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R Ekman

Publications and source records attributed to R Ekman.

304 records · Page 17Linked to original sources

Extraction and immunochemical characterization of delta sleep-inducing peptide-like material from the porcine pituitary and adrenal gland.

The naturally occurring forms of delta sleep-inducing peptide (DSIP) are not fully identified. In the present study, porcine pituitaries and adrenal glands were extracted in water, saline or acid under various conditions and immunoreactive DSIP (IR-DSIP) quantified by radioimmunoassay. The highest concentrations were measured in anterior pituitary extracts (40.8 +/- 2.6 ng/g tissue weight) recovered using water with aprotinin. However, high performance liquid chromatography (HPLC) indicated degradation of hydrophobic forms of IR-DSIP in water extracts. Extraction in acetic acid including C18 Sep-Pak purification resulted in an elution profile of IR-DSIP in adrenal extracts with a major peak coeluting with synthetic DSIP [DSIP(1-9)], whereas anterior pituitary extract showed material of higher hydrophobicity. Approximately 30% of IR-DSIP in anterior pituitary as well as in adrenal gland extracts seemed to be glucosylated, as based on concanavalin A chromatography. One of the DSIP-immunoreactive components by immunoblotting (molecular mass 25 kDa) was identified in both pituitary and adrenal gland extracts. In conclusion, several chromatographically distinct forms of IR-DSIP are present in the porcine pituitary and adrenal gland. IR material eluting as DSIP(1-9) is present in adrenal gland extract. The procedure and solution used for tissue extraction seem to be essential in order to obtain reliable elution positions on HPLC.

Adrenal Glands↗

Distribution and effects of neuropeptide Y, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide in human middle meningeal arteries: comparison with cerebral and temporal arteries.

A sparse to moderate supply of nerve fibers containing neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal polypeptide (VIP-LI), substance P (SP-LI), and calcitonin gene-related peptide (CGRP-LI) was demonstrated in the walls of human middle meningeal arteries. Comparison with similar studies on human cerebral and temporal arteries indicated a similar distribution and density. The immunoreactive material in all three arterial regions was characterized by reversed-phase high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA). The major peak of NPY-LI, VIP-LI, SP-LI, and CGRP-LI in each extract eluted approximately with the same elution volume as that of the corresponding synthetic analogues. The concentration of NPY in the middle meningeal arteries was lower as compared to the temporal arteries. Low concentrations of SP-LI and CGRP-LI were found in the middle meningeal arteries as compared to the cerebral arteries. In isolated ring segments of human middle meningeal and cerebral arteries, NPY caused vasoconstriction but did not potentiate the contractile response of noradrenaline. In the temporal artery, NPY did not induce contraction but potentiated the vasoconstrictor response to noradrenaline. Vasoactive intestinal polypeptide, peptide histidine methionine-27, SP, neurokinin A, and CGRP relaxed all three types of cephalic arteries. The peptide effects were not antagonized by propranolol, atropine, or cimetidine. Comparison of the responses to VIP and SP of vessels from the different regions showed a similar pattern of reactivity. The response to SP was slightly (p less than 0.05) more potent, whereas the responses to CGRP were less potent in the middle meningeal as compared to that in cerebral (p less than 0.005) vessels.

Acetylcholine↗

Bicycle injuries in Western Sweden: a comparison between counties.

The objectives of the study were to investigate whether there are differences in the incidence of bicycle-related injuries by geographic district (county), age, and gender in Sweden's Western Road Administration Region, and to utilize any detected differences to suggest priorities for intervention and prevention. Injury data come from the Swedish national hospital-discharge registry and a specialized national register of occupational injuries. Both bodily injuries in general and head injuries in particular show intra-regional differences. The rural part of Skaraborg County was shown to have a significantly higher injury incidence than other parts of the Western Region. Females generally show a lower incidence than males, but older women are more likely to be seriously injured than younger (age-related differences being greater than for males). Some striking findings were found with regard to occupational differences. Females sustain more work-related bicycle injuries than males. Head injuries account for more than half of the bicycle injuries in the Western Region that require hospitalization. All this indicates that targeted measures are required. Some studies have shown that the use of bicycle helmets reduces the incidence of head injuries, the degree of their severity, and the number of bicycle-related fatalities. There is a need for mandatory helmet-wearing legislation, which must go hand-in-hand with special efforts to reach groups with a low rate of helmet wearing, in particular those in the middle age range. Although the grown-up/older cycling population has been the subject of targeted action in some countries, the focus of preventive activity has generally been on children. The results of the study suggest the need for further injury-related research into adult cycling.

