ORIGINAL ARTICLES
Many genetic variants associated with metabolic disorders have incomplete penetrance in human. Their phenotypic manifestation depends on the life style factors. In this work, we compared the associations of genotypes at 11 polymorphic sites with body mass index (BMI) and lipid metabolism parameters (levels of total cholesterol (TC), triglycerides, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C)) in three groups of adolescents from Novosibirsk, examined in 1999, 2009 and 2019. In each group, from 187 to 665 persons were genotyped at each site. One-way analysis of variance (independent covariates: gender and age) was used for evaluation. For rs1800497 in the ANKK1 gene, rs53576 in the OXTR gene, rs1360780 in the FKBP5 gene, and rs4680 in the COMT gene, as well as for tandem repeats in the promoter of the MAOA gene, promoter and intron 2 of the SLC6A4 gene (separately and as part of a haplotype), and 3′-untranslated region of the SLC6A3 no associations of genotypes with BMI and lipid metabolism parameters were found in any of the groups. For APOE genotype, an association was obtained with TC levels: p = 0.042 and 0.034, respectively, in the 1999 and 2009 collection groups, as well as with LDL-C: p = 0.001 and 0.002, respectively, in the 2009 and 2019 groups. Moreover, the maximum levels of TC and LDL-C were found among carriers of most common genotype ε3ε3 in 1999 group, and among carriers of atherogenic allele ε4 in other two groups. Thus, it was shown that in adolescents there was an opposite correlation of carriage of the ε4ε4 genotype for the APOE gene with the levels of total cholesterol and LDL cholesterol in the case of normal and reduced calorie intake. For rs6265 in the BDNF gene, the level of statistical significance of the association of the common C allele with TC and LDL-C levels was directly correlated with dietary caloric intake (p = 0.617 and 0.573; p = 0.049 and 0.090; p = 0.010 and 0.024, respectively, in the groups of 1999, 2009 and 2019).
One of the pressing issues of modern pharmacology remains the development of drugs with targeted antitumor action, or the creation of dosage forms of selective action of already known cytostatics in order to increase the effectiveness of chemotherapy and reduce the overall toxic effect on the body. In this work, it is proposed to use apolipoprotein A-I as a transport form of the antitumor drugs actinomycin D, doxorubicin, vinblastine and melphalan. Material and methods. Apolipoprotein A-I was isolated from the high-density lipoprotein fraction of human blood plasma. Apolipoprotein A-I was labeled with 1 % fluoresceinisothiocyanate (FITC). For the experiments, we used male C57Bl mice weighing 20–25 g. Ehrlich ascites carcinoma cells were obtained from peritoneal exudate 9–10 days after transplantation. Fluorescent analysis was carried out on an AxioImager Z1 “Zeiss” microscope using an AxioCamMRc digital camera and AxioVision V.4.5 software. The absorption spectra of antitumor drugs in the optical region of electromagnetic radiation were studied using an Evolution 300 spectrophotometer (Thermo Fisher Scientific, USA). Results. The paper presents the results indicating the ability of FITC-labeled apolipoprotein A-I to enter tumor cells. Using the method of column chromatography and spectrofluorimetry, the formation of apolipoprotein A-Icytostatic complex (actinomycin D, doxorubicin, melphalan, vinblastine) was shown. Analysis of the content of drugs in tumor cell lysates showed that absorption (internalization) was more pronounced during incubation of cells with cytostatics in complex forms with apolipoprotein A-I compared with the absorption of cytostatics by cells without a carrier. Conclusions. It has been established that apolipoprotein A-I can be a direct carrier of cytostatics into the cells of Ehrlich ascites carcinoma.
