trypsinogen and Pseudomonas-Infections

Pancreatic fistula after pancreatoduodenectomy (PD) is associated with high mortality and morbidity. Trypsinogen activation and bacteria, although hypothesized to be interrelated etiopathogenetically, have not had their relationship and pathogenic mechanisms elucidated. This study investigated bacterial involvement in pancreatic juice activation perioperatively after PD at sites of pancreatic fistula formation.. Fifty patients underwent PD; postoperative pancreatic fistulae were graded based on the International Study Group for Pancreatic Fistula grading criteria. Bacteria were isolated from cultures of drainage fluid. Digested peptides from trypsinogen and bacterial culture supernatants underwent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation and mass spectrometric analysis. Zymography was used to detect the trypsinogen activator.. Pseudomonas aeruginosa and Enterobacter cloacae isolated from drainage fluid in patients with grades B and C pancreatic fistulae could cause trypsinogen activation. Trypsinogen activation by P. aeruginosa and E. cloacae were preventable by the use of a serine protease inhibitor in vitro. A protease in the supernatant from P. aeruginosa-positive cultures acted as the trypsinogen activator.. Infection with P. aeruginosa perioperatively to PD entails secretion of a protease activator of trypsinogen to trypsin. Bacterial infection control in the perioperative PD period could be crucial to prevent development of pancreatic fistula.

Topics: Adult; Aged; Aged, 80 and over; Enzyme Activation; Female; Follow-Up Studies; Humans; Incidence; Japan; Male; Middle Aged; Pancreatic Fistula; Pancreaticoduodenectomy; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Surgical Wound Infection; Trypsinogen

An unavoidable outcome of cystic fibrosis newborn screening (CF NBS) programs is the detection of infants with an indeterminate diagnosis. The United States CF Foundation recently proposed the term cystic fibrosis transmembrane conductance regulator related metabolic syndrome (CRMS) to describe infants with elevated immunoreactive trypsinogen (IRT) on NBS who do not meet diagnostic criteria for CF. The objective of this study was to describe the clinical outcomes of infants with CRMS identified through an IRT/DNA algorithm. We reviewed the records of all infants with CRMS diagnosed at our CF Center from 2002 to 2010. We identified 12 infants, and compared them to 27 infants diagnosed with CF by NBS. Compared to CF patients, CRMS patients were more likely to be pancreatic sufficient as assessed by fecal elastase measurement (100% vs. 8%, P < 0.01). Their weight for age percentile was normal from birth. A positive oropharyngeal (OP) culture for Pseudomonas aeruginosa (Pa) was found in 25% of CRMS patients. One patient with the F508del/R117H/7T genotype was reassigned the diagnosis of CF after he had a positive OP culture for Pa, and his follow up sweat Cl at 1 year of life was 73 mmol/L. CF patients were more likely to receive oral antibiotics and be hospitalized for pulmonary symptoms. Our results indicate that CRMS patients can develop signs of CF disease, but have a milder clinical course than CF infants. Close initial monitoring of these patients is warranted. Pediatr. Pulmonol. 2011; 46:1079-1084. © 2011 Wiley Periodicals, Inc.

Topics: Anti-Bacterial Agents; Child, Preschool; Chlorides; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Feces; Female; Hospitalization; Humans; Infant; Infant, Newborn; Male; Metabolic Syndrome; Monitoring, Physiologic; Neonatal Screening; Oropharynx; Pancreatic Elastase; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Retrospective Studies; Sweat; Trypsinogen

Severe impairment of exocrine pancreatic secretion has recently been demonstrated in a clinical study in sepsis and septic shock patients. The purpose of this study was to further evaluate involvement of the pancreas in the acute phase reaction in sepsis. Using a normotensive rat model of Pseudomonas pneumonia-induced sepsis, we assessed the expression of PAP-I, amylase and trypsinogen mRNA, PAPI protein levels, and cytokine expression in the pancreas by Northern and Western blot analysis and RT-M PCR, respectively. Presence of several well-established features of pancreatitis in sepsis-induced animals were examined by biochemical and histopathological methods as well as by a determination of both water and myeloperoxidase content. Sepsis resulted in an up-regulation of PAP-I gene expression and increase in its protein level in pancreas while the mRNA levels of amylase and trypsinogen were down-regulated. Differences in the pancreatic cytokine expression, serum amylase and serum lipase levels, the occurrence of pancreatic edema as well as the severity of inflammatory infiltration and necrosis were not significantly different between sham and pneumonia groups. Acinar cells showed increased vacuolization in pneumonia animals 24 hours after the treatment. These findings demonstrate that the pancreas is actively involved in the acute phase reaction in sepsis of remote origin. This involvement occurs without concomitant biochemical and histopathologic alterations observed in pancreatitis. Taken all together, these features are indicative of a sepsis-specific dysfunction of the pancreas.

Topics: Acute-Phase Reaction; Amylases; Animals; Antigens, Neoplasm; Biomarkers, Tumor; Cytokines; Gene Expression Regulation; Lectins, C-Type; Leukocyte Count; Lipase; Male; Necrosis; Pancreas; Pancreatitis; Pancreatitis-Associated Proteins; Peroxidase; Pneumonia, Bacterial; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sepsis; Time Factors; Trypsinogen; Vacuoles