Erythrocyte membrane docosahexaenoic acid in haemodialysis patients on epoetin.
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Animals↗
Biomedical subjects
M S Manku
Publications and source records attributed to M S Manku.
Fatty acid levels in the brains of schizophrenics and normal controls.
Essential fatty acids are important constituents of the brain. There is evidence that levels in blood of certain essential fatty acids and their eicosanoid derivatives may be abnormal. We now report that in the frontal cortex of schizophrenic patients there are significant differences from normal in the fatty acid composition of phosphatidylethanolamine. These differences from normal were not found in the cerebellar cortex.
Aged↗
Essential and other fatty acids in plasma in schizophrenics and normal individuals from Japan.
Plasma phospholipid and cholesterol ester fatty acid levels were measured in samples from normal individuals, schizophrenics, and patients with affective and paranoid disorders in Japan. The schizophrenics were divided into groups with normal and reduced platelet sensitivity to the aggregation-inhibiting effects of prostaglandin (PG) E1. As in samples from schizophrenics in several other countries, linoleic acid levels were significantly below normal, as was the ratio of linoleic acid to its metabolites. Phospholipid fatty acid levels were normal in patients with paranoid or affective disorders. When the schizophrenics were divided into those with and without an abnormal response to PGE1, oleic acid was higher and eicosapentaenoic acid lower in those patients with an abnormal response. This study lends further support to the idea that schizophrenics may differ from controls in their essential fatty acid and eicosanoid metabolism.
Adult↗
The effects of evening primrose oil, safflower oil and paraffin on plasma fatty acid levels in humans: choice of an appropriate placebo for clinical studies on primrose oil.
In a number of diseases, plasma levels of linoleic acid are normal or elevated while those of gamma-linolenic acid (18:3n-6, GLA) and further metabolites are below normal. Evening primrose oil (EPO), similar to safflower oil (SFO) except that it contains 8-9% of 18:3n-6, has been proposed as a therapeutic agent in these diseases, such as atopic eczema. There is argument as to whether an appropriate placebo for clinical studies on EPO should be an inert material such as paraffin, or a linoleic acid--containing oil such as SFO. We have therefore compared in normal humans the effects on plasma fatty acids of administering EPO, SFO and paraffin for 10 days. Paraffin had no effect on any fatty acid in any fraction. EPO raised the level of 20:3n-6 (dihomo-gamma-linolenic acid, DGLA) the immediate metabolite of GLA but had no significant effect on arachidonic acid. In surprising contrast, SFO raised the levels of linoleic and of arachidonic acids, without raising those of DGLA. This suggests that linoleic acid may be rapidly converted to arachidonic acid by a tightly linked enzyme sequence: GLA, in contrast, may be rapidly converted to DGLA but then only slowly on to arachidonic acid. These results are consistent with recent in vitro observations by others on rat hepatocytes and human fibroblasts.
Adult↗
Abnormalities of essential fatty acid distribution in the plasma phospholipids of patients with bladder cancer.
We have examined the composition of the essential fatty acids in the plasma phospholipid fractions of 98 patients with histologically proven bladder cancer. These patients were attending hospital for regular follow-up by check cystoscopy. Patients were divided into two groups, depending on the cystoscopic findings, of either active (tumour recurrence seen) or inactive (no evidence of tumour recurrence) disease. Compared with a normal population, the plasma levels of most of the fatty acids, including arachidonic acid, were significantly lower in the 98 cancer patients (P less than 0.001, t-test). We were unable, however, to demonstrate any significant differences (Mann-Whitney U-test) between the active and inactive disease groups. Plasma levels of the essential fatty acids are abnormal in patients with bladder cancer; they do not help, however, to distinguish those patients with active disease from those with inactive disease. This may arise because the deficit in essential fatty acids we have demonstrated is a predisposing factor for the development of bladder cancer rather than a metabolic consequence of the tumour. Further studies are needed to establish the possible clinical role of measurement of essential fatty acids in patients with bladder carcinoma.
Aged↗
Essential fatty acids in plasma of patients with leprosy.
We have investigated the fatty-acid composition of plasma phospholipids in 61 patients with leprosy of various clinical types with either a short or long duration of treatment. All patients had significantly decreased levels of linoleic acid and alpha-linoleic acid, the parent fatty acids of the n-6 and n-3 families, respectively. Patients with a treatment duration of more than 6 months had significantly low levels of arachidonic acid and eicosapentaenoic acid compared to controls or to patients with a treatment duration of less than 6 months. There were no differences in the fatty-acid composition between multibacillary patients and paucibacillary patients. We conclude that dietary supplementation with essential fatty acids may be indicated in patients with leprosy, particularly in those with a long treatment duration.
Arachidonic Acid↗
Age-associated reduction of prostacyclin and thromboxane synthesis is inversely related to plasma cholesterol levels: modulation by dietary cholesterol supplementation.
