Search

Currently, veterinarians pay much attention to the diagnostic examination of animals, including animals kept on fur farms. Blood is the main material used for such examinations. Changes in its composition allows veterinary practitioners to identify disorders in various systems and organs of animals, as well as to assess metabolism in animals. Results of biochemical tests of serum samples from platinum fox males and females of different age groups and comparative assessment thereof are presented. The levels of aspartate aminotransferase (U/L), alanine aminotransferase (U/L), alkaline phosphatase (U/L), total protein (g/L), albumin (g/L), urea (mmol/L), creatinine (μmol/L), α-amylase (U/L), cholesterol (μmol/L) were determined. Aspartate aminotransferase levels in females at the age of 6 months were lower by 69% than that ones in males. Increase in aspartate aminotransferase by the age of 6 months helps animals to accumulate body weight before winter. Sexual differences in the alkaline phosphatase levels were detected in 1.5-month-old kits: alkaline phosphatase levels were higher by 21.05% in males than in females. By the age of 6 months, the alkaline phosphatase levels decreased in both males and females. The decline in alkaline phosphatase level with the age is associated with participation of this enzyme in the development of animal skeleton during ontogenesis. From the age of 4 months, the growth and development of the skeleton slows down, and by the age of 6 months the animals gain the size and body weight of adult animals. Urea and creatinine levels in foxes of both sexes increased during their growth, but remained within the reference limits. Changes in urea levels in blood can be caused by feeding excessively high-protein or excessively low-protein diets. The total protein content in sera from 4 month-old males and females decreased by 32.51 and 43.24%, respectively, compared with that one in sera from animals at the age of 1.5 months, and increased at the age of 6 months up to the level observed at the age of 4 months. According to the literature, rather rapid stabilization of protein metabolism is a biological feature of many mammals born in spring, their growth rate is accelerated and, in general, the maturity phase is shortened.

In the present study, the effects of temperature changes during summer and winter seasons on haematological parameters, total cholesterol, and cortisol level in male and female Syrian Awassi sheep were studied. Blood samples were collected weekly from ten animals (five rams and five ewes) during August and January months (2022-2023), and these samples were analyzed by a Veterinary Hematology Analyzer to determine the haematological parameters, and by enzyme-linked immunosorbent assay technique (ELISA) to determine the level of cortisol and total cholesterol. The results showed that there were significant differences in white blood cells (WBC), monocytes (MON) and granulocytes (GRA), as well as in haemoglobin (HGB) between August and January for both females and males. No significant difference was recorded between the two months for both sexes regarding platelet count (PLT) and mean platelet volume (MPV). There were significant differences (P < 0.001) between the months of August and January in females for the level of cortisol and cholesterol, while no significant difference (P > 0.05) was recorded for males between these two months. It was concluded that there were significant differences in the values ​​of some blood components between summer and winter for males and females Awassi sheep, but the differences in the level of total cholesterol and cortisol were clearer in the females than in males between summer and winter. In general, this study showed the ability of the Syrian Awassi sheep to adapt higher temperature degrees than the lower ones in semi-arid area where Syrian Awassi flocks are raised.

The review presents contradictory results from numerous clinical and epidemiological studies, giving reason to doubt the indisputability of ideas about the primary role of low-density lipoprotein (LP) cholesterol in atherogenesis and the efficacy of lipid-lowering therapy. The latter clearly demonstrates the absence of the expected clinical effect in reducing cholesterol levels after surgical correction of lipid metabolism (ileal bypass surgery) or a very modest effect when using drugs devoid of pleiotropic properties. This circumstance finds an explanation in the fact that, according to modern concepts, only modified LP are the molecular substrate of the pathophysiological process at all stages of atherosclerosis development. Native (intact) LP, the concentration of which in the blood does not correlate with the level of modified forms, are not included in the pathogenesis of atherosclerosis. Consequently, the presence of native LP in the blood does not give a true picture of the activity of the atherosclerotic process. Based on the above, in the treatment of atherosclerosis, it should be considered justified not so much to further improve methods of lipid-lowering effects on the body, which do not have a sufficiently reliable evidence base of clinical effect, but to search for means that prevent the generation of atherogenic, modified LP. In this regard, taking into account the important role of systemic inflammation in the pathogenesis of atherosclerosis, the synthesis and clinical use of safe anti-inflammatory drugs, as well as the development and implementation of methods aimed at eliminating the causes of systemic inflammation, should be considered promising.

Cardiovascular disease remains one of the leading causes of mortality worldwide, with elevated LDL cholesterol being a critical risk factor. Statins have long been the cornerstone of lipid-lowering therapy, but many patients fail to reach target LDL cholesterol levels due to statin intolerance or insufficient response, even when combined with ezetimibe. Recently, the lipid-lowering drug class has been expanded with the introduction of bempedoic acid, a novel agent that inhibits ATP-citrate lyase. Recent studies have demonstrated the efficacy and safety of bempedoic acid in reducing LDL cholesterol levels in patients with hypercholesterolemia, paving the way for its inclusion in clinical guidelines. This article provides a comprehensive overview of the latest evidence regarding bempedoic acid and its emerging role in lipid management. Despite the widespread use of statins, many patients fail to achieve target LDL-C levels due to statin intolerance or insufficient response. This comprehensive review explores the emerging role of bempedoic acid, a novel lipid-lowering agent that inhibits ATP-citrate lyase, in the management of dyslipidemia and cardiovascular risk reduction. Bempedoic acid, approved by the FDA in 2020, offers a unique mechanism of action that complements existing therapies. As a prodrug activated specifically in the liver, it avoids muscle-related side effects commonly associated with statins. Clinical trials have demonstrated its efficacy in reducing LDL-C levels, particularly in patients with statin intolerance or those requiring additional LDL-C lowering beyond maximally tolerated statin therapy. The review synthesizes data from multiple phase 3 clinical trials, including CLEAR Wisdom and CLEAR Outcomes, which have shown significant LDL-C reductions with bempedoic acid monotherapy and in combination with other lipid-lowering agents. Notably, bempedoic acid not only lowers LDL-C but also reduces high-sensitivity C-reactive protein (hs-CRP) levels, suggesting potential anti-inflammatory effects. Safety profiles from these trials indicate that bempedoic acid is generally well-tolerated, with minimal muscle-related adverse events. However, slight increases in serum creatinine and uric acid levels have been observed, warranting monitoring in certain patient populations. Recent updates to clinical guidelines, including the 2024 European Society of Cardiology guidelines on coronary heart disease, now recommend bempedoic acid for specific patient groups. These include statin-intolerant patients not achieving LDL-C goals on ezetimibe alone, and those not reaching targets on maximum tolerated statin doses combined with ezetimibe. This review concludes that bempedoic acid represents a significant advancement in lipid-lowering therapy, offering a valuable option for patients with hypercholesterolemia, particularly those with statin intolerance or requiring additional LDL-C reduction. As research continues, bempedoic acid's role in reducing cardiovascular events and its long-term safety profile will be further elucidated, potentially reshaping the landscape of dyslipidemia management and cardiovascular risk reduction.

Introduction. Lipid metabolism disorders, caused by both excessive physical and psycho-emotional stress, and physical hypoxia, are important problems in the prevention and treatment of a number of diseases.The objective was to study the effect of 1,2,4-trioxolanes and betulin in fish oil on lipid and energy metabolism in an experiment on rats under hypoxia and immobilization stress (IS).Methods and materials. The studies were carried out using 75 male Wistar rats (intact and experimental animals) on a model of hypoxia and immobilization stress for 10 days. The treatment was carried out with the composition of betulin (0.1 %), 1,2,4-trioxolanes (10 %) in fish oil.Results. Under stress, regardless the type of stress, in groups without treatment, there was a significant disturbance in lipid metabolism, which was reflected in the following indicators: total cholesterol increases by 5–8 %, TG increase by 5 times, HDL increase by 10 %, VLDL and LDL increase by ~ 6 times. It was revealed that the composition of fish oil, botulin and 1,2,4-trioxolanes, previously obtained by ozonation of lipids, had a normalizing effect on the indexes of lipid and energy metabolism under hypoxia and IS in rats.Conclusions. 1,2,4-trioxolanes with betulin in fish oil may be useful for population groups with physical inactivity (students, office workers, elderly people, disabled people), as well as for athletes with excessive physical activity.

