Phase separation in equiatomic AlCoCrFeNi high-entropy alloy.

The microstructure of the as-cast AlCoCrFeNi high entropy alloy has been investigated by transmission electron microscopy and atom probe tomography. The alloy shows a very pronounced microstructure with clearly distinguishable dendrites and interdendrites. In both regions a separation into an Al-Ni rich matrix and Cr-Fe-rich precipitates can be observed. Moreover, fluctuations of single elements within the Cr-Fe rich phase have been singled out by three dimensional atom probe measurements. The results of investigations are discussed in terms of spinodal decomposition of the alloying elements inside the Cr-Fe-rich precipitates.

Reduced liver apoptosis after venous systemic oxygen persufflation in non-heart-beating donors.

Graft injury caused by warm ischemia in livers from non-heart-beating donors (NHBDs) strongly affects posttransplantation outcome and is associated with liver apoptosis, which is mediated by death receptors, such as Fas, a surface receptor of the tumor necrosis factor (TNF)-alpha family. The aim of this study was to test the ability of venous systemic oxygen persufflation (VSOP) to reduce apoptotic changes and Fas activation in the liver after warm ischemic insult in vivo. Livers of male Wistar rats were harvested 30 min after cardiac arrest from non-heart-beating donors (NHBD) with (NHBD + O2) or without (NHBD) application of gaseous oxygen during the cold storage period via the suprahepatic caval vein. After 24 h of storage in University of Wisconsin solution at 4 degrees C, viability of the livers was assessed upon isolated reperfusion in vitro. Conventional signs of tissue damage like enzyme release and bile production showed a significantly elevated nonspecific cell injury in the NHBD group. TUNEL staining revealed increased DNA fragmentation of sinusoidal endothelial cells in the NHBD group and more apoptotic hepatocytes than in the control group. All these alterations could be almost abrogated by the use of VSOP in the NHBD + O2 group. The immunohistochemical staining of Fas antigen expression showed a significantly elevated Fas receptor expression in the NHBD and NHBD + O2 groups, in accord with an eightfold increase of Fas receptor mRNA detected by real-time reverse-transcription polymerase chain reaction (RT-PCR). These results demonstrate that the postischemic apoptotic rate of sinusoidal endothelial cells in NHBD livers can be reduced by the use of VSOP. A significant improvement in liver integrity and viability was obtained with this technique, without influencing the expression of Fas expression.

[Postoperative and bacterial osteitis. New possibilities for therapy]. / Postoperative und bakterielle Osteitis. Neue Therapieansätze.

Current therapy concepts for post-trauma osteitis include radical debridement, stabilization of bone and soft tissue care using early flap transfers. With this more radical approach, the long term results are improved, however, total treatment time still is very long. In addition to the physical, mental and social consequences for the patient, treatment costs are also very high. Antibiotic therapy as an adjuvant is still standard and effective although the development of worldwide antibiotic resistance has increased treatment difficulties. One of the main aims of research is to reduce these problems or to prevent the development of osteitis entirely. However, research has not yet elucidated the complex immunologic changes involved. In addition, most results are obtained from animal studies and clinical investigations are required.

Evidence for persistence of parvovirus B19 DNA in livers of adults.

Recent studies have suggested a pathogenic role of human parvovirus B19 (B19) in the development of acute fulminant liver failure in children. The hypothesis was based on the detection of B19 DNA in 8 of 10 explanted livers of children requiring liver transplantation. In the present study, explanted livers from 43 adults selected at random undergoing orthotopic liver transplantation for various reasons were examined. Pre-transplant sera were available from 40 patients of whom 35 (88%) were anti-B19 IgG-seropositive. All but one serum were negative for anti-B19 IgM antibody. By polymerase chain reaction, B19 DNA was detected in the livers of 15/35 (43%) anti-B19 IgG-positive patients, in 2/3 livers of patients with unknown anti-B19 antibody status, and in the initial transplant of an anti-B19 IgG-positive patient who underwent liver retransplantation, and whose own liver was negative for B19 DNA. In a second study group, liver and bone marrow samples from 23 autopsied adults selected at random were tested. Serum specimens were available from 22 individuals, of whom 17 (77%) were anti-B19 IgG-seropositive. All sera were negative for anti-B19 IgM antibody. B19 DNA was detected in the livers of 4/17 (24%) anti-B19 IgG-positive individuals, three of whom had also B19 DNA in their bone marrow. This is the first report demonstrating that B19 DNA is frequently present in livers of anti-B19 seropositive adults suggesting persistence of B19 in the liver. Further studies are needed to address whether B19 is an innocent bystander in the liver or whether the presence of B19 in liver is of biological and clinical significance.

