Normal Jejunum Research Articles

Regulation of Epithelial Differentiation in Rat Intestine by Intraluminal Delivery of an Adenoviral Vector or Silencing RNA Coding for Schlafen 3

Although we stimulate enterocytic proliferation to ameliorate short gut syndrome or mucosal atrophy, less effort has been directed at enterocytic differentiation. Schlafen 3 (Slfn3) is a poorly understood protein induced during IEC-6 enterocytic differentiation. We hypothesized that exogenous manipulation of Slfn3 would regulate enterocytic differentiation in vivo. Adenoviral vector coding for Slfn3 cDNA (Ad-GFP-Slfn3) or silencing RNA for Slfn3 (siSlfn3) was introduced intraluminally into rat intestine. We assessed Slfn3, villin, sucrase-isomaltase (SI), Dpp4, and Glut2 by qRT-PCR, Western blot, and immunohistochemistry. We also studied Slfn3 and these differentiation markers in atrophic defunctionalized jejunal mucosa and the crypt-villus axis of normal jejunum. Ad-GFP-Slfn3 but not Ad-GFP increased Slfn3, villin and Dpp4 expression in human Caco-2 intestinal epithelial cells. Injecting Ad-GFP-Slfn3 into rat jejunum in vivo increased mucosal Slfn3 mRNA three days later vs. intraluminal Ad-GFP. This Slfn3 overexpression was associated with increases in all four differentiation markers. Injecting siSlfn3 into rat jejunum in vivo substantially reduced Slfn3 and all four intestinal mucosal differentiation markers three days later, as well as Dpp4 specific activity. Endogenous Slfn3 was reduced in atrophic mucosa from a blind-end Roux-en-Y anastomosis in parallel with differentiation marker expression together with AKT and p38 signaling. Slfn3 was more highly expressed in the villi than the crypts, paralleling Glut2, SI and Dpp4. Slfn3 is a key intracellular regulator of rat enterocytic differentiation. Understanding how Slfn3 works may identify targets to promote enterocytic differentiation and maintain mucosal function in vivo, facilitating enteral nutrition and improving survival in patients with mucosal atrophy or short gut syndrome.

Glucose-dependent insulinotropic polypeptide regulates dipeptide absorption in mouse jejunum

Glucose-dependent insulinotropic polypeptide (GIP) secreted from jejunal mucosal K cells augments insulin secretion and plays a critical role in the pathogenesis of obesity and Type 2 diabetes mellitus. In recent studies, we have shown GIP directly activates Na-glucose cotransporter-1 (SGLT1) and enhances glucose absorption in mouse jejunum. It is not known whether GIP would also regulate other intestinal nutrient absorptive processes. The present study investigated the effect of GIP on proton-peptide cotransporter-1 (PepT1) that mediates di- and tripeptide absorption as well as peptidomimetic drugs. Immunohistochemistry studies localized both GIP receptor (GIPR) and PepT1 proteins on the basolateral and apical membranes of normal mouse jejunum, respectively. Anti-GIPR antibody detected 50-, 55-, 65-, and 70-kDa proteins, whereas anti-PepT1 detected a 70-kDa proteins in mucosal homogenates of mouse jejunum. RT-PCR analyses established the expression of GIPR- and PepT1-specific mRNA in mucosal cells of mouse jejunum. Absorption of Gly-Sar (a nondigestible dipeptide) measured under voltage-clamp conditions revealed that the imposed mucosal H(+) gradient-enhanced Gly-Sar absorption as an evidence for the presence of PepT1-mediated H(+):Gly-Sar cotransport on the apical membranes of mouse jejunum. H(+):Gly-Sar absorption was completely inhibited by cephalexin (a competitive inhibitor of PepT1) and was activated by GIP. The GIP-activated Gly-Sar absorption was completely inhibited by RP-cAMP (a cAMP antagonist). In contrast to GIP, the ileal L cell secreting glucagon-like peptide-1 (GLP-1) did not affect the H(+):Gly-Sar absorption in mouse jejunum. We conclude from these observations that GIP, but not GLP-1, directly activates PepT1 activity by a cAMP-dependent signaling pathway in jejunum.

Non coeliac gluten sensitivity.

