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Biomedical subjects

R Ekman

Publications and source records attributed to R Ekman.

At least 163 records · Page 9Linked to original sources

Electroconvulsive shocks increase the concentration of neocortical and hippocampal neuropeptide Y (NPY)-like immunoreactivity in the rat.

Studies on humans and rats have suggested that neuropeptide Y (NPY) is involved in major depression and anxiety. Therefore, we conducted the present study in order to elucidate the effect of repeated (13 or 14 days) treatment of rats with electroconvulsive shocks (ECS) on the concentration of NPY-like immunoreactivity (-LI) in various brain regions, adrenals and plasma. In addition, the effect of ECS on 125I-NPY binding was studied in 3 brain regions. The effects of ECS were compared to effects of 3 control treatments: one group not being handled at all during the time period, one group handled like the ECS-group but not receiving shocks, and one group receiving shocks below the threshold for induction of convulsions. The latter group developed behavioral signs reminiscent of the inescapable shock-induced 'learned helplessness' syndrome (a proposed animal model of depression). We found that the concentration of NPY-LI in the frontal and parietal cortex and in the hippocampus were approximately doubled in the ECS-group as compared to the 3 control groups. No changes in NPY-LI were detected in the striatum, hypothalamus, pons, olfactory bulbs or cerebellum, nor in plasma or adrenals. In spite of the marked changes in NPY-LI concentration, the binding characteristics of 125I-NPY in the frontal and parietal cortex and in the hippocampus were similar in all 4 groups of rats. Finally, we confirmed the previous observation that ECS increase [3H]prazosin binding in cortex. In conclusion, ECS treatment increases neocortical and hippocampal NPY-LI concentrations, while leaving 125I-NPY binding unaffected. Subconvulsive shocks were without effect.

Animals↗

Vasoactive peptide release in the extracerebral circulation of humans during migraine headache.

The innervation of the cranial vessels by the trigeminal nerve, the trigeminovascular system, has recently been the subject of study in view of its possible role in the mediation of some aspects of migraine. Since stimulation of the trigeminal ganglion in humans leads to facial pain and flushing and associated release of powerful neuropeptide vasodilator substances, their local release into the extracerebral circulation of humans was determined in patients who had either common or classic migraine. Venous blood was sampled from both the external jugular and cubital fossa ipsilateral to the side of headache. Plasma levels of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide were determined using sensitive radioimmunoassays for each peptide, and values for the cubital fossa and external jugular and a control population were compared. A substantial elevation of the calcitonin gene-related peptide level in the external jugular but not the cubital fossa blood was seen in both classic and common migraine. The increase seen in classic migraine was greater than that seen with common migraine. The other peptides measured were unaltered. This finding may have importance in the pathophysiology of migraine.

Adult↗

Neuropeptide levels in Alzheimer's disease and dementia with frontotemporal degeneration.

The CSF levels of somatostatin-LI (SLI), neuropeptide Y (NPY-LI) and Delta Sleep Inducing Peptide (DSIP-LI) have been measured in patients with dementia of Alzheimer type (DAT) and dementia with frontotemporal degeneration of non-Alzheimer type (FTD). The distribution pattern of cortical degeneration differs between these two types of dementia. DAT shows degeneration of mainly temporo-parietal and temporo-limbic structures, whereas FTD discloses its main degeneration in the frontotemporal regions (Brun, 1987). The somatostatin-LI was significantly reduced both in DAT and FTD. NPY-LI showed a significant reduction in DAT but not in FTD. A tendency to a reduction with duration of the disease was observed in DAT whereas the contrary was noted in FTD. The DSIP-LI levels were reduced in DAT and slightly increased in FTD. The study provides an evidence of neurochemical differences between the two primary degenerative dementias.

Adult↗

Intestinal endocrine cells in Hirschsprung's disease. No reduction in density in aganglionic compared with ganglionic segment.

