Alexandra Wagner

University of Tübingen

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Ana M. Azevedo

University of Lisbon

Dirk Freudenstein

Klinikum Ludwigsburg

Frank Duffner

University of Tübingen

M. Raquel Aires‐Barros

Institute for Biotechnology and Bioengineering

L Poulsgård

Copenhagen University Hospital

A.C. Dias-Cabral

University of Beira Interior

Ana M. Ferraria

University of Lisbon

Sara Sousa Rosa

University College London

Fabio Fait

Reutlingen University

Richard C. Willson

University of Houston

Cooperative Institutions

University of Lisbon

Institute for Biotechnology and Bioengineering

University of Tübingen

Instituto Politécnico de Lisboa

Instituto Superior Técnico

Universitätsklinikum Tübingen

Instituto de Biologia Experimental e Tecnológica

University Children's Hospital Tübingen

Copenhagen University Hospital

Rigshospitalet

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Mobile‐Phase Modulators as Salt Tolerance Enhancers in Phenylboronate Chromatography: Thermodynamic Evaluation of the Mechanisms Underlying the Adsorption of Monoclonal Antibodies

Biotechnology Journal (2019)

Sara A.S.L. Rosa Alexandra Wagner Cláudia L. da Silva M. Raquel Aires‐Barros Ana M. Azevedo

Phenylboronate chromatography has been employed for bioseparation applications though details concerning the mechanisms of interaction between the ligand and macromolecules remain widely unknown. Here, the phenomena underlying the adsorption of an anti‐human interleukin‐8 (anti‐IL8) monoclonal antibody (mAb) onto an m ‐aminophenylboronic acid ( m ‐APBA) ligand in the presence of different mobile‐phase modulators (NaF/MgCl 2 /(NH 4 ) 2 SO 4 ) and under different pH values (7.5/8.5/9.0) is investigated. Flow microcalorimetry (FMC) is applied to measure instantaneous heat energy transfer, providing insights about the role of specific and nonspecific interactions involved in the adsorptive process. Results show that the adsorption of anti‐IL8 mAb to m ‐APBA is enthalpically driven, corroborating the presence of the reversible esterification reaction between boronic acid or boronates and cis ‐diol‐containing molecules. Nevertheless, for all mobile‐phase modulators studied, changes in thermogram profiles are observed as well as reductions in the net heat of adsorption when increasing the pH. Overall, FMC and parallel chromatographic experiments data suggest that ligand salt tolerance could be enhanced using mobile‐phase modulators, with all salts studied promoting the specific cis ‐diol interactions and reducing nonspecific interactions. The last feature is more noticeable at pH values above ligand's p K a , mainly due to the ability of NaF and (NH 4 ) 2 SO 4 to diminish electrostatic interactions when compared to the commonly used NaCl.

Boronic acid

Isothermal microcalorimetry

10.1002/biot.201800586

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Citations (1)

Subdural Hygroma as a Complication of Endoscopic Neurosurgery. Two Case Reports.

Neurologia medico-chirurgica (2002)

Dirk Freudenstein Alexandra Wagner Ulrike Ernemann Frank Duffner

Two cases of subdural hygroma occurred in a series of 77 neuroendoscopic procedures. An 8-year-old boy underwent neuroendoscopic cysto-cisternostomy of a left temporal arachnoid cyst. Routine postoperative magnetic resonance imaging 7 days later showed a large left-sided subdural hygroma without clinical symptoms. During the following 3 months, the subdural hygroma did not resolve spontaneously, so it was drained through a burr hole. A 3-month-old boy with aqueductal stenosis developed bilateral subdural hygromas after third ventriculostomy. Several punctures through the open anterior fontanelle relieved the hygromas but increasing head circumference required ventriculoperitoneal shunting 12 months later. Complications of neuroendoscopic procedures are increasingly reported, including various kinds of bleeding, infections, or damage of neuronal tissue. Only three previous cases of subdural hygroma or hematoma after neuroendoscopic interventions have been reported. The possible etiologies and clinical consequences of this rare complication have to be considered before selecting neuroendoscopy treatment.

