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OBJECTIVE: To evaluate the frequency and severity of various clinical symptoms of Parkinson's disease (PD) depending on the BDNF rs6265 polymorphism. MATERIAL AND METHODS: The study included 533 patients with PD. The stage of PD was assessed using the Hoehn and Yahr scale (1967), motor symptoms were evaluated with MDS-UPDRS. Assessment of non-motor symptoms (NMS) in PD was conducted using the Beck Depression Inventory II (BDI-II); the Hospital Anxiety and Depression Scale (HADS); the Apathy Scale; the Montreal Cognitive Assessment (MoCA test); the Questionnaire for Impulsive-Compulsive Disorders in PD -Rating Scale (QUIP-RS). Genotyping of the BDNF variant (rs6265) was performed using real-time PCR with TaqMan probes. RESULTS: Most PD patients have a combination of NMS increasing as the disease progresses and is determined by molecular-genetic individual characteristics. There are significant differences in the severity of motor symptoms and NMS: individuals with the AA genotype showed significantly pronounced motor symptoms (p<0.0001); emotional-affective symptoms (p<0.0001); cognitive and impulsive behavioral disorders (p<0.0001). CONCLUSION: The rs6265 BDNF allele A is associated with a wide range of NMS, increasing the risk of their development in patients with PD, thus playing the important role in the etiopathogenesis of this pathology.
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Factor Neurotrófico Derivado del Encéfalo , Enfermedad de Parkinson , Polimorfismo de Nucleótido Simple , Humanos , Factor Neurotrófico Derivado del Encéfalo/genética , Enfermedad de Parkinson/genética , Femenino , Masculino , Persona de Mediana Edad , Anciano , Genotipo , Índice de Severidad de la Enfermedad , Depresión/genéticaRESUMEN
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.
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Biomarcadores , Factor Neurotrófico Derivado del Encéfalo , Catepsina D , Progresión de la Enfermedad , Enfermedad de Parkinson , Factor de Crecimiento Derivado de Plaquetas , Humanos , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Catepsina D/sangre , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Factor de Crecimiento Derivado de Plaquetas/análisis , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To evaluate the clinical features and the level of serum brain-derived neurotrophic factor (BDNF) in groups of patients with Parkinson's disease (PD) differentiated by the genotypes of BDNF polymorphism (rs6265). MATERIAL AND METHODS: The level of serum BDNF in the biomarkers' multiplex panel of neurodegenerative diseases (HNDG3MAG-36K) was assessed in 134 PD patients. Allele discrimination was carried out by real-time PCR using TaqMan probes for the analysis of BDNF rs6265 polymorphism in groups of patients and controls (n=192) matched for sex, age and ethnicity. RESULTS: Comparing the distribution of rs6265 genotypes and alleles between groups of patients and controls no significant differences were found (p>0.05). Serum BDNF levels varied significantly by genotype (rs6265) among PD patients. Minimum mean serum BDNF level (320.1±164.6 pg/ml) was noted for individuals with the AA genotype, which significantly differs from the corresponding indicator among individuals with GA (2944.2±1590.6 pg/ml; p=0.0001) and GG genotypes (2949.4±1620.6 pg/ml; p=3.9×10-5). The concentration of BDNF significantly differed between patients with different forms of PD (p=0.0007) and increased as the stage of the disease progressed according to Hoehn and Yahr staging scale (p=1.0×10-6). CONCLUSION: The BDNF rs6265 polymorphism was not associated with the development of PD in the studied population. The variability of the mean serum BDNF level was established depending on the genotype of the BDNF polymorphism in PD patients and a number of clinical features.
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Factor Neurotrófico Derivado del Encéfalo , Enfermedad de Parkinson , Humanos , Alelos , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/genética , Etnicidad , Genotipo , Enfermedad de Parkinson/genéticaRESUMEN
Mild encephalopathy with a reversible splenial lesion (MERS) is a clinical and radiological syndrome that can be caused by infectious and non-infectious factors. The most common neurological symptoms are impaired consciousness, impaired speech, convulsions, muscle weakness, ophthalmoplegia, facial paralysis, and headache. A case of a 5-year-old child with a leading clinical symptom of bilateral transient blindness and radiological characteristics of MERS syndrome is presented.
