Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems. Acute fluid collections and pseudocyst formation are the most frequent complications of acute pancreatitis.

The aims of this study were to evaluate the incidence, risk factors, and clinical course of pancreatic fluid collections and pseudocyst formation following acute pancreatitis.

A prospective multicenter study was conducted in five participating centers with 302 patients diagnosed with acute pancreatitis from January 2011 to July 2012.

The incidence of pancreatic fluid collections and pseudocyst was 42.7 and 6.3 %, respectively. Patients with fluid collections were significantly younger, compared to those without fluid collections (51.5 ± 15.9 vs. 60.4 ± 16.5 years, P = 0.000). The proportion of alcoholic etiology (54.3 %) in patients with fluid collections was significantly higher compared to other etiologies (P = 0.000). C-reactive protein (CRP) (48 h) was significantly higher in patients with fluid collections, compared to patients without fluid collections (39.2 ± 77.4 vs. 15.1 ± 36.2 mg/dL, P = 0.016). LDH (48 h) was significantly higher in patients with pseudocyst formation, compared to patients with complete resolution (1,317.6 ± 706.4 vs. 478.7 ± 190.5 IU/L, P = 0.000). Pancreatic fluid collections showed spontaneous resolution in 69.8 % (90/129) and 84.2 % of the pseudocysts disappeared or decreased in size during follow up.

Age, CRP (48 h), and alcohol etiology are risk factors for pancreatic fluid collections. LDH (48 h) appears to be a risk factor for pseudocyst formation. Most pseudocysts showed a decrease in size or spontaneous resolution with conservative management.

The aim of this study was to analyze the incidence, risk factors, and clinical outcomes of pancreatic pseudocyst after acute or acute-on-chronic pancreatitis.

We retrospectively reviewed the medical records of 350 patients with acute pancreatitis and 55 patients with acute-on-chronic pancreatitis.

Pancreatic pseudocyst developed in 14.6% of acute pancreatitis and in 41.8% of acute-on-chronic pancreatitis (P = 0.00). In the acute-on-chronic pancreatitis group, interval from symptom onset to hospital visit was longer, and the incidence of recurrent pancreatitis and alcoholic etiology was higher than that of the acute pancreatitis group (P < 0.01). There was no significant difference in the spontaneous resolution rate between both groups. Of the total 68 conservatively treated patients with pseudocyst, the pseudocyst decreased in size or disappeared in 77.9% and showed no change in 1.5%. The risk factors of pseudocyst were the presence of underlying chronic pancreatitis, the interval from symptom onset to visiting the hospital, and an alcoholic etiology. The factor-predicted spontaneous resolution was a single lesion.

Pseudocyst developed more frequently in patients with acute-on-chronic pancreatitis, and most pseudocysts improved spontaneously irrespective of underlying chronic pancreatitis. A longer period of a "wait-and-see" policy for more than 6 weeks is suggested for asymptomatic pseudocyst, especially for a single lesion.

Epithelial cells have distinct apical and basolateral plasma membrane domains separated by tight junctions. This phenotype is essential for the directional transport functions of epithelial cells. Here we characterized a well-differentiated pancreatic epithelial cell line to establish a useful model for understanding the mechanisms involved in the regulation of junctional complexes, polarity, and disease processes in the pancreas.

Immunofluorescence of cell junction marker proteins and electron microscopy were used to determine the presence of tight junctions, adherens junctions, and desmosomes. The functionality of tight junctions was tested by transepithelial resistance measurements and transepithelial permeability studies of nonionic molecules. Tight junction function in polarity was determined by laser scanning confocal microscopy.

Immunofluorescence analysis in HPAF-II cells revealed tight junction localization of ZO-1, occludin, and claudin-4; adherens junction localization of E-cadherin and beta-catenin; and desmosomal localization of desmocollin. Transmission electron microscopy showed the presence of tight junctions, adherens junctions, and des-mosomes, and freeze-fracture electron microscopy revealed the presence of distinct anastomosing tight junction strands. Transepithelial electrical resistance and permeability measurements revealed functional tight junctions. In addition, 3-dimensional images of the monolayer generated by laser scanning confocal microscopy revealed that HPAF-II cells show polarity. Immunoblotting and RT-PCR analyses revealed high expression levels of E-cadherin and Na,K-ATPase beta-subunit but low levels of the transcription factor Snail in HPAF-II cells compared with MiaPaCa-2 cells.

