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A blog that publishes updates and open access scientific papers about allergy, asthma and immunology. Editor: Juan Carlos Ivancevich, MD. Specialist in Allergy & Immunology
May 12, 2013
The Clinical Usefulness of IgE Antibodies Against Egg White and Its Components in Korean Children
Identification and association of TGFβ-1 expression in patients with asthma in a Polish population - Lodz metropolitan area study
- Int J Biochem Mol Biol >
- v.4(1); 2013 >
- PMC3627069
Int J Biochem Mol Biol. 2013; 4(1): 67–74.
Published online 2013 March 31.
PMCID: PMC3627069
Identification and association of TGFβ-1 expression in patients with asthma in a Polish population - Lodz metropolitan area study
Abstract
Objective: Interaction of genotype and environment results in a specific phenotype of the clinical course of asthma. TGFβ-1 gene belongs to the important group of genes involved in the regulation of proliferation, differentiation, adhesion, and migration of a variety of cell types. TGFβ-1 is inhibitory for B and T cells, as well as IgE production. In particular, it is engaged in inflammation of the bronchi and airway remodeling in asthma, which processes are critical in the pathogenesis of the disease. The aim of this study was to evaluate the correlation between the level of expression of TGFβ-1 and the severity of asthma. Methods: The study included 39 participants (20 healthy subjects and 19 patients with asthma). Each sample was analysed by using real time PCR. Results: There was statistical associations between the control group and the group of patients (p = 0,00007). It was demonstrated strong correlation between healthy and patients with severe asthma according GINA guidelines (p = 0,017). It was found the strong statistical correlation between healthy and patients with severe corticosteroid dependent asthma (p = 0,013). Correlations were observed between levels of asthma severity according to the ATS guidelines and controls. The influence of the level of TGFβ-1 mRNA expression and the severity of asthma (ATS) in the FEV1 (%) parameter value was found. Conclusion: It was found that an important role is played by TGFβ-1 in the pathogenesis of asthma.
Keywords: Asthma, inflammation, airway obstruction, transforming growth factor β-1, T regulatory cells
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Articles from International Journal of Biochemistry and Molecular Biology are provided here courtesy of e-Century Publishing Corporation
Anti-inflammatory effects of clarithromycin in ventilator-induced lung injury
Anti-inflammatory effects of clarithromycin in ventilator-induced lung injury
Laura Amado-Rodríguez, Adrián González-López, Inés López-Alonso, Alina Aguirre, Aurora Astudillo, Estefanía Batalla-Solís, Jorge Blazquez-Prieto, Emilio García-Prieto and Guillermo M Albaiceta
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Respiratory Research 2013, 14:52 doi:10.1186/1465-9921-14-52
Published: 10 May 2013Abstract (provisional)
Background
Mechanical ventilation can promote lung injury by triggering a pro-inflammatory response. Macrolides may exert some immunomodulatory effects and have shown significant benefits over other antibiotics in ventilated patients. We hypothesized that macrolides could decrease ventilator-induced lung injury.
Methods
Adult mice were treated with vehicle, clarithromycin or levofloxacin, and randomized to receive mechanical ventilation with low (12 cmH2O, PEEP 2 cmH2O) or high (20 cmH2O, ZEEP) inspiratory pressures for 150 minutes. Histological lung injury, neutrophil infiltration, inflammatory mediators (NFkappaB activation, Cxcl2, IL-10) and levels of adhesion molecules (E-selectin, ICAM) and proteases (MMP-9 and MMP-2) were analyzed.
Results
There were no differences among groups after low-pressure ventilation. Clarithromycin significantly decreased lung injury score and neutrophil count, compared to vehicle or levofloxacin, after high-pressure ventilation. Cxcl2 expression and MMP-2 and MMP-9 levels increased and IL-10 decreased after injurious ventilation, with no significant differences among treatment groups. Both clarithromycin and levofloxacin dampened the increase in NFkappaB activation observed in non-treated animals submitted to injurious ventilation. E-selectin levels increased after high pressure ventilation in vehicle- and levofloxacin-treated mice, but not in those receiving clarithromycin.
Conclusions
Clarithromycin ameliorates ventilator-induced lung injury and decreases neutrophil recruitment into the alveolar spaces. This could explain the advantages of macrolides in patients with acute lung injury and mechanical ventilation.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production. |
Maresin-1 reduces the pro-inflammatory response of bronchial epithelial cells to organic dust
Research
Maresin-1 reduces the pro-inflammatory response of bronchial epithelial cells to organic dust
Tara M Nordgren, Art J Heires, Todd A Wyatt, Jill A Poole, Tricia D LeVan, D Roselyn Cerutis and Debra J Romberger
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Respiratory Research 2013, 14:51 doi:10.1186/1465-9921-14-51
Published: 10 May 2013Abstract (provisional)
Background
Exposure to organic dust causes detrimental airway inflammation. Current preventative and therapeutic measures do not adequately treat resulting disease, necessitating novel therapeutic interventions. Recently identified mediators derived from polyunsaturated fatty acids exhibit anti-inflammatory and pro-resolving actions. We tested the potential of one of these mediators, maresin-1 (MaR1), in reducing organic dust-associated airway inflammation.
