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1.
J Small Anim Pract ; 64(1): 12-20, 2023 01.
Article in English | MEDLINE | ID: mdl-36089334

ABSTRACT

OBJECTIVES: This study aims to re-evaluate the low-dose dexamethasone suppression test 8-hour cortisol cut-point for the diagnosis of hypercortisolism in dogs using a solid-phase, competitive chemiluminescent enzyme immunoassay. MATERIALS AND METHODS: Twenty-seven client-owned dogs with naturally occurring hypercortisolism and 30 healthy control dogs were prospectively recruited. Performance of the low-dose dexamethasone suppression test was assessed using sensitivity, specificity and a receiver operating characteristic curve compared to a clinical diagnosis of hypercortisolism including response to treatment. RESULTS: Twenty-four dogs were diagnosed with pituitary-dependent hypercortisolism and three with adrenal-dependent hypercortisolism. In 30 healthy control dogs, 8-hour post-dexamethasone cortisol concentrations ranged from 5.5 to 39 nmol/L. A receiver operating characteristic curve curve constructed from the 8-hour post-dexamethasone cortisol concentrations of hypercortisolism and control dogs demonstrated that the most discriminatory cut-point was more than 39 nmol/L with sensitivity of 85.2% (95% confidence interval, 67.5% to 94.1%) and specificity of 100% (95% confidence interval, 88.7% to 100.0%) and an area under the curve of 0.963. CLINICAL SIGNIFICANCE: The optimal cut-point of more than 36 nmol/L proposed by this study is similar to the currently accepted 8-hour cortisol concentration cut-point for diagnosing hypercortisolism when using a solid-phase, competitive chemiluminescent enzyme immunoassay.


Subject(s)
Cushing Syndrome , Dog Diseases , Dogs , Animals , Hydrocortisone , Dexamethasone , Sensitivity and Specificity , Cushing Syndrome/veterinary , ROC Curve , Dog Diseases/diagnosis
2.
BMC Vet Res ; 17(1): 77, 2021 Feb 13.
Article in English | MEDLINE | ID: mdl-33581736

ABSTRACT

BACKGROUND: In humans, the drug metabolizing enzyme CYP2D6 is highly polymorphic resulting in substantial differences in the metabolism of drugs including anti-arrhythmics, neuroleptics, and opioids. The objective of this study was to phenotype a population of 100 horses from five different breeds and assess differences in the metabolic activity of the equine CYP2D6 homolog using codeine as a probe drug. Administration of a probe drug is a common method used for patient phenotyping in human medicine, whereby the ratio of parent drug to metabolite (metabolic ratio, MR) can be used to compare relative enzyme function between individuals. A single oral dose of codeine (0.6 mg/kg) was administered and plasma concentrations of codeine and its metabolites were determined using liquid chromatography mass spectrometry. The MR of codeine O-demethylation [(codeine)/(morphine + morphine-3-glucuronide + morphine-6-glucuronide)] was determined using the area under the plasma concentration-time curve extrapolated from time zero to infinity (AUC0-∞) for each analyte and used to group horses into predicted phenotypes (high-, moderate-, and low-MR). RESULTS: The MR of codeine O-demethylation ranged from 0.002 to 0.147 (median 0.018) among all horses. No significant difference in MR was observed between breeds, age, or sex. Of the 100 horses, 11 were classified as high-MR, 72 moderate-MR, and 17 low-MR. Codeine AUC0-∞ and O-demethylation MR were significantly different (p < 0.05) between all three groups. The mean ± SD MR was 0.089 ± 0.027, 0.022 ± 0.011, and 0.0095 ± 0.001 for high-, moderate-, and low-MR groups, respectively. The AUC for the morphine metabolites morphine-3-glucuronide and morphine-6-glucuronide were significantly different between high-and low-MR groups (p < 0.004 and p < 0.006). CONCLUSIONS: The MR calculated from plasma following codeine administration allowed for classification of horses into metabolic phenotypes within a large population. The range of codeine metabolism observed among horses suggests the presence of genetic polymorphisms in CYP2D82 of which codeine is a known substrate. Additional studies including CYP2D82 genotyping of high- and low-MR individuals are necessary to determine the presence of CYP2D polymorphisms and their functional implications with respect to the metabolism of therapeutics.


Subject(s)
Codeine/metabolism , Codeine/pharmacokinetics , Cytochrome P-450 CYP2D6/metabolism , Animals , Codeine/analogs & derivatives , Codeine/blood , Cytochrome P-450 CYP2D6/genetics , Female , Horses , Male , Morphine Derivatives/metabolism , Phenotype , Polymorphism, Genetic
4.
Theriogenology ; 134: 83-89, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31153092

