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Simple Summary: Cannabidiol, better known as simply CBD, is one of the non-psychoactive compounds found in hemp. Its supplementation to horses is gaining in popularity as a potential alternative to conventional pharmaceutical treatments for a variety of conditions such as arthritis and anxiety. Despite potential advantages of CBD supplementation, it may have a negative impact on equine health and performance. More scientific research is needed to form recommendations for its use in horses; therefore, this study was designed to investigate supplementation of CBD oil over 28 days in 30 horses. Targeted levels of supplementation were to provide three levels for comparison (0.0 mg/kg, 0.75 mg/kg, or 1.50 mg/kg); however, the supplements collected during the study were analyzed to be substantially lower than targeted levels when tested at a verified testing facility (0.12 mg/kg and 0.13 mg/kg). At this level of supplementation, CBD oil was well-accepted, CBD was not detectible in blood samples, and blood chemistry parameters to assess liver and kidney function were not adversely affected as a result of supplementation. However, more research is needed to describe the discrepancy between formulated levels compared to tested levels of CBD supplements, in order to make recommendations for its application in the horse industry. Thirty stock type geldings (15 ± 3 years; 556 ± 63 kg BW) were used in a randomized complete design over 28 days to determine the influence of cannabidiol (CBD) oil supplementation levels on body weight, body condition, and blood chemistry. Horses were randomly assigned to one of three dietary treatments (n = 10 per treatment) formulated with canola oil to provide 1.50 mg CBD/kg BW (TRTA), 0.75 mg CBD/kg BW (TRTB), or 0.00 mg CBD/kg BW (canola oil; CTRL). Treatments were top-dressed onto concentrate and individually administered twice daily. Horses were maintained in adjacent dry lots and received coastal bermudagrass hay ad libitum. Body weight and body condition scores (BCS) were obtained every 14 days. On day 0 and 28, blood was collected via jugular venipuncture and serum was harvested to perform a blood chemistry panel and drugs of abuse screening at the Texas Veterinary Medical Diagnostic Laboratory. Data were analyzed using PROC MIXED of SAS (v9.4), and the model included treatment, time, and the treatment × time interaction, and linear and quadratic orthogonal polynomial contrasts to partition sum of squares. Analysis of composited treatment samples revealed lower CBD concentrations than indicated from initial testing by the manufacturer (0.13 mg CBD/kg in TRTA; 0.12 mg CBD/kg in TRTB). At this level of supplementation, canola-based CBD oil was well-accepted by mature horses, banned substances were not detectable in blood, and blood chemistry parameters were not adversely affected as a result of supplementation. More research is warranted to describe the discrepancy between formulated levels compared to tested levels of CBD in the canola-based supplement. [ABSTRACT FROM AUTHOR]

Concerns over the extra-label use of bisphosphonates in skeletally immature horses has extended to include its likely re-release from bone into circulation in response to stressors. Therefore, the objective of this study was to be first to quantify the re-release of clodronate in response to controlled stressors. Yearling Quarter horses (n = 32) were stratified by age, body weight (BW), sex, and initial bone optical density into four treatment groups for a 168-d trial. Treatments consisted of control (CON; n = 8), single-dose (1X; d 84; n = 8), 2-dose (2X; d 0 and 84; n = 8), and four-dose groups (4X; d 0, 42, 84, and 126; n = 8). All horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW clodronate disodium (OSPHOSÒ) or saline (placebo) on d 0, 42, 84, and 126. Horses were housed in individual stalls (3.6 m × 7.2 m). Diets were formulated to meet nutrient requirements including concentrate offered every 12-h and ad libitum coastal bermudagrass (Cynodon dactylon) hay and water. Horses were exercised 5 d/ wk with a progressive workload, and maximum exercise intensity was reached on d 120, verified via heart rate and blood lactate. On d 120, blood samples were collected prior to the start of the exercise bout (pre), and 0-, 0.5-, 1-, 3-, 12-, and 24-h post exercise. Both tuber coxae of each horse were biopsied on d 168 with blood samples collected prior to (pre), and 0, 12, 24, 48, 72, 168, and 336 h post biopsy. Clodronate was quantified in plasma from exercise and biopsy samples using liquid chromatography tandem mass spectrometry. Exercise and biopsy serum were analyzed for cortisol, a marker of stress, while biopsy serum was analyzed for substance P, a pain marker. Data were analyzed using SAS PROC MIXED. Exercise did not result in clodronate re-release as there was no treatment x time interaction or time effect (P ≥ 0.44), but clodronate was dose-dependently greater in treated groups throughout the exercise collection period (P < 0.01). A treatment x time interaction (P ≤ 0.01) was observed for clodronate concentrations surrounding bone biopsy in which concentrations decreased at 168 h post biopsy before increasing at 336 h in 4X horses. Substance P increased over time (P < 0.01) following biopsy, regardless of treatment. Despite decreasing over time (P ≤ 0.01), there were similarly no treatment differences (P ≥ 0.46) nor treatment ´ time interactions (P ≥ 0.78) for cortisol following either exercise or bone insult. In conclusion, submaximal exercise did not result in re-release of clodronate; however, direct bone insult disrupted clodronate concentrations in horses receiving 4 administrations of bisphosphonate despite no treatment impact on stress or pain indicators. [ABSTRACT FROM AUTHOR]

