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ABSTRACT: The rate of APC mutations in the intestine increases in middle-age. At the same period of life, plant sterol and stanol enriched functional foods are introduced to diet to lower blood cholesterol. This study examined the effect of plant stanol enriched diet on intestinal adenoma formation in the Apc(Min) mouse. Apc(Min) mice were fed 0.8% plant stanol diet or control diet for nine weeks. Cholesterol, plant sterols and plant stanols were analyzed from the caecum content and the intestinal mucosa. Levels of β-catenin, cyclin D1, epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase 1/2 (ERK1/2) were measured from the intestinal mucosa by Western blotting. Gene expression was determined from the intestinal mucosa using Affymetrix and the data were analyzed for enriched categories and pathways. Plant stanols induced adenoma formation in the small intestine, however, the adenoma size was not affected. We saw increased levels of nuclear β-catenin, phosphorylated β-catenin (Ser675 and Ser552), nuclear cyclin D1, total and phosphorylated EGFR and phosphorylated ERK1/2 in the intestinal mucosa after plant stanol feeding. The Affymetrix data demonstrate that several enzymes of cholesterol synthesis pathway were up-regulated, although the cholesterol level in the intestinal mucosa was not altered. We show that plant stanols induce adenoma formation by activating Wnt and EGFR signaling. EGFR signaling seems to have promoted β-catenin phosphorylation and its translocation into the nucleus, where the expression of cyclin D1 was increased. Up-regulated cholesterol synthesis may partly explain the increased EGFR signaling in the plant stanol-fed mice.
The Journal of nutritional biochemistry 09/2012; · 4.29 Impact Factor
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ABSTRACT: Most clinical studies of probiotics use freeze-dried, powdered bacteria or bacteria packed in capsules. However, probiotics are commercially available in various food matrices, which may affect their persistence in the gastrointestinal tract. The objective of the study was to compare oral and faecal recovery during and after administration of a combination of Lactobacillus rhamnosus GG and LC705, Propionibacterium freudenreichii subsp. shermanii JS, and Bifidobacterium animalis subsp. lactis Bb12 as capsules, yoghurt, or cheese. This randomized, parallel-group, open-label trial (n=36) included a 4-week run-in, 2-week intervention, and 3-week follow-up period. Participants consumed 10(10)cfu/day of probiotic combination and provided saliva and faecal samples before, during, and after the intervention. Strain-specific real-time PCR was used to quantify the strains. L. rhamnosus GG was the only probiotic strain regularly recovered in saliva samples. During the intervention period it was recovered in the saliva of 88% of the volunteers at least once. No difference was found between the yoghurt and cheese groups. At the end of the intervention, L. rhamnosus GG and LC705 counts were high in faecal samples of all product groups (8.08 and 8.67log(10) genome copies/g, respectively). There was no matrix effect on strain quantity in faeces or the recovery time after ceasing the intervention. For P. freudenreichii subsp. shermanii JS and B. animalis subsp. lactis Bb12, a matrix effect was found at the end of the intervention (P<0.01 and P<0.001, respectively) and in the recovery time during follow-up (P<0.05 for both). Yoghurt yielded the highest faecal quantity of JS and Bb12 strains (8.01 and 9.89log(10) genome copies/g, respectively). The results showed that the administration matrix did not influence the faecal quantity of lactobacilli, but affected faecal counts of propionibacteria and bifidobacteria that were lower when consumed in cheese. Thus, the consumption of probiotics in yoghurt matrix is highly suitable for studying potential health benefits and capsules provide a comparable means of administration when the viability of the strain in the capsule product is confirmed.
International journal of food microbiology 10/2010; 144(2):293-300. · 3.01 Impact Factor
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ABSTRACT: Green leafy vegetables contain a wealth of potential chemopreventive compounds. Chlorophyll and its derivatives can trap aflatoxin
and other mutagens by complex formation and appear protective against carcinogens in various animal and human models. They
also have antioxidative and immunomodulatory properties. Folate is essential in DNA synthesis and methylation, and is required
especially by rapidly proliferating tissues. For cancer prevention, dietary folate may be preferable to the much more stable
folic acid used in fortification. Of the various green vegetables, spinach and perilla have been widely studied. Spinach has
high antioxidant content, and its glycolipid fractions inhibit cancer cell proliferation and suppress tumours in murine models.
Luteolin, rosmarinic acid and triterpenes extracted from perilla leaves are potent antitumourigenic and anti-inflammatory
agents.
