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Proceedings of the National Academy of Sciences of Belarus, Medical series

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Vol 20, No 2 (2023)
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https://doi.org/10.29235/1814-6023-2023-20-2

CLINICAL AND EXPERIMENTAL MEDICINE 

95-105 301
Abstract

Natriuretic peptides (NUPs) are the strongest predictors of poor prognosis in patients with heart failure (HF). Single-nucleotide polymorphisms (SNPs) rs198389 of the NPPB gene and rs5068 of the NPPA gene are associated with altered levels of NUP. The role of candidate gene polymorphisms in the activity of the NUP system and the association of NPPA/ NPPB SNPs with the risk of cardiovascular disease (CVD) in individuals with HF and atrial fibrillation (AF) is not well understood.

The study aims to evaluate the allele and genotype frequencies of NPPA rs5068 and NPPB rs198389 SNPs in a selective sample of the Belarusian population, to determine the relationship of these SNPs with NUP concentrations, and to assess the prognostic significance of these SNPs on the risk of HF hospitalization in patients with HF and permanent AF.

The study involved 187 patients. The main group included 152 patients with HF with left ventricular ejection fraction (LVEF) < 50 %. Group 1 included 48 patients with HF and AF; group 2 – 51 patients with HF and sinus rhythm (SR) and 35 patients in the control group. The levels of atrial and brain natriuretic peptides (ANP and BNP) and the N-terminal fragment of the brain natriuretic peptide (NT-proBNP) were determined. A genetic testing of polymorphic loci of the rs5068 NPPA gene and the rs198389 NPPB gene was performed. The primary endpoint of the study was hospitalization due to HF progression.

The average observation period was 12.1 [from 9 to 14] months. The distribution of the genotype and allele frequencies of rs198389 NPPB and rs5068 NPPA in HF patients with LVEF < 50 % is comparable to that in individuals without CVD. In patients with HF and persistent AF, the minor allele C rs198389 NPPB is associated with higher BNP levels compared to patients with HF and SR (542 [333.7; 909.4] pg/ml versus 247.3 [244; 365.2] pg/ml; p < 0.05), but it has no relationship with the NT-proBNP level. In patients with HF and permanent AF, the ANP levels are not associated with rs5068 NPPA.

The frequency of the T allele rs198389 NPPB in hospitalized patients was significantly lower compared to patients who were not hospitalized (22 patients (44 %) versus 83 patients (62 %); p = 0.04). The presence of the C allele rs198389 NPPB was associated with a higher risk of HF progression in patients with HF and AF, the odds ratio (OR) = 2.071 [95 % CI from 1.072 to 4.001], p < 0.05.

106-111 1156
Abstract

Dental ectopia is a rare developing anomaly characterized by a change in the normal eruption pathway of a deciduous, permanent or supernumerary tooth. In some cases, ectopic teeth are present in the non-dentate area like maxillary sinus. The article presents cone beam computed tomography data of 7 asymptomatic patients with teeth totally or partially located inside the maxillary sinus. Dentigerous cysts and odontomas can cause displacement of impacted teeth into ectopic positions.

112-125 208
Abstract

Stage III non-small cell lung cancer (NSCLC) is a heterogeneous group of tumors. The prognosis for patients with stage III NSCLC remains poor, and the 5-year survival rate is not more than 20 %. Therefore, an actual problem is to develop prognostic indicators that would allow predicting the progression of the tumor process in patients in order to correctly build strategy and tactics for their treatment.

The objective of the study was to clarify and substantiate the possibility of using laboratory parameters characterizing the level of blood proteins – participants in carcinogenesis in predicting the NSCLC progression in patients with stage III disease.

In 1187 patients who were first diagnosed with stage III NSCLC, the duration of the relapse-free period after treatment was analyzed using the observation results for one year. The mean age of patients was 63 ± 23 years. In 89 patients (58 ± 23.5 years), the concentration of CYFRA 21-1, SCC, TPA were determined by electrochemiluminescent method; pyruvate kinase M2, CXCL5, CXCL8 chemokines – by enzyme immunoassay; CXCR1 and CXCR2 receptors– by flow cytometry.

