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Biomedical subjects

P Venge

Publications and source records attributed to P Venge.

At least 19 recordsLinked to original sources
PubMed1992

Blood eosinophil numbers and activity during 24 hours: effects of treatment with budesonide and bambuterol.

The effects of the inhaled corticosteroid budesonide and the oral long-acting beta-agonist bambuterol on circadian variation of blood eosinophil numbers, serum levels of eosinophil cationic protein (ECP), serum eosinophil chemotactic activity (ECA), and serum neutrophil chemotactic activity (NCA) were studied in two groups of patients with allergic asthma. Group 1 (n = 8) had a circadian variation of peak expiratory flow (PEF) 15% or greater, and group 2 (n = 9) had a circadian PEF variation less than 15%. Both groups were randomized and crossover treated for 4 weeks with (A) 0.4 mg budesonide at 8 AM and 8 PM, (B) 20 mg bambuterol at 8 PM, and (C) placebo. At the end of each period blood eosinophil numbers, ECP, ECA, and NCA were measured during 24 hours at 4-hour intervals. No significant differences in the inflammatory parameters could be observed between the groups, although eosinophil numbers tended to be higher in group 1 than in group 2. Highest eosinophil numbers were observed at night. Budesonide reduced both eosinophil numbers and ECP levels, especially at night; bambuterol had no effect on both variables. No circadian variation or treatment effects were observed for ECA and NCA. This study suggests a role for the eosinophil in the nocturnal worsening of asthma, and it demonstrates that budesonide produces, in contrast to bambuterol, a reduction of (nocturnal) eosinophil numbers and activity.

Adolescent↗
PubMed1992

Degranulation of eosinophils from pollen-atopic patients with asthma is increased during pollen season.

The secretion of granule proteins from eosinophils and neutrophils was studied in isolated cells, obtained from 11 pollen-atopic patients with asthma, twice during and twice outside pollen season. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase (MPO) were measured by means of specific radioimmunoassay (RIA). Eosinophils from the pollen-atopic patients obtained during pollen season released significantly more (p less than 0.02) ECP and EPX than cells from the same patients obtained before pollen season. The released amount of ECP and EPX was correlated (r = 0.54; p less than 0.003) to the total pollen count. The release of MPO from neutrophils was only raised (p less than 0.01) at the end of the pollen season. Serum concentrations of ECP and EPX and blood eosinophil counts were significantly raised (p less than 0.002, p less than 0.001, and p less than 0.009, respectively) before pollen season and increased further at the end of the pollen season. There were no changes in lung function during pollen season and consequently no discernible relationships to eosinophil and neutrophil degranulation. We conclude that eosinophils and, to some extent, neutrophils from birch pollen-atopic subjects have an increased propensity to secrete their granule proteins during a pollen season. We suggest that these cells have been primed as a consequence of allergen exposure.

Adolescent↗
PubMed1992

Heparin-coated circuits reduce activation of granulocytes during cardiopulmonary bypass. A clinical study.

Activated granulocytes release highly active enzymes such as myeloperoxidase and lactoferrin, which can be involved in tissue destruction mediated by oxygen free radicals. Cardiopulmonary bypass has been reported to activate granulocytes. Bypass circuits coated with heparin have been shown to reduce release of granulocyte factors in experimental studies. In the present study, heparin-coated circuits were compared with noncoated circuits. In seven patients undergoing coronary bypass, heparin-coated circuits were used (group HC), and seven served as control patients (group C). In group HC the heparin dose was reduced to 75% (225 IU/kg). Group C had the standard dose of 300 IU/kg. No preoperative differences in myeloperoxidase and lactoferrin were observed between the groups. At the end of bypass in both groups, there was a significant increase of these enzymes (p less than 0.001) followed by a later decrease. In group HC, however, the release of myeloperoxidase was significantly lower than in group C (215 +/- 24 versus 573 +/- 133 micrograms/L, mean +/- standard error of the mean). The release of lactoferrin was significantly lower in group HC than in group C both at the end of cardiopulmonary bypass (659 +/- 79 versus 1448 +/- 121 micrograms/L) and 3 hours after bypass (224 +/- 37 versus 536 +/- 82 micrograms/L). Granulocytes as well as total number of leukocytes continued to increase until 1 hour after bypass (p less than 0.001) and then manifested a slow decrease. It was concluded that the use of heparin-coated circuits reduced the release of granulocyte factors because of lower activation of leukocytes.

