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Biomedical subjects

J Born

Publications and source records attributed to J Born.

At least 91 records · Page 5Linked to original sources
PubMed1998

Angiotensin converting enzyme inhibition by captopril influences cardiac work in healthy hearts.

Although beneficial effects of angiotensin converting enzyme (ACE) inhibition have been demonstrated in ill (ischemic, failing) hearts, it has not been proved that ACE inhibition induces changes in healthy hearts. The question is of clinical relevance, as many hypertensive patients do not display cardiac damage at the onset of treatment with ACE inhibitors, and possible changes in cardiac work might turn out more or less advantageous in the development of hypertensive heart disease. In a refined working heart preparation allowing measurement of cardiac work, including the contribution of atrial work and paracrine cardiac regulation, effects of captopril on cardiac dynamics were assessed. Coronary overflow of bradykinin, norepinephrine, and lactate was measured. Hearts were perfused for 20 min with vehicle or captopril at 3 x 10(-8), 3 x 10(-7), 3 x 10(-6), and 3 x 10(-5) mol/L. At the highest concentration, captopril increased coronary flow. Extending previous studies, the present study demonstrates that, in a concentration-dependent manner, captopril decreased oxygen consumption and maximal left ventricular pressure although the bradykinin outflow was not affected. From these influences of the drug on cardiac work and metabolism in healthy hearts, a protective influence of captopril in acute, critical situations of cardiac malnourishment or cardiac overload may be derived.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Scalp recorded direct current brain potentials during human sleep.

The direct current (DC) potential recorded from the scalp of awake humans has been considered a reflection of general changes in cortical excitability. This study examined DC potential shifts in humans during a night of continuous sleep. Standard polysomnographic recordings and skin temperature were measured simultaneously. Contrary to expectations, average DC potential level indicated higher negativity during nonrapid eye movement (NREM) sleep than REM sleep and wakefulness. Moreover, a dynamic regulation of the DC potential level was revealed in association with the NREM-REM sleep cycle comprising four successive phases: (i) a steep 'NREM-transition-negative shift' during the initial 10-15 min of the NREM sleep period; (ii) a more subtle 'NREM-positive slope' during the subsequent NREM sleep period; (iii) a steep 'REM-transition-positive shift' starting shortly prior to the REM sleep period, and (iv) a 'REM-negative slope', characterizing the remaining greater part of the REM sleep period. DC potential changes were only weakly related to changes in slow-wave activity (r2 < 0.18). The NREM-negative slope and REM-positive slope could reflect, respectively, gradually increasing and decreasing cortical excitability resulting from widespread changes in the depolarization of apical dendrites. In contrast, the NREM-transition-negative shift and the REM-transition-positive shift may reflect the progression and retrogression, respectively, of a long-lasting hyperpolarization in deeply lying neurons.

Adult↗
PubMed1998

Hypothalamus-pituitary-adrenal activity during human sleep: a coordinating role for the limbic hippocampal system.

This review focuses on experiments in humans examining the regulation of the hypothalamo-pituitary-adrenal (HPA) system during nocturnal sleep. The HPA system is a most important mediator of the organism's response to stress. The early phase of nocturnal sleep dominated by extended epochs of slow wave sleep (SWS), is the only time of day in which secretory activity of this axis is subject to a pronounced and persistent inhibition resulting in minimum concentrations of ACTH and cortisol. During late sleep predominated by rapid eye movement (REM) sleep. HPA secretory activity reaches a diurnal maximum. Comparison of the response to administration of exogenous secretagogues of ACTH in men during sleep and nocturnal wakefulness indicated that early sleep, and in particular SWS, is associated with an inhibition of pituitary-adrenocortical responsiveness, which is presumably due to hypothalamic secretion of an as yet unknown release inhibiting factor of ACTH. Pituitary-adrenocortical responsiveness during early sleep was disinhibited after canrenoate which is a selective blocker of mineralocorticoid receptors (MR) located primarily in limbic-hippocampal structures. Hippocampal neuronal networks are known to integrate corticosteroid feedback via both, the MR and the classical glucocorticoid receptor (GR). Prevailing MR related activity in this network seems to act as a trigger for the inhibition of the HPA system. During early sleep, the same hippocampal network appears to be concurrently involved in the formation of declarative memory. Activation of GR after administration of dexamethasone completely blocked the formation of declarative memory during early sleep, indicating that the inhibition of HPA secretory activity is a necessary prerequisite for this memory process. Dysfunction of the described neuro-endocrine mode of regulation during early sleep is present in patients with Cushing's disease, in patients with severe depression and in aged humans. All of these groups show insufficient inhibition of HPA secretory activity particular prominent during early sleep, and reduced SWS in concert with impairments of declarative memory function. First clinical trials suggest that this trias of symptoms may benefit from intranasal treatment with neuropeptides like vasopressin and growth hormone releasing hormone.

