A comparative study of the effectiveness of regulatory peptides in acute experimental pancreatitis

The effect of regulatory peptides on the functional activity of pancreatic cells and phagocytic cells of reticuloendothelial system were determined in intact dogs against the background of acute experimental pancreatitis. Assessment of the efficacy of regulatory peptides was made with the aid of scintigraphic studies in gamma chamber using for this purpose colloid 198Au and 75Se-methionine. It was established that introduction of regulatory peptides to dogs leads to inhibition of capture of labeled methionine by pancreatocytes, practically not influencing the elimination of colloid gold from circulation.     

The effect of regulator peptides on pancreatic endocrine function in experimental acute pancreatitis

The comparative analysis of the influence on the glucose metabolism of rats in acute pancreatitis of synthetic analogues was made: somatostatin, calcitonin, leu-enkefalin-dalargin. It was shown that dalargin has the maximum normalizing effect as a result of its antistress qualities. Physiological reaction of beta-cells is preserved in infusion of somatostatin. However, infusion of calcitonin results in the distortion of counterregulatory action of insulin and glucagon.     

Xanthine oxidase activity in mouse pancreas: effects of caerulein-induced acute pancreatitis

The development of acute pancreatitis involves a number of pathophysiological changes which result in pancreatic tissue damage. Data from several models of acute pancreatitis suggest that the in vivo conversion of the enzyme xanthine dehydrogenase to xanthine oxidase may cause tissue damage by the subsequent generation of oxygen-derived free radical products. In the present studies, acute pancreatitis was induced in mice by the administration of supramaximal secretory doses of caerulein, a cholecystokinin analogue. Pancreatic xanthine oxidase activity was observed to occur in the dehydrogenase form in both control and treated mice. Artifactual conversion to the oxidase form could be induced by exclusion of 2-mercaptoethanol and phenylmethylsulfonyl fluoride from the buffer during tissue preparation. These data indicate that no significant conversion of xanthine dehydrogenase to oxidase is associated with this model of acute pancreatitis in mice.     

Effect of sodium thiosulfate on the pancreas in experimental pancreatitis]

Histological and histochemical study of the pancreas of albino rats and experimental pancreatitis showed the use of sodium thiosulfate to considerably inhibit the progress of necrotic changes and circulatory disturbance. The preparation prevented recidivation of pancreatitis and inhibited sclerotic changes in the gland. Sodium thiosulfate stimulated the regenerative process including regenerative hypertrophy and expressed epimorphosis.     

Pancreatic enzyme activity in early phases of acute experimental pancreatitis in rats

Experiments were performed on laboratory rats with acute pancreatitis caused by local freezing the pancreas with chlorethyl. An active action of enzymes alpha-amilase, lipase, phospholipase A2, was revealed. During the first hours, an increase in action of all three enzymes, particularly that of phospholipase A2, was found. It was established that the lipid spectrum of pancreas had changed. It shows that cell membranes were destroyed. Experiments revealed an activating role of Ca2+ ions for all the enzymes and a correcting action of chlorpromasine.     

Effects of experimental acute pancreatitis in dogs on metabolism of lung surfactant phosphatidylcholine

Acute haemorrhagic pancreatitis was produced in the dogs by transduodenal injection of autologous bile into the main pancreatic duct. There was no significant change in the activity of three regulatory enzymes of phosphatidylcholine biosynthesis (glycerophosphate acyltransferase, cytidyltransferase and cholinephosphotransferase) in lung; however, there was a 42% decrease in the amount of dipalmitoyl phosphatidylcholine (surfactant) in lung lavage due to acute pancreatitis. The decrease in lavage phospholipid content was associated with 5-fold increase in phospholipase A2 activity of lung lavage, and massive accumulation of osmiophilic spheroid structures in the alveolar space.     

Effect of sodium thiosulfate on viable areas of the pancreas in experimental pancreatitis

Experimental pancreatitis in white rats is marked by stromal edema, dystrophic changes of acinar cells, with intracellular edema in an intact part of the pancreas. Subsequently the acinar cells undergo intracellular regeneration and hypertrophy, which is accompanied by intensive incorporation of 14C-leucin into glandular proteins. Sodium thiosulfate prevents the development of stromal edema and intracellular edema of the acinar cells and retards the development of acinar cell hypertrophy. The drug produces an inhibitory action on 14C-leucin incorporation into pancreatic proteins.     