The aim of the study is to evaluate cardiac fatty acid binding protein as a prognostic biomarker for the occurrence of severe post-infarction structural and functional remodeling of the left ventricular myocardium and heart failure with clinical manifestations in patients with acute myocardial infarction during long-term follow-up. Material and methods. The study included 95 patients with acute myocardial infarction and ST-segment elevation (mean age 56.8 ± 9.8 years). Upon admission to the emergency room, all patients underwent clinical and laboratory studies to determine cardiac fatty acid binding protein (cFABP) and high-sensitivity troponin T (hs-TnT). At the end of the long-term follow-up (Me = 36 months), the patients were examined for clinically evident heart failure (NYHA functional class II and higher), high-sensitivity C-reactive protein (hsCRP) was determined in the blood, and echocardiography was performed. According to the echocardiography data, the presence and severity of structural and functional remodeling of the left ventricle myocardium (SFR LV) were established. Results. It was determined that the presence of clinically evident heart failure is directly associated with age, the Charlton comorbidity index, cFABP ≥10 ng/ml upon admission to the hospital and has a direct tendency to be associated with hs-TnT upon admission to the hospital. The presence of severe structural and functional remodeling of the left ventricle myocardium is directly associated with age, obesity, creatinine, cFABP ≥ 10 ng/ml and hs-TnT upon admission to hospital, and there is also a direct tendency towards an association with age. It was revealed that hs-TnT upon admission to hospital is directly associated with hsCRP ≥ 2 mg/l at the end of long-term followup. Conclusions. the presence of cFABP ≥ 10 ng/ml in the blood of patients with acute myocardial infarction upon admission to hospital is associated with an increase in the probability of developing clinically evident heart failure during long-term follow-up by 4.27 times, and severe structural and functional remodeling of the left ventricle myocardium is 3.07 times more likely, which is due to the size of the infarction lesion and the subsequent development of myocardial fibrosis.
Aim: To assess the relationship between serum ceramides and the main cardiovascular (CVD) risk factors in coal mining industry workers. Material and methods: The single-center study included 209 Kuzbass mining industry workers aged 39.0 (34.0; 45.0) years. The median length of service in underground mining was 14.0 (10.0; 16.0) years. The traditional cardiovascular risk factors were evaluated and the ceramide content Cer (d18:1) with a fatty acid residue with a different length of the hydrocarbon chain was analyzed. Results: The results revealed high rates of smoking (73.2 %), arterial hypertension (AH) (63.3 %), alcohol consumption (54.1 %), dyslipidemia (64.6 %) and obesity (24.9 %) in coal industry workers. Hypercholesterolemia (60.3 %) and elevated levels of lowdensity lipoproteins (LDL-С) (34.5 %) were the most common variant of dyslipidemia. Moreover, we detected low levels of high-density lipoproteins (HDL-С) (23.9 %) and hypertriglyceridemia (23 %) in coal industry workers with the same frequency. Respondents over 40 years of age showed worse clinical profile compared to younger participants due to a higher number of cases with hypertension, higher systolic (SBP) and diastolic (DBP) blood pressure, plasma cholesterol (TC). In addition, older respondents presented with hyperglycemia 2 times more often and with hypercholesterolemia 1.4 times more often compared to younger respondents. Taking into account the age of participants, comparative analysis of ceramides did not reveal any statistically significant differences. The length of service in the industry was characterized by a higher age of the respondents, a higher frequency of hypertension, as well as higher values of DBP and concentration of TC. There were no differences in the frequency of dyslipidemia and its variants. The content of Cer (d18:1/21:0) increased with length of service, and the content of Cer(d18:1/24:0) had an inverse relationship and decreased with increasing length of service in underground mining. Thus, the levels of Cer(d18:1/12:0) and Cer(d18:1/22:0) were associated with a high risk of obesity, hypertension, dyslipidemia, hypercholesterolemia, low HDL, high LDL, and hypertriglyceridemia. The maximum number of ceramides studied was associated with the risk of developing high LDL levels. Conclusions. Findings showed high frequency of traditional CVD risk factors such as AH, smoking, alcohol consumption, dyslipidemia and obesity in coal industry workers. The concentration of the studied ceramides did not depend on the age of workers. Longer length of service in the coal industry was associated with an increase in plasma concentrations of ceramides such as Cer(d18:1/14:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer d18:1/21:0, and a decrease in Cer(d18:1/24:0). Cer (d18:1/24:0) was not associated with any of the parameters characterizing lipid metabolism disorders. Cer(d18:1/12:0) and Cer(d18:1/22:0) levels were associated with a high risk of obesity, hypertension, dyslipidemia, hypercholesterolemia, low HDL-С, high LDL-С and hypertriglyceridemia.
