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Selenium-enriched broccoli decreases intestinal tumorigenesis in multiple intestinal neoplasia mice.

Multiple intestinal neoplasia (Min) mice are a good model for the investigation of the effects of dietary alterations in a genetic model for intestinal cancer. Previous studies have shown that selenium-enriched broccoli is protective against chemically induced colon cancer susceptibility. This study investigated whether selenium-enriched broccoli would be protective against intestinal cancer susceptibility in Min mice. Five-week-old heterozygotic male Min mice were fed an AIN-93-based diet containing either low-selenium broccoli or an equivalent amount of high-selenium broccoli for 10 wk. Mice fed the selenium-enriched broccoli had fewer (P < 0.02) small intestinal (46.4 +/- 3.7 vs. 65.6 +/- 6.1) and large intestinal (0.43 +/- 0.17 vs. 1.93 +/- 0.27) tumors than those fed an equivalent amount of unenriched broccoli. Min mice fed the selenium-enriched broccoli had small but significant (P < 0.0001) increases in plasma and liver selenium concentrations and red blood cell glutathione peroxidase activity. These results extend previous observations that selenium-enriched broccoli is protective against chemically induced mammary and colon cancer in rats.

Animals↗

Garlic inhibits microsomal triglyceride transfer protein gene expression in human liver and intestinal cell lines and in rat intestine.

Epidemiologic studies have suggested that fresh garlic has lipid-lowering activity. Because the microsomal triglyceride transfer protein (MTP) plays a pivotal role in the assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins, we evaluated the effect of garlic on the expression of the MTP gene in vitro in cell lines and in vivo in rats. Fresh garlic extract (FGE) reduced MTP mRNA levels in both the human hepatoma HepG2 and intestinal carcinoma Caco-2 cells in dose-dependent fashion; significant reductions were detected with 3 g/L FGE. Maximal 72 and 59% reductions, respectively, were observed with 6 g/L FGE. To evaluate the in vivo effect of garlic on MTP gene expression, rats were given a single oral dose of fresh garlic homogenate (FGH), with hepatic and intestinal MTP mRNA measured 3 h after dosing. Rats fed FGH had significantly (46% of the control) lower intestinal MTP mRNA levels compared with the control rats, whereas hepatic MTP mRNA levels were not affected. These results suggest a new mechanism for the hypolipidemic effect of fresh garlic. Long-term dietary supplementation of fresh garlic may exert a lipid-lowering effect partly through reducing intestinal MTP gene expression, thus suppressing the assembly and secretion of chylomicrons from intestine to the blood circulation.

Animals↗

Intestinal phase of pancreatic polypeptide release: the effect of segmental perfusion of the small intestine with various secretagogues.

The purpose of this study was to examine the effect of various nutrients perfused selectively into isolated sections of the small intestine on the release of pancreatic polypeptide (PP). Six dogs were prepared with chronic gastric, duodenal, and three permanent intestinal fistulas (one distal to the ligament of Treitz, one in the terminal ileum, and one halfway between). After a 24-h fast, the duodenum was perfused for 45 min (200 ml/h) via the duodenal limb with HCl (30 mM), an amino acid solution (50 mM), or sodium oleate (NaO, 40 mM). In separate studies, the jejunal and ileal segments were isolated by inflating two balloon catheters via the intestinal fistula, and these segments were perfused as described earlier. Plasma PP, cholecystokinin (CCK)-33, and secretin levels were measured. Results of this study showed that the perfusion of all segments of the small intestine with amino acid caused a significant elevation of plasma PP levels. Perfusion of the duodenum and jejunum but not the ileum with a fatty acid resulted in a significant elevation of plasma levels of PP. Perfusion of HCl into any segment did not affect plasma levels of PP. This study shows that PP is released by the presence of nutrients in all segments of the small intestine, and that a PP elevation was always accompanied with a rise in plasma levels of CCK-33.

Animals↗

Lack of utility of intestinal fatty acid binding protein levels in predicting intestinal allograft rejection.

