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1.  Effect of intestinal resection on human small bowel motility. 
Gut  1996;38(6):859-863.
BACKGROUND: Few data are available on adaptive changes of human small bowel motility after intestinal resection. AIM: To characterise jejunal motility after extensive and limited distal intestinal resection. METHODS: Seven patients with a short bowel syndrome after total ileal and partial jejunal resection (residual jejunal segments between 60 and 100 cm) and six patients with limited distal ileal resection (resected segment between 30 and 70 cm) underwent ambulatory 24 hour jejunal manometry 15 (6-24) months after the operation. Normal values were obtained from 50 healthy subjects. Fasting motility and the motor response to a 600 kcal solid meal were analysed visually and by a computer program. RESULTS: Limited ileal resection did not result in changed jejunal motility. After extensive distal resection, patients had a significantly shorter migrating motor complex (MMC) cycle and a significantly shorter duration of the postprandial motor response compared with controls (p < 0.005). Intestinal resection had no influence on jejunal contraction frequency and amplitude and did not lead to any abnormal motor pattern. CONCLUSION: Extensive distal resection of the small intestine produces distinct abnormalities of fasting and postprandial motility in the intestinal remnant. The shortening of digestive motility and the increased frequency of MMC cycling could contribute to malabsorption and diarrhoea in the short bowel syndrome.
PMCID: PMC1383193  PMID: 8984024
2.  Growth Factors: Possible Roles for Clinical Management of the Short Bowel Syndrome 
Seminars in pediatric surgery  2010;19(1):35-43.
The structural and functional changes during intestinal adaptation are necessary to compensate for the sudden loss of digestive and absorptive capacity after massive intestinal resection. When the adaptive response is inadequate, short bowel syndrome (SBS) ensues and patients are left with the requirement for parenteral nutrition and its associated morbidities. Several hormones have been studied as potential enhancers of the adaptation process. The effects of growth hormone (GH), insulin-like growth factor-1, epidermal growth factor and glucagon-like peptide-2 (GLP-2) on adaptation have been studied extensively in animal models. In addition, GH and GLP-2 have shown promise for the treatment of short bowel syndrome in clinical trials in humans. Several lesser studied hormones, including leptin, corticosteroids, thyroxine, testosterone and estradiol, are also discussed.
PMCID: PMC2891767  PMID: 20123272
growth factor; adaptation; enterocyte; mucosa; proliferation
3.  Colonic GLP-2 is not Sufficient to Promote Jejunal Adaptation in a PN-Dependent Rat Model of Human Short Bowel Syndrome 
Bowel resection may lead to short bowel syndrome (SBS), which often requires parenteral nutrition (PN) due to inadequate intestinal adaptation. The objective of this study was to determine the time course of adaptation and proglucagon system responses after bowel resection in a PN-dependent rat model of SBS.
Rats underwent jugular catheter placement and a 60% jejunoileal resection + cecectomy with jejunoileal anastomosis or transection control surgery. Rats were maintained exclusively with PN and killed at 4 hours to 12 days. A nonsurgical group served as baseline. Bowel growth and digestive capacity were assessed by mucosal mass, protein, DNA, histology, and sucrase activity. Plasma insulin-like growth factor I (IGF-I) and bioactive glucagon-like peptide 2 (GLP-2) were measured by radioimmunoassay.
Jejunum cellularity changed significantly over time with resection but not transection, peaking at days 3–4 and declining by day 12. Jejunum sucrase-specific activity decreased significantly with time after resection and transection. Colon crypt depth increased over time with resection but not transection, peaking at days 7–12. Plasma bioactive GLP-2 and colon proglucagon levels peaked from days 4–7 after resection and then approached baseline. Plasma IGF-I increased with resection through day 12. Jejunum and colon GLP-2 receptor RNAs peaked by day 1 and then declined below baseline.
After bowel resection resulting in SBS in the rat, peak proglucagon, plasma GLP-2, and GLP-2 receptor levels are insufficient to promote jejunal adaptation. The colon adapts with resection, expresses proglucagon, and should be preserved when possible in massive intestinal resection.
PMCID: PMC3631543  PMID: 19644131
intestinal failure; intestinal adaptation; GI hormones; short bowel syndrome; bowel resection
4.  Effect of cholera toxin on ileal water and solute transport after resection of the proximal small intestine in the rat. 
