Estimation of foot-and-mouth disease windborne transmission risk from USA beef feedlots.

Windborne spread of foot-and-mouth disease (FMD) requires specific epidemiological and meteorological conditions, thus modeling the risk of windborne spread involves integrating epidemiological and meteorological models. The objective of this study was to investigate the potential risk of windborne spread of FMD from an infected US feedlot using an integrated modeling approach, and to identify factors that determine this risk. To address this objective, we integrated a within-herd epidemiological model and an advanced atmospheric dispersion model, and calculated infection risk dependent on exposed herd size. A previously developed epidemiological model was used to simulate the spread of FMD through a typical U.S. feedlot, while the National Oceanic and Atmospheric Administration's (NOAA) HYSPLIT atmospheric dispersion model, which has been validated for FMD modeling, was used to model virus dispersion. Infection risk for exposed herds was calculated as a binomial probability accounting for dose and exposed herd size. We modeled risk of windborne spread from a typical 4000 head feedlot in the U.S. state of Iowa (IA), and a typical 48,000 head feedlot in the U.S. state of Kansas (KS) during winter and summer seasons. The risk of windborne spread of FMD varied based on weather/season conditions, estimated average viral shedding rate per head, size of infected herd, and size of exposed herd. In the baseline Kansas scenario (KS/103/W), the median of the maximum daily risk of infecting a 1000-head exposed herd ranged from 58.16 % at 1 km to 0.78 % at 10 km (Table 4). In the baseline Iowa scenario (IA/103/W), the median of the maximum daily risk of infecting a 1000-head exposed herd ranged from 21.78 % at 1 km to 0.05 % at 10 km (Table 4). The minimum control area recommended by the United States Department of Agriculture (USDA) in an FMD outbreak is 10 km from the infected premise. Our results indicate that significant risk of windborne spread may extend beyond 10 km in certain situations. This is particularly a concern in areas where there are large feedlots in relatively close proximity, such as in southwestern Kansas. Our model may be useful as a research tool in the absence of an outbreak and may help direct surveillance and response efforts in the event of an outbreak.

The role of Veterinary Services in areas of conflict.

Armed conflict significantly impacts livestock production, animal health, public health, and the delivery of Veterinary Services by limiting resources, eroding border control, disrupting land use, impairing disease surveillance, and reducing food safety and quality. Those seeking to build capacity in animal health in areas of conflict should focus on strengthening resilience in animal production systems and animal health infrastructure to minimise the devastating effects of conflict. Methods for reconstructing Veterinary Service systems should be tailored to each country's specific needs. These can be determined through participatory assessment, with a focus on building sustainable relationships among all stakeholders. Although it is tempting for animal health professionals to focus primarily on improving animal health on individual farms or targeting specific diseases, attention should be centred on entire systems and on developing sustainable agricultural improvements that will enhance livelihoods on a national scale. Aiding economic growth can also help to lower the probability of future conflict.

Les conflits armés ont d'importantes répercussions sur l'élevage, la santé animale, la santé publique et les prestations des Services vétérinaires, car ils limitent les ressources, mettent à mal les contrôles aux frontières, perturbent l'utilisation des terres, nuisent à la surveillance des maladies et réduisent la sécurité sanitaire et la qualité des aliments. Les acteurs cherchant à renforcer les capacités en santé animale dans les zones de conflit devraient se centrer sur la consolidation de la résilience des systèmes de production animale et des infrastructures de santé animale afin de réduire au minimum les effets dévastateurs du conflit. Il convient d'adapter les méthodes de reconstruction des Services vétérinaires aux besoins spécifiques de chaque pays. Ceux-ci peuvent être estimés à partir d'évaluations participatives, qui mettent l'accent sur l'édification de relations durables entre tous les acteurs concernés. S'il peut être tentant pour les professionnels de la santé animale de s'attacher en premier lieu à l'amélioration de la santé animale dans des exploitations individuelles ou de cibler certaines maladies particulières, il faudrait plutôt centrer l'attention sur les systèmes dans leur ensemble et sur la mise sur pied d'améliorations agricoles durables qui finiront par renforcer les moyens de subsistance à l'échelle nationale. Les mesures favorisant la croissance économique peuvent également contribuer à réduire la probabilité d'un futur conflit.

