C60, MWCNTs and the Influence on Cardiovascular, Reproductive, and Developmental

C60、多壁碳纳米管及其对心血管、生殖和发育的影响

基本信息

  • 批准号:
    8464701
  • 负责人:
  • 金额:
    $ 118.99万
  • 依托单位:
  • 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:
    2010-09-27 至 2015-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The proposed U19 Center will foster collaboration between RTI researchers who have developed capabilities to synthesize and characterize unlabeled and uniformly carbon-14 labeled carbon-based nanoparticles and that have investigated the fate of these materials in pregnant and lactating rodent models, with East Carolina University (ECU) researchers who have experimental programs funded by the National Institute of Environmental Health Sciences to investigate the cardiovascular and pulmonary responses of carbon nanotubes. Data developed by RTI and ECU researchers will be used by scientists at The Hamner Institutes for Health Sciences to develop physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) models for assessment of health risks. Experimental data collection with concurrent modeling will greatly enhance the power of the scientific method in that the model will sen/e as a conceptual framework to capture the knowledge and intuitions ofthe investigators in a quantitatively predictive structure. ECU's research demonstrates that pulmonary exposure to MWCNTs can exacerbate an episode of ischemic/reperfusion injury in the heart of normal healthy animals, and that the mechanism underlying this process may be driven by systemic inflammation and changes in vascular reactivity. Pregnancy and lactation may be susceptible conditions with respect to the effects of nanoparticles on the mothers and their offspring, and it is likely that changes in the vasculature can led to alterations in the blood flow to organs and contribute to how nanomaterials distribute to the organs of the mother, fetus, and neonates. Preliminary data developed by RTI demonstrate that carbon-based nanoparticles can transfer from an exposed rodent dam to the fetus and nursing pup. These data raise concerns for potential developmental effects; however, evaluation of the human relevance of these findings requires consideration ofthe physiological differences between rodents and humans. In Project 1, we propose to determine how characteristics of C60 fullerene (C60) and MWCNTs affect cellular uptake, clearance, and responses in endothelial and epithelial cells isolated from the heart, lung, and placenta. In project 2, we propose to determine the PK and absorption, distribution, metabolism, and excretion of these nanoparticles in the female rodent, pregnant rodent (and fetus), and lactating rodent (and neonate), and to determine how exposure affects the vascular reactivity ofthe heart, lung, and uterus. Further, we propose to measure markers of inflammation (cytokines), oxidative stress (8- hydroxydeoxyguanosine), and reproductive and developmental effects (hormones and phenotypic anchors).
描述(申请人提供):拟议的U19中心将促进RTI研究人员之间的合作,这些研究人员已经开发出合成和表征未标记和均匀碳-14标记的碳基纳米颗粒的能力,并研究了这些材料在怀孕和哺乳啮齿动物模型中的命运,东卡罗莱纳大学(ECU)由国家环境健康科学研究所资助的实验项目的研究人员,研究碳对心血管和肺的反应。纳米管。RTI和ECU研究人员开发的数据将由Hamner健康科学研究所的科学家用于开发基于生理学的药代动力学/药效学(PBPK/PD)模型,用于评估健康风险。实验数据收集与并行建模将大大增强科学方法的力量,因为模型将作为一个概念框架,以定量预测结构捕获调查人员的知识和直觉。ECU的研究表明,肺部暴露于多壁碳纳米管可以加剧正常健康动物心脏的缺血/再灌注损伤,并且该过程的机制可能是由全身炎症和血管反应性变化驱动的。怀孕和哺乳可能是纳米颗粒对母亲及其后代影响的易感条件,并且血管系统的变化可能会导致流向器官的血流改变,并影响纳米材料如何分布到母亲、胎儿和新生儿的器官。RTI开发的初步数据表明,碳基纳米颗粒可以从暴露的啮齿动物母体转移到胎儿和哺乳期幼犬。这些数据引起了对潜在发育影响的担忧;然而,评估这些发现的人类相关性需要考虑啮齿动物和人类之间的生理差异。在项目1中,我们建议确定C60富勒烯(C60)和多壁碳纳米管的特性如何影响从心脏,肺和胎盘分离的内皮细胞和上皮细胞的细胞摄取,清除和反应。在项目2中,我们建议确定这些纳米颗粒在雌性啮齿动物、妊娠啮齿动物(和胎儿)和哺乳啮齿动物(和新生儿)中的PK和吸收、分布、代谢和排泄,并确定暴露如何影响心脏、肺和子宫的血管反应性。此外,我们建议测量炎症(细胞因子),氧化应激(8-羟基脱氧鸟苷),生殖和发育影响(激素和表型锚)的标志物。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Harvey Joseph Clewell其他文献

Harvey Joseph Clewell的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Harvey Joseph Clewell', 18)}}的其他基金

