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

Antagonistic Effect of Intestinal Bacteria from the Microflora of Holoxenic (Conventional) Piglets, Against Clostridium Perfringens in the Digestive Tract of Gnotoxenic Mice and Gnotoxenic Piglets

Antagonistic effect of piglet microflora against Clostridium perfringens was studied in germfree mice, to isolate bacterial strains responsible for this colonization resistance. The 1:100 dilution of the feces of a 2 day-old conventional piglet, given per os to germfree mice already harboring C. perfringens, led to the elimination of C. perfringens. From this piglet flora, 8 bacterial strains were selected, belonging to the genera Bacteroides, Clostridium, Eubacterium, Bifidobacterium, Lactobacillus and a strain belonging to the class of Mollicutes. When the 8 strains were given to germfree mice 3 days after C. perfringens inoculation, they led to rapid elimination of C. perfringens from feces. Sixteen other mixtures of 2 to 7 strains were similarly tested, but none was able to fully antagonize C. perfringens. When the 8 strains were given per os to germfree piglets after C. perfringens inoculation, they led to the rapid elimination of C. perfringens from pig feces, and to a quick recovery from diarrhea. This study led to the identification of a simplified fraction of gut microflora, able to exert a barrier effect against C. perfringens comparable to the entire flora of the piglet. This study suggests that gnotoxenic mice can be a suitable model for simplifying the flora responsible for a given effect in another host, animal or human

Transverse Spin Diffusion in a Dilute Spin-Polarized Degenerate Fermi Gas

We re-examine the calculation of the transverse spin-diffusion coefficient in a dilute degenerate spin-polarized Fermi gas, for the case of s-wave scattering. The special feature of this limit is that the dependence of the spin diffusion coefficient on temperature and field can be calculated explicitly with no further approximations. This exact solution uncovers a novel intermediate behavior between the high field spin-rotation dominated regime in which $D_{\bot} \propto H^{-2}$, $D_{\parallel} \propto T^{-2}$, and the low-field isotropic, collision dominated regime with $D_{\bot} = D_{\parallel} \propto T^{-2}$. In this intermediate regime, $D_{\bot ,\parallel} \propto T^{-2}$ but $D_{\bot} \neq D_{\parallel}$. We also present an analytical calculation of the self-energy in the s-wave approximation for a dilute spin-polarized Fermi gas, at zero temperature. This emphasizes the failure of the conventional Fermi-liquid phase space arguments for processes involving spin flips. We close by reviewing the evidence for the existence of the intermediate regime in experiments on weakly spin-polarized $^3{\rm He}$ and $^3{\rm He} - ^4{\rm He}$ mixtures.Comment: 38 pages, Latex-Revtex, 9 PostScript figures. Minor revisions, misprints corrected, references adde

The effect of bambermycin, carbadox, chlortetracycline and olaquindox on antibiotic resistance in intestinal coliforms: a new animal model

Groups of germ-free mice kept in isolators and associated with faecal microflora from piglets were continuously given either water or a solution of one of the following: chlortetracycline (20 micrograms/ml), carbadox (50 micrograms/ml), olaquindox (50 micrograms/ml), bambermycin (flavomycin) (5 micrograms/ml) or mixtures of these drugs. The proportions of lactose-fermenting bacteria in their faeces which were resistant to chlortetracycline, carbadox or olaquindox were measured by a comparative plate-counting procedure. Compared to occurrence in control mice, the occurrence of antimicrobial drug-resistant bacteria was higher in mice receiving chlortetracycline (P less than 0.001) and lower in mice receiving bambermycins (P less than 0.005). In contrast, olaquindox and carbadox did not change the proportion of resistant coliforms in mice faeces. A control experiment was conducted with five groups of germ-free mice given the same flora and kept without drugs in separate isolators. No difference in the occurrence of resistant coliforms could be found between these groups. The germ-free mouse associated with faecal microflora from a conventional animal seems to be a suitable model for determining in vivo the effect of low doses of antimicrobial drugs on drug resistance in lactose-fermenting enteric flora

