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Objective To evaluate the agreement between oscillometric blood pressure (OBP) measured from the tongue and invasive blood pressure (IBP), and to compare OBPs measured from the tongue with OBPs measured from the pelvic limb and tail. Study design Prospective experimental study. Animals A total of eight adult Beagle dogs weighing 11.1 ± 1.2 kg. Methods Animals were premedicated with intravenous (IV) acepromazine (0.005 mg kg−1). Anesthesia was induced with alfaxalone (3 mg kg−1) IV and maintained with isoflurane. The dorsal pedal artery was catheterized for IBP measurements. Systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressure were simultaneously measured from the tongue, pelvic limb and tail. Based on invasive SAP, hypertension (>140 mmHg), normotension (90–140 mmHg) and hypotension ( Results Regardless of cuff placement, the mean bias ± standard deviation between IBP and OBP met veterinary (≤10 ± 15 mmHg) and human ( Conclusions and clinical relevance The tongue is a clinically useful site for measuring OBP in anesthetized Beagle dogs, providing reliable estimates of MAP and DAP. The tongue could replace other cuff placement sites and may be a relatively suitable site for assessing hypotension.

Granular-shaped carbonate apatite (CO3Ap) bone substitute has demonstrated good clinical results, especially in the bone augmentation procedure, because it has high osteoconductivity and can be replaced by a new bone. This study aimed to evaluate the potential usefulness of CO3Ap bone substitute for alveolar ridge preservation of beagle dogs during the 9-week follow-up period after surgery. Reconstruction of extraction sockets with CO3Ap granules (CO3Ap group) allowed approximately 1.0 mm higher alveolar bone height than that with a blood clot (control group) at 4 and 9 weeks after surgery. Additionally, the measured area at the buccal aspect of the alveolar bone in the CO3Ap group was approximately 2 mm2 larger than that in the control group at 4 and 9 weeks after surgery. Continuity from the buccal side to palatal side of the alveolar bone was restored, maintaining its contour at 4 weeks after surgery. The amount of bony tissue, especially the amount of mature bone, in the alveolar part was statistically larger than that of control group at 9 weeks after surgery even though complete replacement of CO3Ap granules with new bone was not observed within 9 weeks. In conclusion, CO3Ap granules have good potential for alveolar ridge preservation.

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.

Objective To describe a novel in-plane ultrasound (U/S)-guided temporal approach to peribulbar block in dogs. Study Design Prospective experimental cadaver study. Animals A group of 10 Beagle cadavers. Methods After describing the U/S anatomy, peribulbar injection was performed bilaterally in 10 thawed Beagle cadavers by two randomly assigned operators. A 5–8 MHz microconvex U/S probe was positioned caudal to the orbital ligament in the longitudinal plane. Using an in-plane technique, methylene blue dye was injected in five dogs (10 eyes total), while methylene blue dye and iohexol contrast mixture (50:50) were injected in the remaining five dogs. Injection volume was 0.2 mL cm−1 of cranial length. A computed tomography (CT) scan was performed on dogs injected with dye and contrast to identify spread of contrast. Dissection to visualize dye spread in the orbit was performed in all dogs. Injection success was defined as spread of contrast into the peribulbar space. The pattern of distribution of contrast-dye was also assessed. Comparisons between operator and bilateral injections were assessed using a Student t test (p Results Peribulbar spread was noted in 19/20 injections (95%) on dissection. CT imaging (five dogs) illustrated peribulbar contrast spread in 9/10 injections (90%), with mixed peribulbar/retrobulbar spread for the remaining injection. Contrast was present at the rostral alar foramen in 4/10 (40%) injections, orbital fissure in 5/10 (50%), oval foramen in 1/10 (10%), maxillary nerve in 3/10 (30%) and intracranial in 5/10 (50%). Coverage of the maxillary nerve was noted on 3/20 (15%) injections on dissection. No further dye spread was noted. Conclusions and clinical relevance This technique demonstrated peribulbar spread of injectate in 100% of injections for the 10 canine cadavers studied. Further studies are required to evaluate this technique clinically.

The aim of this pilot study was to evaluate the effect of the timing of postoperative orthodontic force application on bone remodeling during tooth movement into surgical alveolar defects with bone grafts in beagle dogs.Six beagle dogs underwent surgery for buccal dehiscence-type defects (width, 5 mm; height, 6 mm) on the distal root of maxillary second premolars bilaterally for 12 defects. After 1-month healing, bone-augmentation procedures were undertaken at the dehiscence defects. The second premolars were protracted buccally for 6 weeks into the surgical sites immediately (F-0), at 4 weeks (F-4), or 8 weeks (F-8) after grafting. Orthodontic tooth movement was monitored using digital models. Remodeling of alveolar bone was evaluated by histology, histomorphometry, immunohistochemistry, microcomputed tomography, and fluorescence microscopy.Group F-0 showed significant expansion (mean, 2.42 mm) and tipping (mean, 9.03°) after completing orthodontic tooth treatment. The vertical bone defect was significantly lower in groups F-4 and F-8 than that in group F-0 (mean, 2.1, 2.7, and 4.5 mm, respectively). In group F-4, the formation of new bone and mineralization were significantly greater than those in groups F-0 and F-8 (P 0.05). Group F-4 showed a minimal amount of bone-material remnants. Immunohistochemistry showed the highest expression of collagen-1 and osteopontin in group F-4, followed by group F-8 and group F-0, which demonstrated high osteoblast activity and enhanced bone remodeling in group F-4.Orthodontic force application at 4 weeks after an augmentation procedure provided the best functional stimulation for an alveolar bone graft. This strategy enhanced new-bone regeneration and degradation of bone substitutes and, eventually, promoted bone remodeling in the bone-grafted area.

Objective To describe an approach for ethmoidal nerve block (EBLOCK) and to compare the effects of a maxillary nerve block (MBLOCK), EBLOCK and their combination (M-EBLOCK) on heart rate (HR), systolic (SAP), mean (MAP), diastolic (DAP) arterial pressures and respiratory rate (fR) during nasal stimulation in dogs. Study design Prospective, blinded, randomized, crossover placebo-controlled study. Animals Beagle dogs (five cadavers, nine live dogs), with a median (interquartile range) weight of 10.5 (10.3–11.0) kg. Methods The accuracy of iohexol injections (each 1 mL) at the maxillary and ethmoidal foramina in cadavers was evaluated using computed tomography. Then, anesthetized dogs were administered four bilateral treatments separated by 1 week, saline or 2% lidocaine 1 mL per injection: injections of saline at the maxillary and ethmoidal foramina (Control), injections of lidocaine at the maxillary foramina and saline at the ethmoidal foramina (MBLOCK), injections of saline at the maxillary foramina and lidocaine at the ethmoidal foramina (EBLOCK) and injections of lidocaine at all foramina (M-EBLOCK). The ventral nasal meatus was bilaterally stimulated using cotton swabs, and HR, SAP, MAP, DAP and fR were continuously recorded. Values for each variable were compared before and after stimulation using Wilcoxon signed-rank test. Changes in variables among treatments were analyzed using Mann–Whitney U and Kruskal–Wallis tests (p ≤ 0.05). Results Computed tomography revealed iohexol distribution around the openings of the target foramina in all cadavers. In living dogs, HR, SAP, MAP, DAP and fR significantly increased after stimulation within each treatment (p Conclusions and clinical relevance Concurrent injections of lidocaine at the maxillary and ethmoidal foramina attenuated HR, arterial pressure and fR responses to nasal stimulation in Beagle dogs.

