Endotoxemia inhibits intestinal adaptation in a rat model of short bowel syndrome

Sepsis is commonly associated with or complicates short bowel syndrome (SBS). The purpose of the present study was to investigate the effects of endotoxemia on intestinal adaptation in a rat model of SBS. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and re-anastomosis, SBS rats underwent 75% small bowel resection, and SBS-LPS rats underwent bowel resection and were given lipopolysaccharide. Bowel weight, organ weights, and parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height, and crypt depth) were determined on day 15 following operation. The results of this study demonstrate that SBS rats showed a significant increase (vs. Sham) in jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth. SBS-LPS animals demonstrated lower (vs. SBS rats) final body weight (215 +/- 7 vs. 287 +/- 10 g, P < 0.05), overall weight in duodenum (98+/- 2 vs. 119 +/-5 mg/cm, P < 0.05) and jejunum (144 +/- 9 vs. 189 +/- 16 mg/cm, P < 0.05), mucosal weight in jejunum (54 +/- 5 vs. 69 +/- 5 mg/cm, P < 0.05) and ileum (31 +/- 2 vs. 37 +/- 3 mg/cm, P < 0.05), mucosal DNA in jejunum (89 +/- 11 vs. 120 +/- 11 microg/cm, P < 0.05) and ileum (46 +/- 6 vs. 61 +/- 4 microg/cm, P < 0.05), jejunal crypt depth (152 +/- 19 vs. 189 +/- 12 microm, P < 0.05), and ileal villus height (405 +/- 63 vs. 515 +/- 30 pm, P < 0.05). In addition, the SBS group had no late (second week) mortality, whereas the SBS-LPS group had an 17% late mortality rate. In conclusion, in a rat model of SBS-LPS, endotoxemia appears to inhibit structural intestinal adaptation and increase mortality.     

Early ultrastructural adaptive changes of ileal enterocytes after proximal small bowel resection as determined morphometrically

The aim of the present study was to evaluate in terms of quantitative measurements whether the well-known histomorphological and functional adaptive changes in the intestinal mucosa after small bowel resection are accompanied by alterations on the ultrastructural level. Therefore, samples of the ileal remnants after a 60% proximal resection were processed for ultrastructural evaluation and analyzed employing point counting planimetry and direct measurements. Microvillus surface area increased from the bottom of the crypts to the villus tips in both resected and sham-operated animals. This increase in microvillus surface area from the crypt to the villus was significantly less pronounced after proximal resection, while there were no changes in the crypt compartment. No significant differences of the relative areas of the nuclei, mitochondria, and the rough endoplasmic reticulum were observed when comparing the different positions along the villus crypt axis in normal and hyperplastic mucosa. In agreement with functional and enzyme histochemical results, these ultrastructural findings provide further evidence for an altered pattern of enterocyte maturation after proximal resection, which is most probably due to an increase in the migration rate of the enterocytes.     

Intestinal development in the suckling rat: effect of insulin on the maturation of villus and crypt cell functions

The influence of insulin on the postnatal development of intestinal functions linked to villus cells (sucrase, lactase, maltase and aminopeptidase) and crypt cells (secretory component of immunoglobulins, SC) has been studied in suckling and weanling rats. At 9 days of age, the animals received a daily injection of insulin 12.5 mU g-1 body weight day-1 for 4 days. Compared with saline-treated controls, insulin had no effect on the development of the intestinal mucosal mass parameters determined in the jejunum, ileum and colon. A premature appearance of sucrase was noted in isolated jejunal villus and crypt cells, the level of activity reached by the enzyme being dependent of the amount of insulin injected. By 6 and 12 h after a single injection of the hormone (12.5 mU g-1 body weight), sucrase activity was detected in all the cell fractions along the villus-crypt axis. In villus cells of insulin-treated rats, maltase, lactase and aminopeptidase activities were significantly (P less than 0.001) increased (+201%, +50%, +207%, respectively, vs. controls), whereas the concentration of SC measured by a sensitive immunoradiometric assay was enhanced over the controls by 75% in villus cells, 83% in crypt cells and 172% in the liver. Weanling rats treated from day 10 to day 20 postpartum with 12.5 mU insulin also exhibited a higher intestinal production of SC (+93%, P less than 0.01) than did saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pituitary hormones and the small bowel: effect of hypophysectomy on intestinal adaptation to small bowel resection in the rat*

