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1.
Am J Surg ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38553336

RESUMO

BACKGROUND: Despite improving understanding of trauma-induced coagulopathy (TIC), mortality and morbidity due to exsanguinating trauma remain high. Increased complications due to hemorrhage have been reported in blood group O, possibly due to reduced levels of von Willebrand factor (vWF). METHODS: An urban level 1 adult trauma center registry was retrospectively queried. Patients receiving ≥6 units of pRBC within 4 â€‹h of presentation were included. Patient demographics, admission labs and outcomes were obtained. Univariate and multiple logistic regression analyses were performed. RESULTS: 562 patients were identified. There were no significant differences in demographics, admission labs, or outcome between different ABO groups. After adjustment, Type A patients were more likely to be hypocoagulable compared to Type O patients (p â€‹= â€‹0.014). No mortality differences were seen between ABO types in multiple regression analysis. CONCLUSIONS: No outcome or mortality differences were seen between ABO types, therefore factors other than vWF expression should be considered to explain coagulopathy in trauma patients.

2.
ACS Omega ; 3(9): 11582-11591, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30320266

RESUMO

Diminazene, DMZ, (or berenil) has been reported as a tight binder of G-quadruplexes. G-Quadruplex structures are often located in the promotor regions of oncogenes and may play a regulatory role in gene expression based on the stability of the folding topology. In this study, attempts have been made to characterize the specificity of DMZ binding toward multiple G-quadruplex topologies or foldamers. Mutant sequences of the G-quadruplex forming promotor regions of several oncogenes were designed to exhibit restricted loop lengths and folding topologies. Circular dichroism was used to confirm the quadruplex topology of mutant BCL2, KRAS, and c-MYC sequences, human telomere (Na+ and K+) G-quadruplexes and their complexes with DMZ and analogs thereof. Isothermal titration calorimetry was used to generate a complete thermodynamic profile (ΔG, ΔH, -TΔS) for the formation of DMZ and analog complexes with the target G-quadruplexes. DMZ binds to parallel and/or mixed parallel/antiparallel quadruplex DNA motifs with stoichiometries up to 8:1 and via three binding modes with varying affinities. In the case of the parallel G-quadruplexes, with the exception of the long-looped c-MYC mutant, the highest affinity binding event (mode 1) is driven by enthalpy. DMZ binding to the long-looped c-MYC mutant exhibits a very favorable entropy change in addition to a moderately favorable enthalpy change. Mode 1 binding to the antiparallel and mixed parallel/antiparallel hTel quadruplexes is also driven by favorable enthalpy changes. In all cases, the intermediate DMZ affinity binding (mode 2) is driven almost entirely by entropy, with small or unfavorable enthalpic contributions. The weakest binding event (mode 3) is also entropically driven with small or moderate enthalpic contributions.

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