Pharmacokinetics,tissue residues,and ex vivo pharmacodynamics of tylosin against Mycoplasma anatis in ducks

The pharmacokinetics of tylosin were investigated in 3 groups of ducks (n = 6). They received a single dose of tylosin (50 mg/kg) by intravenous (IV), intramuscular (IM), and oral administrations, respectively. Plasma samples were collected at various time points to 24 hr post-administration to evaluate tylosin concentration over time. Additionally, tylosin residues in tissues and its withdrawal time were assessed using 30 ducks which received tylosin orally (50 mg/kg) once daily for 5 consecutive days. After IV administration, the volume of distribution, elimination half-life, area under the plasma concentration–time curve, and the total body clearance were 7.07 ± 1.98 L/kg, 2.04 hr, 19.47 µg hr/ml, and 2.82 L hr⁻¹ kg⁻¹, respectively. After IM and oral administrations, the maximum plasma concentrations were 3.70 and 2.75 µg/ml achieved at 1 and 2 hr, and the bioavailability was 93.95% and 75.77%, respectively. The calculated withdrawal periods of tylosin were 13, 8, and 5 days for kidney, liver, and muscle, respectively. For the pharmacodynamic profile, the minimum inhibitory concentration for tylosin against M. anatis strain 1,340 was 1 µg/ml. The calculated optimal oral dose of tylosin against M. anatis in ducks based on the ex vivo pharmacokinetic/pharmacodynamic modeling was 61 mg kg⁻¹ day⁻¹.     

Nasopharyngeal tooth foreign body in a dog

An 8-year-old Shih-tzu dog was presented with a 2-week history of cough and nasal discharge. Upon presentation, the dog had constant open-mouth breathing with stertor and blood-tinged mucopurulent nasal discharge. Oral examination revealed a missing right mandibular second premolar tooth and severe periodontal disease. Computed tomography showed a radiodense, retropharyngeal foreign body. The foreign body was removed using caudal rhinoscopy. The foreign body was the right mandibular second premolar covered by thick calculus.     

Effects of Hormonal Supplementation on Nuclear Maturation and Cortical Granules Distribution of Canine Oocytes During Various Reproductive Stages

The aim of this study was to evaluate the effects of hCG, progesterone and oestradiol supplementation on nuclear and cytoplasmic maturation of canine oocytes cultured for 24, 48, 72 and 96 h. Oocytes obtained from 18 healthy bitches were divided into three groups according to their reproductive status (follicular, luteal and anoestrus stages) and cultured in TCM 199 + 25 UI/ml of hCG + 1 μg/ml of progesterone + 1 μg/ml of 17‐β oestradiol or without hormonal supplementation (control) for different periods. Then, they were stained with FITC‐LCA‐Hoescht for chromatin configuration and cortical granules distribution and evaluated under an epifluorescence microscope. Culture time and the influence of different stages of the oestrous cycle were also evaluated. The present study demonstrated that there was no significant difference among the reproductive stages. With regards to culture medium, only oocytes from the supplemented medium were able to complete meiosis; however, significant difference was only noticed in the percentage of MI stage oocytes (p < 0.05) in the follicular and luteal group at 72 h of culture. Most oocytes in germinal vesicle, germinal vesicle breakdown and metaphase I stage had cortical granules distributed throughout the cytoplasm (immature pattern), irrespective of the culture period (p < 0.05). Cortical granules distributed immediately beneath the plasma membrane (mature) was only observed in metaphase II stage oocytes, but not all of them presented matured cytoplasm. Our results reveal that cortical granules distribution in canine oocytes matured in vitro did not progressed in correspondence with nuclear stage changes and are in accordance with those from other species.     

High-resolution fluorodeoxyglucose positron emission tomography and magnetic resonance imaging findings of a pituitary microtumor in a dog

A 16-year-old, castrated, male English cocker spaniel dog was presented due to generalized alopecia. Routine clinical pathology, endocrine and abdominal ultrasonography results were consistent with a diagnosis of pituitary-dependent hyperadrenocorticism. The adenohypophyseal lesion was clearly visualized on both 3 T and 7 T magnetic resonance imaging (MRI) of the pituitary gland. Although biochemical and MRI findings were consistent with a functional pituitary microtumor, a pituitary lesion was not detected using ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET). This report firstly describes the application of high-resolution FDG-PET to a spontaneous pituitary microtumor in a dog.     

Ultra‐frequent HRAS p.Q61R somatic mutation in canine acanthomatous ameloblastoma reveals pathogenic similarities with human ameloblastoma

Ameloblastoma is a locally aggressive odontogenic tumour that occurs in humans and dogs. Most ameloblastomas (AM) in humans harbour mutually‐exclusive driving mutations in BRAF, HRAS, KRAS, NRAS or FGFR2 that activate MAPK signalling, and in SMO that activates Hedgehog signalling. The remarkable clinical and histological similarities between canine acanthomatous ameloblastoma (CAA) and AM suggest they may harbour similar driving mutations. In this study, aimed at characterizing the mutational status of SMO, BRAF, HRAS, KRAS, NRAS and FGFR2 in CAA, we used RNA sequencing, Sanger sequencing and restriction fragment length polymorphism assays to demonstrate that 94% of CAA (n = 16) harbour a somatic HRAS p.Q61R mutation. The similarities in MAPK‐activating mutational profiles between CAA and AM implicate conserved molecular mechanisms of tumorigenesis, thus, qualifying the dog as a potentially useful model of disease. Given the relevance of RAS mutations in the pathogenesis of odontogenic tumours and other types of cancer, the results of this study are of comparative, translational, and veterinary value.     

Pharmacokinetics of sanguinarine,chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half‐life (t_1/2) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (C_max) of DHSA (2.49 ± 1.4 μg/L) was higher that of SA (1.89 ± 0.8 μg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h^?1·kg^?1) with a t_1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.