[Vitamin D and other indicators of calcium-phosphorus metabolism as possible predictors of Parkinson's disease]. / Vitamin D i drugie pokazateli kal'tsii-fosfornogo obmena kak vozmozhnye prediktory bolezni Parkinsona.

OBJECTIVE: To study a role of vitamin D and other indicators of calcium-phosphorus metabolism as possible predictors of Parkinson's disease (PD). MATERIAL AND METHODS: The main group consisted of 138 patients with PD, the control group included 79 patients without PD. Serum levels of 25-hydroxyvitamin D (25[OH]D) were determined by chemo-luminescence immunoassay. Additionally, the following biochemical markers were evaluated: parathyroid hormone, calcitonin, thyroid-stimulating hormone, thyroxine, alkaline phosphatase, inorganic phosphorus, total calcium, ionized calcium, total protein. In addition, densitometry of the spine (1-4 lumbar vertebrae), proximal femurs, and the middle third of the radius was performed. The relationship between the level of vitamin D in blood serum and clinical data was evaluated using correlation analysis. RESULTS: Regression analysis revealed a statistically significant contribution of the levels of parathyroid hormone, vitamin D, alkaline phosphatase and the T-value of the bone density of the neck of the right hip (T-score NRH) to the probability of PD. In the main group, bone mineral density was significantly different between the groups (p=0.028). Also, there was a high incidence of osteopenia (64%) and osteoporosis (73%). Based on the obtained regression equation, the probability of having PD is p=1/(1+exp2.673-0.007x-0.052y-0.037z-0.012k), where «x¼ is the parathyroid hormone level, «y¼ is T-score NRH, «z¼ is the vitamin D level, «k¼ is the activity of alkaline phosphatase, exp is the exponent. CONCLUSION: Vitamin D levels, alkaline phosphatase activity, and T-score NRH have a statistically significant effect on the likelihood of developing PD. With a decrease in the above indicators relative to normal values, the likelihood of having PD increases.

[The power exercises as a risk factor of Parkinson's disease]. / Silovaia fizicheskaia nagruzka kak faktor riska bolezni Parkinsona.

AIM: To study the relationship between the physical condition, degree of motor disturbances and power loading in former athletes with Parkinson's disease (PD). MATERIAL AND METHODS: The study included 20 men with PD, including 10 power athletes with training loads in the youth for more than 5 years and 10 non-athletic patients. A medical history of PD and accompanied hypertension were analyzed, body mass index and power hand index were measured and the orthostatic test from supine to sitting position was made. Motor function was assessed with the unified Parkinson's disease rating scale of the Movement Disorder Society (MDS UPDRS) - part III. RESULTS AND CONCLUSION: Former athletes with PD were younger compared to non-athletic patients (57.44±8,14 vs. 66.78±4.29 years; p<005) and had longer duration of the disease (6.56±5,36 vs. 3.60±3.50 years; p<0.05). The orthostatic reaction of the former athletes was accompanied by increasing of diastolic blood pressure (DBP), while there was a decrease in DBD in the non-athletic men. Hypokinetic syndrome was more pronounced in the former athletes. The slowing of movements (bradykinesia) were accessed as 3 points on MDS UPDRS in 6 people and 4 points in 4. The results show the impact of power training on the course and presentations of PD in former athletes.

[Parkinson disease and asthenic syndrome]. / Bolezn' Parkinsona i astenicheskii sindrom.

AIM: To study the clinical heterogeneity of fatigue syndrome and evaluate the efficacy of cytoflavin as an addition to standard treatment in patients with Parkinson's disease. MATERIAL AND METHODS: One hundred patients with Parkinson's disease and fatigue took part in the study, 59 patients continued to participate in the study including 59.3% (32) women and 40.7% (27) men. All patients received standard treatment. The equivalent daily dose of levodopa (LEDD) was 736.9±419.1 mg/day. The average age of patients was 67±8.6 (from 65 to 85 years). Cytoflavin was used as an additional therapy in the standard dosage. All patients underwent neuropsychological examination for an estimate of the rate of fatigue, depression, health status, activity, mood and quality of life. RESULTS AND CONCLUSION: Cytoflavin is well tolerated by patients with Parkinson's disease and fatigue syndrome at the standard dosage. It improves the health, mood, quality of life and reduces fatigue.

