Quantification of epicardial adipose tissue by computed tomographic scanning as a prognostic criterion of atrial fibrillation recurrence after catheter ablation.

Aim    This study focused on a systematic review and meta-analysis on the predictive role of quantifying the epicardial adipose tissue (EAT) volume using data of computed tomography (CT) in patients after catheter ablation for atrial fibrillation (AF).Material and methods    We performed a search in PubMed and Google Scholar for studies that examined the predictive value of EAT volume measured by CT for AF recurrence in patients after undergoing pulmonary venous isolation. Risk ratio (RR) values from studies, where similar scoring criteria were available, were pooled for the meta-analysis.Results    Eighteen studies were selected from 901 publications for these systematic review and meta-analysis. In total, 4087 patients were included in this analysis (mean age, 59.0 years; mean follow-up duration, 14.9 mos). Patients with recurrent AF after ablation had higher left atrial EAT volume compared to patients without relapse (weighted mean difference, 5.99 ml; 95% CI: -10.04 to -1.94; p = 0.004). An increase in left atrial EAT volume per ml was significantly associated with the development of AF recurrence after ablation (RR 1.08; 95% CI: 1.01 to 1.16; p=0.03). Patients with recurrent AF after ablation also had higher total EAT values than patients without relapse (difference in weighted values, 11.67 ml; 95% CI: -19.81 to -3.54; p = 0.005). However, no significant association was found between the total EAT volume and the risk of AF relapse (RR 1.00; 95% CI: 1.00 to 1.01; p=0.06).Conclusions    The volume of left atrial EAT measured by CT has a significant predictive value in AF patients after catheter ablation and can be used for stratification of the risk for recurrent AF.

The extent of late gadolinium enhancement predicts mortality, sudden death and major adverse cardiovascular events in patients with nonischaemic cardiomyopathy: a systematic review and meta-analysis.

AIM: To conduct a systematic review and meta-analysis with the objective of evaluating the prognostic value of extent of myocardial fibrosis by late gadolinium-enhanced cardiac magnetic resonance imaging (CMR) in non-ischaemic dilated cardiomyopathy (NICM). MATERIAL AND METHODS: The databases PubMed, EMBASE, and Google Scholar were searched for studies that investigated the prognostic value of quantification of late gadolinium enhancement (LGE) in patients with NICM. Unadjusted and adjusted hazard ratios (HRs) of uniformly defined predictors were pooled for meta-analysis. RESULTS: Fourteen studies were retrieved from 884 publications for this systematic review and meta-analysis. In total, 4,336 patients (mean age 51.2 years; mean follow-up 35.1 months) were included in the analysis. Meta-analysis showed the extent of LGE was associated with an increased risk of all-cause mortality (HR: 1.07/1% LGE; 95% confidence interval [CI]: 1.03-1.11; p=0.0003), composite arrhythmic endpoint (HR: 1.09/1% LGE; 95% CI: 1.03-1.15; p=0.002) and major adverse cardiovascular events (MACE; HR: 1.06/1% LGE; 95% CI: 1.02-1.11; p=0.005). After adjusting for baseline characteristics, the higher extent of LGE remained associated with the risk of all-cause mortality (HRadjusted: 1.07/1% LGE; 95% CI: 1.00-1.14; p=0.04), also strongly associated with the risk of composite arrhythmic endpoint (HRadjusted: 1.07; 95% CI: 1.02-1.012; p=0.004) and MACE (HRadjusted: 1.04; 95% CI: 1.01-1.08; p=0.005). CONCLUSIONS: Extent of LGE in CMR predicts all-cause mortality, arrhythmic events, and MACE. Collectively, these findings emphasise that extent of LGE by CMR may have value for optimising current predictive models for clinical events or mortality in patients with NICM.

Prognostic value of myocardial strain by magnetic resonance imaging in nonischemic dilated cardiomyopathy: a systematic review and meta-analysis.

