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Celikbilek, Mehmet/0000-0001-8890-3885; /0000-0002-0636-4214 WOS: 000402467500012 PubMed: 28373116 Nephrotoxicity has been associated with nucleos(t)ide analogues other than telbivudine (LdT). This study investigated the potential effects of LdT and lamivudine (LAM) on renal function in an experimental rat model of gentamicin-induced acute nephrotoxicity. A total of 28 healthy Wistar albino rats were randomly divided into four experimental groups: negative control; positive control (PC); LdT; and LAM. Nephrotoxicity was induced by gentamicin in the LdT, LAM and PC groups. LdT and LAM were administered to two groups for 6 weeks starting on the ninth day. Blood samples were collected weekly and cystatin C levels were measured by ELISA. Animals were sacrificed on the 50th day and the kidneys were removed for histological examination. Serum cystatin C levels differed significantly between the LdT and LAM groups (P < 0.007) and between the LdT and PC groups (P < 0.001). Renal function was significantly improved in the LdT group at the start of antiviral treatment on Day 8 and at the end of treatment on Day 50 (P = 0.001 and 0.007). Glomerular injury, acute tubular necrosis and total injury score were significantly reduced in the LdT group relative to the PC and LAM groups upon histopathological examination. LdT was associated with significant improvements in renal function as measured by biochemical and histopathological methods. The acute kidney injury model data should be supported by clinical studies to suggest that LdT treatment may have advantages for patients with underlying chronic kidney disease receiving chronic hepatitis B treatment. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. Bozok University Scientific Research Project UnitsBozok University [2014TF-A126] This research was supported by the Bozok University Scientific Research Project Units [Project No. 2014TF-A126].

WOS: 000383902000015 PubMed: 27435174 Aim: Contrast medium-induced nephropathy is one of the major complications of intravenous contrast medium use. But its pathogenesis is unclear. Epithelial mesenchymal transition (EMT) is defined as the transformation of the primer epithelial cells to mesenchymal cells. EMT in tubular cells might cause tubulointerstitial damage. In this study, we investigated whether or not EMT has a role in radiocontrast-induced nephropathy. Radiocontrast medium might be triggering reversible EMT via serum and glucocorticoid-regulated kinase 1 (SGK 1). We investigated the effect of different concentrations of the contrast agent iopromide on human proximal tubule cell (HK-2) culture by measuring the level of SGK1, snail family zinc finger 1 (SNAIL1), connective tissue growth factor (CTGF), and collagen type I alpha 1 (COL1A1).Methods: We conducted a scratch assay and qPCR. HK-2 cells were cultured in the petri dishes/flasks and starved with serum-free medium. The 40, 20, and 10mg/mL doses of iopromide were administrated to cells. The scratches were photographed immediately and again at the 20th hour. The levels of gene expression of SGK1, SNAIL1, CTGF, and COL1A1 were measured using the real-time qPCR system at the end of the 24th hour.Results: Iopromide caused the breaking of intercellular connections, the disappearance of the cobblestone appearance of cells, and the migration of cells at the 20th hour in the scratch assay. It also increased the expression of SGK1, SNAIL1, CTGF, and COL1A1 genes.Conclusion: Our study concluded that certain important markers of EMT increase in different concentrations of the contrast agent. High osmolality might trigger EMT. The relationship between contrast agent and EMT has not been defined before. Further in vivo and in vitro studies are required. research foundation of Ondokuz Mayis University [PYO.TIP.1901.13.046] This study was supported by the research foundation of Ondokuz Mayis University [PYO.TIP.1901.13.046].

WOS: 000374903500025 PubMed: 26419593 Metastasis occurs due to migration of the cells from primary tumor toward other tissues by gaining invasive properties. Since metastatic invasion shows a strong resistance against conventional cancer treatments, the studies on this issue have been focused. Within this context, inhibition of migration and determination of the relationships at the gene level will contribute to treatment of metastatic cancer cases. We have aimed to demonstrate the impact of TGF-beta 1 and fluvastatin on human breast cancer (MCF-7) and human hepatocellular carcinoma (Hep3B) cell cultures via Real-Time Cell Analyzer (RTCA) and to test the expression levels of some genes (NDRG1, SGK1, TWIST1, AMPKA2) and to compare their gene expression levels according to RTCA results. Both of cell series were applied TGF-beta(1) and combinations of TGF-beta(1)/fluvastatin. Primer and probes were synthesized using Universal Probe Library (UPL, Roche) software, and expression levels of genes were tested via qPCR using the device LightCycler 480 II (Roche). Consequently, fluvastatin dose-dependently inhibited migration induced by TGF-beta 1 in both groups. This inhibition was accompanied by low level of SGK1 messenger RNA (mRNA) and high levels of NDRG1 and AMPKA2 mRNA. Thus, we conclude that fluvastatin plays an important role in reducing resistance to chemotherapeutics and preventing metastasis.

ozkaya, ozan/0000-0002-0198-1221 WOS: 000340259600020 PubMed: 24845105 Cisplatin is one of the commonly used anticancer drugs and nephrotoxicity limits its use. The aim of this study is to investigate the possible protective effect of creatine supplementation on cisplatin-induced nephrotoxicity. Sixty male Sprague-Dawley rats were divided into three groups: Group I: Cisplatin (n = 20) (7 mg/kg cisplatin intraperitoneal (i.p.) single dose), group II: Cisplatin + creatine monohydrate (n = 20) (7 mg/kg cisplatin i.p. single dose and 300 mg/kg creatine p.o. daily for 30 days starting on first day of cisplatin injection), group III: Control group (n = 20) (Serum physiologic, 2.5 mL/kg i.p.). Sacrifications were performed at first week and 30th day. Blood urea nitrogen (BUN) and serum creatinine levels, histopathological evaluation, mitochondrial deoxyribonucleic acid (mtDNA) common deletion rates, and body weights of rats were evaluated. A significant decrease in body weight, higher values of kidney function tests, histopathological scores, and mtDNA deletion ratios were observed in group I compared to control group at days 7 and 30 (p

AYGUN, CANAN/0000-0002-7955-5943 WOS: 000393323800007 PubMed: 28123334 Aim: The adequacy of 50 mcg folic acid supplementation given to low-birth-weight babies was investigated. The folate levels of the mothers and infants, and breastmilk, and the optimum dose for folic acid supplementation were also investigated. Material and Methods: After obtaining blood from 141 low-birth-weight infants on the 1st day of life for serum and red cell folate levels, the infants were randomly allocated into three groups according to the folic acid supplement dose. Forty-six infants were given 25 mu g/d folic acid, 39 were given 50 mu g/d folic acid, and 44 were given 75 mu g/d folic acid. Folic acid could not be given to 12 infants. Follow-up blood samples were obtained at the end of folic acid supplementation. Maternal samples for red cell and serum folate levels and breast milk folate levels were obtained within the first 48 hours and the samples for measuring breastmilk folate level were obtained on the 3rd day postnatally. The feeding modes of the infants, maternal folic acid intake, and details of neonate intensive care unit course were recorded. Results: The mean birth weight and gestational age of the infants were found as 1788.2 +/- 478.4 g and 33.5 +/- 2.9 weeks, respectively. The mean serum and red cell folate levels on admission were found as 21.2 +/- 12.2 ng/mL and 922.7 +/- 460.7 ng/mL, respectively. The mean maternal serum and red cell folate levels and the mean breast milk folate levels were found as 12.3 +/- 7.5 ng/mL, 845.5 +/- 301.4 ng/mL, and 30.6 +/- 33.0 ng/m, respectively. The breast milk folate levels of mothers who were supplemented with folic acid during pregnancy were significantly higher compared with mothers who were not supplemented with folic acid (p

WOS: 000389666700011 PubMed: 27079262 Objective: Previous studies have shown the relationship between lung development and glucocorticoids, but no studies have been conducted to investigate if a relationship exists between respiratory distress syndrome (RDS) and glucocorticoid receptor (GR) expression in preterm babies. We intended to investigate whether low GR expression is a risk factor for RDS. Methods: Forty-one preterm babies, 24-35 weeks of gestation, were included in the study following informed consent from the parents. The relative gene expression of GRalpha and GRbeta was measured in the peripheral mononuclear cells form cord blood samples. The demographic characteristics of the babies and the diagnosis of RDS were recorded. Results: RDS was more frequent in the group with low GRalpha expression: 12 (60%) in the GRalpha-I group and 6 (28%) in the GRalpha-II group (p = 0.043). Oxygen use with a hood, time to reach full enteral feeds and the duration of neonatal intensive care unit stay was shorter, and nosocomial sepsis episodes and number of erythrocyte transfusions were less in the GRbeta-I group. Higher hospital costs were found in the GRbeta-II group. Conclusions: Less RDS development, and better clinical follow-up was observed in premature babies with higher GR expression.

