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Objective To compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs. Study design A randomized, prospective, crossover experimental study. Animals A total of eight adult Beagle dogs (four female, four male), weighing 8.9–15.3 kg and aged 5–7 years. Methods The dogs were anesthetized three times with 1.25× minimum alveolar concentration of sevoflurane (SEVO treatment) and 1.25× minimum infusion rate of propofol (PROP treatment) or alfaxalone (ALFX treatment) at intervals of ≥14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC), a single bolus dose of rocuronium (1 mg kg–1) was administered intravenously. The times from rocuronium administration to achieving TOF count 0 (onset time), from achieving TOF count 0 to the reappearance of TOF count 4 (clinical blockade period), from 25% to 75% of TOFRC (recovery index) and from achieving TOF count 0 to TOF ratio/TOFRC >0.9 (total neuromuscular blockade duration) were recorded. Results The onset time and recovery index did not differ among the treatments. The median clinical blockade period was longer in the SEVO treatment [27.3 (26.0–30.3) minutes] than in PROP [16.6 (15.4–18.0) minutes; p = 0.002] and ALFX [22.4 (18.6–23.1) minutes; p = 0.017] treatments; and longer in the ALFX treatment than in the PROP treatment (p = 0.020). The mean total neuromuscular blockade duration was longer in the SEVO treatment (43.7 ± 9.9 minutes) than in PROP (25.1 ± 2.7 minutes; p Conclusions and clinical relevance Compared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.

Hui-jun Wang,1 Chun-yan Zhou,1 Yan-ding Su,1 Kai-feng Gou,1 Xiao-nan Geng,1 Xiang-jun Qiu1,2 1Department of Pharmacy, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People’s Republic of China; 2Functional Experiment Teaching Center, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People’s Republic of ChinaCorrespondence: Xiang-jun QiuFunctional Experiment Teaching Center, School of Basic Medical Sciences, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang, 471023, People’s Republic of ChinaTel +8613698882699Fax +86379-64830346Email lyxiangjun@126.comBackground: A new UPLC-MS/MS technique for the determination of ripretinib in beagle dog plasma was developed, and the pharmacokinetic effects of voriconazole and itraconazole on ripretinib in beagle dogs were studied.Methods: After extraction with ethyl acetate under alkaline conditions, ripretinib was detected using avapritinib as the internal standard (IS). The mobile phases were 0.1% formic acid-acetonitrile. The scanning method was multi-reaction monitoring using ESI+ source, and the ion pairs for ripretinib and IS were m/z 509.93→ 416.85 and 499.1→ 482.09, respectively. This animal experiment adopted a three period self-control experimental design. In the first period, ripretinib was orally administered to six beagle dogs at a dose of 5 mg/kg. In the second period, the same six beagle dogs were orally given itraconazole at a dose of 7 mg/kg, after 30 min, ripretinib was orally given. In the third period, voriconazole at a dose of 7 mg/kg was given orally, and then ripretinib was orally given. At different time points, the blood samples were collected. The concentration of ripretinib was detected, and the pharmacokinetic parameters of ripretinib were calculated.Results: Ripretinib had a good linear relationship in the range of 1– 1000 ng/mL. The precision, accuracy, recovery, matrix effect and stability met the requirements of the guiding principles. After erdafitinib combined with itraconazole, the Cmax and AUC0→t of ripretinib increased by 38.35% and 36.36%, respectively, and the t1/2 was prolonged to 7.53 h. After ripretinib combined with voriconazole, the Cmax and AUC0→t of ripretinib increased by 37.44% and 25.52%, respectively, and the t1/2 was prolonged to 7.33 h.Conclusion: A new and reliable UPLC-MS/MS technique was fully optimized and developed to detect the concentration of ripretinib in beagle dog plasma. Itraconazole and voriconazole could inhibit the metabolism of ripretinib in beagle dogs and increase the plasma exposure of ripretinib.Keywords: itraconazole, voriconazole, ripretinib, UPLC-MS/MS, pharmacokinetics, beagle dog

BACKGROUND Canine stomatocytosis is a well-recognized rare erythrocyte disorder characterized by nonsyndromic forms with selective erythroid involvement, syndromic forms with extra-hematologic disease, and acquired forms. OBJECTIVES We describe serial clinicopathologic changes in two dogs with stomatocytosis of breeds that are different from those previously reported. METHODS Blood samples were obtained from a 12-year-old female neutered Australian Cattle Dog and a 12-year-old male neutered Beagle for hematologic and biochemical analyses, including a morphologic examination of peripheral blood films. Serial clinicopathologic data were reviewed, including CBCs performed by the referring veterinary surgeons. RESULTS Serial CBC data in both cases reported a variable decrease in RBC numbers commonly associated with a normal hematocrit, macrocytosis, hypochromasia, changes in red cell distribution width parameters including marked histogram abnormalities in volume distribution of the RBC population, and mildly increased or normal reticulocyte counts. Morphologic examination of peripheral blood films identified variable numbers of stomatocytes, knizocytes (Case 1, Day 1, Day 4), mild anisocytosis, mild macrocytosis, and mild polychromasia. CONCLUSIONS In both cases, the changes exhibited in the erythrogram raise suspicion for an RBC membrane disorder with cell volume dysregulation and stomatocytosis, although they did not appear to cause clinically relevant hemolysis.

Like humans, weight control in overweight dogs is associated with a longer life expectancy and a healthier life. Dietary supplements are one of the best strategies for controlling obesity and obesity-associated diseases. This study was conducted to assess the potential of black ginseng (BG) and silkworm (SW) as supplements for weight control in diet-induced overweight beagle dogs. To investigate the changes that occur in dogs administered the supplements, different obesity-related parameters, such as body condition score (BCS), blood fatty acid profile, transcriptome, and microbiome, were assessed in high energy diet (HD) and HD with BG + SW supplementation (HDT) groups of test animals. After 12 weeks of BG + SW supplementation, total cholesterol and triglyceride levels were reduced in the HDT group. In the transcriptome analysis, nine genes (NUGGC, EFR3B, RTP4, ACAN, HOXC4, IL17RB, SOX13, SLC18A2, and SOX4) that are known to be associated with obesity were found to be differentially expressed between the ND (normal diet) and HD groups as well as the HD and HDT groups. Significant changes in some taxa were observed between the HD and ND groups. These data suggest that the BG + SW supplement could be developed as dietary interventions against diet-induced obesity, and obesity-related differential genes could be important candidates in the mechanism of the anti-obesity effects of the BG + SW supplement.

Determine the protein content and volume of tears sampled by Schirmer strips wetness ranging from 20 to 35 mm.Ten healthy beagle dogs.Each dog underwent 20 tear collections per day (10 sessions in each eye, spaced by ≥1 h) for 4 separate days, providing 200 tear samples for each length of wetness evaluated: 20, 25, 30, and 35 mm. A Schirmer strip was placed in each eye until the selected mm-mark was reached, calculating the volume absorbed (VA) as the difference between the post- and pre-collection weight (assuming 1 mg~1 µL for tear fluid), and the volume recovered (VR) as the amount pipetted from the tube following centrifugation. Total protein content (TPC) was measured with infrared spectroscopy. Outcome measures were compared with the Kruskal-Wallis test.Median values for VA (µL), VR (µL) and TPC (mg/mL) were as follows: 20 mm (18, 10, 5.94), 25 mm (22, 12.5, 5.97), 30 mm (25.5, 16, 5.89), and 35 mm (31, 22.5, 7.13). Both VA and VR were significantly greater (p .001) for Schirmer strips wetness of 35»30»25»20 mm. TPC was significantly greater (p .001) for 35 20-30 mm, but not among other groups (p = 1.000).The study established normative data to consider when canine studies use Schirmer strips to collect tears for bioanalytical purposes (eg, proteomics, pharmacokinetics). Although 35 mm yielded higher VA and VR, the higher TPC could be explained by greater disruption of ocular surface homeostasis. Absorption to 20-30 mm is the suggested length of strip wetness for bioanalytical tear collection in dogs.

Increased intracranial pressure (ICP) can cause irreversible pathological changes in the canine brain and can be life-threatening, so prompt diagnosis and therapeutic responses are warranted. The purposes of this prospective experimental study were to evaluate phase-contrast MRI (PC-MRI) as a non-invasive method for quantifying cerebrospinal fluid (CSF) and basilar artery flow, and to assess effects of intravenous administration of hypertonic fluid. A PC-MRI scan was acquired for six healthy Beagle dogs at the level of the mesencephalic aqueduct. Either 1.0 g/kg mannitol or isotonic saline solution was administered intravenously for 15 min each at a matched dose volume of 5 mL/kg. Basilar artery and CSF flow rates were measured and their values compared between mannitol and isotonic saline solution groups before administration, and subsequently every 15 min for 2 h post-administration. The CSF dynamics were further assessed by measuring repeat flow from the caudal to rostral direction and the rostral to caudal direction as the number of waves. No significant difference was observed in basilar or and CSF flow velocity between the two groups (P > .05). However, administration of isotonic saline solution tended to increase basilar artery velocity slightly over time, while CSF velocity remained unchanged. In the mannitol group, CSF wave forms tended to be reduced at 60 and 75 min (P > .05). Findings from this preliminary study indicated that it is feasible to measure the dynamics of CSF and basilar artery flow by PC-MRI, but no flow differences could be detected for mannitol versus isotonic saline administration.