KeywordsSpinach-Perilla-Chlorophyll-Folate-Luteolin-Rosmarinic acid-Triterpenes-Chemoprevention
06/2010: pages 31-45;
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Marianne Hauge Wennersberg,
Annika Smedman,
Anu M Turpeinen,
Kjetil Retterstøl,
Siv Tengblad,
Endla Lipre,
Antti Aro,
Pertti Mutanen,
Ingebjørg Seljeflot,
Samar Basu,
Jan I Pedersen, Marja Mutanen,
Bengt Vessby
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ABSTRACT: Some epidemiologic studies have suggested inverse relations between intake of dairy products and components of the metabolic syndrome.
The objective was to investigate the effects of an increased intake of dairy products in persons with a habitually low intake on body composition and factors related to the metabolic syndrome.
Middle-aged overweight subjects (n = 121) with traits of the metabolic syndrome were recruited in Finland, Norway, and Sweden and randomly assigned into milk or control groups. The milk group was instructed to consume 3-5 portions of dairy products daily. The control group maintained their habitual diet. Clinical investigations were conducted on admission and after 6 mo.
There were no significant differences between changes in body weight or body composition, blood pressure, markers of inflammation, endothelial function, adiponectin, or oxidative stress in the milk and the control groups. There was a modest unfavorable increase in serum cholesterol concentrations in the milk group (P = 0.043). Among participants with a low calcium intake at baseline (<700 mg/d), there was a significant treatment effect for waist circumference (P = 0.003) and sagittal abdominal diameter (P = 0.034). When the sexes were analyzed separately, leptin increased (P = 0.045) and vascular cell adhesion molecule-1 decreased (P = 0.001) in women in the milk group.
This study gives no clear support to the hypothesis that a moderately increased intake of dairy products beneficially affects aspects of the metabolic syndrome. The apparently positive effects on waist circumference and sagittal abdominal diameter in subjects with a low calcium intake suggest a possible threshold in relation to effects on body composition.
American Journal of Clinical Nutrition 09/2009; 90(4):960-8. · 6.67 Impact Factor
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ABSTRACT: The initial purpose of this study was to assess the role of estrogen receptor beta (ERbeta) in intestinal tumorigenesis by examining the effects of an ERbeta knockout (ERbeta(-/-)) on Apc(Min) mice. In order to accomplish this goal on a uniform genetic background, we were required to backcross the ERbeta knockout from the 129P2 genetic background to the B6 genetic background for 10 generations. Midway through this process, we performed a test cross in which mice from the N(5) backcross generation of the ERbeta knockout strain were intercrossed with Apc(Min/+) mice to obtain Apc(Min/+) ERbeta(+/+), Apc(Min/+) ERbeta(+/-) and Apc(Min/+) ERbeta(-/-) mice. Intestinal tumorigenesis in the N(5)F(2) mice was evaluated at 14 weeks of age. The analysis of the impact of ERbeta in the N(5) cross was complicated by segregating 129P2-derived alleles that affected tumor number and were unlinked to ERbeta. Genetic linkage analysis of this cross permitted the localization of a single genetic modifier of tumor number in Apc(Min/+) mice. This locus, Modifier of Min 5 (Mom5), maps to proximal mouse chromosome 5; the 129P2 allele of this locus is associated with a 50% reduction in mean intestinal tumor number. Through in silico analysis and confirmatory sequencing, we have identified the Rad50-interacting protein-1 gene as a strong candidate for Mom5.
