Zübeyde Gündüz

The relationship between circulating endothelial microparticles and arterial stiffness and atherosclerosis in children with chronic kidney disease

BACKGROUND Endothelial dysfunction is an important factor in the pathogenesis of atherosclerosis, and endothelial microparticles (EMPs) are considered as markers of endothelial dysfunction. In this study, we aimed to examine the relationship between EMPs and arterial stiffness and atherosclerosis in children with chronic kidney disease (CKD). METHODS This cross-sectional study included 37 dialysis patients (12 haemodialysis, 25 peritoneal dialysis), 33 pre-dialysis patients and 18 healthy controls. Both in vivo and in vitro (HUVECs) evaluations were used for the study. Circulating EMPs were measured by flow cytometry. The carotid artery intima-media thickness (cIMT) and pulse wave velocity (PWV) were measured by using high-resolution ultrasound. Study groups were compared for circulating EMP, cIMT and PWV. The relationship between EMPs and arterial stiffness and atherosclerosis was evaluated. RESULTS The levels of PWV, cIMT, CD144 + EMP and CD146 + EMP in the dialysis group were significantly higher than those in the pre-dialysis and control groups (P < 0.05). Additionally, the levels of cIMT, CD144 + EMP and CD146 + EMP in the pre-dialysis group were significantly higher than those in the control group (P < 0.05). In all CKD patients, the CD144 + EMP was significantly positively associated with blood pressures, age, known duration of disease, CRP and PTH, and was significantly negatively associated with haemoglobin, GFR and albumin. The CD146 + EMP was significantly positively associated with blood pressures, age and CRP. In a multiple linear regression analysis, in the CKD group, cIMT was independently related to mean blood pressure and dialysis duration. PWV was independently related to the CD144 + EMP and mean blood pressure. CONCLUSION Our results suggest that endothelial damage starts in the early stage of CKD, that the endothelial dysfunction becomes overt with the increase of cardiovascular risk factors and that EMPs may be a reliable marker of the subclinical atherosclerosis and arterial stiffness.

Genotype–phenotype correlation in children with familial Mediterranean fever in a Turkish population

Background: The aim of the present study was not only to review clinical and demographic features of child‐onset familial Mediterranean fever (FMF) patients but also to investigate whether there is a phenotype–genotype correlation in the same patient population.

Carotid artery thickness in children and young adults with end stage renal disease

Atherosclerosis is a major cause of morbidity and mortality for ESRD patients and we have little knowledge about the presence and risk factors of atherosclerosis in children with CRF. The measurement of carotid artery intima-media thickness (cIMT) using high-resolution ultrasonography is suggested as an excellent marker of subclinical atherosclerosis. In this study, we aimed to investigate the presence of atherosclerosis and to determine the relationship between atherosclerosis and some risk factors in children and young adults with ESRD. Thirty-four patients with ESRD and 20 controls were included in this study. The measurement of cIMT was performed by using a linear B-mode 7.5-MHz ultrasound transducer. We determined anemia, abnormal calcium/phosphate metabolism, hyperhomocysteinemia, hypertriglyceridemia and increased lipoprotein (a) levels in the ESRD group. The cIMT in the ESRD group was higher than in the control group (P<0.05). SBP, DBP, MAP, LVMI and LVH prevalence were statistically higher in the ESRD group (P<0.05). There were significant positive correlations between cIMT and LVMI, MBP, whereas a significant negative correlation was determined between cIMT and PTH in the ESRD group (P<0.05). When a multiple linear regression analysis was performed with cIMT as a dependent variable and LVMI, MBP, PTH, as independent variables, a significant positive correlation was determined between cIMT and LVMI (P<0.05). In conclusion, we think that arteriopathy occurs in children with ESRD. Left ventricular hypertrophy and hypertension may associate with vascular changes in children and young adults with ESRD. Further investigations are necessary to explain association of LVMI index with cIMT.

Increased endothelial microparticles in obese and overweight children.

Abstract Background: Obesity in children increases the risk of atherosclerosis. Endothelial dysfunction is an important factor in the pathogenesis of atherosclerosis, and endothelial microparticles (EMPs) are considered as markers of endothelial dysfunction. In this study, we aimed to evaluate circulating EMPs in obese and overweight children and to disclose the measure of obesity with the strongest relation with circulating microparticles and carotid atherosclerosis. Methods: This prospective study included 55 obese and overweight children and 23 healthy controls. Insulin resistance was studied. Both in vivo and in vitro human umbilical vein endothelial cell evaluations were used for the study. Circulating EMPs (CD144 and CD146) were measured by flow cytometry. The carotid artery intima-media thickness (cIMT) and left ventricular mass index (LVMI) were measured using ultrasound and echocardiography, respectively. Study groups were compared for anthropometric measurement, insulin resistance, circulating EMP, cIMT, and LVMI. The relationship among overweight, obesity, and circulating EMPs were investigated. Results: Blood pressure, CD144+EMP levels, and LVMI were statistically higher in the patients group than in the control group. The multiple logistic regression analysis and the backward elimination method showed that CD144+EMP and systolic blood pressure had a linear relationship with overweight and obesity. Conclusion: Our results suggest that endothelial damage starts in the early stage of childhood obesity and that obese and overweight children have increased circulating CD144+EMPs, showing that endothelial dysfunction and increased CD144+EMPs may be related to obesity.