Aim of the study was to investigate the main epidemiological characteristics of hypertension (HTN), as well as factors associated with HTN, in the male rural population of 35–74 years old in Novosibirsk. Material and methods. On the basis of the Research Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, in 2021–2023, a one–stage population study of the urban and rural population of the Novosibirsk region was conducted according to the protocol of the study “Epidemiology of cardiovascular diseases and their risk factors in the Russian Federation. The third study”. A total of 1,800 people aged 35–74 years living in Novosibirsk and Novosibirsk region were examined. The analysis included 305 men living in rural areas. Hypertension was considered detected if the measurement of systolic blood pressure (SBP) exceeded 140 mm Hg and/or diastolic blood pressure (DBP) exceeded 90 mm Hg and/or there was a fact of taking antihypertensive therapy (AHT). Awareness was calculated as the proportion of people who had previously been informed by a doctor about the presence of HTN. The effectiveness of treatment is understood as the proportion of people who have achieved blood pressure targets while taking AHT. The control is the proportion of people who reached the target values among all those surveyed with HTN. Statistical processing of the obtained results was carried out using the SPSS software package (version 13.0). Associations were evaluated using multiple logistic regression analysis. The critical significance level of the null hypothesis (p) was assumed to be 0.05. Results. Median SBP and DBP among the rural male population are 148.0 [136.0; 164.3] and 94.0 [86.5; 103.5] (median [lower quartile; upper quartile]) mmHg respectively. The prevalence of hypertension among the examined men was 88.2 %. 83.3 % of men are aware of the presence of HTN. Among men with HTN, AHT is taken by 64.7 %. The effectiveness of treatment among the examined men is 17.2 %, 11.9 % of men control the disease. The multiple regression model revealed a significant positive association of treatment failure with hypertriglyceridemia and alcohol intake and a negative association with fasting plasma glucose levels: an increase in treatment failure with a decrease in glycemia levels. Conclusions. The prevalence of HTN among the male rural population of the Novosibirsk region is higher in comparison with the average Russian level. While awareness of the presence of hypertension is high, treatment coverage is significantly lower. It was also found that the vast majority of those examined are treated ineffectively and do not achieve disease control.
Purpose of the study: based on a longitudinal study, to assess the contribution of psychosocial factors to survival and the risk of developing cardiovascular diseases (CVD) among people 25–64 years old in Siberia (Novosibirsk, Tyumen, Tomsk). Materials and methods. On the basis of Research Institute of Therapy and Preventive Medicine – branch of the Federal State Budgetary Scientific Institution «Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences», Tyumen Cardiology Research Center – branch of the Federal State Budgetary Scientific Institution «Tomsk National Research Medical Center of the Russian Academy of Sciences», Research Institute of Cardiology – branch of the Federal State Budgetary Scientific Institution «Tomsk National Research Medical Center of the Russian Academy of Sciences» using the standard protocol for cardiac screening programs: «Study of the prevalence of coronary artery disease, risk factors for coronary artery disease in various regions of the country»; WHO «MONICA», which did not differ significantly, as well as the «MONICA-psychosocial» subprogram to identify psychosocial risk factors for cardiovascular diseases, cross-sectional studies were conducted on random representative samples of people 25-64 years old: Tomsk – 1981–1982 (n = 738 men); 1985–1986 (n = 1148 men); 1994–1995 (n = 637 men – postal survey and n = 450 men – cardiac screening); Tyumen – 1996 (795 men and 813 women); Novosibirsk – 1994 (657 men and 870 women). The cohort in Tyumen was observed for 12 years, in Tomsk for 19 years, and in Novosibirsk for 16 years. The following «end points» were recorded: death from ischemic heart disease (IHD), CVD, new-onset acute myocardial infarction (AMI) using the WHO program «Acute Myocardial Infarction Registry». Results. Among men and women 25-64 years old in Tyumen, a high 12-year relative risk of cardiovascular death was established in persons with a low level of education, in the professional group of heavy physical labor; in the male cohort – among single, widowed and divorced men. An assessment of the attributable risk of the social gradient in the male cohort showed the greatest contribution to cardiovascular death from the group of widows – 69.2 %, in the female cohort – from the group of people with a low level of education – 84.0 %. For men 25–64 years old in Tomsk, prognostically significant parameters of the social gradient of attributable risk are ranked as follows: 1) for mortality from IHD – working professions, lack of a permanent life partner, low level of education; 2) for mortality from CVD – working professions, average level of education, lack of a permanent life partner, low level of education. Among men and women aged 25–64 years in Novosibirsk, high levels of anxiety, depression and low levels of social support became prognostically significant risk factors for AMI for men and women; among men there is a high level of vital exhaustion. Conclusions. It was established that in the high: 12-year relative risk, 19-year attributable risk of cardiovascular death, the social gradient is prognostically significant. Anxiety, depression, vital exhaustion, social support play a leading role in predicting CVD in the Siberian region among the active working population.
