Intestinal Structural Changes Research Articles

Effect of elevated intra-abdominal pressure and 100% oxygen on superior mesenteric artery blood flow and enterocyte turnover in a rat

Elevated intra-abdominal pressure (IAP) has been shown to reduce mesenteric blood flow and cause intestinal damage. The purpose of the present study was to evaluate the effects of IAP and hyperoxia on superior mesenteric artery (SMA) blood flow, enterocyte proliferation and apoptosis in a rat model of abdominal compartment syndrome (ACS). Male rats underwent midline laparotomy. SMA was isolated and ultrasonic blood flow probes were placed on the vessel for continuous measurement of regional blood flow. Two catheters were introduced into the peritoneal cavity for inflation of air and for measurement of IAP. Rats were divided into three experimental groups: (1) Sham rats were subjected to IAP of 0 mmHg, (2) ACS-air rats were subjected to IAP of 6 mmHg for 2 h and were ventilated with air, and (3) ACS-O(2) rats were subjected to IAP of 6 mmHg and were ventilated with 100% oxygen (O(2)) during the operation and for 6 h after the operation. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were evaluated at 24 h after operation. A paired Student's t test and the non-parametric Kruskal-Wallis ANOVA test were used as indicated. P < 0.05 was considered statistically significant. IAP at 6 mmHg caused a moderate decrease in SMA blood flow. Inhalation of 100% oxygen resulted in a trend toward an increase in SMA flow when compared to air-ventilated animals. ACS rats demonstrated a significantly lower index of proliferation in jejunum and ileum as well as a significantly greater apoptotic index in jejunum compared to sham animals. Exposure to 100% oxygen resulted in a significant increase in cell proliferation in jejunum and ileum as well as in a significant decrease in cell apoptosis in jejunum compared to air-breathing animals. In a rat model of ACS, elevated IAP decreases SMA blood flow and inhibits enterocyte turnover. Hyperoxia results in a trend toward an increase in SMA blood flow, increases enterocyte proliferation and inhibits cell death via apoptosis. These findings may have significant implications for ventilation strategies during laparoscopy.

Substance P Receptor Antagonism for Treatment of Cryptosporidiosis in Immunosuppressed Mice

Cryptosporidiosis, caused by the protozoan parasite Cryptosporidium parvum, causes self-limited diarrhea in normal hosts but can cause life-threatening diarrhea for immunosuppressed patients. There is an urgent need for new drugs to treat this chronic disease. Cryptosporidium parvum infection is associated with intestinal structural and pathophysiologic changes, including villi blunting and glucose malabsorption. Substance P (SP), a neuropeptide and pain transmitter, is associated with the gastrointestinal tract and is elevated in humans and macaques after experimental C. parvum challenge. To examine the relevance of SP in the pathogenesis of cryptosporidiosis, and to determine if SP receptor antagonism can be employed for treatment of cryptosporidiosis in immunosuppressed hosts, we used an immunosuppressed murine model (dexamethasone-immunosuppressed mice) that is frequently utilized for examining chemotherapeutic potential of drugs. Quantitative ELISA was used to measure intestinal SP levels in immunosuppressed mice with, and without, C. parvum infection. Intestinal physiological alterations, as studied by the Ussing chamber technique, plus weight change, fecal oocyst shedding, and villi measurements, were compared in infected mice with, and without, SP receptor antagonist (aprepitant) treatment. Immunosuppressed mice infected with C. parvum demonstrated increased SP levels as well as physiological alterations (glucose malabsorption), weight loss, fecal oocyst shedding, and structural alterations (increased intestinal villi blunting) compared to uninfected mice. Each of these defects was significantly inhibited by aprepitant treatment. These studies demonstrate the potential of SP receptor antagonism for treatment of pathogenesis of cryptosporidiosis in immunosuppressed hosts.