SERUM AND CEREBROSPINAL FLUID ZINC LEVELS IN CHILDREN WITH FEBRILE CONVULSIONS

The mechanisms underlying febrile convulsions (FC), which have multiple etiological factors, are not yet clear. The aim of the present study was to determine whether there were any changes in serum and cerebrospinal fluid (CSF) zinc (Zn) levels in children with febrile convulsion during seizures. A total of 102 children were included in the study, with four groups formed as follows: group A, 40 children with FC (aged 9 months to 5 years); group B, 20 children having fever without convulsion (aged 6 months to 5 years); group C, 20 children with afebrile convulsion (aged 6 months to 6 years) and group D, 22 healthy children (aged 5 months to 6 years). Serum and CSF zinc levels for groups A, B and C and serum Zn levels only for group D were measured. The serum Zn levels of 17 children in group A were again measured during healthy periods. Serum Zn levels of groups A, B, C and D had a mean of 0.70 ± 0.10 mg/dL, 1.07 ± 0.08 mg/dL, 1.26 ± 0.32 mg/dL and 1.17 ± 0.21 mg/dL, respectively, and the values of group A were lower than those of the other three groups (P < 0.001). In group B, serum Zn levels were also lower than those of groups C and D (P < 0.05). The CSF Zn levels of groups A, B and C were found to have a mean of 0.07 ± 0.02 mg/L, 0.12 ± 0.02 mg/L and 0.14 ± 0.04 mg/L, respectively. In group A, the CSF Zn levels were lower than those of groups B and C (P < 0.001), and in group B they were lower than those of group C (P < 0.05). For the 17 patients in group A, serum Zn levels during healthy periods (0.87 ±0.10 mg/dL) were found to be higher than the values shortly after seizures, but lower than those of groups B, C and D (P < 0.001). We could not observe any relationship between zinc levels of the serum and CSF and the degree and duration of the fever. These findings suggest that serum and CSF Zn levels decreased during infectious diseases, and that this decrease was more significant in patients with FC.

The effects of dialyzer reuse on plasma antioxidative mechanisms in patients on regular hemodialysis treatment

The effects of antioxidative mechanism are known to be reduced in patients on regular hemodialysis treatment (RHT). The data about the effects of reuse on antioxidative mechanisms are limited. Twelve patients on RHT (age range: 16-50 years) were included in the study. The basal and after 4 months of dialyzer reuse period, plasma antioxidant activity (AOA), myeloperoxidase (MPO) activity, ceruloplasmin (Cp), copper (Cu), transferrin (TF), and sulphydryl group (SH) levels were detected. The basal plasma AOA (110.92 +/- 17.19 microliters), TF (1.23 +/- 0.23 g/l), and SH (307.11 +/- 51.81 mumol/l) levels were lower than the levels of the control subjects (73.75 +/- 9.07 microliters, 2.38 +/- 0.25 g/l, 690.59 +/- 84.18 mumol/l) (p < .001). The basal Cp (0.47 +/- 0.08 g/l) and MPO activity (86.31 +/- 9.57 U/l) levels were higher than the levels of the control subjects (0.34 +/- 0.07 g/l and 65.90 +/- 7.28 U/l) (p < .001). The basal Cu levels (1.19 +/- 0.24 mg/l) were similar to the levels of the control subjects (1.11 +/- 0.13 mg/l) (p > .05). The difference between plasma AOA (83.33 +/- 14.71 microliters), Cp (0.38 +/- 0.08 g/l), and MPO activity (64.43 +/- 10.01 U/l) after the reuse period and the control values were not statistically significant (p > .05). The TF (1.87 +/- 0.15 g/l) levels after the reuse period were significantly lower than the control values (p < .001), although the levels were increased after the reuse period. Our findings may indicate some beneficial effects of hemodialyzer reuse process on plasma antioxidative mechanisms in patients on RHT.

Oxidative stress in hemodialyzed patients and the long-term effects of dialyzer reuse practice.

OBJECTIVES To investigate the existence of an altered oxidant/ antioxidant balance in patients on regular hemodialysis treatment (RHT) and whether there is any effect of dialyzer reuse on oxidative damage and antioxidative mechanism. DESIGN AND METHODS Malondialdehyde (MDA) levels and glutathione peroxidase (GPx) activities in both plasma and erythrocytes, plasma selenium (Se) levels, and erythrocyte superoxide dismutase (SOD) activities of RHT patients were determined at the beginning and end of 4-month reuse period. RESULTS When compared to healthy controls, both plasma and erythrocyte MDA levels were found to be significantly higher in RHT patients before the dialyzer reuse practice; whereas both plasma and erythrocyte GPx activities, erythrocyte SOD activity, and also plasma Se levels were lower in the same patient group than those of controls. When statistical comparison was made on RHT patients between before and after the reuse period, the decreases in MDA levels but increases in the enzyme activities and also an increase in plasma Se levels were observed after the reuse period. However, erythrocyte SOD activities and plasma Se levels measured after the reuse period were not found to be statistically different from the control values; MDA levels still remained elevated above the control values, and GPx activities were not attained to those of controls, after the reuse practice. In addition, positive correlations were found between activities of erythrocyte SOD and GPx enzymes, between GPx and Se levels and negative correlations between the activities of both enzymes and MDA levels in erythrocytes of patients on RHT. CONCLUSION These findings may indicate that dialyzer reuse may provide, at least partly, an improvement on oxidative stress in patients on RHT.