WOS: 000367771200014 PubMed: 26882815 Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by the release of inflammatory mediators. The aim of this study was to compare serum levels of pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) in patients with acute exacerbations of COPD with those of a healthy control group. Methods: The study included 107 men and 19 women, with mean age of 66.5 (32 - 87) years who were diagnosed with acute COPD exacerbations and 48 healthy individuals as a control group. The serum PTX3 and hs-CRP levels were measured and pulmonary function tests were performed. Results: The mean serum level of the hs-CRP was 39.56 mg/L (10.10 - 262), and it was higher in the COPD group than in the control group (p < 0.0001). The hs-CRP levels increased in accordance with the severity of the COPD (p < 0.0001). The serum PTX3 level was 0.52 pcg/dL (0.42 - 0.56) in acute exacerbations. There was a correlation between the PTX3 levels and the pulmonary function tests, including FEV1, FVC, and FEV1/FVC (r = 0.317, p < 0.001; r = 0.385, p < 0.0001, and r = 0.248, p = 0.001, respectively). Conclusions: The short pentraxin hs-CRP is elevated in COPD patients with acute exacerbations and correlates with the severity of the disease compared with the long pentraxin PTX3. These results support the idea that hs-CRP can be used as an earlier determinant of inflammation in COPD acute exacerbations and that PTX3 cannot be used as a marker of acute exacerbation and disease severity. Ondokuz Mayis University Research FundOndokuz Mayis University [PYO. TIP.1901.11.005] This study was supported by grants from the Ondokuz Mayis University Research Fund, project number PYO. TIP.1901.11.005.

OZET Roziglitazon; Tip II diabet tedavisinde kullanilan tiazolidinedion grubu bir ilactir. Bu grup ilaclar, karbonhidrat ve lipid metabolizmasini kontrol eden genlerin ekspresyonu¬nun duzenlenmesinde gorev alan peroksizom proliferator aktive reseptor-gama (PPAR-gama)’nin ligandi olarak rol oynarlar. Telomer; kromozom uclarinda bulunan ozellesmis DNA ve protein kompleksinden olusmaktadir. Omurgalilarda telomerik DNA, TTAGGG gibi, guaninden zengin dizelerden olusur. Normal hucrelerde, her DNA replikasyon per¬yodunda, telomer 50–150 baz kisalir. Tamir edilemeyen oksidatif DNA hasari da bu te¬lomer kisalmasina katkida bulunabilir. Literaturde, roziglitazonun telomer uzunluguna etkisini gosteren bir calisma bulunmamaktadir. Bu nedenle, calismamizda roziglitazonun telomer uzunluguna etkisini arastirmayi amacladik. Calismada 7–8 haftalik, 248-275 g arasinda, 16 tane erkek Sprague-Dawley cinsi rat kullanildi. Ratlar; her grupta dort tane olacak sekilde dort gruba ayrildi ve 14 gun boyunca 0, 0,5, 1,0 ve 2,0 mg/kg dozlarinda roziglitazon oral yoldan uygulandi. Rat karaciger, ince bagirsak, pankreas dokulari ve lenfositlerinden genomik DNA izolasyonu yapildi. Numunelerde genom sayisini belir¬leyebilmek icin tek kopya gen olarak 36B4 geni secildi. 36B4 genine spesifik primerle¬rin kullanildigi Q-PCR ile bir rat dokusundaki genom kopya sayisi bulundu. Rat genom standardi olarak kullanilan bu numune tum numunelerdeki genom sayisini bulmak icin kullanildi. Tum numunelerde telomer (T) ve 36B4 (S) icin kantitatif PCR yapildi. Iki ca¬lismada ile elde edilen urunler birbirine oranlarak her numune icin T/S orani daha sonra da bir kalibrator numune kullanilarak relatif T/S orani hesaplandi. Ayrica 10,2 kb telo¬mer standardi kullanarak numunelerin telomer uzunluklari kilobaz olarak da hesaplandi. Farkli roziglitazon dozlari verilen numuneleri kontrol grublari ile karsilastirildigimizda telomer uzunlugu acisindan istatistiksel olarak anlamli bir fark bulamadik (p>0,05). Bu sonuc, roziglitazonun farkli rat dokularinda telomer kisalmasina yol acmadigini gostermektedir. Research on the effect of rosiglitazon on telomere dynamics with molecular methods in rats ABSTRACT Rosiglitazone that is a drug for the treatment of type II diabetes mellitus, belong to the class of thiazolidinediones. Drugs of this class act as ligands for the peroxisome prolif¬erator-activated receptor-gamma (PPAR-gamma), which is involved in the regulation of genes controlling carbohydrate and lipid metabolism. Telomeres are composed of spe¬cialized DNA and protein complexes. Telomeric DNA consist of guanine-rich sequences, such as TTAGGG in vertebrates. In normal cells, telomeres shorten by ~50–150 bp with each round of DNA replication. In addition to this, unrepaired oxidative DNA damage can also contribute to telomere shortening. There is no study that shows the effect of rosiglitazone on telomere length in literature. Because of this, we aimed to research on the effect of rosiglitazone on the telomere length in our study. We used sixteen male Sprague- Dawley rats that at 7-8 weeks of age and weighing 248–275 g in our study. The rats were divided into four groups, four rats in each group, and dosed once a day for 14 days by oral gavage with doses of 0.0, 0.5, 1.0, and 2.0 mg/kg rosiglitazone. Genomic DNA was extracted from rat liver, small intestine, pancreas tissue and lymphocytes. The 36B4 genewas chosen as single copy gene for determine the number of genom in the samples. The number of genome copies were found in a rat tissue by qPCR that is used the 36B4 gene-specific primers. This sample, that is used as rat genom standarts, was used for find the number of genome in all samples. The qPCR was performed for telomere (T) and 36B4 (S) in all samples. The T / S ratio was calculated by the ratio of the products derived from two studies to each other, and then the relative T / S ratio was calculated by using a calibrator sample for each sample. In addition, telomere lengths of the samples were also calculated as kilobase by using 10,2 kb long telomere standard. We did not found statistically any significant difference between doses of rosiglitazone and control groups for telomere length (p>0.05). This result has showed that rosiglitazone doesn’t lead to telomere shortening. J. Exp. Clin. Med., 2011; 28:162-167

Akalin, Ibrahim/0000-0002-7487-4603; Demir, Selim/0000-0002-1863-6280 WOS: 000297798600005 PubMed: 22119868 The aim of the present study was to evaluate the potential of Turkish propolis extracts if they prevent or protect foreskin fibroblast cells against hydrogen peroxide (H2O2)-induced oxidative DNA damage. Hydrogen peroxide (40 mu M) was used as an inducer of oxidative DNA damage. The damage of DNA was evaluated by using the alkaline single cell gel electrophoresis (comet) assay. Turkish propolis extracts at concentrations of 25, 50, 75 and 100 mu g/ml were prepared by ethanol. Anti-genotoxicity was assessed before, simultaneously, and after treatment of propolis extract (50 mu g/ml) with H2O2. The results showed a significant decrease in H2O2-induced DNA damage in cultures treated with propolis extract. The antioxidant activity of phenolic components found in propolis may contribute to reduce the DNA damage induced by H2O2. Our findings confirmed the chemopreventive activity of propolis and showed that this effect may occur under different mechanisms. Foundation of Scientific Research of Karadeniz Technical University, Trabzon, TurkeyKaradeniz Teknik University [2008.114.001.5] This study was supported by Foundation of Scientific Research of Karadeniz Technical University, Trabzon, Turkey (No: 2008.114.001.5). We wish to thank Prof. Murat Erturk (Department of Medical Microbiology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey) for the helpful insights and for kindly providing the foreskin fibroblast cell line.

WOS: 000293238300004 PubMed: 21347604 We proposed to assess serum antioxidant vitamins and magnesium (Mg) levels in patients with fibromyalgia (FM) in comparison to healthy controls. Additionally, the association between the serum antioxidant vitamins, magnesium levels, and clinical parameters in FM patients was also investigated. Forty female patients, aged between 30 and 50 years, were diagnosed with FM according to ACR-1990 criteria, and 40 healthy controls were included in the present study. Socio-demographic characteristics of participants, accompanying symptoms, and number of tender points (TP) of the patients were recorded. The intensity of pain was measured using the visual analogue scale (VAS). The functional status and depression levels were evaluated with Fibromyalgia Impact Questionnaire (FIQ) and Beck Depression Inventory (BDI), respectively. Serum vitamins A, C, and E and Mg levels were measured. There were no significant differences in the levels of vitamins A, C, and E and Mg between control subjects and patients with fibromyalgia (p > 0.05). In addition, no statistically significant correlations were found between mean levels of serum vitamins A, C, and E, and Mg and number of TP, scores of VAS, FIQ, and BDI in patients with FM (p > 0.05). According to the results of this study, it was asserted that other complex mechanism may play an important role in the pathophysiology of FM without plasma antioxidant vitamins and Mg levels.

