Regeneration of adult skeletal muscle relies upon a population of quiescent myogenic progenitor cells, called satellite cells (SCs). Upon injury, SCs activate, proliferate, differentiate and fuse to make new myofibers or to repair damaged ones. SCs can also self-renew to repopulate the SC niche. The balance between differentiation and self-renewal is critical to maintain muscle homeostasis and changes in this equilibrium can lead to chronic muscle degeneration. For example, Duchenne’s muscular dystrophy (DMD) is characterized by rounds of muscle degeneration and regeneration leading to increased muscle wasting. One approach to treat DMD is transplantation of SCs. For this treatment to be viable, transplanted cells must contribute to repairing injured muscle and repopulating the SC niche. Here, we show that the transcription factor CCAAT/Enhancer Binding Protein beta (C/EBPβ) regulates SC function. C/EBPβ is down-regulated during differentiation and persistent expression of C/EBPβ inhibits differentiation and expression of the myogenic regulatory factors MyoD and Myogenin. C/EBPβ also promotes Pax7 expression by directly binding to and regulating Pax7 transcription. Using genetic tools to conditionally excise C/EBPβ expression in SCs, we found that C/EBPβ-null SCs lose quiescence and precociously differentiate at the expense of self-renewal. After a single injury, C/EBPβ-deficient SCs failed to self-renew, resulting in impaired muscle repair after a second injury. C/EBPβ-induced quiescence also requires upregulation of caveolin-1. Furthermore, pharmacological manipulation of C/EBPβ expression with the phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX), increased the number of cells available for transplantation into dystrophic muscle and enhanced the expression of stem cell markers in a C/EBPβ-dependent fashion. IBMX treatment improved cell survival and migration, engraftment into the SC niche and repair of dystrophic muscle. Together, these results demonstrate that C/EBPβ is an important regulator of SC function and that pharmacological manipulation of C/EBPβ improves culture conditions for the expansion and selection of SCs available for cell therapy for the treatment of muscular dystrophies.

Rationale and Aims: Research into the lived experience of parenting children with muscular dystrophy has typically addressed key transitions along the disease trajectory, such as diagnosis or end-of-life care. Families reportedly face continuous challenges as their child's health deteriorates. No research has considered accounts of parenting across the lifespan that look at adaptation following their child's death. This research was conducted in the context of a wish-fulfilment charity that offer experiences for children to be supported in activities that are usually deemed inaccessible. In this context, the study asked how do parents who have lost a child to muscular dystrophy story their experiences of parenting. Methods: This research used a qualitative approach that explored the accounts of eight parents interviewed in couples, all of who had experienced the death of their child to muscular dystrophy. The study used a semi-structured interview, lasting from 100-150 minutes each. Interviews were video-recorded, transcribed, and analysed using narrative analysis to explore what and how the parents narrated their experiences. Consideration was given to the social and cultural contexts that shaped these. Analysis: Multiple readings of the transcripts allowed me to develop individual summaries and then construct an analysis across all of the accounts. Three main stories of change, survival and creating change emerged through my analysis. These three stories represented six sub-stories in total: waking up to different futures; being so close, you don't see the deterioration; humour through the struggle; storytelling together; creating a legacy; and living the dream. Findings: Couples narrated the loss of parental dreams, leading to the need for identity (re)formation. Humour and storytelling together were often used to regulate emotions during the storying telling, and a means of surviving their loss. Parents shared narratives of building legacies and the memories created through 'living the dream', which alluded to an impact that surpassed death itself. Implications: These findings suggest the need for greater consideration of sense-making, changing identities, and benefit-finding in clinical consultations, at key transitions during the parenting journey and particularly following the death of a child to muscular dystrophy. Accounts suggest that wish-fulfilment events can sustain hope for parents, a proposition that will need further investigation in the future.

