Hüsamettin Erdamar

Carotid intima–media thickness in patients with cardiac syndrome X and its association with high circulating levels of asymmetric dimethylarginine

BACKGROUND The cause of myocardial ischemia and chest pain in patients with cardiac syndrome X (CSX) has been explained by mechanisms including endothelial dysfunction. CSX patients have higher levels of asymmetric dimethylarginine (ADMA) and increased mean common carotid intima-media thickness (C-IMT). Accordingly, this study was designed to examine C-IMT with its association serum endothelial function parameters in patients with CSX. METHODS The study population consisted of 30 enrolled consecutive patients with diagnosis of CSX. As a control group, 30 individuals with the complaint of anginal chest pain without any ischemia on myocardial perfusion scintigraphy and with normal coronary angiographies were selected. C-IMT was measured by recording ultrasonographic images of both the left and the right common carotid artery. Plasma levels of L-arginine, ADMA, and nitrate/nitrite (NO(x)) were measured from blood samples. RESULTS Both C-IMT (mm) and carotid atherosclerotic plaques were significantly higher in patients with CSX than in control group. Also, the plasma level of NO(x), L-arginine, and L-arginine/ADMA ratio were lower in patients with CSX than they were in the control group subjects. Plasma ADMA level increased in the CSX patients group. Correlation analysis showed significant positive correlation with C-IMT and plasma ADMA levels and showed significant negative correlation with plasma NO(x) and L-arginine levels. L-arginine/ADMA ratio and C-IMT was also showed significant negative correlation with the same analysis. CONCLUSIONS CSX patients had higher plasma ADMA levels and C-IMT values than the controls, reflecting the presence of subclinical atherosclerosis. These findings suggest that, besides endothelial dysfunction, presence of atherosclerosis may also contribute to the etiopathogenesis of the CSX phenomenon.

The effect of nebivolol treatment on oxidative stress and antioxidant status in patients with cardiac syndrome-x

BackgroundFree radical-mediated oxidative stress has been implicated in the etiopathogenesis of several disorders. The aim of this study was to elucidate the effect of treatment with nebivolol on the metabolic state of oxidative stress, and antioxidant status markers in patients with cardiac syndrome-X (CSX), additionally, to compare with the effect of metoprolol treatment. MethodsThirty patients, 17 female and 13 male, with CSX were enrolled in the study. Nebivolol (5 mg/day) or metoprolol (50 mg/day) was administrated for 12 weeks. Twelve hour fasting blood samples, taken at the initiation and on the third month of therapy, were analyzed for the levels of malondialdehyde (MDA), nitrite+nitrate (NOx), and the activity of myeloperoxidase (MPO), superoxide dismutase (SOD). No patient presented additional risk factors for increased reactive oxygen species levels. ResultsCompared with sixteen control participants, patients with CSX had significantly higher activity of MPO and levels of MDA, but significantly lower SOD activity and levels of NOx before treatment. After treatment, MPO activity and MDA levels were significantly reduced; SOD activity and NOx levels were significantly increased with nebivolol but remained unchanged with metoprolol. ConclusionWe have shown that patients with CSX who taken nebivolol have lower serum MPO activity, levels of MDA and higher serum SOD activity, NOx levels when compared with metoprolol treatment. Exercise stress test parameters were also ameliorated in patients who had taken nebivolol in contrast to metoprolol. Nebivolol treatment may be a novel treatment strategy in cases with CSX in the future.

Immunomodulation of acute experimental spinal cord injury with human immunoglobulin G

Immunomodulation of acute spinal cord injury may inhibit the activity of specific inflammatory cascades and result in recovery of motor function. In this study, evaluation of the protective effect of a well-known anti-inflammatory immunomodulator, immunoglobulin G (IgG), was conducted in rats after a 50 g/cm contusion spinal cord injury. Following injury, 400 mg/kg of IgG was administered to the treatment group. Twenty-four hours later, animals were assessed functionally via an inclined plane and the Basso-Beattie-Bresnahan motor scale and compared to controls. Tissue was reviewed for myeloperoxidase activiy (MPO) and lipid peroxidation (LPO), and electron microscopy was conducted to assess tissue ultrastructure. Significant functional preservation was observed in the IgG treatment group. In addition, biochemical assays revealed decreased MPO activity, and electron microscopic views of tissue showed preserved ultrastructure. IgG treatment following acute contusion injury to the rat spinal cord confers functional and structural neuroprotection.