INTRODUCTION: The enterocyte-specific protein, intestinal fatty acid binding protein (I-FABP), is detectable in serum only after intestinal injury. Previous studies in animals suggest that I-FABP might be a useful marker of intestinal allograft rejection. MATERIALS AND METHODS: I-FABP was repetitively measured in nine intestinal transplant recipients and correlated with findings of surveillance endoscopy. RESULTS: Average interval between I-FABP determination and biopsy was 3.4 days (SD=4.2 days). Average number of rejection episodes per patient totalled 1.6+/-1.2. General linear modeling demonstrated no tendency for increases in serum FABP to precede histologic graft rejection (P=0.263). Restriction of the analysis to I-FABP determinations 1 day before or on the day of biopsy failed to affect these results. Minor increases in I-FABP were often associated with histologically normal grafts, whereas rejection often occurred when I-FABP was not detectable. DISCUSSION: Serum I-FABP levels do not predict clinical intestinal allograft rejection.

Adult↗

Laparoscopic intestinal exploration and full-thickness intestinal biopsy in standing horses: a pilot study.

OBJECTIVE: To assess a laparoscopic technique for equine intestinal biopsy. STUDY DESIGN: Experimental study. ANIMALS: Seven adult horses. METHODS: Food but not water was withheld for 36 hours before laparoscopy. In 3 horses (group A) standing, right laparoscopic access to different small intestinal segments was compared with ventral median celiotomy access. Inaccessible segments were identified at necropsy. In 4 horses (group B), the feasibility of obtaining full-thickness duodenal and cecal biopsies and any associated morbidity were evaluated. Biopsy specimens were collected during standing right laparoscopy using a 2-step procedure and intracorporeal suturing technique, and abdominal lavage was performed. Horses were monitored clinically and by abdominal fluid cytology and microbial culture, and repeat laparoscopy was performed on day 6. RESULTS: Standing right flank laparoscopy provided good observation of small intestinal segments and enabled manipulation of all but 15-20 cm of the duodenum and approximately 40 cm more ileum compared with ventral median celiotomy. Group B horses had no complications, no adhesions, and no bacterial growth from peritoneal fluid samples. None of the horses had signs of abdominal pain. CONCLUSION: A 2-stage intestinal biopsy technique performed during standing, right flank laparoscopy may be a safe alternative to exploratory celiotomy and biopsy in normal horses. CLINICAL RELEVANCE: Right flank laparoscopy allows biopsy of intestinal segments including duodenum and 50% more of the ileum than is accessible by ventral median celiotomy. This technique should be evaluated in clinical patients.

Animals↗

"Small intestinal type" and "colonic type" intestinal metaplasia of the human stomach, and their relationship to the histogenetic types of gastric adenocarcinoma.

Intestinal metaplasia in the non-tumour bearing parts of the gastric mucosa was demonstrated in 24 cases in a material consisting of 27 consecutive patients operated for carcinoma of the stomach. Two mucin histochemical types of intestinal metaplasia could be identified. 1) "Small intestinal type" which was present in all 24 cases, and which was by far the most dominating type. 2) "Colonic type" which occurred in small foci in the gastric mucosa of 11 cases, and which was significantly more frequent in stomachs bearing tumours of presumed intestinal histogenesis, than in those bearing tumours of presumed non-intestinal histogenesis.

Adenocarcinoma↗

Chronic idiopathic intestinal pseudo-obstruction: clinical and intestinal manometric findings.

We report the clinical and intestinal manometric findings in a group of 42 patients with chronic idiopathic intestinal pseudo-obstruction evaluated at the Mayo Clinic. The main clinical manifestations in these patients were nausea and vomiting (83%), abdominal pain (74%), distension (57%), constipation (36%), diarrhoea (29%), and urinary symptoms (17%). These symptoms preceded surgery in all patients. Air fluid levels or distended bowel loops occurred in 57% and a dilated bladder or urinary excretory pathway in 17%. All patients showed intestinal manometric abnormalities none of which are seen in healthy individuals: aberrant configuration or propagation of interdigestive motor complexes in 25 patients; bursts (greater than 2 min duration) of non-propagated phasic pressure activity in fasting and/or fed state in 30 patients; sustained incoordinated fasting pressure activity in 15 patients; and inability of an ingested meal to convert fasting into fed pattern in 28 patients. We conclude that qualitative analysis of intestinal manometry provides evidence of gut dysmotility in patients with the clinical syndrome of chronic intestinal pseudo-obstruction. These abnormalities of motility can help to establish the correct diagnosis.

