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Wheat bran decreases aberrant crypt foci, preserves normal proliferation, and increases intraluminal butyrate levels in experimental colon cancer.

BACKGROUND: Dietary wheat bran protects against colon cancer, but the mechanism(s) of this effect is not known. Butyrate, produced by colonic bacterial fermentation of dietary polysaccharides, such as wheat bran, induces apoptosis and decreases proliferation in colon cancer cell lines. Whether similar effects occur in vivo is not well defined. We hypothesized that wheat bran's antineoplastic effects in vivo may be mediated in part by butyrate's modulation of apoptosis and proliferation. METHODS: Male F344 rats were fed wheat bran-supplemented or an isocaloric, isonitrogenous fiber-free diet. Rats were treated with one dose of the carcinogen azoxymethane or vehicle with sacrifice after 5 days (tumor initiation); or two doses (days O and 7) with sacrifice after 56 days (tumor promotion). Study variables included fecal butyrate levels and the intermediate biomarkers of colon carcinogenesis, aberrant crypt foci (ACF), and changes in crypt cell proliferation and apoptosis. RESULTS: During tumor initiation, wheat bran produced greater apoptosis (p = .01), a trend toward less proliferation, and preserved the normal zone of proliferation (p = .01). At tumor promotion, wheat bran decreased the number of ACF (proximal colon, p = .005; distal colon, p = .047) and maintained the normal proliferative zone. The fiber-free diet shifted the zone of proliferation into the premalignant pattern in both studies. Wheat bran produced significantly higher fecal butyrate (p = .01; .004, .00001) levels than the fiber-free diet throughout the tumor promotion study. CONCLUSIONS: Wheat bran increased apoptosis and controlled proliferation during tumor initiation and resulted in decreased ACF. Wheat bran's antineoplastic effects occurred early after carcinogen exposure, and were associated with increased fecal butyrate levels.

Animals↗

Dietary patterns associated with colon and rectal cancer: results from the Dietary Patterns and Cancer (DIETSCAN) Project.

BACKGROUND: An analysis of dietary patterns or combinations of foods may provide insight regarding the influence of diet on the risk of colon and rectal cancer. OBJECTIVE: A primary aim of the Dietary Patterns and Cancer (DIETSCAN) Project was to develop and apply a common methodologic approach to study dietary patterns and cancer in 4 European cohorts: the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (Finland-ATBC), the Netherlands Cohort Study (NLCS) on Diet and Cancer, the Swedish Mammography Cohort (SMC), and the Ormoni e Dieta nella Eziologia dei Tumori (Italy-ORDET). Three cohorts (ATBC, NLCS, and SMC) provided data on colon and rectal cancer for the present study. DESIGN: The cohorts were established between 1985 and 1992; follow-up data were obtained from national cancer registries. The participants completed validated semiquantitative food-frequency questionnaires at baseline. RESULTS: Exploratory factor analysis, conducted within each cohort, identified 3-5 stable dietary patterns. Two dietary patterns-Vegetables and Pork, Processed Meats, Potatoes (PPP)-were common across all cohorts. After adjustment for potential confounders, PPP was associated with an increased risk of colon cancer in the SMC women (quintile 4(multivariate) relative risk: 1.62; 95% CI: 1.12, 2.34; P for trend = 0.01). PPP was also associated with an increased risk of rectal cancer in the ATBC men (quintile 4(multivariate) relative risk: 2.21; 95% CI: 1.07, 4.57; P for trend = 0.05). Neither pattern was associated with the risk of colon or rectal cancer in the NLCS women and men. CONCLUSION: Although certain dietary patterns may be consistent across European countries, associations between these dietary patterns and the risk of colon and rectal cancer are not conclusive.

Adult↗

Diabetes: a candidate disease for efficient DNA methylation profiling.

