A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions.

Two studies were conducted to determine if dysprosium (Dy) could be used as a quantitative fecal marker for studies of zinc-70 (70Zn), copper-65 (65Cu) and magnesium-26 (26Mg) absorption in humans. In the first experiment, Dy excretion was shown to be complete (104 +/- 9%; mean +/- SD, n = 6) and the kinetics of fecal Dy excretion closely paralleled that of 70Zn but not 65Cu. Because of the similarity in 70Zn and Dy excretion kinetics, a method for estimating 70Zn absorption was developed which used 70Zn and Dy data from only the first two stools passed after isotope administration. Average estimates of 70Zn absorption based on the two-stool (partial pool) vs total pool (5-day composite) method were not different (28.0 +/- 5.2 vs 24.4 +/- 4.1%, respectively; means +/- SEM; p > 0.10). In the second study, the same questions was addressed relative to 26Mg absorption. 26Mg and Dy also exhibited nearly identical excretion patterns. Average estimates of 26Mg absorption based on the partial pool vs total pool method were comparable yielding mean values of 22.7 +/- 3.4 vs 23.2 +/- 2.5% and 26.1 +/- 1.8 vs 24.3 +/- 1.8%, respectively, from magnesium-26 oxide (26MgO) and 26Mg glycinate. Advantages and limitations of the partial pool method for estimating mineral absorption are discussed.

Rats of synthesis and degradation in vivo of collagens in 0.5 M-acetic acid-soluble and -insoluble extracts from skins of three growing rats were determined by using a labelling procedure involving exposure of the animals to an atmosphere of 18O2 for 36 h. For comparison, rats also received injections of [2H]proline. Serial skin biopsies were taken at frequent intervals over 392 days. Enrichment of 18O and 2H in the hydroxyproline of the collagen fractions was determined by gas chromatography-mass spectrometry. Changes in size of the soluble and insoluble collagen pools were considered in the evaluation of isotope kinetic data. The insoluble collagen fraction showed no degradation. The efflux (mean +/- S.D., expressed as mumol of hydroxyproline) from the soluble collagen pool was estimated to be 59.9 +/- 1.9 per day from the 18O data, and 25.5 +/- 7.5 per day from the 2H results. The finding indicates significant reutilization of 2H-radiolabelled proline for hydroxyproline synthesis. From these isotope data and estimates of size of the collagen pools it was determined that 55% of the collagen disappearing from the soluble pool was due to maturation into insoluble collagens and 45% of the disappearance was a result of actual degradation of soluble collagen. These results confirm the utility of 18O2 as a non-reutilizable label for studies of collagen turnover in vivo.

The tolerance of human subjects to two microfungal food products was studied in separate double-blind cross-over studies. As an addition to the subject's usual diets, cookies with and without 20 g of a product from Fusarium graminearium were fed to a group of 100 individuals daily. In a second study, cupcakes with and without 10 g of Paecilomyces variotii were given daily to 50 individuals. Mild rashes possibly related to one of the microfungal food products occurred in two individuals fed P variotii. Except for a decrease in serum cholesterol during the F graminearium study, no significant changes were noted in 17 serum constituents. During nutritive value studies, digestibility, biological value, and net protein utilization were calculated for the two microfungal proteins and for milk. The values for milk were 95, 85, and 80%, respectively. The values for F graminearium were 78, 84, and 65%, respectively. For P variotii corresponding figures were 81, 67, and 54%. On the basis of these results both microfungal foods may be deemed safe for human consumption at the levels tested.

Data from nitrogen balance studies in young men and elderly women were analyzed for the pattern of urinary nitrogen excretion after the subjects had changed from an adequate to an essentially protein-free diet. The single exponential equation: y = P1e-p2t+P3, provided an adequate fit of the data, suggesting that a single-pool model describes the adaptive decline in urinary nitrogen excretion under these dietary conditions. Comparisons of the estimated parameters showed that the fractional rate constant, P2, was the same for both the young men and elderly women, but that the other coefficients differed between the two groups depending upon whether they were expressed per day, per kg of body weight, per unit creatinine excreted, or per kg of body cell mass. The length of time between the change in diet and the attainment of a new equilibrium in urinary nitrogen excretion (ts, or time to stability) is defined as ts = 1/p2 loge(p1/s) where s is the standard error of the fit. The average time to stability was the same in both groups (4.5 days), and 95% of the subjects reached the new equilibrium in nitrogen output within 8 days.