Mechanisms mediating adverse birth outcomes in the context of S. Japonicum infect

日本血吸虫感染情况下介导不良出生结局的机制

• 批准号: 7448156
• 负责人: JENNIFER F FRIEDMAN
• 金额: $ 10.45万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7448156
• 关键词: Address; Affect; Anemia; Anemia due to Chronic Disorder; Animal Model; Apoptosis; Area; Birth; Blood Circulation; Bone Marrow; Cells; Communicable Diseases; Data; Data Collection; Developed Countries; Developing Countries; Disease; Environment; Erythropoietin; Feces; Female of child bearing age; Fetal Growth Retardation; Funding; Goals; HIV; Health; Human; Immune response; Incidence; Individual; Infection; Inflammation; Inflammatory; Interleukin-6; Invasive; Iron; Iron deficiency anemia; Leishmania; Link; Malaria; Mediating; Modeling; Morbidity - disease rate; Mothers; Nature; Outcome; Parasitic Diseases; Pathology; Patient currently pregnant; Peptides; Philippines; Placenta; Praziquantel; Pregnancy; Pregnancy Outcome; Pregnant Women; Prematurity of fetus; Principal Investigator; Randomized Controlled Trials; Research Infrastructure; Research Personnel; Rheumatoid Arthritis; Sampling; Schistosoma japonicum; Schistosomiasis; Side; Syncytiotrophoblast; Systemic Lupus Erythematosus; Th2 Cells; Thinking; Tissues; Transferrin Receptor; Tuberculosis; United States National Institutes of Health; Week; Weight; Work; absorption; cytokine; hepcidin; human study; iron metabolism; mortality; novel; response; skills; trophoblast

DESCRIPTION (provided by applicant): The broad goals of this K02 are to expand our understanding of basic mechanisms mediating adverse birth outcomes in the context of S. japonicum infection and to extend the areas of scientific expertise of an established investigator. The proposed work will leverage the infrastructure and samples collected by an NIH funded randomized controlled trial (U01AI066050) of praziquantel treatment for S. japonicum during pregnancy. The U01 study just started its second of five years and will begin recruitment in mid June of 2007. The specific goals of this work are to examine how treatment for S. japonicum alters placental iron metabolism, modifies the cytokine micro-environment of the placenta, and how this alters placental health as defined by quantification of trophoblast apoptosis. This work is highly collaborative in nature, allowing examination of basic mechanism of S. japonicum related pregnancy morbidity not addressed by the U01 study. This will allow the principal investigator to explore novel avenues of inquiry, not currently her primary skill set. S. japonicum offers an outstanding model for understanding how systemic inflammation, including anemia of inflammation with attendant alterations in iron metabolism affects pregnancy outcomes. Due to the fact that it is easily treated and systemic inflammation is shown to dissipate within a few weeks of therapy, this disease provides an excellent model in which to study the effects of systemic inflammation during pregnancy. Thus, this work is generalizable to a host of infectious and non-infectious diseases of pregnancy that generate an exuberant pro-inflammatory immune response including HIV, tuberculosis, systemic lupus erythematosus, and many others.

描述（由申请人提供）：本 K02 的广泛目标是扩大我们对日本血吸虫感染背景下介导不良分娩结果的基本机制的理解，并扩展现有研究者的科学专业知识领域。拟议的工作将利用 NIH 资助的随机对照试验 (U01AI066050) 收集的基础设施和样本，该试验对怀孕期间的日本血吸虫进行吡喹酮治疗。 U01 研究刚刚开始五年中的第二个研究，将于 2007 年 6 月中旬开始招募。这项工作的具体目标是研究日本血吸虫治疗如何改变胎盘铁代谢、改变胎盘的细胞因子微环境，以及这如何改变胎盘健康（通过滋养层细胞凋亡的量化来定义）。这项工作本质上是高度协作的，可以检查 U01 研究未解决的与日本血吸虫相关的妊娠发病率的基本机制。这将使首席研究员能够探索新颖的调查途径，而不是目前她的主要技能。日本血吸虫为了解全身性炎症（包括炎症性贫血以及随之而来的铁代谢改变）如何影响妊娠结局提供了一个出色的模型。由于该疾病易于治疗，并且全身炎症在治疗几周内就会消散，因此该疾病提供了一个极好的模型来研究妊娠期间全身炎症的影响。因此，这项工作可推广到一系列产生旺盛促炎性免疫反应的妊娠期传染性和非传染性疾病，包括艾滋病毒、结核病、系统性红斑狼疮等。