Abstract:
OBJECTIVE:Sepsis-induced multi-organ failure continues to have a high mortality. The liver is an organ central to the disease pathogenesis. The objective of this study was to identify the liver proteins that change in abundance with sepsis and subsequently identify new drug targets. DESIGN:Proteomic discovery study and drug target validation. For the proteomics study, three biological replicate mice were used per group. SETTING:Research institute laboratory. SUBJECTS:Three-month-old C57BL/6 mice. INTERVENTIONS:We used a mouse model of sepsis based on cecal ligation and puncture, but with fluid and antibiotic resuscitation. Liver proteins that changed in abundance were identified by difference in gel electrophoresis. We compared liver proteins from 6-hr post-cecal ligation and puncture to sham-operated mice ("early proteins") and 24-hr post-cecal ligation and puncture with 6-hr post-cecal ligation and puncture ("late proteins"). Proteins that changed in abundance were identified by tandem mass spectrometry. We then inhibited the receptor for one protein and determined the effect on sepsis-induced organ dysfunction. RESULTS:The liver proteins that changed in abundance after sepsis had a range of functions such as acute phase response, coagulation, endoplasmic reticulum stress, oxidative stress, apoptosis, mitochondrial electron transfer proteins, and nitric oxide metabolism. We found that cyclophilin increased in abundance after cecal ligation and puncture. When the receptor for this protein, CD147, was inhibited, sepsis-induced renal dysfunction was reduced. There was also a significant reduction in serum cytokine production when CD147 was inhibited. CONCLUSION:By applying proteomics to a clinically relevant mouse model of sepsis, we identified a number of novel proteins that changed in abundance. The inhibition of the receptor for one of these proteins, cyclophilin, attenuated sepsis-induced acute renal failure. The application of proteomics to sepsis research can facilitate the discovery of new therapeutic targets.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Dear JW,Leelahavanichkul A,Aponte A,Hu X,Constant SL,Hewitt SM,Yuen PS,Star RAdoi
10.1097/01.ccm.0000281858.44387.a2subject
Has Abstractpub_date
2007-10-01 00:00:00pages
2319-28issue
10eissn
0090-3493issn
1530-0293journal_volume
35pub_type
杂志文章abstract:OBJECTIVE:As the Surviving Sepsis Campaign was assessing patient-level data over multiple countries, we sought to evaluate the use of a pragmatic and parsimonious severity-of-illness scoring system for patients with sepsis in an attempt to provide appropriate comparisons with practical application. DESIGN:Prospective,...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000416
更新日期:2014-09-01 00:00:00
abstract:OBJECTIVE:This study evaluates the ability of perflubron to inhibit pulmonary neutrophil accumulation during partial liquid ventilation (PLV) in the setting of acute lung injury. DESIGN:Randomized, controlled, nonblinded study. SETTING:Research laboratory at a university. SUBJECTS:Male, Sprague-Dawley rats (n = 120,...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199810000-00028
更新日期:1998-10-01 00:00:00
abstract::Critical care clinicians no longer consider family members as visitors in the intensive care unit. Family-centered care has emerged from the results of qualitative and quantitative studies evaluating the specific needs of families of patients dying in the intensive care unit. In addition, interventional studies have e...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/01.CCM.0000237049.44246.8C
更新日期:2006-11-01 00:00:00
abstract:OBJECTIVES:To describe long-term survival in patients with severe acute respiratory distress syndrome and assess differences in patient characteristics and outcomes among those who receive rescue therapies (prone position ventilation, inhaled nitric oxide, or inhaled epoprostenol) versus conventional treatment. DESIGN...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000322
更新日期:2014-07-01 00:00:00