Biochemical Phenomena↗
PubMed1992

Eosinophil cationic protein alters proteoglycan metabolism in human lung fibroblast cultures.

Eosinophil cationic protein (ECP), a highly basic protein secreted from eosinophilic granulocytes, has been shown to take part in the inflammatory reaction. The involvement of ECP in fibroblast activation was therefore investigated in cell culture. Production of proteoglycans, hyaluronan and collagen in the presence of ECP was measured after incorporation of radioactive precursors and separation into different proteoglycan classes using gel and ion exchange chromatography and hydrophobic interaction chromatography. Proteoglycan accumulation in the cell layer was increased two- to fivefold at an ECP-concentration of 10 micrograms/ml. No effect on collagen, other proteins or hyaluronan was noted. Furthermore, no effect was observed on cell proliferation. The increased proteoglycan accumulation could be inhibited by addition of heparin or of antibodies to ECP. The effect could not be mimicked by the two basic peptides protamine and poly-L-lysine, speaking in favor of specificity. The increase in proteoglycan material was seen exclusively in the intracellular pool. No change of proteoglycans in the medium or the cell surface-associated pool was noted. The increase in the cell layer was accounted for by a two- to fivefold increase in free chains of heparan sulfate and dermatan sulfate. No change was seen in the proteoglycan pattern. No effect on proteoglycan synthesis or on endocytosis was noted. The increased accumulation of polysaccharide was caused by inhibited degradation of glycosaminoglycans. The half-lives of large and small heparan sulfate proteoglycans/glycosaminoglycans and dermatan sulfate proteoglycans/glycosaminoglycans in the cell layer are increased four- to sevenfold. We conclude that ECP inhibits proteoglycan degradation in fibroblasts, which indicates a role for the eosinophil in generation of fibrosis.

Blood Proteins↗
PubMed1991

Detection of eosinophil cationic protein (ECP) by an enzyme-linked immunosorbent assay.

Eosinophil cationic protein (ECP) is a highly basic and potent cytotoxic single-chain zinc-containing protein present in the granules of the eosinophilic granulocytes. ECP appears to be involved in defence against parasites and in the tissue damage seen in subjects with allergic and inflammatory disease. To investigate ECP release from in vitro activated human eosinophils and to study the involvement of eosinophils in health and disease, we have developed a sensitive and specific enzyme immunoassay. ECP was purified from normal human peripheral blood eosinophils and polyclonal antibodies to ECP were subsequently raised in rabbits. The ELISA utilizes the biotin/avidin method and measures ECP within the range 15-1000 ng/l. The intra- and interassay coefficients of variation were 6% and 10%, respectively, and the recoveries of 12 and 25 pg of purified ECP added to diluted serum samples were 108 +/- 14.5% (mean +/- SD, n = 12) and 107 +/- 7.5%, respectively. The high sensitivity, reproducibility and specificity of this ELISA makes it suitable for the determination of minute amounts of ECP in in vitro systems as well as in various biological fluids.

Blood Proteins↗
PubMed1991

Blood eosinophil number and activity in relation to lung function in patients with asthma and with eosinophilia.

Blood eosinophil count, serum concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO), and peak expiratory flow (PEF) rate were studied in 23 patients with severe labile asthma characterized by eosinophilia at the start and end of a treatment period of 5 weeks. The mean blood eosinophil count was 808 x 10(6)/L at the start of the treatment period. Serum ECP and EPX were significantly raised compared with that of the references, whereas the mean serum MPO level was normal. The mean PEF was significantly and negatively correlated to both blood eosinophil count and serum ECP and EPX, but the predominant correlation was that between blood eosinophil count and PEF. At the end of the treatment period, PEF had increased and the blood eosinophil count and serum ECP and EPX were reduced when these values were compared with the values at the start of the treatment period. There was a significant and negative correlation of mean PEF to serum ECP but not to the blood eosinophil count. In individual subjects, the decreases in the blood eosinophil counts and serum EPX were significantly correlated to the individual increases of mean PEF. In conclusion, the present investigation indicates that in patients with asthma and pronounced eosinophilia, the lung function of the patients was principally related to the number of circulating eosinophils, whereas, when their eosinophilia was reduced to moderate levels, the patient's lung function was closer related to the activity of the eosinophils.

