Asım Örem

Evaluation of the atherogenic tendency of lipids and lipoprotein content and their relationships with oxidant-antioxidant system in patients with psoriasis.

BACKGROUND Psoriasis is a common chronic and recurrent inflammatory skin disease that can occur due to abnormalities in essential fatty acid metabolism, lymphokine secretion, free radical generation, lipid peroxidation and eicosanoid metabolism, and has been associated with increased frequency of cardiovascular events. The current study was designed to evaluate plasma lipids, susceptibility of LDL to oxidation and oxidant-antioxidant status and their relationships in patients with psoriasis. METHODS The study group included 35 patients with psoriasis (18 females and 17 males), and 35 sex- and age-matched healthy volunteers (16 females and 19 males). From blood samples, their lipids, lipoproteins, acute phase reactants, lipid peroxidation products [lipid hydroperoxide (LHP) and malondialdehyde (MDA)], antioxidant enzymes [glutathione peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT)], total antioxidant status (TAS) and autoantibodies against oxidized low-density lipoprotein (AuAb-oxLDL) levels were determined. Moreover, the susceptibility of copper-induced in vitro oxidation of LDL was examined. RESULTS The mean levels of atherogenic lipids (total cholesterol [TC], triacylglycerol [TG] and LDL cholesterol [LDL-C]), acute-phase reactants (CRP, ESR, PMNLs, ceruloplasmin and fibrinogen) and lipid peroxidation products, AuAb-oxLDL levels in patients with psoriasis were found to be significantly higher than those of healthy subjects. On the other hand, TAS and antioxidant enzyme activities (CAT, SOD and GSH-Px in erythrocyte and SOD in plasma) were significantly lower when compared to healthy subjects. The lag times [t(lag)], a measure of resistance to oxidation of LDL, were also lower. The levels of AuAb-oxLDL in patients were correlated with TC, LDL-C, plasma LHP, erythrocyte MDA, oxidized LDL-MDA (oxLDL-MDA), fibrinogen, CRP, PMNL levels and plasma SOD activities (r = 0.69, P < 0.01; r = 0.64, P < 0.01; r = 0.38, P < 0.05; r = 0.65, P < 0.01; r = 0.34, P < 0.05; r = 0.34, P < 0.05; r = 0.53, P < 0.01, r = 0.34, P < 0.05; r = -0.67, P < 0.01, respectively). On the other hand, t(lag) was correlated negatively with the levels of VLDL-TG, VLDL-TC and LDL-TG but positively correlated with the levels of TAS in psoriatics (r = -0.49, P < 0.01; r = -0.49, P < 0.01, r = -0.65, P < 0.05; r = 0.37, P < 0.05). CONCLUSIONS It was concluded that the psoriatic patients could be considered as a group with an increased atherosclerotic risk because of increased oxidant stress, decreased antioxidant capacity and susceptibility in lipid profile and lipoprotein content to atherogenicity.

Plasma homocysteine and its relationships with atherothrombotic markers in psoriatic patients

BACKGROUND Hyperhomocysteinemia may constitute an independent risk factor for cardiovascular disease and may promote atherothrombosis. Psoriasis is one of the diseases associated with increased atherothrombosis. The aim of the present study was to examine serum total homocysteine (tHcy) level and its relationships with atherothrombotic markers. METHODS The study group included 30 patients with psoriasis (17 females and 13 males) with a mean age of 34.2 (age range: 27-40) and 30 sex and age matched healthy volunteers (15 females and 15 males) with a mean age of 36.7 (age range: 26-48). The concentrations of lipids, lipoproteins, acute phase reactants, tHcy and atherothrombotic markers [fibronectin, soluble vascular adhesion molecules-1 (sVCAM-1), soluble intercellular adhesion molecules-1 (sICAM-1), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), autoantibodies against oxidized LDL (AuAb-oxLDL)] were determined. RESULTS The mean levels of serum tHcy, fibrinogen, fibronectin, sICAM, PAI-1 and AuAb-oxLDL were increased in patients whereas tPA, vitamin B(12) and folate levels were decreased significantly. Increased levels of sVCAM were not statistically significant. tHcy levels were negatively correlated with vitamin B(12) (r=-0.40, P=0.027) and positively correlated with PAI-1 and AuAb-oxLDL levels (r=0.46, P=0.011; r=0.39, P=0.035, respectively). CONCLUSIONS It was concluded that the increased homocysteine concentration and altered endothelial cell-mediated proteins associated with increased lipids and LDL oxidation may play an important role for the development of atherothrombotic complications with psoriasis.

Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in patients with relapsing-remitting multiple sclerosis treated with interferon beta

OBJECTIVES Matrix metalloproteinases (MMPs), particularly MMP-9, facilitate T-cell migration into the central nervous system. They play a key role in the disruption of the blood-brain barrier (BBB) and thus in the pathogenesis of multiple sclerosis. Interferon betas (IFNbeta) ability to alter the balance between MMP-9 and MMP-9s natural inhibitor, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), may play a role in stabilizing the BBB. The aim of this study, was to evaluate serum MMP-9 and TIMP-1 and cerebrospinal fluid (CSF) TIMP-1 levels in patients with relapsing-remitting multiple sclerosis (RRMS) treated with IFNbeta-1a. PATIENTS AND METHODS Blood and CSF samples from 14 patients with RRMS before and 6 months after IFNbeta therapy and 14 age and sex-matched controls were obtained. Levels of MMP-9 and TIMP-1 were measured using ELISA. RESULTS Before treatment, patients with MS had higher levels of serum MMP-9 and a higher MMP-9/TIMP-1 ratio than the controls. Although serum levels of TIMP-1 were lower in RRMS patients than in the controls, the differences did not reach statistical significance. CSF levels of TIMP-1 were significantly lower in RRMS patients. In the sixth month of IFNbeta therapy serum MMP-9 and the MMP-9/TIMP-1 ratio were significantly decreased, whereas the changes in serum TIMP-1 were not statistically significant. There was a significant increase in CSF TIMP-1 levels in the sixth month of IFNbeta therapy. CONCLUSIONS Our result shows that RRMS patients have an impaired MMP-9 and TIMP-1 balance, and that 6 months of IFNbeta therapy is beneficial in restoring this balance.

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.

Effect of Antiepileptic Drugs on Plasma Lipids, Lipoprotein (a), and Liver Enzymes

We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P < .05). The mean pretreatment lipid levels among the groups were not significantly increased. The mean lipoprotein (a) levels were significantly increased in all groups at 3, 6, and 12 months of the treatment period (P < .05). The increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol at 3, 6, and 12 months was statistically significant in group 1 (P < .05). The higher levels in lipoprotein (a) (mean > 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70—74).

Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects

BACKGROUND Tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. However, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. METHODS The antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. Twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. These were control diet I (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18%-20% of the total daily energy intake), and control diet period II (4 weeks). The cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (FMD) technique, low-density lipoprotein (LDL) oxidation products and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as lipids and lipoprotein levels were monitored. RESULTS Consumption of a hazelnut-enriched diet significantly improved FMD (56.6%), total cholesterol (-7.8%), triacylglycerol (-7.3%), LDL-cholesterol (-6.17%), and high-density lipoprotein cholesterol (6.07%) compared with the control diet I. Oxidized-LDL, hs-CRP, and sVCAM-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets I and II. Modest correlations between sVCAM-1 and FMD and between sVCAM-1 and hs-CRP were observed (r = -0.49, P < .025; r = 0.66, P < .001, respectively). CONCLUSION Hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing LDL oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. These beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. Therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit.

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.

The effects of lipid-lowering therapy on low-density lipoprotein auto-antibodies: relationship with low-density lipoprotein oxidation and plasma total antioxidant status

