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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 35 (1988), S. 231-235 
    ISSN: 1432-1041
    Keywords: allergic rhinitis ; platelet activating factor ; nasal expiratory peak flow rate ; nasal hyperreactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Platelet activating factor (PAF) is known to have a wide range of biological activities. In the lower airways PAF has been suggested as the biochemical mediator partly responsible for the bronchial hyperreactivity which is a feature of asthma. In order to study whether PAF has a similar effect in the upper airways, we carried out a double blind, placebo-controlled cross-over study in twelve patients with strictly seasonal allergic rhinitis. The study was performed in pollen-free winter months. 26 µg PAF or placebo was sprayed into each nasal cavity 8 h and 1 h before a nasal allergen challenge. The nasal response to PAF and the allergen challenge that followed was monitored by repeated measurements of nasal expiratory peak flow rate and symptom scores. PAF induced only minor changes in nasal patency and nasal symptoms as compared to placebo. However, pretreatment with PAF induced an increase in responsiveness of the nasal vasculature to the allergen challenge that followed. This was registered as a small, but statistically significant increase in the symptom scores for nasal blockage, from 1.7 (0.3; SEM) after placebo pretreatment to 2.4 (0.36; SEM) after PAF (p〈0.05). A similar trend was also noted for the measurements of nasal peak flow. The other response parameters, sneezes and secretion, remained identical. These results suggest that PAF may play a role in human nasal hyperreactivity, but it appears that PAF is not a major mediator involved in the induction of this phenomenon.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 625-627 
    ISSN: 1432-1041
    Keywords: beclomethasone dipropionate ; rhinitis ; allergy ; benzalkonium chloride ; hay fever ; mucociliary clearance ; saccharine test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The local effect of an aqueous suspension of beclomethasone dipropionate on human nasal mucociliary clearance was studied in 14 healthy volunteers. A triple blind, randomized, placebo controlled, cross-over design was utilised. Measurements of mucociliary clearance were made before treatment, after a single dose and after one week of continuous treatment either with placebo or active substance, utilising the saccharine-dye test. No change in mucociliary clearance was found after treatment with beclomethasone dipropionate or placebo suspension.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Nasal airways ; Plasma exudation ; Xanthine derivatives ; fibrinogen ; bradykinins ; terbutaline ; theophylline ; nasal mucosa ; nasal lavage ; histamine provocation test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Experimental data suggest the possibility that common bronchodilators, such as the xanthines and β2-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 differentsized 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 IV 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 β2-adrenoceptor agonists, at clinically employed plasma levels, may not affect the microvascular (and epithelial) exudative permeability and the bradykinin forming capacity of human airways.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 371-373 
    ISSN: 1432-1041
    Keywords: disodium chromoglycate ; nasal airway resistance ; platelet activating factor ; healthy volunteers ; rhinomanometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirteen healthy subjects participated in a double blind, randomized, cross-over investigation of whether or not intranasal disodium chromoglycate could block the change in nasal airway resistance induced by platelet activating factor (PAF). Placebo or active drug was given for 3 days before intranasal challenge with PAF. Nasal airway resistance before and at intervals after callenge was determined with a rhinomanometer. Pretreatment with disodium chromoglycate blocked the decrease in nasal airway resistance induced by PAF. This indicates an alternative mode of action of disodium chromoglycate in the treatment of allergic airway diseases.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 355-357 
    ISSN: 1432-1041
    Keywords: substance P ; mucociliary activity ; inflamatory reactions ; nose ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Substance P (SP), a potent inflammatory agent, has been found in sensory nerve fibres in the nasal mucosa in several experimental animals as well as in man. It may participate in the inflammatory response as part of the mucosal defence against foreign materials. In experimental animals SP has been found to increase mucociliary in airway mucosa. The present study was performed in order to find out the relationship between topically applied SP and nasal mucociliary function in humans. Thirteen healthy volunteers were challenged with 65 µg SP or placebo in a randomized cross over fashion and mucociliary transport time was determined each time using the saccharine dye test. The dose of SP was chosen after an open dose-response study. No statistically significant change in the mucociliary transport time was found after challenge with SP as compared to placebo. The possible reasons for this are discussed.