Methylation has been implied in a number of biological processes and has been shown to vary under environmental influences as well as in age. Most results on the correlation of methylation patterns with phenotypic characteristics of cells have been obtained by analysis of very few or even single genomic fragments for methylation. However, variation of methylation may more often than not be a phenomenon that affects multiple genomic loci. The role of methylation has been most conclusively demonstrated in complex disease, with cancer being the most prominent example. The influence of aging and environmental influences such as diet seems to be on global methylation patterns, in turn exerting local effects on groups of genes. Hence, methylation seems literally to be orchestrating complex genetic systems. It could, therefore, be considered an archetypal "genomics" parameter. In consequence, technologies used to analyze methylation patterns should be as industrialized as possible to capture the local events across the entire genome. Epigenomics' research team is the first to have achieved the industrialized production of genome sequence-specific wide methylation data. Our microarray and mass-spectrometry-based detection platform currently allow the analysis of up to 50,000 methylation positions per day, for the first time making methylation data amenable to sophisticated information mining. The information content of methylation position has never been analyzed using the high-dimensional statistical methods that are recognized to be required for the analysis of, for example, mRNA expression profiles or proteomic data. As methylation patterns are nothing but a quasi-digital form of expression data, their information content must be evaluated using similar but adapted algorithms. This article presents a broad set of studies that demonstrate that methylation yields information that is comparable or even superior to the current state of the art, namely, mRNA profiling. We argue that the resulting robust, digital and-because of the highly stable nature of DNA as the analyte-more reproducible information could become the "gold standard" for clinical diagnostics and disease gene identification in age-related, environmentally influenced and epigenetic disease in general, substituting for mRNA expression.

DNA Methylation↗

Baboon alcohol dehydrogenase isozymes: purification and properties of liver class I ADH. Moderate alcohol consumption reduces liver class I and class II ADH activities.

The major baboon liver isozyme of alcohol dehydrogenase (ADH-2) has been purified to homogeneity by affinity chromatography, and characterized as a "typical" Class I mammalian ADH isozyme. In contrast to human liver, which possesses three genetic isozymes (alpha 2, beta 2, and gamma 2) and three hybrid isozymes (alpha beta, alpha gamma, and beta gamma) of Class I ADH, baboon liver exhibits activity of a single major Class I isozyme (beta 2). Kinetic analyses, using alcohol substrates of differing chain lengths, and inhibition with pyrazole, support this classification. Agarose-IEF analyses, substrate specificity studies and immunochemical titrations of the major kidney ADH (ADH-1) also support the occurrence of a second Class I isozyme. The baboon was used as a model to study alcohol-induced changes in liver ADH phenotype following moderate and moderately high alcohol consumption. Four male and four female prepubertal baboons were fed nutritionally adequate liquid diets over a 40-week period, including control diets (weeks 1-8, 17-24, 32-40), moderate (12.5 percent of calories) alcohol diet (weeks 9-16), and a moderately high (25 percent of calories) alcohol diet (weeks 25-32). Liver ADH isozyme patterns and Class I ADH activities from biopsy samples, taken every 4 weeks, were monitored during the feeding study. Decreases in both Class I and Class II ADH activities were indicated in most animals, which may reflect adaptive mechanisms in the liver to continuing alcohol metabolism. Moreover, reversible changes were observed, with trends toward a recovery of ADH isozyme activities following return to the control liquid diets. These studies also have particular significance for human biomedical research work on alcohol, since most of the "drinking" population in typical drinking communities are moderate consumers of alcohol. This work, using the baboon as an animal model, has clearly indicated that alcohol consumption at such moderate levels, brings with it adaptations in the level of ADH isozymes in liver, which may play a protective role.

Alcohol Dehydrogenase↗

Microsomal triglyceride transfer protein expression in mouse intestine.

Immunohistochemical and biochemical approaches were utilized to compare the expression of microsomal triglyceride transfer protein (MTP) and cellular retinol binding protein II (CRBPII) with the expression of apolipoprotein (apo)B and apoA-I along the entire length of the small intestine in mice. MTP is expressed in villus-associated enterocytes along the length of the small intestine. Maximal expression occurs within the first 20% of the intestine and decreases to less than 3% of maximum in the distal third of the intestine. The expression of CRBPII is nearly identical with that of MTP. Peak expression of apoB and apoA-I occurs in the first 25% of the intestine; however, expression in the most distal segments of the intestine is 10%-15% of maximum expression. In mice fed a Western diet for 3 weeks the expression of MTP and CRBPII was elevated in the distal regions of the intestine, whereas the expression patterns for apoB and apoA-I were similar to those found in mice on control diets. We conclude that the patterns of expression, as well as the regulation of MTP and CRBPII, are similar. However, the expression and regulation of these two proteins differ from those of apoB and apoA-I. In particular, the expression of MTP is not coordinated with the expression of apoB, even though the two proteins are essential for the assembly and secretion of chylomicrons.

