Rubberprotector

Getoffthetreadmill

1.Thefailureofahigh-profilecholesteroldrughasthrownaspotlightonthecomplicatedmachinerythatregulatescholesterollevels.Butmanyresearchersremainconfidentthatdrugstoboostlevelsof'good'cholesterolarestilloneofthemostpromisingmeanstocombatspirallingheartdisease.

2.DrugcompanyPfizerannouncedon2Decemberthatitwascancellingallclinicaltrialsoftorcetrapib，adrugdesignedtoraiseheart-protectivehigh-densitylipoproteins(HDLs).Inatrialof15000patients，asafetyboardfoundthatmorepeoplediedorsufferedcardiovascularproblemsaftertakingthedrugplusacholesterol-loweringstatinthanthoseinacontrolgroupwhotookthestatinalone.

3.Thenewscameasakickintheteethtomanycardiologistsbecauseearliertestsinanimalsandpeoplesuggesteditwouldlowerratesofcardiovasculardisease."Therehavebeennoredflagstomyknowledge,"saysJohnChapman，aspecialistinlipoproteinsandatherosclerosisattheNationalInstituteforHealthandMedicalResearch(INSERM)inPariswhohasalsostudiedtorcetrapib."Thiscancellationcameasacompleteshock."

4.TorcetrapibisoneofthemostadvancedofanewbreedofdrugsdesignedtoraiselevelsofHDLs，whichferrycholesteroloutofartery-cloggingplaquestotheliverforremovalfromthebody.Specifically，torcetrapibblocksaproteincalledcholesterolestertransferprotein(CETP)，whichnormallytransfersthecholesterolfromhigh-densitylipoproteinstolowdensity，plaque-promotingones.Statins，incontrast，mainlyworkbyloweringthe'bad'low-densitylipoproteins.

Underpressure

5.Researchersarenowtryingtoworkoutwhyandhowthedrugbackfired，somethingthatwillnotbecomeclearuntiltheclinicaldetailsarereleasedbyPfizer.Onehintliesinevidencefromearliertrialsthatitslightlyraisesbloodpressureinsomepatients.Itwasthoughtthatthismildproblemwouldbeoffsetbytheheartbenefitsofthedrug.Butitispossiblethatitactuallyprovedfatalinsomepatientswhoalreadysufferedhighbloodpressure.Ifbloodpressureistheexplanation，itwouldactuallybegoodnewsfordrugdevelopersbecauseitsuggeststhattheproblemsarespecifictothiscompound.OtherprototypedrugsthatarebeingdevelopedtoblockCETPworkinaslightlydifferentwayandmightnotsufferthesamedownfall.

6.ButitisalsopossiblethatthewholeideaofblockingCETPisflawed，saysMotiKashyap，whodirectsatherosclerosisresearchattheVAMedicalCenterinLongBeach，California.WhenHDLsexcretecholesterolintheliver，theyactuallyrelyonLDLsforpartofthisprocess.SoinhibitingCETP，whichpreventsthetransferofcholesterolfromHDLtoLDL，mightactuallycauseanabnormalandirreversibleaccumulationofcholesterolinthebody."You'reblockingaphysiologicmechanismtoeliminatecholesterolandeffectivelyconstipatingthepathway,"saysKashyap.Goingup

7.Mostresearchersremainconfidentthatelevatinghighdensitylipoproteinslevelsbyonemeansoranotherisoneofthebestroutesforhelpingheartdiseasepatients.ButHDLsarecomplexandnotentirelyunderstood.Oneapproveddrug，calledniacin，isknowntobothraiseHDLandreducecardiovascularriskbutalsocausesanunpleasantsensationofheatandtingling.Researchersareexploringwhethertheycanbypassthissideeffectandwhetherniacincanlowerdiseaseriskmorethanstatinsalone.Scientistsarealsoworkingonseveralothermeanstobumpuphigh-densitylipoproteinsby，forexample，introducingsyntheticHDLs."Theonlythingweknowisdeadinthewateristorcetrapib，notthewholeideaofraisingHDL,"saysMichaelMiller，directorofpreventivecardiologyattheUniversityofMarylandMedicalCenter，Baltimore.

Questions7-13

Matchtorcetrapib，HDLs，statinandCETPwiththeirfunctions(Questions8-13)..WritethecorrectletterA，B，CorDinboxes8-13onyouranswersheet.NBYoumayuseanylettermorethanonce.

7.Ithasbeenadministeredtoover10,000subjectsinaclinicaltrial.

8.Itcouldhelpridhumanbodyofcholesterol.

9.Researchersareyettofindmoreaboutit.

10.Itwasusedtoreducethelevelofcholesterol.

11.AccordingtoKashyap，itmightleadtounwantedresultifit'sblocked.

12.Itproducedcontradictoryresultsindifferenttrials.

13.ItcouldinhibitLDLs.Listofchoices

A.TorcetrapicB.HDLSC.StatinD.CETP

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