A Computer Simulation of Progesterone and Cox2 Inhibitor Treatment for Preterm Labor 英文参考文献.docVIP
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A Computer Simulation of Progesterone and Cox2 Inhibitor Treatment for Preterm Labor 英文参考文献
AComputerSimulationofProgesteroneandCox2
InhibitorTreatmentforPretermLabor
OzlemEquils1,2*,PriyaNambiar3,CalvinJ.Hobel4,RogerSmith5,CharlesF.Simmons1,2,ShireenVali3
1DepartmentofPediatrics,StevenSpielbergPediatricResearchCenter,BurnsandAllenResearchInstitute,Cedars-SinaiMedicalCenter,DavidGeffenSchoolofMedicine
atUniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,2MedicalDivision,PfizerInc.,NewYork,NewYork,UnitedStatesofAmerica,
3Cellworks Group Inc., Saratoga, California, United States of America, 4Obstetrics and Gynecology, Cedars-Sinai Medical Center, David Geffen School of Medicine at
UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,5EndocrineUnit,MothersandBabiesResearchCentre,JohnHunterHospital,Hunter
MedicalResearchInstitute,Newcastle,NewSouthWales,Australia
Abstract
Background:Sufficientinformationfrominvitroandinvivostudieshasbecomeavailabletopermitcomputermodelingof
theprocessesthatoccurinthemyometriumduringlabor.Thisdevelopmentallowstheinsilicoinvestigationofpathological
mechanismsandthetrialingofpotentialtreatments.
Methods/Results:Basedonthehumanliterature,wedevelopedacomputermodeloftheimmune-endocrineenvironment
ofthemyometrialcell.Theinteractionsbetweenmoleculesarerepresentedbydifferentialequations.Themodelisdesigned
to simulate the estrogen and progesterone receptor changes during pregnancy and particularly the changes in the
progesteronereceptor(PR)isoformsAandBthatarethoughttomediatefunctionalprogesteronewithdrawalinthehuman
atlabor.ParturitionisrepresentedbyanincreaseinthePRAtoPRBratiotolevelsseeninwomeninlabor.Infectionisshown
by inducing inflammation in the system by increasing phospho-IkB kinase concentration (IKK) levels; which lead to
increasedNF-kBactivation,causinganincreaseinthePRA/PRBratio.Weexaminedtheeffectsofprogesteroneorcyclo-
oxygenase2(Cox2)inhibitortreatmentsonthePRA/PRBratioinsilico.Themodelpredictedthathighdosesofprogesterone
andCox2inhibitionwouldbeeffectiveinpreventinganNF-
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