The role of L-arginine and inducible nitric oxide synthase in intestinal permeability and bacterial translocation.

BACKGROUND: Arginine has been shown to have several immunological and trophic properties in stressful diseases. Its metabolites, nitric oxide (NO) and polyamines, are related to arginine's effects. Thus, the aim of this study was to determine the effects of the NO donor L-arginine and the role of inducible NO synthase (iNOS) on intestinal permeability and bacterial translocation in a model of intestinal obstruction (IO) induced by a simple knot in the terminal ileum. MATERIAL AND METHODS: Male C57BL6/J wild-type (WT) and iNOS knockout (iNOS-/-) mice were randomized into 6 groups: Sham and Sham-/- (standard chow), IO and IO-/- (standard chow +IO), and Arg and Arg-/- (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chows, IO was induced and intestinal permeability and bacterial translocation were evaluated. The small intestine and its contents were harvested for histopathological and morphometric analysis and the determination of polyamine concentration. RESULTS: Pretreatment with arginine maintained intestinal permeability (P > .05; Arg and Arg-/- groups vs Sham and Sham-/- groups), increased polyamine concentration in intestinal content (P < .05; Arg vs IO group), and decreased bacterial translocation in WT animals (Arg group vs IO and IO-/- groups). Absence of iNOS also presented a protective effect on permeability but not on bacterial translocation. CONCLUSION: Arginine supplementation and synthesis of NO by iNOS are important factors in decreasing bacterial translocation. However, when intestinal permeability was considered, NO had a detrimental role.

Glutamine supplementation decreases intestinal permeability and preserves gut mucosa integrity in an experimental mouse model.

BACKGROUND: Glutamine (GLN) is the preferred fuel for enterocytes, and GLN supplementation is critical during stressful conditions. The aim of this study was to evaluate the effect of GLN on intestinal barrier permeability and bacterial translocation in a murine experimental model. METHODS: Swiss male mice (25-30 g) were randomized into 3 groups: (1) sham group; (2) intestinal obstruction (IO) group; (3) IO and GLN (500 mg/kg/d) group. Two different experiments were carried out to assess intestinal permeability and bacterial translocation. In the first experiment, the animals were divided into the 3 groups described above and received diethylenetriamine pentaacetate radiolabeled with technetium ((99m)Tc) on the eighth day. At different time points after intestinal obstruction, blood was collected to determine radioactivity. The animals were killed, and the small intestine was removed for histological analyses. In the bacterial translocation study, on the eighth day all groups received Escherichia coli labeled with (99m)Tc. After 90 minutes, the animals underwent intestinal obstruction and were killed 18 hours later. Blood, mesenteric lymph nodes, liver, spleen, and lungs were removed to determine radioactivity. Statistical significance was considered when P < or = .05. RESULTS: The levels of intestinal permeability and bacterial translocation were higher in the IO group than in the sham and GLN groups (P < .05). GLN decreased intestinal permeability and bacterial translocation to physiologic levels in the treated animals and preserved intestinal barrier integrity. CONCLUSIONS: GLN had a positive impact on the intestinal barrier by reducing permeability and bacterial translocation to physiologic levels and preserving mucosal integrity.

Nalidixic acid-resistant Salmonella enterica serotype typhi infection presenting with sub-intestinal obstruction and mesenteric adenitis.

Nalidixic acid-resistant Salmonella typhi NARST infections increase minimal inhibitory concentrations of fluoroquinolones, due to chromosomal mutations in the gene encoding DNA gyrase, and can lead to a delayed treatment response. This in turn alters the course of the disease allowing for a protracted period of illness and the occurrence of complications. In this case report, we present a patient from the Indian sub-continent, who was diagnosed with NARST complicated by sub-intestinal obstruction, her diagnosis, treatment, and subsequent recovery.

The impact of arginine on bacterial translocation in an intestinal obstruction model in rats.

BACKGROUND & AIMS: Arginine has been shown to have multiple beneficial metabolic and immunologic effects in stress situations. Supplementation of arginine has been shown to promote wound healing and intestinal mucosal recovery after trauma, ischemia or intestinal resection. Bacterial translocation has also been evaluated although with conflicting results and using different assessing techniques. Therefore, the aim of this study was to evaluate the effects of arginine on bacterial translocation in an intestinal obstruction model in rats using Escherichia coli labeled with 99mTechnetium. METHODS: Male Wistar rats (250-350 g) were randomized to receive conventional chow, diet supplemented with pure arginine or diet supplemented with an immunonutrition enteral formula, enriched with arginine, omega-3 fatty acid and RNA. After 7 days, the animals were anesthetized. Terminal ileum was isolated and a ligature was placed around it. E. coli labeled with 99mTechnetium (99mTc-E. coli) was inoculated into the intestinal lumen (terminal ileum). After 24 h, the animals were sacrificed. Blood, mesenteric lymph nodes (MLN), liver, spleen and lungs were removed for radioactivity determination. RESULTS: Arginine supplementation (300 mg/day, 600 mg/day or present in the enteral formula) reduced the level of bacterial translocation when compared with the control group (p<0.05). This was shown by significantly decrease uptake of 99mTc-E. coli in blood, MLN, liver, spleen and lungs of the animals in the experimental groups (p < 0.05). CONCLUSIONS: These results have shown that arginine was able to decrease bacteria translocation despite intestinal obstruction. There are several mechanisms which might explain the role of arginine and these will be the subject of future studies.

Supplementation and inhibition of nitric oxide synthesis influences bacterial transit time during bacterial translocation in rats.

