?What Is CAM
اسلاید 1: www.tabaye.ir
اسلاید 2:
اسلاید 3: … medical and health care practices outside the realm of conventional medicine, which are yet to be validated using scientific methodsWhat Is CAM?Complementary: together with conventional practicesAlternative: in place of conventional practices
اسلاید 4: CAM DomainsBiologically Based SystemsManipulative and Body-Based SystemsMind-Body MedicineAlternative Medical SystemsEnergy TherapiesDiets HerbalsHomeopathy NaturopathyYoga Prayer MeditationMassage ChiropracticReiki Magnets Qi qongCommonCAMPractices
اسلاید 5: CAM’s Popularity: Growth of Visits to CAM Practitioners
اسلاید 6: Conventional Medicine “Push” FactorsFailure to yield curesAdverse effects of orthodox regimensLack of practitioner timeDissatisfaction with the technical approachFragmentation of care by specialists
اسلاید 7: CAM Therapies “Pull” FactorsMedia reports of dramatic resultsBelief that CAM treatments are naturalPatient empowerment Focus on spiritual and emotional well-beingTherapist providing “touch, talk, time”
اسلاید 8: CAM: The EvidenceEfficacyAbundant anecdotes and traditionSmall studiesSafetyDisplacing/interfering with proven therapiesInherent toxicity of CAM products
اسلاید 9: NCCAM’s MissionConduct rigorous research on CAM practices Educate and train CAM researchers Inform consumers and health professionals
اسلاید 10: Setting Priorities for NIH ResearchBurden of diseaseUse by U.S. publicOpportunity to reveal new principlesData from preliminary studies encouragingStudies are ethical, feasiblePrivate investment in research is low, lacking
اسلاید 11: Investment PrioritiesExtramural ProgramPhase I-III studies of many CAM approachesPre-clinical and translational researchResearch trainingIntramural ProgramClinical and translational studies of CAM approaches to age-related stressorsResearch training
اسلاید 12: NCCAM Research Support FY 2001ClinicalBasic
اسلاید 13: Status of Phase III Randomized Controlled TrialsSt. John’s Wort for major depressionIn pressShark cartilage for lung cancerIn progressGinkgo biloba to prevent dementiaIn progressAcupuncture for osteoarthritis painIn progress
اسلاید 14: Status of Phase III Randomized Controlled TrialsGlucosamine/chondroitin for osteoarthritisIn progressVitamin E/selenium for prostate cancerIn progressEDTA chelation therapy for CADAward pendingSaw palmetto/P. africanum for BPHAnnounced
اسلاید 15: CAM DomainsBiologically Based SystemsManipulative and Body-Based SystemsMind-Body MedicineAlternative Medical SystemsEnergy TherapiesDiets HerbalsHomeopathy NaturopathyYoga Prayer MeditationMassage ChiropracticReiki Magnets Qi qongCommonCAMPractices
اسلاید 16: St. John’s WortMedicinal herbWidely used $6 billion European sales (1998)$140 million U.S. sales (1998)Complex mixture of > 2 dozen compoundsAntidepressant constituent = hyperforinDrug interactionsoral contraceptivesindinavircyclosporin
اسلاید 17: ShraderPhillips LaakmannBjerkenWitteVolzSheltonWiedeyMontgomeryHolomanQuandtHoffmannHansgenSchilchSchmidtRehSommerHuberLehrlOsterheiKonig1996-2001 0 10 20 30 40Odds RatioBars = one standard deviation1996Systematic Review of SJW Studies
اسلاید 18: NIH Multicenter Trial of SJW in Major Depression8-week acute efficacy phase18-week maintenance phaseActive drug and placebo control arms
اسلاید 19: Study OutcomeChange in HAM-D scoreRate of complete response (CGI-I 2 and HAM-D 8)Primary Endpoints
اسلاید 20: It’s All “Natural”…!“People can be induced to swallow anything, provided it is sufficiently seasoned with praise.”Jean Moliere
اسلاید 21:
اسلاید 22: St. John’s Wort Lowers Blood Levels of HIV Protease Inhibitor IndinavirHIV Inhibition thresholdPiscitelli et al.
اسلاید 23: Botanical/Drug InteractionsGoalIncrease knowledge of botanicals and their interaction with other drugsCurrent UseEst. 18% of prescription drug users also use herbals, high-dose vitamin products, or both (1998)DesignsPre-clinical, Phase I and II trials
اسلاید 24: Chemoprotection: Defense Against ToxinsInhaledIngested• Xenobiotics = foreign chemicals• Endobiotics = chemicals produced by bodyAbsorbedSynthesizedLiverIntestinemonooxygenasesconjugation enzymestransporters
اسلاید 25: CYP3A Induction Causes Drug Interactions Expressed in liver and intestine Bind to CYP3A promoter Activated by xenobiotics and endobioticsCYP3ADrug A“Inducer”XRECYP3A?Drug B“Substrate”HO-Drug BexcretedIndinavirEthinylestradiolAtorvostatinCyclosporinWarfarinTamoxifenDoxorubicinRifampicinDexamethasoneTroglitazonePhenytoinTaxolSt. John’s Wort?Kliewer et al.
اسلاید 26: Nuclear Receptor SuperfamilyCARCOUP (a,b,g)DAXERR (a,b,g)FXRGCNF1HNF4 (a,g)LXR (a,b)NGFI-B (a,b,g)PNRPPAR (a,g,d)PXRrevErb (a,b) RXR (a,b,g)ROR (a,b,g)SF1 (a,b)SHPTlxTR2 (a,b)GlucocorticoidMineralocorticoidProgesteroneEstrogen (a,b)AndrogenThyroid Hormone (a,b)Vitamin Dall-trans Retinoic Acid (a,b,g)Classical ReceptorsOrphan ReceptorsCNDNALigand48 NRs in human genomeKliewer et al.
اسلاید 27: Human PXR Expression Patternheartbrainplacentalunglivermusclekidneypancreasspleenthymusprostatetestisovarysmall intestinecolonPBLNorthern blotKliewer et al.
اسلاید 28: PXR Binds to CYP3A PromoterCYP3ATGAACT caaagg AGGTCA<----- ----->CYP3A4 XRE- + ++ - +PXRRXRXREKliewer et al.
اسلاید 29: pseudohypericinamentoflavoneHypericinkaempferolluteolinmyricetinquercetinquercitrinisoquercitrinrutinhyperosidehyperforinumbelliferonescopoletinsitosterolSt. John’s Wort Activates PXRextract 1extract 2extract 3rifampicinSR12813Fold activation12345678hyperforinCell-basedreporter assayKliewer et al.
اسلاید 30: SJW Regulates Other PXR Target Genes Phase I enzymes (oxidation)CYP3A4CYP2B6CYP2A4ALDH1A4 Phase II enzymes (conjugation)SULT1A1 TransportersMDR1excretionsolubilization1 humanhepatocytesKliewer et al.
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