Adolescent↗
PubMed1991

Indirect evidence of bronchial inflammation assessed by titration of inflammatory mediators in BAL fluid of patients with asthma.

Bronchial inflammation is a characteristic of asthma that may be examined indirectly by bronchoalveolar lavage (BAL). Nine normal individuals were compared with 38 age-matched adults with asthma of variable severity to appreciate the importance of cell activation in the severity of asthma. The severity of asthma was appreciated by the clinical score of Aas and the pulmonary function of the patients. FEV1 ranged between 35% and 130% of predicted. The indirect activation of eosinophils (EOSs), mast cells, fibroblasts, and neutrophils was examined by the titration of eosinophil cationic protein (ECP), tryptase, hyaluronan (HA), and myeloperoxidase (MPO) by radioimmunoassay in BAL fluid (BALF) and cytology of BALF. In the adults with asthma, there was a significantly increased number of EOSs and a significantly increased level of all mediators but MPO. MPO levels were increased in seven patients only; three of these patients were previous smokers. Only ECP and HA levels were significantly correlated with the severity of asthma. These results demonstrate EOSs, mast cells, and fibroblasts are activated in asthma, whereas the involvement of neutrophils is less clear. There was a significant correlation between ECP and HA levels, suggesting a common activation of EOSs and fibroblasts.

Adult↗
PubMed1991

Eosinophils in exercise-induced asthma.

The variations in serum levels of eosinophil cationic protein (ECP) have been measured after exercise challenge of 13 patients with asthma with exercise-induced asthma (EIA) and nine patients with asthma without EIA. The patients were treated before exercise in a randomized and blinded fashion with inhalation of one dose of either disodium chromoglycate, terbutaline, or budesonide and in an open study with 4 weeks of inhaled budesonide. In the group with EIA, there was, in some patients, an initial increase in serum levels of ECP after exercise, but 60 minutes after exercise, the levels were significantly reduced (p less than 0.001). Disodium chromoglycate and 4 weeks of budesonide treatment inhibited this reduction. Histamine challenge of the group with EIA produced a similar fall in serum ECP levels (p less than 0.001). The group without EIA had initially lower levels of ECP than the group with EIA (p less than 0.05 to p less than 0.01), and ECP stayed unaltered after exercise. The preexercise serum ECP levels correlated significantly to the maximal fall in peak expiratory flow in the untreated group (r = 0.91; p less than 0.001) and in the group receiving one dose of budesonide (r = 0.62; p less than 0.05). The blood eosinophil counts were unchanged after challenge and not related to lung function. The results suggest that the ECP content in serum reflects the degree of allergic inflammation in the lungs and thereby the degree of bronchial hyperreactivity.

Adolescent↗
PubMed1991

Secretion of granule proteins from eosinophils and neutrophils is increased in asthma.

The activity of eosinophil and neutrophil granulocytes with respect to secretion of granule proteins was studied in 30 patients with asthma and with varying severity of their disease. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase was measured by means of specific radioimmunoassays. Eosinophils from patients with asthma released significantly more (p less than 0.001) ECP and EPX after 20 minutes of incubation than cells from control subjects without asthma. The release of myeloperoxidase from neutrophils was also somewhat higher (p less than 0.03). The serum concentrations of ECP and EPX were also significantly increased (p less than 0.001) in the group with asthma. No significant relationships were found between clinical variables and the secretory activity of either eosinophils or neutrophils. We conclude that eosinophils and, to some extent, neutrophils from subjects with asthma have an increased propensity to release their granule proteins, which we suggest is a consequence of priming of these cells.

Adult↗
PubMed1991

The effect of immunotherapy on eosinophil accumulation and production of eosinophil chemotactic activity in the lung of subjects with asthma during natural pollen exposure.