Bisphosphonates alter bone metabolism via inhibition of osteoclastic bone resorption. Although bisphosphonates are beneficial to treat bone disease, extra-label use in healthy juvenile horses may interfere with normal bone metabolism. The objective was to determine plasma pharmacokinetics of the bisphosphonate clodronate disodium (CD) following a single intramuscular dose to better define the time course of CD in juvenile horses. Ten yearling Quarter Horses (334 ± 18 kg, 504 ± 13 d of age) were used to test the hypothesis that juvenile horses would have faster clearance rate of CD compared with previously published data in adult horses. Horses were placed in individual stalls, jugular intravenous catheters were inserted, and an initial blood sample (0 h) was collected. Horses were administered CD intramuscularly at 1.8 mg/kg BW per label. Plasma samples were collected at 0.5, 1, 3, 6, 12, 24, 48, and 72 h post-administration. Plasma concentration of clodronate was determined by liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using a two-compartment model. Blood chemistry parameters [blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALKP), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and creatine kinase (CK)] were determined via a commercial laboratory. Included blood chemistry parameters were analyzed for an effect of time using PROC Mixed of SAS. Clodronate was detected in plasma up to 72 h post-administration. Maximum plasma concentration (43,971 ± 25,920 ng/mL) was reached at 0.5 h postadministration. Analysis revealed bicompartmental kinetics with distribution and terminal half-lives of 1.9 ± 0.4 h and 24.4 ± 4.3 h, respectively. Area under the curve to last sample was 22,755 ± 11,426 ng*h/mL and extrapolated to infinity was 26,778 ± 12,465 ng*h/mL. Blood chemistry parameters varied over time within normal ranges. Markers of renal function, BUN and creatinine, decreased from h 0 to h 72 (P < 0.01). Liver function markers ALKP and AST were not affected by CD treatment (P > 0.27). However, GGT and CK changed over time (P < 0.01), with GGT greater at 48 h than other time points, and CK increasing from 0.5 to 24 h before decreasing by 72 h but remaining above baseline. Plasma clodronate concentrations were greater in juvenile horses than previously reported in mature horses (Krueger et al., 2020, Equine Vet J.; Knych et al., 2022, Equine Vet J.). Further, the observed bicompartmental kinetics differed from the linear kinetics previously reported in mature horses whereby juvenile horses from the current study had greater exposure to CD over time as indicated by a longer terminal half-life. Moreover, the single intramuscular dose of CD (1.8 mg/kg BW) did not cause markers of kidney or liver function to deviate from normal ranges in juvenile Quarter Horses. [ABSTRACT FROM AUTHOR]

Background: Although Beef Quality Assurance guidelines do not recommend use of darting methods to deliver drugs, cattle in the US may be raised on farms and ranches without restraint facilities, and reports from the field suggest that dart guns are being used to deliver antimicrobial drugs. Few studies report whether this route of administration results in altered drug disposition or carcass quality. Methods: Forty steers were blocked by sire and then randomly assigned to treatment with saline, ceftiofur crystalline free acid, tildipirosin, or tulathromycin delivered via dart gun. To assess drug disposition, eight ceftiofur, six tulathromycin, and six tildipirosin-treated calves were selected to measure plasma concentrations of drugs up to 10 days after drug administration. Steers were then fed a balanced ration for approximately 6.5 months and slaughtered. To evaluate carcass quality, tenderness of steaks from darted-side and non-darted sides was evaluated via Warner–Bratzler shear force testing. Due to the prohibition of extralabel routes of administration for ceftiofur in the U.S., animals treated with this drug did not enter the food supply. Results: Ceftiofur disposition differed from published reports with lower mean Cmax but similar mean apparent elimination half-life. Tildipirosin disposition differed from published reports with lower Cmax and shorter apparent elimination half-life. Tulathromycin was similar to previous published reports but Cmax and apparent elimination half-life was highly variable. All steaks (from darted and non-darted sides) from cattle treated with ceftiofur and saline were more tender than from cattle treated with tulathromycin or tildipirosin (P = 0.003). There was a trend toward more tenderness in steaks from the non-darted compared to the darted side. Steaks from the darted side for one treatment, tildipirosin, were less tender than the non-darted side. Conclusions: Pharmacokinetic parameters of ceftiofur crystalline free acid, tildipirosin, and tulathromycin to cattle using pressure-adjustable pneumatic gas-powered dart gun were estimated in this study. Delivery of tildipirosin and tulathromycin to cattle with dart gun may also result in detectable decreases in tenderness of harvested steaks. [ABSTRACT FROM AUTHOR]

