An evaluation of methods to assess the effect of antimicrobial residues on the human gut flora

1. Barrier effect. Relevant models should include an anaerobic dominant flora that antagonizes minor bacterial populations such as drug resistant E. coli. 2. Anaerobes vs. aerobes. Aerobe counts are more precise and much less time consuming than anaerobe counts. Minor populations of drug resistant aerobes are sensitive markers of the ecosystem balance, and are directly relevant to the potential risk of antimicrobial residues. 3. MIC vs. plate counts. The determination of minimum inhibitory concentrations ( MIC ) of selected clones is time consuming, does not detect subdominant resistance (less than 1 %), and the MIC shift is difficult to test statistically. In contrast, direct counts of bacteria on drug supplemented media allows a rapid measure of minor resistant populations. 4. Statistics: Most published designs do not include adequate statistical evaluation. This is critical for trials made in conventional humans and animals, where data are highly variable. 5. Human trials: The lowest concentration of antibiotic tested in human volunteers (2mg oxytetracycline /d for 7d in 6 subjects) significantly increased the proportion of resistant fecal enterobacteria (P=0.05). However, the huge day-to-day and inter-individual variations of human floras make this evidence rather weak. 6. Gnotobiotic mice inoculated with human flora are living isolated models in which the effect of any antimicrobial on the human gut flora can be tested. This in vivo model does include the barrier effect of dominant anaerobes. Inter-individual and day-to-day variations of bacterial populations are lower in those mice than in humans. 7. Most resistant enterobacteria in the human gut of untreated people come from bacterial contamination of raw foods. The relative contribution of residues in selecting antibiotic resistance seems to be low when compared to bacterial contamination

Red meat and colon cancer : should we become vegetarians, or can we make meat safer ?

The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer

Energy balance and cancers

Energy balance results from the exact equilibrium between caloric intake and caloric expenditure. A caloric intake larger than caloric expenditure results in overweight, even obesity, but other determinants, like hormonal dysfunction and/or genetic traits may play a part in obesity syndrome. Obesity, and even overweight, have been recognized as risk factors for the development of cancers. Human epidemiological studies, which have tended to establish the nature of the relationship between energy balance and cancer, are summarized first, with the influence of the various factors which act both on obesity and on cancer risk. Among these factors are the macronutrients responsible for the caloric intake, and some lifestyle factors (physical activity, drinking habits and tobacco use). Second, the animal studies help to distinguish between different relevant factors, and to understand some of the underlying mechanisms. However, the insulin-resistance syndrome, which appears to underlie the relationship between obesity and hormone-dependent cancers, and possibly colon cancer, is only relevant to human physiology because hormonal alterations are part of it. Prevention of hyperinsulinemia, insulin resistance and the accompanying visceral obesity appears to be a major public health task for the prevention of cancers

Point: From animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system.

The Apc(Min/+) mouse model and the azoxymethane (AOM) rat model are the main animal models used to study the effect of dietary agents on colorectal cancer. We reviewed recently the potency of chemopreventive agents in the AOM rat model (D. E. Corpet and S. Tache, Nutr. Cancer, 43: 1-21, 2002). Here we add the results of a systematic review of the effect of dietary and chemopreventive agents on the tumor yield in Min mice. The review is based on the results of 179 studies from 71 articles and is displayed also on the internet http://corpet.net/min.(2) We compared the efficacy of agents in the Min mouse model and the AOM rat model, and found that they were correlated (r = 0.66; P < 0.001), although some agents that afford strong protection in the AOM rat and the Min mouse small bowel increase the tumor yield in the large bowel of mutant mice. The agents included piroxicam, sulindac, celecoxib, difluoromethylornithine, and polyethylene glycol. The reason for this discrepancy is not known. We also compare the results of rodent studies with those of clinical intervention studies of polyp recurrence. We found that the effect of most of the agents tested was consistent across the animal and clinical models. Our point is thus: rodent models can provide guidance in the selection of prevention approaches to human colon cancer, in particular they suggest that polyethylene glycol, hesperidin, protease inhibitor, sphingomyelin, physical exercise, epidermal growth factor receptor kinase inhibitor, (+)-catechin, resveratrol, fish oil, curcumin, caffeate, and thiosulfonate are likely important preventive agents

Version Control in Online Software Repositories

Software version control repositories provide a uniform and stable interface to manage documents and their version histories. Unfortunately, Open Source systems, for example, CVS, Subversion, and GNU Arch are not well suited to highly collaborative environments and fail to track semantic changes in repositories. We introduce document provenance as our Description Logic framework to track the semantic changes in software repositories and draw interesting results about their historic behaviour using a rule-based inference engine. To support the use of this framework, we have developed our own online collaborative tool, leveraging the fluency of the modern WikiWikiWeb

Chemoprevention of aberrant crypt foci in the colon of rats by dietary onion

Onion intake might reduce the risk of colorectal cancer, according to epidemiology. However, Femia showed in 2003 that diets with a 20% onion intake increase carcinogenesis in rats. We speculated this dose was too high. Prevention of initiation was thus tested in 60 rats given a 5% dried onion diet or AIN76 diet, and initiated 12 days later with azoxymethane (AOM, 1 × 20 mg/kg i.p.), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 2 × 200 mg/kg p.o.), or N-nitroso–N–methylurea (2 × 50 mg/kg p.o.). Prevention of promotion was tested in 38 rats given AOM, then randomised to: AIN76 diet; 5% onion diet; phytochemicals diet (supplemented with propyl-disulfide, quercetine-glycosides and oligofructose); 1% pluronic F68 diet (a potent chemopreventive PEG-like block-polymer, used as a positive control). Aberrant crypt foci (ACF) were scored 30 days (initiation) or 100 days (promotion) after carcinogen injection. The onion diet given during initiation reduced the number of AOM-induced ACF (60 versus 86, p = 0.03), and the size of IQ-induced ACF (1.33 versus 1.97, p = 0.02). Given post-initiation, the onion diet reduced the number of ACF (34 versus 59, p = 0.008) and of large ACF (6 versus 15, p = 0.02). Phytochemicals diet and pluronic diet reduced ACF growth similarly. Data show that a 5% onion diet reduced carcinogenesis during initiation and promotion stages, and suggest this chemoprevention is due to known phytochemicals