Objective Treatment of mandibular lesions sometimes leads to the formation of large defects in the bone. Mandible reconstruction using grafted tissue, bone, and/or medical implants is required following the resection of such lesions. However, such grafts may not completely restore the continuity of the mandible. Facial transplantations using allografts are common, but mandibular allotransplantation has not been performed in humans, due to the unstable immune reaction of the complex tissue. In this study, mandibular transplantations performed under the effect of the immunosuppressive agent, FK506, were evaluated in dogs. Methods Mandibular allotransplantations were performed in 21 pairs of sex-blind beagle dogs. The left side of the mandible in the donor dog was transplanted to the left side of the mandible in the recipient dog. The FK506 doses were 0 mg for 3 dog pairs, 0.08 mg/kg/day for 3, 0.12 mg/kg/day for 5, 0.16 mg/kg/day for 5, and 0.32 mg/kg/day for 5 pairs. Twelve weeks after transplantation, the dogs were euthanized. Computed tomography (CT) and histological examinations of the transplanted sides were performed. Results Successful graft acceptance was dependent on immunosuppressive agent doses, and dogs administered more than 0.16 mg/kg/day FK506 showed 100 % survival. However, dogs administered 0.32 mg/kg/day FK506 showed significant weight loss 12 weeks after the surgery. CT findings showed thick mandibular cortical bone in the transplanted sites. Conclusions These results indicate that 0.16 mg/kg/day FK506 was the ideal dose for allotransplantations. Bone hyperplasia was observed in the transplanted sides, but it is not a disadvantage for allotransplantations.

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/objective Thoracic injuries commonly occur after blunt or penetrating trauma, leading to a blowing wound. For thoracic damage control in emergency, we evaluated a novel chest wound treatment device manufactured using expandable material with a one-way valve, and compared it with closed thoracic drainage for first-line treatment of traumatic pneumothorax in a canine model. Methods Twenty beagle dogs (10 males and 10 females) were randomly and equally divided into two groups. After arteriovenous catheterization, an open pneumothorax model was established in the beagle dog using a minimally invasive procedure. The experimental group was treated using our test device, while the control group was treated by closed thoracic drainage. Animal survival, oxygen saturation (SO2), oxygen pressure (PO2), and changes in chest radiograph with reference to open pneumothorax before and after intervention were recorded at 30, 60, and 120 min. Results After a 24-h experimental period, all animals survived. The control group recovered more quickly than the experimental group at 30 min post-trauma. However, the indices were close to normal 120 min after the test device was inserted. During the puncture, chest-wall hemorrhage was stopped by using the device, whereas the control group experienced continual errhysis. The lung had almost re-expanded at the end of the experiment in both groups. The effect of pulmonary re-expansion in the control group was better than that in the experimental group at 120 min. Conclusion The novel expandable one-way valve device is a safe and useful tool for the treatment of open chest trauma in emergency based on our animal experiment.

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.

Canines, which exhibit similar emotional and social processing to humans, are becoming one of the preferred animal models for neuroscience research. Beagles are the most common laboratory canine, thanks to their moderate size, docile nature, and strong immunity. However, there is currently no MRI brain template for the purebred Beagle, which hinders their use in studies involving neuroimaging. Here, we present the Beagle Brain Template (BBT), which consists of high-resolution in vivo T1-weighted and T2-weighted templates, as well as a myelin template, generated from purebred Beagles. We also present a normalized pipeline for mapping individual structure images onto the BBT space. The BBT shows low variation in the tissue probability map and provides descriptive statistics with smaller variability of brain tissue volumes and brain sizes than that of existing templates. This high-resolution purebred canine brain template lays the foundation for future studies aimed at in vivo analyses of the brain structure and function of the Beagle dogs.

Palaeoenvironmental information collected from zooarchaeological (guanaco exploitation) and palynological (pollen and fungal remains) records from Tierra del Fuego and Isla de los Estados allowed us to reconstruct the natural scenarios during the Holocene to better understand the human behavioral patterns and cultural changes. We have seen that changes in subsistence and guanaco exploitation would not have necessarily been synchronous with climatic variations. However, there is evidence of great climatic and environmental variability in the Fuegian Archipelago during the last 6000 years that would have influenced the distribution of the hunter-gatherer societies. In particular, the Little Ice Age (LIA) event could have caused a reorganization of subsistence activities of the hunter-gatherer societies. The stress caused by this severe climatic episode might have changed the availability of the guanaco population over the inland and coastal areas along the Beagle Channel. Indeed, the colder conditions would have significantly impacted on both the animal population and the availability of their food sources. In summary, the guanaco availability decreased under those colder and intense winters, which is clearly reflected in the substantial drop in the zooarchaeological record. Fil: Fernández, Marilén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina Fil: Ponce, Juan Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina. Universidad Nacional de Tierra del Fuego; Argentina Fil: Zangrando, Atilio Francisco Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras; Argentina Fil: Borromei, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Geológico del Sur. Universidad Nacional del Sur. Departamento de Geología. Instituto Geológico del Sur; Argentina Fil: Musotto, Lorena Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Geológico del Sur. Universidad Nacional del Sur. Departamento de Geología. Instituto Geológico del Sur; Argentina Fil: Alunni, Daniela Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina Fil: Vazquez, Martin Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina

Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol (25-OCH3-PPD), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with 25-OCH3-PPD capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of 25-OCH3-PPD. Results: There was no 25-OCH3-PPD–induced systemic toxicity in beagle dogs at any doses. The level of 25-OCH3-PPD at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of 25-OCH3-PPD administrated groups compared to the vehicle control group. There were also no significant differences between 25-OCH3-PPD administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of 25-OCH3-PPD at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. 25-OCH3-PPD is an extremely safe candidate compound for antitumor treatment. Keywords: Beagle dog, Subchronic toxicity, Ginsenoside

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.