C60, MWCNTs and the Influence on Cardiovascular, Reproductive, and Developmental
C60、多壁碳纳米管及其对心血管、生殖和发育的影响
  • 批准号:
    8016783
  • 财政年份:
    2010
  • 资助金额:
    $ 118.99万
  • 项目类别:
C60, MWCNTs and the Influence on Cardiovascular, Reproductive, and Developmental
C60、多壁碳纳米管及其对心血管、生殖和发育的影响
  • 批准号:
    8274458
  • 财政年份:
    2010
  • 资助金额:
    $ 118.99万
  • 项目类别:
C60, MWCNTs and the Influence on Cardiovascular, Reproductive, and Developmental
C60、多壁碳纳米管及其对心血管、生殖和发育的影响
  • 批准号:
    8734638
  • 财政年份:
    2010
  • 资助金额:
    $ 118.99万
  • 项目类别:
C60, MWCNTs and the Influence on Cardiovascular, Reproductive, and Developmental
C60、多壁碳纳米管及其对心血管、生殖和发育的影响
  • 批准号:
    8675235
  • 财政年份:
    2010
  • 资助金额:
    $ 118.99万
  • 项目类别:
C60, MWCNTs and the Influence on Cardiovascular, Reproductive, and Developmental
C60、多壁碳纳米管及其对心血管、生殖和发育的影响
  • 批准号:
    8150501
  • 财政年份:
    2010
  • 资助金额:
    $ 118.99万
  • 项目类别:
Project 3 Physiologically-based pharmacokinetic/pharmacodynamic modeling of C60
项目3 基于生理学的C60药代动力学/药效学建模
  • 批准号:
    8066896
  • 财政年份:
    2010
  • 资助金额:
    $ 118.99万
  • 项目类别:
Project 3 Physiologically-based pharmacokinetic/pharmacodynamic modeling of C60
项目3 基于生理学的C60药代动力学/药效学建模
  • 批准号:
    8274455
  • 财政年份:
  • 资助金额:
    $ 118.99万
  • 项目类别:

相似海外基金

6-thio-2'-deoxyguanosine in GBM: Evaluation of Pharmaco-dynamics, Effects of Prior Standard of Care and A Human Phase 0 Study
GBM 中的 6-硫代-2-脱氧鸟苷:药效学评估、先前护理标准的影响和人类 0 期研究
  • 批准号:
    10305569
  • 财政年份:
    2021
  • 资助金额:
    $ 118.99万
  • 项目类别:
6-thio-2'-deoxyguanosine in GBM: Evaluation of Pharmaco-dynamics, Effects of Prior Standard of Care and A Human Phase 0 Study
GBM 中的 6-硫代-2-脱氧鸟苷:药效学评估、先前护理标准的影响和人类 0 期研究
  • 批准号:
    10488244
  • 财政年份:
    2021
  • 资助金额:
    $ 118.99万
  • 项目类别:
6-thio-2'-deoxyguanosine: A Novel Immunogenic Telomerase-Mediated Therapy in Glioblastoma - A Duke and UTSW Collaboration
6-硫代-2-脱氧鸟苷:一种新型免疫原性端粒酶介导的胶质母细胞瘤疗法 - 杜克大学和 UTSW 合作
  • 批准号:
    10305565
  • 财政年份:
    2021
  • 资助金额:
    $ 118.99万
  • 项目类别:
6-thio-2'-deoxyguanosine in GBM: Pre-clinical Evaluation of Mechanism of action, Efficacy and Biomarker identification
GBM 中的 6-硫代-2-脱氧鸟苷:作用机制、功效和生物标志物鉴定的临床前评估
  • 批准号:
    10488242
  • 财政年份:
    2021
  • 资助金额:
    $ 118.99万
  • 项目类别:
6-thio-2'-deoxyguanosine: A Novel Immunogenic Telomerase-Mediated Therapy in Glioblastoma - A Duke and UTSW Collaboration
6-硫代-2-脱氧鸟苷:一种新型免疫原性端粒酶介导的胶质母细胞瘤疗法 - 杜克大学和 UTSW 合作
  • 批准号:
    10488237
  • 财政年份:
    2021
  • 资助金额:
    $ 118.99万
  • 项目类别:
6-thio-2'-deoxyguanosine in GBM: Pre-clinical Evaluation of Mechanism of action, Efficacy and Biomarker identification
GBM 中的 6-硫代-2-脱氧鸟苷:作用机制、功效和生物标志物鉴定的临床前评估
  • 批准号:
    10305568
  • 财政年份:
    2021
  • 资助金额:
    $ 118.99万
  • 项目类别:
RUI: Chemical Investigations into the Bioactivity of the DNA Lesion 8-Oxo-2'-deoxyguanosine
RUI:DNA 损伤 8-Oxo-2-脱氧鸟苷生物活性的化学研究
  • 批准号:
    1903855
  • 财政年份:
    2019
  • 资助金额:
    $ 118.99万
  • 项目类别:
    Standard Grant
Toxicity and Biosensing Properties of C8-Aryl-Deoxyguanosine Adducts
C8-芳基-脱氧鸟苷加合物的毒性和生物传感特性
  • 批准号:
    311600-2013
  • 财政年份:
    2017
  • 资助金额:
    $ 118.99万
  • 项目类别:
    Discovery Grants Program - Individual
Toxicity and Biosensing Properties of C8-Aryl-Deoxyguanosine Adducts
C8-芳基-脱氧鸟苷加合物的毒性和生物传感特性
  • 批准号:
    311600-2013
  • 财政年份:
    2015
  • 资助金额:
    $ 118.99万
  • 项目类别:
    Discovery Grants Program - Individual
Toxicity and Biosensing Properties of C8-Aryl-Deoxyguanosine Adducts
C8-芳基-脱氧鸟苷加合物的毒性和生物传感特性
  • 批准号:
    311600-2013
  • 财政年份:
    2014
  • 资助金额:
    $ 118.99万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了