Accident Prevention↗

Effects of sham hemodialysis on plasma levels of vasoactive peptides in patients with uremia.

Changes in plasma levels of vasoactive peptides during hemodialysis have mainly been attributed to changes in plasma volume and osmolality. This study investigated the effect of the extracorporeal circulation on plasma levels of vasoactive peptides, noradrenaline, and renin. Eleven stable hemodialysis patients were studied during sham dialysis for 60 min using a Cuprophan dialyzer (Alwall GFE11, Gambro AB, Lund, Sweden). With regard to vasoconstrictors, there was an increase in noradrenaline (NA) (13%, p < 0.05) and renin (PRA) (32%, p < 0.05), while arginine vasopressin and neuropeptide Y remained unaltered. Concerning vasodilators, an increase in substance P (SP) (23%, p < 0.05) and vasoactive intestinal peptide (VIP) (15%, p < 0.01) was observed, while a decrease in atrial natriuretic peptide (ANP) (17%, p < 0.05) and motilin (MOT) (24%, p < 0.01) occurred. Calcitonin gene related peptide and beta endorphin were unaltered. A decrease in blood pressure was observed, while heart rate remained unchanged. The authors conclude that the extracorporeal circulation, per se, affects plasma levels of vasoactive substances and influences vascular stability. The decrease in ANP and MOT might be due to adsorption to the dialysis membrane. The increase in some vasoconstrictors (NA, PRA) and vasodilators (SP, VIP) might be induced by the blood-artificial surface contact, or by other factors, e.g., heparin or cooling of the blood during the procedure.

Adult↗

Dialysis fluid temperature and vasoactive substances during routine hemodialysis.

Blood pressure stability is better during cold hemodialysis (HD). This has mainly been attributed to a more pronounced sympathetic activation during cold than during warm HD. The authors studied the effect of dialysate temperature on vasoactive peptides, noradrenaline (NA), and renin (PRA). Ten hemodynamically stable patients were dialyzed for 240 min with each of two dialysate temperatures: 38.5 degrees C (warm HD = WHD) and 34.5 degrees C (cold HD = CHD). A decrease (P < 0.05) in blood pressure occurred during WHD; however, during CHD, blood pressure was stable. There were no differences in vasoconstrictors between the two regimens. There was a decrease in NA (P < 0.05), a tendency of PRA to increase (NS owing to a large statistical spread), while arginine vasopressin was unchanged. During CHD, there was a small increase in neuropeptide Y (NPY); however, during WHD, NPY only tended to increase. However, the relative NPY levels (percent of baseline levels) after WHD and CHD did not differ. The vasodilator response was similar during both treatments. Calcitonin gene related peptide was unaltered. Motilin tended to decrease initially, but then increased (P < 0.05) to baseline levels. An increase occurred in beta-endorphin (P < 0.05) and substance P(P < 0.01). There was an initial rise (P < 0.05) in vasoactive intestinal peptide (VIP), followed by a tendency to decrease during the remainder of treatment. The authors concluded that blood pressure stability was better during CHD. However, this was not reflected by differences in plasma levels of the vasoactive peptides, nor did they find any difference in the sympathetic drive between the two regimens.

Adult↗

Levels of immunoreactive insulin, neurotensin, and bombesin in porcine colostrum and milk.