Adolescent↗

Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea.

Intestinal function is poorly defined in patients with HIV infection. Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting, intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with body mass index. Increased intestinal permeability was found in all subgroups of patients. The changes in absorption-permeability were of comparable severity to those found in patients with untreated coeliac disease. Jejunal histology, however, showed only mild changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes.

Adult↗

Effects of dextran sulphate sodium on intestinal epithelial cells and intestinal lymphocytes.

BACKGROUND AND AIMS: The effects of dextran sulphate sodium (DSS) on mouse intestinal epithelial cells and intraepithelial lymphocytes were analysed to investigate the mechanism by which DSS induces colitis and tumours in mice. Cytotoxicity of DSS towards intestinal epithelial cells and intestinal intraepithelial lymphocyte hybridomas or fresh intestinal intraepithelial lymphocytes seems to have concentration, time, and cell type dependency with increasing concentrations and time causing increased cytotoxicity. RESULTS: Integrin alpha 4 expression was marginally down regulated by 0.5% of DSS, while alpha M290 expression was up regulated. DSS inhibits the binding of 9.1 gamma delta cells to both extracellular matrix (ECM) and epithelial cells. Conversely at high concentrations it increases binding to all ECM except poly-L-lysine. Various cytokines including TGF beta, interleukin 2, and tumour necrosis factor alpha as well as prostaglandin alter the expression of the integrin alpha 4 and M290 subunits at the cell surface, and also alter the adhesion of 9.1 gamma delta cells to epithelial monolayers. The expression of a large number of cell adhesion molecules expressed on intraepithelial lymphocytes is affected by a combination of the abundant gut cytokine TGF beta and DSS, suggesting that DSS induced colitis may ultimately arise from a combination of gut cytokine and DSS. DSS also triggers intraepithelial lymphocyte aggregation on all ECM coated plate tested. CONCLUSIONS: These data suggest that the potential roles of DSS induced colitis may be: (a) direct cytotoxicity; (b) interference with the normal interaction between intestinal lymphocytes, epithelial cells, and ECMs; (c) aberrant modulation of the expression of the integrin beta 7 receptors, other cell receptors, and their functions.

Animals↗

Infantile chronic idiopathic intestinal pseudo-obstruction: the role of small intestinal manometry as a diagnostic tool and prognostic indicator.

BACKGROUND: Chronic idiopathic intestinal pseudo-obstruction (CIIP) presenting in infancy is a rare but serious condition of heterogeneous aetiology often with an uncertain outcome. AIM: To assess whether intestinal manometry in the first two years of life can help define a neuropathic or myopathic aetiology or clinical outcome, or both, in cases of infantile CIIP. SUBJECTS AND METHODS: 14 consecutive children who presented in the first year of life with CIIP were studied histologically and by small intestinal manometry. RESULTS: Five had a myopathic disorder, four were neuropathic, and five unclassified following histological investigation of full thickness intestinal biopsy specimens. Analysis of fasting phase III activity showed four patterns: (1) (n = 4) no detectable motor activity, (2) (n = 5) low amplitude phase III activity, (3) (n = 3) poorly formed phase III complexes of short duration, (4) (n = 2) well formed cyclical phase III activity with abnormal propagation. The seven children with low amplitude phase III: motility index (MI) < 10 KPa/min, all had a poor outcome (death or dependence on parenteral nutrition) after 1-10 years follow up, compared with two of seven of those with a MI > 10 KPa/min. Of the five with myopathic histology, four had a MI < 10 KPa/min. CONCLUSION: These results show that small intestinal manometry is useful not only as an aid in diagnosing the aetiology of CIIP presenting in infancy, but also in predicting outcome.

Chronic Disease↗

ICC pacing mechanisms in intact mouse intestine differ from those in cultured or dissected intestine.

