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

The possible risk factors for failure of medical therapy were examined in 23 patients with pancreatic ascites or effusion. The ascites or effusion resolved completely in 10 patients after a mean (+/- SEM) of 30 +/- 2 days of conventional medical treatment. In five patients in whom conventional medical therapy failed, the addition of an octreotide (SMS 201-995) analogue to the medical therapy led to a resolution of the ascites (three patients) or effusion (two patients). Six patients underwent surgery after failed medical therapy, one patient died while receiving conservative therapy, and one patient refused hospital treatment. Serum sodium and albumin levels were significantly lower, and the ratio of total fluid protein to total serum protein was significantly higher in the group that failed to heal in response to conventional medical therapy. Nine of 11 patients with mild to moderately severe chronic pancreatitis healed in response to conservative therapy. Only one of 10 patients with advanced pancreatitis healed in response to conventional medical therapy. Our results suggest that a selective surgical approach is warranted to treat pancreatic ascites and effusion. In patients with mild or moderately severe pancreatitis, medical therapy is recommended. Patients with advanced pancreatic disease should be selected for early surgery. Octreotide may be useful in the patient in whom surgery may be associated with a prohibitive morbidity or mortality.
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PMID:Pancreatic ascites and effusion. Risk factors for failure of conservative therapy and the role of octreotide. 159 72

Despite the proposal that somatostatin or its stable analogue, octreotide (SMS-201,995), may exert an ameliorating effect on acute pancreatitis, data concerning its beneficial effect in this situation are conflicting. This study examines the effects of octreotide on acute pancreatitis, resulting from the retrograde injection of a bile salt (taurocholate) plus saturating trypsin into the common bile-pancreatic duct of the rat. Octreotide given before the induction of pancreatitis significantly reduced the levels of serum amylase and lipase, ascites amylase concentration, degree of leukocyte infiltration, and focal areas of pancreatic tissue necrosis. In contrast, administration of octreotide as soon as 5 min following induction had no demonstrable ameliorating effects on the pancreatitis. These results indicate that octreotide may have application to prophylaxis of acute pancreatitis in cases where bile salts may play a role in pathogenesis, but may not be beneficial in established acute pancreatitis.
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PMID:A somatostatin analogue is protective against retrograde bile salt-induced pancreatitis in the rat. 171 27

Because somatostatin is a potent inhibitor of pancreatic secretion, we hypothesized that pretreatment with somatostatin analogue octreotide (SMS 201-995) might prevent cerulein-induced edematous pancreatitis. We studied 18 rats prepared with jugular vein catheters. The following agents were administered intravenously to groups of four rats for 6 hours: 1 mL/h (control) crystalloid solution; 1-microgram/kg bolus then 1 microgram/kg per hour of octreotide; and 5 micrograms/kg per hour of cerulein; also, in a fourth group of six rats, octreotide and cerulein were administered simultaneously. At the end of experiments, blood was drawn for plasma amylase determinations; rats were killed and pancreata were examined. Supramaximal cerulein administration to conscious rats induced hyperamylasemia and edematous pancreatitis, confirming previous observations; in both groups of rats receiving cerulein, there was prominent interstitial edema, acinar vacuolization, and mild-to-moderate acute inflammation. While octreotide pretreatment of rats with cerulein-induced acute pancreatitis was associated with a lesser increase of wet pancreas weight and plasma amylase concentration, there was little overall benefit of octreotide pretreatment in this form of experimental acute pancreatitis.
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PMID:Does somatostatin analogue prevent experimental acute pancreatitis? 224 11

