Nuray Yazihan

Cancer Trends and Incidence and Mortality Patterns in Turkey

Cancer incidence and mortality rates have been increasing in Turkey as most of the developing countries. Besides socioeconomic factors, one of the most prominent attributes of developing countries is the dissimilarity of their age-dependent demographic structure. In Turkey, cancer incidence rates rise due to individual and environmental risk factors as well as due to the improvement in the registry system and to increase in access to health services. According to the data retrieved from the Ministry of Health Department of Cancer Control database cancer incidence rates increased between 2002 and 2005. Incidence rates rose from 133.78 per 100 thousand in 2002 to 173.85 per 100 thousand in 2005. Between 2002 and 2005 the average growth rate of increase for men comes about 9.7%, which is higher than 8.6% for women leading to the widening of incidence gap between man and women. First five frequent cancer types in Turkey are lung (30.13), prostate (24.33), skin (18.91), breast (17.96), stomach (9.92) cancer with an incidence of per 100 thousand. Cancer incidence growth rates for men exceed the cancer incidence growth rate for women. This gap is resulting mainly from lung cancer incidence which is much higher for men. Further extension of the nationwide cancer screening and prevention programs will result in improvement of cancer control.

Erythropoietin improves oxidative stress following spinal cord trauma in rats

Spinal cord injury (SCI) is a very destructive process for both patients and society. Lipid peroxidation is the main cause of the further secondary damage which starts after mechanical destruction of tissues. Recent studies have shown that erythropoietin (EPO) has neuroprotective properties. In this study, we aimed to see the effect of EPO treatment after spinal cord injury on the oxidant and anti-oxidant enzyme systems and the relationship with the N-methyl-D-Aspartate (NMDA) blockage. Spinal cord injury was produced by epidural compression with a cerebral vascular clip that has a closing force of 40 g for 30s after a limited multilevel laminectomy (T9-11). Experiment was done in 5 groups: Group 1: Sham-operated untraumatised, Group 2: SCI untreated, Group 3: 150 i.u./kg EPO injected i.p. at the end of the first hour following the trauma. Group 4: NMDA receptor antagonist ketamine (100mg/kg) i.p. Group 5: EPO+ketamine i.p. The experiments were finished after 12h of the trauma. The spinal cords were excised for biochemical examinations. Anti-oxidant enzymes; catalase and reduced glutathione (GSH) levels increased and lipid peroxidation product, malonyldialdehyde (MDA) level decreased in EPO treated group when compared to the other groups. TNF-alpha levels decreased in EPO treated group. Application of ketamine before EPO treatment decreased effects of EPO. In conclusion, our results suggest that 150 i.u./kg i.p. EPO, a therapeutic dose in anaemic patients, applied after 1h of spinal cord injury significantly attenuated the oxidative damage of spinal cord injuries in rats. This activity is abolished via ketamine pretreatment.

The effect of intracerebroventricular injection of beta amyloid peptide (1-42) on caspase-3 activity, lipid peroxidation, nitric oxide and NOS expression in young adult and aged rat brain.

AIM Intracerebroventricular (icv) administration of beta amyloid peptide (Aβ) in rats can be used to model certain aspects of Alzheimer disease (AD).The purpose of this study was to examine the effects of intracerebroventricular Aβ (1-42) peptide injection on caspase-3 activity and expression of nNOS and iNOS, malondialdehyde (MDA), glutathione (GSH) and NOx in the hippocampus, temporal cortex and parietal cortex. MATERIAL AND METHODS Groups were defined as 1) young adult control, 2) Aβ (1-42) injected young adult, 3) aged control and 4) Aβ (1-42) injected aged group. Stereotaxic surgery was performed. Aβ (1-42) peptide (5μg/1μl, in each icv) was administered bilateral intracerebroventricularly as a single injection. RESULTS Caspase-3 activity significantly increased in Aβ (1-42) injected aged rats when compared with young adult rats. Aβ (1-42) significantly increased lipid peroxidation in both young adult and aged rats. There was an increase in nNOS expression in the temporal cortex of Aβ (1-42) injected aged rats. CONCLUSION The most significant increase was seen in hippocampus in caspase-3 levels of the Aged- Aβ 1-42 group. nNOS expression in the hippocampus of aged rats was increased compared to young adult rats. However, nNOX expression in the hippocampus of Aβ (1-42) injected aged rats decreased significantly.

Erythropoietin reduces lipopolysaccharide-induced cell Damage and midkine secretion in U937 human histiocytic lymphoma cells

IntroductionErythropoietin (EPO) is a haematopoietic stimulatory protein that is used to treat anaemia in patients on dialysis. In addition, EPO has been shown to have anti-inflammatory properties, which may be important as dialysis patients tend to exist within a chronic, low-grade inflammatory state, and tend to be more susceptible to infections. It has been suggested that EPO has direct immunomodulatory potency on monocytes/macrophages.MethodsIn this study, we aimed to clarify the effects of EPO during the inflammatory processes in human mononuclear phagocytic cells by monitoring the secretion of the following cytokines; midkine, tumour necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). For this purpose, U937 human histiocytic lymphoma cell lines were used. Time-dependent effects of varying doses of EPO (0.1 to 50 IU/ml) treatment during lipopolysaccharide (LPS)-mediated cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide test. LPS-stimulated midkine secretion was measured immunohistochemically and quantification of TNF-α, IL-6 and midkine secretion was achieved by ELISA.ResultsEPO treatment prevented the direct toxic effects of LPS on the U937 cells. TNF-α, IL-6 and midkine secretions were found to increase in the U937 cells in response to LPS treatment. Interleukin-6 response was varied in a doseand time-dependent manner.ConclusionTreatment with EPO significantly inhibits the LPS-induced secretion of midkine and TNF-α regardless of the dosage. The data presented here provide the first evidence to indicate that EPO treatment directly reverses some of the cytotoxic and secretory effects of LPS in mononuclear cells. Inhibition of midkine secretion might be responsible for the anti-inflammatory role of EPO.

Effect of leptin on renal ischemia-reperfusion damage in rats

Tumor necrosis factor-alfa (TNF-α) has been established as an important mediator in renal ischemia-reperfusion (I/R) injury. Leptin, a product of the ob gene, has been known to exhibit cytoprotective effects on renal tissue, but its effect on renal tissue TNF-α level after renal I/R injury in rats remains unknown. The purpose of the study was to evaluate the effects of leptin on renal tissue TNF-α, malondialdehyde (MDA), protein carbonyls (PCs) and total sulfydryl group (SH) levels, and plasma nitrite levels after renal I/R injury in rats. The animals were divided into three groups: control, I/R and I/R+leptin. Rats were subjected to renal ischemia by clamping the left pedicle for 45 min, and then reperfused for 1 h. The I/R+leptin group was pretreated intraperitoneally with leptin (10 μg/kg) 30 min before the induction of ischemia. Our results indicate that MDA, TNF-α levels, and PCs were significantly higher in the I/R group than those in the control group (p<0.05). The administration of leptin decreased these parameters (p<0.05) significantly. The SH level was observed to significantly decrease after I/R injury when compared to the control group (p<0.05). Leptin treatment significantly increased tissue SH and plasma nitrite levels when compared to the I/R group (p<0.05). Plasma nitrite levels did not change significantly in I/R when compared to the control. These results suggest that leptin could exert a protective effect on I/R induced renal damage by decreasing TNF-α levels and increasing nitrite level.ResumenEl factor de necrosis tumoral alfa (TNF-α) está implicado en la lesión renal tras isquemia y reperfusión (I/R). Dado que se ha observado que la leptina presenta un efecto citoprotector sobre el tejido renal, se estudia en este trabajo el efecto de la hormona sobre el contenido en el tejido renal de TNF-α, malondialdehido (MDA), niveles de grupos carbonilo protéicos (PC) y de los grupos sulfhidrilo total (SH), y el nivel plasmático de nitrito tras lesión renal por isquemia/reperfusión en rata. Los animales se repartían en tres grupos de 8 ejemplares: control, I/R, e I/R+leptina. Las ratas se sometían a una isquemia renal durante 45 minutos con ulterior reperfusión de una hora. A los del grupo I/R+leptina se les había administrado por vía intraperitoneal leptina (10 μg/kg) 30 minutos antes de la inducción de la isquemia. Los resultados indican que el contenido en MDA, TNF-α y PC está significativamente elevado en el grupo I/R respecto del grupo de control (p<0.05), mientras que el de SH se reduce tras la lesión I/R y el nivel de nitrito en el plasma no varía. El tratamiento con leptina anula los incrementos de los niveles renales de TNF-α, MDA y PC y de la disminución de grupos SH en tejido renal e incrementa el nivel de nitritos plasmáticos por isquemia/reperfusión renal. Estos resultados sugieren que la leptina ejerce un efecto protector sobre la lesión renal inducida por isquemia y reperfusión por la disminución de TNF-α y el aumento plasmático de nitrito.

