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Purpose: The objective of the present study was to investigate the effect of segmental reversal of the distal 20 cm of the small intestine in piglets with induced SBS compared to controls with SBS alone. Primary endpoint was postoperative weight change over a period of 1 month. Secondary endpoints were the influence on cell proliferation and mucosal architecture shown by histological analysis.Methods: Sixteen piglets underwent a 60% resection of the distal small intestine and were randomized into two groups. Group 1 short bowel syndrome alone (SBS) (n = 8) and group 2 with reversal of a distal small intestinal segment (SBS-RS) (n = 8). Body weight was measured daily and the pigs were euthanized after 1 month. Crypt depths, villus heights and muscle layers thicknesses were measured. For the evaluation of microvilli of the brush border of the epithelium and cell proliferation, immunohistochemical staining with Villin and Ki-67 was performed.Results: No statistically significant differences were observed concerning weight gain. Mean ± SD weight gain was 2.31 ± 2.85 kg for SBS-RS and 2.03 ± 1.27 kg for SBS (p = 0.8). In the proximal jejunal segment a significant increase in villus heights was found in the SBS group and increase in the thickness of the circular and longitudinal muscle layers in the SBS-RS group. In the distal ileal segment the longitudinal muscle layer thicknesses were increased in the SBS group. Otherwise, no significant changes were found.Conclusion: Reversal of a 20-cm distal segment showed no effect on weight gain, but there were some significant histological changes of unknown clinical significance. [ABSTRACT FROM AUTHOR]

Purpose: Intermediate filaments (IFs) are a part of the cytoskeleton that extend throughout the cytoplasm of all cells and function in the maintenance of cell-shape by bearing tension and serving as structural components of the nuclear lamina. In normal intestine, IFs provide a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. The purpose of this study was to evaluate the role of IFs during intestinal adaptation in a rat model of short bowel syndrome (SBS).Materials and Methods: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75% bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression (DGE) analysis was used to determine the cytoskeleton-related gene expression profiling. IF-related genes and protein expression were determined using real-time PCR, Western blotting and immunohistochemistry.Results: Massive small bowel resection resulted in a significant increase in enterocyte proliferation and concomitant increase in cell apoptosis. From the total number of 20,000 probes, 16 cytoskeleton-related genes were investigated. Between these genes, only myosin and tubulin levels were upregulated in SBS compared to sham animals. Between IF-related genes, desmin, vimentin and lamin levels were down-regulated and keratin and neurofilament remain unchanged. The levels of TGF-β, vimentin and desmin gene and protein were down-regulated in resected rats (vs sham animals).Conclusions: Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by a stimulated microfilaments and microtubules, and by inhibited intermediate filaments. Resistance to cell compression rather that maintenance of cell-shape by bearing tension are responsible for contraction, motility and postmitotic cell separation in a late stage of intestinal adaptation. [ABSTRACT FROM AUTHOR]

Purpose: Pediatric patients with intestinal failure need long-term parenteral nutrition (PN), but this nutritional support causes liver dysfunction, such as intestinal failure-associated liver disease (IFALD). Several studies have shown that the lipid emulsion produced by soybean oil (SO) is associated with the occurrence of IFALD. In this study, we evaluated the effect of SO and fish oil (FO) lipid emulsion on hepatic steatosis.Methods: Sprague-Dawley rats underwent jugular vein catheterization and were divided into three groups: sham operation with normal chow (Sham group), 80% small bowel resection (80% SBR) + TPN with SO lipid emulsion (SO group), and 80% SBR + TPN with FO lipid emulsion (FO group). All rats were euthanized and the serum biochemistry and hepatic histology analyzed.Results: No significant differences in the serum liver or biliary enzymes were noted between the SO and FO groups. The pathological findings and NAFLD score in the FO group did not show steatosis and were significantly lower than in the SO group. An analysis of the fatty acids profile in the both the SO and FO groups did not indicate essential fatty acid deficiency (EFAD).Conclusion: FO lipid emulsion may have a protective role against steatosis of IFALD without EFAD. [ABSTRACT FROM AUTHOR]

