Among the various causes of acute vestibular vertigo, vascular factors are of particular importance. Numerous studies show that the diagnosis of vascular vertigo remains inadequate, often leading to overdiagnosis of stroke and transient ischemic attacks in patients with peripheral vestibular disorders and vestibular migraine, on the one hand, and underestimation of the importance of cerebrovascular pathology, especially in patients with the first attack of persistent vestibular vertigo, on the other.

The International Barany Society has developed and published diagnostic criteria for vascular vertigo. These criteria are intended to facilitate the identification of vascular causes of acute vestibular syndrome. Particular emphasis is placed on clinical signs because imaging techniques often do not allow detection of foci small in volume and area, especially in cases when stroke is manifested by an isolated vestibular syndrome. Key clinical signs to analyze when a vascular etiology of acute vestibular syndrome is suspected include nystagmus, corrective saccades on the Halmagyi test, smooth visual pursuit, visual saccades, severity of trunk ataxia, and hearing loss.

Work stress is a discrepancy between the workload and the individual's ability to do their job. Work stress factors that cause work stress are individual, work, and outside the work/environment. There is no data and research about work stress from work factors, mainly focusing on lecturers or universities.

Objective. This study aimed to analyze the relationship between work factors in the form of type of faculty, workload, type of professor, and interpersonal relationships with the work stress of lecturers.

Material and methods. This research was conducted using a cross-sectional study. The research sample consisted of 100 lecturers with active status selected by quota sampling. Data were collected using a questionnaire filled out online and analyzed using the Chi-square test and the Contingency Coefficient Test.

Results. The result showed that most participants had moderate stress (score: 59–92) and moderate workload (score: 50–80). Most of the participants were Associate professors (52%) and had good interpersonal relationships in the workplace (59%). There is a relationship between interpersonal relationships and work stress of lecturers. However, there was no relationship between type of faculty, workload, and type of professor with lecturers' work stress.

Conclusion. In conclusion, interpersonal relationships are significantly related to job stress on lecturers. A good interpersonal relationship will reduce the possibility of work stress on the participant.

Objective: to determine the main psychosocial factors associated with sleep disorders in an open population aged 25–64 years in Novosibirsk.

Material and methods. Screening studies were conducted on representative samples of the population aged 25–64 years: in 2013–2016. (V screening: 427 men, mean age 34±0.4 years, response rate 71%; 548 women, mean age 35±0.4 years, response rate 72%); in 2015–2018 (VI screening: 275 men, mean age – 49±0.4 years, response rate – 72%; 390 women, mean age – 45±0.4 years, response rate – 75%) (budget topic No. АААА-А17-117112850280-2) using the protocol of the WHO international program “MONICA-psychosocial”. The Jenkins questionnaire was used in the population survey to investigate sleep disorders. To examine personal anxiety, a form of the Spielberger Self-Assessment Scale was used; to determine depression, life exhaustion, and hostility, the MOPSY-test was used; and to examine social support, the Berkman-Syme test was used.

Results. In the open population aged 25 to 64 years, sleep disorders were found in 47.6% of men and 51.2% of women. Among those with sleep disorders, we found high levels of: anxiety (HLA) in 61.8% of men (χ²=56.169; df=4; p<0.001) and 68.1% of women (χ²=36.535; df=4; p<0.001); depression (HLD) – in 18.2% of men (χ²=26.609; df=4; p<0.001) and 20% of women (χ²=41.041; df=4; p<0.001); vital exhaustion (VE) – in 63.6% of men (χ²=93.378; df=4; p<0.001) and 59.3% of women (χ²=124.115; df=4; p<0.001); hostility (HLH) – in 52.7% of men (χ²=17.598; df=4; p<0.001) and 39.3% of women (χ²=13.139; df=4; p<0.01).We found no statistically significant differences between groups of men and women, who differed in sleep self-essessment and indicators of the index of close contacts and the index of social ties.

