[Postgenomic and structural changes in the myocardia of Wistar rats fed a high-salt diet].

The relationship between dietary sodium, hypertension, and cardiovascular injury is far from clear. One of the important links in this process can be microRNAs that have the ability to modulate gene expression at the post-transcriptional level. However, their role in this process has not been fully studied. In addition, further studies require the identification of structural changes in the myocardium in conditions of long-term consumption of a high-salt diet. The aim of the study was to evaluate the expression levels of nuclear transcription factor κB (NFκB), microRNA (miRNA)-21 and structural changes in the myocardium during long-term consumption of a diet containing 8% (high) sodium chloride in Wistar rats. Material and methods. 20 Wistar rats with initial body weight 280.5±42.7 g were divided into two equal groups. The high salt (HS) group received 8% NaCl in the diet, the control (NS) group received the standard diet (0.34% NaCl). After 4 months, systolic blood pressure was measured in rats using the cuff method on the tail; the myocardial mass index was assessed after dissection; histological and electron microscopic examination of the myocardium was performed, and the expression levels of miRNA-21 and NFκB in the myocardium were determined. Results and discussion. Consumption of a diet high in sodium chloride for 4 months did not significantly affect the level of systolic blood pressure in normotensive Wistar rats, but led to an increase in myocardial mass index by 25.0% (p<0.05). In the HS group, hypertrophy of cardiomyocytes and an increase in the wall thickness of arterial vessels were revealed. The area of perivascular fibrosis in rats of the HS-group was almost 1.8 fold higher than in the NS-group. In animals of HS-group, the relative levels of expression of NFκB (more than 2 times) and miRNA-21 (almost 6 times) increased compared with the control. It can be assumed that the negative impact on the cardiovascular system of high-salt diets is partially realized through NFκB-associated signaling pathways and miRNA-21 activation. Conclusion. In Wistar rats, long-term use of a high-salt diet results in myocardial remodeling that is not associated with changes in blood pressure. At the same time, the adverse effects of high salt intake on the myocardium are mediated, in particular, by postgenomic mechanisms, namely an increase in the expression levels of NFκB and microRNA-21.

Association of myocardial and serum miRNA expression patterns with the presence and extent of coronary artery disease: A cross-sectional study.

BACKGROUND: MicroRNA (miRNAs) participate in the pathogenesis of coronary artery disease (CAD). OBJECTIVE: To evaluate the expressions of myocardial and serum miRNA-27а, miRNA-133а, and miRNA-203 in CAD patients. METHOD: This cross-sectional observational study comprised 100 subjects (60.9 ± 1.0 years; 67% men). The right atrial and serum expressions of miRNA-27a, miRNA -133a, and miRNA-203 in 80 patients referred for elective coronary artery bypass graft surgery (CABG) and 20 control patients scheduled for heart valve surgery were analyzed using real-time polymerase chain reaction. RESULTS: There was a positive correlation between the SYNTAX score I index and serum miRNA-203 expression level (r = 0.693; p < .001). Patients with ≥3 coronary artery lesions had significantly higher myocardial expressions of miRNA-27a, miRNA-133а, and miRNA-203 than patients with 1-2 vessel disease in the atrial myocardium (miRNA-27a: 234.62 ± 29.51 vs. 182.39 ± 19.62 relative expression unit (REU); miRNA-133а: 127.53 ± 13.41 vs. 111.35 ± 12.31 REU; and miRNA-203: 5.25 ± 0.96 vs. 4.71 ± 0.67 REU; р < 0.05); the same association was found for serum miRNA expressions (miRNA-27a: 11.41 ± 3.85 vs. 4.82 ± 1.82 REU; miRNA-133а: 8.42 ± 2.43 vs. 4.35 ± 1.23 REU; and miRNA-203: 145.71 ± 15.73 vs. 43.70 ± 9.67 REU; р < 0.05). The decision tree method established that the risk of multivessel lesions was increased five-fold if the miRNA-203 serum expression was >101.00 REU (OR, 5.90; 95% CI, 2.34-9.46; p < .001). CONCLUSIONS: Both myocardial and serum miRNA-27а, miRNA-133а, and miRNA-203 expressions are higher in CABG patients than in non-CAD subjects. The serum miRNA-203 expression level corresponds to myocardial expression and is strongly correlated with the extent of coronary atherosclerosis.

