RESUMO
The significant prevalence of periodontal diseases in elderly patients makes the research relevant. By now, the issues of complex clinical and radiological semiotics of generalized periodontitis using high-tech research methods is not sufficiently studied. The research addressed the clinical picture and three-dimensional computed tomographic semiotics of severe chronic generalized periodontitis focusing 25 elderly patients with severe chronic generalized periodontitis. It verified the necessity to use an organ-oriented program of multiplanar (volumetric) cone-beam computed tomography coupled with the analysis of the research results, as well as a mandatory analysis of densitometry indicators of the jaw bone tissue in diagnostically significant periodontal zones.
Assuntos
Tomografia Computadorizada de Feixe Cônico , Humanos , Idoso , Feminino , Masculino , Tomografia Computadorizada de Feixe Cônico/métodos , Periodontite Crônica/diagnóstico , Periodontite Crônica/epidemiologia , Periodontite Crônica/diagnóstico por imagem , Doenças Periodontais/epidemiologia , Doenças Periodontais/diagnóstico , Doenças Periodontais/diagnóstico por imagem , Pessoa de Meia-Idade , Imageamento Tridimensional/métodos , Idoso de 80 Anos ou mais , Densidade Óssea/fisiologiaRESUMO
The differentiation potential of individual clones of fibroblast CFU (CFU-F) was studied and the relative expression level of genes was analyzed in the culture of CFU-F from the bone marrow in patients with non-severe and severe forms of aplastic anemia at the onset of the disease. The differentiation potential of CFU-F clones was determined by the relative expression of marker genes using quantitative PCR. In aplastic anemia, the ratio of CFU-F clones with different differentiation potential changes, but the molecular mechanisms of this phenomenon are different in non-severe and severe aplastic anemia. In the culture of CFU-F in non-severe and severe aplastic anemia, the relative expression level of genes associated with the maintenance of the hematopoietic stem cell in the bone marrow niche changes, but the decrease in the expression of immunoregulatory genes occurs in severe form only, which may reflect differences in the pathogenesis of non-severe and severe aplastic anemia.
Assuntos
Anemia Aplástica , Humanos , Anemia Aplástica/genética , Anemia Aplástica/patologia , Medula Óssea/patologia , Células Cultivadas , Células-Tronco Hematopoéticas/patologia , Diferenciação Celular/genética , Gravidade do Paciente , Fibroblastos/patologia , Expressão Gênica/genética , Ensaio de Unidades Formadoras de ColôniasRESUMO
The tribe Triticeae includes important agricultural crops, such as bread wheat, durum wheat, barley, rye, and triticale. Research in the field of reverse genetics and genetic engineering of Triticeae received a new impetus as the CRISPR/Cas genome editing system came into broad use. The review describes and analyzes the data on recent advances in genomic editing of cultivated plants of the tribe Triticeae and tools used in the field. The tools most commonly used for genome editing in Triticeae include the codon-optimized Cas9 gene under the control of the maize ubiquitin gene promoter and guide RNAs under the control of Pol III promoters U6 and U3 in one or more binary vectors. Phosphinothricin and hygromycin resistance genes are used as selectable genes. Agrobacterium-mediated transformation and biolistics are performed to obtain genome-edited plants, and immature embryos are used as explants. Approaches developed to overcome the problem of low regenerative capacity of Triticeae include in planta transformation of shoot apical meristems, transformation of microspores and pollen grains, and the use of haploinductors. Bread wheat and barley were subject to genomic editing in the majority of studies published to date, and durum wheat and triticale were recently used in CRISPR/Cas knockout studies of target genes. Further progress in the development of genome editing of cultivated plants of the tribe Triticeae should be aimed at expanding the range of species and varieties involved and overcoming the problems of low regenerative capacity. This will allow genetic modification of elite varieties, which will be in demand in agricultural production.