Sleep disturbances increased the likelihood of developing of VE (OR 2.301; 95% СI 1.774–2.984; p<0.0001), HLA (OR 1.882; 95% CI 1.199–2.955; p<0.006), depression (OR 1.423; 95% CI 1.099–1.842; p<0.007). In men, sleep disturbances contributed to: HLA (OR 2.477; 95% CI 1.303–4.709; p<0.006), VE (OR 2.282; 95% CI 1.529–3.404; p<0.0001). In the group of women with sleep problems, the probability of VE increased (OR 2.37; 95% CI 1.669–3.366; p<0.0001).

Conclusion. The study found that in an open population aged 25–64 years with sleep disorders, there was a high level of psychosocial factors and that the presence of sleep disorders increased the likelihood of developing psychosocial factors.

Therapy of depression is a current problem in psychiatry. Agomelatine is not inferior to other modern drugs in terms of antidepressant efficacy (response and remission rates) and is characterized by the best tolerability.

Objective: to evaluate the efficacy and safety of agomelatine in the treatment of nonpsychotic depression with a single and recurrent course.

Material and methods. Patients (n=37) with a current depressive episode (DE; F32 according to ICD-10), mean age 41.2±2.07 years, were studied. Clinical psychopathological and psychometric methods were used in the study (Hamilton Hospital Depression Scale – HAMD-17; Spielberger–Khanin Anxiety Self-Assessment Scale, Sheehan Anxiety Scale, Clinical Global Impression Scale – CGI-I). A single DE was diagnosed in 62.2% of patients, and recurrent depressive disorder in 37.8%. Stress-related onset of current DE was found in 56.8% of cases, autochthonous in 43.2%.

Results. 94.6% of patients were responders, including 68.6% who went into remission. A statistically significant decrease in scores on the HAMD-17 scale was noted in the remission group from the 7^th day of agomelatine therapy (p<0.05), in the responder group – from the 14^th day of therapy (p<0.05). According to the Sheehan scale, a statistically significant decrease in scores was noted at the end of the first week of therapy (p<0.05), according to the Spielberger–Khanin scale – in the second week (p<0.05) in all patients. According to the CGI-I scale, the condition at the end of therapy improved in 57.1% of patients, significantly in 42.9%. Clinical predictors of therapeutic response in patients with remission included significantly higher frequency of a single DE (p<0.02), moderate severity of current depression (p<0.02), dizziness among autonomic disorders (p<0.01), a significantly lower representation of the melancholic type of depression (p<0.05), a symptom of a gloomy and pessimistic vision of the future (p<0.05), sleep disturbances (p<0.04), a factor of personal significance in the form of a threat in patients with stress-provoked onset of the current DE (p<0.05).

Adverse events occurred in the first week of treatment with agomelatine in 14.3% of cases (nausea – 8.6%, headache and dizziness – 2.9% each), they were mild and did not require discontinuation of the drug. Two patients taking agomelatine at a dose of 50 mg discontinued the study: in one case persisted social phobia, increased fatigue, motor retardation, and persistent modern insomnia; in the other case – a pronounced senestoalgic syndrome with cerebral localization.

Conclusion. Agomelatine therapy has been shown to be highly effective and well tolerated in nonpsychotic depression.

Cerebral ischemic events, including ischemic stroke (IS) and transient ischemic attack (TIA), are among the most common extracardiac complications of infective endocarditis (IE).

Objective: to evaluate cerebral ischemic events (prevalence, clinical and neuroimaging characteristics, predictors, prognosis) in patients with “left-sided” IE, who underwent cardiac surgery, according to the registry of the Federal Center for Cardiovascular Surgery.