Summary Background. Several different laser types are used in cutaneous surgery. The neodymium:yttrium–aluminium–garnet (Nd:YAG) and frequency-doubled Nd:YAG (KTP, potassium titanyl phosphate) lasers are widely used in dermatology. Objectives. To investigate the possible genotoxic effects on fibroblasts of irradiation with a 1064-nm Nd:YAG laser and a 532-nm KTP laser. Methods. Fibroblast cell cultures were exposed to each of the lasers, using 10-mm spot size at 60 ms pulse duration with 10, 20, 40 J/cm2 and 3, 6, 12 J/cm2 fluences, respectively. Fibroblasts in passages 1–6 were used. During laser irradiation, 96-well microplate cultures were kept on a cooling block and transported on ice and in the dark, and processed immediately for single-cell gel electrophoresis (SCGE) assay (also known as a comet assay). Results. DNA damage was determined by computerized assessment of comet assay. There was increasing damage with increasing numbers of passages. For the Nd:YAG laser, the greatest damage occurred on passages 5 and 6, whereas the greatest damage appeared at passages 3 and 4 for KTP and returned to baseline at passages 5 and 6. Damage also increased with each dose increment for both wavelengths. At the highest dose for both wavelengths (Nd:YAG 40 J/cm2 and KTP 12 J/cm2), damage was higher with the Nd:YAG laser. Conclusions. Different patterns of cellular damage were seen for different cell-culture passages, treatment doses, and laser wavelengths. These dose ranges are generally used for the treatment of vascular and pigmented lesions and for rejuvenation purposes. As replicative ageing or cell senescence is one of the critical factors determining the extent of cell damage induced by laser therapy, these results may have important implications for clinical practice.

Objective: The aim of this study was to investigate Legg-Calvé-Perthes disease (PD) pathogenesis by comparing absolute circulating endothelial progenitor cell (EPC) counts, serum levels of vascular endothelial growth factor-A (VEGF-A) and immunoglobulins between PD patients and controls.Methods: The study included 28 PD cases (mean age: 8±3.8) and 25 healthy age-matched control subjects. EPC, serum VEGF-A and immunoglobulin levels were measured in peripheral blood samples. Comparisons and correlation analysis were performed.Results: In the PD group, 17 subjects were in the fragmentation stage and 11 in the healing stage. Four patients had bilateral disease and 14 had hypogammaglobulinemia. Median EPC count of the PD group was 80 and was significantly higher than those of the control group (p=0.011). No significant difference was determined in serum VEGF-A levels (p=0.354). EPC count were inversely correlated with serum IgG levels of the PD group (r=0.403, p=0.03). Absolute EPC count was also significantly higher in the fragmentation stage than in the healing stage and were also greater in bilaterally affected than in unilaterally affected patients. Circulating EPC count was correlated to the serum VEGF-A levels in patients with fragmentation stage of PD (r=0.605, p=0.01) and in those with hypogammaglobulinemia (r=0.599, p=0.001).Conclusion: High EPC count at the fragmentation stage of PD and relatively higher counts in bilateral disease suggest that EPC may be a valuable marker in the diagnosis and follow-up of PD. Additional studies are needed to explain the strong correlation between EPC and serum VEGF-A level in the fragmentation stage and in the presence of hypogammaglobulinemia., Amaç: Bu çalışmada Legg-Calvé-Perthes hastalığının (PH) etiyopatogenezinin aydınlatılması amaçlanmıştır. Bu amaca yönelik olarak Perthes hastaları ile kontrol grubu olgularında dolaşımdaki endotelial progenitör hücre (EPH) sayısı, serum vasküler endotelial büyüme faktörü-A (VEBF-A) ve immünoglobulin düzeyleri karşılaştırıldı.Çalışma planı: Çalışmaya 28 PH olgusu (ortalama yaş: 8±3.8) ve yaşları eşleşen 25 sağlıklı kontrol olgusu dahil edildi. Periferik venöz kan örneklerinde EPH, serum VEBF-A ve immünoglobulin düzeyleri ölçüldü. Karşılaştırma ve korelasyon analizleri uygulandı.Bulgular: PH grubundaki olguların 17’si fragmantasyon, 11’i ise iyileşme döneminde idi. Hastalık 4 olguda bilateral iken, 14 hastada hipogamaglobulinemi mevcuttu. PH grubundaki medyan EPH sayısı 80 olup kontrol grubuna göre anlamlı derecede yüksekti (p=0.011). Serum VEBF-A düzeylerinde anlamlı farklılık saptanmadı (p=0.354). PH grubunda EPH sayısı serum IgG düzeyi ile tersine korele idi (r=-0.403, p=0.03). Mutlak EPH sayısı fragmantasyon dönemindeki hastalarda, iyileşme dönemindekilerden; bilateral hastalığı olanlarda ise unilateral olanlardan anlamlı olarak yüksekti. Dolaşımdaki EPH sayısı Perthes hastalığının fragmantasyon safhasında (r=0.605, p=0.01) ve hipogamaglobulinemi varlığında (r=0.599, p=0.001) serum VEBF-A düzeyi ile korelasyon göstermekteydi.Çıkarımlar: Fragmantasyon evresindeki hastalarda görülen yüksek EPH sayısı ve bilateral tutulumu olan hastalarda nispeten daha yüksek bulunan EPH sayısı, PH’nin takibinde değerli bir gösterge olabilir. Hastalığın fragmantasyon evresinde ve hipogamaglobulinemi varlığında EPH sayısı ve serum VEBF-A düzeyi arasındaki güçlü korelasyonu açıklamak için daha fazla çalışma yapılmasına ihtiyaç vardır..

Objective: The median values of double test which is commonly used for Down Syndrome screening show diversity between countries. In this study, we aimed to investigate the possible differences in corrected multiplies of median (MoM) values of individiuals between the two cities of the same geographic region.Methods: Blood samples for double test analysis, sent from Corum and Samsun, were studied in the same laboratory. Results of double test analyses were retrospectively evaluated. Mann-Whitney U test was used for comparison of corrected MoM values of free human chorionic gonadotropin (f-β hCG) and pregnancy-specific plasma protein-A (PAPP-A) according to gestational age. Results were given as median (minimum-maximum) values. The p Results: The corrected f-β hCG values obtained from Corum and Samsun were as follows: 0.75 (0.24-2.11, n=28), 0.85 (0.21-2.95, n=143) (p=0.378) in 10Conclusion: The MoM values of f-β hCG tests, derived from individuals from Corum and Samsun, both located in the Central Black Sea Region, were found to be different. This finding indicates that for double test analysis, different median values may be used for patients from different cities.

Objective: The median values of double test which is commonly used for Down Syndrome screening show diversity between countries. In this study, we aimed to investigate the possible differences in corrected multiplies of median (MoM) values of individiuals between the two cities of the same geographic region. Methods: Blood samples for double test analysis, sent from Corum and Samsun, were studied in the same laboratory. Results of double test analyses were retrospectively evaluated. Mann-Whitney U test was used for comparison of corrected MoM values of free human chorionic gonadotropin (f-? hCG) and pregnancy-specific plasma protein-A (PAPP-A) according to gestational age. Results were given as median (minimum-maximum) values. The p

Rosiglitazone (RSG), a member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by increasing insulin sensitivity. The therapeutic mode of action of RSG involves its activity as a highly selective and potent agonist for peroxisome proliferator-activated receptor-g. Although other drugs in this class have displayed unacceptable hepatotoxicity, RSG was approved for human use. The package insert indicates that RSG has minimal genotoxicity, but information on the genotoxicity of RSG is not available in the published literature. In this study, we used the single cell gel electrophoresis (SCGE)/Comet assay to investigate the DNA damage in peripheral blood and liver cells of rats treated with RSG. Sixteen male Sprague-Dawley rats were randomly distributed into four groups, and dosed daily by oral gavage with 0.0, 0.5, 1.0, and 2.0 mg/kg/day RSG. The rats dosed with 2.0 mg/ kg/day RSG received an � 10-times the area under the curve concentration of the maximum recommended human daily dose. After 14 days of treatment, the rats were euthanized, and peripheral blood and liver were collected and processed for the Comet assay. A dose-dependent increase in DNA damage (as assessed by % tail DNA and Olive Tail Moment) was observed in the hepatocytes of RSG-treated groups, with significant increases detected between rats treated with all the doses of RSG and the control, and between rats treated with different RSG doses (P < 0.05 – P < 0.0001). In contrast, DNA damage was detected in peripheral blood lymphocytes only in rats treated with the higher RSG doses (1.0 and 2 mg/kg/day). Taken together, the data indicate that RSG is able to induce primary DNA damage in rats, with greater damage being detected in liver cells than lymphocytes. Environ. Mol. Mutagen. 47:718–724, 2006. V C 2006 Wiley-Liss, Inc.