Abstract. The influence of pituitary hormones on intestinal adaptation to small bowel resection was studied by examining jejunal and ileal structure and function in control and in sham-operated rats, and in animals with 50% proximal or distal resection which were divided into three main groups: normally-fed, hypophysectomized, and pair-fed. The pituitary was removed 2 weeks before intestinal surgery and gut structure and function were studied 4 weeks later. The effectiveness of hypophysectomy was confirmed by histological examination of the aspirated pituitary, and by showing a significant subsequent reduction in weight of the testes and adrenals. Food intake and body weight fell significantly after removing the pituitary; intestinal surgery caused a transient further decrease in food intake. Measurements of intestinal villus height and crypt depth, indices of mucosal mass (mucosal wet weight, protein and DNA content/cm intestine), measurements of mucosal a-glucosidase activity, and in vivo galactose absorption/unit length of intestine all showed comparable results. In rats with an intact intestine, resection resulted in mucosal hyperplasia and increased segmental absorption. Following hypophysectomy, there was marked mucosal hypoplasia and hypofunction which seemed to be due largely to associated hypophagia since comparable changes were found in the pair-fed, sham-operated rats. However following pituitary removal, both distal jejunum and proximal ileum retained their capacity to regenerate though the magnitude of this adaptive change was much greater in the resected, pair-fed rats suggesting that hypophagia alone cannot explain the diminished adaptation to resection after hypophysectomy. By inference, pituitary hormones do influence the adaptive response to resection.     

Site of Substrate Stimulation of Jejunal Sucrase in the Rat

To identify the site of stimulation of sucrase by a sucrose diet, changes in sucrase-specific activity of jejunal mucosa were studied after introduction of sucrose diet to carbohydrate-deprived rats. Results were correlated with simultaneous changes in villus gradients of sucrase-specific activity. Simultaneous with the introduction of sucrose diet, [(3)H]thymidine (100 muCi) was administered intravenously, and rates of cell migration measured during adaptation to the new diet. After a 72-h fast, rats fed sucrose diet for 6, 12, or 18 h showed no change in sucrase-specific activity in either whole mucosa or villus gradients. However, within 18-24 h after starting a sucrose diet, there was a marked rise in whole mucosal sucrase-specific activity above fasting values (99 +/- 14 vs. 38 +/- 4 muM glucose/min per g protein, P < 0.001) in association with the development of a region of increased activity at the lower villus (154 +/- 22 vs. 60 +/- 9 muM glucose/min per g protein, P < 0.02, but with no change in villus tip activity (56 +/- 5 vs. 46 +/- 8 muM glucose/min per g protein). Similar changes were seen in animals fed 24 h of sucrose diet after a 72-h carbohydratefree diet. Fasted animals fed sucrose diet for 36 h had increased sucrase-specific activity at the villus tip (144 +/- 11 muM glucose/min per g protein) as well as at the lower villus region, and this pattern persisted at 1 wk of sucrose diet. Maximal activity patterns for isomaltase and maltase paralleled those for sucrase, but the villus gradients for lactase were unaffected by sucrose diet. The region of maximal sucrase-specific activity always coincided with or followed the leading edge of radioactivity as determined by liquid scintillation counting. Therefore, sucrose-mediated changes in sucrase activity of the jejunal mucosa in the rat appear to be initiated at the level of the crypt epithelial cell and are expressed after a latent period of 18-24 h during which these cells mature and migrate toward the villus tip.     