xiv, 78 p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / Myotonic Dystrophy (DM) is a genetic disorder with multisystemic symptoms that is caused by expression (as RNA) of expanded repeats of CTG or CCTG in the genome. It is hypothesized that the protein MBNL1 (M[barbelow]uscleb[barbelow]lin[barbelow]d-l[barbelow]ike-1) is sequestered to the expanded CUG or CCUG RNAs. MBNL1 regulates the alternative splicing of a variety of pre-mRNAs and its mis-localization results in mis-splicing of a subset of pre-mRNAs that are linked to the symptoms found in DM patients. I initially demonstrated that MBNL1 can bind short structured CUG and CCUG repeats with high affinity and specificity in vitro . Next, I was able to determine and articulate the first structure of a binding site of MBNL1 in an endogenous pre-mRNA that it regulates. I found that MBNL1 binds a stem-loop in the cardiac troponin T (cTNT) pre-mRNA. The stem-loop contains two mismatches and resembles both CUG and CCUG repeats. I determined that MBNL1 regulated exon 5 by directly competing with the essential splicing factor U2AF65 for binding upstream of exon 5. When U2AF65 is prevented from binding, factors in the spliceosome can no longer be recruited and the following exon is skipped. Furthermore, I found that MBNL1 and U2AF65 compete by binding mutually exclusive RNA structures. I also characterized a potential therapeutic approach for DM. Current data suggest that if MBNL1 is released from sequestration, disease symptoms may be alleviated. Using a targeted screen of small molecules known to bind structured nucleic acids, I identified the small molecule pentamidine as a compound that disrupted MBNL1 binding to CUG repeats in vitro . I showed in cell culture that pentamidine was able to reverse the mis-splicing of two pre-mRNAs affected in DM. Pentamidine also significantly reduced the formation of RNA foci in tissue culture cells, which are characteristic of DM. MBNL1 was released from the foci in the treated cells. Furthermore, pentamidine partially rescued splicing defects of two pre-mRNAs in mice expressing expanded CUG repeats. This dissertation includes three previously published co-authored publications. / Committee in charge: Kenneth Prehoda, Chairperson, Chemistry; J. Andrew Berglund, Advisor, Chemistry; Victoria DeRose, Member, Chemistry; Peter von Hippel, Member, Chemistry; Alice Barkan, Outside Member, Biology

Made available in DSpace on 2015-07-22T20:49:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-22. Added 1 bitstream(s) on 2015-08-11T03:26:04Z : No. of bitstreams: 1 Publico-12588a.pdf: 1268307 bytes, checksum: cbc2db02b2ce425ce0a255bc9cbeef4c (MD5). Added 1 bitstream(s) on 2015-08-11T03:26:05Z : No. of bitstreams: 2 Publico-12588a.pdf: 1268307 bytes, checksum: cbc2db02b2ce425ce0a255bc9cbeef4c (MD5) Publico-12588b.pdf: 1611234 bytes, checksum: 5bb4cedebc746bef2f551f891a283a74 (MD5) / Fundamento: É conhecido o envolvimento cardíaco em pacientes com distrofia muscular de Duchenne (DMD). O eletrocardiograma (ECG) apresenta algumas alterações típicas na DMD, fato que o torna um exame útil no diagnóstico da lesão cardíaca nessa patologia. Objetivo: Avaliar as alterações eletrocardiográficas em pacientes portadores de DMD, correlacionando-as com a idade da população estudada. Métodos: Foram analisados os ECG de 131 pacientes com diagnóstico do DMD. Avaliaram-se diversas variáveis eletrocardiográficas, sendo os pacientes separados em dois grupos: aqueles com e sem alterações, por variável estudada. Fezse a correlação desses dois grupos com a idade dos pacientes. Foram utilizados os critérios de Garson para estabelecer os parâmetros eletrocardiográficos de normalidade. Resultados: O ECG estava anormal em 78,6% dos pacientes. Todos apresentavam ritmo sinusal. Foram os seguintes os percentuais encontrados para as principais variáveis estudadas: PR curto= 18,3%, ondas R anormais em V1 = 29,7%, onda Q anormais em V6 = 21,3%, alterações da repolarização ventricular = 54,9%, ondas QS anormais em paredes inferior e/ou lateral alta = 37,4%, distúrbios de condução pelo ramo direito = 55,7%, intervalo QTc prolongado = 35,8% e alargamento do QRS = 23,6%. O teste t, não pareado, foi utilizado para se estabelecer a correlação da idade com as variáveis eletrocardiográficas estudadas nos dois grupos e, apenas a variável alteração da repolarização mostrou diferença estatisticamente significante. Conclusão: As alterações eletrocardiográficas na DMD são frequentes, revelando comprometimento cardíaco precoce. Apenas a variável alteração da repolarização ventricular foi mais frequente, porém em faixa etária menor (p<0,05). / TEDE / BV UNIFESP: Teses e dissertações

FEITOSA FILHO, Odimar Araújo. Vigorexia: Uma Leitura Psicanalítica. 2008. 150f. – Dissertação (Mestrado) – Universidade Federal do Ceará, Programa de Pós-graduação em Psicologia, Fortaleza (CE), 2008. / Submitted by Márcia Araújo (marcia_m_bezerra@yahoo.com.br) on 2013-11-22T14:04:47Z No. of bitstreams: 1 2008-DIS-OAFFILHO.pdf: 921570 bytes, checksum: ae427896bedb37ae0f93107e2296d26b (MD5) / Approved for entry into archive by Márcia Araújo(marcia_m_bezerra@yahoo.com.br) on 2013-11-22T16:20:07Z (GMT) No. of bitstreams: 1 2008-DIS-OAFFILHO.pdf: 921570 bytes, checksum: ae427896bedb37ae0f93107e2296d26b (MD5) / Made available in DSpace on 2013-11-22T16:20:07Z (GMT). No. of bitstreams: 1 2008-DIS-OAFFILHO.pdf: 921570 bytes, checksum: ae427896bedb37ae0f93107e2296d26b (MD5) Previous issue date: 2008 / This study concerns to muscular dystrophy, also knows overtraining. The research considers that overtraining is not a psychoanalytic concept, but that it is possible to make both approches closer through freudo-lacanian psychoanalysis. So, this work aims at analyzing, from psychoanalytic research, the purpose of creating a subtype of body dysmorphic disorder, as well as searching to recognize which kind of discourse is within symptom social bond of that individuals who show a clear distortion in their body image, which make them feel weak and small, when, in fact, they are very strong and brawny, leading them into an obsession to reach a “perfect” body. From such subjects’ relationship with wish and enjoyment, this study argues on the relationship between overtraining and current imperatives of enjoyment focusing on a male body that is brawny and in shape. The study considers that one cannot talk about overtraining as a category to psychoanalysis, since it has to be treated as a symptom; as an expression of cultural distress; as a manifestation of enjoyment real, that comes back; as a contemporary way man found for questioning about maleness; and, primarily, as a way subject finds to face civilizatory ideals that require body’s surrendering. The research concludes that freudo-lacanian psychoanalysis can introduce a theorization on such symptomatology etiology, without needing to create new categories, both inside theory, or to use psychiatric categorization. The work shows a straight articulation between the graduating student discourse and the overtraining symptoms, but it is not possible to assert that individuals showing overtraining symptoms are necessarily obsessive neurotic, although there can be a strong appeal for obsessions formation within searching for ideal body. In such sense, the study designs a discussion on how overtraining symptoms can emerge within obsessive neurosis and hysteria, not excluding its possibility to be present in perversion or psychosis. / A pesquisa trata da dismorfia muscular, também denominada vigorexia. Considera-se que a ‘vigorexia’ não é um conceito psicanalítico, mas que é possível aproximar-se deste mediante a Psicanálise freudo-lacaniana. Assim, o objetivo é analisar com base na teoria psicanalítica a proposta de criação, pela Psiquiatria, desse subtipo do já descrito transtorno dismórfico corporal, além de procurar perceber que tipo de discurso está presente no laço social do sintoma desses indivíduos que apresentam clara distorção na imagem de corpo que os faz se acharem pequenos e fracos, quando na verdade são bastante fortes e musculosos conduzindo-os a uma obsessão por atingir o corpo ‘perfeito’. Animado na relação desses sujeitos com o desejo e com o gozo, aborda-se a relação da vigorexia e os imperativos de gozo hodiernos em sua ênfase ao corpo masculino musculoso e definido. Considera-se