Animals↗

A review of energy metabolism in producing ruminants. Part 1: Metabolism of energy substrates.

The efficiency of metabolisable energy utilisation, for growth and fattening, is dependent upon the relative VFA proportions produced in the rumen. Sufficient propionate is required to meet glucose demand for producing NADPH, glycerol and nucleic acid synthesis. Since diet has the greatest effect on the pattern of VFA fermentation, it will play a major role in controlling the supply of VFA to the animal. Magnitude of the acetate supply determines the proportion of acetate supplied to oxidation or to fatty acid synthesis, which is also dependent upon the extracellular supply of glucose, NADPH and ATP. Since the optimal levels of acetate and glucose for lipogenesis appear to vary with glucose concentration, a diet that decreases the supply of glucogenic precursors, but increases the acetate supply, may suppress fatty acid synthesis. An increased supply of propionate may suppress glucose synthesis from other sources. The isoenergetic replacement of roughage by concentrate, appears to increase the glucose entry rate, due to both an increase in propionate, and glucose absorbed from the small intestine. Dietary nitrogen source also affects the rate of gluconeogenesis. An optimum dietary energy-protein ratio exists for maximum efficiency of utilisation of both dietary energy and protein. In dairy cows, for example, the energy is most effectively metabolised when protein content of the diet is 15-25% of net energy.

Animals↗

Background diet influences the anti-inflammatory effect of alpha-linolenic acid in dyslipidaemic subjects.

Long-chain n-3 PUFA from fish oils are known to have anti-inflammatory effects. We evaluated the effect of alpha-linolenic acid (ALA), precursor of n-3 fatty acids, on serum inflammatory markers and soluble cellular adhesion molecules (sCAM) of dyslipidaemic males, relative to their background diet. Participants were assigned to two groups, based upon food intake patterns: (a) twenty-one dyslipidaemic subjects who habitually ate a Mediterranean-Cretan-type diet; (b) nineteen dyslipidaemic subjects who normally ate a Westernised Greek diet. All were supplemented with 8.1 g ALA/d for 12 weeks. We determined serum amyloid A (SAA), C-reactive protein (CRP), macrophage colony-stimulating factor (MCSF), IL-6, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 and soluble E-selectin concentrations at the beginning and the end of the ALA supplementation period. Serum baseline concentrations of inflammatory markers and sCAM were similar across the diet groups. Type of diet had a significant impact on the response of inflammatory markers to ALA supplementation. The Westernised Greek diet group showed a reduction in SAA (P<0.001), CRP (P=0.002), MCSF (P=0.005) and IL-6 (P=0.04) concentrations. The Mediterranean-Cretan-type background diet group showed a significant reduction only in MCSF concentrations (P=0.003). The sVCAM-1 concentrations were significantly reduced in both the Westernised Greek diet group (P=0.001) and the Mediterranean-Cretan-type diet group (P<0.001). The present study demonstrated that ALA supplementation lowered the serum concentrations of inflammatory markers more profoundly when the background diet was rich in saturated fatty acids and poor in MUFA.

Adult↗

Ontogenic and nutritional modifications in the intestinal fucosylation process at the weaning period. Influence of dietary fibers.

In the rat small intestine, the glycosylation changes which normally take place at the weaning period are characterized by a shift from sialylation to fucosylation. The introduction of dietary fibers at weaning is one of the more striking nutritional modification so that some authors have suggested that the presence of fibers and the development of colonic fermentation might be important for the development of the small intestine, as for the colon. In order to define the respective contribution of ontogenic and nutritional factors to the intestinal glycosylation changes at this period, some aspects of the intestinal glycosylation were studied in five groups of rats (16-day-old suckling rats, prolonged nursing 23-day-old rats, 23-day-old rats weaned at day 19 with either a fiber-free, a cellulose or a pectin diet). Intestinal glycoproteins of suckling rats are characterized by a low fucose content and a high proportion of mannose. The amounts of the neutral sugars (fucose, mannose and galactose), expressed either per gram of intestine or for one intestine, are always higher in the fiber-fed groups than in the prolonged-nursing group or the group fed the fiber-free diet. Activities which promote fucosylation process (GDP-fucose production and fucosyltransferase activities) and those which are opposed to fucosylation (endogenous inhibitor of fucosyltransferase and GDP-fucose pyrophosphatase) are strongly modified in opposite ways at day 23 as compared to day 16. These modifications depend on the age of the animal (ontogenic factors) with additional modifications induced by the dietary factors. In particular, similar sugar contents and patterns are obtained with cellulose and pectin diets though the enzymatic activities of the fucosylation pathway are very different. No correlation was found between the caecal content of short chain fatty acids and any of the parameters under study. Thus, dietary fibers induce metabolic changes in the small intestine glycosylation in short-term experiments independently of colonic fermentation. Besides, these results point out that the consideration of fucosyl-transferase activities alone are not sufficient to predict glycoprotein fucose content and that other regulatory sites are involved. Dietary manipulations at the weaning period could represent a good model for the study of glycosylation regulation.

