Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An in vivo model of human allergic disease has been developed in which nasal challenge with antigen leads to physiologic changes, together with a release of increased amounts of inflammatory mediators into nasal secretions obtained by washing the nose with saline. In 105 experiments involving 35 subjects, only allergic subjects consistently demonstrated an increase in the concentrations of the mast cell mediator, histamine, and the putative mast cell mediators, TAME-esterase and PGD2. The release of each mediator was significantly (p less than 0.001) related to the physiologic change (sneezing). The release of each mediator also correlated significantly with the release of the other 2 mediators (p less than 0.001). This system, for the first time, clearly relates an in vivo symptom and mediator release and thus should provide an excellent tool for the further study of the allergic response and nasal pathophysiology.
 ...
PMID:Mediator release after nasal airway challenge with allergen. 635 22

Antihistamines are believed to reduce the sneezing and rhinorrhea associated with allergic rhinitis, primarily by competitive antagonism of histamine for H1 cellular receptors, but additional mechanisms of action may contribute to their clinical efficacy. To improve our understanding of H1 antihistamine action, we studied the effects of pretreatment with terfenadine, cetirizine, ketotifen, azatadine, diphenhydramine, and azelastine on increases in vascular permeability, mast cell activation, and sneezing induced by nasal challenge with antigen. All studied antihistamines reduced sneezing, indicating that they all effectively antagonize histamine after its release. In addition, terfenadine and topically administered azatadine blocked the release of histamine. Studies with cetirizine and azelastine revealed that these antihistamines significantly reduced sulfidopeptide leukotriene levels. Terfenadine and azelastine also reduced kinin production. These results confirm that antihistamines are effective in reducing sneezing and, in some cases, vascular permeability. The findings of these studies also illustrate that the various antihistamines have multiple and different mechanisms of action that may have implications for their clinical uses.
 ...
PMID:The effect of antihistamines on the immediate allergic response: a comparative review. 810 58

Nasal biopsies to naturally occurring allergic rhinitis demonstrate ultrastructural evidence of mast cell degranulation. Consistent with this, H1 antihistamines are clinically efficacious in this disorder. The nasal symptoms of itch, sneeze and discharge are, however, more susceptible to this mode of therapy than is nasal blockage. As nasal blockage is vascular, the combination of an H1 antihistamine and a decongestant has a logical rationale. To investigate the efficacy of such a combination, the influence of pretreatment with terfenadine, 60 mg, pseudo-ephedrine, 120 mg, Seldane-d (a registered trademark of Marion Merrell Dow)--a combination of pseudo-ephedrine, 120 mg, and terfenadine, 60 mg,--and matched placebo was objectively investigated on the nasal response to allergen in grass-pollen-sensitive seasonal rhinitic subjects (7 males, 7 females, age 19-56 years) in a double-blind, placebo-controlled, 4-period cross-over study. Seldane-D was significantly better than placebo in all efficacy measurements: nasal itch (p < 0.02), sneezing (p < 0.01), discharge (p < 0.01) and blockage (p < 0.003). The terfenadine component of Seldane-D contributed predominantly to the reduction in itch, sneeze and discharge (p < 0.01) while the pseudo-ephedrine component primarily contributed to the nasal airway effects (p < 0.04). These results indicate that the combination of terfenadine and pseudo-ephedrine as a single oral medication is complementary.
 ...
PMID:The influence of terfenadine and pseudo-ephedrine alone and in combination on allergen-induced rhinitis. 832 95

The pathogenesis of allergic rhinitis is complex, involving not only histamine and mast cell-derived tryptase, but also eosinophil- and neutrophil-derived mediators, cytokines, and intercellular cell adhesion molecules (ICAM-1). It is surprising that antihistamines, which block only one component of the process, have proved so effective in the management of allergic rhinitis. Research has therefore focused on whether antihistamines have additional pharmacological activities. In vitro studies have shown that high concentrations of second generation antihistamines can block inflammatory mediator release from basophils and mast cells, and reduce ICAM-1 expression in epithelial cell lines. In vivo studies have also shown an effect on the allergen-induced inflammatory reaction; both oral and intranasal antihistamines cause a reduction in nasal symptoms and inflammatory cell influx. Oral terfenadine and cetirizine and intranasal levocabastine and azelastine have also demonstrated a lowering of ICAM-1 expression on epithelial cells. With regard to clinical efficacy, topical levocabastine (0.5 mg/mL eye drop solution and 0.5 mg/mL nasal spray) was shown to be more effective than oral terfenadine (60 mg twice daily) in relieving ocular itch (P = 0.02) and reducing nasal symptoms in allergic rhinoconjunctivitis. In a further study, levocabastine eye drops were as effective and well tolerated as sodium cromoglycate in seasonal allergic rhinitis. Intranasal azelastine (0.28 mg twice daily) showed a trend for superior relief of rhinorrhoea and nasal obstruction compared with oral terfenadine (60 mg twice daily). In addition, intranasal azelastine (0.28 mg twice daily) resulted in significant reductions in sneezing, nasal obstruction, rhinorrhoea and itching in perennial rhinitis, compared with the lower efficacy of beclomethasone dipropionate (0.1 mg twice daily). As well as benefits in efficacy, topical administration is associated with improved safety. Some antihistamines, particularly those metabolized in the liver, are associated with occasional reports of severe side-effects. It is therefore logical to administer antihistamines directly to the target organ.
 ...
PMID:Antihistamines: topical vs oral administration. 873 53

