Effects of Propofol on Endotoxin-Induced Acute Lung Injury in Rabbit

This study was undertaken to clarify the effects of propofol on endotoxin-induced acute lung injury. Rabbits were randomly assigned to one of four groups. Each group received intravenous infusion of saline only, saline and Escherichia coli endotoxin, propofol (1 mg/kg bolus, then 5 mg/kg/hr) and endotoxin, or propofol (4 mg/kg bolus, then 20 mg/kg/hr) and endotoxin respectively. Infusion of saline or propofol was started 0.5 hr before the infusion of saline or endotoxin, and continued for 6 hr thereafter. The lungs of rabbits were ventilated with 40% oxygen. Mean blood pressure, heart rate, arterial oxygen tension (PaO2), and peripheral blood leukocyte and platelet count were recorded. The wet/dry (W/D) weight ratio of lung and lung injury score were measured, and analysis of bronchoalveolar lavage fluid (BALF) was done. Endotoxin decreased PaO2, and peripheral blood leukocyte and platelet count. And it increased W/D ratio of lung, lung injury score and leukocyte count, percentage of PMN cells, concentration of albumin, thromboxane B2 and IL-8 in BALF. Propofol attenuated all these changes except the leukocyte count in peripheral blood. In conclusion, propofol attenuated endotoxin-induced acute lung injury in rabbits mainly by inhibiting neutrophil and IL-8 responses, which may play a central role in sepsis-related lung injury

The European Photon Imaging Camera on XMM-Newton: The MOS Cameras

The EPIC focal plane imaging spectrometers on XMM-Newton use CCDs to record the images and spectra of celestial X-ray sources focused by the three X-ray mirrors. There is one camera at the focus of each mirror; two of the cameras contain seven MOS CCDs, while the third uses twelve PN CCDs, defining a circular field of view of 30 arcmin diameter in each case. The CCDs were specially developed for EPIC, and combine high quality imaging with spectral resolution close to the Fano limit. A filter wheel carrying three kinds of X-ray transparent light blocking filter, a fully closed, and a fully open position, is fitted to each EPIC instrument. The CCDs are cooled passively and are under full closed loop thermal control. A radio-active source is fitted for internal calibration. Data are processed on-board to save telemetry by removing cosmic ray tracks, and generating X-ray event files; a variety of different instrument modes are available to increase the dynamic range of the instrument and to enable fast timing. The instruments were calibrated using laboratory X-ray beams, and synchrotron generated monochromatic X-ray beams before launch; in-orbit calibration makes use of a variety of celestial X-ray targets. The current calibration is better than 10% over the entire energy range of 0.2 to 10 keV. All three instruments survived launch and are performing nominally in orbit. In particular full field-of-view coverage is available, all electronic modes work, and the energy resolution is close to pre-launch values. Radiation damage is well within pre-launch predictions and does not yet impact on the energy resolution. The scientific results from EPIC amply fulfil pre-launch expectations.Comment: 9 pages, 11 figures, accepted for publication in the A&A Special Issue on XMM-Newto

Inhaled nitric oxide alleviates hyperoxia suppressed phosphatidylcholine synthesis in endotoxin-induced injury in mature rat lungs

BACKGROUND: We investigated efficacy of inhaled nitric oxide (NO) in modulation of metabolism of phosphatidylcholine (PC) of pulmonary surfactant and in anti-inflammatory mechanism of mature lungs with inflammatory injury. METHODS: Healthy adult rats were divided into a group of lung inflammation induced by i.v. lipopolysaccharides (LPS) or a normal control (C) for 24 h, and then exposed to: room air (Air), 95% oxygen (O), NO (20 parts per million, NO), both O and NO (ONO) as subgroups, whereas [(3)H]-choline was injected i.v. for incorporation into PC of the lungs which were processed subsequently at 10 min, 4, 8, 12 and 24 h, respectively, for measurement of PC synthesis and proinflammatory cytokine production. RESULTS: LPS-NO subgroup had the lowest level of labeled PC in total phospholipids and disaturated PC in bronchoalveolar lavage fluid and lung tissue (decreased by 46–59%), along with the lowest activity of cytidine triphosphate: phosphocholine cytidylyltransferase (-14–18%) in the lungs, compared to all other subgroups at 4 h (p < 0.01), but not at 8 and 12 h. After 24-h, all LPS-subgroups had lower labeled PC than the corresponding C-subgroups (p < 0.05). LPS-ONO had higher labeled PC in total phospholipids and disaturated PC, activity of cytidylyltransferase, and lower activity of nuclear transcription factor-κB and expression of proinflammatory cytokine mRNA, than that in the LPS-O subgroup (p < 0.05). CONCLUSION: In LPS-induced lung inflammation in association with hyperoxia, depressed PC synthesis and enhanced proinflammatory cytokine production may be alleviated by iNO. NO alone only transiently suppressed the PC synthesis as a result of lower activity of cytidylyltransferase

Biomarkers of acute lung injury: worth their salt?

The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI) and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy

Report of the American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee.

The acute respiratory distress syndrome (ARDS), a process of non-hydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies carries a high morbidity, mortality (10-90%) and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged and may be different in Europe. Part of the reason for these uncertainties is the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those whose wish to know the true incidence and outcome on this clinical syndrome are stymied. The European American Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS

The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination.

The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity, mortality (10 to 90%), and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged, and it may be different in Europe. Part of the reason for these uncertainties are the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those who wish to know the true incidence and outcome of this clinical syndrome are stymied. The American-European Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS