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PubMed2002

Heparin-binding EGF-like growth factor preserves crypt cell proliferation and decreases bacterial translocation after intestinal ischemia/reperfusion injury.

BACKGROUND/PURPOSE: Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), a known mitogenic, chemotactic, and cytoprotective growth factor for epithelial cells, was examined to see whether it could protect intestinal barrier function and decrease bacterial translocation (BT) after ischemia/reperfusion (I/R) injury. METHODS: In vitro, tight junctional integrity of intestinal epithelial cells (IEC-6) cells was evaluated by measuring transepithelial electric resistance (TEER), and monolayer permeability was evaluated by translocation of Escherichia coli C25. In vivo, crypt cell proliferation was assessed by 5-bromodeoxyuridine incorporation with calculation of a proliferative index (PI), and BT was evaluated by culture of mesenteric lymph nodes. RESULTS: In vitro, anoxia damaged tight junctional integrity and increased permeability of IEC-6 cell monolayers, events that were reversed completely by treatment of the cells with HB-EGF. Twenty-four hours after I/R injury in vivo, crypt cell proliferation index (PI) decreased significantly from 35.6 +/- 4.5 to 17.8 +/- 3.4. Administration of HB-EGF preserved crypt cell activity with PI of 34.9 +/- 4.1, similar to that of normal ileum. None of the normal or sham-operated animals showed BT, whereas BT occurred in 87.5% of I/R-injured rats. In animals exposed to I/R but treated with HB-EGF, BT was decreased significantly to 12.5%. CONCLUSION: HB-EGF preserves proliferation of crypt cells, maintains integrity of epithelial cells, and subsequently decreases enteric BT after I/R injury.

Animals↗
PubMed2003

Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis.

Intestinal barrier failure and subsequent bacterial translocation have been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis. Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as a cause of increased intestinal permeability. The urinary concentration of intestinal fatty acid binding protein (IFABP) has been shown to be a sensitive marker of intestinal ischemia, with increased levels being associated with ischemia/reperfusion. The aim of the current study was to assess the relationship between excretion of IFABP in urine, gut mucosal barrier failure (intestinal hyperpermeability and systemic exposure to endotoxemia), and clinical severity. Patients with a clinical and biochemical diagnosis of acute pancreatitis were studied within 72 hours of onset of pain. Polyethylene glycol probes of 3350 kDa and 400 kDa were administered enterally, and the ratio of the percentage of retrieval of each probe after renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine the IFABP concentration (IFABP-c) and total IFABP (IFABP-t) excreted over the 24-hour period, using an enzyme-linked immunosorbent assay technique. The systemic inflammatory response was estimated from peak 0 to 72-hour plasma C-reactive protein levels, and systemic exposure to endotoxins was measured using serum IgM endotoxin cytoplasmic antibody (EndoCAb) levels. The severity of the attack was assessed on the basis of the Atlanta criteria. Sixty-one patients with acute pancreatitis (severe in 19) and 12 healthy control subjects were studied. Compared to mild attacks, severe attacks were associated with significantly higher urinary IFABP-c (median 1092 pg/ml vs. 84 pg/ml; P < 0.001) and IFABP-t (median 1.14 microg vs. 0.21 microg; P = 0.003). Furthermore, the control group had significantly lower IFABP-c (median 37 pg/ml; P = 0.029) and IFABP-t (median 0.06 microg; P = 0.005) than patients with mild attacks. IFABP correlated positively with the polyethylene glycol 3350 percentage retrieval (r = 0.50; P < 0.001), CRP (r = 0.51; P < 0.001), and inversely with serum IgM EndoCAb levels (r = -0.32; P = 0.02). The results of this study support the hypothesis that splanchnic hypoperfusion contributes to the loss of intestinal mucosal integrity associated with a severe attack of pancreatitis.

Acute Disease↗
PubMed1994

The effect of dexamethasone administration on rat intestinal permeability: the role of bacterial adherence.