Abnormalities of vasoactive eicosanoid synthesis with age are reported. We observed an age-associated reduction of vascular prostacyclin production and thrombin-stimulated thromboxane A2 production in blood. Amounts of production of these eicosanoids were inversely related to plasma cholesterol levels. However, there were no such relationships in rats supplemented with cholesterol. Dietary cholesterol supplementation induced a reduction of thromboxane A2/prostacyclin ratio regardless of age. These results suggest that age-associated changes of blood cholesterol levels are closely linked with vasoactive eicosanoid synthesis and that excessive consumption of cholesterol may induce a compensatory reaction by reducing the thromboxane A2/prostacyclin ratio.
6-Ketoprostaglandin F1 alpha↗
The effects of low, medium and high dose aspirin on intimal proliferation in autologous vein grafts used for arterial reconstruction.
Bilateral femoral vein grafts were implanted in 47 adult mongrel dogs to determine the effects of aspirin on intimal hyperplasia. The animals were fed a commercially-prepared 2% cholesterol diet before and for 6 weeks following operation. Twelve animals served as the controls while the remaining animals were divided into three groups receiving low, medium, and high dose aspirin. Eleven animals received 75 mg of aspirin daily, 11 animals were fed 225 mg of aspirin daily and the remaining 13 animals received 650 mg of aspirin daily. A coagulation profile was carried out before operation and at 2, 4 and 6 weeks following operation. The grafts were harvested at 6 weeks and intimal thickness was measured with a Zeiss computerized interactive image-analyzing system. The prothrombin time, partial thromboplastin time, and platelet count were unchanged in all animals. The bleeding time was prolonged in animals receiving aspirin (P less than 0.02). Intimal thickness measured 4 +/- 0.2 microns before implantation and increased at 6 weeks to 39 +/- 5 microns in the control group. Aspirin failed to reduce intimal hyperplasia. Intimal thickness measured 37 +/- 2 microns in those animals receiving 75 mg of aspirin daily, 35 +/- 3 microns after a daily dose of 225 mg of aspirin and 51 +/- 4 microns in the high dose group receiving 650 mg of aspirin daily. Our data indicates that aspirin fails to reduce intimal proliferation in canine vein grafts which suggests that alternative or combined drug therapy may be necessary to reduce the incidence of late graft failure.
Animals↗
Essential fatty acids in plasma phospholipids in schizophrenics.
Blood samples were taken from schizophrenics and control patients in three different centers. The phospholipids were extracted from plasma and their fatty acid composition analyzed. Similar and consistent differences between schizophrenics and controls were observed at all three centers. The n-6 essential fatty acid levels were significantly reduced, whereas n-3 essential fatty acids were elevated.
Adult↗
A double-blind trial of essential fatty acid supplementation in patients with tardive dyskinesia.
This study reports the results of a trial of essential fatty acid (EFA) supplementation in psychiatric patients (predominantly schizophrenics) with movement disorders. Evidence of EFA deficiency in these patients was observed. The antidyskinetic effect of EFA supplementation was marginally significant but not clinically important. However, active treatment produced highly significant improvements in total psychopathology scores and schizophrenia subscale scores, and a significant improvement in memory.
Antipsychotic Agents↗
Premenstrual syndrome and premenstrual breast pain (cyclical mastalgia): disorders of essential fatty acid (EFA) metabolism.
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Breast↗
Plasma fatty acid levels in patients with acquired immune deficiency syndrome and in controls.
Polyunsaturated fatty acids (PUFAs) are known to modulate the immune system in vivo and to inactivate envelope viruses in vitro. Patients with AIDS had low total plasma lipid levels and low levels of a number of individual fatty acids. However, the C20 and C22 essential fatty acids of the n-3 series were selectively and highly significantly reduced. Normalization of these fatty acid levels in AIDS patients may be a worthwhile therapeutic aim.
Acquired Immunodeficiency Syndrome↗
Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and clinical response.
Gamma-linolenic acid in the form of a particular variety of evening primrose oil (Epogam) has been reported of value in the treatment of atopic eczema. Nine controlled trials of evening primrose oil were performed in eight centres. Four of the trials were parallel and five cross-over. Doctors and patients assessed the severity of eczema by scoring measures of inflammation, dryness, scaliness, pruritus and overall skin involvement. Individual symptom scores were combined to give a single global score at each assessment point. In the analysis of the parallel studies, both patient and doctor scores showed a highly significant improvement over baseline (P less than 0.0001) due to Epogam: for both scores the effect of Epogam was significantly better than placebo. Similar results were obtained on analysis of the cross-over trials, but in this case the difference between Epogam and placebo in the doctors' global score, although in favour of Epogam, failed to reach significance. The effects on itch were particularly striking. There was no placebo response to this symptom, whereas there was a substantial and highly significant response to Epogam (P less than 0.0001). When the improvements, or otherwise, in clinical condition were related to changes in plasma levels of dihomogammalinolenic and arachidoni acids, it was found that there was a positive correlation between an improvement in clinical score and a rise in the fatty acid levels.
