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Biomedical subjects

R Ekman

Publications and source records attributed to R Ekman.

At least 217 records · Page 12Linked to original sources

Neuropeptide Y and peptide YY as possible cerebrospinal fluid markers for major depression and schizophrenia, respectively.

Neuropeptide Y (NPY)-like and peptide YY (PYY)-like immunoreactivities were measured in cerebrospinal fluid (CSF) from patients with major depressive disorder or schizophrenia and from healthy volunteers without physical or mental illness. NPY-like material was significantly lower (P less than 0.001) in CSF of patients with depressive disorders than in schizophrenic patients or healthy controls. Treatment with the antidepressant, amiflamine, a selective MAO-A inhibitor, did not alter CSF peptide concentrations. In drug-free schizophrenic patients, normal NPY but reduced PYY concentrations in CSF were observed. Treatment with neuroleptics did not affect the levels of NPY or PYY in the CSF. The finding of reduced CSF concentrations of NPY in patients with major depression and of reduced PYY concentrations in schizophrenia may reflect disturbed synthesis, turnover or degradation of the peptides. These findings suggest that the reduced concentrations of NPY or PYY in the CSF may be used as trait markers of the respective illnesses.

Adolescent↗

Neuropeptide Y and vasoactive intestinal peptide coexist in rat thyroid nerve fibers emanating from the thyroid ganglion.

Neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) occur in nerve fibers around blood vessels and between follicles in the thyroid gland of the mouse and rat. VIP-immunoreactive fibers are numerous, while NPY-immunoreactive fibers are fewer. Most of the latter fibers contain noradrenaline (NA) as well as NPY, while a subpopulation was found to contain VIP instead of NA. We have determined the origins of rat thyroid nerve fibers containing NPY, VIP or NPY/VIP by investigating 3 conceivable sources, i.e. the superior cervical ganglion, the nodose ganglion and the thyroid ganglion. Chemical sympathectomy or removal of the superior cervical ganglion did not affect the frequency of VIP-immunoreactive fibers but eliminated most of the NPY-immunoreactive fibers as well as all NA-containing nerve fibers (recognized by antibodies to dopamine-beta-hydroxylase). The NPY-immunoreactive fibers that remained after sympathectomy occurred around blood vessels and between follicles and contained VIP. Cervical vagotomy (removal of the nodose ganglion including the adjacent vagus) did not overtly affect the frequency of NPY/VIP-, VIP-, or NPY/NA-containing fibers in the thyroid. In contrast, extirpation of the thyroid ganglion, which is situated immediately outside the thyroid capsule, greatly reduced the number of VIP- and NPY/VIP-containing fibers in the rat thyroid. On the whole, the results of radioimmunoassay of NPY and VIP agreed well with the immunocytochemical findings. High performance liquid chromatography confirmed the identity of NPY and VIP. The present findings suggest the existence in the rat thyroid of one NPY-containing nerve fiber population that harbours NA and emanates from the superior cervical ganglion; one NPY-containing fiber population that is non-adrenergic, harbours VIP and originates in the thyroid ganglion; and a second VIP-containing fiber population that is devoid of NPY and appears to derive from the thyroid ganglion.

Animals↗

Calcitonin gene-related peptide in hamster lung and its coexistence with serotonin: a chemical and immunocytochemical study.

The mammalian lung may have an important endocrine function besides being involved in gas exchange mechanisms. A number of peptide hormones have been localized to neurons and endocrine cells in the lung where they may contribute to the regulation of local pulmonary functions. We have investigated the presence of calcitonin gene-related peptide (CGRP), in the hamster lung by radioimmunoassay and by immunocytochemistry. Measurable quantities of CGRP were detected in lung tissue. Females had higher lung tissue levels of CGRP-like immunoreactivity (IR) than males. This was not reflected in an observable increase in the intensity or distribution of CGRP-like reactivity with immunocytochemistry. Distinct CGRP-like IR was recorded in clustered (NEB) and solitary (NEC) neuroendocrine cells in neonates, weanlings and adults, including all airways from trachea (NEC only) to bronchi, bronchioles, and alveolar ducts to the level of alveoli (NEC and NEB). In adult hamsters, there seemed to be fewer immunoreactive cells, although intensity was unchanged. In addition some NEB contained serotonin-like IR, and colocalization of the peptide and the amine was noted within some cells. Intra-epithelial beaded nerve fibers, subepithelial fibers, and large-caliber nerves in the hilus region and tracheal wall were also CGRP-IR, and immunoreactive nerves were occasionally found in close association with NEB at the basal pole. Positive nerve fibers were not observed in vessels within the lung, and were sparse in the adventitia of tracheal arteries.

