Six healthy, scientifically informed human volunteers were given14C-labeled polyethyleneimine (PEI) microcapsules by mouth. Fecal14C recovery was inversely related to mean gut transit time (r = ...-0.66), and the extent of cross-linking between the membrane and core PEI was inversely related to total fecal output (r = -0.81). Cross-linking of PEI microcapsules may be a biomonitor of endogenous cross-linking agents within the human gastrointestinal tract. Extensive loss of 14C CH3label occurred from the microcapsules during human transit and in in vitro fermentations with human fecal flora. A mechanism whereby reactive oxygen species could arise in the iron-rich core of these microcapsules, leading to loss of 14C CH3label, is proposed.
In 5–15% of the patients with inflammatory bowel disease (IBD) limited to the colon, it is difficult to distinguish histologically between ulcerative and Crohn’s colitis. This is described as ...unclassified colitis. Distinguishing between the two is important in terms of prognosis, since patients with Crohn’s disease (CD) have a higher risk of strictures and fistulae, which may predict a more severe disease course, as well as an increased risk for surgery. In addition, colectomy may be curative in ulcerative colitis patients not responding to medical therapy, while Crohn’s patients undergoing colectomy can have relapses in other areas of the bowel and, therefore, need to be followed-up. In inflammatory bowel disease, intestinal inflammation is believed to occur secondary to an altered immune response in a genetically susceptible host. Genetic and serological markers (antibodies) may have a role in identifying unclassified colitis. Anti-Saccharomyces cerevisiae antibody (ASCA) and anti-neutrophil cytoplasmic antibodies (pANCA) have the highest sensitivity in distinguishing ulcerative from Crohn’s colitis. Nucleotide oligomerization domain 2 (NOD2) and autophagy-related 16-like 1 (ATG16L1) polymorphisms are strongly associated with Crohn’s disease, while epithelial barrier genes are significantly associated with ulcerative colitis. This chapter describes which gene polymorphisms and serological markers may be used to distinguish between ulcerative colitis and Crohn’s disease in patients with histologically unclassified colitis.
Semi-permeable magnetic microcapsules previously shown able to trap gastrointestinal carcinogens and containing polyethyleneimine (PEI) were covalently labelled with 14CH3, and administered for the ...first time to humans (six healthy volunteers, 1.3 microCi/dose) in gelatin capsules together with radio-opaque gut transit markers (ROM), in order both to seek human endogenous cross-linking or bifunctional alkylating agents and assess gut transit features. No ill-effects were reported. Faecal ROM and 14C excretions were well correlated (r = 0.96), and net 14C recovery in faeces was 83-96%. Microcapsules were separated magnetically from faeces and 29-81% of specific labelling of microcapsules (nCi/10(6)) was found to have been removed during GI transit. Label cleavage out of these microcapsules was also found following in vitro anaerobic incubation with faecal slurries from two volunteers. On treatment with H2O2, label was removed selectively from the Fe-containing core in a dose-dependent manner. Therefore, label cleavage in vivo (not observed in rats consuming chow but found notably on consumption of low-fibre and/or high-beef human diets) is likely to arise from low mol. wt substances that give Fenton reaction producing hydroxyl radicals and oxidative demethylation. After GI transit, extensive core to membrane cross-linking in the microcapsules was found and was inversely related to faecal output. Cross-linking also was obtained to a greater extent during in vitro anaerobic incubation with faecal slurries. The GI mucosa would also be exposed to both types of agents, and several features of this microcapsule monitoring are in accord with putative risk-modulating effects. This first use of microcapsules for biomonitoring of the human GI tract thus seemed to be without hazard, and revealed extensive levels of agents likely to cause DNA damage.
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