1. The acute toxicity of orally administered CCl4 and its subacute toxicity (liver necrosis and hepatic fat accumulation) were studied in young adult male and female rats. CCl4 was more toxic in males than in females. The protective effects of vitamin E (D-α-tocopheryl acetate) and three synthetic antioxidants, DPPD (N,N'-diphenyl-p-phenylenediamine), ethoxyquin (6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline) and BHT (butylated hydroxytoluene) were studied.

2. Three daily oral doses (450 mg/kg) of vitamin E given before CCl4 increased survival in male rats but not consistently in females. Single oral doses (450 mg/kg) given previously at times between 24 and 72 h were also protective in males, but slightly decreased survival in females. Single intraperitoneal doses (500 mg/kg) given to female rats 1–48 h before CCl4 had no effect on survival. None of these treatments with vitamin E significantly decreased CC14-induced hepatic triglyceride accumulation. A large oral dose (2000 mg/kg) 6 h before CCl4 not only significantly increased hepatic fat accumulation but also increased mortality.

3. Three daily doses (600 mg/kg) of DPPD or a single oral dose given 72 h before CCl4 increased survival in male and female rats. When single doses of DPPD were given 6–48 h before CCl4 they had no effect on survival. In contrast, DPPD usually significantly decreased the CC14-induced hepatic triglyceride rise when given orally 6–72 h before CCl4. Single intra-peritoneal doses (100–1500 mg/kg) of DPPD, given 1–48 h before CCl4, decreased the hepatic triglyceride rise. Multiple doses of DPPD decreased CC14-induced liver necrosis, but single doses were generally less effective.

4. Three daily oral doses (300–500 mg/kg) of ethoxyquin given before CCl4 were highly effective in preventing mortality, liver necrosis and the rise in hepatic triglycerides. Single oral doses (500 mg/kg) given 72 or 48 h before CCl4 produced the same effect, but these single doses 24 or 6 h before CCl4 were without effect. The effective treatments usually increased liver weight markedly. Intraperitoneal treatment with ethoxyquin also substantially reduced the toxicity of CC14. Ethoxyquin was the most effective of all four treatments studied, and livers from animals given this substance were often nearly normal in histological appearance.

5. The activity of oral doses (400–600 mg/kg) of BHT, given 48 h or more before CCl4 was, in general, similar to that of ethoxyquin, but less marked. This substance also caused a large increase in liver weight after 48 h. Oral doses given 6–24 h before CC14 increased the CC14-induced triglyceride rise still further. Intraperitoneal doses of BHT were ineffective against acute toxicity, liver necrosis or the triglyceride rise.

6. Concentrations of a-tocopherol and the three synthetic antioxidants were measured in liver in many of the experiments. Very high hepatic concentrations of a-tocopherol could be obtained without affecting either the acute or subacute toxicity of CCl4. Ethoxyquin and BHT were rapidly eliminated from the liver after oral dosage, and when maximum concentrations were reached (24 h or less after administration) they were without protective effect. In contrast, when ethoxyquin and BHT were most active (48–96 h after administration) they could not be found in appreciable concentration in the liver.

1. A study was done on the platelet 5-hydroxytryptamine (5HT) from Africans in areas where endomyocardial fibrosis is common.

2. There were only small differences between the mean platelet or blood 5HT in Europeans and plantain-eating Africans; the distribution of the results showed a wider scatter in the African community, including values outside the upper limits of normal but not within the range reported for carcinoid.

3. Patients in hospital had lower platelet 5HT contents regardless of cardiac condition or disease than healthy Africans on similar diets, suggesting no specific abnormality related to platelet 5HT levels and endomyocardial fibrosis.

4. A small number of radioactive studies suggested that only 1–4 % of oral 5HT may reach the platelets; a significant increase in platelet 5HT did occur after a plantain meal; the in-crease after a meal but not after oral 5HT may be explained by release of endogenous 5HT from the small intestine under the influence of the high bulk of the diet. Attention is drawn to the high incidence of adult intussusception and volvulus associated with such diets.

