| 124281. |
- Pullerits, Rille, 1969
(författare)
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The inflammatory and immunogenic properties of the receptor for advanced glycation end products and its ligand, high mobility group box chromosomal protein 1
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is a chronic systemic inflammatory joint disease, the pathogenesis of which is complex, involving a wide range of molecules. High mobility group box chromosomal protein 1 (HMGB1) is a nuclear protein recently recognised as a pro-inflammatory cytokine which levels are increased in RA patients. The interaction of HMGB1 with one of its receptors, receptor for advanced glycation end products (RAGE), leads to an inflammatory response. In contrast, the presence of soluble RAGE (sRAGE) has been suggested to function as a decoy by binding RAGE ligands and abrogating cellular activation. The aims of this thesis were to (I) investigate the role of HMGB1 in the development of arthritis; (II) to assess the properties of soluble RAGE in vivo as well as in vitro and to determine the role of sRAGE treatment in HMGB1 triggered arthritis; (III) to determine to what extent sRAGE is present in patients with RA, and to assess the association between sRAGE levels and disease characteristics; (IV) to investigate the immune response to sRAGE in RA patients. To evaluate the role of HMGB1 in arthritis, we administered recombinant HMGB1 into the knee joints of healthy mice. The results demonstrated that HMGB1 triggered joint inflammation. In vitro studies show that sRAGE in contrast to what was previously believed, exerts pro- rather than anti-inflammatory properties giving a dose-dependent rise to production of pro-inflammatory cytokines. Further, we demonstrated that this effect is at least partly triggered by interaction with Mac-1 and mediated via NF-ƒÛB pathway. Intra-peritoneal administration of sRAGE down regulated HMGB1-triggered arthritis, but the observed effect was due to a deviated inflammatory response from joint to peritoneal cavity. Finally, we demonstrated that sRAGE also acted as a chemotactic stimulus for neutrophils in vitro. Matching samples of blood and synovial fluid from RA patients were analysed regarding 1) sRAGE levels and 2) the immune response to sRAGE. RA patients displayed significantly decreased blood levels of sRAGE and higher blood and synovial fluid levels of anti-RAGE antibodies, as compared to healthy controls and patients with non-inflammatory joint disease. The presence of antibodies against sRAGE was associated with a more benign course of RA. Taken together, these results indicate that HMGB1 and sRAGE are pro-inflammatory molecules participating in the development of arthritis. The endogenous antibodies directed against sRAGE might neutralise the pro-inflammatory impact of this molecule, thereby affecting the clinical outcome of arthritis.
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| 124282. |
- Pullerits, Teet, 1967, et al.
(författare)
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Capsaicin cough threshold test in diagnostics
- 2014
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111. ; 108:9, s. 1371-1376
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Tidskriftsartikel (refereegranskat)abstract
- Background: Among patients with chronic unexplained cough, there is a recognized subgroup with respiratory symptoms induced by environmental irritants like chemicals and odours. The diagnosis of sensory hyperreactivity (SHR) has been suggested for this group of patients and can be made using a tidal breathing capsaicin inhalation test. The aim of the present study was to evaluate the ability of a single-breath, dose-response capsaicin threshold test to discriminate such patients from control subjects. Methods: A total of 46 patients with chronic cough and SHR who had previously shown a positive reaction in accordance with limits set for a tidal breathing capsaicin test were tested once with a single-breath, dose-response capsaicin cough threshold test, assessing capsaicin concentrations to evoke 2 (C2), 5 (C5) or 10 (C10) coughs. Twenty-nine subjectively healthy control subjects were also included and tested with the threshold method. Results: Patients had significantly lower C2, C5 and C10 in comparison to controls. From the results among patients and controls, sensitivity and specificity were calculated, and a receiver operating characteristic curve was constructed, showing excellent ability for C5 and C10 to discriminate patients from control subjects. Conclusions: For patients with SHR and chronic cough, capsaicin cough sensitivity was once again confirmed to be increased, in this case, using the single-breath dose-response method. Limits set for cough reactions regarded as more sensitive than normal can be useful in diagnostics and further research. C5 seems to be the best measure to use in research and differential diagnostics.
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| 124283. |
- Pullerits, Teet, 1967, et al.