Rare form of erdheim-chester disease presenting with isolated central skeletal lesions treated with a combination of alfa-interferon and zoledronic Acid.

Erdheim-Chester disease (ECD) represents a clonal non-Langerhans histiocytosis, which manifests under an extensive variety of clinical symptoms. This creates a challenge for the physician, who is required to recognize and diagnose the disease in the early stages. Despite this considerable challenge, in the last decade there has been a dramatic increase in ECD diagnoses, in most part due to an increasing awareness of this rare disorder. Involvement of the axial skeleton is exclusively uncommon with no official recommendations for the treatment of the bone lesions. Here, we present a case report of a young male patient with isolated lesions of the spine, ribs, and pelvis, who was successfully treated with a combination therapy of alfa-interferon and zoledronic acid.

[Use of BRAF V600E mutation in the differential diagnosis of follicular and papillary tumors of the thyroid and for the optimization of thearpy].

A possibility of detection of BRAF mutation has been studied by means of polymerase chain reaction in punctate from the thyroid node with the aim of diagnostics of high-differentiated cancer on pre-operative stage. A study includes 94 patients with nodal lesions of the thyroid. According to cytological investigation of material, received by fine-needle aspiration biopsy, papillary thyroid cancer was revealed in 47 patients, follicular tumor-in 35 and nodal colloid goiter in 12 patients. In case of papillary thyroid cancer data of genetic analysis showed the following indices of sensitivity, specificity and diagnostic accuracy: 86%, 100% and 92% correspondingly. Detection of BRAF mutation could be used in pre-operative differential diagnostics of high-differentiated cancer and benign nodal lesions of the thyroid.

[Immunological mechanisms in pathogenesis of coronary atherosclerosis].

AIM: To evaluate functional parameters of immune system in patients with different variants of ischemic heart disease (IHD): stable angina pectoris and myocardial infarction; the role of immunological disorders in pathogenesis of IHD. MATERIAL AND METHODS: Immunological investigation of 136 IHD patients (102 with stable angina and 34 with myocardial infarction) included the study of the phenotype of lymphocytes: CD3, CD4, CD8, CD16, CD19, CD11/18, CD25, CD95 and HLA-DR. Measurements were made of serum concentrations of IL-1beta, IL-2, IL-6, IL-8, TNF-alpha, rIL-2 and expression of mRNA IL-1beta, IL-2, IL-6, TGFb1 in vascular wall of patients with coronary atherosclerosis (angina pectoris, myocardial infarction). RESULTS: One of the basic mechanisms taking part in development of atherosclerosis is immune-mediated inflammation of the vascular wall. Inflammatory cytokines have a significant role in this process. The serum levels of IL-1beta, IL-2, IL-6, IL-8, TNF-alpha in patients with coronary atherosclerosis were found to be significantly higher than in healthy controls. The study of IL-1beta, IL-2, IL-6, TGFb1 in tissue revealed that radial artery wall contains mRNA of the cytokines. The main cytokine of the aorta appeared to be IL-2, and the main peripheral artery cytokines were IL-1beta, IL-6. CONCLUSION: Increased serum concentrations of IL-1beta, IL-2, IL-8 in patients with coronary atherosclerosis reflect immune-inflammatory nature of the disease. Detection of dissimilar cytokines in tissue sampling reflects not only different degree of vascular involvement in the process but also phase evolution of the disease. Coronary atherosclerosis may result in adaptive immune response.

[Immunological interactions in different forms of coronary heart disease].

The study included measurement of serum levels of IL-1beta, IL-2, IL-6, IL-8, and TNF-alpha, as well as the expression of mRNA IL-1beta, IL-2, IL-6, and TGfb1 in the vascular wall of patients with coronary atherosclerosis (angina, myocardial infarction). IL-1beta, IL-2, IL-6, IL-8, and TNF-alpha serum levels in patients with coronary atherosclerosis were found to significantly higher than those in healthy individuals (control group). Detection of IL-1beta, IL-2, IL-6, and TGFb1 in tissues revealed mRNA of the cytokines under study in radial artery wall. The main aortic cytokine was found to be IL-2 (7 samples out of 8); the main cytokines in peripheral arteries were IL-1beta and IL-6 (5 samples out of 8). The results show that elevation of IL-1beta, IL-2, and IL-8 in patients with coronary atherosclerosis demonstrates an immunoinflammatory nature of the disease; the detection of dissimilar cytokines in tissue samples reflects not only different degree of vessel involvement, but also a phase character of the process.

