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Anthropometric studies conducted in 1884, 1928, 1946, 1965 and 1999 to study the characteristics of growth and weight indicators of children living in the territory of modern Chuvashia, partly reflected the influence of the living conditions of children in certain historical periods of the country's development: revolutions, civil and domestic wars, post-war stabilization, «perestroika¼. Over the last 22-year period, from 1999 to 2021, there has been the largest increase in the growth rate of indicators of the physical development of children and adolescents, which is considered as a positive trend, a manifestation of ongoing acceleration processes. It was revealed that in modern children, physiological growth jumps in comparison with their peers in 1884, 1930, and 1999 occur earlier - in the prepubertal period.
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The need to preserve and promote health of children determine one of the basic directions of development of public social policy. It is the most important strategic purpose of modern children health care, since from it depend health of the nation, increasing of life expectancy and national economic potential.Purpose of the study is to assess health status of children of adolescent age born at term with diagnosis "fetus with low birth weight for gestational age" and with large body mass. The bibliographic, information-analytical and comparative analysis methodology were applied.
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Tamanho Corporal , Nível de Saúde , Recém-Nascido Pequeno para a Idade Gestacional , Adolescente , Criança , HumanosRESUMO
Changes in metabolic pathways are often associated with the development of a wide range of pathologies. Increased glycolysis under conditions of sufficient tissue oxygen supply and its dissociation from the Krebs cycle, known as aerobic glycolysis or the Warburg effect, is a hallmark of many malignant neoplasms. Identification of specific metabolic shifts can characterize the metabolic programming of individual types of tumor cells, the stage of their transformation, and predict their metastatic potential. Viral infection can also alter the metabolism of cells to support the process of viral replication. Infection with human immunodeficiency virus type 1 (HIV-1) is associated with an increased incidence of various cancers, and for some viral proteins a direct oncogenic effect was demonstrated. In particular, we showed that the expression of HIV-1 reverse transcriptase (RT) in 4T1 breast adenocarcinoma cells increases the tumorigenic and metastatic potential of cells in vitro and in vivo by a mechanism associated with the ability of RT to induce reactive oxygen species in cells (ROS). The aim of this work was to study the molecular mechanism of this process, namely the effect of HIV-1 RT on the key metabolic pathways associated with tumor progression: glycolysis and mitochondrial respiration. Expression of HIV-1 RT had no effect on the glycolysis process. At the same time, it led to an increase in mitochondrial respiration and the level of ATP synthesis in the cell, while not affecting the availability of the substrates, carbon donors for the Krebs cycle, which excludes the effect of RT on the metabolic enzymes of cells. Increased mitochondrial respiration was associated with restoration of the mitochondrial network despite the RT-induced reduction in mitochondrial mass. Increased mitochondrial respiration may increase cell motility, which explains their increased tumorigenicity and metastatic potential. These data are important for understanding the pathogenesis of HIV-1 infection, including the stimulation of the formation and spread of HIV-1 associated malignancies.
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Neoplasias da Mama , Carcinogênese , Transcriptase Reversa do HIV , HIV-1 , Mitocôndrias , Trifosfato de Adenosina/biossíntese , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/virologia , Carbono/metabolismo , Carcinogênese/genética , Linhagem Celular Tumoral , Respiração Celular , Ciclo do Ácido Cítrico , Feminino , Transcriptase Reversa do HIV/genética , HIV-1/genética , HIV-1/metabolismo , Camundongos , Mitocôndrias/metabolismo , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Aim to identify outdated terms and make changes to the terminology of spondyloarthritis. MATERIALS AND METHODS: At the first stage of the work, the terms divided into two categories: "outdated" definitions and terms that need to be improved or unified. Subsequently, each member of the Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia (ExSpA) presented by its own definition of the designated term or agreed with the previous term. At the next stage, the existing definitions were put together. After discussion, experts left a term that scored at least 2/3 of the votes. The special opinion of experts was recorded, whose did not coincide with the majority opinion. An open vote was conducted, when defining an "outdated" term with the unanimous decision of all group members, this term was not recommended for further clinical use. RESULTS: The work carried out allowed us to identify a number of terms that are not recommended for use in clinical practice. Number of terms are defined, which should be used when discussing the problem of spondyloarthritis. CONCLUSION: The Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia suggests using or, accordingly, not using a number of terms and their definitions in clinical practice.
