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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the effects of acute pancreatitis on the energy metabolism of the liver and on the fragility of hepatic cells and subcellular organelles, we studies (1) the arterial blood ketone body ratio (BKBR) (aceto acetate/beta-hydroxy butyrate), which is in equilibrium with the free NAD+/NADH ratio in liver mitochondria; (2) the hepatic energy charge (EC) = (ATP + 1/2 ADP)/(ATP + ADP + AMP); (3) the cathepsin B leakage from hepatic lysosomes and the malate dehydrogenase leakage from hepatic mitochondria in vitro; and (4) the protective effects of prostaglandin E2 (PGE2) and a new synthetic protease inhibitor ONO 3307 on hepatic injury in acute pancreatitis induced in rats by a supramaximal dose of caerulein. Decreased BKBR and hepatic EC as well as increased hepatic lysosomal and mitochondrial fragility were observed in rats with this type of acute pancreatitis, and both PGE2 and ONO 3307 had a significant protective effect against hepatic injury in these rats, especially ONO 3307. These results suggest that impaired hepatic energy metabolism is closely related to increased hepatic lysosomal and mitochondrial fragility and that some proteases, which are derived from pancreatitis and are susceptible to inhibition by ONO 3307, seem to play an important pathological role in this liver injury induced by pancreatitis. Therefore, it is important to take care of the liver in patients with acute pancreatitis.
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PMID:Impaired hepatic energy metabolism in rat acute pancreatitis: protective effects of prostaglandin E2 and synthetic protease inhibitor ONO 3307. 152 49

Assessment of viability of a pancreas graft during preservation is very important to avoid transplantation of a nonfunctioning allograft. In the present report the correlation between adenosine triphosphate tissue concentration at the end of cold preservation by the two-layer method and viability a of canine pancreas graft following transplantation was studied. After preservation by an original two-layer (Euro-Collins' solution/perfluorochemical) method (group 1) and a modified two-layer (University of Wisconsin solution/PFC) method (group 2) for 24, 48, 72, 96, and 120 hr (subgroups A, B, C, D, and E), the tissue concentration of ATP was determined using high-performance liquid chromatography, and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. Maintenance of normoglycemia for at least five days after transplantation was considered to indicate a viable pancreas graft. In group 1, functional success rates were A: 5/5, (100%), B: 4/4 (100%), C: 4/4, (100%), and D: 0/4 (0%), respectively. The ATP tissue concentrations were 7.47 +/- 0.47 (n = 5), 7.91 +/- 1.21 (n = 4), 8.29 +/- 0.21 (n = 4), and 4.94 +/- 1.11 (n = 4) mumol/g dry weight in groups 1A, 1B, 1C, and 1D, respectively. There was a statistically significant difference between viable groups (groups 1A, 1B, and 1C, 7.86 +/- 0.77 mumol/g dry weight [n = 13]) and the nonviable group (group D, 4.94 +/- 1.11 mumol/g dry weight (n = 4) (P less than 0.01). On the other hand, the functional success rates were 3/3 (100%), 3/3 (100%), 3/3 (100%), 5/7 (71%), and 0/3 (0%) in groups 2A, 2B, 2C, 2D, and 2E, respectively. Two of seven dogs died of causes related to the grafts (pancreatitis and thrombosis). The ATP tissue concentrations were 8.53 +/- 1.45 (n = 3), 9.64 +/- 1.77 (n = 3), 13.81 +/- 2.09 (n = 3), and 12.49 +/- 2.52 (n = 5) mumol/g dry weight in groups 2A, 2B, and 2C and in viable grafts in group 2D, respectively, but the ATP tissue concentration of nonviable grafts in group 2D and group E were 3.51 +/- 0.81 (n = 2) and 3.98 +/- 1.34 (n = 3) mumol/g dry weight, respectively. There was a statistically significant difference between viable groups (groups 2A, 2B, 2C and viable grafts in group 2D, 11.03 +/- 2.72 mumol/g dry weight [n = 14]) and nonviable groups (group E and nonviable grafts in group 2D, 3.79 +/- 1.06 mumol/g dry weight [n = 5]) (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Correlation between high adenosine triphosphate tissue concentration and good posttransplant outcome for the canine pancreas graft after preservation by the two-layer cold storage method. 175 85

