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Necrotizing enterocolitis (NEC), a life-threatening intestinal disease, is becoming a larger proportionate cause of morbidity and mortality in premature infants. To date, therapeutic options remain elusive. Based on recent cell therapy studies, we investigated the effect of a human placental-derived stem cell (hPSC) therapy on intestinal damage in an experimental NEC rat pup model. NEC was induced in newborn Sprague-Dawley rat pups for 4 days via formula feeding, hypoxia, and LPS. NEC pups received intraperitoneal (ip) injections of either saline or hPSC (NEC-hPSC) at 32 and 56 h into NEC induction. At 4 days, intestinal macroscopic and histological damage, epithelial cell composition, and inflammatory marker expression of the ileum were assessed. Breastfed (BF) littermates were used as controls. NEC pups developed significant bowel dilation and fragility in the ileum. Further, NEC induced loss of normal villi-crypt morphology, disruption of epithelial proliferation and apoptosis, and loss of critical progenitor/stem cell and Paneth cell populations in the crypt. hPSC treatment improved macroscopic intestinal health with reduced ileal dilation and fragility. Histologically, hPSC administration had a significant reparative effect on the villi-crypt morphology and epithelium. In addition to a trend of decreased inflammatory marker expression, hPSC-NEC pups had increased epithelial proliferation and decreased apoptosis when compared with NEC littermates. Further, the intestinal stem cell and crypt niche that include Paneth cells, SOX9 + cells, and LGR5 + stem cells were restored with hPSC therapy. Together, these data demonstrate hPSC can promote epithelial healing of NEC intestinal damage. NEW & NOTEWORTHY These studies demonstrate a human placental-derived stem cell (hPSC) therapeutic strategy for necrotizing enterocolitis (NEC). In an experimental model of NEC, hPSC administration improved macroscopic intestinal health, ameliorated epithelial morphology, and supported the intestinal stem cell niche. Our data suggest that hPSC are a potential therapeutic approach to attenuate established intestinal NEC damage. Further, we show hPSC are a novel research tool that can be utilized to elucidate critical neonatal repair mechanisms to overcome NEC.

In children with autism spectrum disorder (ASD) who present to the gastroenterologist with chronic constipation on a background of colonic inflammation, we have identified two distinct clinical subtypes: (1) patients who experience a sustained state of GI symptomatic remission while on maintenance anti-inflammatory therapy (fast responders) and, (2) those with recurrent right-sided fecal loading requiring regular colon cleanouts during treatment for enterocolitis (slow responders). We hypothesized that a detailed molecular analysis of tissue from the affected region of the colon would provide mechanistic insights regarding the fast versus slow response to anti-inflammatory therapy. To test this, ascending colon biopsy tissues from 35 children with ASD (20 slow responders and 15 fast responders) were analyzed by RNAseq. Hierarchical cluster analysis was performed to assign samples to clusters and gene expression analysis was performed to identify differentially expressed transcripts (DETs) between samples within the clusters. Significant differences were found between the two clusters with fast responder-predominant cluster showing an upregulation of transcripts involved in the activation of immune and inflammatory response and the slow responder-predominant cluster showing significant over-representation of pathways impacting colonic motility (e.g. genes involved in tryptophan and serotonin degradation and mitochondrial dysfunction). Regression analysis identified a single long non-coding RNA that could predict cluster assignment with a high specificity (0.88), sensitivity (0.89) and accuracy (0.89). Comparison of gene expression profiles in the ascending colon from a subset of patients with ASD, chronic right-sided fecal loading constipation and a slow versus fast response to therapy has identified molecular mechanisms that likely contribute to this differential response following the primary therapeutic intervention (i.e. treatment for colonic inflammation with brief induction immunosuppression followed by maintenance non-steroidal anti-inflammatory therapy). Importantly, we have identified a transcript that, if validated, may provide a biomarker that can predict from the outset which patients will be slow responders who would benefit from an alternate therapeutic strategy in treating their constipation.

Introduction: Glucagon-like peptide-2 (GLP-2) is a known intestinal growth factor that enhances mucosal mass and function in residual small intestine after massive small bowel resection (MSBR). Luminal omega-3 (OM-3) has been shown to have some growth factor properties. It is possible that their mechanisms of action differ. Thus, we hypothesized that administering these two substances together may have a synergistic effect., Methods: A total of 60 adult female Sprague-Dawley rats underwent 80% MSBR and divided as follows (n = 15/group): Saline (Control) + regular feeds; GLP-2 + regular feeds; Saline + OM-3 enriched feeds; and GLP-2 + OM-3 enriched feeds. Five animals per group were sacrificed at 7, 14, and 28 days. Small intestine mucosa was harvested. DNA and protein content were measured (mucosal mass markers) at all three time points. Galactose and Glycine absorption were measured (functional capacity markers) at 28 days. Statistical analysis was done by ANOVA with post hoc Tukey's HSD test., Results: At all three time points, DNA was increased in all treatment groups compared to control (P < 0.05), but GLP-2 + OM-3 group did not have increased DNA content when compared to either treatments alone. At 7 and 14 d, all three treatment groups had increased protein content compared to control (P < 0.05). At 28 d, GLP-2 + OM-3 did not have increased protein content compared to control or individual treatments (P < 1.0). All three treatment groups had increased absorption of galactose and glycine compared to control (P < 0.05) but not each other., Conclusions: Individually, GLP-2 and OM-3 are very effective in enhancing the adaptive process by increasing mucosal mass and function, at all three time points. More importantly, clinically, GLP-2 and OM-3 increase substrate absorption in a rat model of intestinal failure. However, the combination is not synergistic., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: For patients with intestinal failure, parenteral nutrition (PN) is a life-saving therapy. Unfortunately, hepatic dysfunction will occur in 40 to 60% of children on long-term PN. While the hepatic dysfunction is likely multifactorial, one important chemical component of the disease may be aluminum contamination of the PN. Previous studies have shown a reduction in liver injury by decreasing the aluminum concentration in PN in a pig model. We sought to develop a rat model of PN-associated liver disease (PNALD) with parenteral aluminum., Methods: Adult Sprague-Dawley rats had intravenous long-term catheters placed. The control group underwent daily injections of saline. The study rats had daily injections of either 2 or 3 mg/kg aluminum chloride (AlCl3). At the end of 4 weeks, the rats were euthanized and liver and blood samples were taken. The livers were analyzed and graded by a pathologist for histological evidence of liver degeneration and acute and chronic inflammation. The serum was analyzed for total bilirubin, alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)., Results: There was no difference in serum values of total bilirubin, alkaline phosphatase, ALT, or AST. There was no difference in acute inflammation among the groups (1 [control], 1.2 [2 mg/kg], 1.1 [3 mg/kg]). The rats treated with parenteral aluminum had significantly more Kupffer cells than the control group (0.1 [control], 3 [2 mg/kg], 2.2 [3 mg/kg], p < 0.0001 [control vs. 2 mg/kg] and 0.0032 [control vs. 3 mg/kg]). There was also more liver degeneration in the parenteral aluminum groups than the control group (1 [control], 2 [2 mg/kg], 2.5 [3 mg/kg], p = 0.0341 [control vs. 2 mg/kg] and 0.009 [control vs. 3 mg/kg]). However, there was no difference between 2 and 3 mg/kg AlCl3 for either variable., Conclusion: This study suggests that 4 weeks of parenteral aluminum can induce chronic inflammation and degeneration of the liver in rats. Therefore, we believe that daily injections of parenteral aluminum can produce a viable model of PNALD in rats. However, further studies are warranted, including measurement of serum aluminum levels in infants on PN., (Georg Thieme Verlag KG Stuttgart · New York.)

