Mediators of leukocyte yctivation play a role in disseminated intravascular coagulation during orthotopic liver transplantation

Leukocytes play an important role in the development of disseminated intravascular coagulation (DIC). In the reperfusion phase of OLT a DIC-like situation has been described and has been held responsible for the high blood loss during this phase. We investigated the role of leukocytes in the pathogenesis of DIC in OLT by measuring the leukocytic mediators released upon activation (cathepsin B, elastase, TNF, neopterin) and the levels of thrombin-antithrombin III (TAT) complexes, seen as markers of prothrombin activation. Arterial blood samples were taken at 10 different time points during and after OLT. Samples were also taken of the perfusate released from the liver graft vein during the flushing procedure before the reperfusion phase. Aprotinin was given as a continuous infusion (0.2-0.4 Mill. KlU/hr) and its plasma levels were determined. Significantly elevated levels of neopterin (15-fold; P<0.01), cathepsin B (440-fold; P<0.01) in the perfusate, as compared with the systemic circulation, as well as their significant increases in the early reperfusion phase suggested that they were released by the graft liver. This was paralleled by elevated levels of elastase (1.3-fold, P<0.05), TNF (1.5-fold, P=NS), and TAT complexes (1.4-fold; P<0.1) in the perfusate. Significant correlations could be identified between the parameters of leukocyte activation and TAT complexes, whereas no correlation was observed between any of the parameters investigated and the aprotinin levels. Our results strongly indicate a release of leukocytic mediators from the graft liver during its reperfusion which seems to be related to the parallely increased prothrombin activation. No correlation could be seen between levels of aprotinin and levels of leukocytic mediators

Different aprotinin applications influencing hemostatic chances in orthotopic liver transplantation

The effect of different aprotinin applications on hemmtatic changes and blood product requirements in orthotopic liver transplantation was investigated in a prospective, open, and randomized study. From November 1989 to June 1990, 13 patients received aprotinin as a bolus of 0.5 Mill, kallikrein inac-tivator units (KIU) on three occasions in the course of an OLT, whereas 10 other patients were treated with continuous aprotinin infusion of 0.1-0.4 Mill. KIU/hr. Before and after reperfusion of the graft liver, signs of hyperfibrinolysis, measured by thrombelastography, were significantly lower in the infusion group. Tissue-type plasminogen activator (t-PA) activity increased during the anhepatic phase but to a significantly lesser extent in the infusion group. Blood product requirements during OLT were tendentiously higher in the bolus group but not significantly so. However, the use of packed red blood cells was significantly lower in the postoperative period, whereas there was no significant difference in fresh frozen plasma requirements between the two groups. All 23 patients have survived, and only one woman of each group required retransplantation due to severe host-versus-graft reactions. Furthermore, we investigated the perfusate of the graft liver in both groups and detected signs of a decreased t-PA release in the infusion group. Our results demonstrate an advantage of aprotinin given as continuous infusion over bolus application in OLT

Melting of a Two-component Source beneath Iceland

New trace element and Hf-Nd isotope data on post-glacial basalts from Iceland's main rift zones are used in conjunction with literature data to evaluate the relative importance of source heterogeneity and the melting process for the final melt composition. Correlations between Hf and Nd isotope compositions and trace element ratios indicate that at least two source components are sampled systematically as a function of the degree and pressure of melting beneath Iceland. Strong depletion in Rb, Ba, U and Th and enrichment in Nb and Ta compared with La in the most enriched samples from the Reykjanes Peninsula and Western Rift Zone suggests that the enriched source component is similar to ancient recycled enriched mid-ocean ridge basalt (E-MORB) crust. Highly incompatible trace element ratios such as Nb/La and Nb/U and Pb isotope ratios are variable across Iceland. This observation suggests that either the enriched component is intrinsically heterogeneous, or that there is a larger proportion of the enriched source component beneath the Southwestern Rift Zone compared with the Northern Rift Zone. The relative effect of source heterogeneity and melting on the final melt composition was evaluated with a one-dimensional polybaric melt mixing model in which accumulated melts from a depleted MORB mantle and a recycled E-MORB crust are mixed in different ways. Two styles of melt mixing were simulated: (1) complete mixing of melts with variable proportions of the depleted mantle and recycled E-MORB components; (2) incomplete mixing with a fixed initial proportion of the two source components. Calculated pressure-dependent compositional changes using these simple two-component melting models can explain the observed trends in trace element ratio and isotope ratio diagrams for Icelandic basalts, even in cases where conventional binary mixing models would require more than two source components. The example of Iceland demonstrates that melt mixing during extraction from the mantle is a key process for controlling the trace element and isotope variability observed in basaltic lavas and must be evaluated before inferring the presence of multiple source component

Optimized signal deduction procedure for the MIEZE neutron spectroscopy technique

We report a method to determine the phase and amplitude of sinusoidally modulated event rates, binned into 4 bins per oscillation. The presented algorithm relies on a reconstruction of the unknown parameters. It omits a calculation intensive fitting procedure and avoids contrast reduction due to averaging effects. It allows the current data acquisition bottleneck to be relaxed by a factor of 4. Here, we explain the approach in detail and compare it to the established fitting procedures of time series having 4 and 16 time bins per oscillation. In addition we present the empirical estimates of the errors of the three methods and compare them to each other. We show that the reconstruction is unbiased, asymptotic, and efficient for estimating the phase. Reconstructing the contrast, which corresponds to the amplitude of the modulation, is roughly 10% less efficient than fitting 16 time binned oscillations. Finally, we give analytical equations to estimate the error for phase and contrast as a function of their initial values and counting statistics.Comment: 14 pages, 5 figures, submitted to IOP Measurement Science and Technolog

The self-assembly and evolution of homomeric protein complexes

We introduce a simple "patchy particle" model to study the thermodynamics and dynamics of self-assembly of homomeric protein complexes. Our calculations allow us to rationalize recent results for dihedral complexes. Namely, why evolution of such complexes naturally takes the system into a region of interaction space where (i) the evolutionarily newer interactions are weaker, (ii) subcomplexes involving the stronger interactions are observed to be thermodynamically stable on destabilization of the protein-protein interactions and (iii) the self-assembly dynamics are hierarchical with these same subcomplexes acting as kinetic intermediates.Comment: 4 pages, 4 figure