Methods
As bronchial epithelial cells (BECs) are pivotal in initiating organic dust-induced inflammation, we investigated the in vitro effects of MaR1 on a human BEC cell line (BEAS-2B). Cells were pretreated for 1 hour with 0--200 nM MaR1, followed by 1--24 hour treatment with 5% hog confinement facility-derived organic dust extract (HDE). Alternatively, a mouse lung slice model was utilized in supportive cytokine studies. Supernatants were harvested and cytokine levels determined via enzyme-linked immunosorbent assays. Epithelial cell protein kinase C (PKC) isoforms alpha and epsilon, and PKA activities were assessed via radioactivity assays, and NFkappaB and MAPK-related signaling mechanisms were investigated using luciferase vector reporters.
Results
MaR1 dose-dependently reduced IL-6 and IL-8 production following HDE treatment of BECs. MaR1 also reduced HDE-stimulated cytokine release including TNF-alpha in a mouse lung slice model when given before or following HDE treatment. Previous studies have established that HDE sequentially activates epithelial PKCalpha and PKCepsilon at 1 and 6 hours, respectively that regulated TNF-alpha, IL-6, and IL-8 release. MaR1 pretreatment abrogated these HDE-induced PKC activities. Furthermore, HDE treatment over a 24-hour period revealed temporal increases in NFkappaB, AP-1, SP-1, and SRE DNA binding activities, using luciferase reporter assays. MaR1 pretreatment did not alter the activation of NFkappaB, AP-1, or SP-1, but did reduce the activation of DNA binding at SRE.
Conclusions
These observations indicate a role for MaR1 in attenuating the pro-inflammatory responses of BECs to organic dust extract, through a mechanism that does not appear to rely on reduced NFkappaB, AP-1, or SP-1-related signaling, but may be mediated partly through SRE-related signaling. These data offer insights for a novel mechanistic action of MaR1 in bronchial epithelial cells, and support future in vivo studies to test MaR1's utility in reducing the deleterious inflammatory effects of environmental dust exposures.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production. |
May 11, 2013
Efficacy of Anti-Interleukin-5 Therapy with Mepolizumab in Patients with Asthma
RESEARCH ARTICLE
Efficacy of Anti-Interleukin-5 Therapy with Mepolizumab in Patients with Asthma: A Meta-Analysis of Randomized Placebo-Controlled Trials
- Yao Liu,
- Song Zhang,
- Dao-wei Li,
- Shu-juan Jiang ma
Abstract
Background
Interleukin (IL)-5 is believed to be a key cytokine in eosinophil inflammatory infiltration in asthma. Previous clinical trials have evaluated the efficacy and safety of mepolizumab, a monoclonal antibody against IL-5, in patients with asthma. However, most of these studies were small, the conclusions were inconsistent, and the precise effects are therefore debatable.
Methods
A meta-analysis of randomized placebo-controlled trials was conducted to evaluate the effect of intravenous infusion of mepolizumab on clinical outcomes in patients with asthma. Trials were searched in PubMed, Embase, Web of Science, Cochrane CENTRAL, Scopus, reviews, and reference lists of relevant articles. The outcome variables analyzed included eosinophil counts in blood and sputum, airways outcome measures, exacerbations, asthma control, and quality of life scores.
Results
Seven studies met final inclusion criteria (total n = 1131). From the pooled analyses, mepolizumab significantly reduced eosinophils in blood (MD −0.29×109/L, 95% CI −0.44 to −0.14×109/L, P = 0.0001) and sputum (MD −6.05%, 95% CI −9.34 to −2.77%, P = 0.0003). Mepolizumab was also associated with significantly decreased exacerbation risk than placebo (OR 0.30, 95%CI 0.13 to 0.67, P = 0.004), and with a significant improvement in the scores on the Asthma Quality of Life Questionnaire (AQLQ) (MD 0.26, 95% CI 0.03 to 0.49, P = 0.03) in patients with eosinophilic asthma. There were no statistical differences between the groups with respect to FEV1, PEF, or histamine PC20 (all P>0.05), and a non-significant trend for improvement in scores on the Juniper Asthma Control Questionnaire (JACQ) (MD −0.21, 95% CI −0.43 to 0.01, P = 0.06) in the mepolizumab group was observed.
