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    Anti-oxidant status in relation to lipoproteins, leptin and pro-inflammatory cytokines in children with steroid-sensitive nephrotic syndrome
    (Blackwell Publishing Asia, 2004) Ece, A; Atamer, Y; Gürkan, F; Bilici, M; Koçyigit, Y
    Background: Reactive oxygen species and cytokines are reported to play a role in the proteinuria of nephrotic syndrome. The aim of this study was to investigate indirect evidence of oxidant activity together with leptin, lipoproteins and pro-inflammatory cytokines in children with steroid-sensitive nephrotic syndrome. Methods: A total of 40 children with steroid-sensitive nephrotic syndrome (20 with newly onset or relapse comprised group I and 20 in remission while receiving steroids comprised group II) and 20 sex and age matched healthy control children were included. The following indirect parameters of oxidant activity were determined: serum malondialdehyde, erythrocyte superoxide dismutase, catalase and whole-blood-reduced glutathione. Serum leptin, lipids and lipoproteins were also determined. Results: Similar glutathione, increased malondialdehyde levels and decreased superoxide dismutase and catalase activity were observed in group I patients compared with controls. There was no significant difference in these variables between group I and group II (P > 0.05). Tumour necrosis factor-alpha and interleukin-6 concentrations were similar in patients and controls. Concentrations of interleukin-1beta and interleukin-8 were higher in the active phase of nephrotics compared with controls (P < 0.05). Significant positive correlations were found between malondialdehyde and interleukin-1beta, interleukin-6, leptin and lipoprotein (a) (P < 0.05). There were significant negative correlations between anti-oxidants and leptin, lipoprotein (a) and several cytokines (P < 0.05). Conclusions: Changes in the concentrations of malondialdehyde, superoxide dismutase, catalase and glutathione are compatible with increased amounts of oxidation in steroid-sensitive nephrotic syndrome. Leptin and pro-inflammatory cytokines may be related to excessive protein permeability in nephrotic syndrome.
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    Changes in serum levels of leptin, cytokines and lipoprotein in preeclamptic and normotensive pregnant women
    (Parthenon Publishing Group, 2004) Koçyigit, Y; Atamer, Y; Atamer, A; Tuzcu, A; Akkus, Z
    The aim of this study was to investigate the changes in serum levels of leptin, cytokines and lipoproteins in women with pre-eclampsia and to evaluate their clinical significance in the pathogenesis of pre-eclampsia. We performed a prospective study involving 45 women with pre-eclampsia in the third trimester of pregnancy and 30 normotensive women in the third trimester of pregnancy. Serum level of leptin was measured by enzyme immunoassay using a Cayman chemical kit, Serum levels of tumor necrosis factor (TNF)-alpha, intertleukin (IL)-1beta, soluble IL-2 receptor (sIL-2R), IL-6 and IL-8 were measured by using a nonradioimmunoassay chemiluminescent method. Serum lipid concentrations were measured by an Abbott Aeroset (USA) autoanalyzer. Serum levels of apolipoprotein (Apo)A-I and ApoB were evaluated by nephelometrics assays. Differences between groups were evaluated with Student's unpaired t test and, when a variable was not normally distributed, the Mann-Whitney U test was used. The relationship between the variable was explored by the Pearson correlation test. Serum levels of leptin, TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 in the preeclamptic women were significantly higher than in normotensive women (p < 0.001). In the pre-eclamptic women serum levels of triglycerides, total cholesterol and low-density lipoprotein (LDL)-cholesterol were significantly increased (p < 0.001), while high-density lipoprotein (HDL)-cholesterol and Apo-A were significantly decreased compared to levels in normotensive pregnant women (p < 0.001). No significant differences were noted between the groups in Apo-? (p > 0.05). Serum levels of TNF-? were significantly correlated with the serum levels of IL-6, IL-8, triglycerides, sIL-2R, Apo-A and hematocrit in pre-eclamptic women (r = 0.418, p < 0.05 - r = 0.389, p < 0.01; r = 0.312, p < 0.05; r 0.318, p < 0.05; r 0.340, p < 0.05 and r = 0.41, p < 0,01, respectively). A negative correlation was seen between serum level of leptin and both IL-1? and Apo-A in pre-eclamptic women (r = 0.44, p < 0.05; r = 0.39, p < 0.05, respectively). Serum levels of IL-6 were also signficantly correlated with the serum levels of HDL-cholesterol, LDL-cholesterol and body mass index (BMI) in preeclamptic women (r = 0.40, p < 0.01; r = 0.568, p < 0. 0 1; r 0. 3 0, p < 0. 05, respectively). In addition, serum level of IL-8 were significantly correlated with the serum levels of HDL-cholesterol, total cholesterol and BMI in pre-eclamptic women (r = 0.368, p < 0.05; r = 0.513, p < 0.01 and r = 0.41, p < 0.01, respectively). We found that the pre-eclampsia associated with increases in serum levels of leptin, TNF-?, cytokines, triglycerides, total cholesterol and LDL-cholesterol was associated with a significant reduction in serum levels of HDL-cholesterol and Apo-A. These association may be due to the abnormal lipid metabolism and immune activation involved in the pathogenesis of this disease.
