Alcohol-induced liver injury after jejunoileal bypass operation in rats

The objective of this study was to investigate whether alcohol administration exerts a synergistic effect on jejunoileal bypass-induced liver dysfunction in rats. Male Wistar rats were subjected to 90% jejunoileal bypass or sham operation. For 10 weeks, subgroups were pair-fed either an alcohol-containing (36% of total calories) liquid diet or a liquid diet where alcohol was replaced isocalorically by starch. Alcohol feeding in rats with jejunoileal bypass increased hepatic triglyceride content about 6-fold as compared with bypassed rats receiving control diet. Neither jejunoileal bypass nor alcohol feeding led to significant changes in hepatic DNA and protein contents. Alcohol feeding increased cytochrome P-450 levels both in operated and in sham-operated rats. The administration of alcohol-containing diet decreased the activity of succinic dehydrogenase, the decrease being distinctly more pronounced in rats with jejunoileal bypass than in the sham-operated controls. Light microscopy revealed no significant morphological alterations in liver sections of rats fed the control diet after jejunoileal bypass or of rats receiving either the alcohol-containing diet or the control diet after sham operation. Alcohol feeding in bypassed rats, however, produced marked diffuse accumulation of fat, and regularly led to other histological abnormalities in the liver. These abnormalities included ballooning of hepatocytes and disarray of the trabecular structure of the liver lobule, hyalin inclusions resembling megamitochondria, single-cell necrosis and focal clustering of necrosis, increased number of mitotic figures, and infiltrates with inflammatory cells. The histological lesions of the liver of bypassed rats receiving alcohol exhibited no obvious zonal distribution. The results demonstrate that alcohol feeding to rats subjected to jejunoileal bypass leads to marked liver injury which mimics, at least in part, that of alcohol-induced liver disease in man. Rats subjected to jejunoileal bypass may, therefore, provide a new model for the study of alcoholic liver disease.     

The effect of jejunoileal bypass (JIB) in the obese Zucker rat on a sub-group of enteroendocrine cells

The effect of jejunoileal bypass in lean and obese Zucker rats on a number of enteroendocrine cell types was investigated 5 weeks following surgery to remove 80 percent of the small bowel from continuity. The endocrine cells containing somatostatin, cholecystokinin, gastric inhibitory polypeptide, enteroglucagon and neurotensin were investigated. In control rats enteroglucagon cell number was decreased in obese compared to lean animals (5 +/- 1 vs 11 +/- 1 cells/mm). Following jejunoileal bypass the enteroglucagon cell population increased two-fold in both the functional and bypassed bowel in obese rats but was not elevated in lean animals. A significant increase in the number of cholecystokinin cells in the bypassed loop of the jejunum in both lean and obese bypassed rats was observed. The cholecystokinin cell population was also markedly elevated in the functional jejunum of obese but not lean bypassed rats. Only small changes were noted in cell numbers of gastric inhibitory polypeptide, somatostatin and neurotensin containing cells, suggesting that individual cell types have specific stimuli for proliferation. Epithelial height, a measure of intestinal adaptation, was similar in lean and obese rats in both the control and bypassed states, but weight loss in obese bypassed animals was significantly greater than that of lean bypassed rats. The hyperinsulinemia of obese rats was only partially normalized by jejunoileal bypass. These data indicate that jejunoileal bypass has effects on specific enteroendocrine cells which differ between lean and obese Zucker rats, and between individual cell types.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic factors are trophic in bypassed rat small intestine in the absence of luminal contents.

Mucosal histology, crypt cell proliferation and brush border enzymes were measured in rats with varying degrees of jejunoileal bypass, in order to compare the effect of systemic and luminal factors on adaptive growth and differentiation (brush border enzymes) in small intestinal epithelium. Eighty five percent jejunoileal bypass caused a functional short gut; in intestine remaining in continuity there were significant increases in segmental weight, villus area and crypt depth, compared with sham operated controls and 25% jejunoileal bypass rats. Despite villus cell hyperplasia in 85% bypass rats, mucosal sucrase and alkaline phosphatase fell in jejunum and remained low in ileum, while leucine amino peptidase rose in ileum. There was a significant fall in villus area (p less than 0.01) and crypt cell production (p less than 0.001) in self emptying loops of 25% bypass rats not exposed to luminal contents compared with control segments of sham operated rats. In contrast, self emptying loops of 85% bypass rats were not atrophied despite the much greater distance from luminal nutrients; the villus area (p less than 0.01) and crypt cell production (p less than 0.005) were higher than in 25% bypass rats, and at least as great as in sham operated rats. These results indicate that adaptive hyperplasia has a variable effect on expression of brush border enzymes which might reflect villus cell immaturity. The atrophic effect of diversion of luminal contents can be counteracted by systemic growth factors released as part of the adaptive response; thus systemic growth factors are not dependent on a permissive effect of luminal contents.     

