Search

Background: The microbiome of the gastrointestinal tract is a vast collection of microorganisms implicated in numerous aspects of normal physiology and disease pathogenesis. The use of gnotobiotic mouse models, with single or specific communities of microbes comprising the microbiome, can enhance our understanding of the microbiome-host relationship. We hypothesized that gnotobiotic mice would exhibit differences in mucosal homeostasis when compared with mice with conventional flora (CF)., Materials and Methods: Single-organism gnotobiotic mice were generated containing Escherichia coli MG1655, Akkermansia muciniphila, Bacteroides eggerthii, and Clostridium symbiosum, representing four of the major phyla present in the gastrointestinal tract. Distal ileal segments were harvested from adult mice, and histologic sections were H&E stained and used to measure villus height and crypt depth. Immunohistochemistry was performed with Ki67 and TUNEL as markers of proliferation and apoptosis, respectively., Results: When compared to the ileum from CF mice, the ileum from all groups of gnotobiotic mice had significant increases in nearly all measured parameters. In addition, significant differences were seen among certain gnotobiotic groups for villus height, crypt depth, and apoptosis., Conclusions: Single-organism gnotobiotic mice demonstrate enhanced morphometric parameters compared with mice with CF and show differences in growth patterns among bacterial species. These findings suggest unique interactions between individual bacteria and the host animal which hold potential for future therapeutic strategies aimed at mucosal restoration. The mechanisms involved in this process therefore warrant further study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We investigated the passive mechanical properties of villi in ex vivo preparations of sections of the wall of the distal ileum from the brushtail possum (Trichosurus vulpecula) by using a flow cell to impose physiological and supra-physiological levels of shear stress on the tips of villi. We directly determined the stress applied from the magnitude of the local velocities in the stress inducing flow and additionally mapped the patterns of flow around isolated villi by tracking the trajectories of introduced 3 µm microbeads with bright field micro particle image velocimetry (mPIV). Ileal villi were relatively rigid along their entire length (mean 550 µm), and exhibited no noticeable bending even at flow rates that exceeded calculated normal physiological shear stress (>0.5 mPa). However, movement of villus tips indicated that the whole rigid structure of a villus could pivot about the base, likely from laxity at the point of union of the villous shaft with the underlying mucosa. Flow moved upward toward the tip on the upper portions of isolated villi on the surface facing the flow and downward toward the base on the downstream surface. The fluid in sites at distances greater than 150 µm below the villous tips was virtually stagnant indicating that significant convective mixing in the lower intervillous spaces was unlikely. Together the findings indicate that mixing and absorption is likely to be confined to the tips of villi under conditions where the villi and intestinal wall are immobile and is unlikely to be greatly augmented by passive bending of the shafts of villi.

Background: With increase in the incidence of resistance to antibiotics, probiotics are emerging as a promising adjunctive periodontal therapy. The authors of this study evaluate the influence of probiotic (PROB) supplementation on ligature-induced periodontitis (LIP) and intestinal morphology in rats., Methods: Thirty-two rats were randomly divided into four groups: control (C), LIP, PROB, and LIP/PROB. In groups PROB and LIP/PROB, the PROB was administered orally by addition to the drinking water of the animals for 44 days. In groups LIP and LIP/PROB, the mandibular right first molar of the animals received a cotton ligature that was left in the same position for 14 days. All animals were euthanized 44 days after the start of the PROB supplementation. The jaws were resected and histomorphometric analyses were performed. The measurements included evaluation of attachment loss (AL) and alveolar bone level (ABL) on the distal root of the mandibular first molar. Samples of the duodenum, jejunum, and ileum were also dissected from each animal to evaluate the villous height (VH) and crypt depth (CD). The data obtained were subjected to statistical analyses (analysis of variance, Tukey; P <0.05)., Results: Mean values of AL and ABL were significantly higher in group LIP compared with group LIP/PROB (AL: 3.05 ± 0.57 mm and 1.78 ± 0.63 mm, respectively; ABL: 4.21 ± 0.42 mm and 3.38 ± 0.17 mm, respectively). In group LIP/PROB, the mean values of VH and CD of the jejunum were significantly higher than the ones from group LIP (VH: 672.1 ± 83.3 µm and 528.0 ± 51.7 µm, respectively; CD: 463.8 ± 100.9 µm and 269.0 ± 48.4 µm, respectively)., Conclusions: It can be concluded that PROB supplementation 1) reduces AL and alveolar bone loss in rats with LIP and 2) can protect the small intestine from reactive changes induced by LIP.

Nitric oxide (NO) donors increase the permeability of water-soluble compounds with neither loss of cell viability nor lactate dehydrogenase release. In addition, the rectal absorption of insulin has been reported to be remarkably enhanced in the presence of NO donors such as 1-Hydroxy-3-(3-aminopropyl)-3-isopropyltriazene 2-oxide (NOC5) and N-Ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino) ethanamine (NOC12). In this study, we examined the effect of sodium nitroprusside (SNP), which is used in clinical situations as a vasodilator, as a model NO donor on the ileal mucosa of rats. We used an in situ closed loop method in rat ileum to study changes in the permeability of fluorescein isothiocyanate dextran 4000 (FD-4) as a paracellular marker. The effect of SNP (1 and 10mg/kg) on the protein expression level of the claudin family was examined by Western blotting. The membrane permeation of FD-4 was increased but no mucosal lesion was observed upon the administration of SNP. Moreover, the protein expression level of the claudin family was not changed by the administration of SNP. When SNP was removed 2h after its administration, no significant change in the membrane permeation of FD-4 was observed. Moreover, no decrease of ileal membrane resistance or disruption of membrane structure was observed. The absorption-enhancing effect of SNP was associated with low injury and low toxicity. The reversibility of the effect of SNP was observed. Consequently, it was shown that SNP can be a useful absorption enhancer., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The colon mucus layers minimize the contact between the luminal flora and the epithelial cells, and defects in this barrier may lead to colonic inflammation. We now describe an ex vivo method for analysis of mucus properties in human colon and mouse small and large intestine. Intestinal explants were mounted in horizontal perfusion chambers. The mucus surface was visualized by adding charcoal particles on the apical side, and mucus thickness was measured using a micropipette. Mucus thickness, adhesion, and growth rate were recorded for 1 h. In mouse and human colon, the ability of the mucus to act as a barrier to beads the size of bacteria was also evaluated. Tissue viability was monitored by transepithelial potential difference. In mouse ileum, the mucus could be removed by gentle aspiration, whereas in colon ∼40 μm of the mucus remained attached to the epithelial surface. Both mouse and human colon had an inner mucus layer that was not penetrated by the fluorescent beads. Spontaneous mucus growth was observed in human (240 μm/h) and mouse (100 μm/h) colon but not in mouse ileum. In contrast, stimulation with carbachol induced a higher mucus secretion in ileum than colon (mouse ileum: Δ200 μm, mouse colon: Δ130 μm, human colon: Δ140 μm). In conclusion, while retaining key properties from the mucus system in vivo, this setup also allows for studies of the highly dynamic mucus system under well-controlled conditions.