This work presents ultraviolet (UV) spectra of various concentrations of polyene antibiotics. The spectra of Levorin and Amphotericin B differ in three main absorption maxima. The maximum absorption spectra of antibiotics vary in the range of 370–430 nm. UV absorption spectra reflect the characteristic spectrum of polyenes belonging to this class. Amphotericin B and Levorin in combination with cholesterol lower the maximum of the UV absorption spectra. Analysis of the obtained results shows that cholesterol molecules, combining with double-bond systems of Amphotericin B and Levorin, gradually reduce the maximum absorption of UV spectra, which creates opportunities for their more active use in various fields of biomedicine.

Dyslipidemia – increased blood levels of cholesterol, triglycerides and atherogenic lipoproteins and/or decreased levels of anti-atherogenic high-density lipoproteins. Dyslipidemia is considered one of the main biological risk factors for chronic non-communicable diseases, along with overweight and obesity, arterial hypertension and hyperglycemia. The initial stage of correction of dyslipidemia begins with dietary recommendations, in which omega-3 polyunsaturated fatty acids occupy an important place. The effects of the main substances included in the combined nutraceutical Cholesterol Control are considered: omega-3 polyunsaturated fatty acids, including eicosapentaenoic and docosahexaenoic acids, red yeast rice, coenzyme Q10, which allows us to consider it the nutraceutical of choice for low and moderate risk individuals with moderately elevated cholesterol and triglycerides, no indications for taking statins or the presence of contraindications to taking them. Periodontitis is the sixth most common disease in the world (second among dental pathologies after caries) and the leading cause of tooth loss in adults. At the beginning of the 21st century, the concept of “periodontal medicine” was formed, within the framework of which the bidirectional connection of periodontal pathology with systemic diseases of the body is considered. We searched the PubMed and Scopus information databases for articles published before 02/15/2024 that examined the relationship between dyslipidemia and periodontal pathology. The results obtained indicate the presence of a bidirectional relationship between dyslipidemia and periodontal pathology. The analysis showed the positive effect of omega-3 polyunsaturated fatty acids and coenzyme Q10 on the inflammatory process in periodontal tissue and allows us to consider the nutraceutical Cholesterol Control as an adjuvant therapy in comorbid patients with dyslipidemia and periodontal pathology, as well as for the prevention of lipid disorders in patients with periodontal diseases.

Introduction. In this study, we aimed to identify the features of the dynamics of cardiovascular diseases (CVD) and risk factors for its development in individuals who have worked under the influence of noise for a long time. Patients and Methods. 56 archival case histories of patients with occupational sensorineural hearing loss and 47 outpatient records of patients who worked in relative silence were studied. CVD and cardiovascular risk factors were analyzed in dynamics. Results. The groups were comparable in age, body mass index, prevalence of smoking, obesity and burdened heredity. In patients with occupational sensorineural hearing loss, total cholesterol exceeded the upper limit of normal and the level in the comparison group, and was, respectively, 5.6 ± 1.2 mmol/l and 5.0 ± 0.9 mmol/l (p = 0.046) at the first visit and 5.6 ± 1.1 mmol/l and 5.2 ± 1.1 mmol/l at the last visit (p = 0.037). Hypertension was the leader in the structure of CVD in both groups. In individuals with occupational sensorineural hearing loss, the total number of cases of atherosclerotic cardiovascular diseases was significantly higher, both at the first (5 and 0 cases, respectively, p = 0.04) and at the last visit (14 and 3 cases, respectively, p = 0.01). Conclusion. Individuals who have worked in noise for a long time have an increased cardiovascular risk by the time occupational hearing loss is established. Abnormalities of lipid metabolism presumably represent a main contribution to the formation of this risk. At the same time, atherosclerotic cardiovascular diseases are more often detected among individuals who worked in noise than among those who worked in relative silence.

Scientific relevance. The main cause of cardiovascular pathologies is atherosclerosis, which is secondary to lipid metabolism disorders, in particular, the accumulation of low-density lipoprotein (LDL) cholesterol. Dyslipidaemia treatment with the largest evidence base predominantly includes statins in combination therapy, but their use is limited by into lerance in some patients. Alternatively, the treatment may include proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.Aim. The study aimed to analyse the applicability of PCSK9 inhibitors in patients with statin intolerance.Discussion. According to the literature analysis, the most common presentation of statin intolerance is statin-associated muscle symptoms. The pathogenesis of statin-associated adverse events is mainly mediated by HMGCoA reductase inhibition, treatment effects on cellular and subcellular processes and skeletal muscles, and patients’ genetic makeup. The mechanism of action of PCSK9 inhibitors is entirely different and involves binding and inactivation of the PCSK9 protein, which lowers blood LDL cholesterol levels. PCSK9 inhibitors have been associated with some adverse drug reactions, most notably immunogenicity; however, PCSK9 inhibitors effectively reduce LDL levels even if patients develop antibodies.Conclusions. Therefore, PCSK9 inhibitors are a safe, well-tolerated, and effec tive therapeutic strategy for hyperlipidaemia in patients with statin intolerance.

Scientific relevance. Cardiovascular diseases (CVD) are the leading cause of death worldwide. Dyslipidemia, as the pathophysiological basis of atherosclerosis, is the most important cause of CVD. Among the factors that modify this pathology, the World Health Organisation lists statins, which effectively reduce the cholesterol level. However, statin treatment compliance is not sufficient to achieve population-based lipid targets. This is a powerful stimulus for the creation of fundamentally new groups of lipid-lowering agents, in particular, antagonists of proprotein convertase subtilisin/kexin type 9 (PCSK9).Aim. The study aimed to review innovative approaches to developing a new generation of lipid-lowering agents, PCSK9 antagonists, and to evaluate the effectiveness, safety, and clinical potential of these medicines.Discussion. PCSK9 antagonists significantly increase the effectiveness of lipid-lowering therapy when combined with statins and are an effective monotherapy in patients with contraindications for statins. PCSK9 monoclonal antibodies, as well as inclisiran, have a favourable risk–benefit ratio. However, the high cost of commercially available PCSK9 antagonists limits their clinical use. A number of promising directions exist for developing new PCSK9 antagonists that have fundamentally different mechanisms of action, such as adnectins; genome editing with CRISPR/Cas9; combining small molecules with low molecular weight PCSK9 inhibitors; PCSK9 vaccines; and antisense oligonucleotides. Medicinal products from these groups are currently at various stages of preclinical and clinical development.Conclusions. Therefore, new lipid-lowering agents can be developed by synthesising high and low molecular weight PCSK9 ligands and by altering the genetic mechanisms of PCSK9 synthesis. The innovative medicines considered in this review are highly effective, and most have shown no signs of toxicity at the pre-authorisation stage.

Obesity contributes to the development of severe concomitant diseases and substantially degrades the quality of life. This pathological condition is caused by multiple risk factors including hazardous workplace exposures and genetic predisposition. The ApoE gene participates in regulation of lipid metabolism. Its most significant polymorphisms are rs429358 and rs7412 with the resulting е2, е3 and е4 alleles. This study did not consider effects of electromagnetic fields generated by office electrical equipment or the lifestyle of the subjects. The sample included people with a large age difference due to the rarity of the apolipoprotein е2 and е4 alleles. The sample was not standardized by age and years of work experience. The aim of this study was to investigate associations between the ApoE gene polymorphisms and body mass index in workers employed at a metallurgic plant. We examined 328 male office workers and workers of a converter workshop. The body mass index (BMI) was calculated based on the results of instrumental measurements of weight and height using the conventional formula. DNA was isolated from peripheral blood using the LumiPure DNA gel extraction kit, and polymorphisms were determined using amplification by Calero et al with modifications and horizontal agarose gel electrophoresis. The data were analyzed using the Kruskal – Wallis test. Statistically significant differences were established in the blue-collar workers. The highest mean BMI value was established in the e2 allele carriers. We found that people with the e2 allele in their genotype were more prone to obesity. We also assume a potential association between the unsafe work environment and a more pronounced manifestation of the phenotype. These findings can be used for identifying individuals at risk and taking timely preventive measures.

