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Biomedical subjects

M J James

Publications and source records attributed to M J James.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Inhibition of human endothelial prostacyclin synthesis by different aspirin formulations.

The availability of different formulations of low-dose aspirin for use as anti-thrombotic agents merits a comparison of their effects on vessel wall biochemistry. We compared the effect of ingestion of an enteric-coated slow-release aspirin (Astrix) with that of soluble aspirin (Cardiprin) on human endothelial prostacyclin synthesis. Patients undergoing varicose vein surgery (10 per group) ingested 100 mg aspirin per day as Astrix or Cardiprin for 7 days prior to surgery. A control group ingested no aspirin. Prostacyclin synthesis by the endothelial surface of the great saphenous vein was determined in vitro. Both aspirin formulations caused significant inhibition of endothelial prostacyclin synthesis compared with the control group. Using the median values, the enteric-coated slow-release aspirin caused 76% inhibition, whereas the soluble formulation caused significantly greater inhibition (95%). If differential inhibition of platelet thromboxane synthesis with 'sparing' of endothelial prostacyclin synthesis is necessary for an optimum anti-thrombotic effect of aspirin, the results suggest that a lower dose of soluble aspirin than enteric-coated slow-release aspirin may be preferred.

Aspirin↗
PubMed1990

Effect of dietary oils on the production of n-3 and n-6 metabolites of leukocyte 5-lipoxygenase in five rat strains.

We examined the influence of various dietary oils, including linseed and fish oil on the relative rates of leukotriene B4 (LTB4) and LTB5 production by rat peritoneal exudate cells in five rat strains. While there was an association between the membrane phospholipid levels of the fatty acid precursors (arachidonic acid (AA) and eicosapentaenoic acid (EPA)) and the rate of synthesis of their respective 5-lipoxygenase products (LTB4 and LTB5), the rate of LTB4 synthesis was a combined function of both AA and EPA levels. We observed a strong linear relationship (correlation coefficient = 0.99) between the ratio of EPA/AA in the cell membrane phospholipids and the ratio of LTB5/LTB4 produced by these cells in vitro; this association was independent of genetic (strain) variability and was independent of the source of EPA (dietary EPA or EPA endogenously synthesized from dietary alpha-linolenic acid).

Animals↗
PubMed1990

Comparison of cell membrane phospholipid fatty acids in five rat strains fed four test diets.

The fatty acid composition of phospholipids in peritoneal exudate cells and spleen cells was assessed in five rat strains fed four test diets of differing fatty acid composition. Distinctive patterns of fatty acids were seen in the total phospholipid preparations in both cell types in response to the diets which contained either olive, sunflower, linseed or fish oil. In general, similar fatty acid profiles were seen in each of the rat strains fed the same diet with the only evidence of possible genetic (strain) variation being a relative deficiency of delta 4 desaturase in Dark Agouti rats.

Animals↗
PubMed1990

Vascular outflow resistance and angiographic assessment of lower limb arterial reconstructive procedures.

In an attempt to predict early graft occlusion secondary to poor distal run-off, the outflow resistance was measured intra-operatively and compared with the intra-operative angiogram in 50 patients undergoing lower limb bypass procedures. With arterial inflow occluded, 60 mL of plasmalyte was infused via a catheter and the resultant pressure generated in the graft was measured through a second catheter connected to a pressure transducer and recorder. Using the infusion rate and integrated pressure value, outflow resistance was calculated. High resistance measurements were defined as grafts with outflow resistance greater than 1.1 mmHg/mL per min, low measurements were defined as values less than 0.5 mmHg/mL per min and intermediate measurements were those in the range 0.5-1.1 mmHg/mL per min. Angiograms were classified independently of resistance measurements by scoring the numbers of run-off vessels crossing the ankle and stenoses, with subsequent assignment of the patient to one of three groups with either low, intermediate, or high probability of graft failure. Early graft failure was defined as cessation of graft function within 3 months of surgery. Early graft failure occurred in both cases with high outflow resistance and in seven of 44 with low outflow resistance. Of these nine occluded bypasses, six had been placed in the high probability of occlusion category on angiographic appearance and three in the intermediate category. Assessment of angiographic appearance and prediction of patency on a prospective basis had a sensitivity rate of 67% and a specificity rate of 78%. The corresponding sensitivity and specificity rates with resistance measurements were 22% and 100%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Intraarticular pressure and the relationship between synovial perfusion and metabolic demand.

We examined the influence of intraarticular pressure on products of synovial energy metabolism in patients with knee effusions. A range of intraarticular pressures was generated by controlled flexion. Pressures greater than or equal to 45 mm Hg were associated with increased synovial fluid lactate concentrations and pCO2, and decreased pH. Our results suggest that pressures greater than or equal to 45 mm Hg, which we also observed during standing and walking, can cause synovial ischemia and hypoxia manifest in a perfusion/metabolic demand mismatch. Monitoring changes in SF concentrations of uric acid did not provide consistent evidence for accelerated purine degradation following periods of inadequate perfusion. Overall, our results suggest that synovial blood flow can be compromised by modest elevations in intraarticular pressure in the range encountered during daily activity in patients with knee effusions.

Adult↗
PubMed1989

Measurement of aspirin concentrations in portal and systemic blood in pigs: effect on platelet aggregation, thromboxane and prostacyclin production.

Low doses of enteric-coated aspirin were administered orally to pigs. Plasma aspirin concentrations measured in blood obtained simultaneously from permanent catheters in a systemic artery and portal vein for 6 hours after dosage showed a large variation in the plasma aspirin concentration: time profile between pigs. After 50 mg single dose the ratio of the arterial: portal area under the plasma concentration versus time curve (AUC) was 0.63 +/- 0.08 (mean +/- SE, n = 6). In three pigs which received all three dosage regimens, the arterial: portal AUC ratios were 0.48 +/- 0.05 after 50 mg single dose, 0.52 +/- 0.02 after 100 mg single dose and 0.47 +/- 0.02 after 100 mg daily for 1 week. Platelet aggregation in response to sodium arachidonate (1.65 mM) was completely abolished after chronic aspirin administration of 100 mg daily. Thromboxane production (pg/10(6) platelets) induced by this stimulus decreased from 536 +/- 117 before aspirin to 57 +/- 14 after aspirin (mean +/- SE, n = 4; p = 0.03). Aortic prostacyclin synthesis, measured as 6-keto PGF1 alpha (ng/disc after 10 min incubation), was 1.66 +/- 0.28 (mean +/- SE, n = 4) in untreated pigs and 0.95 +/- 0.25 (n = 5) in treated pigs (p = 0.07). Results from this study support the idea that a difference between aspirin concentrations in the portal and systemic circulations can be achieved. Whether this can be translated into a clinically useful differential effect on the vessel wall compared to the platelet remains to be determined.

Animals↗
PubMed1989

Choledochoscopy via the cystic duct: evaluation of a new ultrathin disposable choledochoscope.

A 2 mm fibreoptic choledochoscope with a disposable (resterilisable) flexible section was evaluated in 25 cadavers and 13 patients undergoing cholecystectomy. It was possible to pass the instrument via the cystic duct (CD) into the common bile duct (CBD) in 23 out of 25 cadavers and in 12 out of 13 patients. The CD diameter in cadavers was 2.4 mm (SD 0.5). Optical clarity was excellent and it was easy to pass into the duodenum, but proximal passage required mobilisation of the CD/CBD junction. This instrument may be a useful adjunct or even an alternative to intraoperative cholangiography.

Common Bile Duct↗