OBJECTIVE:To evaluate the clinical and laboratory correlation of biomarkers with anti- and pro-apoptotic activity with the severity of motor and non-motor symptoms depending on the progression rate of Parkinson's disease (PD).MATERIAL AND METHODS:A wide range of non-motor symptoms (emotional-affective, cognitive, psychotic and behavioral disorders, fatigue, sleep disorders and autonomic disorders) was evaluated using validated scales and a number of serum neuromarkers responsible for neuroplasticity and neuronal survival processes (BDNF, PDGF, cathepsin D) in 71 patients with PD (mean age 65 (55; 70) years, disease duration 7 (4; 9) years, age of onset 57 (49; 62) years).RESULTS:The concentration of biomarkers (BDNF, PDGF and cathepsin D) was the lowest in the group of patients with a rapid PD progression rate (p<0.001, p=0.001 and p=0.031, respectively), the severity of motor and most non-motor symptoms was higher (p=0.023 and p=0.001, respectively) compared to middle and slow progression rate. There were correlations between BDNF concentration and the severity of depression (r=-0.63, p<0.001), apathy (r=-0.48, p<0.001), impulsive behavioral disorders (r=0.500, p<0.001), level of cognitive functions (r=0.54, p<0.001), motor symptoms (r=-0.43, p<0.001); between PDGF level and the severity of motor manifestations of PD (r=-0.30, p=0.011), depression (r=-0.70, p<0.001), apathy (r=-0.460, p<0.001), the degree of severity of behavioral disorders (r=0.742, p<0.001). No significant correlations were observed between the level of cathepsin D and the severity of clinical manifestations of PD, which indicates the connection of cathepsin D with the general pathogenesis of PD.CONCLUSION:The possibility of using serum proteins of the neurotrophin subfamily and the protein associated with autophagy, cathepsin D, as biomarkers that determine the prognosis of PD, is considered.

OBJECTIVE:To study the prevalence of chronic fatigue syndrome (CFS) and association of CFS with other clinical and neuropsychological manifestations of Parkinson's disease (PD) as well as with serum inflammatory markers and genetic polymorphisms. MATERIAL AND METHODS:The study included 533 patients with PD. All patients underwent clinical, neurological examination and neuropsychological testing using validated questionnaires: MoCA test, HADS, BDI-II, the Fatigue Severity Scale (FSS). Serum concentrations of inflammatory markers (slCAM-1, sVCAM-1, NCAM, CCL5, PAI-1 and MPO) were assessed in 144 patients using xMAP technology. A case-control study of CCL5 (rs2107538) and PAI-1 (rs2227631) gene polymorphisms was performed in connection with PD development and in groups differing in the presence/absence of CFS in PD. In addition, the relationship of these polymorphisms with variability in the levels of the corresponding proteins in the blood serum of patients was studied. Genotyping of CCL5 (rs2107538) and PAI-1 (rs2227631) polymorphisms was performed using real-time PCR with TaqMan probes. RESULTS:CFS is common in 66.7% of patients in the PD group. In addition, non-motor symptoms (emotional-affective, cognitive, autonomic disorders and pain) were more common in patients with CFS. A strong correlation has been established between the severity of CFS assessed with FSS and serum concentrations of CCL5, sVCAM-1, NCAM and slCAM-1. In newly diagnosed patients with PD who were not taking antiparkinsonian drugs at the time of the study and had CFS, higher correlations were noted between inflammatory markers and the severity of CFS manifestations. When comparing the distribution of genotypes and alleles of CCL5 (rs2107538) and PAI-1 (rs2227631) polymorphisms, some differences were found between the groups of patients with PD and controls (p<0.05). However, these polymorphisms did not affect the variability of serum protein levels CCL5 and PAI-1, respectively, nor did they affect the development of CFS in patients with PD. CONCLUSION:CFS is common in PD, and patients with PD and CFS are characterized by elevated levels of serum markers CCL5, sVCAM-1, slCAM-1 and NCAM, suggesting the importance of the inflammatory component in the development of neurodegenerative disease. In addition, the clinical course of PD in patients with CFS is aggravated by other non-motor manifestations, including emotional-affective, cognitive, autonomic disorders and pain. These results highlight the potential contribution of an inflammatory component to the development of fatigue associated with PD, starting from the earliest clinical stages of the disease.

