Document Detail


Compatibility of recombinant tissue plasminogen activator and bevacizumab co-applied for neovascular age-related macular degeneration with submacular hemorrhage.
MedLine Citation:
PMID:  22410628     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To investigate the compatibility of recombinant tissue plasminogen activator (rtPA) and bevacizumab in vitro because during surgery, rtPA or rtPA-induced plasmin may cleave and inactivate bevacizumab.
METHODS: To simulate the intraoperative range of mixing ratios of rtPA, bevacizumab, and subretinal blood, we calculated the volumes of 12 submacular hemorrhages (SHs) with a spherical cap formula using measurements derived from fundus photographs and spectral-domain optical coherence tomographic images. Bevacizumab was incubated with rtPA or plasmin before gel electrophoresis with Coomassie blue and silver staining. The anti-angiogenetic activity of bevacizumab in the presence of rtPA with or without clotted human blood or of plasmin was quantified by vascular endothelial growth factor–enzyme-linked immunosorbent assay after incubation with the supernatant of porcine retinal pigment epithelium cell cultures.
RESULTS: The mean (SD) volume of SH was 28.6 (24.7) mm3 (range, 6.2-94.6 mm3). In sodium dodecyl sulfate–polyacrylamid electrophoresis with Coomassie blue or silver staining, bevacizumab displayed characteristic patterns of protein bands. No additional fragments were detected in co-application of bevacizumab with either rtPA or plasmin. The anti-angiogenetic activity of bevacizumab remained unchanged in co-application with rtPA with or without blood or plasmin.
CONCLUSIONS: We demonstrated the absence of cleavage or functional inactivation of bevacizumab by rtPA in an in-vitro model of their intraoperative co-application as a treatment of SH.
CLINICAL RELEVANCE: In clinical practice, rtPA and bevacizumab can be co-applied as a treatment for neovascular age-related macular degeneration with SH to simultaneously clear SH and reduce choroidal new vessel activity.
Authors:
Alexa Klettner; Svenja Puls; Felix Treumer; Johann Roider; Jost Hillenkamp
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Archives of ophthalmology     Volume:  130     ISSN:  1538-3601     ISO Abbreviation:  Arch. Ophthalmol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-09-07     Completed Date:  2012-10-12     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  7706534     Medline TA:  Arch Ophthalmol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  875-881     Citation Subset:  AIM; IM    
Affiliation:
Department of Ophthalmology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / pharmacology*
Animals
Antibodies, Monoclonal, Humanized / pharmacology*
Cells, Cultured
Drug Interactions
Drug Therapy, Combination
Electrophoresis, Polyacrylamide Gel
Enzyme-Linked Immunosorbent Assay
Fibrinolysin / pharmacology
Fibrinolytic Agents / pharmacology*
Humans
Recombinant Proteins / pharmacology
Retinal Hemorrhage / drug therapy*,  metabolism
Retinal Pigment Epithelium / drug effects,  metabolism
Swine
Tissue Plasminogen Activator / pharmacology*
Tomography, Optical Coherence
Vascular Endothelial Growth Factor A / antagonists & inhibitors
Wet Macular Degeneration / drug therapy*,  metabolism
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal, Humanized; 0/Fibrinolytic Agents; 0/Recombinant Proteins; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 2S9ZZM9Q9V/bevacizumab; EC 3.4.21.68/Tissue Plasminogen Activator; EC 3.4.21.7/Fibrinolysin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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