Gut  1981;22(11):953-957.
Intestinal adaptation after extensive small bowel resection results in mucosal hypertrophy and an increased capacity of the remaining small intestine to absorb solutes and water. We tested the ability of the adapted rat ileum to respond to a secretory stimulus, cholera toxin. Six weeks after 50% jejunal resection (short gut) or sham operation water and solute transport were measured in a 16 cm segment of ileum before and after exposure to cholera toxin in a single pass in vivo perfusion system. During the control periods absorption of glucose, acetate and water per unit length of intestine was significantly greater in short gut animals (P less than 0.05 to 0.001). After exposure to cholera toxin absorption of glucose and acetate was significantly reduced in both groups (P less than 0.05 to 0.01). Sodium and chloride secretion and net change in water movement in response to cholera toxin were significantly greater (P less than 0.05 to 0.01) in short gut animals. Generally the differences between short gut and sham operation animals disappeared when the data were normalised for mucosal weight. Chloride secretion per gram mucosa was less in short gut animals (P less than 0.001). The data indicate that the adapted small bowel is not only capable of enhanced absorption but also of enhanced net secretion in response to cholera toxin. The changes reflect the increased number of enterocytes per unit length of intestine after intestinal adaptation.
PMCID: PMC1419464  PMID: 7308849
5.  Distraction induced Enterogenesis: A unique mouse model using polyethylene glycol 
The Journal of surgical research  2011;170(1):41-47.
Recent studies have demonstrated that the small intestine can be lengthened by applying mechanical forces to the bowel lumen – distraction-induced enterogenesis. However, the mechanisms which account for this growth are unknown, and might be best examined using a mouse model. The purpose of this study is to establish the feasibility of developing distractive-induced small bowel growth in mouse.
12-week old C57BL/6J mice had a jejunal segment taken out of continuity, and distended with polyethylene glycol (PEG: 3350 KDa); this group was compared to a control group without stretching. Segment length and diameter were measured intra-operatively and after 5 days. Villus height, crypt depth, muscle thickness in the isolated segment were assessed. Rate of epithelial cell proliferation (5-bromo-2-deoxyuridine: BrdU incorporation) in crypt was also examined. The mucosal mRNA expression of targeted factors were performed to investigate potential mechanisms of which might lead to distraction-induced enterogenesis.
At harvest, the PEG-stretch group showed a significant increase in length and diameter versus controls. Villus height, crypt depth and muscular layer thickness increased in the PEG group. The PEG group also showed significantly increased rates of epithelial cell proliferation versus controls. Real-time PCR showed a trend toward higher β-catenin and c-myc mRNA expression in the PEG stretched group; however, this difference was not statistically significant.
Radial distraction-induced enterogenesis with PEG is a viable method for increasing small intestinal length and diameter. This model may provide a new method for studying the mechanisms leading to distraction-induced enterogenesis.
PMCID: PMC3154514  PMID: 21605872
short bowel syndrome; distraction-induced enterogenesis; polyethylene glycol; proliferation; intestinal morphology
6.  Proximal enterectomy provides a stronger systemic stimulus to intestinal adaptation than distal enterectomy. 
Gut  1987;28(Suppl):165-168.
Enteroglucagon has been implicated as a tropic hormone in the control of intestinal adaptation. Because cells producing enteroglucagon are located mainly in the distal small bowel (and colon), ileal resection might be expected to produce less adaptive change than a jejunal resection of equivalent length. This hypothesis was tested in male Sprague-Dawley rats (n = 40) weighing 184.0 +/- 7.3 g and receiving a Thiry-Vella fistula (TVF) of the mid-60% of the small intestine. One group had concomitant resection of the jejunum proximal to the TVF (n = 12), another had resection of the ileum distal to the TVF (n = 13), while controls had a TVF alone (n = 15). When killed 10 days postoperatively rats with ileal resection weighed only 81% of controls (p less than 0.001) and 85% of those with jejunal resection (p less than 0.01). Jejunal resection produced an 81% increase in crypt cell production rate (measured by a stathmokinetic technique) over control values (28.5 +/- 4.2 v 15.8 +/- 2.3 cells/crypt/h: p = 0.025), whereas ileal resection had no demonstrable effect (17.5 +/- 2.3 cells/crypt/h). Adaptive hyperplasia in isolated small bowel is modulated by factors localised to the distal small intestine, enteroglucagon being a plausible candidate.