Assuntos
Sistemas CRISPR-Cas , Edição de GenesRESUMO
THE AIM OF THE STUDY: The aim of the study was to develop and implement a program for the prevention of dental diseases for school-age children based on an individual approach to treatment and preventive measures. MATERIAL AND METHODS: 1848 children aged from 6 to 17 were examined. The main observation group consisted of children from school No. 1694 in the South-Western Administrative District of Moscow (935 children), the comparison group with no prevention program consisted of children from school No 1206 (913 children) of the same Moscow district. The effectiveness of the prevention program was assessed in key age groups of children 6, 12 and 15 years old. The prevention program included the study of dental morbidity, assessment of the level of oral hygiene of children, parents and teachers, conducting sanitary and educational work, teaching children hygiene and monitoring its implementation, developing and implementing the individual plan of therapeutic and preventive measures for children of all age groups. RESULTS: As a result of the prevention program, the number of healthy children without caries increased. The introduction of a prevention program showed its effectiveness, the reduction of caries growth among 12-years-old children who participated in the prevention program over 5 years was 37%, and the number of healthy children increased by 15%. CONCLUSION: Carrying out a prevention program at school has shown that coordinated actions of parents, teachers and dentists lead to an improvement in the condition of hard tissues of the permanent teeth of schoolchildren, a decrease in the risk of inflammatory periodontal diseases in adolescence, and an improvement in the quality of individual oral hygiene. Of particular importance is the presence of a dental office and a dental hygienist in the school, for the possibility of carrying out preventive measures for children of all age groups.
Assuntos
Cárie Dentária , Doenças Periodontais , Humanos , Criança , Adolescente , Serviços de Odontologia Escolar , Higiene Bucal , Cárie Dentária/epidemiologia , Cárie Dentária/prevenção & controle , Doenças Periodontais/prevenção & controle , Atenção à SaúdeRESUMO
Simulation of short bowel syndrome (SBS) in experimental animals is of great interest for studies in translational medicine. The processes of intestinal adaptation are most often studied in rats aged 8-10 weeks with up to 70% resection the small bowel. In this case, the animals are euthanized in 2 weeks after the surgery; further development of the pathological process remains practically unexplored. In our experiment, a number of blood biochemical parameters and morphological signs of intestinal adaptation were assessed within 34 weeks after surgery. It was shown that after resection of 70% of the small bowel in rats (180±15 g), clinical symptoms are observed only during the first 2 weeks, however, the mortality in the group was observed throughout the entire period of the study in the absence of clear clinical signs. Morphological compensatory changes in the walls of the small intestine continued up to 34 weeks after resection, and their morphometry can be used to describe adaptation in the dynamics of the study.
Assuntos
Síndrome do Intestino Curto , Adaptação Fisiológica , Animais , Modelos Animais de Doenças , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Intestinos/patologia , Ratos , Roedores , Síndrome do Intestino Curto/patologia , Síndrome do Intestino Curto/cirurgiaRESUMO
The properties of bone marrow-derived multipotent mesenchymal stromal cells (MSC) of patients with aplastic anemia at the onset of the disease are studied insufficiently. The aim of this work was to test the ability of MSC from patients with aplastic anemia to maintain hematopoietic precursors and to analyze the expression of genes associated with hematopoiesis and immune response. The ability of MSC to maintain hematopoietic precursors was determined by counting cobblestone area-forming cells; gene expression was analyzed by quantitative PCR. It was shown that MSC of patients with aplastic anemia preserve their ability to maintain hematopoietic precursors. Pronounced changes in the expression of the VEGFA and ANGPT1 genes were found. MSC from aplastic anemia patients with PNH clone significantly differ from those from aplastic anemia patients without PNH clone in terms of the expression of the SDF1, IL1R, and VEGFA genes. Changes in gene expression can be associated with the pathogenesis of the disease.
