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Biomedical subjects

J Born

Publications and source records attributed to J Born.

At least 73 records · Page 4Linked to original sources
PubMed1999

Memory consolidation in human sleep depends on inhibition of glucocorticoid release.

Early sleep dominated by slow-wave sleep has been found to be particularly relevant for declarative memory formation via hippocampo-neocortical networks. Concurrently, early nocturnal sleep is characterized by an inhibition of glucocorticoid release from the adrenals. Here, we show in healthy humans that this inhibition serves to support declarative memory consolidation during sleep. Elevating plasma glucocorticoid concentration during early sleep by administration of cortisol impaired consolidation of paired associate words, but not of non-declarative memory of visuomotor skills. Since glucocorticoid concentration was enhanced only during retention sleep, but not during acquisition or retrieval, a specific effect on the consolidation process is indicated. Blocking mineralocorticoid receptors by canrenoate did not affect memory, suggesting inactivation of glucocorticoid receptors to be the essential prerequisite for memory consolidation during early sleep.

Adult↗
PubMed1999

Dexamethasone blocks sleep induced improvement of declarative memory.

To investigate the role of glucocorticoids for effects of early and late nocturnal sleep on declarative and procedural memory, 2 mg dexamethasone (versus placebo) were administered to healthy men 7 h prior to retention sleep. The retention sleep interval covered either the early or late half of nocturnal sleep. Following placebo, recall of a paired associate list (declarative memory) benefitted more from early than late sleep and recall of mirror tracing skills (procedural memory) benefitted more from late than early sleep. Dexamethasone did not affect slow wave sleep dominating early sleep, but blocked the beneficial effect of early sleep on recall of paired associates. Conversely, dexamethasone reduced rapid eye movement sleep dominating late sleep, but did not affect late sleeps beneficial effect on mirror tracing skills. The natural inhibition of endogenous glucocorticoid secretion during early sleep seems to be essential for a sleep-related facilitation of declarative memory.

Adult↗
PubMed1999

A determinant factor in the efficacy of GHRH administration in promoting sleep: high peak concentration versus recurrent increasing slopes.

A previous experiment indicated a greater efficacy of episodic than continuous growth hormone (GH)-releasing hormone (GHRH) administration in enhancing sleep. The greater efficacy of episodic administration could principally result from two factors, i.e. the greater peak concentration reached after episodic administration or the recurrence of increasing slopes in GHRH concentration. In order to investigate which factor essentially determines the pharmacodynamics of sleep promotion after GHRH, effects after a transient high peak in GHRH concentration were compared with those of repetitive increases in GHRH concentration. Sleep, plasma concentrations of GH, and GHRH were examined in healthy subjects after evening administration of a 'single' i.v. bolus of 50 micrograms GHRH, after five 'repetitive' boluses of 10 micrograms GHRH, and after placebo. Compared with placebo, single GHRH significantly increased time spent in stage 4 sleep (p < .01) and in stage 2 sleep, reduced time spent in wakefulness and onset latency of stage 4 sleep (p < .05, for each), while repetitive GHRH remained without effects. GH secretory activity also tended to be higher after single than repetitive GHRH. Thus, results suggest the relevance of a transiently high concentration of GHRH in blood as an essential factor in enhancing the central nervous sleep process.

Adult↗
PubMed1999

Sleep and endocrine changes after intranasal administration of growth hormone-releasing hormone in young and aged humans.

Systemic administration of growth hormone-releasing hormone (GHRH) has been found to improve human sleep in previous studies. Here we examined effects of GHRH on endocrine function and sleep after intranasal administration, a method which based on previous studies appears to enable a direct effect of peptides on brain function. Also, it was hypothesized that elderly humans displaying deficient GH release and sleep, benefit from GHRH administration more than young subjects. A study was performed according to a double-blind cross-over design. Each of 12 young and 11 old healthy men were intranasally administered with 300 micrograms GHRH (vs. placebo) 30 min before bedtime at 23:00 h. Sleep was recorded polysomnographically until 07:00 h and blood was collected in 15 min intervals for determination of cortisol and GH. Apart from the well-known age-related changes of hormonal secretion and sleep, intranasal GHRH reduced cortisol nadir concentrations in the beginning of sleep (P < 0.05), and also reduced the sleep-induced elevation in GH concentrations during early sleep. Moreover, results indicated that after intranasal administration GHRH increased rapid-eye-movement (REM) sleep and slow wave sleep (SWS), with this influence concentrating on the second half of sleep time. Effects of GHRH did not depend on the subject's age. We conclude that there is a coordinate influence of intranasal GHRH on the central nervous regulation of sleep processes and of hypothalamic-hypophysiotropic secretory activity in both young and elderly men. The effects may mimic the dual neuronal and endocrine function of hypothalamic GHRH activity.

