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.     

Effect of inclusion of sugar beet pulp,pelleting and season on laying hen performance

1. The effect of three metabolisable energy (ME) concentrations 12.2, 11.3 and 10.5 MJ ME/kg and two forms of diet (mash and pellet) on egg production in summer and winter were studied. The different ME values were obtained by diluting the 12.2 MJ ME/kg diet with sugar beet pulp of 2.88 MJ/kg DM. In a 3rd summer experiment the water intake of hens on these diets was examined. Data were analysed by factorial analysis of variance, and the relationship between performance and dietary energy concentration was examined by regression analysis.

2. The use of low energy diets (10.5 to 11.3 MJ ME/kg) decreased egg production in both seasons, but pelleting diets improved egg production and egg weight in summer. Egg weight was not affected by energy density in winter, but decreased in the summer when energy density increased.

3. In winter, food consumption was not affected by the dietary ME, while in summer food consumption increased when the dietary ME increased. Therefore, energy intake was not the same at all energy densities, but tended to increase as the energy density increased.

4. In summer, pelleting improved food efficiency and egg production and increased water consumption and the ratio of water to food intake. Water intake and water: food ratio decreased with increasing dietary energy concentration.     

Active bleb formation is abated in Lytechinus variegatus red spherule coelomocytes after disruption of acto‐myosin contractility

Red spherule coelomocytes are immune cells in the sea urchin Lytechinus variegatus that have been characterized as motile O₂ transport cells. Video microscopy of living red spherule coelomocytes reveals a constitutive, dynamic array of cellular morphologies and movements. Cells continuously send out and retract membrane blebs all over the cell surface as part of their normal cellular physiology. Disruption of microtubules by perfusion with either nocodazole or taxol had no effect on bleb formation or motility. Perfusion with cytochalasin B abated bleb formation and revealed cells that exhibited multiple small spheres attached by short membrane extensions. Attenuation of blebbing and intracellular organelle motility were restored by washing out with cytochalasin B. Treatment with phalloidin also abated bleb formation and revealed a smooth, spherical cellular morphology. The effects of phalloidin were completely reversible after washout. Red spherule coelomocytes treated with blebbistatin rounded up with an irreversible retraction of blebs into surface blebs that were greatly reduced in size, number and motility. Normal cell surface bleb formation and intracellular organelle motility were not restored after washout of the drug. These results indicate that the acto‐myosin contractile mechanism contributes to the dynamics of constitutive cell surface membrane blebbing in invertebrate immune cells.     

Planning for the future: identifying conservation priority areas for Iberian birds under climate change

Context

Species are expected to shift their distributions in response to global environmental changes and additional protected areas are needed to encompass the corresponding changes in the distributions of their habitats. Conservation policies are likely to become obsolete unless they integrate the potential impacts of climate and land-use change on biodiversity.

Objectives

We identify conservation priority areas for current and future projected distributions of Iberian bird species. We then investigate the extent to which global change informed priority areas are: (i) covered by existing protected area networks (national protected areas and Natura 2000); (ii) threatened by agricultural or urban land-use changes.

Methods

We use outputs of species distributions models fitted with climatic data as inputs in spatial prioritization tools to identify conservation priority areas for 168 bird species. We use projections of land-use change to then discriminate between threatened and non-threatened priority areas.

Results

19% of the priority areas for birds are covered by national protected areas and 23% are covered by Natura 2000 sites. The spatial mismatch between protected area networks and priority areas for birds is projected to increase with climate change. But there are opportunities to improve the protection of birds under climate change, as half of the priority areas are currently neither protected nor in conflict with urban or agricultural land-uses.

Conclusions

We identify critical areas for bird conservation both under current and climate change conditions, and propose that they could guide the establishment of new conservation areas across the Iberian Peninsula complementing existing protected areas.