Vol 90, No 4 (2018)


Pharmacotherapy of resistant arterial hypertension

Shepeleva N.E., Rodionov A.V., Fomin V.V.


Pharmacotherapy of resistant arterial hypertension represents a serious problem, because today there are no clear algorithms of action in this clinical situation. The review discusses the key works in which the authors propose a solution to this problem. The variants of a differentiated approach to treatment based on hemodynamic type, plasma renin activity, as well as a number of empirical strategies, including the predominant use of mineralocorticoid receptor antagonists, are discussed.
Terapevticheskii arkhiv. 2018;90(4):4-7
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Is it necessary to use capsular endoscopy to diagnose celiac disease?

Parfenov A.I., Akopova A.O., Shcherbakov P.L., Mikheeva O.M., Gudkova R.B.


Aim. To clarify the indications for capsular endoscopy (CE) in patients with celiac disease. Materials and methods. The study included 10 patients with celiac disease (6 women, 4 men) aged 22 to 69 years. The median age was 42.4±17.5 years. The diagnosis of celiac disease established on the basis of histological examination of the mucous membrane (MM) of the duodenum and detection of antibodies to diaminononane peptide gliadin and to tissue transglutaminase. In three patients celiac disease was diagnosed for the first time, in others - in terms of 3 months to 2 years. CE was performed using a Given Imaging systems (Yokneam, Israel), Olympus (Japan), the obtained data were analyzed using Rapidr® Reade (version 7.0). The results of the endoscopy were compared with the data of 78 patients examined by us, in which the indicators conformed to the normal CE criteria. Results. All patients with celiac disease showed characteristic endoscopic markers of atrophy from the small intestine: scallop, nodularity, decrease in height and number of folds. Paid attention to the mosaic of defeat in the form of "atrophy fields" against a background of slightly modified MM. Erosive-ulcerative lesions of the small intestine were found in 4 patients. Conclusion. Indications for the appointment of CE in patients with celiac disease is the lack of response to treatment, which is based on strict adherence to gluten-free diet, the assumption of erosive and ulcerative lesions MM of the small intestine and refractory form of the disease. CE makes it possible to establish the extent of atrophy from the small intestine, which allows you to use it to evaluate the effectiveness of treatment.
Terapevticheskii arkhiv. 2018;90(4):8-11
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Frequency of detection of some markers of endothelial dysfunction in patients with inflammatory bowel diseases

Babayeva G.H., Babayev Z.M.


Aim. The purpose of our study was to determine the frequency of detection of some markers of endothelial dysfunction in patients with inflammatory bowel disease (IBD). Materials and methods. The study was conducted on the basis of the Therapy Department of of A. Aliyev Azerbaijan State Advanced Training Institute for Doctors, the Department of Inflammatory Bowel Diseases "MedEra Hospital" and "Memorial Klinika" between March 2015 and September 2017. In patients with ulcerative colitis and Crohn's disease, homocysteine (Axis-Shield, IFA method) and hs-CRP (Biomerica, IFA method) in the blood, albumin (MicralTest, Roche Diagnostics) in urine were determined. The study included 87 patients with inflammatory bowel diseases (the diagnosis was confirmed on the basis of ECCO recommendations) in whom there was no history of nephro -, cerebro - and cardiovascular pathology in the anamnesis. Results and discussion. Of the 48 patients with Crohn's disease, 45 homocysteine levels were elevated and comprised 12.9-48.7 μmol/L in the 15-60 year old; and in the group of patients older than 60 years fluctuated within 16.5-34.6 μmol/L. Out of 48 patients with Crohn's disease, 47 showed both albuminuria (micro - and macroalbuminuria) and was 22.8-98.5 mg/L. Of the 48 patients with Crohn's disease, 31 had an increase in hs-CRP between 4.3-47.1 mg/L; of them in 14 patients less than 10 mg/L, in 8 patients from 10.1-20.0 mg/L, and in 9 patients it ranged more than 20.0 mg/L. Of the 39 patients with ulcerative colitis, the level of homocysteine in 33 was elevated and amounted to 13.4-48.7 μmol/L in the 17-40 year old group; in the 41-59 year old group, 14.9-31.3 μmol/L; and in the group of patients older than 60 years fluctuated within the range of 16.9-41.7 μmol/L. Out of 39 patients with ulcerative colitis, 24 had albuminuria (both micro - and macroalbuminuria) and was 21.9-146.5 mg/L. Of 39 patients with ulcerative colitis in 36, an increase in hs-CRP was observed in the range 3.5-118.7 mg/L; of them in 17 patients less than 10 mg/L, in 6 patients from 10.1-20.0 mg/L, in 13 patients it ranged more than 20.0 mg/L. Conclusion. The frequency of detection of some markers of endothelial dysfunction in Crohn's disease was on the average 85.3%: for homocysteine 93.7%; for hs-CRP 64.5%; for albuminuria 97.9%, and for ulcerative colitis averaged 79.4%: for homocysteine, 84.6%; for hs-CRP 92.3%; for albuminuria 61.5%. Because of the high incidence of these markers, patients with inflammatory bowel diseases need a multi-disciplinary approach.
Terapevticheskii arkhiv. 2018;90(4):12-16
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The prevalence of Helicobacter pylori infection among urban population