Adolescent↗
Effects of low-dose marine oils on intimal hyperplasia in autologous vein grafts.
The effects of low-dose cod-liver oil on intimal hyperplasia of vein grafts were examined in 45 adult mongrel dogs undergoing peripheral arterial reconstruction. Fifteen animals served as the control group, 15 animals were fed a fish-oil supplement containing 240 mg of eicosapentaenoic acid daily, and a further 15 animals received 480 mg of eicosapentaenoic acid daily. Segments of undistended external jugular vein were anastomosed to bilaterally divided femoral arteries. The grafts were harvested at 6 weeks and intimal thickness was measured with a computerized interactive image analyzing system. Serum cholesterol level, prothrombin time, partial thromboplastin time, bleeding time, and platelet counts were measured before the operation and at 2, 4, and 6 weeks after the operation. Plasma levels of thromboxane B2 and prostaglandin F1 alpha and serum levels of eicosapentaenoic acid were measured before and 4 weeks after the operation. Serum cholesterol level increased similarly and significantly in all animals. Serum levels of eicosapentaenoic acid rose proportionately with the oral ingestion of fish oil but did not affect coagulation parameters. Plasma thromboxane B2 and prostaglandin F1 alpha were not significantly affected by the ingestion of marine oils. Intimal thickness was 39 +/- 5 microns in the control dogs. Ingestion of 240 mg of eicosapentaenoic acid reduced intimal thickness to 24 +/- 3 microns at 6 weeks (p less than 0.01). Increasing the dose by a factor of 2 did not decrease intimal thickness further, the intima being 23 +/- 2 microns (p less than 0.005). Our data indicate that small doses of fish oil will reduce intimal proliferation in autologous vein grafts and that marine oils may exert their beneficial effects on intimal hyperplasia by a mechanism other than their known effects on prostanoid metabolism.
Animals↗
Effects of low magnesium diet on the vascular prostaglandin and fatty acid metabolism in rats.
Deficiency of magnesium with cardiovascular effects is thought to be related to alterations in the biosynthesis of prostaglandins (PGs) in the vasculature. Measurements were made of the PGE2, 6-keto-PGF1 alpha and thromboxane B2 (TxB2) outflow from the perfused isolated mesenteric arterial bed and the fatty acid composition of the tissue in rats maintained for 14 weeks on a low magnesium (LMg) diet. The serum Mg levels were significantly decreased and the serum Ca levels were significantly increased in the LMg group as compared to the controls. The arachidonic acid concentration in the triacylglyceride fraction was significantly increased in the LMg group. Long chain polyunsaturates such as 22:4n6 and 22:6n3 were consistently increased in the LMg rats as compared to the controls in both the phospholipid and triglyceride fractions as previously reported in other tissues. The PGE2, 6-keto-PGF1 alpha and TxB2 outflows were significantly increased in the LMg group as compared to the controls. These findings suggest that the biosynthesis of eicosanoids, mainly PGI2, is stimulated in Mg deficiency, and this may provide protection against intracellular Mg depletion and Ca accumulation, so as to counteract to the constricted and hyperreactive state of the vasculature in such a condition.
Animals↗
Effects of albumin on fatty acid, protein, and eicosanoid levels in rat mesenteric arterial bed perfusions.
Male rats were maintained on rat chow supplemented with 5% evening primrose oil for 2 weeks. Mesenteric perfusions were then performed, half with and half without albumin. Albumin was found to increase the yield of fatty acids and reduce eicosanoid levels. Perfusions without albumin decreased fatty acid release, increased eicosanoid levels, and showed a decrease in protein concentration over time. The value of albumin as a "trap" for fatty acids during perfusion experiments depends upon what parameter is to be measured.
Albumins↗
Release of fatty acids by perfused vascular tissue in normotensive and hypertensive rats.
The release of fatty acids from perfused mesenteries of spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) was studied. The release of the prostaglandin precursors dihomogammalinolenic acid, arachidonic acid, and eicosapentaenoic acid was reduced in SHR when compared with age-matched WKY. The release of all other fatty acids detected in the effluent was also reduced. The differences in fatty acid release were evident even when tissue levels of the fatty acids were similar or higher in SHR than in controls. The addition of evening primrose oil and fish oil into the diet partially corrected these defects. Evening primrose oil and fish oil both attenuated increases in blood pressure, but fish oil was more potent than primrose oil. Although both diets reduced vascular reactivity, primrose oil was more effective with lower doses of norepinephrine whereas fish oil blunted the effects of both low and high doses of norepinephrine. The possible mechanisms for the effects of primrose oil and fish oil on vascular reactivity are briefly discussed.
8,11,14-Eicosatrienoic Acid↗
Double blind cross-over trial with fenfluramine.
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Autistic Disorder↗