Somatostatin has been reported to promote closure of pancreatic fistulae, but use of the analog SMS 201-995 (Sandoz, Inc.) has not previously been published. We used this analog to treat two patients with end pancreatic fistulae refractory to conventional therapy. One patient had disruption of a pancreaticojejunostomy after pancreaticoduodenectomy and the other had acute necrotizing gallstone pancreatitis and disruption of the pancreatic duct in the tail. SMS 201-995 (100-150 micrograms/d) abruptly decreased fistula output by 50% in both patients but further increases in dosage had no further effect on output. Neither fistula healed after 3-4 wk of therapy. Treatment with somatostatin or its analogs alone will not lead to closure of a pancreatic fistula complicated by factors such as distal obstruction, infection, or foreign body. Somatostatin may promote closure of lateral fistulae and may simplify the management of patients with high output fistulae.
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PMID:Failure of somatostatin or an analog to promote closure of end pancreatic fistulae. 246 17

The effects of somatostatin (SRIF) and its long-acting analogue, SMS 201-995 on the prevention and treatment of acute pancreatitis were studied in rats. Acute pancreatitis was established by ligating the bile duct at the point of entry into the duodenum, thereby allowing reflux of bile into the pancreas. Administration of SRIF (4 micrograms kg-1 body wt IV followed by a 12 h infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC) at the time of bile duct ligation prevented the increase in the serum concentrations of amylase and lipase observed in control rats 12 h after bile duct ligation. Moreover, SRIF and SMS 201-995 administration prevented development of the histological changes consistent with acute pancreatitis observed in control animals. These results suggest that SRIF or SMS 201-995 may be of value in preventing acute pancreatitis following ERCP or after surgery on the pancreas. In rats with established pancreatitis, SRIF (IV bolus of 4 micrograms kg-1 body wt followed by a 24 h continuous infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC followed by a similar dose 12 h later): (1) significantly improved survival; (2) produced histological changes in the pancreas consistent with organization and healing; (3) prevented the accumulation of ascitic fluid; (4) reduced the serum levels of amylase and lipase. These results suggest that SRIF and SMS 201-995 may prove valuable in the treatment of established acute pancreatitis in man.
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PMID:Effects of somatostatin and a long-acting somatostatin analogue on the prevention and treatment of experimentally induced acute pancreatitis in the rat. 258 47

Natural Somatostatin has a short half-life (3 min), is only active after intravenous administration and causes a rebound hypersecretion of hormones after discontinuation of administration. Recently a long-acting powerful Somatostatin analog was developed (SMS 201-995; Sandostatin) which has a half-life of 113 min after subcutaneous administration. After administration of this analog no rebound hypersecretion of hormones was observed. In the present review the effects of the acute administration and of long-term treatment with SMS 201-995 in acromegalic patients is discussed. In addition the potential role of therapy with Somatostatin analogs and the preliminary effects of Somatostatin and/or SMS 201-995 are discussed in disorders of gastro-intestinal function (haemorrhages, diarrhoea, pancreatitis and endocrine pancreatic tumours), diabetes mellitus, central nervous system disturbances and oncology. Finally, several aspects of the tolerance, tachyphylaxis and side effects of SMS 201-995 are discussed.
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PMID:Non-pituitary actions of somatostatin. A review on the therapeutic role of SMS 201-995 (sandostatin). 287 90

Somatostatin is present in the gastrointestinal tract in appreciable amounts. The highest concentrations of the polypeptide are found in the stomach, the upper small intestine, and the pancreas. Within the gastrointestinal tract, somatostatin inhibits various functions, including endocrine and exocrine secretion, motility, blood flow, absorption, and growth. The polypeptide regulates these functions by endocrine, paracrine, neurocrine or luminal mechanisms. Abnormalities of endogenous somatostatin have been implicated in several gastrointestinal disorders, including the somatostatinoma syndrome, antroduodenal D-cell hyperplasia, peptic ulcer, obesity, and liver cirrhosis. Because of its potent inhibitory effects, somatostatin or somatostatin-analogues have been used as therapeutic agents in various clinical conditions, such as upper gastrointestinal haemorrhage, endocrine pancreatic tumours, gastrointestinal and pancreatic fistulas, pancreatitis, secretory diarrhoea, and dumping syndrome. The recent availability of the synthetic long-acting somatostatin-analogue SMS 201-995 (Sandostatin) has greatly facilitated the therapeutical application of somatostatin-polypeptides.
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PMID:Clinical and pathophysiological aspects of somatostatin and the gastrointestinal tract. 289 34

