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Biomedical subjects

R Ekman

Publications and source records attributed to R Ekman.

At least 109 records · Page 6Linked to original sources
PubMed1994

Corticotropin-releasing factor and neuropeptide Y: role in emotional integration.

The amygdala complex integrates stressful stimuli and is critical in transducing their aversive value into autonomic, endocrine and behavioural responses. Stimulation within the amygdala complex produces signs of fear without a relevant external object, while lesions in this region abolish normal fear responses. In a manner characteristic of phylogenetically old limbic brain areas, the complex neurochemical anatomy of the amygdala involves a large number of phylogenetically old peptide mediators. The distribution and connectivity of these peptide systems have been extensively studied, but less is known about their functional role. Recent evidence suggests that two neuropeptides, corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) exert a reciprocal regulation of responsiveness to stressful stimuli, possibly via an interaction of these two systems in the amygdala.

Amino Acid Sequence↗
PubMed1994

Absence of vasoactive peptide release from brain to cerebral circulation during onset of migraine with aura.

In eight patients carotid angiography was required for evaluation of transient neurological attacks. Cerebral blood flow results, angiography and clinical observations subsequently suggested the diagnosis of migraine. We measured plasma concentrations of substance P(SP), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in repeated blood samples obtained from the carotid artery and the internal jugular vein in conjunction with cerebral angiography followed by 4 to 6 repeated recordings of regional cerebral blood flow (rCBF) with the intracarotid Xenon-133 injection technique. This technique is known to induce attacks of migraine with aura in many sufferers. Four patients developed aura symptoms. In three this was succeeded by throbbing headache. Typical, migraine-related, focal hypoperfusion occurred in conjunction with the aura symptoms. The remaining four patients had no symptoms or rCBF changes. There were no systematic or statistically significant changes over time in arterial-venous plasma concentrations or in the release rates of any of the peptides. All migraineurs had an overall elevated mean CGRP value compared to control values from the literature. The overall plasma levels of the potent vasoconstrictor NPY were higher (p < 0.10) in the group that developed symptoms and rCBF changes (136 pmol/l) than in the non-symptomatic group (97 pmol/l). The difference in NPY levels could perhaps be associated with the focal rCBF decrease seen in the attack group.

Adult↗
PubMed1994

Pancreatic peptide YY in alloxan diabetic mice.

Peptide YY (PYY) immunoreactive material was detected in the splenic and duodenal portions of the adult mouse pancreas, using immunocytochemical and immunochemical methods. Cells displaying PYY immunoreactivity generally occurred at the islet periphery. Double immunostaining enabled localization of PYY to a major subpopulation of the glucagon cells and to subpopulations of the pancreatic polypeptide (PP) cells and the somatostatin cells. In contrast, no PYY immunoreactivity occurred in the insulin cells. In alloxan-treated hyperglycemic mice, PYY immunoreactive cells were increased in number and distributed throughout the islets, in parallel with the glucagon, PP, and somatostatin cells. Analysis by radioimmunoassay indicated a significant increase in the concentration of pancreatic PYY after alloxan treatment in the splenic portion of the pancreas, but not in the duodenal portion. Pancreatic glucagon concentrations were not significantly changed. It is concluded that the islet content of PYY increases in alloxan diabetes, which might contribute to the accompanying alterations in islet function.

Alloxan↗
PubMed1994

Magnesium sulphate infusion decreases circulating calcitonin gene-related peptide (CGRP) in women with primary Raynaud's phenomenon.

The effects of two different vasodilating agents (MgSO4 infusion and the calcium antagonist nifedipine) on circulating levels of calcitonin gene-related peptide (CGRP) were studied in 12 women with pronounced primary Raynaud's phenomenon (PRP) and in 12 healthy females. There were no significant differences with regard to basal levels of circulating CGRP between women with PRP and the control group; median 15.5 (range 10-48) vs. 14 (range 10-69) pmol l-1, respectively. However, treatment with MgSO4 infusion significantly decreased circulating CGRP in women with PRP only from median 15.5 (range 10-48) to 10 (range 10-110) pmol l-1) (P < 0.05). On the other hand 14 days of treatment with nifedipine did not affect circulating CGRP in either of the investigated groups. Erythrocyte magnesium (ery-Mg) levels increased significantly after MgSO4 infusion in women with PRP (2.43 +/- 0.13 vs. 2.52 +/- 0.15 mmol l-1, P < 0.05) but not in the controls (2.51 +/- 0.24 vs. 2.57 +/- 0.28 mmol l-1, ns). In conclusion, the decrease of circulating CGRP after MgSO4 infusion in women with PRP provides further evidence that magnesium plays a significant role in the pathophysiology of PRP.