Purpose: The hedgehog (Hh) signaling pathway is one of the key regulators of gastrointestinal tract development. Recent studies point to the role of hedgehog signaling in regulating adult stem cells involved in maintenance and regeneration of intestinal stem cells. The purpose of this study was to evaluate the role of Hh signaling during intestinal adaptation in a rat model of short bowel syndrome (SBS).Methods: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75 % bowel resection. Parameters of intestinal adaptation, enterocyte proliferation, and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression analysis was used to determine the Hh signaling gene expression profiling. Hh-related genes and protein expression were determined using Real-Time PCR, Western blotting, and immunohistochemistry.Results: Massive small bowel resection resulted in a significant increase in enterocyte proliferation and concomitant increase in cell apoptosis. From the total number of 20,000 probes, 13 genes related to Hh signaling were investigated. In jejunum, eight genes were down-regulated, three genes up-regulated, and two genes remained unchanged. In ileum, five genes were down-regulated and six genes were unchanged in SBS vs sham animals. SBS rats also demonstrated a significant three- to fourfold decrease in SMO, GIL, and PTCH mRNA, and protein levels (determined by Real-Time PCR and Western blot) compared to control animals.Conclusion: Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by an inhibited Hh signaling pathway. Hh signaling may serve as an important mediator of reciprocal interactions between the epithelium and the underlying mesenchymal stroma during intestinal adaptation following massive bowel resection in a rat. [ABSTRACT FROM AUTHOR]

Purpose: Long-term parenteral nutrition following massive bowel resection causes liver dysfunction, such as intestinal failure-associated liver disease (IFALD). IFALD includes two different states, cholestasis and steatosis, which represents a life-threatening complication. The previous reports have shown the protective role of ghrelin in the liver. The aim of this study was to evaluate the effects of the administration of ghrelin in the liver in a parenterally fed rat model of short bowel syndrome (SBS).Methods: Rats underwent jugular vein catheterization, and were divided into three groups: 90 % small bowel resection (90 % SBR) and TPN (SBS/TPN group), 90 % SBR and TPN plus ghrelin (SBS/TPN/ghrelin group), and sham operation with normal chow (sham group). Ghrelin was administered continuously at a dose of 10 μg/kg/day. On day 13, all rats were euthanized. The serum chemistry was analyzed, the lipid content of the liver was measured, and the liver tissue was histologically analyzed.Result: The AST and LDH levels significantly increased, and the accumulation of lipids in the liver was observed in the TPN/SBS group. The accumulation of lipids in the liver of the rats in the SBS/TPN group was attenuated by the administration of ghrelin.Conclusion: The administration of ghrelin has a therapeutic potential for IFALD. [ABSTRACT FROM AUTHOR]

Purpose: Bone morphogenetic proteins (BMPs) are a group of growth factors that are implicated in intestinal growth, morphogenesis, differentiation, and homeostasis. The role of the BMP signaling cascade in stimulation of cell proliferation after massive small bowel resection is unknown. The purpose of this study was to evaluate the role of BMP signaling during intestinal adaptation in a rat model of short bowel syndrome (SBS).Methods: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75 % bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression analysis was used to determine the BMP signaling gene expression profiling. BMP-related genes and protein expression were determined using real-time PCR, Western blotting and immunohistochemistry.Results: From the total number of 20,000 probes, 8 genes related to BMP signaling were investigated. From these genes, five genes were found to be up-regulated in jejunum (BMP1-10 %, BMP2-twofold increase, BMP3-10 %, BMP2R-12 % and STAT3-28 %) and four genes to be up-regulated in ileum (BMP1-16 %, BMP2-27 %, BMP3-10 %, and STAT3-20 %) in SBS vs sham animals with a relative change in gene expression level of 10 % or more. SBS rats also demonstrated a significant increase in BMP2 and STAT3 mRNA and protein levels (determined by real-time PCR and Western blot) compared to control animals.Conclusion: Two weeks following massive bowel resection in rats, the BMP signaling pathway is stimulated. BMP signaling may serve as an important mediator of reciprocal interactions between the epithelium and the underlying mesenchymal stroma during intestinal adaptation following massive bowel resection in a rat. [ABSTRACT FROM AUTHOR]

Background: After massive bowel resection, bacterial overgrowth is frequent and favors the occurrence of Gram-negative intestinal bacterial translocation (BT). Probiotics have been recommended in several diseases and may also have beneficial effects on BT. Conversely, polymerase chain reaction (PCR) technique has shown better sensitivity than conventional methods in bacterial detection and has not been investigated in experimental models of short bowel syndrome and BT.Objective: To test the hypothesis that Bifidobacterium lactis (BL) administration decreases Escherichia coli bacterial translocation (ECBT) in experimental short bowel syndrome and to confirm the better sensitivity of PCR technique to detect ECBT.Methods: Forty-eight adult Wistar rats, orally fed with standard rat chow and tap water ad libitum, were maintained in individual metabolic cages for 10 days and divided into three groups: Control group (n = 15): non-manipulated animals. RES group (n = 15): 80% gut resection. 1 ml of sterile water was administered daily after orogastric intubation. RES-PRO group (n = 18): same resection as RES group and daily administration of 7.8 × 10(9) BL (CFU). At the end of the study, portal blood, peripheral blood and mesenteric lymph node (MLN) samples were recovered and cultured. Also, genomic DNA from E. coli was detected by PCR technique.Results: In conventional culture there was no ECBT in control animals whereas 73% of RES and 33% of RES-PRO animals showed it. PCR detected ECBT in 47, 87 and 33%, respectively, showing higher sensitivity. [ABSTRACT FROM AUTHOR]