肠内肠外营养对大鼠肠道损伤后屏障功能恢复的实验研究

目的 比较肠内、肠外两种营养支持途径及不同营养物质对胃肠手术后大鼠肠屏障功能的恢复情况.方法 将40只雄性SD大鼠随机分为4组:空白对照组(C组)、肠外营养组(PN组)、普通肠内营养组(EN组)、富含谷氨酰胺的肠内营养组(G-EN组).PN组、EN组、G-EN组行盲肠切除+胃造口置管手术并联合使用阿莫西林50 mg+甲硝唑20 g两次进行干预.术后第1天起各组等氮等热卡连续给予营养支持7 d,于末段回肠5 cm处取肠段1 cm,在光镜下观察肠黏膜形态;采用酶联免疫吸附实验(ELISA)比较血浆D-乳酸含量,检测肠道黏膜通透性;双抗体夹心ABC-ELISA法检测肿瘤坏死因子水平(TNF-α);免疫组化法观察肠黏膜occludin蛋白表达.结果 PN组肠黏膜明显萎缩,其绒毛高度、黏膜厚度、隐窝深度、绒毛表面积及肠黏膜occludin蛋白表达均显著低于C组、EN组、G-EN组(P<0.05),D-乳酸及TNF-α水平显著高于C组、EN组、G-EN组(P<0.05);EN组肠黏膜萎缩较明显,其肠黏膜形态及肠黏膜occludin蛋白表达均低 于C组、G-EN组(P<0.05),D-乳酸及TNF-α水平显著高于C组及G-EN组(P<0.05);G-EN组肠道形态、肠黏膜occludin蛋白表达、D-乳酸及TNF-α水平与C组无统计学差异(P>0.05).结论 谷氨酰胺强化的肠内营养在维护肠黏膜屏障功能、减轻炎症反应,增加肠上皮occludin蛋白表达等方面优于单独使用肠内营养液或肠外营养液,更有助于胃肠手术后大鼠肠屏障功能的恢复.     

Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport.

To better understand the pathogenesis of infantile viral gastroenteritis, we studied Na+ and Cl- fluxes in vitro in short-circuited jejunal epithelium from 8-10-day-old piglets after infection with a standard dose of human rotavirus given via nasogastric tube. 11 infected piglets, all of whom became ill, were compared with 9 uninfected, healthy litter-mates. When killed 72 h after infection, intestinal villi were shorter and crypts deeper (P less than 0.025) in duodenum, upper jejunum, and mid-small intestine, but not ileum in infected piglets. Virus antigen was seen by fluorescence microscopy in occasional jejunal villus tip cells in only four infected piglets and no controls at 72 h. Net Na+ and Cl- fluxes did not differ from noninfected litter-mate controls under basal conditions, but response to glucose was blunted in infected piglets (P less than 0.001). Theophylline stimulated net Cl- secretion in both infected and control animals, and cyclic AMP concentration in isolated jejunal villus enterocytes did not differ significantly. In isolated jejunal villus enterocytes of infected piglets, thymidine kinase activity increased (P less than 0.001), and sucrase activity decreased (P less than 0.001). We conclude that in this invasive enteritis caused by a major human viral pathogen, glucose-coupled Na+ transport is impaired in the jejunum at a time when the villus epithelium shows enzyme characteristics of crypt epithelium, and when little or no virus is present. These findings are identical to those occurring in an invasive coronavirus enteritis of piglets but differ markedly from those seen with enterotoxigenic diarrhea.     

Alterations of intestinal membrane-bound enzymes in three types of hypertensive rats

Alkaline phosphatase, sucrase, Na+,K+-ATPase and Mg2+-ATPase specific activities of crude membrane fractions, prepared from duodenal, jejunal, ileal and colonic mucosa, have been estimated in three types of hypertensive rats: the spontaneously hypertensive rat (SHR), the DOCA-saline treated rat and the renovascular rat (Goldblatt one-kidney, one-clip rat; 1K-1C). Alkaline phosphatase and sucrase specific activities have been measured in purified jejunal brush-border membranes. When compared with its normotensive age-matched control (WKY rat), the SHR has a lower activity of alkaline phosphatase in duodenal and jejunal crude membrane fractions, whereas a higher activity in colonic Na+,K+-ATPase is recorded. In purified jejunal brush-border membranes, lower alkaline phosphatase activity and higher sucrase activity were found. These differences occur in the young prehypertensive SHR as well as in the adult animal. In the DOCA-treated rat, the only significant alteration in crude membrane fractions is a decreased Mg2+-ATPase activity at all regions of intestinal mucosa. In purified jejunal brush-border membranes both alkaline phosphatase and sucrase activities are increased at 4 or 7 weeks but especially at 13 weeks of hypertension. In the 1K-1C rat, no significant modification appears in crude membrane fractions or in purified jejunal brush-border membranes, but a decrease in alkaline phosphatase and in sucrase activities is probable after 13 weeks of hypertension. Since alterations of the intestinal enzymes are different in the three types of hypertensive rats it is concluded that the changes are not secondary to the hypertension condition. In the SHR, these alterations are present in the young prehypertensive animal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of differing purified cellulose, pectin and hemicellulose fiber diets on mucosal morphology in the rat small and large intestine

