Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of a long-acting somatostatin analog (SMS 201-995) were studied in an established model of acute necrotizing pancreatitis in rats. SMS 201-995, when given prior to induction of pancreatitis, decreased the mortality rate from 100% to 40% (P = 0.0001). When treatment was given after induction of pancreatitis, the mortality rate was 75% (P = 0.2). Administration of SMS 201-995 did not influence the serum concentrations of amylase markedly, but the lipase levels were significantly lowered (P less than 0.05). The low levels of serum insulin and the glucose level in whole blood were not influenced. The volume of ascitic fluid was reduced (P less than 0.01). Moreover, less peritoneal fat necrosis was seen, suggesting a reduction in toxic factors in the ascitic fluid. Treatment with SMS 201-995 prior to induction of pancreatitis caused a significant increase in the levels of circulating 6-keto-PGF1 alpha, the stable metabolite of prostaglandin I2 (P less than 0.01). The levels of thromboxane B2 and prostaglandin E2 did not change significantly. The present data support the hypothesis that SMS 201-995 is an activator of prostaglandin I2, thereby modifying the course of the disease.
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PMID:Effects of long-acting somatostatin analog (SMS 201-995) on eicosanoid synthesis and survival in rats with acute necrotizing pancreatitis. 138 Apr 26

Prostacyclin metabolism in rat acute pancreatitis was evaluated by measuring the tissue levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and the urinary excretion of 2, 3-dinor 6-keto-PGF1 alpha. Acute pancreatitis was induced by i.v. cerulein perfusion and was confirmed by the pancreas enzyme changes and the histological findings. Significantly enhanced tissue and urinary prostacyclin levels were found in acute pancreatitis rats, when compared to the controls. Concomitantly, an enhanced tissue phospholipase A2 (PLA2) activity was also found. These data show the importance of 2, 3-dinor PGF1 alpha as an inflammatory marker in cerulein-induced pancreatitis.
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PMID:Altered systemic and tissue prostacyclin in cerulein induced acute pancreatitis in rats. 138 68

Severe necrotizing pancreatitis is accompanied by release of hemorrhagic ascites fluid (HAF), which is thought to be related to the occurrence and frequency of cardiocirculatory and pulmonary failure as a consequence of acute pancreatitis. The purpose of this study was to evaluate the role of HAF due to these systemic complications. Experiments were performed in 25 pigs (mean b.wt. 22 +/- 1 kg) under general anesthesia and mechanical ventilation. The animals received 50 ml/kg b.wt. i.p. of either physiologic saline solution (control CO, n = 9) or hemorrhagic ascites fluid (HAF, n = 16). HAF was obtained from 16 pigs with pancreatitis induced by intraductal infusion of bile salt. Eight animals in the HAF group were pretreated with indomethacin (10 mg/kg i.v. INDO/HAF). All animals were followed up for 6 h. Mean arterial pressure, cardiac output, and stroke volume fell significantly in the HAF (-25%, -27%, -27%) and in the INDO/HAF groups (-24%, -20%, -17%) as compared with controls (-6%, -6%, -6%). Also, left ventricular end-diastolic pressure (LVEDP) decreased by 52% and 48% in both HAF recipient groups, whereas LVEDP was unchanged in the control group. Myocardial contractility (Vmax) remained unaltered in all experimental groups. No significant differences in gas exchange and lung dry/wet weight ratio were observed. Lipase and PGI2 of the unpretreated HAF group rised to 203% and 198% in arterial blood at 6 h compared with unaltered levels in the control group. No increase of prostanoid concentrations was detected in the indomethacin-pretreated group, whereas lipase increase by a comparable extent as in the HAF group. We conclude that the early consequences of HAF are mainly characterized by systemic hypotension due to hypovolemia.
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PMID:Hemodynamic effects following intraperitoneal infusion of pancreatic ascites fluid. 141 Aug 1