Introduction: Transforming growth factor beta (TGF-β) has been shown to affect epithelial cell differentiation and proliferation through epithelial-mesenchymal and epithelial-immune cell interaction. In the present study, we evaluated the effect of TGF-β2-enriched polymeric diet (Modulen) on enterocyte turnover in a rat model of short bowel syndrome (SBS).Methods: Male rats were divided into four groups: Sham rats and Sham-TGF-β rats underwent bowel transection, and were treated with TGF-β from the 4th postoperative day, SBS rats underwent a 75% bowel resection, and SBS-TGF-β rats underwent bowel resection and were treated with TGF-β-enriched diet similar to Group B. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Real-time PCR was used to determine Bax and Bcl-2 mRNA expression.Results: Treatment of SBS animals with TGF-β2 supplemented diet led to a significant decrease (vs. SBS rats) in bowel weight in ileum (18%, P < 0.05), mucosal DNA content in jejunum (threefold decrease, P < 0.05) and ileum (2.5-fold decrease, P < 0.05), and mucosal protein in jejunum (twofold decrease, P < 0.05) compared to SBS-untreated animals (Group B). Treatment with TGF-β resulted in a mild decrease in enterocyte proliferation in jejunum (25%, P < 0.05) and ileum (18%, P < 0.05). A decreased cell apoptosis in the SBS-TGF-β group was accompanied by a decreased Bax and increased Bcl-2 mRNA expression.Conclusions: In a rat model of SBS, dietary TGF-β inhibits intestinal adaptation. Decreased enterocyte proliferation is responsible for this effect. [ABSTRACT FROM AUTHOR]

Purpose: It has been reported that oral insulin (OI) has a trophic effect on intestinal mucosa. In the present study, we evaluated the effect of OI on enterocyte turnover and correlated it with insulin-receptor expression along the villus-crypt axis in a rat model of short bowel syndrome (SBS).Methods: Male rats were divided into three groups: Sham rats underwent bowel transection, SBS rats underwent a 75% bowel resection, and SBS-OI rats underwent bowel resection and were treated with OI given in drinking water (1 U/ml) from the fourth postoperative day. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Real-time PCR was used to determine the level of insulin receptor-beta (IRB) mRNA. Insulin-receptor expression along the villus-crypt axis (villus tips, lateral villi and crypts) was assessed by immunohistochemistry. The effect of OI on cell turnover for each compartment was evaluated in correlation with the receptor expression. Statistical analysis was performed using the one-way ANOVA test, with P < 0.05 considered statistically significant.Results: Treatment with OI resulted in a significant increase in all parameters of intestinal adaptation. Insulin-receptor expression in crypts significantly increased in SBS rats (vs. Sham rats) and was accompanied by a significant increase in enterocyte proliferation following OI administration. A significant increase in insulin-receptor expression at the tip of the villous and in the lateral villous in SBS rats (vs. Sham) was accompanied by decreased cell apoptosis in these compartments following treatment with OI.Conclusions: In a rat model of SBS, OI enhances enterocyte turnover and stimulates intestinal adaptation. The stimulating effect of insulin on enterocyte turnover correlates with insulin-receptor expression along the villus-crypt axis. [ABSTRACT FROM AUTHOR]

