Assessment of the long‐acting ivermectin formulation in sheep: Further insight into potential pharmacokinetic interactions

The aim of the current study was to evaluate the in vivo pharmacokinetic of ivermectin (IVM) after the administration of a long‐acting (LA) formulation to sheep and its impact on potential drug‐drug interactions. The work included the evaluation of the comparative plasma profiles of IVM administered at a single therapeutic dose (200 μg/kg) and as LA formulation at 630 μg/kg. Additionally, IVM was measured in different gastrointestinal tissues at 15 days posttreatment with both IVM formulations. The impact of the long‐lasting and enhanced IVM exposure on the disposition kinetics of abamectin (ABM) was also assessed. Plasma (IVM and ABM) and gastrointestinal (IVM) concentrations were analyzed by HPLC with fluorescent detection. In plasma, the calculated C_max and AUC_0‐t values of the IVM‐LA formulation were 1.47‐ and 3.35‐fold higher compared with IVM 1% formulation, respectively. The T_1/2ab and T_max collected after administration of the LA formulation were 2‐ and 3.5‐fold longer than those observed after administration of IVM 1% formulation, respectively. Significantly higher IVM concentrations were measured in the intestine mucosal tissues and luminal contents with the LA formulation, and in the liver, the increase was 7‐fold higher than conventional formulation. There was no drug interaction between IVM and ABM after the single administration of ABM at 15 days post‐administration of the IVM LA formulation. The characterization of the kinetic behavior of the LA formulation to sheep and its potential influence on drug‐drug interactions is a further contribution to the field.     

Experimental transmission of Hepatozoon americanum to rodents

Laboratory-raised cotton rats (Sigmodon hispidus), outbred white mice (Mus musculus), and C57BL/6J-Lystbg-J/J mice (M. musculus) that were administered approximately 50 sporulated oocysts of Hepatozoon americanum (AF176836) by gavage developed inflammatory lesions containing parasitic cystozoites in cardiac and skeletal muscle, kidney, and lung. Sprague-Dawley rats (Rattus norvegicus) similarly exposed showed no evidence of infection. Cystozoites were first detected by histopathologic examination four weeks after exposure to oocysts. Globular, PAS-positive material accumulated around the cystozoites as the duration of infection lengthened. Nested PCR analysis of tissues collected 16 weeks post-exposure was positive for the 18S rRNA Hepatozoon sp. gene and the DNA sequence of the fragment amplified was 99.6% and 99.8% identical to H. americanum sequences previously reported from naturally-infected dogs (AF176836 and AY864676, respectively). Merogonous and gamontogonous stages of the parasite were not detected in any of the cystozoite-infected rodents.     

Characterization of anti-channel catfish MHC class IIbeta monoclonal antibodies

This study characterizes four monoclonal antibodies (mAb) developed against the major histocompatibility complex (MHC) class II beta chain of the channel catfish, Ictalurus punctatus. Immunoprecipitations using catfish clonal B cells revealed that each of these mAbs immunoselected proteins of approximately 32 and 36 kD, which are of the appropriate sizes for MHC class II alpha and beta chains, respectively. Cell distribution studies using a fluorescence-activated cell sorter (FACS) combined with RT-PCR analyses demonstrated that MHC class II beta is expressed at a high density on catfish clonal macrophage, B and T cell lines, on alloantigen stimulated leukocytes, and on lipopolysaccharide-induced B-cell blasts. Collectively, these results demonstrate the potential importance of these antibodies as reagents in future studies dealing with the functional role of MHC class II molecules in immune recognition of self from non-self.     

Comparison of computer assisted surgery with conventional technique for treatment of abaxial distal phalanx fractures in horses: an in vitro study

Objective— To (1) evaluate and compare computer-assisted surgery (CAS) with conventional screw insertion (conventional osteosynthesis [COS]) for treatment of equine abaxial distal phalanx fractures; (2) compare planned screw position with actual postoperative position; and (3) determine preferred screw insertion direction.
Study design— Experimental study.
Sample population— Cadaveric equine limbs (n=32).
Methods— In 8 specimens each, a 4.5 mm cortex bone screw was inserted in lag fashion in dorsopalmar (plantar) direction using CAS or COS. In 2 other groups of 8, the screws were inserted in opposite direction. Precision of CAS was determined by comparison of planned and actual screw position. Preferred screw direction was also assessed for CAS and COS.
Results— In 4 of 6 direct comparisons, screw positioning was significantly better with CAS. Results of precision analysis for screw position were similar to studies published in human medicine. None of evaluated criteria identified a preferred direction for screw insertion.
Conclusion— For abaxial fractures of the distal phalanx, superior precision in screw position is achieved with CAS technique compared with COS technique.
Clinical Relevance— Abaxial fractures of the distal phalanx lend themselves to computer-assisted implantation of 1 screw in a dorsopalmar (plantar) direction. Because of the complex anatomic relationships, and our results, we discourage use of COS technique for repair of this fracture type.     