Introduction. One of the most progressive directions of the modern stage of development of biology is the deepening of knowledge about the mechanisms of regulation of metabolic processes, in particular about signal molecules that transmit information to the cell through ion channels and nuclear receptors associated with G-protein or with enzymatic activity. The nuclear Farnesoid X receptor (FXR) is mainly expressed in the liver and intestines, it regulates key genes that provide the processes of synthesis, transport and reabsorption of bile acids, and is also involved in the metabolism of lipids and carbohydrates.Aim. To evaluate the effect of a farnesoid X receptor agonist on postprandial lipemia in rats fed a supraphysiological fat diet.Materials and methods. An experimental, prospective, controlled, unblinded, randomized study was conducted to study the effect of a farnesoid X receptor agonist (obeticholic acid) on postprandial lipemia in rats receiving a diet containing a supraphysiological dose of fats.Results and discussion. It has been shown that when assessing postprandial lipemia, an oral test for tolerance to supraphysiological doses of fat with the determination of the initial lipid profile parameters and 4 hours after exercise has a sufficiently high information content. It was found that in animals that received a diet containing an increased amount of fat for 28 days, there was an imbalance in lipid metabolism with activation of their absorption in the intestine, but a "slow" reaction of the mechanisms of intermediate lipid metabolism, which was accompanied by the accumulation of triglycerides and cholesterol in the blood of hungry rats, chylomicrons and LDL. At 4 hours post-feeding, these animals showed abnormal increases in triglycerides and cholesterol.Conclusion. The use of obeticholic acid harmonizes lipid metabolism against the background of alimentary fat load, due to the activation of farnesoid X-receptors of the intestine and liver, which is manifested by a simultaneous increase in the intensity of lipid absorption processes and their intermediate metabolism. As a result, the risk of hyperchylomicronemia, hypercholesterolemia and hypertriglyceridemia is eliminated, the likelihood of developing secondary hyperlipedemia, insulin tolerance and functional overload (or pathology) of the liver is reduced.

Introduction. The Laboratory of Drug Formulation Development at the N. N. National Medical Research Center of Oncology developed a liposomal dosage form of FS tetra-3-phenylthio-pthalocyanine hydroxyluminide (TPHA) for which a simple, accurate and easily reproducible method of quantitative determination of the main active substance and excipients in the drug product was needed. High-performance thin-layer chromatography (HPTLC) was chosen as such a technique.Aim. The aim of this work was to develop chromatographic methods for the quantitative determination of excipients in a liposomal dosage form of a tetra-3-phenylthiophthalocyanine hydroxyaluminium (TPHA).Materials and methods. Determination of substances was carried out by the method of high-performance thin-layer chromatography (HPTLC) followed by TLC-densitometry. Substance TPHA 98 % (Federal State Unitary Enterprise "SSC "NIOPIK", Russia), placebo lyophilized liposomal form without TFHA in the composition (FSBI "National Medical Research Center of Oncology. N. N. Blokhin" of the Ministry of Health of Russia), egg phosphatidylcholine (96 %, CAS № 97281-44-2, EPC Lipoid, Germany), cholesterol (≥99 %, CAS № C8667, Sigma-Aldrich, Japan), sucrose analytical grade (CHIMMED, Russia) and various organic solvents.Results and discussion. The selected mobile phase for HPTLC analysis: isopropanol: ammonia 25 % aqueous 80 : 20, separation time was 20–25 min (l = 75mm), t = 20 °С. To visualize the spots of sucrose, phosphatidylcholine, and cholesterol, a 5 % solution of phosphomolybdic acid was chosen. The stability of the standard samples was confirmed on a series of prevalidation studies. Validation of the methodology was carried out.Conclusion. For quantitative determination of sucrose, phosphatidylcholine and cholesterol in a new liposomal dosage form, the method of HPTLC with TLC-densitometry was chosen, which allows identifying all three components in the dosage form simultaneously. The method was validated.

Introduction. Adropin is a new secretory hormone that takes part in the regulation of energy homeostasis. Hormone is known to have positive effects on endothelial cell proliferation and prevention of atherosclerosis, and low adropin level may be a risk factor and potential predictor of atherosclerosis. Arterial hypertension (AH), which remains one of the most common somatic pathologies among middle-aged and older people, plays an important role in predicting cardiovascular morbidity and mortality. A number of medications that are used as antihypertensive therapy contribute to an increase in the content of adropin. At the same time there are not enough studies on the effect of statins on the content of adropin. Aim of the study.To investigate the effects of statins on adropin level in patients with AH. Material and methods. 70 patients with hypertension aged 62,1 ± 9,9 years were examined. They were divided into 2 groups: 1 group – patients with AH, overweight and obesity who did not take statins (n=40); group 2 – persons with AH, overweight and obesity who took statins (n=30). All individuals underwent determination of basic indicators of biochemical blood analysis, lipid profile (total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglycerides (TG), atherogenicity ratio). The level of adropin was determined by enzyme immunoassay (Finetest Elisa Kit) in blood serum. Results. Systolic blood pressure (BP) was significantly higher in group 1 individuals (p0.05). Among patients who took statins, a significantly lower level of TC, LDL, atherogenicity ratio (p

The aim of the work is to study pharmacological substances that play a role of eNOS expression regulators in the modification of lead intoxication effects in the experiment.Materials and methods. In the experiment, linear male rats of the same age were used: intact and with lead intoxication (120 heads). The study design was the following: group 1 – control; group 2 – intoxication with a lead acetate solution; group 3 – intact + L-nitroarginine methyl ester; group 4 – lead acetate + L-nitroarginine methyl ester; group 5 – intact + L-arginine; group 6 – lead acetate + L-arginine. The research carried out the study state of the redox reactions, the content of nitric oxide (NOx) stable metabolites, a lipid profile, the level of NO-synthase (eNOS) expression in the vascular endothelium, the main processes of urination and the activity of Na+/K+-ATPase in the renal tissue layers, as well as in the liver. The results were subjected to statistical processing.Results. Saturnism caused the oxidative stress development, a decrease in the NOx content in blood plasma, a violation of the L-arginine for eNOS bioavailability, and an endothelial dysfunction. Indicators of the impaired renal function were a decrease in the glomerular filtration rate (GFR), the tubular reabsorption of water, sodium, and the Na+/K+-ATPase activity. The damage to hepatocytes was evidenced by changes in the activity of organ-specific enzymes in the blood and Na+/K+-ATPase. L-arginine exhibited antioxidant properties, increased the NOx content and the level of eNOS expression. The eNOS L-nitroarginine methyl ester inhibitor showed the effects opposite to L-arginine.Conclusion. Biochemical markers of damage to kidney and liver cells during saturnism are indicators of the oxidative stress, NOx deficiency and hemodynamic disturbances in them. These mechanisms involved the following pharmacological substances: an eNOS inhibitor, L-nitroarginine methyl ester, which caused a decrease in the expression level of the enzyme, and an eNOS inducer, L-arginine, which increased this indicator severity. The lead toxicity mechanisms have been implicated in the impaired cholesterol metabolism, contributing to the L-arginine reduced availability for eNOS and the NOx production. Therefore, the use of L-arginine can be recommended as a regulator of the oxidative stress and an NO-producing endothelial function in other pathologies.

Objectives. To determine the effect of end-stage renal failure on the biochemical composition of blood lipoprotein complexes. Material and methods. The work is carried out within the frames of the State Research Program «Translational Medicine, 2020 - 2025», subprogram 4.2 «Fundamental Aspects of Medical Science» on task 3.37, State Registration Number 20220305. The study group of patients was composed of 15 men (36-60 years old) and 16 women (36-55 years old) with the end-stage chronic kidney disease, the control group consisted of 15 healthy men and women of the same age. Lipoprotein complexes (LPC) were isolated by sequential ultracentrifugation on the preparative ultracentrifuge, the amount of protein in native LPC was determined by the Lowry method, cholesterol and triacylglycerides – by a biochemical method, proprotein convertase subtilisin kexin 9 (PCSK9) – by enzyme immunoassay in blood serum. Results. There are no gender differences characteristic of healthy subjects in the individuals of the study group. In patients with chronic renal failure (CRF), the level of VLDL TG is higher than that in the control group, and cholesterol and VLDL protein are increased compared to healthy women. The amount of LDL TG in the study group is higher compared to the control group, and the amount of LDL protein is increased in comparison with women in the control group. Conclusion. CRF possesses a proatherogenic effect and eliminates gender differences characteristic of healthy individuals, and it also has a stronger effect on women, increasing the content of total VLDL cholesterol and VLDL and LDL protein. CRF does not affect the amount of PCSK9.

Neurofibromatosis type 1 is caused by a germline mutation in the NF1 gene encoding the tumor suppressor neurofibromin. Deficiency of this protein causes hyperactivation of Ras proto-oncogenes. This leads to the development of tumors. Ras proteins undergo prenylation, which is inhibited by inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Therefore, statins can be proposed as anticancer drugs in the complex treatment of neurofibromatosis type 1. Clinical studies have proven the effectiveness of statins in the treatment of sporadic malignant neoplasms, in the pathogenesis of which mutations in the NF1 gene play an important role. Various pathways of the influence of these drugs on the development of tumors are described, including the activation of autophagy, ferroptosis, suppression of proliferation, stimulation of antitumor immunity, and effects on the microenvironment of neoplasms. Data on the effect of statins on the development and progression of neurofibromas in patients with neurofibromatosis type 1 are not presented in the scientific literature. However, it was found that statins enhance the effect of anticancer drugs, the use of which in monotherapy against malignant neoplasms associated with neurofibromatosis is ineffective. In this regard, despite the inefficiency of statins in cognitive disorders in patients with neurofibromatosis type 1, the introduction of these drugs into clinical practice in combination with other drugs could provide a pleiotropic effect, affect various links in the pathogenesis of the disease.