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Espondilartrite , Humanos , Federação Russa , Espondilartrite/diagnóstico , Terminologia como AssuntoRESUMO
AIM: To consider association of chronic adrenal insufficiency in patients with APS of adults with polymorphism of class II HLA genes, -CTLA-4 and PTPN-22. MATERIALS AND METHODS: The case-control study involved 78 patients with APS 2, 3, 4 types and 109 healthy subjects). Alleles of the HLA class II genes, CTLA-4 and PTPN-22 were identified by the multiprimer allele-specific PCR method. The statistical analysis was carried out using the exact two-sided Fisher test. The association of the chronic adrenal insufficiency in patients with APS was determined by the value of the odds ratio (OR - odd's ratio), the value of 95% confidence interval (95% CI - confidence interval). RESULTS: Haplotypes DR3-DQ2 (OR = 4.06), DR4-DQ8 (OR = 5.78), genotype DR3/DR4 (OR = 19.7), DQA1 * 0301 allele (OR = 4.27), as well as genotype DQA1 * 0301 / DQA1 * 0501 (OR = 13.89) predispose to the development of APS of adults compared to the control group. APS patients were divided into two groups according to the presence of chronic adrenal insufficiency (APS 2 and 4 types - in one group and type 3 APS in the other group). Haplotype DR3-DQ2 (DRB1 * 17-DQA1 * 0501 -DQB1 * 0201) (OR = 2.6), as well as the genotype DR3/DR4 (OR = 4.28) found the strongest association with the development of adrenal insufficiency in patients with APS of adults. Protective haplotypes DRB1 * 01-DQA1 * 0101-DQB1 * 0501 (p<0.01, OR = 0.07), as well as the DRB1 * 01 allele (p<0.01, OR = 0.08) have been identified with respect to the development of adrenal insufficiency in adult APS patients. CONCLUSION: Examination of patients with APS of adults without chronic adrenal insufficiency for the presence of protective genes for the development of adrenal insufficiency will allow better predicting the risks of developing of the disease within the syndrome.
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Insuficiência Adrenal , Doenças Autoimunes , Diabetes Mellitus Tipo 1 , Genes MHC da Classe II , Insuficiência Adrenal/etiologia , Adulto , Alelos , Doenças Autoimunes/complicações , Doenças Autoimunes/genética , Estudos de Casos e Controles , Frequência do Gene , Genes MHC da Classe II/genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , SíndromeRESUMO
AIM: To identify factors affecting the effectiveness of NSAIDs in patients with OA and LBP. MATERIALS AND METHODS: An observational study was conducted to evaluate the effectiveness of a 2-week course of NSAIDs in OA and LBP in real clinical practice. The study group consisted of 3604 patients with OA and LBP (60.6% women and 39.4% men, mean age 55.0±13.4 years). According to the study design, aceclofenac (Airtal) and other NSAIDs used in the ratio 1:1. The main criterion of effectiveness was the frequency of complete pain relief after 2 weeks of therapy. In addition, the decrease of pain and general health were determined on a 10-point numerical rating scale (NRS). We compared the frequency of complete pain relief in patients who had and did not have the studied factors. The value of the studied factors was determined using OR (95% CI). RESULTS: Most patients received aceclofenac (54.9%), as well as diclofenac (2.0%), ketoprofen (1.9%), lornoxicam (2.2%), meloxicam (13.7%), naproxen (2.1%), nimesulide (5.8%), celecoxib (5.9%), ethicoxib (7.1%) and other NSAIDs (4.4%); 56.2% of patients received muscle relaxants, mainly tolperisone (74.7%), vitamin B (10.4%), and proton pump inhibitors (42.8%). Complete pain relief was achieved in 54.8% of patients. The pain decrease and general health improvement were (for NRS) 63.9±13.4% and 61.7±14.8%, respectively. The efficacy of aceclofenac was slightly higher than in the whole group: complete pain relief was in 59.9% of patients. Adverse events in aceclofenac use were observed in 2.3% of patients, other NSAIDs-from 2.4 to 14.1%. The frequency of complete pain relief was higher in men: OR 1,239 (95% CI 1.08-1.418; p=0.002), who had the first episode of pain - OR 3.341 (95% CI 2.873-3.875; p=0.000), a good" response " to NSAIDs in history - OR 1.656 (95% CI 1.385-1.980; p=0.000) and received NSAIDs in combination with muscle relaxants - OR 1.218 (95% CI 1.067-1.390; p=0.004). The effect of therapy is lower in patients 65 years and older-OR 0,378 (95% CI 0.324-0.442; p=0,000), with body mass index >30 kg/m² - OR 0.619 (95% CI 0.529-0.723; p=0.000), with severe pain (≥7 points NRS) - OR 0.662 (95% CI 0.580-0.756; p=0.002), with pain at rest, - OR 0.515 (95% CI 0.450-0,589; p=0.000), pain at night - OR 0.581 (95% CI 0.501-0.672; p=0.000) and the presence of stiffness - OR 0.501 (95% CI 0.438-0,573; p=0.000). Treatment results are significantly worse in the cases of combination of LBP and joint pain, as well as pain in the trochanter major and pes anserinus area (p<0.001). CONCLUSION: NSAIDs are the first-line medications for the pain treatment in LBP and OA. Aceclofenac is effective and safe in this conditions. When carrying out analgesic therapy should take into account factors that affect the effectiveness of treatment: old age, overweight, insufficient effect of NSAIDs in history, severe pain, signs of "inflammatory" pain, multiple sources of pain.
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Anti-Inflamatórios não Esteroides , Dor , Adulto , Idoso , Analgésicos , Celecoxib/uso terapêutico , Diclofenaco/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Federação RussaRESUMO
The objective of the present study was to elucidate dynamics of primary allergic rhinitis (AR) morbidity in the children population of the Republic of Sakha (Yakutiya) from the statistical materials of the Yakutian Republican Information and Analytical Centre available for the period from 2008 to 2014 in the combination with the results of allergological testing based at the National Centre of Medicine, Yakutsk, that involved 100 schoolchildren presenting with allergic rhinitis who resided in the northern regions of the Republic. The results of the study give evidence of the increasing primary allergic rhinitis morbidity rate among the population of the children and adolescents during the recent years. It is concluded that the regional programs for the prevention and early diagnostics of primary allergic rhinitis need to be elaborated and introduced in the practical work of healthcare facilities over the territory of the Republic.
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Rinite Alérgica , Adolescente , Criança , Pré-Escolar , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Masculino , Prevalência , Rinite Alérgica/diagnóstico , Rinite Alérgica/epidemiologia , Rinite Alérgica/prevenção & controle , População Rural/estatística & dados numéricos , Federação Russa/epidemiologia , População Urbana/estatística & dados numéricosRESUMO
AIM: To investigate the prevalence of autoantibodies (autoAbs) associated with the development of type 1 diabetes mellitus (T1DM) in latent autoimmune diabetes of adults (LADA) in the Russian Federation. SUBJECTS AND METHODS: A total of 96 patients (46 women and 50 men) with LADA were examined. All the patients underwent an immunological examination including the determination of autoAbs, such as glutamic acid decarboxylase autoAbs (GADA), islet antigen-2 auto-Abs (IA-2A), islet cell cytoplasmic auto-Abs (ICA), zinc transporter 8 auto-Abs (ZnT8A), and insulin auto-Abs (IAA). RESULTS: GADAs were found in 61.5% of the examinees. ICAs were detected in 24%, IA-2As were observed in 57.3%. AutoAbs were more frequently observed in combination than alone. IAAs were least commonly seen in 8.3% and only in combinations. ZnT8As were found in 52.1% of the examinees and they were present alone in 5.2%. CONCLUSION: The antibodies that are most frequently observed in LADA are GADAs, IA-2As and ZnT8As. It is insufficient to identify only GADAs, as the latter are found in only 61.5% of the patients. IA-2As and ZnT8As, which are present in 57.3% and 52.1% of the patients, respectively, should also be used in the diagnosis of LADA. ICAs are much less commonly seen and along with IAAs may be additional markers for LADA.
