2023
Plasma renalase levels are associated with the development of acute pancreatitis
Wang M, Weiss F, Guo X, Kolodecik T, Bewersdorf J, Laine L, Lerch M, Desir G, Gorelick F. Plasma renalase levels are associated with the development of acute pancreatitis. Pancreatology 2023, 23: 158-162. PMID: 36697349, DOI: 10.1016/j.pan.2023.01.001.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsHumansMiceMonoamine OxidasePancreatitisPrognosisSeverity of Illness IndexConceptsAcute pancreatitisSevere diseasePlasma renalase levelsAcute pancreatitis patientsSevere acute pancreatitisAcute pancreatitis modelPlasma renalaseRenalase levelsSignificant morbidityPancreatitis patientsPlasma levelsHealthy controlsPancreatitis modelPancreatitisPatientsPlasma samplesRenalaseDiseaseNonparametric statistical analysisSecretory proteinsMorbidityStatistical analysisMortalityLevels
2021
Ovariectomy Affects Acute Pancreatitis in Mice
Wang M, Gorelick F. Ovariectomy Affects Acute Pancreatitis in Mice. Digestive Diseases And Sciences 2021, 67: 2971-2980. PMID: 34169436, PMCID: PMC8702581, DOI: 10.1007/s10620-021-07116-w.Peer-Reviewed Original ResearchConceptsOvariectomized mouse modelEffects of estradiolOvariectomized miceAcute pancreatitisEstradiol levelsPancreatitis severityMouse modelPancreatic studiesSevere acute injurySerum estradiol levelsMild acute pancreatitisAcute pancreatitis severityEstradiol conditionsHospital mortalityHourly injectionsAcute injuryOvariectomized modelFemale hormonesEstradiol injectionPancreatitisEstradiol depletionCausative roleDisease severityConclusionsThese findingsMice
2019
Animal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer.
Saloman JL, Albers KM, Cruz-Monserrate Z, Davis BM, Edderkaoui M, Eibl G, Epouhe AY, Gedeon JY, Gorelick FS, Grippo PJ, Groblewski GE, Husain SZ, Lai KKY, Pandol SJ, Uc A, Wen L, Whitcomb DC. Animal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer. Pancreas 2019, 48: 759-779. PMID: 31206467, PMCID: PMC6581211, DOI: 10.1097/mpa.0000000000001335.Peer-Reviewed Original ResearchRecent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders.
Gukovskaya AS, Gorelick FS, Groblewski GE, Mareninova OA, Lugea A, Antonucci L, Waldron RT, Habtezion A, Karin M, Pandol SJ, Gukovsky I. Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders. Pancreas 2019, 48: 459-470. PMID: 30973461, PMCID: PMC6461375, DOI: 10.1097/mpa.0000000000001298.Peer-Reviewed Original ResearchConceptsOrganelle dysfunctionCell death responseSecretion of proteinsAcinar cell homeostasisOrganelle disordersNascent proteinsDysfunctional organellesDeath responseAccessory proteinsVesicular compartmentsEndosomal pathwayCell homeostasisAcute pancreatitisEndoplasmic reticulumProtein synthesisCells triggersPancreatic acinar cellsLethal inflammatory diseaseDigestive enzymesCell constituentsRecent insightsDistinct mechanismsProteinOrganellesAcinar cell injury
2017
Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models
