Background
Pharmacokinetics of amikacin administered IV to neonatal foals are described, but little data are available regarding the plasma concentrations contributed by concurrent intra‐articular ...(IA) administration.
Hypothesis/Objectives
Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens.
Animals
Eight healthy neonatal foals.
Methods
Foals received 3 amikacin treatment protocols: (1) IV‐only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA‐only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 μg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility.
Results
Foal age was a significant variable. The IV‐only protocol met or exceeded the 30‐minute plasma concentrations considered therapeutic (mean μg/mL 95% confidence interval, CI) in 7‐ to 9‐day‐old (54.0 52.2‐56.9), 14‐ to 16‐day‐old (58.1 55.2‐61.0), and 21‐ to 23‐day‐old (66.6 63.7‐69.6) foals. Concurrent IV and IA protocol did not reach the 30‐minute concentration considered therapeutic in 7‐ to 9‐day‐old foals (46.5 43.6‐49.4) but did in 14‐ to 16‐day‐old (62.9 60.0‐65.8) and 21‐to 23‐day‐old (62.6 59.7‐65.6) foals.
Conclusions and Clinical Importance
Concurrent IV and IA administration of amikacin produces 30‐minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin.
Background
Three flaviviruses (equine pegivirus EPgV; Theiler's disease–associated virus TDAV; non‐primate hepacivirus NPHV) and equine parvovirus (EqPV‐H) are present in equine blood products; the ...TDAV, NPHV, and EqPV‐H have been suggested as potential causes of serum hepatitis.
Objective
To determine the prevalence of these viruses in horses with equine serum hepatitis.
Animals
Eighteen horses diagnosed with serum hepatitis, enrolled from US referral hospitals.
Methods
In the prospective case study, liver, serum, or both samples were tested for EPgV, TDAV, NPHV, and EqPV‐H by PCR.
Results
Both liver tissue and serum were tested for 6 cases, serum only for 8 cases, and liver only for 4 cases. Twelve horses received tetanus antitoxin (TAT) 4‐12.7 weeks (median = 8 weeks), 3 horses received commercial equine plasma 6‐8.6 weeks, and 3 horses received allogenic stem cells 6.4‐7.6 weeks before the onset of hepatic failure. All samples were TDAV negative. Two of 14 serum samples were NPHV‐positive. Six of 14 serum samples were EPgV‐positive. All liver samples were NPHV‐negative and EPgV‐negative. EqPV‐H was detected in the serum (N = 8), liver (N = 4), or both samples (N = 6) of all 18 cases. The TAT of the same lot number was available for virologic testing in 10 of 12 TAT‐associated cases, and all 10 samples were EqPV‐H positive.
Conclusions and Clinical Importance
We demonstrated EqPV‐H in 18 consecutive cases of serum hepatitis. EPgV, TDAV, and NPHV were not consistently present. This information should encourage blood product manufacturers to test for EqPV‐H and eliminate EqPV‐H–infected horses from their donor herds.
Equine metabolic syndrome is characterized by obesity and regional adiposity coupled with evidence of recurrent laminitis. Although inflammation has been well characterized in several experimental ...models of acute laminitis, the inflammatory events associated with endocrinopathic laminitis are not well documented. The aim of this study was to characterize selected markers of inflammation in horses with clinical evidence of equine metabolic syndrome (EMS). Neutrophil phagocytosis and oxidative burst, as well as endogenous and stimulated cytokine expression were evaluated. A marked increase in neutrophil reactive oxygen species production upon phagocytosis was observed in horses with EMS that was strongly correlated to the blood insulin concentration. Increased oxidative burst activity of neutrophils in hyperinsulinemic horses may predispose horses with metabolic syndrome to laminitis. In contrast, peripheral blood cells of obese hyperinsulinemic horses showed decreased endogenous proinflammatory cytokine gene expression (IL-1 and IL-6) and similar cytokine response following immune stimulation compared to that of control horses. This may suggest that, unlike in people, cytokine-mediated inflammation does not increase in direct response to obesity or insulin resistance in horses. This species-specific disparity may explain the difference in clinical outcomes observed in obese horses compared to obese people.