The HPAF-II cell line is a well-differentiated human pancreatic carcinoma cell line that should be useful as a model for studies aimed at understanding epithelial polarity, regulation of junctional complexes, and disease processes in pancreas.

Acute pancreatitis is a disorder that has numerous causes and an obscure pathogenesis. Bile duct stones and alcohol abuse together account for about 80% of acute pancreatitis. Most episodes of biliary pancreatitis are associated with transient impaction of the stone in the ampulla (that causes obstruction of the pancreatic duct, with ductal hypertension) or passage of the stone though and into the duodenum. Other causes of acute pancreatitis are various toxins, drugs, other obstructive causes (such as malignancy or fibrotic sphincter of Oddi), metabolic abnormalities, trauma, ischemia, infection, autoimmune diseases, etc. In 10% of cases of acute pancreatitis, no underlying cause can be identified; this is idiopathic pancreatitis. Occult biliary microlithiasis may be the cause of two thirds of the cases of "idiopathic" acute pancreatitis. Intra-acinar activation of trypsinogen plays a central role in the pathogenesis of acute pancreatitis, resulting in subsequent activation of other proteases causing the subsequent cell damage. Ischemia/reperfusion injury is increasingly recognized as a common and important mechanism in the pathogenesis of acute pancreatitis and especially in the progression from mild edematous to severe necrotizing form. Increased intracellular calcium concentration also mediates acinar cell damage. Oxygen-derived free radicals and many cytokines (e.g., interleukin [IL]-1, IL-6, IL-8, tumor necrosis factor-alpha, platelet activating factor) are considered to be principal mediators in the transformation of acute pancreatitis from a local inflammatory process into a multiorgan illness.

The rat pancreas ultrastructure was examined 6, 12, and 18 h after (1) taurocholate-induced acute pancreatitis and after (2) pancreatitis preceded 6 h earlier by intragastric acute 40% ethanol ingestion (5 g/kg b.w.). Pancreatic specific trypsin activity and plasma alpha-amylase were assayed at the same time intervals. The antecedent acute ethanol ingestion resulted in the evident aggravation of pancreas ultrastructural alterations. Acute pancreatitis preceded by ethanol resulted in the increase of zymogen granules number, RER channels were more irregularly distributed, autophagosomes were more abundant and degeneration of mitochondria was more advanced when compared to acute pancreatitis without ethanol ingestion. Tryptic activity increased to higher degree in all pancreatitis groups preceded by ethanol, but this difference was statistically significant (P < 0.01) only after 18 h. These morphological (but not biochemical) differences progressed 12 h after pancreatitis induction. After 18 h of acute pancreatitis the number of zymogen granules decreased in previously alcoholized rats, but tryptic activity remained twofold higher that in animals not given ethanol. Other signs of cellular impairment were still more prominent in alcoholized rats. The obtained results suggest that even single acute ethanol abuse prior to acute pancreatitis does aggravate the morphological and biochemical lesions observed in this disease with possible negative consequences for the prognosis.

The direct effect of free oxygen radicals, if any, on the morphology of the pancreas has never been studied in vivo. This study was designed to evaluate the effects of hydrogen peroxide (H2O2) on permeability of the main pancreatic duct (MPD) and morphology of pancreas in cats when administered intraductally or intraarterially.

Thirty-six mongrel cats were randomly allocated into three groups, and all groups were divided into two subgroups. In group I and III, MPD was perfused with either standard perfusate (group IA and IIIA) or H2O2 at a concentration of 150 microM (group IB and IIIB) for 3 hours. In group II, the splenic artery was infused either with 0.9% sodium chloride (group IIA) or H2O2 (group IIB) for 3 hours. After 3 hours, in group I and II, MPD was perfused with 99mTc labelled dextran, and the percentage of the dextran permeated from the MPD into the portal vein was calculated for the evaluation of the pancreatic duct permeability. Then, tissue samples were obtained for the examination of early histopathological changes in pancreas. In group III, following ductal perfusion studies, the cats were allowed to recover. After 24 hours animals were killed, and samples were taken for the examination of late histological changes in pancreas. In all groups, an inflammatory score was created for each animal based on the pathological changes in pancreas: edema, leukocyte infiltration, parenchymal necrosis, and hemorrhage.

