Mesenteric Lymph Linking Gut & Distant Organ Injury

连接肠道的肠系膜淋巴

基本信息

项目摘要

Trauma is the leading cause of death in people under the age of 40 and MODS is the leading cause of death in intensive care units. Consequently, understanding the mechanisms by which trauma-hemorrhagic shock (T/HS) leads to MODS is of major health importance in this country. One of the major hypotheses being studied to explain the development of sepsis and MODS after trauma is the gut hypothesis of MODS. Additionally, there is recent experimental and clinical information that the response to injury and sepsis may differ between males and females. Thus, the overall global hypothesis of this grant is that trauma hemorrhagic (T/HS) shock-induced early distant organ injury and cellular dysfunction is secondary to gut injury and is primarily mediated by factors exiting the gut via the mesenteric lymphatics. Our secondary major hypothesis is that gender and sex hormones modulate gut and hence distant organ and cellular dysfunction after T/HS. These hypotheses are supported by our preliminary studies indicating that T/HSinduced lung injury and endothelial cell activation/dysfunction (Project by Deitch), neutrophil activation (Project by Hauser), red blood cell dysfunction (Project by MachiedoI) and bone marrow failure (Project by Kaiser) in male rats are mediated primarily by factors exiting the gut in the mesenteric lymph. Additionally, our studies show that proestrus female rats are resistant to these T/HS-induced injuries. Based on these results showing that female rats are more resistant to T/HS than male rats, the effects of gender and sex hormone modulation on cellular and organ dysfunction will be investigated. In all of the Projects, the mechanisms by which T/HS leads to these changes will be studied. Since T/HS-induced gut injury appears to be the initiating injury that induces this cascade of events, both Project by Deitch and Project by Feinman, will focus on determining the mechanisms by which T/HS leads to gut injury. Additionally, focused human studies in trauma patients will be carried out investigating trauma-induced neutrophil activation (Project by Hauser) and RBC dysfunction (Project by Machiedo). In summary, these projects will provide insight into the early mechanisms by which T/HS predisposes to MODS and will clarify the roles of gender and sex hormones as modulators of this response. The Administrative Core will serve to coordinate the activities of the various projects as well as be an information nexus, while the Animal Models Core will ensure consistency of the models being used and facilitate integration of the results obtained as well as reduce the costs of the overall proposal. The Human Core will serve to facilitate translational studies as well as aid in correlating the results of the human and animal studies. Lastly, Project by Kaiser focusing on factor isolation has been included to answer the question of what are the factors present in T/HS mesenteric lymph that are causing these changes in neutrophil, RBC and bone marrow function.
外伤是 40 岁以下人群死亡的主要原因,MODS 是重症监护病房中死亡的主要原因。因此,了解创伤失血性休克 (T/HS) 导致 MODS 的机制对于该国的健康具有重要意义。用于解释创伤后脓毒症和 MODS 发展的主要研究假设之一是 MODS 的肠道假说。 此外,最近的实验和临床信息表明,男性和女性对损伤和败血症的反应可能不同。因此,本次资助的总体假设是,创伤出血(T/HS)休克引起的早期远端器官损伤和细胞功能障碍继发于肠道损伤,并且主要由通过肠系膜淋巴管排出肠道的因素介导。我们的第二个主要假设是性别和性激素调节肠道,从而调节 T/HS 后的远端器官和细胞功能障碍。这些假设得到了我们初步研究的支持,表明 T/HS 诱导的肺损伤和内皮细胞激活/功能障碍(Deitch 项目)、中性粒细胞激活(Hauser 项目)、红细胞功能障碍(MachiedoI 项目)和骨髓衰竭(Project by Deitch)由 Kaiser 开发)在雄性大鼠中主要由肠系膜淋巴中离开肠道的因子介导。此外,我们的研究表明,发情前期的雌性大鼠对这些 T/HS 引起的损伤具有抵抗力。基于这些结果表明雌性大鼠比雄性大鼠对 T/HS 具有更强的抵抗力,因此将研究性别和性激素调节对细胞和器官功能障碍的影响。在所有项目中,将研究 T/HS 导致这些变化的机制。由于 T/HS 诱导的肠道损伤似乎是引发这一级联事件的起始损伤,因此 Deitch 的项目和 Feinman 的项目都将重点确定 T/HS 导致肠道损伤的机制。 此外,还将对创伤患者进行重点人体研究,调查创伤引起的中性粒细胞激活(Hauser 项目)和红细胞功能障碍(Machiedo 项目)。总之,这些项目将深入了解 T/HS 诱发 MODS 的早期机制,并将阐明性别和性激素作为这种反应调节剂的作用。行政核心将协调各个项目的活动并成为信息纽带,而动物模型核心将确保所使用模型的一致性,促进所获得结果的整合,并降低总体成本提议。人类核心将有助于促进转化研究,并帮助关联人类和动物研究的结果。最后,Kaiser 的项目重点关注因素分离,以回答 T/HS 肠系膜淋巴中存在哪些因素导致中性粒细胞、红细胞和骨髓功能发生这些变化的问题。