In this study, changes of hepatic cellular ATP, ADP, and AMP, concentrations and mitochondrial oxidative phosphorylation were investigated in rats with experimental acute necrotizing pancreatitis (ANP). It was found that energy change (ATP + 1/2 ADP)/(ATP + ADP + AMP) of the liver decreased from 0.866 to 0.806 (P less than 0.05) 24 h after ANP, and to 0.769 (P less than 0.01) at 48 h. On the other hand, mitochondrial phosphorylative activity increased to 130% and 157% over the control at 12 h and 24 h respectively, and then rapidly dropped to 62% of normal value at 48 h. Blood ketone body ratio was positively correlated with hepatic energy charge level in ANP. The authors came to the following conclusions that: (1) In ANP, mitochondrial function damage resulted in decreased hepatic energy charge, which, in turn, led to hepatocellular impairment; (2) the measurement of blood ketone body ratio was a reliable indicator by which to assess the energy status of the liver in ANP.
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PMID:[Changes in hepatic energy metabolism in rats with acute necrotizing pancreatitis]. 208 1

Inpatient examinations included 17 patients with necrosis of the pancreas (4 patients had hemorrhagic and 14 fat necrosis): synthetic lymphocyte activity was studied by the luminescent method and the erythrocyte content of adenyl nucleotides by thin-layer chromatography in the toxic phase of pancreatitis. Synthetic lymphocyte activity was found to be decreased and the ATP pool of erythrocytes exhausted in the toxic phase of pancreatitis. Intravascular laser irradiation of the blood caused recovery of lymphocyte activity and increase in the ATP content in erythrocytes.
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PMID:[Effect of intravascular laser irradiation of the blood on blood cells in pancreatitis]. 277 Jan 94

In acute pancreatitis, damage to the liver is an important aspect of multiorgan failure. In 28 dogs (20 with bile-trypsin induced acute experimental pancreatitis (AEP], 'total' and 'free' activity of lysosomal hydrolases: beta-glucuronidase, cathepsins and acid phosphatase in mitochondrial and lysosomal subfraction of the liver were determined 12 h or 24 h after the induction of AEP. The respiratory control ratio with sodium succinate as a substrate, using Clarck's electrode and uncoupler-dependent ATP-ase activity in mitochondrial subfraction, was assayed. Groups of dogs were treated or pretreated with prostacyclin (PGI2), 20 ng.kg-1.min-1 i.v. for 12 or 13 h. The relative free activity of hydrolases was significantly elevated in untreated AEP after 12 h and was partially normalized in AEP after 24 h or after 12 h followed by treatment and pretreatment with PGI2. Respiratory control ratio was twice lower than normal in AEP after 12 h and partially normalized after 24 h post PGI2 treatment. The relative free activity of lysosomal hydrolases was highly negatively correlated with respiratory control ratio. It was concluded, that during AEP in dogs the function of liver mitochondria and lysosomal stability are impaired. The significant correlation found between the mitochondrial and lysosomal lesions points to lysosomal-mitochondrial interactions in liver damage in AEP. Prostacyclin in the investigated dose partially prevents the mitochondrial and lysosomal lesions in liver in this disease.
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PMID:Lysosomal-mitochondrial interrelationships in damage to the liver in acute experimental pancreatitis in dogs. Treatment with prostacyclin (PGI2). 304 48

Acute hemorrhagic pancreatitis (AHP) involves multiple organ failure probably caused by the toxic factor(s) released in pancreatitis-associated ascitic fluid (PAAF). We found that PAAF interferes with hepatic mitochondrial respiration resulting in severe disturbances in respiratory control (RCR) and ADP/O ratios. Pancreatitis was induced in dogs by retrograde pancreatic duct infusion and the resultant PAAF was centrifuged, filtered, and frozen until used. Two human PAAFs collected from AHP patients were treated in a similar manner. Rat liver mitochondrial oxygen uptake was measured at 30 degrees C before and after addition of ADP and PAAF. Paired control runs were made using pooled heat-inactivated dog serum. Tests with nine canine PAAFs showed a mean increase of 120% in state 4 respiration (P less than 0.0001). After exposure to PAAF, addition of ADP to previously coupled mitochondria did not induce state 3 respiration. The human PAAFs both showed significant increases in state 4 respiration (P less than 0.01) and a marked decrease in RCR. Dose-response tests with human and canine PAAFs showed a positive correlation between percentage increase in state 4 respiration and the concentration of PAAF used. These results confirm the presence in PAAF of mitotoxic substance(s) which cause irreversible mitochondrial damage. Inhibition of coupled mitochondrial respiration by PAAF with the resultant fall in ATP may be the causative agent for the tissue and organ damage observed in AHP.
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PMID:Mitochondrial dysfunction induced by pancreatitis-associated ascitic fluid. 684 50

