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简介：AIMEndothelin1(ET-1),apotentvasoconstrictorpeptide,isalsoregardedasanimportantetiologicalfactorinvolvedinmanycardiacdiseaseslikeheartfailureandcardiachypertrophy.Itmediatespathologicchangesbyformingan""""ETaxis""""attheupstreamtoionchannels,suchasstimulatingoxidantstress,elicitingcardiacremodelingbyproliferationofcardiomyocytes,inducingapoptosis,affectingsignaltransductionpathway,andmodulatingintranucleargenetranscription.ThepurposeofthisstudywastoinvestigatethepivotalrolebyETaxisinworseningarrhythmiasandcardiacfunctioninexperimentalhypertrophiccardiomyopathy(HCM)andheartfailure(HF)models.METHODSTheratHCMmodelwasinducedbys.cL-thyroxin(L-thy,0.2mg/Kg/d)for10d,

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简介：Gemfibrozilisawidelyusedlipidmodifyingdrugwithwell-establishedhypolipidemicandanti-atheroscleroticbenefits;however,thepresenceofacarboxylicacidmoietyinitsstructureisresponsibleforsideeffectsinthegastrointestinaltract.Theprincipleofbioisosterismwasappliedtodesignderivativesreplacingthecarboxylicacidgroup.Thecarboxylicacidgroupwasreplacedwithbioisotericgroups,suchas1,2,4-triazole-3-thiolandhydroxamicacid.Thederivativeswerethensynthesized,characterized,andevaluatedinratsforreducedgastrointestinalirritationandhypolipidemiceffects.Gemfibrozilwasusedasstandardforcomparison.Thederivativesdemonstratedlessgastricirritationandretainedhypolipidemiceffects,howeverthehypolipidemicaffectsweresignificantlylessthanthatofGemfibrozil.TheresultsofthisstudyoffersadirectionforfurtherresearchontheapplicationofbioisosterismforthedesignofnewderivativesofGemfibrozilandotherfibricacidderivatives.

简介：Thepresentresearcheffortwasaimedtodevelopcolontargeteddrugdeliverysystem(CTDDS)ofrhubarb,herbaldrugusingamixedfilmofpectinandethylcellulose(EC).Pectinandethylcelluloseweremixedinvariousproportionstocoatthecoretablettotargetcolon.Themethanolicextractofrhubarbwasusedandthedoseoftheextractineachformulationwasfinalizedbyestimatingtheemodincontentinitbyhighperformacethinlayerchromatography(HPTLC).Invitrodrugrelease,erosionstudyinpresenceandabsenceofpectinaseenzymeandreleaseconstant(K)ofzeroorderwasmeasuredforeachformulation.Theformulationwasoptimizedbyusing32fullfactorialdesign.Formulationhaving50%pectinasacoatingpolymerwith12%coatweightwasselectedasanoptimizedformulation(OF)onthebasisof%similaritywithmaximumdesirabilitybutthisformulationwasnotabletoretardthereleaseofdruginstomachandupperintestinefully.SoitwasfurthercoatedwithEudragitS100(ES)(3%coatweight).Theoptimizedformulation,coatedwithESindicatedsignificantlaxativeactivityonloperamideinducedconstipationinrats.TheresultsrevealedthatCTDDSofrhubarbusingtwocombinedapproachesofbiodegrablemicroflora-activatedsystemandpH-sensitivesystemexhibitedapromisingcolontargetingperformance.

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