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BackgroundIn 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).ResultsThe 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

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).

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 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

BackgroundNeuroglycopenia 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.ObjectiveTo report neurological signs in horses with presumed neuroglycopenia as the result of severe hypoglycemia.AnimalsNinety horses (hours to 28 years of age) diagnosed with hypoglycemia (blood glucose concentration < 75 mg/dL [< 4.2 mmol/L]).MethodsRetrospective 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.ResultsThirty-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 importanceNeuroglycopenia 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).

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

BackgroundBrimonidine 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.ObjectivesTo 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 designA 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).MethodsPupil 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).ResultsThere 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 limitationsHorses with normal eyes may not be as sensitive to the IOP-lowering effects of treatment as horses with glaucoma.ConclusionsBrimonidine and brimonidine-timolol are well tolerated in normal horses but do not decrease IOP.

It has been previously been shown by our lab and others that persistent organic pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), are contaminants in milk produced for human consumption. To further this research we determined the concentration of 21 PCB and 14 PBDE congeners in livestock serum, mainly bovine, across California. Congeners were extracted from serum using solid phase extraction (SPE), cleaned up by silica cartridge and quantified using gas chromatography-triple quadruple mass spectrometry. We detected significant differences among species and the production class of cattle (beef or dairy). The sum of all 21 PCB congeners (ΣPCBs) in caprine and ovine sera had a mean value of 9.26 and 9.13 ng/mL, respectively, compared to 3.98 ng/mL in bovine sera. The mean value for the sum of all 14 PBDE congeners (ΣPBDEs) in caprine and ovine sera was 2.82 and 2.39 ng/mL, respectively, compared to 0.91 ng/mL in bovine sera. Mean ΣPCBs in dairy cattle was 5.92 ng/mL compared to 2.70 ng/mL in beef cattle. Mean ΣPBDEs in dairy cattle was 1.33 ng/mL compared to 0.70 ng/mL in beef cattle. There were no regional differences in the ΣPCBs or ΣPBDEs in cattle distributed across California. These results highlight the fact that livestock are still being exposed to these pollutants yet little is known about where this exposure may be coming from.

Experimental toxicological studies in laboratory animals and epidemiological human studies have reported a possible association between water fluoridation and osteosarcoma (OSA). To further explore this possibility, a case-control study of individual dogs evaluated by the UC Davis Veterinary Medical Teaching Hospital was conducted using ecologic data on water fluoridation based on the owner's residence. The case group included 161 dogs with OSA diagnosed between 2008-2012. Two cancer control groups included dogs diagnosed with lymphoma (LSA) or hemangiosarcoma (HSA) during the same period (n = 134 and n = 145, respectively). Dogs with OSA were not significantly more likely to live in an area with optimized fluoride in the water than dogs with LSA or HSA. Additional analyses within OSA patients also revealed no significant differences in age, or skeletal distribution of OSA cases relative to fluoride status. Taken together, these analyses do not support the hypothesis that optimal fluoridation of drinking water contributes to naturally occurring OSA in dogs.

BackgroundStandard 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.ObjectiveTo compare stimulation test results after IV and PV injections of ACTH.AnimalsTwenty privately owned dogs were studied: 10 healthy and 10 with trilostane-treated naturally occurring hyperadrenocorticism (HAC).MethodsProspective study. Each of 20 dogs underwent 2 ACTHst not

Canine chronic ulcerative stomatitis, also known as chronic ulcerative paradental stomatitis, is a painful condition of the oral cavity. The purpose of this study was to determine if there are commonalities in clinical and radiographic features among patients, whether the histopathologic evaluation might inform the pathogenesis, and whether the condition appears similar to human oral mucosal diseases. To do this, we prospectively collected clinical, radiographic, and histopathologic data from 20 dogs diagnosed with the disease. Clinical data were based on a clinical disease activity index, oral and periodontal examination parameters, and full-mouth dental radiographs. The histopathological and immunohistochemical data were based on oral mucosal samples obtained from erosive or ulcerated areas. Our findings revealed that canine chronic stomatitis is clinically characterized by painful oral mucosal ulcers of varying size, pattern, appearance, and distribution, most often associated with teeth with early periodontitis. Histologic examination revealed a subepithelial lichenoid band (interface mucositis) where B cells, T cells, and Forkhead-box protein 3 (FoxP3)- and interleukin-17-expressing cells were present. These cells might play a role in the underlying immune response and an immune-mediated pathogenesis is suspected. The clinical and histopathologic features of this chronic inflammatory mucosal disease in dogs resemble those of oral lichen planus in humans.

BackgroundDevelopment of hypocalcemia after treatment of hyperparathyroidism results in increased costs and risk of poorer outcomes. Previous studies have shown conflicting data about predictors of hypocalcemia after these procedures.Hypothesis/objectivesThe objective of this study was to investigate whether ionized calcium (iCa) concentrations before treatment are predictive of hypocalcemia or its clinical signs after surgical removal or heat ablation in dogs with primary hyperparathyroidism.AnimalsFifty-four dogs with primary hyperparathyroidism (29 female, 25 male; 49 retrospective, 5 prospective).MethodsDogs were enrolled if they met the inclusion criteria: persistent hypercalcemia (iCa >1.41 mmol/L) due to primary hyperparathyroidism and absence of preemptive calcitriol treatment. All dogs were treated with parathyroidectomy (n = 37) or percutaneous ultrasound-guided heat ablation (n = 17). After treatment, iCa was monitored twice daily until plateau or intervention.ResultsThere was a moderate correlation between before-treatment hypercalcemia and after-treatment hypocalcemia. The prospective study was terminated due to ethical concerns given findings in the retrospective section. All dogs were placed into groups according to their pretreatment iCa: 1.46-1.61 mmol/L, 1.62-1.71 mmol/L, iCa 1.72-1.81 mmol/L, or >1.81 mmol/L. After treatment, the mean lowest iCa for each group, respectively, was 1.19, 1.18, 1.13, and 1.01 mmol/L. There was a significant association between higher group and proportion of dogs with iCa

