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M Mutanen

Publications and source records attributed to M Mutanen.

At least 19 recordsLinked to original sources
PubMed2004

No effect on adenoma formation in Min mice after moderate amount of flaxseed.

BACKGROUND & AIM: The mammalian lignan enterolactone (ENL) produced from plant lignans, e. g. secoisolariciresinol diglycoside (SDG), may protect against various cancers in humans. The present work aims to evaluate the effect of flaxseed on tumour formation in multiple intestinal neoplasia (Min) mice, a model for colon tumorigenesis. DESIGN: Male and female Min mice were fed either with a non-fibre control diet or the same diet supplemented with 0.5 % (w/w) defatted flaxseed meal. Conversion of SDG to the mammalian lignans enterodiol (END) and ENL in the gut, and plasma ENL, were measured by HPLC with coulometric electrode array detector (CEAD) and timeresolved fluoroimmunoassay, respectively. Wild-type mice were also fed with the experimental diets in order to see whether lignan metabolism is different in Min and wild-type mice. RESULTS: The total number of adenomas or their size in the small intestine was not different in the flaxseed and control groups. The flaxseed group had a tendency for a decreased number of colon adenomas in both genders. Gender and genotype based differences were found in the intestinal ENL levels. When compared to Min females, Min males in the flaxseed group had several fold higher ENL levels in the small intestine (Min males 125 +/- 124.5 nmol/g vs. females 22.8 +/- 16.0 nmol/g, P = 0.048) and caecum (47.6 +/- 31.6 nmol/g vs. females 14.5 +/- 6.6 nmol/g, P = 0.001). Presence of adenomas in the gut influences the intestinal lignan metabolism. Min mice had less intestinal END and ENL as compared with the wild-type mice (P < 0.05). Mean plasma ENL increased 7-fold during the flaxseed feeding (7 nmol/L in control vs. 50 nmol/L in flaxseed group) but no differences between gender and genotype were found. The plasma ENL level did not correlate with adenoma number in the small intestine and colon. CONCLUSION: The number of intestinal adenomas in the Min mouse model is not related to ENL level in plasma nor is it associated with the levels of intestinal lignans. A gender difference in ENL lignan metabolism was found in the gut but not in the plasma.

Adenoma↗
PubMed2003

Plasma enterolactone or intestinal Bifidobacterium levels do not explain adenoma formation in multiple intestinal neoplasia (Min) mice fed with two different types of rye-bran fractions.

The study was designed to evaluate whether two types of rye-bran fractions result in distinct bifidogenic effect or enterolactone production in multiple intestinal neoplasia (Min) mice and whether these parameters are associated with intestinal tumorigenesis in this animal model. The experimental diets were a non-fibre diet (control), a rye-bran diet, and diets containing either the soluble extract or the insoluble fraction prepared from rye bran. The main result on adenoma formation in these experiments was the observation that the soluble extract increased number (P=0.012) and size (P=0.008) of adenomas in the distal small intestine when compared with the non-fibre group. All rye-supplemented diets supported similarly the in vivo growth of Bifidobacterium (10(8)-10(9) colony forming units/g) in Min mice, whereas the non-fibre diet lowered intestinal Bifidobacterium below the level of detection. The results show that water solubility does not affect the bifidogenicity of rye bran. Mean plasma enterolactone concentration was highest in the rye-bran group (30.0 nmol/l; P=0.002), which along with the soluble-extract group (16.2 nmol/l; P=0.024) differed significantly from the non-fibre diet group (7.5 nmol/l). Thus, the mice fed with the rye bran were the best enterolactone producers. In conclusion, rye bran and rye fractions influence adenoma formation in Min mice to a varying degree but plasma enterolactone levels or the production of bifidogenic bacteria do not mediate the effect.

4-Butyrolactone↗
PubMed2001

High linoleic acid, low vegetable, and high oleic acid, high vegetable diets affect platelet activation similarly in healthy women and men.