BACKGROUND/AIMS: Previous studies have shown that dexamethasone administration to rats results in diminution of biliary secretory immunoglobulin A concentration and alters intestinal barrier function to bacteria. The aims of this study were to examine and characterize the effect of dexamethasone on intestinal permeability and to determine the possible influence of bacterial adherence to the mucosa in this process. METHODS: Groups of adult Fisher rats were studied, and the effects of dexamethasone administration and bowel decontamination on bacterial adherence and intestinal permeability were determined in various bowel segments. RESULTS: Dexamethasone administration was associated with a significant increase in bacterial adherence to the mucosa, which was most pronounced in the cecum (4.33 +/- 0.2 colony forming units (cfu) (log10) per gram of mucosa for control vs. 6.23 +/- 0.2 for dexamethasone). This was accompanied by significant alterations in intestinal permeability as measured by a decrease in transepithelial electrical resistance (49.5 +/- 4.1 omega.cm2 for control vs. 25.4 +/- 2.5 omega.cm2 for dexamethasone). Dual sodium-mannitol flux analysis showed this defect to be predominantly paracellular. Antibiotic decontamination of the intestine completely abrogated the intestinal permeability defect observed in this model. CONCLUSIONS: Bacterial-mucosal cell interactions may be responsible for alterations in intestinal permeability after dexamethasone administration.

Animals↗
PubMed2007

Review article: glucagon-like peptide 2--current applications and future directions.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is an important peptide growth factor secreted from the human intestine. The trophic properties of GLP-2 are very specific to the gut where it is pivotal in the regulation of mucosal morphology, function and integrity. AIMS: This review details the current understanding of the molecular biology of GLP-2, its mechanisms of action and physiological properties. A major focus is the discussion of recent clinical data evaluating the use of GLP-2 as a therapeutic agent. METHODS: Relevant articles were identified using Medline searches and from the reference lists of key papers. RESULTS AND CONCLUSIONS: In the treatment of short bowel syndrome, GLP-2 has been shown to be highly effective in improving fluid absorption. In Crohn's disease, GLP-2 is superior to placebo in the induction of remission. Early data also suggest that the effects of GLP-2 on bone metabolism can provide a new treatment approach for patients with osteoporosis. In the future, the positive effects of GLP-2 on intestinal barrier function, splanchnic perfusion and mucosal healing could be utilized to expand its therapeutic application to other causes of intestinal injury. However, important safety aspects need to be considered when using this potent growth-promoting agent for a long term.

Amino Acid Sequence↗
PubMedDate not supplied

Harry M. Vars award. Glutamine or fiber supplementation of a defined formula diet: impact on bacterial translocation, tissue composition, and response to endotoxin.

Despite provision of adequate calories, defined formula diets in rats lead to bacterial translocation (BT), fatty infiltration of the liver, and an increased susceptibility to endotoxin. These deleterious effects may be due in part to a loss of intestinal barrier integrity resulting from bowel atrophy. Defined formula diets lack both glutamine and fiber, substances which may help maintain intestinal mass. To determine whether supplementation of defined formula diets with either glutamine or fiber might prevent bowel atrophy and, thus, BT, hepatic steatosis, and the altered response to endotoxin, Wistar rats were fed (1) defined formula diet ad libitum (DFD), (2) (DFD + 2% (w/v) glutamine, (GLUT), or (3) DFD + 2% (w/v) psyllium (FIBER). Rats given standard food isocalorically pair-fed to DFD were used as controls. Nutritional status was assessed by daily weight gain, as well as the ability to maintain serum albumin, hematocrit and white blood counts. After 2 weeks of these feeding regimens, animals were sacrificed, and organ weights and composition were determined, with rates of bacterial translocation determined by mesenteric lymph node, abdominal viscera, and cecal cultures. Additional animals receiving the same experimental diets were subsequently challenged with endotoxin and observed for mortality with rates of post-endotoxin BT and the responses of acute phase proteins and cytokines measured. All dietary regimens resulted in equivalent weight gain and other nutritional parameters. Both glutamine and fiber supplementation maintained small bowel mass, but only GLUT preserved normal jejunal mucosal architecture. Neither fiber nor glutamine supplementation prevented cecal bacterial overgrowth or BT, resulting from the DFD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Effect of Helicobacter pylori and eradication therapy on gastrointestinal permeability. Implications for patients with seronegative spondyloarthritis.