Effect of 100% oxygen on E-selectin expression, recruitment of neutrophils and enterocyte apoptosis following intestinal ischemia-reperfusion in a rat

Recent evidence suggests that neutrophil recruitment may initiate cell apoptosis in ischemic tissues. We have recently shown that enterocyte apoptosis is increased following intestinal ischemia-reperfusion (IR) injury. The purpose of the present study was to examine the effect of hyperoxia on E-selectin expression, neutrophil recruitment and enterocyte apoptosis following intestinal IR in a rat. Male Sprague-Dawley rats were divided into three experimental groups: (1) sham rats underwent laparotomy without vascular occlusion and were ventilated with air (Sham) (2) IR rats underwent occlusion of both the superior mesenteric artery and portal vein for 30 min and were ventilated with air (IR), and (3) IR-O2 rats underwent IR and were ventilated with 100% started 10 min before reperfusion and continued for 6 h (IR-O2). Intestinal structural changes were determined 24 h following IR. Immunohistochemistry for E-selectin (using E-selectin cleaved concentrated polyclonal antibody) was performed to identify E-selectin immunoreactivity localized to the endothelium of venules. The recruitment of neutrophils was calculated per 100 venules. Immunohistochemistry for Caspase-3 was performed for identification of apoptotic cells. Non-parametric one-way ANOVA test was used for statistical analysis with p less than 0.05 considered statistically significant. A significant increase in E-selectin expression in the jejunum (6.1 +/- 2.2 vs. 2.5 +/- 1.0 E-selectin positive vessels/100 vessels, p < 0.05) and ileum (12.1 +/- 2.7 vs. 3.3 +/- 1.2 E-selectin positive vessels/100 vessels, p < 0.05) and a concomitant increase in neutrophil recruitment in the ileum (5.5 +/- 1.6 vs. 1.3 +/- 0.6 adhered PMN's per 100 venules) were observed in IR rats compared to sham animals and were accompanied by increased cell apoptosis (p < 0.05). Treatment with 100% oxygen resulted in a significant attenuation in E-selectin expression in the ileum (2.7 +/- 1.1 vs. 12.1 +/- 2.7 E-selectin positive vessels/100 vessels, p < 0.05), and neutrophil recruitment in the jejunum (2.5 +/- 1.4 vs. 7.7 +/- 1.9 adhered PMN's per 100 venules, p < 0.05) and ileum (1.5 +/- 0.7 vs. 5.5 +/- 1.6 adhered PMN's per 100 venules, p < 0.05) compared to IR animals, and was accompanied by decreased cell apoptosis (p < 0.05). Hyperoxia inhibits enterocyte apoptosis following intestinal ischemia-reperfusion. Down-regulation of E-selectin expression with subsequent decrease in neutrophil recruitment may be responsible for this effect.

Oral insulin up-regulates Toll-like receptor 4 expression and enhances intestinal recovery following lipopolysaccharide-induced gut injury in a rat.

In the present study, we evaluated the protective effect of oral insulin (OI) on intestinal mucosa following lipopolysaccharide-induced intestinal damage in a rat. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats, LPS-rats that were treated with lipopolysaccharide (LPS), and LPS-INS rats that were treated with OI given in drinking water 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, enterocyte apoptosis, and mucosal expression of Toll-like receptor 4 (TLR4) were determined 24 h after the last LPS injection. LPS-INS animals showed a significantly greater bowel and mucosal weight in jejunum and ileum, mucosal DNA and protein in jejunum and ileum, villus height in ileum, crypt depth in jejunum and ileum, cell proliferation rates in jejunum, and significantly lower apoptotic index in ileum compared to LPS- animals. LPS rats demonstrated 50% increase in TLR4 expression in jejunum compared to sham animals. Treatment with OI resulted in a three-fold increase in TLR4 expression in jejunum, compared to LPS animals. In conclusion, OI improves intestinal recovery after LPS endotoxemia in a rat.