The dopamine, serotonin and glutamate systems are jointly involved in the pathogenesis and pharmacotherapy of schizophrenia. We formulated a hypothesis that polymorphic variants of the GRIN2A, GRM3, and GRM7 genes may be associated with the development of hyperprolactinemia in patients with schizophrenia taking conventional and atypical antipsychotics as basic treatment. 432 Caucasian patients diagnosed with schizophrenia were examined. DNA was isolated from peripheral blood leukocytes using the standard phenol-chloroform method. For pilot genotyping, 12 SNPs in the GRIN2A gene, 4 SNPs in the GRM3 gene, and 6 SNPs in the GRM7 gene were selected. Allelic variants of the studied polymorphisms were determined by real-time PCR. The level of prolactin was determined by enzyme immunoassay. Among persons taking conventional antipsychotics, there were statistically significant differences in the distribution of genotype and allele frequencies in groups of patients with normal and elevated prolactin levels for the GRIN2A rs9989388 and GRIN2A rs7192557 polymorphic variants, as well as differences in serum prolactin levels depending on the genotype of the GRM7 rs3749380 polymorphic variant. Among persons taking atypical antipsychotics, statistically significant differences were found in the frequencies of genotypes and alleles of the GRM3 rs6465084 polymorphic variant. An association of polymorphic variants of the GRIN2A, GRM3, and GRM7 genes with the development of hyperprolactinemia in patients with schizophrenia taking conventional and atypical antipsychotics has been established for the first time. The identified associations of polymorphic variants of the GRIN2A, GRM3 and GRM7 genes with the development of hyperprolactinemia in patients with schizophrenia taking conventional and atypical antipsychotics have been established for the first time. These associations not only confirm the close connection of the dopaminergic, serotonergic, and glutamatergic systems in the development of schizophrenia, but also demonstrate the potential of taking into account the genetic component during therapy.

Background. Childhood obesity is one of the pressing problems in modern healthcare, since it is associated with a high risk of non-communicable diseases, such as bronchial asthma (BA).The aim. To determine the features of cytokine profiles in children with and without BA, depending on body weight and visceral fat area. Materials and methods. At the first stage, 506 Tomsk schoolchildren underwent anthropometry with the calculation of the body mass index (BMI) and measurement of the visceral fat area (VFA) using the InBody 770 analyzer. Fiftyone (51) children from the first stage were included in the second clinical and diagnostic stage. The children were divided into four clinical groups: "Obesity" (n = 17), "Visceral Obesity" (n = 7), "Asthma" (n = 15), and "Healthy Children" (n = 12). In all study participants, the levels of interleukin (IL)-6, IL-8, IL-4, IL-10, and immunoglobulin (Ig) E in the blood serum were determined by the multiplex assay (MagPix and Luminex 200 c analyzers). Statistical data analysis was carried out using the Statistica 10.0 software package and the 4.2.2 version of R.Results. The levels of IL-10 in the "Asthma" (p < 0.006) and "Obesity" (p < 0.008) groups were significantly higher than in the "Visceral Obesity" group. Significantly higher levels of IL-8 were found in patients with asthma (p < 0.003) and obesity (p < 0.003) compared to the "Visceral Obesity" group. Higher concentrations of IL-6 were found in the "Asthma" (p < 0.001) and "Obesity" (p < 0.028) groups compared to the "Visceral Obesity" group.Conclusion. Similar upward changes in IL-6, IL-8, and IL-10 in children with asthma and obesity without a history of asthma may explain the contribution of obesity to a risk of asthma in children, possibly through excessive production of these proinflammatory cytokines that contribute to the implementation of Th2-mediated allergic inflammation.

Background. Using external robotic tools in rehabilitation of patients after stroke could activate neuroplasticity mechanisms, thus reducing the ischemic area and improving the neurological outcome of the disease.Aim. To evaluate the effectiveness of early rehabilitation of stroke patients in Tomsk Regional Stroke Center using assistive robotic tools by correlational analysis of clinical and laboratory biomarkers of brain neuroplasticity.Materials and methods. The study included 68 patients who suffered from stroke of the middle cerebral artery. Early rehabilitation was carried out in Tomsk Regional Stroke Center using assistive robotic tools according to the protocol. Neurotrophic factors in blood serum were measured by the enzyme-linked immunosorbent assay. The severity of neurological disorders was characterized based on the Fugl – Meyer assessment scale (FMA).Results. The clinical effectiveness of early motor rehabilitation in Tomsk Regional Stroke Center is confirmed by the statistically significant increase on the FMA scale by 5.2 ± 2.4 points (p = 0.008). Positive association between neurotrophic factors in blood serum and FMA total score enables to consider the resulting data as an evidence of neuroplasticity activation associated with the use of robotic electromechanical technologies.

A comparative analysis of the level of neuroactive amino acidglutamate in the blood serum of 17 healthy individuals and 63patients with multiple sclerosis (MS), according to the course,stage and duration of the disease and disability, was performed.The level of glutamate was significantly higher in MSpatients (16.474.37 nmol/l) compared to healthyindividuals (11.313.08 nmol/l). It was increased by 43.4%in relapsing-remitting type of MS, by 45.3% in secondary progressiveMS, and by 66.3% in primary progressive MS. Inexacerbation of the disease, glutamate concentration reachedmaximum values (18.443.44 nmol/l) compared toremission (15.123.97 nmol/l). No significant changes inthe levels of glutamate depending on the duration of illnessand severity of disability were found. The obtained results canbe used as one of additional diagnostic criteria for determiningthe disease stage, and control over the level of glutamatemay become a new therapeutic target in MS.

