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Biomedical subjects

C G Persson

Publications and source records attributed to C G Persson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Histamine-induced airway mucosal exudation of bulk plasma and plasma-derived mediators is not inhibited by intravenous bronchodilators.

Experimental data suggest the possibility that common bronchodilators, such as the xanthines and beta 2-adrenoceptor agonists, may produce microvascular anti-permeability effects in the subepithelial microcirculation of the airways. In this study, we have examined the effect of bronchodilators given intravenously on exudation of different-sized plasma proteins (albumin and fibrinogen) and the generation of plasma-derived peptides (bradykinins) in human nasal airways challenged with histamine. In a double-blind, crossover, placebo-controlled and randomised trial, 12 normal volunteers were given i.v.infusions of terbutaline sulphate, theophylline and enprofylline to produce therapeutic drug levels. The effect of topical nasal provocation with histamine was closely followed by frequently nasal lavage with saline. The lavage fluid levels of albumin, fibrinogen and bradykinins increased significantly after each histamine provocation. The ratio of albumin-to-fibrinogen in plasma and the lavage fluid was 24 and 56, respectively, indicating that topical histamine provocation induced a largely non-sieved flux of macromolecules across the endothelial-epithelial barriers. The systemically administered drugs did not affect the nasal symptoms (sneezing, secretion and blockage), nor did they significantly reduce the levels of plasma proteins and plasma-derived mediators in the nasal lavage fluids. The present data suggest that systemic xanthines and beta 2-adrenoceptor agonists, at clinically employed plasma levels, may not affect the microvascular (and epithelial) exudative permeability and the bradykinin forming capacity of human airways.

Adolescent↗
PubMed1994

Human nasal absorption of 51Cr-EDTA in smokers and control subjects.

Passive exposure to cigarette smoke has emerged as a significant risk factor in the development of asthma and allergic airways disease. The pathogenetic mechanisms are not known, but increased absorption across the airway epithelial lining has been suggested as one possible mechanism of this effect of cigarette smoke. This study examines the absorption-permeability of the nasal epithelial lining in cigarette smokers and non-smokers. For comparison, the effect of a detergent, dioctylsodium sulfosuccinate (DS), is also examined. A solution containing 51Cr-EDTA (51-chromium labeled ethylene diamine tetraacetic acid) (mol. wt. 372 Da) was instilled and maintained in the nasal cavity in six smokers and 12 non-smokers for 15 min. Urine was collected for 24 h after the instillation. The accumulated amount of excreted 51Cr-EDTA was measured and expressed as millilitre nasal instillate. In six non-smokers the procedure was repeated when DS has been added to the instillate. The median recovered amount of 51Cr-EDTA in smokers 0.07 ml (range 0.04-0.32) was not significantly different from that in non-smokers 0.16 ml (0.01-1.22). The recovered amount of 51Cr-EDTA increased from a median of 0.18 ml (0.01-1.22) to 1.13 ml (0.53-1.80) after addition of the detergent (P = 0.028). We conclude that the nasal airway absorption-permeability is not increased in smokers. Hence, passive exposure to cigarette smoke may not produce an impairment of airway barrier functions.

Absorption↗
PubMed1994

Glucocorticoid-induced attenuation of mucosal exudation of fibrinogen and bradykinins in seasonal allergic rhinitis.

The mucosal plasma exudate with its proteins, enzymes, derived peptides, and matrix molecules is an important factor in inflammatory airway diseases. This study investigated whether topical glucocorticosteroid treatment influences mucosal exudation of bulk plasma (fibrinogen) and the generation of plasma-derived mediators (bradykinins) in seasonal allergic rhinitis. Twenty-two patients with birch-pollen-induced allergic rhinitis participated in a double-blind, randomized, placebo-controlled study during the birch pollen season in 1989. After a 2-week run-in period, the participants received treatment with budesonide (200 micrograms per nasal cavity and day) or placebo. The patients kept a diary to record their daily nasal symptoms (itching, sneezing, nasal blockage, and secretion). The amount of birch pollen in the air was determined with the aid of a Burkhard pollen trap. A nasal lavage was performed once a week, and the levels of bradykinins and fibrinogen were determined in the lavage fluid samples. The birch pollen season was very mild, resulting in only minor nasal symptoms. In spite of the low pollen exposure, treatment with budesonide reduced the lavage fluid levels of both bradykinins and fibrinogen. The present results show that topical glucocorticosteroid treatment attenuates plasma exudation and the generation of plasma-derived mediators in seasonal allergic rhinitis. This action may not result from simple vascular antipermeability effects of the drug but may rather reflect the anti-inflammatory efficacy of topical glucocorticoids in the airway mucosa.

