Oxidative stress and erythrocyte integrity in end-stage renal failure patients hemodialysed using a vitamin E-modified membrane. Evaluation of a Novel Vitamin E Coated Cellulosic Membrane Hollow Fiber Dialyzer Vitamin E‐‐Bonded Cellulose Membrane, Lipoperoxidation, and Anemia in Hemodialysis Patients Effects of a vitamin E-modified dialysis membrane and vitamin C infusion on oxidative stress in hemodialysis patients. Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients. Simvastatin and oxidative stress in humans: A randomized, double-blinded, placebo-controlled clinical trial Effects of vitamin C infusion and vitamin E-coated membrane on hemodialysis-induced oxidative stress. The vitamin E debate: implications for ongoing trials of pre‐eclampsia prevention A Vitamin E-Coated Polysulfone Membrane Reduces Serum Levels of Inflammatory Markers and Resistance to Erythropoietin-Stimulating Agents in Hemodialysis Patients: Results of a Randomized Cross-Over Multicenter Trial Effects of erythropoietin and vitamin E-modified membrane on plasma oxidative stress markers and anemia of hemodialyzed patients. Vitamin C Supplementation Decreases Oxidative Stress Biomarker F2-Isoprostanes in Plasma of Nonsmokers Exposed to Environmental Tobacco Smoke Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients. Supplementation With Conjugated Linoleic Acid Causes Isomer-Dependent Oxidative Stress and Elevated C-Reactive Protein: A Potential Link to Fatty Acid-Induced Insulin Resistance Molecular biology-based assessment of vitamin E-coated dialyzer effects on oxidative stress, inflammation, and vascular remodeling. Effects of vitamin E-coated membrane dialyser on markers of oxidative stress and inflammation in patients on chronic haemodialysis. Antioxidants as a Preventive Treatment for Epileptic Process: A Review of the Current Status Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers. Does short-term vitamin C reduce cardiovascular risk in type 2 diabetes? The effects of 1-year treatment with a haemodiafiltration with on-line regeneration of ultrafiltrate (HFR) dialysis on biomarkers of oxidative stress in patients with chronic renal failure Sesame supplementation does not improve cardiovascular disease risk markers in overweight men and women. Comparative evaluation of oxidative and antioxidative capacity during high-flux hemodialysis using two different membranes. The clinical epidemiology of cardiovascular disease in chronic kidney disease The relationship between dose of vitamin E and suppression of oxidative stress in humans.
Oxidative stress has been implicated in a range of disease states , including end-stage renal failure treated with hemodialysis . Hemodialysis with vitamin E-modified membranes reduces lipid peroxidation , but the effect on erythrocyte integrity has not been determined . This study compared antioxidant defense parameters and the resistance of erythrocytes to free radical-mediated hemolysis in patients dialysed with cellulose acetate membranes at baseline and with a vitamin E-modified membrane ( Excebrane Clirans ; Terumo Corporation ) for 13 wk .  Resistance of erythrocytes to free radical attack was assessed in vitro using the peroxyl hemolysis test . The time to 50 % hemolysis ( T50 % ) increased significantly during the first 6 wk of Excebrane use ( p < 0.05 ) , but this parameter returned to baseline by 13 wk . Glutathione concentration and erythrocyte superoxide dismutase activity were unchanged during the study , but glutathione peroxidase activity increased from low levels at baseline and became significantly higher at 6 and 13 wk ( p < 0.001 ) . Total erythrocyte polyunsaturated fatty acid content and C18:2 level increased ( p < 0.001 ) and saturated fatty acids ( total , C16:0 , C18:0 , C22:0 and C24:0 ) decreased ( p < 0.03 ) . Total monounsaturated fatty acid content was unchanged . The increased resistance of erythrocytes to hemolysis , the increased glutathione peroxidase activity , and the increased degree of unsaturation of fatty acids in the erythrocyte membrane are compatible with a reduction of oxidative stress during hemodialysis with vitamin E-modified membranes Adverse physiologic effects accompany hemodialysis . Biocompatible dialyzer membranes may both limit oxidative stress and decrease & bgr;2-microglobulin production , thereby reducing patient morbidity . We compared st and ard solute clearance , lipid , and antioxidant effects of a novel cellulosic membrane dialyzer modified with covalently bonded vitamin E ( Excebrane Clirans E15 , Terumo Australia ) with st and ard cellulosic and polysulphone membrane dialyzers .  Stable adult hemodialysis patients taking no lipid lowering or antioxidant therapy ( n = 17 ; 9 male , 8 female ) were recruited into a 10 week , prospect i ve , unblinded study . Measurements were made at baseline on their usual dialyzer and after 2 , 4 , and 10 weeks of Excebrane use . Excebrane demonstrated good in vivo clearance of st and ard solutes relative to surface area . Predialysis & bgr;2-microglobulin levels were unchanged with time and were significantly lower postdialysis than with cellulose acetate ( p < 0.05 ) . Oxidized low density lipoprotein levels as measured by nitrotyrosine residues were high predialysis , but tended to decrease with both membranes ( p > 0.05 ) . Total antioxidant status fell during dialysis ( p < 0.0005 ) , but plasma vitamin A and E concentrations increased ( p = 0.007 and p = 0.02 , respectively ) . Baseline vitamin A levels were high in all patients and , along with vitamin E , total antioxidant status and lipid profiles did not change over time with Excebrane use . Excebrane is an efficient , biocompatible