Search

Might doctors performing the study have been given the wrong injection instructions? EDITOR--I was surprised to read the letter from Robert Dow, chief executive of Scotia, stating that Foscan (temoporfin), [...]

Preliminary evidence suggests beneficial effects of pure ethyl-eicosapentaenoate (ethyl-EPA) in Huntington disease (HD).

Wheat grain cooking involves heating and moisture uptake. Stapley et al. (Int. J. Food Sci. Technol. 1997, 32, 355) documented the differences between moisture uptake in boiled and steamed grains. The relationship and coupling between the heat- and mass-transfer processes is investigated here. By determining the moisture−activity diagram arising from the Stapley et al. steaming data (Chem. Eng. Sci. 1999, 54, 965), it is argued for the first time that heat transfer exerts the key controlling influence on the moisture mass transfer in steaming. A heat- and mass-transfer model for grain steaming is developed that extends and improves on the previous model (Chem. Eng. Sci. 1999, 54, 965). This model allows for the coupling of the two processes and the introduction of a dimensionless parameter, as well as providing neater solutions. In steaming, the observed temperature elevation in the grain suppresses the driving force for mass transfer. This study contributes to a better understanding of the cooking operation and will lead to improvements in batch cooking operations in breakfast cereal manufacturing.

The effect of n-6 fatty acids, particularly y-linolenic acid (GLA), on the oxidase response and neutrophil priming by tumour necrosis factor a and interleukin 8 was studied in both normal volunteers and patients with obstructive jaundice. GLA inhibited the neutrophil respiratory burst at concentrations higher than 50 μmol/l, but abolished cytokine priming at concentrations as low as 1 μmmol/1. Inhibition was not the result of either cytotoxicity to the neutrophils or alteration in cytosolic free calcium homoeostasis. It is concluded that GLA is a potential inhibitor of neutrophil priming by cytokines and of the oxidative response.

Zinc deficiency and essential fatty acid deficiency in rats have gross effects which are very similar. Zinc, prostaglandin E1, and dihomo-γ-linolenic acid (prostaglandin E1precursor) all have very similar effects on rat vascular smooth muscle. Zinc deficiency has no consistent effect on tissue zinc or zinc enzymes. These observations suggest that the mechanism by which zinc deficiency affects growth and metabolism may be via inhibition of prostaglandin synthesis from essential fatty acids. This hypothesis was examined using zinc deficient rats supplemented with oils containing various concentrations of essential fatty acids. Male Wistar rats were maintained on a zinc deficient diet for 5 weeks and supplemented daily with one of three oils containing different concentrations of essential fatty acids: olive oil (mainly oleic acid), safflower oil (mainly linoleic acid), or evening primrose oil (mainly linoleic and γ-linolenic acids). The olive oil treated rats did not benefit from this treatment in any respect. Dermal lesions were actually worse in this group than in the untreated zinc deficient rats. Safflower oil supplementation significantly inhibited the development of dermal lesions but was of only marginal benefit with respect to growth. Evening primrose oil supplementation also blocked the development of dermal lesions and restored growth to 50% of control. It is suggested that a primary defect of zinc deficiency is to inhibit essential fatty acid metabolism to prostaglandins either by blocking linoleic acid desaturation to γ-linolenic acid or by inhibiting mobilization of dihomo-γ-linolenic acid from tissue membrane stores.

