Double blind cross-over trial with fenfluramine.
Explore the source record for details and available documents.
Autistic Disorder↗
Biomedical subjects
M S Manku
Publications and source records attributed to M S Manku.
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).
Adult↗
Plasma phospholipid essential fatty acids and prostaglandins in alcoholic, habitually violent, and impulsive offenders.
Plasma phospholipid essential fatty acids and some of their main metabolites, prostaglandins, were measured among habitually violent and impulsive male offenders, who all had alcohol abuse problems, and nonviolent control persons. Linoleic acid (18:2n-6), the precursor of the n-6 fatty acids, was below normal in intermittent explosive disorder, but the dihomogammalinolenic acid (DGLA) (20:3n-6) and some subsequent n-6 acids were at the same time elevated among all offenders. Also, a monounsaturate, oleic acid (18:1n-9) was elevated. The high DGLA correlated with low cholesterol level in intermittent explosive disorder. The arachidonic acid metabolites PGE2 and TxB2 were elevated in violent antisocial personality. The PGE1/DGLA ratio was low in intermittent explosive disorder. The number of registered violent crimes and violent suicidal attempts correlated with high phospholipid DGLA values. The possibility that the high phospholipid DGLA is connected with low free DGLA pool, and therefore low PGE1 formation, among these offenders is discussed.
8,11,14-Eicosatrienoic Acid↗
The influence of dietary marine oil (Polepa) and evening primrose oil (Efamol) on prostaglandin production by the rat mesenteric vasculature.
The interactions of n-6 and n-3 fatty acids on prostaglandin metabolism in the isolated rat mesenteric vessels were studied. Sprague-Dawley rats (200-220 g) were fed for two weeks a fat-free semi-synthetic diet supplemented with 10% by weight of different combinations of Evening Primrose Oil (Efamol), a rich source of linoleic acid (LA) and gamma-linolenic acid (GLA), the immediate precursor of dihomo-gamma-linolenic acid (DGLA), and Polepa (POL), a marine oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. The combinations of supplement were as follows: 9% Efamol - 1% POL, 8% Efamol - 2% POL, 7% Efamol - 3% POL, 6% Efamol - 4% POL, 5% Efamol - 5% POL. The outflow of thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), PGE2, and PGE1 was decreased in relation to the proportion of marine oil in the diet, except for the group which received 8% Efamol - 2% POL, and which showed an increase in 6-keto-PGF1 alpha, PGE2, and PGE1. The decrease in TxB2 was much greater than those of 6-keto-PGF1 alpha or PGE2, while PGE1 followed the same pattern as prostacyclin and PGE2. These results suggest that n-3 fatty acids, at high concentrations, inhibits conversion of both DGLA and AA to eicosanoids. Low concentrations of fish oil may, in contrast, increase formation of desirable 1 and 2 series eicosanoids.
Administration, Oral↗
Impaired platelet aggregation and thromboxane generation in essential fatty acid-deficient rats.
ADP-induced platelet aggregation and thrombin-induced thromboxane B2 generation in diluted whole blood from rats fed a fat-free diet supplemented with 10% (by weight) hydrogenated coconut oil [essential fatty acid (EFA) deficient] were significantly lower than that in animals fed 10% safflower oil [(SFO) rich in linoleic acid] or 10% marine oil (rich in eicosapentaenoic acid and docosahexaenoic acid). Plasma fibrinogen levels were significantly lower and liver function was impaired in the EFA-deficient group compared with the other two groups. Platelet responsiveness to ADP was restored when plasma from the EFA-deficient rats was replaced by plasma obtained from rats fed a nonpurified diet. ADP responsiveness and thrombin-stimulated thromboxane B2 production in diluted whole blood were also restored after 2 wk of injections of 100 mg ethyl linoleate every 48 h, and partially restored by injections of 100 mg ethyl alpha-linolenate. When ADP-induced platelet aggregation was examined in washed platelets, the impaired ADP aggregation (found when platelets of the EFA-deficient rats were suspended in their own plasma) was not observed at either high (9.5 microM) or low (1.0 microM) ADP concentrations. Although thrombin-stimulated thromboxane B2 production in washed platelets in the EFA-deficient rats was lower than that in the SFO-fed rats, the magnitude of aggregation was not different. In addition, inhibition of thrombin-induced platelet aggregation by apyrase (0.06 U/mL) was identical in the two groups. These results suggest that impaired platelet aggregation in EFA deficiency is related more to plasma factors than to inherent platelet properties and that restoration of normal liver function is associated with normal platelet function.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Diphosphate↗
Essential fatty acids in the plasma phospholipids of patients with atopic cataracts.
