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Biomedical subjects

K H Voigt

Publications and source records attributed to K H Voigt.

At least 19 recordsLinked to original sources

Sympathetic activity is reduced by nCPAP in hypertensive obstructive sleep apnoea patients.

There is increasing evidence that nasal continuous positive airway pressure (nCPAP) lowers blood pressure in obstructive sleep apnoea (OSA) patients, not only during sleep but also in the daytime. However, both the mechanisms of blood pressure reduction and the considerable differences in the magnitude of the effect in the studies presented to date are not fully understood. Therefore, the authors prospectively studied the effect of nCPAP on noradrenaline plasma levels (NApl), blood pressure and heart rate (HR) in 10 normotensive and eight hypertensive OSA patients before and after 41.6 +/- 16.9 days of nCPAP therapy. Polysomnography and invasive blood pressure were continuously monitored over 24 h in the supine position before and with nCPAP. NApl were analysed every 15 min. In hypertensives, nCPAP reduced NApl by 36 +/- 25%, lowered mean arterial blood pressure substantially (night-time: -8.89 +/- 14.09 mmHg; daytime: -7.94 +/- 10.47 mmHg) and decreased HR by 6.6 +/- 5.4 beats x min(-1), whereas in normotensives there were only minor changes. The decrease in heart rate was associated with a decrease in mean arterial blood pressure and noradrenaline plasma levels, suggesting a causal effect of nasal continuous positive airway pressure therapy. This nasal continuous positive airway pressure effect occurs mainly in hypertensive obstructive sleep apnoea patients, whereas the effect is small in normotensives. This may explain, at least in part, some of the discrepant results in previous treatment studies.

Adult↗

Expression and distribution of calcitonin receptor-like receptor in human hairy skin.

Calcitonin gene-related peptide and adrenomedullin exert potent effects in skin but their cellular targets are unknown. This study aimed to identify the cellular location of calcitonin receptor-like receptor (CRLR) which is pharmacologically identical to CGRP receptor-1, a putative molecular target of CGRP and adrenomedullin. RT-PCR analysis of human hairy skin revealed the presence of CRLR mRNA and immunohistochemical analysis, employing a previously characterized polyclonal antibody raised to CRLR, provided novel evidence of the cellular distribution of CRLR. Extensive and specific CRLR-immunostaining was detected in arteriolar smooth muscle and venular endothelium and is consistent with CGRP's putative role in neurogenic inflammation. Novel targets for CGRP and/or adrenomedullin were identified, including capillary endothelium, hair follicles and sweat glands.

Adrenomedullin↗

Cortisol mediates redistribution of CD8+ but not of CD56+ cells after the psychological stress of public speaking.

The present study investigated the question if a pharmacological blockade of cortisol release with stress affects lymphocyte redistribution in healthy volunteers. It was expected that the well known increases in the number of CD8+ (T-suppressor/cytotoxic cells) and CD56+ (natural killer cells) after stress would not be downregulated in the absence of an appropriate cortisol response, since redistribution is markedly influenced by glucocorticoids. In a double blind design, forty healthy male volunteers were exposed to a brief psychological stressor (public speaking) and received a single oral dose of dexamethasone [DEX] (N=20) or placebo (N=20) the evening before the main experiment. Ratings on emotional states and blood samples for determination of hormones, CD8+, and CD56+ cell counts were obtained at different time points during the experiment. Stress of public speaking led to highly significant increases in catecholamine and cortisol concentrations, to subjective discomfort and, most pronounced, to high increases in the number of CD8+ and CD56+ cells. DEX neither influenced baseline levels of mood, catecholamines and cell numbers nor stress induced responses of mood and catecholamines. However, during the whole experiment cortisol concentrations were suppressed in the DEX-condition and the number of CD8+, but not CD56+, cells remained elevated at the end of the session, while in the placebo condition the numbers of these cells were decreased to baseline levels. The data demonstrate that cortisol seems to play an important role in stress induced redistribution patterns of CD8+ but not CD56+ cells. This, however, can be explained by different migration processes between those cells (e.g. different targets of migration) and, therefore, different glucocorticoid influences on target tissues.

