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Biomedical subjects

C G Persson

Publications and source records attributed to C G Persson.

At least 127 records · Page 7Linked to original sources
PubMed1991

Airway plasma exudation in detection of antiasthma drugs.

Increased numbers of cells and levels of cellular mediators in the airways may be without consequence or reflect tissue repair and can, therefore, not be equated with inflammation. Many tissue responses to inflammation are non-specific in that they are only exaggerations of base-line functions (blood flow, secretion, tone etc) which are stimulated also by non-inflammatory influences. In contrast, when there is plasma exudation in the airways this is a specific defence/inflammatory response. Accordingly, plasma exudation is not an increase in the normal capillary exchange of solutes but a dramatic increase in venular permeability. Plasma exudation is a graded response to mucosal inflammatory provocations and it is well correlated to symptoms in airway disease. The plasma exudate always crosses the epithelial lining to enter the airway lumen. Indeed, exudative indices in samples of airway surface liquids faithfully reflect intensity and time course of inflammatory processes in the underlying airway tissue. Drugs will reduce the exudation by any action that is a significant antiinflammatory effect, be it on recruitment/activation of cells on formation/release/action of mediators or directly on the permeability-regulating endothelial cells in the venular wall. The notion that plasma exudation is a significant pathogenetic mechanism in its own right in asthma does not reduce its instrumentality in the detection of new drugs to combat this disease.

Animals↗
PubMed1991

Plasma exudation in the airways: mechanisms and function.

Inflammatory challenges of tracheobronchial and nasal mucosa produce prompt extravasation or exudation of plasma from the well developed microcirculation just beneath the epithelial base. Plasma exudation is not an exaggeration of the normal capilliary exchange of fluid and solutes but a specific inflammatory response of post-capilliary venules. The exuded plasma may not produce oedema. By a rapid, undirectional, unfiltered and yet non-injurious process, plasma exudates cross the mucosal lining to appear on the airway surface at the site of challenge. In vitro data suggests the possibility that a slightly increased hydrostatic pressure moves the acellular exudate through valve-like openings between epithelial cells. By the venular-mucosal exudation mechanism all the potent protein systems of circulating plasma will operate in respiratory defence on the surface of an intact mucosa. A further inference is that exudative indices obtained from the airway surface quantitatively reflect the intensity and time course of mucosal/submucosal inflammatory processes. Irrespective of which particular cellular mechanism happens to fuel the inflammation. Mucosal exudation of plasma characteristically occurs in health and disease also when there is no airway oedema, no epithelial disruption, and no increased absorbtion ability. However, exuded plasma and its derived peptide mediators potentially contribute to several pathophysical and pathophysiological characteristics of inflammatory airway diseases.

Animals↗
PubMed1990

Exudative indices in airways inflammation.

Airways inflammation has come to be equated with the presence of inflammatory cells and their products in airway lumen and tissue. However, the inflammatory condition must also, or rather, be determined by indices which show to what degree the tissue itself is affected by the process. Plasma exudation from abundant subepithelial microvessels is a specific defence/inflammatory tissue response to mucosal provocations; promptly after extravasation, the plasma exudate reversibly and non-injuriously creates intercellular pathways across the mucosa; the exudate enters the airway lumen without compromising the epithelial lining as a barrier to luminal solutes; there is a good correlation between surface and tissue plasma exudates. I propose that plasma tracers on the mucosal surface can identify the ongoing airway inflammation, its intensity and time-course in great detail.

Exudates and Transudates↗
PubMed1990

Albumin, bradykinins, and eosinophil cationic protein on the nasal mucosal surface in patients with hay fever during natural allergen exposure.

This study examined plasma- and eosinophil-derived products in nasal lavage fluids obtained from patients with hay fever during natural allergen exposure. Nine patients with strictly seasonal allergic rhinitis and five normal, nonallergic subjects (control group) were studied. Nasal lavages were performed twice weekly, starting 1 week before the expected birch-pollen season and continuing for 6 weeks, thereby covering the entire birch-pollen season. Nasal symptoms and pollen counts were recorded daily. The lavage fluid was analyzed for it content of albumin, bradykinins, and eosinophil cationic protein (ECP). During the pollen season, each of these solutes was significantly increased in the nasal lavage fluid from the allergic patients (p less than 0.05) but not from the control subjects. Albumin, bradykinins, and ECP generally correlated better between themselves than with symptoms and pollen counts. We conclude that natural exposure to allergens induces plasma exudation and increased levels of ECP on the human nasal mucosa.