Renal effects of long-term leptin infusion and preventive role of losartan treatment in rats

BACKGROUND Leptin has direct and indirect effects on renal pathophysiological characteristics. In the present study, the effects of long-term leptin infusion on the renal hemodynamics, renal excretory functions, and the expression of transforming growth factor-beta (TGF-beta), plasma endothelin-1 (ET-1) levels, and preventive effects of the angiotensin II type 1 receptor antagonist, losartan, on these renal changes were evaluated. METHODS The study was performed by using forty Wistar albino rats. On day 0, osmotic mini-pumps filled with leptin or placebo were intraperitoneally placed under sterile conditions. The rats in Group L (Leptin group, n=15) and Group LL (Leptin-losartan group, n=15) were given recombinant murine leptin at a rate of 250 ng per hour for 28 days. Control rats (Group C, n=10) were administered placebo at the same infusion rate. The rats in Group LL were also administered losartan (10 mg kg(-1) d(-1)) perorally for 28 days. On day 28, the rats were placed in metabolic cages, and the food and water intakes were determined, and the urine was collected for 24 h. At the end of the study, systolic blood pressure (SBP), diastolic blood pressure (DBP) were determined directly from the left femoral artery, and renal blood flow (RBF) was recorded indirectly using a laser Doppler flow module. RESULTS Leptin infusion did not produce any changes in systemic arterial blood pressures and urinary flow rate. The rates of creatinine (Cr), sodium (Na), and protein excretions of the animals infused leptin were significantly increased. The urinary Cr and Na excretions were decreased, while the urinary protein excretion was normalized with the losartan treatment. The rats infused leptin had also higher circulating ET-1 levels. ET-1 levels were also reversed to the normal values with the losartan treatment. Renal TGF-beta1 expression was determined immunohistochemically, and it was more prominent in the renal tubules from the rats treated with leptin. The losartan treatment had no effect on renal TGF-beta1 expression. CONCLUSIONS Our results indicate that pathophysiological increases in plasma leptin concentrations cause enhanced renal Na, Cr and protein excretions, and high circulating ET-1 levels. Na and Cr excretions were decreased, while proteinuria and plasma ET-1 levels were normalized by losartan treatment, suggesting that renin-angiotensin system activation may have a role in leptin induced renal changes. TGF-beta1 may have an important role in leptin induced nephropathy.

The Effects of Pentoxifylline on Diabetic Renal Changes in Streptozotocin‐Induced Diabetes Mellitus

The aim of the study was to investigate the effects of pentoxifylline on the renal growth, the epidermal growth factor receptor expression, and renal total nitric oxide content in streptozotocin‐induced diabetic rats. Adult male Wistar albino rats were randomly divided into three groups: normal control (the N group), diabetic nephropathy (the DN group), and diabetic nephropathy treated with pentoxifylline at the dosage of 20 mg · kg− 1· d− 1, intraperitoneally (the group DNP). Diabetes was induced by injection of streptozotocin intraperitoneally. The kidney wet weight (KWW) and dry weight (KDW), fractional kidney weight (FKW), glomerular volume (VG), renal tissue protein (RTP) contents, and renal tissue total nitric oxide (NO) production were determined after the rats were sacrificed on 10th day. There was a significant increase in KWW and KWD in the DNP and DN groups when compared to the N group (p = 0.000 for the DNP group, p = 0.000 and p < 0.01 for the DN group). In the DN group, FKW was increased for both wet and dry kidney weight (p < 0.05 and p = 0.001, respectively) while in the DNP group there was increase in FKW only for dry kidney weight. VG was increased in both two diabetic groups (p < 0.05), but this increase was less prominent in the rats treated with pentoxifylline. RTP was significantly decreased in the DNP group when compared with the values in the DN group (p < 0.05). Immunohistochemically epidermal growth factor receptor expression was increased in diabetic rats, and it was not affected by pentoxifylline treatment. In diabetic rats renal content of total NO was decreased (p < 0.05 for the DNP group, p < 0.01 for the DN group). In conclusion, the results provide that pentoxifylline may have some beneficial effects on renal changes in streptozotocin‐induced diabetic rats.

Urinary uric acid : creatinine ratios in healthy Turkish children.

Background:  Determining uric acid : creatinine ratios in random urine samples may be useful to assess the excretion of uric acid in children. Because it was shown that urinary uric acid excretion varies with age and geographic area, it is important to have accurate reference values of uric acid excretion. The aim of the present study was therefore to obtain regional reference values for urinary uric acid : creatinine ratios in healthy Turkish children.