Administration, Topical↗
PubMed1994

Microvascular exudative hyperresponsiveness in human coronavirus-induced common cold.

BACKGROUND: The inflammatory response of the airway microcirculation in rhinitis and asthma may be recorded as luminal entry of plasma macromolecules (mucosal exudation). This study examines the exudative responsiveness of the subepithelial microvessels in subjects with and without common cold after inoculation with coronavirus. METHODS: The airway mucosa was exposed to exudative concentrations of histamine (40 and 400 micrograms/ml) before and six days after inoculation. To assess whether mucosal penetration of a topically applied agent was altered, nasal absorption of chromium-51 labelled ethylene diamine tetraacetic acid (51Cr-EDTA, MW 372) was also examined. A nasal pool technique kept the challenge and tracer solutes in contact with the same ipsilateral mucosal surface. Concentrations of albumin in lavage fluids were measured as an index of mucosal exudation of plasma. Nasal absorption of 51Cr-EDTA was determined by the cumulated 24 hour urinary excretion of radioactivity. RESULTS: Nine subjects developed common cold after coronavirus inoculation and 10 remained healthy. Histamine produced concentration dependent mucosal exudation of plasma in all subjects before and after coronavirus inoculation. In subjects with common cold, however, the histamine-induced mucosal exudation was significantly augmented compared with the group without common cold. This exudative hyperresponsiveness is not explained by an increased baseline exudation because the lavage regimen used produced comparably low baseline exudation in both groups of subjects, nor is it explained by an increased penetration of topical histamine because the ability of the nasal mucosa to absorb 51Cr-EDTA was not significantly increased in the subjects with common cold. CONCLUSIONS: An increased proclivity of the airway subepithelial microcirculation to respond with plasma exudation develops during coronavirus-induced common cold. This specific exudative hyperresponsiveness may be a feature of inflammatory airway diseases.

Adult↗
PubMed1994

Mucosal nitric oxide may tonically suppress airways plasma exudation.

In a search for airway epithelial mechanisms that may affect the subepithelial microcirculation, we examined plasma exudation responses to NG-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. L-NAME was applied topically on the tracheal mucosa of guinea pigs that had previously received 125I-albumin and/or colloidal gold particles (5 nm) intravenously. Luminal entry of plasma was determined by the levels of 125I-albumin in tracheal lavage fluid. Topical L-NAME (2.2, 9, and 22 mumol), but not intravenous L-NAME (375 mumol/kg), produced plasma exudation into the airway lumen (p < 0.01 to p < 0.001). The L-NAME enantiomer NG-nitro-D-arginine-methyl ester (D-NAME, 9 mumol) produced no exudative response. Coadministration of L-arginine (27 mumol) abolished the L-NAME-induced exudation. The extravasated plasma was distributed in the lamina propria and between epithelial cells (colloidal gold). The epithelial surface structure (scanning electron microscopy) appeared intact. Staining with nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase suggested that epithelial basal may contain nitric oxide synthases. We suggest that endogenously released nitric oxide from epithelial or other superficial cells tonically suppresses the macromolecular permeability of the subepithelial microcirculation.

Animals↗
PubMed1994

Glucocorticoids may not inhibit plasma exudation by direct vascular antipermeability effects in human airways.

In animal airways, single topical treatment with glucocorticoids produces a prompt vascular anti-permeability effect that may last for several hours. This has been considered a potentially important anti-inflammatory action in human airways. The present study, involving nine healthy subjects, examines whether nasal budesonide application affects histamine-induced mucosal exudation of plasma and plasma-derived mediators in human airways. A selected low concentration (40 micrograms.ml-1) of the vascular permeability-inducing agent histamine was kept in one of the nasal cavities for 10 min, and this challenge was repeated at 50 min intervals over 4 h. Ten minutes after the first histamine-challenge, a clinical dose of budesonide (100 micrograms) was sprayed into the same nasal cavity. Nasal lavage fluid levels of albumin and fibrinogen were measured as indices of mucosal exudation of bulk plasma, and bradykinins were analysed to indicate generation of plasma-derived mediators. The baseline levels of albumin and fibrinogen were evaluated in 24 healthy control subjects by means of a 10 min saline lavage. Histamine produced significant mucosal exudation of albumin and fibrinogen, compared to control subjects. Topical budesonide treatment did not affect the histamine-induced mucosal exudation of albumin or fibrinogen, nor did budesonide affect the mucosal output of bradykinins. The present human airway data do not support the view, based on animal findings, that airway glucocorticoids reduce mucosal exudation of plasma by direct vascular effects. We suggest that anti-exudative effects of topical glucocorticoids in airway diseases indirectly reflect the inhibition of cellular inflammatory processes by these drugs, rather than any direct effects on the airway microcirculation.

