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  • 1
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The neurotrophins Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin (NT)-3 are produced, stored and released by various immunological cells. The influence of NTs upon the function of these cells is described. Elevated plasma levels were found in inflammatory, autoimmune and allergic diseases with the highest levels in allergic asthma. A connection between bronchial hyper-responsiveness and serum levels has been reported.Objective Little is known about the influence of treatment with inhaled corticosteroids (ICS) on serum NT levels and their influence on the asthmatic state.Methods Eighty-seven volunteers were studied. Thirty-eight were stable allergic asthmatics with constant ICS doses, 29 were asthmatics not receiving anti-asthmatic treatment and 20 were age- and sex-matched healthy controls. Demographic and lung function data were evaluated. NT serum levels were determined by ELISA.Results NGF and BDNF levels were significantly increased in untreated asthmatics compared to the control and the treated group, while NT-3 demonstrated significantly higher levels in treated asthmatics compared to healthy controls. After stabilization of untreated subjects with ICS, the NT levels decreased significantly.Conclusions These results suggest that NTs participate in allergic inflammation and asthma. Effective treatment leads to a decrease of circulating neurotrophic factors.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Allergic rhinitis (AR) is the most common allergic disease affecting the respiratory tract. Next to inflammatory changes, the airway innervation plays an important modulatory role in the pathogenesis of the disease.Objective To examine the participation of different neuropeptides in the human nasal mucosa of intermittent (seasonal) AR tissues in the allergic season.Methods Immunohistochemistry for substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide tyrosine (NPY) was related to the characterization of inflammatory cells in tissues of patients with seasonal AR (n=18).Results While there was a significant increase in the number of eosinophils present if compared with a control group, no changes occurred in mast cell numbers. Immunostaining was abundantly found in different nerve fibre populations of both groups. SP expression was significantly increased in mucosal nerve fibres of patients with intermittent (seasonal) AR. Also, significantly increased numbers of VIP- and NPY-immunoreactive nerve fibres were found in biopsies of rhinitis patients in comparison with sections of normal human nasal mucosa. In contrast, CGRP expression did not change significantly.Conclusion The increase of neuropeptide expression in mucosal nerve fibres indicates a major role of the autonomous mucosal innervation in the pathophysiology of intermittent (seasonal) AR.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Recent studies have shown that neurotrophins are produced by and can act on several immune-inflammatory cells. The origin of circulating as well as local neurotrophins is unknown.Objectives The aim of this study was to assess whether eosinophils of allergic and non-allergic donors produce, store and release the neurotrophic factors NGF, BDNF and NT-3.Methods Eosinophils were purified by negative immunoselection (purity 〉 96%) from allergic asthmatics and non-allergic donors (25 to 53 years). The presence of mRNA for neurotrophic factors was evaluated by reverse transcription PCR. Specificity was demonstrated by cloning products and sequencing. Stored NGF, BDNF and NT-3 was demonstrated by Western-blotting and flow cytometry. Eosinophils were incubated and supernatants were collected for measurement of neurotrophic factors after cell stimulation with PAF. Neurotrophin content in eosinophil lysates was determined by ELISA.Results Eosinophils demonstrate mRNA for neurotrophins. Proteins were detectable by Western blot and FACS analysis. Neurotrophins were found in the eosinophil lysates at different amounts comparing allergic and non-allergic donors. Cell stimulation with PAF (10-8–10-5 M) after priming with GM-CSF leads to a dose-dependant release of NGF and BDNF.Conclusions Eosinophils store, produce and release NGF, BDNF and NT-3. They are a possible source of elevated neurotrophin levels found in allergy and asthma.