Birgül Vanizor

The evaluation of autoantibodies against oxidatively modified low-density lipoprotein (LDL), susceptibility of LDL to oxidation, serum lipids and lipid hydroperoxide levels, total antioxidant status, antioxidant enzyme activities, and endothelial dysfunction in patients with Behçet’s disease

OBJECTIVES Behçets disease is a multisystem disorder characterized by a chronic inflammation including acute attacks and remission periods. Decreased enzyme activity of the antioxidant system and increased levels of free radicals may have important roles in the damage of tissues observed in the disease period. In addition, the atherogenic tendency of serum lipid, lipoproteins, lipid peroxidation levels and endothelial dysfunction accompany the above mentioned findings. As a consequence of these events, different degrees of low density lipoprotein (LDL) oxidation occur in vivo, and then autoantibodies against oxidized-LDL(AuAb-oxLDL) are produced. DESIGN AND METHODS Lipids, lipoproteins, lipid hydroperoxide, AuAb-oxLDL, total antioxidant status (TAS), serum-soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor 1 (PAI-1) levels in serum, the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes and plasma, were determined in 25 patients with Behçets disease and in 25 healthy volunteers. Also, susceptibility to copper-induced in vitro oxidation of LDL by using lag time, a measure of resistance to oxidation, oxidation rate and extent of oxidation, a measure of diene production in both groups, was studied. RESULTS It was observed that lipid hydroperoxide and AuAb-oxLDL levels in patients with Behçets disease were significantly higher, but erythrocyte SOD, CAT, plasma GSH-Px activities, and TAS were significantly lower than those in healthy subjects. Susceptibility of LDL to oxidation in the patients was found to be increased. Total cholesterol, LDL-C and apo B levels and acute phase reactants were significantly higher, but HDL-C and apo AI levels were significantly lower, in patients when compared to healthy subjects. The levels of AuAb-oxLDL in patients were found to correlate with TAS, total cholesterol, LDL-C, lipid hydroperoxide and erythrocyte SOD activities (r = -0.62, p < 0.01; r = 0.64, p < 0.01; r = 0.55, p < 0.01; r = 0.81, p < 0.01; r = -0.63, p < 0.01, respectively). In addition, lipid hydroperoxide levels were found to correlate with total cholesterol, LDL-C and erythrocyte SOD activities (r = 0.45, p < 0.05; r = 0.45, p < 0.05; r = -0.46, p < 0.05, respectively). PAI-1 and sICAM-1 were found to be increased in the patients and correlated with AuAb-oxLDL and lipid hydroperoxide levels (r = 0.56, p < 0.01; r = 0.67, p < 0.01 and r = 0.59, p < 0.01; r = 0.61, p < 0.01, respectively). CONCLUSIONS It was concluded that the observed increase of lipid, lipoproteins, lipid hydroperoxide, susceptibility of LDL to oxidation, autoantibodies against ox-LDL levels and decrease of antioxidant enzyme activities and total antioxidant status and increased secretion of endothelial derivated peptides including sICAM and PAI-1, and their interactions may indicate that there is a tendency to atherothrombotic events in patients with Behçets disease.

Decreased nitric oxide end-products and its relationship with high density lipoprotein and oxidative stress in people with type 2 diabetes without complications

Diabetes mellitus is associated with hyperglycaemia, hyperlipoproteinaemia, increased oxidative stress and decreased nitric oxide production from endothelial cells. In the present study the aim was to determine the relationships between serum lipids, lipoproteins, erythrocyte malondialdehyde (eMDA), as a marker for oxidative stress, and serum nitrite and nitrate levels, as degradation products of nitric oxide in type 2 diabetic patients without complications. The study group included 30 patients and 30 sex- and age-matched healthy volunteers. Total cholesterol, triacylglycerol, LDL cholesterol, apo B, HbA(1c) and glucose levels in patients were significantly higher than in controls, and HDL cholesterol levels lower. Increased eMDA levels and decreased nitrate and nitrite+nitrate levels (+/-SD) were observed in patients compared to controls (87+/-22 vs 59+/-17 nmol/g-Hb (P<0.01); 11.8+/-8.6 vs 22.8+/-10.8 micromol/l (P<0.01); and 16.8+/-11.0 vs 28.8+/-11.3 micromol/l (P<0.01), respectively). When the patients were divided into two groups according to HDL cholesterol levels (< or =0.91 and >0.91 mmol/l), total plasma nitric oxide end-products were found to be decreased in patients with low HDL levels compared to those patients with high HDL levels [men, 11.7+/-6.4 vs 24.6+/-14.9 micromol/l (P<0.01); women, 12.5+/-6.6 vs 21.4+/-6.6 micromol/l (P<0.01]. Nitrite and nitrate levels were correlated with HDL cholesterol (r=0.50, P<0.05) and eMDA (r=-0.52, P<0.05). It was concluded that the patients with unregulated blood glucose levels have abnormal lipid and lipoprotein metabolism and decreased nitric oxide end-products, with relationships between nitric oxide products and dyslipidaemia, especially between low HDL cholesterol levels and increased oxidative stress.