High concentrations of insulin (411 +/- 214 microU/ml), neurotensin-like (265 +/- 72 pg/ml), and bombesin-like immunoreactivities (1995 +/- 288 pg/ml) were detected in porcine colostrum using radioimmunoassay, as compared to the levels found in sow blood serum at farrowing (5 microU/ml, less than 12 pg/ml, and 17 pg/ml, respectively). After 72 h of lactation, the levels of insulin and neurotensin-like immunoreactivities had decreased to 28 +/- 17 microU/ml and 89 +/- 23 pg/ml, respectively, while the bombesin-like activity remained constant. Characterization with reversed-phase high performance liquid chromatography showed that the insulin immunoreactivity eluted at the same position as the insulin standard, while the elution patterns of the neurotensin-like and bombesin-like immunoreactivities (eluted in three separate peaks) did not correspond to that of their respective standards. The biological function of the peptide hormones in colostrum/milk may be as triggers of the developmental changes taking place in the nursing neonate, especially in the gastrointestinal tract.

Animals↗

Intracerebroventricular administration of GM1 ganglioside to presenile Alzheimer patients.

We have conducted a preliminary study of the optimum conditions for a therapeutic effect of ganglioside GM1 in Alzheimer's disease. Five patients with the early onset form of Alzheimer's disease (AD type I) received the ganglioside by intracerebroventricular administration for 12 months. Bilateral stereotactic punction of the frontal horns of the ventricular system was performed, and shunt catheters were implanted and connected to a programmable pump. The optimum GM1 dose varied between 20 and 30 mg/24 h. Neurological neuropsychological, psychiatric and neurochemical examinations were performed 7 days before surgery and on days 30, 90, 180 and 360. No patient found the surgery difficult and no patient or relative regretted that they participated in the study. The patients became more active and safer in relation to others and to performance of various activities from day 90. The cerebrospinal fluid level of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased.

Aged↗

Chromogranin A in cerebrospinal fluid: a biochemical marker for synaptic degeneration in Alzheimer's disease?

Biochemical markers for AD would be of great value both to improve the clinical diagnostic accuracy in scientific studies and to increase the knowledge of the pathogenesis of the disorder. One of the main features of AD is a degeneration of synapses. Therefore, we examined if chromogranin A (CrA), the major protein of large dense-core synaptic vesicles, in cerebrospinal fluid (CSF) may be of value as a biochemical marker for the synaptic function in AD. The mean concentration of CrA in CSF was about 7.5 times higher than its concentration in serum, and there was no significant correlation between CSF-CrA and the blood-brain barrier function (measured as the CSF/serum albumin ratio), nor between CSF-CrA and serum-CrA. These findings suggest that the major portion of CSF-CrA is locally produced within the CNS. There were no significant differences in CSF-CrA between the AD (n = 29), vascular dementia (n = 13), and age-matched control (n = 9) groups (99.9 +/- 58.9 ng/ml, 108.0 +/- 69.4 ng/ml, and 115.1 +/- 44.4 ng/ml, respectively). However, when the AD group was subdivided into AD type I (n = 12) and AD type II (n = 17), a lower concentration of CSF-CrA was found in AD type I (72.8 +/- 28.9 ng/ml) compared with controls (115.1 +/- 44.4 ng/ml), p < 0.02, and compared with AD type II (119.1 +/- 67.5 ng/ml), p < 0.05, while CSF-CrA did not significantly differ between AD type II and controls. These findings suggest that CSF-CrA has a potential as a biochemical marker for the synaptic degeneration in AD type I, and gives further support for the relevance of identifying the AD type I (pure AD) subgroup in scientific studies.

Aged↗

Neuropeptides in cerebrospinal fluid of patients with Alzheimer's disease and dementia with frontotemporal lobe degeneration.

The two major primary degenerative dementias, dementia of Alzheimer type (DAT) and frontal lobe degeneration of non-Alzheimer type (FLD) have several clinical features in common but also many symptoms that differ. In a clinical material of 80 patients with either of the two forms of dementia (DAT = 39, FLD = 41) we have studied the levels of neuropeptides in the cerebrospinal fluid (CSF) in order to find biochemical markers for CNS affection. The dementia forms were evaluated by careful clinical analysis, psychometric testing and measurement of regional cerebral blood flow. Approximately one third of the subjects died during the completion of the study and neuropathology was performed, confirming the diagnoses. We observed reductions in the CSF levels of antidiuretic hormone and somatostatin in both DAT and FLD. A strong tendency to reduction was noted for neuropeptide Y (NPY). There was a correlation with the duration of disease demonstrating a significant reduction in NPY levels in subjects with DAT. Most notably there was a strong reduction in the levels of delta sleep inducing peptide (DSIP) in DAT cases only. The levels of DSIP in FLD were the same as in controls. The reverse was found for corticotropin releasing factor (CRF) which had a significant reduction in FLD patients but not in those with DAT. The present study indicates a difference in the CSF levels of neuropeptides, observations that these may serve as biochemical markers which differentiate DAT and FLD.