Assuntos
Anemia Aplástica , Células-Tronco Mesenquimais , Anemia Aplástica/genética , Anemia Aplástica/patologia , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Expressão Gênica , Hematopoese , Humanos , Células-Tronco Mesenquimais/metabolismoRESUMO
Childhood obesity is an urgent problem of pediatric endocrinology due to the widespread occurrence, the development of metabolic complications and their steady tracking into adulthood. The developed clinical guidelines are the main working tool of the practitioner. They briefly and structurally present the main information about the epidemiology and modern classification of obesity, methods of its diagnosis and treatment based on the principles of evidence-based medicine.
Assuntos
Endocrinologia , Obesidade Infantil , Adulto , Criança , Medicina Baseada em Evidências , Humanos , Obesidade Infantil/diagnóstico , Obesidade Infantil/epidemiologia , Obesidade Infantil/terapiaRESUMO
The aim of the study was to evaluate the levels of mediators of the immune response, cellular immunity, and phagocytic activity in patients with chickenpox with various values of the clinical and laboratory parameters and propose criteria for predicting the severity and complications of the disease. MATERIALS AND METHODS: The blood levels of pro-inflammatory mediators were evaluated by ELISA using monoclonal antibodies (Protein Contour, Russia). RESULTS: The inflammatory mediators and neutrophil chemiluminescence were studied in patients with either presence or absence of Varicella zoster DNA. We found that in patients with positive viral DNA, the levels of IFN-α and IFN-γ were significantly lower compared to patients with negative DNA results. Thus, complications of chickenpox, in particular secondary viral-bacterial pneumonia, can be predicted based on low (less than double-normal) levels of IL-6 and IFN-γ, induced chemiluminescence, CD16, and CD20. This type of immune response indicates the state of immune deficiency with prevailing suppression of the T-effector and phagocytic mechanisms in these patients. CONCLUSION: Prognosis of the development of severe and complicated forms of chickenpox can be based on the insufficiently increased (less than two normal values) levels of IL-6 and IFN-γ, induced chemiluminescence, CD16, and CD20. These relatively low levels are indicative of reduced immune response to the infection, which may require additional immune correcting therapy.
Assuntos
Varicela , Herpes Zoster , Herpesvirus Humano 3 , Humanos , Imunidade Celular , Interferon gamaRESUMO
A group of 27 healthy young adults solved a task involving the working memory (WM) activation, consisting of the comparison between the spatial orientations of two sequentially presented square-wave luminance gratings. We investigated the effective (directed) connectivity patterns between the frontal and postcentral cortical regions related to the visual system. The connectivity was assessed using vector autoregression modeling of EEG. It was shown that the strength of the top-down right-hemispheric connectivity patterns directed from the frontal cortex to the visual areas in θ frequency was significantly lower at the stage of stimulus retention in the WM than at the stage of stimulus anticipation. On the contrary, in the α band the descending influences were slightly more intense. The results of the study showed the frequency-dependent dynamics of the descending influences of the frontal cortex on visual areas and confirm that the frontal cortex plays the role of a controlling and modulating center in the brain system underlying WM.
Assuntos
Lobo Frontal , Memória de Curto Prazo , Encéfalo , Eletroencefalografia , Memória EspacialRESUMO
Telomere length can be measured by polymerase chain reaction (PCR), allowing to obtain the absolute length of telomeres (ALT) in base pair, and by flow cytometry, which can only estimate the relative telomere length. The aim of the study was to compare the results of the two methods and to develop an accurate and reliable way of converting the relative telomere length to absolute. The peripheral blood from 21 donors was analyzed. Measurement of leukocyte telomere length by flow cytometry was carried out using a commercial Telomere PNA Kit / FITC (Dako, Denmark) with two CytoFLEX flow cytometers (Beckman Coulter, China) and BD FACSCanto II (Becton Dickinson, USA), obtaining the molecular equivalent of fluorescence (MEF). To measure telomere length by real-time PCR, calibrators with a known number of telomeric repeats were prepared. Two quantitative PCRs were carried out: one for telomeric repeats, the other for determining the number of genome-equivalents of DNA, three times for each sample, which made it possible to calculate ALT. A strong direct relationship was found between the MEF obtained with BD FACSCanto II and CytoFLEX (r = 0.97). Analysis of PCR and flow cytometry results showed a significant correlation between ALT and MEF. We calculated the regression equations of ALT and MEF for CytoFLEX - y = 0.0043x (r = 0.84) and for BD FACSCanto II - y = 0.0051x (r = 0.82). Correlation analysis showed a high comparability of telomere lengths measured by two methods. The obtained regression equations allow converting the results of flow cytometry into absolute values, allowing the comparison of the results of different research groups and the use of this method in clinical trials.
