2020
Hydrogel‐based 3D bioprints repair rat small intestine injuries and integrate into native intestinal tissue
Maina RM, Barahona MJ, Geibel P, Lysyy T, Finotti M, Isaji T, Wengerter B, Mentone S, Dardik A, Geibel JP. Hydrogel‐based 3D bioprints repair rat small intestine injuries and integrate into native intestinal tissue. Journal Of Tissue Engineering And Regenerative Medicine 2020, 15: 129-138. PMID: 33197151, DOI: 10.1002/term.3157.Peer-Reviewed Original ResearchConceptsIntestinal segmentsPost-operative day 7Male Sprague-Dawley ratsMale Wistar ratsSmall intestine injurySprague-Dawley ratsNative intestineBlinded histopathological analysisIntestinal failureStool outputNative intestinal tissueIntestine injuryIntraluminal perfusionRat vascular cellsHistopathological analysisIleocecal junctionWistar ratsIntestinal integrityIntestinal tissueDay 7Small intestineGenetic malformationsNormal activityWeight gainEnterotomyPenicillin G Induces H+, K+-ATPase via a Nitric Oxide-Dependent Mechanism in the Rat Colonic Crypt
Baratta VM, Norz V, Barahona MJ, Gisinger TM, Mulligan D, Geibel JP. Penicillin G Induces H+, K+-ATPase via a Nitric Oxide-Dependent Mechanism in the Rat Colonic Crypt. Cellular Physiology And Biochemistry 2020, 54: 1132-1142. PMID: 33175479, PMCID: PMC8095381, DOI: 10.33594/000000305.Peer-Reviewed Original ResearchConceptsRat colonic cryptsColonic cryptsNitric oxideNitric oxide-dependent mechanismPotassium homeostasisArginine methyl esterAmmonium prepulse techniqueIntracellular nitric oxideSodium-free conditionsL-NAMEDiarrheal statesATPase activityBACKGROUND/Presence of NOPenicillin G sodium saltAcute exposureL-arginineSmall intestineIsolated administrationN-nitroHomeostatic conditionsCryptsPrepulse techniqueSignificant reductionNovel mechanism
2019
The calcium‐sensing receptor: A novel target for treatment and prophylaxis of neratinib‐induced diarrhea
Lysyy T, Lalani AS, Olek EA, Diala I, Geibel JP. The calcium‐sensing receptor: A novel target for treatment and prophylaxis of neratinib‐induced diarrhea. Pharmacology Research & Perspectives 2019, 7: e00521. PMID: 31523434, PMCID: PMC6743423, DOI: 10.1002/prp2.521.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsCaSR activationCalcium-sensing receptorDose-dependent mannerFluid secretionRat intestineHER2-positive breast cancerKinase inhibitorsAdverse effectsChemotherapy-associated diarrheaNeratinib-induced diarrheaCommon side effectsIsolated intestinal segmentsPotent therapeutic targetIrreversible panPatients' qualityBreast cancerIntestinal segmentsSide effectsTherapeutic targetDiarrheaPronounced elevationIntraluminal calcium concentrationVivo modelNeratinibDesign and implementation of novel nutraceuticals and derivatives for treating intestinal disorders
Barahona MJ, Baratta V, Ollodart J, Mulligan D, Geibel JP. Design and implementation of novel nutraceuticals and derivatives for treating intestinal disorders. Future Medicinal Chemistry 2019, 11: 847-855. PMID: 30994367, PMCID: PMC8008207, DOI: 10.4155/fmc-2018-0313.Peer-Reviewed Original ResearchConceptsSignificant worldwide disease burdenSpectrum of illnessWorldwide disease burdenIntestinal fluid secretionSystemic side effectsCalcium-sensing receptorNovel therapeutic targetG protein-coupled receptorsSurgical therapyPharmaceutical optionsMucosal integrityDisease burdenIntestinal disordersNutraceutical therapyGastrointestinal diseasesGastrointestinal illnessSide effectsTherapeutic targetFluid secretionIntestinal cellsTherapyAdverse effectsNovel nutraceuticalsCaSRIllness