1. An examination has been made of the plasma amino acids of adult Uganda Africans at risk to endomyocardial fibrosis compared with people from areas where the disorder is rare. The amino acid profile, both free and in the protein of the main staples, has also been examined.

2. Plasma tryptophan was found to be low in adults at risk and intermediate in Africans receiving a higher protein intake, as compared with Europeans whose protein intake might include more than 40 % as animal products.

3. Leucine and valine were also low in the plasma of adult Africans at risk.

4. The non-essential amino acids alanine and glycine were increased in the adult Africans at risk.

5. The similarity of these changes with the changes seen in kwashiorkor by other workers suggests that adherence to limited vegetable diets may introduce a chronic stress with regard to certain essential amino acids.

6. Studies on the vegetable staples used by Africans established that they are particularly poor in tryptophan and such Africans are probably dependent on other sources for their trypto-phan. None of the staples was a rich source of leucine. Plantain contained relatively large amounts of histidine, and cassava of arginine.

7. A comparative study of muscle protein suggests that the composition is similar regardless of diet and species. Leucine is quantitatively one of the most important amino acids in the muscle profile.

8.The above findings are discussed in the context of the requirements for heart muscle and the high incidence of cardiomyopathies within such African communities.

1. Rats fed on a vitamin B12-deficient or -supplemented diet were given either neomycin or a mixture of streptomycin and erythromycin by mouth for between 7 and 15 d. The urinary excretion of methylmalonic acid and the levels of vitamin B12 in plasma and tissues and of acetic and propionic acids in caecal contents were measured.

2. Both treatments caused prompt reduction of methylmalonate excretion in the deficient rats. This was apparently due to depression of the production of some precursor of methyl-malonic acid, probably propionate, rather than to an immediate effect on vitamin B12 nutrition.

3. After withdrawal of the antibiotics, neomycin-treated vitamin B12-deficient rats appeared to become partly repleted in vitamin B12, but the change in the vitamin B12 status of those which had received streptomycin and erythromycin was much smaller.

1. The changes in serum lipid and protein concentrations, and in carbohydrate tolerance were studied in eleven young male volunteers during a 3-week period of either nibbling or gorging a diet containing a high proportion of sucrose.

2. It was found that when gorging, the serum glyceride concentration rose early in the dietary period and reached a plateau, that the serum albumin concentration fell and that the glucose tolerance remained unchanged, although there was evidence for an increased rate of absorption of glucose.

3. On the nibbling regime, the serum glyceride concentration rose progressively over the 3-week period, the serum phospholipid concentration fell significantly and the serum albumin concentration fell but to a lesser degree than when gorging.

4. The glucose tolerance was improved when nibbling, and again there was evidence for an increased absorption of glucose.

5. An attempt is made to interrelate these findings.

1. Thirty-five male cross-bred lambs at 3 d of age were given artificial milks with a protein- calorie concentration of 25 % and containing either lard, coconut fat, cottonseed oil, rapeseed oil, groundnut oil, soya-bean oil, safflower oil, tallow, maize oil or olive oil, homogenized with reconstituted skimmed cow's milk to provide 50 yo of the total energy of the diet. Two lambs were given a low-fat diet of reconstituted dried skim milk. All lambs were bottle-fed for 28 d.

2. The dietary fats and oils were highly digestible (97.2–99.5 %) with the exception of lard (89.1 %), rapeseed oil (61.9 %) and tallow (77.8 %). The indigestibility of these dietary fats was related to their content of stearic or erucic acids. The fatty acid patterns of the faecal fat were similar within each dietary group, but differed between diets.

3. Metabolic faecal fat excretion was 4.1 k0.5 g/100 g faecal dry matter. There was no similarity between the fatty acid composition of the metabolic faecal fat and that of the faecal lipids excreted by lambs given fat in their diet. The metabolic faecal fat made only a minor contribution to the total faecal lipids, so that the apparent and ‘ corrected’ digestibility coeffi-cients were very similar.

1. The fatty acid composition of the depot fats of thirty-six preruminant lambs was determined. Four lambs were slaughtered at 3 d of age, two lambs were fed on a low-fat diet for 28 d, and thirty lambs in groups of three were given ten different dietary fats in artifcial milk diets for 28 d.

