Osvaldo Tiscornia

Influence of stress in acute pancreatitis and correlation with stress-induced gastric ulcer.

Background and Aims: In the general adaptation syndrome, gastric lesions are the first manifestation of stress. We hypothesized that acute pancreatitis (AP), an inflammatory acute disease, will be exacerbated if unchained following stress. Visceral hypersensitivity will be enhanced due to catecholaminergic discharges leading to an over-induction of the intrapancreatic cholinergic tone with increased response of the pancreocyte to cholecystokinin (CCK). Our aim was to investigate the influence of stress before AP on the later AP, and the effect of AP on underlying diseases such as gastric ulceration. Methods: The model of stress induced by restraint was followed by the bilio-pancreatic duct outlet exclusion closed duodenal loops model. The effect of autonomous arc reflex (AAR) interruption by anesthetics after stress but before AP was assessed. The participation of the vagal and sympathetic pathways and involvement of CCK-A receptors were considered. The degree of severity was evaluated using biochemical and histopathological analyses. Results: Induction of AP after stress was more severe than in its absence. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate foci were evenly distributed, being significantly greater in size and number after stress. Gastric ulceration evolved to ulcer, hemorrhage and gastric necrosis after AP triggering. Serum amylase, lipase, C-reactive protein, IL-6, IL-10 and plasmatic hsp72 as well as pancreatic and lung myeloperoxidase were significantly elevated in AP after stress while pancreatic amylase and lipase were significantly reduced. AAR blockage ameliorated AP after stress. Conclusions: Stress aggravates pancreatic pathology while AP deteriorates gastric pathology, and anesthetic treatment was beneficial for both. Restraint in other animal models can be useful to study the influence of stress in the evolution of other diseases.

The effect of chronic intraperitoneal infusion of bacterial endotoxin on exocrine pancreas function in rats.

SummaryConclusionThis study demonstrated that LPS infusion can induce tissue lesions and impair the exocrine protein secretion of the pancreas in rats.BackgroundThe effect of chronic ip infusion of lipopolysaccharide (LPS) on the exocrine pancreas function was studied in rats.MethodsFour milligrams per kilogram per day ofSalmonella typhi LPS were infused intraperitoneally by means of surgically implanted osmotic pumps. Rats were studied after 7-d LPS infusion.ResultsPlasma fibrinogen and amylase activity increased significantly in LPS-treated rats when compared with control rats. Histological examination of the pancreas showed congestion, infiltration, and focal necrosis in LPS-treated rats. The pancreas wet weight, as well as DNA and total soluble protein contents were significantly increased in LPS-treated animals when compared with controls. The pancreas protein output was significantly decreased in pure pancreatic juice, whereas the pancreatic juice flow rate was significantly increased in LPS-treated animals, when compared with controls. Electrophoretic patterns showed a marked decrease in digestive enzyme contents, whereas there was an increased content of 15 kDa protein.

Effects of sex and age on pancreatic secretion

SummaryThe secretory response of the exocrine pancreas to an intravenous bolus of secretin (1.0 U/kg) was studied in healthy men and women below and above 45 years of age. We studied the secretory pattern, i.e., electrolyte and enzyme secretion in 8 sequential, 10-min collections and cumulative values for each parameter. Within the male group, no significant changes were observed, except for higher amylase and lipase secretions in the older subjects. On the other hand, females over 45 yr old had secretory patterns that showed a decline of flow and of bicarbonate concentration and output. No significant secretory differences were observed in the groups of younger males and females. When the over-45 groups of men and women were compared, the women exhibited a significant decrease in bicarbonate concentration and output. Moreover, this group of women had a cumulative 80-min output of bicarbonate and lipase significantly below these parameters in the men. Possible mechanisms are discussed.

Experimental Model of Acute Pancreatitis in Wistar Rat: Glucocorticoid Treatment Profile

Severe acute pancreatitis may be triggered by an extrapancreatic insult at the peri-Vaterian duodenum such as that occurring in the short-term, 20 min closed duodenal loop model in Wistar rat, which mimics biliary acute pancreatitis or that following endoscopy. Glucocorticoids are immunological modulators whose therapeutic value is worth investigating. Wistar male rats were used under standardized conditions. Acute pancreatitis was induced by instillation of a 7% sodium tauraocholate solution with 5 drops of methylene blue to monitor absence of duodenal bilio pancreatic reflux into the peri-Vaterian duodenum for 20 min. Detection of biliopancreatic reflux with methylene blue was an exclusion criterion. Different doses and times of administration of subcutaneous hydrocortisone were evaluated. Biochemical assays were carried out in blood samples and pancreatic and lung tissue, while histpathological studies were done in the pancreas, lung liver, duodenum, spleen, kidneys, suprarenal glands, and stomach. Animals subjected to the experimental model developed severe acute pancreatitis. According to the dose and time ofadministration, hydrocortisone therapy was effective and beneficial at a dose of 4 mg/kg give 30 min before inducing acute pancreatitis. It was ineffective when doses were <4 mg/kg and given before sodium taurocholate harmful when the dose was >4 mg/kg and given either before or after. Thus, the proposed model is valid and useful to study the initiation mechanism of acute pancreatitis caused extrapancreatically while its amelioration by glucocorticoid is related the dose and time factor to achieve therapeutical results.

