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Biomedical subjects

R Ekman

Publications and source records attributed to R Ekman.

At least 199 records · Page 11Linked to original sources
PubMed1989

Acetylcholine and vasoactive intestinal peptide in cerebral blood vessels: effect of extirpation of the sphenopalatine ganglion.

The innervation of cerebral blood vessels by nerve fibers containing acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) and the vasomotor effects of the two neurotransmitters have been analyzed in the rat following the uni- or bilateral removal of the sphenopalatine ganglion (SPG), which is thought to be the major origin of this innervation. Histochemistry of AChE-positive nerve fibers and the immunoreactivity toward VIP revealed only a 30% reduction in the innervation pattern of the rostral part of the cerebral circulation following the operation. At approximately 4 weeks postoperatively, the original nerve network was restored. Quantitative measurements of cholineacetyltransferase activity and VIP revealed similar reductions in the levels of collected large cerebral arteries at the base of the brain and in small pial vessels overlying the cerebral cortex at the various postoperative times following uni- or bilateral removal of the SPG. The two techniques thus complemented each other. Vasomotor reactivity to acetylcholine (ACh) and VIP was examined in proximal segments of the middle cerebral artery at the various postoperative times. Generally, the removal of the SPG had no effect on the responses to ACh or VIP. The evidence indicates that only approximately one-third of the cholinergic/VIP innervation of the rostral part of the cerebral circulation originates in the SPG.

Acetylcholine↗
PubMed1989

Lidocaine treatment of painful diabetic neuropathy and endogenous opioid peptides in plasma.

Intravenous infusion of lidocaine has a pain-relieving effect in patients with painful diabetic neuropathy. We measured plasma beta-endorphin (beta-EP), dynorphin immunoreactivity (DYN), and met-enkephalin (MET) before and after lidocaine infusion in 8 patients with painful diabetic neuropathy and in 10 controls. The pretreatment level of beta-EP and DYN was identical in the two groups. After lidocaine, beta-EP increased in diabetic patients from 3.4 to 5.5 pmol/L (median) (p less than 0.02) and in controls from 3.4 to 5.0 pmol/L (p less than 0.02). The concentration of DYN was stable, and MET was undetectable before and after lidocaine. Lidocaine reduced symptoms and pain score in diabetic patients was uncorrelated with the changes in beta-EP. Intravenous lidocaine increased plasma beta-EP and diminished complaints in patients with painful diabetic neuropathy.

Adult↗
PubMed1989

Circulating perivascular dilatory neuropeptides in hypertension.

Little is known about perivascular neuropeptides in hypertension in man. In this study we investigated the circulating levels of calcitonin gene-related peptide (CGRP)-, substance P- and vasoactive intestinal peptide-like immunoreactivity in 30 patients with severe hypertension before and after treatment for high blood pressure. Circulating levels of CGRP- and substance P-like immunoreactivity in the hypertensives were significantly different from the corresponding levels in 31 age- and sex-matched normotensive subjects. After normalization of blood pressure the mean levels of CGRP- and substance P-like immunoreactivity did not differ between the two groups. The levels of vasoactive intestinal peptide-like immunoreactivity remained unchanged. These observations suggest that vascular afferent nerves play a part in the maintenance of hypertension.

Adult↗
PubMed1989

Effects of capsaicin pretreatment on neuropeptides and salivary secretion of rat parotid glands.

1. 'Atropine-resistant' secretion of saliva in response to parasympathetic stimulation may reflect antidromic activation of sensory nerve fibres. In this investigation, the effect of pretreatment in the rat with capsaicin (total dose of 125 mg kg-1, s.c.), was determined. 2. In the parotid glands substance P (SP)/calcitonin gene-related peptide (CGRP)-containing nerve fibres around ducts and blood vessels disappeared after capsaicin, while periacinar SP-containing fibres (devoid of CGRP) and CGRP-containing fibres (devoid of SP) remained. Vasoactive intestinal peptide (VIP)-containing nerve fibres seemed to be unaffected. The parotid content of SP and CGRP was reduced by 11 and 36% respectively, while that of VIP remained unchanged. 3. The weights of the parotid glands and their sensitivity to the secretagogues methacholine and SP, injected intravenously, were unchanged as was the response to stimulation of the auriculo-temporal nerve in the presence and absence of atropine. 4. In contrast to capsaicin pretreatment, parasympathetic denervation of the parotid gland reduced the weight of the gland and produced an increase in the response to methacholine and SP. 5. For comparison, the effectiveness of the capsaicin treatment on neuropeptide content was determined in the urinary bladder. The bladder of capsaicin-pretreated rats increased in weight (21%) and in VIP content (31%), while the content of SP and CGRP was reduced by 86 and 94%, respectively. SP- and CGRP-containing nerve fibres were virtually eliminated, while VIP-containing nerve fibres seemed unaffected. 6. In conclusion, antidromic activation of primary afferent (capsaicin-sensitive) C-fibres does not contribute significantly to the 'atropine-resistant' secretory response of the parotid gland to stimulation of the parasympathetic nerve.