1. Population structure, distribution, abundance and dispersal arguably underpin the entire field of animal ecology, with consequences for regional species persistence, and provision of ecosystem ...services. Divergent migration behaviours among individuals or among populations are an important aspect of the ecology of highly mobile animals, allowing populations to exploit spatially or temporally distributed food and space resources. 2. This study investigated the spatial ecology of lake sturgeon (Acipenser fulvescens) within the barrier free Huron-Erie Corridor (HEC), which connects Lake Huron and Lake Erie of the North American Laurentian Great Lakes. 3. Over 6 years (2011-2016), movements of 268 lake sturgeon in the HEC were continuously monitored across the Great Lakes using acoustic telemetry (10 years battery life acoustic transmitters). Five distinct migration behaviours were identified with hierarchical cluster analysis, based on the phenology and duration of river and lake use. 4. Lake sturgeon in the HEC were found to contain a high level of intraspecific divergent migration, including partial migration with the existence of residents. Specific behaviours included year-round river residency and multiple lake-migrant behaviours that involved movements between lakes and rivers. Over 85% of individuals were assigned to migration behaviours as movements were consistently repeated over the study, which suggested migration behaviours were consistent and persistent in lake sturgeon. Differential use of specific rivers or lakes by acoustic-tagged lake sturgeon further subdivided individuals into 14 "contingents" (spatiotemporally segregated subgroups). 5. Contingents associated with one river (Detroit or St. Clair) were rarely detected in the other river, which confirmed that lake sturgeon in the Detroit and St. Clair represent two semi-independent populations that could require separate management consideration for their conservation. The distribution of migration behaviours did not vary between populations, sexes, body size or among release locations, which indicated that intrapopulation variability in migratory behaviour is a general feature of the spatial ecology of lake sturgeon in unfragmented landscapes.
Channelization for navigation and flood control has altered the hydrology and bathymetry of many large rivers with unknown consequences for fish species that undergo riverine migrations. In this ...study, we investigated whether altered flow distributions and bathymetry associated with channelization attracted migrating Lake Sturgeon (Acipenser fulvescens) into commercial navigation channels, potentially increasing their exposure to ship strikes. To address this question, we quantified and compared Lake Sturgeon selection for navigation channels vs. alternative pathways in two multi-channel rivers differentially affected by channelization, but free of barriers to sturgeon movement. Acoustic telemetry was used to quantify Lake Sturgeon movements. Under the assumption that Lake Sturgeon navigate by following primary flow paths, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River were expected to choose navigation channels over alternative pathways and to exhibit greater selection for navigation channels than conspecifics in the less-channelized lower St. Clair River. Consistent with these predictions, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River selected the higher-flow and deeper navigation channels over alternative migration pathways, whereas in the less-channelized lower St. Clair River, individuals primarily used pathways alternative to navigation channels. Lake Sturgeon selection for navigation channels as migratory pathways also was significantly higher in the more-channelized lower Detroit River than in the less-channelized lower St. Clair River. We speculated that use of navigation channels over alternative pathways would increase the spatial overlap of commercial vessels and migrating Lake Sturgeon, potentially enhancing their vulnerability to ship strikes. Results of our study thus demonstrated an association between channelization and the path use of migrating Lake Sturgeon that could prove important for predicting sturgeon-vessel interactions in navigable rivers as well as for understanding how fish interact with their habitat in landscapes altered by human activity.