The objective of this study was to investigate the influence of daily feeding of an oral care chew on the composition of canine supragingival plaque microbiota. Twelve beagle dogs were recruited to the randomized cross-over study. The dogs were fed one of two dietary regimes, both consisting of a commercially available wet and dry diet mix, either with or without daily supplementation with an oral care chew. After each 28-day test phase, supragingival plaque samples were collected and processed via Illumina sequencing to determine the microbiota composition. A comparative analysis of bacterial species associated with health and periodontal disease, identified from prior clinical studies, revealed differences between the dietary regimes. Consumption of the daily oral care chew, resulted in a significant increase in proportion of 6 health associated taxa but only 3 disease associated taxa compared to no chew. In contrast, 8 disease and 1 health associated taxa showed increased proportions for no chew versus the oral care chew. Daily feeding of the oral care chew tested in this study has therefore been shown to increase the proportion of health associated bacteria, over bacteria associated with periodontal disease, in supragingival plaque compared to no chew. By influencing plaque microbiota towards a bias for health associated bacteria, feeding of the oral care chew provides a means to reduce the prevalence of bacterial species shown to be associated with periodontal disease in dogs.

Background Proton pump inhibitors (eg, omeprazole) commonly are administered concurrently with nonsteroidal anti‐inflammatory drugs (NSAIDs; eg, carprofen) as prophylaxis to decrease the risk of gastrointestinal (GI) injury. However, evidence to support this practice is weak, and it might exacerbate dysbiosis and inflammation. Hypothesis/Objectives To evaluate the effect of carprofen alone or combined with omeprazole in dogs. We hypothesized that coadministration of omeprazole and carprofen would significantly increase GI permeability and dysbiosis index (DI) compared to no treatment or carprofen alone. Animals Six healthy adult colony beagle dogs. Methods Gastrointestinal permeability and inflammation were assessed by serum lipopolysaccharide (LPS) concentration, plasma iohexol concentration, fecal DI, and fecal calprotectin concentration in a prospective, 3‐period design. In the first 7‐day period, dogs received no intervention (baseline). During the 2nd period, dogs received 4 mg/kg of carprofen q24h PO for 7 days. In the 3rd period, dogs received 4 mg/kg of carprofen q24h and 1 mg/kg of omeprazole q12h PO for 7 days. Gastrointestinal permeability testing was performed at the end of each period. Data were analyzed using repeated measures mixed model analysis of variance with Tukey‐Kramer post hoc tests (P

Background Administration of moxidectin topically and doxycycline PO has been utilized experimentally as an alternative treatment for heartworm disease. However, clinical effects of this protocol remain poorly characterized. Objective To evaluate the clinical and postmortem findings associated with administration of doxycycline and monthly 10% imidacloprid + 2.5% moxidectin (IMD + MOX, Advantage Multi/Advocate) to Dirofilaria immitis‐experimentally infected as compared to nontreated control dogs. Animals Sixteen purpose‐bred, female, Beagle dogs. Methods Prospective, blinded, experimental study. Animals with surgically transplanted adult heartworms were randomized into 2 study groups of equal size: a nontreated control group (n = 8) and an IMD + MOX and doxycycline‐treated group (n = 8). Randomization was performed using a complete block design according to circulating microfilarial concentrations, measured before treatment. Serum biochemical profiles, CBCs, thoracic radiographs and echocardiograms were performed prior to and 3 weeks after transplantation, and monthly for 10 months. Postmortem gross and histopathologic evaluations were performed. Results Compared to control animals, mean ± SD serum alanine aminotransferase (181 ± 203 U/L vs 33 ± 7 U/L; P

Objective To evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs. Study design Randomized crossover experimental study. Animals A total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg. Methods Anesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg–1 hour–1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 μg kg–1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 μg kg–1 hour–1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 μg kg–1 minute–1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED50) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 μg kg–1 hour–1, obtained using log-linear regression analysis. Results The sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED50 values were lower when combined with dexmedetomidine than those obtained during saline–remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 μg kg–1 hour–1. Conclusions and clinical relevance Combined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.

Fasudil hydrochloride as an intracellular calcium ion antagonist that dilates blood vessels has exhibited a very potent pharmacological effect in the treatment of angina pectoris. The purpose of this study was to determine the absorption, distribution, and excretion profiles of fasudil in rats and beagle dogs, respectively, to clarify its pharmacokinetic pattern. A sensitive and reliable LC-MS/MS method has been developed and established and successfully applied to pharmacokinetic study, including absorption, tissue distribution, and excretion. The results revealed that in the range of 2-6 mg/kg, the pharmacokinetic behavior for instance, AUC and Cmax , in rats was observed in a dose dependent manner. However, the plasma concentrations were indicative of a significant gender difference in the pharmacokinetics of fasudil in rats, in terms of absolute bioavailability and excretion. Interestingly, the resulting data obtained from beagle dogs showed that there was no gender difference in the absolute bioavailability of fasudil hydrochloride after single or repeated administrations. In conclusion, this study characterized the pharmacokinetic pattern fasudil both in rats and beagle dogs through absorption, tissue distribution and excretion study. The findings may be valuable and provide a rationale for further study and its safe use in clinical practice.

We identified the presence of Renaut bodies in an unusual location in Beagle dogs on a 3-month nonclinical toxicity study. These peculiar structures are commonly reported as a background finding in the sciatic nerve of dogs. In our study, however, they were also observed in autonomic nerves surrounding the adrenal gland, a location in which they have not been reported before. The incidence in both locations were 8 of 32 Beagle dogs in the sciatic nerve and 6 of 40 Beagle dogs around the adrenal gland in the dosing and/or recovery phases of the study.

Bronchial collapse due to bronchomalacia is an important cause of chronic coughing in dogs. Radiographic and CT evidence of bronchial collapse has previously been reported in healthy Beagle dogs under forced expiration. However, published studies in brachycephalic dog breeds that are prone to bronchial collapse are currently lacking. In the present prospective analytical experimental study, CT and radiography were used to measure the bronchial diameter and collapsibility of each pulmonary bronchus during end-expiratory, 5 mL/kg forced-expiratory, and 10 mL/kg forced-expiratory phases in 17 asymptomatic brachycephalic dogs and six healthy Beagle dogs. Bronchial collapsibility was significantly greater during forced expiration, than that at the end of expiration in both groups (P < .001). Bronchial collapsibility measurements of the left lung lobes and the right cranial, middle, and accessory lobes were significantly higher in asymptomatic brachycephalic dogs than those in healthy Beagle dogs, during all expiratory phases (P < .05). The higher bronchial collapsibility of brachycephalic dogs was also supported using CT multiplanar reconstruction images and radiography. In conclusion, radiographic and CT measures of bronchial collapsibility in asymptomatic brachycephalic dogs are higher than measures in healthy Beagle dogs. Therefore, measures of bronchial collapse in brachycephalic dogs should not be evaluated using the same baseline measures as those used for healthy Beagle dogs.

OBJECTIVE To determine whether tropicamide, fluorescein, and proparacaine applied topically before sample collection affect the quantity or species of bacteria isolated via aerobic culture. ANIMALS STUDIED 12 female adult research beagle cross-breed dogs. PROCEDURES A conjunctival swab was taken before and after the sequential application of proparacaine, tropicamide, and fluorescein to the same eye (P/T/F) with a five-minute gap between medications. Paired swabs were submitted for aerobic culture. Bacterial enumeration was performed using the spread plate method. Following a one-week washout period, the procedure was repeated using balanced salt solution (BSS). Following a second one-week washout period, the experiment was repeated using ofloxacin 0.3% solution. Colony counts were compared using one-way ANOVA and Tukey post hoc comparison. Bacterial species reduction was compared using a Friedman rank test and Dunn's method. RESULTS The bacterial colony count for P/T/F and BSS was significantly higher than the ofloxacin group (p = 0.0052, p = 0.0022). There was no significant difference for colony counts between P/T/F and BSS (p = 0.9295). The most frequently isolated bacteria included: Psychrobacter spp., Staphylococcus spp., Corynebacterium spp., and Streptococcus spp. The bacterial species reduction for P/T/F and BSS was significantly lower than for ofloxacin (p

Objective To evaluate the efficacy of subcutaneous iohexol injection into the metatarsal region for thoracic duct lymphangiography in dogs and to determine the minimum effective dose. Study design Experimental study and clinical report. Animals Five healthy beagle dogs and one dog with chylothorax. Methods For the experimental study, iohexol was injected subcutaneously into the metatarsal region of five dogs at three doses (0.5, 0.75, and 1 mL/kg), and the injection sites were massaged gently. Computed tomography (CT) was performed 1, 3, 5, 7, 10, 15, and 20 minutes after iohexol injection. Subjective quality was assessed, and Hounsfield unit values were measured at several regions of interest (T1, T4, T8, T13, and L3). In the dog with chylothorax, iohexol (1.0 mL/kg) was injected into the right metatarsal region prior to CT. Results The thoracic duct was visualized and enhanced by contrast in all dogs after injection of 0.75 and 1.0 mL/kg of iohexol, and in two dogs after injection of 0.5 mL/kg at 3, 5, and 7 minutes. The thoracic duct was gradually attenuated with increasing doses of iohexol. In the dog with chylothorax, the entire thoracic duct was well enhanced and dilated, and tortuous cranial mediastinal lymphatics were detected. Conclusion The thoracic duct was visualized when at least 0.75 mL/kg of iohexol was injected subcutaneously into the metatarsal region of dogs. Clinical significance Subcutaneous injection of iohexol into the metatarsal region offers a simple alternative to conventional thoracic duct lymphangiography.