BackgroundImmune-mediated myositis (IMM) is a cause of rhabdomyolysis, stiffness, and muscle atrophy predominantly affecting Quarter horses. Limited information is available with regard to outcome, prognostic indicators, and associations with concurrent diseases.Hypothesis/objectivesTo report outcomes and associations between outcome and clinical and laboratory parameters, and presence of concurrent illness.AnimalsSixty-eight horses; 52 Quarter horses and related breeds and 16 other breeds.MethodsRetrospective cohort study (1991-2014). Medical records of horses with histological diagnosis of IMM were reviewed. Data recovery included signalment, laboratory variables, therapy, and outcome. Logistic regression was used to quantify the association between potential prognostic factors and survival to discharge.ResultsQuarter horses were younger (mean < 4 years, range 3 months-21 years) than other breeds (mean < 10 years, range 1-23 years). Pathogens causing concurrent or recent infection included S. equi equi, S. equi zooepidemicus, C. pseudotuberculosis, Anaplasma phagocytophilum, herpes virus-1, and influenza. The most common clinical signs consisted of rapidly progressive diffuse symmetrical muscle atrophy (80%), stiff gait (74%), and fever (44%). All horses that received medical therapy immediately upon admission survived to discharge (survival proportion = 87%). Leucocytosis was a common finding (60%). Horses with concurrent fever and other illness had a poor prognosis for hospital discharge.Conclusions and clinical importanceHorses with IMM can have a favorable outcome. Horses with concurrent fever and another illness had decreased probability of survival to discharge.

Museum specimens (maxillae and mandibles) of the three marmot species occurring in Alaska (Marmota caligata [n = 108 specimens], Marmota monax [n = 30] and Marmota broweri [n = 24]) were examined macroscopically according to predefined criteria. There were 71 specimens (43.8%) from female animals, 69 (42.6%) from male animals and 22 (13.6%) from animals of unknown sex. The ages of animals ranged from neonatal to adult, with 121 young adults (74.4%) and 41 adults (25.3%) included, and 168 excluded from study due to neonatal/juvenile age or incompleteness of specimens (missing part of the dentition). None of the teeth were missing, so 3,564 teeth were available for examination. All teeth were normal in morphology and none was affected by enamel hypoplasia. Two specimens displayed two supernumerary teeth each. One-third of specimens displayed attrition/abrasion and in 38.9% of these the change involved all premolar and molar teeth. The proportion of adult specimens affected by attrition/abrasion was three times as high as young adult specimens. Dental fractures were rare, noted in only two specimens, affecting 0.08% of teeth (n = 3). Periapical disease was also rare, with a striking lesion in one young adult female specimen. Some degree of periodontitis was seen in 26 specimens (16.1%), affecting 4.6% of premolar and molar teeth. The proportion of adults with periodontitis was over three times as high as that for young adults. Five specimens displayed mild malocclusion. Although the clinical significance of dental pathology in the marmot species of Alaska remains elusive, the occurrence and severity of some dental lesions may play an important role in their morbidity and mortality.

BackgroundThe prevalence and risk factors for infection with enteropathogens in dogs frequenting dog parks have been poorly documented, and infected dogs can pose a potential zoonotic risk for owners.Hypothesis/objectivesTo determine the prevalence and risk factors of infection with enteropathogens and zoonotic Giardia strains in dogs attending dog parks in Northern California and to compare results of fecal flotation procedures performed at a commercial and university parasitology laboratory.AnimalsThree-hundred dogs attending 3 regional dog parks in Northern California.MethodsProspective study. Fresh fecal specimens were collected from all dogs, scored for consistency, and owners completed a questionnaire. Specimens were analyzed by fecal centrifugation flotation, DFA, and PCR for detection of 11 enteropathogens. Giardia genotyping was performed for assemblage determination.ResultsEnteropathogens were detected in 114/300 dogs (38%), of which 62 (54%) did not have diarrhea. Frequency of dog park attendance correlated significantly with fecal consistency (P = .0039), but did not correlate with enteropathogen detection. Twenty-seven dogs (9%) were infected with Giardia, and genotyping revealed nonzoonotic assemblages C and D. The frequency of Giardia detection on fecal flotation was significantly lower at the commercial laboratory versus the university laboratory (P = .013), and PCR for Giardia was negative in 11/27 dogs (41%) that were positive on fecal flotation or DFA.Conclusions and clinical importanceEnteropathogens were commonly detected in dogs frequenting dog parks, and infection with Giardia correlated with fecal consistency. PCR detection of Giardia had limited diagnostic utility, and detection of Giardia cysts by microscopic technique can vary among laboratories.

