Elif Ozerol

Antioxidant enzyme activities and oxidative stress in affective disorders

Recent data from several reports indicate that free radicals are involved in the biochemical mechanisms underlying neuropsychiatric disorders in human. The results of several reports suggest that lower antioxidant defences against lipid peroxidation exist in patients with depression and that there is a therapeutic benefit from antioxidant supplementation in unstable manic-depressive patients. We investigated the antioxidant enzyme status and the indices of oxidative stress and lipid peroxidation end products in erythrocytes from patients with affective disorder. For this purpose, we measured superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, as well as malondialdehyde (MDA) and nitric oxide (NO) levels in patients with affective disorders (n=30) in both pre- and post-treatment periods, and in a control group (n=21). CAT activities were significantly decreased in both pre-, and post-treatment periods in patients compared to the control group. GSH-Px activity in the pre-treatment period in the patients was significantly lower than both post-treatment patient and control groups. MDA levels were increased in both pre-, and post-treatment patient groups compared to the control group. NO level was lower in the pre-treatment patient group than in the control group. There were statistically significant correlations between SOD and MDA, and SOD and NO in the pre-treatment patient and control groups. Because the overall study sample was small, and the post-treatment patient group was even smaller, it can tentatively be suggested that the antioxidant system is impaired during a mood episode in patients with affective disorders, normalizing at the end of the episode.

Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid

Homocysteine (HMC) is a sulfur containing amino acid, which plays a role in methionine metabolism. Folic acid (FA) and vitamin B12 (B12) are essential for remethylization of HMC to methionine. HMC level increases in the deficiency of these vitamins. Hyperhomocysteinemia causes vascular endothelial damage, which causes atherosclerosis. The aim of this study is to investigate the effect of valproate (VA) and carbamazepine (CBZ) on the serum levels of HMC, B12, and FA.Thirty-six children receiving CBZ and 30 children receiving VA for epilepsy for the last 1-year period and 29 healthy children as control were the population of this study. After 6 h of fasting serum HMC, B12, and FA levels were measured and results were compared statistically. Mean values of HMC, FA, and B12 levels in control group were 9.2+/-2.7 micromol/l, 9.0+/-2.0 ng/ml, and 342+/-162 pg/ml, in VA group 14.0+/-6.8 micromol/l, 7.3+/-2.9 ng/ml, and 368+/-159 pg/ml, in CBZ group 16.0+/-13.1 micromol/l, 7.5+/-3.3 ng/ml, and 285+/-158 pg/ml, respectively. Serum HMC levels were higher in VA and CBZ groups than control group (P<0.01 and P<0.05, respectively). Serum FA levels were lower in VA and CBZ groups compared to control group (P<0.05). Serum levels of B12 were not different between VA and control groups (P>0.05). In CBZ group serum B12 levels were lower than control group (P<0.05).FA may be added to the treatment protocol (if the patients take only CBZ, then B12 should also be added) for patients taking these antiepileptic drugs to decrease the degenerative effect of VA and CBZ on vascular endothelium.

Serum leptin concentration is increased in patients with Behçet's syndrome and is correlated with disease activity

Summary Background Behçets syndrome is a systemic, relapsing immuno‐inflammatory disease with a generalized vasculitis of the microvasculature endothelial dysfunction. Leptin, a recently discovered neuroendocrine hormone, is a metabolic peptide that appears to be involved. Serum proinflammatory cytokines upregulate leptin levels and leptin itself directly induces nitric oxide production from endothelial cells with its specific receptors.

Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age-related macular degeneration

