3,318 research outputs found
An evaluation of methods to assess the effect of antimicrobial residues on the human gut flora
No full text1. 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
Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved
No full textRed meat and processed meat intake is associated with a risk of colorectal cancer, a major cause of death in affluent countries. Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colorectal cancer. This meta-analysis of prospective cohort studies of colon cancer reporting heme intake included 566,607 individuals and 4,734 cases of colon cancer. The summary relative risk of colon cancer was 1.18 [95%C.I.: 1.06-1.32] for subjects in the highest category of heme iron intake compared with those in the lowest category. Epidemiological data thus show a suggestive association between dietary heme and risk of colon cancer. The analysis of experimental studies in rats with chemically-induced colon cancer showed that dietary hemoglobin and red meat consistently promote aberrant crypt foci, a putative pre-cancer lesion. The mechanism is not known, but heme iron has a catalytic effect on (i) the endogenous formation of carcinogenic N-nitroso compounds and (ii) the formation of cytotoxic and genotoxic aldehydes by lipoperoxidation. A review of evidence supporting these hypotheses suggests that both pathways are involved in heme iron toxicit
Minimum Antibiotic Levels for Selecting a Resistance Plasmid in a Gnotobiotic Animal Model
No full textThe minimum antibiotic concentrations for selecting an R plasmid in vivo were determined in germfree rates colonized by two isogenic strains of Escherichia coli, one of which carried an R plasmid. Seventy groups of three gnotobiotic mice were given low doses of ampicillin, colistin, flumequin, gentamicin, tetracycline, or streptomycin via drinking water for 2 weeks. The equilibrium between susceptible and resistant populations of bacteria was monitored daily in feces and compared with that of control mice given pure water. This model yielded reproducible data, and dose and response were strongly correlated. The minimum selecting doses ranged from 0.9 te 12.8 µg/ml of water, depending on the antibiotic and the R plasmid. The use of mathematical models and complementary in vitro experiments accounted for the effect of the low antibiotic levels
Red meat and colon cancer : should we become vegetarians, or can we make meat safer ?
No full textThe 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
Antibiotic residues and R-plasmid selection: are in vitro methods good models?
No full textThree clones of E. coli, one of which was harbouring a tetracycline resistance plasmid were inoculated together into the stomach of axenic mice. Without antibiotic selective pressure, the R-Plasmid bearing strain became dominant in the faeces of mice, while the R-plasmid free strain was eliminated. When the R-plasmid bearing strain was given to mice 4 days after the inoculation with the R-plasmid free strain, it was repressed and remained at the stable level of 10(4.5) organisms per g of faeces. But a rapid spread of the R-plasmid was observed, tetracycline resistant bacteria become dominant within one day, and replace the tetracycline sensitive E. coli. The tetracycline resistance plasmid did not disadvantage the mediating strain in the gut, even in the absence of antibiotic pressure. In contrast Lebek and Egger (1983), studying the same strains in vitro, found that in a chemostat the plasmid bearing strain was overgrown by the plasmid free strain. These results strongly suggest that in vitro interactions between E. coli strains cannot be directly extrapolated to in vivo conditions. For the determination of the no-effect level of antibiotic residue on the selection of R-factor in the gut, studies should be made in vivo
Energy balance and cancers
No full textEnergy 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
Résistances aux antibiotiques des bactéries intestinales de l'homme : origine non iatrogène. Par Denis Corpet, ingénieur agronome, INRA, thèse de doctorat ès sciences Paris-Sud, 1988
No full textFerrando Raymond. Résistances aux antibiotiques des bactéries intestinales de l'homme : origine non iatrogène. Par Denis Corpet, ingénieur agronome, INRA, thèse de doctorat ès sciences Paris-Sud, 1988. In: Bulletin de l'Académie Vétérinaire de France tome 142 n°1, 1989. p. 49
Contrasting activity profile of two distributed cortical networks as a function of attentional demands
No full textThe original publication is available at http://www.jneurosci.orgThis work was supported by R01 grant MH-073610 from the National Institutes of Health to Denis Paré
Model Systems of Human Intestinal Flora, to Set Acceptable Daily Intakes of Antimicrobial Residues
No full textThe veterinary use of antimicrobial drugs in food producing animals may result in residues in food, that might modify the consumer gut flora. This review compares three model systems that maintain a complex flora of human origin: (i) human flora associated (HFA) continuous flow cultures in chemostats, (ii) HFA mice, and (iii) human volunteers. The "No Microbial Effect Level" of an antibiotic on human flora, measured in one of these models, is used to set the accept¬able daily intake (ADI) for human consumers. Human volunteers trials are most relevant to set microbio¬log¬ical ADI, and may be considered as the "gold standard". However, human trials are very expensive and unethical. HFA chemostats are controlled systems, but tetracycline ADI calculated from a chemostat study is far above result of a human study. HFA mice studies are less expensive and better controlled than human trials. The tetracycline ADI derived from HFA mice studies is close to the ADI directly obtained in human volunteers
Most effective colon cancer chemopreventive agents in rats: a systematic review of aberrant crypt foci and tumor data, ranked by potency
No full textPotential chemopreventive agents for colorectal cancer are assessed in rodents. We speculated that the magnitude of the effect is meaningful and ranked all published agents according to their potency. Data were gathered systematically from 137 articles with the aberrant crypt foci (ACF) end point and from 146 articles with the tumor end point. The potency of each agent to reduce the number of ACF is listed in one table and the potency of each agent to reduce the tumor incidence in another table. Both tables are shown in this review and on a website with sorting abilities (http://www.inra.fr/reseau-nacre/sci-memb/corpet/indexan.html). Potency was estimated as the ratio of the value in control rats to the value in treated rats. From each article, only the most potent agent was kept, except in articles reporting the effect of more than seven agents. Among the 186 agents in the ACF table, the median agent reduced the number of ACF by one-half. The most potent agents to reduce azoxymethane-induced ACF were Pluronic, polyethylene glycol, perilla oil with beta-carotene, and sulindac sulfide. Among the 160 agents in the tumor table, the median agent reduced the tumor incidence in rats by one-half. The most potent agents to reduce the incidence of azoxymethane-induced tumors were celecoxib, a protease inhibitor from soy, difluoromethylornithine with piroxicam, polyethylene glycol, and a thiosulfonate. For the 57 agents present in both tables, a significant correlation (r) was found between the potencies against ACF and tumors (r = 0.45, P < 0.001); without celecoxib, a major outlying point in the correlation, r = 0.68 (P < 0.001, n = 56). In conclusion, this review gathers most known chemopreventive agents, ranks the most promising agents against colon carcinogenesis in rats or mice, and further supports the use of ACF as a surrogate end point for tumors in rats
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