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.

Essential fatty acids in clinical dermatology.

A deficiency of essential fatty acid intake can produce severe cutaneous abnormalities but is exceedingly rare in clinical practice. Recent research has shown that abnormalities in essential fatty acid metabolism may play a role in atopic eczema, acne, and psoriasis. Therapeutic innovations have already resulted from this knowledge, and more are likely to emerge.

Essential fatty acids and the complications of diabetes mellitus.

In animals and humans with diabetes mellitus there is evidence that normal metabolism of essential fatty acids is impaired. The main dietary essential fatty acids, linoleic acid of the n-6 series and alpha-linolenic acid of the n-3 series, must both be 6-desaturated and converted to further metabolites if they are to exert all their desirable effects on the body. 6-desaturation is impaired in diabetes and a lack of adequate rates of formation of the 6-desaturated metabolites may be involved in the abnormalities in membrane function, in lipid metabolism and in haemostasis and the microcirculatory system which are seen in diabetes.

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 prostaglandin outflow from perfused mesenteric vasculature of rats fed different fats.

The effects of dietary n-6 polyunsaturated fatty acids and replacement with saturated fat or fish oil on the prostaglandin outflow from perfused mesenteric vasculature in rats were studied. Seventy-two weanling male rats were fed ad libitum a semi-synthetic diet supplemented with 10% by weight of oil, composed wholly of n-6 fatty acid-rich evening primrose oil, or replaced partly or completely (25, 50, 75 or 100%) by n-6 fatty acid-deficient fish oil or hydrogenated coconut oil for 8 weeks. The outflows of 6-keto-PGF1 alpha, thromboxane B2, and prostaglandin E from the perfused mesenteric vasculature were measured at 60 min-time point after starting the perfusion.

Fatty acid changes in liver choline and ethanolamine glycerophospholipids in aspirin-treated rats fed linoleate, gamma-linolenate and fish oil.

The effects of dietary linoleic acid, gamma-linolenic acid and marine fatty acids on the development of aspirin-induced gastric hemorrhage and the distribution of liver glycerophospholipid fatty acids in fat-deficient growing rats were studied. Aspirin (100 mg/day)-treated and nontreated rats were fed for 7 days, a mixed diet of 2.5% safflower oil and 7.

The profile of long-chain fatty acids in serum phospholipids: a possible indicator of copper status in humans.

In previous reports of experimental copper depletion in humans, it was difficult to reliably demonstrate biochemically that there was Cu depletion. In view of the changes in serum phospholipid fatty acid profiles in Cu-deficient rats, it was considered worthwhile to determine the effect of Cu depletion in humans on serum fatty acid profiles. Serum samples from the Cu-depletion study of Reiser et al were analyzed for phospholipid fatty acid composition.

Copper intake affects rat heart performance during ischemia-reperfusion: possible relation to altered lipid and fatty acid metabolism.

Hearts from rats fed low copper (1.3 mg copper/kg diet) or a copper-supplemented diet (243 mg copper/kg diet) were perfused for 90 min according to the Langendorff method. The perfusion protocol included 30 min normoxia, 30 min ischemia and 30 min reperfusion.

Linoleic acid-induced fatty acid changes in platelet and aorta of the rat: effect of age and cholesterol.

The influence of age and cholesterol on polyunsaturated fatty acids (PUFA) levels was studied in young and old male Sprague-Dawley rats. Animals were fed a fat-free diet supplemented with 10% (by wt) safflower oil with or without 1% cholesterol for 8 wk. As a result of cholesterol feeding, proportions of linoleic acid (18:2n-6) and dihomo-gamma-linolenic acid (20:3n-6) were increased and that of arachidonic acid (20:4n-6) was decreased in the liver and platelet phospholipids in 64-wk-old rats, suggesting inhibitory effects of cholesterol on 20:4n-6 synthesis from 18:2n-6.

The influence of phenelzine and tranylcypromine on the release of prostaglandins from the rat mesenteric vascular bed.

We investigated the effects of phenelzine and tranylcypromine on the release of prostacyclin, thromboxane A2, prostaglandin E2, and prostaglandin E1 from the isolated perfused rat mesenteric vascular bed. Perfusion of the preparation with phenelzine in concentrations of 15, 45, and 135 microM for 150 min led to attenuated release of all four prostaglandins measured. Inhibition generally occurred with the lowest dose used and was most prominent with the highest concentration.

Effects of calcium deprivation on n-6 fatty acid metabolism in growing rats.

Two separate experiments examining the effects of calcium deficiency on plasma and liver fatty acids in rats were conducted. In Experiment I, weanling male Sprague-Dawley rats were fed a calcium-deficient diet with or without the supplementation of 5 or 20 g/kg calcium for 22 days. There were no significant differences in plasma and liver fatty acid distribution between the two calcium-supplemented groups.

Plasma, platelet, and aorta fatty acids composition in response to dietary n-6 and n-3 fats supplementation in a rat model of non-insulin-dependent diabetes.