Assuntos
Leucócitos , Telômero , DNA , Citometria de Fluxo , Humanos , Hibridização in Situ Fluorescente , Telômero/genéticaRESUMO
Immunomodulatory drugs are widely used as drugs for the treatment of inflammatory diseases of microbial etiology in clinical medicine. The authors evaluated the effectiveness of the therapeutic effect of the Cycloferon immunomodulator in the treatment of chronic purulent-inflammatory diseases of the reproductive tract using clinical, microbiological and immunological parameters. It was shown that under the influence of immunomodulatory therapy, the restoration of the qualitative and quantitative composition of the normoflora was observed with the elimination of etiologically significant microorganisms. The immunocorrective effect of therapy on the indices of local immunity was established: the concentration of lactoferrin increased in the cervical secretion, the level of cytokines IL-1ß and γ-IFN normalized, the amount of secretory IgA increased significantly, which contributed to the enhancement of local protective reactions, as well as the clinical efficacy of therapy, which was manifested in the reduction and/or disappearance of pain syndrome and the absence of relapse for 2 or more years. Conducted researches allow us to speak of immunotropic drugs as a promising direction in the treatment of inflammatory processes of the reproductive tract, a significant advantage of which is rational immunomodulation directly in the focus of inflammation, the availability of treatment, the absence of side effects with adequate therapeutic regimens, which makes it relevant to further study this direction of immunocorrection and its implementation into wide clinical practice.
Assuntos
Citocinas , Imunomodulação , Humanos , Imunidade , InflamaçãoRESUMO
Dyskeratosis congenita (DC) is a hereditary syndrome of bone marrow failure, which develops because of telomeres defects and combines with cancer predisposition. Its classical clinical features are skin pigmentation, nail dystrophy, oral leukoplakia (skin-mucosa triad). The goal is to describe the algorithm of diagnosis, clinical specificities of DC and specific treatment for cases of DC in one family. The present report includes descriptions of diagnosis and treatment of family members diagnosed for the first time as having a DC. The report shows an importance of all diagnostic stages: from a medical history and clinical picture to an application of modern high-tech diagnostic methods (flow-FISH, NGS). The report underlines an importance of diagnosis of all family members for excluding an asymptomatic form after a case of DC has been already detected in that family. A high frequency of a toxicity and secondary neoplasia makes it necessary to realize an individual approach at treatment of each patient with DC (the earliest start of androgen treatment, prompt decision of implementation of allogenic hematopoietic stem cell transplantation). The knowledge of pathogenesis, clinical features and principles of diagnosis and therapy of this disease is relevant to pediatricians and hematologists.