membrane with no deleterious effects on & bgr;2-microglobulin or lipids . More long-term study is merited In hemodialysis patients , oxidative stress results from an imbalance between the production of reactive oxygen species and antioxidant defense mechanisms . Recently , a new dialysis multi‐‐layer membrane has been developed , by modifying the inner surface of regenerated cellulose to support a vitamin E coating . The aim of our study was to investigate the effects of hemodialysis treatment with vitamin E‐‐modified membrane on anemia and erythropoietin requirement in a group of chronic uremic patients . Ten uremic , non diabetic , patients on st and ard bicarbonate dialysis were treated with vitamin E‐‐bonded dialysis membrane for 12 months . Hematological parameters , erythropoietin requirement , serum vitamin E and serum malonyldialdehyde ( ( MDA ) ) were evaluated before starting the study and monthly . No significant changes in hemoglobin level , RBC count , hematocrit and EPO requirement were observed . Basal vitamin E levels were in the normal range ( ( 13.0±2.88 mg//L vs. 14.79±3.12 mg//L ; NS ) ) . On the contrary , basal MDA levels were higher than those observed in the control group ( ( 1.87±0.36 vs. 1.13±0.18 mmol//mL ; p < 0.01 ) ) and a significant decrease of MDA levels was found after 1 month of Excebrane ® treatment ( ( 1.39±0.25 nmol//mL ; p < 0.02 ) ) . In conclusion , the role of the “ oxidative hemolysis ” in the pathogenesis of anemia in CHD patients is still not clearly defined , but it could be of minor clinical relevance . Although the effectiveness of vitamin E‐‐coated membranes as a scavenger of ROS allows a better control of intradialytic oxidative stress , it does n't seem to contribute to clinical management of anemia in these patients Hemodialysis deteriorates oxidative stress . Vitamin E is an antioxidant whose regeneration is provided for by vitamin C. The authors tested the effects of a vitamin E-modified membrane ( E ) , nonmodified cellulose membrane ( O ) , and vitamin C infusion ( 500 mg , C ) into the arterial blood line during dialysis on parameters of oxidative stress . In a short-term study , 24 patients were subjected to a single dialysis session  with E , O , E with C , and O with C protocol s. In a long-term study ( 12 weeks ) , 20 patients were r and omized into groups with C and without C on each dialysis , and both groups had dialysis using O , E , and again O membrane for 4 weeks each . In the short-term study , thiobarbituric acid reacting substances ( TBARS ) in plasma rose after dialysis ( p < 0.02 ) with O , and no changes were observed in the other 3 protocol s. In the long-term study , predialysis TBARS declined when using E both in the groups with C ( p < 0.02 ) and without C ( p < 0.05 ) . A switch over to O result ed in TBARS returning to baseline levels . The E membrane prevented an increase in lipid peroxidation during single dialysis , and long-term use of the E membrane also result ed in a decrease in the predialysis lipid peroxidation level . The antioxidant capacity of the E membrane was not enhanced by vitamin C infusion . High doses of vitamin C administered during dialysis using a nonmodified cellulose membrane prevented an increase in lipid peroxidation , most probably due to the enhanced rate of endogenous vitamin E regeneration BACKGROUND Dyslipidaemia , inflammation and oxidative stress are prominent risk factors that potentially cause vascular disease in haemodialysis patients .  Dialysis modalities affect uraemic dyslipidaemia , possibly by modifying oxidative stress , but the effects of dialyser flux and membrane material on atherogenic remnant particles and oxidized low-density lipoproteins ( LDL ) are unknown . METHODS We performed a r and omized crossover study in 36 patients on haemodialysis  to analyse the effect of dialyser flux and membrane material on plasma lipids , apolipoproteins and markers of inflammation and oxidative stress . Stable patients on low-flux dialysis with polysulphone for > /=6 weeks were assigned to high-flux polysulphone or high-flux modified cellulose with similar dialyser surface area and permeability characteristics and crossed over twice every 6 weeks . RESULTS Thirty patients completed the study per protocol . Treatments with high-flux polysulphone and modified cellulose lowered serum triglyceride ( by 20 % and 10 % , respectively ; P<0.05 ) and remnant-like particle cholesterol by 32 % ( P<0.001 ) and 11 % ( NS ) after the first 6 weeks of treatment . Oxidized LDL decreased significantly with high-flux polysulphone , but not with modified cellulose . Apolipoproteins CII and CIII were reduced , whereas the ratio CII/CIII was increased ( all P<0.05 ) . Acute-phase proteins and LDL and high-density lipoprotein cholesterol remained unaffected . CONCLUSIONS This r and omized crossover study demonstrates a potent effect of high-flux haemodialysis on uraemic dyslipidaemia .  