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

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

Antibiotic resistance from food

Antimicrobial resistant Escherichia coli are found in most fecal samples from the normal population. The present study tested the hypothesis that antibiotic-resistant bacteria come from contaminated food. Six healthy volunteers ate a sterile diet for 3 weeks after a control period. The fecal incidence of resistance to ampicillin, tetracycline, and streptomycin in lactose-fermenting enteric bacilli was determined daily. During the control period, the populations of fecal resistant lac+ enteric bacilli varied with time, periodically reaching a high level of 108 per gram. After the start of the sterile diet, the fecal concentration of resistant bacteria dropped. Three days later, no resistant strain could be detected in the feces of three volunteers, whereas in those of the other three, some could be detected sporadically. The sterile diet reduced the number of resistant bacilli in all volunteers (p<0.001). Thus, most fecal resistant lac+ enteric bacilli come from contaminated food: transient strains enter the intestines with food and are excreted in feces

Poverty effects of higher food prices : a global perspective

The spike in food prices between 2005 and the first half of 2008 has highlighted the vulnerabilities of poor consumers to higher prices of agricultural goods and generated calls for massive policy action. This paper provides a formal assessment of the direct and indirect impacts of higher prices on global poverty using a representative sample of 63 to 93 percent of the population of the developing world. To assess the direct effects, the paper uses domestic food consumer price data between January 2005 and December 2007--when the relative price of food rose by an average of 5.6 percent --to find that the implied increase in the extreme poverty headcount at the global level is 1.7 percentage points, with significant regional variation. To take the second-order effects into account, the paper links household survey data with a global general equilibrium model, finding that a 5.5 percent increase in agricultural prices (due to rising demand for first-generation biofuels) could raise global poverty in 2010 by 0.6 percentage points at the extreme poverty line and 0.9 percentage points at the moderate poverty line. Poverty increases at the regional level vary substantially, with nearly all of the increase in extreme poverty occurring in South Asia and Sub-Saharan Africa.Rural Poverty Reduction,Food&Beverage Industry,Poverty Lines,Emerging Markets

Effect of Meat (Beef, Chicken, Bacon) on Rat Colon Carcinogenesis

High intake of red meat or processed meat is associated with increased risk of colon cancer. In contrast, consumption of white meat (chicken) is not associated with risk and might even reduce the occurrence of colorectal cancer. We speculated that a diet containing beef or bacon would increase and a diet containing chicken would decrease colon carcinogenesis in rats. One hundred female Fischer 344 rats were given a single injection of azoxymethane (20 mg/kg i.p.), then randomized to 10 different AIN-76-based diets. Five diets were adjusted to 14% fat and 23% protein and five other diets to 28% fat and 40% protein. Fat and protein were supplied by 1) lard and casein, 2) olive oil and casein, 3) beef, 4) chicken with skin, and 5) bacon. Meat diets contained 30% or 60% freeze-dried fried meat. The diets were given ad libitum for 100 days, then colon tumor promotion was assessed by the multiplicity of aberrant crypt foci [number of crypts per aberrant crypt focus (ACF)]. The ACF multiplicity was nearly the same in all groups, except bacon-fed rats, with no effect of fat and protein level or source (p = 0.7 between 8 groups by analysis of variance). In contrast, compared with lard- and casein-fed controls, the ACF multiplicity was reduced by 12% in rats fed a diet with 30% bacon and by 20% in rats fed a diet with 60% bacon (p < 0.001). The water intake was higher in bacon-fed rats than in controls (p < 0.0001). The concentrations of iron and bile acids in fecal water and total fatty acids in feces changed with diet, but there was no correlation between these concentrations and the ACF multiplicity. Thus the hypothesis that colonic iron, bile acids, or total fatty acids can promote colon tumors is not supported by this study. The results suggest that, in rats, beef does not promote the growth of ACF and chicken does not protect against colon carcinogenesis. A bacon-based diet appears to protect against carcinogenesis, perhaps because bacon contains 5% NaCl and increased the rats' water intak