Intestinal bypass. Bacteriological studies from different parts of the small intestine in rats

Forty-five rats were divided into four groups according to type of operation: 1) end-to-side jejunoileal bypass (ES), 10 rats; 2) end-to-end jejunoileal bypass (EE), 10 rats; 3) jejunoileal resection (R), 10 rats; and 4) no operation, 15 rats. The luminal contents from the proximal jejunum and distal ileum, in groups 1 and 2 also from the proximal and distal part of the excluded small intestine, were examined bacteriologically 5-11 months after operation. The total number of aerobic and anaerobic microbes in the jejunum was equal in all groups. The number of aerobic bacteria in the ileum was significantly higher in the ES group than in the R and U groups. The number of bacteria capable of producing gas in glucose-supplemented media was increased both in the jejunum and ileum after ES bypass. Enterobacteriaceae and Bacteroides were commonly present in the ileum after both types of bypass but were not cultured in jejunal contents. The proximal part of the excluded intestinal segment in groups 1 and 2 contained very low numbers of microbes, whereas the flora of its distal part was similar to that of the ileum in continuity in group 1. Thus, the most marked changes of the intestinal flora occurred after ES bypass in the region of the anastomosis and distal to this.     

Cyclic motor activity and trophicity after jejunal resection and bypass in rats

The aim of the study was to examine the changes in intestinal motility induced by an extensive jejunal resection and bypass in rats using an electromyographic technique. The relationship, if any, between the development of motility and adaptive modifications of intestinal trophicity was also studied. A massive jejunal resection, preserving a 7-cm segment distal to the ligament of Treitz, was performed in one group of animals. In a second group, the jejunum was bypassed as a self-emptying blind loop. Two sham-operated groups underwent transection and reanastomosis on the proximal jejunum or ileum. Electromyographic activity was studied at the 10th and 30th postoperative days by means of electrodes implanted throughout the remaining or bypassed bowel and was expressed by means of the pattern of recurrence of the migrating myoelectric complex (MMC). After a month, the animals were sacrificed. Mucosal and muscular wet weight and protein content (mg/cm) of the intestine were then determined. The results showed that 10 days after the jejunal resection in the fasting state, MMC cycle duration is different in the remaining jejunum and in the ileum. However, the distribution of MMC phases in the jejunum was modified and was similar to the one in the ileum. Thirty days after resection, MMC cycle duration, as well as phase distribution in the remaining jejunum, resemble the MMC patterns in the ileum. These changes were not observed after bypass. After the return of MMCs after postprandial inhibition produced by a meal, MMC duration in the ileum was greatly decreased until a month after jejunal resection. In contrast, the jejunal bypass did not produce this modification.     

Goblet cell hyperplasia is a feature of the adaptive response to jejunoileal bypass in rats

The role of goblet cells in the adaptive response of the intestine to jejunoileal bypass was studied in rats submitted to an 85% end-to-side jejunoileal bypass or sham bypass. At 36 weeks the length and wet weight of the duodenum and large bowel was 13-48% greater in animals with jejunoileal bypass. Measurements of villous height and crypt depth confirmed mucosal hyperplasia in the residual functioning small bowel and the distal colon. Histochemical studies in both groups of rats showed an overall predominance of sulphomucins throughout the intestinal tract, but jejunoileal bypass caused a disproportionate increase in the number of sialomucin containing goblet cells in functioning segments of small bowel and distal colon. An abundance of sialomucin cells at the site of anastomosis after jejunoileal bypass may have been a protective response to local mechanical trauma. Goblet cell hyperplasia is a feature of compensatory growth of the intestinal tract after surgical shortening. The changes in colonic mucin seen after jejunoileal bypass resemble those observed in ulcerative colitis and mucosal dysplasia.     

Pathophysiology of small intestinal malabsorption in gerbils infected with Giardia lamblia.

