0000000000261425
AUTHOR
Stefan Fischer
Lung Preservation With Perfadex or Celsior in Clinical Transplantation: A Retrospective Single-Center Analysis of Outcomes.
BACKGROUND Despite improvement of lung preservation by the introduction of low-potassium dextran (LPD) solution, ischemia-reperfusion injury remains a major contributor to early post-lung transplant graft dysfunction and mortality. After favorable experimental data, Celsior solution was used in our clinical lung transplant program. Data were compared with our historic LPD cohort. METHODS Between January 2002 and January 2005, 209 consecutive lung transplantations were performed with LPD. These were compared to 208 transplants between February 2005 and September 2007 with Celsior. Endpoints included posttransplant PaO2/FiO2 ratio at different timepoints after intensive care unit (ICU) admiss…
Design, synthesis, and biological evaluation of novel disubstituted dibenzosuberones as highly potent and selective inhibitors of p38 mitogen activated protein kinase.
Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical properties as well as potency. Extremely potent inhibitors were obtained, with half-maximal inhibitory concentration (IC(50)) values in the low nM range in a whole blood assay measuring the inhibition of cytokine release. The high potency of the target compounds together with the outstanding selectivity of this novel class of compounds toward p38 mitogen activated protein (MAP) kin…
Magnetic separation of encapsulated islet cells labeled with superparamagnetic iron oxide nano particles.
Islet cell transplantation is a promising option for the restoration of normal glucose homeostasis in patients with type 1 diabetes. Because graft volume is a crucial issue in islet transplantations for patients with diabetes, we evaluated a new method for increasing functional tissue yield in xenogeneic grafts of encapsulated islets. Islets were labeled with three different superparamagnetic iron oxide nano particles (SPIONs; dextran-coated SPION, siloxane-coated SPION, and heparin-coated SPION). Magnetic separation was performed to separate encapsulated islets from the empty capsules, and cell viability and function were tested. Islets labeled with 1000 μg Fe/ml dextran-coated SPIONs expe…
The hydrolysis of 6-phosphogluconolactone in the second step of pentose phosphate pathway occurs via a two-water mechanism.
Hydrolysis reaction marks the basis of life yet the mechanism of this crucial biochemical reaction is not completely understood. We recently reported the mechanisms of hydrolysis of nucleoside triphosphate and phosphate monoester. These two reactions hydrolyze P-O-P and P-O-C linkages, respectively. Here, we present the mechanism of hydrolysis of δ-6-phosphogluconolactone, which is an important precursor in the second step of the pentose phosphate pathway. Its hydrolysis requires the cleavage of C-O-C linkage and its mechanism is hitherto unknown. We report three mechanisms of hydrolysis of δ-6-phosphogluconolactone based on density functional computations. In the energetically most favorab…
Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment.
Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), …
Retrograde in situ versus antegrade pulmonary preservation in clinical lung transplantation: a single-centre experience.
OBJECTIVE Experimental and clinical studies have indicated a beneficial effect of retrograde lung preservation on post-transplant results. Accordingly, we conducted a non-randomized trial. METHODS A total of 209 consecutive recipients transplanted with low-potassium dextrane (LPD)-preserved lungs were eligible for analysis. Antegrade lung preservation (AP) was performed in 173 patients and retrograde in situ perfusion (RP) in 36 patients using low-potassium dextrane solution in all cases. The prostacycline was added to preservation solution. RESULTS The main donor, graft and recipient characteristics did not differ significantly between groups. There was a beneficial trend toward improved o…