Background: Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airway obstruction. Smoking causes persistent inflammation in lung tissue. However, differences in inflammatory responses between the large and small airways have not been systematically explored among smokers with and without COPD. Objectives: The aim of our research was to characterise the expression and localisation of NF-ĸBp65 and histone deacetylase 2 (HDAC2) as well as inflammatory cell (macrophages, lymphocytes, neutrophils) distribution in large and small airways, in nonsmokers and in smokers with and without COPD. Methods: Nineteen nonsmokers, 20 smokers with normal lung ventilation function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate NF-ĸBp65 and HDAC2 expression and identify inflammatory cells in airways. Results: COPD patients had increased NF-ĸBp65 expression compared to nonsmokers and smokers without COPD, in both large and small airways, which corresponded to increased numbers of macrophages, CD8+ T lymphocytes and neutrophils. COPD patients had more macrophages in large compared to small airways and more CD8+ T lymphocytes and neutrophils in small compared to large airways. HDAC2 expression was significantly downregulated in smokers with COPD in small compared to large airways. Conclusions: Our findings indicate a nonuniform distribution of inflammatory cells throughout the bronchial tree. However, in both smokers with and without COPD, similar patterns of inflammatory processes occur in both large and small airways. The difference between smokers with and without COPD is only quantitative.

Metformin is prospective for treatment of diabetic nephropathy.

Anti-ischaemic drug mildronate suppresses fatty acid metabolism and increases glucose utilization in myocardium. It was proposed that it could produce a favourable effect on metabolic parameters and glucose transport in diabetic animals. Rats with streptozotocin diabetes mellitus were treated with mildronate (100 mg/kg daily, per os, 6 weeks). Therapeutic effect of mildronate was monitored by measuring animal weight, concentrations of blood glucose, insulin, blood triglycerides, free fatty acids, blood ketone bodies and cholesterol, glycated haemoglobin per cent (HbA1c%) and glucose tolerance. GLUT1 mRNA and protein expression in kidneys, heart, liver and muscles were studied by means of real time RT-PCR and immunohistochemistry correspondingly. In the streptozotocin + mildronate group, mildronate treatment caused a significant decrease in mean blood glucose, cholesterol, free fatty acid and HbA1c concentrations and improved glucose tolerance. Induction of streptozotocin diabetes mellitus provoked increase of both GLUT1 gene and protein expression in kidneys, heart and muscle, mildronate treatment produced normalization of the GLUT1 expression levels. In the liver a similar effect was observed for GLUT1 protein expression, while GLUT1 gene expression was increased by mildronate. Mildronate produces therapeutic effect in streptozotocin diabetes model. Mildronate normalizes the GLUT1 expression up-regulated by streptozotocin diabetes mellitus in kidneys, heart, muscle and liver. Copyright © 2011 John Wiley & Sons, Ltd.

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