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Biomedical subjects

J F Grenier

Publications and source records attributed to J F Grenier.

At least 55 records · Page 3Linked to original sources

Effect of chronic alcohol administration on the exocrine pancreas after jejunoileal bypass in the rat.

To determine whether intestinal bypass operation and alcohol administration exerted a synergistic effect on pancreatic enzyme composition and morphology, adult rats were submitted either to a sham-operation or to a 90 per cent jejunoileal bypass. Two weeks after the operation, the rats received a 15 per cent solution of ethanol in drinking fluid during a period of four weeks while controls received water. In sham-operated animals, alcohol had no effect on pancreatic weight or its total content in protein and amylase. The general structural and ultrastructural aspect remained unchanged except for the presence of a few mixed acinar-islet cells. Bypass operation alone induced a significant decrease in amylase content while the population of zymogen granules was reduced. Parallely, lipid droplets deposited within acinar cells. Alcohol administered in bypassed animals exerted a synergistic effect on fat accumulation in pancreatic acinar cells but had no effect on other biochemical and morphological parameters.

Amylases↗

Copper accumulation in primary biliary cirrhosis. An electron and X-ray microanalytical study.

Ultrastructural and X-Ray microanalytical aspects of primary biliary cirrhosis were analysed and compared to those of normal liver. Electron microscopic studies showed a significant increase of dense lipofuscin-like granules in PBC compared to the hepatocytes of normal liver (665%). These granules (0.3-2.7 micrometers in diameter) were formed by the association of primary lysosomes and lipid droplets. X-Ray microanalysis of these structures showed the presence of Calcium, Phosphorus, Potassium, Chlorine, Sulphur, Aluminium and Copper. The coexistence of Sulphur with other mineral elements suggests the occurrence of metalloproteins binding these elements. These findings provide evidence that intralysosomal sequestration of mineral elements, especially copper protects the hepatocytes from cytotoxic effects.

Copper↗

Organ culture of suckling rat intestine: comparative study of various hormones on brush border enzymes.

Jejunal mucosa of 6 d-old rats were cultured for 24 and 48 h in the presence of thyroxine, insulin, pentagastrin, glucagon, epidermal growth factor (EGF) or dibutyryl-A-3:5-MP cyclic with or without dexamethasone (DX). The enzymes were assayed on the purified brush borders. The various agents added alone to the basic culture medium had no effect with the exception of DX on the levels of enzyme activities. Dexamethasone alone induced sucrase, stimulated maltase, and protected other brush border enzyme activities (aminopeptidase, lactase, and alkaline phosphatase). When added to DX-supplemented medium, only the following factors modified the levels of enzymatic activities observed with DX alone. Insulin (10(-6) M) increased maltase, alkaline phosphatase, and lactase activity to a greater extent than DX at 24 h culture, the effect being maintained at 48 h on alkaline phosphatase only. At 48 h culture, both EGF (10(-8) M) and dbcAMP (10(-3) M) decreased DX-induced sucrase activity. The latter agent also depressed DX-stimulated aminopeptidase activity.

Alkaline Phosphatase↗

Control of brush border enzymes by dexamethasone in the fetal rat intestine cultured in vitro.

The effect of dexamethasone (DX) on the prenatal maturation of rat intestinal brush border enzymes was studied in organ culture. Jejunal segments were explanted daily from day 17 of gestation until birth, as well as at different postnatal stages until day 6; they were cultured for 48 h with or without DX (8 X 10(-8) M). Enzymatic activities were analyzed on brush border membranes purified from cultured intestines and were compared with values from uncultured specimens. The results showed that DX elicited (a) a precocious induction of sucrase activity in the jejunum explanted from 19 days of gestation onward, reaching a peak value when taken at birth; (b) a stimulation of maltase activity in the segments explanted as soon as day 18, leading to maximal values when taken at day 20, the stage at which the stimulated activity reached a 6.5-fold increase over the baseline activity; and (c) an increase of lactase activity comparable to that occurring in utero. As opposed to this, DX has no specific action on alkaline phosphatase and aminopeptidase activities. The present data indicate that glucocorticoids directly and specifically influence the prenatal maturation of some brush border enzymes in the mammalian gut.

Alkaline Phosphatase↗

Effects of prolonged alcohol administration and a high carbohydrate-low protein diet on the activities of the jejunal brush border enzymes in the rat.

The effects of prolonged alcohol administration were studied on the brush border enzyme activities of the jejunum in rats receiving either a normal laboratory diet or a high carbohydrate-low protein for several weeks. Alcohol (15%) given in association with the normal diet provoked a stimulation of sucrase, maltase, and lactase activities after four weeks, but no significant modification in aminopeptidase activity. These results obtained for the disaccharidases were very similar to those observed with the high carbohydrate-low protein diet given without alcohol, although major differences were obvious in the timing of enzyme stimulation. In contrast, this dietary condition initiated a drop in aminopeptidase activity. When alcohol was given in association with the high carbohydrate-low protein diet, no modification in aminopeptidase activity was detected and the stimulation for the disaccharidase activities was similar to that observed with the high carbohydrate-low protein diet given alone. The present results suggest that the mechanisms involved in the stimulation of brush border disaccharidase activities were different for alcohol and for the high carbohydrate-low protein diet.

Animals↗

Effect of chronic alcohol administration on liver morphology and on brush border membrane enzymes after jejunoileal bypass operation in rat.