Mongolian gerbils were infected with a human pathogenic Giardia lamblia strain and compared with sham-treated control animals 6 days after inoculation. Infection resulted in crypt hyperplasia associated with an increased enterocyte migration rate. Villus height was decreased in the duodenum, unchanged in the jejunum, and increased in the ileum of infected animals. Epithelial microvilli were markedly shortened, and brush border surface area decreased in the jejunum and ileum of infected animals. Thymidine kinase activity was increased in isolated duodenal villus enterocytes but did not differ in the jejunum and ileum. In vitro and in vivo experiments showed that the infection resulted in decreased jejunal glucose-stimulated electrolyte, water, and 3-O-methyl-D-glucose absorption, whereas in the ileum in vitro electrolyte and 3-O-methyl-D-glucose absorption was similar in infected and control animals. Thus, in the jejunum infection causes electrolyte, solute, and fluid malabsorption associated with decreased brush border surface area. The results indicate that the diarrhea associated with giardiasis is caused by malabsorption rather than active secretion.     

Effects of Extrinsic Denervation With or Without Ischemia–Reperfusion Injury on Constitutional Mucosal Characteristics in Porcine Jejunoileum

We investigated the effects of jejunoileal denervation with or without ischemia–reperfusion on mucosal characteristics and small intestinal structure. Growing pigs underwent sham laparotomy, jejunal transection, or extrinsic jejunoileal denervation with or without in situ ischemia–reperfusion. Small intestinal morphology, crypt cell proliferation, enterocyte ultrastructure, and disaccharidase activities were analyzed from jejunum and ileum after eight weeks. Immunohistological analysis of the ileum showed no staining of catecholaminergic neurons after extrinsic denervation. Neural isolation of the jejunoileum with or without ischemia–reperfusion injury reduced weight gain and villous enterocyte density in the ileum, abolished the proximodistal gradient of sucrase activity, and increased mucosal thickness, villus height, and villus surface area in the ileum. However, gross jejunoileal morphology, crypt cell proliferation, and enterocyte ultrastructure remained unchanged. In conclusion, jejunoileal denervation in growing pigs selectively modulates constitutional mucosal characteristics in the ileum, presumably due to altered enterocyte turnover, without a decrease in small intestinal absorptive surface area. These changes are independent of short ischemia and subsequent reperfusion.     

Morphometric study of the small intestinal mucosa in young, adult, and old rats submitted to protein deficiency and rehabilitation.

Linear and stereological morphometric methods were applied to the jejunal and ileal mucosa of young, adult, and old male Wistar rats submitted to protein deficiency and rehabilitation. The animals were fed ad libitum a 2% casein diet during 42 days and then received a 20% casein diet for 30 days. Food intake, body weights, and plasma protein concentrations were recorded. In the young protein deficient rats values of mucosal height, surface area, and volume of the lamina propria were significantly lower than those of their age controls in both jejunum and ileum. In adults the differences were less marked and in the old rats all parameters were found to be unaltered by the protein deficient diet. The surface-to-volume ratio showed no significant differences between control and protein deficient in all three age groups, meaning that villus pattern did not change with protein deficiency. On rehabilitation, a striking difference between jejunum and ileum was observed in the young rats; all parameters returned to control levels in the jejunum, while they remained lower than those of their controls in the ileum.     

BSP clearance as the most reliable criterion of hepatic dysfunction after jejunoileal bypass in the rat

In rats subjected to a 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 considerably 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.     

Age related increase of brush border enzyme activities along the small intestine.

Intestinal morphology and brush border hydrolase activities were determined along the small intestine of young adult (three months, n = 10), mature (12 months, n = 10), and senescent (29 months, n = 15) rats. The intestinal segments of the senescent rats contained higher mucosal mass and protein content (p less than 0.05) compared with the young and mature animals. A significant reduction of villus height and crypt depth (p less than 0.05) was found in the proximal intestine during aging. A 35% increase in villus height (p less than 0.05) without changes in crypt depth, was observed in the distal ileum in senescent rats. The activities of sucrase and isomaltase were significantly increased during aging in the duodenum and jejunum (p less than 0.05). Lactase and aminopeptidase activities which showed only minor changes between young and mature animals were significantly enhanced in senescent animals (p less than 0.05) with aminopeptidase exhibiting a three-fold increase in activity in the proximal ileum. The results when combined with those of previous studies suggest that in the aged animal, the increased level of intestinal hydrolase activities may be the consequence of prolonged cellular maturation along the villi in the proximal intestine, and of adaptation to increased concentrations of intraluminal substrates in the distal intestine.     