2018
Modulations in extracellular calcium lead to H+-ATPase-dependent acid secretion: a clarification of PPI failure
Kitay AM, Schneebacher MT, Schmitt A, Heschl K, Kopic S, Alfadda T, Alsaihati A, Link A, Geibel J. Modulations in extracellular calcium lead to H+-ATPase-dependent acid secretion: a clarification of PPI failure. AJP Gastrointestinal And Liver Physiology 2018, 315: g36-g42. PMID: 29517927, DOI: 10.1152/ajpgi.00132.2017.Peer-Reviewed Original ResearchConceptsAcid secretionParietal cellsExtracellular calciumGastric parietal cellsProton pump inhibitor exposureExtracellular CaPotassium-free conditionsRecurrent reflux symptomsCalcium sensing receptorGastric acid secretionPPI failurePPI therapyReflux symptomsIsolated gastric glandsInhibitor exposureCalcimimetic R568Pharmacological targetsSensing receptorAbsence of sodiumCalcium concentrationCaSRGastric glandsSecretionATPase activityExcretion pathway
2017
Activation of Secretagogue Independent Gastric Acid Secretion via Endothelial Nitric Oxide Synthase Stimulation in Rats
Kitay AM, Link A, Geibel JP. Activation of Secretagogue Independent Gastric Acid Secretion via Endothelial Nitric Oxide Synthase Stimulation in Rats. Cellular Physiology And Biochemistry 2017, 44: 1606-1615. PMID: 29212068, DOI: 10.1159/000485755.Peer-Reviewed Original ResearchConceptsNitric oxide synthaseGastric acid secretionAcid secretionL-arginineL-NAMENO/sGC/cGMP pathwayNitric oxideSGC/cGMP pathwayParietal cellsNitric oxide synthase stimulationSGC inhibitor ODQL-arginine exposureAcid-related diseasesPossible intracellular mechanismsNovel secretagogueRat parietal cellsIsolated gastric glandsUlcer diseaseOxide synthaseCGMP pathwayImmune functionImportant mediatorIntracellular mechanismsSecretionGastric glandsAcute Effects of Vitamin C Exposure On Colonic Crypts: Direct Modulation of pH Regulation
Aldajani MM, Vanicek CN, Alhazzaa N, Lysyy T, Agarwal R, Geibel JP. Acute Effects of Vitamin C Exposure On Colonic Crypts: Direct Modulation of pH Regulation. Cellular Physiology And Biochemistry 2017, 44: 377-387. PMID: 29132138, DOI: 10.1159/000484914.Peer-Reviewed Original ResearchConceptsVitamin CColonic cryptsAcute effectsDependent intracellular pH recoveryTumor formationIntracellular pH recoveryNew therapeutic agentsMM vitamin CColorectal cancerDistal colonLeading causeTranscellular passive diffusionBasolateral membraneAcute additionNormal colonic cryptsC exposureNutraceutical agentTherapeutic agentsPH recoveryIntracellular pH changesCancer cellsVitamin C.CryptsLow intracellularTight junctionsStomach and Bone
Kitay AM, Geibel JP. Stomach and Bone. Advances In Experimental Medicine And Biology 2017, 1033: 97-131. PMID: 29101653, DOI: 10.1007/978-3-319-66653-2_6.Peer-Reviewed Original ResearchConceptsBone metabolismGastric acid secretionCalcium-sensing receptorVitamin DParathyroid glandsAcid secretionGastrointestinal organsTherapeutic implicationsEndocrine modulatorsCalcium homeostasisDiseaseStomachOrgansMetabolismImportant playersIntermediary organDiverse tissuesDysfunctionCaSRPTHCalcitoninKidneySecretionIntestineReceptors
2016
Use of Fluorescein Isothiocyanate-Inulin as a Marker for Intestinal Ischemic Injury