Background Two-dimensional shear wave elastography (2D-SWE) can noninvasively evaluate hepatic elastic modulus as shear wave velocity (SWV). Additionally, it may predict the presence of clinical relevant hepatic fibrosis (>= F2) in dogs with hepatic disease. Objectives To investigate whether SWV measured by 2D-SWE can differentiate between dogs with (>= F2) and without (F0-1) clinically relevant hepatic fibrosis. Animals Twenty-eight client-owned dogs with hepatic disease and 8 normal healthy Beagle dogs were enrolled. Methods In this cross-sectional prospective study, SWVs were measured using 2D-SWE in all dogs. Hepatic fibrosis stages and necroinflammatory activity grades were histopathologically evaluated using a histological scoring scheme that was adapted from the Ishak schema used in human medicine. Results Median SWVs were significantly higher in dogs with clinically relevant hepatic fibrosis (2.04 m/s; range, 1.81-2.26 m/s) than in healthy dogs (1.51 m/s; range, 1.44-1.66 m/s; P = .007), and dogs without clinically relevant hepatic fibrosis (1.56 m/s; range, 1.37-1.67 m/s; P < .001). However, no significant difference was found in the SWVs between dogs without clinically relevant hepatic fibrosis and healthy dogs (P = .99). Furthermore, median SWVs were not significantly different among dogs with necroinflammatory activity, those without necroinflammatory activity, and healthy dogs (Kruskal-Wallis test, P = .12). Conclusions and Clinical Importance The 2D-SWE may be useful for predicting the presence of hepatic fibrosis in dogs with hepatic disease.

The objective of this study was to develop a nonlinear mixed-effects model of vitacoxib disposition kinetics in dogs after intravenous (I.V.), oral (P.O.), and subcutaneous (S.C.) dosing. Data were pooled from four consecutive pharmacokinetic studies in which vitacoxib was administered in various dosing regimens to 14 healthy beagle dogs. Plasma concentration versus time data were fitted simultaneously using the stochastic approximation expectation maximization (SAEM) algorithm for nonlinear mixed-effects as implemented in Monolix version 2018R2. Correlations between random effects and significance of covariates on population parameter estimates were evaluated using multiple samples from the posterior distribution of the random effects. A two-compartment mamillary model with first-order elimination and first-order absorption after P.O. and S.C. administration, best described the available pharmacokinetic data. Final parameter estimates indicate that vitacoxib has a low-to-moderate systemic clearance (0.35 L hr-1 kg-1 ) associated with a low global extraction ratio, but a large volume of distribution (6.43 L/kg). The absolute bioavailability after P.O. and S.C. administration was estimated at 10.5% (fasted) and 54.6%, respectively. Food intake was found to increase vitacoxib oral bioavailability by a fivefold, while bodyweight (BW) had a significant impact on systemic clearance, thereby confirming the need for BW adjustment with vitacoxib dosing in dogs.

To evaluate a porous ZK60 magnesium alloy Bio-Transfix nail system compounded with bone morphogenetic protein-2 (BMP-2) on tendon-bone healing in a beagle anterior cruciate ligament reconstruction ...

Background Famotidine is sometimes administered as a continuous rate infusion (CRI) to treat gastrointestinal ulceration in critically ill dogs. However, clinical studies have not evaluated the efficacy of a famotidine CRI in dogs. Hypothesis/Objectives To evaluate the efficacy of famotidine at raising intragastric pH when it is administered as a CRI in dogs. We hypothesized that CRI treatment with famotidine would meet clinical goals for raising intragastric pH ≥3 and 4. Animals Nine healthy Beagle dogs. Methods Randomized 2‐way crossover. All dogs received 1.0 mg/kg IV q12h famotidine or CRI famotidine at 1.0 mg/kg IV loading dose and 8.0 mg/kg/d for 3 consecutive days. Beginning on day 0 of treatment, intragastric pH monitoring was used to continuously record intragastric pH. Mean percentage times (MPTs) for which intragastric pH was ≥3 and ≥4 were compared between groups using analysis of variance. Results There was a statistically significant difference (P

Background To evaluate the pharmaceutical safety of Myelophil, an ethanol extract of a mixture of Astragali Radix and Salviae Miltiorrhizae Radix, using both acute and repeated toxicological studies. Methods A total of 40 beagle dogs (20 each male and female) were fed doses up to 5,000 mg/kg for the acute study and up to 1,250 mg/kg for the 13-week repeated dose toxicological study. Adverse effects were examined intensively by comparing the differences between normal and drug-administered groups using clinical signs, autopsies, histopathological findings, hematology, urinalysis, and biochemical analysis. Results No mortality or drug-related clinical signs were observed in the Myelophil-treated groups, except for vomiting due to an excessive dose (5,000 mg/kg). Likewise, in the repeated toxicity test, compound-colored stools in the Myelophil-treated groups and soft stools in all groups, including the control, were observed. No drug-related abnormalities were found in the histopathology, hematology, urinalysis, and biochemical analyses for any doses of Myelophil. Conclusion These results support the safety of Myelophil with a no observed adverse effect level (NOAEL) of 1250 mg/kg in beagle dogs, which corresponds to a human equivalent dose (HED) of 694 g/kg. Electronic supplementary material The online version of this article (10.1186/s12906-019-2588-3) contains supplementary material, which is available to authorized users.

Background Canine brucellosis , caused by the bacterium Brucella canis , is a zoonotic and largely reproductive disease of dogs. The disease is a recognized problem in canine breeding populations, and the risk to individuals assisting with birthing is well described. Prior to 2015, all cases of canine brucellosis reported to the Minnesota Board of Animal Health were in dogs used for breeding. In 2015, canine brucellosis was identified in eight Minnesota rescue dogs, all originating from specific geographic areas in South Dakota. Our objective was to measure the seroprevalence of B. canis in stray and previously owned dogs entering a large Minnesota animal rescue organization to determine if our observations represented a localized or generalized disease issue among rescue dogs. Methods A stratified random sample of stray and previously owned dogs entering the largest Minnesota animal rescue organization between November 1, 2016 and November 7, 2017, was tested for B. canis antibodies by the 2-Mercaptoethanol Rapid Slide Agglutination Test (2ME-RSAT) (Zoetis d -TEC® CB kit). Sample sizes for each strata were calculated using previously published seroprevalence estimates. Blood from selected dogs was collected, serum harvested, and transported to the Minnesota Veterinary Diagnostic Laboratory for testing. Positive samples in the 2ME-RSAT were shipped to Cornell University for confirmation by Agarose Gel Immunodiffusion (AGID) testing. Demographics, state and setting of origin, and health status were collected on study-dogs. Results Of the 10,654 dogs accepted by AHS during the study period, 943 (8.9%) were selected for testing. Most study dogs arrived from Oklahoma (28%), Alabama (18%), and Minnesota (12%). The median age of study dogs was 1.5 years; 303 (32%) were intact males and 294 (31%) were intact females. Most study dogs were strays (n = 716, 76%). Of the total, 22 (3.1%) stray and eight (3.5%) owner-surrendered dogs were presumptively positive by RSAT; one (0.11%) of the stray dogs was positive by 2ME-RSAT and confirmed by AGID. The positive dog was a healthy-appearing 1 year-old neutered male beagle from Texas. Conclusions The seroprevalence of canine brucellosis in dogs entering Minnesota for adoption from multiple states was low. Never-the-less, care must to be taken to consider all potential risks and outcomes of interstate and international dog trade, including the spread of infectious diseases such as canine brucellosis.

Background Steroid-responsive meningitis-arteritis (SRMA) is a common inflammatory neurologic disorder of dogs for which certain breeds are predisposed. Objectives To determine whether breed differences exist in clinical features, treatment response, and relapse in a population of North American dogs with SRMA, and to evaluate the effect of disease on dogs' quality of life (QoL). Animals Sixty-one client-owned dogs with SRMA: 29 dogs identified through an American Kennel Club-Canine Health Foundation survey and 32 dogs from North Carolina (NC) State Veterinary Hospital. Methods Retrospective case series. Caregivers completed an online survey to assess QoL. Results Breeds represented most often included the Golden Retriever (n = 12), Bernese Mountain Dog (10), Wirehaired Pointing Griffon (9), Boxer (9), and Beagle (6). No breed differences were identified with respect to clinical severity, diagnostic findings, or outcome. Twenty-nine dogs (48%) had ≥1 disease relapse. There was a significant effect of cerebrospinal fluid nucleated cell count on the frequency of disease relapse (P = .003), but no relationship was identified between treatment protocol and relapse. Dogs' QoL was associated with the severity of corticosteroid-related adverse effects (P = .03), which were dose-related (r = .24, P = .02) and more prevalent in Wirehaired Pointing Griffons than in other breeds (P = .04). Conclusion and clinical importance Golden Retrievers and Wirehaired Pointing Griffons should be considered among the breeds recognized to develop SRMA. Treatment with higher corticosteroid dosages is correlated with more severe adverse effects and worse QoL, but it may not improve clinical outcome.

