The review is devoted to the influence of central sleep apnea and Cheyne-Stokes breathing on the prognosis of patients with chronic heart failure. The connection between sleep breathing disorders and an increased risk of ventricular arrhythmias and the mechanisms of these interactions are discussed, and options for approaches to therapy are considered.

Objective: to identify the relationship between the main indicators of iron metabolism and erythrocyte parameters, myeloid and lymphoid cells in patients with sleep disorders in patients with sleep disorders (obstructive sleep apnea (OSA), chronic insomnia (CI), restless legs syndrome (RLS)). Materials and methods: 118 patients, 60 men (50.8%) and 58 women (49.2%), Me age — 47 years (Q1–Q3: 35–61), Me BMI — 25.81 kg/m2 (Q1–Q3: 22.72–29.40) with obstructive sleep apnea (OSA), chronic insomnia, restless legs syndrome in their various combinations. All patients underwent a polysomnographic study, blood cell count, biochemical parameters of iron metabolism were assessed. Results: when assessing the relationship between “Ferritin” and “Hemoglobin”, “Hematocrit (%)”, “Erythrocytes”, “Lymphocytes, abs.”, a moderate direct relationship was established (p<0.001; p<0.001; p=0.001; p< 0.013, respectively).When assessing the relationship between “RDW (%)”, “Neutrophils total, %”, “Neutrophils, abs.” and “%TS”, a moderate inverse relationship was established (p=0.026; p=0.028; p =0.01, respectively).When assessing the relationship between “RDW (%)”, “Neutrophils total, %” and “Serum iron”, a moderate inverse relationship was established (p = 0.003; p = 0.012, respectively). When assessing the relationship between “Lymphocytes, %” and “Serum iron”, a weak direct relationship was established (p = 0.049). Conclusions: in patients with sleep disorders, a statistically significant relationship was revealed between the main parameters of iron metabolism and indicators of “red” blood, the content of neutrophils and lymphocytes. It was shown for the first time that in patients with sleep disorders, changes in the content of neutrophils and lymphocytes may be associated not only with changes in sleep itself, but also with the state of iron metabolism. The complex relationships of iron metabolism, the function of erythrocytes, neutrophils and lymphocytes in patients with sleep disorders can affect the development of both infectious and non-infectious diseases through the mechanisms of maintaining chronic inflammation, hypoferemia, ferroptosis, netosis and other mechanisms.

Болезнь Паркинсона (БП) является хроническим и прогрессирующим нейродегенеративным заболеванием, развивающимся в результате повреждения и гибели дофаминергических нейронов в чёрной субстанции. Клинический диагноз БП определяют спустя много лет от начала развития заболевания, когда значительная часть пула нигростриатных дофаминергичеких нейронов погибает. Возможно, с этим связана относительная низкая эффективность применяемой заместительной терапии в виде леводопасодержащих препаратов. В связи с этим главным приоритетом исследователей является поиск диагностических средств выявления БП на доклинической (продромальной) стадии. Учитывая, что одним из главных механизмов повреждения и смерти нигральных дофаминергических является окислительный стресс, целью данной работы было изучение изменений показателей окислительного стресса в крови пациентов группы риска развития БП, которые могли бы считаться потенциальными диагностическими биомаркёрами на продромальной стадии заболевания. Материалы и методы. В исследовании приняли участие 26 пациентов группы риска развития БП и 20 лиц соответсвующего возраста в качестве группы контроля. Главным критерием включения пациентов в группу риска развития БП явилось наличие расстройств поведения во время сна, нарушение обонятельной функции, вегетативная дисфункция кишечника (запор), а также неврологические и психические расстройства. Общий окислительный статус, общий антиоксидантный статус в плазме крови пациентов группы риска развития БП и группы сравнения определяли спектрофотометрическим методом. Результаты. Показано, что в крови пациентов группы общего риска повышен индекс окислительного стресса и уровень общего окислительного статуса, а также снижен уровень антиокислительного стресса. Заключение. Предполагается, что параметры окислительного стресса могут быть использованы в качестве диагностических биомаркёров на продромальной стадии БП. Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease that results from damage and death of dopaminergic neurons in the substantia nigra. The clinical diagnosis of PD is determined many years after the onset of the disease, when a significant part of the pool of nigrostriatal dopaminergic neurons die. This may be due to the relative low effectiveness of the replacement therapy used in the form of levodopa-containing drugs. In this regard, the main priority of researchers is to search for diagnostic tools for detecting PD at the preclinical (prodromal) stage. One of the main mechanisms of damage and death of nigral dopaminergic neurons is oxidative stress (OS). The purpose of this work wasto study changes in the oxidative stress index, as an integrative parameter of oxidative stress in the blood of patients at risk for developing PD, which could be considered potential diagnostic biomarkers at the prodromal stage of the disease. Methods: The study involved 26 patients at risk of developing PD and 20 age-matched individuals as a control group. The main criterion for including patients at risk for developing PD was disturbances in sleep behavior, olfactory function, autonomic intestinal dysfunction (constipation), as well as neurological and mental disorders. Total oxidative status, total antioxidant status in the blood plasma of patients at risk for developing PD and the comparison group were determined by the spectrophotometric method. Results. It has been shown that in the blood of patients at risk, the index of oxidative stress and the level of total oxidative status are increased, and the level of antioxidant status is reduced. Conclusion. It is assumed that oxidative stress parameters may be candidates for the role of diagnostic biomarkers at the prodromal stage of PD.

