Организация выборов во всероссийское учредительное собрание на Киевщине

У статті аналізуються основні складові підготовки виборів до Всеросійських Установчих зборів у Київській губернії.The aim of this paper is to show the main stages in the Russian Constituent Assembly election process in Kiev Region. The article is based on archival documents and researches. Elections to the Russian Constituent Assembly were a very important event. The commission of the Kyiv region responsibly organized this elections, but there was a row of technical obstacles and that’s why elections were deferred. To these obstacles one can include the shortage of facilities, revolutionary events, strike of printers, transport disorders, considerable migration of population, unsatisfactory work of telegraph service, and others. Preparation of elections in Kyiv region must become a lesson for modern politician as proves that only close collaboration of all participants of elections, from ordinary electors to the greatest public servants and members of public organs can assist to organize the elections in time.В статье на основании архивных документов и напечатанных исследований анализируются главные составляющие подготовки выборов во Всероссийское Учредительное собрание в Киевской губернии

Fibrinogen-mimicking, multiarm nanovesicles for human thrombus-specific delivery of tissue plasminogen activator and targeted thrombolytic therapy

Clinical use of tissue plasminogen activator (tPA) in thrombolytic therapy is limited by its short circulation time and hemorrhagic side effects. Inspired by fibrinogen binding to activated platelets, we report a fibrinogen-mimicking, multiarm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This biomimetic system is based on the lipid nanovesicle coated with polyethylene glycol (PEG) terminally conjugated with a cyclic RGD (cRGD) peptide. Our experiments with human blood demonstrated its highly selective binding to activated platelets and efficient tPA release at a thrombus site under both static and physiological flow conditions. Its clot dissolution time in a microfluidic system was comparable to that of free tPA. Furthermore, we report a purpose-built computational model capable of simulating targeted thrombolysis of the tPA-loaded nanovesicle and with a potential in predicting the dynamics of thrombolysis in physiologically realistic scenarios. This combined experimental and computational work presents a promising platform for development of thrombolytic nanomedicines

Traitement ciblé des maladies thrombotiques grâce à des particules de polsaccharides submicroniques fonctionnalisées

Atherosclerosis is a chronic disease which may lead to acute thromboembolic events. Currentthrombolytic therapy, the intravenous injection of recombinant tissue plasminogen activator(rtPA), is administrated to lyse a vascular occlusion and restore the blood flow in the vessel.However, systemic delivery of rtPA exhibits limited clinical efficacy because of its shortplasma half-live and risks of hemorrhages. Herein, we explore the utilization of 100%polysaccharide submicronic particles as the biocompatible and biodegradable thrombustargetingnanovector for safe and efficient thrombolysis.The inflammatory adhesion molecule P-selectin was selected to be a molecular target,as it is overexpressed by the platelets and vascular endothelium upon activation. Fucoidan, asulfated polysaccharide from brown algae, was used as a targeting ligand due to its affinity toP-selectin and biocompatibility. The submicronic polysaccharide particles demonstrated theirthrombus targeting in vitro and in vivo. In the murine model of ischemic stroke, rtPAconjugated to the submicronic particles enhanced the thrombolytic activity of clinical agent invivo.To conclude, novel biocompatible fucoidan-functionalized polysaccharide particleswere designed and tested for thrombolytic therapy in preclinical models. This proof-of-conceptstudy demonstrates the promise of biomaterial-based targeted nanomedicine to improve thesafety and efficacy of systemic thrombolysis for future clinical applicationL'athérosclérose est une maladie chronique qui peut entraîner des événements thromboemboliques aigus. La thérapie thrombolytique actuelle, l'injection intraveineuse d'activateur tissulaire du plasminogène recombinant (rtPA), est utilisée pour lyser une occlusion vasculaire. Cependant, l'administration systémique de rtPA présente une efficacité clinique limitée en raison de sa courte demi-vie plasmatique et des risques d'hémorragie. Ce projet de Doctorat explore l'utilisation de particules submicroniques 100% polysaccharidiques en tant que nano vecteur ciblant le thrombus, biocompatible et biodégradable pour une thrombolyse plus sûre et plus efficace. La molécule d'adhésion inflammatoire P-sélectine a été une cible moléculaire, car elle est surexprimée par les plaquettes et l'endothélium vasculaire lors de leur activation. Le fucoïdane, un polysaccharide sulfaté issu d'algues brunes, a été utilisé comme agent de ciblage en raison de sa forte affinité pour la P-sélectine et de sa biocompatibilité. Les particules de polysaccharide ont démontré leur potentiel de ciblage du thrombus in vitro et in vivo. La conjugaison du rtPA aux particules pourrait améliorer l'activité thrombolytique de l'agent clinique in vivo dans un modèle murin d'Accident Vasculaire Cérébral ischémique. Pour conclure, de nouvelles particules submicroniques polysaccharidiques biocompatibles fonctionnalisées avec du fucoïdane ont été conçues pour effectuer une thérapie thrombolytique dans des modèles précliniques. Cette étude de preuve de concept démontre la promesse de la nanomédecine ciblée à base de biomatériaux pour améliorer la sécurité et l'efficacité de la thrombolyse systémique en clinique