Effect of probiotics on intestinal regrowth and bacterial translocation after massive small bowel resection in a rat

Background/Purpose Because of their ability to inhibit intestinal bacterial overgrowth, probiotics (PROs) have been advocated for the treatment of patients with short bowel syndrome (SBS). This study was conducted to determine the effect of PROs on bacterial translocation and intestinal regrowth after massive small bowel resection in a rat. Methods Male Sprague-Dawley rats were divided into 3 experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent 75% small bowel resection, and SBS-PRO rats underwent bowel resection and were treated with a PRO given in drinking water from day 4 through 14. Intestinal structural changes (bowel circumference, overall bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, enterocyte proliferation and enterocyte apoptosis) and bacterial translocation (BT) to mesenteric lymph nodes, liver, portal blood, and peripheral blood were determined on day 15 after operation. Results Sham rats exhibited a 20% BT to the mesenteric lymph nodes (level I), liver (level II), and blood (level III). Short bowel syndrome rats demonstrated a 100% BT to lymph nodes (level I) and liver (level II) and 40% translocation to peripheral blood (level III). Treatment with PROs resulted in a significant decrease in BT to all 3 target organs and decreased enterocyte apoptosis compared with SBS-untreated animals. Short bowel syndrome rats showed a significant increase (vs sham) in jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth. Short bowel syndrome rats also had a greater proliferation index and apoptotic index in both jejunum and ileum compared with sham animals. SBS-PRO rats showed a significant increase (vs SBS rats) in crypt depth in ileum and a mild decrease in apoptotic index in jejunum and ileum, compared with SBS-untreated animals. Conclusions In a rat model of SBS, PROs decrease BT through mechanisms which maybe dependent on intestinal mucosal integrity.

Oral Glutamine Prevents Gut Mucosal Injury and Improves Mucosal Recovery Following Lipopolysaccharide Endotoxemia in a Rat

To evaluate the effects of oral glutamine in preventing mucosal damage caused by lipopolysaccharide (LPS) endotoxemia in a rat. Male Sprague Dawley rats, weighing 250 to 280 g, were divided into three experimental groups: CONTR rats (Group A), LPS rats (Group B) were treated with lipopolysaccharide given I.P. at dose 10 mg/kg every 24 h (two injections), and LPS-GLN rats (Group C) were treated with oral glutamine given in drinking water (2%) 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h after last LPS injection. LPS rats demonstrated a significant decrease in bowel and mucosal weight in jejunum and ileum, mucosal DNA and protein in jejunum and ileum, and villus height and crypt depth in jejunum and ileum compared with sham animals. LPS rats also had a significantly greater Park injury score in jejunum and ileum, a lower cell proliferation index in jejunum and ileum, and higher apoptotic index in jejunum and ileum compared with control rats. LPS-GLN animals showed a significant increase in bowel weight in jejunum, mucosal weight in jejunum and ileum, mucosal DNA in jejunum and ileum, villus height in jejunum and ileum, and cell proliferation index compared with LPS animals. The Park injury score was significantly lower in LPS-GLN rats compared with LPS animals. Oral glutamine supplementation prevents mucosal injury and improves intestinal recovery after LPS endotoxemia in a rat.

The effect of leptin on intestinal recovery following ischemia-reperfusion injury in a rat

Recent evidence suggests that the adipose tissue derived cytokine leptin (LEP) is involved in the modulation of growth and differentiation of normal small intestine. The purpose of the present study was to examine the effect of leptin on enterocyte turnover and intestinal recovery after ischemia-reperfusion (IR) injury in a rat. Male Sprague-Dawley rats were divided into three experimental groups: (1) sham rats underwent laparotomy, (2) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 24 h of reperfusion, and (3) IR-LEP rats underwent IR and were treated with leptin given subcutaneously at a dose of 50 microg/kg once a day for 48 h before and 24 h following IR. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with P < 0.05 considered statistically significant. Treatment with leptin resulted in a significant increase in bowel weight in ileum, mucosal weight in jejunum and ileum, mucosal DNA content in ileum, mucosal protein content in jejunum and ileum, villus height in jejunum and ileum, and crypt depth in jejunum compared to IR-animals. IR-LEP rats also had a significantly lower intestinal injury score as well as lower apoptotic index and higher cell proliferation index in jejunum and ileum compared to the IR-animals. In conclusion, pre-treatment with leptin prevents gut mucosal damage and improves intestinal rehabilitation following intestinal IR in a rat.

