title: Mechanism of Increased Intestinal Permeability in Acute Pancreatitis: Alteration in Tight Junction Proteins.
abstract: Intestinal permeability (IP) has been shown to be increased in acute pancreatitis (AP) and is considered to be responsible for development of septic complications. However, the mechanism of increase in IP is not well studied. We studied whether alteration in tight junction proteins (TJP) has any role in altered IP in patients with AP.
  
  
  
  This is a prospective study conducted at a tertiary care referral center. Twenty consecutive moderate and severe AP patients fulfilling the study criteria were included along with 20 controls that underwent gastroduodenoscopy for dyspepsia. IP was measured with lactulose mannitol (LM) ratio and TJP were studied by measuring expression of claudin-2 and claudin-4 in duodenal biopsy samples. Statistical analysis was done with STATA 13.0.
  
  
  
  IP as depicted by LM ratio was significantly higher in AP patients as compared with controls (4.659±10.4 vs. 0.101±0.297; P<0.001). Claudin-4 expression was reduced in duodenal biopsies in AP patients (P<0.001 for crypt intercellular junction and P=0.007 for crypt cytoplasm). However, LM ratio was not associated with either mortality (P=0.12) or development of infected pancreatic necrosis (P=0.3).
  
  
  
  IP is increased in AP. Alteration in TJP in the form of reduced claudin-4 expressions could be the possible mechanism for increased IP.
authors.affiliation: Departments of *Gastroenterology and Human Nutrition †Biostatistics ‡Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ujjwal
authors.initials: U
authors.lastname: Sonika
authors.forename: Pooja
authors.initials: P
authors.lastname: Goswami
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Thakur
authors.forename: Rajni
authors.initials: R
authors.lastname: Yadav
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Das
authors.forename: Vineet
authors.initials: V
authors.lastname: Ahuja
authors.forename: Anoop
authors.initials: A
authors.lastname: Saraya
mesh_terms: D000208:Acute Disease; D000328:Adult; D016022:Case-Control Studies; D062506:Claudin-4 / Q000378:metabolism*; D057167:Claudins / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007792:Lactulose / Q000652:urine; D008297:Male; D008353:Mannitol / Q000652:urine; D008875:Middle Aged; D010195:Pancreatitis / Q000150:complications / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D010539:Permeability; D010865:Pilot Projects; D011446:Prospective Studies; D012720:Severity of Illness Index; D062606:Tertiary Care Centers; D019108:Tight Junctions / Q000378:metabolism*; D055815:Young Adult
chemical_list: C491875:CLDN2 protein, human; C568157:CLDN4 protein, human; D062506:Claudin-4; D057167:Claudins; D008353:Mannitol; D007792:Lactulose