Group I: All cats developed acute edematous pancreatitis with significantly higher inflammatory scores than controls (P < 0.01). Desquamation of the single layer of columnar epithelium that normally lined the duct and leukocyte infiltration around the MPD duct were found. Pancreatic duct permeability was found to be increased significantly (P < 0.01). Group II: There were no statistical differences in inflammatory scores and pancreatic duct permeability between experimental and control groups (P > 0.05). Group III: All animals developed gross acute edematous pancreatitis after 3 hours of intraductal H2O2 perfusion. Histopathological changes at 24 hours were much more pronounced in group IIIB than in group IIIA including focal necrosis and hydropic degeneration of acinar cells.

This study has shown that intraductal H2O2 perfusion induced acute edematous pancreatitis with marked histopathological changes and increased pancreatic duct permeability in cats. Intraarterial H2O2 infusion, however, has no effect on the permeability of the MPD and morphology of pancreas in our model.

The objective of this study was to investigate the effects of ethanol on pancreatic blood flow and interstitial pH in chronic pancreatitis.

Ethanol is known to contribute to the development of both acute and chronic pancreatitis. However, it is unclear how ethanol precipitates episodes of acute pancreatic inflammation in the setting of chronic pancreatitis. In a model of chronic pancreatitis in cats, it is known that pancreatic blood flow is abnormally low and decreases further after ethanol ingestion. Because it is possible that this reduction in blood flow might be damaging to the pancreas, we investigated the effects of ethanol on pancreatic interstitial pH, an index of pancreatic ischemia.

In normal cats and cats with obstructive chronic pancreatitis, pancreatic blood flow and interstitial pH were measured using the hydrogen gas clearance technique and pH microelectrode, respectively.

In normal cats, intragastric, but not intravenous, ethanol reduced both pancreatic blood flow by 62% (p < 0.05) and interstitial pH (7.38 +/- 0.03 to 7.20 +/- 0.03, p < 0.05). In cats with chronic pancreatitis in which basal pancreatic blood flow was already only 60% of normal flow, both intragastric and intravenous ethanol decreased both pancreatic blood flow (intragastric, 40% decrease, p < 0.05; intravenous, 34% decrease, p < 0.05) and interstitial pH (intragastric, 7.24 +/- 0.04 to 7.08 +/- 0.04, p < 0.05; intravenous 7.20 +/- 0.08 to 7.07 +/- 0.07, p < 0.05).

This profound decrease in pH, lasting up to 2 hours after ethanol exposure in the chronic pancreatitis animals, suggests the possibility of ischemic cellular damage to the pancreas. These findings may explain the pathogenesis of bouts of acute pancreatic inflammation after ethanol ingestion in the setting of chronic disease.

The pancreatic damage initiated via different pathogenetic pathways can be increased by triglycerides. Thus, triglycerides seem to play an important role in the pathogenesis of acute pancreatitis.

Lipolytic enzymes and their substrates may play a role in the pathogenesis of acute necrotizing pancreatitis. We investigated, therefore, whether triglycerides alter the course of acute pancreatitis in three experimental models of rats.

1. Edematous acute pancreatitis induced by repeated sc injections of cerulein; 2. Necrotizing acute pancreatitis by retrograde duct injection of sodium taurocholate; and 3. Pancreatic edema by ligation of: a. The bile duct at the liver hilus; b. The common bile/pancreatic duct close to the duodenal wall; or c. A combination of a. and b. Six hours later, rats were sacrificed and the isolated perfused pancreas prepared. The pancreases were perfused with either HEPES/Ringer/HAES alone or in combination with various concentrations of triglycerides (1-5% wt/vol). The activities of lipase and amylase in the portal venous effluents were regarded as a marker of pancreatic injury. In addition, the pancreases were evaluated by light microscopy.

In both cerulein and taurocholate acute pancreatitis, amylase/lipase activities were significantly higher compared to controls during 45 min of perfusion. In both models, addition of triglycerides caused a dose-dependent marked elevation of enzymes. Ligation (a) did not cause any rise in enzymes in the venous effluent; triglycerides had no effect. Ligation (b) or (c) caused a significant increase of pancreatic enzymes, which was further increased by triglycerides. Histology showed various degrees of severity of tissue damage depending on the model used. The additional damaging effect of a 45-min perfusion with triglycerides, however, could not be detected by histology.

When taurocholate was injected into the common bile duct, high ductal pressure due to ligation of the pancreatic duct did not produce more damage in the pancreas of both old rats and young adult rats, and levels of pancreatic enzymes in portal venous effluent were lower in old rats than in younger rats.

