Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1389183 (autodigestion)
 317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial biopsies from two patients who had developed "stone heart" (myocardial rigor mortis; ischemic contracture of the left ventricle) were studied by electron microscopy. The ultrastructure of tissue in stone heart, though ischemic in nature, differed from that of classic myocardial infarction in some respects. Apart from depletion of glycogen and distension of the sarcoplasmic reticulum and T-tubules, myofibrillar degeneration was much more widespread. Mitochondrial degeneration with active lysosomal autodigestion, disruption of the microcirculation, and lymphedema were prominent changes also observed. In the light of known clinical and experimental observations, our findings suggest that stone heart is an accelerated form of ischemic injury occurring in vulnerable (hypertrophied) hearts and is probably related to ischemia-triggered release of endogenous catecholamines.
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PMID:Ultrastructure of ischemic contracture of the left ventricle ("stone heart"). 99 57

In pathogenic studies on acute pancreatitis the importance of a temporary ischemia on induction of autodigestion was demonstrated. Because of the involvement of oxygen-derived free radicals in the ischemia/reperfusion injury of other tissues we have investigated the influence of artificial oxidants, as FeCl3 and H2O2, on pancreatic tissue and isolated pancreatic acinar cells. Lipid peroxidation was determined as thiobarbituric-acid-reactive substances (TBRS). In these experiments the TBRS concentration was elevated within the first min of incubation with FeCl3. The exposure of pancreas homogenates and intact acinar cells to H2O2 had no remarkable effect on formation of TBRS. Under this condition the survival of cells was strongly reduced, while cells exposed to FeCl3 revealed a remarkably slower rate of cytolysis. The missing correlation between cell lysis and elevation of TBRS suggests that lipid peroxidation might not be essential process in pancreatic acinar cell damage.
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PMID:Studies on lipid peroxidation in pancreatic tissue. In vitro formation of thiobarbituric-acid-reactive substances (TBRS). 191 59

To study the dynamics of pathomorphologic alterations in the development of acute pancreatitis (AP) and the corresponding changes of the patterns of pancreatic enzymes in rats AP was induced by: 1) combination of a pancreatic juice edema and temporary pancreatic ischemia, ii) by intraductal instillation of trypsin, and iii) by trypsin instillation in combination with ischemia. At 4, 8 and 24 h postoperatively the histologic findings and the activities of lipase and alpha-amylase in the pancreas and the serum were analyzed. The histologic sum score of the individual rats did not correlate with their enzymic patterns in pancreas and in serum. In all three models there was a development of parenchymal necrosis independent of the existence of pancreatic fat necrosis. Therefore, it is not probable that fat necrosis represents an obligatory precondition for the initiation of autodigestion.
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PMID:Experimental acute pancreatitis--a quantification of dynamics at enzymic and histomorphologic levels. 281 89

Six cases of severed intestines in farm-raised channel catfish were examined at fish disease diagnostic laboratories in Mississippi and Alabama. This condition has not been reported previously in fish. Affected fish had a 4-7-cm-long intestinal section (hyperemic where it was severed) attached to the stomach. The remainder of the intestine was completely missing in all six cases except for a 1-1.5-cm section of intestine prolapsed from the anus in fish from three of the cases. Ischemia, autodigestion following intussusception, or intestinal epithelium degradation are suggested as possible etiologies for this condition.
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PMID:Severed intestine in channel catfish. 335 84

The effects of several pancreatic enzymes on living tissue incapable of autodigestion were studied to analyse elements of the "pluralistic events of acute hemorrhagic pancreatitis" (Becker 1981). Phospholipase A2 induces (via toxic lysolecithin) cytotoxic necrosis in the testis; elastase (via destruction of vessels and local ischemia) causes hypoxic necrosis. Injection of lipase does not result in necrosis.
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PMID:Investigations into various pancreatic enzymes. 692 26

Apoptosis is a tightly regulated, energy-requiring process of programmed cell death. While necrosis is a form of cell death that results from acute cellular injury, apoptosis is controlled autodigestion of the cell that occurs through activation of endogenous proteases. This process results in the cleavage of chromatin into oligonucleosome-length DNA fragments and its multiples. This DNA fragmentation demonstrates a characteristic laddering pattern on DNA agarose gel electrophoresis. The heart undergoes extensive remodeling during embryogenesis wherein apoptosis significantly contributes to the development of the cardiac chambers and correct routing of the great vessels. Pathologic stimuli can also result in apoptosis and include ischemia, hypoxia, inflammation, cytokines, growth factors, and toxic agents. Better understanding of the molecular mechanisms responsible for regulating apoptosis in the failing myocardium may soon lead to strategies aimed at preventing further myocyte loss and enhancing myocyte replacement through regulated cell growth.
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PMID:Apoptosis in the failing heart. 989 98