Brattle-Boro type rats with average weight of 200 gms were used for the experiment. We established 5 groups with 10 rats in each. Group I was the control group, Group II pancreatic trauma group and Group III rats were the pancreatitis group induced by 50% alcohol. Groups IV and V were the groups in which Octreotide was injected in different time intervals after induction of pancreatitis by 50% alcohol. Amylase values were statistically significant between the control group in which Octreotide was injected in different time intervals after induction of pancreatitis by 50% alcohol. The amylase values were statistically significant between the control group and the experiments (t2 = 4.69 p < 0.001, t3 = 8.06 p < 0.00001, t4 = 4.23 p < 0.002, t5 = 4.3 p < 0.002), and it was also significant between Group III and Groups II, IV, V (t2 = 9.62 p < 0.0001, t4 = 10.26 p < 0.0001, t5 = 3.69 p < 0.005), but it was not found significant between Groups II and IV, V (t4 = 0.52 p < 0.6, t5 = 1.69 p < 0.1). Histopathologic examination of the trauma group showed congestion, minimal lymphomonocyte infiltration. Patchy necrosis and shrinkage of the acinar cells with ductal dilatation were seen in the SMS 201-995 injection groups which were more pronounced in Group V. As a conclusion SMS 201-995 is not effective to prevent the ongoing pathology of pancreatitis but the increasing values of amylase were limited on the level of simply induced traumatic pancreatitis. It may be useful in the suppression of the enzymatic production during the course of pancreatitis.
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PMID:The effect of octreotide (SMS 201-995) on experimentally induced pancreatitis with 50% ethyl alcohol in rats. 752 26

The mechanism whereby somatostatin (SS) produces beneficial effects in established pancreatitis induced by pancreaticobiliary duct ligation (PBDL) is still not clear. The aim of the work was to evaluate the possibility of a direct action of SS on pancreatic acinar cells from rats with acute pancreatitis. For this purpose, we studied the SS-receptor-adenylate cyclase system in pancreatic acinar membranes from both, control rats and rats with experimentally induced acute pancreatitis. On the other hand, it has been reported that cholecystokinin (CCK) diminishes the number of SS receptors in pancreatic acinar cells. Proglumide, a CCK receptor antagonist reduces the severity of acute pancreatitis in the rat. Therefore, we have also examined the effect of proglumide on the somatostatinergic system in controls and rats with acute pancreatitis. Fourteen hours after PBDL, the SS receptors, the capacity of the SS analogue SMS 201-995 to inhibit forskolin-stimulated adenylate cyclase activity and PTX-catalyzed [32P] ADP-ribosylation of the alpha1 subunits of Gi proteins could not be detected in pancreatic acinar membranes. One month after reopening the closed pancreaticobiliary duct (PBD), the pancreas showed regeneration of acinar cells, and the above-mentioned parameters were significantly lower than in the control group. Two months after reopening the closed PBD, all these parameters had returned to control values. The administration of proglumide (20 mg/kg i.p.), a cholecystokinin receptor antagonist, accelerated pancreatic regeneration and approached all these parameters to control values one month after reopening the closed PBD. The present study suggests that the beneficial effects of SS on established pancreatitis induced by PBDL may not be due to a direct action of the peptide on pancreatic acinar cells at least at 14 hours after PBDL. In addition, these findings suggest that in established pancreatitis the effect of proglumide on the SS receptor-adenylate cyclase system could be due to its action on pancreatic regeneration.
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PMID:The somatostatin receptor-adenylate cyclase system in rat pancreatic acinar membranes after temporary pancreaticobiliary duct ligation. 940 49


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