To demonstrate the relationship between intestinal histology and function, we investigated the possibility that compensatory enlargement of villi in the chickens' remnant intestine can be induced after 50% or 80% jejunal resection as well as after 50% jejunal plus 70% ileal resection. Compared with intact control chickens, operated chickens showed an almost similar body weight, nitrogen retention, and ether extract digestibility, an improved dry matter digestibility, and a much greater absorption of protein and ether extract by the remnant jejunum and ileum. This suggests an enhanced absorptive function of the remnant intestine. In these chickens, increased value of most light microscopic parameters, increased frequency of anastomosing of each villus, and increased number of protuberated epithelial cells appeared with an increase in the intestinal resection area. This suggests that intestinal villi and epithelial cells are hypertrophied in the remnant jejunum and ileum, and that intestinal villi adapt to activated intestinal absorptive function not by increasing their numbers, but by fusing together into larger villi. These findings demonstrate that intestinal histology is intimately related to intestinal function.

Small intestine mucosa is often affected with malabsorptive, autoimmune and inflammatory pathological processes. However, morphometric data on the healthy human small intestine mucosa, especially ileum, are scarce. We aimed to obtain histoquantitative data on the healthy jejunal and ileal mucosa and assess the effects of gender and ageing on these parameters. Computer-aided morphometric analysis was performed on 24 jejunal and 25 ileal biopsy samples collected upon routine endoscopy screening of healthy persons with a family history of intestinal malignancy. Subjects were distributed in four groups according to age and sex: adult (<60 years) and elderly (>60 years) males, and adult (<60 years) and elderly (>60 years) females. Results were statistically analyzed with Mann-Whitney U test. Jejunal mucosal thickness was significantly reduced in elderly subjects (p<0.05), especially in elderly females compared to adult ones (p<0.05). Jejunal villi were significantly wider in adult than in the elderly subjects (p<0.05), whereas ileal villi were significantly wider in elderly compared to adult subjects (p<0.01) and in male compared to female subjects (p<0.05). No statistically significant differences were found in other histoquantitative parameters (mucosa epithelium height, crypt numerical density, villous height, crypts and villous perimeter, diameter and epithelium height) of jejunal and ileal mucosa. This study provides complete morphometric data on the healthy human jejunum and the first relevant data on the healthy ileal mucosa, thus representing a valuable morphometric reference for future histoquantitative studies of human small bowel mucosa in both healthy and disease affected individuals.

Background: Ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC) and for familial adenomatous polyposis (FAP) with many rectal polyps. Pouchitis is one of the more frequent complications after IPAA in UC patients; however, it is rare in FAP., Objective: Evaluate pro-apoptotic activity in endoscopically and histological normal mucosa of the ileal pouch in patients with UC and FAP., Methods: Eighteen patients (nine with UC and nine with FAP) with J pouch after total rectocolectomy were studied. Biopsies were obtained from the mucosa of the pouch and from normal ileum. The specimens were snap-frozen and the expressions of Bax and Bcl-2 were determined by immunoblot of protein extracts and by immunohistochemistry analysis. FADD, Caspase-8, APAF-1 and Caspase-9 were evaluated by immunoprecipitation and immunoblot., Results: Patients with UC had significantly higher protein levels of Bax and APAF-1, Caspase-9 than patients with FAP, but were similar to controls. The expressions of Bcl-2 and FADD, Caspase-8 were similar in the groups. Immunohistochemistry for Bax showed less intensity of immunoreactions in FAP than in UC and Controls. Bcl-2 immunostaining was similar among the groups., Conclusion: Patients with FAP present lower levels of pro-apoptotic proteins in all methods applied, even in the absence of clinical and endoscopic pouchitis and dysplasia in the histological analysis. These findings may explain a tendency of up-regulation of apoptosis in UC patients, resulting in higher rates of progression to pouchitis in these patients, which could correlate with mucosal atrophy that occurs in inflamed tissue. However, FAP patients had low pro-apoptotic activity in the mucosa, and it could explain the tendency to low cell turn over and presence of adenomas in this syndrome.

In experiments on rats we studied reabsorption and secretory activity of the mucosa in isolated segments of the ileum and sigmoid colon used for urinary bladder intestinoplasty after cystectomy. Ileal mucosa was found to retain high metabolic activity under changed conditions. It reabsorbs urea, creatinine, potassium, sodium, chlorine, phosphorus, calcium, glucose, and uric acid from the urine and secretes magnesium, iron, and proteins into the urine. Sigmoid mucosa appeared to be less active in terms of reabsorption of the studied urine metabolites, but more actively secreted calcium and magnesium into urine and additionally secreted sodium. It was accompanied by an increase in blood concentrations of urea, creatinine, glucose, phosphorus, magnesium (only for sigmoid colon) and development of hypoproteinemia. These findings are important for investigation and prevention of metabolic complications after urinary bladder intestinoplasty.

Background & Objective: Agents that increase the permeability of intestinal epithelium promote the absorption of nutrients by the gut. High calcium concentration in the gut has been shown to enhance passive transport of glucose in the rat intestine. An increase in the permeability of the intestinal epithelium may account for this observation. The present study was aimed at monitoring the permeability of intestine of rats fed high or low calcium diets., Methods: Everted intestinal sacs were used to study transports of substances across the gut. While radioactive and non radioactive calcium isotopes were employed to study the active transport and passive transport of calcium, transport of labelled mannitol was taken as a measure of passive permeability., Results: High calcium diet increased the passive transport of mannitol and calcium while decreasing the active transport of calcium by the everted gut sacs., Interpretation & Conclusion: Passive mechanisms are enhanced by high calcium diet, while low calcium diet favours active transport. Calcium in the diet may be affecting intestinal transport.

The objective of this work was to evaluate the effect of the ascorbic acid supplementation on the cellular proliferation on the ileum mucosa of diabetic rats. Fifteen 90-days rats were divided in the groups: control, diabetic and diabetic supplemented with ascorbic acid (DA). Two hours prior the sacrifice, they were injected with Vincristin. Semi-seriate histological cuts stained with HE were accomplished. About 2500 crypt cells from the intestinal mucosa were counted in order to obtain the metaphasic indexes. The height and depth of 30 villi and 30 crypts were measured for each animal, respectively. The metaphasic indexes showed no significant changes when we compared the three groups: 20.2 +/- 0.7 (control), 18 +/- 1.9 (diabetic) and 17 +/- 1.4 (DA) (p > 0.05). The values obtained from the crypts measurement were 221.2 +/- 8.5 (control), 225.3 +/- 9.5 (diabetic) and 222 +/- 34 (DA). The villi of the control, diabetic and DA animals presented the following results: 301.7 +/- 25.33, 304.8 +/- 25.63 and 322.1 +/- 45.77 respectively. The morphometric data were not different statistically (p > 0.05). Summing up, the present work showed that there was no alteration in the cellular proliferation of the ileum of diabetic-induced rats supplemented with ascorbic acid.