The aganglionic intestine in Hirschsprung's disease displays a severe neuronal derangement. The changes are particularly evident in the muscular innervation. In the gut the endocrine cells are among the cells known to be influenced by neurons. We have, therefore, examined the endocrine cells in ganglionic and aganglionic intestine using immunocytochemistry and immunochemistry. The endocrine cells were studied using antibodies against the neuroendocrine marker chromogranin A, the amine serotonin and the hormonal peptides somatostatin, glucagon/glicentin and peptide YY (PYY), thus covering virtually all endocrine cell types known to occur in this region. The PYY concentration in the mucosal layer was measured by radioimmunoassay. In ganglionic as well as in aganglionic intestine large populations of cells storing chromogranin A, serotonin, glucagon and PYY and a smaller population of somatostatin cells were seen. There was an increase in the density of these cells in the aganglionic intestine compared with ganglionic. The data indicate that the endocrine cell populations in the intestinal wall can be maintained despite severe derangements of the nerve supply.

Cell Count↗

PYY-like material and its spatial relationship with NPY, CGRP and 5-HT in the lung of the Syrian golden hamster.

We investigated the presence of peptide YY, neuropeptide Y, calcitonin gene-related peptide and serotonin in the hamster lung by radioimmunoassay, high performance liquid chromatography and immunocytochemistry. Lung-tissue concentrations of peptide YY and neuropeptide Y were 1.3 +/- 0.2 and 2.5 +/- 0.2 pmol/g wet weight, respectively. These two closely related pancreatic peptides were demonstrated in separate peaks with high performance liquid chromatography. The peptide YY appeared fragmented as immunoreactive peptide YY eluted primarily late in the gradient but showed additional peaks early in the gradient. Peptide YY-like immunoreactivity (PYY-LI) was predominantly observed in one or more cells of neuroepithelial bodies in all airways peripheral to bronchioles, and in solitary neuroendocrine cells primarily located in the same peripheral areas. Neuropeptide Y-LI was seen in individual, thin nerve fibers around arteries and veins, in the airway lamina propria, and in the airway epithelium; in the latter also immunopositive nerve terminals were located. This pattern did not appear to coincide with that of calcitonin gene-related peptide-LI in epithelial nerve fibers and terminals. Peptide YY-LI, calcitonin gene-related-LI and serotonin-LI were present in cells of one and the same neuroepithelial body. However, peptide YY-LI was never found to be co-localized with calcitonin gene-related-LI or serotonin-LI, but the latter two were co-localized as previously reported.

Animals↗

Changes in the levels of neuropeptide Y-LI in the external jugular vein in connection with vasoconstriction following subarachnoid haemorrhage in man. Involvement of sympathetic neuropeptide Y in cerebral vasospasm.

NPY is a putative neurotransmitter mainly co-localized with noradrenaline in sympathetic fibers which innervate the cerebral vasculature. The origin of most of the perivascular NPY fibers seems to be in the superior cervical ganglion. To investigate involvement of Neuropeptide Y (NPY) mechanisms in subarachnoid haemorrhage (SAH), twenty patients with SAH were investigated. NPY-LI (-like immunoreactivity) levels in the external jugular vein were assessed using radioimmunoassay in blood samples collected post-operatively (or after SAH in non-surgical patients) on days 1,2,3, 5,7 and 9. These levels were compared with the clinical course and blood flow velocity changes monitored with ultrasonic Doppler equipment from both middle cerebral arteries (MCA) and both internal carotid arteries (ICA). Compared to NPY-LI levels in 14 controls (mean 116 +/- 3 pmol/1), increased levels (up to 253 pmol/l) and a close relationship between velocities and NPY-LI levels were found in a subpopulation of the SAH patients. When comparing the mean haemodynamic index (V MCA/ipsilateral V ICA) and mean NPY-LI levels in each of the 20 patients, a correlation of r = 0.75, p = 0.0001 was found. Increased NPY-LI were found (131 +/- 8 pmol/l) when simultaneous Doppler velocity recordings showed vasoconstriction (Haemodynamic index greater than 5) compared with samples taken when the haemodynamic index was less than 5, p less than 0.05. When MCA velocity exceeded 120 cm/sec. increased levels were found (129 +/- 9 pmol/l) compared with the conditions when MCA velocity was less than 120 cm/sec (113 +/- 5 pmol/l), p = 0.06. The results indicate a possible NPY involvement in cerebral vasoconstriction after SAH.

Adult↗

Atrial natriuretic peptide-LI following subarachnoid haemorrhage in man.

