{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:14:54Z","timestamp":1785266094167,"version":"3.55.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Meconium ileus (MI) is a life-threatening obstruction of the intestines affecting \u223c15% of newborns with cystic fibrosis (CF). Current medical treatments for MI often fail, requiring surgical intervention. MI typically occurs in newborns with pancreatic insufficiency from CF. Meconium contains mucin glycoprotein, a potential substrate for pancreatic enzymes or mucolytics. Our study aim was to determine whether pancreatic enzymes in combination with mucolytic treatments dissolve obstructive meconium using the CF pig model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected meconium from CF pigs at birth and submerged it in solutions with and without pancreatic enzymes, including normal saline, 7% hypertonic saline, and the reducing agents N-acetylcysteine (NAC) and dithiothreitol (DTT). We digested meconium at 37 \u00b0C with agitation, and measured meconium pigment release by spectrophotometry and residual meconium solids by filtration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>In CF pigs, meconium appeared as a solid pigmented mass obstructing the ileum. Meconium microscopically contained mucus glycoprotein, cellular debris, and bile pigments. Meconium fragments released pigments with maximal absorption at 405\u2005nm after submersion in saline over approximately 8\u2005h. Pancreatic enzymes significantly increased pigment release and decreased residual meconium solids. DTT did not improve meconium digestion and the acidic reducing agent NAC worsened digestion. Pancreatic enzymes digested CF meconium best at neutral pH in isotonic saline. We conclude that pancreatic enzymes digest obstructive meconium from CF pigs, while hydrating or reducing agents alone were less effective. This work suggests a potential role for pancreatic enzymes in relieving obstruction due to MI in newborns with CF.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2024.1387171","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T04:57:11Z","timestamp":1712811431000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Pancreatic enzymes digest obstructive meconium from cystic fibrosis pig intestines"],"prefix":"10.3389","volume":"12","author":[{"given":"Gopinathan","family":"Gangadharan Nambiar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sussette","family":"Gonzalez Szachowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian F.","family":"Zirbes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared J.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda S.","family":"Powers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Meyerholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Thornell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Stoltz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S32","DOI":"10.1016\/j.jcf.2017.06.007","article-title":"Meconium ileus in cystic fibrosis","volume":"16","author":"Sathe","year":"2017","journal-title":"J Cyst Fibros"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1016\/j.jpedsurg.2018.05.016","article-title":"Predictors for surgical intervention and surgical outcomes in neonates with cystic fibrosis","volume":"53","author":"Jessula","year":"2018","journal-title":"J Pediatr Surg"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1053\/j.gastro.2006.07.016","article-title":"Relative contribution of genetic and nongenetic modifiers to intestinal obstruction in cystic fibrosis","volume":"131","author":"Blackman","year":"2006","journal-title":"Gastroenterology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1172\/JCI68867","article-title":"Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs","volume":"123","author":"Stoltz","year":"2013","journal-title":"J Clin Invest"},{"key":"B5","doi-asserted-by":"publisher","first-page":"eaau7531","DOI":"10.1126\/scitranslmed.aau7531","article-title":"In utero and postnatal VX-770 administration rescues multiorgan disease in a ferret model of cystic fibrosis","volume":"11","author":"Sun","year":"2019","journal-title":"Sci Transl Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.jcf.2022.04.005","article-title":"A case report of CFTR modulator administration via carrier mother to treat meconium ileus in a F508del homozygous fetus","volume":"21","author":"Szentpetery","year":"2022","journal-title":"J Cyst Fibros"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1016\/j.jpedsurg.2009.06.005","article-title":"Diminishing role of contrast enema in simple meconium ileus","volume":"44","author":"Copeland","year":"2009","journal-title":"J Pediatr Surg"},{"key":"B8","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1055\/s-2008-1071170","article-title":"Meconium ileus: a ten-year review of thirty-six patients","volume":"7","author":"Murshed","year":"1997","journal-title":"Eur J Pediatr Sur"},{"key":"B9","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.jpedsurg.2013.11.038","article-title":"Gastrointestinal surgery in cystic fibrosis: a 20-year review","volume":"49","author":"Farrelly","year":"2014","journal-title":"J Pediatr Surg"},{"key":"B10","first-page":"283","article-title":"Total parenteral nutrition in patients with short bowel syndrome","volume":"61","author":"Ekema","year":"2009","journal-title":"Minerva Pediatr"},{"key":"B11","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.idc.2017.05.007","article-title":"Prevention of central line-associated bloodstream infections","volume":"31","author":"Bell","year":"2017","journal-title":"Infect Dis Clin North Am"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1007\/s00383-007-2020-9","article-title":"Primary