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

描述（由申请人提供）：本K02的广泛目标是扩大我们对S.日本血吸虫感染，并扩大了既定研究者的科学专业知识领域。拟议的工作将利用NIH资助的吡喹酮治疗沙门氏菌的随机对照试验（U01AI066050）收集的基础设施和样本。日本在怀孕期间。U01研究刚刚开始其五年中的第二年，并将于2007年6月中旬开始招募。这项工作的具体目标是研究如何治疗S。日本血吸虫改变胎盘铁代谢，改变胎盘的细胞因子微环境，以及这如何改变胎盘健康，如通过定量滋养层细胞凋亡所定义的。这项工作本质上是高度协作的，可以检查S的基本机制。U01研究未涉及日本血吸虫相关妊娠发病率。这将使主要研究者能够探索新的调查途径，而不是目前她的主要技能。S. japonicum提供了一个很好的模型来了解全身性炎症，包括炎症性贫血和伴随的铁代谢改变如何影响妊娠结局。由于它很容易治疗，并且全身性炎症在治疗的几周内就会消失，这种疾病提供了一个很好的模型来研究妊娠期间全身性炎症的影响。因此，这项工作可推广到许多感染性和非感染性妊娠疾病，这些疾病产生旺盛的促炎免疫反应，包括HIV，结核病，系统性红斑狼疮等。

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.