Biomedical subjects

M J James

Publications and source records attributed to M J James.

At least 55 records · Page 3Linked to original sources

PubMed1994

Ratios of linoleic acid to alpha-linolenic acid in formulas for term infants.

Commercial infant formulas with a ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) of 10:1 or higher are nutritionally inadequate; the tissue levels of docosahexaenoic acid (DHA) are lower and the visual function indices are reduced in infants who are fed these formulas. All the evidence points to using LA:ALA ratios of less than 8:1, but there has been only one study in infants that used formulas with reduced LA:ALA ratios, and only biochemical indices were monitored. There is a need for both short-term studies to establish the ratios of LA to ALA that will make possible the accumulation of DHA to levels close to those in breast-fed infants and long-term trials to determine the effects of such fat blends on growth and development.

Breast Feeding↗

PubMed1994

Dietary substitution with an alpha-linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentrations in tissues.

Thirty healthy male volunteers were randomly allocated into two dietary treatment groups. The flaxseed group (n = 15) maintained a diet high in alpha-linolenic acid (alpha-LA; 18:3n-3) and low in linoleic acid (LA; 18:2n-6) by using a flaxseed oil and spread that are high in alpha-LA. The control group (n = 15) maintained a diet high in LA and low in alpha-LA, typifying a Western diet. Both groups maintained their diets for 4 wk, followed by another 4-wk period in which they supplemented the diets with fish oil [1.62 g eicosapentaenoic acid (EPA, 20:5n-3) daily and 1.08 g docosahexaenoic acid (DHA, 22:6n-3) daily] in a triglyceride form. The flaxseed oil-containing diet resulted in significant increases in alpha-LA concentrations in the plasma phospholipid, cholesteryl ester, and triglyceride fractions (eightfold increase) and neutrophil phospholipids (50% increase). EPA concentrations increased by 2.5-fold in the plasma lipid fractions and neutrophil phospholipids. After fish-oil supplementation EPA concentrations increased in parallel in both dietary groups, remaining higher in the flaxseed group for both the plasma lipid fractions and neutrophil phospholipids. The results indicate that alpha-LA-rich vegetable oils can be used in a domestic setting (in conjunction with a background diet low in LA) to elevate EPA in tissues to concentrations comparable with those associated with fish-oil supplementation.

Adult↗

PubMed1994

Effect of exercise on 99mTc-DTPA clearance from knees with effusions.

OBJECTIVE: To devise and use a method for assessing the effect of dynamic exercise on synovial blood flow in knees with effusions. METHODS: The clearance rate of intraarticular 99mTc-DTPA (diethylene triamine pentaacetic acid) was continuously monitored by a gamma camera during periods of rest or flexion. The rate of 99mTc-DTPA disappearance during a fixed period of exercise which was interposed between 2 rest periods was estimated by extrapolation between the clearance curves for the 2 rest periods. RESULTS: Cycling and walking increased the clearance rate, straight leg raising had no effect, and flexion decreased the clearance rate. CONCLUSION: Our results suggest that some dynamic exercises can increase the rate of synovial blood flow in joints with effusions. This outcome may be beneficial in inflamed joints which are chronically hypoxic due to elevated intraarticular pressure and consequent chronic synovial ischemia.

Arthritis↗

PubMed1994

The effect of methotrexate on ex vivo lipoxygenase metabolism in neutrophils from patients with rheumatoid arthritis.

OBJECTIVE: To examine the effect of methotrexate (MTX) administered in vivo on the production of the 5-lipoxygenase (5-LO) metabolites of arachidonic acid by neutrophils from subjects with rheumatoid arthritis. METHODS: Neutrophils were isolated from peripheral blood samples taken 12 h before and 12 h after the ingestion of an oral dose of MTX and stimulated in vitro by calcium ionophore A23187. Lipid extracts of cell suspensions were assayed for leukotriene B4 (LTB4), the all-trans isomers of LTB4, 20-hydroxy LTB4 and 5-hydroxyeicosatetraenoic acid by high pressure liquid chromatography. RESULTS: An increase in the production of all measured 5-LO metabolites was seen between the pre and postdose assessments. CONCLUSION: Our results do not support the putative inhibitory effect of MTX on 5-LO metabolism.

Arthritis, Rheumatoid↗

PubMed1993

Effect of dietary supplementation with n-9 eicosatrienoic acid on leukotriene B4 synthesis in rats: a novel approach to inhibition of eicosanoid synthesis.