Zhestkova T.V., Butov M.A., Papkov S.V.


Aim. Determination of the prevalence of Helicobacter pylori infection (H. pylori) among the urban population. Materials and methods. 655 people (638 adults and 17 children) were examined using the immunoassay method of quantitative detection of IgG class antibodies. The results and discussion. High infection of adult residents of Ryazan H. pylori - 64,4% is established. The greatest prevalence of H. pylori infection was observed in individuals 41 to 80 years of age (66,9%). Discovered gender differences in the prevalence of H. pylori infection in persons older than 40 years. H. pylori infection in males aged 41-80 was 76.3%, compared with 65.3% in females (p=0.02). In children 4-15 years, the proportion of persons with positive serological test anti-H. pylori IgG reached 23.5%. All H. pylori infected children were over 9 years of age. 90% of adults with H. pylori infection was detected, isolated or concomitant gastrointestinal symptoms of indigestion. More often, H. pylori infection was associated with abdominal pain - 48.3% (p=0.005) and heartburn - 27% (p=0.04). Conclusion. The data obtained indicate a high proportion of H. pylori infection in the adult population in Ryazan - 64,4%. The incidence of detection of anti-H. pylori IgG in the population maximum from individuals 41 to 80 years of age (66,9%).
Terapevticheskii arkhiv. 2018;90(4):17-20
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Differences between passport and biological (actual) age in the population of Russian patients suffering from arterial hypertension (analysis of the «Hyperion» register)

Arutyunov A.G., Nozdrin A.V., Shavgulidze K.B., Tokmin D.S., Osadchiy I.V.


The age of the patient is the most important factor determining the high risk of cardiovascular diseases. The subject of modern research was the study of the clinical role of the patient's biological age and its difference from passport age. The aim of the study was to analyze the severity of the difference in these values in real clinical practice in patients suffering from arterial hypertension (AH) on the basis of an open multicenter register to monitor the effectiveness of therapy in patients with hypertension "HYPERION", conducted by the Eurasian Association of Therapists with the support of the company "Gedeon Richter" (Hungary). Materials and methods. The study was carried out within the open multi-center register "HYPERION". The final analysis of the register included 1441 patients, including 638 men (44%), 803 women (56%) aged 24 to 90 years. All patients were observed in primary health care (55 centers in 47 cities of Russia) for hypertension, received at least two hypotensive drugs. According to the data on 1424 patients using the qrisk-2 scale of 2017 modification, the biological age was calculated. Results and discussion. The absolute majority of patients (83,7%) had biological age >70 years, while the passport age of the absolute majority (65,3%) is in the range ≥50, but ≤69 years. Median difference between biological and passport age was 15 years. On average, in men suffering from hypertension, the biological age exceeded the passport age by 17.6 years, and in women - by 13.4 years. The difference between the value of biological and passport age and the level of systolic pressure in all age groups had a direct correlation. At systolic blood pressure >181 mm Hg. the difference between biological and passport age was the maximum, reaching the highest values in the youngest age group (30-39 years). Conclusion. Analysis of the actual (biological) age should be a mandatory procedure that allows a more complete assessment of the initial therapeutic status of the patient, which is especially important in patients aged 30-50 years. This is necessary not only from the standpoint of changing the current procedure, but also to understand the patient's prognosis.
Terapevticheskii arkhiv. 2018;90(4):21-28
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Features of structural heart remodeling in chronic atrial fibrillation against the background of coronary artery disease with hypertension

