The antibiotic polymyxin B sulfate is a cationic polypeptide with a unique cyclical configuration and distinct cationic characteristics. In this investigation, polymyxin B was evaluated to determine its ability to prevent synthesis of lactic acid and tumor necrosis factor-alpha (TNF-alpha) by lipopolysaccharide-stimulated strain RAW 2647 macrophage-like cell populations. In this context, gradient concentrations of polymyxin B were formulated in the presence of fixed concentrations of lipopolysaccharide fractions from Escherichia coli (B4:0111), E. coli (J5), Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella minnesota, and S. typhimurium (Re). Quantitation of TNF-alpha was established by the application of a tissue culture-based biological assay system, using the WEHI 164 clone 13 indicator cell line. Investigations also included evaluation of the ability of gradient concentrations of lipopolysaccharide fractions from E. coli (B4:0111), E. coli (J5), K. pneumoniae, P. aeruginosa, S. minnesota, and S. typhimurium (Re) to form a complex with polymyxin B. This was established through application of high-performance thin-layer chromatography techniques. On the basis of the known molecular characteristics of lipopolysaccharide, its lipid A-core subfractions, and polymyxin B, these results imply that cytoprotective properties of polymyxin B are attributable to direct interaction and subsequent complex formation. More specifically, the mechanism by which polymyxin B exerts affinity for lipopolysaccharide fractions is proposed to occur through attractive ionic interactions established between the cationic diaminobutyric acid residues of polymyxin B and the mono- or diphosphate group(s) of the lipid A-core moiety. It is highly probable that this molecular phenomenon is accompanied by hydrophobic interactions established between the terminal methyloctanoyl or methylheptanoyl groups of polymyxin B and the saturated carbon chains of the lipid A-core subfraction of lipopolysaccharide fractions.

Studies were undertaken to determine the efficacy of milbemycin oxime against the enteric adult stages of Trichinella spiralis and of albendazole against the muscle stage larvae in experimentally infected dogs and cats. Specific-pathogen-free Beagle pups (n = 6) and domestic shorthair kittens (n = 6) were inoculated with 7,500 first-stage larvae of Trichinella spiralis. Physical examination (including collection of blood and fecal samples) was performed weekly. During the first week after inoculation, all animals had mild gastrointestinal tract disturbances, but stages of T. spiralis were not observed in the feces. Beginning on postinoculation day (PID) 10, 3 pups and 3 kittens were treated with milbemycin oxime (1.25 mg/kg of body weight, PO, q 12 h) for 10 days. Muscle biopsy specimens were taken from dogs and cats on PID 26 and 29, respectively. Mean numbers of larvae per gram of muscle were 30.3 in the control and 37.7 in the treated dogs. Mean numbers of larvae per gram of muscle in the control and treated cats were 318.7 and 89.3, respectively. Two dogs and 2 cats were removed from the study at that time. The remaining animals, 2 each of the control and milbemycin oxime-treated animals, were given albendazole (50 mg/kg, PO, q 12 h) for 7 days starting at PID 31 and 34 in dogs and cats, respectively. Muscle biopsy specimens were again taken at PID 46 and 49, for dogs and cats, respectively; mean numbers of larvae recovered from muscle were 0.6 for dogs and 13.5 for cats.