In people, the antifibrinolytic drug tranexamic acid reduces bleeding and the need for blood products with both normal and exaggerated fibrinolysis without increasing the number of thromboembolic events. In dogs, in addition to prevention and treatment of bleeding, higher doses of tranexamic acid can be used to induce vomiting. The objective of this study was to evaluate the effect of a high dose of tranexamic acid on the coagulation of healthy Beagle dogs. A prospective trial was conducted in eight healthy Beagles receiving tranexamic acid for a concurrent trial evaluating different antiemetics. Rotational thromboelastometry (ROTEM) analysis (EXTEM, APTEM, FIBTEM, INTEM) was performed before and 30 minutes after intravenous administration of 50 mg/kg tranexamic acid. ROTEM parameters before and after tranexamic acid administration and between EXTEM and APTEM were compared with Wilcoxon matched-pairs signed rank test and data is presented as median (range). After tranexamic acid administration, FIBTEM clotting time became significantly shorter (p=0.03) from 37 s (28-124 s) to 33 s (27-40 s) and INTEM clot formation time significantly decreased (p=0.02) from 82 s (47-132 s) to 60 s (43-107 s). After tranexamic acid APTEM MCF was significantly weaker (p=0.01) with 45 mm (30-63 mm) than EXTEM MCF with 55 mm (43-69 mm) and than APTEM MCF before tranexamic acid with 55 mm (43-69 mm) (p=0.02). All other analysed parameters including maximum lysis did not change after administration of tranexamic acid. The administration of 50 mg/kg intravenous tranexamic acid resulted in small changes in ROTEM profiles without inducing a hypercoagulable clot. In conclusion, tranexamic acid can safely be administered to healthy dogs with normal coagulation profiles. As an additional finding, APTEM parameters measured in the current study do not support the use of this test in dogs.Der antifibrinolytische Wirkstoff Tranexamsäure reduziert beim Menschen Blutungen und den Bedarf an Blutprodukten, dies sowohl bei normaler als auch bei übertriebener Fibrinolyse und ohne die Anzahl der thromboembolischen Ereignisse zu erhöhen. Bei Hunden können höhere Dosen von Tranexamsäure neben der Vorbeugung und Behandlung von Blutungen auch zur Induktion von Erbrechen verwendet werden. Ziel dieser Studie war es, die Wirkung einer hohen Dosis Tranexamsäure auf die Koagulation von gesunden ­Beagle-Hunden zu bewerten. Die prospektive Studie wurde bei acht gesunden Beagles durchgeführt, die Tranexamsäure während einer Studie zur Bewertung verschiedener Antiemetika erhielten. Rotations-Thromboelastometrie (ROTEM) Analyse (EXTEM, APTEM, FIBTEM, INTEM) wurde vor und 30 Minuten nach intravenöser Verabreichung von 50 mg/kg Tranexamsäure durchgeführt. Die ROTEM-Parameter vor und nach der Verabreichung von Tranexamsäure und zwischen EXTEM und APTEM wurden mit dem Wilcoxon-Matched-Pair-Test verglichen und der Medianwert (Range) angegeben. Nach der Verabreichung von Tranexamsäure wurde die Gerinnungszeit von FIBTEM von 37 s (28-124 s) auf 33 s (27-40 s) signifikant verkürzt (p = 0,03) und die Bildung der INTEM-Gerinnsel reduzierte sich signifikant (p = 0,02) von 82 s ( 47-132 s) auf 60 s (43-107 s). Nach Tranexamsäure war APTEM MCF mit 45 mm (30-63 mm) signifikant schwächer (p = 0,01) als EXTEM MCF mit 55 mm (43-69 mm) und als APTEM MCF vor Tranexamsäure mit 55 mm (43-69 mm) (p = 0,02). Alle anderen analysierten Parameter einschließlich der maximalen Lyse änderten sich nach Verabreichung von Tranexamsäure nicht. Die Verabreichung von 50 mg/kg intravenöser Tranexamsäure führte zu kleinen Änderungen der ­ROTEM-Profile, ohne ein hyperkoagulierbares Gerinnsel zu induzieren. Zusammenfassend kann Tranexamsäure gesunden Hunden mit normalen Gerinnungsprofilen sicher verabreicht werden. Als zusätzliches Ergebnis der aktuellen Studie konnten die gemessenen APTEM-Parameter die Verwendung dieses Tests bei Hunden nicht bestätigen.Chez l’homme présentant une fibrinolyse normale et exagérée, l’acide tranexamique, un agent antifibrinolytique, réduit les saignements et le besoin de produits sanguins sans augmenter le nombre d’événements thromboemboliques. Chez les chiens, en plus de la prévention et du traitement des saignements, des doses plus élevées d’acide tranexamique peuvent être utilisées pour provoquer des vomissements. L’objectif de cette étude était d’évaluer l’effet d’une dose élevée d’acide tranexamique sur la coagulation de chiens Beagle en bonne santé. Un essai prospectif a été mené chez huit Beagles en bonne santé recevant de l’acide tranexamique dans le cadre d’un essai simultané évaluant différents antiémétiques. Une analyse de la thromboélastométrie rotationnelle (ROTEM) (EXTEM, APTEM, FIBTEM, INTEM) a été réalisée avant et 30 minutes après l’administration intraveineuse de 50 mg/kg d’acide tranexamique. Les paramètres ROTEM avant et après l’administration d’acide tranexamique et entre EXTEM et APTEM ont été comparés au test de rang de Wilcoxon à paires appariées et les données sont présentées sous forme de médiane. Après administration de l’acide tranexamique, le temps de coagulation de FIBTEM est devenu significativement plus court (p = 0,03) de 37 s (28-124 s) à 33 s (27-40 s) et le temps de formation du caillot INTEM a été significativement réduit (p = 0,02) de 82 s (47-132 s) à 60 s (43-107 s). Après l’acide tranexamique, APTEM MCF était significativement plus faible (p = 0,01) avec 45 mm (30-63 mm) que EXTEM MCF avec 55 mm (43-69 mm) et qu’APTEM MCF avant l’acide tranexamique avec 55 mm (43-69 mm) (p = 0,02). Tous les autres paramètres analysés, y compris la lyse maximale, n’ont pas changé après l’administration d’acide tranexamique. L’administration de 50 mg/kg d’acide tranexamique par voie intraveineuse a entraîné de légers changements dans les profils ROTEM sans induire de caillot hypercoagulable. En conclusion, l’acide tranexamique peut être administré en toute sécurité à des chiens en bonne santé présentant des profils de coagulation normaux. Autre constatation supplémentaire, les paramètres APTEM mesurés dans la présente étude n’appuient pas l’utilisation de ce test chez le chien.Nelle persone, il farmaco antifibrinolitico acido tranexamico riduce l’emorragia e la necessità di prodotti ematici con fibrinolisi normale ed esagerata senza aumentare il numero di eventi tromboembolici. Nei cani, oltre alla prevenzione e al trattamento dell’emorragia, dosi più elevate di acido tranexamico possono essere utilizzate per indurre il vomito. L’obiettivo di questo studio è stato quello di valutare l’effetto di un’alta dose di acido tranexamico sulla coagulazione dei cani Beagle sani. È stato condotto uno studio prospettico in otto Beagle sani a cui veniva somministrato acido tranexamico per uno studio concomitante che valutava diversi antiemetici. L’analisi tromboelastografica rotazionale (ROTEM) (EXTEM, APTEM, FIBTEM, INTEM) è stata eseguita prima e 30 minuti dopo la somministrazione endovenosa di 50 mg/kg di acido tranexamico. I parametri ROTEM prima e dopo la somministrazione di acido tranexamico e tra EXTEM e APTEM sono stati confrontati con il test di Wilcoxon dei ranghi con segno con misure accoppiate e i dati sono stati presentati come mediana (rango). Dopo la somministrazione di acido tranexamico, il tempo di coagulazione FIBTEM è diventato significativamente più breve (p=0.03) da 37 s (28-124 s) a 33 s (27-40 s) e il tempo di formazione del coagulo INTEM è diminuito significativamente (p=0.02) da 82 s (47-132 s) a 60 s (43-107 s). Dopo la somministrazione dell’acido tranexamico APTEM MCF era significativamente più debole (p=0.01) con 45 mm (30-63 mm) di EXTEM MCF con 55 mm (43-69 mm) e di APTEM MCF prima dell’acido tranexamico con 55 mm (43-69mm) (p=0.02). Tutti gli altri parametri analizzati, compresa la lisi massima, non sono cambiati dopo la somministrazione di acido tranexamico. La somministrazione di 50 mg/kg di acido tranexamico per via endovenosa ha portato a piccole modifiche nei profili ROTEM senza indurre un coagulo trombofilo. In conclusione, l’acido tranexamico può essere somministrato con sicurezza nei cani sani con profili di coagulazione normali. Come ulteriore risultato, i parametri APTEM misurati nello studio attuale non supportano l’uso di questo test nei cani. Parole chiave: Antifibrinolitico, canino, emetico, acido tranexamico, test di coagulazione viscoelastica, vomito.

Although various artificial tracheas have been developed, none have proven satisfactory for clinical use. In-body tissue architecture (IBTA) has enabled us to produce collagenous tissues with a wide range of shapes and sizes to meet the needs of individual recipients. In the present study, we investigated the long-term outcomes of patch tracheoplasty using an IBTA-induced collagenous tissue membrane (“biosheet”) in a beagle model. Nine adult female beagles were used. Biosheets were prepared by embedding cylindrical molds assembled with a silicone rod and a slitting pipe into dorsal subcutaneous pouches for 2 months. The sheets were then implanted by patch tracheoplasty. An endoscopic evaluation was performed after 1, 3, or 12 months. The implanted biosheets were harvested for a histological evaluation at the same time points. All animals survived the study. At 1 month after tracheoplasty, the anastomotic parts and internal surface of the biosheets were smooth with ciliated columnar epithelium, which regenerated into the internal surface of the biosheet. The chronological spread of chondrocytes into the biosheet was observed at 3 and 12 months. Biosheets showed excellent performance as a scaffold for trachea regeneration with complete luminal epithelium and partial chondrocytes in a 1-year beagle implantation model of patch tracheoplasty.

