Biomedical subjects

F Thies

Publications and source records attributed to F Thies.

16 recordsLinked to original sources

PubMed2003

The effect of eicosapentaenoic acid on rat lymphocyte proliferation depends upon its position in dietary triacylglycerols.

Animal and human studies have shown that greatly increasing the amount of fish oil [rich in long-chain (n-3) PUFA] in the diet can decrease lymphocyte functions. The effects of a more modest provision of long-chain (n-3) PUFA and whether eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6) have the same effects as one another are unclear. Whether the position of 20:5 or 22:6 in dietary triacylglycerols (TAG) influences their incorporation into immune cells and their subsequent functional effects is not known. In this study, male weanling rats were fed for 6 wk one of 9 diets that contained 178 g lipid/kg and that differed in the type of (n-3) PUFA and in the position of these in dietary TAG. The control diet contained 4.4 g alpha-linolenic acid (18:3)/100 g total fatty acids. In the other diets, 20:5 or 22:6 replaced a portion (50 or 100%) of 18:3, and were in the sn-2 or the sn-1(3) position of dietary TAG. There were significant dose-dependent increases in the proportion of 20:5 or 22:6 in spleen mononuclear cell phospholipids when 20:5 or 22:6 was fed. These increases were at the expense of arachidonic acid and were largely independent of the position of 20:5 or 22:6 in dietary TAG. Spleen lymphocyte proliferation increased dose dependently when 20:5 was fed in the sn-1(3) position of dietary TAG. There were no significant differences in interleukin-2, interferon-gamma or interleukin-10 production among spleen cells from rats fed the different diets. Prostaglandin E(2) production by spleen mononuclear cells was decreased by inclusion of either 20:5 or 22:6 in the diet in the sn-1(3) position. Thus, incorporation of 20:5 or 22:6 into spleen mononuclear cell phospholipids is not influenced by the position in dietary TAG. However, the pattern of incorporation may be influenced, and there are some differential functional effects of the position of long-chain (n-3) PUFA in dietary TAG. A moderate increase in the intake of 20:5 at the sn-1(3) position of dietary TAG increases lymphocyte proliferation.

Animals↗

PubMed2002

Fatty acids and lymphocyte functions.

The immune system acts to protect the host against pathogenic invaders. However, components of the immune system can become dysregulated such that their activities are directed against host tissues, so causing damage. Lymphocytes are involved in both the beneficial and detrimental effects of the immune system. Both the level of fat and the types of fatty acid present in the diet can affect lymphocyte functions. The fatty acid composition of lymphocytes, and other immune cells, is altered according to the fatty acid composition of the diet and this alters the capacity of those cells to produce eicosanoids, such as prostaglandin E2, which are involved in immunoregulation. A high fat diet can impair lymphocyte function. Cell culture and animal feeding studies indicate that oleic, linoleic, conjugated linoleic, gamma-linolenic, dihomo-gamma-linolenic, arachidonic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acids can all influence lymphocyte proliferation, the production of cytokines by lymphocytes, and natural killer cell activity. High intakes of some of these fatty acids are necessary to induce these effects. Among these fatty acids the long chain n-3 fatty acids, especially eicosapentaenoic acid, appear to be the most potent when included in the human diet. Although not all studies agree, it appears that fish oil, which contains eicosapentaenoic acid, down regulates the T-helper 1-type response which is associated with chronic inflammatory disease. There is evidence for beneficial effects of fish oil in such diseases; this evidence is strongest for rheumatoid arthritis. Since n-3 fatty acids also antagonise the production of inflammatory eicosanoid mediators from arachidonic acid, there is potential for benefit in asthma and related diseases. Recent evidence indicates that fish oil may be of benefit in some asthmatics but not others.

Adult↗

PubMed2001

Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults.

