Showing papers by "Meral Yüksel published in 2013"

Lipid peroxidation and paraoxonase activity in nocturnal cyclic and sustained intermittent hypoxia

Abstract: 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.

Protein kinase C activation causes neurite retraction via cyclinD1 and p60-katanin increase in rat hippocampal neurons.

Abstract: Neurons are differentiated postmitotic cells residing in G0 phase of the cell cycle and are unable to proceed through G1 phase, in which cyclinD1 needs to be up-regulated for initiation. Yet, a growing body of evidence has shown that cell cycle re-activation via cyclinD1 up-regulation drives neurons into apoptosis. By contrast, there is also evidence demonstrating cell cycle proteins playing roles in neuronal differentiation. cyclinD1 has been shown to be differently regulated by protein kinase C alpha (PKC-α) in various mitotic cells. Based on these different effects, we investigated the role of PKC-α on cyclinD1 regulation in hippocampal neurons. Neurons were treated with PKC activator, PMA, and analysed for subcellular distributions of PKC-α and cyclinD1. Remarkably, PMA treatment increased nuclear PKC-α and cyclinD1, but not PKC-e in hippocampal neurons. Increases in nuclear PKC-α and cyclinD1 were accompanied by microtubule re-organisation via increases in tau and retinoblastoma protein phosphorylation levels. Increased p60-katanin and p53 changed the neuronal morphology into neurons with shorter, but increased number of side branches. Since up-regulation of cell cycle is associated with apoptosis in neurons, we also analysed changes in Bax, Bcl-2 early and PARP (poly(ADP-ribose)polymerase), caspase3 late apoptotic markers. However, we did not observe any indication of apoptosis. These data suggest that in addition to their previously known roles in mitotic cells on cell cycle regulation, PKC-α and cyclinD1 seem to be important for differentiation, and nuclear PKC-α and cyclinD1 interfere with differentiation by promoting microtubule re-organisation through PKC signaling without triggering apoptosis.

A study comparing the efficacy of antimicrobial agents versus enzyme (P-gp) inducers in the treatment of 2,4,6 trinitrobenzenesulfonic acid-induced colitis in rats.

Abstract: The intestinal microflora is an important cofactor in the pathogenesis of intestinal inflammation; and the epithelial cell barrier function is critical in providing protection against the stimulation of mucosal immune system by the microflora. In the present study, therapeutic role of the antibacterial drugs rifampicin and ciprofloxacine were investigated in comparison to spironolactone, an enzyme inducer, in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis of the rats. Drugs were administered for 14 days following induction of colitis. All drug treatments ameliorated the clinical hallmarks of colitis as determined by body weight loss and assessment of diarrhea, colon length, and histology. Oxidative damage and neutrophil infiltration as well as nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α) expressions that were increased during colitis, were decreased significantly. Rifampicin and ciprofloxacin were probably effective due to their antibacterial and immunomodulating properties. The multidrug resistence gene (MDR1) and its product p-glycoprotein (P-gp) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). In the present study, findings of the P-gp expression were inconclusive but regarding previous studies, it can be suggested that the beneficial effects of rifampicin and spironolactone may be partly due to their action as a P-gp ligand. Spironolactone has been reported to supress the transcription of proinflamatory cytokines that are considered to be of importance in immunoinflammatory diseases. It is also a powerful pregnane X receptor (PXR) inducer; thus, inhibition of the expression of NF-κB and TNF-α, and amelioration of inflammation by spironolactone suggest that this may have been through the activation of PXR. However, our findings regarding PXR expression were inconclusive. Activation of PXR by spironolactone probably also contributed to the induction of P-gp, resulting in extrusion of noxious substances from the tissue.