In the past, the terms gluten sensitivity and coeliac disease have been used synonymously but this is not acceptable since gluten sensitivity can occur in subjects who do not have coeliac disease. The entity of non coeliac gluten intolerance has been regarded as a new diagnosis (1) but it is better to consider it an old diagnosis recently rediscovered and embellished. In the late 1970s brief case reports indicated that that some patients were wheat sensitive but did not have coeliac disease (2-4). During this time 17 patients with chronic diarrhoea who had received no definitive diagnosis or effective treatment were investigated at the Birmingham General Hospital, UK (5). Of these, nine, all women, had suffered persistent diarrhoea for up to 20 years, averaging five years, which was often socially incapacitating and nocturnal and which responded to a gluten free diet. The eight remaining patients showed no such sustained benefit. Among the responders, abdominal pain, abdominal distension, malaise and lassitude were also common symptoms. Routine blood tests were normal and of six tested, none had steatorrhoea. Only three carried the HLA-B8 phenotype. Multiple jejunal biopsies taken from these nine patients generated 54 pieces of macroscopically normal jejunum although with a slight increase in cellularity. Plasma cell counts in the lamina propria and intraepithelial lymphocytes were significantly increased compared with 17 normal controls and the eight non-responders. The cell counts however, were much lower than in untreated coeliac disease (6). The response of these nine patients to a gluten free diet was dramatic. Within two weeks each noted a marked improvement in their symptoms. All of the patients elected to remain on the gluten free diet and at the time of the report had taken it for 4-6 years. Repeat jejunal biopsies revealed a return to normal of the cellular infiltrate. Gluten challenge resulted in a recurrence of symptoms within 8-12 hours and which could last as long as a week. The mucosal plasma cell numbers increased slightly (mean rise of 297 cells/mm2) 24 hours after challenge but there were no changes in eosinophil or intraepithelial lymphocyte counts. Apart from these changes in plasma cell numbers no other immunological abnormalities were detected after gluten challenge. Of interest, in the eight patients who did not respond to the gluten free diet, the cell counts were within normal limits even after gluten challenge. It was concluded from this study that non coeliac gluten intolerance affected some patients and could be successfully treated by diet but the mechanisms responsible for producing ill-health were unknown.

Regeneration of enteric ganglia in mechanically lengthened jejunum after restoration into intestinal continuity

PurposeWe previously demonstrated that it is feasible to lengthen intestinal segments with mechanical force and to restore them back into intestinal continuity. The changes in the enteric ganglia in the lengthened intestinal segments have not been described. MethodsA 1-cm segment of rodent jejunum was isolated from intestinal continuity and was lengthened using a spring. After lengthening, jejunal segments were either retrieved (n=4) or restored into intestinal continuity (n=4). Rats with restored segments were euthanized 2 to 3 weeks later. Ganglia were identified and quantified by immunostaining of histological sections. ResultsThe normal jejunum had 51±5 myenteric and 31±2 submucosal ganglia per circumferential tissue section. Lengthened segments had 21±7 myenteric and 2±2 submucosal ganglia. Restored segments had 46±14 myenteric and 10±10 submucosal ganglia. Circumferential density of ganglia followed a similar pattern. ConclusionMechanical lengthening led to a paucity of submucosal and myenteric ganglia. After restoration into continuity, the number increased toward normal, indicating regeneration of the enteric ganglia. The function of regenerated ganglia needs to be assessed in the future.

Distraction-Induced Intestinal Enterogenesis

Significant bowel lengthening can occur in an isolated intestinal segment with the use of linearly directed distractive forces, resulting in increased surface area and epithelial cell proliferation. We hypothesized that reimplantation of this lengthened intestine into normal jejunum would preserve this gain in intestinal length and function similar to normal jejunum. An intestinal lengthening device was inserted into isolated jejunal segments in pigs, and fully expanded over 8 days. Lengthened segments were then reimplanted into normal intestinal continuity. Pigs were studied after another 28 days. Function was assessed by motility, mucosal enzyme activity, barrier function, and intestinal ion transport. Lengthened segments were significantly longer than control segments and had nearly 2-fold greater surface area. Bowel lengthening was maintained 4 weeks after reimplantation. Motility after reimplantation was similar to nonoperated pigs. Barrier function, mucosal disaccharidase levels, and electrophysiologic measures declined immediately after lengthening but returned to nearly normal levels 28 days after reimplantation. Bowel lengthening results in a transient decline in mucosal absorptive function and smooth muscle contractility. However, function approaches that of normal bowel after reimplantation into enteric flow. These data may support the use of this technique as a potential new option for the treatment of patients with short bowel syndrome.

