Guanidinoacetic acid supplementation in broiler chickens fed on corn-soybean diets affects performance in the finisher period and energy metabolites in breast muscle independent of diet nutrient density

(1) Guanidinoacetic acid (GAA) is the single immediate endogenous precursor of creatine (Cr). It was hypothesised that dietary GAA would have different effects on performance and energy metabolites in breast muscle depending on the nutrient density (ND) of corn-soybean-based diets.

(2) A total of 540 one-day-old male Ross 308 broilers were allocated to 9 dietary treatments with 6 replicates (10 birds each) in a 3 × 3 factorial arrangement with three levels of ND (low, 2800; medium, 2950 and high, 3100 kcal metabolizable energy (ME)/kg; and with the other nutrients being constant relative to ME) and supplemented with three levels of GAA (0, 0.6 and 1.2 g/kg) in a 42-d feeding trial.

(3) In the starter and grower periods, increasing levels of ND improved body weight (BW), average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR), with the exception of ADFI in the starter period. GAA supplementation did not affect performance characteristics. All performance indicators responded markedly to increasing ND in the finisher period, whereas the highest GAA level reduced ADFI compared to the unsupplemented control (156 vs. 162 g/d) and concomitantly FCR (1.81 vs. 1.93). No interactive effects were noted for any performance trait. The high ND diet resulted in more breast meat yield on d42, associated with higher fat content and darker colour compared to the other ND levels. The GAA supplementation did not affect carcass and breast traits. At the end of the experiment, Cr was elevated when feeding GAA at 1.2 g/kg (5455 vs. 4338 mg/kg fresh muscle).

(4) To conclude, ND had a substantial effect on performance and carcass traits, whereas any effect of GAA was limited to FCR in the finisher period and independent of diet ND level.     

Efficacy of a mephentermine‐based product as a vasopressor and a cardiac performance enhancer when given intramuscularly to cattle

The goal of this study was to confirm the vasopressor and cardiac effects of POTENAY^® INJETÁVEL (POT), a mephentermine‐based product, given to cattle with induced vascular/cardiac depression. Ten healthy Holstein cattle (206 ± 13 kg) followed a randomized‐complete‐block design (RCBD) utilizing crossover study design. Each animal randomly received (1 ml/25 kg, IM) of either POT (n = 10) or volume‐matched placebo control (0.9%NaCl, CP, n = 10). A subset of animals (n = 5) received POT first (day 0) while the remaining (n = 5) received CP; after a six‐day washout period, cattle received the opposite compound. Animals were anesthetized and catheterized for systemic/left ventricular hemodynamic monitoring. Myocardial dysfunction/hypotension was induced by increasing the end‐tidal isoflurane concentration until arterial blood pressure was 20% lower than at baseline and remained stable. Once the animal was determined to be hypotensive and hemodynamically stable, steady‐state hypotensive baseline data (BL2) were acquired, and treatment with either POT or CP was given. Data were acquired post‐treatment at every 15 min for 90 min. POT improved cardiac output (+68 L/min, ±14%, p < 0.05), MAP (+14 mmHg, ±4%, p < 0.05), HR (+22 bpm, ±8%, p < 0.05), and peak rates of ventricular pressure change during both systole (dP/dt_max: +37 mmHg/s ±13%, p < 0.05) and diastole (dP/dt_min: +31 mmHg/s, ±7%, p < 0.05). No improvements were noted following placebo‐control administration. Results indicate that POT improves cardiac performance and systemic hemodynamics in cattle with induced cardiovascular depression when given as single intramuscular injection.     

Comparison of the pharmacokinetic profiles of two different amphotericin B formulations in healthy dogs

This study was conducted to compare the pharmacokinetic profiles of conventional (Fungizone^®) and liposomal amphotericin B (AmBisome^®) formulations in order to predict their therapeutic properties, and evaluate their potential differences in veterinary treatment. For this purpose, twelve healthy mixed breed dogs received both drugs at a dose of 0.6 mg/kg by intravenous infusion over a 4‐min period in a total volume of 40 ml. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72 and 96 hr after dosing, and concentrations of drug in plasma were determined by high‐performance liquid chromatography (HPLC). Pharmacokinetics was described by a two‐compartment model. Although both formulations were administered at the same doses (0.6 mg/kg), the plasma pharmacokinetics of liposomal amphotericin B differed significantly from those of amphotericin B deoxycholate in healthy dogs (p < .05). Liposomal amphotericin B showed markedly higher peak plasma concentrations (approximately ninefold greater) and higher area under the plasma concentration curve values (approximately 14‐fold higher) compared to conventional formulation. It is concluded that AmBisome^® reached higher plasma concentration and lower distribution volume and had a longer half‐life compared to Fungizone^®, and therefore, AmBisome^® is reported to be an appropriate and effective choice for the treatment of systemic mycotic infections in dogs.     

Effect of dasatinib in a xenograft mouse model of canine histiocytic sarcoma and in vitro expression status of its potential target EPHA2

Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, EPHA2 was only weakly detected in all HS cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting EPHA2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine HS.     

Review of triazine antiprotozoal drugs used in veterinary medicine

Triazines are relatively new antiprotozoal drugs that have successfully controlled coccidiosis and equine protozoal myeloencephalitis. These drugs have favorably treated other protozoal diseases such as neosporosis and toxoplasmosis. In this article, we discuss the pharmacological characteristics of five triazines, toltrazuril, ponazuril, clazuril, diclazuril, and nitromezuril which are used in veterinary medicine to control protozoal diseases which include coccidiosis, equine protozoal myeloencephalitis, neosporosis, and toxoplasmosis.