N-6 fatty acid metabolism was compared in NIH-3T3 cells and DT cells, which differ only in the presence of the v-Ki-ras oncogene. Non-dividing cells were incubated with [1-14C]-labelled fatty acids (18:2n-6, 18:3n-6, 20:3n-6 and 20:4n-6) at different time intervals (2–24 h) and concentration (0–120 µM). In both cells lines, the uptake of different fatty acids from the medium was similar and reached a maximum at 6–8 h. All fatty acids reached the same maximum level in DT cells, whereas, the relative uptake of added fatty acids by NIH-3T3 cells was different: 20:4n-6>20:2n-6>18:2n-6=18:3n-6. Throughout the incubation (2–24 h), desaturation and elongation of n-6 fatty acids was more active in DT cells than in NIH-3T3 cells. However, in both cell lines, incubated with different n-6 fatty acid precursors, the levels of radiolabelled 20:4n-6 were relatively constant. In DT cells, phosphatidylcholine was found to be the major fraction labelled with n-6 fatty acids precursors and those of endogenous synthesis, whereas, in NIH-3T3 cells the neutral lipid fraction, particularly triglycerides, was also strongly labelled. In concentration dependent studies, phospholipid labelling by fatty acids was saturable. At lower concentrations, especially in DT cells, phospholipids were labelled predominantly. As the concentration increased there was an overflow into the triglyceride fraction. Since the differences in fatty acid metabolism between the two cell lines cannot be related to the growth rate, it is suggested that they were a consequence of the expression of the v-Ki-ras oncogene.

We have studied the effects of Efamol evening primrose oil (EPO) on fatty acid-binding proteins (L-FABP) of rat liver. EPO contains 72% cis-linoleic acid and 9% cis-gamma linolenic acid. EPO has been clinically used for treatment of a number of diseases in humans and animals. EPO is also known to lower cholesterol level in humans and animals. Feeding of an EPO supplemented diet to rats (n = 9) for 2 months decreases the oleate binding capacity of purified L-FABP of rat liver whereas the palmitate binding activity was increased by 38%. However, EPO feeding did not alter the L-FABP concentrations significantly as measured by using the fluorescence fatty acid probe, dansylamino undecanoic acid. Endogenous fatty acid analysis of L-FABPs revealed significant qualititative and quantitative changes in fatty acid pattern after EPO feeding. EPO feeding decreased the endogenous palmitate level by 53% and oleate level by 64% in L-FABPs and also EPO feeding decreased the total endogenous fatty acid content from 62 nanomole per mg of protein to 42 nanomole per mg of L-FABP (n = 3).

1. The effects of essential fatty acids (γ-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid), at a dose of 4.8 g/day, given in combination as dietary supplements, on cytokine production were investigated in patients with colorectal cancer. 2. Total serum cytokines - interleukin (interleukin-1β, 2, 4 and 6), tumour necrosis factor-α and interferon-γ - were analysed using the enzyme-linked immunosorbent assay technique at different time intervals during the course of essential fatty acid supplementation. 3. Fatty acid uptake and patient compliance were confirmed by a significant increase in serum levels of γ-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid in all three fractions: triacylglycerol, cholesterol and phospholipid. 4. There was no significant alteration in total serum cytokine concentration/levels in the first 2 months of essential fatty acid ingestion, but the levels of serum cytokines steadily declined thereafter, reaching minimum levels after 6 months of essential fatty acid supplementation. 5. Essential fatty acids, at the dose and duration (6 months) used in this study, reduced total serum interleukin-1β levels by 61% (P = 0.044), interleukin-2 by 63% (P = 0.05), interleukin-4 by 69% (P = 0.025), interleukin-6 by 83% (P = 0.030), tumour necrosis factor-α by 73% (P = 0.040) and interferon-γ by 67% (P = 0.050). 6. Three months after cessation of essential fatty acid intake, however, these cytokine levels returned to presupplementation values. 7. This present study has shown that long-term n-3 and n-6 EFA ingestion results in a significant reduction in circulating key cytokines. The precise mechanism of this reduction is unclear.

