Dilara Kaman

A preliminary study of human paraoxonase and PON 1 L/M55-PON 1 Q/R 192 polymorphisms in Turkish patients with coronary artery disease.

Paraoxonase 1 (PON 1) is a high‐density lipoprotein (HDL)‐associated enzyme with antioxidant function protecting low‐density lipoprotein (LDL) from oxidation. PON 1 has two amino acid polymorphisms in coding region; L/M 55 and Q/R 192. These polymorphisms modulate paraoxonase activity of the enzyme. PON 1 activity decreases in coronary artery disease (CAD). In the present study, distribution of PON 1 L/M 55 and Q/R 192 polymorphisms and the effect of these polymorphisms on the activities of PON 1, and on the severity of CAD in 277 CAD (+) patient and 92 CAD (−) subjects were examined. PON 1 L/M 55 and Q/R 192 genotypes were determined by PCR, RFLP and agarose gel electrophoresis techniques. Genotype distributions and allele frequencies for PON 1 Q/R 192 polymorphism were not significantly different between controls and CAD (+) patient group (p > 0.05), but in genotype and allele distribution of PON 1 L/M55 polymorphism, there was significantly difference among groups (p < 0.05). Genotype distributions for both polymorphisms were not significantly different between subgroups of single‐vessel disease (SVD), double‐vessel disease (DVD) and triple‐vessel disease (TVD). Serum PON 1 activity was lower in CAD (+) group than in controls and this was also statistically significant (p < 0.001). In both groups, the highest PON activities were detected in LL and RR genotypes. In summary, our results suggest that there is an association between the PON 1 L/M 55 polymorphism of paraoxonase and CAD in Turkish patients but not with PON 1 Q/R 192 polymorphism. However, it is hard to correlate these polymorphisms and severity of CAD. Copyright

Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and plasma concentrations of asymmetric dimethylarginine in Turkish pre-eclamptic women without fetal growth retardation

Aims:  Pre‐eclampsia (PE) is a leading cause of maternal death worldwide, affecting 3 to 5% of all pregnancies. We analyzed the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and asymmetric dimethylarginine (ADMA) in 55 Turkish patients with PE without fetal growth retardation (FGR) and in 54 healthy pregnant women.

Effects of coenzyme Q10 and α-lipoic acid supplementation in fructose fed rats

This study was conducted to investigate the effects of α-lipoic acid and coenzyme Q10 on plasma levels of lipids, asymmetric dimethylarginine, oxidative stress in fructose fed rats which provide a model of dietary-induced insulin resistance and to evaluate vascular changes developing in these rats by histologically. Male Sprague Dawley rats were used in this study. The animals were divided into 4 groups. Group 1 did not receive any medication and served as a control. Group 2 received a regular diet and water ad libitum and fructose was administered as % 10 solution in drinking water. Group 3 received α-lipoic acid (100 mg/kg/day) i.p. for 5 weeks and Group 4 received coenzyme Q10 (10 mg/kg/day) i.p. for 5 weeks. For determination of plasma asymmetric dimethylarginine, glutathione and malondialdehyde levels, high-performance liquid chromatography system was used. Homeostatic model assessment as a measure of insulin resistance was calculated. Lipid profile measurements were determined using enzymatic assay on an Auto analyzer. The high fructose diet was significantly associated with an increase in levels of plasma LDL, VLDL and total cholesterol and decrease in level of HDL cholesterol. Plasma asymmetric dimethylarginine, malondialdehyde and glutathione levels were also increase in these rats. α-lipoic acid or coenzyme Q10 supplementation was found to have some positive effect on these parameters. These findings were also demonstrated by morphological observation of the aorta. We demonstrated that administration of α-lipoic acid and coenzyme Q10 notably suppresses oxidative and nitrative stress, hyperinsulinemia, insulin resistance developing in fructose fed rats, a model of metabolic syndrome (MS). These positive effects of α-lipoic acid or coenzyme Q10 can be attributed to its antioxidant activity.