Restoration of mechanically lengthened jejunum into intestinal continuity in rats

Purpose Prior studies demonstrated the feasibility of lengthening intestinal segments with mechanical force, but no previous studies have restored the lengthened segment back into intestinal continuity. Methods A 1-cm segment of isolated rat jejunum was lengthened using a Nitinol spring. After lengthening, this segment was restored into intestinal continuity via a transection of the intact small intestine. Rats were euthanized 2 weeks later to retrieve the restored intestinal segment for histologic and enzymatic analyses. Results The isolated jejunal segments were initially lengthened to 3.3 ± 0.9 cm. After the lengthened segments were restored into intestinal continuity for 2 weeks, the final length of the restored segment was 1.9 ± 0.7 cm. All rats continued to gain weight, and the intestine proximal to the restored jejunal segment remained normal 2 weeks later. The restored jejunal segment had an increase in crypt depth and no difference in villus height compared with normal jejunum. Sucrase activity in the restored segment was not different from that in normal jejunum. Conclusion Mechanically lengthened jejunum can be restored into intestinal continuity and appears to have normal function. This further demonstrates the feasibility of mechanical enterogenesis as a potential therapy for short bowel syndrome.

Significance of decreased apoptosis, role of Bid expression and Bcl-Xl/Bid ratio in human jejunal stromal tumors

Given that the studies on human small intestinal stromal tumors are very limited, our study was designed to determine the significance of apoptosis, the role of some apoptosis-related proteins, including Bax, Bad, Bid, Bcl-2, Bcl-Xl, and Bcl-W, in jejunal stromal tumors (JST). For this purpose, 52 samples were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and immunohistochemistry, including 40 cases from normal jejunum and 12 cases from the JST. The results showed that a significantly decreased apoptosis was observed in JST compared with normal jejunum (median of apoptotic index, 0.13% vs 15.17%, p < 0.001). In univariate analysis, statistically significant differences were shown in percentage of positive-expression of Bid (0.0% vs 77.5%, p < 0.001), Bcl-2 (91.7% vs 42.5%, p = 0.003), and Bcl-Xl (75.0% vs 35.0%, p = 0.014), but not in Bax, Bad, and Bcl-W. Moreover, Bcl-Xl was an independent parameter associated with JST by multivariate Logistic analysis. For the role of ratios of anti-apoptotic proteins to pro-apoptotic proteins, Bcl-Xl/Bid ratio was the most preferable index. In conclusion, decreased apoptosis and expression of Bid, increased level of Bcl-Xl may play some important roles in human JST, and Bcl-Xl/Bid ratio may be as a new potentially associated index, although they should be validated in more studies.

Effects of Salmonella on spatial-temporal processes of jejunal development in chickens

To study effects of Salmonella enteritidis on morphological and functional changes in chicken jejunal development, we analysed gene expression profiles at seven points post-infection in 1–21 day-old broiler chickens. Nine clusters with different gene expression patterns were identified, and the genes in each cluster were further analyzed by a functional annotation clustering method (DAVID). Functional and morphological developmental processes dominated in all the nine clusters. Salmonella infection caused delays in several intestinal-morphological processes, whereas functional metabolic processes occurred in a similar spatial-temporal frame compared to normal jejunum development. A clear difference between normal developing- and Salmonella disturbed jejunum was the higher expression of genes involved in cell turn-over at early stages in the infected jejunum. Surprisingly, we found no clustered immune related processes in the infected birds. To compare the immunological processes between control and Salmonella infected chickens, the gene expression data was superimposed on known immunological KEGG pathways. Furthermore an in-depth analysis on the immune gene level was performed. As expected, we did find immunological processes in the Salmonella infected jejunum. Several of these processes could be verified by immunohistochemistry measurements of different immunological cell types. However, the well-ordered spatial-temporal development of the immune system, as observed in control non-infected animals, was completely abolished in the infected animals. Several immunological processes started much earlier in time, whereas other processes are disorganised. These data indicate that normal morphological and immunological development of jejunum is changed dramatically by a disturbance due to Salmonella infection. Due to the disturbance, the well-organized spatial-temporal development of morphological processes are delayed, those of the immunological development are scattered, whereas metabolic functional processes are almost not affected. This demonstrates the flexibility of developmental processes in the broiler chicken intestine.