Adult↗

Linking sociological with physiological data: the model of effort-reward imbalance at work.

While socio-epidemiologic studies documented impressive associations of indicators of chronic psychosocial stress with cardiovascular (c.v.) disease evidence on patho-physiologic processes is still limited. In this regard, the concept of heightened c.v. and hormonal reactivity (RE) to mental stress was proposed and explored. While this concept is a static one we suggest a more dynamic two-stage model of RE where recurrent high responsiveness (stage 1) in the long run results in attenuated, reduced maximal RE due to functional adaptation (stage 2). We present results of an indirect test of this hypothesis in a group of 68 healthy middle-aged men undergoing a modified Stroop Test: in men suffering from high chronic work stress in terms of effort-reward imbalance significantly reduced RE in heart rate, adrenaline and cortisol was found after adjusting for relevant confounders. In conclusion, results underscore the potential of linking sociological with physiological data in stress research.

Humans↗

Alterations in the pituitary-adrenal axis of adult mice following neonatal exposure to interleukin-1.

Interleukin-1 (IL-1), a cytokine mainly derived from activated cells of the macrophage lineage, can stimulate the hypothalamus-pituitary-adrenal (HPA) axis. Acute and long-lasting effects on the HPA axis were induced by the administration of low doses of IL-1 to mice during the first 5 days of life. In 5-day-old mice, corticosterone blood levels were markedly elevated 2 h following the last injection of IL-1. IL-1-treated mice grew normally. When studied during adulthood, however, these animals showed a reduction in morning values of corticosterone and the ACTH/corticosterone ratio was increased. Furthermore, an inverse correlation between ACTH and corticosterone levels in blood and between ACTH content in the pituitary gland and corticosterone levels was observed in IL-1-treated mice. Lower blood levels of corticosterone were not due to a reduced sensitivity of the adrenal glands, because these animals responded normally to exogenous ACTH. Another alteration observed in IL-1-exposed adult mice was a reduction in ACTH-like immunoreactivity in the pituitary gland following acute cold and restraint stress. It is concluded that exposure of mice to IL-1 early in life causes long-lasting alterations in the HPA axis. Spleen cells from adult mice treated with IL-1 at birth also developed a stronger response to allogeneic antigens than did cells from control mice. This observation indicates the relevance of immune-neuroendocrine interactions during development.

Adrenocorticotropic Hormone↗

Actions of dalargin upon single unit activity in the ampullae of Lorenzini of the skate Raja clavata.

In the present study we have shown by single afferent unit recording in electroreceptors of skates (the ampullae of Lorenzini) that the synthetic analogue of leu-enkephalin, dalargin (DAL) at concentrations between 10(-6)-10(-10) M cause a concentration-dependent decrease in the resting discharge frequency as well as a decrease in stimulus evoked responses. The specific opiate antagonist naloxone (NAL, 10(-6) M) antagonizes responses induced by DAL. DAL depresses the excitatory action of L-glutamate (L-GLU). The data obtained speak in favour of the presence of opiate receptors at the synaptic membrane of the ampullae of Lorenzini.

Animals↗

Methionine5-enkephalin and opiate binding sites in the neurohypophysis of the bird, Gallus domesticus.

Uncertainties with respect to the cellular localization, binding characteristics and function of Met-enkephalin in the neurohypophysis of mammalian species prompted us to examine the neurohypophysis of a non-mammalian species for opioid material and opioid binding sites. In extracts of the neurohypophysis of the domestic fowl we found immunoassayable Met-enkephalin, but could not detect dynorphin(1-8)-like material. Met-enkephalin immunoreactivity was co-localized with mesotocin in the same nerve endings. Stereospecific opiate binding was specifically located in neurosecretosomes (isolated neurosecretory terminals) of the mesotocin type, as shown by autoradiography. Enkephalins therefore may modulate mesotocin release in an autocrine manner. The neurohypophysis of this common bird appears to be a favorable model for studies of enkephalin function in the absence of dynorphin.