AlKukhun A, Caturegli G, Munoz-Abraham AS, Judeeba S, Patron-Lozano R, Morotti R, Rodriguez-Davalos MI, Geibel JP. Use of Fluorescein Isothiocyanate-Inulin as a Marker for Intestinal Ischemic Injury. Journal Of The American College Of Surgeons 2016, 224: 1066-1073. PMID: 28017811, DOI: 10.1016/j.jamcollsurg.2016.12.016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFluorescein-5-isothiocyanateIntestinesInulinIschemiaMaleRatsRats, Sprague-DawleyConceptsFluorescein isothiocyanate-inulinIschemic injuryIntestinal ischemiaIntestinal transplantationFluid secretionIntestinal ischemic injuryIntestinal tissue samplesSmall intestine segmentsHEPES-Ringer solutionIntestinal graftMesenteric ischemiaIschemic intestineHistopathologic samplesExperimental armControl armControl intestineIschemic stateBlinded pathologistIschemiaIntestinal lumenIntestinal tissueIntestine segmentsScoring systemFluid shiftsInjurySecretagogue-dependent and -independent transport of zinc hydration forms in rat parietal cells
Ferstl FS, Kitay AM, Trattnig RM, Alsaihati A, Geibel JP. Secretagogue-dependent and -independent transport of zinc hydration forms in rat parietal cells. Pflügers Archiv - European Journal Of Physiology 2016, 468: 1877-1883. PMID: 27757581, DOI: 10.1007/s00424-016-1889-3.Peer-Reviewed Original ResearchConceptsGastroesophageal reflux diseaseAcid secretionParietal cellsSecretagogue-stimulated acid secretionRecurrence of symptomsAlternative treatment optionNumber of patientsNon-fasted conditionsApplication of bumetanideEffects of secretagoguesRat parietal cellsReflux diseaseInhibitor therapyTreatment optionsNon-fasted animalsLeading causeNeuronal activationNKCC1 transporterNeuronal pathwaysGastric acidInhibitor bumetanideSecretagogue carbacholFasted animalsMechanism of entryHormonal activation
2015
Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium
McNeer NA, Anandalingam K, Fields RJ, Caputo C, Kopic S, Gupta A, Quijano E, Polikoff L, Kong Y, Bahal R, Geibel JP, Glazer PM, Saltzman WM, Egan ME. Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium. Nature Communications 2015, 6: 6952. PMID: 25914116, PMCID: PMC4480796, DOI: 10.1038/ncomms7952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineChloridesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNA-Binding ProteinsGenetic TherapyHigh-Throughput Nucleotide SequencingHumansLactic AcidMice, Inbred C57BLNanoparticlesPeptide Nucleic AcidsPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerPolymersRespiratory MucosaConceptsFacile genome engineeringVivo gene deliveryBiodegradable polymer nanoparticlesTransient gene expressionNanoparticle systemsGene deliveryPolymer nanoparticlesGene correctionGenome engineeringNanoparticlesOff-target effectsPeptide nucleic acidLethal genetic disorderNucleic acidsDonor DNATarget effectsIntranasal deliveryDeliveryCystic fibrosisEngineeringOligonucleotideChloride effluxHuman cellsAirway epitheliumLung tissue
2014
Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1
Vucic E, Alfadda T, MacGregor GG, Dong K, Wang T, Geibel JP. Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1. Pflügers Archiv - European Journal Of Physiology 2014, 467: 1457-1468. PMID: 25127675, DOI: 10.1007/s00424-014-1593-0.Peer-Reviewed Original ResearchConceptsGastric parietal cellsPotassium channelsParietal cellsΒ-subunitKir1.1 channelsWild-type miceSecretagogue-stimulated gastric acid secretionApical poleGastric glandsLeak pathwayPotential therapeutic targetKir1.1Proton secretionRegulatory characteristicsKv7.1Therapeutic targetATPaseCell numberParietal cell numberCellsNormal gastric acid secretionSecretionInhibitorsAcid secretionMiceCalcium-sensing receptor 20 years later