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Encefalopatías , Cuerpo Calloso , Encefalopatías/diagnóstico , Preescolar , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Cefalea/patología , Humanos , Imagen por Resonancia Magnética , SíndromeRESUMEN
Genetic factors underlie the pathological processes that cause the manifestation of a wide range of neurodegenerative diseases. The pathological expansion of unstable trinucleotide repeats is known to lead monogenic neurological diseases such as Huntington's disease, Kennedy's disease, spinocerebellar ataxia, and others. However, the latest data suggests individuals with intermediate allele (IA) repeat length have a risk of developing common neurological phenotype, for example, Parkinson's disease, Alzheimer's disease. In this study, we review the current knowledge on intermediate alleles of HTT gene for pathogenesis and clinical features of neurodegenerative diseases, with the focus on Parkinson's disease. Early diagnosis of neurodegenerative disease and genetic counselling of the family can be improved via the implementation of specific management strategies of IA carriers by team of highly experienced professionals in the fields of neurology and genetics.
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Enfermedad de Huntington , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Alelos , Humanos , Proteína Huntingtina/genética , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/genética , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/genética , Enfermedad de Parkinson/genética , Expansión de Repetición de Trinucleótido , Repeticiones de Trinucleótidos/genéticaRESUMEN
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.
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Microbioma Gastrointestinal/genética , Bacterias Gramnegativas/genética , Bacterias Grampositivas/genética , Enfermedad de Parkinson/microbiología , Filogenia , ARN Ribosómico 16S/genética , Anciano , Biodiversidad , Estudios de Casos y Controles , Código de Barras del ADN Taxonómico/métodos , ADN Bacteriano/genética , Heces/microbiología , Femenino , Bacterias Gramnegativas/clasificación , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/clasificación , Bacterias Grampositivas/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Análisis de Secuencia de ADNRESUMEN
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.
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Ansiedad , Depresión , Microbioma Gastrointestinal/genética , Enfermedad de Parkinson , Anciano , Ansiedad/diagnóstico , Ansiedad/fisiopatología , Depresión/diagnóstico , Depresión/fisiopatología , Femenino , Tracto Gastrointestinal/microbiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/microbiología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Escalas de Valoración Psiquiátrica , ARN Ribosómico 16S/análisis , Análisis de Secuencia , Estadística como AsuntoRESUMEN
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.
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Microbioma Gastrointestinal , Enfermedad de Parkinson/microbiología , Encéfalo , Tracto Gastrointestinal , Humanos , Microbiota , FilogeniaRESUMEN
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.
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Universal values of dimensional effective coupling constants g(2k) that determine nonlinear susceptibilities χ(2k) and enter the scaling equation of state are calculated for n-vector field theory within the pseudo-ε expansion approach. Pseudo-ε expansions for g(6) and g(8) at criticality are derived for arbitrary n. Analogous series for ratios R(6) = g(6)/g(4)(2) and R(8) = g(8)/g(4)(3) that figure in the equation of state are also found, and the pseudo-ε expansion for Wilson fixed point location g(4)(*) descending from the six-loop renormalization group (RG) expansion for the ß function is reported. Numerical results are presented for 0 ≤ n ≤ 64, with the most attention paid to the physically important cases n = 0,1,2,3. Pseudo-ε expansions for quartic and sextic couplings have rapidly diminishing coefficients, so Padé resummation turns out to be sufficient to yield high-precision numerical estimates. Moreover, direct summation of these series with optimal truncation gives values of g(4)(*) and R(6)(*) that are almost as accurate as those provided by the Padé technique. Pseudo-ε expansion estimates for g(8)(*) and R(8)(*) are found to be much worse than those for lower-order couplings independently of the resummation method employed. The numerical effectiveness of the pseudo-ε expansion approach in two dimensions is also studied. Pseudo-ε expansion for g(4)(*) originating from the five-loop RG series for the ß function of two-dimensional λÏ(4) field theory is used to get numerical estimates for n ranging from 0 to 64. The approach discussed gives accurate enough values of g(4)(*) down to n = 2 and leads to fair estimates for Ising and polymer (n = 0) models.
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The critical exponent η for three-dimensional systems with an n-vector order parameter is evaluated in the framework of the pseudo-ε expansion approach. The pseudo-ε expansion (τ series) for η found up to the τ(7) term for n = 0, 1, 2, 3 and within the τ(6) order for general n is shown to have a structure that is rather favorable for getting numerical estimates. The use of Padé approximants and direct summation of the τ series result in iteration procedures rapidly converging to the asymptotic values that are very close to the most reliable numerical estimates of η known today. The origin of such an efficiency is discussed and shown to lie in the general properties of the pseudo-ε expansion machinery interfering with some peculiarities of the renormalization group expansion of η.
