Charge carrier transport in PbS films doped with iodine.

The results of the measurements of electrical and Hall resistivities on polycrystalline PbS films doped with iodine obtained through hydrochemical deposition are presented. The analysis of the temperature dependence of resistivity points out the crossover from the hopping mechanism due to thermal delocalization in the impurity band to the variable range hopping mechanism. The increase in the iodine content in the films leads to an increase in the impurity ionization energy. It has been established that the temperature dependence of resistivity over a wide temperature range obeys the inverse Arrhenius law, which is characteristic of disordered polycrystalline films with different sizes and orientations of crystallites relative to the substrate, as confirmed by AFM topography, Raman spectra and X-ray diffraction measurements. We found that the type of charge carrier changes from electrons to holes with an increase in the iodine content. Additionally, for a wide range of iodine doping, the concentration of charge carriers is low, indicating the possible occurrence of a self-compensation mechanism due to the formation of impurity defects.

The Clinical Evolution of Diffuse Myocardial Fibrosis in Patients With Arterial Hypertension and Heart Failure With Mildly Reduced Ejection Fraction Treated by Olmesartan or Sacubitril / Valsartan.

Aim      A 12-month evaluation of the potentialities of the angiotensin II receptor inhibitor olmesartan (Olme) and the angiotensin receptor and neprilysin inhibitor (ARNI) sacubitril/valsartan in patients with arterial hypertension (AH) and dyslipidemia in the dynamics of the following indicators of chronic heart failure (CHF): N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), LV global longitudinal strain (LV GLS) in diffuse myocardial fibrosis (MF) previously diagnosed by magnetic resonance imaging (MRI).Material and methods  Olmesartan medoxomil (n=56) and sacubitril/valsartan (n=63) were used for 12 months in patients with hypertension, dyslipidemia and NYHA functional class II-III CHF with mid-range LVEF (CHFmrEF). MF was diagnosed by the following MRI criteria: late gadolinium enhancement and an increased proportion of extracellular matrix (33% or more). The frequency of persisting late gadolinium enhancement and the increased proportion of extracellular matrix (33% or more) was evaluated at 12 months; changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), NT-proBNP, and LV GLS were evaluated after 3, 6, and 12 months of follow-up.Results Baseline parameters did not differ between groups. The late gadolinium enhancement and increased proportion of extracellular matrix were present at baseline in all patients of both groups (100%; p=1.0). Already at 3 months, statistically significant decreases in SBP and DBP were observed in both groups. In addition, the LV GLS monitoring showed LV GLS significantly increased in both groups after 3 months and continued changing after 6 and 12 months. The NT-proBNP concentration significantly decreased in both groups already after 3 months and continued to decrease after 6 and 12 months. At 6 and 12 months, sacubitril/valsartan was superior to olmesartan in reducing SBP and NT-proBNP and in restoring LV GLS. At 12 months, the incidence of persisting, abnormal late gadolinium enhancement and increased proportion of extracellular matrix was significantly less in the ARNI group.Conclusion      Olmesartan was demonstrated effective in the multi-modality therapy of CHFmrEF and MF in patients with AH and dyslipidemia. ARNI was superior to olmesartan in this regard, but further research of this issue is required.

[Efficacy and safety of the use of alirocumab in real clinical practice].

AIM: To evaluate the results of two-year use of alirokumab in Karelia Republic. MATERIALS AND METHODS: The observation group consisted of 27 patients (17 patients with familial hypercholesterolemia, 10 patients with the history of myocardial infarction), mean age 53.4±4.3 years, 70.3% men, follow-up duration from one year to 2.5 years, 18 (66.6%) patients received therapy for more than 2 years. 19 patients received alirocumab at a dose of 75 mg/ml once every 2 weeks, eight - at a dose of 150 mg/ml once every 2 weeks. Before the start of therapy, the majority received maximally tolerated statin therapy, 10 patients received statin therapy in combination with ezetemibe, 3 patients received ezetemibe monotherapy due to statin intolerance. The target levels of LDL cholesterol were considered for very high risk patients less than 1.4 mmol/L, high risk - less than 1.8 mmol/L, extreme risk - less than 1 mmol/L. RESULTS: The reduction of LDL on therapy with alirocumab was 58%; target levels of LDL were achieved in 77.8%. The level of decrease in LDL cholesterol less than 50% was noted only in 7.4% of cases. Patients requiring a large dose of the drug were classified as very high risk, had higher cholesterol and LDL-C levels. The level of Lp(a) decrease on 29.7% by 6-12 months. No destabilization of coronary heart disease, new cases of stroke were registered. CONCLUSION: The inclusion of alirocumab in the treatment regimen contributed to the stable course of atherosclerosis-associated diseases, the achievement of LDL cholesterol targets in 77.8% of patients, was not accompanied by side effects during 2.5 years therapy.

