Single‐ and multiple dose pharmacokinetics and multiple dose pharmacodynamics of oral ABT‐116 (a TRPV1 antagonist) in dogs

Six dogs were used to determine single and multiple oral dose pharmacokinetics of ABT‐116. Blood was collected for subsequent analysis prior to and at 15, 30 min and 1, 2, 4, 6, 12, 18, and 24 h after administration of a single 30 mg/kg dose of ABT‐116. Results showed a half‐life of 6.9 h, k_el of 0.1/h, AUC of 56.5 μg·h/mL, T_max of 3.7 h, and C_max of 3.8 μg/mL. Based on data from this initial phase, a dose of 10 mg/kg of ABT‐116 (no placebo control) was selected and administered to the same six dogs once daily for five consecutive days. Behavioral observations, heart rate, respiratory rate, temperature, thermal and mechanical (proximal and distal limb) nociceptive thresholds, and blood collection were performed prior to and 4, 8, and 16 h after drug administration each day. The majority of plasma concentrations were above the efficacious concentration (0.23 μg/mL previously determined for rodents) for analgesia during the 24‐h sampling period. Thermal and distal limb mechanical thresholds were increased at 4 and 8 h, and at 4, 8, and 16 h respectively, postdosing. Body temperature increased on the first day of dosing. Results suggest adequate exposure and antinociceptive effects of 10 mg/kg ABT‐116 following oral delivery in dogs.     

Enantioselective pharmacokinetics of ketoprofen in calves after intramuscular administration of a racemic mixture

The pharmacokinetic properties of ketoprofen were determined in 4‐week‐old calves after intramuscular (i.m.) injection of a racemic mixture at a dose of 3 mg/kg body weight. Due to possible enantioselective disposition kinetics and chiral inversion, the plasma concentrations of the R(?) and S(+) enantiomer were quantified separately, using a stereospecific HPLC‐UV assay. A distinct predominance of the S(+) enantiomer was observed, as well as significantly different pharmacokinetic parameters between R(?) and S(+) ketoprofen. More in specific, a greater value for the mean area under the plasma concentration–time curve (AUC_0→∞) (46.92 ± 7.75 and 11.13 ± 2.18 μg·h/mL for the S(+) and R(?) enantiomer, respectively), a lower apparent clearance (Cl/F) (32.8 ± 5.7 and 139.0 ± 25.1 mL/h·kg for the S(+) and R(?) enantiomer, respectively) and a lower apparent volume of distribution (V_d/F) (139 ± 14.7 and 496 ± 139.4 mL/kg for the S(+) and R(?) enantiomer, respectively) were calculated for the S(+) enantiomer, indicating enantioselective pharmacokinetics for ketoprofen in calves following i.m. administration.     

Expression of Mitochondria‐Associated Genes (PPARGC1A,NRF‐1, BCL‐2 and BAX) in Follicular Development and Atresia of Goat Ovaries

Most follicles undergo atresia during the developmental process. Follicular atresia is predominantly regulated by apoptosis of granulosa cells, but the mechanism underlying apoptosis via the mitochondria‐dependent apoptotic pathway is unclear. We aimed to investigate whether the mitochondria‐associated genes peroxisome proliferator‐activated receptor‐gamma, coactivator1‐alpha (PPARGC1A), nuclear respiratory factor‐1 (NRF‐1), B‐cell CLL/lymphoma 2 (BCL‐2) and BCL2‐associated X protein (BAX) played a role in follicular atresia through this pathway. The four mitochondria‐associated proteins (PGC‐1α, which are encoded by the PPARGC1A gene, NRF‐1, BCL‐2 and BAX) mainly expressed in granulosa cells. The mRNA and protein levels of PPARGC1A/PGC‐1α and NRF‐1 in granulosa cells increased with the follicular development. These results showed that these genes may play a role in the regulation of the follicular development. In addition, compared with healthy follicles, the granulosa cell in atretic follicles had a reduced expression of NRF‐1, increased BAX expression and increased ratio of BAX to BCL‐2 expression. These results suggested that changes of the mitochondria‐associated gene expression patterns in granulosa cells may lead to follicular atresia during goat follicle development.     