Plasma osteopontin levels in patients with Behcet's disease and psoriasis

BACKGROUND Behcets disease (BD) is a chronic and recurrent systemic vasculitis marked by macrophage chemotaxis. OBJECTIVE The present study aimed to examine the relationship between the osteopontin molecule and BD. PATIENTS AND METHODS The study registered 60 patients with BD, as well as 50 healthy individuals and 63 patients with psoriasis as the control group. Patients with BD in our study were divided into 2 groups, with regard to mucocutaneous involvement, as active and inactive patients. In addition, patients with BD were also divided into 3 groups with regard to vascular involvement: active, inactive, and no vascular involvement. RESULTS Plasma osteopontin (OPN) levels in active patients with BD, inactive patients with BD and patients with psoriasis were found statistically significantly elevated, in comparison to those in the healthy control group (p < 0.001, p = 0.008, p < 0.001, respectively). When active and inactive patients with BD were compared to the healthy control group with regard to vascular involvement, mean plasma OPN levels were found to be statistically significantly higher (p = 0.01, p < 0.001, respectively). CONCLUSIONS We found that plasma levels of OPN were higher in patients with Behcets and psoriasis.

TaqIB and severity of coronary artery disease in the Turkish population: a pilot study

The cholesteryl ester transfer protein (CETP) plays a crucial role in high-density lipoprotein (HDL) metabolism. Genetic variants that alter CETP concentration may cause significant alterations in HDL-cholesterol (HDL-C) concentration. In this case-control study, we analyzed the genotype frequencies of CETP Taq1B polymorphisms in coronary artery disease patients (CAD; n=210) and controls (n=100). We analyzed the role of the CETP Taq1B variant in severity of CAD, and its association with plasma lipids and CETP concentration. DNA was extracted from 310 patients undergoing coronary angiography. The Taq1B polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (RFLP) analysis. Lipid concentrations were measured by an auto analyzer and CETP level by a commercial enzyme-linked immunosorbent assay (ELISA) kit. In our study population, the B2 allele frequency was higher in control subjects than patients with single, double or triple vessel disease. B2B2 genotype carriers had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than those with the B1B1 genotype in controls (51.93±9.47versus 45.34±9.93; p<0.05) and in CAD patients (45.52±10.81 versus 40.38±9.12; p<0.05). B2B2 genotype carriers had a significantly lower CETP concentration than those with the B1B1 genotype in controls (1.39±0.58 versus 1.88±0.83; p< 0.05) and in CAD patients (2.04±1.39versus 2.81±1.68; p< 0.05). Our data suggest that the B2 allele is associated with higher concentrations of HDL-C and lower concentrations of CETP, which confer a protective effect on coronary artery disease.

Assessment of heat shock proteins and endothelial dysfunction in acute pulmonary embolism.

We determined the levels of some heat shock proteins (HSP27, HSP70, and HSP90), L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) levels in patients with acute pulmonary embolism. The present case–control study comprised a healthy control group (n = 57) and patients with acute pulmonary embolism (n = 84). HSPs, L-arginine, ADMA, and SDMA levels were measured in all of the cases. The mean age of the control group was 56.72 ± 8.44 years, and the mean age of the patients with acute pulmonary embolism was 60.20 ± 16.56 years (P = 0.104). Compared with controls, patients with acute pulmonary embolism had significantly higher mean serum HSP27, HSP90, and ADMA levels, whereas the mean serum L-arginine and SDMA levels were lower (P < 0.001, for all parameters). In patients with acute pulmonary embolism serum HSP27, HSP70, and ADMA levels were negatively correlated with partial pressures of arterial oxygen levels (r = −0.281, P = 0.01; r = −0.263, P = 0.016; and r = −0.275, P = 0.011, respectively) and arterial oxygen saturation (r = −0.225, P = 0.039; r = −0.400, P < 0.001; r = −0.299, P = 0.006, respectively). The findings of the present study demonstrated that oxidative stress and endothelial damage increase in acute pulmonary embolism.

