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: The British Regional Heart Study ( BRHS ) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol ( HDLC ) and incidence of coronary heart disease was eliminated by covariance adjustment . Using the proportional hazards model and adjusting for age , blood pressure , smoking , body mass index , and low-density lipoprotein cholesterol , we analyzed this relation separately in the Framingham Heart Study ( FHS ) , Lipid Research Clinics Prevalence Mortality Follow-up Study ( LRCF ) and Coronary Primary Prevention Trial ( CPPT ) , and Multiple Risk Factor Intervention Trial ( MRFIT ) . In CPPT and MRFIT ( both r and omized trials in middle-age high-risk men ) , only the control groups were analyzed . A 1-mg/dl ( 0.026 mM ) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2 % in men ( FHS , CPPT , and MRFIT ) and 3 % in women ( FHS ) . In LRCF , where only fatal outcomes were documented , a 1-mg/dl increment in HDLC was associated with significant 3.7 % ( men ) and 4.7 % ( women ) decrements in cardiovascular disease mortality rates . The 95 % confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably , and all contained the range 1.9 - 2.9 % . HDLC levels were essentially unrelated to non-cardiovascular disease mortality . When differences in analytic methodology were eliminated , a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies Human plasma platelet-activating factor acetylhydrolase ( PAF-AH ) is a phospholipase A2 that is primarily associated with low density lipoprotein ( LDL ) . PAF-AH activity has also been found in high density lipoprotein ( HDL ) , although it has recently been indicated that there is no PAF-AH protein in HDL . Plasma paraoxonase 1 ( PON1 ) is an HDL-associated esterase , which also exhibits PAF-AH – like activity . The effect of atorvastatin ( 20 mg per day for 4 months ) on PAF-AH and PON1 activities in patients with dyslipidemia of type IIA ( n=55 ) or type IIB ( n=21 ) was studied . In both patient groups , atorvastatin significantly reduced plasma PAF-AH activity because of the decrease in LDL plasma levels and the preferential decrease in PAF-AH activity on dense LDL subfractions ( LDL-4 and LDL-5 ) . Drug therapy did not affect HDL-associated PAF-AH activity or serum PON1 activities toward paraoxon and phenylacetate in either patient group . However , because of the reduction in LDL cholesterol levels , the ratios of HDL-associated PAF-AH and serum PON1 activities to LDL cholesterol levels were significantly increased after drug administration . The reduction of the LDL-associated PAF-AH activity and the elevation in the ratios of HDL-associated PAF-AH and PON1 activities to LDL plasma levels may represent a new dimension in the antiatherogenic effect of atorvastatin Objective —Diminished serum paraoxonase and arylesterase activities ( measures of paraoxonase-1 [ PON-1 ] function ) in humans have been linked to heightened systemic oxidative stress and atherosclerosis risk . The clinical prognostic use of measuring distinct PON-1 activities has not been established , and the genetic determinants of PON-1 activities are not known . Methods and Results —We established analytically robust high-throughput assays for serum paraoxonase and arylesterase activities and measured these in 3668 stable subjects undergoing elective coronary angiography without acute coronary syndrome and were prospect ively followed for major adverse cardiovascular events ( MACE= death , myocardial infa rct ion , stroke ) over 3 years . Low serum arylesterase and paraoxonase activities were both associated with increased risk for MACE , with arylesterase activity showing greatest prognostic value ( quartile 4 versus quartile 1 ; hazard ratio 2.63 ; 95 % CI , 1.97–3.50 ; P<0.01 ) . Arylesterase remained significant after adjusting for traditional risk factors , C-reactive protein , and creatinine clearance ( hazard ratio , 2.20 ; 95 % CI , 1.60–3.02 ; P<0.01 ) , predicted future development of MACE in both primary and secondary prevention population s , and reclassified risk categories incrementally to traditional clinical variables . A genome-wide association study identified distinct single nucleotide polymorphisms within the PON-1 gene that were highly significantly associated with serum paraoxonase ( 1.18 × 10 - 303 ) or arylesterase ( 4.99 × 10−116 ) activity but these variants were not associated with either 3-year MACE risk in an angiographic cohort ( n=2136 ) or history of either coronary artery disease or myocardial infa rct ion in the Coronary Artery Disease Genome-Wide Replication and Meta- Analysis consortium ( n≈80 000 subjects ) . Conclusion —Diminished serum arylesterase activity , but not the genetic determinants of PON-1 functional measures , provides incremental prognostic value and clinical reclassification of stable subjects at risk of developing MACE CONTEXT AND OBJECTIVE Paraoxonase 1 ( PON1 ) , an enzyme associated with high-density lipoprotein ( HDL-PON1 ) , is reported to have antioxidant and cardioprotective properties . The aim of the present study was to investigate the effects of anthocyanins on the HDL-PON1 activity and cholesterol efflux capacity in hypercholesterolemic subjects . DESIGN AND PARTICIPANTS A total of 122 hypercholesterolemic subjects were given 160 mg of anthocyanins twice daily or placebo ( n = 61 of each group ) for 24 weeks in a double-blind , r and omized , placebo-controlled trial . Participants and investigators were masked to treatment allocation . RESULTS Anthocyanin consumption significantly increased HDL cholesterol and decreased low -density lipoprotein cholesterol concentrations compared with placebo ( P < .018 and P < .001 , respectively ) . Anthocyanin supplementation also increased the activity of HDL-PON1 compared with placebo ( P < .001 ) . Furthermore , cholesterol efflux capacity was increased more in the anthocyanin group ( 20.0 % increase ) than in the placebo group ( 0.2 % increase ) ( P < .001 ) . The negative correlations established between HDL-PON1 activity and the levels of lipid hydroperoxides associated with HDL confirm the relationship between PON1 activity and lipid peroxidation of lipoproteins . Furthermore , a strong positive correlation was noted between increased HDL-PON1 activity and improved cholesterol efflux capacity both before and after adjustment for HDL cholesterol and apolipoprotein AI in anthocyanin-treated subjects ( both P < .001 ) . Inhibition of HDL-PON1 activity strongly prevented the antioxidant ability of HDL and attenuated the cholesterol efflux capacity of subjects from anthocyanin group . CONCLUSIONS Our observations suggest that the alterations of PON1 activity by anthocyanin observed in hypercholesterolemic HDL reflect a shift to an improvement of cholesterol efflux capacity of HDL and may provide a link between anthocyanin and cardioprotective effects Type 2 diabetes ( T2D ) is associated with increased oxidative stress as indicated by elevated levels of lipid peroxidation and protein oxidation products . Since reactive oxygen species ( ROS ) can cause damage to biological macromolecules including DNA , this study investigated oxidative damage to DNA using the alkaline ( pH > 13 ) comet assay in peripheral whole blood leukocytes sample d from 15 dyslipidemic T2D patients treated with simvastatin ( 20 mg/day ) , 15 dyslipidemic T2D patients not treated with simvastatin , 20 non‐dyslipidemic T2D patients , and 20 healthy individuals ( controls ) . Our results showed a greater DNA migration in terms of damage index ( DI ) ( p < 0.01 ) in the dyslipidemic T2D patients not treated with statin ( DI = 67.70 ± 10.89 ) when compared to the dyslipidemic T2D patients under statin treatment ( DI = 47.56 ± 7.02 ) , non‐dyslipidemic T2D patients ( DI = 52.25 ± 9.14 ) , and controls ( DI = 13.20 ± 6.40 ) . Plasma malondialdehyde ( MDA ) and C‐reactive protein ( CRP ) levels were also increased and