Publications (10)38.46 Total impact
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Article: The influence of retrograde reperfusion on the ischaemia-/reperfusion injury after liver transplantation in the rat.
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ABSTRACT: Dysfunction of the graft after liver transplantation caused by ischaemia-/reperfusion (I/R) injury is a serious clinical problem. The aim of this study was to evaluate the influence of different kinds of reperfusion on I/R injury in a rat model. Arterialized orthoptic rat liver treatment was performed on male LEWIS-(RT(1))-rats. Three groups (n = 7) were formed. Group I: antegrade reperfusion with a 6-min delayed reperfusion via the hepatic artery. Group II: Antegrade reperfusion, simultaneously, via the portal vein and the hepatic artery. Group III: Retrograde reperfusion via the vena cava. Serum parameters were determined one, 24 and 48 h after operation. Furthermore, after 48 h, the liver was taken for histological assessment. After 48 h, rats of group III showed significantly lower aspartate amino transferase and alanine amino transferase serum levels compared with group I and group II rats. Forty-eight hours after transplantation, glutamate dehydrogenase serum level was significantly lower in group III than in group II. In histology, group III livers showed significantly less necrotic spots than group I and group II livers. Maximum size of the necrotic spots was significantly lower in group III than in group I. Also, significantly more necrotic spots were seen in the 'Rappaport's zone' 1 and 2 of group I than in group III. Our data suggested that the expression of I/R-injury correlates with the type of reperfusion. Furthermore, under standard conditions, this study was able to demonstrate that in a rat model, the retrograde reperfusion leads to a lower expression of I/R-injury than the antegrade reperfusion.International Journal of Experimental Pathology 01/2009; 89(6):433-7. · 2.57 Impact Factor -
Article: Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial.
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ABSTRACT: Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have high recurrence rates. Immunostimulatory gene therapy is a promising approach in veterinary oncology. This phase I dose-escalation study was performed to determine toxicity and feasibility of gene therapy with feline granulocyte-macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas. Twenty cats were treated with plasmid coding for feGM-CSF attached to magnetic nanoparticles in doses of 50, 250, 750 and 1250 microg. Two preoperative intratumoral injections followed by magnetofection were given. Four control cats received only surgical treatment. Adverse events were recorded and correlated according to the veterinary co-operative oncology group toxicity scale. An enzyme-linked immunosorbent assay was performed to detect plasma feGM-CSF concentrations. No significant treatment related toxicity was observed. Preliminary recurrence results were encouraging as, on day 360, ten of 20 treated cats were recurrence-free. In conclusion, 1250 microg of feGM-CSF plasmid DNA applied by magnetofection is safe and feasible for phase II testing.The Journal of Gene Medicine 07/2008; 10(6):655-67. · 2.48 Impact Factor -
Article: GDNF-transduced Schwann cell grafts enhance regeneration of erectile nerves.
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ABSTRACT: Schwann cell-seeded guidance tubes have been shown to promote cavernous nerve regeneration, and the local delivery of neurotrophic factors may additionally enhance nerve regenerative capacity. The present study evaluates whether the transplantation of GDNF-overexpressing Schwann cells may enhance regeneration of bilaterally transected erectile nerves in rats. Silicon tubes seeded with either GDNF-overexpressing or GFP-expressing Schwann cells were implanted into the gaps between transected cavernous nerve endings. Six (10 study nerves) or 12 wk (20 study nerves) postoperatively, erectile function was evaluated by relaparotomy, electrical nerve stimulation, and intracavernous pressure recording, followed by ultrastructural evaluation of reconstructed nerves employing bright-field and electron microscopy. Additional animals were either sham-operated (positive control; 20 study nerves) or received bilateral nerve transection without nerve reconstruction (negative control; 20 study nerves). The combination of GDNF delivery and Schwann cell application promoted an intact erectile response in 90% (9 of 10) of grafted nerves after 6 wk and in 95% (19 of 20) after 12 wk, versus 50% (5 of 10) and 80% (16 of 20) of GFP-expressing Schwann cell grafts (p=0.02). The functional recovery was paralleled by enhanced axonal regeneration in GDNF-overexpressing Schwann cell grafts, as indicated by larger cross-sectional areas and a significantly higher percentage of neural tissue compared with GFP-transduced controls. These findings demonstrate that the time required to elicit functional recovery of erectile nerves can be reduced by local delivery of GDNF. In terms of clinical application, this enhanced nerve repair might be critical for timely reinnervation of the corpus cavernosum as a prerequisite for functional recovery in men.European Urology 03/2008; 54(5):1179-87. · 8.49 Impact Factor -
Article: In vivo analysis of retroviral gene transfer to chondrocytes within collagen scaffolds for the treatment of osteochondral defects.