Two groups of birch pollen--allergic patients with seasonal rhinoconjunctivitis and asthma were followed during two consecutive birch-pollen seasons, one group, N = 10, during a season with high pollen load, and one group, N = 15, during a season of low pollen load. Half the patients were treated with immunotherapy (IT) for 3 and 4 years, respectively. The other half of the patients served as control group (non-IT). Bronchoalveolar lavage (BAL) was performed once before each season and once during the pollen season. Eosinophil (EOS) numbers in BAL were increased (p less than 0.01) during the season with high pollen load but not in the season with a low pollen load, and this increment was absent in the IT-treated group. Also, the EOS cationic protein levels were raised in the non-IT-treated group during the season with a high pollen load. The levels of EOS and neutrophil chemotactic activity were raised in BAL in both seasons in the non-IT-treated group compared with the IT-treated group (p less than 0.02, p less than 0.003, p less than 0.04, and p less than 0.005 in high- and low-load pollen season, respectively). Serum and BAL eosinophil chemotactic activity (ECA) were positively correlated (p less than 0.001). We conclude that there is an influx of active EOSs into the lung of pollen-allergic patients with asthma during a pollen season, which may be abrogated by IT. Furthermore, the generation of ECA appears to be an extremely sensitive marker of antigenic exposure, and the potent inhibition of the generation of ECA by IT may provide a clue as to the mechanism of this treatment.

Adolescent↗
PubMed1991

Muscle ATP and lactate and the release of myoglobin and carbanhydrase III in acute lower-limb ischaemia.

Serum-myoglobin and carbanhydrase III (S-CAIII), a specific muscle enzyme, were measured on admission, during surgery and in the postoperative period in 23 patients with acute lower-limb ischaemia and in 21 patients with chronic limb ischaemia in order to evaluate these molecules as possible markers of the degree of clinical ischaemia. The muscle contents of ATP and lactate were determined in muscle biopsies from patients with acute ischaemia on admission. Unlike S-myoglobin and S-CAIII they discriminated between cases which required subsequent amputation from those which did not. Clinical signs of ischaemia were, however, of no value in this respect and there were no correlations between clinical signs or the duration of ischaemia and S-myoglobin or S-CAIII or the contents of ATP or lactate in muscle tissue. The levels of S-myoglobin and S-CAIII correlated well (r = 0.95, p less than 0.0001). In patients who subsequently required an amputation S-myoglobin increased ten-fold (i.e., from 24-48 h postoperatively in acute arterial ischaemia and from 3 h postoperatively in patients with chronic limb ischaemia). In patients with a successful revascularisation S-myoglobin returned to normal levels. It is concluded that in this investigation S-myoglobin had no prognostic value on admission and that S-myoglobin analyses in the postoperative course may be useful for making clinical decisions concerning impending recirculation failures.

Acute Disease↗
PubMed1991

Radioimmunoassay of human eosinophil cationic protein (ECP) by an improved method. Establishment of normal levels in serum and turnover in vivo.

A radioimmunoassay was developed allowing measurement of the cytotoxic cationic ECP. The assay, which has a total incubation time of 3.5 hr, is a double antibody assay with radiolabelled ECP, covering the concentration range of 2-200 micrograms/l. Performance data show a detection limit of less than 2 micrograms/l and a cross-reactivity with eosinophil protein X (EPX/EDN) of less than 0.06%. The coefficient of variation (%) within the measuring range was, within assay 4.8-10.4, and total 6.6-12.0. The assay is useful for measurement in various body fluids including serum, nasal secretions and bronchoalveolar lavage fluid, and dilution of samples prior to analysis was generally not required. Sera from 100 apparently healthy individuals revealed a geometric mean of 6.0 micrograms ECP/l and a range (95%) of 2.3-15.9 micrograms/l. The elimination rate of ECP, t1/2, in vivo was estimated to be 65 min when ECP was measured in serum. Comparisons between this assay and a method previously described showed that the new method is superior with regard to precision and assay procedure.

Blood Proteins↗
PubMed1991

Eosinophils, secretory responsiveness and glucocorticoid-induced effects on the nasal mucosa during a weak pollen season.

