2025
DSP-1, the major fibronectin type-II protein of donkey seminal plasma is a small heat-shock protein and exhibits chaperone-like activity against thermal and oxidative stress
Alim S, Cheppali S, Pawar S, Swamy M. DSP-1, the major fibronectin type-II protein of donkey seminal plasma is a small heat-shock protein and exhibits chaperone-like activity against thermal and oxidative stress. Biochimica Et Biophysica Acta (BBA) - Proteins And Proteomics 2025, 1873: 141064. PMID: 39956303, DOI: 10.1016/j.bbapap.2025.141064.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEquidaeFibronectinsHeat-Shock Proteins, SmallMaleMolecular ChaperonesOxidative StressPhosphorylcholineSemenConceptsChaperone-like activitySeminal plasmaFibronectin type IITetramer to monomersSperm capacitationSurface hydrophobicityMolecular chaperonesClient proteinsHeat shock proteinsBiophysical studiesAlcohol dehydrogenaseOxidative stressPhysiological ligandsShock proteinsProteinHead group moietySHspsBinding of phosphorylcholineCholine phospholipidsBindingFibronectinDehydrogenaseChaperoneSpermMammals
2021
Potency and Preclinical Evidence of Synergy of Oral Azole Drugs and Miltefosine in an Ex Vivo Model of Leishmania (Viannia) panamensis Infection
Fernández OL, Rosales-Chilama M, Quintero N, Travi BL, Wetzel DM, Gómez MA, Saravia NG. Potency and Preclinical Evidence of Synergy of Oral Azole Drugs and Miltefosine in an Ex Vivo Model of Leishmania (Viannia) panamensis Infection. Antimicrobial Agents And Chemotherapy 2021, 66: e01425-21. PMID: 34694879, PMCID: PMC8765415, DOI: 10.1128/aac.01425-21.Peer-Reviewed Original ResearchMeSH KeywordsAntiprotozoal AgentsAzolesHumansLeishmania guyanensisLeukocytes, MononuclearPhosphorylcholineConceptsFractional inhibitory concentration indexPeripheral blood mononuclear cellsL. panamensisHuman peripheral blood mononuclear cellsClinical strainsLeishmania panamensis infectionOral azole drugsOral combination therapyFailure of treatmentBlood mononuclear cellsEfficacy of treatmentNovel therapeutic strategiesEffectiveness of treatmentHigh potencyReduction of infectionEx vivo modelInhibitory concentration indexFree drug concentrationPanamensis infectionPreclinical evidenceCombination therapyMononuclear cellsAntimonial drugsCutaneous leishmaniasisDrug combinations
2020
Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma
Kaley TJ, Panageas KS, Pentsova EI, Mellinghoff IK, Nolan C, Gavrilovic I, DeAngelis LM, Abrey LE, Holland EC, Omuro A, Lacouture ME, Ludwig E, Lassman AB. Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma. Annals Of Clinical And Translational Neurology 2020, 7: 429-436. PMID: 32293798, PMCID: PMC7187704, DOI: 10.1002/acn3.51009.Peer-Reviewed Original ResearchConceptsRecurrent malignant gliomaDose-limiting toxicityMTOR inhibitor temsirolimusMalignant gliomasAkt inhibitor perifosinePhase I clinical trialDose level 3Dose level 7Phase II doseSynergistic anti-tumor effectKarnofsky performance statusPhase I trialDeadly primary brain cancerPI3K/Akt/mTOR axisPrimary brain cancerAkt/mTOR axisAnti-tumor effectsPotential therapeutic targetMost malignant gliomasPrior therapyTemsirolimus dosePerformance statusI trialIntracerebral hemorrhageCombined therapy
2018
Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions
Regli IB, Fernández OL, Martínez-Salazar B, Gómez MA, Saravia NG, Tacchini-Cottier F. Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions. Frontiers In Immunology 2018, 9: 3040. PMID: 30622537, PMCID: PMC6308327, DOI: 10.3389/fimmu.2018.03040.Peer-Reviewed Original ResearchConceptsNeutrophil effector functionsMeglumine antimoniateNeutrophil extracellular trapsEffector functionsLeishmania panamensisCell surface activation markersHuman neutrophilsExpression of CD66bReactive oxygen speciesSurface activation markersDrug-susceptible strainsOutcome of infectionMain causative agentChronic lesionsActivation markersDrug-resistant linesNeutrophil activationExtracellular trapsCutaneous leishmaniasisDrug susceptibilityNeutrophilsMurine neutrophilsDecreased expressionMiltefosineNET formationInterventions to treat cutaneous leishmaniasis in children: A systematic review