OBJECTIVE: Disruption of intestinal barrier function, followed by increased antigen load, may possibly trigger joint inflammation. In seronegative spondyloarthritis (SpA) both gut inflammation and altered intestinal permeability have been reported. We evaluated the influence of Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAID) on gastrointestinal (GI) permeability in SpA. Twenty SpA patients (7 women, mean age 47 +/- 13 SD yrs), 30 patients with endoscopic gastritis (EndG; 17 women, mean age 48 +/- 14 yrs), and 35 healthy controls (16 women, mean age 40 +/- 15 yrs) were studied. No patient was undergoing antisecretory therapy. In the SpA group, 8 patients were chronically taking NSAID and 12 took NSAID occasionally, none during the month before the study. All subjects were assessed for gastroduodenal (sucrose) and intestinal (lactulose/mannitol) permeability test and H. pylori status (urea breath test). RESULTS: H. pylori affected GI permeability in both SpA and EndG patients. After eradication therapy, sucrose excretion remained increased in SpA and reverted to normal in EndG patients, whereas lactulose/mannitol test became comparable to controls in both groups. SpA patients taking chronic NSAID had increased gastroduodenal permeability only when H. pylori-positive. In SpA patients, GI permeability did not correlate with clinical activity or biochemical inflammation. CONCLUSION: In SpA, H. pylori and NSAID contribute to impaired GI permeability. Eradication therapy may help to maintain epithelial barrier function and possibly influence clinical improvement in patients with SpA.

Adult↗
PubMed2005

The effect of cytostatic drug treatment on intestine-specific transcription factors Cdx2, GATA-4 and HNF-1alpha in mice.

Chemotherapy-induced intestinal damage is a very important dose-limiting side effect for which there is no definitive prophylaxis or treatment. This is in part due to the lack of understanding of its pathophysiology and impact on intestinal differentiation. The objective of this study was to investigate the gene expression of the small intestinal transcription factors HNF-1alpha, Cdx2, GATA-4 in an experimental model of methotrexate (MTX)-induced intestinal damage, and to correlate these alterations with histological damage, epithelial proliferation and differentiation. HNF-1alpha, Cdx2 and GATA-4 are critical transcription factors in epithelial differentiation, and in combination they act as promoting factors of the sucrase-isomaltase (SI) gene, an enterocyte-specific differentiation marker which is distinctly downregulated after MTX treatment. Mice received two doses of MTX i.v. on two consecutive days and were sacrificed 1, 3 and 7 or 9 days after final injection. Segments of the jejunum were taken for morphological, immunohistochemical and quantitative analyses. Intestinal damage was most severe at day 3 and was associated with decreased expression of the transcriptional factors HNF-1alpha, Cdx2 and GATA-4, which correlated well with decreased expression of SI, and seemed inversely correlated with enhanced proliferation of epithelial crypt cells. During severe damage, the epithelium was preferentially concerned with proliferation rather than differentiation, most likely in order to restore the small intestinal barrier function rather than maintaining its absorptive function. Since HNF-1alpha, Cdx2 and GATA-4 are critical for intestine-specific gene expression and therefore crucial in epithelial differentiation, these results may explain, at least in part, why intestinal differentiation is compromised during MTX treatment.

Animals↗
PubMed1990

Intestinal permeability is increased in burn patients shortly after injury.

There is increasing direct experimental and indirect clinical evidence to indicate that under certain conditions intestinal barrier function may be lost in trauma victims. No direct measurements, however, have been performed in patients to determine whether intestinal permeability is increased shortly after a major thermal injury in the absence of infection. Fifteen hemodynamically stable burn patients with burns on more than 20% of their body surface (39% +/- 12%) had their intestinal permeability measured within 24 hours of injury with use of the two nonmetabolizable sugars lactulose and mannitol as permeability markers. Lactulose absorption was fourfold higher in the patients (223 +/- 54 mumol) than in the controls (58 +/- 11 mumole; p less than 0.02), whereas the lactulose/mannitol ratio was threefold higher (5.2 vs 1.7; p less than 0.05). Thus intestinal permeability was increased in patients with moderate to major burn injuries shortly after injury.

