Effect of storage duration on carprofen concentration measurements in dog plasma.

BACKGROUND: Storage of samples may be necessary prior to testing drug levels in certain study designs; however, the effect of storage duration on measured drug levels is not known for all drugs. OBJECTIVES: The objective of this study was to evaluate the stability of carprofen in canine plasma when stored at -80°C for 6 months. METHODS: Six healthy dogs were enrolled (1-10 years old, 17-35 kg) and received compounded carprofen at 2.2 mg/kg orally every 12 h for 2 days. On the third day, blood was collected immediately before the morning dose (trough), then 1 and 6 h after the dose (sampling timepoint). Whole blood was immediately centrifuged, and plasma was stored at -80°C. Plasma carprofen concentration was measured at day 2, week 2 and then monthly for 6 months using reversed-phase high-performance liquid chromatography. The measured carprofen concentrations were analysed statistically using a linear mixed effects model. RESULTS: There was no effect of storage time over 6 months (p = 0.891) on measured carprofen levels. Although there was an effect of sampling timepoint (0, 1 and 6 h) (p < 0.001), the interaction between storage timepoint and sampling timepoint was not statistically significant (p = 1). CONCLUSIONS: Carprofen-laden canine plasma samples can be stored for up to 6 months before analysis with no degradation in carprofen concentrations expected.

Reflecting on the past and fast forwarding to present day anthelmintic resistant Ancylostoma caninum-A critical issue we neglected to forecast.

Reports of anthelmintic resistance in Ancylostoma caninum are increasing in frequency in the United States of America (USA). In the last few years in vitro and in vivo studies characterized individual isolates, demonstrating multiple anthelmintic drug resistance (MADR). In 2021, the American Association of Veterinary Parasitologists initiated a hookworm task force to address this issue. The first report of drug resistant A. caninum occurred in 1987 in Australian racing Greyhounds. In the last five years multiple case reports and investigations show drug resistant A. caninum is becoming a much greater problem in the USA and now extends beyond racing Greyhounds into the general companion animal dog population. The literature, regarding drug resistance in livestock and equine nematodes, provides helpful guidance along with diagnostic methods to better understand the evolution and selection of canine MADR hookworms; however, there are limitations and caveats due to A. caninum's unique biology and zoonotic potential. Mass drug administration (MDA) of anthelminthic drugs to humans to reduce morbidity associated with human hookworms (Necator americanus) should consider the factors that contributed to the development of MADR A. caninum. Finally, as Greyhound racing undergoes termination in some regions and the retired dogs undergo subsequent rehoming, drug resistant parasites, if present, are carried with them. Drug resistant A. caninum requires greater recognition by the veterinary community, and small animal practitioners need to be aware of the spread into current pet dog populations. The current understanding of anthelmintic resistance, available treatments, and environmental mitigation for these drug resistant A. caninum isolates must be monitored for horizontal spread. A major goal in this emerging problem is to prevent continued dissemination.

Pharmacokinetics and pharmacodynamics of intramuscular dexmedetomidine in dogs.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of dexmedetomidine after IM administration in dogs. ANIMALS: 6 healthy adult purpose-bred dogs (3 males, 3 females) with a mean ± SD body weight of 25.2 ± 1.8 kg. PROCEDURES: Each dog received 10 µg/kg dexmedetomidine, IM. Heart rate and respiratory rate were counted via cardiac auscultation and visual assessment of chest excursions. Sedation was assessed utilizing 2 sedation scoring systems. Plasma concentrations were determined using ultra performance liquid chromatography-mass spectrometry. Plasma concentrations versus time data after IM dexmedetomidine were analyzed using noncompartmental analysis for extravascular administration. RESULTS: Over the first 2 hours following IM injection of dexmedetomidine, plasma concentrations fluctuated in each dog. The geometric mean (range) maximum plasma concentration was 109.2 (22.4 to 211.5) ng/mL occurring at 20.5 (5 to 75) minutes, and the mean half-life was 25.5 (11.5 to 41.5) minutes. Heart rate was significantly lower than baseline from 30 minutes to 2 hours postdexmedetomidine administration, and respiratory rate was significantly lower than baseline from 45 minutes to 1.75 hours. Dogs were significantly more sedated from 30 minutes to 1.5 hours postdexmedetomidine administration. Median time to onset of sedation was 7.5 minutes (range, 2 to 10 minutes), and median time to peak sedation was 30 minutes (range, 15 to 60 minutes). CLINICAL RELEVANCE: Variations in plasma concentrations occurred in all dogs for the 2 hours postinjection of dexmedetomidine at 10 µg/kg, IM. This was likely due to alterations in absorption due to dexmedetomidine-induced local vasoconstriction. Despite variable plasma concentrations, all dogs were sedated following IM dexmedetomidine administration.

Effects of intravenous magnesium sulfate on serum calcium-regulating hormones and plasma and urinary electrolytes in healthy horses.

Intravenous magnesium sulfate (MgSO4) is used in equine practice to treat hypomagnesemia, dysrhythmias, neurological disorders, and calcium dysregulation. MgSO4 is also used as a calming agent in equestrian events. Hypercalcemia affects calcium-regulating hormones, as well as plasma and urinary electrolytes; however, the effect of hypermagnesemia on these variables is unknown. The goal of this study was to investigate the effect of hypermagnesemia on blood parathyroid hormone (PTH), calcitonin (CT), ionized calcium (Ca2+), ionized magnesium (Mg2+), sodium (Na+), potassium (K+), chloride (Cl-) and their urinary fractional excretion (F) after intravenous administration of MgSO4 in healthy horses. Twelve healthy female horses of 4-18 years of age and 432-600 kg of body weight received a single intravenous dose of MgSO4 (60 mg/kg) over 5 minutes, and blood and urine samples were collected at different time points over 360 minutes. Plasma Mg2+ concentrations increased 3.7-fold over baseline values at 5 minutes and remained elevated for 120 minutes (P < 0.05), Ca2+ concentrations decreased from 30-60 minutes (P < 0.05), but Na+, K+ and Cl- concentrations did not change. Serum PTH concentrations dropped initially to rebound and remain elevated from 30 to 60 minutes, while CT concentrations increased at 5 minutes to return to baseline by 10 minutes (P < 0.05). The FMg, FCa, FNa, FK, and FCl increased, while urine osmolality decreased from 30-60 minutes compared baseline (P < 0.05). Short-term experimental hypermagnesemia alters calcium-regulating hormones (PTH, CT), reduces plasma Ca2+ concentrations, and increases the urinary excretion of Mg2+, Ca2+, K+, Na+ and Cl- in healthy horses. This information has clinical implications for the short-term effects of hypermagnesemia on calcium-regulation, electrolytes, and neuromuscular activity, in particular with increasing use of Mg salts to treat horses with various acute and chronic conditions as well as a calming agent in equestrian events.

Iron robbery by intracellular pathogen via bacterial effector-induced ferritinophagy.

Iron is essential for survival and proliferation of Ehrlichia chaffeensis, an obligatory intracellular bacterium that causes an emerging zoonosis, human monocytic ehrlichiosis. However, how Ehrlichia acquires iron in the host cells is poorly understood. Here, we found that native and recombinant (cloned into the Ehrlichia genome) Ehrlichia translocated factor-3 (Etf-3), a previously predicted effector of the Ehrlichia type IV secretion system (T4SS), is secreted into the host cell cytoplasm. Secreted Etf-3 directly bound ferritin light chain with high affinity and induced ferritinophagy by recruiting NCOA4, a cargo receptor that mediates ferritinophagy, a selective form of autophagy, and LC3, an autophagosome biogenesis protein. Etf-3-induced ferritinophagy caused ferritin degradation and significantly increased the labile cellular iron pool, which feeds Ehrlichia Indeed, an increase in cellular ferritin by ferric ammonium citrate or overexpression of Etf-3 or NCOA4 enhanced Ehrlichia proliferation, whereas knockdown of Etf-3 in Ehrlichia via transfection with a plasmid encoding an Etf-3 antisense peptide nucleic acid inhibited Ehrlichia proliferation. Excessive ferritinophagy induces the generation of toxic reactive oxygen species (ROS), which could presumably kill both Ehrlichia and host cells. However, during Ehrlichia proliferation, we observed concomitant up-regulation of Ehrlichia Fe-superoxide dismutase, which is an integral component of Ehrlichia T4SS operon, and increased mitochondrial Mn-superoxide dismutase by cosecreted T4SS effector Etf-1. Consequently, despite enhanced ferritinophagy, cellular ROS levels were reduced in Ehrlichia-infected cells compared with uninfected cells. Thus, Ehrlichia safely robs host cell iron sequestered in ferritin. Etf-3 is a unique example of a bacterial protein that induces ferritinophagy to facilitate pathogen iron capture.