A proportional hazards model was used to identify potentially informative indicators for predicting the duration of the relapse-free period in patients with stage III NSCLC: the levels of lymphocytes containing CXCR1 and CYFRA 21-1. Based on the one-year observation results and the graphical analysis of Kaplan-Meier, groups of low (T1N2M0, T3N1M0, T2N2M0, T4N0M0, T3N2M0) and high (T1N3M0, T2N3M0, T3N3M0, T4N1M0, T4N2M0, T4N3M0) risk of tumor progression were identified. High-risk patients had a higher level of CYFRA 21-1, a relative content of the receptor CXCR1 in lymphocytes, and a relative content of the receptor CXCR2 in monocytes compared to low-risk patients (p < 0.05). With their participation, based on the results of logistic regression analysis, an equation was constructed, the calculation of which makes it possible to predict the risk of tumor recurrence. The threshold value of the equation is 0.519. The sensitivity of the prediction model was 80.9 %, the specificity was 83.3 %, and the prediction value of a positive result was 84.4 % and that of a negative result – 79.6 %. The study results give grounds to recommend a set of laboratory parameters in the blood of stage III NSCLC patients, including the CYFRA 21-1 level and the receptors CXCR1 and CXCR2, in order to assess their tumor progression risk.>< 0.05). With their participation, based on the results of logistic regression analysis, an equation was constructed, the calculation of which makes it possible to predict the risk of tumor recurrence. The threshold value of the equation is 0.519. The sensitivity of the prediction model was 80.9 %, the specificity was 83.3 %, and the prediction value of a positive result was 84.4 % and that of a negative result – 79.6 %.

The study results give grounds to recommend a set of laboratory parameters in the blood of stage III NSCLC patients, including the CYFRA 21-1 level and the receptors CXCR1 and CXCR2, in order to assess their tumor progression risk.

126-139 1019
Abstract

Among tumors of the gastrointestinal tract, the incidence and mortality from primary liver cancer remains high. Over the past 20 years, the incidence of liver cancer in Belarus has increased by 45.7 %. 

The aim of the study was to establish the relationship between the expression of the NF1, p53, bcl-2 proteins and the pRB genes with DNA/RNA of viruses and mutations of the BRCA 1/2 and hMSH2 genes in liver cancer.

Patients (n = 303) with morphologically established primary liver cancer were examined. A molecular biological and immunological study was performed: antibodies to cell-cycle NF1, p53, bcl-2, pRB proteins, DNA/RNA of viruses, the BRCA 1/2, hMSH2 gene. The levels of antibodies to p53, bcl-2, pRB, and NF1 in the serum of healthy individuals differed from those in blood samples and tissue extracts from patients with hepatitis C, liver cancer and in native liver tissue samples. Mutations in liver cancer were (p = 0.004): in the tumor tissue – 6.13 %, in the blood – 0.85 %. Changes in the hMSH2 gene in the tissue were set at 15.48 %. DNA/RNA was isolated in the tumor tissue: HSV 1/2 – 56.1 %, HHV6 – 24.4, CMV – 17.1, HCV – 17.1, HBV – 4.9, HPV – 4.1, VEB – 2.4 %. Including mixed persistence – 26.8 %. In hepatitis (C, B) and liver cancer with CMV carriers, the expression of bcl-2, NF1 and pRb1 (p = 0.001) increases. The Epstein–Barr virus leads to the activity of the p53 protein in liver cancer (p = 0.003). The p53, bcl-2, pRB, and NF1 proteins in the liver tissue do not depend on the age and sex of patients. The degree of their influence on the function of genes with regard to DNA/RNA of viruses and mutations present in the genome (BRCA 1/2, hMSH2) suggests the degree of oncogenicity of viruses. The concentrations of p53, bcl-2, pRB, and NF1 in the blood, exceeding the predicted ones, for 50.8 year old persons, indicate the risk of development/presence of a tumor process in the liver. 

140-146 325
Abstract

The aim of the work was to study clinical and immunological relevance of quantification of antibodies to type I, II, III collagen and elastin in systemic scleroderma. 51 systemic scleroderma patients with verified diagnosis and different disease activity were included in the study. 30 healthy volunteers were included in the control group. The laboratory markers were assessed both on admission and on discharge. 

Antibodies to serum type I, II, or III collagen, and elastin were measured using the ELISA test with antigen immobilized on the magnetic beads. Increased concentrations of antibodies to serum type I, II, or III collagen and elastin were found in systemic scleroderma with minimal disease activity. Statistical interrelations between antibody levels and disease activities and course types were also revealed. Skin, kidney, lung, and heart involvement in systemic scleroderma patients were associated with the more pronounced levels of antibodies to collagen compared to the absence of these conditions. 

Measurement of antibodies to serum type I, II, or III collagen and elastin in systemic scleroderma using antigen immobilized on magnetic beads is a candidate biomarker for better diagnosis and assessment of disease activity, course type, clinical pattern, treatment control, as well as useful tool for research of systemic scleroderma pathogenesis. 

