Yuksel Kocyigit

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.

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 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.

Anti-oxidant status in relation to lipoproteins, leptin and pro-inflammatory cytokines in children with steroid-sensitive nephrotic syndrome.

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.

Relationship between Leptin, Insulin Resistance, Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-3 in Patients with Chronic Kidney Disease

This study examined the relationship between leptin, insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3) and insulin resistance in patients with chronic kidney disease (CKD). Levels of leptin, insulin, IGF-1, IGFBP-3 and common routine parameters were measured in 45 patients (23 males and 22 females) with CKD and 45 healthy controls matched for age, gender and body mass index. IGF-1 and IGFBP-3 levels were measured using a two-site immunoradiometric assay. Leptin levels were measured using an enzyme-linked immunosorbent assay. A homeostasis model assessment computer-solved model was used to assess insulin resistance (HOMA-IR). Levels of serum leptin, insulin, IGF-1, IGFBP-3 and HOMA-IR were significantly increased in patients with CKD compared with healthy subjects, whereas fasting blood glucose was not significantly different between the two groups. In patients with CKD, the serum leptin level was significantly correlated with IGF-1, IGFBP-3 and HOMA-IR. In conclusion, this study suggests that there is an interaction between leptin, IGF-1, IGFBP-3 and insulin resistance in patients with CKD.

The role of homocysteine, asymmetric dimethylarginine and nitric oxide in pre-eclampsia.

Nitric oxide (NO) contributes to vasodilatation that is observed during normal pregnancy. Hyperhomocysteinaemia (HHcy) is a vascular risk factor associated with placental microvascular diseases and pre-eclampsia. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (NOS) has been linked to endothelial dysfunction. Maternal ADMA has been reported to be higher in women with pre-eclampsia and HHcy leads to accumulation of ADMA. The aim of this presented study is to evaluate the alterations of plasma homocysteine, ADMA and NO levels in mild pre-eclampsia. A total of 40 pre-eclamptic women and 40 healthy controls were included into the study. Mean systolic and diastolic blood pressure, mean serum homocysteine and ADMA levels were significantly higher and NO level was lower in patients. Serum homocysteine, ADMA and NO levels found to be correlated among them and with blood pressure. In conclusion, we found that homocysteine and ADMA levels were increased and NO levels decreased in pre-eclampsia.