The aim of this work was to determine how far the effects of micro-osteoperforations (MOPs) extend within bone by quantifying the damage caused and the short-term bony adaptations that occur in and around the injury site.With the use of a split-mouth design, 34 MOPs (Propel) were randomly placed in the mandibular furcal bone of 13 beagle dogs either 2 or 4 weeks before killing them. The control side received no treatment. Vickers hardness microindentation, microscopic computed tomography, and histologic analyses were performed to evaluate the bone surrounding the MOPs.Microfractures produced during insertion extended ∼0.6 mm from the MOP sites. Cortical and trabecular bone were significantly less dense on the experimental than on the control side up to 4.2 mm from the edge of the MOP, but side differences were small (5%) beyond 1.5 mm from the MOP. Experimental cortical bone was significantly softer than the control bone up to 0.8 mm from the MOP after 2 weeks of healing, and up to 0.5 mm from the MOP after 4 weeks of healing. Hematoxylin and eosin stained sections of cortical and trabecular bone showed small areas of woven bone within the MOP sites after 2 weeks, and acellular areas of bone extending ∼0.5 mm from the MOP. After 4 weeks of healing, there were greater amounts of woven bone, as well as early signs of lamellar bone, in and around the MOP sites. Markedly increased TRAP activity extending up to 2.5 mm from the MOP was evident after 2 weeks, but not after 4 weeks. Vital fluorescence staining showed diffuse bone deposition on the experimental side up to 1.5 mm from the MOP margin.When MOPs are performed in beagle dogs, demineralization is transient and healing of the injured area, as well as remineralization of bone affected by MOP placement, begins during the first 2 weeks. Although the transient effects extend farther, the principal effects extend only ∼1.5 mm from the MOP site.

Objective To evaluate the effect of two doses of fentanyl upon chest wall rigidity of dogs anesthetized at equipotent doses of isoflurane [1.3 minimum alveolar concentration (MACISO) of each dose of fentanyl]. Study design Prospective crossover randomized study. Animals A group of eight male Beagle dogs, approximately 1 year old and weighing 12.1 ± 1.6 kg (mean ± standard deviation). Methods The dogs were anesthetized with isoflurane and instrumented for the measurement of esophageal pressure (PESO), flow ( V ˙ ) and volume ( V ). Chest wall elastance (ECW) was estimated by multiple linear regression of the model. PESO(t) = V ˙ (t) × RCW + V(t) × ECW + EEPESO where t is time, RCW is chest wall resistance and EEPESO is end-expiratory PESO. Chest wall compliance (CCW) was calculated as 1/ECW and normalized to the body weight of each dog (mL cmH2O−1 kg−1). Anesthesia was maintained at 1.3 MACISO for at least 15 minutes and CCW recorded (CCW-ISO). The dogs were randomly assigned to the lower fentanyl dose [loading dose (33 μg kg−1) and infusion (0.2 μg kg−1 minute−1)] or the higher fentanyl dose [loading dose (102 μg kg−1) and infusion (0.8 μg kg−1 minute−1)]. After 60 minutes of fentanyl infusion, CCW was recorded for each dose (CCW-FENT). During fentanyl infusion, the dogs were maintained at equipotent doses of isoflurane (1.3 MACISO for each fentanyl dose). A two-way analysis of variance followed by a Bonferroni test was used to compare CCW-ISO and CCW-FENT in both treatments and CCW-FENT between treatments. A p value Results Neither of the fentanyl doses decreased CCW and there was no difference in CCW-FENT between doses. Conclusions and clinical relevance Fentanyl at the studied doses did not result in chest wall rigidity in dogs anesthetized with equipotent doses of isoflurane (1.3 MACISO).

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.

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.

Beagle dog is a standard animal model for evaluating nonclinical pharmacokinetics of new drug candidates. Glucuronidation in intestine and liver is an important first-pass drug metabolic pathway, especially for phenolic compounds. This study evaluated the glucuronidation characteristics of several 7-hydroxycoumarin derivatives in beagle dog's intestine and liver in vitro. To this end, glucuronidation rates of 7-hydroxycoumarin (compound 1), 7-hydroxy-4-trifluoromethylcoumarin (2), 6-methoxy-7-hydroxycoumarin (3), 7-hydroxy-3-(4-tolyl)coumarin (4), 3-(4-fluorophenyl)coumarin (5), 7-hydroxy-3-(4-hydroxyphenyl)coumarin (6), 7-hydroxy-3-(4-methoxyphenyl)coumarin (7), and 7-hydroxy-3-(1H-1,2,4-tirazole)coumarin (8) were determined in dog's intestine and liver microsomes, as well as recombinant dog UGT1A enzymes. The glucuronidation rates of 1, 2 and 3 were 3–10 times higher in liver than in small intestine microsomes, whereas glucuronidation rates of 5, 6, 7 and 8 were similar in microsomes from both tissues. In the colon, glucuronidation of 1 and 2 was 3–5 times faster than in small intestine. dUGT1A11 glucuronidated efficiently all the substrates and was more efficient catalyst for 8 than any other dUGT1A. Other active enzymes were dUGT1A2 that glucuronidated efficiently 2, 3, 4, 5, 6 and 7, while dUGT1A10 glucuronidated efficiently 1, 2, 3, 4, 5 and 7. Kinetic analyses revealed that the compounds’ Km values varied between 1.1 (dUGT1A10 and 2) and 250 µM (dUGT1A7 and 4). The results further strengthen the concept that dog intestine has high capacity for glucuronidation, and that different dUGT1As mediate glucuronidation with distinct substrates selectivity in dog and human. peerReviewed

Objective To evaluate endotracheal tube intracuff pressure (Pcuff) changes over time and the effect of these changes on air leak pressure (Pleak). Study design Prospective experimental study. Animals A group of nine healthy adult Beagle dogs. Methods In part I, in vitro measurements of Pcuff were recorded for 1 hour in eight endotracheal tubes subjected to four treatments: room temperature without lubricant (RT0L), room temperature with lubricant (RTWL), body temperature without lubricant (BT0L), and body temperature with lubricant (BTWL). In part II, nine dogs were endotracheally intubated and Pleak was evaluated at Pcuff of 25 mmHg. Subsequently, Pcuff was reset to 25 mmHg (baseline) and Pcuff measurements were recorded every 5 minutes for 1 hour. Subsequently, a second Pleak measurement was recorded at the current Pcuff. The data were analyzed using Wilcoxon signed-rank test, repeated measures anova and Mann–Whitney U test. Results In part I, Pcuff differed significantly between the RT0L and RTWL treatments at 5–60 minutes, and between the BT0L and BTWL treatments at 5–35, 55 and 60 minutes (p Conclusions and clinical relevance Significant decreases in Pcuff over time were measured. Pleak may decrease during anesthesia and increase the risk for silent pulmonary aspiration. The results indicate the need for testing Pcuff more than once, especially at 10 minutes after the onset of anesthesia.