Effect of 5-fluorouracil on the enzymatic activity of the pancreas and blood serum of rats with acute pancreatitis

The effect of 5-fluorouracil on the activity of pancreatic enzymes was studied in rats with acute pancreatitis. 5-Fluorouracil was injected intraperitoneally in a dose of 4.5 mg per 100 g body weight. Pancreatic transaminidase as well as serum alpha-amylase and trypsin levels decreased starting from 3--6h after the induction of acute pancreatitis. 5-Fluorouracil inhibited RNA and DNA synthesis and blocked the synthesis of pancreatic enzymes.     

Features of the morphofunctional state of the endocrine part of the pancreas during the development of experimental diabetes in the presence of regulatory peptides

The multiple 7-day intranasal introduction of PGArg and GPArg peptides at a dose of 1 mg per kg body weight before the injection of the diabetogenic dose of alloxan provided the maintenance of normoglycemia in rats. The similar introduction of PGPArg peptide did not provide any protection against the development of diabetes mellitus. The quantity of pancreatic islets in the animals from this group remained quite comparable to the norm, but the total number of cells per islet was below the norm, as well as in the control group. The GPArg peptide showed the best results as a preventive anti-diabetic agent.     

Effects of regulatory peptides on the porcine lower oesophageal sphincter

Studies were performed to investigate the effects of neurotransmitters and neurotransmitter candidates (substance P, VIP, somatostatin, Met-enkephalin, gastrin-17, CCK-4 and -8, neurotensin and TRH) of the newly discovered peptidergic nervous system on lower oesophageal sphincter pressure in anaesthetized pigs. All neuropeptides were infused over 2 min periods in 6 different doses, separated by resting periods of at least 1 min, directly into the arterial supply of the lower oesophageal sphincter. Substance P caused a dose-dependent increase in lower oesophageal shpincter pressure; the threshold dose was 9 pmol . kg-1 . min-1 and half maximal response occurred at 72 pmol . kg-1 . min-1. None of the other polypeptides, however, influenced the resting lower oesophageal sphincter. These studies show that substance P is a potent stimulant of smooth muscle in the lower oesophageal sphincter, suggesting that this peptide may be an important regulator of lower oesophageal sphincter pressure.     

Pathobiology of experimental acute pancreatitis.

Pancreatic duct obstruction, even in the absence of biliary obstruction and/or bile reflux into the pancreatic duct, can trigger acute hemorrhagic necrotizing pancreatitis. The earliest changes are seen within acinar cells. Early derangements in acinar cell biology include inhibition of digestive enzyme secretion and the co-localization of lysosomal hydrolases with digestive enzyme zymogens. Under appropriate conditions, this co-localization could lead to digestive enzyme activation within acinar cells.     

Effect of synthetic analogs of L-enkephalin on viable areas of the pancreas in experimental pancreatitis

Synthetic analogues of L-enkephalin--tageflar and dalargin were studied for the treatment of experimentally-induced pancreatitis of rats. It was concluded that morphometric features of an intact part of the pancreas were not significantly changed with the use of tageflar. The intensity of 14C-leucine inclusion in the proteins of an intact part of the pancreas was strongly suppressed and the cytoplasm of exocrine pancreocytes was overloaded with zymogen granules. With the use of dalargin, a moderate hypertrophy of exocrine pancreocytes and intensification of 14C-leucine inclusion developed gradually. The number and disposition of zymogen granules were not significantly changed, as compared to acute pancreatitis. Both drugs disturbed the process of acinar reconstruction into tubular complexes in the marginal areas.     

A way of functional classification of regulatory peptides. Parameters of divergent and convergent evolution of regulatory peptides

A mathematical method has been presented for systematization of functions of regulatory peptides (RP) and evaluation of directions of evolutionary development of RP systems. For this purpose, traditional methods of vector algebra and multi-dimensional space were used. Effects of various peptide regulators on anxiety, depression, and memory are considered by the example of the three-dimensional space. A way of the functional classification of peptides has been proposed.     

The effect of 5-fluorouracil on experimental acute pancreatitis

The present study was undertaken to elucidate the effects of different doses of 5-fluorouracil on experimental acute pancreatitis. Twelve mongrel dogs were used. Acute pancreatitis was induced by intraductal injection of sunflower-oil. Two groups of animals were treated with intravenous 5-fluorouracil: 1 mg/kg body weight for the first group of 5 animals, and 5 mg/kg body weight for the second one of 7 animals in subsequent three postoperative days. All the animals in the first group died within 24 to 36 hours due to acute haemorrhagic pancreatitis. All the animals in the second one survived longer than 36 hours. A statistically significant increase of serum amylase and lipase levels was found in pancreatitis with significant decrease of them during treatment. Three to 8 weeks later signs of chronic pancreatitis could be detected in surviving dogs.