Restoration and Function of S-Nitrosothiol in Stored Blood

储存血液中S-亚硝基硫醇的恢复和作用

基本信息

  • 批准号:
    10586343
  • 负责人:
  • 金额:
    $ 56.72万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-12-01 至 2028-01-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY The therapeutic benefit of transfusion presumes a direct correlation between blood oxygen carrying capacity and oxygen delivery. However, our preclinical and clinical studies show that stored blood loses its ability to oxygenate tissues. The sequelae that can occur after transfusion (renal injury, myocardial infarction, death) are consistent with the idea that banked blood may exacerbate rather than correct anemia-induced hypoxia. We have discovered that banked blood has markedly diminished levels of nitric oxide/S-nitrosothiol (NO/SNO) bioactivity including the S-nitrosylated form of hemoglobin (SNO-Hb), a major mediator of blood flow and peripheral oxygen delivery. This decline in SNO provides a mechanistic basis for the impaired vasodilatory activity of stored red blood cells (RBCs) and an explanation for why transfusion of even small amounts of blood may impair tissue perfusion. We have built on this novel finding by demonstrating that restoration of SNO-Hb levels (renitrosylation) corrects storage-induced deficiencies in RBC oxygen delivery and transfusion-induced organ dysfunction in multiple preclinical transfusion paradigms, and we have initiated clinical studies to assess the effects of transfusion on tissue oxygenation. We have also developed first-in-class renitrosylating agents that are already undergoing clinical testing. We are positioned to provide critically needed data on the effects of transfusion on tissue oxygenation in humans and to advance the benefits of renitrosylation therapy on oxygen delivery through the following aims: 1. To further advance understanding of the molecular mechanisms by which RBCs export SNO bioactivity to regulate tissue oxygenation; 2. To develop a device for controlled ex vivo renitrosylation; 3. To determine if renitrosylation can improve post-surgical outcome in an animal model of pediatric bypass; and 4. To conduct an autologous transfusion study in humans to determine the benefits of renitrosylation on tissue oxygenation. Collectively, our studies should provide much-needed insight into the effects of transfusion on tissue oxygenation, shed light on the mechanistic basis of adverse ischemic events associated with transfusion, and accelerate development of therapeutic approaches (repletion of SNO-Hb). Restoration of the oxygen delivery capabilities of banked blood should result in blood transfusion achieving its clinical purpose: vasodilation in the microcirculation to improve end-organ oxygen delivery in the anemic patient. To the extent that the world’s supplies of banked RBCs are deficient in SNO-Hb, renitrosylation may hold significant therapeutic promise.
项目总结

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 }}

JONATHAN S. STAMLER其他文献

JONATHAN S. STAMLER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('JONATHAN S. STAMLER', 18)}}的其他基金

S-nitrosylation signaling in asthma
哮喘中的 S-亚硝基化信号传导
  • 批准号:
    10662243
  • 财政年份:
    2021
  • 资助金额:
    $ 56.72万
  • 项目类别:
S-nitrosylation signaling in asthma
哮喘中的 S-亚硝基化信号传导
  • 批准号:
    10457996
  • 财政年份:
    2021
  • 资助金额:
    $ 56.72万
  • 项目类别:
Gut Microbe-Derived Nitric Oxide As A Signal To Host: Role In Normal Physiology And In Disease
肠道微生物衍生的一氧化氮作为宿主信号:在正常生理和疾病中的作用
  • 批准号:
    10184663
  • 财政年份:
    2021
  • 资助金额:
    $ 56.72万
  • 项目类别:
S-nitrosylation signaling in asthma
哮喘中的 S-亚硝基化信号传导
  • 批准号:
    10269972
  • 财政年份:
    2021
  • 资助金额:
    $ 56.72万
  • 项目类别:
Gut Microbe-Derived Nitric Oxide As A Signal To Host: Role In Normal Physiology And In Disease
肠道微生物衍生的一氧化氮作为宿主信号:在正常生理和疾病中的作用
  • 批准号:
    10576352
  • 财政年份:
    2021
  • 资助金额:
    $ 56.72万
  • 项目类别:
Gut Microbe-Derived Nitric Oxide As A Signal To Host: Role In Normal Physiology And In Disease
肠道微生物衍生的一氧化氮作为宿主信号:在正常生理和疾病中的作用
  • 批准号:
    10357961
  • 财政年份:
    2021
  • 资助金额:
    $ 56.72万
  • 项目类别:
Novel Regulation of Renal Function by S-Nitrosylation
S-亚硝基化对肾功能的新调节
  • 批准号:
    9792377
  • 财政年份:
    2018
  • 资助金额:
    $ 56.72万
  • 项目类别:
Novel Regulation of Renal Function by S-Nitrosylation
S-亚硝基化对肾功能的新调节
  • 批准号:
    10453693
  • 财政年份:
    2018
  • 资助金额:
    $ 56.72万
  • 项目类别:
Novel Regulation of Renal Function by S-Nitrosylation
S-亚硝基化对肾功能的新调节
  • 批准号:
    10223283
  • 财政年份:
    2018
  • 资助金额:
    $ 56.72万
  • 项目类别:
Restoration and Function of S-Nitrosothiol in Stored Blood
储存血液中S-亚硝基硫醇的恢复和作用
  • 批准号:
    9174571
  • 财政年份:
    2016
  • 资助金额:
    $ 56.72万
  • 项目类别:

