Vol 75, No 6 (2020)


Modulation of instinal microbiom in the formation and progression of ulterative colitis.

Bikbavova G.R., Livzan M.A.


In recent decades, an increase in the incidence of ulcerative colitis has been observed throughout the world. The purpose of this review is to generalize the available information on the influence of environmental factors and intestinal microbiome on the occurrence and development of ulcerative colitis, the role of bacteria metabolism products in the pathogenesis of the disease. Studied literature, we came to the conclusion that lifestyle in the era of post-industrial society has a significant impact on the microbial composition of the intestine and leads to changes in its diversity in patients suffering from ulcerative colitis. The changes include a decrease in the number of residential flora with anti-inflammatory activity, which synthesize short-chain fatty acids, and an increase in the number of potentially pathogenic and pathogenic microorganisms. Within the phylums Firmicutes and Proteobacteria, the proportional ratio changes. The combination of aggression factors (deterioration of the intestinal microbiome composition, the presence of aggressive intestinal metabolites) leads to intestinal mucosa permeability disfunction, impairing its barrier function. Food and bacterial agents can penetrate deeper layers of the intestinal wall through mucosal defects, which then stimulate the development of inflammatory and immune responses.

Annals of the Russian academy of medical sciences. 2020;75(6):577-584
pages 577-584 views


The role of lipids in the signaling mechanisms of toll-like receptors

Kytikovа O.Y., Novgorodtseva T.P., Denisenko Y.K., Antonyuk M.V., Gvozdenko T.A.


Toll-like receptors (TLRs) are important players in innate and adaptive immune responses involved in the initiation of the inflammatory process in response to the stimulating influence of endogenous (аllarmine) and exogenous ligands (pathogens viruses, bacteria, fungi). It has now become apparent that not only viral and bacterial infections but non-infectious inflammatory diseases are accompanied by the activation of inflammatory response systems and the development of chronic inflammation associated with disorders in the regulation of the TLRs system. In this regard, the ligand-independent activation of TLRs, which occurs with the participation of lipids, is actively studied. Their signalling functions of TLRs implemented in unique microdomains does membrane lipid rafts that coordinate many cellular processes. The ability to activate TLRs has been found for saturated fatty acids (SFAs), both exogenous and endogenous. On the other hand, TLRs can be inhibited by omega-3 polyunsaturated fatty acids (PUFAs), which can block the inflammatory process. The activation of TLRs triggers a signal cascade that induces the production of reactive oxygen and nitrogen species. The development of oxidative stress is accompanied by the formation of oxidized forms of phospholipids (Ox-PLs), which also induce the development of chronic inflammation. At the same time, Ox-PLs is characterized not only by pro-inflammatory but also anti-inflammatory activity, which necessitates in-depth studies of their role in the implementation of these processes. This review article discusses the mechanisms by which SFAs, PUFAs, and Ox-PLs modulate TLRs activation in lipid rafts. Research into the details of these mechanisms will contribute to the development of a strategy to reduce the risk of chronic diseases caused by inflammatory reactions mediated by TLRs.

Annals of the Russian academy of medical sciences. 2020;75(6):585-593
pages 585-593 views


Combination of Arrhythmogenic Right Ventricular Dysplasia with Left Ventricular Non-Compaction as a Special Form of Cardiomyopathy: Clinic, Diagnostics, Genetic, Natural Course

Lutokhina Y.A., Blagova O.V., Shestak A.G., Polyak M.Е., Bukaeva A.A., Zaklyazminskaya E.V., Varionchik N.V., Sedov V.P., Kogan E.A., Alexandrova S.А., Nedostup A.V.


Background. A few cases of combination of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) with left ventricular noncompaction (LVNC) have been described. Aims — to study the genetics, diagnostical features and clinical course of the combination of ARVC with LVNC. Methods. 58 patients with ARVC diagnosis (26 men; mean age 39.1 ± 14.2 years; mean follow-up period — 21.5 [6; 60] months) and 125 patients with LVNC (74 men; mean age 46.4 ± 15.1 years; mean follow-up period — 14 [3; 40] months). All patients underwent electrocardiogram (ECG), echocardiography, 24-h ECG monitoring. Heart MRI was performed in 53 (91.4%) patients with ARVC and 60 (48%) with LVNC, heart CT — in 18 (31%) patients with ARVC and 89 (71.2%) with LVNC. For all patients with combination of ARVC and LVNC DNA-diagnostic was performed using both ARVC (PKP2, DSG2, DSP, DSC2, JUP, TMEM43, TGFB3, PLN, LMNA, DES, CTTNA3, EMD, SCN5A, LDB3, CRYAB, FLNC) and LVNC (MYH7, MYBPC3, TAZ, TPM1, LDB3, MYL2, MYL3, ACTC1, TNNT2, TNI3) gene panels. Results. Combination of ARVC and LVNC was found in 9 patients (15.5% of patients form ARVC cohort and 7.2% from LVNC cohort). These patients were distinguished from patients with isolated ARVC or LVNC by aggressive ventricular arrhythmias (frequent premature ventricular beats, sustained ventricular tachycardia, significantly worse antiarrhythmic therapy effect, appropriate shocks of implanted cardioverter-defibrillators (ICD) in all patients with ICD). Patients with combination of ARVC + LVNC were also distinguished from patients with isolated LVNC by the dilatation of RV, low QRS voltage on ECG, presence of AV block, absence of signs of LV hypertrophy on ECG. LV dilatation with reduction of its ejection fraction distinguished patients with mixed cardiomyopathy from patients with isolated ARVC. Potentially pathogenic variants (IV–V classes of pathogenicity) and variants of unclear clinical significance (III class of pathogenicity) were found in both desmosomal and non-desmosomal genes in 78% of patients, including 3 (33%) — in DSP gene. Conclusions. The combination of ARVC and LVNC can be caused by mutations in both desmosomal and non-desmosomal genes and has typical features: aggressive, resistant ventricular rhythm abnormalities leading to appropriate ICD shocks and a high risk of sudden cardiac death.

Annals of the Russian academy of medical sciences. 2020;75(6):594-604
pages 594-604 views


Metabolic disorders in the pathogenesis of various causes of dizziness and instability

Bedenko A.S., Antonenko L.М., Barinov A.N.


Dizziness and instability are topical problem in the neurological practice. This health condition invades up to thirty percent of the whole population. However, pathogenic factors of development and tendency to chronic process of these nosological conditions are still poorly researched. The investigation of new pathogenic factors, including metabolic factors, is proceeding. The greatest amount of research was collected for benign paroxysmal positional vertigo (BPPV). The hypothesis of coincidence between BPPV, vitamin D deficiency and osteoporosis was created in 2003. However, the results are controversial. The complex of perfomed investigations let suspect vitamin D deficiency as biomarker of osteoporosis/osteopenia. But some other research works failed to support this conclusion. In some investigations the vitamin D deficiency as factor of recurrence of BPPV was discussed. The new hypothesis was correlation between otoneurological disorders and vitamin D deficiemcy due to it’s immunomodulation ability was proposed. Considerable part of the article deals with problem of endothelial dysfunction. The data about correlation between oxidative stress and BPPV was published, as far as the data about impact of hypehomocysteinemia to retardation of compensation for vestibular neuritis.

Annals of the Russian academy of medical sciences. 2020;75(6):605-608
pages 605-608 views


Role of cytokines in the pathogenesis of glaucoma

Rakhmanov V.V., Sokolov D.I., Selkov S.A., Astakhov Y.S., Astakhov S.Y.


Glaucoma is one of the leading causes of irreversible blindness worldwide and belongs to age-related diseases. However, its pathogenesis is not fully understood. Primary open-angle glaucoma (POAG), pseudoexfoliative (PE) glaucoma are the most common forms of glaucoma. Increased intraocular pressure (IOP) is one of the main risk factors for glaucoma progression. The trabecular meshwork participates in regulating and maintaining a constant level of IOP throughout life. Impairment of intercellular interactions, development of cellular dysfunction and the associated imbalance of pro- and anti-inflammatory cytokines and growth factors underlie the development of most age-related diseases. The role of chronic inflammation, changes in innate and acquired immunity in the development of glaucoma is currently being discussed. Aqueous humor (AH) contains cytokines and growth factors, which are the most important link in the processes of intercellular interaction and are produced by cells of various structures of the eye both in physiological and in pathological conditions. The study of the spectrum, levels, and ratio of different mediator molecules in patients with glaucoma has not yet had a systematic approach. The data obtained are contradictory, which is due to the use of various biological fluids (plasma, AH, tear), determination methods, and the variability of the studied groups of patients. The purpose of this review was to systematize the accumulated knowledge about the role of cytokines and immune system cells in the pathogenesis of glaucoma. Research in this direction will not only reveal new predictive biomarkers, but also develop new approaches in glaucoma therapy.