The effects of ligation of the pancreatic duct and aging on acute pancreatitis caused by taurocholate are still unclear.

Young adult and old male Wistar rats were used. Six hours after ligation of the common bile duct in both the duodenum and liver hilus, rats were killed and the pancreata were perfused. Taurocholate or normal saline was injected retrogradely into the common bile duct. The levels of amylase and lipase in the portal venous effluent were determined as markers of damage to the pancreas. The pancreas was also histologically examined after the perfusion experiments using an Image Analysis System.

(1) A nonsignificant elevation of pancreatic enzymes was found in portal venous effluent by the retrograde injection of saline into the common bile duct. Injection of taurocholate caused a marked elevation of enzymes in the effluent for the first 30 min after injection, which then gradually decreased. (2) Basal levels of pancreatic enzymes were significantly higher in the ligation group than in the nonligation group. Injection of saline into the common bile duct had no apparent effect on enzymes in the effluent. In contrast, taurocholate injection into the common bile duct produced a marked increase in enzymes in the portal venous effluent. However, no significant difference was found between the ligation group and the nonligation group. (3) Similar findings were obtained when old rats were used. (4) Although basal levels of enzymes were almost the same in nonligated old and young adults rats, taurocholate injection into the pancreatic duct in old rats resulted in a significant depression of enzymes compared to that in young adult rats. In the ligation group, pancreatic enzymes in the portal venous effluent following taurocholate injection tended to be lower in old rats than in young adult rats. The results were histologically supported in that various degrees of fibrosis were found in the pancreata of old rats.

In order to reproduce what might occur during the initial phase in some cases of acute alcohol-induced pancreatitis, rabbits were infused with diluted ethanol and low-dose cerulein. The duct permeability was assessed by recovery of fluoresceinated dextran (molecular weight 19,500) in central venous blood following orthograde duct perfusion with this substance in the anesthetized animal. Serum ethanol, lipase, and amylase were measured; pancreatic duct morphology was examined by light microscopy and electron microscopy. ATP and glutathione were measured, as were amylase, trypsinogen/trypsin, cathepsin B, and DNA levels in differential centrifugates. As expected, acinar amylase and trypsinogen showed a significant decrease in the experimental group; cathepsin B activity was similarly diminished. Compared with the control group, the activity of serum amylase and lipase in the experimental group demonstrated a significant increase. However, no differences between saline-infused control animals and the treated group regarding pancreatic duct permeability, continuity of lumen-lining epithelium, ATP and glutathione levels, and the relative subcellular distribution of pancreatic digestive and lysosomal enzymes were observed. Thus, our findings do not support the relevance of some of the most common hypotheses on the pathophysiology of acute pancreatitis in its early stage for at least a certain subgroup of patients with acute alcohol-induced pancreatitis.

Acute oedematous pancreatitis and acute haemorrhagic pancreatitis were studied using the low pressure duct perfusion models of alcoholic pancreatitis in cats. After creating either form over 24 hours, each pancreas was histologically graded and assigned an inflammatory score (0-16; absent-severe). Urinary trypsinogen activation peptide concentrations were also used as a measure of severity. Using the model of acute haemorrhagic pancreatitis, it was previously shown that low dose dopamine (5 micrograms/kg.m) reduced the inflammatory score at 24 hours and that this effect was mediated by a reduction in pancreatic microvascular permeability acting via dopaminergic and beta adrenergic receptors. Further studies were conducted and are reported here. In experiment 1 different doses of dopamine in established alcoholic acute haemorrhagic pancreatitis were studied. In group 1 control cats (no dopamine), the inflammatory score was 10.5 (interquartile range (IQR)4). In groups 2, 3, and 4, haemorrhagic pancreatitis was induced. Twelve hours later dopamine was infused for six hours, in the doses of 2 micrograms/kg.min, 5 micrograms/kg.min, and 50 micrograms/kg.min respectively. The inflammatory score in group 2 was 7 (IQR 0.5, p < 0.05 v group 1), in group 3 it was 7 (IQR 2, p < 0.05 v group 1), and in group 4 it was 7 (IQR 4, p < 0.05 v group 1). This was matched by significantly lower levels of urinary tripsinogen activation peptide at 24 hours. In experiment 2 (group 5) we tried to reduce microvascular permeability further by combining dopamine with antihistamines, but there was no improvement in the inflammatory score. As oedematous pancreatitis is the commoner and milder form of acute pancreatitis in clinical practice, in experiment 3 we looked at the effect of dopamine in this model. In group 6 control cats (no treatment), the inflammatory score was 7 (IQR 3, p < 0.05 v group 1). In group 7 cats given dopamine (5 micrograms/kg.min for six hours) from 12 hours after the onset of actue oedematous pancreatitis, the inflammatory score was reduced to 4(IQR 2, p < 0.05 v group 6). This was matched by a significant reduction in the 24 hour urinary tripsin activation peptide concentration.