eNOS Glu298Asp Polymorphism and Endothelial Dysfunction in Patients with and without End-stage Renal Disease

BACKGROUND Chronic kidney diseases are known to influence nitric oxide metabolites (NOx) and asymmetric dimethylarginine (ADMA), though the exact mechanism is still poorly understood. AIMS The purpose of the present study was to examine eNOS Glu298Asp gene polymorphism, plasma NOx and ADMA concentration in subjects with and without End-stage Renal Disease. STUDY DESIGN Case-control study. METHODS In this study, genotype distributions of Glu-298Asp in exon 7 of the eNOS gene polymorphisms in 130 hemodialysis and 64 peritoneal dialysis patients were compared with 92 controls. NOx was measured by using the Griess reaction while arginine, ADMA and SDMA measurements were performed by HPLC. Genotyping for eNOS Glu298Asp polymorphism was detected with the polymerase chain reaction and/or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS When the genotype frequencies of TT and GT genes were compared between both groups, there was no detected statistically important difference, even-though a TT genotype frequency was 27 (20.8%) versus 17 (26.6%), GT heterozygote genotype frequency was 52 (40%) versus 22 (34.4%), and GG homozygote genotype frequency was 51 (39.2%) versus 25 (39.1%), respectively (p>0.05). NOx, SDMA and ADMA concentrations were significantly elevated in subjects with hemodialysis patients as compared to their corresponding controls. Whereas nitrite was found to be significantly decreased in the patient with peritoneal dialysis. CONCLUSION Not observed any connection between the Glu298Asp polymorphism in the eNOS gene and end-stage Renal Diseases in our study population under different dialysis treatments. However, higher ADMA and SDMA concentrations in subjects with ESRD support the existing hypothesis that NOx overproduction affects endothelial dysfunction. Thus, the reduction of ADMA and SDMA concentrations might play a protective role in ESRD patients.

Serum Cystatin C Levels in COPD: Potential Diagnostic Value and Relation Between Respiratory Functions

Background The predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with cholecystitis has not been established. The aim of this study was to investigate preoperative NLR in patients with cholecystitis and to identify a relevant NLR value that discriminates between simple and severe cholecystitis. Methods This study included 136 patients who under went laparoscopic cholecystectomy due to cholecystitis. The Receiver Operating Characteristic (ROC) analysis was performed to identify the most useful NLR cut-off value in relation to the severity of cholecystitis. The patients were di vided into two groups according to the cut-off NLR value: high NLR group (≥4.18, n=23) and low NLR group (<4.18, n=113). Severe cholecystitis was defined as a state which includes inflammation, empyema, gangrene, perforation of gallbladder, adhesions or difficulty in dissecting Calots triangle. Results In the high NLR group, severe cholecystitis (p<0.0001) and higher C-reactive protein level (CRP) and white blood cells count (WBC) (p<0.0001) were significantly more frequent. There was no difference in homeostatic model assessment-insulin resistance index (HOMA-IR) between both groups before the operation (p<0.634). The incidence of severe cholecystitis was 16.9%. The NLR of 4.18 could predict severe cholecystitis with 78.3% sensitivity and 74.3% specificity. Spearmans correlation revealed significant association between the preoperative NLR and HOMA-IR on day 1, (r=0.254, p=0.030) and between preoperative NLR and CRP on day 1 (ρ=0.355; p<0.0001). Conclusions NLR ≥4.18 was significantly associated with severe cholecystitis. The preoperative NLR in patients under going cholecystectomy due to cholecystitis could be a useful surrogate marker of severe cholecystitis.Summary Background: The aim of this study was to determine the level of serum cystatin C (CysC) in patients with Chronic Obstructive Pulmonary Disease (COPD) during exacerbation and stable periods and to investigate its potential diagnostic value and the relationship between CysC levels and the pulmonary function test (PFT). Methods: One hundred twenty-six patients with COPD (68 in stable periods, 58 during exacerbation periods) and 50 healthy subjects were included in the study. PFT, body mass index (BMI), white blood cell counts, C-reactive protein (CRP), serum urea and creatinine levels were evaluated in both groups of patients. CysC levels were measured in all participants. Results: Serum CysC levels were statistically higher in both COPD groups than the control group (p<0.001 for both) although there was no statistically significant difference between COPD groups (p>0.05). CysC levels showed negative correlation with forced expiratory volume in 1 second (FEV1) and a positive correlation with C-reactive protein (CRP) levels in patients with stable COPD. There was a positive correlation between serum CysC levels and serum urea, creatinine, CRP levels in patients with COPD exacerbation (r=0.333, p=0.011; r=0.260, p=0.049; r=0.414, p<0.01 respectively). When stable COPD and control groups were evaluated, serum CysC had an area under the curve (AUC) in the receiver operating characteristic (ROC) curve of 0.951 (0.909–0.994 95% CI: p<0.001). Conclusions: Our results showed that CysC levels increased in both COPD groups. Increased CysC levels may be related with lung function decline and inflammation in COPD patients. In addition, CysC levels may be a potential indicator for the diagnosis of COPD.