Uribe-Restrepo A, Cossio A, Desai MM, Dávalos D, del Mar Castro M. Interventions to treat cutaneous leishmaniasis in children: A systematic review. PLOS Neglected Tropical Diseases 2018, 12: e0006986. PMID: 30550538, PMCID: PMC6310290, DOI: 10.1371/journal.pntd.0006986.Peer-Reviewed Original ResearchMeSH KeywordsAntiprotozoal AgentsClinical Trials as TopicHumansLeishmaniaLeishmaniasis, CutaneousMeglumine AntimoniatePhosphorylcholineRifampinConceptsInternational Clinical Trials Registry PlatformAdverse eventsMeglumine antimoniateCutaneous leishmaniasisSystematic reviewClinical trialsManagement of CLClinical Trials Registry PlatformOld World cutaneous leishmaniasisTreatment of CLIntralesional meglumine antimoniateOld World CLEfficacy of cryotherapySerious adverse eventsTrials Registry PlatformHarms of interventionsRisk of biasEfficacy of treatmentFull-text reviewAmerican cutaneous leishmaniasisPROSPERO International registerRegistry PlatformCohort studySystemic therapyPediatric populationSimultaneous population pharmacokinetic modelling of plasma and intracellular PBMC miltefosine concentrations in New World cutaneous leishmaniasis and exploration of exposure–response relationships
Kip AE, del Mar Castro M, Gomez MA, Cossio A, Schellens JHM, Beijnen JH, Saravia NG, Dorlo TPC. Simultaneous population pharmacokinetic modelling of plasma and intracellular PBMC miltefosine concentrations in New World cutaneous leishmaniasis and exploration of exposure–response relationships. Journal Of Antimicrobial Chemotherapy 2018, 73: 2104-2111. PMID: 29757380, PMCID: PMC6251527, DOI: 10.1093/jac/dky143.Peer-Reviewed Original ResearchConceptsExposure-response relationshipProbability of curePopulation PK modelMiltefosine concentrationsDosing simulationsPK targetPK modelNew World cutaneous leishmaniasisPlasma concentration-time curveCutaneous leishmaniasis patientsPopulation pharmacokinetic modelLarge cohort studyPopulation pharmacokinetic modellingConcentration-time curvePlasma concentration ratioDistribution rate constantMiltefosine exposureCohort studyLeishmaniasis patientsPatient populationEffect compartmentCutaneous leishmaniasisDay 1Three-compartment modelPharmacokinetic modelling
2017
Cost-effectiveness of meglumine antimoniate versus miltefosine caregiver DOT for the treatment of pediatric cutaneous leishmaniasis
Berger BA, Cossio A, Saravia NG, del Mar Castro M, Prada S, Bartlett AH, Pho MT. Cost-effectiveness of meglumine antimoniate versus miltefosine caregiver DOT for the treatment of pediatric cutaneous leishmaniasis. PLOS Neglected Tropical Diseases 2017, 11: e0005459. PMID: 28384261, PMCID: PMC5404883, DOI: 10.1371/journal.pntd.0005459.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAntiprotozoal AgentsCaregiversChildChild, PreschoolCost-Benefit AnalysisDirectly Observed TherapyDrug CostsFemaleHumansInjections, IntramuscularLeishmaniaLeishmaniasis, CutaneousMaleMeglumineMeglumine AntimoniateMonte Carlo MethodOrganometallic CompoundsPhosphorylcholineSensitivity and SpecificityTreatment OutcomeUnited StatesConceptsPediatric cutaneous leishmaniasisMeglumine antimoniateCutaneous leishmaniasisGovernment payer perspectivePayer perspectivePatient's perspectiveMean differenceSocietal perspectiveCost-effectiveness analysisSurvey of providersOral miltefosineAdverse eventsObserved therapyPrimary outcomeHealthcare utilizationClinical trialsMean costTreatment efficacyDrug effectivenessMiltefosineHome caregiversSocietal costsLeishmaniasisCureTreatmentPharmacokinetics of Miltefosine in Children and Adults with Cutaneous Leishmaniasis