ABSTRACT

In equids, it is common to inject lidocaine into the testicles at the time of routine castration to provide analgesia. The effects of lidocaine on equine sperm have not been evaluated in vitro or on epididymal sperm collected following castration. The aims of this study were to determine effects of clinically relevant doses of lidocaine on equine spermatozoa in vitro using freshly collected semen and to compare the characteristics of epididymal spermatozoa after routine castration with or without intra-testicular lidocaine administration. We hypothesized that increasing concentrations of lidocaine would decrease total motility (TM), progressive motility (PM), velocity of the average path (VAP), velocity of the curved line (VCL), linearity (LIN), normal morphology (M) and membrane integrity (MI). We also hypothesized that injection of intra-testicular lidocaine would decrease TM, PM, VAP, VCL, LIN, M, and MI following routine castration, epididymal flushing and cryopreservation. In experiment 1, sperm was collected from four stallions and mixed with lidocaine at concentrations of 1 µg/ml, 10 µg/ml, 100 µg/ml, 1,000 µg/ml and 10,000 µg/ml. M and MI were compared to the control sample at 0 and 48 h. Motility parameters were analyzed at 0, 2, 4, 6, 24, and 48 h. In experiment 2, 12 stallions were castrated under general anesthesia. One testicle was removed without the use of intra-testicular lidocaine and the other testicle was removed 10 min after injection of 10 ml of 2% lidocaine. Results: In experiment 1, fresh sperm showed no significant difference (p < 0.05) compared to control at either 1 µg/ml or 10 µg/ml concentrations of lidocaine. There were significant decreases in PM, VAP, VCL, and LIN at concentrations of 100µg/ml-10,000 µg/ml and for TM at lidocaine concentrations of 1,000-10,000 µg/ml compared to control. Morphology did not change at any lidocaine concentration. Membrane integrity decreased significantly at 10,000 µg/ml lidocaine. In the second experiment 1.03 ±â€¯0.42 µg/ml lidocaine was detected in the epididymal flush of stallions treated with lidocaine. There were no significant differences in any measured parameters between the control and the lidocaine treated testicles. Intra-testicular lidocaine injection at the time of castration did not affect any measured parameters after epididymal flush. Lidocaine concentrations higher than 100 µg/ml in-vitro resulted in decreased motility parameters of the spermatozoa independent of exposure time.


Subject(s)
Anesthetics, Local/adverse effects , Lidocaine/adverse effects , Semen Analysis/veterinary , Semen/drug effects , Spermatozoa/drug effects , Anesthetics, Local/therapeutic use , Animals , Cryopreservation/veterinary , Epididymis , Horses , Lidocaine/therapeutic use , Male , Orchiectomy , Semen Preservation/veterinary , Sperm Motility/drug effects , Spermatozoa/physiology , Testis/drug effects
5.
J Comp Pathol ; 167: 60-72, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30898300

ABSTRACT

Skull specimens from 836 kit foxes (Vulpes macrotis) were examined macroscopically according to predefined criteria; 559 specimens were included in this study. The study group consisted of 248 (44.4%) females, 267 (47.8%) males and 44 (7.9%) specimens of unknown sex; 128 (22.9%) skulls were from young adults and 431 (77.1%) were from adults. Of the 23,478 possible teeth, 21,883 teeth (93.2%) were present for examination, 45 (1.9%) were absent congenitally, 405 (1.7%) were acquired losses and 1,145 (4.9%) were missing artefactually. No persistent deciduous teeth were observed. Eight (0.04%) supernumerary teeth were found in seven (1.3%) specimens and 13 (0.06%) teeth from 12 (2.1%) specimens were malformed. Root number variation was present in 20.3% (403/1,984) of the present maxillary and mandibular first premolar teeth. Eleven (2.0%) foxes had lesions consistent with enamel hypoplasia and 77 (13.8%) had fenestrations in the maxillary alveolar bone. Periodontitis and attrition/abrasion affected the majority of foxes (71.6% and 90.5%, respectively). Nine-hundred and fifty-eight (4.4%) teeth were fractured, a large proportion (41.8%) of which were characterized as complicated crown fractures. Sixty-six periapical lesions from 52 (9.3%) skulls were found. A considerable portion of foxes (5.9%) showed evidence of low-grade temporomandibular joint osteoarthritis. Overall, kit foxes share dental pathology similar to that of the grey fox (Urocyon cinereoargenteus).


Subject(s)
Foxes , Temporomandibular Joint Disorders/veterinary , Tooth Diseases/veterinary , Tooth Injuries/veterinary , Animals , Female , Male
6.
Equine Vet J ; 51(2): 238-245, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30080272

ABSTRACT

BACKGROUND: Flumetasone is a potent corticosteroid reportedly used in horses to decrease inflammation associated with strenuous exercise. There are currently no reports describing the use of this drug in horses. OBJECTIVES: To describe the pharmacokinetics and effects on cortisol and eicosanoid concentrations, following administration of flumetasone to exercised horses. STUDY DESIGN: Parallel design. METHODS: Twelve exercised horses received a single i.v. administration of 5 mg of flumetasone. Blood and urine samples were collected before and for 72 h post-drug administration for determination of flumetasone and cortisol concentrations. Whole blood samples were collected at various time and challenged with lipopolysaccharide, calcium ionophore or methanol to induce ex vivo synthesis of eicosanoids. Concentrations of flumetasone, cortisol and eicosanoids were measured using LC-MS/MS and pharmacokinetic/pharmacodynamic analysis performed. RESULTS: Flumetasone was detected for 23.5 ± 1.73 h in blood. The volume of distribution at steady state, systemic clearance and elimination half-life was 5.90 ± 0.200 L/kg, 30.7 ± 0.166 mL/min/kg and 4.84 ± 0.83 h respectively. Cortisol concentrations were still suppressed at last time point collected (72 h). For cortisol, Kin , Kout and the t1/2out were 30.3 ± 1.56 ng/mL × h, 0.331 ± 0.02 1/h and 2.1 h respectively. Stimulation with lipopolysaccharide resulted in a decrease in TXB2 , PGF2 , LTB4 , 15-HETE and 5-HETE for up to 72 h and PGE2 for 24 h post-flumetasone administration. Stimulation of whole blood with calcium ionophore resulted in a decrease in LTB4 for up to 6 h and 15-HETE at 8 h. MAIN LIMITATIONS: Lack of sample collection for determination of biomarker concentrations beyond 72 h and the use of a single sample for determination of baseline cortisol concentrations. CONCLUSIONS: Flumetasone is rapidly cleared from blood following administration to horses. It is a potent anti-inflammatory with prolonged effects on production of cortisol and other inflammatory mediators.


Subject(s)
Flumethasone/pharmacokinetics , Horses/physiology , Hydrocortisone/blood , Inflammation/veterinary , Animals , Area Under Curve , Biomarkers , Cytokines/genetics , Cytokines/metabolism , Flumethasone/blood , Flumethasone/pharmacology , Gene Expression Regulation/drug effects , Glucocorticoids/blood , Glucocorticoids/pharmacokinetics , Half-Life , Horses/blood , Inflammation/metabolism
7.
Vet J ; 242: 59-66, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30503546

ABSTRACT

Several ultrasonic and Fourier-domain optical coherence tomography (FD-OCT) pachymeters are used to measure corneal thickness in canine patients and research subjects. This study assessed the reliability of and consistency between two ultrasonic pachymetry (USP) devices, Pachette 3 and Accupach VI, as well as automated and manual measurements obtained using FD-OCT in dogs with and without corneal disease. Corneal thickness measurements were compiled from 108 dogs and analyzed using mixed effects linear regression, with Bonferonni adjustments for post-hoc comparisons, to determine the effects of age, weight and disease state. Data are presented as predicted mean±standard error. Canine corneal disease can result in marked increases in thickness that frequently exceed the upper limits of measurement of some pachymetry devices developed for human use. In this study, the corneas of dogs with endothelial disease or injury frequently exceeded the upper limits of quantitation of 999 and 800µm for the Accupach VI and automated FD-OCT pachymeters, respectively. Using values <800µm, the Pachette 3 generated significantly greater values for central corneal thickness (CCT) than the Accupach VI, manual FD-OCT and automated FD-OCT at 625±7.0, 615±7.2, 613±7.2, and 606±7.4µm respectively (P<0.001). Of the two devices where measurements >1000µm were obtained, manual FD-OCT demonstrated less variability than the Pachette 3. Corneal thickness increased linearly with age and weight with an increase of 6.9±1.8µm/year and 1.6±0.8µm/kg body weight (P<0.005 and P=0.038, respectively).


Subject(s)
Cornea/anatomy & histology , Corneal Diseases/veterinary , Corneal Pachymetry/veterinary , Dog Diseases/diagnostic imaging , Dogs/anatomy & histology , Tomography, Optical Coherence/veterinary , Animals , Case-Control Studies , Corneal Diseases/diagnostic imaging , Female , Male , Predictive Value of Tests
8.
J Vet Intern Med ; 32(5): 1731-1739, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30084236

ABSTRACT

BACKGROUND: Neuroglycopenia refers to a shortage of glucose in the brain resulting in neuronal dysfunction and death if left untreated. Presumed neuroglycopenia has not been described in horses. OBJECTIVE: To report neurological signs in horses with presumed neuroglycopenia as the result of severe hypoglycemia. ANIMALS: Ninety horses (hours to 28 years of age) diagnosed with hypoglycemia (blood glucose concentration < 75 mg/dL [< 4.2 mmol/L]). METHODS: Retrospective study. Electronic medical records were searched. Signalment, history, complaint, clinical signs, laboratory findings including CSF analysis, electroencephalogram, clinical or definitive diagnosis, and outcome were recorded. Kruskal-Wallis analysis of variance and logistic regression were used to investigate association between blood glucose concentration and data extracted. Statistical significance was set at P < 0.05. RESULTS: Thirty-eight and 52 horses had mild (50-74 mg/dL [2.8-4.1 mmol/L]), and severe hypoglycemia (< 50 mg/dL [< 2.8 mmol/L]), respectively. Most common causes of hypoglycemia included liver and gastrointestinal (40%) disease, sepsis (33%), neoplasia (7%), and insulin-induced (4%). Most common neurologic deficits included obtundation (100%), seizures (42%), and disorientation (22%). CSF-glucose was severely low (mean 2.5 mg/dL [0.1 mmol/L], median 0 mg/dL). Paroxysmal discharges in support of seizures were identified in the occipital (visual) and parietal (closest to temporal-auditory) cortical regions upon EEG examination (8/8 horses). CONCLUSIONS AND CLINICAL IMPORTANCE: Neuroglycopenia is presumed to occur in horses as the result of severe hypoglycemia. Subclinical seizures, and intermittent blindness and deafness of cortical origin can occur. Severe altered state of consciousness and seizures can be observed at a blood glucose cut-off value of < 42 mg/dL (< 2.3 mmol/L).