Animals↗

Hypergastrinaemia evoked by omeprazole stimulates growth of gastric mucosa but not of pancreas or intestines in hamster, guinea pig and chicken.

Treatment of chickens, hamsters and guinea-pigs with the long-acting anti-secretagogue omeprazole resulted in elevated levels of serum gastrin. The chickens received 400 mumol/kg by i.m. injection once daily, the hamsters and guinea-pigs received the same dose by the oral route once daily. In all 3 species omeprazole raised the intragastric pH to 4, measured 12-14 h after the administration of the drug. After 10 weeks of treatment, trophic changes were observed in the stomach of hamster and guinea pig and in the proventriculus of chicken. The trophic changes were manifested in a greatly increased stomach weight and gastric mucosal mass. There were no trophic effects outside the stomach (or proventriculus). The results are in agreement with previous observations in the rat and support the view that long-lasting sustained hypergastrinaemia causes trophic changes in the stomach but not in the pancreas or in the intestines.

Animals↗

Calcitonin gene-related peptide in rat salivary glands: neuronal localization, depletion upon nerve stimulation, and effects on salivation in relation to substance P.

Calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibres occurred predominantly around blood vessels and large ducts and, to a minor extent, around acini and small ducts in the parotid, sublingual and submaxillary glands of the rat. Double immunostaining showed most of the CGRP-containing nerve fibres to contain substance P. However, the vast majority of substance P-immunoreactive periacinar nerve fibres in the parotid and submandibular glands lacked CGRP. After parasympathetic denervation of the parotid gland by section of the auriculotemporal nerve these periacinar substance P-immunoreactive nerve fibres disappeared almost completely, whereas the number of substance P/CGRP-immunoreactive nerve fibres seemed unchanged. After this operation the total amount of substance P in the parotid gland was reduced by about 90% as judged by radioimmunoassay; in denervation experiments the facial nerve was found to contribute to the residual substance P content. In contrast, the contribution of the auriculotemporal nerve to the CGRP content of the gland was small; the reduction in CGRP after section of the nerve was 20%. The facial nerve and the dorsal root nerves (C3 and C4) contributed to the CGRP content with about 50%. The source of the remaining 30% of the parotid gland CGRP is unknown. It is not the sympathetic nerve: sympathetic denervation resulted in a marked increase in CGRP, regardless of whether the auriculotemporal nerve was intact or not. Upon long-lasting electrical stimulation of the auriculotemporal nerve at a high frequency the parotid gland content of CGRP was gradually reduced, indicating depletion of this peptide in response to nerve stimulation. Intravenous injections of CGRP evoked no salivary flow; however, a release of amylase was revealed. Also, when CGRP was tested on isolated parotid gland lobules amylase was released into the medium. When, in vivo, CGRP was injected in combination with substance P, the substance P-evoked flow of parotid and submaxillary saliva was markedly enhanced. In addition, CGRP enhanced the in vivo secretory response to parasympathomimetics and to vasoactive intestinal peptide. The localization of CGRP-containing nerve fibres suggests that CGRP is involved in the regulation of secretion and blood flow of salivary glands. CGRP may interact positively with acetylcholine and certain nonclassical transmitters, and it may be involved (together with other neuropeptides) in the atropine-resistant parasympathetic secretion occurring in the glands under study.