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Recent studies have shown that nerve growth factor (NGF) can act on several immune cells as well as residential cells. But little is known about their role in modulating eosinophil function via activation of high-affinity receptors.Objectives The aim of this study was to assess whether eosinophils express functional receptors and if their function is influenced by NGF, brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3).Methods Eosinophils were purified by negative immunoselection (purity 〉 96%). High-affinity neurotrophin receptors were demonstrated by reverse transcription polymerase chain reaction, western blotting and flow-cytometry analysis. Functionality of receptors was demonstrated by receptor phosphorylation after ligand binding. Eosinophils were incubated with NGF, BDNF and NT-3, and cells and supernatants were collected for measurement of the mediators IL-4, IL-5, IL-8, transforming growth factor (TGF)-β1, eosinophil cationic protein (ECP), eosinophil protein X (EPX) as well as eosinophil viability.Results Eosinophils expressed mRNA for neurotrophin receptors. Proteins were detectable by western blot and fluorescent-activated cell sorter analysis. The receptors were phosphorylated after stimulation with neurotrophins. After NGF stimulation, a significant increase in IL-4 was detectable. BDNF and NT-3 stimulation led to a significant increase in EPX. Eosinophil viability was not influenced.Conclusions Eosinophils express the functionally active receptors TrkA, TrkB and TrkC. Receptor activation stimulates eosinophils. This might be an additional pathway regulating inflammatory responses in allergic reactions.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Blomia tropicalis is a common mite found in the house dust of many tropical countries including Venezuela. The prevalence of skin test and specific serum immunoglobulin (Ig)E reactivity to B. tropicalis in Venezuela has not been previously evaluated.Methods:  In the present study we evaluated the skin reactivity by skin prick test and specific IgE by a multiple antigen blot assay, against B. tropicalis and Dermatophagoides pteronyssinus, in a group of 115 subjects who attended the Allergy Clinic of the Institute of Biomedicine, Caracas, Venezuela, and we studied possible cross reactions between similar proteins of these two mites.Results:  One hundred and six patients with persistent allergic respiratory symptoms showed a positive skin prick test to at least one of the mite extracts, with the frequency of positive reactions to B. tropicalis being as high as to D. pteronyssinus. Twelve patients reacted only to D. pteronyssinus and 13 different patients only to B. tropicalis. Specific IgE to each of the mite extracts was found with similar frequency, and the results coincided with the skin test reactivity.Conclusions:  The study indicated the importance of including B. tropicalis in routine diagnostic testing in tropical and sub-tropical situations.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1420-908X
    Keywords: Key words:Neuropeptides - Substance P - Allergic rhinitis - Histamine release - Nasal mucosa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Objective and Design: There is evidence that substance P (SP) is involved in events related to allergic and non-allergic rhinitis. Furthermore, some effects of SP seem to be greater in subjects suffering from allergic rhinitis than in non-allergic subjects. To investigate if these effects may be partly mediated by histamine release (HR) we studied the influence of SP on HR from nasal mucosa of subjects with and without allergic rhinitis using an in vitro organ culture system.¶Subjects: Nasal mucosa of the inferior turbinate was obtained from ten patients suffering from allergic rhinitis and eighteen non-allergic subjects receiving surgical therapy for nasal obstruction.¶Methods: Tissue samples of nasal mucosa were stimulated with 10-5 M SP or with 10-5 M Ca-ionophore A23187 for 120 minutes, and the histamine content was determined in the culture supernatant.¶Results: Both SP and Ca-ionophore A23187, caused a significantly higher HR from the samples of the non-allergic group (p〈0.01) compared to baseline controls (spontaneous release). The same effect was seen in the allergic group (p〈0.01 and p=0.036). Comparing the increase in HR from allergic and non-allergic mucosa, in allergics the HR stimulated by SP was significantly higher (p=0.031), whereas Ca-ionophore A23187 did not show this effect.¶Conclusion: These findings suggest a role of SP in inducing release of histamine from human nasal mucosa, thereby influencing physiologic and pathophysiologic nasal conditions, especially in allergic inflammatory processes.¶
    Type of Medium: Electronic Resource
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