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ABSTRACT: To examine a retroviral gene transfer to chondrocytes in vitro and in vivo in tissue-engineered cell-collagen constructs articular chondrocytes from rabbits and humans were isolated and transduced with VSV.G pseudotyped murine leukemia virus-derived retroviral vectors. Viral supernatants were generated by transient transfection of 293T cells using the pBullet retroviral vector carrying the nlslacZ gene, a Moloney murine leukemia virus gag/pol plasmid and a VSV.G coding plasmid. Transduction efficiency was analyzed by fluorescence-activated-cell-sorter analysis and transduced autologous chondrocytes from rabbits were seeded on collagen-scaffolds and implanted into osteochondral defects in the patellar groove of the rabbit's femur (n=10). LacZ-expression was analyzed by X-gal staining on total knee explants and histological sections. Retroviral transduction efficiency exceeded 92.3% (SEM+/-3.5%) in rabbit articular chondrocytes, 74.7% (SEM+/-1.8%) in human articular chondrocytes and 52.7% (SEM+/-5.8%) in osteoarthritic human chondrocytes. Reporter gene expression remained high after 15 weeks in 75.7% (SEM+/-8.2%) of transduced rabbit articular chondrocytes. In vivo, intraarticular beta-galactosidase activity could be determined in the majority of implanted chondrocytes in the osteochondral defects after 4 weeks.Biomaterials 11/2007; 28(30):4480-7. · 7.40 Impact Factor -
Article: 273. Immuno Gene Therapy of Feline Fibrosarcoma Using Intratumoral Magnetofection or Gene-Activated Matrices for Gene Delivery |[ndash]| Preliminary Results of a Veterinary Clinical Study
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ABSTRACT: Molecular Therapy (2006) 13, S105|[ndash]|S105; doi: 10.1016/j.ymthe.2006.08.327 273. Immuno Gene Therapy of Feline Fibrosarcoma Using Intratumoral Magnetofection or Gene-Activated Matrices for Gene Delivery |[ndash]| Preliminary Results of a Veterinary Clinical Study Ulrike Schillinger1, Bianca Schwarz2, Tina Kempf2, Anika Jahnke2, Cornelia Fischer2, Anne Loecher2, Stefanie Schlemmer2, Johannes Hirschberger2, Thomas Brill1, Roberto Koestlin1, Bernd Gaensbacher1 and Christian Plank11Institute of Experimental Oncology, Technical University, Munich, Munich, Germany2Department of Veterinary Internal Medicine, LMU Munich, Munich, GermanyMolecular Therapy 04/2006; · 6.87 Impact Factor -
Article: 573. Immuno Gene Therapy of Feline Fibrosarcoma Using Intratumoral Magnetofection for Gene Delivery – Preliminary Results of a Veterinary Clinical Study
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ABSTRACT: Molecular Therapy (2004) 9, S216–S216; doi: 10.1016/j.ymthe.2004.06.503 573. Immuno Gene Therapy of Feline Fibrosarcoma Using Intratumoral Magnetofection for Gene Delivery – Preliminary Results of a Veterinary Clinical Study Ulrike Schillinger1, Niels Kjaergaard2, Kathrin Wiedmann2, Anne Loecher2, Stefanie Schlemmer2, Bianca Schwarz1, Tina Kempf1, Johannes Hirschberger2, Roberto Koestlin3, Christian Plank1, Bernd Gansbacher1 and Thomas Brill11Institute of Experimental Oncology, Technical University Munich, Munich, Germany2Dept. of Veterinary Internal Medicine, Ludwig-Maximilian University, Munich, Germany3Dept. of Veterinary Surgery, Ludwig-Maximilian University, Munich, GermanyMolecular Therapy 04/2004; · 6.87 Impact Factor -
Article: Peri-implant care with the CO2 laser: In vitro and in vivo results