Maxillae and/or mandibles from 76 walruses (Odobenus rosmarus) were examined macroscopically according to predefined criteria. The museum specimens were acquired between 1932 and 2014. Forty-five specimens (59.2%) were from male animals, 29 (38.2%) from female animals and two (2.6%) from animals of unknown sex, with 58 adults (76.3%) and 18 young adults (23.7%) included in this study. The number of teeth available for examination was 830 (33.6%); 18.5% of teeth were absent artefactually, 3.3% were deemed to be absent due to acquired tooth loss and 44.5% were absent congenitally. The theoretical complete dental formula was confirmed to be I 3/3, C 1/1, P 4/3, M 2/2, while the most probable dental formula is I 1/0, C 1/1, P 3/3, M 0/0; none of the specimens in this study possessed a full complement of theoretically possible teeth. The majority of teeth were normal in morphology; only five teeth (0.6% of available teeth) were malformed. Only one tooth had an aberrant number of roots and only one supernumerary tooth was encountered. No persistent deciduous teeth were found in any of the young adult or adult specimens, nor were any specimens affected by enamel hypoplasia. The majority of teeth (85.5%) displayed attrition/abrasion. Of the adult and young adult specimens, 90.8% showed some degree of attrition/abrasion on at least one tooth. Tooth fractures were noted in eight walruses, affecting 10.5% of specimens and 1.3% of the total number of teeth, nearly three-quarters of which were maxillary canine teeth (tusks). Three specimens (3.9%), all adult males, displayed overt periapical disease. The majority (99.2%) of dental alveoli did not have bony changes indicative of periodontitis, with only five specimens (6.6%) affected by periodontitis. Lesions consistent with temporomandibular joint osteoarthritis (TMJ-OA) were found in 46 specimens (60.5%) and TMJ-OA was significantly more common in adults than young adults and males than females. Although the clinical significance of dental and TMJ pathology in the walrus remains unknown, the occurrence and severity of these lesions may play an important role in the morbidity and mortality of this species.

BackgroundA scoring system for outcome prediction in dogs with acute kidney injury (AKI) recently has been developed but has not been validated.HypothesisThe scoring system previously developed for outcome prediction will accurately predict outcome in a validation cohort of dogs with AKI managed with hemodialysis.AnimalsOne hundred fifteen client-owned dogs with AKI.MethodsMedical records of dogs with AKI treated by hemodialysis between 2011 and 2015 were reviewed. Dogs were included only if all variables required to calculate the final predictive score were available, and the 30-day outcome was known. A predictive score for 3 models was calculated for each dog. Logistic regression was used to evaluate the association of the final predictive score with each model's outcome. Receiver operating curve (ROC) analyses were performed to determine sensitivity and specificity for each model based on previously established cut-off values.ResultsHigher scores for each model were associated with decreased survival probability (P < .001). Based on previously established cut-off values, 3 models (models A, B, C) were associated with sensitivities/specificities of 73/75%, 71/80%, and 75/86%, respectively, and correctly classified 74-80% of the dogs.Conclusions and clinical relevanceAll models were simple to apply and allowed outcome prediction that closely corresponded with actual outcome in an independent cohort. As expected, accuracies were slightly lower compared with those from the previously reported cohort used initially to develop the models.

The authors explored a possible relationship between coat color and aggressive behaviors in the domestic cat. This study used an Internet-based survey to collect information on coat color, affiliative behaviors toward cats/humans, agonistic behaviors toward cats/humans, other “problem” behaviors, and cat and guardian demographic data. A total of 1,432 cat guardians completed the online survey; after exclusions based on study protocol, data analysis included 1,274 completed surveys. Guardians reported sex-linked orange female (tortoiseshells, calicos, and “torbies”), black-and-white, and gray-and-white cats to be more frequently aggressive toward humans in 3 settings: during everyday interactions, during handling, and during veterinary visits. Kruskal-Wallis 1-way analysis of variance was used to compare possible differences between the 2 sexes and among different coat colors. Analyses of aggression due to handling, as well as aggression displayed during veterinarian visits, showed little difference among coat colors in these settings.

BackgroundBronchiectasis is a permanent and debilitating sequel to chronic or severe airway injury, however, diseases associated with this condition are poorly defined.ObjectiveTo evaluate results of diagnostic tests used to document bronchiectasis and to characterize underlying or concurrent disease processes.AnimalsEighty-six dogs that had bronchoscopy performed and a diagnosis of bronchiectasis.MethodsRetrospective case series. Radiographs, computed tomography, and bronchoscopic findings were evaluated for features of bronchiectasis. Clinical diagnoses of pneumonia (aspiration, interstitial, foreign body, other), eosinophilic bronchopneumopathy (EBP), and inflammatory airway disease (IAD) were made based on results of history, physical examination, and diagnostic testing, including bronchoalveolar lavage fluid analysis and microbiology.ResultsBronchiectasis was diagnosed in 14% of dogs (86/621) that had bronchoscopy performed. Dogs ranged in age from 0.5 to 14 years with duration of signs from 3 days to 10 years. Bronchiectasis was documented during bronchoscopy in 79/86 dogs (92%), thoracic radiology in 50/83 dogs (60%), and CT in 34/34 dogs (100%). Concurrent airway collapse was detected during bronchoscopy in 50/86 dogs (58%), and focal or multifocal mucus plugging of segmental or subsegmental bronchi was found in 41/86 dogs (48%). Final diagnoses included pneumonia (45/86 dogs, 52%), EBP (10/86 dogs, 12%) and IAD (31/86 dogs, 36%). Bacteria were isolated in 24/86 cases (28%), with Streptococcus spp, Pasteurella spp, enteric organisms, and Stenotrophomonas isolated most frequently.Conclusions and clinical importanceBronchiectasis can be anticipated in dogs with infectious or inflammatory respiratory disease. Advanced imaging and bronchoscopy are useful in making the diagnosis and identifying concurrent respiratory disease.

BackgroundDiagnosis of pancreatitis in dogs is complicated by extrapancreatic disorders that can alter the results of laboratory tests. Extrapancreatic disorders can also affect the diagnosis of exocrine pancreatic insufficiency (EPI). The effects of acute kidney injury (AKI) on pancreas-specific lipase activity (Spec cPL(®) Test), serum lipase activity and trypsin-like immunoreactivity (TLI) in dogs have not been evaluated.Hypothesis/objectivesSerum Spec cPL, lipase activity, and TLI concentrations will increase secondary to decreased kidney function.AnimalsFive purpose-bred dogs.MethodsExperimental prospective study. Gentamicin was used to induce AKI in 5 purpose-bred dogs. Serum samples were collected for measurement of creatinine, Spec cPL, lipase activity and TLI over 60 days, during both induction of, and recovery from, AKI.ResultsAll dogs developed and recovered from AKI. Six of 52 (12%) serum Spec cPL concentrations were increased (2 in the equivocal zone and 4 consistent with pancreatitis) in 2 of 5 (40%) dogs. Two of 51 (4%) serum lipase activity values were increased in 2 of 5 dogs. Serum TLI was increased above the reference range in 17 of 50 (34%) samples in 3 of 5 dogs. For all biomarkers, there was no consistent correlation with increases in serum creatinine concentration.Conclusions and clinical importanceDecreased renal excretion during experimental AKI did not cause consistent and correlated increases in serum Spec cPL, lipase activity, or TLI in this cohort of dogs.