Complement-mediated intravascular hemolysis occurs in canine immune-mediated hemolytic anemia (IMHA). Complement inhibitors such as recombinant C1 esterase inhibitor (rC1-INH) might prevent this process and alter the disease course. This study aimed to characterize the pharmacokinetics of a single 500 IU IV dose of rC1-INH in 8 healthy beagle dogs, evaluate the dogs for any adverse effects of drug administration, and determine whether rC1-INH administration induces anti-drug antibody formation. Serum rC1-INH concentrations were measured using a commercial functional ELISA at baseline and at 10, 20, 40, 60, 80, 100, 120, 240, 360, 480, 600, 720, 960, and 1440 min post drug administration. Complete blood counts were conducted at baseline, 720 and 1440 min. Western blot analysis, using rC1-INH as the target antigen was used to detect anti-drug antibodies in 14-day serum samples. No adverse clinical reactions were noted following rC1-INH administration. Pharmacokinetic modelling suggested that the peak C1-INH concentration achieved is 0.21 IU/mL and that C1-INH concentration is significantly greater than baseline for 100 min following injection. A robust antibody response was detected which suggests that rC1-INH should not be re-administered after an initial course. Clinical trials of rC1-INH in dogs with intravascular IMHA are now warranted.

As important companion animals, dogs may serve as intermediate hosts for transmitting influenza virus to humans. However, knowledge regarding H3N2 canine influenza virus (CIV) pathogenicity is not comprehensive, which directly affects the animal models of pathogenicity in H3N2 CIV vaccine research. Here, to assess H3N2 CIV pathogenicity, we utilized 30 ten-week-old purpose-bred beagles intratracheally or intranasally inoculated with 106 50% egg-infectious dose. Intratracheal inoculation was more virulent to dogs than intranasal inoculation as shown by lung pathology score, histopathological changes, clinical symptoms, and body temperature. More intense virus replication was observed in the upper and lower respiratory tracts by intratracheal than intranasal inoculation according to nasal swabs, various organ virus titers, and antigen expression. These results may enhance the H3N2 CIV infection model, providing a more complete experimental basis for studying intrinsic H3N2 CIV pathogenic mechanism, and also serving a reference role for CIV prevention and treatment.

Dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI) consists of acquisition of native baseline images, followed by a series of acquisitions performed during and after administration of a contrast medium. DCE-MRI, in conjunction with hepatobiliary-specific contrast media, such as gadoxetic acid (GD-EOB-DTPA), allows for precise characterisation of the enhancement pattern of the hepatic parenchyma following administration of the contrast agent. The aim of the study was to assess the pattern of temporal resolution contrast enhancement of the hepatic parenchyma following administration of GD-EOB-DTPA and to determine the optimal time window for post-contrast assessment of the liver. The study was carried out on eight healthy beagle dogs. MRI was performed using a 1.5T scanner. The imaging protocol included T1 weighted (T1-W) gradient echo (GRE), T2 weighted (T2-W) turbo spin echo (TSE) and dynamic T1-W GRE sequences. The dynamic T1-W sequence was performed using single 10mm thick slices. Regions of interest (ROIs) were chosen and the signal intensity curves were calculated for quantitative image analysis. The mean time to peak for all dogs was 26min. The plateau phase lasted on average 21min. A gradual decrease in the signal intensity of the hepatic parenchyma was observed in all dogs. A DCE-MRI enhancement pattern of the hepatic parenchyma was evident in dogs following the administration of a GD-EOB-DTPA, establishing baseline data for an optimal time window between 26 and 41min after administration of the contrast agent.

To compare the effects of alfaxalone and propofol, with and without acepromazine and butorphanol followed by doxapram, on laryngeal motion and quality of laryngeal examination in dogs.Randomized, crossover, blinded study.Ten female Beagle dogs, aged 11-13 months and weighing 7.2-8.6 kg.The dogs were administered four intravenous (IV) treatments: alfaxalone (ALF), alfaxalone+acepromazine and butorphanol (ALF-AB), propofol (PRO) and propofol+AB (PRO-AB). AB doses were standardized. Dogs were anesthetized 5 minutes later by administration of alfaxalone or propofol IV to effect. Arytenoid motion during maximal inspiration and expiration was captured on video before and after IV doxapram (0.25 mg kgA 20% increase in RGSA was the minimal arytenoid motion that was detectable. RGSA was significantly less in ALF before doxapram compared with all other treatments. A20% increase in RGSA was measured in eight of 10 dogs in PRO and in all dogs in ALF before doxapram. After doxapram, RGSA was significantly increased for PRO and ALF; however, 20% of dogs in PRO and 50% of dogs in ALF still had20% increase in RGSA. A20% increase in RGSA was measured in five of 10 dogs in PRO-AB and ALF-AB before doxapram. All dogs in PRO-AB and ALF-AB with20% increase in RGSA before doxapram had ≥20% increase in RGSA after doxapram. Examination quality was significantly better in PRO-AB and ALF-AB.The use of acepromazine and butorphanol improved the quality of laryngeal examination. Any negative impact on arytenoid motion caused by these premedications was overcome with doxapram. Using either propofol or alfaxalone alone is not recommended for the evaluation of arytenoid motion.

The safety of 3′-sialyllactose (3′-SL) sodium salt was evaluated by testing for gene mutations, in vivo and in vitro clastogenic activity, and animal toxicity in beagle dogs and rats. The results of all mutagenicity and genotoxicity tests were negative, indicating that 3′-SL does not have any mutagenic or clastogenic potential. The mean lethal dose (LD50) of 3′-SL sodium salt was well above 20 g/kg body weight (bw) in rats. A dose escalation acute toxicity study in Beagle dogs also indicated no treatment-related abnormalities. Subsequent 28-day and 90-day toxicity studies in Sprague- Dawley (SD) rats involved dietary exposure to 500, 1,000, and 2000 mg/kg bw of 3′-SL sodium salt and a water (vehicle) control. There were no treatment-related abnormalities on clinical observations, body weight, food consumption, behavior, hematology, clinical chemistry, organ weights, relative organ weights, urinalysis parameters, or necropsy and histopathological findings. The No Observed Adverse Effect Level (NOAEL) of 3′-SL sodium salt was determined to be higher than 2000 mg/kg bw/day in an oral subchronic toxicity study in rats, indicating that the substance is an ordinary carbohydrate with the lowest toxicity rating. Results confirm that 3′-SL sodium salt has a toxicity profile similar to other non-digestible carbohydrates and naturally occurring human milk oligosaccharides (HMOs) and support its safety for human consumption in foods.

Cardiovascular disease (CVD) is a class of chronic diseases, and the patients need long-term medication. Propylene glycol alginate sodium sulfate (PGAS) obtained from marine algae, which has been applied to clinical treatments of CVD in China for 30 years. However, none PGAS have been formulated in extended-release tablet. Herein, we developed an extended-release (ER) tablet of PGAS fabricated by wet granulation method using hydroxypropyl methylcellulose (HPMC) to prolong the duration of efficacy. Furthermore, we investigated its in vitro data and in vivo pharmacokinetic characteristics in beagle dogs. The commercial tablets exhibited a rapid release behavior and more than 75% of PGAS was released within 1 h, while 91.09 ± 1.65% of PGAS released from the PGAS ER tablets in 12 h, which followed the non-Fickian diffusion mechanism in vitro. Moreover, the pharmacokinetic profiles of PGAS in beagle dogs emerged a prolonged release of the ER tablets within 48 h. Compared with the commercial tablets, the Tmax, AUC and bioavailability of PGAS ER tablets are markedly increased by 6-fold, 1.71-fold and 2.17-fold, respectively. Such data further demonstrated PGAS ER tablet as a promising agent for treating CVD.

