Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exercise is a physical cause of allergic reactions, including exercise-induced anaphylaxis (EIAna), exercise-induced urticaria (EIU), exercise-induced asthma (EIA), and exercise-induced rhinitis (EIR). Since its first description in 1979, EIAna has been reported with variable clinical manifestations, with exercise alone, and in combination with food ingestion. Elevated serum histamine levels and cutaneous mast cell degranulation have been noted. Exercise-induced urticaria appears as small, punctate lesions that differ from the classic coalescent type seen with EIAna. Variant forms of EIAna with cholinergic urticarial lesions manifesting systemic collapse and/or respiratory distress have been studied. Exercise-induced urticaria and cold-induced urticaria may cause elevated plasma histamine levels coincident with the onset of pruritus and hives. Theories accounting for EIA include respiratory heat loss, water loss, and mast cell activation. Although some studies have shown increased plasma histamine with EIA, others have not. Recently, bronchoalveolar lavage in atopic subjects with EIA has been evaluated preexercise and postexercise, with no significant differences in histamine or tryptase, suggesting a pathogenesis of EIA independent of the mast cell. Exercise-induced rhinitis, with varying degrees of rhinorrhea, congestion, and sneezing, has been increasingly recognized in athletes who run, cycle, and ski. Cold-air-induced rhinorrhea in laboratory challenges displays a mediator release pattern similar to that produced by allergen-induced nasal challenges. Therapeutically, H1 antihistamines are recommended for EIAna both as pretreatment and acute therapy. H1 antihistamines may be helpful in EIU, but are recommended for EIAna both as pretreatment and acute therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exercise-induced allergies: the role of histamine release. 137 Oct 41

To examine mast cell involvement in allergic rhinitis, levels of tryptase, a specific marker for mast cell activation, and histamine, a marker of mast cell and basophil activation, were measured in nasal-lavage fluid after nasal-allergen challenge. Twelve atopic subjects with allergic rhinitis and five nonatopic subjects were challenged with timothy grass or ragweed pollen at increasing doses of allergen. Tryptase and histamine levels were determined by an ELISA and radioenzyme assay, respectively; clinical responses were measured by assessment of sneezing, rhinorrhea, nasal congestion, and ocular tearing or itching. A positive clinical response was observed in seven of the atopic subjects and in none of the nonatopic subjects. Tryptase levels increased at least sevenfold higher than baseline levels in 100% of the atopic clinical responders and reached a maximum at the same dose of allergen where clinical symptoms were maximal. In contrast, histamine levels were only threefold or greater elevated in five of seven atopic clinical responders at this dose of allergen. (Histamine levels were lower in one subject and were only 50% higher in another subject than the corresponding baseline value.) Histamine levels and symptom scores were maximal at the same dose of allergen in only four of seven clinical responders. Overlap of peak mediator levels in subjects without a clinical response with those of the clinical responders occurred only in the case of histamine. Tryptase levels in nasal-lavage fluid appear promising as a useful indicator of allergic reactions and indicate that mast cell activation is the major factor in the immediate nasal-allergic response.
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PMID:Tryptase levels in nasal-lavage fluid as an indicator of the immediate allergic response. 304 43

Seventeen out of thirty-three workers who have been exposed to airborne papain at their place of work regularly developed asthmatic symptoms such as shortness of breath, wheezing, coughing, sneezing, rhinorrhea and conjunctival irritation upon contact with this proteolytic enzyme. Investigations by RAST, skin test and bronchial provocation test proved IgE-mediated hypersensitivity to papain in fourteen symptomatic workers. Ten of these were in a screening investigation involving twenty-nine of the thirty-three workers; i.e. the incidence of IgE-mediated sensitization was 34.5% of this group. Bronchial provocation of as little as 0.001--0.5 mg of papain was shown to elicit immediate or dual asthmatic reactions in all eight tested workers with RAST values greater than 3 u/ml. On the other hand, inhalation of 0.5 mg of papain did not cause any remarkable change in non-exposed asthmatics. Occupation-related blood-stained nasal secretions and/or cutaneous flare reactions in all four heavily-exposed papain workers, of whom three had negative skin test and RAST results, suggest a direct effect of the proteolytically active enzyme on human tissue. There was a significant elevation (P less than 0.001) of serum trypsin inhibitory capacity in papain workers which seems to depend on the degree of exposure. No significant differences between symptomatic and asymptomatic workers in alpha 1-antitrypsin (Pi) phenotype subtypes were found.
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PMID:Clinical symptoms and results of skin test, RAST and bronchial provocation test in thirty-three papain workers: evidence for strong immunogenic potency and clinically relevant 'proteolytic effects of airborne papain'. 703 63

The nasal antigen challenge model has proved useful in assessing the roles of inflammatory mediators in the clinical allergic response. Studies using this model have revealed that the acute allergic response is associated with increased concentrations of histamine, prostaglandin D2 (PGD2), leukotrienes, tryptase, and kinins, and with increased TAME-esterase activity. The effects of antihistamines on the clinical response and inhibition of mediator release have also been examined with this model. Premedication with terfenadine caused a marked reduction in sneezing as well as decreased histamine release, kinin levels, and TAME-esterase activity. Levels of PGD2 also decreased, although not significantly. Release of leukotriene C4 (LTC4) was not affected by this agent. Terfenadine also reduced vascular permeability as reflected in decreased albumin levels. In this model, cetirizine reduced sneezing, TAME-esterase activity, and albumin levels, whereas histamine release and PGD2 levels remained unaffected. Pretreatment with cetirizine resulted in significantly reduced levels of LTC4. Loratadine markedly, but not significantly, inhibited the sneezing response and reduced release of histamine, PGD2, and LTC4. Albumin and kinin levels were significantly diminished. The clinical significance of the inhibitory effects of antihistamines on mediator release has yet to be determined.
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PMID:Effects of antihistamines on inflammatory mediators. 769 May 26

Two experiments were performed during the pollen season to study the activity of different antiallergic drugs in the treatment of seasonal allergic rhinitis. Nasal allergen challenge (NAC) was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction during the season. The first study assessed the effect of H1 (Cetirizine 10 mg a day) and of a combination of H1 (Cetirizine 10 mg) plus H2 (Cimetidine 800 mg a day) antagonists on nasal symptoms, mediator release and eosinophil count in a group of 16 patients with seasonal allergic rhinitis. During the same season a second study compared in a randomized way (2 parallel groups) the effect of Budesonide (Rhinocort Aqua) and Azelastine (Allergodil nasal spray) in a group of 14 patients. Results showed that both antihistamines, applied topically of dosed orally, reduced sneezing even when significant increases of histamine concentration in nasal secretions were evidenced immediately after NAC. When a combination of Cetirizine and Cimetidine was administered, a significant (p < 0.01) reduction of nasal airway resistance and increase of nasal airflow after NAC were demonstrated as well. In addition, topical application of Budesonide showed a strong (p < 0.01) effect on the infiltration and activation of eosinophils during the season, and on tryptase release after NAC. These effects lasted at least for one week after therapy.
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PMID:The activity of recent anti-allergic drugs in the treatment of seasonal allergic rhinitis. 866 68

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.
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PMID:Antihistamines: topical vs oral administration. 873 53

During the pollen season, quantitative determination of the chemical mediators and eosinophil count was performed in 16 patients with hay fever after nasal allergen challenge (NAC). The aim of this study was objectively to assess the effect of H1 and of a combination of H1 and H2 antagonists on nasal symptoms, mediator release, and eosinophil count during an allergic reaction. NAC was performed at baseline (V1), 2 weeks after treatment with cetirizine 10 mg/day (V2), and after a combined therapy with cetirizine 10 mg and cimetidine 800 mg a day during the following week (V3). Results showed a significant (p < 0.05 or p < 0.01) relief of nasal symptoms such as: itching, sneezing, rhinorrhea and congestion, and of objective parameter such as: reduction of the number of sneezes after NAC at V2 and V3. Neither H1 antagonist nor a combination of H1 and H2 antagonists showed any effect on eosinophilia and ECP concentration caused by natural allergen exposure, nor on histamine and tryptase release immediately after NAC. When a combination of H1 and H2 antagonists was administered significant reduction of the nasal airway resistance and increase of the nasal air flow were demonstrated.
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PMID:Effect of H1 and H2 antagonists on nasal symptoms and mediator release in atopic patients after nasal allergen challenge during the pollen season. 882 Mar 58