BackgroundThe effects of anesthesia on the equine electroencephalogram (EEG) after administration of various drugs for sedation, induction, and maintenance are known, but not that the effect of inhaled anesthetics alone for EEG recording.ObjectiveTo determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses.AnimalsSix healthy horses.MethodsProspective study. Digital EEG with video and quantitative EEG (qEEG) were recorded after the administration of one of the 2 anesthetics, isoflurane or halothane, at 3 alveolar doses (1.2, 1.4 and 1.6 MAC). Segments of EEG during controlled ventilation (CV), spontaneous ventilation (SV), and with peroneal nerve stimulation (ST) at each MAC multiple for each anesthetic were selected, analyzed, and compared. Multiple non-EEG measurements were also recorded.ResultsSpecific raw EEG findings were indicative of changes in the depth of anesthesia. However, there was considerable variability in EEG between horses at identical MAC multiples/conditions and within individual horses over segments of a given epoch. Statistical significance for qEEG variables differed between anesthetics with bispectral index (BIS) CV MAC and 95% spectral edge frequency (SEF95) SV MAC differences in isoflurane only and median frequency (MED) differences in SV MAC with halothane only.Conclusions and clinical importanceUnprocessed EEG features (background and transients) appear to be beneficial for monitoring the depth of a particular anesthetic, but offer little advantage over the use of changes in mean arterial pressure for this purpose.

BackgroundKlebsiella spp. are implicated as a common cause of bacterial pneumonia in horses, but few reports describe clinical presentation and disease progression.Hypothesis/objectivesTo describe the signalment, clinicopathologic data, radiographic and ultrasonographic findings, antimicrobial susceptibility, outcome, and pathologic lesions associated with Klebsiella spp. pneumonia in horses.AnimalsForty-six horses from which Klebsiella spp. was isolated from the lower respiratory tract.MethodsRetrospective study. Medical records from 1993 to 2013 at the William R. Pritchard Veterinary Medical Teaching Hospital, University of California, Davis were reviewed. Exact logistic regression was performed to determine if any variables were associated with survival to hospital discharge.ResultsSurvival in horses

BackgroundPrevious study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings.ObjectivesTo determine the effects of 2 inhalation anesthetics on the EEG of healthy horses.AnimalsSix healthy horses.MethodsProspective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded during controlled ventilation, spontaneous ventilation, and nerve stimulation.ResultsBurst suppression was observed with isoflurane, along with EEG events that resembled epileptiform discharges. Halothane results were variable between horses, with epileptiform-like discharges and bursts of theta, alpha, and beta recorded intermittently. One horse died and 2 were euthanized as the result of anesthesia-related complications.Conclusions and clinical importanceThe results of this study indicate that the effects of halothane and isoflurane on EEG activity in the normal horse can be quite variable, even when used in the absence of other drugs. It is recommended that equine EEG be performed without the use of these inhalation anesthetics and that general anesthesia be induced and maintained by other contemporary means.

High-protein (HP) diets help prevent loss of lean mass in calorie-restricted (CR) cats. However, it is not entirely known whether these diets also induce changes of energy expenditure during periods of CR. To investigate this issue, sixteen overweight cats were fed either a high-protein [(HP), 54.2% of metabolizable energy (ME)] or a moderate-protein [(MP), 31.5% of ME] diet at 70% of their maintenance energy intakes for 8 weeks, and energy expenditure, energy intake, body weight and composition, and serum metabolites and hormones were measured. While both groups of cats lost weight at a similar rate, only cats eating the HP diet maintained lean mass during weight loss. Indirect respiration calorimetry measurements revealed that both total and resting energy expenditure (kcal/d) significantly decreased during weight loss for both treatment groups. However, only cats eating the MP diet exhibited significant decreases of total and resting energy expenditures after energy expenditure was normalized for body weight or lean mass. Results from this study suggest that in addition to sparing the loss of lean mass, feeding HP diets to overweight cats in restricted amounts may be beneficial for preventing or minimizing decreases of mass-adjusted energy expenditure during weight loss.

High-protein (HP) diets help prevent loss of lean mass in calorie-restricted (CR) cats. However, it is not entirely known whether these diets also induce changes of energy expenditure during periods of CR. To investigate this issue, sixteen overweight cats were fed either a high-protein [(HP), 54.2% of metabolizable energy (ME)] or a moderate-protein [(MP), 31.5% of ME] diet at 70% of their maintenance energy intakes for 8 weeks, and energy expenditure, energy intake, body weight and composition, and serum metabolites and hormones were measured. While both groups of cats lost weight at a similar rate, only cats eating the HP diet maintained lean mass during weight loss. Indirect respiration calorimetry measurements revealed that both total and resting energy expenditure (kcal/d) significantly decreased during weight loss for both treatment groups. However, only cats eating the MP diet exhibited significant decreases of total and resting energy expenditures after energy expenditure was normalized for body weight or lean mass. Results from this study suggest that in addition to sparing the loss of lean mass, feeding HP diets to overweight cats in restricted amounts may be beneficial for preventing or minimizing decreases of mass-adjusted energy expenditure during weight loss.