Alfadda TI, Saleh AM, Houillier P, Geibel JP. Calcium-sensing receptor 20 years later. American Journal Of Physiology - Cell Physiology 2014, 307: c221-c231. PMID: 24871857, PMCID: PMC4121584, DOI: 10.1152/ajpcell.00139.2014.Peer-Reviewed Original ResearchConceptsCellular ion transport mechanismsG protein-coupled receptor familyProtein-coupled receptor familyEnvironmental cuesExtracellular environmentOrgan physiologyReceptor familySense changesDifferent tissuesCellular levelCalcium-sensing receptorIon transport mechanismsPhysiologyReceptor physiologyAmino acid concentrationsDisease statesReceptorsSystemic physiologyDiversity of locationsReceptor mutationsDifferent organ systemsImportant roleMembersFamilyHomologyA Novel Device to Preserve Intestinal Tissue Ex-Vivo by Cold Peristaltic Perfusion
Narayan RR, Pancer NE, Loeb BW, Oki K, Crouch A, Backus S, Chauhan Y, Patrón-Lozano R, Rodriguez-Davalos MI, Geibel JP, Fan RE, Zinter JP. A Novel Device to Preserve Intestinal Tissue Ex-Vivo by Cold Peristaltic Perfusion. Annual International Conference Of The IEEE Engineering In Medicine And Biology Society (EMBC) 2014, 2014: 3118-3121. PMID: 25570651, DOI: 10.1109/embc.2014.6944283.Peer-Reviewed Original Research
2013
Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR
Collaco AM, Geibel P, Lee BS, Geibel JP, Ameen NA. Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR. American Journal Of Physiology - Cell Physiology 2013, 305: c981-c996. PMID: 23986201, PMCID: PMC4109618, DOI: 10.1152/ajpcell.00067.2013.Peer-Reviewed Original ResearchConceptsV-ATPaseCystic fibrosis transmembrane conductance regulator (CFTR) channelV-ATPase complexV-ATPase functionBrush border membraneProton effluxRat Brunner's glandsIntestinal cellsCAMP/PKACaco-2BBe cellsBorder membraneApical domainCoimmunoprecipitation studiesCFTR distributionVacuolar ATPasesSubapical cytoplasmSpecific subunitsCAMP stimulationProton pumpCAMP treatmentEnterocyte brush border membraneSodium-hydrogen exchangerHydrogen exchangerApical membraneCFTRActivation of AMPK Inhibits Cholera Toxin Stimulated Chloride Secretion in Human and Murine Intestine
Rogers AC, Huetter L, Hoekstra N, Collins D, Collaco A, Baird AW, Winter DC, Ameen N, Geibel JP, Kopic S. Activation of AMPK Inhibits Cholera Toxin Stimulated Chloride Secretion in Human and Murine Intestine. PLOS ONE 2013, 8: e69050. PMID: 23935921, PMCID: PMC3728293, DOI: 10.1371/journal.pone.0069050.Peer-Reviewed Original ResearchConceptsIntestinal chloride secretionCholera toxinChloride secretionPharmacological activationFluid accumulationColonic cryptsSupplemental treatment strategyAcute diarrheal illnessChloride effluxCystic fibrosis transmembrane conductance regulatorExcised intestinal segmentsRat colonic cryptsMurine colonic mucosaMucosal sheetsDiarrheal illnessIntestinal loopsEnterotoxigenic diarrheaColonic mucosaTreatment strategiesIntestinal segmentsUssing chambersAMPK activator AICARMurine intestineTissue levelsMetforminEffect of NSAIDs on Na+/H+ exchanger activity in rat colonic crypts
