Endogenous hypertriglyceridemia intensifies the course of cerulein-induced pancreatitis in rat: relation with changes in the VLDL composition.

AIMS: To study if the course of cerulein-induced pancreatitis in rats changes in a state of triglyceride-rich lipoprotein metabolism alteration. METHODS: Two groups of rats received control diet during a 90-day period (A) and sucrose-rich diet to induce endogenous hypertriglyceridemia (B). Subgroups A2 and B2 received i.p. 45 microg cerulein/kg body weight (to induce acute pancreatitis). Histological examination of pancreas tissue, serum pancreatic lipase, lipoprotein profile and VLDL chemical composition were assessed. Then, pancreatic lipase hydrolytic activity on VLDL-triglycerides was evaluated in vitro. RESULTS: Cellular vacuolization was observed in all of the cerulein-injected rats, but only in subgroup B2 fat necrosis was present. Serum triglycerides were higher in subgroup B1 than in subgroup A1 (mean +/- SEM, mg/dl 123,77 +/- 25.7 vs. 65.8 +/- 7, p < 0.01). Triglycerides from rats fed with sucrose-rich diet, decreased after cerulein-induced pancreatitis (80.38 +/- 11.3 vs. 123,77 +/- 25.7, p < 0.02). Moreover, the endogenous hypertriglyceridemic rats showed an increment of VLDL triglyceride content, which decreased when rats were injected with cerulein. A negative correlation was found between VLDL-triglyceride content and serum pancreatic lipase activity (r = 0.58, p < 0.02). The in vitro assay showed a decrease in VLDL-triglyceride content post incubation with pancreatic lipase enriched serum (mean +/- SD: 59.2 +/- 27.7%, p < 0.01). CONCLUSIONS: The endogenous hypertriglyceridemia intensifies the course of cerulein-induced pancreatitis and it could be related to the decrease in VLDL-triglycerides as a consequence of pancreatic lipase hydrolytic activity.

[Cerulein-induced acute pancreatitis enhanced by chronic hyperlipidic diet in the rat]. / La dieta hiperlipídica crónica intensifica la pancreatitis aguda inducida por ceruleina en la rata.

The object of the present work was to study the relationship between acute pancreatitis (PA) and hyperlipidic diets. PA was induced by Caerulein (CE) by a single intraperitoneal doses (50 mcg/kg), after feeding the rats during 6 weeks with an hyperlipidic diet (45%). Rats with a normolipidic diet (lipids 5%) were used as control. The increase of serum lipase was similar in both groups treated with CE (control and with hyperlipidic diet). There were increase of interstitial edema, cariorrexis and a specially marked increase in the level of vacuolization of acinar cells with respect to the control group. It was concluded that chronic hyperlipidic diet increases histopathologic lesions in PA induced by CE in rats.

La dieta hiperlipidica cronica intensifica la pancreatitis aguda inducida por ceruleina en la rata / Cerulein-induced acute pancreatitis enhanced by chronic hyperlipidic diet in the rat

El modelo experimental de pancreatitis aguda (PA) inducido por ceruleína (CR) está caracterizado por un significativo aumento de la lipasa sérica, edema inersticial pancreático, observación poco frecuente de cariorrexis y aparición de vacuolas acinares. Ratas Wistar macho adultas fueron alimentadas por una dieta hiperlipídica (lípidos al 45 por ciento) durante 6 semanas, usando como control ratas con dieta normolipídica (lipidos 5 por ciento). Se indujo una PA mediante una dosis única de CR intraperitoneal de 50 mugr/Kg. El incremento de la lipasa sérica fue similar en ambos grupos tratados con CR (dieta control e hiperlipídica). Por otra parte se comprobó incremento del edema intersticial, de la cariorrexis y fundamentalmente del grado de vacuolización de las células acinares con respecto al grupo control. Se concluye que la dieta hiperlipídica administrada en forma crónica intensifica las lesiones histopatológicas de la PA inducida por CR.

La dieta hiperlipidica cronica intensifica la pancreatitis aguda inducida por ceruleina en la rata / Cerulein-induced acute pancreatitis enhanced by chronic hyperlipidic diet in the rat

El modelo experimental de pancreatitis aguda (PA) inducido por ceruleína (CR) está caracterizado por un significativo aumento de la lipasa sérica, edema inersticial pancreático, observación poco frecuente de cariorrexis y aparición de vacuolas acinares. Ratas Wistar macho adultas fueron alimentadas por una dieta hiperlipídica (lípidos al 45 por ciento) durante 6 semanas, usando como control ratas con dieta normolipídica (lipidos 5 por ciento). Se indujo una PA mediante una dosis única de CR intraperitoneal de 50 mugr/Kg. El incremento de la lipasa sérica fue similar en ambos grupos tratados con CR (dieta control e hiperlipídica). Por otra parte se comprobó incremento del edema intersticial, de la cariorrexis y fundamentalmente del grado de vacuolización de las células acinares con respecto al grupo control. Se concluye que la dieta hiperlipídica administrada en forma crónica intensifica las lesiones histopatológicas de la PA inducida por CR. (AU)

Effect of ethanol intake on pancreatic exocrine secretion in mice.