The objective of this experiment was to evaluate the influence of Gln and vitamin E (VE) supplementation in the diet of broiler chickens (Cobb-Vantress) on the morphometry of the intestinal mucosa. The design was completely randomized in a 2 x 3 (VE x periods of administering Gln) factorial arrangement. The levels of VE used were 10 and 500 mg/kg of diet and 3 periods of administering (1%) Gln-supplemented starter diet (for the first 7 or 14 d of life or for no added Gln), totaling 6 treatments with 5 replicates of 50 birds per experimental unit. In the growth period (d 22 to 41 posthatch), the treatments consisted only in the respective levels of VE. On d 7, 14, 21, and 41 posthatch, 2 birds per replicate were killed, and samples of the duodenum, jejunum, and ileum were subsequently removed, fixed in Bouin solution, and later embedded in paraffin and stained with hematoxylin-eosin. The parameters analyzed were villus height and crypt depth. An ANOVA was applied to the obtained data, and the means were compared using Tukey's test (5% significance level). Greater development was observed in the duodenum, followed by the jejunum and ileum. On 41 d of life, diets with 10 mg of VE/kg supplemented with Gln (for the first 7 d of life) provided better development of the intestinal mucosa in broiler chickens.

Following massive small bowel resection (SBR) in mice, there are sustained increases in crypt depth and villus height, resulting in enhanced mucosal surface area. The early mechanisms responsible for resetting and sustaining this increase are presently not understood. We hypothesized that expansion of secretory lineages is an early and sustained component of the adaptive response. This was assessed in the ileum by quantitative morphometry at 12 h, 36 h, 7 days, and 28 days and by quantitative RT-PCR of marker mRNAs for proliferation and differentiated goblet, Paneth cell, and enterocyte genes at 12 h after 50% SBR or sham operation. As predicted, SBR elicited increases of both crypt and villus epithelial cells, which were sustained though the 28 days of the experiment. Significant increases in the overall number and percentage of both Paneth and goblet cells within intestinal epithelium occurred by 12 h and were sustained up to 28 days after SBR. The increases of goblet cells after SBR were initially observed within villi at 12 h, with marked increases occurring in crypts at 36 h and 7 days. Consistent with this finding, qRT-PCR demonstrated significant increases in the expression of mRNAs associated with proliferation (c-myc) and differentiated goblet cells (Tff3, Muc2) and Paneth cells (lysozyme), whereas mRNA associated with differentiated enterocytes (sucrase-isomaltase) remained unchanged. From these data, we speculate that early expansion of intestinal secretory lineages within the epithelium of the ileum occurs following SBR, possibly serving to amplify the signal responsible for initiating and sustaining intestinal adaptation.

Our previous studies demonstrated that sodium glucose cotransporter 1 (SGLT-1) was induced in the remnant ileum of total colectomized rats via the action of factors other than hyperaldosteronism. The aim of the present study was to clarify whether fecal stream is required for the enhancement of SGLT-1-mediated sodium transport. Twenty-seven pairs of ileal tissues were obtained from the proximal and distal side, respectively, of loop ileostomy after total proctocolectomy. Mucosae were mounted in an Ussing chamber to evaluate glucose-coupled sodium transport. Levels of SGLT-1 mRNA in proximal and distal mucosae were compared by Northern blotting. Villous height and crypt depth were measured to test for correlations between mucosal structure and SGLT-1-mediated sodium transport or mRNA expression levels. Both glucose-coupled sodium transport and expression of SGLT-1 mRNA were significantly lower in distal mucosae relative to proximal mucosae. In distal mucosae, villous height, but not crypt depth, was significantly lower than in proximal mucosae, demonstrating a positive correlation between villous height and SGLT-1 function and expression. Comparative studies of proximal and distal mucosae demonstrated that in addition to hormonal changes, fecal stream is required for full induction of the sodium transport system (which includes SGLT-1-mediated transport) in the remnant ileum following total proctocolectomy.

This study investigated intestinal physiology of piglets at weaning. Piglets (n = 60) weaned at 21 d were food deprived for 2 d and then tube-fed using 2 different diets (a conventional diet vs. a wheat-enriched diet). They were slaughtered at d 0, 2, 5, 8, or 15 postweaning. Jejunum, ileum, and colon were mounted in Ussing chambers. In addition, segments of the proximal jejunum of 4 growing pigs were studied 35 d after weaning. Secretory function was assessed by basal short-circuit current (Isc) and secretagogue-stimulated Isc. Glucose absorption was measured by the increase in Isc after the addition of glucose. Epithelial barrier function was measured by transmucosal resistance (R) and horseradish peroxidase (HRP) fluxes across the epithelium. There were no significant differences between the pigs fed the 2 diets for any of the parameters studied. As already reported, a transient villous atrophy was observed. At the same time, we observed an increased basal Isc in jejunum and colon, increased glucose absorption and a dramatic drop of R in jejunum. These parameters had returned to preweaning values by d 5. Weaning was also followed by long-lasting modifications. In jejunum, responses to the secretagogues and glucose absorption were decreased at wk 2 after weaning and were not different between d 15 and 35. Ileal transmucosal resistance increased on d 5 and was stable thereafter. HRP flux in jejunum declined on d 2 and stayed at this low level throughout the experiment. We conclude that weaning induces transient dramatic changes in intestinal physiology but is also a period of maturation of the intestine.

Dietary supplementations with L-glutamine and/or nucleotides were screened for their effects on intestinal mucosa in 16 female weaning piglets. The animals were transported to the university's facilities 24 hours after weaning. They were grouped four to a pen in controlled environmental conditions and fed one of the following four diets for 28 days: control diet (C); C+0.5% L-glutamine (G); C+0.05% "nucleotides" (N); and C+0.5 % L-glutamine+0.05% "nucleotides" (GN). Individual body weights and feed intake per group were recorded at the beginning and the end of the study as well as weekly during it. There were no significant performance differences among the groups. After 28 days the animals were slaughtered and the distal ileum and liver were examined histologically. Anti-proliferating cell nuclear antigen (PCNA) as well as anti-human macrophage immunostaining, and a modified TdT-mediated dUTP nick-end labeling technique (TUNEL) were performed, and intraepithelial lymphocyte percentage was evaluated to assess morpho-functional aspects of the ileum. Histometry was performed by assessing cell indices and counts of immuno-reactive structures. Feeding G and/or N resulted in an increase in villi (V) height, crypt (C) depth, and a decrease in V:C ratio (P<0.01). In addition, feeding G and/or N resulted in an increase in mitotic mucosal cells (M), and a decrease in apoptotic mucosal cells (A), thus decreasing the A:M index (P<0.01). The percentages of mucosal macrophages were greater in G and/or N groups (P<0.001) than in control piglets, and similarly among the groups the percentages of intraepithelial lymphocytes varied (P<0.01). Our data showed that the diet supplementation with G and/or N had positive effects on some morpho-functional characteristics of piglet ileal mucosa. These ameliorative effects may potentially be linked to a good responsiveness of piglets to a stressful period, like a precocious weaning is in this species.

