human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Red blood cells and plasma reduced and oxidized glutathione levels , glutathione peroxidase ( GSH-Px ) activity , thiobarbituric acid reactants ( TBAR ) of both chronic ambulatory peritoneal dialysis ( CAPD ) patients and a matched control group were investigated in this study . Oxidized and reduced pyridinic nucleotides in red blood cells ( RBC ) , in which NADPH is a direct expression of hexose monophosphate shunt function , were also studied . The results obtained indicate that RBC and plasma are exposed to oxidative stress in CAPD . This condition is characterized by a decreased GSH/GSSG ratio , particularly evident in RBC as a consequence of the GSSG accumulation . Lipid peroxidation is increased , as indicated by raised TBAR levels , and reduced pyridinic nucleotides are decreased . Increased GSH-Px levels and unmodified or slightly increased GSH content were observed in the RBC but not in plasma , which showed decreased GSH and unmodified peroxidase activity . Peroxidase correlated positively with TBAR levels in the RBC lysates . In a subgroup of patients treated with erythropoietin ( vs. untreated patients and controls ) no differences were observed in the glutathione-related parameters studied . These data suggest that a mechanism for adaptation to oxidative conditions may be present in CAPD and its effects on RBC integrity are discussed in comparison with the hemodialysis conditions previously studied 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 BACKGROUND  Asymmetric dimethylarginine ( ADMA ) is an endogenous inhibitor of nitric oxide synthase and an independent predictor of overall mortality and cardiovascular outcome in haemodialysis ( HD ) patients . In the present study , we compared the effects of a vitamin E-coated polysulfone membrane ( PSE ) and a non-vitamin E-coated polysulfone membrane ( PS ) on oxidative stress markers such as ADMA . METHODS Thirty-one HD patients were enrolled to this investigation . They were allocated into two groups : in the PSE group ( n = 16 ) , PSE was used for 6 months , followed by PS for an additional 12 months ; in the PS group ( n = 15 ) , PS was used for the entire observation period . Plasma ADMA , oxidized low density lipoprotein ( Ox-LDL ) and malondialdehyde LDL ( MDA-LDL ) levels were measured at baseline , 3 , 6 , 12 and 18 months . Plasma ADMA in peritoneal dialysis ( PD ) patients and in healthy individuals was also measured . RESULTS Predialysis concentrations of ADMA ( 0.72+/- 0.13 nmol/ml ) were significantly higher in the HD group than in both PD patients ( 0.63+/-0.10 nmol/ml , P<0.01 ) and healthy individuals ( 0.44+/-0.01 nmol/ml , P<0.0001 ) . Treatment with PSE for 6 months significantly reduced predialysis levels of ADMA ( 0.54+/-0.09 nmol/ml ) compared with baseline ( 0.74+/-0.12 nmol/ml ; P<0.01 ) . Predialysis levels of Ox-LDL and MDA-LDL after 6 months therapy with PSE were also significantly lower than baseline values . Treatment with PS subsequent to treatment with PSE again increased ADMA , Ox-LDL and MDA-LDL back to baseline levels . In the PS group , ADMA , Ox-LDL and MDA-LDL levels remained unchanged during the entire treatment period of 18 months . CONCLUSIONS We confirmed that use of PSE reduced ADMA that had accumulated in HD patients . This finding indicates that PSE exerts anti-oxidant activity . A r and omized controlled study will be required to determine whether PSE prevents cardiovascular diseases and other dialysis-related complications by reducing oxidative stress 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 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 Intravenous iron application to anemic patients on hemodialysis leads to an " oversaturation " of transferrin . As a result , non-transferrin-bound , redox-active iron might induce lipid peroxidation . To test the hypothesis that vitamin E attenuates lipid peroxidation in patients receiving 100 mg of iron(III ) hydroxide sucrose complex intravenously during a hemodialysis session , 22 patients were investigated in a r and omized cross-over design , either with or without a single oral dose of 1200 IU of all-rac-alpha-tocopheryl acetate taken 6 h before the hemodialysis session . Blood was drawn before and 30 , 60 , 90 , 135 , and 180 min after the start of the iron infusion , and areas under the curve ( AUC0 - 180 min ) of ratios of plasma malondialdehyde ( MDA ) to cholesterol and plasma total peroxides to cholesterol ( two markers of lipid peroxidation ) were determined as the outcome variables . At baseline of the session without vitamin E supplementation , plasma alpha-tocopherol concentrations ( 27.6 + /- 1.8 micromol/L ) and ratios of alpha-tocopherol to cholesterol ( 5.88 + /- 1.09 mmol/mol ) were normal , plasma MDA concentrations were above normal ( 1.20 + /- 0.28 micromol/ L ) , and bleomycin-detectable iron ( BDI ) , indicating the presence of redox-active iron , was not detectable . Upon iron infusion , BDI and MDA concentrations increased significantly ( P < 0.001 ) . BDI concentrations explained the increase over baseline in MDA concentrations ( MDA = 1.29 + /- 0.075 x BDI ) . Vitamin E supplementation , leading to a 68 % increase in plasma alpha-tocopherol concentrations , significantly reduced the AUC0 - 180 min of MDA to cholesterol ( P = 0.004 ) and peroxides to cholesterol ( P = 0.002 ) . These data demonstrate that a single oral dose of vitamin E attenuates lipid peroxidation in patients on hemodialysis receiving intravenous iron .  Given that intravenous iron is applied repeatedly to patients on hemodialysis , this therapeutic approach may protect against oxidative stress-related degenerative disease in the long term BACKGROUND Excess cardiovascular mortality has been documented in chronic haemodialysis patients . Oxidative stress is greater in haemodialysis patients with prevalent cardiovascular disease than in those without , suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysis . We investigated the effect of high-dose vitamin E supplementation on cardiovascular disease outcomes in haemodialysis patients with pre-existing cardiovascular disease . METHODS Haemodialysis patients with pre-existing cardiovascular disease ( n=196 ) aged 40 - 75 years at baseline from six dialysis centres were enrolled and r and omised to receive  800 IU/day vitamin E or matching placebo . Patients were followed for a median 519 days . The primary endpoint was a composite variable consisting of : myocardial infa rct ion ( fatal and non-fatal ) , ischaemic stroke , peripheral vascular disease 
    Output:
    
agent
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
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Red blood cells and plasma reduced and oxidized glutathione levels , glutathione peroxidase ( GSH-Px ) activity , thiobarbituric acid reactants ( TBAR ) of both chronic ambulatory peritoneal dialysis ( CAPD ) patients and a matched control group were investigated in this study . Oxidized and reduced pyridinic nucleotides in red blood cells ( RBC ) , in which NADPH is a direct expression of hexose monophosphate shunt function , were also studied . The results obtained indicate that RBC and plasma are exposed to oxidative stress in CAPD . This condition is characterized by a decreased GSH/GSSG ratio , particularly evident in RBC as a consequence of the GSSG accumulation . Lipid peroxidation is increased , as indicated by raised TBAR levels , and reduced pyridinic nucleotides are decreased . Increased GSH-Px levels and unmodified or slightly increased GSH content were observed in the RBC but not in plasma , which showed decreased GSH and unmodified peroxidase activity . Peroxidase correlated positively with TBAR levels in the RBC lysates . In a subgroup of patients treated with erythropoietin ( vs. untreated patients and controls ) no differences were observed in the glutathione-related parameters studied . These data suggest that a mechanism for adaptation to oxidative conditions may be present in CAPD and its effects on RBC integrity are discussed in comparison with the hemodialysis conditions previously studied 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 BACKGROUND  Asymmetric dimethylarginine ( ADMA ) is an endogenous inhibitor of nitric oxide synthase and an independent predictor of overall mortality and cardiovascular outcome in haemodialysis ( HD ) patients . In the present study , we compared the effects of a vitamin E-coated polysulfone membrane ( PSE ) and a non-vitamin E-coated polysulfone membrane ( PS ) on oxidative stress markers such as ADMA . METHODS Thirty-one HD patients were enrolled to this investigation . They were allocated into two groups : in the PSE group ( n = 16 ) , PSE was used for 6 months , followed by PS for an additional 12 months ; in the PS group ( n = 15 ) , PS was