Yildiz Atamer

Changes in serum levels of leptin, cytokines and lipoprotein in pre-eclamptic and normotensive pregnant women.

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)-α, interleukin (IL)-1β, soluble IL-2 receptor (sIL-2R), IL-6 and IL-8 were measured by using a non-radioimmunoassay 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 Students 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-α, IL-1β sIL-2R, IL-6 and IL-8 in the pre-eclamptic 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-B (p > 0.05). Serum levels of TNF-α 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-1β 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 significantly correlated with the serum levels of HDL-cholesterol, LDL-cholesterol and body mass index (BMI) in pre-eclamptic women (r = 0.40, p < 0.01; r =-0.568, p < 0.01; r =-0.30, 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-α, 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.

Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia.

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 pre-eclampsia. 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 Tukeys 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.

Serum leptin levels in asthmatic children treated with an inhaled corticosteroid.

BACKGROUND Recent observations suggest the presence of an interaction between leptin and the inflammatory system; however, there is no adequate knowledge about the role of leptin in atopic states such as asthma. OBJECTIVES To evaluate the potential role of leptin in relation to bronchial asthma and inhaled corticosteroid therapy. METHODS Twenty-three children with mild-to-moderate, newly diagnosed asthma enrolled in this 2-period trial. The control group consisted of 20 age- and sex-matched children. Serum leptin levels were measured in patients at initiation and after 4 weeks of budesonide treatment and were compared with control group measurements. RESULTS Asthmatic children had higher mean +/- SD serum leptin levels at admission (19.3 +/- 5.1 ng/mL) than after budesonide treatment (10.6 +/- 1.6 ng/mL) and vs control group measurements (9.8 +/- 1.6 ng/mL) (P < .001). There was a significant correlation between serum leptin levels before and after budesonide treatment (r = 0.68; P = .007). Mean +/- SD body mass indices in patients and controls were 16.7 +/- 2.1 and 16.9 +/- 2.6 kg/m2, respectively. Serum leptin levels did not correlate with body mass indices before budesonide treatment in the study group (r = -0.13; P = .65) but correlated well after budesonide treatment (r = 0.58; P = .009) and in the control group (r = 0.65; P = .008). CONCLUSIONS The role of leptin elevation in children with asthma might be a regulatory mechanism rather than being etiologic, but a question may be raised whether it is possible that leptin may contribute to poor patient outcomes. Further research, both basic and clinical, is essential to explain the exact mechanism.

Oxidative stress, inflammation and early cardiovascular damage in children with chronic renal failure

The relationship between inflammation, oxidant stress and cardiovascular damage in children with chronic renal failure (CRF) has not previously been investigated. The aim of this study was to investigate markers of oxidative stress, inflammation and early cardiovascular abnormalities. Therefore, erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities; blood glutathione (GSH) and serum malondialdehyde (MDA) levels; C-reactive protein (CRP) and proinflammatory cytokines (IL-6, TNF-α,); and left ventricular masses (LVM) and intima media thicknesses (IMT) were measured in children with CRF. A total of 29 children with CRF (19 nondialysis, 10 peritoneal dialysis) were included. The control group consisted of 25 healthy subjects. CRF children had significantly increased IL-6, TNF-α, CRP and MDA concentrations and decreased SOD, CAT and GSH levels compared with controls (P<0.05). Nondialysis and peritoneal dialysis subgroups had similar oxidative stress and inflammation biomarkers (P>0.05). Erythrocyte CAT was positively correlated with CRP, TNF-α, and IL2-R in the study group. Positive correlations were found between cytokine concentrations, CRP and urea/creatinine levels. Significantly increased LVM and IMT values were found in CRF children (P<0.05). In conclusion, increased oxidant stress and inflammation together with early cardiovascular damage were found in CRF children. Further studies with more patients are needed to verify these results.

Paraoxonase, anti-oxidant response and oxidative stress in children with chronic renal failure

Increased oxidative stress is believed to contribute to an increased risk of cardiovascular disease in uraemia. In children with chronic renal failure (CRF), an anti-oxidant enzyme, paraoxonase (PON), that inhibits oxidation of LDL-cholesterol, has not been previously investigated. In this study we aimed to investigate PON activity, total anti-oxidant response (TAR), total peroxide (TPX), oxidative stress index (OSI) and some pro-oxidant cytokines in 29 children with CRF [mean age 10.2±3.5 years; 19 pre-dialysis, ten on continuous ambulatory peritoneal dialysis (CAPD)] and in 25 control subjects. Children with CRF had lower PON and TAR and higher TPX and OSI values than did controls (P<0.05). Except for lower TAR and serum albumin levels of the CAPD subgroup (P<0.05), other parameters were similar in non-dialysis and CAPD patients (P>0.05). Patients had significant positive correlation between TAR and serum albumin (P<0.05). Serum urea had significant positive correlation with TPX and OSI (P<0.05). Increased oxidative stress and decreased anti-oxidants measured by serum PON activity and TAR were found in children with CRF. We can hypothesize, on the basis of statistical correlations, that low levels of serum albumin and high levels of uraemic metabolites might be responsible for increased oxidative stress in children with CRF. Further studies with larger sample sizes are needed to verify these results.