Both neonatal and C57BL/6 gamma interferon (IFN-gamma) knockout (C57BL/6-GKO) mice are susceptible to Cryptosporidium parvum, but the course of infection is different. Neonatal mice are able to clear the parasite within 3 weeks, whereas C57BL/6-GKO mice, depending on age, die rapidly or remain chronically infected. The mechanism by which IFN-gamma leads to a protective immunity is yet poorly understood. In order to investigate the effect of IFN-gamma on other cytokines expressed in the intestinal mucosa during C. parvum infection, we studied cytokine mRNA expression in the neonates and GKO (neonatal and adult) mice by quantitative reverse transcription-PCR (RT-PCR) at 4 and 9 days after infection. IFN-gamma mRNA levels were quickly and strongly up-regulated in the mucosa of neonatal mice. In GKO mice, the Th1-type response was dramatically altered during the infection, whereas the mRNA expression levels of the Th2-type cytokines interleukin 4 (IL-4) and IL-10 were increased in both mouse models. In the absence of IFN-gamma, the adult knockout mice up-regulated the mRNA levels of inflammatory cytokines, such as IL-1beta, IL-6, and granulocyte-macrophage colony-stimulating factor, in the mucosa, but not tumor necrosis factor alpha (TNF-alpha), whereas all these cytokines were up-regulated in the infected neonatal mice. Further experiments indicated that injections of TNF-alpha into GKO adult mice significantly reduced oocyst shedding. The results of the present study indicate that the resolution of infection is dependent on the expression of Th1-type cytokines in the mucosa of C57BL/6 mice and that TNF-alpha may participate in the control of parasite development.

Background: Little is known about the small intestinal mucosal pattern of Myanmar children., Methods: Duodenal, jejunal and ileal mucosal specimens obtained from children within 6 h of death were examined under a dissecting microscope with the objective of determining villus pattern in relation to site within the small intestine and then correlated with age., Results: Abnormalities in the small intestinal mucosa were detected at a very young age. In children under 1 year of age, the changes are more marked proximally and become less marked distally, perhaps reflecting exposure to the causative agent(s) in early life. Presumably these agents are ingested orally and inactivated progressively. The pattern in older children reflects more severe changes in the ileum., Conclusions: It is postulated that frequent intestinal infections or small bowel bacterial contamination could lead to damage of the intestinal mucosa.

Glucocorticoid exposure accelerates the maturation of small bowel mucosa. We hypothesized that IGF-I, a mitogen and differentiating peptide expressed in small bowel, mediates steroid-induced change within the developing ileum. To investigate this possibility, we intraperitoneally administered 1 microg/gm/d of dexamethasone (DEX) or equal volumes of saline to litter-mate newborn mice. The animals were killed on d 1-3 of life and their ilea were harvested and prepared for microscopy. Tissue sections of ileum were examined for morphologic analyses, mucin staining, immunolocalization of IGF-I and -II, proliferating cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and in situ hybridization for IGF-I transcripts. Morphologic comparisons showed increases in goblet cell number, total cell number, and TUNEL-positive cells within the mucosa of DEX-treated animals. In contrast, the number of smooth muscle nuclei per cross-section was unchanged with DEX treatment despite a reduction in the number of PCNA-positive nuclei and an increased bowel circumference. These findings suggest the muscularis stretches to accommodate increasing bowel diameter. IGF-I peptide was localized to the mesenchyme of all control animals. After 48 h of DEX treatment, IGF-I was detected in the epithelia whereas mesenchymal IGF-I localization appeared diminished. In situ hybridization analyses for IGF-I transcripts showed no differences in localization between the groups. We conclude that DEX administration differentially affects adjacent tissues in the newborn ileum and that the associated changes in IGF-I localization are consistent with its participation in this process.

The organization of the lymphatic system in the rat ileum was investigated by the three-dimensional reconstruction using serial sections after dilatation of lymphatics. This method has an advantage to exclude possible artifacts in the conventional corrosion cast method. The villus possessed several lacteals and connected to each other by sinus. Two or three perpendicularly oriented lymphatics descended and led into the submucosal lymphatic network. In mucosa and submucosa, no valvular structure was detected. This study confirmed the voluminous lacteals and fine network structure of lymphatics in submucosa without valves, suggesting great potential to keep lymph and to drain soluble factors and cellular components.

A mathematical model is presented which examines the extent to which the intestinal epithelium is accessed by drug molecules. Morphological information from the literature for the jejunum, ileum, and colon of the rat and for human jejunum was incorporated. Perturbation theory was used to derive the limiting cases for total access to the entire epithelial surface, for transport by diffusion and by diffusion with convection, respectively. A parameter gamma = square root of (Ph2)/(Db) was identified to provide a measure of the ability of drug molecules to access the entire epithelial surface down to the crypt wells, where P is the cell permeability, D the aqueous diffusion coefficient, h the channel depth between the villi, and b is half the width of the idealized intervillous channel. When gamma << 1, diffusion is not a limitation and the entire surface is fully utilized for absorption of drug. This condition arises with drugs of low permeability and is more likely to be met with colonic than small intestinal epithelium. When gamma >/= 1, diffusion becomes a limitation and then not all of the epithelial surface is functionally accessible to drug molecules, a condition most likely to prevail with drugs of high permeability traversing the jejunum. Furthermore, water flux per se is predicted to have relatively little influence on enhancing surface accessibility. This simple, but quantitative approach showed that the ranking order of permeability jejunum >ileum> colon for low permeable drugs can at least in part be explained by the differences in surface amplification between these different epithelial regions. The analysis also indicates that for highly permeable drugs extreme caution should be exercised in extrapolating permeability measurements in vitro across various preparations and to events in vivo.

With ageing the membrane/soluble form ratio of membrane-boundenzymes increases especially in the ileum and that of peptidases changes rather insignificantly in both portions of the rat small intestine. The soluble forms are supposed to take part in assimilation of food substrates penetrating enterocytes in an unsplit form due to an enhanced permeability of the membranes, particularly those of the ileum.