Material and methods. A retrospective review of data from the hospital information system was performed in one of the federal centers for cardiovascular surgery of the Russian Ministry of Health. Inclusion criteria in the study: age of patients ≥18 years, significant or probable (Duke criteria) IE of the left heart – aortic and/or mitral valves. Patients with isolated right heart IE (tricuspid valve, pacemaker-associated endocarditis), nonbacterial thromboendocarditis, and chronic IE were excluded from the study. For the analysis, 222 cases of IE in 216 patients were used. IS was observed in 43 (19.4%) patients with “left-sided” IE, TIA – in 4 (1.8%). In ²/₃ of cases, patients suffered a minor stroke (NIHSS <5), while every fifth patient had symptoms of encephalopathy. Logistic regression was used to determine the predictors of cerebral embolism. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each of the significant risk factors, and time to first clinical event (death) was estimated using the Kaplan–Meier method.

Results. On neuroimaging in IE, the following signs were frequently detected: involvement of different cerebral vascular territories (65.1%), multifocal (≥1 focus) infarcts (74.4%), hemorrhagic transformation (37.2%). Cortical and/or subcortical distribution of infarcts was observed in 97.7% of patients. According to multivariate analysis, IS and TIA were predicted by vegetations >10 mm (OR 3.552; 95% CI 1.066–11.8463; p=0.039), mobile vegetations (OR 6.112; 95% CI 1.105–33.784; p=0.038) and multiple vegetations (OR 5.2 08, 95% CI 1.189–22.805, p=0.029). The impact of cerebral embolism on prognosis (in-hospital and long-term mortality) in patients undergoing cardiac surgery was not established.

Conclusion. According to the neuroimaging data, cerebral infarcts in IE correspond to the main signs of cardioembolism. The characteristics of the vegetations (size >10 mm, mobility, multiplicity) are a crucial indicator of the embolic potential of IE.

Stroke is one of the leading causes of death and primary disability and contributes significantly to the global burden of disease. Identification of individuals at high risk of ischemic stroke (IS) is an important component of disease prevention. The differences between risk factors (RF) for stroke in men and women are not well understood.

Objective: to determine the predictive value of RF for the development of IS in men and women aged 45–74 years.

Material and methods. The study included 728 patients (380 men and 348 women) aged 45–74 years, including 392 patients (247 men and 145 women) with IS in the carotid artery basin (main group) and 336 patients (133 men and 203 women) with vascular cognitive impairment (comparison group). To build predictive models to assess the impact of RF on the development of IS in men and women, we used the logistic regression method with stepwise exclusion of variables according to the Wald algorithm.

Results. The predictive regression model of IS in men includes atherosclerotic stenosis of the internal carotid arteries [odds ratio (OR) 3.571; 95% confidence interval (CI) 1.792–7.114], in a predictive regression model in women – diabetes mellitus type 2 (OR 5.074; 95% CI 1.768–14.561) and a history of IS (OR 6.857; 95% CI 1.825–25.762). Other risk factors for the development of IS (atrial fibrillation, history of transient ischemic attack, arterial hypertension stage) affected both men and women.

Conclusion. Atherosclerotic stenosis of the internal carotid arteries was found to be a sex-specific prognostic factor for IS in men, and type 2 diabetes mellitus and a history of IS in women.

The issue of the influence of women's mental state on their reproductive function has not been adequately addressed and requires further research.

Objective: a comparative evaluation of individual indicators of menstrual and reproductive function in mentally healthy and mentally ill women with infertility.

Material and methods. We studied 348 women aged 21 to 40 years with primary and secondary infertility, 120 of whom had been treated for a mental disorder in a psychiatric hospital prior to the present study. The patients' condition was assessed by a clinical method using a specially designed questionnaire card.

Results. Reproductive function of patients in the studied groups differed significantly in several indicators. Mentally ill women with primary infertility are characterized by the following features: later onset of menstruation, scanty or heavy menstrual flow (p<0.05), irregularity or absence of menstruation during the period of exacerbation of the disease, insufficient emotional response to menarche (p<0.05), irregularity of sexual life and dissatisfaction with it (p<0.01). Spontaneous miscarriages and stillbirth occurred more frequently in mentally ill women, especially in women with endogenous disorders (schizophrenia, affective disorders), while abortions and gynecological surgeries were more frequent in mentally healthy women (p<0.001). Predictors of infertility on the part of mental health are the early onset and chronic course of a mental disorder, the severity and duration of an exacerbation of the illness, brief and incomplete remissions, the development of personality changes or a defect (schizophrenic) as a result of a mental illness.