del Mar Castro M, Gomez MA, Kip AE, Cossio A, Ortiz E, Navas A, Dorlo TP, Saravia NG. Pharmacokinetics of Miltefosine in Children and Adults with Cutaneous Leishmaniasis. Antimicrobial Agents And Chemotherapy 2017, 61: 10.1128/aac.02198-16. PMID: 27956421, PMCID: PMC5328512, DOI: 10.1128/aac.02198-16.Peer-Reviewed Original ResearchConceptsCutaneous leishmaniasisMiltefosine concentrationsPeripheral blood mononuclear cellsInitiation of treatmentCompletion of treatmentBlood mononuclear cellsEnd of treatmentOutcome of treatmentConcentration-time curvePharmacokinetic clinical trialsClinical responsePediatric patientsPediatric populationMononuclear cellsTherapeutic regimensDrug exposureClinical trialsNoncompartmental analysisParasite eliminationTherapeutic outcomesStudy participantsMiltefosinePatientsLiquid chromatography-tandem mass spectrometryPK differences
2015
Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators
Gonzalez-Fajardo L, Fernández OL, McMahon-Pratt D, Saravia NG. Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators. PLOS Neglected Tropical Diseases 2015, 9: e0003820. PMID: 26024228, PMCID: PMC4449175, DOI: 10.1371/journal.pntd.0003820.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsOutcome of infectionIL-10Meglumine antimoniateIL-13Therapeutic strategiesAntileishmanial drugsTherapeutic responseCytokine secretionInfected peripheral blood mononuclear cellsParasite survivalHuman peripheral blood mononuclear cellsL. panamensis infectionsCutaneous leishmaniasis patientsPro-inflammatory cytokinesBlood mononuclear cellsIL-13 secretionIntracellular parasite survivalAssessment of hostViability of LeishmaniaEfficacy of treatmentPromising therapeutic strategySecretion of TNFInnovative therapeutic strategiesMonocyte-derived macrophages
2014
Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia
Fernández OL, Diaz-Toro Y, Ovalle C, Valderrama L, Muvdi S, Rodríguez I, Gomez MA, Saravia NG. Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia. PLOS Neglected Tropical Diseases 2014, 8: e2871. PMID: 24853871, PMCID: PMC4031164, DOI: 10.1371/journal.pntd.0002871.Peer-Reviewed Original ResearchConceptsV. panamensisLine treatmentClinical strainsDrug susceptibilitySecond-line treatmentFirst-line treatmentEmergence of resistancePopulations of LeishmaniaViannia speciesResistant clinical strainsAntimony susceptibilityClinical evidenceMeglumine antimoniatePentavalent antimonialsDermal leishmaniasisEpidemiologic differencesLeishmania VianniaProxy markerIntracellular amastigotesMunicipality of TumacoResistant strainsMiltefosineDisparate susceptibilityDrugsL. panamensis
2013
Treatment Failure and Miltefosine Susceptibility in Dermal Leishmaniasis Caused by Leishmania Subgenus Viannia Species
Obonaga R, Fernández O, Valderrama L, Rubiano L, del Mar Castro M, Barrera M, Gomez M, Saravia N. Treatment Failure and Miltefosine Susceptibility in Dermal Leishmaniasis Caused by Leishmania Subgenus Viannia Species. Antimicrobial Agents And Chemotherapy 2013, 58: 144-152. PMID: 24145529, PMCID: PMC3910710, DOI: 10.1128/aac.01023-13.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultATP Binding Cassette Transporter, Subfamily GATP-Binding Cassette TransportersChildDrug ResistanceFemaleHumansLeishmaniaLeishmaniasis, CutaneousMaleMiddle AgedMultidrug Resistance-Associated Protein 2Multidrug Resistance-Associated ProteinsPhosphorylcholineProspective StudiesTreatment FailureYoung AdultConceptsTreatment failureDermal leishmaniasisQuantitative reverse transcription PCRLoss of susceptibilityMiltefosine susceptibilityDrug susceptibilityIntracellular amastigotesL. panamensis infectionsL. braziliensis infectionPanamensis infectionMucocutaneous diseaseMiltefosine treatmentBraziliensis infectionCutaneous lesionsProspective evaluationMucosal diseaseDrug exposureReverse transcription-PCRClinical failureIndividual patientsGene polymorphismsLeishmania panamensisConcurrent conditionsDecreased expressionTransporter expression
2012