Fas receptor is upregulated in livers from non-heart-beating donors.

Cell injury in livers from non-heart-beating donors (NHBDs) is not only caused by necrosis, but it is increasingly being recognized that apoptotic transformation contributes to postischemic cell death. It remains unclear which pathways lead to apoptosis. We suggested that apoptosis in NHBD livers might be mediated by the Fas receptor. Therefore the aim of our study was the detection and quantification of the Fas receptor, Fas mRNA and apoptosis in NHBD livers. Livers of male Wistar rats were harvested either from heart-beating donors (control, n = 15) or 30 min after cardiac arrest from NHBDs (n = 15). All livers were stored in University of Wisconsin solution for 24 h at 4 degrees C, and reperfused using a recirculating model with oxygenated Krebs-Henseleit buffer for 120 min at 37 degrees C. Conventional signs of cell damage, such as enzyme release and bile production, showed an elevated nonspecific cell injury in NHBD livers. The immunohistochemical staining of Fas antigen expression revealed a 7% rate of Fas receptor-expressing hepatocytes in the control group, but a considerable increase up to 38% in the NHBD group. No Fas antigen expression was detected on sinusoidal endothelial cells. Real-time RT-PCR detected an approximately eightfold elevated concentration of Fas mRNA transcripts in NHBD livers. We conclude that upregulation of the Fas receptor on hepatocytes in NHBDs will prime these cells to eventually undergo apoptosis upon reperfusion in vivo. Therefore, therapeutic modulation of the Fas pathway must be considered as a new strategy in order to additionally protect NHBD livers which are otherwise prone to parenchymal apoptosis.

Experimental liver preservation with Celsior: a novel alternative to University of Wisconsin and histidine-tryptophan-alpha-ketoglutarate solutions?

Celsior, a low viscosity and low potassium preservation solution, has recently been tested successfully in the cold preservation of heart, lung, kidney and small intestine. The purpose of the present study was to evaluate the potential of Celsior in the cold preservation of the liver. Livers were harvested from male Wistar rats and then flushed with either Celsior (CE), University of Wisconsin solution (UW) or histidine-tryptophan-alpha-ketoglutarate solution (HTK) and stored for 24 h at 4 degrees C in the respective solution. The reperfusion was performed in vitro using a recirculating model with oxygenated (95% O(2), 5% CO(2)) Krebs-Henseleit buffer at 37 degrees C. To simulate the slow rewarming during the surgical implantation in vivo, all livers were stored for 30 min at room temperature prior to reperfusion. After ischemic storage and also after reperfusion some samples were freeze-clamped for analysis of tissue metabolites while others were tested for structural and functional integrity by the isolated perfusion. CE vs. UW vs. HTK: Metabolic preservation of tissue ATP (micromol/g dry weight) during cold storage was best with Celsior (0. 46 +/- 0.17 vs. 0.26 +/- 0.03 vs. 0.35 +/- 0.07; p < 0.05 CE vs. UW), but upon reperfusion energetic recovery was comparable in the three groups (3.45 +/- 0.66 vs. 4.27 +/- 0.41 vs. 3.63 +/- 0.64 micromol/g/dry weight). There appeared to be structural integrity during reoxygenation irrespective of the used preservation solution with comparable values of parenchymal enzyme release (ALT: 575 +/- 82 vs. 547 +/- 106 vs. 593 +/- 38 mU/g/l), bile production (18.0 +/- 1.0 vs. 18.5 +/- 2.5 vs. 18.7 +/- 1.4 microl/g/ min), and the release of acid phosphatase, an indicator for activated Kupffer cells (89 +/- 13 vs. 90 +/- 5 vs. 123 +/- 21 mU/g/l) in this in vitro model. Vascular flow characteristics were approximated by the portal perfusion pressure, which tended to be elevated upon initial reperfusion in the UW group (8.4 +/- 0.6 mm Hg) compared to 6.6 +/- 1.0 and 7.3 +/- 0.4 mm Hg in Celsior and HTK, respectively. However, the pressure values decreased to the normal range even in the UW group with ongoing perfusion. The sensitivity of our model in detecting protective effects of the tested solution was confirmed by a negative control group of livers stored in Ringer's solution at 4 degrees C, yielding an impaired recovery which differed by one magnitude from the three other groups. Within the limits of an in vitro study it is concluded from these results that Celsior may become a suitable alternative for liver preservation and further studies including a transplantation in vivo are strongly encouraged.