Pharmacokinetic indices for cefovecin after single‐dose administration to adult sea otters (Enhydra lutris)

Seven sea otters received a single subcutaneous dose of cefovecin at 8 mg/kg body weight. Plasma samples were collected at predetermined time points and assayed for total cefovecin concentrations using ultra‐performance liquid chromatography and tandem mass spectrometry. The mean (±SD) noncompartmental pharmacokinetic indices were as follows: C_Max (obs) 70.6 ± 14.6 μg/mL, T_{Max (obs)} 2.9 ± 1.5 h, elimination rate constant (k_el) 0.017 ± 0.002/h, elimination half‐life (t_1/2kel) 41.6 ± 4.7 h, area under the plasma concentration‐vs.‐time curve to last sample (AUC_last) 3438.7 ± 437.7 h·μg/mL and AUC extrapolated to infinity (AUC_0→∞) 3447.8 ± 439.0 h·μg/mL. The minimum inhibitory concentrations (MIC) for select isolates were determined and used to suggest possible dosing intervals of 10 days, 5 days, and 2.5 days for gram‐positive, gram‐negative, and Vibrio parahaemolyticus bacterial species, respectively. This study found a single subcutaneous dose of cefovecin sodium in sea otters to be clinically safe and a viable option for long‐acting antimicrobial therapy.     

Effect of maternal cells transferred with colostrum on cellular responses to pathogen antigens in neonatal calves

OBJECTIVE: To assess the effect of maternal cells or cellular components on neonatal immune responses to intracellular pathogens in calves. ANIMALS: 15 Holstein calves. PROCEDURES: Calves were fed whole colostrum, frozen colostrum, or cell-free colostrum within 4 hours after birth. Leukocytes were obtained from calves before feeding colostrum and 1, 2, 7, 14, 21, and 28 days after ingestion. Proliferative responses against bovine viral diarrhea virus (BVDV) and mycobacterial purified protein derivatives were evaluated. Dams received a vaccine containing inactivated BVDV, but were not vaccinated against mycobacterial antigens. RESULTS: All calves had essentially no IgG in circulation at birth, but comparable and substantial concentrations by day 1. Calves that received whole colostrum had enhanced responses to BVDV antigen 1 and 2 days after ingestion of colostrum. In contrast, calves that received frozen colostrum or cell-free colostrum did not respond to BVDV. No differences were identified among the 3 groups in response to mycobacterial antigens. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that transfer of live maternal cells from colostrum to neonatal calves enhanced responses to antigens against which the dams had previously responded (BVDV), but not to antigens to which the dams were na?ve (mycobacterial purified protein derivatives). Results suggested that cell-mediated immune transfer to neonates can be enhanced by maternal vaccination.     

Resynchronization of estrus in beef cattle: ovarian function, estrus and fertility following progestin treatment and treatments to synchronize ovarian follicular development and estrus

The objective was to optimize rebreeding of nonpregnant, previously inseminated beef cattle. In Experiment 1, 43 cows received a used intravaginal progesterone-releasing insert (IVPRI; Days 0-7) 12.3 d after ovulation and received concurrently no treatment, 100 microg gonadotropin releasing hormone (GnRH), 1 mg estradiol cypionate (ECP), or 150 mg progesterone. Emergence of a new ovarian follicular wave was most synchronous (P < 0.0001) in the GnRH group. In Experiment 2, 675 heifers were given GnRH or no treatment on Day 0, fed melengestrol acetate (MGA; 0.5 mg/head/d) from Days 0-5 (Day 0 = 13-14 d after timed insemination; TAI), given 0.5 mg ECP or nothing on Day 7, and reinseminated 6-12 h after onset of estrus. Estrus was more synchronous (P < 0.05) in heifers given GnRH versus no treatment on Day 0. In Experiment 3, 317 TAI heifers were resynchronized with either MGA or a used IVPRI with or without ECP on Day 7; estrus was more synchronous (P < 0.05) and pregnancy rates were higher (54.1% versus 39.2%, P < 0.05) in heifers given a used IVPRI than those fed MGA. For resynchronization of heifers, pregnancy rates were not significantly improved with GnRH treatment, but were higher with a used IVPRI than with MGA.     