The morphology of the terminal ileum was studied in 33 male adult pigs of unknown breed. The ileum ended in the cecocolic junction at an acute angle to the cecum. The terminal ileum displayed a cylindrical form (63.6% +/- 8.4 of the cases) more frequently than an ampullary (21.2% +/- 7.1) and/or an infundibular form (15.2% +/- 6.2). The ampullary form is not related to the quadrupedal position of the animal, but is related to the functional phase of the intestine at the time of death. In the mucous tunica of the terminal ileum, longitudinal folds and aggregated lymphoid nodules appeared concentrated along the antimesenteric border.

Purpose: To investigate the effect of microparticle size on gastrointestinal tissue uptake., Methods: Biodegradable microparticles of various sizes using polylactic polyglycolic acid (50:50) co-polymer (100 nm, 500 nm, 1 micron, and 10 microns) and bovine serum albumin as a model protein were formulated by water-in-oil-in-water emulsion solvent evaporation technique. The uptake of microparticles was studied in rat in situ intestinal loop model and quantitatively analyzed for efficiency of uptake., Results: In general, the efficiency of uptake of 100 nm size particles by the intestinal tissue was 15-250 fold higher compared to larger size microparticles. The efficiency of uptake was dependent on the type of tissue, such as Peyer's patch and non patch as well as on the location of the tissue collected i.e. duodenum or ileum. Depending on the size of microparticles, the Peyer's patch tissue had 2-200 fold higher uptake of particles than the non-patch tissue collected from the same region of the intestine. Histological evaluation of the tissue sections demonstrated that 100 nm particles were diffused throughout the submucosal layers while the larger size nano/microparticles were predominantly localized in the epithelial lining of the tissue., Conclusions: There is a microparticle size dependent exclusion phenomena in the gastrointestinal mucosal tissue with 100 nm size particles showing significantly greater tissue uptake. This has important implications in designing of nanoparticle-based oral drug delivery systems, such as an oral vaccine system.

The distribution of fluorescein isothiocyanate dextran 70,000 (FITC-dextran) and mucous gel across the lumen of small intestine was observed as an investigation into the role of mucous gel on permeability in total parenteral nutrition (TPN). Thirty-two rats were randomly divided into two groups fed with either TPN or oral rat food. On day 4 or 7, FITC-dextran (750 mg/kg body weight) was given through the gastroduodenal tube. After 1 hour, blood samples were taken by aortic puncture to analyze plasma FITC-dextran by fluorescence spectrometry. Samples of small intestine with luminal contents were frozen and sectioned in a cryostat for fluorescence microscopy; the same sections were placed in a 0.2% celloidin solution for 3 minutes to preserve mucous gel and stained by periodic acid-Schiff reaction for light microscopy. The plasma level of FITC-dextran after 1 hour of this marker injection showed a significant increase (p < .01) in the TPN group compared with the rat food group on days 4 and 7. Morphologic findings on days 4 and 7 were similar in both the jejunum and ileum: The mucous gel filled the spaces between villi and FITC-dextran centered in the lumen in the rat food group, whereas the mucous gel decreased and FITC-dextran filled the spaces between villi in the TPN group. FITC-dextran and mucous gel showed complementary distributions in both groups. These data suggest that TPN decreases luminal mucous gel and increases permeability of small intestine in rats.

In the rat, a large number of in vitro studies on intestinal fatty acid uptake have been carried out. However, the results obtained under different experimental conditions are often contradictory. The present work is a critical approach to the experimental aspects which may modify in vitro intestinal uptake of fatty acids. Different kinds of intestinal tissue samples (intact, everted or opened rings) were used. The histological changes and the uptake of palmitic acid were measured for each type of sample under different stirring rates, at different incubation times and with micellar solutions of varying composition. It is concluded that 1) opened rings have the highest absorptive capacity with the lowest dispersion; 2) incubation periods longer than 30 minutes do not result in additional palmitic acid uptake and may lead to severe tissue hypoxia as indicated by extensive vacuolization; 3) stirring rates over 1 cycle/sec do not result in increased PA uptake and cause extensive mucosal disruption, particularly in jejunal samples.

Intestinal mucosa of rats was prepared by squeezing the frozen and thawed intestine. The method was much easier compared to the conventional method in which intestine was cut longitudinally or everted and mucosa was scraped. Jejunal mucosal weight prepared by the two methods was not different, but ileal mucosal weight prepared by squeezing was significantly heavier than that by scraped. No significant difference was observed between activity of some brush border enzymes (arylamidase, aminopeptidase, alkaline phosphatase, and sucrase) in mucosa prepared by squeezing and that by conventional scraping method in jejunum. Activity of brush border aminopeptidase and sucrase in ileal mucosa prepared by squeezing was significantly higher than that prepared by scraping.

Location of stretch receptors triggering the peristalsis was investigated in the isolated guinea pig ileum. Peristalsis was cyclically induced by perfusing the lumen with Krebs solution flowing at a constant rate. Peristalsis was promptly abolished by serosally applied 3 x 10(-7) M tetrodotoxin, 10(-4) M lidocaine, 10(-6) M morphine or 10(-5) M nicotine, confirming the claim that peristalsis was neurally regulated by the myenteric plexus. Intraluminal application of 3 x 10(-7) M tetrodotoxin not only blocked the peristalsis, but also inhibited the contractions of the longitudinal muscle elicited by transmural stimulation or 10(-4) M nicotine by the same extent as those by serosal tetrodotoxin, suggesting that the blockade of peristalsis was due to the tetrodotoxin infiltrating into the muscle layer. In contrast, intraluminal application of 0.1% glutaraldehyde or perfusing the lumen with the low NaCl (20 mM)-containing Krebs solution abolished the peristalsis without critically inhibiting the neurogenic contractions of the longitudinal muscle, indicating that the blockade of peristalsis by these intraluminal treatments was ascribed to the actions on the mucosal layer. These results may imply that stretch receptors are located in the mucosal layer of the guinea pig ileum, and the impairment of the functions of these receptors by the intraluminal treatments leads to the blockade of the peristalsis.

Intestinal mucosal morphometry and ileal epithelial renewal were studied in conventional (CV) and germ-free (GF) rats fed either poorly digestible amylomaize or normal maize starch diets. Intestinal morphometry and position of labelled enterocytes were studied at various times after tritiated thymidine injection. With amylomaize starch diet, no difference was observed in the size of crypts (C), villi (V) and C + V between duodenum and jejunum both in CV and GF rats. In the ileum, however, values were significantly lower than those in the duodenum and jejunum. Furthermore, the presence of the microbial flora led to higher values when compared with GF values. Despite the morphological modifications in the ileum, no significant difference was detected in the labelled cell positions and epithelial renewal time between CV and GF values. This suggests that the resistant part of amylomaize starch was responsible for the modification in mucosal morphometry and the longer ileal epithelium renewal time in CV rats which then becomes similar to that in GF rats.