Subject(s)
Brain/metabolism , Central Nervous System Diseases/veterinary , Glucose/metabolism , Horse Diseases/etiology , Hypoglycemia/veterinary , Aging , Animals , Animals, Newborn , Blood Glucose , Central Nervous System Diseases/etiology , Female , Horses , Hypoglycemia/complications , Male , Retrospective Studies
9.
J Comp Pathol ; 160: 56-70, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29729722

ABSTRACT

Skulls from 392 grey wolves (Canis lupus) were examined macroscopically according to predefined criteria. Two hundred and seven skulls were included in this study, comprised of 124 young adults (59.9%) and 83 adults (40.1%); of these, 65 (31.4%) specimens were from male wolves and 104 (50.3%) were from females, with 38 (18.4%) of unknown sex. Out of 8,694 possible teeth, 8,339 (95.9%) were present for evaluation. Fifty-five teeth (15.5%) were absent congenitally, 30 (8.5%) were lost during life and 270 (76.1%) were lost artefactually post mortem. Skeletal or dental malocclusion was present in 37 specimens (17.9%), with level bite being the most commonly encountered malocclusion. Enamel hypoplasia was present in five skulls (2.4%), affecting eight teeth (0.1%) in total. An abnormal number of roots was found on 23 teeth (0.3%) on 13 skulls (6.3%). Persistent deciduous teeth occurred in two (1.0%) specimens, affecting one (0.01%) tooth each. Fenestration or dehiscence was found associated with 203 teeth (2.4%) in 72 skulls (34.8%). Periodontitis was noted on 115 skulls (55.6%) and 1,000 teeth (11.5%), affecting significantly more adults (n = 63, 75.0%) than young adults (n = 52, 41.9%; P <0.0001). One hundred and sixty-one skulls (77.8%) showed signs of endodontal disease, including attrition or abrasion on 144 skulls (69.6%) and 2,522 teeth (30.2%) and 424 fractured teeth (5.1%) on 103 skulls (49.8%). Both lesions affected significantly more adults than young adults. Overt periapical disease was associated with six teeth (0.1%) distributed across five skulls (2.4%). A carious lesion was present on one tooth (0.01%) of one specimen (0.5%). Lesions consistent with temporomandibular joint (TMJ) osteoarthritis were found in 24 specimens (11.6%), affecting 38 joints (9.2%). Trauma to the skull, such as bite marks, bullet holes or blunt trauma, was noted in 44 skulls (21.2%). The grey wolf and the domestic dog (Canis lupus familiaris) share common dental diseases; however, the proportion and severity may vary. Although the clinical significance of dental and TMJ pathology in the grey wolf remains unknown, based on the impact of these disorders on the domestic dog, the occurrence and severity of these lesions are likely to play an important role in the morbidity and mortality of this wild canid species.


Subject(s)
Stomatognathic Diseases/veterinary , Temporomandibular Joint Disorders/veterinary , Wolves , Animals , Female , Male , Temporomandibular Joint/pathology , Tooth/pathology
10.
J Vet Pharmacol Ther ; 41(4): 522-535, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29457257

ABSTRACT

Acepromazine is a tranquilizer used commonly in equine medicine. This study describes serum and urine concentrations and the pharmacokinetics and pharmacodynamics of acepromazine following intravenous, oral, and sublingual (SL) administration. Fifteen exercised adult Thoroughbred horses received a single intravenous, oral, and SL dose of 0.09 mg/kg of acepromazine. Blood and urine samples were collected at time 0 and at various times for up to 72 hr and analyzed for acepromazine and its two major metabolites (2-(1-hydroxyethyl) promazine and 2-(1-hydroxyethyl) promazine sulfoxide) using liquid chromatography-tandem mass spectrometry. Acepromazine was also incubated in vitro with whole equine blood and serum concentrations of the parent drug and metabolites determined. Acepromazine was quantitated for 24 hr following intravenous administration and 72 hr following oral and SL administration. Results of in vitro incubations with whole blood suggest additional metabolism by RBCs. The mean ± SEM elimination half-life was 5.16 ± 0.450, 8.58 ± 2.23, and 6.70 ± 2.62 hr following intravenous, oral, and SL administration, respectively. No adverse effects were noted and horses appeared sedate as noted by a decrease in chin-to-ground distance within 5 (i.v.) or 15 (p.o. and SL) minutes postadministration. The duration of sedation lasted 2 hr. Changes in heart rate were minimal.


