Intestinal mucosal oxidative damage and bacterial translocation in cirrhotic rats.

BACKGROUND: Bacterial translocation plays an important role in the pathogenesis of spontaneous bacterial peritonitis mainly due to intestinal bacterial overgrowth. Alterations in the functional integrity of the intestinal barrier caused by an increased production of free radical metabolites as a consequence of portal hypertension could also facilitate bacterial translocation in cirrhotic rats. OBJECTIVE: The aim of the study was to determine intestinal mucosal lipid peroxidation and neutrophil infiltration and their relationship with portal hypertension and bacterial translocation in cirrhotic rats. DESIGN: Eighteen male Sprague-Dawley rats with cirrhosis induced by carbon tetrachloride, administered by gavage, and eight control rats were included in the study. METHODS: Samples of jejunum, ileum and caecum were obtained by laparotomy for the determination of malondialdehyde and myeloperoxidase as indexes of lipid peroxidation and neutrophil infiltration, respectively. Samples of ascitic and pleural fluids, mesenteric lymph nodes and ileal stools were obtained for the culture of microoganisms. RESULTS: The concentration of malondialdehyde was significantly higher in ileal and caecal, but not in jejunal mucosa, in cirrhotic rats, mainly in those with ascites (P< 0.01), as compared to control rats (P< 0.01), and in cirrhotic rats with bacterial translocation compared to those without bacterial translocation (P< 0.01). No differences between groups were observed in the concentrations of myeloperoxidase in jejunum, ileum or caecum. A direct correlation between ileal malondialdehyde and portal pressure was observed (P< 0.01). CONCLUSIONS: Cirrhotic rats, particularly those with ascites and bacterial translocation, show increased malondialdehyde levels in ileal and caecal mucosa. These results suggest that mucosal oxidative damage in ileum and caecum could favour bacterial translocation in cirrhotic rats.

[Wireless capsule endoscopy: basic principles and clinical utility]. / Cápsula endoscópica: fundamentos y utilidad clínica.

Wireless capsule endoscopy (PillCam) represents a major advance in the study of small bowel disease since this procedure allows images of hitherto unreachable areas to be obtained. Approved for use by the Food and Drug Administration in August 2000, capsule endoscopy is currently a first line procedure in the study of small bowel disease. This technique consists of a non-reusable swallowable capsule (length 26 x 11 mm) that acquires video images while moving through the gastrointestinal tract propelled by natural peristalsis. The main indications of capsule endoscopy are evaluation of obscure gastrointestinal bleeding, chronic anemia, and inflammatory bowel disease. Contraindications are swallowing disorders and known or suspected small bowel strictures of any etiology. Consequently, small bowel follow through is useful prior to capsule endoscopy when these lesions are suspected.

Bacterial translocation is downregulated by anti-TNF-alpha monoclonal antibody administration in rats with cirrhosis and ascites.

BACKGROUND/AIMS: TNF-alpha is involved in the development of bacterial translocation in rats with cirrhosis. The aim of the current study was to evaluate the effect of anti-TNF-alpha mAb treatment on the incidence of bacterial translocation and systemic infections in rats with cirrhosis and ascites. METHODS: Thirty rats with cirrhosis and ascites were randomly assigned to receive two intraperitoneal doses of anti-TNF-alpha mAb, distilled water or immunoglobulin on days 0 and 4. On day 10, a laparotomy was performed. RESULTS: One out of 11 animals receiving anti-TNF-alpha mAb treatment, 7 out of 10 of the placebo group (p<0.01), and 5 out of 9 of the IgG group developed bacterial translocation (p<0.05). A significantly reduced number of systemic infections were observed in animals receiving anti TNF-alpha mAb treatment vs animals receiving placebo (p<0.01). TNF-alpha in serum at laparotomy in animals receiving anti-TNF-alpha mAb was higher than that in the rest of groups and was also higher in the overall series of animals showing bacterial translocation. CONCLUSIONS: In the experimental model of CCl(4)-induced rat with cirrhosis and ascitic fluid, anti-TNF-alpha mAb administration decreases the incidence of bacterial translocation, in a TNF-alpha/sTNF-alpha receptor-independent manner, without increasing the risk of systemic infections.