An intracellular nanobody targeting T4SS effector inhibits Ehrlichia infection.

Infection with obligatory intracellular bacteria is difficult to treat, as intracellular targets and delivery methods of therapeutics are not well known. Ehrlichia translocated factor-1 (Etf-1), a type IV secretion system (T4SS) effector, is a primary virulence factor for an obligatory intracellular bacterium, Ehrlichia chaffeensis In this study, we developed Etf-1-specific nanobodies (Nbs) by immunizing a llama to determine if intracellular Nbs block Etf-1 functions and Ehrlichia infection. Of 24 distinct anti-Etf-1 Nbs, NbD7 blocked mitochondrial localization of Etf-1-GFP in cotransfected cells. NbD7 and control Nb (NbD3) bound to different regions of Etf-1. Size-exclusion chromatography showed that the NbD7 and Etf-1 complex was more stable than the NbD3 and Etf-1 complex. Intracellular expression of NbD7 inhibited three activities of Etf-1 and E. chaffeensis: up-regulation of mitochondrial manganese superoxide dismutase, reduction of intracellular reactive oxygen species, and inhibition of cellular apoptosis. Consequently, intracellular NbD7 inhibited Ehrlichia infection, whereas NbD3 did not. To safely and effectively deliver Nbs into the host cell cytoplasm, NbD7 was conjugated to cyclized cell-permeable peptide 12 (CPP12-NbD7). CPP12-NbD7 effectively entered mammalian cells and abrogated the blockade of cellular apoptosis caused by E. chaffeensis and inhibited infection by E. chaffeensis in cell culture and in a severe combined-immunodeficiency mouse model. Our results demonstrate the development of an Nb that interferes with T4SS effector functions and intracellular pathogen infection, along with an intracellular delivery method for this Nb. This strategy should overcome current barriers to advance mechanistic research and develop therapies complementary or alternative to the current broad-spectrum antibiotic.

Complications and outcomes of swine that underwent cesarean section for resolution of dystocia: 110 cases (2013-2018).

OBJECTIVE: To report the surgical survival of dams and piglets and follow-up survival and future breeding potential of swine that underwent cesarean section for correction of dystocia. STUDY DESIGN: Retrospective study. ANIMALS: One hundred ten client-owned, female swine. All swine included in this study were breeding stock for market pigs to be used for exhibition purposes. METHODS: Medical records of swine that underwent cesarean section at The Ohio State University Hospital for Farm Animals for resolution of dystocia between January of 2013 and July of 2018 were reviewed. Signalment, history, number of piglets per litter, treatments, and surgical procedure were recorded. Follow-up information (survival, complications, and additional pregnancies) was obtained via telephone interview. RESULTS: A fetus was not palpable in 77 of 110 (70%) cases at presentation. The median litter size was eight piglets (range, 1-14), with medians of five (range, 0-13) live and one dead (range, 0-11) piglets per litter. Follow-up was available for 52 dams, of which 39 (75%) survived. Complications were recorded in 20 of 52 (38.46%) cases and included incisional seroma formation, lethargy, and anorexia. Twenty-three dams became pregnant and farrowed after the cesarean section, with no reported complication in 13 of these. CONCLUSION: Cesarean section in swine is associated with a good prognosis for recovery from the procedure and a fair to guarded prognosis for future breeding. CLINICAL SIGNIFICANCE: Cesarean section may be considered for resolution of dystocia in swine. However, owners should be advised that nearly half of sows require assistance in subsequent deliveries.

Plasma amino acid status is useful for understanding intestinal mucosal damage in calves with cryptosporidiosis.