Ultrasound molecular diagnosis and targeted treatment of thrombotic diseases

L'athérosclérose est une maladie chronique qui peut entraîner des événements thromboemboliques aigus. La thérapie thrombolytique actuelle, l'injection intraveineuse d'activateur tissulaire du plasminogène recombinant (rtPA), est utilisée pour lyser une occlusion vasculaire. Cependant, l'administration systémique de rtPA présente une efficacité clinique limitée en raison de sa courte demi-vie plasmatique et des risques d'hémorragie. Ce projet de Doctorat explore l'utilisation de particules submicroniques 100% polysaccharidiques en tant que nano vecteur ciblant le thrombus, biocompatible et biodégradable pour une thrombolyse plus sûre et plus efficace. La molécule d'adhésion inflammatoire P-sélectine a été une cible moléculaire, car elle est surexprimée par les plaquettes et l'endothélium vasculaire lors de leur activation. Le fucoïdane, un polysaccharide sulfaté issu d'algues brunes, a été utilisé comme agent de ciblage en raison de sa forte affinité pour la P-sélectine et de sa biocompatibilité. Les particules de polysaccharide ont démontré leur potentiel de ciblage du thrombus in vitro et in vivo. La conjugaison du rtPA aux particules pourrait améliorer l'activité thrombolytique de l'agent clinique in vivo dans un modèle murin d'Accident Vasculaire Cérébral ischémique. Pour conclure, de nouvelles particules submicroniques polysaccharidiques biocompatibles fonctionnalisées avec du fucoïdane ont été conçues pour effectuer une thérapie thrombolytique dans des modèles précliniques. Cette étude de preuve de concept démontre la promesse de la nanomédecine ciblée à base de biomatériaux pour améliorer la sécurité et l'efficacité de la thrombolyse systémique en clinique.Atherosclerosis is a chronic disease which may lead to acute thromboembolic events. Currentthrombolytic therapy, the intravenous injection of recombinant tissue plasminogen activator(rtPA), is administrated to lyse a vascular occlusion and restore the blood flow in the vessel.However, systemic delivery of rtPA exhibits limited clinical efficacy because of its shortplasma half-live and risks of hemorrhages. Herein, we explore the utilization of 100%polysaccharide submicronic particles as the biocompatible and biodegradable thrombustargetingnanovector for safe and efficient thrombolysis.The inflammatory adhesion molecule P-selectin was selected to be a molecular target,as it is overexpressed by the platelets and vascular endothelium upon activation. Fucoidan, asulfated polysaccharide from brown algae, was used as a targeting ligand due to its affinity toP-selectin and biocompatibility. The submicronic polysaccharide particles demonstrated theirthrombus targeting in vitro and in vivo. In the murine model of ischemic stroke, rtPAconjugated to the submicronic particles enhanced the thrombolytic activity of clinical agent invivo.To conclude, novel biocompatible fucoidan-functionalized polysaccharide particleswere designed and tested for thrombolytic therapy in preclinical models. This proof-of-conceptstudy demonstrates the promise of biomaterial-based targeted nanomedicine to improve thesafety and efficacy of systemic thrombolysis for future clinical applicatio

Fucoidan-functionalized polysaccharide submicroparticles loaded with alteplase for efficient targeted thrombolytic therapy

International audienceIntravenous administration of fibrinolytic drugs is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and might trigger hemorrhagic transformations. Therefore, it is mandatory to develop innovative nanomedicine-based solutions for more efficient and safer thrombolysis with biocompatible and biodegradable thrombustargeted nanocarrier. Herein, fucoidan-functionalized hydrogel polysaccharide submicroparticles with high biocompatibility are elaborated by the inverse miniemulsion / crosslinking method. They are loaded with the gold standard fibrinolytic-alteplaseto direct site-specific fibrinolysis due to nanomolar interactions between fucoidan and P-selectin overexpressed on activated platelets and endothelial cells in the thrombus area. The thrombus targeting properties of these particles are validated in a microfluidic assay containing recombinant P-selectin and activated platelets under arterial and venous blood shear rates as well as in vivo. The experiments on the murine model of acute thromboembolic ischemic stroke support this product's therapeutic efficacy, revealing a faster recanalization rate in the middle cerebral artery than with free alteplase, which reduces post-ischemic cerebral infarct lesions and blood-brain barrier permeability. Altogether, this proof-of-concept study demonstrates the potential of a biomaterial-based targeted nanomedicine for the precise treatment of acute thrombotic events, such as ischemic stroke

Functionalized Polymer Microbubbles as New Molecular Ultrasound Contrast Agent to Target P-selectin in Thrombus

International audienceThrombotic diseases rarely cause symptoms until advanced stage and sudden death. Thus, early detection of thrombus by a widely spread imaging modality can improve the prognosis and reduce mortality. Here, polymer microbubbles (MBs) made of degradable poly(IsoButylCyanoAcrylate) and functionalized with fucoidan (Fucoidan-MBs) were designed as a new targeted ultrasound contrast agent to image venous thrombus. The physicochemical characterizations demonstrate that the MBs with fucoidan surface exhibit a size of 2–6 μm and stability in suspension at 4 °C up to 2 months. MBs exhibit high echogenicity and could be completely burst under high destructive pulse. Flow chamber experiments on activated human platelets show a higher affinity of Fucoidan-MBs than control anionic MBs (CM-Dextran-MBs) under shear stress conditions. In vivo analysis by ultrasound and histological results demonstrate that Fucoidan-MBs are localized in rat venous thrombotic wall, whereas few CM-Dextran-MBs are present. In addition, the binding of Fucoidan-MBs in healthy vein is not observed. Collectively, Fucoidan-MBs appear as a promising functionalized carrier for ultrasound molecular imaging in thrombotic diseases