Swiss mice were fed conventional lab chow and 10% ethanol or water as drinking fluid for 2 weeks. Pancreatic juice was obtained by cannulation of the bile pancreatic common duct of mice anesthetized with urethane. Isolated pancreatic lobules were also obtained. The flow rate and the amylase output were determined in pure pancreatic juice. The release of amylase was measured in pancreatic lobule preparations. The basal pancreatic juice flow rate and the amylase output were significantly increased by ethanol consumption. The magnitude of the pancreatic juice flow rate and the amylase output responses to increasing doses of bethanechol, a cholinergic agent, was significantly decreased in ethanol-fed mice. The amount of spontaneously released amylase was higher in pancreatic lobule preparations from ethanol-fed animals than that from control mice, and the difference was abolished by addition of atropine to the incubation media. The amylase release rate in response to increasing doses of bethanechol was significantly reduced in lobule preparations from the ethanol-fed group. These data indicate that ethanol intake in mice has a stimulating effect on the spontaneous pancreatic secretion and lends support to the hypothesis that ethanol consumption increases the intrapancreatic cholinergic tone.

Effects of intravenous ethanol on basal bile-pancreatic secretion in nonalcoholic and alcohol-fed rats.

In nonalcoholic (NA) and alcohol-fed rats (AF), intravenous-ethanol-induced percentage changes in bile-pancreatic-secretion (BPS) were evaluated, with and without gastric juice diversion (GJD) and with and without BPS duodenal recirculation (DR). Even with GJD, ethanol elicited a slight increase in BPS. These changes were greater in AF animals even when performed without GJD. When intravenous ethanol was given under conditions of GJD and DR, there were marked differences between the NA and AF animals in the ethanol-elicited post-plateau percentage changes of BPS. NA animals evidenced no significant difference from controls. But in the AF rats, ethanol triggered a marked and significant increase of flow, protein concentration, and output that became progressively greater in successive collection periods. It is postulated that without DR, and the resulting lack of negative duodeno-pancreatic reflexes (DPR), there occurs a change in reactivity to intravenous ethanol of the hypothalamic-bulbar nuclei (HBN) and in the mechanisms that modulate the flow of cholinergic impulses through the intrapancreatic ganglia (IPG). The postulated consequence is predominance (slight in NA rats receiving intravenous ethanol, greater in AF rats) in discharge of positive impulses from HBN and flowing unimpeded through the IPG to the "pancreon" units. In the NA animal with DR, ethanol may enhance BPS values, but in the AF rats, impairment of the negative DPR elicited by chronic alcohol intoxication might, after an acute intravenous ethanol injection, favor the discharge of positive impulses from the HBN flowing unimpeded through the IPG. In the AF rats also, ethanol would activate the nonnicotinic receptors of the neurons of the "antral," "duodenal," and "celiac" autonomic brains.(ABSTRACT TRUNCATED AT 250 WORDS)

Pure pancreatic juice in humans: orange-lemon-juice-induced secretory effects. Comparative analysis with a regular meal, sorbitol, acidified peptone broth and secretin.

The secretory effect elicited by the ingestion of 100 ml of orange-lemon juice (O.-L.J.) was studied on pure pancreatic juice obtained from a catheter placed in the human Wirsung duct at surgery. These changes were compared with those evoked by a regular meal (R.M.), the ingestion of a Sorbitol solution (S.S.), the intragastric infusion of an acidified peptone broth (A.P.B.) and an i.v. single injection of secretin (Boots, 1.0 U/kg). The O.-L.J. induced purer pancreatic secretion response (flow, bicarbonate and enzyme output) than that triggered by the R.M., S.S. and A.P.B. The O.-L.J. evoked peak values, were observed earlier (60 min) than with a R.M. (90 min) ingestion. The 120-min-cumulative values confirmed these findings and disclosed that O.-L.J. elicits a rate of secretion and bicarbonate output closely similar to that of an i.v. secretin injection and amylase response greater than that evoked by this hormone. Thus, O.-L.J. ingestion proved to be an unexpected powerful stimulus of exocrine pancreatic secretion.

[Post-sectional antral peptic ulcer and antrofundic re-anastomosis in rats (manifestation of a probable antrofundic neuroendocrine center)]. / Ulcera péptica antral postsección y reanastomosis antrofúndica en la rata (puesta de manifiesto de un probable centro neuroendócrino antrofúndico).

