I. Monosodium glutamate (MSG) was administered by various methods to mice and rats of various ages and the incidence of obesity was later measured.2. Newborn mice were injected subcutaneously with 3 mg MSG/g body-weight at I, 2 , 3, 6, 7 and 8 d of age: 16% died before weaning. Of the survivors, 90% or more became markedly obese. Mean carcass lipid content was increased by about I Z O~~ in both sexes at 2-30 weeks of age. In male mice, MSG treatment increased body-weight and epididymal fat pad weight, and greatly decreased adrenaline-stimulated lipolysis in isolated fat cells. Body-weight of females was not increased significantly. Food intake was not increased in either sex from weeks 13 to 15. Blood glucose level was not generally increased by MSG but some of the male mice had abnormally high values.3. Obesity was not detected in the offspring of female mice that had received IOO g MSG/kg diet, either from 3 weeks before mating until weaning, or from the 14th day of pregnancy until weaning.4. Intraperitoneal injection of 10 mg MSG/g body-weight (in two doses) at weaning increased carcass lipid content in female mice by 34% by 23 weeks of age, but female rats were not affected.5. The addition of zo g MSG/I to the drinking-water from weaning onwards did not increase carcass lipid content in female rats or mice.6. The addition of 20 g MSG/kg diet from weaning onwards did not alter body-weight or carcass lipid content in male and female rats by 14 weeks of age.7. The obesity induced in mice by MSG was not associated with hyperphagia, unlike genetic obesity and obesity induced by gold thioglucose (GTG).8. All types of mouse studied, obese and lean, had essentially the same linear relationship between carcass water content and carcass lipid content.9. Although MSG-obese mice could not readily be differentiated from normal mice by the increase in body-weight, which was only about 10% compared to 50-120% for genetic and GTG-induced obesity, the proposed schedule of injections in the newborn was almost I O O~~ reliable in inducing a high extent of adiposity.

Abstract(S)-( + )-Ibuprofen, a-methyl-4-(2-methylpropyl)-benzeneacetic acid, crystallizes with two molecules in the asymmetric unit to form a cyclic hydrogenbonded dimer. Within the dimer each molecule shows subtle conformational differences via rotations

I. A critical analysis of the biological antioxidant theory of vitamin E function has been made and the implications of the theory have been tested.2. When small amounts of [5-Me-'*C]a-tocopherol were present in lipid systems subject to autoxidation in vitro, it was found that, whether the tocopherol was the sole antioxidant or was in synergistic combination with a secondary antioxidant (ascorbic acid), peroxidation did not occur without concomitant destruction of the tocopherol. This was so, whether a simple fat substrate or a liver homogenate (subject to catalysis) was used. The decomposition of tocopherol took place even when the secondary antioxidant was in large excess, as would occur under physiological conditions in the vitamin E-deficient animal, and accelerated as the induction period neared its end.3. When [5-Me-14C,3H]a-tocopherol and ascorbic acid were used as a synergistic antioxidant couple in vitro, tocopherol recovered from the peroxidizing system always had the same isotopic ratio as the starting material. This means that regeneration of tocopherol by the secondary antioxidant cannot involve, as an intermediate, a tocopherol carbon radical formed by loss of hydrogen from the 5-methyl group. Such radicals probably dimerize before they can be regenerated. The same result was found when doubly labelled a-tocopherol was given to the rat and recovered later from its tissues. 4.In a series of experiments, rats were rigorously depleted of vitamin E for periods up to 7 months and then given as little as 50 pg [14C]n-a-tocopherol. They were then given, either by stomach tube daily or by dietary addition, large amounts of methyl linoleate or vitamin Efree polyunsaturated fatty acid methyl esters prepared from cod-liver oil and compared with controls given methyl oleate for up to 3 I days. When the possibility of interaction between the lipid and tocopherol in the gut was eliminated, analyses of liver, kidney, testis, adrenal, adipose tissue, whole carcass and faeces showed that there was no effect of the polyunsaturated fatty acids on either the metabolism or recovery of ['4C]or-tocopherol in any of the animals.5. When interaction between the administered fatty acid esters and tocopherol in the gut was allowed to take place, a marked destruction of [14C]a-tocopherol in the tissues was observed in animals given the polyunsaturated esters. The importance of oxidative destruction of tocopherol in the gut before absorption was demonstrated in a nutritional trial, in which codliver oil and lard were compared and the degrees of resistance of rats' erythrocytes to dialuric acid-induced haemolysis was used as an index of vitamin E depletion.6. Similar experiments with [14C]cr-tocopherol in weanling rats given large amounts of codliver oil methyl esters also showed little effect. Although there was a suggestion that prolonged feeding of partly peroxidized polyunsaturated esters could lead to a slight depression of tissue tocopherol concentrations, no significant differences were usually obtained.7. Fourteen-day-ol...

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I . A micro-adaptation of the iodimetric method has been used to determine lipid peroxides in the tissues of vitamin E-deficient rats and chicks.2. No increases in lipid peroxide were found in liver, kidney or adipose tissue of rats with nutritional liver necrosis due to deficiency of vitamin E and selenium. When liver necrosis was induced by giving rats a casein diet and silver acetate solution to drink, the peroxide value of the adipose tissue was not increased.3. Degeneration of the testes of vitamin E-deficient rats was not accompanied by a rise in the peroxide value of the tissue lipids.4. There was an increase in cathepsin activity of the kidneys of rats displaying the phenomenon of renal autolysis (post mortem), but there was no increase in lipid peroxide content. 5.No rise in lipid peroxide was found in dystrophic chick breast muscle, in cerebellum, brain and adipose tissue of chicks with encephalomalacia nor in the liver of chicks with exudative diathesis.6. In rat liver, kidney, testis and leg muscle, peroxide values in the range 1-40 p-equiv./g lipid were found, and these values were not altered either by a substantial change in the degree of unsaturation of the dietary lipid or by the addition of vitamin E to the diet. Dietary addition of N,N'-diphenyl-p-phenylenediamine (DPPD) or 6-ethoxy-1,z-dihydro-2,2,4-trimethylquinoline (ethoxyquin) also failed to affect the peroxide value of liver. The possibility that lipid peroxide is a normal metabolite of these tissues is discussed.7. Peroxide values of rat adipose tissue were never found to be greater than 40 p-equiv./g lipid and were readily decreased by the addition of vitamin E to the diet or by a decrease in the unsaturation of the dietary lipid. The peroxide content of this tissue may depend upon the uptake of peroxidized dietary lipid.8. The conclusion from this study of true lipid peroxides in animal tissues is that the biological role of vitamin E is not connected with lipid peroxidation in vivo, in agreement with our previous studies on the metabolism of the fatty acid substrates of peroxidation and of a-tocopherol and other postulated biological antioxidants.The hypothesis that vitamin E functions solely as a physiological antioxidant has been critically examined by . I n that study and in two succeeding ones we found that the metabolism of [14C]a-tocopherol was unaffected by large amounts of unsaturated lipid in the diet or by the imposition of other stresses on the vitamin E status of the animals and concluded that lipid peroxidation was not causally concerned in the aetiology of vitamin E deficiency disease. Furthermore, in a recent study we could find no evidence that the peroxidative loss of polyunsaturated fatty acids (PUFA) was a general feature of vitamin E deficiency, although a significant role for vitamin E in the interconversion of highly unsaturated fatty acids was not denied.Although, therefore, most of the evidence for the biological antioxidant hypothesis seems to be circumstantial, there is nevertheless some apparently direct ...