Absorption↗
PubMed1988

[Physiology of food intake and regulation of body weight].

Feeding is often influenced by competitive needs or by environmental factors. Nevertheless, in physiological conditions hunger is elicited by depletion of macronutrients. The first question is what specific signals cause food intake? Recent data suggest that the signal comes not from exclusive depletion of carbohydrates or of anyone type of the major macronutrients but from overall decreased cellular power production (hypoischymetric signal). Locomotion free metabolic rate has been shown to decrease preceding hunger and to increase in order to determine satiety. Satiation, which occurs largely before ingested nutrients can cross the intestinal barrier and replete the inner milieu, obeys a specific mechanism. Following the stimulation by ingestion of the oro-gastro-intestinal receptors metabolic hormones such as glucagon and insulin are released and enhance metabolism of endogenous reserves. The so-induced endogenous "meal" brings about an anticipatory hypermetabolism which inhibits further ingestion. Post-absorptive satiety subsequently will replace the pre-absorptive state of satiation. The long term regulation of body weight is more subtle. When the actual body weight exceeds its defended value, responsiveness towards signals of hunger diminishes. This hyporesponsiveness seems to be a consequent of an enlargement of the microscopic fat depot at the level of hypothalamic receptive structures which parallels the peripheral increase of the macroscopic fat depot. Thus, hunger promoting signals become less effective and feeding decreases. A symmetrical process takes place in case of body weight loss which results in central hyperresponsiveness to hunger related stimuli and thus facilitates feeding and body weight recovery.

Body Weight↗
PubMed1993

Ischemia-reperfusion in feline small intestine: a role for nitric oxide.

The objective of this study was to assess whether nitric oxide synthesis inhibition affects intestinal barrier function after ischemia-reperfusion of the feline small bowel. Local intra-arterial infusion of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol.ml-1.min-1) was performed in autoperfused segments of cat ileum for 60 min after 90 min of ischemia and 60 min of reperfusion. Epithelial permeability was quantitated by measuring blood-to-lumen clearance of 51Cr-labeled EDTA, and microvascular dysfunction was assessed by measuring the clearance of protein from the vasculature into the interstitium. 125I-labeled albumin clearance from blood to lumen and histology were performed to further characterize the extent of intestinal dysfunction after reperfusion of the postischemic intestine in the presence and absence of L-NAME. Ischemia-reperfusion-induced mucosal and microvascular permeability increases were dramatically augmented by L-NAME infusion, and this effect was reversed by infusion of L-arginine (125 nmol.ml-1.min-1). Initiating L-arginine (but not D-arginine) infusion alone 10 min before reperfusion provided protection against ischemia-reperfusion-induced mucosal barrier dysfunction; however, this was not associated with a reduction in endogenous levels of L-arginine during ischemia-reperfusion. These data suggest that basal nitric oxide production is important in minimizing mucosal and microvascular barrier dysfunction associated with reperfusion of postischemic intestine.

Animals↗
PubMed1997

Prostaglandins I2 and E2 have a synergistic role in rescuing epithelial barrier function in porcine ileum.

Prostaglandins (PG) are cytoprotective for gastrointestinal epithelium, possibly because they enhance mucosal repair. The objective of the present studies was to assess the role of prostaglandins in intestinal repair. Intestinal mucosa from porcine ileum subjected to 1 h of ischemia was mounted in Ussing chambers. Recovery of normal transepithelial electrical resistance occurred within 2 h, and continued to increase for a further 2 h to a value twice that of control. The latter response was blocked by inhibition of prostaglandin synthesis, and restored by addition of both carbacyclin (an analog of PGI2) and PGE2, whereas the addition of each alone had little effect. Histologically, prostaglandins had no effect on epithelial restitution or villous contraction, indicating that elevations in transepithelial resistance were associated with increases in paracellular resistance. Furthermore, prostaglandin-stimulated elevations in resistance were inhibited with cytochalasin D, an agent known to stimulate cytoskeletal contraction. Synergistic elevations in transepithelial resistance, similar to those of carbacyclin and PGE2, were also noted after treatment with cAMP and A23187 (a calcium ionophore). We conclude that PGE2 and PGI2 have a synergistic role in restoration of intestinal barrier function by increasing intracellular cAMP and Ca2+, respectively, which in turn signal cytoskeletal-mediated tight junction closure.