MTNR1A and MTNR1B Gene Variants of the Melatonin Receptor and Arterial Stiffness in Persons without Arterial Hypertension.

A comparative analysis of vascular stiffness indices and the results of blood test was carried out in 85 healthy donors aged 19-64 years, carriers of polymorphic variants of type 1 and type 2 melatonin receptor genes. The associations of polymorphic markers of type 1 MTNR1A (rs34532313) and type 2 MTNR1B (rs10830963) melatonin receptor genes with parameters of vascular stiffness and blood parameters in healthy patients were studied. Genotyping was performed using allele-specific PCR. In all patients, 24-h BP monitoring with assessment of arterial stiffness was performed. Allele C homozygotes of MTNR1A differed significantly from carriers of the major T allele by elevated triglyceride, LDL, and fibrinogen levels. The major allele C of the rs10830963 polymorphic variant of the MTNR1B gene is associated with elevated LDL and triglycerides, as well as with individual differences in the elastic properties of the vascular wall in the examined subjects.

[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

BACKGROUND: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI). AIM: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period. MATERIALS AND METHODS: AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected  the  data  of  hospitalized  patients  and  included  3  visits.  All  subjects  were  divided  into  3  groups:  not  overweight  (n=2139), overweight (n=2931) and obese (n=2666). RESULTS: A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (p<0.001), serum C-reactive protein over 100 mg/l (p<0.001), and the need for targeted therapy (p<0.001) in the hospitalized patients. Obesity increased the odds of myocarditis by 1,84 times (95% confidence interval [CI]: 1,13-3,00) and the need for anticytokine therapy by 1,7 times (95% CI: 1,30-2,30).The  patients  with  the  1st  and  2nd  degree  obesity,  undergoing  the  inpatient  treatment,  tended  to  have  a  higher  probability  of  a  mortality  rate.  While  in  case  of  morbid  obesity  patients  this  tendency  is  the  most  significant  (odds  ratio  -  1,78; 95% CI: 1,13-2,70). At the same time, the patients whose chronical diseases first appeared after the convalescence period, and those who had certain complaints missing before SARS-CoV-2 infection, more often had BMI of more than 30 kg/m2 (p<0,001).Additionally, the odds of death increased by 2,23 times (95% CI: 1,05-4,72) within 3 months after recovery in obese people over the age of 60 yearsCONCLUSION.  Overweight  and/or  obesity  is  a  significant  risk  factor  for severe  course  of  the  new  coronavirus  infection  and  the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

Analysis of Clinical and Biochemical Characteristics of Patients With Genetically Confirmed Familial Hypercholesterolemia in Russian North Western District Residents.

Aim      To compare results of clinical, laboratory, and genetic examination of patients with familial hypercholesterolemia (FHC).Material and methods  112 patients aged 40.2±17.9 years (49 men) were examined. The gene of low-density lipoprotein receptor (LDLR) was analyzed and evaluated using the Dutch Lipid Clinic Network (DLCN) criterion of lipid score ≥6. The LDLR gene mutation was searched for using the conformational polymorphism analysis followed by sequencing of the DNA of isolated LDLR gene exons.Results Mean variables of the blood lipid profile were total cholesterol (C), 10.12±2.32 mmol/l, LDL-C, 7.72±2.3 mmol/l. Corneal arcus was observed in 15 % of patients, tendon xanthomas in 31.8 %, and xanthelasma palpebrarum in 5.3 %. The types of LDLR gene mutations included missense mutations (42.8 %), mutations causing a premature termination of protein synthesis (41.1 %), and frameshift mutations (16.1 %). In the presence of a mutation in exon 4, patients with IHD compared to patients with no IHD had significantly higher levels of total C (10.88±2.08 mmol/l vs. 8.74±1.57 mmol/l, respectively, р=0.001) and LDL-C (8.60±2.14 mmol/l vs. 6.62±1.79 mmol/l, respectively, р=0.005). Patients with IHD compared to patients with no IHD and a mutation in LDLR gene exon 9 had only a higher LDL-C level (8.96±1.53 mmol/l vs. 6.92±1.59 mmol/l, respectively, р=0.022). A differentiated comparison of IHD patients using a logistic regression depending on the identified type of LDLR gene mutation produced formulas for calculating the odds ratio of IHD and myocardial infarction (MI) with adjustments for the patient's age and baseline LDL.Conclusion      The detection rate of the LDLR gene mutations was 42.8 % for missense mutations, 41.1 % for mutations causing a premature termination of protein synthesis, and 16.1 % for frameshift mutations. Blood lipid profiles did not differ between patients from different cities and with different types of LDLR gene mutations. Blood lipid profiles were different in IHD patients depending on the mutation type.