We hypothesize that some amino acid abnormalities in diarrheic calves are useful for understanding intestinal mucosal damage, as in humans. However, few reports have revealed the relationship between intestinal mucosal damage and plasma amino acids in diarrheic calves. Therefore, the aim of present study was to investigate whether there is a relationship between the amino acid status and plasma diamine oxidase (DAO) activity, which is known to be a biomarker for intestinal mucosal damage in diarrheic calves. Twenty Holstein calves aged 12.6 ± 4.2 days old were enrolled in this study. In the diarrhea group (n = 10), there were yellow loose feces within the rectum and Cryptosporidium parvum (C. parvum) was detected in all fecal samples. These calves were clinically normal except for diarrhea. All calves in the control group (n = 10) appeared to be healthy based on clinical findings with normal feces production and the absence of C. parvum. Plasma amino acid concentrations and DAO activity were measured. The relationships between plasma DAO activity and the concentration of each plasma amino acid were investigated using Spearman's rank test. The plasma DAO activity was significantly lower in the diarrhea group (176.1 ± 60.1 IU mL-1) than in the control group (309.3 ± 74.8 IU mL-1) (p < 0.001). Furthermore, positive correlations were observed when comparing plasma DAO activity with histidine, proline, cystine, arginine, and glutamine concentrations. As a result of relationship between plasma DAO activity and amino acid status, it was concluded that plasma amino acid status is useful for understanding intestinal mucosal damage in calves with cryptosporidiosis.

Plasma histidine concentrations as a specific biomarker for intestinal mucosal damage in calves with cryptosporidiosis.

Specific alterations in plasma histidine concentrations and diamine oxidase (DAO) activity were recently reported as a potential biomarker for intestinal mucosal damage in diarrheic calves. However, there are no data on the comparison of precision between histidine concentration and DAO activity in bovine plasma. The aim of the present study was to compare precision of histidine concentrations and DAO activities in plasma as a biomarker for the Cryptosporidium parvum (C. parvum)-associated intestinal mucosal damage in diarrheic calves. Thirty-two Holstein calves aged 12.2 ± 4.1 days old were enrolled in the present study; they were divided into C. parvum (n = 9), diarrhea (n = 11), and control (n = 12) groups based on the presence or absence of diarrhea and with or without C. parvum infection. Receiver operating characteristic (ROC) curves were used to characterize the sensitivity and specificity of each parameter for the C. parvum-associated intestinal mucosal damage. The proposed cut-off points for plasma histidine concentrations and plasma DAO activities for cryptosporidiosis in calves based on ROC analyses were < 55.8 nM and < 246.0 IU/ml, respectively. The sensitivities and specificities of the proposed diagnostic cut-offs were 88.9% and 82.6% for plasma histidine concentrations and 100.0% and 34.8% for plasma DAO activities, respectively. It was concluded that plasma histidine concentrations may be superior to plasma DAO activities as a specific biomarker for the C. parvum-associated intestinal mucosal damage in diarrheic calves.

Sequential changes in hepatic mRNA abundance and serum concentration of serum amyloid A in cattle with acute inflammation caused by endotoxin.

The objective of the present study was to elucidate sequential changes in mRNA abundance of serum amyloid A (SAA) isotypes in endotoxin (ETX) challenge model cattle. Ten healthy cattle were separated to 2 groups: control and ETX groups. Cattle in the ETX group were challenged by 2.5 µg/kg of O111:B4 lipopolysaccharide in 4 ml of autologous serum. Blood samples were withdrawn at pre, 0.5, 1, 2, 4, 8, 12, 24, 48, 72 and 96 hr after ETX challenge. Plasma ETX activity, serum SAA concentrations, mRNA abundance of interleukin (IL)-6, SAA2 and SAA4 in the liver and polymorphonuclear leukocytes were measured. The plasma ETX activity in the ETX group increased at 0.5 hr after the ETX challenge. The serum SAA value remained higher between 12 and 72 hr after the ETX challenge than that of the control group. Hepatic IL-6 mRNA abundance in the ETX group increased at 2 hr after the ETX challenge. Hepatic SAA2 and SAA4 mRNA abundance significantly increased from 4 hr after administration, and remained significantly higher than those pre-values up to 12 and 24 hr, respectively. The abundance ratio of hepatic SAA2 was much higher than that of SAA4. The major isotype was SAA2 in liver tissue, and it is indicating systemic inflammation in cattle.

Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia.

The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO4 ) to healthy horses. MgSO4 is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO4 at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitored and echocardiograms performed at predetermined times. Noncompartmental pharmacokinetic analysis was applied to plasma concentrations of ionized magnesium (Mg2+ ). Objective data were analyzed using the Wilcoxon rank-sum test with p < .05 used as a determination for significance. Plasma concentrations of Mg2+ increased nearly fivefold, ionized calcium (Ca2+ ) decreased by nearly 10%, and the Ca2+ to Mg2+ ratio declined more than 3.5-fold and remained different than baseline until 24 hr (p < .05). Significant changes were seen with urinary fractional excretion of electrolytes, cardiovascular parameters, and echocardiographic measurements. No changes were detected in CSF electrolyte concentrations. The decrease in Ca2+ result of hypermagnesemia supports the interaction between these cations. Alterations detected in plasma electrolyte concentrations and urinary fractional excretion of electrolytes may serve as biomarkers for regulatory control for the nefarious administration of MgSO4 .

Effectiveness of tapentadol hydrochloride for treatment of orthopedic pain in dogs: A pilot study.

This pilot study evaluated the short-term analgesic effect of oral tapentadol hydrochloride (tapentadol) in dogs with unilateral hind limb lameness secondary to naturally occurring cranial cruciate ligament rupture. Baseline data including pharmacodynamic parameters, sedation scores, lameness scores, and objective gait analyses were collected. Tapentadol was administered orally (30 mg/kg body weight). Four hours following administration of tapentadol all data were collected again. Plasma concentrations of tapentadol 4 hours after administration were assessed using high performance liquid chromatography tandem mass spectrometry. No significant side effects were noted. All dogs had measurable plasma concentrations of tapentadol (mean concentration: 18.9 ng/mL). There were no significant differences in pharmacodynamic parameters or sedation over time. Subjective lameness scores were significantly lower than baseline at 4 hours post-drug administration. No significant improvement was seen in objective gait analysis. Further studies are needed to assess dosing regimens which may lead to effective treatment of acute pain and long-term use.

Efficacité de l'hydrochlorure de tapentadol pour le traitement de douleur orthopédique chez des chiens : une étude pilote. La présente étude pilote a évalué l'effet analgésique à court terme d'hydrochlorure de patentadol (tapentadol) chez des chiens avec une boiterie unilatérale d'un membre arrière secondaire à une rupture du ligament croisé antérieur se produisant naturellement. Les données de base obtenues incluaient des paramètres pharmacodynamiques, des pointages de sédation, des pointages de boiterie et des analyses objectives de la posture. Du tapentadol fut administré oralement (30 mg/kg de poids corporel). Quatre heures suivant l'administration de tapentadol toutes les données furent prises à nouveau. Les concentrations plasmatiques de tapentadol 4 heures après l'administration furent déterminées en utilisant la chromatographie à haute performance en phase liquide en tandem avec la spectrométrie de masse. Aucun effet secondaire significatif ne fut noté. Tous les chiens avaient des concentrations plasmatiques mesurables de tapentadol (concentration moyenne : 18,9 ng/mL). Il n'y avait pas de différence significative dans le temps pour les paramètres pharmacodynamiques ou la sédation. Les pointages subjectifs de boiterie 4 heures postadministration du médicament étaient significativement plus faibles que les valeurs de base. Aucune amélioration significative ne fut observée dans l'analyse objective de la posture. Des études supplémentaires sont requises pour évaluer les régimes de dosage qui pourraient mener à un traitement efficace de la douleur aiguë et de l'utilisation à long-terme.(Traduit par Dr Serge Messier).

Pharmacokinetics of an intravenous constant rate infusion of a morphine-lidocaine-ketamine combination in Holstein calves undergoing umbilical herniorrhaphy.

OBJECTIVE: To describe the pharmacokinetics of morphine, lidocaine, and ketamine associated with IV administration of a constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination to calves undergoing umbilical herniorrhaphy. ANIMALS: 20 weaned Holstein calves with umbilical hernias. PROCEDURES: Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 µg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). For all calves, the CRI was begun after anesthesia induction. Blood samples were obtained immediately before and at predetermined times for 120 hours after initiation of the assigned treatment. Noncompartmental analysis was used to estimate pharmacokinetic parameters for the MLK group. RESULTS: During the CRI, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine. Mean terminal half-life was 4.1, 0.98, and 1.55 hours and area under the concentration-time curve was 41, 14,494, and 7,426 h•µg/mL for morphine, lidocaine, and ketamine, respectively. After the CRI, the mean serum drug concentration at steady state was 6.3, 616.7, and 328 ng/mL for morphine, lidocaine, and ketamine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: During the CRI of the MLK solution, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine, likely owing to the fairly long half-life of morphine. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols.

