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Neuroscience Bulletin ; (6): 290-302, 2022.
Article in English | WPRIM | ID: wpr-929083


Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.

Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Animals , Cognition , Disease Models, Animal , Mice , Mice, Transgenic , Monocytes/pathology , Polysaccharides/therapeutic use , Proteoglycans
Chinese Medical Journal ; (24): 591-597, 2022.
Article in English | WPRIM | ID: wpr-927512


BACKGROUND@#Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.@*METHODS@#We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.@*RESULTS@#The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.@*CONCLUSION@#Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.

Aged , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Arteries , Atrophy , Brain/metabolism , Cerebral Cortex/metabolism , Cerebrovascular Circulation , Constriction, Pathologic/pathology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Positron-Emission Tomography/methods
Int. j. morphol ; 38(1): 230-234, Feb. 2020. graf
Article in English | LILACS | ID: biblio-1056427


The hypotheses currently considered the most likely causes of Alzheimer's disease (AD) are amyloid beta peptide deposition in the cerebral cortex and hyperphosphorylation of the Tau protein, with the consequent formation of neurofibrillary tangles. In clinical practice, although not accurate, AD diagnosis is based on the exclusion of other diseases, behavioural assessments and complementary examinations, such as imaging and blood tests. Advances in the field of biotechnology have created exciting prospects for the early detection of AD via biomarker assessment, which is considered a safer and more efficient procedure. Molecules recognised as biomarkers can be expressed in some body fluids, including cerebrospinal fluid, saliva and blood. The presence of amyloid beta peptide and Tau can be confirmed in saliva, which is also an easily and non-invasively collectable material with an accessible cost. The objective was evaluate the concentrations of the t-Tau protein and Ab42 peptide in the saliva of elderly individuals with and without dementia of the AD type Method: The objective of this case-control study, involving a total of 120 individuals, was to analyse whether a correlation exists between variations in the concentrations of the t-Tau and Ab42 biomarkers in the saliva of patients with confirmed AD and individuals in the inclusion group but without AD . We found that t-Tau expression in AD patients is significantly lower than that in individuals without AD, whereas the salivary concentration of Ab42 is higher in patients with AD but not significantly different from that of the group without AD. Conclusion: Thus, we demonstrate the feasibility of using salivary biomarkers as predictive markers for diagnosis of Alzheimer's disease.

Las hipótesis consideradas actualmente como las causas más probables de la enfermedad de Alzheimer (EA) son la deposición de péptido beta amiloide en la corteza cerebral y la hiperfosforilación de la proteína Tau, con la consiguiente formación de ovillos neurofibrilares. En la práctica clínica, aunque no es precisa, el diagnóstico de la EA se basa en la exclusión de otras enfermedades, evaluaciones de comportamiento y exámenes complementarios, como imágenes y análisis de sangre. Los avances en el campo de la biotecnología han creado interesantes perspectivas para la detección temprana de la EA a través de la evaluación de biomarcadores, que se considera un procedimiento más seguro y más eficiente. Las moléculas reconocidas como biomarcadores se pueden expresar en algunos fluidos corporales, incluidos el líquido cerebroespinal, la saliva y la sangre. La presencia del péptido beta amiloide (AB) y la proteína Tau (t-Tau) se puede confirmar en la saliva, que también es un material fácil y no invasivo de recolección con un costo accesible. El objetivo fue evaluar las concentraciones de la proteína t-Tau y el péptido Ab42 en la saliva de las personas de edad avanzada con y sin demencia del tipo de tipo EA. El estudio de casos y controles, se realizó en un total de 120 personas, para analizar si existe una correlación entre las variaciones en las concentraciones de los biomarcadores t-Tau y Ab42 en la saliva de pacientes con EA confirmada e individuos en el grupo de inclusión pero sin AD. Encontramos que la expresión de t-Tau en pacientes con EA es significativamente menor que en individuos sin EA, mientras que la concentración salival de Ab42 es mayor en pacientes con EA pero no significativamente diferente de la del grupo sin la enfermedad . Por lo tanto, se demuestra la viabilidad del uso de biomarcadores salivales como marcadores predictivos para el diagnóstico de la enfermedad de Alzheimer.

Humans , Male , Female , Middle Aged , Aged , Amyloid beta-Peptides/metabolism , tau Proteins/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Saliva/metabolism , Saliva/chemistry , Biomarkers/analysis , Biomarkers/metabolism , Amyloid beta-Peptides/analysis , tau Proteins/analysis
Braz. J. Pharm. Sci. (Online) ; 56: e17797, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132045


Oral fast-dispersible film was prepared by utlizing donepezil hydrochloride (drug) and various cellulose derivatives such as hydroxypropyl methyl cellulose (hypermellose) (HPMC), microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC) to treat Alzheimer's disease. NCC was synthesized by ultra-sonication method using MCC and this was converted to thinfilm formulation (NCC-F) using solvent casting technique. The interaction between the polymer and the drug was investigated by spectral analysis such as UV, FTIR, and 1H- NMR. FTIR confirmed that the compatibility of drug and polymer in ODF formulation. NCC-F has shown an average surface roughness of 77.04 nm from AFM and the average particle size of 300 nm from SEM analysis. Nano sized particle of NCC-F leads faster in vitro dissolution rate (94.53%) when compared with MCC-F and F3 formulation. Animal model (in vivo) studies of NCC-F formulation has reached peak plasma concentration (Cmax) up to 19.018 ng/mL in the span of (tmax) 4 h with greater relative bioavailability of 143.1%. These results suggested that high surface roughness with nanosized NCC-F formulation attained extended drug availability up to (t1/2) 70 h.