No in vivo study has been reported on the mechanical reinforcement of a tooth after regenerative endodontic treatment (RET). The present work aimed to evaluate the concurrent use of platelet-rich fibrin (PRF) with a blood clot (BC) in RET concerning periapical healing, root development, and tooth structural reinforcement.In our study, 24 premolars from 3 beagle dogs were assigned into control, BC, and PRF + BC groups. Periapical healing was monitored with quantitative measurements of root elongation and thickening radiographically. Tooth biomechanical integrity was assessed with the fracture resistance test. Histologic evaluation was conducted.There was a significant difference among the periapical radiolucency decreasing rate of the control (43.75%) and the BC (100%) and PRF + BC (100%) groups (P .05). The increase of root length and thickness in both the BC and PRF + BC groups was significantly greater than that in the control group (P .05). No significant difference was detected between the 2 experimental groups regarding periapical healing or root development (P .05). Teeth in the BC (249.3 ± 64.1 N) and PRF + BC (281.7 ± 37.8 N) groups had significantly higher fracture resistance than those in the control group (108.5 ± 23.3 N) (P .05). No significant difference was revealed between the BC and PRF + BC groups (P .05). Histologic evidence of cementumlike tissue deposition along the canal wall with scattered bonelike tissue in the canal was observed.Either a combination of PRF with BC or BC alone could improve periapical healing, induce root development, and reinforce tooth structure. No additional benefit of PRF to BC in RET was found.

Microplastics (MPs) have been identified in diverse marine invertebrates; however, there are few studies on limpets. This study aimed to evaluate and compare the presence of MPs in Nacella magellanica among sites of the Beagle Channel with different degree of anthropogenic influence. Intertidal limpets were sampled in three sites: Ushuaia Bay (UB) (inside Ushuaia city), a site with high anthropogenic influence owing to population growth, and fisheries, industrial and port activities; Ensenada Zaratiegui (EZ) and Playa Larga (PL) (west and east of Ushuaia city, respectively), both sites with a certain degree of environmental protection and low anthropogenic influence. MPs were isolated from the whole soft tissue of individuals by oxidative digestions with H2O2 (30%; 1:10 w/v). MPs occurrence was 100% in organisms from UB and EZ, whereas 90% in PL. Limpets from UB showed 10 ± 6.69 MPs/ind and 2.22 ± 0.78 MPs/g ww, while in PL and EZ there were 2.90 ± 2.02 MPs/ind and 0.96 ± 0.94 MPs/g ww; and 5.60 ± 2.59 MPs/ind and 2.41 ± 1.47 MPs/g ww, respectively. Fibres were the most abundant MPs type, followed by fragments and films. Fibres and films were identified as semi-synthetic cellulose and, although the polymer matrix of fragments was masked by copper phthalocyanine, one of them could be identified as polystyrene. As expected, the highest abundance of MPs was found in UB. However, a lower abundance of particles was detected in PL (downstream of UB) than in EZ (upstream of UB). This could be due to the influence of both the main current of the Beagle Channel and fluvial discharges, reducing the buoyancy of MPs. More studies are needed to understand the contribution of regional and local features to the accumulation of MPs in these environments and their interaction with the biota.

The objective of this study was to evaluate the influence of cassava fiber (CA) concentrations and conventional fiber sources on coefficients of total tract apparent digestibility (CTTAD) and metabolizable energy (ME) of the diet, fecal characteristics, intestinal fermentation products, and fecal microbiota of dogs. Seven diets were evaluated: control diet (without the addition of fiber sources); three diets with increasing concentrations of CA: 40, 80, and 120 g/kg (totaling 61, 72, and 83 g/kg of total dietary fiber, TDF, respectively); diet with 38 g/kg of cellulose (CE); diet with 60 g/kg of beet pulp (BP); and diet with 38 g/kg of lignocellulose (LC). Diets with 120 g/kg of CA, CE, BP, and LC contained approximately 80 g/kg of TDF. Diet digestibility, fecal characteristics, intestinal fermentation products, and fecal microbiota were evaluated in 14 adult Beagle dogs, distributed in a randomized block design, with 3 periods of 15 days each. Each 2 dogs were fed one of the diets per period, totaling 6 replicates/treatment at the end of the 3 periods. The CTTAD of organic matter and dry matter was higher (P 0.05). The 120 g/kg CA diet resulted in higher fecal concentrations of acetate and total short-chain fatty acids (SCFA) when compared to the control, CE, and LC diets (P

Cyclocreatine (LUM-001) was evaluated for chronic toxicity (23 weeks) in beagle dogs to support clinical development in patients with creatine transporter deficiency (CTD) disorder. Deionized water (vehicle control) or cyclocreatine was administered by oral gavage twice daily (12±1 hours apart) at 20, 40 and 75 mg/kg/dose followed by a recovery period. Due to severe toxicity, the study was terminated earlier than the planned 39 weeks of dosing. Animals in the 20, 40 and 75 mg/kg/dose groups completed 160, 106, and 55 days of dosing, respectively, followed by 30, 55 and 106 days of a recovery period, respectively. Three (25%), 7 (58%), and 7 (58%) animals were euthanized and/or found dead in the 40, 80, and 150 mg/kg/day dose groups, respectively. Clinical signs observed were inappetence, frequent emesis, stool abnormalities, weight loss, lethargy and respiratory distress. Histopathological evaluation revealed congestion, edema, cellular infiltration, fibrin, and/or hemorrhage in the lungs of all dose groups. Additionally, animals in all cyclocreatine treatment groups had perinuclear cytoplasmic vacuoles in the heart, kidneys, skeletal and smooth muscles. After the recovery period, the vacuoles were still observed in the cardiac and renal tissues. Cyclocreatine was absorbed rapidly with mean T(max) within 1 to 2 hours and half-life ranged between 2.17 to 2.79 hours on Day 1, however, on the final day of dosing, it ranged between 5.80 to 8.77 hours (males) and 10.3 to 13.1 hours (females). To conclude, in this study the lungs, kidneys, heart, skeletal and smooth muscles were identified as the target organs of cyclocreatine toxicity in beagle dogs.