Analgesic efficacy of an intravenous constant rate infusion of a morphine-lidocaine-ketamine combination in Holstein calves undergoing umbilical herniorrhaphy.

OBJECTIVE: To assess the analgesic efficacy of an IV constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination in calves undergoing umbilical herniorrhaphy. ANIMALS: 20 weaned Holstein calves with umbilical hernias. PROCEDURES: Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 µg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). The assigned CRI was begun after anesthesia induction. A pain-scoring system and incisional algometry were used to assess pain, and blood samples were obtained to measure serum cortisol concentration at predetermined times for 120 hours after CRI initiation. RESULTS: Mean pain scores did not differ significantly between the MLK and control groups at any time. Mean algometry score for the MLK group was significantly greater (calves were less responsive to pressure) than that for the control group at 4 hours after CRI initiation. Mean cortisol concentration decreased over time for both groups and was significantly greater for the MLK group than the control group at 1, 4, and 18 hours after CRI initiation. CONCLUSIONS AND CLINICAL RELEVANCE: A CRI of MLK provided adequate postoperative analgesia to calves that underwent umbilical herniorrhaphy. However, the technical support required for CRI administration limits its use to hospital settings. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols and withdrawal intervals.

Radio-Telemetric Assessment of Cardiac Variables and Locomotion With Experimentally Induced Hypermagnesemia in Horses Using Chronically Implanted Catheters.

The objective of this study was to characterize the pharmacokinetics and pharmacodynamics of intravenous administration of magnesium sulfate to horses using a novel radio-telemetry system for physiologic signal capture. Five Horses were surgically implanted with a radio-telemetric carotid catheter. Implants were paired with a non-invasive telemetric unit which acquired a six lead ECG and 3-axis acceleration to assess activity acquired wirelessly in real-time for future analysis. Horses were exposed to a new stall environment before (baseline) and after 60 mg/kg (30 mL) of magnesium sulfate (MgSO4), or the same volume of 0.9% saline, administered intravenously in a blinded, random crossover design. Blood for pharmacokinetics, telemetric data, and body temperature were recorded serially for 24 h. Data were analyzed across time and between treatments. Significance was set at P < 0.05. Ionized magnesium concentration (Mg2+) increased and the Ca2+ to Mg2+ ratio decreased and persisted for 5 h after MgSO4 administration. Heart rate (HR) increased and mean arterial blood pressure (MAP) decreased for at least 6 h. Electrocardiogram (ECG) intervals (RR) decreased and (PR and QTc) increased in duration compared to controls indicating an increase in heart rate, and slower myocardial conduction in the MgSO4 group. Acceleration in all planes was less in the MgSO4 group compared to controls indicating decreased locomotion. This novel method permitted collection of physiologic signals without interference by handlers or animal restraint. An intravenous bolus of MgSO4 produced cardiac variable changes associated with the reduction of locomotion in these horses, and in a direction that may be causal. Locomotion was decreased when horses were first introduced into a new environment which reflects the calming effect desired in sport horses. Telemetric monitoring can be used as a model to elucidate the behavior and physiologic effects of other drugs. The administration of MgSO4 may be detected for regulatory purposes with the monitoring of Mg2+ and Ca2+ concentrations and their ratio.

Pharmacokinetics and pharmacodynamic effects of oral transmucosal and intravenous administration of dexmedetomidine in dogs.

OBJECTIVE: To determine pharmacokinetic and pharmacodynamic properties of the injectable formulation of dexmedetomidine administered via the oral transmucosal (OTM) route to healthy dogs. ANIMALS: 6 healthy dogs. PROCEDURES: Injectable dexmedetomidine was administered IV (5 µg/kg) or via the OTM route (20 µg/kg) in a blinded, single-observer, randomized crossover study. Dogs received dexmedetomidine and a sham treatment at each administration. Serial blood samples were collected from a catheter in a saphenous vein. Heart rate, respiratory rate, and subjective sedation score were assessed for 24 hours after administration. Plasma samples were analyzed for dexmedetomidine concentrations by use of ultraperformance liquid chromatography-tandem mass spectrometry. RESULTS: For the OTM route, the mean ± SD maximum plasma concentration was 3.8 ± 1.3 ng/mL, which was detected 73 ± 33 minutes after administration. The mean maximum concentration for the IV dose, when extrapolated to the time of administration, was 18.6 ± 3.3 ng/mL. The mean terminal-phase half-life was 152 ± 146 minutes and 36 ± 6 minutes for OTM and IV administration, respectively. After IV administration, total clearance was 8.0 ± 1.6 mL/min/kg and volume of distribution at steady state was 371 ± 72 mL/kg. Bioavailability for OTM administration of dexmedetomidine was 11.2 ± 4.5%. Peak sedation scores did not differ significantly between routes of administration. Decreases in heart rate, respiratory rate, and peak sedation score were evident sooner after IV administration. CONCLUSIONS AND CLINICAL RELEVANCE: OTM administration of the injectable formulation of dexmedetomidine resulted in a similar degree of sedation and prolonged duration of action, compared with results for IV administration, despite relatively low bioavailability.

