Effect of Chronic Administration of Phenobarbital,or Bromide,on Pharmacokinetics of Levetiracetam in Dogs with Epilepsy

Background

Levetiracetam (LEV) is a common add‐on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs.

Hypothesis/Objectives

To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs.

Animals

Eighteen client‐owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB–BR group, n = 6).

Methods

Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area‐under‐the‐curve (AUC) calculated to the last measured time point.

Results

Compared to the PB and PB–BR groups, the BR group had significantly higher peak concentration (C _max) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028).

Conclusions and Clinical Importance

Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add‐on treatment with phenobarbital in dogs.     

Pharmacokinetics of cefquinome in tilapia (Oreochromis niloticus) after a single intramuscular or intraperitoneal administration

The pharmacokinetics of cefquinome was studied in plasma after a single dose (10 mg/kg) of intramuscular (i.m.) or intraperitoneal (i.p.) administration to tilapia (Oreochromis niloticus) in freshwater at 30 °C. Ten fish per sampling point were examined after treatment. The data were fitted to two‐compartment open models following both routes of administration. The estimates of total body clearance (CL/F), volume of distribution (Vd/F), and absorption half‐life (T_1/2ka) were 0.049 and 0.037 L/h/kg, 0.41 and 0.33 L/kg, and 0.028 and 0.035 h following i.m. and i.p. administration, respectively. After i.m. injection, the elimination half‐life (T_1?2β) was calculated to be 5.81 h, the maximum plasma concentration (C_max) to be 49.40 μg/mL, the time to peak plasma cefquinome concentration (T_max) to be 0.14 h, and the area under the plasma concentration–time curve (AUC) to be 204.6 μg h/mL. Following i.p. administration, the corresponding estimates were 6.05 h, 44.39 μg/mL, 0.17 h and 267.8 μg h/mL. The minimum inhibitory concentrations of cefquinome, determined for 30 strains of Streptococcus agalactiae isolated from diseased tilapia, ranged from 0.015 to 0.12 μg/mL. Results from these studies support that 10 mg cefquinome/kg body weight daily could be expected to control tilapia bacterial pathogens inhibited in vitro by a minimal inhibitory concentration value of ≤2 μg/mL.     

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.     

Thoracoscopic Lung Lobectomy for Primary Lung Tumors in 13 Dogs

Objectives

To report our experience with thoracoscopic lung lobectomy in dogs with primary lung tumors and compare the long‐term outcome between dogs with primary lung tumors treated with lobectomy via thoracoscopy or thoracotomy.

Study Design

Retrospective case series; case–control study.

Animals

Thirteen dogs with primary lung tumors treated with thoracoscopic lung lobectomy; case‐matched cohort of 9 dogs with primary lung tumors treated with lobectomy via thoracotomy.

Methods

Medical records from dogs that underwent thoracoscopic lung lobectomy at a single institution were reviewed. Only cases with primary lung tumors were included. Surgical complications and conversion rate were reported. Cases without conversion and with clean margins on histologic examination were matched on prognostic criteria to cases with primary lung tumors treated with lobectomy via thoracotomy. Survival was compared between thoracoscopy and thoracotomy.

Results

Thirteen dogs with primary lung tumors that measured 2.2–7 cm underwent thoracoscopic lung lobectomy. Nine dogs were diagnosed with carcinoma and 4 with histiocytic sarcoma. There were 3 conversions to open thoracotomy because of poor visualization. There were no differences in short‐term outcome between dogs that had their procedures completed via thoracoscopy and those that were converted to thoracotomy. Nine dogs with clean margins were matched with 9 dogs treated via thoracotomy. Mean (standard deviation) followup was 367 (327) days for dogs undergoing thoracoscopy and 603 (612) days for dogs undergoing thoracotomy. The 2‐year survival rate was 44% for thoracoscopy and 56% for thoracotomy (P = .942).