Mironchuk N.N., Amineva L.K., Mirsaeva G.K., Yunusova A.S.


Aim. To reveal the peculiarities of structural myocardial remodeling in patients with chronic atrial fibrillation (AF) against the background of chronic ischemic heart disease (CIHD) with arterial hypertension (AH). Materials and methods. Two groups of patients with CIHD with AH were formed: 1st - against the background of chronic AF (n=44) and 2nd - without FP (n=100). Anthropometric, general clinical and echocardiographic data were evaluated. Results and discussion. Left ventricular hypertrophy (LVH) was observed in all patients with FP and in 96% of patients without FP, the groups did not differ in types of LVH (u-test Mann-Whitney p=0.7489). In both groups dominated by concentric hypertrophy: in the 1st group of 22 (50%) and in the 2nd group - 51 (51%), Fisher's exact test p=1,0. The linear dimensions of both atria were larger in group 1: the ratio of the left atrium/body surface area (BSA) in group 1 was 2.7 [2.2; 3] cm/m2 versus 2.1 [1.8; 2.5] cm/m2 in group 2 (U-test p=0.000004); the attitude of the right atrium / BSA - in the 1st group and 2.9 [2,4; 3,2] cm/m2 vs 2.3 [2,2; 2,6] cm/m2 in the 2nd group (U-test p<0.0000001). The level of calculated systolic pulmonary artery pressure in patients with AF was higher than in control: 38 [32; 41] mm Hg. vs. 27 [24; 31] mm Hg. art. respectively (U-test p<0.0000001). A more severe stage of chronic heart failure (CHF) was diagnosed in patients of the 1st group (U-test p=0.0000001). Conclusion. In patients with combination like hibs and hypertension remodeling affects both the LV and the atrium. In the presence of AF in such patients, structural changes in atria are more significant. AF itself is a predictor of chf and can contribute to the progression of heart failure in patients with CIHD and AH.
Terapevticheskii arkhiv. 2018;90(4):29-34
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Predictors of community-acquired pneumonia in patients with acute decompensated heart failure: the results of the analysis of the hospital sample EPOHA-D-CHF

Polyakov D.S., Fomin I.V., Vaisberg A.R., Valikulova F.Y., Ivanchenko E.Y., Kraiem N.


Community-acquired pneumonia is a significant factor leading to acute decompensated heart failure (ADHF). Each subsequent decompensation of the patient with heart failure leads to decrease in the functional reserve of the myocardium and worsens the life prognosis of this patient. Aim. Identify the most significant predictors of community-acquired pneumonia and their im-pact on the risk of this disease in patients with ADHF. Materials and methods. The analysis of the hospital sample of patients (n=852) with ADHF. In 16.5% of hospitalizations, community-acquired pneumonia was found. Results. The presence of symmetrical rales in the lungs, hepatomegaly, left ventricular failure signs, dilated cardiomyopathy, hypotension are increasing the risk of pneumonia in 3.7 (p<0.001), 1.6 (p=0.02), 1.86 (p=0.005), 1.72 (p=0.002), 2.7 (p=0.003) times. Conclusion. Based on results of a single and multivariate regression analysis, the risk of pneumonia is statistically significant increase in patients with acute left ventricular failure, dilated cardiomyopathy, hypotension, with signs of stagnation in the small and large circulatory circles. Different combinations of these predictors were found in 80% of patients with ADHF, among which in 20% of cases there was a combination of 3-5 factors.
Terapevticheskii arkhiv. 2018;90(4):35-41
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Gender features of comorbidity in patients with coronary artery disease

Sumin A.N., Korok E.V., Shcheglova A.V., Barbarash O.L.


