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1. The effect of cobalamin inactivation by the anaesthetic gas nitrous oxide on the concentration of S-adenosylmethionine (Ado Met) in brain and liver of fruit bats (Rousettus aegyptiacus) was examined.2. Test animals exposed to N2O–oxygen (50:50, v/v) developed ataxia and paralysis leading to death after an average of 9·8 weeks (n 6). Animals receiving pteroylmonoglutamic acid supplements in the diet became ataxic earlier (mean 8·8 weeks) while those receiving methionine supplements survived for significantly longer periods (12·5 weeks, P < 0·01).3. Plasma cobalamin levels indicated severe depletion of cobalamin stores in N2O-exposed animals.4. The mean concentration of Ado Met in the brain of N2O-treated bats was nearly 50% higher than that of untreated controls. Ado Met levels in treated bats receiving pteroylmonoglutamic acid or methionine supplements were respectively 18 and 25% higher than in controls. In contrast, the concentration of Ado Met in the liver of all the N2O-treated groups was slightly lower than in controls.5. These results suggest that the N2O-induced neuropathy in the fruit bat is not related to a depletion of Ado Met in the nervous system.

Fruit bats are an animal model for the neurologic damage which occurs in vitamin B12-deficient humans. Cobalamin (vitamin B12) analogs were not detected in the plasma of fruit bats treated with nitrous oxide (N2O), which inactivates cobalamin. This observation does not lend support to the suggestion that the neurological changes associated with cobalamin inactivation by N2O and/or cobalamin deficiency per se may be related to the accumulation of cobalamin analogs. However, although the plasma of control fruit bats lacked analogs, we did find analogs in their livers, at levels about 10% of total liver corrinoids, similar to human liver analog levels.

Spinal cords were removed from ten Egyptian fruit bats Rousettus aegyptiacus and the lipids analysed. The major phosphatides were choline glycerophosphatide (32.3%), ethanolamine glycerophosphatide (29.3%), serine glycerophosphatide (15.2%) and phosphatidylinositol (8.4%). Sphingomyelin accounted for 13.8% of the phospholipid. Glycosphingolipids amounted to 43.2 mol/100 mol lipid phosphorus, plasmalogens 32.5 mol/100 mol P and cholesterol 159.5 mol/100 mol P. The fatty acid composition of whole cord, sphingomyelin and non-hydroxy cerebroside were determined. The results were compared with data from other species.

Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment - the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

[2-14C]Tetrahydropteroylglutamic acid and 5-[G-3H]methyltetrahydropteroylglutamic acid were given intraperitoneally to fruit bats. Folate polyglutamates were formed in the liver from both substrates in different amounts and at different rates. The methylfolate pool appeared to remain separate from the tetrahydrofolate pool. More polyglutamate was formed from tetrahydropteroylglutamic acid than from 5-methyltetrahydropteroylglutamic acid. There was a fall in the folate content of the liver in the vitamin B-12-deficient bat and a more rapid incorporation of folates into polyglutamates but thereafter a more rapid loss of the labelled folate from liver.

Folate in the brain of the South African fruit bat consists of 10-formyltetrahydropteroylglutamic acid and the tri-, tetra- and penta- forms of 5-methyltetrahydropteroylglutamic acid. Following parenteral injection, only 5-[3H]-methyltetrahydropteroylglutamic acid was taken up by the brain, but none of a dose of 14C-labelled tetrahydropteroylglutamic acid was detectable. Only trace amounts of the 5-methyltetrahydropteroylglutamic acid were converted into the formyl compounds and a small amount of methyltetrahydropteroyltriglutamic acid appeared after 96 h. There was no significant difference in vitamin B-12-deficient animals.

1. 1. Fruit bats Rousettus aegyptiacus were depleted of vitamin b 12 by exposure to the gas nitrous oxide (N 2 O-oxygen, 1:1 v/v) for 57–80 days. 2. 2. Conduction velocities along the fastest fibres of the ulnar nerve, as well as the first and second peaks, were similar in control and vitamin B 12 depleted animals. 3. 3. It is concluded that neurological impairment resulting from depletion of vitamin b 12 by N 2 O does not involve significant impairment of ulnar nerve function in this species.

The weights of the brains of vitamin B12-deficient baby bats (Rousettus aegyptiacus, 4-20 day old) were slightly lower than those of B12-replete infant bats. Liver and kidney organ weights were similar in the two groups. Brain and liver B12 levels of B12-deficient baby bats were significantly lower than those of replete controls. Kidney B12 levels in deficient babies were about one quarter those of the replete babies. Brain vitamin B12 levels in B12-deficient sucklings were significantly lower than those of B12-deficient adult bats (P less than 0.01). These findings reinforce the need for adequate vitamin B12 nutrition in pregnant and lactating animals.