Flow cytometric evaluation of ki67 for the determination of malignancy grade in canine lymphoma

Ki67 is a nuclear antigen significantly correlated with degree of malignancy in human non‐Hodgkin lymphomas. We wanted to assess the ability of flow cytometric evaluation of Ki67 index (Ki67I) in differentiating the grade of malignancy in canine lymphomas. Ki67I was determined on lymph node aspirates of 90 immunophenotyped lymphomas classified according to the updated Kiel classification: 80 high grade (HG, 62 B cell and 18 T cell) and 10 low grade (LG, 3 B cell and 7 T cell) lymphomas. HG lymphomas showed significantly higher Ki67I compared with LG lymphomas (P < 0.0001). A significant difference in HG lymphomas was detected between B‐ and T‐immunophenotypes. Receiver operating characteristic (ROC) curve highlighted a high accuracy of Ki67I in recognizing HG lymphomas [area under the curve (AUC) = 99.4] and a cut‐off value of 12.2% was established (sensitivity = 96.3% and specificity = 100%). Thus, we suggest the combination of Ki67I flow cytometric determination and immunophenotype as a reliable tool to classify canine lymphomas.     

Evaluation of the carryover effect of antibiotic,bee pollen and propolis on growth performance,carcass traits and splenic and hepatic histology of growing rabbits

Sixty‐four nulliparous female rabbits were distributed among eight groups (eight animals/group). Group one was the unsupplemented control group; the other seven groups were supplemented with zinc bacitracin (ZnB) at 100 mg, or bee pollen (BP) and/or propolis (Pro) at 150 and 300 mg in a capsulated form, three times a week, day after day, continuously all over the experimental period. The experiment was run for eight parties; at each parity, 28 kids of each doe group (a total of 224 rabbits) were divided into two subgroups weaned, respectively, at 24 and 30 days of age. Thus, for each parity, there were 16 groups (eight does treatments × two weaning age, 14 rabbits per group). The growing rabbits fed the standard diets without supplements. The growth performance, the carcass traits, the liver and the spleen histology of rabbits were checked up to 90 days of age to find possible carryover effects of the supplements. The supplements had no significant effect on most of the growth performance at 90 days of age, but BP150 and BP+Pro300 increased the growth rate in comparison with ZnB group. The liver weight in the control, BP300 and Pro300 groups was higher than the ZnB one. The spleen weight was higher in the groups ZnB, BP150, Pro300 and BP+Pro300, followed by the control, BP300 and BP+Pro150 and thus Pro150. The heart % in the BP150 and Pro300 groups was higher than ZnB and BP+Pro150 groups. A lymphoid hyperplasia of splenic white pulp was observed in the BP+Pro groups, while propolis alone showed a mild activation of lymphobiosis. The Pro and BP groups showed the same picture of the control group exhibiting a hydropic degeneration of mostly hepatic cells, while the ZnB group exhibited adverse effect on the bile ducts featuring portal periductal inflammatory cells infiltration with epithelial hyperplasia reflecting chronic cholangitis.     

Clostridioides difficile on Ohio swine farms (2015): A comparison of swine and human environments and assessment of on‐farm risk factors

Swine are known reservoirs for Clostridioides difficile, formerly known as Clostridium difficile, and transmission from swine to human farm workers is strongly suggested by previous studies. This cross‐sectional study evaluated the potential role of farm environmental surfaces, including those in worker breakrooms and swine housing areas, in the possible transmission of C. difficile from swine to farm workers. Environmental surfaces and piglet faeces at 13 Ohio swine farms were sampled in 2015. Typical culturing techniques were performed to isolate C. difficile from samples, and amplification of toxin genes (tcdA, tcdB and cdtB) and PCR‐ribotyping were used to genetically characterize recovered isolates. In addition, sequencing of toxin regulatory gene, tcdC, was done to identify the length of identified deletions in some isolates. A survey collected farm‐level management risk factor information. Clostridioides difficile was recovered from all farms, with 42% (188/445) of samples testing positive for C. difficile. Samples collected from all on‐farm locations recovered C. difficile, including farrowing rooms (60%, 107/178), breakrooms (50%, 69/138) and nursery rooms (9%, 12/129). Three ribotypes recovered from both swine and human environments (078, 412 and 005) have been previously implicated in human disease. Samples taken from farrowing rooms and breakrooms were found to have greater odds of C. difficile recovery than those taken from nursery rooms (OR = 40.5, OR = 35.6, p < .001 respectively). Farms that weaned ≥23,500 pigs per year had lower odds of C. difficile recovery as compared to farms that weaned fewer pigs (OR = 0.4, p = .01) and weekly or more frequent cleaning of breakroom counters was associated with higher odds of C. difficile recovery (OR = 11.7, p < .001). This study provides important insights into the presence and characterization of C. difficile found in human environments on swine farms and highlights how these areas may be involved in transmission of C. difficile to swine farm workers and throughout the facility.