Morphological changes of physeal cartilage and secondary ossification centres in the developing femur of the house mouse (Mus musculus): A micro‐CT based study

In mammals, long bones are formed by ossification of a cartilaginous mould during early stages of development, through the formation of structures called the primary ossification centre, the secondary ossification centres (SOCs) and the physeal cartilages (PCs). The PC is responsible for long bone growth. The morphology of the PC and the SOCs varies during different stages of femoral growth. In this respect, several details involving the process of murine femoral development are lacking. In the present study, a morphological characterization of femur development from the embryonic period to adulthood in mice was studied using micro‐computed tomography (micro‐CT). To achieve this aim, femora were collected at embryonic day (E) 14.5, E16.5 and E18.5 and at postnatal day (P)1, P7, P14, P35, P46 and P52. CT images were obtained using a micro‐CT scanner (X‐SkyScan 1172; Micro Photonics) and analysed using the micro‐CT 3D visualization software Mimics (Materialise NV, Leuven, Belgium) and NRecon (Micro Photonics). The results of the present study revealed that the femur and its PCs and SOCs undergo morphological changes during different stages of development, including changes in their shape as well as position and thickness. These changes may be due to the response of the femur to mechanical loads imposed by muscle surrounding the bone during these stages of development. The result of the present study is important to improve our knowledge related to ossification and growth patterns of mouse femur during development.     

Abnormal Sysmex XT‐2000iV DIFF scattergram in a cat with a prominent mastocytemia

A 2‐year‐old neutered male domestic shorthair cat was presented to the emergency service of the National Veterinary School of Toulouse (France) for acute vomiting and diarrhea with lethargy, inappetence, and adypsia for the past 48 hours. Complete blood counts were performed with the ProCyte DX at the emergency department and with the Sysmex XT‐2000iV at the laboratory 2 weeks later. The scattergrams from the two analyzers revealed similar unusual and abnormal dot plots. The Sysmex XT‐2000iV DIFF scattergram also showed no clear separation between different leukocyte populations. The eosinophil cluster was in an abnormal location compared with that of the “typical” location in a normal cat. A blood smear evaluation revealed the presence of numerous mast cells. Thus, we hypothesized that the Sysmex XT‐2000iV had detected the mast cell population, and this led to errors in the differential counts. To explore this hypothesis, we manually gated on the DIFF scattergram and performed a manual differential on the blood smear. With this new gating strategy, the Sysmex XT‐2000iV and manual differentials were similar. Thus, in the case of systemic mastocytosis, mast cells can be located between the lymphocyte, monocyte, and eosinophil clusters on scattergrams.     

The α2A‐adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine

Xylazine, the classical α₂‐adrenoceptor (α₂‐AR) agonist, is still used as an analgesic and sedative in veterinary medicine, despite its low potency and affinity for α₂‐ARs. Previous pharmacological studies suggested that the α_2A‐AR subtype plays a role in mediating the clinical effects of xylazine; however, these studies were hampered by the poor subtype‐selectivity of the antagonists used and a lack of knowledge of their bioavailability in vivo. Here, we attempted to elucidate the role of the α_2A‐AR subtype in mediating the clinical effects of xylazine by comparing the analgesic and sedative effects of this drug in wild‐type mice with those in α_2A‐AR functional knockout mice using the hot‐plate and open field tests, respectively. Hippocampal noradrenaline turnover in both mice was also measured to evaluate the contribution of α_2A‐AR subtype to the inhibitory effect of xylazine on presynaptic noradrenaline release. In wild‐type mice, xylazine (10 or 30 mg/kg) increased the hot‐plate latency. Furthermore, xylazine (3 or 10 mg/kg) inhibited the open field locomotor activity and decreased hippocampal noradrenaline turnover. By contrast, all of these effects were abolished in α_2A‐AR functional knockout mice. These results indicate that the α_2A‐AR subtype is mainly responsible for the clinical effects of xylazine.     

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.     

Pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites in horses after intravenous administration of four doses

The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine‐3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine‐6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady‐state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min^?1 kg^?1, respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites.     

Pharmacokinetics of levosulpiride after single‐dose administration in goats (Capra hircus) by different routes of administration

Levosulpiride (LSP) is the l‐enantiomer of sulpiride, and LSP recently replacing sulpiride in several EU countries. Several studies about LSP in humans are present in the literature, but neither pharmacodynamic nor pharmacokinetic data of LSP is present for veterinary species. The aim of this study was to assess the pharmacokinetic profile of LSP after intravenous (IV), intramuscular (IM), and oral (PO) administration in goats. Animals (n = 6) were treated with 50 mg LSP by IV, IM, and PO routes according to a randomized cross‐over design (3 × 3 Latin‐square). Blood samples were collected prior and up to 24 hr after LSP administration and quantified using a validated HPLC method with fluorescence detection. IV and IM administration gave similar concentration versus time curve profiles. The IM mean bioavailability was 66.97%. After PO administration, the drug plasma concentrations were detectable only in the time range 1.5–4 hr, and the bioavailability (4.73%) was low. When the AUC was related to the administered dose in mg/kg, there was a good correlation in the IV and IM groups, but very low correlation for the PO route. In conclusion, the IM and IV administrations result in very similar plasma concentrations. Oral dosing of LSP in goats is probably not viable as its oral bioavailability was very low.     

Performance,breast meat yield and abdominal fat deposition of male broiler chickens fed diets supplemented with DL‐xnethionine or DL‐xnethionine hydroxy analogue free acid

1. An experiment was conducted to compare the relative bioefficacy of DL‐methionine hydroxy analogue free acid (DL‐MHA‐FA) with DL‐methionine in broiler chickens. Responses used for comparison were weight gain and food efficiency between 7 and 35 d of age, and breast meat deposition, food cost per kg of breast meat, and abdominal fat at 41 d of age.

2. A total of 2160 seven‐day‐old male broiler chicks were used. The feeding programme consisted of a starter diet from 7 to 21 d, and a finisher diet till the end of the experiment. The starter basal diet contained 6.1 g/kg total sulphur‐containing amino acids (TSAA), and an estimated metabolisable energy (ME) content of 13.2 MJ/kg. The finisher diet contained 5.8 g/kg TSAA and an estimated ME content of 13.6 MJ/kg. Four concentrations of DL‐methionine and DL‐MHA‐FA were added at 0.5g/kg increments on an equimolar basis. Therefore, there were 9 experimental treatments which were each applied to 6 replicates of 40 chicks. Weight gain and food efficiency were determined at 35 d of age. Breast yield and carcase fat were measured at 41 d.

3. Significant responses to graded amounts of both methionine sources were observed in weight gain, food efficiency, breast meat percentage, and food cost per kg of breast meat. The responses fitted exponential regression curves. Based on the regression coefficients, equimolar bioefficacy of DL‐MHA‐FA relative to DL‐methionine was 80% for daily gain, 83% for food efficiency, 51% for breast meat yield, and 66% for food cost per kg of breast meat. Differences between the 2 sources were significant (P< 0.05) for breast meat yield and food cost per kg of meat and (P< 0.10) for food efficiency.