Background: Nitric oxide (NO), hydroxyl radical (OH.), superoxide anion (O2−) and hydrogen peroxide (H2O2) are free-radicals released in oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT) are antioxidant enzymes, mediating defense against oxidative stress. Excess NO and/or defective antioxidants cause lipid peroxidation, cellular dysfunction and death. Age-related maculopathy (ARM) or degeneration (ARMD) is the leading cause of irreversible blindness in developed countries. The etiology is unclear and the molecular factors contributing this disease remain to be specified. Aims: This multicenter, double-blind, cross-sectional study aimed to investigate plasma NO and lipid peroxidation levels with relation to antioxidant enzyme activities in erythrocyte and plasma of patients with ARMD compared with healthy control subjects. Methods: NO, lipid peroxidation (measured as plasma malondialdehyde [MDA] levels) and the catalytic activity of SOD, GSHPx and CAT were measured in a group of 41 patients with maculopathy (19 men, 22 women; 67.12 ± 3.70 years) and compared with 25 age- and sex-matched healthy control subjects without maculopathy (12 men, 13 women; 68.04 ± 3.02 years). NO and MDA levels were measured in plasma, CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Color fundus photographs were used to assess the presence of maculopathy, and the patients were divided into two groups using clinical examination and grading of photographs; early-ARM (n = 22) and late-ARMD (n = 19). Results: All patients with maculopathy had significantly (p<0.001) higher plasma NO levels over control subjects (mean ± SD, 48.58 ± 8.81 vs. 28.22 ± 3.39 μmol/l). Plasma MDA levels in patients and control subjects were 4.99 ± 1.00 and 2.16 ± 0.24 μmol/l, respectively, and the difference was significant (p<0.001). On the other hand, SOD and GSHPx activities were significantly lower in both RBCs and plasma of patients with maculopathy than in control subjects (RBCs-SOD, 3509.30 ± 478.22 vs. 5033.30 ± 363.98 U/g Hb, p<0.001; plasma-SOD, 560.95 ± 52.52 vs. 704.76 ± 24.59 U/g protein, p<.001; RBCs-GSHPx, 663.43 ± 41.74 vs. 748.80 ± 25.50 U/g Hb, p<0.001; plasma-GSHPx, 98.26 ± 15.67 vs. 131.80 ± 8.73 U/g protein, p<0.001). RBCs-CAT levels were not different between groups (131.68 ± 12.89 vs. 133.00 ± 13.29 k/g Hb, p=0.811). Late-ARMD patients had significantly lower antioxidant enzyme levels and higher MDA levels when compared with early-ARM patients (for each, p<0.001). In addition, plasma NO and MDA levels were negatively correlated with SOD and GSHPx activities. Conclusions: This study demonstrated for the first time that NO, the most abundant free-radical in the body, might be implicated in the pathophysiology of ARMD in association with decreased antioxidant enzymes and increased lipid peroxidation status.

Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behçet's disease.

Background/aims: Behçets disease (BD) is a systemic inflammatory vasculitis of young adults with unknown aetiology, characterised by endothelial dysfunction and occlusion in both deep venous and retinal circulation. Ocular involvement occurs in 70% of cases and is characterised by periphlebitis, periarteritis, vascular occlusion, and thrombosis leading to blindness despite vigorous treatment. Endothelin-1 (ET-1) is a vasoconstricting peptide while nitric oxide (NO) is a relaxing molecule and both are released by endothelium for blood flow regulation. Homocysteinaemia is a newly defined term connected to the increased risk of atherothrombotic and atherosclerotic systemic and retinal vascular occlusive diseases, and its role in the course of BD has not been previously described. The authors aimed to detect serum total homocysteine (tHcy), ET-1, and NO in BD and to assess if tHcy, ET-1, and NO are associated with ocular BD or disease activity. Methods: 43 consecutive patients with ocular (n = 27) or non-ocular (n = 16) BD (36.95 (SD 9.80) years, 22 male, 21 female) satisfying international criteria, and 25 age and sex matched healthy control subjects (37.88 (8.73) years, 13 male, 12 female) without a history of systemic or retinal venous thrombosis were included in this study. Patients were examined by two ophthalmologists with an interest in BD. Serum tHcy, ET-1, and NO concentrations were measured in both groups. Hyperhomocysteinaemia was defined as a tHcy level above the 95th percentile in the control group. Patients were divided into active and inactive period by acute phase reactants including α1 antitrypsin, α2 macroglobulin, erythrocyte sedimentation rate, and neutrophil count. Results: The overall mean serum tHcy, ET-1, and NO levels were significantly higher in patients with BD than in control subjects (tHcy = 15.83 (4.44) v 7.96 (2.66) ng/ml, p <0.001; ET-1 = 17.47 (4.33) v 5.74 (2.34) μmol/ml, p <0.001; NO = 37.60 (10.31) v 27.08 (7.76) μmol/l, p <0.001). Serum tHcy, ET-1, and NO levels were significantly higher in active patients than in inactive patients and control subjects. In addition, among patients with ocular BD, the mean tHcy levels were significantly increased and correlated with ET-1 and NO levels when compared with non-ocular disease and control subjects. All acute phase reactant levels were significantly higher in active period than in inactive stage and controls. Conclusions: Elevated tHcy may be responsible for the endothelial damage in BD and may be an additional risk factor for the development of retinal vascular occlusive disease, contributing to the poor visual outcome in these patients. Assessment of tHcy may be important in the investigation and management of patients with BD, especially with ocular disease.

