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: Objective . To evaluate the effects of ezetimibe/simvastatin ( EZE/SIMV ) and rosuvastatin ( ROSUV ) on oxidative stress ( OS ) markers in patients with diabetic polyneuropathy ( DPN ) . Methods . We performed a r and omized , double-blind , placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus ( T2DM ) and DPN , as evaluated by composite scores and nerve conduction studies ( NCS ) . Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo , EZE/SIMV 10/20 mg , or ROSUV 20 mg for 16 weeks . All patients were assessed before and after treatment : primary outcomes were lipid peroxidation ( LPO ) , and nitric oxide ( NO ) surrogate levels in plasma ; secondary outcomes included NCS , neuropathic symptom scores , and metabolic parameters . Data were expressed as mean ± SD or SEM , frequencies , and percentages ; we used nonparametric analysis . Results . LPO levels were reduced in both statin arms after 16 weeks of treatment ( p < 0.05 versus baseline ) , without changes in the placebo group . NO levels were not significantly affected by statin treatment , although a trend towards significance concerning increased NO levels was noted in both statin arms . No significant changes were observed for the NCS or composite scores . Discussion . EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy . This trial is registered with NCT02129231 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 Lipid-lowering therapy has been reported to reduce several oxidative stress ( OS ) markers in hypercholesterolemia . Since OS is frequently associated with renal dysfunction , we aim ed to investigate the effect of hypolipidemic drugs on oxidative stress and plasma taurine ( Tau ) , a sulfur amino acid with a marked antioxidant effect , in chronic kidney disease ( CKD ) . We enrolled 30 CKD r and omized to receive three different hypolipidemic regimens for 12 months : simvastatin alone ( 40 mg/day ) or ezetimibe/simvastatin combined therapy ( 10/20 or 10/40 mg/day ) .  Low molecular weight ( LMW ) thiols including homocysteine , cysteine , cysteinylglycine , glutathione , and glutamylcysteine in their reduced and total form and oxidative stress indices as malondialdehyde ( MDA ) and allantoin/uric acid ( All/UA ) ratio were also evaluated . Tau concentration significantly increased throughout the therapy . The rise of taurine was more striking for the group with the concomitant administration of ezetimibe/simvastatin 10/40 mg/day ( + 31.6 % after 1 year of therapy ) . A significant decrease of both MDA and All/UA ratio was observed during therapy for all patients ( −19 % for both MDA and All/UA ratio ) with a more pronounced effect in patients treated with ezetimibe/simvastatin 10/40 mg/day ( −26 % for MDA and −28 % for All/UA ratio ) . Besides , an increase of thiols reduced forms was found ( + 20.7 % of LMW thiols redox status ) with a greater effect in subjects treated with ezetimibe/simvastatin 10/40 mg/day ( + 24.7 % ) . Moreover , we demonstrated that oxidative stress improvement during therapy was correlated with increased taurine levels . We hypothesize that taurine may be responsible for the oxidative stress improvement observed during lipid-lowering treatment through the reduction of superoxide anion production at the respiratory chain activity level 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 Abstract —Recent evidence suggests that some benefit from the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may occur independent of lipid lowering . We aim ed to determine the effect of simvastatin on coronary endothelial function , endothelial NO synthase ( eNOS ) expression , and oxidative stress in experimental hypercholesterolemia ( HC ) in the absence of cholesterol lowering . Pigs were r and omized to 3 experimental groups : normal diet ( N group ) , high cholesterol diet ( HC group ) , and HC diet with simvastatin ( HC+S group ) for 12 weeks . Low density lipoprotein cholesterol was similarly increased in the HC and HC+S groups compared with the N group . In vitro analysis of coronary large- and small-vessel endothelium-dependent vasorelaxation was performed . The mean vasorelaxation of epicardial vessels to bradykinin was significantly attenuated in the HC group compared with the N group ( 32.3±1.2 % versus 42.9±1.6 % , respectively;P < 0.0001 ) . This attenuation was significantly reversed in the HC+S group ( 38.7±1.5 % , P < 0.005 versus HC group ) . The maximal vasorelaxation to substance P was significantly attenuated in the HC group compared with the N group ( 50.5±11.9 % versus 