Conclusion. Menstrual and reproductive functions of women depend on their mental state. In women with mental disorders, menstrual dysfunction together with psychopathological symptoms of illness (decrease in libido, communication, emotional numbness), decrease in social and family adaptation leads to impairment of reproductive function.

Objective: to evaluate the pharmacokinetic parameters, safety and tolerability of Vespireit^® (INN buspirone), prolonged-release tablets, 15 mg (JSC “Valenta Pharm”, Russia), which is being developed as a drug for the treatment of functional vertigo, in healthy volunteers with a single oral dose of 15 and 30 mg on an empty stomach or after meals and multiple doses in a daily dose of 15 mg.

Material and methods. JSC “Valenta Pharm” conducted an open-label, three-stage, randomized, two-periods, cross-over comparative clinical trial of Vespireit^®. At stages 1 and 2, healthy volunteers were screened and randomized into two equal groups (Group 1 and Group 2), as well as the distribution of participants in Group 3. Then, at stage 1, healthy volunteers (n=24) took Vespireit^® once at a dose of 15 mg on an empty stomach or after meals, at stage 2, volunteers (n=24) took Vespireit^® once at a dose of 30 mg on an empty stomach or after meals. Stage 3 was conducted in 18 volunteers as a non-randomized, non-comparative study with Vespireit^® 15 mg on an empty stomach once daily for 5 days. During the study, blood samples were collected from each subject to determine the concentration of test compounds in blood plasma and subsequently calculate their pharmacokinetic parameters. Quantitative determination of buspirone and its two metabolites, 6-hydroxybuspirone (6OH-bus) and 1-(2-pyrimidinyl)-piperazine (1-PP), was performed by a validated high-performance liquid chromatography method with tandem mass spectrometric detection. During the study, tolerability and safety were also evaluated: adverse events, vital signs, laboratory parameters and electrocardiogram parameters were recorded.

Results. When the study drug Vespireit^®, prolonged-release tablets, was administered once at a dose of 15 mg to healthy volunteers after a meal, an increase in the relative bioavailability and relative degree of absorption of buspirone was observed compared with the fasting state, which was accompanied by a 1.5- and 2.5-fold increase in the AUC_0–t and C_max of buspirone, respectively. In addition, the C_max of 6-OH-bus increased 1.4-fold and the C_max of 1-PP increased 1.2-fold. Meal had no effect on the AUC_0–t of 6-OH-bus and 1-PP. When the study drug was administered once at a dose of 30 mg after a meal, an increase in the relative bioavailability and relative degree of absorption of buspirone was observed compared with fasting, which was accompanied by an increase in the AUC_0–t and C_max by 1.5- and 2.1-fold, respectively. A 1.2-fold increase in the C_max of 6-OH-bus was also observed. Food had no effect on the AUC_0–t of 6-OH-bus and on the AUC_0–t and C_max of 1-PP. No accumulation of buspirone and its metabolites was observed with repeated dosing.

Conclusion. In the study, the values of pharmacokinetic parameters of the new drug Vespireit^® in the prolonged-release tablets dosage form were determined both with single administration on an empty stomach and after meals and with multiple administration. The differences and advantages over buspirone preparations in the form of immediate-release tablets are shown: higher relative bioavailability of buspirone with a reduction in interindividual differences in bioavailability and C_max, more stable plasma concentration of buspirone with reduced peak values of the active substance and metabolite 1-PP, a 1.2-fold increase in AUC_0–∞, a 2-fold increase in T_1/2, and a 2-fold increase in the degree of retardation (MRT) for buspirone, a 1.4-fold increase in C_max and MRT of 6-OH-bus, a decrease in AUC_0–∞, AUC_0–t, and T_1/2 of metabolite 1-PP, and a decrease in the ratio of the concentration of 1-PP to the concentration of buspirone and to 6-OH-bus. A favorable safety profile of Vespireit^® was demonstrated.

