Pharmacokinetics of sanguinarine,chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half‐life (t_1/2) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (C_max) of DHSA (2.49 ± 1.4 μg/L) was higher that of SA (1.89 ± 0.8 μg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h^?1·kg^?1) with a t_1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.     

Employing a Monte Carlo algorithm in expectation maximization restricted maximum likelihood estimation of the linear mixed model

Multiple‐trait and random regression models have multiplied the number of equations needed for the estimation of variance components. To avoid inversion or decomposition of a large coefficient matrix, we propose estimation of variance components by Monte Carlo expectation maximization restricted maximum likelihood (MC EM REML) for multiple‐trait linear mixed models. Implementation is based on full‐model sampling for calculating the prediction error variances required for EM REML. Performance of the analytical and the MC EM REML algorithm was compared using a simulated and a field data set. For field data, results from both algorithms corresponded well even with one MC sample within an MC EM REML round. The magnitude of the standard errors of estimated prediction error variances depended on the formula used to calculate them and on the MC sample size within an MC EM REML round. Sampling variation in MC EM REML did not impair the convergence behaviour of the solutions compared with analytical EM REML analysis. A convergence criterion that takes into account the sampling variation was developed to monitor convergence for the MC EM REML algorithm. For the field data set, MC EM REML proved far superior to analytical EM REML both in computing time and in memory need.     

Disposition of plasma creatinine in non-azotaemic and moderately azotaemic cats

The objectives of this study were to compare assay methods for plasma creatinine (Pl-creat) in cats and to describe the disposition of creatinine and iohexol in 12 healthy and moderately azotaemic cats. Exogenous creatinine and iohexol were injected simultaneously by intravenous bolus, and repeated blood samples were taken to determine the pharmacokinetic parameters of each marker. Pl-creat was assayed by high-performance liquid chromatography (HPLC), Jaffé and enzymatic methods. The enzymatic method was shown to be more reliable than the Jaffé method. Two stereoisomers, exo- and endo-iohexol were identified. The plasma clearance of creatinine (2.3+/-0.66 ml/min/kg) was significantly higher (P<0.001) than that of exo-iohexol (1.7+/-0.40 ml/min/kg). The volume of distribution (447+/-97 ml/kg) and elimination half-life (181+/-77 min) of creatinine were also higher (P<0.001) than those of exo- and endo-iohexol. The estimated daily endogenous production of creatinine was 65+/-23 mg/kg. None of the pharmacokinetic parameters was changed by the azotaemic status of the animals.     

Evaluation of transformation growth factor beta1, interleukin-10, and interferon-gamma in male symptomatic and asymptomatic dogs naturally infected by Leishmania (Leishmania) chagasi

The aims of this study were to evaluate the immunomodulatory role of TGF-β₁, IL-10, and INF-γ in spleen and liver extracts and supernatant cultures of white spleen cells from male symptomatic and asymptomatic dogs, naturally infected by Leishmania (Leishmania) chagasi. Thirty dogs from Araçatuba, São Paulo, Brazil, an endemic leishmaniosis area, were selected by positive ELISA serological reaction for Leishmania sp. and divided into two groups: asymptomatic (n = 15) and symptomatic (n = 15) consisting of animals with at least three characteristic signs (fever, dermatitis, lymphoadenopathy, onychogryphosis, weight loss, cachexia, locomotion problems, conjunctivitis, epistaxis, hepatosplenomegaly, edema, and apathy). After euthanasia, spleen and liver fragments were collected for ex vivo quantification of TGF-β₁, IL-10, and INF-γ. Naturally active in vitro produced TGF-β₁ was also evaluated in spleen cell culture supernatant. Spleen and liver extract of asymptomatic dogs had higher mean TGF-β₁ levels than symptomatic dogs. High concentrations of IL-10 were found in spleen, and mainly in liver extract of both groups. Higher INF-γ concentrations were found in spleen extracts of symptomatic dogs, and in liver extracts of asymptomatic dogs. Extract of this cytokine was lower in spleen extract. Although INF-γ is being produced in canine infection, mean levels of TGF-β₁ and IL-10 from spleen and liver extracts were quantitatively much higher; suggesting that immune response in both asymptomatic and symptomatic dogs was predominantly type Th2.     