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.

The significance of autoantibodies against oxidatively modified low-density lipoprotein (LDL) in patients with psoriasis.

Psoriasis is associated with changes in plasma lipid and lipoproteins, which may play a role in the development of occlusive vascular disease. The oxidation of low-density lipoprotein (LDL) is considered a key event in the development and progression of atherosclerosis. Autoantibodies against oxidized LDL (auAb-oxLDL) may contribute to understanding the relationship between oxidative processes and development of atherosclerosis. Thirty-three patients with psoriasis and 30 matched control subjects were investigated. LDL oxidation was evaluated as the presence of autoantibodies against LDL oxidatively modified with Cu++, by an ELISA system in the patients and control sera. AuAb-ox LDL levels of the patients were found to be significantly increased compared with a control group. 42% of the patients and 3.3% of the control subjects had higher auAb-ox LDL levels than the cut-off point (352 mU/ml). The levels of auAb-ox LDL were found to be correlated with PASI score (r = 0.67, p < 0.01). Also, The antibody level was found to be correlated with polymorphonuclear elastase and alpha-1 antitrypsin levels (r = 0.58, p < 0.05; r = 0.51, p < 0.05, respectively). It was concluded that increased levels of auAb-oxLDL in the psoriatic patients may be a consequence of the interaction between imbalance of oxidant-antioxidant system and lipoproteins, and the measurement of auAb-oxLDL in the patients may mirror in vivo occurrence of oxidative processes.

Evaluation of Plasma Endothelin-1 Levels in Patients with Cerebral Infarction

Endothelin-1 (ET-1) is a vasoconstrictor peptide derived from endothelium. Many authors have shown that ischemic stroke is associated with elevated plasma ET-1 levels. Also, the present findings related to plasma ET-1 levels with clinical status, size of the infarction, location of the infarction, and prognosis of the cerebral infarction were contradictory. In this study, plasma ET-1 levels in 30 patients with cerebral infarction within 72 hours after the onset of focal neurologic deficit and at their seventh day postinfarction were measured by a microplate enzyme immunoassay. Thirty sex- and age-matched healthy subjects were accepted as a control group. The mean plasma ET-1 concentrations in patients on admission, in patients at day 7, and in control subjects were 1.93 ± 1.79, 1.03 ± 1.02, and 0.65 ±0.32 fmol/mL, respec tively. The mean plasma ET-1 level of patients on admission was found to be significantly higher than in patients at day 7 and in control subjects (p < 0.05). No significant difference in ET-1 levels was observed between the patients at day 7 and control subjects. Furthermore, there was no correlation between plasma ET-1 concentration and size of infarction, location of infarction, degree of clinical neurologic deficit, or prognosis of cerebral infarction. It was concluded that plasma ET-1 levels shortly after ischemic stroke were increased, which may be associated with the acute-phase reaction of cerebral infarction and may have deleterious effects on development of neuronal injury.

TGF-beta and TNF-alpha producing effects of losartan and amlodipine on human mononuclear cell culture.

Aim:  The modulation of cytokine release, which affects adhesion of leucocytes to endothelial cells, and proliferation of peripheral blood mononuclear cells with antihypertensive drugs was explored.

Effect of coronary angiography on plasma endothelin-1 and nitric oxide concentrations.

Endothelium takes part in the regulation of vascular tone through the production of endothe lium-derived relaxing factor, nitric oxide (NO), and the contracting factor endothelin-1 (ET-1). Induction of ET-1 and NO is influenced by many stimuli including hypoxia and shear stress. Some of these stimuli may arise during coronary angiography (CAG). In this study, the authors aimed to show endothelial response in patients undergoing CAG by evaluating plasma ET-1 and NO end-products including nitrite and nitrate concentrations. Twenty-four male patients with a mean age of 54.3 years (age range: 37-70) were included in the study. The patients had no coronary atherosclerotic lesions established by CAG. The mean time of the CAG procedures was 24.8 minutes, with a range of 19-33 minutes. Immediately before blood sampling, systolic and diastolic blood pressures were recorded. The mean blood pressures before and after CAG were 140/90 and 150/95, respectively. End products of NO radical, nitrite and nitrate (NOx), in plasma were used as a marker for the production of NO radical. ET-1 concentrations were measured by ELISA method. Significant increases in ET-1 concentrations were observed during CAG while no change observed in NOx concentrations. Duration of the CAG procedure was found to be correlated with the percent increase of the plasma ET-1 concentrations during CAG (r = 0.45, p<0.05, Figure 1), but not with NOx concentrations. Plasma ET-1 concentrations in patients who were cigarette smoking were found higher than those of patients who were nonsmokers (1.26 ±0.38 and 2.97 ±0.87 fmol/L, respectively). It was concluded that endothe lial cells show increased ET-1 production as a response of some mechanical or emotional stimuli during CAG procedure that may play an important role in the regulation of vascular tonicity and some pathological processes. The authors suggest that duration and manipulation of CAG may be an important factor in plasma ET-1 concentrations.