Animals , Male , Female , Rats , In Vitro Techniques/methods , Dissolution/classification , Donepezil/agonists , Sonication/methods , Pharmaceutical Preparations/analysis , Cellulose , Spectroscopy, Fourier Transform Infrared/methods , Models, Animal , Alzheimer Disease/pathology
Rev Assoc Med Bras (1992) ; 66(4): 512-515, 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1136220


RESUMO Pesquisas recentes demonstram que o hipocampo apresenta uma redução de volume no final da idade adulta, mantendo uma estreita relação com o declínio cognitivo. A aquisição da imagem por diversos métodos de medição de volume nos leva a encontrar na ressonância magnética o método de destaque, pois permite quantificar o volume de determinadas estruturas cerebrais utilizando a reconstrução computadorizada tridimensional das imagens obtidas. OBJETIVOS Confirmar a existência de diferenças entre o volume hipocampal e o declínio cognitivo leve, doença de Alzheimer e cognição normal. MÉTODOS Levantamento bibliográfico de estudos que apresentassem dados referentes aos distúrbios da doença de Alzheimer, alterações macroscópicas cerebrais detectadas com softwares na ressonância magnética e segmentação. Foram adicionados estudos apenas da medição volumétrica do hipocampo, objetivando-se chegar a valores que possam estabelecer uma correlação do menor valor estrutural hipocampal e risco de desenvolvimento da doença. RESULTADOS Um total de 1.070 indivíduos foi analisado em seis estudos clínicos, demonstrando a relação da diminuição do hipocampo na neuroimagem, correlacionado com o comprometimento cognitivo leve e doença de Alzheimer. CONCLUSÕES O desenvolvimento de um valor padrão para esse fim seria bastante útil na coleta de dados, permitindo melhor compreensão de algumas alterações que podem ocorrer na cognição, determinar valores prognósticos e até, em um futuro próximo, fator de risco imagiológico para a doença.

Humans , Magnetic Resonance Spectroscopy/methods , Alzheimer Disease/pathology , Cognitive Dysfunction , Hippocampus/diagnostic imaging , Titrimetry , Hippocampus/anatomy & histology , Hippocampus/pathology
Acta fisiátrica ; 24(2): 82-85, jun. 2017. graf, tab
Article in English, Portuguese | LILACS | ID: biblio-906914


Objetivo: Avaliar a funcionalidade de pacientes com Doença de Alzheimer (DA) residentes na comunidade, no município de Guarapuava ­ PR, região Sul do Brasil. Métodos: Foi realizado um estudo transversal, com pacientes com DA residentes na comunidade, no município de Guarapuava ­ PR. Os participantes foram classificados de acordo com a Escala Clínica de Demência em CDR 1 (DA leve), CDR 2 (DA moderada) e CDR 3 (DA severa). O estado mental foi avaliado através do Mini Exame do Estado Mental; as atividades básicas de vida diária (ABVD) através do Índice de Barthel e as atividades instrumentais de vida diária (AIVD) através do Índice de Lowton e Brody. Resultados: Foram avaliados 58 idosos com diagnóstico de DA, dos quais 14 (24,1%) estavam em CDR 1, 21 (36,2%) em CDR 2 e 23 (39,7%) em CDR 3. Houve diferença significativa entre os níveis de dependência para a realização das ABVD e AIVD entre todas as fases da DA (p <0,001), sendo que a dependência foi maior nos participantes estadeados em CDR 2 e CDR 3. Conclusão: O nível de dependência para a realização das atividades básicas e instrumentais de vida diária é maior nas fases mais avançadas da DA e a dependência para a realização das AIVD está presente em todas as fases da doença, sendo maior do que a dependência para a realização das ABVD desde a fase inicial da DA, sugerindo uma perda progressiva da funcionalidade

Objective: To evaluate the functionality of patients with Alzheimer's disease (AD) living in a community, in the city of Guarapuava PR, South of Brazil. Methods: A cross-sectional study was performed with patients with AD living in the community. Participants were classified according to Clinical Dementia Rating as CDR 1 (mild AD), CDR 2 (moderate AD) and CDR 3 (severe AD). The mental state was assessed by the Mini Mental State Examination; the basic activities of daily living (ADLs) was determined by the Barthel Index and instrumental activities of daily living (IADLs) via by Lowton and Brody Index. Results: 49 elderly patients with AD diagnosis were evaluated, 14 (24.1%) of which were classified as CDR 1, 21 (36.2%) as CDR 2, and 23 (39.7%) as CDR 3. There was a significant difference between the levels of dependence for the performance of the basic ADLs and IADLs among all phases of AD (p <0.001). The dependence was higher in both CDR 2 and CDR 3. Conclusion: Functional dependence for basic activities of daily living becomes more frequent in the most advanced stages of AD, whereas dependence for IADLs is onset since early stages of AD, even more noticeable than dependence for basic ADLs, what suggests a progressive loss of functionality

