Efficacy of orally administered fluralaner in dogs against laboratory challenge with Haemaphysalis longicornis ticks.

BACKGROUND: Haemaphysalis longicornis ticks represent an ectoparasitic health threat to dogs. This study evaluated the immediate and persistent efficacy of orally administered fluralaner for control of this tick. METHODS: Twenty-four dogs were sorted into 4 groups based on their tick carrying capacity measured in a preliminary challenge. Two days before treatment, dogs were challenged with Haemaphysalis longicornis and then at the time of treatment dogs received with oral fluralaner at 10, 25 or 50 mg/kg respectively to 3 of the groups, while the remaining group was sham treated. Ticks were counted and categorized on all dogs 2 days after treatment (4 days after challenge). Tick challenges were repeated at 28, 56, 84 and 112 days following treatment with tick counts 48 hours following each challenge. Tick control efficacy was evaluated by comparing the mean (geometric) total live attached and dead engorged ticks on each fluralaner treated group with the sham treated dogs. RESULTS: Oral fluralaner is highly acaricidal for H. longicornis that feed on treated dogs. The mean efficacy rate in dogs treated with fluralaner at the commercial dose range of 25 to 50 mg/kg was greater than 90% at 114 days after treatment, whereas efficacy at this time in dogs treated at 10 mg/kg was 79%. CONCLUSIONS: Fluralaner administered orally to dogs within the commercial dose range at 25 to 50 mg/kg is effective for up to 114 days against laboratory challenge with H. longicornis ticks.

Dynamic changes in circulating leukocytes during the induction of equine laminitis with black walnut extract.

Administration of black walnut heartwood extract (BWHE) via nasogastric tube induces acute laminitis in horses. However, the processes responsible for the development of laminitis, including laminitis induced with BWHE, remain unclear. The results of recent studies indicate that administration of BWHE initiates an inflammatory response in the laminar tissues and that this response may be due to extravasation of activated leukocytes from the circulation. This study examines the effects of BWHE administration on the dynamics of circulating neutrophils and monocytes, and the capacity of blood leukocytes to produce radical oxygen species (ROS) over the time period from administration of BWHE to the development of lameness consistent with Obel grade I laminitis. Individual horses, free of pre-existing musculoskeletal disease, were administered either 6l of BWHE or an equal volume of water at time 0 (T=0). Blood samples were collected prior to dosing and at 1, 2, 3, 4, 6, 8, 10 and 12h after dosing, or until the onset of Obel grade I laminitis. For each sample, total leukocyte counts were determined followed by collection of buffy coats and removal of erythrocytes by hypotonic lysis. Leukocytes were either fixed for flow cytometric assessment of differential counts or maintained in culture to measure endogenous and phorbol ester-induced production of ROS. At each sample time, the number of cells recovered and the flow cytometric differential counts were compared with corresponding total leukocyte counts determined by the Clinical Pathology laboratory. Horses administered BWHE had a significant reduction in circulating leukocytes at 3-4 h relative to values for horses administered the same volume of water. Horses that developed Obel grade I laminitis had a significant reduction in circulating leukocytes when compared to values for horses administered BWHE that did not become lame. Flow cytometric analysis revealed a consistent decrease in the total number of monocytes obtained from horses that developed laminitis. In these same horses, the endogenous level of ROS production was significantly higher at T=0 than for horses that did not become lame. Furthermore, production of ROS by leukocytes from horses that developed laminitis increased significantly and coincided with the decrease in circulating leukocytes. Collectively, these findings support a role for systemic activation of leukocytes and induction of inflammation by BWHE as a factor in the early pathogenesis of acute laminitis. Because laminitis often develops as a sequel to diseases characterized by systemic inflammatory events, activation and emigration of neutrophils and monocytes may be important factors in the early pathogenesis of laminitis in clinical cases.

Genetic polymorphism of the nsp2 gene in North American type--porcine reproductive and respiratory syndrome virus.

We determined the complete nucleotide sequence of EDRD-1, a Japanese strain of the North American type-Porcine reproductive and respiratory syndrome virus (PRRSV), and identified a novel 117-base deletion and 108-base insertion previously reported in the nsp2 gene of the SP strain, which contains the largest genome among PRRSV strains. Based on genetic analysis of the partial nsp2 gene in 30 additional Japanese isolates and 50 strains from various countries, we classified North American-type PRRSVs into three nsp2-types, represented by EDRD-1, which contains the 117-base deletion and 108-base insertion; prototypic VR-2332, which does not contain the deletion and insertion; and SP, which contains only the 108-base insertion. The three nsp2-types were phylogenetically separated, suggesting that these structural changes only occurred at earlier stages of viral evolution. In the nsp2 genes, we identified an additional 19 deletions ranging from 3 to 378 bases and 2 insertions of 3 and 21 bases which were not common within each nsp2-type, suggesting that these changes occurred at later stages of viral evolution. In addition, our results suggest that the three nsp2-types can be rapidly differentiated by RT-PCR using their polymorphisms as natural tags.