The effect of dietary fats on essential fatty acid metabolism in rats subjected to chemically induced hepatocarcinogenesis was studied. Sixty male rats were fed a diet supplemented with one of the following three oil compositions: 10% hydrogenated coconut oil (HCO); 5% hydrogenated coconut oil and 5% γ-linolenic acid (18:3n-6)-rich evening primrose oil (EPO); or 5% hydrogenated coconut oil and 5% marine oil (FO). Half of the animals in each dietary regimen were subjected to hepatocarcinogenesis induction using diethylnitrosamine and 2-acetylaminofluorene (2-AAF) followed by partial hepatectomy, whereas the other half underwent hepatectomy without receiving diethylnitrosamine and 2-acetylaminofluorene. Liver phospholipid composition was analyzed. In comparison to the HCO group, the EPO group showed raised levels of arachidonic acid (20:4n-6) and suppressed n-3 fatty acids. The FOgroup, on the other hand, showed suppressed levels of n-6 and increased n-3 fatty acids. Hepatocarcinogenesis suppressed the level of 20:4n-6 and this effect was greater in the FO rats. The levels of dihomo-γ-linolenic acid (20:3n-6) were increased by the hepatocarcinogenic treatment, and this effect was further accentuated in the EPO rats. These results suggest that hepatocarcinogenesis may suppress the activity of Δ-5-desaturase, which may be one of the reasons why tumor cell membranes have low levels of long chain fatty acids, especially 20:4n-6 cells, and have an impaired capacity to undergo lipid peroxidation.

This study addressed the possibility that zinc deficiency has different effects on the fatty acid composition of triglyceride compared to total phospholipid. Male weanling Sprague-Dawley rats were maintained for 6 weeks on a semisynthetic diet deficient in zinc (3 mg/kg zinc). Control rats (40 mg/kg zinc) were pair-fed. Lipid fractionation and fatty acid analysis were by thin-layer and gas chromatography, respectively. In zinc-deficient rats, the percentage of linoleic acid was increased or that of arachidonic acid was decreased in total phospholipids of plasma, liver, and testis, and in skin total lipids. Saturated and monounsaturated fatty acids were increased in the triglyceride of liver but decreased in the triglyceride of epididymal fat of zinc deficient rats. Essential fatty acids, as a proportion of total fatty acids, were decreased in triglyceride of liver but increased in triglyceride of epididymal fat of zinc-deficient rats. Our fatty acid data from tissue total phospholipids therefore support the concept that linoleic acid desaturation is impaired in zinc deficiency.

Guinea pigs were fed regular chow diets supplemented with 5% (by weight) safflower oil, evening primrose oil, or linseed oil for 6 weeks. The unsaturated fatty acid content of these oils was 78.9% of 18:2n6, 74.1% of 18:2n6, and 9.2% of 18:3n6, or 21.5% of 18:2n6 and 46.9% of 18:3n3, respectively. In comparison with 18:2n6, dietary supplementation with 18:3n6 significantly increased the tissue levels of 18:3n6 and 20:3n6, whereas dietary 18:3n3 significantly elevated the levels of 18:3n3 in plasma and liver lipids. Dietary 18:3n3 also significantly increased 22:5n3 and 22:6n3 in total phospholipids. The tissue levels of 20:4n6, on the other hand, were not affected by either treatment. These data suggest that both δ6- and δ5desaturation of n-6 fatty acids in guinea pigs are low, and that the metabolism of n-3 and n-6 fatty acids may be regulated by two different enzyme systems.

Weanling male rats were fed semipurified diets containing 20% protein derived from casein, soy protein, or wheat gluten for 5 weeks. The fat source was 2% safflower oil (containing 79.4% 18:2n−6). In comparison with the casein-fed rats, the growth rate of rats fed plant proteins was slower, particularly that of rats fed the wheat gluten diet. The plasma cholesterol levels were significantly lower in rats fed wheat gluten than in those fed the other dietary protein regimens. The fatty acid compositions of plasma and liver lipids were also examined. The ratios of 16:1/16:0, 18:1/18:0 and 20:4n–6/18:2n–6 in both plasma and liver phospholipids and cholesteryl esters were consistently reduced in animals fed plant protein suggesting a reduced activity of fatty acid desaturation. The reduction of fatty acid desaturation may possibly be attributed to the low lysine/arginine ratio in plant proteins.