Humans , Activities of Daily Living , Alzheimer Disease/pathology , Cross-Sectional Studies , Cognitive Dysfunction
Arq. neuropsiquiatr ; 74(9): 737-744, Sept. 2016. graf
Article in English | LILACS | ID: lil-796045


ABSTRACT Cell physiology is impaired before protein aggregation and this may be more relevant than inclusions themselves for neurodegeneration. The present study aimed to characterize an animal model to enable the analysis of the cell biology before and after protein aggregation. Ten-month-old Lewis rats were exposed either to 1 or 2 mg/kg/day of rotenone, delivered subcutaneously through mini-pumps, for one month. Hyperphosphorylated TAU, alpha-synuclein, amyloid-beta peptide and protein carbonylation (indicative of oxidative stress) were evaluated in the hippocampus, substantia nigra and locus coeruleus through immunohistochemistry or western blot. It was found that 2 mg/kg/day rotenone increased amyloid-beta peptide, hyperphosphorylation of TAU and alpha-synuclein. Rotenone at 1mg/kg/day did not alter protein levels. Protein carbonylation remained unchanged. This study demonstrated that aged Lewis rats exposed to a low dose of rotenone is a useful model to study cellular processes before protein aggregation, while the higher dose makes a good model to study the effects of protein inclusions.

RESUMO A fisiologia celular está prejudicada antes da agregação proteica podendo ser mais importante para a neurodegeneração do que as próprias inclusões. Assim, o objetivo deste estudo é caracterizar um modelo animal para analisar os mecanismos e efeitos da agregação proteica. Ratos Lewis com 10 meses de idade foram expostos a rotenona (1 ou 2 mg/kg/dia), administrada subcutaneamente, utilizando minibombas osmóticas. Os níveis de peptídeo beta-amiloide, TAU hiperfosforilada, alfa-sinucleína e proteínas carboniladas (indicativo de estresse oxidativo) foram avaliados por imunohistoquímica e western blot no hipocampo, substância negra e locus coeruleus. Foi demonstrado que 2 mg/kg/dia de rotenona promoveu aumento do peptídeo beta-amiloide, hiperfosforilação da TAU e alfa-sinucleína. Já 1 mg/kg/dia de rotenona não alterou os níveis dessas proteína nessas regiões. As proteínas carboniladas não se alteraram. Foi demonstrado que ratos Lewis idosos expostos a baixas doses de rotenona são modelo de estudo dos processos celulares antes da agregação proteica, enquanto 2 mg/kg/dia de rotenona permite estudos sobre os efeitos da agregação proteica.

Animals , Male , Rotenone/administration & dosage , Central Nervous System/drug effects , Central Nervous System/pathology , Disease Models, Animal , Protein Aggregation, Pathological/chemically induced , Protein Aggregation, Pathological/pathology , Rats, Inbred Lew , Substantia Nigra/drug effects , Immunohistochemistry , Central Nervous System/metabolism , Blotting, Western , Reproducibility of Results , Amyloid beta-Peptides/drug effects , Amyloid beta-Peptides/metabolism , Oxidative Stress , alpha-Synuclein/drug effects , alpha-Synuclein/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology
Rev. cuba. enferm ; 31(4): 0-0, oct.-dic. 2015. ilus, tab
Article in Portuguese | LILACS, BDENF, CUMED | ID: lil-797705


Introdução: a doença de Alzheimer é a demência mais prevalente na prática clínica da enfermagem. Esta patologia caracteriza-se pela presença de placas amielóides e emaranhados neurofibrilares no cérebro, bem como diminuição geral do cérebro e do número de neurônios. Objetivo: elencar a produção da literatura nacional dos enfermeiros brasileiros sobre o cuidado aos idosos com doença de Alzheimer no período de 2000 a 2011. Métodos: revisão integrativa da literatura, seguindo os pressupostos de Cooper. Foram utilizados os descritores: idoso sendo refinado com o descritor doença de Alzheimer. A busca teve o espaço temporal especificado entre os anos 2000 a 2011. Foram incluídas publicações científicas brasileiras, indexadas na base de dados Literatura Latino Americana do Caribe em Ciências da Saúde, Banco de Dados de Enfermagem e, na Literatura Internacional em Ciências da Saúde que apresentassem o resumo disponível on-line; no idioma português. Conclusão: percebe-se que a maioria das publicações referem-se aos cuidadores e a saúde destes, o que sugere a necessidade de novas pesquisas que visem a construção de plano de cuidados aos idosos com Alzheimer(AU)

