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In this work we have demonstrated the influence of a short chain fatty acid (acetate) on the number of enterochromaffin (EC) cells containing serotonin (5HT), at two different pH (pH 6.9 absorptive stimuli, and pH 2.9 secretory stimuli), infused into the colon during one hour. The number of EC cells decrease significatively, specially in the cecum with a solution of low pH (2.9). The action of piprenzepine in preventing this reduction demonstrated that was partly mediated by a cholinergic receptor mechanism. On the other hand, a decrease on the release of 5HT to the lumen was a observed under the influence of pirenzepine. We conclude that the short chain fatty acid acetate, at a low pH induces the release of serotonin through a cholinergic mechanisms indicated by the inhibition observed with antimuscarinic drug.

The stimulating effect of cisapride on the motility of the digestive tract is well known. However, there are only a few studies on the influence of this drug on the absorptive or secretory activity of the colonic mucosa. In the present study, the ability of cisapride to alter the mural transport of water and electrolytes in the colon and its effects on mucus secretion and albumin permeation were studied. The effects of cisapride on the rat colon in vivo were studied under different conditions, by means of an instillation of sodium acetate solution at pH 6.9, which induced absorption of water and electrolytes, and in two models of colonic secretion, one employing the instillation of an acetic acid solution at pH 2.9 and the other, an intravenous infusion of 5-hydroxytryptamine (serotonin) 45 micrograms.kg-1.min-1 together with intracolonic instillation of sodium acetate. Cisapride (i.v.), at a dose of 0.32 mg.kg-1, in rats whose colon was instilled with sodium acetate (pH 6.9) induced an increase in sodium absorption and a reduction in water absorption. Cisapride (i.v.), at doses of 0.32, 0.64 and 1.0 mg.kg-1, inhibited the secretion of water, Na+, Cl-, and mucus and the permeation of albumin induced by acetic acid instillation or by serotonin infusion. It is concluded that the effect of cisapride on the colonic mucosa varies in accordance with the functional mucosal conditions and that this action may be of clinical importance.

Depending on quantity and/or quality, the presence of lactic acid in the colonic lumen may be associated with metabolic damage of the colon. The influence exerted on the rat colon by the different isomers and racemic of the lactic acid, used at two extreme dilutions (20 and 100 mEq/l), has been the subject of study in this paper. The modifications on pH, water and electrolytes are associated with the absorptive/secretory action of the colonic wall. In addition, a study has been made on the influence of lactic acid on the colonic mucus and albumin permeation. Histopathologic studies of the caecum and left colon have been performed. There is a different colonic wall behaviour for each of the different isomers of the lactic and its racemic; a larger absorption of water, Na+ and Cl- for the D (-) isomer at a low concentration; its behaviour is completely opposite at high concentration. The final pH is higher when the D (-) isomer takes part; comparing the different isomers, there are small variations as far as albumin permeation is concerned. At high concentration there is a decline in Cl- absorption. The high percentage of erosions that take place especially in the caecum, where L (+) isomer can be found at high concentration, it is remarkable. The present observations suggest that the presence of lactic acid in (the) ulcerative colitis deserves great attention, especially in about the quantity and quality in which the acid can be found.