Hippocampus↗
PubMed1998

Enhanced selective attention after low-dose administration of the benzodiazepine antagonist flumazenil.

Although recognized for their sedative properties, benzodiazepines are also known to impair sustained and selective attention. Flumazenil at low doses may act to antagonize benzodiazepine-induced effects. This study examined whether low doses of flumazenil would improve event-related brain potential (ERP) indicators of selective attention and induce feelings of activation and anxiety in healthy men. Data from 11 men (24-30 years) who received intravenous flumazenil (0.2 mg, plus 0.3 mg 30 minutes later) and placebo were analyzed according to a double-blind crossover design. ERPs were recorded while subjects performed an auditory selective attention task. Mismatch negativity (MMN), processing negativity (PN), and the P3 component were extracted from the ERP as markers of preattentive mismatch processing, selective attention, and stimulus processing within working memory, respectively. Counting accuracy and performance on a letter cancellation test were used as behavioral indicators of attention. Mood was assessed by an adjective checklist and the State-Trait Anxiety Inventory. Flumazenil significantly increased PN over frontocortical areas, indicating improved selective attention (p < 0.05). Increases in the P3 amplitude and MMN after drug treatment remained nonsignificant. Subjects felt more activated and extraverted after flumazenil treatment than after placebo (p < 0.05). Anxiety was not increased. The findings of this study confirm the concept that flumazenil administered at a low dose in humans exerts effects opposite to those of benzodiazepines.

Adrenocorticotropic Hormone↗
PubMed1998

Influence of exogenous atrial natriuretic peptide on the pituitary-adrenal response to corticotropin-releasing hormone and vasopressin in healthy men.

Atrial natriuretic peptide (ANP) has been considered a potential candidate participating in the inhibitory control of pituitary-adrenal secretory activity. Here, we investigated the influence of ANP, infused at two different doses and over infusion intervals of two different durations, on the release of ACTH and cortisol after stimulation with CRH and with combined administration of CRH and vasopressin (VP). In young healthy men, three experiments were conducted. In Exp I, ACTH/cortisol secretory responses to CRH (50 microg) were examined during and after a 45-min period of ANP infusion at a rate of 4.4 microg/min (starting 15 min before CRH injection). In Exp II, ACTH/cortisol secretory responses to CRH (50 microg) were examined during and after a 90-min infusion period of ANP administered at rates of 4.4 and 8.8 microg/min. In Exp III, ANP was infused at a rate of 4.4 microg/min over 90 min, but instead of CRH, a combined administration of CRH (50 microg) and VP (0.5 IU infused within 5 min) was employed to stimulate ACTH/cortisol release. ANP diminished pituitary-adrenal secretory responses within the first hour after stimulation with exogenous secretagogues. Thereafter, the effect of ANP turned in the opposite direction, with distinctly enhanced concentrations of ACTH and cortisol during the third hour after stimulation. The inhibitory effect of ANP during the first hour of the pituitary-adrenal response was more pronounced on concentrations of cortisol than ACTH and was also more pronounced after combined administration of CRH/VP than after stimulation with CRH alone. Increasing the dose of ANP enhanced the late stimulatory effect on ACTH/cortisol release, thereby terminating the early period of inhibited ACTH/cortisol release more abruptly. The late stimulatory effect was enhanced with prolonged infusion of ANP. In addition, it was associated with reduced hematocrit, increased urine volumes collected, increased heart rate, and enhanced plasma VP concentrations. Together, these changes suggest that the late stimulatory effect of ANP on ACTH/cortisol release reflects an effect secondary to its hypovolemic actions. This stimulatory effect originating from peripheral systemic actions of ANP after exogenous administration appears to override a more direct inhibitory action of the peptide on pituitary-adrenal secretory activity. Therefore, we would expect that with localized release into portal hypophyseal blood the inhibitory component of the action of ANP on pituitary-adrenal secretory activity prevails.

Adrenocorticotropic Hormone↗
PubMed1998

Acute effects of recombinant human interleukin-6 on endocrine and central nervous sleep functions in healthy men.

Interleukin-6 (IL-6) is a proinflammatory cytokine that has been shown to mediate, in addition to immune reactions, various endocrine and central nervous components of the acute phase response. In this context, the present study aimed to specify the contributions of IL-6 to the regulation of pituitary-adrenal secretory activity and GH and TSH secretion, as well as to the regulation of central nervous sleep and mood in healthy men. Effects of a low dose of IL-6 (0.5 microgram/kg body weight) were assessed, inducing plasma IL-6 concentrations closely comparable with those typically observed after infectious challenge. Each of the 16 male subjects participated in two 14-h sessions (between 1800 and 0800 h), receiving either placebo or human recombinant IL-6 sc at 1900 h. Blood was collected repeatedly to determine plasma hormone levels, serum concentrations of cytokines, and C-reactive protein. Moreover, mood was assessed, and sleep recordings were obtained between 2300 and 0700 h. The cytokine induced a prolonged increased in plasma concentrations of ACTH and cortisol (P < 0.001), but led to a decrease in TSH concentrations (P < 0.01). In response to IL-6, subjects reported fatigue and felt more inactive and less capable of concentrating than after placebo. Sleep architecture was altered significantly by the cytokine. Slow-wave sleep was decreased during the first half and increased during the second half of sleep. Rapid eye movement sleep during the entire nocturnal sleep time was significantly decreased. After IL-6, body temperature rose slightly. C-reactive protein concentrations were dramatically increased 12.5 h after substance administration (P < 0.001). IL-6 did not affect serum concentrations of IL-2, IL-8, interferon-alpha, and interferon-gamma. The results underscore the importance of IL-6 in the cascade of cytokines for the neuroendocrine response during the acute phase reaction. In addition, IL-6 appears to be involved in changes of sleep and behavior accompanying infection and inflammatory disorders.

Adrenal Glands↗
PubMed1997

Regulation of human thought by neuropeptide ACTH 4-10: an analysis of the EEG's dimensional complexity.

The neuroactive 4-10 fragment of adrenocorticotropin (ACTH 4-10) has been found to impair electroencephalographic (EEG) signs of selective attention in previous studies. It was hypothesized that this effect reflects a more general influence of the peptide weakening the mutual inhibition among frontocortical neuronal networks. Therefore, ACTH 4-10 was expected to loosen attentional control not only over external input but also over internal thoughts. This study examined the effects of ACTH 4-10 on the dimensional complexity of the EEG recorded while subjects solved tasks of convergent analytical thinking and of divergent creative thinking and during mental relaxation. Subjects were tested 30 min after i.v. administration of placebo or ACTH 4-10 (2 mg). ACTH 4-10 enhanced dimensional complexity of the EEG. The effect primarily concerned frontocortical recordings during convergent thinking, which, following placebo, was associated with the lowest EEG dimension. ACTH 4-10 also impaired behavioral performance on tasks of convergent thought, when presented verbally. Results suggest that ACTH 4-10 counteracts the inhibitory control among cortical neuronal networks necessary for orderly analytical thinking.

Adrenocorticotropic Hormone↗
PubMed1997

Visually-guided saccadic eye movements in adolescents at genetic risk for schizophrenia.

Visually-guided saccades of 21 offspring of schizophrenic parents and 21 individually matched controls were compared with regard to the frequency of occurrence of saccadic hypometria and hypermetria, non-fixations, and omissions of target jumps. Target steps ranged from 10 to 60 degrees, and interstimulus intervals averaged 2.5 s; subjects were promised financial reward depending on performance. Recordings were carried out at the subjects' homes. To screen for cognitive abilities and psychopathological behavior, subjects were tested by means of an intelligence scale and a behavioral checklist. With large target steps (40-60 degrees), the high-risk group made significantly more grossly hypometric saccades (gain < or = 0.8) than the control group; responses to small target steps (10-30 degrees) exhibited a similar, albeit statistically not significant, trend. There were no significant differences with regard to the occurrence of hypermetria. Non-fixations scored marginally higher in the high-risks as compared to controls, but this was again not a significant difference. The incidence of omissions of saccades was very low in both groups. The results of the study suggest that subjects at genetic risk for schizophrenia may differ from controls by an increased incidence of conspicuously hypometric saccades. Clearly, this difference is not caused by a deficit of the saccadic motor circuitry proper; comparison to control data obtained with a similar experimental protocol suggests that it probably reflects an impaired internal control of saccades in the presence of distraction and stress. The relevance of saccades as indicators of a possible schizophrenic vulnerability is discussed.

