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Andrzej M Fal

Publications and source records attributed to Andrzej M Fal.

11 recordsLinked to original sources

Intracellular signaling pathways in IgE-dependent mast cell activation.

Mast cells (MCs) are both central effectors and signaling cells in allergic reactions. Their key role in the immunopathology of asthma and other allergic diseases has been well documented. Molecular events leading to MC activation have not been yet fully established, however. Recent studies emphasize the key role of the protein tyrosine kinases Lyn and Fyn in MC signal transduction. The finding that Lyn kinase negatively regulates MC degranulation and that Fyn kinase enhances this effector response is of great importance. This creates new possibilities for therapeutic intervention in asthma and other allergic diseases. This review summarizes current knowledge on MC intracellular signaling and discusses the most recent strategies for the treatment of allergic diseases based on MC signaling pathway inhibition.

Animals↗

[Antieosinophil action of IL-12 in human polyp culture].

RATIONALE: Tissue eosinophilia is an important pathophysiological issue in bronchial asthma and nasal polyps. Its magnitude is regulated by several mechanisms, including selective migration of eosinophils to peripheral tissues and prolongation of survival. A key role in this processes is assigned to Th2 originating cytokines: IL-3, IL-5, GM-CSF. It has been previously demonstrated that IL-12 diminishes tissue eosinophilia in an animal model, and Hofstra showed that IL-12 together with IL-18 prevents allergen-induced increase bronchial hyperresponsiveness, BAL eosinophilia and the development of allergen-specific Th2 cells. METHODS: Nasal polyps were obtained during routine surgery and were cultured in fragments of approximately 30 mg for 2, 6, and 15 days in RPMI 1640 in the absence or presence of IL-12. Afterwards a dose-dependency was tested at day 2 of culture. Polyp tissue from cultures was than processed to slides, stained with Giemsa and cells were counted in light microscopy (400x). RESULTS: Eosinophils represented 62.8+/-21.3% of residing cells in nasal polyps at the day 0. IL-12 (1 microg/ml) caused a significant time-dependent decrease in the percentage of Eos after 2 and 6 days. The effect of IL-12 at day 2 was concentration-dependent: control, 28.2+/-2.9; at 10 ng/ml, 13.9+/-6.4 (n=4, p<0.05); at 100 ng/ml, 11.6+/-2.1 (p<0.01); at 1 microg/ml, 7.5+/-1.5 (p<0.005). CONCLUSION: IL-12 acts as potent topical antieosinophilic agent. Its action can be seen in a cultured polyp environment. It is visible already after two days and is concentration-dependent. Further study is needed to elucidate tissue mechanisms of this action.

Adult↗

[Use of selected parameters of nasal lavage fluid in asthma severity monitoring].

UNLABELLED: Allergic inflammation is a chronic disorder underlying asthma and allergic rhinitis. There is a theory "one system--one disease" connecting these two atopic diseases. Eosinophil is a major effector cell in both processes. The possible correlations between spirometric parameters and concentrations of selected mediators in peripheral blood and nasal lavage (NLF) fluid were estimated. 14 asthmatic patients entered the study, all of them symptoms free. In NLF supernatants and in blood ECP and sVCAM-1 concentrations were measured and cells in NLF were counted. RESULTS: Number of eosinophils in NLF correlated with sVCAM-1 concentration in NLF (R2 = 0.68; p < 0.05). In serum ECP and sVCAM-1 concentrations correlated with each other (R2 = 0.73; p < 0.05). Correlation between ECP concentration in serum or NLF and FEV1 was: R2ser = 0.49, R2NLF = 0.50 (p < 0.05), respectively. ECP concentration concentration correlated in serum and NLF correlated with MEF25: R2ser = 0.77, R2NLF = 0.45 (p < 0.05), and sVCAM-1 spirometric parameters: R2FEV1 = 0.26, R2MEF25 = 0.67, p < 0.05. CONCLUSION: VCAM-1 is active in selective eosinophil migration to peripheral tissue. It can also activate these cells. Concentration of ECP and sVCAM-1 in blood serum and NLF correlate with the course of bronchial asthma described by spirometric parameters, and therefore can be used in disease treatment monitoring.

Adult↗

[Allergy to mould allergens as a risk factor for bronchial asthma in patients suffering from allergic rhinitis].

UNLABELLED: The ARIA study demonstrates the correlation between bronchial asthma (BA) and perennial rhinitis (PR) with mite or animal fur allergies. There are no reports concerning correlation between BA and PR with mould allergy. The authors of this study estimated the prevalence of BA in patients with PR, allergic to moulds in comparison with patients allergic to other aeroallergens. 460 patients suffering from PR were investigated: 102 were allergic to moulds (mono- or multisensitization type) and 358 were allergic to other allergens. The prevalence of BA in mould-sensitive and insensitive patients was 70.6% and 43.6%, respectively; it was significantly higher in the mould-sensitive group (p = 0.004) regardless of the type of mould hypersensitivity (mono- or multisensitization). The higher prevalence of BA in mould-sensitive patients was found to be valid only for adults. The adult PR patients with diagnosed BA were most frequently allergic to Alternaria (47.1%) and Cladosporium (30.8%). IN CONCLUSION: mould allergy may be a risk factor for BA development.

