Treating sepsis with PAF Acetylhydrolase
用 PAF 乙酰水解酶治疗败血症
基本信息
- 批准号:6335496
- 负责人:
- 金额:$ 4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-07-01 至 2004-06-30
- 项目状态:已结题
- 来源:
- 关键词:Brazil Neisseria meningitidis acute disease /disorder adult respiratory distress syndrome bacterial disease bacterial meningitis carboxylic ester hydrolases clinical research clinical trials cooperative study cytokine disease /disorder model enzyme activity enzyme mechanism gene targeting genetically modified animals human subject human therapy evaluation laboratory mouse lung injury microorganism disease chemotherapy nonhuman therapy evaluation phospholipids placebos recombinant proteins
项目摘要
In this application we propose to test if removal of PAF and related
phospholipids reduces the mortality associated with certain forms of sepsis. To
test this hypothesis, we will examine the effect of administration of
recombinant PAF acetylhydrolase, the enzyme that inactivates PAF and related
phospholipids, to animals undergoing sepsis. We will use survival as the
endpoint but will also characterize the response to enzyme administration by
comparing cytokine levels in animals treated with placebo or with the
recombinant protein. We will utilize two experimental models of sepsis: cecal
ligation and puncture and sepsis induced by injection of Neisseria
meningitidis. As a clinical corollary, we will determine the levels of PAF
acetylhydrolase activity and cytokine levels in the plasma of patients
undergoing sepsis and meningococcemia. An important goal of these studies, in
addition to testing the potential of PAF acetylhydrolase as a therapeutic
agent, is to identify patient groups that are likely to benefit the most from
PAF acetylhydrolase administration. Recent clinical studies have failed to
demonstrate that anti-inflammatory or immunomodulatory agents have beneficial
effects in the treatment of sepsis. A possible explanation for this observation
is that the patient population studied included subjects in whom a variety of
different mechanisms resulted in sepsis. This may have precluded the ability of
the agent(s) tested to show a beneficial effect in a limited group of patients
because such effects would be lost in the analysis of the entire patient group.
Our hypothesis is that the definition of sub-populations with similar
etiologies will be a key factor in our understanding of sepsis. This approach
will facilitate identification of markers to characterize the evolution and
outcome of the disease as well as identify novel therapies. For example,
patients suffering from meningococcemia-related sepsis can be identified as a
homogeneous sub-population of septic patients. The studies proposed here may
facilitate the molecular identification and treatment of populations that can
significantly benefit from PAF acetylhydrolase administration. These studies
will be carried out primarily in Brazil, as an extension of NIH SCOR grant P50
HL50153 (Project 5). They constitute an ideal complement to the studies
currently being performed by Drs. Prescott and Stafforini, who are the
Principal Investigator and Project Director of Project 5 of the SCOR in Acute
Lung Injury, respectively.
在此应用程序中,我们建议测试是否移除PAF和相关
磷脂可降低某些形式的脓毒症的死亡率。至
检验这一假设,我们将检验给药的效果
重组PAF乙酰水解酶,使PAF及其相关酶失活
磷脂,对正在经历败血症的动物。我们将把生存作为
终点,但也将表征对酶注射的反应,通过
比较服用安慰剂和安慰剂的动物的细胞因子水平
重组蛋白。我们将利用两种脓毒症的实验模型:盲肠