Introduction. A disorder of lipid metabolism is very often observed in patients with chronic viral hepatitis B and C, which can lead to the progressive damage of the liver parenchyma with future severe evolution of chronic liver pathology. The disturbance of cholesterol metabolism under the action of viral, metabolic and other factors leads to the pathological accumulation of free cholesterol in hepatocytes, and the development of nonalcoholic fatty liver disease with steatosis or steatohepatitis and liver fibrosis. The aim of the study was to study certain indices of lipid metabolism in patients with chronic viral hepatitis HBV, HCV and mixed viral etiology HBV+HCV in reference to cytolysis syndrome. Material and methods. In the study participated 138 patients with chronic viral hepatitis of chronic viral etiology HBV, HCV and HBV+HCV. Patients were divided into 3 groups according to the etiology of viral etiology: group I consisted of patients (n = 58) with chronic viral hepatitis of HBV etiology. Group II presented patients (n = 69) with chronic viral hepatitis, of HCV etiology. Group III consisted of patients with chronic viral hepatitis mixed form: HBV+HCV (n = 11). The comparison group consisted of 30 practically healthy people. Results. The study revealed a significant increase in cytolysis syndrome indicator enzymes, alanine aminotransferase and aspartate aminotransferase, with a significant increase depending on the viral etiology, being high in group II (p

Statins have long occupied a central place in cardiovascular medicine, being an integral component of the prevention and treatment of atherosclerotic cardiovascular diseases (coronary heart disease and its main clinical forms, angina pectoris and myocardial infarction; transient ischemic attacks, ischemic strokes, etc.). By blocking a key enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase), statins normalize the parameters of the lipid spectrum, primarily, the serum levels of atherogenic low-density lipoprotein cholesterol. However, in addition to the beneficial effects of statins, side effects are also characteristic, which are a significant problem in modern clinical practice due to the fact that they can cause dangerous disorders, forcing physicians to reduce dosages or completely cancel these drugs. Understanding the side effects and the mechanisms underlying their formation is important for improving the measures for the early detection, prevention and treatment of those disorders. This article discusses such side effects of statins as myotoxicity, hepatotoxicity, nephrotoxicity. The pathogenetic mechanisms underlying these toxic effects of statins are discussed. A particular attention is paid to the effect of statins on the oxidative stress, the mechanisms of oxidative damage to cellular macromolecules (lipids, proteins and DNA) and their potential role in the development of myotoxicity, hepatotoxicity and nephrotoxicity.

Antitumor drug treatment of hemoblastoses always takes into account the patient comorbidity. Due to the frequent cardiovascular pathology and atherosclerosis, patients have to take statins along with antitumor treatment. Experimental studies have shown that statins inhibit the cholesterol synthesis (necessary for the vital activity of malignant cells), isoprenylation of the RAS and RHO oncogenes, and the proliferation of leukemic cells. In addition, the potentiation of antitumor drugs effect by statins, sensitization of leukemia and lymphomas cells to their effects were noted. when conducting a meta-analysis, it was found that mortality among patients with hematological malignancies taking statins is lower compared with the group of patients not receiving statins. This fact is probably explained not only by the improvement in cholesterol metabolism, but also by indirect antitumor effects of this group of drugs.

Aerobic exercise training is recommended to prevent and control obesity. The present study aimed to evaluate the effectiveness of a twelve-week step aerobics or floor aerobics exercise program in improving the physical and psychophysiological health of obese men. Sixty male adults of mean age 18.92 (SD 1.54 years) and Body Mass Index (BMI) ≥ 30 kg/m2 were randomly allocated into three equal (n = 20) groups: Step Aerobics Exercise Training (SAET), Floor Aerobic Exercise Training (FAET), and a control group (which did not perform any exercise). The SAET and FAET training protocols were performed three days per week for 12 weeks. Health-related physical fitness, biochemical, physiological, and psychological variables were used as outcome measures and measured at baseline and at 12 weeks. There were significant differences in terms of physical and psychophysiological health parameters in participants who underwent SAET and FAET training compared with the control group (p < 0.05). SAET and FAET proved to be helpful in managing the physical and psychological health of obese adults. Schools and colleges should administer aerobic exercise sessions to adults for better health perspectives.

The aim of the study is to determine antioxidant, anti-inflammatory and hypolipidemic activities of the extracts from Cosmos bipinnatus Cav. three varieties, obtained by the extraction with 70% ethyl alcohol.Materials and methods. The antioxidant effect was studied in vitro using a model of iron-induced lipid peroxidation in the lecithin liposome system. The study of the anti-inflammatory activity was carried out on 30 male rats of the “Wistar” line. Diclofenac was used as a reference drug (p. o., the dose of 13 mg/kg in terms of the weight of an adult). The substances were administered to animals in the form of an aqueous suspension stabilized with Tween-80. To simulate the inflammatory process, a model of “cotton granuloma” was created. A hypolipidemic activity of the extracts was studied on 36 white male rats of the “Wistar” line. To study the hypolipidemic activity of the studied extracts, a tween model was used to create a hyperlipidemic state in rats, the concentrations of total cholesterol and triglycerides was determined in the serum of the experimental animals.Results. The conducted model experiments made it possible to conclude that the alcohol extracts obtained from the dried inflorescences of the “Dazzler”, “Rosea” and “Purity” varieties of Cosmos bipinnatus Cav. have antioxidant, anti-inflammatory and hypolipidemic kinds of activities. It has been established that the extracts from the “Dazzler” and “Rosea” varieties (Cosmos bipinnatus Cav.) contribute to a better reduction in the accumulation of peroxide compounds, compared to the extract obtained from the “Purity” variety. The data analysis on the anti-inflammatory activity shows that all the studied objects significantly (p = 0.05) reduce the stage of exudation compared with the control group animals by 50% (the «Purity» variety), by 52% (the «Rosea» variety) and by 40% (the “Dazzler” variety).An experiment on the study of a hypolipidemic activity in the control group of the animals revealed a significant, in relation to the values of the intact group, increase in the cholesterol level of the blood serum by 78%, and in the level of triglycerides (TGCs) – by 64%.The administration of the extracts obtained from Cosmos bipinnatus Cav. “Purity”, “Rosea”, “Dazzler” varieties to the animals, led to a decrease in cholesterol in blood serum by 44%, 47%, 50%, and triglycerides by 52%, 52% and 57%, respectively. Both indicators reached the normal level and did not differ significantly from the values in healthy (intact) animals.Conclusion. According to the conducted studies, it can be concluded that alcohol extracts obtained from Cоsmos bipinnatus Cav., have pronounced antioxidant, anti-inflammatory and hypolipidemic kinds of effect.

The aim of the study was to investigate circulating miRNAs-27a, -221 levels and their correlations with lipid indices in patients with ischemic heart disease (IHD) and type 2 diabetes mellitus. Materials and methods. The study included 58 patients with stable IHD and type 2 diabetes mellitus, 22 IHD patients without diabetes and 19 healthy controls. MicroRNAs-27a-3р and 221-3р were determined in blood plasma by real time polymerase chain reaction. U6 small nuclear RNA was used for normalization. Results. The lowest levels of circulating miRNAs-27a and -221 were in IHD patients with diabetes. The decrease in the levels of both microRNAs in patients with diabetes was significant not only in comparison with the control group (P = 0.024, P = 0.006), but also with patients without diabetes (P = 0.011, P = 0.001). In IHD patients without diabetes, microRNAs-27a and -221 levels did not change significantly. In IHD patients with diabetes, microRNA-221 showed a significant positive correlation with high-density lipoprotein cholesterol (HDL-C) (R = 0.382, P = 0.003). MicroRNA-27a was correlated negatively with triglycerides (TG) (R = -0.284, P = 0.051) and positively – with HDL-C (R = 0.257, P = 0.078) at a borderline significance level. The lower level of microRNA-27a (the 1st tertile) was associated with significantly increased TG level in comparison with the 3rd tertile (P = 0.004), and significantly decreased HDL-C level in comparison with the 2nd (P = 0.001) and the 3rd (P = 0.023) tertiles. Patients with lower microRNA-221 level (the 1st tertile) had significantly reduced HDL-C level in comparison with the 3rd tertile(P = 0.007). Conclusions. The results have demonstrated the significant decrease in circulating microRNAs-27a and -221 levels in IHD patients with type 2 diabetes mellitus and no change in both microRNAs in patients without diabetes. In IHD patients with diabetes, the lower expression of microRNA-27a was associated with the significant elevation of TG and the significant decrease in HDL-C. The lower microRNA-221 level was associated only with the significant decrease in HDL-C.

Aim. Study the effect of a study video, which was created by researchers and devoted to the atherosclerosis development and the effect of statin therapy on atherosclerotic plaque, on adherence to long-term therapy in patients with high or very high risk of cardiovascular complications.Material and methods. 120 patients admitted to hospital with cardiovascular diseases were included in the study. Patients were randomized into 2 groups: in the main group (n=60), the information video edited by the researchers was shown to patients on the eve of discharge, in addition to a printed brochure on lifestyle and diet modification, and in the control group (n=60), patients were given only a standard brochure. The motivating video shows the damage to the cardiovascular system by the atherosclerotic process and the beneficial effect on the body of constant intake of statins. After 1 and 3 months after discharge from the hospital, telephone calls were made, after which the patients had to visit the center for an objective examination by a researcher and control of laboratory parameters. After 1 month, 110 patients visited the center, after 3 months, 98 respondents visited the center.Results. The group with the information video demonstration noted more frequent adherence to medical recommendations compared to the control: after 1 month, 52 (96%) patients continued treatment versus 48 (86%) patients, 3 months after discharge 48 (96%) patients continued treatment versus 38 (79%) patients (p

Background. Male infertility refers to multifactorial diseases that have been studied quite deeply and the role of arterial hypertension and lipid metabolism in the mechanism of its development has not been studied at all. The purpose of the study is to evaluate the functional features of seminal fluid spermatozoa and the lipid spectrum of blood serum to identify the pathogenetic mechanisms underlying male infertility in hypertension. Materials and methods. The data of the initial examination of the patient and the signing of informed consent for the study are reflected in the outpatient card. Criteria for inclusion in the study: the absence of pregnancy in the spouses during the year of married life together, obtaining seminal fluid in the sterility room and timely evaluation of spermograms, counting and issuing conclusions, studying lipid metabolism in blood serum. The patients were divided into 2 groups: the control group and the comparison group. Results. The qualitative and quantitative composition of seminal fluid has been established. In the control group, the quality of sperm in men was within normal parameters. In the comparison group, a decrease in the total number of spermatozoa, a decrease in their mobility and an increase in the percentage of abnormal spermatozoa were found in men with arterial hypertension in sperm. Lipid metabolism in the control group: “normolipidemia” was in 56 % of men and dyslipoproteidemia in 44 %. In the group with arterial hypertension (comparison group), 80 % of men had dyslipoproteidemia and normolipidemia in 20 % of infertile men. Conclusions: impaired reproductive function in men with arterial hypotension is associated with an increase in serum triglycerides and an increase in the amount of triglycerides in high-density lipoproteins.

Aim. To study the lipid profile in hospitalized patients with coronavirus disease 2019 (COVID-19) depending on the outcome of its acute phase according to the AKTIV international registry.Material and methods. The AKTIV registry included men and women over 18 years of age with a diagnosis of COVID-19, who were treated in a hospital. A total of 9364 patients were included in the registry, of which 623 patients were analyzed for levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides on days 1-2 of hospitalization. The level of high-density lipoprotein cholesterol (HDL-C) was calculated using the Friedewald equation.Results. We found that a decrease in LDL-C level was significantly associated with an unfavorable prognosis for hospitalized patients with COVID-19. This pattern persisted in both univariate and multivariate analyses. LDL-C levels in the final multivariate model had a significant relationship with the prognosis (an increase in the death risk by 1,7 times with a decrease per 1 mmol/l). In addition, we found that the survival of patients with an indicator level of

The review describes a number of competing views on the main causes of cholesterol accumulation in atherosclerotic vessels. On the one hand, unregulated cholesterol influx into arterial intima is primarily related to the increasing proportion of atherogenic lipoproteins in the lipoprotein spectrum of blood. On the other hand, the leading role in this process is assigned to the increased permeability of endothelium for atherogenic lipoproteins. The increased ability of arterial intima connective tissue to bind atherogenic blood lipoproteins is also considered to be the leading cause of cholesterol accumulation in the vascular wall. The key role in cholesterol accumulation is also assigned to unregulated (by a negative feedback mechanism) absorption of atherogenic lipoproteins by foam cells. It is suggested that the main cause of abundant cholesterol accumulation in atherosclerotic vessels is significant inflow of this lipid into the vascular wall during vasa vasorum hemorrhages.The article also provides arguments, according to which disorder of fatty acid metabolism in arterial wall cells can initiate accumulation of neutral lipids in them, contribute to the inflammation and negatively affect the mechanical conditions around the vasa vasorum in the arterial walls. As a result, the impact of pulse waves on the luminal surface of the arteries will lead to frequent hemorrhages of these microvessels. At the same time, adaptive-muscular intima hyperplasia, which develops in arterial channel areas subjected to high hemodynamic loads, causes local hypoxia in a vascular wall. As a result, arterial wall cells undergo even more severe lipid transformation. Hypoxia also stimulates vascularization of the arterial wall, which contributes to hemorrhages in it. With hemorrhages, free erythrocyte cholesterol penetrates into the forming atherosclerotic plaque, a part of this cholesterol forms cholesterol esters inside the arterial cells. The saturation of erythrocyte membranes with this lipid in conditions of hypercholesterolemia and atherogenic dyslipoproteinemia contributes to the process of cholesterol accumulation in arteries.

Aim. To study the lipid-lowering and pleiotropic vasoprotective effects of atorvastatin depending on the achievement of the target low-density lipoprotein cholesterol (LDL-C) level in patients after ST-segment elevation myocardial infarction (STEMI) within 48-week follow-up period.Material and methods. A total of 125 patients with STEMI, randomized to receive atorvastatin 40 or 80 mg per day for 48 weeks, were examined. On days 7-9, after 24, 48 weeks, we performed biochemical blood tests, echocardiography, as well as assessed the carotid arteries and endothelial function. The subjects were divided into the following groups: high-efficiency therapy (HET) — 41 patients who reached target LDL-C at control visits; moderate-efficiency therapy (MET) — 35 patients who achieved target LDL-C at one visit; low-efficiency therapy effective (LET) — 49 people who did not reach the target LDL-C. Differences were considered significant at p

Dyslipidemia makes a substantial contribution to the mortality as one of the leading pathogenetic factors for cardiovascular diseases. The nature and degree of the effect on the blood lipid spectrum may vary in the lipid-lowering drugs from different groups. Recently, a new class of PCSK9 inhibitors has been developed, which activity is associated with a protein involved in the low-density lipoprotein receptor control. In clinical practice, this group is represented by monoclonal antibody drugs evolocumab and alirocumab. The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are promising drugs to be used in the combination lipid-lowering therapy, which, given the results of clinical trials, can be recommended at this point on a third-priority basis after statins and ezetimibe. However, it is vital to indicate that these drugs have a sufficient safety profile, which makes it possible to prescribe these drugs in a triple combination adding it to the two first-line drugs regimen which patients had been given before. It is obvious that further study of PCSK9 will expand the range of their use for the treatment of familial hypercholesterolemia up to indications in cases where statins are limited and a more pronounced lipid-lowering effect is required to achieve target cholesterol levels.