WOS: 000232747600017 PubMed: 16019038 Behcet's disease (BD) was originally described by Turkish dermatologist, Hulusi Behcet in 1937. BD is an inflammatory disorder of unknown cause, characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. All these common manifestations are self-limiting except for ocular attacks. The aims of this study were to assess whether BD patients have more genotoxicity than healthy controls and whether colchicine (COL) treated BD patients are different from those not using COL in terms of genotoxicity. A few dozens of methods have been developed and used for the assessment of genotoxicity. The most popular method is based on single cell gel electrophoresis (COMET assay) in alkaline condition. After electrophoresis, captured images are subjected to digital image analysis to find the values for percent tail DNA from comet assay parameters consistent with genotoxicity. COMET assay was performed in isolated lymphocytes from 42 COL treated Behcet's disease patients, 9 BD patients not using COL, and 36 healthy controls. In the COL-BD patients and non-COL-BD patients, the mean age (range 14-56 years) and mean disease duration (range 0.5-24 years) did not differ between the two groups. We found statistical differences in percent tail DNA between BD and the healthy controls (13.38 +/- 9.58 versus 2.77 +/- 1.45, P < 0.0001). No difference in percent tail DNA was observed between users and non-users of COL, whereas it was more different in inactive BD patients than active ones (19.75 +/- 10.49 versus 11.83 +/- 8.79, P < 0.05, respectively). Genotoxicity, as assessed by COMET assay, is increased in BD patients. These results suggest that genotoxicity is associated with BD itself rather than COL use. (C) 2005 Elsevier B.V. All rights reserved.

WOS: 000188879200004 PubMed: 15310006 Background: The role of leptin in polycystic ovarian syndrome (PCOS) is unclear. We investigated the relationship between serum leptin levels, body composition and insulin resistance in polycystic ovarian syndrome (PCOS). Methods: We analyzed differences between 27 patients with PCOS and 25 control subjects in serum glucose and leptin levels, insulin resistance, body fat mass, lean body mass, and water volume. Results: Serum leptin was significantly correlated with basal insulin levels, BMI and IR in both groups (P

WOS: 000185035700008 PubMed: 12906034 Increased serum urate concentration is a frequent finding in patients with hypertension. Since hyperuricemia is associated with obesity, renal disease. hyperlipidemia, and atherosclerosis. whether or not serum urate is a cardiovascular risk factor per se has remained elusive. The Subjects were 2 10 Turkish male and 2 10 female adults over 20 years of age. None had diabetes mellitus, endocrine diseases. or renal or hepatic disease, and those receiving antihypertensive drugs systemic corticosteroids, or lipid-lowering drugs were excluded. Height. weight. blood pressure, serum glucose, lipid profiles, serum insulin. DHEA-SO4, and leptin were measured in the morning after an overnight fast. Women had significantly higher mean leptin (20.3 +/- 0.88 ng/mL vs 5.78 +/- 0.39 ng/ mL P < 0.001) and lower mean uric acid (248.03 +/- 4.76 mumol/L vs 311.6 +/- 5.35 mumol/L. P < 0.001). triglyceride (1.42 +/- 0.06 mmol/L vs 1.61 +/- 0.06 mmol/L, P < 0.001), and DHEA-SO4 (3.02 +/- 0.17 mumol/L vs 4.43 +/- 0.19 mumol/L, P < 0.001) concentrations than men, even when adjusted for BMI. On univariate correlation analysis, leptin showed the strongest association with BMI in both sexes and also correlated significantly with BMI. insulin. uric acid, glucose. total cholesterol, and triglycerides in males and BMI, insulin, uric acid, total cholesterol, apo B, and creatinine in females after adjustment for age and BMI. A statistical model containing creatinine, leptin, insulin, and triglycerides accounted for 34% of the variance in Serum uric acid levels in men, whereas another consisting of creatinine, triglycerides, leptin, SBP, and insulin explained 42% of the variance in serum uric acid in women. The present study suggests that leptin could be one of the possible candidates for the missing link between obesity and hyperuricemia. Our study may also suggest that hyperuricemia is not only a metabolic end product but also a marker of a major pressor or pathogenic mechanism underlying the hypertension in obesity.

The last decade has witnessed many exciting scientific publications associated with site-selective reactions of small chemical molecules with imperfectly matched DNA. Typical examples are carbodiimide, hydroxylamine, potassium permanganate, osmium tetroxide, chemical tagging probes, biotinylated, chemiluminescent and fluorescent probes, and all of them selectively react with imperfectly matched DNA. More recently, some therapeutic agents including DNA intercalating drugs and groove binders have been found to promote the in vivo repair system to recognize and repair the mismatch more effectively. The results have established a novel method for detection of mismatches. Development of new chemical reactions for detection of imperfectly matched DNA and mutations is a rapidly growing field and has attracted significant interest of scientists from both chemical and biological fields and it is the main focus of this review.

WOS: 000344075800003 PubMed: 25335733 N-myc downstream-regulated gene 1 (NDRG1) is defined as metastasis suppressor and can be downregulated in many types of cancers, and reported to be an indication of tumor progression in hepatocellular carcinomas. Several in-vivo and in-vitro studies have demonstrated that iron chelators such as Desferrioxamine (DFO) and 1-10 Phenanthroline (PHEN) are effective antitumor agents. It is suggested that these chelators deliver their antitumor activity by acting on the NDRG1 gene expression. It remains unclear why NDRG1 gene expression affects the tumors differently, or becomes affected differently. We consider that this different effect might be caused by variants. Based on this information, we developed specific primers and probes for NDRG1 mRNA variants using bioinformatics analysis, and investigated how DFO and PHEN affected the dynamics of NDRG1 variant on the cell lines of Human Breast Adenocarcinoma (MCF-7) and Hepatocellular Carcinoma (HepG2) that demonstrate opposite action for the relationship NDRG1-metastasis. We administrated various doses of DFO and PHEN into the cells to monitor cell vitality and proliferation with Real time Cell Analyzer. We analyzed the gene expression levels of study groups with Quantitative RT-PCR as well as relative gene expression. Variants of NDRG1 mRNA were transcriptionally regulated after HepG2 and MCF-7 cells were treated by iron chelators, resulting in domination of NDRG1 mRNA Variant 1 (V1) in the HepG2 calls and domination of NDRG1 mRNA Variant 2 (V2) in the MCF-7 cells. Anti-proliferative and cytotoxic effects were observed in the MCF-7 cells whereas an increased proliferation was present in the HepG2 cells. Ondokuz Mayis UniversityOndokuz Mayis University; [OMU PYO. TIP.1904.11.028.26] This study was supported by Ondokuz Mayis University. The Project number was OMU PYO. TIP.1904.11.028.26.

Erdemli, Haci Kemal/0000-0002-3399-4676; Kocabas, Ramazan/0000-0002-7861-258X WOS: 000343674700012 PubMed: 25110805 Objective: To evaluate the utility of serum biomarkers in the diagnosis of preeclampsia (PE) and also investigate possible correlation with pathogenesis of PE. Methods: Maternal serum concentrations of heme oxygenase-1 (HO1) and N-myc downstream-regulated gene 1 (NDRG1) were measured at 27-34 weeks of gestation in a case-control study of 33 pregnant women diagnosed with PE and in 43 normotensive pregnant women without proteinuria. The Mann-Whitney U test and Spearman's correlation were used for statistical analysis. Results: The median serum HO1 level was found to be significantly higher in the PE group [76.7 ng/ml (23.4-445.7)] than control group [55.9 ng/ml (3.7-354.3)] (p = 0.006). Positive correlation was found between HO1 levels with presence of PE (r = 0.316, p = 0.005). There was no significant difference in NDRG1 values between the two groups (p = 0.226). Conclusions: Serum HO1 levels were found to be increased in patients with PE compared with normotensive pregnant women.