que não se pode falar da vigorexia como categoria para a Psicanálise, pois se deve tratá-la como um sintoma, uma expressão do mal-estar na cultura, manifestação do real de gozo que retorna como uma forma hodierna de o homem se interrogar quanto à masculinidade, sobretudo como maneira de o sujeito fazer frente aos ideais civilizatórios que exigem a renúncia do gozo. Conclui-se que a Psicanálise freudo-lacaniana pode apresentar uma teorização sobre a etiologia dessa sintomatologia, sem a necessidade de recorrer à criação de novas categorias, seja no interior da teoria, seja para utilizar-se da classificação psiquiátrica. Percebeu-se estreita articulação entre o discurso do universitário e os sintomas vigoréxicos, sem, no entanto, ser possível asseverar que indivíduos com sintomas vigoréxicos sejam necessariamente neuróticos obsessivos; mas que, na adicção ao exercício físico como busca de um corpo ideal, há questões que podem fazer forte empuxo à formação de obsessões. Nesse sentido, elabora-se uma discussão de como os sintomas vigoréxicos podem comparecer nas neuroses obsessiva e na histeria, sem excluir a possibilidade de que ela possa estar presente na perversão ou na psicose.

Made available in DSpace on 2014-06-11T19:31:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-26Bitstream added on 2014-06-13T19:41:07Z : No. of bitstreams: 1 souza_ap_dr_jabo.pdf: 811812 bytes, checksum: 25bce5312ab6b25601cdee2a32e17491 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A Distrofia Muscular de Duchenne (DMD) é uma doença genética recessiva e hereditária, ligada ao cromossomo X, caracterizada pela ausência ou insuficiência da proteína distrofina no sarcolema das fibras musculares. É uma doença muscular progressiva, que afeta um em cada 3.500 meninos. Atualmente, os cães da raça Golden Retriever, portadores da distrofia muscular do Golden Retriever (GRMD), que exibem mudanças musculares, patogenia, bem como o fenótipo, comparáveis aos vistos nos casos de DMD, vêm sendo considerados o melhor modelo animal para o estudo da DMD. Nos GRMDs a fraqueza muscular inicia-se a partir do segundo mês de vida e é progressiva, portanto, a expectativa de vida destes cães é muito reduzida. Histologicamente, os músculos mostram necrose, fibrose e regeneração. As manifestações patológicas da GRMD já se iniciam na vida intra-uterina com o desenvolvimento de lesões nos músculos da língua. A hipertrofia da língua está associada com disfunção da faringe e do esôfago, o que resulta em disfagia, regurgitação e sialorréia. A pesquisa com células-tronco tem um potencial para avanços significativos no nosso conhecimento da diferenciação celular com a promessa de excitantes e inovadoras aplicações terapêuticas para desordens genéticas e degenerativas incuráveis... / Duchenne’s Muscular Dystrophy (DMD) is a lethal childhood disease, a X-linked recessive disorder, caused by mutations of the dystrophyn gene, a protein that has a vital role in maintaining muscle structure and function. DMD is a progressive muscular disease, that affects 1:3500 born boys. At this moment, the dogs with Golden Retriever Muscular Dystrophy (GRMD), is the best animal model to study DMD. GRMD dog exhibits muscle changes, pathogenesis and phenotype comparable with the DMD boys. In GRMDs the muscular weakness beginning with 60 days of life and this is progressive. Histologically, the muscles show necrosis, fibrosis, degeneration and regeneration. The pathogenesis manifests in utero with the development of lingual muscle lesions. The tongue hypertrophy is associated with pharyngeal and esophageal dysfunction, and results in dysphagia, regurgitation and drooling. The research with steam-cells has a great potential to significative advances in owner knowledge about cellular differentiation, with the promise of therapeutic applications in genetic disorders and in degenerative or incurable diseases...(Complete abstract, click electronic access below)