Animals↗

Continuous non-invasive blood pressure monitoring in patients with sleep disorders.

Sleep related breathing disorders are of high prevalence and are often associated with essential hypertension. It is therefore necessary to study blood pressure continuously in all patients with sleep related breathing disorders and arterial hypertension as well as in all patients with essential hypertension and suspected sleep apnoea. To investigate the usefulness of a non-invasive continuous volume-clamp method during sleep we used this technique in parallel with 130 sleep recordings and performed a validation study of the Finapres instrument on a subgroup where continuous invasive blood pressure recordings were available. Absolute pressure values of Finapres are valid when the position and the movement of the sensor were carefully observed and only appropriate segments of the recordings were taken for further evaluation. The high beat to beat resolution of the systolic and diastolic pressure is the main advantage of this non-invasive technique because it reflects rapid blood pressure variations as they occur in sleep related breathing disorders. This could be investigated only invasively until now.

Blood Pressure Determination↗

Insulin stimulates skeletal growth in vivo and in vitro--comparison with growth hormone in rats.

The effect of insulin on skeletal growth was examined by (1) systemic injection, (2) local administration into the tibia growth plate and (3) in vitro by use of chondrocytes in culture. (1) Male rats, body weight 60-75 g, were hypophysectomised. One week after the operation, the animals were divided into three groups. Group A received intraperitoneally saline, group B insulin (5-30 U.kg-1.day-1) and group C human growth hormone (250 micrograms/kg/day) for the following 10 days. In addition, on day 10 the rats were injected with 10 mu-Ci 35-S-sulfate intraperitoneally. Twenty-four h later in the non-fasting state plasma glucose, insulin, somatomedin activity (porcine assay), body weight, nose-rump length, width of the tibia growth plate, and the 35-S-sulfate incorporation into rib cartilage were determined. Compared to saline, growth hormone and insulin treatment significantly enhanced body weights, nose-rump lengths, the widths of the proximal tibia growth plates and the incorporation of sulfate into rib cartilage. For the three skeletal growth parameters, growth hormone was more effective than insulin, while body weights did not differ after insulin or growth hormone treatment. Somatomedin activity (U/ml) was low in group A (0.39 +/- 0.04, n = 9, Mean +/- SEM) and group B (0.34 +/- 0.08, n = 8) and high in the growth hormone treated group C (0.90 +/- 0.09, n = 7; p less than 0.002). (2) To test the possibility that insulin might directly augment skeletal growth, insulin (80 mU) was injected into the proximal tibia growth plate of one leg and saline into the cartilage zone of the other leg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The behaviorally active peptide ACTH 4-10: measurement in plasma and pharmacokinetics in man.

A specific radioimmunoassay for the quantitative measurement of ACTH 4-10 and a procedure for its extraction from plasma have been developed. Its pharmacokinetics was studied in eight healthy male volunteers given ACTH 4-10 125 micrograms/kg body weight as a bolus i.v. injection, by infusion and intranasally. Following the i.v. bolus, plasma levels rapidly declined biexponentially, with half-lives of 0.39 +/- 0.05 min for the alpha-phase and 3.84 +/- 1.5 min for the beta-phase (mean +/- SD). The constant rate i.v. infusion yielded steady-state levels between 0.74 and 5.06 ng/ml plasma. Administered as intranasal spray, absorption of intact ACTH 4-10 was low and variable (maximal bioavailability 7.6%). The results are discussed in relation to the dose-dependent effects of ACTH 4-10 on the auditory evoked potential.

Administration, Intranasal↗

Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin.