Aim. To study the factors associated with high levels of comorbidity in men and women with coronary artery disease (CAD). Materials and methods. The data analyzed 742 patients who were screened in the clinic of the research Institute CPSS in 2011, before planned operation coronary artery bypass grafting. All patients were divided into 2 groups: group I - men (n=595; 58 [54; 64] years), group II - women (n=147; 63 [57; 69] years). Results and discussion. The analysis showed that the presence of arterial hypertension and atrial fibrillation prevailed in the group of women (p<0.05), and postinfarction cardiosclerosis (PIC) in the group of men (p=0.004). Men mainly observed lighter I and II functional classes (FC) of angina (p=0.057 and p=0.007) and I stage of chronic heart failure (CHS; p<0.001), women, on the contrary, III and IV FC angina (p=0.005 and p=0.050) and stage III CHS (p<0.001). Atherosclerotic lesions of the arteries of the lower extremities (ALE) were significantly more common in men (p=0.022). Diabetes mellitus (DM), thyroid disease, varicose disease and bronchial asthma (BA) prevailed in the group of women (p<0.05), and chronic hepatitis (p=0.079) and urolithiasis in the group of men (p=0.028). Calculation of the level of comorbidity did not show significant intergroup differences (p>0.05). Although the average level of comorbid pathology prevailed in the whole population - 66% among women and 70.4% among men. Independent predictors that increase the level of comorbidity in male group were: the presence of underground experience, PIC in anamnesis, diabetes, chronic lung disease, stenosis of the ALE for more than 50% increase in the level of glucose in the group of women - the presence of the clinic of angina pectoris IV FC, PIC and movements in the history of the ALE stenosis more than 50%, diabetes, peptic ulcer disease, chronic lung disease, ASTHMA, improving glucose levels (p<0.05). Conclusion. According to the analysis, a high level of comorbidity was found in 13.6% of women and 11.6% of men. Factors associated with high levels of comorbidity, both in men and women were: the presence of diabetes, chronic lung disease, PIC, atherosclerosis of the ALE. At the same time only in women the high level of comorbidity was associated with angina IV FC, peptic ulcer disease, BA, and only in men - with the presence of underground experience. Detection of comorbid pathology in patients with IHD taking into account gender features is advisable for the implementation of patient-oriented approaches in daily clinical work.
Terapevticheskii arkhiv. 2018;90(4):42-49
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Certolizumab pegol in treatment of Crohn's disease with perianal lesions

Khalif I.L., Nanaeva B.A., Shapina M.V., Vardanyan A.V.


Aim. To assess the effectiveness of conservative treatment of Crohn's disease (CD) with perianal lesions. Materials and methods. The study included 20 patients with CD with perianal fistulae. Prior to the start of conservative therapy, 7 patients underwent fistulae drainage with setton placement. During the study, all patients received therapy with certolizumab pegol (CP) for a year. At the time of treatment initiation and after 12 months, the CD activity index, the quality of life according to IBDQ questionnaires and the perianal Crohn's disease activity index (PCDAI) were assessed. Results. After a year of CP therapy, clinical remission was achieved in 8 (40%) patients, endoscopic remission in 7 (35%) patients, fistula closure in 6 (30%) patients. There was also a decrease in the PCDAI with the average score 3.6 points compared to 9.3 points (p˂0.05) prior to the treatment. An improvement in the quality of life of patients was also established, the average quality of life index was 182,2 points compared to 156,0 points (p˂0.05) prior to the treatment. Conclusion. This study showed that CP therapy is effective in treatment of CD with perianal lesions.
Terapevticheskii arkhiv. 2018;90(4):50-54
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Modern view on the place of riociguat in the treatment of pulmonary hypertension

Valieva Z.S., Taran I.N., Martynyuk T.V., Chazova I.Y.


