This study highlights the significance of monitoring cardiac functions in newborns with HIE. ECG changes and serum Troponin I level at 72 h after birth are likely to have significant predictive value in the assessment of mortality in HIE. Further studies will provide additional data for the long-term prognostic value of cardiac functions in this disorder.

IL-5 levels, as a marker of eosinophilic inflammation, were demonstrated to be higher in the children with atopic asthma when compared to those with nonatopic asthma in EBC. The fact that no significant difference was apparent in the IL-8 levels between the groups suggests that it is the severity of the disease rather than the atopic state that plays an important role in IL-8 levels. Since no difference was recorded between the groups in terms of MMP-9 levels, lung damage in asthma sufferers seems to develop independent of atopia.

Along with the determination of the diagnostic values of communities, the rapid and accurate diagnosis of the children with a food allergy will be ensured, and the patient follow-up will be made easier.

Airway epithelium plays an important role as a physical barrier and a modulator of allergic response. Junctions between cells provide epithelial integrity and barrier function. The aim of this study was to investigate the influence of atopy on airway epithelial integrity in asthma and to measure E-cadherin levels in exhaled breath condensate as an indicator epithelial damage. A total of 74 patients with asthma (35 atopic and 39 non-atopic) and 39 healthy children were enrolled in this case-control study. Sociodemographic characteristics and asthma severity parameters in the last three-month period were recorded and pulmonary function tests were performed. Blood samples were obtained to measure serum immunoglobulin E (IgE) levels and peripheral blood eosinophil count, and exhaled breath condensate (EBC) was obtained to measure E-cadherin.EBC E-cadherin levels were significantly lower in the asthmatics when compared to non-atopic controls (0.109 (0.076) versus 0.191 (0.184) ng mL(-1) respectively, p = 0.01). Atopic and non-atopic asthmatic groups had lower EBC E-cadherin levels compared to the control group. (0.112 (0.060) ng ml(-1), 0.106 (0.089) ng ml(-1) and 0.191 (0.184) ng ml(-1), p = 0.02 and p < 0.01 respectively). However, EBC E-cadherin levels were not different between atopic and non-atopic asthmatics. The results of our study support the role of E-cadherin in the pathogenesis of asthma. However, the absence of difference in E-cadherin levels between atopic and non-atopic asthmatics suggests that allergic sensitization is not the primary factor for development of epithelial barrier dysfunction in asthma.

Abstract. Epithelial barrier dysfunction is important in the pathogenesis of asthma and allergic responses, and is therefore a therapeutic target. The aim of the present study was to investigate the effects of dexamethasone, a classic therapeutic agent, an anti-tumor necrosis factor agent (etanercept), which is used to treat difficult cases of asthma, and an anti-vascular endothelial growth factor (VEGF) agent (bevacizumab), which is an angiogenesis inhibitor, on zonula occludens (ZO) proteins in an experimental asthma model. The experimental model of asthma was developed using intraperitoneal (IP) and inhaled administration of ovalbumin in 38 BALB/c mice, which were divided into four groups. The control group (n=6) did not receive any treatment, while the four remaining groups (n=8 per group) received an IP injection of saline, etanercept, bevacizumab or dexamethasone, respectively. Occludin, claudin and junctional adhesion molecule (JAM) were immunohistochemically stained in the left middle lobe samples using an indirect avidin-peroxidase method, after which the staining was semiquantified with H-scores. Statistically significant differences were observed in the occludin, claudin and JAM H-scores among the four groups (P<0.001). In the untreated asthma, etanercept, bevacizumab and dexamethasone groups, the median H-scores for occludin were 93, 177, 280 and 198, respectively, while the H-scores for claudin were 82, 193.5, 274 and 202.5, respectively, and the median H-scores for JAM were 130, 210, 288 and 210, respectively. Pairwise comparisons revealed that all three ZO protein H-scores were significantly lower in the saline group when compared with each treatment group. However, the H-scores of the ZO proteins were not significantly different between the etanercept and dexamethasone groups. Furthermore, the bevacizumab group exhibited higher H-scores for all the proteins compared with the dexamethasone group. Therefore, antagonism of VEGF with bevacizumab restores the epithelial barrier to a greater extent when compared with dexamethasone treatment. This result may be promising for the development of novel therapeutic agents. IntroductionEpithelial tissue, in addition to forming a physical barrier to external stimuli, plays a major role in the regulation of the adaptive immune response. The physical barrier function of the epithelium is attained via cell-cell interactions and via impermeable tight junctions (TJs) that are located subapically (1).Claudins, occludin and junctional adhesion molecules (JAMs) are major constituent proteins of TJs. The claudin family comprises 24 members, and determines the TJ charge selectivity and the location of the paracellular space (2). In addition, human fetal lung cells have been shown to use differential claudin expression to regulate TJ permeability (3). Occludin is an additional protein that is important in barrier formation and regulation (2). JAM-1, which is a member of the immunoglobulin superfamily, has been shown to interact with zonula occludens (ZO)-1, occludin and...