Acute pancreatitis is a common non-communicable pathology in dogs, the untimely diagnosis and treatment of which is lethal (27-58% of cases). One of the most common medical tests for acute pancreatitis is to determine the concentration of triglycerides and other fractions of blood lipids. The purpose of the study was to investigate changes in lipid fractions and other biochemical parameters in dogs with acute pancreatitis. For the experiment, two groups of dogs of 10 individuals each were formed. The control group included healthy animals, the experimental group – dogs with acute pancreatitis. It was found that in dogs with acute pancreatitis, the concentration of triglycerides increased by 67% compared with healthy individuals. Cholesterol and phospholipid concentrations also increased by 23 and 9%, respectively. Inflammatory processes in the pancreas led to the development of cytolytic processes in its acini, as well as hepatocytes of the liver, as indicated by increased activity of indicator enzymes ALT, AST, LF and bilirubin. In addition, in sick dogs, the protein-synthesising function of the liver was impaired: a reduced proportion of albumin was registered against the background of increased total serum protein. Acute pancreatitis leads to a decrease in insulin synthesis, which is manifested by hyperglycaemia – in sick dogs, glucose levels are probably twice as high as in healthy animals. In pancreatitis, the violation of digestion and absorption of nutrients caused by intensive use of high-energy compounds (in particular, creatine phosphate) and an increase in creatinine (3.8 times). At the same time, the catabolism of proteins increased and the products of their intermediate and final metabolism – ammonia and urea – accumulated (by 60 and 57%, respectively), which is a sign of reduced filtration capacity of the kidneys. In addition, in acute pancreatitis within the physiological norm, the concentration of calcium decreased, and inorganic phosphorus – increased

The high prevalence of lipid metabolism disorders in the Russian population and their contribution to cardiovascular risk require an optimization of their pharmacotherapy in clinical practice.Aim. To study the possible benefits of statin therapy in fixed doses for primary and secondary prevention of cardiovascular disease in outpatient practice.Material and methods. Ambulatory patients (n=300) with a high or very high risk with hypercholesterolemia who had indications for statin treatment for primary or secondary prevention of cardiovascular diseases were included into a non-randomized trial. Patients were divided into 2 groups. Group 1 had a titration regimen of statins in accordance with current recommendations (group 1A [n=50] – primary cardiovascular prevention; group 1B [n=100] – secondary cardiovascular prevention). Group 2 received a titration-free statin regimen in fixed doses (group 2A [n=50] – primary cardiovascular prevention; group 2B [n=100] – secondary cardiovascular prevention). Patients were prescribed atorvastatin (10-80 mg/day) or rosuvastatin (10-40 mg/day). Group 1 patients had visits to the doctor after 1, 3, 6 and 12 months from the start of statin use, group 2 patients – after 3 and 12 months. Laboratory studies included determination of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c). Changes in lipid levels, the frequency of reaching target TC and LDL-c levels were evaluated.Results. Titration-free statins treatment (Group 2) allowed reaching the target levels of TC and LDL-c after 12 months in 73.9% and 56.3% of patients, respectively. Significant changes were found after 3 months visit. In Group 1, these indicators were slightly lower (56.8% and 53.4%, respectively), while significant changes in the LDL-c level were found later than in Group 2. More than 50% of patients taking statins for secondary prevention, reached the target level of TC and LDL-c. At the same time, when using titration-free statin therapy, such results were recorded after 3 months. Patients taking statins for primary prevention achieved the TC target level in 95.7% of cases (subgroup 2A). The frequency of reaching the LDL-c target level in the subgroups of primary prevention was slightly lower.Conclusion. The use of a titration-free statin treatment regimen allowed to more effectively control of TC and LDL-c levels in patients with high and very high cardiovascular risk compared to the traditional statin therapy regimen, and to achieve target lipid levels earlier.

Diagnosis of the blood pressure (BP) phenotype is the most important indication for its ambulatory measurement because BP phenotype is associated with cardiovascular complications and death. The study of BP phenotypes is important for patients with hypertension (HT) and comorbidity, including asthma and chronic obstructive pulmonary disease (COPD). The combination of HT with these lower airway diseases (LAD) leads to the mutual influence of pathologies creates difficulties in the drugs choice and may affect BP phenotype in HT patients.Aim. To compare in the prospective investigation various characteristics of BP phenotype in HT patients considering LAD (asthma or COPD).Material and methods. The prospective cohort study of ambulatory patients with HT (n=156) was carried out. The part of these patients had asthma or COPD (n=69). The clinical measurements and 24-hour BP monitoring, spirometry, clinical and biochemical blood tests, standard examination were performed, initially and after 12 months. BP phenotype were determined by the ratio of clinical BP and ambulatory BP considering their threshold values. Standard statistical methods and multivariate analysis were used.Results. Patients with LAD had 2 times more often prognostically unfavorable phenotypes: ineffective antihypertensive therapy (AHT) 37.3% vs 15.7% and masked AHT inefficiency 7.5% vs 4.5%; white coat HT on treatment (WCH) and effective AHT were less common(29.9% vs 42.7%; 25.5% vs 37.1%, respectively, p 148 mm Hg (b=2.733, p=0.040), LAD (b=1.015, p=0.011), serum total cholesterol (b=0.350, p=0.043), degree of nighttime diastolic BP decrease (for 13.1-18.0% b=-2.130, p=0.004; for 18.1-24.0% b=-2.509, p=0.001). The factors associated with masked AHT inefficiency in comparison to effective AHT were heart rate in orthostasis >87 beats/min(b=3,512, p=0.006) and SBP in orthostasis 141-148 mm Hg (b=3.405, p=0.004).Conclusion. The prevalence of prognostically unfavorable BP phenotypes (ineffective AHT and masked AHT inefficiency) is two times higher in HT patients with LAD. The first is associated with LAD presence, sex, and serum cholesterol; both phenotypes interrelated with hemodynamic parameters including degree of nighttime diastolic BP decrease. We found no association between AHT and LAD therapy with the BP phenotypes in this study. However, larger works in this area are required, including analysis of outcomes in long-term prospective studies.

High cholesterol level in serum (especially low-density lipoprotein cholesterol) is the risk factor of cardiovascular diseases. Thus, timely diagnosis and treatment of hypercholesterolemia in children is crucial. The basic treatment for children with hypercholesterolemia is diet therapy. This article analysed current recommendations on nutrition for children with hypercholesterolemia. Cholesterol dietary intake should be limited (< 200–300 mg/day), as well as saturated and hydrogenated fats (up to 8–10%). On the other hand, consumption of mono- (> 10%) and polyunsaturated fatty acids (up to 7–10% of the total dietary calories) should be increased. The need of complex carbohydrates consumption is stated, with the obligatory inclusion of soluble dietary fibres (pectin, inulin, mucus, gum) from fruits, vegetables, beans and whole grains with maintaining normal dietary calories.

BACKGROUND: Obesity is one of the most common children diseases. In present time it is being actively studied the natural hormones role in the pathogenesis of obesity. AIMS: To determine the relationship between serum nesfatin level with impaired lipid metabolism in school age children with overweight and obesity. MATERIALS AND METHODS: The study included children with overweight and obesity («case») and healthy children with normal body mass («control») aged 9 to 15 years. All children were determined by concentration in cholesterol blood and its factions, apoA-1, apoB. Enzyme-linked immunosorbent assay (Bio Human Nesfatin Enzyme Immunoassay Kit). RESULTS: Groups of patients with overweight and obesity (n = 53) and healthy children (n = 31) were comparable by age and sex. In obese children, a significant decrease in the level of nesfatin-1 was revealed compared with the group with normal body weight. In cases of children obesity there is a marked decrease in the concentration of nesfatin-1 in serum, especially expressed in the dyslipidemia presence. The nesfatin-1 level are negatively correlated to BMI and body fat content. CONCLUSIONS: The obtained data suggest that along with the known key role of nesfatin in the regulation of eating behavior and appetite, it also affects anthropometric indicators, primarily associated with the accumulation of excess fat mass. Based on the data obtained, nesfatin-1 should be considered as a possible marker for the development of obesity in children.

Disclaimer РThe EAC/RNAS Guidelines represent the views of the EAC and RNAS, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC and RNAS is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC/RNAS Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC/RNAS Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC/RNAS Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC/RNAS Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.Members of the Working Group confirmed the lack of financial support / conflict of interest. In the event of a conflict of interest being reported, the member (s) of the Working Group was (were) excluded from the discussion of sections related to the area of conflict of interest.

New effective economic microbial test-system for screening of microbial metabolites, that are inhibitors of sterol biosynthesis, is proposed. It is based on cultivation of fungal strain Acremonium fusidioides (former Fusidium coccineum), that produces fusidic acid (fusidin) that is antibiotic of steroid structure. Great similarity of fusidic acid biosynthesis in fungous strain and cholesterol biosynthesis in human organism, coincidence of their initial steps till squalene formation, allows use A. fusidioides as a model for estimation of microbial secondary metabolites that are potential inhibitors of sterol biosynthesis. Such inhibitors in A.fusidioides model are revealed as compounds that strongly reduce fusidin production without any visible influence on fungus growth. Mevalonate that is one of the crucial intermediates of sterol biosynthesis could be successfully applied for removal of inhibition induced by some microbial metabolites. A.fusidioides test-system can be easily mechanized because of miniaturization of microbiological procedures, cultivation in 6-, 24-, or 96-well plates and usage of automatic micropipettes and dispensers. The results of this model are well correlated with the ones obtained with human cells (Hep G2 test-system, offered earlier). A.fusidioides test-system can be applied at rather early stages of screening procedures and is quite effective for testing of crude extracts of producers' culture liquid.