Polysulphone membrane material showed superiority on oxidatively modified LDL , an indicator of oxidative stress in haemodialysis patients Simvastatin reduces the blood concentration of cholesterol by inhibiting hydroxymethylglutaryl-coenzyme A reductase , the rate-limiting enzyme in cholesterol synthesis , and thereby reduces the risk of cardiovascular disease . In addition , simvastatin treatment leads to a reduction in fluxes in mitochondrial respiratory complexes I and II and might thereby reduce the formation of reactive oxygen species , which have been implicated in the pathogenesis of arteriosclerosis . Therefore , we hypothesized that simvastatin may reduce oxidative stress in humans in vivo . We conducted a r and omized , double-blinded , placebo-controlled study in which subjects were treated with either 40 mg of simvastatin or placebo for 14 days . The endpoints were six biomarkers for oxidative stress , which represent intracellular oxidative stress to nucleic acids , lipid peroxidation and plasma antioxidants , that were measured in urine and plasma sample s. A total of 40 participants were included , of which 39 completed the trial . The observed differences between simvastatin and placebo groups in the primary outcomes , DNA and RNA oxidation , were small and nonsignificant ( p=0.68 ) , specifically , 3 % in the simvastatin group compared to 7.1 % in the placebo group for DNA oxidation and 7.3 % in the simvastatin group compared to 3.4 % in the placebo group . The differences in biomarkers related to plasma were not statistically significant between the treatments groups , with the exception of total vitamin E levels , which , as expected , were reduced in parallel with the reduction in plasma cholesterol . In healthy young male volunteers , short-term simvastatin treatment , which considerably reduces cholesterol , does not lead to a clinical ly relevant reduction in a panel of measures of oxidative stress . Whether simvastatin has effects on oxidative stress in diseased population s , such as diabetes or hemochromatosis , where oxidative stress is prominent , is unknown but seems unlikely Chronic hemodialysis ( HD ) patients manifest anemia and atherosclerosis with associated oxidative stress . We explored whether intravenous infusion of vitamin C ( VC ) and /or use of vitamin E (VE)-coated dialysis membrane could palliate HD-evoked oxidative stress . Eighty patients undergoing chronic HD were enrolled and r and omly assigned into four groups : HD with intravenous VC ( n=20 ) , HD with VE-coated dialyzer ( n=20 ) , HD with both ( n=20 ) , and HD with neither ( n=20 ) . We evaluated oxidative stress in blood and plasma , erythrocyte methemoglobin/ferricyanide reductase ( red blood cells (RBC)-MFR ) activity , plasma methemoglobin , and pro-inflammatory cytokines in these patients . All patients showed marked increases ( 14-fold ) in blood reactive oxygen species ( ROS ) after HD . The types of ROS were mostly hydrogen peroxide , and in lesser amounts , O2 * - and HOCl . HD result ed in decreased plasma VC , total antioxidant status , and RBC-MFR activity and increased plasma and erythrocyte levels of phosphatidylcholine hydroperoxide ( PCOOH ) and methemoglobin . Intravenous VC significantly palliated HD-induced oxidative stress , plasma and RBC levels of PCOOH , and plasma methemoglobin levels and preserved RBC-MFR activity . The VE-coated dialyzer effectively prevented RBCs from oxidative stress , although it showed a partial effect on the reduction of total ROS activity in whole blood . In conclusion , intravenous VC plus a VE-coated dialyzer is effective in palliating HD-evoked oxidative stress , as indicated by hemolysis and lipid peroxidation , and by overexpression of proinflammation cytokines in HD patients . Using VE-coated dialyzer per se is , however , effective in reducing lipid peroxidation and oxidative damage to RBCs A potential role for oxidative stress in the pathophysiology of pre-eclampsia was first proposed by Stark in 1993 . Synthesis of free radicals by a dysfunctional placenta , and possibly by maternal leucocytes and endothelium , seems to play a central role in this association . Free radicals , through oxidative damage of biomolecules and lipid peroxidation , can initiate maternal vascular endothelial dysfunction and leucocyte activation . A comprehensive review of the role of oxidative stress in pre-eclampsia has been recently published . Antioxidants such as vitamin C and vitamin E have been proposed as potential therapeutic or prophylactic treatment for pre-eclampsia .  This suggestion was supported by the observation that women with pre-eclampsia have lower plasma vitamin C concentrations . Both in vitro and in vivo studies suggest that there is an interaction between vitamin C and vitamin E , with vitamin C possibly exerting a ‘ redox ’ recycling effect on oxidised vitamin E within lipoproteins and membranes . The vitamin C to E ratio may be of central importance in protecting against the damaging effects of reactive oxygen species . To date , three placebo-controlled trials have assessed the effect of vitamins C and E on  pre-eclampsia .  Although no benefits were found when supplementation was given to women with diagnosed pre-eclampsia , a combination of 1 g/day of vitamin C and 400 IU/day of vitamin E given as prophylaxis to high risk women demonstrated a reduction in the risk of pre-eclampsia from 17 % in the control group to 8 % in the active treatment group . In this same double-masked r and omised controlled trial , women receiving vitamins C and E showed a reduction in biological markers of oxidative stress . Since this report , a number of multicentre r and omised clinical trials have been initiated both in low risk and in high risk population s , with the goal of testing the hypothesis that antioxidants reduce the incidence of pre-eclampsia ( Table 1 ) . In the UK , a multicentre trial is currently recruiting pregnant women with diabetes . The NIH has funded two antioxidant trials , one that is under way in Brazil and the second that is being conducted among nulliparous women in the NICHD Maternal Fetal Medicine Network . The International Trial of Antioxidants for the Prevention of Preeclampsia ( INTAPP ) , funded by the Canadian Institutes of Health Research , is enrolling nulliparas without additional risk factors ( Stratum I ) and multiparas and nulliparas with clinical risk factors