Persistent postural perceptual dizziness (PPPD) is the most common cause of vague chronic vertigo and severely limits patients' quality of life.

Limited data are available on comorbidities, the typical treatment of patients with PPPD, and the efficacy of combination therapy for PPPD.

Objective: to identify comorbid disorders and evaluate the efficacy of complex therapy in patients with PPPD.

Material and methods. Sixty patients (mean age 42.5±13.8 years) with PPPD were studied. All patients were prescribed complex treatment that included antidepressants (selective serotonin reuptake inhibitors), vestibular exercises, and an educational program. In 28 patients, Arlevert (combination of cinnarizine 20 mg + dimenhydrinate 40 mg) was used as drug therapy. A clinical otoneurologic examination, videonystagmography, assessments by Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Spielberger State-Trait Anxiety Inventory (STAI), Dizziness Handicap Inventory (DHI) and otoneurologic examination were performed at baseline and at the end of treatment (mean, one month).

Results. All patients had previous misdiagnoses, among which vertebrobasilar insufficiency and chronic cerebral ischemia predominated. Thirty two (53.33%) patients with PPPD had anxiety-depressive disorders (ADD) as the main comorbidity, 20 (33.33%) patients had migraine, 8 (13.33%) patients had previously had peripheral vestibular disorders that were not diagnosed. The severity of dizziness according to the otoneurological questionnaire and the DHI decreased after one month of therapy in the group with PPPD and ADD from 44.00±16.80 to 29.6±12.80 points (p<0.001), in the group with PPPD and peripheral vestibular disorders – from 49.20±14.04 to 31.60±17.69 points (p<0.001), in the group with PPPD and migraine – from 43.58±16.28 to 28.50±7.20 points (p<0.001). The severity of anxiety and depression according to BAI decreased in the group with PPPD and ADD from 30.00±6.99 to 16.12±4.16 points (p<0.001), in the group with PPPD and peripheral vestibular disorders – from 28.40±8.35 to 16.60±4.62 points (p<0.001), in the group with PPPD and migraine – from 24.11±3.80 to 14.26±3.43 points (p<0.001). The severity of depression according to BDI decreased in the group with PPPD and ADD from 9.62±5.26 to 6.25±3.20 points (p<0.001), in the group with PPPD and peripheral vestibular disorders – from 14.80±8.26 to 8.40±5.37 points (p<0.001), in the group with PPPD and migraine – from 11.32±5.10 to 6.53±3.44 points (p<0.001). The severity of anxiety according to HADS decreased in the group with PPPD and ADD from 13.75±3.20 to 9.25±2.43 points (p<0.001), in the group with PPPD and peripheral vestibular disorders – from 12.40±5.77 to 7.80±3.83 points (p<0.001), in the group with PPPD and migraine – from 14.26±3.16 to 8.74±2.18 points (p<0.001).The severity of depression according to HADS decreased in the group with PPPD and ADD from 4.88±4.12 to 3.88±3.09 points (p<0.001), in the group with PPPD and peripheral vestibular disorders – from 8.40±3.58 to 5.60±2.88 points (p<0.001), in the group with PPPD and migraine – from 5.74±3.11 to 3.47±2.32 points (p<0.001). Situational anxiety according to STAI decreased in the group with PPPD and ADD from 47.62±6.57 to 40.12±3.68 points (p<0.001), in the group with PPPD and peripheral vestibular disorders – from 58.20±7.85 to 48.00±7.65 points (p<0.001), in the group with PPPD and migraine – from 46.26±7.01 to 35.68±5.11 points (p<0.001). Personal anxiety according to STAI decreased in the group with PPPD and ADD from 52.25±10.73 to 42.12±7.06 points (p<0.001), in the group with PPPD and peripheral vestibular disorders – from 58.40±5.64 to 48.60±6.77 points (p<0.001), in the group with PPPD and migraine – from 53.32±8.78 to 40.63±5.60 points (p<0.001).

