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: 7919160
• 负责人: JENNIFER F FRIEDMAN
• 金额: $ 4.92万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-12 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7919160
• 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; Iron; Iron deficiency anemia; Leishmania; Link; Malaria; Mediating; Modeling; Morbidity - disease rate; Mothers; Nature; Outcome; Parasitic Diseases; Pathology; Peptides; Philippines; Placenta; Praziquantel; Pregnancy; Pregnancy Outcome; Pregnant Women; Principal Investigator; Randomized Controlled Trials; Research Infrastructure; Research Personnel; Rheumatoid Arthritis; Sampling; Schistosoma japonicum; Schistosomiasis; Side; Syncytiotrophoblast; Systemic Lupus Erythematosus; Th2 Cells; Tissues; Transferrin Receptor; Tuberculosis; United States National Institutes of Health; Weight; Work; absorption; cytokine; hepcidin; iron metabolism; mortality; novel; pregnant; premature; 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）：该K02的广泛目标是扩展我们对japonicum S. japonicum感染中介导不良出生结果的基本机制的理解，并扩展了既定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品，用于怀孕期间的japonicum链球菌治疗。 U01研究刚刚开始了五年的第二年，并将在2007年6月中开始招募。这项工作的具体目标是研究如何治疗Japonicum S. japonicum的治疗方法如何改变胎盘铁的代谢，修饰placenta的细胞因子微环境，以及这是如何改变胎盘健康的定义，定义了滋养细胞细胞凋亡的定义。这项工作本质上是高度协作的，可以检查U01研究未解决的Japonicum链球菌相关的妊娠发病率。这将使主要研究人员能够探索新颖的询问途径，而不是她目前的主要技能。 Japonicum S. japonicum提供了一个出色的模型，用于了解系统性炎症（包括炎症的贫血，铁代谢的随之改变）会影响妊娠结局。由于它很容易治疗，并且显示出在治疗的几周内会消失的全身性炎症，因此该疾病提供了一种出色的模型，可以在其中研究怀孕期间全身炎症的影响。因此，这项工作可以推广到许多感染性和非感染性疾病的妊娠疾病，这些疾病产生了繁殖的促炎性免疫反应，包括HIV，结核病，全身性红斑狼疮等。