Background: Resistin is an adipocytokine, associated with obesity and inflammation. Its exact role in insulin resistance and diabetes in the general population is still controversial. The relation between resistin plasma levels, insulin resistance and risk of impaired glucose metabolism in OSA patients has not been investigated. Materials and methods: Plasma levels of resistin were measured in 67 patients with OSA and impaired glucose metabolism. 34,7% (23/67) had diabetes; 40% (27/67) patients had impаired glucose tolerance(IGT); 25,3%(17/67) had normal glucose metabolism (NGM). The association between resistin, BMI, obesity, markers of insulin resistance, oxidative stress and sleep study characteristics was analysed. The different groups of patients were compared in regards to glucometabolic parameters and biomarkers of oxidative stress – isoprostanes and insulin resistance – free fatty acids (FFA). Results: Plasma levels of resistin were higher in patients with diabetes (6,12 ±5,93ng/ml), compared to those with IGT (3,85±2,81ng/ml, p-0,021) and NGM (3,77±3,23, p-0,043). Resistin did not differ between patients with IGT and NGM (p-0,954). In OSA patients with BMI>40 resistin plasma levels correlated neither to the clinical parameters (BMI, IRI, HOMA-I, HbA1C, AHI, desaturation index), nor to the biomarkers of oxidative stress and insulin resistance. Free fatty acids (0,232>0,177mmol/l, p-0,037) were higher in diabetics in comparison to NGM. Conclusions: Plasma resistin levels in OSA patients with BMI>40 are independent of insulin resistance and are not associated with the parameters, characterising the oxidative stress or severity of OSA. Resistin could be used in a multiple panel of clinical and biomarkers to discern patients with diabetes from those with IGT; in OSA patients with BMI >40 resistin together with HbA1C could discern patients with diabetes from those with NGM. In OSA patients with BMI >40 FFA and HbA1C are useful clinical markers in assessing the risk of dysglycaemia among patients with normal and IGT.

Peer reviewed article authored by (Cherneva RV, Georgiev OB, Petrova DS, Trifonova NL, Stamenova M, Ivanova V, Vlasov VI). Read article or submit your manuscript for publishing.

Objective: Alpha-B-crystallin, a small heat-shock protein, recently gained major interest because of its differential expression during tumourigenesis and metastasis in various epithelial tumours. The purpose of this study was to investigate the expression of alpha-B-crystallin and its biologic and prognostic significance in non-small-cell lung cancer (NSCLC). Methods: Immunohistochemical analysis was performed on a tissue microarray slide containing samples from 146 NSCLC patients who were operated on between 2004 and 2005. Results: Cytoplasmic and nuclear staining was detected. Squamous cell carcinomas and adenocarcinomas had a distinctive profile of expression. The cytoplasmic staining of the tumours, however, is related to the local invasion – T-factor (p = 0.044). Nuclear staining was more commonly detected in advanced stages, and was a biomarker of an aggressive tumour biology (p = 0.042). Kaplan–Meier analysis showed that patients with positive nuclear staining had shorter overall survival (log-rank p = 0.002). Using Cox’s proportional hazards model, we performed multivariate analyses to assess the independent prognostic value of nuclear staining. The variables used included age, histology, gender and stage. Alpha-B-crystallin was an independent negative prognostic factor of survival in addition to clinical stage. Conclusions: Alpha-B-crystallin plays an essential role in NSCLC biology and its nuclear staining is an independent factor of poor survival. Its clinical application in molecular biologic substaging of NSCLC patients needs further validation.

Background: The presence of abnormal heart rate recovery (HRR) and chronotropic incompetence (CI) suggests autonomic dysfunction (AD) and is associated with diminished physical activity and increased cardio-vascular (CV) risk. Aim: Our aim is to analyse the correlation between AD and airflow obstruction - forced expiratory volume in 1 s (FEV1), dynamic hyperinflation (DH) and disease prognosis - the BODE – index (BMI; Obstruction – FEV1;Dyspnea – mMRC;E – exercise capacity) in non-severe COPD patients without overt CV comorbidities. Methods: We used cardio-pulmonary exercise testing (CPET) with 67 subjects. Inspiratory capacity (IC) manouevres were performed for DH assessment. Echocardiography was executed before CPET and 1−2 min after peak exercise. Stress left ventricular diastolic dysfunction (LVDD) was assumed if stress E/e’ > 15.Wilkoff method calculated the metabolic-chronotropic relationship (MCR). Chronotropic incompetence (CI) and abnormal HR recovery (HRR) were determined. Main results: CI was detected in 44% of the mild and 65% of the moderate COPD patients. Abnormal HRR was present in 75% of the mild and 78% of the moderate COPD subjects. Multivariate regression analysis showed no association between FEV1, CPET parameters, BODE index, stress LVDD and AD. DH was the only independent predictor for both abnormal HRR and CI. Conclusion: Evaluation of AD during incremental CPET unravels lung hyperinflation as a potential mechanism of attenuated HR response and diminished physical activity in non-severe COPD free of overt CV comorbidities. This multifaceted approach to dyspnea may facilitate the discrimination of its pathogenesis and improve its proper clinical management.

Oxidative stress generated by cigarette smoking, environmental pollution, or other noxious particles leads to epigenetic changes in the cells of the respiratory tract. They reflect cell adaptation in response to chronic exposure to external factors. Although there is no change in the genetic code, epigenetic changes may be heritable and translated from one generation to another, accumulating abnormalities and rendering cells into entirely different phenotype, causing disease. DNA methylation, post-translation histone modification, ubiquitination, sumoylation and miRNA transcriptional regulation are the major processes that are responsible for the epigenetic control of gene expression. All of them are reversible. They can be regulated by targeting specific enzymes/proteins involved in the process in order to mitigate inflammation. Chronic respiratory diseases have epigenetic signatures that affect gene expression in the lung. Targeting them provides the development of novel diagnostic and therapeutic approaches in respiratory medicine. Nutrigenomics reveals the beneficial effect of natural phytochemicals, affecting key steps in the signaling pathways of chronic respiratory diseases.