***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: Recent studies have shown that passive smoking impairs vascular endothelial function and induces oxidative stress in humans . However , in most of the previous human data regarding tobacco-induced pathophysiology , vascular endothelial dysfunction and oxidative stress have been separately assessed . This study was design ed to determine the association between the acute effect of passive smoking on vascular endothelial function and in-vivo oxidative stress status . We studied 30 healthy male Japanese volunteers ( 32 + /- 7 years ) including 15 habitual smokers and 15 nonsmokers . After baseline echocardiographic , hemodynamic recording , and blood sampling , subjects were exposed to passive smoking for 30 min . Endothelium-dependent vasodilation was measured by using % flow-mediated vasodilation ( % FMD ) of the brachial artery and plasma levels of 8-isoprostane was measured by enzyme immunoassay before and after the passive smoking exposure . Baseline % FMD was lower ( 4.3 % + /- 1.2 % vs. 10.9 % + /- 3.1 % , p < 0.001 ) and baseline plasma 8-isoprostane level was higher ( 41.5 + /- 5.8 pg/mL vs. 26.9 + /- 5.4 pg/mL , p < 0.001 ) in smokers than those in nonsmokers . The % FMD and 8-isoprostane level did not change after passive smoking in smokers . In nonsmokers , however , the % FMD decreased ( to 5.0 % + /- 1.9 % , p < 0.001 ) and the 8-isoprostane level increased ( to 37.8 + /- 9.6 pg/mL , p < 0.001 ) significantly after 30 min passive smoking exposure , equivalently to the levels of smokers . Sixty corrected sample s before and after passive smoking exposure in all patients showed a significant negative correlation between the % FMD and the plasma 8-isoprostane levels ( n = 60 , r = -0.69 , p < 0.001 ) . Even 30 min of passive smoking rapidly impairs vascular endothelial function , which is associated with oxidative stress . Our data provide the pathophysiological insight for the recent epidemiological evidence about the increased risk of coronary heart disease among nonsmokers exposed to passive smoking Female sex hormones have been implicated in the cardioprotection of premenopausal women . However , the cardiovascular actions of these hormones and the effects of their natural fluctuations during the menstrual cycle are not fully understood . We studied changes in vascular function during the menstrual cycle in 15 healthy premenopausal women . Four noninvasive procedures were performed during the early follicular ( EF ) , late follicular ( LF ) , early luteal ( EL ) , and late luteal ( LL ) phases : flow-mediated dilatation ( FMD ) of the brachial artery during reactive hyperemia , laser Doppler velocimetry ( LDV ) with direct current iontophoresis of acetylcholine ( ACh ) and nitroprusside , whole body arterial compliance ( WBAC ) , and pulse wave velocity . Hormone levels were consistent with predicted cycle phase and showed that all subjects ovulated during the cycle studied . FMD , LDV with ACh , and WBAC varied cyclically , with significant increases from the F to LF phase , sharp falls in the EL phase , and significant recoveries in the LL phase . These changes were most marked for FMD [ EF , 8.8 + /- 0.6 % ( mean + /- SEM ) ; LF , 10.0 + /- 0.7 ; EL , 4.2 + /- 0.6 ; LL , 8.6 + /- 0.9 ] and the LDV response to ACh ( EF , 2.7 + /- 0.2 V/min ; LF , 3.3 + /- 0.4 ; EL , 1.8 + /- 0.3 ; LL , 2.7 + /- 0.4 ) . WBAC changed similarly ( EF , 0.58 + /- 0.08 arbitrary units ; LF , 0.84 + /- 0.06 ; EL , 0.65 + /- 0.05 ; LL , 0.68 + /- 0.06 ) . Sodium nitroprusside-induced vasodilatation decreased significantly from EF to EL , with no other significant difference , and pulse wave velocity did not vary significantly over the four time points . Conductance and resistance artery endothelial reactivity and smooth muscle sensitivity to nitric oxide and arterial compliance are modulated significantly in response to the changing hormonal patterns of the menstrual cycle . These findings emphasize the importance of menstrual