Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001339 (acute pancreatitis)
 10,593 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A surgical method is described which allows in vivo assessment of reversible rat pancreatic ischemia using 31P NMR spectroscopy at 2.0 T. Phosphorous-31 NMR spectra acquired during the ischemic period show the expected increase in inorganic phosphate with a concomitant decrease in ATP levels and pH as compared to controls. Upon reperfusion, inorganic phosphate and ATP returned to control levels while pH recovered to a more alkaline value. This method provides a means of studying in vivo changes in high energy metabolite associated with acute pancreatitis (AP) and maintains the secretory ability of the gland so that different forms of AP, such as those arising from pancreatic juice edema, can be studied.
 ...
PMID:A method for in vivo assessment of reversible rat pancreatic ischemia using 31P NMR spectroscopy at 2.0 tesla. 779 56

Multiple organ failure is the most common cause of death in critically ill patients in the United States. Acute respiratory failure is the most important single component of this clinical scenario, with a mortality risk > 50%. Key pathophysiologic events occur in the pulmonary microvasculature at the interface between circulating elements and the external environment. In particular, the response of the alveolar capillary endothelial cell is of fundamental importance in this injury process. A variety of clinical stimuli initiate a systemic inflammatory response that contributes to acute microvascular lung injury. Sepsis, trauma, thermal injury, acute pancreatitis, and ischemia-reperfusion injury are among these stimuli. The particular emphasis of this review is on events associated with intestinal ischemia-reperfusion, a common and important clinical event. The pathogenic mechanisms that lead to acute lung injury in this setting are not completely understood, although it is clear that neutrophil-endothelial interactions regulated by both humoral and local mediators are crucial. Oxygen-derived free radicals, proteases, cytokines, eicosanoids, endotoxin, complement activation products, and probably platelet activating factor and nitric oxide are involved as either signalling or effector molecules. The key cellular participants during the acute phase of injury are the polymorphonuclear neutrophil (PMN) and the microvascular endothelial cell. Each of these participants is considered with regard to phlogistic behavior and the potential for therapeutic intervention. Adherence of the neutrophil to the endothelium creates a microenvironment in which PMN-derived oxidants, proteases, and cationic proteins are discharged under conditions that lead to cellular injury. Loss of microvascular integrity results and pulmonary dysfunction follows. At present, we offer only nonspecific supportive care for patients with this problem. However, investigations into relevant molecular and cellular regulatory events offer important opportunities for directed therapy. We are now approaching the threshold for utilization of several new and specific approaches. While no single pharmacologic therapy is likely to be curative for this complex problem, it is probable that certain approaches will be of clinical benefit in the near future. This review is designed to provide a basis for understanding this evolution.
 ...
PMID:Pulmonary microvascular injury following intestinal reperfusion. 780 96

Due to the complexity of interacting organ systems, in vivo the interpretation of results obtained from whole-animal experiments of acute pancreatitis remains difficult. To enlighten cause-and-effect-relationships, functional isolated parts of the pancreas are applied increasingly in research into the pathogenesis of the disease, therefore. By means of a collagenase digestion technique, intact acinar cells from normal as well as from pretreated rat pancreas could reproducibly be obtained in high yield. Animals were pretreated in situ by induction of either mesenteric ischemia/reperfusion, juice edema, or acute pancreatitis (AP). Pancreatic acinar cells isolated from these pretreated rats consumed oxygen at comparable rates under resting conditions throughout all experimental groups. A reduced stress capacity of cell respiration as well as a preterm decline in short-term culture was observed in the cells of the AP group, however. These results demonstrate that the induction of AP has found its reflection within the acinar cells themselves. Interestingly, these effects were not clouded by the isolation procedure. The manner of in-situ pretreatment of the respective animal proved to be decisive for later viability of isolated acinar cells in short-term culture. Uncoupling of oxidative phosphorylation by 2,4-dinitrophenol (DNP) lead to an accelerated decline of the acinar cells in all groups. The intactness of cellular energy metabolism seems to play a crucial role in maintaining cellular integrity, therefore. In additional experiments in vitro, the intracellularly mediated cell damage by DNP was compared with one induced from the extracellular environment of isolated cells by antibodies directed against cell surface antigens plus complement.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Mechanisms for cell damage in acute pancreatitis using isolated acinar cells]. 784 69