Purpose: Among factors promoting intestinal adaptation after bowel resection, dietary fatty acids have a special role. The purpose of the present study was to evaluate the effects of palmitic acid (PA) on early intestinal adaptation in rats with short bowel syndrome (SBS).Materials: Male Sprague-Dawley rats underwent either a bowel transection with re-anastomosis (sham rats) or 75% small bowel resection (SBS rats). Animals were randomly assigned to one of four groups: sham rats fed normal chow (sham-NC); SBS rats fed NC (SBS-NC), SBS rats fed high palmitic acid diet (SBS-HPA), and SBS rats fed low palmitic acid diet (SBS-LPA). Rats were sacrificed on day 14. Parameters of intestinal adaptation, overall bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, cell proliferation and apoptosis were determined at sacrifice. RT-PCR and Western blotting were used to determine the level of bax and bcl-2 mRNA and protein (parameters of apoptosis), and ERK protein levels (parameter of proliferation). Statistical analysis was performed using Kruskal-Wallis test followed by post hoc test for multiple comparisons with P values of less than 0.05 considered statistically significant.Results: SBS-HFD rats demonstrated higher bowel and mucosal weight, mucosal DNA and protein in ileum, while deprivation of PA (SBS-LPA) inhibited intestinal re-growth both in jejunum and ileum compared to SBS-NC rats. A significant up-regulation of ERK protein coincided with increased cell proliferation in SBS-HFD rats (vs. SBS-NC). Also, the initial decreased levels of apoptosis corresponded with the early decrease in bax and increase in bcl-2 at both mRNA and protein levels.Conclusion: Early exposure to HPA both augments and accelerates structural bowel adaptation in a rat model of SBS. Increased cell proliferation and decreased cell apoptosis may be responsible for this effect. Deprivation of PA in the diet inhibits intestinal re-growth. [ABSTRACT FROM AUTHOR]

The main reason why enterocyte proliferative effects of peptide YY (PYY) have not been detected in rats undergoing massive small intestinal resection after feeding may have been the background activity of markedly increased endogenous PYY released from L cells in the distal gut in response to the intraluminal nutrients. The purpose of the present study was to evaluate the effects of PYY on enterocyte proliferation in a rat model of distal bowel resection (DBR) with total enteral nutrition (TEN). Male, adult Sprague-Dawley rats were assigned into three experimental groups: sham rats underwent bowel transection and reanastomosis, DBR rats underwent the resection of 40 cm distal small intestine and colon, and DBR-PYY rats underwent distal bowel resection as above, and were treated with PYY(1-36) from day 2 to day 14 postoperatively. During days 2-14 postoperatively, all animals received isocaloric TEN. At the endpoints, plasma PYY levels and parameters of enterocyte proliferation were determined. Compared with the sham group, DBR rats demonstrated a significant decrease in plasma PYY levels, and a significant increase in intestinal bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth, and crypt cell proliferation index. Administration of PYY (DBR-PYY group) led to a significant increase in plasma PYY levels, intestinal bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth, and crypt cell proliferation index in comparison with the DBR untreated group. We conclude that administration of PYY increases the plasma PYY levels, and PYY induces enterocyte proliferation with TEN after distal bowel resection. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that transforming growth factor alpha (TGF-α) enhances enterocyte proliferation and stimulates intestinal adaptation after massive bowel resection. In the present study, we evaluated the effects of TGF-α on enterocyte turnover and correlated it with epidermal-growth factor (EGF) receptor expression along the villus–crypt axis in a rat model of short bowel syndrome (SBS). Male rats were divided into three groups, sham rats underwent bowel transection (group A); SBS rats underwent a 75% bowel resection (group B); and SBS/TGF-α rats underwent bowel resection and were treated with TGF-α (75 μg/kg) (group C) from the seventh postoperative day. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Villus tips, lateral villi and crypts were separated using laser capture microdissection. EGF receptor expression for each compartment was assessed by quantitative real-time PCR (Taqman). Statistical analysis was performed using one-way ANOVA test, with P < 0.05 considered statistically significant. Treatment with TGF-α resulted in a significant increase in all parameters of intestinal adaptation. EGF receptor expression in crypts significantly increased in SBS rats (vs sham rats) (0.035 ± 0.013 vs 0.010 ± 0.002 Log ng Total RNA/18 s) and was accompanied by a significant increase in enterocyte proliferation (169 ± 8 vs 138 ± 5 BrdU positive cells/per 10 crypts, P < 0.05) and decreased apoptosis following TGF-α administration (group C). A significant decrease in EGF receptor expression at the tip of the villus (0.005 ± 0.002 vs 0.029 ± 0.014 Log ng Total RNA/18 s) and in the lateral villus (0.003 ± 0.001 vs 0.028 ± 0.006 Log ng Total RNA/18 s) in SBS (group B) rats (vs sham, group A) was accompanied by increased cell apoptosis in these compartments following treatment with TGF-α (group C). In a rat model of SBS, TGF-α increased enterocyte proliferation and stimulated intestinal adaptation. The effect of TGF-α on enterocyte turnover is correlated with EGF receptor expression along the villus–crypt axis. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that the adipose tissue-derived cytokine leptin (LEP) is involved in modulation of growth and differentiation of normal small intestine. The purpose of the present study was to evaluate the effects of parenteral LEP on structural intestinal adaptation, cell proliferation and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and re-anastomosis, SBS-rats underwent a 75% small bowel resection, and SBS-LEP-rats underwent bowel resection and were treated with LEP given subcutaneously at a dose of 20 μg/kg, once daily, from day 3 through 14. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height and crypt depth in jejunum and ileum), enterocyte proliferation and enterocyte apoptosis were determined on day 15 following operation. Ileal tissue samples were taken for detection of bax and bcl-2 gene expression using RT-PCR technique. Statistical analysis was performed using the non-parametric Kruskal–Wallis ANOVA test, with P<0.05 considered statistically significant. Treatment with subcutaneous LEP resulted in a significant increase in jejunal (17%, P<0.05) and ileal (13%, P<0.05) bowel weight, jejunal (10%, P<0.05) and ileal (25%, P<0.05) mucosal weight, jejunal (26%, P<0.05) and ileal (38%, P<0.05) mucosal DNA, ileal (25%, P<0.05) mucosal protein, jejunal (41%, P<0.05) and ileal (21%, P<0.05) villus height, jejunal (37%, P<0.05) crypt depth, and jejunal (24%, P<0.05) and ileal (21%, P<0.05) enterocyte proliferation compared to SBS-animals. Enterocyte apoptosis increased significantly after bowel resection in jejunum and ileum compared to sham animals and was accompanied by an increased bax gene expression and a decreased bcl-2 gene expression in ileal samples. SBS-LEP rats showed a trend toward a decrease in enterocyte apoptosis in ileum and a mild decrease in bax gene expression compared to SBS-untreated animals. In conclusion, in a rat model of SBS parenteral LEP stimulates structural intestinal adaptation. Increased cell proliferation and decreased cell death via apoptosis may be responsible for this increased cell mass. [ABSTRACT FROM AUTHOR]