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ABSTRACT: Background: Numerous applications for dental lasers have been proposed for both clinical use and experimental purposes. A new indication might be the sterilization of exposed implant surfaces in order to rehabilitate ailing implants. The purposes of this study were to assess CO2 laser parameters for the decontamination process in vitro and to evaluate the method in vivo.Methods: In vitro, temperature changes at the bone–titanium implant interface were recorded during use of a CO2 laser-scanning system (Swiftlase®) and the effects of laser irradiation on titanium implants were examined. In vivo, in 6 beagle dogs, a total of 60 implants and bony defects were treated either conventionally by air-powder-abrasive or by laser irradiation or in combination to evaluate if reosseointegration can occur. In 16 patients (41 ailing implants), the reliability of the CO2 laser-assisted vs. conventional decontamination was tested.Results: Depending on the parameters chosen, melting and other surface alterations could be seen in vitro. In continuous wave mode, mean power output of 2.5 W for a maximum of 10 s is suitable for the decontamination process. In the beagle dog model, histologic examination revealed new direct bone-to-implant contact following laser-assisted therapy. The clinical study showed 4 months after therapy that laser-decontaminated implants and soft tissue resection resulted in statistically significant better radiographic parameters than conventional decontamination plus soft tissue resection.Conclusions: From these results it was concluded that treatment of peri-implantitis can be optimized using CO2 laser-assisted implant decontamination. Nevertheless, further studies are required in this field.ZusammenfassungEinleitung: In den letzten Jahren wurde eine zunehmende Zahl von Indikationen für den Einsatz von Dentallasern genannt. Eine neue Anwendung könnte in der Dekontamination freiliegender Implantatoberflächen bestehen. Ziel dieser Untersuchungen war, geeignete Laserparameter in vitro und in vivo zu identifizieren und die Methode am Patienten zu überprüfen.Material und Methode: In vitro wurden die Temperaturanstiege am Titan-Knochen-Interface während CO2 Laser-Bestrahlung unter Verwendung eines Scanners gemessen und die Auswirkungen auf die Implantatmorphologie untersucht. In einer tierexperimentellen Studie wurden insgesamt 60 periimplantäre Defekte konventionell, durch Laserbestrahlung bzw. in Kombination therapiert und histologisch untersucht, inwieweit knöcherne Reappositionen möglich sind. Ziel einer klinischen Studie an 16 Patienten bzw. 41 Implantaten war es, die Laser-gestützte Dekontamination im Vergleich zum konventionellen Vorgehen zu evaluieren.Ergebnisse: Abhängig von den Parametern waren Aufschmelzungen der Implantatoberfläche zu erkennen. Im cw-Betrieb waren dagegen mittlere Leistungen bis zu 2,5 W für bis zu 10 s Bestrahlungszeit applizierbar, ohne die kritische Temperatur am Interface zu überschreiten. Im Tiermodell zeigten sich nach 4 Monaten knöcherne Reappositionen an vormals kontaminierten Implantatoberflächen. In einer klinischen 3-Jahres-Studie waren nach Lasertherapie bessere röntgenologische Parameter nachweisbar als nach konventioneller Dekontamination.Konklusion: Aufgrund dieser Ergebnisse wurde die Schlussfolgerung gezogen, dass die CO2-Laser-assistierte Implantatdekontamination die Therapie periimplantärer Entzündungen optimieren kann. Weitere Studien sind erforderlich, um ein gesichertes Behandlungsprotokoll für die Periimplantitistherapie erstellen zu können.Medical Laser Application 20(1):61-70. -
Article: Advances in magnetofection—magnetically guided nucleic acid delivery
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ABSTRACT: Magnetofection is nucleic acid delivery to cells supported and site-specifically guided by the attractive forces of magnetic fields acting on nucleic acid shuttles (vectors) which are associated with magnetic nanoparticles. Recent progress with the method confirms its general applicability with small and large nucleic acids and viruses. The method's therapeutic application as well as mechanistic studies will be discussed.Journal of Magnetism and Magnetic Materials. -
Article: Titanium deposition after peri-implant care with the carbon dioxide laser.