Studies were undertaken to assess the biochemical effects of dietary supplementation with n-9 eicosatrienoic acid (ETrA), an arachidonic acid analogue that is normally present in cell membranes at very low levels but is raised in the presence of essential fatty acid deficiency (EFAD). The incorporation of dietary ETrA into rat neutrophils and its effect on A23187-stimulated 5-lipoxygenase metabolism in these cells was examined; in addition, the effect of ETrA was compared with that of another arachidonic acid analogue, eicosapentaenoic acid (EPA), which is known to accumulate in cell membranes and inhibit synthesis of leukotriene B4 (LTB4) a product of the 5-lipoxygenase metabolic pathway. Rats were fed a defined diet that was sufficient in essential fatty acids and that contained EPA or ETrA (0.014% of energy) or no added fatty acid, for 3 wk. In the cells from ETrA-fed rats, LTB4 synthesis was inhibited relative to control values, but synthesis of the other products of 5-lipoxygenase metabolism, 5-hydroxyeicosatetraenoic acid (5-HETE) and the all-trans isomers of LTB4, were not inhibited. This pattern indicates inhibition of LTA hydrolase in ETrA-fed rats. In EPA-fed rats, there was inhibition of LTB4 and the all-trans isomers of LTB4, but there was no inhibition of 5-HETE. This pattern indicates inhibition of LTA synthase in EPA-fed rats. The results establish that dietary ETrA effectively inhibits synthesis of the inflammatory mediator, LTB4, and suggest that ETrA may confer antiinflammatory benefits similar to those observed with EFAD or dietary fish oil (which contains EPA). Because ETrA is substantially less unsaturated than EPA, it can be expected to have greater chemical stability, which could be an important practical advantage when used as a dietary constituent or supplement.

8,11,14-Eicosatrienoic Acid↗

PubMed1993

The effect of methotrexate on lipoxygenase metabolism in neutrophils from rats: in vitro and ex vivo studies.

Studies were undertaken to examine the effect of methotrexate (MTX) administered in vivo or added in vitro upon the production of the 5-lipoxygenase (5-LO) metabolites of arachidonic acid (AA) by rat neutrophils. Peptone-induced peritoneal exudate cells were stimulated by A23187 and the cell suspensions assayed for leukotriene B4 (LTB4), the all-trans isomers of LTB4 and 5-hydroxyeicosatetraenoic acid (5-HETE) using high-pressure liquid chromatography. MTX added in vitro to rat cells was weakly inhibitory; however, no inhibition of LTB4 production was seen following in vivo administration of MTX by oral, subcutaneous or intraperitoneal routes. On the basis of these findings, inhibition of 5-LO metabolism does not appear to explain the anti-inflammatory effects of MTX.

Administration, Oral↗

PubMed1993

Simple relationships exist between dietary linoleate and the n-6 fatty acids of human neutrophils and plasma.

Eicosanoids, the enzymatically oxygenated products of arachidonic acid (AA), appear to be overproduced in some disorders of inflammation. Dietary strategies for decreasing tissue AA require information on the relationships between dietary linoleic acid (LA) and tissue concentrations of AA. The use of either high- or low-LA spreads and cooking oils by healthy male volunteers resulted in a range of LA intakes of 2.5-17.5% of energy, as estimated by diet-diary analysis. Analysis of LA and AA concentrations in neutrophils and plasma lipid fractions from these subjects indicated that there were positive linear relationships between dietary LA and the LA concentrations in neutrophil phospholipids, plasma triglycerides, and plasma cholesteryl esters. By contrast, differences in dietary LA within a broad range were not associated with differences in concentrations of AA in these same neutrophil and plasma fractions. AA concentrations were decreased by supplementation of the diet with 4 g fish oil (1.6 g eicosapentaenoic acid, 0.3 g docosahexaenoic acid). The results suggest that the LA content of tissue lipids may be used to estimate LA intake, and the reduction of dietary LA by using standard dietary strategies is not likely to lead to reduction in tissue AA whereas this can be accomplished by fish-oil supplementation.

Adult↗

PubMed1993

Partial mediation by nitric oxide of the relaxation of human isolated detrusor strips in response to electrical field stimulation.

1. A method for reproducing relaxation of human isolated detrusor smooth muscle in vitro in response to electrical field stimulation is described. 2. The parameters of stimulation associated with relaxation were those which would be expected to give a largely nerve-mediated response: the relaxations were not reduced by tetrodotoxin (3 x 10(-7) M) and were therefore not dependent on voltage sensitive sodium channels. 3. The relaxations were decreased (mean 74.1%) by nitro L-arginine (NOARG, 10(-5) M). 4. Methylene blue (10(-5) M), an inhibitor of soluble guanylate cyclase, abolished the relaxations. 5. These results indicate that there may be a relaxation mechanism in the human bladder which is at least partly mediated via the production of nitric oxide.

Arginine↗

PubMed1992

Incorporation of dietary oleate, linoleate, alpha-linolenate and eicosapentaenoate into the plasma lipid fractions of four strains of rat.

Four strains of rat (Dark Agouti, DA; Ginger Hooded, GH; Portion, P; Hooded Wistar, HW) were fed elemental diets containing different sources of fat at the 10% (w/w) level. The dietary fats used included the following oils; olive (rich in oleate), sunflower (rich in linoleate), linseed (rich in alpha-linolenate) and fish (rich in eicosapentaenoate and docosahexaenoate). Differences between strains in response to individual diets were modest compared with the much greater differences achieved by the dietary treatments. In general, the changes in polyunsaturated fatty acid (PUFA) levels in the plasma lipids of all rat strains followed the major PUFA in the diet. There were, however, strong interactions between dietary n-6 and n-3 PUFA which affected not only the level of particular PUFA in lipid fractions but also the lipid fraction in which a particular PUFA appeared. Our findings indicate that a response to dietary fats in the plasma lipids of one strain of rat can be expected to occur with relatively minor variations in other commonly used rat strains.

Animals↗

PubMed1992

Inhibition of human neutrophil leukotriene B4 synthesis by combination auranofin and eicosapentaenoic acid.

It has been demonstrated that both auranofin and eicosapentaenoic acid (EPA) have anti-inflammatory properties and both inhibit neutrophil leukotriene B4 (LTB4) synthesis. In the present study, we examined interactions between auranofin and EPA with regard to inhibition of human neutrophil LTB4 synthesis. Auranofin inhibited A23187-stimulated LTB4 synthesis, but the dose required for inhibition of LTB4 was greater than that required for inhibition of other 5-lipoxygenase metabolites; namely, the all-trans isomers of LTB4 and 5-hydroxyeicosatetraenoic acid. These results were explained after a comparison of the rates of synthesis of these 5-lipoxygenase metabolites in the presence and absence of added arachidonic acid which led to the conclusion that leukotriene A hydrolase, the enzyme catalysing the formation of LTB4, was saturated with substrate and rate-limiting for LTB4 synthesis during A23187 stimulation. In combination, auranofin and EPA had a simple additive effect on inhibition of the 5-lipoxygenase pathway. Favorable drug/EPA combinations have the potential to provide a beneficial anti-inflammatory effect with lower levels of each component than are required when used individually.

Arachidonic Acid↗

PubMed1992

Biological activity of prostaglandin E3 with regard to oedema formation in mice.

The biological activity of PGE3 with regard to oedema formation in mice was examined. Paw swelling was measured 30 minutes after injection of 10 microliters PGE2 or PGE3 into the plantar region of the hind paw. Doses investigated ranged from 1 ng-10 micrograms. Both PGE2 and PGE3 had substantial oedemogenic activity in this system.

Alprostadil↗

PubMed1992

Effect of n-3 and n-6 dietary fats on the lipoxygenase products from stimulated rat neutrophils.

Fish oil was fed to rats in combination with an equal amount of olive, sunflower or linseed (flax) oil in semisynthetic diets for 3 weeks. Following stimulation of isolated neutrophils with calcium ionophore the levels of leukotrienes (LT) were determined by HPLC. Graphical presentation of the resultant data show a direct linear relationship between LTB production and substrate concentration with no preferential conversion of n-3 or n-6 substrates. In addition the results highlighted the greater conversion of eicosapentaenoic acid (EPA) and arachidonic acid (AA) to 5-hydroxy metabolites in stimulated neutrophils. There is no suggestion in our results of inhibition of any of the enzymatic conversion steps between EPA or AA and LTB production by any of the dietary fatty acids except by altering the EPA/AA ratio in neutrophil membranes.

Animals↗

PubMed1992

Linoleate inhibits EPA incorporation from dietary fish-oil supplements in human subjects.

Thirty healthy male subjects were randomly allocated into one of two treatment groups: group H subjects were maintained on a high-linoleic acid (LA) diet with the saturated fatty acids kept low and those in group L were kept on a low-LA, low saturate diet. After a 3-wk run-in period, subjects consumed a fish-oil supplement containing 1.6 g eicosapentaenoic acid (EPA)/d and 0.32 g docosahexaenoic acid as triglycerides for a further 4 wk. The diets alone resulted in a significant change in neutrophil phospholipid LA (H = 12.7 +/- 2.9%, L = 9.0 +/- 0.9%; P less than 0.05). Dietary supplementation with fish oil resulted in a significant increase in EPA in neutrophil phospholipids that was greater in group L (mean 2.0 +/- 0.4%) than group H (mean 1.5 +/- 0.3%; P less than 0.005). Reductions in arachidonic acid concentrations in neutrophil membranes were not different, nor could differences in leukotriene B4 production be detected. Our study indicates that the ingestion of n-6 fatty acids within the diet is an important determinant of EPA incorporation into neutrophil membranes.