Assuntos
Disceratose Congênita , Transplante de Células-Tronco Hematopoéticas , Humanos , Androgênios , Disceratose Congênita/diagnóstico , Disceratose Congênita/genética , Disceratose Congênita/terapiaRESUMO
Given the ability of molecular chaperones and chaperone-like proteins to inhibit the formation of pathological amyloid fibrils, the chaperone-based therapy of amyloidosis has recently been proposed. However, since these diseases are often diagnosed at the stages when a large amount of amyloids is already accumulated in the patient's body, in this work we pay attention to the undeservedly poorly studied problem of chaperone and chaperone-like proteins' effect on mature amyloid fibrils. We showed that a heat shock protein alpha-B-crystallin, which is capable of inhibiting fibrillogenesis and is found in large quantities as a part of amyloid plaques, can induce degradation of mature amyloids by two different mechanisms. Under physiological conditions, alpha-B-crystallin induces fluffing and unweaving of amyloid fibrils, which leads to a partial decrease in their structural ordering without lowering their stability and can increase their cytotoxicity. We found a higher correlation between the rate and effectiveness of amyloids degradation with the size of fibrils clusters rather than with amino acid sequence of amyloidogenic protein. Some external effects (such as an increase in medium acidity) can lead to a change in the mechanism of fibrils degradation induced by alpha-B-crystallin: amyloid fibers are fragmented without changing their secondary structure and properties. According to recent data, fibrils cutting can lead to the generation of seeds for new bona fide amyloid fibrils and accelerate the accumulation of amyloids, as well as enhance the ability of fibrils to disrupt membranes and to reduce cell viability. Our results emphasize the need to test the chaperone effect not only on fibrillogenesis, but also on the mature amyloid fibrils, including stress conditions, in order to avoid undesirable disease progression during chaperone-based therapy.
Assuntos
Amiloide/química , Cadeia B de alfa-Cristalina/química , Amiloide/efeitos dos fármacos , Células HeLa , Humanos , Muramidase/química , Conformação Proteica , Cadeia B de alfa-Cristalina/farmacologia , Microglobulina beta-2/químicaRESUMO
OBJECTIVE: To study oxidative stress in young patients with focal symptomatic and cryptogenic epilepsy and after the new-onset epileptic seizures. MATERIAL AND METHODS: Patients, aged from 19 to 44 years, were distributed into three groups, 30 patients in each: patients after a few (first) epileptic seizures, patients in the clinical remission that has lasted at least one year, and patients with treatment-resistant epileptic seizures. The control group included 20 healthy people. Parameters of the pro-oxidant status (TBA-reactive products) and the antioxidant defense (total superoxide-scavenging activity, catalase, total antioxidant activity, and reduced thiols (SH groups)) were measured in the blood plasma. RESULTS: No significant differences in the concentrations of TBA-reactive products were identified in patients with epilepsy compared with healthy controls while concentrations of reduced SH groups, total superoxide-scavenging activity, catalase activity and the total antioxidant activity were significantly decreased in patients. In addition, some of the parameters displayed significant differences between different groups of patients. CONCLUSION: In patients with epilepsy, the changes in the free-radical processes are seen already after the first seizures and persist in the treatment-resistant epilepsy and in clinical remission. Since the parameters of the activity of the antioxidant defense are significantly different in different groups of patients, one can assume that different elements of the oxidative stress are present after the first epileptic seizures and in different courses of the disease.
Assuntos
Epilepsia , Adulto , Antioxidantes , Catalase , Humanos , Estresse Oxidativo , Convulsões , Adulto JovemRESUMO
In this work, we have compared malignant and non-malignant diseases of the mammary gland using 8 proteins: HRG, MUC1, PAI-1, HSP90αA1, CDH1, ERα, PGR and IL-12. Their concentrations in the supernatants of blood cells and breast biopsies were compared in terms of spontaneous production, induced by a polyclonal activator and after exposure to biopsy samples of the HLDF differentiation factor, as well as the indices of the effect of the polyclonal activator and HLDF on the protein production. In addition, the correlation relationships of the above indicators with the expression of markers of the epithelial-mesenchymal transition: collagen type II (CII), ß-1 integrin (CD29) and cadherin-E (CDH1) were studied. The study revealed statistically significant differences in the concentration of HRG in the supernatant of blood cells, IL-12 during spontaneous production by biopsy specimens, PGR production of biopsy specimens induced by the polyclonal activator, CDH1 and IL-12 production biopsy specimens exposed to HLDF. According to the influence index of the polyclonal activator and HLDF, statistically significant differences were found for CDH1production. Comparison of non-specific invasive carcinoma biopsy specimens and non-malignant breast diseases by means of the markers of the epithelial-mesenchymal transition revealed statistically significant differences in CD29 expression and the lack of differences in the expression of CDH1 and CII. This indicates the presence of cell atypia in samples of non-malignant breast diseases; it is confirmed by the recognized correlation between the production of certain proteins and the expression of the epithelial-mesenchymal transition markers.