Animals↗
PubMed2002

Elemental and intravenous total parenteral nutrition diet-induced gut barrier failure is intestinal site specific and can be prevented by feeding nonfermentable fiber.

OBJECTIVE: Parenteral nutrition and elemental diets both cause bacterial translocation, immune dysfunction, and increased infection in laboratory animals, whereas elemental diets, with or without fiber, ameliorate some, but not all gut barrier failure. The purpose of this study is to investigate, in an Ussing chamber system, whether elemental vs. parenteral diets induce gut barrier failure in specific anatomical sites in the intestine and whether fiber can ameliorate this phenomenon. DESIGN: Controlled study in laboratory animals. SETTING: University laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Nutritional support was provided to rats for 7 days by oral total parenteral nutrition (TPN; elemental diet) 307 kcal/kg/day, intravenous TPN (parenteral diet) 307 kcal/kg/day via jugular venous catheters, or rodent chow (controls). MEASUREMENTS AND MAIN RESULTS: Permeability to bacteria in intestinal segments of ileum, jejunum, and colon was evaluated in an Ussing chamber. Results were correlated with bacterial translocation to the mesenteric lymph nodes. Intravenous TPN caused greater bacterial translocation in all small intestinal segments and the cecum when compared with chow (p <.05). Oral TPN caused gut barrier failure only in the ileal segment, but not in the remainder of the small intestine (p <.001). Addition of cellulose provided a greater protection of the ileum to permeability than did pectin (p <.01). CONCLUSIONS: TPN causes global intestinal barrier failure, but elemental diet prevents barrier failure in parts of the small intestine other than the ileum. The addition of cellulose fiber to elemental diet can ameliorate further barrier failure in the ileum.

Analysis of Variance↗
PubMed1998

Interactions of the bacterial pathogen Listeria monocytogenes with mammalian cells: bacterial factors, cellular ligands, and signaling.

Listeria monocytogenes is a food borne pathogen which has the very unique property of crossing three barriers during infection eliciting meningitis, meningo-encephalitis and abortions with a mortality rate of about 30%. Indeed, after crossing the intestinal barrier, Listeria disseminates via the lymph and the blood, to the brain and/or the placenta after crossing the brain-blood barrier and/or the placental barrier. During disease, this organism infects a variety of tissues and cell types in which it is mostly intracellular due to its capacity to induce its own phagocytosis into cells which are normally nonphagocytic. The strategies used by Listeria to enter cells are different from those used by other well known invasive pathogens. Listeria thus appears as a fine model to study the molecular and cellular basis of bacterial invasion. In addition, not only during entry into cells but also during intra- and intercellular movement, Listeria exploits mammalian cell functions and is thus a novel tool for elucidating some unsolved fundamental aspects of cell biology, such as ligand receptor signaling and actin cytoskeleton rearrangements. In this review, the molecular and cellular basis of entry of Listeria into cells and of its intracellular motility will be discussed.

Animals↗
PubMed1989

Mechanisms of polyethylene glycol 400 permeability of perfused rat intestine.