Investigation of a novel prosthesis technique for extracapsular stabilization of cranial cruciate ligament-deficient stifle joints in adult cattle.

OBJECTIVE: To evaluate a novel prosthesis technique for extracapsular stabilization of cranial cruciate ligament (CCL)-deficient stifle joints in adult cattle. SAMPLE: 13 cadaveric bovine stifle joint specimens. PROCEDURES: In the first of 3 study phases, the most isometric points on the distal aspect of the femur (distal femur) and proximal aspect of the tibia (proximal tibia) were determined from measurements obtained from lateromedial radiographs of a stifle joint specimen maintained at angles of 135°, 90°, 65°, and 35°. During phase 2, 800-lb-test monofilament nylon leader line was cut into 73-cm-long segments. Each segment was secured in a loop by use of 2, 3, or 4 crimping sleeves such that there were 12 replicates for each construct. Each loop was distracted to failure at a constant rate of 1 mm/s. Mean force at failure and elongation and mode of failure were compared among the 3 constructs. During phase 3, bone tunnels were created in the distal femur and proximal tibia at the isometric points identified during phase 1 in each of 12 CCL-deficient stifle joint specimens. The 3-sleeve construct was applied to each specimen. Specimens were distracted to failure at a constant rate of 1 mm/s. RESULTS: Among the 3 constructs evaluated, the 3-sleeve construct was considered optimal in terms of strength and amount of foreign material. In phase 3, all replicates failed because of suture slippage. CONCLUSIONS AND CLINICAL RELEVANCE: Use of 800-lb-test monofilament nylon leader line as a prosthesis might be a viable alternative for extracapsular stabilization of CCL-deficient stifle joints in adult cattle. Further in vivo studies are necessary.

Pharmacokinetics and pharmacodynamics of intranasal and intravenous naloxone hydrochloride administration in healthy dogs.

OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of naloxone hydrochloride in dogs following intranasal (IN) and IV administration. ANIMALS: 6 healthy adult mixed-breed dogs. PROCEDURES: In a blinded crossover design involving 2 experimental periods separated by a washout period (minimum of 7 days), dogs were randomly assigned to receive naloxone IN (4 mg via a commercially available fixed-dose naloxone atomizer; mean ± SD dose, 0.17 ± 0.02 mg/kg) or IV (0.04 mg/kg) in the first period and then the opposite treatment in the second period. Plasma naloxone concentrations, dog behavior, heart rate, and respiratory rate were evaluated for 24 hours/period. RESULTS: Naloxone administered IN was well absorbed after a short lag time (mean ± SD, 2.3 ± 1.4 minutes). Mean maximum plasma concentration following IN and IV administration was 9.3 ± 2.5 ng/mL and 18.8 ± 3.9 ng/mL, respectively. Mean time to maximum concentration following IN administration was 22.5 ± 8.2 minutes. Mean terminal half-life after IN and IV administration was 47.4 ± 6.7 minutes and 37.0 ± 6.7 minutes, respectively. Mean bioavailability of naloxone administered IN was 32 ± 13%. There were no notable changes in dog behavior, heart rate, or respiratory rate following naloxone administration by either route. CONCLUSIONS AND CLINICAL RELEVANCE: Use of a naloxone atomizer for IN naloxone administration in dogs may represent an effective alternative to IV administration in emergency situations involving opioid exposure. Future studies are needed to evaluate the efficacy of IN naloxone administration in dogs with opioid intoxication, including a determination of effective doses.

Short- and long-term success of transfixation pin casts used to stabilize long bone fractures in ruminants.