In preclinical research, Beagle dogs are an important model for formulation development and for evaluation of food effects on drug absorption. In this study, the gastrointestinal transit conditions in Beagle dogs were studied with a telemetric motility capsule at different intake conditions. In a cross-over study design, the SmartPill® was given to six Beagle dogs to measure transit times, pH values, pressures and temperatures in the different parts of the canine GI tract. Moreover, the effects of commonly applied pre-treatments as with pentagastrin and famotidine on GI transit conditions were investigated. The gastric transit time in fasted state was short (0.57 ± 0.37 h) and only slightly affected by the pre-treatments. In fed state, gastric transit was clearly prolonged (2.94 ± 0.91 h). The mean intestinal transit time was in the range of 1–2 h and not affected by the intake conditions. The gastric pH values in fasted and fed Beagle dogs were highly variable, but pre-treatment with pentagastrin and famotidine clearly decreased variability. Pre-treatment with pentagastrin resulted in minimum pH values around 0.5 pH units lower than without pre-treatment. Oral administration of famotidine led to constantly elevated pH values of pH 7–8. The maximum pressures in the canine GI tract did not vary significantly between the study arms and typically, maximum pressures of up to 800 mbar were observed in the stomach. The comparison of the data from this study with recent SmartPill® data from humans revealed that major differences could be observed with respect to gastric transit times in fed state, small intestinal transit times as well as maximum pressures arising during GI transit. These differences should be kept in mind if the dog model is used to assess the in vivo performance of solid oral dosage forms intended for use in humans.

Objective To assess the pharmacokinetics (PK) and conduct a clinical laboratory evaluation of acetaminophen in Beagle and Galgo Espanol (GE) dogs. Study design Prospective randomized experimental trial. Animals A total of 20 healthy dogs – 10 Beagles and 10 GE (six males and four females in both groups). Methods Acetaminophen (10 and 20 mg kg–1) was administered intravenously (IV) to the dogs on two different occasions. Plasma concentrations were analysed by high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling with ADAPT 5 software. Simulations after multiple IV doses were investigated. Clinical laboratory values such as red blood cell (RBC) count, haemoglobin (Hb), haematocrit (Ht), white blood cell (WBC) count, platelet count, total proteins, alanine aminotransferase (ALT), aspartate aminotransferase, urea and creatinine were measured before and 24 hours after acetaminophen administration in combination with clinical examination to assess side effects resulting from the drug. Results A two-compartmental model best described time–concentration profiles of acetaminophen. PK parameters were different as a result of a breed effect. For doses of 10 and 20 mg kg–1, respectively, clearance values were 1.70 (1.15–2.27) and 1.62 (1.06–2.86) L kg–1 hour–1 for Beagles and 1.18 (0.70–1.39) and 1.08 (0.67–1.35) L kg–1 hour–1 for GE; elimination half-life values were 2.64 (0.52–4.46) and 2.86 (0.87–4.63) hours for Beagles and 3.49 (1.89–7.80) and 4.57 (2.08–8.90) hours for GE. Significant differences were also found between GE and Beagles in the RBC count, Ht, Hb, WBC count and serum ALT before drug administration, and these differences were maintained 24 hours later, independent of the dosage used. For each breed, no side effects resulting from IV acetaminophen administration were observed at doses of either 10 or 20 mg kg–1. Conclusions and clinical relevance IV PK of acetaminophen was different between Beagles and GE dogs. Side effects were not detected. Further studies are necessary to evaluate the PK in a clinical context.

This study evaluated the effect of sevoflurane anesthesia on neuromuscular blockade with rocuronium in dogs. Six healthy beagle dogs were anesthetized four times with a minimum 14-day washout period. On each occasion, the dogs were administered 1.25-, 1.5-, 1.75-, or 2.0-fold of the individualized minimum alveolar concentration (MAC) of sevoflurane and received an infusion of rocuronium (0.5 mg/kg followed by 0.2 mg/kg/hr) for 120 min. Neuromuscular function was monitored with acceleromyography and train-of-four (TOF) stimulation of the left hind limb. Time to achieve TOF count 0 (onset time), time from the onset of neuromuscular blockade to the reappearance of TOF count 4 (blockade period), and time from the onset of rocuronium infusion to attaining a 70 or 90% TOF ratio (TOFR70 or TOFR90) were recorded. There were no significant differences in the onset time, blockade period, and plasma rocuronium concentration between the sevoflurane MAC multiples. The TOFR70 and TOFR90 were dose-dependently prolonged with the sevoflurane MAC multiples. There were significant differences in the TOFR70 and TOFR90 between the 1.25 sevoflurane MAC (median: 55 and 77.5 min, respectively) and 1.75 sevoflurane MAC (122.0 and 122.6 min; P=0.020 and P=0.020, respectively), 1.25 sevoflurane MAC and 2.0 sevoflurane MAC (126.0 and 131.4 min; P=0.020 and P=0.020), and 1.5 sevoflurane MAC (97.5 and 121.3 min) and 2.0 sevoflurane MAC (P=0.033 and P=0.032). In dogs, sevoflurane anesthesia produced dose-dependent prolongation of recovery from neuromuscular blockade produced by rocuronium.

Twelve adult beagle dogs (10.6 ± 1.4 kg) were fed extruded dog diets in which the starch sources were whole sorghum, sorghum flour, sorghum mill-feed, or an equal combination of rice, corn, and wheat. The experiment was conducted as a replicated Latin square design digestibility study. Estimates of fecal organic matter (OM), crude protein (CP), crude fat (CF), and gross energy (GE) outputs were determined by four methods: total fecal collection (TFC), chromic oxide (Cr2O3), titanium dioxide (TiO2), and acid insoluble ash (AIA). The correlation among the fecal output estimates by the four methods by partial correlation coefficients from the Error SSCP Matrix (Pearson) were considered significant at P < 0.05. The external markers, Cr2O3 and TiO2, had a higher (P < 0.05) OM fecal output Pearson correlation to TFC than the intrinsic marker AIA (R = 0.931 for Cr2O3 vs. TiO2; R = 0.559 for TFC vs. Cr2O3; R = 0.592 for TFC vs. TiO2; R = 0.291 for AIA vs. TFC). Interestingly, TiO2 highly correlated (P < 0.05) to Cr2O3 (R = 0.93 for OM), and was also correlated highly to TFC and AIA. The study suggests that TiO2 may be a preferred marker to estimate fecal output in dogs vs. Cr2O3. The use of AIA represents a potential option for determining digestibility for diets in which external markers are impractical.

We investigated the effects of tyrosol (Tyr) on anterior chamber paracentesis (ACP)-induced anterior uveitis in beagle dogs, as determined by protein and prostaglandin E2 (PGE2) concentrations in the aqueous humor (AH). Tyr at a dose of 100 or 200 mg/kg or 2.2 mg/kg of carprofen as a positive control was administered orally twice daily from 2.5 days before paracentesis. The initial ACP was performed in one eye of individual dogs and 0.5 ml AH was aspirated. The secondary AH was collected 60 min later. Pretreatment with 200 mg/kg of Tyr and carprofen significantly decreased aqueous protein and PGE2 concentrations compared to the control group. Overall, these findings suggested that Tyr was useful for the management of canine anterior uveitis.

Anterior cruciate ligament (ACL) reconstruction is the leading treatment for ACL rupture. Ligament Advanced Reinforcement System (LARS), which is made of polyethylene terephthalate (PET), is the most frequently used artificial ligament for ACL reconstruction. However, PET is hydrophobic, so it is difficult to induce the ingrowth of the autologous tissue. The aim of this study is to explore the effects of silk hybrid on the ligamentization of the PET artificial ligament in a canine ACL reconstruction model. Silk/PET hybrid suspensory ligament was fabricated with silk in the weft yarn and PET in the warp yarn, while PET suspensory ligament was fabricated with PET in both the weft and warp yarns. After fabrication, the micromorphology of the ligaments was observed and mechanical testing was performed. Though the failure loads of the degummed silk/PET hybrid suspensory ligaments were significantly lower than those of the PET suspensory ligaments (P < 0.001), both of them were enough for ACL reconstructions of beagle dogs. In the animal study, 14 beagle dogs were divided into PET suspensory ligament group and silk/PET hybrid suspensory ligament group randomly, with 7 dogs in each. The dogs underwent ACL reconstructions in their right knees. At postoperative 6 months, the dogs were sacrificed, and the specimens were evaluated with gross observation, histology, immunohistochemistry, and mechanical testing. The histological and immunohistochemical results showed that the native ACL of the beagle dog held abundant fibroblasts and collagen. The PET-regenerated ligament was loose, and there was a small amount of autologous tissue and collagen. Compared to the PET-regenerated ligament, the silk/PET hybrid-regenerated ligament had a compact structure, and there was more regenerated autologous tissue and collagen. In conclusion, compared to the PET ligament, the silk/PET hybrid ligament kept greater ability to induce the ingrowth of the autologous tissue, indicating that the silk hybrid had enhanced the ligamentization of the PET artificial ligament.

In-body tissue architecture (iBTA), a cell-free, in vivo tissue engineering technology that can produce autologous implantable tissues of the desired shape by subcutaneously embedding specially designed molds, was used to develop long tubular collagenous tissues called Biotubes. Spiral molds for long Biotubes were assembled with an outer pipe-shaped spiral shell and an inner spiral mandrel , and embedded into subcutaneous pouches of beagle dogs or goats for 1 or 2 months. Tubular collagenous tissues were formed at the space between the shell and the mandrel of the mold. Depending on the spiral turn number in the mold, Biotubes of 25 cm or 50 cm (internal diameter 4 mm or 5 mm) were prepared with nearly homogeneous mechanical and histological properties over their entire length. Biotubes stored in 70% ethanol were allogenically implanted into beagle dogs or goats to evaluate their in vivo performance. The 25-cm Biotubes functioned as arterial grafts with no need for luminal modification or mechanical support, and demonstrated vascular reconstruction within 3 months after implantation into dogs. The 50-cm Biotubes functioned as arteriovenous shunt grafts in the neck region of goats without thrombus formation and vascular deformation for 1 month. Thus, the world's longest tissue-engineered vascular grafts with small diameter could be developed using iBTA.