Upregulation of protein kinase C (PKC), an important enzyme in platelet activation, could be one step toward platelet hyperactivity. PKC activation can be modulated by dietary components in vitro, but few data are available concerning the in vivo effects. In this strictly controlled human dietary intervention, the influence of dietary unsaturated fatty acids and vegetable compounds on platelet activation was investigated. A high linoleic acid diet (10% of energy) with small amounts of vegetables (no berries or apples) was consumed by 9 women and 4 men (24.1 +/- 3.9 y), and was compared with a high oleic acid diet (12% of energy) with considerable amounts of vegetables, berries and apples consumed by 8 women and 4 men (24.2 +/- 5.5 y). Subjects were healthy Finnish volunteers. Compliance with the experimental protocol was good, as indicated by changes in plasma fatty acids and concentrations of vitamin C, beta-carotene and alpha-tocopherol. No differences between groups were seen in indices of platelet activation, including platelet aggregation, total PKC activity and distribution of PKC isoenzymes alpha, beta(II) and delta. The results indicate that in apparently healthy and fairly young subjects with adequate vitamin intakes, diets differing markedly in their amounts of linoleic and oleic acids, and vegetables, berries and apples do not differ in platelet activation.

Antioxidants↗
PubMed2001

Fats, lipids and blood coagulation.

Saturated and n-3 fatty acids, postprandial lipaemia, and the combined effects of fatty acids and lipid-lowering drugs have been of principal interest in recent studies in the field of dietary fats, lipids and haemostasis. The sex-specific effect of individual saturated fatty acids on coagulation factor VII activity has been discovered, and the significant effect of factor VII R353Q polymorphism on the postprandial response has also been found. An increased intake of n-3 fatty acids or fat reduction when combined with intensive lifestyle interventions may lead to reduced thrombotic potential in type 2 diabetic patients and obese individuals. Furthermore, positive effects on haemostasis by combined treatment with long-chain n-3 fatty acids and simvastatin indicate that n-3 fatty acids may be of some relevance with lipid-lowering drugs. The possible unfavourable effect of n-3 fatty acids on plasminogen activator inhibitor-1 activity is still a matter of dispute, but recent studies suggest that n-3 fatty acids, including alpha-linolenic acid, may have antithrombotic effects by enhancing protein C activity.

Blood Coagulation↗
PubMed2000

Chemopreventive activity of crude hydroxsymatairesinol (HMR) extract in Apc(Min) mice.

We studied the effects of a lignan, hydroxymatairesinol (HMR), and rye bran on intestinal tumor development in adenomatous polyposis colimultiple intestinal neoplasia (Apc)(Min) mice. HMR showed a strong chemopreventive effect in this animal model. The mean number of adenomas in the small intestine was significantly lower (26. 6+/-11.0, P<0.05) in mice fed the inulin and HMR when compared with the inulin and inulin/rye bran fed mice (39.6+/-8.9 and 36.0+/-7.4, respectively). HMR resulted in normalization of beta-catenin levels in adenoma tissue, indicating that HMR mediates its chemopreventive effect through the Apc-beta-catenin pathway. In the cytosolic fraction, beta-catenin level in adenoma tissue was significantly elevated (P=0.008-0.013) in all the diet groups as compared with that of the surrounding mucosa. In the nuclear fraction, beta-catenin in the inulin (3.15+/-2.9 relative units) and inulin/rye (5.17+/-6.94 relative units) groups was also significantly higher (P=0.003-0.009) in the adenoma tissue when compared with the surrounding mucosa (0.5+/-0.5 and 0.35+/-0.39 relative units). However, HMR was able to restore nuclear beta-catenin level of the adenoma tissue (0.41+/-0.25 relative units) to the level found in the surrounding mucosa (0.36+/-0.28 relative units).

Adenoma↗
PubMed2000

Chemopreventative activity of crude hydroxymatairesinol (HMR) extract in Apc(Min) mice [corrected].