Immediate operative exploration has been considered mandatory for all penetrating injuries to Zone II of the neck and in any patient who is unstable, regardless of the location of the injury. We report two cases of penetrating carotid artery injuries in children successfully managed with endovascularly placed covered stents. These cases demonstrate that endovascular carotid artery repair can be considered in children, including in patients with Zone II injuries and in initially unstable patients.

Purpose: Necrotizing enterocolitis (NEC) requiring surgical intervention is associated with mortality rates approaching 50%. We evaluated outcomes of patients that underwent surgical treatment for NEC with vacuum-assisted closure (VAC) of the abdomen as compared with traditional laparotomy, bowel resection, and ostomy creation., Methods: A retrospective review identified 26 patients from 2007 to 2012 with NEC. Overall, 17 patients were treated with laparotomy, and 9 were treated with laparotomy and VAC (LapVac). Age, weight, preoperative and postoperative mean airway pressure, length of bowel resected, duration on total peripheral nutrition, time until initiation of feeds, and length of stay were assessed. A Student's t-test was used for statistical analysis., Results: Nine LapVac patients underwent a total of 1.2 ± 1.3 VAC changes and had open abdomens for 13.1 ± 19.1 days. LapVac and traditional laparotomy patients had similar outcomes with respect to amount of bowel resected, time on a ventilator, time to initiation of feeds, and length of hospital stay. Two of nine patients (22%) in the LapVac group were placed in continuity without the need for an ostomy. We identified a subset of patients in the LapVac group that demonstrated signs of abdominal compartment syndrome (ACS), exhibiting mean airway pressures greater than 15 cm H2O preoperatively. Patients with ACS treated with VAC therapy had shorter time to initiation of feeds (p=0.047) and shorter lengths of stay (p=0.0395) as compared with traditional laparotomy., Conclusion: Our data demonstrate that use of the wound VAC is a safe approach in the management of premature infants with NEC requiring surgical intervention with outcomes comparable to standard surgical management. Use of the wound VAC may allow the establishment of bowel continuity and abdominal closure without the need for an ostomy. VAC therapy may also hasten the recovery of NEC patients with concomitant ACS by eliminating the compartment syndrome. Larger studies are required to confirm this theory., (Georg Thieme Verlag KG Stuttgart · New York.)

Following the promising multicenter randomized trial results of in utero fetal myelomeningocele repair; we anticipate that an increasing number of tertiary care centers may want to offer this therapy. It is essential to establish minimum criteria for centers providing open fetal myelomeningocele repair to ensure optimal maternal and fetal/pediatric outcomes, as well as patient safety both short- and long-term; and to advance our knowledge of the role and benefit of fetal surgery in the management of fetal myelomeningocele. The fetal myelomeningocele Maternal-Fetal Management Task Force was initially convened by the Eunice Kennedy Shriver National Institute of Child Health and Human Development to discuss the implementation of maternal fetal surgery for myelomeningocele. The decision was made to develop the optimal practice criteria presented in this document for the purpose of medical and surgical leadership. These criteria are not intended to be used for legal or regulatory purposes., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Short bowel syndrome (SBS) is the most common cause of intestinal failure in children. It is defined as the inability to maintain adequate nutrition enterally as a result of a major loss of the small intestine. SBS is a life-threatening entity associated with potential significant morbidity and mortality. The etiology in the pediatric age group includes necrotizing enterocolitis (32%), atresia (20%), volvulus (18%), gastroschisis (17%), and aganglionosis (6%). It is characterized by substrate malabsorption, electrolyte imbalance, intestinal bacterial overgrowth, steatorrhea, and weight loss. Current medical management includes parenteral nutrition, progressive feeds as tolerated, various medications, and surgical manipulations. However, frequently this management is not successful in achieving the goal of attaining normal growth and development without parenteral nutrition. It has been known for decades that there is a normal physiologic response of the residual intestine to massive bowel resection referred to as intestinal adaptation. The mechanisms that control this process are unknown. Unfortunately, intestinal adaptation and the current management are not always successful. As a result of new knowledge regarding the pathophysiology of SBS over the past two decades, several novel strategies have been developed in experimental animal models as well as limited clinical trials in infants and children. They can be divided into several categories that potentially influence intestinal (1) absorption, (2) secretion, (3) motility, and (4) adaptation. More recently, newer modalities have been studied including small intestine transplantation, and the use of specific intestinal growth factors. Ultimately, tissue and organ engineering will become the treatment for infants and children with SBS.

Currently, in the United States there is a significant physician workforce shortage. This problem is likely to persist as there is no quick solution. The nature of this shortage is complex and involves factors such as an absolute physician shortage, as well as physician shortages in primary care and certain specialty care areas. In addition, there is a misdistribution of physicians to medically underserved areas and populations. The medical education system trains medical school graduates that eventually feed the physician workforce. However, several factors are in place which ultimately limits the effectiveness of this system in providing an appropriate workforce to meet the population demands. For-profit medical schools have been in existence in and around the continental US for many years and some authors have suggested that they may be a major contributor to the physician workforce shortage. There is currently one for-profit medical school in the US, however the majority exist in the Caribbean. The enrollment in and number of these schools have grown to partially meet the ever-growing demand for an increase in medical school graduates and they continue to provide a large number of graduates who return to the US for postgraduate medical training and, ultimately, increase the physician workforce. The question is whether this source will benefit the workforce quality and quantity needs of our growing and aging population.

