Secondary bile acids have been implicated in colonic carcinogenesis. Transformation of primary into secondary bile acids (7 alpha-dehydroxylation) in the large bowel is a pH-dependent process. Inhibition of this reaction could be achieved by lowering colonic pH. We, therefore, studied the effects of lactulose (a non-absorbable disaccharide), which is capable of acidifying colonic contents, on secondary bile acid metabolism. Because this metabolism is age dependent, lactulose was given (0.3 g kg-1 twice daily for 12 weeks) to nine middle-aged (age 31-54 years; mean 45.7) and ten elderly subjects (age 56-81 years; mean 66.4). Twice before, and after 6 and 12 weeks' lactulose administration, biliary and faecal bile acids, whole gut transit time, faecal weight and dry weight, and faecal pH were recorded. The concentration of (iso)lithocholic and deoxycholic acid in faeces was higher in elderly subjects (P less than 0.05) but the excretion was comparable. After lactulose the concentration and excretion of the major secondary bile acids decreased. The primary bile acid fraction rose from 5% before, to more than 20% after, lactulose (P less than 0.05). Faecal weight increased and faecal dry weight decreased, resulting in a higher faecal water output during lactulose. Whole gut transit time did not change. The faecal pH dropped after 6 (P less than 0.05) and further after 12 weeks' lactulose (P less than 0.05). The percentage deoxycholic acid in bile was higher, and cholic acid lower, in elderly subjects (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

In an in vivo model for isolated limb perfusion, developed previously, adriamycin was observed to induce tumors, mainly rhabdomyosarcomas. The tumor incidence was dose dependent. A low incidence was observed after a pseudophysiological perfusion at low flow rate (LF) and 0.25 hematocrit (LF.25). The drug disappearance from the perfusate at the tumorigenic dose for LF.25 was studied in connection with the drug disappearance at two conditions with a high flow rate (HF) that differed from each other in oxygen supply and hematocrit (0.25, 0.11; codes: HF.25 and HF.11). A similar level of drug disappearance resulted in a tumor in six out of 12 limbs after HF.25 and eight out of 19 HF.11 perfused limbs but in only one tumor in 12 rats after LF.25 perfusion. A mechanism by which the HF perfusion conditions favor the induction of a tumor by adriamycin in perfused skeletal muscle remains to be defined.