abstract::Eleven patients in hypertensive crisis were treated with iv sodium nitroprusside (SNP). In all cases, rapid clinical improvement was obtained. Nevertheless, 9 patients developed progressive resistance to the hypotensive effect of the drug. For the first 2 h, the mean infusion rate was 1.68 +/- 0.64 micrograms/kg . min...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198205000-00002
更新日期:1982-05-01 00:00:00
abstract:UNLABELLED:Meningococcal septic shock (MSS) has high mortality and morbidity rates. In addition to the traditional prompt antibiotics and respiratory and circulatory support, new treatment strategies have been proposed. AGAINST THE INFLAMMATORY CASCADE:Immunotherapy, such as antiserum to Escherichia coli J5 and human ...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/00003246-200009001-00013
更新日期:2000-09-01 00:00:00
abstract:OBJECTIVES:To compare 1-year all-cause mortality and major adverse cardiovascular events in cardiac arrest survivors with and without posttraumatic stress disorder symptomatology at hospital discharge. DESIGN:Prospective, observational cohort. SETTING:ICUs at a tertiary-care center. PATIENTS:Adults with return of sp...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000003713
更新日期:2019-06-01 00:00:00
abstract::A survey of acute care/blood gas laboratories was conducted through the memberships of the Society of Critical Care Medicine ( SCCM ) and the National Association of Medical Directors of Respiratory Care ( NAMDRC ). Data were obtained from 227 laboratories and analyzed for operational characteristics, personnel, analy...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198406000-00014
更新日期:1984-06-01 00:00:00
abstract::An emergency cricothyrotomy device was placed in 11 anesthetized dogs in order to assess airway damage and problems in placement, ventilation, and design. Posterior airway perforation without esophageal damage occurred in three animals. Submucosal hematomas or cricoid cartilage injury occurred in seven animals. As pla...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198702000-00016
更新日期:1987-02-01 00:00:00
abstract::Significant resistance was encountered when an attempt was made to withdraw a persistently wedged pulmonary artery catheter. A small amount of air was injected into the balloon lumen with great difficulty. This injection freed the catheter which was removed, but produced significant sudden hemoptysis and a pneumothora...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198106000-00013
更新日期:1981-06-01 00:00:00
abstract:OBJECTIVE:To develop clinical practice guidelines for the use of restraining therapies to maintain physical and psychological safety of adult and pediatric patients in the intensive care unit. PARTICIPANTS:A multidisciplinary, multispecialty task force of experts in critical care practice was convened from the members...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/01.CCM.0000095463.72353.AD
更新日期:2003-11-01 00:00:00
abstract:OBJECTIVE:To evaluate the use of enriched thioglycolate as a transport medium of protected specimen brush samples, in particular its value in direct examination of respiratory specimens and in guiding initial antibiotic prescription. DESIGN:Prospective, randomized, pilot study. SETTING:Medical-surgical teaching inten...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00003246-200202000-00008
更新日期:2002-02-01 00:00:00
abstract:OBJECTIVES:Cardiac arrest etiology may be an important source of between-patient heterogeneity, but the impact of etiology on organ injury is unknown. We tested the hypothesis that asphyxial cardiac arrest results in greater neurologic injury than cardiac etiology cardiac arrest (ventricular fibrillation cardiac arrest...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000003070
更新日期:2018-06-01 00:00:00
abstract:OBJECTIVE:This study tested the hypothesis that intra-coronary transfusion of circulation-derived autologous CD34+ cells can improve ischemia-related left ventricular dysfunction in patients with severe diffuse coronary artery disease refractory to medication and unsuitable for coronary intervention. DESIGN:A prospect...