注射奈瑟氏菌所致的结扎穿刺术和脓毒症
脑膜炎。作为临床推论,我们将测定PAF水平
患者血浆中乙酰水解酶活性和细胞因子水平的变化
正在经历败血症和脑膜炎双球菌血症。这些研究的一个重要目标是
除了测试PAF乙酰水解酶作为治疗药物的潜力
代理,是确定可能受益最大的患者群体
PAF乙酰水解酶给药。最近的临床研究未能达到
证明抗炎或免疫调节剂有好处
在脓毒症治疗中的作用。对这一观察结果有一种可能的解释
被研究的患者群体包括各种不同类型的
不同的机制导致败血症。这可能已经排除了
该制剂(S)经测试在有限的一组患者中显示出有益的效果
因为在对整个患者群体的分析中,这种影响将会消失。
我们的假设是,具有相似特征的亚种群的定义
病因将是我们了解脓毒症的关键因素。这种方法
将有助于识别标记以表征进化和
评估疾病的转归,以及确定新的治疗方法。例如,
患有脑膜炎球菌血症相关败血症的患者可被确定为
脓毒症患者的同质性亚群。这里提出的研究可能
促进分子鉴定和治疗能够
显著受益于PAF乙酰水解酶的应用。这些研究
将主要在巴西进行,作为NIH SCOR赠款的延期P50
HL50153(项目5)。它们构成了对研究的理想补充
目前由普雷斯科特博士和斯塔福里尼博士表演,他们是
SCOR项目5的首席调查员兼项目主任
肺损伤。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Stephen M Prescott其他文献
Inhibition of Platelet-activating Factor Acetylhydrolase Activity by Oxidants. † 1541
氧化剂对血小板活化因子乙酰水解酶活性的抑制作用。†1541
- DOI:
10.1203/00006450-199704001-01560 - 发表时间:
1997-04-01 - 期刊:
- 影响因子:3.100
- 作者:
Amy N MacRitchie;Kun Qu;Diana M Stafforini;Thomas M McIntyre;Guy A Zimmerman;Stephen M Prescott - 通讯作者:
Stephen M Prescott
Fish oil fix
鱼油疗法
- DOI:
10.1038/nm0605-596 - 发表时间:
2005-06-01 - 期刊:
- 影响因子:50.000
- 作者:
Stephen M Prescott;William F Stenson - 通讯作者:
William F Stenson
Stephen M Prescott的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Stephen M Prescott', 18)}}的其他基金
Oklahoma Medical Research Foundation Clinical Research Construction
俄克拉荷马州医学研究基金会临床研究建设
- 批准号:
7898373 - 财政年份:2010
- 资助金额:
$ 4万 - 项目类别:
相似海外基金
Molecular mechanisms underlying glial inflammatory responses to Neisseria meningitidis: A pilot study
神经胶质细胞对脑膜炎奈瑟菌炎症反应的分子机制:一项初步研究
- 批准号:
10452116 - 财政年份:2022
- 资助金额:
$ 4万 - 项目类别:
Molecular mechanisms underlying glial inflammatory responses to Neisseria meningitidis: A pilot study
神经胶质细胞对脑膜炎奈瑟菌炎症反应的分子机制:一项初步研究
- 批准号:
10551245 - 财政年份:2022
- 资助金额:
$ 4万 - 项目类别:
Identification of bactericidal antibody specificities for the development of novel broad-coverage vaccine candidates against Neisseria meningitidis
鉴定杀菌抗体特异性,用于开发针对脑膜炎奈瑟菌的新型广泛覆盖候选疫苗
- 批准号:
10404598 - 财政年份:2021
- 资助金额:
$ 4万 - 项目类别:
Acquisition of gonococcal denitrification apparatus in the Neisseria meningitidis urethritis clade
脑膜炎奈瑟菌尿道炎分支中淋菌反硝化装置的获得
- 批准号:
10317302 - 财政年份:2021
- 资助金额:
$ 4万 - 项目类别:
Acquisition of gonococcal denitrification apparatus in the Neisseria meningitidis urethritis clade
脑膜炎奈瑟菌尿道炎分支中淋菌反硝化装置的获得
- 批准号:
10448441 - 财政年份:2021
- 资助金额:
$ 4万 - 项目类别:
Identification of bactericidal antibody specificities for the development of novel broad-coverage vaccine candidates against Neisseria meningitidis
鉴定杀菌抗体特异性,用于开发针对脑膜炎奈瑟菌的新型广泛覆盖候选疫苗
- 批准号:
10256250 - 财政年份:2021
- 资助金额:
$ 4万 - 项目类别:
Defining the link between viral co-infection and the invasive potential of Neisseria meningitidis
确定病毒合并感染与脑膜炎奈瑟菌侵袭潜力之间的联系
- 批准号:
449574 - 财政年份:2020
- 资助金额:
$ 4万 - 项目类别:
Studentship Programs
Antimicrobial susceptibility and penicillin resistance mechanism in the Japanese clinical isolates of Neisseria meningitidis
日本临床分离脑膜炎奈瑟菌的耐药性及青霉素耐药机制
- 批准号:
20K08818 - 财政年份:2020
- 资助金额:
$ 4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Revealing processes that confer immunity against nasal colonization by Neisseria meningitidis
揭示赋予脑膜炎奈瑟菌鼻定植免疫力的过程
- 批准号:
408154 - 财政年份:2018
- 资助金额:
$ 4万 - 项目类别:
Studentship Programs
The CRISPR/Cas system in Neisseria meningitidis and its potential role in host cell adhesion
脑膜炎奈瑟菌中的CRISPR/Cas系统及其在宿主细胞粘附中的潜在作用
- 批准号:
405974664 - 财政年份:2018
- 资助金额:
$ 4万 - 项目类别:
Priority Programmes














{{item.name}}会员




