary-adrenocortical activity appeared to be linked to the cyclic process of nocturnal sleep with inhibitory influences present during the first two sleep cycles. After initiation of the third sleep cycle stimulatory effects of sleep prevailed, lasting until awakening. The sleep associated influences appeared to act in concert with influences of circadian oscillators and resulted in an amplification of the circadian rhythm of pituitary-adrenal activity; they were strong enough to entrain the circadian rhythm of the pituitary-adrenal system to the sleep-wake cycle, as long as phase delays were moderate. However, with acute sleep-wake reversals the sleep associated influences were masked by the dominant effects of the circadian clock. In contrast, GH secretion appeared to be controlled primarily be sleep-associated mechanism with only minor circadian influences.

Adrenal Cortex↗

Event-related brain potential correlates of self-reported hunger and satiety.

Perception of hunger and satiety was examined by means of event-related potential (ERP) recordings. On the basis of Helson's frame-of-reference theory, it was hypothesized that hunger is perceived with reference to an actual adaptation level. ERPs were recorded to adjectives (hungry, thirsty, tired) combined with one of five adverbs (very, almost, somewhat, hardly, not). Subjects indicated whether a particular adverb-adjective combination accurately described their actual feeling of hunger, thirst, or fatigue. They were tested after they had fasted for 16 hr and another time when they were satiated. Area of P300 of the ERP was smallest for adverb-adjective combinations agreeing with the subject's actual state of hunger (i.e., adaptation level), which was almost hungry in fasting subjects and hardly hungry in satiated subjects. These P300 minima were flanked by significantly enhanced (p < 0.001) P300 areas for the immediately adjacent adverbs combined with hungry. P300 areas for adverbs combined with thirsty and tired did not depend on the subject's state of hunger. The data suggest that perception of internal states, such as hunger, refers to an adaptation level that is sensitively indicated by P300 area.

Adult↗

Effects of calcitonin on human auditory and visual evoked brain potentials.

Besides its Ca(++)-regulative effects, calcitonin is known to diminish sensitivity to painful stimuli. The present study aimed to clarify whether calcitonin has similar effects on stimulus processing in other modalities. Effects of calcitonin were assessed on brain potentials recorded from the human scalp which were evoked either by auditory clicks or visual checkerboard pattern-reversals. Twelve healthy men were tested in a double-blind intra-subject design receiving either 0.1 IU/kg salmon calcitonin (sCT) or 1.0 IU/kg sCT or saline solution during a 20 min IV infusion. sCT significantly increased latency of wave V of the brainstem auditory evoked potential (BAEP). Effects of BAEP wave V increased in magnitude with increasing dose of sCT and with decreasing intensity of the click stimulus. There was also a slight increase in latency of the N80 of the pattern-reversal visual evoked potential (PR-VEP). Additionally, subjects rated themselves as less activated following the high dose of sCT compared to placebo. The pattern of results is in accord with a slowing or inhibitory influence of calcitonin on auditory and visual sensory processing, thus paralleling findings concerning calcitonin effects on the perception of painful somatosensory stimuli.

Acoustic Stimulation↗

[The effect of "stress hormones" on emotional sensitivity].

Stress is associated with an increased secretion of hormones from the hypothalamus-pituitary-adrenal-axis (HPA-axis). Once released into the blood stream they induce a number of adaptive changes that may also have pertinence to brain functions, resulting, for example in alterations of mood. To provide evidence for a mediation of mood changes by stress related hormone secretion, the influences of a short-term administration of hormones of the HPA-axis on mood and activation were assessed in a total of 182 healthy men (aged between 18 and 34 years in 7 experiments). Effects of intravenously administered hormones on self-perceived mood and activation were assessed by a standardized adjective checklist (Eigenschaftswörterliste) in placebo-controlled, double-blind experiments during rest. Results indicated no effects following corticotropin releasing-hormone or cholecystokinin, but specific effects resulted after vasopressin, oxytocin, ACTH-related hormones, and cortisol. Vasopressin and oxytocin increased activation and attenuated arousal and anger, ACTH-related hormones increased sensitivity and diminished extraversion, while cortisol increased activation and concentration. It is concluded that hormones of the HPA-axis specifically affect mood and activation. The pattern of hormonal changes in mood may have adaptive functions by preparing for behavioral and cognitive coping with stress.

Adult↗

Brain evoked responses, a bioassay for central actions of adrenocorticotropin (ACTH 1-39) and corticotropin releasing hormone (CRH) in humans.

Blood borne hormones of the hypothalamus-pituitary-adrenal (HPA) axis form an afferent humoral system modulating a great variety of brain functions. In humans, bioassays consistently reflecting central nervous system actions have not been developed, so far. The present experiments are part of a series of studies which have been conducted to demonstrate the afferent influences of ACTH and CRH on brain activity by recording of auditory event-related brain potentials (ERPs) in healthy human subjects. In a double-blind within-subject comparison in 12 healthy male students, influences of 4 U ACTH and 100 micrograms CRH (infused within 2 h; the infusion starting 1 h prior to ERP recordings) were compared with the effects of a placebo infusion. Influences of the hormones were tested for the early, brain stem generated ERP components (BAEPs) and for the late components of the ERP associated with cortical stimulus processing. ACTH and CRH showed no consistent effect on BAEPs. ACTH, but not CRH, significantly reduced amplitudes of late ERP components, in particular, the Nd and P3 components which are considered signs of selective attention. These results are consistent with findings from previous studies demonstrating impaired ERP signs of selective attention in humans after administration of the 4-10 fragment of ACTH which lacks the peripheral adrenocorticotropic activity. Together with these foregoing studies, results from the present experiments further establish ERP methodology as a sensitive bioassay for CNS actions of hormones in humans.

Adrenocorticotropic Hormone↗

Sleep-associated augmentation and synchronization of luteinizing hormone pulses in adult men.

We reinvestigated the temporal relationship between sleep and LH secretion in healthy adult males by comparing LH secretion patterns during sleep with those during the 6 h of wakefulness preceding the sleep epoch. Sleep stages were determined by somnopolygraphy. In these subjects LH secretion was augmented during sleep as indicated by increased mean LH concentrations and increased pulse amplitudes; pulse frequency was not different. In addition, LH secretion appeared to be synchronized to the NonREM-REM sleep cycles: initiation of LH pulses occurred preferentially in the mid-portion of a NonREM-REM cycle during Non-REM sleep. Thus, REM sleep was almost uniformly associated with decreasing LH concentration. These findings demonstrate that patterns of LH secretion characteristic for early puberty are principally present also in adult males.

Adult↗

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↗