Allergic rhinitis involves an early phase, largely mediated through mast cells, and a late phase which involves cellular infiltration and mediator release. In the early phase, mast cells release mediators as a result of antigen cross-linking adjacent immunoglobulin E molecules bound to mast cell surfaces. This results in an accumulation of histamine which gives rise to the characteristic symptoms of rhinitis--sneezing, itching, rhinorrhoea and congestion. The late phase of the allergic response (hours after challenge) involves infiltration of the nasal epithelium by eosinophils, basophils, monocytes and T-lymphocytes, which release leukotrienes, kinins, histamine and a host of other mediators. The most important part of the late-phase response is probably mediated via the production of cytokines (IL-4, IL-5, IL-6, IL-8, GM-CSF and RANTES) by mast cells, TH2 lymphocytes or epithelial cells. The infiltration of tissues by cells normally present only in the blood is brought about by the production of adhesion molecules, such as VCAM-1 and E-selectin, which cause circulating eosinophils, basophils and T-lymphocytes to adhere to endothelial cells before moving through the endothelium into the tissue (diapedesis). Neuronal reflexes also play a role in the allergic response, both by mediating local responses to mediators and possibly playing a part in the activation of T-lymphocytes. The allergic response has also been shown to be less intense in a hot, humid environment, and more marked in a cold, dry environment, possibly due to changes in osmolality of the nasal surface fluid. Similar factors may play a role in the aetiology of non-allergic rhinitis.
 ...
PMID:Pathophysiology of perennial allergic rhinitis. 921 57

The allergic inflammatory response in allergic rhinitis has been studied extensively owing to the high frequency of the condition, the significant morbidity it causes and the accessibility of the nasal tissue. The allergic inflammatory response is characterized by IgE synthesis, IgE-dependent mast cell activation and infiltration of the nasal mucosa by T lymphocytes and eosinophils. The immediate-phase response is mediated by a range of inflammatory mediators (such as histamine, leukotrienes and prostaglandins), resulting in vasodilatation, oedema, mucus secretion, itching and sneezing. Individuals who experience a late-phase response have further nasal symptoms 4-24 h after the initial challenge with allergen. Results of nasal biopsy studies indicate that the late-phase allergic response involves T-lymphocyte activation, production of TH2-type cytokines and tissue eosinophilia. Corticosteroids potently inhibit T-lymphocyte responses, and clinical studies in subjects with allergic rhinitis have demonstrated that they are extremely effective in blocking both early- and late-phase allergic reactions. Topical aqueous triamcinolone acetonide nasal spray represents a novel formulation of a topical corticosteroid for the treatment of allergic rhinitis. Data from controlled clinical studies indicate that it is effective in treating seasonal and perennial disease, is well tolerated, does not suppress adrenocortical function, is odourless, and can be administered as a once-daily dose.
 ...
PMID:The inflammatory nature of allergic disease. 998 30

Two assays have been done to evaluate the effect of immunotherapy in nasal allergy. First, a trial of nasal immunotherapy and second, the study of mediator release after vaccines. Local immunotherapy, applied directly, triggers different response mechanisms. Specific nasal immunotherapy started before seasonal or perennial symptoms peak, has been done by increasing the doses of allergen three times a week during a 3-month period and a manutention period of a weekly nasal puff of the same allergen. Symptom scores and drug consumption have been registered. The results have been compared with the scores obtained in the same patients over the same period of the same year before immunotherapy. In perennial rhinitis blockage, rhinorrea, sneezing and itching scores all decreased. In seasonal rhinitis, a similar score decrease was obtained for blockage, rhinorrea, sneezing and itching. Pharmacological scores also decreased. These data point to a short-term effect of nasal immunotherapy. Tryptase release has been evaluated in nasal washings after nasal challenge with a Parietaria (Pellitory wall) extract before and after specific systemic immunotherapy, in order to evaluate changes in mast cells reactivity. Eight patients were studied, all allergic to Parietaria. Nasal provocation tests have been done before the season with increasing doses of 10, 100 and 1000 PNU and tryptase assayed in nasal washings at 10, 20 and 30 min after provocation. Immunotherapy decreased tryptase release after nasal challenge. The data point to the effect of systemic specific immunotherapy on mast cell reactivity.
 ...
PMID:Local and systemic immunotherapy in nasal allergy. 1057 7

