The preventive effect of the probiotic Lactobacillus plantarum 299v on bacterial translocation (BT) and the role of adhesion were studied in septic rats. Five groups of rats were pretreated as follows: negative and positive control groups received regular drinking water; the oatmeal group received drinking water mixed with oatmeal; the Lp 299v group received drinking water mixed with oatmeal containing 10(9) colony-forming units (CFU) L. plantarum 299v/ml; the Lp 299v-adh(-) group received drinking water with oatmeal containing 10(9) CFU/ml of modified L. plantarum 299v (L. plantarum 299v-adh(-)) lacking adhesive properties to enterocytes. On day 8, all rats except the negative control group were given lipopolysaccharide (LPS) intraperitoneally. After 24 h, mesenteric lymph node (MLN), liver and ileum were harvested for culture. Incidence of BT after LPS challenge was 25% and 88% in MLN and liver, respectively. BT increased to 75% in MLN and 100% in liver of endotoxemic rats pretreated with oatmeal. Pretreatment with L. plantarum 299v reduced BT to 0% and 12% in MLN and liver, respectively. L. plantarum 299v-adh(-) did not prevent BT to MLN. Flow cytometry revealed reduced adherence of these bacteria to intestinal epithelial cells compared to L. plantarum 299v. Thus, L. plantarum 299v prevents BT in septic rats, an effect probably dependent on bacterial adherence to the intestinal mucosa. Further, our findings indicate that oatmeal (prebiotics) without probiotics does not prevent BT during sepsis.

The major aim of this study was to investigate the CYP3A4 metabolism and polarized transport of ropivacaine and its metabolite 2',6'-pipecoloxylidide (PPX) in tissue specimens from the human small and large intestine. Ropivacaine has been shown to be effective in the treatment of ulcerative colitis in human colon. This study was conducted using a modified Ussing-chamber technique with specimens from jejunum, ileum and colon collected from 11 patients. The local kinetics of ropivacaine and PPX were assessed from their concentration-time profiles in mucosal and serosal compartments. The permeability (P(app)) in the absorptive direction for both ropivacaine and PPX increased regionally in the order jejunum < ileum < colon. Ropivacaine was not found to be subjected to any carrier-mediated intestinal efflux. However, the CYP3A4 metabolite left the human enterocyte in a polarized manner and both the extent of CYP3A4 metabolism of ropivacaine and the extrusion of its metabolite to the mucosal chamber were more efficient in jejunum than in ileum. P-glycoprotein was probably not involved in the metabolite extrusion. No other metabolite than PPX was found. This in-vitro study with human intestinal tissues provides new mechanistic insights into regional transport and metabolism of drugs.

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