相似海外基金

Planar culture of gastrointestinal stem cells for screening pharmaceuticals for adverse event risk
胃肠道干细胞平面培养用于筛选药物不良事件风险
  • 批准号:
    10707830
  • 财政年份:
    2023
  • 资助金额:
    $ 56.72万
  • 项目类别:
Hospital characteristics and Adverse event Rate Measurements (HARM) Evaluated over 21 years.
医院特征和不良事件发生率测量 (HARM) 经过 21 年的评估。
  • 批准号:
    479728
  • 财政年份:
    2023
  • 资助金额:
    $ 56.72万
  • 项目类别:
    Operating Grants
Analysis of ECOG-ACRIN adverse event data to optimize strategies for the longitudinal assessment of tolerability in the context of evolving cancer treatment paradigms (EVOLV)
分析 ECOG-ACRIN 不良事件数据,以优化在不断发展的癌症治疗范式 (EVOLV) 背景下纵向耐受性评估的策略
  • 批准号:
    10884567
  • 财政年份:
    2023
  • 资助金额:
    $ 56.72万
  • 项目类别:
AE2Vec: Medical concept embedding and time-series analysis for automated adverse event detection
AE2Vec:用于自动不良事件检测的医学概念嵌入和时间序列分析
  • 批准号:
    10751964
  • 财政年份:
    2023
  • 资助金额:
    $ 56.72万
  • 项目类别:
Understanding the real-world adverse event risks of novel biosimilar drugs
了解新型生物仿制药的现实不良事件风险
  • 批准号:
    486321
  • 财政年份:
    2022
  • 资助金额:
    $ 56.72万
  • 项目类别:
    Studentship Programs
Pediatric Adverse Event Risk Reduction for High Risk Medications in Children and Adolescents: Improving Pediatric Patient Safety in Dental Practices
降低儿童和青少年高风险药物的儿科不良事件风险:提高牙科诊所中儿科患者的安全
  • 批准号:
    10676786
  • 财政年份:
    2022
  • 资助金额:
    $ 56.72万
  • 项目类别:
Pediatric Adverse Event Risk Reduction for High Risk Medications in Children and Adolescents: Improving Pediatric Patient Safety in Dental Practices
降低儿童和青少年高风险药物的儿科不良事件风险:提高牙科诊所中儿科患者的安全
  • 批准号:
    10440970
  • 财政年份:
    2022
  • 资助金额:
    $ 56.72万
  • 项目类别:
Improving Adverse Event Reporting on Cooperative Oncology Group Trials
改进肿瘤学合作组试验的不良事件报告
  • 批准号:
    10642998
  • 财政年份:
    2022
  • 资助金额:
    $ 56.72万
  • 项目类别:
Planar culture of gastrointestinal stem cells for screening pharmaceuticals for adverse event risk
胃肠道干细胞平面培养用于筛选药物不良事件风险
  • 批准号:
    10482465
  • 财政年份:
    2022
  • 资助金额:
    $ 56.72万
  • 项目类别:
Expanding and Scaling Two-way Texting to Reduce Unnecessary Follow-Up and Improve Adverse Event Identification Among Voluntary Medical Male Circumcision Clients in the Republic of South Africa
扩大和扩大双向短信,以减少南非共和国自愿医疗男性包皮环切术客户中不必要的后续行动并改善不良事件识别
  • 批准号:
    10191053
  • 财政年份:
    2020
  • 资助金额:
    $ 56.72万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了