We studied the effects of a lignan, hydroxymatairesinol (HMR), and rye bran on intestinal tumor development in adenomatous polyposis colimultiple intestinal neoplasia (Apc)(Min) mice. HMR showed a strong chemopreventive effect in this animal model. The mean number of adenomas in the small intestine was significantly lower (26.6+/-11.0, P<0.05) in mice fed the TNS tumor promoter insulin and HMR when compared with the insulin and insulin/rye bran fed mice (39.6+/-8.9 and 36.0+/-7.4, respectively). HMR resulted in normalization of beta-catenin levels in adenoma tissue, indicating that HMR mediates its chemopreventive effect through the Apc-beta-catenin pathway. In the cytosolic fraction, beta-catenin level in adenoma tissue was significantly elevated (P=0.008-0.013) in all the diet groups as compared with that of the surrounding mucosa. In the nuclear fraction, beta-catenin in the insulin (3.15+/-2.9 relative units) and insulin/rye (5.17+/-6.94 relative units) groups was also significantly higher (P=0.003-0.009) in the adenoma tissue when compared with the surrounding mucosa (0.5+/-0.5 and 0.35+/-0.39 relative units). However, HMR was able to restore nuclear beta-catenin level of the adenoma tissue (0.41+/-0.25 relative units) to the level found in the surrounding mucosa (0.36+/-0.28 relative units).

Adenomatous Polyposis Coli↗
PubMed2000

Lipid peroxidation status, somatic mutations and micronuclei in peripheral lymphocytes: a case observation on a possible interrelationship.

A controlled dietary study was conducted in healthy female volunteers and reported elsewhere [1]. In a subset of samples four different biomarkers were analyzed: plasma malondialdehyde (MDA) levels and urinary 8-isoprostaglandin-F(2alpha) were measured as markers for lipid peroxidation. The frequency of hprt (hypoxanthine guanine phosphoribosyl transferase) mutants and micronuclei in peripheral blood lymphocytes were analyzed as indicators of genotoxic effects. One of the ten individuals showed extremely high background levels in all of the four endpoints measured. This case observation raises the possibility that life style factors and dietary habits affect the level of DNA reactive lipid peroxidation products, which in turn increase mutagenic and cytogenetic effects. A possible association between these biomarkers, particularly in relation to dietary fat intake and antioxidant status, should now be studied in a larger trial.

Adult↗
PubMed2000

A high-beef diet alters protein kinase C isozyme expression in rat colonic mucosa.

We recently reported that a red meat (beef) diet relative to a casein-based diet increases protein kinase C (PKC) activity in rat colonic mucosa. The purpose of this study was to further elucidate the effects of a high-beef diet on colonic intracellular signal transduction by analyzing steady-state protein levels of different PKC isozymes as well as activities of the three types of sphingomyelinases. Male Wistar rats (n = 12/group) were fed AIN93G-based diets either high in beef or casein for 4 weeks. Rats fed the beef diet had significantly (P < 0.05) higher cytosolic PKC alpha and lower membrane PKC delta protein levels than rats fed the casein diet. The beef-fed rats also had alterations in subfractions of PKC zeta/lambda so that they had a significantly (P = 0.001) lower level of membrane 70 & 75 kDa fraction and a higher (P = 0.001) level of cytosolic 40 & 43 kDa fraction than rats fed the casein diet. Because protein levels analyzed with a PKC zeta-specific antibody were similar, these differences in PKC zeta/lambda were probably due to changes in PKC lambda expression. PKC beta2 levels did not differ between the dietary groups. Diet had no significant effect on the activity of acid, neutral, or alkaline sphingomyelinase. This study demonstrated that consumption of a high-beef diet is capable of modulating PKC isozyme levels in rat colon, which might be one of the mechanisms whereby red meat affects colon carcinogenesis.

Journal Article↗
PubMed2000

Similar responses in hemostatic factors after consumption of wholemeal rye bread and low-fiber wheat bread.

