The influence of rapid growth on sodium salicylate pharmacokinetics in male turkeys

The aim of this study was to assess the influence of growth on the pharmacokinetics of sodium salicylate (SS) in male turkeys. SS was administered intravenously at a dose of 50 mg/kg. Plasma drug concentrations were assessed by high‐performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental analysis. As the age increased from 6 to 13 weeks (body weight increase from 2.35 to 9.43 kg), median body clearance decreased from 1.34 to 0.87 ml/min/kg. This caused a significant increase in the median mean residence time from 3.42 to 4.44 hr. Elimination phase proved to be biphasic and two elimination half‐lives (T_1/2el) were distinguished. Whereas T_1/2el1 was found to increase with age by 128%, T_1/2el2 represented a later but faster and less age‐dependent phase of elimination (increase by 56% in the respective groups). Volume of distribution decreased with age. These effects may lead to different therapeutic response to SS in turkeys of different age and body weights.     

Stem cell factor supports migration in canine mesenchymal stem cells

Adult Mesenchymal Stem Cells (MSC) are cells that can be defined as multipotent cells able to differentiate into diverse lineages, under appropriate conditions. These cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Initially discovered in bone marrow, MSC can now be isolated from a wide spectrum of adult and foetal tissues. Studies to evaluate the therapeutic potential of these cells are based on their ability to arrive to damaged tissues. In this paper we have done a comparative study analyzing proliferation, surface markers and OCT4, SOX9, RUNX2, PPARG genes expression in MSC cells from Bone marrow (BMMSC) and Adipose tissue (ASC). We also analyzed the role of Stem Cell Factor (SCF) on MSC proliferation and on ASCs metalloproteinases MMP-2, MMP-9 secretion. Healthy dogs were used as BMMSC donors, and ASC were collected from omentum during elective ovariohysterectomy surgery. Both cell types were cultured in IMDM medium with or without SCF, 10% Dog Serum (DS), and incubated at 38 °C with 5% CO2. Growth of BMMSCs and ASCs was exponential until 25–30 days. Flow citometry of MSCs revealed positive results for CD90 and negative for CD34, CD45 and MCH-II. Genes were evaluated by RT-PCR and metalloproteinases by zymografy. Our findings indicate morphological and immunological similarities as well as expression of genes from both origins on analyzed cells. Furthermore, SCF did not affect proliferation of MSCs, however it up-regulated MMP-2 and MMP-9 secretion in ASCs. These results suggest that metalloproteinases are possibly essential molecules pivoting migration.     

Feeding behavior of feedlot lambs fed diets containing levels of cassava wastewater

In this study, we evaluated the effects of including cassava wastewater in the diet on the feeding behavior of feedlot lambs in 35 male uncastrated Santa Inês × Dorper crossbred lambs at an approximate age of 3 months, with an average live weight of 20.0?±?3.4 kg. Diets were formulated with hay of cassava shoots (roughage) and a concentrate based on corn and soybean, with a roughage:concentrate ratio of 50:50, plus inclusion of cassava wastewater at the levels of 0, 12, 24, 36, or 48 g/kg of the total diet. Feeding behavior was evaluated between the 46th and 52nd days of the experiment. Increasing cassava wastewater levels in the diet reduced (P?<?0.05) the intakes (kg/day) of dry matter and neutral detergent fiber as well as the efficiency of rumination (g/cud and g/h) of dry matter and neutral detergent fiber. The other behavioral parameters were not affected by wastewater inclusion in the diet. Therefore, the inclusion of up to 48 g/kg of cassava wastewater on fresh matter of diets is not recommended for feedlot lambs.     

Pharmacokinetic profiles of the two major active metabolites of metamizole (dipyrone) in cats following three different routes of administration

This study was performed to determine pharmacokinetic profiles of the two active metabolites of the analgesic drug metamizole (dipyrone , MET), 4‐methylaminoantipyrine (MAA), and 4‐aminoantipyrine (AA), after intravenous (i.v., intramuscular (i.m.), and oral (p.o.) administration in cats. Six healthy mixed‐breed cats were administered MET (25 mg/kg) by i.v., i.m., or p.o. routes in a crossover design. Adverse clinical signs, namely salivation and vomiting, were detected in all groups (i.v. 67%, i.m. 34%, and p.o. 15%). The mean maximal plasma concentration of MAA for i.v., i.m., and p.o. administrations was 148.63 ± 106.64, 18.74 ± 4.97, and 20.59 ± 15.29 μg/ml, respectively, with about 7 hr of half‐life in all routes. Among the administration routes, the area under the plasma concentration curve (AUC) value was the lowest after i.m. administration and the AUC_EV/i.v. ratio was higher in p.o. than the i.m. administration without statistical significance. The plasma concentration of AA was detectable up to 24 hr, and the mean plasma concentrations were smaller than MAA. The present results suggest that MET is converted into the active metabolites in cats as in humans. Further pharmacodynamics and safety studies should be performed before any clinical use.     

Effects of p.o. administered xylitol in cats

Xylitol is commonly used as sugar substitute in households. While it has numerous beneficial effects on human health, it is highly toxic to dogs. The goal of this study was to examine whether xylitol has similar deleterious effects, such as hypoglycaemia and acute hepatic failure, on cats. Our research included six healthy middle‐aged cats. Xylitol was dissolved in deionized water and administered p.o. at three doses (100, 500 and 1,000 mg/kg body weight). These dosages have been considered toxic and can cause liver failure or even death in dogs. After every xylitol administration, the basic health status and the blood glucose of cats were observed regularly. Additionally, prior to and 6, 24 and 72 hr after xylitol administration, blood samples were taken to check complete blood count, clinical biochemical parameters and enzymes such as ALT, ALKP, GGT, GLDH, bile acids, BUN, creatinine, phosphate, total protein, albumin, sodium and potassium. There were no significant changes (p > .05) in any of the haematological or biochemical parameters. Blood glucose concentrations did not show any significant alterations, except at 1,000 mg/kg dose, where a mild but significant increase was observed, but it was in physiological range. Based on our results, xylitol did not induce toxic effects on cats.     

The construction and application of a population physiologically based pharmacokinetic model for methadone in Beagles and Greyhounds

Methadone is an opioid analgesic in veterinary and human medicine. To help develop appropriate pain management practices and to develop a quantitative model for predicting methadone dosimetry, a flow‐limited multiroute physiologically based pharmacokinetic (PBPK) model for methadone in dogs constructed with Berkeley Madonna? was developed. The model accounts for intravenous (IV), subcutaneous (SC), and oral administrations, and compartmentalizes the body into different components. This model was calibrated from plasma pharmacokinetic data after IV administration of methadone in Beagles and Greyhounds. The calibrated model was evaluated with independent data in both breeds of dogs. One advantage of this model is that most physiological parameter values for Greyhounds were taken directly from the original literature. The developed model simulates available pharmacokinetic data for plasma concentrations well for both breeds. After conducting regression analysis, all simulated datasets produced an R ² > 0.80 when compared to the measured plasma concentrations. Comparative analysis of the dosimetry of methadone between the breeds suggested that Greyhounds had ~50% lower 24‐hr area under the curve (AUC) of plasma or brain concentrations than in Beagles. Furthermore, population analysis was conducted with this study. This model can be used to predict methadone concentrations in multiple dog breeds using breed‐specific parameters.