[Particularities of arterial stiffness dynamics on the background of breast cancer chemotherapy].

BACKGROUND: Modern breast cancer chemotherapy regimens (BC) consider individual patient parameters and ranges of cardiotoxic doses. However, clinicians often record clinical and laboratory-instrumental signs of cardio- and vasculotoxicity in patients, which emphasizes the high importance of searching for markers of early toxic response. AIM: To study the characteristics of the response of arterial stiffness on the background of anthracycline-containing chemotherapy to determine potential markers of vasculotoxicity in BC patients. MATERIALS AND METHODS: 20 women with a BC were included. The patients received 4 cycles of chemotherapy in the doxorubicin + cyclophosphane (AC) regimen with an interval of 2-3 weeks, then they were injected with paclitaxel weekly for 12 injections, or docetaxel once every 3 weeks. All patients underwent TTE, arterial stiffness determination by the "gold standard" method and using volumetric sphygmography before the start of treatment, after the completion of the anthracycline component and after the end of taxanes. RESULTS: The average age of the patients was 45.5±5.31 years. After completing the course of anthracyclines, there was a significant increase in heart rate (from 65.6±9.3 to 73.3±10.1 beats/min.), a decrease in SBP (from 122.6±9.9 to 116.5±12.3 mmHg) and DBP (from 78.9±8.5 to 76.2±8.6 mmHg), a decrease in carotid femoral pulse wave velocity (cfPWV) (from 9.32±1.41 to 7.85±1.57 m/s), CAVI index on the left (from 6.78±0.81 to 6.5±0.88), the velocity of the cardio-ankle pulse wave on the right and left (from 6.7±0.6 to 6.5±0.7 m/s; from 7.0±0.6 to 6.3±0.8 m/sc, respectively). After the completion of the taxane, there was a tendency to increase these indicators, however, they remained significantly lower compared to the values before the start of treatment. CONCLUSION: A comparative analysis of arterial stiffness indicators at different stages of chemotherapy showed a more pronounced reaction of cfPWV, CAVI, cardio-ankle pulse wave to the administration of anthracyclines, which presumably may be associated with concomitant hemodynamic restructuring.

[Arterial stiffness in patients with acute cerebrovascular accident]. / Zhestkost' arterial'noi stenki u bol'nykh s ishemicheskimi narusheniyami mozgovogo krovoobrashcheniya.

OBJECTIVE: To identify correlations between parameters of vascular stiffness and characteristics of the clinical course of acute cerebrovascular accident (stroke). MATERIAL AND METHODS: Two hundred and seven patients with stroke (mean age 64.6±10.9 years; 115 men) treated in a neurological department of «Municipal Clinical Hospital Br. Bakhrushins of the Health Care Department of Moscow¼ were studied. All patients underwent a standard neurological and clinical-instrumental examination, including assessment of arterial stiffness by sphygmography. Analysis of the data was carried out depending on the severity of stroke and the pathogenetic subtype of stroke. RESULTS: The pathological value of the CAVI was detected in all patients with cerebral infarction. The highest values were noted in patients with an atherothrombotic subtype of stroke. A positive correlation was revealed between CAVI and the age of patients (r=0.57; p=0.0001), left ventricular myocardial mass index (r=0.55; p=0.0001), NIHSS score (r=0.6; p=0.0001) The inverse correlation was found between CAVI and glomerular filtration rate (r= -0.4; p=0.02). CONCLUSIONS: The factors determining the severity of stroke are age, arterial hypertension, type 2 diabetes, carotid atherosclerosis, left ventricular remodeling, and decreased glomerular filtration rate. The CAV and the toe-brachial index, rather than the ankle-brachial index, significantly distinguished patients with ischemic stroke from patients with transient ischemic attack.

[The Case of Fulminant Myocarditis].