BackgroundSurvival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered.ObjectiveTo describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC).AnimalsClient-owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11).MethodsRetrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically.ResultsIntraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024).Conclusion and clinical importanceThis study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow-up time was short and the impact on long-term outcome and survival was not determined.

BackgroundRecent surveillance studies for equine respiratory viruses have shown that equine influenza virus (EIV) continues to be a prevalent respiratory virus of equids throughout the United States and Europe.ObjectivesTo gain a better understanding of the prevalence and epidemiology of EIV shed by horses, mules and donkeys in the United States from March 2010 to November 2013.Animals2,605 equids.MethodsNasal secretions from index cases with acute onset of respiratory disease were tested by qPCR for EIV. Multilevel logistic regression was used to model the association between EIV status and prevalence factors. Furthermore, observations from EIV-positive study horses were compared to previous data from March 2008 to February 2010.ResultsA total of 230 (9.7%) index cases tested qPCR positive for EIV. A higher-than-expected proportion of EIV qPCR-positive horses occurred in the 1-5, 6-10, and 11-15 age groups when compared to the

BackgroundFew studies report the minimum inhibitory concentrations for antimicrobials against equine Corynebacterium pseudotuberculosis isolates.Hypothesis/objectivesTo evaluate trends in the in vitro activities of 20 antimicrobials against equine Corynebacterium pseudotuberculosis isolates from 1996 to 2012 and to determine if a relationship exists between the minimum inhibitory concentration (MIC) and location of the abscess.AnimalsCorynebacterium pseudotuberculosis isolates from 196 horses with naturally occurring disease.MethodsRetrospective and cross-sectional design. Medical records were reviewed to obtain clinical and MIC data. Minimum inhibitory concentrations were determined by the microdilution technique. The MIC results over 3 periods were compared (1996-2001, 2002-2006, 2007-2012).ResultsThe MIC90 values for clinically relevant antimicrobials were as follows: chloramphenicol ≤ 4 μg/mL, enrofloxacin ≤ 0.25 μg/mL, gentamicin ≤ 1 μg/mL, penicillin =0.25 μg/mL, rifampin ≤ 1 μg/mL, tetracycline ≤ 2 μg/mL, trimethoprim-sulfamethoxazole (TMS) ≤ 0.5 μg/mL, ceftiofur =2 μg/mL, and doxycycline ≤ 2 μg/mL. There were no significant changes in MIC results over the study period. There was no relationship between MIC patterns and abscess location.Conclusions and clinical importanceThe MIC50 and MIC90 values of antimicrobials evaluated in this study for equine isolates of C. pseudotuberculosis did not vary over time. Abscess location was not associated with different MIC patterns in cultured isolates. Several commonly used antimicrobials are active in vitro against C. pseudotuberculosis in vitro.

Osteoarthritis, a degenerative disease of the load-bearing joints, greatly reduces quality of life for millions of Americans and places a tremendous cost on the American healthcare system. Due to limitations of current treatments, tissue engineering of articular cartilage may provide a promising therapeutic option to treat cartilage defects. However, cartilage tissue engineering has yet to recapitulate the functional properties of native tissue. During normal joint loading, cartilage tissue experiences variations in osmolarity and subsequent changes in ionic concentrations. Motivated by these known variations in the cellular microenvironment, this study sought to improve the mechanical properties of neocartilage constructs via the application of hyperosmolarity and transient receptor potential vanilloid 4 (TRPV4) channel activator 4α-phorbol 12,13-didecanoate (4αPDD). It was shown that 4αPDD elicited significant increases in compressive properties. Importantly, when combined, 4αPDD positively interacted with hyperosmolarity to modulate its effects on tensile stiffness and collagen content. Thus, this study supports 4αPDD-activated channel TRPV4 as a purported mechanosensor and osmosensor that can facilitate the cell and tissue level responses to improve the mechanical properties of engineered cartilage. To our knowledge, this study is the first to systematically evaluate the roles of hyperosmolarity and 4αPDD on the functional (i.e., mechanical and biochemical) properties of self-assembled neotissue. Future work may combine 4αPDD-induced channel activation with other chemical and mechanical stimuli to create robust neocartilages suitable for treatment of articular cartilage defects.

BackgroundTrilostane medical treatment of naturally occurring hyperadrenocorticism (NOH) in dogs is common, as is use of the adrenocorticotropic hormone (ACTH) stimulation test (ACTHst) in monitoring response to treatment. There is uncertainty regarding when the ACTHst should be started relative to time of trilostane administration.ObjectiveTo compare ACTHst results in dogs being treated for NOH with trilostane when the test is begun 2 versus 4 hours after trilostane administration.AnimalsTwenty-one privately owned dogs with NOH, each treated with trilostane for at least 30 days.MethodsEach dog had 2 ACTHst completed, 1 started 2 hours and the other 4 hours after trilostane administration. The second test was started no sooner than 46 hours and no later than 74 hours after the first.ResultsFor all 21 dogs, the mean post-ACTH serum cortisol concentration from tests started 2 hours after trilostane administration (5.4 ± 3.7 μg/dL) was significantly lower (P = .03) as compared with results from the tests started 4 hours after administration (6.5 ± 4.5 μg/dL).ConclusionsResults of ACTHst started at different times yield significantly different results. Dogs with NOH, treated with trilostane, and monitored with ACTHst results should have all of their subsequent ACTHst tests begun at or about the same time after trilostane administration.