Novel Approach to In Vitro Drug Susceptibility Assessment of Clinical Strains of Leishmania spp
Fernández O, Diaz-Toro Y, Valderrama L, Ovalle C, Valderrama M, Castillo H, Perez M, Saravia NG. Novel Approach to In Vitro Drug Susceptibility Assessment of Clinical Strains of Leishmania spp. Journal Of Clinical Microbiology 2012, 50: 2207-2211. PMID: 22518860, PMCID: PMC3405580, DOI: 10.1128/jcm.00216-12.Peer-Reviewed Original ResearchConceptsClinical strainsMeglumine antimoniateDrug susceptibilityCell ratioParasite burdenAntileishmanial drugsDrug susceptibility assessmentReduction of infectionParasites/cellIntracellular burdenAntimonial drugsLeishmania panamensisDrug concentrationsEffective dosesHuman macrophagesPresence of drugsL. braziliensisParasite growthHost cell ratioMiltefosineLeishmania sppDrugsL. guyanensisLeishmaniaAntimoniateNoninferiority of Miltefosine Versus Meglumine Antimoniate for Cutaneous Leishmaniasis in Children
Rubiano L, Miranda M, Arenas S, Montero L, Rodríguez-Barraquer I, Garcerant D, Prager M, Osorio L, Rojas M, Pérez M, Nicholls R, Saravia N. Noninferiority of Miltefosine Versus Meglumine Antimoniate for Cutaneous Leishmaniasis in Children. The Journal Of Infectious Diseases 2012, 205: 684-692. PMID: 22238470, PMCID: PMC3266136, DOI: 10.1093/infdis/jir816.Peer-Reviewed Original ResearchConceptsPediatric cutaneous leishmaniasisMeglumine antimoniateCutaneous leishmaniasisTreatment failureInitiation of treatmentNoninferiority clinical trialPercent of childrenLow response rateOral miltefosineAdverse eventsMasked evaluationPrimary outcomeTreat analysisWeek 26Clinical trialsOral administrationAntimonial drugsTreatment groupsResponse rateAntimoniateLeishmania panamensisLeishmania guyanensisMiltefosineLeishmaniasisElimination rate
2011
Phosphoethanolamine methyltransferases in phosphocholine biosynthesis: functions and potential for antiparasite therapy
Bobenchik AM, Augagneur Y, Hao B, Hoch JC, Mamoun C. Phosphoethanolamine methyltransferases in phosphocholine biosynthesis: functions and potential for antiparasite therapy. FEMS Microbiology Reviews 2011, 35: 609-619. PMID: 21303393, PMCID: PMC4107886, DOI: 10.1111/j.1574-6976.2011.00267.x.Peer-Reviewed Original ResearchConceptsStress-resistant plantsImportant biochemical stepHuman malaria parasiteMethyl donor SAMPhosphocholine biosynthesisN-methyltransferasesFlorida lanceletDependent methyltransferasesNuclear divisionBiochemical stepsDependent methylationBiological functionsGene expressionGenetic characterizationDevelopment of therapiesMalaria parasitesMajor phospholipidsDiverse groupEnzymeSmall moleculesPlantsAntiparasite therapyEukaryotesPhosphoethanolamineMethyltransferasesHemolytic Phospholipase C Inhibition Protects Lung Function during Pseudomonas aeruginosa Infection
Wargo M, Gross M, Rajamani S, Allard J, Lundblad L, Allen G, Vasil M, Leclair L, Hogan D. Hemolytic Phospholipase C Inhibition Protects Lung Function during Pseudomonas aeruginosa Infection. American Journal Of Respiratory And Critical Care Medicine 2011, 184: 345-354. PMID: 21562128, PMCID: PMC3175536, DOI: 10.1164/rccm.201103-0374oc.Peer-Reviewed Original ResearchConceptsLung functionP. aeruginosa infectionAeruginosa infectionSignificant lung function impairmentLung function impairmentLung function declineBronchoalveolar lavage fluidPseudomonas aeruginosa infectionChronic lung infectionVirulence factorsP. aeruginosaP. aeruginosa virulence factorsPulmonary surfactant functionSingle virulence factorFunction declineMechanical ventilationFunction impairmentLavage fluidRespiratory endpointsSurfactant dysfunctionComputer-controlled ventilatorLung infectionAeruginosa virulence factorsStrain infectionLung physiology
2008
GbdR Regulates Pseudomonas aeruginosa plcH and pchP Transcription in Response to Choline Catabolites
