Yasemin Gulcan Kurt

Serum endocan levels as a marker of disease activity in patients with Behçet disease.

BACKGROUND Endocan is a novel human endothelial cell-specific molecule. The central role of leukocytes and endothelial dysfunction in the development of Behçet disease (BD) led us to hypothesize that endocan might be a marker of this disease. OBJECTIVE We investigated the relationship between serum levels of endocan and disease activity in patients with BD. METHODS In all, 33 patients (16 active, 17 inactive) with BD and 35 healthy persons were included in the study. Endocan and C-reactive protein were measured in all subjects. RESULTS Patients with BD had significantly higher serum endocan levels. Mean serum levels of endocan were 1.29 ± 0.60 ng/mL (range: 0.58-2.99) in patients with BD and 0.75 ± 0.16 ng/mL (range: 0.48-1.21) in control subjects (P < .001). In patients with BD, serum endocan levels correlated moderately but significantly with C-reactive protein, erythrocyte sedimentation rate, and disease activity. Receiver operating characteristic curve analysis suggested that the optimum endocan level cut-off point for patients with BD was 0.87 ng/mL, with a sensitivity and specificity of 75.8% and 80%, respectively (area under curve 0.835, 95% confidence interval 0.738-0.932). LIMITATIONS The main limitation of our study is the relatively small sample size. CONCLUSIONS Circulating endocan may be a marker of BD activity.

Plasma endocan levels associate with inflammation, vascular abnormalities, cardiovascular events, and survival in chronic kidney disease

Plasma endocan levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. There are currently no data on endocan in patients with chronic kidney disease (CKD). Therefore, we measured plasma endocan in 251 patients with CKD (stage 1-5) and 60 control individuals. Plasma endocan concentrations correlated with estimated glomerular filtration rate (eGFR), different markers of inflammation (pentraxin 3 and high-sensitivity C-reactive protein), and vascular abnormalities (flow-mediated vasodilation (FMV) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed with respect to plasma endocan. Patients with CKD showed significantly increased plasma endocan (4.7 [IQR 1.9-9.4] compared with controls [IQR 1.1-1.5] ng/ml), with values progressively higher across stages of CKD. On univariate analysis, plasma endocan concentrations correlated negatively with eGFR and FMV, but positively with both markers of inflammation and CIMT. However, on multivariate analysis only high-sensitivity C-reactive protein, FMV, and CIMT remained significantly associated with plasma endocan. On Cox survival analysis, endocan levels were associated with all-cause mortality and CVE in these patients. Thus, plasma endocan increases in the presence of decreasing eGFR and influences all-cause mortality and CVE in patients with CKD independent of traditional and nontraditional risk factors.

Serum Sclerostin and Adverse Outcomes in Nondialyzed Chronic Kidney Disease Patients

BACKGROUND The chronic kidney disease (CKD)-mineral and bone disorder (MBD) syndrome is an important contributor to the CKD-associated cardiovascular disease and high mortality rates. Sclerostin, a protein synthesized in osteocytes, is a potent downregulator of bone metabolism and a novel candidate for the bone-vascular axis in CKD patients. We tested whether serum sclerostin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population. METHODS Serum sclerostin was obtained from 173 CKD (stage 3-5) and 47 control patients, and its concentration was correlated with estimated glomerular filtration rate and to mineral and vascular abnormalities that are present in the CKD evolution. All-cause mortality and CVEs were also analyzed in relation to serum sclerostin values. RESULTS Patients with CKD showed higher sclerostin levels (median 63.5 pmol/L vs 52 pmol/L, P < .001) than controls, with values progressively higher across the CKD stages. In univariate analysis, serum sclerostin concentrations were correlated with gender, estimated glomerular filtration rate, flow-mediated dilatation, and endothelium-independent vasodilatation as markers of endothelial dysfunction and with different serum CKD-MBD-associated parameters. However, in multivariate analysis, only gender, fibroblast growth factor-23, phosphate, flow-mediated dilatation, and cholesterol remained significantly associated with sclerostin levels. During the observational period, there were 19 deaths and 50 CVEs. In survival analysis, different sclerostin levels were associated with all-cause mortality and CVEs in these patients. CONCLUSIONS This is the first study that shows that serum sclerostin values are associated, even after multiple adjustments, with fatal and nonfatal CVEs in a nondialyzed CKD population.

The association between serum levels of neopterin and number of depressive episodes of major depression

BACKGROUND There is an interaction between the immune system and the central nervous system by means of hormones, peptides, and neurotransmitters. The aims of the present study were to determine whether the serum neopterin levels in patients with major depression (MD) differ from a healthy control group and to investigate the relationship between previous MD episodes and serum neopterin levels. METHODS Thirty patients who were admitted to the GATA Psychiatry Outpatient Clinics and were diagnosed with MD according to DSM-IV, and who agreed to participate in the study, were included in the study. Twenty-six healthy volunteers matched for age, gender, and level of education who agreed to participate in the study were served as controls. Peripheral venous blood samples were obtained from the patients and the control group for complete blood count, routine biochemistry, and the detection of serum neopterin levels. The analyses were performed in the laboratory of the GATA Department of Biochemistry. RESULTS There was no significant difference between the MD group and the healthy controls with respect to age, level of education, smoking, and gender. Serum neopterin levels of the MD group who had experienced two or more episodes were higher than the first-episode group and the control group. Age of onset and the number of previous episodes had an independent impact on serum neopterin levels in MD patients, while smoking did not show any effect. CONCLUSION In the present study, the neopterin levels of patients who had experienced two or more episodes were higher than the first-episode depressive group and healthy control group. It was also found that the number of previous depressive episodes and the ages of the MD cases had an independent effect on serum neopterin levels.

