ABSTRACT
We sought to determine the effectiveness of poloxamer 188 (P188) in protecting dystrophin-deficient, mdx skeletal muscle fiber membrane against exercise-induced breaches. mdx mice were treated with either P188 or placebo via intraperitoneal injections and run on a treadmill for 60-90 min. Membrane breakdown was quantified in cross-sections of rectus femoris muscle pretreated with Evans blue dye (in vivo). The mean % dye-penetrated muscle in the P188 and placebo groups was not significantly different in each of three trials. These results contrast with a recent report of P188 being highly effective in protecting the stretch- and dobutamine-stressed mdx heart muscle. The most likely explanations for the disparity are: (1) the exercise stress we used was beyond the protective range of P188, (2) P188 delivery and serum concentration were sub-optimal, or (3) the mdx skeletal myopathy and cardiomyopathy have fundamentally different responses to treatment.
Subject(s)
Cell Membrane Permeability/drug effects , Muscle Fibers, Skeletal/drug effects , Muscle, Skeletal/drug effects , Muscular Dystrophy, Duchenne/drug therapy , Poloxamer/pharmacology , Sarcolemma/drug effects , Animals , Cardiomyopathies/drug therapy , Cardiomyopathies/metabolism , Cardiomyopathies/physiopathology , Cell Membrane Permeability/physiology , Coloring Agents , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Administration Routes , Exercise Tolerance/drug effects , Exercise Tolerance/physiology , Female , Injections, Intraperitoneal , Male , Mice , Mice, Inbred C57BL , Mice, Inbred mdx , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/pathology , Muscle, Skeletal/metabolism , Muscle, Skeletal/physiopathology , Muscular Dystrophy, Duchenne/metabolism , Muscular Dystrophy, Duchenne/physiopathology , Physical Conditioning, Animal/physiology , Poloxamer/therapeutic use , Sarcolemma/metabolism , Surface-Active Agents/pharmacology , Surface-Active Agents/therapeutic use , Treatment FailureABSTRACT
The airborne fungal spore concentration measured with air samplers during specific time intervals does not always adequately represent the maximum spore concentration levels, because of the sporadic nature of spore release. Hence, a reliable method is needed to directly assess the indoor fungal sources with respect to their spore aerosolization potential. In this study, the newly developed fungal spore source strength tester (FSSST), which aerosolizes spores from growth surfaces and samples the airborne fungi into a bioaerosol sampler, was evaluated in the laboratory. The FSSST's operational flow rates of 30 and 12.5 l/min were tested. The fungal spores released from moldy surfaces were measured with an optical particle counter. Simultaneously, the spores were collected by a bioaerosol sampler: either with a 37-mm filter cassette or with the BioSampler. Three material types, ceiling tile, gypsum board and plastic sheet coated with agar, were tested after they were inoculated with the fungus Aspergillus versicolor. In addition, gypsum board naturally contaminated with various fungi (obtained from a mold-problem home) was tested in the laboratory using the FSSST. In all three laboratory-inoculated materials, the release rate of A. versicolor was found to be higher when the FSSST operated at 30 l/min than at 12.5 l/min. Nevertheless, even at 12.5 l/min the number of spores aerosolized from the source during 10 min was found sufficient to reflect the highest level of release that may occur in indoor environments. At 12.5 l/min, the release rate of A. versicolor during the first 10-min period was (23.9 +/- 17.7)x10(4) cm(-2) for ceiling tile, (1.3 +/- 0.3)x10(4) cm(-2) for gypsum board and (0.13 +/- 0.08)x10(4) cm(-2) for agar surface (based on the samples collected with the BioSampler). The spore release rate was higher during the first 10 min than during the second 10 min of the FSSST application. It was observed that the particles aerosolized from the A. versicolor culture included spore aggregates and single spores, as well as mycelial fragments. Overall, 0.6 +/- 0.3% of spores detected on 1 cm2 of ceiling tile inoculated with A. versicolor were aerosolized during the 10-min source testing. The respective number was 9.2 +/- 1.0% for the laboratory-inoculated gypsum board, 0.002 +/- 0.001% for the laboratory-inoculated plastic covered with agar and 1.8 +/- 0.2% for naturally contaminated gypsum board. Our data suggest that the FSSST provides very favorable conditions for the spore aerosolization and thus can be used in the field to assess the maximum potential spore release from a fungal source.