In healthy subjects, the 3 known pancreatic trypsinogens, which are endopeptidases belonging to the chymotrypsin superfamily, are activated by enterokinase and partial autoactivation in the duodenum. The premature activation of trypsinogen in the pancreatic interstitium, with the subsequent activation of other pancreatic zymogens, is believed to lead to the autodigestion of the gland, this being the first event in acute pancreatitis. The mechanisms that lead to trypsinogen, activation in acute pancreatitis are largely unknown. However, ischemia, hypercalcemia and the activation of cathepsin B (by cholecystokinin) are thought to be of importance. The easiest and most reliable way to assess trypsinogen activation is the measurement of the activation peptide, TAP, in urine, plasma, pancreatic tissue or ascitic fluid. In the animal model of acute pancreatitis, TAP in ascites and pancreatic tissue has been shown to correlate with the presence and extent of necroses. It has proven to be a good marker for the severity of pancreatitis and is a useful marker in examining the pathophysiology and possible treatment modalities in the animal model of acute pancreatitis. Studies on TAP in human acute pancreatitis were most commonly focused on urinary TAP. Within a 48-hour time frame after the onset of the disease, TAP was a good predictor of the severity of acute pancreatitis. The main advantage over other markers, such as CRP, is that TAP is the earliest marker of necrosis to be increased. Also, increased levels of TAP in ascitic fluid were shown to correlate well with pancreatic necroses. In our experience, plasma TAP was found to have a "diagnostic window" within the first 3 days predicting pancreatic necroses. Positive TAP gave a very good positive prediction and a high specificity towards the development of pancreatic necroses, but did not differ between necrotizing pancreatitis with systemic complications or uncomplicated necrotizing pancreatitis. We therefore think that plasma TAP is a very good marker for local complication in acute pancreatitis and its routine measurements may help to identify patients at a high risk within the first days of the disease.
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PMID:Mechanism and role of trypsinogen activation in acute pancreatitis. 1057 41

Intestinal ischemia is associated with high morbidity and mortality, but the underlying mechanisms are uncertain. We hypothesize that during ischemia the intestinal mucosal barrier becomes disrupted, allowing digestive enzymes access into the intestinal wall initiating autodigestion. We used a rat model of splanchnic ischemia by occlusion of the superior mesenteric and celiac arteries up to 30 min with and without luminal injection of tranexamic acid as a trypsin inhibitor. We determined the location and activity of digestive proteases on intestinal sections with in situ zymography, and we examined the disruption of two components of the mucosal barrier: mucin isoforms and the extracellular and intracellular domains of E cadherin with immunohistochemistry and Western blot techniques. The results indicate that nonischemic intestine has low levels of protease activity in its wall. After 15-min ischemia, protease activity was visible at the tip of the villi, and after 30 min, enhanced activity was seen across the full thickness of the intestinal wall. This activity was accompanied by disruption of the mucin layer and loss of both intracellular and extracellular domains of E cadherin. Digestive protease inhibition in the intestinal lumen with tranexamic acid reduced morphological damage and entry of digestive enzymes into the intestinal wall. This study demonstrates that disruption of the mucosal epithelial barrier within minutes of intestinal ischemia allows entry of fully activated pancreatic digestive proteases across the intestinal barrier triggering autodigestion.
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PMID:Disruption of the mucosal barrier during gut ischemia allows entry of digestive enzymes into the intestinal wall. 2208 98

The pathophysiologic process of severe acute pancreatitis involves a vicious cycle of inflammation and increasing oxidative stress. Secretory defects trap activated pancreatic enzymes within the gland leading to autodigestion while circulatory abnormalities add the insult of ischemia/reperfusion injury. What may have the greatest impact in amplifying the systemic inflammatory response, though, is intestinal failure with breakdown of gut barrier defenses, subversion of submucosal immune responses, and emergence of a virulent pathobiome. Understanding the intricacies of these changes has broad-reaching implications for nutrition therapy, which should no longer be limited to the provision of early enteral feeding alone. Emerging strategies should attempt to maintain commensalism, bind potential pathogens, refaunate the microbiome, actively turn off inflammation, reset cross-talk signaling with epithelial receptors, and deliver nutrients further down the gastrointestinal tract to the level of greatest microbial burden. Innovative nutrition therapy for the patient with severe acute pancreatitis should be designed to address and include all of these strategies in order to shift the course of clinical outcome toward a pattern of recovery and homeostasis.
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PMID:Factors That Worsen Disease Severity in Acute Pancreatitis: Implications for More Innovative Nutrition Therapy. 3133 59