Time-dependent ultrastructural changes during venous thrombogenesis and thrombus resolution.

Background: Deep vein thrombosis is a common vascular event that can result in debilitating morbidity and even death due to pulmonary embolism. Clinically, patients with faster resolution of a venous thrombus have improved prognosis, but the detailed structural information regarding changes that occur in a resolving thrombus over time is lacking.

Objectives: To define the spatial-morphologic characteristics of venous thrombus formation, propagation, and resolution at the submicron level over time.

Aortic dissection detection and thrombus structure quantification using volumetric ultrasound, histology, and scanning electron microscopy.

Aortic dissection occurs when a weakened portion of the intima tears, and a separation of layers propagates along the aortic wall to form a false lumen filled with active blood flow or intramural thrombus. The unpredictable nature of aortic dissection formation and need for immediate intervention leaves limited serial human image data to study the formation and morphological changes that follow dissection. We used volumetric ultrasound examination, histology, and scanning electron microscopy (SEM) to examine intramural thrombi at well-defined timepoints after dissection occurs in apolipoprotein E-deficient mice infused with angiotensin II (n = 71).

Fibrous gels modelled as fluid-filled continua with double-well energy landscape.

Several biological materials are fibre networks infused with fluid, often referred to as fibrous gels. An important feature of these gels is that the fibres buckle under compression, causing a densification of the network that is accompanied by a reduction in volume and release of fluid. Displacement-controlled compression of fibrous gels has shown that the network can exist in a rarefied and a densified state over a range of stresses.

Structure, mechanical properties, and modeling of cyclically compressed pulmonary emboli.

Pulmonary embolism occurs when blood flow to a part of the lungs is blocked by a venous thrombus that has traveled from the lower limbs. Little is known about the mechanical behavior of emboli under compressive forces from the surrounding musculature and blood pressure. We measured the stress-strain responses of human pulmonary emboli under cyclic compression, and showed that emboli exhibit a hysteretic stress-strain curve.

The distinctive structure and composition of arterial and venous thrombi and pulmonary emboli.

Although arterial and venous thromboembolic disorders are among the most frequent causes of mortality and morbidity, there has been little description of how the composition of thrombi and emboli depends on their vascular origin and age. We quantified the structure and composition of arterial and venous thrombi and pulmonary emboli using high-resolution scanning electron microscopy. Arterial thrombi contained a surprisingly large amount of fibrin, in addition to platelets.

Clot stability as a determinant of effective factor VIII replacement in hemophilia A.

Background: Factor VIII (FVIII) replacement is standard of care for patients with hemophilia A (HemA); however, patient response does not always correlate with FVIII levels. We hypothesize this may be in part due to the physical properties of clots and contributions of fibrin, platelets, and erythrocytes, which may be important for hemostasis.

Objective: To understand how FVIII contributes to effective hemostasis in terms of clot structure and mechanical properties.

[Inventive activity of the Department of Metabolism Regulation of the Palladin Institute of Biochemistry of NAS of Ukraine].

The article is devoted to the inventive activity of the Department of Metabolism Regulation of the Palladin Institute of Biochemistry of NAS of Ukraine in the context of the history of its inception, development and the research activities of its founder, academician of NAS of Ukraine M. F. Guly as well as his students and followers.

Molecular and Physical Mechanisms of Fibrinolysis and Thrombolysis from Mathematical Modeling and Experiments.

Despite the common use of thrombolytic drugs, especially in stroke treatment, there are many conflicting studies on factors affecting fibrinolysis. Because of the complexity of the fibrinolytic system, mathematical models closely tied with experiments can be used to understand relationships within the system. When tPA is introduced at the clot or thrombus edge, lysis proceeds as a front.

Phase transitions during compression and decompression of clots from platelet-poor plasma, platelet-rich plasma and whole blood.

Unlabelled: Blood clots are required to stem bleeding and are subject to a variety of stresses, but they can also block blood vessels and cause heart attacks and ischemic strokes. We measured the compressive response of human platelet-poor plasma (PPP) clots, platelet-rich plasma (PRP) clots and whole blood clots and correlated these measurements with confocal and scanning electron microscopy to track changes in clot structure. Stress-strain curves revealed four characteristic regions, for compression-decompression: (1) linear elastic region; (2) upper plateau or softening region; (3) non-linear elastic region or re-stretching of the network; (4) lower plateau in which dissociation of some newly made connections occurs.

