Orhan Deger

Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments

BACKGROUND Reactive oxygen species (ROS) may play a role in some neuropsychiatric disorders. There is some evidence that the activation of immune-inflammatory process, increase of monoamines catabolism, and abnormalities in lipid compounds may cause overproduction of ROS and, in turn, antioxidative enzyme activities (AEAs) and lipid peroxidation (LP), and that these phenomena may be related to pathophysiology of major depression. METHODS The aims of this study were (i) to examine the AEAs and LP levels of the major depressed (MD) patients, and to compare these with healthy controls; and (ii) to investigate the effect of subchronic treatment with selective serotonin reuptake inhibitors (SSRIs) on AEAs and LP levels in MD subjects. Thirty MD patients, and 32 healthy controls (HC) participated in this study. AEAs and LP levels were determined by measuring several antioxidative enzymes and malondialdehyde (MDA) levels in plasma and/or in red blood cells. RESULTS Major depressed patients, especially melancholic patients, had higher AEA and LP levels than those of healthy controls. After treatment for 3 months with SSRIs, AEA and LP levels of the patients were significantly decreased to normal levels. CONCLUSION These findings suggest that (i) major depression, especially with melancholia, is associated with elevated AEAs and LP, and that (ii) subchronic treatment with SSRIs may have a suppressive effect on AEA and LP. CLINICAL IMPLICATION AND LIMITATION: AEAs might be used for monitoring SSRIs effects.

Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder

BACKGROUND The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial. METHODS Patients with a primary DSM-IV diagnosis of ADHD (N=400; 72 girls, 328 boys, mean age=9.61+/-1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n=202) (150 mg/day) or placebo (n=198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values. RESULTS Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well tolerated and associated with a low rate of side effect. CONCLUSIONS Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels.

Prevalence of prehypertension and hypertension and associated risk factors among Turkish adults: Trabzon Hypertension Study

BACKGROUND To estimate the prevalence, awareness and control of prehypertension (preHT) and hypertension (HT) as defined by JNC-7 criteria in the Trabzon Region and its associations with demographic factors (age, sex, obesity, marital status, reproductive history in women and level of education), socioeconomic factors (household income and occupation), family history of selected medical conditions (diabetes, hypertension, obesity and cardiovascular disease), lifestyle factors (smoking habits, physical activity and alcohol consumption) in the adult population. METHODS In this cross-sectional survey, a sample of households was systematically selected from the central province of Trabzon and its nine towns. A total of 4809 adult subjects (2601 women and 2208 men) were included in the study. Demographic and socioeconomic factors, family history of selected medical conditions, and lifestyle factors were obtained for all participants. Systolic blood pressure (BP) and diastolic BP levels were measured for all subjects. The persons included in the questionnaire were invited to the local medical centers for blood examination between 08:00-10:00 following 12 hours of fasting. The levels of serum glucose (FBG), total cholesterol (Total-C), high density cholesterol (HDL-C), low density cholesterol (LDL-C) and triglycerides were measured with autoanalyzer. Definition and classification of HT was performed according to guidelines from the US JNC-7 report. Prevalence, awareness, treatment and control of HT were assessed. RESULTS The prevalences of HT and preHT were 44.0% (46.1% in women and 41.6% in men) and 14.5% (12.6% in women and 16.8% in men), respectively. Overall, only 41% of the hypertensive individuals had been previously diagnosed. Furthermore, 54.5% of the hypertensive subjects were being treated with antihypertensive drugs (AHD), but only 24.3% of treated subjects had their BP adequately controlled. Among all hypertensive subjects (known and newly diagnosed), only 5.43% had their BP under control. The prevalence of HT increased with age, being highest in the 60- to 69-year-old age group (84.4%) but lower again in the 70+ age group. Interestingly, the prevalence was 16.9% in the 20-to 29-year old age group. HT was associated positively with marital status, parity, cessation of cigarette smoking, and negatively with level of education, alcohol consumption, current cigarette use, and physical activity. Multinomial logistic regression analysis revealed that HT were significantly associated with age, male gender, BMI, low education level, nonsmoking, positive family history of selected medical conditions, occupation, and parity. CONCLUSIONS The Trabzon Hypertension Study data indicated that HT is very common and is an important health problem in the adult population of Trabzon. Patients who are unaware of their status and treated uncontrolled hypertensives are at high risk of early cardiovascular morbidity and mortality. To control preHT and HT, effective public health education and urgent precautions are needed. The precautions include serious health education, a well-balanced diet and increasing physical activity.