Background: We have previously shown that there is synergism between Hepatocyte Growth Factor (HGF) and Omega-3 (OM-3) enriched feeds using an immunologic model of inflammatory bowel disease (IBD). This combination decreased inflammation and cytokine levels and increased microvascular density and mucosal mass. This study evaluates the gene alterations that occurred using this same model., Methods: Twenty adult female transgenic HLA-B27 rats were divided into four groups: Group 1: (Regular feeds, IV saline); Group 2: (OM-3 feeds, IV saline); Group 3: (Regular feeds, IV HGF 150 μg/kg/day); Group 4: (OM-3 feeds, IV HGF 150 μg/kg/day). Rats were sacrificed 14 days after pump placement. Bowel was harvested and RNA extracted. Microarray gene chips were used. Statistical analysis was done by analysis of variance using Partek Genomics Suite. Results were significant if fold change was more than 2 or less than -2, with P<0.05., Results: In the ileum, HGF up- or down-regulated 34 genes, while OM-3 affected 60 genes. Together 68 genes were affected. Families with a synergistic effect included Solute Carrier Proteins, ATP Binding Cassette Proteins, and Matrix Metalloproteinases. In the colon, 23 genes were affected by HGF, while 66 genes were affected with OM-3. Combined exposure affected 32 genes, including a synergistic effect on solute carrier proteins, aquaporins, and immunologic factors., Conclusions: There is a synergistic gene alteration effect of exposure of two (HGF and Omega-3 enriched feeds) agents on bowel mucosa. Of most interest was the synergistic effect on the solute carrier protein family, a previously identified gene family up-regulated in response to intestinal failure., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Pulmonary sequestration is a rare congenital pulmonary malformation. We report a case of a 10-month-old infant with intralobar pulmonary sequestration diagnosed in utero. The lesion had an uncommon blood supply consisting of three large arteries deriving from the thoracic aorta and venous drainage into the inferior vena cava.

Background: Single-incision pediatric endosurgery is gaining popularity, especially for abdominal operations. Several reports in the literature support the feasibility of the single-incision approach in pediatric laparoscopy. Here we compare our experience with single-incision thoracoscopic surgery (SITS) to traditional multiple-incision video-assisted thoracoscopic surgery (VATS) in children., Methods: A chart review of all patients who underwent SITS at our institution was performed. The same number of demographically matched VATS case controls were selected from a pool of patients operated on during the same time period. Operative time, time until chest tube removal, length of stay, complications, and any need for further intervention were recorded. Statistical analysis was done by Student's t-test using Instat 3., Results: Fourteen SITS procedures were performed during the study period. These patients were compared with 14 VATS case controls. Both groups were similar with regard to age, weight, sex, and procedures performed. The mean operative time in the SITS group was 84 ± 43 minutes versus 64 ± 30 in the VATS group (P=.18). Days until chest tube removal was 4 ± 2.2 in the SITS group and 2.8 ± 1.4 in the VATS group (P=.09). Length of hospital stay was 5.5 ± 4.4 days in the SITS group versus 7.2 ± 8.6 in the VATS group (P=.51). There were no intraoperative complications and no procedure conversions in either group. One SITS patient who underwent a wedge resection and mechanical pleurodesis for a spontaneous pneumothorax was readmitted for a recurrent pneumothorax and required a reoperation., Conclusions: Our experience demonstrates that there are no statistically significant differences in operative time, time until chest tube removal, and length of hospital stay when comparing SITS to VATS in children. We believe that SITS is an equivalent procedure that allows for fewer scars when compared with traditional multiple-incision VATS in children.