used for the entire observation period . Plasma ADMA , oxidized low density lipoprotein ( Ox-LDL ) and malondialdehyde LDL ( MDA-LDL ) levels were measured at baseline , 3 , 6 , 12 and 18 months . Plasma ADMA in peritoneal dialysis ( PD ) patients and in healthy individuals was also measured . RESULTS Predialysis concentrations of ADMA ( 0.72+/- 0.13 nmol/ml ) were significantly higher in the HD group than in both PD patients ( 0.63+/-0.10 nmol/ml , P<0.01 ) and healthy individuals ( 0.44+/-0.01 nmol/ml , P<0.0001 ) . Treatment with PSE for 6 months significantly reduced predialysis levels of ADMA ( 0.54+/-0.09 nmol/ml ) compared with baseline ( 0.74+/-0.12 nmol/ml ; P<0.01 ) . Predialysis levels of Ox-LDL and MDA-LDL after 6 months therapy with PSE were also significantly lower than baseline values . Treatment with PS subsequent to treatment with PSE again increased ADMA , Ox-LDL and MDA-LDL back to baseline levels . In the PS group , ADMA , Ox-LDL and MDA-LDL levels remained unchanged during the entire treatment period of 18 months . CONCLUSIONS We confirmed that use of PSE reduced ADMA that had accumulated in HD patients . This finding indicates that PSE exerts anti-oxidant activity . A r and omized controlled study will be required to determine whether PSE prevents cardiovascular diseases and other dialysis-related complications by reducing oxidative stress 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 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 Intravenous iron application to anemic patients on hemodialysis leads to an " oversaturation " of transferrin . As a result , non-transferrin-bound , redox-active iron might induce lipid peroxidation . To test the hypothesis that vitamin E attenuates lipid peroxidation in patients receiving 100 mg of iron(III ) hydroxide sucrose complex intravenously during a hemodialysis session , 22 patients were investigated in a r and omized cross-over design , either with or without a single oral dose of 1200 IU of all-rac-alpha-tocopheryl acetate taken 6 h before the hemodialysis session . Blood was drawn before and 30 , 60 , 90 , 135 , and 180 min after the start of the iron infusion , and areas under the curve ( AUC0 - 180 min ) of ratios of plasma malondialdehyde ( MDA ) to cholesterol and plasma total peroxides to cholesterol ( two markers of lipid peroxidation ) were determined as the outcome variables . At baseline of the session without vitamin E supplementation , plasma alpha-tocopherol concentrations ( 27.6 + /- 1.8 micromol/L ) and ratios of alpha-tocopherol to cholesterol ( 5.88 + /- 1.09 mmol/mol ) were normal , plasma MDA concentrations were above normal ( 1.20 + /- 0.28 micromol/ L ) , and bleomycin-detectable iron ( BDI ) , indicating the presence of redox-active iron , was not detectable . Upon iron infusion , BDI and MDA concentrations increased significantly ( P < 0.001 ) . BDI concentrations explained the increase over baseline in MDA concentrations ( MDA = 1.29 + /- 0.075 x BDI ) . Vitamin E supplementation , leading to a 68 % increase in plasma alpha-tocopherol concentrations , significantly reduced the AUC0 - 180 min of MDA to cholesterol ( P = 0.004 ) and peroxides to cholesterol ( P = 0.002 ) . These data demonstrate that a single oral dose of vitamin E attenuates lipid peroxidation in patients on hemodialysis receiving intravenous iron .  Given that intravenous iron is applied repeatedly to patients on hemodialysis , this therapeutic approach may protect against oxidative stress-related degenerative disease in the long term BACKGROUND Excess cardiovascular mortality has been documented in chronic haemodialysis patients . Oxidative stress is greater in haemodialysis patients with prevalent cardiovascular disease than in those without , suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysis . We investigated the effect of high-dose vitamin E supplementation on cardiovascular disease outcomes in haemodialysis patients with pre-existing cardiovascular disease . METHODS Haemodialysis patients with pre-existing cardiovascular disease ( n=196 ) aged 40 - 75 years at baseline from six dialysis centres were enrolled and r and omised to receive  800 IU/day vitamin E or matching placebo . Patients were followed for a median 519 days . The primary endpoint was a composite variable consisting of : myocardial infa rct ion ( fatal and non-fatal ) , ischaemic stroke , peripheral vascular disease 
    Output:
    