The mode of action of intranasal corticosteroids (INCS) is complex. It is not known whether INCS penetrate the nasal mucosa or act on target cells; however, their low systemic activity supports the concept of local action on nasal mucosa. This local effect can nonetheless influence a variety of inflammatory cells and their mediators such as epithelial cells, lymphocytes, basophils, mast cells, and Langerhans cells. Corticosteroid-induced inhibition of immunoglobulin E-dependent release of histamine is a possible but unproven mode of action. Epithelial cells are an important target for corticosteroids, and INCS concentration is high at the epithelial surface. INCS may combine with the corticosteroid receptors in epithelial cells, which are then expelled into the airway lumen together with the dead epithelial cells or migrating inflammatory cells. A reduced influx of mediator cells may explain some of the effects of INCS on rhinitis symptoms, but it cannot explain all of the effects because INCS also reduce the early-phase sneezing and rhinorrhea after an allergen challenge outside the pollen season. In this situation, the number of surface mast cells/basophils is very low, as it is in the absence of allergic rhinitis. The mechanism by which INCS treatment of allergic rhinitis reduces itching, sneezing, and rhinorrhea, the characteristic symptoms of an early-phase response involving mast cell release of histamine, remains to be determined. Studies should be conducted to characterize the broad range of mechanisms by which INCS produce their therapeutic effects in allergic rhinitis.
 ...
PMID:Mode of action of intranasal corticosteroids. 1144 2

Prostaglandin (PG) D2, the major cyclooxygenase metabolite generated from immunologically stimulated mast cells, is thought to contribute to the pathogenesis of allergic diseases due to its various inflammatory effects. However, since no DP receptor antagonist has been developed as an antiallergic drug, the role of PGD2 in the pathogenesis of allergic diseases remains uncertain. Here, we report the in vivo efficacy of our newly established DP receptor antagonist, S-5751 [((Z)-7-[(1R,2R,3S,5S)-2-(5-hydroxy benzo[b]thiophen-3-ylcarbonylamino)-10-norpinan-3-yl]hept-5- enoic acid)], using various allergic inflammation guinea pig models. In allergic rhinitis models, oral administration of S-5751 dramatically inhibited not only early nasal responses, as assessed by sneezing, mucosal plasma exudation, and nasal blockage, but also late responses such as mucosal plasma exudation and eosinophil infiltration. Even when S-5751 was administered after recovery from the early responses, these late phase responses were almost completely suppressed. In addition, S-5751 alleviated allergen-induced plasma exudation in the conjunctiva in an allergic conjunctivitis model and antigen-induced eosinophil infiltration into the lung in an asthma model. These findings provide evidence for the crucial role of PGD2 as a mediator of allergic inflammation in guinea pigs and suggest that DP receptor antagonists may be useful in the treatment of allergic diseases triggered by mast cell activation.
 ...
PMID:Prevention of allergic inflammation by a novel prostaglandin receptor antagonist, S-5751. 1145 1

Epinephrine and lidocaine have been used for the diagnosis and treatment of nasal diseases. However, watery rhinorrhea and frequent sneezing occur in many patients after topical application of these drugs to the nasal mucosa. This study was aimed at characterizing these side effects, and developing a means to prevent such side effects. A questionnaire was given to each patient who complained of side effects after treatment with epinephrine and lidocaine, and the answers were analyzed with respect to the occurrence and features of the symptoms after the treatment. Eosinophil and mast cell numbers were determined in nasal smears from the patients with side effects. These side effects were different from rhinitis medicamentosa and allergic rhinitis, and were due to epinephrine, not to lidocaine or to the preservatives in the epinephrine. Tranexamic acd, an inhibitor of plasmin, was effective in blocking the side effects.
 ...
PMID:Possible role of plasminogen activator in the occurrence of profuse watery rhinorrhea after topical application of epinephrine to the nasal mucosa. 1182 93


<< Previous 1 2 3 4 5 6 Next >>