Detection of reactive oxygen metabolites in malignant and adjacent normal tissues of patients with lung cancer

BACKGROUND: Different types of reactive oxygen metabolites (ROMs) are known to be involved in carcinogenesis. Several studies have emphasized the formation of ROMs in ischemic tissues and in cases of inflammation. The increased amounts of ROMs in tumor tissues can either be because of their causative effects or because they are produced by the tumor itself. Our study aimed to investigate and compare the levels of ROMs in tumor tissue and adjacent lung parenchyma obtained from patients with lung cancer. METHODS: Fifteen patients (all male, mean age 63.6 ± 9 years) with non-small cell lung cancer were enrolled in the study. All patients were smokers. Of the patients with lung cancer, twelve had epidermoid carcinoma and three had adenocarcinoma. During anatomical resection of the lung, tumor tissue and macroscopically adjacent healthy lung parenchyma (control) that was 5 cm away from the tumor were obtained. The tissues were freshly frozen and stored at −20°C. The generation of ROMs was monitored using luminol- and lucigenin-enhanced chemiluminescence (CL) techniques. RESULTS: Both luminol (specific for (.)OH, H(2)O(2), and HOCl(-)) and lucigenin (selective for O(2)(.-)) CL measurements were significantly higher in tumor tissues than in control tissues (P <0.001). Luminol and lucigenin CL measurements were 1.93 ± 0.71 and 2.5 ± 0.84 times brighter, respectively, in tumor tissues than in the adjacent parenchyma (P = 0.07). CONCLUSION: In patients with lung cancer, all ROM levels were increased in tumor tissues when compared with the adjacent lung tissue. Because the increase in lucigenin concentration, which is due to tissue ischemia, is higher than the increase in luminol, which is directly related to the presence and severity of inflammation, ischemia may be more important than inflammation for tumor development in patients with lung cancer

Lipid Peroxidation and Paraoxonase Activity in Nocturnal Cyclic and Sustained Intermittent Hypoxia

Purpose Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) have been known to be associated with atherosclerosis and hypoxia which was suggested to have an important role in this process by the way of increased oxidative stress. In the present study, we aimed to evaluate the effects of nocturnal hypoxia pattern (intermittent versus sustained) on serum lipid peroxidation and paraoxonase (PON) activity. Methods Blood collections were performed in 44 OSA, 11 non-apneic, nocturnal desaturated COPD, and 14 simple snorer patients after full-night polysomnographic recordings. Nocturnal sleep and respiratory parameters, oxygen desaturation indexes, serum malondialdehyde (MDA) levels by measuring with the help of the formation of thiobarbituric acid reactive substances (TBARS), and PON activity were assessed in all subjects. Results OSA and COPD patients showed nocturnal hypoxemia, with a minimum oxygen saturation (SaO2) in ranges of 53–92 % and 50–87 %, respectively. The mean levels of TBARS was 15.7±3.6 nmol and 15.3±3.4 nmol malondialdehyde (MDA)/ml in OSA and COPD patients, respectively, while the mean level of the control group was 4.1±1.2 nmol MDA/ml. The mean PON activity was found to be 124.2± 35.5 U/l in OSA patients and 124.6±28.4 U/l in COPD patients. The mean PON activity of the control group was 269.0±135.8 U/l. The increase in TBARS levels and the decrease in PON1 levels were statistically significant in both OSA and COPD patients according to controls (p<0.001 for TBARS as well as PON1). Conclusion The results of this study revealed that both OSA and non-apneic, nocturnal desaturated COPD patients showed increased levels of lipid peroxidation and decreased PON activity despite the differences in nocturnal hypoxia pattern

Matrix Metalloproteinase-9 Level and Gene Polymorphism in Sleep Disordered Breathing Patients with or without Cardiovascular Disorders

Objective: Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular morbidity and mortality. We aimed to investigate the matrix metalloproteinase-9 (MMP-9) level and MMP-9 gene polymorphism in sleep apnea patients with or without cardiovascular disease. Study Design: Case-control study. Material and Methods: Two hundred nine patients [Mean age (±SD), 47 (±12) yrs; M/F, 170/39] diagnosed with sleep-disordered breathing were included in the study. Serum MMP-9 level was performed using enzyme-linked immunosorbant assay (ELISA) and MMP-9 gene polymorphism with polymerase chain reaction-restriction fragment length polymorphism. We divided the patient group into two subgroups: (1) patients with confirmed cardiovascular disease, i.e. CV-P Group and (2) patients without cardiovascular disease, CV-N Group. We compared all parameters between the two groups. Results: There were 56 OSAS patients with cardiovascular disorder (CV-positive group) and 153 OSAS patients without cardiovascular disorder (CVnegative group). CC, CT and TT genotype distributions between groups were similar [31 (55%), 25 (45%), 0 (0%) vs 88 (57%), 61 (40%), 4 (3%); respectively, p>0.05]. MMP-9 level was significantly higher in CV-P patients (442.7±139.3 pg/mL) than in CV-N patients (364.4±165.0 pg/mL; p=0.0018). Conclusion: Our results showed that the presence of MMP-9 polymorphism was not associated with cardiovascular disease. MMP-9 level was higher in OSAS patients with cardiovascular disorders than without cardiovascular disorders. Finally, MMP-9 genotype was not associated with serum MMP-9 levels

Pure Obstructive Sleep Apnea Syndrome and Erectile Dysfunction

Objective: The aim of this study is to investigate the existence of erectile dysfunction in patients with obstructive sleep apnea syndrome (OSAS) in which the other possible causes of erectile dysfunction were eliminated.Material and Methods: The study group consisted of 24 patients diagnosed as OSAS with polysomnographic evaluation, and 15 non-apneic controls (mean age; 41.0±8.8 and 42.3±7.9 year respectively) whose comorbidities which might be associated with erectile dysfunction were excluded. Daytime sleepiness was evaluated by Epworth Sleepiness Scale (ESS) and measurement of erectile function was performed by International Index of Erectile Function.Results: The rate of erectile dysfunction in OSAS and control groups were 54.2% and 33.3% respectively (p=0.204). The difference between mean erectile function scores of patient and control groups was non-significant (26.1±4.5 and 26.3±4.3 respectively, p=0.900). There was no correlation between erectile function scores and apnea hypnoea index (r=-0.140; p=0.395).Conclusion: Findings obtained from this study suggest that the high incidence of erectile dysfunction reported in OSAS patients seems to be related with concomitant comorbidities such as diabetes, atherosclerosis and neuroendocrine disorders rather than sleep apnea

Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome

OBJECTIVE: Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide. METHODS: The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples. RESULTS: Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05). CONCLUSION: Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels