Anti-genotoxic and anti-mutagenic activity of Escherichia coli Nissle 1917 as assessed by in vitro tests.

Anti-genotoxic or anti-mutagenic activity has been described for a number of Gram-positive probiotic bacterial species. Here we present evidence that Gram-negative Escherichia coli Nissle 1917 (EcN) also displays anti-genotoxic/anti-mutagenic activity, as assessed in vitro by the Comet Assay and the Ames Test, respectively. This activity was demonstrated by use of the mutagens 4-nitroquinoline-1-oxide (NQO), hydrogen peroxide (H2O2) and benzo(a) pyrene (B[a]P). For both assays and all three test agents the anti-genotoxic/anti-mutagenic activity of EcN was shown to be concentration dependent. By the use of extracts of bacteria that were inactivated by various procedures (heat treatment, ultrasound sonication or ultraviolet light irradiation), mechanistic explanations could be put forward. The proposed mechanisms were enforced by treating the bacterial material with proteinase K prior to testing. The mutagen H2O2 is most likely inactivated by enzymic activity, with catalase a likely candidate, while several explanations can be put forward for inactivation of B[a]P. NQO is most likely inactivated by metabolising enzymes, since the formation of the metabolite 4-aminoquinoline could be demonstrated. In conclusion, the in vitro results presented here make a strong case for antimutagenic properties of EcN.

Fibrinolysis-adjusted perioperative low-dose aprotinin reduces blood loss in bypass operations.

BACKGROUND: Postoperative bleeding still remains a serious problem in bypass surgery. This study evaluated fibrinolysis and perioperative low-dose antifibrinolytic regimens adjusted to the time course of fibrinolysis. METHODS: In a prospective, randomized study of 42 patients undergoing bypass grafting, patients received low-dose aprotinin (group A; n = 14) or low-dose tranexamic acid (group TA; n = 14) intraoperatively and postoperatively, respectively, with no antifibrinolytics for comparison (group C; n = 14). Parameters of procoagulation, fibrinolysis, and activated factor VII were measured preoperatively, intraoperatively, and postoperatively. Blood loss was determined up to 24 hours. RESULTS: The level of thrombin-antithrombin III complex was significantly decreased postoperatively in the treatment groups (group A and TA versus C: 25 +/- 14 and 19 +/- 10 microg/L, respectively, versus 40 +/- 21 microg/L; p < 0.05). Levels of plasmin-antiplasmin complexes were significantly decreased postoperatively in group A (607 +/- 231 microg/L) versus group C (825 +/- 225 microg/L) (p < 0.05) but were increased in group TA (1,145 +/- 394 microg/L) versus group C (p < 0.05). At all times intraoperatively and postoperatively, levels of D-dimers were significantly decreased in group A and group TA versus control (p < 0.001), indicating that fibrinolysis persists after the operation. Intraoperatively, the factor VIIa level decreased significantly in group A (20 +/- 8 mU/mL) versus group C (31 +/- 15 mU/mL) (p < 0.05), but not in group TA (32 +/- 15 mU/mL). Blood loss was significantly lower in group A (135 +/- 37 mL) and group TA (155 +/- 71 mL) versus group C (354 +/- 170 mL) (p < 0.001). CONCLUSIONS: This low-dose aprotinin regimen adjusted to perioperative fibrinolysis reduces blood loss significantly in coronary bypass grafting. For further progress in this subject, clinical investigations of individual fibrinolysis-adjusted antifibrinolytic treatment seems warranted.