The effects of increasing amounts of differing single-fiber sources in chemically-defined and nutritionally-equivalent diets on morphometric measurements of the rat small and large intestinal mucosa were examined. Male Wistar rats received a fiber-free diet, or diets containing 4.5% or 9.0% cellulose, pectin, or hemicellulose. Cellulose and pectin increased jejunal (but not ileal) villus and crypt heights, whereas hemicellulose increased ileal (but not jejunal) mucosal height. Moreover, cellulose and pectin (but not hemicellulose) increased crypt heights in cecum and proximal (but not distal) colon. Parallel increases in the mitotic index were seen with cellulose and pectin diets, but there was a decrease with hemicellulose, suggesting different mechanisms for altered patterns of cell renewal induced by orally-administered single-fiber sources. These changes indicate that differing single-fiber sources exert differential structural effects along the length of the small and large intestine in the rat.     

Inhibition of intestinal epithelial DNA synthesis and adaptive hyperplasia after jejunectomy in the rat by suppression of polyamine biosynthesis

Transient increases in the activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine biosynthesis, may be critical to initiation of cell growth. We previously reported such increases in ODC activity, and the polyamines, putrescine, and spermidine in rat ileal mucosa between days 1 and 4 after intestinal resection. During this time, there is initiation of mucosal cell hyperplasia, as measured morphologically and biochemically. Intestinal weight and mucosal thickness increase, as do mucosal DNA content and DNA synthesis. In the present study, we gave rats the specific irreversible ODC inhibitor, alpha-difluoromethyl ornithine (DFMO), beginning 3 d before jejunectomy. DFMO completely suppressed the increases in ODC activity and polyamine content in the intestinal mucosa. The suppression in ODC activity was associated with an 87% suppression of DNA synthesis, and resulted in a complete abolition of intestinal adaptation, as manifested by the absence of intestinal weight gain, increase in mucosal thickness, or increase in crypt cell production. Our results indicate that the increases in ODC activity and polyamine biosynthesis are critical for adaptive postresectional crypt cell proliferation in vivo, and that the critical step mediated by polyamines in this adaptive process is the onset of new DNA synthesis.     

Clinical studies of intestinal folate conjugases

Clinical differences between the two human intestinal mucosal folate conjugases were assessed by measurement of their activities in normal individuals and in patients with chronic diarrhea of differing causes. Intracellular folate conjugase (ICFC) was 15-fold more active than brush border folate conjugase (BBFC) in jejunal mucosa from seven obese patients undergoing elective gastric bypass surgery. The activity of ICFC was similar among normal volunteers and patients with diarrhea of unknown origin (DUO), gluten-sensitive enteropathy (GSE), inflammatory bowel disease (IBD), and the short bowel syndrome (IBD-SBS). By contrast, BBFC, sucrase, and lactase were decreased significantly in GSE, and BBFC was increased in IBD-SBS. The activity of BBFC correlated with lactase and with sucrase in the normal subjects and in patients with DUO, whereas no correlations were found with the activity of ICFC in any group. Our clinical studies confirm that ICFC and BBFC are different enzymes. ICFC is not affected by intestinal disease, whereas the activity of jejunal BBFC, like that of other brush border enzymes, is decreased by mucosal injury and is also capable of adapting to distal small intestinal disease or surgical resection.     

Pathogenesis of Shigella diarrhea. XVI. Selective targetting of Shiga toxin to villus cells of rabbit jejunum explains the effect of the toxin on intestinal electrolyte transport.

To examine the mechanism by which Shiga toxin alters intestinal water and electrolyte transport, ligated loops of rabbit jejunum were incubated in vivo with purified toxin and then studied in vivo by single pass perfusion and in vitro by the Ussing chamber voltage-clamp technique. Toxin exposure led to accumulation of water in the jejunal lumen, associated with decreased active basal NaCl absorption. Glucose- and alanine-stimulated Na absorption were also reduced, while toxin had no effect on either basal short-circuit current or the secretory response to theophylline. These observations suggest that Shiga toxin selectively inhibits NaCl absorption without significantly altering active anion secretion. To localize the cellular site of toxin action, populations of villus and crypt cells from rabbit jejunum were isolated and studied. Villus cells had a greater content of the glycolipid Shiga toxin receptor, Gb3, had more toxin binding sites than did crypt cells, and were much more sensitive than crypt cells to toxin-induced inhibition of protein synthesis. These experiments demonstrate that purified Shiga toxin inhibits jejunal fluid absorption without affecting active fluid secretion by a preferential effect on villus cells. The results suggest that this is due to the differential distribution of toxin receptors on villus compared to crypt cells.     

