INTESTINAL PERFUSION AND PERMEABILITY IN SEPSIS
脓毒症的肠道灌注和渗透性
基本信息
- 批准号:2684840
- 负责人:
- 金额:$ 29.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1987
- 资助国家:美国
- 起止时间:1987-04-01 至 2000-03-31
- 项目状态:已结题
- 来源:
- 关键词:adenylate kinase allopurinol antioxidants bacterial disease blood toxicology cytoskeleton endotoxins free radical scavengers gastrointestinal circulation gastrointestinal epithelium gastrointestinal toxin absorption intercellular connection intestinal mucosa ischemia lipopolysaccharides membrane permeability microelectrodes myeloperoxidase oxygen tension septic shock swine
项目摘要
DESCRIPTION: (Adapted from the applicant's abstract) This competing
renewal application is based on the hypothesis that gut epithelial
barrier function is deranged by cellular acidosis. In the currently
funded research, the investigator has shown that ileal mucosal acidosis
in pigs increases mucosal permeability in vivo, and that exposure of
mucosal cell (CaCo-2BBe) monolayers to acid also induce an increase in
epithelial permeability in vitro. The investigator's studies have also
shown that acidosis promotes lipid peroxidation, increases intracellular
Fe2+, and partly depletes cellular ATP in the CaCo-2BBe enterocytes.
These studies have demonstrated also that inhibition of calpain and
phospholipases ameliorated acid induced mucosal hyperpermeability.
These studies collectively support the concept that intracellular
calcium related derangements may be important in the pathogenesis of acid
induced mucosal barrier dysfunction. The present proposal will extend
the studies of CaCo-2BBe cells and monocytes by: 1) measuring
intracellular [H+], 2) assessing the effect of acidosis and ATP
depletion on epithelial permeability to water soluble macromolecule as
well as to particulate matter such as LPS and E.coli bacteria. In
addition the proposal will focus on cytoskeletal integrity and its
relationship to acidosis induced mucosal cell permeability dysfunction
in CaCo-2BBe monolayers. Studies will evaluate also the effect of
acidosis or moderate ATP depletion in the enterocytes on [Ca2+]i, and
the effects of A23187, BAPTA, and various modifiers of phospholipases
calpains and PKC on the acid and/or low ATP level induced mucosal
permeability dysfunction. all of the aforementioned studies are to be
carrier in the CaCo-2BBe cell line in vitro. Finally, experiments will
ascertain the various determinants of ileal mucosal permeability
dysfunction in the in vivo studies in a rat model of hemorrhagic injury.
These studies will employ in vivo methodology to determine both
translocation of LPS and permeability of macromolecules across the ileal
epithelium.
描述:(改编自申请人的摘要)这一竞争
更新申请是基于这样的假设,即肠上皮细胞
屏障功能被细胞酸中毒破坏。 在当前
资助的研究,研究人员已经表明,回肠粘膜酸中毒,
在猪体内增加粘膜渗透性,
粘膜细胞(CaCo-2BBe)单层对酸的反应也诱导了
体外上皮通透性。 研究人员的研究还表明,
表明酸中毒促进脂质过氧化,增加细胞内
Fe ~(2+),并部分消耗CaCo-2BBe肠细胞中的细胞ATP。
这些研究还表明,抑制钙蛋白酶和
磷脂酶可改善酸诱导的粘膜通透性增高。
这些研究共同支持细胞内
钙相关紊乱可能是重要的发病机制酸
引起粘膜屏障功能障碍。 本提案将扩大
CaCo-2BBe细胞和单核细胞的研究:1)测量
细胞内[H+],2)评估酸中毒和ATP的影响
消耗上皮细胞对水溶性大分子的渗透性,
以及颗粒物质如LPS和大肠杆菌。 在
此外,该提案将侧重于细胞骨架的完整性及其
与酸中毒诱导的粘膜细胞通透性功能障碍的关系
在CaCo-2BBe单分子膜中。 研究还将评估
肠细胞中[Ca 2 +]i的酸中毒或中度ATP耗竭,以及
A23187、BAPTA和各种磷脂酶修饰剂的作用
钙蛋白酶和蛋白激酶C对酸性和/或低ATP水平诱导的粘膜炎症反应的影响
通透性功能障碍 所有上述研究都将
CaCo-2BBe细胞系的体外培养。 最后,实验将
确定回肠粘膜通透性的各种决定因素
在大鼠出血性损伤模型的体内研究中,
这些研究将采用体内方法来确定
LPS的移位和大分子穿过回肠的渗透性
上皮
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Mitchell P. Fink其他文献
Effects of nonsteroidal anti-inflammatory drugs on renal function in septic dogs.
