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.     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

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.     

Serologic investigation of fatal hemolytic anemia associated with a multiple drug history and Rh-like autoantibody

A patient who expired during an episode of gross intravascular hemolysis had a complex medical history, including renal disease, Coombs positive anemia of unclear etiology, recent transfusion, and cholecystectomy. Drug history included 21 different medications, including penicillin, acetaminophen, procainamide, furosemide, sulindac, and tolmetin, all of which have been associated with a positive direct antiglobulin test or drug-induced hemolytic anemia. The patient had a history of recent use of three chemically similar nonsteroidal anti-inflammatory drugs: tolmetin (Tolectin), sulindac (Clinoril), and ketorolac (Toradol). Only tolmetin and furosemide (Lasix) antibodies were demonstrable in the patient's serum at the time of her final admission. The patient's serum at final admission contained panagglutinating IgG and IgM antibody with a titer of 1:80 using a pool of R1R1 and R2R2 screening cells. When tolmetin was added to the test system, the titer increased to 1:2,560. The direct antiglobulin test was 3+ (IgG and C3d,b). Eluates contained an Rh-like antibody compatible only with Rh deletion cells, and anti-tolmetin antibodies detected when the drug was added to the eluate in the presence of Rh deletion cells. Allogeneic adsorbed sera contained anti-tolmetin antibodies with a titer of 1:10 and a weakly reactive IgM antibody to furosemide. Antibodies to tolmetin and furosemide were apparent only when the drugs were added to sera or eluates, not with drug-coated cells. Because of the patient's complex medical history, it was not possible to attribute the fatal autoimmune hemolytic anemia solely to drug antibody.