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Proteínas de Transporte de Cátions/imunologia , Glutamato Descarboxilase/imunologia , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/imunologia , Adulto , Autoanticorpos/análise , Feminino , Humanos , Testes Imunológicos/métodos , Diabetes Autoimune Latente em Adultos/diagnóstico , Diabetes Autoimune Latente em Adultos/epidemiologia , Diabetes Autoimune Latente em Adultos/imunologia , Masculino , Federação Russa/epidemiologia , Estatística como Assunto , Transportador 8 de ZincoRESUMO
The hepatitis C virus (HCV) triggers a chronic disease that is often accompanied by a spectrum of liver pathologies and metabolic alterations. The oxidative stress that occurs in the infected cells is considered as one of the mechanisms of HCV pathogenesis. It is induced by the viral core and NS5A proteins. It is already known that both of these proteins activate the antioxidant defense system controlled by the Nrf2 transcription factor. Here, we show that this activation is mediated by domain 1 of the NS5A protein and two fragments of the core protein. In both cases, this activation is achieved through two mechanisms. One of them is mediated by reactive oxygen species (ROS) and protein kinase C, whereas the other is triggered through ROS-independent activation of casein kinase 2 and phosphoinositide 3-kinase. In the case of the HCV core, the ROS-dependent mechanism was assigned to the 37-191 a.a. fragment, while the ROS-independent mechanism was assigned to the 1-36 a.a. fragment. Such assignment of the mechanisms to different domains is the first evidence of their independence. In addition, our data revealed that intracellular localization of HCV proteins has no impact on the regulation of the antioxidant defense system.
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Novel non-competitive inhibitors of HIV RT were synthesized by alkylation of 6-substituted purines with different 2-(chloroalkyl)-2-aryl-1,3-dioxolanes and related compounds. The structure-activity relationship within the synthesized compounds was studied.
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Fármacos Anti-HIV , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/enzimologia , Purinas , Inibidores da Transcriptase Reversa , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Transcriptase Reversa do HIV/química , Humanos , Purinas/síntese química , Purinas/química , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/químicaRESUMO
This article is devoted to the probleme of modern Pediatrics pathology of the immune system in children with complicated viral infections. The aim of this study was to investigate the immune and cytokine status in children with complicated acute respiratory viral infections. The study included 100 children are often ill respiratory virus infections (more than 8 times per year) from age 0 to 7 years, and 30 children with upper respiratory tract infection; no more than 1 time per year-the control group. The standards of indicators developed by the staff of Immunological laboratory Diagnostic center of the Ministry of health of Republic Sakha (Yakutia ) together with the Institute of health of the Republic Sakha (Yakutia). Statistical calculations made on the basis of applied programs "SAS"and "SPSS"In the analysis of contingency tables (estimates of the correlation of the characteristic and evaluation of significance of differences between groups) used the criterion of 2 (Pearson and likelihood ratio and Fisher's exact test. Comparison of mean values was performed univariate analysis of variance using T-student criterion for assessing the equality of mean F-Fisher test to assess equality of variance. Extreme climatic conditions ofthe far North have an impact on immunological mechanisms. In the analysis of changes ofthe immune status revealed the greatest decline in T-cell level and components of complement in children with complications of viral respiratory infections. In children with complicated respiratory viral infections reduced cellular immunity (CD3+, CD41, CD81, CD+, CD 22+). In children with complicated respiratory viral infections decrease levels ofcytokines (IFN-y FN0-d), indicating about the risk of the formation of complications of respiratory viral infections. As a result of drug therapy of broncho-vaxom marked improvement in immune status and the absence of recurrence of respiratory viral infections within the next 3 months after therapy.
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Adjuvantes Imunológicos/uso terapêutico , Extratos Celulares/uso terapêutico , Citocinas/imunologia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/imunologia , Linfócitos T/imunologia , Viroses/imunologia , Regiões Árticas , Criança , Pré-Escolar , Temperatura Baixa , Feminino , Humanos , Sistema Imunitário , Lactente , Recém-Nascido , Masculino , Grupos Populacionais , Infecções Respiratórias/diagnóstico , Federação RussaRESUMO
Study objective. Development a system of models and procedures for the individualized internal exposure doses reconstruction for the subjects of Ukrainian State Register of persons, affected due to the Chornobyl accident (SRU) and residing in radioactive contaminated territories of Kozelets and Ripky raions of Chernihiv oblast. Materials and methods. A description the schematic diagram and mathematical equations of ecological-dosimetric models are given that allow to reconstruct the individualized exposure doses from consumption of food contaminated with radiocesium of Chornobyl origin for inhabitants of two raions of Chernihiv oblast. Parameterization of the reconstruction models is based on the mathematical analysis of results for radioecological (radiocesium milk contamination) and dosimetric (radiocesium human body burden) monitorings, that were calculated in the period of 1986-2012 in the settlements of raions under consideration. Due to quite low level of radioactive cesium depositions on the ground in 1986, the territory of these raions was divided into two "territorial zones": TZ-1, an area where the 137Cs ground depositions density in 1986 exceeds 37 kBq/m2, and TZ-2, an area where this rate does not exceeds 37 kBq/m2. For each territorial zone in each raion, the initial time moment (year) was introduced in the reconstruction model. Since this year the concept of the so-called "reference dose" has been using. Its value was assigned to all persons, regardless of the results and availability of monitoring. The results of radioecological and dosimetric monitorings were used for setting in raion specific functions: the annual average concentration of 137Cs in milk per unit of 137Cs ground depositions for Kozelets raion, function of the temporary dynamic of 137Cs concentration in milk for Ripky raion, absolute raion milk equivalent of the diet (ARMEr), and relative age dependent intake of radiocesium with the diet. Results and conclusions. Models for individualized internal exposure doses reconstruction were applied to 27811 SRU subjects from Kozelets raion and 14553 SRU subjects from Ripky raion. Results of doses individualization are given as annual average values of internal and summarized (internal and external) exposure doses for the period of 1987-2012, as well as the distribution of SRU subjects of different raions according to the intervals of accumulat-ed doses over the entire period of observation.
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Study objective. Dosimetric support of the Ukrainian State Register of persons, affected due to the Chornobyl accident (SRU). Development the system of models and procedures for the individualized internal doses reconstruction for the subjects of SRU residing in radioactive contaminated territories of Rokytne raion of Rivne oblast, Ovruch raion of Zhytomyr oblast and Ivankiv raion of Kyiv oblast. Materials and methods. A detailed description for the schematic diagram of the methodology and mathematical relations of ecological-dosimetric models are given. It allows to reconstruct the individualized doses from the ingestion of food contaminated by radiocesium after the Chornobyl accident for the subjects of SRU from three raions of Rivne, Zhytomyr and Kyiv oblasts. Phenomenologically, the developed models are close to the previously developed complex of ecological and dosimetric models intended to estimate the reference doses for the entire population of Ukraine. Calibration of model parameters is based on mathematical treatment for results of extensive radioecological (radiocesium milk contamination) and dosimetric (radiocesium burden in human body) monitorings, that were provided in the period of 1986-2012 in the settlements of raions under consideration. Completeness and periodicity of radioecological and dosimetric monitorings allowed to realize the settlement-specific approach for dose reconstruction, wherein for each settlement either the function of radiocesium intake with diet or the function of time-variation of radiocesium concentration in the local cow's milk were established. Absolute raion milk equivalent of the diet (ARMEr) and relative age dependent intake of radiocesium with diet are specified as a raion-specific functions for each raion. ARMEr is used to calculate the doses of adults in the settlement for which the function was specified. RRI is used to calculate the doses for the subjects of four children age groups (< 2 years old, 3-7 years old, 8-12 years old, 13-17 years old). Results and conclusions. Models for individualized internal exposure doses reconstruction of SRU subjects are developed. The individualized doses are estimated for 28711 SRU subjects from Rokytne raion, 18790 SRU subjects from Ivankiv raion and 41585 SRU subjects from Ovruch raion. Results of doses individualization are given as annual average doses for the period of 1987-2012. The distribution of SRU subjects of different raions over the intervals of doses accumulated over the entire observation period is also given. Values of total (from internal and external exposure) doses for SRU subjects of the raions under consideration are given, as well.
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Hepatitis C virus is one of the most spread and dangerous human pathogens. In most cases hepatitis C develops into chronic diseases which in many cases escape antiviral therapy and is associated with contributed to progression of various virus-associated organ damage and disorders including liver fibrosis, steatosis and hepatocellular carcinoma. Many of these diseases are currently linked to oxidative and ER stresses induced by the viral proteins. At the same time, hepatitis C virus disturbs systems protecting cells from these stresses, thus avoiding their effect on processes of the virus life cycle. Here, we have analyzed recent data on mechanisms of the cellular defense system functioning in infected and uninfected cells. In addition, major data on the hepatitis C virus genome structure and main functions of the virus proteins have been summarized briefly.