The relationship between plasma levels of leptin and androgen in healthy and preeclamptic pregnant women

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.

Serum Levels of Leptin and Homocysteine in Women with Polycystic Ovary Syndrome and Its Relationship to Endocrine, Clinical and Metabolic Parameters

We examined the relationship between endocrine, clinical and metabolic parameters in 35 women (mean age 27.3 years) with polycystic ovary syndrome (PCOS) and 30 age- and body mass index-matched normal ovulatory women. In PCOS women, serum leptin, homocysteine, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein-3 levels and the insulin resistance index (HOMA-IR) were significantly higher, while sex hormone-binding globulin and high-density lipoprotein cholesterol levels were lower compared with healthy women. Serum luteinizing hormone (LH), estradiol (E2), androstenedione, testosterone and dehydroepiandrosterone sulphate levels were found to be significantly higher in PCOS women compared with healthy women. The levels of E2, LH and testosterone were positively correlated with leptin levels in PCOS women. Similarly, androstenedione levels and HOMA-IR were positively correlated with homocysteine levels and insulin levels were positively correlated with LH. We conclude that increased homocysteine levels, hyperandrogenaemia, insulin resistance and impaired lipid metabolism contribute to the risk of premature atherosclerosis in PCOS women.

Serum levels of lipids, lipoproteins and paraoxonase activity in pre-eclampsia.

Serum paraoxonase 1 (PON1) activity and the oxidation of lipoproteins were investigated in 35 women with pre-eclampsia and in 35 healthy control women with normal pregnancies. Blood pressure, body mass index (BMI), serum levels of total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and lipoprotein (a) (Lp[a]), and PON1 activity were assessed. There were no significant between-group differences in subject age, gestational age at diagnosis of pre-eclampsia, BMI, serum total cholesterol, triglycerides, LDL and ApoB levels. Mean systolic and diastolic blood pressures and serum Lp(a) were significantly higher in subjects with pre-eclampsia than in controls. Mean serum HDL, ApoA1 and PON1 activity were significantly lower in subjects with pre-eclampsia compared with controls. In conclusion, lipids and oxidized lipoproteins may play important roles in the pathogenesis of pre-eclampsia.

Paraoxonase, total antioxidant response, and peroxide levels in children with steroid-sensitive nephrotic syndrome

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.

Serum levels of leptin, insulin-like growth factor-I and insulin-like growth factor binding protein-3 in women with pre-eclampsia, and their relationship to insulin resistance

The present study was carried out to compare serum levels of leptin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), homeostasis model assessment–(pancreatic β-cell function) (HOMA-(%B)) and homeostasis model assessment–(tissue insulin sensitivity) (HOMA-(%S)) in women with mild and severe pre-eclampsia and normotensive pregnant women; and to evaluate the possible relationships between these parameters in the pathogenesis of pre-eclampsia. Seventy-three women were divided into three groups: group A consisted of 20 normotensive pregnant women (NPW); group B consisted of 25 women with mild pre-eclampsia (MPE); and group C consisted of 28 women with severe pre-eclampsia (SPE). Serum level of leptin was measured by enzyme immunoassay using a commercial kit. Serum levels of IGF-I and IGFBP-3 were measured with a two-site immunoradiometric assay. Serum level of insulin was measured by the electrochemiluminescence immunoassay method. HOMA used indices of pancreatic β-cell function and tissue insulin sensitivity. Differences between groups were compared by one-way analyses of variance and the post hoc Tukey–HSD test for multiple comparisons; however, when a variable was not normally distributed, the Mann–Whitney U test was used. Associations between variables were tested using Pearsons coefficient of correlation. Birth weight was significantly lower (p < 0.001) in the MPE and SPE groups than in the NPW group. Serum levels of leptin and insulin in women with SPE and MPE were significantly higher (p < 0.001) than in NPW. Serum levels of IGF-I and IGFBP-3 were significantly lower in women with SPE and MPE compared with NPW (p < 0.001). The mean HOMA-(%B) level in women with SPE and MPE was significantly higher than in NPW (p < 0.001), whereas the mean HOMA-(%S) level in women with SPE and MPE was significantly lower than in NPW (p < 0.001). In the SPE group, systolic blood pressure correlated significantly with serum levels of IGF-I and leptin (r = 0.375, p < 0.05 and r = 0.495, p < 0.01, respectively). A negative correlation between mean HOMA-(%S) level and serum IGFBP-3 level was noted (r = –0.357, p < 0.05). There was a positive correlation between serum level of IGF-I and mean HOMA-(%B) level in mildly pre-eclamptic women (r = 0.541, p < 0.01). We conclude that pre-eclampsia is associated with insulin resistance; and that existing hyperinsulinemia and insulin resistance in women with pre-eclampsia seem not to correlate with leptin and birth weight, but may correlate positively with IGF-1 and IGFBP-3. Therefore we think that hyperleptinemia, low IGF-I or IGFBP-3, and insulin resistance may contribute to the pathogenesis of pre-eclampsia.