Blood coagulation and fibrinolysis in patients with hyperthyroidism

Several papers concerning abnormalities of blood coagulation and fibrinolysis during hyperthyroidism, have been published. Increased von Willebrand Factor (vWF) activity and high fibrinogen levels have been reported. However, there is controversy concerning the presence of a hypercoagulable state in hyperthyroidism. We investigated various hemostatic parameters in 41 hyperthyroid patients and compared them to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor- 1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these hemostatic parameters were examined. Compared with control subjects, fibrinogen, factor IX, vWF, AT III and PAI-1 were significantly increased in patients (p<0.05, p<0.0001, p<0.05, p<0.01 and p<0.0001; respectively), whereas factor X and t-PA were decreased (p<0.05). We showed that free T4 (FT3) levels were correlated with factor VIII activity (r=0.35, p<0.05). FT4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. AT III was inversely correlated with factor VII activity (r=−0.48, p<0.01). Protein C and S were correlated with vWF levels (r=0.58, p<0.0001; r=0.55, p<0.0001, respectively). Protein C was inversely correlated with t-PA (r=−0.39, p<0.01). There was a negative correlation between triglycerides, LDL-C and F X (r=−0.45, p<0.05; r=−64, p<0.01, respectively). Mean platelet volume (MPV) was correlated with anti-thyroid peroxidase (TPO) antibodies (in Graves’disease) and F IX activity (r=0.57, p<0.05 and r=0.39, p<0.05; respectively). We found important differences in the coagulatory /fibrinolytic parameters between the hyperthyroid patients and healthy controls. Hyperthyroid patients may experience vascular endothelial dysfunction and decreased fibrinolytic activity in blood. This endothelial activation may represent a situation with a higher thromboembolic potential.

Protein carbonyl levels in serum and gingival crevicular fluid in patients with chronic periodontitis.

OBJECTIVE Evidence reveals the role of reactive oxygen species (ROS) in many pathologies including periodontitis. Protein carbonylation is the most widely used biomarker for oxidative damage to proteins, and reflects cellular damage induced by ROS. In this study protein carbonyl (PC) levels in serum and gingival crevicular fluid (GCF) in patients with chronic periodontitis (CP) was evaluated. MATERIALS AND METHODS Thirty-three patients with CP and 24 healthy controls were included in the study. Following the clinical measurements and samplings, total protein levels in serum and GCF were determined by Bradford method, and serum and GCF PC levels were measured by modified Levine method. RESULTS PC levels in serum and GCF were significantly higher in the CP group compared to the control group (p<0.05). In all subjects, serum and GCF PC levels showed statistically significant positive correlations with all clinical parameters (p<0.05). CONCLUSIONS The results suggest that both systemic and local/periodontal protein carbonylation increase in CP compared to health and that elevated levels of PCs may be a sign of oxidative damage in periodontitis and correlate well with the periodontal status.

Coagulation and fibrinolysis parameters in type 2 diabetic patients with and without diabetic vascular complications.