Adolescent↗
PubMed1997

Effects of sleep and circadian rhythm on human circulating immune cells.

The role of nocturnal sleep for normal immune regulation and its relation to circadian rhythm was examined in 10 men participating in two 51-h sessions. One session included two regular wake-sleep cycles; the other included a night of sustained wakefulness followed by a night of recovery sleep. Blood was collected every 3 h to determine PBMC counts, including the enumeration of monocytes, NK cells, and lymphocyte subsets (CD19+, CD3+, CD4+, CD8+, HLA-DR+). Production of IL-1beta, TNF-alpha, IL-2, and IFN-gamma was determined after stimulation of whole blood samples with LPS and PHA, respectively. Concentrations of IL-6 and cortisol were assessed in plasma. Enumeration of cells indicated significant circadian rhythms for all PBMC subsets under conditions of sustained wakefulness. Compared with sustained wakefulness, nocturnal sleep acutely reduced the numbers of monocytes, NK cells, and counts of all lymphocyte subsets. However, in the afternoon and evening of the day following sleep, counts of NK cells and lymphocytes were significantly higher than after nocturnal wakefulness, indicating that effects of sleep interacted with those of the circadian pacemaker. Sleep markedly enhanced production of IL-2 by T cells (CD3+) but did not influence production of IL-1beta and TNF-alpha, or IL-6 concentrations. Effects of sleep were not mediated by changes in cortisol. The decrease in monocytes, NK cells, and lymphocytes, together with an increased production of IL-2 during sleep, may serve to support ongoing immune defense in extravascular lymphoid tissue during a time of diminished acute Ag challenge.

Adult↗
PubMed1997

Idiopathic hypertrophic cranial pachymeningitis mimicking multiple meningiomas: case report and review of the literature.

A case of idiopathic hypertrophic cranial pachymeningitis with an unusual and misleading manifestation is reported. Computed tomography scan, angiographic and magnetic resonance imaging findings were suggestive of multiple meningeal neoplasms and a correct diagnosis was made only after meningeal biopsy. This 44-year-old patient had a previous history of an ill-defined systemic disorder associating episcleritis, erythroderma nodosa and multiple peripheral arthritis. We review previous reports of idiopathic cranial pachymeningitis with emphasis on radiological investigation techniques, histopathology and possible dysimmune mechanisms of pathogenesis.

Adult↗
PubMed1997

Verbal memory after three months of intranasal vasopressin in healthy old humans.

In animals, evidence has been accumulated that vasopressin (VP) improves learning and memory. In humans, this effect was not consistently demonstrated, and attempts to restore age-related memory deficits by VP also remained inconsistent. Assuming that in old subjects a beneficial effect on memory occurs only after prolonged treatment with VP, we conducted a study in 26 healthy elderly persons receiving 40 IU of VP for three months through the intranasal route. The trial was randomized, placebo-controlled and held double-blind. Memory was assessed by the Auditory Verbal Learning Test (AVLT) requiring the subject to learn repeatedly presented lists of 15 words. Results demonstrated no general effect of long-term treatment with VP on memory in aged humans. However, recall of an interfering word list was improved, indicating a diminished proactive interference by the peptide. Additionally, VP influenced recall depending on the serial position of an item: it improved the primacy effect (i.e. recall of the first words of a list) and impaired the recency effect. This result may indicate an improved semantic encoding (i.e. a primary effect on processes of attention) after long-term administration of VP.

Administration, Intranasal↗
PubMed1997

Slow wave sleep drives inhibition of pituitary-adrenal secretion in humans.