Post operative neutrophilic inflammation in equine small intestine after manipulation and ischaemia

Post operative ileus (POI) remains an important cause of post operative morbidity and mortality in the horse. However, clinical progression of naturally occurring cases of POI in both horse and man does not entirely support the 'neurogenic' hypothesis as the sole mechanism of POI; and the hypothesis that inflammation plays a major role at 12-24 h after surgery requires validation. An inflammatory infiltrate in the muscularis externa and myenteric plexus of equine jejunum is present 18 h following a period of ischaemia. Samples of normal jejunum, jejunum from the proximal resection margins of clinical cases and jejunum obtained 18 h after 1 or 2 h ischaemia or manipulation alone were evaluated for neutrophil infiltration. Samples obtained 18 h after surgery were additionally evaluated for leucocyte activation using calprotectin immunohistochemistry. Results were evaluated by ANOVA and P < 0.05 was considered significant. Significant neutrophilic inflammation was identified in the samples from the proximal resection margins of clinical cases compared to uninjured jejunum. In experimental cases, neutrophilic inflammation appeared to be increased further by 18 h and was identified through all intestinal layers, particularly in the serosa, fascial planes around circular and longitudinal muscle fibres, and myenteric plexus. This elevated level of neutrophilic inflammation was mirrored by an increased number of calprotectin-positive cells in these intestinal layers, indicating leucocyte activation. Significant neutrophilic inflammation occurs in equine jejunal myenteric layers 18 h after surgery. This neutrophilic inflammation coincides with the clinical time point at which POI is identified and may indicate that inflammatory pathways, rather than solely neurogenic pathways, are responsible for POI in the horse.

Do radiologists agree on the quality of computed tomography enterography?

This study aimed to assess variation between radiologists evaluating the quality of multi-detector computed tomography enterography. For 40 consecutive examinations, three experienced radiologists independently rated the following quality variables: % length of adequately filled bowel, bowel lumen diameters, bowel wall delineation, superior mesenteric vein, and bowel wall enhancement, artefacts, and total quality. We calculated the mean difference between observers with standard deviation (SD) for continuous variables and % total agreement, exact Fleiss kappa, and P-values (McNemar's test) for categorical variables. Depending on bowel segment (duodenum distal to bulb, jejunum, ileum, terminal ileum), mean difference between observers ranged from two to 33 (SD from 11 to 32) for % length of adequately filled bowel judged subjectively, 0-2 (SD 0-3) mm for smallest bowel lumen diameter and 0-4 (SD 3-7) mm for largest bowel lumen diameter. Agreement on bowel wall delineation was 80%/kappa 0.50 in duodenum, 90%/kappa 0.57 in jejunum, 75%/kappa 0.14 in ileum and 88%/kappa 0.17 in terminal ileum, where ratings differed between observers (P < 0.04). Agreement was 65%/kappa 0.18 for bowel wall enhancement judged subjectively. For contrast enhancement measured in Hounsfield Units, mean difference between observers ranged from two to 11 (SD 12-15) in normal jejunum wall and zero to one (SD 4-5) in the superior mesenteric vein depending on observer pair. Agreement was 78%/kappa 0.12 for image artefacts. Rating of total examination quality (good/optimal versus poor/very poor) differed between observers (P < 0.01); agreement was 60%/kappa 0.41. Many subjective evaluations varied between observers. We believe that measurements of bowel lumen diameters and contrast enhancement may be preferable.

Cyclopentenyl cytosine has biological and anti-tumour activity, but does not enhance the efficacy of gemcitabine and radiation in two animal tumour models

Cyclopentenyl cytosine (CPEC), targetting the de novo biosynthesis of cytidine triphosphate (CTP), increases the cytotoxicity of gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) alone and in combination with irradiation in several human tumour cells in vitro. We investigated whether CPEC enhances the therapeutic ratio of gemcitabine and irradiation in human pancreatic BxPC-3 xenografts and in rat syngeneic L44 lung tumours. These models were selected because gemcitabine and radiation are used to treat both pancreatic and lung cancer patients and both models differ in growth capacity and in gemcitabine-induced radiosensitisation. A profound dose-dependent CTP-depletion was observed after a single injection of CPEC in both tumour tissue and in normal jejunum. In both models, CPEC alone induced a slight but significant tumour growth delay. The combination of CPEC with gemcitabine, at time intervals that showed CTP-depletion after CPEC, enhanced neither tumour growth delay nor toxicity as compared to gemcitabine alone. In addition, no beneficial effect of CPEC was observed in combination with gemcitabine and radiation. These results suggest that CPEC and gemcitabine alone as well as in combination with radiation target a similar cell population in both tumour models. In conclusion, future clinical development of CPEC as a modulator of gemcitabine combined with radiation is unlikely.

