We report here our electrophysiological and psychophysiological studies of the mechanisms by which the visual system recognizes structured images with different levels of ordering. Visual stimuli consisted of textures, i.e., a set of matrixes consisting of Gabor grids. Matrixes differed in terms of the degree of ordering resulting from changes in the probability that grids with the same orientation would appear. The subject's task was to identify the dominant orientation in the stimulus. The relationship between response accuracy, reaction time, and the main characteristics of evoked potentials on the one hand, and the number of identical grids in the matrix on the other was identified. The proportion of correct responses increased and the reaction time decreased as the degree of ordering of stimuli increased. Visual evoked potentials recorded in the occipital areas showed a relationship between the amplitudes of the N2, P2, and P3 waves, with latent periods of 180, 260, and 400 msec, respectively, and matrix parameters. The amplitudes of the P3 component and the positive component recorded in the frontal leads, with a latent period of 250 msec, increased gradually as the task became simpler. The amplitude of the N2 wave also increased with increases in the number of identically oriented elements in the matrix, though this relationship was S-shaped. The magnitude of the P2 component, conversely, was maximal in response to presentation of those matrixes which were most complex to recognize and gradually decreased as the content of identically oriented grids in the matrix increased. These relationships were compared with the statistical characteristics of the stimuli and assessed in terms of the view that the visual system contains two mechanisms, i.e., local and integral image descriptions.
Despite continuous attempts to improve therapy, the outcomes of acute myeloid leukemia remain almost unchanged over last decades. Drugs made with a more complete understanding of the biology of acute myeloid leukemia do not equal the hopes for better prognosis. The best results are achieved only with high-dose chemotherapy, which is only possible for a limited number of patients. High phenotypic and genotypic heterogeneity of acute myeloid leukemia defines the relevance to develop personalized approaches to therapy, including those based on determination of individual drug sensitivity of blast cells.This article presents the results of developing an ex-vivo model of acute myeloid leukemia, as well as testing of two in vitro sensitivity assessment methods: evaluation of the genotoxicity of drugs in the micronucleus test and vitality and sensitivity to chemotherapy in sorted blast cells. Prospects of individualized therapy of acute myeloid leukemia were determined based on introduction into clinical practice and continuing the research.
Background:This abstract presents the experience of cultivating the peripheral blast cells of a patient with resistant acute myeloid leukemia (AML) and testing 2 methods for assessing the effects of chemotherapy drugs on them.Aims:Suitability examination of cell sorting (CS) and micronucleus test (MT) for assessing the genotoxicity of chemotherapy drugs.Methods:Blast cells were obtained by taking blood from a patient with multi‐resistant AML. On sampling days, the percentage of blasts in the patient's peripheral blood ranged from 50% to 75%. In total, 3 in vitro experiments were conducted.In experiment №1, 520650 CD34+ cells were sorted into 2 tubes, which were incubated for 4 days (37 °C, 5% CO2) in 5 ml of complete nutrient medium (CM): 80% RPMI‐1640, 10% fetal calf serum, 10% of the patient's original serum, 10 μl of phytohaemagglutinin and 100 U/ml penicillin.After the first day, decitabine was added to one of the samples at a concentration of 1160 ng/ml. To assess the genotoxicity of the drug at the end of cultivation, we determined the number of cells that retained viability by evaluating the results of labeling free DNA.In experiments №2 and №3, 0.5 ml of blood was cultured with 5 ml of CM. After 24 hours, various concentrations of decitabine (290 ng/ml, 580 ng/ml, 1160 ng/ml) were added to the samples of experiment №2. Daunorubicin (3400 ng/ml) was added to the samples of experiment №3, as well as its combination with interferon alpha‐2a in the calculation of 3600 IU/ml. Next, samples were cultured for 48 hours. To assess the genotoxicity in these experiments MT was used.Results:The results of experiment №1 are presented in Figure 1, №2 in table 1, №3 in table 2.Summary/Conclusion:1. CS allows selection of the required number of cells with the required phenotype and assess their viability after cultivation with high accuracy. In the sample with the addition of decitabine, living blast cells turned out to be almost 2 times less than in the control sample.imageimage2. MT can be used to assess the genotoxicity of chemotherapy drugs for peripheral blood blast cells. From the results of experiment №2, it follows that the concentration of the drug has a direct correlation with the level of its genotoxicity on blast cells. In experiment №3, the combination of daunorubicin with interferon showed much stronger genotoxic effects on blast cells compared to daunorubicin without interferon.
Direct оral Anticoagulants (DOACs) include direct thrombin inhibitor (dabigatran) and factor X inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban). The) are widely used worldwide for the prevention and treatment of venous thrombosis. The popularity of DOACs is explained by convenient and predictable pharmacodynamics, the lack of need for regular monitoring of the therapeutic effect, as well as more predictable food-drug interaction and bioavailability. However, like any other anticoagulants, DOACs are characterized by an increased risk of bleeding, especially gastrointestinal one. The correct approach to the prescription of DOACs and prevention of bleeding during treatment including the intake of anticoagulants can significantly reduce the probability of life-threatening complications. In the case of bleeding, the use of specific and nonspecific DOACs antidotes is indicated. Significant bleeding requires the attending physician to know a clear course of action in accordance with published algorithms to save the patient’s life.
Already at the very beginning of COVID-19 pandemic, it became known about the key clinical and pathogenetic significance of immunopathological reactions and disorders of hemostasis. Specific coagulopathy, microvascular thromboinflammatory organ damage, macrothrombosis and thromboembolism in the acute period of COVID-19, as well as secondary hemostasis disorders in convalescents, actualize the issues of caring patients with cardiovascular disease. COVID-19 not only increases the risk of thromboembolic events for patients with previously identified arrhythmias, but can also indirectly cause it (as a complication of infection or therapy). The aim of this work was to summarize the data and substantiate the optimal choice of prophylactic anticoagulant therapy for nonvalvular atrial fibrillation during the COVID-19 pandemic. Atrial fibrillation is not only the most common type of supraventricular tachyarrhythmia, but it is also the main underlying cause of more than half of cardioembolic stroke cases, which requires effective thromboprophylaxis. While maintaining the infectious danger for patients, the anticoagulant selection should take into account the possible dysfunctions and drug interactions during the initial infection or reinfection of COVID-19, as well as the possibility of rapid anticoagulant action reverse if surgery is required or bleeding develops. The optimal choice seems to be the use of dabigatran, which is characterized by the best safety profile for hepato- and nephrotoxicity, cytochrome P450-independent metabolism, and the presence of an antidote.
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