Because microstructure plays an important role in the mechanical properties of structural materials, developing the capability to quantify microstructures rapidly is important to enabling ...high‐throughput screening of structural materials. Electron backscatter diffraction (EBSD) is a common method for studying microstructures and extracting information such as grain size distributions (GSDs), but is not particularly fast and thus could be a bottleneck in high‐throughput systems. One approach to accelerating EBSD is to reduce the number of points that must be scanned. In this work, we describe an iterative method for reducing the number of scan points needed to measure GSDs using incremental low‐discrepancy sampling, including on‐the‐fly grain size calculations and a convergence test for the resulting GSD based on the Kolmogorov–Smirnov test. We demonstrate this method on five real EBSD maps collected from magnesium AZ31B specimens and compare the effectiveness of sampling according to two different low discrepancy sequences, the Sobol and R2 sequences, and random sampling. We find that R2 sampling is able to produce GSDs that are statistically very similar to the GSDs of the full density grids using, on average, only 52% of the total scan points. For EBSD maps that contained monodisperse GSDs and over 1000 grains, R2 sampling only required an average of 39% of the total EBSD points.
Cannabidiol (CBD) products have gained popularity among horse owners despite limited evidence regarding pharmacokinetics. The purpose of this study was to describe the pharmacokinetic profile of ...multiple doses of an orally administered cannabidiol product formulated specifically for horses. A randomized 2-way crossover design was used. Seven horses received 0.35 or 2.0 mg/kg CBD per os every 24 hours for 7 total doses, separated by a 2-week washout. Plasma CBD and delta-9-tetrahydrocannabinol (THC) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) daily through day 10, then on day 14 after beginning CBD administration. On the final day of CBD administration, plasma CBD and THC were quantified at multiple times. After administration of 0.35 mg/kg of CBD, the Cmax of CBD was 6.6 ± 2.1 ng/mL while Tmax was 1.8 ± 1.2 hour, whereas the Cmax for THC was 0.7 ± 0.6 ng/mL with a Tmax of 2.5 ± 1 hour. After administration of 2.0 mg/kg of CBD, the Cmax of CBD was 51 ± 14 ng/mL with a mean Tmax of 2.4 ± 1.1 hour and terminal phase half-life of 10.4 ± 6 hour, whereas the Cmax of THC was 7.5 ± 2.2 ng/mL with a Tmax of 2.9 ± 1.1 hour. Oral administration of a cannabidiol product at 0.35 mg/kg or 2.0 mg/kg once daily for 7 days was well-tolerated. Based on plasma CBD levels obtained, dose escalation trials in the horse evaluating clinical efficacy at higher mg/kg dose rates are indicated.
•Once daily dosing of CBD at 0.35 and 2.0 mg/kg in the horse was well-tolerated but may result in plasma levels insufficient to provide clinical results.•CBD appeared in plasma rapidly after oral administration and showed an initial rapid decline followed by a more prolonged terminal elimination phase half-life.•Measurable THC levels are detectable in plasma with administration of this CBD product, highlighting the need to educate veterinarians and horse owners administering cannabidiol to competitive horses.
Understanding the spatial ecology of sturgeon (Acipenseridae) has proven to be a challenge due to the life history characteristics of these fish, especially their long life span, intermittent ...spawning, and long‐distance migrations. Within the Huron‐Erie Corridor (HEC) of the Laurentian Great Lakes, habitat use of 247 lake sturgeon (Acipenser fulvescens) was monitored over a three‐year period (2015–2017) with acoustic transmitters. Extensive spatial coverage of receivers throughout the St. Clair River, Lake St. Clair, and Detroit River between Lake Huron and Lake Erie (~150 km) allowed for continuous monitoring of the movements of acoustic‐tagged individuals. Sequence analysis of individual detection histories was used to describe lake sturgeon habitat use and to determine (1) whether distinct habitat‐use patterns occurred within the HEC; (2) whether the range of habitats occupied varied across seasons among sturgeon grouped by common patterns; and (3) whether variation identified was related to tagging sites in the two rivers or sex. Lake sturgeon were active throughout the HEC, but five distinct habitat‐use patterns were identified. River residents were not broadly distributed across entire rivers, but rather associated with particular segments (middle Detroit River, St. Clair River delta). Variations in habitat‐use sequences were in part related to three river tagging sites, but not sex, and did not produce groups with sequences that reflected all five habitat‐use patterns derived from cluster analysis. Lake sturgeon distribution was reduced to fewer habitat segments during winter and expanded to the maximum extent during the spring and summer. Conservation planning that incorporates behavioral diversity of habitat use is relatively rare due to a lack of observations on movements of individuals at biologically relevant spatial and temporal scales, but using telemetry and sequence analysis methods may promote the success of conservation and restoration efforts.
