Downregulation of lung mitochondrial prohibitin in COPD

Summary Prohibitins (PHB1 and PHB2) are versatile proteins located at the inner mitochondrial membrane, maintaining normal mitochondrial function and morphology. They interact with the NADH dehydrogenase protein complex, which is essential for oxidoreductase activity within cells. However, their expression in lung epithelium, especially in smokers and patients with inflammatory lung diseases associated with increased oxidative stress, such as COPD, is unknown. Lung tissue specimens from 45 male subjects were studied: 20 COPD patients [age: 65.7 AE 5.8 years, smoking: 84.6 AE 33.6 pack-years, FEV 1 (%pred.): 58.7 AE 14.6, FEV 1 /FVC (%): 63.8 AE 9.4], 15 non-COPD smokers [age: 59.0 AE 12.1 years, smoking: 52.5 AE 20.8 pack-years, FEV 1 (%pred.): 85.5 AE 14.2, FEV 1 /FVC (%): 78.5 AE 4.7] and 10 non-smokers. Quantitative real-time PCR experiments were carried out for PHB1 and PHB2, using b-actin as internal control. Non-COPD smokers exhibited lower PHB1 mRNA levels when compared to non-smokers (0.55 AE 0.06 vs. 0.90 AE 0.06, P Z 0.043), while PHB1 expression was even further decreased in COPD patients (0.32 AE 0.02), a statistically significant finding vs. both non-COPD smokers (P Z 0.040) and non-smokers (P < 0.001). By contrast, PHB2 levels were similar among the three study groups. Western blot analysis for the PHB1 protein verified the qPCR results (non-smokers: 1.77 AE 0.13; non-COPD smokers: 0.97 AE 0.08; COPD patients: 0.59 AE 0.10, P Z 0.007). Further analysis revealed that PHB1 downregulation in COPD patients cannot be attributed solely to smoking, and that PHB1 expression levels are associated with the degree of airway obstruction [FEV 1 (P mRNA Z 0.004, P protein Z 0.014)]. The significant downregulation of PHB1 in COPD and non-COPD smokers in comparison to non-smokers possibly reflects a distorted mitochondrial function due to decreased mitochondrial stability, especially in the mitochondria of COPD patients.

Increased apoptosis of neutrophils in induced sputum of COPD patients

SummaryAimThe aim of the current study was to evaluate apoptosis in induced sputum neutrophils and to investigate the relationship between the number of apoptotic cells and clinical parameters in COPD patients.MethodsTwenty-four COPD ex-smoker patients and 10 healthy controls were included in the study. All subjects underwent clinical evaluation and sputum induction. Sputum cell in situ apoptosis was identified using white light microscopy and TUNEL assay technique. Apoptosis of neutrophils obtained by sputum induction was expressed as apoptotic rate (AR=percentage of apoptotic neutrophils over the number of neutrophils measured).ResultsTUNEL assay revealed statistically significant higher AR in COPD patients than controls (p=0.004). Patients with FEV1<50%pred had significantly higher median (IQR) AR (%) compared to patients with FEV1≥50% [26.3 (16–29) vs 13.1 (8.6–21), p=0.01]. No significant association was found between the number of apoptotic cells and age, symptoms or medication used.ConclusionThe significantly increased apoptotic rate of neutrophils that were found in COPD patients with advanced disease compared to controls might reflect either a deregulation of apoptosis of neutrophils or, a reduced clearance of apoptotic neutrophils from the airways. The pathophysiologic significance of the observed phenomenon has to be further explored

Effects of antifibrotic agents on TGF-β1, CTGF and IFN-γ expression in patients with idiopathic pulmonary fibrosis

