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Grunewald, Germany

Garcia-Estrada C.,Institute Biotecnologia Of Leon Inbiotec | Ullan R.V.,Institute Biotecnologia Of Leon Inbiotec | Albillos S.M.,Institute Biotecnologia Of Leon Inbiotec | Fernandez-Bodega M.A.,Institute Biotecnologia Of Leon Inbiotec | And 5 more authors.
Chemistry and Biology | Year: 2011

A single gene cluster of Penicillium chrysogenum contains genes involved in the biosynthesis and secretion of the mycotoxins roquefortine C and meleagrin. Five of these genes have been silenced by RNAi. Pc21g15480 (rds) encodes a nonribosomal cyclodipeptide synthetase for the biosynthesis of both roquefortine C and meleagrin. Pc21g15430 (rpt) encodes a prenyltransferase also required for the biosynthesis of both mycotoxins. Silencing of Pc21g15460 or Pc21g15470 led to a decrease in roquefortine C and meleagrin, whereas silencing of the methyltransferase gene (Pc21g15440; gmt) resulted in accumulation of glandicolin B, indicating that this enzyme catalyzes the conversion of glandicolin B to meleagrin. All these genes are transcriptionally coregulated. Our results prove that roquefortine C and meleagrin derive from a single pathway. © 2011 Elsevier Ltd All rights reserved. Source


Hahn K.,Universitatmedizin Charite | Baumeister C.,Internistische Praxis | Schielke E.,Neurologische Praxis
Zeitschrift fur Neuropsychologie | Year: 2011

Acute encephalitis is a rare disease mainly occurring sporadically. Only limited data as to the long-term prognosis in particular for the regeneration of cognition is available. This study investigated prospectively what influence encephalitis has on cognitive parameters. People who matched the patients in age, gender and level of education were used as a control group. The period between the acute illness and the follow-up investigation amounted to 6 to 93 months. The study showed a favourable outcome in most of the patients. Impaired executive and motivation functions were the most common findings independent of the cause of encephalitis. Post-encephalitis epilepsy revealed to have a negative effect on cognitive rehabilitation. © 2011 Verlag Hans Huber, Hogrefe AG, Bern. Source


Czabanka M.,Universitatmedizin Charite | Bruenner J.,Universitatmedizin Charite | Parmaksiz G.,Universitatmedizin Charite | Broggini T.,Universitatmedizin Charite | And 13 more authors.
European Journal of Cancer | Year: 2013

Introduction: Combined antiangiogenic and cytotoxic treatment represents an appealing treatment approach for malignant glioma. In this study we characterised the antitumoural and microvascular consequences of sunitinib (Su) and temozolomide (TMZ) therapy and verified the ideal treatment protocol, with special focus on a potential therapeutic window for combined scheduling. Materials and Methods: O6-Methylguanine methyltransferase (MGMT) status was analysed by pyrosequencing. Tumour growth of subcutaneous xenografts was assessed under different treatment protocols (TMZ, SU, SU followed by TMZ, TMZ followed by SU, combined TMZ/SU). Intravital microscopy (dorsal skinfold chamber model) assessed microvascular consequences. Immunohistochemistry included tumour and endothelial cell proliferation, apoptosis and vascular pericyte coverage. Real-time polymerase chain reaction (RT-PCR) analysed the expression of angiogenesis-related pathways in response to therapy. Results: Combined TMZ/SU resulted in significantly reduced tumour growth compared to either monotreatment (TMZ: 106 ± 13mm3; SU: 114 ± 53mm3; TMZ/SU: 34 ± 7mm3) by additional antiangiogenic effects and synergistic induction of apoptosis versus TMZ monotreatment. Sequential treatment protocols did not show additive antitumour responses. TMZ/SU aggravated vascular resistance mechanisms characterised by significantly higher blood flow rate (TMZ: 74 ± 34 μl/s; SU: 164 ± 36 μl/s; TMZ/SU: 254 ± 95 μl/s), reduced permeability (TMZ: 1.05 ± 0.02; SU: 0.99 ± 0.07; TMZ/SU: 0.89 ± 0.05) and recovery of pericyte-endothelial interactions (TMZ: 89 ± 7%; SU: 67 ± 9%, TMZ/SU:80 ± 10%) versus either monotreatment. Vascular resistance was paralleled by an increase in Ang-1 and Tie-2 and by the downregulation of Dll4. Conclusion: Sequential application of TMZ and SU in the angiogenic window does not add antitumour efficacy to monotherapy. Simultaneous application yields beneficial tumour control due to additive antiangiogenic and proapoptotic effects. Combined treatment may aggravate pericyte-mediated vascular resistance mechanisms by altering Ang-1-Tie-2 and Dll4/Notch pathways.© 2013 Elsevier Ltd. All rights reserved. Source

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