Abstract:
OBJECTIVE:Effective therapies are needed to reverse the increased vascular permeability that characterizes acute inflammatory diseases such as acute lung injury. FTY720 is a pharmaceutical analog of the potent barrier-enhancing phospholipid, sphingosine 1-phosphate. Because both FTY720 and sphingosine 1-phosphate have properties that may limit their usefulness in patients with acute lung injury, alternative compounds are needed for therapeutic use. The objective of this study is to characterize the effects of FTY720 (S)-phosphonate, a novel analog of FTY720-phosphate, on variables of pulmonary vascular permeability in vitro and alveolar-capillary permeability in vivo. SETTING:University-affiliated research institute. SUBJECTS:Cultured human pulmonary endothelial cells; C57BL/6 mice. INTERVENTIONS:Endothelial cells were stimulated with sphingosine 1-phosphate receptor 1 agonists to determine effects on sphingosine 1-phosphate receptor 1 expression. Acute lung injury was induced in C57BL/6 mice with bleomycin to assess effects of sphingosine 1-phosphate receptor 1 agonists. MEASUREMENTS AND MAIN RESULTS:FTY720 (S)-phosphonate potently increases human pulmonary endothelial cell barrier function in vitro as measured by transendothelial electrical resistance. Reduction of sphingosine 1-phosphate receptor 1 with small interference RNA significantly attenuates this transendothelial electrical resistance elevation. FTY720 (S)-phosphonate maintains endothelial sphingosine 1-phosphate receptor 1 protein expression in contrast to greater than 50% reduction after incubation with sphingosine 1-phosphate, FTY720, or other sphingosine 1-phosphate receptor 1 agonists. FTY720 (S)-phosphonate does not induce β-arrestin recruitment, sphingosine 1-phosphate receptor 1 ubiquitination, and proteosomal degradation that occur after other agonists. Intraperitoneal administration of FTY720 (S)-phosphonate every other day for 1 week in normal or bleomycin-injured mice maintains significantly higher lung sphingosine 1-phosphate receptor 1 expression compared with FTY720. FTY720 fails to protect against bleomycin-induced acute lung injury in mice, while FTY720 (S)-phosphonate significantly decreases lung leak and inflammation. CONCLUSION:FTY720 (S)-phosphonate is a promising barrier-promoting agent that effectively maintains sphingosine 1-phosphate receptor 1 levels and improves outcomes in the bleomycin model of acute lung injury.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Wang L,Sammani S,Moreno-Vinasco L,Letsiou E,Wang T,Camp SM,Bittman R,Garcia JG,Dudek SMdoi
10.1097/CCM.0000000000000097subject
Has Abstractpub_date
2014-03-01 00:00:00pages
e189-99issue
3eissn
0090-3493issn
1530-0293journal_volume
42pub_type
杂志文章abstract:OBJECTIVE:To evaluate the impact of a newly appointed neurointensivist on neurosciences intensive care unit (NICU) patient outcomes and quality of care variables. DESIGN:Observational cohort with historical controls. SETTING:Ten-bed neurointensive care unit in tertiary university hospital. PATIENTS:Mortality, length...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.ccm.0000146131.03578.21
更新日期:2004-11-01 00:00:00
abstract:OBJECTIVES:The purpose of this study was to determine the accuracy of clinical diagnoses compared to autopsy findings in critically ill patients in the current medical era. DESIGN:We conducted a retrospective, blinded review of matched medical records and postmortem findings in patients who died between June 2006 and ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3182a275b1
更新日期:2014-02-01 00:00:00
abstract::The effects of PEEP and subsequent augmentation of cardiac output by sodium nitroprusside (SNP) were examined in a canine model of asymmetric oleic acid injury to the right lung. PEEP (9.2 +/- 0.5 cm H2O) was added to six animals to decrease venous admixture (Qsp/Qt) from 50.6 +/- 4.4% to 16.0 +/- 1.3% (p less than .0...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198903000-00008
更新日期:1989-03-01 00:00:00
abstract::Clinical impressions about the problem of defibrillation during states of acid-base imbalance and hypoxia have been influenced by studies involving the effect of these derangements on the ventricular fibrillation threshold. Based on body weight, energy requirements for defibrillation in normal dogs were compared to re...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-197507000-00003
更新日期:1975-07-01 00:00:00
abstract::Perfluorocarbon (PFC) emulsions are promising oxygen-carrying blood supplements for the treatment of shock and in organ preservation for transplantation. We used the isolated, blood-perfused, canine right lower lung lobe (RLL) to determine the effect of a PFC emulsion, Oxypherol (FC-43), upon lung fluid balance and he...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198512000-00006
更新日期:1985-12-01 00:00:00
abstract:OBJECTIVE:To describe a case of intentional ingestion of hand sanitizer in our hospital and to review published cases and those reported to the American Association of Poison Control Centers' National Poison Data System. DESIGN:A case report, a literature review of published cases, and a query of the National Poison D...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/CCM.0b013e31822f09c0
更新日期:2012-01-01 00:00:00
abstract:OBJECTIVES:To review the intensive care unit experience of patients with admitted or acquired nosocomial endocarditis (NE) defined according to the Duke criteria. DESIGN:Prospective, cohort study. SETTING:University teaching hospital. PATIENTS:We reviewed the records of 22 patients documented with NE during a 6-yr p...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200002000-00015
更新日期:2000-02-01 00:00:00
abstract:OBJECTIVES:In acute respiratory distress syndrome, conservative fluid management increases ventilator-free days without affecting mortality. Response to fluid management may differ based on patients' initial central venous pressure. We hypothesized that initial central venous pressure would modify the effect of fluid m...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001555
更新日期:2016-04-01 00:00:00
abstract:OBJECTIVE:In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were "to provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious pr...