Los conflictos armados inciden sustancialmente en la producción ganadera, la sanidad animal, la salud pública y la prestación de servicios veterinarios porque disminuyen los recursos disponibles, erosionan los controles de fronteras, desorganizan los usos del suelo, dificultan la vigilancia de enfermedades y merman los niveles de inocuidad y calidad de los alimentos. Quienes traten de potenciar los medios de acción zoosanitaria en zonas de conflicto deberían centrarse en conferir más resiliencia a los sistemas de producción animal y las infraestructuras zoosanitarias con el fin de reducir al mínimo los devastadores efectos de los conflictos. Los métodos para reconstruir los sistemas de prestación de servicios veterinarios deben estar adaptados a las necesidades específicas de cada país, necesidades que se pueden determinar con procesos de evaluación participativa, procurando especialmente forjar relaciones sostenibles entre todas las partes interesadas. Aunque para los profesionales de la sanidad animal resulte tentador centrarse primordialmente en la mejora de las condiciones zoosanitarias en las explotaciones o combatir selectivamente determinadas enfermedades, lo conveniente es prestar atención a los sistemas considerados en su conjunto e introducir en el mundo agropecuario mejoras sostenibles que potencien los medios de vida de la población de todo el país. El hecho de apuntalar el crecimiento económico también puede ser útil para reducir las probabilidades de conflicto en el futuro.

The role of glutathione in the neurotoxicity of artemisinin derivatives in vitro.

The role of antioxidants in the neurotoxicity of the antimalarial endoperoxides artemether and dihydroartemisinin was studied in vitro by quantitative image analysis of neurite outgrowth in the neuroblastoma cell line NB2a. Intracellular glutathione concentrations were measured by high performance liquid chromatography with fluorescence detection. Both dihydroartemisinin (1 microM) and a combination of artemether (0.3 microM) plus haemin (2 microM) significantly inhibited neurite outgrowth from differentiating NB2a cells to 11.5 +/- 11.0% (SD) and 19.6 +/- 15.2% of controls, respectively. The inhibition by artemether/haemin was prevented by the antioxidants superoxide dismutase (109.7 +/- 47.8% of control), catalase (107.0 +/- 29.3%) glutathione (123.8 +/- 12.4%), L-cysteine (88.0 +/- 6.3%), N-acetyl-L-cysteine (107.8 +/- 14.9%), and ascorbic acid (104.3 +/- 12.7%). Dihydroartemisinin-induced neurotoxicity was completely or partially prevented by L-cysteine (99.5 +/- 17.7% of control), glutathione (57.9 +/- 23.4% of control), and N-acetyl-L-cysteine (57.3 +/- 9.5%), but was not prevented by superoxide dismutase, catalase, or ascorbic acid. Buthionine sulphoximine, an inhibitor of gamma-glutamylcysteine synthetase, significantly increased the neurotoxic effect of non-toxic concentrations of artemether/haemin (0.1 microM/2 microM) and dihydroartemisinin (0.2 microM), suggesting that endogenous glutathione participates in the prevention of the neurotoxicity of artemether/haemin and dihydroartemisinin. Artemether/haemin completely depleted intracellular glutathione levels, whereas dihydroartemisinin had no effect. We conclude that although glutathione status is an important determinant in the neurotoxicity of endoperoxides, depletion of glutathione is not a prerequisite for their toxicity. This is consistent with their mechanisms of toxicity being free radical-mediated damage to redox-sensitive proteins essential for neurite outgrowth, or alteration of a redox-sensitive signalling system which regulates neurite outgrowth.

Hepatocellular response to chemical stress in CD-1 mice: induction of early genes and gamma-glutamylcysteine synthetase.

Exposure of cells to toxic chemical species can result in reduced glutathione (GSH) depletion, generation of free radicals, and/or binding to critical cell determinants. Chemical stress is usually followed by a concerted cellular response aimed at restoring homeostasis, although the precise initial stimulus for the response is unclear. We have focused on one component of this stress response, the up-regulation of gamma-glutamylcysteine synthetase (gamma-GCS) and the preceding molecular events involved in its regulation in an in vivo mouse model. Male CD-1 mice received buthionine sulphoximine (BSO; 7.2 mmol/kg), diethyl maleate (DEM; 4.2 mmol/kg), paracetamol (APAP; 3.5 and 1.0 mmol/kg), or carbon tetrachloride (CCl(4); 1.0 and 0.2 mmol/kg). Biochemical (serum transaminase and hepatic GSH levels) and molecular (c-jun and c-fos messenger RNA [mRNA] levels and activator protein 1 [AP-1] DNA binding activity) parameters were measured, as well as the consequent effects on gamma-GCS levels and activity. All compounds produced GSH depletion, but only the higher doses of APAP and CCl(4) caused liver damage. DEM, APAP, and CCl(4) increased c-jun and c-fos mRNA levels, together with an increase in AP-1 binding; BSO failed to induce AP-1 despite an increase in c-fos. Interestingly, the effects on gamma-GCS varied markedly according to the compound: BSO and DEM increased gamma-GCS enzyme activity, although only DEM, but not BSO, resulted in an increase in gamma-GCS(h) mRNA and protein. In contrast, APAP and CCl(4) both increased gamma-GCS(h) mRNA and protein; however, there was a marked dose-dependent decrease in gamma-GCS activity. These data indicate that the effect of chemical stress on the liver is compound specific and is not merely dependent on depletion of GSH.