Administration, Intranasal↗
PubMed1993

The action of beta-receptors on microvascular endothelium or: is airways plasma exudation inhibited by beta-agonists?

The connections between airway inflammation, plasma exudation and a possible anti-exudative action of beta-agonists are discussed. Asthma involves a response to inflammatory mediators which results in increased microvascular leakage with exudation of plasma into the airways. This plasma exudation is a specific inflammatory response and also a general response in the sense that it is independent of the mechanism sustaining the inflammation. Thus, mucosal exudation of plasma may reflect the subepithelial airway inflammatory process, irrespective of its genesis. In addition, the exudate itself contains many substances which may themselves promote inflammation and be major factors in producing and sustaining acute and chronic airway inflammation. This suggests that drug therapies should be aimed at reducing plasma exudation. Studies in guinea pigs have shown that a number of drugs such as xanthines, cromoglycates, glucocorticoids and beta-agonists may inhibit this exudation, but the effect seems to be attenuated in human mucosal tissue. beta-Agonists appear promising in this respect, but if an anti-exudative effect is confirmed for them, it will be necessary to determine whether this is a direct effect or secondary to their effects on cellular inflammatory processes in the airways.

Adrenergic beta-Agonists↗
PubMed1993

Mucosal exudation of plasma is a noninjurious intestinal defense mechanism.

We have demonstrated in sensitized rats that the immediate response to endointestinal challenge with allergen (10(-6) M ovalbumin) is characterized by mucosal exudation of plasma with little or no concomitant change in the mucosal absorption capacity. The luminal entry of plasma macromolecules also leaves the light microscopic structure and the ultrastructure of the mucosa unaffected. It is possible that the plasticity of epithelial zonulae occludens allows a noninjurious and unidirectional paracellular flux of extravasated plasma into the gut lumen. We propose that inflammatory-stimulus-induced mucosal exudation of plasma belongs to the first-line defense mechanisms of the intact lining of the intestine.

Allergens↗
PubMed1993

Plasma exudation and solute absorption across the airway mucosa.

The airway mucosa responds to inflammatory provocations with bulk exudation of plasma into the airway tissue (vascular exudation) and lumen (mucosal exudation). The intensity and time course of the exudative response can be relevantly examined by sampling and analysing airway surface liquids, because the luminal entry of plasma proteins/tracers promptly and quantitatively reflects the exudative response of the airways. The process of mucosal exudation of plasma is a prominent feature of airway inflammation and has been demonstrated in rhinitis, asthma, and bronchitis. Inflammatory mediators and allergen produce mucosal exudation of plasma into the airway lumen (outward permeability) whereas the solute absorption across the mucosa (inward permeability) is unaffected. Hence, in contrast to current views, we have demonstrated that in airway inflammation the solute absorption across the airway mucosa is not increased. The findings suggest the plasma exudation response also as a first line respiratory mucosal defence, allowing potent plasma protein systems to appear on an airway mucosa functionally intact as a barrier toward undue luminal material. Our data on plasma exudation and solute absorption across the mucosa of upper and lower airways further suggest the human nasal airways as a model relevant also for the tracheobronchial airways.

Animals↗
PubMed1993

Effect of seasonal allergic rhinitis on airway mucosal absorption of chromium-51 labelled EDTA.

BACKGROUND: Hyperpermeability of the airway mucosa is thought to be characteristic of allergic rhinitis and asthma. Nine subjects with seasonal rhinitis caused by birch pollen were studied and the nasal mucosal absorption of chromium-51 labelled EDTA was examined both in an asymptomatic period before the season and late into the season when significant allergic rhinitis symptoms were present. METHODS: A nasal pool device was used to keep a concentration of the absorption tracer in contact with a larger part of the mucosa of the ipsilateral nasal cavity. Absorption was allowed for 15 minutes and measured as the radioactivity appearing in the 24 hour urine sample. RESULTS: The nasal absorption of 51Cr-EDTA in subjects with seasonal allergic rhinitis was less during active disease than before the season. CONCLUSIONS: An airway epithelial barrier that is subject to prolonged eosinophilic inflammation may not be disrupted but may rather increase its functional tightness.

Absorption↗
PubMed1993

Effects of nicotine on the human nasal mucosa.

