Periocular ulcerative dermatitis associated with gentamicin ointment prophylaxis in newborns.

A recent shortage of erythromycin ointment has resulted in the use of alternative agents for newborn ocular infection prophylaxis in the United States. We report a series of 26 newborns in whom a characteristic periocular ulcerative dermatitis developed after gentamicin ointment administration at 2 Philadelphia hospitals.

Impaired oxidative phosphorylation in hepatic mitochondria in growth-retarded rats.

Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in adulthood. We have developed an IUGR model in the rat whereby the animals develop diabetes between 3 and 6 mo of age that is associated with insulin resistance. Alterations in hepatic glucose metabolism are known to contribute to the hyperglycemia of diabetes; however, the mechanisms underlying this phenomenon have not been fully explained. To address this issue, intact liver mitochondria were isolated from IUGR and control offspring at different ages to examine the nature and time course of possible defects in oxidative metabolism. Phosphoenolpyruvate carboxykinase (PEPCK) expression was also measured in livers of IUGR and control offspring. Rates of ADP-stimulated (state 3) oxygen consumption were increased for succinate in the fetus and for alpha-ketoglutarate and glutamate at day 1, reflecting possible compensatory metabolic adaptations to acute hypoxia and acidosis in IUGR rats. By day 14, oxidation of glutamate and alpha-ketoglutarate had returned to normal, and by day 28, oxidation rates of pyruvate, glutamate, succinate, and alpha-ketoglutarate were significantly lower than those of controls. Rotenone-sensitive NADH-O2 oxidoreductase activity was similar in control and IUGR mitochondria at all ages, showing that the defect responsible for decreased pyruvate, glutamate, and alpha-ketoglutarate oxidation in IUGR liver precedes the electron transport chain and involves pyruvate and alpha-ketoglutarate dehydrogenases. Increased levels of manganese superoxide dismutase suggest that an antioxidant response has been mounted, and hydroxynonenal (HNE) modification of pyruvate dehydrogenase E2-(catalytic) and E3-binding protein subunits suggests that HNE-induced inactivation of this key enzyme may play a role in the mechanism of injury. The level of PEPCK mRNA was increased 250% in day 28 IUGR liver, indicating altered gene expression of the gluconeogenic enzyme that precedes overt hyperglycemia. These results indicate that uteroplacental insufficiency impairs mitochondrial oxidative phosphorylation in the liver and that this derangement predisposes the IUGR rat to increased hepatic glucose production by suppressing pyruvate oxidation and increasing gluconeogenesis.

Impaired oxidative phosphorylation in skeletal muscle of intrauterine growth-retarded rats.

Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in later life. We have developed a model of uteroplacental insufficiency, a common cause of intrauterine growth retardation, in the rat. Early in life, the animals are insulin resistant and by 6 mo of age they develop diabetes. Glycogen content and insulin-stimulated 2-deoxyglucose uptake were significantly decreased in muscle from IUGR rats. IUGR muscle mitochondria exhibited significantly decreased rates of state 3 oxygen consumption with pyruvate, glutamate, alpha-ketoglutarate, and succinate. Decreased pyruvate oxidation in IUGR mitochondria was associated with decreased ATP production, decreased pyruvate dehydrogenase activity, and increased expression of pyruvate dehydrogenase kinase 4. Such a defect in IUGR mitochondria leads to a chronic reduction in the supply of ATP available from oxidative phosphorylation. Impaired ATP synthesis in muscle compromises energy-dependent GLUT4 recruitment to the cell surface, glucose transport, and glycogen synthesis, which contribute to insulin resistance and hyperglycemia of type 2 diabetes.