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  • 1
    Electronic Resource
    Electronic Resource
    Nasal challenge studies with bradykinin: influence upon mediator generation (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 21 (1991), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous studies have shown that nasal allergen provocation leads to dose-dependent increases of inflammatory mediators, e.g. histamtne, kinins, LTC4 and PGD2 in nasal lavages. To investigte further the interaction of these mediators, a titration study with intranasal bradykinin (Bk) application (maximal dose 100 nmol/nostril) and consecutive lavage were performed in eight grass-pollen-allergic patients out of season, and five controls. The nasal lavages were analysed for albumin, N-α-tosyl-l-arginine methyl ester (TAME) esterase activity, histamine, 9α,11β-PGF2, and LTC4. The clinical reactions were mesured with a subjective symptom score. A dose-dependent elevation of albumin was found which was significantly higher in patients with allergic and non-allergic rhinitis compared with normal volunteers. TAME-eslerase activity also increased in relation to the dosage of Bk given without significant difference between the various groups. No influence on histamine, LTC4 and 9α,11β-PGF2, release (PGD2 metabolite) was seen. Short-lasting clinical symptoms like irritation, sneezing, and obstruction were noticed after the two highest Bk dosages (10 and 100 nmol). We conclude that intransally applied Bk induces a dose-dependent plasma leakage into the nasal cavity, which is significantly higher in patients with seasonal allergic rhinitis out of season compared to normals. Bk does not seem to affect the mast cell since hisiamine, LTC4 and 9αl lβ-PGF2 levels do not alter. The ability to induce relevant symptoms of rhinitis provides strong support for the hypothesis that kinins may be important mediators of inflammatory disorders of the upper airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1991.tb01682.x
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  • 2
    Electronic Resource
    Electronic Resource
    Topical vasoconstrictor (oxymetazoline) does not affect histamine-induced mucosal exudation of plasma in human nasal airways (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 22 (1992), S. 0 
    Details
    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
    URL: http://dx.doi.org/10.1111/j.1365-2222.1992.tb03103.x
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  • 3
    Electronic Resource
    Electronic Resource
    Plasma exudation as a first line respiratory mucosal defence (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 21 (1991), S. 0 
    Details
    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
    URL: http://dx.doi.org/10.1111/j.1365-2222.1991.tb00799.x
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  • 4
    Electronic Resource
    Electronic Resource
    Changes in non-specific nasal reactivity and eosinophil influx and activation after allergen challenge (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 20 (1990), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been suggested that the eosinophilic granulocyte plays a crucial role in the genesis of increased reactivity of the airways. In order to characterize changes in non-specific reactivity in the upper airways following a nasal allergen challenge further 16 subjects with strictly seasonal allergic rhinitis were studied. They were challenged with allergen outside the relevant pollen season and monitored at intervals for a period of 24 hr for nasal symptoms, changes in nasal reactivity, eosinophil influx and activation, and markers of inflammation. The same challenge sequence without an initial allergen challenge was used as a control. A symptom score technique was used to record nasal symptoms and methacholine challenges were used to monitor changes in non-specific reactivity. A nasal lavage was made prior to each methacholine challenge to monitor the influx of cells, specifically eosinophils, and to determine changes in the levels of eosinophil cationic protein (ECP) and TAME-esterase activity. Cells from the mucosal surface were also collected with a Rhinobrush® prior to the allergen challenge as well as at the 24-hr follow up. The allergen challenge induced a five-fold increase in non-specific nasal reactivity, as measured by the methacholine challenges, at the 2-hr follow up from 0·051 ml ± 0·012 (mean ± s.e.m.) to 0·255 ± 0·062 (P 〈 0·01) and a significant increase was also noted at all observation points, whereas no increases could be observed in the control setting. With a similar timing the allergen challenge also induced an increase in the proportion of eosinophils on the mucosal surface from an initial 0·8 ± 0·4% to 6·2 ± 2·1% of the cells as early as 2 hrs later (P 〈 0·05). A significant correlation was foundbetween the levels ofECP and eosinophils in the lavage fluid (r= 0·64, P 〈 0·001) and between the levels of ECP and TAME esterase (r= 0·43, P 〈 0·01). No correlations were, however, disclosed between the increases in non-specific nasal reactivity and the number of eosinophils (regardless of the cell-harvesting technique) or ECP levels at any of the observed time points. It is therefore suggested that the allergen-induced change in non-specific nasal reactivity is a complex phenomenon rather than just the recruitment and activation of eosinophilic granulocytes in the nasal cavity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1990.tb03147.x