Diet↗

PubMed1992

Determinants of synovial fluid lactate concentration.

The resting intraarticular pressure and the type of arthropathy [rheumatoid arthritis (RA) or non-RA] have been examined for their importance as determinants of synovial fluid (SF) lactate concentration in patients with knee effusions. SF lactate concentration was higher in RA than in non-RA knees. This difference was not related to the resting intraarticular pressure at the time of sampling. After drainage of SF and saline lavage of the joint, the rate of increase of lactate in a fixed volume of intraarticular saline was examined under resting conditions. The rate of increase of the lactate concentration was significantly greater in RA joints. It is most likely that SF lactate concentration under resting conditions will reflect the lactate concentration during the preceding period of activity which, in turn, is probably a composite function of the extent of synovial hypoxia due to hypoperfusion and the type of arthropathy.

Arthritis, Rheumatoid↗

PubMed1991

Separation and quantification of PGE3 following derivatization with panacyl bromide by high pressure liquid chromatography with fluorometric detection.

Separation of prostaglandin E3 (PGE3) from prostaglandin E2 (PGE2) and prostaglandin E1 (PGE1) was achieved following derivatization with p-(9-anthroyloxy)phenacyl bromide (panacyl bromide). The eicosanoid esters were analysed by reverse phase high pressure liquid chromatography with fluorometric detection (excitation 360nm and emission 470nm). Human, rat and mouse adherent cells were incubated overnight and the culture medium extracted, derivatized and analysed for PG production. PGE2 was detected from biological samples of each species tested. PGE2 synthesis was reduced when cells were incubated overnight with 5 microM eicosapentaenoic acid. PGE3 was not detectable under these experimental conditions. Studies were also undertaken using adherent cells from mice, rats and human subjects given dietary fish oil supplements rich in EPA. PGE3 production by these cells was not detected although the dietary regimens yielded substantial incorporation of EPA into cell membranes and leukocyte LTB5 production was demonstrable.

Alprostadil↗

PubMed1991

The effect of adjuvant-induced arthritis on rat leukocyte membrane phospholipid fatty acid levels following fish oil feeding.

Inflamed rats with adjuvant-induced polyarthritis showed similar incorporation of dietary eicosapentaenoic acid (EPA) into peritoneal exudate cell (PEC) membrane phospholipids compared to pair fed non-inflamed control rats. Arachidonic acid (AA) content was similar in PEC phospholipids of inflamed and control rats whereas the linoleic acid content was consistently higher in inflamed rats.

Animals↗

PubMed1991

Strategies for increasing the antiinflammatory effect of fish oil.

While both animal and human studies have shown that fish oil can exert antiinflammatory actions, the effects are modest and require large doses. The effects may be amplified by modifying the intake of other dietary fats and by making use of favourable interactions between fish oil and drugs.

Animals↗

PubMed1991

Interaction between fish and vegetable oils in relation to rat leucocyte leukotriene production.

We examined the influence of mixtures of dietary fish oil and three vegetable oils (linseed, olive and sunflower) on the incorporation of dietary eicosapentaenoic acid (EPA) into rat leucocyte phospholipids and the subsequent metabolism of EPA and arachidonic acid by 5-lipoxygenase. Eicosapentaenoic acid in leucocyte phospholipids of fish oil-fed rats was decreased by the addition of each vegetable oil to the dietary fish oil, with sunflower oil, the oil highest in linoleate (LA), having the largest EPA-lowering effect (66% decrease). The rate of synthesis of leukotriene B4 (LTB4) was increased by the addition of each vegetable oil to the basic fish oil diet, with sunflower oil having a significant effect on LTB4 synthesis (145% increase). The effects of olive oil (enriched in oleate) were similar to those of linseed oil (enriched in alpha-linolenic acid) with regard to EPA incorporation (mean decrease = 30%) and LTB4 synthesis (mean increase = 72%). The level of arachidonic acid in leucocyte membranes and the rate of synthesis of LTB4 were proportional to the level of dietary LA added to the basic fish oil diet. The results indicate that olive or linseed oil ingested in combination with fish oil have less effect than does sunflower oil on leucocyte EPA content and LTB4 production. They further suggest that, when ingested with fish oil, dietary linoleic acid is more important than oleate or alpha-linolenic acid as a determinant of these variables.

Animals↗