Amylases↗

Projections of peptide-containing neurons in rat colon.

The distribution, origin and projections of nerve fibers containing vasoactive intestinal peptide, substance P, neuropeptide Y, galanin, gastrin-releasing peptide, calcitonin gene-related peptide, somatostatin or enkephalin were studied in the midcolon of the rat by immunocytochemistry and immunochemistry. Most of these nerve fibers had an intramural origin as was established by extrinsic denervation (serving of mesenterial nerves). Extrinsic denervation eliminated neuropeptide Y-containing fibers of presumably sympathetic origin together with sensory nerve fibers containing both substance P and calcitonin gene-related peptide. Co-existence of two peptides in the same neuron was studied by double immunostaining. This revealed co-existence of neuropeptide Y and vasoactive intestinal peptide in one population of intramural neurons; an additional population of intramural neurons was found to contain vasoactive intestinal peptide but not neuropeptide Y. All somatostatin-containing neurons in the submucous ganglia were found to harbor calcitonin gene-related peptide. A much larger population of submucous neurons containing calcitonin gene-related but not somatostatin was also detected. Some perivascular calcitonin gene-related peptide-containing nerve fibers (of intrinsic origin) harbored vasoactive intestinal peptide while others (of extrinsic origin) harbored substance P. The polarities and projections of the various peptide-containing intramural neurons in the transverse colon were studied by analysing the loss of nerve fibers upon local disruption of enteric nervous pathways (myectomy or intestinal clamping). Myenteric neurons containing vasoactive intestinal peptide, galanin, gastrin-releasing peptide, calcitonin gene-related peptide, somatostatin or vasoactive intestinal peptide/neuropeptide Y gave off 5-10-mm-long descending projections while those containing substance P or enkephalin issued approx. 5-mm-long ascending projections. Submucous neurons containing calcitonin gene-related peptide, somatostatin/calcitonin gene-related peptide or gastrin-releasing peptide issued both ascending (2-6 mm) and descending (2-6 mm) projections, those containing vasoactive intestinal peptide issued ascending (approx. 2 mm) projections, while those containing galanin or vasoactive intestinal peptide/neuropeptide Y lacked demonstrable oro-anal projections. Enkephalin-containing fibers could not be detected in the mucosa and the mucosal substance P-containing nerve fibers were too few to enable us to delineate their projections.

Animals↗

Return of nerve fibers containing gastrin-releasing peptide in rat small intestine after local removal of myenteric ganglia.

Gastrin-releasing peptide is a neuropeptide with a wide distribution in the rat small intestine. Most of the GRP-containing fibers are intramural in origin. Local severing of myenteric GRP neurons by circumferential removal of the outer longitudinal muscle layer together with the adherent myenteric ganglia (myectomy) in a segment of the rat jejunum resulted in the disappearance of GRP fibers from the myectomized circular muscle and from myenteric ganglia and both muscle layers for approximately 10 mm anally to the lesion. As examined at different time intervals up to 60 weeks postoperatively fine-varicose GRP fibers of a normal appearance were found to return gradually to the portion anal to the lesion beginning at 20 weeks, first in the more distal portions and then (after 40-60 weeks) also in the more proximally located portions. Also the circular muscle in the myectomized segment became reinnervated during this time period. These fibers were notably coarse, more numerous than in control circular muscle, and arranged in thick bundles (hyperinnervation). Such nerve bundles were particularly frequent 40 weeks after the operation. The results indicate a remarkable plasticity of enteric neurons.

Animals↗

Topical anesthesia with lidocaine aerosol in the control of postoperative pain.