The role of short chain fatty acids (SCFA) in murine colonic carcinogenesis (MCC) has not yet been clarified. In rats, Freeman et al have reported an increased number of colonic tumors induced with dimethylhydrazine (DMH) and sodium butyrate in drinking water. On the other hand, Deschner et al showed that tributyrin intake did not increase MCC induced with azoxymethane. Both of them have reported high levels of fecal butyric acid with sodium butyrate and tributyrin intake. Although salt intake has been positively associated with colorectal cancer some authors do not support this association. We have evaluated the influence of right hemicolectomy (RH) (right colon as main source of SCFA) and the intake of 2%-pH 7 sodium butyrate (S.BUT) and 4 g/l sodium chloride (S.CHL) in drinking water, in MCC. Forty eight male Wistar rats weighing 150 g were divided into 4 groups: RH, S.BUT, S.CHL, control (C). Half of the animals received weekly DMH 20 mg/kg subcutaneously for 12 weeks. Necropsy was performed after 6 months. We have determined fecal SCFA content by gas chromatography. Neoplasm was present in 70% of rats treated with DMH. The number of animals with tumors was: RH 4/6, S.BUT 4/6, S.CHL 3/5, C 6/6. Tumor frequency was: RH 1.17 +/- 0.48, S.BUT 1.50 +/- 0.76, S.CHL 1.20 +/- 0.49, C 1.50 +/- 0.22. S.BUT group, treated with DMH, presented a lower butyric acid concentration (p < 0.05) in comparison with other groups. We have no explanation for this finding; gastric absorption of sodium butyrate may be an important factor.(ABSTRACT TRUNCATED AT 250 WORDS)

The possibility that VIP (Vasoactive intestinal peptide) could influence the enterochromaffin (EC) cell secretion of serotonin (5HT) and the action of VIP on the mast cell population of lamina propria were investigated in Wistar rat colon infused with a short chain fatty acid solution (sodium acetate), during a 1 h period. Under the action of an intravenous injection of synthetic porcine VIP, 14 micrograms/kg/h), the number of EC cells diminished significantly in the cecum and left colon, when compared to non-injected animals, both infused with a sodium acetate solution. At the same time, the number of mucosal mast cells in the crypts and lamina propria decreased significantly in the cecum. The postulate we put forward is that these VIP-induced changes are exerted through the stimulation of 5HT released from EC cells not only under normal physiological conditions but probably also under pathological conditions.

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)

The secretory response of the exocrine pancreas to an intravenous bolus of secretin (1.0 U/kg) was studied in healthy men and women below and above 45 years of age. We studied the secretory pattern, i.e., electrolyte and enzyme secretion in 8 sequential, 10-min collections and cumulative values for each parameter. Within the male group, no significant changes were observed, except for higher amylase and lipase secretions in the older subjects. On the other hand, females over 45 yr old had secretory patterns that showed a decline of flow and of bicarbonate concentration and output. No significant secretory differences were observed in the groups of younger males and females. When the over-45 groups of men and women were compared, the women exhibited a significant decrease in bicarbonate concentration and output. Moreover, this group of women had a cumulative 80-min output of bicarbonate and lipase significantly below these parameters in the men. Possible mechanisms are discussed.

An histochemical study has been made of pancreatic biopsies from 5 dogs with gastric and pancreatic Thomas cannulae. 3 dogs received 2 g kg-1 day-1 ethanol for 3, 4 and 48 months; 2 dogs which did not received alcohol served as controls. Acetylcholinesterase has been studied by the histochemical method of Koelle. Choline acetyl transferase by the method of Burt. Our results suggest that there is less acetylcholinesterase activity in the pancreas of alcoholic dogs than in control dogs. This is as more pronounced when the alcohol consumption is prolonged. On the contrary, the intensity of the histochemical reaction for choline acetyl transferase is greater in alcoholic dogs than in controls. Although histochemical methods are only semi-quantitative, these results suggest that the cholinergic tone of the exocrine pancreas is increased in chronic alcoholic dogs. This has already been suggested by previous physiological experiments performed on the same animals.