Small bowel bypass prevents the trophic action of cholecystokinin on the rat pancreas

The effect of a chronic administration of cholecystokinin (CCK) on the rat pancreas has been studied in rats subjected to a 90% jejunoileal bypass or an intestinal transection (controls). Jejunoileal bypass, when compared to transection, did not modify the size of the pancreas but decreased its enzyme content, especially for amylase, and reduced the number of zymogen granules. These structural and biochemical changes were maintained when bypassed animals were treated three times daily and for six days with cholecystokinin (20 Ivy Dog Units (IDU)/kg). In contrast, CCK treatment in transected animals induced growth of the pancreas due to cellular hypertrophy and hyperplasia; pancreatic enzyme content, especially for chymotrypsin, and the population of zymogen granules in acinar cells were also enhanced. It is concluded that jejunoileal bypass prevents the trophic action of chronic CCK on the pancreas.     

Modifications of the trophism of intestinal mucosa after intestinal and bilio-pancreatic diversion in the rat.

Morphofunctional alterations to the intestinal mucosa are influenced by three main factors: food, bilio-pancreatic secretions, intestinal hormones. In order to assess the importance of each one, histological and histochemical tests were performed on different segments of intestine taken from rats which were sacrificed one month after the following procedure: gastrojejunal anastomosis on a Roux loop (Model I); same procedure plus biliopancreatic bypass into the jejunum (Model II). When compared to the controls, Model I duodenum samples revealed hypertrophy of the entire wall with "bundles" of villi, while Model II samples showed a clear hypotrophy and reduction in the number of duodenal villi. To such modifications of the duodenum correspond longer, thinner villi in the other bowel segments, particularly in the jejunum and distal ileum. These results suggest that the predominant trophic effect derives from contact with biliopancreatic secretions at a proximal level. The modifications of the duodenal mucosa appear to regulate the trophism of the distal segments probably by the secretion of distant acting enterohormones.     

Dietary fat content influences uptake of hexoses and lipids into rabbit jejunum following ileal resection

After 6 weeks' feeding on a high-fat or low-fat diet, the in vitro uptake of hexoses and lipids was measured in control rabbits with an intact intestinal tract, and in animals submitted to the surgical removal of the distal half of their small intestine. Jejunal villus height, villus surface area and mucosal surface area were higher in unresected control rabbits fed the low- as compared with the high-fat diet, whereas dietary fat content had no effect on villus morphology in resected animals. Mucosal surface area was similar in control and in resected animals fed the high-fat diet, but was lower in resected than in control animals fed the low-fat diet. The active and passive transport properties of the jejunum were influenced by dietary fat manipulation. These absorption changes were qualitatively and/or quantitatively different in animals with an ileal resection from those in animals with an intact small intestine. Dietary fat manipulation had a different effect on the uptake of each lipid probe. The effective resistance of the intestinal unstirred water layer also adapted to changes in the dietary content of fat, but the changes in uptake of hexoses, fatty acids and cholesterol cannot be simply explained by alterations in this diffusion barrier, or by changes in the villus morphology. These findings indicate the importance of dietary fat on villus structure and transport function and their adaptation to ileal resection.     

Fasting and meal-stimulated plasma levels of neurotensin in obese patients after jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio

The functional role of the jejunum and ileum with regard to peripheral plasma levels of intact neurotensin and NH2-terminal immunoreactivity of neurotensin was studied by using jejunoileal bypass as a model. Plasma levels were measured by radioimmunoassay before and after jejunoileal bypass randomized to different jejunoileal ratios. Seven patients were studied before bypass surgery and 28 were examined after end-to-side jejunoileal bypass with 50 cm intestine in continuity and a 3:1 or 1:3 ratio between the length of the jejunal and ileal segments. Fasting levels of intact neurotensin were unchanged by surgery, whereas levels of NH2-terminal immunoreactivity were higher in bypass patients with a long ileal segment (37.5 cm) than in unoperated patients and in those with a short ileal segment (12.5 cm). Meal-stimulated levels of intact neurotensin were higher after 1:3 than 3:1 jejunoileal bypass. The levels of NH2-terminal immunoreactivity in patients with a short ileal segment and in controls were lower than in patients with a long ileal segment. The results show that postprandial levels of both intact neurotensin and NH2-terminal immunoreactivity are related to the length of the functioning ileum and that even a difference in length of 25 cm is reflected in the circulating levels of neurotensin.     

Effect of phytohemagglutinins on cell proliferation of the small intestine epithelium of rats]

Twenty male rats, were divided into two groups of ten animals each: E group, which received solid diet containing 4% of phytohemagglutinin and P group iso-caloric par-fed control, which received the same diet but the phytohemagglutinin was inactivated by heat. Water was offered ad libitum to all groups. The animals were weighed every day and the consumption of diet and water was registered. In the fourteenth day of experiment, the animals were sacrificed and the fragments of jejunum and ileum were removed to morphokinetic study. The results showed that the hydric ingestion was the same in both groups, the body weight of the E group was significant smaller than P group, the villus cell population from the jejunum of the E group was statistically smaller than P group and the contrary happened with ileum samples, wherein the E group was statistically larger than P. The jejunum villus height from E group was similar with P group, but in the ileum of the E group was larger than P. The depth, the cell population and cell production rate of crypt of E group were larger than P, in the jejunum and in the ileum. In conclusion, these results in the present study supply evidence that the intake of the phytohemagglutinin provokes injury of jejunal mucosa, reducing the villus cell population and stimulating the crypt hyperplasia, developing local adaptation. This adaptative model is similar to the one that occurs in celic disease. This proximal lesion stimulate crypt-villus unit hyperplasia of the ileal epithelium, developing distal adaptation. These adaptations occurred in animals that ingested phytohemagglutinin, even though with multicarencial malnutrition.     

Insulin-like growth factor and insulin receptors in intestinal mucosa of neonatal calves

Intestinal development is modified by age and nutrition, mediated in part by insulin-like growth factors (IGF-I, IGF-II) and insulin. We have investigated whether expression of IGF-I, IGF-II and insulin receptors (IGF-IR, IGF-IIR and IR; measured by real-time RT-PCR) and binding capacity (Bmax) of IGF-IR, IGF-IIR and IR in the mucosa of the small and large intestine of neonatal calves are modified by age and different feeding regimes. In experiment 1, pre-term (GrP) and full-term (GrN) calves (after 277 and 290 days of pregnancy respectively) were killed immediately after birth before being fed; a further group of full-term calves were fed for 7 days and killed on day 8 of life (GrC(1-3)). In experiment 2, full-term calves were killed on day 8 after being fed first-colostrum for 7 days (GrCmax), colostrum of the first six milkings for 3 days (GrC(1-3)) or milk-based formula for 3 days (GrF(1-3)). Intestinal sites differed with respect to expression levels of IGF-IR (duodenum>jejunum in GrC(1-3); ileum>colon, duodenum> or = jejunum in GrF(1-3)), IGF-IIR (colon>duodenum and ileum in GrN), and IR (lowest in ileum in GrP and CrN; highest in colon in GrC(1-3) and GrCmax). They also differed with respect to Bmax of IGF-IR (ileum and colon>duodenum and jejunum in GrP; ileum and colon>jejunum in GrN; colon>jejunum in GrC(1-3); lowest in jejunum in GrF(1-3)), IGF-IIR (duodenum and colon>jejunum and ileum in GrP; duodenum>ilem and colon>jejunum in GrN; duodenum, jejunum and colon>ileum in GrCmax, GrC(1-3), and GrF(1-3)) and IR (ileum>duodenum, jejunum and colon in GrCmax, GrC(1-3), and GrF(1-3)). There were significant differences between groups in the expression of IGF-IR (GrF(1-3)> GrCmax and GrC(1-3) in ileum), IGF-IIR (GrN>GrP and GrC(1-3) in colon; GrN>GrC(1-3) in jejunum and total intestine), and IR (GrCmax>GrF(1-3) in colon) and in the Bmax of IGF-IR (GrP>GrN in colon; GrCmax>GrF(1-3) in jejunum), IGF-IIR (GrN>GrP in duodenum, ileum and total intestine; GrN>GrC(1-3) in duodenum, ileum, colon and total intestine) and IR (GrN>GrP in total intestine; GrC(1-3)>GrN in ileum and total intestine). In addition, Bmax values of IGF-IR, IGF-IIR and IR were correlated with villus circumference, villus height/crypt depth and proliferation rate of crypt cells at various intestinal sites. There were marked differences in Bmax of IGF-IR, IGF-IIR and IR dependent on mRNA levels, indicating that differences in Bmax were the consequence of differences in posttranslational control and of receptor turnover rates. In conclusion IGF-IR, IGF-IIR and IR expressions and Bmax in intestinal mucosa were different at different intestinal sites and were variably affected by age, but not significantly affected by differences in nutrition. Receptor densities were selectively associated with intestinal mucosa growth.     