Adverse Effects of Increased Intra-abdominal Pressure on Small Bowel Structure and Bacterial Translocation in the Rat

The purpose of this study was to evaluate the effects of elevated intra-abdominal pressure (IAP) on intestinal structures and bacterial translocation in the rat. Forty-two male Sprague-Dawley rats were randomly divided into three experimental groups of 14 rats each: the sham group underwent insertion of a balloon-tipped catheter; the IAP-15 group was subjected to a 15 mm Hg pneumoperitoneum for 60 minutes; and the IAP-25 group was subjected to a 25 mm Hg pneumoperitoneum for 60 minutes. Intestinal structural changes (bowel circumference, overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth) and bacterial translocation to mesenteric lymph nodes, liver, spleen, portal blood, and peripheral blood were determined 24 hours following pneumoperitoneum. IAP-15 and IAP-25 rats demonstrated a significant decrease in: bowel and mucosal weight in the duodenum, jejunum, and ileum; mucosal DNA and protein in the jejunum and ileum; villus height in the jejunum: and crypt depth in the jejunum and ileum compared to the sham rats. Bacterial translocation was demonstrated in 60% of IAP-15 rats and in 80% of IAP-25 rats. Elevated IAP results in mucosal injury of the gut, causing mucosal hypoplasia, and increases bacterial translocation.

SIMVASTATIN ATTENUATES POSTBURN INTESTINAL TISSUE DAMAGE IN RATS.

Objective: To test the effects of early postburn treatment with statins on major postburn sepsis pathogenesis in the form of gut inflammation and transepithelial leakiness. Rationale: We and others have demonstrated intestinal structural and permeability changes within three days after major thermal injury (Critical Care Medicine 32:1730-9, 2004). These changes are associated with gut tissue inflammation and immediate postburn systemic neutrophil hyperactivation and extravasation. Here, we hypothesize that such changes can be suppressed by treatment with simvastatin which had been shown to have antiinflammatory effects that include inhibition of neutrophil extravasation (Circulation 106:2104-2110, 2002). Methods: Utilizing a rat burn model with third degree burn over 30% total body surface area, we assessed gut inflammation and transepithelial permeability three days postburn with or without daily intraperitoneal injection of simvastatin. Gut inflammation was assessed by measuring tissue myeloperoxidase (MPO) activity and nitrotyrosine immunohistochemistry. Transepithelial leakiness across ex vivo gut specimens was measured utilizing FITC-dextran-40S with an Ussing diffusion chamber. Results: Our results show a substantial increase in tissue MPO activity and nitrotyrosine immunoreactivity in rat ileum and mesenteric lymph nodes 1 to 3 days postburn. However, both MPO activity and nitrotyrosine immunolabeling were largely diminished in sham and simvastatin-treated rats. Furthermore, transepithelial large molecule leakage was increased three days postburn with evidence of paracellular transport. This leakage was also significantly attenuated in sham rats and in simvastatintreated postburn rats. Conclusion: Simvastatin treatment appears to be beneficial in preventing inflammation-mediated postburn gut tissue damage that is presumed to precipitate postburn sepsis pathogenesis. Acknowledgements: This work was supported by National NIH grant# 3 S06 GM008043-34S1 (project# 6) and by NSF BIOMRI Award# DBI-0520869.

Beneficial Effects of Oral Insulin on Intestinal Recovery Following Ischemia-Reperfusion Injury in Rat 1

It has been reported that oral insulin has a trophic effect on intestinal mucosa, but the precise mechanism of its action is still unclear. The purpose of the present study was to investigate the effect of oral insulin on ischemia-reperfusion (IR) intestinal mucosal injury in rat. Male Sprague-Dawley rats underwent laparotomy (Sham) or IR-intestinal damage by clamping both the superior mesenteric artery and the portal vein for 30 min followed by 24 h reperfusion. IR-INS rats were treated with oral insulin given in drinking water (1U/ml) 48 h before and after IR. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h after IR. Park's score was used for the quantitative assessment of histological change. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with P less than 0.05 considered statistically significant. IR-injury resulted in a significant decrease in bowel weight in jejunum, mucosal weight in jejunum and ileum, villus height in jejunum and ileum, cell proliferation index in jejunum, and ileum compared to sham animals. IR-INS animals demonstrated greater duodenal and jejunal bowel weight, duodenal, jejunal and ileal mucosal weight, jejunal mucosal DNA, jejunal and ileal mucosal protein, jejunal and ileal villus height and crypt depth, jejunal and ileal proliferation index compared to IR-animals. Oral insulin administration induced also a significant decrease in apoptotic index in ileum (1.2 +/- 0.4 versus 2.8 +/- 0.7 TUNEL positive cells/10 villi, P < 0.05) compared to IR-untreated animals. Oral insulin improves intestinal recovery after IR- injury in rat.