In the obstructed gut, nitric oxide (NO) may influence intestinal barrier function and translocation of bacteria. By using a novel experimental approach, we investigated the effect of supplementation and inhibition of NO synthesis on the time interval necessary for translocation of green fluorescent protein-transfected Escherichia coli (GFP-uv E. coli) in a rat model of small bowel obstruction. In anesthetized Wistar rats, 4 x 10(8) GFP-uv E. coli were administered into a reservoir of terminal ileum formed by ligature. Animals were randomized to receive either i.v. arginine (10 mg/kg), aminoguanidine (300 mg/kg), L-NAME (25 mg/kg), or saline (control). Translocation of GFP-uv E. coli was assessed using intravital video microscopy. Minimal transit time of translocation was measured as time from injection of GFP-uv E. coli into the gut lumen until bacteria were observed in the lamina submucosa and as time from injection of bacteria into the gut lumen until bacteria were observed in the lamina muscularis propria. Minimal transit times were expressed as mean +/- SD. Bacterial translocation into the submucosa and muscularis propria took 36 +/- 7 min and 81 +/- 9 min, respectively in control animals receiving saline. Aminoguanidine and L-NAME caused a marked delay of minimal transit time into the submucosa (63 +/- 5 min and 61 +/- 7 min, respectively; P < 0.05). Arginine significantly accelerated bacterial translocation into the muscularis propria (61 +/- 9 min, P < 0.05). GFP-uv E. coli were detected on frozen sections of small bowel, mesentery, liver, and spleen 2 h after GFP-uv E. coli administration in all animals. A marked upregulation of inducible NO synthase (NOS) in the obstructed bowel segment was demonstrated on immunohistochemistry. The assessment of a newly defined parameter, minimal bacterial transit time, may serve as an additional functional aspect of intestinal barrier function for pathophysiological and pharmacological studies. Aminoguanidine, L-NAME, and arginine were effective in influencing minimal transit time of E. coli during small bowel obstruction.

Hyperbaric oxygen ameliorates bacterial translocation in rats with mechanical intestinal obstruction.

PURPOSE: The aim of this study was to demonstrate bacterial translocation after experimentally induced intestinal obstruction as well as investigate the preventive effects of hyperbaric oxygen on obstruction-induced bacterial translocation in rats. METHODS: Forty Wistar-albino male and female rats were used. Although no procedure was done in the control group (n = 8), hyperbaric oxygen treatment under 2.5 atm absolute for 90 minutes daily was applied for two days in the hyperbaric oxygen group (n = 8). In the sham group (n = 8), after laparotomy the small bowel was only handled gently, and tissue sampling was done 48 hours later. In the obstruction group (n = 8) the ileum was ligated by 5-0 polypropylene just 5 cm proximal to the ileocecal valve. In the obstruction and hyperbaric oxygen group (n = 8), after obstruction hyperbaric oxygen treatment was applied. Forty-eight hours after the procedures, tissue samples from small bowel, mesenteric lymph nodes, spleen, and liver were taken and 1 ml of blood from the portal vein was withdrawn. All samples were cultured for microbiologic examination. RESULTS: Hyperbaric oxygen treatment significantly reduced the endogenous bacterial overgrowth in the small intestine of normal rats. Endogenous bacteria in the small intestine were significantly increased in the obstruction group, and the presence of bacterial overgrowth was proven by bacterial presence on mesenteric lymph nodes, spleen, liver, and blood. Hyperbaric oxygen treatment significantly reduced the endogenous bacterial overgrowth in the small intestine and prevented the bacterial translocation almost completely in obstruction-induced rats. CONCLUSIONS: Intestinal obstruction causes bacterial overgrowth and translocation. Hyperbaric oxygen treatment prevents the bacterial translocation effectively.

Effects of somatostatin analogues and vitamin C on bacterial translocation in an experimental intestinal obstruction model of rats.

The passage of viable endogenous bacteria and their products across the intact intestinal mucosal barrier, disseminating to the mesenteric lymph nodes, peritoneal cavity, spleen, liver, and circulation, is defined as bacterial translocation. Intestinal obstruction induces bacterial translocation due to mucosal disruption, motility dysfunction, and increased intestinal volume, leading to bacterial overgrowth. In a rat model of intestinal obstruction, the effects of both high-dose vitamin C (350 microg/kg), an antioxidant agent known to have a cytoprotective effect in ischemia-reperfusion injury, and somatostatin (20 microg/kg), a gastrointestinal antisecretory agent, in preventing bacterial translocation were studied. Both intestinal and liver samples from the rats was observed, and it was found that the rate of bacterial translocation was 100% in the control group, and only 43% for the rats who were given intraperitoneal vitamin C and somatostatin. The difference was statistically significant. In conclusion, we are convinced that vitamin C and somatostatin analogues may have protective effects against bacterial translocation in mechanical bowel obstruction.

Extensive colonic stricture due to pelvic actinomycosis.

A 36-year-old woman presented with a palpable tender mass at the left lower quadrant of the abdomen. She had suffered from constipation for five years and had a previous history of intrauterine device-use for one year. Preoperative barium enema and abdominopelvic CT showed a compatible finding of rectosigmoid colon cancer or left ovary cancer. She underwent segmental resection of the sigmoid colon along with the removal of left distal ureter, left ovary and salpinx. Pathologic examination revealed actinomycotic abscesses containing sulfur granules. Thereafter, she took parenteral ampicillin (50mg/kg/day) for one month and oral amoxicillin (250mg, tid) for 2 months consecutively. The patient has no specific problems for 6 months after surgical resection and long-term antibiotic therapy. This report may be the first of intrauterine device-associated pelvic actinomycosis involving both sigmoid colon and rectum extensively.