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

Abstract: 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 (aplusmn;SD), 47 (aplusmn;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, pagt;0.05]. MMP-9 level was significantly higher in CV-P patients (442.7aplusmn;139.3 pg/mL) than in CV-N patients (364.4aplusmn;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. Turkish Baslik: Kardiyovaskuler Hastaligi olan ve olmayan Obstruktif Uyku Apne Sendromlu Hastalarda Matriks Metalloproteinaz-9 Aktivitesi ile Gen Polimorfizmi Anahtar Kelimeler: Kardiyovaskuler hastaliklari, MMP-9, polimorfizm, uyku apnesi, hipertansiyon Amac: Obstruktif uyku apne sendromu (OUAS) artmis kardiyovaskuler morbidite ve mortalite ile iliskilidir. Bu calismada kardiyovaskuler hastaligi olan ve olmayan uyku apneli hastalarda matriks metalloproteinaz-9 (MMP-9) duzeyi ile MMP-9 gen polimorfizminin arastirilmasi amaclandi. Gerec ve Yontemler: Uykuda solunum bozuklugu teshisi almis 209 hasta [Ortalama yas (aplusmn;SS), 47 (aplusmn;12) yil; E/K, 170/39] calismaya dahil edildi. Serum MMP-9 duzeyi ELISA, MMP-9 gen polimorfizmi polimeraz zincir reaksiyonu ve restriksiyon fragmani uzunluk polimorfizmi ile DNA orneklerinde belirlendi. Hastalar kardiyovaskuler hastaligi olan, KV-P grubu ve kardiyovaskuler hastaligi olmayan, KV-N grubu olmak uzere iki alt gruba ayrildi. Bulgular: Kardiyovaskuler hastaligi olan (KV-P grup) 56 ve kardiyovaskuler hastaligi olmayan (KV-N grup) 153 OUAS hasta tesbit edildi. Gruplar arasi CC, CT ve TT genotip dagilimi benzer [31 (55%), 25 (45%), 0 (0%) vs 88 (57%), 61 (40%), 4 (3%); sirasiyla, pagt;0.05] tesbit edildi. MMP-9 duzeyi KV-P hastalarda (442.7aplusmn;139.3 pg/mL) KV-N hastalara (364.4aplusmn;165.0 pg/mL) gore anlamli (p=0.0018) yuksek saptandi. Sonuc: Bulgularimiz, MMP-9 polimorfizm varliginin kardiyovaskuler hastaliklarla iliskili olmadigini gosterdi. MMP-9 duzeyi kardiyovaskuler hastaligi olan OUAS'li hastalarda kardiyovaskuler hastaligi olmayanlara gore yuksek saptandi. Sonuc olarak, MMP-9 genotipi serum MMP-9 duzeyi ile iliskili bulunmadi.

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

Abstract: 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. 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. Both luminol (specific for .OH, H2O2, and HOCl-) and lucigenin (selective for O2.-) 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). 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.

The effect of betulinic acid on TNBS-induced experimental colitis

Abstract: In this study we have investigated the possible protective effect of betulinic acid (BA) on colonic inflammation in rats. Colitis was induced in Sprague-Dawley rats of both sexes by intracolonic administration of 1 ml trinitrobenzene sulphonic acid (TNBS). Colitisinduced rats received orogastrically either betulinic acid (50 mg/kg/day) or vehicle (0.05% DMSO) for 3 days. At the 72nd hour of colitis induction, the rats were decapitated and trunk blood was collected for the measurement of TNF-, IL-1, lactate dehydrogenase (LDH) levels and total antioxidant capacity (AOC). The distal 8 cm of colon were scored macroscopically, and the degree of oxidant damage was evaluated by malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase activity (MPO), collagen content and by histological analysis. Generation of oxidants was evaluated by tissue luminol and lucigenin chemiluminescences (CL). Colitis caused significant increases in the colonic CL values, macroscopic damage scores, MDA, MPO and collagen levels, along with a significant decrease in tissue GSH level. Similarly, serum TNF-, IL-1, as well as LDH were elevated and AOC was reduced in the vehicle-treated colitis group as compared to control group. On the other hand, betulinic acid treatment reversed all these biochemical indices, as well as histopathological alterations induced by TNBS, suggesting that betulinic acid protects the colonic tissue via its radical scavenging and antioxidant activities. KEY WORDS: betulinic acid; colitis; oxidative damage; inflammation; trinitrobenzene sulphonic acid