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Article in English | WPRIM | ID: wpr-880327


BACKGROUND@#Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring.@*METHODS@#Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting.@*RESULTS@#There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment.@*CONCLUSIONS@#The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.

Animals , Cytoskeletal Proteins/metabolism , Female , Gene Expression Regulation , Hippocampus/metabolism , Insulin-Like Growth Factor II/metabolism , Learning , Learning Disabilities/psychology , Male , Memory Disorders/psychology , Nerve Tissue Proteins/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/psychology , Random Allocation , Rats , Rats, Wistar , Social Environment , Stress, Psychological/genetics
Braz. j. med. biol. res ; 51(6): e6997, 2018. graf
Article in English | LILACS | ID: biblio-889113


MicroRNAs (miRNAs) have been reported to be associated with heart valve disease, which can be caused by inflammation. This study aimed to investigate the functional impacts of miR-27a on TNF-α-induced inflammatory injury in human mitral valve interstitial cells (hMVICs). hMVICs were subjected to 40 ng/mL TNF-α for 48 h, before which the expressions of miR-27a and NELL-1 in hMVICs were altered by stable transfection. Trypan blue staining, BrdU incorporation assay, flow cytometry detection, ELISA, and western blot assay were performed to detect cell proliferation, apoptosis, and the release of proinflammatory cytokines. We found that miR-27a was lowly expressed in response to TNF-α exposure in hMVICs. Overexpression of miR-27a rescued hMVICs from TNF-α-induced inflammatory injury, as cell viability and BrdU incorporation were increased, apoptotic cell rate was decreased, Bcl-2 was up-regulated, Bax and cleaved caspase-3/9 were down-regulated, and the release of IL-1β, IL-6, and MMP-9 were reduced. NELL-1 was positively regulated by miR-27a, and NELL-1 up-regulation exhibited protective functions during TNF-α-induced cell damage. Furthermore, miR-27a blocked JNK and Wnt/β-catenin signaling pathways, and the blockage was abolished when NELL-1 was silenced. This study demonstrated that miR-27a overexpression protected hMVICs from TNF-α-induced cell damage, which might be via up-regulation of NELL-1 and thus modulation of JNK and Wnt/β-catenin signaling pathways.

Humans , Male , Female , Adult , Middle Aged , Inflammation/chemically induced , MicroRNAs/metabolism , Mitral Valve/drug effects , Nerve Tissue Proteins/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Apoptosis , Cell Proliferation , Cell Survival , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Heart Valve Diseases/prevention & control , Inflammation/pathology , Mitral Valve/cytology , Mitral Valve/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Up-Regulation
Biol. Res ; 50: 18, 2017. tab, graf
Article in English | LILACS | ID: biblio-838969


BACKGROUND: Cocaine- and amphetamine-regulated transcript (CART), discovered initially by via differential display RT-PCR analysis of brains of rats administered cocaine, is expressed mainly in central nervous system or neuronal origin cells, and is involved in a wide range of behaviors, such as regulation of food intake, energy homeostasis, and reproduction. The hens egg-laying rate mainly depends on the developmental status of follicles, expression of CART have not been identified from hen follicles, the regulatory mechanisms of CART biological activities are still unknown. The objective of this study was to characterize the mRNA expression of CART in hen follicular granulosa cells and determine CART peptide localization and regulatory role during follicular development. METHODS: Small white follicles (1-2 mm in diameter) were treated for RNA isolation; Small white follicles (1-2 mm in diameter) and large white follicles (4-6 mm in diameter) were treated for immunohistochemical localization and large white follicles (4-6 mm in diameter), small yellow follicles (6-8 mm in diameter), large yellow follicles (9-12 mm in diameter), mature follicles (F5, F4, F3, F2, F1, >12 mm in diameter) were treated for RNA isolation and Real time PCR. RESULTS: The results showed that full length of the CDS of hen CART was 336 bp encoding a 111 amino acid polypeptide. In the hen ovary, CART peptide was primarily localized to the theca layer, but not all, the oocyte and granulosa layer, with diffused, weaker staining than relative to the theca cell layer. Further, amount of CART mRNA was more (P < 0.05) in granulosa cells of 6-8 mm follicles compared with that in granulosa cells of other follicles. However, CART mRNA amount was greater in theca cells of 4-6 mm follicles relative to follicles of other sizes (P < 0.05). CONCLUSIONS: Results suggest that CART could play a potential role in developmental regulation of chicken follicles.

Animals , Female , Ovarian Follicle/metabolism , Nerve Tissue Proteins/metabolism , Immunohistochemistry , Cells, Cultured , Chickens , DNA, Complementary/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Gene Expression Profiling , Nerve Tissue Proteins/genetics
Braz. oral res. (Online) ; 30(1): e109, 2016. tab, graf
Article in English | LILACS | ID: biblio-952054


Abstract Multicystic and unicystic ameloblastomas are benign odontogenic tumors that present distinct biological behavior. The investigation of stem cells has become an important branch of tumor biology, with several studies addressing the possible role of these cells in tumor growth, angiogenesis, progression, infiltration and invasiveness. This study evaluated the immunohistochemical expression of CD90(Thy-1) and P75NTR stem cell markers in multicystic and unicystic ameloblastomas. Seventeen (17) samples of ameloblastomas (multicystic, n = 10; unicystic, n = 7) were submitted to immunohistochemical reactions and graded semi-quantitatively. The Kolmogorov-Smirnov test was used to verify possible differences in CD90 and P75NTR expressions between multicystic and unicystic ameloblastomas (p < 0.05). CD90 immunostaining was observed in all multicystic ameloblastoma specimens (n = 10), in the cytoplasm of the fibroblasts and vascular endothelial cells of the tumor stroma, near the neoplastic odontogenic epithelia. The staining of stromal CD90 was significantly higher in multicystic than in unicystic ameloblastomas (p = 0.003). Nuclear P75NTR immunostaining was observed in all ameloblastoma specimens. A significant difference was seen in the epithelial staining of P75NTR between multicystic and unicystic types (p = 0.007). The increased expression of CD90 and P75NTR found in multicystic ameloblastomas suggests a behavioral biological difference between multicystic and unicystic ameloblastomas, as well as a difference in ameloblastoma development.

Humans , Male , Female , Adolescent , Adult , Young Adult , Neoplastic Stem Cells/metabolism , Ameloblastoma/metabolism , Mandibular Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Receptors, Nerve Growth Factor/metabolism , Thy-1 Antigens/metabolism , Nerve Tissue Proteins/metabolism , Neoplastic Stem Cells/pathology , Immunohistochemistry , Ameloblastoma/pathology , Mandibular Neoplasms/pathology , Paraffin Embedding , Stromal Cells , Statistics, Nonparametric , Endothelial Cells/metabolism , Fibroblasts/metabolism , Middle Aged
Rev. bras. anestesiol ; 65(3): 213-217, May-Jun/2015. graf
Article in English | LILACS | ID: lil-748915


BACKGROUND AND OBJECTIVES: This study shows how the diffusion of the anesthetic into the sheath occurs through the axillary infraclavicular space and hence proves the efficacy of the anesthetic block of the brachial plexus, and may thereby allow a consolidation of this pathway, with fewer complications, previously attached to the anesthesia. MATERIALS AND METHODS: 33 armpits of adult cadavers were analyzed and unfixed. We injected a solution of neoprene with latex dye in the infraclavicular space, based on the technique advocated by Gusmão et al., and put the corpses in refrigerators for three weeks. Subsequently, the specimens were thawed and dissected, exposing the axillary sheath along its entire length. RESULTS AND DISCUSSION: Was demonstrated involvement of all fasciculus of the plexus in 51.46%. In partial involvement was 30.30%, 18.24% of cases the acrylic was located outside the auxiliary sheath involving no issue. CONCLUSIONS: The results allow us to establish the infraclavicular as an effective and easy way to access plexus brachial, because the solution involved the fascicles in 81.76% partially or totally, when it was injected inside the axillary sheath. We believe that only the use of this pathway access in practice it may demonstrate the efficiency. .

JUSTIFICATIVA E OBJETIVOS: Procuramos demonstrar como ocorre a difusão do anestésico no interior da bainha axilar, quando se utiliza o bloqueio por via infraclavicular, através da fossa infraclavicular e, consequentemente, provar a eficácia dessa via, podendo, com isso, permitir uma consolidação da utilização desse acesso, com redução das complicações. MATERIAS E MÉTODO: Foram utilizadas 33 axilas de cadáveres adultos não fixados. Injetamos uma solução de neoprene látex com corante na fossa infraclavicular, baseando-se na técnica preconizada por Gusmão e col, e colocamos os cadáveres em geladeiras por três semanas. Posteriormente, as peças foram descongeladas e dissecadas, expondo a bainha axilar em toda sua extensão. RESULTADOS E DISCUSSÃO: Foi demonstrado envolvimento de todos os fascículos do plexo em 51,46%. Em 30,30% houve envolvimento parcial, e em 18,24% dos casos o acrílico foi localizado fora da bainha axilar, não envolvendo nenhum fascículo. CONCLUSÕES: Os dados obtidos permitem estabelecer a via infraclavicular como uma via eficaz e de fácil acesso ao plexo braquial, visto que a solução injetada envolveu os fascículos em 81,76% parcialmente ou totalmente, quando era injetada dentro da bainha axilar. Acreditamos que apenas a utilização desta via de acesso na prática poderá demonstrar a eficiência da mesma. .

JUSTIFICACIÓN Y OBJETIVOS: Este estudio intenta demostrar cómo ocurre la difusión del anestésico en el interior de la vaina axilar, cuando se utiliza el bloqueo por vía infraclavicular a través de la fosa infraclavicular, y al mismo tiempo, probar la eficacia de esa vía, pudiendo así permitir una consolidación de la utilización de ese acceso con reducción de las complicaciones. MATERIALES Y MÉTODO: Fueron utilizadas 33 axilas de cadáveres adultos no fijadas. Inyectamos una solución de neopreno látex con colorante en la fosa infraclavicular, con la técnica preconizada por Gusmão et al., y colocamos los cadáveres en frigoríficos durante 3 semanas. Posteriormente, las piezas fueron descongeladas y disecadas, exponiendo la vaina axilar en toda su extensión. RESULTADOS Y DISCUSIÓN: Quedó demostrada la implicación de todos los fascículos del plexo en un 51,46%. En un 30,30% hubo una participación parcial, y en un 18,24% de los casos el acrílico fue ubicado fuera de la vaina axilar sin la participación de ningún fascículo. CONCLUSIONES: Los datos obtenidos permiten establecer la vía infraclavicular como una vía eficaz y de fácil acceso al plexo braquial, visto que la solución inyectada tuvo la participación de los fascículos en un 81,76% parcial o totalmente, cuando se inyectaba dentro de la vaina axilar. Creemos que solamente con la utilización de esta vía de acceso en la práctica podrá quedar demostrada su eficacia. .

Animals , Male , Action Potentials/physiology , Cerebellar Cortex/physiology , Cerebellar Cortex/cytology , Nerve Tissue Proteins/metabolism , Purkinje Cells/physiology , Staining and Labeling , TRPC Cation Channels/metabolism
Salud colect ; 11(1): 99-114, ene.-mar. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-746687


El Consejo Federal de Medicina de Brasil (CFM) -órgano normativo y fiscalizador del ejercicio ético de la medicina- prohibió, en 2008, la participación de médicos brasileños en investigaciones que utilizaran placebo para enfermedades con tratamiento eficaz y efectivo, en contraposición a la Declaración de Helsinki, que permite su uso en condiciones metodológicamente justificadas. Con el objetivo de verificar si la normativa ética del CFM modificó el uso de placebo en ensayos clínicos de fase III en Brasil, se analizaron varias características de sus registros en el, en los períodos de 2003 a 2007 y de 2009 a 2013. Se concluye que: a) la normativa promulgada por el CFM en 2008 fue ineficaz y prevaleció la posición adoptada por la Declaración de Helsinki; b) el patrocinio de ensayos con placebo por parte de la industria farmacéutica multinacional fue significativo; c) predominaron las investigaciones de fármacos para enfermedades crónicas, y fueron poco significativas para las enfermedades postergadas, de importancia para Brasil.

In 2008, Brazil's Federal Council of Medicine [Conselho Federal de Medicina] (CFM) - regulatory and supervisory agency on the ethical practice of medicine - banned the participation of Brazilian doctors in studies using placebos for diseases with efficient and effective treatment. This position differs with the Helsinki Declaration, which allows the use of placebos in methodologically justified conditions. To ascertain whether the CMF's ethical regulation modified the use of placebos in phase III clinical trials in Brazil, characteristics of the records in were researched in the periods from 2003 to 2007 and from 2009 to 2013. The conclusions reached were: a) the regulations issued by the CFM in 2008 were ineffective and the position adopted by the Helsinki Declaration prevails; b) there was significant sponsorship by the multinational pharmaceutical industry of trials with placebos; c) the research was predominantly on new drugs for chronic diseases, with little study done of the neglected diseases which are of great importance to Brazil.

Animals , Rats , Apoptosis/genetics , Gene Expression Regulation, Enzymologic/genetics , Heme/deficiency , Nerve Degeneration/genetics , Neurons/metabolism , Porphyrias/complications , Apoptosis/drug effects , Caspases/drug effects , Caspases/metabolism , Cell Survival/drug effects , Cell Survival/genetics , Collagen Type XI/drug effects , Collagen Type XI/metabolism , Cyclic AMP Response Element-Binding Protein/drug effects , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Down-Regulation/drug effects , Down-Regulation/physiology , Enzyme Inhibitors , Gene Expression Regulation, Enzymologic/drug effects , Heptanoates , Heme/biosynthesis , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Membrane Proteins/drug effects , Membrane Proteins/genetics , Membrane Proteins/metabolism , Nerve Degeneration/metabolism , Nerve Degeneration/physiopathology , Nerve Tissue Proteins/drug effects , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neural Cell Adhesion Molecules/drug effects , Neural Cell Adhesion Molecules/genetics , Neural Cell Adhesion Molecules/metabolism , Neurons/drug effects , Neurons/pathology , Poly(ADP-ribose) Polymerases , Porphyrias/metabolism , Porphyrias/physiopathology , RNA, Messenger/drug effects , RNA, Messenger/metabolism , RNA-Binding Proteins/drug effects , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , SMN Complex Proteins , Up-Regulation/drug effects , Up-Regulation/physiology , Vesicular Transport Proteins/drug effects , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/metabolism
Rev. bras. epidemiol ; 18(1): 194-207, Jan-Mar/2015. tab
Article in Portuguese | LILACS | ID: lil-736436


OBJETIVO: Analisar os fatores pessoais associados à prevalência e duração dos benefícios auxílio-doença decorrentes de sinovite e tenossinovite (CID10 M65). MÉTODO: Estudo transversal referente aos benefícios auxílio-doença decorrentes de sinovite e tenossinovite concedidos pelo Instituto Nacional de Seguro Social aos empregados no Brasil em 2008. Dados sobre o ramo de atividade econômica (Classificação Nacional de Atividades Econômicas - CNAE divisão, classe), sexo, idade, espécie e duração dos benefícios foram coletados do Sistema Único de Benefícios. A população corresponde à média mensal dos vínculos empregatícios declarados ao Cadastro Nacional de Informações Sociais. RESULTADOS: Em 2008 foram concedidos 35.601 benefícios auxílio-doença decorrentes de sinovite e tenossinovite, com prevalência de 10,9/10.000 vínculos empregatícios. No conjunto dos benefícios auxílio-doença houve maior razão de prevalência (RP) acidentária (RP 1,2), sendo esta maior em mulheres (RP 3,3), e em trabalhadores com idade acima de 39 anos (RP 1,4). As CNAE 37-Esgoto (55,4) e 60-Atividade de rádio e TV (47,1) apresentaram as maiores prevalências, no entanto, 64-Atividade de serviços financeiros e 6422-Bancos múltiplos caracterizaram mais acidentes de trabalho (RP 3,2 e 3,8, respectivamente) e maior duração (70 e 73 dias, respectivamente). A maior duração de benefício ocorreu entre trabalhadores com idade superior a 39 anos. Tanto a CNAE-divisão 60-Atividade de rádio e TV, quanto a CNAE-classe 6010-Atividade de rádio apresentaram elevadas razões de feminilidade (RP 8,1 e 10,8, respectivamente). CONCLUSÃO: A incapacidade para o trabalho por sinovite e tenossinovite apresenta associação tanto da prevalência quanto da duração com o ramo de atividade, sexo, idade e espécie de benefício (previdenciário/acidentário). .

OBJECTIVE: To analyse the personal and occupational factors associated with the prevalence and duration of sickness benefit claims due to synovitis and tenosynovitis (CID10 M65). METHODS: Cross-sectional study regarding sickness benefit claims due to synovitis and tenosynovitis granted to employees by National Institute of Social Security in Brazil in 2008. Data on economic activity (Economic Activities National Classification - CNAE division, class), sex, age, type and duration of benefits were collected from the Unified Benefit System. The study's population consists of the average monthly employment contracts declared to the National Register of Social Information. RESULTS: In 2008, 35,601 employees were granted sickness benefits due to synovitis and tenosynovitis, with a prevalence of 10.9/10,000 employments. Sickness benefits showed higher prevalence rates (PR) for work-related claims (PR 1,2), mostly made by females (PR 3.3) and by workers older than 39 years (PR 1,4). The CNAE 37-Sewage (55.4) and 60-Broadcasting Activity (47.1) had the highest overall prevalence. However, the 64-Financial service activities, except insurance and pension funding and 6422-Multiple banks with commercial service had the highest rates of work-related claims (RP 3.2 and 3.8, respectively), and the longer duration (70 and 73 days, respectively). Workers older than 39 years had the highest durations of work disability claims. Both the CNAE-division 60-Broadcasting Activity, and the CNAE-class 6010-Radio showed a high activity ratio of females (PR 8.1 and 10.8, respectively). CONCLUSION: The work disability due to synovitis and tenosynovitis presents prevalence and duration associated with economic activity, sex, age and kind of benefit (non work-related and work-related claims). .

Humans , Globins/chemistry , Hydrogen Peroxide/chemistry , Nerve Tissue Proteins/chemistry , Nitrites/chemistry , Amino Acid Sequence , Binding Sites , Catalysis , Cysteine/chemistry , Cysteine/metabolism , Disulfides/chemistry , Disulfides/metabolism , Globins/metabolism , Hydrogen Peroxide/metabolism , Kinetics , Models, Molecular , Molecular Sequence Data , Myoglobin/chemistry , Myoglobin/metabolism , Nerve Tissue Proteins/metabolism , Nitrites/metabolism , Oxidation-Reduction , Protein Conformation , Phenol/chemistry , Phenols/chemistry , Phenylacetates/chemistry , Tandem Mass Spectrometry
Colomb. med ; 46(1): 19-25, Jan.-Mar. 2015. ilus
Article in English | LILACS | ID: lil-753531


Background: Prefrontal cortex (PFC) represents the highest level of integration and control of psychic and behavioral states. Several dysfunctions such as autism, hyperactivity disorders, depression, and schizophrenia have been related with alterations in the prefrontal cortex (PFC). Among the cortical layers of the PFC, layer II shows a particular vertical pattern of organization, the highest cell density and the biggest non-pyramidal/pyramidal neuronal ratio. We currently characterized the layer II cytoarchitecture in human areas 10, 24, and 46. Objective: We focused particularly on the inhibitory neurons taking into account that these cells are involved in sustained firing (SF) after stimuli disappearance. Methods: Postmortem samples from five subjects who died by causes different to central nervous system diseases were studied. Immunohistochemistry for the neuronal markers, NeuN, parvalbumin (PV), calbindin (CB), and calretinin (CR) were used. NeuN targeted the total neuronal population while the rest of the markers specifically the interneurons. Results: Cell density and soma size were statically different between areas 10, 46, 24 when using NeuN. Layer II of area 46 showed the highest cell density. Regarding interneurons, PV+-cells of area 46 showed the highest density and size, in accordance to the proposal of a dual origin of the cerebral cortex. Interhemispheric asymmetries were not identified between homologue areas. Conclusion: First, our findings suggest that layer II of area 46 exhibits the most powerful inhibitory system compared to the other prefrontal areas analyzed. This feature is not only characteristic of the PFC but also supports a particular role of layer II of area 46 in SF. Additionally, known functional asymmetries between hemispheres might not be supported by morphological asymmetries.

Antecedentes: La corteza prefrontal (CPF) representa el nivel más alto de integración y control de funciones psíquicas y comportamentales. Varias patologías como autismo, desórdenes de hiperactividad, depresión y esquizofrenia se han relacionado con alteraciones de la CPF. La lámina II de las áreas que constituyen la CPF posee un patrón de organización vertical, una alta densidad celular y la mayor proporción de neuronas no-piramidal/piramidal. Sin embargo, la distribución del componente inhibitorio en estas regiones no se ha descrito. Objetivo: En el presente estudio nos propusimos caracterizar la lámina II de las áreas 10, 24 y 46 del humano, particularmente su componente inhibitorio teniendo en mente su participación en procesos de actividad sostenida relevantes cuando desaparece el estímulo. Métodos: Se utilizaron muestras de cinco sujetos que fallecieron por causas diferentes a enfermedades del sistema nervioso. Se tomaron secciones de las áreas 10, 24 y 46 de Brodmann y se procesaron con los anticuerpos contra NeuN para determinar la población neuronal total y contra Parvalbumina (PV), Calbindina (CB) y Calretinina (CR) para analizar la población de interneuronas. Resultados: Los resultados no mostraron diferencias interhemisféricas entre las áreas. Sin embargo, las tres áreas seleccionadas son significativamente diferentes entre sí en todos los parámetros analizados. El área 46 posee la mayor densidad y tamaño de interneuronas positivas para PV. Conclusiones: La ausencia de asimetrías morfológicas no permite explicar las asimetrías funcionales. La lámina II del área 46 posee el sistema inhibitorio más poderoso. Teniendo en cuenta la arquitectura modular de las capas supragranulares, este sistema inhibitorio subyace a la actividad sostenida, eje fundamental de la memoria operativa.

Adult , Humans , Male , Middle Aged , Interneurons/cytology , Neurons/metabolism , Prefrontal Cortex/cytology , Antigens, Nuclear/metabolism , /metabolism , Calbindins/metabolism , Nerve Tissue Proteins/metabolism , Parvalbumins/metabolism
Cad. saúde pública ; 31(3): 477-486, 03/2015.
Article in English | LILACS | ID: lil-744826


This paper offers a critical overview of social science research presented at the 2014 International AIDS Conference in Melbourne, Australia. In an era of major biomedical advance, the political nature of HIV remains of fundamental importance. No new development can be rolled out successfully without taking into account its social and political context, and consequences. Four main themes ran throughout the conference track on social and political research, law, policy and human rights: first, the importance of work with socially vulnerable groups, now increasingly referred to as "key populations"; second, continued recognition that actions and programs need to be tailored locally and contextually; third, the need for an urgent response to a rapidly growing epidemic of HIV among young people; and fourth, the negative effects of the growing criminalization of minority sexualities and people living with HIV. Lack of stress on human rights and community participation is resulting in poorer policy globally. A new research agenda is needed to respond to these challenges.

Este artigo oferece uma perspectiva crítica da pesquisa em ciências sociais apresentada na Confe-rência Internacional de AIDS de Melbourne, Aus-trália, em 2014. Em tempos de grandes avanços no campo biomédico, a natureza política do HIV permanece de importância fundamental. Nenhuma inovação será bem-sucedida na prática se desconsiderar o contexto sociopolítico e suas consequências. Quatro temas emergiram da Conferência nos campos do direito, dos direitos humanos e da pesquisa social e política: (1) a importância do trabalho com grupos socialmente vulneráveis, crescentemente chamado de "populações chaves"; (2) o reconhecimento de que ações e programas devem ser sob medida para cada local e contexto; (3) a urgência da resposta a uma epidemia crescendo muito rapidamente entre adolescentes; (4) o efeito negativo da crescente criminalização de minorias sexuais e pessoas vivendo com HIV. Globalmente, a falta de ênfase nos direitos humanos e da participação comunitária tem como resultado políticas públicas de pior qualidade. Precisamos de uma nova agenda de pesquisa para responder a esses desafios.

El artículo ofrece una perspectiva crítica de la investigación en ciencias sociales, presentada en la Conferencia Internacional de SIDA en Melbourne (Australia), 2014. En tiempos de enormes avances biomédicos, la naturaleza política del VIH sigue siendo muy importante. Ninguna innovación será exitosa sin considerar el contexto sociopolítico y sus consecuencias. Cuatro temas surgieron de la conferencia en el campo legal y derechos humanos, además de investigación social y política: (1) la importancia del trabajo con grupos socialmente vulnerables, crecientemente denominados "poblaciones claves"; (2) el reconocimiento de que las acciones y programas deben ser adaptados a un contexto local; (3) la urgencia de una respuesta a una epidemia con crecimiento rápido entre adolescentes; (4) el efecto negativo de la creciente criminalización de las minorías sexuales y personas viviendo con VIH. Globalmente, un limitado énfasis en los derechos humanos y la participación comunitaria tiene como consecuencia peores políticas públicas. Necesitamos una nueva agenda de investigación para responder a estos desafíos.

Animals , Humans , Mice , Gene Silencing/physiology , Huntington Disease/therapy , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Blotting, Northern , Blotting, Western , Cell Line , Gene Expression Regulation/genetics , Huntington Disease/genetics , Huntington Disease/metabolism , Immunohistochemistry , MicroRNAs/genetics , MicroRNAs/physiology , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Oligonucleotide Array Sequence Analysis , Plasmids , Polymerase Chain Reaction , RNA, Small Interfering/genetics , RNA, Small Interfering/physiology
Rev. bras. cir. cardiovasc ; 30(1): 55-62, Jan-Mar/2015. tab
Article in English | LILACS | ID: lil-742887


Introduction: Complete denervation of transplanted heart exerts protective effect against postoperative atrial fibrillation; various degrees of autonomic denervation appear also after transection of ascending aorta during surgery for aortic aneurysm. Objective: This study aimed to evaluate if the level of cardiac denervation obtained by resection of ascending aorta could exert any effect on postoperative atrial fibrillation incidence. Methods: We retrospectively analysed the clinical records of 67 patients submitted to graft replacement of ascending aorta (group A) and 132 with aortic valve replacement (group B); all episodes of postoperative atrial fibrillation occurred during the 1-month follow-up have been reported. Heart Rate Variability parameters were obtained from a 24-h Holter recording; clinical, echocardiographic and treatment data were also evaluated. Results: Overall, 45% of patients (group A 43%, group B 46%) presented at least one episode of postoperative atrial fibrillation. Older age (but not gender, abnormal glucose tolerance, ejection fraction, left atrial diameter) was correlated with incidence of postoperative atrial fibrillation. Only among a subgroup of patients with aortic transection and signs of greater autonomic derangement (heart rate variability parameters below the median and mean heart rate over the 75th percentile), possibly indicating more profound autonomic denervation, a lower incidence of postoperative atrial fibrillation was observed (22% vs. 54%). Conclusion: Transection of ascending aorta for repair of an aortic aneurysm did not confer any significant protective effect from postoperative atrial fibrillation in comparison to patients with intact ascending aorta. It could be speculated that a limited and heterogeneous cardiac denervation was produced by the intervention, creating an eletrophysiological substrate for the high incidence of postoperative atrial fibrillation observed. .

Introdução: Denervação completa do coração transplantado exerce efeito protetor contra a fibrilação atrial no pós-operatório; vários graus de denervação autonômica aparecem também após a transecção da aorta ascendente durante a cirurgia de aneurisma da aorta. Objetivo: Este estudo teve como objetivo avaliar se o nível de denervação cardíaca obtida por ressecção da aorta ascendente poderia exercer algum efeito sobre a incidência de fibrilação atrial no pós-operatório. Métodos: Foram analisados retrospectivamente os prontuários de 67 pacientes submetidos a enxerto de substituição de aorta torácica (grupo A) e 132 com a substituição da valva aórtica (grupo B). Foram relatados todos os episódios de fibrilação atrial pós-operatória ocorridos durante 1 mês de seguimento. Parâmetros de variabilidade da frequência cardíaca foram obtidos a partir de 24 h de gravação do Holter; dados clínicos, ecocardiográficos e de tratamento também foram avaliados. Resultados: No geral, 45% dos pacientes (grupo A 43%, grupo B 46%) apresentaram pelo menos um episódio de fibrilação atrial no pós-operatório. Idade mais avançada (mas não gênero, tolerância à glicose anormal, fração de ejeção, diâmetro do átrio esquerdo) foi correlacionada com a incidência de fibrilação atrial pós-operatória. Apenas em um subgrupo de pacientes com transecção aórtica e sinais de maior desarranjo autonômico (parâmetros de variabilidade da frequência cardíaca abaixo da mediana e a média de frequência cardíaca acima do percentil 75), indicando possivelmente denervação autonômica mais profunda, foi observada menor incidência de fibrilação atrial pós-operatória (22% vs. 54%). Conclusão: Transecção da aorta ascendente para correção de um aneurisma da aorta não confere qualquer efeito protetor significativo de fibrilação atrial no pós-operatório em comparação com pacientes com aorta ascendente intacta. Pode-se especular que uma denervação cardíaca limitada e heterogênea foi produzida pela ...

Animals , Mice , Brain/physiology , Nerve Tissue Proteins/physiology , Poly Adenosine Diphosphate Ribose/antagonists & inhibitors , Stroke/physiopathology , Apoptosis Inducing Factor/physiology , Blotting, Northern , Calcium/metabolism , Cell Death/physiology , Glutamic Acid/drug effects , Glutamic Acid/physiology , Mitochondria/metabolism , Nerve Tissue Proteins/metabolism , Protein Binding , Poly(ADP-ribose) Polymerases/metabolism , Poly(ADP-ribose) Polymerases/physiology , Receptors, N-Methyl-D-Aspartate/drug effects
Medicina (B.Aires) ; 74(4): 321-325, ago. 2014. ilus
Article in Spanish | LILACS | ID: lil-734393


Al producirse una lesión de médula espinal (LME), un sinnúmero de proteínas inhibidoras de la regeneración axonal ocupan el sitio de lesión en forma secuencial. La primer proteína en llegar al mismo se conoce como semaforina 3A (Sema3A), siendo además una de las más potentes por su acción de inhibir la regeneración axonal. A nivel mecanístico la unión de esta proteína al complejo-receptor neuronal neuropilin-1 (NRP-1)/PlexinA4 evita que se produzca regeneración axonal. En este trabajo de revisión se discutirá la acción de galectin-1 (Gal-1), una proteína endógena de unión a glicanos, que selectivamente se une al complejo-receptor NRP-1/PlexinA4 de las neuronas lesionadas a través de un mecanismo dependiente de interacciones lectina-glicano, interrumpiendo la señalización generada por Sema3A y permitiendo de esta manera la regeneración axonal y recuperación locomotora luego de producirse la LME. Mientras ambas formas de Gal-1 (monomérica y dimérica) contribuyen a la inactivación de la microglia, solo la forma dimérica de Gal-1 es capaz de unirse al complejo-receptor NRP-1/PlexinA4 y promover regeneración axonal. Por lo tanto, Gal-1 dimérica produce recuperación de las lesiones espinales interfiriendo en la señalización de Sema3A a través de la unión al complejo-receptor NRP-1/PlexinA4, sugiriendo el uso de esta lectina en su forma dimérica para el tratamiento de pacientes con LME.

When spinal cord injury (SCI) occurs, a great number of inhibitors of axonal regeneration consecutively invade the injured site. The first protein to reach the lesion is known as semaphorin 3A (Sema3A), which serves as a powerful inhibitor of axonal regeneration. Mechanistically binding of Sem3A to the neuronal receptor complex neuropilin-1 (NRP-1) / PlexinA4 prevents axonal regeneration. In this special article we review the effects of galectin-1 (Gal-1), an endogenous glycan-binding protein, abundantly present at inflammation and injury sites. Notably, Gal1 adheres selectively to the NRP-1/PlexinA4 receptor complex in injured neurons through glycan-dependent mechanisms, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. While both the monomeric and dimeric forms of Gal-1 contribute to ’switch-off’ classically-activated microglia, only dimeric Gal-1 binds to the NRP-1/PlexinA4 receptor complex and promotes axonal regeneration. Thus, dimeric Gal-1 promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A adhering to the NRP-1/PlexinA4 complex, supporting the use of dimeric Gal-1 for the treatment of SCI patients.

Animals , Humans , Mice , Axons/physiology , Galectin 1/physiology , Nerve Regeneration/physiology , Spinal Cord Injuries/physiopathology , Microglia/metabolism , Nerve Tissue Proteins/metabolism , Neuropilin-1/metabolism , Receptors, Cell Surface/metabolism , /physiology
Rev. Esc. Enferm. USP ; 48(spe): 53-58, 08/2014.
Article in English | LILACS, BDENF | ID: lil-731286


Objective To understand the experiences and expectations of nurses in the treatment of women with chronic venous ulcers. Method Phenomenological research was based on Alfred Schütz, whose statements were obtained in January, 2012, through semi-structured interviews with seven nurses. Results The nurse reveals the difficulties presented by the woman in performing self-care, the perceived limitations in the treatment anchored in motivation, and the values and beliefs of women. It showed professional frustration because venous leg ulcer recurrence, lack of inputs, interdisciplinary work and training of nursing staff. There was an expected adherence to the treatment of women, and it emphasized the need for ongoing care, supported self-care and standard practices in treatment. Conclusion That treatment of chronic venous leg ulcers constitutes a challenge that requires collective investment, involving women, professionals, managers and health institutions. .

Objetivo Comprender las experiencias y expectativas de enfermeras en el tratamiento de mujeres con úlcera venosa crónica. Método Investigación fenomenológica fundamentada en Alfred Schutz, que buscó Se realizó entrevista semiestructurada con siete enfermeras, en enero del 2012. Resultados La enfermera revela dificultades presentadas por la mujer para realizar el autocuidado, percibe limitaciones en el tratamiento relacionadas con la desmotivación, los valores y las creencias de las mujeres. Refiere frustración profesional debido a la recidiva de la lesión, a la falta de insumos, al deficiente trabajo interdisciplinar y a la limitada capacitación del equipo de enfermeras. Espera la adhesión de la mujer al tratamiento y resalta la necesidad del cuidado continuo, del autocuidado apoyado y de estandarizar conductas de tratamiento. Conclusión El tratamiento de la úlcera venosa crónica es un desafío que requiere contribución colectiva, involucrando a las mujeres, a los profesionales, a los gestores y a las instituciones de salud. .

Objetivo Compreender as experiências e expectativas de enfermeiras no tratamento de mulheres com úlcera venosa crônica na Atenção Primária à Saúde. Método Pesquisa fundamentada na fenomenologia social de Alfred Schütz, com depoimentos obtidos em janeiro de 2012, por meio de entrevista semiestruturada com sete enfermeiras. Resultados As enfermeiras revelam dificuldades apresentadas pelas mulheres com úlcera venosa crônica para realizar o autocuidado, percebem limitações na terapêutica ancoradas na desmotivação e nos valores e crenças das mulheres. Referem frustração profissional em razão da recidiva da lesão, falta de insumos e tecnologia, de trabalho interdisciplinar e da capacitação da equipe de enfermagem. Esperam a adesão das mulheres ao tratamento e ressaltam a necessidade do cuidado contínuo, do autocuidado apoiado e da padronização de condutas no tratamento. Conclusão O tratamento da úlcera venosa crônica constitui-se em um desafio que requer investimento coletivo, envolvendo a mulher, os profissionais, os gestores e as instituições de saúde. .

Animals , Caenorhabditis elegans Proteins/isolation & purification , Caenorhabditis elegans/metabolism , Cell Membrane/metabolism , Ion Channels/isolation & purification , Ion Channels/metabolism , Nerve Tissue Proteins/isolation & purification , Nerve Tissue Proteins/metabolism , Nervous System/metabolism , Neurons, Afferent/metabolism , Sensation/genetics , Amino Acid Sequence/genetics , Base Sequence/genetics , Behavior, Animal/drug effects , Behavior, Animal/physiology , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/cytology , Capsaicin/pharmacology , Cell Compartmentation/genetics , Cell Membrane/drug effects , Cell Membrane/ultrastructure , Gene Expression Regulation/physiology , Ion Channels/genetics , Ion Channels/ultrastructure , Molecular Sequence Data , Mutation/genetics , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/ultrastructure , Nervous System/cytology , Nervous System/drug effects , Neurons, Afferent/cytology , Neurons, Afferent/drug effects , Pain/genetics , Pain/metabolism , Pain/physiopathology , Phylogeny , Receptors, Drug/drug effects , Receptors, Drug/metabolism , Receptors, Drug/ultrastructure , Sensation/drug effects , Signal Transduction/genetics , TRPV Cation Channels , Transient Receptor Potential Channels
Article in English | WPRIM | ID: wpr-56432


This study was performed to assess the neurotoxic effects of methylmercury, arsanilic acid and danofloxacin by quantification of neural-specific proteins in vitro. Quantitation of the protein markers during 14 days of differentiation indicated that the mouse ESCs were completely differentiated into neural cells by Day 8. The cells were treated with non-cytotoxic concentrations of three chemicals during differentiation. Low levels of exposure to methylmercury decreased the expression of GABAA-R and Nestin during the differentiating stage, and Nestin during the differentiated stage. In contrast, GFAP, Tuj1, and MAP2 expression was affected only by relatively high doses during both stages. Arsanilic acid affected the levels of GABA(A)-R and GFAP during the differentiated stage while the changes of Nestin and Tuj1 were greater during the differentiating stage. For the neural markers (except Nestin) expressed during both stages, danofloxacin affected protein levels at lower concentrations in the differentiated stage than the differentiating stage. Acetylcholinesterase activity was inhibited by relatively low concentrations of methylmercury and arsanilic acid during the differentiating stage while this activity was inhibited only by more than 40 microM of danofloxacin in the differentiated stage. Our results provide useful information about the different toxicities of chemicals and the impact on neural development.

Acetylcholinesterase/metabolism , Animals , Arsanilic Acid/toxicity , Cell Differentiation/drug effects , Embryonic Stem Cells/cytology , Environmental Pollutants/toxicity , Fluorescent Antibody Technique , Fluoroquinolones/toxicity , Gene Expression Regulation/drug effects , Methylmercury Compounds/toxicity , Mice , Nerve Tissue Proteins/metabolism , Neurons/cytology , Tetrazolium Salts/metabolism , Thiazoles/metabolism
Biocell ; 37(2): 29-36, ago. 2013. ilus
Article in English | LILACS | ID: lil-708030


The present paper shows by means of confocal laser scanning microscopy the immunoreactivity of rat cerebellar Lugaro cells for calbindin, synapsin-I, PSD-95, GluR1, CaMKII alpha, and N-cadherin. Lugaro cells were easily characterized by their location beneath Purkinje cells. Calbindin revealed immunoreactivity in the cell body, and the axonal and dendritic processes. Synapsin-I labelled the presynaptic endings on Lugaro cells. Synapsin-I and PSD-95 immunoreactivity demonstrated the localization of presynaptic and postsynaptic endings surrounding cell soma, corresponding to afferent extrinsic and intrinsic cerebellar fibers. GluR1 immunoreactivity of the soma and cell processes indicates that Lugaro cells have functional ionotropic glutamate receptors that regulate calcium levels. CaMKII alpha immunoreactivity of L ugaro cell soma and processes suggest its participation as a molecular switch for long-term information storage, and serving as a molecular basis of long-term synaptic memory. N-cadherin immunoreactivity was correlated with somato-somatic and somato-dendritic junctions between Lugaro cells and their synaptic connections.

Animals , Rats , Cerebellum/cytology , Immunohistochemistry , Interneurons/cytology , Microscopy, Confocal , Interneurons/metabolism , Nerve Tissue Proteins/metabolism
Article in English | WPRIM | ID: wpr-25344


Spinal cord injury (SCI) causes not only loss of sensory and motor function below the level of injury but also chronic pain, which is difficult and challenging of the treatment. Repetitive transcranial magnetic stimulation (rTMS) to the motor cortex, of non-invasive therapeutic methods, has the motor and sensory consequences and modulates pain in SCI-patients. In the present study, we studied the effectiveness of rTMS and the relationship between the modulation of pain and the changes of neuroglial expression in the spinal cord using a rat SCI-induced pain model. Elevated expressions of Iba1 and GFAP, specific microglial and astrocyte markers, was respectively observed in dorsal and ventral horns at the L4 and L5 levels in SCI rats. But in SCI rats treated with 25 Hz rTMS for 8 weeks, these expressions were significantly reduced by about 30%. Our finding suggests that this attenuation of activation by rTMS is related to pain modulation after SCI. Therefore, rTMS might provide an alternative means of attenuating neuropathic pain below the level of SCI.

Animals , Astrocytes/cytology , Calcium-Binding Proteins/metabolism , Disease Models, Animal , Immunohistochemistry , Male , Microfilament Proteins/metabolism , Microglia/cytology , Nerve Tissue Proteins/metabolism , Neuralgia/etiology , Rats , Rats, Sprague-Dawley , Spinal Cord Injuries/complications , Transcranial Magnetic Stimulation
Article in English | WPRIM | ID: wpr-25343


Glial cells play a critical role in morphine tolerance, resulting from repeated administration of morphine. Both the development and the expression of tolerance are suppressed by the analgesic lamotrigine. This study investigated the relationship between the ability of lamotrigine to maintain the antinociceptive effect of morphine during tolerance development and glial cell activation in the spinal cord. In a rat model, morphine (15 microg) was intrathecally injected once daily for 7 days to induce morphine tolerance. Lamotrigine (200 microg) was co-administered with morphine either for 7 days or the first or last 3 days of this 7 day period. Thermal nociception was measured. OX-42 and GFAP immunoreactivity, indicating spinal microglial and astrocytic activation were evaluated on day 8. Tolerance developed after 7 days of intrathecal morphine administration; however, this was completely blocked and reversed by co-administration of lamotrigine. When lamotrigine was coinjected with morphine on days 5-7, the morphine effect was partially restored. Glial cell activation increased with the development of morphine tolerance but was clearly inhibited in the presence of lamotrigine. These results suggest that, in association with the suppression of spinal glial cell activity, intrathecally coadministered lamotrigine attenuates antinociceptive tolerance to morphine.

Analgesics/pharmacology , Animals , CD11b Antigen/metabolism , Astrocytes/cytology , Drug Tolerance , Immunohistochemistry , Male , Microglia/cytology , Morphine/pharmacology , Nerve Tissue Proteins/metabolism , Neuroglia/cytology , Rats , Rats, Sprague-Dawley , Spinal Cord/cytology , Triazines/pharmacology
Braz. j. med. biol. res ; 42(10): 935-941, Oct. 2009. ilus, tab
Article in English | LILACS | ID: lil-526197


A low-protein diet leads to functional and structural pancreatic islet alterations, including islet hypotrophy. Insulin-signaling pathways are involved in several adaptive responses by pancreatic islets. We determined the levels of some insulin-signaling proteins related to pancreatic islet function and growth in malnourished rats. Adult male Wistar rats (N = 20 per group) were fed a 17 percent protein (normal-protein diet; NP) or 6 percent protein (low-protein diet; LP), for 8 weeks. At the end of this period, blood glucose and serum insulin and albumin levels were measured. The morphometric parameters of the endocrine pancreas and the content of some proteins in islet lysates were determined. The β-cell mass was significantly reduced (≅65 percent) in normoglycemic but hypoinsulinemic LP rats compared to NP rats. Associated with these alterations, a significant 30 percent reduction in insulin receptor substrate-1 and a 70 percent increase in insulin receptor substrate-2 protein content were observed in LP islets compared to NP islets. The phosphorylated serine-threonine protein kinase (pAkt)/Akt protein ratio was similar in LP and NP islets. The phosphorylated forkhead-O1 (pFoxO1)/FoxO1 protein ratio was decreased by 43 percent in LP islets compared to NP islets (P < 0.05). Finally, the ratio of phosphorylated-extracellular signal-related kinase 1/2 (pErk1/2) to total Erk1/2 protein levels was decreased by 71 percent in LP islets compared to NP islets (P < 0.05). Therefore, the reduced β-cell mass observed in LP rats is associated with the reduction of phosphorylation in mitogenic-related signals, FoxO1 and Erk proteins. The cause/effect basis of this association remains to be determined.

Animals , Male , Rats , Forkhead Transcription Factors/metabolism , Insulin-Secreting Cells/pathology , /metabolism , Nerve Tissue Proteins/metabolism , Protein-Energy Malnutrition , Diet, Protein-Restricted , Phosphorylation , Protein-Energy Malnutrition/metabolism , Protein-Energy Malnutrition/pathology , Rats, Wistar
Arq. neuropsiquiatr ; 67(3a): 684-688, Sept. 2009. ilus
Article in English | LILACS | ID: lil-523620


OBJECTIVE: Nestin is temporarily expressed in several tissues during development and it is replaced by other protein types during cell differentiation process. This unique property allows distinguishing between undifferentiated and differentiated cells. This study was delineated to analyze the temporal pattern of nestin expression in cortical radial glial cells of rats during normal development and of rats submitted to recurrent status epilepticus (SE) in early postnatal life (P). METHOD: Experimental rats were submitted to pilocarpine-induced SE on P7-9. The cortical temporal profile of nestin was studied by immunohistochemistry at multiple time points (P9, P10, P12, P16, P30 and P90). RESULTS: We observed delayed nestin down-regulation in experimental rats of P9, P10, P12 and P16 groups. In addition, few radial glial cells were still present only in P21 experimental rats. CONCLUSION: Our results suggested that SE during early postnatal life alters normal maturation during a critical period of brain development.

OBJETIVO: A nestina, temporariamente expressa em diversos tecidos durante o desenvolvimento, é substituída no processo de diferenciação celular, o que permite a distinção entre células diferenciadas e indiferenciadas. O objetivo deste estudo foi verificar o padrão temporal da expressão da nestina nas células da glia radial cortical de ratos durante o desenvolvimento normal e nos ratos submetidos a sucessivos status epilepticus (SE) no periodo pós-natal precoce (P). MÉTODO: Os animais foram submetidos ao SE induzido pela pilocarpina em P7-9. O perfil temporal da nestina foi estudado por imuno-histoquímica em P9, P10, P12, P16, P30 e P90. RESULTADOS: Nos ratos experimentais, observamos atraso no desaparecimento da nestina nos grupos P9, P10, P12 e P16. Ainda, encontramos algumas glias radiais corticais apenas em P21 experimental. CONCLUSÃO: Nossos resultados sugerem que o SE durante o desenvolvimento pós-natal precoce altera o processo de maturação durante um periodo crítico do desenvolvimento encefálico.

Animals , Rats , Cerebral Cortex/cytology , Intermediate Filament Proteins/metabolism , Nerve Tissue Proteins/metabolism , Neuroglia/metabolism , Status Epilepticus/metabolism , Animals, Newborn , Biomarkers/metabolism , Disease Models, Animal , Immunohistochemistry , Intermediate Filament Proteins/analysis , Nerve Tissue Proteins/analysis , Neuroglia/cytology , Pilocarpine/administration & dosage , Rats, Wistar , Status Epilepticus/chemically induced
Article in English | IMSEAR | ID: sea-23936


BACKGROUND & OBJECTIVES: Rising prevalence of neurodegenerative disorders with a steady increase in aged-population necessitates studies of the human brain to understand their pathophysiology. As animal models are not available, medical centers have established "brain banks" to provide autopsy brain samples for such research. Frozen tissues must be of optimal quality to permit molecular and protein studies. Post-mortem interval (PMI) is an important factor affecting tissue quality although its effects on brain physiology are unclear. We undertook this study to analyze the biochemical effects of PMI on protein stability in human brains collected at autopsy and stored at the brain bank of a tertiary care neurosciences institute in south India. METHODS: Different neuroanatomical areas including frontal cortex (FC), cerebellum (CB), caudate nucleus (CD) and substantia nigra (SN) from autopsy human brains (n=9) with varying PMI (4-18 h) were analyzed for pH, protein insolubility, protein oxidation/ nitration and protein expression of glial fibrillary acidic protein (GFAP), synatophysin and neurofilament (NF). Histological changes at different PMI were also assessed. RESULTS: An increase in tissue pH was noted with increasing PMI. Although there was no significant alteration in solubility of proteins, SN showed increased protein oxidation/nitration events, GFAP and NF expression with increasing PMI. No major abnormalities in cell morphology or tissue integrity were noted. Immunohistochemistry with GFAP and NF did not show any significant increase in signal in FC at high PMI. INTERPRETATION & CONCLUSION: In post-mortem human brains, although there were no gross structural changes at the tissue level with increasing PMI, biochemical events such as oxidative and nitrosative damage of cellular proteins, tissue pH could be considered as markers of tissue quality for biochemical research. Further, SN was found to be most susceptible to PMI related changes.

Adult , Analysis of Variance , Blotting, Western , Brain/metabolism , Electrophoresis, Polyacrylamide Gel , Humans , Hydrogen-Ion Concentration , Immunohistochemistry , India , Nerve Tissue Proteins/metabolism , Postmortem Changes , Protein Stability , Time Factors
Arq. neuropsiquiatr ; 66(2b): 385-390, jun. 2008. graf, tab
Article in English | LILACS | ID: lil-486196


Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5 percent), >20 percent of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40 percent) and 8 (20 percent) cases, respectively. P53 was positive in 18 (45 percent) cases, with 11 (61 percent) weakly positive and 7 (39 percent) strongly positive. HER2 was positive in 23 (57.5 percent) of the samples and did not show statistical association with survival (p=0.07).

Meduloblastoma (MB) é o tumor maligno encefálico mais freqüente na infância. dentre as alterações encontradas estão: a presença das oncoproteínas p53 e HER2, elevado índice mitótico e presença de diferenciação neuronal. o objetivo deste estudo foi determinar a expressão imunoistoquímica (IMQ) dos marcadores Ki-67, NeuN, sinaptofisina, HER2 e p53 em 40 amostras de MB, correlacionando-as com parâmetros clinicopatológicos e com a sobrevida. Vinte e nove pacientes (72,5 por cento) apresentaram 20 por cento ou mais das células positivas para Ki-67. os pacientes do sexo masculino apresentaram maior expressão do Ki-67 (p=0,02) e também menor sobrevida (p=0,002). NeuN e sinaptofisina foram negativos em 16 (40 por cento) e 8 (20 por cento) casos, respectivamente. P53 foi positivo em 18 (45 por cento) casos, sendo 11 (61 por cento) fracamente positivos e 7 (39 por cento) fortemente positivos. HER2 foi positivo em 23 (57,5 por cento) das amostras e não demonstrou associação estatística com a sobrevida (p=0.07).

Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Cerebellar Neoplasms/pathology , Medulloblastoma/pathology , Biomarkers, Tumor/metabolism , Antigens, Nuclear/metabolism , Brazil/epidemiology , Cerebellar Neoplasms/metabolism , Cerebellar Neoplasms/mortality , Epidemiologic Methods , /metabolism , Medulloblastoma/metabolism , Medulloblastoma/mortality , Neoplasm, Residual , Nerve Tissue Proteins/metabolism , /metabolism , Synaptophysin/metabolism , /metabolism