AimN-acyl dopamines (NADD) are gaining attention in the field of inflammatory and neurological disorders. Due to their hydrophobicity, NADD may have access to the endoplasmic reticulum (ER). We therefore investigated if NADD induce the unfolded protein response (UPR) and if this in turn influences cell behaviour.MethodsGenome wide gene expression profiling, confirmatory qPCR and reporter assays were employed on human umbilical vein endothelial cells (HUVEC) to validate induction of UPR target genes and UPR sensor activation by N-octanoyl dopamine (NOD). Intracellular ATP, apoptosis and induction of thermotolerance were used as functional parameters to assess adaptation of HUVEC.ResultsNOD, but not dopamine dose dependently induces the UPR. This was also found for other synthetic NADD. Induction of the UPR was dependent on the redox activity of NADD and was not caused by selective activation of a particular UPR sensor. UPR induction did not result in cell apoptosis, yet NOD strongly impaired cell proliferation by attenuation of cells in the S-G2/M phase. Long-term treatment of HUVEC with low NOD concentration showed decreased intracellular ATP concentration paralleled with activation of AMPK. These cells were significantly more resistant to cold inflicted injury.ConclusionsWe provide for the first time evidence that NADD induce the UPR in vitro. It remains to be assessed if UPR induction is causally associated with hypometabolism and thermotolerance. Further pharmacokinetic studies are warranted to address if the NADD concentrations used in vitro can be obtained in vivo and if this in turn shows therapeutic efficacy.

An experiment, involving 68 female pigs, was undertaken to measure the effects of two diets differing in protein content, and of two patterns of feeding. The animals were housed in an enclosed building. The experiment extended through several parities; culled sows were replaced by gilts during the experiment, the whole course of which lasted 5 years.The diets were given at the rate of 1-8 or 2-3 kg per day throughout gestation, but the rate was reversed during the 5-week lactation so that, for litters of eight to nine pigs sows in each treatment group received the same quantity of food per parity. As a result of unsatisfactory performance, dietary composition was changed after 2 years so that for the last 3 years the digestible energy contents were higher.Treatments significantly influenced gestation live-weight gain, lactation weight loss and gestation backfat gain. The lower rate of gestation feeding was associated with low or negative gestation weight increases after the third to fourth litters, and a greater apparent rate of decline with increasing age in birth and 3-week weight per piglet. The high gestation, low lactation, rates of feeding led to slightly greater litter size and lower weaning weights per pig. A daily intake of 208 g crude protein and 8'3 g lysine appeared to meet the sow's requirements throughout gestation.In the pregnant sow feeding area, winter air temperatures were on average 16 °C below those in the summer, but were rarely below freezing point. Winter backfat gain was lower than, and gestation gain only half that in the summer. Litter size was also greater following summer pregnancies and 3-week weight per pig was greater following winter pregnancies. Independent of litter size, birth and 3-week weight per pig were positively correlated with gestation gain within treatment and season. The apparent positive correlation of litter size at 3 weeks with gestation backfat and weight gain was not found at birth. Litter size at birth was negatively correlated with gestation gain within season. The percentage of fertile matingswas less for matings between 1 September and 31 January. This coincided approximately with the reduced litter size (alive) which occurred following winter gestations.Lactation weight loss and 3-week weight per pig declined with increasing age of sow and the degree of weight loss was unrelated to subsequent litter size.The apparent effect of seasons and treatments on litter size at birth appeared not to be an obvious function of changes in live weight, which were also marked between seasons and treatments, but level of food intake in early gestation may have affected litter size independently. It was concluded that birth weight especially in the older sows, was associated with the rate of food intake in gestation, and possibly also in lactation, and with gestation empty weight gain.

SUMMARYWeaner Hampshire × Landrace × Large White (Hampshire cross) and Landrace × Landrace × Large White (Landrace cross) pigs were given combinations of three diets differing in crude protein content (high: H, low: Land very low: vl). Hampshire cross pigs at 90 kg, both under ad libitum and restricted feeding had greater rates of gain and eye muscle measurements and shorter carcasses than Landrace cross pigs, but were fatter after ad libitum feeding and more efficient food converters after restricted feeding. The HLL treatment led to improved gain and food conversion compared to the LLH or LLL treatment, whereas the LLH treatment led to larger eye muscle measurements. The LvlH treatment led to greater efficiency and eye-muscle area than treatment Lvlvl at 114 kg. An economic analysis was carried out to assess the relative profitability of slaughtering at a range of live weights. Curves were fitted to the data on food intake and live weight. Values were assumed for major costs, and a seven-day interval was allowed between batches of pigs. The calculations indicated that the H diet led to a slight increase in monetary return per pig per day when it was given in the post-weaning period to pigs fed to a scale. Although the Hampshire cross pigs showed a response to the H diet in the finishing period when slaughtered either at 90 or 114 kg, their calculated return was not increased. Ad libitum feeding led to a greater return for heavy but not, on average, for bacon pigs. Maximum return occurred at slaughter between 70 and 115 kg live weight and was only margin-ally greater for restricted baconers at 90 kg than for ad libitum heavy pigs at 110–115 kg. However, return as a percentage of working plus fixed capital was greater for baconers, but the ratio rose throughout the range of hypothetical slaughter weights in both groups. In-clusion of the cost of borrowing money had a negligible effect on the slaughter weight for maximum return with pigs managed in batches.

SUMMARYGestating female pigs received either a low or a high intake per day of diets containing either a low or high protein concentration. A change in the composition of both diets occurred after 2 years, when the protein quality of the high protein diet was improved and the energy content of both diets was increased. Vitamin A determinations were carried out on 245 piglet livers and 32 pairs of kidneys and lungs at birth from 47 sows. The livers, kidneys and lungs of 16 sows were also analysed for vitamin A after approximately 4 years on experiment. Vitamin A was detected at birth with antimony trichloride in the liver of the piglet, but not in the kidney or lung. The sow's kidney was found to contain only small amounts and lung tissue only traces.A dietary vitamin A level of 4800 i.u./kg during the breeding life of healthy sows, or 8600 i.u./day during gestation, was adequate from the point of view of both a constant storage in piglet livers at birth over eight to ten parities and a relatively high concentration remaining in sow livers after that period. This conclusion is in line with recommendations of the Agricultural Research Council (1966).As a consequence of differences in both the condition of the sows and in their responses in the two periods, the results for each period are presented separately. In the first 2-year period, when the sows received a relatively low intake of dietary protein during gestation (between 248 and 317 g protein/sow/day), and a low energy intake; that is, when protein was used for energy production, the liver vitamin A storage of the piglet at birth was increased by raising either the daily protein intake during gestation to 352 g, or the food intake from 1·8 to 2·3 kg/sow/day. Liver vitamin A and N concentrations were negatively correlated with liver weight, but increasing dietary protein concentration raised liver weight and its vitamin A content. Liver vitamin A per piglet was not affected by litter size.A conclusion may not be drawn concerning the contribution of dietary energy to the differences in response between periods, because in addition to dietary changes other differences occurred between periods. Nevertheless, in the second 2-year period, when energy intake during gestation was adequate for normal growth and development, a difference of 150 g in protein intake/sow/day (363 g against 208 g) had no effect on liver weight or its vitamin A content. Furthermore, there was no significant treatment effect on total protein or albumin concentrations in the serum of the sow.