Conclusion

Selected primary lung tumors in dogs can be safely resected with thoracoscopy and not affect long‐term outcome.

     

Distribution and Diversity of Salmonella Strains in Shipments of Hatchling Poultry,United States, 2013

Multistate outbreaks of salmonellosis associated with live poultry contact have been occurring with increasing frequency. In 2013, multistate outbreaks of salmonellosis were traced back to exposure to live poultry, some of which were purchased at a national chain of farm stores (Farm store chain Y). This study was conducted at 36 stores of Farm store chain Y and was concurrent with the timing of exposure for the human outbreaks of salmonellosis in 2013. We used environmental swabs of arriving shipment boxes of hatchling poultry and shipment tracking information to examine the distribution, diversity and anti‐microbial resistance of non‐typhoidal Salmonella (NTS) across farm stores and hatcheries. Isolates recovered from shipment boxes underwent serotyping, anti‐microbial resistance (AMR) testing and pulsed‐field gel electrophoresis (PFGE). Postal service tracking codes from the shipment boxes were used to determine the hatchery of origin. The PFGE patterns were compared with the PFGE patterns of NTS causing outbreaks of salmonellosis in 2013. A total of 219 hatchling boxes from 36 stores in 13 states were swabbed between 15 March 2013 and 18 April 2013. NTS were recovered from 59 (27%) of 219 hatchling boxes. Recovery was not significantly associated with species of hatchlings, number of birds in the shipment box, or the presence of dead, injured or sick birds. Four of the 23 PFGE patterns and 23 of 50 isolates were indistinguishable from strains causing human outbreaks in 2013. For serotypes associated with human illnesses, PFGE patterns most frequently recovered from shipment boxes were also more frequent causes of human illness. Boxes positive for the same PFGE pattern most frequently originated from the same mail‐order hatchery. Only one of 59 isolates was resistant to anti‐microbials used to treat Salmonella infections in people. This study provides critical information to address recurrent human outbreaks of salmonellosis associated with mail‐order hatchling poultry.     

Dietary inclusion of dehydrated bocaiuva pulp increases the antioxidant potential of quail eggs

The aim of this study was to evaluate dietary supplementation of different levels of dehydrated bocaiuva pulp (DBP) on the productive performance of laying quails, and on lipid oxidation, and quality in their eggs. A total of 120 quails were distributed in a completely randomized design with six treatments (0%, 0.1%, 0.2%, 0.3%, 0.4% and 0.5% of DBP), five replicates and four birds per experimental unit. To evaluate lipid oxidation, the eggs were collected on five consecutive days at the end of the trial and distributed in a completely randomized experimental design in a 6 × 5 factorial scheme (eggs from quails fed different levels of DBP × evaluated fresh and after 7, 14, 21 and 28 days). The antioxidant potential of diets was improved (p < 0.05) when the DBP was added estimated as 2,2'‐azinobis‐3‐ethylbenzothiazolin‐6‐sulfonic acid (ABTS) free radical scavenging capacity. No effect (p > 0.05) was observed on feed intake, hen‐day egg production and feed conversion (kg/kg and kg/dz). There were no changes (p > 0.05) in the egg weight, Haugh unit, yolk index or eggshell percentage. Although no difference was observed (p > 0.05), when comparing each level with the control, a negative linear effect (p < 0.05) on specific gravity was observed. In addition, only the treatment with 0.5% pulp exhibited lower (p < 0.05) eggshell thickness compared with the control (0%). Thiobarbituric acid reactive substances (TBARS) analysis showed that as the dietary pulp level was increased, malondialdehyde content decreased linearly (p < 0.05) in the egg yolks, regardless of the storage period. Inclusion of DBP in the diets had no effect (p > 0.05) on the concentration of conjugated dienes in the eggs. The diets containing DBP showed a potential antioxidant effect, reducing the degree of lipid oxidation in egg yolk. However, no beneficial effects were observed on performance and egg quality.