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of azelastine on substance P content in bronchoalveolar and nasal lavage fluids of patients with allergic asthma (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 23 (1993), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The study was carried out to investigate the effect of azelastine on the Substance P (SP) concentration in bronchoalveolar (BAL) and nasal (NAL) lavage obtained from atopic grass pollen asthmatics and non-atopic healthy subjects. In BAL and NAL fluids there was a significant elevation in the baseline concentration of SP between asthmatics and volunteers. Allergen provocation induced a rise of SP in BAL and NAL in asthmatics, but not in volunteers. Azelastine pre-treatment resulted in a significant reduction of SP in baseline concentration of SP in BAL and NAL from asthmatics. An elevation of SP in BAL or NAL fluids after allergen provocation was not seen in asthmatics pretreated with azelastine. Azelastine did not influence the SP concentration in BAL and NAL of volunteers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1993.tb02486.x
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  • 6
    Electronic Resource
    Electronic Resource
    Tryptase in nasal lavage fluid after local allergen challenge: Relationship to histamine levels and TAME-esterase activity (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 46 (1991), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10-fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME-esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME-esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME-esterase levels and the tryptase levels (r = 0.71; P 〈 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non-allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1991.tb04362.x
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  • 7
    Electronic Resource
    Electronic Resource
    Suppresive effect of loratadine on allergen-induced histamine release in the nose (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 46 (1991), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been speculated whether the recently developed non-sedating antihistamines may possess other properties than merely being antagonists at the H1-receptors. To investigate this suggestion 12 patients with strictly seasonal allergic rhinitis participated in a double-blind placebo controlled randomized cross-over study outside the pollen season. At steady state levels of 10 mg loratadine, a new non-sedating antihistamine, the patients were challenged with methacholine. This was followed by a nasal challenge with increasing doses of allergen. 24 h later the patients were rechallenged nasally with the same methacholine dose as the day before. The volume of the methacholine-induced nasal secretion was measured and the response to allergen was determined by scoring technique. In returned nasal lavage fluid the levels of histamine and TAME-esterase activity were measured. It was found that loratadine significantly reduced the immediate allergic nasal symptoms compared with placebo (P 〈 0.01). Loratadine also reduced the allergen-induced release of histamine into the nasal cavity after the strongest allergen dose, from 9.6±1.5 (mean ± SEM) to 6.4±1.4 ng/ml (P 〈 0.05). A similar decrease in the TAME-esterase activity after treatment with loratadine was observed. The TAME-esterase activity decreased from 11.6 *103±2.47 *103 to 5.60 *103±1.45 */103 CMP (P 〈 0.05). There were no significant changes between the active and placebo treatments regarding the methacholine-induced secretory response. This was true for the initial methacholine challenge as well as the secretory response 24 h later. This study shows that loratadine is an effective drug in the suppression of immediate allergic nasal symptoms. One of the beneficial effects of this drug could be a reduction in allergen-induced histamine release. A finding which further implicates that antihistamines may possess other effects than just a blocking of the H1-receptor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1991.tb00618.x
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  • 8
    Electronic Resource
    Electronic Resource
    Tryptase in nasal lavage fluid after local allergen challenge: Relationship to histamine levels and TAME-esterase activity (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 46 (1991), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10-fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME-esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME-esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME-esterase levels and the tryptase levels (r = 0.71; P 〈 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non-allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1991.tb04225.x
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  • 9
    Electronic Resource
    Electronic Resource
    Kinin generation following methacholine nasal airway challenge of non-allergic subjects (1992)
    Springer
    European archives of oto-rhino-laryngology and head & neck 249 (1992), S. 318-321 
    Details
    ISSN: 1434-4726
    Keywords: Chronic non-allergic rhinitis ; Kinins ; Methacholine challenge ; Muscarinic receptor stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following nasal challenges with the muscarinic neurotransmitter methacholine in 14 patients with chronic non-allergic rhinitis, kinin generation was induced. This occurrence was inhibited by pretreatment with anticholinergic agents (ipratropium bromide) and by an overdose of neurotransmitter, indicating that a muscarinic receptor is stimulating the liberation of kinin. These observations suggest that patients with chronic non-allergic rhinitis exhibit cholinergic neurotransmitter-induced kinin generation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00179380
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