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Jogeshwari, India

Hu S.X.,Zoetis Inc.
Poultry Science | Year: 2013

Age has significant impact on hepatic cytochrome P450 (CYP450) systems in animals. Ross 708 broiler chicken is a breed of chicken with fast growth characteristics. Cytochrome P450 in the livers of Ross 708 broiler chicken of different ages has been investigated. The birds were raised under standard husbandry conditions. A certain number of chickens was randomly sampled weekly for liver collection from d 1 to 56 posthatch. The chicken body and liver weights were recorded. The chicken livers were processed for liver microsomes though a multiple-step procedure at low temperature. Total CYP450 content in chicken liver homogenates and liver microsomes was measured using a UV/visible spectroscopic method. The enzymatic activities of CYP450 in the chicken liver microsomes were determined through incubation of CYP450 isoform substrates followed by measurement of formation of their metabolites. The chicken showed an opposite age pattern in hepatic CYP450 content and activities compared with most mammals. The hepatic CYP450 content and activities of chicken at d 1 posthatch were higher than at other ages. The total hepatic CYP450 content in chickens at d 1 posthatch was more than twice the average hepatic value of the chickens at d 7 to 28. This high CYP450 fell quickly in the first week posthatch and slightly rose from d 28 to 56. Hepatic CYP450 activities of CYP1A, 3A, 2C, 2D, and 2H were much higher in the chicken at d 1 posthatch. The differences of these enzymatic activities between d 1 and other ages of chicken were CYP450 isoform dependent. This result suggests that embryonic development of chicken livers has a significant impact on the age profile of hepatic CYP450 content and activities of posthatch chickens. © 2013 Poultry Science Association Inc. Source


Hu S.X.,Zoetis Inc.
Journal of Veterinary Pharmacology and Therapeutics | Year: 2015

Swine is not only an important species in veterinary medicine research but also a popular animal model for human drug discovery. It is valuable to understand the impact of pig age on abundance and activity of porcine hepatic cytochrome P450 (CYP450). Liver microsomes were prepared from Camborough-29 intact male pigs at the age of 1 day and 2 weeks and the castrated male pigs at the age of 5, 10, and 20 weeks. Hepatic CYP450 content in the liver microsomes was measured using a UV/visible spectroscopic method. The activities of CYP450s were evaluated by metabolism of phenacetin, coumarin, tolbutamide, bufuralol, chlorzoxazone, and midazolam. The porcine hepatic CYP450 content increased with age with a plateau between age 2 and 5 weeks. Activities of all CYP450 enzymes increased with age of pigs too. The bufuralol 1'-hydroxylase showed the highest hepatic activities compared with other CYP enzymes at all ages of pigs. The average activities at the age of 20 weeks were about five times higher than those at the age of 5 weeks for most of the CYP enzymes. With compensation of the ratio of liver to body weights, the overall CYP450 metabolism capability of the pigs may be peaked around ages of 10 to 20 weeks. Those findings suggest that metabolism can be significantly different in growing phase of pigs and that the age may be an important factor in porcine medicine evaluation and pig model development. © 2014 John Wiley & Sons Ltd. Source


Trible B.R.,Kansas State University | Popescu L.N.,Kansas State University | Monday N.,Kansas State University | Calvert J.G.,Zoetis Inc. | Rowland R.R.R.,Kansas State University
Journal of Virology | Year: 2015

Assessment of virus neutralization (VN) activity in 176 pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) identified one pig with broadly neutralizing activity. A Tyr-10 deletion in the matrix protein provided escape from broad neutralization without affecting homologous neutralizing activity. The role of the Tyr-10 deletion was confirmed through an infectious clone with a Tyr-10 deletion. The results demonstrate differences in the properties and specificities of VN responses elicited during PRRSV infection. © 2015, American Society for Microbiology. All Rights Reserved. Source


Villarino N.,University of Tennessee at Knoxville | Brown S.A.,Zoetis Inc. | Martin-Jimenez T.,University of Tennessee at Knoxville
Journal of Veterinary Pharmacology and Therapeutics | Year: 2014

Tulathromycin is approved in the United States for the treatment of respiratory disease in bovine and swine, infectious bovine keratoconjunctivitis associated with Moraxella bovis, and interdigital necrobacillosis in bovine. This macrolide highly concentrates in lung tissue and persists in the intra-airway compartment for a long time after a single administration. It also accumulates in inflammatory cells, including neutrophils and macrophages. This article reviews pharmacokinetic information about tulathromycin in different veterinary species with particular emphasis on the respiratory system. © 2013 John Wiley & Sons Ltd. Source


Subramanian G.,Zoetis Inc. | Rao S.N.,Rutgers University
Bioorganic and Medicinal Chemistry Letters | Year: 2013

The performance of several structure-based design (SBD) approaches in predicting the binding affinity of diverse small molecule inhibitors co-crystallized to human renin was assessed to ascertain the modeling tool and method of choice required when dealing with structure-based lead optimization projects. Most of the SBD approaches investigated here were able to provide qualitative guidance, but quantitative accuracy as well as decisive discrimination between [in]actives is still not within reach. Such an outcome suggests that the current methods need improvement to capture the overall physics of the binding phenomenon for consistent applications in a lead optimization setting. © 2013 Elsevier Ltd. All rights reserved. Source

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