[ACTIV SARS-CoV-2 registry (Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients). Assessment of impact of combined original comorbid diseases in patients with COVID-19 on the prognosis].

AIM: Study the impact of various combinations of comorbid original diseases in patients infected with COVID-19 later on the disease progression and outcomes of the new coronavirus infection. MATERIALS AND METHODS: The ACTIV registry was created on the Eurasian Association of Therapists initiative. 5,808 patients have been included in the registry: men and women with COVID-19 treated at hospital or at home. CLINICALTRIALS: gov ID NCT04492384. RESULTS: Most patients with COVID-19 have original comorbid diseases (oCDs). Polymorbidity assessed by way of simple counting of oCDs is an independent factor in negative outcomes of COVID-19. Search for most frequent combinations of 2, 3 and 4 oCDs has revealed absolute domination of cardiovascular diseases (all possible variants). The most unfavorable combination of 2 oCDs includes atrial hypertension (AH) and chronic heart failure (CHF). The most unfavorable combination of 3 oCDs includes AH, coronary heart disease (CHD) and CHF; the worst combination of 4 oCDs includes AH, CHD, CHF and diabetes mellitus. Such combinations increased the risk of lethal outcomes 3.963, 4.082 and 4.215 times respectively. CONCLUSION: Polymorbidity determined by way of simple counting of diseases may be estimated as a factor in the lethal outcome risk in the acute phase of COVID-19 in real practice. Most frequent combinations of 2, 3 and 4 diseases in patients with COVID-19 primarily include cardiovascular diseases (AH, CHD and CHF), diabetes mellitus and obesity. Combinations of such diseases increase the COVID-19 lethal outcome risk.

[The combination of recurrent otitis media and adenotomy in early childhood as diagnostic marker of mucopolysaccharidosis type II (Hunter syndrome)]. / Sochetanie retsidiviruyushchego srednego otita i adenotomii v rannem detskom vozraste kak diagnosticheskii marker mukopolisakharidoza II tipa (sindroma Khantera).

Mucopolysaccharidoses are a group of rare lysosomal accumulation diseases caused by a deficiency of the lysosomal enzyme and the accumulation of mucopolysaccharides in various organs and tissues. Children with mucopolysaccharidosis type II (Hunter syndrome) develop multisystem dysfunction, including severe airway obstruction. At the same time, 34% of patients already at an early age (2-3 years) undergo surgical manipulations related to ENT organs (tonsillectomy, adenotomy). The article describes a clinical case of diagnosis of type II mucopolysaccharidosis by a pediatric otorhinolaryngologist. The main manifestations of the disease are discussed in detail, including the presence of indications for adenotomy at the age of 2 years, episodes of otitis media, which served as diagnostic markers for suspected orphan disease mucopolysaccharidosis type II. The leading role of the pediatric otorhinolaryngologist in the early diagnosis of the rare disease mucopolysaccharidosis type II is substantiated.

Modern aspects of burn injury immunopathogenesis and immuno-biochemical markers of wound healing (review of literature).