Postoperative pain was assessed in patients undergoing inguinal hernia repair. Ten patients received lidocaine aerosol in the surgical wound before skin closure, ten patients received placebo aerosol devoid of lidocaine, and ten patients were untreated. The lidocaine-treated group had significantly lower pain scores and meperidine requirements during the first postoperative day compared to the control groups. During the second day after surgery, these variables did not differ between groups. Wound anesthesia, assessed by palpation of the wound 24 h after surgery by a blinded investigator, was significantly more pronounced in the group treated with lidocaine aerosol than in the control groups. Similarly, in patients undergoing bilateral herniorraphy, wound pain following palpation was significantly reduced on the lidocaine-treated side compared to the untreated side. Patients in the group receiving lidocaine aerosol indicated less pain in connection with mobilization than untreated patients, but not compared to patients treated with placebo aerosol. Plasma substance P (SP) and beta-endorphin (BE) measured in lidocaine-treated patients and in untreated patients before and after drug administration showed no significant differences regarding SP, while BE was significantly increased 1 h after surgery in the untreated group. Plasma lidocaine concentrations were well below toxic levels. Results show that lidocaine aerosol used as topical anesthetic in the surgical wound is simple to use, and results in a long-lasting reduction of pain after a single administration. Moreover, postoperative mobilization is facilitated, and the requirement for postoperative analgesics is reduced. Wound healing was normal, and no adverse reactions to lidocaine were reported.

Adult↗

Increased plasma levels of peptide YY in coeliac disease.

Peptide YY (PYY) is exclusively localized in endocrine cells in the gut, and these cells are most numerous in the distal small intestine, colon, and rectum. We have earlier shown that PYY coexists with enteroglucagon in the gut endocrine cells. High basal and postprandial plasma enteroglucagon concentrations have earlier been found in patients with untreated coeliac disease. PYY circulates in human plasma and is detectable in most healthy adults. We have therefore studied the basal PYY levels in patients with coeliac disease. Marked elevated basal plasma PYY levels were found in patients with coeliac disease compared with an age- and sex-matched control group. The PYY levels were inversely correlated to the concentration of folate acid in serum. The PYY levels were studied in four patients with newly diagnosed disease and had normalized within 8 months on a gluten-free diet.

Adolescent↗

Psychologic preparation program for children undergoing acute appendectomy.

A psychologic preparation program was developed for use prior to emergency surgery in children. The purpose of this study was to determine whether specific information prior to an emergency operation would reduce anxiety. The effect of the preparation program was evaluated with clinical and laboratory procedures. One group of children who received only general verbal information was compared with another group who received specific information. The subjects were 24 patients and their parents. The children were studied at four different clinical units prior to operation, using the Visual Analogue Scale and pulse rate and blood pressure measurements. Stress hormone levels were measured at three of these clinical units. Visual Analogue Scales were administered to parents three times prior to the child's operation. The results were analyzed for within-group differences from one clinical unit to the next and for between-group differences at the various clinical units. The results indicated less anxiety in the children who received specific information. Catecholamine and beta-endorphin measurements were not greatly different between the groups.

Acute Disease↗

Evaluation of cross-reactivity of urinary digoxin-like substance in different radioimmunoassays.

For the accuracy of routine monitoring of digoxin and digitoxin it seems important to get information on the cross-reactivity of endogenous digitalis-like substances (EDLS). To obtain EDLS, urine was passed on Sep-Pak columns and eluted in fractions by increasing concentrations of acetonitrile. Dilution series of two fractions were subjected to radioimmunoassay (RIA) with respect to digoxin- and digitoxin-like activity, using commercial kits from New England Nuclear, Farmos Diagnostica, and Diagnostic Products Corporation. Cross-reactivity and the degree of parallelism between dilution curves and standard curves varied markedly between the procedures. Recovery studies showed that the presence of EDLS, even at concentrations below the limit of determination of the respective assay, can influence the recovery of digoxin and digitoxin. When higher concentrations of EDLS were present, the combined effects of EDLS and drugs were not always additive. This again stresses the need for any RIA to be carefully characterized to minimize important sources of errors. Required prerequisites are detailed and highly specific information on specificity and the influence of endogenous interfering substances is given. To warrant reliable measurements of digoxin, it is important to identify the cross-reactive material known as EDLS.

Adult↗

Partial characterization of endogenous digoxinlike substance in human urine.