Aim    This study was aimed at performing a systematic review and meta-analysis to investigate the prognostic role of left ventricular (LV) myocardial strain variables as determined by magnetic-resonance imaging in non-ischemic dilated cardiomyopathy.Material and methods    A search was performed in PubMed (MEDLINE), Google Scholar, and EMBASE databases for studies on the prognostic role of LV myocardial strain based on MR feature-tracking in non-ischemic dilated cardiomyopathy. Uncorrected odds ratio (OR) values reported by the studies where similar evaluation criteria of myocardial strain were available, were combined for a meta-analysis.Results    Nine studies were selected from 351 publications for this systematic review and meta-analysis. The analysis included a totality of 2139 patients (mean age, 52.3 years; mean follow-up duration, 42.5 months). The meta-analysis showed that the worsening of the LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) was associated with increased risk of major adverse cardiovascular events (MACE): OR, 1.13  per each % of GLS; 95 % CI: 1.050-1.225; p=0.001; OR, 1.16 per each % of GCS; 95 % CI: 1.107-1.213; p<0.0001; OR, 0.95 per each % of GRS; 95 % CI: 0.92-0.97; p<0.0001.Conclusion    The LV GLS, GCS, and GRS variables by MR feature-tracking data are powerful predictors for the development of MACE. Evaluation of myocardial strain can be used as an effective instrument for risk stratification in patients with non-ischemic dilated cardiomyopathy.

[Mechanisms of development of side effects and drug resistance to asparaginase and ways to overcome them]. / Mekhanizmy razvitiia pobochnykh éffektov i lekarstvennoi ustoichivosti k asparaginazam i puti ikh preodoleniia.

Asparaginase is one of the most important chemotherapeutic agents against acute lymphoblastic leukemia, the most common form of blood cancer. To date, both asparaginases from E. coli and Dickeya dadantii (formerly known as Erwinia chrysanthemi), used in hematology, induce chemoresistance in cancer cells and side effects in the form of hypersensitivity of immune reactions. Leukemic cells may be resistant to asparaginase due to the increased activity of asparagine synthetase and other mechanisms associated with resistance to asparaginase. Therefore, the search for new sources of L-asparaginases with improved pharmacological properties remains a promising and prospective study. This article discusses the mechanisms of development of resistance and drug resistance to L-asparaginase, as well as possible ways to overcome them.

Subacute and chronic post-covid myoendocarditis: clinical presentation, role of coronavirus persistence and autoimmune mechanisms.

Aim    To study clinical features of myoendocarditis and its possible mechanisms, including persistence of SARS-Cov-2 in the myocardium, in the long-term period following COVID-19.Material and methods    This cohort, prospective study included 15 patients aged 47.8±13.4 years (8 men) with post-COVID myocarditis. The COVID-19 diagnosis was confirmed for all patients. Median time to seeking medical care after COVID-19 was 4 [3; 7] months. The diagnosis of myocarditis was confirmed by magnetic resonance imaging (MRI) of the heart (n=10) and by endomyocardial biopsy of the right ventricle (n=6). The virus was detected in the myocardium with PCR; immunohistochemical (IHC) study with antibody to SARS-Cov-2 was performed; anticardiac antibody level was measured; and echocardiography and Holter monitoring were performed. Hemodynamically significant coronary atherosclerosis was excluded for all patients older than 40 years.Results    All patients showed a clear connection between the emergence or exacerbation of cardiac symptoms and COVID-19. 11 patients did not have any signs of heart disease before COVID-19; 4 patients had previously had moderate arrhythmia or heart failure (HF) without myocarditis. Symptoms of myocarditis emerged at 1-5 months following COVID-19. MRI revealed typical late gadolinium accumulation, signs of hyperemia, and one case of edema. The level of anticardiac antibodies was increased 3-4 times in 73 % больных. Two major clinical variants of post-COVID myocarditis were observed. 1. Arrhythmic (n=6), with newly developed extrasystole or atrial fibrillation without systolic dysfunction. 2. Decompensated variant with systolic dysfunction and biventricular HF (n=9). Mean left ventricular ejection fraction was 34.1±7.8 %, and left ventricular end-diastolic dimension was 5.8±0.7 cm. In one case, myocarditis was associated with signs of IgG4­negative aortitis. SARS-Cov-2 RNA was found in 5 of 6 biopsy samples of the myocardium. The longest duration of SARS-Cov-2 persistence in the myocardium was 9 months following COVID-19. By using antibody to the Spike antigen and nucleocapsid, SARS-Cov-2 was detected in cardiomyocytes, endothelium, and macrophages. Five patients were diagnosed with lymphocytic myocarditis; one with giant-cell myocarditis; three patients had signs of endocarditis (infectious, lymphocytic with mural thrombosis).Conclusion    Subacute/chronic post-COVID myocarditis with isolated arrhythmias or systolic dysfunction is characterized by long-term (up to 9 months) persistence of SARS-Cov-2 in the myocardium in combination with a high immune activity. Endocarditis can manifest either as infectious or as nonbacterial thromboendocarditis. A possibility of using corticosteroids and anticoagulants in the treatment of post-COVID myoendocarditis should be studied.