SummaryIdiopathic pulmonary fibrosis (IPF) is a deadly disease, largely unresponsive to treatment with corticosteroids and immunosuppressives. The aim of this randomized, prospective, open-label study was to characterize the molecular effects of IFN-γ-1b and colchicine, on biomarkers expression associated with fibrosis (TGF-β, CTGF) and immunomodulatory/antimicrobial activity (IFN-γ), in the lungs of patients with IPF.Fourteen (14) patients with an established diagnosis of IPF received either 200μg of IFN-γ-1b subcutaneously three times per week, or 1mg of oral colchicine per day, for 24 months. Using RT-PCR assay, we evaluated the transcription levels of transforming growth factor β1 (TGF-β1), connective-tissue growth factor (CTGF), and interferon-γ (IFN-γ) genes in lung tissue before and after treatment with IFN-γ-1b or colchicine.Marked mRNA expression of TGF-β1 and CTGF, but complete lack of interferon-γ was detected in fibrotic lung tissue at entry. After treatment, both groups exhibited increased expression of IFN-γ gene at 6 months that was sustained at 24 months. The expression of CTGF and TGF-β1 remained almost stable before and after treatment, in the IFN-γ-1b group, while TGF-β1 was statistically decreased after therapy, in the colchicine group (p=0.0002). Significant difference in DLCO (% pred), was found between the two treatment groups in favor of IFN-γ-1b group (p=0.04). In addition, the IFN-γ-1b group showed stability in arterial PO2 while the colchicine group significantly deteriorated (p=0.02).In conclusion, we report the effect of antifibrotic agents (IFN-γ-1b and colchicine) in TGF-β, CTGF, and endogenous IFN-γ gene expression, in human fibrosis. However, extended studies are needed to verify the pathophysiological consequences of these findings

Severe airway stenosis associated with Crohn's disease: Case report

BACKGROUND: Symptomatic respiratory tract involvement is not common in Crohn's disease. Upper-airway obstruction has been reported before in Crohn's disease and usually responds well to steroid treatment. CASE PRESENTATION: We report a case of a 32-year old patient with Crohn's disease who presented with progressively worsening dyspnea on exertion. Magnetic Resonance Imaging of the chest and bronchoscopy revealed severe tracheal stenosis and marked inflammation of tracheal mucosa. Histopathology of the lesion showed acute and chronic inflammation and extended ulceration of bronchial mucosa, without granulomas. Tracheal stenosis was attributed to Crohn's disease after exclusion of other possible causes and oral and inhaled steroids were administered. Despite steroid treatment, tracheal stenosis persisted and only mild symptomatic improvement was noted after 8 months of therapy. The patient subsequently underwent rigid bronchoscopy with successful dilatation and ablation of the stenosed areas and remission of her symptoms. CONCLUSION: Respiratory involvement in Crohn's disease might be more common than appreciated. Interventional pulmonology techniques should be considered in cases of tracheal stenosis due to Crohn's disease refractory to steroid treatment

Identifying Privacy Related Requirements for the Design of Self-Adaptive Privacy Protections Schemes in Social Networks

Social Networks (SNs) bring new types of privacy risks threats for users; which developers should be aware of when designing respective services. Aiming at safeguarding users’ privacy more effectively within SNs, self-adaptive privacy preserving schemes have been developed, considered the importance of users’ social and technological context and specific privacy criteria that should be satisfied. However, under the current self-adaptive privacy approaches, the examination of users’ social landscape interrelated with their privacy perceptions and practices, is not thoroughly considered, especially as far as users’ social attributes concern. This study, aimed at elaborating this examination in depth, in order as to identify the users’ social characteristics and privacy perceptions that can affect self-adaptive privacy design, as well as to indicate self-adaptive privacy related requirements that should be satisfied for users’ protection in SNs. The study was based on an interdisciplinary research instrument, adopting constructs and metrics from both sociological and privacy literature. The results of the survey lead to a pilot taxonomic analysis for self-adaptive privacy within SNs and to the proposal of specific privacy related requirements that should be considered for this domain. For further establishing of our interdisciplinary approach, a case study scenario was formulated, which underlines the importance of the identified self-adaptive privacy related requirements. In this regard, the study provides further insight for the development of the behavioral models that will enhance the optimal design of self-adaptive privacy preserving schemes in SNs, as well as designers to support the principle of PbD from a technical perspective

DNA Damage Due to Oxidative Stress in Chronic Obstructive Pulmonary Disease (COPD)

Society (ERS) Statement, chronic obstructive pulmonary disease (COPD) is defined as a preventable and treatable disease with a strong genetic component, characterized by airflow limitation that is not fully reversible, but is usually progressive and associated with an enhanced inflammatory response of the lung to noxious particles or gases. The main features of COPD are chronic inflammation of the airways and progressive destruction of lung parenchyma and alveolar structure. The pathogenesis of COPD is complex due to the interactions of several mechanisms, such as inflammation, proteolytic/antiproteolytic imbalance, oxidative stress, DNA damage, apoptosis, enhanced senescence of the structural cells and defective repair processes. This review focuses on the effects of oxidative DNA damage and the consequent immune responses in COPD. In susceptible individuals, cigarette smoke injures the airway epithelium generating the release of endogenous intracellular molecules or danger-associated molecular patterns from stressed or dying cells. These signals are captured by antigen presenting cells and are transferred to the lymphoi