Regulation by dietary calcium of vitamin D-dependent calcium-binding protein and active calcium transport in the small intestine of lactating rats

To test the hypothesis that vitamin D-dependent calcium-binding protein (CaBP) and active calcium (Ca) transport in the small intestine of vitamin D-replete lactating rats are regulated by dietary Ca intake, pregnant rats were given a high Ca (1.6% Ca and 1.4% phosphorus) or low Ca (0.1% Ca and 0.4% phosphorus) diet starting 3 days before delivery. Toward the end of lactation (days 16-23) the rats were killed, and active Ca transport (using everted gut sacs) and CaBP were determined in duodenum, jejunum, and ileum. The right tibiae were used for bone weight and ash determinations. The Ca transport ratios and CaBP concentrations in jejunum and ileum were significantly increased only in the low Ca group. In contrast, in the duodenum both parameters were equally high regardless of the diet. Nonlactating rats given the two diets for the same length of time had the expected increase in both parameters in the duodenum when fed the low Ca diet. Nonlactating rats, in contrast to lactating rats, had undetectable CaBP in jejunum and ileum regardless of diet. Lactating rats fed the high Ca diet had no net loss of bone at the end of lactation compared with rats on day 1 of lactation. In contrast, lactating rats fed the low Ca diet had a net loss of 44% of bone weight. Plasma 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] concentrations on the 21st day of lactation were (mean +/- SE) 538 +/- 96 and 46 +/- 18 pg/ml in rats consuming the low and high Ca diets, respectively. The comparable values for the nonlactating rats were 140 +/- 4 and 26 +/- 8 pg/ml. In conclusion, dietary Ca restriction during lactation can stimulate CaBP and active Ca transport in both jejunum and ileum, and both parameters appear to be modulated by dietary Ca via the circulating concentration of 1,25-(OH)2D3. In contrast, in the duodenum neither parameter appears to be related to dietary Ca, plasma 1,25-(OH)2D3 concentration, or lactation-associated bone loss.     

Effect of acute Yersinia enterocolitica infection on small intestinal ultrastructure

The purpose of this study was to assess the jejunal and ileal brush border injury caused by Yersinia enterocolitica and to correlate these alterations with functional abnormalities. Weanling rabbits infected with 10(10) organisms of a human pathogenic Y. enterocolitica strain were compared with control and pair-fed, sham-treated animals. On day 6, infection resulted in a diffuse decrease in brush border enzyme activities in the small intestine and villus atrophy and crypt hyperplasia in the ileum. By day 14, ileal architecture and jejunal disaccharidases had returned to normal, but enzyme abnormalities persisted in the ileum. Ultrastructural studies showed decreased brush border surface area in the jejunum and ileum on day 6 and in the ileum on day 14 of infection. Abnormalities of brush border function caused by infection correlated with the changes in microvillus surface area. In pair-fed animals on day 6, brush border surface area was slightly decreased in the ileum but increased in the jejunum, suggesting that the brush border injury resulted from infection rather than from malnutrition alone. The findings indicate that Y. enterocolitica inflicts a diffuse brush border injury that is in keeping with the generalized defect in brush border enzyme activity and transport function.     

Small bowel bypass prevents the trophic action of cholecystokinin on the rat pancreas

Summary The effect of a chronic administration of cholecystokinin (CCK) on the rat pancreas has been studied in rats subjected to a 90% jejunoileal bypass or an intestinal transection (controls). Jejunoileal bypass, when compared to transection, did not modify the size of the pancreas but decreased its enzyme content, especially for amylase, and reduced the number of zymogen granules. These structural and biochemical changes were maintained when bypassed animals were treated three times daily and for six days with cholecystokinin (20 Ivy Dog Units (IDU)/kg). In contrast, CCK treatment in transected animals induced growth of the pancreas due to cellular hypertrophy and hyperplasia; pancreatic enzyme content, especially for chymotrypsin, and the population of zymogen granules in acinar cells were also enhanced. It is concluded that jejunoileal bypass prevents the trophic action of chronic CCK on the pancreas. This work was presented in part at the XVI Meeting of the European Pancreatic Club, Cascais (Portugal), 13–15 September, 1984.