It has been hypothesized that, following colectomy and endorectal ileal pullthrough with ileal reservoir (PTR), reservoir tissue might lose some of its normal nutrient transport capacity and assume properties of the colon. Whether reservoir size influences the expected alterations in normal mucosal absorption and thus contributes to changes in intraluminal ecology has not previously been investigated. To study this, the everted intestinal sleeve technique was used to measure uptake of four nutrients in two groups of dogs who underwent PTR: five with a small (5 cm) lateral reservoir and five with a large (18 cm) reservoir. Mucosal samples were taken from normal ileum and colon and from reservoirs 3 months postoperation. Active uptake of carbohydrates (glucose), amino acids (proline), and bile acids (taurocholate) and passive uptake of short chain fatty acids (propionate) were markedly decreased in mucosa of both reservoir sizes compared to normal ileum (P less than 0.05, t test) and more closely approximated that of normal colon. Uptake of glucose, proline, and taurocholate in large reservoirs was significantly less than that in small reservoirs (P less than 0.05). We conclude that (1) ileal reservoir mucosa has a significantly reduced capacity for nutrient uptake, (2) ileal mucosa in small reservoirs shows higher nutrient uptake rates than mucosa in large reservoirs, and (3) short, well-emptying reservoirs appear best suited to optimizing the intraluminal environment and thus enhance reservoir function when performing PTR.

Scanning electron micrographs are presented of the ileal epithelium of mice aged 5, 15, 20 and 25 days. During this period the villous pattern develops to full maturity. By the twentieth day of life a segmented filamentous micro-organism colonizes the ileal epithelium and is firmly attached via a small segment. During the first days of colonization the segmented filamentous micro-organisms themselves are subcolonized by small rod-shaped bacteria, presumably lactobacilli. At the age of 25 days this subcolonization was no longer observed.

Normal histology, glycogen and alkaline phosphatase have been studied in the mucosa of human fetal ileum between 28 and 140 days of gestation. From 112 days onwards, the perinuclear, supranuclear and infranuclear vacuolation, striate border, and basement membrane of the columnar epithelial cells of the villi, and the very close proximity of the latter to blood vessels, all support the idea that the cells are actively engaged in transport of materials. Alkaline phosphatase and glycogen become conspicuous in the cells at this stage. It is argued that by 112 days the epithelial cells of the ileum are absorbing glucose amniotic fluid as well as secreting mucus.

The dog jejunum is a much denser tissue than the ileum, with a greater weight per unit length and higher proportion of mucosal tissue. Morphometric analysis reveals longer and wider villi, deeper crypts and larger enterocytes in the jejunal mucosa. Uptake of phenylalanine or beta-methyl-glucoside by tissue slices in vitro is slightly greater in jejunal than in ileal tissue. The levels of acid phosphatase and alkaline phosphatase in the individual enterocytes are significantly greater in the jejunum, according to quantitative histochemical analysis. The absorption of water, sodium, potassium, chloride and glucose in vivo is significantly smaller in the jejunal than in ileal loops, particularly when expressed in terms of unit mucosal weight. Sodium and water absorptions are stimulated by glucose at both sites, but the stimulation is significantly greater in the ileum. Opposite results have been obtained in rats where the transport of phenylalannie in vitro is greater in the ileum, but water, electrolyte and glucose absorption in vivo is greater in the jejunum.

In this study the early phase of the morphological adaptation of rat ileum after a proximal resection of 60% has been studied using microdissection and cell labelling techniques. Resected rats and sham-operated controls were killed 2, 4, 6, 10 and 12 days after surgery. Intraperitoneal injections of 3H-thymidine were carried out 24 or 12 h prior to sacrifice. In the latter groups mitotic arrest was achieved by vincristine. A stereo-microscope was used to measure and calculate the following parameters: intestinal diameter; villus: height, width, breadth at base and apex, surface, enterocytes per 100 micrometers length, cell pool, number of villi and absorptive surface per mm2 serosal area; crypt: length, enteroblasts per 100 micrometers length and per column, cell columns and mitoses per crypt, cell pool, crypts, and mitoses per unit serosal area; cell kinetics: migration rate, villus transit time. To test the influence of treatments, postoperative time course and the location of the intestinal segment and their possible interactions, factorial analyses of variance were carried out on the parameters investigated. The main findings, demonstrated for the first time, were: 1. An increase in the villus surface which was achieved by proportional enlargement of villus geometry; 2. This increase in the villus surface led to an enlarged absorptive surface per unit serosal area; 3. A reduction of villus transit time of the individual enterocyte; 4. A most pronounced magnitude of adaptative response in the proximal remnants which was gradually diminished in aboral direction, and 5. A sequential course of adaptative response of the various crypt parameters investigated.

Mice were injected three times a day for 12 days with 300 micrograms/kg body weight of gastrin G17 or 37.5 Ivy dog U/kg body weight of CCK or saline. Other mice were also injected four times an hr for 1 hr with 7.5 micrograms/kg of gastrin, nine Ivy dog U/kg of CCK or saline; 1 hr before killing, they were injected with tritiated thymidine to evaluate the labelling indices in peptic, antral, duodenal, jejunal, and ileal mucosae. Four hours after the first injection of the two peptides, the peptic labelling indices increased while those of intestinal mucosa increased 8 hr after these injections. Long-term injections of CCK had a trophic effect on secretory cells of the digestive tract: the number of gastric zymogenic cells, Paneth cells, and the mucous cells of Brünner glands were hypertrophied. The pepsin, amylase, chymotrypsin, and lysozyme activities increased in stomach, exocrine pancreas, and intestine, respectively. Neither parietal cells nor intestinal enterocytes and hydrolase activities were affected. The trophic effect of long-term injections of gastrin is confirmed on parietal cells and exocrine pancreatic parenchyma and is demonstrated in Paneth cells. Confirming cytological results, pancreatic lipase and amylase activities and intestinal lysozyme activity were increased after gastrin. Although CCK and gastrin have a structural analogy, these two peptides did not affect the same cellular types. A specific action of CCK on the main secretory cells of the digestive mucosa is demonstrated.