Made available in DSpace on 2014-06-11T19:33:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T21:06:06Z : No. of bitstreams: 1 miyazato_lg_dr_jabo.pdf: 12108110 bytes, checksum: 389387edb66af6afc5029abc0101e08a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Fatec / O objetivo deste estudo foi o de caracterizar lesões musculares em cães com Distrofia Muscular do golden retriever (DMGR), de diferentes idades, por análises histopatológica e imunoistoquímica. Foram utilizados vinte e cinco cães machos classificados e distribuídos em grupos de acordo com a idade: grupo I – distróficos até 1 ano; grupo II – distróficos acima de 1 ano; grupo III - controle até 1 ano; grupo IV - controle acima de 1 ano. Uma amostra de cada músculo foi fixada em solução de formol, processadas pelas técnicas usuais de inclusão em parafina, coradas com HE e TGM para análise histopatológica e processadas para a análise imunoistoquímica de linfócitos T-CD3+, antígeno MHC II e vimentina. Outras amostras foram congeladas em nitrogênio líquido e processadas pelas técnicas usuais para realização das reações imunoistoquímicas para marcação dos linfócitos T-CD4+, TCD8+ e do antígeno MHC I. Os resultados mostraram que as lesões nos músculos distróficos do grupo I foram moderadas comparativamente às do grupo II que foram severas. Nos músculos distróficos, os linfócitos T-CD3+, T-CD4+ e T-CD8+ concentravam-se nas áreas de degeneração e necrose. O número de linfócitos T-CD3+ e T-CD4+ foi significativamente maior (p < 0.05) em todos os músculos distróficos em comparação aos controles, demonstrando a participação dos linfócitos T na doença. O número de linfócitos T-CD8+ foi significativamente maior (p < 0.05) nos distróficos, exceto para os músculos sartório cranial no grupo I, diafragma e bíceps femoral no grupo II. A imunoexpressão do MHC I intensificou-se com a idade nos animais distróficos, ao contrário do MHC II que se manteve. A imunoexpressão da vimentina e do VEGF nos músculos distróficos foi discreta (escore 1) em todos os músculos avaliados. Destes resultados podemos... / The purpose of this study was to characterize the lesions in dystrophic muscles of DMGR dogs of different ages, by means of histopathological and immunohistochemistry analysis. Twenty-five male dogs were classified and distributed into groups according to the age: Group I - dystrophic up to 1 year, group II - dystrophic over 1 year, group III - control up to 1 year, group IV - control over 1 year. One sample from each muscle was fixed in formalin solution, processed by usual techniques of paraffin embedding, stained with HE and TGM for histopathological purposes and processed for immunohistochemical analysis of the distribution of T-lymphocytes CD3+, MHC II and vimentin. Other samples were frozen in liquid nitrogen, processed by usual techniques of freezing in order to perform the techniques of immunohistochemical labelling for CD4+ T-lymphocytes, T-CD8+ and MHC I. The results of histopathological analysis showed that the lesions in dystrophic muscles in the Group I were moderate compared to that ones in the Group II which were severe. The CD3+, CD4+ and CD8+ Tlymphocytes were more numerous in dystrophic muscles especially in areas of degeneration and necrosis. The number of CD3+ and CD4+ T-lymphocytes was found to be significantly higher (p <0.05) in all dystrophic muscles compared to controls demonstrating the involvement of T-lymphocytes in the disease. The number of CD8+ Tlymphocytes was found to be significantly higher (p <0.05) in dystrophics, except for the cranial sartorius muscles in the Group I and the diaphragm and biceps femoris in the Group II. The immunoexpression of MHC I increased with age in dystrophic animals, in contrast to MHC II that remained the same. The immunoexpression of vimentin and VEGF in the dystrophic muscles was mild (score 1) upon all muscles. From these results we can conclude that in dystrophic muscle immunoexpression of... (Complete abstract click electronic access below)