Between 1978 and 1991, 116 of 19,246 patients (0.6%) undergoing cardiac surgery developed abdominal complications (renal/hepatic failure excluded) within 30 days of their cardiac operation. Comparison with a randomly selected control group of 217 patients operated upon over the same period of time was also undertaken. Compared to the control group, the study patients were older (mean age, 63.3 +/- 12.5 years vs 57.5 +/- 21.5 years; P = 0.03), more likely to have a history of alcohol abuse (10% vs 4%; P = 0.03), and more likely to have a previous history of gastrointestinal problems (43% vs 17%; P = 0.0001). There was also a trend towards a greater number of patients having valvular surgery, particularly reoperative surgery, in the study group. Postoperatively, patients with marked low cardiac output, requiring the intra-aortic balloon pump, were more likely to develop abdominal complications. These complications included complicated peptic ulcer disease in 54 (47%), intestinal obstruction and/or perforation in 19 (16%), biliary tract disease in 13 (11%), mesenteric ischemia in 13 (11%), acute pancreatitis in 3 (3%), and miscellaneous complications in the remaining 14 (12%). Forty-three patients were treated medically and 73 patients required operative intervention. The surgical procedures performed were truncal vagotomy and drainage (12), oversewing of a perforation or a bleeding vessel (6), gastrectomy (2), intestinal resection (14), laparotomy only (14), cholecystectomy (14), and other (11). Mortality was 26% (30/116) with the mortality for medical and surgical treatment being 16% vs 32%, respectively (P = 0.112). Intestinal ischemia had the highest mortality, with a rate of 85% (11/13). Despite intensive monitoring and care of cardiac surgical patients, abdominal complications do occur, although rarely. Risk factors include older age, a positive history of gastrointestinal disease, reoperative valve surgery, and severe postoperative low cardiac output.
 ...
PMID:Abdominal complications following cardiac surgery. 820 26

Four models of acute pancreatitis have been previously developed that use the ex vivo perfused isolated canine pancreas preparation. The four models include the intraarterial infusion of oleic acid (FFA) that mimics hyperlipemic pancreatitis, partial obstruction of the pancreatic duct with secretin stimulation (POSS) that mimics gallstone pancreatitis, a 2-hour period of ischemia before perfusion (ISCH 2) that mimics shock pancreatitis, and the infusion of cerulein at supramaximal stimulatory doses (CER), which lacks an obvious clinical counterpart. In the FFA, POSS, and ISCH 2 pancreatitis, but not in the CER pancreatitis, toxic oxygen metabolites, generated by the enzyme xanthine oxidase (XO), have been shown to be important mediators in the early pathogenesis. Ordinarily XO primarily occurs as xanthine dehydrogenase (XD) but can be converted to XO, which is the form that generates toxic oxygen metabolites. This conversion of XD to XO may take place either reversibly by way of sulfhydryl group oxidation or irreversibly by means of proteolytic cleavage of XD. This study was undertaken to investigate the mechanism of conversion of XD to XO in the FFA-, POSS-, and ISCH 2-induced pancreatitis models. CER pancreatitis was studied for comparison. After 4 hours of perfusion, pancreatitis was manifest by edema, weight gain, and hyperamylasemia in all four models. Dithiothreitol, a sulfhydryl group protector, ameliorated the weight gain in the FFA (40 +/- 14 gm to 18 +/- 13 gm; p < 0.05), POSS (28 +/- 10 gm to 9 +/- 3 gm; p < 0.05), and ISCH 2 pancreatitis (30 +/- 13 gm to 15 +/- 3 gm; p < 0.05), and ameliorated the hyperamylasemia in the POSS pancreatitis (12,062 +/- 4304 units/dl to 5877 +/- 2659 units/dl; p < 0.05). The CER pancreatitis was not ameliorated with dithiothreitol. A serine protease inhibitor of low molecular weight, phenylmethylsulfonyl fluoride, ameliorated only the CER pancreatitis (weight gain from 28 +/- 10 gm to 17 +/- 10 gm, p < 0.05; amylase activity from 38,116 +/- 6491 units/dl to 23,372 +/- 11,654 units/dl, p < 0.05), and not the FFA, POSS, or ISCH 2 pancreatitis. We conclude that in the three models of pancreatitis (FFA, POSS, and ISCH 2) that are mediated by toxic oxygen metabolites, XD is converted to XO reversibly by way of sulfhydryl group oxidation rather than irreversibly by way of proteolysis. In the CER pancreatitis, where XO does not play a role in the pathogenesis, proteolytic enzymes may be important mediators in the injury.
 ...
PMID:The mechanism of conversion of xanthine dehydrogenase to xanthine oxidase in acute pancreatitis in the canine isolated pancreas preparation. 841 95