Abnormal permeability to polyethylene glycol 400 (PEG 400) has been demonstrated in various disorders with defective intestinal barrier functions. To understand the basic mechanisms of PEG 400 permeability, we compared PEG 400 permeation in different segments of the intestine and studied the kinetics and influence of intraluminal factors on PEG 400 absorption in vivo in perfused intestinal segments of the rat. The permeation rate of PEG 400 was dependent on the luminal concentration (y = 12.99x + 3.5; r = 0.97), indicating that passive movement is the mechanism involved in PEG 400 absorption. Changing the perfusate pH from 6 to 7.4 or modifying the unstirred water layer resistance by changing luminal flow rate did not affect PEG 400 absorption. When luminal osmolarity was varied from 0.225 to 0.6 osmol/L, higher osmolarity decreased both water and PEG 400 absorption (p greater than 0.01). The relationship between PEG 400 and water absorption at different osmolarities was linear (y = 0.9x + 5.7; r = 0.98). At a luminal osmolarity of 0.3 osmol/L 43% of PEG 400 permeation was mediated by passive diffusion and 57% was mediated by solvent drag. Increasing water absorption by decreasing luminal osmolarity resulted in proportional increase of PEG 400 permeation through solvent drag or convection. The solvent drag reflection coefficient (sigma f) for PEG 400 permeation of the jejunum was 0.1. Taurocholic acid (10 mM) alone or with oleic acid (2.5 mM) did not affect PEG 400 absorption. Permeabilities of 1 mM PEG 400 and water were similar in jejunum and ileum but were markedly increased in the colon (p greater than 0.01). These studies demonstrate that PEG 400 is absorbed by both passive diffusion and by solvent drag, with the latter accounting for a greater fraction of the absorptive drive under normal conditions. Polyethylene glycol 400 uses aqueous pathways for its permeation across the intestinal epithelium.

Animals↗
PubMed2006

Antidepressants attenuate increased susceptibility to colitis in a murine model of depression.

BACKGROUND & AIMS: Psychiatric factors may determine gastrointestinal health outcomes. Here, we used a model of depression based on neonatal maternal separation (MS) to identify alterations in gut physiology and to assess its association with increased sensitivity to experimental colitis in adulthood. We also examined whether antidepressant therapy attenuates the increased susceptibility to colitis. METHODS: C57BL/6 mouse pups were separated from mothers for 3 hours per day at 1-21 days of age. Maternally unseparated (US) litters served as controls. At 8 weeks of age mice were examined for changes in behavior, intestinal permeability, and sensitivity to colitis. Separate sets of MS and US mice were given either saline or the antidepressant desipramine 15 mg/kg once daily at 23-36 days of age. Testing of mice occurred at 8 weeks of age. RESULTS: Adult MS mice showed evidence of depressive-like behavior and enhanced intestinal permeability but showed no evidence of spontaneous inflammation. A more severe colitis was seen in MS compared with US mice. Antidepressant therapy improved parameters of depressive-like behavior and reduced the vulnerability to dextran sulphate sodium colitis in MS mice but had no effect on colitis in US mice. CONCLUSIONS: MS may lead to depression and increased responsiveness to stress, to impaired intestinal barrier function, and to enhanced vulnerability to colitis in adulthood. This vulnerability is reversed by antidepressant therapy. Depression increases vulnerability to intestinal inflammation. We speculate that pre-existing depression may facilitate the expression of inflammatory bowel diseases.

Animals↗
PubMed1999

The effect of sennosides on bacterial translocation and survival in a model of acute hemorrhagic pancreatitis.

