Yuksel Aliyazicioglu

Endothelin levels in Henoch-Schonlein purpura

Abstract. Henoch-Schonlein purpura (HSP) is one of the most common types of vasculitis disorders seen in childhood and is characterized by a rash, arthritis, abdominal pain, and renal involvement. Although HSP is an immunoglobulin A (IgA) related immune complex disease, the pathogenesis has not been fully elucidated. Cytokines have been implicated in the pathogenesis, but endothelins (ET) – vasoconstrictor hormones produced by endothelial cells – have not been studied in patients with HSP. In a controlled study, we measured ET-1 levels in children with HSP during the acute and remission phases. ET-1 levels were significantly higher in the HSP patients during the acute phase compared with the control group and the HSP patients in the remission phase. There was no correlation between ET-1 levels and disease severity, acute phase reactant response, or morbidity. The role of endothelins and other cytokines in the pathogenesis of HSP needs to be further explored.

Assessment of Genotoxicity in Rats Treated With the Antidiabetic Agent, Pioglitazone

Pioglitazone (PIO), a member of the thiazolidinedione class of antidiabetic agents, specifically targets insulin resistance. Drugs of this class act as ligands for the gamma subtype of the peroxisome proliferator‐activated receptor. Although troglitazone, another drug in this class, displayed unacceptable hepatotoxicity, PIO was approved for human use by the U.S. Food and Drug Administration. To our knowledge, there are no published reports on the genotoxicity of PIO; however, the package insert indicates that it has minimal genotoxicity. In this study, we used the comet assay to investigate the DNA damage in the peripheral blood and liver cells of rats treated with PIO. Sixteen male Sprague‐Dawley rats were randomly distributed into four groups, and dosed daily for 14 days by oral gavage with 0, 10, 20, and 40 mg/kg/day PIO. A dose‐dependent increase in DNA damage, as assessed by % tail DNA, was observed in both hepatocytes and blood lymphocytes of the PIO‐treated groups, with significant increases detected between the rats treated with all the doses of PIO and the control, and between the rats treated with different PIO doses (P < 0.005 to P < 0.0001). Treating nuclei from the exposed animals with an enzyme cocktail containing Fpg and Endonuclease III prior to performing the comet assay increased the level of DNA damage, which reflects oxidized purine and pyrimidine. Taken together, our data indicate that PIO is able to dose‐dependently induce DNA damage in both the liver and blood lymphocytes of rats, which is partially due to the generation of oxidative lesions. Environ. Mol. Mutagen., 2008.

Leptin levels in Henoch–Schönlein purpura

The objective of this paper is to assess the possible role of nitric oxide (NO) and leptin in Henoch–Schönlein purpura (HSP). We investigated the serum leptin and total nitrite levels in 22 children with HSP in the acute phase and after remission and in 20 age- and sex-matched healthy control. Serum leptin levels (nanograms per milliliter; median, min–max) were statistically higher in the acute phase (12.9, 9.1–19.5) than those in the remission phase (6.1, 3.7–10.5, p<0.001) and in the control group (4.9, 3.8–7.5, p<0.001). Also, serum nitrite levels (micromole per liter; median, min–max) were higher in children in the acute phase (45.0, 32.0–60.0) compared to those in remission phase (30.5, 23.0–48.0) and in the control group (29.5, 18.0–38.0) (p<0.001, p<0.001, respectively). There was a positive correlation between serum leptin and total nitrite levels (r=0.65, p<0.001). We have demonstrated that serum leptin and NO levels were increased during the acute phase in children with HSP, and returned to normal levels in remission. We suggest that leptin and NO may have a role in the immunoinflammatory process of HSP, especially in the acute phase. Further studies are needed to clearly establish the roles of leptin and NO in the pathogenesis of HSP.

Adiponectin and resistin concentrations after glucose load in adolescents with polycystic ovary syndrome

Our aims were to evaluate the serum adiponectin and resistin levels at fasting and after glucose load and their interaction with risk of cardiovascular disease (CVD) in adolescents with polycystic ovary syndrome (PCOS). Twenty-two adolescents with PCOS and 16 healthy controls were included in the study. Oral glucose tolerance test (OGTT) was performed in all adolescents. Fasting lipids was measured. Insulin, glucose, adiponectin, and resistin levels were measured at 0 and 120 min of OGTT. Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), fasting glucose-to-insulin ratio (FGIR), and the whole -body insulin sensitivity index (ISI) were calculated. Fasting adiponectin was correlated with ISI (r = 0.729, p < 0.0001), FGIR (r = 0.696, p < 0.0001), QUICKI (r = 0.592, p = 0.004) and HDL-C (r = 0.516, p = 0.028), systolic blood pressure (r = −0.732, p < 0.0001), body mass index (r = −0.738, p < 0.0001), waist circumference (r = −0.706, p < 0.0001), and HOMA-IR (r = −0.595, p = 0.003). No correlation was found between resistin and insulin resistance indexes. Obese adolescents with PCOS have increased CVD risk such as dyslipidemia, hypertension, and insulin resistance than normo-weight PCOS. Hypoadiponectinaemia could be increase risks levels in obese girls with PCOS.

Protein Z and natural anticoagulants in children on peritoneal dialysis and hemodialysis.

Hemostatic alterations due to abnormalities in the coagulation and fibrinolytic system may occur in dialysis patients. Protein Z (PZ) is a vitamin K-dependent coagulation protein promoting assembly of thrombin with phospholipid vesicles. The aim of this study was to investigate PZ and natural anticoagulants in children on hemodialysis (HD) and peritoneal dialysis (PD). Protein Z, protein C (PC), protein S (PS), antithrombin III (AT III), and fibrinogen levels were studied in 24 PD, 13 HD patients and 23 controls. Plasma PZ levels in patients on HD were significantly higher than those on PD and control group (p = 0.04, p = 0.03). We observed elevated PC, PS and AT III activities in children on PD when compared to controls (p = 0.011, p = 0.003, p < 0.001). In HD patients, only PS activity was increased compared to controls (p = 0.016). PC and PS activities did not differ between PD and HD patients whereas AT III activity was higher in PD patients compared to HD patients (p < 0.001). Normal/high levels of PC, PS and AT III suggest that children on PD or HD treatment do not seem to have an increased risk of thrombogenesis due to reduction of these proteins. Increased PZ levels, however, might contribute to the hemostatic alterations in children on HD treatment along with other well known abnormalities.