肢体缺血再灌流致肠损伤的组织学观察

目的 :通过动物实验观察肢体缺血再灌流损伤对肠粘膜形态学结构的影响。方法 :110只Wistar大鼠随机分成三个组 :缺血 2h ,缺血 3h和对照组。缺血、再灌注 1、 2、 3和2 4h取材行光镜观察和组织学评估。结果 :肢体缺血和再灌流期间 ,大肠和小肠粘膜固有层毛细血管扩张、充血、多核白细胞浸润 ,粘膜厚度和隐窝深度明显减少 (P <0 0 1)。小肠绒毛高度相对增加 ,隐窝细胞变性、坏死。结论 :肢体缺血再灌流可引起肠结构和功能改变     

Intestinal infection with Nematospiroides dubius selectively increases lactase expression by mouse jejunal enterocytes

1. Intestinal structure, lactase (beta-galactosidase; EC 3.2.1.23) activity and alkaline phosphatase activity have been determined in mouse jejunal and ileal tissues before and during infection with the intestinal parasite Nematospiroides dubius. 2. Oral infection with small numbers of N. dubius larvae caused villus height, crypt depth and enterocyte migration rate to increase in the mouse jejunum. None of these effects occurred in ileal tissue. 3. Lactase activity also increased in jejunal, but not ileal, tissue of infected mice. This increase was associated with a doubling of the rate at which activity appeared in the brush-border membrane of enterocytes during migration over the basal regions of jejunal villi. Alkaline phosphatase activity in jejunal tissue remained unchanged in infected mice. 4. Attention is drawn to the fact that this is the first occasion when crypt cell hyperplasia has been found to be positively correlated with an increase in lactase activity and a decrease in cytotoxic/suppressor T-cells. Further work is needed to establish the primary cause of these effects.     

Fat-stimulated cholecystokinin release following transplantation of the entire small bowel or of different intestinal segments in rats

This study presents data on the fat-stimulated release of cholecystokinin (CCK) in conscious rats 11 and 84 days after one-stage transplantation of the entire small bowel, or of jejunal, jejunoileal, or ileal segments, under syngeneic and allogeneic conditions. After allotransplantation, ciclosporin (CsA) was administered for graft acceptance. The results were compared with those in unoperated controls and in animals that had undergone small-bowel resections leaving jejunal, jejunoileal, or ileal remnants. When the entire small bowel was grafted under syngeneic (92.5±8.3; 106.6±7.5) or allogeneic (110.5±5.5.; 101.2±6.9) conditions, CCK release (pg/ml per 60 min) was similar (P>0.05) to that of the controls (110.3±9.0; 94.7±6.8) at both measurement points. Recipients of jejunal or ileal segmental isografts showed a significantly elevated (P<0.05) output of CCK (jejunal graft: 176.4±18.5; 125.5±10.1—ileal graft: 55.9±9.0; 30.1±5.4) compared with corresponding small-bowel resections (jejunal remnant: 69.0±7.9; 93.5±3.9—ileal remnant: 16.7±3.7; 6.6±1.3). In contrast the difference was not significant (P>0.05) when jejunoileal segments were grafted (jejunoileal graft: 74.4±19.6; 47.0±10.4—jejunoileal remnant: 50.7±11.0; 47.0±11.9). All recipients of jejunal allografts died between day 8 and day 10 after transplantation, due to functional impairment. Two-stage segmental jejunal allotransplantation, with insertion of the graft into the continuation of the gastrointestinal tract in an accessory, non-functional position after 28 days was successful. Due to this technique, we could gather data on day 84. Recipients of jejunal (118.2±7.6), jejunoileal (87.1±19.7; 48.6±9.3), or ileal (48.1±6.7; 21.6±4.6) allografts showed no significant (P>0.05) differences in CCK output compared with isografts, either on day 11 or on day 84. Our data indicate that transplantation of the entire small bowel affects the fat-stimulated CCK release neither in the early postoperative period nor 3 months after transplantation. In contrast, transplantation of jejunal or ileal segmental isografts caused a significantly elevated output of CCK compared with corresponding resection remnants. Immunosuppression with CsA did not affect CCK release after transplantation, but led to functional impairment with fatal outcome when a short jejunal segment was grafted. This could be prevented by applying the two-stage technique.     