OBJECTIVE: Both epidemiological and experimental evidence suggests a protective effect of dietary fiber against disease, such as cancer and cardiovascular disease. The effects of fiber on lipoproteins are modest, indicating that other mechanisms may be involved. As the hemostatic effects of different types of fiber are poorly known, we compared the effects of wholemeal rye bread and low-fiber wheat bread on factors related to coagulation, fibrinolysis and platelet function. DESIGN: Subjects consumed rye and wheat bread as part of their habitual diet in a cross-over manner for 4 weeks, with a 4 week washout period between the diet periods. SUBJECTS: Forty healthy subjects (18 men, 22 women), aged 43+/-2 y. RESULTS: Mean daily intake of fiber during the rye bread period was 31 g for men and 26 g for women, while the respective figures for the wheat bread period were 15 g and 12 g. However, no significant differences between the two periods were seen in factor VII coagulant activity (FVIIc), fibrinogen, prothrombin fragments 1+2 (F1+2), tissue plasminogen activator (tPA) plasminogen activator inhibitor 1 (PAI-1) or 2,3,-dinor-thromboxane B2. Fibrin degradation products, D-dimers, were slightly lower after the wheat period (P=0.046). CONCLUSIONS: The results indicate that wheat and rye bread do not differ in their effects on coagulation, fibrinolysis or platelet function. SPONSORSHIP: Fazer Bakeries Ltd, Lahti Finland; Vaasan & Vaasan Ltd, Helsinki, Finland.

Adult↗
PubMed2000

Beef induces and rye bran prevents the formation of intestinal polyps in Apc(Min) mice: relation to beta-catenin and PKC isozymes.

Epidemiological studies suggest that high consumption of red meat and saturated fat and low consumption of fiber are associated with an increased risk of colon cancer. Therefore, we studied whether diets high in red meat or high in different grain fibers as well as inulin, polydisperse beta(2-->1) fructan, could affect the formation of intestinal polyps in Apc(Min) mice. Min mice were fed the following high-fat (40% of energy) diets for 5-6 weeks; a high-beef diet and a casein-based diet without added fiber or casein-based diet with 10% (w/w) oat, rye or wheat bran, or 2.5% (w/w) inulin. One group had a normal low-fat AIN93-G diet. The mice fed the rye-bran diet had the lowest number of polyps in the distal small intestine [15.4 +/- 8.7 (mean +/- SD)], and in the entire intestine (26.4 +/- 12.1). The rye-bran group differed significantly (P = 0. 001-0.004) from the beef group (36.6 +/- 9.4 and 52.8 +/- 13.2). In addition, the beef group differed significantly from the AIN93-G group (P = 0.009) and also from the wheat-bran group (21.0 +/- 6.1 and 35.0 +/- 8.2; P = 0.02) in the distal small intestine. The inulin group (32.9 +/- 14.3 and 49.3 +/- 16.3), on the other hand, was close to the beef group and it differed significantly from the rye-bran group in the distal small intestine. The number of animals bearing tumors in the colon + caecum was only 33% in the rye-bran group when compared with 89% in the beef and 100% in the inulin groups. The mice fed the rye-bran and beef diets had the lowest levels of cytosolic beta-catenin (0.60 +/- 0.42 and 0.67 +/- 0.26) and they differed significantly (P = 0.040 and 0.062) from the mice fed the oat-bran diet (1.46 +/- 0.43). No differences between groups in expression of protein kinase C (PKC) alpha, betaII, delta and zeta were found. The four PKC isozymes were positively correlated with cytosolic beta-catenin levels (r = 0.62-0.68; P < 0.0001).

Animals↗
PubMed2000

Diets enriched with cereal brans or inulin modulate protein kinase C activity and isozyme expression in rat colonic mucosa.