Adult↗

Dynamic aspects of regulatory lung peptides in chronic hypoxic pulmonary hypertension.

Male Sprague-Dawley rats were placed in hypobaric hypoxia for 17-21 d (FIO2 10%) to establish pulmonary hypertension (PH) and control rats were kept in normobaric room air. Right mean atrial and ventricular pressures (PRA, PRV) were recorded, left ventricular (LV) blood was collected, and lungs were perfused with heparinized saline. Hearts were removed to evaluate right ventricular (RV) hypertrophy (RV/(LV+septum)%). Peptides were quantitated with radioimmunoassay in lung tissue extracts and plasma. Wet lung weight, PRA, PRV, and RV/(LV+S)% were higher and body weight was lower in hypoxia rats, and lung morphometry revealed increased arterial medial thickness (MT/OD%) and elastification of arterioles and capillaries. Lung tissue CGRP, PYY, gamma 2-MSH, and SOM were higher in PH rats and ANP was unchanged. Blood AVP, CGRP, PYY, VIP, and SOM were reduced in PH rats and ANP was unchanged. Lung levels of PYY and SOM correlated significantly with the time in hypoxia and with all parameters examined and CGRP and gamma 2-MSH correlated with all but medial thickness. PYY had the highest correlation of the peptides with body weight, PRV, and RV/(LV+S)%, and SOM the highest with time in hypoxia, wet lung weight, PRA, MT/OD%, and elastification of arterioles and capillaries. Blood peptides correlated inversely with these parameters. ANP had the overall weakest correlations and CGRP, PYY, and SOM had the highest. SOM correlated the highest with arterial medial hypertrophy, PRV, RV hypertrophy, and elastification of peripheral capillaries. VIP correlated the highest of the blood peptides with body weight and wet lung weight. Statistically significant correlations do not necessarily imply causal relationships. The putative roles of these peptides in pulmonary function are discussed.

Animals↗

Cysteamine and pantethine effects on passive avoidance behavior, shuttle box learning, open-field activity, striatal catecholamines and somatostatin.

The effects of cysteamine and pantethine were compared on different behavioral tests and neurochemical parameters in rats. Cysteamine, administered in high dose (3.90 mM/kg s.c.), decreased the locomotor and rearing activities of rats, while it slightly but not significantly increased the avoidance latency in a passive avoidance test. Pantethine, 24 hr after its administration, significantly increased the dihydroxyphenyl acetic acid (DOPAC) levels in the striatum. Cysteamine slightly reduced the DOPAC level without influencing the catecholamine levels in this brain area. The striatal somatostatin concentration was reduced 24 hr after the administration of cysteamine, while pantethine did not influence it. After repeated daily injections of pantethine, the drug facilitated the shuttle box learning process and increased the intertrial and open-field activities of the animals. Cysteamine only slightly increased the locomotion and rearing and did not influence the shuttle box learning. Both pantethine and cysteamine slowed the rate of the "body weight increase" of the animals when compared to a saline-treated group. These findings suggest that the locomotor activation induced by pantethine 24 hr after its administration plays an important role in its behavioral effects. It might be that the striatal dopaminergic transmission, modified by administration of pantethine, plays some role in the higher locomotor activity induced by the substance.

3,4-Dihydroxyphenylacetic Acid↗

Cyclic fluctuations of vasoactive intestinal polypeptide measured radioimmunologically in various regions of the human fallopian tube.