Protective effect of taurine on respiratory burst activity of polymorphonuclear leukocytes in endotoxemia.

Summary.The aim of this study was to evaluate the effect of endotoxin on PMN leukocyte respiratory burst activity by measuring G6PD, NADPH oxidase and XO activities in guinea pig. In addition, the possible protective role of taurine against endotoxin-mediated PMN leukocyte function was examined. All experiments were performed with four groups (control, taurine, endotoxemia, taurine plus endotoxin) of ten guinea pigs. After the endotoxin was administrated (4 mg/kg) both G6PD and NADPH oxidase activities were significantly reduced compared with the control group. NADPH oxidase activity returned to the control value and G6PD activity also increased but it did not reach the control value. However when taurine was administrated (300 mg/kg) the activity of NADPH oxidase reached the control value; furthermore, G6PD activity also increased but it could not reach to the control value. When taurine was administrated alone, no effect on these enzymes was observed. Following the endotoxin administration, the activity of XO considerably increased. When taurine was administrated together with endotoxine and alone, this activity decreased compared to control value in both conditions. These results indicate that the O2•− formation in PMN leukocytes after the endotoxin administration is ensured by the catalysis of XO due to the inhibited NADPH oxidase activity. It was observed that taurine has considerable anti-inflammatory and antioxidant effects. However, conflicting results were obtained when taurine was administrated alone or together with an oxidant agent.

The effect of taurine on polymorphonuclear leukocyte functions in endotoxemia

Summary.The aim of the present study was to measure MPO activity in PMN leukocytes after endotoxin administration, and to compare the levels of NO2− competing with taurine for reaction with HOCl. Furthermore we aimed to determine TauCl levels, a product of MPO–H2O2–Halide system, and to evaluate anti-inflammatory properties of PMN in endotoxemia. In addition, our second objective was to investigate the effect of taurine, an antioxidant amino acid, on anti-bactericidal and anti-inflammatory functions of PMN after administration of endotoxin together with taurine.All experiments were performed with four groups (control, taurine, endotoxemia, and taurine plus endotoxin) of ten guinea pigs. After endotoxin administration (4 mg/kg), MPO activities increased and taurine levels decreased. Therefore levels of TauCl, NO2•− increased. We observed the effects of taurine as conflicting. When taurine was administrated alone (300 mg/kg), all of these parameters decreased.Consequently, we suggested that taurine is influential in infected subjects but not on healthy ones as an antioxidative amino acid. In addition, we believe that in vivo effects of taurine may differ from those in vitro depending on its dosage.

Increased lipid peroxidation and impaired enzymatic antioxidant defense mechanism in thyroid tissue with multinodular goiter and papillary carcinoma.

OBJECTIVES We aimed to evaluate the oxidant/antioxidant status of thyroid tissue in patients with multinodular goiter, papillary carcinoma and to compare with their nonpathologic tissues. METHODS We studied 41 patients with multinodular goiter who underwent surgical treatment. The patients were divided into three groups according to clinical diagnosis. Malondialdehyde, selenium, total superoxide dismutase and glutathione peroxidase of thyroid tissue samples were determined in 14 toxic multinodular goiters, 18 non-toxic multinodular goiters, and 9 papillary carcinomas. RESULT Superoxide dismutase and glutathione peroxidase and selenium were found lower but malondialdehyde was higher in both nodule and cancerous tissues compared with those of control ones. The level of malondialdehyde in non-toxic multinodular goiters group was higher than toxic multinodular goiters group in nodule tissues. CONCLUSIONS It can be stated that the lipid peroxidation is increased and enzymatic free radical defense system was significantly impaired in patients with both multinodular goiters and papillary carcinomas.

Effects of hyperbaric oxygen on energy production and xanthine oxidase levels in striated muscle tissue of healthy rats

We investigated the effects of hyperbaric oxygen (HBO) treatment on striated muscle tissue in healthy rats. The treatment group of rats (n=16) was given HBO daily on weekdays for 2 h over a 4-week period while a control group (n=8) was not treated. Tissue samples were taken from the left and right vastus lateralis before and after the HBO treatment period, respectively, for all rats in both groups. Levels of adenosine monophosphate (AMP), adenosine diphosphate, andenosine triphosphate (ATP) and xanthine oxidase in the muscle tissue were determined. HBO treatment caused a statistically significant increase in ATP (p=0.001) and decrease in AMP (p=0.02) in the HBO-treated group, while there were no significant differences in metabolites in the control group. These results suggest that HBO treatment induces an increase in the ATP levels of muscle tissue with normal mitochondria. Thus, HBO might have some beneficial effects in the treatment of heteroplasmic mitochondrial disease, where normal and defective mitochondria coexist.

