Palmitic acid kinetics in fasting, traumatized patients.

The contribution of free fatty acid oxidation to the elevation in energy expenditure after trauma has not been well characterized. Six control subjects and six traumatized patients were fasted for 48 hours and given a primed continuous infusion of (1-14C)palmitate to measure plasma palmitate and total free fatty acid kinetics. Traumatized patients had greater urinary nitrogen losses (20.8 vs. 9.3 g N per day) and a significantly greater ratio of measured to predicted resting energy expenditure (+36% vs. -6%) compared with controls. Individual and total plasma free fatty acid concentrations were similar for the two groups. The turnover and oxidation of plasma palmitate and total free fatty acids were not changed by multiple trauma. These results demonstrated that plasma free fatty acids and palmitate do not contribute to increased energy expenditure following trauma.     

Feeding the rat intravenously with ketone bodies following colon anastomosis

Ketone bodies are an important metabolic fuel for the gastrointestinal system and as a consequence may promote colonic healing. Ketone bodies and glucose were compared in a dose dependent manner as nonprotein fuels for support of resected colon. Rats had their descending colons resected and received all nutrients by vein for 5 days postoperation. Colonic healing was evaluated from the air pressure required to break the wound. All rats received constant nutrients except for non-protein energy which was fed at 10.5, 21, 31.5, and 42 kcal/day using either glucose or monoacetoacetin as substrate. Colonic bursting pressure was measured on day 5 after surgery. When energy intake was 21 kcal/day or greater, the bursting pressure was two-thirds of nonwounded tissue and was independent of energy quantity and source. At 10.5 kcal/day, bursting pressure for glucose-fed animals was similar to that for animals with no added nonprotein energy while, in contrast, bursting pressure for animals fed monoacetoacetin was similar to that for animals fed 42 kcal/day. It was concluded that bursting pressure was influenced by dietary intake only if the energy intake was sufficiently low, and then ketone bodies were better than glucose for support of colonic healing.     

Toxicity of ammonium perfluorooctanoate in male cynomolgus monkeys after oral dosing for 6 months.

Ammonium perfluorooctanoate (APFO) is a processing aid in the production of fluoropolymers that has been shown to have a long half-life in human blood. To understand the potential toxicological response of primates, groups of male cynomolgus monkeys were given daily po (capsule) doses of either 0, 3, 10, or 30 (reduced to 20) mg/kg/day for 26 weeks. Two monkeys from each of the control and 10 mg/kg/day dose groups were observed for 90 days after the last dose. Clinical observations, clinical chemistry, determination of key hormones, gross and microscopic pathology, cell proliferation, peroxisomal proliferation, bile-acid determination, and serum and liver perfluorooctanoate (PFOA) concentrations were monitored. Toxicity, including weight loss and reduced food consumption, was noted early in the study at the 30 mg/kg/day dose; therefore, the dose was reduced to 20 mg/kg/day. The same signs of toxicity developed in 3 monkeys at 20 mg/kg/day, after which treatment of these monkeys was discontinued. One 30/20 mg/kg/day monkey developed the signs of toxicity noted above and a possible dosing injury, and this monkey was sacrificed in extremis on Day 29. A 3 mg/kg/day dose-group monkey was sacrificed in extremis on Day 137 for reasons not clearly related to APFO treatment. Dose-dependent increases in liver weight as a result of mitochondrial proliferation occurred in all APFO-treated groups. Histopathologic evidence of liver injury was not observed at either 3 or 10 mg/kg/day. Evidence of liver damage was seen in the monkey sacrificed in moribund condition at the highest dose. Body weights were decreased at 30/20 mg/kg. PFOA concentrations in serum and liver were highly variable, were not linearly proportional to dose, and cleared to background levels within 90 days after the last dose. A no observable effect level was not established in this study, and the low dose of 3 mg/kg/day was considered the lowest observable effect level based on increased liver weight and uncertainty as to the etiology leading to the moribund sacrifice of one low-dose monkey on Day 137. Other than those noted above, there were no APFO-related macroscopic or microscopic changes, changes in clinical chemistry, hormones, or urinalysis, or hematological effects. In particular, effects that have been associated with the development of pancreatic and testicular toxicity in rats were not observed in this study.