Administration, Intranasal↗
PubMed1999

EEG complexity and performance measures of creative thinking.

The electroencephalogram (EEG) was used because of its dimensional complexity to establish a differentiation of divergent versus convergent thought, considered fundamental modes of cortical processing. In 28 men, the EEG was recorded while solving tasks of divergent and convergent thinking and during mental relaxation. The EEG during divergent thought was compared between subjects achieving high versus low performance scores on this type of task. The dimensional complexity of the EEG was greater during divergent thinking than during convergent thinking. While solving tasks of divergent thinking, subjects with high performance scores had a lower EEG dimension than did subjects with low scores, in particular over frontal cortical areas. The changes were not reflected in single frequency bands of conventional EEG analysis. Based on Hebb's view of neuron assemblies as functional processing units, the higher EEG complexity during divergent than convergent thinking could be the result of the concurrent activation of a greater number of independently oscillating processing units.

Adult↗
PubMed1999

Cytochrome C is released from mitochondria into the cytosol after cerebral anoxia or ischemia.

Mitochondrial dysfunction may underlie both acute and delayed neuronal cell death resulting from cerebral ischemia. Specifically, postischemic release of mitochondrial constituents such as the pro-apoptotic respiratory chain component cytochrome c could contribute acutely to further mitochondrial dysfunction and to promote delayed neuronal death. Experiments reported here tested the hypothesis that ischemia or severe hypoxia results in release of cytochrome c from mitochondria. Cytochrome c was measured spectrophotometrically from either the cytosolic fraction of cortical brain homogenates after global ischemia plus reperfusion, or from brain slices subjected to severe hypoxia plus reoxygenation. Cytochrome c content in cytosol derived from cerebral cortex was increased after ischemia and reperfusion. In intact hippocampal slices, there was a loss of reducible cytochrome c after hypoxia/ reoxygenation, which is consistent with a decrease of this redox carrier in the mitochondrial pool. These results suggest that cytochrome c is lost to the cytosol after cerebral ischemia in a manner that may contribute to postischemic mitochondrial dysfunction and to delayed neuronal death.

Animals↗
PubMed1999

Beneficial treatment of age-related sleep disturbances with prolonged intranasal vasopressin.

Disturbed sleep is common in the elderly and is characterized by disordered sleep architecture with reduced time spent in slow wave sleep (SWS) and in rapid eye movement (REM) sleep. At present, no treatments are available to fully compensate for these disorders. In the elderly, vasopressin content is decreased at various brain sites. Investigating the effects of a 3-month intranasal vasopressin administration on sleep and cognitive functions in two elderly subjects in a foregoing pilot study, the authors found that the most pronounced influence of the peptide was a marked increase in SWS. This placebo-controlled, double-blind, randomized study examined the influences of a 3-month period of daily intranasal vasopressin treatment (20 IU before bedtime and after awakening) on nocturnal sleep in 26 healthy elderly subjects (mean age, 74.2 years). Intranasal treatment of vasopressin increased (1) the total sleep time, on average, by 45 minutes (p < 0.002); (2) time spent in SWS by 21 minutes (p < 0.025); and (3) time in REM sleep in the second half of the night by 10 minutes (p < 0.01). Vasopressin promotes sleep time and improves sleep architecture after prolonged intranasal administration in elderly subjects, although scores of subjective sleep quality did not change. Results suggest that age-related deterioration of sleep architecture can benefit from intranasal treatment with vasopressin. But a potential use in clinical settings will also depend on demonstrating improved subjective sleep quality, which remained unaffected by vasopressin in this study of elderly subjects.

Administration, Inhalation↗
PubMed1999

Brain potentials and attention after acute and subchronic intranasal administration ofACTH 4-10 and desacetyl-alpha-MSH in humans.