Improving the health and immunity of pets is a concern of the guardians, while maintaining the health of the animals directly impacts the owners' health and public health. The objective of this study was to produce a dog feed containing a microencapsulated phytogenic blend, as well as determine the impact of the additive on animal health and its intestinal microbiota. The composition included microencapsulated thymol, carvacrol, and cinnamaldehyde, at 300 mg/kg of feed. Ten male beagle dogs were divided into two groups, identified as follows: the control group (C; ingested the feed without the additive) and the treated group (T; consumed feed containing the phytogenic blend). The dogs received 300 g of feed/day divided into two meals. Greater neutrophil counts in group T and lymphocyte counts were observed at the end of the experiment, as well as levels of α2-globulins and γ-globulin, while β1 and β2-globulins levels were lower in group T. Serum nitrogen oxide levels were higher in group T. Levels of reactive oxygen species were lower in group T at days 30 and 45, unlike activity of glutathione peroxidase that was higher. We found less bacterial contamination in the feces of dogs in group T, i.e., total bacterial count, total coliform counts, and counts of Salmonella and Escherichia coli were lower on days 30 and 45. Phytogenic blend intake reduces bacterial counts in stool and improves antioxidant/oxidative status and immune responses.

Intramuscular (IM) injection of nitrite (1-10 mg/kg) confers survival benefit and protects against lung injury after exposure to chlorine gas in preclinical models. Herein, we evaluated safety/toxicity parameters after single, and repeated (once daily for 7 days) IM injection of nitrite in male and female Sprague Dawley rats and Beagle dogs. The repeat dose studies were performed in compliance with the Federal Drug Administration's (FDA) Good Laboratory Practices Code of Federal Regulations (21 CFR Part 58). Parameters evaluated consisted of survival, clinical observations, body weights, clinical pathology, plasma drug levels, methemoglobin and macroscopic and microscopic pathology. In rats and dogs, single doses of ≥100 mg/kg and 60 mg/kg resulted in death and moribundity, while repeated administration of ≤30 or ≤ 10 mg/kg/day, respectively, was well tolerated. Therefore, the maximum tolerated dose following repeated administration in rats and dogs were determined to be 30 mg/kg/day and 10 mg/kg/day, respectively. Effects at doses below the maximum tolerated dose (MTD) were limited to emesis (in dogs only) and methemoglobinemia (in both species) with clinical signs (e.g. blue discoloration of lips) being dose-dependent, transient and reversible. These signs were not considered adverse, therefore the No Observed Adverse Effect Level (NOAEL) for both rats and dogs was 10 mg/kg/day in males (highest dose tested for dogs), and 3 mg/kg/day in females. Toxicokinetic assessment of plasma nitrite showed no difference between male and females, with Cmax occurring between 5 mins and 0.5 h (rats) or 0.25 h (dogs). In summary, IM nitrite was well tolerated in rats and dogs at doses previously shown to confer protection against chlorine gas toxicity.

Benzaldehyde and 2-hexanone are allomones produced by beagle dogs that reduce infestation by Rhipicephalus sanguineus sensu lato on these animals and on susceptible dogs which artificially release these repellents. These observations were obtained in previous laboratory tests or artificial infestations of susceptible dogs under controlled conditions. Here we evaluated the efficacy of collars delivering these repellents for suppressing the loads of R. sanguineus s.l. on naturally infested mixed-breed dogs under field conditions. Thirty dogs naturally infested with R. sanguineus s.l. were separated into two groups with 15 dogs each. The dogs from the treatment group received the collars with slow-release formulations of the allomones, and the dogs from the control group received collars without such compounds. Collar effectiveness tests were carried out over 30 days. All ticks found were removed from each dog, identified, and counted every collection day. The density of the different life stages of R. sanguineus s.l. varied greatly between groups and across evaluation times. Adult ticks were the stage most abundant and prevalent on infested dogs. The counts for larvae, nymphs and adults were similar between the control and the treatment groups within each tick collection day. Conversely, when we considered the total number of ticks over 30 days and gathered all life stages collected in the same animal, the dogs from the control group had significantly higher loads (35.3 ± 4.27) of ticks than the dogs from the treatment group (21.8 ± 2.96) (P0.01). In addition, the efficacy of treatment with repellent collars was high for adult ticks (30.8%) but was extremely low for reducing larval or nymphal infestation (0 or 2.6%, respectively). The present study demonstrates, for the first time, the efficacy of these volatile compounds on naturally infested dogs under field conditions. The development of a technologically enhanced device for slow release of the allomones tested here can be an advantageous alternative for reducing R. sanguineus s.l. infestation on dogs in residential environments.

Motivated by conventional medicines' ineffectiveness and the appearance of bacterial resistance, homeopathic medicines are being increasingly demanded by the veterinary market. Dog feces contain high bacterial and pathogenic loads, which can cause diseases in animals and facilitate zoonotic transmission. Adequate animal immunity contributes to the elimination of potential pathogens. This work's objective was to evaluate the effects of using a homeopathic medication on blood cell counts, serum protein levels, and fecal bacterial counts in dogs. Two groups were used, each including five 19-month-old Beagle dogs. The homeopathic product Orgainfecto® was sprayed on the two daily meals in the treated group (T), at 0.5 mL/animal/day for 60 days; the group that did not receive the homeopathic was considered the control (C), who were fed only the vehicle used in the production of the homeopathic as a placebo. On days 1, 30, and 60, individual stool samples were collected for bacterial counts in the stool, blood samples for blood counts, and serum for biochemical tests. Total bacterial counts in feces were lower in group T on days 30 and 60 of the experiment, while total coliforms and E coli. were lower in this group on day 60. Total leukocyte counts were lower on day 60 in group T, unlike the neutrophil count, higher in group T on day 30, and eosinophils on day 60. However, the lymphocyte count was lower in group T on days 30 and 60. There was an increase in globulin and total protein in group T on day 60. We conclude that the tested homeopathic causes neutrophils and eosinophils' stimulation and increases globulins levels even with reduced lymphocytes. The daily consumption of homeopathic by dogs decreases the intestinal bacterial load, resulting in less environmental contamination and animal and human colibacillosis risks.

Hyperlipidemia is described as an increase in serum and/or plasma levels of triglycerides, cholesterol, or both. This disturbance can be primary in some cases, or combined with other comorbidities such as endocrinopathies, liver diseases, or specific drug use. Among the various ways to control dyslipidemia are specific diets, omega-3 fatty acid supplementation, or hypolipemiant treatment. Herbal medicine has been used in the human clinical routine to reduce cholesterol circulation. With an aim to expand its application in veterinary medicine, we analyzed the use of phytosterols in dogs as a potential alternative to control hypercholesterolemia. We performed lipidogram analysis in healthy dogs to examine the possible adverse effects during the treatment. Eight Beagle dogs received orally two 650 mg capsules of phytosterols (Collestra, Ache), for 15 consecutive d, along with the 2 usual meals. All animals remained clinically stable during the trial. There were significant alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels during the trial. LDL was reduced (86.8 ± 29.89 mg/dL [D0], 74.45 ± 31.58 mg/dL [D8], and 58.91 ± 18.65 mg/dL [D15]; P = 0.0442) and HDL was elevated (83.40 ± 12.05 mg/dL [D0], 86.46 ± 13.05 mg/dL [D8], and 101.5 ± 10.52 [D15]; P = 0.0141), while total cholesterol and triglyceride concentrations remained constant and within the normal range for canine species. Thus, a 1300 mg dose of phytosterols, administrated orally and fractionated along with the 2 usual meals, was capable of reducing LDL and increasing HDL concentration in healthy nondyslipidemic dogs, which makes them candidates to be included on the list of hypolipemiant drugs for clinical use in dogs with hypercholesterolemia.