Greatly increasing the amounts of flaxseed oil [rich in alpha-linolenic acid (ALNA)] or fish oil (FO); [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease inflammatory cell functions and so might impair host defense. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA, or FO on inflammatory cell numbers and functions and on circulating levels of soluble adhesion molecules. Healthy subjects aged 55 to 75 yr consumed nine capsules per day for 12 wk. The capsules contained placebo oil (an 80:20 mix of palm and sunflowerseed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA, or DHA or FO. Subjects in these groups consumed 2 g ALNA; approximately 700 mg GLA, ARA, or DHA; or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily from the capsules. Total fat intake from the capsules was 4 g per day. None of the treatments affected inflammatory cell numbers in the bloodstream; neutrophil and monocyte phagocytosis or respiratory burst in response to E. coli; production of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in response to bacterial lipopolysaccharide; or plasma concentrations of soluble intercellular adhesion molecule-1. In contrast, the ALNA and FO treatments decreased the plasma concentrations of soluble vascular cell adhesion molecule-1 (16 and 28% decrease, respectively) and soluble E-selectin (23 and 17% decrease, respectively). It is concluded that, in contrast to previous reports using higher amounts of these fatty acids, a moderate increase in consumption of long-chain n-6 or n-3 polyunsaturated fatty acids does not significantly affect inflammatory cell numbers or neutrophil and monocyte responses in humans and so would not be expected to cause immune impairment. Furthermore, we conclude that moderate levels of ALNA and FO, which could be incorporated into the diet, can decrease some markers of endothelial activation and that this mechanism of action may contribute to the reported health benefits of n-3 fatty acids.

Aged↗

PubMed2001

Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y.

BACKGROUND: Animal studies showed that dietary flaxseed oil [rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid (ALA)], evening primrose oil [rich in the n-6 polyunsaturated fatty acid gamma-linolenic acid (GLA)], and fish oil [rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] can decrease natural killer (NK) cell activity. There have been no studies of the effect on NK cell activity of adding these oils to the diet of humans. OBJECTIVE: Our objective was to determine the effect of dietary supplementation with oil blends rich in ALA, GLA, arachidonic acid (AA), DHA, or EPA plus DHA (fish oil) on the NK cell activity of human peripheral blood mononuclear cells. DESIGN: A randomized, placebo-controlled, double-blind, parallel study was conducted. Healthy subjects aged 55-75 y consumed 9 capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil and oils rich in ALA, GLA, AA, DHA, or EPA plus DHA. Subjects in these groups consumed 2 g ALA, 770 mg GLA, 680 mg AA, 720 mg DHA, or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily, respectively. Total fat intake from the capsules was 4 g/d. RESULTS: The fatty acid composition of plasma phospholipids changed significantly in the GLA, AA, DHA, and fish oil groups. NK cell activity was not significantly affected by the placebo, ALA, GLA, AA, or DHA treatment. Fish oil caused a significant reduction (mean decline: 48%) in NK cell activity that was fully reversed by 4 wk after supplementation had ceased. CONCLUSION: A moderate amount of EPA but not of other n-6 or n-3 polyunsaturated fatty acids can decrease NK cell activity in healthy subjects.

Aged↗

PubMed2001

Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans.

Animal and human studies have shown that greatly increasing the amounts of flax seed oil [rich in the (n-3) polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALNA)] or fish oil [FO; rich in the long chain (n-3) PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease mitogen-stimulated lymphocyte proliferation. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA or FO on the proliferation of mitogen-stimulated human peripheral blood mononuclear cells (PBMC) and on the production of cytokines by those cells. The study was randomized, placebo-controlled, double-blinded and parallel. Healthy subjects ages 55-75 y consumed nine capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA or DHA or FO. Subjects in these groups consumed 2 g of ALNA or 770 mg of GLA or 680 mg of ARA or 720 mg of DHA or 1 g of EPA plus DHA (720 mg of EPA + 280 mg of DHA) daily from the capsules. Total fat intake from the capsules was 4 g/d. The fatty acid composition of PBMC phospholipids was significantly changed in the GLA, ARA, DHA and FO groups. Lymphocyte proliferation was not significantly affected by the placebo, ALNA, ARA or DHA treatments. GLA and FO caused a significant decrease (up to 65%) in lymphocyte proliferation. This decrease was partly reversed by 4 wk after stopping the supplementation. None of the treatments affected the production of interleukin-2 or interferon-gamma by PBMC and none of the treatments affected the number or proportion of T or B lymphocytes, helper or cytotoxic T lymphocytes or memory helper T lymphocytes in the circulation. We conclude that a moderate level GLA or EPA but not of other (n-6) or (n-3) PUFA can decrease lymphocyte proliferation but not production of interleukin-2 or interferon-gamma.

Aged↗

PubMed2001

Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations.

Soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin (termed sICAM-1, sVCAM-1 and sE-selectin respectively) are found in the plasma, and are elevated during inflammatory conditions in which there is increased expression of the cellular forms of the molecules on endothelial and other cells. sICAM-1, sVCAM-1 and sE-selectin concentrations were measured in the plasma of 140 healthy Caucasian subjects aged between 18 and 75 years (100 males/40 females). sICAM-1 concentrations varied between 59.9 and 299.7 ng/ml (median 150 ng/ml), sVCAM-1 concentrations varied between 222.8 and 1672.9 ng/ml (median 662 ng/ml) and sE-selectin concentrations varied between 12.4 and 90.3 ng/ml (median 45.5 ng/ml). There were significant positive linear correlations between age and the plasma concentrations of sICAM-1 (r=0.580; P<0.001) and sVCAM-1 (r=0.392; P<0.001), which were retained when the effects of gender, body mass index and fasting plasma triacylglycerol and total cholesterol concentrations were controlled for. The significant positive linear correlation between age and the plasma concentration of sE-selectin (r=0.234; P=0.027) was lost when other variables were controlled for. Male subjects <40 years of age had significantly lower plasma concentrations of both sICAM-1 and sVCAM-1 than males >55 years of age (both P<0.001), but the difference in plasma sE-selectin concentrations between the age groups did not reach significance (P=0.073). Subgroups of 16 males aged <40 years and 12 elderly subjects (>55 years of age) participated in a doubled-blind, placebo-controlled study of fish oil supplementation over 12 weeks. The level of eicosapentaenoic acid in plasma phospholipids did not change with placebo supplementation, but was significantly increased with fish oil supplementation in both young male and elderly subjects (median increase 200%). sICAM-1, sVCAM-1 and sE-selectin concentrations were unaffected by supplementation with placebo in either young male or elderly subjects. sICAM-1 concentrations were unaffected by fish oil supplementation. sE-selectin concentrations were significantly increased by fish oil supplementation in young males (P=0.043; median increase 38%), but fish oil tended to decrease plasma sE-selectin concentrations in the elderly subjects (P=0.075), with a median decrease of 11%. sVCAM-1 concentrations were unaffected by fish oil supplementation in young males. Fish oil supplementation significantly decreased plasma sVCAM-1 concentrations in the elderly subjects (P=0.043), with a median decrease of 20% (range 16-60%). These observations suggest that fish oil decreases endothelial activation in elderly subjects.

Adult↗

PubMed2000

Extracellular release of free fatty acids by rat T lymphocytes is stimulus-dependent and is affected by dietary lipid manipulation.

[(3)H]-Arachidonic acid-labelled rat T lymphocytes released radioactivity extracellularly when stimulated by the calcium ionophore A23187 or by monoclonal antibodies to some cell surface structures (CD2, CD5, CD11a, CD18, CD54, T-cell receptor) but not to others (CD49d, CD62L); release was greater with the calcium ionophore. Almost all of the radioactivity released from anti-CD2-stimulated lymphocytes was recovered in the free fatty acid fraction, whereas only about 50 per cent of that released after A23187 stimulation was recovered in this fraction. A23187 stimulation resulted in release of arachidonic acid from a variety of phospholipids (phosphatidylinositol, phosphatidylcholine and perhaps phosphatidylethanolamine), while the monoclonal antibody stimulation released arachidonic acid from phosphatidylinositol and perhaps phosphatidylcholine. Unstimulated lymphocytes released a range of fatty acids extracellularly, with palmitic acid accounting for 35-40 per cent and arachidonic acid for 5 per cent of released fatty acid. Stimulation of lymphocytes with either anti-CD2 or A23187 increased total fatty acid release 1.5- to 1.8-fold. In both cases palmitic acid remained the most predominant fatty acid released but the contribution of arachidonic acid increased. The type of lipid fed to the rats significantly influenced the amount and type of fatty acid released. Fish oil feeding significantly reduced extracellular fatty acid release by stimulated lymphocytes.

Animals↗

PubMed2000

Effect of whole linseed (Linum usitatissimum) in the diet of finishing pigs on growth performance and on the quality and fatty acid composition of various tissues.