PMCID: PMC1434573  PMID: 3692304
7.  Complicated jejunal diverticulosis: A case report with literature review 
Jejunal diverticuli are rare and usually asymptomatic. More commonly, they are seen as incidental findings on CT images, enteroclysis, or during surgery. Complications such as bleeding, perforation, obstruction, malabsorption, diverticulitis, blind loop syndrome, volvulus, and intussusceptions may warrant surgical intervention.
Case report:
We report a case of 47-year old woman who had suffered from intestinal obstruction for 3 days. The symptoms did not improve after conservative treatment. An exploratory laparotomy found small bowel obstruction due to proximal jejunal diverticulum with an adhesion epiploic band. Strangulation of the jejunum resulted from the internal hernia caused by the band. The band was removed and the proximal jejunum segmentally resected. The postoperative course was uneventful.
Although this phenomenon is rare, we should keep in mind that intestinal diverticulosis may induce intestinal obstructions of different kinds, repeat physical examinations and X-ray films are needed and enteroclysis studies or CT scan are helpful in diagnosis. Surgery is indicated for acute abdominal or repeated intestinal obstruction.
PMCID: PMC3364665  PMID: 22666695
Jejunal diverticula; gastrointestinal obstruction; jejunal resection
8.  Intestinal hormones and growth factors: Effects on the small intestine 
There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In partI, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part II will detail the effects of glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids.
PMCID: PMC2653359  PMID: 19152442
Epidermal growth factor; Glucocortico-steroids; Insulin-like growth factor-I/II; Intestinal growth; Transforming growth factor-α-2; Hepatocyte growth factor; Keratinocyte growth factor
9.  Mechanical Extension Implants for Short-Bowel Syndrome 
Short-bowel syndrome (SBS) is a rare, potentially lethal medical condition where the small intestine is far shorter than required for proper nutrient absorption. Current treatment, including nutritional, hormone-based, and surgical modification, have limited success resulting in 30% to 50% mortality rates. Recent advances in mechanotransduction, stressing the bowel to induce growth, show great promise; but for successful clinical use, more sophisticated devices that can be implanted are required. This paper presents two novel devices that are capable of the long-term gentle stressing. A prototype of each device was designed to fit inside a short section of bowel and slowly extend, allowing the bowel section to grow approximately double its initial length. The first device achieves this through a dual concentric hydraulic piston that generated almost 2-fold growth of a pig small intestine. For a fully implantable extender, a second device was developed based upon a shape memory alloy actuated linear ratchet. The proof-of-concept prototype demonstrated significant force generation and almost double extension when tested on the benchtop and inside an ex-vivo section of pig bowel. This work provides the first steps in the development of an implantable extender for treatment of SBS.
PMCID: PMC1828127  PMID: 17369875
Shape Memory Alloy; Medical Implant; Short Bowel Syndrome; Extension; SMA ratchet
10.  Intestinal Adaptation for Oligopeptide Absorption via PepT1 After Massive (70%) Mid Small Bowel Resection 
Proteins are absorbed primarily as short peptides via PepT1.
Intestinal adaptation for peptide absorption after massive mid-small intestinal resection occurs by increased expression of PepT1 in the remnant small intestine and colon.
Peptide uptake was measured in duodenum, jejunum, ileum, and colon using Glycyl-Sarcosine 1 wk (n=9) and 4 wk (n=11) after 70% mid-small bowel resection, and in corresponding segments from unoperated rats (n=12) and after transection and reanastomosis of jejunum and ileum (n=8). Expression of PepT1 (mRNA, protein) and villus height were measured.
Intestinal transection/reanastomosis did not alter gene expression. Compared to non-operated controls, 70% mid-small bowel resection increased jejunal peptide uptake (p<0.05) associated with increased villus height (1.13 vs 1.77 and 1.50 mm resp, p<0.01). In ileum although villus height increased at 1 and 4 wk (1.03 vs 1.21 and 1.35 mm resp; p<0.01), peptide uptake was not altered. PepT1 mRNA and protein were decreased at 1 wk, and PepT1 protein continued low at 4 wk. Gene expression, peptide uptake, and histomorphology were unchanged in the colon.
Jejunal adaptation for peptide absorption occurs by hyperplasia. Distal Ileum and colon do not have a substantive role in adaptation for peptide absorption.
