Protection of Azidothymidine-Induced Cardiopathology in Mice by Mildronate, a Mitochondria-Targeted Drug

Azidothymidine, a nucleoside-analogue reverse transcriptase inhibitor (NRTI), is a commonly used antiretroviral drug in AIDS treatment, however its use is limited by severe toxic side effects due to its influence on mitochondria that result in myopathy, particularly affecting the cardiac muscle. We suggest that effective protection of azidothymidine- induced cardiopathology can be expected from drugs that are capable of targeting mitochondria. Therefore the present study in mice was carried out with mildronate, a cardioprotective drug of the aza-butyrobetaine class, which previously has been shown to act as a highly potent protector of mitochondrial processes. In our study, saline (control)…

A simple method of bronchoprovocation using a valved holding chamber.

This study was undertaken to ascertain whether the use of a valved holding chamber (VHC) during bronchial provocation testing might increase lung deposition and repeatability of the test relative to the tidal breathing method. The 2-min tidal breathing results were compared to five inhalations from a VHC device in patients using the Pari-provoII nebulizer (MMD = 2.1mkm). Lung and mouth deposition, losses though the exhaled air and losses before aerosol delivery to the patient's mouth were measured in patients using a radiolabeled 99Tc-DTPA solution and gamma camera. The study revealed that lung deposition was 67% with the VHC method, and losses with exhaled air were 29% of the inhaled amoun…

Increased sirtuin expression in patient with lung squamous cell carcinoma co-morbid with COPD

Background: COPD is frequently associated with comorbidities, the most serious and prevalent include lung cancer. Sirtuin 1 (SIRT1) is known to deacetylate histones and non-histone proteins including transcription factors thereby regulating metabolism, stress resistance, cellular survival, cellular senescence/aging. The aim of our study was to evaluate SIRT-1 expression in patients with lung squamous cell carcinoma and adenocarcinoma and these co-morbid with COPD. Methods: 93 patients with lung nonsmall cell lung carcinoma co-morbid with moderate severity COPD (n=29) or without COPD were enrolled in the study. Lung function testing was performed within one week before lung surgery. SIRT-1 e…

Detection of lung cancer in exhaled breath with an electronic nose using support vector machine analysis

Lung cancer is one of the most common malignancies and has a low 5-year survival rate. There are no cheap, simple and widely available screening methods for the early diagnostics of lung cancer. The aim of this study was to determine whether analysis of exhaled breath with an artificial olfactory sensor using support vector analysis can differentiate patients with lung cancer from healthy individuals and patients with other lung diseases, regardless of the stage of lung cancer and the most common comorbidities. Patients with histologically or cytologically verified lung cancer, healthy volunteers and patients with other lung diseases (e.g. chronic obstructive pulmonary disease (COPD), asthm…

P-147PLASMA PLATELET FACTOR 4 AS PREDICTOR OF ANGIOGENIC ACTIVITY: DIAGNOSTIC AND PROGNOSTIC TOOL FOR EARLY STAGE NON-SMALL CELL LUNG CANCER

Effects of the prolonged thoracic epidural analgesia on ventilation function and complication rate after the lung cancer surgery.

Thoracic epidural analgesia has been considered to have a good anesthetic efficacy and to decrease the postoperative complication rate, while its effect upon the ventilation function is still the topic of many clinical studies. The aim of this study was to evaluate the course of early postoperative period using thoracic epidural analgesia. Material and methods. A total of 453 patients undergoing the operation due to the non–small cell carcinoma were selected and examined. Their postoperative complications and mortality rate were evaluated. In 79 patients, arterial oxygen saturation (SaO2), forced vital capacity, forced expiratory volume in the first second, and the efficacy of analgesia wer…

Association between nasal and bronchial resistance in patients with COPD

Background: During the past decade, various studies have documented the presence of sinonasal inflammation in lower airways diseases. The influence of airways inflammation on nasal airways patency was demonstrated in asthmatic patients; however, such association was not confirmed in patients with COPD. Purpose: The aim of the study was to compare the relationship between nasal resistance and lower airways patency in COPD patients and healthy controls. Material and Methods: 4-Phase-Rhinomanometry and spirometry were performed on COPD patients (n=26) and in the corresponding age control group (n=15). To compare the effective nasal resistance in inspiration, expiration and total breathing (Ref…

Regional Lung Blood Perfusion Measured With Laser Doppler Method During Body Position Change, Valsalva Manoeuvre and Cardiopulmonary Bypass

Regional Lung Blood Perfusion Measured With Laser Doppler Method During Body Position Change, Valsalva Manoeuvre and Cardiopulmonary Bypass Methodological approaches to investigate local regulatory mechanisms of lung blood supply in humans are restricted. We tried a new approach using laser Doppler technique. During bronchoscopy, an angled laser Doppler flow probe was introduced through a biopsy channel and wedged into small bronchus. Laser light penetrated the wall of small bronchus and was reflected from blood cells running through neighbouring capillaries. Regional blood perfusion changes were recorded during body position change from vertical to supine and back to vertical, while perfor…