The tranquilizer combination of butorphanol, azaperone, and medetomidine (BAM) has shown good efficacy for immobilization of wildlife, including black bears (Ursus americanus). BAM is antagonized with a combination of naltrexone and atipamezole. We immobilized 19 adult captive wild caught black bears and, except for three bears that were euthanized immediately, bears were recovered with naltrexone and atipamezole. Tissue residues (≥0.01 ppm) for the tranquilizers butorphanol, azaperone, and medetomidine were detected in liver and muscle of all three bears euthanized on day 0 postinjection (PI). Azaperone was not detected after 1 d PI. Residue for medetomidine was detected in two bears: in the liver 3 d PI and in the kidney 6 d PI. Butorphanol was reported in three bears: in fat 5 d PI, in kidney 6 d PI, and, surprisingly, in kidney, muscle, and fat 7 d PI. No tissue residues were detected in the three bears euthanized at 8 d PI. Tissue residues for the antagonists, naltrexone and atipamezole, were detected in bears euthanized 2 and 6 d PI, but not in tissues from animals euthanized at 7 or 8 d PI. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the likelihood that swine treated with flunixin meglumine could contaminate their environment, which could cause untreated swine housed in the same pen to ingest or absorb enough drug to be detected in their urine. Currently, any detectable level of flunixin found in the urine of pigs exhibited at livestock shows in Texas can disqualify the exhibitor. We conducted 2 trials in this study. The first, a pilot trial, placed pigs in 2 pens, with each pen housing a pig that did not receive a drug and a treated pig that received 2.2 mg/kg of flunixin intramuscularly. This trial demonstrated that transfer of the drug from treated to untreated pigs housed in close proximity was possible. The second trial was conducted using 10 pens, with a treated and untreated pig in each pen. Each pig receiving treatment was randomly selected and administered 2.2 mg/kg of flunixin intramuscularly; then, urine and plasma were collected from all swine for 10 d. Flunixin was detected at or above the limit of detection of 0.1 ng/mL in the urine of all treated and untreated pigs throughout the 10-d trial. Treated pigs had higher urine levels of flunixin than their untreated pen mates for 4 d post-treatment (P < 0.0001), but there was no statistical difference between pen mates during the last 5 d of the trial, making it impossible to differentiate treated from untreated pigs. [ABSTRACT FROM AUTHOR]

Macrolides are important antimicrobials frequently used in human and veterinary medicine in the treatment of pregnant women and pregnant livestock. They may be useful for the control of infectious ovine abortion, which has economic, animal health, and human health impacts. In this study, catheters were surgically placed in the fetal vasculature and amnion of pregnant ewes at 115 (±2) days of gestation. Ewes were given a single dose of 2.5 mg/kg tulathromycin subcutaneously, and drug concentrations were determined in fetal plasma, maternal plasma, and amniotic fluid at 4, 8, 12, 24, 36, 48, 72, 144, and 288 hr after drug administration. Pharmacokinetic parameters in maternal plasma were estimated using noncompartmental analysis and were similar to those previously reported in nonpregnant ewes. Tulathromycin was present in fetal plasma and amniotic fluid, indicating therapeutic potential for use against organisms in these compartments, though concentrations were lower than those in maternal plasma. Time‐course of drug concentrations in the fetus was quite different than that in the ewe, with plasma concentrations reaching a plateau at 4 hr and remaining at this concentration for the remainder of the sampling period (288 hr), raising questions about how tulathromycin may be transported into or metabolized and eliminated by the fetus. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that nalbuphine, medetomidine, and azaperone (NalMed-A) can effectively immobilize adult elk ( Cervus elaphus nelsoni), and be antagonized using naltrexone and atipamezole, with or without tolazoline. To assess duration of tissue residues for this immobilization package, we immobilized 14 captive adult elk with NalMed-A, then euthanized animals and collected tissues 0, 3, 6, 14, 21, or 28 d later. Except for two animals euthanized immediately, all elk were recovered using naltrexone, atipamezole, and tolazoline. Tissue residues (≥0.01 parts per million) for the tranquilizers nalbuphine, medetomidine, and azaperone were detected in liver and muscle tissue samples from elk euthanized within 40 min postinjection (PI) and one animal that died 12−24 h PI, but not in tissues from any of the animals euthanized at 3, 6, 14, 21, or 28 d PI. Tissue residues for the antagonists naltrexone, atipamezole, and tolazoline were detected in liver and muscle of the animal that died 12−24 h PI. Only naltrexone was detected in liver from the two elk euthanized at day 3, and no antagonist residues were detected thereafter. [ABSTRACT FROM AUTHOR]