Massive small bowel resection (SBR) results in a significant increase in intestinal epithelial cell (EC) proliferation as well as apoptosis. Because the site of SBR (proximal (P) vs. distal (D)) affects the degree of intestinal adaptation, we hypothesized that different rates of EC apoptosis would also be found between P-SBR and D-SBR models. Wild-type C57BL/6J mice underwent: (1) 60% P-SBR, (2) 60% D-SBR, or (3) SHAM-operation (transaction-reanastomosis) at the mid-gut point. Mice were sacrificed after 7 days. EC apoptosis was measured by TUNEL staining. EC-related apoptotic gene expression including intrinsic and extrinsic pathways was measured with reverse transcriptase-polymerase chain reaction. Bcl-2 and bax protein expression were analyzed by Western immunoblotting. Both models of SBR led to significant increases in villus height and crypt depth; however, the morphologic adaptation was significantly higher after P-SBR compared to D-SBR (P<0.01). Both models of SBR led to significant increases in enterocyte apoptotic rates compared to respective sham levels; however, apoptotic rates were 2.5-fold higher in ileal compared to jejunal segments (P<0.01). P-SBR led to significant increases in bax (pro-apoptotic) and Fas expression, whereas D-SBR resulted in a significant increase in TNF-alpha expression (P<0.01). EC apoptosis seems to be an important component of intestinal adaptation. The significant difference in EC apoptotic rates between proximal and distal intestinal segments appeared to be due to utilization of different mechanisms of action. [ABSTRACT FROM AUTHOR]

Intestinal adaptation is the most important event in short bowel syndrome following a massive small bowel resection. Effects of various growth factors and their synergism have been well documented in intestinal adaptation. This study aimed to compare the effect of two different trophic agents, epidermal growth factor (EGF) and bombesin (BBS), on intestinal adaptation following massive intestinal resection. Sprague-Dawley male rats were assigned to one of four groups after a 75% small bowel resection. Either EGF (90 microg/kg), BBS (10 microg/kg), EGF+BBS, or bovine serum albumin (BSA) were injected subcutaneously three times a day. The animals were killed 10 days after the operation. Weight loss and morphologic parameters such as mucosal thickness, villus height, crypt depth, villus-to-crypt ratio, and muscularis propria height were measured. In the EGF+BBS group, mucosal thickness was found to be significantly increased compared with the other study groups (p<0.05). Similarly, villus height was significantly increased only in the EGF+BBS group (p<0.05). In the BBS group, both villus height and mucosal thickness showed a slight increase, but the values were not statistically significant compared with the vehicle-treated group. There were no significant differences in any of the remaining parameters between the groups. The results of this study indicate that the gut hormones EGF and BBS act synergistically in facilitating the adaptive response of the remnant ileum to massive intestinal resection. [ABSTRACT FROM AUTHOR]