PMCID: PMC3050655  PMID: 21170601
Peptide absorption; short bowel syndrome; PepT1; intestinal adaptation; protein absorption; malabsorption
11.  Distraction-induced intestinal enterogenesis: Preservation of intestinal function and lengthening after re-implantation into normal jejunum 
Annals of Surgery  2012;255(2):302-310.
Significant bowel lengthening can occur in an isolated intestinal segment with the use for linearly directed distractive forces; resulting in increased surface area and epithelial cell proliferation. We hypothesized that re-implantation 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 segment were then re-implanted into normal intestinal continuity. Pigs were studied after another 28days. 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 re-implantation. Motility after re-implantation was similar to non-operated pigs. Barrier function, mucosal disaccharidase levels and electrophysiologic measures declined immediately after lengthening, but returned to nearly normal levels 28 days after re-implantation.
Bowel lengthening results in a transient decline in mucosal absorptive function and smooth muscle contractility. However, function approaches that of normal bowel after re-implantation 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.
PMCID: PMC3259228  PMID: 21997804
12.  Success of microvascular surgery; repair mesenteric injury and prevent short bowel syndrome: a case report 
Superior mesenteric injury is a rare entity but when it occurs, short bowel syndrome is one of the uninvited results of the emergency surgical procedures.
Case presentation
We present a 19-year-old boy with blunt abdominal trauma which caused serious mesenteric injury. Because ultrasound revealed free intraabdominal fluid, he underwent emergency laparotomy. Adequate vascularization of approximately 20 cm of proximal jejunal segment and approximately 20 cm of terminal ileum was observed. Nevertheless, the mesentery of the rest of the small intestine segments was ruptured completely. We performed an end-to-end anastomosis between a distal branch of the superior mesenteric artery in the mesentery of the ileal segment and a branch of the superior mesenteric artery using separate sutures of 7.0 monofilament polypropylene. The patient's gastrointestinal passage returned to normal on the postoperative day 2. He recovered without any complication and was discharged from hospital on the postoperative day seven.
In this case report, we emphasize the importance of preservation of injured mesenteric artery due to abdominal trauma which could have resulted in short bowel syndrome.
PMCID: PMC2000873  PMID: 17697360
13.  Gastrointestinal hormones in short bowel syndrome. Peptide YY may be the 'colonic brake' to gastric emptying. 
Gut  1996;39(2):267-272.
BACKGROUND: Short bowel patients with a jejunostomy have large volume stomal outputs, which may in part be due to rapid gastric emptying of liquid. Short bowel patients with a preserved colon do not have such a high stool output and gastric emptying of liquid is normal. AIMS: To determine if differences in the gastric emptying rate between short bowel patients with and without a colon can be related to gastrointestinal hormone changes after a meal. SUBJECTS: Seven short bowel patients with no remaining colon (jejunal length 30-160 cm) and six with jejunum in continuity with a colon (jejunal length 25-75 cm), and 12 normal subjects. METHODS: The subjects all consumed a 640 kcal meal; blood samples were taken for 180 minutes for measurement of gastrointestinal hormones. RESULTS: Patients with a colon had high fasting peptide YY values (median 71 pmol/l with a colon; 11 pmol/l normal subjects, p < 0.005) with a normal postprandial rise, but those without a colon had a low fasting (median 7 pmol/l, p = 0.076) and a reduced postprandial peptide YY response (p < 0.050). Motilin values were high in some patients without a colon. In both patient groups fasting and postprandial gastrin and cholecystokinin values were high while neurotensin values were low. There were no differences between patient groups and normal subjects in enteroglucagon, pancreatic polypeptide, or somatostatin values. CONCLUSIONS: Low peptide YY values in short bowel patients without a colon may cause rapid gastric emptying of liquid. High values of peptide YY in short bowel patients with a retained colon may slow gastric emptying of liquid and contribute to the "colonic brake'.
PMCID: PMC1383310  PMID: 8977342
14.  Resistin-Like Molecule-β Inhibits SGLT-1 Activity and Enhances GLUT2-Dependent Jejunal Glucose Transport 
Diabetes  2009;58(9):2032-2038.
An increased expression of RELM-β (resistin-like molecule-β), a gut-derived hormone, is observed in animal models of insulin resistance/obesity and intestinal inflammation. Intestinal sugar absorption is modulated by dietary environment and hormones/cytokines. The aim of this study was to investigate the effect of RELM-β on intestinal glucose absorption.