Carcinogenesis 08/2009; 30(9):1591-6. · 5.70 Impact Factor
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Alicia G Cleveland,
Seija I Oikarinen,
Kimberly K Bynoté,
Maija Marttinen,
Joseph J Rafter,
Jan-Ake Gustafsson,
Shyamal K Roy,
Henry C Pitot,
Kenneth S Korach,
Dennis B Lubahn, Marja Mutanen,
Karen A Gould
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ABSTRACT: Estrogen receptors (ERs) [ERalpha (Esr1) and ERbeta (Esr2)] are expressed in the human colon, but during the multistep process of colorectal carcinogenesis, expression of both ERalpha and ERbeta is lost, suggesting that loss of ER function might promote colorectal carcinogenesis. Through crosses between an ERalpha knockout and Apc(Min) mouse strains, we demonstrate that ERalpha deficiency is associated with a significant increase in intestinal tumor multiplicity, size and burden in Apc(Min/+) mice. Within the normal intestinal epithelium of Apc(Min/+) mice, ERalpha deficiency is associated with an accumulation of nuclear beta-catenin, an indicator of activation of the Wnt-beta-catenin-signaling pathway, which is known to play a critical role in intestinal cancers. Consistent with the hypothesis that ERalpha deficiency is associated with activation of Wnt-beta-catenin signaling, ERalpha deficiency in the intestinal epithelium of Apc(Min/+) mice also correlated with increased expression of Wnt-beta-catenin target genes. Through crosses between an ERbeta knockout and Apc(Min) mouse strains, we observed some evidence that ERbeta deficiency is associated with an increased incidence of colon tumors in Apc(Min/+) mice. This effect of ERbeta deficiency does not involve modulation of Wnt-beta-catenin signaling. Our studies suggest that ERalpha and ERbeta signaling modulate colorectal carcinogenesis, and ERalpha does so, at least in part, by regulating the activity of the Wnt-beta-catenin pathway.
Carcinogenesis 07/2009; 30(9):1581-90. · 5.70 Impact Factor
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ABSTRACT: Over the past few years, evidence has accumulated indicating that apart from genetic alterations, epigenetic alterations, through e.g. aberrant promoter methylation, play a major role in the initiation and progression of colorectal cancer (CRC). Even in the hereditary colon cancer syndromes, in which the susceptibility is inherited dominantly, cancer develops only as the result of the progressive accumulation of genetic and epigenetic alterations. Diet can both prevent and induce colon carcinogenesis, for instance, through epigenetic changes, which regulate the homeostasis of the intestinal mucosa. Food-derived compounds are constantly present in the intestine and may shift cellular balance toward harmful outcomes, such as increased susceptibility to mutations. There is strong evidence that a major component of cancer risk may involve epigenetic changes in normal cells that increase the probability of cancer after genetic mutation. The recognition of epigenetic changes as a driving force in colorectal neoplasia would open new areas of research in disease epidemiology, risk assessment, and treatment, especially in mutation carriers who already have an inherited predisposition to cancer.
World Journal of Gastroenterology 02/2009; 15(3):257-63. · 2.47 Impact Factor
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ABSTRACT: The aim of this study was to examine the effect of the administration of Lactobacillus rhamnosus strain LC705 and Propionibacterium freudenreichii ssp shermanii strain JS in capsules on serum cholesterol and triglyceride levels in mildly or moderately hypercholesterolemic men.
Thirty-eight basically healthy men, mean age 42 years (range 24-55), mean cholesterol 6.2 mmol/L (5.3-8.2 mmol/L), participated in this double-blind, randomised, placebo-controlled, two-period crossover study with 4-week treatment periods. The subjects consumed daily two probiotic capsules containing viable Lactobacillus rhamnosus LC705 and Propionibacterium freudenreichii ssp shermanii JS (2 x 10(10) colony forming units of each strain daily) or two placebo capsules. Serum lipids were assessed before the intervention, at the end of both 4-week treatment periods, and 2 weeks after the second treatment period. Dietary and lifestyle habits were carefully monitored.
All the subjects completed the study, and the probiotic capsules were well tolerated. Dietary habits and the intake of energy and nutrients, such as saturated fatty acids and cholesterol, did not differ between the treatment groups. No changes in total cholesterol, HDL cholesterol, LDL cholesterol or triglyceride levels were observed during the consumption of the probiotics compared to placebo.
The administration of Lactobacillus rhamnosus LC705 and Propionibacterium freudenreichii ssp shermanii JS did not affect serum lipids.
Journal of the American College of Nutrition 09/2008; 27(4):441-7. · 2.29 Impact Factor
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ABSTRACT: The mechanism that drives the growth of some colonic adenomas towards malignancy, while permitting others to remain for decades in quiescence, remains unknown. Diets can alter the growth rate of intestinal tumours but it is still unknown whether diets are able to alter the molecular biology of these adenomas in a way that predicts further outcome. To address this issue we fed Min/+ mice with two diets known to lead to different adenoma outcomes: a high-fat control diet (n 15) or a high-fat inulin-enriched (10 % w/w) diet (n 13). To study the effect of diet on cell signalling during adenoma growth, the adenomas of each Min/+ mouse were divided into three size-categories, and the levels of beta-catenin, E-cadherin, cyclin D1 and matrix metalloproteinase-9, which are known to be involved in colon tumorigenesis, were determined. The growth-promoting inulin diet resulted in more large adenomas than the control feeding (P = 0.003) and doubled the total area of the adenomas (P = 0.008). The inulin diet increased the expression of nuclear beta-catenin (P = 0.004) and its target cyclin D1 (P = 0.017) as the adenomas increased in size from small to large, indicating the presence of an accelerated cancerous process. Neither phenomenon was seen in the control group during adenoma growth. Our results suggest that in addition to the number, size, and growth rate of adenomatous polyps, the signalling pattern of the adenomas should also be considered when evaluating preventive dietary strategies.