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal structure and absorptive function. It is also well known that the route of administration modulates the effects of ARG. The present study evaluated the effects of parenteral ARG on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-ARG rats underwent a 75% small bowel resection and were treated with ARG given subcutaneously at a dose of 300 mug/kg, once daily, from days 3 to 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. The SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. The SBS-ARG animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth compared with SBS animals. The SBS-ARG rats also had a lower cell proliferation index in both jejunum and ileum and a greater enterocyte apoptotic index in ileum compared with the SBS-untreated group. In conclusion, in a rat model of SBS, parenteral arginine inhibits structural intestinal adaptation. Decreased cell proliferation and increased apoptosis are the main mechanisms responsible for decreased cell mass. [ABSTRACT FROM AUTHOR]

Insulin has been shown to influence intestinal structure and absorptive function. The purpose of the present study was to evaluate the effects of parenteral insulin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-INS rats underwent a 75% small bowel resection and were treated with insulin given subcutaneously at a dose of 1 U/kg, twice daily, from day 3 through day 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. SBS-INS animals demonstrated higher jejunal and ileal bowel and mucosal weights, jejunal and ileal mucosal DNA and protein, and jejunal and ileal crypt depth compared with SBS animals. SBS-INS rats also had a greater cell proliferation index in both jejunum and ileum and a trend toward a decrease in enterocyte apoptotic index in jejunum and ileum compared with the SBS untreated group. In conclusion, parenteral insulin stimulates structural intestinal adaptation in a rat model of SBS. Increased cell proliferation is the main mechanism responsible for increased cell mass. [ABSTRACT FROM AUTHOR]

Among factors promoting mucosal hyperplasia after bowel resection, long-chain fatty acids may have a special role. The purpose of the present study was to evaluate the effects of high-fat diet (HFD) on early intestinal adaptation in rats with short bowel syndrome (SBS). Male Sprague-Dawley rats underwent either a bowel transection with re-anastomosis (Sham rats) or 75% small bowel resection (SBS rats). Animals were randomly assigned to one of three groups: Sham rats fed normal chow (Sham-NC); SBS rats fed NC (SBS-NC); and SBS rats fed HFD (SBS-HFD). Rats were killed on days 3 or 14. Body weight and parameters of intestinal adaptation (overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth) were determined at time of killing. By day 3, SBS-HFD rats demonstrated higher duodenal and jejunal bowel and mucosal weights and ileal villus height and jejunal crypt depth vs SBS-NC rats. By day 14 SBS-HFD rats continued to demonstrate increased duodenal and jejunal bowel weight and duodenal mucosal weight vs SBS-NC animals. We conclude that early exposure to HFD both augmented and accelerated structural bowel adaptation in a rat model of SBS. [ABSTRACT FROM AUTHOR]

Short bowel syndrome (SBS) can occur after extensive intestinal resections. In SBS, the aim of surgical techniques is to prolong intestinal transit time (ITT) and to increase the absorptive surface. This experimental study was conducted to research the effect of extramucosal intestinal plication on ITT in rats. Thirty Sprague-Dawley rats were divided into three groups. In the control group, barium solution was administrated by gavage. Forty-five minutes later, the rats were sacrificed, and the total length of their small bowels (SBs) and the distance of the barium in the SBs were measured. The ratio of the distance of the barium to the length of the SB was calculated, and the ITT was found for normal rats. Intestinal plication (made with three seromuscular sutures at the same level: one on the antimesenteric side, and two on the lateral sides of the bowel) and laparotomy and bowel manipulation were carried out in the study and sham groups, respectively, and ITT was measured by the same method after 1 week. A one-way ANOVA test was used to compare the groups in terms of body weight, total length of the SB, distance of the barium in the SB, and the ratio of this distance to the length of the SB. The rats were statistically homogeneous in terms of body weight and total length of the SB ( p >0.05). The distances of the barium in the small bowel in the control, sham, and study groups were 73.4±8.5 cm, 77.5±6.8 cm, and 56.3±3.6 cm, respectively. The distances of barium in the SB in the study group were statistically shorter than in the other groups ( p <0.05). The ratios of the distance of the barium to the length of the SB in the control, sham, and study groups were 65.8±7.3, 66.4±4.5, and 49.9±3.8, respectively. In the study group, this ratio was also statistically lower than in the other groups ( p <0.05). Extramucosal intestinal plication retarded ITT significantly in the study group compared with the other groups. This technique does not entail any risk of morbidity and mortality; therefore, it can be used in the treatment of SBS. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of dietary fat on the time course of changes in fat absorption and tissue and plasma lipid composition in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats underwent either a bowel transection with re-anastomosis (Sham rats) or 75% small bowel resection (SBS rats). Animals were randomly assigned to one of three groups: Sham rats fed normal chow (Sham-NC), SBS rats fed normal chow (SBS-NC), or SBS rats fed a high-fat diet (SBS-HFD). Rats were sacrificed on day 3 or 14. Body weight, food intake, food clearance (dry fecal mass), and fat clearance (total fecal fat) were measured twice a week. Fat and energy intakes were calculated according to the amount of ingested food. Food and fat absorbability were calculated as intake minus clearance and were expressed as percent of intake. Serum cholesterol, triglyceride, and albumin were measured. Total lipid composition of the liver, epididymal adipose tissue, and the small intestine was determined. Statistical analysis was performed by a Student’s test, with p values <0.05 considered significant. Both food and fat absorbability diminished after bowel resection in rats fed NC. This was accompanied by a decrease in body weight gain, plasma triglyceride and protein levels, and total lipid content of the liver at day 3 and of a decrease in adipose tissue at day 14 following operation. SBS-HFD rats experienced a significant increase ( p <0.05) in food absorbability after 7 days and fat absorbability after 3 days compared with Sham-NC and SBS-NC rats ( p <0.05), as well as increases in serum cholesterol, triglycerides, and glucose compared with SBS-NC rats. On day 14, plasma lipid levels in SBS-HFD rats were not different from SBS-NC or control rats; however, albumin levels were higher. A high-fat diet increased total fat content of the liver early after operation. In conclusion, in a rat model of SBS, an early high-fat diet increased the absorptive capacity of the intestinal remnant as seen by increased food and fat absorbability. These findings suggest a benefit of a high-fat diet on intestinal adaptation in general and on lipid absorption in particular. [ABSTRACT FROM AUTHOR]