Besides maintaining a physical barrier with adherens junctional (AJ) and tight junctional proteins, airway epithelial cells have important roles in modulating the inflammatory processes of allergic asthma. E-cadherin and β-catenin are the key AJ proteins that are involved in airway remodeling. Various mediators such as transforming growth factor-β (TGF-β), epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet derived growth factor (PDGF), insulin-like growth factor (IGF), tumor necrosis factor-α (TNF-α) and angiogenic factors, such as vascular endothelial growth factor (VEGF), are released by the airway epithelium in allergic asthma. The signaling pathways activated by these growth factors trigger epithelial-mesenchymal transition (EMT), which contributes to fibrosis and subsequent downregulation of E-cadherin. The present study used a mouse asthma model to investigate the effects of anti-VEGF, anti-TNF and corticosteroid therapies on growth factor and E-cadherin/β-catenin expression. The study used 38 male BALB/c mice, divided into 5 groups. A chronic mouse asthma model was created by treating 4 of the groups with inhaled and intraperitoneal ovalbumin (n= 8 per group). Saline, anti-TNF-α (etanercept), anti-VEGF (bevacizumab) or a corticosteroid (dexamethasone) were applied to each group by intraperitoneal injection. No medication was administered to the control group (n=6). Immunohistochemistry for E-cadherin, β-catenin and growth factors was performed on lung tissues and protein expression levels assessed using H-scores. Statistically significant differences were observed in E-cadherin, β-catenin, EGF, FG, and PFGF (P<0.001 for all) as well as the IGF H-scores between the five groups (P<0.005). Only anti-VEGF treatment caused E-cadherin and β-catenin levels to increase to the level of non-asthmatic control groups (P>0.005). All treatment groups had reduced TGF-β, PDGF and FGF H-scores in comparison with the untreated asthma group (P=0.001). The EGF and IGF levels were not significantly different between the untreated asthmatic and non-asthmatic controls. The results suggested that anti-VEGF and TNF-α inhibition treatments are effective in decreasing growth factors, in a similar manner to conventional corticosteroid treatments. Anti-VEGF and TNF inhibition therapy may be an effective treatment for remodeling in asthma while offering an alternative therapeutic option to steroid protective agents. The data suggested that anti-VEGF treatment offered greater restoration of the epithelial barrier than both anti-TNF-α and corticosteroid treatment.

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Introduction: Cystic fibrosis (CF) is characterized with chronic inflammation with neutrophil and related cytokines in airway secretions. We aimed to measure the levels of neutrophil related inflammatory markers as nitric oxide, IL-8, IL-17, leukotriene B4 and neutrophil elastase as well as e-cadherin in exhaled breath condensate (EBC), and to determine their relation with clinical findings. Methods: We consecutively enrolled cystic fibrosis patients into our clinics between the age of six and eighteen years who could cooperate for exhaled breath condensate to this case-control study (n = 30). The age and sex matched control group (n = 26) was enrolled. Spirometry was performed during the stable period and EBC samples were obtained for measurement of the markers. Results: The mean age of the subjects enrolled was 12.1(4.2) years and 40% were positive for P.Aeruginosa in sputum. Subjects who had P.Aeruginosa in sputum cultures had significantly lower FEV1, FVC and FEF 25/75 values compared to the ones without P.Aeruginosa (p = 0.002, p = 0.002 and p = 0.005 respectively). EBC neutrophil elastase levels were significantly higher in the CF patients compared to non-CF controls (3.11 ± 4.71 versus 0.90 ± 2.68, p = 0.04). Nitric oxide, IL-17, IL-8, e-cadherin, neutrophil elastase or leukotriene B4 levels in EBC of CF patients were not related to P.Aeruginosa s infection, FEV1 levels or hospital admission in the last year. Conclusion: In our study, neutrophil elastase levels in EBC are higher in CF patients compared to non-CF controls. This is independent of acute infection and is evidence to the persistence of neutrophilic lung injury. However, EBC NO, IL-8, IL-17, e-cadherin, neutrophil elastase and leukotriene B4 levels as inflammatory markers, are not correlated with disease progression or clinical findings.