Kader Köse

Hypoxia-induced necrotizing enterocolitis in the immature rat: The role of lipid peroxidation and management by vitamin E

The authors developed an experimental model of necrotizing enterocolitis (NEC) by hypoxia-reoxygenation, and determined the content of malondialdehyde levels as an index of lipid peroxidation, related with a free-radical reaction in the gastrointestinal tract of newborn rats. They also investigated the role of vitamin E, an antioxidant, in this free-radical injury. The study was performed on 1-day-old rats. The 30 rat pups were divided into three groups. Hypoxia was induced by placing the pups in a 100% carbon dioxide chamber for 5 minutes. The pups were reoxygenated with 100% oxygen for 5 minutes. Group 1 (n = 10) was subjected to hypoxia-reoxygenation and killed 3 days after hypoxia. Group 2 (n = 10) was subjected to hypoxia-reoxygenation and treated with vitamin E (30 IU/kg/d intraperitoneally) for the next 3 days, and killed. Group 3 (n = 10) rats served as controls. The histopathology of the intestinal lesions in group 1 animals was characteristic of ischemic injury and ranged from superficial epithelial damage with villous shortening to transmural necrosis. In the vitamin E-treated animals these lesions were milder. The malondialdehyde levels of group 1 were significantly higher than those of the other two groups (P < .001). This study shows that oxidant-mediated lipid peroxidation injury plays a central role in mediating hypoxia-induced intestinal necrosis and suggests that vitamin E may play a therapeutic role in NEC.

Increased advanced oxidation protein products in Behcet's disease: a new activity marker?

Background  Behçets disease (BD) is a chronic inflammatory disease with unknown pathogenesis. As various functions of neutrophils in peripheral blood, such as chemotaxis, phagocytosis and generation of reactive oxygen species (ROS) increase in BD, ROS‐mediated oxidative stress related to neutrophil activation may have an important role in the pathogenesis of BD.

Lipoperoxidation induced by hydrogen peroxide in human erythrocyte membranes. 2. Comparison of the antioxidant effect of Ginkgo biloba extract (EGb 761) with those of water-soluble and lipid-soluble antioxidants.

An in vitro model using healthy human erythrocyte suspensions was used to compare the antioxidant effect of standardized Ginkgo biloba extract (EGb 761) with those of water-soluble (ascorbic acid, glutathione and uric acid) and lipid-soluble (α-tocopherol and retinol acetate) antioxidants. Lipid peroxidation was induced by hydrogen peroxide in the absence (control) and presence of antioxidants at low (25 μg/ml) and high (250 μg/ml) concentrations. Malondialdehyde production was determined as the indicator of lipid peroxidation during the incubation period. The results suggest that all of the antioxidants, except ascorbic acid, have antioxidant potential in this system in a concentration-dependent manner. When the antioxidants were compared, EGb 761 was found to be more effective than water-soluble antioxidants, and as effective as lipid-soluble antioxidants. Among the lipid-soluble antioxidants there was no significant difference in potency between α-tocopherol and retinol acetate, but uric acid was the most potent of the water-soluble antioxidants. The antioxidant potency of EGb 761 appears to be comparable with that of the well-known antioxidants α-tocopherol and retinol acetate.

The evaluation of lipid peroxidation and adenosine deaminase activity in patients with Behçet's disease.

OBJECTIVE Despite unknown etiology, immunologic alterations and neutrophil hyperfunctions may be involved in the etiopathogenesis of Behçets Disease (BD). The purpose of the study was to investigate whether adenosine deaminase (ADA) activity, accepted as a nonspecific marker of T lymphocyte activation, may have a potential role in BD, and also may be related to the production of reactive oxygen species (ROS) by neutrophils. DESIGN AND METHODS ADA activities and malondialdehyde (MDA; endproduct of lipid peroxidation induced by ROS) levels in both plasma and erythrocytes were spectrophotometrically measured in 25 patients with BD and also in 25 healthy controls. RESULTS ADA activity was found to be higher in plasma, but lower in erythrocytes; plasma and erythrocyte MDA levels were higher in BD patients than those of controls. In addition, plasma ADA activity was positively related to MDA levels in both plasma (p < 0.05) and erythrocytes (p < 0.01). There was also positive correlation between MDA levels (p < 0.05), but negative correlations between ADA activities (p < 0.01) and also between ADA and MDA values in erythrocytes (p < 0.01) of BD patients. CONCLUSION These findings may provide some evidence for a potential role of T lymphocyte activation in BD as reflected by increased plasma ADA activity, and for the presence of possible interrelationship between activated T cells and neutrophil hyperfunctions, such as ROS generation, as reflected by increased MDA levels.

The Effects of Electroconvulsive Therapy on GABAergic Function in Major Depressive Patients

Objectives: It has been proposed that major depression is associated with a dysfunction of the &ggr;-aminobutyric acid (GABA) system. This study was planned to investigate whether there are any alterations in GABAergic activities in major depressive patients and, if there are, whether electroconvulsive therapy (ECT) has any effect on these changes. Methods: Twenty-five depressed inpatients who responded to a course of ECT and 23 healthy subjects were included in the study. Serum GABA levels were measured 2 days before and 10 minutes after the first ECT and 3 days after the last ECT, and a baclofen challenge test was performed 2 days before the first ECT and 3 days after the last ECT in the patients. The same tests were carried out only once in the control group. Results: Depressive patients had lower serum GABA levels compared with healthy individuals, and ECT caused a significant increase in these levels. The acute effect of the one-ECT procedure was a huge increase in the baseline GABA levels. Although there was no difference in the maximum alteration in growth hormone with baclofen between the patients and controls before the therapeutic ECT course, it became significantly higher in the depressive patients than in the controls after the treatment. Conclusions: The findings of this study support the GABA deficit hypothesis of major depression because major depressive patients have lower levels of serum GABA that are increased by a completed ECT course. ECT seems to increase brain GABA levels as well as GABAB activity, and these effects may contribute to its mechanism of therapeutic effect.