journal_title:Critical care medicine
pub_type: 共识发展会议,杂志文章,评审
doi:10.1097/01.CCM.0000050454.01978.3B
更新日期:2003-04-01 00:00:00
abstract:OBJECTIVE:Pathogens that cause pneumonia may be treated in a targeted fashion by antibiotics, but if this therapy fails, then treatment involves only nonspecific supportive measures, independent of the inciting infection. The purpose of this study was to determine whether host response is similar after disparate infect...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181b4a76b
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVES:To investigate the effects of recombinant human erythropoietin on brain oxygenation in a model of diffuse traumatic brain injury. DESIGN:Adult male Wistar rats. SETTING:Neurosciences and physiology laboratories. INTERVENTIONS:Thirty minutes after diffuse traumatic brain injury (impact-acceleration model),...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e31827ca64e
更新日期:2013-05-01 00:00:00
abstract::Twenty-four pediatric patients undergoing corrective posterior spinal fusion surgery for idiopathic scoliosis were studied to determine the frequency with which the syndrome of inappropriate antidiuretic hormone secretion (SIADH) developed. We measured arterial blood gases, serum and urine electrolytes and osmolalitie...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198307000-00009
更新日期:1983-07-01 00:00:00
abstract:OBJECTIVES:Sepsis results in organ dysfunction caused by a dysregulated host response, in part related to the immune response of a severe infection. Mesenchymal stromal cells are known to modulate the immune response, and expression of stromal cell-derived factor-1 regulates mobilization of neutrophils from the bone ma...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000004244
更新日期:2020-05-01 00:00:00
abstract:OBJECTIVE:To review the history and development of critical care nurses, the supply and demand issues related to critical care nursing, critical care nursing's contribution to patient outcomes, and recommendations to ensure a steady and strong workforce. DATA SOURCE AND SELECTION:Information presented in this article ...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/01.CCM.0000203087.42439.53
更新日期:2006-03-01 00:00:00
abstract:OBJECTIVES:Given the efficacy and safety of recombinant human activated protein C (rhAPC) in the systemic inflammatory response syndrome, this study was designed to review the evidence for a role for APC in the pathogenesis of preeclampsia. Preeclampsia is a proinflammatory and procoagulant state, and it is a pregnancy...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验,评审
doi:10.1097/00003246-200208000-00035
更新日期:2002-08-01 00:00:00
abstract:OBJECTIVES:To determine whether delirium during ICU stay is associated with long-term mental health problems defined as symptoms of anxiety, depression, and posttraumatic stress disorder. DESIGN:Prospective cohort study. SETTING:Survey study, 1 year after discharge from a medical-surgical ICU in the Netherlands. PAT...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001861
更新日期:2016-10-01 00:00:00
abstract:OBJECTIVES:To study the relation between nitrite, nitrate, nitrotyrosine, and nitrosothiols as NO indices in human septic shock. DESIGN:A prospective clinical study. SETTING:Intensive care units in a university hospital and a central county hospital. PATIENTS:Sixteen patients admitted for septic shock. Nine healthy ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200008000-00017
更新日期:2000-08-01 00:00:00
abstract:OBJECTIVE:Artery puncture and hematoma formation are the most common immediate complications during internal jugular vein catheterization. This study was performed to assess whether the bevel-down approach of the puncture needle decreases the incidence of posterior venous wall damage and hematoma formation during inter...
journal_title:Critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1097/CCM.0b013e318232da48
更新日期:2012-02-01 00:00:00
abstract:OBJECTIVE:To compare the scales and predictive power for hospital mortality of three recent multiple organ dysfunction scores. DESIGN:Prospective, observational, validation cohort study. SETTING:A ten-bed medical-surgical intensive care unit in a Finnish tertiary care hospital. PATIENTS:Among the 591 consecutive pat...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200208000-00005
更新日期:2002-08-01 00:00:00
abstract::The image of the physician as a therapist, as well as the general perception of the physician's role in society and in the life of patients and their families, has changed dramatically in past decades. In response, many conferences, editorials, and planning activities for medical and premedical curricula have been dev...
journal_title:Critical care medicine
pub_type: 传,历史文章,杂志文章
doi:10.1097/00003246-198810000-00012
更新日期:1988-10-01 00:00:00
abstract::Because determining cardiac output is difficult in premature infants, little is known about the hemodynamic effects of PEEP in this age group. We used pulsed-wave Doppler echocardiography to assess the hemodynamic effects of PEEP increments in ten premature infants with respiratory distress syndrome. At a PEEP of 4 cm...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198707000-00007
更新日期:1987-07-01 00:00:00
abstract:OBJECTIVES:Venovenous extracorporeal gas exchange is increasingly used in awake, spontaneously breathing patients as a bridge to lung transplantation. Limited data are available on a similar use of extracorporeal gas exchange in patients with acute respiratory distress syndrome. The aim of this study was to investigate...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000121
更新日期:2014-03-01 00:00:00
abstract:OBJECTIVE:When a patient is incompetent, the family is often considered to be a natural surrogate. The doctors' responsiveness to family wishes may vary. We explored if doctors' personal characteristics were associated with responsiveness to the relatives' wishes when admission to the intensive care unit (ICU) is consi...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181958409
更新日期:2009-02-01 00:00:00
abstract:OBJECTIVE:Persistent pulmonary hypertension of the newborn is characterized by the presence of intense vasoconstriction and vascular remodeling. Protein tyrosine phosphorylation has been recognized as a critical regulatory element in signal transduction, because it is dynamically regulated by the opposing actions of pr...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00003246-200106000-00030
更新日期:2001-06-01 00:00:00
abstract:OBJECTIVE:To assess the efficacy of bulk diffusion in maintaining oxygenation during apnea testing for brain death. DESIGN:Case series. SETTING:ICU in a primary care hospital. PATIENTS:Twenty-four consecutive patients with suspected brain death. Most patients suffered cerebral trauma from vehicular accidents. INTER...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199211000-00014
更新日期:1992-11-01 00:00:00
abstract:OBJECTIVES:Approximately one in every four patients who present to the emergency department with sepsis progresses to septic shock within 72 hours of arrival. In this study, we describe key patient characteristics present within 4 hours of emergency department arrival that are associated with developing septic shock be...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000861
更新日期:2015-05-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that the mortality rate of acutely ill patients admitted to a medical ward or medical ICU is higher for those patients who present with hypomagnesemia than for those patients who do not present with hypomagnesemia. DESIGN:Prospective, observational study. SETTING:Emergency Department ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199302000-00010
更新日期:1993-02-01 00:00:00
abstract::We developed a method to measure accurately pressures at the airway opening (Pao) and in the trachea (Ptr) in neonates during high frequency oscillatory ventilation (HFOV) from 15-30 Hz. All component parts of the pressure-measuring system were tested as a unit against a reference transducer in a closed chamber in whi...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198401000-00011
更新日期:1984-01-01 00:00:00
abstract::The use of epidural opioids for postoperative analgesia has been associated with respiratory depression. This report demonstrates the ability of nalbuphine to rapidly reverse the respiratory depression caused by epidural sufentanil while maintaining postoperative pain relief. ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198904000-00017
更新日期:1989-04-01 00:00:00
abstract::Arterial catheterization for blood gas analysis and direct monitoring of blood pressure in infants and children can be attended by a variety of complications, which limit its use to short periods of time. An improved technique, consisting of elimination of stopcocks, the use of a continuous flushing system adapted for...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-197605000-00010
更新日期:1976-05-01 00:00:00