Adolescent↗
PubMed1990

On the use of absorbing discs to sample mucosal surface liquids.

A common technique to sample airway mucosal 'surface' liquids is with absorbing discs of filter paper. The present study examined the efficacy of this technique by analysing tracheal liquids of control and capsaicin (0.1 nmol)-exposed guinea-pig airways. Mucosal fluids, obtained by topically applied discs or by a specific lavage procedure, and tracheal tissue were sampled. The animals had received FITC-dextran (MW 70 kDa) intravenously and this specific plasma tracer was analysed in the sampled material. Under control conditions significantly more FITC-dextran was found in the discs than in the tracheal lavage fluids (P less than 0.001) despite the fact that the lavaged mucosal surface was much larger than that covered by the discs. Capsaicin significantly increased the content of FITC-dextran in all fluids sampled as well as in the airway tissue. In all cases concentrations of FITC-dextran in the disc fluids did not differ much from that in the tissue samples. These data suggest that absorbing discs severely disturb the epithelial-barrier function and sample subepithelial fluid and solutes including macromolecules. As demonstrated in this study by the elevated content of a plasma tracer molecule an inflammatory process may, nevertheless, be traced in the mixture of surface and tissue fluids that is sampled by the discs.

Absorption↗
PubMed1990

The 'nasal pool' device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions.

A 'nasal pool' (NP) device, a compressible plastic container with an adapted nozzle, was used to perform a continuous 10-min nasal provocation and lavage. This novel technique brings known concentrations of agents into contact with a large and defined area of the nasal mucosal surface for extended periods of time. Simultaneously, the surface exudations/secretions of the same nasal mucosa are effectively sampled by the NP fluid. A concentration-response study of histamine (80, 400 and 2000 micrograms/ml) was performed in 12 normal subjects on three different occasions. Exudation of plasma albumin into the lavage fluid was measured to quantitate the histamine-induced airway inflammation. The effect of the dwell time on exudation was examined using histamine (400 micrograms/ml) instilled in the nasal cavity for time periods from 10 sec to 10 min. The time course of histamine-induced plasma exudation response was studied by exposing the mucosa to histamine (400 micrograms/ml) for 12 min, with the NP renewed every minute. Allergen-provocations were performed in subjects with hay fever and TAME-esterase activity in the returned lavage fluid was determined to indicate the degree of response. Histamine produced a concentration-dependent increase in albumin levels in the NP fluid; 123.3 +/- 25.6, 213.8 +/- 19.7 and 430.2 +/- 32.0 micrograms/ml (mean +/- s.e.m.), respectively. The time-course study demonstrated that plasma exudation into the lumen occurred promptly and that the exudation response reached a maximum after exposure to histamine for 6-10 min. The dwell-time experiments supported this finding. After 10 min the exudation appeared to decline despite the continued presence of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Albumin protects against capsaicin- and adenosine-induced bronchoconstriction and reduces overflow of calcitonin gene-related peptide from guinea-pig lung.

In the guinea-pig isolated, perfused lung, the effect of albumin on oedema formation and bronchoconstriction as well as on capsaicin-induced overflow of calcitonin gene-related peptide-like (CGRP-LI) immunoreactivity has been examined. CGRP was used as an indicator of sensory nerve activation since it is more stable than the tachykinins substance P and neurokinin A. As expected, the lung water content was significantly (P less than 0.001) higher in lungs perfused with albumin-free buffer than when the buffer contained 4.5% albumin. Also, in albumin-free buffer the baseline airway resistance (RL) was increased and dynamic compliance (CDYN) reduced (P less than 0.001). Capsaicin (1 x 10(-6) M) was about 100 times less potent as a bronchoconstrictor when preincubated with albumin for 45 min, and the associated overflow of CGRP-LI was inhibited (from 221.0 +/- 63.4 fmol to 8 fmol fraction-1). When CGRP (50-200 pM) was incubated for 60 min with albumin, the recovery of CGRP-LI was 48% lower (P less than 0.01) than in the absence of albumin, corresponding to a loss rate of about 1% min-1. Catabolism or binding of neuropeptides can therefore hardly explain the diminished bronchoconstrictor potency of capsaicin. Capsaicin was also less effective as a constrictor in isolated bronchi after preincubation with albumin, suggesting that capsaicin itself may be bound or absorbed to this macromolecule. The bronchoconstrictor response to adenosine was also diminished in the presence of albumin. Adenosine was about 1000 times less potent as a bronchoconstrictor if dissolved in albumin 45 min before infusion, but only 10 times less potent when administered as bolus doses to albumin buffer-perfused lungs. Metabolism of adenosine may be the reason for the decreased potency of adenosine. The enzymatic activity may have been associated with impurities in the albumin preparation used (bovine serum albumin fraction V is greater than or equal to 96% pure) or contained in the protein itself. Since the bronchoconstrictor effect of acetylcholine was not reduced in the presence of albumin, it is not likely that albumin affects directly the contractility of the smooth muscle. These data demonstrate the importance of studying the influence of albumin on the in-vitro actions of pharmacological agents. The absence or presence of albumin products in nutrient buffer solutions may mean dramatic differences in potencies of certain drugs. Furthermore, bolus injections of agents are preferable, and preincubation together with albumin should be avoided.