Plasma thromboxane concentrations were found to be significantly elevated in acute necrotizing pancreatitis in rats, whereas prostaglandin I2 levels were not. The significance of these alterations was investigated. Pancreatitis was induced by injecting 5% sodium taurocholate into the pancreatic duct. Iloprost (ZK 36374, a stable analog of prostaglandin I2, 25 ng/kg body weight) decreased the mortality rate from 100% to 50%. When treatment with iloprost was combined with simultaneous administration of either Sibelium (flunarizine R 14,950, 0.2 mg/kg body weight) or dazmegrel (UK 38,485, 50 mg/kg body weight) an additional decrease in the mortality rate was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and flunarizine (a calcium entry blocker) also inhibits the effects of elevated thromboxane A2 levels. With flunarizine and iloprost the mortality rate was 40% (P less than 0.05); with dazmegrel and iloprost it was 10% (P less than 0.01). The results of the present study suggest that thromboxane A2 and prostaglandin I2 play a role in the course of acute necrotizing pancreatitis.
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PMID:Significance of thromboxane A2 and prostaglandin I2 in acute necrotizing pancreatitis in rats. 169 36

An experimental model of edematous pancreatitis in pigs was established and measurement of pancreatic macro- and microcirculatory parameters and determinations of pancreatic enzymes (lipase, phospholipase A) and vasoactive mediators (prostanoids, kallikrein, kininogen) were performed. During general anesthesia the pancreas was isolated in situ. Pancreatic microcirculatory parameters were measured using videofluorescence microscopy after iv administration of FITC-Dextran. In hourly collected samples lipase and phospholipase A activities were determined enzymatically, concentrations of kallikrein, kininogen, and selected prostanoids were measured by radioimmunoassay. Two experimental groups were studied: (1) control (n = 9); (2) edematous pancreatitis induced by injection of oleic acid into the pancreatic artery (free fatty acid, ffa; n = 10). The animals were followed up for 6 hr. Systemic hemodynamic parameters remained constant in both groups. In the pancreatitis group pancreatic blood flow and O2-consumption decreased significantly (-55 and -49%), while pancreatic vascular resistance increased significantly (+50%). During baseline conditions 41% of all capillaries were perfused. In the pancreatitis group there were both areas with persistent stasis as well as areas with continuous perfusion. However, in the latter areas the portion of perfused capillaries decreased significantly to 27%. In the control group the portion of perfused capillaries remained constant. Liberation of lipase and phospholipase A especially into lymph and ascites fluid was measured during pancreatitis. Furthermore, considerable releases of kallikrein into lymph (+50%) and ascites (+800%) and a marked consumption of kininogen in lymph (+90%) and in ascites fluid (+80%) were measured. Activation of the arachidonic acid cascade and a significant release of prostacyclin and thromboxane A2 into pancreatic venous blood and lymph was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oleic acid induced pancreatitis in pigs. 199 Feb 28

The mechanism of the liver damage in acute pancreatitis remains unsolved. The aim of this study was to evaluate RNA and DNA changes in the liver in Na-taurocholate pancreatitis in rats, with consideration being given to the protective effect of prostacyclin (20 micrograms.kg.24 h intraperitoneally). Total RNA increased both in treated and untreated rats after 24 hrs and even more after 48 hrs. After 48 hrs this increase was 35% higher in treated than in untreated rats. The RNA/DNA ratio paralleled the increase of total RNA. In 24 hrs incorporation of 3H-uridine into RNA increased 145% in untreated, and in 48 hrs 50% in treated rats. After 7 days 60% of treated animals survived as compared with 20% in the untreated group. The evident changes in RNA content, RNA/DNA ratio and RNA synthesis suggest a role for nucleic acid disturbances in the liver injury in acute pancreatitis. The beneficial effect of prostacyclin might, in part, be dependent on its effect on nucleic acid metabolism.
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PMID:The time course of liver DNA and RNA alterations in acute experimental pancreatitis in rats--a possible mechanism of prostacyclin (PGI2) protection. 247 34