During the first half of nocturnal sleep, the secretory response of the pituitary-adrenal axis to either CRH or vasopressin (VP) administration is reduced. Two experiments were performed aiming (i) to investigate the impact of sleep on the response to a combined CRH/VP administration and (ii) to specify the onset of sleep associated pituitary-adrenal suppression and its relation to specific sleep stages. In experiment I, we compared the effect of simultaneous administration of VP (0.5 IU i.v., within 6 min) and CRH (50 micrograms bolus i.v., in the third min of VP infusion) on the secretion of ACTH, cortisol and GH in healthy men during the first nocturnal epoch of slow wave sleep (SWS) and during nocturnal wakefulness. The increase of ACTH and cortisol concentrations after combined VP/CRH administration was distinctly higher during wakefulness than sleep (P < 0.01). In experiment II, CRH (30 micrograms/h, after an initial bolus of 30 micrograms) was continuously infused in 7 healthy men on 2 nights. On one of the nights, the men were allowed to sleep (between 23.00 h and 05.00 h) after a 3-h period of wakefulness, on the other night they stayed awake throughout the experiment. In both conditions, CRH enhanced ACTH/cortisol plasma levels. Compared with concentrations during continuous wakefulness, sleep and in particular SWS was associated with a suppression of ACTH/cortisol levels (P < 0.05). The findings further support an inhibitory influence of early nocturnal sleep on pituitary-adrenal activity. The effect appears to be strongest during SWS and is probably mediated via hypothalamic secretion of a release inhibiting factor of ACTH.

Adolescent↗
PubMed1997

Systemic immune changes following meal intake in humans.

Food intake represents a high intestinal antigen exposition requiring host defense. Besides local immune activation, this defense includes a coordinate systemic immune response, which may serve to support local immunity. This study examined influences of a standardized high-protein meal on peripheral blood mononuclear cell counts; on the in vitro mitogen-stimulated production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interferon-gamma; on the in vivo plasma levels of tumor necrosis factor-alpha and interleukin-6; and on plasma concentrations of cortisol and growth hormone. Ten healthy men (18-35 yr) participated in two experimental sessions in a balanced order. On one occasion, subjects fasted; on the other, they received a high-protein meal at 1230. Blood was sampled every 15 min. Whereas the numbers of neutrophils and platelets were increased for more than 2.5 h after meal intake (P < 0.01) lymphocyte counts decreased (P < 0.01). Meal intake also decreased the production of interferon-gamma but did not affect the production and plasma levels of the other cytokines. Changes in immune cell distribution and function were accompanied by a strong postprandial rise in plasma cortisol concentrations. Some of the systemic immune changes, like the emigration of lymphocytes, probably into extravascular abdominal tissues, may serve to support local immune defense.

Adult↗
PubMed1997

Cholecystokinin-induced effects on selective attention depend on level of activation.

Cholecystokinin (CCK)-like peptides, such as ceruletide, have been found to improve selective attention as indicated by the processing negativity (PN) of the event-related brain potential. The present study compared effects of ceruletide and placebo after intravenous administration of ceruletide on the PN in healthy subjects classified into two groups scoring high versus low on self-reported activation. Following placebo, PN (at Fz) was somewhat larger in subjects with low than high activation (p < 0.1). Administration of the CCK analog decreased PN in low-activation subjects but increased PN in the highly activated group (p < 0.01). Results suggest that the effects of CCK on selective attention depend on a modulation of central nervous mechanisms underlying activation.

Adult↗
PubMed1997

Evidence for central nervous effects of corticotropin-releasing hormone on gastric acid secretion in humans.