Pacing of mouse intestine is driven by spontaneous activity of a network of interstitial cells of Cajal in the myenteric plexus (ICC-MP). So far, highly dissected circular muscle (CM) strips from control and mutant mice lacking ICC-MP and isolated, cultured ICC from newborn control mice were used to analyze its properties. Using intact circular and longitudinal segments of intestine, we recently reported that there were both significant similarities and differences between pacing studied in segments and from isolated, dissected tissues. Here, we report additional similarities and differences in our model from those in highly reduced systems. Similar to cultured or dissected intestine, blockade of sarcoplasmic-endoplasmic reticulum Ca(2+) pumps with thapsigargin or cyclopiazonic acid reduced pacing frequency, but thapsigargin was less effective than in isolated, cultured ICC. Moreover, inhibition of inositol 1,4,5-trisphosphate (IP(3)) receptors with xestospongin C, a putative inhibitor of IP(3) receptors, failed to affect pacing but successfully blocked increased pacing frequency by phorbol ester. 2-Aminoethoxy-diphenylborate, a putative blocker of IP(3)-mediated calcium release, caused a significant decrease in the amplitude and frequency of contractions. The mitochondrial uncoupler carbonyl cyanide p-trifluormethoxyphenylhydrazone blocked pacing and KCl-induced contractions at a concentration of 1 microM. The cyclic nucleotide agonists sodium nitroprusside (SNP), forskolin, and 8-bromo-cGMP inhibited pacing in CM. In longitudinal muscle (LM), SNP and forskolin had little effect on pacing. Furthermore, dibutyryl-cAMP did not affect pacing in CM or LM. These results suggest that pacing in intact intestine is under partly similar regulatory control as in more reduced systems. However, pacing in intact intestine is not affected by xestospongin C, which abolishes pacing in isolated, cultured ICC and exhibits attenuated responses to thapsigargin. Also, major differences between LM and CM suggest a separate pacemaker may drive LM.

Anesthetics, Local↗

Role of gut flora on intestinal group II phospholipase A2 activity and intestinal injury in shock.

We previously showed that group II phospholipase A2 (PLA2-II), a secretory, bactericidal, and proinflammatory protein in intestinal crypts, is upregulated after lipopolysaccharide (LPS) and platelet-activating factor (PAF) challenge. Here we examined whether germ-free environment (GF) or antibiotic treatment (ABX) affects the pathophysiological responses and intestinal PLA2-II activity after PAF (1.5 microg/kg) or LPS (8 mg/kg) injection. We found that LPS and PAF induced hypotension and mild intestinal injury in conventionally fed (CN) rats; these changes were milder in ABX rats, whereas GF rats showed no intestinal injury. PLA2-II enzyme activity was detected in normal rat small intestine; the basal level was not diminished in ABX or GF rats. PAF and LPS caused an increase in PLA2-II activity, which was abrogated in GF and ABX rats. Recolonization of GF rats by enteral contamination restituted their PLA2-II response to PAF and LPS and susceptibility to bowel injury. We conclude that PAF- and LPS-induced increases in PLA2-II activity are dependent on gut bacteria, and ABX and GF rats are less susceptible to LPS-induced injury than CN rats.

Animals↗

Neutrophil migration across the intestinal epithelial barrier--summary of in vitro data and description of a new transgenic mouse model with doxycycline-inducible interleukin-8 expression in intestinal epithelial cells.

The intestinal epithelium serves as a protective barrier between the gut lumen and the underlying mucosa. During intestinal inflammation in inflammatory bowel disease (IBD) there is increased paracellular permeability and strong migration of the neutrophils into the mucosa as well as transepithelial neutrophil migration with the formation of crypt abscesses. From in vitro data we know that neutrophil migration is triggered by epithelial-derived interleukin-8 (IL-8). A pathogen-elicited epithelial chemoattractant activity, which is released by intestinal epithelial cells from the apical surface, seems to be responsible for the final step in transepithelial migration. To mimic the pathophysiological situation with influx of neutrophils during IBD, a double transgenic mouse model with doxycycline-inducible IL-8 expression in intestinal epithelial cells was established. This model will allow to study the role of neutrophil influx during chronic intestinal inflammation. It will also provide insights into the mechanisms of neutrophil transepithelial migration.