Nerium oleander Distillate Improves Fat and Glucose Metabolism in High-Fat Diet-Fed Streptozotocin-Induced Diabetic Rats

Diabetes was induced by intraperitoneal injection of streptozotocin (35 mg/kg bw) in all rats of five groups after being fed for 2 weeks high-fat diet. Type 2 diabetic Nerium-oleander- (NO-) administered groups received the NO distillate at a dose of 3.75, 37.5, and 375 μg/0.5 mL of distilled water (NO-0.1, NO-1, NO-10, resp.); positive control group had 0.6 mg glibenclamide/kg bw/d by gavage daily for 12 weeks. Type 2 diabetic negative control group had no treatment. NO distillate administration reduced fasting blood glucose, HbA1c, insulin resistance, total cholesterol, low density lipoprotein, atherogenic index, triglyceride-HDL ratio, insulin, and leptin levels. Improved beta cell function and HDL concentration were observed by NO usage. HDL percentage in total cholesterol of all NO groups was similar to healthy control. NO-10 distillate enhanced mRNA expressions of peroxisome proliferator-activated-receptor- (PPAR-) α, β, and γ in adipose tissue and PPAR-α–γ in liver. The findings from both in vivo and in vitro studies suggest that the considerable beneficial effect of NO distillate administration at a dose of 375 μg/0.5 mL of distilled water may offer new approaches to treatment strategies that target both fat and glucose metabolism in type 2 diabetes.

Association between plasma asymmetrical dimethylarginine activity and severity of aortic valve stenosis

Objectives Aortic valve stenosis is the most common valvular heart disease in the Western world. The most common cause of aortic valve stenosis in adults is calcification of a normal trileaflet or congenital bicuspid valve. Calcific aortic valve stenosis is an active disease process characterized by mechanical stress, endothelial damage, lipid accumulation, inflammation, synthesis of extracellular matrix proteins, and calcification, reminiscent of atherosclerosis in many aspects. Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase which reduces the bioavailability of nitric oxide and begets endothelial dysfunction. The goal of this study was to examine the association between ADMA activity and severity of aortic valve stenosis. Methods One hundred and nine patients were included in this study. Patients were grouped as those with mild aortic stenosis (42 patients, group 1), moderate aortic stenosis (36 patients, group 2), and severe aortic stenosis (31 patients, group 3). ADMA activity was measured by ELISA kit. Results Mean ADMA activity in group 3 was significantly higher than that in groups 1 and 2 (1.94 ± 0.45 vs. 0.87 ± 0.37 μmol/l, P < 0.001 and 1.94 ± 0.45 vs. 1.34 ± 0.52 μmol/l, P < 0.001, respectively). Serum ADMA activity was positively correlated with mean aortic gradient and maximum aortic gradient and negatively correlated with aortic valve area. Conclusion Our results showed that serum ADMA activity is higher in patients with severe aortic valve stenosis. ADMA activity is positively correlated with aortic valve stenosis severity. Serum ADMA level may be used as a precious marker to evaluate and follow up the severity of aortic valve stenosis.

Decreased therapeutic effects of noscapine combined with imatinib mesylate on human glioblastoma in vitro and the effect of midkine