This study was undertaken to examine the effect of feeding 2 defined-formula diets, Isocal and Portagen, on intestinal morphology and transport function in rabbits subjected to an ileal resection, and in control animals with an intact intestinal tract. Neither ileal resection nor feeding Isocal or Portagen significantly altered jejunal mucosal surface area. In animals with an intact intestinal tract, feeding Isocal was associated with decreased jejunal uptake of 2 mM glucose, whereas both Isocal and Portagen were associated with increased jejunal uptake of 40 mM glucose, and increased ileal uptake of 2 mM glucose, as compared with rabbits fed chow. In animals with an ileal resection, feeding Isocal was associated with increased jejunal and colonic uptake of galactose, whereas jejunal uptake of glucose was unaffected. Thus, (1) feeding defined-formula diets alters the intestinal active uptake of sugars without altering intestinal mucosal surface area; (2) sugar uptake rates were generally higher in animals fed Isocal than in those fed Portagen; (3) ileal resection obscured the differences in the jejunal uptake of higher concentrations of glucose observed in control rabbits (with an intact intestinal tract) fed these defined-formula diets; and (4) the differences in the effects of defined-formula diets on sugar uptake in control and resected animals was likely due to a direct effect on the glucose and galactose carrier(s), rather than to an indirect effect on food consumption, body weight gain, intestinal morphology, or the effective resistance of the intestinal unstirred water layer. It is suggested that the functional differences observed between animals fed Isocal versus Portagen may be due to the varying source of lipids and proteins in these diets, their different ratios of saturated-to-polyunsaturated fatty acids, and their different percent content of carbohydrate.

Intestinal absorption and intraluminal pressures were measured at perfusion rates between 0.3 and 200 ml per min in the rat ileum in vivo. Glucose absorption from a 72 mM glucose solution and tritiated water ([3-H]water) diffusion rate were used to reflect changes in mucosal surface area. Glucose absorption from a 4 mM solution was used to indicate changes in unstirred water layer thickness, and mannitol and urea absorption were used as markers of passive mucosal permeability. In a partially obstructed intestinal segment, designed to keep the gut partially filled even at low perfusion rates and to minimize surface area change as perfusion rate was increased, glucose absorption from a 4 mM solution increased by 150% as perfusion rate was increased from 1 to 100 ml per min. Forty per cent of this increase was due to increased surface area (estimated from the change in [3-H]water absorption), and 110% of the increase is attributed to thinning of the unstirred water layer. Because mannitol absorption was zero at all perfusion rates, none of the enhanced glucose absorption rate need be attributed to enhanced mucosal permeability, even though intraluminal pressure was increased at higher perfusion rates. Urea absorption was apparently influenced by surface area and by permeability changes, but not by the thickness of the unstirred water layer. This model was also used to explore the effect of unstirred water layer thickness on the inhibitory effect of sodium replacement by magnesium on glucose absorption from a 4 mM glucose solution. Inhibition by sodium removal was equal at 1, 10, 100, and 200 ml per min perfusion rates, suggesting that unstirred water layer thickness does not play an important role in the interaction of glucose and sodium absorption when intraluminal sodium concentration is reduced. Additional experiments in an unobstructed ileal segment revealed that the major effect of enhanced perfusion rate is to increase mucosal surface area; relatively high rates of perfusion were required to thin significantly the unstirred water layer when intestinal outflow was not partially obstructed.

The present EM morphometric analysis is a continuation of a series of studies in which the changes of the microvillous surface area of the small intestine was investigated in the course of the entire life span of the female rat. It was concluded from the present data that the alterations of the ileal microvillous surface area are more balanced in the young, pregnant, lactating, adult, old and senile animals than that was observed in the case of the duodenum and jejunum. Positive correlations were found between the parameters height and surface area and, density and surface area measures of the microvilli. Microvillous width and density revealed an inverse relationship mainly in the case of the young and adult animals.

1. The function and structure of dog ileal mucosa was examined immediately after arterial ischaemia for 1 h and 1, 3 or 7 days after the trauma. 2. Immediately after the ischaemia, there was a net movement of water and ions into a luminal perfusate in vivo. One day later, there was no net movement of water and electrolytes but net absorption returned on the third day. 3. Active transport of phenylalanine or beta-methylglucoside by mucosal strips in vitro was abolished immediately after the trauma but was largely restored 1 day later. There was a close correlation between glucose absorption in vivo and beta-methylglucoside uptake in vitro. 4. Morphological study revealed pronounced desquamation of enterocytes immediately after the trauma. The regenerating mucosa had shorter villi and crypts, and lower enzyme activities assessed histochemically 1 day later. Most parameters had returned to normal by the third post-operative day.

The development of the intra-intestinal artery in the Australian lungfish, Neoceratodus forsteri was studied by dye injection. The right arterior wall of the midgut changes to become the valvular wall of the original part of the spiral valve owing to the shift of the foregut towards the posterior and the left ventral to the midgut. The anlage of the intra-intestinal artery appears in the blood vascular network on the valvular wall of the original part of the spiral valve; this network receives arterial blood from the primitive coeliacomesenteric artery. The intra-intestinal artery is formed in such a manner that this anlage extends posteriorly in the blood vascular networks in the successive spiral valves.

Previous studies of dietary protein intake and calcium balance demonstrate decreased fecal calcium excretion with high-protein diets. To determine whether a duodenal or ileal calcium transport response could account for these findings, we examined calcium transport by these two segments directly by in situ perfusion. Weight-matched growing rats were pair-fed isocaloric diets for 6-8 days containing 89% protein (casein), 39% and 0% protein. Sucrose was substituted for the decreased casein in the 39% and 0% protein diets. Each diet also contained 5% fat, a mineral mix, and vitamins. Calcium content of all diets was 0.5%. Body weight was maintained by the 39% protein group; weight loss was 5% for the 89% protein group and 18% for the 0% protein group. Small-intestinal weight as a percentage of body weight was the same for the three groups. For both the duodenum and the ileum, mucosal dry weight per centimeter was greater in the 39% protein group than either the 89% protein or 0% protein group. Calcium absorption per gram dry weight of mucosa (absorptive specific activity) was the same for all diet groups, but because of the greater mucosal weight per unit length in the 39% protein group, absorption per centimeter was increased in this group. In conclusion, although we found no direct relation between dietary protein and mucosal absorptive specific activity for calcium, calcium absorption was determined by the amount of mucosa which was dependent on protein intake and reflected the nutritional status of the body.

The quantitative significance of intraluminal peptide hydrolases in the terminal stages of peptide digestion has been investigated, and the precise origins of these enzymes have been determined. Intestinal contents and mucosae were obtained from rats anethetized with ether. Experiments carried out on pancreaticobiliary secretions and germfree rats show that pancreatic and bacterial enzymes do not contribute significantly toward the luminal digestion of dipeptides. Chemical assay data, thermostability studies, and examination of electrophoretic mobilities of luminal peptide hydrolases indicate that jejunal enzymes originate predominantly from the cytoplasm of intestinal mucosal cells, whereas the brush border of muosal cells is a major source of the enzymes in the ileum. With glycl-L-phenylalanine and L-phenylalanyl-glycine as substrates, jejunal luminal activity was less than 2.6% of mucosal activity. Brush-border peptide hydrolase activity in ileal contents, however, was 11.9% and 40.7% of mucosal brush-border activity for the two substrates. Luminal enzymes thus play an insignifcant role in the terminal digestion of peptides in the jejunum, but have a much more important role in the ileal digestion of peptides.