Roginiel AC, Kohut DL, Kaur S, Saleh AM, Weber T, Geibel P, Singh H, Geibel JP. Effect of NSAIDs on Na+/H+ exchanger activity in rat colonic crypts. American Journal Of Physiology - Cell Physiology 2013, 305: c512-c518. PMID: 23739181, DOI: 10.1152/ajpcell.00303.2012.Peer-Reviewed Original ResearchConceptsRat colonic cryptsExchanger activityNonsteroidal anti-inflammatory drugsUpper GI injuryColonic cryptsLower GI bleedingUse of NSAIDsChronic inflammatory stateLower GI tractUse of suppositoriesEffects of NSAIDsAnti-inflammatory drugsGI injuryNSAIDs aspirinGI bleedingPain reliefRheumatoid diseaseEpithelial erosionsInflammatory stateMyocardial infarctionChronic conditionsMucosal barrierUlcer formationColonic tissueGastrointestinal tractIdentification of Functionally Distinct Na-HCO3 Co-Transporters in Colon
Barmeyer C, Ye JH, Soroka C, Geibel P, Hingsammer LM, Weitgasser L, Atway D, Geibel JP, Binder HJ, Rajendran VM. Identification of Functionally Distinct Na-HCO3 Co-Transporters in Colon. PLOS ONE 2013, 8: e62864. PMID: 23690961, PMCID: PMC3653958, DOI: 10.1371/journal.pone.0062864.Peer-Reviewed Original ResearchConceptsNa-HCO3 cotransportDistal colonProximal colonNBC activityNBC isoformsRat colonColonic epithelial cellsCrypt glandsSensitive transporterHCO3- secretionColonHCO3-dependent mechanismEpithelial cellsSaturable processHOE694Isoform 1Basolateral membraneCotransportPCR analysisNorthern blotDIDSMolecular studiesMolecular identityApparent KiCritical roleThe calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule
Capasso G, Geibel PJ, Damiano S, Jaeger P, Richards WG, Geibel JP. The calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule. Kidney International 2013, 84: 277-284. PMID: 23615500, DOI: 10.1038/ki.2013.137.Peer-Reviewed Original ResearchMeSH KeywordsAcid-Base EquilibriumAnimalsCalcimimetic AgentsCalciumHydrogen-Ion ConcentrationIn Vitro TechniquesKidney Tubules, ProximalMaleMiceMice, KnockoutNuclear ProteinsPerfusionPuncturesRatsRats, Sprague-DawleyReceptors, Calcium-SensingReceptors, G-Protein-CoupledSodium-Hydrogen ExchangersTranscription FactorsConceptsProximal tubulesLuminal calcium concentrationFluid reabsorptionAcid secretionKnockout miceCalcium ion concentrationCalcium concentrationRole of CaSRActivation of CaSRCalcium sensing receptorCalcium-sensing receptorMouse proximal tubulesProton secretionSodium-hydrogen exchangerCalcimimetic agentBicarbonate absorptionSensing receptorCaSRFluid absorptionSecretionReabsorptionMiceCalcimimeticsTubulesLuminal membraneActivation of the Ca2+-sensing receptor induces deposition of tight junction components to the epithelial cell plasma membrane
Jouret F, Wu J, Hull M, Rajendran V, Mayr B, Schöfl C, Geibel J, Caplan MJ. Activation of the Ca2+-sensing receptor induces deposition of tight junction components to the epithelial cell plasma membrane. Journal Of Cell Science 2013, 126: 5132-5142. PMID: 24013548, PMCID: PMC3828589, DOI: 10.1242/jcs.127555.Peer-Reviewed Original ResearchConceptsTJ assemblyMDCK cellsStable transfectionFunction mutant formZO-1Tight junction components ZO-1G protein-coupled receptorsHuman CaSRCell-cell contactEpithelial cell plasma membranesMadin-Darby canine kidney cellsCell plasma membraneStimulation of CaSRDivalent ion homeostasisCanine kidney cellsTight junctionsJunction-associated proteinsTight junction componentsEndogenous CaSRProtein kinasePlasma membraneIon homeostasisMutant formsChelator BAPTA-AMCell differentiation