[Oncologic risk factors in papillomavirus infection]. / Faktory onkologicheskogo riska pri papillomavirusnoi infektsii.

Cytological screening is essential for adequate diagnosis of gynecological cancer. Moreover, every effort should be made to identify such risks of cancer as viruses (HPV, Herpes simplex, cytomegalovirus, Epstein-Barr virus, etc.). When high risk HPV-16 and HPV-18 are detected, diagnostic strategies should include assay of blood prolactin and prolactin/TTH ratio. Virus-related tumors and various risk groups may be studied using HPV genotyping detection of high-risk alleles of certain genes. Hence, some HPV gene variants and gene polymorphism can be investigated as potential risk factors in women.

[Elevated expression of argentophilic proteins from the nucleolar organizer regions in myocardium of patients with obstructive hypertrophic cardiomyopathy and mutations in p53 tumor suppressor gene]. / Povyshennaia ékspressiia argentofil'nykh belkov oblastei iadryshkovogo organizatora v miokarde bol'nykh obstruktivnoi gipertroficheskoi kardiomiopatiei i mutatsii v gene opukholevogo supressora p53.

Silver staining for nucleolar proteins was used to evaluate the ribosomal genes activity in cardiomyocytes (Cm) and fibroblast-like cells (FBS) of intraventricular septum, and other regions of the left ventricle. Specimens to be analysed were taken from 7 patients with idiopathic obstructive hypertrophic cardiomyopathy (OHCM). In this group the quantity of nucleoli and AgNORs, reflecting the transcriptional and processing level of pre-ribosomal RNA in all type of cells, was at least 2 and 3 times higher than in patients with essential hypertension and in healthy control, respectively. We suggest that nucleolar hypertrophy in patients with hypertrophic cardiomyopathies, inappropriate to hypertrophy in other pathological conditions, may be most probably of compensatory character, and this may be in part explained by nuclear hyperploidy and chromosomal endoreduplication. We have noted a marked heterogeneity in shape, size and quantity of nucleoli, and in AgNORs of FBC. Nuclei with modulated phenotype containing nucleoli of high activity were revealed. This article presents the first data on p53 mutation identification in patients with advanced OHCM.

[The role of HLA antigens in predicting the active course of multiple myeloma]. / Rol' HLA-antigenov v prognozirovanii aktivnosti techeniia mnozhestvennoi mielomy.

AIM: Detection of associations between carrying some HLA-antigens class I in patients with multiple myeloma (MM) and activity of the malignant process. MATERIALS AND METHODS: 76 MM patients received polychemotherapy. Its efficacy was assessed after one, three, six and twelve courses by reduced blood and/or urine levels of monoclonal protein, signs of bone healing, reestablishment of normal number of plasma cells in the bone marrow. Identification of HLA-antigens was made in two-stage lymphocytotoxic complement-mediated test using the standard panel of the anti-HLA sera. Data on HLA-typing of 865 blood donors served control. The findings were statistically processed. RESULTS: All the patients were divided into 3 groups: with indolent (n = 18), active (n = 25) and aggressive (n = 37) MM course. In patients with aggressive MM course high chi-square values were estimated for three HLA specificities: HLA-B13, HLA-B40, HLA-B5. Only HLA-B13 proved significant. No significant differences in carrying HLA-antigens were revealed for patients with active MM course. CONCLUSION: The survival of MM patients depends on the degree of the malignant process activity. Patients with aggressive MM course significantly more frequently carry HLA-B13, therefore it can be considered a genetic marker of MM. Its detection can serve a criterion for determination of adequate polychemotherapy.

[Tissue typing using a Soviet automated luminescent microscope-photometer]. / Tkanevoe tipirovanie na otechestvennom avtomatizirovannom liuminestsentnom mikroskope-fotometre.

Automated fluorescent microscope developed by the authors permits photometry of microquantities of cellular suspensions in scanning standard 60-well plates with a flat bottom. Automated and semiautomated modes of operation are possible. Fluorescent stains and schemes of staining the examined cells that yield stable results in the lymphocytotoxic test have been selected. Comparative analysis of the efficacies of histocompatibility antigens detection by the routine and the fluorescent technique has shown a number of advantages of the fluorescent method. Specific features of fluorescent stains used for staining live cells are described.