Publications by authors named "Metzner H"

We propose a revision of the spider genus Corythalia C.L. Koch, 1850 (Salticidae: Euophryini) with a revised genus diagnosis based on examination of all species available to us.

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Unlabelled: Essentials AFSTYLA exhibits ≈50% underestimation in activity when the one-stage (OS) assay is utilized. A field study compared the performance of AFSTYLA with Advate in factor VIII activity assays. AFSTYLA activity can be monitored with both the chromogenic substrate and the OS assay.

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Aging causes major alterations of all components of the neurovascular unit and compromises brain blood supply. Here, we tested how aging affects vascular reactivity in basilar arteries from young (<10 weeks; y-BA), old (>22 months; o-BA) and old (>22 months) heterozygous MYPT1-T-696A/+ knock-in mice. In isometrically mounted o-BA, media thickness was increased by ∼10% while the passive length tension relations were not altered.

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rVIII-SingleChain is a novel recombinant single-chain factor VIII (FVIII) construct, comprising covalently bonded heavy and light chains. Post-translational modifications of FVIII affect physicochemical parameters, including hydrophobicity and charge. The most relevant post-translational modifications of FVIII products are N-glycosylation of asparagine residues and tyrosine sulphations.

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Introduction: rVIII-SingleChain (CSL627), a novel recombinant coagulation factor VIII (FVIII), is under investigation in a phase I/III clinical programme (AFFINITY) for the treatment of haemophilia A. Non-clinical studies were conducted to investigate the pharmacokinetic/pharmacodynamic profile of rVIII-SingleChain in comparison with full-length recombinant FVIII.

Materials And Methods: Binding affinity of rVIII-SingleChain for von Willebrand factor was investigated by surface plasmon resonance analysis.

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The prophylactic treatment of haemophilia B and the management of haemophilia A or B with inhibitors demand frequent administrations of coagulation factors due to the suboptimal half-lives of the products commercially available and currently in use, e.g. recombinant factor IX (rFIX) and recombinant factor VIIa (rFVIIa), respectively.

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Introduction: The preclinical efficacy and safety of rVIII-SingleChain (CSL627), a novel recombinant single-chain factor VIII, was assessed in a series of animal studies.

Materials And Methods: In the tail-clip bleeding model, hemophilia A mice were injected with escalating doses (1-150 IU/kg) of rVIII-SingleChain, B-domain deleted (BDD) rFVIII (ReFacto AF(®)), or full-length rFVIII products (Advate(®), Helixate(®)). Total blood loss and the percentage of animals in which hemostasis occurred were assessed in this observer-blinded, randomized study.

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We observe variable-range hopping conduction in thermal admittance spectroscopy and develop a method to evaluate the signal under this condition. As a relevant example of demonstration we employ Cu(In,Ga)(Se,S)2 thin-film solar cells and show that the fundamental N1 signal, which has been discussed for more than a decade in terms of minority carrier traps, does not display trap parameters, but is generated by the freezing-out of carrier mobility with decreasing temperature when hopping conduction prevails. This effect offers a new approach to carrier hopping and to semiconductors suffering from small mobility.

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Haemophilia B is a X-chromosome linked disease characterised by a deficiency of functionally active coagulation Factor IX (FIX). Patients with severe haemophilia B at risk of recurrent bleeding are treated approximately twice a week in a prophylactic setting by application of FIX concentrates. To increase convenience and compliance of the therapy it is desirable to reduce the dosing frequency by improving the pharmacokinetic properties of FIX.

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Background: Thrombelastography has received renewed interest in the perioperative setting. The main determinants of thrombelastographic results are coagulation factor concentrations (various zymogens and fibrinogen) and platelet count; thus, platelet inhibition renders these assays mainly coagulation factor dependent. Assays with and without platelet inhibition are thus increasingly used to trigger and monitor replacement therapy with blood products.

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Open channel block is a process in which ions bound to the inside of a channel pore block the flow of ions through that channel. Repulsion of the blocking ions by depolarization is a known mechanism of open channel block removal. For the NMDA channel, this mechanism is necessary for channel activation and is involved in neuronal plasticity.