Male Sprague-Dawley rats were injected with 90 mg/kg of streptozotocin at 2 days of age. After weaning, they were put on a fat-free diet supplemented with safflower oil (S), a combination of S and linseed oil (L) or a combination of evening primrose oil (E) and L for 8 weeks. Plasma glucose levels and glycosuria were significantly elevated in all 3 groups of diabetic rats in comparison with the corresponding control rats.

Prostaglandin E1: physiological significance and clinical use.

Contrary to popular belief, prostaglandin (PG) E1 and its immediate precursor, dihomogammalinolenic acid (DGLA), are found in physiologically important amounts in humans. PGE1 has many desirable effects, particularly with regard to the cardiovascular system and to inflammation. PGE1 is difficult to use therapeutically because of its short life.

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.

Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XIX. Embryonic genes.

The methylation status of a conformation-inducer protein that would effect the status of DNA in relation to its ability to be in an active or inactive state is proposed to be central in the regulation of embryonic genes. Thus a distinction can be drawn between induceable "adult" genes such as glucocorticoid induced tyrosine aminotransferase and induceable "embryonic" genes such as ethionine induced alpha-fetoprotein. However, in the proposed mechanism the methylation of DNA is also important in that a hypomethylated state of a CCGG sequence of a promotor region for a conformation-induced protein gene is required to initiate the induction events.

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.

Polyunsaturated fatty acid-induced cytotoxicity against tumor cells and its relationship to lipid peroxidation.

The contribution of lipid peroxidation to the killing of human breast cancer cells by gamma-linolenate (GLA) was examined. Other fatty acids of different cytotoxic potential containing 2, 4, 5, and 6 double bonds were also tested for comparison. It was found that the cytotoxic potential varied with the ability of the fatty acids to stimulate the production of superoxide radicals.

Differential utilization of long chain fatty acids during triacylglycerol depletion. II. Rat liver after starvation.

Rats starved for 96 hr were shown to have a 94% reduction in liver triacylglycerol. Among the long chain fatty acids in liver triacylglycerol, only stearic acid and arachidonic acid were proportionally increased (2.5 and 6 times, respectively); palmitic and linoleic acids were unchanged, and palmitoleic and oleic acids were proportionally decreased.

Differential utilization of long chain fatty acids during triacylglycerol depletion. I. Rat heart after ischemic perfusion.

Rat hearts were perfused with Krebs-Henseleit buffer for 90 min according to the Langendorff procedure. Normoxic perfusion for 90 min resulted in minor changes in fatty acid composition and a decrease in residual heart triacylglycerol to 60% of preperfusion values. When the protocol included 30 min of slow perfusion-induced ischemia, the hearts were observed to be depleted of 89% of their initial triacylglycerol content.

Changes in human plasma essential fatty acid levels as a result of administration of linoleic acid and gamma-linolenic acid.

Administration of doses of linoleic acid (LA) up to 36 g/d in humans raised blood levels of linoleic acid but not of its metabolites. This is probably because the conversion of LA to gamma-linolenic acid (GLA) is slow and rate-limiting. We have found that administration of relatively small amounts of GLA, up to 360 mg/d, raises human blood levels of dihomogammalinolenic acid (DGLA) and arachidonic acid (AA).

The role of linoleic acid and its metabolites in the lowering of plasma cholesterol and the prevention of cardiovascular disease.

An increase in linoleic acid intake lowers plasma cholesterol and is one of the safest methods for achieving this end. However, the amounts that must be consumed are large. Linoleic acid is metabolized via several routes and it is probable that a metabolite, rather than linoleic acid itself, is responsible for the cholesterol-lowering effect.

Effects of polyunsaturated fatty acids and of their oxidation products on cell survival.

The stimulatory, cytostatic and cytotoxic effects of polyunsaturated fatty acids, prostaglandins, thromboxanes, hydroperoxy fatty acids, hydroxy fatty acids and leukotrienes on normal and tumor cells are described. Their effects are related to the ability of the cells to undergo lipid peroxidation. The significance of controlled peroxidation of selected polyunsaturated fatty acids in the control of tumor development is examined.

Abnormalities of plasma and erythrocyte essential fatty acid composition in epidermolysis bullosa: influence of treatment with diphenylhydantoin.

The fatty acid composition of plasma and erythrocyte phospholipids was determined in children with various subtypes of epidermolysis bullosa (EB) and in their parents. Patients with recessive dystrophic, dominant dystrophic, simplex, or junctional forms of EB had a higher percentage composition of arachidonic acid in plasma and/or erythrocyte phospholipids compared to age-matched controls. Epidermolysis bullosa patients treated with diphenylhydantoin had lower levels of arachidonic acid in plasma and erythrocyte phospholipids than did untreated EB patients.

Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XVIII. Biomethylation and differentiation.

Many reports have appeared describing a direct relationship between hypomethylated states of genes and gene activity. Even after the introduction of viral genomes, these new genes appear to be controlled by specific DNA methylations. A variety of other studies have shown chromatin structural changes being implicated in the activities of certain gene loci.