This retrospective cohort study was aimed at describing the effects of age at acquisition, age, and duration of ownership of dogs on the risk of (1) bites during play and (2) non-play bites to humans. Data were collected on 110 dogs that had bitten during play with a person, 161 dogs that had bitten outside of play and 951 non-biting dogs from veterinary clients in Kingston (KGN), Jamaica and San Francisco (SF), USA. Modified Poisson regression was employed to model the relationships of both types of bites to each variable separately. Effects of the variables on dog bite risk (1) during and (2) outside of play with the dog, differed from each other and by type of bite. Effects varied with the dog's age and age-related associations were strongest in dogs younger than 1 year old. Ages at acquisition of dogs at highest risk for bites during play were substantially lower than those at risk for non-play bites. Ages and durations of ownership of dogs at highest risk for bites during play were also lower than those of dogs at highest risk for non-play bites. The propensity of a dog to bite changes as it ages and relationships between dog bites occurring during and outside of play and the dog's age at acquisition, current age, and duration of ownership, differ from each other.

A total of 4,626 mammals were serologically tested for antibodies to Sin Nombre virus. All nonrodent species were antibody negative. Among wild rodents, antibody prevalence was 8.5% in murids, 1.4% in heteromyids, and < 0.1% in sciurids. Of 1,921 Peromyscus maniculatus (deer mice), 226 (11.8%) were antibody positive, including one collected in 1975. The highest antibody prevalence (71.4% of 35) was found among P. maniculatus on Santa Cruz Island, off the southern California coast. Prevalence of antibodies among deer mice trapped near sites of human cases (26.8% of 164) was significantly higher than that of mice from other sites (odds ratio = 4.5; 95% confidence interval = 1.7, 11.6). Antibody prevalence increased with rising elevation (> 1,200 meters) and correlated with a spatial cluster of hantavirus pulmonary syndrome cases in the Sierra Nevada.

Objectives: The aim of this study was to prospectively evaluate in a randomized, triple-masked, placebo-controlled trial, outcomes for kittens with ocular manifestations of infectious upper respiratory disease (IURD) treated with an ophthalmic and oral antibiotic only vs those also treated with famciclovir., Methods: Kittens were stratified into three age (1 to <4, 4 to <8 or 8-12 weeks) and two disease severity ('mild' [total disease score 1-11] or 'severe' [total disease score 12-23]) groups and randomized to receive approximately 5 mg/kg doxycycline either with placebo (group D) or with approximately 90 mg/kg famciclovir (group DF) PO q12h. Caregivers scored clinical signs once daily for 21 days. Ophthalmic examinations and scoring by veterinarians were completed on days 1 and 21. Ophthalmic and clinical resolution were defined as scores of zero for all ocular signs and all ocular and respiratory signs, respectively. Ophthalmic and clinical recovery were defined by absence of active inflammation., Results: For kittens with mild disease, those in group D were slower than those in group DF to achieve clinical recovery ( P  = 0.049) and clinical resolution ( P  = 0.030), but not ophthalmic recovery ( P  = 0.064) or ophthalmic resolution ( P  = 0.089). Kittens with mild disease and receiving famciclovir achieved predicted 75% clinical resolution 4-5 days earlier than kittens with mild disease and receiving doxycycline alone, and kittens with severe disease (regardless of treatment group). Significantly fewer kittens in group DF developed corneal disease than in group D ( P  = 0.016). All five kittens whose clinical signs worsened sufficiently to be removed from the study were in group D., Conclusions and Relevance: The addition of famciclovir to standard antibiotic treatment may reduce corneal disease, length of stay and time to adoption for shelters and rescue groups, thereby increasing capacity for care. Early administration of famciclovir in kittens exhibiting mild ocular manifestations of IURD may be preferable to delaying this treatment until the disease progresses to a severe stage., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed., Methods: Six horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat., Results: The maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration., Discussion: Results of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared HS was an editorial member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Knych, Steinmetz, Traynham, McKemie and Kass.)