phase in the interpretation of data on endothelial function and may provide insights into the mechanisms underlying sex differences in cardiovascular risk and other disease processes in premenopausal women Background Normalization of brachial artery flow-mediated dilation ( FMD ) to individual shear stress area under the curve ( peak FMD : SSAUC ratio ) has recently been proposed as an approach to control for the large inter-subject variability in reactive hyperemia-induced shear stress ; however , the adoption of this approach among research ers has been slow . The present study was design ed to further examine the efficacy of FMD normalization to shear stress in reducing measurement variability . Methods Five different magnitudes of reactive hyperemia-induced shear stress were applied to 20 healthy , physically active young adults ( 25.3 ± 0 . 6 yrs ; 10 men , 10 women ) by  manipulating forearm cuff occlusion  duration : 1 , 2 , 3 , 4 , and 5 min , in a r and omized order . A venous blood draw was performed for determination of baseline whole blood viscosity and hematocrit . The magnitude of occlusion-induced forearm ischemia was quantified by dual-wavelength near-infrared spectrometry ( NIRS )  . Brachial artery diameters and velocities were obtained via high-resolution ultrasound . The SSAUC was individually calculated for the duration of time-to-peak dilation . Results One-way repeated measures ANOVA demonstrated distinct magnitudes of occlusion-induced ischemia ( volume and peak ) , hyperemic shear stress , and peak FMD responses ( all p < 0.0001 ) across forearm occlusion duration s. Differences in peak FMD were abolished when normalizing FMD to SSAUC ( p = 0.785 ) . Conclusion Our data confirm that normalization of FMD to SSAUC eliminates the influences of variable shear stress and solidifies the utility of FMD : SSAUC ratio as an index of endothelial function Background Mental stress has been linked to increased morbidity and mortality in coronary artery disease and to atherosclerosis progression . Experimental studies have suggested that damage to the endothelium may be an important mechanism . Methods and Results Endothelial function was studied in 10 healthy men ( aged 50.4±9.6 years ) and in 8 non – insulin-dependent diabetic men ( aged 52.0±7.2 years ) . Brachial artery flow-mediated dilation ( FMD , endothelium dependent ) and response to 50 & mgr;g of sublingual glyceryl trinitrate ( GTN , endothelium independent ) were measured noninvasively by use of high-resolution ultrasound before and after ( 30 , 90 , and 240 minutes ) a st and ardized mental stress test . The same protocol without mental stress was repeated on a separate occasion in the healthy men . In healthy subjects , FMD ( 5.0±2.1 % ) was significantly ( P < 0.01 ) reduced at 30 and 90 minutes after mental stress ( 2.8±2.3 % and 2.3±2.4 % , respectively ) and returned toward normal after 4 hours ( 4.1±2.0 % ) . Mental stress had no effect on the response to GTN . In the repeated studies without mental stress , FMD did not change . The diabetic subjects had lower FMD than did the control subjects ( 3.0±1.5 % versus 5.0±2.1 % , respectively;P = 0.02 ) but showed no changes in FMD ( 2.7±1.1 % after 30 minutes , 2.8±1.9 % after 90 minutes , and 3.1±2.3 % after 240 minutes ) or GTN responses after mental stress . Conclusions These findings suggest that brief episodes of mental stress , similar to those encountered in everyday life , may cause transient ( up to 4 hours ) endothelial dysfunction in healthy young individuals . This might represent a mechanistic link between mental stress and atherogenesis OBJECTIVES The aims of this study were to determine whether chronic or acute impairment of flow mediated vasodilation ( FMD ) in the brachial artery of smokers can be restored or preserved by the antioxidant vitamin E. BACKGROUND Transient impairment of endothelial function after heavy cigarette smoking and chronic endothelial dysfunction in smokers result at least in part from increased oxidative stress . METHODS We studied 22 healthy male smokers ( mean + /- SD , 23 + /- 9 cigarettes per day ) r and omly assigned to receive either 600 IU vitamin E per day ( n = 11 , age 28 + /- 6 years ) or placebo ( n = 11 , age 27 + /- 6 years ) for four weeks and 11 age-matched healthy male nonsmokers .  