Kemal Erbil

Endothelial functions improve with decrease in asymmetric dimethylarginine (ADMA) levels after renal transplantation.

Background. Chronic kidney disease (CKD) is associated with increased cardiovascular events. The relationships between the markers of inflammation and endothelial dysfunction were investigated both before and after living donor kidney transplantation. Methods. Twenty-seven renal transplant patients were studied. Eleven patients (six male, five female) were on cyclosporine A, whereas 16 patients (nine male, seven female) were treated with tacrolimus based regimes. Twenty-seven subjects (12 males, 15 females) were studied as controls. Plasma adiponectin, high sensitive C reactive protein (hsCRP), Asymetric dimethyl arginine (ADMA) levels were studied before transplantation and on days 1, 3, 7, 14, and 28. The brachial artery flow mediated dilatation (FMD) was studied before transplantation and on the 28th day. Results. Serum hsCRP and ADMA levels decreased significantly from the first posttransplantation day on each measurement (P<0.001 for all) while the decrement of plasma adiponectin started in the third day (P<0.001 for all). The FMD was lower in the patients than the control group (P<0.001) and improved significantly in the 28th day of transplantation (P<0.001). Conclusions. The results indicate that ADMA is associated with FMD in CKD both before and after kidney transplantation. Endothelial functions improve at the very beginning of the posttransplantation period with accompanying reduction in ADMA and hsCRP levels.

High serum levels of neopterin in patients with Crimean–Congo hemorrhagic fever and its relation with mortality

Summary Objective Neopterin is generated and released in increased amounts by macrophages upon activation by interferon-gamma during cellular immune response. In this study, we aimed to investigate serum neopterin levels in patients with Crimean–Congo hemorrhagic fever (CCHF) and its clinical significance as a predictor factor of mortality. Methods Neopterin concentrations on the first day of hospitalization were measured in serum samples from 51 CCHF patients. Serum neopterin levels and other clinical–laboratory parameters for fatal and nonfatal CCHF patients were compared. Results Serum neopterin levels (73.22±54.30nmol/L) were highly elevated in all CCHF patients (p <0.0001) with higher levels in fatal group (153.66±81.34nmol/L, p =0.0001) compared to nonfatal disease (55.99±24.09nmol/L). In univariate analysis, the level of neopterin on the first day of hospitalization, bleeding, platelet count, aspartate transferase and lactate dehydrogenase were associated with mortality. In multivariate analysis, only the serum level of neopterin was associated with mortality. As a mortality risk factor, area under the curve was 0.939 (p =0.0001, 95% confidence interval: 0.85–1.00). Conclusions In this first study of serum neopterin levels for CCHF, elevated serum neopterin level showing strong activation of monocytes/macrophages was a risk factor for CCHF.

Pentraxin 3 as a potential biomarker of acetaminophen-induced liver injury.

OBJECTIVE Overdose of acetaminophen (APAP) can lead to severe liver injury in humans and experimental animals. Pentraxin-3 (PTX-3) is produced and released by several cell types. In this study, we aimed to evaluate whether PTX-3 is a potential biomarker in the identification of APAP-induced liver injury. MATERIALS AND METHODS Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1 and APAP-2 groups. APAP-1 (1 g/kg) and APAP-2 (2 g/kg) group rats were given APAP by gastric tube. Liver tissues and blood samples were obtained for biochemical and histopathological analysis. Biochemical parameters, plasma and liver PTX-3 levels and degree of liver necrosis were measured in all groups. RESULTS APAP treatments caused necrosis in liver and accompanied by elevated liver PTX-3 levels after 48 h. In APAP-1 and APAP-2 groups when compared with control group (7.5±3.3 ng/mg protein), mean liver PTX-3 concentrations were 14.1±3.0 (p=0.032) and 28.5±8.2 (p<0.001) ng/mg protein, respectively. All rats (100%) in the APAP-2 group had the degree 3 liver necrosis. However 10%, 40% and 50% of rats had the degree 1, the degree 2 and the degree 3 liver necrosis in the APAP-1 group, respectively. The degrees of liver necrosis of the APAP-1 and APAP-2 groups were higher than the group of control (p<0.001 and p<0.001, respectively). CONCLUSIONS PTX-3 may have a role in the APAP-induced liver injury in the rats. The elevated liver PTX-3 in the APAP-induced hepatic necrosis might be a marker of acute histological liver damage. Further prospective studies are necessary to clarify the prognostic value of liver PTX-3 for prediction of histological hepatic necrosis in the APAP-induced liver injury.

The association between neopterin and acetaminophen-induced nephrotoxicity

Introduction: In large dosages, acetaminophen (APAP) produces acute kidney necrosis in most mammalian species. High neopterin levels have been accepted as strong indicators for the clinical severity of some diseases. In this study, we aimed to evaluate whether neopterin is a biomarker in the identification of APAP-induced nephrotoxicity. Materials and Methods: Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1, and APAP-2 groups. APAP-1 and APAP-2 group rats were given a single dose of 1 and 2 g/kg body weight of APAP by gastric tube, respectively. Kidney tissues and blood samples were obtained for biochemical and histopathological analyses. Biochemical parameters, serum and kidney neopterin levels, and the grade of tubular injury were compared in the control, APAP-1, and APAP-2 group animals. Results: APAP treatments caused tubular necrosis in the kidney and increase in serum creatinine concentrations accompanied by elevated serum and kidney neopterin levels. In the rats of groups APAP-1 and APAP-2 when compared with that of the control group (109.1 pmol/mg protein), median kidney neopterin concentrations were 162.1 (p = 0.089) and 222.2 (p < 0.001) pmol/mg protein, respectively. The grade of tubular injury of the APAP-1 and APAP-2 groups was higher than the group of control (both p < 0.001). Conclusions: Serum and kidney neopterin levels could be sensible alternative to evaluate the risk to have nephrotoxicity because of APAP overdose. The elevated serum and kidney neopterin in the APAP-induced tubular necrosis might be a marker of acute histological kidney injury.