Background: The management of lymphangiomas in children is a complex problem with frequent recurrence and infection. Vacuum-assisted closure (VAC) devices have been shown to accelerate the healing of open wounds. We hypothesized that VAC therapy might decrease complications after resection of lymphangiomas., Methods: A retrospective review was performed on 13 children (August 2005 to April 2010) who were patients undergoing lymphangioma resection with postoperative VAC therapy. Patient demographics, size and location of the lymphangioma, VAC duration and number of changes, hospital stay, complications, need for further surgery, and length of follow-up were recorded., Results: Thirteen children (mean age, 8 years; mean weight, 34 kg) underwent 15 operations for lymphangiomas followed by postoperative VAC therapy. Locations included the head and neck, thorax and abdomen, and lower extremity. The mean VAC duration was 19 days, and they underwent a mean of 2.6 VAC changes. Six children had operative closure of the wound at a mean of 15 days postoperative. The remaining patients underwent closure by secondary intention. There were no recurrences. Complications included VAC device malfunctions requiring intervention and wound infections. Mean follow-up was 289 days., Conclusion: Postoperative VAC therapy for the treatment of lymphangiomas can be an effective adjunct to surgical treatment by decreasing risks of recurrence and infection., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Hepatocyte growth factor (HGF) decreases intestinal inflammation and cytokine levels in an animal model of inflammatory bowel disease (IBD). Luminal omega-3 (OM-3) is anti-angiogenic, reduces inflammation, and may decrease symptoms in patients with Crohn's disease. This study evaluates the synergism of HGF and OM-3., Methods: Twenty adult female transgenic HLA-B27 rats were divided into 4 groups: group 1: regular feeds, IV saline; group 2: OM-3-enriched feeds, IV saline; group 3: regular feeds, IV HGF (150 µg/kg per day); and group 4: OM-3-enriched feeds, IV HGF(150 µg/kg per day). Rats were killed at 14 days after pump placement. Small and large bowel mucosa was harvested, and DNA and protein were extracted and quantified. Statistical analysis was done by analysis of variance with post-hoc Tukey's HSD test., Results: Content of protein and DNA in the ileum were significantly increased by supplementation of HGF (P < .001, P < .01, respectively) alone. OM-3 significantly increased protein content but not DNA (P = .02, P = 0.3, respectively). Combined, they had a synergistic effect greater than either supplement alone (P = .0001, P = .002, respectively). In the colon, HGF and OM-3 did not significantly increase protein or DNA content individually or together., Conclusions: This is the first demonstration of the synergistic effect of a growth factor (HGF) and a dietary supplement (OM-3) in an immunologic model of IBD., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: We previously demonstrated that hepatocyte growth factor (HGF) increases mucosal protein and DNA content at single time points during intestinal adaptation in rats. This study evaluates mucosal changes after massive small bowel resection (MSBR) and with the addition of IV HGF measured over the timeframe of intestinal adaptation., Methods: Sixty adult female Sprague-Dawley rats were divided into three groups and underwent massive small bowel resection (MSBR), MSBR+HGF (intravenous 150 mg/kg/d), or sham operation (control). Five animals per group were sacrificed at 7, 14, 21, and 28 d. Ileal mucosa was harvested and DNA and protein extracted. DNA content (ug/mg mucosa) was measured at 260 nm and protein content (ug/mg mucosa) was measured using the Bradford assay. MIB-5 immunohistochemical staining was done to confirm that the increased DNA content was due to proliferation. Statistical analysis was by ANOVA with post-hoc Tukey's HSD test., Results: At 7 and 14 d, protein concentration was increased following HGF administration in comparison to MSBR alone and in control rats (P<0.05 and P<0.03, respectively). Mucosal DNA content in the MSBR-HGF rats was significantly increased over MSBR and control groups at 21 and 28 d (P<0.02 and P<0.004, respectively). MIB-5 immunohistochemical staining correlated with mucosal DNA content at 21 and 28 d (P<0.0005 and P<0.002, respectively)., Conclusions: The mucosal response to MSBR for the period 7-14 d after surgery demonstrates that protein content is increased due to an emphasis on hypertrophy, whereas at 21-28 d hyperplasia is the primary change as demonstrated by the increase in DNA content. This response was enhanced by HGF. This is the first demonstration correlating the bimodal gene response during intestinal adaptation to the bimodal mucosal response. Also, this is the first demonstration of a biphasic response by the mucosa to HGF during intestinal adaptation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Although laparoscopic pyloromyotomy is considered to be a clean case, many surgeons administer prophylactic preoperative antibiotics. The aim of this study was to evaluate the impact of prophylactic antibiotics on the wound infection rate after laparoscopic pyloromyotomy., Methods: We conducted a retrospective review of all patients who underwent laparoscopic pyloromyotomy at our institution between August 2002 and December 2009. Data included patient age, sex, weight, serum HCO(3) at admission and at operation, and if the patient received prophylactic antibiotics. The rate of wound infection or other wound complications, including suture granuloma, umbilical granuloma, umbilical hernia, skin dehiscence, and omental evisceration, was determined., Results: Two hundred ninety-nine patients underwent 301 consecutive laparoscopic pyloromyotomies. Sixty-four percent (n = 194) of patients returned for follow-up and were included in the study. Fifty-seven percent (group A, n = 111) received antibiotics, and 43% (group B, n = 84) did not. There were 3 wound infections in each of the equally matched groups (group A, 2.7%; group B, 3.5%; P = .73). Other wound complications occurred in 4.5% of patients (n = 5) in group A and 8.3% of patients (n = 7) in group B (P = .27)., Conclusion: The use of prophylactic antibiotics does not significantly decrease the rate of wound infection or other wound complications after laparoscopic pyloromyotomy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Single-incision pediatric endosurgery is gaining popularity in children. We have recently applied the single-incision approach for thoracoscopic procedures. We report our initial experience with single-incision thoracoscopic surgery in the pediatric population., Methods: A retrospective chart review of the first 10 single-incision thoracoscopic operations done at our institution was conducted. The patients' mean age and weight and the median operative time, postoperative length of stay, and time until discontinuation of chest tubes were determined., Results: The 10 procedures were performed in eight patients (two patients each had bilateral procedures). The procedures performed included wedge resection and mechanical pleurodesis for spontaneous pneumothorax (n = 7), wedge biopsies for lymphoma (n = 1) and chronic granulomatous disease (n = 1), and resection of an apical extrapulmonary neuroblastoma (n = 1). All of the procedures were completed without intraoperative complication or significant blood loss. In each case, multiple trocars and/or unsheathed instruments were passed through a single small incision, which was subsequently used for the chest tube(s). The mean patient age was 13.5 years (range 3-18 years). The mean weight was 47 kilograms (range 16-63 kg). The median operative time was 64 minutes (range 50-201 minutes). The median postoperative length of stay was 7 days (range 3-19 days). The median time until chest tube removal was 3 days (range 2-15 days). The mean follow-up was 7 months (range 3-12 months). One patient developed a recurrent pneumothorax and persistent air leak after having undergone a wedge resection and pleurodesis for a spontaneous pneumothorax and required a reoperation., Conclusion: Single-incision thoracoscopic surgery is a feasible alternative to the traditional multiple-incision approach in the pediatric population. The in-line positioning of the camera and instruments often proves to be an advantage rather than a hindrance.