Transient changes of transforming growth factor-β expression in the small intestine of the pig in association with weaning

It is well known that early weaning causes marked changes in intestinal structure and function, and transforming growth factor-beta (TGF-beta) is believed to play an important regulatory role in post-weaning adaptation of the small intestine. The present study examined the distribution and expression intensity of TGF-beta in the small intestinal mucosa of pre- and post-weaning pigs using a specific immunostaining technique and Western blot analysis. The level of TGF-beta in the intestinal mucosa, as estimated by Western blot analysis, did not change significantly during weaning. However, when examined by the immunostaining technique, TGF-beta1 (one of the TGF-beta isoforms dominantly expressed in the tissue) at the intestinal villus epithelium, particularly at the apical membrane of the epithelium, decreased significantly 4 d after weaning, while the staining intensity increased significantly at the intestinal crypts compared with that in pre-weaning pigs. These changes were transient, with the immunostaining intensity for TGF-beta1 at the intestinal villi and the crypts returning to the pre-weaning level by 8 d post-weaning. The transient decrease in TGF-beta1 level at the intestinal villus epithelium was associated with obvious intestinal villus atrophy and marked reduction of mucosal digestive enzyme activities. Furthermore, the number of leucocytes staining positively for TGF-beta1 increased significantly in the pig intestinal lamina propria 4 d after weaning. These findings strongly suggest that TGF-beta plays an important role in the post-weaning adaptation process in the intestine of the pig.

Oral arginine improves intestinal recovery following ischemia-reperfusion injury in rat

Arginine and nitric oxide are critical to the normal physiology of the gastrointestinal tract and maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluate the effects of oral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis following intestinal ischemia-reperfusion (IR) in the rat. Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent laparotomy and superior mesenteric artery mobilization, IR rats underwent superior mesenteric artery occlusion for 30 min following by 24 h of reperfusion, and IR-ARG rats were treated with enteral arginine given in drinking water (2%) 48 h before and following IR. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with p <0.05 considered statistically significant. IR rats demonstrated a significant decrease in bowel weight in duodenum and jejunum, mucosal weight in jejunum and ileum, and villus height in jejunum and ileum compared with control animals. IR rats also had a significantly lower cell proliferation index in jejunum and ileum and a higher apoptotic index in ileum compared with control rats. IR-ARG animals demonstrated greater duodenal and jejunal bowel weight; duodenal, jejunal, and ileal mucosal weight; and jejunal and ileal cell proliferation index compared with IR animals. In conclusion, oral ARG administration improves mucosal recovery following IR injury in the rat.

Oral arginine reduces gut mucosal injury caused by lipopolysaccharide endotoxemia in rat

The objective of this study was to evaluate the effects of lipopolysaccharide (LPS) endotoxemia and enteral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis in rat. Male Sprague-Dawley rats, weighing 250-280 g, were divided into three experimental groups: control rats, LPS rats treated with lipopolysaccharide given ip at a dose of 10 mg/kg every 24 h (two injections), and LPS-ARG rats treated with enteral arginine given in drinking water (2%) 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined on day 3 following the first LPS injection. LPS rats demonstrated a significant decrease in bowel weight in duodenum, mucosal weight in duodenum, jejunum, and ileum, mucosal DNA and protein in jejunum and ileum, and villus height in jejunum and ileum compared to control animals. LPS rats also had a significantly lower cell proliferation index in jejunum and ileum and a higher apoptotic index in jejunum and ileum compared to control rats. LPS-ARG animals demonstrated greater duodenal bowel weight, duodenal and ileal mucosal weight, ileal mucosal DNA and protein, ileal villus height, and jejunal and ileal cell proliferation index compared to LPS animals. LPS endotoxemia impairs the integrity of the gastrointestinal mucosa in rat. Decreased cell proliferation and increased apoptosis may be considered the main mechanisms responsible for the decreased cell mass. Enteral arginine administration decreases the mucosal injury caused by lipopolysaccharide.

