The interactions between acetate or ethanol metabolism, lipogenesis, and ketone body utilization have been studied in isolated livers from fed rats perfused with 15 mM glucose and 10 mM acetate or ethanol. The contribution of acetate to ketogenesis is constant; on the other hand, the contribution of ethanol to ketogenesis increases with time, presumably because of the accumulation of acetate in the perfusate. Ketogenesis is decreased in the presence of ethanol (but not acetate), while ketone body utilization is not affected by ethanol or acetate. Acetate contributes one third and ethanol contributes one half of the carbon incorporated into fatty acids and 3-beta-hydroxysterols. Only a small fraction (less than 5%) of the incorporation of acetate or ethanol into fatty acids and sterols occurs via transient incorporation into ketone bodies.
1 Muscle paresis and aberrant pharmacological responses are two important pathophysiological changes that have been observed at the neuromuscular junction following thermal injury. By use of the mouse model of 20%, 30% and 50% total body surface area (BSA) burn, we examined the significance of intracellular mediators, adenosine 3': 5'-cyclic monophosphate (cyclic AMP) and prostaglandin E2 (PGE2) in perturbing the physiological function of tension development and the pharmacological response to (+)-tubocurarine (+)-Tc at day 21 post-burn.2 Cyclic AMP levels increased with the size of burn. The relationship between mean cyclic AMP levels and burn size was significant (R2 = 0.96, r = 0.98). Significant (P < 0.05) reductions in tension development (g) were observed for the 30% and 50% BSA burn group compared to controls (30.3 + 8.3 and 34.1 + 5.9 vs 59.1 1.0, respectively). Tension alterations were associated with increased cyclic AMP levels; the relationship between increased cyclic AMP levels and tension decrease was significant (R2 = 0.82, r = 0.91). The dose of (+)Tc required to inhibit twitch tension increased in proportion to burn size and was statistically significant in the 50% BSA burn group compared to controls (0.3320 + 0.09 vs 0.1093 + 0.11 mg kg-1, P < 0.05). The alterations in the effective dose of (+)-Tc were significantly correlated to increases in cyclic AMP levels (R2 = 0.70, r = 0.83). Although PGE2 levels were elevated in the 30% and 50% burn groups, no relation was seen to either tension or (+ )-Tc doses. 3 These studies, therefore, support the hypothesis that cyclic AMP plays a significant role in physiological and pharmacological responses in skeletal muscle following thermal injury.
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