BASIC PHOTOMEDICINE.docx
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BASIC PHOTOMEDICINE.docx
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BASICPHOTOMEDICINE
BASICPHOTOMEDICINE
Ying-YingHuang1,PawelMroz2,andMichaelR.Hamblin1
1DepartmentofDermatology,HarvardMedicalSchool,BAR414,
WellmanCenterforPhotomedicine,MassachusettsGeneralHospital
40BlossomStreet,BostonMA02114
yhuang13@partners.org
hamblin@helix.mgh.harvard.edu
www2.massgeneral.org/wellman/people/mhamblin.asp
2DepartmentofPathology,FeinbergSchoolofMedicine
NorthwesternUniversity,Feinberg7-325
251E.HuronStreet,Chicago,IL60611
pawel-mroz@fsm.northwestern.edu
1.IntroductiontoPhotomedicine
Photomedicineincludesboththestudyandtreatmentofdiseasescausedbyexposuretolightandontheotherhandthediagnosticandtherapeuticapplicationsoflightfordetectingandcuringdisease.
Lightiscomposedofpacketsofenergycalledphotons(asdescribedintheIntroductoryPhotophysicsmodule).Forthepurposesofthissection,lightisdefinedasnon-ionizingelectromagneticradiationbetweenthewavelengthsof200nmtoabout10000nm.
Lightenergyiscapableofcausingheating,mechanicaleffectsandchemicalreactions.Thetransferoflightenergythroughphotonabsorptioncanleadtomanydifferentconsequencesinphotomedicine.Moreover,therearemanynewapproachesforusinglighttoseeinsidethebodytodetectanddiagnosedisease.
Someofthequestionsthatwillbediscussedinthissectionare:
* Whydoidenticalphotonsproduceharmfulmedicaleffectsinsomeinstances(suchasskincancer),buthelpfuleffectsinothers(suchasvitaminDproduction)?
* Isthereanywaytocontroltheeffectsofthelightenergyinphotomedicine?
* Whatlightsourcesarebeneficialinphotomedicine?
* Whatcanwedotomaximizethebeneficialeffects,whileminimizingthedeleteriouseffects?
2.DiseasesCausedbyLight
Humanshaveevolvedinanenvironmentwheretheyspendroughlyhalftheirlivesexposedtolightfromthesun.Theprecisecharacteristics(wavelengthdistributionandintensity)ofsunlightdependonwhichlatitudeontheearththeyinhabit,whatthetimeofdayis,andtheseasonoftheyear.Sunlightismoreintensethenearertotheequator,nearertomidday,andthenearertomidsummer.Inaddition,thedominantwavelengthsinsunlightareshorteratmidday,andlongerinmorningandevening.Thisisbecausethedistancethroughtheatmosphere,whichthesunlightmusttraveltoreachtheobserver,islongeratmorningandevening,becausethesunislowerinsky.Passingthroughtheatmosphereselectivelyabsorbsultravioletandbluewavelengths,leavingthered.
Becauseultraviolet(UV)lightisdamagingtotheskin,peoplewholivenearertotheequatortendtohavedarkerskinswithmoreoftheprotectivepigmentcalledmelanin.Partoftheproblemofskindiseasescausedbychronicsunexposurehasarisenbecausefairskinnedpeoplehavemigratedtocountriesnearertheequator,andanothercauseofdiseasesproducedbylightisduetothefashionforsunbathing.Figure1showsavarietyofskindiseasescausedorexacerbatedbysunexposure.
Figure1. Cutaneousdiseasescausedbylight.BCC,basalcellcarcinoma;PLE,polymorphiclighteruption.
Thetwodominantdiseasescausedbychronicsunexposurearephotoaging(leatherywrinkledskin),andtheinductionofskincancer(boththedangerousmalignantmelanomaandthelessdangerousnon-melanomaskincancer).Harmfulacuteeffectsofsunexposureincludesunburnandvariousphotodermatoses.TheinteractionofUVlightwiththeskincausesacomplicatedcascadeofeventsthatinvolvecellulardamageandrepair,pigmentationchanges,vascularandimmunesuppressioneffects.ItisstillunclearwhatarethehealthrisksintermsofincreasedratesofinfectionandcancerthatstemfromtheUV-inducedsuppressionoftheimmuneresponse.ResearchisongoingtodeterminethemolecularnatureofthecellulareventsandpathwaysthatleadtoUV-inducedsunburn,melanomaandnon-melanomaskincancer,andimmunesuppression(Ichihashietal.,2003).
UVBwavelengthsareabsorbedbythenucleicacidbasesthattendtohavepeaksat260nmbutthesepeaksarebroadandextendintothebiologicallyrelevant300-340nmregionreceivedbyskin.ThechemicalreactioncausedbytheUVabsorptionresultsintheformationofseveraltypesofDNAlesions,includingthymine-thyminedimers(Figure2).
Figure2. SchematicdepictionofUV-inducedDNAlesionformation(T-Tdimers).Theadjacentyellowthymineresiduesbecomelinkedtogether,andtheformationofthedimerdistortstheDNA,andthisdistortionisdetectedbytheDNArepairenzymes.