for gestational hypertension ( Stratum II ) . Collectively , these trials should provide an answer to the question of the role of antioxidants in the prevention of pre-eclampsia and its related disorders . Recently , a meta- analysis of 19 clinical trials of  vitamin E  , for the most part secondary prevention trials , conducted in elderly population s at increased risk for a number of diseases ranging from lung or gastrointestinal cancer to cardiovascular disease , Alzheimer ’s disease or cataract , was published in the Annals of Internal Medicine . The authors of the meta- analysis concluded that high doses of vitamin E may be associated with an increased risk of all-cause mortality . What are the implication s of this meta- analysis for the ongoing pre-eclampsia prevention trials ? It is the responsibility of the Principal Investigators , the Steering Committees and Data Safety Monitoring Committees ( DSMC ) of ongoing clinical trials to take into account information generated from studies that arise in the course of their trial . They must assess the quality of the new evidence and determine how this information influences the balance of risks to benefits of the ongoing trials . In the case of the Canadian trial , both the DSMC and the hospital Ethics Committee have review ed the information and made their recommendations to the trial Steering Committee . The following is our evaluation of the quality of the evidence of the meta- analysis by Miller et al. , and its implication s for ongoing clinical trials of antioxidants in the prevention of pre-eclampsia Background : Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anemia . Vitamin E is a fat-soluble antioxidant that plays a central role in reducing lipid peroxidation and inhibiting the generation of reactive oxygen species . The aim of this cross-over r and omized study was to compare the effects of a vitamin E-coated polysulfone ( Vit E PS ) membrane and a non-vitamin E-coated polysulfone ( PS ) membrane on inflammatory markers and resistance to erythropoietin-stimulating agents ( ESAs ) . Methods : After a 1-month run-in period of st and ard bicarbonate dialysis with a synthetic membrane , 62 patients of both genders , and older than 18 years , dialysis vintage 48 ± 27 months , BMI 22 ± 3 ( from 13 different dialysis units ) were r and omized ( A-B or B-A ) in a cross-over design to Vit E PS ( treatment A ) and to PS ( treatment B ) both for 6 months . C-reactive protein ( CRP ) and interleukin-6 ( IL-6 ) concentrations were determined by a s and wich enzyme immunoassay at baseline and every 2 months ; red blood cell count , ESA dose and ESA resistance index ( ERI ) were assessed monthly . Results : Hemoglobin ( Hb ) levels significantly increased in the Vit E PS group from 11.1 ± 0.6 g/dl at baseline to 11.5 ± 0.7 at 6 months ( p < 0.001 ) and remained unchanged in the PS group . Although ESA dosage remained stable during the observation periods in both groups , ERI was significantly reduced in the Vit E PS group from 10.3 ± 2.2 IU-dl/kg/g Hb week at baseline to 9.2 ± 1.7 at 6 months ( p < 0.001 ) . No significant variation of ERI was observed in the PS group . A significant reduction in plasma CRP and IL-6 levels was observed in the Vit E PS  group : CRP from 6.7 ± 4.8 to 4.8 ± 2.2 mg/l ( p < 0.001 ) and IL-6 from 12.1 ± 1.4 to 7.5 ± 0.4 pg/ml ( p < 0.05 ) . In the PS group , CRP varied from 6.2 ± 4.0 to 6.4 ± 3.7 , and IL-6 from 10.6 ± 2.1 to 9.6 ± 3.5 ( p = n.s . ) . Conclusions : Treatment with Vit E PS membranes seems to lead to a reduction in ESA dosage in HD patients ; in addition , a low chronic inflammatory response may contribute to a sparing effect on exogenous ESA requirements BACKGROUND Oxidant stress has a pathogenic role in uremic anemia , possibly interfering with erythropoietin ( EPO ) function and red blood cell ( RBC ) survival . Therefore , it is expected that antioxidant therapy might exert a beneficial effect on these parameters . METHODS To test this hypothesis , we investigated some oxidant stress indices , anemia levels , and RBC survival in 47 hemodialysis ( HD ) patients r and omly assigned to three groups . Patients in groups A ( n = l8 ) and B ( n = 20 ) were on dialysis therapy using conventional cellulosic and synthetic membranes and were administered high and low doses of recombinant human EPO ( rHuEPO ) , respectively . Patients in group C ( n = 9 ) were dialyzed with vitamin E-modified membranes ( CL-Es ) and investigated in a two-step prospect i ve study . In step Cl , patients were administered rHuEPO doses similar to those of group A. In step C2 , rHuEPO doses were reduced to those of group B. As oxidant stress markers , we determined in plasma the susceptibility of lipids to undergo iron-catalyzed oxidation ( reactive oxygen molecules [ ROMs ] test ) and malondialdehyde-4-hydroxynonenal ( MDA-4HNE ) , alpha-tocopherol ( alpha-T ) , total thiol ( -SH ) , and total antioxidant activity . RBC survival was measured using the chromium 51 T/2 technique in 22 patients . RESULTS Results show that : ( 1 ) high rHuEPO doses ( groups A and C1 ) were associated with decreased ROM production , low alpha-T levels , and slightly increased -SH levels compared with corresponding groups on low rHuEPO doses ( groups B and C2 ) ; ( 2 ) treatment with CL-Es ( group C ) increased plasma alpha-T and decreased -SH levels ; these data were associated with decreased indices of lipid peroxidation , particularly MDA-4HNE 1evels , only in patients administered low rHuEPO doses ; ( 3 ) alpha-T concentration influenced RBC survival , which was remarkably decreased in HD patients ; patients treated with CL-Es showed a better degree of