Pharmacokinetics of Single-bolus Subcutaneous Cefovecin in C57BL/6 Mice.

Because of its extended half-life, cefovecin is a broad-spectrum cephalosporin antibiotic commonly used to treat dermatitis in dogs and cats. A single injection in dogs can yield an effective plasma concentration for as long as 14 d, depending on the strain of Staphylococcus and for as long as 7 d in cats for the treatment of Pasteurella multocida. In the laboratory animal setting, C57BL/6 mice are commonly affected with dermatologic conditions that make these animals unsuitable for experiments. Therefore, we performed this pharmacokinetic study to determine whether cefovecin would be of benefit in mice. Plasma levels of the drug were determined by HPLC. For this study, single-bolus subcutaneous dosages of 8 and 40 mg/kg were assessed. The results showed that the dosage of 40 mg/kg achieved a maximal plasma concentration of 411.54 µg/mL with a half-life of 0.84 h, whereas 8 mg/kg yielded 78.18 µg/mL and 1.07 h respectively. The pharmacokinetic results suggest that cefovecin is not suitable as a long-acting antibiotic after a single subcutaneous bolus injection in mice for the treatment of dermatitis or any other bacteria sensitive to this medication.

Common marmoset (Callithrix jacchus) as a primate model for behavioral neuroscience studies.

BACKGROUND: The common marmoset (Callithrix jacchus) has been proposed as a suitable bridge between rodents and larger primates. They have been used in several types of research including auditory, vocal, visual, pharmacological and genetics studies. However, marmosets have not been used as much for behavioral studies. NEW METHOD: Here we present data from training 12 adult marmosets for behavioral neuroscience studies. We discuss the husbandry, food preferences, handling, acclimation to laboratory environments and neurosurgical techniques. In this paper, we also present a custom built "scoop" and a monkey chair suitable for training of these animals. RESULTS: The animals were trained for three tasks: 4 target center-out reaching task, reaching tasks that involved controlling robot actions, and touch screen task. All animals learned the center-out reaching task within 1-2 weeks whereas learning reaching tasks controlling robot actions task took several months of behavioral training where the monkeys learned to associate robot actions with food rewards. COMPARISON TO EXISTING METHOD: We propose the marmoset as a novel model for behavioral neuroscience research as an alternate for larger primate models. This is due to the ease of handling, quick reproduction, available neuroanatomy, sensorimotor system similar to larger primates and humans, and a lissencephalic brain that can enable implantation of microelectrode arrays relatively easier at various cortical locations compared to larger primates. CONCLUSION: All animals were able to learn behavioral tasks well and we present the marmosets as an alternate model for simple behavioral neuroscience tasks.

Choice of immunosuppression influences cytomegalovirus DNAemia in cynomolgus monkey (Macaca fascicularis) islet allograft recipients.

This retrospective study reviews the results of our experience with the occurrence of CMV DNAemia in islet cell transplanted cynomolgus monkeys subjected to different immunosuppressive protocols, including induction treatment with thymoglobulin (TMG), with a combination of thymoglobulin and fludarabine (FLUD), with cyclophosphamide, or with daclizumab. CMV DNA in the peripheral blood (CMV DNAemia) of 47 monkeys was quantified by real-time PCR on a weekly to biweekly basis. As compared to other immunosuppressive regimens, and in association with greater decreases in WBC, lymphocyte, CD3+CD4+, and CD3+CD8+ lymphocyte counts, frequent CMV DNAemia occurred earlier (within the first month posttransplant), and was of greater severity and duration in recipients of TMG ± FLUD. Treatment of recipients with alternative induction agents that resulted in less dramatic reductions in WBC and lymphocyte counts, however, resulted in occurrence of CMV DNAemia after postoperative day 60. The frequency, average intensity, duration, and area under the curve (AUC) for CMV DNAemia in animals receiving TMG ± FLUD were 75-100%, 4.02 ± 1.75 copies/ng DNA, 23.0 ± 5.3 days, and 367.0 ± 121.1 days × copies/ng DNA, respectively; corresponding values in animals receiving other treatments (0-44%, 0.19 ± 0.10 copies/ng DNA, 0.5 ± 0.3 days, and 75.4 ± 40.2 days × copies/ng DNA, respectively) were significantly different. The value of WBC, T and B cells at the nadir of cell depletion greatly affects the occurrence of CMV DNAemia. No animals developed CMV DNAemia within the next 3 weeks when the lowest value of WBC, lymphocyte, CD3+, CD3+CD4+, CD3+CD8+, or CD20+ cells was above 4500, 1800, 300, 200, 150, or 300 cells/µl, respectively. Oral valganciclovir prophylaxis did not completely prevent the appearance of CMV DNAemia.