Route of nutrient delivery

Nutritional intervention early in the course of critical illness in humans and animals can have a significant impact on morbidity and mortality. Enteral delivery of nutrients is less technically demanding, more physiologic, and less expensive than parenteral nutrition. Furthermore, as complete bowel rest during critical illness can be associated with detrimental intestinal structural and functional changes ultimately resulting in bacterial translocation from the gut, direct delivery of nutrients to the gastrointestinal tract is preferred in patients with sufficient gastrointestinal function to allow digestion and absorption of nutrients. Once the decision to “feed the gut” has been established, there are several routes of enteral nutrient delivery available. A sound knowledge of gastrointestinal function, anticipated duration of enteral support, and co-moribund conditions will help the clinician tailor a plan of nutrient delivery that optimally meets each patient’s needs. This article will review available routes of nutrient delivery to the gastrointestinal tract, and discuss indications and contraindications for each.

Structural and functional alterations of the gastrointestinal tract following radiation-induced injury in the rhesus monkey.

A severe and debilitating diarrhea is a dose-limiting toxic result for patients receiving abdominal radiation or chemotherapy. To correlate changes in intestinal structure and function, nonhuman primates were exposed to 9.5 Gy total abdominal x-irradiation. Diarrhea and weight loss were correlated with intestinal crypt and villus histology, in vivo assessed intestinal permeability, and ex vivo functional studies performed in Ussing chamber assays before and at 7, 14, and 35 days after irradiation. Peak gut structural damage occurred early and paralleled functional changes of the intestinal mucosa, including increased epithelial permeability (both in vivo and ex vivo), activation of secretory pathways, decreased nutrient absorption, diarrhea, and weight loss. Recovery of gut integrity and epithelial resistance began thereafter, in spite of incomplete histological recovery. Our integrated approach allowed a comprehensive study of the relationship between postirradiation tissue injury and changes in function over time in the gastrointestinal tract of the nonhuman primate.

Epidermal growth factor is critical for intestinal adaptation following small bowel resection

The loss of small intestinal mucosal surface area is a relatively common clinical situation seen in both the pediatric and adult population. The most frequent causes include mesenteric ischemia, trauma, inflammatory bowel disease, necrotizing enterocolitis, and volvulus. Following surgical resection, the remnant intestine compensates or adapts to the loss of native bowel by increasing its absorptive surface area and functional capacity. Unfortunately, many patients fail to adapt adequately, and are relegated to lifelong intravenous nutrition. Research into intestinal adaptation following small bowel resection (SBR) has evolved only recently from the gross and microscopic level to the biochemical and genetic level. As understanding of this process has increased, numerous therapeutic strategies to augment adaptation have been proposed. Epidermal growth factor (EGF) is an endogenous peptide that is secreted into the gastrointestinal tract and able to influence gut ontogeny, as well as mucosal healing. Early studies have demonstrated its ability to augment the adaptive process. Focusing on a murine model of massive intestinal loss, the morphological, structural, biochemical, and genetic changes that occur during the intestinal adaptive process will be reviewed. The role of EGF and its receptor as critical mediators of the adaptive process will be discussed. Additionally, the ability of EGF to augment intestinal proliferation and diminish programmed cell death (apoptosis) following SBR will be examined. Enhancing adaptation in a controlled manner may allow patients to transition off parenteral nutrition to enteral feeding and, thereby, normalize their lifestyle. Microsc. Res. Tech. 51:138–148, 2000. © 2000 Wiley-Liss, Inc.