Conclusions
Mepolizumab reduces the risk of exacerbations and improves quality of life in patients with eosinophilic asthma, but no significant improvement in lung function outcomes was observed. Further research is required to establish the possible role of anti–IL-5 as a therapy for asthma.
Citation: Liu Y, Zhang S, Li D-w, Jiang S-j (2013) Efficacy of Anti-Interleukin-5 Therapy with Mepolizumab in Patients with Asthma: A Meta-Analysis of Randomized Placebo-Controlled Trials. PLoS ONE 8(3): e59872. doi:10.1371/journal.pone.0059872
Editor: Hamid Reza Baradaran, Tehran University of Medical Sciences, Iran (Republic of Islamic)
Received: December 1, 2012; Accepted: February 19, 2013; Published: March 27, 2013
Copyright: © 2013 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
Pruritic and Vascular Responses Induced by Serotonin in Patients with Atopic Dermatitis and in Healthy Controls
Pruritic and Vascular Responses Induced by Serotonin in Patients with Atopic Dermatitis and in Healthy Controls
doi: 10.2340/00015555-1473
Authors:
Aram Rausl, Klas Nordlind, Carl-Fredrik Wahlgren
Dermatology and Venereology Unit, Department of Medicine, Solna, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Stockholm, Sweden. E-mail: aram.rasul@ki.se
Dermatology and Venereology Unit, Department of Medicine, Solna, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Stockholm, Sweden. E-mail: aram.rasul@ki.se
Abstract:
Atopic dermatitis (AD) is a chronic inflammatory skin disease with often severe itch. The aim of this study was to determine the pruritogenic and vascular effect of serotonin (5-hydroxytryptamine; 5-HT) in patients with AD and in healthy controls. A 50 µg dose of 5-HT was injected intradermally into non-lesional skin of 25 patients with AD and 25 healthy control individuals, and the effect compared with 0.2 µg histamine as a positive control, and buffer as a negative control. Pruritus was recorded by the subjects, using a computerized visual analogue scale, while flare and wheal were recorded by the investigator. There was no qualitative or quantitative difference in 5-HT-induced itch between patients and control subjects, or between males and females. However, reduced flare and wheal were found in the patient group for 5-HT. There were no correlations between clinical findings (i.e. eczema severity, clinical pruritus) and recorded experimental itch, or flare or wheal responses for 5-HT, in the patients with AD. In both groups a shorter itch latency was found for 5-HT compared with histamine. Through the use of intradermal injections, making it possible to calculate the dose of substance delivered, a lower vascular response to 5-HT was shown in patients with AD compared with healthy controls. In addition to confirming a pruritogenic role of 5-HT in both patients with AD and healthy controls, we found a shorter itch latency for 5-HT compared with histamine in both groups. The short itch latency time may indicate a direct effect of 5-HT on itch receptors.
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Early nutrition in the prevention of allergic disease: A survey of general paediatricians and dietitians in Atlantic Canada
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Critical appraisal of bilastine for the treatment of allergic rhinoconjunctivitis and urticaria
Critical appraisal of bilastine for the treatment of allergic rhinoconjunctivitis and urticaria
Review
(511) Total Article Views
Authors: Sadaba B, Azanza JR, Gomez-Guiu A, Rodil R
Published Date May 2013 Volume 2013:9 Pages 197 - 205
DOI: http://dx.doi.org/10.2147/TCRM.S16079
| Received: | 04 March 2013 |
|---|---|
| Accepted: | 05 April 2013 |
| Published: | 03 May 2013 |
Clinical Pharmacology Service, Clinica Universidad de Navarra, Navarra, Spain
Abstract: Bilastine is a second generation antihistamine indicated for the treatment of seasonal or perennial allergic rhinoconjunctivitis and chronic urticaria with a daily dose of 20 mg, in adults and children over 12 years of age. The efficacy of bilastine has been shown to be similar to that of the comparator drugs for the control of the nasal and nonnasal symptoms of allergic rhinoconjunctivitis, while also showing a subjective improvement in the quality of life and in overall clinical impression. For chronic urticaria the symptoms (itching and the development of papules) lessens from the second day of treatment onwards, in a similar way to other antihistamines used as comparators. Bilastine should not be administered at meal times to avoid interference with the absorption process. It is not distributed to the central nervous system, is scarcely metabolized, and elimination is through the kidneys and feces, with a 14-hour elimination half-life. It has no effect on cytochrome P450. During clinical development, bilastine was shown to be a drug that is adequately tolerated, with a similar effect to placebo with regard to drowsiness and changes in heart rate. In relation to its use, headaches were the most frequent adverse effect to be reported. No cardiotoxic effects have been observed, and the therapeutic dose does not alter the state of alertness.
Keywords: bilastine, allergic rhinoconjunctivitis, chronic urticaria, second generation antihistamine, drowsiness, CYP450
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