Oxidative enzymes of polymorphonuclear leucocytes and plasma fibrinogen, ceruloplasmin, and copper levels in Behcet's disease

This study was performed to investigate the antioxidant mechanisms of polymorphonuclear leucocytes (PMN) in active stage of Behçets Disease. PMN activities of myeloperoxidase (p < 0.02), superoxide dismutase (p < 0.001), catalase (p < 0.005), and glutathione peroxidase (p < 0.005) were significantly lower in the patients: the NADPH oxidase activity was significantly higher (p < 0.001) than those in controls. The plasma levels of ceruloplasmin (Cp), fibrinogen, and copper (Cu) were also significantly higher in the patients group (p < 0.001). Significant and positive correlations were found between the glutathione peroxidase and catalase activities (p < 0.001) and also between the plasma Cp and Cu levels (p < 0.001) in the patients group. However, no correlation was observed among the other enzyme activities. In the control group, a significantly positive correlation was present only between the plasma ceruloplasmin and Cu levels (p < 0.001). It was concluded that (impaired PMN functions) decreased enzyme activities in the antioxidant system and increased levels of oxygen free radicals may play a role in tissue damage in Behçets disease.

Lipoperoxidation Induced by Hydrogen Peroxide in Human Erythrocyte Membranes. 1. Protective Effect of Ginkgo Biloba Extract (EGb 761)

The antioxidant potential of Ginkgo biloba extract (EGb 761) on healthy human erythrocyte membranes was investigated. Lipoperoxidation was induced in erythrocyte suspensions using hydrogen peroxide, in the presence of EGb 761 at 37 °C; malondialdehyde production was determined as the indicator of lipoperoxidation during the incubation period. The results for EGb 761 at concentrations of 0, 25, 50, 125, 250 and 500 μg/ml suggest that the antioxidant potential of EGb 761 in erythrocyte membranes increases with dose. Similarly, using different incubation periods (0, 15, 30, 45 or 60 min) indicated that the antioxidant effect of EGb 761 increased by the incubation time.

Plasma selenium levels in rheumatoid arthritis

The plasma selenium (Se) levels were determined in patients with rheumatoid arthritis (RA) and healthy controls. Plasma Se levels in 60 patients were found to be significantly lower than those in 60 normal, healthy controls (p<0.001). Similar significant differences were determined in sex-matched comparisons between patients and controls (p<0.001) but there was no significant difference in plasma Se levels in sex-matched comparisons in both groups (p>0.05).Our results suggest that Se is an important factor in RA.

Antioxidant potential of propylthiouracil in patients with psoriasis.

OBJECTIVE There is growing evidence supporting the reactive oxygen species (ROS) in the pathogenesis of psoriasis. Propylthiouracil(PTU), an antithyroid drug, has been shown to have beneficial effects on psoriasis. The aim of this study was to investigate both disturbances in oxidant/antioxidant system in psoriasis and whether PTU, shown to have immunomodulatory effects and antioxidant potential, has effects on oxidant/antioxidant system and clinical improvement in psoriatics. DESIGN AND METHODS Malondialdehyde (MDA), end product of lipid peroxidation, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and antioxidant enzymes were measured in plasma, erythrocytes and skin biopsies of psoriatics who were resistant to conventional therapy before and after 8 weeks of oral treatment with PTU (300 mg/day) or PTU/thyroxine (25 microg/day- to prevent possible hypothyroidism). The same parameters were also studied in healthy controls. Psoriasis Area and Severity Index (PASI) scores were used to evaluate the severity of the disease, and routine analyses and thyroid function tests were measured during the study. RESULTS Increased baseline MDA in all samples were found to be lower. In addition baseline SOD and GSH-Px in skin and erythrocytes were also lower. The increased plasma SOD levels in skin and erythrocytes of the study groups was found to be higher and lower,respectively in all patients after the treatment. No tissue parameters or erythrocyte GSH-Px were different from control levels at the end of the study. Significant clinical improvement and decreased PASI scores were observed in all patients. Post treatment TSH levels were higher in all patients, but these levels were within the reference range and none had clinical hypothyroidism. CONCLUSION These findings may provide some evidence for a potential role of increased lipid peroxidation and decreased antioxidant activity in psoriasis. PTU may be considered as treatment model in psoriasis, in particular for resistant cases, because of its antioxidant potential, and also antiproliferative and immunomodulatory effects.

Effect of propylthiouracil on adenosine deaminase activity and thyroid function in patients with psoriasis

Background T‐cell activation has been implicated in the pathogenesis of psoriasis; adenosine deaminase (ADA) activity has been considered as a marker of T‐cell activation. The antithyroid drug propylthiouracil (PTU) has recently been shown to have beneficial effects on psoriatic lesions, probably by acting on the immune system.