Objective
To determine the effect of volume of amikacin perfusate for intravenous regional limb perfusion (IVRLP) via the cephalic vein in standing, sedated horses on (1) amikacin concentrations in ...the synovial fluid of the radiocarpal joint (RCJ) and distal interphalangeal joint (DIPJ) and, (2) amikacin concentration in the systemic circulation, and (3) regional intravenous pressure.
Study Design
Randomized cross‐over design.
Animals
Six adult horses.
Methods
Each horse received IVRLP using 4 perfusate volumes (10, 30, 60 & 120 ml) in random order, after a minimum of 1 week washout. After application of a pneumatic tourniquet, IVRLP with 1 g of amikacin in 0.9% NaCl was performed. Synovial fluid from the RCJ and DIPJ, and systemic and regional venous blood were sampled, and regional blood pressure was measured, immediately before perfusion (time 0), and 15 and 30 minutes after perfusion but before tourniquet release.
Results
No difference was observed in the mean amikacin concentration of synovial fluid for the 4 perfusate volumes (P>.09). For all volumes, mean amikacin concentration for DIPJ synovial fluid was higher than for RCJ (P<.0001). The mean amikacin concentration in DIPJ synovial fluid was therapeutic for resistant pathogens using the 10, 60, and 120 mL volumes but the mean amikacin concentration for RCJ synovial fluid was not therapeutic for resistant pathogens with any perfusate volume. All volumes resulted in an immediate increase in mean regional intravascular pressure after perfusion (P<.0001) but was not different across the 4 perfusate volumes.
Conclusion
Cephalic IVRLP of 1 g of amikacin diluted to a volume of 10–120 mL with 0.9% NaCl will achieve amikacin concentrations therapeutic for resistant pathogens in the synovial fluid from the DIPJ. Concentrations below therapeutic levels for resistant pathogens are reached in the synovial fluid from the RCJ.
Objective
To determine the influence of a dual tourniquet technique and limb exsanguination on amikacin concentrations in the synovial fluid of the radiocarpal joint (RCJ) and distal interphalangeal ...joint (DIPJ) after low volume, cephalic intravenous regional limb perfusion (IVRLP).
Study design
Randomized cross‐over design.
Animals
Six healthy adult horses.
Methods
One gram of amikacin in 6 mL of 0.9% NaCl was infused via cephalic IVRLP in 6 standing, sedated horses using 4 techniques: proximal pneumatic tourniquet (P), proximal pneumatic tourniquet with exsanguination (PE), proximal pneumatic and distal Esmarch tourniquet (PD), and proximal pneumatic with distal Esmarch tourniquet and exsanguination (PDE). Amikacin concentrations were measured in RCJ and DIPJ synovial fluid samples, collected just before perfusion (time 0), and at 15 and 30 minutes (before tourniquet release) after perfusion.
Results
Synovial fluid amikacin concentrations achieved in the RCJ were higher with techniques PD and PDE than those achieved with techniques P and PE 15 and 30 minutes after perfusion (P < .0001). Synovial fluid amikacin concentrations in the DIPJ were higher with techniques P and PE than those achieved with techniques PD and PDE at 15 minutes (P = .0002) and were higher than technique PDE at 30 minutes after perfusion (P < .0001).
Conclusion
Low volume (10 mL) cephalic IVRLP should be combined with the placement of 2 tourniquets (proximal and distal to the carpus) to achieve therapeutic amikacin concentrations in the RCJ. Exsanguination prior to low volume IVRLP does not alter synovial fluid amikacin concentrations.
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