Animals↗
PubMed1989

Capsaicin evokes secretion of nasal fluid and depletes substance P and calcitonin gene-related peptide from the nasal mucosa in the rat.

1. The secretion of nasal fluid was studied in anaesthetized rats after topical application of capsaicin, and of calcitonin gene-related peptide (CGRP) alone or CGRP in combination with substance P (SP). The flow of nasal fluid was stimulated and the secretions collected by a filter paper technique. The concentrations of SP and CGRP in nasal biopsies were determined after topical or systemic administration of capsaicin. 2. Capsaicin (single dose administration) stimulated nasal secretion in a dose-dependent manner. The effect was inhibited by hexamethonium, lignocaine, or by the tachykinin antagonist (D-Pro2, D-Trp7,9)-SP, but not by atropine, or by a combination of the histamine H1-receptor antagonist chlorpheniramine and the H2-receptor antagonist ranitidine. 3. When applied cumulatively, capsaicin rapidly produced desensitization. The concentrations of SP and CGRP in the nasal mucosa were reduced by capsaicin 6 days after topical or s.c. administration but not 15 min after topical application of desensitizing doses. 4. CGRP did not stimulate the secretion of nasal fluid and did not alter SP-evoked nasal secretion. 5. The inhibition by hexamethonium of the capsaicin-evoked nasal secretion suggests the involvement of ganglionic reflexes. In addition, the inhibition of the response to capsaicin by (D-Pro2,D-Trp7,9)-SP and lidocaine and the depletion of SP and CGRP after capsaicin indicate the involvement of tachykinin-mediated axon reflexes.

Animals↗
PubMed1989

Low CSF met-enkephalin levels in cluster headache are elevated by acupuncture.

Significantly lower met-enkephalin levels were found in CSF from cluster headache sufferers as compared to age-matched healthy volunteers, whereas it was not possible to demonstrate any clear-cut difference for beta-endorphin. CSF opioid levels may rise following manual or electroacupuncture. It was studied whether traditional Chinese (manual) acupuncture affected CSF levels of met-enkephalin or beta-endorphin in these patients, and to what extent this treatment would be beneficial for the headache. A significant rise in lumbar CSF met-enkephalin levels was found, whereas no clear change in beta-endorphin levels was obtained. The treatment was, however, of little value in preventing the headache.

Acupuncture Therapy↗
PubMed1989

Elevated CSF somatostatin concentrations in demented patients parallel improved psychomotor functions induced by integrity-promoting care.

Elderly demented patients from 2 nursing homes participated in this study. An experimental group (n = 17) was subjected to a 3-month program with integrity-promoting care resulting in emotional, intellectual and physical activation, whereas a control group (n = 18) had no change from the regular ward care. Dementia rating scales and psychological tests were administered before the start of the study and at the end of the 3-month study period. Lumbar punctures were performed at the same time for assessment of neuropeptide concentrations (somatostatin (SRIF), arginine vasopressin (AVP) and corticotropin-releasing factor) in the cerebrospinal fluid (CSF). In the control group no significant changes were found in the ratings before and after the study. In contrast, improvements in intellectual and motor functioning were observed in the experimental group. Concomitantly, the SRIF concentrations in CSF were significantly elevated in the experimental group and not affected in the control group. The CSF AVP concentrations were reduced in both groups at the end of the study, but considerably more in the control group. It is concluded that environmental factors can improve intellectual and motor functioning in demented patients and also alter CSF biochemical measures of dementia.

Aged↗
PubMed1989

Calcium stimulates the release of calcitonin gene-related peptide from the canine thyroid.

The calcitonin gene in the thyroid parafollicular cells generates two different mRNAs, which encode for the precursors of calcitonin and calcitonin gene-related peptide (CGRP). In this study, we investigated whether these two peptides are released simultaneously in the perfused dog thyroid. The isolated dog thyroid (n = 10) was once-through perfused with a Krebs-Ringer bicarbonate buffer. After elevation of the buffer Ca2+ concentration from 1.5 to 2.5 mM, a rapid, marked, and parallel secretion of both calcitonin and CGRP occurred (P less than 0.001). By stepwise increase of the buffer Ca2+ concentration, it was found that, although an elevation from 1.5 to 1.65 mM had no influence on the thyroid output of calcitonin or CGRP, elevations to 1.75, 2.0, and 2.5 mM of Ca2+ induced dose-dependent parallel increases in the thyroid output of calcitonin and CGRP. Furthermore, the stimulation with pentagastrin (100 pM) increased the thyroid output of both calcitonin and CGRP in parallel. It is concluded that the normal dog thyroid releases calcitonin and CGRP in parallel on stimulation with Ca2+ and pentagastrin.