Bacillus coagulans GBI-30, 6086 is a commercially available spore-forming non-toxigenic microorganism approved for use in dog foods with high resiliency to stresses associated with commercial manufacturing. The objectives of this research were to examine the effect of B. coagulans on stool quality, nutrient digestibility, and intestinal health markers in healthy adult dogs. Extruded diets containing graded levels of B. coagulans applied either to the base ration before extrusion or to the exterior of the kibble as a topical coating after extrusion were randomly assigned to 10 individually housed adult beagle dogs (7 castrated males and 3 spayed females) of similar age (5.75 ± 0.23 yr) and body weight (12.3 ± 1.5 kg). The study was designed as a 5 × 5 replicated Latin square with 16-d adaptation followed by 5-d total fecal collection for each period. Five dietary treatments were formulated to deliver a dose of 0-, 6-, 7-, 8-, and 9-log10 colony-forming units (CFU) per dog per day for the control (CON), extruded B. coagulans (PEX), and low, moderate, and high B. coagulans coating levels (PCL, PCM, and PCH), respectively. Food-grade TiO2 was added to all diets at a level of 0.4% to serve as an indigestible dietary marker for digestibility calculations. Data were analyzed using a mixed model through SAS (version 9.4, SAS Institute, Inc., Cary, NC) with treatment as a fixed effect and room (i.e., replicate), period, and dog(room) as random effects. Apparent total tract digestibility of organic matter, crude protein, crude fat, and gross energy calculated by the marker method were numerically greatest for dogs fed the 9-log10 dose treatment with increases (P < 0.05) observed in gross energy and organic matter digestibility compared with the negative control. No significant differences were observed in food intake, stool quality, fecal pH, fecal ammonia, fecal short-chain fatty acids, or branched-chain fatty acids for the extruded B. coagulans treatment (PEX) or the coated B. coagulans treatments (PCL, PCM, and PCH) compared with CON. These results suggest that B. coagulans has a favorable impact on nutrient digestibility and no apparent adverse effects when added to extruded diets at a daily intake level of up to 9-log10 CFU in healthy adult dogs.

Ten healthy Beagle dogs were used to compare selected echocardiographic parameters of right ventricular (RV) systolic function with high field cardiac magnetic resonance imaging (MRI). All dogs underwent complete transthoracic echocardiography before and during anesthesia, as well as cardiac MRI with determination of morphology-based ejection fraction, and phase contrast angiography-derived stroke volume. A correlation analysis was carried out between echocardiographic and MRI parameters. The values of fractional area change, tricuspid annular plane systolic excursion, tissue Doppler imaging derived peak velocity of the isovolumic contraction wave and systolic wave of the lateral tricuspid valve annulus showed lower values under general anesthesia. Of all echocardiographic parameters of RV systolic function, only fractional area change (r = 0.671, P = 0.034) and tissue Doppler imaging derived peak velocity of the systolic wave of the lateral tricuspid valve annulus (r = 0.768; P = 0.01), showed a significant correlation with MRI derived stroke volume. None of the echocardiographic parameters correlated with MRI derived ejection fraction. When evaluating the RV echocardiographically, fractional area change and peak velocity of the systolic wave of the lateral tricuspid valve annulus appear to be the most reliable predictors of RV systolic function when compared to MRI under anesthesia.

An 8-y-old spayed female Beagle dog was presented with peripheral lymphadenomegaly. Lymph node cytology and flow cytometry led to the diagnosis of large B-cell lymphoma (LBCL). We detected minimal percentages of LBCL cells in peripheral blood and bone marrow samples. However, a monomorphic population of neoplastic cells different from those found in the lymph node was found in the bone marrow. T-cell acute lymphoblastic leukemia was suspected based on flow cytometric immunophenotyping. PCR for antigen receptor rearrangement (PARR) revealed clonal rearrangement of both B-cell and T-cell receptors, and the presence of both neoplastic clones in the lymph node, peripheral blood, and bone marrow. The dog was treated with multi-agent chemotherapy but died 46 d following diagnosis. Tumor staging and patient classification are needed to accurately establish a prognosis and select the most appropriate therapeutic protocol.

Microbiota plays a prominent role in periodontal disease, but the canine oral microbiota and how dental chews may affect these populations have been poorly studied. We aimed to determine the differences in oral microbiota of adult dogs consuming dental chews compared with control dogs consuming only a diet. Twelve adult female beagle dogs (mean age = 5.31 ± 1.08 yr) were used in a replicated 4 × 4 Latin square design consisting of 28-d periods. Treatments (n = 12/group) included: diet only (CT); diet + Bones & Chews Dental Treats (BC; Chewy, Inc., Dania Beach, FL); diet + Dr. Lyon’s Grain-Free Dental Treats (DL; Dr. Lyon’s, LLC, Dania Beach, FL); and diet + Greenies Dental Treats (GR; Mars Petcare US, Franklin, TN). Each day, one chew was provided 4 h after mealtime. On day 27, breath samples were analyzed for total volatile sulfur compound concentrations using a Halimeter. On day 0 of each period, teeth were cleaned by a veterinary dentist blinded to treatments. Teeth were scored for plaque, calculus, and gingivitis by the same veterinary dentist on day 28 of each period. After scoring, salivary (SAL), subgingival (SUB), and supragingival (SUP) samples were collected for microbiota analysis using Illumina MiSeq. All data were analyzed using SAS (version 9.4) using the Mixed Models procedure, with P < 0.05 considered significant. All dogs consuming chews had lower calculus coverage and thickness, pocket depth and bleeding, plaque thickness, and halitosis compared with CT. In all sites of collection, CT dogs had a higher relative abundance of one or more potentially pathogenic bacteria (Porphyromonas, Anaerovorax, Desulfomicrobium, Tannerella, and Treponema) and lower relative abundance of one or more genera associated with oral health (Neisseria, Corynebacterium, Capnocytophaga, Actinomyces, Lautropia, Bergeyella, and Moraxella) than those fed chews. DL reduced Porphyromonas in SUP and SUB samples. DL and GR reduced Treponema in SUP samples. DL increased Corynebacterium in all sites of collection. BC increased Corynebacterium in SAL samples. DL and GR increased Neisseria in SAL samples. DL increased Actinomyces in the SUB sample. GR increased Actinomyces in SAL samples. Our results suggest that the dental chews tested in this study may aid in reducing periodontal disease risk in dogs by beneficially shifting the microbiota inhabiting plaque and saliva of a dog’s oral cavity. These shifts occurred over a short period of time and were correlated with improved oral health scores.

In periodontitis patients, dysbiosis of the oral microbiota is not only found at clinically diseased periodontal sites but also at clinically healthy periodontal sites, buccal mucosae, tongue, and saliva. The present study evaluated the safety and efficacy of an oral microbiota transplant (OMT) for the treatment of periodontitis in dogs. Eighteen systemically healthy beagle dogs with naturally occurring periodontitis were enrolled in the study and randomly assigned to a test or control group. A 4-y-old, periodontally healthy female beagle dog served as a universal OMT donor. To reduce periodontal inflammation, all dogs received full-mouth mechanical debridement of teeth and mucosae 2 wk before baseline. At baseline, full-mouth mechanical debridement was repeated and followed by adjunctive subgingival and oral irrigation with 0.1% NaOCl. Subsequently, test dogs were inoculated with an OMT from the healthy donor. No daily oral hygiene was performed after OMT transplantation. Adverse events were assessed throughout the observation period. Clinical examinations were performed and whole-mouth oral microbiota samples were collected at week 2, baseline, week 2, and week 12. The composition of oral microbiota samples was analyzed using high-throughput 16S ribosomal RNA gene amplicon sequencing followed by taxonomic assignment and downstream bioinformatic and statistical analyses. Results demonstrated that the intergroup difference in the primary outcome measure, probing pocket depth at week 12, was statistically insignificant. However, the single adjunctive OMT had an additional effect on the oral microbiota composition compared to the full-mouth mechanical and antimicrobial debridement alone. The OMT resulted in an “ecological shift” toward the composition of the donor microbiota, but this was transient in nature and was not observed at week 12. No local or systemic adverse events were observed throughout the study period. The results indicate that OMT may modulate the microbiota composition in dogs with naturally occurring periodontitis and can be applied safely.

The objective of the studies was to determine the route of excretion, faecal or urinary, of the nonsteroidal anti-inflammatory drug (NSAID) robenacoxib (Onsior™) in cats and dogs. The studies employed a two-part crossover design in 4 beagle dogs (2 female and 2 male, age 36-41 months and body weight 9.0-10.3 kg) and a parallel group comparison of two groups each of 3 domestic short-hair cats (2 female and 4 castrated male, age 35-73 months and body weight 3.0-5.7 kg). Animals were administered single doses of 1 (dog) or 2 (cat) mg/kg of [14 C]-robenacoxib by intravenous (IV) and oral routes. Venous blood samples were taken and analysed for robenacoxib concentration. Faeces and urine were collected for 4 (cats) or 7 (dogs) days and analysed for radioactivity. Robenacoxib was eliminated rapidly from blood (≤ 8 hr). In dogs, expressed as the percentage of the administered dose and adjusted so that faecal plus urine recovery was 100%, the mean (SD) excretion in faeces and urine was, respectively, 64.6% (4.30) and 35.4% (4.3) after IV and 66.7% (6.9) and 33.3% (6.9) after oral administration. The respective values in cats, in faeces and urine, were 72.5% (4.6) and 27.5% (4.6) after IV and 78.5% (2.6) and 21.5% (2.6) after oral administration. In conclusion, excretion of systemically available robenacoxib in cats and dogs was mixed via both faeces and urine, but predominately faecal (~64.6% in dogs and ~72.5% in cats) and assumed to be via biliary excretion.

