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

CR 1409, a glutaramic acid derivative with competitive cholecystokinin-antagonistic activity, was administered IP and evaluated in comparison with proglumide (the model CCK-receptor antagonist), gabexate (protease inhibitor) and PGE2 (cytoprotective) on two different models of experimental pancreatitis. Acute pancreatitis was induced in mice by six IP injections of 50 micrograms/kg caerulein at hourly intervals. The drugs were administered 30 minutes before each caerulein administration. Blood samples and pancreata were collected 3 hours after the last caerulein injection. In the second experiment, pancreatitis was induced in rats by injecting 0.3 ml 6% sodium taurocholate interstitially into the pancreas. The drugs were administered twice, 30 minutes before and 3 hours after taurocholate. The animals were killed 6 hours after laparotomy and blood samples and pancreata were collected. CR 1409 exhibited on both pancreatitis models a protective effect in a dose range of 0.3-10 mg/kg. Proglumide exhibited a protective activity at higher doses (200-400 mg/kg). Gabexate and PGE2 were effective only in pancreatitis induced by taurocholate in a dose range of 30-60 mg/kg and 60-130 micrograms/kg respectively. These results, showing a high protective effect of CR 1409 on different models of acute pancreatitis, suggest an important role of CCK in the pathogenesis of pancreatitis.
 ...
PMID:Protective effect of CR 1409 (cholecystokinin antagonist) on experimental pancreatitis in rats and mice. 310 90

The usual consumption of calories, fat, protein, and carbohydrate, and the exocrine pancreatic function estimated in duodenal juice after an intravenous injection of secretin and cholecystokinin (CCK), have been studied with the same method and by the same team in Kerala (South India) and in Marseille (France) in apparently normal children (7 Indians, 21 French), in normal adults (23 Indians, 17 French), and in patients presenting with chronic calcifying pancreatitis (8 Indian children, 28 Indian adults, 25 French adults). Although they had a low protein intake (children controls: 32.1 +/- 14 g/day (SM), children pancreatitis: 51.1 +/- 15, adult controls: 51.3 +/- 4.9, adult pancreatitis: 55.7 +/- 5.7), the exocrine secretion of Indian controls was not very much modified in comparison with Europeans. Therefore, Indians are less affected by the insufficient diet than the population of Ivory Coast previously studied by the same group. The diet of Indian patients is characterized by a moderately low protein intake and a very low fat intake (18.5 g/day +/- 2.3 (SM) for children 23.4 g/day + 2.7 for adult patients). Comparison between different series of patients studied in different countries with the same method suggests that kwashiorkor or cassava consumption have no evident role in the etiology of chronic tropical pancreatitis. The possible role of a low fat diet is suggested and needs further exploration.
 ...
PMID:Diet, pancreatic function, and chronic pancreatitis in south India and France. 336 42

The phospholipid effect involves agonist-induced breakdown of phosphatidyl inositol (or polyinositides) generating second messengers followed by increased incorporation of 32P during the resynthetic phase of the cycle. Ethanol, an aetiological factor in pancreatitis, has been shown to have various effects on pancreatic secretion. In this study ethanol decreased the incorporation of 32P into phosphatidyl inositol but had no effect on the stimulated breakdown of prelabelled phosphatidyl inositol. However, in addition to recycling of phosphatidyl inositol stimulation of pancreatic tissue results in increased incorporation of precursors into other phospholipids. Cholecystokinin increased the incorporation of both [U-14C] glucose and 32P into phosphatidyl ethanolamine 3-fold but had no effect on 32P incorporation into phosphatidyl choline. As well as increased incorporation of 32P into phosphatidyl inositol (8-fold) cholecystokinin also increased the incorporation of [U-14C] glucose into phosphatidyl inositol (4-5-fold) implying significant de novo synthesis of 1,2 diacyl glycerol in addition to the currently accepted recycling of the 1,2 diacyl glycerol back to phosphatidyl inositol. Ethanol caused an inhibition of 32P incorporation into total phospholipid of rat pancreas during basal and stimulated conditions. When individual phospholipids were separated ethanol was found to decrease the incorporation of 32P into phosphatidyl choline under basal conditions and into all phospholipids during cholecystokinin stimulation. With [U-14C] glucose as the precursor, ethanol inhibited its incorporation into phosphatidyl choline only. Ethanol did not alter the total 32P radioactivity in the aqueous phase of the pancreatic extract nor the percent incorporated into nucleotides. This excluded decreased uptake of 32P and incorporation into nucleotides as a mechanism for the differential inhibition of 32P versus [U-14C] glucose incorporation into phospholipids other than phosphatidyl choline under stimulated conditions.
 ...
PMID:The effect of ethanol on phospholipid metabolism in rat pancreas. 337 97