(författare)
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Comparison of a nasal glucocorticoid, antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis
- 2002
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Ingår i: J Allergy Clin Immunol. ; 109:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Allergic rhinitis requires active intervention for symptom relief. A combination of antileukotriene and antihistamine drugs has been suggested to provide additive treatment benefits for patients with allergic rhinitis. OBJECTIVE: We evaluated how such a combination treatment would affect symptoms and local mucosal eosinophilia in comparison with a nasal glucocorticoid. METHODS: In a double-blind, randomized study 62 patients with grass pollen-induced allergic rhinitis received a nasal glucocorticoid (fluticasone propionate aqueous nasal spray [FPANS], 200 microg/d), an antileukotriene (montelukast, 10 mg/d), a combination of montelukast with an antihistamine (loratadine, 10 mg/d), or placebo throughout the season. Cromoglycate eyedrops and a limited amount of loratadine were allowed as rescue medication for severe symptoms. Patients recorded their symptoms for nasal blockage, itching, rhinorrhea, and sneezing. Before and during the season, nasal biopsy specimens were obtained from patients for evaluation of local eosinophilic inflammation. RESULTS: During the peak season, both FPANS and combined montelukast-loratadine were significantly more effective than placebo and montelukast alone for daytime symptom prevention. For nighttime symptoms, FPANS was significantly more effective compared with all other treatments, whereas combined montelukast-loratadine and montelukast alone did not provide significant symptom prevention compared with placebo. The pollen-induced increase in the numbers of epithelial eosinophils was significantly lower for FPANS-treated patients compared with that seen in all other treatment groups. CONCLUSION: In patients with seasonal allergic rhinitis, intranasal glucocorticoids are more effective than an antileukotriene drug or combined antileukotriene-antihistamine for the reduction of pollen-induced nasal eosinophilic inflammation and for control of nasal symptoms.
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| 124284. |
- Pullerits, Teet, 1967
(författare)
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Cytokine modulation for anti-allergic treatment.
- 2002
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Ingår i: Current pharmaceutical design. - 1381-6128. ; 8:20, s. 1845-53
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Forskningsöversikt (refereegranskat)abstract
- In the complex pathogenesis of airway inflammation seen in asthma, several cytokines are recognized to play a crucial role. Modulation of the effect of these cytokines can provide alternative and more specific treatment approach to currently widely-used systemic immunosuppression by glucocorticoids. Theoretically, cytokine modulation can be achieved via several pathways, including inhibition of released cytokines by using antibodies or soluble receptors, blocking cytokine receptors, inhibiting signal transduction or preventing cytokine gene transcription. Also, some cytokines are known to possess anti-inflammatory effects in allergic inflammation, being thus themselves potentially used as a therapeutic agent. The current review discusses the present knowledge on the involvement of cytokines in the pathogenesis of allergic asthma and the experience on modulation of the effect of these cytokines in clinical situations.
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| 124285. |
- Pullerits, Teet, 1967, et al.
(författare)
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Effect of seasonal allergen exposure on mucosal IL-16 and CD4+ cells in patients with allergic rhinitis
- 2001
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Ingår i: Allergy. - 0105-4538. ; 56:9, s. 871-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: CD4+ T cells constitute a major source of cytokines in allergic diseases such as allergic rhinitis. Interleukin (IL)-16 selectively recruits CD4+ cells. METHODS: We evaluated the effect of natural allergen exposure during a grass-pollen season on IL-16 expression and number of CD4+ cells in nasal mucosa. Patients with allergic rhinitis (n=16) were treated with either a nasal glucocorticoid beclomethasone (BDP; 400 microg/day) or placebo, and gave nasal biopsies prior to and during the grass-pollen season. The evaluated markers in allergic rhinitis patients were also compared to those in healthy control subjects (n=5). RESULTS: Prior to the pollen season, the expression of IL-16, but not the number of CD4+ cells, was significantly higher in patients with allergic rhinitis than in healthy control subjects. The grass-pollen season further increased IL-16 expression and also increased the number of CD4+ cells in placebo-treated, but not in BDP-treated, allergic rhinitis patients. The pollen-season-induced change in IL-16 expression and in CD4+ cells was significantly more pronounced in placebo- than in BDP-treated patients. There was a significant correlation between the change in IL-16 expression and the number of CD4+ cells. CONCLUSIONS: These data suggest that local upregulation of IL-16 expression contributes to the inflammation observed in seasonal allergic rhinitis. Hypothetically, inhibition of IL-16 expression can be one of several mechanisms by which nasal glucocorticoids achieve their anti-inflammatory effect in allergic rhinitis.
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| 124286. |
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| 124287. |
- Pullerits, Teet, 1967
(författare)
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Läkemedelsöverkänslighet
- 2009
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Ingår i: Allergi och astma. Hedlin G & Larsson K, red. Studentlitteratur. - 9789144029962 ; , s. 413-419
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 124288. |
- Pullerits, Teet, 1967, et al.
(författare)
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The duration of bronchodilation of salmeterol and salbutamol as measured by specific airway conductance in healthy subjects.