Abnormal levels of the essential fatty acids (EFA) in plasma phospholipids have been reported in atopic dermatitis. We have compared EFA levels in 10 patients with atopic cataracts and 29 atopic dermatitis patients without cataracts and found no significant differences, with the exception that higher levels of adrenic acid occurred in those with cataracts.
Adult↗
Triacylglycerol content of arachidonic acid varies inversely with total triacylglycerol in liver and plasma.
In both liver and plasma from rats, hamsters, guinea pigs and monkeys, the correlation coefficients between percentage composition of arachidonic acid and the total triacylglycerol varied from -0.43 to -0.81 (P less than 0.01). No such relationship was present between percentage compositions of any of the essential fatty acids in phospholipids and total phospholipids.
Animals↗
Altered arachidonic acid content in polymorphonuclear and mononuclear cells from patients with allergic rhinitis and/or asthma.
We previously have found that monocytes from patients with allergic rhinitis and/or asthma produce less PGE2 than cells from normal subjects in response to a histamine-induced lymphokine. In order to investigate this observation further, we measured the fatty acid content in the total phospholipids derived from the plasma, red cells, buffy coat cells, neutrophils, monocytes and lymphocytes of 27 allergic patients and 21 normal controls. There were no substantial differences between atopics and normals in the fatty acid analyses carried out for plasma and red cells. However, linoleic acid (18:2n-6) levels were elevated significantly in the buffy coat fraction, while arachidonic acid (20:4n-6) levels were reduced. Measurement of fatty acid levels after fractionation of the buffy coat population into neutrophils and monocytes yielded similar elevations in 18:2n-6 and reduced 20:4n-6. In contrast, lymphocytes appeared to have the reverse pattern, i.e., significantly reduced 18:2n-6 and elevated 20:4n-6 levels. These data suggest that atopic leukocytes may have altered essential fatty acid metabolism.
Adolescent↗
The influence of dietary manipulation with n-3 and n-6 fatty acids on liver and plasma phospholipid fatty acids in rats.
The interrelations between linoleic acid (LA) metabolites and fish oil fatty acids were studied. Sprague-Dawley rats (200-220 g) were fed a fat-free semisynthetic diet supplemented with 10% (by weight) of different combinations of evening primrose oil (EPO), a rich source of LA and gamma-linolenic acid, and polepa (POL), a marine oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. The combinations of supplement were as follows: 9% EPO-1% POL, 8% EPO-2% POL, 7% EPO-3% POL, 6% EPO-4% POL and 5% EPO-5% POL. After two weeks on the respective diets, the animals were killed, and the fatty acid compositions of liver and plasma phospholipids were examined. The results showed that animals fed higher proportions of POL consistently contained higher levels of dihomo-gamma-linolenic acid (DGLA) (p less than 0.05), a metabolite of LA and GLA, and lower levels of arachidonic acid (AA) (p less than 0.01), a metabolite of DGLA through delta-5-desaturation. Thus, an inverse relationship between AA/DGLA ratio and EPA levels was found to exist (r = -0.765 in plasma and -0.792 in liver). However, there was no such relationship between AA/DGLA ratio and DHA levels. This result suggested that EPA but not DHA in fish oil exerts an inhibitory effect on the conversion of DGLA to AA.
Animals↗
Increased release of prostaglandins from the mesenteric vascular bed of diabetic animals: the effects of glucose and insulin.
To study prostaglandin (PG) metabolism in peripheral vascular beds, PGs and TxB2 released from perfused mesenteric tissues were measured in both normal and streptozotocin (STZ)-induced diabetic rats. The release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) was significantly increased in mesenteric vascular beds from diabetics in comparison with control rats. The 6-keto-PGF1 alpha/TxB2 ratio was decreased in diabetics. In order to clarify the mechanism of this imbalanced synthesis of eicosanoids, we infused buffer with 500 mg/dl glucose which was similar to the concentration of blood glucose in the diabetic rats. In response to this high glucose concentration, TxB2 released into the effluent from the mesenteric beds of normal animals was increased to the diabetic level. The release of the other PGs was not changed significantly. The 6-keto-PGF1 alpha/TxB2 ratio was decreased in control rats perfused with buffer containing 500 mg/dl glucose. We also investigated the effect of insulin (50 and 100 microU/ml) in the diabetic mesenteric vascular beds, but there were no changes in prostaglandin or TxB2 release. These data suggest that a high glucose level may have an important role in regulating TxA2 synthesis and in modulating the balance between PGI2 and TxA2 in diabetes. It is postulated that an increase in the micro-circulation of PGI2 may partially be protective against the progression of angiopathy.