Made available in DSpace on 2018-12-11T17:13:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-11-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective In this study, the presence of the prtC and fimA genes involved in the pathogenicity of oral Porphyromonas spp. isolated from dogs with periodontitis and healthy, as well as their genetic diversity was investigated. Design Thirty-two Beagle dogs, 24 with periodontitis and 8 healthy were evaluated. Subgingival samples from only one gingival site of both groups were collected. Bacteria grown in anaerobiosis were identified by RAPID ID 32A kits. From each strain the respective DNA was obtained and used to genotyping by conventional PCR and AP-PCR. Results Dogs with periodontitis harbored 28 P. gulae, 2 P. creviocaricanis, 1 P. cangingivalis and 7 P. macacae; and from healthy dogs, 11 P. gulae and 5 P. circumdentaria. In P. gulae isolated from periodontal dogs the gene prtC was observed in 19 (67.85%) and in 7 (63.63%) from healthy dogs. P. gulae strains from periodontal dogs harbored either the gene fimA I or fimA II; while strains from healthy dogs harbored the gene fimA I, fimA II, fimA III or fimA IV, as well as 1 P. circumdentaria the gene fimA II. By AP-PCR strains were grouped in different clusters suggesting heterogeneity of these microorganisms. Conclusions The results presented herein inform that Porphyromonas spp. isolated from dogs with and without periodontitis harbored the prtC and fimA genes and it could be a role in the establishment of the infectious process. Anaerobe Laboratory Department of Microbiology Institute of Biomedical Sciences University of Sao Paulo – USP Department of Dental Materials and Prosthodontics School of Dentistry of Araraquara Univ Estadual Paulista – UNESP Department of Dental Materials and Prosthodontics School of Dentistry of Araraquara Univ Estadual Paulista – UNESP FAPESP: 2013/13652-6

Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg-1) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg-1).

Objective To evaluate the effect of two levels of partial neuromuscular block (NMB) on arytenoid abduction, tidal volume (VT) and peak inspiratory flow (PIF) in response to a hypercarbic challenge in anesthetized dogs. Study design Prospective laboratory study. Animals Eleven healthy male Beagle dogs aged 3–5 years. Methods Dogs were anesthetized with propofol and dexmedetomidine infusions. The rima glottidis was observed via an endoscope placed through a laryngeal mask airway. Atracurium infusion was titrated to obtain two levels of partial NMB. The normalized glottal gap area (NGGA; glottal gap area normalized to height squared of rima glottidis) at peak inspiration during a hypercarbic challenge (10% CO2 inspired for 1 minute) was measured at baseline, during mild [train-of-four (TOF) ratio 0.4–0.6] and shallow (TOF ratio 0.7–0.9) NMB, and 30 minutes after spontaneous recovery from NMB. The VT and PIF were measured at the same time points and compared using anova for repeated measures and Tukey’s post hoc tests. Results The NGGA and VT were significantly lower than baseline during both levels of partial NMB with no difference between mild and shallow NMB (p Conclusions and clinical relevance The NGGA and VT at peak inspiration in response to a hypercarbic challenge were reduced during partial NMB block, with decreased abduction of the arytenoid cartilages. This dysfunction was present even at shallow levels of NMB.

Objective To characterize the isoflurane-sparing effects of a high and a low dose of fentanyl in dogs, and its effects on mean arterial pressure (MAP) and heart rate (HR). Study design Prospective, randomized crossover trial. Animals Eight healthy male Beagle dogs weighing 12.1 ± 1.6 kg [mean ± standard deviation (SD)] and approximate age 1 year. Methods Dogs were anesthetized using isoflurane and minimum alveolar concentration (MAC) was determined in duplicate by the bracketing method using an electrical stimulus on the tarsus. Animals were administered fentanyl: low dose (33 μg kg −1 loading dose, 0.2 μg kg −1 minute −1 ) or high dose (102 μg kg −1 loading dose, 0.8 μg kg −1 minute −1 ) and MAC was re-determined (MAC ISO-F ). Blood was collected for analysis of plasma fentanyl concentrations before administration and after MAC ISO-F determination. All values are presented as mean ± SD. Results Isoflurane MAC (MAC ISO ) was 1.30 ± 0.23% in the low dose treatment, which significantly decreased to 0.75 ± 0.22% (average MAC reduction 42.3 ± 9.4%). MAC ISO was 1.30 ± 0.18% in the high dose treatment, which significantly decreased to 0.30 ± 0.11% (average MAC reduction 76.9 ± 7.4%). Mean fentanyl plasma concentrations were 6.2 and 29.5 ng mL −1 for low and high dose treatments, respectively. MAP increased significantly only in the high dose treatment (from 81 ± 8 to 92 ± 9 mmHg). HR decreased significantly in both treatments from 108 ± 25 to 61 ± 14 beats minute −1 with the low dose and from 95 ± 14 to 42 ± 4 beats minute −1 with the high dose. Conclusions and clinical relevance Fentanyl administration resulted in a dose-dependent isoflurane MAC-sparing effect with bradycardia at both doses and an increase in MAP only at high dose. Further evaluation is needed to determine the effects of fentanyl on the overall cardiovascular function.

Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines.

The present study aimed to evaluate the influence of whole-body vibration (WBV) exercise on hematology and serum biochemistry in healthy dogs. Ten intact beagle dogs, 3 females, and 7 males, with a mean age of 3 years, and mean body mass of 14.3kg, body condition score between 4.0/9 and 4.5/9 were evaluated. The WBV sessions were done with the dog standing up on all 4 feet on a vibrating platform. Daily session of 30Hz for 5 minutes, followed by 50Hz for 5 minutes and finishing with 30Hz for 5 minutes was accomplished for 5 days. The velocity and amplitude of the vibrating platform were 12-40m/s2 and 1.7-2.5mm, respectively. Blood samples were collected, before and immediately after the WBV platform exercise session, and 1 and 6 hours after the end of each session for 5 days. In addition, blood samples were collected 24 hours and 48 hours after the last WBV platform exercise session. Complete blood count and serum biochemistry (alanine aminotransferase, aspartate aminotransferase, creatine kinase, blood urea nitrogen, creatinine, and serum total protein) were the data analyzed. The erythrocytes, hemoglobin, and packet cell volume values decreased, whereas the leukocytes, neutrophils, and eosinophils values increased after WBV platform exercise sessions; however, all values were within the reference range. Other hematological and serum biochemical parameters did not show important variations. In conclusion, the WBV exercise sessions attended for 5 consecutive days did not adversely affect the hematology and serum biochemistry of adult healthy dogs.