2. The fatty acid patterns of the carcass fats were closely related to those of the dietary fats, and within-treatment variations were extremely low. Significant differences in fatty acid composition were observed between the skin, carcass, perinephric and subcutaneous lipids, irrespective of the diet given.

3. The carcass lipids of lambs given the low-fat diet were similar in their fatty acid composition to those of lambs aged 3 d, though the former lambs lost fat from the carcass during the experimental period.

1. Seventy-two bull calves, comprising forty-eight Ayrshire and twelve each of the Friesian and Jersey breeds, were used in a randomized block experiment. They were reared from birth on liquid diets, offered in two feeds daily, at either restricted or ad lib. levels. The restricted level of feeding was such that sufficient diet was fed to allow for a weight gain of I kg/d, and the calves given this level of feeding were slaughtered at a weight 77 kg above the mean birth weight of the breed. The calves given the diets ad lib. were slaughtered at 22 % of mature cow weight of the breed.

2. Three milk substitutes, based on spray-dried skim-milk powder, spray-dried whey powder and margarine fat, were compared. Two of these were high-protein diets (26–29 % protein) designed to contain either 20 % fat (LFHP) or 30 yo fat (HFHP) and the other was a low-protein diet (19 % protein) designed to contain 30 yo fat (HFLP).

3. Age at slaughter was lowest for diet HFHP and highest for diet HFLP. Total dry-matter intake did not differ between treatments, but daily dry-matter intake was lower on diet HFLP. Relative weight gain did not differ between diets LFHP and HFHP but was much greater than that for diet HFLP. After adjustment for differences between treatments in mean daily dry-matter intake, relative weight gain tended to be highest for diet HFHP. No difference occurred between treatments in the incidence of diarrhoea and of a high rectal temperature (> 39.33°). However, mean rectal temperature was higher for calves given the HFHP diet than for those given the HFLP diet.

4. Digestibility and nitrogen and calcium balance trials were made on six of the replications of Ayrshire calves at 4 and 10 weeks of age. Dry-matter intake at 10 weeks of age was lower for calves given diet HFLP than for those given the other diets. Apparent digestibility of fat tended to be lower for the HFLP diet. True digestibility of protein did not differ significantly between treatments. Apparent digestibility of lactose was highest for the HFLP diet.

5. No difference occurred between the two high-protein diets (LFHP and HFHP) in N or Ca retention, but N and Ca retention by calves on the low-protein diet (HFLP) was markedly lower. Daily faecal N excretion was unaffected by treatment, but daily urinary N excretion was lower and the biological value of the protein was higher for diet HFLP than for diet LFHP, with the corresponding values for diet HFHP being intermediate between the two. N reten tion/100 g weight gain was lower on diet HFLP, lower at 4 weeks of age than at 10 weeks, and lower at the restricted than at the ad lib. level of feeding at 4 weeks of age. Metabolic faecal N and endogenous urinary N at 4 weeks of age were estimated as 0.192 g/100 g dry-matter intake and 192.9 mg/kg0.72 live weight respectively.

6. Haematological findings showed that the high-fat diets (HFHP and HFLP) resulted in a slower rate of decline in packed cell volume and haemoglobin content with age. The low protein diet (HFLP) resulted in a lower rate of increase with age in the percentage of lymphocytes. Diet HFHP resulted in a decline with age in the percentage of eosinophils compared to a marked rise with the other two treatments.

7. Carcass weight did not differ between treatments, but perirenal fat deposition was much higher for the calves given the high-fat diets (HFLP and HFHP).

8. It is concluded that dietary fat is not a readily available source of energy for increasing N retention in calves given large quantities of milk substitutes, based on milk products with added fat. Unless additional fat deposition in the carcass is required, no advantages in weight

1. Twenty-four bull calves consisting of fifteen Friesians and nine Ayrshires in a randomized block experiment were reared from birth on liquid diets offered ad lib. in two feeds daily to a slaughter weight equivalent to 22 % of mature cow weight of the breed.