Untreated streptozotocin-diabetic (7 weeks duration) rats showed reductions (all p< 0.01; percentages in brackets) in motor and sensory nerve conduction velocity (MNCV; 14 %, SNCV; 17 %) and in sciatic nerve contents of nerve growth factor (NGF; 57 %), substance P (SP; 53 %) and neuropeptide Y (NPY; 39 %). Treatment with a γ-linolenic acid-α-lipoic acid conjugate (GLA-LA; 35 mg · day–1· rat–1) attenuated (p< 0.05) these reductions to MNCV (8 %), SNCV (5 %), NGF (19 %), SP (23 %), NPY (20 %), such that the values in GLA-LA-treated diabetic rats did not differ significantly from those of control non-diabetic animals. Treatment with alpha-lipoic acid alone at 100 mg/kg i. p. was without effect on these variables except for NGF (33 % reduction, p< 0.05) and treatment with the antioxidant, butylated hydroxytoluene (1.5 % dietary supplement) did not affect any deficits. These data show that GLA-LA is effective in improving both electrophysiological and neurochemical correlates of experimental diabetic neuropathy. [Diabetologia (1998) 41: 839–843]Untreated streptozotocin-diabetic (7 weeks duration) rats showed reductions (all p< 0.01; percentages in brackets) in motor and sensory nerve conduction velocity (MNCV; 14 %, SNCV; 17 %) and in sciatic nerve contents of nerve growth factor (NGF; 57 %), substance P (SP; 53 %) and neuropeptide Y (NPY; 39 %). Treatment with a γ-linolenic acid-α-lipoic acid conjugate (GLA-LA; 35 mg · day–1· rat–1) attenuated (p< 0.05) these reductions to MNCV (8 %), SNCV (5 %), NGF (19 %), SP (23 %), NPY (20 %), such that the values in GLA-LA-treated diabetic rats did not differ significantly from those of control non-diabetic animals. Treatment with alpha-lipoic acid alone at 100 mg/kg i. p. was without effect on these variables except for NGF (33 % reduction, p< 0.05) and treatment with the antioxidant, butylated hydroxytoluene (1.5 % dietary supplement) did not affect any deficits. These data show that GLA-LA is effective in improving both electrophysiological and neurochemical correlates of experimental diabetic neuropathy. [Diabetologia (1998) 41: 839–843]

In a dietary supplementation study of 30 subjects with early Alzheimer's disease [1], 15 received evening primrose oil plus zinc sulphate plus sodium selenite and 15 received olive oil. We have now looked at the effects of the supplements on the lipid abnormalities noted in the patients. The proportion of saturated fatty acids in plasma phospholi-pids was reduced after supplementation while the more unsaturated red cell (RBC) membrane phospholipids showed no change, i.e. the relative unsaturation of the red cell phospholipids was not altered by the dietary supplementation that significantly reduced the saturation of the plasma phospholipids. There may thus be a defect of fatty acid incorporation into the red cell membrane phospholipids or an unidentified abnormality of the structure which leads to the altered fatty acid constitution without altered fluidity, as other studies have found no change in the fluidity of the RBC membranes in Alzheimer's disease. Impaired uptake of cholesterol by the erythrocyte is the hypothesis favoured and the possible effects of impaired uptake of cholesterol by the brain are considered. Reduced cholesterol accumulation may coexist with increased lipid peroxi-dation and study of the relationship of the two processes may be valuable. Although the dietary supplements were designed to be antioxidant, their benefit may have derived from delivery of lipids to tissues, and strategies for increasing the delivery of cholesterol to the brain should be identified.