[The algorithm for the determination of the sufficient number of dynamic electroneurostimulation procedures based on the magnitude of individual testing voltage at the reference point].

Unlabelled: This article was designed to present evidence of the advantages of the personified approach to the treatment of the patients presenting with arterial hypertension (AH), lumbar spinal dorsopathy (LSD), chronic obstructive pulmonary disease (COPD), and duodenal ulcer (DU) at the stage of exacerbation obtained by the measurements of testing voltage at the reference point (Utest).

Aim: The objective of the present study was to develop the algorithm for the determination of the sufficient number (optimal duration) of therapeutic procedures of the protracted treatment with the use of the Utest at the reference point.

The Patients And Methods: The study included 647 patients (439 women and 208 men at the age varying from 25 to 72 years) with grade I-II AH, DU at the stage of exacerbation, grades II and III lumbar spinal dorsopathy, grade II-III COPD.

Polyphosphate delays fibrin polymerisation and alters the mechanical properties of the fibrin network.

Polyphosphate (polyP) binds to fibrin(ogen) and alters fibrin structure, generating a heterogeneous network composed of 'knots' interspersed by large pores. Here we show platelet-derived polyP elicits similar structural changes in fibrin and examine the mechanism by which polyP alters fibrin structure. Polymerisation of fibrinogen with thrombin and CaCl was studied using spinning disk confocal (SDC) microscopy.

[Inventive activity of the Departments of Chemistry and Biochemistry of Enzymes, and Protein Structure and Function of the Palladin Institute of Biochemistry of NAS of Ukraine. Part III. Diagnostic test-systems for analysis of fibrinolysis blood system and novel approaches to thrombosis treatment].

This article continues analysis of scientific achievements of the Institute of Biochemistry in the study of hemostasis system. Two previous articles were focused on the studies of blood coagulation proteins and development of the immune-enzyme test-systems for evaluation of the risk of thrombosis upon various pathologies. This article highlights the research on the blood fibrinolysis system and new approaches to thrombosis treatment, which were developed (and are under development) in the Palladin Institute of Biochemistry of the NAS of Ukraine, in particular, in the Department of Chemistry and Biochemistry of Enzymes headed previously by Dr.

[The effectiveness of the application of dynamic electrical neurostimulation for the treatment of dorsalgias of the lumbar-sacral localization].

Dynamic electrical neurostimulation (DENS) is a variant of transcutaneous electrical neurostimulation based on the use of biological feedback monitoring the surface impedance of the skin. The present study was designed to estimate the effectiveness of the application of dynamic electrical neurostimulation for the treatment of dorsalgias of the lumbar-sacral localization in comparison with the standard combined treatment including pharmacotherapy, massage, and therapeutic physical culture exercises. The data obtained indicate that the inclusion of DENS in the standard treatment protocol promotes the regression of pain and neurological symptoms; moreover, it accelerates the achievement of clinical remission.

Effects of unidirectional flow shear stresses on the formation, fractal microstructure and rigidity of incipient whole blood clots and fibrin gels.

Incipient clot formation in whole blood and fibrin gels was studied by the rheometric techniques of controlled stress parallel superposition (CSPS) and small amplitude oscillatory shear (SAOS). The effects of unidirectional shear stress on incipient clot microstructure, formation kinetics and elasticity are reported in terms of the fractal dimension (df) of the fibrin network, the gel network formation time (TGP) and the shear elastic modulus, respectively. The results of this first haemorheological application of CSPS reveal the marked sensitivity of incipient clot microstructure to physiologically relevant levels of shear stress, these being an order of magnitude lower than have previously been studied by SAOS.

Molecular mechanisms of the effect of ultrasound on the fibrinolysis of clots.

Background: Ultrasound accelerates tissue-type plasminogen activator (t-PA)-induced fibrinolysis of clots in vitro and in vivo.

Objective: To identify mechanisms for the enhancement of t-PA-induced fibrinolysis of clots.