Animals↗

Patients with chronic renal failure have abnormal small intestinal motility and a high prevalence of small intestinal bacterial overgrowth.

BACKGROUND/AIMS: Gastrointestinal (GI) symptoms are common among patients with chronic renal failure (CRF). The pathogenesis of these symptoms is probably multifactorial. Our aims were to assess gastric and small intestinal motility and the prevalence of small intestinal bacterial overgrowth (SIBO) in order to clarify possible pathophysiological mechanisms behind these symptoms in CRF patients. METHODS: Twenty-two patients with CRF, 12 with GI symptoms and 10 without GI symptoms underwent antroduodenojejunal manometry. All patients with GI symptoms had diarrhea and half of them had abdominal pain, nausea and/or early satiety. Symptoms were unexplained by conventional investigations. Interdigestive motility was recorded for 5 h and postprandially for 1 h. Samples for culture from the small intestine were obtained through the manometry catheter. Results were compared with 34 healthy controls. RESULTS: On manometry, 11 CRF patients demonstrated neuropathic-like abnormalities, with no significant difference between the patients with (7/12) and without (4/10) GI symptoms. SIBO was seen in 8 CRF patients (36%), 3 with and 5 without GI symptoms (p = 0.15). Six of eleven (55%) of the CRF patients with neuropathic-like abnormalities had SIBO, compared to 2/11 (18%) in those without abnormalities on conventional analysis (p = 0.07). The propagation velocity of phase III was significantly faster in CRF patients with GI symptoms compared to CRF patients without symptoms and healthy controls (21.4 (16.4-54.7) vs. 8.1 (4.6-9.6) and 10.8 (7.2-21.6) cm/min, p = 0.007 and p = 0.019, respectively). We found a higher proportion of retrograde pressure waves in late phase II in the proximal duodenum in patients with and without GI symptoms, than in healthy controls (29 (17-38) and 16 (14-42) vs. 8 (0-24)%, p < 0.0001 and p = 0.0005, respectively). The number of long clusters during the fasting recording was higher in both patient groups than in controls (9 (5-21) and 11 (7-15) vs. 4 (2-9)/5, p = 0.046 and p = 0.002, respectively). CONCLUSION: In the small intestine, abnormal motility and bacterial overgrowth are common in patients with chronic renal failure. These alterations correlate poorly with GI symptoms, but disturbed intestinal motility might explain diarrhea in some of these patients.

Adult↗

Effects of fish meal as source of protein on intestinal maltase activity and intestinal and renal leucine aminopeptidase activity of growing rats.

The effect of high-protein fish meal on maltase and leucine aminopeptidase (LAPase) activities of the intestinal mucosa as well as the renal LAPase activity was studied. Four groups of female Wistar rats, weighing between 40-60 g, were fed diets with a 4 or 12% protein content of dry matter for 25 days. The protein source was casein for the control groups and fish meal derived from Coryphaenoides rupestris for the test groups. The results show a decrease (p less than 0.005) in intestinal maltase and LAPase activities and renal LAPase activity in animals fed with 12% of fish meal protein compared to those fed with casein, while the rats fed 4% of fish meal protein showed a decrease in intestinal maltase activity and no significant difference in LAPase activity compared with the control group. These results seem to indicate that the intestinal maltase is influenced by the quality and quantity of dietary protein, while the intestinal and renal LAPase activity is only changed by the quality of protein.

Animals↗

Intestinal non-Hodgkin's lymphoma: a multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin's Lymphoma.