To determine whether jejunoileal bypass operation and alcohol administration exerted a synergistic effect on the activities of brush border membrane enzymes and on liver morphology, adult rats where submitted either to sham operation or to jejunoileal bypass operation. 2 weeks after operation the rats received a 15% solution of ethanol during a period of 4 weeks, controls received water. In the sham-operated rats, alcohol provoked stimulation of the disaccharidase activities in the proximal jejunum but had no effect on these activities in the ileum. Bypass operation alone induced a significant increase in sucrase activity in the functioning ileum but had no effect on the jejunal disaccharidase activities. Alcohol administered after bypass provoked a further increase in ileal brush border sucrase activity. The increase of the brush border enzyme specific activities in the excluded loop resulted from the important protein loss observed in this segment. Alcohol alone or bypass operation by itself had little effect on liver morphology. In contrast, when associated they induced extensive accumulation of fat droplets in the hepatocytes. Since alcohol is frequently associated with the diet in man, alcohol should be considered as an important contributing factor to intestinal enzyme adaptation and liver dysfunction after jejunoileal bypass operation.

Aminopeptidases↗

Modifications of brush border enzyme activities during starvation in the jejunum and ileum of adult rats.

Aminopeptidase, lactase and sucrase activities have been followed during 5 days in the jejunum and in the ileum of starved adult rats. Enzyme activities have been determined in the mucosal homogenates as well as in the purified brush border membranes and expressed as activities per intestinal length (segmental activities) or as activities per milligram of protein (specific activities). The segmental and specific activity of aminopeptidase was increased in the ileum during the first 2 days of starvation, suggesting that aminopeptidase may have during the first days of starvation a conservative role by preventing an important loss of tissue protein. In all conditions, lactase activity was strikingly enhanced by starvation whereas sucrase activity showed no changes or decreased activity. Lactase stimulation was initiated during the first 24 h of starvation reaching its maximum after 2 days. The various experimental conditions leading to a specific or to a nonspecific stimulation of intestinal lactase activity have been discussed.

Animals↗

Effect of small bowel bypass on the rat exocrine pancreas.

Biochemical, structural, and functional studies of the exocrine pancreas were performed in adult male Wistar rats over a 3-month period following a 90 per cent jejunoileal bypass or sham operation. The wet weight of the gland, its content in total protein and DNA, as well as its structural organization were similar in both groups. The enzyme content was globally reduced after bypass surgery. However, amylase was much more and earlier affected than lipase and chymotrypsinogen. In addition, zymogen granules diminished in size while lipid droplets deposited in acinar cells. Enzyme secretion stimulated or not by increasing concentrations of caerulein in vitro was generally reduced after intestinal bypass and approximately parallel to the depressed amount of enzymes in the pancreas. These findings suggest that jejunoileal bypass does not modify the size of the rat pancreas despite protein deficiency, but its enzymatic composition and secretory function is altered.

Amylases↗

[Permissive effects of human colonic cancer (HT-29 and Caco-2) on intestinal smooth muscle differentiation].

Human colonic carcinoma cells (lines HT-29 and Caco-2) were associated with 5 1/2 day-old chick embryonic intestinal mesenchyme and grafted for 11 days into 3 day-old Chick embryos. In these conditions, the cancer cells exert on the mesenchyme a supportative effect leading to its differentiation into muscular layers. The results provide additional evidence that HT-29 and Caco-2 cells exhibit common properties to fetal and normal intestinal cells.

Animals↗

BSP clearance as the most reliable criterion of hepatic dysfunction after jejunoileal bypass in the rat: arguments in favor of the existence of a pathogenetic mechanism involving a transient malnutrition state.

In rats subjected to 90% jejunoileal by-pass or in sham-operated controls, liver function was compared to plasma nutritional state and adaptation of the intestine in continuity over a period of 3 months. While the plasma levels of GOT, GPT, and esterases A and C as cholinesterase C did not differ in either group, the percentage of retention of BSP increased until 8 weeks, then returned progressively to control values 12 weeks after small-bowel bypass. In contrast, plasma nonesterified fatty acid levels decreased significantly until 6 weeks, then recovered control values over the following periods. Plasma total protein and albumin levels also diminished after jejunoileal bypass, the most marked decrease being at the 4th postoperative week. The increase in villus size following the intestinal bypass was considered pronounced for the ileum between the 8th and the 12th week. These results suggest that BSP clearance is the most reliable criterion for hepatic dysfunction in the rat subjected to a jejunoileal bypass. In addition, the parallelism between the variations of BSP clearance, intestinal adaptation, and plasma nutritional state argue for the "nutritional" theory as the most probable explanation for the formation of hepatic lesions.

Animals↗

Hyperplasia of the exocrine pancreas after small bowel resection in the rat.

The effect of a 90% small bowel resection on the exocrine pancreas was investigated over a three month period in adult Wistar rats. Control animals underwent a sham-resection consisting of a transection and reanastomosis of the small intestine. After jejunoileal resection, the wet weight of a gland increased significantly (52%) from the 15th day. The parallel increase in total protein, DNA and RNA content without any modification in the ratios of pancreatic weight, protein, and RNA to DNA suggests that there is cellular hyperplasia but not hypertrophy. Small intestinal resection decreased significantly the amount of amylase when expressed per unit pancreatic weight; it reduced slightly but not significantly that of chymotrypsin, while it did not modify the amount of lipase. However, the total amount of these enzymes in the pancreas remained unaltered when compared with controls. It is concluded that a massive resection of the small bowel induces cellular hyperplasia in the rat exocrine pancreas; this could compensate that reduced level of enzymes in acinar cells.

Adaptation, Physiological↗