British Journal Of Nutrition 06/2008; 99(5):963-70. · 3.01 Impact Factor
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ABSTRACT: Berries are a good natural source of phenolic compounds and many berries or their compounds have been shown to be chemopreventive. White currant is an interesting berry, as it contains low levels of dominant berry phenolics such as ellagic acid, anthocyanins and other flavonoids.
To study if white currant is chemopreventive in an experimental model for intestinal tumorigenesis and further study the effects on beta-catenin and NF-kappaB signaling pathways.
Multiple intestinal neoplasia (Min) mice were fed an AIN-93G based control diet or a diet containing 10% freeze dried white currant (Ribes x pallidum) for 10 weeks. Cell signaling parameters were analysed from intestinal adenomas and surrounding mucosa by Western blotting and immunohistochemistry.
The white currant diet reduced the number of adenomas from 81 (min-max 47-114) to 51 (36-84) in the total small intestine of Min mice (P<0.02). Most of the adenomas develop in the distal part of the small intestine, and in this area white currant reduced the number from 49 to 29.5 (P<0.01) and also the size of the adenomas from 0.88 mm to 0.70 mm (P<0.02). In the colon white currant increased the number of adenomas (0.3+/-0.6 vs. 0.8+/-0.6, mean +/- SD, P<0.05), but did not affect the size. White currant reduced nuclear beta-catenin and NF-kappaB protein levels in the adenomas (P<0.05 and P<0.02, respectively). They were correlated with the size of adenomas (P<0.01).
This study shows that white currant is effective in preventing cancer initiation and progression in the Min mouse. Whether the positive effects are due to its special phenolic composition needs to be studied in more detail.
European Journal of Nutrition 04/2008; 47(3):115-22. · 2.75 Impact Factor
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ABSTRACT: Berries contain a number of compounds that are proposed to have anticarcinogenic properties. We wanted to see if pure ellagic acid, natural ellagitannins and three wild berries have any effect on the adenoma formation in Apc- mutated Min/+ mice. Min/+ mice were fed high-fat AIN93-G diets containing 10% (w/w) freeze-dried bilberry (Vaccinium myrtillus), lingonberry (Vaccinium vitis-idaea), cloudberry (Rubus chamaemorus), cloudberry seeds or cloudberry pulp or pure ellagic acid at 1564 mg/kg for 10 weeks. beta-Catenin and cyclin D1 protein levels in the adenomas and in the normal-appearing mucosa were determined by Western blotting and immunohistochemistry. Early changes in gene expression in the normal-appearing mucosa were analyzed by Affymetrix microarrays. Three wild berries significantly reduced tumour number (15-30%, p < 0.05), and cloudberry and lingonberry also reduced tumour size by over 60% (p < 0.01). Cloudberry resulted in decreased levels of nuclear beta-catenin and cyclin D1 and lingonberry in the level of cyclin D1 in the large adenomas (p < 0.05). Affymetrix microarrays revealed changes in genes implicated in colon carcinogenesis, including the decreased expression of the adenosine deaminase, ecto-5f-nucleotidase and PGE2 receptor subtype EP4. Ellagic acid had no effect on the number or size of adenomas in the distal or total small intestine but it increased adenoma size in the duodenum when compared with the control diet (p < 0.05). Neither cloudberry seed nor pulp had any effect on the adenoma formation. Berries seem to have great potential as a source of chemopreventive components.