anemia correction ; and ( 4 ) alpha-T level correlated negatively with -SH level and seemed to be independent of the extent of peroxidation and oxidizability of plasma lipids . CONCLUSION Both EPO and CL-E can influence plasma antioxidants and , to an extent , lipid peroxidation processes . However , this study shows that even in patients treated with low rHuEPO doses , RBC survival close to normal and sufficient correction of anemia are achieved only when appropriate alpha-T levels are reached Exposure to environmental tobacco smoke ( ETS ) has been linked to increased risk of lung cancer and cardiovascular diseases in nonsmokers . Current research suggests that some of these diseases are associated with elevated oxidative stress . We investigated the effect of antioxidant ( AO ) intervention on the lipid peroxidation biomarker F2-isoprostanes ( F2-IsoPs ) , an index of oxidative stress , in plasma of nonsmokers exposed to ETS ( passive smokers).We measured free F2-IsoP concentrations in plasma of 67 passive smokers at baseline and after 2 mo of daily intervention with AOs or placebo .  The study subjects ( 47 females , 20 males ; mean age 46 ± 15 ) were r and omized into one of three treatment groups : vitamin C , " mixture " ( vitamin C , vitamin E , and α-lipoic-acid ) , and placebo . Investigated confounders included plasma baseline AO levels , lipid and total cholesterol profiles , transferrin saturation , and C-reactive protein . Plasma F2IsoP concentrations of subjects in the vitamin C and mixture groups decreased significantly by 17.2 pmol/l ( P = 0.0105 ) and 19.2 pmol/l ( P = 0.0083 ) when compared with the placebo group ( 11.4 % and 12.7 % , respectively ) . Daily AO supplementation ( especially with vitamin C ) decreases this oxidative stress biomarker in passive smokers . This finding might be of importance for the prevention of ETS-associated adverse health effects in nonsmokers The high incidence of cardiovascular disease in hemodialyzed ( HD ) patients is well established and oxidative stress has been involved in this phenomenon . The aim of our study was to evaluate if a vitamin E-coated dialyzer could offer protection to HD patients against oxidative stress . Sixteen HD patients were successively assessed for one month ( i ) on a high biocompatible synthetic dialyzer ( AN ) and ( ii ) on a vitamin E-coated dialyzer ( VE ) .  Blood sample s were taken before and after the dialysis session at the end of each treatment period . HD session conducted with the AN dialyzer was responsible for acute oxidative stress , significantly assessed after HD by a decreased plasma vitamin C level and an increased ascorbyl free radical (AFR)/vitamin C ratio used as an index of oxidative stress . Plasma elastase activity , reflecting neutrophil activation , was also increased ; soluble P-selectin , reflecting platelet activation , did not show any variation . The use of the VE dialyzer was associated with a less extended oxidative stress compared with the AN membrane : basal vitamin C level was higher , and after the HD session AFR/vitamin C ratio and elastase activity were not significantly increased . Plasma vitamin E levels were not affected . Our study demonstrates that HD is associated with oxidative stress , which can be partially prevented by the use of a vitamin E-coated dialyzer . Our data suggest that this dialyzer may exert a site-specific scavenging effect on free radical species in synergy with a reduced activation of neutrophils Background —Conjugated linoleic acids ( CLAs ) , a group of fatty acids shown to have beneficial effects in animals , are also used as weight loss supplements . Recently , we reported that the t 10 c 12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms . The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance . Methods and Results —In a double-blind placebo-controlled trial , 60 men with metabolic syndrome were r and omized to one of 3 groups receiving t 10 c 12 CLA , a CLA mixture , or placebo for 12 weeks . Insulin sensitivity ( euglycemic clamp ) , serum lipids , in vivo lipid peroxidation ( determined as urinary 8-iso-PGF2&agr ; [ F2-isoprostanes ] ) , 15-ketodihydro PGF2&agr ; , plasma vitamin E , plasma C-reactive protein , tumor necrosis factor-&agr ; , and interleukin-6 were assessed before and after treatment . Supplementation with t 10 c 12 CLA markedly increased 8-iso-PGF2&agr ; ( 578 % ) and C-reactive protein ( 110 % ) compared with placebo ( P < 0.0001 and P < 0.01 , respectively ) and independent of changes in hyperglycemia or dyslipidemia . The increases in 8-iso-PGF2&agr ; , but not in C-reactive protein , were significantly and independently related to aggravated insulin resistance . Oxidative stress was related to increased vitamin E levels , suggesting a compensatory mechanism . Conclusions —t 10 c 12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men . The oxidative stress seems closely related to induced insulin resistance , suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance . These unfavorable effects of t 10 c 12 CLA might be of clinical importance with regard to cardiovascular disease , in consideration of the widespread use of dietary supplements containing this fatty acid Cardiovascular disease represents the most common cause for the excess of morbidity and mortality found in end-stage renal disease ( ESRD ) and has prompted the exploration of multiple approaches to improve outcomes in these patients . Cardiovascular risk factors such as increased oxidative stress ( OxSt ) and inflammation are found in ESRD patients . A vitamin E-coated dialyzer using polysulfone membranes has been suggested to have positive effects on these