Oral glucose tolerance test was performed in mice and rats in the presence and the absence of RELM-β. The RELM-β action on glucose transport in rat jejunal sacs, everted rings, and mucosal strips was explored as well as downstream kinases modulating SGLT-1 and GLUT2 glucose transporters.
Oral glucose tolerance test carried out in rodents showed that oral administration of RELM-β increased glycemia. Studies in rat jejunal tissue indicated that mucosal RELM-β promoted absorption of glucose from the gut lumen. RELM-β had no effect on paracellular mannitol transport, suggesting a transporter-mediated transcellular mechanism. In studies with jejunal mucosa mounted in Ussing chamber, luminal RELM-β inhibited SGLT-1 activity in line with a diminished SGLT-1 abundance in brush border membranes (BBMs). Further, the potentiating effect of RELM-β on jejunal glucose uptake was associated with an increased abundance of GLUT2 at BBMs. The effects of RELM-β were associated with an increased amount of protein kinase C βII in BBMs and an increased phosphorylation of AMP-activated protein kinase (AMPK).
The regulation of SGLT-1 and GLUT2 by RELM-β expands the role of gut hormones in short-term AMPK/protein kinase C mediated control of energy balance.
PMCID: PMC2731541  PMID: 19502416
15.  Massive gastrointestinal bleeding due to isolated jejunal varices in a patient without portal hypertension 
Isolated ectopic varices located in the small bowel are uncommon. Portal hypertension caused by liver cirrhosis is the most common predisposing risk factor.
We present an unusual case of massive gastrointestinal bleeding from idiopathic jejunal varices in a 73-year-old Caucasian male without portal hypertension. Exploratory laparotomy disclosed ectopic varices located in the small intestine. Segmental resection of the jejunum with end to end anastomosis resulted in a complete resolution of the haemorrhage. During a 5 year follow up, the patient is stable with no bleeding recurrence.
Information on aetiology, diagnosis and management of jejunal varices is reviewed.
Diagnosis and management of isolated jejunal varices is challenging. Surgeons as well as acute care physicians have to consider idiopatic form of jejunal varices as a potential cause of gastrointestinal bleeding when gastroduodenoscopy and colonoscopy are negative.
PMCID: PMC3731695  PMID: 23528981
Jejunal varices; Gastrointestinal haemorrhage; Diagnosis; Management
16.  Development of a novel approach to safely couple the intestine to a distraction-induced device for intestinal growth: Use of reconstructive tissue matrix 
Pediatric surgery international  2013;29(2):151-156.
Distraction-induced intestinal growth may be a novel treatment for short bowel syndrome. Longitudinal, distractive tension created by the application of force creates a significant challenge: to produce adequate force, yet not cause perforation at the fixation points. This paper describes our development of a coupling strategy to allow for successful bowel lengthening.
A curvilinear hydraulic device was implanted in an isolated Roux limb of small bowel in young Yorkshire pigs. Bowel was lengthened over a 2 week period. Study groups included: Group 1: Twelve silk transmural anchoring sutures into an engineered-coupling ring at each device end. Group 2: Addition of felt pledgets to the coupling rings on the serosal surface of the small bowel. Group 3: Extraluminal use of either thin AlloDerm®, thick AlloDerm®, or Strattice™ mesh to anchor the device.
Group 1 (suture-only) resulted in a gradual pulling through of the suture with increasing tension and no lengthening. Felt pledgets eroded in a similar fashion, causing abdominal sepsis. Thin AlloDerm® failed to prevent erosion, however it protected against gross contamination. Animals in which either thick AlloDerm® or Strattice™ mesh was used survived complication-free to the study endpoint. Both thick AlloDerm® and Strattice™ prevented erosion and perforation allowing for an average of 10.85-cm expansion.
This study demonstrates use of either thick AlloDerm® or Strattice™ reconstructive tissue matrix allows for safe and effective coupling. Further, we suggest this approach could be an adjunct to esophageal lengthening procedures.
PMCID: PMC3557585  PMID: 23108982
short bowel syndrome; mechanotransduction; intestine; distraction-induced growth; reconstructive tissue matrix
17.  Evidence for peptidoglycan absorption in rats with experimental small bowel bacterial overgrowth. 
Infection and Immunity  1991;59(2):555-562.
