To explore the regulation of the acute phase response in vivo, the effects of pentoxifylline (PX) treatment (100 mg/kg ip 1 h before infection) were investigated in infected and pair-fed rats 2 and 6 days after an intravenous injection of live bacteria ( Escherichia coli). PX treatment prevented the increase in plasma tumor necrosis factor (TNF)-α (peak 1.5 h after the infection) and resulted in an 84 and 61% inhibition of plasma interleukin (IL)-1β and IL-6, respectively (peaks at 3 h). Plasma corticosterone kinetics were not modified by the treatment. Infection increased α1-acid glycoprotein (AGP), α2-macroglobulin (A2M), and fibrinogen plasma concentrations and decreased albumin levels. PX significantly reduced AGP plasma concentration as early as day 2 in infected animals but reduced A2M and fibrinogen plasma levels only at day 6. The treatment had no effect on the albumin plasma concentration. Hepatic AGP and fibrinogen mRNA levels increased in infected rats, whereas those of A2M were unchanged and those of albumin were decreased. Two days after infection, AGP and fibrinogen mRNA levels were reduced in treated infected animals. PX was ineffective in modifying those of A2M and albumin. These data demonstrate, in vivo, that different acute phase proteins are individually regulated in sepsis. The in vivo effects of PX treatment support the hypothesis that TNF-α plays an important role in the regulation of AGP production, whereas other factors seem to be involved in the regulation of A2M, fibrinogen, and albumin expression.

The central role of the ubiquitin‐proteasome system in the loss of skeletal muscle protein in many wasting conditions has been well established. However, it is unclear what factors are responsible for the suppression of this system during periods of protein gain. Thus, the aim of these studies was to examine the short‐term effects of insulin release and nutrients on skeletal muscle protein turnover in young rats starved for 48 h, and then infused intravenously with amino acids (AA), or fed an oral diet. Forty‐eight hours of starvation (i.e. prolonged starvation in young rats) decreased muscle protein synthesis and increased proteasome‐dependent proteolysis. Four‐hour AA infusion and 4 h of refeeding increased plasma insulin release and AA concentrations, and stimulated muscle protein synthesis, but had no effect on either total or proteasome‐dependent proteolysis, despite decreased plasma corticosterone concentrations. Both muscle proteasome‐dependent proteolysis and the rate of ubiquitination of muscle proteins were not suppressed until 10 h of refeeding. The temporal response of these two measurements correlated with the normalised expression of the 14‐kDa E2 (a critical enzyme in substrate ubiquitination in muscle) and the expression of the MSS1 subunit of the 19S regulatory complex of the 26S proteasome. In contrast, the starvation‐induced increase in mRNA levels for 20S proteasome subunits was normalised by refeeding within 24 h in muscle, and 6 h in jejunum, respectively. In conclusion, unlike protein synthesis, skeletal muscle proteasome‐dependent proteolysis is not acutely responsive in vivo to insulin, AA, and/or nutrient intake in refed starved rats. This suggests that distinct and perhaps independent mechanisms are responsible for the nutrient‐dependent regulation of protein synthesis and ubiquitin‐proteasome‐dependent proteolysis following a prolonged period of catabolism. Furthermore, factors other than the expression of ubiquitin‐proteasome pathway components appear to be responsible for the suppression of skeletal muscle proteasome‐dependent proteolysis by nutrition.

The metabolism and the rate of transfer of cortisol across the placenta in pregnant guinea-pigs and foetuses were studied by constant intravenous infusions of tritium-labelled cortisol. Estimates of endogenous and radioactive plasma cortisol levels were used to calculate the following parameters at four stages before parturition (days 62, 64, 66 and 67; parturition occurring at day 68): metabolic clearance rate; production rate; adrenal secretory rate; transfer rate from mother to foetus and from foetus to mother; irreversible removal rate; the fraction of cortisol derived from the other in the foetal and maternal vascular compartments; the fraction of secreted and recycled cortisol involved in the transfer. The metabolic clearance rate and the rates of production and secretion of cortisol were higher in the mother than in the foetus between days 62 and 67 of gestation. About 90% of the foetal cortisol was of maternal origin. The fraction of maternal cortisol of foetal origin increased in the last days of gestation.

The concentrations of corticosterone and aldosterone in the plasma and adrenal glands of foetal, newborn and mother mice were estimated during the last 4 days of pregnancy and throughout the perinatal period. The level of corticosterone in the maternal and foetal plasma fell from day 17 of gestation until birth, and then remained stable. Whereas the corticosterone content of the maternal adrenal glands did not change significantly, that of the foetal adrenal glands reached a peak on day 19 of gestation. At every stage of gestation, the level of corticosterone in the maternal plasma was higher than that in the foetus. Changes in the concentration of aldosterone in the foetal plasma and adrenal glands were similar and characterized by peak values at birth. In the mother during the last 4 days of pregnancy, the level of aldosterone in the plasma was higher than in non-pregnant mice, but lower than that in the foetus.

