Pathophysiology, staging and therapy of severe sepsis in baboon models.
Pathophysiology, staging and therapy of severe sepsis in baboon models.
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DOI：
10.1111/j.1582-4934.2011.01454.x
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发表时间：
2012-04
影响因子：
5.3
通讯作者：
Lupu F
中科院分区：
文献类型：
--
作者：
Taylor FB Jr;Kinasewitz GT;Lupu F
我们回顾了我们分别模拟严重脓毒症的休克/弥漫性血管内凝血(DIC)和器官衰竭变体的大肠埃希氏菌脓毒症的狒狒模型，并分析了每种模型独特的病理生理过程。严重脓毒症的多阶段、多因素特征是由于最初的侮辱而形成的，根据其强度，它激活血管内间隔的组成部分，导致压倒性休克/DIC；或启动一系列涉及血管内和外(组织)间隔的事件，导致器官衰竭。在后一种情况下，这种紊乱经历了两个阶段：由大肠杆菌引发的最初炎症/凝固性血管内阶段，随后是血管外第二阶段，涉及每个器官特有的、由缺血/再灌注(氧化应激和组蛋白释放)触发的成分。尽管涉及到大量重叠的细胞和分子成分，但正是这些成分发挥作用的背景决定了休克/DIC或器官衰竭是主导因素。例如，在第一种情况下，凝血酶放大了炎症和血栓反应，而在第二种情况下，补体激活产物放大了类似的反应。我们发现，凝血酶和补体放大通路的减弱不是阻断特定的介质，而是可以有效地逆转分别由LD100和LD50大肠杆菌严重脓毒症模型所表现出的休克/DIC和器官衰竭。这些概念的翻译，以成功干预在各自的狒狒模型的大肠杆菌败血症，并应用于他们的临床同行被描述。
We review our baboon models of Escherichia coli sepsis that mimic, respectively, the shock/disseminated intravascular coagulation (DIC) and organ failure variants of severe sepsis, and analyse the pathophysiologic processes that are unique to each. The multi-stage, multi-factorial characteristics of severe sepsis develop as a result of the initial insult, which – depending on its intensity – activates components of the intravascular compartment leading to overwhelming shock/DIC; or initiates a sequence of events involving both the intra- and extravascular (tissues) compartments that lead to organ failure. In the latter case, the disorder passes through two stages: an initial inflammatory/coagulopathic intravascular first stage triggered by E. coli, followed by an extravascular second stage, involving components unique to each organ and triggered by ischemia/reperfusion (oxidative stress and histone release). Although a myriad of overlapping cellular and molecular components are involved, it is the context in which these components are brought into play that determine whether shock/DIC or organ failure predominate. For example, inflammatory and thrombotic responses amplified by thrombin in the first case whereas similar responses are amplified by complement activation products in the second. Rather than blocking specific mediators, we found that attenuation of the thrombin and complement amplification pathways can effectively reverse the shock/DIC and organ failure exhibited by the LD100 and LD50 E. coli models of severe sepsis, respectively. Translation of these concepts to successful intervention in the respective baboon models of E. coli sepsis and the application to their clinical counterparts is described.
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组蛋白的杀菌作用。
影响因子：
15.3
作者：
HIRSCH, J G
通讯作者：
HIRSCH, J G
影响因子：
5.5
作者：
Brekke, Ole-Lars;Christiansen, Dorte;Mollnes, Tom E.
通讯作者：
Mollnes, Tom E.
影响因子：
3.6
作者：
COALSON, JJ;KUEHL, TJ;DELEMOS, RA
通讯作者：
DELEMOS, RA
DOI：
10.1007/978-0-387-78952-1_18
发表时间：
2008-01-01
期刊：
CURRENT TOPICS IN COMPLEMENT II
影响因子：
--
作者：
Mollnes, Tom Eirik;Christiansen, Dorte;Espevik, Terje
通讯作者：
Espevik, Terje
影响因子：
5.3
作者：
Harboe M;Mollnes TE
通讯作者：
Mollnes TE