5-Oxo-6,8,11,14-eicosatetraenoic acid stimulates isotonic volume reduction of guinea pig jejunal crypt epithelial cells.

5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a recently discovered arachidonate metabolite that is a potent activator of eosinophils and neutrophils and may be an important mediator of inflammation. The objective of the present investigation was to determine whether 5-oxo-ETE affects the isotonic volume of Cl(-) secretory intestinal crypt epithelial cells. 5-Oxo-ETE caused rapid shrinkage of guinea pig jejunal crypt epithelial cells to a reduced but stable volume, which was measured electronically. This effect was prevented by Cl(-) and K(+) channel blockers and inhibitors of protein kinase C. 5-Oxo-ETE (EC(50) = 20 pM) was more potent than any of the other agonists tested, including its precursor, 5-hydroxy-6,8,11,14-eicosatetraenoic acid (EC(50) = 5 nM); leukotriene D(4) (EC(50) = 1 nM); vasoactive intestinal peptide (EC(50) = 200 pM); and bradykinin (EC(50) = 50 nM). Leukotriene B(4) had no effect on crypt cell volume. In contrast to its effects on crypt cells, 5-oxo-ETE had no effect on the volume of jejunal villus cells. These results indicate that 5-oxo-ETE induces an isotonic volume reduction in intestinal crypt epithelial cells that appears to be dependent on Cl(-) secretion and activation of protein kinase C.     

Structural and functional evolution of jejunal allograft rejection in rats and the ameliorating effects of cyclosporine therapy.

We assessed the structural and functional evolution of small intestinal transplant rejection in a rat model by use of 1-micron section, electron microscopic, and in vitro electrophysiologic techniques to study jejunal mucosa 3, 6, and 9 d posttransplantation. The earliest structural abnormalities detected in jejunal loops transplanted from Lewis X Brown Norway F1 hybrids into Lewis rats occurred within 3 d posttransplantation and consisted of focal endothelial cell injury of the microvasculature and focal injury of crypt epithelial cells. Both alterations were associated with adjacent infiltration of large lymphoid cells, and both markedly progressed and became rather diffuse over the following 6 d. In contrast, villus absorptive cells were not markedly altered in structure until the 9th postoperative day. As compared with host jejuna, allograft jejunal epithelium demonstrated multiple functional abnormalities. Transepithelial resistance declined progressively by days 6 and 9 (both P less than 0.05), although baseline transepithelial spontaneous potential difference was only affected at day 9 (P less than 0.01). Stimulated absorption by allograft jejuna, as assessed by measuring electrical response to mucosal glucose, was not significantly diminished until day 9 (P less than 0.05). In contrast, stimulated secretion assessed by measurement of electrical response to serosal theophylline was diminished by day 6 (P less than .01). These data suggest that the earliest epithelial injury during rejection, as judged both structurally and functionally, occurs in the crypt and is paralleled by endothelial injury at the level of the microvasculature. Thus, the primary targets for rejection are most likely endothelial cells and crypt epithelial cells. In contrast, structural and functional impairment of villus epithelium is detectable only at substantially later times during rejection and are most likely secondary processes related to either ischemia produced by microvascular injury or decreased epithelial regenerative ability secondary to crypt injury. Last, we show that the detrimental structural and functional sequellae of jejunal transplantation across the major histocompatibility complex in this model is strikingly ameliorated with cyclosporine therapy.     

Structural and functional alterations in the mucosa of self-filling intestinal blind loops in rats.