Adenosine↗
PubMed1990

Clearance of 99mTc DTPA from guinea pig nasal, tracheobronchial, and bronchoalveolar airways.

Technetium-99m labelled diethylenetriamine penta-acetate (99mTc-DTPA) was used to compare small solute absorption (clearance) from nasal, tracheobronchial, and bronchoalveolar airways in anaesthetised guinea pigs. 99mTc DTPA dissolved in saline was superfused through nasal and orolaryngeal catheters on to nasal and tracheobronchial airways; a small particle aerosol of nebulised 99mTc DTPA was delivered to the bronchoalveolar airways through a tracheostomy. Radioactivity over the appropriate region was then determined with a gamma camera. Mucociliary transport of 99mTc DTPA appeared not to contribute to the disappearance of 99mTc DTPA. Time-activity curves were obtained and half life values calculated by fitting a monoexponential equation to the experimental data. A progressive reduction in 99mTc DTPA was recorded from the nasal and tracheobronchial airways and from the bronchoalveolar airway, suggesting that absorption was occurring. The disappearance of 99mTc DTPA was fastest from the bronchoalveolar region, which also had the largest mucosal surface. The similar shape of the retention curves for the nasal and tracheobronchial regions suggests that the characteristics of nasal absorption of 99mTc DTPA could prove applicable to the tracheobronchial region. It is proposed that the present methods are suited for comparing the pharmacology of small solute absorption across nasal, tracheobronchial, and bronchoalveolar airway mucosa.

Absorption↗
PubMed1990

Capsaicin-induced bronchoconstriction and neuropeptide release in guinea pig perfused lungs.

In the guinea pig isolated perfused lung, we have examined the relationship between the effects of capsaicin and neuropeptide release and the possible existence of an axon reflex arrangement. Bolus injections into the pulmonary artery of capsaicin (1-100 pmol), substance P (10-1,000 pmol), and neurokinin (NK) A (10-100 pmol) produced a concentration-dependent bronchoconstriction, whereas calcitonin gene-related peptide (CGRP, 20-40 nmol) was without effect. Repeated administration of capsaicin at 40- to 60-min intervals was not associated with tachyphylaxis. These data support the presence of a NK2- (or NKA) type of tachykinin receptor in the guinea pig airways. Tetrodotoxin (0.3-3 microM) inhibited the effect of capsaicin, indicating that an axon reflex was operant. Capsaicin increased overflow of CGRP-like immunoreactivity (-LI) and NKA-LI, the latter only during concurrent infusion of the enkephalinase inhibitor phosphoramidon (3 microM). Phosphoramidon also increased overflow of CGRP-LI, suggesting that both NKA and CGRP were catabolized by a similar enzyme. The purine nucleoside adenosine did not cause any detectable overflow of CGRP-LI, indicating that neuropeptides may not be involved in adenosine-evoked bronchoconstriction and that bronchoconstriction per se does not induce neuropeptide overflow. Capsaicin and NKA had only minor effects on buffer flow, whereas substance P produced pulmonary vasoconstriction. These data clearly demonstrate that capsaicin acts via an axon reflex in the guinea pig airways. Supramaximal concentrations of capsaicin are needed to detect neuropeptide overflow, but the possibility exists that released neuropeptides mediate its effects.

Acetylcholine↗
PubMed1990

The airway epithelial lining in guinea pigs is intact promptly after the mucosal crossing of a large amount of plasma exudate.