79.3±5.3 % , respectively;P < 0.05 ) . This attenuated response was normalized in the HC+S group ( 74.9±4.1 % , P < 0.05 versus HC group ) . The maximal arteriolar vasorelaxation to bradykinin was also significantly attenuated in the HC group compared with the N group ( 71.9±4.9 % versus 96.8±1.34 % , respectively;P < 0.005 ) . This was reversed in the HC+S group ( 98.4±0.6 % , P < 0.0001 versus HC group ) . Western blotting of coronary tissue homogenates for eNOS demonstrated a decrease in protein levels in the HC group compared with the N group , with normalization in the HC+S group . Elevation of plasma F2-isoprostanes and thiobarbituric acid – reactive substances , markers of oxidative stress , occurred in the HC compared with the N group . These changes were reversed in the HC+S group . In summary , simvastatin preserves endothelial function in coronary epicardial vessels and arterioles in experimental HC ( in the absence of cholesterol lowering ) in association with an increase in coronary eNOS levels and a decrease in oxidative stress . These alterations may play a role in the reduction in cardiac events after treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors The aim of this study was to investigate the modulating effect of atorvastatin on serum paraoxonase 1 enzyme ( PON1 ) activity in type 2 diabetic Egyptian patients with or without nephropathy . The present study was carried out on the following groups : control group , which consisted of 30 healthy persons ; Group I , which consisted of 20 type 2 diabetic patients without nephropathy ; and Group II , which consisted of 20 type 2 diabetic patients with nephropathy . All the patients selected were under an antidiabetic regimen of insulin  , and patients receiving antihypertensive agents were excluded from the follow-up study to avoid drug interaction fallacies . Twenty-two patients ( 15 without nephropathy and seven with nephropathy ) received atorvastatin in individually adjusted oral dosage ( range 10 - 20 mg ) once per day for 12 weeks . All cases were subjected to thorough clinical examination and history taking and measurement of serum levels of PON1 activity , malondialdehyde ( MDA ) , glutathione reductase activity , fasting glucose , total cholesterol , triglycerides , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , urea , and creatinine . Urine sample s were collected for determination of proteinuria . The obtained results showed that PON1 activity and HDL significantly decreased and fasting glucose significantly increased in Group I and Group II when compared to the control group , with significant difference in their levels between Group II and Group I. MDA , total cholesterol , and LDL levels significantly increased and glutathione reductase activity significantly decreased in Group I and Group II when compared to the control group . Urea , creatinine , and proteinuria levels showed significant increase in Group II when compared to the control group and Group I , with nonsignificant difference between control group and Group I. Atorvastatin therapy caused a significant increase in PON1 activity , and serum levels of MDA and glutathione reductase activity were significantly decreased and increased , respectively . Also , total cholesterol , triglyceride and LDL-cholesterol levels were significantly reduced with a significant increase in HDL-cholesterol levels . There was a significant modest reduction in serum urea and creatinine levels as well as in proteinuria level . Fasting glucose level was significantly reduced under the antidiabetic regimen of insulin through the follow-up period . PON1 activity showed a significant negative correlation with glucose and LDL , and a significant positive correlation with HDL in all the studied groups . It could be concluded that atorvastatin with its pleiotropic effects could provide optimal therapeutic intervention to control not only dyslipidemia , but also oxidative stress status with consequent improvement in the course of type 2 diabetes and diabetic nephropathy . More specifically , restoration of PON1 activity by atorvastatin opens a window to investigate other drugs that could provide a new adjuvant therapeutic line for better control of diabetes and diabetic nephropathy . Further research is also recommended to study the distribution of PON1 genetic polymorphism among the Egyptian population to explain the variability in its activity and its relationship with 
    Output:
    
agent
Conclusions : This systematic review and meta- analysis showed that statin treatment significantly reduces systemic MDA concentrations .
***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: Objective . To evaluate the effects of ezetimibe/simvastatin ( EZE/SIMV ) and rosuvastatin ( ROSUV ) on oxidative stress ( OS ) markers in patients with diabetic polyneuropathy ( DPN ) . Methods . We performed a r and omized , double-blind , placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus ( T2DM ) and DPN , as evaluated by composite scores and nerve conduction studies ( NCS ) . Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo , EZE/SIMV 10/20 mg , or ROSUV 20 mg for 16 weeks . All patients were assessed before and after treatment : primary outcomes were lipid peroxidation ( LPO ) , and nitric oxide ( NO ) surrogate levels in plasma ; secondary outcomes included NCS , neuropathic symptom scores , and metabolic parameters . Data were expressed as mean ± SD or SEM , frequencies , and percentages ; we used nonparametric analysis . Results . LPO levels were reduced in both statin arms after 16 weeks of treatment ( p < 0.05 versus baseline ) , without changes in the placebo group . NO levels were not significantly affected by statin treatment , although a trend towards significance concerning increased NO levels was noted in both statin arms . No significant changes were observed for the NCS or composite scores . Discussion . EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy . This trial is registered with NCT02129231 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 Lipid-lowering therapy has been reported to reduce several oxidative stress ( OS ) markers in hypercholesterolemia . Since OS is frequently associated with renal dysfunction , we aim ed to investigate the effect of hypolipidemic drugs on oxidative stress and plasma taurine ( Tau ) , a sulfur amino acid with a marked antioxidant effect , in chronic kidney disease ( CKD ) . We enrolled 30 CKD r and omized to receive three different hypolipidemic regimens for 12 months : simvastatin alone ( 40 mg/day ) or ezetimibe/simvastatin combined therapy ( 10/20 or 10/40 mg/day ) .  Low molecular weight ( LMW ) thiols including homocysteine , cysteine , cysteinylglycine , glutathione , and glutamylcysteine in their reduced and total form and oxidative stress indices as malondialdehyde ( MDA ) and allantoin/uric acid ( All/UA ) ratio were also evaluated . Tau concentration significantly increased throughout the therapy . The rise of taurine was more striking for the group with the concomitant administration of ezetimibe/simvastatin 10/40 mg/day ( + 31.6 % after 1 year of therapy ) . A significant decrease of both MDA and All/UA ratio was observed during therapy for all patients ( −19 % for both MDA and All/UA ratio ) with a more pronounced effect in patients treated with ezetimibe/simvastatin 10/40 mg/day ( −26 % for MDA and −28 % for All/UA ratio ) . Besides , an increase of thiols reduced forms was found ( + 20.7 % of LMW thiols redox status ) with a greater effect in subjects treated with ezetimibe/simvastatin 10/40 mg/day ( + 24.7 % ) . Moreover , we demonstrated that oxidative stress improvement during therapy was correlated with increased taurine levels . We hypothesize that taurine may be responsible for the oxidative stress improvement observed during lipid-lowering treatment through the reduction of superoxide anion production at the respiratory chain activity level 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 Abstract —Recent evidence suggests that some benefit from the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may occur independent of lipid lowering . We aim ed to determine the effect of simvastatin on coronary endothelial function , endothelial NO synthase ( eNOS ) expression , and oxidative stress in experimental hypercholesterolemia ( HC ) in the absence of cholesterol lowering . Pigs were r and omized to 3 experimental groups : normal diet ( N group ) , high cholesterol diet ( HC group ) , and HC diet with simvastatin ( HC+S group ) for 12 weeks . Low density lipoprotein cholesterol was similarly increased in the HC and HC+S groups compared with the N group . In vitro analysis of coronary large- and small-vessel endothelium-dependent vasorelaxation was performed . The mean vasorelaxation of epicardial vessels to bradykinin was significantly attenuated in the HC group compared with the N group ( 32.3±1.2 % versus 42.9±1.6 % , respectively;P < 0.0001 ) . This attenuation was significantly reversed in the HC+S group ( 38.7±1.5 % , P < 0.005 versus HC group ) . The maximal vasorelaxation to substance P was significantly