Ethanol, a central nervous system depressant and banned substance in horseracing, has reportedly been administered to horses prior to competition to "calm a horse's nerves." In this study, the pharmacokinetics of two metabolites of ethanol were studied to better understand the behavior of this compound in the horse and provide a scientific basis for regulation of its administration. Six horses received a single intravenous (30 mL; 1200 mg) and oral (90 mL; 3600 mg) administration of ethanol (vodka, 40% ABV) in a balanced cross-over design. Blood and urine samples were collected at various times post administration for up to 24 h. Concentrations of ethyl glucuronide and ethyl sulfate were determined using liquid chromatography-tandem mass spectrometry and pharmacokinetic analysis performed. Behavioral, locomotor activity and effects on heart rate were assessed. The maximum concentration (mean ± SD) of ethyl glucuronide was 71.5 ± 42.7 and 105.0 ± 47.5 ng/mL at 0.88 h following IV and oral administration, respectively. The maximum concentrations for the ethyl sulfate metabolite following IV and oral administration were 1.61 ± 0.60 and 3.46 ± 1.68 ng/mL, respectively. Urine concentrations of both metabolites were non-detectable by 24 h post ethyl alcohol administration. No observable behavioral responses were noted following IV or oral administration. Significant decreases in heart rate were noted at various times starting at 10 min until 4 h post administration in the oral dose group. Both ethyl glucuronide and ethyl sulfate could be useful markers for detection of illicit administration of ethanol to horses., (© 2024 The Author(s). Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Objective: This study describes the pharmacokinetics and pharmacodynamics, including antinociceptive effects, of a transdermal buprenorphine solution in horses. It was hypothesized that transdermal application would lead to sustained blood concentrations and antinociceptive effects with fewer adverse effects compared with intravenous (IV) injection., Study Design: Prospective nonrandomized four-part parallel experimental study., Animals: A group of eight horses (three mares and five geldings) aged 6-12 years., Methods: Horses were administered incremental doses of 15, 30 and 45 μg kg -1 of buprenorphine transdermal solution and a single IV dose of 5 μg kg -1 of buprenorphine with a 2 week washout period between treatments. Concentrations of buprenorphine were determined in plasma using liquid chromatography-tandem mass spectrometry and modeled using a nonlinear mixed effects population pharmacokinetic model to determine pharmacokinetic parameters. Pharmacodynamic effects, including changes in locomotor activity, heart rate, body temperature, gastrointestinal borborygmi, thermal and mechanical nociceptive thresholds were recorded. Mixed effects analysis of variance and post hoc comparisons were performed using a Bonferroni multiple comparison adjustment to assess differences in pharmacodynamic parameters between baseline and each time point within each dose group and between dose groups at the same time point., Results: Transdermal application of buprenorphine resulted in low systemic concentrations relative to IV injection. Bioavailability after transdermal application was 11%. Thermal nociceptive thresholds were significantly (p < 0.05) increased (4.3-10.7% relative to baseline) for up to 72 hours in the IV dose group, but only sporadically in the transdermal dose groups (2.5-9.9% relative to baseline). Changes in locomotor activity, heart rate and borborygmi varied over time and with dose., Conclusions and Clinical Relevance: Limited thermal antinociceptive effects were observed at the transdermal doses studied likely owing to limited absorption relative to IV dosing. Future studies may be directed toward investigating antinociceptive effects of higher transdermal doses and different application sites., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the impact of surgery resident training on surgery duration in tibial plateau leveling osteotomy (TPLO) and evaluate whether surgery duration differs with each year of residency training., Study Design: Retrospective medical record review., Animals: A total of 256 client-owned dogs underwent TPLO., Methods: Records of dogs that underwent TPLO between August 2019 and August 2022 were reviewed. The effects of the surgeon (faculty/resident) and the procedure (arthrotomy/arthroscopy) on TPLO surgery duration were examined with an analysis of variance, and geometric least squares means (GLSM) were compared. A linear mixed effects model (LMM) was fitted to quantify fixed and random effects., Results: Four faculty surgeons performed 74 (29%) TPLOs, while 10 residents performed 182 (71%) TPLOs under the direct supervision of a faculty surgeon. All TPLOs were conducted with arthrotomy (109; 43%) or arthroscopy (147; 57%). Overall, residents (GLSM, 153 min) required 54% more surgery duration than faculty surgeons (GLSM, 99 min). Surgery duration among first-year residents (GLSM, 170 min) was 15% longer than second- (GLSM, 148 min) and third-year (GLSM, 147 min) residents, whereas the duration did not differ statistically between second- and third-year residents. Arthroscopy, meniscal tear treatment, surgery on the right stifle, and increasing patient weight were also associated with longer surgery duration., Conclusion: The duration of TPLO surgery significantly decreased after the first year of residency, but did not decrease afterward., Clinical Significance: The results will aid with resource allocation, curricula planning, and cost management associated with resident training., (© 2024 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Ketoprofen is an anti-inflammatory drug that is commonly administered to racehorses for the alleviation of musculoskeletal pain and inflammation. This study represents a comprehensive examination of the metabolism (in vivo and in vitro), pharmacokinetics and ex vivo pharmacodynamics, of ketoprofen in horses. The in vitro metabolism as well as specific enzymes responsible for metabolism was determined by incubating liver microsomes and recombinant CYP450 and UGT enzymes with ketoprofen. For the in vivo portion, 15 horses were administered a single intravenous dose of 2.2-mg/kg ketoprofen. Blood and urine samples were collected prior to and up to 120 h post-drug administration. Additional blood samples were collected at select time points and were stimulated with calcium ionophore or lipopolysaccharide, ex vivo, to induce eicosanoid production. Drug, metabolite, and eicosanoid concentrations were determined using LC-MS/MS. Incubation of ketoprofen with equine liver microsomes generated 3-hydroxy ketoprofen, an unidentified hydroxylated metabolite, and ketoprofen glucuronide. Recombinant equine CYP2C23 produced the greatest amount of hydroxylated ketoprofen and recombinant equine UGT1A2 generated ketoprofen glucuronide. Dihydro, 3-hydroxy, and glucuronide metabolites were identified in blood and urine samples. The Vd ss was 0.280, 0.385, and 0.319 L/kg for total ketoprofen, S (+) ketoprofen, and R (-) ketoprofen, respectively. The mean half-life was 6.01 h for total ketoprofen, 2.22 h for S (+) ketoprofen, and 1.72 h for R (-) ketoprofen. Stimulation of ketoprofen-treated blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB 2 , PGE 2 , PGF 2alpha , LTB 4 , and 15(s)-HETE production for up to 120 h post-drug administration., (© 2023 John Wiley & Sons Ltd.)

Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus acetaminophen (1.2 mg/kg codeine and 6-6.4 mg/kg acetaminophen) in a three-way balanced crossover design. Plasma samples were collected, concentrations of drug and metabolites determined via liquid chromatography-mass spectrometry, and pharmacokinetic analyses were performed. Pharmacodynamic outcomes, including effect on thermal thresholds, were assessed. Codeine C max and AUC were significantly different between the codeine and combination group. There was considerable inter-individual variation in the pharmacokinetic parameters for codeine, acetaminophen, and their metabolites in horses. All treatments were well tolerated with minimal significant adverse effects. An increase in the thermal threshold was noted at 1.5 and 2 h, from 15 min through 6 h and 0.5, 1, 1.5, and 3 h in the codeine, acetaminophen, and combination groups, respectively., (© 2023 John Wiley & Sons Ltd.)