Loxiglumide (D,L-4-(3,4-dichloro-benzoylamino)- 5-(N-3-methoxypropyl-pentylamino)-5-oxo-pentanoic acid, CR 1505) is a derivative of pentanoic acid and belongs to a newly discovered class of agents with cholecystokinin antagonistic activities. Loxiglumide has preventive effects on different types of experimental pancreatitis, induced e.g. by ceruletide (i.p. ED50 ca. 9 mumol/kg), by intrapancreatic taurocholate (i.p. ED50 ca. 80 mumol/kg) or by choline-deficient ethionine-supplemented diet (i.p. ED50 ca. 45 mumol/kg). Loxiglumide has a simple, non-polypeptidic chemical structure and may be a candidate for clinical investigations in man, e.g. for pancreatitis.
 ...
PMID:Loxiglumide protects against experimental pancreatitis. 343 90

Derivatives of 5-(dipentylamino)-5-oxo-pentanoic acid are a new class of non-peptide cholecystokinin (CCK) antagonists. The most potent compound, D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid (lorglumide, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent CCK antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini. In vivo lorglumide antagonizes the contraction of the gall bladder of the guinea pig and of the dog provoked by i.v. CCK-8 or ceruletide (caerulein). It antagonizes the satiety effect of CCK-8 in the rat and is protective against ceruletide-, taurocholate- and diet-induced pancreatitis. Lorglumide is therefore a useful pharmacological tool to study the functions of CCK. For its pharmacological properties, its relatively low toxicity and because it is active also after oral administration, lorglumide is a candidate for diagnostic or therapeutic use in man when an involvement of CCK is suspected.
 ...
PMID:Pharmacological properties of lorglumide as a member of a new class of cholecystokinin antagonists. 344 35

Motor disorders of the sphincter of Oddi (SO) may play a role in the pathogenesis of idiopathic recurrent pancreatitis. We have compared manometric records from the SO in 28 patients with idiopathic recurrent pancreatitis with those from 10 control subjects. Patients with idiopathic recurrent pancreatitis had presented with episodes of upper abdominal pain associated with abnormal serum levels of amylase on at least two occasions, in the absence of alcohol abuse and biliary disease. Retrograde pancreatography was either normal or showed only minor changes in pancreatic ducts. A triple lumen low compliance manometric system was used to obtain a 5 min recording of spontaneous SO motor activity. From this recording were determined the SO basal pressure, SO phasic contraction amplitude, SO wave frequency and direction of wave propagation. The SO response to intravenous cholecystokinin-octapeptide (CCK-OP) 20 ng/kg was then recorded for at least 3 min. Twenty-five of the twenty-eight patients demonstrated one or more manometric abnormality when compared with data from the ten controls. The most frequent abnormality was an elevated SO basal pressure in 16 patients. In addition, excess of retrograde contractions in nine patients, high frequency of SO phasic contractions in nine patients, absence of phasic contractions in three patients, and paradoxical response to CCK-OP administration in two patients were recorded. This study has demonstrated a spectrum of sphincter of Oddi manometric disorders in patients with idiopathic recurrent pancreatitis and suggests that motility disorders of the sphincter of Oddi may be associated with episodes of pancreatitis.
 ...
PMID:Sphincter of Oddi motility disorders in patients with idiopathic recurrent pancreatitis. 406 50