Burns are one of the most common traumatic injuries in the world, representing a global public health problem. Major burns (severe burn injury or burn disease) are one of the most life-threatening injuries. There is a great need to identify and monitor the development of complications (sepsis and septic shock, coagulopathy and DIC) in burned patients. The basis of the pathogenesis of burn injury, as well as any general pathological process, is an inflammatory reaction, ultimately aimed at restoring the structure and function of the damaged tissue. A feature of the inflammatory reaction in burn injury is the scale of alteration of the skin and mucous membranes. The review presents the main aspects of the burn injuries immunopathogenesis and the features of post-burn immune dysfunction, manifested by disorders in the innate and adaptive immunity systems. Attention is focused on the role in the immunopathogenesis of developing systemic and local disorders in burn injury. Also the role are discussed of a minor subpopulations of lymphocytes (Treg-, Th-17-, γδT-cells) in the immunopathogenesis and in the bacterial infection protection. The characteristics of the main immuno-biochemical markers of burn injury (cytokines and growth factors, nitric oxide, matrix metalloproteases, bacteria concentration levels) are present. The prognostic role of these biomarkers in assessing of the severity degree of patients with burn injury and wound healing processes is shown. The review has been compiled using references from major databases such as RSCI, Web of Science, PubMed, Scopus and Google Scholar (up to march 2022). After obtaining all reports from database, the papers were carefully analyzed in order to find data related to the topic of this review (60 references).

Monomeric form of C-reactive protein in the assessment of the residual inflammatory cardiovascular risk in patients with subclinical carotid atherosclerosis.

Aim      To study the relationship between monomeric C-reactive protein (mCRP) and the progression of asymptomatic carotid atherosclerosis in patients with a moderate risk for cardiovascular diseases (CVD) as assessed with the SCORE model.Material and methods  The study included 80 men and women aged 53.1±5.8 years assigned to the category of a moderate risk for CVDs by the SCORE model with a low-density lipoprotein cholesterol (LDL-C) level of 2.7-4.8 mmol/l and asymptomatic, hemodynamically insignificant (<50% luminal narrowing) carotid atherosclerosis according to ultrasonic data. All patients were prescribed atorvastatin to achieve a LDL-C level <2.6 mmol/l. After 7 years of follow-up, ultrasonic examination of carotid arteries was performed, and concentrations of high-sensitivity C-reactive protein (hsCRP) and mCRP were measured.Results A concentration of LDL-C <2.6 mmol/l was achieved in all patients. The progression of atherosclerosis as determined by an increased number of atherosclerotic plaques (ASPs), was observed in 45 (56 %) patients. At 7 months of follow-up, concentrations of cCRP were higher in the group of patients with progressive carotid atherosclerosis, while the levels of hsCRP did not differ between the groups. Increased mCRP concentrations were associated with changes in variables of the "atherosclerotic load", including the number of ASPs, total ASP height, and the intima-media thickness (IMT). In patients with a median mCRP concentration of 5.2 [3.3; 7.1] µg/l and more, the increases in mean ACP number and total ASP height were considerably higher than in patients with mCRP concentrations lower than the median (3.9 and 2.7 times, respectively), whereas the odds ratio for the progression of asymptomatic carotid atherosclerosis was 5.5 (95 % confidence interval, CI: 2.1-14.6; p=0.001). ROC analysis showed that the concentration of hsCRP had no predictive value for prognosis of asymptomatic carotid atherosclerosis (p=0.16), while the area under the ROC curve (AUC) for mCRP was 0.75±0.056 (95 % CI: 0.64-0.86; p=0.001).Conclusion      According to the results of 7-year follow-up, the plasma concentration of mCRP was significantly higher in patients with an increased number of ASPs than in patients without this increase. An increased level of mCRP may indicate a higher inflammatory risk of CVD.

[Case of peripartum cardiomyopathy misdiagnosed as pulmonary changes due to COVID-19].

A 37-year-old female patient was admitted 16 days after delivery in a hospital for infectious diseases with cough, shortness of breath, and infiltrative changes in the lungs that were interpreted as viral pneumonia. Considering the failure of therapy and the history, peripartum cardiomyopathy was suspected. Examination revealed a decrease in left ventricular ejection fraction to 30 %, ultrasonic signs of lung congestion and bilateral hydrothorax. The patient was diagnosed with peripartum cardiomyopathy accompanied by functional class 4 heart failure. A specific feature of this case was fast positive dynamics with complete regression of the clinical picture of congestion and improvement of the left ventricular myocardial function associated with the treatment.

Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2¼).

Aim      To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods  The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients' privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).Results The analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion      In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

[International register "Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients (ACTIV SARS-CoV-2)"].

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[The prognostic value of high-sensitivity C-reactive protein blood level after coronary stenting for the development of stent restenosis].