2. The three diets given after the calves had received 7 kg whole colostrum were (a) fresh liquid skim milk containing 0.1 % butterfat, (b) a ‘high-fat’ diet containing reconstituted spray-dried skim milk and 2.8 % margarine fat, and (c) the ‘high-fat’ diet for 14 d from birth followed by liquid skim milk. All calves received supplements of magnesium and iron, and vitamins A, D and E. Digestibility and balance trials were made on nine calves of each breed at both 4 and 10 weeks of age. Certain observations were made at slaughter.

3. Dry-matter and gross energy intakes of calves given the skim-milk diet were greater than for those given the ‘ high-fat ’ diet. Daily weight gain, efficiency of food conversion, incidence of a high rectal temperature ( > 39.33°), mean rectal temperature and faecal dry-matter content were greater for the calves given the ‘ high-fat ’ diet. Age to slaughter and incidence of diarrhoea were much greater for the calves given liquid skim milk.

4. Apparent digestibility of lactose and apparent absorption of ash and calcium were greater withthe ‘high-fat ’diet, but no difference occurred in apparent digestibility of dry matter or protein. Metabolic faecal fat excretion was estimated from the intercept of the relationship between apparently digested fat and fat intake for the calves given the liquid skim-milk diets; the values obtained ranged from 29 mg/kg live weight for Friesian calves at 10 weeks to 49.5 mg/kg for Ayrshire calves at 4 weeks. The true digestibility of the fat was estimated.

5. No difference in Ca or nitrogen retention occurred between diets, but urinary N excretion and N retention/100 g gain in weight were markedly higher and concentration of N in the urine was much lower for calves given the skim milk.

6. Perirenal fat deposition per unit of metabolic body size was 168 % greater for calves given the ‘ high-fat ’ diet. Kidney weight and skin weight were greater for the calves given the liquid skim-milk diet. The increased kidney weight was related to the very large urine output of the calves given skim milk.

7. In comparison with Ayrshire calves, Friesian calves were much less susceptible to the adverse effects of liquid skim milk, having a lower incidence of diarrhoea and faeces of a higher dry-matter content, but they did have a higher incidence of lung lesions. Friesian calves also had a higher relative growth rate, efficiency of feed conversion, mean body temperature, faecal pH, apparent absorption of Ca, retention of N and Ca per unit of metabolic body size and killing-out percentage, but lower skin weight per unit of metabolic body size. Perirenal fat per unit of metabolic body size did not differ between breeds.

1. A method is presented for estimating the incidence of protein deficiency which takes due note of the association of protein deficiency with inadequate calorie intake and is applied to the data from dietary surveys in India. It is concluded that in only about one out of ten cases does protein deficiency occur as a direct result of inadequate protein intake. In the vast majority of cases protein deficiency is the result of inadequate intake of total energy. Protein which does not bring calories with it is therefore unlikely to make any significant contribution to the solution of the protein problem in India.

2. It is shown that diets based on cereals and pulses normally consumed by the people can meet man's needs for proteinat all ages provided enough food is taken to satisfy his energy needs. It is, however, important to ensure for infants a smooth transition from breast milk to solid diets. Special care is also necessary in the case of pregnant and lactating women.

3. The nature of protein deficiency is discussed in relation to different dietary patterns. The continuity implied in the bivariate distributions of calorie and protein intake is seen to provide a possible explanation of the experimental results on the development of kwashiorkor observed in animals on a diet short of both calories and protein and ondietspredominantly short of protein.

1 The continuous faecal marker chromic oxide, Cr2O3, and the intermittent marker brilliant blue were used together in metabolic balance studies of calcium and magnesium in two young women.

2. Faecal output was derived by four methods: no marker, brilliant blue, Cr2O3, or both brilliant blue and Cr2O3.

3. Balances of Ca and Mg derived by the four methods of obtaining faecal output were compared.

4. Recovery of ingested Cr2O3 in the faeces appeared complete in experiments on three further subjects, with only a negligible amount being excreted in the urine.

5. Simultaneous use of both types of marker is recommended for short-term balance studies of nutrients such as Ca and Mg which are not readily absorbed.

1. Pigs were weaned from the sow at 2 d of age and reared on a diet of cow's milk supplemented with vitamin D, and antibiotics. The effects of four levels and two frequencies of feeding, and the temperature of the environment were studied in relation to the performance of the pigs and the digestion of the milk protein. Pigs fed at the two lower levels receivedadiet of cow's milk, but at the two higher levels cow's milk was spray-dried and reconstituted to 20% total solids. A comparison was also made between cow's milk and spray-dried reconstituted milk, both fed hourly with 12.5% total solids. The pigs were slaughtered at 28 d of age.

2. No differences in the nutritive value or digestion of the milk protein were found when cow's milk and reconstituted milk were fed with a total solids content of 12.5 yo.

3. Increasing the level of feeding resulted in a faster growth rate, and some deterioration in the feed conversion efficiency. The growth rate of the pigs from 2to 28 d of age when fed at a high level greatly exceeded that of sucking pigs reared on the sow. The retention of the dietary nitrogen also improved with increased feed intake. A highly significant inverse linear correlation of N retention with age was found at all levels of feeding. The milk protein was efficiently digested at all levels of feeding.

4. The mortality rate was very low but there appeared to be some association of losses with a high level of feeding during the first few days of life.

5. Feeding hourly compared with feeding twice daily improved the feed conversion efficiency, although the effect on growth rate and N retention was small. The retention of digesta in the stomach appeared to be an important factor in the regulation of the amount of digesta in the small intestine and in the maintenance of digestive efficiency. The stomachs of pigs fed twice daily contained considerably greater amounts of digesta than those of pigs fed at hourly intervals. There was little difference in the amount and composition of digesta in the small intestine and caecum at either frequency of feeding.

6. No differences were found in the performance of the pigs, N retention or the efficiency of digestion of the milk protein when the environmental temperature was maintained either at zoo throughout the experiment, or at 30' gradually reducing to zoo during the first 14d.

1. The intake and excretion of total nitrogen, fat and the various forms of carbohydrate, and the heats of combustion of the diet, urine and faeces were measured in groups of young men, young women, elderly men and elderly women.

2. Each group was studied while the subjects were eating two diets in turn, which differed in their contents of unavailable carbohydrate; the young women were also studied on a third diet which was rich in unavailable carbohydrate.

3. Increasing the intake of unavailable carbohydrate resulted in a greater faecal loss of energy, and in most instances of nitrogen and fat.

4. There was no significant effect of sex or age on the apparent digestibility of protein, fat or available carbohydrate.

5. The results are used to evaluate the use of calorie conversion factors for calculating the metabolizable energy content of mixed diets.

6. These show that for practical purposes the classical Atwater factors can be used to calculate the metabolizable energy of a diet with reasonable accuracy, provided that when available carbohydrate (as monosaccharides) values are used in the calculation a factor of 3.75 kcal/g (15.7 kJ/g) is used.

7. The studies demonstrate that the accuracy of any method for calculating the metabolizable energy of a diet is largely determined by the accuracy with which the method is capable of predicting the gross energy of the diet.

1. The serum glycerides of men were raised 1–2.5 h after the ingestion of glycerol, whereas in young women given glycerol the serum glycerides were not raised. In men who had a supplementation of glycerol to their free-choice diet there was a rise in the concentration of fasting serum glycerides, a rise that was not found when a similar supplementation was given to young women.

2. These findings would support the tentative suggestion that dietary fructose does not follow the Emden-Meyerhof pathway to the same extent as glucose. The increased serum glyceride levels reported after high-fructose diets may be due to an increased availability of the glycerol moiety of glycerides.

1. Concentrations of nucleic acid nitrogen (NA-N) and other nitrogenous constituents were estimated in samples of rumen fluid taken from calves and cows which were either given stall diets of varying nitrogen content or were allowed to graze pasture. Concentrations of NA-N ranged from 1.5 to 27.5 mg/100 g water.

2. Ratios of RNA: DNA in rumen fluid were similar to those in rumen bacteria and were not related to those in the diets. Pure nucleic acids added to the rumen were rapidly degraded. It was therefore concluded that NA-N in rumen fluid was largely of microbial origin and provided an index of total microbial nitrogen.