Purpose: Previously, we investigated the physiologic effects of hepatocyte growth factor (HGF) on intestinal adaptation using a massive small bowel resection (MSBR) rat model. To correlate these altered physiologic changes with gene alterations, we used microarray technology at 7, 14, and 21 days after MSBR., Methods: Forty-five adult female rats were divided into 3 groups and underwent 70% MSBR, MSBR + HGF (intravenous 150 μg/kg per day), or sham operation (control). Five animals per group were killed at each time point. Ileal mucosa was harvested and RNA extracted. Rat Gene Chips and Expression Console software (Affymetrix, Santa Clara, CA) were used. Statistical analysis was done by analysis of variance using Partek Genomics Suite (Partek, Inc, St Louis, MO). Results were significant if fold change was more than 2 or less than -2, with P < .05., Results: Compared with the control group, MSBR group had significant increases in up-regulated and down-regulated genes. The MSBR-HGF group had further increases in up-regulated and down-regulated genes compared with the MSBR group. At 7 days, 6 cellular hypertrophy families had 30 genes up-regulated, and HGF up-regulated an additional 14 genes. At 21 days, 5 hyperplasia gene families had 32 up-regulated genes. Hepatocyte growth factor up-regulated an additional 16 genes., Conclusions: Microarray analysis of intestinal adaptation identified an early emphasis on hypertrophy and later emphasis on hyperplasia. This is the first demonstration that the effect of HGF on intestinal adaptation is recruitment of more genes rather than an increase in the fold change of already up-regulated genes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Total parenteral nutrition (TPN) induced liver failure is the leading indication for transplantation in children. Our previous research demonstrated the benefit of a specific intravenous dose of hepatocyte growth factor (HGF) in the amelioration of TPN-induced liver injury. This study was designed to ascertain the optimum concentration of HGF in an animal model of TPN-induced liver injury., Materials and Methods: Twenty adult female Sprague-Dawley rats underwent 70% small bowel resection and placement of venous catheters connected to subcutaneous osmotic minipumps. Four groups (n=5 each) based on the contents of the osmotic pump were utilized as follows: group 1 (control): saline; group 2: HGF 75 mcg/kg/d; group 3: HGF 150 mcg/kg/d; and group 4: HGF 250 mcg/kg/d. Each rat received 14 d of TPN without enteral nutrition. After sacrifice, the liver was harvested. Hepatic inflammation was evaluated using antibodies for TNF-α and IL-6. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technique., Results: All concentrations induced statistically significantly less IL-6 and TNF- α expression compared to the control animals. Increased efficacy was demonstrated with increasing dose concentration up to 150 mcg/kg/d but not 250 mcg/kg/d. Apoptotic activity was decreased statistically significantly for all dose concentrations compared with the controls, as well as to increases in dose concentration., Conclusions: Increasing concentrations of HGF were directly correlated with increased modulation of inflammatory response and apoptotic index in this animal model for TPN-induced liver injury, up to 150 mcg/kg/d. Further increases were significant with respect to apoptotic index only. Further investigations are warranted to determine if HGF may be useful to minimize TPN-induced liver injury in children., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to compare outcomes after laparoscopic and open techniques for Nissen fundoplication and gastrostomy placement in the neonatal intensive care unit (NICU) population., Methods: The medical records for NICU inpatients who underwent laparoscopic and open Nissen fundoplication and gastrostomy placement from August 2002 to August 2008 were reviewed after Institutional Review Board approval. Each technique was compared with regard to operative time, estimated blood loss, postoperative 24-hour narcotic requirements, time to goal feeds, and complication rates. Analysis of variance was used to determine statistical significance. Data are quoted as mean +/- SEM., Results: Fifty-seven NICU patients underwent fundoplication and gastrostomy placement (25 laparoscopic and 32 open). The time to goal feeds was significantly shorter for the laparoscopic group (4.3 +/- 0.4 vs 6.1 +/- 0.6 days, P = .04). The 24-hour postoperative narcotic requirement was significantly lower in the laparoscopic group (0.24 +/- 0.05 vs 0.55 +/- 0.08 mg/kg, P = .007). Operation times (111 +/- 5 [open] vs 113 +/- 5 minutes, P = .76) and estimated blood loss (13 +/- 2 [open] vs 11 +/- 1 mL, P = .33) were comparable for both groups., Conclusion: Laparoscopic and open techniques for Nissen fundoplication with gastrostomy placement are safe and appropriate treatment methods with equivalent operating times for the treatment of gastroesophageal reflux in the NICU population., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: Dependence on total parenteral nutrition in intestinal failure or short bowel syndrome patients can lead to many complications. The most significant complication is progressive liver injury leading to liver failure. This study assesses the potential of hepatocyte growth factor (HGF) in modulating the hepatic response in a rat cholestatic liver injury model., Methods: Female Sprague-Dawley rats were divided into 3 groups: control (n = 5), chronic liver injury (alpha-naphtylisocyocyanate [ANIT] every 3.5 days at 75 mg/kg; n = 5), and chronic liver injury plus HGF (ANIT + HGF at 250 microg kg(-1) d(-1); n = 5). The rats initially underwent massive (80%) small bowel resections. Seven days later, they were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic minipump for continuous intravenous saline or HGF. Intraperitoneal saline or ANIT injections were subsequently administered every 3.5 days to create a chronic cholestatic model. After 14 days, the animals were euthanized, and liver biopsies were obtained. The liver biopsies were evaluated by histology, immunofluorescence staining for interleukin-6 and tumor necrosis factor alpha, and assessment of apoptosis by terminal dUTP-transferase-mediated nick end labeling (TUNEL) technique., Results: In this chronic liver injury model, HGF did not effect the grade of inflammation. However, HGF did induce retention of the ductal structures and avoided ductal proliferation, damage, and evidence of primary sclerosing cholangitis (P < .05). Hepatocyte growth factor induced less interleukin-6 (P < .011) and tumor necrosis factor alpha (P < .01) expression. Apoptotic activity was also significantly less in the HGF group (P < .01)., Conclusion: Hepatocyte growth factor preserved the hepatic ductal system, modulated the hepatic inflammatory response, and reduced the apoptotic index in this chronic cholestatic liver injury model. It may diminish or prevent liver damage in patients with total parenteral nutrition-induced liver injury., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Using the transgenic HLA-B27 rat model of inflammatory bowel disease (IBD), we have previously demonstrated hepatocyte growth factor's (HGF) potential to ameliorate diarrhea and decrease bowel injury. This study was designed to assess the effect of HGF on the neovascularization and inflammation in IBD., Materials and Methods: Female transgenic HLA-B27 rats were divided into two groups: group 1, saline (control, n = 6); group 2, HGF (150 mug/kg/d, n = 9). Treatments were delivered into the jugular vein via a 14-d subcutaneously placed osmotic mini-pump. Intestinal microvascular density (MVD), histologic inflammatory score, inflammatory cell infiltration, and cytokine expression (tumor necrosis factor-alpha {TNF-alpha}, interferon-gamma {IFN-gamma}, and interleuken-2 {IL-2}) were assessed. Analysis of variance (ANOVA) was used to determine statistical significance., Results: Administration of HGF resulted in variable but significant alterations in ileal and colonic histology compared with control animals. Compared with group 1, inflammatory cell infiltration was significantly reduced in group 2 (7.7 +/- 1.2 versus 13.3 +/- 2.1 SEM, P < 0.05). Enzyme linked immunosorbent assays (ELISA) demonstrated significantly less expression of ileal IFN-gamma, ileal IL-2 and colonic IL-2 in group 2 (P < 0.05) (Fig. 1). Of importance is that Group 2 exhibited significantly greater MVD in the ileum and colon, both P < 0.05 (Figs. 2 and 3)., Conclusion: HGF stimulates neovascularization while modulating the intestinal inflammatory response. This is the first demonstration in which a growth factor (HGF) stimulates nonpathologic angiogenesis in an animal model of IBD. HGF administration may be beneficial in the clinical management of IBD.

Inherited thrombophilia, a predisposition for a hypercoagulable state, has been associated with cases of intestinal atresia. In this communication, we report a case of terminal ileal atresia and total colonic aganglionosis (Hirschsprung's disease), a rarely documented association, in a neonate who seemed to have a hypercoagulable state. The case stresses the need for recognition of this sequence of events in order to achieve optimal management.