Introducción: la enfermedad de Alzheimer es la demencia más frecuente en la práctica clínica de enfermería. Esta patología se caracteriza por la presencia de amielóides placas y ovillos neurofibrilares en el cerebro, y el cerebro y disminución general en el número de neuronas. Objetivo: distinguir la producción de literatura nacional de enfermería sobre el cuidado a ancianos con enfermedad de Alzheimer en el período de 2000 a 2011. Métodos: revisión integrativa de literatura, ciñéndose a los presupuestos de Cooper. Fue utilizado el descriptor Anciano, refinándose la búsqueda con el descriptor enfermedad de Alzheimer. La búsqueda se efectuó de acuerdo al periodo precitado. Fueron incluidas publicaciones científicas brasileñas, indexadas en la base de datos Literatura Latinoamericana y del Caribe en Ciencias de Salud, Banco de Datos de Enfermería y Literatura Internacional en Ciencias de Salud, que presentaran resumen disponible online en lengua portuguesa. Conclusión: se percibe que la mayoría de las publicaciones se refieren a los cuidadores y a su salud, lo cual sugiere la necesidad de nuevas investigaciones apuntando a construir un plan de cuidado a los ancianos con Alzheimer(AU)

Introduction: Alzheimer's disease is the most prevalent dementia in clinical nursing practice. This pathology is characterized by the presence of amielóides plaques and neurofibrillary tangles in the brain, and the brain and general decrease in the number of neurons. Objective: to list the national literature output by Brazilian nurses regarding the care to elderly patients with Alzheimer disease, in the period spanning from 2000 to 2011. Method: integrative literature review, according to Cooper's premises. The following descriptors were used: elderly, refine with the descriptor Alzheimer disease. The search was limited to the period between the years 2000 and 2011. The included articles were Brazilian scientific publications, indexed on the Latin American and Caribbean Health Sciences Database, Nursing Database and the International Health Sciences Literature of which the abstract was available online and in Portuguese. Conclusion: it is observed that most publications refer to care givers and their health, which implies a need for further studies that aim at creating a care plan for the elderly with Alzheimer(AU)

Humans , Aged , Aged, 80 and over , Review Literature as Topic , Alzheimer Disease/pathology , Nursing Care/methods , Health Services Administration , Caregivers/education
Full dent. sci ; 6(24): 555-559, set.2015. tab
Article in Portuguese | LILACS | ID: lil-777679


A doença de Alzheimer é uma doença neurodegenerativa que provoca o declínio das funções intelectuais, reduzindo as capacidades de trabalho e relação social, interferindo no comportamento e personalidade do indivíduo. O objetivo deste estudo foi analisar os aspectos relativos às necessidades odontológicas dos pacientes idosos portadores de Alzheimer. Para tanto, foi realizada uma revisão de literatura utilizando as bases de dados, em que os resultados foram divididos em dois tópicos: considerações relativas ao tratamento odontológico e alterações bucais frequentes em pacientes com doença de Alzheimer. Concluiu-se que o cirurgião dentista deve conhecer as características dos pacientes com doença de Alzheimer planejando o tratamento mais adequado, e orientando a equipe de saúde, cuidadores e familiares a fim de ser obter sucesso na implementação de medidas preventivas e curativas...

Alzheimer disease is a neurodegenerative disease that causes the decline of intellectual functions, reducing the capacity for work and social relationships, interfering with the behavior and personality of the individual. The aim of this study was to analyze factors related to dental needs of elderly patients with AlzheimerÆs. Therefore, it was conducted a literature review and the results were divided into two topics: considerations about dental treatment and frequent buccal alterations in patients with AlzheimerÆs. It was concluded that it is important that the dentist knows the characteristics of patients with degenerative diseases in order to develop proper treatment planning, and guide caregivers and family in order to achieve successful adoption of preventive and healing measures...

Humans , Aged , Delivery of Health Care , Alzheimer Disease/pathology , Geriatric Dentistry , Oral Health/education
Arq. neuropsiquiatr ; 73(7): 553-560, 07/2015. tab, graf
Article in English | LILACS | ID: lil-752378


Neuropsychiatric symptoms in Alzheimer’s disease (AD) are prevalent, however their relationship with patterns of cortical atrophy is not fully known. Objectives To compare cortical atrophy’s patterns between AD patients and healthy controls; to verify correlations between neuropsychiatric syndromes and cortical atrophy. Method 33 AD patients were examined by Neuropsychiatric Inventory (NPI). Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI syndromes: affective, apathy, hyperactivity and psychosis. Correlations between structural imaging and neuropsychiatric scores were performed by Freesurfer. Results were significant with a p-value < 0.05, corrected for multiple comparisons. Results Patients exhibited atrophy in entorhinal cortices, left inferior and middle temporal gyri, and precuneus bilaterally. There was correlation between affective syndrome and cortical thickness in right frontal structures, insula and temporal pole. Conclusion Cortical thickness measures revealed atrophy in mild AD. Depression and anxiety symptoms were associated with atrophy of right frontal, temporal and insular cortices. .