Pigs (n 144, 30 kg liveweight) were allocated to one of three diets differing in the level of whole linseed (Linum usitatissimum, also known as flaxseed). The diets contained 0, 50 and 100 g/kg for diets L0, L50 and L100 respectively, while containing a constant oil content (60 g/kg). Pigs were slaughtered at a liveweight of 77-87 kg. With the exception of a slight difference in feed intake, there was no effect of diet on production characteristics or carcass traits. Levels of alpha-linolenic acid were increased in all tissues studied as the amount of linseed in the diet increased. In the plasma, m. longissimus thoracis, liver and kidney eicosapentaenoic acid concentration increased markedly. Docosapentaenoic acid concentration increased in the muscle, liver and kidney, whereas in the plasma higher levels of docosahexaenoic acid were observed. None of the longer-chain fatty acids (C20 or longer) were detected in the subcutaneous fat. The changes in fatty acid composition resulted in marked changes to the n-6: n-3 and arachidonic: eicosapentaenoic acid ratios. Feeding whole linseed had no negative effect on the oxidative stability of the meat. Sensory panel results showed no significant differences by diet except for a reduction in abnormal odour (odour perceived by panellists to be abnormal in pigmeat) in the L50 diet and a reduction in the skatole odour (odour of 3-methylindole) in the pigs fed on diet L100. It is concluded that increasing the linseed content of pig diets up to 100 g/kg has no adverse effect on the carcass or meat quality whilst enhancing the levels of n-3 fatty acids which have a potentially positive health effect in man.

Animal Feed↗

PubMed1999

Dose-dependent effects of dietary gamma-linolenic acid on rat spleen lymphocyte functions.

Feeding rodents a diet rich in evening primrose oil (EPO), which contains 5-10 g gamma-linolenic acid (GLA)/100 g total fatty acids, has been shown to decrease lymphocyte proliferation and natural killer cell activity. However, EPO contains a very high level of linoleic acid which itself can affect lymphocyte functions and it is not clear to what extent the effects of EPO can be attributed to GLA. The current study investigated the effect of two levels of GLA in the rat diet upon immune cell functions; the level of linoleic acid was maintained below 30 g/100 g total fatty acids. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g or 10 g GLA/100 g total fatty acids in place of a proportion of linoleic acid. The total polyunsaturated fatty acid content and the n-6 to n-3 polyunsaturated fatty acid ratio of the diet were maintained at 35 g/100 g total fatty acids and 7, respectively. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet, with an increase in the proportions of GLA and dihomo-gamma-linolenic acid when the diets containing GLA were fed; these diets also increased the proportion of arachidonic acid in spleen leukocytes. Spleen lymphocyte proliferation in response to concanavalin A was significantly reduced (by 60%) by feeding the diet containing the higher level of GLA, but not by the diet containing the lower level of GLA. Spleen natural killer cell activity and prostaglandin E (PGE) production by spleen leukocytes were not significantly affected by inclusion of GLA in the diet, although there was a tendency towards decreased natural killer cell activity by cells from rats fed the high GLA diet. Thus, this study shows that dietary GLA is capable of altering the fatty acid composition of cells of the immune system and of exerting some immunomodulatory effects, but that the level of GLA in the diet must exceed 4.4 g/100 g total fatty acids for these effects to become apparent.

Animals↗

PubMed1999

Manipulation of the type of fat consumed by growing pigs affects plasma and mononuclear cell fatty acid compositions and lymphocyte and phagocyte functions.

To investigate the immunological effect of feeding pigs different dietary lipids, 3-wk-old, weaned pigs were fed for 40 d on one of five diets, which differed only in the type of oil present (the oil contributed 5% by weight of the diet and the total fat content of the diets was 8% by weight). The oils used were soybean (control diet), high-oleic sunflower oil (HOSO), sunflower oil (SO), canola oil (CO), and fish oil (FO; rich in long-chain [n-3] polyunsaturared fatty acids). There were no significant differences in initial or final animal weights, weight gains, or health scores among the groups. There were no significant differences in the concentration of anti-Escherichia coli vaccine antibodies in the gut lumens of pigs fed the different diets. The fatty acid composition of the diet markedly affected the fatty acid composition of the plasma and of mononuclear cells (a mixture of lymphocytes, monocytes, and macrophages) prepared from the blood, lymph nodes, or thymus. The FO feeding resulted in a significant increase in the number of circulating granulocytes. The FO feeding significantly decreased the proportion of phagocytes engaged in uptake of E. coli and decreased the activity of those phagocytes that were active. The proliferation of lymphocytes in cultures of whole blood from pigs fed the HOSO, SO, or FO diets was less than in those from pigs fed the CO diet. Proliferation of lymph node lymphocytes from SO- or FO-fed pigs was less than that from control, CO-, or HOSO-fed pigs. The natural killer cell activity of blood lymphocytes from pigs fed the FO diet was significantly reduced compared with those from pigs fed the CO diet. The concentration of PGE2 in the medium of cultured blood, lymph node, or thymic mononuclear cells was lower if the cells came from pigs fed the FO diet. Thus, the type of oil included in the diet of growing pigs affects the numbers and functional activities of immune cells in different body compartments.