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 20 (1990), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Various mediator systems have been stressed as important in the generation of the signs and symptoms of allergic disease such as hay fever. Nevertheless, in the upper airways, histamine is still the only mediator which behaves consistently in terms of release at appropriate challenge, produces all the major symptoms of rhinitis at a local challenge, and the specific antagonist influences the signs and symptoms of rhinitis in the challenge situation as well as during natural allergen exposure. Although the majority of hay fever symptoms are influenced by H1-receptors, there are exceptions. An important one is the symptom of nasal blockage, which is due to tissue oedema and a decrease in the tone of the capacitance vessels. Another point to be stressed is that histamine alone does not induce any protracted mucosal inflammatory response with associated symptoms, influx of eosinophils and increase in responsiveness that is associated with the exposure to allergen. Nevertheless, from a clinical point of view, antihistamines are still valuable pharmacological agents for the clinical management of hay fever symptoms.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 21 (1991), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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 μg or 50 μg; 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 α-adrenoreceptor-mediated vasoconstriction. It is further suggested that the antiblockage effect of oxymetazoline can be utilized in nasal research without interfering with the exudative indices which appear on the mucosal surface as a quantitative reflection of the airway tisue involvement in inflammatory processes.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 21 (1991), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Blood flow was determined in weal and flare reactions and in late dermal reactions after skin-prick tests with allergen, histamine, bradykinin and compound 48/80 in pollenallergic subjects. Local blood flow was measured with laser Doppler flowmetry intermittently for up to48 hr at three distances from the prick centre (2 mm; weal, 15mm; flare and 30 mm). Continuous recordings were also made in the weal area after challenge with bradykinn and compound 48/80. The size of the induced weal and flare area of all the substances and the late phase after allergen was determined using digitized planimetry. Furthermore, simultaneous determinations of local dermal temperature and blood flow in the weal and flare site were performed intermittently for 6 hr after allergen and histamine challenges. There was a dose-dependent and distance-related increase in blood flow for all the substances tested. The blood flow in the 2-mm registrations had normalized 20 min after bradykinin, 1.5–2 hr after histamine and 3 hr after compound 48/80, while allergen induced a continuous increase in blood flow for more than 24 hr. The area of the weal and flare reaction was dose related for all substances, and a similar dose-dependent increase was noted for the observed dermal late-phase reactions present after allergen. The local temperature after challenge with allergen and hislamine was also increased in a distance-dependent manner. These studies suggest that laser Doppler flowmetry is a sensitive and reproducible method to quantify blood flow changes occurring after skin-prick tests. Different putative mediators or mast cell stimulating substances produce various response profiles, all of which differ from those observed after allergen. Temperature measurements after skin-prick tests seem to follow the observed changes in blood flow as measured with laser Doppler flowmetry, which may be why both techniques might reflect changes in capillary blood flow.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A great variety of provocations of the airway mucosa produce extravasation of plasma from the abundant subepithelial microvessels. A plasma exudate has important actions through its volume, its specific and unspecific binding proteins, its enzyme systems, and its potent peptides (of kinin. complement, coagulation, fibrinolysis and other systems). If allowed to operate on the surface of an intact mucosa the plasma exudale would have important roles in normal airway defence. Recent observations in guinea-pig tracheo-bronchial airways and in human nasal airways suggest that the mucosal exudation of plasma into the airway lumen is a non-injurious fully reversible process. Threshold exudative responses thus resulted in the appearance of an ‘unfiltered’ plasma exudate not only in the lamina propria but also on the surface of an undisrupted mucosa. Even after extensive luminal entry of exudate the epithelial lining was intact, as judged by light, fluorescence and electron microscopy. Hence, the epithelial barrier was reversibly permeable when approached from beneath by the plasma exudate. This was a distinct increase in outward permeability, because even during the exudation of plasma the mucosa remained a barrier to luminal solutes. It is possible that the exudate itself, by a slight compressive action on the basolateral aspect of epithelial cells, creates intercellular pathways for its entry into the lumen. Contrary to current beliefs, we propose that plasma exudation should be considered a first line respiratory defence mechanism operating together with other systems of the mucosal surface.
    Type of Medium: Electronic Resource
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