Biczo G, Vegh ET, Shalbueva N, Mareninova OA, Elperin J, Lotshaw E, Gretler S, Lugea A, Malla SR, Dawson D, Ruchala P, Whitelegge J, French SW, Wen L, Husain SZ, Gorelick FS, Hegyi P, Rakonczay Z, Gukovsky I, Gukovskaya AS. Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models. Gastroenterology 2017, 154: 689-703. PMID: 29074451, PMCID: PMC6369139, DOI: 10.1053/j.gastro.2017.10.012.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsArginineAutophagyBile Acids and SaltsCalcium SignalingCeruletideCholine DeficiencyCyclophilin DCyclophilinsDisease Models, AnimalEndoplasmic Reticulum StressEthionineGenetic Predisposition to DiseaseHumansLipid MetabolismMembrane Potential, MitochondrialMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial Proton-Translocating ATPasesPancreasPancreatitisPhenotypeRatsTime FactorsTrehaloseConceptsDevelopment of APAcute pancreatitisEndoplasmic reticulum stressLipid metabolismImpaired autophagyMitochondrial dysfunctionAnimal modelsL-arginine-induced pancreatitisTreatment of APCyclophilin D knockout micePathogenesis of APAdministration of trehalosePancreatic ER stressParameters of pancreatitisReticulum stressSevere acute pancreatitisPancreas of miceDifferent animal modelsER stressPrincipal downstream effectorPancreatic injuryPathologic responsePancreatitis tissuesCyclophilin DNormal pancreas
2015
Acute Pancreatitis—Progress and Challenges
Afghani E, Pandol SJ, Shimosegawa T, Sutton R, Wu BU, Vege SS, Gorelick F, Hirota M, Windsor J, Lo SK, Freeman ML, Lerch MM, Tsuji Y, Melmed GY, Wassef W, Mayerle J. Acute Pancreatitis—Progress and Challenges. Pancreas 2015, 44: 1195-1210. PMID: 26465949, PMCID: PMC4890478, DOI: 10.1097/mpa.0000000000000500.Peer-Reviewed Original ResearchAbdominal Paracentesis Drainage
Foglio EJ, Gorelick F. Abdominal Paracentesis Drainage. Journal Of Clinical Gastroenterology 2015, 49: 717-719. PMID: 26207360, DOI: 10.1097/mcg.0000000000000387.Peer-Reviewed Original Research
2013
Models of Acute and Chronic Pancreatitis
Lerch MM, Gorelick FS. Models of Acute and Chronic Pancreatitis. Gastroenterology 2013, 144: 1180-1193. PMID: 23622127, DOI: 10.1053/j.gastro.2012.12.043.Peer-Reviewed Original ResearchConceptsChronic pancreatitisModels of AcuteInfluence of inflammationAutoimmune chronic pancreatitisChronic ethanol feedingCombination of lipopolysaccharideMechanisms of pathogenesisAcinar cell responsesHuman diseasesPancreatic cancerSevere diseaseRodent modelsEthanol feedingSupraphysiologic concentrationsPancreatitisPancreatitis modelAnimal modelsTherapeutic interventionsCell responsesDiseaseFurther characterizationEarly stagesAcuteInflammationCholecystokinin
2012
Sterile Inflammatory Response in Acute Pancreatitis
Hoque R, Malik AF, Gorelick F, Mehal WZ. Sterile Inflammatory Response in Acute Pancreatitis. Pancreas 2012, 41: 353-357. PMID: 22415665, PMCID: PMC3306133, DOI: 10.1097/mpa.0b013e3182321500.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsHumansInflammationInflammation MediatorsPancreasPancreatitisSignal TransductionConceptsDamage-associated molecular patternsSterile inflammatory responseAcute pancreatitisInterleukin-1βInflammatory responseExperimental pancreatitisNOD-like receptor protein 3High mobility group box protein 1Toll-like receptor 4Remote organ injuryReceptor protein 3Acinar cellsExperimental acute pancreatitisIL-1 receptorNovel therapeutic targetBox protein 1Necrotic acinar cellsDAMP receptorsShock protein 70Disease resolutionPancreatic injuryOrgan injuryInitial injuryIL-18Pharmacologic antagonism
2011
TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis
Hoque R, Sohail M, Malik A, Sarwar S, Luo Y, Shah A, Barrat F, Flavell R, Gorelick F, Husain S, Mehal W. TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis. Gastroenterology 2011, 141: 358-369. PMID: 21439959, PMCID: PMC3129497, DOI: 10.1053/j.gastro.2011.03.041.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsAnti-Inflammatory AgentsApoptosisApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1CeruletideCytoskeletal ProteinsDisease Models, AnimalDNAInflammasomesInterleukin-1MacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNecrosisNeutrophil InfiltrationNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisPneumoniaProtein PrecursorsPurinergic P2X Receptor AntagonistsReceptors, Purinergic P2X7RNA, MessengerSeverity of Illness IndexSignal TransductionTaurolithocholic AcidToll-Like Receptor 9ConceptsToll-like receptor 9Acute pancreatitisWild-type miceAcinar cell deathPancreatic edemaTaurolithocholic acidDamage-associated molecular pattern receptorsResident immune cellsCell deathImmune cell populationsDevelopment of inflammationInitiation of inflammationCell populationsNew therapeutic strategiesMolecular pattern receptorsDAMP receptorsLung inflammationInflammatory infiltrateTLR9 expressionImmune cellsPancreatic necrosisReceptor 9TLR9 antagonistInflammasome activationPurinergic receptors
2007
Pancreatic protease-activated receptors: friend and foe
Gorelick F. Pancreatic protease-activated receptors: friend and foe. Gut 2007, 56: 901. PMID: 17566024, PMCID: PMC1994359, DOI: 10.1136/gut.2006.111245.Peer-Reviewed Original Research
2006
Vacuolar adenosine triphosphatase and pancreatic acinar cell function
Gorelick FS, Shugrue CA, Kolodecik TR, Thrower EC. Vacuolar adenosine triphosphatase and pancreatic acinar cell function. Journal Of Gastroenterology And Hepatology 2006, 21: s18-s21. PMID: 16958663, DOI: 10.1111/j.1440-1746.2006.04576.x.Peer-Reviewed Original Research
2003
Alcohol and Zymogen Activation in the Pancreatic Acinar Cell
Gorelick FS. Alcohol and Zymogen Activation in the Pancreatic Acinar Cell. Pancreas 2003, 27: 305-310. PMID: 14576492, DOI: 10.1097/00006676-200311000-00006.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsSupraphysiologic concentrationsAcute pancreatitisAbility of alcoholMechanism of sensitizationEarly featureIsolated aciniCholecystokininPancreatic aciniInduced activationSensitizationPancreatitisAciniZymogen activationActivationLysosomal markersGranule compartmentCellsActivation of zymogens
2002
Alcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells
Lu Z, Karne S, Kolodecik T, Gorelick FS. Alcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells. AJP Gastrointestinal And Liver Physiology 2002, 282: g501-g507. PMID: 11842000, PMCID: PMC2830557, DOI: 10.1152/ajpgi.00388.2001.Peer-Reviewed Original Research
1999
ETIOPATHOGENESIS OF ACUTE PANCREATITIS
Karne S, Gorelick F. ETIOPATHOGENESIS OF ACUTE PANCREATITIS. Surgical Clinics Of North America 1999, 79: 699-710. PMID: 10470320, DOI: 10.1016/s0039-6109(05)70036-0.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAlcohol DrinkingAnimalsCholelithiasisCytokinesEnzyme PrecursorsHumansPancreatitisConceptsAcute pancreatitisCourse of APPotent proteolytic enzymesCapillary leak syndromeAcinar cellsPreliminary clinical studySpecific clinical settingsSystemic complicationsLeak syndromeCytokine inhibitorsInflammatory moleculesCascade of eventsInflammatory cellsPancreatic edemaVasoactive moleculesClinical studiesParticular neutrophilsPancreatitisFurther secretionClinical settingNitric oxideComplement systemCytokinesPremature activationImmediate releaseMechanisms of intracellular zymogen activation