Atrial natriuretic peptide-like immunoreactivity (ANP-LI) was measured in plasma from the external jugular vein (EJV) in the postoperative course of 11 patients with aneurysmal subarachnoid haemorrhage. Samples were taken on day, 1, 2, 3, 5, 7 and 9 after operation and ANP-LI levels were determined using radioimmunoassay. Ten healthy volunteers were investigated with one EJV plasma sample. Comparing the whole group of SAH patients with the control group, no significant differences in ANP-LI levels were found. In one patient very high ANP-LI levels were found together with high mean plasma sodium levels and high urine sodium excretion. This suggests that there is no general correlation between plasma ANP-LI and SAH; in occasional patients such a correlation may be secondary to changes in plasma sodium levels.

Adult↗

Dose- and time-response effects of pantethine on open-field behavior, and on central neurotransmission in rats.

In this study the dose- and time-related effects of pantethine on open-field behavior and central neurotransmissions were investigated in rats. Pantethine administered in low doses (0.48-0.96 mM/kg SC) only marginally influenced the activity of the animals, but induced a significant decrease of hypothalamic noradrenaline level without influencing the concentrations of dopamine and DOPAC. Injected in higher doses (1.95-3.90 mM/kg SC), the compound produced a marked depression of both open-field activity and noradrenaline levels, but increased the concentrations of dopamine and DOPAC in the hypothalamus. Twelve hr after the administration of the substance, its effect was attenuated, and 24 hr after the treatment neither the behavioral nor the monoamine parameters differed significantly from the control values. Concerning the somatostatin, pantethine administered in high doses (1.95-3.90 mM/kg SC) decreased the striatal concentration of somatostatin 4 hr after the injection, and this effect was attenuated 24 hr after the treatment. These data suggest that the pantethine-induced behavioral changes are correlated with its effect on central catecholaminergic and somatostatinergic transmission.

3,4-Dihydroxyphenylacetic Acid↗

Distribution of peptidergic nerves in the choroid plexus, focusing on coexistence of neuropeptide Y, vasoactive intestinal polypeptide and peptide histidine isoleucine.

Choroid plexus from rat, guinea-pig, rabbit and pig was investigated by light-microscopic immunohistochemistry and by radioimmunoassay for the presence of neuropeptides. A moderately dense supply of nerve fibers containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), respectively, was found around blood vessels and in close relation to the secretory epithelium in both pig and rabbit, while lower densities of nerve fibers were found in rat and guinea-pig. Peptide concentrations ranged from 10-40 pmolequivalents/g (pmoleqv/g) for NPY and 0.5-6 pmoleqv/g for VIP in all four species. Peptide histidine isoleucine (PHI) immunoreactive nerve fibers were present in pig choroid plexus at a lower density than NPY and VIP but with a similar distribution. Low concentrations of substance P (0.3-3 pmoleqv/g) and calcitonin gene-related peptide (0.1-3 pmoleqv/g) were found to a varying degree in choroid plexus tissue from the different species, while immunohistochemical investigation was unable to detect any immunoreactive nerve fibers. NPY was often found to coexist with VIP and PHI in pig choroid plexus, while a lesser amount of nerve fibers showed coexistence of NPY and the noradrenaline synthetizing enzyme, dopamine-beta-hydroxylase. Surgical sympathetic denervation by excision of the superior cervical ganglion in the rabbit abolished NPY-containing nerve fibers, as revealed by immunohistochemistry, but only decreased NPY levels by one third, which may be due to different identity of the peptide being detected by the two techniques. It is concluded that NPY-containing nerve fibers have a dual origin in the choroid plexus and coexist with either noradrenaline or VIP/PHI.

Animals↗

Peptide YY-like immunoreactivity in sympathetic neurons of the rat.