The effects of intravenous ethanol and ethanol plus furosemide on pancreatic capillary blood flow (PCBF) were investigated using a laser-Doppler flowmeter. Forty Sprague-Dawley male rats were divided into 4 groups: (1) control, (2) 80% ethanol, (3) 80% ethanol plus furosemide, and (4) furosemide. Mean arterial blood pressure and heart rate were monitored. Levels of serum amylase, calcium, electrolytes, ethanol, and furosemide (groups 3 and 4) were measured, and samples of pancreatic tissue were obtained. The ethanol and furosemide levels were statistically different (p < 0.05). PCBF significantly decreased (p < 0.05) in group 2, increased (p < 0.05) in group 3, and did not differ (p > 0.05) between groups 1 and 4. Histopathologic analysis revealed swollen acini in group 2 and sparse focal necrosis without acinar swelling in group 3. The depressant effect of ethanol on PCBF may be the result of its direct action on pancreatic cells causing edema and capillary compression rather than on primary vascular control mechanisms that adjust blood flow. Furosemide counters this effect.

This study evaluated the effect of operative drainage of the main pancreatic duct (MPD) on functional derangements associated with chronic pancreatitis (CP).

The author previously reported delayed functional impairment in an evaluation of the impact of operative drainage in patients with CP. The author now reports on a prospective study of 143 patients with this diagnosis.

Each patient underwent 1) ERCP, 2) the Bentiromide PABA, 3) 72-hour fecal fat test, 4) oral glucose tolerance test (OGTT) and 5) fat meal (LIPOMUL)--stimulated pancreatic polypeptide release (PP). All patients were stratified as mild/moderate (M/M) or severe CP on the basis of a 5-point system that was developed by the author. Patients were studied at 16-month intervals.

All 143 patients underwent initial and follow-up evaluations in a mean follow-up of 47.3 months; 83 of 143 patients had M/M grade at initial evaluation. Eighty-seven patients underwent (MPD) decompression to relieve abdominal pain. In a separate prospective 17 patients with a diagnosis of CP, a grade of M/M and non-disabling abdominal pain were randomized to operative or non-operative treatment; 9 of these randomized patients were operated upon and 8 were not. No patient improved their grade during follow-up; 47 of 83 M/M patients had operative drainage and 36 did not. This grade was preserved in 41 of 47 (87%) operated patients but in only 8 of the 36 non-operated patients (22%). In the randomized trial, seven of nine operated patients retained their functional status in follow-up, whereas only two of eight patients (25%) randomized to non-operation preserved their functional grade.

These data in this large study as well as among a previous randomized sample, support a policy of early operative drainage before the development of irreversible functional impairment in patients with chronic pancreatitis and associated dilation of the main pancreatic duct.

Lipolytic enzymes may play a role in the pathogenesis of acute pancreatitis. Therefore, the effects of a lipase inhibitor, THL (tetrahydrolipstatin), a protease inhibitor, FUT (nafamostat mesilate), and albumin under different conditions in rats were investigated. (a) Isolated pancreatic acini were incubated with pancreatic homogenates and triglycerides or lecithin with or without albumin and the degree of cellular destruction quantitated. (b) Taurocholate was injected into the pancreatic duct of isolated pancreas and the organ continuously perfused with either FUT, THL, or albumin. Organ damage was evaluated by measurement of pancreatic enzymes in the portal effluence. (c) Necrotizing pancreatitis was induced in vivo via retrograde taurocholate injection. FUT, THL, or albumin was applied either intravenously or injected into the pancreatic parenchyma. (a) Albumin prevented the cellular damage caused by both fatty acids and lysolecithin. (b) THL was ineffective, FUT lowered the release of pancreatic enzymes into the portal effluence, and albumin was most effective. (c) Albumin prevented the development of panlobular necrosis and lowered the degree of extrapancreatic fat necrosis. Albumin, via its ability to bind detergents, may have therapeutic implications.

