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D F Horrobin

Publications and source records attributed to D F Horrobin.

At least 19 recordsLinked to original sources
PubMed1992

Effect of n-3 and n-6 fatty acids on hepatic microsomal lipid metabolism: a time course study.

The present study examines the time dependent effects of n-6 and n-3 polyunsaturated fatty acids on liver microsomal lipid metabolism in FVB mice fed a diet supplemented with a mixture of free fatty acids (mainly 18:3n-6 and 20:5n-3) at 25 mg/g diet. Significant changes in the fatty acid composition of total liver and microsomal lipids were observed after 7 days on the diets. Thereafter, some animals remained on the same diet while others were fed a diet supplemented with hydrogenated coconut oil (HCO). With the exception of 20:5n-3 which showed a slower recovery, establishment of the HCO pattern was rapid indicating that the diet-induced changes could be easily reversed. The unsaturation index, the cholesterol/phospholipid ratio and the microviscosity of the microsomal membranes were not affected by these dietary manipulations. Unsaturated fatty acid supplementation reduced the activity of delta 9 desaturase by 50%. Feeding the HCO diet to mice previously fed the EPA/GLA diet led to a progressive increase in delta 9 desaturase activity, reaching 80% of the day zero values after 14 days. The monoene content of hepatic total lipids reflected, in most cases, the changes in enzyme activity. This study shows that a low dose of a n-3 and n-6 free fatty acid mixture increases the quantities of members of the n-3 family, without loss of n-6 fatty acids in microsomal membranes and modifies the activity of delta 9 desaturase without altering the microsome physicochemical parameters.

Animals↗
PubMed1992

The use of gamma-linolenic acid in diabetic neuropathy.

EF4 is an entirely new approach to the management of diabetic neuropathy. EF4 (providing gamma-linolenic acid or gamolenic acid, GLA) has been shown to reverse existing diabetic neuropathy in trials in seven centres. Diabetic animals and humans have a reduced ability to convert dietary linoleic acid to GLA. GLA and its metabolites are required for normal neuronal structure and function and a normal microcirculation. The lack of GLA and its metabolites may play a major role in the development of the neuropathy. EF4 helps to correct the biochemical defects, restores levels of GLA metabolites towards normal and produces highly significant clinical and neurophysiological improvements in diabetic neuropathy.

Animals↗
PubMed1992

The relationship between schizophrenia and essential fatty acid and eicosanoid metabolism.

Essential fatty acids (EFAs) and their eicosanoid derivatives are important constituents of the brain and regulators of neuronal function. There is direct and indirect evidence of impaired metabolism of prostaglandin (PG)E1 in schizophrenia. There is also direct evidence of abnormal EFA biochemistry with plasma phospholipids from five populations and brain phospholipids from another all showing reduced levels of linoleic acid and elevated levels of 22-carbon EFAs of both n-6 and n-3 series. Clinical trials of PGE1 and of the PGE1 precursors, gamma-linolenic acid (GLA) and dihomo-gamma-linolenic acid (DGLA) have shown modest therapeutic effects. In view of lack of therapeutic process involving drugs based on the dopamine concept of schizophrenia, it is time for new approaches based on the EFA/PG concept to be evaluated thoroughly.

Alprostadil↗
PubMed1992

Effects of cholesterol on viability and (n - 6) fatty acid metabolism in cultured human monocyte-like cells (U937).

Effects of supplementation of growth-promoting cholesterol on metabolism of the cytotoxic (n - 6) polyunsaturated fatty acids in cultured human monocyte-like cells (U937) have been examined. U937 cells were incubated in 5% delipidated fetal bovine serum containing 0 or 38.7 microM cholesterol. The rate of uptake and the distribution of metabolites of (n - 6) fatty acids (such as 18:2(n - 6), 18:3(n - 6), and 20:3(n - 6), and 20:4(n - 6)) were examined by adding radiolabelled fatty acid at a level of 1 microgram/mL (3.3 microM for 20-carbon fatty acids and 3.6 microM for 18-carbon-fatty acids). For assessing the cytotoxicity, (n - 6) fatty acids were added to medium at a concentration of 5 micrograms/mL (16.4 microM for 20-carbon fatty acids and 17.9 microM for 18-carbon fatty acids). Cholesterol supplementation suppressed the uptake of all (n - 6) fatty acids and reduced the cytotoxic effects of 18:2(n - 6), 20:3(n - 6), and 20:4(n - 6), but not 18:3(n - 6). In addition, cholesterol supplementation increased peroxide production and metabolism of (n - 6) fatty acids in U937 cells. Thus, the differential suppressive effect of cholesterol on the cytotoxicity of different fatty acids could not be attributed to an inhibitory effect on fatty acid delta 6- and delta 5-desaturation, or to an antioxidant effect on peroxide formation.

Cell Death↗
PubMed1979

Mind and cancer.

Explore the source record for details and available documents.

Animals↗
PubMed1979

Schizophrenia: Reconciliation of the dopamine, prostaglandin, and opioid concepts and the role of the pineal.