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ABSTRACT: Titanium endosseous implants are becoming increasingly important in dentistry because of their excellent long-term results. However, it has been reported that these implants may lead to higher concentrations of titanium, especially in the lungs and kidneys. The purpose of this study, therefore, was to determine whether CO2 laser-assisted decontamination of exposed implant surfaces is associated with an increase in titanium release. In 6 beagle dogs, a total of 60 implants were placed. After osseointegration and second-stage surgery, peri-implantitis was induced by cotton floss ligatures for 12 weeks. Surgical treatment consisted of granulation tissue removal, including decontamination of the implant surface with 3 different methods. Twenty implants were decontaminated conventionally by an air-powder abrasive for 60 seconds. Another 20 implants were decontaminated by laser treatment alone. The last 20 implants were treated conventionally by air-powder abrasive and then lased. Four months later, fresh tissue samples of various tissues were evaluated by histologic and chemical analysis. Quantitative analysis indicated that titanium accumulation could be detected, especially in the spleen, liver, oral mucosa, regional lymph nodes, lung, and kidney in the beagle dog model. The concentrations found did not exceed those previously reported in the literature. These results support the hypothesis that CO2 laser-assisted therapy of ailing implants will not result in excessive titanium concentrations in tissues. Accordingly, CO2 lasers appear suitable and safe for peri-implant gingival surgery.The International journal of oral & maxillofacial implants 17(5):707-14. · 1.78 Impact Factor -
Article: Adjuvant immunotherapy of feline fibrosarcoma with recombinant feline interferon-omega.
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ABSTRACT: Recombinant feline interferon-omega (rFeIFN-omega) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility. Treatment with rFeIFN-omega in cats with fibrosarcoma is safe and feasible. Twenty domestic cats. In an open-labeled uncontrolled clinical trial 12 injections of 1 x 10(6) U/kg rFeIFN-omega were administered over a 5-week period: the 1st through 4th injections were given intratumorally, and the 5th through 12th injections were administered subcutaneously at the tumor excision site. Wide surgical excision of the tumors was carried out after the 4th injection and before the 5th injection of rFeIFN-omega. A Common Terminology Criteria for Adverse Events (CTCAE) analysis was conducted. Flow cytometry of fibrosarcoma cells after incubation with rFeIFN-omega and recombinant feline interferon-gamma was performed to assess the biological effect of rFeIFN-omega. Changes in blood cell count, increases in serum aspartate-amino-transferase activity, serum bilirubin concentration, serum creatinine and serum electrolyte concentrations, weight loss, anorexia, increased body temperature, and reduced general condition were observed but were mostly minor (grade 1 and 2) and self limiting. Eosinophilia (P = .025), neutropenia (P = .021), and weight loss (P < .001) were statistically correlated with rFeIFN-omega-treatment (analysis of parameters before treatment and after 3 injections of rFeIFN-omega). Flow cytometry of 5 unrelated feline fibrosarcoma cell lines showed increased expression of major histocompatibility complex (MHC) class I molecules (P = .026) in response to in vitro incubation with rFeIFN-omega, whereas expression of MHC class II molecules was not affected significantly. RFeIFN-omega for the treatment of feline fibrosarcoma is safe, well tolerated, and can be easily performed in practice. To assess the efficacy of the treatment, it should be tested in a placebo-controlled trial.Journal of Veterinary Internal Medicine 21(6):1340-6. · 1.99 Impact Factor