The current study was done to evaluate the effects of short term (60 minutes) pancreatic biliary duct obstruction (PBDO) with intraductal hypertension (IDH) stimulated by secretin (0.2 clinical unit per kilogram per hour) and caerulein (0.2 microgram per kilogram per hour) plus 30 minutes of temporary pancreatic ischemia (ISCH) produced by ligation of celiac and superior mesenteric artery on the exocrine pancreas and protective effects of a new potent protease inhibitor, ONO3307 in combination with xanthine oxidase inhibitor, allopurinol, in this multifactor related model of acute pancreatitis in rats. Twelve hours after PBDO with IDH plus ISCH, we observed hyperamylasemia (23 +/- 3 units per milliliter) (p < 0.01); moderate pancreatic histologic changes; pancreatic edema (water content--81 +/- 2 percent) (p < 0.02), as well as the impaired amylase (2,889 +/- 328 units per kilogram per hour) (p < 0.01) and cathepsin B output (7 +/- 3 units per kilogram per hour) (p < 0.01) into the pancreatic juice of rats stimulated by caerulein (control group--serum amylase levels, 6 +/- 1 units per milliliter; pancreatic water content, 74 +/- 1 percent. Furthermore, PBDO with IDH plus ISCH caused the redistribution of lysosomal enzyme from lysosomal fraction (12 kilo times gravity pellet; 40 +/- 3 percent; p < 0.01) to zymogen fraction (1.3 kilo times gravity pellet; 38 +/- 3 percent; p < 0.01) (control group--12 kilo times gravity pellet, 59 +/- 2 percent; 1.3 kilo times gravity pellet, 24 +/- 2 percent) and the impaired pancreatic adenylate energy metabolism (0.79 +/- 0.02, p < 0.02) (control group--energy charge equals 0.88 +/- 0.01). Only PBDO with IDH caused no significant changes. Although only ONO3307 or allopurinol therapy showed the partial significant protective effects against pancreatic injuries, improving serum amylase levels, the administration of ONO3307 in combination therapy with allopurinol showed almost complete protective effects against the pancreatic injuries induced by PBDO with IDH plus ISCH (serum amylase levels, 9 +/- 2 units per milliliter; pancreatic water content, 76 +/- 2 percent; amylase and cathepsin B output, 7,127 +/- 946 and 18 +/- 3 units per kilogram per hour; 1.3 kilo times gravity pellet, 28 +/- 2 percent; 12 kilo times gravity pellet, 54 +/- 2 percent, and energy charge equals 0.85 +/- 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Protective effects of therapy with a protease and xanthine oxidase inhibitor in short form pancreatic biliary obstruction and ischemia in rats. 846 Apr 15

Ischemia as a causative factor for acute pancreatitis has been discussed for decades but has only recently gained wider acceptance. Chronic pancreatitis, however, has rarely been attributed to ischemic injury. While experimental evidence is available for the ischemic pathogenesis of acute pancreatitis, no studies have been reported about pancreatic ischemia as a single cause of chronic pancreatitis. Also, the progression from acute to chronic pancreatitis has been a very controversial issue. To address both questions we have injected polystyrene microspheres of 20-microns diameter into the pancreatic branches of the splenic artery of 36 rats. Thirteen more rats were sham operated and injected with saline. The animals were killed at 1, 2, 3, and 9 weeks after operation and macroscopically and histologically examined, and serum alpha-amylase and weight gain were determined. For the pancreas the following parameters were assessed using a score from 0 (no change) to 4 (severe change): atrophy, hemorrhage, edema, fat necrosis, acinar necrosis, polymorphonuclear infiltration, mononuclear infiltration, interstitial fibrosis, and ductal changes. While no difference between control and experiment was observed for serum alpha-amylase, weight gain, edema, and hemorrhage, persistent differences were evident for the parameters characteristic of chronic pancreatitis, most significantly for interstitial fibrosis, ductal changes, mononuclear infiltration, acinar necrosis, and atrophy. No spontaneous deaths occurred. The severity of the lesions remained stationary after the first week. Our work shows for the first time that pancreatic ischemia by microvascular hypoperfusion can cause histopathologic changes characteristic of chronic pancreatitis and that these changes follow acute necrotizing pancreatitis.
 ...
PMID:Does acute pancreatitis progress to chronic pancreatitis? A microvascular pancreatitis model in the rat. 853 54