total antioxidant reactivity ( TAR ) and paraoxonase activity ( PON1 ) decreased in non‐dyslipidemic T2D patients and dyslipidemic T2D non‐treated with simvastatin . We also found that DI was inversely correlated with TAR ( r = −0.61 , p < 0.05 ) and PON1 ( r = −0.67 , p < 0.01 ) . In addition , there was a significant positive correlation between DI and CRP ( r = 0.80 , p < 0.01 ) . Our results therefore indicate that simvastatin treatment plays a protective role on oxidative damage to DNA in dyslipidemic T2D patients probably reflecting a general decrease in oxidative stress in these patients . Copyright © 2010 John Wiley & Sons , BACKGROUND AND STUDY AIMS The prevalence of non-alcoholic fatty liver disease ( NAFLD ) appears to be increasing . The aim of the present study was to investigate the relationship between hepatic antioxidant paraoxonase 1 ( PON1 ) activity , lipid peroxidation and antioxidant enzymes in patients with NAFLD and the effect of atorvastatin . PATIENTS AND METHODS This study was conducted on 50 patients with NAFLD and 20 normal subjects matched for age and sex . All of them were subjected to the following investigations : abdominal ultrasonography , serum PON1 activity level , liver function tests , serum lipid profile , fasting and postpr and ial blood glucose and serum levels of malondialdehyde ( MDA ) and glutathione peroxidase ( GP ) .  NAFLD patients were further r and omly classified into two groups ( 25 patients each ) , groups Ia and Ib . Only group Ia received atorvastatin 40 mg tablet for 8months . RESULTS Obesity , dyslipidaemia and impaired glucose tolerance were prevalent in group I. There was a significant decrease in serum PON1 activity with a significant increase in MDA and GP activity ( i.e. , there is a significant increase in lipid peroxidation rate ) in group I compared with group II . After atorvastatin therapy , there was a significant increase in serum PNO1 activity and significant decrease in serum MDA levels . CONCLUSION Patients with NAFLD show enhanced oxidative stress which may lead to non-alcoholic steatohepatitis ( NASH ) . Reduced PON1 activity and increased MDA could be considered a biochemical marker for lipid peroxidation , which require follow-up in patients with NAFLD . Atorvastatin may have a role in prevention of , or delay , the transformation of liver steatosis into NASH 1 Patients with advanced chronic renal disease and anaemia have decreased serum paraoxonase‐1 ( PON1 ) activity and an increased degree of oxidative stress compared with normal subjects . The present study investigated the effects of treatment of anaemia with exogenous recombinant erythropoietin ( EPO ) β and iron on levels of antibodies against oxidized low‐density lipoproteins ( ox‐LDL ) , as well as on serum PON1 activity and concentration , in predialysis patients with chronic renal disease . 2 Forty‐nine patients with chronic renal failure and haemoglobin ( Hb ) < 11 g/dL were treated over a period of 6 months with EPOβ ( 80–120 U/kg per week , s.c . ) and variable doses of iron . Selected biochemical variables were determined before and after treatment . 3 Treatment with EPOβ and iron was associated with a significant increase in mean ( ±SD ) blood Hb concentration compared with pretreatment values ( 12.8 ± 1.5 vs 9.9 ± 0.6 g/dL , respectively ; P < 0.001 ) . The average dose of EPOβ was 6160 ± 3000 U/week . After 6 months of treatment , compared with pretreatment values , the median levels ( 95 % confidence intervals ) of antibodies against ox‐LDL were decreased ( 17.5 ( 10.6–24.4 ) vs 24.8 ( 11.5–38.1 ) U/mL , respectively ; P < 0.001 ) , serum PON1 activity was slightly but significantly increased ( 123.6 ( 76.1–343.6 ) vs 101.0 ( 50.0–332.5 ) U/L , respectively ; P = 0.016 ) and the concentration of PON1 was significantly decreased ( 37.3 ( 11.8– 
    Output:
    
agent
RESULTS Meta- analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities , but not PON1 protein concentration .