Abstract. Ovine corticotrophin-releasing factor (oCRF) (1 μg/kg) and arginine vasopressin (AVP) (1 μg/kg) were injected iv in sheep, both separately and in combination. Plasma levels of immunoreactive ACTH (IRACTH), cortisol, and aldosterone were measured for 3 h after the injections. Mean levels before injections were 8 ± 4 pmol/l for ACTH, 7 ± 3 nmol/l for cortisol, and 28 ± 9 pmol/l for aldosterone. CRF caused a rapid rise in IR-ACTH and a peak level of 125 ± 52 pmol/l was obtained 15 min after injection. Highest values for cortisol and aldosterone levels were 40 ± 9 nmol/l and 64 ± 13 pmol/l, respectively, 30 min after injection. AVP also increased IR-ACTH (maximum level: 202 ± 77 pmol/l at 5 min) and aldosterone (128 ± 36 pmol/l at 15 min), whereas the cortisol increase was lower than after CRF. Simultaneous injection of CRF and AVP produced an addition of the IR-ACTH response (295 ± 82 pmol/l at 15 min), but the changes in cortisol levels were similar to those obtained after CRF alone and those in aldosterone levels resembled those induced by AVP alone. Plasma Na and K, osmolality, and plasma renin activity (PRA) were not modified by either CRF or AVP. It is suggested that the increase in aldosterone levels after CRF could be mediated by ACTH and that after AVP by an IR-ACTH peptide with less effect on cortisol secretion.

SUMMARY Concentrations of cortisol and corticosterone in the plasma and adrenal glands of male and female guinea-pigs were estimated throughout the first postnatal day and thereafter at intervals up to 3 weeks of age. In the guinea-pig, the basal level of cortisol secretion is established more slowly than in other species. The concentration of plasma cortisol is very high at birth, with a marked fall between days 1 and 10 post partum and then a steady level from day 10 to 20, the time of weaning. At day 10 the values for plasma cortisol and corticosterone approach the lower ones found in the adult. There were peaks in the amounts of corticosteroids found in the adrenal gland at 50 h, 4 and 7 days and these may have been due to increased hormonal synthesis between days 2 and 8.

Concentrations of cortisol, corticosterone and cortisone in the plasma and adrenal glands, liver glycogen and plasma glucose of foetal, newborn and mother guinea-pigs were estimated during the last 6 days of pregnancy and throughout the first 24 h post partum. At the same time progesterone was measured in the plasma of the mother. During the prepartum rise in foetal plasma cortisol levels and liver glycogen, no significant change in the foetal adrenal cortisol content was observed. The plasma and adrenal cortisol concentrations of the mother were much higher than those observed in the foetus and increased significantly before parturition. In the mother as in the foetus, cortisone and corticosterone represent only a small percentage of corticosteroids compared with cortisol. These results indicate that the autonomous capacity of foetal adrenals, inhibited by maternal secretions before term, appears suddenly at birth.

To investigate the relationships between maternal, umbilical cord and piglet fatty acid status, multiparous sows (six per diet) were fed on diets containing supplements (30 g/kg) of either soyabean oil or tuna oil for the last 21 d of pregnancy. The proportions of most fatty acids differed between diets: in particular, the tuna-oil-containing diet supplied more 22:6n-3 and less 18:2n-6 fatty acids than the soyabean-oil-containing diet. Maternal plasma fatty acid concentrations (mg/l) were greater than those in umbilical plasma and 20:4n-6 and 22:6n-3 fatty acids were present in higher proportions (g/100 g fatty acids) in umbilical than maternal plasma. Feeding tuna oil increased the proportionate amounts (g/100 g fatty acids) of total n-3 fatty acids (particularly 22:6n-3) in umbilical cord, plasma and piglet tissues compared with feeding soyabean oil: in contrast, the proportion of 20:4n-6 was decreased by feeding tuna oil. Changes in piglet fatty acid proportions as a result of oil feeding were not influenced by piglet weight. While proportions of the long-chain n-3 and n-6 polyunsaturated fatty acids in piglet liver, spleen and reproductive tract (ovaries plus uterus of the female, testes of the male) correlated well with those of umbilical plasma, those in brain and retina were poorly correlated. Therefore umbilical plasma cannot be used to predict the fatty acid status of piglet brain.