Simultaneous application of the vascular endothelial growth factor (VEGF) receptor inhibitor PTK787/ZK 222584 and ionizing radiation does not further reduce the growth of canine oral melanoma xenografts in nude mice

PTK787/ZK 222584 is an inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinases. In this study, the effectiveness of PTK787/ZK 222584 and radiation on canine oral melanoma xenografts was assessed. Xenografts were treated with radiotherapy (4x6Gy), or with PTK787/ZK 222584, or with a combination of both. Treatment efficacy was assessed using a tumour growth delay assay, serial power Doppler and pO(2) measurements during and after therapy. There was a significant growth delay for the group treated with radiation alone and for the combined treatment group. However, tumour growth delay was similar in both groups. Tumours were hypoxic before irradiation and no significant re-oxygenation occurred during therapy. In all tumours, vascularity and perfusion were significantly lower at the end of the study but no significant differences in perfusion, vascularity and oxygenation status were observed between and within treatment groups. The combination of PTK787/ZK 222584 and radiotherapy did not perform better than radiotherapy alone in this model.     

The Effect of Sedation on Gastric Emptying of a Liquid Marker in Ponies

OBJECTIVE: The effect of sedation on gastric emptying was evaluated in six ponies by monitoring serum concentrations of acetaminophen (AP) after intragastric administration. EXPERIMENTAL DESIGN: Prospective randomized experimental study. ANIMALS: Six adult ponies, 135 to 275 kg. METHODS: Fifteen minutes after the intravenous administration of xylazine (1 mg/kg), butorphanol (0.05 mg/kg), acepromazine (0.05 mg/kg) or saline, ponies were given AP (20 mg/kg in 350 mL water) by stomach tube. Blood for AP analysis was collected at baseline and 15, 30, 45, 75, 90, 105, and 120 minutes after AP administration. The time (Tmax) to reach peak serum concentration (Cmax), and the area under the AP serum concentration versus time curve (AUC) were determined for each treatment group. RESULTS: Tmax was 31 mins in the control group, and this increased significantly (P<.05) after sedation. Cmax decreased (P<.05) after xylazine administration, and AUC decreased (P<.05) after acepromazine. CONCLUSIONS: This study indicated that sedation has a significant effect on the gastric emptying rate of a liquid in ponies.     

Substrate composition determines emergence success and development of European nase larvae (Chondrostoma nasus L.)

European nase (Chondrostoma nasus) is a specialist riverine fish, characterised by a complex life cycle making it vulnerable to habitat degradation. Recent findings indicate that, analogously to salmonids, the interstitial zone quality may pose a serious bottleneck for successful recruitment of this species. In this study, nase eggs were exposed to different substrate qualities. First, standardised substrate mixtures with differing fine sediment additions were used. Second, we tested different homogenous gravel fractions for their influence on egg development and emergence success. In both setups, substrate composition significantly affected emergence success, timing of emergence and larvae size at emergence. In the substrate mixtures, emergence was most successful in substratum with no fine sediment addition (98%) and decreased to 55% in substratum with 20% fine sediment addition. Emergence was most successful in the coarsest fraction (93%) and decreased to 47% in the finest fraction. Over all treatments, the time between hatching and emergence from substrate differed by up to 156 degree days, thereby indicating that free embryos of nase use the shelter of the interstitial zone for early ontogeny. These results suggest that a loose and porous stream bed can positively contribute to the development success of eggs and larvae and thereby potentially improve the recruitment of nase populations. It is thus important to consider the substrate and interstitial conditions in the conservation and restoration management of this rheophilic cyprinid.     

Hydrolysed salmon meal as a replacement for salmon meal in practical diets for Pacific white shrimp (Litopenaeus vannamei)

A series of growth, feed stability and consumption trials were conducted to evaluate the efficacy of salmon by‐product in practical diets for Pacific white shrimp, Litopenaeus vannamei. This included a salmon by‐product meal (Salmon meal: SM) and a silage hydrolysate (hydrolysed salmon meal: HSM). The basal diet containing 120 g/kg SM was incrementally replaced (0. 25, 50, 75, 100%) by HSM to produce five test diets used in two trials. A sixth diet was included which evaluated gelatin supplementation (trial 1) or pH neutralization (trial 2). In trial 1, each diet was produced using two processing conditions (laboratory extruded and formed with meat grinder) and offered to shrimp in a clear water system. The results demonstrate that up to 50% of the SM can be used to replace with HSM; however, further increases resulted in reduced performance of shrimp. The addition of gelatin reduced leaching but there was limited effect of processing on leaching. There were no detectible effects of pH adjustment of the diets. Results indicated that the growth performance of shrimp has not influenced by HSM up to 60 g/kg to replace 50% of the SM in practical diets; however, higher levels resulted in significant decrease in performance.