attenuated in the HC group compared with the N group ( 50.5±11.9 % versus 79.3±5.3 % , respectively;P < 0.05 ) . This attenuated response was normalized in the HC+S group ( 74.9±4.1 % , P < 0.05 versus HC group ) . The maximal arteriolar vasorelaxation to bradykinin was also significantly attenuated in the HC group compared with the N group ( 71.9±4.9 % versus 96.8±1.34 % , respectively;P < 0.005 ) . This was reversed in the HC+S group ( 98.4±0.6 % , P < 0.0001 versus HC group ) . Western blotting of coronary tissue homogenates for eNOS demonstrated a decrease in protein levels in the HC group compared with the N group , with normalization in the HC+S group . Elevation of plasma F2-isoprostanes and thiobarbituric acid – reactive substances , markers of oxidative stress , occurred in the HC compared with the N group . These changes were reversed in the HC+S group . In summary , simvastatin preserves endothelial function in coronary epicardial vessels and arterioles in experimental HC ( in the absence of cholesterol lowering ) in association with an increase in coronary eNOS levels and a decrease in oxidative stress . These alterations may play a role in the reduction in cardiac events after treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors The aim of this study was to investigate the modulating effect of atorvastatin on serum paraoxonase 1 enzyme ( PON1 ) activity in type 2 diabetic Egyptian patients with or without nephropathy . The present study was carried out on the following groups : control group , which consisted of 30 healthy persons ; Group I , which consisted of 20 type 2 diabetic patients without nephropathy ; and Group II , which consisted of 20 type 2 diabetic patients with nephropathy . All the patients selected were under an antidiabetic regimen of insulin  , and patients receiving antihypertensive agents were excluded from the follow-up study to avoid drug interaction fallacies . Twenty-two patients ( 15 without nephropathy and seven with nephropathy ) received atorvastatin in individually adjusted oral dosage ( range 10 - 20 mg ) once per day for 12 weeks . All cases were subjected to thorough clinical examination and history taking and measurement of serum levels of PON1 activity , malondialdehyde ( MDA ) , glutathione reductase activity , fasting glucose , total cholesterol , triglycerides , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , urea , and creatinine . Urine sample s were collected for determination of proteinuria . The obtained results showed that PON1 activity and HDL significantly decreased and fasting glucose significantly increased in Group I and Group II when compared to the control group , with significant difference in their levels between Group II and Group I. MDA , total cholesterol , and LDL levels significantly increased and glutathione reductase activity significantly decreased in Group I and Group II when compared to the control group . Urea , creatinine , and proteinuria levels showed significant increase in Group II when compared to the control group and Group I , with nonsignificant difference between control group and Group I. Atorvastatin therapy caused a significant increase in PON1 activity , and serum levels of MDA and glutathione reductase activity were significantly decreased and increased , respectively . Also , total cholesterol , triglyceride and LDL-cholesterol levels were significantly reduced with a significant increase in HDL-cholesterol levels . There was a significant modest reduction in serum urea and creatinine levels as well as in proteinuria level . Fasting glucose level was significantly reduced under the antidiabetic regimen of insulin through the follow-up period . PON1 activity showed a significant negative correlation with glucose and LDL , and a significant positive correlation with HDL in all the studied groups . It could be concluded that atorvastatin with its pleiotropic effects could provide optimal therapeutic intervention to control not only dyslipidemia , but also oxidative stress status with consequent improvement in the course of type 2 diabetes and diabetic nephropathy . More specifically , restoration of PON1 activity by atorvastatin opens a window to investigate other drugs that could provide a new adjuvant therapeutic line for better control of diabetes and diabetic nephropathy . Further research is also recommended to study the distribution of PON1 genetic polymorphism among the Egyptian population to explain the variability in its activity and its relationship with 
    Output:
    