The levels of nitric oxide and asymmetric dimethylarginine in the rat endometriosis model

Aim:  To investigate the levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA) in all the rat endometriosis models.

The plasma levels of soluble P-selectin in subjects with prediabetes

Prediabetes has been associated with an increased risk of cardiovascular disease and mortality. Soluble P‐selectin (sP‐selectin) is an index of platelet activation and also a risk factor for future vascular events. sP‐selectin levels were investigated in prediabetic subjects who had no confounding factors such as hypertension, obesity or dyslipidaemia. sP‐selectin, hsCRP levels and HOMA‐IR indexes were measured in 40 prediabetic subjects (n = 24 for IFG and n = 16 for IGT) and age‐, sex‐ and BMI‐matched 40 healthy controls. sP‐selectin levels in prediabetic subjects were not significantly different compared with those in controls (p = 0.12). Prediabetic group had similar hsCRP (p = 0.29), higher HOMA‐IR indexes (p < 0.001) and lower HDL cholesterol levels (p = 0.001) when compared with healthy controls. The power of the study was 0.93 for sP‐selectin, 0.7 for hsCRP and 1.0 for HOMA. Our data suggest that sP‐selectin may not contribute to the prothrombotic state as well as the accelerated atherogenesis associated with prediabetes.

Soluble Vascular Endothelial Growth Factor Receptor 1 in Human Breast Milk

Background/Aims: Vascular endothelial growth factor (VEGF) is a potent proangiogenic protein that activates VEGF receptor (VEGFR-1, VEGFR-2) tyrosine kinases expressed by vascular endothelial cells. A soluble truncated form of VEGFR-1 (sVEGFR-1) binds to VEGF as strongly as full-length VEGFR-1 and inhibits VEGF activity. sVEGFR-1 can be detected in mouse and human plasma but in human milk sVEGFR-1 has not been described previously. Methods: We measured sVEGFR-1 and VEGF in human milk and examined how the concentration varied with gestational age and the duration of lactation after birth. Human milk samples were collected from 29 mothers of preterm (<37 weeks) and from 29 mothers of term (>38 weeks) infants at days 3, 7 and 28 postpartum. Results: The sVEGFR-1 and VEGF concentrations were greater in the human milk of mothers of preterm compared to term neonates (p < 0.05). Furthermore, the concentrations of sVEGFR-1 and VEGF were decreasing during postpartum days 3, 7 and 28. The concentration of sVEGFR-1 showed a positive correlation with the concentration of VEGF in human milk (r = 0.479 and p < 0.001). Conclusion: sVEGFR-1 is present in human milk and has a role in angiogenesis.

Soluble CD40 ligand levels in patients with hypertension

CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte communication, but also associates with chronic inflammation and atherothrombosis. High soluble CD40L (sCD40L) levels were reported in dyslipidemia, diabetes mellitus, and coronary disease. So far, there are no data about sCD40L levels in hypertension. We investigated sCD40L and high sensitive C reactive protein (hsCRP) levels in 30 nonobese young hypertensive men and 30 matched controls. sCD40L and hsCRP levels were not different, and there were no correlations between blood pressure and sCD40L or hsCRP levels. These results might indicate lack of any inflammatory state in new onset hypertension.

Effects of etanercept on urine neopterin levels in patients with psoriasis in a controlled, open-label study

Neopterin is an immunological marker of cellular immune activation. Etanercept is a tumor necrosis factor‐α (TNF‐α) antagonist that decreases excessive levels of TNF‐α associated with inflammatory disease down to physiological levels. The objective of this study was to investigate urine neopterin levels in psoriatic patients treated with etanercept, to study the effect of etanercept as a TNF‐α blocker on urine neopterin levels. Urine neopterin levels and urine neopterin/creatinine ratios were measured by high‐performance liquid chromatography in 22 patients with psoriasis before and after treatment with etanercept. Results were compared with a group of 20 healthy volunteers, and 20 patients with inflammatory skin diseases as control groups. Urine neopterin levels, neopterin/creatinine ratios and Psoriasis Area and Severity Index (PASI) scores were evaluated at baseline, and the 12th and 24th week after treatment. Urine neopterin levels were significantly elevated in the psoriatic group compared with control and inflammatory skin diseases groups (P < 0.05). Urine neopterin levels were significantly reduced after etanercept treatment. Statistically we did not find any correlation between neopterin levels and PASI scores. Our findings indicate that urine neopterin concentrations may reflect the disease activity in psoriasis, and may be used as a marker for monitoring disease activity and response to treatment with etanercept in psoriatic patients.

Neopterin levels in nonreplicative HBV carriers

The aim of this study was to determine the existence of immune activation by measuring neopterin in HBV (Hepatitis B virus) carriers with viral load (HBV DNA) less than 5 pg/ml. Forty-three subjects and 56 healthy controls were included in the study. Neopterin levels of were compared. ALT and ALP levels in one patient and AST levels in two patients were found minimally higher than upper limit, and GGT levels were within the reference range in all patients. Neopterin levels in the patient group and in the controls were 159.97+/-13.39 and 84.10+/-11.45 nmol/l, respectively (P<0.0001). The difference between the two groups was statistically significant (P<0.0001). In conclusion, the increased neopterin levels of HBV carriers might be the indicators of the effect of cellular immunity. This increase might also implicate a background inflammation based on mainly cellular immunity that exists within the liver.