Development of an experimental model of induced bacterial peritonitis in cirrhotic rats with or without ascites.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhotic patients associated with a high mortality. AIM: To develop an available experimental model of induced bacterial peritonitis in cirrhosis. MATERIAL AND METHODS: Sprague-Dawley rats with carbon-tetrachloride-induced cirrhosis with (N=22) or without (N=101) ascites were randomized to receive an intraperitoneal administration of different concentrations of Escherichia coli (E. coli) diluted in 1 mL of sterile water in ascitic rats and in different volumes in nonascitic rats. A subgroup of nonascitic animals received ceftriaxone 4 h after E. coli inoculation. Mortality of rats was evaluated 24 h after bacterial inoculation. RESULTS: None of the rats receiving sterile water alone and only one infected with 10(7) cfu of E. coli died. Ascitic rats showed a lower mortality rate than nonascitic rats infected with 10(8) or 10(9) cfu of E. coli (P<0.05). Mortality was higher with 10(9) cfu than with 10(8) cfu of E. coli in ascitic (P NS) and nonascitic (P<0.01) rats. A trend was noted to ward higher mortality in nonascitic rats inoculated with 10(8) cfu with increasing water volumes. A marked peritoneal polymorphonuclear cell response was observed 4 h after E. coli injection in both ascitic and nonascitic rats. Antibiotic therapy significantly reduced the mortality rate of rats infected with 10(8) cfu (P<0.01). CONCLUSIONS: This experimental model of induced bacterial peritonitis in cirrhosis with or without ascites may represent a useful tool for the study of pathogenic events postinfection and for the design of new therapeutic strategies to treat patients with SBP.

The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation.

Bacterial DNA (bactDNA) is present in blood and ascitic fluid (AF) in a third of patients with cirrhosis and ascites, but whether this phenomenon represents episodes of bacterial translocation (BT), strictly considered when culture of mesenteric lymph nodes (MLNs) are positive, remains unknown. This study assessed the relationship between bactDNA detection in biological fluids and MLNs and went on to investigate the local and systemic inflammatory status according to its presence. Cirrhosis was induced in rats by ingestion of CCL4. A subgroup of five animals with cirrhosis received norfloxacin (5 mg/kg/day) for 7 days. MLNs and ascitic and pleural fluids were collected at laparotomy and cultured; samples were collected for identification of bactDNA and measurement of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO). BactDNA was detected in MLNs in 12 of 19 animals (63.1%), corresponding in seven cases to culture-positive MLNs, and in five to culture-negative MLNs. BactDNA was detected in biological fluids in 11 of 19 animals (57.9%), and in all cases the same bacteria spp. detected in samples was present in MLNs. BactDNA was not detected in any biological sample from animals receiving norfloxacin. Tumor necrosis factor alpha (TNF-alpha), IL-6, and NO were similar in culture-positive and culture-negative/bactDNA-positive samples, and significantly higher than those observed in animals with culture-negative/bactDNA-negative MLNs, animals with cirrhosis that were receiving norfloxacin, and controls. In conclusion, the presence of bactDNA in biological fluids in rats with cirrhosis constitutes a marker of BT, and it is associated with a marked inflammatory response, independent of the result of the culture.

Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: a double-blind RCT.

Nonselective beta-blockers are very effective in preventing first variceal bleeding in patients with cirrhosis. Treatment with isosorbide-5-mononitrate (IS-MN) plus propranolol achieves a greater reduction in portal pressure than propranolol alone. The present multicenter, prospective, double-blind, randomized, controlled trial evaluated whether combined drug therapy could be more effective than propranolol alone in preventing variceal bleeding. A total of 349 consecutive cirrhotic patients with gastroesophageal varices were randomized to receive propranolol + placebo (n = 174) or propranolol + IS-MN (n = 175). There were no significant differences in the 1- and 2-year actuarial probability of variceal bleeding between the 2 groups (propranolol + placebo, 8.3% and 10.6%; propranolol + IS-MN, 5% and 12.5%). The only independent predictor of variceal bleeding was a variceal size greater than 5 mm. However, among patients with varices greater than 5 mm (n = 196), there were no significant differences in the incidence of variceal bleeding between the 2 groups. Survival was also similar. Adverse effects were significantly more frequent in the propranolol + IS-MN group due to a greater incidence of headache. There were no significant differences in the incidence of new-onset or worsening ascites or in impairment of renal function. In conclusion, propranolol effectively prevents variceal bleeding. Adding IS-MN does not further decrease the low residual risk of bleeding in patients receiving propranolol. However, the long-term use of this combination drug therapy is safe and may be an alternative in clinical conditions associated with a greater risk of bleeding.