Meal size and starch content affect gastric emptying in horses

REASONS FOR PERFORMING STUDY: Feeding practices have been associated with colic in horses. If meal size and composition have an effect on gastric emptying, this could be one of the mechanisms by which feeding practices are related to the occurrence of colic. OBJECTIVES: To evaluate the effect of meal size and starch content on solid phase gastric emptying. METHODS: Solid phase gastric emptying of 3 different radiolabelled meals, small low-starch (SmLS), small high-starch (SmHS) and large high-starch (LgHS) meals, was measured in 5 horses by scintigraphy using 99mTc-disofenin. Data were compared among meals using nonlinear mixed-effects models and paired t tests. RESULTS: On a percentage basis, SmHS emptied significantly faster than LgHS and SmLS emptied significantly faster than SmHS meals. However, when meals of unequal size were compared by emptying rate in g/min and Kcal/min, LgHS emptied significantly faster than SmHS. CONCLUSIONS: Meal size and composition affect gastric emptying. POTENTIAL RELEVANCE: Further work needs to be performed in order to substantiate the possibility of a relationship between digestive functions and occurrence of colic and gastric ulcers.     

Characterization of biological activities of feline eosinophil granule proteins

OBJECTIVE:To characterize eosinophil granule-derived proteins in cats. SAMPLE POPULATION: Eosinophils collected via peritoneal lavage from 2 cats. PROCEDURE: The cats were infested orally with Toxocara canis eggs and subsequently challenge-exposed with T. canis antigen injected IP to induce peritoneal eosinophilia; eosinophils were collected via peritoneal lavage. Eosinophil granule proteins were acid-extracted, separated by gel-filtration chromatography, and examined for their peroxidase, ribonuclease, and bactericidal activities; the N-terminal sequence of some of these proteins was determined and compared with homologue proteins from other species. RESULTS: 3 protein peaks were separated in the chromatogram. The first peak had both peroxidase and bactericidal activities. The second peak had ribonuclease and bactericidal activities, and the N-terminal sequence of the major protein was homologous with that of proteins of the ribonuclease A superfamily, including eosinophil ribonucleases from humans and other animal species. The third protein peak had bactericidal activity, and the N-terminal sequence of the major protein was homologous with that of human and murine major basic proteins. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that feline eosinophil granules contain major basic protein and eosinophil-associated ribonuclease and the granule proteins have peroxidase, ribonuclease, and bactericidal activities. In cats, characterization of eosinophil granule proteins may be useful in elucidation of the mechanism of tissue damage in eosinophil-associated diseases and development of new treatment options for those diseases. In addition, the identification of conserved structure and function of eosinophil granule proteins in cats is relevant from an evolutionary viewpoint.     

Development of an Immunobinding Assay with Monoclonal Antibodies to Diagnose Mycoplasma bovis in Semen

Veterinary Research Communications -     

Bovine herpesvirus 1 glycoprotein D expression in bovine upper respiratory tract mediated by a human adenovirus type 5

Bovine herpesvirus 1 glycoprotein D (gD) gene expression by recombinant replication defective human adenovirus type 5 (HAdV-5) was investigated in calves using indirect immunofluorescence microscopy (IIFM), confocal laser scanning microscopy (CLSM) and RT-PCR. One fold intranasal instillation of HAdV-5-expressing gD in the cattle upper respiratory tract showed a short term expression of at least 5 days, but not 10 days, limited only to epithelial cells localised in the epithelium of the nasal mucosa in one out of six calves. Observed limited gene transfer into well differentiated cattle airway epithelial cells must be taken into consideration in order to enhance transfection efficiency, and consequently the vaccine potential of this vector.