Withoutprotectionfromthesun'srays,justafewminutesofexposureeachdayovertheyearscancausenoticeablechangestotheskin.Freckles,agespots,spiderveinsontheface,roughandleatheryskin,finewrinklesthatdisappearwhenstretched,looseskin,ablotchycomplexion,actinickeratoses(thickwart-like,rough,reddishpatchesofskin),andskincancercanallbetracedtosunexposure."Photoaging"isthetermdermatologistsusetodescribethistypeofagingcausedbyexposuretothesun'srays.Theamountofphotoagingthatdevelopsdependson:
1)aperson'sskincolor,and2)theirhistoryoflong-termorintensesunexposure.
Peoplewithfairskinwhohaveahistoryofsunexposuredevelopmoresignsofphotoagingthanthosewithdarkskin.Inthedarkestskin,thesignsofphotoagingareusuallylimitedtofinewrinkles,andamottledcomplexion.Photoagingoccursoveraperiodofyears.Withrepeatedexposuretothesun,theskinlosestheabilitytorepairitself,andthedamageaccumulates.ScientificstudieshaveshownthatrepeatedUVexposurebreaksdowncollagenandimpairsthesynthesisofnewcollagen(Scharffetter-Kochaneketal.,1997).
Thesunalsoattacksourelastin.Sun-weakenedskinceasestospringbackmuchearlierthanskinprotectedfromUVrays.Skinalsobecomesloose,wrinkled,andleatherymuchearlierwithunprotectedexposuretosunlight.Thedeepwrinkles,agespots,andleatheryskinindicateprematureagingcausedbyyearsofunprotectedexposuretothesun.Peoplewholiveinsun-intenseareas,suchasFloridaorArizona,canshowsignsofphotoagingintheirtwenties,andcandevelopactinickeratoses(AK)andskincanceratayoungage.
Usingsunscreensandlimitingsunexposurearetwoapproachesformitigatingthechronicadverseeffectsofsunexposure.ThereisacounterbalancingbeneficialeffectofUVlightdeliveredtotheskinduringsunexposure.ThisistheincreaseinvitaminDbiosynthesisduetotheconversionofprovitaminD3(7-dehydrocholesterol)toprevitaminD3bytheactionofultravioletradiationontheskin(Holicketal.,1978).PrevitaminD3isthenthermallyconvertedtovitaminD3intheskin,andthevitaministhentransportedtotheliveronthevitaminD-bindingprotein.ItisthoughtthattheremightbeanunrealizedproblemofchronicvitaminDdeficiencyamongstpeoplewholiveinNorthernclimes,andthiscouldleadtoincreasedoccurrenceratesofsomecancers.Theexistenceoftwoopposinggoodandbadeffectsofsunexposurehasledonoccasiontoheateddebatesamongphotobiologistsanddermatologists.
Inaddition,thereexistanumberofrarerdiseasescharacterizedbyadverseeffects(eitheracute,chronicorboth)sufferedbyparticularindividualsexposedtodosesoflightthatwouldhavenoeffectonanormalpersonofsimilarskincolor.Manyofthesediseasesarecausedbysomegeneticmutationorabnormality,whereasotherareacquiredatvariousstagesoflife.Examplesofthesediseasesarexerodermapigmentosum,inwhichtheenzymesthatrepairDNAdamageintheskincausedbyUVlightarenotworkingproperly,leadingtoearlydevelopmentofskincancer;variousporphyriasinwhichdefectsinhemebiosynthesisleadtolevelsofphotosensitizingporphyrinsbeingpresentintheskin,andpolymorphiclighteruption(causeunknown)leadingtorashesonreceivingmildsunexposure.
Secondaryphotosensitivitydisordersinvolvephotosensitizingdrugs,suchassomeantibioticsandpsychoactivecompounds,photosensitizingingredientsinfoods(suchaslime,bergamot),andphotoallergicreactionsinwhichapersoncanbecomesensitizedtoanallergenthatisthenmuchworseaftersunexposure(Scheueretal.,2006).StJohnsWort(apopularherbalsupplementusedfordepressionthatcontainsthephotosensitizerhypericin)hasbeenresponsibleformanyofthesecasesofphotosensitivity(Kubinetal.,2005).
3.Photoprotection
InordertomitigatetheeffectsofUVdamagetotheskinreceivedfromthesun,modernpracticeistoencouragetheuseofsunscreens.Therearetwobasictypesoftopicalsunscreens:
* AbsorbersofUVradiation:
chemicalsunscreeningredientssuchaspara-aminobenzoicacid(PABA),cinnamates,salicylatesandbenzophenones(Dunfordetal.,1997).
* ReflectorsofUVradiation:
physicalsunscreeningredientssuchastitaniumorzincoxide.
Athirdclassoftopicalagentsistheantioxidants,suchasvitaminsEandC,whichdonotabsorborreflectUVradiation,butarebelievedtoenhancetheabilityofskincellstorepairdamageinducedbyUVradiation.
Sunscreensusuallyconsistofacombinationofseveralphotoprotectivechemicals.Thedegreeofprotectiontheyprovideismeasuredasasunprotectivefactor(SPF).Personswhoalwaysburnratherthantan;typicallyapersonwithpalewhiteskin,redorblondhair,andblueorgreeneyes-areathighestriskforphotoagingandskincancerandshouldalwaysusemaximumphotoprotection.Dermatologistsstronglyrecommendabroad-spectrumsunscreenwithSPFof15orhigherforallskintypes.SPFisdeterminedintheUnitedStatesbyaguidelineacceptedbys
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