Method for evaluating thrombin concentration based on the data of monitoring the viscoelastic properties of native blood in the process of hemocoagulation

The process of native blood coagulation was studied with the resonant-acoustic method using the technology of low-frequency piezothromboelastography. It is shown that the experimental curve of time dependence of the piezoelectric sensor signal amplitude reflects the change in the rheological properties of blood during coagulation. A formula is obtained that relates the change in the concentration of thrombin to the rate of change in the complex coefficient of blood viscosity. A method has been developed for assessing thrombin concentration during fibrinogenesis based on the technology of piezothromboelastography using a resonant-acoustic method for determining the viscoelastic properties of whole blood. The results of calculating the thrombin concentration by this method are compared with the results of the thrombin generation test

Influence of adhesion on measurement of viscoelastic characteristics of whole blood using resonant-acoustic method

The effect of blood adhesion on the amplitude-frequency characteristics of a piezoelectric sensor in the method of low-frequency piezothromboelastography is studied. As a result of adhesion, a layer of blood cells can accumulate on the surface of the resonator needle immersed in blood, which changes its configuration and mass and, as a consequence, its amplitude-frequency characteristics. Experiments showed that during coagulation, the free frequency of the resonator needle oscillations decreases in direct proportion to the increase in the mass of adhered blood. To confirm this regularity, we carried out a numerical experiment on the basis of 3D-mathematical model of a piezoelectric sensor used in the piezotromboelastograph ARP-01M Mednord. The experiment was performed with the help of the COMSOL Multiphysics® 4.2 software package and the finite element method. We calculated the change in the free frequency of the resonator needle oscillations as a function of the adhered blood mass and their time dependence in the blood coagulation process. It is shown that during coagulation, the mass of adhered blood increases starting from the third minute and reaches its maximum of 0.42 milligram in 15 minutes, which leads to a noticeable shift in the resonance frequency of the piezoelectric sensor towards lower frequencies

The influence of dynamic blood viscosity on coronary blood flow in stenotic artery

The paper proposes the calculation technique for the coronary blood flow in stenotic arteries with respect to the blood viscosity affecting the parameters of the fractional flow reserve based on the data analysis of the multispectral computed tomography. The calculation technique is also based on regulations that determine the hemodynamics in stenotic vessels. The mathematical simulation is presented for the blood flow in a stenotic coronary artery. This simulation is based on the Navier-Stokes equations. The calculations are carried out using Comsol Multiphysics 4.2. software. The obtained results show that the distribution of the blood flow rate in the stenotic artery is not uniform, and the pressure out of the stenotic segment of the artery depends on the blood viscosity. This must be taken into consideration both in mathematical simulation and invasive coronary angiography of the fractional flow reserve. The research results can be used in effective diagnostics of coronary artery disease

Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios.

Proprotein convertases (PCs) is a protein family which includes nine highly specific subtilisin-like serine endopeptidases in mammals. The system of PCs is involved in carcinogenesis and levels of PC mRNAs alter in cancer, which suggests expression status of PCs as a possible marker for cancer typing and prognosis. The goal of this work was to assess the information value of expression profiling of PC genes. Quantitative polymerase chain reaction was used for the first time to analyze mRNA levels of all PC genes as well as matrix metalloproteinase genes MMP2 and MMP14, which are substrates of PCs, in 30 matched pairs of samples of human lung cancer tumor and adjacent tissues without pathology. Significant changes in the expression of PCs have been revealed in tumor tissues: increased FURIN mRNA level (p<0.00005) and decreased mRNA levels of PCSK2 (p<0.007), PCSK5 (p<0.0002), PCSK7 (p<0.002), PCSK9 (p<0.00008), and MBTPS1 (p<0.00004) as well as a tendency to increase in the level of PCSK1 mRNA. Four distinct groups of samples have been identified by cluster analysis of the expression patterns of PC genes in tumor vs. normal tissue. Three of these groups covering 80% of samples feature a strong elevation in the expression of a single gene in cancer: FURIN, PCSK1, or PCSK6. Thus, the changes in the expression of PC genes have a limited number of scenarios, which may reflect different pathways of tumor development and cryptic features of tumors. This finding allows to consider the mRNAs of PC genes as potentially important tumor markers

Description of the specimens studied and heat map presentation of the ratio values of gene expression in tumor vs. adjacent tissues without histological pathology.

<p>SCC, squamous cell lung carcinoma; AdC, adenocarcinoma; AdC/SCC, both AdC and SCC cells were found in the tumor tissue; SCLC, small cell lung carcinoma; P, peripheral tumor location; C, central tumor location; Y, tumor with keratinization; N, tumor without keratinization; ‘-’, no data. The heat map is shown in log₂ scale. Gray cells indicate specimens with undetectable mRNA in both tumor and normal tissues.</p

Clustering of PC genes' expression data.

<p>Specimens numbering corresponds to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055752#pone-0055752-g001" target="_blank">Fig. 1</a>. The Ratio^T/N values in the heat map were row-normalized and shown in linear scale. Gray cells indicate specimens with undetectable mRNA in both normal and cancer tissues. Branch length reflects the distance between the dendrogram nodes. The clusters found are marked as C1, C2, C3 and C4.</p

Gene designations and TaqMan Gene Expression Assays used in real-time PCR.

*<p>HGNC – HUGO Gene Nomenclature Committee (<a href="http://www.genenames.org" target="_blank">www.genenames.org</a>).</p

Correlations between expression profiles of the genes studied.

*<p>R_s is Spearman correlation coefficient (p<0.05).</p