PURPOSE: Intestinal non-Hodgkin's lymphomas are not well characterized. We therefore studied prospectively their clinical features and response to standardized therapy. PATIENTS AND METHODS: Fifty-six patients with primary intestinal lymphoma were included in a prospective, nonrandomized multicenter study. Lymphoma resection was recommended and staging was performed according to the Ann Arbor classification. Patients were scheduled to receive six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy, and at stages EIII to EIV, they received additional involved-field radiotherapy. Corticosteroids were used in patients who could not receive chemotherapy. RESULTS: Thirty-five patients had intestinal T-cell lymphoma (ITCL), 21 patients had intestinal B-cell lymphoma (IBCL; 18 diffuse large-cell lymphomas, two marginal-cell lymphomas, and one follicle-center lymphoma). Thirty-four patients at stages EI to EII (14 ITCL and 20 IBCL) and nine patients at stages EIII to EIV (all ITCL) received chemotherapy. No patient in stages EIII to EIV received radiotherapy, because death occurred in 12 of 14 patients. Two-year cumulative survival in patients with IBCL was 94% (95% CI, 82% to 100%) and higher than in patients with ITCL (28% [95% CI, 13% to 43%]; P <.0001), even when only stages EI to EII were considered (ITCL, 37.5% [95% CI, 16.5% to 58.5%]; P <.0001). IBCL patients compared with ITCL patients were at lower lymphoma stages (P <.01), had higher Karnofsky status (P <.005), had intestinal perforation less often (P <.05), required emergency operation less often (P <.05), received CHOP (P <.05) more often, and reached complete remission (P <.0005) more frequently. CONCLUSION: IBCL patients at stages EI and EII respond well to chemotherapy, but the prognosis and treatment of ITCL patients is unsatisfactory.

Adult↗

Prevention by mannan and other sugars of in vitro damage of rat fetal small intestine induced by cereal prolamin peptides toxic for human celiac intestine.

Peptic-tryptic-cotazym and peptic-tryptic digests were obtained, simulating in vivo protein digestion, from pure "bread" wheat gliadins and from rye, barley, and oats prolamine and tested on small intestine cultures from fetal rats. When tested at a concentration of 0.1 mg of peptides/ml of culture medium the peptic-tryptic-cotazym and peptic-tryptic digests of gliadin and prolamines were very active in slowing in vitro development of fetal rat intestine and in increasing the occurrence and severity of degenerative changes. The ability of some sugars to interfere with inhibition of fetal intestinal morphogenesis induced by these peptides was also tested. Mannan at a concentration of 0.1 mM was effective in allowing intestinal morphogenesis to take place in the presence of prolamine peptic-tryptic-cotazym and prolamine peptic-tryptic digests of the four toxic cereals. Some oligomers of N-acetyl-glucosamine were also effective in blocking the inhibitory effect of "bread" wheat gliadin peptides. These data are compatible with the hypothesis that some sugars may exert a protective effect on the toxic activity of cereal prolamin peptides on the human celiac intestine.

Animals↗

Patent ductus arteriosus, indomethacin, and intestinal distension: effects on intestinal blood flow and oxygen consumption.

To determine the relative importance of patent ductus arteriosus, indomethacin, and intestinal distension as factors that promote terminal ileum ischemia, eight near-term fetal lambs were surgically prepared by in situ cannulation of the proximal and distal ends of a loop of terminal ileum, formalin infiltration of the ductus arteriosus, and placement of a snare around the ductus arteriosus to control its patency. The incisions were closed; the lambs were delivered and mechanically ventilated. Terminal ileum blood flow and oxygen consumption were measured after the loop of ileum had been distended with 0.9% NaCl to luminal pressures of 1-2, 7, and 18 mm Hg (0.13-0.26, 0.93, and 2.38 kPa) (pressures observed in the intestinal lumen after feeding and during pathologic conditions). The effect of these pressures on terminal ileum blood flow and oxygen consumption was examined: 1) with ductus closed, 2) with ductus open, and 3) 1 h after administration of indomethacin (0.3 mg/kg; 0.8 mumol/kg) with ductus closed. Both open ductus and indomethacin produced a significant decrease in intestinal blood flow. This occurred over the entire range of luminal pressures examined. In all three study conditions, terminal ileum blood flow fell commensurate with a fall in perfusion pressure. Despite this absence of pressure-flow autoregulation, oxygen consumption was maintained when the ductus was closed or open. In contrast, indomethacin inhibited the ability of the terminal ileum to autoregulate its oxygen consumption. These findings suggest that both open ductus and indomethacin present an increased risk of intestinal ischemia. We hypothesize that indomethacin's beneficial effect on ductus closure may be counterbalanced by its negative effect on intestinal perfusion and metabolism.

Animals↗