Local variations of prostaglandin (PG) I2 and F2 alpha were studied in the pancreatic tissue during the first hour of an acute experimental necrohemorrhagic pancreatitis. The local pancreatitis was induced by trypsin injection into the interstitium of the splenic part of rat pancreas, and a saline injection was given into the interstitium in the duodenal part of the same pancreas as control. PGF2 alpha level was measured by specific radioimmunoassay (RIA), and the stable degradation product of PGI2, the 6-keto-PGF1 alpha, was determined also by RIA as an index of PGI2 level. The results were compared between the two regions and with control intact pancreata. The PGI2 level transiently decreased, whereas the PGF2 alpha increased in the region of localized hemorrhagic pancreatitis when compared with the intact pancreata. By contrast, the quickly disappearing edematous reaction induced by saline injection was accompanied by opposite changes in the two PGs studied: PGI2 was transiently elevated and PGF2 alpha diminished. In consequence, the ratio of the two PGs was shifted in favor of PGI2 in a transient edematous reaction and in favor of PGF2 alpha in hemorrhagic pancreatitis. It was concluded that PGI2 plays some protective role while PGF2 alpha might be one of the aggressive mediators in the inflammatory process. Their biological importance must be limited since PGF2 alpha alone did not induce pancreatitis nor did PGI2 protect against the trypsin-induced local pancreatitis.
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PMID:Prostaglandin F2 alpha and prostacyclin tissue levels in early phases of trypsin-induced acute pancreatitis in rats. 266 Jan 32

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

In an investigation of the pathogenesis of acute necrotizing pancreatitis (ANP) the plasma levels of TXB2, 6-keto-PGF1 alpha, and PGE2 were measured in rats. After induction of ANP by injection of 5% sodium taurocholate into the pancreatic duct, a marked increase in TXB2 levels and a slight increase in 6-keto-PGF 1 alpha levels were found. PGE2 levels decreased. Mortality was 100% within 30 h. Pretreatment with chloroquine, a phospholipase A2 inhibitor, led to a inhibition of TXB2 production, whereas 6-keto-PGF1 alpha and PGE2 levels showed a surprising slight elevation in the first 6 h. Pretreatment with chloroquine decreased mortality by 30%. Pretreatment with FPL 55712, a leukotriene synthesis blocker, caused an increase in TXB2 and PGE2 levels, whereas the formation of 6-keto-PGF1 alpha remained unaltered. Two out of nine animals survived after pretreatment with FPL 55712. The results of the present study indicate that arachidonate end products are involved in ANP. The significance of the high TXB2 levels, decreased PGE2 levels, and only slightly elevated 6-keto-PGF1 alpha levels during ANP requires further investigation. The thromboxane A2 to prostacyclin ratio may be important.
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PMID:Prostanoid imbalance in experimental acute necrotizing pancreatitis in rats. 316 72

The liver affection in acute experimental pancreatitis (AEP) could be reflected by changes of enzymatic activity in the liver and in serum. The histoenzymatic studies of the liver of dogs with AEP of different severity and time of duration induced according to Elliott's method were performed and the constellation of serum enzymatic activities considering treatment with prostacyclin was estimated. The histoenzymatic reactions on succinic dehydrogenase, lactic dehydrogenase and alkaline phosphatase were depressed with progression of time and severity of AEP. In contrast, the reaction on acid phosphatase was augmented at the same time. Serum AspAT, AlAT and alkaline phosphatase were augmented in the later phase of AEP, but acid phosphatase and beta-glucuronidase were not significantly changed. The treatment with PGI2 limited both histoenzymatic reactions and alterations of serum enzymatic activities. These results support the significance of changes in enzymatic activities in the course of liver reaction on pancreatogenic noxa during acute pancreatitis, and suggest the protective effect of PGI2 against liver injury in this disease.
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PMID:The enzymatic studies of the liver in acute experimental pancreatitis in dogs treated with prostacyclin (PGI2). 329 21


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