147-157 239
Abstract

The importance of free amino acids in the processes of vital activity in normal and pathological conditions is well known. At the same time, there are no data on the role of blood plasma valine in the formation of thyroid status, prooxidant-antioxidant state, and in the development of hyperthermia caused by bacterial endotoxin, although its participation in these processes is quite natural, since valine is an inhibitor of arginase, the activity of which affects the level of arginine amino acid and nitric monoxide (NO). This is important in the regulation of body temperature, lipidperoxidation processes, and the level of iodine-containing hormones. 

The aim of the study was to elucidate the significance of blood plasma valine and the L-arginine-NO system in the formation of thyroid status, prooxidant-antioxidant state and the maintenance of body temperature during stress caused by bacterial endotoxin. 

In experiments on rats and rabbits, it was found that under the conditions of E. сoli lipopolysaccharide action in the body of animals, the pituitary-thyroid gland system, lipid peroxidation (LPO) processes in the blood and liver activate, the nitrate/nitrite (NO3–/NO2–) content increases, the level of valine and arginine in the blood plasma decreases, and body temperature increases. Under the conditions of depression of liver arginase with L-valine (100 mg/kg intraperitoneally 30 minutes before endotoxin injection), the LPS action is not accompanied by an increase in body temperature, leads to less pronounced changes in lipid peroxidation processes, as well as to a more significant decrease in the triiodothyronine content and to an increase in the NO3–/NO2– level in blood plasma in rats. Preliminary administration of the NO synthesis inhibitor L-NAME (25 mg/kg intraperitoneally 30 minutes before endotoxin injection) into the animal body not only reduces body temperature rise and NO3–/NO2– level increase in the blood plasma when acted upon by endotoxin, but also exacerbates changes in the LPO processes in the blood plasma and liver, and prevents the activation of the pituitary-thyroid gland system. 

158-167 258
Abstract

Early diagnostics of resistance to fluoroquinolones facilitates early start of adequate therapy and increases the chance of a favorable outcome of the tuberculosis. Application of genetic methods permits to obtain within 1–2 days the results of Mycobacterium tuberculosis resistance detection to anti-tuberculosis drugs, unlike the classical methods requiring up to 1−2 month.

The aim of the study is to develop a method for the M. tuberculosis identification and detection of point mutations in codons 90, 91, 94 of the gyrA gene associated with the resistance to fluoroquinolones.

There were 88 cultures of mycobacteria studied: M. tuberculosis (n = 81), M. tuberculosis H37Rv, M. chelonae (n = 1), M. gordonae (n = 1), M. fortuitum (n = 1), and other three isolates of non-tuberculosis mycobacteria isolated from patients in the Republican Scientific and Practical Center for Pulmonology and Phthisiatry. The types of mutations in the gyrA gene were studied by the standard GenoTypeMTBDRsl method (HAIN, Germany), Sanger sequencing, and by the developed real-time PCR method. Based on the analysis of mutations in the gyrA gene in 78 isolates of M. tuberculosis, the dominant mutations were found to be mutations Asp94Gly and Ala90Val, which were identified in 21 and 27 isolates correspondingly: they accounted for 64 % of all mutations. M. tuberculosis also harbored mutations p.ASP94ALA and p.ASP94TYR/HIS in 6 (8.0 %) and 9 (12.0 %) isolates, respectively. One strain harbored a mutation at triplet 88 and one strain had a double mutation (p.ALA90VAL and p.ASP94GLY). The developed real-time PCR method demonstrated a high frequency of coincidence of results with the phenotypic determination of resistance to ofloxacin and the results testing by the standard GenoTypeMTBDRsl method and sequencing.

The developed method is accomplished to identify M. tuberculosis, and discriminate mutations p.ALA90VAL, p.SER91PRO, p.ASP94ALA, p.ASP94TYR/HIS, p.ASP94GLY, p.ASP94ASN providing diagnostics of resistance to fluoroquinolones.

168-176 714
Abstract

The aim of the work was to study the morphological state of the dentition of persons with normal occlusion according to cephalometric X-ray using extraoral parameters.

A method for assessing the state of the maxillofacial system using the PoN reference line, PL line, PLV extrafacial vertical line is proposed. Schemes for determining the parameters formed on their basis are presented as well. These parameters will allow diagnosing disorders of maxillofacial system in patients with malocclusions at a higher quality level.

The average values of the proposed new parameters were determined and presented in tables using extraoral parameters in persons 7–15 years old with normal occlusion. A comparative analysis of the angular and linear indices of cephalometric images in persons 7–12 and 12–15 years old with normal occlusion showed that with age the tendency of their change is identical to traditional methods.

The proposed and studied angular and linear indices of cephalometric images in persons 7–15 years old with normal occlusion using extraoral parameters (PL line and PLV vertical line) are recommended for use in the practical work of orthodontists.



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ISSN 1814-6023 (Print)
ISSN 2524-2350 (Online)