Assuntos
Biomarcadores , Doenças Mamárias/diagnóstico , Neoplasias da Mama/diagnóstico , Proteínas/análise , Transição Epitelial-Mesenquimal , Feminino , HumanosRESUMO
CRISPR/Cas technology of genome editing is a powerful tool for making targeted changes in the DNA of various organisms, including plants. The choice of the precise nucleotide sequence (protospacer) in the gene to be edited is important in the design of guide RNA, which can be carried out by specialized software. We review and compare all the known on-line and off-line resources for guide RNA design, with special attention paid to tools capable of searching for off-target edits sites in plant genomes. The use of Cas12a may be preferable to Cas9. Techniques allowing CâT and GâA base editing without DNA cleavage are discussed along with the basic requirements for the design of effective and highly specific guide RNAs. Ways for improving guide RNA design software are presented. We also discuss the lesser risks of off-target editing in plant genomes as opposed to animal genomes. Examples of edited plant genomes including those that do not lead to the creation of transgenic plants are reviewed.
Assuntos
Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Genoma de Planta/genética , RNA Guia de Cinetoplastídeos/genéticaRESUMO
Breast cancer, in most cases, is a malignant neoplasm associated with infiltration of a tumor with the cells that form its microenvironment and produce various cytokines. The aim of the study was to evaluate the cytokine-producing function of tumor cells and their microenvironment in biopsy specimen of patients with invasive carcinoma of no special type and in patients with benign breast diseases. To assess the cytokine-producing activity of the tumor and its microenvironment, the index of polyclonal activators influence on cytokine production by biopsy specimens of patients with invasive carcinoma of no special type (group I) and in patients with benign breast tumors (group II) was calculated. Group II was further subdivided into group IIa, which included only patients with fibroadenoma, and group IIb, which included the patients with leaf-shaped fibroadenoma, fibroadenomatosis, fibrocystic mastopathy, intraductal papillomatosis, sclerosing adenosis and fibrocystic mastopathy with microcalcifications. The concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ß, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 were measured in tumor biopsy supernatants. When comparing groups I and II, higher indices of the polyclonal activators influence on the production of IL-17, IL-18 and TNF-α were observed in patients with benign diseases. Higher indices of the polyclonal activators influence on the production of IL-18, TNF-α, and IL-1ß and the ratio of IL1ß/IL1Ra were observed in patients with fibroadenoma as compared to those with invasive carcinoma of no special type. There were no significant differences in the indices of the polyclonal activators influence between groups I and IIb. This suggests the existence of changes in the mammary gland in patients of group IIb similar to those present in patients with invasive carcinoma of no special type. Higher indices of polyclonal activators influence on the production of IL-1ß, as well as the ratio of IL1ß/IL1Ra were observed in the patients of group IIa compared to the patients of group IIb. The results of the study identify the features of the cytokine-producing resource of tumor biopsy specimens in patients with invasive carcinoma of no special type and with benign breast tumors.