Elevated oxidative stress and impaired n-6 essential fatty acid metabolism contribute to defective nerve conduction velocity (NCV) and perfusion in diabetic rats, which may be corrected by free radical scavenger and γ-linolenic acid (GLA) treatments. α-Lipoic acid (LPA) has antioxidant actions and both LPA racemate (racLPA) and GLA treatments produced benefits in clinical neuropathy trials. The aims were to study LPA action on neurovascular function in diabetic rats and to investigate potential interactions for co-treatment with GLA and other essential fatty acids. After 6 weeks of diabetes, 2 weeks of racLPA treatment corrected 20 % sciatic motor and 14 % saphenous sensory NCV deficits. The ED50for motor NCV restoration was approximately 38 mg kg–1day–1. racLPA also corrected a 49 % diabetic deficit in sciatic endoneurial blood flow. R and S-LPA enantiomers were equipotent in correcting NCV and blood flow deficits. Treatment of diabetic rats with low doses (20 mg kg–1day–1) of racLPA and GLA, while having modest effects on their own, showed evidence of marked synergistic action in joint treatment, completely correcting motor NCV and blood flow deficits. This was also noted for the novel compound, SOC0150, which contains equimolar proportions of LPA and GLA (ED509.3 mg kg–1day–1, containing 3.5 mg LPA). NCV effects also showed marked synergism when racLPA:GLA ratios were varied over a 1:3–3:1 range. In contrast, a compound containing LPA and the n-3 component, docosahexaenoic acid, showed similar activity to LPA alone. Thus, LPA-GLA interactions yield drug combinations and compounds with an order of magnitude increase in efficacy against experimental diabetic neuropathy and are worthy of consideration for clinical trials. [Diabetologia (1998) 41: 390–399]Elevated oxidative stress and impaired n-6 essential fatty acid metabolism contribute to defective nerve conduction velocity (NCV) and perfusion in diabetic rats, which may be corrected by free radical scavenger and γ-linolenic acid (GLA) treatments. α-Lipoic acid (LPA) has antioxidant actions and both LPA racemate (racLPA) and GLA treatments produced benefits in clinical neuropathy trials. The aims were to study LPA action on neurovascular function in diabetic rats and to investigate potential interactions for co-treatment with GLA and other essential fatty acids. After 6 weeks of diabetes, 2 weeks of racLPA treatment corrected 20 % sciatic motor and 14 % saphenous sensory NCV deficits. The ED50for motor NCV restoration was approximately 38 mg kg–1day–1. racLPA also corrected a 49 % diabetic deficit in sciatic endoneurial blood flow. R and S-LPA enantiomers were equipotent in correcting NCV and blood flow deficits. Treatment of diabetic rats with low doses (20 mg kg–1day–1) of racLPA and GLA, while having modest effects on their own, showed evidence of marked synergistic action in joint treatment, completely correcting motor NCV and blood flow deficits. This was also noted for the novel compound, SOC0150, which contains equimolar proportions of LPA and GLA (ED509.3 mg kg–1day–1, containing 3.5 mg LPA). NCV effects also showed marked synergism when racLPA:GLA ratios were varied over a 1:3–3:1 range. In contrast, a compound containing LPA and the n-3 component, docosahexaenoic acid, showed similar activity to LPA alone. Thus, LPA-GLA interactions yield drug combinations and compounds with an order of magnitude increase in efficacy against experimental diabetic neuropathy and are worthy of consideration for clinical trials. [Diabetologia (1998) 41: 390–399]

To test the effect of prostaglandin A2(PGA2) on renal function, infusions of PGA2(0·7 ng/ kg/min), arginine-vasopressin (AVP) (1·25 ng/kg/min) and PGA2plus AVP were administered to male rats made resistant to the antidiuretic effect of AVP by pre-treatment with lithium. In non-lithium-treated control rats, AVP had its expected antidiuretic action but in lithium-treated rats neither urinary volume nor osmolarity was changed. Prostaglandin A2alone had no effect on urine output in lithium-treated rats; AVP plus PGA2infused together evoked a near normal antidiuretic response. This antidiuretic action of PGA2contrasts with the diuretic action reported by others. However, our infusion rates were 300–4000 times lower than those of other workers and it is suggested that PGs may have opposite actions on the kidney depending on their concentration.The effect of indomethacin (a blocker of prostaglandin synthesis) on urine flow was tested in five groups of rats on different régimes of liquid intake. Urine flow was reduced in the three groups with the highest urine volumes before treatment, and increased in the two groups with the lowest urinary volumes, again indicating that PGs may have both diuretic and antidiuretic actions.