Effect of Smoking on Serum Concentrations of Total Homocysteine, Folate, Vitamin B12, and Nitric Oxide in Pregnancy: A Preliminary Study

Objective: Nitric oxide (NO) is a potent vasodilator released by endothelial cells that plays an important role in modulating maternal and fetal vascular tone in normal pregnancy. Lower plasma levels of vitamins may result in hyperhomocysteinemia, a known risk factor in pregnancy. The aim of this study was to investigate whether there are alterations in the serum levels of total homocysteine (tHcy), folate, vitamin B12, and total nitrite, as an index of NO, in smoking as compared with age-matched nonsmoking pregnant women. Methods: Thirty-three women (19 smoking and 14 nonsmoking) between 16 and 22 weeks of their gestation were included in this study. The serum tHcy levels were analyzed by using an enzyme-linked immunosorbent assay kit. Vitamin B12 and folate values were measured by means of DPC kits. Total nitrite was measured by Griess reaction as an index of endogenous NO production. Results: The serum tHcy concentrations were significantly increased in smoking as compared with nonsmoking pregnant women (p < 0.001). The folate and vitamin B12 concentrations were lower in smoking than in nonsmoking pregnant women, but only the differences in folate concentrations were statistically significant (p < 0.001). The tHcy concentrations showed a significant negative correlation with folate in the smoking pregnant women. The serum total nitrite concentrations were lower in smoking than in nonsmoking pregnant women (p < 0.05). In addition, the serum nitrite levels in smoking pregnant women had significant negative correlations with tHcy and positive correlations with folate and vitamin B12 levels. Conclusions: In the light of our findings, we propose that smoking might enhance the vasoconstrictor capacity in pregnant women by increased tHcy concentrations and by a simultaneous decrease in the production of NO which is a vasodilator compound.

Use of caffeic acid phenethyl ester to prevent sodium-selenite-induced cataract in rat eyes

Purpose: To investigate whether caffeic acid phenethyl ester (CAPE) prevents sodium‐selenite‐induced cataract. Setting: Department of Ophthalmology and Biochemistry, Inonu University Medical Faculty, Turgut Ozal Medical Center, Research Hospital, Malatya, Turkey. Methods: Sixty Spraque‐Dawley rat litters were randomized into 3 groups. In Group 1 (n = 18), sodium selenite (30 nmol/g body weight) was injected subcutaneously on postpartum day 10. In Group 2 (n = 22), subcutaneous CAPE (15 &mgr;mol/kg) and sodium selenite (30 nmol/g body weight) were injected on postpartum day 10. The CAPE dose was continued subcutaneously for 3 days after the initial injection. Only subcutaneous saline was injected in Group 3 (control, n = 20). The development of cataract was assessed weekly, and its density was graded by slitlamp biomicroscopy and photography. Removed rat lenses were analyzed for glutathione (GSH) and malondialdehyde (MDA, marker of lipid peroxidation). Results: Group 2 rats had clear lenses or minor cataract. All Group 1 rats developed more severe cataract or complete opacification. The between‐group difference was statistically significant (P < .05). All control lenses (Group 3) were clear. The mean GSH level in Group 1 (4.49 &mgr;mol/g wet weight ± 0.93 [SD]) was significantly lower than that in Group 2 (8.63 ± 0.88 &mgr;mol/g wet weight) (P < .05) and controls (10.76 ± 1.97 &mgr;mol/g wet weight) (P < .05). The mean MDA level in Group 1 (8.54 ± 1.31 nmol/g wet weight) was significantly higher than that in Group 2 (5.23 ± 0.84 nmol/g wet weight) (P < .05) and controls (4.19 ± 0.81 nmol/g wet weight) (P < .05). Conclusion: Caffeic acid phenethyl ester effectively suppressed cataract formation in rats. The protective effect was supported by lower GSH and higher MDA levels in Group 1 than in Group 2, suggesting the antioxidant efficacy of this agent. Since CAPE has no known harmful effect on normal cells, it may be beneficial in clinical use in humans.