AYGUN, CANAN/0000-0002-7955-5943 WOS: 000339860800004 PubMed: 25008013 Background: Previous studies have shown the relationship between in utero lung development and vitamin D [25(OH)D], but there have been no studies to investigate whether vitamin D deficiency is a risk factor for respiratory distress syndrome (RDS) in preterm babies. Objectives: In this study, we investigated if 25(OH)D deficiency is a risk factor for RDS. Methods: One hundred fifty-two preterm newborns, born at 29-35 weeks gestational age, were included in the study following informed consent from the parents. Peripheral blood samples were collected within the first 24 hours of life and 25(OH)D levels were measured by liquid chromatography-tandem mass spectrometry. Demographic characteristics of the babies and the diagnosis of RDS were recorded. Results: In 64% of preterm infants, 25(OH)D levels were compatible with severe deficiency (

The endoplasmic reticulum (ER) is related to the various signal routes that are activated in unfolded protein response (UPR). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expressions demonstrate UPR activity. In this study, we investigated the UPR gene expressions in larynx epidermoid carcinoma (HEp2) to which dexamethasone (dex) was applied. HEp2 cells were administered for 48 h with different combinations using 0.1 microM and 1 microM dex, 1 mM phenyl butyric acid (PBA) and 100 ng/ml lipopolysaccharide (LPS). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expression was determined using quantitative RT-PCR. The Grp78, MTJ1 and HMOX1 gene expression increased with the administration of 1 microM dex. CHOP expression, on the other hand, decreased with 0.1 microM dex. When dex was combined with LPS, nearly all gene expressions decreased. The increase in Grp78, Grp94, HMOX1 and MTJ1 gene expression was greater in groups in which dex was administered in combination with PBA than in groups in which dex was administered alone. Dex in low dose (0.1 microM) caused a decrease in CHOP expression in HEp2 cells and an increase in Grp78 expression, in particular. The changes in UPR genes expressions may lead to the extended survival of the cells.

Background: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. Methods: Blood samples were collected nationwide in 28 laboratories from the seven regions (?400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). Results: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and ?-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. Conclusions: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population. © by De Gruyter 2014., Applied Scientific Research Fund: :24256003:2012-2014 Japan Society for the Promotion of Science, Acknowledgments: This study was supported by Research Fund of Uludag Universty (UAP(T)-2011/48), IFCC C-RIDL, Scientific Research Fund (No:24256003:2012-2014) provided by the Japan Society for the Promotion of Science, Abbott Diagnostics and Becton Dickinson. We had invaluable input from the IFCC C-RIDL and the Turkish National Biochemical Association. We are very grateful to Uludag University Central Laboratory, We are thankful to David Ambruster from Abbott Diagnostics for his kind cooperation to realize this study. The final manuscript was edited with generous support by Prof. A. Myron Johnson.

WOS: 000337094900112 PubMed: 24622883 Histone deacetylase (HDAC) inhibitors, such as trichostatin A (TSA), and iron chelators, including deferoxamine (DFO) and phenanthroline (PHEN), appear to have anticancer effects. We hypothesized that the HDAC inhibitors and iron chelators would be synergistic with their effect on breast cancer cell line MCF7, because the HDAC inhibitors increase glucose-regulated protein 78 (Grp78) and the iron chelators reduce its expression. Although the administration of TSA alone resulted in a dose-related decrease in the cell index, it did not have an antiproliferative effect except the 62.5 and 500 nM of TSA. However, all doses of TSA produced a cytotoxic effect from the initial hours when combined with 150 mu M of DFO and 25 mu M of PHEN. DFO and PHEN downregulated Grp78, Grp94, and MRP1 expressions and upregulated CHOP and HO-1 expressions. TSA upregulated all the genes in various rates when used alone but resulted in decreased expression levels when combined with DFO and PHEN. Increased HDAC-1 levels in the Grp78 promoter region indicated that DFO and PHEN either promoted binding of HDAC-1 to this region or inhibited its detachment. We determined that the reduction of increased Grp78, Grp94, HO-1, and MRP1 expressions, which appears to inhibit the chemotherapeutic effect of TSA, through the combination with DFO or PHEN will contribute to the anticancer effect. Ondokuz Mayis UniversityOndokuz Mayis University; [PYO.TIP. 1901 09 001] This study was supported by the Ondokuz Mayis University. The project number was PYO.TIP. 1901 09 001.

WOS: 000347538100004 PubMed: 25347557 Fluvastatin (FLU) prevents the conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonic acid by inhibiting HMG-CoA reductase and decreases cholesterol level. Although the effects of FLU treatment on several cancer types through many mechanisms have been identified, its relationship with unfolded protein response and apoptosis has not been clearly understood. In this recent study, we aimed to investigate the cytotoxic effect of Fluvastatin on MCF-7 cells and define the transcriptional regulation of specific genes during the occurrence of this cytotoxic effect. We administered 0.62, 2.5, 5, and 40 mu M FLU on MCF-7 cells singly and in combination with 2-deoxyglucose (2-DG), and we monitored cell viability and proliferation for 48 hours using real-time cell analyzer system (xCELLigence). At the same time, we measured the mRNA expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein, homologous protein (CHOP), caveolin-1 (CAV1), NDRG1 Variant 1 and Variant 2, HMOX1, SGK1, and prostate apoptosis response-4 (PAR4) genes using quantitative real-time polymerase chain reaction (LightCycler 480 II). We accepted GAPDH gene and control groups as the reference gene and calibrator, respectively. We performed relative gene expression analyses of the study groups using the QIAGEN 2009 Relative Expression Software Tool (REST). FLU revealed an antiproliferative and cytotoxic effect on MCF-7 cells, while causing the transcriptional regulation of many genes. Of these genes, the mRNA expressions of CHOP, heme oxygenase 1 (HMOX1), N-myc downstream-regulated gene 1 (NDRG1) V1, and NDRG1 V2 increased. On the other hand, the mRNA expression levels of SGK1 and CAV1 decreased. The antiproliferative effects of FLU may be related to the decreased expression levels of SGK1 and CAV1.

ozkaya, ozan/0000-0002-0198-1221 WOS: 000340259600019 PubMed: 24937012 Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69M x 10(-5) at 24th hour and 3.93M x 10(-6) at 48th hour. IC50 dose for pioglitazone was 1.61M x 10(-3) at 24th hour and 2.85M x 10(-4) at 48th hour. Although cells were treated the dose of 40,225mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity. Ondokuz Mayis UniversityOndokuz Mayis University [PYO.TIP.1901.10.014] The authors report no declarations of interest. This study was supported by grants from the Ondokuz Mayis University Research Fund with the number PYO.TIP.1901.10.014

Cosar, Arif Mansur/0000-0002-4472-2895; Cosar, Arif Mansur/0000-0002-4472-2895 WOS: 000086013400008 PubMed: 10720895 The pathogenesis of acute renal failure may involve, among other causes, ischemia, vascular congestion, arachidonic acid pathways, and reactive oxygen metabolites. The aim of this study is to evaluate the effects of pentoxifylline and vitamin E on the prevention of experimental acute renal failure induced by glycerol. Eighty-five Sprague-Dawley rats weighing 170-230 g were included in the study. The rats were randomly divided into four groups: group 1 was given 1 ml saline; group 2, glycerol; group 3, glycerol plus vitamin E, and group 4, glycerol plus pentoxifylline. Extent of histological renal tubular necrosis and regeneration in each animal were graded, Blood urea nitrogen, serum creatinine, and creatine kinase concentrations were measured. Mean blood urea nitrogen and serum creatinine concentrations and tubular injury scores were significantly lower in group 1 than in groups 2-4 (p < 0.001), but there were no significant differences among groups 2-4, We conclude that postinsult administration of vitamin E and pentoxifylline does not have a beneficial effect on prevention and severity of acute renal failure and that controlled, multicenter studies involving a large number of patients are needed to clarify this subject. Copyright (C) 2000 S. Karger AG, Basel.

WOS: 000083376900012 PubMed: 10560791 Studies in various ethnic groups have shown contradictory evidence on the association of: the angiotensin converting enzyme (ACE) insertion/ deletion (I/D) polymorphism with essential hypertension. We conducted a case-control study in Samsun, Turkey, to examine the association between ACE genotype, ACE serum activity, and blood pressure. Serum ACE activity was measured and ACE I/D polymorphism performed in 165 hypertensive and 143 normotensive subjects. Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR), PCR primers were flanking the polymorphic region in intron 16 of the ACE gene. The distribution of the DD, ID, and II ACE genotypes was 65, 77, and 23 in hypertensive patients and 42, 82, and 19 in normotensive subjects (P > .05). The estimated frequency of the insertion allele was 0.37 in hypertensive and 0.42 in normotensive subjects. Nevertheless, sensitivity analysis, based on positive family history and severity of hypertension, suggested that significant associations existed between more homogeneous groups of hypertensives and normotensives (P < .05). ACE genotype influenced ACE activity and the highest level was in DD genotype, being the lowest in II genotype. ACE serum levels were significantly higher in hypertensives as compared with normotensives (P < .01). A modest correlation was observed between blood pressure and ACE among hypertensive persons (r = 0.25, P < .05) and this did persist in multivariate analysis (P < .05 for systolic blood pressure and P < .005 for diastolic blood-pressure). These data suggest that ACE DD genotype may have predisposing effects on severe hypertensives and cases with positive family history, and that ACE may be one of the independent factors on hypertension. (C) 1999 American Journal of Hypertension, Ltd.