Can Bile Acids Be an Etiological Factor for Laryngeal Carcinoma

Purpose: The objective of this study is to show the accumulation of bile acids in laryngeal tissues of laryngeal carcinoma patients. Materials and Methods: The present study compared the total bile acid level in the hypopharyngeal tissue, tumor tissue, and blood of 21 primary laryngeal carcinoma patients (study group) to that in the hypopharyngeal tissue and blood of 15 patients with benign laryngeal lesions (control group). Results: The total bile acid level was significantly higher in the tumor and hypopharyngeal tissues of the study group than in the hypopharyngeal tissues of the control group; however, the difference in the blood total bile acid level between the 2 groups was not significant. Conclusion: Bile acids in reflux material accumulate in the laryngeal tissue in laryngeal carcinoma patients; therefore, bile acids should be considered a carcinogenic factor in the etiology of laryngeal carcinoma because of their mutagenicity due to DNA breaking, as they cause chronic inflammation due to intracellular accumulation.

The Relationship Between Taurine and 3-Nitrotyrosine Level of Hepatocytes in Experimental Endotoxemia

It has been proposed that taurine may function as an oxidant in a dose-dependent manner in vivo and in vitro. The present study was carried out to investigate the relationship between taurine concentration and 3-nitrotyrosine level, a stable marker of peroxynitrite action, in hepatocytes of guinea pig in endotoxemia before and after taurine administration. The levels of taurine and 3-nitrotyrosine were measured by HPLC method. In the present study, taurine was low concentration in hepatocytes exposed to endotoxemia. In taurine plus endotoxin treated animals, HPLC analysis showed higher taurine level compared with animals only supplemented with taurine. But 3-nitrotyrosine levels were same in both taurine alone and taurine plus endotoxin groups. In conclusion, taurine is able to prevent the damaging effect of peroxynitrite, at concentration measured in hepatocytes, in our experimental conditions.

Cilostazol Attenuates Spinal Cord Ischemia-Reperfusion Injury in Rabbits

OBJECTIVE The aim of this study was to evaluate the pretreatment effect of cilostazol on spinal cord ischemia-reperfusion injury. DESIGN Prospective, interventional study. SETTING Research laboratory, single institution. PARTICIPANTS Twenty-four New Zealand white rabbits. INTERVENTIONS Twenty-four rabbits were divided into 3 equal groups: group I (sham), group II (ischemia-reperfusion, control group), and group III (cilostazol, administered orally 30 mg/kg/day for 3 days before the surgery). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the iliac bifurcation for 30 minutes. Seventy-two hours postoperatively, the motor function of the lower limbs was evaluated in each animal according to the modified Tarlov score. Spinal cord and blood samples were taken for histopathologic and biochemical analyses at the 72nd hour of reperfusion. MEASUREMENTS AND MAIN RESULTS All rabbits in the ischemia-reperfusion group (group II) showed severe neurologic deficits. The median (IQR) Tarlov scores postoperatively at 72 hours in groups I, II, and III were 5.0(-), 2.0(1.0), and 4.5(1.0), respectively. Administration of cilostazol resulted in a significant reduction in motor dysfunction when compared with the ischemia-reperfusion group (p<0.001). In the ischemia-reperfusion group, serum and tissue glutathione peroxidase and superoxide dismutase activity were significantly less compared with the sham group (group I) (p<0.05). Serum and tissue glutathione peroxidase and superoxide dismutase levels in the cilostazol-treated group (group III) were higher compared with the ischemia-reperfusion group (p<0.05). In the cilostazol-treated group, serum and tissue malondialdehyde levels were lower compared with the ischemia-reperfusion group (p<0.05). Histopathologic analysis found decreased neuronal injury in the cilostazol group when compared with the ischemia-reperfusion group (p< 0.05). CONCLUSIONS This study showed that pretreatment with cilostazol significantly ameliorated neurologic functional outcome and attenuated neuronal histopathologic injury after transient aortic occlusion in rabbits.