Wargo M, Ho T, Gross M, Whittaker L, Hogan D. GbdR Regulates Pseudomonas aeruginosa plcH and pchP Transcription in Response to Choline Catabolites. Infection And Immunity 2008, 77: 1103-1111. PMID: 19103776, PMCID: PMC2643652, DOI: 10.1128/iai.01008-08.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAraC Transcription FactorBetaineCholineDNA Mutational AnalysisElectrophoretic Mobility Shift AssayGene Expression Regulation, BacterialMaleMiceMice, Inbred C57BLPhosphoric Monoester HydrolasesPhosphorylcholinePromoter Regions, GeneticPseudomonas aeruginosaPseudomonas InfectionsReverse Transcriptase Polymerase Chain ReactionSarcosineTranscription, GeneticTransferases (Other Substituted Phosphate Groups)ConceptsGlycine betainePlcH activityAraC family transcription factorElectrophoretic mobility shift assaysFamily transcription factorsEukaryotic cell membranesHemolytic phospholipase CMobility shift assaysP. aeruginosa virulenceProtein fusionsPromoter mappingTranscriptional activationTranscription factorsGbdRPhosphorylcholine phosphatasePromoter sequencesShift assaysGene expressionPromoter mutantsFeedback inductionMutantsTranscriptionPhospholipase CPrimary regulatorCell membrane
2007
Percutaneous Coronary Revascularization Using a Trilayer Metal Phosphorylcholine-Coated Zotarolimus-Eluting Stent
Abizaid A, Lansky AJ, Fitzgerald PJ, Tanajura LF, Feres F, Staico R, Mattos L, Abizaid A, Chaves A, Centemero M, Sousa AG, Sousa JE, Zaugg MJ, Schwartz LB. Percutaneous Coronary Revascularization Using a Trilayer Metal Phosphorylcholine-Coated Zotarolimus-Eluting Stent. The American Journal Of Cardiology 2007, 99: 1403-1408. PMID: 17493469, DOI: 10.1016/j.amjcard.2006.12.064.Peer-Reviewed Original ResearchMeSH KeywordsAgedAngioplasty, Balloon, CoronaryBlood Vessel Prosthesis ImplantationCardiovascular AgentsCoronary AngiographyCoronary CirculationCoronary RestenosisCoronary StenosisFemaleFollow-Up StudiesHumansMaleMiddle AgedPhosphorylcholineProspective StudiesProsthesis DesignResearch DesignSirolimusStentsTreatment OutcomeTunica IntimaUltrasonography, InterventionalConceptsCoronary artery stenosisQuantitative coronary angiographyZoMaxx stentCoronary angiographyArtery stenosisDe novo coronary artery stenosisSingle-arm prospective clinical trialDevice-deployment success ratesMajor adverse cardiac eventsSegment late lumen lossCoronary occlusive diseaseIntravascular ultrasound resultsNeointimal volume obstructionAdverse cardiac eventsIndependent core laboratoryLate lumen lossNative coronary arteriesPercutaneous coronary revascularizationProspective clinical trialsCoronary stent systemReduction of restenosisCoronary revascularizationVolume obstructionCardiac eventsObstructive lesions
1999
Detergents modulate dimerization, but not helicity, of the glycophorin A transmembrane domain 11Edited by G. von Heijne
Fisher L, Engelman D, Sturgis J. Detergents modulate dimerization, but not helicity, of the glycophorin A transmembrane domain 11Edited by G. von Heijne. Journal Of Molecular Biology 1999, 293: 639-651. PMID: 10543956, DOI: 10.1006/jmbi.1999.3126.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceButyratesCircular DichroismDetergentsDimerizationEnergy TransferFluorescent DyesGlycophorinsHumansKineticsMicellesMolecular Sequence DataPeptide FragmentsPhosphorylcholineProtein Structure, SecondaryQuaternary Ammonium CompoundsSodium Dodecyl SulfateSolventsSpectrometry, FluorescenceThermodynamicsConceptsSpecific chemical interactionsFörster resonance energy transferResonance energy transferSodium dodecyl sulfateComplex solventChemical interactionFar-UV circular dichroismCircular dichroismDodecyl sulfateTransmembrane helix associationDetergent micellesHelix associationEnergy transferThermodynamic measurementsHelix formationObserved KdZwitterionic detergentSecondary structureDimerizationG. von HeijneHelix dimerizationOrders of magnitudeDetergentsTransmembrane helicesTransmembrane domain
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