Neuropeptides related to adrenocorticotropin (ACTH) are potent regulators of neurobehavioral functions. In humans, ACTH and its behaviorally active fragment ACTH 4-10 have been consistently found to diminish event-related brain potential (ERP) signs of focussing attention. This study aimed at (1) evaluating effects of ACTH 4-10 on ERP indicators of attention in healthy controls after intranasal administration of the peptide. This route of administration has been proposed to provide a more direct access to the brain than the intravenous administration of the peptide, (2) comparing acute effects and effects of a subchronic treatment with ACTH 4-10, and (3) comparing effects of ACTH 4-10 with those of desacetyl-alpha-MSH (corresponding to ACTH 1-13 amide) which like ACTH 4-10 binds to subgroups of the melanocortin receptor family. Double-blind placebo-controlled experiments were completed in 54 healthy young subjects. ERPs were recorded while the subject performed an auditory selective attention task. Moreover, a modified Stroop interference test including motivational (food, sex) and nonmotivational words was performed. Acute intranasal administration of ACTH 4-10 (1 mg) reduced the processing negativity (PN) of the ERP over frontal and central cortical areas (p < 0.05) indicating diminished focussing of attention. Moreover, on this condition subjects were more prone to interference on the Stroop task especially with motivational words (p < 0.05). Subchronic administration of ACTH 4-10 (1 mg/day over 6 weeks) did not affect PN and Stroop performance. Acute intranasal administration of desacetyl-alpha-MSH at equimolar doses (1.68 mg) also remained ineffective. However, some measures of Stroop performance appeared to improve after subchronic desacetyl-alpha-MSH treatment. Results confirm an acute decrease in focussing of attention after ACTH 4-10. These effects of intranasal administration are likely to reflect a direct action of the peptide on respective brain functions. Moreover, they were specific to ACTH 4-10 and were not obtained after equimolar doses of desacetyl-alpha-MSH, thus excluding a mediation via the known melanocortin receptors.

Administration, Intranasal↗
PubMed1999

Protective effect of insulin against hypoglycemia-associated counterregulatory failure.

Antecedent hypoglycemic episodes reduce the counterregulatory neuroendocrine response to hypoglycemia. The role of insulin in the mechanism responsible for the antecedent hypoglycemia causing subsequent counterregulatory failure has not been elucidated. We performed antecedent hypoglycemic clamps (56 mg/dL) lasting 2 h with differing degrees of hyperinsulinemia, which were followed by 6-h stepwise hypoglycemic clamps (76-66-56-46 mg/dL) on the next day. Experiments were carried out in 30 young, healthy men. Fifteen of these subjects were tested on 2 occasions. On 1 occasion the antecedent hypoglycemia was induced by insulin infusion at a rate of 1.5 mU/min x kg (low insulin-ante-hypo); on the other occasion the insulin infusion rate was 15.0 mU/min x kg (high insulin-ante-hypo). Both sessions were separated by at least 4 weeks, and their order was balanced across subjects. The remaining 15 subjects (control group) received the same stepwise hypoglycemic clamp as the other subjects, but without antecedent hypoglycemia. During the stepwise hypoglycemic clamp, the counterregulatory increases in ACTH, cortisol, and norepinephrine were significantly blunted after the low insulin-ante-hypo (P < 0.01, P < 0.05, and P < 0.05, respectively) but not after the high insulin-ante-hypo (P = 0.12, P = 0.92, and P = 0.19, respectively) compared to that in the control group. The cortisol, norepinephrine, and glucagon responses were greater after the high than after the low insulin-ante-hypo (all P < 0.05). In conclusion, the present study clearly demonstrates that even a single episode of mild hypoglycemia reduces neuroendocrine counterregulation 18-24 h later. Insulin has a moderate protective effect on subsequent counterregulation.

Adult↗
PubMed1999

Supraphysiological hyperinsulinemia acutely increases hypothalamic-pituitary-adrenal secretory activity in humans.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in association with hyperinsulinemia is frequently found in patients with type 1 and type 2 diabetes mellitus and in subjects with abdominal adiposity. We questioned whether insulin could cause HPA axis activation and, if so, whether this insulin action may arise at the adrenal level or at a central (i.e. hypothalamic-pituitary) level. Experiments lasting for 6 h each were done in 30 lean healthy men. In 15 men, insulin was infused at a rate of 1.5 mU min(-1) kg(-1). Plasma glucose concentration was held constant during an euglycemic clamp session and was decreased stepwise in a hypoglycemic clamp session. The sequence of the 2 clamp sessions was random, and a 4-weeks recovery period was allowed between the two sessions. The protocol was essentially the same in another 15 men, with the exception that insulin was infused at a rate of 15.0 mU min(-1) kg(-1). During the euglycemic clamp sessions, we found plasma ACTH levels to increase only in the high-, but not in the low-insulin group (group by time interaction, P < 0.01); serum cortisol levels were greater in the high than in the low-insulin group (P < 0.02). In the hypoglycemic clamp sessions, plasma ACTH levels increased in the same pattern in the 2 groups; serum cortisol was greater in the high than in the low-insulin group at the beginning of the clamp (plasma glucose approximately 4.1 mmol/L; P < 0.05). Our results demonstrate that insulin acutely stimulates the HPA secretory activity in humans. The pattern suggests an effect of insulin at both peripheral and central levels of the HPA axis.

