219 research outputs found
Clonagem e células-tronco
ALTHOUGH concepts such as human cloning (reproductive and therapeutic), stem cells (embryonic and non-embryonic) , and stem cell therapy and how these issues may affect our lives have been extensively discussed, there is still a lot of misunders-tanding. Therefore the aim of this article is to try to better explain these definitions and express my personal opinion on ethical aspects not only as a scientist but also as a representative of inumerous families who hope that this technology might represent in the future a treatment for many neurodegenerative disorders often lethal or severely disabling.APESAR do muito que se tem discutido, ainda existe muita confusão em relação aos conceitos de clonagem (reprodutiva e terapêutica) , células-tronco ( embrionárias e não embrionárias) e terapia celular bem como isso pode afetar as nossas vidas. Portanto a proposta desse artigo é o de tentar definir esses conceitos e expressar a minha posição sobre aspectos éticos não só como cientista mas também como representante de inúmeras famílias que vêem nessa nova tecnologia uma esperança futura de cura para inúmeras doenças neurodegenerativas , muitas vezes letais ou gravemente incapacitantes
Correlação entre o tempo de realização de diferentes atividades físicas por portadores de distrofia muscular de Duchenne
DMD is a disease determined by genetic disturbance of recessive character linked to the chromosome X, that determines the deficiency or absence in the distrofin production in the muscular cellular membrane, carting a progressive and irreversible dysfunction, mainly of the skeletal musculature. The functional evaluation of the children carriers of DMD is extensive and exhaustive for child and for physical therapist. The search of information and methods that promote the facilitation or simplification of the routines of functional evaluation has been conducting to the research of correlations among the time of development of functional activities. The goal of this study was to determine and to research possible correlations among the time used to realize physical activities (to go up stairway, to go down stairway, to lift of the chair and to pass from sitting on the floor to standing through the Maneuver of Gowers) in 15 children (6 to 10 years old) with DMD. The children were filmed accomplishing the proposed physical activities, in five serial evaluations during one year, separated by a period of three months. The time for each activity was measured for each child. We confirmed the heterogeneity of the evolution of the disease, in the studied activities, as expected. We found lineal relationship among the functional activities and the age, and the presence of direct lineal correlation between the accomplishment of the Maneuver of Gowers and the functional activities. Up stairway was the activity of larger correlation.A DMD é uma doença determinada por um distúrbio genético de caráter recessivo ligada ao cromossomo X, que determina a deficiência ou ausência na produção de distrofina na membrana celular muscular, acarretando uma disfunção progressiva e irreversível, principalmente da musculatura esquelética. A avaliação funcional das crianças portadoras de DMD é extensa e exaustiva, tanto para criança, quanto para o fisioterapeuta. A procura de informações e métodos que promovam a facilitação ou simplificação das rotinas de avaliação fisioterápica tem conduzido à pesquisa de correlações entre o tempo de desenvolvimento de atividades funcionais. O objetivo desse estudo foi determinar e pesquisar possíveis correlações entre o tempo utilizado na realização de diferentes atividades físicas, a saber, subir escada, descer escada, levantar da cadeira e passar da postura de sedestação no solo para bipedestação (através da Manobra de Gowers) em 15 crianças (de 6 a 10 anos) portadoras de Distrofia Muscular de Duchenne. As crianças foram filmadas realizando as atividades físicas propostas, em cinco avaliações consecutivas durante um ano, separadas por um período de três meses. Posteriormente cronometrou-se o tempo para realização das atividades. Confirmou-se a heterogeneidade da evolução da doença, para as atividades estudadas, como esperado. Encontrou-se relação linear entre as atividades funcionais estudadas e a idade, e a presença de correlação linear direta entre a realização da Manobra de Gowers e as atividades funcionais, sendo o subir escada a atividade de maior correlação
Efeito da fisioterapia na amplitude de movimento articular e deposição de colágeno muscular no modelo golden retriever muscular dystrophy (GRMD)
OBJETIVO: Elucidar o efeito da fisioterapia na Amplitude de Movimento Articular (ADM) e na fibrose muscular em animais GRMD. MÉTODOS: Estudo não randomizado, com grupo controle, cego, seis meses de intervenção, avaliação antes e depois da intervenção. Seis animais da raça Golden Retriever, distróficos, machos, média de idade 10,16±3,46 meses e peso de 17,75±6,01 kg foram separados em grupo tratado (n=3) e não tratado. Esses grupos de animais foram nomeados: G1=grupo tratado antes do tratamento; G2=grupo tratado após tratamento; G3=grupo não tratado antes do tratamento; G4=grupo não tratado após tratamento. O G1 participou do programa de fisioterapia que consistiu em um circuito de 300 metros com obstáculos. As ADMs do joelho, tarso, cotovelo e carpo foram avaliadas com goniômetro antes e após o tratamento. A área de colágeno do músculo vastus lateralis foi mensurada por histomorfometria, e a localização dos tipos de colágeno I, III e IV foi estudada por Imuno-histoquímica (IHC). RESULTADOS: Os valores da ADM do tarso do G2 apresentaram uma tendência a aumentar. A área de colágeno muscular foi diferente entre os grupos após o tratamento, e uma tendência ao aumento desses valores no G4 foi observada. Os colágenos dos tipos I e III foram os mais observados, constituindo feixes largos no perimísio nos dois grupos (G2 e G4). O colágeno do tipo I foi mais observado no endomísio do que o colágeno do tipo III. O colágeno do tipo IV foi observado apenas na lâmina basal. CONCLUSÃO: A Fisioterapia parece aumentar a ADM do tarso dos animais do grupo tratado sem aumentar a fibrose muscularOBJECTIVE: To elucidate the effect of physical therapy on joint range of motion (ROM) and muscle fibrosis in GRMD animals.METHODS: This was a nonrandomized blinded study with a control group, with six months of intervention evaluated beforehand and afterwards. Six dystrophic male Golden Retrievers of mean age 10.16±3.46 months and weight 17.75±6.01 kg were divided into a treated group (n=3) and an untreated group. These groups of dogs were named: G1=treated group before treatment; G2=treated group after treatment; G3=untreated group before treatment; and G4=untreated group after treatment. G1 underwent a physical therapy program that consisted of a 300-meter circuit with obstacles. Stifle, tarsal, elbow and carpal ROM were assessed using a goniometer before and after treatment. The area of collagen in the vastus lateralis muscle was measured using histomorphometry. The locations of collagen types I, III and IV were studied usingmmunohistochemistry. RESULTS: The tarsal ROM values in G2 presented an increasing trend. The area of muscle collagen differed between the groups after treatment and an increasing trend in these values was observed in G4. Collagen types I and III were the ones most frequently observed, forming broad bands in the perimysium of both G2 and G4. Type I collagen was observed in the endomysium more than type III collagen. Type IV collagen was observed only in the basal layer. CONCLUSION: Physical Therapy seemed to improve tarsal ROM in the treated group without increasing muscular fibrosi
Caracterização da passagem da postura de bipedestação para a de sedestação no solo, em crianças portadoras de Distrofia Muscular de Duchenne
Duchenne Muscular Dystrophy (DMD) is a genetically determinated pathology, X-linked recessive A DMD child presents irreversible and progressive muscle weakness, causing difficulties in funcional activities. The objective of this study was described the transference of posture from orthostatism to sitting on the floor in 43 children with DMD, from five to ten years of age (average age of 7,4 years). They were filmed and we observed the transference of posture by videotape and the datas was correlated with the child's age and the time expended in the posture tranference. It was found two characteristic forms to realize this maneuver with five variations to each one. It was notted relationship between the child's age and the form adopted to realize the transference, but it wasn't noted any relation with the the time expended in the posture transference.A Distrofia Muscular de Duchenne (DMD) é uma patologia geneticamente determinada, recessiva, ligada ao cromossomo X. A criança portadora de DMD apresenta fraqueza progressiva e irreversível da musculatura esquelética, prejudicando a realização de atividades motoras. O objetivo deste estudo foi descrever a mudança de postura de bipedestação para sedestação no solo, em 43 crianças com idades entre cinco e dez anos (média de 7,4 anos), portadoras de DMD. As crianças foram filmadas realizando as mudanças de decúbito e posteriormente estudou-se a transferência de postura através da observação dos filmes, evitando assim, a repetição desnecessária das manobras pelas crianças. Correlacionou-se os achados sobre o desempenho nesta tarefa com a idade e o tempo utilizado para a mudança de postura. Posteriormente caracterizou-se os movimentos utilizados na passagem da postura de bipedestação para sedestação. Encontrou-se duas formas características de realização desta manobra, com cinco variações cada. Observou-se relação entre a idade da criança e a forma adotada para realizar a mudança de postura, não havendo relação com o tempo de realização
A rigorous approach to facilitate and guarantee the correctness of the genetic testing management in human genome information systems
<p>Abstract</p> <p>Background</p> <p>Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes.</p> <p>Results</p> <p>This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra.</p> <p>Conclusions</p> <p>This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces.</p
Avaliação motora e funcional de pacientes com paraplegia espástica, atrofia óptica e neuropatia (SPOAN)
Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive complicated form of hereditary spastic paraplegia, which is clinically defined by congenital optic atrophy, infancy-onset progressive spastic paraplegia and peripheral neuropathy. In this study, which included 61 individuals (age 5-72 years, 42 females) affected by SPOAN, a comprehensive motor and functional evaluation was performed, using modified Barthel index, modified Ashworth scale, hand grip strength measured with a hydraulic dynamometer and two hereditary spastic paraplegia scales. Modified Barthel index, which evaluate several functional aspects, was more sensitive to disclose disease progression than the spastic paraplegia scales. Spasticity showed a bimodal distribution, with both grades 1 (minimum) and 4 (maximum). Hand grip strength showed a moderate inverse correlation with age. Combination of early onset spastic paraplegia and progressive polyneuropathy make SPOAN disability overwhelming.A paraplegia espástica, atrofia óptica e neuropatia (SPOAN) é uma forma complicada de paraplegia espástica de herança autossômica recessiva, caracterizada por atrofia óptica congênita, paraplegia espástica progressiva de início na infância e neuropatia periférica. Este estudo avaliou o desempenho motor e funcional de 61 indivíduos com SPOAN (5 a 72 anos), por meio do índice de Barthel modificado, a escala modificada de Ashworth, da avaliação da força de preensão das mãos com dinamômetro hidráulico de Jamar e escalas de paraplegia espástica hereditária. O índice de Barthel modificado, que investiga aspectos funcionais, mostrou-se mais sensível para avaliar a progressão da doença do que as escalas de paraplegia espástica. A espasticidade apresentou distribuição bimodal, com o grau 1 (mínimo) e 4 (máximo). A força de preensão mostrou correlação inversa moderada com a idade. A combinação de paraplegia espástica de início precoce com polineuropatia progressiva faz da SPOAN uma condição incapacitante
Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy
Umbilical cord mesenchymal stromal cells (MSC) have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs), independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cells in vivo in two animal models of PMDs. In order to address this question we injected (1) human umbilical cord tissue (hUCT) MSCs into the caudal vein of SJL mice; (2) hUCT and canine umbilical cord vein (cUCV) MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies
Human fallopian tube: a new source of multipotent adult mesenchymal stem cells discarded in surgical procedures
<p>Abstract</p> <p>Background</p> <p>The possibility of using stem cells for regenerative medicine has opened a new field of investigation. The search for sources to obtain multipotent stem cells from discarded tissues or through non-invasive procedures is of great interest. It has been shown that mesenchymal stem cells (MSCs) obtained from umbilical cords, dental pulp and adipose tissue, which are all biological discards, are able to differentiate into muscle, fat, bone and cartilage cell lineages. The aim of this study was to isolate, expand, characterize and assess the differentiation potential of MSCs from human fallopian tubes (hFTs).</p> <p>Methods</p> <p>Lineages of hFTs were expanded, had their karyotype analyzed, were characterized by flow cytometry and underwent <it>in vitro </it>adipogenic, chondrogenic, osteogenic, and myogenic differentiation.</p> <p>Results</p> <p>Here we show for the first time that hFTs, which are discarded after some gynecological procedures, are a rich additional source of MSCs, which we designated as <it>human tube MSCs </it>(htMSCs).</p> <p>Conclusion</p> <p>Human tube MSCs can be easily isolated, expanded <it>in vitro</it>, present a mesenchymal profile and are able to differentiate into muscle, fat, cartilage and bone <it>in vitro</it>.</p
Gene Expression Profile of Mesenchymal Stem Cells from Paired Umbilical Cord Units: Cord is Different from Blood
Mesenchymal stem cells (MSC) are multipotent cells which can be obtained from several adult and fetal tissues including human umbilical cord units. We have recently shown that umbilical cord tissue (UC) is richer in MSC than umbilical cord blood (UCB) but their origin and characteristics in blood as compared to the cord remains unknown. Here we compared, for the first time, the exonic protein-coding and intronic noncoding RNA (ncRNA) expression profiles of MSC from match-paired UC and UCB samples, harvested from the same donors, processed simultaneously and under the same culture conditions. The patterns of intronic ncRNA expression in MSC from UC and UCB paired units were highly similar, indicative of their common donor origin. The respective exonic protein-coding transcript expression profiles, however, were significantly different. Hierarchical clustering based on protein-coding expression similarities grouped MSC according to their tissue location rather than original donor. Genes related to systems development, osteogenesis and immune system were expressed at higher levels in UCB, whereas genes related to cell adhesion, morphogenesis, secretion, angiogenesis and neurogenesis were more expressed in UC cells. These molecular differences verified in tissue-specific MSC gene expression may reflect functional activities influenced by distinct niches and should be considered when developing clinical protocols involving MSC from different sources. In addition, these findings reinforce our previous suggestion on the importance of banking the whole umbilical cord unit for research or future therapeutic use
IFNγ protects motor neurons from oxidative stress via enhanced global protein synthesis in FUS-associated amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis type 6 (ALS6) is a familial subtype of ALS linked to Fused in Sarcoma (FUS) gene mutation. FUS mutations lead to decreased global protein synthesis, but the mechanism that drives this has not been established. Here, we used ALS6 patient-derived induced pluripotent stem cells (hIPSCs) to study the effect of the ALS6 FUSR521H mutation on the translation machinery in motor neurons (MNs). We find, in agreement with findings of others, that protein synthesis is decreased in FUSR521H MNs. Furthermore, FUSR521H MNs are more sensitive to oxidative stress and display reduced expression of TGF-β and mTORC gene pathways when stressed. Finally, we show that IFNγ treatment reduces apoptosis of FUSR521H MNs exposed to oxidative stress and partially restores the translation rates in FUSR521H MNs. Overall, these findings suggest that a functional IFNγ response is important for FUS-mediated protein synthesis, possibly by FUS nuclear translocation in ALS6.</p
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