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187 results on '"Lehle K"'

15. Protective function of pirfenidone and everolimus on the development of chronic allograft rejection after experimental lung transplantation

Author

Suesskind-Schwendi, M. von, Heige, E. l, Pfaehler, S., Haneya, A., Schmid, C., Hirt, S.W., and Lehle, K.

Subjects
Chronic rejection, Lung transplantation, 6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología [CDU], Rat, Everolimus, Pirfenidone
Abstract

Long-term survival of lung allografts is limited by chronic rejection (CR). Oxidative stress (OxS) plays a central role in the development of CR. We investigated the influence of pirfenidone (alone or in combination with everolimus) on OxS and CR. A rat model of left lung allo-transplantation (F344- to-WKY) was used to evaluate the effects of pirfenidone alone [0,85% in chow from postoperative day (POD) -3 to 20/60] and in combination with everolimus [2,5 mg/kg bw daily from POD 7 to 20/60]. Allografts of non-treated animals, everolimus treated animals and right, non-transplanted lungs were used as references. Immunohistology of myeloperoxidase (MPO), haemoxygenase-1 (HO-1), iron and platelet-derivedgrowth-factor-receptor-alpha (PDGFR-a) were performed. On POD 20, all groups showed severe acute rejection (ISHLT A3-4/B1R-B2R). Groups treated with pirfenidone showed a lower interstitial inflammatory infiltration and a lower participation of highly fibrotic degenerated vessels (ISHLT-D2R). In the long term follow up (POD 60), pirfenidone alone significantly reduced chronic airway rejection (ISHLT-C; p≤0.05), interstitial fibrosis (IF; p≤0.05), content of collagen (p≤0.05), expression of PDGFR-a (p≤0.05) and the deposition of iron (p≤0.05). All groups treated with pirfenidone showed a high expression of the cytoprotective enzyme HO-1 (p≤0.05). The additional application of everolimus resulted in a significant decrease of chronic airway rejection (ISHLT-C; p≤0.05), vasculopathy (ISHLT; p≤0.05) and IF (p≤0.05). In conclusion, early application of pirfenidone inhibited the progression of CR by its anti-fibrotic and anti-oxidative properties. The additional application of an m-TOR-inhibitor increased the anti-fibrotic effects of pirfenidone which resulted in a reduction of CR after experimental LTx.

Published
2016

20. Assessment of cisplatin concentration and penetration depth in human lung tissue after hyperthermic exposure

Author

Ried, M., Lehle, K., Bielenberg, K., Potzger, T., Braune, N., Neu, R., Bednarski, P., and Hofmann, H. S.

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Only limited data are available about the characteristics and impact of cisplatin regarding the lung tissue after radical pleurectomy followed by hyperthermic intrathoracic chemotherapy perfusion. Therefore, purpose of this study was to evaluate the concentration and penetration depth of [for full text, please go to the a.m. URL], Gemeinsame Jahrestagung der Deutschen, Österreichischen und Schweizerischen Gesellschaft für Thoraxchirurgie

Published
2013

21. Synergism of imatinib mesylate and everolimus in attenuation of bronchiolitis obliterans after rat LTX

Author

Suesskind-Schwendi, M. von, Valenti, Verena, Haneya, Assad, Pühler, T., Bewig, B., Schmid, C., Hirt, S.W., and Lehle, K.

Subjects
Lung transplantation, 5 - Ciencias puras y naturales::57 - Biología::576 - Biología celular y subcelular. Citología [CDU], Rat
Abstract

Bronchiolitis obliterans (BO) is a progressive and fatal disease after lung transplantation (LTX). Dysregulated growth factor-induced proliferation of myofibroblasts seems to be responsible for the development of BO. The aim was to confirm the efficacy of both inhibitors of receptor tyrosine kinases (RTKI) and of mammalian target of rapamycin (mTORI) after rat LTX. We used a rat model of left lung allotransplantation (F344-to-WKY) to evaluate the effect of imatinib (RTKI; 20 mg/kg/day; postoperative day (POD) 0-100) alone or in combination with everolimus (mTORI; 2.5 mg/kg/day; POD 14-100). Non-treated animals were the reference. In non-treated rats, acute rejection (AR) peaked between POD 20 and 30 (19/19) and ended in chronic rejection (CR) on POD 60/100 (12/12). Imatinib alone did not prevent AR (6/6), but attenuated the degree of degenerated bronchioles on POD 30 (non-treated, 57%; imatinib, 4%), and increased the allografts free of CR on POD 60/100 (3/12). A combination of imatinib and everolimus significantly reduced AR, attenuated fibrotic degenerated bronchioles (5%) and vessels (non-treated, 24%; combination therapy, 11%) on POD 30, and reduced fibrotic degenerated vessels (non-treated, 97%; combination therapy, 43%) and bronchioles (non-treated, 88%; combination therapy, 34%) on POD 60/100. Fifty percent of the animals were completely free of BO and vasculopathy. In conclusion, co-application of RTKI and mTORI attenuated the development of BO and vasculopathy. Thus, imatinib might be an interesting therapeutic approach after LTX.

Published
2013

49. Das STEMMAT-Projekt als Teil der Gesundheitsinitiative BayernAktiv: Adulte Stammzellen aus Nabelschnur und -blut als Alternative zur embryonalen Stammzellforschung

Author

Jacobs, V., primary, Niemeyer, M., additional, Gottschalk, N., additional, Schneider, K., additional, Kiechle, M., additional, Oostendorp, R., additional, Peschel, C., additional, Hönicka, M., additional, Lehle, K., additional, Birnbaum, D., additional, Meyer, T., additional, Rapp, S., additional, Burkhart, J., additional, Aigner, J., additional, Eblenkamp, M., additional, and Wintermantel, E., additional

Published
2006
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