Издание представляет собой учебно-методическое пособие, необходимое при освоении дисциплины «Поликлиническая терапия». Пособие разработано в соответствии с самостоятельно установленным МГУ образовательным стандартом для реализуемых основных профессиональных образовательных программ высшего образования по специальности 31.05.01 «Лечебное дело» (уровень образования – специалитет). Пособие призвано подытожить приобретенные студентами умения и навыки, интегрировать их в общую систему медицинских знаний, полученных в результате изучения патологии, фармакологии и др. теоретических и клинических дисциплин. Пособие предназначено для студентов 5-6 курсов медицинских вузов.

Restless legs syndrome (RLS) is a neurological, sensorimotor disorder. It is characterized by the uncomfortable and unpleasant sensations in the legs which begin or worsen during periods of rest, primarily in the evening or night, and are relieved by movement. Central iron deficiency plays a vital role in the pathogenesis of RLS. There is evidence that chronic inflammation is an additional risk factor for RLS. Anemia is the most common complication and extraintestinal manifestation of inflammatory bowel disease, therefore the prevalence of RLS in these patients is a problem of great interest. In addition, inflammatory bowel disease patients’ sleep disturbances directly influence the disease’s clinical course and can be the preclinical marker of exacerbation. It is essential for clinicians to be aware of RLS as a possible reason for sleep disturbance and as a factor that negatively affects the quality of life in inflammatory bowel disease patients.

Objective. To assess age and sex differences in sleep disorders as risk factors and markers of hypertension (HTN) in 18–39-year old people with normal body weight. Design and methods. We performed a cross-sectional study based on the internet survey of 18–39-year-old people with body mass index of 18–25 kg/m2 (n = 2094). The unvalidated questionnaire included 42 questions about various types of sleep disorders and sleep-associated symptoms (0 — never, 1 — rarely, 2 — from time to time, 3 — quite often, 4 — almost all the time). Results. The probability of detecting HTN in young men with normal body weight is higher than in women with similar characteristics (p < 0,001). In women, the probability of detecting HTN decreases, starting with the youngest category (18–24 years old), reaching a minimum in the age group 30–34 years old and then starts to increase. By the age of 40, the indicators for men and women become similar. Based on a multivariate analysis, the risk of HTN in young people with normal body weight is associated with both gender and age (p = 0,022). The contribution of gender to age-related changes in sleep complaints was found for snoring (p < 0,001), sleep apnea (p < 0,001), early awakenings (p = 0,002). The contribution of gender was also noted for various symptoms — daytime sleepiness, some symptoms of restless legs syndrome (RLS), anxiety, depression, leg cramps (p < 0,001) and nocturnal heartburn (p < 0,001). The contribution of age was noted for snoring (p < 0,001), sleep apnea (p < 0,001), early awakenings (p < 0,001) and for a variety of symptoms — daytime sleepiness, some symptoms of RLS, anxiety, nocturnal cough, and nocturnal choking. Conclusions. Our data can be considered when developing measures for HTN prevention, can be recommended for clinical use, as well as in subsequent clinical studies using validated questionnaires.