Os sintomas neuropsiquiátricos na doença de Alzheimer (DA) são prevalentes, porém suas relações com padrões de atrofia cortical não são totalmente compreendidas. Objetivos Comparar padrões de atrofia cortical entre DA e controles; verificar se há correlações entre sintomas neuropsiquiátricos e atrofia cortical. Método 33 pacientes com DA foram examinados pelo Inventário Neuropsiquiátrico. Os pacientes e 29 controles foram submetidos à RNM. Consideramos quatro síndromes: afetiva, apatia, hiperatividade e psicose. Correlações entre imagens estruturais e os scores foram feitas pelo Freesurfer. Os resultados foram significantes com um valor de p < 0,05, corrigido para múltiplas comparações. Resultados Pacientes exibiram atrofia nos córtices entorrinais, giros temporal médio e inferior esquerdos, e precuneo bilateralmente. Houve correlação entre síndrome afetiva e espessura cortical em estruturais frontais direitas, ínsula e polo temporal. Conclusão Medidas de espessura cortical revelaram atrofia na DA. Sintomas de depressão e ansiedade foram associados à atrofia dos córtices frontal direito, temporal e ínsula. .

Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Alzheimer Disease/pathology , Cerebral Cortex/pathology , Mood Disorders/pathology , Alzheimer Disease/psychology , Anxiety/pathology , Anxiety/psychology , Atrophy/pathology , Atrophy/psychology , Case-Control Studies , Depression/pathology , Depression/psychology , Magnetic Resonance Imaging , Mood Disorders/psychology , Neuropsychological Tests , Psychiatric Status Rating Scales , Reference Values , Syndrome
Braz. j. med. biol. res ; 48(5): 382-391, 05/2015. tab, graf
Article in English | LILACS | ID: lil-744376


Lung cancer often exhibits molecular changes, such as the overexpression of the ErbB1 gene that encodes epidermal growth factor receptor (EGFR). ErbB1 amplification and mutation are associated with tumor aggressiveness and low response to therapy. The aim of the present study was to design a schedule to synchronize the cell cycle of A549 cell line (a non-small cell lung cancer) and to analyze the possible association between the micronuclei (MNs) and the extrusion of ErbB1 gene extra-copies. After double blocking, by the process of fetal bovine serum deprivation and vincristine treatment, MNs formation was monitored with 5-bromo-2-deoxyuridine (BrdU) incorporation, which is an S-phase marker. Statistical analyses allowed us to infer that MNs may arise both in mitosis as well as in interphase. The MNs were able to replicate their DNA and this process seemed to be non-synchronous with the main cell nuclei. The presence of ErbB1 gene in the MNs was evaluated by fluorescent in situ hybridization (FISH). ErbB1 sequences were detected in the MNs, but a relation between the MNs formation and extrusion of amplified ErbB1could not be established. The present study sought to elucidate the meaning of MNs formation and its association with the elimination of oncogenes or other amplified sequences from the tumor cells.

Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Alzheimer Disease , Apolipoproteins E/genetics , Brain/pathology , Cholesterol Ester Transfer Proteins/genetics , Polymorphism, Genetic/genetics , Age Distribution , Atrophy , Alzheimer Disease/epidemiology , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Follow-Up Studies , Genotype , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Magnetic Resonance Imaging , Risk Factors
Mem. Inst. Oswaldo Cruz ; 110(2): 201-208, 04/2015. tab, graf
Article in English | LILACS | ID: lil-744468


Extracellular ATP may act as a danger signalling molecule, inducing inflammation and immune responses in infection sites. The ectonucleotidases NTPDase and ecto-5’-nucleotidase are enzymes that modulate extracellular nucleotide levels; these enzymes have been previously characterised in Trichomonas vaginalis. Iron plays an important role in the complex trichomonal pathogenesis. Herein, the effects of iron on growth, nucleotide hydrolysis and NTPDase gene expression in T. vaginalis isolates from female and male patients were evaluated. Iron from different sources sustained T. vaginalis growth. Importantly, iron from haemoglobin (HB) and haemin (HM) enhanced NTPDase activity in isolates from female patients and conversely reduced the enzyme activity in isolates from male patients. Iron treatments could not alter the NTPDase transcript levels in T. vaginalis. Furthermore, our results reveal a distinct ATP, ADP and AMP hydrolysis profile between isolates from female and male patients influenced by iron from HB and HM. Our data indicate the participation of NTPDase and ecto-5’-nucleotidase in the establishment of trichomonas infection through ATP degradation and adenosine production influenced by iron.

Aged , Aged, 80 and over , Female , Humans , Male , Alzheimer Disease/pathology , Complementary Therapies , Alzheimer Disease/therapy , Disease Progression , Feasibility Studies
Cad. saúde pública ; 31(4): 667-681, 04/2015. tab, graf
Article in Spanish | LILACS | ID: lil-744849


El objetivo del estudio fue determinar la efectividad del ejercicio físico en la fatiga de pacientes con cáncer durante el tratamiento activo. Las bases de datos de PubMed Central, EMBASE y OVID fueron consultadas hasta abril de 2014 para identificar ensayos clínicos aleatorizados, que evaluaran el efecto del ejercicio en la fatiga de pacientes con cáncer sometidos a tratamiento activo. Once estudios (n = 1.407) fueron incluidos. La quimioterapia fue el tratamiento más común (n = 1.028). Los estudios tuvieron bajo riesgo de sesgo y alta calidad metodológica. Las estimaciones de efecto mostraron que el ejercicio físico mejoró significativamente la fatiga (SMD = -3,0; IC95%: -5,21; -0,80), p < 0,0001. Se encontraron efectos similares para el entrenamiento de resistencia (SMD = -4,5; IC95%: -7,24; -1,82), p = 0,001. Se encontraron mejoras significativas en pacientes con cáncer de mama y de próstata (p < 0,05). El ejercicio es una intervención segura y eficaz en el control de la fatiga en pacientes sometidos a tratamiento activo.