Subject(s)
Acepromazine/pharmacokinetics , Hypnotics and Sedatives/pharmacokinetics , Acepromazine/administration & dosage , Acepromazine/blood , Acepromazine/pharmacology , Administration, Oral , Administration, Sublingual , Animals , Chromatography, Liquid/veterinary , Female , Horses/blood , Horses/metabolism , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/blood , Hypnotics and Sedatives/pharmacology , Infusions, Intravenous/veterinary , Male , Physical Conditioning, Animal , Tandem Mass Spectrometry/veterinary
11.
J Comp Pathol ; 158: 39-50, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29422314

ABSTRACT

Museum specimens from 637 grey foxes (Urocyon cinereoargenteus) were examined macroscopically according to predefined criteria. Of the 637 specimens, 569 were included for further examination. The study population included more males (n = 261, 45.9%) than females (n = 196, 34.4%) and animals of unknown sex (n = 112, 19.7%). Additionally, 481 (84.5%) adults, 67 (11.8%) young adults and 21 (3.7%) individuals of unknown age comprised the study population, with juveniles and neonates excluded. The number of teeth present for examination was 23,066 (96.5%) with 624 (2.6%) absent artefactually, 15 (0.06%) absent congenitally and 193 (0.8%) lost ante mortem through acquired tooth loss. No persistent deciduous teeth or temporomandibular joint osteoarthritis were found in any of the specimens. Ten supernumerary teeth from nine (1.6%) specimens were encountered. Teeth with extra roots were found in 61 individuals (10.7%), with 0.4% of all teeth affected. Of the alveoli examined, 1,529 (6.4%) displayed bony changes suggestive of periodontitis, with 276 (48.7%) of individuals affected. Significantly more adults were affected by bony changes associated with stage 3 periodontitis than young adults. All specimens displaying stage 4 periodontitis were adults. Fractures affected 446 (78.4%) of the specimens examined and 3,554 (15.4%) of teeth present. Almost half (n = 10,856, 47.1%) of the teeth available for examination and most specimens (n = 487, 85.6%) displayed some degree of attrition or abrasion. Two individuals (0.4%) exhibited periapical lesions. Traumatic skull injuries affected 56 (9.8%) specimens. Characterizing the dental pathology in the grey fox provides key insight into the ecology of the species and factors contributing to fitness.


Subject(s)
Foxes , Tooth Diseases/veterinary , Animals , Female , Male
12.
Equine Vet J ; 50(3): 350-355, 2018 May.
Article in English | MEDLINE | ID: mdl-28963734

ABSTRACT

BACKGROUND: Due to the high prevalence of EIPH in racehorses and its potential impact on the horse's health, furosemide administration is permitted up to 4-h prior to post time in most North American racing jurisdictions. Anecdotal reports suggest that administration of furosemide 24-h prior to strenuous exercise may be equally effective in decreasing the severity of EIPH. OBJECTIVES: To 1) compare the efficacy of furosemide in reducing the presence and severity of EIPH when administered 4- or 24-h prior to strenuous exercise 2) characterise electrolyte and blood parameters following administration of furosemide at 4- and 24-h prior to exercise. STUDY DESIGN: 3-way crossover. METHODS: Fifteen Thoroughbred racehorses received 5 mL of 0.9% NaCl or 250 mg of furosemide either 4- or 24-h prior to a 5-furlong simulated race. Blood samples were collected prior to and post-run for determination of furosemide, lactate, haemoglobin and electrolyte concentrations. One-hour post-race, an endoscopic exam and bronchoalveolar lavage (BAL) were performed. Horses were assigned an EIPH score based on predetermined criteria and the number of red blood cells in BAL fluid was determined. RESULTS: Endoscopic EIPH scores were lower in the 4-h vs. the 24-h (P = 0.03) furosemide groups. RBC counts in BAL fluid were lower in the 4-h furosemide vs. saline treatment groups (P = 0.01) but no difference was noted between the saline and 24-h furosemide groups (P = 0.3), nor between the 4- and 24-h groups (P = 0.5). MAIN LIMITATIONS: Small sample size and large range of running times for the 5-furlong work. CONCLUSIONS: While none of the treatments prevented EIPH, endoscopic scores and RBC counts in BAL fluid support the efficacy of furosemide in reducing the severity of EIPH. Endoscopic scores were lower in the 4-h furosemide group compared with 24-h administration. Red blood cell counts were lower in the 4-h furosemide group compared with saline treatment.


Subject(s)
Furosemide/pharmacology , Hemorrhage/veterinary , Horse Diseases/etiology , Lung Diseases/veterinary , Physical Conditioning, Animal/adverse effects , Animals , Bronchoalveolar Lavage Fluid , Cross-Over Studies , Diuretics/pharmacology , Female , Hemorrhage/prevention & control , Horse Diseases/prevention & control , Horses , Lung Diseases/etiology , Lung Diseases/prevention & control , Male , Physical Exertion , Running
13.
J Vet Pharmacol Ther ; 41(2): 224-229, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29057472

ABSTRACT

Furosemide is a diuretic agent used commonly in racehorses to attenuate the bleeding associated with exercise-induced pulmonary hemorrhage (EIPH). The current study describes serum and urine concentrations and the pharmacokinetics of furosemide following administration at 4 and 24 hrs prior to maximal exercise. Eight exercised adult Thoroughbred horses received a single IV administration of 250 mg of furosemide at 4 and 24 hrs prior to maximal exercise on a high-speed treadmill. Blood and urine samples were collected at time 0 and at various times for up to 72 hrs and furosemide concentrations determined using liquid chromatography-tandem mass spectrometry. Serum furosemide concentrations remained above the LOQ (0.05 ng/ml) for 36 hrs in 3/8 and 1/8 horses in the 4- and 24-hrs groups, respectively. Serum concentration data were best fit by a two-compartment model. There was not a significant difference in the volume of distribution at steady-state (0.594 ± 0.178 [4 hrs] and 0.648 ± 0.147 [24 hrs] L/kg) or systemic clearance (0.541 ± 0.094 [4 hrs] and 0.617 ± 0.114 [24 hrs] L/hrs/kg) between horses that were exercised at 4- and 24 hrs postdrug administration. The mean ± SD elimination half-life was 3.12 ± 0.387 and 3.23 ± 0.407 hrs following administration at 4 and 24 hrs prior to exercise, respectively.