Flow mediated vasodilation and endothelium-independent , nitroglycerin-induced dilation were assessed in the brachial artery using high resolution ultrasound ( 7.5 MHz ) at baseline and after therapy . Subjects stopped smoking 2 h before the ultrasound examinations . At the end of the treatment period , a third scan was obtained 20 min after smoking a cigarette ( 0.6 mg nicotine , 7 mg tar ) to estimate transient impairment of FMD . RESULTS Flow mediated vasodilation at baseline was abnormal in the vitamin E ( 5.3 + /- 3.8 , p < 0.01 ) and in the placebo group ( 6.4 + /- 3.5 , p < 0.05 ) compared with nonsmoking controls ( 11.6 + /- 4.7 ) . Using a two-way repeated measures analysis of variance ( ANOVA ) to examine the effects of vitamin E on FMD , we found no effect for the grouping factor ( p = 0.5834 ) in the ANOVA over time but a highly significant difference with respect to time ( p = 0.0065 ) . The interaction of the time factor and the grouping factor also proved to be significant ( p = 0.0318 ) . Flow mediated vasodilation values remained similar after treatment for four weeks in both groups but declined faster after smoking a cigarette in subjects taking placebo compared with those receiving vitamin E ( p values from successive differences for the time/group factor : 0.0001/0.0017 ) . The transient attenuation of FMD ( calculated as the percent change in FMD ) was related to the improvement of the antioxidant status , estimated as percent changes in thiobarbituric acid-reactive substances ( r = -0.67 , p = 0.0024 ) . Nitroglycerin-induced dilation did not differ between study groups at baseline or after therapy . CONCLUSIONS These results demonstrate that oral supplementation of vitamin E can attenuate transient impairment of endothelial function after heavy smoking due to an improvement of the oxidative status but can not restore chronic endothelial dysfunction within four weeks in healthy male smokers In light of the current method ological developments in flow-mediated dilation ( FMD ) testing and the recognition that oxidative stress may play an important role in regulating this process , the present study sought to : ( 1 ) compare flow-mediated dilation ( FMD ) following 5 and 10 min of forearm cuff occlusion , and ( 2 ) evaluate the role of oxidative stress on vasodilation , both distal and proximal to the cuff . Of the 14 subjects studied , 6 partook solely in a validation study of the antioxidant cocktail ( AOC ; vitamins C , E , and α-lipoic acid ) , while the remaining 8 subjects underwent  FMD assessment in response to 5 and 10 min of forearm occlusion following ingestion of AOC or placebo . Although the efficacy of the AOC was clearly documented by elevated plasma ascorbate levels ( ~95 % ) and a reduced free radical concentration ( ~65 % ) , no effects of acute oral antioxidants were observed . FMD was significantly augmented in response to 10 min of forearm occlusion when compared to 5 min , whether expressed as % change ( 10.1 ± 2 vs. 4.5 ± 1 % , respectively ) or absolute change in diameter ( 0.035 ± 0.005 vs. 0.018 ± 0.005 cm , respectively ) . Additionally , post-occlusion shear rate ( 28,640 ± 2,799 vs. 18,629 ± 1,724/s , AUC ) , FMD/shear rate ( ~50 % ) , and time to peak dilation ( 68 ± 7 vs. 53 ± 8 s ) were greater following 10 min of occlusion . In contrast to previous studies , this investigation has identified a greater brachial artery FMD in response to 10 versus 5 
    Output:
    
Application of this tool in a systematic review of FMD studies ( http://dx.doi.org/10.1016/j.atherosclerosis.2016.03.011 ) ( Greyling et al. , 2016 [ 1 ] ) indicated that adherence to expert consensus guidelines is strongly correlated to the reproducibility of FMD data