In the present study of anaesthetized guinea pigs, we have confirmed by chemical analyses that 10 min after topical mucosal provocation with capsaicin 0.4 nmol of platelet-activating factor 8 nmol plasma macromolecular tracers (FITC-dextran, molecular weight 156 kD, previously injected intravenously) have been significantly exuded into airway tissue and lumen. We have also examined the airway mucosa and the mucosal surface material using fluorescence, light, and electron microscopy. Thus we have demonstrated by histological techniques that promptly after the induction of large exudative responses plasma macromolecules are abundant in the lumen as well as in the lamina propria. Furthermore, the exudate is seen on the surface of a mucosa that has an intact epithelial lining. These observations are evidence in favour of the possibility that plasma exudation into the lumen is a first-line defense mechanism of the normal airway mucosa.

Animals↗
PubMed1990

Subepithelial hydrostatic pressure may regulate plasma exudation across the mucosa.

This study demonstrated in guinea pig tracheal tubes in vitro that small increases in serosal hydrostatic pressure caused significant mucosal crossing of serosal macromolecules. Reversibility and repeatability of this passage agree with inflammatory stimulus-induced appearance of exuded plasma in airway lumen in vivo. Bradykinin, histamine, and terbutaline, which induce and inhibit, respectively, plasma exudation in vivo, were without effect on the present in vitro permeability. Carbachol, similar to histamine, contracted the trachea, and did not increase, but rather decreased the pressure-induced luminal entry of serosal macromolecules. It is proposed that a plasma-exudation-induced hydrostatic pressure load transiently separates epithelial cells, providing a direction-selective and non-injurious intercellular pathway for passage of bulk plasma exudate into the airway lumen. This mechanism would allow potent plasma protein systems to operate on mucosal surfaces at sites of insults without compromising the mucosa as a barrier to luminal solutes.

Animals↗
PubMed1990

Glucocorticoids.

Explore the source record for details and available documents.

Administration, Topical↗
PubMed1990

Rapid clearance of xanthines from airway and pulmonary tissues.

The airway and pulmonary fate of two antiasthma xanthines was examined in a guinea pig perfused lung preparation where the airway mechanics and airway microvascular perfusion are maintained at near normal values. 14C-theophylline or 14C-enprofylline was infused for 10, 30, and 300 s into the pulmonary artery of the guinea pig isolated lung. The radioactivity increased rapidly (within 10 s) in tracheobronchial as well as in lung tissue, confirming that the large airway microcirculation was well supplied also by the perfusion. The effluent concentrations of total 3H and 14C radioactivity at the onset, during, and after intrapulmonary infusion of 14C-labeled xanthines and 3H-sucrose were closely associated, suggesting that the xanthines, like sucrose, largely distributed in extracellular fluid and were not taken up by the tissues. No metabolites of enprofylline or theophylline could be detected in the lung tissue or lung effluent, suggesting that xanthines are not biotransformed by the guinea pig lung. After intratracheal instillation of 14C-theophylline, the peak radioactivity in the lung effluent appeared in the second 15-s fraction after instillation, and after 10 and 60 min, 68.1 +/- 4.7% and 86.9 +/- 8.4%, respectively, of the given dose had appeared in the lung effluent. The present data suggest a mainly extracellular distribution and a rapid clearance of xanthines from the lung and airway tissues. The rapid disappearance of topical theophylline may explain the lack of success of inhalation therapy with this drug.

Animals↗
PubMed1990

Plasma exudation in tracheobronchial and nasal airways: a mucosal defence mechanism becomes pathogenic in asthma and rhinitis.

Plasma exudation into airway tissue and lumen is a defence and inflammatory reaction. If exaggerated it may become pathogenic as in asthma and rhinitis. Exuded plasma contains an abundance of mediators (kinins, complement fragments, fibrinolysis- and coagulation-peptides etc.) which have direct inflammatory and obstructive actions and which can attract, prime, and activate inflammatory cells. The plasma exudate may cause airway hyperresponsiveness by increasing mucosal thickness. In the lumen the exuded plasma is added to irritant and viscous secretions and plugs. Antiasthma and antirhinitic drugs, including glucocorticoids, disodium cromoglycate, beta-adrenoceptor agonists and xanthines, have anti-exudative actions that may include a direct reduction of vascular permeability and other anti-inflammatory effects. Recent data with nasal and tracheobronchial airways in guinea-pigs and humans suggest that plasma can pass into the airway lumen without disturbing the integrity of the epithelial lining as a barrier to inhaled molecules. Potent proteins from circulating plasma can, thus, promptly appear on the surface of a normal mucosa to neutralize offending materials. It is proposed that plasma exudation must be considered a first line mucosal defence system along with mucociliary transport in the airways.

