The lectin-like domain of tumor necrosis factor improves lung function after rat lung transplantation--potential role for a reduction in reactive oxygen species generation

To test the hypothesis that the lectin-like domain of tumor necrosis factor, mimicked by the TIP peptide, can improve lung function after unilateral orthotopic lung isotransplantation. Because of a lack of a specific treatment for ischemia reperfusion-mediated lung injury, accompanied by a disrupted barrier integrity and a dysfunctional alveolar liquid clearance, alternative therapies restoring these parameters after lung transplantation are required.

Hemodynamic parameters change earlier than tissue oxygen tension in hemorrhage

BACKGROUND: Untreated hypovolemia results in impaired outcome. This study tests our hypothesis whether general hemodynamic parameters detect acute blood loss earlier than monitoring parameters of regional tissue beds. MATERIALS AND METHODS: Eight pigs (23-25 kg) were anesthetized and mechanically ventilated. A pulmonary artery catheter and an arterial catheter were inserted. Tissue oxygen tension was measured with Clark-type electrodes in the jejunal and colonic wall, in the liver, and subcutaneously. Jejunal microcirculation was assessed by laser Doppler flowmetry (LDF). Intravascular volume was optimized using difference in pulse pressure (dPP) to keep dPP below 13%. Sixty minutes after preparation, baseline measurements were taken. At first, 5% of total blood volume was withdrawn, followed by another 5% increment, and then in 10% increments until death. RESULTS: After withdrawal of 5% of estimated blood volume, dPP increased from 6.1% +/- 3.0% to 20.8% +/- 2.7% (P < 0.01). Mean arterial pressure (MAP), mean pulmonary artery pressure (PAP) and pulmonary artery occlusion pressure (PAOP) decreased with a blood loss of 10% (P < 0.01). Cardiac output (CO) changed after a blood loss of 20% (P < 0.05). Tissue oxygen tension in central organs, and blood flow in the jejunal muscularis decreased (P < 0.05) after a blood loss of 20%. Tissue oxygen tension in the skin, and jejunal mucosa blood flow decreased (P < 0.05) after a blood loss of 40% and 50%, respectively. CONCLUSIONS: In this hemorrhagic pig model systemic hemodynamic parameters were more sensitive to detect acute hypovolemia than tissue oxygen tension measurements or jejunal LDF measurements. Acute blood loss was detected first by dPP.

500 ml of blood loss does not decrease non-invasive tissue oxygen saturation (StO2) as measured by near infrared spectroscopy - A hypothesis generating pilot study in healthy adult women

Background The goal when resuscitating trauma patients is to achieve adequate tissue perfusion. One parameter of tissue perfusion is tissue oxygen saturation (StO2), as measured by near infrared spectroscopy. Using a commercially available device, we investigated whether clinically relevant blood loss of 500 ml in healthy volunteers can be detected by changes in StO2 after a standardized ischemic event. Methods We performed occlusion of the brachial artery for 3 minutes in 20 healthy female blood donors before and after blood donation. StO2 and total oxygenated tissue hemoglobin (O2Hb) were measured continuously at the thenar eminence. 10 healthy volunteers were assessed in the same way, to examine whether repeated vascular occlusion without blood donation exhibits time dependent effects. Results Blood donation caused a substantial decrease in systolic blood pressure, but did not affect resting StO2 and O2Hb values. No changes were measured in the blood donor group in the reaction to the vascular occlusion test, but in the control group there was an increase in the O2Hb rate of recovery during the reperfusion phase. Conclusion StO2 measured at the thenar eminence seems to be insensitive to blood loss of 500 ml in this setting. Probably blood loss greater than this might lead to detectable changes guiding the treating physician. The exact cut off for detectable changes and the time effect on repeated vascular occlusion tests should be explored further. Until now no such data exist.

[Management of oxygen delivery and consumption during sepsis]

Maintaining an adequate tissue oxygen delivery (DO(2)) and consumption (VO(2)) is crucial in the treatment of septic patients. A fall in V0(2) is associated with a higher mortality. The early recognition of shock or tissue hypo perfusion impacts on patient prognosis. In occasions, hypovolemia or important regional oxygen debts are not recognized, since macro homodynamic variables have been compensated. In this situation, the use of metabolic hypo perfusion markers such as lactate, central venous oxygen saturation and gastric goniometry, can be helpful. However, interpretation of these markers should be cautious and always considering the overall clinical status of the patient. In the initial stages of sepsis, the dependency of V0(2) on DO(2) predominates as histopathological mechanism of multiple organic failure. In late stages, other factors predominate as determinants of multiple organic failure and mortality, such as hyper or hypo immune response, microcirculatory alterations and cytopathic hypoxia.

Reactive oxygen species mediate functional differences in human radial and internal thoracic arteries from smokers

Smoking not only increases the risk that coronary heart disease will develop but also morbidity and mortality in patients with known coronary atherosclerosis and after coronary artery bypass grafting. Excessive generation of reactive oxygen species (ROS) has been implicated as the final common pathway for the development of endothelial dysfunction in various cardiovascular risk factors. This study assessed the influence of smoking on two different human arteries routinely used as coronary artery bypass graft conduits.

Loss of sphingosine kinase-1 in carcinoma cells increases formation of reactive oxygen species and sensitivity to doxorubicin-induced DNA damage

Sphingosine kinases (SK) catalyse the formation of sphingosine 1-phosphate, which is a key lipid mediator regulating cell responses such as proliferation, survival and migration. Here we have investigated the effect of targeted inhibition of SK-1 on cell damage and elucidated the mechanisms involved.

Charge transfer reactions of organic ions containing oxygen: Correlation between reaction energetics and cross sections

Cross sections for charge transfer reactions of organic ions containing oxygen have been obtained using time-of-flight techniques. Charge transfer cross sections have been determined for reactions of 2.0 to 3.4 keV ions produced by electron impact ionization of oxygen containing molecules such as methanol, ethanal and ethanol. Experimental cross section magnitudes have been correlated with reaction energy defects computed from ion recombination energies and target ionization energies. Large cross sections are observed for reacting systems with small energy defects.

The copper-inducible ComR (YcfQ) repressor regulates expression of ComC (YcfR), which affects copper permeability of the outer membrane of Escherichia coli

The pathway of copper entry into Escherichia coli is still unknown. In an attempt to shed light on this process, a lux-based biosensor was utilized to monitor intracellular copper levels in situ. From a transposon-mutagenized library, strains were selected in which copper entry into cells was reduced, apparent as clones with reduced luminescence when grown in the presence of copper (low-glowers). One low-glower had a transposon insertion in the comR gene, which encodes a TetR-like transcriptional regulator. The mutant strain could be complemented by the comR gene on a plasmid, restoring luminescence to wild-type levels. ComR did not regulate its own expression, but was required for copper-induction of the neighboring, divergently transcribed comC gene, as shown by real-time quantitative PCR and with a promoter-lux fusion. The purified ComR regulator bound to the promoter region of the comC gene in vitro and was released by copper. By membrane fractionation, ComC was shown to be localized in the outer membrane. When grown in the presence of copper, ∆comC cells had higher periplasmic and cytoplasmic copper levels, compared to the wild-type, as assessed by the activation of the periplasmic CusRS sensor and the cytoplasmic CueR sensor, respectively. Thus, ComC is an outer membrane protein which lowers the permeability of the outer membrane to copper. The expression of ComC is controlled by ComR, a novel, TetR-like copper-responsive repressor.