Gorelick F, Otani T. Mechanisms of intracellular zymogen activation. Best Practice & Research Clinical Gastroenterology 1999, 13: 227-240. PMID: 11030603, DOI: 10.1053/bega.1999.0021.Peer-Reviewed Original ResearchConceptsTrypsinogen activation peptideAcinar cellsZymogen processingDistinct subcellular compartmentsZymogen activationSerine proteasesIntracellular serine proteaseIntracellular zymogen activationCaerulein-induced pancreatitisAcinar cell compartmentPancreatic acinar cellsAcute pancreatitisSubcellular compartmentsHuman pancreatitisPancreatitisExperimental pancreatitisSupramaximal concentrationsHereditary pancreatitisLow-pH compartmentsPancreatic aciniTrypsinogen activationTrypsinogen processingGenetic diseasesCell pathwaysIntracellular activation
1998
Codistribution of TAP and the granule membrane protein GRAMP-92 in rat caerulein-induced pancreatitis
Otani T, Chepilko S, Grendell J, Gorelick F. Codistribution of TAP and the granule membrane protein GRAMP-92 in rat caerulein-induced pancreatitis. American Journal Of Physiology 1998, 275: g999-g1009. PMID: 9815030, DOI: 10.1152/ajpgi.1998.275.5.g999.Peer-Reviewed Original ResearchConceptsAcinar cell compartmentNumber of vesiclesRecycling endosomesSupranuclear compartmentPancreatic acinar cellsTime-dependent mannerProcessing siteCell compartmentTrypsinogen processingPhysiological levelsZymogen granulesImmunofluorescence studiesCaerulein-induced pancreatitisAcinar cellsActivation peptideTrypsinogen activation peptidePathological activationCompartmentsActivation
1995
Lysosomal enzymes and pancreatitis
Gorelick F, Matovcik L. Lysosomal enzymes and pancreatitis. Gastroenterology 1995, 109: 620-625. PMID: 7615215, DOI: 10.1016/0016-5085(95)90355-0.Peer-Reviewed Original Research
1994
Effect of buprenorphine on pancreatic enzyme synthesis and secretion in normal rats and rats with acute edematous pancreatitis
Ogden JM, Modlin IM, Gorelick FS, Marks IN. Effect of buprenorphine on pancreatic enzyme synthesis and secretion in normal rats and rats with acute edematous pancreatitis. Digestive Diseases And Sciences 1994, 39: 2407-2415. PMID: 7525167, DOI: 10.1007/bf02087658.Peer-Reviewed Original ResearchConceptsAcute pancreatitisPancreatic enzyme secretionPancreatic enzyme synthesisAmylase secretionAmylase contentDevelopment of APEnzyme secretionSevere acute pancreatitisEffects of buprenorphineEffects of opiatesExperimental acute pancreatitisAcute edematous pancreatitisGroups of ratsSite of administrationNegative feedback inhibitionPancreatic edemaPancreatic stimulantsEdematous pancreatitisNormal ratsPancreatic massPancreatic secretionPancreatitisGroup IIControl groupGroup I
1993
Influence of Chloroquine on Diet-Induced Pancreatitis
Leach S, Bilchik A, Karapetian O, Gorelick F, Modlin I. Influence of Chloroquine on Diet-Induced Pancreatitis. Pancreas 1993, 8: 64-69. PMID: 7678327, DOI: 10.1097/00006676-199301000-00013.Peer-Reviewed Original ResearchConceptsHigh-dose chloroquineAcidic subcellular compartmentsDiet-induced pancreatitisEthionine-supplemented dietRegular laboratory chowYoung female miceInfluence of chloroquineIntracellular zymogen activationCDE dietAcute pancreatitisContinuous infusionFemale miceLaboratory chowControl animalsPancreatitisExperimental pancreatitisAdditional potential effectsLow-pH compartmentsTrypsinogen contentPancreatic aciniChloroquineAcinar cellsTryptic activityAnimalsDigestive zymogens