The influence of hormonal stimulation by caerulein administration on acute experimental pancreatitis was investigated in the rat. An experimental model of moderate acute pancreatitis was selected after injecting buffer solution containing sodium taurodeoxycholate and various concentrations of trypsin into the bile-pancreatic duct. During acute experimental pancreatitis caerulein administration increased the mortality rate, the incidence of ascites and the activity of amylase in ascites. Caerulein rendered the pancreatitis more severe also as judged from blind macroscopic evaluation. Amylase and insulin levels in serum and plasma were elevated 6 and 25 h after induction of pancreatitis irrespective of caerulein administration. In pancreatitic rats caerulein decreased the activities of digestive enzymes in pancreatic tissue. The results show that hormonal stimulation by the cholecystokinin-pancreozymin analogue caerulein during acute experimental pancreatitis is harmful.
 ...
PMID:Influence of hormonal stimulation by caerulein on acute experimental pancreatitis in the rat. 616 30

The influence of exogenous administration and endogenous release of certain g.i. hormones on the course of acute experimental pancreatitis was studied. Administration of 2 g of a pellet diet every eight hours decreased survival, as did repeated s.c. administration of the cholecystokinin-analogue caerulein. Also oral administration of a trypsin inhibitor--releasing intestinal factors or hormones stimulating pancreatic enzyme synthesis and secretion--decreased survival. On the other hand repeated s.c. administration of secretin or an anticholinergic drug (Pro-Banthine), or oral administration of 0.1 N HCl every eight hours did not influence survival. At blind macroscopic evaluation, caerulein was found to cause signs of more severe disease. All pancreatic rats had increased S-amylase levels, but there was no difference between any of the groups. In peritoneal fluid, however, caerulein caused an increase in the amylase activity. The results suggest that elevated S-levels of g.i. hormones, which primarily stimulate pancreatic enzyme synthesis and secretion, are harmful in acute experimental pancreatitis.
 ...
PMID:Influence of gastrointestinal hormones on the course of acute experimental pancreatitis. 618 81

Recent developments of manometric and endoscopic instrumentation have rekindled interest in sphincter of Oddi function. As a result of human and animal studies, our understanding of normal sphincter of Oddi physiology has increased and possible motility abnormalities are being identified. Manometric studies have shown that the sphincter of Oddi is characterized by prominent phasic contractions which are super-imposed on a low tonic pressure. The phasic contractions are orientated mainly in an antegrade direction; however, both simultaneous and retrograde contractions are registered. Cineradiography has demonstrated that the phasic contractions have a propulsive function, expelling small volumes of fluid from the common bile duct into the duodenum. Intravenously administered cholecystokinin-octapeptide normally inhibits the phasic contractions and reduces the sphincter tone. Motility abnormalities may occur if the sphincter of Oddi exhibits abnormally high tone, alteration in the direction of the phasic contractions, abnormal changes in the contraction frequency, or abnormal responses to hormonal stimulation. Preliminary human studies demonstrate disorders in sphincter of Oddi motility patterns, suggesting that motility abnormalities may be associated with choledocholithiasis, dyskinesia and idiopathic relapsing pancreatitis.
 ...
PMID:Sphincter of Oddi motility. 632

The presence of alpha 1-proteinase inhibitor (alpha 1-PI) in pure human pancreatic juice was demonstrated. Its concentration was measured using the radial immunodiffusion technique and compared to transferrin and albumin concentrations. In normal pancreatic juice the mean alpha 1-PI level (expressed in percent of total protein) was 0.21 +/- 0.02, whereas the mean levels of the two other serum proteins were 0.14 +/- 0.01 for transferrin and 0.90 +/- 0.07 for albumin. These levels increased significantly in the juice of patients with chronic calcifying pancreatitis. The serum origin of alpha 1-PI present in pancreatic juice was demonstrated by the good correlation existing between alpha 1-PI and albumin as well as between transferrin and albumin. In addition, in each case the alpha 1-PI level was found to be higher in secretin-stimulated juice than in cholecystokinin-stimulated juice. A similar pattern was also found for albumin.
 ...
PMID:Alpha 1-proteinase inhibitor in pure human pancreatic juice. 640 77


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