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Modulation of Immune-GI Function by NanoAg

纳米银对免疫胃肠道功能的调节

基本信息

批准号：
8393974
负责人：
MARTIN A. PHILBERT
金额：
$ 4.77万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-24 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8393974
关键词：
Address Animal Model Animals Antibiotics Benchmarking Blood Caliber Chemicals Clinical Collaborations Collection Computer software Contracts Data Data Set Databases Dendritic Cells Development Dose Drug Kinetics Drug or chemical Tissue Distribution Ecology Engineering Enteral Environmental Risk Factor Epithelial Epithelial Cells Fixatives Formalin Freezing Future Glutaral Gold Health Human Immunologics In Vitro Inflammatory Integration Host Factors Intestines Investigation Laboratories Liquid substance Liver Lymphoid Lymphoid Tissue Metabolism Mus Nitrogen Normal Statistical Distribution Online Systems Organ Outcome Pathology Performance Pharmacologic Substance Physiological Preparation Property Research Resources Risk Science Services Silicates Silver Simulate Software Tools Solutions Source Spleen Swab Testing Time Tissues Toxicology Variant absorption base cost data management design drinking water gastrointestinal epithelium immunoregulation in vivo microbial nanoGold nanomaterials nanosilica nanosilver particle programs repository research study sex skills tissue resource

项目摘要

RESEARCH PLAN A. SPECIFIC AIMS. The intent of project 2 is to generate physiologically and pathobiologically relevant data via the exposure of a model organism, specifically the mouse, to nanomaterials containing silver, gold, or silicate. This basic information is fundamental to the development of risk analyses for these nanomaterials, as will be developed in Project 3. Additionally, it will provide raw materials and benchmarks of physiologic relevance for the materials science and in vitro mechanistic data generated in Project 1 and the Scientific Core. Variations in nanomaterial mass ratios and dose as well as host and environmental factors, specifically sex and gut microbial status, will be evaluated. The Scientific Aims and Functions will be achieved using polydisperse nanoAg and nanoAu with a mean diameter <100 nm obtained from commercial ('real world) sources and well characterized amorphous SiO{2} spheres from Project 1 (15, 80 and 100 nm mean diameter) mixed to give a simulated normal distribution with respect to particle number. A subset of mice will be administered the antibiotic cefoperazone (0.5 mg/ml) in drinking water for a portion of the experiment as it has been demonstrated to alter the number and composition of intestinal microbiota in humans [1, 2] and mice [3,4]. This experimental approach will be used to test the hypothesis that engineered nanomaterials alter the composition of enteric microflora and compromise the 'tone' of the epithelial barrier in the gut (collaboration between Projects 1&2). It is further hypothesized that antibiotic-induced alterations in microfloral composition and number will increase absorption of engineered nanomaterials and induce a pro-inflammatory state in the gut epithelium associated lymphoid tissues, liver and spleen. These hypotheses will be addressed by the following specific aims: Specific aim 1: Determine pharmacokinetic profiles as a function of dose and time for all three materials in a normal and a microbiotically altered (antibiotic treated) state (coordinated with Project 1) using well-characterized polydisperse preparations (Scientific Core) Specific aim 2: Determine tissue distributions as a function of dose and time for all three materials detailed in Aim 1 in a normal and a microbially altered state Specific aim 3: Determine the toxicologic pathology profile for all three materials in a normal and a microbiotically altered state Specific aim 4: Determine the immunologic profile for all three materials in the gut, blood and major lymphoid organs in the normal and microbiotically altered state

研究计划