The occurrence of peptide YY-like peptides in parts of the sympathetic nervous system of the rat was studied by immunocytochemistry and immunochemistry plus analysis by high performance liquid chromatography. Peptide YY-immunoreactive neurons and nerve fibers were detected in the superior cervical ganglion. Co-localization studies indicated that peptide YY and neuropeptide Y immunoreactivities co-exist in a subpopulation of neurons of the superior cervical ganglion. Immunochemical analysis revealed peptide YY-immunoreactive material, distinct from neuropeptide Y, in extracts of the superior cervical ganglion. On reverse-phase high performance liquid chromatography, extracts of superior cervical ganglion revealed several peaks of peptide YY-like immunoreactive material, one of which eluted close to the position of authentic porcine peptide YY. Peptide YY-immunoreactive nerve fibers were also present in sympathetic target tissues including the auricula and atria of the heart, carotid body, submandibular salivary gland and the adrenal cortex. It is suggested that peptide YY and/or peptide YY-like peptides are present not only in endocrine cells, but also in a subpopulation of cell bodies and fibers of the peripheral sympathetic nervous system.

Animals↗

Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in multiple sclerosis.

The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.

Adult↗

Road traffic accidents in a Swedish municipality.

A continuous all embracing registration of acute, in-patient and out-patient visits at hospitals and primary health care centres, was conducted in Skaraborg County in western Sweden. A special focus was directed at accident cases which account for 20% of the total number of acute visits. The accidents were divided up by environment: home, work, traffic and other. Cases of road traffic accidents have been mapped out in more detail with the help of standardised and structured surveys via telephone interviews, information from hospital records, and death certificates. This study aimed at achieving an increased understanding and knowledge about the accident pattern in the traffic environment in a municipality. Road traffic accidents accounted for 6.5% of all accidents. Cyclists, car drivers, car passengers and pedestrians were the most common victims. Children showed a high frequency of bicycle accidents. There was an increased risk of injury for young car-drivers. Thirty-six per cent were single-accidents. Cars and bicycles dominated among injury-inducing vehicles. Head, arm and knee injuries were most common. Twenty-six per cent of the victims were hospitalized. Safety devices were not used in 10% of cases where they should have been used according to legislation. A comparison of our registration system for road traffic accidents with the official statistics of Sweden reveals a substantial under-reporting of road traffic accidents in the latter. Consequently, a need exists for the surveillance of injuries by the public health services as a basis of injury control.

Accidents, Traffic↗

Involvement of perivascular sensory fibers in the pathophysiology of cerebral vasospasm following subarachnoid hemorrhage.

The involvement of perivascular sensory fibers containing substance P (SP) and calcitonin gene-related peptide (CGRP) in the events occurring in conjunction with subarachnoid hemorrhage (SAH) has been studied in a rat model. Two days after blood injection, the time point at which maximum vasoconstriction is occurring in this model, immunocytochemistry and radioimmunoassay showed a reduction in SP- and CGRP-like immunoreactivity (LI). The quantitative measurements revealed a significant 50% reduction of CGRP-LI and a slight reduction of SP-LI in SAH as compared to controls. This partial reduction in neurotransmitter content (denervation) caused no change in the sensitivity of the rat basilar artery to SP or CGRP as studied using a sensitive in vitro method. However, the maximum relaxant response to CGRP was increased from 52 to 81% (p less than 0.05), while there was no change in the maximum SP-induced relaxations. It is suggested that not only a pre-, but also a postsynaptic modulation of perivascular sensory fibers may occur in experimental SAH.

Animals↗

Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres.

In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal peptide-LI (VIP-LI), substance P-LI (SP-LI) and calcitonin generated peptide-LI (CGRP-LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY-LI and SP-LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY-LI and SP-LI were significantly increased. CGRP-LI was not altered, despite the fact that this peptide co-exists in many tissues with SP. There was no change in VIP-LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP-LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho-adrenal system.

Afferent Pathways↗

Gamma 2-MSH in congestive heart failure: relation to atrial natriuretic peptide, arginine vasopressin and catecholamines.