OBJECTIVETo study the correlations between the level of antibodies to native and denatured DNA and psychopathological symptoms and illness duration in patients with schizophrenia.MATERIAL AND METHODSThe level of antibodies to native (double-stranded) DNA and denatured (single-stranded) DNA was studied in the serum of 50 patients with schizophrenia, including 12 patients with tardive dyskinesia (TD). The control group consisted of 30 people.RESULTSA significant twofold increase in antibodies to native DNA was detected in patients with TD. There was no correlation of the amount of antibodies to double-stranded DNA with the duration of disease and leading symptoms both between the groups of patients as well as in comparison with controls. A significant decrease in antibody levels to the denatured (single-stranded) DNA was found in schizophrenic patients compared to the control group (p=0.009). A significant decrease in the concentration of antibodies to single-stranded DNA in patients with increasing duration of the disease, as well as in patients with leading negative symptoms was revealed.CONCLUSIONThe results suggest that anti-DNAantibodies may not play a major role in the pathogenesis of schizophrenia.

The purpose of the present work was to study the clinical features and risk factors of tardive dyskinesia among the schizophrenia patients who durably receive the antipsychotic therapy. 180 of the 18 to 65 age bracket schizophrenia patients, who were treated in a residential psychiatric treatment facility, were examined with the use of the Positive and Negative Syndrome Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and the basic chart of formalized sociodemographic and clinico-dynamic features developed at the Tomsk Mental Health Research Institute. The acquired data were processed by the Mann–Whitney U-Test and χ2. The average age of the tardive dyskinesia patients turned out to be conclusively older than that of the patients without this derangement. People who have tardive dyskinesia statistically often happen to be single in comparison with other variants of marital status. It was found out that women happen to have tardive dyskinesia more often, which allows us to see the female gender as a risk factor. The tardive dyskinesia patients had certain negative symptoms. The patients were arranged into groups according to the prepotency of symptom-complexes over the subgroups: with orofacial, thoracolumbar and combined tardive dyskinesia. The average age of the orofacial dyskinesia patients turned out to be conclusively older than that of the patients without tardive dyskinesia. The negative symptoms level in the subgroup was conclusively higher than among those without tardive dyskinesia. The average age of the thoracolumbar dyskinesia patients was conclusively older than that of the patients without tardive dyskinesia. The average age of the combined dyskinesia patients was conclusively older than the patients without the tardive dyskinesia. The patients having schizophrenia for longer than 10 years prevailed in the combined dyskinesia group. Such characteristics as education level and social status, age of when the medical problem started, dominance of the positive symptoms, duration of antipsychotic agents administration, somatic condition, use of psychoactive substances, suicidal and hetero-aggressive behaviors make no contribution to the risk of tardive dyskinesia development in the presence of schizophrenia, and they are not protective factors either.

Glutamate is the major neurotransmitter with multiple functions in the central nervous system. Glutamate-mediated excitotoxicity is involved in the pathophysiological processes in schizophrenia. The purpose of this study was to determine the concentration of glutamate in the serum of patients with paranoid schizophrenia compared with healthy individuals, and depending on the duration of the schizophrenic process and leading clinical symptoms. We investigated the level of glutamate in the serum of 158 patients with paranoid schizophrenia and 94 healthy persons. Higher concentrations of glutamate in schizophrenic patients compared with healthy persons have been found. The maximum concentrations of glutamate were detected in patients with disease duration of more than ten years. Glutamate level in the serum does not depend on the prevailing negative or positive clinical symptoms. The increased concentration of glutamate can hypothetically contribute to dopaminergic and glutamatergic imbalance, leading to the development of psychotic symptoms and cognitive dysfunction.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that has been implicated in several biological processes in multiple tissues and cell types and acts as a ligand for five G-protein coupled receptors, generally referred to as S1P1–S1P5. FTY720 is a sphingosine analogue that, after phosphorylation by sphingosine kinases, binds to four of the five known S1P receptors. As an immunomodulatory drug, FTY720 is known to prevent lymphocyte egress through abrogation of S1P signaling via receptor internalization. Its clinical efficacy has been established in multiple sclerosis. In addition, an emerging body of experimental evidence points to potential direct effects on neurons, astrocytes, and glial cells. The effects of FTY720 on cells of the peripheral nerve, however, have not been investigated in vivo so far. To study the effects of FTY720 on peripheral nerve regeneration, we performed sciatic nerve crush in C57Bl/6 mice. Two weeks post-crush, we assessed sciatic nerve functionality by electrophysiology and walking track analysis, by histology the degree of myelination and axonal integrity. To better understand potentially relevantmechanisms we studied cAMP, a crucial factor for axonal regeneration, as well as oxidative stress, Clinical as well as electrophysiological measures indicated a significant improvement of axonal regeneration in FTY720-treated mice compared to control animals. Histology revealed a significantly increased thickness of myelin sheaths in crushed nerves of FTY720-treatedmice. In these nerves, cAMP levels were found to be increased, whereas dinitrophenyl-labeling of free protein carbonyls and visualization using HRP-DAB pointed to lower oxidative stress in FTY720-treated animals. Our data suggest that FTY720 may exhibit direct effects within the peripheral nervous system in vivo propagating peripheral nerve regeneration.