Asia Pacific Journal of Clinical Nutrition 01/2008; 17 Suppl 1:123-5. · 1.13 Impact Factor
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ABSTRACT: Berries contain a number of compounds that are proposed to have anticarcinogenic properties. We studied the effects and molecular mechanisms of wild berries with different phenolic profiles on intestinal tumorigenesis in multiple intestinal neoplasia/+ mice. The mice were fed a high-fat AIN93-G diet (Con) or AIN93-G diets containing 10% (w:w) freeze-dried bilberry, lingonberry (LB), or cloudberry (CB) for 10 wk. All 3 berries significantly inhibited the formation of intestinal adenomas as indicated by a 15-30% reduction in tumor number (P < 0.05). CB and LB also reduced tumor burden by over 60% (P < 0.05). Compared to Con, CB and LB resulted in a larger (P < 0.05) proportion of small adenomas (43, 69, and 64%, respectively) and a smaller proportion of large adenomas (56, 29, and 33%, respectively). Beta-catenin and cyclin D1 in the small and large adenomas and in the normal-appearing mucosa were measured by Western blotting and immunohistochemistry. CB resulted in decreased levels of nuclear beta-catenin and cyclin D1 and LB in the level of cyclin D1 in the large adenomas (P < 0.05). Early changes in gene expression in the normal-appearing mucosa were analyzed by Affymetrix microarrays, which revealed changes in genes implicated in colon carcinogenesis, including the decreased expression of the adenosine deaminase, ecto-5'-nucleotidase, and prostaglandin E2 receptor subtype EP4. Our results indicate that berries are potentially a rich source of chemopreventive components.
Journal of Nutrition 11/2007; 137(10):2285-90. · 3.92 Impact Factor
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ABSTRACT: The lignans matairesinol (MAT) and secoisolariciresinol (SECO) were fed to Min mice at 0.02% (w/w) in diet to study their effects on intestinal tumor development. The mean number (67 vs. 51, P=0.052) and size (1.4 vs. 1.2 mm, P=0.011) of tumors in the MAT group was elevated when compared with the control group. Tumor formation of the SECO group did not differ from the control group. Intake of MAT increased the level of both MAT and enterolactone in the plasma while SECO feeding increased SECO, enterodiol, and enterolactone (P=0.001). These results showed that MAT or SECO do not prevent intestinal carcinogenesis in Min mice and that MAT may have adverse effects.
Cancer Letters 03/2006; 233(2):309-14. · 4.24 Impact Factor
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ABSTRACT: In vitro fermentation models have been used widely for studies of shortchain fatty acid (SCFA) formation from carbohydrates, whereas the suitability of these methods for enterolactone (ENL) formation has received less attention.
The aim was to study the suitability of an in vitro fermentation model for prediction of bioconversion of lignans to ENL, to compare the approach with that of an in vivo rat model and to study the SCFA formation in both models.
Predigested samples of rye bran (R), flaxseed meal (F) alone, or in combination with rye bran (R&F) and a faecal control were incubated in an in vitro fermentation model using human faecal microbiota. In the in vivo experiment rats consumed a non-fibre control diet (C) or diets supplemented either with rye bran (R), flaxseed meal (F) alone, or with their combination (R&F) for four weeks. Enterodiol (END), ENL and SCFA concentrations were measured from in vitro faecal fermentation samples and from the intestinal contents of rats. Plasma ENL concentrations from rats were also measured.
The highest ENL production was found in vitro with the F supplement (areas under curve: 740 +/- 4, 7,500 +/- 400, 2,600 +/- 500 and 1,520 +/- 70 nmol x h for the R, F, R&F supplements and faecal control, respectively). In vivo, the concentration of ENL in caecal digesta from flaxseed meal was significantly (P < 0.05) enhanced by the presence of rye bran (medians 261, 407 and 24 nmol/g in the F, R&F and C groups, respectively). No correlation was found between the models regarding ENL production, possibly due to different responses to the presence of rye bran matrix, differences in microbiota or application of a batch in the in vitro fermentation model. Rye bran supplementation enhanced butyrate production both in vitro and in vivo.
In vitro fermentation and the in vivo rat models responded differently to the presence of rye bran and no correlation with regard to the ENL formation from flaxseed lignans was observed.