Subject(s)
Diuretics/pharmacokinetics , Furosemide/pharmacokinetics , Physical Conditioning, Animal/adverse effects , Animals , Diuretics/administration & dosage , Diuretics/blood , Diuretics/urine , Female , Furosemide/administration & dosage , Furosemide/blood , Furosemide/urine , Hemorrhage/etiology , Hemorrhage/prevention & control , Hemorrhage/veterinary , Horse Diseases/etiology , Horse Diseases/prevention & control , Horses/blood , Horses/metabolism , Horses/urine , Lung Diseases/etiology , Lung Diseases/prevention & control , Lung Diseases/veterinary , Male , Physical Conditioning, Animal/physiology
14.
Equine Vet J ; 50(4): 504-512, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29044706

ABSTRACT

BACKGROUND: Intra-articular use of corticosteroids is commonplace in performance horses. Isoflupredone acetate (IPA) is one of four Food and Drug Administration approved corticosteroids for intra-articular use in horses. The lack of published reports describing the efficacy and duration of effects of this drug warrant further study. OBJECTIVES: To assess the effects of intra-articular administration of IPA on the expression of selected anti- and pro-inflammatory and structural matrix genes following intra-articular administration to exercised Thoroughbred horses and to correlate these effects with drug concentrations. STUDY DESIGN: Block design in vivo experiment. METHODS: Twelve exercised horses received either a single intra-articular administration of 8 mg of IPA or 0.9% saline solution. Synovial fluid samples were collected prior to and up to 42 days post drug administration from the treated joints. Microarray and qRT-PCR analysis were used to assess changes in expression levels of various inflammatory and structural genes post drug administration. RESULTS: On microarray analysis, 855, 23,358 and 26,411 genes had a measurable fold change (increase or decrease in expression levels) when comparing baseline samples to 24 h, baseline samples to day 7 and 24 h samples to day 7, respectively. Of the genes selected for further study by qRT-PCR analysis, expression of ANXA-1 (lipocortin) was significantly increased and IL23A and MMP1 and MMP9 significantly decreased following IPA administration. Expression levels of collagen genes were not significantly different from baseline. MAIN LIMITATIONS: Limitations include the use of a noninflammatory model as results may differ in the presence of an acute inflammatory insult and the inability to measure protein concentrations of inflammatory mediators due to limited synovial fluid sample volume. CONCLUSIONS: Expression relative to baseline, for both inflammatory and matrix genes for up to 42 days post IPA administration, suggests a prolonged effect relative to detection time in both plasma and synovial fluid.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Fluprednisolone/analogs & derivatives , Gene Expression Regulation/drug effects , Inflammation/metabolism , Physical Conditioning, Animal , Animals , Female , Fluprednisolone/pharmacology , Horse Diseases , Horses , Injections, Intra-Articular/veterinary , Male , RNA, Messenger , Synovial Fluid/chemistry
15.
Vet J ; 227: 15-22, 2017 Sep.
Article in English | MEDLINE | ID: mdl-29031325

ABSTRACT

Animal shelters struggle to function at their 'right size' in terms of physical, staffing and outcome capacity, especially with seasonal fluctuations in cat intake. To address this, a Capacity for Care (C4C) management model was devised to balance health and welfare requirements of all animals while maintaining or improving goals for positive outcomes, such as adoption or transfer. In this observational study of three shelters, applying the C4C management system gave each organization an optimal average daily shelter cat population target (to be achieved through proactive length of stay management) and helped each shelter to increase the size of their feline housing units. Pre- and post-C4C implementation data were evaluated to determine impact on average monthly isolation ward populations and cat outcomes such as adoptions and shelter deaths (euthanasia/died). Improved outcomes including increased adoption probability, decreased shelter death probability and fewer cats requiring infectious disease isolation were seen after C4C institution. Results suggest that implementation of this management model could help other shelters achieve similar results.


Subject(s)
Animal Welfare , Cats , Housing, Animal , Animal Welfare/organization & administration , Animals , Housing, Animal/organization & administration , Housing, Animal/standards , Models, Organizational , Pets
16.
Vet J ; 227: 23-29, 2017 Sep.
Article in English | MEDLINE | ID: mdl-29031326