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Retículo Endoplasmático/metabolismo , Hepacivirus/metabolismo , Hepatite C Crônica/metabolismo , Estresse Oxidativo , Resposta a Proteínas não Dobradas , Animais , Retículo Endoplasmático/imunologia , Hepacivirus/imunologia , Hepatite C Crônica/imunologia , HumanosRESUMO
Mutations in the Leucine Reach Repeat Kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson's disease (PD). Previously, we have sequenced the coding region of the LRRK2 gene in 85 PD patients and showed the prevalence of G2019S-associated PD (G2019S-PD) among all cases of LRRK2-associated PD in Russia. Screening of the most frequent LRRK2 mutations (G2019S, R1441C, R1441G) in the extended sample of PD patients (100 familial cases, 14 relatives and 230 sporadic cases) revealed two novel families with G2019S-PD in the addition to LRRK2-associated PD cases identified earlier. In summary, the frequency of LRRK2-associated PD among familial PD cases was estimated as 8%. The G2019S mutation was the most frequent (7% - in familial and 0.5% - in sporadic PD). Comparative analyses of the age-at-onset and main neurological symptoms in 13 patients with LRRK2-associated PD (8 with G2019S, 2 - V1613A and 1 - R1441C) and 80 PD patients without mutations in the LRRK2 gene did not reveal any differences. However, the G2019S LRRK2 mutation carriers had the increased rate of drug induced side-effects in comparison with genetically undefined patients (OR=6.4, p<0.02). The data obtained could improve our understanding of the pathogenesis of LRRK2-associated PD and be useful in clinical practice during disease therapy.
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Doença de Parkinson/genética , Doença de Parkinson/fisiopatologia , Proteínas Serina-Treonina Quinases/genética , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Levodopa/uso terapêutico , Masculino , Mutação , Doença de Parkinson/tratamento farmacológico , Linhagem , Proteínas Serina-Treonina Quinases/química , Estrutura Terciária de ProteínaRESUMO
BACKGROUND AND PURPOSE: Mutations in LRRK2, encoding leucine-rich repeat kinase 2 (or Dardarin), cause autosomal dominant Parkinson's disease (AdPD) and are also found in sporadic PD (sPD). To investigate the frequency of LRRK2 mutations in a sample of Russian PD patients. METHODS: We sequenced the complete coding region of LRRK2 in 65 patients with AdPD and in 30 patients with sPD. Furthermore, in 20 patients with AdPD and in 159 patients with sPD we screened several common LRRK2 mutations (G2019S, R1441C/G/H, I2012T and I2020T). RESULTS: Five AdPD patients had the LRRK2 G2019S mutation (5.9%, 5/85). In addition, we discovered a novel LRRK2 variant V1613A in a family with a tremor dominant form of AdPD; this variant was not present in controls. We identified two patients with LRRK2 mutations in sPD: one with the G2019S mutation (0.5; 1/189) and another with the previously described R1441C mutation (0,5; 1/189). CONCLUSIONS: LRRK2 mutations are common amongst patients with PD in Russia. The results also show that the G2019S mutation is the most frequent. We identified one novel mutation in a functional region of LRRK2.
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Testes Genéticos , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Reação em Cadeia da Polimerase , Federação RussaRESUMO
The study was undertaken to define the frequency of nonclasslcal 21-hydroxylase deficiency confirmed by CYP21 gene mutations in girls with pubertal hyperandrogenlsm, to estimate the value of clinical and hormonal markers of nonclasslcal 21-hydroxylase deficiency. Eighty-five girls aged 5-17 years who had hyperandrogenlsm (pubertas precox, hirsutism, acne vulgaris). All the examinees underwent adrenocorticotropic hormone (ACTH) (Synacthen-depot) test. After detecting the hormonal markers oj"nonclassical21-hy-droxylase deficiency (the baseline level of 17- Ð HP being was above 9 nmol/l and/or above 45 nmol/l after A CTH stimulation), the authors analyzed the most common CYP21 gene mutations. The frequency of nonclassical 21-hydroxylase deficiency supported by CYP21 mutations In the girls with hyperadrogenlsm was 8.3%. There were no clinical differences between the nonclassical form of 21-hydroxylase deficiency and other forms of hyperandrogenlsm. The high baseline 17-OHP ( > 20 nmol/l) is the most specific hormonal marker of nonclasslcal 21-hydroxylase deficiency. Glucocorticoid therapy is indicated for patients with substantially accelerated growth and bone maturation and in those with menstrual irregularities as oligomenorrhea or amenorrhea.