European Journal of Nutrition 02/2006; 45(1):45-51. · 2.75 Impact Factor
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ABSTRACT: Ellagic acid has been shown to have chemopreventive effects in various experimental cancer models. We wanted to see whether pure ellagic acid and natural ellagitannins from cloudberry (Rubus chamaemorus) seed and pulp have any effect on adenoma formation in Apc-mutated Min mice. From the age of 5 wk, the mice were fed either a control diet, a diet containing pure ellagic acid at 1,564 mg/kg, or diets containing 4.7% (wt/wt) cloudberry seeds or 5.3% cloudberry pulp. The concentrations of ellagitannins and free ellagic acid in the seed diet were 807 and 42 mg/kg and in the pulp diet 820 and 34 mg/kg, respectively. After the 10-wk feeding period, ellagic acid had no effect on the number or size of adenomas in the distal or total small intestine, but it increased adenoma size in the duodenum when compared with the control diet (1.50+/-0.29 vs. 1.16+/-0.31 mm; P=0.029). Neither cloudberry seed nor pulp diets had any effect on the adenoma formation. Chemopreventive effects and mechanisms of whole cloudberry and other similar sources of phenolic compounds should, however, be studied, further taking into account food matrix and interactions with other dietary constituents that may be involved in the bioavailability and metabolism of ellagitannins.
Nutrition and Cancer 02/2006; 54(1):79-83. · 2.78 Impact Factor
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ABSTRACT: The nuclear factor kappaB signaling pathway has gained attention for its role in the carcinogenic process. We have measured the protein levels of the p65 subunit during a growth of adenomas in the Min mouse model for colon cancer. To study how an accelerated growth of adenomas affect cell signalling, adenoma growth was increased by an inulin diet (10%) that we have shown previously to be a promotor of adenoma formation. In our study, the association between NF-kappaB, p53, beta-catenin, Fas and COX-2 were evaluated by measuring their protein levels in 9- and 15-week old Min mouse adenomas and surrounding mucosa. The amount of p65 rouse between 9- and 15-weeks in the mucosa of the control-fed mice (p = 0.032). The inulin-fed mice had less p65 in the nucleus of the mucosa at 15 weeks of age compared to the control (p = 0.064), although the adenomas were significantly larger (1.46 mm +/- 0.12 for inulin, 0.97 mm +/- 0.12 for control, p < 0.001). Nuclear p65 correlated positively with nuclear p53 in the mucosa (p < 0.001) and adenoma (p < 0.001) tissues. Also, p65 correlated positively with nuclear beta-catenin in the mucosa (p = 0.012) and the adenoma (p = 0.001). Fas expression increased in the inulin group between 9-15 weeks (p = 0.034) and correlated negatively with p65 (p = 0.03). The amount of COX-2 in the adenoma tissue increased between 9-15 weeks and did not correlate with p65. The results suggest that p65 is involved in a p53-dependent apoptotic response in the Min mouse.
International Journal of Cancer 02/2006; 118(2):279-83. · 5.44 Impact Factor
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ABSTRACT: Flaxseed is a dietary source of possible chemopreventive compounds such as lignans and alpha-linolenic acid (ALA). To study the effects of a flaxseed mixture on adenoma formation in multiple intestinal neoplasia mice, the mice were fed a diet containing 2.7 % flaxseed, 4.5 % fibre and 3.7 % ALA. To elucidate the effect of oils of the mixture we also composed a diet without flaxseed but with the same oil composition. The median number of adenomas in the small intestine was fifty-four for the control group, and thirty-seven (P=0.023) and forty-two (P=0.095) for flaxseed and oil groups, respectively. Compared with controls (1.2 mm), the adenoma size was smaller in the flaxseed (0.9 mm; P=0.002) and oil (1.0 mm; P=0.012) groups. Both diets changed the proportions of n-3 and n-6 fatty acids in the colonic mucosa. Membrane beta-catenin and protein kinase C (PKC)-zeta levels were reduced in the adenoma v. mucosa (P<0.05), and an inverse association was found between the membrane PKC-zeta in the mucosa and the adenoma number (r -0.460, P=0.008, n 32). Only the flaxseed diet increased lignan levels in the caecum (P=0.002) and in plasma (P=0.002) but they were not associated with tumour formation. The results suggest that the preventive effect of flaxseed on colon carcinogenesis may be due to the oil part of flaxseed, and the loss of beta-catenin and PKC-zeta from the membranes of the mucosal tissue may play a permissive role in intestinal tumour development.