Acute Pancreatitis Possible Initial Triggering Mechanism and Prophylaxis

Background and Aims: Biliary acute pancreatitis or postendoscopic iatrogenia acute pancreatitis (AP) are likely triggered by autonomous arc reflexes (AAR) initiated in the peri-Vaterian duodenum (PV-D). The bilio-pancreatic duct outlet exclusion closed duodenal loops (BPDOE-CDL) model mimics these circumstances. Our aim was to validate this model and evaluate the role of AAR via their interruption with local anesthetics. Methods: Severe AP was induced in Wistar rats with the BPDOE-CDL model: extra-pancreatic insult was provoked in the PV-D by distension with 8% sodium taurocholate and methylene blue for 45 min to show the absence of duodenum pancreatic reflux. Treated experimental groups received a 2% lidocaine chlorhydrate gel instilled into the PV-D prior to triggering the AP, or before and after at the celiac-ganglia complex, or at both sites. The degree of severity was evaluated using biochemical and histopathological analysis. Results: Induction of AP by BPDOE- CDL was severe, with acinar and fat necrosis and hemorrhage with a greater foci number in the cephalic segment. Groups pretreated with local anesthetic developed mild or moderate AP characterized by edema and leukocyte infiltrate. Serum amylase, lipase and CRP were significantly reduced in all treated groups. Other blood metabolites and pancreatic myeloperoxidase, amylase and lipase, were significantly decreased. Conclusion: The BPDOE-CDL model was validated, emphasizing the importance of AAR as extrapancreatic initiators of AP. The interruption of AAR by lidocaine chlorhydrate prevented excessive pancreatic inflammation and diminished hemorrhage and necrosis and may prove a useful prophylactic procedure to prevent postendoscopic severe AP.

Physiopathogenic hypothesis of alcoholic pancreatitis: supranormal ecbolic stimulation of the «pancreon» units secondary to the loss of the negative component of pancreas innervation

In the rat, basal pancreatic secretion is generated and modulated by positive and negative duodeno-pancreatic reflexes. The former activates secretion, the latter acts as a “brake.” Impairment of this brake plays a crucial role in the pathogenesis of alcoholic pancreatitis by causing elevation of pancreatic cholinergic tone and inducing increased pancreon ecbolic response to CCK-PZ stimulation. Both factors lead to pancreatic damage by supranormal stimulation of the pancreon.

Colonic proteolysis following pancreatic duct ligation in the rat

SummaryLuminal proteolytic activity (PA) of different colonic segments was ascertained in animals subjected to pancreatic duct ligation (PDL) and in control rats. The PDL rats revealed a significant PA reduction in the cecum, proximal colon (P < 0.01), and distal colon (P < 0.05). Proteolytic activity, trypsin, and chymotrypsin activity in control rats diminished progressively from the cecum to the distal colon. Conversely in PDL rats, we found maximal PA in distal colon. The conclusion is drawn that a significant proportion of colonie proteolytic activity can be attributed to pancreatic proteases with a maximal contribution at cecum level.

Pure pancreatic juice in humans: orange-lemon-juice-induced secretory effects. comparative analysis with a regular meal, sorbitol, acidified peptone broth and secretin

SummaryThe secretory effect elicited by the ingestion of 100 ml of orange-lemon juice (O.-L.J.) was studied on pure pancreatic juice obtained from a catheter placed in the human Wirsung duct at surgery. These changes were compared with those evoked by a regular meal (R.M.), the ingestion of a Sorbitol solution (S.S.), the intragastric infusion of an acidified peptone broth (A.P.B.) and an i.v. single injection of secretin (Boots, 1.0 U/kg). The O.-L.J. induced purer pancreatic secretion response (flow, bicarbonate and enzyme output) than that triggered by the R.M., S.S. and A.P.B. The O.-L.J. evoked peak values, were observed earlier (60 min) than with a R.M. (90 min) ingestion. The 120-min-cumulative values confirmed these findings and disclosed that O.-L.J. elicits a rate of secretion and bicarbonate output closely similar to that of an i.v. secretin injection and amylase response greater than that evoked by this hormone. Thus, O.-L.J. ingestion proved to be an unexpected powerful stimulus of exocrine pancreatic secretion.

Influence of Hydrocortisone, Prednisolone, and NO Association on the Evolution of Acute Pancreatitis

Leukocyte activation, inflammatory up-regulation, and microcirculatory disruption associated with ischemia-reperfusion injury are hallmarks in the pathogenesis of acute pancreatitis (AP). NO donors ensure microvascular integrity, while glucocorticoids act as anti-inflammatory and immune modulator drugs. AP was induced by the biliopancreatic duct outlet exclusion-closed duodenal loops (BPDOE-CDLs) model. Treatment with hydrocortisone (6 mg/kg) or prednisolone (0.5 mg/kg) alone or together with DETA-NO (0.5 mg/kg) was done (a)1 hr pre or (b)1 hr post, or (c) 1 hr pre and 4 hr post ,or (d) 4 hr post triggering AP. NOS inhibition by l-NAME (15 mg/kg) and glucocorticoid receptor blockage by mifepristone (3 mg/kg) was considered. AP severity was assessed by biochemical and histopathological analyses. Treatment with glucocorticoids together with DETA-NO 1 hr pre and 4 hr post BPDOE-CDLs reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage, and neutrophil infiltrate were also decreased. Hydrocortisone together with DETA-NO rendered the best results. We conclude that AP severity was significantly diminished by glucocorticoids associated with DETA-NO, with the optimal dose and time point of administration being crucial to provide adequate protection against AP.

Ulex europeus agglutinin I binding pattern during chemical carcinogenesis in the rat gastrointestinal tract

Background. Fluorescein isothiocyanate–Ulex europeus agglutinin I stain (UEA1) was postulated as a prominent histochemical marker for premalignant mucosa in dimethylhydrazine (DMH)–treated animals. UEA1 (evaluated by two scanning methods) and high iron diamine Alcian blue (HIDAB) stain were used in attempt to detect premalignant colonic mucosa in this animal model. The authors also examined the influence of the duodenal medium on colonic segments transposed to the upper gastrointestinal tract.