Urinary samples were collected from individuals not taking cardiac glycosides. Aliquots of 30 ml were passed through preparative octadecylsilane-bonded phase columns and eluted in fractions by stepwise increasing concentrations of acetonitrile. Eluted fractions were analysed for their contents of endogenous digoxinlike substance (EDLS) by radioimmunoassay of digoxin and by a bioassay of cardiac glycosides, which measures the uptake of rubidium (86Rb) by erythrocytes as an index of Na+, K+-ATPase activity. In both assays, digoxinlike activity was found in several fractions, but the highest values were consistently measured in the fractions eluted with 40% acetonitrile. Greater amounts of EDLS were recovered from the urine of pregnant women than from the urine of men and nonpregnant women.

Acetonitriles↗

Neuropeptide Y (NPY) in the area of the hypothalamic paraventricular nucleus activates the pituitary-adrenocortical axis in the rat.

Immunocytochemical studies have documented the presence of neuropeptide Y (NPY) in the hypothalamic paraventricular nucleus (PVN) which harbours a large number of neurones that contain corticotrophin-releasing factor (CRF). In this study the close morphological association between NPY fibres and CRF cell bodies in the PVN was confirmed. The localization of NPY terminals in the vicinity of CRF neurones forms a morphological basis for an action of NPY in the hypothalamic control of the pituitary-adrenocortical axis. We therefore microinjected NPY into the area of the PVN of both conscious, freely moving and anaesthetized rats and noted a powerful stimulatory effect on adrenocorticotropic hormone (ACTH) and corticosterone release as measured by radioimmunoassay. In experiments with conscious, freely moving rats, higher ACTH and corticosterone levels were detected following injection of NPY into the area of the PVN than following control injection (desamidated NPY). Intracerebroventricular injection of NPY produced a small, albeit significant, increase in circulating corticosterone levels as compared to control (saline-injected) rats. Anaesthetized rats responded to NPY (but not to saline) injected into the area of the PVN with elevated ACTH and corticosterone levels, while injection of NPY into the neocortex failed to affect the blood concentration of either ACTH or corticosterone. In conclusion, we have demonstrated an activating effect of NPY on the pituitary-adrenocortical axis both in conscious and anaesthetized rats which may reflect the anatomical relationship between NPY fibres and CRF neurones in the PVN.

Adrenocorticotropic Hormone↗

Peptide-containing nerve fibers in human cerebral arteries: immunocytochemistry, radioimmunoassay, and in vitro pharmacology.

Nerve fibers containing neuropeptide Y, vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) were seen in the adventitia or at the adventitia-media border of human cerebral arteries obtained during neurosurgical procedures. Radioimmunoassay of human cerebral arteries, removed at autopsy, revealed that the levels of the four peptides did not differ among the major cerebral arteries. There was, however, a gradual decline in peptide concentrations with increasing age of the patients, as measured in the proximal part of the middle cerebral artery. Pharmacological experiments on fresh segments of cerebral (pial) arteries in vitro revealed that neuropeptide Y caused vasoconstriction per se but did not potentiate the contractile response of noradrenaline. VIP, peptide histidine methionine-27 (PHM-27), SP, neurokinin A (NKA), and human CGRP potently relaxed vessels precontracted by prostaglandin F2 alpha, the relative potency being human CGRP greater than SP greater than VIP greater than NKA greater than PHM-27. The amount of relaxation varied between 55% (SP) and 96% (human CGRP) of the prostaglandin F2 alpha-induced contraction. The peptide effects were not antagonized by propranolol, atropine, or cimetidine, suggesting an action that does not involve adrenergic, cholinergic, or histaminergic receptors.

Age Factors↗

Occurrence of substance P, vasoactive intestinal peptide, and calcitonin gene-related peptide in dermographism and cold urticaria.

Substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) were assayed in lesions and normal skin of patients with dermographism and cold urticaria utilizing suction-induced blisters. There was no difference in SP and VIP concentrations between challenged and control skin of urticaria patients. On the whole, however, the concentration of both neuropeptides, and VIP in particular, was higher in the urticaria patients than in control subjects. CGRP levels were not increased. SP and VIP in blood samples from veins draining challenged skin areas were below the detection limit. It is concluded that SP and VIP may potentiate histamine in wheal formation and thus contribute to the increased reactivity of the skin to trauma and temperature changes in patients with physical urticaria.

Adult↗

gamma 2-[corrected]-MSH-like immunoreactivity in porcine pituitary and adrenal medulla. An immunochemical and immunocytochemical study.

A sensitive and specific radioimmunoassay for gamma 2-melanotropin (gamma 2-MSH) has been developed that does not recognize alpha-, beta-, gamma 1- or gamma 3-MSH. gamma 2-MSH-like immunoreactivity could be demonstrated in the porcine pituitary and adrenal gland. The highest concentrations were detected in the neurointermediate lobe regardless of extraction procedure. The anterior lobe harboured lower concentrations and in adrenal gland extracts only small amounts were measured. Gel chromatography and high performance liquid chromatography of extracts of both pituitary and adrenal gland revealed several peaks of immunoreactive material, one of which eluted close to the position of synthetic gamma 2-MSH. By immunocytochemistry gamma 2-MSH immunoreactivity was localized to the adrenocorticotropin/alpha-MSH cells in the pituitary and to a subpopulation of the noradrenaline-storing cells in the adrenal medulla. Together, the immunocytochemical and immunochemical findings indicate the existence of gamma 2-MSH-like material in the porcine pituitary and adrenal medulla.

Adrenal Medulla↗

Novel N-terminal fragments of pro-gamma-melanocyte-stimulating hormone isolated from pig pituitary.

Two novel N-terminal fragment pairs of porcine pro-gamma-melanocyte-stimulating hormone (MSH)-(1-103), viz. pro-gamma-MSH-(1-30)/(2-30) and pro-gamma-MSH-(1-67)/(2-67) were characterized. A third pair of peptides of still larger size was also detected. The two characterized peptide pairs terminate at sites different from the dibasic sequences typical of prohormone cleavage. This suggests either a different processing event or proteolysis during purification; in both cases cleavages are selective since the two peptides end at distinct positions. Unlike most previously described pro-gamma-MSH forms, which begin with Trp at position 1 in pro-opiomelanocortin (position -105 in relation to the start of ACTH), the novel peptide pairs show N-terminal heterogeneity with one of the components beginning with Trp as in other forms, and the second component (present in relative amounts of 10-70%) beginning with Cys at position 2 (corresponding to position -104).

Amino Acid Sequence↗

Projections of peptide-containing neurons in rat small intestine.

The distribution, origin and projections of nerve fibers containing vasoactive intestinal peptide, neuropeptide Y, somatostatin, substance P, enkephalin and calcitonin gene-related peptide were studied in the rat jejunum by immunocytochemistry and immunochemistry. Their origin was determined by the use of various procedures for extrinsic denervation (chemical sympathectomy, bilateral vagotomy or clamping of mesenterial nerves). The terminations of the different types of intramural nerve fibers were identified by examination of the loss of nerve fibers that followed local disruption of enteric nervous pathways (intestinal myectomy, transection or clamping). The majority of the peptide-containing nerve fibers in the gut wall were intramural in origin, each nerve fiber population having its own characteristic distribution and projection pattern. Nerve fibers emanating from the myenteric ganglia terminated within the myenteric ganglia and in the smooth muscle layers: those storing vasoactive intestinal peptide/neuropeptide Y, somatostatin and substance P were descending, those storing enkephalin were ascending and those containing calcitonin gene-related peptide projected in both directions. Nerve fibers emanating from the submucous ganglia terminated mainly within the submucous ganglia and in the mucosa: those storing calcitonin gene-related peptide or vasoactive intestinal peptide/neuropeptide Y were ascending and those storing substance P or somatostatin were both ascending and descending. Enkephalin nerve fibers could not be detected in the mucosa.

Animals↗