A possible role of the proopiomelanocortin derived peptide gamma 2-melanocyte stimulating hormone (gamma 2-MSH) has been studied in patients with various degrees of congestive heart failure (CHF). The profile of changes in circulating levels of gamma 2-MSH-like immunoreactivity (-LI) has been compared with those of atrial natriuretic peptide (ANP)-LI, arginine vasopressin (AVP)-LI and catecholamines in CHF. Patients with moderate CHF (New York Heart Association stages I-II) showed significantly higher levels of h-alpha ANP-LI and NA (P less than 0.05) compared to controls. Patients with severe CHF (stages III-IV) had significantly higher levels of all hormones measured compared to controls: noradrenaline, P less than 0.001; adrenaline, P less than 0.001; gamma 2-MSH-LI, P less than 0.001; h-alpha ANP-LI, P less than 0.05; AVP-LI, P less than 0.01. For the catecholamines and gamma 2-MSH-LI there was a significant increase from moderate to severe forms of CHF. A significant correlation was observed between gamma 2-MSH-LI and noradrenaline, and between h-alpha ANP-LI and noradrenaline in patients with CHF. The present results show that gamma 2-MSH-LI is increased only in severe forms of cardiac failure, and that this change is more closely related to the increase in circulating levels of noradrenaline than to increased levels of ANP-LI or AVP-LI.

Aged↗

Gamma 2-MSH increases during graded exercise in healthy subjects: comparison with plasma catecholamines, neuropeptides, aldosterone and renin activity.

To evaluate the possibility that the proopiomelanocortin (POMC)-derived peptide gamma 2-melanocyte stimulating hormone (gamma 2-MSH) has a role in circulatory regulation in man we studied circulating levels of this peptide at three different stages of physical activity in 10 young healthy subjects. The results were compared to simultaneously measured plasma levels of catecholamines, neuropeptide Y, vasopressin, renin activity, aldosterone and human alpha-atrial natriuretic peptide (alpha-hANP) and of the vasodilatory peptides calcitonin gene-related peptide, substance P and vasoactive intestinal peptide. The plasma levels of gamma 2-MSH-LI (like immunoreactivity) increased from 1009 +/- 101 pmol l-1 at supine rest to 1281 +/- 79 pmol l-1 when measured after 10 min walking (P less than 0.05), and remained at this increased level also after a consecutive further increase of physical activity (4 min stair rush), 1293 +/- 87 pmol l-1 (P less than 0.05 vs. at rest). The increase in circulating gamma 2-MSH-LI levels preceded the elevation of the venous plasma noradrenaline level, but did not rise further with more pronounced activation of the sympathetic nervous system at the highest grade of physical activity examined.

Aldosterone↗

Corticotropin, cortisol and beta-endorphin responses to the human corticotropin-releasing hormone during melancholia and after unilateral electroconvulsive therapy.

Previous research in neuroendocrinology has evidenced that hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) depends on hypersecretion of corticotropin-releasing hormone (CRH). The aim of this study was to investigate the activity of HPA before and after recovery in depressed patients treated with electroconvulsive therapy (ECT). An h-CRH-stimulation test was performed on 2 occasions with examination of the HPA axis before ECT treatment during episodes of major depressive disorders with melancholia, and during the recovery phase after treatment. The results showed that patients during depression had significantly higher plasma levels of cortisol at 15 and 30 min after h-CRH-administration than after recovery. Depressed patients had significantly higher plasma levels of beta-endorphin 30 min after h-CRH-stimulation. The results are in agreement with previous studies, which have shown hypercortisolemia during depression. A possible hypersecretion of CRH may explain the effect on cortisol and beta-endorphin. No significant differences were found between cumulative responses of corticotropin, cortisol and beta-endorphin, calculated as the areas under the concentration curves.

Adrenocorticotropic Hormone↗

Motilin and infantile colic. A prospective study.

Two hundred and nineteen infants, consecutively born, took part in a prospective study of infantile colic from birth to 12 weeks of age. The prevalence of infantile colic in this group was 17.4%. S-motilin was studied in 78 term infants (19 with and 59 without infantile colic) at birth (cord blood), at one day, and at 6 and 12 weeks of age, respectively. Basal motilin levels were raised both in cord blood (p less than 0.01) and in blood from neonates (p less than 0.001) who developed colic as well as in 6 week (p less than 0.05) and in 12-week-old infants with colic (p less than 0.01). Formula-fed infants with colic had higher basal motilin levels than formula-fed controls at 6 and 12 weeks of age (p less than 0.05). Breast-fed infants with colic had higher basal motilin levels than breast-fed controls at 12 weeks of age (p less than 0.05). The raised levels of motilin from the first day of life in infants who develop infantile colic might indicate that the gastrointestinal tract is affected in infants with infantile colic, before any symptoms of colic appear.

Colic↗