Behcet’s disease (BD) related amyloidosis is relatively rare. Serum amyloid A protein (SAA) protein gene polymorphism is one of the factors implicated in the pathogenesis of AA type amyloidosis. The aim of this study is to investigate SAA1 gene polymorphism in different patient groups: (1) BD related amyloidosis, (2) BD without amyloidosis, and (3) healthy controls. One hundred eleven patients from three main groups were included in the study: (1) BD related amyloidosis (n = 9), (2) BD without amyloidosis (n = 39), and (3) healthy controls (n = 63). Homozygous α/α is present in 78% of patients with BD and amyloidosis. The SAA1 α/α genotype is significantly more common among patients with BD and amyloidosis. This study demonstrated increased frequency of α/α genotype in BD related amyloidosis. To our knowledge, the relationship between α/α genotype and BD related amyloidosis was not studied previously. In conclusion, the SAA1 α/α genotype is a risk factor for amyloidosis in BD.

WOS: 000324374700060 PubMed: 23683570 Purpose: To investigate predictive powers of S100B and cell-free DNA (cfDNA) levels in patients in the intensive care unit (ICU) who have with intracranial hemorrhage (ICH) for prognosis. Methods: Ninety-nine patients diagnosed with ICH were included in the study. The blood samples were drawn on the day of admittance to ICU and again on the third day. Duration of stay in the ICU and mortality were recorded. Results: A positive correlation was determined between the values of S100B and cfDNA from both the analysis and the Acute Physiology and Chronic Health Evaluation II scores. For all patients, there was a positive correlation between the duration of stay in the ICU and the values of S100B and cfDNA on the third day. The levels of both S100B and cfDNA in patients who died in the ICU were significantly higher than of those who survived on the day of admittance. Conclusions: Both S100B and cfDNA values can be used as markers to predict the prognosis of ICU patients with ICH. However, S100B is more powerful for predicting the prognosis. (C) 2013 Elsevier Inc. All rights reserved. Ondokuz Mayis University Scientific Research FoundationOndokuz Mayis University This study was supported by the Ondokuz Mayis University Scientific Research Foundation.

WOS: A1996UX54000012 PubMed: 8828970 …

Our purpose in this study was to analyze telomere length and telomerase activity before and after eradication treatment in gastric mucosa in patients positive for H. pylori.There were two groups: a control group (n=17) and a study group (n=21). For H. pylori eradication, the patients were administrated proton pump inhibitor (PPI) + clarithromycin + amoxicillin or PPI + metronidazole + tetracycline + bismuth for 14 days. Telomere length was analyzed with RT-PCR and telomerase activity with PCR-ELISA on biopsy specimens from the antrum. The result p0.05 was considered significant.Prior to eradication, there was no significant difference between telomere lengths of the patient and control groups (2481.2±1823 and 2958.9±1345.7 bp, p=0.11, respectively). The telomere length of the study group became longer after eradication (before 2481.2±1823bp, after 3766.3±1608.8bp, p=0.01). Telomerase activity was not detected in either the patient or the control group.An increase in telomere length was observed with H. pylori eradication. This finding may indicate the importance of H. pylori eradication to avoid the development of gastric cancer.

AVCI, Bahattin/0000-0001-6471-6495 WOS: 000311201500030 PubMed: 22890828 Our purpose in this study is to analyze mitochondrial DNA (mtDNA) lesion frequencies and mtDNA(4977) deletion in HepG2 cells to examine the effects of ouabain on mtDNA. HepG2 cells were treated with 0.75, 7.5, 75, and 750 nM of ouabain for 24 h in the presence and absence of 10 mM 2-deoxyglucose (2-DG). The frequency of mtDNA(4977) deletions and mitochondrial lesions were determined by real-time polymerase chain reaction. A a parts per thousand yen1.2-fold change or greater was considered significant. Ouabain doses of 750, 75, and 7.5 nM alone increased the frequency of mtDNA(4977) deletions 1.39, 1.92, and 1.44 times, respectively. The 750 and 75 nM ouabain doses combined with 2-DG increased the mtDNA(4977) deletion frequency 4.94 and 1.57 times, respectively. The 750 and 75 nM ouabain doses alone increased the mtDNA lesion frequency 2.5 and 1.5 times, respectively. The 750 nM ouabain dose combined with 2-DG increased the mtDNA lesion frequency 2.28 times. The 7.5 nM ouabain dose alone and combined with 2-DG decreased the mtDNA lesion frequency 0.67 and 0.45 times, respectively. Ouabain alone and when combined with 2-DG increases mtDNA lesion and mtDNA(4977) deletion frequencies. This supports the thesis that ouabain creates oxidative stress and induces DNA damage and apoptosis. Ondokuz Mayis UniversityOndokuz Mayis University This study was supported by Ondokuz Mayis University Research Fund.

WOS: 000309986200001 Glucose regulated protein 78 (Grp78) is a chaperon which acts in the protein folding. Cell-surface Grp78 is present on the surface of different type cancer cells. There are evidences that acetylsalicylic acid (ASA) provides advantages when combined with other chemotherapeutic agents in cancer patients. Resistance is an important problem in cancer treatment and etoposide is a drug which develops resistance against itself. Our purpose in this study is to see how the ASA, either used alone or combined with etoposide, affect on the HepG2 cell viability and to investigate the relationship of this viability with the cell-surface Grp78. Thus 12 different groups were assigned. Control group, 0.5 mu g/ml etoposide group, 2.5, 5, 10 mM ASA groups, 10 mM 2-deoxyglucose (2-DG) + 0.5 mu g/ml etoposide group and the groups added to this group with 2.5, Sand 10 mM ASA respectively, 10 mM 2-DG +2.5 mM ASA group, 10 mM 2-DG + 5 mM ASA group, 10 mM 2-DG + 10 mM ASA group. MIT test was applied for the follow up of the viability of the cells. When the viability in etoposite group was %84.5, the viability in 2-DG+etoposit group was %75.4. This shows that 2-DG decreases the viability of the cells a little. Also, when ASA is applied alone or combined with 2-DG, it caused decrease in the cell viability but this effect was more significant when combined with 2-DG. When etoposide and ASA were combined, the decrease in high-dose viability was more significant. Cell surface Grp78 levels were higher in the group in which 2-DG and ASA were combined each other than the group in which ASA was applied alone. All these results show that cell-surface Grp78 is important for ASA showing its effect. New treatment protocols focused on the cell-surface Grp78 in cancer treatment can be revealed by further studies.

PubMed ID: 22757644, Ouabain is a cardiotonic steroid and specific inhibitor of the Na +/K+-ATPase. The relationship between ouabain treatment and the unfolded protein response (UPR) in cells is not precisely understood. Therefore, we studied the possible effects of ouabain on proliferation, apoptosis, and the UPR. HepG2 cells were cultured overnight and then treated with various concentrations of ouabain (0.75 to 750nM) in the absence or presence of 10mM 2-deoxyglucose (2-DG) for 48 hours. We also used real-time polymerase chain reaction to obtain quantitative measurements of expression levels of Grp78, Grp94, CHOP, MTJ-1, HKII, MDR-1, MRP-1, HO-1, and Par-4. Cell number, viability, and proliferation of HepG2 cells were monitored with a real-time cell analyzer system (xCELLigence). We show that ouabain modulates the UPR transcription program and induces cell death in glucose-deprived tumor cells. Ouabain at all concentrations showed no cytotoxicity whereas all concentrations were very effective under 2-DG stress conditions. Our findings show that disruption of the UPR during glucose deprivation could be an attractive approach for selective cancer cell killing and could provide a chemical basis for developing UPR-targeting drugs against solid tumors. Ouabain use as an adjunct to conventional cancer therapy also warrants vigorous investigation. © Copyright 2012, Mary Ann Liebert, Inc. 2012.

