Objective-To develop a spatial epidemic model to simulate intraherd and interherd transmission of footand- mouth disease (FMD) virus. Sample Population-2,238 herds, representing beef, dairy, swine, goats, and sheep, and 5 sale yards located in Fresno, Kings, and Tulare counties of California. Procedure-Using Monte-Carlo simulations, a spatial stochastic epidemic simulation model was developed to identify new herds that would acquire FMD following random selection of an index herd and to assess progression of an epidemic after implementation of mandatory control strategies. Results-The model included species-specific transition periods for FMD infection, locations of herds, rates of direct and indirect contacts among herds, and probability distributions derived from expert opinions on probabilities of transmission by direct and indirect contact, as well as reduction in contact following implementation of restrictions on movements in designated infected areas and surveillance zones. Models of supplemental control programs included slaughter of all animals within a specified distance of infected herds, slaughter of only high-risk animals identified by use of a model simulation, and vaccination of all animals within a 5- to 50-km radius of infected herds.

Objective-To determine whether the nonsteroidal anti-inflammatory drugs (NSAIDs) carprofen, flunixin meglumine, and phenylbutazone have cyclooxygenase (COX)-independent effects that specifically inhibit activation of the proinflammatory transcription factor nuclear factor kappa B (NfκB). Study Population-Purified ovine COX-1 and -2 and cultures of RAW 264.7 murine macrophages. Procedure-The COX-1 and -2 inhibitory effects of the NSAIDs were tested in assays that used purified ovine COX-1 and -2. Prostaglandin production was analyzed by use of a radioimmunoassay. Inhibitory effects of these drugs on lipopolysaccharide (LPS)- induction of inducible nitric oxide synthase (iNOS) and LPS-stimulated translocation of NfκB were determined by use of RAW 264.7 murine macrophages. Results-Flunixin meglumine and phenylbutazone were selective inhibitors of COX-1. Carprofen and flunixin meglumine, but not phenylbutazone, inhibited LPS-induction of iNOS. Carprofen and, to a lesser degree, flunixin meglumine had inhibitory effects on NFκB activation. Conclusions and Clinical Relevance-The ability of drugs such as carprofen and flunixin meglumine to inhibit activation of NfκB-dependent genes such as iNOS, in addition to their effects on COX, suggests an additional mechanism for their anti-inflammatory effects and may explain the ability of flunixin meglumine to be an effective inhibitor of the effects of endotoxin in horses with endotoxemia.