Animals↗
PubMed1990

Airway opioid receptors mediate inhibition of cough and reflex bronchoconstriction in guinea pigs.

Effects of opioids and opioid antagonists on citric acid-induced cough and reflex bronchoconstriction have been examined in conscious guinea pigs. Airway reflexes produced by inhaled citric acid are mediated by capsaicin sensitive sensory neurons, and we examined particularly the possibility that inhibitory effects of opioids can be exerted locally in the airway. As expected, systemically administered codeine (1-10 mg/kg), meperidine (3-30 mg/kg) and morphine (1-10 mg/kg) dose-dependently inhibited cough and bronchoconstriction. However, inhalations of nebulized codeine (10-100 mg/ml) and morphine (10-30 mg/ml) also produced these effects. The potency and rapid onset of action of inhaled codeine suggest that it exerted its effects without first being metabolized to morphine. The opioid receptor antagonist naloxone completely (10-100 micrograms/kg), and nalorphine (a mixed agonist/antagonist) (1-3 mg/kg) partly, inhibited codeine's antitussive and antibronchoconstrictor effects. Nalorphine alone (3-30 mg/kg) inhibited citric acid induced reflexes, whereas naloxone was without effect. Prior inhalation of a quaternary opioid receptor antagonist, levallorphan methyl iodide (10 mg/ml), abolished the inhibitory effects of inhaled codeine (30 mg/ml). The present data suggest that inhibition of cough and reflex bronchoconstriction can be produced by opioids, acting on mu and kappa receptors located in the guinea pig tracheobronchial tree. The possible existence in the airways of a unique opioid receptor mediating inhibition of cough (as described in the central nervous system) cannot be excluded.

Animals↗
PubMed1990

Comparison between theophylline and an adenosine non-blocking xanthine in acute asthma.

Enprofylline, a drug without adenosine antagonism and theophylline, a potent adenosine antagonist, were compared, double-blind, randomized, in acute asthma (n = 33). The drugs were given intravenously as loading over 10 min followed by maintenance infusion for 24 h. Mean final plasma levels were very high with enprofylline (14 mg.l), and larger than calculated with theophylline (16 mg.l). Seven patients had maximum levels of enprofylline ranging between 16 and 42 mg.l. Extreme plasma levels of enprofylline were not associated with any theophylline-like central nervous system excitatory effects related to seizure-inducing ability. Some irregularities in the heart rhythm did not raise clinical problems and no significant difference between enprofylline and theophylline was recorded. At 1 h patients on enprofylline (mean plasma level: 5.7 mg.l) and theophylline (12.2 mg.l) had improved their peak expiratory flow rates by 31% and 15% (p less than 0.05), respectively. The improvement in lung function after 24 hours did not differ between treatments suggesting that the high levels of enprofylline were supramaximal for its anti-asthma effects in this situation. In conclusion, with enprofylline it is demonstrated that an adenosine non-blocking xanthine derivative may lack CNS-excitatory effects, but be more potent than theophylline in the treatment of acute asthma.

Acute Disease↗
PubMed1990

Early and late tracheobronchial plasma exudation by platelet-activating factor administered to the airway mucosal surface in guinea pigs: effects of WEB 2086 and enprofylline.

The effects of the platelet-activating factor (PAF) antagonist, WEB 2086, and the xanthine, enprofylline, on PAF-induced plasma exudation in tracheobronchial airways has been studied in guinea pigs. Superfusion of PAF (4 nmol) onto the tracheal mucosal surface caused a significant exudation of the i.v. plasma tracers [131I]albumin and fluorescein isothiocyanate-dextran (fluorescein-labeled dextran MW 156 kDa) during the first 15 min after PAF (early response) and also 5 hr later (late response). The early, but not the late, response could be identified histologically by a particulate tracer (carbon given i.v.) which was trapped in submucosal leaky vessels. WEB 2086 [3 mg (6.6 mumol)/kg] caused significant attenuation of both the early plasma exudative response (with loss of carbon-labeled vessels) and the late plasma exudative response to PAF. The late response was equally well attenuated by enprofylline [4.85 mg (25 mumol)/kg] given before PAF. It is concluded that PAF-induced late (as well as early) plasma exudative responses in guinea pig tracheobronchial airways are the result of specific receptor activation by topical PAF and that the antiasthma xanthine enprofylline can inhibit this PAF-induced late response. Our data suggest that particulate tracers, such as carbon, cannot detect microvessels involved in the ongoing late phase exudative response to PAF.

Animals↗