The purpose of the present work is to evaluate the action of a benzofuran derivative, Amiodarone, on an experimental acute infarction model. Six pigs were intravenously administered 1 mg/kg Amiodarone (A) 20 minutes before inducing ischemia (I) by occlusion of the anterior descending coronary artery, which was maintained for 90 minutes. A similar dose level was repeated 20 minutes before ligation release (R). Similarly, another six animals received a placebo and formed the Control Group (C). The extent of myocardial injury was assessed by summations of ST segments (Sigma ST) and R (Sigma R) and Q (Sigma Q) waves of electrocardiographic epicardial mappings, as well as by serum levels for SGOT and LDH. Systemic blood pressure, pulmonary pressure, right atrial pressure, systemic resistance and cardiac output were also controlled. Two hundred and ten minutes after R, the animal was sacrificed for the purpose of carrying out morphological and histochemical studies. No significant differences were observed in the blood pressure of either group. During I, systemic resistance values suffered a drop in the Amiodarone Group A, whereas they increased in both groups after reperfusion. Pulmonary pressure was higher in Group A. Cardiac output showed a similar behavior in both groups up to R, when it significantly decreased in animals receiving Amiodarone. The Sigma ST and the Sigma Q were higher in the Control Group C, whereas the Sigma R was higher in Group A. The SGOT and LDH levels were higher during R in Group C. Histochemistry showed a higher activity for SDH and LDH in treated animals. Due to its action on afterload, its contractility and its direct myocardial action, Amiodarone limited the extent of necrosis and increased the recoverable amount of myocardium.

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.

In rats, a secretin (Jorpes) intravenous infusion superimposed on an intracolonic sodium acetate perfusion elicits, with respect to control values, a significant depression of Na+ absorption (0.16 mEq./h-0.00 mEq./h.) and mucus secretion (230-40 mg.). When the hormone is superimposed upon an intracolonic infusion of acetic acid, mucus secretion is also significantly inhibited (790-340 mg.). The influence of secretin on organic anion movement was pH related. At pH values of 7.0, absorption was unchanged (0.34--0.33 mEq./h.), at pH values of 2.9, absorption was significantly reduced (0.67-0.41 mEq./h). The secretin impairment of colonic mucus secretion could influence the transport of watersoluble (Na+) and lipid soluble (acetic acid) substances, probably through changes at the "unstirred layer" level.

We studied mucin histochemistry in 25 rectosigmoid adenocarcinomas and in the transitional mucosa adjacent to these tumors using standard techniques for the detection of neutral and acid sialomucins and sulfomucins and the paradoxical concanavalin A (Con A) stain. This histochemical procedure selectively detects residues of mannose in glycoproteins exposed to brief steps of oxidation and reduction. Those techniques were also used to study histologically normal mucosa of specimens with carcinoma, normal rectosigmoid mucosa of patients without inflammatory or neoplastic bowel disease, hyperplastic rectal polyps, and rectosigmoid mucosa of human fetuses. Normal mucosa and hyperplastic polyps mainly contained sulfomucins and did not display Con A binding activity with any of the variants of the stain. In contrast, fetal, transitional, and malignant mucosa predominantly showed sialomucins and although not reactive with the standard Con A sequence, displayed binding activity for the lectin after short oxidative-reductive steps. These results provide further evidence that transitional and malignant mucosa produce markedly abnormal mucins whose histochemical patterns represent a re-emergence of the fetal type found during development. The principles of the paradoxic Con A reaction may be applied to unmask lectin binding activity in apparently unreactive sites.

The effects of chronic truncal vagotomy on the pancreatic gland was studied in male adult Wistar rats. Two to three months after parasympathetic decentralization, the gland weight was found to be significantly increased by nearly 100%. This trophic effect is mainly due to the proliferation of young acinar cells. Concomitantly, there is a decrease of the ductular mass and of the Langerhans islets. Choline acetylase activity was decreased by about 35% to 40% in the vagotomized pancreas. Further, enzyme concentration was found to be greater in the head than in the body and tail of the gland, thus suggesting a higher nerve density of vagal cholinergic fibers in the former than in the latter. Basal pancreatic secretion of the decentralized gland showed a significant increase in the flow rate with no significant changes in both bicarbonate concentration and output. Protein concentration was significantly reduced at 60 minutes; protein output remained unchanged. The most remarkable finding was the fall in both lipase concentration and output (60-70%) when compared with control values. These findings may be related to clinical manifestations after long-term vagotomy.

Pirenzepine has been widely used for the treatment of gastric and duodenal ulcer. In this work we have proved that this drug could prevent the inflammatory reaction induced in the colon with an intraluminal stimuli as the acetic acid. These data suggest the cholinergic participation in the inflammatory colonic response.