Fulminant myocarditis (FM) is a severe form of inflammatory myocardial injury rapidly developing as acute heart failure, cardiogenic shock, or life-threatening disturbances of cardiac rhythm. FM requires intensive treatment including drug therapy, mechanical circulatory support, and in some cases - heart transplantation. Echocardiography can be used as a screening method of diagnostics. Magnetic resonance imaging of the heart often cannot be performed because of hemodynamic instability of a patient, therefore endomyocardial biopsy with histological and immunohistochemical studies as well as molecular-genetic analysis of obtained samples is required for final diagnosis. Prognosis of the disease is determined by histological picture. In most cases, after cessation of acute stage of the inflammatory process, FM has a favorable long-term prognosis. In this article we present a clinical case of FM and review of current literature on diagnosis and treatment of this disease.

[Creation of a statistical model for prediction of Hodgkin's lymphoma in young adults].

The aim of this study was to create a multi-dimensional correlation matrix of determinants giving information on the degree of influence on survival of young adults with Hodgkin's lymphoma each variable as well as the effect of the interaction of these variables with each other. 87 patients with Hodgkin's lymphoma at the age of 19 to 29 years (mean age 24 ± 4 years) were included in the study. Multiple matrix containing the coefficients of correlation of survival and correlation coefficients of 35 analyzed factors was of 5 significant determinants (volume of tumor lesion, stage IV of disease, E-damage, accelerated erythrocyte sedimentation rate, leukocytosis). Construction of the correlation matrix in order to select factors to be included in the equation, which contained the pair correlation coefficients of overall survival and each of factors, showed that only the volume of tumor lesion (correlation coefficient 0.2570, p = 0.026) influences on sign-result. Multiple regression equation is represented as follows ȳ=0,166667-0,227273x[volume]; R2=0,0643674507. This equation allows for given values of the factor «volume of tumor lesion" to have theoretical values of resultant sign (survival), substituting the actual values of the factor in it.

[Obesity in metabolic syndrome, as well as kidney dysfunction]. / Ozhirenie pri metabolicheskom sindrome i pochechnaia disfunktsiia.

The presence of metabolic syndrome (MS) in a patient allows him to be assigned to a group at high risk for atherosclerosis, cardiovascular events, coronary heart disease, and type 2 diabetes mellitus. In addition, MS negatively affects not only the heart and vessels, but also kidney function, which leads to chronic kidney disease (CKD). MS is pathogenetically associated with CKD and is an independent prognostic factor of the development of the latter, namely, the involvement of the kidney frequently determines prognosis and quality of life in these patients. The paper gives a modern view on the concept of MS and CKD and considers its main diagnostic criteria, etiology, and pathogenesis. The study of the relationships between MS and CKD may suggest that the high prevalence of kidney dysfunction in the general population is largely determined by metabolic nephropathies, including obesity-related nephropathy. The identification of risk factors and poor prognostic markers in this category of patients seems to be extremely important for the early diagnosis of the disease and their timely elimination is one of the main approaches to the comprehensive prevention of CKD in these patients.

[Problems in the system of state regulation of chemical safety].

In the paper the analysis of the problems of chemical safety abroad and in Russian Federation is presented, possible ways for their solutions, including the need for legal and scientific-methodical support for population health risk assessment are considered.

[The impact of anemia on content and physical chemical characteristics of membranes of erythrocytes in pregnant women].

The article deals with the study of deformability of erythrocytes, lipid protein content and physical chemical characteristics was cytoplasmic membrane of erythrocytes in women aged 21-26 years with pregnancy taking normal course and complicated with anemia. In women with pregnancy complicated with anemia, by the period of 32-34 weeks in membranes of erythrocytes the percentage of lysophosphatids and cholesterol is decreased while the number of whole phospholipids and phosphatidyl inositols is decreased. The variance analysis demonstrated that the percentage of impact of anemia on the content of whole phospholipids consisted 11.1% and on ratio of phospholipids and cholesterol about 23.9%. The changes in content of membranes of erythrocytes had no impact on their physical chemical characteristics and deformability of erythrocytes.

[Relationship between the structure-functional state of the heart and brain natriuretic peptide level in patients with arterial hypertension].