1. Self-filling blind loops of jejunum were constructed in three groups of rats; in the first, blind loops were created without further manipulation; in the second the bile was diverted permanently into the lower ileum below the blind loop, whereas in a third neomycin was added to the drinking water throughout the experiment. Two weeks after the creation of the blind loops, they were used for structural and functional studies. 2. Morphometric and microdissection techniques demonstrated that the surface area of the individual villi of the mucosa of 'ordinary' blind loops had increased fourfold in comparison with corresponding control jejunum, whereas the increase was only twofold in rats with bile diversion or in the series treated with neomycin. There were proportional increases in crypt length and mitotoic activity of the crypts in all three series, which suggest that the alterations in the mucosa were due to hyperplasia in both villus and crypt compartments. 3. Sucrase, succinate dehydrogenase, alkaline phosphatase and non-specific esterase activities, determined biochemically or histochemically, were reduced in the mucosae of all blind loops, though the changes were most pronounced in the 'ordinary' blind loops. The accumulation of L-phenylalanine by mucosal slices in vitro was depressed, although the decrease was less marked in the series treated with neomycin. 4. These results suggest that both bacteria and deconjugated bile acids play a role in the development of the hyperplastic changes of the blind-loop mucosa, but that another factor might also be involved: as a possible candidate, stasis of the intestinal contents was considered. 5. To test this hypothesis, loops of rat colon were transposed into the jejunum. Above the transposed loop, the jejunal mucosa developed hyperplasia of both villus and crypt compartments, with a reduction in its ability to accumulate L-phenylalanine. It is argued that these changes, probably caused by stasis of the intestinal contents, are triggered off by the dilatation of the gut, which may also be implicated in the mucosal alterations in blind loops.     

Dietary fat selectively alters transport properties of rat jejunum.

The influence of dietary fatty acid composition on intestinal active and passive transport function, brush border membrane composition, and morphology was examined in rats. Animals fed a semisynthetic diet high in saturated fatty acids demonstrated enhanced in vitro jejunal uptake of decanoic, dodecanoic, palmitic, stearic, and linoleic acid, as well as cholesterol and chenodeoxycholic and taurochenodeoxycholic acid, as compared with uptake in animals fed a semisynthetic diet high in polyunsaturated fatty acids but equivalent in total content of fat and other nutrients, or as compared with Purina chow. Feeding the saturated fatty acid diet was also associated with reduced jejunal uptake of a range of concentrations of glucose, enhanced ileal uptake of leucine, unchanged uptake of galactose, and lower uptake of decanol. The semisynthetic diets did not alter brush border membrane protein, sucrase or alkaline phosphatase activities, cholesterol, or total phospholipids, although the percentage of jejunal amine phospholipids was higher than in rats fed chow. The morphologic differences between the jejunum and ileum were abolished in animals fed the high polyunsaturated fatty acid diet; in rats fed the high saturated fatty acid diet, there was reduced mean ileal villus height, width, thickness, surface area, cell size, and villus density, as well as reduced mucosal surface area. The changes in jejunal transport were not correlated with the alterations in morphology, unstirred layer resistance, food intake, or body weight gain. It is proposed that small changes in the percentage of total dietary lipids composed of essential and nonessential fatty acids (without concurrent alterations in dietary total fat, carbohydrate, or protein) influence active and passive intestinal transport processes in the rat.     

Effect of moderate prolonged ethanol ingestion on intestinal disaccharidase activity and histology

A previous study has shown that long-term feeding of ethanol in high doses (36% of total calories) causes marked changes in intestinal mucosal disaccharidase activity as well as blunting of the intestinal villi. To determine whether similar damage occurs in response to a more moderate ethanol exposure, we pair fed rats a liquid diet that provided 15.5% of total calories from ethanol for 5 weeks. In the proximal segment of the intestine, we found that ethanol did not affect the total activities of maltase (8.0 +/- 2.4 U vs. control value of 6.7 +/- 1.8 U), sucrase (1.5 +/- 0.5 U vs. control of 1.2 +/- 0.3 U), or lactase (125 +/- 42 mU vs. control of 107 +/- 36 mU). Similarly, we found no differences from control values for the three disaccharidases in the middle or distal small bowel. The mucosal protein content of the experimental animals did not differ from values found in the control animals. In addition, no change in intestinal villus height or crypt depth was detected. The zinc content of hair and serum was not affected by the ethanol feeding. We conclude that prolonged ingestion of a moderate dose of ethanol does not damage the small intestinal disaccharidase enzymes, mucosal protein content, or intestinal architecture.