Orientadora: Mirela Bonafim Carvalho / Banca: Carlos Roberto Daleck / Banca: Wilter Ricardo Russiano Vicente / Banca: Maria Angélica Miglino / Banca: Carlos Eduardo Ambrósio / Resumo: A Distrofia Muscular de Duchenne (DMD) é uma doença genética recessiva e hereditária, ligada ao cromossomo X, caracterizada pela ausência ou insuficiência da proteína distrofina no sarcolema das fibras musculares. É uma doença muscular progressiva, que afeta um em cada 3.500 meninos. Atualmente, os cães da raça Golden Retriever, portadores da distrofia muscular do Golden Retriever (GRMD), que exibem mudanças musculares, patogenia, bem como o fenótipo, comparáveis aos vistos nos casos de DMD, vêm sendo considerados o melhor modelo animal para o estudo da DMD. Nos GRMDs a fraqueza muscular inicia-se a partir do segundo mês de vida e é progressiva, portanto, a expectativa de vida destes cães é muito reduzida. Histologicamente, os músculos mostram necrose, fibrose e regeneração. As manifestações patológicas da GRMD já se iniciam na vida intra-uterina com o desenvolvimento de lesões nos músculos da língua. A hipertrofia da língua está associada com disfunção da faringe e do esôfago, o que resulta em disfagia, regurgitação e sialorréia. A pesquisa com células-tronco tem um potencial para avanços significativos no nosso conhecimento da diferenciação celular com a promessa de excitantes e inovadoras aplicações terapêuticas para desordens genéticas e degenerativas incuráveis...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Duchenne's Muscular Dystrophy (DMD) is a lethal childhood disease, a X-linked recessive disorder, caused by mutations of the dystrophyn gene, a protein that has a vital role in maintaining muscle structure and function. DMD is a progressive muscular disease, that affects 1:3500 born boys. At this moment, the dogs with Golden Retriever Muscular Dystrophy (GRMD), is the best animal model to study DMD. GRMD dog exhibits muscle changes, pathogenesis and phenotype comparable with the DMD boys. In GRMDs the muscular weakness beginning with 60 days of life and this is progressive. Histologically, the muscles show necrosis, fibrosis, degeneration and regeneration. The pathogenesis manifests in utero with the development of lingual muscle lesions. The tongue hypertrophy is associated with pharyngeal and esophageal dysfunction, and results in dysphagia, regurgitation and drooling. The research with steam-cells has a great potential to significative advances in owner knowledge about cellular differentiation, with the promise of therapeutic applications in genetic disorders and in degenerative or incurable diseases...(Complete abstract, click electronic access below) / Doutor

Atualmente, a espectroscopia de Ressonância Magnética Nuclear (RMN) in vitro tem sido extensivamente empregada para estudar tecidos biológicos, atuando como uma poderosa ferramenta de análise química. Em particular, a RMN de próton (1H) e de fósforo (31P) vem sendo utilizada para estudar o metabolismo muscular de animais portadores de deficiências genéticas, como os camundongos com distrofia muscular mdx, modelos para a distrofia muscular Duchenne (DMD). A DMD, que afeta humanos, é um distúrbio recessivo ligado ao cromossomo-X e ocorre em 1 para cada 3500 nascidos vivos do sexo masculino. A DMD é caracterizada pela ausência da proteína distrofina, o que provoca um processo progressivo e rápido de degeneração muscular. Atualmente, o acompanhamento da evolução da doença e de benefícios de tratamentos é feito através de biópsias do tecido muscular. Neste estudo foram realizadas medidas de RMN de 1H em amostras de diafragma e do músculo quadríceps femural de camundongos mdx e de controle com 3 e 6 meses de idade. Os resultados foram comparados com a análise histológica dos mesmos tecidos. O objetivo deste trabalho é monitorar o desenvolvimento normal dos músculos de animais de controle e o progresso da distrofia nos músculos de animais mdx, através da análise dos espectros de RMN. Foi possível identificar diferenças entre os grupos de animais a partir das integrais dos picos observados, mostrando que a distrofia acarreta alterações em diversas vias metabólicas nos camundongos mdx. Estes resultados formam a base para estudos da doença in vivo, para que então seja possível diferenciar músculos distróficos de músculos sadios e caracterizar diferentes estágios de evolução da doença de maneira não invasiva. / Currently, Nuclear Magnetic Resonance spectroscopy in vitro has been extensively used to study biological tissues, acting as a powerful tool for chemical