British Journal Of Nutrition 10/2005; 94(4):510-8. · 3.01 Impact Factor
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ABSTRACT: We have earlier shown that dietary fructo-oligosaccharide inulin enhances adenoma growth in multiple intestinal neoplasia (Min/+) mice. To further explore inulin-induced early biochemical changes in the normal-appearing mucosa, Min/+ mice were fed from the age of 5 weeks to the ages of 8 and 15 weeks a control diet or an inulin-enriched diet (10% w/w). In addition, the wild-type littermates were fed with the same diets until the age of 8 weeks, in order to determine whether similar changes happen both in the wild-type and Min/+ mice. The mucosa without adenomas was collected and fractionated to nuclear, cytosolic and membrane pools. The protein levels of beta-catenin, cyclin D1 and E-cadherin were determined by Western blotting at both time points, and immunohistochemical stainings were done for 8-week-old mice. The promotion of adenoma growth by inulin (week 15, 1.3-fold increase, P=.0004) was associated with accumulation of cytosolic and nuclear beta-catenin, and increased amount of cytosolic cyclin D1 (1.5-fold increase, P=.003) in the normal-appearing mucosa of the Min/+ mice. Furthermore, inulin feeding reduced the membranous pools of beta-catenin and E-cadherin. Also in the wild-type mice the drop in membranous beta-catenin was clear (P=.015), and, moreover, a subset of crypts had enhanced nuclear beta-catenin staining. These data indicate that dietary inulin can already activate in the normal-appearing mucosa beta-catenin signaling, which in the presence of Apc mutation induces adenoma growth and even in the wild-type mice direction of the changes is similar.
The Journal of Nutritional Biochemistry 08/2005; 16(7):402-9. · 3.89 Impact Factor
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ABSTRACT: Recently the increasing prevalence of gastrointestinal diseases, including neoplasm, has resulted in the necessity of characterising not only the tumours, but also healthy mucosa. Research into the morphological changes of healthy mucosa under different experimental conditions, including drugs, special diets and the use of probiotic bacteria, is greatly facilitated by the availability of animal models. In spite of the widespread use of mice in gastrointestinal research, there is a lack of information on the qualitative and quantitative histological characteristics of the intestinal mucosa of the mouse. The aim of this study was to assess the morphological characteristics and the postnatal development of the small intestine of wild type mice -- C57BL/6J. The mice were aged either 5 weeks or 12 weeks. The 12-week-old mice had been weaned at the age of 5 weeks. After dissection the small intestine was divided into 5 equal portions and randomly chosen microscopical sections from each were stained with haematoxylin and eosin. The parameters describing the morphology of the small intestine (villus height, depth of the crypt, villus width near the crypt, width of the villus connective tissue near the crypt, thickness of the muscular layer and the height of the enterocytes and their nuclei) were evaluated under a light microscope. In both age groups the height and width of the villi decreased, while the thickness of the muscular layer increased in the distal direction. The height of the enterocytes decreased and the height of the enterocyte nucleus increased towards the colon in both age groups. The depth of the crypts was greater in the younger animals than in the older ones. Our data provides the baseline morphological description of the small intestinal mucosa in wild type mice, strain C57BL/6J, which can be used as a reference for testing the influence of drugs, toxins, nutrients and inborn mutations on the mouse intestine.
Folia morphologica 12/2004; 63(4):423-30. · 0.52 Impact Factor
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ABSTRACT: High intake of vegetables and fruits is associated with decreased risk of coronary heart disease. Part of these cardioprotective effects may be mediated via the antithrombotic effects of compounds found in vegetables and fruits, such as flavonoids.
To study the effects of high and low intake of vegetables, berries and apple on platelet function and inflammatory markers.
The study was a randomised, controlled parallel human dietary intervention with healthy female and male volunteers (n = 77, 19-52 y). Nineteen healthy volunteers served as controls. The volunteers consumed one of four strictly controlled isocaloric 6-week diets containing either 810 or 196 g/10 MJ of vegetables, berries and apple and rich either in linoleic acid (11% of energy, en%) or oleic acid (12 en%). Blood and three 24-hour urine samples were collected at the beginning and at the end of the study period for analyses of various markers of platelet function and inflammation.
No differences between the treatment groups were seen in platelet count or volume, markers of platelet activation ( ex vivo aggregation to ADP and thrombin receptor activating peptide, protein kinase C activity, urinary 2,3-dinor-thromboxane B2 excretion, plasma P-selectin), plasma intercellular adhesion molecule-1, sensitive C-reactive protein, or antiphospholipid antibodies.
The results indicate that in healthy volunteers 6-week diets differing markedly in the amounts of vegetables, berries and apple do not differ in their effects on platelets or inflammation.
European Journal of Nutrition 07/2004; 43(3):175-82. · 2.75 Impact Factor