Objectives: To investigate the markers of endogenous coagulation/fibrinolysis and vascular endothelial cell function, and to assess the relationships between hemostatic parameters and diabetic vascular complications in type 2 diabetic patients. Materials and Methods: Coagulation and fibrinolysis parameters were measured in 92 type 2 diabetic patients (43 male, 49 female, mean age 50.1 ± 13.4 years) with (n = 44) and without (n = 48) vascular diabetic complications, and in 40 nondiabetic healthy subjects (20 male, 20 female, mean age 49.8 ± 15.1 years). Common lipid parameters were also measured. Results: The plasma levels of fibrinogen, antithrombin III (AT III), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF) activity and prothrombin time were found to be significantly increased in the type 2 diabetic patients compared with the healthy subjects. Glycosylated hemoglobin lc was inversely correlated with plasma protein S and activated prothrombin time. Protein C and S activities were positively correlated with plasma vWF activity, and were negatively correlated with plasma t-PA levels. vWF activity was negatively correlated with plasma t-PA levels. AT III levels were positively correlated with plasma total cholesterol levels, plasma low density lipoprotein cholesterol levels, plasma triglycerides and D-dimer levels. Plasma PAI-1 levels and factor V activity in diabetic patients with microvascular complications were significantly higher than those of the diabetic patients without microvascular complications. The plasma PAI-1 and platelet count were increased in patients with diabetic retinopathy compared with the diabetic patients without retinopathy. Plasma PAI-1 levels and factor VII activity were significantly higher in the diabetic patients with nephropathy than in diabetic patients without nephropathy. Plasma concentrations of fibrinogen and PAI-1 were significantly higher in the diabetic patients with neuropathy than the diabetic patients without neuropathy. Conclusions: The data demonstrated that patients with type 2 diabetes mellitus had a hypercoagulable state and hypofibrinolysis, thereby indicating that activation of coagulation with a reduced fibrinolytic activity may contribute to the increased risk of vascular disease in type 2 diabetic patients.

Prevalence of diabetes, obesity and hypertension in a Turkish population (Trabzon city).

OBJECTIVE The objectives of this study were to determine the prevalence of diabetes mellitus in Trabzon city, Turkey, using standardized diagnostic criteria, and to evaluate associated factors. METHODS A total of 3000 eligible study subjects were selected. Of those, 2646 subjects participated in the study. Individuals aged > or =20 years were selected from their family health cards and were invited to the health station. Anthropometric and demographic data were obtained for each subject. Plasma glucose was measured by an autoanalyser. People without previously diagnosed diabetes were categorized according to WHO diagnostic criteria as follows. Diabetes: a fasting plasma glucose (FPG)> or =140 mg/dl or 2-h plasma glucose > or =200 mg/dl after a 75-g oral glucose load. RESULTS The overall prevalence of diabetes in those > or =20 years of age was 6.0% (n=160). Among diabetic subjects, 69 were newly diagnosed diabetes mellitus. Age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and FPG were higher in diabetic subjects than in non-diabetic subjects. The prevalence of diabetes showed significant association with increased age (P<0.0001). The overall prevalence of obesity was 19.2%. The combined prevalence of both overweight and obesity was 60.6%. The prevalence of obesity was 27.4% among women and 10.7% among men (P<0.0001). Prevalence of diabetes increased with degree of obesity (P<0.0001). The rate of obesity in diabetic subjects was 35.6%. In the study population as a whole, the prevalence of obesity increased with age, being highest in the 50-59 years age group, but lower again in the 60+ age group. Prevalence of SBP> or =140 mmHg was 12.0% and of DBP> or =90 mmHg was 8.2%.

Relationship between lipid peroxidation and disease activity in patients with Behçet's disease.

Behçets disease is a chronic multi-systemic disorder which is characterized by a relapsing systemic inflammatory process. The alteration of lipid profile and lipid peroxidation resulting from the inflammatory process may he associated with an increased risk for atherosclerosis in patients with Behcets disease. We investigated lipids, lipoprotein and lipid peroxidation and their inter-relationships considering the disease activity. Eighteen patients (11 male and 7 female) and 20 age-matched healthy subjects (10 male and 10 female) were studied. Lipid profile including total cholesterol, triacylglycerol, HDL-cholesterol, LDL-cholesterol, lipoprotein(a), apoAI and apoB, and acute phase reactants including polymorphonuclear (PMN) elastase, PMN leukocyte count, erythrocyte sedimentation rate (ESR) and complements (C3, C4) were evaluated in patients in active and inactive periods of Behçets disease and control subjects. The levels of thiobarbituric acid reactive substance (TBARS) were assessed as an indicator of lipid peroxidation. Lipid peroxidation was found to he increased in the active period compared to the inactive period of the disease and control subjects. Also, lipid peroxidation showed correlations of various degrees with atherogenic lipid parameters in both periods of the followed-up patients. In conclusion, patients with Behçets disease in the active period may be much more susceptible to atherogenic events than those in the inactive period of the disease and control subjects.