H1-antihistamines suppress wheal-and-flare reaction and skin blood perfusion measured by Laser Dopppler flowmetry: randomized, double-blind, placebo-controlled, crossover design study

H1-antihistamines suppress wheal-and-flare reaction and skin blood perfusion measured by Laser Dopppler flowmetry: randomized, double-blind, placebo-controlled, crossover design study The aim of our study was to compare the influence of pre-treatment with H1-antihistamines (levocetirizine, desloratadine, clemastine, quifenadine, and sequifenadine) and a placebo on the histamine-induced weal and flare reaction, increase of skin blood perfusion and sedation. Thirty healthy volunteers were enrolled in the study. The study design was a prospective, randomised, double-blind, placebo-controlled, crossover, balanced clinical trial. Volunteers in randomised and double-blind order were treated with …

Splanchnic perfusion and regional pulmonary blood flow during cardiac bypass

Detection of lung cancer with electronic nose and logistic regression analysis.

Lung cancer is a very common malignancy with a low five-year survival rate. Artificial olfactory sensor (electronic nose) is a tool that recently has been studied as a probable optimal screening tool for early detection of lung cancer, but still no statistical method has been put forward as the preferable one. The aim of the study was to explore the use of logistic regression analysis (LRA) to analyse patients' exhaled breath samples with electronic nose in order to differentiate lung cancer patients (regardless of the stage of the cancer) from patients with other lung diseases and healthy individuals. Patients with histologically or cytologically verified, untreated lung cancer, patients w…

Increased innate and adaptive immune responses in induced sputum of young smokers

Background and objectives: It is known that chronic obstructive pulmonary disease (COPD) development process is imperceptible and can be asymptomatic for 20 or more years. It is of great importance to diagnose early inflammatory changes that can lead to COPD in young asymptomatic cigarette smokers. The aim of our study was to analyze the cell spectrum of induced sputum (IS) of young cigarette smokers, with emphasis on T-regulatory cells. Materials and methods: A total of 20 healthy nonallergic smokers, 20 nonsmokers and 20 COPD patients were enrolled in the study. After lung function measurements were taken, we performed sputum induction and analyzed sputum cells. We evaluated the cell coun…

Breath testing as a method for detecting lung cancer

Early diagnosis of lung cancer is important due to high mortality in late stages of the disease. An ideal approach for population screening could be the breath analysis, due to its non-invasiveness, simplicity and cheapness. Using sensitive methods of analysis like gas chromatography/mass spectrometry in exhaled air of cancer patients were discovered some volatile organic compounds - possible candidates for cancer markers. However, these compounds were not specific for cancer cells. At the same time, integrative approaches used to analyze the exhaled breath have demonstrated high sensitivity and specificity of this method for lung cancer diagnosis. Such integrative approaches include detect…

Patterns of Inflammatory Responses in Large and Small Airways in Smokers with and without Chronic Obstructive Pulmonary Disease

<i>Background:</i> 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. <i>Objectives:</i> 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. <i>Methods:</i&gt…

Distinct influence of atypical 1,4-dihydropyridine compounds in azidothymidine-induced neuro- and cardiotoxicity in mice ex vivo.

This study demonstrates the effective protection by compounds of atypical 1,4-dihydropyridine (DHP) series cerebrocrast, glutapyrone and tauropyrone against neuro- and cardiotoxicity caused by the model compound azidothymidine, a well-known mitochondria-compromising anti-HIV drug. In previous in vitro experiments, we have demonstrated distinct effects of these DHP compounds to influence mitochondrial functioning. In the present in vivo experiments, DHP compounds were administered intraperitoneally in mice daily for 2 weeks, per se and in combinations with azidothymidine at doses: azidothymidine 50 mg/kg; cerebrocrast 0.1 mg/kg; glutapyrone 1 mg/kg; and tauropyrone 1 mg/kg. At the end of the…

Long-term survival after lobectomy and pneumonectomy in patients with stage II non-small cell lung cancer (NSCLC)

Decreased FOXP3 expression in small airways of smokers with COPD

CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients. A total of 19 nonsmokers, 20 smokers with normal lung function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral nonsmall cell carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate FOXP3 expression in large a…

Different Patterns of Lung Sirtuin Expression in Smokers With and Without Chronic Obstructive Pulmonary Disease

Background and Objective. Chronic obstructive pulmonary disease is characterized by persistent and modified inflammatory responses in lung. Human sirtuin, an antiaging and antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins. The aim of our study was to compare the expression of sirtuin in large and small airways in nonsmokers, asymptomatic smokers, and smokers with chronic obstructive pulmonary disease. Material and Methods. A total of 12 nonsmokers, 14 asymptomatic smokers, and 12 smokers with moderate chronic obstructive pulmonary disease were enrolled into the study…