Animals↗

Divergence in proportional fat intake in AKR/J and SWR/J mice endures across diet paradigms.

These experiments were designed to test the hypothesis that the contrasting patterns of macronutrient selection described previously in AKR/J (fat preference) and SWR/J (carbohydrate preference) mice are not dependent on a single diet paradigm. The effect of mouse strain on proportional fat intake was tested in naive mice by presenting two-choice diets possessing a variety of physical, sensory, and nutritive properties. In three separate experiments, AKR/J mice preferentially selected and consumed a higher proportion of energy from the high-fat diet than SWR/J mice. Specifically, this phenotypic difference was observed with 1) fat-protein vs. carbohydrate-protein diets, independent of fat type (vegetable shortening or lard), 2) isocaloric, high- vs. low-fat liquid diet preparations, and 3) high- vs. low-fat powdered-granular diets. These results confirm our previous observation of a higher proportional fat intake by AKR/J compared with SWR/J mice using the three-choice macronutrient selection diet and show that this strain difference generalizes across several diet paradigms. This strain difference is due largely to the robust and reliable fat preference of the AKR/J mice. In contrast, macronutrient preference in SWR/J mice varied across paradigms, suggesting a differential response by this strain to some orosensory or postingestive factor(s).

Animals↗

[Assessment of vitamin B2, B6, and PP supply from data on excretion of vitamins and their metabolites in alimentary iron and riboflavin deficiency].

Alimentary deficiency in riboflavin and/or iron in rats involved distinct decrease in excretion of 4-pyridoxylic acid and 1-N-methyl nicotinamide--the metabolites considered as the indices of vitamins B6 and PP consumption. The effect observed appears to occur due to a decrease in activity of some iron- and flavin-containing enzymes participating in the metabolism of pyridoxine and niacin. Addition to the diet of the deficient component normalized these patterns. Use of the data on excretion of 4-pyridoxylic acid and 1-N-methyl nicotinamide as criteria of consumption of pyridoxine and niacin is discussed.

Animals↗

[Effect of pyridoxine on patterns of lipid metabolism in patients with alimentary obesity].

Studies of patients with alimentary-metabolic obesity, which were treated with pyridoxine and were maintained on a reduced diet, revealed a normalizing effect of the vitamin on some patterns of lipid metabolism. In patients, treated with pyridoxine, body weight, content of total lipids, cholesterol, phospholipids, glycerids and beta-lipoproteins in blood serum were decreased more distinctly as compared with patients, which were only maintained on a reduced diet. In hyperlipidaemia the positive effect of pyridoxine was more pronounced than in the cases with normal content of lipids in blood.

Body Weight↗

Fetal malnutrition--the price of upright posture?

The pattern of preterm fetal growth faltering, normally seen in man, differs from that observed in animals. This type of fetal growth cannot be considered as an adaptation to facilitate birth but is more likely to be due to rapid evolution and imperfect adaptation to the upright posture. The pattern of posture and physical activity during pregnancy may therefore be an important determinant of fetal growth. Differences in intrauterine nutrition existing between social groups, usually ascribed to variations of maternal diet and nutrition, may well result from different patterns of maternal activity in the weeks preceding birth.

Bed Rest↗

Dietary patterns and the risk of postmenopausal breast cancer.