The antrum-fundic section and re-anastomosis (AESR), liberates, in Wistar male rats, genuine antral peptic ulcers. They start within 20 days. They are progressive evolution, penetrating into all gastric walls. Between 7 and 8 months, they involve near organs (spleen, liver, pancreas) and produce a great inflammatory reaction of the peripancreatic ganglions. The antral peptic ulcer is induced if the gastric lesser curvature's nerves are sectioned and a concomitant pyloroplasty is done or not. The gastric hemisection, if anterior or posterior, break out the peptic ulcer only on the same side of the antrum-fundic interruption. In all this situations, except in cases of concomitant pyloroplasty, it is proved a pronounced and significantly increase of the gastric (g/kg), but not pancreatic index. In the AFSR series with nervous section on the lesser curvature and without pyloroplasty, the percentage of antral peptic ulcers in 56%. It is postulated the probably existence, at an antrum-fundic level, of a neuroendocrine center. Its nullification or disturbance by the section and re-anastomosis procedure could generate the antral ulcer and other histologic changes (increase of the "G" cells, hyperplasia of the parietal, ECL and "A like" cells) by one or various hypothetical ways: 1. Direct action, nullifying the normal blocking function of somatostative over the "G" cells and or parietal cells. 2. Disturbing or nullifying the motor pump effect of the gastric antrum, and on this way, enhancing the duodenum-gastric reflux with all know deleterious effects of the bile in the antrum particularly in an acid milieu. 3. Modifying, in the opposite direction, the sensitivity by one hand, of the "G" cells mass and by the other one, of the parietal, ECL and "A like" cells. The depression of the fundic sensitivity will induce the hyperplasia of the "G" cells, the hypersecretion of gastrin and, "a posteriori", all the secretory effects and trophic characteristic of it. 4. Disturbing the prostaglandins secretion, perhaps through a deficit of the nervous innervation, with the resulting epiphenomenon of a cytoprotection deficit mediated through the mucus and bicarbonate production. It is probably that the proposed physiopathogenic mechanism are associated and that the final result, the antral peptic ulcer is the consequence of an increase of the aggressive factors (acid, bile) and a concomitant depression of the defensive factors (cytoprotection), starting normally by the prostaglandins through the mucus and bicarbonate secretion.

Ulcera péptica antral postsección y reanastomosis antrofúndica en la rata (puesta de manifiesto de un probable centro neuroendócrino antrofúndico). / [Post-sectional antral peptic ulcer and antrofundic re-anastomosis in rats (manifestation of a probable antrofundic neuroendocrine center)]

The antrum-fundic section and re-anastomosis (AESR), liberates, in Wistar male rats, genuine antral peptic ulcers. They start within 20 days. They are progressive evolution, penetrating into all gastric walls. Between 7 and 8 months, they involve near organs (spleen, liver, pancreas) and produce a great inflammatory reaction of the peripancreatic ganglions. The antral peptic ulcer is induced if the gastric lesser curvatures nerves are sectioned and a concomitant pyloroplasty is done or not. The gastric hemisection, if anterior or posterior, break out the peptic ulcer only on the same side of the antrum-fundic interruption. In all this situations, except in cases of concomitant pyloroplasty, it is proved a pronounced and significantly increase of the gastric (g/kg), but not pancreatic index. In the AFSR series with nervous section on the lesser curvature and without pyloroplasty, the percentage of antral peptic ulcers in 56

. It is postulated the probably existence, at an antrum-fundic level, of a neuroendocrine center. Its nullification or disturbance by the section and re-anastomosis procedure could generate the antral ulcer and other histologic changes (increase of the [quot ]G[quot ] cells, hyperplasia of the parietal, ECL and [quot ]A like[quot ] cells) by one or various hypothetical ways: 1. Direct action, nullifying the normal blocking function of somatostative over the [quot ]G[quot ] cells and or parietal cells. 2. Disturbing or nullifying the motor pump effect of the gastric antrum, and on this way, enhancing the duodenum-gastric reflux with all know deleterious effects of the bile in the antrum particularly in an acid milieu. 3. Modifying, in the opposite direction, the sensitivity by one hand, of the [quot ]G[quot ] cells mass and by the other one, of the parietal, ECL and [quot ]A like[quot ] cells. The depression of the fundic sensitivity will induce the hyperplasia of the [quot ]G[quot ] cells, the hypersecretion of gastrin and, [quot ]a posteriori[quot ], all the secretory effects and trophic characteristic of it. 4. Disturbing the prostaglandins secretion, perhaps through a deficit of the nervous innervation, with the resulting epiphenomenon of a cytoprotection deficit mediated through the mucus and bicarbonate production. It is probably that the proposed physiopathogenic mechanism are associated and that the final result, the antral peptic ulcer is the consequence of an increase of the aggressive factors (acid, bile) and a concomitant depression of the defensive factors (cytoprotection), starting normally by the prostaglandins through the mucus and bicarbonate secretion.