This study examined the seasonal effects on eosinophils and secretory responsiveness of the nasal mucosa in 22 patients with allergic rhinitis due to birch pollen (11 patients received placebo and 11 budesonide, 200 micrograms once daily in each nostril). The pollen counts during the study season were too low to produce a significant symptomatology. Hence, our findings demonstrate threshold alterations of the airway mucosa in allergic rhinitis and their inhibition by anti-inflammatory drug intervention. The patients were monitored for 8 weeks with daily recordings of pollen counts and symptom scores. Once every week a series of laboratory tests was carried out: the local eosinophil influx was determined using a Rhinobrush technique; the levels of eosinophil cationic protein (ECP) were analysed in nasal lavage fluids; and the secretory response to intranasal methacholine was measured. Treatments started after a 2-week run-in period. The proportion of eosinophils increased markedly in the placebo group and was elevated also during the last two study weeks when the pollen counts were practically nil. The secretory responsiveness to methacholine increased during the pollen season and returned to baseline towards the end of the study period. The topical glucocorticoid treatment reduced the proportion of eosinophils, the ECP levels, and the secretory response to methacholine compared to placebo. We conclude that the increased traffic and activity of eosinophils and less conspicuously the increased secretory responsiveness are expressions of the mucosal inflammation that precede the development of symptoms in seasonal allergic rhinitis.

Administration, Intranasal↗
PubMed1991

In vitro studies of the interaction between heparin and eosinophil cationic protein.

Eosinophil cationic protein (ECP) is a protein specific to the granules of human eosinophil granulocytes, ECP is highly cationic and may damage tissue if not inactivated. Heparin is a highly anionic substance present in mast cells and basophil granulocytes. The present in vitro study shows that ECP can inactivate the anticoagulant activity of heparin probably by the formation of a complex between the two molecules. This function may be of importance for the microenvironment of allergic diseases where secretion of heparin may promote penetration of mast cell products through tissues. Also this may constitute one mechanism whereby the cytotoxic action of ECP is neutralized.

Blood Coagulation↗
PubMed1991

Increased chemokinetic and chemotactic responses of eosinophils in asthmatic patients.

The aim of the present study was to investigate the migratory responses of eosinophil and neutrophil granulocytes from asthmatic patients compared with granulocytes from healthy individuals. Twenty-three patients with unstable and severe asthma and blood eosinophilia (greater than 400 x 10(6) cells/l) were selected for the study. Eosinophil and neutrophil chemotactic and chemokinetic responses were tested twice, at the beginning and end of a 5 week treatment period. Lung function was followed by daily measurements of PEF. The eosinophils of the asthmatics demonstrated increased chemokinetic responses to albumin, autologous serum, and normal human serum (NHS), and an increased chemotactic response to NHS at the beginning of the treatment period compared with eosinophils from the references. At the end of the period the eosinophil chemokinetic responses to albumin, autologous serum and NHS were still increased and so was the chemotactic response to zymosan-activated serum (ZAS). The neutrophil migratory responses were not increased compared with those of the references, except for the chemokinetic response to autologous serum, which was increased both at the beginning and end of the treatment period. Patients in whom the eosinophil migratory responses, to most of the agents used, decreased over the treatment period, demonstrated a significantly greater improvement of their lung function at the end of the period compared with patients in whom the eosinophil migratory responses increased. However, no direct relationship between eosinophil migratory responses and lung function of the patients was found. In conclusion, the present investigation demonstrated increased migratory responses of eosinophils from asthmatic patients. This enhanced responsiveness is proposed to be due to priming of the eosinophils in vivo, and might be one mechanism behind the selective recruitment of eosinophils to the lungs of asthmatics.

Adolescent↗
PubMed1991

Reduced granulocyte activation with a heparin-coated device in an in vitro model of cardiopulmonary bypass.

Granulocyte activation during cardiopulmonary bypass (CPB), resulting in degranulation, may have adverse effects. Fresh whole human blood and priming solution was circulated through oxygenator/tubing sets coated with functional heparin (n = 7) and through uncoated sets (n = 7) in model CPB. Plasma concentrations of the primary granule protein myeloperoxidase (MPO) and the secondary granule protein lactoferrin (LF) were measured in radioimmunoassays, and the neutrophils were counted. After 120 min, seven to nine times baseline concentrations of LF (p less than 0.0001) were observed with both devices. Increases of MPO were also significant, but significantly larger (p less than 0.01) with the uncoated devices. There was an equivalent reduction in neutrophil numbers in both groups. MPO did not bind to heparin-coated Sephadex particles in gel chromatography. Thus, the heparin coating most likely prevented the release of potentially harmful primary granule proteins, indicating improved biocompatibility. Adhesion of neutrophils and exocytosis of LF, which may be involved in adhesion, were unaffected.

Biocompatible Materials↗