The association between individual foods and breast cancer has been inconsistent. Therefore, we examined the association between diet and risk of postmenopausal breast cancer by the alternative approach of dietary patterns. Dietary patterns were identified with factor analysis from food consumption data collected from a food frequency questionnaire in 1984. Relative risks were computed using proportional hazard models and adjusted for known risk factors for breast cancer. Between 1984 and 2000, we ascertained 3,026 incident cases of postmenopausal breast cancer. We identified 2 major dietary patterns. The prudent pattern is characterized by higher intake of fruits, vegetables, whole grains, low-fat dairy products, fish and poultry, while the Western pattern is characterized by higher intake of red and processed meats, refined grains, sweets and desserts and high-fat dairy products. Neither of the patterns was associated with overall risk of postmenopausal breast cancer. However, a positive association between the Western pattern score was observed among smokers at baseline (relative risk = 1.44, comparing top to bottom quintiles; 95% CI = 1.02-2.03; p for trend = 0.03). An inverse association was observed between the prudent pattern and estrogen receptor-negative cancer (relative risk = 0.62; 95% CI = 0.45-0.88; p for trend = 0.006). Among the major food groups, higher consumptions of fruits (relative risk for 1 serving/day increase = 0.88; 95% CI = 0.80-0.97; p = 0.009) and vegetables (relative risk = 0.94; 95% CI = 0.88-0.99; p = 0.03) were significantly associated with decreased risk for ER(-) breast cancer. In conclusion, we did not observe an overall association between the prudent or Western pattern and overall breast cancer risk. However, a Western-type diet may elevate risk of breast cancer among smokers, and a prudent diet may protect against estrogen receptive-negative tumors.

Breast Neoplasms↗

Hunting income patterns among the Hadza: big game, common goods, foraging goals and the evolution of the human diet.

The assumption that large mammal hunting and scavenging are economically advantageous to hominid foragers is examined in the light of data collected among the Hadza of northern Tanzania. Hadza hunters disregard small prey in favour of larger forms (mean adult mass greater than or equal to 40 kg). Here we report experimental data showing that hunters would reduce their mean rates if they included small animals in the array they target. Still, daily variance in large animal hunting returns is high, and the risk of failure correspondingly great, significantly greater than that associated with small game hunting and trapping. Sharing large kills reduces the risk of meatless days for big game hunters, and obviates the problem of storing large amounts of meat. It may be unavoidable if large carcasses cannot be defended economically against the demands of other consumers. If so, then large prey are common goods. A hunter may gain no consumption advantage from his own big game acquisition efforts. We use Hadza data to model this 'collective action' problem, and find that an exclusive focus on large game with extensive sharing is not the optimal strategy for hunters concerned with maximizing their own chances of eating meat. Other explanations for the emergence and persistence of this practice must be considered.

Animals↗

Sucrase and lactase synthesis in suckling rat intestine in response to substrate administration.

The intestinal brush border disaccharidases separated by gel electrophoresis were studied after oral administration of a high sucrose or lactose diet to 11-day-old suckling rats during 3 days. Some modifications of the brush border protein and eyzyme patterns could be attributed to the effect of the basic diet: increase of glucoamylase, appearance of a weak sucrase activity and of a second molecular form of maltase. However, the specific action of a given disaccharide on the synthesis of the corresponding hydrolytic enzyme could be clearly demonstrated. Indeed, the electrophoretic pattern after sucrose or lactose feeding showed a marked increase of the protein bands corresponding to sucrase-isomaltase or lactase activities.

Administration, Oral↗

Changes in dietary patterns and certain nutrition-related diseases in urban and rural residents of Jiangsu Province, China, during the 1990s.

OBJECTIVE: To investigate into the changes of dietary patterns and their impacts on health of urban and rural residents in Jiangsu Province, China during the 1990s. METHODS: On the basis of the results of food consumption survey, the calorie intake was calculated according to the balanced diet method and the quality of diet was assessed by scores of desirable dietary pattern (DDP). RESULTS: It was found that food consumption and dietary patterns changed remarkably during the 1990s. Grain consumption was decreasing year by year, but the consumption of animal food was markedly increasing. Although the score of desirable dietary pattern (DDP) in urban residents was more than 90, the deducted score due to over-consumption of animal food increased. The mortality from infectious diseases evidently decreased in the whole province, while the death rates of some chronic diseases, such as diabetes, hypertension, colorectal cancer and breast cancer, were increasing rapidly in urban areas. CONCLUSIONS: Sufficient attention should be paid to the negative effects of change in dietary patterns on people's health, especially in the urban residents.

China↗