The role of dietary fibres in colon carcinogenesis is controversial. To elucidate the mechanisms by which different dietary fibre sources may affect colonic tumour development, we studied the effects of diets enriched with cereal brans or inulin on protein kinase C (PKC) activity and isozyme expression in rat colon. Male Wistar rats (twelve per group) were fed one of the following AIN-93G-based diets (Reeves et al. 1993) for 4 weeks: a non-fibre high-fat diet or one of the four high-fat diets supplemented with either rye, oat or wheat bran or inulin at 100 g/kg diet. The fat concentration (20 g/100 g) and fatty acid composition of the non-fibre high-fat diet was designed to approximate that in a typical Western-type diet. In the proximal colon, rats fed the inulin diet had a significantly higher membrane PKC activity and a higher membrane PKC delta level than rats fed the non-fibre diet In the distal colon, rats fed the inulin and oat bran diets had a higher total PKC activity and a higher membrane PKC beta 2 level than rats fed the wheat-bran diet. Rats in the non-fibre and wheat-bran groups had the lowest concentrations of luminal diacylglycerol. In conclusion, feeding of wheat bran resulted in low distal PKC activity and expression of PKC beta 2, a PKC isozyme related to colonic cell proliferation and increased susceptibility for colon carcinogenesis, which may explain in part the protective effect of wheat bran against tumour development in a number of experimental colon cancer studies. The increase in PKC activity and PKC beta 2 expression by feeding inulin may be a drawback of inulin as a functional food.

Animals↗
PubMed1999

Green tea extract decreases plasma malondialdehyde concentration but does not affect other indicators of oxidative stress, nitric oxide production, or hemostatic factors during a high-linoleic acid diet in healthy females.

BACKGROUND: Green tea contains polyphenolic catechins which can act as antioxidants and thus decrease the risk for cardiovascular diseases. AIM OF THE STUDY: To investigate whether green tea extract differs from placebo in its effects on markers of antioxidant status, lipid peroxidation, nitric oxide production, thromboxane production, and blood coagulation during a controlled high linoleic acid diet in healthy subjects. METHODS: Twenty healthy non-smoking females (23-50 years) participated in a 4-week controlled intervention study. The experimental diet was rich in linoleic acid (9 en%) and contained fat, protein, and carbohydrates: 27, 14, and 59 en%, respectively. In addition, the subjects ingested encapsulated green tea extract (3 g/d) or placebo mixture in a double-blind manner. Fasting blood samples and five 24-hour urines were collected before and at the end of the 4-week experimental period. Same samples were received from 10 control subjects. RESULTS: Green tea extract significantly decreased plasma malondialdehyde (MDA) concentration in comparison with the placebo treatment. The treatments did not differ in serum lipids, indicators of antioxidant status, urinary 8-isoprostaglandin F2 alpha, 2,3-dinorthromboxane B2, nitric oxide metabolites or coagulation indicators. CONCLUSIONS: We conclude that an amount of green tea extract which corresponds to 10 cups of tea per day for 4 weeks does not have specific effects on several indicators related to risk of cardiovascular diseases in comparison with placebo treatment. The relatively small but significant decrease in lipid peroxidation indicated by decreased plasma MDA was not associated with changes in markers of oxidative stress (urinary 8-isoprostaglandin F2 alpha and blood oxidized glutathione) or hemostasis.

Adult↗
PubMed1999

Phospholipid fatty acid composition and protein kinase C activity in the large intestine of rats fed on butter and coconut-oil diets.

Protein kinase C (PKC) has been proposed to play an important role in the aetiology of colon cancer. Therefore, we investigated whether the amount and type of saturated fat could affect colonic PKC activity by modifying either mucosal phospholipid fatty acid composition or faecal diacylglycerol production. Male Wistar rats (n 13 per group) were fed on diets containing butter or coconut oil at energy levels of 10% and 43% for 4 weeks. The control group received a low-fat diet providing 10% of energy from sunflowerseed oil. PKC activity was higher in the distal than the proximal colon but the quantity or type of fat did not alter PKC activity in either region of the colon. Saturated fats caused moderate changes in the fatty acid composition of caecal phospholipids, which were more obvious in the phosphatidylethanolamine than in the phosphatidylcholine fraction. A significant correlation was found between fatty acid composition of phosphatidylcholine and membrane PKC activity. In particular, there was a positive correlation between the proportion of saturated 14:0 and 18:0 and increased PKC activity while unsaturated 18:2n-6, 20:4n-6 and 16:1n-7 were inversely correlated with PKC activity. No relationship was found between phosphatidylethanolamine fatty acids and PKC activity. Concentration of faecal diacylglycerol was not affected by the diet. Overall the data suggest that diets high in saturated fat may not alter colonic PKC activity to a significant extent.

Analysis of Variance↗