Background/purpose: The major side effect of total parenteral nutrition is liver injury leading to liver failure. This study was designed to assess specific growth factors in modulating the hepatic response in an ANIT-induced liver-injury model., Methods: Sprague-Dawley rats were divided into four groups: control (n = 5), liver-injury control (alpha-naphthylisothiocyanate [ANIT], 100 mg/kg, n = 8), ANIT + epidermal growth factor (EGF, 150 mug/kg per day, n = 10), and ANIT + hepatocyte growth factor (HGF, 250 mug/kg per day, n = 9). Rats were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic mini-pump for 7 days of continuous intravenous saline (liver injury control), EGF, or HGF. Seven and 14 days later, liver biopsies were obtained and evaluated for interleukin (IL)-6 and tumor necrosis factor alpha expression by immunofluorescent staining, and for apoptosis, by the terminal transferase dUTP nick end labeling (TUNEL) technique. All animals were euthanized at 14 days., Results: Epidermal growth factor (P < .025) and HGF (P < .001) groups induced less IL-6 expression at day 14 compared to liver-injury controls. In addition, the interval decrease in IL-6 expression between days 7 and 14 was greater in EGF (P < .001) and HGF (P < .001) groups compared to liver-injury controls. At day 14, HGF also demonstrated decreased tumor necrosis factor alpha expression (P < .005). Apoptotic activity was significantly less for the EGF (P < .011) and HGF (P < .0012) groups., Conclusion: Epidermal growth factor and HGF modulated the hepatic inflammatory response and apoptotic index in this established liver-injury model and may diminish or prevent liver damage in patients with total parenteral nutrition-induced liver injury.

This communication describes the histological, immunohistochemical, ultrastructural, and cytogenetic study of an ovarian sclerosing stromal tumor resected from a 7-month-old girl who presented with vaginal bleeding. The tumor is very rare, its pathogenesis is not clear, and its hormonal activity has been subject to debate. In addition, it has been rarely seen in children and never in infants, with the youngest patient reported being 10 years of age. Histological study of the tumor showed a process of multinodular asynchronous growth followed by gradual loss of cells, hyalinization, and eventual transformation into corpora albicantia-like structures, thus indicating that the process may be more akin to an ovarian nodular follicular hyperplasia than to a classical neoplasm. The study also documented an elevated proliferative MIB-1 index in the process, which had not been investigated in earlier reports, and illustrated the immunohistochemical reactivity of some of its stromal cells to progesterone receptors.

Ovarian sex cord stromal tumor (OSCST), sclerosing type, is an extremely rare ovarian tumor. Sex hormone production by OSCST can result in isosexual or heterosexual precocious puberty in younger patients. We present a case of a 7-month-old female infant found to have a sclerosing-type OSCST that presented with vaginal bleeding and very prominent vellus hair at the mons pubis. This represents the youngest patient reported in the literature with this subset of OSCST.

Background: The administration of hepatocyte growth factor (HGF) during intestinal adaptation is known to enhance intestinal adaptation. Glucagon has also been implicated as a potential mediator of intestinal adaptation. Previous studies have shown that HGF and glucagon synergistically increase the proliferation of hepatocytes. HGF has also been shown to be preferentially expressed within the glucagon-positive cells of the pancreas, possibly indicating a paracrine or endocrine effect of HGF on glucagon. This study was designed to determine if HGF stimulation in the small intestine during intestinal adaptation influenced mucosal glucagon expression., Methods: Adult male Sprague-Dawley rats were randomized to either a 70% massive small bowel resection group (MSBR) or an HGF-treated MSBR group (MSBR-HGF). Seven days after surgery, HGF was administered intravenously at 150 mug/kg per day for 14 days. At day 21, the ileal and jejunal mucosa was harvested. The RAE 230A GeneChip (Affymetrix, Santa Clara, Calif) and MAS5 software were used to determine alterations in gene expression in the small intestine mucosa. Immunofluorescent staining of the ileal and jejunal mucosa using an antiglucagon antibody was performed and evaluated qualitatively., Results: The MSBR-HGF group had significantly greater protein and DNA content (P < .05) than the MSBR group. Glucagon gene expression in the MSBR-HGF group was decreased compared with the MSBR group, and immunohistostaining for glucagon in the ileum revealed no difference in intensity between the 2 groups. However, the jejunal MSBR-HGF group demonstrated significantly greater glucagon immunoreactivity than the jejunal MSBR group., Conclusion: Our data suggest that the HGF-induced increase in glucagon availability is disassociated from glucagon gene up-regulation. Thus, HGF may not only enhance intestinal adaptation directly, but also indirectly by increasing the "local" availability of other growth factors in the absence of their gene up-regulation.

Background/purpose: The mechanisms that control intestinal adaptation remain unknown. To better understand the adaptive process, microarray technology was used to analyze gene expression in a rat model of intestinal adaptation., Methods: Adult male Sprague-Dawley rats underwent either a massive small bowel resection (70%) with anastomosis or a sham operation with small bowel transection and reanastomosis. After 21 days, ileal mucosa RNA was extracted. Individual RNA samples (n = 5 per group) were labeled and hybridized to 10 separate RAE 230A rat GeneChips. The signal values were calculated and the 2 groups were compared using a t test with the multiple testing correction of Benjamini and Hochberg (false discovery rate of 10%). Probe sets were analyzed for overrepresented physiologic pathways using Expression Analysis Systematic Explorer (EASE)., Results: Of the 15,866 probe sets on the RAE 230A GeneChip, 5437 probe sets were unexpressed and excluded. Of the remaining 10,429 probe sets, several overrepresented pathways (EASE score <0.01 after Bonferroni correction) were identified. Further analysis revealed that 13 probe sets related to proteasome degradation (an enzyme complex implicated in the regulation of cell proliferation) were significantly upregulated in the intestinal adaptation group compared to the sham group., Conclusions: Proteasomes may play a critical role in regulating the proliferation of intestinal mucosa during intestinal adaptation.

Background/purpose: Glucagonlike peptide-2alpha (GLP-2alpha) has been shown to be a growth factor for the small intestine. This study investigated the benefits of intravenous and intraluminal administration of GLP-2alpha using a rat model of inflammatory bowel disease (IBD)., Methods: Normal Fisher rats and HLA-B27 (IBD) rats were treated for 14 days as follows: Fisher, intravenous saline (n = 6); HLA-B27, intravenous saline (n = 6); HLA-B27, intravenous GLP-2alpha (50 microg/kg/d; n = 5); Fisher, intraluminal saline (n = 5); HLA-B27, intraluminal saline (n = 5); or intraluminal GLP-2alpha (50 microg/kg/d; n = 5). Rats were evaluated for frequency of diarrhea, and the bowel was analyzed for gross and microscopic lesions. Statistical evaluations were determined using analysis of variance (ANOVA). A P value of.05 was significant., Results: Intravenous GLP-2alpha decreased diarrhea and the number of bowel lesions (P <.05). Microscopic inflammation was reduced by 24% but was not statistically significant. Intraluminal GLP-2alpha decreased the number of small intestine lesions (P <.05) and the microscopic inflammation (P <.05) but did not significantly reduce diarrhea or the overall number of bowel lesions., Conclusions: GLP-2alpha ameliorates the signs of IBD in HLA-B27 rats. Intravenous GLP-2alpha reduces diarrhea more effectively than intraluminal administration, and both routes are equally effective in ameliorating inflammation. GLP-2alpha potentially provides a new modality for the treatment of IBD.