Adult↗
PubMed1994

Developmental studies on vasoactive intestinal peptide, substance P and calcitonin gene-related peptide in salivary glands of postnatal rats.

The development of vasoactive intestinal peptide, substance P and calcitonin gene-related peptide in parotid, submandibular and sublingual glands of the male rat was followed by immunochemistry and immunocytochemistry. The total amounts of these peptides increased in surges during the first 8 weeks of the animal's life; one within 2-4 weeks and the other beginning 1-2 weeks later. Nerve fibres containing these peptides were present at birth showing a pattern of distribution similar to that in adults. During the first 4 weeks the nerve fibres increased in number.

Animals↗
PubMed1994

Dynamic training and circulating neuropeptides in patients with rheumatoid arthritis: a comparative study with healthy subjects.

This study aimed at evaluating the effects of a dynamic physical training programme on circulating levels of corticotropin-releasing hormone (CRH), beta-lipotropin (beta-LPH), and beta-endorphin (beta-EP) after high-intensity training for 6 weeks (60 min twice a week) and after low-intensity training (home-training) for another 6 months in patients with rheumatoid arthritis (RA) and in healthy subjects. Additionally, differences in neuropeptide levels between the two groups were studied. A total of 30 patients with RA were randomly allocated to the study, 15 in the training group (TG) and 15 in the control group (CG). In addition, 20 healthy subjects (10 in TG; 10 in CG) participated. In addition to the biochemical analyses, the following variables were assessed for the RA group: pain and disability (Stanford health assessment questionnaire), joint tenderness (Ritchie articular index), disease activity, muscle function, aerobic capacity, sociodemographic data and attitudes. The results obtained at the start revealed significant differences (p < 0.05) between RA patients and healthy subjects concerning CRH levels, RA patients showing the lower levels (RA-group Md = 24 pmol/L, healthy group Md = 29 pmol/L). No significant differences concerning beta-LPH and beta-EP were found here. After the high-intensity training period, a significant increase of the CRH levels were found for the RA-TG (pretest Md = 24 pmol/L, after 6 weeks Md = 27 pmol/L, p < 0.05). No such results were found for the healthy-TG or the control groups. Concerning beta-EP, significant differences between the RA-TG and healthy-TG were found after the training. RA patients generally showing higher levels as compared with the healthy (RA-group Md = 42 pmol/L, healthy group Md = 36 pmol/L, p < 0.05). The same pattern was found for the beta-LPH levels. In conclusion, the effects of physical training on circulating neuropeptides remain still incompletely examined, and there is no definite answer to the question whether increased beta-EP levels are good or bad.

Adult↗
PubMed1994

Changes in plasma levels of vasoactive substances during routine acetate and bicarbonate hemodialysis.

Hemodynamic stability is better preserved during bicarbonate hemodialysis compared to acetate. We have studied the effects of bicarbonate (HDB) and acetate hemodialysis (HDA) on plasma levels of vasoactive substances. The treatments were performed for 270 min. A cuprophan plate dialyzer was used. The ultrafiltration volume and the ultrafiltration rate were identical in the individual patients during the two treatments. In the case of vasoconstrictors there was an increase in neuropeptide Y (NPY) (20%, p < 0.01) during HDB and arginine vasopressin (AVP) was unchanged. Unlike this was the response during HDA when there was no change in NPY and a decrease in AVP (38%, p < 0.01). An increase in noradrenaline (NA) (41%, p < 0.05) occurred during HDA different from what was the case during HDB. There was a gradual increase in renin (PRA) during both HDB (141%, p < 0.05) and HDA (148%, p < 0.01). With respect to vasodilators there were no differences between the two regimes regarding calcitonin gene-related peptide (CGRP) and motilin (MOT). The change in substance P (SP) during the treatments was also similar but somewhat more pronounced during HDB. Thus, an initial rise occurred (HDB, 81%, p < 0.01; HDA, 36%, p < 0.05) followed by a decrease (HDB, 26%, p < 0.05) or a tendency to decrease (HDA, 12%, p = 0.058) during the remaining part of the treatment. A rise in beta-endorphin (beta-END) occurred during HDB (10%, p < 0.05) but not during HDA. An increase in vasoactive intestinal peptide (VIP) occurred during HDB (27%, p < 0.05) different from the decrease during HDA (11%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1993

Antihistone and anti-dsDNA autoantibodies in Alzheimer's disease and vascular dementia.