journal_title:Critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1097/CCM.0000000000001138
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVE:To investigate the impact of circulating histones on cardiac injury and dysfunction in a murine model and patients with sepsis. DESIGN:Prospective, observational clinical study with in vivo and ex vivo translational laboratory investigations. SETTING:General ICU and university research laboratory. SUBJECTS...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001162
更新日期:2015-10-01 00:00:00
abstract::A small, double-blind crossover study compared the efficacy of aminophylline and doxapram in ventilator weaning of eight premature infants recovering from respiratory distress syndrome (RDS). Although neither drug was significantly better than the other, four infants were weaned from mechanical ventilation after drug ...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1097/00003246-198502000-00016
更新日期:1985-02-01 00:00:00
abstract:PURPOSES:To discuss the theoretical relationship of mean alveolar pressure to its most easily measured analog, the mean airway pressure, and to describe the key determinants, measurement considerations, and clinical implications of this index. DATA SOURCES:Relevant articles from the medical and physiologic literature,...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to highlight the link between induced hypothermia and increased survival duration as observed in the septic model developed by the laboratory. To reach this objective, survival duration and blood oxygen transport capacity were measured at two temperatures-38 °C (induced normothermia...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3182373134
更新日期:2012-03-01 00:00:00
abstract:OBJECTIVES:To characterize the rates of accidental removal of endotracheal tubes, nasogastric tubes, central venous catheters, and arterial catheters. To assess the efficacy of corrective measures aimed at reducing the accidental removal of these devices. DESIGN:Prospective, observational, and interventional study. S...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200001000-00010
更新日期:2000-01-01 00:00:00
abstract:OBJECTIVE:Subarachnoid hemorrhage results in significant long-lasting neurologic sequelae. Here, we investigated whether human albumin improves long-term outcomes in experimental subarachnoid hemorrhage and whether neurovascular remodeling is involved in the protection of albumin. DESIGN:Laboratory investigation. SET...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001193
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVES:Administration of eicosapentaenoic acid and docosahexanoic acid, omega-3 fatty acids in fish oil, has been associated with improved patient outcomes in acute lung injury when studied in a commercial enteral formula. However, fish oil has not been tested independently in acute lung injury. We therefore sought...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/CCM.0b013e318218669d
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVES:The electronic health record is a primary source of information for all professional groups participating in ICU rounds. We previously demonstrated that, individually, all professional groups involved in rounds have significant blind spots in recognition of patient safety issues in the electronic health reco...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000003302
更新日期:2018-10-01 00:00:00
abstract:OBJECTIVE:To determine the relationship between sublingual and intestinal mucosal microcirculatory perfusion. DESIGN:Observational, experimental study. SETTING:University-affiliated large animal laboratory. SUBJECTS:Ten fasted, anesthetized, mechanically ventilated, male pigs randomized to a sham group (n = 3) or to...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181b029c1
更新日期:2009-11-01 00:00:00
abstract:OBJECTIVES:To evaluate the impact of an emergency department mechanical ventilation protocol on clinical outcomes and adherence to lung-protective ventilation in patients with acute respiratory distress syndrome. DESIGN:Quasi-experimental, before-after trial. SETTING:Emergency department and ICUs of an academic cente...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002268
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVE:Traumatic brain injury contributes to morbidity and mortality in children and boys are disproportionately represented. Hypotension is common and worsens outcome after traumatic brain injury. Extracellular signal-related kinase mitogen-activated protein kinase is upregulated and reduces cerebral blood flow aft...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181e8ac1a
更新日期:2010-09-01 00:00:00
abstract::The right atrial pressure (Pra) was compared to the pulmonary capillary wedge pressure (Pcw) in 54 patients. In patients with heart disease, the correlation of Pra with Pcw was poor. However, in patients without clinical heart disease, Pra approximated Pcw, in both absolute number and change. This finding was independ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-197805000-00010
更新日期:1978-05-01 00:00:00
abstract::Vecuronium's short half-life and minimal cardiopulmonary side-effects make it a suitable drug for continuous infusion. Vecuronium is used frequently in critically ill patients to increase their total compliance and to minimize the adverse effects of mechanical ventilation. This crossover, prospective study evaluates t...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00003246-198910000-00004
更新日期:1989-10-01 00:00:00
abstract:OBJECTIVES:To describe the physiologic mechanisms of ventilator-induced lung injury and to define the major ventilator and host-dependent risk factors that contribute to such injury. DATA SOURCE:Basic science and clinical studies related to ventilator-induced barotrauma and lung pathophysiology. STUDY SELECTION:Empha...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/00003246-199301000-00024
更新日期:1993-01-01 00:00:00
abstract::A difference between potassium concentrations in arterial plasma and venous serum was evaluated. The difference was 0.5 mM/litre, with a range of 0.1 to 1.1 mM/liter. Multiple factors operating primarily upon the venous sample are responsible for this difference. The value for arterial plasma potassium is stable and p...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-197809000-00008
更新日期:1978-09-01 00:00:00
abstract:OBJECTIVE:To test the effects of three hemoglobin solutions on liver function and hepatic morphology after resuscitation from severe hemorrhagic shock. DESIGN:Prospective study. SETTING:Laboratory. SUBJECTS:Thirty-three beagle dogs. INTERVENTION:Hemorrhagic shock was induced in anesthetized dogs by removal of blood...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199604000-00019
更新日期:1996-04-01 00:00:00