BACKGROUND: Topical application of nicotine and stimulation of tachykinin containing sensory nerves have been shown to produce mucosal exudation of plasma and derangement of the epithelial lining in guinea pig and rat airways. If this occurred in man these effects might contribute to the pathogenesis of airway disease. This study, performed in healthy volunteers without atopy, examined whether nicotine affects the plasma exudation response and the mucosal absorption permeability of the human nasal airway. METHODS: The acute effects of increasing topical doses of nicotine (0.08-2.0 mg) were examined (n = 8) on nasal symptoms (pain), mucosal exudation of plasma (albumin), mucosal secretion of mucin (fucose), and mucosal exudative responsiveness (histamine induced mucosal exudation of albumin). A separate placebo controlled study was carried out to determine whether frequent applications of the high dose of nicotine (2.0 mg given eight times daily for nine days) had any deleterious effects on the airway mucosa detectable as altered responses to histamine challenge. Both mucosal exudation of plasma (n = 12) and mucosal absorption of chromium-51 labelled EDTA (n = 8) were thus examined in nasal airways exposed to both nicotine and histamine. RESULTS: Nicotine caused nasal pain and produced dose dependent mucosal secretion of fucose but failed to produce any mucosal exudation of albumin. The exudative responsiveness to histamine was, indeed, decreased when the challenge was performed immediately after administration of acute doses of nicotine, whereas the responsiveness was unaffected when histamine challenges were carried out during prolonged treatment with nicotine. The nasal mucosal absorption of 51Cr-EDTA in the presence of histamine did not differ between subjects receiving either placebo or nicotine treatment for nine days. CONCLUSIONS: The results indicate that nicotine applied to the human airway mucosa produces pain and secretion of mucin, but inflammatory changes such as mucosal exudation of plasma and epithelial disruption may not be produced. Neurogenic inflammatory responses, which are so readily produced in guinea pig and rat airways, may not occur in human airways.

Absorption↗
PubMed1993

Appearance of airway absorption and exudation tracers in guinea pig tracheobronchial lymph nodes.

This study examines the fate of extravasated plasma in inflammatory stimulus-challenged large tracheobronchial airways of ketamine-xylazine-anesthetized guinea pigs. Entry of plasma tracers into the airway lumen was determined by a validated noninjurious airway lavage technique. Removal by airway lymphatics was assessed by tracheobronchial lymph node levels of plasma tracers. Mucosal challenges with histamine (5 nmol), bradykinin (5 nmol), capsaicin (0.4 nmol), or allergen (ovalbumin, 3 pmol) increased the appearance of a plasma tracer (131I-labeled albumin previously injected intravenously) in the airway lumen within 10 min (10-20 times control; P < 0.001), whereas the contractile agent carbachol (8 nmol) was without exudative effect. The mediators were without effect, and capsaicin and allergen only slightly increased the lymph node level of plasma exudation tracer (1.5 times control; P < 0.05). Hence, removal via the lymphatic route of plasma macromolecules may be negligible in the acute and postacute phases of an airway exudation response. Experiments were also carried out with luminally applied macromolecular tracers. These were absorbed from the mucosal surface into the circulation, but a small portion was also transported to the lymph nodes, demonstrating the interconnections between the mucosa and the sampled nodes. Only capsaicin produced an increased node level of absorption tracer. Immunohistochemistry showed that the tracheobronchial tissue and lymph nodes are endowed with nerve fibers containing substance P, the release of which may have mediated lymph transport, vascular, and exudative effects of capsaicin in the present studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1993

Allergen-induced biphasic plasma exudation responses in guinea pig large airways.

In this study involving sensitized guinea pigs (anesthetized intramuscularly with a 3:2 mixture of ketamine+xylazine, 1 ml/kg), we applied allergen (ovalbumin) selectively to the tracheobronchial mucosa (sparing the nasal passages and the terminal airways) and examined the occurrence of immediate and late-phase inflammatory exudation of plasma and plasma-derived mediators (bradykinins) into the airway lumen. The experiments were terminated 10 to 480 min after challenge. A selective lavage that sampled the surface liquids of the extrapulmonary bronchi and the lower trachea was performed. The amount of plasma (microliter) was determined by analysis of a plasma tracer, [125I]albumin, in lavage fluid and blood (plasma) samples. Ovalbumin, 3 to 12 pmol, and histamine, 5 and 10 nmol, produced a dose-dependent immediate exudation response (p < 0.001). The effects were nonneurogenic because they were not affected by topical lidocaine given in a dose (3 nmol) that prevented the exudative effect of capsaicin. The 6- and 12-pmol doses of ovalbumin (but not 3 pmol) produced a significant late-phase exudative response at 5 h (p < 0.001), and both the immediate and late phases were associated with increased (p < 0.01 to p < 0.001) levels of bradykinin in the lavage fluids. Histamine, even in doses that produced a greater early response than the allergen, did not produce a late-phase response. A single topical dose of an antiasthma steroid (budesonide, 12 mumol/kg) administered just before ovalbumin (6 pmol) had little effect on the immediate response but inhibited the late-phase response (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1993

Mucosal exudation of fibrinogen in coronavirus-induced common colds.