Stimulation of the exocrine pancreas with cholecystokinin analogues leads to a variety of intraacinar processes, many coupled to energy consumption. It was hypothesized that extensive ATP depletion could play a role in the pathophysiology of acute pancreatitis, especially in the hyperstimulation (cerulein) model. Mice received seven intraperitoneal injections of cerulein at hourly intervals, at doses ranging from physiological (0.1 micrograms/kg) to pharmacological (50 micrograms/kg). A single dose of cerulein induced a 28-33% decrease in ATP, whereas a complete course of injections led to a nadir as low as 45% of the control value. The overall pattern of ATP tissue content during the observed time course was surprisingly similar in all four groups and statistically not different at any time point. Until 12 h, ATP levels in all groups remained below the control value. In contrast, serum amylase and light microscopy reflected a degree of pancreatitis in a close dose-response pattern to the administered cerulein dose. These findings suggest that ATP depletion--although probably facilitating acinar damage--does not seem to play a causal or primary role in the pathophysiology of acute pancreatitis.
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PMID:Energy metabolism in mouse pancreas in response to different dosages of a CCK analogue. 747 70

Studies in acutely inflamed pancreatic tissue in humans and animals suggest that premature activation of proteases within the gland plays a key role in its pathophysiology. The present study aimed to detect such protease activation in relation to protease inhibition and to changes in the concentrations of the vital cellular compounds ATP and glutathione in pancreatic tissue during caerulein-induced pancreatitis in rats. Within 1 h after supramaximal stimulation by intraperitoneal caerulein injection, pancreatic tissue activities of enzymatically active trypsin and elastase showed significant increases, accompanied by a twofold increase in trypsin inhibitory capacity. Over the same time course pancreatic ATP and glutathione concentrations dropped to 38% and 47%, respectively, after 1 h and reached a nadir of 22% and 28%, respectively, after 4-8 h. Intrapancreatic trypsin activation in this model, despite increasing trypsin inhibitory capacity, indicates concealed liberation of even more protease or enzyme-inhibitor complex instability. It is hypothesized that early acinar glutathione depletion, in part due to diminished ATP, could play a role in the premature activation of digestive enzymes by impairment of the integrity of the cytoskeleton and cell organelles or lowered defense capabilities against oxidant stress, finally leading to acute pancreatitis.
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PMID:Intrapancreatic zymogen activation and levels of ATP and glutathione during caerulein pancreatitis in rats. 753 55

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.
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PMID:Glutathione and ATP levels, subcellular distribution of enzymes, and permeability of duct system in rabbit pancreas following intravenous administration of alcohol and cerulein. 814 53

The purpose of this study was to evaluate the effect of free radical ablation therapy in acute hemorrhagic pancreatitis. Acute pancreatitis was induced in 64 rats by retrograde injection of 5% sodium taurocholate. Thirty animals were pretreated with 100,000 units/kg/hr of superoxide dismutase (SOD) and 400,000 units/kg catalase within the first 3 hr. After 0.5, 3.5, and 12 hr of observation time, serum enzymes and the tissue content of conjugated dienes, malondialdehyde, reduced and oxidized glutathione, as well as ATP, ADP and AMP were measured. In addition, tissue samples were examined by light microscopy. Untreated rats (N = 34) developed within 12 hr an acute hemorrhagic necrotizing pancreatitis with a concomitant increase in serum enzyme levels and a decrease in reduced glutathione and ATP. Within the 12-hr observation period, 57% of the animals died. Scavenger treatment improved the tissue damage and attenuated the increase of the serum enzyme levels and the decrease in reduced glutathione and ATP. Moreover, the lethality rate was significantly lower. Oxygen radicals seem to be instrumental for the development of acute hemorrhagic pancreatitis. Thereby, antioxidant treatment reduces tissue damage, biochemical alterations and extrapancreatic complications, thus improving the final outcome.
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PMID:Effect of antioxidant treatment in rats with acute hemorrhagic pancreatitis. 817 16


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