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- Gyongyosi, M, et al.
(författare)
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Platelet activation and high tissue factor level predict acute stent thrombosis in pig coronary arteries: prothrombogenic response of drug-eluting or bare stent implantation within the first 24 hours
- 2006
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Ingår i: Thrombosis and haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 96:2, s. 202-209
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Tidskriftsartikel (refereegranskat)abstract
- Increased thrombogenicity of drug-eluting stents (DESs) has recently been reported.The aim of the present study was to investigate the prothrombogenic effect of DESs and Bare stents, and determine factors predictive of acute stent thrombosis (AST) in preclinical experiments using new stent design or coating.Circulating preand post-stenting parameters of platelet activation (mean platelet volume, MPV; platelet distribution width, platelet large cell ratio), thrombin activation (thrombin-antithrombin complex, TAT and prothrombin fragments, F1+2), tissue factor antigen (TF-ag) and -activity (TF-act) and plasminogen activator inhibitor-1 (PAI-1) were measured in 141 consecutive pigs. Stent implantations were performed after pretreatment with aspirin and clopidogrel with unfractionated heparin anticoagulation. Nineteen pigs (groups AST-DES, n=12; and AST-Bare, n=7) died mean 6.3 ± 2.9 h after stent implantation from AST.The remaining 122 control (C) pigs (groups C-DES,n=76,and C-Bare,n=46) survived the 1-month follow-up. Non-significantly elevated levels of post-stent F1+2 and TAT were measured in AST groups. Post-stenting MPV was increased significantly in the groups ASTDES and AST-Bare as compared with the groups C-DES and C-Bare (11.73 ± 1.12 and 11.6 ± 0.68 vs. 8.85 ± 0.78 and 9.04 ± 0.81 fL; p<0.001), similarly toTF-ag (189.1± 87.5 and 127 ± 34.9 vs. 42.5 ± 24.6 and 35.3 ± 37.6 pg/ml; p<0.001, respectively),TF-act (3.23 ± 0.95 and 2.73 ± 1.68 vs. 1.43 ± 1.12 and 1.61 ± 1.31 pM; p<0.01, respectively) and PAI-1 (99.1 ± 15.8 and 99 ± 14.7 vs.53.4 ± 40.2 and 46.9 ± 42.4 ng/ml;p<0.01,respectively).Multivariate analysis revealed elevated post-stenting plasma levels of TF-ag (p=0.016) and MPV (p=0.001) as independent risk factors for developing AST within the first 24 h in a porcine coronary stent model.
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- Hevesi, Z, et al.
(författare)
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Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2
- 2022
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Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- First-generation vaccines against SARS-CoV-2 do not provide adequate immune protection. Therefore, we engineered a divalent gene construct combining the receptor-binding domain (RBD) of the spike protein and the immunodominant region of the viral nucleocapsid. This fusion protein was produced in either E. coli or a recombinant baculovirus system. Subsequently, the fusion protein was mixed with adjuvant and administered to mice in a prime-booster mode. Mice (72%) produced an IgG response against both proteins (titer: 10−4–10−5) 14 days after the first booster injection, which was increased to 100% by a second booster. Comparable IgG responses were detected against the delta, gamma and omicron variants of the RBD region. Durability testing revealed IgGs beyond 90 days. In addition, cytolytic effector cell molecules were increased in lymphocytes isolated from peripheral blood. Ex vivo stimulation of T cells by nucleocapsid and RBD peptides showed antigen-specific upregulation of CD44 among the CD4+ and CD8+ T cells of vaccinated mice. No side effect was documented in the central nervous system. Cumulatively, these data represent a proof-of-principle approach alternative to existing mRNA vaccination strategies.
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