We have recently reported that lipase may play a role in the pathogenesis of acute pancreatitis by its ability to release fatty acids from triglycerides. The aim of this study was to further investigate the effect of lipase and its various digestive products on the integrity of isolated pancreatic rat acini. Pancreatic acini were prepared by collagenase digestion and their newly synthesized proteins labeled with 35S-methionine. Acini were later incubated in buffer to which various factors were added: Products of lipolytic digestion, such as various fatty acids and monoglycerides, fat tissue, nonactivated or trypsin activated homogenized pancreatic tissue, and a specific lipase inhibitor (THL, tetrahydrolipstatin). Cellular destruction was quantified by the degree of radiolabeled proteins released. Short chain fatty acids and monoglycerides (up to C-12) caused cellular destruction, whereas long chain fatty acids and their respective monoglycerides were not harmful. With regard to unsaturated fatty acids, long chain fatty acids (C-18 to C-22) were also able to destroy cells. The degree of cellular necrosis correlated with incubation time and fatty acid concentration. The cellular damage caused by incubation of acini with either inactive or trypsin activated pancreatic homogenates together with triglycerides could be completely inhibited by the specific lipase inhibitor THL. Bile alone caused no damage. When bile was combined with activated-pancreatic homogenates, about 25% of newly synthesized proteins were released by acini within 30 min. Incubation with a combination out of bile activated pancreatic homogenates and triglycerides resulted in the most pronounced damage. This acinar destruction could only be partly inhibited by THL. These studies suggest that both lipase and phospholipase-A2 may play an important role in the pathogenesis of acinar cell destruction.

We reviewed our experience with 90 patients with pancreatic pseudocysts to determine if the cause of pancreatitis influenced the patients' outcome. Acute pancreatitis (AP) occurred in 57 (63%) patients due to alcoholic (n = 15), postoperative (n = 14), biliary (n = 12), and other etiologies (n = 16). Thirty-three (37%) patients had chronic pancreatitis (CP) secondary to alcohol use (n = 27) or other causes (n = 6). Multiple pseudocysts were significantly more frequent in patients with acute alcoholic pancreatitis than in patients with chronic pancreatitis (47% versus 19%, p < 0.05). Spontaneous resolution occurred within 8 weeks in 10 (11%) patients with pseudocysts (AP = 9%, CP = 15%, p = NS). However, no patient with pseudocyst associated with biliary or postoperative pancreatitis underwent spontaneous resolution. Although pseudocysts associated with chronic pancreatitis were smaller in size (8.0 +/- 4.7 versus 5.7 +/- 3.8 cm, p < 0.05), a similar proportion of them required operation compared with AP pseudocysts (56% versus 58%). There were significantly more deaths in patients with postoperative pancreatitis compared with all other groups (29% versus 7%, p < 0.05). The outcome of pseudocysts was similar regardless of size (greater than 6 cm versus less than 6 cm) and presentation (acute versus delayed). Thus, the etiology of pancreatitis was a more important determinant of pseudocyst outcome than pseudocyst size or presentation.

Hemorrhagic pancreatitis was induced in cats by perfusing pancreatic enzymes through a pancreatic duct after the administration of intragastric ethanol. Dimethyl prostaglandin E2 was administered concurrently. In the first study, dopamine's antiinflammatory effect on the pancreas was determined in the presence of haloperidol, propranolol, or both. Next, dopamine's effects on blood flow in the normal and inflamed pancreas were compared using a hydrogen gas-clearance technique. In the final study, the effect of dopamine on fluorescein isothiocyanate-labeled dextran leakage from the pancreatic duct to portal venous blood was investigated. It was found that blockade of either dopamine or beta-adrenergic receptors reduced, and blockade of both receptors completely eliminated, the antiinflammatory effect. Dopamine had no effect on pancreatic blood flow in normal cats. In pancreatitis, although dopamine transiently reduced blood flow, after an hour flow had returned to normal. Dopamine reversed the leakage of fluorescein isothiocyanate-labeled dextran from the pancreatic duct caused by ethanol and by ethanol and prostaglandin E2. It was concluded that dopamine ameliorated pancreatitis by reducing pancreatic ductal and/or microvascular permeability rather than by altering pancreatic blood flow. The antiinflammatory effect was mediated by both dopamine and beta-adrenergic receptors.