Aim. To study the prevalence of the main risk factors for cardiovascular diseases in young ethnic Europeans and Koreans permanently residing in the Primorsky Krai.Material and methods. The data of the ethnic Europeans (group 1) were taken from the ESSE-RF multicenter epidemiological study conducted in the Primorsky Krai (n=911); group 2 included ethnic Koreans (n=106), who underwent all clinical and laboratory tests used in ESSE-RF study. Subjects of both groups did not have cardiovascular disease. Biochemical assessment included total cholesterol (TC), low- and high-density lipoproteins (LDL and HDL), triglycerides (TG), apolipoprotein B (apoB) and A (apoA), lipoprotein (a), glucose, uric acid (UA) and creatinine. Both groups were divided into subgroups depending on the status of smoking and compared among themselves. Statistical processing included the Mann-Whitney test, the Kruskal-Wallis test and chi-squared test.Results. Both groups were in the same age range (p=0,44). The prevalence of smoking was 24,3% and 28,3% for the ethnic Europeans and Koreans, respectively (p=0,22). Among the European population, a higher body mass index (p>0,05) was noted. Systolic and diastolic blood pressure did not statistically differ (p>0,05), resting heart rate was significantly higher in group 1 (p0,05) between groups. In group 2, glucose, creatinine and UA values also had higher values (p0,05).Conclusion. It was shown that young ethnic Koreans had a higher values of laboratory parameters associated with cardiovascular risk (CVR) compared with ethnic Europeans, which should be taken into account when assessing CVR and requires the correction of preventive measures for cardiovascular disease. It was found that the body mass index is higher among active and former smoking in both cohorts compared with never smokers. Active and former smokers of the European ethnic group had a significantly lower apoA and HDL-C levels and higher TG and UA values. Thus, the study demonstrates the need to individualize the CVR assessment in people of different ethnic groups living in the same territory and to take into account the smoking status of both active and former smokers.

The mechanisms of epileptiform neuronal activity development under blood-brain barrier (BBB) dysfunction remains relevant in modern psychoneurology. In the present work we mimic some effects of BBB disruption in the culture of hippocampal neurons to examined the effect of serum-adapted ionic environment on the impulse activity of hippocampal neurons and the role of serum protein thrombin in induction of epileptiform neuronal activity. Using the whole-cell patchclamp method under current-clamp mode we analyzed the spontaneous action potentials (AP) in the single hippocampal neurons. The changing of ionic extracellular neuronal environment to such serum-adapted contributed to the development of epileptiform tonic activity of cultured hippocampal neurons and led to increase the average APs frequency by 65.1 ± 17.9% (n = 5) in neurons with spontaneous firing activity (FA) and to occurrence of tonic electrical activity (1.65 ± 0.4 s-1) in neurons without firing activity. Glutamate NMDA receptors significantly contribute to epileptiform tonic activity formation in neurons with FA, while their role in tonic activity providing in neurons without FA was insignificant. Thrombin (5 U/ml) in the serum-adapted ionic solution significantly enhanced of epileptiform activity in neurons with and without spontaneous FA: APs frequency increased in these neuronal groups by 117.3 ± 25.6% (n = 3) and by 61.8 ± 11.5% (n = 3), respectively, compared with that in the serum-adapted ionic solution only. Blockade of thrombin protease activated receptor 1 (PAR-1) by application of SCH 79797 (10 μm) canceled the thrombin's effect in neurons without spontaneous FA, and significantly reduced such in neurons with FA. Therefore, the change of ionic extracellular neuronal environment to serum-adapted stimulates the occurrence of epileptiform activity in hippocampal neurons, that is apparently associated with NMDAreceptors activation in neurons with FA. The proepileptiform action of thrombin was mostly mediated by PAR-1 activation. Thrombin-dependent regulation of the hippocampal single neurons firing activity involves the mechanisms different from the modulation of glutamate NMDA receptors in these cells. [ABSTRACT FROM AUTHOR]

The article discusses different points of view on atherosclerosis development. The facts confirming the lipid hypothesis are presented. Attention is drawn to the possible participation of vasa vasorum in the development of atherosclerosis.

The review discusses atherosclerosis-related mechanisms of car-diovascular disease development, as well as the optimization of their prevention and treatment methods. Recent experimental and clinical studies have shown the important role of vascular endothelium in the development and progression of atherosclerosis. Myocardial ischemia, activation of free-radical processes and impaired bioenergetics initiate a decrease in production of nitric oxide, which plays major vasodilator role. In this regard, the scientists is interested in the search for new drugs that can affect the main pathogenetic links of coronary artery disease. Statins are currently the drugs of choice. However, they are not always effective and have an ambiguous effect on oxidative potential of myocardial cells and endothelial function. Moreover, inhibition of mevalonic pathway for cholesterol synthesis is accompanied by a deficiency of coenzyme Q10, which is the central cellular antioxidant that protects phospholipids of cell membranes from free radicals. Rationale of using coenzyme Q10 in the complex treatment and secondary prev ention of cardiovascular diseases, including coronary artery di sease, is discussed.

The search for early markers of atherosclerosis is an effective method for providing personalized medicine allowing the prevention of the progression of this pathology. The aim of this study was the determination of the total indices of dyslipidemia and the identification of the gender indices of the extended lipid profile in the population of residents of the Southern and Central Federal Districts (Voronezh, Belgorod, Lipetsk, Kursk and Rostov regions) for the identification of early markers of atherogenicity. In a simultaneous clinical study, involving 339 patients (mean age 48 years), the concentrations of total cholesterol, triglycerides, LDL (low density lipoproteins), HDL (high density lipoproteins), apolipoproteins B and A1, the ApoB/ApoA1 ratio and the atherogenic coefficient were determined. For the identification of the relationship between changes in lipid profile indicators with cytolysis syndrome and indicators of carbohydrate metabolism, the activity of ALAT (alanine aminotransferase), GGTP (gamma-glutamyl transpeptidase) and glucose content were also studied. Analysis of the results of the lipid spectrum of the population sample of the middle age group revealed significant metabolic disorders of lipid metabolism with a predominance of atherogenic lipid fractions and a significant excess of indicators of atherogenic lipid fractions in middle-aged men in comparison with women. It has been shown that the apoB/apoA1 index can be used as an auxiliary marker for early assessment of the prevalence of atherogenic lipid fractions, allowing the identification of risk groups for the development of diseases associated with metabolic disorders

The aim. To study changes in the indices of carbohydrate-lipid metabolism and antioxidant protection in metabolic syndrome with arterial hypertension and abdominal obesity depended on climatic factors in Azerbaijan. Methods. We examined 16 patients with newly diagnosed arterial hypertension with abdominal obesity on the background of the metabolic syndrome aged 25 to 70 years (16 men). To study the components of carbohydrate, lipid metabolism and antioxidant protection in patients, blood was collected from the cubital vein after a 12-hour fast. The study of the parameters of the general blood test performed on the apparatus Mythic 18 (Switzerland). The levels of glucose, glicohemoglobin, C-peptide, insulin, cholesterol, low-density lipoproteins, high-density lipoproteins, triglycerides, malondialdehyde, and the activity of superoxide dismutase enzymes, catalase, and interleukin-8 studied. Results. The insulin level in the blood plasma of patients compared with the control group showed a significant increase in the studied parameter in this pathology. Despite the fact that glucose and insulin in the control group were 4,58±0,15 mM/l and 16,2±0,6 uU/ml, with this pathology, statistically significantly increased and became 5,58±0,26 mM/l and 18,3±0,7 uU/ml. The content of glucose in patients varied in the reference range. The average value of this parameter was close to the threshold value (5.58±0.26 mM/l), which signals the need to monitor blood sugar levels. Despite the fact that glycohemoglobin did not undergo changes, the content of C-peptide increased compensatory. Compared to the control group, cholesterol increased by 43.5% p