Current research is aimed at studying the fundamental therapeutic targets and discovering new drugs acting on previously set targets. Until recently, the only therapeutic strategy to influence the molecular pathway of nitric oxide (NO) - soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) was the use of phosphodiesterase type 5 inhibitors (PDE-5 inhibitors), such as sildenafil. In September 2014, the first member of sGC stimulators riociguat was licensed in Russia. In the paper, the results of 5 multicenter studies (CHEST-1 and PATENT-1, CHEST-2 and PATENT-2, RESPITE), which reflect the effectiveness and safety of mono - and combination therapy with riociguat in patients suffer from some forms of pulmonary arterial hypertension, and patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTPH), as well as the possibility of optimizing therapy in patients with PAH using iPDE-5 -> riociguat switching was reviewed. It also provides information on the recently launched international registries EXPERT CTEPH; new REPLACE study was announced.
Terapevticheskii arkhiv. 2018;90(4):55-59
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Computed tomography diagnosis of primary hyperparathyroidism

Buryakina S.A., Tarbaeva N.V., Volevodz N.N., Kovalevich L.D., Karmazanovskiy G.G., Dedov I.I.


The article presents data on modern approaches to the diagnosis of various manifestations of hyperparathyroidism according to multispiral computed tomography, which do not require morphological verification and ensure the correctness of the diagnostic process. The radiological picture and differential diagnostics of changes from parathyroid glands and bone structures at hyperparathyroidism are described in detail.
Terapevticheskii arkhiv. 2018;90(4):60-66
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Correction of anxiety disorders: focus on a comorbid patient

Shavlovskaya O.A., Kuznetsov S.L.


The exact cause of the development of anxiety disorders (AD) in present time has not been fully established and is a subject of debate in many countries. Interest in studying the mechanisms of action of proteins of S100 group, in particular, neurospecific protein S100b, is caused by its participation in processes of integrative activity of brain/neuron and development of diseases of nervous system. The functions of S100 proteins determine their influence on synaptic plasticity and participation in the regulation of stress-realizing and stress-limiting systems, the imbalance of which (primarily, the insufficiency of the GABA-ergic system) is the neurobiological basis of the majority of anxiety-depressive pathologies. Preparations regulating the activity of S100 protein have a distinct clinical anti-anxiety effect and additionally contribute to the restoration of neuronal plasticity processes.
Terapevticheskii arkhiv. 2018;90(4):67-71
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New horizons for the use of the second generation of endothelin receptor antagonist macitentan in patients with pulmonary hypertension

Martynyuk T.V., Nakonechnikov S.N., Chazova I.Y.


Since 2015, macitentan, the new oral dual endothelin receptors antagonist (ERA), has been successfully introduced into clinical practice in the Russian Federation for the treatment of pulmonary arterial hypertension (PAH) patients. It has improved physicochemical properties, which provides tissue specificity. Among ERA and other drugs of specific therapy, macitentan is the only one with indication-prevention of PAH progression. In the randomized, placebo-controlled study SERAPHIN in 742 PAH patients aged >12 years, macitentan 10 mg compared with placebo reduced the risk of morbidity and mortality by 45%. By month 6, macitentan with favorable tolerability profile provided a significant increase in the 6-minute walk test distance, the improvement of the functional class (FC) and hemodynamic parameters - pulmonary vascular resistance (PVR) and cardiac index. Macitentan significantly reduced the need for hospitalization for all reasons, including associated with PAH worsening. This review presents a modern view on the possibility of using macitentan in the clinical practice. It is shown that the drug is an important choice among ERA for the treatment of PAH patients. In the study MERIT-1 macitentan significantly improved PVR (geometric mean ratio 0.84, 95% CI 0.70-0,99, p=0.041) in inoperable CTEPH patients. The evidence base for the macitantan use in various PAH subgroups, including portopulmonary hypertension, in children as well as beyond group 1 - CTEPH, left heart diseases - is supplementing with the new data, which will expand the possibilities of its clinical use.
Terapevticheskii arkhiv. 2018;90(4):72-80
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Personalized strategies in reproductive medicine for patients with endocrine disorders

Grigoryan O.R., Andreeva E.N., Dedov I.I.