Increased expression of insulin-like growth factor in intestinal lengthening by mechanical force in rats

A segment of the jejunum could double its length by the application of an axial mechanical force. We hypothesize that this growth is correlated with an increased expression of insulin-like growth factor (IGF-I) in the jejunum. Adult Sprague-Dawley rats underwent the isolation of a 1.5-cm segment of the jejunum. The isolated jejunal segment was either lengthened using mechanical force or left alone for 3 weeks. The jejunal segments were analyzed by quantitative polymerase chain reaction and immunofluorescence for the expression of IGF-I. Whereas jejunal segments that underwent isolation alone did not change their length, isolated jejunal segments that were stretched by applying a gradual mechanical force doubled their initial length. Both groups increased their muscular thickness 5 folds as compared to the normal jejunum. The mRNA level of IGF-I in the lengthened jejunum was 6 folds higher than that in the normal jejunum, but the IGF-I mRNA level in the isolated jejunum without mechanical lengthening was unchanged. By immunofluorescence, the increased IGF-I expression in the lengthened jejunum was localized to the intestinal smooth muscle cells. Insulin-like growth factor I may be an important signal induced by the applied axial force that mediates longitudinal intestinal growth.

Controlled release of basic fibroblast growth factor promotes healing of the pancreaticojejunal anastomosis: A novel approach toward zero pancreatic fistula

Several reconstructive surgical techniques have been proposed for restoring pancreatico-jejunal continuity. Little has been done, however, to evaluate the efficacy of tissue engineering on anastomotic healing. We examined the effects of basic fibroblast growth factor (bFGF) incorporated in gelatin hydrogel (GH) microspheres on the anastomotic healing of pancreaticojejunostomy. As a preliminary experiment, 20 female Wistar rats received a jejunal subserosal injection of 1 microg of bFGF-GH (n = 10), 1 microg of Free-bFGF (n = 5), or gelatin alone (n = 5) to study the effects of bFGF on the histology of normal jejunum on day 7 after the injection. Next, 12 beagle dogs received a jejunal subserosal injection of 100-microg bFGF-GH (n = 7) or gelatin alone (n = 5) at the anastomotic site of pancreaticojejunostomy. Four types of assessment were performed to compare the 2 groups: pancreatography, breaking strength test, pathologic examination, and calculation of the microvessel density (MVD). The bFGF-GH injection led to markedly increased levels of collagen and fibroblastic cellularity in the subserosal layer of the Wistar rats. In contrast, the rats treated by gelatin alone exhibited no such effects. No anastomotic failures were observed in the dogs treated by bFGF-GH. Histologic observations of this group revealed abundant granulation tissues. Treatment with bFGF-GH significantly increased the breaking strength and MVD over the levels measured in the control group (P < .01). bFGF-GH accelerates healing of pancreaticojejunal anastomosis during the early postoperative period. Basic FGF-GH may show promise as a new technique for preventing anastomotic failure of pancreaticojejunostomy.

