Neuroinflammation in Obese Children.

Obesity is associated with chronic persistent inflammation due to a pool of tissue macrophages that can penetrate the blood-brain barrier and cause neuroinflammation. The analysis of the association of CD14+CD163+ monocytes in the peripheral blood with cognitive functions in 56 obese children (mean age 11.95 (9.45; 14.45) years) was carried out. The control group consisted of 10 children (mean age 10.4 (9.3; 13.8) years). Standard deviation of the body mass index (SDS BMI) and height (SDS height) were calculated using WHO AnthroPlus software (for children of 6-19 years). Body composition was assessed using bioimpedance measurement. Mononuclear cells were isolated from whole blood by centrifugation on a Ficoll-Urografin density gradient (ρ=1.077 g/ml). The content of CD14+CD163+ monocytes in the peripheral blood was assessed by flow cytometry. To analyze cognitive functions, the intelligence coefficient (IQ) was calculated and a Russian adaptation of the Rey test was performed. We found an increase in the number of M2-polarized CD14+CD163+ monocytes in the peripheral blood with an increase in the obesity degree and in the presence of cognitive decline, as well as a negative correlation of the level of M2-polarized monocytes and IQ, taking into account the excess of visceral fat. The revealed data on the relationship of M2-polarized CD14+CD163+ peripheral blood monocytes with obesity in children and the development of neuropsychological deficiency confirm the role of peripheral visceral obesity and neuroinflammation.

Effect of Gonadotropin-Releasing Hormone Antagonist on the Expression Patterns of Insulin-Like Growth Factor 1, Androgen Receptor, and Luteinizing Hormone Receptor in an Experimental Rat Model of Functional Ovarian Cysts.

We studied the expression of insulin-like growth factor 1 (IGF-1), androgen receptor (AR) and luteinizing hormone receptor (LHR) in the ovaries under the conditions of the modeling and subsequent treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist (ant-GnRH). The intensity of IGF-1, LHR, and AR expression in the generative elements of rat ovaries changed under conditions of functional ovarian cysts simulation, as well as during treatment with ant-GnRH. In both experimental groups, the expression levels of the studied markers in preantral follicles and epithelial lining of cysts were found to be related to the number of growing follicles and cysts. A divergence of LHR and AR expression indices and a more pronounced decrease in the number of cystic cavities were observed in the group receiving ant-GnRH. These changes demonstrate a positive effect of ant-GnRH on intra-ovarian regulatory factors and a therapeutic effect in functional ovarian cysts.

Morphofunctional State of the Ovaries in Rats with Experimental Model of Functional Cysts and Their Treatment with Gonadotropin-Releasing Hormone Antagonist.

The morphofunctional features of the ovaries were evaluated in rats with functional ovarian cysts model treated with gonadotropin-releasing hormone antagonist. Administration of the antagonist significantly (p=0.009) reduced the number of cysts and the growth of follicles in the ovaries. The obtained results attest to a possibility of successful treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist.

Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period.

The universal proteinase inhibitor α2-macroglobulin (α2-MG) exhibiting antiviral and immunomodulatory activities, is considered as an important participant in the infectious process. The activity of α2-MG in the new coronavirus infection and post-covid syndrome (long COVID) has not been studied yet. We examined 85 patients diagnosed with community-acquired bilateral polysegmental pneumonia developed under conditions of a new coronavirus infection SARS-CoV-2. For assessment of the post-COVID period, 60 patients were examined 5.0±3.6 months after the coronavirus infection. Among these patients, 40 people had complications, manifested in the form of neurological, cardiological, gastroenterological, dermatological, bronchopulmonary symptoms. The control group included 30 conditionally healthy individuals with a negative PCR result for SARS-CoV-2 RNA and lack of antibodies to the SARS-CoV-2 virus. The α2-MG activity in serum samples of patients with coronavirus infection dramatically decreased, up to 2.5% of the physiological level. This was accompanied by an increase in the activity of the α1-proteinase inhibitor, elastase- and trypsin-like proteinases by 2.0-, 4.4- and 2.6-fold respectively as compared with these parameters in conditionally healthy individuals of the control. In the post-COVID period, despite the trend towards normalization of the activity of inhibitors, the activity of elastase-like and especially trypsin-like proteinases in serum remained elevated. In overweight individuals, the increase in the activity of trypsin-like proteinases was most pronounced and correlated with an increase in the antibody titer to the SARS-CoV-2 virus. In the post-COVID period, the α2-MG activity not only normalized, but also exceeded the control level, especially in patients with dermatological and neurological symptoms. In patients with neurological symptoms or with dermatological symptoms, the α2-MG activity was 1.3 times and 2.1 times higher than in asymptomatic persons. Low α2-MG activity in the post-COVID period persisted in overweight individuals. The results obtained can be used to monitor the course of the post-COVID period and identify risk groups for complications.

[Cerebral perfusion and tractography in obese children]. / Rezul'taty izucheniya tserebral'noi perfuzii i traktografii u detei s ozhireniem.

OBJECTIVE: To study the relationship of the structure of the white matter of the brain, neurovascularization and cognitive functions in obese children and adolescents. MATERIAL AND METHODS: The study included 64 obese patients, aged 12-17 years, and 54 children without excess body weight. A general clinical examination, neuropsychological testing (the Raven's test with the calculation of IQ, MoCA, the Rey 15-Item Memory Test (RMT), 1 and 2), magnetic resonance imaging (MR) tractography and contrast-free perfusion of the brain were conducted. RESULTS: Obese children and adolescents had both a decrease in scores on MoCA and the Raven's test, and in terms of IQ, while according to RMT-1, there were significant differences in the two groups, and in RMT-2 the results were comparable. Perfusion analysis showed a decrease in vascularization in the white matter area of the occipital lobe on the left and its increase in the temporal lobe area also on the left. When assessing the white matter according to MR tractography, a decrease in fractional anisotropy was noted in the area of the hook-shaped beam on the right and left, anterior and posterior commissural tracts. These changes were correlated with neuropsychological results. CONCLUSION: In obese children and adolescents, there was a destruction of the integrity of the white matter and neurovascularization of the brain associated with a deficit of cognitive functions.

[Blood pressure variability and brain neuroimaging in patients with type 2 diabetes]. / Variabel'nost' arterial'nogo davleniya i dannye neirovizualizatsii golovnogo mozga u patsientov s sakharnym diabetom 2-go tipa.

OBJECTIVE: To analyse a role of BP (blood pressure) variability in shaping neuroplasticity in patients with type 2 diabetes mellitus (DM). MATERIAL AND METHODS: The study enrolled 100 patients with type 2 DM divided according to the presence of cognitive impairment (CI) and 25 control subjects. Biochemical blood count, plasma osteopontin, 24-hour self-blood pressure monitoring (SBPM) and brain MRI were assessed. RESULTS: Patients with type 2 DM and CI had higher body mass index as well as glycated hemoglobin (HbA1c), glucose, alanine aminotransferase, osteopontin and hyperlipidemia (p≤0.05). There was a significant difference in all standard indices, patients with type 2 DM were classified as «non-dipper¼, and there were significantly higher values of the index of time and area of stay in the state of suprathreshold BP and BP variability at night, as well as the risk of latent arterial hypertension in CI. Neuroimaging assessment revealed decreased blood flow according to contrast and non-contrast perfusion in all parameters in cortical (especially the frontal lobe) and subcortical structures (predominantly in the shell region), and was associated with SMAD parameters. Mean systolic and diastolic BP during the day and night, as well as the variability index, also influenced the integrity between cortico-spinal tract, hook, inferior longitudinal and arcuate fascicles. The same parameters altered hippocampal metabolism in terms of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr), Cho/Cr ratios. CONCLUSION: In patients with type 2 DM, BP variability contributes to CI through a proinflammatory mechanism (osteopontin) leading to brain neuroimaging abnormalities.

[Different types of cognitive rehabilitation in patients with type 2 diabetes]. / Raznye vidy reabilitatsii kognitivnoi disfunktsii u patsientov s sakharnym diabetom 2-go tipa.

AIM: Diabetes mellitus (DM) type 2 leads to the progression of cognitive impairment. The authors compared different types of cognitive rehabilitation in patients with type 2 diabetes. MATERIAL AND METHODS: One hundred and twenty patients with type 2 diabetes were examined and randomized into 4 groups: the computerized training group, the exercise therapy group, the akatinol memantine group and the control group. The duration of rehabilitation was 6 months. All patients underwent general clinical examination and neuropsychological testing. RESULTS AND CONCLUSION: All patients had impaired cognitive functions, especially in visual-constructive skills, speech, abstraction, and memory. Treatment with akatinol memantine was most effective compared to computerized training and exercise therapy. With the exception of the control group, all groups, in particular the exercise therapy group, showed the improvement in carbohydrate metabolism.

[Rare genetic markers of cognitive impairment in diabetes mellitus]. / Redkie geneticheskie markery kognitivnykh narushenii pri sakharnom diabete.

The study of potential mechanisms of cognitive impairments associated with gene expression in patients with diabetes mellitus (DM) is becoming increasingly important due to the increase in the prevalence of dementia in this category of patients. DM is associated with the alteration of neurogenesis, and the variability of glycemia causes the changes in plasma and mitochondria, promotes the formation of free radicals, oxidative stress, activation of apoptosis of neurons, circulation of proinflammatory agents and other pathological factors. The association between diabetes and cognitive impairment is largely mediated by both neurodegeneration markers and cerebrovascular diseases. However, the literature presents conflicting results on the risk and frequency of cognitive impairment in patients with type 1 and 2 diabetes. This is probably explained by limitations and variations of the studies, but also by the contribution of genetic polymorphisms to the development of cognitive impairment in patients with diabetes. This review describes rare genetic markers of cognitive disorders in type 1 and type 2 diabetes as well as their relationship with various parameters of carbohydrate metabolism and clinical manifestations of cognitive disorders.

[Markers for cognitive impairments and variability of glycaemia in patients with type 1 diabetes mellitus]. / Markery kognitivnykh narushenii i variabel'nost' glikemii u patsientov s sakharnym diabetom 1-go tipa.

AIM: To analyze the relationship between the markers of cognitive impairment and the variability of glycaemia in patients with DM type 1. MATERIAL AND METHODS: Patients with DM type 1 and people without DM (the control group) were examined. Neuropsychological testing (MoCA-test), brain MRI and proton magnetic resonance spectroscopy of the brain, as well as parameters of carbohydrate metabolism (fasting blood glucose, glycated hemoglobin and glycemic variability coefficients) were used. RESULTS AND CONCLUSION: Data on the decrease in the overall performance of the MoCA-test (in particular, on assignments to memory and attention domains), atrophic changes in the cerebral cortex and violations of the content of the main metabolites of brain cells in patients with DM type 1 in comparison with the control group were obtained. A number of positive and negative correlations between these disorders and coefficients of glycemic variability were found in patients with DM type 1. The results suggest a significant negative effect of high levels of glycaemia variability on cognitive functions in patients with DM type 1.