The research is devoted to studying the prevalence of low-density lipoprotein (LDL) hypercholesterolemia in the population of 25–44 years old in Novosibirsk. Material and methods. The study was conducted on the basis of a population sample of Novosibirsk residents aged 25–44 years old, formed in the period 2013-2017 at RITPM – branch of the Institute of Cytology and Genetics SB RAS. This study included 1457 people (663 men, 794 women). The content of total cholesterol, triglycerides, high-density lipoprotein cholesterol and glucose was determined in the blood serum. Results. The prevalence of hypercholesterolemia in men and women in the age range from 25–44 years in Novosibirsk was 55.1 %, that is more than half of the total number of participants in the study. The prevalence of hypercholesterolemia among men exceeds that of women and the difference is statistically significant (p < 0.001). Conclusions. The identified differences between groups of men and women with different levels of LDL cholesterol indicate the importance of early diagnosis and treatment to reduce risks of cardiovascular diseases.
Aim. To study the clinical-biochemical parameters, APOE gene polymorphism in women with gallstone disease (GSD) with/without type 2 diabetes mellitus (T2DM). Materials and methods. In the open, single-stage, single-center, observational, cross-sectional, uncontrolled case-series study, 137 women with GSD were examined, including 71 patients with GSD and T2DM (Group 1), 66 patients – GSD without T2DM (Group 2) comparable age and BMI. The inspection included clinical examination, biochemical blood tests, including lipid profile, APOE gene polymorphism identification by PCR. Results. In group 1 met more often than in group 2 pain in the right hypochondrium (97.2 % vs. 86.4 %), in the left hypochondrium (42.3 % vs. 22.7 %), belching (88.7 % vs. 59.1 %), heartburn (78.9 % vs. 50.0 %), bitterness in the mouth (87.3 % vs. 57.6 %), stool disorders (83.1 % vs. 48.5 %, p < 0.05 in all cases). In group 1 were significantly higher than in group 2, TG (1.9 [1.5; 2.6] vs. 1.4 [1.0; 2.0] mmol/l), atherogenic coefficient (AC) (3.9 [3.1; 4.5] vs. 3.4 [2.5; 4.4] units), HDL-C – significantly lower (1.1 [1.0; 1.3] vs. 1.2 [1.1; 1.6] mmol/l). HypoHDL-C (69.0 % vs. 45.5 %) and hyperTG (66. 2% vs. 36.4 %) significantly more often observed in group 1. Systolic (140,0 [130,0; 150,0] and 130,0 [120,0; 130,0] mmHg, р < 0,001), diastolic blood pressure (SBP, DBP) (90,0 [80,0; 90,0] and 80,0 [80,0; 90,0] mmHg, р < 0,001), in group 1 higher than in group 2. APOE gene alleles frequency in group 1 and 2 is similar. There were no differences in the lipidogram in carriers of different alleles of the APOE gene in group 1. Conclusions. The presence of GSD and T2DM in group 1, both with cholecystolithiasis and after cholecystectomy, is associated with more conspicuous gastroenterological symptoms, lipid metabolism disorders, SBP, DBP increase, compared to group 2. There were no differences in the frequency of the alleles of the AРOE in groups 1 and 2, as well as in the lipidogram of carriers of different alleles of the AРOE in group 1.
Awareness of the population regarding the prevention of cardiovascular diseases remains insufficient. One of the methods of studying public health is a sociological survey of the population, the results of which allow us to form modern methods of preventive work with the population. Aim. To analyze the opinion of the population of Novosibirsk on adherence to a healthy lifestyle and the level of awareness of risk factors for the development of cardiovascular diseases. Material and methods. In 2024, a sociological survey of the population of Novosibirsk, 406 people, was conducted. The sample is sufficient in volume. Analytical, statistical, and sociological methods are used in the work. Extensive indicators were used in data processing and presentation, compared with the assessment of the statistical significance of differences according to the Student’s t-criterion. Results. The awareness of the population in matters of a healthy lifestyle, commitment to a healthy lifestyle and the level of awareness of the population about risk factors for the development of cardiovascular diseases are determined. Respondents of all age groups are well informed about the influence of the main risk factors for the development of cardiovascular diseases, it is determined that each age group has its own set of risk factors for the development of cardiovascular diseases. Conclusions. In general, the data obtained make it possible to identify additional resources to increase public awareness of development risk factors, including on the basis of information technology.
A CLINICAL CASE
A clinical case of surgical treatment of an extracranial internal carotid artery aneurysm of type II according to N. Attigah of a patient with multiple aortic aneurysms 14 years after a previous resection of an infrarenal aortic aneurysm with aorto-femoral bifurcation replacement in 2004 is presented. In 2005, due to infection of the right branch of the prosthesis, a right prosthetic-femoral bypass was performed. Subsequently, examination revealed an aneurysm of the arch and thoracoabdominal aorta of Crauford type III. This case shows the need for constant follow-up of patients after open surgical treatment of aortic aneurysms.
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