Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury.

OBJECTIVE: To investigate the role of recombinant bactericidal/permeability-increasing protein (rBPI21) in the attenuation of the sepsis syndrome and acute lung injury associated with lower limb ischemia-reperfusion (I/R) injury. SUMMARY BACKGROUND DATA: Gut-derived endotoxin has been implicated in the conversion of the sterile inflammatory response to a lethal sepsis syndrome after lower torso I/R injury. rBPI21 is a novel antiendotoxin therapy with proven benefit in sepsis. METHODS: Anesthetized ventilated swine underwent midline laparotomy and bilateral external iliac artery occlusion for 2 hours followed by 2.5 hours of reperfusion. Two groups (n = 6 per group) were randomized to receive, by intravenous infusion over 30 minutes, at the start of reperfusion, either thaumatin, a control-protein preparation, at 2 mg/kg body weight, or rBPI21 at 2 mg/kg body weight. A control group (n = 6) underwent laparotomy without further treatment and was administered thaumatin at 2 mg/kg body weight after 2 hours of anesthesia. Blood from a carotid artery cannula was taken every half-hour for arterial blood gas analysis. Plasma was separated and stored at -70 degrees C for later determination of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 by bioassay, and IL-8 by enzyme-linked immunosorbent assay (ELISA), as a markers of systemic inflammation. Plasma endotoxin concentration was measured using ELISA. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. Bronchoalveolar lavage protein concentration was measured by the bicinclinoic acid method as a measure of capillary-alveolar protein leak. The alveolar-arterial gradient was measured; a large gradient indicated impaired oxygen transport and hence lung injury. RESULTS: Bilateral hind limb I/R injury increased significantly intestinal mucosal acidosis, intestinal permeability, portal endotoxemia, plasma IL-6 concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, edema, capillary-alveolar protein leak, and impaired gas exchange. Conversely, pigs treated with rBPI21 2 mg/kg at the onset of reperfusion had significantly reduced intestinal mucosal acidosis, portal endotoxin concentrations, and circulating phagocytic cell priming and had significantly less pulmonary edema, leukosequestration, and respiratory failure. CONCLUSIONS: Endotoxin transmigration across a hyperpermeable gut barrier, phagocytic cell priming, and cytokinemia are key events of I/R injury, sepsis, and pulmonary dysfunction. This study shows that rBPI21 ameliorates these adverse effects and may provide a novel therapeutic approach for prevention of I/R-associated sepsis syndrome.

Opacity in the upper atmosphere of AU Mic

In this paper we investigate the validity of the optically thin assumption in the transition region of the late-type star AU Mic. We use Far-Ultraviolet Spectroscopic Explorer (FUSE) observations of the C III multiplet and O VI resonance lines, hence yielding information at two different levels within the atmosphere. Significant deviations from the optically thin fluxes are found for C III in both quiescent and flare spectra, where only 60% of the flux is actually observed. This could explain the apparent deviation of C III observed in emission measure distributions. We utilize escape probabilities for both homogeneous and inhomogeneous geometries and calculate optical depths as high as 10 for the C III 1175.71 Angstrom component of the multiplet. Using a lower limit to the electron density (10(11) cm(-3))we derive an effective thickness of

A detailed study of opacity in the upper atmosphere of Proxima Centauri

We present far-UV and UV spectroscopic observations of Proxima Centauri obtained as part of our continued investigation into the optically thin approximation assumed for the transition regions of late-type stars. Significant opacity is found in the C III lines during both the quiescent and flaring states of Proxima Cen, with up to 70% of the expected flux being lost in the latter. Our findings cast some doubt on the suitability of the C III lambda977 line for estimating the electron density in stellar atmospheres. However, the opacity has no significant effect on the observed line widths. We calculate optical depths for homogeneous and inhomogeneous geometries and estimate an electron density of 6 x 10(10) cm(-3) for the transition region using the O IV line ratios at 1400 Angstrom. The combination of electron density and optical depth indicates path lengths as low as approximate to 10 km, which are in excellent agreement with estimates of the small-scale structure seen in the solar transition region.

Opacity in the upper atmospheres of active stars - II. AD Leonis

We present FUV and UV spectroscopic observations of AD Leonis, with the aim of investigating opacity effects in the transition regions of late-type stars. The C III lines in FUSE spectra show significant opacity during both the quiescent and flaring states of AD Leonis, with up to 30% of the expected flux being lost during the latter. Other FUSE emission lines tested for opacity include those of O VI, while C IV, Si IV and N V transitions observed with STIS are also investigated. These lines only reveal modest amounts of opacity with losses during flaring of up to 20%. Optical depths have been calculated for homogeneous and inhomogeneous geometries, giving path lengths of approximate to 20 - 60 km and approximate to 10 - 30 km, respectively, under quiescent conditions. However path lengths derived during flaring are approximate to 2 - 3 times larger. These values are in excellent agreement with both estimates of the small-scale structure observed in the solar transition region, and path lengths derived previously for several other active late-type stars.