Conclusion. Patients with PPPD are often misdiagnosed with cerebrovascular disease. The most common comorbid disorders in PPPD are anxiety disorders and migraine, and less commonly peripheral vestibular disorders. An integrated approach to the management of patients with PPPD, including treatment of comorbid disorders, is effective.

Cardiovascular factors significantly increase the risk of vascular cognitive impairment (VCI). Currently, there are no specific treatments for VCI. A promising therapeutic strategy is the administration of citicoline, which has a neuroprotective effect.

Objective: to evaluate the effect of treatment with citicoline (Noocil^®) on cognitive function and quality of life (QoL)in patients with mild cognitive impairment (MCI) developed in a background of arterial hypertension and cerebral arteriosclerosis.

Material and methods. An open-label prospective observational study enrolled 32 patients with neuroimaging-confirmed vascular cognitive impairment who received baseline therapy (antihypertensive, lipid-lowering, and antiplatelet therapy) and achieved target blood pressure and low-density lipoprotein cholesterol levels. All patients were assessed with a neuropsychological status assessment (MoCA-test). The efficacy of therapy was assessed by the Short Form-36 Quality of Life Questionnaire (SF-36).

Results. The most common complaints of the patients were poor concentration, fatigue, forgetfulness, mood lability, sleep disturbances, more often in the form of early waking, and headaches. After 3 months of taking the drug Noocil^®, all patients noted an increase in the ability to work, an improvement in concentration, memory and reproduction of the information received, both physical and mental indicators of QoL improved. The positive dynamics in terms of cognitive status (especially the functions of attention, short-term memory, several aspects of executive functions), QoL of patients, which was associated with the effect of Noocil^® therapy, was accompanied by the absence of adverse events. A distinctive feature of domestic citicoline (Noocil^®) is the presence of an original dosage form – a 240 ml bottle for oral administration, which improves adherence to long-term therapy.

Conclusion. The efficacy, safety and good tolerability of Noocil^® therapy in patients with predemental VCI was demonstrated.

Objective: to study the pharmacokinetic parameters and safety of Dorsumio^® (mirtazapine + tizanidine, extended-release tablets, 15 mg + 6 mg, JSC Valenta Pharm, Russia) taken once by healthy volunteers in comparison with Calixta^®, a monocomponent drug (INN: Mirtazapine, filmcoated tablets, 30 mg, Belupo, Drugs and Cosmetics d.d., Republic of Croatia) and Sirdalud^® MR (INN: Tizanidine, modified-release capsules, 6 mg, Novartis Pharma AG, Switzerland) with an evaluation of their drug interactions when taken concomitantly or separately.

Material and methods. A two-stage, randomized, comparative cross-over study of the pharmacokinetics and safety of the complex drug Dorsumio^® was conducted. In the first stage, volunteers alternated between taking one or two tablets of the study drug in two administration periods; in the second stage, subjects alternated between taking the reference monodrugs Calixta^® and Sirdalud^® MR alone and in a joint combination in three administration periods. A total of 38 volunteers were randomized into the study, of which 14 subjects participated in the first and 24 in the second stage of the study. Quantitative levels of mirtazapine and tizanidine were determined by high-performance liquid chromatography with tandem mass spectrometry. Based on the data obtained, the main pharmacokinetic parameters reflecting the bioavailability of each drug were calculated, and the mutual influence of their combination on pharmacokinetics was also studied. During the study, vital signs and laboratory parameters of the subjects were monitored, and the occurrence of adverse events (AEs) and serious AEs was recorded.

Results. A two-fold increase in the dose of the combination drug Dorsumio^® resulted in a comparable increase in the pharmacokinetics of the individual drugs. There was no significant reciprocal effect of mirtazapine and tizanidine on their pharmacokinetic parameters. In one of the subjects participating in the second stage of the study, two mild side effects were registered after the joint use of Calixta^® and Sirdalud^® MR that did not require medical intervention and resolved on their own without health consequences.