Surgical creation of jejunal self-filling blind loops (SFBL) causes small bowel bacterial overgrowth which is associated with hepatobiliary inflammation in the susceptible Lewis and Wistar rat strains. Since hepatic injury occurs when small bowel anaerobic bacterial concentrations are increased 4 to 6 log10 units per ml and hepatic bacterial cultures are negative, we postulate that the inflammation is caused by absorption of phlogistic cell wall polymers originating from bacteria within the loop. To demonstrate absorption of bacterial cell wall polymers, we measured plasma and hepatic levels of immunoreactive peptidoglycan-polysaccharide (PG-PS) following intraluminal injection as well as anti-PG antibodies as an indirect measure of absorption and/or accumulation of endogenous PG. PG-PS purified from group A streptococci was detected in plasma by enzyme-linked immunosorbent assay after intraluminal injection; rats with SFBL showed significantly more uptake into plasma and the liver than sham-operated rats or SFBL rats which were treated with metronidazole (P less than 0.025). Total plasma immunoglobulin A (IgA), IgG, and IgM levels did not differ among sham-operated rats and those with self-emptying blind loops or SFBL, but plasma anti-PG IgA (P less than 0.05), IgG, and IgM (P less than 0.01) levels were increased in rats with SFBL. Metronidazole and tetracycline prevented the elevation of anti-PG antibody, but gentamicin and polymyxin B did not. Anti-lipid A, anti-soy protein, and anti-chow antibodies in plasma were not consistently increased in rats with SFBL indicating the lack of a generalized antibody response to luminal antigens. These data suggest that PG from normal flora bacteria is absorbed from the intestinal lumen and that mucosal injury and/or increased luminal concentrations of PG, such as those induced by small bowel bacterial overgrowth, lead to enhanced absorption of potentially inflammatory bacterial polymers.
PMCID: PMC257785  PMID: 1987073
18.  Nyctohemeral growth hormone levels in children with growth retardation and inflammatory bowel disease , 12 
Gut  1973;14(3):191-195.
Short stature is a common complication of inflammatory bowel disease. Recently McCaffery, Nasr, Lawrence, and Kirsner (1970) concluded, from blood growth hormone (GH) levels obtained during insulin-hypoglycaemic provocation, that GH deficiency contributed to the retardation in growth observed in subjects with inflammatory bowel disease. Although it was not possible to eliminate the possibility of partial hypopituitarism, this study does not confirm the existence of GH deficiency in six subjects with short stature complicating inflammatory bowel disease. The nyctohemeral (night and day) serum GH is described, and the insulin and glucose levels in these subjects and normal sleep-related GH rises in all are demonstrated. This finding is not compatible with growth hormone deficiency. In one subject the response to arginine provocation was blunted. Three subjects manifested hyperinsulinism and evidence for `insulin resistance'. These findings are unexplained but suggest that insulin resistance may contribute to a blunted GH response to insulin-induced hypoglycaemia. Blunted GH response to both arginine and insulin-induced hypoglycaemia may also result from continuous secretion and reduced pituitary storage of growth hormone. This possibility is suggested by the pattern of raised blood GH levels in one of the subjects.
PMCID: PMC1412609  PMID: 4735568
19.  Salmonella enterica serovar Choleraesuis infection of the porcine jejunal Peyer’s patch rapidly induces IL-1β and IL-8 expression 
Salmonella enterica serovar Choleraesuis is an enteric pathogen of swine, producing septicemia, enterocolitis, pneumonia, and hepatitis. The initial molecular events at the site of Salmonella infection are hypothesized to be critical in the initiation of innate and adaptive immune responses; however the acute immune response elicited by porcine intestinal tissues is not well understood. To address this need, we employed explants of jejunal Peyer’s patch (JPP) mucosa from pigs to examine Salmonella-induced immune responses under controlled conditions as well as to overcome limitations of whole animal approaches. JPP explants mounted in Ussing chambers maintained normal histological structure for 2 h and stable short-circuit current and electrical conductance for 2.5 h. After ex vivo luminal exposure to Salmonella serovar Choleraesuis, JPP responded with an increase in mRNA expression of IL-1β and IL-8, but not TNFα. Increased IL-1β and IL-8 expression were dependent on efficient Salmonella adhesion and internalization, whereas mutant Salmonella did not induce inflammatory cytokine expression. Commensal enteric bacteria, present in some experiments, also did not induce inflammatory cytokine expression. These findings indicate that Salmonella uptake by Peyer’s patch is important in the induction of an innate response involving expression of IL-1β and IL-8, and that ex vivo intestinal immune tissue explants provide an intact tissue model that will facilitate investigation of mucosal immunity in swine.