Recent work has shown that several folates interact with excitatory kainic acid receptors in the mammalian brain and appear to have agonist activity at these receptors. Since kainic acid is a potent neurotoxin it is possible that folates share this toxicity and that high levels of folates result in neuronal damage. Levels of methyltetrahydrofolate are markedly elevated in vitamin B12 deficiency, a disease associated with neuronal destruction. We propose that this destruction occurs as a result of a neurotoxic action of methyltetrahydrofolate. Injection of kainic acid into the basal ganglia of experimental animals produces a pattern of damage similar to that found in patients dying of Huntington's chorea. It is possible that the underlying defect in this disease resides in the pathways of folate metabolism such that a neurotoxic excess of folates accumulates in the central nervous system. Such a disease process might be arrested by antifolate drugs.

Eight healthy subjects were fed a diet containing 1–4 g eicosapentaenoic acid (EPA) daily for 8–21 days. The EPA was derived from 300–400 g per day of sardines, pilchards, herring and/or kabeljou. Sources of arachidonic acid (AA) in the diet were reduced. At the end of the experimental period there was an increase in the ratio of EPA to AA in the platelets and a decrease in platelet aggregation to ADP, epinephrine and collagen. Aggregation to AA was not reduced. Thromboxane production in response to all four agonists was reduced. Serum total and HDL cholesterol levels fell significantly but platelet counts, LDL cholesterol and triglyceride values did not change. We conclude that even a relatively modest intake of EPA derived from a mixed fish diet together with a reduction in AA intake can alter in vitro platelet function and serum lipids significantly. A long term controlled trial of a palatable mixed fish diet to assess possible antithrombotic and antiatherogenic effects is justifiable.

1. 1. Synaptosomes were prepared from the brain of cobalamin deficient and cobalamin supplemented fruit bats (Rousettus aegyptiacus) by a floatation method on a discontinuous sucrose gradient. 2. 2. There were no significant differences in fatty acid composition between the deficient and supplemented bats. 3. 3. The odd chain fatty acid 15:0 amounted to 0.2% of the total fatty acids in both groups. 4. 4. We conclude that the fatty acids of synaptosomal lipids are not a factor in the development of neural dysfunction in the cobalamin deficient fruit bat.

Myelin was isolated from the brain of adult fruit bats (Rousettus aegyptiacus) in a discontinuous sucrose gradient. Cholesterol comprised 189.0 mol/100 mol lipid phosphorus, galactolipids 60.3 mol/100 mol phosphorus and plasmalogens 32.5 mol/100 mol phosphorus. Choline and ethanolamine glycerophosphatide were present in nearly equal amounts followed by serine glycerophosphatide, sphingomyelin and inositol glycerophosphatides. The fatty acid composition of sphingomyelin and non-hydroxy cerebroside was determined by gas-liquid chromatography. Fatty acids were mainly saturated or mono-unsaturated with a small percentage of polyunsaturated fatty acids present. The lipid composition and sphingolipid fatty acid distribution in bat myelin was fairly similar to that of other species.

The rate of absorption of 14C-thiamin added to sorghum beer has been studied in isolated loops of rat duodenum and adjacent jejunum. Appreciable amounts of the vitamin were absorbed in spite of the presence in the beer of alcohol and live yeast cells avid for the vitamin. These results suggest that commercially brewed sorghum beer, a beverage consumed widely by Third World populations, can be fortified with thiamin to prevent the development of deficiency of the vitamin in habitual consumers of the beer.

1. The effect of methylcobalamin inactivation by the gas nitrous oxide on plasma amino acid and tissue methionine levels in fruit bats (Rousettus aegyptiacus) was examined.2. Animals exposed to N2O-oxygen (1:1, v/v) for 90 min daily received a fruit diet with or without methionine or betaine supplements. Exposure and diets were continued for up to 17 weeks or until neurological impairment and muscular weakness was established.3. All the groups exposed to N2O had significantly lower liver, brain and plasma methionine concentrations except the methionine-supplemented animals which showed significantly raised levels. Plasma homocysteine, which was absent in controls, was present in all the N2O-exposed groups.4. Betaine supplementation resulted in reduced accumulation of homocysteine in plasma. However, plasma and liver methionine levels were only slightly increased compared with animals on the basal diet, and brain methionine levels were the lowest of all the groups studied.5. These results support the hypothesis that reduced methionine synthesis is an important contributor to the development of neurological impairment in this species and suggest that dietary supplementation with the methionine precursor betaine cannot replace the loss of vitamin B12-dependent methionine synthesis.