Methods: Turbidity is an accurate and convenient method, not previously used, to follow the effects of ultrasound.

[The experience with the application of dynamic electroneurostimulation in clinical medicine. A multicenter study].

The ever growing occurrence of iatrogenic pathologies under present conditions is responsible for the high percentage of adverse reactions associated with medicamental therapy. It emphasizes the necessity of the more extensive application of non-pharmacological products and physiotherapeutic methods free of this disadvantage. Dynamic electroneurostimulation (DENS) is one of the up-to-date promising therapeutic and prophylactic modality for this purpose by virtue of its broad spectrum of action.

Enhanced lysis and accelerated establishment of viscoelastic properties of fibrin clots are associated with pulmonary embolism.

The factors that contribute to pulmonary embolism (PE), a potentially fatal complication of deep vein thrombosis (DVT), remain poorly understood. Whereas fibrin clot structure and functional properties have been implicated in the pathology of venous thromboembolism and the risk for cardiovascular complications, their significance in PE remains uncertain. Therefore, we systematically compared and quantified clot formation and lysis time, plasminogen levels, viscoelastic properties, activated factor XIII cross-linking, and fibrin clot structure in isolated DVT and PE subjects.

Fibrin clots are equilibrium polymers that can be remodeled without proteolytic digestion.

Fibrin polymerization is a necessary part of hemostasis but clots can obstruct blood vessels and cause heart attacks and strokes. The polymerization reactions are specific and controlled, involving strong knob-into-hole interactions to convert soluble fibrinogen into insoluble fibrin. It has long been assumed that clots and thrombi are stable structures until proteolytic digestion.

[Changes of hemodynamics during the treatment of patients with neurologic pain syndromes by the method of dynamic electrical neurostimulation].

The Doppler ultrasound technique was used to study blood flow characteristics for the evaluation of the efficacy of the treatment of painful neurological syndromes with the help of a DiaDENS apparatus allowing for dynamic changes of electrostimulation parameters. A significant improvement of the extracranial cerebral blood flow was achieved as early as the mid-course of 10 treatment sessions when the most pronounced stabilization of the clinical characteristics was apparent. Marked heterogeneity of responses of extracranial vessels to the therapeutic effect of dynamic electrostimulation (DENS) was documented, possibly due to the redistribution of the blood flow in certain vascular areas during the treatment.

Visualization and identification of the structures formed during early stages of fibrin polymerization.

We determined the sequence of events and identified and quantitatively characterized the mobility of moving structures present during the early stages of fibrin-clot formation from the beginning of polymerization to the gel point. Three complementary techniques were used in parallel: spinning-disk confocal microscopy, transmission electron microscopy, and turbidity measurements. At the beginning of polymerization the major structures were monomers, whereas at the middle of the lag period there were monomers, oligomers, protofibrils (defined as structures that consisted of more than 8 monomers), and fibers.

Fibrinogen beta-chain tyrosine nitration is a prothrombotic risk factor.

Elevated levels of circulating fibrinogen are associated with an increased risk of atherothrombotic diseases although a causative correlation between high levels of fibrinogen and cardiovascular complications has not been established. We hypothesized that a potential mechanism for an increased prothrombotic state is the post-translational modification of fibrinogen by tyrosine nitration. Mass spectrometry identified tyrosine residues 292 and 422 at the carboxyl terminus of the beta-chain as the principal sites of fibrinogen nitration in vivo.

Dynamic imaging of fibrin network formation correlated with other measures of polymerization.

Using deconvolution microscopy, we visualized in real time fibrin network formation in the hydrated state. Individual mobile fibers were observed before the gel point determined by eye. After gelation, an initial fibrin network was seen, which evolved over time by addition of new fibers and elongation and branching of others.

Incorporation of fibrin molecules containing fibrinopeptide A alters clot ultrastructure and decreases permeability.

Previous studies have shown that a heterozygous mutation in the fibrinogen Aalpha chain gene, which results in an Aalpha R16C substitution, causes fibrinolytic resistance in the fibrin clot. This mutation prevents thrombin cleavage of fibrinopeptide A from mutant Aalpha R16C chains, but not from wild-type Aalpha chains. However, the mechanism underlying the fibrinolytic resistance is unclear.