Annals of the Russian academy of medical sciences. 2020;75(6):609-616
pages 609-616 views


The Rating System of Urodynamics Upper Urinary Tract in Children under Three Years Old with Congenital Hydronephrosis

Rostovskaya V.V., Кhvatynets N.А., Kuzovleva G.I., Matyushina К.М.


Background. One of the main reasons for the incorrect differentiation of obstructive and non-obstructive disorders of the upper urinary tract (UUT) is age-related morphofunctional immaturity of the kidney and its structures in children of the first three years of life. Aims — to investigate to determine the peculiarities of urodynamic disorders of the UUT in infants with congenital hydronephrosis using diuretic pyeloehography (DРG) method. Methods. There were studied DPG data of 55 patients aged 3–36 months with unilateral hydronephrosis of I–III grades SFU, which were divided into groups in accordance with the variant of violation of the urodynamics of the UUT (obstructive, obstructive-hypertensive and disadaptive). The variants established according to the parameters of the DPG (transient coefficient PUJ (Kpus), the coefficients of postfurosemide adaptation (Ka) and the efficiency of emptying (Ko) pelvis). The obtained data are compared with the conclusions of morphometric studies of the operated 20 children with ureteropelvic junction obstruction (UPJO). Results. The obstructive-hypertensive variant was determined in 18 patients, obstructive — in 20, and disadaptive — in 17. The severity of pelvic dysfunction (according to Ka and Ko) did not correlated to the grade of UPJO (according Kpus) in most cases. Intergroup and intragroup variability in the values of the DРG coefficients is confirmed by the results of PUJ and pelvis morphometry. The correlation between hystological modification in the pelvis and DPG parameters was revealed. Obtained data allowed to introduce a new indicator — urodynamic indicator of quantitative assessment of functional insufficiency of the UUT. And the score gradation of each DРG coefficient (from 0 to 4 points) in accordance with deviation from the reference values was developed. The total indicator functional insufficiency is expressed by the sum of points (SP) for each coefficient (Ka, Ko, Kpus). When SP is less than 3 points — light, 4–6 — moderate, 7–9 — expressed and 10–12 — severe grade of violation of urodynamics. The severity of dysfunctions of the UUT in 88% of children (n = 15) with a disadaptive variant corresponded to light degree, in 75% of patients (n = 14) with an obstructive-hypertensive variant — expressed (50%) and severe (25%) grades. Moderate degree of dysfunction revealed in 65% of patients (n = 13) with an obstructive variant. Conclusion. The severity of urodynamic dysfunction of the UUT in this age group can be determined by the score gradation of the DPG parameters which reflects the functionality of the pelvis/PUJ and the grade of their violation adaptive reactions in response to diuretic.

Annals of the Russian academy of medical sciences. 2020;75(6):617-630
pages 617-630 views

Remodeling of the Heart of the Premature Child

Kovtun O.P., Tsyvian P.B., Markova T.V., Chumarnaya T.V.


Epidemiological studies consistently have suggested an association between low birth weight and increased rate of cardiovascular morbidity and mortality in adult life. Preterm birth, as one of the leading causes of the low birth weight, is associated with cardiovascular remodeling which consists of changes in heart chambers geometry and contraction-relaxation mode, ventricular hypertrophy, arterial wall structure and density changes. Several types of preterm birth are discussed: prematurity, associated with placental insufficiency and fetal growth restriction, preterm leaking of amniotic fluid, and twin pregnancy. DNA methylation process under the influence of epigenetic factors of the intrauterine and early postnatal development is suggested as a one of the main mechanism of cardiovascular remodeling in preterm infants. The other mechanisms of cardiovascular remodeling are discussed in terms of the modern intrauterine programming concept. The early diagnostics and prevention of cardiovascular diseases in preterm born children are discussed. The treatment during prenatal and early postnatal periods as well as prevention of the remodeling causes could diminish and even reverse the development of the negative cardiovascular events and diseases in later life according to the so called concept of “one thousand days opportunities window”.

Annals of the Russian academy of medical sciences. 2020;75(6):631-637
pages 631-637 views


The role of homeostatic proliferation and SNP mutations in MHC genes in the development of rheumatoid arthritis

Shevyrev D.V., Kozlov V.A.