We studied the mucosal exudation of plasma in relation to pathophysiological events during an induced common cold. Coronavirus 229E was inoculated nasally in 20 healthy volunteers under controlled conditions. Ten volunteers developed the common cold, determined by symptom scores and serology. The bulk plasma exudate was monitored, using fibrinogen (MW 340 kD) in nasal lavage fluids as an endogenous marker. Following inoculation, anterior rhinoscopy and objective registrations of nasal mucosal temperature, nasal discharge weight, and nasal blockage index by peak expiratory air flow, were followed twice daily for 6 days. Mucosal plasma exudation, as assessed by fibrinogen in lavage fluids, increased hundredfold after virus inoculation, concomitantly with the subjective symptoms and objective physiological changes. We propose that this exudation reflects the degree of subepithelial inflammation, and suggests that plasma bulk exudate, including all potent plasma protein systems may be involved in the resolution of acute viral rhinitis--common cold.

Adult↗
PubMed1992

Increased sensitivity to toluene diisocyanate (TDI) in airways previously exposed to low doses of TDI.

Repeated airway exposures to toluene diisocyanate (TDI) may cause sensitization and asthma. This study has examined the acute inflammatory response to TDI in guinea-pig tracheobronchial airways, the development of increased sensitivity to TDI and the effects of xanthines and a glucocorticoid on these responses to TDI. A restricted surface area of the tracheobronchial mucosa of Ketalar-Xylazin anaesthetized guinea-pigs was exposed to TDI, dissolved in olive oil, by means of 1 min infusions through an oral catheter. The TDI-induced inflammatory process was quantified by determination of airway luminal entry of plasma. Already 3 nl (approximately 20 pmol) of TDI produced a significant and sustained exudation response (P less than 0.001 to P less than 0.01, 5 and 17 hr after exposure). Pretreatment with intravenous enprofylline (25 mumol/kg) intraperitoneally or 26 mumol/kg by tracheal superfusion) was without effect. Two repeated exposures to TDI 3 nl (on days 1 and 8) made the animals hyperresponsive to TDI so that on day 15 a previously subthreshold dose of TDI (0.3 nl) produced significant exudation both at 5 and 17 hr after exposure (P less than 0.001 to P less than 0.01). Similarly, two repeated dermal exposures to a large dose of TDI (20 microliters) lowered the threshold for tracheal provocation with TDI. Budesonide (2.6 mumol/kg orally) given daily during the topical airway 'sensitization' regimen (days 1-14) significantly reduced the response to the subsequent 0.3 nl challenge dose of TDI (P less than 0.05). The effects of daily treatments with either theophylline (100 mumol/kg) or enprofylline (50 mumol/kg) were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1992

Topical vasoconstrictor (oxymetazoline) does not affect histamine-induced mucosal exudation of plasma in human nasal airways.

Mucosal exudation of almost unfiltered plasma proteins, plasma-derived mediators and fluid has recently been advanced as a major respiratory defence mechanism. Oxymetazoline chloride is a commonly used decongestant agent. By reducing blood flow it may reduce mucosal exudation and thus compromise the mucosal defence capacity. This study examines the effect of topically applied oxymetazoline on histamine-induced plasma exudation into human nasal airways. Twelve normal volunteers participated in a double-blind, randomized, cross-over and placebo-controlled study with pretreatment with a single dose oxymetazoline chloride (5 micrograms or 50 micrograms; a dose previously known to reduce nasal mucosal blood flow by almost 50%) prior to the histamine challenge sequence. Nasal lavages were performed every 10 min for 140 min, and three histamine challenges were performed at 30-min intervals during this period. The concentrations of two exudative indices, N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity and albumin, were measured in the nasal lavage fluids. Nasal symptoms (sneezing, nasal secretion and blockage) were assessed by a scoring technique. Histamine induced all three symptoms with correlatively raised levels of the biochemical markers for plasma exudation. Oxymetazoline chloride caused a significant decrease in nasal stuffiness, but did not influence the other nasal symptoms or the histamine-induced plasma exudation. It is concluded that histamine-induced plasma exudation is not influenced by topical oxymetazoline. Thus, an important airway defence reaction such as plasma exudation may be little affected by topical alpha-adrenoreceptor-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