Aim. To assess the efficacy and safety of plant stanols in patients with arterial hypertension (AH) and disorders of lipid metabolism, without clinical manifestations of atherosclerosis.Material and methods. The study included 40 patients — men at the age of 50-55 years, with AH (stage 1) and cholesterol above 5,0 mmol/l and LDL cholesterol above 3,0 mmol/l with low and medium risk (SCORE — 1-4%). Patients with coronary artery disease and other clinical manifestations of atherosclerosis, secondary hypertension, liver diseases, diabetes mellitus, secondary dyslipoproteinemia, cardiovascular diseases requiring constant therapy, bronchial asthma were excluded from the study. Patients were randomized into 2 groups of 20 people. In the study group of patients within 3 months received plant stanols (2 tab./day), in the control group — only healthy diet. In addition, patients with high blood pressure received antihypertensive therapy. Assessment of lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) was performed at baseline and after 3 months. At the beginning of the study, after 3 months of the study patients underwent a full medical examination. Safety control of plant stanols was carried out by determination of liver enzymes (aspartic transaminase (AST), alanine transaminase (ALT)), before and after the completion of the study.Results. Patients of two groups were comparable in baseline characteristics (lipid parameters, blood pressure level). After 3 months of research beginning patients from study group have statistically significant decrease of total cholesterol and LDL cholesterol. The average level of total cholesterol before treatment was 5,8±0,32 mmol/l, and after treatment — 5,3±0,32 mmol/l, p

The aim of the study is to determine a lipid spectrum of blood plasma and liver in rats in with simulated dyslipidemia against the background of the administration of the fatty oil extract from the seeds of Nigella damascena L.Materials and methods. Laboratory animals – Wistar male rats – were used in the work. To study the hypolipidemic activity, such models as acute Tween, subchronic vitamin-D2 models and a model of chronic heart failure were used. The identifiable parameters were the concentration of cholesterol and triglycerides in the blood serum and liver, as well as the concentration of atherogenic and non-atherogenic lipoproteins in the blood serum, and the atherogenic coefficient.Results. As a result of the study, it was found out that a course administration of the fatty oil extract from the seeds of Nigella damascena L. against the background of simulated chronic heart failure (CHF) by the right ventricular type, normalizes the lipid spectrum of the experimental animals’ blood serum, causing an increase in the concentration of high-density (non-atherogenic) lipoproteins, and reduces the concentration of low-density (atherogenic) lipoproteins. A single administration of the fatty oil extract from the seeds of Nigella damascena L. promotes the correction of lipid metabolism disorders under the conditions of acute Tween lipidopathy, while the direction of the object being studied reduces the concentration of cholesterol and triglycerides in the liver and blood serum under the conditions of subchronic dyslipidemia. At the same time, the effect of the use of the fatty oil extract from the seeds of Nigella damascena L. was not inferior to “Omaсor”, the reference drug.Conclusion. The possibility of using a fatty oil extract from the seeds of Nigella damascena L. for preventive and therapeutic aims in cardiovascular diseases has been established.

The hypothesis regarding the relationship between Helicobacter pylori infection and the development of arteriosclerosis is not clearly demonstrated and needs validation even though many clinical trials conducted in this area in recent years seem to support this etiopathology. H. pylori is a Gram-negative, microaerophilic bacterium, usually found in the stomach, widespread in the environment. Infections often occurs even in early childhood. As a result of infection a chronic inflammation develops with concomitant elevated levels of C-reactive protein (CRP). It has long been known that atherosclerosis is a chronic disease of the arteries with underlying inflammation. The formation of atherosclerotic plaques may also begin in childhood. There are more than one mechanism that may affect disease development. Lipopolysaccharides of H. pylori by stimulating the secretion of Tumor Necrosis Factor (TNF) by macrophages inhibits lipoprotein lipase activity, which results in an increase in serum triglycerides and a decrease in serum High-density Lipoprotein (HDL) cholesterol. The second mechanism leading to an increased risk of arteriosclerosis may be associated with a chronic inflammation of the gastric mucosa which may lead to impaired absorption of many nutrients, including vitamins B6, B12 and folic acid, the deficiency of which results in secondary hyperhomocysteinemia. Elevated levels of homocysteine ​​are a strong risk factor for atherosclerosis. Lastly, in the serum of patients with H. pylori infection, elevated values ​​of number of important factors from the point of view of atherosclerotic plaques formation are found. These include CRP, interleukin 6 (IL-6), interleukin 8 (IL-8), TNF-α, fibrinogen, type 1 plasminogen tissue activator inhibitor and Willebrand factor. Taking into account the above-mentioned correlations, it seems reasonable to continue research focusing on many pathomechanisms that may help explaining the cause and relationship of H. pylori infection to the development of atherosclerosis. Clinical trials conducted on the pediatric population, could contribute to the broadening of medical knowledge in this area, as well as to the modification of preventive and therapeutic recommendations for atherosclerosis and its consequences.

In this article we presented study results characterizing the lithogenicity changes in cases with biliary tract obstruction based on assessment of lipidic exchange indicators and condition of pro-oxidant – antioxidant activity at the local level. It is determined that in group with primary choledocholithiasis we observed decrease of anti-oxidizing activity by 47.1%, in the absence of reliable changes of intensity for free radical oxidation, rise of general lipids level to 9.9% at simultaneous lack of authentic changes of cholesterol content which are followed by ascending integrated lithogenicity index indicator in average for 59.7%. Besides, it has been shown that in patients with a recurrence of mechanical jaundice (in terms from 2 to 7 months) integrated indicator of lithogenicity index was very high at primary assessment (16.27 U). The possibility to research metabolic disturbances expression for various diseases of a biliopancreatoduodenal area at the local level on the basis of an integrated lithogenicity index indicator allowed to optimize an algorithm for the choice of the biliary tract decompression referred on early endoprosthetic incrustation and also to provide adequate techniques for patients management postoperatively and prove the necessity of performing the certain treatment referred to prophylaxis of the remote complications of endobiliar stenting.

The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is now considered an important contributor to the pathogenesis of atherosclerosis. The article describes the history of the discovery of PCSK9, the structure, functions and stages of biosynthesis of this molecule. PCSK9, through promoting lysosomal degradation of hepatic low-density lipoprotein receptor (LDLR), can decrease the clearance of plasma LDL, leading to hypercholesterolemia and formation atherosclerotic plaque formation. PCSK9 is a new therapeutic target for the treatment of hypercholesterolemia. New lipid-lowering drugs – PCSK9 inhibitors – are more effective than statins. Some studies have shown the involvement of PCSK9 in the inflammatory mechanisms of atherosclerosis.

Tere are 44 patients (5 males and 39 females), aged 56 to 90 years were included in the study. To assess the tolerability and safety of the drug, undesirable events were recorded, associated and not associated with taking the drugwith taking the drug, a physical examination of patients was performed, an ECG was recorded and a biochemical blood test was performed at each visit of the patient to the center. During the observation period, two undesirable events chronologically associated with taking the drug were recorded During the study, none of the patients was excluded from the program due to the development of side effects and none of the patients refused to take the drug. We did not fnd any statistically signifcant increase in the incidence of cardiac pathology in patients taking the study drug, nor worsening of the already existing symptoms on the background of taking the drug for six months. Te observed growth trends in the level of blood creatinine a give grounds to recommend monitoring of kidney function in the patients taking the drug. In general, noogerone showed good tolerability, despite the elderly age of its patients and the high prevalence of concomitant somatic diseases in the sample.

Background. The genetic nature of a comorbid development of obesity and arterial hypertension (AH) in children is poorly studied. In this regard, it is important to study genes, the polymorphism of which is associated with disturbances in both metabolic processes and control of arterial pressure. Objective. Our aim was to study the association of polymorphisms P12A (rs1801282) of the PPARG gene, G75A (rs670) of the apolipoprotein A1 gene (APOA1), C112A (rs429358) and A158C (rs7412) of the apolipoprotein E gene (APOE) with the development of obesity and AH in children. Methods. The study included children with obesity and AH (case) and healthy children (control) aged from 10 to 17 years. Gene polymorphism was studied by polymerase chain reaction in real time. We determined blood concentrations of cholesterol and its fractions, triglycerides, apoA1, apoB, fasting glucose and glucose tolerance test for all children. Results. Groups of patients with obesity and AH (n = 69) and healthy children (n = 49) were comparable by age and sex. In the case group, there were more carriers of the A allele (25 versus 9% in the healthy group; p = 0.002) and the AA genotype (13% and 2%, respectively; df = 2, p = 0.031) of APOE C112A polymorphism. PPARG and APOA1 polymorphisms as well as APOE A158C polymorphism were not associated with the development of obesity and AH in children. The carriers of the APOE e2 allele had lower concentrations of low density lipoproteins and apoB in the blood; the carriers of the PPARG G allele had lower glycemia values, and the carriers of the A allele of APOA1 G75A polymorphism had higher glycemia values. Conclusion. The APOE C112A polymorphism is associated with a comorbid development of obesity and AH in children. The pathogenetic significance of PPARG and APOA1 polymorphisms warrants further investigation.