3. In most experiments, with an individual animal consuming diets of various nitrogen contents, NA-N formed a fairly constant percentage (8-15 for different animals) of the total non-ammonia nitrogen in rumen fluid. This suggested that nitrogen entering the rumen fluid limited microbial growth. Consumption of a diet containing extracted decorticated groundnut meal (diet B), however, led to lower values for this percentage than did the other diets. Diet B was also exceptional in leading to marked diurnal variations in NA-N concentrations in rumen fluid, suggesting a cyclic fluctuation in the size of the microbial population.

4. Comparison of NA-N:total nitrogen ratios in rumen fluid and bacteria suggested that, for all the diets except diet B, 55–80 and 40–50% of the non-ammonia nitrogen in rumen fluid was of microbial origin for the calves and cows respectively.

1. The concentrations of individual free serum amino acids have been studied during the course of chronic protein malnutrition in experimentally malnourished pigs.

2. Until growth was markedly impaired, reducing the protein content of the diet had no significant effect on serum amino acid composition.

3. During the period when growth had practically ceased but kcal intake per kg body-weight was normal the concentrations of valine, leucine, isoleucine, threonine and eventually tyrosine fell, the levels of alanine and serine were above control levels and aspartic acid, glycine, methionine, phenylalanine, proline, arginine, histidine and lysine remained unaltered.

4. When the kcal intake per kg fell below control levels, owing to anorexia, and the animals began to lose weight, the levels of alanine, glycine, serine and methionine fell and valine, leucine, isoleucine, threonine and tyrosine remained well below control levels.

5. The physiological, nutritional and metabolic significance of these findings is considered. The changes in alanine and glycine concentration are discussed in terms of the regulation of gluconeogenesis. The reduction of the branched-chain amino acids is interpreted on the basis of their availability for synthetic and catabolic needs.

1. The energy values of the diets of twenty-three women who were breast-feeding and thirty-two who were bottle-feeding their babies were determined by 7 d weighed surveys. All the subjects were healthy and living at home, and their babies were thriving. The lactating mothers took, on average, 591 kcal (2.5 MJ)/d more than those who were not lactating.

2. Both groups were losing weight, on average. The estimated contribution of such losses to the total energy supply was added to and the amounts expended on basal metabolism deducted from the dietary energy intakes. Since the activity of each group was fairly similar, it was possible to conclude that the average amount of energy available to support lactation was 618 kcal (2.6 MJ) daily. The average energy value of the milk produced was estimated from the weights of the babies to be 597 kcal (2.5 MJ) daily.

3. Critical evaluation of those averages, and of the assumptions on which they were based, led to the conclusion that the energy exchanges in human lactation have an efficiency of 90% or more, with a lower limit of about 80%.

4. The additional supply of 600 kcal (2.5 MJ) in the daily diet should suffice to support lactation and a ‘round figure’ of 500 kcal (2.1MJ) daily may be regarded as reasonable in official recommended allowances.

1. Hypertryptophanaemia, hypertryptophanuria and to a lesser degree a generalized hyperaminoaciduria were observed in phenylketonuric patients receiving certain commercial low-phenylalanine diets containing DL-tryptophan.

2. The generalized hyperaminoaciduria was associated with the ingestion of acid hydro-lysates of protein, but not with the ingestion of enzymic hydrolysates or D-tryptophan.

3. Alanine recovered from the urine of these treated patients had a D-isomer content of approx. 50%. This amount of urinary D-alanine could be derived from the ingestion of an acid hydrolysate of protein in which the amino acids had racemized to the extent of 2–3%.

1. Groups of female albino rats were given 12–20 mg of one of the eight known toco-chromanols in 0.2 ml arachis oil by stomach tube, and were killed 2, 4, 8, 16 or 24 h afterwards. The liver, spleen, heart, kidneys, brain, small intestine and a portion of striated muscle were removed from each rat and analysed for the tocochromanol given.

3. Maximum levels of the tocochromanols occurred in most tissues 4–8 h after dosing. In the liver the tocopherols were more efficiently absorbed than were the corresponding toco-trienols. In kidney, heart and muscle the percentage uptake of the tocotrienols was often greater than that of the corresponding tocopherols.