We have reviewed the evidence for changes in lipids in blood and brain in ageing animals, in ageing humans and in humans with Alzheimer's disease. Studies of anti-oxidant enzymes in isolation are unsatisfactory and other markers of the oxidation/reduction status of tissues are required. There is less work showing increased protein oxidation with ageing but so far it seems to be more consistent. Possible associations of free radical activity with amyloid deposition in Alzheimer's disease are discussed.

1. In the perfused rat mesenteric vascular bed, the effects of angiotensin II, cortisol and prostaglandin E2 on the vascular responses to noradrenaline or potassium chloride were studied. 2. Angiotensin II in subpressor concentrations potentiated the vasoconstrictor response to noradrenaline and potassium chloride. This effect of angiotensin II was inhibited in the presence of indomethacin and prostaglandin E2. 3. Cortisol in physiological concentrations inhibited the potentiating effect of angiotensin II. 4. Prostaglandin E2 enhanced the vasoconstrictor response to noradrenaline. This effect was not abolished by cortisol. 5. These results suggest that some actions of angiotensin II and cortisol in vivo are mediated by the regulation of prostaglandin synthesis or release.

Lipid metabolism has been considered recently as a novel target for cancer therapy. In this field, lithium gamma-linolenate (LiGLA) is a promising experimental compound for use in the treatment of human tumours. In vivo and in vitro studies allowed us to assess the metabolism of radiolabelled LiGLA by tumour tissue and different organs of the host. In vitro studies demonstrated that human pancreatic (AsPC-1), prostatic (PC-3) and mammary carcinoma (ZR-75-1) cells were capable of elongating GLA from LiGLA to dihomo-gamma-linolenic acid (DGLA) and further desaturating it to arachidonic acid (AA). AsPC-1 cells showed the lowest delta5-desaturase activity on DGLA. In the in vivo studies, nude mice bearing the human carcinomas were given Li[1-(14)C]GLA (2.5 mg kg(-1)) by intravenous injection for 30 min. Mice were either sacrificed after infusion or left for up to 96 h recovery before sacrifice. In general, the organs showed a maximum uptake of radioactivity 30 min after the infusion started (t = 0). Thereafter, in major organs the percentage of injected radioactivity per g of tissue declined below 1% 96 h after infusion. In kidney, brain, testes/ovaries and all three tumour tissues, labelling remained constant throughout the experiment. The ratio of radioactivity in liver to tumour tissues ranged between 16- and 24-fold at t = 0 and between 3.1- and 3.7-fold at 96 h. All tissues showed a progressive increase in the proportion of radioactivity associated with AA with a concomitant decrease in radiolabelled GLA as the time after infusion increased. DGLA declined rapidly in liver and plasma, but at a much slower rate in brain and malignant tissue. Seventy-two hours after the infusion, GLA was only detected in plasma and tumour tissue. The sum of GLA + DGLA varied among tumour tissues, but it remained 2-4 times higher than in liver and plasma. In brain, DGLA is the major contributor to the sum of these fatty acids. Data showed that cytotoxic GLA and DGLA, the latter provided either by the host or by endogenous synthesis, remained in human tumours for at least 4 days.

Effects of supplementation of saturated fatty acids (16:0 and 18:0) on metabolism of the cytotoxic n-6 fatty acids in cultured human monocyte-like cells (U937) have been examined. U937 cells were incubated in 5% delipidated fetal bovine serum containing 16:0 and 18:0. Supplementation of either 16:0 or 18:0 has no significant effect on the uptake of 18:2n-6 and 18:3n-6. However, addition of 16:0 to the medium increased whereas 18:0 suppressed the cytotoxic effects of 18:2n-6 and 18:3n-6. In addition, 16:0 supplementation reduced the incorporation of n-6 fatty acids in cellular phospholipid fraction, and enhanced the metabolism of n-6 fatty acids, particularly the conversion of 20:3n-6 to 20: 4n-6 in U937 cells. Results with microsomes prepared from U937 cells also showed that 16:0 supplementation increased the ?5 desaturase activity. This may be related in part to an increase in the availability of 20:3n-6, since results obtained in a separate study have shown that 16:0 competed with 20:3n-6 for incorporaton into the phospholipid molecule at sn-2 position. Increasing the availability and formation of long chain n-6 fatty acids, which are cytotoxic, might also be responsible for increasing cytotoxicity of 16:0 supplementation.