Endocrine Medical Research center (EMRC) of the Ministry of health of Russia is unique clinical center, that have no analogs in the world. All forms of endocrine disorders may be diagnosed and treated here by implication of innovative methods. Institute of reproductive medicine of EMRC was open on 2017, director of this institute - MD, PhD E.N. Andreeva. Staff of this institute include highly experienced investigators and physicians. One of the most ambitious projects of the institute is development of prevention, diagnostic and treatment algorithm for patients with infertility of endocrine origin. For these purposes large prospective clinical trial (5000 patients) will be conducted with implementation of most modern genetic, laboratory and instrumental diagnostic methods. Results of this trial will allow diagnose, treat and prevent reproductive pathology in patients with endocrine diseases.
Terapevticheskii arkhiv. 2018;90(4):81-84
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A new look at dietary fibers in metabolic syndrome

Onuchina E.V.


Metabolic syndrome (MS) is a cluster of factors associated with high risk of initiation of cardiovascular diseases, of diabetes of the 2nd type, total and cardiovascular mortality. The prevalence of MS in the general population averages 10-25%, varying depending on the region of the world from 3 to 71.7%. Two recent large meta-analysis found an inverse relationship between risk of MS and consumption of dietary fiber. Great prospects have dietary fiber for the maintenance of individual MS components. The review of modern literature presents cohort studies and randomized controlled trials, including generalized meta-analyses and systematic reviews, indicating the impact of soluble high-viscosity gel-forming, non-fermentable dietary fiber-psyllium on the weight of visceral fat, achieving metabolic control, including correction of disorders of carbohydrate, lipid, purine metabolism and regulation of blood pressure.
Terapevticheskii arkhiv. 2018;90(4):85-90
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Multiple calcifying aponeurotic fibroma: case report and review of the literature

Chaltsev B.D., Vasilyev V.I., Pavlovskaya A.I., Palshina S.G., Nikonorova N.O.


We describe the first case of diagnosis of generalized calcifying aponeurotic fibroma in 52 year-old man receiving long-term therapy for seronegative rheumatoid arthritis with rheumatoid nodules. The prevalence of lesions (presence of multiple subcutaneous nodules in the aponeuroses and fascia of the head, neck, trunk, upper and lower extremities with massive deposition of calcium salts), and a combination with monoclonal secretion (IgGκ serum, BJκ in the urine), raised inflammation markers, suggest that this case of the disease is unique, so both in domestic and foreign literature contains no description of this unusual course of this type of mesenchymal tumor. We have shown that subcutaneous nodules biopsy followed by morphological and immunohistochemical study is required in the diagnosis of the disease. We have given the literature data on the clinical manifestations, methods of diagnosis and differential diagnosis of this disease with a variety of pathologies, accompanied by the development of multiple calcification.
Terapevticheskii arkhiv. 2018;90(4):91-95
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Three cases of late syphilitic hepatitis

Loseva O.K., Dergacheva I.A., Zalevskaya O.V., Chernysheva N.V., Zhukovsky R.O.


The article presents literature data for the last 10 years on specific liver damage. There are three own clinical cases of syphilitic hepatitis, one of them - with a lethal outcome. Attention is drawn to the importance of early diagnosis of syphilitic hepatitis. The main criteria for the diagnosis of this pathology.
Terapevticheskii arkhiv. 2018;90(4):96-99
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The role of the mLDL-induced activation of the complement system classical pathway and C3 expression stimulation in atherosclerosis

Drapkina O.M., Gegenava B.B., Fomin V.V.


The role of modified low density lipoprotein in the activation of the classical pathway of the complement system and increasing expression C3 gene in human macrophages is described, role of these processes on the progression of atherosclerotic vascular lesions is considering.
Terapevticheskii arkhiv. 2018;90(4):100-104
pages 100-104 views

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