Aim. To assess the relationship between different types of sleep disorders, sleep-related symptoms and hypertension (HTN).Material and methods. This cross-sectional study based on the online survey of persons aged 18-39 years with a body mass index of 18-25 kg/m2.Results. According to the results, the HTN risk in persons aged 18-39 years with normal body mass index increases 2 or more times in the presence of various types of sleep disorders and related symptoms. The prevalence of HTGN depends on the patient's phenotype, i.e. from a combination of different types of sleep disorders and sleep-related symptoms.Conclusion. Given the widespread prevalence of various sleep disorders, as well as the relationship between sleep disorders and hypertension in young people, it is necessary to develop preventive measures aimed at reducing the HTN risk by restoring healthy sleep. We also suggest that various sleep disorders may be the primary link in the development of essential HTN.

Cerium dioxide nanoparticles have a special place among engineered nanomaterials due to the wide range of their enzyme-like activities. They possess SOD-, catalase- and peroxidase-like properties, as well as recently discovered phosphatase-, photolyase-, phospholipase- and nuclease-like properties. Advancing biomedical applications of CeO2-based nanozymes requires an understanding of the features and mechanisms of the redox activity of CeO2 nanoparticles when entering the vascular bed, especially when interacting with lipid-protein supramolecular complexes (biomembranes and lipoproteins). In this paper, CeO2 nanoparticles are shown to possess two further types of nanozyme activity, namely lipo- and phospholipoperoxidase-like activities. Compared to a strong blood prooxidant, hemoglobin, CeO2 nanoparticles act as a mild oxidising agent, since they exhibit a 106 times lower, and 20 times lower, prooxidant capacity towards linoleic acid and phosphatidylcholine hydroperoxides, respectively. Compared to the widespread pharmacological preparation of iron, Fe(iii) carboxymaltose (antianemic preparation Ferinject®), the prooxidant capacity of CeO2 nanoparticles towards lipid and phospholipid substrates has been shown to be 102 times lower, and 4 times higher, respectively. The data obtained on the mechanism of the interaction of nanodisperse CeO2 with the main components of biological membranes, lipids and phospholipids enable the substantial expansion of the scope of biomedical applications of CeO2 nanozymes.

Objectives. To identify changes in the biochemical composition of the plasma in a group of patients at risk of developing Parkinson’s disease (PD) at the prodromal stage in comparison with age-matched controls. Materials and methods. Subjects in the risk group were selected on the basis of the having impairments to sleep, olfaction, and peristalsis. The risk group consisted of 12 people and the control group of eight people. Results. The results showed that of seven catecholamines and their metabolites, the only blood change was in the L-dihydroxyphenylalanine (L-DOPA) level, which decreased in the risk group from the level in controls. A decreased L-DOPA concentration is regarded as a marker for selective degeneration of central and peripheral catecholaminergic neurons in PD. In contrast to L-DOPA, the blood concentrations of seven of 12 sphingomyelins increased. Given that changes in sphingomyelin metabolism are linked with apoptosis, autophagy, and synucleinopathies, increases in their concentrations in the risk group are regarded as indicators of systemic degeneration of central and peripheral neurons. Furthermore, the risk group showed a tendency to decreased urate concentrations, which are endogenous neuroprotectors. Conclusions. The results obtained here suggest that changes in blood L-DOPA, sphingomyelin, and urate levels can serve as diagnostic markers for the development of PD at the prodromal stage.

The risk factors, clinical manifestations, pathophysiology, diagnosis and treatment options for central sleep apnea and Cheyne-Stokes respiration in patients with heart failure are highlighted in this review. The effectiveness and prospects of therapeutic approaches are discussed: CPAP therapy, adaptive servo ventilation, transvenous stimulation of the phrenic nerve.

The paper summarizes the literature and author's data on the development of early (preclinical) diagnosis of Parkinson's disease (PD). Implementation of this diagnosis will promote the use of preventive therapy and change investments in diagnosis and treatment of patients. The paper declares that at present the only approach to early diagnosis of PD is positron-emission tomography of the nigrostriatal dopaminergic system, but it cannot be used for preventive examination due to its high cost. The authors consider that a less specific, but more promising approach to the development of early diagnosis of PD is the search for markers in body fluids, mainly in the blood, in patients at the prodromal stage of PD. Indeed, a number of markers as changes in the level of metabolites of monoamines, sphingolipids, urates, and indicators of oxidative stress were found in patients selected for the risk group of the prodromal stage of PD, according to characteristic premotor symptoms. In addition, it is assumed that the search for blood markers at an earlier - pre-prodromal stage is possible only in animal models of PD at the early preclinical stage. This approach can also be used to verify blood markers identified in patients at the clinical stage of PD. It is also evident that the complex socio-economic factors influencing the incidence of PD is different in developed versus developing countries. The societal and medical costs of Parkinson's are huge and efforts to improve early preclinical diagnosis of PD will lead to considerable economical and societal benefits. For instance this will allow efficient selection of patients for preclinical diagnostic tests. To assess the effectiveness of this strategy considering the uncertainty of socio-economic issues, a modification of the «cost-utility» analysis is proposed. For the first time, a Markov model of PD including preclinical diagnostic tests and possible neuroprotective therapy was developed and studied. Analytical outcomes of this process suggest that the idea of developing a new multimodal strategy is promising from a socio-economic point of view.

Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as "cytokine storm", and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group). The study primary endpoint was the aggregate dynamics of patients' condition as evaluated by an original CCS-COVID scale, which included, in addition to the clinical status, assessments of changes in the inflammation marker, C-reactive protein (CRP); the thrombus formation marker, D-dimer; and the extent of lung injury evaluated by computed tomography (CT). Patients had signs of lung injury (53.2 % and 25.6 %), increases in CRP 27 and 19 times, and a more than doubled level of D-dimer (to 1.41 µg/ml and 1.15 µg/ml) in the active therapy and the control groups, respectively. The GCS treatment group had a more severe condition at baseline.Results The GCS pulse therapy proved effective and significantly decreased the CCS-COVID scores. Median score difference was 5.00 compared to the control group (р=0.011). Shortness of breath considerably decreased; oxygen saturation increased, and the NEWS-2 clinical status scale scores decreased. In the GCS group, concentration of CRP significantly decreased from 134 mg/dl to 41.8 mg/dl (р=0.009) but at the same time, D-dimer level significantly increased from 1.41 µg/ml to 1.98 µg/ml (р=0.044). In the control group, the changes were nonsignificant. The dynamics of lung injury by CT was better in the treatment group but the difference did not reach a statistical significance (р=0.062). Following the GCS treatment, neutrophilia increased (р=0.0001) with persisting lymphopenia, and the neutrophil/lymphocyte (N/L) ratio, a marker of chronic inflammation, increased 2.5 times (р=0.006). The changes in the N/L ratio and D-dimer were found to correlate in the GCS pulse therapy group (r =0.49, p=0.04), which underlined the relationship of chronic autoimmune inflammation with thrombus formation in COVID-19. No significant changes were observed in the control group. In result, four patients developed venous thromboembolic complications (two of them had pulmonary artery thromboembolism) after the GCS pulse therapy despite the concomitant antiplatelet treatment at therapeutic doses. Recovery was slower in the hormone treatment group (median stay in the hospital was 26 days vs 18 days in the control group, р=0.001).Conclusion Pulse therapy with high doses of GCS exerted a rapid anti-inflammatory effect but at the same time, increased the N/L ratio and the D-dimer level, which increased the risk of thromboembolism.

Background. Excessive daytime sleepiness is a very important symptom of a wide range of pathological conditions and has a significant impact on both the individual patient and the society as a whole. Estimation of the prevalence of excessive daytime sleepiness, identifying the cause, and also its elimination is an important socio-economic task.Objective to estimate the prevalence of excessive daytime sleepiness in the population of the Russian Federation according to the Internet survey data and the distribution of the estimate of the daytime sleepiness by age and body mass index.Materials and methods. One-time study according to the Internet survey data on the Epworth drowsiness scale (ESS).Results. Excessive daytime sleepiness (more than 10 points on the ESS scale) was observed in 40,9% of respondents.Conclusion. According to the results of the study, excessive daytime sleepiness is widespread in the Russian Federation, which speaks of its socio-economic significance, the need for measures to identify its causes and their elimination.

Restless leg syndrome (RLS) is a chronic sensory‑motor disorder characterized by sensory discomfort in legs, appearing or worsening during rest in the evening or night time, evoking the urge to move. Despite its wide prevalence (around 5−10% in the population) and essential influence on the quality of life, not all the physicians, specialists of the primary care and even neurologists are common with this disorder. Because of that RLS stays commonly unrecognized.

The results of study on the sleep–wakefulness cycle in experimental models of the preclinical and early clinical stages of Parkinson’s disease are presented and compared with clinical examples. The conclusion is made that the enhancement of behavioral activity and decrease in the total duration of the slow-wave and paradoxical sleep in model animals occur at the same circadian period of the secretion of pineal melatonin as sleep disorders in patients.