6-Ketoprostaglandin F1 alpha↗
Influence of different dietary fatty acid sources on erythrocyte lipids and plasma and liver essential fatty acids in hamsters fed ethanol.
Hamsters fed ethanol were given three different dietary sources of essential fatty acids; safflower oil, evening primrose oil (both mainly n-6 fatty acids) or linseed oil (mainly n-3 fatty acids). After 7 weeks, plasma, erythrocyte and liver lipids and fatty acids were analyzed. Plasma and liver lipids were not significantly different in the ethanol-fed hamsters compared to the controls. Erythrocyte total phospholipid was increased only in the ethanol-fed groups given n-6 but not n-3 fatty acids. Some fatty acid changes induced by ethanol were predictable, e.g. lower 20:4 n-6 in hamsters fed n-6 fatty acids, but others were not predictable, e.g. higher 22:6 n-3 in all the ethanol-fed groups. The effect of ethanol on hamster lipids and fatty acid composition appears dependent on the predominant class of dietary fatty acids.
Alcohol Drinking↗
Effects of dietary saturated, N-6 and N-3 polyunsaturated fats on blood pressure and prostaglandins outflow from perfused mesenteric vascular bed in rats.
Effects of the dietary administration of saturated fat and of n-6 and n-3 polyunsaturates on blood pressure, prostaglandin metabolism in small vessels, tissue fatty acid distribution and urinary PGE2 excretion were compared. Rats were divided into three groups. Diets contained 10% hydrogenated coconut oil (HCO), 10% safflower oil (SFO) or 10% cod liver oil (CLO) added to a basic fat free diet for 10 weeks. Systolic blood pressure was increased in the CLO group animals. Urinary PGE2 excretion was decreased in the HCO and CLO groups as compared to that in the SFO group animals. PGE2, 6-keto-PGF1 alpha and thromboxane (Tx) B2 outflow from isolated perfused mesenteric arterial beds were extremely decreased in the CLO group animals, and to a lesser extent in the HCO group as compared to the SFO animals. In the tissue phospholipid, 20:3n-9/20:4n-6 ratios were increased in the HCO group indicating essential fatty acid deficiency, and n-6 and n-3 polyunsaturates were elevated in the SFO and the CLO group animals respectively. Arachidonic acid concentration was highest in the SFO group, while there was no significant differences between the HCO and the CLO group. These results suggest that dietary fatty acid manipulation affects urinary PGE2 excretion and PGI2, PGE2 and TxA2 synthesis in mesenteric arterial beds and also changes the tissue fatty acid distribution. Furthermore, n-3 polyunsaturates caused an extreme reduction of 2-series PGs synthesis in small resistance vessels.
Animals↗
Prostaglandins and thromboxane outflow from the perfused mesenteric vascular bed in spontaneously hypertensive rats.
To clarify the metabolism of PGE2, prostacyclin (PGI2) and thromboxane A2 (TxA2) in small vessels in spontaneously hypertensive rats (SHR), we removed superior mesenteric vascular beds from 10 week old SHR and age matched normotensive controls (WKY). The mesenteric artery was perfused with Krebs-Henseleit buffer and samples of effluent collected every 15 minutes during 3 hours perfusion for analysis of PGE2, 6-keto-PGF1 alpha (a stable metabolite of PGI2) and TxB2 (a stable metabolite of TxA2) by specific radioimmunoassays. Levels of all three arachidonic acid (AA) metabolites, PGE2, 6-keto-PGF1 alpha and TxB2, in the mesenteric effluent were significantly reduced in SHR as compared to WKY. TxB2 was detected in all samples throughout the perfusion. 6-keto-PGF1 alpha/PGE2 ratios and TxB2/PGE2 ratios were significantly increased in SHR. 6-keto-PGF1 alpha/TxB2 ratios in the first four samples were significantly decreased in SHR as compared to WKY. These data suggest that there may be reduced availability of PG precusor AA and unbalanced synthesis of PGs in small vessels in SHR. Both may have relevance to the development of hypertension in the animals.
Animals↗
Plasma essential fatty acids in pure and mixed race American Indians on and off a diet exceptionally rich in salmon.