OZET Telomer, kromozom uclarinda TTAGGG gibi, guaninden zengin kisa dizelerin ardisik tekrarlarindan ve buna bagli bazi proteinlerden olusan bir kompleksdir. Farkli turdeki canlilarda ve ayni turde farkli hucre ve dokularda farkli uzunluklara sahiptir. DNA replikasyonu esnasinda telomer 50-150 baz kadar kisalarak kromozomal stabilitenin korunmasina katkida bulunur. Telomerin yaslanma, kanser ve normal hucre biyolojisindeki onemini anlayabilmek icin yapilan calismalarda; telomer uzunlugu, altin standart olarak kabul edilen Southern Blot yaninda birkac farkli metodla olculmustur. Bu metodlarin kendine gore ustun ve eksik yonleri bulunmaktadir. Biz de bu calismada, ratlarin telomer uzunlugu olcumunde kullanabilecegimiz ve daha sonraki calismalara da uygulanabilir bir kantitatif PCR protokolu olusturmayi ve bu protokolle farkli rat dokularindaki telomer uzunluklari hakkinda bilgi edinmeyi amacladik. Dort erkek Sprague-Dawley cinsi ratin karaciger, ince bagirsak ve pankreas dokusu ve lenfositlerinden DNA izolasyonu yapildi. Numunelerde genom sayisini belirleyebilmek icin tek kopya gen olarak 36B4 geni secildi. 36B4 genine spesifik primerlerin kullanildigi Q-PCR ile bir rat dokusundaki genom kopya sayisi bulundu. Rat genom standardi olarak kullanilan bu numune tum numunelerdeki genom sayisini bulmak icin kullanildi. Tum numunelerde telomer (T) ve 36B4 (S) icin kantitatif PCR yapildi. Iki calismada ile elde edilen urunler birbirine oranlarak her numune icin T/S orani daha sonra da bir kalibrator numune kullanilarak relatif T/S orani hesaplandi. Ayrica 10,2 kb telomer standardi kullanarak numunelerin telomer uzunluklari kilobaz olarak da hesaplandi. Relatif kantitasyon icin mutlak gerekli olan Telomer ve 36B4 PCR calismalarinda % 100 verimlilige ulastik. Bunu logaritmik baslangic konsantrasyona karsi ΔCT grafigi slope degerinin 0,1’den kucuk olmasi ile de gosterdik. Ayrica telomer uzunlugu acisindan rat dokulari arasinda anlamli bir fark bulundu (p < 0,05). Sonuc olarak rat dokularinda telomer uzunlugu olcumu icin hassas, kolay ve hizli bir Q-PCR protokolu olusturdugumuzu dusunmekteyiz. The measurement of telomere length in sprague-dawley rats by quantitative PCR ABSTRACT Telomere consist of sequential repetitions of guanine-rich short sequences, such as TTAGGG, and some related proteins complexes in the ends of chromosomes. The dif¬ferent organisms and different cells and tissues of same organisms have different telom¬ere lengths. Telomere contributes to the protection of chromosomal stability by shorten ~50–150 base during DNA replication. Telomere length was measured by several differ¬ent methods as well as Southern blot, which is considered the gold standard in the studies to understand the importance of telomere in aging, cancer and normal cell biology. These methods has specific superior and limitations to himself. In this study, we aimed to create a quantitative PCR protocol, we can use to measurement of telomere length of rats and can also be applied in subsequent studies, and to obtain information about the telomere lengths in the different tissues of rats by this protocol. Genomic DNA was extracted from liver, small intestine, pancreas tissue and lymphocytes of four male Sprague-Dawley rat. The 36B4 gene was chosen as single copy gene for determine the number of genom in the samples. The number of genome copies were found in a rat tissue by qPCR that is used the 36B4 gene-specific primers. This sample, that is used as rat genom standarts, was used for find the number of genome in all samples. The qPCR was performed for telomere (T) and 36B4 (S) in all samples. The T / S ratio was calculated by the ratio of the products derived from two studies to each other, and then the relative T / S ratio was calculated by using a calibrator sample for each sample. In addition, telomere lengths of the samples were also calculated as kilobase by using 10,2 kb long telomere standard. We reached to 100% of efficiency in the studies of telomere and 36B4 PCR, it is necessary to the relative quantitation. We also demonstrated by the value of slope in ΔCt graphics versus logaritmic initial concentration is less than 0,1. In addition, a statistically any significant difference found between tissues of rat for telomere length (p

The aim of this experimental study was to investigate the penetration of methotrexate into the brain parenchyma after indirect nonanastomotic by-pass surgery (encephalo-myo-synangiosis) in rats. The fourteen rats were divided into two groups as control and operated rats. Control rats were not operated but received methotrexate treatment (50 mg/kg). The operation of indirect nonanastomotic by-pass was done on operated group. After four weeks from the operation, methotrexate (50 mg/kg) was injected via intravenous route one hour before the decapitation. Parenchymal methotrexate level was estimated by using biochemical methods. The mean methotrexate level in the brain parenchyma of control group was estimated as 1.16± 0.93 µmol/L. The mean methotrexate level in the brain parenchyma of operated group was found as 2.5±0.98 µmol/L. The operation of pial synangiosis enhanced the penetration of methodrexate into the brain parenchyma in comparison with unoperated subjects. The differences between these two groups were statistically meaningful (p=0.0221). In this experimental study, we used the operation of encephalo-myo-synangiosis (EMS) for enhancing of the penetration of methotrexate into the brain. According to our results the operation of EMS enhanced the penetration of methotrexate into the brain parenchyma in the rats.

BAYDIN, AHMET/0000-0003-4987-0878; Bozkurt, Ayhan/0000-0002-5794-709X; Bilge, S.Sirri/0000-0003-2878-6968 WOS: 000286679100004 PubMed: 20375122 Acute carbon monoxide (CO) poisoning can cause early and persistent damages in tissues sensitive to hypoxia. This study investigated serum heart-type fatty acid-binding protein (H-FABP) levels as a biomarker of acute CO poisoning in rats. The rats were exposed to a mixture of either 3000 (group A) or 5000 (group B) parts per million (ppm) CO in air, or to ambient air (group C, control group). Blood samples were taken just before, immediately after and 6 hours after the exposure, and serum H-FABP and troponin-I levels were measured. The consciousness level was evaluated just after the exposure. The survival rate was monitored for 7 days. Serum H-FABP levels increased just after the CO exposure in both groups A and B. Additionally, H-FABP level was higher in group B than in group A, immediately after the exposure. However, serum troponin-I levels only increased at 6 hours after the CO exposure in groups A and B. Consciousness and survival rates in group B were lower than that in group A. Our results suggest that H-FABP might have potential to be an early and quantitative parameter of clinical severity and prognosis in CO poisoning.

ozkaya, ozan/0000-0002-0198-1221 WOS: 000276364200013 PubMed: 20370454 Aim: Nephrotoxicity is a major side effect of cisplatin (Cis), a widely used chemotherapeutic drug. Recent studies have strongly suggested that inflammatory mechanisms may play an important role in the pathogenesis of Cis nephrotoxicity. Rosiglitazone (Ros), a peroxisome proliferator-activated receptor-gamma agonist has been recently demonstrated to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The aim of this study was to evaluate the effect of Ros on the prevention of Cis-induced nephrotoxicity. Methods: Eighteen male Sprague-Dawley rats weighing 150-200 g were included in the study. The rats were randomly divided into three groups: group 1: Cis-treated group; group 2: Cis-Ros-treated group; group 3: saline-treated group. Blood urea nitrogen (BUN) and serum creatinine concentrations were measured. In addition, extent of histological renal tubular injury in each animal was graded histologically. Results: Mean BUN and serum creatinine concentrations were significantly lower in group 3 than in group 1 (p < 0.05) and group 2 (p < 0.05). There were no significant differences in terms of BUN and serum creatinine concentrations between groups 1 and 2 (p > 0.05). Acute tubular injury with karyomegalic changes in corticomedullary junction was significantly higher in groups 1 and 2 than group 3 (p < 0.05). However, there were no significant differences between groups 1 and 2 (p > 0.05). Conclusion: This study indicates that post-insult administration of Ros does not seem to have a beneficial effect on prevention and severity of nephrotoxicity induced by Cis.

WOS: 000273448200009 PubMed: 19888587 In this study, we have examined the correlation between colorectal cancer (CRC) and serum adiponectin and resistin levels, body mass index and insulin resistance. The relation between serum adiponectin and resistin levels, obesity and insulin resistance in 36 CRC patients and 37 controls was examined. Insulin and homeostasis model assessment insulin resistance index (HOMA-IR) levels were higher, and adiponectin levels were significantly decreased in patients versus controls, whereas, resistin levels were significantly increased. A negative correlation between adiponectin, HOMA-IR, and insulin and a positive correlation between HOMA-IR, insulin, and stage were detected. There was no correlation between the stage and resistin. Adiponectin level negatively correlated with the stage. Adiponectin and resistin could play a role in colon cancer carcinogenesis, and adiponectin could be responsible for poor prognosis in colorectal cancer.