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 ?9 desaturase by 50%. Feeding the HCO diet to mice previously fed the EPA/GLA diet led to a progressive increase in ?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 ?9 desaturase without altering the microsome physicochemical parameters.

The present study examined the effects of supplementation of either 18:3n-3 or a mixture of its post-Δ6-desaturation metabolites, 20:5n-3/22:6n-3, in combination with either 18:2n-6 or its immediate Δ6-desaturation product, 18:3n-6, in the maternal diet (n-3 to n-6 ratio at 0.25) on brain, liver, heart, and kidney glycerophospholipid fatty acid composition in dams (B6D2F1mice) and their 12-day-old suckling pups. As expected, n-3 and n-6 fatty acids competed for incorporation into tissue glycerophospho-lipids in both dams and their suckling pups. Feeding a 20:5n-3/22:6n-3 as compared with an 18:3n-3 rich diet increased the tissue levels of 20:5n-3 and 22:5n-3, whereas it decreased those of 20:3n-6 and 20:4n-6. Replacing 18:2n-6 with 18:3n-6 in the maternal diet increased significantly the levels of 18:3n-6, 20:3n-6, and 20:4n-6, whereas it reduced those of 20:5n-3. However, the effects of maternal dietary fats on tissue fatty acid compositions in pups were qualitatively similar to but quantitatively smaller than those in dams. The discrepancy might be due to differences in the composition of fatty acids taken up and synthesized by the dams and that transferred to the pups.

Weanling female rats raised on a fat-free diet for 8 weeks were then given the same diet supplemented with 0, 0.25, 0.5, or 1% by weight of cholesterol in addition to 10% of safflower oil for 3 days. Fatty acid compositions of cholesteryl esters (CE), triglycerides (TG), and phospholipids (PL) in liver and plasma were examined. Cholesterol feeding increased plasma and liver cholesterol contents and also affected the patterns of n-6 polyunsaturated fatty acids. There were no consistent changes in either plasma and liver TG which contained little 20:3n-6 and 20:4n-6. The levels of 20:3n-6 increased in plasma and liver PL, while proportions of 20:4n-6 decreased in liver and plasma CE. However, the absolute amount of 20:4n-6 in cholesteryl esters increased because of a threefold rise in cholesteryl ester levels. The changes might be attributable to an increased utilization of 20:4n-6 for cholesterol transport and/or an inhibition of δ5-desaturation of n-6 fatty acids by cholesterol feeding.

There is evidence of a close interrelationship between essential fatty acid (EFA) metabolism and the ability to respond to viral infections. EFAs are required to enable interferon to exert its antiviral effects. Viral infections both in vivo and in vitro induce abnormalities of EFA metabolism. Patients with atopic eczema who are highly susceptible to viral infections have reduced levels of 6-desaturated EFAs. In a placebo-controlled study in post-viral fatigue syndrome EFA supplementation with n-3 and n-6 EFAs has been found effective in reversing the plasma EFA abnormalities and treating the clinical state. These observations suggest that normal EFA metabolism is of major importance in regulating the response to viral infections.

