Natural disruption of group 2 phospholipase A2 gene protects against choline-deficient ethionine-supplemented diet-induced acute pancreatitis and lung injury.

OBJECTIVES: Group 2 phospholipase A2 (PLA2) plays an important role in the pathogenesis of multiple organ failure associated with acute pancreatitis. C57 BL/6J mice are natural group 2 PLA2 knockout mice lacking group 2 PLA2 mRNA. To clarify the role of group 2 PLA2 in the exacerbation of acute pancreatitis, we studied the biologic and histologic alterations in choline-deficient and ethionine-supplemented (CDE) diet-induced pancreatitis in group 2 PLA2-deficient C57 BL/6J mice and compared them with those in wild-type mice. METHODS: Female C57 BL/6J mice weighing 20 to 22 g were fed a CDE diet for 3 days to induce pancreatitis. Female C3H/HEJ mice were used as controls. Mice were killed on days 1, 2, and 3 after the onset of the CDE diet. The severity of pancreatitis was evaluated by survival rate, plasma PLA2 activity, serum amylase level, histologic changes in the pancreas and lung, and myeloperoxidase activity in the lung. RESULTS: The survival rate of C57 BL/6J mice was 100% up to day 3 after the onset of the CDE diet, whereas that of the control mice was 42% on day 3. Plasma PLA2 activity in control mice increased on day 3 but did not increase in C57 BL/6J mice. Serum amylase activity on day 3 in C57 BL/6J mice was 15,480 +/- 3036 SU/dL, which was significantly lower than that in the control mice (43,760 +/- 8657 SU/dL, P < 0.01). Histologic changes in the pancreas of C57 BL/6J mice were markedly milder than in control mice. The degree of alveolar membrane thickening and infiltration of inflammatory cells in the lung of C57 BL/6J mice were overtly less than those of the controls. Myeloperoxidase activity in the lung of C57 BL/6J mice was lower, albeit insignificant, than in C3H/HEJ mice. CONCLUSIONS: Natural disruption of the group 2 PLA2 gene protects against CDE diet-induced acute pancreatitis and associated lung injury. These findings support the view that group 2 PLA2 is one of the factors in the exacerbation of severe acute pancreatitis.

Increased expression of 19-kD interacting protein-3-like protein and the relationship to apoptosis in the lung of rats with severe acute pancreatitis.

OBJECTIVE: The aim of the present study was to determine the underlying cellular mechanisms in the pancreas after acute pancreatitis and to study the pathogenesis of pancreatitis-associated lung injury. We applied a differential display analysis to normal pancreas and to the pancreas with acute pancreatitis in rats, and we examined the expression of the identified gene in the lung as well as the pancreas after acute pancreatitis. DESIGN: Controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Ninety male Wistar rats. INVESTIGATIONS: Pancreatitis was induced by retrograde intraductal infusion of 4% sodium taurocholate (100 microL/100 g of body weight). Data were compared with data from controls (sham). MEASUREMENTS AND MAIN RESULTS: We cloned some expressed sequence tags and identified one complementary DNA fragment. The deduced protein was a polypeptide of 218 amino acids, which was almost identical to human 19-kD interacting protein-3-like (NIP3L) protein. The expression of rat NIP3L identified in this study increased slightly in the pancreas after induction of acute pancreatitis but showed a marked increase in the lung by both Northern and Western blot analysis. NIP3L immunoreactivity was noted in alveolar and epithelial cells of the control (sham) lung, and the immunoreactivity in these cells was elevated after induction of acute pancreatitis. Moreover, acute pancreatitis increased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive alveolar and bronchiolar cells in the lung. CONCLUSION: NIP3L may be involved in lung injury, which is one of the major causes of death in cases of severe acute pancreatitis.

Variable stiffness colonoscopes are associated with less pain during colonoscopy in unsedated patients.

OBJECTIVES: Application of a new variable stiffness colonoscope (VSC) is expected to control loop formation and to lessen patient discomfort. The aim of this prospective study was to compare the efficacy of VSC with a conventional colonoscope (CC) in unsedated colonoscopy, based on the experience of examiners. METHODS: Four-hundred sixty-seven patients were randomly assigned to undergo colonoscopy with either VSC or CC by an endoscopist, including experienced and less-experienced examiners. The percentages of completed procedure and time to cecal intubation were recorded. Patients were asked to rate pain on a 5-point pain score. RESULTS: The percentages of completed procedure with VSC and CC were 98% and 95%, respectively, by less-experienced hands, and 99% and 98%, respectively, by experienced hands. Time for cecal intubation with VSC and CC was 15.7 and 18.5 min, respectively, by less-experienced hands, and 9.8 and 10.6 min, respectively, by experienced hands. A significantly lower mean pain score was noted in VSC patients compared with CC patients, irrespective of experience of the examiner. The percent of patients rating the procedure as moderately or severely painful was significantly lower with VSC than with CC, both in less-experienced (19% vs 40%; p < 0.01) and experienced hands (15% vs 26%; p < 0.05). CONCLUSIONS: Our results indicated that VSC allows favorable examination compared with CC regarding completeness, time to cecal intubation, and comfort of patients undergoing unsedated colonoscopy, irrespective of the examiner's experience. These features suggest VSC as the preferred colonoscope for patients undergoing unsedated colonoscopy.

The elongated PAP II/Reg III mRNA is upregulated in rat pancreas during acute experimental pancreatitis.

INTRODUCTION: The pathogenesis and the mechanism of the development of severe acute pancreatitis are not clearly understood. AIMS: We performed differential display analysis to find genes that show transcriptional changes in the pancreas during the development of severe acute pancreatitis in the rat. METHODOLOGY: Twenty candidate pancreatitis-associated complementary DNA (cDNA) fragments were isolated. cDNA sequencing and subsequent database analysis revealed that one fragment (C18-2) among the 20 cDNA fragments showed no significant sequence similarity to previously reported genes, suggesting that it represented a novel gene. The rapid and high expression of C18-2 during the acute phase of pancreatitis suggested that the gene was involved in the development of acute pancreatitis. Therefore, we used rapid amplification of cDNA ends and identified the full-length cDNA. RESULTS: Analysis of the open reading frame of the cDNA indicated that the deduced protein from the messenger RNA (mRNA) was a polypeptide of 174 amino acids, unexpectedly similar to that of a known gene, rat pancreatitis-associated protein II/regenerating gene III (PAP II/Reg III). However, the length of the identified mRNA (1,467 base pairs) was longer than that of rat PAP II mRNA (885 base pairs), because the elongated mRNA was generated through the different polyadenylation site in the same gene. The elongated mRNA after acute pancreatitis was strongly induced in the restricted early phase, in comparison with the original mRNA. CONCLUSION: It is considered that the elongated mRNA affects the function of PAP II/Reg III protein because the elongated mRNA with long 3; untranslated regions is known to be involved in the translation efficiency. The identified mRNA may play an important role in the progression of pancreatitis.