Animal Feed↗

PubMed1998

Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity.

Weanling rats were fed on high-fat (178 g/kg) diets which contained 4.4 g alpha-linolenic (ALA), gamma-linolenic, arachidonic (ARA), eicosapentaenoic (EPA), or docosahexaenoic acid (DHA)/100 g total fatty acids. The proportions of all other fatty acids, apart from linoleic acid, and the proportion of total polyunsaturated fatty acids (PUFA) (approximately 35 g/100 g total fatty acids) were constant, and the n-6 to n-3 PUFA ratio was maintained as close to 7 as possible. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Prostaglandin E2 production was enhanced from leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA- or DHA-fed rats. Replacing dietary ALA with EPA resulted in diminished ex vivo lymphocyte proliferation and natural killer (NK) cell activity and a reduced cell-mediated immune response in vivo. In contrast, replacing ALA with DHA reduced ex vivo lymphocyte proliferation but did not affect ex vivo NK cell activity or the cell-mediated immune response in vivo. Replacement of a proportion of linoleic acid with either gamma-linolenic acid or ARA did not affect lymphocyte proliferation, NK cell activity, or the cell-mediated immune response. Thus, this study shows that different n-3 PUFA exert different immunomodulatory actions, that EPA exerts more widespread and/or stronger immunomodulatory effects than DHA, that a low level of EPA is sufficient to influence the immune response, and that the immunomodulatory effects of fish oil may be mainly due to EPA.

Animals↗

PubMed1998

Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of fish oil upon rat lymphocytes.

Fish oil is rich in the long chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); typically these fatty acids constitute 20 to 25 g/100 g total fatty acids in fish oil. Feeding rodents diets rich in fish oil has been shown to decrease lymphocyte proliferation and natural killer cell activity. It is not known what level of EPA + DHA is required in the diet to exert these effects. This question was addressed in the current study. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g alpha-linolenic acid (control) or 4.4 g EPA + DHA (4.4 EPA + DHA) or 6.6 g EPA + DHA (6.6 EPA + DHA)/100 g total fatty acids. The n-6 to n-3 polyunsaturated fatty acid ratio was maintained at approximately 7. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Spleen lymphocyte proliferation in response to concanavalin A, spleen natural killer cell activity and PGE2 production by spleen leukocytes were reduced by feeding the EPA + DHA diets compared with feeding the control diet; the 4.4 and 6.6 EPA + DHA diets caused very similar reductions. The 4.4 EPA + DHA diet reduced popliteal lymph node weight following a localised graft versus host response; this response was not investigated in rats fed the 6.6 EPA + DHA diet. The reductions in lymphocyte functions and in the in vivo graft versus host response caused by the EPA + DHA diets were similar to those previously reported following the feeding of diets rich in fish oil. Thus, this study shows that diets containing relatively low levels of EPA + DHA (20 to 25% of the level found in fish oil) exert immunomodulatory effects. Furthermore, this study suggests that the maximal effect of EPA + DHA is exerted when these fatty acids constitute a level of less than or equal to 4.4 g/100 g total dietary fatty acids.

Animals↗

PubMed1998

Dietary fish oil suppresses human colon tumour growth in athymic mice.

1. Human colon tumour growth, initiated by subcutaneous inoculation of HT29 cells, was measured in athymic mice fed ad libitum on high-fat (210 g/kg) diets rich in coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO); a low fat (LF; 25 g/kg) diet was used as the control. In one experiment the mice were fed the experimental diets for 3 weeks before HT29 cell inoculation and were killed 2 weeks post-inoculation. In a second experiment the mice were maintained on the LF diet until 4 days post-HT29 cell inoculation; they were then fed the experimental diets for 17 days. 2. Compared with mice fed the LF diet, tumour size was increased in mice fed the CO, OO or SO diets for 3 weeks before HT29 cell inoculation; FO feeding did not significantly increase tumour size. 3. Feeding mice the CO or OO diets from 4 days post-inoculation increased tumour growth rate and tumour size compared with feeding the LF, SO or FO diets; tumour growth rate and size did not differ among mice fed the latter diets. 4. The fatty acid composition of the tumours was markedly influenced by the fatty acid composition of the diet. 5. We conclude that human colon tumour growth is influenced by the type of fat consumed in the diet. Human colon tumour growth in this model is promoted by feeding high fat diets rich in medium chain saturated fatty acids (CO) or monounsaturated fatty acids (OO). A high fat diet, rich in long chain n - 3 polyunsaturated fatty acids (FO), does not promote colon tumour growth. The effect of a high fat diet rich in n - 6 polyunsaturated fatty acids (SO) depends upon the time at which it is fed: if fed before tumour cell inoculation such a diet promotes tumour growth, whereas if fed once tumour growth is initiated it does not. This suggests that n - 6 polyunsaturated fatty acids promote the initiation of colon tumour growth, but do not exert growth-promoting effects on colon tumours once they are established.