Conclusion. There were no differences in the safety profile of the combined use of mirtazapine and tizanidine in the form of a free or fixed combination. It was shown that the investigated drug combination had no mutual influence on the pharmacokinetics of the individual components.

pathological hormone secretion, the clinical presentation is determined by the localization of the tumor. Common symptoms include headache and visual field defects. This review addresses the pathology aspects of diagnosis, conservative treatment, and methods of radiation therapy. Drug therapy of endocrine-inactive adenomas is based on the presence of receptors for somatostatin and dopamine in pituitary adenoma cells. Data on stereotactic radiosurgery techniques such as gamma and cyberknife and disease prognosis are presented.

To date, there is no accepted highly specific pattern for the detection of multiple sclerosis. Correct diagnosis is particularly difficult in situations where an atypical clinical picture of the disease is observed or nonstandard neuroimaging patterns are detected. Therefore, the scientific community has high hopes for the discovery of new markers that will allow clarification of the diagnosis in controversial cases. Currently, there is a lot of research focused on the study of an additional diagnostic MRI pattern – a sign of a paramagnetic rim. This symptom is associated with chronic smoldering central nervous system (CNS) lesions, is more commonly seen in young males, is found primarily in the periventricular region, and is also a promising predictor of disability and cognitive impairment. There is evidence that it is present in earlier stages of disease in “fresh” lesions of the CNS. However, further studies are needed to use this diagnostic MRI pattern in clinical practice.

Trimethylamine-N-oxide (TMO) is one of the best studied metabolites of the gut microbiota. It increases the risk of stroke and dyscirculatory encephalopathy, independent of traditional cardiovascular risk factors. The mechanisms of the negative effects of TMO on the cardiovascular system are related to the acceleration of atherosclerosis progression, platelet activation, and the development of aseptic inflammation. Currently, elevated TMO levels are an indication for a strict diet with restriction of foods rich in TMO precursors. Future research should clarify the role of TMO in the development of cerebrovascular disease (CVD). It is necessary to continue the investigation of new compounds that can reduce TMO levels in patients at high risk for developing CVD.

Understanding the major pathological pathways and the key molecules involved in the pathogenesis of inflammatory processes in joints, particularly in osteoarthritis (OA), is crucial for drug and pharmaconutraceuticals development. OA is a degenerative joint disease that predominantly affects articular cartilage. Destruction of hyaline cartilage and restructuring of subchondral bone are accompanied by synovial inflammation in the joint, including the facet joint of the spine, manifested by pain in the joint, low back pain (LBP), and limitation of functional activity. The article discusses the relationship between immune and inflammatory mechanisms in OA of any location, including the joints of the spine. One of the mechanisms for the formation of a “vicious circle of inflammation” during the activation of discoidin receptors by endogenous type II collagen is discussed, leading to the induction of the synthesis of pro-inflammatory mediators: tumor necrosis factor α(TNFα), metalloproteinases (MMPs) 1 and 13, interleukins (IL) 1 and 6. Inflammation, in turn, leads to a decrease in the synthesis and destruction of endogenous type II collagen and, subsequently, to cartilage destruction. Cartilage fragments entering the joint space of the intercellular matrix enhance the synthesis of TNFα, IL, and MMP and exacerbate the inflammatory process. Oral ingestion of exogenous undenatured type II collagen(NK-II) helps, first, to inactivate the binding of fragments of destroyed endogenous type II collagen to discoidin receptors and to break the "vicious circle of inflammation"; secondly, through the mechanism of oral/intestinal tolerance via the lymphoid system in Peyer's patches of the small intestine, leads to the activation of immune cells (T-lymphocytes) and initiation of the immune response – the synthesis of anti-inflammatory mediators (transforming growth factor β, IL4 and IL10). The new pharmaconutraceutical Chondroguard^®TRIO, which contains chondroprotectors (chondroitin sulfate and glucosamine sulfate) as well as NK-II, will make it possible to influence the key sites of the pathological process in OA.