Single and multiple dose pharmacokinetics of a novel mirtazapine transdermal ointment in cats

Single and multiple dose pharmacokinetics (PK) of mirtazapine transdermal ointment applied to the inner ear pinna of cats were assessed. Study 1 was a randomized, cross‐over single dose study (n = 8). Cats were treated once with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner ear pinna (treatment) or administered orally (control) and then crossed over after washout. Plasma was collected predose and at specified intervals over 96 hr following dosing. Study 2 was a multiple dose study (n = 8). Cats were treated daily for 14 days with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner pinna. Plasma was collected on Day 13 predose and at specified intervals over 96 hr following the final dose. In Study 1, single transdermal administration of mirtazapine resulted in mean T_max = 15.9 hr, C_max = 21.5 ng/mL, AUC_0‐24 = 100 ng*hr/mL, AUC_0‐∞ = 260 ng*hr/mL and calculated half‐life = 26.8 hr. Single oral administration of mirtazapine resulted in mean T_max = 1.1 hr, C_max = 83.1 ng/mL, AUC_0‐24 = 377 ng*hr/mL, AUC_0‐∞ = 434 ng*hr/mL and calculated half‐life = 10.1 hr. Mean relative bioavailability (F) of transdermal to oral dosing was 64.9%. In Study 2, daily application of mirtazapine for 14 days resulted in mean T_max = 2.1 hr, C_max = 39.6 ng/mL, AUC_0‐24 = 400 ng*hr/mL, AUC_0‐∞ = 647 ng*hr/mL and calculated half‐life = 20.7 hr. Single and repeat topical doses of a novel mirtazapine transdermal ointment achieve measurable plasma concentrations in cats.     

Meta‐analysis of the energy and protein requirements of hair sheep raised in the tropical region of Brazil

The objective of this study was to estimate, through mathematical models, energy and protein requirements for maintenance and gain of hair sheep raised in the tropical region of Brazil. To determine the equation parameters, a meta‐analysis of seven independent experiments of nutrient requirements was performed, comprising a total of 243 experimental units (animals), which were conducted under tropical conditions, using hair sheep in growing and finishing phases and endowed of the following quantitative data for each animal: body weight (BW ), empty body weight (EBW ), average daily gain (ADG ), empty body gain (EBG ), heat production (HP ), metabolizable energy intake (MEI ), retained energy (RE ), metabolizable protein intake (MPI ) and body protein content. The regression equations generated were as follows: for Net Energy for maintenance, (NE _m): ; for Net Energy for gain, (NE _g): ; for Metabolizable Protein for maintenance,(MP _m): MPI _(g/day) = 24.8470 (±7.3646) + 560.28 (±99.6582) × EBG _(kg/day); for Net Protein for gain, (NP _g): . The NE _m requirement was 0.246 MJ EBW^?0.75 day^?1. The metabolizable energy for maintenance requirement was 0.391 MJ EBW^?0.75 day^?1. Considering an ADG of 100 g, the NE _g requirement ranged from 0.496 to 1.701 MJ/day for animals with BW ranging from 10 to 40 kg respectively. The efficiencies of use of the metabolizable energy for maintenance and gain were 0.63 and 0.36 respectively. The MP _m requirement was 3.097 g EBW^?0.75 day^?1. Considering an ADG of 100 g, the NP _g requirement ranged from 12.4 to 10.5 g/day for animals with BW ranging from 10 to 40 kg respectively. The total metabolizable energy and protein requirements were lower than those reported by the NRC and AFRC systems. Thus, our results support the hypothesis that nutrient requirements of hair sheep raised in tropical regions differ from wool sheep raised in temperate regions. Therefore, the use of the equations designed in this study is recommended.     

Effect of sweet potato vines on performance parameters and some carcass characteristics of rabbits

Conventional feedstuffs in Brazil are expensive, which has led to the search for less conventional cheaper and locally available feedstuffs. Thus, this study was carried out to determine the dietary effect of dry sweet potato vines (SPV) on the performance and some carcass characteristics of rabbits. A total of twenty‐seven weaned White New Zealand rabbits (14 male and 13 female) 35 days old with an average initial weight of 755 g were allocated into three treatments. Nine rabbits were assigned to each treatment in a completely randomized design. Three diets were formulated to similar protein and energy levels: 0SPV – diet without inclusion of dry sweet potato vines; 10SPV – diet with 10% alfalfa hay replaced by dry sweet potato vines; and 15SPV – diet with 15% of alfalfa hay replaced by dry sweet potato vines. The experiment lasted for 49 days during which data for feed intake and body weight were recorded. The daily feed intake ranged from 73.17 to 78.02 g; daily weight gain from 22.32 to 23.17 g; feed conversion ratio (FCR) from 3.16 to 3.49 and final live weight ranged from 1839.44 to 1880.55 g. None of the evaluated performance parameters as well as carcass weight, heart weight and percentages of fat and protein in meat were significantly affected by any of the tested dietary treatments. However, the liver weight was statistically lower in animals fed the diets containing 10% of SPV, mainly due to lower glucose content. Glycogen within the tissue, did not differ significantly among treatments. It was therefore concluded that up to 15% of SPV can successfully be included in the diet of rabbits as a cheaper replacement for alfalfa hay without adversely affecting performance.     