Background: Clodronate is a potent antiresorptive agent labelled for use in horses over 4 years of age, for the treatment of navicular syndrome. Concerns regarding the extra-label use of clodronate in equine athletes, such as racehorses, have been raised as inhibition of osteoclast activity by clodronate has been postulated to interfere with normal bone healing, which is imperative to the repair of microfractures. The paucity of data describing the long-term pharmacokinetics of clodronate and effects on biomarkers of bone resorption necessitates further study., Objectives: (1) To determine clodronate concentrations in blood and urine over a 6-month period in horses undergoing treadmill exercise and (2) to assess the effects of clodronate on protein biomarkers of bone remodelling in this same group of horses., Study Design: Randomised controlled experimental study., Methods: Seven exercised Thoroughbred horses received a single im administration of 1.8 mg/kg clodronate and four horses received an equivalent volume of saline. Blood and urine samples were collected prior to, during and for 182 days post drug administration for drug concentration determination using liquid chromatography-tandem mass spectrometry, and determination of protein biomarker (CTX-1 and TRAcP5B) concentrations., Results: Clodronate was detectable in blood for 14-175 days and for up to 175 days in urine. For some horses, concentrations were nondetectable at one time point but detectable at a subsequent time point. The terminal serum half-life ranged from 1.80 to 283.9 days. CTX-1 concentrations were significantly higher, relative to baseline, in both treated and control groups while concentrations of TRAcP5B were significantly lower in the treated group., Main Limitations: Relatively small number of horses studied., Conclusions: Based on assessment of protein biomarkers, clodronate appears to influence osteoclasts at label doses. Furthermore, results of this study support racing regulations that preclude horses administered bisphosphonates for medical reasons, from racing for a prolonged period of time., (© 2022 EVJ Ltd.)

The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6-glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2 mg/kg morphine and oral doses of 0.2, 0.6, and 0.8 mg/kg of morphine in a four-way balanced crossover design, with a 2-week washout period between doses. Concentrations of morphine and metabolites were determined, and pharmacokinetic parameters determined. Physiologic and behavioral outcomes including the number of steps taken, changes in heart rate, and gastrointestinal borborygmi were assessed. Oral administration of morphine resulted in higher concentrations of morphine metabolites, including M6G (C max : 11.6-37.8 ng/mL (0.6 mg/kg); 15.8-42.6 ng/mL (0.8 mg/kg)), compared with i.v. Bioavailability was 36.5%, 27.6% and 28.0% for 0.2, 0.6 and 0.8 mg/kg, respectively. Behavioral and physiologic changes were noted in all groups but were less prominent with oral compared with i.v. administration. Results of the current study are encouraging for further study, specifically anti-nociceptive effects of morphine following oral administration., (© 2023 John Wiley & Sons Ltd.)

Background: Gastrointestinal disease has been associated with shedding of Salmonella with previous studies demonstrating that horses with colic have a higher risk of acquiring and shedding Salmonella organisms., Objectives: The purpose of this study was to determine the prevalence of and risk factors associated with Salmonella shedding in a colic population at a referral clinic., Study Design: Retrospective case-control study., Methods: For each colic case that was positive for Salmonella (n = 56), two colic cases (n = 112) that tested negative for Salmonella, were enrolled as controls. Associations between variables and Salmonella shedding were identified using logistic regression. Univariate and multivariable models were developed pertaining to (1) presenting clinicopathological data and (2) clinical variables that developed during hospitalisation., Results: Of the equids presenting with colic, 1585/1917 had a sample submitted for Salmonella testing. Of these, 56 were positive for Salmonella yielding a prevalence of 3.5%. Equids shedding Salmonella were more likely to present in July (odds ratio [OR] = 7.2; 95% confidence interval [CI] = 1.63-32.13; p = 0.009) and present with a history of fever (OR = 53.5; 95% CI = 2.57-1113.03; p = 0.01), increased lactate (OR = 1.6; 95% CI = 1.14-2.29; p = 0.007) and/or neutropenia (OR = 0.79; 95% CI = 0.65-0.97; p = 0.02). Hospitalised equids shedding Salmonella were more likely to be febrile (OR = 4.8; 95% CI = 1.47-15.8; p = 0.01) and 10 times more likely to develop reflux (OR = 10.1; 95% CI = 1.67-61.43; p = 0.01) compared to colic controls., Main Limitations: Retrospective nature of the study and bias inherent to the retrieval of data from medical records cannot be discounted. Classifying Salmonella status based on a single sample may have resulted in misclassification bias., Conclusions: The prevalence of Salmonella shedding in this colic population was low compared to earlier reports. Certain predictors such as the development of a fever or reflux in hospitalised colic cases were associated with Salmonella shedding and may help the clinician to promptly identify horses likely to shed; thus, helping institute effective use of barrier nursing precautions., (© 2022 EVJ Ltd.)

Museum skull specimens from 224 Arctic foxes (Vulpes lagopus) were examined macroscopically using an established protocol for examination of mammalian skull specimens. Foxes were collected from coastal and island regions of Alaska, USA, except for two individuals. Collection years ranged from 1931 to 2016 with most specimens collected during the 1950s and 1960s. The study population comprised more females (n = 134, 59.8%) than males (n = 83, 37.0%) and individuals of unknown sex (n = 7, 3.1%). There were 108 (48.2%) young adults, 115 (51.3%) adults, and one (0.4%) individual of unknown age. A total of 8,891 teeth (94.5%) were available for examination. The most common types of pathology observed were periodontitis (n = 222, 99.1%), dental fractures (n = 175, 78.1%) and attrition/abrasion (n = 198, 88.4%). Periapical lesions (n = 12, 5.3%), temporomandibular joint (TMJ) osteoarthritis (n = 3, 1.3%) and root number variation (n = 5, 2.2%) were less common. Enamel hypoplasia was noted in eight foxes (3.6%), all of which were discovered on St. Matthew Island, Alaska, in 1963. As in other canid species, periodontitis, attrition/abrasion and tooth fractures are common in the Arctic fox, while TMJ pathology is rare. Loss of tooth crown substance probably reflects the influence of diet, interspecific and conspecific aggression and oral trauma due to trapping and hunting methods. The high prevalence of periodontitis is probably also due to the combined effects of diet, genetics and host immune reaction to oral bacteria., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (© 2022 British Small Animal Veterinary Association.)