Scintigraphic examination of the cartilages of the foot

REASONS FOR PERFORMING STUDY: Radiographic examination of the cartilages of the foot is well documented; however, there is limited information about their scintigraphic assessment. OBJECTIVES: To evaluate the scintigraphic appearance of the cartilages of the foot using subjective and quantitative image analysis and to correlate radiographic and scintigraphic findings. HYPOTHESES: An ossified cartilage would have similar radiopharmaceutical uptake (RU) to the ipsilateral aspect of the distal phalanx; RU would extend throughout the length of the ossified cartilage; a separate centre of ossification (SCO) would be identified on a scintigraphic image; and fracture or trauma to an ossified cartilage would manifest as increased RU (IRU). METHODS: Front feet (n = 223) of horses (n = 186) that had dorsopalmar radiographic views and dorsal scintigraphic images were included in the study. The cartilages of the foot were graded radiographically and scintigraphically. Quantitative evaluation of the scintigraphic images was carried out using region of interest (ROI) analysis. For statistical analysis RU ratios were used. Correlations between a radiographically detected SCO and focal RU and between IRU and radiographic abnormalities were assessed. RESULTS: There was a good correlation and an excellent agreement between radiographic and scintigraphic grades. ROI analysis showed a proximal to distal increase in RU ratios within each cartilage of the foot. A radiographically identified SCO could be detected scintigraphically in 12/17 feet (70.6%). Thirty-eight feet had IRU in the region of a cartilage, 25 of which (65.8%) had corresponding radiographic abnormalities. Fracture of an ossified cartilage was associated with IRU in all horses. CONCLUSIONS AND POTENTIAL RELEVANCE: Scintigraphy may give information about the potential clinical significance of ossification of the cartilages of the foot and associated lesions, therefore prompting further investigation by use of a uniaxial ipsilateral palmar nerve block and imaging, using either magnetic resonance imaging and/or computed tomography.     

The second-generation curcumin analogue RL71 elicits G2/M cell cycle arrest and apoptosis in canine osteosarcoma cells

Canine osteosarcoma is an aggressive cancer, comprising 85% of canine bone neoplasms. Current treatment practices of surgery and chemotherapy increase 1-year survival by only 45%. The curcumin analogue RL71, has demonstrated potent in vitro and in vivo efficacy in several models of human breast cancer through increased apoptosis and cell cycle arrest. Thus, the present study aimed to investigate efficacy of curcumin analogues in two canine osteosarcoma cell lines. Osteosarcoma cell viability was assessed using the sulforhodamine B assay and mechanisms of action were determined by analysing the levels of cell cycle and apoptotic regulatory proteins via Western blotting. Further evidence was obtained using flow cytometry to detect cell cycle distribution and the number of apoptotic cells. RL71 was the most potent curcumin analogue with EC₅₀ values of 0.64 ± 0.04 and 0.38 ± 0.009 μM (n = 3) in D-17 (commercial) and Gracie canine osteosarcoma cells, respectively. RL71 significantly increased the ratio of cleaved-caspase 3 to pro-caspase 3 and the level of apoptotic cells at the 2× and 5× EC₅₀ concentration (p < 0.001, n = 3). Furthermore, at the same concentration, RL71 significantly increased the number of cells in the G2/M phase. In conclusion, RL71 has potent cytotoxic activity in canine osteosarcoma cells triggering G2/M arrest and apoptosis at concentrations achievable in vivo. Future research should further investigate molecular mechanisms for these changes in other canine osteosarcoma cell lines prior to in vivo investigation.     

Potential farmer contributions to the design process: Indications from Indonesia

The paper argues that conventional irrigation design processes rely heavily on predetermined design criteria, often without allowing for interactions with farmers and revising of criteria during implementation. Six cases from a tertiary development project in North Sulawesi, Indonesia are described, where farmers altered what had been designed and constructed by contracting and agency engineers. Through field inspections and farmer interviews, the farmers' alternative set of design criteria was elicited to explain why the farmers changed what had been constructed. A total of 27 cases are analyzed to show the relative importance of: