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)

In a double-blind, parallel-group study, we examined the effect of short-term treatment with inhaled fluticasone propionate (FP) in a group of 20 nonsmoking asthmatic patients who required only beta2-agonists to control their symptoms. We administered FP (250 microg twice daily) or matched placebo for 6 wk. Methacholine challenge was performed before treatment, after 3 wk, and at the end of treatment. Each patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy before and after treatment. Eight patients in the placebo group and nine patients in the FP group completed the study. Bronchial responsiveness to methacholine decreased significantly only after 6 wk of treatment with FP (p < 0.05). When we compared the FP group with the placebo group, we observed a significant decrease only in the number of cells expressing intracellular adhesion molecule-1 (ICAM-1) and MAC-1 (p < 0.04 and p < 0.03, respectively). Moreover, we saw that the tryptase level in BAL decreased (p < 0.001), whereas the eosinophil cationic protein (ECP) level did not change significantly. Additionally, the number of eosinophils and mast cells in the lamina propria in bronchial biopsies specimens was significantly smaller in the FP group than in the placebo group (p < 0.02 and p < 0.01, respectively). Additionally, in the FP group, we found that basement-membrane thickness was significantly decreased when compared with that of the placebo group (p < 0.05). In conclusion, our results show that short-term treatment with low-dose FP reduces inflammatory cell infiltration into the lamina propria in bronchial biopsy specimens. Moreover, short-term low-dose FP treatment might control the intensity of airway remodeling in mild asthma.
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PMID:Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlled study. 919 87

Six healthy non-atopic male volunteers participated in a dose-response study of N,N-dimethylbenzylamine (DMBA), which is a reactive chemical used in epoxy systems. The effects on the nasal mucosa after inhalation of 0, 20, 45, 80 and 120 microg/m3 were studied by means of symptom recordings, acoustic rhinometry, nasal lavages and nasal cytology processed for light microscopy of metachromatic cells (MC) and eosinophils (EOS). Although only minor symptoms were provoked, the numbers of MC and Eos tended to increase in a dose-response fashion after inhalation of the chemical. No signs of degranulation of the cells were found, as the levels of tryptase and eosinophil cationic protein in the nasal lavages remained low at all DMBA exposure levels. We therefore conclude that a reactive chemical such as DMBA can influence MC and Eos in the nasal mucosa even at low dose levels without causing significant clinical symptoms.
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PMID:Metachromatic cells and eosinophils in the nasal mucosa and N,N-dimethylbenzylamine exposure. 919 31

Although Type I allergy is a trigger for provoking chronic inflammation, whether allergic sinusitis (AS) can be distinguished from sinusitis due to chronic infection is still debated. This study was performed to characterize inflammatory cells in AS and to determine whether patients with AS differ from patients with chronic suppurative sinusitis (CSS). 5 patients with AS and 10 patients with CSS were investigated. Cellular infiltration was studied using immunohistochemistry with monoclonal antibodies using CD3, CD4, CD8, CD25, major basic protein (BMK13), eosinophil cationic protein (EG2), neutrophil elastase, and tryptase. There were no differences in CD3+, CD4+, CD25+, and tryptase+ cells between the groups. Whereas the total number of eosinophils (BMK13+) also did not significantly differ, the number of activated eosinophils (EG2+) was significantly higher (P < 0.05) in patients with AS. Furthermore, a statistically significant increase in the percentage of activated eosinophils to total eosinophils (P < 0.05) was observed in patients with AS. In contrast, the number of neutrophil elastase+ cells was significantly higher (P < 0.05) in patients with CSS. These results suggest that patients with AS can be distinguished immunohistochemically from patients with CSS, with AS being distinguished by activated eosinophil infiltration.
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PMID:Preferential infiltration by activated eosinophils in allergic sinusitis. 925 57

Ketotifen is marketed throughout the world as an antiallergy drug, but whether it affects infiltration of inflammatory cells into airway mucosa is not known. We studied the effects of ketotifen on symptoms, pulmonary function, and airway inflammation in 25 patients with atopic asthma. Patients took ketotifen (1 mg twice daily) or a matching placebo for 8 weeks in a double-blind, parallel-group study. Data recorded on diary cards were used for 2 weeks before treatment began, and they were used for the last 2 weeks of treatment to study asthma symptoms, use of beta 2-agonists, and peak expiratory flow (PEF). Pulmonary function tests, bronchial responsiveness to methacholine, and fiberoptic bronchoscopy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. Specimens were stained immunohistochemically with monoclonal antibodies against stored eosinophil cationic protein (EG1), the secreted form of eosinophil cationic protein (EG2), mast-cell tryptase (AA1), neutrophil elastase (NP57), CD3, CD4, CD8, and CD25. The numbers of positively stained cells in the lamina propria were counted. Compared with the placebo, the ketotifen-treated group exhibited significant improvement of asthma symptoms (P < 0.05) and bronchial responsiveness (P < 0.05). This was accompanied by a reduction of EG2+ eosinophils (P < 0.05), CD3+ T cells (P < 0.001), CD4+ T cells (P < 0.01), and CD25+ activated T cells (P < 0.01) in the bronchial mucosa. These results suggested that the beneficial effects of ketotifen in bronchial asthma may result from consequent inhibition of activated eosinophils and T-cell recruitment into the airway. Moreover, ketotifen may relieve allergic inflammation in bronchial asthma.
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PMID:Effects of ketotifen on symptoms and on bronchial mucosa in patients with atopic asthma. 928 80