Assuntos
Doenças Mamárias/imunologia , Neoplasias da Mama/imunologia , Carcinoma/imunologia , Citocinas/imunologia , Microambiente Tumoral , Biópsia , HumanosRESUMO
AIM: To study the influence of the state of endothelium on the daily profile of arterial pressure (AP) in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: In 70 RA pts carried out C-reactive protein (CRP), vascular endothelial adhesion molecule type 1 (sVCAM-1), antigen von Willebrand Factor (AG WF), interleukin-8 (Il-8), rheumatoid factor (RF), IgG, endotheline-1 (ET-1), number of desquamated endotheliocytes cells (DE), VS, activity of renin by immunoenzyme analysis. The dysfunction of endothelium was evaluated by calculation of DE. The functional methods included the daily monitoring of arterial pressure (AP). RESULTS: Arterial hypertension (AH) occurred in 40 (57.1%) pts. RA pts are revealed the signs of endothelial dysfunction, about which significant differences among the indices of activation of endothelium in comparison with control group testify. ET-1, sVCAM-1, vWF AG, Il-8, CRP content was higher in RA pts. Reliably above there was a number of DE. Reliable differences according to these indices depending of RA activity were discovered. With conducting of correlation analysis it is revealed, that markers of the activation of endothelium: sVCAM-1, vWF AG positively correlated with increasing RF IgG and indices of the immune inflammation: CRP, and DE number. In patients suffering from RA, showed signs of endothelial dysfunction. The positive correlation between endothelial damage and daily profile of AP show the relationship of these processes. CONCLUSION: Positive correlations between the damage of endothelium and disturbance of AP daily profile testify about the interrelation of these processes.
Assuntos
Artrite Reumatoide , Endotélio Vascular , Artrite Reumatoide/complicações , Biomarcadores , Pressão Sanguínea , Endotélio Vascular/patologia , Humanos , Fator Reumatoide , Molécula 1 de Adesão de Célula Vascular , Fator de von WillebrandRESUMO
The amplitudes of the P100 and N150 early components of evoked potentials in the visual cortex have been analyzed on 33 volunteers with normal vision during matching between the current orientation and that stored in memory. An increase in the P100 response in the occipital and parietal cortical areas was identified as an informative indicator of mismatch between the current and stored-in-memory orientations. This effect was not found for more complex stimuli, namely, spatial patterns. The N150 component demonstrated a similar effect, but in contrast to P100 it was not stimulus specific. Thus, in the first 100 ms, a signal of mismatch between the current and stored-in-memory orientations arises in the early visual areas that represents a mechanism for early implicit response to changes in the basic characteristics of the visual space.
Assuntos
Memória de Curto Prazo , Memória Espacial , Córtex Visual/fisiologia , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Recently, we identified the yeast red pigment (RP), a polymer of 1-(5'-Phosphoribosyl)-5-aminoimidazole, as a novel potential anti-amyloid agent for the therapy of neurodegenerative diseases. The purpose of this study was to further validate RP for treatment of Parkinson's disease (PD) and to clarify molecular mechanisms involved in the reduction of amyloid cytotoxicity. We investigated RP effects in vivo using Saccharomyces cerevisiae and Drosophila melanogaster PD models. Western blot analysis revealed reduction in the levels of insoluble α-synuclein in both models, while soluble α-synuclein decreased only in Drosophila. In both models RP significantly reduced α-synuclein cytotoxicity, as was revealed by immunohistochemistry in Drosophila (pâ¯<â¯0.001, nâ¯=â¯27 flies per genotype/assay) and by flow cytometry in yeast (pâ¯<â¯0.05). Data obtained from the yeast PD model suggests that RP antitoxic effects are associated with a drop in ROS accumulation, and slower cellular transition from the early to late apoptotic stage. Using Drosophila brain tissue sections, we have demonstrated that RP helps to compensate for an α-synuclein-mediated reduction in the number of dopaminergic neurons and leads to better performance in animal climbing tests (pâ¯<â¯0.001, nâ¯=â¯120-150 flies per genotype/assay). Taken together, these results demonstrate the potential of RP for the treatment of PD, at least in model systems.