Study of the Osteoindictive Properties of Protein-Modified Polylactide Scaffolds.

Bone marrow mesenchymal stromal cells are multipotent and can differentiate into cells of various tissues, which determines their high importance for clinical application. We performed an in vitro study of the osteogenic potential of mesenchymal stromal cells cultured on intact polylactide scaffolds or scaffolds modified with collagen I or fibrin. Scanning electron microscopy showed that the cells formed osteogenic nodules or osteogenic nodules on both intact and fibrin-modified polylactide scaffolds. Spectrophotometric detection of alkaline phosphatase activity on days 7 and 11 showed that mesenchymal stromal cell grown on intact polylactide scaffolds and on scaffolds modified with collagen type I or fibrin more intensively synthesized alkaline phosphatase than in the control (culture plastic). This dependence increases in the presence of osteogenic differentiation factors in the medium. After long-term culturing (4 weeks), the presence of calcium deposits detected by alizarin red staining confirmed the osteoinductive properties of intact and protein-modified polylactide scaffolds. These findings suggest that polylactide scaffolds and collagen I increase the osteogenic differentiation potential of mesenchymal stromal cells.

[Epicardial Fat and Atrial Fibrillation: the Role of Profibrinogenic Mediators].

BACKGROUND: Epicardial adipose tissue (EAT) has certain paracrine functions, which could be associated with proinflammatory and fibrotic changes in myocardium even in patients without structural heart disease but with atrial fibrillation (AF). PURPOSE: to evaluate interrelationship between clinical data, parameters of tissue Doppler imaging (TDI), EAT thickness estimated by magnetic resonance imaging (MRI), and biochemical markers of fibrosis and inflammation in patients with nonvalvular AF without concomitant ischemic heart disease (IHD). MATERIALS AND METHODS: We included in this study 39 AF patients without valvular pathology or IHD with normal or moderately increased left atrial (LA) dimension (mean age 50.8±13.9 years, 49 % men). The following groups were distinguished for analysis: with idiopathic AF (iAFgroup, n=21); with AF and arterial hypertension (AF+AH group, n=18); with normal (.

[Therapeutic Effects of Multipotent Mesenchymal Stromal Cells after Irradiation].

Multipotent mesenchymal stromal cells (MSC) are now considered to be a perspective multifunctional treatment option for radiation side effects. At present.a great number of sufficient evidence has been collected in favor of therapeutic effects of MSCs in acute radiation reactions. It has been shown that MSC-based products injected locally or systemically have therapeutic effects on irradiated organs and tissues. This review presents summarized experimental and clinical data about protective and regenerative effects of MSCs on different radiation-injured organs and tissues; the main probable therapeutic mechanisms of their action are also discussed.

[Quantitative Evaluation of Intracardiac Blood Flow by Left Ventricle Dynamic Anatovy Based On Exact Solutions of Non-Stationary Navier-Stocks Equations for Selforganized tornado-Like Flows of Viscous Incompresssible Fluid].