In order to evaluate their prevalence in senile dementias, serum titer of antibodies against histones and double stranded deoxyribonucleic acid (dsDNA) were measured by means of the ELISA test in patients suffering from vascular dementia (VD), presenile Alzheimer's disease (AD), and senile dementia of the Alzheimer's type (SDAT). Only three subjects out of 87 had dsDNA autoantibodies. On the contrary, VD and SDAT showed high titers of antibodies against histones when compared to healthy controls. A significant relationship was also found between antihistone serum titer and degree of dementia in AD. Results were not influenced by gender, age, or duration of illness. Presence of antihistone antibodies in dementias might reflect an alteration of membrane fluidity and integrity with leakage of nuclear immunogens or disturbances of immune functions, as frequently observed in dementia disorders.

Aged↗
PubMed1993

Demonstration of immunoglobulin G with affinity for dopamine in cerebrospinal fluid from psychotic patients.

Using an enzyme-linked immunosorbent assay, significantly raised concentrations of immunoglobulin G with affinity for the neurotransmitter dopamine were demonstrated in cerebrospinal fluid from psychotic patients. We have varied the antigen presentation in order to find a conjugate with low unspecific binding. The conjugation of dopamine to carbodiimide-activated poly-L-glutamic acid and that to activated succinimide ester of biotin are described. The use of glutaraldehyde conjugation is not recommended because of the risk of formation of tetrahydroisoquinolines. A strong correlation (r = 0.94, P < 0.001) between the results obtained with dopamine conjugated to poly-L-glutamic acid and dopamine conjugated to biotin was observed. Forty-two human cerebrospinal fluid samples from 20 psychotic patients, (12 with a bipolar disorder and 8 with schizophrenia) and 22 control patients, with various neurological diseases but no apparent psychiatric diseases were investigated. A significantly higher incidence (P < 0.001) of antibodies with affinity for dopamine were found in the group of psychotic patients compared with the neurological control group.

Adolescent↗
PubMed1993

Peptide YY in the mammalian pancreas: immunocytochemical localization and immunochemical characterization.

Peptide YY (PYY) was demonstrated by immunochemical and/or immunocytochemical methods in endocrine cells in the pancreas of adult mice, rats, guinea-pigs, cats, dogs, pigs and cows. In the pancreas of mouse and rat, immunoreactive PYY was observed in a major subpopulation of the glucagon cells (splenic lobe of the pancreas); immunoreactive PYY also occurred in a subpopulation of the pancreatic polypeptide (PP) cells (duodenal lobe), and in a few extra-insular endocrine cells dispersed throughout the pancreatic parenchyma. In the pancreas of cat, dog and pig immunoreactive PYY was found to coexist with PP, but not with glucagon. Radioimmunoassay (RIA) revealed PYY-like material in extracts of pancreas (and colon) of all the species examined. The highest concentrations were found in the pancreas of cat and mouse; moderate amounts were found in the rat and only small amounts were detected in guinea-pig and pig. The concentrations in the pancreas were uniformly much lower than those in the colon. Analysis by high performance liquid chromatography (HPLC) showed that the PYY-immunoreactive material from pancreas (and rat colon) had an elution profile very similar to that of synthetic PYY, and distinct from that of PP and neuropeptide Y.

Amino Acid Sequence↗
PubMed1993

Gastrointestinal regulatory peptides in systemic sclerosis.