resection and anastomosis for complicated meconium ileus: a safe procedure?","volume":"23","author":"Jawaheer","year":"2007","journal-title":"Pediatr Surg Int"},{"key":"B13","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1007\/s00383-011-2906-4","article-title":"Issues in the management of simple and complex meconium ileus","volume":"27","author":"Karimi","year":"2011","journal-title":"Pediatr Surg Int"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1126\/science.1163600","article-title":"Dsisruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs","volume":"321","author":"Rogers","year":"2008","journal-title":"Science"},{"key":"B15","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1126\/scitranslmed.3001868","article-title":"The \u0394F508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs","volume":"3","author":"Ostedgaard","year":"2011","journal-title":"Sci Transl Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1186\/s13104-018-3855-y","article-title":"Glycogen depletion can increase the specificity of mucin detection in airway tissues","volume":"11","author":"Meyerholz","year":"2018","journal-title":"BMC Res Notes"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.2353\/ajpath.2010.090849","article-title":"Pathology of gastrointestinal organs in a porcine model of cystic fibrosis","volume":"176","author":"Meyerholz","year":"2010","journal-title":"Am J Pathol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"390","DOI":"10.5863\/1551-6776-24.5.390","article-title":"N-acetylcysteine for management of distal intestinal obstruction syndrome","volume":"24","author":"Schauble","year":"2019","journal-title":"J Pediatr Pharmacol Ther"},{"key":"B19","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1053\/jpsu.2002.32272","article-title":"New strategies in nonoperative management of meconium ileus","volume":"37","author":"Burke","year":"2002","journal-title":"J Pediatr Surg"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e124863","DOI":"10.1172\/jci.insight.124863","article-title":"Mucus strands from submucosal glands initiate mucociliary transport of large particles","volume":"4","author":"Fischer","year":"2019","journal-title":"JCI Insight"},{"key":"B21","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1097\/00000658-195703000-00017","article-title":"Management of meconium ileus; resection, Roux-en-Y anastomosis and ileostomy irrigation with pancreatic enzymes","volume":"145","author":"Bishop","year":"1957","journal-title":"Ann Surg"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e95332","DOI":"10.1172\/jci.insight.95332","article-title":"CF airway smooth muscle transcriptome reveals a role for PYK2","volume":"2","author":"Cook","year":"2017","journal-title":"JCI Insight"},{"key":"B23","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1164\/rccm.201508-1562OC","article-title":"Cystic fibrosis transmembrane conductance regulator in sarcoplasmic reticulum of airway smooth muscle. Implications for airway contractility","volume":"193","author":"Cook","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.ejphar.2015.06.051","article-title":"Hyper-osmolarity and calcium chelation: effects on cystic fibrosis mucus","volume":"764","author":"Ermund","year":"2015","journal-title":"Eur J Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/ng.2221","article-title":"Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis","volume":"44","author":"Sun","year":"2012","journal-title":"Nat Genet"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e81","DOI":"10.1038\/ctg.2017.10","article-title":"Impact of CFTR modulation on intestinal pH, motility, and clinical outcomes in patients with cystic fibrosis and the G551D mutation","volume":"8","author":"Gelfond","year":"2017","journal-title":"Clin Transl Gastroenterol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"G868","DOI":"10.1152\/ajpgi.00261.2017","article-title":"Linaclotide improves gastrointestinal transit in cystic fibrosis mice by inhibiting sodium\/hydrogen exchanger 3","volume":"315","author":"McHugh","year":"2018","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e91253","DOI":"10.1371\/journal.pone.0091253","article-title":"Characterization of defects in ion transport and tissue development in cystic fibrosis transmembrane conductance regulator (CFTR)-knockout rats","volume":"9","author":"Tuggle","year":"2014","journal-title":"PLoS One"},{"key":"B29","doi-asserted-by":"publisher","first-page":"S193","DOI":"10.1152\/physrev.1999.79.1.S193","article-title":"Pathophysiology of gene-targeted mouse models for cystic fibrosis","volume":"79","author":"Grubb","year":"1999","journal-title":"Physiol Rev"},{"key":"B30","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1159\/000091849","article-title":"Is the rat pancreas an appropriate model of the human pancreas?","volume":"6","author":"Case","year":"2006","journal-title":"Pancreatology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/S0022-3476(95)70153-2","article-title":"The consensus committee. Use of pancreatic enzyme supplements for patients with cystic fibrosis in the context of fibrosing colonopathy","volume":"127","author":"Borowitz","year":"1995","journal-title":"J Pediatr"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2024.1387171\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T04:57:14Z","timestamp":1712811434000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2024.1387171\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,11]]},"references-count":31,"alternative-id":["10.3389\/fped.2024.1387171"],"URL":"https:\/\/doi.org\/10.3389\/fped.2024.1387171","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,11]]},"article-number":"1387171"}}