This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Exposure of infants and consumers to drugs and environmental toxins through breast or cows'milk is an ongoing concern. There is a need for valid in vitro models to determine the rate and extent to which chemicals are excreted in milk and to study the mechanisms by which chemicals cross this epithelial barrier. Cultured bovine mammary epithelial monolayers (BME-UV) mounted in flow-through diffusion chambers are used to determine the flux of a range of drugs across the mammary epithelial monolayer, testing for, and quantifying, the contribution of carrier-mediated transport processes. The relationship between the drugs'permeability across the BME-UV monolayer and their milk clearance will be determined by conducting in vivo pharmacokinetic studies in lactating dairy cattle. Results from these studies are essential to determine if the BME-UV cell line is suitable as an in vitro model to study the excretion of xenobiotics through cows'milk. The results are also needed as a foundation for future molecular studies to compare the expression of drug transporters in vitro, in vivo and between species. Ultimately, the goal will be to refine the model through a combination of selecting appropriate cell lines and biotechnology so that a system is developed that accurately predicts in vivo outcomes for specific species of interest. Such a model offers the opportunity to conduct studies with the aim of identifying, assessing and mitigating risks to human health posed by exposure to potentially harmful xenobiotics through human and cow's milk.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017686-10
Application #
8360339
Study Section
Special Emphasis Panel (ZRR1-RI-5 (01))
Project Start
2011-07-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2011
Total Cost
$180,679
Indirect Cost
Name
Kansas State University
Department
Anatomy/Cell Biology
Type
Schools of Veterinary Medicine
DUNS #
929773554
City
Manhattan
State
KS
Country
United States
Zip Code
66506
Honda, Keiji; Kim, Sung Huhn; Kelly, Michael C et al. (2017) Molecular architecture underlying fluid absorption by the developing inner ear. Elife 6:
Miyazaki, Hiromitsu; Wangemann, Philine; Marcus, Daniel C (2016) The gastric H,K-ATPase in stria vascularis contributes to pH regulation of cochlear endolymph but not to K secretion. BMC Physiol 17:1
Krishnamoorthy, Gayathri; Reimann, Katrin; Wangemann, Philine (2016) Ryanodine-induced vasoconstriction of the gerbil spiral modiolar artery depends on the Ca(2+) sensitivity but not on Ca(2+) sparks or BK channels. BMC Physiol 16:6
Montero-AstĂșa, Mauricio; Ullman, Diane E; Whitfield, Anna E (2016) Salivary gland morphology, tissue tropism and the progression of tospovirus infection in Frankliniella occidentalis. Virology 493:39-51
Dib, Lea H; Ortega, M Teresa; Melgarejo, Tonatiuh et al. (2016) Establishment and characterization of DB-1: a leptin receptor-deficient murine macrophage cell line. Cytotechnology 68:921-33
Ishiguro, Susumu; Yoshimura, Kiyoshi; Tsunedomi, Ryouichi et al. (2015) Involvement of angiotensin II type 2 receptor (AT2R) signaling in human pancreatic ductal adenocarcinoma (PDAC): a novel AT2R agonist effectively attenuates growth of PDAC grafts in mice. Cancer Biol Ther 16:307-16
Ohta, Naomi; Ishiguro, Susumu; Kawabata, Atsushi et al. (2015) Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes. PLoS One 10:e0123756
Peng, Zeyu; Dittmer, Neal T; Lang, Minglin et al. (2015) Multicopper oxidase-1 orthologs from diverse insect species have ascorbate oxidase activity. Insect Biochem Mol Biol 59:58-71
Mao, Xiuli; Zhang, Yuntao; Schwend, Tyler et al. (2015) Effects of polysialic acid on sensory innervation of the cornea. Dev Biol 398:193-205
Sang, Yongming; Rowland, Raymond R R; Blecha, Frank (2014) Antiviral regulation in porcine monocytic cells at different activation states. J Virol 88:11395-410

Showing the most recent 10 out of 202 publications