Cortisol secretion by the adrenal cortex is thought to depend upon a preceding release of pituitary ACTH. This concept ignores a large number of observations suggesting important extrapituitary influences on adrenocortical function. The present study was designed to demonstrate the contribution of these extrapituitary mechanisms in the release of cortisol induced by human corticotropin releasing hormone (hCRH) in man. In patients with proven deficiency in pituitary ACTH the functional atrophy of the adrenals had been restored by pretreatment with long-acting ACTH. Fifty-eight hours after the second and last injection of ACTH a CRH test was performed (100 micrograms hCRH intravenously). Administration of hCRH induced a small but significant increase in plasma cortisol. Surprisingly, this rise was preceded by an increase in plasma ACTH similar to the ACTH response observed in the control group. It appeared that hCRH is able to stimulate cortisol release in the absence of pituitary ACTH, presumably by stimulating extrapituitary sources of ACTH.

Adenoma↗

Dose-dependent influences on electrophysiological signs of attention in humans after neuropeptide ACTH 4-10.

The afferent humoral system exerts significant influences on brain activity. Central nervous actions of the adrenocorticotropic hormone (ACTH) are most likely to be mediated by information coded in a portion of this hormone structure corresponding to ACTH 4-10. Our previous research suggested an impairing effect of ACTH 4-10 on electrophysiological signs of selective attention in humans. The present experiments in 12 male subjects investigated the influences of ACTH 4-10 on different aspects of attention as indicated by auditory event-related potential (AERP) components. Furthermore, dose-response characteristics of these influences should be examined. Attention performance was tested in a dichotic listening paradigm, after 0, 0.1, 1.0, and 10 mg ACTH 4-10, administered intravenously 1 h prior to testing according to a double-blind latin-square design. Different aspects of attention were measured by brain electrical responses evoked either by frequent standard or rare target tone pips, which the subject had to attend to, or to ignore. The selective type of attention was reflected by the Nd determined as mean difference in amplitude between AERPs to tone pips when attended and when unattended, for a latency range between 0-460 ms post-stimulus. In addition, plasma cortisol, heart rate, blood pressure, and behavioral performance were measured. Results indicated a clear reduction of the Nd amplitude after all doses of ACTH 4-10. Other indicators of attention mechanisms such as mismatch processing were not affected by the peptide. The diminished Nd after ACTH 4-10 was due to an increased processing of unattended stimuli, but simultaneously attended tones were processed less intensively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Influences of ACTH 4-10 on event-related potentials reflecting attention in man.

The present paper is concerned with effects of the 4-10 sequence of the endogenous ACTH on electrophysiological measures of attention in humans. It was attempted to replicate previous findings of an impaired selective attention following administration of an analog of ACTH 4-9. The effect of this analog had been found to dominate in the beginning of the blocks of an attention task, but to fade away with time on task. In the present study, fourteen male students were tested in a dichotic listening paradigm, 40 min after intranasal application of either 0.4 mg ACTH 4-10, or placebo. Averaged auditory evoked potentials (AEPs) to attended and inattended tone pips, EEG power spectra, heart rate and blood pressure, and behavioral performance were measured during task performance. ACTH 4-10 appeared to slightly impair selective attention as indicated by AEP responses. In particular, the positive shift of the AEP waveforms to inattended stimuli was reduced at the beginning of each block of tone pips under ACTH 4-10. The pattern of actions resembled the effects observed after administration of the more potent synthetic analog of ACTH 4-9 in the previous experiment. Effects of ACTH 4-10 on the AEPs to inattended stimuli, however, differed from influences of the synthetic analog in that they did not affect a rather wide latency range but concentrated on the latency range of the P200 component.

Adolescent↗

Further characterization of the extra-arcuate alpha-melanocyte stimulating hormone-like material in hypothalamus: biochemical and anatomical studies.