Aim      To analyze the relationship between serum concentrations of high-sensitivity C-reactive protein (hsCRP) in dynamics and development of restenosis at 12 months following elective coronary stent placement (CSP).Material and methods  The key role in atherogenesis, neointimal proliferation and restenosis belongs to inflammation. This study included 91 patients (median age, 60 [56; 66] years) with stable exertional angina after an elective CSP using second-generation stents. Follow-up coronarography was performed for 60 patients at 12 months. Concentration of hsCRP was measured immediately prior to CSP and at 1, 3, 6, and 12 months after CSP. Restenosis of the stented segment (50% or more narrowing of the stented segment or a 5-mm vessel segment proximally or distally adjacent to the stented segment) was observed in 8 patients.Results According to results of the ROC analysis, the increase in hsCRP concentration >0.9 mg/l (>25%) at one month after CSP had the highest predictive significance with respect of restenosis (area under the ROC curve, 0.89 at 95 % confidence interval (CI) from 0.79 to 0.99; sensitivity, 87.5 %; specificity, 82.8 %; р=0.0005), which was superior to the absolute value of hsCRP concentration >3.0 mg/l (area under the ROC curve, 0.82 at 95 % CI from 0.68 to 0.96; р=0.0007).Conclusion      Increased concentration of hsCRP ≥0.9 mg /l (≥25 %) at a month after CSP was associated with restenosis of the coronary artery stented segment.

[Experience of the use of the PCSK9 inhibitor Alirocumab in patients with extremely high cardiovascular risk].

Aim To study the efficacy and safety of alirocumab in patients with high and very high cardiovascular risk in the Republic of Karelia and to evaluate their compliance with the alirocumab therapy.Materials and methods Study design: observational, noncomparative. The observation group consisted of 9 patients receiving alirocumab (Praluent®) (mean age, 48.6±4.7 years; 7 men). 7 patients had familial hypercholesterolemia of the type diagnosed by DLCN criteria; five patients had MI. Lipid profile, concentrations of transaminases, creatinine, glucose, and lipoprotein a (LP(a)) were measured at 3, 6, 12, and 18 months. Electrocardiography was performed, and the clinical picture (development of acute coronary syndrome, acute cerebrovascular disease, transient ischemic attacks, myocardial revascularization, and cardiovascular death) was evaluated. Efficacy criteria included the absence of these clinical conditions, the proportion of patients who achieved the LDL CS goal, and the decrease in LP(a). Safety was evaluated by clinical and laboratory data, such as levels of transaminases, total bilirubin, creatinine, and blood glucose. The observation lasted for 6 months to 1.5 years.Results LDL CS goals were achieved in 7 (77.8%) patients receiving alirocumab. The mean level of LP(a) decreased from 0.39 to 0.28 g/l; the degree of decrease ranged from 20 to 33 %. No cases of IHD instability (acute coronary syndrome) or new cases of acute cerebrovascular disease and transient ischemic attacks were observed. None of the patients had to stop the alirocumab treatment; adverse effects, including local ones, were not observed.Conclusion LDL CS goals were achieved in 7 (77.8%) patients. The level of LP(a) decreased by 20-33% in patients receiving the PCSK9 inhibitor. In real-life clinical practice, the alirocumab treatment was characterized with high compliance and good tolerability without side effects, including local ones.

Effect of Sulfated Polysaccharides from Marine Hydrobionts on Humoral Immune Response to Ovalbumin in Mice.

Adjuvant activity of fucoidans in experimental vaccine compositions with ovalbumin was studied on a mouse model. Compositions with sulfated polysaccharides from brown alga Fucus evanescens (native fucoidan in combination with polyphenols, and a product of fucoidan enzymatic hydrolysis) induced multiple productions of antigen-specific antibodies - total IgG, its isotypes IgG1 and, especially, IgG2a, in comparison with an individual ovalbumin. The adjuvant effect of native and structurally modified fucoidans is slightly inferior to that of the traditional licensed aluminum hydroxide adjuvant. The results indicate the prospects of using sulfated polysaccharides from F. evanescens as adjuvants in vaccines.

Energy Metabolism in Cellular Regenerative Processes: Focus on PPARα.

Reduced expression of the key regulator of cardiac metabolism, transcription factor PPARα, in surgical samples of the auricles from patients with coronary heart disease and heart failure was detected by real-time quantitative PCR. These changes indicate reduced activity of this factor and a shift of energy metabolism from oxidative phosphorylation to glycolysis typical of dedifferentiated cells. Electron microscopy revealed dedifferentiated cardiomyocytes with disassembled contractile apparatus and disorganized sarcomeres. In the examined specimens from patients with heart failure, severe myocardial fibrosis was revealed.