New approach to intracardiac blood flow condition analysis based on geometric parameters of left ventricle flow channel has been suggested. Parameters, that used in this method, follow from exact solutions of nonstationary Navier-Stocks equations for selforganized tornado-like flows of viscous incompressible fluid. The main advantage of this method is considering dynamic anatomy of intracardiac cavity and trabeculae relief of left ventricle streamlined surface, both registered in a common mri-process, as flow condition indicator. Calculated quantity options that characterizes blood flow condition can be use as diagnostic criterias for estimation of violation in blood circulation function which entails heart ejection reduction. Developed approach allows to clarify heart jet organization mechanism and estimate the share of the tornado-like flow self-organization in heart ejection structure.

Genetic variability of the mouse hepatoma cells MH-22a revealed by RAPD-PCR-fingerprinting under different conditions of cultivation.

AIM: to study genetic variability in clonal lines of the mouse hepatoma MH-22a and the dependence of the capability of different clonal line cells for differentiation on the amount of genetic disturbances revealed by the RAPD-PCR method. METHODS: The hepatoma MH-22a and its ten clonal lines were transplanted into subcutaneous connective tissue (SCT) and the eye anterior chamber (EAC) by injection of the cells to syngenic C3HA mice. The growth of transplants was checked in 15-20 days after transplantation. The tumors were fixed in neutral paraformaldehyde (10%), passed through ethanol of increasing concentrations, embedded in paraffin and stained by hematoxiline and eosine and Van Gisone. The genetic heterogeneity in the hepatoma cell population MH-22a and its clonal lines in vitro and in vivo was revealed by random amplified polymorphic DNA (RAPD-PCR). For the estimation of genetic variability revealed in the fingerprints was used the genetic variability index (GVI), based on the Bootstrep and Mikulinskaya's statistic programme. RESULTS: The comparative analysis of the genetic structure of the clonal line populations in vitro and in vivo has revealed that the amount of clones with the high, intermediate, and low variability is approximately the same in both cases. It was also shown that GVI in various clonal lines in vitro correlated with their vital ability: the clones yielding clone lines had the lowest GVI. The same GVI value was found in the clonal lines proliferated in the EAC regardless of their capability for differentiation. Intraclonal analysis has shown that the highest values of changes revealed on fingerprints of the amplification of DNA products do not prevent from differentiation of tumor hepatoma cells in the EAC. CONCLUSION: These data allow concluding that the mouse hepatoma cells MH-22a can preserve ability for differentiation in spite of significant changes in their genome.

Ultrastructure and phagocytic activity of rat peritoneal macrophages exposed to low temperatures in vitro.

Hypothermia affects various components of the immune system, leading to impaired immune resistance. To examine the in vitro effect of low temperature on the ultrastructure and phagocytic function of rat peritoneal macrophages, cells were incubated at 4, 10, 24, and 37 degrees C for 60 min. Subsequently, their ultrastructure and capacity to engulf latex particles and generate superoxide anions were evaluated. The results showed a close inverse relationship between incubation temperature and ultrastructural changes, i.e., the lower the temperature, the higher the number of altered cells. In addition, at lower temperatures the number of cells capable of phagocytosis was reduced; the cells engulfed fewer particles per cell and generated less superoxide anions. These findings may be relevant for explaining the increased susceptibility to bacterial infections under hypothermic conditions.

PCR-detected genome polymorphism in malignant cell growth.