Bacterial translocation leading to subsequent infectious complications is a significant determinant of outcome in acute hemorrhagic pancreatitis (AHP). The colonic ileus and impaired intestinal barrier function that often accompany AHP may predispose to translocation. Sennoside is a naturally occurring cathartic and choleretic agent that stimulates intestinal mucous secretion and has potent promotility effects. The impact of sennoside-induced intestinal motility and secretory function on bacterial translocation and survival was studied in a rat model of AHP. Severe acute pancreatitis was induced in rats by the intraductal infusion of 2% sodium deoxycholate (DCA, 0.4 ml/kg). A group of sham-operated rats (group A) received intraductal saline, whereas experimental animals were subsequently administered distilled water (group B) or sennoside solution (group C) by gavage every 8 h. After 48 h, intestinal transit of fluorescein isothiocyanate-labeled dextran, serum endotoxin, and amylase levels, and bacterial translocation to mesenteric lymph nodes (MLNs) and pancreatic tissue were determined. The pancreas and intestine were sampled for histologic study. All group A animals survived and did not develop pancreatitis or endotoxemia, whereas groups B and C all demonstrated severe hemorrhagic pancreatitis with evidence of necrosis. Mortality at 48 h was 55% in group B versus 12.5% in group C. Inhibition of intestinal motility was noted in 40% versus 20%, and endotoxin levels were 61.36+/-28.26 pg/L versus 5.41+/-3.58 pg/L in group B versus group C rats, respectively (p<0.001). Pancreatic tissue and MLN cultures were positive in 100% of group B survivors versus 14% of group C survivors (p<0.05). Histologic examination of the intestine in group C animals showed increased mucous secretion, proliferation of goblet cells, and evidence of rapid turnover/renewal of enterocytes. Treatment with the cathartic agent, sennoside, reduced translocation of endotoxin and bacteria, restored intestinal motility, increased mucous secretion, and reduced mortality in a model of acute hemorrhagic pancreatitis in the rat. Other cathartics may have similar properties and may be useful in preventing infectious complications in acute pancreatitis.

Acute Disease↗
PubMed1999

Nitric oxide promotes the internalization and passage of viable bacteria through cultured Caco-2 intestinal epithelial cells.

Nitric oxide (NO) may play an important role in the pathophysiology of intestinal barrier disruption. Our purpose was to investigate the effects of NO donors on the internalization and passage of bacteria through cultured intestinal epithelial cells. Human intestinal epithelial cell line Caco-2 cells were grown on microtiter plastic plates. The cells were incubated with Escherichia coli and sodium nitroprusside (SNP) or S-nitroso-N-acetyl-penicillamine (SNAP), as NO donors, at several concentrations. The numbers of viable bacteria internalized into the epithelial cells were measured. Caco-2 cells were also grown to confluency on membranes of bicameral systems. The cells were incubated with E. coli and SNP. The numbers of viable bacteria passed through the epithelial layer were determined. Viability of the bacteria and the intestinal epithelial cells after culture with SNP or SNAP were also determined. Both SNP and SNAP at .1 or 1 mmol/L increased the number of viable bacteria internalized into the enterocytes. Both 1 or 10 mmol/L SNP promoted bacterial passage through the intestinal epithelial layer. However, 10 mmol/L SNP decreased the number of viable Caco-2 cells and failed to increase the bacterial internalization into Caco-2 cells. Incubation of E. coli with SNAP at 10 mmol/L slightly decreased the number of viable bacteria and failed to increase the bacterial internalization into Caco-2 cells. We conclude that NO donors promote both the viable bacterial uptake and passage through the intestinal epithelial layer.

Bacterial Translocation↗
PubMed1995

Small intestinal absorption of polyethylene glycol 400 to 1,000 in the portacaval shunted rat.

Functional changes of the intestinal barrier that may occur after the creation of a portacaval shunt (PCS) were investigated. After chronic PCS in the rat, the intestinal absorption of and the jejunal permeability to the inert polymer marker polyethylene glycol (PEG) with molecular weight (Mw) ranging from 400 to 1,000 g/mol were investigated. The PEG mixture was orally fed to PCS and sham-operated rats, and urine was collected for 24 hours to obtain the urinary recovery of the different PEG polymers as a measure of intestinal absorption. To study the intestinal permeability, segments from the proximal small intestine were incubated in diffusion chambers with the PEG mixture on the mucosal side, and samples were withdrawn from the serosal side for analysis. The urinary recovery for the PEGs increased (P < .01) while the tissue permeability decreased (P < .001) in the PCS group rats in comparison with Sham-operated rats. The increased absorption in vivo was caused neither by altered renal clearance, nor by changed portal blood pressure. The decreased jejunal permeability in the PCS rats could be explained by a reduction of the mucosal area by shortening of the microvilli. This discrepancy indicates that changes in permeability and absorption may not be parallel during PCS. It is possible that these changes also may be affected by nutritional factors, drug therapy, as well as toxic substances.

Animals↗