factors . This 1-year study evaluated in 25 ESRD patients under chronic dialysis , the effects of a vitamin E-coated membrane ( VitabranE ViE ) " ex vivo " on mononuclear cells , OxSt , and inflammation-related biochemical and molecular biology markers using a molecular biology approach . p22(phox ) , heme oxygenase (HO)-1 , plasminogen activator inhibitor (PAI)-1 protein level , and phosphorylated extracellular signal-regulated kinase (pERK)1/2 status were evaluated at the beginning of the study , after 6 months and after 12 months by Western blot analysis and oxidized low-density lipoprotein ( OxLDL ) plasma level by enzyme-linked immunosorbent assay , alongside vascular remodeling assessment as measured by carotid intima-media thickness ( IMT ) in a subgroup of nine r and omly selected patients . p22(phox ) , PAI-1 , OxLDL , and pERK all decreased with VitabranE use , while HO-1 increased . Carotid IMT did not increase . Treatment with VitabranE significantly decreases the expression of proteins and markers relevant to OxSt and inflammation tightly associated with cardiovascular disease , and it appears highly likely that VitabranE use will provide a benefit in terms of cardiovascular protection BACKGROUND In the present prospect i ve , controlled , observational cohort study , we investigated the effects of the use of a vitamin E-coated membrane dialyser ( VEM ) on markers of chronic inflammation , oxidative stress and endothelial cell apoptosis in end-stage renal disease ( ESRD ) patients on chronic haemodialysis ( HD )  , as long as evidence of their effects on these pathogenetic routes are inconclusive as yet , despite their use for the last several years . METHODS Thirty-five stable ESRD patients underwent HD with the use of VEM for 6 months . Another 25 age- and sex-matched ESRD patients , being dialysed with conventional dialysers , served as controls . In both patient groups , beyond complete haematology and biochemistry work-up , serum CRP , apolipoproteins A1 and B , lipoprotein ( a ) ( Lp(a ) ) , hsIL-6 , MCP-1 , sICAM-1 , sVCAM-1 , sE-selectin , sFas and sFasL as well as plasma oxLDL , TBARS and TAS levels were determined at baseline and at 6 months of the study . RESULTS In the VEM group at 6 months , a significant reduction in CRP ( P = 0.004 ) , IL-6 ( P = 0.004 ) and sICAM-1 ( P = 0.04 ) levels was observed compared with baseline , along with a remarkable change in all markers of oxidative stress , i.e. increase in TAS ( P = 0.005 ) and decrease in TBARS ( P = 0.04 ) and oxLDL ( P < 0.001 ) . No significant changes were noted in the other parameters studied in the VEM group or in any parameter studied in the controls . Between the groups , significant differences were found in the change of CRP ( P = 0.001 ) , sICAM-1 ( P = 0.03 ) and oxLDL ( P = 0.04 ) compared with baseline . CONCLUSIONS HD with the use of VEM result ed in a significant reduction in inflammation and oxidative stress markers . Larger prospect i ve r and omized studies will need to confirm the findings of the present observational study Epilepsy is known as one of the most frequent neurological diseases , characterized by an enduring predisposition to generate epileptic seizures . Oxidative stress is believed to directly participate in pathways leading to neurodegeneration , which serves as the most important propagating factor , leading to the epileptic condition and cognitive decline . Moreover , there is also a growing body of evidence showing the disturbance of antioxidant system balance and consequently increased production of reactive species in patients with epilepsy . A meta- analysis , conducted in the present review confirms an association between epilepsy and increased lipid peroxidation . Furthermore , it was also shown that some of the antiepileptic drugs could potentially be responsible for additionally increased lipid peroxidation . Therefore , it is reasonable to propose that during the epileptic process neuroprotective treatment with antioxidants could lead to less sever structural damages , reduced epileptogenesis and milder cognitive deterioration . To evaluate this hypothesis studies investigating the neuroprotective therapeutic potential of various antioxidants in cells , animal seizure models and patients with epilepsy have been review ed . Numerous beneficial effects of  antioxidants on oxidative stress markers and in some cases also neuroprotective effects were observed in animal seizure models . However , despite these encouraging results , till now only a few antioxidants have been further applied to patients with epilepsy as an add-on therapy . Based on the several positive findings in animal models , a strong need for more carefully planned , r and omized , double-blind , cross-over , placebo-controlled clinical trials for the evaluation of  antioxidants efficacy in patients with epilepsy is warranted Free radicals in cigarette smoke ( CS ) cause oxidative damage to proteins , DNA , and lipids , contributing to the pathobiology of atherosclerosis , heart disease , and cancer . In vitro studies have shown that antioxidants quench free radicals and ameliorate certain aspects of biomolecular damage caused by CS . It is hypothesized that a combination of antioxidants is more effective than a single antioxidant , due to their interactions . To investigate whether supplemental antioxidants reduce CS-related lipid peroxidation in vivo and whether they are more effective in combination , we conducted an intervention study in smokers . In a r and omized double-blind placebo-controlled trial , we investigated whether vitamin C or an antioxidant mixture containing vitamin C , alpha-lipoic acid , and vitamin E decreases plasma F(2)-isoprostane levels , an index of oxidant stress , in smokers . Plasma of 126 smokers ( mean age , 46 years ; age range , 20 - 78 years ) was analyzed for F(2)-isoprostanes at baseline and after intervention with antioxidants and placebo . In smokers with a body mass index ( BMI ) above the median , 2 months of daily supplementation with 500 mg of vitamin C decreased plasma F(2)-isoprostane levels by 28.8 pmol/liter when compared with the placebo group ( P = 0.001 ) ; levels in the mixture group were 7.45 pmol/liter lower after treatment , but this difference was not statistically significant ( P = 0.14 ) . There was no treatment effect in smokers with a low BMI .  