Cystic hygroma

Shunting

Subdural haematoma

Arachnoid cyst

10.2176/nmc.42.554

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Citations (30)

[Endoscopic closure of cranionasal cerebrospinal fluid fistulas with the use of neuronavigation--"Computer Aided Surgery"].

PubMed (2001)

Michael Kosteljanetz Christian von Buchwald L Poulsgård Niels Rasmussen Alexandra Wagner

Conventionally, cranionasal cerebrospinal fluid (CSF) fistulas have been closed by repair of the dural defect via an open craniotomy. These techniques may be cumbersome, not without complications, and far from successful. In recent years, endoscopic techniques have been developed in the field of nasal surgery and neurosurgery. Furthermore, by means of computer-aided surgery or neuronavigation, it is possible to identify the surgical track with a high degree of accuracy and, by the same token, identify the defect in the cranium.By combining the endoscopic technique with computer-aided surgery, we have operated on six patients with cranionasal CSF fistulas endonasally. The fistula was confirmed before surgery by subaracnoidal injection of fluorescein.The surgery was successful and without any complications in all six cases.The method is recommended as the operation of first choice for cranionasal CFS fistulas, as compared to transcranial surgery. It is probably more efficient and with fewer complications than conventional surgery. A collaboration between neurosurgeons and ENT surgeons, like ours, can be recommended.

Neuronavigation

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Citations (4)

Screening polymeric ionic liquids for chromatography-based purification of bacteriophage M13

Separation and Purification Technology (2020)

Maria João Jacinto Alexandra Wagner Inês M. Sá David J.S. Patinha Isabel M. Marrucho

Ion chromatography

Biomolecule

Matrix (chemical analysis)

10.1016/j.seppur.2020.117906

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Citations (3)

Purification of monoclonal antibodies in a stirred cell with polyethyleneimine‐modified polyethersulfone ultrafiltration membrane

Journal of Chemical Technology & Biotechnology (2019)

Alexandra Wagner Ana M. Ferraria A.M. Botelho do Rego Marı́lia Mateus Ana M. Azevedo

Abstract BACKGROUND Charged ultrafiltration membranes combined with optimal operating conditions can be used to enable monoclonal antibody purification. Positively charged ligands bound to the membrane surface can significantly contribute to the adsorption of negatively charged proteins and enhance the purification process. RESULTS In this work, commercially available 500 kDa polyethersulfone ultrafiltration membranes were modified by sulfonation, followed by deposition of polyethyleneimine (PEI) and crosslinking with butanedioldiglycidylether. Polymer molecules of 2 and 10 kDa were used to evaluate how polymer size influences the fractionation of a harvested Chinese hamster ovary cell culture fluid containing a monoclonal antibody by ultrafiltration at different operational pH values. The precursor and modified membranes were analyzed by X‐ray photoelectron spectroscopy, which confirmed the successful modification of membranes. Nitrogen analysis showed the presence of amine groups, clearly confirming immobilization of PEI onto the membrane surface. When 10 kDa PEI is chosen for membrane modification, the intensity of this signal increases, as predicted for a higher‐molecular‐weight polymer. Ultrafiltration performance indicators (fluxes, transmissions, yields) were determined and compared for the modified and precursor membranes, with the PEI‐derived membranes showing ability for pH modulation of selectivity. CONCLUSION High purities were consistently observed at pH 9 owing to a simultaneous decrease in the transmission of soluble protein and increase in both IgG transmission and adsorptive capacity of the membranes. A single‐step process at pH 9 renders a permeate with an antibody purity of 96%, using a non‐crosslinked membrane modified with 10 kDa PEI. © 2019 Society of Chemical Industry

Ultrafiltration (renal)

10.1002/jctb.6157

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Citations (7)

Possible Mechanisms for Rapid Spontaneous Resolution of Acute Epidural Hematomas

Clinical Neuroradiology (2002)

Alexandra Wagner Dirk Freudenstein Sigrid Friese Frank Duffner

Subdural Hematomas

Conservative Treatment

Posterior fossa

10.1007/s00062-002-2327-9

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Citations (8)

Simultaneous virtual representation of both vascular and neural tissue within the subarachnoid space of the basal cistern--technical note.