Animals↗
PubMed1989

Immunoreactive delta sleep-inducing peptide secretion from mouse dissociated, anterior pituitary cells: regulation by corticotropin-releasing factor and arginine vasopressin.

Immunoreactive delta sleep-inducing peptide (IR-DSIP) has previously been localized to the ACTH/MSH cells of the human and porcine pituitary gland. In the present report, the distribution of IR-DSIP in the mouse pituitary gland was examined by immunocytochemistry. In this species, IR-DSIP was found to be co-localized with thyroid-stimulating hormone (TSH) in anterior pituitary thyrotrophs and was also present in nerve fibers in the posterior and intermediate lobes. The effect of synthetic DSIP on IR-ACTH release from dissociated mouse anterior pituitary cells was also studied. DSIP (greater than or equal to 10(-9) M) inhibited both basal and CRF-induced IR-ACTH release from these cells. In addition, the effect of synthetic rat corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) on IR-DSIP secretion was investigated. CRF and AVP at concentrations of 10(-11)-10(-7)M inhibited release of IR-DSIP from mouse anterior pituitary cells by 63%. When CRF and AVP (10(-10)-10(-7) M) were given concomitantly, the maximal inhibition of IR-DSIP release was observed at a concentration of 10(-8)M of CRF and AVP. However, these two peptides when given together showed no additive effect on IR-DSIP secretion. These findings suggest that during CRF induction of ACTH secretion from anterior pituitary corticotrophs, CRF may also act simultaneously to inhibit DSIP secretion from the thyrotrophs.

Adrenocorticotropic Hormone↗
PubMed1989

Increased tissue concentration of neuropeptide Y in the duodenal mucosa in coeliac disease.

Neuropeptide Y (NPY) is localized to intestinal nerve fibres, of which there are few in normal duodenal mucosa. In the duodenal mucosa of 10 patients with coeliac disease and in a control group of 21 patients with other gastrointestinal symptoms but with normal function of the small intestine we studied the frequency of such fibres by immunohistochemistry and the tissue concentration of NPY by radioimmunoassay. Patients with coeliac disease had an increased number of NPY nerve fibres and significantly elevated tissue concentrations compared with the control group. The eluted fractions obtained by high-pressure liquid chromatography of duodenal extracts showed the same immunoreactive components in the two groups. This study therefore suggested proliferation of the peptide-containing nerve system in coeliac disease. The increased NPY levels in the duodenal mucosa may be of functional significance for the disease symptoms.

Adult↗
PubMed1989

Reduced levels of calcitonin gene-related peptide (CGRP) but not substance P during and after treatment of severe hypertension in man.

Little is known of the significance of perivascular peptides in hypertension. In this study we have investigated the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P- like immunoreactivity (SP-LI) during and after treatment of severe hypertension. Seventeen patients with a mean blood pressure of 204/127 mmHg were included. Circulating levels of CGRP-LI and SP-LI in normotensive controls were 35 +/- 4 and 1.2 +/- 0.1 pmol/l, respectively. In the hypertensives CGRP-LI was significantly lower (22 +/- 3 pmol/l: P less than 0.05) while SP-LI did not differ (1.6 +/- 0.3 pmol/l) from the normotensives. After treatment the circulating level of CGRP-LI was still significantly lower (16 +/- 2 pmol/l: P less than 0.001) while SP-LI remained unchanged when compared with the controls. These observations suggest an involvement of vascular afferent nerves in the aetiology of hypertension in man.

Adrenergic beta-Antagonists↗
PubMed1989

Dietary fibre enrichment, blood pressure, lipoprotein profile and gut hormones in NIDDM patients.

The influence of a beet-fibre enriched diet (mean 40 g FibrexR, 27 g dietary fibre per day) on blood pressure, plasma lipoproteins and glycaemic control was studied in 12 non-insulin-dependent diabetic (NIDD) patients. The effect on gastrointestinal hormones was also investigated. Beet-fibre and control diets were given in randomized order for 8 weeks each. During the beet-fibre diet the systolic blood pressure decreased (P less than 0.05) and the HDL-cholesterol levels increased (P less than 0.05) compared to values before the study. There was a tendency for systolic blood pressure to be lower also in the control period, but this was not statistically significant. After both diet periods the total plasma cholesterol and triglyceride levels decreased, as well as the LDL/HDL ratio. Blood glucose levels--fasting or postprandial--and glycosylated haemoglobin were not affected during the two different diet periods. In obese NIDD patients, however, the postprandial insulin levels were lower after the beet-fibre diet compared to the control diet. This subgroup also showed lower fasting values of pancreatic polypeptide and motilin were recorded for the obese patients after the fibre-rich period compared to before the study. Further, increases in postprandial motilin levels, 60-180 min, were found after the fibre-rich period. Investigations with reference to an entero-hormonal mechanism by measuring neurotensin and peptide YY did not show any variations between the diet periods.