Adrenal Glands↗
PubMed1999

Central nervous system effects of intranasally administered insulin during euglycemia in men.

Insulin receptors have been detected in several structures of the brain, yet the biological significance of insulin acting on the brain remains rather unclear. In humans, direct central nervous effects of insulin are difficult to distinguish from alterations in neuronal functions because of insulin-induced decrease in blood glucose levels. Since several intranasally administered viruses, peptides, and hormones have been shown to penetrate directly from the nose to the brain, we tested whether insulin after intranasal administration likewise has access to the brain. After a 60-min baseline period, insulin (20 IU H-Insulin 100 Hoechst) or vehicle (2.7 mg/ml m-Cresol) was intranasally administered every 15 min to 18 healthy subjects according to a double-blind within-subject crossover design. Auditory-evoked potentials (AEP) indexing cortical sensory processing were recorded while the subjects performed a vigilance task (oddball paradigm) during the baseline phase and after 60 min of intranasal treatment with insulin or placebo. Blood glucose and serum insulin levels were not affected by intranasal insulin. Compared with placebo, intranasal administration of insulin reduced amplitudes of the N1 (P < 0.005) and P3 (P < 0.02) components of the AEP and increased P3 latency (P < 0.05). The reduction in P3 amplitude was most pronounced over the frontal recording site (2.42 +/- 1.00 vs. 4.92 +/- 0.79 microV, P < 0.0005). At this site, after insulin administration, a broad negative shift developed in the AEP between 280 and 500 ms poststimulus (area under the curve -166.0 +/- 183.8 vs. 270.8 +/- 138.7 microV x ms after placebo, P < 0.01). The results suggest that after intranasal administration, insulin directly enters the brain and exerts distinct influences on central nervous functions in humans.

Administration, Intranasal↗
PubMed1999

Effects of early and late nocturnal sleep on priming and spatial memory.

A wordstem priming task (nondeclarative memory), and a mental spatial rotation task (declarative memory) were presented to subjects of an experimental "sleep" group (n = 11) and of a "wake" control group (n = 10). Repetition priming effects and recall of spatial memory were tested after 3-hr retention intervals, which followed learning and were placed either in the early or in the late half of the night. Sleep group subjects slept during the retention intervals while subjects of the wake group stayed awake. As expected, early retention sleep was dominated by slow wave sleep (SWS), whereas rapid eye movement (REM) sleep prevailed during late retention sleep. After early retention sleep, recall of spatial memory was superior to that after late retention sleep (p < 0.01), and also to that after retention intervals of wakefulness (p < 0.05). In contrast, priming was more effective after late than early retention sleep (p < 0.05). It appears that early sleep dominated by SWS facilitates consolidation of declarative memory whereas late sleep dominated by REM sleep facilitates consolidation of nondeclarative memory.

Adult↗
PubMed1999

[Attitudes and health status as determinants of participation in individually oriented health promotion].

In a cross-sectional health survey among employees of a large German metal company with 974 study participants, attitudes and aspects of the individual health status were identified which predispose employees to take part in individual health promotion activities. Apart from higher participation rates in women and white collar employees, participants reported on average a less favourable subjective health status, more complaints and diseases, better health related behaviours, and a more intensive utilization of curative and preventive medical services than nonparticipants. Among men, participation in all types of courses increased from the youngest to the oldest group, among women only until the middle-aged groups with a consequent decline thereafter. In men, the image of a person living health-consciously showed the strongest positive association with participation, and not the degree of internal control and responsibility with respect to the maintenance of health or the acquisition and overcoming of disease. The low participation of blue collar workers compared to white collar employees could be attributed to group specific differences in individual health consciousness only to a very small extent. Blue collar participants reported a positive image of a person living health-consciously that was more similar to that of white collar participants than to that of nonparticipants of their own occupational group. Advertisement for health promoting activities should place more emphasis on increasing the image of personal health promotion than on internal control and responsibility for health.