In this chapter, we analyze the problem of genetic polymorphism in tumorigenesis, which determines basic capacities of tumors. The study of genome polymorphism with modified PCR methods allows the detection of various forms of polymorphism in tumor cells. This method has made it possible to determine association of DNA polymorphism with conditions of oncogenes, antioncogenes, and genes of apoptosis and with their allelic states. A special type of nonspecific DNA polymorphism that resulted from an increase in the mutation number in the cancer cell genome was discovered. This phenomenon was called the microsatellite mutator phenotype. Because the type of DNA polymorphism correlates with various biological capacities of malignant tumors and has an important prognostic significance, the analysis of DNA polymorphism in benign and malignant tumors of different histogenesis will play an important role both in theoretical studies of cancer and in oncological practice. A modified B1-PCR was used to study the genome polymorphism in the mouse tumor cells. The gain of the band 470 bp and the loss of the band 600 bp were revealed in the hepatoma cell line MH-22a as compared with liver cells of C3HA mice. The differentiation of teratocarcinoma EC F9 cells to endoderm-like cells was not accompanied by any changes in the B1-AF DNA fingerprint.

Hypothermia affects the phagocytic activity of rat peritoneal macrophages.

To examine the effect of hypothermia on the phagocytic capacity of rat peritoneal macrophages for latex particles, male Wistar rats were exposed to 4 degrees C for 8 and 72 h. While the shorter exposure to cold did not affect body temperature and macrophage function, animals exposed to 4 degrees C for 72 h showed a mean decrease of their body temperature by 1.5 degrees C. The superoxide anion production was significantly increased whereas the number of phagocytic cells decreased. In addition, the mean number of latex particles engulfed by each individual cell was lower than that of controls. Peripheral blood mononuclear cells (PBMC) of these animals showed lower mitogen response to phytohaemagglutinin (PHA), while that for concanavalin A (Con-A) remained unchanged. Peritoneal macrophages exposed in vitro to 24 degrees C for 60 min showed a decreased phagocytic capacity in comparison with macrophages kept at 37 degrees C, an observation suggesting the development of an indigenous cell defect for phagocytosis at lower temperatures. On the other hand, the effect of additional humoral factor(s) on macrophage activity, such as an increase in serum level of catecholamines and corticosterone, cannot be excluded. The results of the study may contribute to understanding the predisposition to infections during exposure to cold.

N-terminal truncated cytochrome P450 2B4: catalytic activities and reduction with alternative electron sources.

It was shown that riboflavin binds to the truncated cytochrome P450 2B4 and forms a complex with the K(d) = 26 microM. Noncovalent complex of truncated (Delta2-27) cytochrome P450 2B4 with riboflavin was essential for electron transfer realization and catalyzed the NADH-dependent and hydrogen peroxide-supported monooxygenase reactions of aminopyrine N-demethylation and aniline p-hydroxylation. Flavocytochrome molecular maquette was capable of supporting photoactivatable electron transfer and could be photoreduced and electroreduced quantitatively in the absence of pyridine nucleotides.

The effect of interferon on mouse myocardial capillaries: an ultrastructural study.

BACKGROUND: Cardiotoxicity, including ischemia and myocardial infarction, is one of the complications observed after treatment with interferon (IFN). Therefore, the question has been raised whether IFN may cause damage to the small myocardial blood vessels. METHODS: In this study, 400 U of IFN-alpha-2b per g of body weight were injected intraperitoneally into 2 groups of C57 B1 mice, 5 days a week for 3 and 5 months, respectively. Thin sections of the myocardium were examined with a transmission electron microscope and the ultrastructure of the capillaries was compared with that of control animals. RESULTS: The results showed a statistically significant increase in the thickness of the endothelial processes of the myocardial capillary walls in the mice treated with IFN, with a subsequent decrease in the size of the capillary lumen. The entire capillary area was not affected. CONCLUSIONS: These findings may serve as an additional explanation for the cardiac complications observed in patients treated with IFN.

Effect of sodium thiopentone anesthesia on the phagocytic activity of rat peritoneal macrophages.