Previous studies had shown the existence of an extra-arcuate cell group in lateral hypothalamus which contains alpha-melanocyte stimulating hormone (a-MSH)-like immunoreactivity, but no other pro-opiomelanocortin (POMC) immunoreactivity. The question we have attempted to address in this series of studies is whether the material is indeed a-MSH or a cross-reacting material. Chromatographic studies failed to detect any material which is different from a-MSH or des-acetyl-a-MSH, suggesting that either the material is authentic a-MSH/des-acetyl-a-MSH, or that it is not detected by our RIAs. A series of manipulations including dissections of arcuate vs. extra-arcuate hypothalamic areas, treatment with colchicine, lesions with monosodium glutamate and knife cuts were aimed at isolating the extra-arcuate region and showing that it contains an excess of a-MSH over beta-endorphin (B-END), presumably deriving from the extra-arcuate group. However, all studies showed parallel changes in a-MSH and B-END, suggesting that we were not detecting a non-POMC derived a-MSH in these studies. This led to the tentative conclusion that the material was not a-MSH and was not being detected by our RIA's. This hypothesis was tested by further characterizing the material immunohistochemically. These studies led to the conclusion that the extra-arcuate material had a carboxy-terminal homology with a-MSH but differed from it in the midregion, since antisera directed at the 4-10 region of a-MSH failed to stain this non-POMC cell group. Finally, the anatomy of this extra-arcuate group is described, particularly the projections to the striatum, hippocampus, neocortex and olfactory bulb.

Animals↗

Acute effects of desipramine and clomipramine on pituitary-adrenal axis in man.

Brain neurotransmitters play an essential role in central regulation of hypothalamic factors which stimulate or inhibit the secretion of pituitary hormones. Insight in this complex system might be obtained by analysing changes in pituitary and peripheral hormone secretion following the administration of neuroactive drugs which influence the action of neurotransmitters. Desipramine is well-known to inhibit presynaptic norepinephrine reuptake, clomipramine on the other hand interferes with the serotoninergic system. In 15 male volunteers, the effects of single-dose administration of each drug were studied in comparison to placebo. Basal concentrations of ACTH and cortisol, as well as the rise of both hormones following insulin-induced hypoglycemia, were studied. Basal cortisol values and the response to hypoglycemia were not affected by either pharmacon in this study. Slight differences could be seen in the ACTH responses, which were however not significant.

Adrenocorticotropic Hormone↗

ACTH and attention in humans: a review.

In addition to the hormonal action of corticotropin (ACTH) on the adrenal cortex, this peptide and fragments of it may function as chemical signals in CNS synapses. This report reviews studies on behavioral and psychophysiological effects of ACTH-related neuropeptides. Experiments will be emphasized which applied EEG techniques for the measurement of peptide-induced changes on aspects of information processing in man. It is proposed to conceptualize the pattern of actions of ACTH-related neuropeptides as a blocking of suppressive functions occurring, for example, during habituation or selective attention. Disinhibitory effects mediated by structures of the limbic system may be responsible for repeatedly observed improvements of sustained attention, but impairments of selective attention following the administration of ACTH-related neuropeptides. Under the influence of these peptides the attention is more easily attracted by stimuli, irrespective of their relevance.

Adrenocorticotropic Hormone↗

Relationships between sleep stages and plasma cortisol: a single case study.

The relationship between the plasma cortisol level and sleep stages was investigated in a single male subject across 17 nights. Blood samples were taken every 30 min from 11.00 p.m. until 02.30 a.m. and every 15 min during the rest of the night. Data analyses performed for the whole nights did not give evidence for strong relations between plasma cortisol and sleep stages. Analyses on data of the second part of the night, beginning with the onset of the first cortisol peak, revealed that plasma cortisol was primarily decreasing when rapid eye movement sleep (REM) was present. Sleep stage I and periods of wakefulness were associated with increasing cortisol levels. There was no evidence for a particular EEG event triggering the first rise of plasma cortisol during the night.

Adult↗