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

Allergic rhinitis (AR) is the most common chronic condition in children and is estimated to affect up to 40% of all children. It is usually diagnosed by the age of 6 years. The major impact in children is due to co-morbidity of sinusitis, otitis media with effusion, and bronchial asthma. AR also has profound effects on school absenteeism, performance and quality of life. Pharmacotherapy for AR should be based on the severity and duration of signs and symptoms. For mild, intermittent symptoms lasting a few hours to a few days, an oral second-generation antihistamine should be used on an as-needed basis. This is preferable to a less expensive first-generation antihistamine because of the effect of the latter on sedation and cognition. Four second-generation antihistamines are currently available for children under 12 years of age: cetirizine, loratadine, fexofenadine and azelastine nasal spray; each has been found to be well tolerated and effective. There are no clearcut advantages to distinguish these antihistamines, although for children under 5 years of age, only cetirizine and loratadine are approved. Other agents include pseudoephedrine, an oral vasoconstrictor, for nasal congestion, and the anticholinergic nasal spray ipratropium bromide for rhinorrhoea. Sodium cromoglycate, a mast cell stabiliser nasal spray, may also be useful in this population. For patients with more persistent, severe symptoms, intranasal corticosteroids are indicated, although one might consider azelastine nasal spray, which has anti- inflammatory activity in addition to its antihistamine effect. With the exception of fluticasone propionate for children aged 4 years and older, and mometasone furoate for those aged 3 years and older, the other intranasal corticosteroids including beclomethasone dipropionate, triamcinolone, flunisolide and budesonide are approved for children aged 6 years and older. All are effective, so a major consideration would be cost and safety. For short term therapy of 1 to 2 months, the first-generation intranasal corticosteroids (beclomethasone dipropionate, triamcinolone, budesonide and flunisolide) could be used, and mometasone furoate and fluticasone propionate could be considered for longer-term treatment. Although somewhat more costly, these second-generation drugs have lower bioavailability and thus would have a better safety profile. In patients not responding to the above programme or who require continuous medication, identification of specific triggers by an allergist can allow for specific avoidance measures and/or immunotherapy to decrease the allergic component and increase the effectiveness of the pharmacological regimen.
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PMID:Clinical prescribing of allergic rhinitis medication in the preschool and young school-age child: what are the options? 1152 Feb 56

IgE-mediated mast cell and basophil activation initiates immediate and late-phase allergic responses, and plays a pivotal role in the pathogenesis of allergic diseases such as bronchial asthma and allergic rhinitis. Thus, the blocking of the binding of IgE to the high affinity receptors for IgE (Fc epsilon RI) on mast cells and basophils may prevent dual responses, and improve allergic symptoms. A recombinant humanized monoclonal antibody (rhuMAb-E25) forms complexes with free IgE, blocks its binding to mast cells and basophils, and inhibits allergen-induced mediator release from both cells and attenuates immediate and late-phase reactions to inhaled allergens. In clinical trials, the therapy with rhuMAb-E25 was effective in patients with atopic asthma and allergic rhinitis and well tolerated. This antibody seems to be promising as a treatment for atopic asthma and allergic rhinitis.
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PMID:[Treatment of allergic diseases with monoclonal anti-IgE antibody]. 1167 48

The incidence of allergic diseases is increasing to epidemic proportions both in the developed and developing world with increasing medical costs and lost productivity. The discovery of immunoglobulin (Ig) E heralded a new era in pathophysiological understanding of allergic disorders. Twenty-five years later, a humanised, non-anaphylactogenic antibody was developed against IgE that could provide a therapeutic alternative to the existing medications. RhuMAb-E25 (omalizumab, Xolair, Genetech, Inc.) is a novel anti-IgE antibody that is directed against the receptor-binding domain of IgE. This binding is specific towards free IgE thereby preventing it from attaching to the mast cell and its subsequent activation. Initial studies demonstrated attenuation of the early and late asthmatic responses when anti-IgE was administered to asthmatic subjects. Later this novel molecule was found to improve symptom scores, rescue medication use, quality of life scores and peak expiratory flows in patients with allergic asthma. Most importantly, omalizumab treatment reduced the corticosteroid use in asthmatic individuals. In patients with seasonal allergic rhinitis, there was a significant reduction in the nasal and ocular symptoms as well as the use of rescue medications. Omalizumab also demonstrated a high level of safety in adults, adolescents and children with a side effect profile no different from the placebo. Its development is an exciting milestone in the treatment of allergic diseases.
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PMID:Omalizumab, a novel anti-IgE therapy in allergic disorders. 1172 35

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.
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PMID:Possible role of plasminogen activator in the occurrence of profuse watery rhinorrhea after topical application of epinephrine to the nasal mucosa. 1182 93

The pathogenesis of allergic rhinitis can be better appreciated by understanding the numerous protective mechanisms available for mucosal defense. The system of TH2 lymphocytes, IgE production, mast cell degranulation, eosinophil infiltration, and resident cell responses are central to our understanding and treatment of allergic rhinitis. Histamine remains preeminent in causing the cardinal symptoms of the immediate allergic reaction: itching, watery discharge, and nasal swelling. Recruitment and activation mechanisms responsible for the late-phase allergic response are also reviewed.
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PMID:Mechanisms of allergic rhinitis. 1189 38

Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic diseases. Cross-linking of IgE molecules on mast cell and basophil surface membrane by allergens, triggers the release of multiple mediators, leading to the development of IgE-mediated immediate and late hypersensitivity reactions. In view of the pivotal role of IgE, it became an attractive target for intervention in the treatment of allergic diseases. Murine monoclonal non-anaphylactogenic antibodies directed to the receptor-binding domain of IgE, were found to reduce IgE levels and production. Anti-IgE antibodies have been recently evaluated in several clinical trials involving hundreds of asthmatic patients both adults and children, including patients with allergic rhinitis. Clinical efficacy and good tolerability were demonstrated. This novel therapeutic approach also appears to be promising for potential treatment of patients suffering concomitantly from several allergic disorders.
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PMID:[Anti-IgE--a new treatment for allergic diseases]. 1194 20

Haptoglobin (Hp) is an acute phase reactant produced by hepatocytes. There is evidence for an immunomodulatory potential of Hp, though there is no clear evidence yet about the mechanisms of this action. We have previously shown that Hp interacts with the beta2-integrin CD11b/CD18. In addition, other investigators reported the binding of Hp to B lymphocytes through the CD22 receptor, and to neutrophils through two different receptors. In the present study, we investigated the interaction of haptoglobin with the human mast cell line HMC-1. We report that fluorescein isothiocyanate (FITC)-labelled haptoglobin binds to this cell line and that binding is increased by calcium in a dose- and time-dependent manner. Hp binding sites on HMC-1 were upregulated upon stimulation with phorbol myristate acetate (PMA)/A23187 and after treatment with anti-CD43 and anti-CD44 monoclonal antibodies (MoAbs). HMC-1 cells do not express either CD11b/CD18 or CD22 receptors, indicating that the haptoglobin-binding receptor on this cell line is different from the known receptors. Assessment of cell function showed that Hp inhibits the spontaneous growth of HMC-1 up till 40% at higher Hp concentrations, but it did not exhibit any effect on the expression of CD54 on the release of either tryptase or IL-1ra. In conclusion, haptoglobin binds specifically to human mast cells via a receptor different from CD11b/CD18 and CD22, and may play a role in the modulation of mast cell functions. Exploration of Hp effects in mast cell-dependent diseases such as allergic rhinitis and urticaria seems warranted.
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PMID:Haptoglobin interacts with the human mast cell line HMC-1 and inhibits its spontaneous proliferation. 1196 16

Primary principles relevant to the clinical management of allergic rhinitis include (1) avoidance of allergens and triggering factors, (2) use of appropriate pharmacotherapy, (3) evaluation regarding need for and appropriate use of immunotherapy, and (4) patient education and follow-up. Currently available pharmacotherapeutic options include oral and topical (intranasal) decongestants and corticosteroids, mast cell stabilizers, intranasal anticholinergics, and antihistamines. Future therapeutic options include leukotriene modifiers and anti-IgE antibodies.
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PMID:Improved strategies and new treatment options for allergic rhinitis. 1209 Jun 44

Data from in vitro, in vivo, and ex vivo studies suggest that second-generation antihistamines have a number of antiallergic, anti-inflammatory properties that appear to be independent of their H1-blockade activity. First-generation antihistamines also have antiallergic, anti-inflammatory properties, as suggested by the studies with azatadine, chlorpheniramine, mepyramine, and promethazine; most other first-generation antihistamines have not been studied for these properties. In vitro studies have shown that H1-antihistamines reduce the release of proinflammatory mediators from mast cells and basophils, the chemotaxis and activation of inflammatory cells (especially eosinophils), and the expression of adhesion molecules induced by immunological and nonimmunological stimuli in epithelial cell lines. Nasal allergen challenge models have similarly demonstrated that H1-antihistamines inhibit mediator release from mast cells and basophils, and that they decrease inflammatory cell infiltration and the expression of adhesion molecules on epithelial cells. The results of published studies of the effects of H1-antihistamines on nasal allergic inflammation in humans have been summarized in this chapter. Recent investigations indicate that H1-antihistamines may modulate airway inflammation by downregulating the activity of airway epithelial cells, which have an important role in allergic airway inflammation. The modulation of adhesion molecules and of inflammatory cell infiltration by H1-antihistamines may be beneficial during long-term treatment in patients with allergic rhinitis. The rationale for this hypothesis is the persistence of inflammation on the nasal epithelial cells even when patients are symptom-free (16). All of the events affected by H1-antihistamines are important in the allergic inflammation cascade. The underlying mechanisms for such effects remain unclear, but are unrelated to H1-antagonist activity. Several studies have demonstrated that H1-antihistamines can form an ionic association with cell membranes and inhibit calcium ion influx into the mast cell or basophil plasma membrane, or inhibit Ca2+ release within the cells, and may therefore influence the signal transduction pathways. However, these effects appear to occur at concentrations higher than those achieved in therapeutic practice (126-128). It has recently been hypothesized that the anti-inflammatory activity of H1-antihistamines may be a consequence of their ability to influence the activation of genes responsible for the expression and synthesis of proinflammatory mediators (129). The contribution of the antiallergic effects of H1-receptor antagonists to their clinical efficacy is not fully understood. There have been no data suggesting that H1-antihistamines with well-documented antiallergic properties are superior to the others for which such properties have not been as extensively investigated. Additional studies are needed to elucidate the mechanisms(s) by which H1-antihistamines exert anti-inflammatory effects. This knowledge might lead to the development of novel therapies with more potent and specific anti-inflammatory effects.
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PMID:Antiallergic anti-inflammatory effects of H1-antihistamines in humans. 1211 15

Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -- for reasons that remain to be established -- that asthma occurs.
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PMID:New insights into the relationship between airway inflammation and asthma. 1214 12


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