Adult↗
PubMed1998

A study of imidazole-based nuclear magnetic resonance probes of cellular pH.

A number of imidazole-based compounds were tested for their utility as (1)H NMR molecular probes of intracellular pH. Imidazole, previously found useful as a probe of erythrocyte pH, reported a pH in perfused canine glioma cells that was more than 1 pH unit lower than that reported by inorganic phosphate, consistent with the known lysosomal compartmentation of the molecule. Imidazole acetate, also proposed as an NMR probe of cellular pH, was found not to enter the cells of this study. Histidine was found to be readily taken up by cells and reported a pH consistent with that reported by inorganic phosphate. Using the chemical shift of the histidine H2 proton in cells incubated with 10 mM histidine, cellular pH measurements could be obtained in less than 1 s. This compares quite favorably with the measurement time, typically several minutes, needed to assess in vivo pH by (31)P NMR. The use of histidine as a probe of pH is demonstrated in perfused canine and rat glioma cells subjected to ischemia or to low extracellular pH.

Animals↗
PubMed1998

[Eating habits of employees in the metal industry: determinants and patterns].

We conducted a survey on chances and barriers of occupational health promotion and health behaviour including diet in two South German metal companies. Only a small percentage of the 1641 participants consumed healthy food each day, but many avoided eating unhealthy food. Most employees are characterized by a combination of healthy and unhealthy elements. The group of "healthy eaters" consists of more women than men, more older than younger people and more non-manual than manual workers. The level of education and number of children have not been associated with eating habits. Healthy eaters consumed less alcohol and tobacco and were more engaged in sports and in health promotion programmes than unhealthy eaters.

Age Factors↗
PubMed1998

Neuropsychological effects of vasopressin in healthy humans.

Animal research indicated that vasopressin (VP) exerts its principle behavioral influence, the improvement of memory formation, through an action on septo-hippocampal and connected limbic structures. Here human research is reviewed with the notion of a comparable effect of VP in healthy humans. Although the human studies yielded less consistent results than those in rats, they indicate that VP is able to improve declarative memory formation which is the type of memory essentially relying on hippocampal function. The effect appears to center on the encoding process for memory. In examinations of event-related brain potentials (ERPs) VP was consistently found to increase the 'mismatch negativity' (MMN) and the P3 components which are ERP potentials closely linked to the hippocampal processing of novel, unexpected and salient events. Enhanced processing of these stimulus aspects is considered to precipitate memory encoding. The regulation of voluntary selective attention and arousal do not appear to be primary targets of VP effects in humans. A mediation of effects by peripheral changes can be excluded since the central nervous effects were observed in studies using intranasal VP administration providing a direct access to brain functions.

Animals↗
PubMed1998

Intranasal angiotensin II directly influences central nervous regulation of blood pressure.

Intranasal administration of some peptides has been shown to directly influence central nervous functions, thus pointing to a nose-brain pathway for these substances in humans. The present study investigated whether intranasal administration of angiotensin II (ANG II) affects central nervous functions of cardiovascular control in a different way from intravenously administered ANG II. In a balanced cross-over design 12 healthy men were treated with ANG II intravenously (2.5 microg), ANG II intranasally (400 microg), and placebo. Angiotensin II, vasopressin, norepinephrine, and epinephrine plasma levels were assessed every 10 min; blood pressure, heart rate, and systemic vascular resistance were measured by a Dinamap, and by continuous, noninvasive body plethysmography. Also, feelings of activation and mood were measured. Intranasal and intravenous administration invoked equivalent increases in plasma levels of ANG II, and induced an acute rise in blood pressure of comparable size and duration. However, subsequent blood pressure profiles differed dependent on intravenous and intranasal ANG II administration; after intravenous ANG II administration blood pressure remained enhanced at an intermediate level, but it returned to normal or even decreased below normal levels after intranasal ANG II administration. Intranasal ANG II also counteracted the decrease in norepinephrine levels observed after intravenous administration of ANG II. Intranasal but not intravenous ANG II enhanced plasma concentrations of vasopressin. This diverging pattern of effects bears similarities with effects of intracerebroventricular administration of ANG II in animals, suggesting that the effects after intranasal administration reflect a direct central nervous action of ANG II.

Administration, Intranasal↗