Effect of Turkish propolis extracts on proteome of prostate cancer cell line

BackgroundPropolis is a natural, resinous hive product that has several pharmacological activities. Its composition varies depending on the vegetation, climate, season and environmental conditions of the area from where it was collected. Surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) is a proteomic approach which has been used in cancer proteomics studies. Prostate cancer is one of the most commonly diagnosed cancers in men. It has shown that nutritional supplements rich in polyphenolic compounds such as propolis play a significant role in prostate cancer chemoprevention. The aim of this study is to evaluate if protein expression profile in PC-3 prostate cancer cell lines could be differentiated when incubated with dimethyl sulfoxide and water extracts of Turkish propolis.ResultsThe antioxidant potentials of dimethyl sulfoxide and water extracts of propolis were found in correlation with the amount of total phenolic compounds of them. Dimethyl sulfoxide and water extracts of propolis of 20 μg/mL reduced the cell viability to 24.5% and 17.7%, respectively. Statistically significant discriminatory peaks between control PC-3 cells and dimethyl sulfoxide extract of propolis-treated PC-3 cells were found to be the proteomic features at m/z 5143, 8703, 12661, 20184 and 32794, detected by CM10 ProteinChip, and the peak at m/z 3772, detected by Q10 ProteinChip. Between control PC-3 cells and water extract of propolis-treated PC-3 cells, statistically significant discriminatory peaks were found to be the proteomic features at m/z 15846, 16052 and 24658, detected by CM10 ProteinChip and the peaks at m/z 10348, 10899 and 11603, detected by Q10 ProteinChip.ConclusionsIt was concluded that dimethyl sulfoxide and water extracts of Turkish propolis may have anti-proliferative activity through differentiating protein expression profile in PC-3 prostate cancer cell lines along with their antioxidant capacity.

Decreased neutrophil antioxidative enzyme activities and increased lipid peroxidation in hyperlipoproteinemic human subjects.

Neutrophils have the capacity to produce free radicals. Free radicals are associated with hyperlipoproteinemia and atherosclerotic processes. For this reason, neutrophil superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), catalase (Cat) activities and thiobarbituric acid reactive substances (TBARS), as an index of lipid peroxidation, have been studied in hyperlipoproteinemic (HLP) and age-matched normolipidemic groups. Lipid parameters including triglycerides, total cholesterol, plasma TBARS, HDL-cholesterol, LDL-cholesterol, apo A-I, apo B have also been determined. Forty subjects (females 18, males 22) with HLP (mean age 43.8+/-8.7 (S.D.)) and 40 normolipoproteinemic subjects (females 17, males 23; mean age 46.4+/-11) were included in the study. Neutrophils were isolated by Percoll gradient centrifugation from venous blood samples. Methods used were as follows: INT method for SOD, UV method at 340 nm based on oxidation of NADPH for GSH-Px and GR, UV method at 240 nm based on degradation of hydrogen peroxide for catalase, and a method based on reaction with thiobarbituric acid for TBARS. Neutrophil SOD, GSH-Px, and catalase activities were found to be significantly low in the hyperlipoproteinemic group compared with the normolipoproteinemic group. GR activity did not differ between both groups. The mean TBARS level in the neutrophil fraction was found to be significantly higher in hyperlipoproteinemics than in that of the normolipoproteinemics. It was concluded that decreased neutrophil antioxidant enzyme activities in hyperlipoproteinemics may lead to insufficient detoxification of free radicals produced in these cells and contribute to increased lipid peroxidation.