BackgroundOxidized low-density lipoprotein (Ox-LDL) is believed to play an important role in the progression of atherosclerosis. Oxidative modification of low-density lipoprotein (LDL) is a prerequisite for rapid accumulation of LDL in macrophages and for the formation of foam cells. Because of high antioxidant levels in plasma, LDL oxidation is suggested to occur mainly in the subendothelial space of the arterial wall, where there is the concomitant presence of large amounts of reactive oxygen species generated by endothelial cells and activated leukocytes. After Ox-LDL formation, antibodies against this form of LDL may occur. Auto-antibodies against Ox-LDL (AuAb-Ox-LDL) show directly in in-vivo LDL oxidation. Many studies have indicated that the amount of antibodies in serum is positively correlated to the rate of progression of atherosclerotic plaques. Design and methodsIn this study the effect of lipid-lowering therapy on the levels of AuAb-Ox-LDL in patients with dyslipidemia was determined using atorvastatin (10 mg/day), and the relationship between the antibodies and plasma total antioxidant status (TAS) and LDL oxidation capacity was also investigated. Serum levels of AuAb-Ox-LDL, lipids, lipoproteins, TAS and susceptibility of LDL to oxidation were determined using lag time in 44 patients with dyslipidemia (29 with hypercholesterolemia and 15 with mixed-type hyperlipidemia). ResultsAfter lipid-lowering therapy, serum levels of AuAb-Ox-LDL were found to be significantly decreased, by 18.7%, while lag time and plasma TAS were increased (31.3% and 7.6% respectively) in patients with dyslipidemia. The percentage change in lag time was found to be negatively correlated to the percentage change in AuAb-Ox-LDL (r  = −0.31, P  < 0.05). The percentage change in lag time also showed a positive correlation with the percentage change in TAS (r  = 0.58, P  < 0.01). AuAb-Ox-LDL levels decreased by 21.7% in patients with hypercholesterolemia and by 12.6% in patients with mixed-type hyperlipidemia. Also AuAb-Ox-LDL levels in patients with hypercholesterolemia were higher than in those with mixed-type hyperlipidemia (367 ± 294 compared with 300 ± 176 mU/l). ConclusionIt was concluded that lipid-lowering therapy may contribute to the reduction in levels of AuAb-Ox-LDL and the increase in the antioxidant capacity of plasma LDL and TAS. It was also suggested that the measurement of antibodies against Ox-LDL during lipid-lowering therapy may be used as an important marker for representing in-vivo LDL oxidation and atherosclerotic processes.

Prognostic Value of Red Cell Distribution Width in Patients With Pulmonary Embolism

Elevated red blood cell distribution width (RDW) has been associated with adverse outcomes of heart failure and pulmonary hypertension. A total of 702 consecutive patients with acute pulmonary embolism (PE) were evaluated. There was a graded increase in mortality rate with RDW quartiles of 5.8% in quartile I (≤13.6), 9.7% in quartile II (13.7%-14.5%), 13.1% in quartile III (14.6%-16.3%), and 20% in quartile IV (>16.3%; P < .001). Patients who died had higher baseline RDW values (16.1% [11.7-28.3] vs 14.5% [10.7-32.5]; P < .001). The optimal cutoff value of RDW for predicting in-hospital mortality was ≥15%. The area under the curve of mortality for RDW was 0.649 (confidence interval [CI]: 0.584-0.715); the negative predictive value was 93%. In multivariable regression analysis, RDW remained associated with an increased odds of death (odds ratio: 1.2, 95% CI: 1.1-1.4). High RDW level was an independent predictor of short-term mortality in PE. The RDW levels may provide a potential marker to predict outcome in patients with PE.

Effect of Antiepileptic drugs on plasma lipoprotein (a) and other lipid levels in childhood.

Antiepileptic drugs may alter plasma lipid status in epileptic patients. We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on plasma levels of lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A, and apolipoprotein B in 22 epileptic children. The children were separated as group 1, seven children, mean age 1.6 ± 0.2 years, treated with phenobarbital, 5 mg/kg/day, twice daily; group 2, seven children, mean age 9.8 ± 1.2 years, treated with carbamazepine, 20 mg/kg/day, twice daily; and group 3, eight children, mean age 6.8 ± 0.6 years, treated with valproate, 20 mg/kg/day, twice daily. Plasma lipoprotein (a) and other lipid levels were studied before (pretreatment) and at 3 and 6 months of treatment. Friedman two-way analysis of variance and Wilcoxons signed-rank test were used for statistical analysis, and the results were expressed as the mean and standard error of the mean. The mean age of children in group 1 was significantly low, compared with groups 2 and, 3 (P < .001). The mean pretreatment lipid levels between the groups were not significant. The increase in lipoprotein (a) at 3 and 6 months and high-density lipoprotein cholesterol at 6 months was statistically significant in group 1 (P <.025). We suggest a careful monitoring of plasma levels of lipoprotein (a) and other lipids in epileptic children treated with antiepileptic drugs. (J Child Neurol 2001;16:367-369).