Introduction: After successful experimental autologic-allotopic ileum mucosa transplantation, we investigated the remodeling of the transplanted submucous and mucous plexus, which is essential for the motility of the created colon coat-ileum mucosa complex.Method: In 8 beagles we transplanted ileum mucosa in a demucosed vascularized transverse colon segment, which was reanastomosed with the small bowel immediately after transplantation. Four weeks later the animals were sacrificed and histology specimens taken from the anastomosis site of the colon coat-ileum mucosa complex, allowed comparison between transplanted and normal mucosa in the same section. After fixation in 4% formaldehyde and PBS the samples were embedded in paraffin and 7 micro m sections were prepared. The distribution of nerve fibers and submucous ganglia were examined in dewaxed sections, using antisera against protein gene product (PGP9.5), a general neuronal marker.Results: The submucosal ganglia were prominent in all samples but they were smaller and the submucous nerve cells within the ganglia were less numerous compared to the controls. The innervation of the transplanted ileum mucosa was reduced as the number of nerve fibers in the mucosal villi was decreased. Besides these neuromorphologic changes the transplanted mucosa showed a slightly higher rate of shortened villi compared to normal ileum mucosa.Conclusions: After ileum mucosa transplantation the submucosal ganglia are smaller and less numerous. Furthermore there is a considerable loss of nerve fibers in the mucosal layer. Additionally a loss of microvilli in the transplanted ileum mucosa was found. Whether these findings represent a state of remodeling or a slow atrophy of the enteric nervous system in the transplanted areas is currently under investigation. [ABSTRACT FROM AUTHOR]

Introduction: Since a standard therapy for short bowel syndrome does not yet exist, every search for new surgical methods would be worthwhile. In previous studies we could show that autologous-allotopic ileum mucosa transplantation is feasible. After a modification of our technique a vascularized colon muscle coat lined completely with transplanted ileum mucosa could be engendered.Method: In 12 young beagles autologous ileum mucosa was transplanted in a demucosed vascularized transverse colon segment. The colon coat-ileum mucosa complex was anastomosed with the small bowel immediately after transplantation, 4 weeks later the animals were sacrificed and histology specimens were harvested from the colon coat-ileum mucosa complex, normal ileum and normal colon. After fixation in 2.5% glutaraldehyde the samples were frozen (-40 degrees C) and 14 micro m sections were stained with hemalaun and eosin. The lumen diameter, the mucosa, submucosa and colon muscle coat thickness, as well as the mucosal crypt depth were evaluated.Results: The diameter of the colon coat-ileum mucosa-complex was smaller than the diameter of normal ileum and colon with no significant stenosis. There were no marked differences in thickness of mucosa and depth of the mucosal crypts compared to the controls, but the transplanted mucosa showed a slightly higher rate of shortened villi. The submucosal layer was thicker following transplantation and showed good neovascularization. The circular muscle layer of the transplanted colon coat was up to 178% thicker and the thickness of the transplanted longitudinal muscle layer differed between 58% and 143% in comparison to normal colon.Conclusions: Only a few histologic differences between transplanted and normal ileum mucosa could be observed after autologous-allotopic ileum mucosa transplantation. Therefore a nearly normal function of the colon coat-ileum mucosa complex has to be expected. Long term experiments of the histologic changes as well as further functional studies are on-going in order to finally apply autologous-allotopic ileum mucosa transplantation clinically. [ABSTRACT FROM AUTHOR]