Markers of Systemic Inflammation in Experimental Dyslipidemia Induced by P-407: Modulation with Fucoidan from Brown Alga Fucus evanescens.

The effect of sulfated polysaccharide from brown alga Fucus evanescens (fucoidan) administered via different routes (peroral and parenteral) on the dynamic of some lipid metabolism parameters and markers of systemic inflammation in mice with experimental dyslipidemia induced by prolonged administration of poloxamer P-407. It was found that fucoidan corrected the main parameters of lipid metabolism, reduced the level of endothelial dysfunction marker endothelin-1 and proinflammatory cytokines TNFα, IFNγ in blood serum in animals with experimental dyslipidemia. These findings open prospects for using fucoidan in the complex treatment of metabolic disorders and atherosclerotic inflammation.

[Lipid Lowering Therapy with Statins in Patients with Heterozygous Familial Hypercholesterolemia].

AIM: to analyze adherence of FH patients with familial hypercholesterolemia (FH) to the statin therapy and reveal factors, which influence it; to assess the degree of target level of low-density lipoprotein cholesterol (LDLCH) achievement by FH patients on statin therapy. Materials and methods. We included in this study 203 FH patients aged >18 years (mean age 50.0±1.1 years, 82 men). Definite FH was diagnosed in 96 persons, in the other patients FH was considered possible. For evaluating the adherence to therapy with statins we used the Morisky-Green questionnaire. Results. Among patients with definite FH 57 % were adherent to lipid-lowering therapy, 16 % were partially adherent, and 27 % - not adherent. Target LDLCH levels were achieved in 22.6 % and 12.5 % of patients with definite and possible FH, respectively. Smoking and gender were not associated with adherence to statin therapy. Factors associated with higher adherence were age (p=0.000003), arterial hypertension (odds ratio [OR] 1.90, 95 % confidence interval [CI] 1.02 to 3.55], p=0.044), ischemic heart disease (IHD) (OR=2.99, 95 %CI 1.50 to 5.97, p=0.002), history of myocardial infarction (MI) (OR 5.26, 95 %CI 2.03 to 13.60, p=0.0006), history of myocardial revascularization (OR 20.3, 95 %CI 2.64 to 156.11, p=0.004) and the fact of achieving target LDLCH level (OR 19.93, 95 %CI 7.03 to 56.50, p<0.0001). The main reason for the refuse from statin therapy in 87 % of patients was fear of side effects. Main reasons for stopping of ongoing therapy were: myalgia, an increase in transaminases, skin rashes, and high cost in 12, 35, 12, and 6 % of patients, respectively. The decision to withdraw therapy with statins was made by 29 % of patients by themselves. CONCLUSION: In this study 57 % of patients with definite FH were adherent to statin therapy. Factors associated with increased adherence were age, hypertension, IHD, history of MI, history of myocardial revascularization, achievement of target LDLCH level. Target LDLCH levels were achieved by 22.6 and 12.5 %% of patients with definite and possible FH, respectively.

[Adjuvants of influenza vaccines: new possibilities of using sulphated polysaccharides from marine brown algae.]

The review article presents the characteristics of the main adjuvant groups (mineral salts of aluminum, synthetic squalenebased adjuvants - MF59 and AS03, CpG-oligodeoxynucleotides, virosomes, polyoxidonium, sovidone) included in the licensed influenza vaccine. The main mechanisms of adjuvant action, advantages and disadvantages of these adjuvants are shown. The vaccines adjuvants in the phase of experimental studies and clinical trials (ISCOMs, Advax™, chitosan) are described too. Particular attention is paid to sulfated polysaccharides (fucoidans) from marine brown algae as vaccine adjuvants. Numerous results of their application in compositions of experimental vaccines are presented. The prospects of sulfated polysaccharides using in the design of influenza vaccines are estimated. These prospects are determined by high biocompatibility, low toxicity and good tolerance of the human body to fucoidans, as well as mechanisms of their adjuvant activity. Sulfated polysaccharides are agonists of toll-like receptors of innate immunity cells and powerful inducers of the cellular and humoral immune response, which is important for the development of influenza vaccines. The review is based on the information presented in the bibliographic and abstract databases of scientific publications, search engines and publishers: RSCI, Web of Science, Scopus, MEDLINE, Google Scholar, PubMed, Springer Nature, Elsevier and others.