ABSTRACT

Few studies have evaluated the effects of age and illness on serum triglyceride concentrations in neonatal foals. The objectives of this study were to evaluate triglyceride concentrations in neonatal foals and their dams through serial measurement immediately postpartum and at 1-2 days and 10-12 days of age, as well as to measure them in sick foals. Serially measured serum triglycerides in seven healthy foals varied with age. Median (range) triglyceride concentrations were 28mg/dL (12-50mg/dL), 89mg/dL (51-264mg/dL), and 60mg/dL (28-135mg/dL) immediately postpartum, at 1-2 days of age, and 10-12 days of age, respectively (P<0.001). Triglyceride concentrations varied hourly by up to 117mg/dL in individual foals. The dams had lower triglycerides (median, 20mg/dL; range, 12-49mg/dL) than the foals, once foals were >24h old. Sick foals <24h old had lower triglycerides than sick foals aged 1-7 days (median, 41mg/dL [range, 16-116]; median, 110mg/dL [range, 24-379mg/dL]; P<0.001). Age and triglyceride concentration showed a non-linear association independent of foal health status (P=0.01). Sick foals with positive bacterial cultures had higher triglycerides than those with negative cultures (median, 111mg/dL [range, 10-379mg/dL] and median 53mg/dL [range, 17-271mg/dL], respectively; P=0.033). Nonsurvivors had higher triglycerides than survivors (median, 116mg/dL [range, 41-379mg/dL] and median, 55mg/dL [range, 10-311mg/dL], respectively; P=0.04). In conclusion, triglycerides were highest in healthy neonatal foals aged 1-2 days, and in nonsurviving sick foals and those with positive bacterial cultures. Age was associated with triglyceride concentration regardless of health status.


Subject(s)
Animals, Newborn/blood , Horse Diseases/blood , Horses/blood , Triglycerides/blood , Aging/blood , Animals , Female , Reference Values
17.
J Comp Pathol ; 157(2-3): 90-102, 2017.
Article in English | MEDLINE | ID: mdl-28942310

ABSTRACT

Museum specimens (maxillae and mandibles) from 393 North American brown bears (Ursus arctos) from Alaska were examined macroscopically according to predefined criteria and 204 specimens were included in this study. The specimens were acquired between 1905 and 2012. There were 99 specimens (48.5%) from male animals, 87 (42.7%) from female animals and 18 (8.8%) from animals of unknown sex. The ages of the animals ranged from neonate to adult, with 92 adults (45.1%) and 112 young adults (54.9%) included and neonates/juveniles excluded from the study. The number of teeth available for examination was 6,525 (76.2%); 8.6% of teeth were absent artefactually, 0.8% were deemed absent due to acquired tooth loss and 14.5% were absent congenitally. None of the brown bears had supernumerary teeth, persistent deciduous teeth or abnormally formed crowns. Only four of the specimens in the present population were affected by enamel hypoplasia and one specimen contained two mandibular fourth premolar teeth with one root instead of two. All 204 specimens displayed at least some degree of attrition/abrasion, affecting 63% of all teeth, ranging from mild wear of the enamel to deep abrasion associated with pulp exposure. Ten-times more adult than young adult specimens had abrasion causing pulp exposure, while more young adults showed mild attrition/abrasion. Dental fractures were noted in one-third of brown bears and in 3.0% of the total number of present teeth. More adult brown bears had dental fractures than young adults. There were 11 specimens (5.4%) that displayed overt periapical disease, affecting a total of 20 dental alveoli (0.22%), with adults significantly more affected than young adults. Some degree of periodontitis was seen in 145 specimens (71.1%), affecting 13.6% of all dental alveoli. Nearly one-third (29.9%) of skulls displayed skeletal and/or dental malocclusion, most commonly a level bite. Lesions consistent with temporomandibular joint (TMJ) osteoarthritis were found in 27 specimens (13.2%). Caries lesions were discovered in four specimens (2.0%), affecting eight teeth in total. Although the clinical significance of dental and TMJ pathology in the brown bear remains elusive, the occurrence and severity of some of these lesions may play an important role in the morbidity of this species.


Subject(s)
Temporomandibular Joint Disorders/veterinary , Tooth Diseases/veterinary , Ursidae , Animals , Female , Male
18.
Equine Vet J ; 49(6): 810-814, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28470857

ABSTRACT

BACKGROUND: Brimonidine is an α2 -adrenergic agonist that decreases aqueous humour production and may increase uveoscleral outflow. It has not been evaluated in normal or glaucomatous equine eyes. OBJECTIVES: To evaluate the efficacy and safety of brimonidine in lowering intraocular pressure (IOP), alone and in conjunction with timolol, as a treatment for equine glaucoma by comparing IOP in normal equine eyes treated with brimonidine and brimonidine-timolol, respectively, with IOP in control eyes. STUDY DESIGN: A balanced crossover design with 16 horses receiving one of two treatments, brimonidine and brimonidine-timolol, during each of two 10-day study phases, was used. Four horses were randomly assigned to each of four combinations of treated eye (right or left) and drug order within the two 10-day study phases (brimonidine first or brimonidine-timolol first). METHODS: Pupil size and conjunctival hyperaemia were assessed twice per day and IOP was measured three times per day using rebound tonometry in both eyes of 16 normal horses throughout two 10-day study periods (brimonidine and brimonidine-timolol) separated by an 18-day washout period. One eye of each horse was treated with brimonidine or brimonidine-timolol and the opposite eye was treated with balanced salt solution (BSS). RESULTS: There were no adverse effects and no significant changes in pupil size in normal equine eyes treated with brimonidine or brimonidine-timolol. Average IOP in normal equine eyes treated with brimonidine (25.6 mmHg) was statistically higher than in eyes treated with brimonidine-timolol (24.6 mmHg) or BSS (24.5 mmHg). However, IOP differences were of ≤1 mmHg and thus not clinically important. MAIN LIMITATIONS: Horses with normal eyes may not be as sensitive to the IOP-lowering effects of treatment as horses with glaucoma. CONCLUSIONS: Brimonidine and brimonidine-timolol are well tolerated in normal horses but do not decrease IOP.