BEK, KENAN/0000-0002-1005-2379; ozkaya, ozan/0000-0002-0198-1221 WOS: 000269789100003 PubMed: 19684410 Background/Aims: Plasma levels of cell-free DNA (cfDNA) are elevated in various clinical conditions including cancer, stroke, trauma, myocardial infarction, autoimmune disorders, and pregnancy-associated complications. Previously, increased cfDNA levels were reported during hemodialysis. However, there is limited data regarding cfDNA levels in peritoneal dialysis (PD) patients. The aim of this study was to investigate the levels of cfDNA in children on PD. Methods: Twenty-one children on PD (median age: 12; range: 4-18 years) and 21 healthy children (median age: 10; range: 6-16 years) were enrolled into the study. Plasma cfDNA was measured using a real-time quantitative PCR for the beta-globin gene. Results: The median concentrations of cfDNA in the plasma of PD patients and healthy controls were 2,205 genome-equivalents/ml of plasma (range: 39-5,845) and 1,033 genome-equivalents/ml of plasma (range: 254-5,116), respectively (p = 0.026). A significant positive correlation was observed between C-reactive protein levels and plasma cfDNA levels (r: 0.52, p < 0.0001). Conclusion: Our data have demonstrated for the first time that cfDNA is increased in children on PD treatment. However, the mechanism by which the levels of cfDNA is increased and the clinical significance of this finding in PD patients is unclear. Further studies are warranted to clarify the precise mechanism and clinical significance of elevated cfDNA in children on PD. Copyright (C) 2009 S. Karger AG, Basel Research Fund of Ondokuz Mayis UniversityOndokuz Mayis University [T-411] This study was supported by the Research Fund of Ondokuz Mayis University (Grant Number: T-411).

WOS: 000254477800003 PubMed: 18213655 Pioglitazone (PIO), a member of the thiazolidinedione class of antidiabetic agents, specifically targets insulin resistance. Drugs of this class act as ligands for the gamma subtype of the peroxisome proliferator-activated receptor. Although troglitazone, another drug in this class, displayed unacceptable hepatotoxicity, PIO was approved for human use by the U.S. Food and Drug Administration. To our knowledge, there are no published reports on the genotoxicity of PIO; however, the package insert indicates that it has minimal genotoxicity. In this study, we used the comet assay to investigate the DNA damage in the peripheral blood and liver cells of rats treated with PIO. Sixteen male Sprague-Dawley rats were randomly distributed into four groups, and dosed daily for 14 days by oral gavage with 0, 10, 20, and 40 mg/kg/day PIO. A dose-dependent increase in DNA damage, as assessed by % tail DNA, was observed in both hepatocytes and blood lymphocytes of the PIO-treated groups, with significant increases detected between the rats treated with all the doses of PIO and the control, and between the rats treated with different PIO doses (P < 0.005 to P < 0.0001). Treating nuclei from the exposed animals with an enzyme cocktail containing Fpg and Endonuclease III prior to performing the comet assay increased the level of DNA damage, which reflects oxidized purine and pyrimidine. Taken together, our data indicate that PIO is able to dose-dependently induce DNA damage in both the liver and blood lymphocytes of rats, which is partially due to the generation of oxidative lesions.

BEK, KENAN/0000-0002-1005-2379; ozkaya, ozan/0000-0002-0198-1221 WOS: 000240555500015 PubMed: 16937131 Selenium (Se) is a trace element that incorporates into the selenoenzyme glutathione peroxidase (GSH-Px). There are conflicting results regarding the Se levels and activity of GSH-Px in adult uremic patients. The aim of this study was to determine (1) the hair Se status, (2) the possible relation between the hair Se status and the antioxidant enzyme, GSH-Px, and (3) the influence of different treatment procedures on hair Se status and GSH-Px activity in children with CRI, those treated conservatively and those on HD and on CAPD. Ninety-three patients, including 32 patients with CRI, treated conservatively, 42 PD patients, 19 HD patients and 34 healthy children were enrolled in the study. The hair Se level was measured by the atomic absorption spectrophotometer method. Plasma GSH-Px activity was determined using a Randox test combination (RANSEL). Hair Se levels were significantly lower in the CRI, CAPD, and HD groups when compared to the control group (P=0.001, P=0.001, and P=0.001, respectively). Plasma GSH-Px activity was significantly lower in the CRI, CAPD, and HD groups when compared to the control group (P=0.001, P=0.001, and P=0.001, respectively). Plasma GSH-Px activity correlated with the GFR in patients with CRI and the control group (P=0.000; r(2)=0.60). There was no correlation between plasma GSH-Px and hair Se levels in the patient and control groups. These results revealed a decreased hair Se level and impaired antioxidative capacity in children with CRI on CAPD and HD. The lack of any relation between plasma GSH-Px and hair Se suggests that plasma GSH-Px is not a good marker of Se stores.

WOS: A1997XZ66300009 PubMed: 9334867 A possible agent for human non-A-E hepatitis has been identified and named hepatitis G virus (HGV). The aim of this study is to evaluate the prevalence of serum HGV-RNA among hemodialysis patients in our country and the possible correlations of serum HGV-RNA,vith antibody to hepatitis C virus (anti-HCV), chronic liver dysfunction, number of blood transfusions, serum hepatitis B surface antigen (HBs Ag), duration of hemodialysis therapy, history of renal transplantation and patients' age and sex, Seventy-eight hemodialysis patients and 59 healthy controls were included in the study. Twenty-seven of 78 hemodialysis patients (34.6%) and two of the 59 healthy controls were serum HGV-RNA positive (p < 0.01, x(2) = 17.8), There was no significant difference between the HGV-RNA positive and HGV-RNA negative groups regarding mean duration of dialysis therapy, anti-HCV, chronic liver dysfunction, number of blood transfusions, serum HBs Ag, duration of hemodialysis therapy history of renal transplantation and patients' age and sea. In conclusion, hemodialysis patients carry the risk for HGV infection and transmission routes and clinical significance of HGV infection in these patients remain to be defined.

WOS: 000221819700004 PubMed: 15189171 Background: Thromboembolic events are seen more frequently in patients with chronic renal failure (CRF) and amyloidosis. The anticardiolipin antibody (ACA) that is important for thromboembolic events has never been studied. Methods: This study included 43 amyloidosis patients of different aetiologies; 28 with CRF as well as 20 patients who had CRF without amyloidosis. Thirty normal subjects were included as a control group. We determined the serum levels of ACA, apolipoprotein AI (ApoAl), ApoE and lipoprotein (a) (Lp(a)) in these groups. Results: Anticardiolipin antibody was found to be positive in 30.2% of patients with amyloidosis, this is in contrast to 3.3% in the control group (chi = 8.25, P < 0.005). We also showed that there was a statistically significant difference (chi = 5.03, P < 0.05) between the CRF patients with amyloidosis (31%) and the CRF patients without amyloidosis (5%). The average levels of serum ApoAI were shown to be significantly lower (P < 0.05) in CRF patients with amyloidosis in comparison with the amyloidosis patients who had normal renal functions (93.60 +/- 27.84 vs 119.8 +/- 36.26 mg/dL, P < 0.05). There was also significant a difference in ApoAI levels between CRF patients with and without amyloidosis (P < 0.001). The serum Lp (a) levels were significantly higher in CRF patients with amyloidosis when compared with the controls (41.2 +/- 22.39 vs 19.13 +/- 8.78 mg/dL, P < 0.001). The serum Lp (a) levels were also positively correlated with ACA (r = 0.211; P < 0.05). Conclusion: In conclusion, ACA positivity is more common in all patients with amyloidosis as compared with CRF patients and normal controls. This study is the first to show the presence of high levels of ACA in patients with CRF, which is caused by secondary amyloidosis. Further studies are recommended to investigate the mechanism of this finding.

WOS: 000185416500008 PubMed: 12883976 Amyloidosis (A) related to familial Mediterranean fever (FMF) causes serious morbidity and mortality in children. Our study evaluates serum levels of apolipoprotein (Apo) AI, AII, B, and E and Apo AII/AI ratios as a non-invasive diagnostic tool for amyloidosis in children with FMF and FMF-A. Results were compared with those of patients with childhood nephrotic syndrome (NS) and healthy children (controls). Significantly lower serum levels of Apo AI (90.20+/-28.30 mg/dl) were documented in patients with FMF-A than in all other groups (FMF 126.89+/-51.07 mg/dl, NS 140.38+/-33.73 mg/dl, and controls 134.67+/-12.73 mg/dl) (P0.05). It is concluded that a decreased Apo AI serum level, but not Apo AII/AI ratio, is a useful, non-invasive test for the early diagnosis of FMF-A in children.