PMCID: PMC2613298  PMID: 16115691
animal models; swine; cytokines; interleukins; mucosal immunology
20.  Phytobezoar in Meckel's diverticulum: A rare cause of small bowel obstruction 
Meckel's diverticulum (MD) is the prevailing anomaly of the gastrointestinal tract, found in about 2% of the population; it rarely gives rise to symptoms and its discovery is usually accidental. Phytobezoar is a concretion of poorly digested fruit and vegetable fibres that is found in the alimentary tract and rarely can be the cause of small intestinal obstruction. Herein we report a rare case of intestinal obstruction due to phytobezoar formation into a MD.
Presentation of case
A 50 year-old patient, was admitted to author's institution with an history of abdominal pain, nausea and multiples episodes of vomiting. Plain X-ray showed dilated small-bowel loops. Computed tomography (CT) revealed jejunal loops with air-fluid levels. The patient underwent explorative laparotomy where we found a giant Meckel's diverticulum, filled by a phytobezoar that caused small bowel compression. We performed a segmental ileal, resection, containing the MD. The histological exam confirmed Meckel's diverticulum.
Bowel obstruction due to a phytobezoar in a Meckel's diverticulum is rare: only 7 cases have been reported in literature. MD complications are rare and phytobezoar is one of them with only few cases described in literature.
The conventional x rays studies were inconclusive whereas abdominal contrast enhanced CT led to a definitive diagnosis. Explorative laparotomy or laparoscopy is mandatory in these cases.
PMCID: PMC3316763  PMID: 22382033
Meckel's diverticulum; Phytobezoar; Small bowel obstruction; Acute abdomen
21.  Jejunal Diverticular Perforation due to Enterolith 
Case Reports in Gastroenterology  2011;5(2):445-451.
Jejunal diverticulosis is a rare entity with variable clinical and anatomical presentations. Although there is no consensus on the management of asymptomatic jejunal diverticular disease, some complications are potentially life-threatening and require early surgical treatment. Small bowel perforation secondary to jejunal diverticulitis by enteroliths is rare. The aim of this study was to report a case of small intestinal perforation caused by a large jejunal enterolith. An 86-year-old woman was admitted with signs of diffuse peritonitis. After initial fluid recovery the patient underwent emergency laparotomy. The surgery showed that she had small bowel diverticular disease, mainly localized in the proximal jejunum. The peritonitis was due to intestinal perforation caused by an enterolith 12 cm in length, localized inside one of these diverticula. The intestinal segment containing the perforated diverticulum with the enterolith was removed and an end-to-end anastomosis was done to reconstruct the intestinal transit. The patient recovered well and was discharged from hospital on the 5th postoperative day. There were no signs of abdominal pain 1 year after the surgical procedure. Although jejunal diverticular disease with its complications, such as formation of enteroliths, is difficult to suspect in patients with peritonitis, it should be considered as a possible source of abdominal infection in the elderly patient when more common diagnoses have been excluded.
PMCID: PMC3180661  PMID: 21960947
Diverticulum; Intestines; Lithiasis; Intestinal perforation; Diverticulitis
22.  Meal-stimulated release of methionine-enkephalin into the canine jejunal lumen. 
Journal of Clinical Investigation  1988;81(3):822-825.
Application of enkephalins to the luminal surface of the bowel augments intestinal absorption. However, to date, endogenous enkephalins have not been demonstrated within intestinal luminal fluid. To determine whether enkephalins are present in the intestinal lumen, five adult dogs had 25-cm chronic jejunal Thiry-Vella loops constructed. Dogs were studied in the awake, fasted state. Jejunal loops were perfused with isoosmotic, neutral Krebs buffer containing protease inhibitors. After basal sampling, the dogs received a high fat meat meal. Collections were made during the meal and for 60 min postprandially. Luminal met-enkephalin levels were determined by radioimmunoassay and confirmed by HPLC. HPLC separation of luminal samples demonstrated two immunoreactive peaks which co-eluted with pure met-enkephalin and met-enkephalin-sulfoxide. Basal met-enkephalin outputs averaged 52 +/- 13 ng/min. The meal significantly increased mean luminal met-enkephalin output to 137 +/- 71 ng/min. During the initial 20-min postprandial period, output remained elevated (180 +/- 73 ng/min), after which it returned to basal levels. We conclude that met-enkephalin is present in the jejunal lumen, and that luminal release of this opioid is augmented by a meal.