OBJECTIVE: Gastrointestinal involvement commonly occurs in systemic sclerosis (SSc), but its pathogenesis is not well understood. Since there is evidence of a defect in neurotransmitter release, we were interested in examining the relationship between gastrointestinal dysfunction and plasma concentrations of gastrointestinal regulatory peptides in patients with SSc. We studied 43 consecutive patients, 18 with diffuse and 25 with limited cutaneous disease. METHODS: Levels of corticotropin-releasing hormone (CRH), gastrin, motilin, neuropeptide Y (NPY), and peptide YY (PYY) were determined by radioimmunoassay and high-performance liquid chromatography (HPLC). RESULTS: Plasma concentrations of CRH, motilin, NPY, and PYY were significantly increased among SSc patients compared with healthy control subjects, and HPLC-characterization of motilin, NPY, and PYY showed a different pattern of fragments. No correlation was found between esophageal hypomotility and the concentration of peptide. Acid output did not correlate with gastrin levels, but was more often increased in patients with increased CRH and NPY values. Fat malabsorption, assessed by the triolein breath test, was more common among patients with increased motilin and PYY. CONCLUSION: This study shows that elevated peptide concentrations commonly occur in patients with SSc. Since regulatory peptides are involved in gastrointestinal motility, secretion, and absorption, further characterization of this neuroendocrine system may help in understanding the complex regulation of gastrointestinal dysfunction in SSc.

Adult↗
PubMed1993

Biosynthesis of corticotropin-releasing hormone in human T-lymphocytes.

Corticotropin-releasing hormone (CRH) is a 41-amino acid neuropeptide which increases the transcription of the proopiomelanocortin (POMC) gene, as well as the biosynthesis and secretion of POMC-derived peptides. Using a specific human CRH radioimmunoassay we have shown that human T-lymphocytes contain immunoreactive CRH. We studied the effects of phytohemagglutinin (PHA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) on the biosynthesis of CRH in human T-lymphocyte cell cultures. A significant increase in CRH mRNA levels was observed in human lymphocytes after 12 h of PHA/TPA treatment, while the levels decreased after 22 h. These findings could imply an immunomodulatory role for CRH that could be due to autocrine and/or paracrine interactions.

Cells, Cultured↗
PubMed1993

Peptide YY: a neuropeptide in the gut. Immunocytochemical and immunochemical evidence.

Peptide YY immunoreactivity was detected in neuronal elements in the upper digestive tract of the rat, cat, ferret and pig by immunocytochemistry and radioimmunoassay combined with high-performance liquid chromatography. The two peptide YY antisera used do not recognize the related peptides neuropeptide Y and pancreatic polypeptide. In the rat peptide YY-immunoreactive nerve fibres were virtually restricted to the stomach smooth muscle of the minor curvature where they were numerous. Peptide YY-immunoreactive nerve cell bodies occurred in small ganglia on the serosal surface of the minor curvature. In the cat and ferret peptide YY-immunoreactive nerve fibres occurred in the circular smooth muscle layer of both the minor and major curvatures of the stomach and also in the upper small intestine; such fibres were numerous also in myenteric ganglia in these regions. In the pig, they were few but had roughly the same distribution as in the cat and ferret, except that they were quite numerous in thick muscle bundles close to the oesophagogastric junction. The presence of peptide YY-immunoreactive nerve cell bodies within the myenteric ganglia along the upper digestive tract of cat, ferret and pig, and in serosal ganglia of the rat stomach, indicates that at least some of the peptide YY-immunoreactive fibres demonstrated originate in or close to the gut wall. Double-staining experiments revealed that virtually all peptide YY-containing neurons and nerve fibres were distinct from those storing neuropeptide Y. Peptide YY-immunoreactive endocrine cells were encountered not only in the lower intestines but also in the stomach of the four species studied. In the antrum such cells were numerous and constituted a subpopulation of the gastrin-containing cells. In the oxyntic mucosa they were few and contained somatostatin. Radioimmunoassay revealed peptide YY-like peptides in gastric mucosa and smooth muscle from the upper digestive tract of all four species examined. The results of high-performance liquid chromatography suggest that the peptide YY-like material in the upper digestive tract is distinct from neuropeptide Y and pancreatic polypeptide and identical with authentic peptide YY except in the antral mucosa where only a small proportion of the peptide YY-immunoreactive material eluted like authentic peptide YY.

Animals↗
PubMed1993

Cortical spreading depression does not result in the release of calcitonin gene-related peptide into the external jugular vein of the cat: relevance to human migraine.

There is circumstantial evidence that cortical spreading depression (SD) may account for the scotoma and the "spreading cortical oligemia" seen during migraine with aura. It has been shown that calcitonin gene-related peptide (CGRP) is increased in blood taken from the external jugular vein (EJV) in humans during migraine and after stimulation of the trigeminal ganglion. To test the hypothesis that cortical SD may elevate the concentration of this vasoactive peptide in the EJV during migraine, we have measured its concentration in the external jugular vein of cats during cortical SD. This study demonstrates that SD has no effect on the concentration of CGRP either during the passage of a wave of spreading depression across the cortex or, 60 min later, during the period of post-SD cortical oligemia.