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    Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia
    (Elsevier Sci Ireland Ltd, 2005) Atamer, Y; Koçyigit, Y; Yokus, B; Atamer, A; Erden, AC
    Objective: To investigate the changes in enzyme activities of erythrocyte superoxide dismutase (SOD), catalase, and placental glutathione peroxidase (GSH-Px), and analyze the levels of serum malondialdehyde (MDA), copper (Cu), zinc (Zn), selenium (Se), leptin and placental MDA and glutathione (GSH). Study Design: Cross-sectional prospective study consisting of 32 preeclamptic (PE) pregnant, 25 non-pregnant (NP) women, 28 healthy pregnant (HP) women. Levels of lipid peroxides in serum and placenta, and activities of SOD, catalase in erythrocyte and placental GSH level, placental GSH-Px activity were measured by spectrophotometric methods. Serum levels of Cu, Zn, Se measured by atomic absorption spectrophotometry. Serum levels of leptin was measured by enzyme immunoassay by using the Cayman chemical kit. One-way analysis of variance and post hoc Tukey-HSD test and Pearson correlation test were used for the statistical analyses. Results: Serum levels of MDA, Cu, Leptin were markedly higher (P < 0.001); and serum level of Se was markedly lower (P < 0.001) in PE women compared with HP women and NP women. Also, placental MDA level was higher (P < 0.001) and placental GSH-Px activity was lower in PE women compared with HP women. In preeclamptic women erythrocyte catalase activity was markedly increased (P < 0.001), while erythrocyte SOD activity was markedly decreased (P < 0.001) compared to HP women and NP women. Placental GSH level was decreased compared to HP women (P < 0.001). Serum level of Zn was markedly decreased compared to NP women (P < 0.001) but no significant difference was observed in PE pregnant when compared with HP women (P > 0.05). Placental MDA level in PE women had significant negative correlation with serum Se level (r = -0.353, P < 0.05). A negative correlation was found between erythrocyte catalase activity with birth weight (r = -0.528, P < 0.001). Also, there were a significant negative correlation between serum levels of Cu and Se in the preeclamptic women (r = -0.407, P < 0.05). Conclusion: Our data demonstrate that elevation of lipid peroxides together with impaired antioxidant defense mechanisms and status of trace metals and the presence of possible interrelationship and crosstalk between those parameters may be related at least partly to the pathogenesis of preeclampsia. Additionally, lipid peroxides and blood oxidative imbalance could be part of the cytotoxic mechanisms leading to endothelial cell injury. (c) 2004 Elsevier Ireland Ltd. All rights reserved.
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    Paraoxonase, total antioxidant response, and peroxide levels in children with steroid-sensitive nephrotic syndrome
    (Springer, 2005) Ece, A; Atamer, Y; Gürkan, F; Davutoglu, M; Koçyigit, Y; Tutanç, M
    Reactive oxygen species (ROS) are reported to play a role in inducing the proteinuria of nephrotic syndrome (NS). This study investigated paraoxonase (PON), total antioxidant response (TAR), and oxidant total peroxide together with serum proteins and lipoproteins in children with steroid-sensitive NS. The study included 40 children with steroid-sensitive NS (21 with acute-period NS in group I, 19 nonproteinuric while receiving steroids in group II) and 22 sex- and age-matched formerly nephrotic children in remission weaned from steroids (group III). The following parameters were determined: total peroxide, oxidative stress index (OSI), PON and TAR. Serum proteins and lipoproteins were also determined. Patients in the active phase of NS had significantly lower PON and TAR levels and higher OSI and total peroxide values than those in full remission; no differences were found in PON, TAR, or OSI values of groups I and II. Significant correlations were found between PON, TAR, and total peroxide. Serum total protein had a significantly positive correlation with PON and negative correlation with total peroxide in acute-period NS patients. Our results demonstrate greater oxidative stress and decreased antioxidants in the active phase of steroid-sensitive NS and while patients receive steroids than during full remission. Low-dose alternate-day steroids do not seem to decrease oxidative stress even while proteinuria ceases. Despite some conflicting data increased oxidation and/or decreased antioxidant response may be related to the pathogenesis of steroid-sensitive NS.