Based on the concept that ischemia is an important factor in the pathogenesis of acute pancreatitis, we developed a new model of complete ischemia/reperfusion of the pancreas in the rat. The aim of this study was to investigate the microcirculation of the pancreas after complete and reversible ischemia at different times after reperfusion by using intravital fluorescence microscopy. In addition, the effect of ischemia/reperfusion on the pancreas was assessed by means of light and electron microscopy and measurement of serum pancreas amylase concentration. In 35 adult Sprague-Dawley rats ischemia of the pancreas was induced by temporary occlusion of the four supplying arteries. Sham-operated animals served as controls (group A). After periods of 30 min (group B), 60 min (group C) or 120 min (group D) of ischemia the organ was reperfused. To exclude the influence of hypovolemia on microcirculation in group E (120 min ischemia) hydroxyethylstarch (HES) was given i.v. to maintain central venous pressure at baseline values. For intravital fluorescence microscopy the pancreas was exteriorized on a stage and quantitative analysis of microcirculation, including functional capillary density and leukocyte-endothelium interaction, was performed after 30 min, 1 h and 2 h of reperfusion. Serum pancreas-amylase was measured at control (prior ischemia) and at 2 h after reperfusion. Tissue samples for light and electron microscopy were taken 2 h after reperfusion. In sham-operated animals, functional capillary density (FCD) remained within baseline values (FCD 407.7 +/- 9 cm-1) during reperfusion. Dependent on the time of ischemia and time of reperfusion a gradual reduction in functional capillary density was observed; after 2 h of ischemia only 35% of capillaries were perfused (FCD 140.9 +/- 28.3 cm-1). Reduced functional capillary density was associated with an increase of perfusion heterogeneity to a maximum of 0.65 +/- 0.12, as against 0.13 +/- 0.02 in control animals. With a 2 h ischemia leukocyte-endothelium interaction was enhanced after 0.5 h of reperfusion (8-fold increase of adherent leukocytes in comparison to control) followed by a further significant increase until 2 h after the beginning of reperfusion. Amylase concentration after ischemia of 2 h (2967 +/- 289 U/l) was significantly higher as compared to controls (1857 +/- 99 U/l). Differences between group E and D were not observed. Pancreatic tissue injury was ascertained by histopathological studies. These results indicate that complete ischemia/reperfusion of the pancreas induces pancreatic microvascular failure. The severity of changes depends on duration of ischemia and duration of reperfusion. The morphological and biochemical changes suggest that ischemia/reperfusion causes an inflammatory reaction as observed in acute pancreatitis.
 ...
PMID:Ischemia reperfusion of the pancreas: a new in vivo model for acute pancreatitis in rats. 857 Sep 8

With the concept that ischemia-reperfusion injury may contribute to the pathogenesis of acute pancreatitis, we have quantitatively analyzed the pancreatic microcirculation of rats during postischemic reperfusion using intravital fluorescence microscopy. Ischemia to the pancreas of Sprague-Dawley rats (N = 7) was induced by clamping the arteriae gastroduodenalis, lienalis, gastrica sinistra, and gastricae breves for 60 min followed by 120 min of reperfusion. Ischemic conditions were verified by measurement of microvascular hemoglobin oxygenation using reflection spectrophotometry (n = 9). Postischemic reperfusion was characterized by a significant (P < 0.05) reduction of functional capillary density to approximately 69% of baseline (no reflow). Reperfusion-induced inflammatory response was reflected by a marked increase (100-fold; P < 0.01) of the number of permanently adherent leukocytes in postcapillary venules (reflow paradox). Postischemic reperfusion was further associated with increased serum lipase activities, and histomorphological analysis revealed alterations, similar as known in acute interstitial pancreatitis, ie, neutrophil infiltration, interstitial edema, and hemorrhagic lesions. We, therefore, conclude that ischemia-reperfusion- associated events, ie, no reflow and reflow paradox, may be considered as trigger mechanisms in the manifestation of distinct types of acute pancreatitis, in particular posttransplant pancreatitis.
 ...
PMID:Ischemia-reperfusion-induced pancreatic microvascular injury. An intravital fluorescence microscopic study in rats. 862 48

Gastrointestinal problems, with an incidence of about 1%, may complicate the postoperative period after cardiovascular surgery, increasing morbidity, length of stay, and mortality. Several risk factors for the development of these complications, including preexisting conditions; advancing age; surgical procedure, especially valve, combined bypass/valve, emergency, reoperative, and aortic dissection repair; iatrogenic conditions; stress; ischemia; and postpump complications, have been identified in multiple research studies. Ischemia is the most significant of these risk factors after cardiovascular surgery. Mechanisms that have been implicated include longer cardiopulmonary bypass and aortic cross-clamp times and hypoperfusion states, especially if inotropic or intra-aortic balloon pump support is required. These risk factors have been linked to upper and lower gastrointestinal bleeding, paralytic ileus, intestinal ischemia, acute diverticulitis, acute cholecystitis, hepatic dysfunction, hyperamylasemia, and acute pancreatitis. Gastrointestinal bleeding accounts for almost half of all complications, followed by hepatic dysfunction, intestinal ischemia, and acute cholecystitis. Identification of these gastrointestinal complications may be difficult because manifestations may be masked by postoperative analgesia or not reported by patients because they are sedated or require prolonged mechanical ventilation. Furthermore, clinical manifestations may be nonspecific and not follow the "classic" clinical picture. Therefore, astute assessment skills are needed to recognize these problems in high-risk patients early in their clinical course. Such early recognition will prompt aggressive medical and/or surgical management and therefore improve patient outcomes for the cardiovascular surgical population.
 ...
PMID:Acute gastrointestinal complications after cardiac surgery. 865 62


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>