Effects of Enalaprilat on Acute Necrotizing Pancreatitis in Rats

The aim of this study was to investigate the influence of enalaprilat on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in a significant increase in the mortality rate, pancreatic necrosis, serum activity of amylase, alanine aminotransferase (ALT), and interleukin-6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, and tissue activity of myeloperoxidase (MPO) and maondialdehyde (MDA) in the pancreas and lung, and a significant decrease in concentrations of calcium, blood pressure, urine output and p02. The use of enalaprilat inhibited the changes in urine output, blood pressure, serum concentration of urea, p02, and tissue activity of MPO and MDA in the pancreas and lungs. It reduced the mortality and pancreatic damage. Enalaprilat demonstrated a beneficial effect on the course of ANP in rats; therefore, it may be used in the treatment of acute pancreatitis.

Increased Plasma Endothelin-1 Levels in Patients With Intracerebral Hemorrhage

Endothelins (ETs) are discovered peptides that are widely distributed in neurons and nonneuronal cells of the human nervous system. Previous studies showed that ischemic stroke may be associated with increased plasma ET-1 levels. There are no studies to show plasma ET-1 levels in intracerebral hemorrhage. Plasma ET-1 levels in 30 patients with cerebral hemorrhage within 72 hours after the onset of focal neurological deficit were measured by a microplate enzyme immunoassay. Thirty sex- and age-matched healthy subjects were accepted as a control group. The clinical neurological status in the patients was evaluated according to the modified Matthew Scale. The mean plasma ET-1 level in hemorrhagic stroke patients was significantly higher than in control subjects (2.39±2.08 v 0.65±0.32 fmol/mL, (P < .05). There was a significant difference in ET levels between patients who died in the hospital and patients who survived (P < .05). The mean ET-1 concentration in patients with severe neurologic deficit was significantly higher than in patients with mild neurologic deficit (P < .05). There was a correlation between hematoma volumes and plasma ET-1 levels in the patients (r = 0.66, Pt < .001). The mean plasma ET-1 concentration was found to be significantly higher in patients with intraventricular hemorrhage than in patients without intraventricular hemorrhage (P < 0.05). There were no significant differences in ET-1 levels between supratentorial and infratentorial subgroups or among supratentorial subgroups (P > .05). It was concluded that plasma ET-1 levels were increased in the acute period of hemorrhagic stroke. Plasma ET-1 levels may be associated with hematoma volume, which is related to a poor prognosis of the cerebral hematoma. We suggest that increased plasma ET-1 levels may be a consequence of local cerebral hemorrhage or the acute stress condition of the disease.

The anti-inflammatory effect of hydrogen sulphide on acute necrotizing pancreatitis in rats

OBJECTIVE The aim of this study was to investigate the dose-dependent anti-inflammatory effect of the Hydrogen sulfidedonor sodiumhydrosulphide on acute necrotizing pancreatitis in rats. MATERIAL AND METHODS A total of 42 male Sprague-Dawley rats were divided into 4 groups: sham+saline (group 1), sham+NaHS (group 2), acute necrotizing pancreatitis+saline (group 3), and acute necrotizing pancreatitis+NaHS (group 4). Acute pancreatitis was induced in rats in groups 3 and 4 with the infusion of glycodeoxycholic acidinto the biliopancreatic canal and infusion of cerulein parenterally. In group 4, 10 mg/kg NaHS was administered intraperitoneally after cerulein infusion. Tests for liver and kidney function, interleukin-6, lactate dehydrogenase in bronchoalveolar lavage, and malonyaldehyde and myeloperoxidase activities in pancreas and lung tissue were performed, and histopathologic examination of pancreas was conducted. RESULTS In groups 3, a significant increase in amylase, alanine aminotransferase, urea, interleukine-6, lungmalondialdehyde and myeloperoxidase activities, pancreas myeloperoxidase activity, edema, and necrosis in pancreas tissue and a significant decrease in serum calcium levels were detected (p<0.05). In group 4, addition of NaHS resulted in a significant decrease in lactate dehydrogenase level in bronchoalveolar lavage, amount of urea, lung myeloperoxidase activity, and pancreatic edema (p<0.05). CONCLUSION Although not in pancreatic necrosis, hydrogen sulphide has an anti-inflammatory effect especially in the inflammatory process in lung and edema in pancreasin acute necrotizing pancreatitis at particular doses. With further studies evaluating the anti-inflammatory effects of hydrogen sulphide, we believe it can be used in the treatment of edematous acute pancreatitis and the related complications in lungs.