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AIM: Screening of the population sample for articular pain and swelling. MATERIAL AND METHODS: A screening questionnaire for detection of arthritides and arthralgias was filled in for each adult rural and urban citizen aged over 18 years from 15 RF regions. Rural population was covered with a complete examination, urban one was examined by formation of a representative sample from general population. The screening covered a total of 31424 persons, mean age of whom was 47.6 +/- 17.6 years. Among them 14001 lived in the cities and 17423 in the villages. 61% respondents were women. RESULTS: Prevalence of arthralgias in the population reaches 46%. While the symptoms alleviated with time in 8%, they became chronic in the rest. The articular complaints rate in the population is sex-related and depends on the age. In persons under 20 years arthralgia occurs in 9%. Urban citizens have articular pains more frequently than rural population--43 and 33%, respectively. CONCLUSION: Pilot results of the screening program demonstrate prevalence of arthralgias in Russia and the importance of joint pathology problem in Russia.
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Artralgia/epidemiologia , Artrite/epidemiologia , População Rural , População Urbana , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Inquéritos e QuestionáriosRESUMO
Chronic experiments were performed on rats to study the main inhibitory transmitter system of the neostriatum--the GABAergic system--in the regulation of normal and pathological motor behavior. Studies addressed the effects of separate and combined administration of GABA (45 microg) and A-type receptor antagonists, i.e., picrotoxin (1 microg) and bicuculline (5 microg), into the neostriatum on the performance by rats of spontaneous (including pathological) and conditioned reflex motor behavior (active avoidance reflex in a shuttle box). Agents were injected in a volume of 1 microl daily for three weeks; control animals received physiological saline. Activation of the GABAergic system of the neostriatum had no significant effect on behavior. Conditioned reflex avoidance behavior was impaired throughout the period of bicuculline administration (there was no significant change in spontaneous behavior); this recovered after the course of microinjections finished. Picrotoxin produced smaller negative effects on performance of the reflex, though rats showed clear imperative movements in the form of choreomyoclonic hyperkinesia. Simultaneous administration of picrotoxin and GABA into the neostriatum produced less hyperkinesia; administration of picrotoxin and bicuculline altered the nature of hyperkinesia. The importance of the GABAergic system for the antihyperkinetic activity of the basal ganglia is discussed, and it is suggested that the GABA-A subsystem is of critical importance in these functions.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Bicuculina/administração & dosagem , Antagonistas GABAérgicos/administração & dosagem , Atividade Motora/efeitos dos fármacos , Neostriado/efeitos dos fármacos , Picrotoxina/administração & dosagem , Ácido gama-Aminobutírico/administração & dosagem , Animais , Aprendizagem da Esquiva/fisiologia , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Masculino , Microinjeções , Atividade Motora/fisiologia , Neostriado/fisiologia , Ratos , Ratos Wistar , Reflexo/efeitos dos fármacos , Reflexo/fisiologia , Ácido gama-Aminobutírico/fisiologiaRESUMO
The effects of daily intrastriatal bilateral microinjections of 45 mog GABA, 1 mcg of picrotoxine and 5 mcg of bicuculline on rats, were investigated. Impairment of the avoidance conditioning in shuttle box was registered in rats with picrotoxine or bicuculline and the choreo-myoklonic limb jerks, with distinct generalization stage after the picrotoxine microinjections. The combined microinjections--GABA with picrotoxine, and bicuculline with picrotoxine inhibited the hyperkinesis manifestation and changed avoidance conditioning behaviour and open-field locomotor activity. The findings suggest involvement of neostriatal GABAergic system in avoidance conditioning and complex locomotor behavioural acts regulation. The ultimate aim of the research is to find the cause, neurotransmitter mechanisms of neuromotor diseases, and to research principal new orders in treatment of neuromotor deviations.