BMI was significantly positively associated with plasma F(2)-isoprostane levels ( trend P = 0.001 ) . Antioxidants decrease smoking-related lipid peroxidation markers of oxidative stress in humans with high BMI . Our results do not indicate that an antioxidant combination is more effective than vitamin C alone . The intake of antioxidants may help prevent smoking-related diseases . Smoking cessation should still be considered the most effective way to prevent smoking-related diseases OBJECTIVE Vitamin C is a powerful antioxidant that is potentially useful in the prevention of atherosclerosis in diabetic individuals . However , the mechanism(s ) of vitamin C 's anti-atherosclerotic effects in vivo are unresolved , and clinical trials in nondiabetic individuals have yielded conflicting results . Therefore , we performed 32 studies in a r and omized , crossover , dose-response trial in 8 volunteers with type 2 diabetes to determine the effects of vitamin C on serum vitamin C levels , lipids , inflammation , and coagulation . METHODS Well-controlled , type 2 volunteers received , in r and omized order for 2-week periods , each of the following : 1 ) no supplemental vitamin C , 2 ) low-dose vitamin C ( 250 mg/day ) , 3 ) medium-dose vitamin C ( 500 mg/day ) , and 4 ) high-dose vitamin C ( 1,000 mg/day ) . A high-caloric content lunch was ingested during each study arm to enhance oxidative stress . Serum vitamin C levels and atherosclerotic risk factors including lipids and markers of oxidative stress , inflammation , and hypercoagulation were determined . RESULTS Serum vitamin C levels increased significantly at all dosages . In addition , the high-caloric content meal result ed in acute elevations of glucose , insulin , and triglycerides for several hours postmeal . However , no significant effect of vitamin C was observed on lipid parameters or any of the surrogate markers of oxidative stress , inflammation , or hypercoagulability . CONCLUSION Our study suggests that if vitamin C does have anti-atherosclerotic effects in diabetes , it does not exert them through the traditional pathways identifiable by established surrogate markers of cardiovascular risk In the last few years haemodiafiltration with on-line regeneration of ultrafiltrate ( HFR ) has been shown to have a positive impact on inflammation and oxidative stress biomarkers , but its effect on antioxidant levels and on oxidative damage to biomolecules in the long-term is still unknown . This is a r and omised clinical study over 12 months involving 40 patients on haemodialysis , comparing the effect of HFR ( n = 25 ) dialysis with haemodialysis with polysulfone ( HD-PS , n = 15 ) on oxidative stress . Total antioxidant capacity , enzymatic antioxidant [ superoxide dismutase ( SOD ) , catalase and glutathione peroxidase ] , non-enzymatic ( GSH ) and biomarkers of oxidative stress ( TBARs , carbonyl groups and 8-OH-dG ) were evaluated . The antioxidant activity decreased in the lymphocytes of patients dialysed with HFR , with a significant decrease in the enzyme SOD . In the oxidative stress biomarkers , an increase was seen in the levels of 8-OH-dG in patients on HD-PS dialysis but not in those treated with HFR . Throughout the year the changes in antioxidant levels and biomarkers of oxidative damage in patients dialysed with HFR were generally more modest and fluctuated less than those dialysed with HD-PS . Our study indicates that , in general , long-term dialysis with HFR does not modified antioxidant parameters or increases the oxidative damage to biomolecules . The HFR showed to be a biocompatible technique for long-term dialysis BACKGROUND AND AIMS Pre- clinical studies suggest that sesame and its lignans induce beneficial changes in risk factors related to cardiovascular disease and increase the bioavailability of mammalian lignans . However , only very few intervention trials have investigated the potential bioactivities of sesame in humans . We aim ed to investigate the effects of sesame supplementation in humans on blood lipids , blood pressure , systemic oxidative stress , inflammatory biomarkers and mammalian lignan metabolism . METHODS AND RESULTS We conducted a r and omized , placebo-controlled cross-over intervention trial at a university research centre . Overweight or obese men and women ( n=33 ) consumed 25g/d of sesame ( approximately 50mg/d of sesame lignan ) and an iso-caloric placebo matched for macronutrient composition for 5 wks each . Each intervention period was preceded by a 4-wk washout period . Blood lipid profiles , day time ambulatory blood pressure , oxidative stress and inflammatory biomarkers and urinary mammalian lignans were measured before and after each intervention . Results are presented as the effect of sesame supplementation relative to placebo .  