Eskimos on a traditional diet have unusually low prevalences of cardiovascular disease and cancer. One possible reason is the high intake of eicosapentaenoic acid (EPA) which is thought to account for the high EPA and low arachidonic acid (AA) levels in Eskimo plasma. People who also consume a traditional diet exceptionally rich in EPA are the Indians of the west coast of Vancouver Island. There are about 12,000 of these people and their traditional diet has been affected much less than that of the Eskimos. When on their traditional diet the Vancouver Island Indians, like the Eskimos, have high EPA and low AA levels in plasma. When eating European food, EPA levels are in the European range, but AA levels are still exceptionally low, a finding also reported from Eskimos living in Denmark. In a small mixed race group, AA levels were intermediate between those in pure Indians and in Europeans. The high EPA levels in Eskimos and West Coast Indians are related to diet. The low AA levels, in contrast, are probably genetically determined. Unusual disease patterns in these populations cannot be entirely attributed to diet.
Adult↗
Essential fatty acids in the liver and adipose tissue of genetically obese mice: effect of supplemental linoleic and gamma-linolenic acids.
Genetically obese mice (ob/ob) and their lean litter-mates were given diets iso-energetically supplemented with sucrose, hydrogenated coconut oil, safflower oil or evening primrose (Oenothera biennis) oil. Weight gain over 15 weeks was significantly greater in the evening primrose oil-supplemented obese mice than in the other groups. In all the groups of obese mice, liver total phospholipids contained proportionally less linoleic acid and more dihomo-gamma-linolenic acid and arachidonic acid than did the lean controls. As a percentage of total fatty acids, n-3 essential fatty acids (EFA) in liver and adipose tissue lipids were significantly lower in the obese mice than in the lean controls. Supplementation with EFA-rich oils (safflower and evening primrose oil) increased the proportional composition of n-6 EFA and decreased the n-3 EFA more in the liver total phospholipids of the lean than the obese mice.
Adipose Tissue↗
Abnormal essential fatty acid composition of tissue lipids in genetically diabetic mice is partially corrected by dietary linoleic and gamma-linolenic acids.
Genetically diabetic mice (db/db) and their non-diabetic litter-mates were maintained for 15 weeks on diets supplemented with safflower oil or evening primrose (Oenothera bienis) oil, both essential fatty acid (EFA)-rich sources, or hydrogenated coconut oil (devoid of EFA). Plasma glucose was higher in the diabetic mice supplemented with the oils than in the unsupplemented diabetic mice. In the oil-supplemented non-diabetic mice, plasma glucose did not differ compared with the unsupplemented non-diabetic mice. The proportional content of arachidonic acid in the phospholipids of the pancreas was significantly decreased in diabetic mice, an effect which was completely prevented by supplementation with safflower or evening primrose oil but not hydrogenated coconut oil. In the liver phospholipids of the diabetic mice, dihomo-gamma-linolenic acid was proportionally increased, an effect reduced by supplementation with safflower oil but not evening primrose or hydrogenated coconut oils. In the liver triglycerides of the diabetic mice, gamma-linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid were all proportionally decreased, effects which were also prevented by safflower or evening primrose oil but not hydrogenated coconut oil. Alopecia and dry scaly skin were prominent in the diabetic mice but less extensive in the diabetic mice supplemented with EFA.
Animals↗
Spontaneous bilateral malignant glaucoma.
A case of spontaneous bilateral malignant glaucoma is described. There was no history of antecedent eye disease of any kind and the patient had not been on any ocular therapy. The condition resolved completely with conservative treatment.
Acetazolamide↗
The effects of hydrogenated coconut oil, safflower oil, and evening primrose oil on development of hypertension and sodium handling in spontaneously hypertensive rats.
Spontaneously hypertensive rats (SHR) were fed a basal regular diet (BD) or three different fat-supplemented diets which contained 10% hydrogenated coconut oil (HCO), 10% safflower oil (SFO), or 10% evening primrose oil (EPO). The rats received these four different diets from 4 weeks to over 24 weeks of age. The development of hypertension in SHR was significantly retarded in the EPO-supplemented animals. The blood pressure was lower in the SFO group animals as compared with the BD and HCO groups, but this did not reach significance. Sodium excretion rate in young SHR was increased in the EPO group compared with the HCO and SFO groups, and the urinary K/Na ratio was decreased in the EPO group compared with the HCO and EPO groups. Water intake and urine volume were increased in the SFO group as compared with the HCO and EPO groups. Sodium concentration in erythrocytes was decreased in the rats receiving SFO. Pressor responses to norepinephrine and angiotensin II were enhanced in the EPO and SFO groups as compared with the basal chow group. These data suggest that a dietary supplementation of EPO which contains a substantial amount of gamma-linolenic acid consistently lowers blood pressure in SHR. The mechanism is uncertain, but the effects on sodium handling may in part be responsible for the retardation of the development of hypertension. There was a difference between the EPO and the SFO groups in sodium--water handling, and to some extent in the blood pressure development in SHR.
Angiotensin II↗