analysis. In particular, NMR of proton (1H) and phosphorus (31P) has been used to study muscle metabolism in animals with genetic diseases, such as mice with muscular dystrophy mdx, models for Duchenne muscular dystrophy (DMD). The DMD, which affects humans, is a recessive disorder linked to X-chromosome and occurs in 1 each 3,500 live births male. The DMD is characterized by the absence of dystrophin protein, which causes a progressive and rapid degeneration. Currently, the monitoring of disease progression and benefits of treatments is made by biopsy of muscle tissue. In this study, 1H NMR spectrum were acquired from samples of diaphragm and quadriceps muscle of mdx and control mice 3 or 6 months-old. Results were compared with histological analysis of the same tissues. The objective of this study is to monitor the normal development of the muscles of control animals and the progress of dystrophy in the muscles of mdx animals by analyzing the NMR spectra. Differences were found between the groups of animals comparing the integrals of the observed peaks, showing that dystrophy leads to alterations in several methabolic pathways in the mdx mouse. These results form the basis for studies of the disease in vivo, so then it can be possible to distinguish dystrophic muscles from healthy muscles and characterize different stages of the disease noninvasively.

O objetivo do presente estudo foi avaliar a aptidão reprodutiva de cães da raça Golden Retriever afetados pela distrofia muscular. Realizou-se avaliações andrológicas em 11 cães com idades entre 10 meses e 4 anos. Destes, 7 eram afetados pela distrofia muscular e 4 sadios, utilizados como controle. Todos foram submetidos a exame clinico, análise seminal e ultra-sonografia dos órgãos reprodutores. Analisou-se também a morfologia dos testículos e seus respectivos funículos espermáticos dos cães que foram a óbito. Detectou-se as seguintes alterações nos cães afetados pela distrofia: atrofia muscular, andar rígido, pneumonia por aspiração, fragilidade do diafragma com projeção do estomago para a cavidade torácica, megaesôfago e cardiomiopatia dilatada. Em relação aos órgãos genitais dois dos cães apresentaram criptorquidismo bilateral. Os resultados das análises seminais mostraram que os cães afetados pela distrofia possuem maior quantidade de defeitos espermáticos maiores e totais. Nas avaliações ultra-sonográficas não foram identificadas diferenças entre os cães afetados pela distrofia quando comparados com cães sadios. As análises histopatológicas evidenciaram alterações morfológicas nos testículos e músculos cremáster de cães afetados pela doença. Os testículos apresentaram degeneração testicular e o músculo cremáster retração de fibras musculares com hialinizacao dos miócitos. Conclui-se então que a distrofia muscular em cães da raça Golden Retriever pode comprometer sua aptidão reprodutiva. / The aim of the present research was to evaluate the reproductive condition of Golden Retriever dogs affected by muscular dystrophy. Breeding soundness examination was performed in 11 male dogs aged between 10 months and 4 years. Seven of this total were affected by muscular dystrophy and 4 healthy dogs that served as control. All dogs were submitted to a through physical exam, seminal evaluation and ultrasound of the reproductive tract. Testicle and spermatic cord morphology of post-mortem dogs were also examined. The following alterations were observed for the affected dogs: muscular atrophy, stiff walk, aspiration pneumonia, diaphragmatic fragility with stomach projection to the torax, megaesophagus e dilated cardiomyopathy. In relation to the genital tract, two dogs presented with bilateral cryptorchidism. Semen evaluation revealed high percentage of major and total sperm defects in affected dogs. Ultrasonographic exams were similar among healthy and affected dogs. Histophatology of the testicle and cremaster muscle revealed morphologic alterations in affected dogs represented by degeneration and muscular retraction with miocyte hyalinization, respectively. In conclusion, affected Golden Retriever dogs have their reproductive performance compromised by the muscular dystrophy.