The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose , treatment duration and changes in plasma low-density lipoprotein cholesterol concentration .
CONCLUSION The increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes
***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: The British Regional Heart Study ( BRHS ) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol ( HDLC ) and incidence of coronary heart disease was eliminated by covariance adjustment . Using the proportional hazards model and adjusting for age , blood pressure , smoking , body mass index , and low-density lipoprotein cholesterol , we analyzed this relation separately in the Framingham Heart Study ( FHS ) , Lipid Research Clinics Prevalence Mortality Follow-up Study ( LRCF ) and Coronary Primary Prevention Trial ( CPPT ) , and Multiple Risk Factor Intervention Trial ( MRFIT ) . In CPPT and MRFIT ( both r and omized trials in middle-age high-risk men ) , only the control groups were analyzed . A 1-mg/dl ( 0.026 mM ) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2 % in men ( FHS , CPPT , and MRFIT ) and 3 % in women ( FHS ) . In LRCF , where only fatal outcomes were documented , a 1-mg/dl increment in HDLC was associated with significant 3.7 % ( men ) and 4.7 % ( women ) decrements in cardiovascular disease mortality rates . The 95 % confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably , and all contained the range 1.9 - 2.9 % . HDLC levels were essentially unrelated to non-cardiovascular disease mortality . When differences in analytic methodology were eliminated , a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies Human plasma platelet-activating factor acetylhydrolase ( PAF-AH ) is a phospholipase A2 that is primarily associated with low density lipoprotein ( LDL ) . PAF-AH activity has also been found in high density lipoprotein ( HDL ) , although it has recently been indicated that there is no PAF-AH protein in HDL . Plasma paraoxonase 1 ( PON1 ) is an HDL-associated esterase , which also exhibits PAF-AH – like activity . The effect of atorvastatin ( 20 mg per day for 4 months ) on PAF-AH and PON1 activities in patients with dyslipidemia of type IIA ( n=55 ) or type IIB ( n=21 ) was studied . In both patient groups , atorvastatin significantly reduced plasma PAF-AH activity because of the decrease in LDL plasma levels and the preferential decrease in PAF-AH activity on dense LDL subfractions ( LDL-4 and LDL-5 ) . Drug therapy did not affect HDL-associated PAF-AH activity or serum PON1 activities toward paraoxon and phenylacetate in either patient group . However , because of the reduction in LDL cholesterol levels , the ratios of HDL-associated PAF-AH and serum PON1 activities to LDL cholesterol levels were significantly increased after drug administration . The reduction of the LDL-associated PAF-AH activity and the elevation in the ratios of HDL-associated PAF-AH and PON1 activities to LDL plasma levels may represent a new dimension in the antiatherogenic effect of atorvastatin Objective —Diminished serum paraoxonase and arylesterase activities ( measures of paraoxonase-1 [ PON-1 ] function ) in humans have been linked to heightened systemic oxidative stress and atherosclerosis risk . The clinical prognostic use of measuring distinct PON-1 activities has not been established , and the genetic determinants of PON-1 activities are not known . Methods and Results —We established analytically robust high-throughput assays for serum paraoxonase and arylesterase activities and measured these in 3668 stable subjects undergoing elective coronary angiography without acute coronary syndrome and were prospect ively followed for major adverse cardiovascular events ( MACE= death , myocardial infa rct ion , stroke ) over 3 years . Low serum arylesterase and paraoxonase activities were both associated with increased risk for MACE , with arylesterase activity showing greatest prognostic value ( quartile 4 versus quartile 1 ; hazard ratio 2.63 ; 95 % CI , 1.97–3.50 ; P<0.01 ) . Arylesterase remained significant after adjusting for traditional risk factors , C-reactive protein , and creatinine clearance ( hazard ratio , 2.20 ; 95 % CI , 1.60–3.02 ; P<0.01 ) , predicted future development of MACE in both primary and secondary prevention population s , and reclassified risk categories incrementally to traditional clinical variables . A genome-wide association study identified distinct single nucleotide polymorphisms within the PON-1 gene that were highly significantly associated with serum paraoxonase ( 1.18 × 10 - 303 ) or arylesterase ( 4.99 × 10−116 ) activity but these variants were not associated with either 3-year MACE risk in an angiographic cohort ( n=2136 ) or history of either coronary artery disease or myocardial infa rct ion in the Coronary Artery Disease Genome-Wide Replication and Meta- Analysis consortium ( n≈80 000 subjects ) . Conclusion —Diminished serum arylesterase activity , but not the genetic determinants of PON-1 functional measures , provides incremental prognostic value and clinical reclassification of stable subjects at risk of developing MACE CONTEXT AND OBJECTIVE Paraoxonase 1 ( PON1 ) , an enzyme associated with high-density lipoprotein ( HDL-PON1 ) , is reported to have antioxidant and cardioprotective properties . The aim of the present study was to investigate the effects of anthocyanins on the HDL-PON1 activity and cholesterol efflux capacity in hypercholesterolemic subjects . DESIGN AND PARTICIPANTS A total of 122 hypercholesterolemic subjects were given 160 mg of anthocyanins twice daily or placebo ( n = 61 of each group ) for 24 weeks in a double-blind , r and omized , placebo-controlled trial . Participants and investigators were masked to treatment allocation . RESULTS Anthocyanin consumption significantly increased HDL cholesterol and decreased low -density lipoprotein cholesterol concentrations compared with placebo ( P < .018 and P < .001 , respectively ) . Anthocyanin supplementation also increased the activity of HDL-PON1 compared with placebo ( P < .001 ) . Furthermore , cholesterol efflux capacity was increased more in the anthocyanin group ( 20.0 % increase ) than in the placebo group ( 0.2 % increase ) ( P < .001 ) . The negative correlations established between HDL-PON1 activity and the levels of lipid hydroperoxides associated with HDL confirm the relationship between PON1 activity and lipid peroxidation of lipoproteins . Furthermore , a strong positive correlation was noted between increased HDL-PON1 activity and improved cholesterol efflux capacity both before and after adjustment for HDL cholesterol and apolipoprotein AI in anthocyanin-treated subjects ( both P < .001 ) . Inhibition of HDL-PON1 activity strongly prevented the antioxidant ability of HDL and attenuated the cholesterol efflux capacity of subjects from anthocyanin group . CONCLUSIONS Our observations suggest that the alterations of PON1 activity by anthocyanin observed in hypercholesterolemic HDL reflect a shift to an improvement of cholesterol efflux capacity of HDL and may provide a link between anthocyanin and cardioprotective effects Type 2 diabetes ( T2D ) is associated with increased oxidative stress as indicated by elevated levels of lipid peroxidation and protein oxidation products . Since reactive oxygen species ( ROS ) can cause damage to biological macromolecules including DNA , this study investigated oxidative damage to DNA using the alkaline ( pH > 13 ) comet assay in peripheral whole blood leukocytes sample d from 15 dyslipidemic T2D patients treated with simvastatin ( 20 mg/day ) , 15 dyslipidemic T2D patients not treated with simvastatin , 20 non‐dyslipidemic T2D patients , and 20 healthy individuals ( controls ) . Our results showed a greater DNA migration in terms of damage index ( DI ) ( p < 0.01 ) in the dyslipidemic T2D patients not treated with statin ( DI = 67.70 ± 10.89 ) when compared to the dyslipidemic T2D patients under statin treatment ( DI = 47.56 ± 7.02 ) , non‐dyslipidemic T2D