PubMed (2002)

Dirk Freudenstein Alexandra Wagner Özlem Gürvit Dirk Bartz Frank Duffner

The representation of different anatomical structures requires varying imaging modalities and protocols. By mental composition of single-slice images, a three-dimensional (3D) impression can be achieved. However, this presupposes an outstanding imagination and is subject to inaccuracies. The use of an interactive and multi-modal planning system which represents different data sets in one single virtual environment holds promise to facilitate and improve neurosurgical decision-making. The authors report the clinical application of a self-developed virtual planning system in a case of trigeminal neuralgia due to an ectatic basilar artery.We modified our virtual planning system (VIVENDI), to achieve a virtual representation of the basal cistern illustrating both vascular and neuronal information. After conducting several experiments to determine an appropriate scanning protocol, we matched the data achieved by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA).The system provides the vascular topography combined with information on the anatomical structure of the subarachnoid space. To illustrate the clinical usefulness of this planning approach, the authors present a case of trigeminal neuralgia caused by an ectatic basilar artery. Pre-operatively, the virtual representation returned accurate information on the anatomical configuration of the cerebellopontine angle and the course of the ectatic vessel. This information was confirmed during surgery.The presented case demonstrates the clinical applicability of VIVENDI within the subarachnoid space of the basal cistern. The virtual representation enables pre-operative planning and simulation based on the patient's individual anatomy.

Subarachnoid space

Representation

Cistern

Surgical Planning

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Citations (4)

Rational Design of Pore Parameters in Monodisperse Porous Poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) Particles Based on Response Surface Methodology

Polymers (2022)

Julia C. Steinbach Fabio Fait Stefanie Wagner Alexandra Wagner Marc Brecht

Monodisperse porous poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) particles are widely applied in different fields, as their pore properties can be influenced and functionalization of the epoxy group is versatile. However, the adjustment of parameters which control morphology and pore properties such as pore volume, pore size and specific surface area is scarcely available. In this work, the effects of the process factors monomer:porogen ratio, GMA:EDMA ratio and composition of the porogen mixture on the response variables pore volume, pore size and specific surface area are investigated using a face centered central composite design. Non-linear effects of the process factors and second order interaction effects between them were identified. Despite the complex interplay of the process factors, targeted control of the pore properties was possible. For each response a response surface model was derived with high predictive power (all R2predicted > 0.85). All models were tested by four external validation experiments and their validity and predictive power was demonstrated.

Glycidyl methacrylate

Ethylene glycol dimethacrylate

Dispersity

Surface Modification

10.3390/polym14030382

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Citations (6)

Primary Purification of Plasmid DNA Using Differential Isopropanol Precipitation

Methods in molecular biology (2020)

Alexandra Wagner A. Rita Silva-Santos Sara Sousa Rosa Sophie Gierak Ana M. Azevedo

10.1007/978-1-0716-0872-2_8

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Citations (1)

Neuroendoscopic Treatment of Idiopathic Occlusion of the Foramen of Monro in Adults. Two Case Reports.

Neurologia medico-chirurgica (2002)

Dirk Freudenstein Frank Duffner Hilmar Krapf Alexandra Wagner E. H. Grote

Two adults presented with hydrocephalus due to idiopathic obstruction of the bilateral foramina of Monro, manifesting as clinical signs of chronically elevated intracranial pressure. No inflammation was present. The primary surgical treatment was neuroendoscopic reconstruction of the right foramen of Monro. A 37-year-old man had a spontaneous perforation of the septum pellucidum. The patient required a ventriculoperitoneal shunt, although postoperative ventriculography proved free passage of cerebrospinal fluid from the lateral ventricle into the third ventricle. A 62-year-old man underwent additional septostomy and third ventriculostomy, and the neuroendoscopic intervention relieved the presenting symptoms without additional treatment. The biopsy specimens showed no evidence of malignancy in either case. Neuroendoscopic intervention is an alternative treatment in the management of hydrocephalus due to idiopathic obstruction of the foramen of Monro. The procedure is less invasive than open microsurgical reconstruction and can even avoid ventriculoperitoneal or ventriculoatrial shunting.

Foramen

10.2176/nmc.42.81

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Citations (25)