Adolescent↗

[Cytokines and anti-cytokines in allergic diseases].

Allergic inflamation is complexed phenomenon related to the activity of many mediators released from "effector cells". The role of IL-12, IL-5, IL-4 and some adhesive molecules is presented with special attention focused on therapeutical aspects in allergic diseases.

Anti-Allergic Agents↗

[Mechanisms of action of nebulized low molecular weights heparin in patients with bronchial asthma].

Bronchial asthma is a chronic disease of the respiratory tract. Search for alternative to presently used therapies seems to be the way to obtain a better control of asthma. Heparin is an acidic mucopolysaccharide and in the past years there has been a number of reports on the role of heparin and low-molecular-weight heparin (LMWH) in chronic inflammatory disorders of the respiratory tract. Our aim was to estimate the effect of long-time LMWH nebulization on selected parameters in asthmatic patients. Twenty-four patients entered the study. All of them were subjected to bronchoscopy with BAL, in 8 patients this procedure was performed twice: before and after heparin treatment. After 14 days of treatment we observed an increase in FEV1 (from 73.93 +/- 14.14% (in % of nominal value) to 89.62 +/- 10.08% (p = 0.0049). Additionally we noted a decrease in the percentage of eosinophils and lymphocytes in BAL sediments, from 4.86 +/- 3.48% to 1.25 +/- 2.76%; p = 0.0006 and from 5.39 +/- 2.25% to 2.94 +/- 1.23%; p = 0.0209, respectively. This changes were paralleled by a drop of EG2 in BAL supernatant from 1.00 +/- 0.99 to 0.13 +/- 0.35, p = 0.0256. In blood serum level of histamine 0.74 +/- 0.77 to 0.1 +/- 0.22; p = 0.0493. We did not observe significant changes in IL-5, sVCAM-1 or ECP concentrations in serum. Also different LMWH dosing (5-10 kUIC anti-Xa b.i.d.) did not produce any dose-response effect. We conclude, that LMWH in nebulization can be a valuable add-on treatment in bronchial asthma, and its most likely mechanisms of action are: prevention of mast cell degranulation (histamine decrease), decreased eosinophil activation (lower EG2), and modification of inflammatory cells influx (decreased percentages of eosinophils and lymphocytes in BAL).

Adult↗

Latex allergy and sensitization in children with spina bifida.

BACKGROUND: The purpose of this study was to investigate the prevalence rate of latex sensitization and latex allergy among children with spina bifida and to evaluate risk factors for natural rubber latex hypersensitivity. METHODS: A total of 34 children between 2.5 and 17 years of age participated in the study. Participants completed a questionnaire and underwent skin prick tests with latex, common aeroallergens and food allergens as well as measurements of specific IgE to latex and food allergens (RAST CAP). RESULTS: The prevalence of latex sensitization and latex allergy was estimated to be 32.4 and 18.8%, respectively. The most common reported clinical manifestation of latex allergy was urticaria. Three out of six symptomatic patients reported anaphylactic reactions. CONCLUSION: We found that major risk factors for latex sensitization were atopy and a history of numerous operations.

Adolescent↗

[The influence of a three-year preseasonal specific immunotherapy on selected parameters of allergic inflammation in pollinosis patients].

Specific immunotherapy (SIT) can in some cases influence the course of allergic inflammation (eosinophilia and ECP concentration in peripheral tissue). This study was set up to evaluate the efficacy of three-year pre-seasonal SIT with grass pollen allergoid. We measured NALf eosinophilia and ECP concentration both in NALf and blood serum after subsequent SITs. Twenty seven patients aged 26.7 +/- 7.4 (range 18-45) entered this study. They were randomly assigned to treatment with either Pollinex or Allergovit. We observed a progressive fall in NALf eosinophilia in subsequent years: 24.1 +/- 2.4%; 20.2 +/- 4.6%; 9.8 +/- 1.9% vs. 30.4 +/- 3.0% before treatment (p < 0.05, p < 0.05 and p < 0.001, respectively). Also ECP concentration fell after second and third SIT to 15.6 +/- 1.5 ng/ml i 12.96 +/- 1.75 ng/ml vs 23.3 +/- 3.7 ng/ml before SIT (p < 0.05). A significant drop in serum ECP concentration was recorded only after the third SIT season--2.5 +/- 1.23 micrograms/ml vs 5.8 +/- 1.3 micrograms/ml before treatment, p < 0.01. NALf eosinophilia correlated positively with NALf ECP concentration--R2 = 0.92, p < 0.05. Hence, SIT ameliorates allergic inflammation decreasing significantly activity of eosinophils in nasal mucosa measured as NALf eosinophilia and ECP concentration. This effect seems to be time-depended.

Adult↗