patients ( DI = 52.25 ± 9.14 ) , and controls ( DI = 13.20 ± 6.40 ) . Plasma malondialdehyde ( MDA ) and C‐reactive protein ( CRP ) levels were also increased and total antioxidant reactivity ( TAR ) and paraoxonase activity ( PON1 ) decreased in non‐dyslipidemic T2D patients and dyslipidemic T2D non‐treated with simvastatin . We also found that DI was inversely correlated with TAR ( r = −0.61 , p < 0.05 ) and PON1 ( r = −0.67 , p < 0.01 ) . In addition , there was a significant positive correlation between DI and CRP ( r = 0.80 , p < 0.01 ) . Our results therefore indicate that simvastatin treatment plays a protective role on oxidative damage to DNA in dyslipidemic T2D patients probably reflecting a general decrease in oxidative stress in these patients . Copyright © 2010 John Wiley & Sons , BACKGROUND AND STUDY AIMS The prevalence of non-alcoholic fatty liver disease ( NAFLD ) appears to be increasing . The aim of the present study was to investigate the relationship between hepatic antioxidant paraoxonase 1 ( PON1 ) activity , lipid peroxidation and antioxidant enzymes in patients with NAFLD and the effect of atorvastatin . PATIENTS AND METHODS This study was conducted on 50 patients with NAFLD and 20 normal subjects matched for age and sex . All of them were subjected to the following investigations : abdominal ultrasonography , serum PON1 activity level , liver function tests , serum lipid profile , fasting and postpr and ial blood glucose and serum levels of malondialdehyde ( MDA ) and glutathione peroxidase ( GP ) .  NAFLD patients were further r and omly classified into two groups ( 25 patients each ) , groups Ia and Ib . Only group Ia received atorvastatin 40 mg tablet for 8months . RESULTS Obesity , dyslipidaemia and impaired glucose tolerance were prevalent in group I. There was a significant decrease in serum PON1 activity with a significant increase in MDA and GP activity ( i.e. , there is a significant increase in lipid peroxidation rate ) in group I compared with group II . After atorvastatin therapy , there was a significant increase in serum PNO1 activity and significant decrease in serum MDA levels . CONCLUSION Patients with NAFLD show enhanced oxidative stress which may lead to non-alcoholic steatohepatitis ( NASH ) . Reduced PON1 activity and increased MDA could be considered a biochemical marker for lipid peroxidation , which require follow-up in patients with NAFLD . Atorvastatin may have a role in prevention of , or delay , the transformation of liver steatosis into NASH 1 Patients with advanced chronic renal disease and anaemia have decreased serum paraoxonase‐1 ( PON1 ) activity and an increased degree of oxidative stress compared with normal subjects . The present study investigated the effects of treatment of anaemia with exogenous recombinant erythropoietin ( EPO ) β and iron on levels of antibodies against oxidized low‐density lipoproteins ( ox‐LDL ) , as well as on serum PON1 activity and concentration , in predialysis patients with chronic renal disease . 2 Forty‐nine patients with chronic renal failure and haemoglobin ( Hb ) < 11 g/dL were treated over a period of 6 months with EPOβ ( 80–120 U/kg per week , s.c . ) and variable doses of iron . Selected biochemical variables were determined before and after treatment . 3 Treatment with EPOβ and iron was associated with a significant increase in mean ( ±SD ) blood Hb concentration compared with pretreatment values ( 12.8 ± 1.5 vs 9.9 ± 0.6 g/dL , respectively ; P < 0.001 ) . The average dose of EPOβ was 6160 ± 3000 U/week . After 6 months of treatment , compared with pretreatment values , the median levels ( 95 % confidence intervals ) of antibodies against ox‐LDL were decreased ( 17.5 ( 10.6–24.4 ) vs 24.8 ( 11.5–38.1 ) U/mL , respectively ; P < 0.001 ) , serum PON1 activity was slightly but significantly increased ( 123.6 ( 76.1–343.6 ) vs 101.0 ( 50.0–332.5 ) U/L , respectively ; P = 0.016 ) and the concentration of PON1 was significantly decreased ( 37.3 ( 11.8– 
    Output:
    