Background. Glyburide (also known as glibenclamide) is effective in reducing the severity of tissue destruction and improving functional outcome after experimental spinal cord injury in rodents and so has promise as a therapy in humans. There are many important differences between spinal cord injury in experimental animals and in human clinical cases, making it difficult to introduce new therapies into clinical practice. Spinal cord injury is also common in pet dogs and requires new effective therapies, meaning that they can act as a translational model for the human condition while also deriving direct benefits from such research. In this study we investigated the pharmacokinetics and safety of glyburide in dogs with clinical spinal cord injury. Methods. We recruited dogs that had incurred an acute thoracolumbar spinal cord injury within the previous 72 h. These had become acutely non-ambulatory on the pelvic limbs and were admitted to our veterinary hospitals to undergo anesthesia, cross sectional diagnostic imaging, and surgical decompression. Oral glyburide was given to each dog at a dose of 75 mcg/kg. In five dogs, we measured blood glucose concentrations for 10 h after a single oral dose. In six dogs, we measured serum glyburide and glucose concentrations for 24 h and estimated pharmacokinetic parameters to estimate a suitable dose for use in a subsequent clinical trial in similarly affected dogs. Results. No detrimental effects of glyburide administration were detected in any participating dog. Peak serum concentrations of glyburide were attained at a mean of 13 h after dosing, and mean apparent elimination half-life was approximately 7 h. Observed mean maximum plasma concentration was 31 ng/mL. At the glyburide dose administered there was no observable association between glyburide and glucose concentrations in blood. Discussion. Our data suggest that glyburide can be safely administered to dogs that are undergoing anesthesia, imaging and surgery for treatment of their acute spinal cord injury and can attain clinically-relevant serum concentrations without developing hazardous hypoglycemia. Serum glyburide concentrations achieved in this study suggest that a loading dose of 150 mcg/kg followed by repeat doses of 75 mcg/kg at 8-hourly intervals would lead to serum glyburide concentrations of 25-50 ng/mL within an acceptably short enough period after oral administration to be appropriate for a clinical trial in canine spinal cord injury. [ABSTRACT FROM AUTHOR]

Abstract: Aflatoxins are common contaminants of staple crops, such as corn and groundnuts, and a significant cause of concern for food safety and public health in developing countries. Aflatoxin B1 (AFB1) has been implicated in the etiology of acute and chronic disease in humans and animals, including growth stunting, liver cancer and death. Cost effective and culturally acceptable intervention strategies for the reduction of dietary AFB1 exposure are of critical need in populations at high risk for aflatoxicosis. Fermented gruels consisting of cornmeal are a common source for such exposure and are consumed by both children and adults in many countries with a history of frequent, high-level aflatoxin exposure. One proposed method to reduce aflatoxins in the diet is to include a selective enterosorbent, Uniform Particle Size NovaSil (UPSN), as a food additive in contaminated foods. For UPSN to be effective in this capacity, it must be stable in complex, acidic mixtures that are often exposed to heat during the process of fermented gruel preparation. Therefore, the objective of the present study was to test the ability of UPSN to sorb aflatoxin while common cooking conditions were applied. The influence of fermentation, heat treatment, acidity, and processing time were investigated with and without UPSN. Analyses were performed using the field-practical Vicam assay with HPLC verification of trends. Our findings demonstrated that UPSN significantly reduced aflatoxin levels (47–100%) in cornmeal, regardless of processing conditions. Upon comparison of each element tested, time appeared to be the primary factor influencing UPSN efficacy. The greatest decreases in AFB1 were reported in samples allowed to incubate (with or without fermentation) for 72h. This data suggests that addition of UPSN to staple corn ingredients likely to contain aflatoxins would be a sustainable approach to reduce exposure. [Copyright &y& Elsevier]