Oral intake of an elemental diet maintains small intestinal mucosal mass compared to the atrophy seen after intravenous infusion of the same diet. The greatest difference in intestinal mass occurs in the proximal bowel and is thought to occur because of rapid absorption in the proximal small bowel. This study was designed to determine the effects of the individual components of the elemental diet and their site of administration within the small bowel on small intestinal mass. Rats were maintained on intravenous alimentation and the proximal gut (by intragastric infusion) or the ileum was continuously infused with equal volumes of 30% dextrose, 5% dextrose, 5% amino acids, saline, or 30% mannitol. After 1 week of combined intravenous alimentation and gut infusion, the rats were killed and parameters of small intestinal epithelial mass were determined sequentially for the entire bowel. Although saline- and mannitol-infused controls did not differ from uninfused intravenously fed rats, proximal infusion of 30% dextrose reproduced the effects of a complete elemental diet. Proximal infusion of amino acids but not 5% dextrose had a limited effect on the duodenum and jejunum. Ileal infusion of 30% dextrose led to local hyperplasia of the site of infusion and in addition produced hyperplasia of the proximal gut. Ileal amino acid infusion, but not 5% dextrose infusion, led to local ileal hyperplasia. We conclude that: (1) intraluminal dextrose and amino acids have direct effects in maintaining gut mass (2) the gut is more responsive to amino acids compared to 5% dextrose, and (3) ileal 30% dextrose infusion leads to remote effects in the proximal gut, perhaps mediated by hormonal or neurovascular factors.

The small intestinal mucosa of rats (male, aged 8 weeks) was isolated by the Bjerknes and Cheng's method (1981): the anesthetized rats were perfused through the left ventricle with a solution of ethylenediaminetetraacetic acid (30 mmol/l) in calcium-magnesium-free Hanks' solution, and then the mucous epithelium was removed from a segment of the duodenum, jejunum and ileum by means of vibration. Three-dimensional images of crypts on the isolated mucosa were obtained by scanning electron microscopy. The length and number of the crypts between the villi were observed to decrease along the intestine from the duodenum to the ileum. The majority of intestinal crypts were simple non-branched tubular glands, however, budding and bifurcation of the crypt ends were often observed. It was relatively rare to find longitudinally split crypts. The shapes of the crypts seems to denote various stages of the proliferation of crypts.

Several factors might affect the growth of neomucosa after serosal patching of small intestinal defects. Often only short segments of small intestine can be patched because of limited serosal surface and anatomic factors. The purpose of this study was to determine the influence of patch size on neomucosal growth. Twenty male New Zealand white rabbits underwent patching with colon serosa of either a 2 X 15-cm distal ileal defect (n = 10) or three 2 X 5-cm ileal defects (n = 10). There was significantly greater coverage of the patched defect by neomucosa in the triple patch group (99.4% vs 93.1% P less than 0.005) and significantly more of the smaller defects were completely covered by neomucosa than the larger defects (12 of 15 vs 0 of 5, P less than 0.05) at 8 weeks. The final area of the defect was 27.5 and 32.8% of the initial patched area respectively for the single and triple patches. Microscopically there was no difference in villous height or crypt depth, but crypt density was significantly greater in the triple group (207 +/- 11 vs 186 +/- 17 crypts/mm, P less than 0.05). In vitro glucose uptake and disaccharidase activity were similar in both groups. Patching multiple small intestinal defects results in more rapid neomucosal growth than a single large defect of the same surface area. This might be due to a greater circumference exposed to surrounding normal mucosa with a resultant increase in crypt density. Since function and villous development of the neomucosa are similar, multiple patches should result in a greater increase in absorptive capacity.

Many water-soluble compounds have been shown to pass from the small intestinal mucosa into the lumen. In this work, the loss of lipids from the mucosa was investigated by perfusion experiments in rats, using 0-15M NaCl or buffer solutions over range of pH, with or without the addition of 5-7 or 11-4mM taurocholic acid. Perfusates were extracted for the estimation of individual lipids and for DNA, which is a measure of cell loss. The results suggest that free fatty acids reach the lumen by diffusion and that their solubility in the luminal fluid is a factor determining their rate of loss. Triglycerides, cholesterol, phosphatidyl ethanolamine, and phosphatidly choline are present onlyas the result of desquamation of mucosal cells.

Continent ileostomy reservoirs were constructed in dogs. Nine to 29 days after formation of the pouches, they were excised together with a loop of adjacent ileum for biochemical and morphological assessment. The villous and epithelial cell heights were reduced, whereas villous width and mitotic index were increased. The mucosa of the pouch was able to absorb phenylalanine and Beta-methyl-glucoside against a concentration gradient, although this absorptive capaciti was lower than that of normal ileum. Similar considerations applied to oxygen consumption. The results indicate that the mucosa of the pouch undergoes transformation, but the intergrity of the epithelial layer is maintained.

The secretory responses to cholera enterotoxin and prostaglandin E1 (PGE1) are dependent upon elevation of the intracellular levels of cyclic AMP. Although several previous reports have suggested that intestinal secretion due to cholera enterotoxin and PGE1 may be confined to the crypt cells, this matter has been incompletely resolved. These studies were undertaken to define the activity of adenylate cyclase in villus and crypt cells from rabbit and rat intestine, and to determine the influence of enterotoxin and PGE1 on this activity, Mucosal fractions were prepared from rabbit ileum with a planing device, and from rat distal small intestine by a vibration technique. In both species base line adenylate cyclase activity was greater in crypt than in villus cells. After exposure to cholera enterotoxin in vivo, adenylate cyclase activity was enhanced in all fractions prepared from rabbit ileum, and the response was most marked in villus cells. Furthermore, adenylate cyclase in membranes prepared from both rat villus and crypt intestinal cells was responsive to the in vitro addition of PGE1. The results of these studies indicate that both villus and crypt cells contain one of the important components required for the cyclic AMP-mediated secretory response, namely, a cholera enterotoxin and PGE1-sensitive adenylate cyclase activity. Since an increased level of cyclic AMP alone may not be sufficient to evoke a secretory response, these studies do not clarify the extent to which each of these major cell types may participate in cyclic AMP-mediated secretion.

Germ-free rats were inoculated with microbial flora from feces of conventionally reared rats and the mucosal structure was quantitatively observed at different time intervals after the inoculation and at different regions of the small intestine. In the ileum, desquamation figures were frequently seen on the villus tip, and several parameters of the mucosal elements, i.e., villus and crypt lengths, mitotic figures, goblet cells and thickness of lamina propria were significantly increased after the inoculation. On the other hand, in the duodenum and jejunum, such parameters except for the lamina propria showed no remarkable change during the course of the experiment, though the villus/crypt ratio increased temporarily at half a day after the inoculation. These regional differences of the mucosal response to the inoculation may be due to the different populations of microbial flora which settled in each region of the small intestine.