Adult↗
PubMed1988

Antidepressant drugs increase the concentration of neuropeptide Y (NPY)-like immunoreactivity in the rat brain.

Rats were given imipramine or zimeldine orally for three weeks and the brain levels of neuropeptide Y-like immunoreactivity (NPY-LI) were measured. The concentration of NPY-LI in frontal cortical tissue was elevated by 40 and 60%, respectively. Imipramine increased the concentration of NPY-LI in the hypothalamus by 65% while zimeldine was without effect. The concentration of NPY-LI in the parietal cortex was unaffected by either of the drugs. These observations support the hypothesis that NPY might be involved in the pathophysiology of depressive illness.

Animals↗
PubMed1988

Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system.

The trigeminal ganglion was activated, in humans by thermocoagulation as part of the treatment of trigeminal neuralgia and in cats by electrical stimulation, and blood samples were taken from the external jugular vein for estimates of plasma levels of substance P and calcitonin gene-related peptide (CGRP). In those patients who were noted at the time of coagulation to have flushed there were marked elevations of the local (cranial) levels of both peptides. However, in the nonflushing patients no changes in the peptide levels were observed. Parallel experiments in the cat revealed that the levels of substance P-like and CGRP-like immunoreactivity were increased during electrical stimulation of the trigeminal ganglion. The observation of elevation of substance P-like and CGRP-like immunoreactivity after activation of the nociceptive afferent system of the head provides new insights into a putative role of peptides in the pathophysiology of migraine and cluster headache, and suggests new areas of possible therapeutic intervention.

Animals↗
PubMed1988

Oxygen toxicity in the infant rhesus monkey: effects on regulatory peptides in lung and blood.

A total of ten 6-month-old male rhesus monkey (Macaca mulatta) infants, born full-term, were positive-pressure ventilated with greater than 95% oxygen or room air (controls). A protocol was used which closely simulated pediatric intensive care. To test if regulatory peptides were affected by the oxygen treatment, and to search for an early marker of oxygen toxicity, lung tissue samples and systemic mixed venous blood were collected at 6, 12 and 24 hours after onset of treatment. The peptides, gastrin releasing peptide (GRP), calcitonin gene-related peptide (CGRP), peptide YY (PYY), vasoactive intestinal peptide (VIP) and somatostatin (SOM), were quantitated in lung tissue extracts and plasma using radioimmunoassay. Lung tissue GRP, CGRP, and PYY levels appeared to decrease gradually with time, perhaps as a result of the positive pressure ventilation procedure. GRP and CGRP levels decreased less among monkey infants ventilated with oxygen, thus they were significantly higher at 24 hours than in air ventilated controls. VIP levels were significantly lower among tests compared to controls at that time. Blood peptide levels did not change with oxygen treatment. These results suggest that tissue concentrations of certain pulmonary regulatory peptides can become altered by ventilation with greater than 95% oxygen. A blood borne peptide marker was not identified.

Animals↗
PubMed1988

Delta sleep-inducing peptide response to human corticotropin-releasing hormone (CRH) in major depressive disorder. Comparison with CRH-induced corticotropin and cortisol secretion.

Twenty-four subjects (12 patients with major depressive disorder and 12 controls matched for sex and age) received 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) as an iv bolus dose. Healthy subjects exhibited a slight, but sustained, increase of plasma delta sleep-inducing peptide (DSIP) concentrations, whereas a marked reduction of DSIP levels was found in depressives. Compared to controls, depressed patients showed a significant attenuation of corticotropin (ACTH) responses, whereas cortisol secretion in response to hCRH was normal. Basal DSIP and cortisol concentrations were highly correlated and were higher in depressives than in controls. Both were negatively correlated with the DSIP responses to hCRH. These findings are compatible with the hypothesis that hypothalamic-pituitary-adrenal (HPA) overactivity in the depressive state is primarily due to central hypersecretion of CRH and support the view of a modulatory function of DSIP in the complex regulatory mechanism of the HPA system and of its pathophysiological significance for aberrant HPA axis function in major depressive disorder.

Adrenocorticotropic Hormone↗