To elucidate the effect of sodium thiopentone anesthesia on the function of phagocytic cells, albino rats were anesthetized with 60 mg/kg. of sodium thiopentone. After 90 min., peritoneal macrophages were harvested and their capacity for superoxide anion generation was detected. Following anesthesia for 90 min. latex particles were injected intraperitoneally, and after additional 30 min. the macrophages were derived, embedded in agar and the number of cells engaged in phagocytosis, as well as the number of latex particles engulfed by each individual cell were counted in semi-thick sections. Macrophages of anesthetized animals showed a statistically significant decrease of both superoxide anion generation and mean number of phagocytic cells, and engulfed fewer particles than those of the controls. Similar results were obtained following incubation of the cells with sodium thiopentone in vitro. The serum corticosterone level in anesthetized rats was significantly higher than that of the control animals. The results indicate that impaired phagocytosis following anesthesia induced by sodium thiopentone, in addition to alterations of the immune system caused by surgical trauma, may be one of the reasons for increased susceptibility to infections of surgical patients during the postoperative period.

Effect of three days starvation on the phagocytic activity of rat peritoneal macrophages.

To examine the effect of starvation on the phagocytic activity of rat peritoneal macrophages, 8 animals were kept for 3 days on water supply only. The cells showed an increased capacity for superoxide anion production and a marked decrease in their ability to engulf latex particles. The corticosterone level of the fasting animals was markedly increased, an observation suggesting that the alteration of macrophage function could be hormonally mediated. The findings in the present study indicate that the decreased phagocytic capacity of peritoneal macrophages following starvation may be one of the factors responsible for the increased susceptibility to infections in malnourished individuals.

Ultrastructural observations on the cells of a patient with Fanconi's anemia transforming to acute leukemia.

The ultrastructural findings in the bone marrow and peripheral blood cells of a patient with Fanconi's anemia transforming to acute myelo-monocytic leukemia are presented. They consisted of an unusual large number of nuclear pockets, bridges and appendices observed in the nuclei of the polymorphonuclear cells, monocytes and to a lesser extent in the mature normoblasts. Since the mother and two younger brothers of the propositus were found to have macrocytic anemia and pancytopenia, most probably Fanconi's anemia, their peripheral blood cells were also examined with the electron microscope. The cells of all of them showed similar nuclear alterations, although in lesser quantity. The possibility that these findings are consistent with the diagnosis of Fanconi's anemia, or they herald an evolution of the disease to acute leukemia is considered.

Ultrastructural observations on bone marrow cells of 26 patients with myelodysplastic syndromes.

Bone marrow aspirates from 26 patients with myelodysplastic syndrome (MDS) were examined using transmission electron microscopy. The red blood cell precursors in 9 patients showed varying degrees of dyserythropoiesis including the presence of 2 or more nuclei, nuclei with bizarre shape and iron deposits in the mitochondria. The myeloid series showed a tendency to hypogranulation (5 patients) and in 2 patients there were signs of platelet phagocytosis. The monocytes had a normal ultrastructure except for one patient with chronic myelomonocytic leukemia (CMML) with transformation to acute myelo-monocytic leukemia (AMML). In this case, the monocytes were immature, with markedly convoluted nuclei and scanty heterochromatin. The lymphocytes also had a normal appearance, except for one patient in whom the lymphocytes were immature, with lobulated nuclei and suggested transformation of MDS to acute lymphoblastic leukemia. The plasma cells in 3 patients were slightly increased in number and in one of them Russell bodies were seen both in the cytoplasm and the nucleus. The megakaryocytic series showed a shift to the left and in one patient there were signs of emperipolesis. The alterations in the hematopoietic cells in patients with MDS described in the present study indicate that the electron microscope may supplement light microscopic findings and help in the establishment of a correct diagnosis. This may be also evident in those cases of MDS in which the very early stages of leukemic transformation cannot be easily detected by light microscopy.

Ultrastructure of human colostral cells.

The ultrastructural architecture of colostral cells of mothers of pre- and full-term infants is described. The polymorphonuclears were engaged in vivid phagocytosis of fat droplets. Similar findings were observed on the macrophages. The lymphocytes appeared normal in size and ultrastructure. A small number of eosinophils and basophils were also detected. The number of colostral cells was higher in the colostrum of mothers of preterm newborns. The number of the cells in the colostrum in mothers of both groups decreased with advancement of lactation.