In animals, corticotropin-releasing hormone (CRH) has been shown to decrease gastric acid secretion after intracerebral administration. Evidence exists that in man peptides have a direct access to the brain upon intranasal administration. This study aimed at assessing brain-mediated effects of CRH on gastric pH after intranasal administration in humans. Eleven healthy men were tested on 2 occasions in a double-blind within-subject cross-over comparison during treatment with CRH (versus placebo) administered intranasally at a dose of 20 micrograms every 10 min. Gastric pH values were measured continuously by a gastral pH tube. After 2 h of intranasal treatment, 6 micrograms/kg pentagastrin was injected subcutaneously. The subject's mood was assessed by an adjective list (EWL-N) at the end of each experimental condition. Intranasal CRH increased pH baseline values from (mean +/- SE) 1.70 +/- 0.31 to 2.62 +/- 0.53 (corresponding to 54%), whereas during intranasal treatment with placebo pH values remained unchanged (p < 0.05). After injection of pentagastrin, pH values decreased to 0.73 +/- 0.04 during placebo and to 0.93 +/- 0.14 during CRH treatment (n.s.). During treatment with CRH, subjects felt less tired (p < 0.05) and deactivated (p < 0.05). Plasma cortisol and CRH levels were not affected by intranasal CRH, excluding mediation of the CRH effects via resorption into the bloodstream, and TSH levels were slightly decreased by the end of the treatment. Results confirm the notion of a pathway for CRH from the nose to the brain, initiating, via central nervous mechanisms, inhibition of gastric acid secretion and a change of mood in humans.

Adolescent↗
PubMed1997

Plasma epinephrine and norepinephrine concentrations of healthy humans associated with nighttime sleep and morning arousal.

We assessed the activity of the sympathetic nervous system during undisturbed nocturnal sleep and periods of wakefulness directly before and after sleep in healthy young men. Changes induced by periods of rapid eye movement and by morning awakening, both periods reported to demonstrate an enhanced risk for the onset of cardiovascular diseases, were of particular interest. In 13 healthy men (age, 18 to 35 years), blood for determination of epinephrine and norepinephrine was drawn every 7 minutes between 9:30 PM and 8:30 AM with the subjects resting in a strictly horizontal position. Lights were switched off at 11 PM until awakening at 7 AM. At 8:30 AM, subjects stood up and a final blood sample was drawn. Sleep was monitored somnopolygraphically, and heart rate and blood pressure were continuously measured. Average epinephrine but not norepinephrine concentrations were significantly lower during nocturnal sleep than during wakefulness before and after sleep. In parallel, heart rate and blood pressure declined significantly during sleep. During rapid eye movement sleep, both epinephrine and norepinephrine concentrations were significantly lower than during sleep stages 1 and 2 and slow-wave sleep. Whereas epinephrine concentrations gradually began to increase after morning awakening, norepinephrine levels were not significantly enhanced. However, standing up at the end of the experiment sharply increased norepinephrine concentrations by 180%, whereas epinephrine levels were less enhanced (46%) by the change of body position. This study suggests that the decrease in the activity of the sympathoadrenal branch of the sympathetic nervous system is probably due to an entrainment to the sleep-wake cycle, whereas the low activity of the noradrenergic branches depends mainly on horizontal body position during nocturnal sleep. The activities of the sympathoadrenal and noradrenergic branches of the sympathetic nervous system seem to be downregulated during rapid eye movement sleep. Awakening itself selectively enhances epinephrine levels. Subsequent orthostasis activates both the sympathoadrenal and, most prominently, the noradrenergic branches of the sympathetic nervous system.

Adolescent↗
PubMed1997

Blocking of central nervous mineralocorticoid receptors counteracts inhibition of pituitary-adrenal activity in human sleep.

Pituitary-adrenal activity has been found to be inhibited during early nocturnal sleep in humans. This inhibition was supposed to reflect a regulatory influence of hippocampal cells characterized by the expression of mineralocorticoid receptors (MR). Pituitary adrenal responsiveness to bolus injections of CRH (50 micrograms) was examined in each of nine healthy men on four occasions: CRH was injected either during early nocturnal sleep or at the same time of night while the subject was kept awake. Both of these conditions were run after pretreatment with the selective MR antagonist, canrenoate (2 x 200 mg, 0800 and 1700 h, preceding the experimental night) and after placebo administration. After placebo, sleep reduced ACTH and cortisol secretory responses to CRH to about 65% of the size observed during wakefulness (P < 0.05). After canrenoate, ACTH and cortisol secretory responses during sleep and wakefulness did not differ and were comparable with those obtained in placebo-treated subjects during wakefulness. Compared with placebo, canrenoate also distinctly reduced the time spent in slow-wave sleep (P < 0.005). The findings confirm an inhibition of pituitary-adrenal responsiveness during early sleep. The inhibition disappearance after blockage of MR suggests that sleep exerts this influence via central nervous MR-expressing cells. These cells seem to be simultaneously involved in the generation of slow-wave sleep.

Adrenocorticotropic Hormone↗