Targeting of plasminogen activator inhibitor 1 improves fibrinolytic therapy for tetracycline-induced pleural injury in rabbits.

Endogenous active plasminogen activator inhibitor 1 (PAI-1) was targeted in vivo with monoclonal antibodies (mAbs) that redirect its reaction with proteinases to the substrate branch. mAbs were used as an adjunct to prourokinase (single-chain [sc] urokinase [uPA]) intrapleural fibrinolytic therapy (IPFT) of tetracycline-induced pleural injury in rabbits. Outcomes of scuPA IPFT (0.25 or 0.0625 mg/kg) with 0.5 mg/kg of mouse IgG or mAbs (MA-33H1F7 and MA-8H9D4) were assessed at 24 hours. Pleural fluid (PF) was collected at 0, 10, 20, and 40 minutes and 24 hours after IPFT and analyzed for plasminogen activating (PA), uPA, fibrinolytic activities, levels of total plasmin/plasminogen, α-macroglobulin (αM), mAbs/IgG antigens, free active uPA, and αM/uPA complexes. Anti-PAI-1 mAbs, but not mouse IgG, delivered with an eightfold reduction in the minimal effective dose of scuPA (from 0.5 to 0.0625 mg/kg), improved the outcome of IPFT (P < 0.05). mAbs and IgG were detectable in PFs at 24 hours. Compared with identical doses of scuPA alone or with IgG, treatment with scuPA and anti-PAI-1 mAbs generated higher PF uPA amidolytic and PA activities, faster formation of αM/uPA complexes, and slower uPA inactivation. However, PAI-1 targeting did not significantly affect intrapleural fibrinolytic activity or levels of total plasmin/plasminogen and αM antigens. Targeting PAI-1 did not induce bleeding, and rendered otherwise ineffective doses of scuPA able to improve outcomes in tetracycline-induced pleural injury. PAI-1-neutralizing mAbs improved IPFT by increasing the durability of intrapleural PA activity. These results suggest a novel, well-tolerated IPFT strategy that is tractable for clinical development.

Compensation scheme for complementary and alternative medicine use in asbestos-related diseases in New South Wales, Australia.

WHAT IS KNOWN AND OBJECTIVE: Asbestos use has resulted in a high global incidence rate of asbestos-related diseases (ARDs). These diseases require high costs of compensation and medical expense, although definite cures have yet to be found. Complementary and alternative medicine (CAM) has been used as a means to attenuate symptoms of ARDs. Our objective is to describe the compensation scheme for CAM use for a population with ARDs in New South Wales (NSW), Australia. COMMENT: Expenses of CAM have conditionally been compensated by the workers compensation dust-diseases board (DDB) to a population with ARDs. The DDB approves patients` claim for the use of CAM if it is justifiable and related to compensable ARDs. To obtain the DDB`s approval for the CAM cost, a written recommendation letter by the treating medical doctors is required that justifies the use of CAM and that this option does not pose any adverse effects on the compensated patients. WHAT IS NEW AND CONCLUSION: The use of CAM in a subject with ARDs does not have significant benefits of overall survival but does somewhat improve quality of life. However, awareness of the provisions of the compensation scheme for CAM use in a population with ARDs should be carefully informed and also emphasized any side effects on progress of ARDs.

Background documentation of evaluation of occupational exposure to airborne asbestos.

This review presents background information and literature documentation to supplement the "Recommended Procedures for Sampling and Counting Asbestos Fibers: Procedures for the Evaluation of Occupational Exposure to Airborne Asbestos" prepared by the joint ACGIH-AIHA Aerosol Hazards Evaluation Committee. It reviews the nature of the inhalation hazard associated with asbesots fibers, the sampling and analytic methods which have been used, and a rationale for the selection of the membrane filter sampling-optical phase microscope identification and assay methodology which is recommended.