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.     

CD117‐ and vimentin‐positive telocytes in the bovine teat sphincter

Mastitis is a common economically relevant problem in dairy farming. As the major entry for pathogens is the papillary duct, one of the first defence mechanisms is the teat sphincter. This sphincter shows a rhythmic contractility of yet unknown origin. Searching for possible modulatory pacemaker cells, teat sphincters of eight cows were stained immunohistochemically with antibodies against CD117 and vimentin and evaluated microscopically for the presence of telocytes. CD117‐ and vimentin‐positive telocytes with telopodes were found in close contact with smooth muscle cells. Our findings present a first evidence of telocytes in the teat of bovines.     

Macro‐anatomical and morphometric studies of the hindlimb of grasscutter (Thryonomys swinderianus,Temminck‐1827)

The hindlimb of the grasscutter (Thryonomys swinderianus, Temminck‐1827) was studied using 12 adult (≥6 months) rats of either sex with the mean weights of 1.42 ± 0.20 kg and 0.82 ± 0.13 kg for buck (n = 6) and doe (n = 6), respectively (p < .05). Characteristics of the bones were studied by gross observation after their preparation. Measurements of different segments of the hindlimb were also taken, giving a total average length of 31.80 cm. Correlation coefficients between length of bone and weight of rats were positive (p < .05) in bucks for all bone segments, except the pes (p > .05), whereas those in does were all non‐significant (p > .05), with significant sexual dimorphism in the relationships. The average total number of bones in the hindlimb was 92, with no apparent sexual dimorphism. The bones of the hindlimb revealed important differences and similarities in morphology with those of other rodents. The Os coxae presented a relatively large obturator foramen, formed by the ramus of the ischium and shaft of the pubis. The femur had a body and two extremities with a prominent head, well‐defined neck and trochanter. The fibula, a slender bone with triangular‐shaped proximal extremity, ran down the length of tibia with proximal attachment (via cartilage) and distal fusion, leaving an extensive interosseus space. The pes revealed eight tarsals and four metatarsals; each of the metatarsals showed three phalanges.     

Categorization of the pelvic limb standing posture in nine breeds of dogs

The objective of the study was to categorize objectively nine breeds of healthy dogs according to pelvic limb standing posture. A total of 135 dogs from different breeds were used and the standing angles of the hip, stifle, and tarsal joints, together with the percentages of the greater trochanter, patella and tuber calcanei heights, with respect to crista iliaca height, were used as discriminant variables for the categorization of pelvic limb posture. All included breeds were allocated to three groups of the standing pelvic limb posture. The best discriminant variables between the three groups were the percentage of patellar height, and the standing angles of the stifle and tarsal joints. German shepherds, Anatolian shepherds, golden retrievers, Rottweilers, Belgian Malinois and Dobermann pinschers were well separated between 89% and 100% success rate for the categorization. The minimal success rate was determined in Berner sennenhunds as the ratio of 75%. It was also determined that Dobermann pinschers had the straightest pelvic limbs, while German shepherds had the most angulated pelvic limbs. Further studies are required to document the impact of postural differences in active and passive structure diseases of the locomotor system of the pelvic limb among dog breeds.     

Evaluation of three popular diets fed to pet sugar gliders (Petaurus breviceps): Intake,digestion and nutrient balance

Three diets fed to 12 pair‐housed sugar gliders, Petaurus breviceps, were evaluated through 5‐day intake and digestion trials following 10‐day transitions. Diets 1 and 2 comprised liquid formula mixes with added vegetables and fruit, and Diet 3 comprised extruded pellets and a liquid formula. Diets eaten contained 16 —19% crude protein, 3%–15% crude fat, 10%–11% neutral detergent fibre, 4%–20% starch and 8%–49% sugar (dry basis). Calculated individual dry matter intakes (DMI) ranged from 3.9 to 5.1 g/day, representing 58.2–78.4 kJ/day. DMI was greater for Diet 2 (7.2% BW) vs. Diet 1 (5.6; p = .006) and Diet 3 (4.2% BW; p = .003). Although these differences were no longer detectable on a MBW basis, animals were shown to have gained BW (+14.2 g; p = .03) on Diet 2. In addition to nutrient composition differing widely among diets, DM digestibility (DMD) was higher in Diet 1 (91.2%) compared to Diet 2 (87.3%; p = .03), but DMD for Diet 3 (88.9%) did not differ from other diets. Gliders demonstrated ability to digest a variety of energy substrates, including simple sugars (96%–99%), fats (81%–96%) and starches (79%–98%), as well as substantial insoluble dietary fibre (58%–75%), with significant difference among diets demonstrated for some nutrients. Animals displayed selective feeding behaviours, rejecting insoluble fibre in produce and preferring the lipid‐coated exterior of pellets. The diets used appeared to be balanced with respect to energy, protein and macromineral content, but may predispose to iron excess, other mineral imbalances (especially Ca deficiency) and obesity—clinical health issues described for pet gliders. Future focus on concentrations, types and utilization of dietary fibre in natural and captive diets, vitamin D metabolism and trace mineral interactions in sugar gliders would assist diet optimization for this highly gummivorous species.     

The effect of maternal obesity on fatty acid transporter expression and lipid metabolism in the full‐term placenta of lean breed swine

This study was conducted to evaluate the influence of back‐fat thickness (BF), at mating of sows, on the maternal and newborn circulating lipids, expression of placental fatty acids (FA) transporters and lipid accumulation in placenta. Full‐term placentas were obtained by vaginal delivery from BFI (9–14 mm; n = 37), BFII (15–19 mm; n = 43) and BFIII (20–27 mm; n = 38) sows according to BF at mating, and frozen placental sections were analysed for fat accumulation. Blood samples were collected from the sows of day 105 pregnancy and from cord blood at delivery. mRNA and protein expression levels were evaluated with real‐time RT‐PCR and Western blotting. Our results demonstrated that BFII females had significantly increased litter weight and placental efficiency, decreased maternal triglyceride (TG) and non‐esterified fatty acids (NEFA) levels, decreased maternal IL‐6, TNFα and leptin levels compared to BFIII females (p < .05). BFIII sows were associated with significantly decreased newborn TG levels, increased newborn glucose, IL‐6 and TNFα levels compared to BFI or BFII sows (p < .05). BFI and BFII females had significantly decreased placental TG, NEFA and cholesterol (CHOL) contents compared to BFIII females (p < .05). Moreover, decreased CD36, FATP1, FABP4, and FABP1 mRNA and protein and FATP4 protein expression, and increased LPL activity were also observed in BFIII group compared with BFII group (p < .05). PPARγ mRNA and protein and lipogenic genes such as SREBP‐1c, ACSL1, ACCα, FAS and SCD mRNA expression were downregulated or upregulated, respectively, in the placentas of BFIII sows compared to BFI or BFII sows (p < .05). Overall, this study demonstrated that there is no advantage, in terms of litter live size, litter weight and placental FA transport and metabolism, in performing the mating of sows with BF>19 mm.