PMCID: PMC442532  PMID: 3343342
23.  Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors 
Purpose of review
To summarize recent evidence that IGF1 mediates growth effects of multiple trophic factors and discuss clinical relevance.
Recent findings
Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogues in short bowel syndrome and Crohn’s disease. This review highlights evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn’s disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that SOCS protein induction by GH or GLP2 in normal or inflamed intestine, may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed.
IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.
PMCID: PMC3685151  PMID: 22241077
intestinal growth; enterotrophic therapy; short bowel syndrome; Crohn’s disease
24.  Enteroglucagon and experimental intestinal carcinogenesis in the rat. 
Gut  1987;28(1):33-39.
To assess the association between the putative intestinal trophic hormone enteroglucagon and the development of intestinal tumours, four groups of 20 rats underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg weekly for 12 weeks. At 26 weeks there was a promotion of colonic neoplasia from a median of 0.5 (range 0-3) per rat in the transection group to 1.0 (0-3) in the 50% resected group (p less than 0.01) but no significant promotion in the 80% resection group. In the small bowel, increasing resection resulted in a progressive promotion of tumours from a median of 1.0 (range 0-3) per rat in the transection group to 2.0 (0-5) in the 50% resection group (p less than 0.001) and 3.0 (0-11) in the 80% group (p less than 0.01). Plasma enteroglucagon was measured at 2, 16, and 26 weeks and was raised seven-fold in the 80% resected group (p less than 0.001). There was a significant correlation between enteroglucagon concentrations and number of duodenal tumours but not colonic tumours. Crypt cell production rate in the duodenum increased from 11.5 +/- 1.9 to 29.2 +/- 1.4 cells/crypt/h in the 80% resected group (p less than 0.001) and showed a close correlation with both enteroglucagon levels and tumour promotion in the small bowel. There were no changes in crypt cell production rate in the colon with resection. This study shows a close association between enteroglucagon concentrations, promotion of tumours and crypt cell production rate in the duodenum but not in the colon.
PMCID: PMC1432717  PMID: 3817582
25.  Induction and maintenance of mucosal enterokinase activity in proximal small intestine by a genetically determined response to mediated sodium transport 
Gut  1981;22(10):804-811.
Mucosal enterokinase activity was established at intervals throughout the small intestine in guinea-pigs; maximum activity was present in the duodenum and proximal jejunum in new born as well as adult animals. Transposition of 5 cm lengths of small gut from the high enterokinase containing proximal region to the distal intestine and vice versa showed that mucosal enterokinase activity in the transposed segments was little changed after several weeks of healthy life. Isolation of proximal jejunal loops from luminal continuity resulted in the fall of mucosal enterokinase activity to minimal levels within 16 hours. Low levels of mucosal enterokinase activity were identified in loops of both proximal and distal jejunum 12 weeks after isolation. Luminal perfusion studies in vivo in proximal jejunal loops 24 hours after isolation showed that mucosal enterokinase activity could be restored to near normal levels within four to six hours by luminal sodium in the presence of active pancreatic endopeptidases, oligopeptides, L-amino acids, or D-glucose but not D-amino acids or D-fructose. Near normal mucosal enterokinase activity persisted in the loops for as long as luminal perfusion with 144 mM sodium and L-lysine or trypsin was maintained (24 hours). The time course of the restoration of mucosal enterokinase activity was compatible with an initial precursor activation as well as biosynthesis. The requirement for luminal sodium appeared to be absolute regardless of the co-substrate and supports the conclusion that mucosal enterokinase activity is dependent on mediated sodium transport. The ability of proximal intestinal enterocytes to respond to sodium flux with an increase in enterokinase activity is a property determined in intrauterine life: distal intestinal enterocytes may have functioning structural genes for enterokinase but appear to be unable to respond.
PMCID: PMC1419421  PMID: 7028575

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