Transfixation pin casts (TPC) may be useful in management of fractures in ruminants. A retrospective study was conducted to report the uses, complications, and outcomes of TPC in ruminant fracture stabilization. Twenty-five cattle, 7 goats, and 7 sheep with long bone fractures managed with TPC met the inclusion criteria. Long-term outcome was assessed from telephone interviews with owners. Thirty-one animals (79%) survived to removal of external coaptation and return to the farm. Common complications included pin-hole osteitis and disuse osteopenia. Common complications resulting in death or euthanasia included osteomyelitis and non-union and pin tract fracture. Animals with increased body weight had a greater odds of dying or being euthanized. Cattle had a decreased odds of dying or being euthanized compared with goats and sheep. Long-term follow-up was available for 20 patients, 17 of which returned to intended use and 12 of which had no residual lameness.

Succès à court et à long terme des plâtres à broche transfixiante utilisés pour stabiliser les fractures d'os longs chez les ruminants. Les plâtres à broche transfixiante (PBT) peuvent être un outil utile pour la gestion des fractures des ruminants. Une étude rétrospective a été réalisée afin de faire rapport sur les utilisations, les complications et les résultats des PBT pour la stabilisation des fractures des ruminants. Vingt-cinq bovins, 7 chèvres et 7 moutons avec des fractures d'os longs gérée par PBT ont satisfait aux critères d'inclusion. Les résultats à long terme ont été évalués par entrevue téléphonique avec les propriétaires. Trente-et-un (79 %) animaux ont survécu à l'enlèvement de la coaptation externe et sont retournés à la ferme. Les complications communes incluaient l'ostéite du trou de la broche et l'ostéopénie par inaction. Les complications communes se traduisant par la mort ou l'euthanasie incluaient l'ostéomyélite, la non-union et la fracture causée par la broche. Les animaux ayant un poids supérieur présentaient plus de risques de mortalité ou d'euthanasie. Les bovins présentaient des risques réduits de mortalité ou d'euthanasie comparativement aux chèvres et aux moutons. Le suivi à long terme était disponible pour 20 patients et 17 d'entre eux sont retournés à leur usage prévu et 12 n'avaient pas de boiterie résiduelle.(Traduit par Isabelle Vallières).

Safety and serologic response to a Haemonchus contortus vaccine in alpacas.

Haemonchosis in camelids remains a challenging disease to treat, and prevention has become increasingly problematic due to widespread anthelmintic resistance. Barbervax®is an adjuvanted vaccine containing natural H-11, H-gal-GP antigens obtained from Haemonchus contortus adults via a proprietary process and solubilized in Quil A. This vaccine is approved for use in Australia, after demonstrating its safety and efficacy in sheep and goats. There are no published studies evaluating Barbervax in other ruminants/pseudoruminants such as camelids which can be parasitized with H. contortus. The vaccine utilizes a mixture of the parasite gut mucosal membrane enzymes including H-gal-GP and H11, involved in digesting a blood meal from the host. This study monitored the safety profile of the Barbervax® vaccine in a group of adolescent alpacas. Although designed into the original study of vaccine efficacy, the experimental infection with viable H. contortus third stage larvae could not be completed due to lack of detectable significant variation of infection following experimental challenge. Twelve alpacas (158 + 15 days) were randomized to vaccination with Barbervax® or no treatment. Three doses of Barbervax® were administered at 3 week intervals and investigators involved in animal monitoring and sample collection were blinded to the groupings. Clinical pathologic parameters were evaluated 7 days before vaccination, and 1 and 2 months post-vaccination. Daily clinical observations were made and specific observations regarding the injection site and rectal temperatures were monitored in each alpaca twice daily for 1 week following vaccination. Fecal egg counts, packed cell volume, and total protein were monitored following challenge with 1500 H. contortus larvae on days 42, 46, and 50. An increase in rectal temperature for a duration of 2 days (range 2-4 days) was observed post-vaccination. Vaccinated alpacas were lethargic for 2-3 days following vaccination; however, they maintained an appetite and no visible or palpable injection site reactions were observed. Following the first vaccination, all animals maintained normal clinical pathologic parameters throughout the study period. The vaccinated animals did develop titers to the H. contortus antigen as measured by ELISA. In conclusion, the Barbervax® vaccine demonstrated safety in this small group of young, healthy alpacas, but additional studies are required to evaluate the efficacy of the vaccine under field conditions in protecting alpacas against infection with H. contortus.