Science. Science. Cholesterol metabolism in the central nervous system during early development and in the mature animal.Neurology. Neurology. Neurology. Lancet. PNAS. Science. Neuroscientist. Isoform apoE associates more efficiently than apoE.Neurology. Review of epidemiological and preclinical studies.Review of human trials and recommendations.Microcirculation. Circulation. Hum. Mol. Genet. Disease Models Mechanisms Ox idative D N A damage has been implica teti in aging, carcinogenesis and other degenerative diseases.The urinary excre tion of the D N A repair product lydroxydeoxyguanosine has been as a noninvasive biomarker of oxidative D N A damage in hunrans invivo. This excretion corresponds ox idalive modifica tion of guanie bases per cell per day. Thus, lean andlor ma le subjects excreted mo re than obese and lor fema le sub jec ts, possibly related to differences innet abolicrate.Wesuggest that thei dividu al variationin the appa rentmassive extentoiox idati ve DN A dam age in hurnanspred ic ts the reasch Riboflavin rateoi ag ing and the riskoi canceraswell asotherdegene rative diseases.Duringmito chondria respiration a substant ialpart ofthecon sumed oxygen escapes thesimu ltaneous transferof foure lectrons and under goes stepw isesing lee lectron transfer, generat ing ROS, the supe rox ide an ion rad ical, hyd rogen pe rox ide, and thehyd roxylrad ical. Thefirstlineof defense against the supe rox ide rad icalis supe rox ide dismutase,whichforms hyd rogen pe rox ide. Th is mayin tu rn be reducedto wa terbyg lu ta th ione pe rox idaseor cata lase.Hydrogen pe roxide haslimited reactivity and crosses memb ranes easily.Inthe presence oftransit ion meta ls hyd rogen pe roxide is reducedtohydroxyl rad ica ls, the mostreactive ROS.Ionizingrad iation gener ates supe rox ide andhyd roxylrad ica ls. Thus, ROS maycause D N A proteinc ross links and sugar moiety damage aswell as specif icch emic almodific ationsofthepurine and pyrimidine bases. LYE juggesttl lattheindividu alt ti aiildgeillhumansp red ic tsthe degeneratrve diseases.The useol lN, jt ian la seol ie rs avalu abletool s. Th is mayin seor cata lase.These repairproductsare wa ter so lub le and readilyexc re tedinto theurinewithout furtherme tabo lism. A sixport valve direcls the effluent from tlie firstcol imri cmlto waste or on a cm cation exchange CE I co lumn monitored by ultraviolet de tectiol.The intra ind iv idualvari ation appearsto be somewhatless.S irpposed ly, thehighmitocliondri aloxy genmet aboli smin small an imals, such as roden ts, allowsgener ationof more ROS asthemostimport ant sou rceofoxid ative D N A damage. Urine wascollectedforhunderanesthes ia by meansof scrprapirbicbladdercathetersin pigs aged wk, forhby meansofbladderca theri zationin beag ledogaged mo and forhby meansofmetaboliccagesin male rats aged wk and rats aged wk. In te rspec ies corre lationof theexcretlorof hydroxyd oxyg anosine are showriwith anopensymboland smokers wtth aclo sedsymbol.The reason for these substantial inter laboratorydif fe renceswith respecttorodentda ta isunknownandinterl aboratory exchangeof samples has not been reported.However, they are less with respect to thym id ineglycolexcret ioninmice. The accumu lation may be a result of slight reduct ion of repair eff ic iency. Thevolatile phaseof tobaccosmo ke indu ceslipidperoxidation andlipoproteinoxidationin hum anp lasmainvitro. Intheplasmaof smokerslow con centrationsofthe importantantiox idan ts, ascorb ic acidand jcarotene, have been found, suggesting increased con sumption and redu ced antioxi dant capacity.