Great efforts have been made to study the etiology and pathogenesis of rheumatoid arthritis in the last few decades, but this issue remains widely unknown. In this review, we suggest a hypothesis according to which the development of rheumatoid arthritis is associated with a genetically determined enhancement of self-antigens presentation and decrease in TCR repertoire diversity due to homeostatic proliferation (HP). We suppose that qualitative changes in the TCR landscape of effector and regulatory T-cells populations lead to immune disequilibrium. I.e. HP results in the condition when self-reactive T-cell clones appear to which no specific T-regulatory cells exist. If such self-reactive clones have TCR specific to modified auto-antigens, which presentation increased due to SNP mutations in MHC genes, then the adaptive immunity is activated, and rheumatoid arthritis develops. Obviously, therapy based on the deletion of self-reactive T-cells clones involved in the RA process or on the replenishment of Treg clones by CAR-T-cells is the perspective approach of personalized medicine.

Annals of the Russian academy of medical sciences. 2020;75(6):638-646
pages 638-646 views


Diabetes Mellitus and Thyroid Dysfunction, Including Autoimmune Genesis. Mutual Influence of Pathologies

Tkachuk A.V., Mikhina M.S., Ibragimova L.I., Nikonova T.V., Troshina E.A.


Thyroid disease, including autoimmune genesis, and diabetes mellitus are the two most common endocrine diseases in clinical practice. These pathologies have a mutual influence on each other. On the one hand, thyroid hormones are involved in regulation of carbohydrate metabolism: excessive production of thyroid hormones is associated with hyperglycemia, while hypothyroidism has a decreased level of glucose production by the liver. On the other hand, glucose homeostasis disorder affects the functional state of the thyroid gland: dystrophic, sclerotic and atrophic processes are developing in thyroid gland, what is a manifestation of diabetic microangiopathy. This article demonstrates the need to take into account the mutual influence of pathologies for optimal treatment of this conditions.

Annals of the Russian academy of medical sciences. 2020;75(6):647-652
pages 647-652 views

Features of the functional state of the pituitary-ovarian systems in women with polycystic ovary syndrome at different periods of reproductive age

Krusko O.V., Sholokhov L.F., Belenkaya L.V., Rashidova M.A., Danusevich I.N., Nadelyaeva Y.G., Lazareva L.М., Kolesnikova L.I.


Background. PCOS is one of the most common endocrinological pathologies in women of reproductive age, manifested by a wide range of clinical manifestations. There are many unresolved issues related to the pathogenesis, diagnosis and treatment of this pathological condition in different periods of reproductive age. Aim — the objective of the study was to identify the features of the functioning of the pituitary-ovarian system in women with PCOS at different periods of reproductive age. Methods. Study was performed in 2017–2019 at the FSPSI SCFHHRP, and involved women aged 18–45 years. The study groups included women (a group of women with PCOS and a control group) in the follicular phase from 1 to 12 days of the menstrual cycle. As a result of the survey, a group of 44 women with PCOS and a group of 56 healthy women were formed. PCOS was diagnosed according to ESHRE/ASRM criteria (Rotterdam, 2003). Next, subgroups of women in early reproductive age from 35 to 45 years were formed: a group of women with PCOS (n = 29) and a control group (n = 22). And groups of women in late reproductive age from 35 to 45 years were formed: a group of women with PCOS (n = 15) and a control group (n = 34). Conducted: questionnaire survey, general and gynecological examination, ultrasound examination of the pelvic organs, laboratory tests, statistical data analysis. Results. In women with polycystic ovary syndrome of early reproductive age (18–35 years), we detected an increase in the level of testosterone by 2 times, DHEA-S by 1.3 times, 17-OH-progesterone by 2 times, sex steroid-binding globulin by 1.4 times, in comparison with control group. The ratio of luteinizing hormone to follicle-stimulating hormone increased by 52%. In women with polycystic ovary syndrome of late reproductive age (35–45 years), we detected an increase in the level of testosterone by 1.5 times, 17-OH-progesterone by 1.9 times, luteinizing hormone by 1.4 times, sex steroid-binding globulin by 1.6 times, in comparison with control group, without any significant differences in DHEA-S. At the same time, the ratio of luteinizing hormone to follicle-stimulating hormone increased by 60%. Conclusion. The hormonal profile of women with PCOS of early and late reproductive period is characterized by series of age-related changes in the pituitary-ovarian system, which should be taken into account in preventive and therapeutic measures.

Annals of the Russian academy of medical sciences. 2020;75(6):653-660
pages 653-660 views

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