Quantitative determinations of the inflammatory mediators in nasal secretions were performed and correlated with the objective nasal symptoms within 1 h after nasal allergen challenge (NAC). Twenty-six patients with seasonal allergic rhinitis were enrolled outside the pollen season. All measurements were performed before (as a baseline control) and at 1, 5, 10, 30, and 60 min after NAC. This study aimed to clarify the pathogenic mechanism of the early-phase reaction (EPR) by monitoring the evolution of early-phase mediators in nasal secretions and the presence of nasal symptoms during this period. The results showed that, after NAC, the maximal mediator concentration was already reached after 1 min for histamine (124 ng/g), 5 min for tryptase (56 microU/g), and 5-10 min for leukotriene C4 (40 ng/g). Itching and sneezing started as early as 20-30 s, and they were predominant symptoms within 5 min. Rhinorrhea and nasal obstruction started a few minutes after NAC and lasted until more than 1 h after NAC. There was no significant correlation between any single mediator and nasal symptoms during the sampling period. In conclusion, this study demonstrated that during the EPR the presence of nasal symptoms involves a complex mechanism, reflecting the interaction between the mediators released by inflammatory cells, and the receptors on different target organs. When evaluating symptoms during the EPR, one must consider not only the severity of these symptoms but also the time period within which these symptoms occur. For the symptoms of nasal obstruction and rhinorrhea, the early-phase reaction often lasted more than 1 h.
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PMID:An approach to the understanding of the nasal early-phase reaction induced by nasal allergen challenge. 910 20

The currently available respiratory topical corticosteroids are all effective at reducing the nasal symptoms of itch, sneezing, rhinorrhoea and obstruction associated with allergic rhinitis. The mechanism of action of corticosteroids is related to their anti-inflammatory activities. They have been documented to prevent fluid exudation and reduce the number of circulating inflammatory cells, including lymphocytes, mast cells, basophils, eosinophils, macrophages, and neutrophils. This occurs through multiple mechanisms, e.g. eosinophil infiltration is suppressed by preventing cytokine production, reducing local mechanisms of tissue infiltration, and decreasing eosinophil survival. Furthermore, corticosteroids also reduce preformed and newly-generated mediators (e.g. histamine, tryptase, prostanoids, leukotrienes), and inhibit production of cytokines and chemokines by inflammatory cells (e.g. IL-1 through IL-6, IL-8, RANTES, TNF-alpha, IFN-gamma and GM-CSF). The currently available corticosteroids differ pharmacologically. Fluticasone propionate appears to have the greatest affinity for the glucocorticoid receptor, and binds more quickly and dissociates more slowly from the receptor compared with other corticosteroids, suggesting a more prolonged duration of action. Its increased specificity for respiratory tissue may lead to greater potency with less potential for systemic adverse effects. Fluticasone propionate has been compared with other corticosteroids in animal models for relative topical and systemic potency, and according to these data, it has the most favourable risk-benefit ratio.
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PMID:The pharmacological basis for the treatment of perennial allergic rhinitis and non-allergic rhinitis with topical corticosteroids. 921 61

We studied the activity of a topical form of a corticosteroid (budesonide) and an antihistamine (azelastine) in the treatment of seasonal allergic rhinitis by including an assessment of mediator concentrations and the percentage of eosinophils in the nasal secretions before and after the treatment. Nasal allergen challenge (NAC) during the season was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction. The study compared in a randomized way (2 parallel groups) the effect of budesonide (Rhinocort Aqua) and azelastine (Allergodil nasal spray) in a group of 14 patients during the pollen season. The study showed that azelastine significantly reduced sneezing, total nasal resistance and increased nasal airflow even when significant increases in histamine, tryptase and leukotriene C4 (LTC4) concentrations in nasal secretions were evidenced immediately after NAC. Budesonide showed a strong (p<0.05) decrease in infiltration and activation of eosinophils, and on tryptase and LTC4 release after NAC. These effects (not for LTC4) lasted at least for 1 week after therapy. Azelastine is a powerful topical antihistamine, while budesonide appears to be a potent long-acting anti-inflammatory agent.
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PMID:Effect of topical applications of budesonide and azelastine on nasal symptoms, eosinophil count and mediator release in atopic patients after nasal allergen challenge during the pollen season. 933 13


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