We studied relationship between structure-functional parameters of left and right cardiac chambers and N-terminal pro-brain natriuretic peptide (NT-proBNP) level in 118 patients with arterial hypertension (AH) (35 men, 83 women) and 17 healthy volunteers. Methods comprised 24-hour arterial pressure monitoring (APM), two-dimensional echocardiography (echoCG), Doppler echoCG, and tissue echoCG of mitral and tricuspid atrioventricular annuli, treadmill test, 6-min walk test, and measurement of NT-proBNP level in blood plasma. In patients with AH blood plasma NT-proBNP level was significantly higher than in a group of healthy persons of similar age. Elevation of this biochemical marker was accompanied by significant change of characteristics of remodeling of left and right parts of the heart, abnormalities of left ventricular diastolic function according to transmitral blood flow, disturbances of left ventricular diastolic and systolic function according to tissue Doplerography data. Comparative analysis of structure-functional parameters of the heart and NT-proBNP level in patients with AH allowed to reveal more significant changes of parameters of diastolic and systolic remodeling, local and global diastolic and systolic left ventricular function in patients with NT-proBNP levels more than 306 mol/ml. Factors determining NT-proBNP level in patients with AH were age, free right ventricular wall thickness, and body mass index.

[Genetic analysis of the Hsm3 protein domain structure in yeast Saccharomyces cerevisiae].

Gene HSM3 encodes the Hsm3 protein involved in the minor branch in the system responsible for the correction of mismatched bases in DNA structure and controls replicative and reparative spontaneous mutagenesis in yeast Saccharomyces cerevisiae. Spontaneous and UV-induced mutagenesis was studied in three mutant alleles of gene HSM3, and repair effectivity of artificial heteroduplexes was assessed in DNA molecule. The resuts of these studies allowed establishment of the protein domain structure of protein Hsm3 and functions of each domain: the N-terminal domain is responsible for binding to mispaired bases, and the C-terminal domain ensures the interaction with other proteins involved in the system of mismatched base correction.

[Morphometric and cytogenetic characteristics of haploid tomato plants]. / Morfometricheskaia tsitogeneticheskaia kharakteristika gaploidov tomata.

Stable differences have been found between haploid and diploid Mikado tomato plants with respect to quantitative characteristics of their vegetative and generative organs, whereas these plants were phenotypically similar with respect to qualitative characteristics, such as the bush habitus and the shapes of leaves, flowers, and fruit. A simple indirect method based on counting the chloroplasts in guard cells has been suggested to diagnose haploids. Analysis of meiosis during microspore formation in haploids has revealed considerable anomalies leading to heterogeneity and a high sterility rate of pollen, which has been confirmed by differences in DNA content. The data obtained suggest that formation of fertile gametes is accounted for by the absence of reduction division. It has been hypothesized that meiosis in haploids induces the genotypic variation that is subject to selection.

Transforming growth factor-beta 1 and ascorbate regulate proliferation of cultured smooth muscle cells by independent mechanisms.

We previously reported that ascorbate (vitamin C) can regulate the growth of cultured vascular smooth muscle cells (VSMC) directly as well as by altering the properties of extracellular matrix (ECM) [Mol Cell Cardiol 1997;29:3293-303]. In the present study we compared the effects of ascorbate and transforming growth factor-beta 1 (TGF-beta1) on VSMC growth in order to determine whether their actions were mediated by similar mechanisms. When VSMC proliferation was stimulated by fetal bovine serum, the addition of TGF-beta1 (20 ng/ml) or ascorbate (1 mM) to the cell culture medium inhibited the cellular incorporation of [3H]thymidine by 19 and 59%, respectively, and by 85% when added together. The cell growth inhibitory effects of TGF-beta1 and ascorbate were partially mediated by changing the growth-regulatory properties of the ECM produced by the cells. Thus, VSMC grew more slowly on ECM deposited by VSMC under treatment with 20 ng/ml TGF-beta1 or 1 mM ascorbate (52 and 46% inhibition, respectively) than on control ECM, and their combination had an additional inhibitory effect (84%). Anti-TGF-beta1 neutralizing antibodies prevented the direct and ECM-mediated effects of TGF-beta1 on VSMC growth, but did not alter the effects of ascorbate. When ECM was pre-incubated with increasing concentrations of TGF-beta1, the growth rate of freshly plated VSMC gradually decreased, indicating that ECM-bound TGF-beta1 retained its biological activity. Comparison of the patterns of TGF-betal binding to ECM produced by VSMC in the presence or absence of ascorbate revealed no significant differences. Extraction of ECM-bound TGF-beta1 by incubation of exposed ECM with plasmin did not affect the ECM-mediated inhibitory effect of ascorbate, as the rate of proliferation of secondary VSMC cultures grown on ascorbate-dependent and independent matrices treated with plasmin were equally increased. These results suggest that the amount of ECM-bound TGF-beta1 was not altered by ascorbate. The secretion of TGF-beta1 into the cell culture medium by VSMC also did not depend on the ascorbate supply. Finally, addition of heparin to the VSMC culture medium during ECM production abolished the ECM-mediated growth inhibitory effects of ascorbate, but did not affect the action of TGF-beta1. Our data demonstrate that the growth inhibitory effects of ascorbate on cultured VSMC are independent of the action of TGF-beta1, and the effects of these two compounds on VSMC growth are additive.