Improving proteinuria, endothelial functions and asymmetric dimethylarginine levels in chronic kidney disease: ramipril versus valsartan.

Background: The aim of this study was to find out whether the beneficial effects of the renin-angiotensin-aldosterone system (RAS) blockage in chronic kidney disease (CKD) has any relation with the alteration of asymmetric dimethylarginine (ADMA) levels. Methods: Sixty-six nondiabetic patients with CKD and proteinuria and 36 healthy subjects were enrolled. Patients were treated with either ramipril 5 mg daily or valsartan 160 mg daily for 3 months. Proteinuria, ADMA, symmetric dimethyl arginine (SDMA), flow-mediated dilatation (FMD) and HOMA index measurements were performed both before and after the treatment. Results: ADMA, SDMA, hsCRP levels, HOMA index and proteinuria of patients were significantly higher (p < 0.001 for all) and FMD, L-arginine and L-arginine/ADMA ratio in CKD were significantly lower than controls. According to the multiple regression analysis, proteinuria levels were independently related to ADMA and SDMA levels. Conclusion: Both drugs were equally effective in reducing elevated ADMA levels and improving endothelial dysfunction in CKD patients.

The relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy.

Abstract Objectives. Diabetic nephropathy (DN) is a major manifestation of microangiopathy in patients with Diabetes Mellitus (DM). Inflammation is one of the major factors in the formation of endothelial dysfunction. Endothelial dysfunction is a major contributor to the complications of DM. The aim of the present study was to investigate the possible relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy. Materials and methods. Plasma TNF-α and IL-6, pro-inflammatory cytokines, concentrations were measured in 25 patients with DN and in 30 diabetic control subjects. Also, we evaluated the markers of endothelial dysfunction such as flow mediated dilatation (FMD), nitrate-mediated dilatation (NMD) and carotid intima-media thickness (CIMT). Results. TNF-α, IL-6 and high-sensitivity C-reactive protein concentrations were significantly higher (p = 0.012, p = 0.006 and p < 0.001, respectively) in the patients with DN than the controls. And, urinary protein concentrations were significantly higher (p < 0.001) but eGFR levels were significantly lower (p < 0.001) in the patients with DN. FMD was significantly lower in DN patients (p < 0.001). We have observed that FMD correlated negatively with body mass index (r = −0.424, p < 0.05). And there was also a positive correlation between TNF-α and urinary protein concentrations in the patients with DN (p < 0.05). Conclusion. TNF-α, IL-6, hsCRP and urinary protein concentrations are higher in the DN patients. There were no correlations among pro-inflammatory cytokines concentrations and markers of vascular endotelial disfunction. These findings did not show vascular endothelial dysfunction, but may indicate glomerular endothelial dysfunction.

Beneficial Effects of N-Acetylcysteine and Ebselen on Renal Ischemia/Reperfusion Injury

Abstract Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney. Materials and methods: Forty male Sprague–Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations. Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups. Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.

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.

Simultaneous determination of cyclosporine A, tacrolimus, sirolimus, and everolimus in whole-blood samples by LC-MS/MS.

Objectives. Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and everolimus (RAD) are immunosuppressive drugs frequently used in organ transplantation. Our aim was to confirm a robust sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of CyA, TRL, SIR, and RAD in whole-blood samples. Materials and Methods. We used an integrated online solid-phase extraction-LC-MS/MS system and atmospheric pressure ionization tandem mass spectrometry (API-MS/MS) in the multiple reaction monitoring (MRM) detection mode. CyA, TRL, SIR, and RAD were simultaneously analyzed in whole blood treated with precipitation reagent taken from transplant patients. Results. System performance parameters were suitable for using this method as a high-throughput technique in clinical practice. The high concentration of one analyte in the sample did not affect the concentration of other analytes. Total analytical time was 2.5 min, and retention times of all analytes were shorter than 2 minutes. Conclusion. This LC-MS/MS method can be preferable for therapeutic drug monitoring of these immunosuppressive drugs (CyA, TRL, SRL, and RAD) in whole blood. Sample preparation was too short and simple in this method, and it permits robust, rapid, sensitive, selective, and simultaneous determination of these drugs.

Metformin decreases circulating acylation-stimulating protein levels in polycystic ovary syndrome.

Aim. There are no studies that examine the circulating acylation-stimulating protein (ASP) levels in patients with polycystic ovary syndrome (PCOS). The present study was designed to determine the ASP levels in PCOS and to evaluate the effect of metformin on plasma fasting ASP concentrations. Methods. Twenty women with PCOS and 20 healthy controls matched for age and body mass index (BMI) were included in the study. We determined ASP and other biochemical parameters before and after treatment. Results. Baseline levels of plasma ASP, complement 3 (C3), waist-to-hip ratio (WHR), homeostasis model assessment–insulin resistance index (HOMA-IR), fasting insulin, triglycerides (TG) and very-low-density lipoprotein cholesterol (VLDL-C) were significantly higher in patients than in controls. After 3 months of metformin treatment, BMI, WHR, ASP, C3, fasting glucose, fasting insulin, HOMA-IR, total cholesterol, TG, VLDL-C and free testosterone decreased significantly, whereas apolipoprotein A-I and high-density lipoprotein cholesterol increased significantly. Conclusions. The major novel information of the present study is that ASP and C3 values are markedly increased in non-obese patients with PCOS, with a decrease evidenced with metformin treatment.