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Alf Theisen

Publications and source records attributed to Alf Theisen.

4 recordsLinked to original sources

Influence of surfactants, polymer and doxorubicin loading on the anti-tumour effect of poly(butyl cyanoacrylate) nanoparticles in a rat glioma model.

Poly(n-butyl cyanoacrylate) nanoparticles coated with polysorbate-80 can enable the transport of bound drugs across the blood-brain barrier (BBB) after i.v. injection. In the present study the influence of different formulation parameters on the anti-tumoural effects of doxorubicin nanoparticles against glioblastoma 101/8 was investigated. The manufacturing parameters of poly(alkyl cyanoacrylate) doxorubicin-loaded nanoparticles were optimized concerning drug loading. The nanoparticles were coated with different surfactants and injected intravenously on days 2, 5 and 8 after intra-cranial implantation of glioblastoma 101/8 to rats. The survival times of all doxorubicin containing preparations, including a doxorubicin solution, increased the survival times significantly compared to untreated tumour-bearing rats. The most pronounced increase in survival was obtained with the poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles coated with polysorbate 80 and 35% of these animals survived for over 180 days (termination of the experiments). The other nanoparticle preparations yielded lower survival times. Poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles coated with polysorbate 80-coated proved to be very efficient against glioblastoma 101/8. The data suggest that the interaction of nanoparticles with the blood after injection as well as the enhanced permeability and retention effect (EPR effect) contributed differently to the anti-tumoural efficacy depending on nanoparticle formulation and surface properties.

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A novel dynamic model for experimental spinal cord compression.

OBJECT: The goal of this study was to develop a novel dynamic model for experimental spinal cord compression that closely approximates neoplastic epidural compression of the spinal cord in humans. METHODS: In 30 New Zealand white rabbits, the thoracic spine was exposed via a posterior approach. On each side of one vertebral lamina a small hole was drilled caudal to the articular process. A silicone band was passed through these holes, forming a loop. The spinal dura mater was exposed via an interlaminar approach. The loop was brought into contact with the dura mater and fixed in its position encircling 270 degrees of the circumference of the spinal cord. Thereafter, the loop was gradually tightened at set times by pulling at the ends of the band and fixing them again in their new position. The spinal cord was thus increasingly compressed in a circular and dynamic manner. Neurological deficits of various degrees were created in all animals in the compression group, and the compressive effect of the loop was reliably demonstrated on MR imaging. After decompression of the spinal cord, the neurological deficits were reversible in the majority of animals, and MR imaging revealed either no signal changes or only circumscribed ones within the cord. In contrast, MR images obtained in animals that did not recover revealed the occurrence of extensive chronic myelopathy. CONCLUSIONS: This novel model features reproducibility of paresis and neurological recovery. It is a dynamic model simulating circular tumor growth and is characterized by its easy, straightforward, and cost-saving applicability.

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In vivo inhibition of neutrophil activity by a FAS (CD95) stimulating module: arterial in-line application in a porcine cardiac surgery model.

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass is associated with aberrant neutrophil activation and potentially severe pathogenic sequelae. This experimental study was done to evaluate a leukocyte inhibition module that rapidly inactivates neutrophils through CD95 stimulation. METHODS: German landrace pigs (4 groups, each n = 5) underwent cardiac surgery without cardiopulmonary bypass (group I), with cardiopulmonary bypass (group II), with cardiopulmonary bypass plus a leukocyte filter (group III), and with cardiopulmonary bypass plus a leukocyte inhibition module (group IV). The leukocyte filter or leukocyte inhibition module was introduced into the arterial line of the heart-lung machine. RESULTS: Leukocyte counts were decreased by up to 43% in group IV compared with values in group II (P =.023). In group IV, but not in groups I to III, no delay in spontaneous neutrophil apoptosis was observed after annexin V-propidium iodide staining. Late apoptotic (11.7%) or necrotic neutrophils (9.3%) were detected in 2 animals (group IV). Tumor necrosis factor alpha serum levels increased over time in groups I to III (>2-fold) but remained at baseline levels in group IV (P <.05). Interleukin 8-mediated chemotactic neutrophil transmigration activity increased over time in groups I to III but was totally abrogated in group IV at any time point. The perioperative increase of creatine kinase and creatine kinase MB levels was lower in groups III (1.5-fold and 1.3-fold, respectively) and IV (1.2-fold and 1.5-fold, respectively) compared with values in group II (both 1.9-fold). CONCLUSIONS: The leukocyte inhibition module downregulated cardiopulmonary bypass-related neutrophil activity and thus might be beneficial in cardiac surgery and other clinical settings with unappreciated neutrophil activation.

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Standardized qualitative evaluation of scar tissue properties in an animal wound healing model.

There is a great need to establish reproducible methods for evaluative studies of wound treatment and wound healing. Validation of the healing process through optical techniques, as well as histologic and immunohistochemical methodologies, have been improved and to some extent have become well-established assays. Data relating to biomechanical properties, e.g., evaluation of the tensile strength of scar tissue that forms in experimental wound treatment strategies, are less widely available. We chose the domestic pig as an animal model in which to examine epidermal wound healing. We implanted specially made chambers that served to isolate the wounds and prevent epidermal migration from the edges. We performed histologic and immunohistochemical analyses as well as evaluation of biomechanical qualities of scar tissue using laser tensiometry. Pig skin is well suited for wound healing studies, and wound creation, implantation of the chambers, and the regular changing of dressings could all be carried out in the operating theater. In addition to established macroscopic evaluation and microscopic documentation, the need for objective biomechanical assessment of scar tissue by measuring tensile strength has been met using laser tensiometry. By optimizing methods for measuring tensile strength, it is possible to evaluate the biomechanical quality of scar tissue formed following different courses of wound treatment, as well as histologic assessment.

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