Background/purpose: Transfection of the HLA-B27 gene into normal Fischer rats induces phenotypic changes similar to inflammatory bowel disease (IBD). This study investigated the benefits of 2 doses of hepatocyte growth factor (HGF) on the manifestations of IBD in this rat model., Methods: Fischer rats and HLA-B27 rats were divided into 4 groups: Fischer rats treated with saline, HLA-B27 rats treated with saline, HGF at 150 microg/kg/d, and HGF at 300 microg/kg/d. HGF or saline was infused for 14 days via an osmotic pump attached to a catheter in the internal jugular vein. After treatment, rats were evaluated for diarrhea and reduction in gross and microscopic bowel inflammation. Statistics were determined using analysis of variance (ANOVA). A P value < or =.05 was considered significant., Results: Administration of HGF at 150 microg/kg/d decreased diarrhea by 40%, gross inflammation by 41%, and microscopic inflammation by 72% (P < or =.05). At 300 microg/kg/d HGF decreased diarrhea by 46%, gross inflammation by 45%, and microscopic inflammation by 54% (P < or =.05)., Conclusions: HGF administration reduces the clinical manifestations of IBD in this rat model. Similar effects were seen at both doses of HGF administration, implying that there is a plateau above which further increases in HGF levels provides no added benefit. HGF administration may be clinically useful in the management of IBD.

This study was designed to investigate the benefits of administration of hepatocyte growth factor in a rat model of inflammatory bowel disease. Transfection of the HLA-B27 gene into Fisher rats induces a phenotype similar to inflammatory bowel disease. Fisher rats and HLA-B27 rats were divided into six groups: (1) Fisher, intravenous saline; (2) HLA-B27, intravenous saline; (3) HLA-B27, intravenous hepatocyte growth factor; (4) Fisher, luminal saline; (5) HLA-B27, luminal saline; and (6) HLA-B27, luminal hepatocyte growth factor. Rats received a 14-day infusion through an osmotic pump attached to a catheter positioned in either the jugular vein or the terminal ileum. Rats were evaluated for stool character, and gross and microscopic bowel inflammation. Statistics were analyzed using analysis of variance or the Kruskal-Wallis nonparametric test. A value of P<0.05 was significant. Compared to untreated HLA-B27 rats, intravenous administration of hepatocyte growth factor decreased diarrhea by 41% and microscopic inflammation by 54% (P<0.05). Luminal hepatocyte growth factor exposure decreased total bowel lesions by 53% and microscopic inflammation by 40% compared to untreated HLA-B27 rats (P<0.05), but it did not have an effect on diarrhea. Administration of hepatocyte growth factor ameliorates many of the features of bowel disease in this rat model and theoretically could have therapeutic applications in the management of inflammatory bowel disease in humans.

Background: Intestinal ischemia-reperfusion (IR) injury results in enterocyte necrosis and apoptosis. This study was designed to evaluate the potential protective effects of interleukin-11 (IL-11) pretreatment on intestinal mucosa following IR injury., Materials and Methods: Sham (n = 7) and control animals (n = 7) received 48 h of intravenous saline while treatment animals (n = 7) received IL-11 (750 microg/kg/day). Sham animals then underwent laparotomy alone, while control and treatment animals underwent 35 min of mesenteric artery occlusion and 120 min of reperfusion. Midjejunum samples were obtained and serum was drawn. Fluorometric assays were performed for hexosaminidase A (HEX A) and beta-glucuronidase (GLUC), markers of enterocyte necrosis. Apoptosis was quantified by TUNEL and confirmed by DNA fragmentation. Transcription of Bcl-2, an antiapoptotic regulator, was assessed by multiplex RT-PCR. Statistical analysis was performed using ANOVA and expressed as means +/- SEM., Results: In pretreated animals, HEX A and GLUC activities after IR were reduced from 570 +/- 54 to 426 +/- 47 nmol/ml/h (P < 0.05) and from 183 +/- 29 to 125 +/- 7 nmol/ml/h (P < 0.01), respectively. Pretreated animals had a reduced number of apoptotic cells per 10 crypts (79 +/- 11) compared with untreated rats (255 +/- 17) after IR injury (P < 0.01). Mucosal DNA from pretreated rats qualitatively showed less fragmentation on electrophoresis. Relative Bcl-2 band intensity was higher in pretreated animals (1.04 +/- 0.09) compared with controls (0.78 +/- 0.07) (P < 0.05)., Conclusions: IL-11 pretreatment reduced crypt cell apoptosis after IR injury, possibly by upregulating Bcl-2. Treated animals also demonstrated attenuation in the release of certain lysosomal enzymes. These data indicate that following IR injury, IL-11 improves enterocyte survival by reducing necrosis and apoptosis.