Urinary excretion of the mammalian lignans , enterolactone and enterodiol , increased by approximately 8-fold ( P<0.001 ) . Blood lipids and blood pressure were not altered . In addition , markers of systemic inflammation ( C-reactive protein , interleukin-6 , tumor necrosis factor-alpha ) and lipid peroxidation ( F(2)-isoprostanes ) were not affected . CONCLUSION Supplementation with 25g/d of sesame can significantly increase the exposure to mammalian lignans . However , this did not cause any improvement in markers of cardiovascular disease risk in overweight or obese men and women AIM In patients with end-stage renal disease ( ESRD ) cardiovascular morbidity and mortality are increased . Apart from traditional and uremia-specific factors oxidative stress has been implicated as a main risk factor . This study investigated the influence of two different high-flux hemodialysis membranes on parameters of oxidative stress during a dialysis session . PATIENTS AND METHODS 14 stable ESRD patients were enrolled in the study and r and omly assigned to high-flux hemodialysis using either a polyamide membrane ( Polyflux 14 ; PA group ) or a new polysulfone membrane ( Diacap Polysulfone HI PS 15 ; PS group ) . All patients received 6 treatments with the same membrane . During the 5th treatment parameters of dialysis efficiency , biocompatibility ( cell counts , complement C3a , thrombin-antithrombin complex ) and oxidative stress ( lipid peroxides , total antioxidative capacity ) were measured . RESULTS Parameters of dialysis efficiency and biocompatibility were similar in both treatment groups . At the beginning of the dialysis session both groups showed a low to moderate level of oxidative stress and a reduced total antioxidative capacity as compared to healthy controls . Both parameters deteriorated significantly during the extracorporeal procedure with a similar magnitude in both membrane groups . No correlation between oxidative or antioxidative capacity and parameters of biocompatibility or dialysis efficiency could be found . CONCLUSIONS Dialysis with synthetic high-flux membranes induces a temporary deterioration of oxidative stress parameters in ESRD patients despite good dialysis efficiency and biocompatibility Purpose of review To review recent publications concerning the epidemiology and management of cardiovascular disease in the stages of chronic kidney disease . Recent findings Chronic kidney disease is a state of increased risk for atherosclerotic and cardiomyopathic disease . The mechanisms of cardiovascular disease probably change with the different stages of chronic kidney disease . Both proteinuria and decreased glomerular filtration rate are probably independent cardiovascular disease risk factors , although the impact of the latter is modest . Traditional risk factors are important predictors of cardiovascular disease in chronic kidney disease . Recent r and omized controlled trials and cohort studies have supported interventions for smoking cessation , blood pressure control , renin – angiotensin system blockade , the correction of lipid abnormalities , and utilizing antiplatelet agents . Some uraemia-related risk factors predict the development of cardiovascular disease , particularly hypoalbuminaemia , inflammation , anaemia , and homocysteinaemia . However , r and omized controlled trials of anaemia correction and of an increased quantity of dialysis were negative . Summary The role of oxidant stress , divalent ion abnormalities , various lipid abnormalities and other potential factors require further investigation . To determine whether these uraemia-related factors are markers of cardiovascular disease risk or are actually cardiotoxic requires additional r and omized controlled trials The oxidation hypothesis of atherogenesis has been the focus of much research over the past 2 decades . However , r and omized placebo-controlled trials evaluating the efficacy of vitamin E in preventing cardiovascular events in aggregate have failed to show a beneficial effect . Implicit in these trials is that the dose of vitamin E tested effectively suppressed oxidative stress status but this was never determined . We defined the dose-dependent effects of vitamin E ( RRR-alpha-tocopherol ) to suppress plasma concentrations of F2-isoprostanes , a biomarker of free radical-mediated lipid peroxidation , in participants with polygenic hypercholesterolemia and enhanced oxidative stress , a population at risk for cardiovascular events . A time-course study was first performed in participants supplemented with 3200 IU/day of vitamin E for 20 weeks . A dose-ranging study was then performed in participants supplemented with 0 , 100 , 200 , 400 , 800 , 1600 , or 3200 IU/day of vitamin E for 16 weeks . In the time-course study , maximum suppression of plasma F2-isoprostane concentrations did not occur until 16 weeks of supplementation . In the dose-ranging study there was a linear trend between the dosage of  vitamin E and percentage reduction in plasma F2-isoprostane concentrations which reached significance at doses of 1600 IU ( 35+/-2 % , p<0.035 ) and 3200 IU ( 49+/-10 % , p<0.005 ) . This study provides information on the dosage of vitamin E that decreases systemic oxidant stress in vivo in humans and informs the planning and evaluation of clinical studies that assess the efficacy of vitamin E to mitigate disease
The conversion of dialysis patients to a vitamin E-coated dialyser is associated with an improvement in circulating biomarkers of lipid peroxidation , which is of potential clinical benefit
BACKGROUND Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anaemia .
We conducted a systematic review and meta- analysis to examine the effect of Excebrane , a vitamin E-coated cellulose-based dialyser , on circulating biomarkers of lipid peroxidation , as surrogate markers of oxidative stress .