BACKGROUND AND OBJECTIVES: 7-Hydroxymitragynine (7-HMG) is an oxidative metabolite of mitragynine, the most abundant alkaloid in the leaves of Mitragyna speciosa (otherwise known as kratom). While mitragynine is a weak partial μ-opioid receptor (MOR) agonist, 7-HMG is a potent and full MOR agonist. It is produced from mitragynine by the cytochrome P450 (CYP) 3A, a drug-metabolizing CYP isoform predominate in the liver that is also highly expressed in the intestine. Given the opioidergic potency of 7-HMG, a single oral dose pharmacokinetic and safety study of 7-HMG was performed in beagle dogs. METHODS: Following a single oral dose (1 mg/kg) of 7-HMG, plasma samples were obtained from healthy female beagle dogs. Concentrations of 7-HMG were determined using ultra-performance liquid chromatography coupled with a tandem mass spectrometer (UPLC-MS/MS). Pharmacokinetic parameters were calculated using a model-independent non-compartmental analysis of plasma concentration-time data. RESULTS: Absorption of 7-HMG was rapid, with a peak plasma concentration (C(max), 56.4 ± 1.6 ng/mL) observed within 15 min post-dose. In contrast, 7-HMG elimination was slow, exhibiting a mono-exponential distribution and mean elimination half-life of 3.6 ± 0.5 h. Oral dosing of 1 mg/kg 7-HMG was well-tolerated with no observed adverse events or significant changes to clinical laboratory tests. CONCLUSIONS: These results provide the first pharmacokinetic and safety data for 7-HMG in the dog, and therefore contribute to the understanding of the putative pharmacological role of 7-HMG resulting from an oral delivery of mitragynine from kratom.

Naoxintong Capsule (NXTC), a standardized herbal medicine, has been widely applied in treating cardiovascular and cerebrovascular diseases with remarkable efficacy. However, the efficacy contributing components of NXTC are unclear, and the in vivo absorption and metabolism processes of NXTC remain largely obscured. In this study, using beagle dog as model species, we have identified and tentatively characterized 25 prototype and 15 catabolites of NXTC in beagle dog plasma by ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). We have proposed the in vivo bio-transformation pathways of these absorbed constituents. In addition, for six crucial components, we have developed a quantitative method and conducted plasma pharmacokinetic study of these six components by rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QQQ-MS/MS). In conclude, our study provided comprehensive insights into the understanding of the plasma absorbed components profiling of NXTC as well as their in vivo transformation behaviors, which would be of great value for identifying efficacy contributing critical components as well as mechanism related investigations of NXTC in the future.

An Algal Oil Containing EPA and DHA (AOCED) at ~50% was developed as a sustainable source of omega-3 fatty acids. AOCED was incorporated into extruded dry foods for dogs at 0, 0.75%, 1.5% and 3.0% levels (equivalent to 0, 7.5, 15 and 30 g/kg diet) on dry matter basis at the expense of chicken fat and fed to healthy female Beagle dogs starting at mating and throughout gestation and lactation. The offspring were fed their maternal corresponding diets for 26 weeks after weaning. AOCED-enriched diets were well tolerated by dogs in both generations and did not affect their overall health, physiological parameters, food consumption, body weights and body weight gains. There were no changes in hematology, clinical chemistry, and coagulation parameters in both generations of dogs fed the AOCED diets when compared to those in the control group. Plasma levels of DHA and EPA increased significantly and generally dose-dependently in both generations. The study demonstrated the safety of AOCED in dogs during gestation, lactation, and growth periods at dietary levels up to 3.0wt%, equivalent to 30 g/kg diet. AOCED's bioavailability as a source of DHA and EPA in dogs was demonstrated by the increased plasma concentrations of these nutritional lipids.

Background Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. This study was designed to evaluate the subchronic toxicity of ethanamizuril in beagle dogs at doses of 12, 60 or 300 mg/kg/day in diet for 90 days. Results Ethanamizuril was well tolerated at low and middle dosages in beagle dogs, and no drug-related toxical effects were observaed in terms of survival, clinical observations, organs weight and damage in these dose groups. However, in high dose administration group, food consumption and histologic changes in kidneys were noticed in both sexes of beagle dog, although the renal lesions were finally resolved at the end of 4 weeks exposure of ethanamizuril. Conclusions No-observed-adverse-effect level (NOAEL) was considered for ethanamizuril at dose of 60 mg/kg/day in Beagle dog. This result added toxicity effects of ethanamizuril to the safety database, which might guide safely using of ethanamizuril as a novel coccidiostat.

QXOH-Levobupivacaine (LB) is a fixed-dose combination of 35-mM QXOH and 10-mM LB. It was developed for perioperative analgesia because of its long-acting analgesic effect. The purpose of this study was to evaluate the potential toxicity of QXOH-LB in beagle dogs in accordance with the Guidance on the repeated-dose toxicity published by the China Food and Drug Administration. Groups of five male and five female beagle dogs received normal saline, QXOH-LB (2, 4, and 8 mg/kg, calculated as QXOH), QXOH (2, 4, and 8 mg/kg), or LB (2 mg/kg, equals the concentration of LB in 8-mg/kg QXOH-LB group) at the volume of 1 mL/kg once per day for 14 days through subcutaneous injection. No mortality was observed. Dogs in the control group as well as animals treated with 2-mg/kg QXOH or QXOH-LB exhibited normal behaviors. Clinical signs of toxicity in dogs treated with 4 and 8 mg/kg of QXOH or QXOH-LB included decreased activity, unsteady gait, jerks, tremors, vocalization, emesis, ataxia, lateral/sternal recumbency, deep/rapid respiration, and gasping. Additionally, neurological function was found to be affected by QXOH and QXOH-LB at the doses of 4 and 8 mg/kg. All clinical signs were recovered within 24 h. The no-observed-adverse-effect level of QXOH and QXOH-LB was considered to be 2 mg/kg. Toxicokinetic data showed that exposure to QXOH and LB increased as QXOH-LB doses were increased from 4 to 8 mg/kg. There was no evidence of drug accumulation or any effect of gender.

Introduction: Corrected QT (QTc) interval is an essential proarrhythmic risk biomarker, but recent data have identified limitations to its use. The J to T-peak (JTp) interval is an alternative biomarker for evaluating drug-induced proarrhythmic risk. The aim of this study was to evaluate pharmacological effects using spatial magnitude leads and DII electrocardiogram (ECG) leads and common ECG confounders (ie, stress and body temperature changes) on covariate adjusted QT (QTca), covariate adjusted JTp (JTpca), and covariate adjusted T-peak to T-end (Tpeca) intervals. Methods: Beagle dogs were exposed to body hyper- (42 °C) or hypothermic (33 °C) conditions or were administered epinephrine to assess confounding effects on heart rate corrected QTca, JTpca, and Tpeca intervals. Dofetilide (0.1, 0.3, 1.0 mg/kg), ranolazine (100, 140, 200 mg/kg), and verapamil (7, 15, 30, 43, 62.5 mg/kg) were administered to evaluate pharmacological effects. Results: Covariate adjusted QT (slope −12.57 ms/°C) and JTpca (−14.79 ms/°C) were negatively correlated with body temperature but Tpeca was minimally affected. Epinephrine was associated with QTca and JTpca shortening, which could be related to undercorrection in the presence of tachycardia, while minimal effects were observed for Tpeca. There were no significant ECG change following ranolazine administration. Verapamil decreased QTca and JTpca intervals and increased Tpeca, whereas dofetilide increased QTca and JTpca intervals but had inconsistent effects on Tpeca. Conclusion: Results highlight potential confounders on QTc interval, but also on JTpca and Tpeca intervals in nonclinical studies. These potential confounding effects may be relevant to the interpretation of ECG data obtained from nonclinical drug safety studies with Beagle dogs.

The objective of this study was to determine the minimum requirement (MR) for methionine (Met), when cyst(e)ine (Cys) is provided in excess, in adult dogs of three different breed sizes using the indicator amino acid (AA) oxidation (IAAO) technique. In total, 12 adult dogs were used: 1 neutered and 3 spayed Miniature Dachshunds (4.8 ± 0.4 kg body weight [BW], mean ± SD), 4 spayed Beagles (9.5 ± 0.7 kg BW, mean ± SD), and 4 neutered Labrador Retrievers (31.8 ± 1.7 kg BW, mean ± SD). A deficient Met basal diet with excess Cys was formulated. Dogs were fed the basal diet randomly supplemented with different Met-Alanine (Ala) solutions to achieve final Met concentrations in experimental diets of 0.21%, 0.26%, 0.31%, 0.36%, 0.41%, 0.46%, and 0.66% (as-fed basis). After 2 d of adaptation to the experimental diets, dogs underwent individual IAAO studies. During the IAAO study day, the total feed was divided into 13 equal meals; at the sixth meal, dogs were fed a bolus of l-[1-13C]-phenylalanine (Phe), and thereafter, l-[1-13C]-Phe was supplied with every meal. The total production of 13CO2 during isotopic steady state was determined by the enrichment of 13CO2 in breath samples, and the total production of CO2 measured using indirect calorimetry. The mean MR for Met and the upper 95% confidence limit (CL) were determined using a two-phase linear mixed-effects regression model. For Miniature Dachshunds, the MR for Met was between the first two dietary Met concentrations and is, therefore, between 35.7 and 44.1 mg.kg BW−1·d−1 (0.21% to 0.26%, as-fed basis; no requirement could be determined on a metabolic BW basis). For Beagles and Labrador Retrievers, the MR for Met was 57.5 and 50.4 mg.kg BW−1·d−1, 107.7 and 121.8 mg/kg BW^0.75, or 0.338 and 0.360%, respectively (as-fed basis). The upper 95% CL of Met requirements was 77.9 and 72.4 mg.kg BW−1·d−1, 147.8 and 159.6 mg/kg BW^0.75,or 0.458 and 0.517% for Beagles, and Labradors, respectively (as-fed basis). When pooling data from Beagles and Labrador Retrievers, the MR and upper 95% CL were 56.0 and 75.8 mg.kg BW−1·d−1 or 118.4 and 150.5 mg/kg BW^0.75 or 0.360% and 0.482% (as-fed basis). In conclusion, the MR and the upper 95% CL for Met are different for Dachshunds when compared with Beagles and Labrador Retrievers. Using this low-protein diet, the estimated upper 95% CL Met requirement for Beagles and Labrador is higher than those recommended in the National Research Council (NRC), but NRC is similar to the estimated upper 95% CL for Dachshunds.