Transgenerational epigenetic variance for body weight in meat quails

We aimed to estimate transgenerational epigenetic variance for body weight using genealogical and phenotypic information in meat quails. Animals were individually weighted from 1 week after hatching, with weight records at 7, 14, 21, 28, 35 and 42 days of age (BW7, BW14, BW21, BW28, BW35 and BW42, respectively). Single‐trait genetic analyses were performed using mixed models with random epigenetic effects. Variance components were estimated by the restricted maximum likelihood method. A grid search for values of autorecursive parameter (λ) ranging from 0 to 0.5 was used in the variance component estimation. This parameter is directly related to the reset coefficient (ν) and the epigenetic coefficient of transmissibility (1‐ν). The epigenetic effect was only significant for BW7. Direct heritability estimates for body weight ranged in magnitude (from 0.15 to 0.26), with the highest estimate for BW7. Epigenetic heritability was 0.10 for BW7, and close to zero for the other body weights. The inclusion of the epigenetic effect in the model helped to explain the residual and non‐Mendelian variability of initial body weight in meat quails.     

Melatonin reduces apoptotic cells,SOD2 and HSPB1 and improves the in vitro production and quality of bovine blastocysts

Effects of adding different concentrations of melatonin (10^?7, 10^?9 and 10^?11 M) to maturation (Experiment 1; Control, IVM  + 10^?7, IVM  + 10^?9, IVM  + 10^?11) and culture media (Experiment 2; Control, IVC  + 10^?7, IVC  + 10^?9, IVC  + 10^?11) were evaluated on in vitro bovine embryonic development. The optimal concentration of melatonin (10^?9 M) from Experiments 1–2 was tested in both maturation and/or culture media of Experiment 3 (Control, IVM  + 10^?9, IVC  + 10^?9, IVM /IVC  + 10^?9). In Experiment 1, maturated oocytes from Control and IVM  + 10^?9 treatments showed increased glutathione content, mitochondrial membrane potential and percentage of Grade I blastocysts (40.6% and 43%, respectively). In Experiment 2, an increase in the percentage of Grade I blastocysts was detected in IVC  + 10^?7 (43.5%; 56.7%) and IVC  + 10^?9 (47.4%; 57.4%). Moreover, a lower number and percentage of apoptotic cells in blastocysts were observed in the IVC  + 10^?9 group compared to Control (3.8 ± 0.6; 3.6% versus 6.1 ± 0.6; 5.3%). In Experiment 3, the IVC  + 10^?9 treatment increased percentage of Grade I blastocysts with a lower number of apoptotic cells compared to IVM /IVC  + 10^?9 group (52.6%; 3.0 ± 0.5 versus 46.0%; 5.4 ± 1.0). The IVC  + 10^?9 treatment also had a higher mRNA expression of antioxidant gene (SOD 2) compared to the Control, as well as the heat shock protein (HSPB 1) compared to the IVM  + 10^?9. Reactive oxygen species production was greater in the IVM /IVC  + 10^?9 treatment group. In conclusion, the 10^?9 M concentration of melatonin and the in vitro production phase in which it is used directly affected embryonic development and quality.     

Interactions between different media and follicle‐stimulating hormone supplementation on in vitro culture of preantral follicles enclosed in ovarian tissue derived from collared peccaries (Pecari tajacu Linneaus, 1758)

The aim was to verify the effect of follicle‐stimulating hormone (FSH) supplementation to α‐MEM+ or TCM199+ media on the in vitro development of ovarian preantral follicles (PFs) derived from collared peccaries. Ovaries (n = 5 pairs) were collected and divided into fragments destined to control group (non‐cultured) or treatments that were cultured for 7 days. The PFs morphology, growth and activation were evaluated by classical histology. The immunohistochemistry markers Ag‐NOR and PCNA were used for nuclear proliferation analysis, and the picrosirius red labelling was used for ovarian extracellular matrix (ECM) evaluation. After 7‐day culture, only the TCM199+ treatment maintained the proportion of intact PFs similar to day 1 (63.2%), but no differences were found among treatments (p > .05). In addition, a significant increase in the growing follicles proportion was verified for all the treatments, indicating follicular activation (p > .05). By the Ag‐NOR analysis, only the TCM199+/FSH maintained the nuclear proliferation similar to the first day (p > .05). The picrosirius red staining revealed that the ECM remained intact in all the treatments (p > .05). We suggest the use of TCM199+ medium supplemented of FSH for the in vitro development of peccaries PFs under 7‐day culturing conditions.     

ACE inhibition in goats under fixed‐time artificial insemination protocol increases the pregnancy rate and twin births

To assess the effect of the angiotensin‐converting enzyme (ACE) inhibition on the efficiency of the fixed‐time artificial insemination (TAI), 69 goats were divided randomly into two groups: enalapril (n = 35) and control (n = 34). In the experiment, all animals underwent the protocol of fixed‐time artificial insemination for 12 days. Enalapril group received enalapril maleate dissolved in saline (Enalapril, Lab Teuto Ltda) subcutaneously at the following doses: 0.2 mg/kg/day in D0‐D2; 0.3 mg/kg/day in D3‐D6 and 0.4 mg/kg/day in D7‐D11. The control group received the corresponding volume of 0.9% saline solution. We performed a single insemination 36 hr after sponge removal using frozen semen from two adult male goats with recognized fertility. The ultrasound pregnancy diagnosis was 30 days after the artificial insemination (AI). There was significant increase in pregnancy rates and twinning as well as a decrease in foetal loss in animals receiving enalapril (p < .01). The use of ACE inhibitors during the TAI protocol was shown to be a promising alternative to increase the efficiency of such reproductive biotechnology.