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    Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia
    (Taylor & Francis Ltd, 2005) Bayhan, GH; Koçyigit, Y; Atamer, A; Atamer, Y; Akkus, Z
    Aims. To evaluate changes in lipid profile, serum levels of malondialdehyde (MDA) and lipoprotein(a) (Lp(a)) and placental MDA in preeclamptic women, and to evaluate the atherogenic role of these changes in the pathophysiology of preeclampsia. Method. A cross-sectional study was performed in 20 normal pregnant women, 25 women with mild preeclampsia and 28 women with severe preeclampsia in the third trimester. MDA, which is the endproduct of lipid peroxidation, was measured in placental tissue by the thiobarbituric acid (TBA) method of Ohkawa and colleagues and in serum by the TBA method of Asakawa and Matsushita. Serum lipid levels were measured by with an autoanalyzer, serum apolipoprotein (Apo) A-I and Apo B were measured by nephelometric assay and serum Lp(a) level using a nephelometric agglutination assay method. In preeclamptic and normal pregnant women, multiple comparisons between groups were performed by one-way analysis of variance supplemented with Tukey's HSD post hoc test. The association between placental and serum concentrations among groups was analyzed using the Pearson correlation test. Results. Serum levels of MDA, Lp(a), total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and placental MDA were significantly higher, and high-density lipoprotein cholesterol (HDL-C) and Apo A-I levels were significantly lower, in severely preeclamptic and mildly preeclamptic women than in the normal pregnant women, but no difference was observed in Apo B among groups. Serum level of Lp(a) was positively correlated with body mass index in severely preeclamptic women (r = 0.489:, p = 0.008). A significant positive correlation was also found between serum level of MDA and systolic blood pressure in women with severe preeclampsia (r = 0.375, p = 0.049). Conclusions. Our findings suggest that high Lp(a), lipid peroxidation, LDL-C and TG, and low HDL-C and Apo A-I levels, are important risk factors for atherosclerosis among preeclamptic women.
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    The relationship between plasma levels of leptin and androgen in healthy and preeclamptic pregnant women
    (Blackwell Munksgaard, 2004) Atamer, Y; Erden, AC; Demir, B; Koçyigit, Y; Atamer, A
    Background To clarify the role of leptin and androgens in the pathogenesis of preeclampsia, we wanted to assess role of maternal leptin in women with severe and mild preeclampsia and the effects of sex steroid hormones on leptin production. Methods. The groups consisted of 40 healthy pregnant women (HPW) as well as 55 pregnant women with severe preeclampsia (SPE) and 41 pregnant women with mild preeclampsia (MPE). No significant differences were observed between the three groups regarding age, gestational age and body mass index (BMI). Plasma leptin, total testosterone (T), estradiol (EA dehydroepiandrosterone sulfate (DHEAS) and androstenedione (A) levels were measured. Statistical analysis was achieved with one-way analysis of variance (ANOVA) followed by post hoc multiple comparisons with the Tukey honestly significant difference (HSD) test by using SPSS for Windows statistical computer program, and the Pearson's coefficient of correlation was calculated. Results. The plasma level of leptin was significantly increased in the SPE and MPE groups (p < 0.001), whereas the plasma level of T was significantly increased only in the SPE group (p < 0.001). However, there was no significant difference in plasma levels of DHEAS among the three groups (p < 0.05). The plasma level of A was significantly decreased in the MPE group (p < 0.05). There was no significant difference in the plasma level of E-2 in the MPE and SPE groups (p < 0.05). There was a significant positive correlation between the plasma levels of leptin and E-2 in the MPE group (r = 0.41, P < 0.001). Conclusion. We concluded that the elevated plasma levels of leptin and testosterone could contribute to the endothelial dysfunction involved in the pathogenesis of preeclampsia, and that estradiol might lead to an increase in the plasma levels of leptin.