In recent years it has been suggested that the biological defect in schizophrenia may be related to excess dopamine activity, to production of an abnormal opioid or a normal opioid in excess, to a prostaglandin deficiency, to a hypersensitivity to wheat proteins, to an allergic phenomenon, to a defect in zinc metabolism, or to a pineal deficiency. The present hypothesis proposes that the various concepts are not mutually exclusive but represent different aspects of the same problem. The final common path in schizophrenia may be a failure of formation and action of prostaglandins of the 1 series.

Allergens↗
PubMed1979

Progesterone interferes with the actions of prostaglandin (PG) E1 but not those of PGE2 or PGF2 alpha in a rat vascular preparation.

In the mammary gland some actions of prolactin seem mediated by PGs. Progesterone blocks several of the mammary effects of prolactin. We therefore investigated the effects of 100 ng/ml progesterone (within the normal human plasma concentration in pregnancy) on the vascular effects of PGE2, PGEF2 alpha and PGE1. Progesterone had no effects on the responses to PGE2 and PGF2 alpha but significantly (p less than 0.01) attenuated the actions of low concentrations of PGE1. It may have enhanced the actions of high PGE1 concentrations. Progesterone appears able to block some effects of PGE1 and to imitate others.

Animals↗
PubMed1979

Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. I. Effects of ethanol.

Ethanol, over the concentration range 33 to 300 mg/100 ml (7.2-65.2 x 10-3 M) caused a dose dependent and highly significant enhancement of conversion of 14C-dihomogammalinolenic acid (DGLA) to prostaglandin (PG) El and to thromboxane (Tx) B1 by human platelets. Ethanol had no significant effect on conversion of 14C-arachidonic acid to PGE2 and TxB2. This concentration range is the one involved in human alcoholic intoxication. The effect could be related to enhanced transport of DGLA to the active site of the cyclo-oxygenase enzyme complex, to a modification of the enzyme complex which changes the way it metabolizes DGLA but not arachidonic acid or to two different enzymes. Whatever the mechanism it seems that it is possible to regulate selectively the formation of 1 and 2 series PGs probably at the cyclo-oxygenase level. The physiological and clinical implications of this are discussed.

8,11,14-Eicosatrienoic Acid↗
PubMed1979

Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. II. Effects of vitamin C.

Vitamin C over the concentration range 10 to 100 microgram/ml (5.7-57 x 10-5 M) caused a dose dependent and highly significant enhancement of conversion of 14C-dihomogammalinolenic acid (DGLA) to prostaglandin (PG) E1 and to thromboxane (Tx) B1 by human platelets. Vitamin C had no effect on conversion of 14C-arachidonic acid to PGE2 and TxB2. The concentration range is relevant to physiology: in some cells which concentrate the vitamin, such as polymorphonbuclear leucocytes and the adrenal cortex, vitamin C concentrations may be substantially higher than 100 microgram/ml. Vitamin C can therefore selectively enhance the formation of cyclo-oxygenase generated products from DGLA without changing formation of those from AA. This effect can account for a number of the known actions of vitamin C including its effect on the immune system. The implications of this finding are discussed.

8,11,14-Eicosatrienoic Acid↗
PubMed1979

Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil.

Multiple sclerosis (MS) is a disease with no known treatment. In view of this and of its distressing nature patients are attracted by any new concepts. As a reaction to this neurologists are sometimes excessively sceptical and fail to consider new approaches seriously. Recent attempts have been made to treat multiple sclerosis with polyunsaturated fatty acids and with colchicine. This approach is not arbitrary and is firmly grounded in fundamental basic scientific concepts. In patients with multiple sclerosis there is evidence of both an abnormality in essential fatty acid metabolism and an abnormality in lymphocyte function. It is now apparent that the fatty acid abnormality may cause the lymphocyte abnormality and that both may be improved by dietary manipulation. There is also evidence that the demyelination may be associated with recurrent inflammatory episodes and with entry of calcium into the cytoplasm. In vitro colchicine has been shown to have actions compatible with regulation of cytoplasmic calcium and in two diseases characterised by intermittent inflammatory episodes (Behçets syndrome and familial Mediterranean fever) it has been found to prevent or to reduce the severity of such episodes. Preliminary results suggest that combined therapy with evening primrose oil and colchicine may be of considerable value.

Behcet Syndrome↗
PubMed1979

The nutritional regulation of T lymphocyte function.

Prostaglandin (PG) E1 plays a major role in the regulation of thymus development and T lymphocyte function and the evidence for this is reviewed. The production of PGE1 is dependent on nutritional factors with linoleic acid, gamma-linolenic acid, pyridoxine, zinc and vitamin C playing key roles. Inadequate intake of any one of these will lead to inadequate PGE1 formation and defective T lymphocyte function. Megadoses of any one are likely to be only minimally effective in the absence of adequate intakes of the others. By careful attention to diet it should be possible to activate T lymphocyte function in the large number of diseases including rheumatoid arthritis, various auto-immune diseases, multiple sclerosis, and cancer in which such function is defective. It is possible that T lymphocytes may require both endogenous and exogenous PGE1 in order to function adequately. It is therefore of particular interest that many cancer cells and virally infected cells are unable to make PGE1 because they cannot convert linoleic acid to gamma-linolenic acid. The direct provision of gamma-linolenic or dihomo-gammalinolenic acids in these situations is worthy of full investigation.

Animals↗