Somatostatin, originally detected by Krulich and ultimately isolated by Brazeau, was initially described as a growth hormone release-inhibiting factor. Subsequent investigation into the use of native somatostatin and the development of long-acting somatostatin analogues, especially octreotide acetate, have fostered increasing uses of these compounds. Though the clinical and investigational uses of somatostatin and its analogues are varied, one central theme remains constant: the ability of these agents to suppress circulating peptide levels. This article, a review of the current non-endocrine applications of somatostatin and its analogues, covers a wide range of potential applications for somatostatin-like compounds. These include use in cirrhosis and variceal bleeding, peptic ulcer disease, pancreatic fistulas, acute and chronic pancreatitis, dumping syndrome, cancer therapy, small bowel fistulas, psoriasis, pain control, and autonomic hypotension. Somatostatin may also play a role in the development and potential treatment of neurologic disease and may have profound found influence on behavior.

We studied the conversion of acute edematous pancreatitis (AEP) to acute hemorrhagic pancreatitis (AHP) in an experimental model in cats. In the model, 16,16 dimethyl PgE2 effects this conversion by increasing microvascular permeability. First, we induced AEP in cats and then gave PgE2 at increasing intervals after the induction of AEP to see how long an interval would still allow conversion. In 6 groups of cats, PgE2 was administered for 2 h, starting at 2, 4, 6, 8, 10, or 12 h after the creation of AEP. Twelve h later, the cats were sacrificed and the pancreases were graded for inflammation and hemorrhage. Significant pancreatic hemorrhage did not occur when the PgE2 was administered at 12 h compared to 2 h. Next, we determined that PgE2 still retained its ability to increase pancreatic vascular permeability when administered 12 h after the creation of AEP. This was done by perfusing a marker molecule through the MPD (fluorescein isothiocyanate labeled dextran: FITC-D, mol wt 20,000) and then finding it in portal venous blood (PVB). The presence of FITC-D in PVB signified increased vascular permeability, since normally none was present. We concluded that conversion of AEP to AHP was possible during the first 12 h after induction of AEP. Lack of conversion at 12 h was not caused by a lack of vascular reactivity at that time.

Six patients with a drain in the main pancreatic duct were studied. Ethanol was given orally with individually adjusted doses aiming at a blood value of 0.8/1000 (17.6 mmol/l). Concentrations of ethanol in venous blood and pancreatic juice were recorded for three hours. Similar studies were made when ethanol was administered as an intravenous priming dose followed by a maintenance infusion. After orally administered ethanol, pancreatic juice values were higher than those in blood for a short period of time. The relations between median concentrations and time were incongruous curves consistent with a significant treatment by time interaction. Intravenous administration resulted in a similar pattern, but the interaction was not statistically significant. These findings indicate that the human pancreas may secrete ethanol.

Acute hemorrhagic pancreatitis (HP) is probably associated with decreased blood flow in its early phases, as well as with an increase in microvascular permeability. Dopamine (DOP; 5 micrograms/kg-min) is a splanchnic vasodilator, and also has beta-adrenergic effects that can prevent increases in microvascular permeability. We hypothesized that low dose dopamine might have beneficial effects on both blood flow and microvascular permeability, thus ameliorating the severity of the disease. We studied its actions in an animal model of HP. In anesthetized cats, intragastric ethanol (20 ml/40% solution) rendered the main pancreatic duct permeable to pancreatic enzymes. Then the duct was perfused from tail to head with 0.5 ml of activated pancreatic enzymes for 1 hr. To create HP, 16,16-dimethyl prostaglandin E2 (2 micrograms/kg-hr, iv) was given for 2 hr to increase blood flow and microvascular permeability. Seven of eight cats developed HP in 24 hr. Control cats received no additional drugs. Two experimental groups received DOP (6 hr infusion) begun either (1) at the onset of enzyme perfusion or (2) 12 hr later. Each pancreas was examined after 24 hr and graded (1-4) histologically for edema, hemorrhage, polymorphonuclear cell infiltrate, and architectural loss. An inflammatory score (IS) from 0 to 16 was thus created (higher scores = greater damage). The results showed an IS of 10.9 +/- 1.8 for the controls, 3.3 +/- 0.5 for the immediate treatment group, and 7.2 +/- 1.8 for the delayed treatment group. Both treated groups had a significantly better IS (t tests, P less than 0.001 and P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)