- 2011
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Ingår i: Pulmonary pharmacology & therapeutics. - : Elsevier BV. - 1522-9629 .- 1094-5539. ; 24:1, s. 55-58
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Tidskriftsartikel (refereegranskat)abstract
- According to the duration of bronchodilation, beta-2-agonists are divided into short and long acting bronchodilators. The bronchodilatory effect of available long acting beta-2-agonists (LABAs) beyond 12h is not sufficiently studied. In order to evaluate the bronchodilatory effects of LABA in subjects without airway obstruction, the measurement of specific airway conductance (sGaw) with whole body plethysmography has been demonstrated to be a sensitive method. We aimed to determine the bronchodilatory effects of single doses of salmeterol 25, 50 and 200μg and salbutamol 200μg in healthy subjects (n=16) over a 24h period in a randomized, double-blind, triple-dummy, placebo-controlled cross-over-study. At the 12-h endpoint, all three doses of salmeterol significantly increased sGaw compared with placebo. At the 24-h endpoint, there was a significant increase in sGaw with salmeterol 200μg, while with 25 and 50μg salmeterol the sGaw increase failed to reach statistical significance. There was no statistically significant increase in sGaw with salbutamol 200μg at either the 12-h or 24-h endpoints. For weighted means, all three salmeterol doses showed statistically significant increase in sGaw compared with placebo over 0-12, 12-24 and 0-24h periods, while for salbutamol 200μg a significant increase in sGaw was recorded only over 0-12h period. We conclude that sGaw measurement is a suitable method for recording the bronchodilatory effect of beta-2-agonists in healthy subjects. Using this method we could demonstrate that salmeterol 200μg provides significant increase in specific airway conductance up to 24h after a single dose.
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| 124289. |
- Pullerits, Teet, 1967, et al.
(författare)
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The triad of current asthma, rhinitis and eczema is uncommon among adults: Prevalence, sensitization profiles, and risk factors
- 2021
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 176
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Tidskriftsartikel (refereegranskat)abstract
- Background Coexistence of asthma, rhinitis, and eczema has been studied in children, but data are lacking in adults. As new treatments emerge, epidemiological data on the coexistence are needed. Aims To study the prevalence of concomitant asthma, rhinitis and eczema in the general adult population and among those sensitized to aeroallergens, and to study associations between background characteristics and risks of phenotypes of asthma, rhinitis, and eczema. Methods In the West Sweden Asthma Study, phenotypes and sensitization profiles of 1103 randomly selected adults (16–75 years) were assessed. The methods included measures of serum-IgE and structured interviews on asthma, rhinitis, eczema, their associated symptoms, and relevant risk factors. Results Among all participants and in those sensitized, 2% and 6% had concomitant asthma, rhinitis, and eczema, respectively, and the condition did not differ by age or sex. Corresponding figures for asthma and rhinitis, but not eczema, was 8% and 19%, respectively. Determinants of coexistence of the three conditions were family history of asthma/allergy, body mass index, and occupational exposure to gas, dust and fumes. Allergic sensitization in those with asthma, rhinitis and eczema was found in 78%, in those with asthma and rhinitis but not eczema in 65%, in those with asthma and eczema but not rhinitis in 40%, while only 5% were sensitized among those having asthma only. Conclusions In the general adult population about 2% have concomitant asthma, rhinitis, and eczema. Of sensitized adults, about 6% has coexistence of the three conditions.
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| 124290. |
- Pullerits, Teet, 1967, et al.
(författare)
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Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during grass pollen season: effect of a local glucocorticoid
- 2000
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Ingår i: Clinical and experimental allergy. - 0954-7894. ; 30:10, s. 1469-75
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Allergic rhinitis is a common disease characterized by infiltration of eosinophils into the nasal mucosa during the periods of symptoms. Among chemokines, which attract cells to the site of inflammation, eotaxin is relatively specific for eosinophils. OBJECTIVE: We examined the influence of grass pollen season on nasal eotaxin expression in patients with seasonal allergic rhinitis, as well as the effect of a nasal glucocorticoid on this eotaxin expression. METHODS: Nineteen patients with allergic rhinitis received treatment with either nasal beclomethasone (400 microgram/day) or placebo over a grass pollen season. In these patients, nasal biopsies were taken prior to and during the peak of the pollen season and stained immunohistochemically for eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave nasal biopsies once prior to the pollen season. RESULTS: Prior to pollen season, there was no significant difference in nasal eotaxin expression between patients with allergic rhinitis and healthy subjects. Grass pollen season induced significant increase in eotaxin expression in placebo-treated (P = 0.04; n = 9) but not in beclomethasone-treated rhinitis patients (P = 0.8; n = 10). During peak grass pollen season, the eotaxin expression in placebo-treated patients was significantly higher compared with healthy subjects outside season (P = 0.03). There was no significant correlation between the expression of eotaxin and the number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in rhinitis patients remained stable over the pollen season. CONCLUSION: Expression of eotaxin in nasal mucosa of grass-pollen allergic rhinitis patients is upregulated during pollen season and treatment with a nasal glucocorticoid protects against this upregulation.
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