[Parkinson's disease and glutamate excitotoxicity]. / Bolezn' Parkinsona i glutamatnaia éksaitotoksichnost'.

AIM: To measure the concentration of glutamate in the serum of patients with Parkinson's disease (PD) and determine its association with clinical variants of disease course. MATERIAL AND METHODS: One hundred and ten patients with PD and 90 healthy people were examined. Glutamate concentration in the blood serum was determined with a spectrophotometric method. RESULTS AND CONCLUSION: Patients with Parkinson's disease had significantly higher levels of serum glutamate compared with healthy subjects (p<0,0001). Patients with a tremor-dominant subtype had significantly higher levels of serum glutamate compared to those in patients with akinetic-rigid and mixed subtypes. The results obtained allow us to expand our understanding of the pathogenesis of this disease. Changes in the concentration of glutamate may reflect neurodegenerative process in PD.

[Possibilities of retention of work capacity in patients with Parkinson's disease]. / Vozmozhnosti sokhraneniia trudosposobnosti u patsientov s bolezn'iu Parkinsona.

AIM: To study the efficacy of replacement of the single daily dose of two-component levodopa by three-component levodopa in work capable patients with Parkinson's disease with motor fluctuations during the most active working hours. MATERIAL AND METHODS: The study included 157 patients from 19 Russian centers specialized in extrapyramidal pathology. The period of highest working activity was analyzed in all patients. In these patients, the previous treatment with two-component levodopa was replaced by three-component levodopa in the equivalent dose. Other antiparkinsonian treatment remained unchanged during the study period. The duration of the study was 1 month. RESULTS AND CONCLUSION: The single replacement of two-component levodopa by stalevo allows increasing the optimal working activity by 19% and improving patient's state.

[A rare variant in the sortilin-related receptor 1 gene is associated with declined cognitive functions in the elderly]. / Redkii variant v gene sortilinpodobnogo retseptora 1: sviaz' s pokazateliami kognitivnykh funktsii u pozhilykh.

AIM: To estimate the association of rs11218343 in the sortilin-related receptor 1 (SORL1) gene with cognitive performance in the elderly and with Alzheimer's disease (AD) in the Russian population. MATERIAL AND METHODS: A sample included 586 elderly people (mean age 70.9±5.7 years) without AD diagnosis and 100 patients with late-onset AD (mean age 72.1±7.8 years) from the Tomsk population. SORL1 rs11218343 was genotyped using PCR and MALDI-TOF mass spectrometry. Cognitive performance in the sample of elderly without AD was assessed by Montreal Cognitive Assessment (MoCA) test. RESULTS: Allele frequencies of the SORL1 polymorphism were not significantly different between the elderly without AD and AD patients. However mean MoCA score in the carriers of the rare allele (19.00±6.61) was significantly lower than in homozygotes for the common variant (22.25±3.89) (F=4.97; p=0.026). CONCLUSION: The rare variant in SORL1 gene previously associated with AD in genome-wide association studies and meta-analyses was associated with lower total МоСА scores in the random sample of elderly people that suggests declined cognitive functions in the carriers of this variant in elderly.

[Parkinson's disease and glutamatergic system]. / Bolezn' Parkinsona i glutamatergicheskaia sistema.

Clinical variants of Parkinson's disease (PD) are not restricted to motor symptoms but include a wide spectrum of different non-motor symptoms: cognitive, psychotic, autonomic and sensory. These non-motor symptoms often occur long before classical motor features. Associated pathologic changes can now be identified at earliest stages using neuroimaging, pathomorphological and genetic studies. Therefore, PD is currently considered as a multifactorial, heterogenic systemic disease associated with involvement of multiple neurotransmitter systems. This leads to understanding that not only dopaminergic but also other neurotransmitter systems, including glutamatergic system, are involved in the pathogenesis of PD. This article aimed at investigating a role of glutamatergic system in the initiation of neurodegenerative process. The role of glutamate as a neurotransmitter and a neurotoxin in the pathogenesis of PD and progression of its clinical manifestations is discussed. The authors suggest that research into glutamate excitotoxicity in PD patients might allow the improvement of treatment tactics and correction of pathogenetic therapy.

Analysis of Gut Microbiota in Patients with Parkinson's Disease.

Gut microbiota of patients with Parkinson's disease and healthy volunteers was analyzed by the method of high throughput 16S rRNA sequencing of bacterial genomes. In patients with Parkinson's diseases, changes in the content of 9 genera and 15 species of microorganisms were revealed: reduced content of Dorea, Bacteroides, Prevotella, Faecalibacterium, Bacteroides massiliensis, Stoquefichus massiliensis, Bacteroides coprocola, Blautia glucerasea, Dorea longicatena, Bacteroides dorei, Bacteroides plebeus, Prevotella copri, Coprococcus eutactus, and Ruminococcus callidus, and increased content of Christensenella, Catabacter, Lactobacillus, Oscillospira, Bifidobacterium, Christensenella minuta, Catabacter hongkongensis, Lactobacillus mucosae, Ruminococcus bromii, and Papillibacter cinnamivorans. This microbiological pattern of gut microflora can trigger local inflammation followed by aggregation of α-synuclein and generation of Lewy bodies.

A Method for Quantitative Evaluation of the Results of Postural Tests.

A method for quantitative evaluation of the results of postural tests is proposed. The method is based on contact-free measurements of 3D coordinates of body point movements. The result can serve as an integral test based on the Mahalanobis distance.

[The association of the DRD3 gene with Parkinson's disease].

OBJECTIVE: To investigate the association between dopamine receptor DRD3 gene tag single nucleotide polymorphisms (SNPs) and the risk of Parkinson's disease (PD). MATERIAL AND METHODS: One hundred and forty-three patients with PD and 96 healthy individuals from the Russian population were examined. Ten tag SNPs (rs963468, rs2134655, rs9817063, rs324035, rs11721264, rs1800828, rs3773678, rs167770, rs167771, rs7633291) within DRD3 have been genotyped. RESULTS AND CONCLUSION: Associations between 4 polymorphisms (rs11721264, rs3773678, rs167771, rs324035) and PD have been found. Our study confirms the involvement of polymorphic features of dopamine receptors genes in the pathophysiology in PD.

[A role of the gastrointestinal tract microbiota in the pathogenesis of Parkinson's disease]. / Vozmozhnaia rol' mikrobioty zheludochno-kishechnogotraktavpatogenezebolezniarkinsona.

Microbiota is a community of microorganisms, viruses, protozoa, colonizing the gut. There are tight phylogenetic relationships between the gut microbiota and the human body, the disturbance of which may lead to the CNS dysfunction as well as to the development of neurodegenerative diseases. This review focuses on general and specific aspects of the influence of gut microbiota on the pathogenesis of Parkinson's disease (PD). Current theories and models of the relationship between microbiota and brain structures in PD are presented with a specific focus on neurochemical and immunological aspects of the problem.

[Correlation Between Emotional-Affective Disorders and Gut Microbiota Composition in Patients with Parkinson's Disease].

Background: Despite the efforts of scientific community the data available on the correlation between emotional-affective symptoms of Parkinson's disease and changes in microbiome is still scarce. Deeper studies of nonmotor symptoms evident in premotor stages of the disease and the reciprocal influence of microbiota may help to understand the etiology and pathogenesis of PD neurodegeneration better. Aim of the Study: Discover the relations between emotional-affective disorders prevalent in PD population and changes in gut microbiota composition. Methods: 51 patient diagnosed with PD participated in the study. Every participant's emotional-affective state was examined using Beck's Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS). Taxonomic richness of microbiome was studied using 16S ribosomal RNA gene sequencing, bioinformatics, and statistical analysis. Results: Anxiety and depression are prevalent affective disorders in patients with PD. In our study, most of the subjects demonstrated certain anxiety and depression. Taxonomic diversity of gut microbiota in BP was increasing with the increase in anxiety levels, reaching the maximum in the group with subclinical anxiety, and decreasing in the group with clinically significant anxiety disorder. At the species level, patients with clinically significant anxiety had higher abundance of Clostridium clariflavum compared to the anxiety-free patients. Patients with moderate depression were characterized by the higher prevalence of Christensenella minuta, Clostridium disporicum, and Oscillibacter valericigenes compared to subjects without depression or with mild depression. Conclusion: The data we received in our study allow better understanding of PD pathogenesis.