Animals↗
PubMed1993

Vasoactive peptides in Bartter's syndrome.

Patients with Bartter's syndrome exhibit an increased vascular resistance to the pressor effects of angiotensin II and noradrenaline. Further, an increased production of vasodilating renal prostaglandins, perhaps mediating the vascular unresponsiveness, has been hypothesized in this syndrome based on high urinary prostaglandins. To determine whether different peptides might contribute to blood pressure control in this syndrome, the basal immunoreactive plasma levels of an array of vasoactive peptides and catecholamines were analysed in six patients with Bartter's syndrome. Among the vasoconstrictors analyzed, the mean plasma levels of noradrenaline (NA), adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY-LI) were significantly increased as compared to healthy subjects (P = 0.030, 0.046 and 0.001, respectively). The plasma level of the vasodilator substance P (SP-LI) was also higher in these patients (P = 0.057). These results indicate that in Bartter's syndrome the vasoconstrictive effect of catecholamines and angiotensin II may be enhanced by concomitant NPY release. Whether a release of the vasodilator substance P is an independent mechanism or represents a reflex response to the increased secretion of angiotensin II, catecholamines and/or NPY remains to be established. However, the significance of these biochemical findings for blood pressure maintenance in Bartter's syndrome remains to be settled.

Adult↗
PubMed1993

CSF neuropeptides in cancer pain: effects of spinal opioid therapy.

The cerebrospinal fluid (CSF) levels of the opioid peptides met-enkephalin (ME), beta-endorphin (BE) and dynorphin (DYN) as well as the putative sensory neuropeptides substance P (SP), somatostatin (SOM), calcitonin gene related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were determined in 10 patients with severe nociceptive pain due to malignancy, before and after initiation of spinal opioid therapy, and in 10 control patients. Pain intensity, evaluated by means of a 100-mm visual analog scale (VAS), was reduced from 39 +/- 9 to 18 +/- 10 for continuous pain and from 70 +/- 10 to 10 +/- 8 for intermittent pain (means +/- s.e.mean). Lumbar CSF immunoreactive ME and DYN concentrations were significantly increased (P = 0.05) and BE and VIP were significantly decreased (P < or = 0.05) in the pain patients. A slight, but non-significant (P = 0.06) decrease in SP-like immunoreactivity was found after initiation of spinal opioid therapy. Visceral pain seemed to be associated with low immunoreactive SP and ME concentrations compared to somatic pain. A highly significant correlation was found between SP and ME (P < 0.001) and to a lesser extent also between other peptides. We conclude that the concentrations of the endogenous opioids were more affected by nociceptive pain states than the non-opioid peptides. The origin of pain may also influence the results. The postulated inhibition of peptide release by spinal opioid application seemed to be present for SP, but could otherwise not be confirmed.

Aged↗
PubMed1993

Changes in plasma levels of vasoactive peptides during standard bicarbonate hemodialysis.

During bicarbonate hemodialysis, there is an increase in peripheral vascular resistance of nonadrenergic origin, counteracting the hypotensive effect of fluid removal during the course of the dialysis. In this study, the plasma levels of vasoactive regulatory peptides, noradrenaline and renin, were investigated in 11 patients with chronic renal failure during standard bicarbonate hemodialysis (STHD) for 270 min. As regards vasoconstrictors, an increase in gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY) and plasma renin activity (PRA) occurred. However, arginine vasopressin and noradrenaline were unchanged. With respect to vasodilators, calcitonin gene-related peptide was not changed. An initial increase in beta-endorphin (beta-END) occurred, followed by a decrease during the remaining part of the treatment. Motilin decreased during the first part of the treatment but increased to the baseline level during the latter part. An increase in substance P was observed while vasoactive intestinal peptide decreased. We conclude that an increase in vasoconstricting substances (gamma 2-MSH, NPY, PRA) occurs during STHD, probably owing to the decrease in plasma volume. With the exception of beta-END, the changes in vasodilators were fairly small. The data suggest that vasoactive substances might participate in the hemodynamic response to hemodialysis.

Adult↗