Effect of long-term therapy with sodium valproate on nail and serum trace element status in epileptic children

Antiepileptic drugs could cause changes in the trace element status of the body. Valproic acid (VPA) is a very effective anticonvulsant agent widely used in the management of various forms of epilepsy. Nail trace element content is a reliable index of trace element nutritional status of the body. To determine whether some of the side effects of antiepileptic drugs could be the result of zinc (Zn) depletion within tissues, Zn concentrations as well as copper (Cu) concentrations in nail and serum in 59 children having various types of epilepsy receiving valproate and 31 controls were assessed. Although serum Zn level in epileptic patients was found to be decreased, there was no difference in nail samples when compared to controls. There was a statistically significant increase in nail Cu level in epileptic patients when compared to controls. On the other hand, serum Cu levels were not different between the groups. Although none of our patients showed any symptoms of Cu elevation and Zn depletion, we should pay attention to potential body trace element changes in patients with epilepsy under VPA treatment. In conclusion, our results indicate that serum trace metal homeostasis might be affected by VPA therapy, but not by the convulsive disorder itself.

Adrenomedullin and Leptin Levels in Diabetic Retinopathy and Retinal Diseases

Purpose: Proliferative and vascular retinal diseases are important cause of irreversible blindness. Consistent features of these diseases are endothelial dysfunction and angiogenesis. Adrenomedullin (ADM) is a multifunctional vasorelaxant peptide. Leptin is a recently discovered metabolic peptide that regulates energy metabolism in human. In the present study, we aimed to investigate the possible roles of adrenomedullin and leptin in the pathophysiology of diabetic and proliferative diseases. Methods: Ten patients with proliferative diabetic retinopathy (57.1 years, 5 female and 5 male) and 8 patients (51 years, 5 female and 3 male) with other retinal diseases including macular hole and epiretinal membrane were included in this study. All the patients had undergone pars plana vitrectomy for complications of the diseases. Vitreous samples were collected by vitreous tap during the vitrectomy. Adrenomedullin analysis was made by using reverse-phase high-performance liquid chromatography (HPLC). Leptin was measured by enzyme-linked immunosorbent assay (ELISA). Body mass index (BMI) [weight (kg)/height (m2)] was calculated for each group. The Mann-Whitney U test was used for statistics. Results: The age, gender ratio and BMI were not substantially different between the two groups. The mean vitreous adrenomedullin levels (63.9 ± 7.1 pmol/l) were significantly higher (p < 0.05) in group I than in group II (34.25 ± 3.0 pmol/l). Leptin levels in vitreous (4.54 ±1.6 ng/ml) were also significantly higher (p < 0.05) in patients with diabetic retinopathy than in those without diabetes (1.83 ± 0.5 ng/ml). Conclusion: Increased adrenomedullin and leptin levels in vitreous humor might be a possible newly associated factor in the course of vascular and proliferative retinal diseases.

The comparison of nail and serum trace elements in patients with epilepsy and healthy subjects.

The objective of this prospective study was to determine the levels of manganese (Mn), copper (Cu), and zinc (Zn) levels in both nail and serum from patients with epilepsy. For this purpose, levels of these elements were measured in 31 patients with epilepsy and 19 healthy subjects. Element analyses were carried out by atomic absorption spectrophotometer (AAS). Increased Mn levels were detected in nail of patients with epilepsy compared to healthy controls (P<.008). The main nail Zn and Cu levels were found to be unchanged in epileptic patients compared to control subjects. There were no significant differences in serum Mn and Zn levels between epileptic patients and control subjects. However, there was a statistically significant increase in serum Cu levels in patients with epilepsy in comparison with control group (P<.009). Our results demonstrate that some trace element levels may vary in epileptic patients, and because of the more stable status, the analysis of these element levels in some tissues such as nail might be superior to serum analysis.