Epidermal growth factor is critical for intestinal adaptation following small bowel resection

The loss of small intestinal mucosal surface area is a relatively common clinical situation seen in both the pediatric and adult population. The most frequent causes include mesenteric ischemia, trauma, inflammatory bowel disease, necrotizing enterocolitis, and volvulus. Following surgical resection, the remnant intestine compensates or adapts to the loss of native bowel by increasing its absorptive surface area and functional capacity. Unfortunately, many patients fail to adapt adequately, and are relegated to lifelong intravenous nutrition. Research into intestinal adaptation following small bowel resection (SBR) has evolved only recently from the gross and microscopic level to the biochemical and genetic level. As understanding of this process has increased, numerous therapeutic strategies to augment adaptation have been proposed. Epidermal growth factor (EGF) is an endogenous peptide that is secreted into the gastrointestinal tract and able to influence gut ontogeny, as well as mucosal healing. Early studies have demonstrated its ability to augment the adaptive process. Focusing on a murine model of massive intestinal loss, the morphological, structural, biochemical, and genetic changes that occur during the intestinal adaptive process will be reviewed. The role of EGF and its receptor as critical mediators of the adaptive process will be discussed. Additionally, the ability of EGF to augment intestinal proliferation and diminish programmed cell death (apoptosis) following SBR will be examined. Enhancing adaptation in a controlled manner may allow patients to transition off parenteral nutrition to enteral feeding and, thereby, normalize their lifestyle.

Changes in small intestinal structure and function in HIV-infected patients with chronic diarrhoea.

Human immunodeficiency virus (HIV) is often combined with unexplainable diarrhoea and weight loss. This study was designed to see if changes in the intestinal mucosal structure could explain the malabsorption found in HIV-infected patients with diarrhoea. Twenty acquired immunodeficiency system (AIDS) patients, 19 men and 1 woman, CD4 < 0.01, with severe weight loss and with non-infectious chronic diarrhoea, were evaluated using a new intestinal function test (D-xylose breath test). Fifteen of the subjects were examined with an upper intestinal endoscopy with biopsy specimens taken from the duodenal mucosa. The function test showed that the D-xylose uptake was markedly decreased to the same extent as for patients with coeliac disease (breath index AIDS patients 9.4 (4.3-14.4), coeliac patients 15.6 (7.6-23.6), reference level 2.5 (2.4-2.9), urine excretion AIDS patients 20% (13-26), coeliac patients 22% (14-24), reference level 37% (32-42)). The severe malabsorption could not be explained by the slight mucosal changes occasionally seen by light microscopy with small mucosal inflammation and almost normal villi. However, electron microscopy showed enterocytes with signs of hypofunction and degeneration correlating better to the intestinal malabsorption found in patients with advanced HIV infection and chronic diarrhoea.

Importance of milk and diet on the ontogeny and adaptation of the intestine.

Importance of milk and diet on the ontogeny and adaptation of the intestine.

Sequential changes in small intestinal structure and function during rotavirus infection in neonatal rats.

Rotavirus infection is the most common cause of acute diarrhoea in children worldwide. The structural and functional consequences of mammalian rotavirus infection in the small intestine have been incompletely studied and the mechanism of enterocyte damage poorly defined. This study used a neonatal rat model of group B rotavirus infection to study the natural history, clinical features, and the structural and functional consequences of infection in the small intestine. Group B rotavirus infection in eight day old neonatal rats produced diarrhoea by 24-36 hours, which was accompanied by weight loss during the early stages of infection. By seven days the diarrhoea had ceased and body weight was similar to noninfected controls. Rotavirus could be recovered in faeces from 24-72 hours. Light microscopy and morphometry confirmed reduction in villous height in both jejunum and ileum, with a reduction in total mucosal thickness indicating true flat mucosa. Increase in crypt depth followed villous shortening and continued as villous height progressively increased between 96-168 hours. Steady state perfusion of the entire small intestine with a plasma electrolyte solution confirmed the presence of a net secretory state for water between 12-48 hours, with a parallel reduction in sodium absorption. Group B rotavirus infection produces a self limiting acute diarrhoeal illness in neonatal rats similar to human rotavirus infection. Infection causes a reversible flat mucosa resulting from enterocyte loss associated with a net secretory state for water and impaired sodium absorption as a functional correlate. These findings may have relevance for the pathogenesis of human rotavirus infection.