非甾体抗炎药对脓毒症犬肾功能的影响。
- DOI:
10.1016/0022-4804(84)90135-5 - 发表时间:
1984 - 期刊:
- 影响因子:0
- 作者:
Mitchell P. Fink;Thomas J. MacVittie;Larry C. Casey - 通讯作者:
Larry C. Casey
Postoperative complications in patients with disabling psychiatric illnesses or intellectual handicaps. A case-controlled, retrospective analysis.
患有致残性精神疾病或智力障碍的患者的术后并发症。
- DOI:
10.1001/archsurg.1990.01410230030005 - 发表时间:
1990 - 期刊:
- 影响因子:0
- 作者:
B. Cutler;Mitchell P. Fink - 通讯作者:
Mitchell P. Fink
Biology of heterotrimeric G-protein signaling.
异源三聚体 G 蛋白信号传导生物学。
- DOI:
- 发表时间:
2000 - 期刊:
- 影响因子:8.8
- 作者:
R. Forse;John M. Luce;Michael B. Yaffe;Mitchell P. Fink - 通讯作者:
Mitchell P. Fink
Hemorrhagic Ascites: An Unusual Presentation of Primary Splenic Lymphoma
- DOI:
10.1016/s0016-5085(82)80346-6 - 发表时间:
1982-08-01 - 期刊:
- 影响因子:
- 作者:
Joseph F. Hacker;Joel E. Richter;Robert S. Pyatt;Mitchell P. Fink - 通讯作者:
Mitchell P. Fink
CRISIS IN CRITICAL CARE The Demand for Critical Care Services is Increasing Critical care
重症监护危机 对重症监护服务的需求正在增加 重症监护
- DOI:
- 发表时间:
2005 - 期刊:
- 影响因子:0
- 作者:
David T. Huang;T. Osborn;K. Gunnerson;Scott R. Gunn;Stephen Trzeciak;Edward Kimball;Mitchell P. Fink;De Angus;R. Dellinger;Emanuel P. Rivers - 通讯作者:
Emanuel P. Rivers
Mitchell P. Fink的其他文献
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{{ truncateString('Mitchell P. Fink', 18)}}的其他基金
MOLECULAR BASIS FOR EPITHELIAL BARRIER DYSFUNCTION/PROJECT 2
上皮屏障功能障碍的分子基础/项目 2
- 批准号:
6829217 - 财政年份:2004
- 资助金额:
$ 29.47万 - 项目类别:
Ethyl Pyruvate: A Novel Treatment for Sepsis
丙酮酸乙酯:脓毒症的新型治疗方法
- 批准号:
6765286 - 财政年份:2003
- 资助金额:
$ 29.47万 - 项目类别:
Ethyl Pyruvate: A Novel Treatment for Sepsis
丙酮酸乙酯:脓毒症的新型治疗方法
- 批准号:
6911508 - 财政年份:2003
- 资助金额:
$ 29.47万 - 项目类别:
Ethyl Pyruvate: A Novel Treatment for Sepsis
丙酮酸乙酯:脓毒症的新型治疗方法
- 批准号:
6669337 - 财政年份:2003
- 资助金额:
$ 29.47万 - 项目类别:
COMPLEMENT-DEPENDENT PROSTAGLANDIN SYNTHESIS IN SEPSIS
脓毒症中补体依赖性前列腺素合成
- 批准号:
3466035 - 财政年份:1987
- 资助金额:
$ 29.47万 - 项目类别:
COMPLEMENT-DEPENDENT PROSTAGLANDIN SYNTHESIS IN SEPSIS
脓毒症中补体依赖性前列腺素合成
- 批准号:
3466038 - 财政年份:1987
- 资助金额:
$ 29.47万 - 项目类别:
COMPLEMENT-DEPENDENT PROSTAGLANDIN SYNTHESIS IN SEPSIS
脓毒症中补体依赖性前列腺素合成
- 批准号:
3466034 - 财政年份:1987
- 资助金额:
$ 29.47万 - 项目类别:
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