BackgroundGlioblastoma (GBM) develops resistance to the advances in chemotherapy leading to poor prognosis and life quality. Consequently, new treatment modalities are needed. Our aims were to investigate the effects of combined noscapine (NOS) and imatinib mesylate (IM) on human GBM in vitro and the role of midkine (MK) in this new combination treatment.MethodsMonolayer and spheroid cultures of T98G human GBM cell line were used to evaluate the effects of IM (10 μM), Nos (10 μM) and their combination on cell proliferation and apoptotic indexes, cell cycle, the levels of antiapoptotic MK, MRP-1, p170, PFGFR-α, EGFR, bcl-2 proteins, apoptotic caspase-3 levels, morphology (SEM) and ultrastructure (TEM) for 72 hrs. Results were statistically analyzed using the Students t-test.ResultsThe combination group induced highest decrease in cell proliferation and apoptotic indexes, caspase-3 levels, MRP-1 and PDGFR-α levels. The decrease in p170 levels were lower than IM but higher that NOS. The highest increases were in EGFR, MK, bcl-2 and cAMP levels in the combination group. The G0+G1 cell cycle arrest at the end of 72nd hr was the lowest in the combination group. Apoptotic appearence was observed rarely both in the morphologic and ultrastructural evaluation of the combination group. In addition, autophagic vacuoles which were frequently observed in the IM group were observed rarely.ConclusionsThe combination of Nos with IM showed antagonist effect in T98G human GBM cells in vitro. This antagonist effect was correlated highly with MK levels. The effects of NOS on MRP-1, MK and receptor tyrosine kinase levels were firstly demonstrated in our report. In addition, we proposed that MK is one of the modulator in the switch of autophagy to cell death or survival/resistance.

Relationship of paraoxonase-1, malondialdehyde and mean platelet volume with markers of atherosclerosis in familial Mediterranean fever: an observational study.

OBJECTIVE There are many studies demonstrating deteriorated ventricle and endothelium functions in familial Mediterranean fever (FMF) patients. As FMF is an autoinflammatory disease with an ongoing inflammatory activity and inflammation plays an important role in the development and progression of atherosclerosis in some of the rheumatic diseases, we aimed to investigate the early markers of atherosclerosis in patients with FMF by the measurements of serum paraoxonase-1 (PON-1) activity, mean platelet volume (MPV) and malondialdehyde (MDA) level. METHODS This study is a cross-sectional, observational study. Forty consecutive patients with FMF and twenty healthy volunteers were selected to form the study population. The diagnosis of FMF was based on Tel-Hashomer criteria. Serum PON-1 activity, MPV and MDA level were determined to examine their association with FMF. Students t-test, Mann-Whitney U test, Pearson correlation analysis were used for statistical analysis. RESULTS The mean PON-1 activity in FMF patients was significantly lower than in the healthy population (141.46±38.29 vs. 179.62±10.73 U/l, p<0.01). Serum MDA levels were the same between the groups (1.08±0.66 vs. 1.08±0.33 nmol/mL, p=0.99). MPV was higher in FMF patients than in the control l group (8.87±0.99 vs. 8.22±0.45 fl, p=0.04). PON, MPV and MDA levels were the same in FMF patients with acute attack and attack -free period. CONCLUSION Our results show that PON-1 activity is lower in patients with FMF. Reduced PON-1 activity and increased MPV, independent of the oxidative stress status of these patients, may lead to increased atherosclerotic propensity in FMF.

Impaired right ventricular functions in metabolic syndrome patients with preserved left ventricular ejection fraction.

OBJECTIVES Metabolic syndrome (MetS) has been shown to be independently associated with increased risk for incident heart failure and coronary artery disease. We investigated whether there was deterioration in right ventricular functions in MetS patients with preserved left ventricular functions and its association with the number of MetS components. STUDY DESIGN The study included 192 consecutive patients (148 women, 44 men; mean age 54.3 ± 8.5 years) with the diagnosis of MetS based on the NCEP-ATP III criteria and 20 healthy controls (12 women, 8 men; mean age 51.6 ± 8.4 years). All subjects underwent conventional and tissue Doppler (TDI) echocardiography to assess left and right ventricular functions, including right ventricular myocardial performance index (MPI) and tricuspid annular plane systolic excursion (TAPSE). RESULTS The number of MetS components were three in 43.8%, four in 31.3%, and five in 25% of the patients. Right ventricular TDI-derived MPI was higher in patients with MetS compared to controls [median 0.5 (range 0.2-3.3) vs. 0.3 (0.1-0.7), p=0.000]. This was possibly due to significantly shortened right ventricular ejection time in MetS patients (p<0.05). Although TAPSE was within the normal range in MetS patients, it was significantly decreased compared to controls (p=0.000), accompanied by significantly lower TDI-derived S wave, E wave, and E/A ratio (p=0.000). None of the MetS components were significantly correlated with right ventricular TDI-derived MPI. There was no association between the number of MetS components and echocardiographic parameters. CONCLUSION Our findings show that, despite preserved left ventricular systolic functions, both systolic and diastolic functions of the right ventricle deteriorate in MetS patients.