Levels of the neuropeptide VIP were measured by radioimmunoassay in the isthmus, ampulla, and fimbriated end of the human fallopian tube during the follicular, ovulatory, and luteal phases as defined by plasma estradiol and progesterone concentrations. The regional concentration of VIP was in the order isthmus greater than ampulla greater than fimbriae. The VIP concentration increased by 170% from the follicular through the ovulatory to the luteal phase in the isthmus. Such a tendency was seen also in the ampulla when the peptide level was expressed in terms of the total regional content. In fact, when expressed as total content, VIP was highest in the ampulla at all cyclic stages. Since there are no major fluctuations in the water content of the tubal tissues in the three phases, the observed changes in VIP levels represent real fluctuations at the neural level in a manner similar to that previously shown for the neurotransmitter norepinephrine.

Adult↗

Insulin involvement in intestinal macromolecular transmission and closure in neonatal pigs.

The involvement of insulin in the intestinal transmission of macromolecules to blood and the cessation of this transport (intestinal closure) was studied in neonatal pigs by measuring the serum levels of the markers bovine serum albumin and fluorescein isothiocyanate labelled dextran 70,000 (FITC-D) at 4 h after gavage feeding. In naturally suckled pigs, intestinal closure at 18 h was shown to be associated with an increase in serum immunoreactive insulin (IRI) levels. Similarly, intestinal closure obtained at 18 h, by gavage feeding unsuckled pigs a total of 48 g lactose/kg, was accompanied by an increase in serum IRI levels. Neither high serum IRI levels nor closure were observed in fasted pigs or in pigs gavage fed a total of 12 g lactose/kg. The effect of exogenous insulin on intestinal macromolecular transmission was studied by injecting 5 IU insulin/kg subcutaneously at 3 and 6 h, respectively, in newborn pigs gavage fed 10 ml sow colostrum/kg at 3 h intervals. This resulted in a reduction in the transmission of the markers when tested at 12 h, in comparison to littermates receiving the same amount of colostrum and littermates suckling the sow. It appears as if insulin, reflected as high serum levels over an extended period of time, is involved in the regulation of macromolecular transmission and intestinal closure in neonatal pigs. It was speculated that insulin may be involved in these processes by initiating the synthesis of membrane structural proteins in the enterocytes.

Animals↗

Expression of hydra head activator in newt tissues and effects on limb regeneration.

In this study, the presence of the hydra head activator (HHA) neuropeptide and its influence on regenerating newt limbs (Notophthalmus viridescens) was investigated. Immunohistological analysis has localized the HHA neuropeptide in the adult newt brain, eye, intestine, and regenerating blastema. Experiments in which 9 day limb regenerates were denervated and subsequently implanted with HHA-soaked beads suggest a slight progression of blastema growth compared to denervated controls.

Amino Acid Sequence↗

Tissue concentrations of gastrointestinal regulatory peptides in the duodenal mucosa in systemic sclerosis.

OBJECTIVE: Esophageal hypomotility and abnormalities of intestinal function are important manifestations in systemic sclerosis (SSc), but their pathogenesis is not well understood. Since there is evidence that plasma concentrations of certain gastrointestinal regulatory peptides are increased in SSc, we were interested in examining the peptide concentrations and localization in biopsy specimens from the intestinal mucosa in SSc patients. We studied 12 patients with gastrointestinal disease. METHODS: Levels of corticotrophin-releasing hormone (CRH), motilin, neuropeptide Y (NPY) and peptide YY (PYY) were determined by radioimmunoassay and high-performance liquid chromatography (HPLC), and the occurrence of motilin, PYY, somatostatin, and NPY were studied with immunohistochemistry. RESULTS: Except for the concentrations of CRH, which were increased 2-fold, the tissue concentration of motilin, NPY and PYY were decreased by approximately 50% among patients with esophageal and intestinal dysfunction (group B) compared to patients with impaired esophageal motility alone (group A). In addition, HPLC-characterization of motilin, NPY, and PYY showed a different pattern of fragments among patients in groups A and B. In all patients duodenal motilin, PYY, and somatostatin were localized in the endocrine cells. The distribution and frequency of the cells did not differ among the patients. NPY was localized to neuronal elements; there was no overt difference among the patients with respect to the frequency of NPY-containing nerves. CONCLUSION: This study shows that patients with widespread gastrointestinal disease have lower tissue concentrations of regulatory peptides compared to patients with less widespread disease.

Adult↗