Background/purpose: Intestinal ischemia-reperfusion (IR) injury produces necrosis and apoptosis resulting in tissue loss. The authors have observed previously that pretreatment with hepatocyte growth factor (HGF) attenuates enterocyte apoptosis after IR. This study investigated the effects of HGF on tissue levels of caspase-8, an apoptosis initiator, and caspase-3, an apoptosis effector, in intestinal mucosa after IR., Methods: Thirty rats underwent placement of jugular venous catheters connected to osmotic pumps; 15 rats received vehicle, and 15 rats received HGF (150 microg/kg/d). After a 48-hour infusion, 5 rats from each group underwent either 35 minutes of superior mesenteric artery occlusion alone, or ischemia followed by 2 or 6 hours of reperfusion. Mucosal protein was analyzed for caspase-8 and caspase-3 activity. DNA fragmentation was used to measure the presence of apoptosis. Statistical significance was determined using analysis of variance., Results: After 6 hours of reperfusion, caspase-3 activity was increased significantly in control animals (P <.05). In HGF-pretreated animals, caspase-8 and caspase-3 activities were significantly reduced at 6 hours compared with control animals (P <.05)., Conclusion: By preventing the activation of enterocyte caspase enzymes, and, thus, reducing apoptosis, HGF may enhance preservation of the intestine after IR injury., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Background/purpose: Short bowel syndrome results from small intestine loss but frequently is associated with survival of the colon. This study was designed to determine if colonic mucosa could be induced to absorb galactose by tranfection of the sodium glucose cotransporter, SGLT-1 into a colonic segment., Methods: Using 10 rats, a 7-cm segment of colon was infused for 1 hour with a solution containing 50 microg/mL of a plasmid with or without an SGLT-1 insert. An 80% small bowel resection was performed, and the segment was interposed into the small bowel. On the third day [14C] galactose absorption was measured. Mucosal RNA was extracted, and relative band intensities were measured using primers for SGLT-1. Statistical analysis was performed using the Student's t test and expressed as mean +/- SEM., Results: Rats transfected with the SGLT-1 plasmid showed a significant increase (194%) in galactose absorption compared with controls. Transfected animals also showed high levels of of SGLT-1 transcription when compared with controls (792% increase)., Conclusions: These data show that in vivo exposure of colon mucosa to a plasmid containing SGLT-1 allows transfer of that gene into enterocytes. Expression of SGLT-1 can create an absorptive segment that may in part alleviate the malabsorption associated with short bowel syndrome., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Background/purpose: Ischemia-reperfusion (IR) injury to the intestine can result in mucosal damage and cellular death. This study was designed to evaluate the protective effects of pretreatment with hepatocyte growth factor (HGF) on intestine after moderate IR injury., Methods: Control animals (n = 7) received 48 hours of intravenous saline, and treatment animals (n = 7) received HGF (150 microg/kg/d). After 35 minutes of mesenteric artery occlusion and 120 minutes of reperfusion, serum and jejunal mucosa samples were obtained. Fluorometric assays were performed for hexosaminidase A (HEX A) and beta-glucuronidase (GLUC), enzyme markers of enterocyte necrosis. Apoptosis was quantified by the TUNEL method. Transcription of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) was assessed by multiplex reverse transcription polymerase chain reaction (RT-PCR) Statistical analysis was performed using the Student's t test., Results: After HGF pretreatment, HEX A and GLUC activities were reduced from 543 +/- 28 to 343 +/- 35 nmole/h/mL (P <.01) and 183 +/- 29 to 119 +/- 22 nmole/h/mL (P <.01), respectively. Pretreated animals had a reduced number of apoptotic cells per 10 crypts (33 +/- 11) compared with untreated rats (225 +/- 24) after IR injury (P <.01). Mean IFN-gamma band intensity was lower in HGF-pretreated animals (0.05 +/- 0.02) compared with controls (0.31 +/- 0.09; P <.05)., Conclusions: Pretreatment with HGF reduces the severe crypt apoptosis and cellular necrosis after IR injury to the intestine. These data suggest that HGF may be beneficial in attenuating IR damage and thus may have significant clinical application., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Background/purpose: Interleukin-11 (IL-11) is a multifunctional cytokine that has been shown to improve small bowel adaptation and enhance cellular recovery after bowel ischemia. This study was designed to examine the effects of systemic IL-11 on small bowel absorptive function in a rat model of intestinal ischemia and reperfusion (IR) injury., Methods: Sprague-Dawley rats underwent placement of a venous catheter connected to an osmotic pump, which delivered its contents over 3 days. Rats were divided into 3 groups: sham operation/systemic saline; 30-minute superior mesenteric artery occlusion/systemic saline; superior mesenteric artery occlusion/systemic IL-11, 750 microgram/kg/d. After the infusion, (14)C-galactose or (14)C-glycine absorption was measured using an in vivo, recirculation technique. Statistical significance was determined using analysis of variance., Results: In control rats, 30 minutes of IR decreased absorption of galactose from 2.62 to 2.02 micromoles/cm(2) (P <.01), and glycine from 2.79 to 1.72 micromoles/cm(2) (P <.01). Rats treated with systemic IL-11 showed improved absorption of galactose of 2.39 micromoles/cm(2) (P <.05), and glycine at 2.21 micromoles/cm(2) (P <.05). Mucosal DNA content was reduced significantly from 7.37 to 5.61 microgram DNA/mg by IR (P <.01). IL-11 treatment did not significantly alter DNA content during this period., Conclusions: These data show that 30 minutes of intestinal IR significantly decreases intestinal absorptive function in this animal model. When compared with untreated control animals, administration of systemic IL-11 significantly increased the absorption of carbohydrate and amino acid in rats recovering from mesenteric IR., (Copyright 2002 by W.B. Saunders Company.)

Purpose: This study was designed to evaluate the potential growth factor effects of systemic administration of leptin on mucosal mass and absorptive function in normal rat intestine., Methods: Twenty male Sprague-Dawley rats underwent placement of a jugular venous catheter connected to a subcutaneous osmotic pump designed to deliver its contents at a constant rate. The rats were divided into 4 groups (n = 5 per group) based on the contents of the osmotic pump: group 1, 0.1% bovine serum albumin; group 2, leptin, 6.25 microgram/kg/d; Group 3, leptin, 18.75 microgram/kg/d; Group 4, leptin, 43.75 microgram/kg/d. After a 14-day infusion, [(14)C] galactose and [(14)C] glycine absorption were determined using a closed, recirculation technique. DNA content was determined from mucosal biopsies. Total RNA was extracted from mucosal samples, reverse transcribed, and amplified via polymerase chain reaction for the following primer pairs: sodium/glucose cotransporter (SGLT-1), fructose transporter (GLUT-5), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, internal standard). Statistical analysis was performed by analysis of variance and expressed as mean plus minus SEM., Results: Systemic administration of increasing doses of leptin enhanced DNA content when compared with the appropriate control (group 2, 1.06 plus minus 0.04 [P <.05]; group 3, 1.1 plus minus 0.05 [P <.01]; and group 4, 1.07 plus minus 0.06 [P <.05]. Leptin enhanced mucosal absorptive function (galactose: group 2, 2.31 plus minus 0.15 [P <.01]; group 3, 2.71 plus minus 0.06 [P <.01]; group 4, 2.19 plus minus 0.28 [P <.05]; glycine: group 2, 2.34 plus minus 0.31 [P <.05]; group 3, 3.32 plus minus 0.14 [P <.01]; group 4, 3.1 plus minus 0.27 [P <.01]) in the normal intestine when compared with the appropriate control animals. Also, leptin enhanced the gene expression of the carbohydrate transporters when compared with the appropriate control rats., Conclusions: These data show that systemic leptin administration enhances mucosal mass and absorptive function in normal rat intestine. Thus, leptin appears to be a growth factor for normal small intestine and may play a role in patients who acquire intestinal dysfunction., (Copyright 2002 by W.B. Saunders Company.)