Abstract: The objective of this study was to evaluate the ability of NovaSil (NS) clay to sorb and mitigate the toxic effects of aflatoxin B1 (AFB1) in Nile tilapia (Oreochromis niloticus). Growth performance, targeted innate immunological function, intestinal microbial community and histology were evaluated after feeding tilapia diets with or without AFB1 and/or NS for 10weeks. Aflatoxin B1 at concentrations of 1.5 and 3.0ppm significantly (P <0.05) decreased weight gain, feed efficiency, hepatosomatic index and macrophage extracellular superoxide anion production in tilapia, regardless of NS addition to the diet. The overall results regarding the efficacy of NS were mixed; however, there was a trend (P =0.157) towards AFB1-toxicity prevention in regards to macrophage extracellular superoxide anion production. Additionally, when 0.5 and 1% NS was included in diets containing 1.5ppm AFB1, total histopathological score was lowered; however, this protective effect was not evident when fish were exposed to 3.0ppm AFB1. Denaturing gradient gel electrophoresis was performed to assess the effects of both AFB1 and NS on gut microbiota, but no significant differences were found among treatment groups. [Copyright &y& Elsevier]

OBJECTIVE To compare analgesic efficacy and fetal effects between transdermal administration of fentanyl and IM administration of buprenorphine in pregnant sheep. ANIMALS 12 healthy pregnant ewes. PROCEDURES Before study initiation, each ewe was confirmed pregnant with a single fetus between 113 and 117 days of gestation. Ewes were randomly assigned to receive buprenorphine (0.01 mg/kg, IM, q 8 h for 48 hours beginning I hour before anesthesia induction; n = 6) or fentanyl (a combination of transdermal fentanyl patches sufficient to deliver a dose of 2 mg of fentany l/kg/h applied between the dorsal borders of the scapulae 24 hours before anesthesia induction; 6). Ewes were anesthetized and underwent a surgical procedure to instrument the fetus with an arterial catheter and place a catheter in utero for collection of amniotic fluid samples. Physiologic variables and behavioral changes indicative of pain were assessed, and amniotic fluid and blood samples from ewes and fetuses were collected for determination of drug concentrations at predetermined times. RESULTS Both protocols provided acceptable postoperative analgesia with no adverse effects observed in the ewes or fetuses. Compared with the buprenorphine protocol, the fentanyl protocol induced more profound analgesia, decreased the requirement for isoflurane during surgery, and was associated with a shorter anesthesia recovery time. Fetal indices did not differ significantly between the 2 analgesic protocols. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both protocols provided acceptable analgesia. However, the fentanyl protocol was superior in regard to the extent of analgesia induced, inhalant-sparing effects, and anesthesia recovery time. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine Oxytetracycline concentrations in plasma and in fluid from Corynebacterium pseudotuberculosis (CPT)-inoculated tissue chambers (used as experimental abscess models) and uninoculated (control) tissue chambers in sheep after IM or local administration of the drug and to investigate whether CPI growth was reduced or eliminated by these treatments. ANIMALS 10 clinically normal female sheep. PROCEDURES Sterile tissue chambers were surgically implanted in both paralumbar fossae of each sheep; > 2 weeks later (day -6), I randomly selected chamber was inoculated with CPI, and the opposite chamber was injected with sterile growth medium. Sheep received Oxytetracycline IM (n = 5) or by percutaneous injection into CPT-inoculated (4) or uninoculated (I) chambers on day 0. Tissue fluid from each chamber and venous blood samples for plasma collection were obtained at predetermined times over 6 days for bacterial counts (tissue chambers) and analysis of Oxytetracycline concentrations (tissue chambers and plasma). Sheep were euthanized on day 6. Regional lymph nodes were collected bilaterally from each sheep for culture. RESULTS Measurable concentrations of Oxytetracycline were present in each chamber throughout the study, regardless of administration route or presence of CPT. No CPT growth was detected after the 48-hour time point in inoculated chambers injected with Oxytetracycline; however, CPT was isolated from all inoculated chambers throughout the study after IM drug administration. One regional lymph node (ipsilateral to a CPT-inoculated, oxytetracycline-injected chamber with no CPT growth after 48 hours) was culture positive for CPT. CONCLUSIONS AND CLINICAL RELEVANCE Intralesional administration of ox/tetracycline may eliminate growth of CPT locally, but complete elimination of the organism remains difficult. [ABSTRACT FROM AUTHOR]