A 7-week-old, 1.045kg female beagle dog was referred to investigate a supposed vascular ring anomaly. Cone beam computed tomography with contrast enhanced arterial phase accomplished by a rapid manual intravenous injection of iodinated agent during the scanning process revealed a persistent right aortic arch and an aberrant left subclavian artery that compressed dorsally the esophagus in the cranial mediastinum. Third left intercostal thoracotomy was performed to transect the left subclavian artery. This is the first description of a vascular ring anomaly that was diagnosed with a cone beam computed tomography in veterinary medicine.

Objective To compare the effects of thiopentone, propofol and alfaxalone on arytenoid cartilage motion and establish the dose rates to achieve a consistent oral laryngoscopy examination. Study design Randomised crossover study. Animals Six healthy adult Beagle dogs. Methods Each dog was randomly administered three induction agents with a 1-week washout period between treatments. Thiopentone (7.5 mg kg −1 ), propofol (3 mg kg −1 ) or alfaxalone (1.5 mg kg −1 ) was administered over 1 minute for induction of anaesthesia. If the dog was deemed inadequately anaesthetised, then supplemental boluses of 1.8, 0.75 and 0.4 mg kg −1 were administered, respectively. Continual examination of the larynx, using a laryngoscope, commenced once an adequate anaesthetic depth was reached until examination end point. The number of arytenoid motions and vital breaths were counted during three time periods and compared over time and among treatments. Data were analysed using Friedman and Mann–Whitney U tests, Spearman rho and a linear mixed model with post hoc pairwise comparison with Tukey correction. Results The median (range) induction and examination times were 2.8 (2.0–3.0), 2.7 (2.0–3.3) and 2.5 (1.7–3.3) minutes ( p = 0.727); and 14.1 (8.0–41.8), 5.4 (3.3–14.8) and 8.5 (3.8–31.6) minutes ( p = 0.016) for thiopentone, propofol and alfaxalone, respectively. The median dose rates required to achieve an adequate anaesthetic depth were 6.3 (6.0–6.6), 2.4 (2.4–2.4) and 1.2 (1.2–1.2) mg kg −1 minute −1 , respectively. There was no significant difference for the total number of arytenoid motions ( p = 0.662) or vital breaths ( p = 0.789) among induction agents. Conclusion and clinical relevance The number of arytenoid motions were similar among the induction agents. However, at the dose rates used in this study, propofol provided adequate conditions for evaluation of the larynx with a shorter examination time which may be advantageous during laryngoscopy in dogs.

Dogs are highly sensitive to sound stimuli, especially fireworks, firearms, and thunder, and therefore these sounds are used as models of stress reactivity in dogs. Companion and laboratory dogs may respond differently to stressful stimuli, due to differences in management and their relationship with humans. Therefore, the reactivity of beagle dogs (laboratory) and companion dogs to an acute acoustic stress model was studied by analysing the heart rate variability (HRV; cardiac interval values), serum cortisol levels and various behavioural parameters. Eight beagles and six privately owned dogs with no history of phobia to thunder were used. The sound stimulus consisted of a standardized recording of thunder for 2.5 min with a maximum intensity of 103–104 dB. To evaluate the HRV, cardiac intervals were recorded using a frequency meter (Polar RS800CX model), and later the data were analysed using CardioSeries 2.4.1 software. In both laboratory and companion dogs, thunder promoted an increase in the power of the LF band of the cardiac interval spectrum, in the LF/HF ratio and in the HR, and a decrease in the power of the HF band of the cardiac interval spectrum. Companion dogs showed higher cortisol levels, than beagles, independently of the time point studied and a significant increase in the cortisol levels 15 min after acoustic stress, while beagles did not show any alterations in their cortisol levels in response to the sound. On the other hand, beagles showed higher scores in the trembling, hiding, vigilance, running, salivation, bolting and startle parameters than companion dogs. Our results showed that independently of the sound stimulus, companion dogs had higher cortisol levels than laboratory dogs. Furthermore, the sound stimulus induced a marked autonomic imbalance towards sympathetic predominance in both laboratory and companion dogs. However a significant increase in the cortisol was observed only in companion dogs. On the other hand, in general the behavioural response was more pronounced in laboratory dogs than in companion dogs.

The aim of the present study was to investigate virtual population pharmacokinetic using physiologically based pharmacokinetic (PBPK) model for evaluating bioequivalence of oral lacidipine formulations in dogs. The dissolution behaviors of three lacidipine formulations including one commercial product and two self-made amorphous solid dispersions (ASDs) capsules were determined in 0.07% Tween 80 media. A randomized 3-period crossover design in 6 healthy beagle dogs after oral administration of the three formulations at a single dose of 4 mg was conducted. The PBPK modeling was utilized for the virtual bioequivalence study. In vitro dissolution experiment showed that the dissolution behaviors of lacidipine amorphous solid dispersions (ASDs) capsules, which was respectively prepared by HPMC-E5 or Soluplus, as polymer displayed similar curves compared with the reference formulation in 0.07% Tween 80 media. In vivo pharmacokinetics experiments showed that three formulations had comparable maximum plasma drug concentration ( C max ), and the time ( T max ) to reach C max of lacidipine tablet, which was prepared by Soluplus, as polymer was slower than other two formulations in consistency with the in vitro dissolution rate. The 90% confidence interval (CI) for the C max , AUC 0–24 h and AUC 0–∞ of the ratio of the test drug to the referencedrug exceeded the acceptable bioequivalence (BE) limits (0.80–1.25). However, the 90% CI of the AUC 0–24 h , AUC 0–∞ and C max of the ratio of test to reference drug were within the BE limit, calculated using PBPK modeling when the virtual subjects reached 24 dogs. The results all demonstrated that virtual bioequivalence study can overcome the inequivalence caused by inter-subject variability of the 6 beagle dogs involved in in vivo experiments.

Objective Composite of synthetic octacalcium phosphate and collagen (OCP/Col) enhances bone regeneration if implanted into human, canine, or rodent bone defects. This study was designed to investigate the influence on eruption of the permanent successor tooth and alveolar height of OCP/Col implantation into extraction cavities of deciduous teeth. Design Disks of OCP/Col prepared from synthetic granules of octacalcium phosphate (OCP) and porcine atelocollagen, and commercially available sintered porous β-tricalcium phosphate (β-TCP) was implanted into the prepared defect of eleven male beagle dogs by extraction of two deciduous premolars. Untreated group had nothing implanted into the prepared defect, and physiological group (Physiol group) was observed without any treatment. Periodical macroscopic and radiographic examinations were performed until the period equivalent to the physiological eruption of permanent successor teeth (P3 and P4). Results Although no unerupted permanent successor teeth were observed among the OCP/Col, Untreated, and Physiol groups, two permanent successor teeth were unerupted in the β-TCP group. No significant difference of the alveolar heights or the eruptive position in P3 and P4 was observed between OCP/Col and Physiol groups. Conclusion OCP/Col implantation in the alveolar region that included the unerupted permanent successor teeth would cause no disturbance of permanent tooth eruption and preserve the alveolar ridge.