The effects of aldosterone on sodium, potassium and water excretion during various treatment regimes were studied in six Merino ewes. Urine was collected from 12.00 to 14.00 h and from 14.00 to 16.00 h each day. Intravenous injections of either 1 ml isotonic saline or 500 μg aldosterone were given at 13.30 h and excretion during the second collection period compared with that in the first. When each animal was given a salt (NaCl) supplement of 80 mequiv./day by i.v. injection, aldosterone caused marked sodium retention with no effect on potassium. When salt supplements of 400 mequiv./day were given, aldosterone lost its sodium-retaining action in all animals and caused a marked saluresis with a small increase in potassium excretion in five sheep out of six. Injections of sheep pituitary prolactin or of oxytocin restored the sodium-retaining action of aldosterone in spite of a continued high salt intake. The animals gained very little weight when treated with 400 mequiv. salt alone but did gain significantly when treated with salt plus prolactin. The weight gain was rapidly lost when the prolactin and high salt intake were discontinued.

Thirty-nine decerebrate rabbits, curarized and maintained by artificial ventilation, were used in the experiments. In a control group which received only saline intravenous infusions, arterial pressure remained virtually unchanged for 6 h after decerebration. Three other groups were used, all of which received intravenous infusions of aldosterone starting 1 h after decerebration and continuing for 5 h: in these groups the pressure 1 h after decerebration was taken as 100%. In a group of animals which received a normal diet before the acute experiment, the mean percentage pressure rise at the end of 5 h of aldosterone infusion was 20·0 ± 2·3 (s.e.m.)%. In a group whose drinking water had been replaced with 1% NaCl solution, the mean percentage pressure rise after 5 h was 29·6 ± 3·2. In a group pretreated with a low salt intake, the mean percentage pressure rise after 5 h was 10·3 ± 2·8%. These results show that intravenous infusions of aldosterone at the rate of 6 μg/kg/h can raise arterial pressure in acute experiments, and that varying the sodium intake can alter the responsiveness of the cardiovascular system to the hypertensive action of aldosterone.

VERY little is known about the endocrine regulation of amniotic fluid volume and composition1,2. Vizsolyi and Perks2have described a technique for studying the transfer of fluid across the amniotic membrane of the guinea pig in vitro. They showed that arginine vasotocin and arginine vasopressin (antidiuretic hormone, ADH) could stimulate the movement of fluid from the maternal to the foetal side of the membrane. Because prolactin is found in remarkably high concentrations (up to 10 µg ml−1) in primate amniotic fluid3,4and affects renal function5–8, we have investigated the effect of prolactin as well as of arginine vasopressin on the guinea pig amniotic membrane. Because cortisol can reverse the usual antidiuretic effect of ADH and because prolactin can restore this effect9, we have also investigated the action of cortisol. We have shown that ADH and prolactin have opposite effects on the amniotic membrane and that, in both cases, their actions can be reversed by cortisol. We suggest that fluid transfer across the amniotic membrane may provide an insight to the functioning of the kidneys, the ciliary body and the choroid plexus.

Infusion into the rat mesen-teric artery of tonin, an enzyme which forms angiotensin II directly from a natural protein plus the tetradecapeptide renin substrate, significantly potentiated the vasoconstrictor response to norepineph-rine. This effect was not inhibited by the simultaneous administration of an inhibitor of angiotensin I-converting enzyme or by Sar1Ala8angiotensin II. These substances block the pressor effect of the angi-otensins I and II, respectively.The authors wish to thank Mrs. V. Lacombe for secretarial work.The synthetic saralasin, antagonist of angiotensin II (P 113), was kindly supplied by Eaton Laboratories, Nowrich, New York.

To examine the relationship between plasma lipoproteins and apolipoproteins in men with convictions for violent offences, blood was obtained from 15 men with a history of violence who were serving prison sentences for violent offences, and 25 age-matched male controls from the staff of the Argyll and Bute Psychiatric Hospital, who had no criminal records. The two groups did not differ in plasma total cholesterol concentrations, HDL-C, LDL-C, VLDL-C or in HDL subfractions. The most significant differences in the offenders were higher apoprotein AIV (3.62 vs0.85: p= 0.000001) and higher apoprotein E (7.70 vs5.19: p= < 0.0002).