[Methods for evaluating of olfactory function in patients with Parkinson's disease]. / Analiz metodov otsenki obonianiia u patsientov s bolezn'iu Parkinsona.

Olfactory disorder takes a special place among non-motor symptoms of Parkinson's disease (PD) as one of earliest signs of the disease. Based on literature data, authors suggest that simple and structured tests for detection of olfactory disorders should be part of diagnostic algorithm for early detection of PD) and occupy a special place in differential diagnosis of diseases of the extrapyramidal system. Literature on the methods of study of olfactory function recommended as an additional instrument for PD diagnosis is presented.

[Replicative association analysis of genetic markers of cognitive traits with Alzheimer's disease in a Russian population].

Replicative association analysis of Alzheimer's disease (AD) with 15 genetic markers associated with cognitive traits in genome-wide association studies was performed. In a Russian populations associations of rs2616984 in CSMD1 gene with AD (OR = 1.50, 95% CI = 1.07-2.09, p-value = 0.018) and putative associations with the disease of rs3131296 in NOTCH4 gene (OR = 1.53, 95% CI = 0.98-2.39, p-value = 0.06) and rs2229741 of NRIP1 gene (OR = 1.35, CI = 0.99-1.85, p-value = 0.061) were revealed. Combinations of epistatic interacting genes (CSMD1 and NRIP1; NOTCH4, CSMD1 and NRIP1; TLR4, CSMD1 and NRIP1) were found, as well as their genotypes combinations significantly associated with AD and characterized by highest predictive values. Probable molecular mechanisms implicated in the relation of genes under study to AD pathogenesis are discussed. Bioinformatic analysis of biological processes, molecular functions and protein-protein interactions of BA genes demonstrated that genes under study may play modulating and modifying role by participation in various regulatory and signal pathways involved in a disease development.

[Preclinical study of anxiolytic activity and safety of Racium phytomedicine].

Results of a preclinical study of the anxiolytic activity and safety of original Racium phytomedicine are presented. The preparation possessed high anxiolytic activity, exhibits a wide range of therapeutic effects, produces no lethality in male and female rats and mice upon single intragastric and intraperitoneal introduction in doses up to 5 g/kg (VI class of toxicity according to OECD), induces no pathologic effects upon prolonged (120 days) administration in these rodents, and has no local irritant and/or allergen action.

NMDA receptor genotypes associated with the vulnerability to develop dyskinesia.

Dyskinesias are involuntary muscle movements that occur spontaneously in Huntington's disease (HD) and after long-term treatments for Parkinson's disease (levodopa-induced dyskinesia; LID) or for schizophrenia (tardive dyskinesia, TD). Previous studies suggested that dyskinesias in these three conditions originate from different neuronal pathways that converge on overstimulation of the motor cortex. We hypothesized that the same variants of the N-methyl-D-aspartate receptor gene that were previously associated with the age of dyskinesia onset in HD were also associated with the vulnerability for TD and not LID. Genotyping patients with LID and TD revealed, however, that these two variants were dose-dependently associated with susceptibility to LID, but not TD. This suggested that LID, TD and HD might arise from the same neuronal pathways, but TD results from a different mechanism.

Nanocomposites based on poly-D,L-lactide and multiwall carbon nanotubes.

A possibility of poly-D,L-lactide modification by multiwall carbon nanotubes (MWCNT) has been shown. MWCNT were prepared from methane-air mixture upon atmospheric pressure without catalyst on high voltage atmospheric pressure discharge plasma set-up. According to scanning and transmission electronic microscope data carbon nanotubes diameters were within 12-60 nm. Quantities of MWCNT incorporated did not exceed 0.5%. Nanocomposites were obtained by sonification of mixture of a poly-D,L-lactide solution in chloroform and MWCNT followed by film casting on glass substrates. Tensile strength and thermomechanical properties of the dried composite films were investigated. Introduction of MWCNT into poly-D,L-lactide has been shown to cause the enhanced polymer stability to thermal oxidative destruction. Taking into account the results obtained one could anticipate that implants from nanocomposites of poly-D,L-lactide with MWCNT would be dispersed in a living organism more slowly as compared to implants from pure poly-D,L-lactide without additives.