Adipose Tissue↗

PubMed1996

Xenobiotic biotransformation in unicellular green algae. Involvement of cytochrome P450 in the activation and selectivity of the pyridazinone pro-herbicide metflurazon.

The N-demethylation of the pyridazinone pro-herbicide metflurazon into norflurazon implies a toxification in photosynthetic organisms. This is confirmed by quantitative structure activity relationships determined for two unicellular green algae, Chlorella sorokiniana and Chlorella fusca; however, the latter is 25 to 80 times more sensitive to metflurazon. This sensitivity is linked to differences in the N-demethylase activity of both algae, as determined by an optimized in vivo biotransformation assay. Apparent K(m) values of the metflurazon-N-demethylase indicate a 10-fold higher affinity for this xenobiotic substrate for Chlorella fusca. Furthermore, algal metflurazon-N-demethylation is characterized by distinct variations in activity, depending on the stage of cell development within the cell cycle. Several well-established inhibitors of cytochrome P450-mediated reactions, including piperonylbutoxide, 1-aminobenzotriazole, 1-phenoxy-3-(1H-1,2,4-triol-1yl)-4-hydroxy-5,5-dimethylhexane++ +, and tetcyclacis, as well as cinnamic acid, a potential endogenous substrate, inhibited the N-demethylation of metflurazon. The results suggest that the N-demethylation of metflurazon by both algae is mediated by a cytochrome P450 monooxygenase. The determination of antigenic cross-reactivity of algal proteins with heterologous polyclonal antibodies originally raised against plant P450s, anti-cinnamic acid 4-hydroxylase (CYP73A1), anti-ethoxycoumarin-O-dealkylase, anti-tulip allene oxidase (CYP74), and an avocado P450 (CYP71A1) or those of bacterial origin, CYP105A1 and CYP105B1, suggests the presence of distinct P450 isoforms in both algae.

Biotransformation↗

PubMed1994

Preferential incorporation of sn-2 lysoPC DHA over unesterified DHA in the young rat brain.

The uptake and metabolism of [3H]docosahexaenoic acid (DHA) esterified at the sn-2 position of lysophosphatidylcholine (lysoPC DHA) and in the unesterified form, both bound to albumin, was studied in 20-day-old rats. LysoPC DHA was preferentially recovered in the brain (4-5% of the injected radioactivity) over the unesterified form of DHA (0.3-0.4%). Conversely, the lysoPC form was taken up less than or at the same extent as the unesterified form by the liver, heart, and kidney. In the brain, DHA was mainly recovered in phosphatidylethanolamine whether the esterified or the unesterified form was used, although DHA from lysoPC was esterified at the same extent in phosphatidylcholine and phosphatidylethanolamine after 2.5 min. The uptake of labeled palmitic, oleic, linoleic, and arachidonic acids, esterified or not in lysophosphatidylcholine, was also studied in brain, liver, heart, and kidney. Only the brain preferentially incorporated unsaturated (but not saturated) lysoPC, with the uptake increasing with the degree of unsaturation of the fatty acid moiety. These results strongly suggest that the young rat brain specifically utilizes albumin-lysoPC-containing polyunsaturated fatty acids.

Animals↗

PubMed1990

[Cisplatin-Vepeside versus Endoxan-Vepeside in the treatment of small cell bronchial cancer. A randomized study].

Within the framework of a multi-centre prospective randomised therapeutic trial, 150 patients with small-cell lung cancer (SCLC) were treated with cisplatin/vepesid and endoxan/vepesid. The aim of the study was to establish whether cisplatin--which although effective is commonly associated with adverse effects--can be replaced by endoxan. The sequence of treatment was oriented to the stage and course of the tumour disease. In the event of a treatment failure, cross-over to the alternative combination was effected. In terms of remission rates, the combination cisplatin/vepesid proved to be more effective than endoxan/vepesid, in particular in the case of patients with extensive disease. With respect to duration of remission and survival duration, however, no significant differences were to be seen.

Adult↗