CONTROLLED RELEASE OF BASIC FIBROBLAST GROWTH FACTOR PROMOTES HEALING OF THE PANCREATICOJEJUNAL ANASTOMOSIS

Background Several reconstructive surgical techniques have been proposed for restoring pancreatico-jejunal continuity. Little has been done, however, to evaluate the efficacy of tissue engineering on anastomotic healing. We examined the effects of basic fibroblast growth factor (bFGF) incorporated in gelatin hydrogel (GH) microspheres on the anastomotic healing of pancreaticojejunostomy. Methods As a preliminary experiment, 20 female Wistar rats received a jejunal subserosal injection of 1 μg of bFGF-GH (n = 10), 1 μg of Free-bFGF (n = 5), or gelatin alone (n = 5) to study the effects of bFGF on the histology of normal jejunum on day 7 after the injection. Next, 12 beagle dogs received a jejunal subserosal injection of 100-μg bFGF-GH (n = 7) or gelatin alone (n = 5) at the anastomotic site of pancreaticojejunostomy. Four types of assessment were performed to compare the 2 groups: pancreatography, breaking strength test, pathologic examination, and calculation of the microvessel density (MVD). Results The bFGF-GH injection led to markedly increased levels of collagen and fibroblastic cellularity in the subserosal layer of the Wistar rats. In contrast, the rats treated by gelatin alone exhibited no such effects. No anastomotic failures were observed in the dogs treated by bFGF-GH. Histologic observations of this group revealed abundant granulation tissues. Treatment with bFGF-GH significantly increased the breaking strength and MVD over the levels measured in the control group (P Conclusions bFGF-GH accelerates healing of pancreaticojejunal anastomosis during the early postoperative period. Basic FGF-GH may show promise as a new technique for preventing anastomotic failure of pancreaticojejunostomy.

Effect of partial obstruction on the contraction of guinea pig jejunum

The hypertrophied intestine proximal to an obstruction show abnormal motor function. We compared flow and inflation-induced contractions in the normal, sham-obstructed and partial obstructed guinea pig jejunum. The obstruction was created in animals living for 2, 4, 7 and 14 days with six animals in each group. Six cm jejunal segments proximal to the intervention site were immersed in an organ bath containing 37 °C aerated Krebs solutions at pH 7.4. The intestinal lumen was perfused at 0.8 ml/min. Then, the outlet was closed and ramp distension of 0–7.5 cmH2O was done. The pressure and outer diameter were recorded. Data are shown in Table. In conclusion, partial obstruction time-dependently decreased frequency and amplitude of flow-induced contractions, and increased pressure threshold and maximal amplitude of inflation-induced contractions. The study was supported by Aalborg Hospital.

Contractile Function of the Mechanically Lengthened Intestine

The application of longitudinal mechanical force induces lengthening of the small intestine. The purpose of this study is to evaluate the contractile function of the mechanically lengthened jejunum in a rodent model. Three groups of rats including normal jejunum, isolated jejunal segment without mechanical lengthening, and isolated lengthened jejunal segment, were studied for contractile function. The isometric contractions of jejunal segments were investigated in organ baths for spontaneous activity and response to potassium chloride and cholinergic carbachol. The normal control group showed a basal spontaneous activity with an average frequency of 33 +/- 0.68 contractions per min (cpm). The basal spontaneous activity for the isolated group had an average frequency of 26 +/- 2.7 cpm and for the lengthened group had an average frequency of 24 +/- 5.7 cpm. Although the normal control group had a higher frequency of basal spontaneous activity as compared to either the isolated or lengthened groups, there was no statistically significant difference between the frequencies in the isolated and the lengthened groups. All three groups demonstrated a sustained increase in tension upon administration of either potassium chloride or carbachol. The response to pharmacological stimulation, as measured by total area under the tension curve and maximal change in basal tone, was larger in the normal group than in the isolated groups. The addition of longitudinal mechanical force to lengthen the isolated jejunal segment did not further alter this change.

Distension enterogenesis: increasing the size and function of small intestine

Introduction The purpose of this study is to evaluate the feasibility of using saline infusion to lengthen small bowel while preserving intestinal enzymatic function. Methods Male Sprague-Dawley rats had a 3-cm jejunal segment taken out of continuity. A catheter was inserted in the proximal end, and the distal end was oversewn. Continuous infusion of saline into the isolated jejunal segment was started 2 weeks postoperatively. Segments were harvested 1 week later. Segment weights and lengths were measured preoperatively and at the time of harvest. Histology of harvested segments was performed. Alkaline phosphatase (ALP) and lactase assays were performed. Comparisons were made with normal jejunum from control animals. Results A 32% increase in length was achieved with saline distension of small intestine. The segment weight to length ratio was significantly increased by saline distension; however, the total protein-to-weight ratio was unchanged. Specific activities of ALP and lactase were not affected by saline distension. Because of the increased length and weight of the distended jejunal segments, total segment activities for both enzymes were significantly increased. Conclusions Saline infusion appears to be a viable method for increasing small intestinal length without compromising enzymatic function. This phenomenon may provide a new method for the treatment of patients with short bowel syndrome in the future, and further study is warranted.