Background: The intestinal adaptive response [increased epithelial cell (EC) proliferation and apoptosis] after massive small bowel resection (SBR) is partially controlled by intraepithelial lymphocytes (IEL). To identify IEL factors contributing to EC adaptation post-SBR we utilized microarray assays.Methods: Mice underwent a 70% SBR (SBR1w/SBR4w) or sham operation (Sham1w/Sham4w). After 1 or 4 weeks (1w, 4w) small bowel was harvested, and IEL isolated. Determination of the EC-proliferation rate used BrdU incorporation, and of the EC-apoptotic rate used Annexin V staining. Affymetrix system microarrays (12,491 genes) were performed to examine IEL-mRNA expression. Results were considered significant if fold-change (FC) between groups was >2 and P<0.05 (F-test), or FC>3 and 0.05> P >0.01, or FC>4 and P>0.05. Significant genes were confirmed by conventional RT-PCR.Results: The SBR EC-proliferation rate increased significantly in both 1w and 4w groups compared to Sham: SBR1w 0.24+/-0.07 vs. Sham1w 0.12+/-0.02 (P=0.03); SBR4w 0.35+/-0.04 vs. Sham4w 0.19+/-0.02 ( P<0.01). The EC-apoptotic rate was unchanged in the 1w group, but significantly differed from controls after 4 weeks: SBR4w 39.92+/-6.78 vs. Sham4w 12.56+/-6.44 ( P<0.01). Microarray results were analyzed to identify potential growth-modifying IEL genes. The following were identified (function in parenthesis; A, apoptosis; P, proliferation): lipocalin 2 (promotes A), angiotensin converting enzyme (increases A), Rap2 interacting protein (reduces A, promotes P), amphiregulin (promotes P) and leucine-rich-alpha2-glycoprotein (promotes A, reduces P). Based on RT-PCR results these genes showed significant changes between groups. The increase in ACE at 1w preceded the observed apoptotic changes. The alterations in lipocalin 2, Rap2 and amphiregulin at 4w coincided with the marked changes in growth and apoptosis in the SBR mice.Conclusions: IEL undergo temporal changes after SBR. These findings provide profound insight into potential IEL-dependent regulation of EC homeostasis post-SBR. [ABSTRACT FROM AUTHOR]

Purpose: This study compared laparoscopy-assisted stoma closure (Lap) with conventional closure (Co) to assess loss of intestine.Methods: Ileostomies (loop L; single S) were performed 5 cm proximal to the ileocecal junction through a right lower quadrant incision in forty 11-week-old Lewis rats (L = 20, S = 20). Stoma closure was performed 60 days later using laparoscopy (Lap) or conventional closure (Co) in 10 rats each, to give 4 groups, Lap-L, Lap-S, Co-L, and Co-S. End-to-end anastomosis was performed through the stoma site in all rats. Bowel resected from the skin to the anastomosis was termed resected unusable bowel (RUB) and measured blindly. Laparotomy was performed 30 days later to assess the status of the anastomosis and complications.Results: Average RUB with Lap was significantly shorter; Lap-L (17.8 mm) versus Co-L (23.8 mm), P = 0.002, and Lap-S (10.6 mm) versus Co-S (13.8 mm), P = 0.001. During Co, accidental full-thickness injury to underlying bowel during stoma take-down occurred in 3 Co-L and 2 Co-S rats. All Lap rats were uncomplicated. Average times taken until end of stoma take-down were 6.1 min for Lap-L (3.2 min for trocar insertion, 2.8 min for stoma take-down), 5.6 min for Lap-S (2.8 and 2.7 min), 6.3 min for Co-L (from first incision to stoma take-down), and 5.1 min for Co-S (P = NS). At laparotomy there was no evidence of complications such as wound infection, incisional hernia or anastomotic stenosis in any rat.Conclusions: Our results suggest that laparoscopy-assisted stoma closure is safe and quick, and results in less loss of intestine during stoma closure. [ABSTRACT FROM AUTHOR]