Subject(s)
Brimonidine Tartrate, Timolol Maleate Drug Combination/pharmacology , Brimonidine Tartrate/pharmacology , Horses/physiology , Intraocular Pressure/drug effects , Pupil/drug effects , Aging , Animals , Brimonidine Tartrate/administration & dosage , Circadian Rhythm , Female , Male
19.
Equine Vet J ; 49(6): 770-775, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28517110

ABSTRACT

BACKGROUND: Temporohyoid osteoarthropathy (THO) is a cause of neurological disease in horses that is characterised by facial and vestibulocochlear nerve deficits. Studies reporting and comparing survival following medical or surgical treatment of THO are lacking. OBJECTIVES: To compare survival and prognosis in horses with THO treated medically or surgically, and to report surgical complications. STUDY DESIGN: Retrospective study. METHODS: The medical records of horses diagnosed with THO were retrieved, and data on signalment, clinical signs and duration, corneal ulceration and bilateral occurrence were recorded. Neurological severity was graded according to clinical signs. Preoperative radiographic and endoscopic images were graded according to the severity of changes. Factors potentially affecting survival and treatment were compared using Cox proportional hazards regression. RESULTS: A total of 77 horses were identified as having THO during the period 1990-2014. Of these, 25 horses underwent ceratohyoid ostectomy (CHO) and eight underwent partial stylohyoid ostectomy (PSHO). Thirteen of 20, one of 25 and one of eight horses treated by medical therapy, CHO and PSHO, respectively, died or were subjected to euthanasia as a consequence of THO. Compared with CHO, medical therapy was significantly associated with nonsurvival, but there were no significant differences in survival between horses undergoing PSHO and medical therapy. The duration of clinical signs, and neurological, radiographic and endoscopic grades were not associated with survival of THO. However, the age of the horse was significantly associated with poorer survival. Survival time was significantly shorter in the medical therapy group compared with the two surgical groups combined, but did not differ significantly between the two surgical groups. No significant difference between groups was seen in the incidence of surgical complications (33.3% in the PSHO and 22.2% in the CHO group). MAIN LIMITATIONS: This was a nonrandomised study of treatment effects on survival and included a low number of cases. CONCLUSIONS: The survival prognosis in horses with THO is good to excellent in those submitted to surgical intervention, and fair in those treated with medical therapy alone.


Subject(s)
Horse Diseases/therapy , Joint Diseases/veterinary , Osteoarthritis/veterinary , Animals , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Female , Horses , Jaw/pathology , Joint Diseases/therapy , Male , Osteoarthritis/drug therapy , Osteoarthritis/surgery , Retrospective Studies
20.
J Vet Intern Med ; 31(3): 730-733, 2017 May.
Article in English | MEDLINE | ID: mdl-28407319

ABSTRACT

BACKGROUND: Standard protocols for adrenocorticotropic hormone (ACTH) stimulation testing (ACTHst) often involve intravenous (IV) injection of corticotropin. ACTH might be unintentionally injected into the perivascular (PV) space. OBJECTIVE: To compare stimulation test results after IV and PV injections of ACTH. ANIMALS: Twenty privately owned dogs were studied: 10 healthy and 10 with trilostane-treated naturally occurring hyperadrenocorticism (HAC). METHODS: Prospective study. Each of 20 dogs underwent 2 ACTHst not <4 nor more than 14 days apart. Five healthy and 5 HAC dogs had an IV ACTHst first and PV second; 5 healthy and 5 HAC dogs had a PV ACTHst first and IV second. Blood samples for measurement of serum cortisol concentration were collected before and 1 hour after ACTH administration. RESULTS: No significant difference in results was demonstrated when comparing serum cortisol concentrations after IV and PV ACTH administration in all 20 dogs (median µg/dL; interval µg/dL: 8.2; 1.4-17.4 versus 7.8; 0.9-16.9; P = .23). No significant difference in results was demonstrated when comparing serum cortisol concentrations after IV and PV ACTH administration in the 10 healthy dogs (median µg/dL; interval µg/dL: 10.9; 7.3-17.4 versus 10.6; 7.1-16.9; P = .54) or in the 10 HAC dogs (median µg/dL; interval µg/dL: 6.3; 1.4-8.6 versus 5.2; 0.9-8.7; P = .061). CONCLUSIONS AND CLINICAL IMPORTANCE: Perivascular administration of ACTH does not significantly alter stimulation test results in healthy dogs or in dogs with HAC undergoing therapy with trilostane.


Subject(s)
Adrenocortical Hyperfunction/veterinary , Adrenocorticotropic Hormone/administration & dosage , Dog Diseases/diagnosis , Hydrocortisone/blood , Adrenocortical Hyperfunction/diagnosis , Animals , Case-Control Studies , Dog Diseases/blood , Dogs , Female , Injections, Intravenous/veterinary , Injections, Subcutaneous/veterinary , Male
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