Background Mosquitoes are vectors of several pathogens of considerable importance to humans and companion animals, including nematode helminths such as Dirofilaria immitis and Dirofilaria repens that cause heartworm disease and subcutaneous dirofilariosis, respectively. In addition to mosquito-borne pathogen transmission, mosquito bites can cause discomfort and irritation in pets, and even lead to severe hypersensitivity reactions. In the present study, we report an acute local hypersensitivity reaction in a dog following experimental exposure to Aedes (Stegomyia) aegypti. Case presentation A healthy six-year-old male beagle was included in an efficacy study in which dogs (n = 28) were exposed to Ae. aegypti mosquitoes. On Day − 6, the dog was allocated to one of the study groups, consisting of seven dogs to be treated on Day 0 with an imidacloprid/flumethrin collar. After sedation, animals were exposed to approximately 50 females of Ae. aegypti for 60 (± 5) minutes on Days − 6, 1, 7, 14, 21, 28, 55, and 83. On Day − 6, no allergic reaction to the mosquito bites was observed. However, on Day 1, corresponding to the second challenge, the dog demonstrated an acute allergic reaction characterized by swelling of the face (especially in the base of the muzzle and around the eyes), redness of the eyes, and conjunctival edema of the right eye was also observed. The dog was immediately treated with an intramuscular injection of a commercially available antihistamine treatment, Pen-Hista-Strep® containing a suspension of benzylpenicillin, chlorphenamine, dexamethasone, dihydrostreptomycin, and procaine at a dosage of 1 mL per 10 kg. A few hours after treatment, the dog showed noticeable improvement. Conclusions This case provides the first evidence of canine acute local hypersensitivity reaction to mosquito bites under laboratory conditions. This observation suggests that invasive mosquito species such as Aedes spp. may affect the health and comfort of our companion animals, especially for pets with outdoor access without individual protective measures against insect bites.

Objective To evaluate the effects of dexmedetomidine alone or in combination with different opioids on intraocular pressure (IOP) in dogs. Study design Experimental, prospective, crossover, randomized, blinded study. Animals A total of six Beagle dogs (two males and four females) aged 2 years and weighing 15.9 ± 2.9 kg (mean ± standard deviation). Methods Dogs were distributed randomly into seven treatments (n = 6 per treatment) and were administered dexmedetomidine alone (10 μg kg–1; Dex) or in combination with butorphanol (0.15 mg kg–1; DexBut), meperidine (5 mg kg–1; DexMep), methadone (0.5 mg kg–1; DexMet), morphine (0.5 mg kg–1; DexMor), nalbuphine (0.5 mg kg–1; DexNal) or tramadol (5 mg kg–1; DexTra). All drugs were administered intramuscularly. IOP was measured before drug injection (time 0, baseline) and every 15 minutes thereafter for 120 minutes (T15–T120). Results There were significant reductions in IOP compared with baseline in treatments Dex and DexMep at times T30–T120, and in treatment DexMet at T15–T90. IOP decreased compared with baseline in treatments DexBut, DexNal and DexTra at all evaluation times. No changes in IOP were seen in treatment DexMor. The mean IOP values in treatment DexMet at T105–T120 were higher than those for other treatments. Conclusions and clinical relevance Dexmedetomidine alone or in combination with butorphanol, meperidine, methadone, nalbuphine or tramadol resulted in decreased IOP for 120 minutes in dogs. The magnitude of the reduction was small and lacked clinical significance.

Two trials were conducted to assess the acceptance, safety and digestibility of diets containing various inclusion levels of partially defatted black soldier fly (Hermetia illucens) larvae (BSFL) meal and BSFL oil by dogs. In trial 1, 5 extruded diets were evaluated for acceptance in adult Beagle dogs (n = 20; 10 male, 10 female) during a 48-hr period. Diets contained graded levels of BSFL meal (5.0%, 10.0%, and 20.0%), or graded levels of BSFL oil (2.5% and 5.0%), and all diets were well accepted. Thus, a digestibility trial (trial 2) was run with 56 adult dogs (16 male, 40 female) allocated into 7 dietary treatments; dogs were offered an extruded control diet containing no BSFL meal or oil, or extruded diets where BSFL meal partially replaced poultry by-product meal and corn meal at dietary levels of 5%, 10%, or 20% inclusion, or diets with BSFL oil partially replacing poultry fat at a 1:1 ratio at levels of 1%, 2.5%, or 5% inclusion. The treatment diets were fed for 28 d, during which time dogs were monitored for health (via physical examinations, clinical observations, and blood chemistry and hematology) and ingredient evaluation (via body weight, feed consumption, stool observation, and fecal nutrient apparent total tract digestibility). There were no significant differences in body weight or food consumption between treatment groups (P > 0.05) and daily observations indicated that the general health of the animals was maintained throughout the study. Stool quality was maintained at 3.2 to 3.4 (on a 5-point scale with a score of 1 being watery diarrhea and a score of 5 being hard, dry, and crumbly) per treatment group over the fecal observation period (days 22 to 27), indicating a well formed, sticky stool. All group mean hematology and blood chemistry parameters remained within normal limits for dogs. Apparent total tract digestibility of dry matter, protein, fat, and calories was not affected by treatment (P > 0.05). In general, amino acid digestibility was not impacted by treatment although some minor changes were observed. Apparent total tract digestibility was high for all nutrients examined. Overall, it was concluded that BSFL meal and BSFL oil are well tolerated by dogs and their consumption results in no impact to physiology that would be concerning. Based on these data, BSFL meal and oil did not affect general health and could be included safely in dog diets.

Periodontal disease (PD) is the most common clinical condition occurring in adult dogs. The objective of this study was to evaluate the benefits of daily dental chew administration on oral health outcomes in adult dogs. Twelve adult (mean age = 5.31 ± 1.08 yr; mean BW = 13.12 ± 1.39 kg) female beagle dogs were used in a replicated 4 × 4 Latin square design consisting of 28-d periods. On day 0 of each period, teeth were cleaned by a veterinary dentist blinded to treatments. Teeth then were scored for plaque, calculus, and gingivitis by the same veterinary dentist on day 28 of each period. Breath samples were measured for malodor (volatile sulfur compounds) on days 1, 7, 14, 21, and 27 of each period. All dogs consumed the same commercial dry diet throughout the study. Control dogs were offered the diet only (CT), while treatment groups received the diet plus one of three dental chews. Two novel chews (Bones & Chews Dental Treats [BC]; Chewy, Inc., Dania Beach, FL and Dr. Lyon’s Grain-Free Dental Treats [DL]; Dr. Lyon’s, LLC, Dania Beach, FL) and a leading brand chew (Greenies Dental Treats [GR]; Mars Petcare US, Franklin, TN) were tested. Each day, one chew was provided 4 h after mealtime. All tooth scoring data were analyzed using the Mixed Models procedure of SAS (version 9.4; SAS Institute, Cary, NC). Halimeter data were analyzed using repeated measures using the Mixed Models procedure of SAS and testing for differences due to treatment, time, and treatment * time interaction. Data are reported as LS means ± SEM with statistical significance set at P < 0.05. DL performed at the same level as the leading brand, GR, as both resulted in lower (P < 0.05) plaque coverage and thickness scores, calculus coverage scores, and day 27 volatile sulfur concentrations compared with CT. Additionally, DL reduced (P < 0.05) volatile sulfur compounds on day 14 when compared with CT. BC reduced (P < 0.05) calculus coverage and day 27 volatile sulfur concentrations compared with CT. Our results suggest that the dental chews tested in this study may help slow the development and/or progression of PD in dogs.

Black ginseng (BG) has better health benefits than white ginseng. The intake of BG changes the levels of metabolites, such as amino acids, fatty acids, and other metabolites. However, there is no research on the effect of BG extract intake on the metabolic profile of dog serum. In this study, serum metabolic profiling was conducted to investigate metabolic differences following the intake of BG extracts in beagle dogs. The beagle dogs were separated into three groups and fed either a regular diet (RD, control), RD with a medium concentration of BG extract (BG-M), or RD with a high concentration of BG extract (BG-H). Differences were observed among the three groups after the dogs ingested the experimental diet for eight weeks. The concentrations of alanine, leucine, isoleucine, and valine changed with the intake of BG extracts. Furthermore, levels of glycine and &beta, alanine increased in the BG-H group compared to the control and BG-M groups, indicating that BG extracts are associated with anti-inflammatory processes. Our study is the first to demonstrate the potential anti-inflammatory effect of BG extract in beagle dogs. Glycine and &beta, alanine are proposed as candidate serum biomarkers in dogs that can discriminate between the effects of ingesting BG-H.

Quantitative analysis of urethral size in male dogs by retrograde CT urethrography using a power injector is a recently reported technique. The aim of the current, prospective, analytical study was to apply the same method to six, healthy, intact female Beagle dogs. The proximal (P