Targeting normal and neoplastic tissues in the rat jejunum and colon with boronated, cationic acrylamide copolymers

A series of boronated cationic copolymers, composed of different ratios of acrylamide, N-acryloyl-3-aminophenylboronic acid and N-acryloyl-diaminoethane (the cationic moiety), were prepared with the intention of localizing boron neutron capture therapy (BNCT) in experimentally induced polyps on the luminal side of the gut of the rat. The goals of this study were to: (a) test the effect of cationization of the boronated copolymers on their uptake by polyps and normal adjacent epithelium; (b) compare the whole rat body distribution of aminophenylboronic acid (APB) and polymeric APB after local application; (c) measure the effect of micro-environmental parameters such as pH, the presence of mucin and cations on the interaction between the APB-copolymers and the epithelium of the rat intestines. Direct analysis of tissue boron levels showed that polymeric APB-uptake was higher in the colonic polyps than in the surrounding normal tissues. Free APB, however, was found in similar quantities in both. When tested in the normal jejunum and colon of the rat, polymeric APB uptake was directly proportional to the molar content of the cationic monomer in the copolymers. The presence of magnesium ions, free boron cationic monomer and mucin interfered with this uptake in a concentration-dependent manner. The uptake was pH-independent at pH 5, 7 and 10. APB accumulation in the colon polyps was inversely proportional to the cationic monomer content in the copolymers, suggesting an increased amount of mucus around the polyps, which probably impeded the electrostatic attachment of the polymer to the malignant tissue. The use polymeric APB for targeting BNCT in perioperative treatment of colorectal carcinoma is suggested, especially in the cases of microscopic residual disease after curative resection.

Substance P and vasoactive intestinal peptide in rat small-bowel isografts

Background It is established that substance P (SP) is released by stimulation of nonadrenergic noncholinergic (NANC) excitatory nerves and vasoactive intestinal peptide (VIP) by stimulation of NANC inhibitory nerves. To evaluate the function of peptidergic nerves such as SP and VIP in small-bowel isografts, we examined the enteric nerve responses to SP and VIP in the isografted rat jejunum, using the normal rat jejunum as a control. Methods Orthotopic entire small bowel transplantation (SBT) with portocaval drainage was performed from Lewis rats to Lewis rats. Grafted tissue specimens were obtained 130 days after SBT (n = 9). As controls, normal segments of the jejunum were obtained from untransplanted Lewis rats (n = 22). A mechanograph was used to evaluate in vitro jejunal responses to electrical field stimulation of the enteric nervous system before and after treatments with various autonomic nerve blockers and neuropeptides (SP and VIP). Results SP concentration-dependently mediated the contraction reaction of NANC excitatory nerve in the isografted jejunum and to a lesser extent in the normal jejunum. In addition, there were significant diferences in the percentages showing contraction at 1 × 10 −8 and 1 × 10 −6g/mL SP between the normal and isografted jejunal muscle strips ( P < .05, respectively). VIP concentration dependently mediated the relaxation reaction of NANC inhibitory nerve in the normal jejunum and to a lesser extent in the isografted jejunum. In addition, there was a significant difference between the relaxation frequencies of the normal and those of isografted jejunal muscle strips at 1 × 10 −6 g/mL SP ( P < .01). Conclusions Contraction reactions of SP were observed in both the normal and isografted jejunum but were increased in the isografted jejunum. Relaxation reactions of VIP were also observed in both the normal and isografted jejunum but were decreased in the isografted jejunum. The increase of the effects of SP via NANC excitatory nerves and the decrease of the effects of VIP in mediating NANC inhibitory nerves may be largely related to the peristaltic abnormalities seen in the isografted LEW rat jejunum.

Effect of Radiotherapy and Chemotherapy on Normal Jejunal Mucosa of Swiss Mice: Histological, Cytological, and Histochemical Studies

Radiation and Chemotherapy play a major role in the management of patients with malignant tumours, they have marked toxicity against tumour cells in addition to other undesirable side effects on normal organs. This led the researchers to carry out histological, cytological, and histochemical studies as regards the effect of radiation and chemotherapy on the jejunal mucosa of normal mice. Seventy-two male Swiss mice were used in this study. Golgi apparatus, acid phosphatase [ACP], and succinic dehydrogenase [SDH] enzymes were studied in normal jejunum as well as after exposure to radiotherapy and chemotherapy. The results revealed that prominent changes were observed in cisplatin-treated group, while more effects were shown in animals receiving combined radio and chemotherapy.