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von Willebrand disease (vWD) is a bleeding disorder that results from defects in the quality or quantity of von Willebrand factor (vWF), a glycoprotein essential for normal thrombus formation. vWF circulates in plasma as multimers in sizes ranging up to 20,000 kd. The high molecular weight vWF (HMWvWF) multimers are most essential for primary hemostasis, whereas the lower molecular weight multimers are less functionally active.

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Introduction: Fibrin sealants (FS) have been used for many years to facilitate hemostasis and to provide suture support and sealing/adhesion of tissues after surgery. While their composition is similar, different formulations, application devices, and varying concentrations of key components mean that the properties of clots formed by individual FS can be diverse.

Materials And Methods: We performed several studies, including animal models, to compare the properties of 12 different commercially available FS/application device combinations using partial liver and kidney resection models to assess hemostatic efficacy and a novel pig skin model to measure adhesive clot strength.

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Factor XIII has a well-established role in natural coagulation and clot stabilization. It is often added back to fibrin sealants that are used in a wide range of surgical settings to achieve successful hemostasis, tissue adhesion and wound healing. Factor XIII is the final enzyme to be activated in the blood coagulation cascade.

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Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice.

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Background: The need for factor XIII (FXIII) in fibrin sealant is subject to discussions. Some commercially available fibrin sealants (FS) contain high levels of FXIII (up to 70-80 U/mL) while others contain low levels or none. The objective of the present studies was to investigate the need for FXIII in FS.

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Background: Recent progress in the cardiotypic differentiation of embryonic and somatic stem cells opens novel prospects for the treatment of cardiovascular disorders. The aim of the present study was to develop a novel surgical approach that allows standardized cellular cardiomyoplasty in mouse with low-perioperative mortality.

Methods: Reproducible transmural lesions were generated by cryoinjury followed by intramural injection of embryonic cardiomyocytes using a newly designed holding device and vital dye staining.

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Background: Suture hole bleeding is a frequent complication in vascular surgery. The use of fibrin sealants (FSs) during surgery is reported to reduce blood loss by enhancing hemostasis.

Objectives: Using a pig vascular graft model we investigated: (1) the use of FSs in vascular surgery and measured blood loss with and without the use of FSs; (2) the effect of factor XIII in FSs on hemostasis and blood loss; and (3) the effect of increasing FS incubation time on hemostasis and blood loss.

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Article Synopsis
  • The study investigated the effects of factor XIII on the barrier function of endothelial cells using cultured porcine aortic endothelial cells and rat heart models.
  • Activated factor XIII significantly decreased albumin permeability of endothelial monolayers by about 30% within 20 minutes, while nonactivated factor XIII showed no change.
  • The protective action of activated factor XIII was linked to the preservation of endothelial barrier function during energy depletion, likely through changes in the paracellular pathways between endothelial cells.
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In order to provide patients with von Willebrand disease a factor VIII (FVIII)/von Willebrand factor (vWF) concentrate of reproducible quality, an SDS-agarose gel electrophoresis method has been established to determine the content of the high molecular weight multimers (band 11 and higher) of vWF. This method has been used to characterize the content of high molecular weight vWF multimers in Humate P/Haemate P, a commercial FVIII/vWF concentrate. The average content of high molecular weight vWF multimers of 47 batches of Humate P/Haemate P has been determined to be 84.

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The structure of recombinant human cellular factor XIII zymogen was solved in its monoclinic crystal form and refined to an R-factor of 18.3% (Rfree = 23.6%) for all data between 40.

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The production of recombinant glycoprotein therapeutics requires characterization of glycosylation with respect to the lot-to-lot consistency. Here we introduce the ¿hypothetical N-glycan charge Z' as a parameter that allows to characterize the protein glycosylation in a simple, however, efficient manner. The hypothetical N-glycan charge of a given glycoprotein is deduced from the N-glycan mapping profile obtained via HPAE-PAD.

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With the increasing availability of human plasma this source was used to substitute for the production of factor XIII concentrate from placenta. Prior to changing the source material, the virus safety in accordance with the Committee for Proprietary Medicinal Products (CPMP) guidelines and the half-life were investigated. Concerning the virus safety, the following cumulative log 10 clearance factors were obtained: human immunodeficiency virus (HIV) > or = 18.

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