Effects of decreased insulin-like growth factor-1 stimulation on hypoxia inducible factor 1-α protein synthesis and function during cutaneous repair in diabetic mice

Insulin-like growth factor-1 (Igf-1), a critical mediator of tissue repair, is significantly decreased in diabetic wounds. Furthermore, decreased levels of hypoxia-inducible factor 1-alpha (Hif-1alpha) and its target genes are also associated with impaired wound healing in diabetic mice. The aim of our study was to examine whether the reduced levels of Igf-1 are responsible for the reduction in Hif-1alpha protein synthesis and activity in diabetic wounds. We provide evidence that Igf-1 regulates Hif-1alpha protein synthesis and activity during wound repair. In addition, Igf-1 stimulated phosphytidylinositol 3-kinase activity in diabetic fibroblasts, which, in turn, increased activation of the translational regulatory protein, p70 S6 kinase. Moreover, improved healing of diabetic wounds by addition of recombinant IGF-1 protein was associated with an increase in Hif-1alpha protein synthesis and function in vivo.     

The effect of naloxone on the preoperative gastric volume and pH

The effect of 4 mg oral naloxone on preoperative gastric volume and pH of gastric aspirate was studied in a double-blind, randomized study. Twenty patients received 10 ml of naloxone (4 mg) mixed with 10 ml of orange juice, and 20 patients received 10 ml of isotonic saline mixed with 10 ml of orange juice, 2 h before surgery. Gastric content was obtained immediately after intubation of the trachea. No significant difference in gastric volume and pH of gastric aspirate was found between the two groups. It is concluded that naloxone does not affect gastric emptying and gastric acid secretion to a degree great enough to protect against aspiration of gastric contents into the lungs.     

Lung hydrolases in paraquat poisoning: early response of alkaline phosphatase

In order to evaluate the early response of the alveolar epithelium following lung injury, male Long-Evans adult rats (280-350 g) were treated with a single dose (30 mg/kg, ip) of the herbicide paraquat. No animal died during the 72 h that followed the acute administration of the herbicide. When compared to control, total lipid, phosphatidylcholine, and disaturated phosphatidylcholine contents of lung homogenates from the paraquat-treated rats were significantly reduced 48 h postdose (respectively 10, 24, and 37%). Comparatively, the total lung alkaline phosphatase activity was significantly reduced as early as 12 h postdose, and by 48 h the activity had decreased by approximately 50%. Although a significant decrease in total lung acid phosphatase activity was observed 24 and 48 h after the treatment, the effect was much less than with the alkaline phosphatase activity (15% versus 50%, respectively). The lysosomal beta-N-acetylglucosaminidase and the cytoplasmic lactate dehydrogenase activities were not affected by the herbicide treatment. A subcellular fractionation of the treated lungs showed that 48 h postdose, the total alkaline phosphatase activities associated with lamellar body and surfactant fractions were decreased respectively by 60% and 49%. Due to the intrinsic association of a strong alkaline phosphatase activity with the pulmonary surfactant system, these data suggest that the monitoring of the alkaline phosphatase activity in lung fractions could represent an early and sensitive indicator of toxicity to the alveolar epithelium, most probably to type II cells.