1. Although mast cell hyperplasia is a feature of rheumatoid arthritis and osteoarthritis, the extent and nature of mast cell activation in joint disease have not been clearly established. 2. We have investigated the levels of mast cell tryptase and histamine and also of eosinophil cationic protein in synovial fluid collected from 31 patients with rheumatoid arthritis, 14 with seronegative spondyloarthritis and nine with osteoarthritis. Two RIAs for tryptase were employed: one with monoclonal antibody AA5, which was found to bind equally well to both alpha and beta isoforms on Western blots of the recombinant enzyme, and the other with antibody G5, which recognizes predominantly beta-tryptase. 3. alpha-Tryptase, which is likely to be released constitutively from mast cells, appeared to be the major form in synovial fluid, as the assay with antibody AA5 detected appreciably more tryptase than that with antibody G5. beta-Tryptase, which is released on anaphylactic activation of mast cells, was detected in 14 out of 45 synovial fluid samples studied, with concentrations of up to 12 micrograms/l measured by the G5 assay. The apparent levels of beta-tryptase, but not of alpha-tryptase, were closely correlated with those of histamine in the synovial fluid. Patients with osteoarthritis appeared to have a greater proportion of beta-tryptase in the synovial fluid than those with rheumatoid arthritis, as well as higher concentrations of histamine. Eosinophil cationic protein was present at high levels in the synovial fluid, although eosinophil numbers were low, and its concentrations were not correlated with the concentrations of the mast cell products. 4. These data suggest that anaphylactic degranulation of mast cells may have occurred to a greater extent in osteoarthritis than in rheumatoid arthritis, despite the relative lack of synovial inflammation in osteoarthritis. Although the eosinophil cationic protein detected may not reflect eosinophilic inflammation in the joint, the presence in synovial fluid of tryptase of both major forms, and of histamine, appears to indicate that mast cell products are secreted constitutively, as well as by processes of anaphylactic degranulation in rheumatoid arthritis, seronegative spondyloarthritis and osteoarthritis.
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PMID:Mast cell activation in arthritis: detection of alpha- and beta-tryptase, histamine and eosinophil cationic protein in synovial fluid. 940 29

Our purpose was to determine if the study of rhinitis is useful in the diagnosis of asthma. We formulated the hypothesis that the inflammation of the upper airway reflects the inflammation of the lower airway. It was found that there are allergens that produce rhinitis more frequently than asthma, and vice versa. This can be explained by size. This explanation, however, is questionable as the allergic proteins are extracted from the carrying agent, and through the lymphatic route or the blood, reach the entire human organism. It was also found that with bronchoalveolar lavage in allergic asthma it is possible to obtain the same results for eosinophils as with a nasal wash or using Citospyn. However, the results in the late phase are questionable. In the immediate phase and in the late phase, eosinophil cationic protein (ECP) was detected in the blood (in asthma) and in nasal washes (in rhinitis). In the immediate response tryptase was detected from the mast cells. The role of leukotrienes in asthma and rhinitis is well established in the early and late response. The use of leukotriene inhibitors guarantee their importance in the airway. Platelet-activating factor (PAF) has been demonstrated to increase vascular permeability and the use of antagonists were the best nasal feature. The inhalation of histamine caused bronchospasm, while instillation of histamine in the nasal passages increased resistance. With this information it seems that our hypothesis has been confirmed. Rhinitis and BHR together are equivalent to asthma, although the PFER decreases during the course of nasal provocation test (NPT) in nonasthmatic patients. In pure rhinitis patients, however, we find decreases in PFER due to effort. All this suggests that the study of nasal inflammation is still unclear with regard to bronchial inflammation.
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PMID:Rhinitis and asthma: nasal provocation test in the diagnosis of asthma. 941 59

Nasal allergen challenges, despite not reproducing exactly natural allergen exposure, are a very useful method to understand the complex cellular kinetics and cellular interactions that occur in allergic rhinitis. Cell-specific soluble mediator measurements can give useful diagnostic information. In this paper we present data concerning eosinophil cationic protein (ECP) and tryptase measurements after nasal allergen challenge.
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PMID:Nasal allergen challenge and mediators release. 943 23

Ten patients with perennial allergic rhinitis and 10 healthy subjects were studied to determine most discriminative nasal irrigation fluid marker(s) and to compare samples that were collected at baseline and over a 1-hour period, every 15 minutes. The latter were pooled and designated 1-hour sample. In the nasal irrigation we investigated the following inflammatory cells and soluble mediators: eosinophils, neutrophils, granulocyte-macrophage colony-stimulating factor, interleukin-4, interleukin-6, interleukin-8, ECP, EPX, MPO, leukotriene C4, leukotriene B4, prostaglandin E2, tryptase and fibrinogen. Patients with PAR were then treated for 2 weeks with the topical nasal steroid. The only marker that discriminated patients with perennial allergic rhinitis and healthy subjects was eosinophil count (EO%): correspondingly 14.01 +/- 5.8 and 0.18 +/- 0.09, (M +/- SD). Difference between the studied groups did not depend on the time of irrigation, baseline or 1-hour. EO% was also the only marker of a clinically successful treatment with the nasal steroid, 14.01 +/- 5.8 and 0.87 +/- 0.4, before and after treatment respectively. We conclude that EO% is the most sensitive inflammatory marker of perennial allergic rhinitis, and that baseline nasal irrigation can be used to study nasal mucosal inflammation.
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PMID:Clinical and nasal irrigation fluid findings in perennial allergic rhinitis. 943 56

This study investigated the early, prolonged immediate, and late-phase reactions of dust-mite-sensitive subjects undergoing long-term challenge in the Vienna challenge chamber (VCC) in terms of clinical symptoms and inflammatory mediator level patterns in nasal lavage fluids. A concentration of 70 ng Der p 1/m3 of air (feces of Dermatophagoides) was maintained over 8 h in the VCC. To show the clinical impact of this challenge model, the effect of a histamine H1-receptor antagonist that also has some antiallergic properties (loratadine) was also investigated. The study followed a double-blind, placebo-controlled, crossover design. Medication was given orally over 7 days before the provocation at a dose of 10 mg once daily. All 12 patients, whose dust-mite sensitivity was confirmed by disease history, skin prick test, and RAST, completed the challenge session. The documentation of the chosen parameters was performed every 30 min. Subjective nasal and ocular symptoms were assessed via a visual analog scale of 100 mm, nasal flow was recorded by active anterior rhinomanometry, and mediator release was evaluated with nasal lavages. Clinical aspect: the whole sample population showed a rise of nasal and ocular symptom severity and a nasal flow reduction, which were perceptibly, but not significantly attenuated by active drug treatment. Mediator pattern: in each patient, prostaglandin (PG)D2 and leukotriene (LT)C4 levels peaked within the first 2 h of provocation, PGD2 then moving toward baseline levels, and LTC4 then again rising continuously. Eosinophil cationic protein (ECP) exhibited a constant level increase over the whole provocation period, and tryptase levels did not change significantly. Whereas the area under the curve values of tryptase and ECP were higher in drug-treated patients than the placebo group, the early PGD2 peak occurring during the first two challenge hours seemed to be mitigated by loratadine. These results reveal that there is no link between the clinical symptoms, the drug efficacy, and the released mediators (LTC4, PGD2, ECP, and tryptase).
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PMID:Effect of continuous allergen challenge on clinical symptoms and mediator release in dust-mite-allergic patients. 949 Dec 31

Airways inflammation markers may help in predicting prognosis, in diagnosis and in monitoring respiratory diseases. Inflammation markers specific for certain cells may indicate the nature of the inflammatory processes, whilst others indicate stage and intensity. Intercellular adhesion molecule 1 (ICAM-1) helps to establish contact between the antigen-presenting cell and T-lymphocytes. Soluble serum ICAM-1 is increased in developing chronic lung disease of the newborn and atopic bronchial asthma. ICAM-1 is also the major human rhinovirus receptor. Interleukin 4 and interferon-gamma regulate the immunoglobulin E response, are difficult to measure in serum, and most groups employ stimulated cell cultures. These early inflammation markers may have predictive value. The leukotrienes are released from mast cells and eosinophils. Leukotriene (LT) B4 may be analysed in serum, whereas the cysteinyl leukotrienes, LTC4, LTD4, LTE4, may be assessed in urine. Serum LTB4 and urinary LTE4 have been found to be elevated during acute wheezy exacerbations. Tryptase is released from mast cells and is elevated in serum during acute anaphylaxis. However, tryptase has not been found to be related to inflammatory activity under other conditions. Myeloperoxidase is released from neutrophils, and serum levels are elevated in asthma, respiratory infections and other chronic lung diseases. The eosinophil markers eosinophil cationic protein (ECP) and eosinophil protein X (EPX) reflect eosinophil activation. ECP in serum and EPX in urine are elevated in asthma, atopic eczema and other conditions with eosinophil activation. They are related to symptom activity in asthma and atopic eczema and are influenced by anti-inflammatory therapy. In early wheezing, serum ECP may have predictive value. Serum ECP is dependent upon sampling procedures. Nitrogen oxide in exhaled air reflects inflammatory activity in asthma, and is influenced by anti-inflammatory therapy. However, in young children there are sampling difficulties.
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PMID:Markers of airway inflammation in preschool wheezers. 951 Jun 66


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