Ascorbate affects proliferation of guinea-pig vascular smooth muscle cells by direct and extracellular matrix-mediated effects.

Proliferation of smooth muscle cells and deposition of extracellular matrix proteins are important events in the formation of atherosclerotic plaques. We have investigated the direct and matrix-mediated effects of ascorbate on the proliferation rate of vascular smooth muscle cells (VSMC) isolated from the guinea-pig aorta. In the presence of ascorbate, cells showed a bi-phasic growth pattern. At 125 microM ascorbate, -3H--thymidine incorporation was stimulated 25%. However, higher concentrations of ascorbate gradually decreased cell-incorporated radioactivity up to 50% at 2 mM ascorbate. These effects of ascorbate on DNA synthesis in VSMC were paralleled by the changes in cell number and were not due to ascorbate cytotoxicity. Alpha-tocopherol (0.1 mM), individually and in combinations with 1 mm ascorbate, also inhibited DNA synthesis in VSMC. Ascorbate also influenced proliferation of smooth muscle cells through matrix-mediated effect. New VSMC culture plated on extracellular matrices deposited by smooth muscle cells in the presence of 0.1-1 mM ascorbate had up to 50% lower proliferation rate than on matrices from ascorbate-deficient cells, as assessed by [3H]-thymidine incorporation. This effect was independent from alpha-tocopherol and specific inhibitors of collagen synthesis: L-azetidine-2-carboxylic acid and pyridine-2,4-dicarboxylic acid. An ascorbate-dependent matrix effect was specific for smooth muscle cells grown on VSMC and human skin fibroblast-originated matrices, but not for human vascular endothelial cells. The possible involvement of ascorbate in the regulation of smooth muscle cells proliferation by its antioxidant/pro-oxidant effects and regulation of extracellular matrix composition are discussed.

An investigation of the effect of antisense RNA gene on bovine leukaemia virus reproduction in cell culture.

A possible approach to control of bovine lymphoproliferative disease caused by bovine leukaemia virus (BLV) may be the development of an "antiviral information immunity" based on the effect of anti-sense RNA (asRNA). A numbers of constructs were obtained, under control of various promotors (herpesvirus thymidine kinase, T-antigen SV40 promoter), carrying as DNA against gene X, the expression product of which is a transactivator of viral transcription from the BLV LTR promotor. As a model system for the analysis of antiviral activity of constructs developed, cloned continuous cell lines of BLV-producing FLK cells were used. The level of BLV expression in cells transfected with the constructs was determined by various parameters. Differences were detected in different clones obtained from non-transfected cells, as well as variation between transfected clones, as measured by reverse transcriptase, competitive radio-immunoassay for BLV p24, the viral particle count on agar membrane, and the tumorigenicity for nude mice. The differences in inhibition of expression of BLV genes and their products may be explained in terms of the site of integration of asDNA and the number of integrated copies.