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Recombinant factor XIII diminishes multiple organ dysfunction in rats caused by gut ischemia-reperfusion injury.
重组因子 XIII 可减轻大鼠肠道缺血再灌注损伤引起的多器官功能障碍。
  • DOI:
    10.1097/shk.0b013e31818bbe21
  • 发表时间:
    2009
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Zaets,SergeyB;Xu,Da-Zhong;Lu,Qi;Feketova,Eleonora;Berezina,TamaraL;Gruda,Maryann;Malinina,IngaV;Deitch,EdwinA;Olsen,EvaHN
  • 通讯作者:
    Olsen,EvaHN
Elimination of C5aR prevents intestinal mucosal damage and attenuates neutrophil infiltration in local and remote organs.
  • DOI:
    10.1097/shk.0b013e318188b3cc
  • 发表时间:
    2009-05
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Xu DZ;Zaets SB;Chen R;Lu Q;Rajan H;Yang X;Zhang J;Feketova E;Bogdan N;Deitch EA;Cao Y
  • 通讯作者:
    Cao Y
Gender differences in glucose variability after severe trauma.
严重创伤后血糖变异性存在性别差异。
  • DOI:
  • 发表时间:
    2010
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Mohr,AliciaM;Lavery,RobertF;Sifri,ZiadC;Anjaria,DevashishJ;Koernig,Robert;Deitch,EdwinA;Livingston,DavidH
  • 通讯作者:
    Livingston,DavidH
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EDWIN A DEITCH其他文献

EDWIN A DEITCH的其他文献

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{{ truncateString('EDWIN A DEITCH', 18)}}的其他基金

THE ROLE OF GENDER ON GUT AND GUT-INDUCED LUNG INJURY
性别对肠道和肠道引起的肺损伤的作用
  • 批准号:
    7074169
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
Mesenteric Lymph Linking Gut & Distant Organ Injury
连接肠道的肠系膜淋巴
  • 批准号:
    7250850
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
Mesenteric Lymph Linking Gut & Distant Organ Injury
连接肠道的肠系膜淋巴
  • 批准号:
    7687551
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
Mesenteric Lymph Linking Gut & Distant Organ Injury
连接肠道的肠系膜淋巴
  • 批准号:
    7073782
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
CORE--ADMINISTRATIVE AND STATISTICS
核心——行政和统计
  • 批准号:
    7074166
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
Mesenteric Lymph Linking Gut & Distant Organ Injury
连接肠道的肠系膜淋巴
  • 批准号:
    7495413
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
Mesenteric Lymph Linking Gut & Distant Organ Injury
连接肠道的肠系膜淋巴
  • 批准号:
    7491780
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
Training in Trauma and Surgical Critical Care Research
创伤和外科重症监护研究培训
  • 批准号:
    8287542
  • 财政年份:
    2004
  • 资助金额:
    $ 160.97万
  • 项目类别:
Training in Trauma and Critical Care Research
创伤和重症监护研究培训
  • 批准号:
    7458798
  • 财政年份:
    2004
  • 资助金额:
    $ 160.97万
  • 项目类别:
Training in Trauma and Surgical Critical Care Research
创伤和外科重症监护研究培训
  • 批准号:
    8496066
  • 财政年份:
    2004
  • 资助金额:
    $ 160.97万
  • 项目类别:

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相似海外基金

Mesenteric Lymph Linking Gut & Distant Organ Injury
连接肠道的肠系膜淋巴
  • 批准号:
    7250850
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
Mesenteric Lymph Linking Gut & Distant Organ Injury
连接肠道的肠系膜淋巴
  • 批准号:
    7687551
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
Mesenteric Lymph Linking Gut & Distant Organ Injury
连接肠道的肠系膜淋巴
  • 批准号:
    7073782
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
Mesenteric Lymph Linking Gut & Distant Organ Injury
连接肠道的肠系膜淋巴
  • 批准号:
    7495413
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
  • 项目类别:
Mesenteric Lymph Linking Gut & Distant Organ Injury
连接肠道的肠系膜淋巴
  • 批准号:
    7491780
  • 财政年份:
    2006
  • 资助金额:
    $ 160.97万
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