This study aimed to determine the effectiveness of physical exercise in decreasing fatigue in cancer patients during active treatment. The PubMed Central, EMBASE, and OVID databases were consulted up to April 2014 to identify randomized clinical trials that evaluated the effect of exercise on fatigue in cancer patients undergoing active treatment. Eleven studies (n = 1,407) were included. Chemotherapy was the most common form of treatment (n = 1,028). The studies showed a low risk of bias and high methodological quality. Effect estimates showed that physical exercise significantly improved fatigue (SMD = -3.0; 95%CI: -5.21; -0.80), p < 0.0001. Similar effects were found for resistance training (SMD = -4.5; 95%CI: -7.24; -1.82), p = 0.001. Significant improvements were found in breast and prostate cancer patients (p < 0.05). Exercise is a safe and effective intervention in the management fatigue in cancer patients undergoing active treatment.

O objetivo foi determinar a efetividade do exercício físico sobre a fadiga em pacientes com câncer durante o tratamento ativo. As bases de dados PubMed Central, EMBASE e OVID foram consultadas até abril de 2014 para identificar ensaios clínicos randomizados que avaliaram o efeito do exercício sobre a fadiga em pacientes com câncer em tratamento ativo. Onze estudos (n = 1.407) foram incluídos. A quimioterapia foi o tratamento mais comum (n = 1.028). Os estudos tiveram baixo risco de viés e alta qualidade metodológica. As estimativas de efeito mostraram que o exercício melhorou significativamente a fadiga (DMP = -3,0; IC95%: -5,21; -0,80), p < 0,0001. Efeitos semelhantes sobre o treinamento de resistência (DMP = -4,5; IC95%: -7,24; -1,82), p = 0,001 foram encontrados. O exercício físico é uma intervenção segura e eficaz contra a fadiga em pacientes submetidos ao tratamento ativo.

Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Alzheimer Disease/pathology , Corpus Callosum/pathology , Image Interpretation, Computer-Assisted/methods , Logistic Models , Magnetic Resonance Imaging
Acta cir. bras ; 30(3): 165-169, 03/2015. tab, graf
Article in English | LILACS | ID: lil-741037


PURPOSE: To evaluate the effect of fasting on gastric emptying in mice. METHODS: Twenty-eight mice were distributed into three study groups: a normal group (N=4): normal standard animals; a total fasting group (N=12): subjected to food and water deprivation and a partial fasting group (N=12): subjected to food deprivation only. The fasting groups were subdivided into three subgroups of four animals each, according to the date of euthanasia: 24, 48 and 72 hours. Was analyzed: the gastric volume, degree of the gastric wall distention and the presence of food debris in gastrointestinal tract. RESULTS: The mean gastric volume was 1601 mm3in the normal group, 847 mm3in total fasting group and 997 mm3in partial fasting group. There was difference between the fasting groups in any analyzed period (p<0.05). Regarding the presence of food debris in the gastrointestinal tract and the degree of distension of the stomach, there was no difference between the groups that underwent total or partial fasting (p>0.05). CONCLUSION: Total fasting or only-solids deprivation does not induce gastric emptying in mice. .

Aged , Female , Humans , Male , Aging/pathology , Alzheimer Disease/pathology , Brain/pathology , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Cognitive Dysfunction/pathology , Algorithms , Alzheimer Disease/complications , Computer Simulation , Diagnosis, Differential , Models, Statistical , Multivariate Analysis , Cognitive Dysfunction/complications , Pattern Recognition, Automated/methods , Reference Values , Reproducibility of Results , Sensitivity and Specificity
Article in Korean | WPRIM | ID: wpr-69479


PURPOSE: The purpose of this study was to evaluate the psychometric properties of the Korean version of the Alzheimer's Disease Knowledge Scale (ADKS-K) to determine its applicability to Korean adults. METHODS: Cross-cultural validity was performed according to Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN). The Kuder-Richardson Formula 20 for internal consistency and Intraclass Correlation Coefficient (ICC) for test-retest reliability were conducted. Content validity, criterion related validity and construct validity were evaluated. The Classical Test Theory (CTT) model and the Item Response Theory (IRT) model were applied in performing the item analysis. RESULTS: The KR 20 was .71, and the ICC was .90, indicating that the ADKS-K has internal consistency and stability reliability. Thirty items of the ADKS-K had significant Content Validity Ratio (CVR) values, i.e., mean of 0.82 and range of 0.60~1.00. Mean item difficulty and discrimination indices calculated by TestAn program were 0.63 and 0.23, respectively. Mean item difficulty and discrimination indices calculated by BayesiAn program were -0.60 and 0.77, respectively. These tests indicate that ADKS-K has an acceptable level of difficulty and discriminating efficiency. CONCLUSION: Results suggest that ADKS-K has the potential to be a proper instrument for assessing AD knowledge in Korean adults.

Adult , Alzheimer Disease/pathology , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Nursing Staff/psychology , Psychometrics , Republic of Korea , Surveys and Questionnaires , Translating , Young Adult
Trends psychiatry psychother. (Impr.) ; 36(3): 160-168, Jul-Sep/2014. tab, graf
Article in English | LILACS | ID: lil-724120


INTRODUCTION: Cognitive reserve (CR), a hypothetical construct used to obtain information about cognitive aging, describes the capacity of the adult brain to cope with the effects of neurodegenerative processes. This study evaluated CR using a CR questionnaire (CRQ) and a set of variables (education, leisure activities, lifelong occupation) that inform CR. It also developed a CR index, validated the CRQ, and examined the correlation between the different CR measures. METHODS: Functional and neuropsychological capacities of 75 outpatients (mean age: 80.2 years) with a probable AD diagnosis were evaluated. Socio-demographic data and clinical variables were collected. Patients completed two questionnaires: the Participation in Leisure Activities throughout Life questionnaire, and the CRQ. RESULTS: Participants with a greater CR had higher scores in cognitive tests than the elderly with a lower CR. A CR index was developed. CRQ reliability was 0.795 (Cronbach's alpha). There was a close association between the CR Index and the CRQ. CONCLUSIONS: This study found an association between CR measures and education, occupation and participation in leisure activities. The CRQ seems to be a suitable instrument to measure CR in Portuguese populations (AU)

INTRODUÇÃO: A reserva cognitiva (RC), um construto usado para informar sobre o envelhecimento cognitivo, descreve a capacidade do cérebro adulto em lidar com os efeitos de processos neurodegenerativos. Este estudo teve como objetivos avaliar a RC com o Questionário de RC (QRC) e através de variáveis (escolaridade, actividades de lazer, ocupação ao longo da vida) que informam sobre a RC; desenvolver um índice de RC; validar o QRC; e correlacionar as diferentes medidas de RC. MÉTODOS: Foram avaliadas as capacidades funcionais e neuropsicológicas de 75 doentes (idade média: 80,2 anos) com diagnóstico de provável doença de Alzheimer, seguidos em ambulatório. Os dados recolhidos incluíram variáveis sócio-demográficas e clínicas. Os pacientes completaram dois questionários: Participação em Atividades de Lazer ao Longo da Vida; e QCR. RESULTADOS: Os doentes com os níveis mais elevados de RC obtiveram os valores mais elevados nos testes cognitivos. Neste estudo foi desenvolvido um IRC. O QRC (versão portuguesa) teve uma fidelidade de 0,795 (alpha de Cronbach) e foi demonstrada uma associação alta entre o IRC e o QRC. CONCLUSÕES: Verificou-se a existência de uma associação entre as medidas de RC e a escolaridade, ocupação e participação em atividades de lazer. O CRQ pode ser considerado um instrumento adequado para medir o CR da população portuguesa (AU)

Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Aging/psychology , Alzheimer Disease/psychology , Cognitive Reserve , Aging/pathology , Alzheimer Disease/pathology , Cross-Sectional Studies , Dementia/diagnosis , Health Status Indicators , Leisure Activities/psychology , Life Style , Social Class , Surveys and Questionnaires/standards , Validation Study
Medicina (B.Aires) ; 74(4): 282-286, ago. 2014. ilus, graf
Article in Spanish | LILACS | ID: lil-734386


Existen múltiples evidencias de alteraciones neuronales y gliales en etapas avanzadas de la enfemedad de Alzheimer con abundantes depósitos cerebrales de beta amiloide, aunque hay pocos datos de cambios tempranos que podrían contribuir al desarrollo de la enfermedad. Evaluamos alteraciones morfológicas neuronales y gliales, y cambios cognitivos y emocionales tempranos en ratones transgénicos PDAPP-J20 (Tg), portadores del gen humano de APP (amyloid precursor protein) mutado, a los 5 meses de edad, aún sin depósitos amiloides en el hipocampo y con niveles bajos de péptidos amiloides cerebrales. Mediante inmunohistoquímica para NeuN, los Tg presentaron menor número de neuronas piramidales y granulares en el hipocampo, junto con un menor volumen de la estructura, en comparación con los controles no transgénicos. La neurogénesis se encontró afectada, evidenciada por reducido número de neuronas DCX+ en el giro dentado. En la región CA3, hubo una menor densidad de sinaptofisina sugiriendo alteraciones sinápticas entre neuronas granulares y piramidales, sin cambios en la densidad de espinas dendríticas en CA1. Utilizando microscopía confocal, observamos una disminución del número de astrocitos GFAP+ con una reducción de la complejidad celular, sugiriendo atrofia glial. Se detectó un déficit cognitivo (reconocimiento de localización novedosa de un objeto) y un aumento de la ansiedad (campo abierto) en los Tg, con aumento en los núcleos c-Fos+ en amígdala, evidenciando el papel de la emocionalidad en los inicios de la enfermedad. El estudio de las alteraciones iniciales en la enfermedad amiloide podría contribuir al desarrollo de métodos de diagnóstico temprano y de terapéutica preventiva.

Although there is strong evidence about neuronal and glial disturbances at advanced stages of Alzheimer’s disease, less attention has been directed to early, pre-amyloid changes that could contribute to the progression of the disease. We evaluated neuronal and glial morphological changes and behavioral disturbances in PDAPP-J20 transgenic (Tg) mice, carrying mutated human APP gene (amyloid precursor protein), at 5 months of age, before brain amyloid deposition occurs. Using NeuN immunohistochemistry we found decreased numbers of pyramidal and granular neurons in the hippocampus associated with a reduction of hippocampal volume in Tg mice compared with controls. Neurogenesis was impaired, evidenced by means of DCX immunohistochemistry in the dentate gyrus. In the CA3 region we found a decreased density of synaptophysin, suggesting synaptic disturbance, but no changes were found in CA1 synaptic spine density. Using confocal microscopy we observed decreased number and cell complexity of GFAP+ astrocytes, indicating potential glial atrophy. Cognitive impairment (novel location recognition test) and increased anxiety (open field) were detected in Tg mice, associated with more c-Fos+ nuclei in the amygdala, possibly indicating a role for emotionality in early stages of the disease. The study of early alterations in the course of amyloid pathology could contribute to the development of diagnostic and preventive strategies.

Animals , Humans , Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/genetics , Disease Models, Animal , Hippocampus/pathology , Cognitive Dysfunction/pathology , Plaque, Amyloid/pathology , Amyloid beta-Protein Precursor/metabolism , Anxiety Disorders/pathology , Astrocytes/pathology , Disease Progression , Dentate Gyrus/metabolism , Mice, Transgenic , Cognitive Dysfunction/genetics , Cognitive Dysfunction/metabolism , Neurogenesis/physiology , Neurons/pathology , Synaptophysin/isolation & purification
Indian J Exp Biol ; 2013 Dec; 51(12): 1086-1093
Article in English | IMSEAR | ID: sea-150296


Nitric oxide plays a role in a series of neurobiological functions, underlying behaviour and memory. The functional role of nNOS derived nitric oxide in cognitive functions is elusive. The present study was designed to investigate the effect of specific neuronal nitric oxide synthase inhibitor, 7-nitroindazole, against intracerebroventricular streptozotocin-induced cognitive impairment in rats. Learning and memory behaviour was assessed using Morris water maze and elevated plus maze. 7-nitroindazole (25 mg/kg, ip) was administered as prophylactically (30 min before intracerebroventricular streptozotocin injection on day 1) and therapeutically (30 min before the assessment of memory by Morris water maze on day 15). Intracerebroventricular streptozotocin produced significant cognitive deficits coupled with alterations in biochemical indices.These behavioural and biochemical changes were significantly prevented by prophylactic treatment of 7-nitroindazole. However, therapeutic intervention of 7-nitroindazole did not show any significant reversal. The results suggests that 7-nitroindazole can be effective in the protection of dementiainduced by intracerebroventricular streptozotocin only when given prophylactically but not therapeutically.

Alzheimer Disease/chemically induced , Alzheimer Disease/enzymology , Alzheimer Disease/pathology , Animals , Cognition Disorders/chemically induced , Cognition Disorders/enzymology , Cognition Disorders/pathology , Enzyme Inhibitors/administration & dosage , Humans , Indazoles/administration & dosage , Male , Maze Learning/drug effects , Maze Learning/physiology , Neurons/metabolism , Neurons/pathology , Nitric Oxide/metabolism , Nitric Oxide Synthase Type I/antagonists & inhibitors , Nitric Oxide Synthase Type I/metabolism , Rats , Streptozocin/toxicity
Psicofarmacologia (B. Aires) ; 13(83): 18-22, nov. 2013. ilus
Article in Spanish | LILACS | ID: lil-726075


La acumulación de amiloide, la edad y la enfermedad vascular son los principales factores de riesgo para desarrollar una demencia. Existe un interjuego entre los factores genéticos y vasculares para desarrollar la enfermedad de Alzheimer de inicio tardío. La activación sostenida del sistema renina Angiotensina parece ocupar un papel destacado en la fisiopatología de las demencias incluyendo la enfermedad de Alzheimer. El tratamiento antihipertensivo con inhibidores de la enzima de conversión de Angiotensina tanto como el bloqueo de los receptores de la Angiotensina II, parecen superiores sobre otros fármacos en la prevención de las demencias

The age, aggregation of amyloid, and vascular disease are major risk factors for developing dementia. There is interplay between genetic and vascular factors to develop late-onset Alzheimer's disease. Sustained the renin angiotensin system activation seems to occupy an important role in the pathophysiology of dementia including Alzheimer's disease. Antihypertensive treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockade, seem superior over other drugs in the prevention of dementia

Humans , Amyloid , Angiotensin II/therapeutic use , Dementia/therapy , Cognitive Dysfunction/pathology , Alzheimer Disease/pathology , Hypertension/pathology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Risk Factors , Renin-Angiotensin System/physiology