Effects of benfotiamine and coenzyme Q10 on kidney damage induced gentamicin

OBJECTIVE Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. In this study, we investigated whether benfotiamine (BFT) and coenzyme Q10 (CoQ10), could ameliorate the nephrotoxic effect of GM in rats. METHODS Rats were divided into five groups. Group 1 and 2 served as control and sham respectively, Group 3 as GM group, Group 4 as GM+CoQ10 and Group 5 as GM+BFT for 8days. At the end of the study, all rats were euthanized by cervical decapitation and then blood samples and kidneys were collected for further analysis. Serum urea, creatinine, cytokine TNF-a, oxidant and antioxidant parameters, as well as histopathological examination of kidney tissues were assessed. RESULTS Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated serum creatinine, urea and KIM-1 level as compared with the controls. Moreover, a significant increase in serum malondialdehyde, reduced glutathione. Histopathological examination of renal tissue in gentamisin administered group, there were extremly pronounced necrotic tubules in the renal cortex and hyalen cast accumulation in the medullar tubuli. BFT given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and KIM-1 were almost normalized in the GM+BFT group. Benfotiamin treatment was significantly decreased necrotic tubuli and hyalen deposition in gentamisin plus benfotiamin group. CoQ10 given to GM rats did not cause any statistically significant alterations in these nephrotoxicity parameters when compared with GM group but histopathological examination of renal tissue in GM+CoQ10 administered group, CoQ10 treatment was decreased necrotic tubuli rate and hyalen accumulation in tubuli. CONCLUSION The results from our study indicate that BFT supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells.

Does platelet indices play a role in the distinction of pulmonary embolism clinical forms

Aim: The aim of this study is to investigate the changes in platelet indexes, including mean platelet volume (MPV), platelet distribution width (PDW) and platelet count (PC), in patients with acute pulmonary embolism (PE), in addition to evaluating the diagnostic value in clinical forms. Material and methods: The study consisted of 84 patients with PE and the control group consisted of 40 healthy subjects. PE patients were divided into two groups in accordance with the clinical forms as 60 submassive and 24 nonmassive. The differences in platelet count, MPV, PDW, PC, D-dimer, and other indicators were analyzed between the two groups. Venous peripheral blood samples to measure the MPV, PDW and PC were acquired on admission. Results: MPV levels were found to be statistically higher in the submassive group compared to the nonmassive group and the control group (p<0.01 and p<0.001, respectively). PDW levels were found to be statistically higher in the submassive group compared to the non-massive group and control group (p=0.027 and p<0.001, respectively). PC was significantly lower in the submassive group compared to the non-massive group and control group (p=0.022 and p<0.001, respectively). It was determined that a positive correlation existed between the MPV and right ventricular diameter (RVD) (r=0.27, p<0.01). Conclusion: High MPV and PDW levels and low PC may be indicators of the severity of acute PE. Also, the correlation between the MPV and RVD suggests that MPV can be used as a marker of right ventricular function.