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Modelos Teóricos , TemperaturaRESUMEN
The critical behavior of two-dimensional n-vector λÏ4 field model is studied within the framework of pseudo-ε expansion approach. Pseudo-ε expansions for Wilson fixed-point location g* and critical exponents originating from five-loop two-dimensional renormalization-group series are derived. Numerical estimates obtained within Padé and Padé-Borel resummation procedures as well as by direct summation are presented for n=1, n=0, and n=-1, i.e., for the models which are exactly solvable. The pseudo-ε expansions for g*, critical exponents γ, and ν have small lower-order coefficients and slow increasing higher-order ones. As a result, direct summation of these series with optimal cutoff provides numerical estimates that are no worse than those given by the resummation approaches mentioned. This enables one to consider the pseudo-ε expansion technique itself as some specific resummation method.
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In September-December 1998 the epidemic rise of outhospital pneumonia (EP) among children was observed in St. Petersburg, which led to a twofold increase in morbidity rate this year. The study of the etiology of EP during the period of 1998-2001 confirmed the prime role of Streptococcus pneumoniae (74.5%) and, for the first time in Russia, revealed the epidemic outbreak of acute chlamydiosis (Chlamydia pneumoniae), diagnosed in 67.3% of children, the maximum occurrence (87.5%) in 1998 with only 19% of the patients having the disease in the form of monoinfection. The prevalence of S. pneumoniae and C. pneumoniae in the etiology of EP and more severe course of mixed infection suggested that these infective agents played a leading role in the epidemic outbreak of acute respiratory infections in St. Petersburg.
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Infecciones por Chlamydophila/epidemiología , Brotes de Enfermedades , Neumonía Bacteriana/epidemiología , Adolescente , Anticuerpos Antibacterianos/sangre , Niño , Preescolar , Infecciones por Chlamydophila/sangre , Infecciones por Chlamydophila/microbiología , Chlamydophila pneumoniae/inmunología , Chlamydophila pneumoniae/aislamiento & purificación , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Comorbilidad , Hospitales Comunitarios , Humanos , Lactante , Neumonía Bacteriana/sangre , Neumonía Bacteriana/microbiología , Neumonía Neumocócica/sangre , Neumonía Neumocócica/epidemiología , Neumonía Neumocócica/microbiología , Prevalencia , Federación de Rusia/epidemiología , Estudios Seroepidemiológicos , Streptococcus pneumoniae/inmunología , Streptococcus pneumoniae/aislamiento & purificación , Población UrbanaRESUMEN
The dynamics of the antibody formation to S. pneumoniae and C. pneumoniae in children during the epidemic outbreak of non-hospital pneumonia in St. Petersburg in 1998-2001 was studied. For the first time the inhibiting influence of acute C. pneumoniae infection on the synthesis of antibodies to S. pneumoniae in acute mixed infection was established. The prolonged (up to days 29-39 of the disease) circulation of IgM and IgG antibodies in acute chlamydial infection, as well as the prevalence of the primary infectious process, were detected.
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Anticuerpos Antibacterianos/sangre , Infecciones por Chlamydia/diagnóstico , Chlamydophila pneumoniae/inmunología , Neumonía Bacteriana/diagnóstico , Neumonía Neumocócica/diagnóstico , Streptococcus pneumoniae/inmunología , Enfermedad Aguda , Adolescente , Anticuerpos Antibacterianos/biosíntesis , Niño , Preescolar , Infecciones por Chlamydia/sangre , Infecciones por Chlamydia/epidemiología , Comorbilidad , Factores de Confusión Epidemiológicos , Brotes de Enfermedades , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lactante , Neumonía Bacteriana/sangre , Neumonía Bacteriana/epidemiología , Neumonía Neumocócica/sangre , Neumonía Neumocócica/epidemiología , Federación de Rusia/epidemiología , Estudios Seroepidemiológicos , Población UrbanaRESUMEN
General characteristics of nucleoli in all layers of stratified squamous epithelium were studied in 234 cases of dysplasia and intraepithelial cancer of cervix uteri. Cytomorphometric measurements were carried out. The nuclear-cytoplasmic ratio was determined. Certain regularities pertinent to neoplastic process progression and aging were established. 2,375 patients with moderate dysplasia and 1,625 patients with marked dysplasia underwent clinical examination. Various schemes of treatment and long-term results were evaluated. Rationale for all-round examination and individually-tailored schemes of treatment is discussed. The data on the end results in 150 untreated cases of dysplasia are presented. The importance of detection and treatment of dysplasia in the control of cervical cancer is suggested.