Muscular dystrophy-related quantitative and chemical changes in adenohypophysis GH-cells in golden retrievers

Lima, Andressa; Nyengaard, Jens Randel; Jorge, Alexander A L; Balieiro, J. C. C.; Peixoto, Clayton; Fioretto, Emerson Ticona; Ambrósio, Carlos Eduardo; Miglino, María Angélica; Zatz, Mayana; Ribeiro, Antônio Augusto Coppi Maciel

doi:10.1016/j.ghir.2007.06.001

Cited by 21 publications

(16 citation statements)

References 43 publications

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“…Moreover, in a separate GRMD study, lower growth hormone levels actually tended to correlate with a more severe phenotype (de Lima et al 2007). In reviewing our own phenotypic data, we found that larger GRMD dogs, if anything, have milder signs at 6 months of age.…”

Section: Biomarkers For Assessment Of the Natural History And Responsmentioning

confidence: 87%

Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies

et al. 2012

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Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder in which the loss of dystrophin causes progressive degeneration of skeletal and cardiac muscle. Potential therapies that carry substantial risk, such as gene and cell-based approaches, must first be tested in animal models, notably the mdx mouse and several dystrophin-deficient breeds of dogs, including golden retriever muscular dystrophy (GRMD). Affected dogs have a more severe phenotype, in keeping with that of DMD, so may better predict disease pathogenesis and treatment efficacy. We and others have developed various phenotypic tests to characterize disease progression in the GRMD model. These biomarkers range from measures of strength and joint contractures to magnetic resonance imaging. Some of these tests are routinely used in clinical veterinary practice, while others require specialized equipment and expertise. By comparing serial measurements from treated and untreated groups, one can document improvement or delayed progression of disease. Potential treatments for DMD may be broadly categorized as molecular, cellular, or pharmacologic. The GRMD model has increasingly been used to assess efficacy of a range of these therapies. While some of these studies have largely provided general proof-of-concept for the treatment under study, others have demonstrated efficacy using the biomarkers discussed. Importantly, just as symptoms in DMD vary among patients, GRMD dogs display remarkable phenotypic variation. While confounding statistical analysis in preclinical trials, this variation offers insight regarding the role that modifier genes play in disease pathogenesis. By correlating functional and mRNA profiling results, gene targets for therapy development can be identified.

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Section: Biomarkers For Assessment Of the Natural History And Responsmentioning

confidence: 87%

Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies

et al. 2012

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“…The total volumes occupied by the thoracic aorta compartments (V COMP ) were estimated indirectly by multiplying their fractional volumes (V vCOMP ) by the thoracic aorta volume (V TA ) [25]. …”

Section: Methodsmentioning

confidence: 99%

Exercise Training Restores Hypertension-Induced Changes in the Elastic Tissue of the Thoracic Aorta

et al. 2011

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Background/Aims: Pharmacological antihypertensive therapies decrease both wall hypertrophy and collagen, but are unable to diminish the elastic content in the thoracic aorta. We investigated the effects of exercise training on aortic structure and function. Methods: Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), submitted to low-intensity training (T) or kept sedentary (S), were subjected to haemodynamic analyses. The thoracic aorta was processed for real-time PCR, light (morphometric/stereological evaluations) and electron microscopy. Results: SHR_S versus WKY_S exhibited a higher heart rate, pressure and pulse pressure, increased α-actin, elastin and collagen mRNA expression, augmented wall volume and cross-sectional area (marked elastin/collagen content). In the SHR, training reduced pressure and heart rate, with slight reduction in pulse pressure. SHR_T aortas exhibited small morphometric changes, reduced α-actin, elastin and collagen mRNA expression, normalization of increased elastic content, reduction in collagen/connective tissue and a decrease in smooth muscle cell volume (p < 0.05 for all comparisons). SHR_T aortas showed improved circumferential orientation of smooth muscle cells and prevention of rupture/duplication of internal elastic lamina. No effects were observed in trained WKY aortas. Conclusions: Training effectively corrects elastic, collagen and smooth muscle content in SHR aortas. These changes, by reducing aortic pulsatility, facilitate a buffering function and reduce the cardiovascular risk.

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“…For electron microscopy, we followed the descriptions of the Lima et al (2007), briefly, samples were fixed in Karnovsky solution (5% glutaraldehyde, 1% formaldehyde) in sodium cacodylate buffer (0.125M; pH 7.4) for 72h and, dehydrated in a crescent series of ethanol and, embedded in Spurr epoxy resin (ProSciTech, Queensland). Ultrathin sections were obtained at 70-90nm on a Leica Ultracut UCT, and collected in a 200 mesh-grid.…”

Section: Methodsmentioning

confidence: 99%

Establishment of a protocol for obtention of neuronal stem cells lineages from the dog olfactory epithelium

et al. 2010

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Miglino M.A. 2010. Establishment of a protocol for obtention of neuronal stem cells lineages from the dog olfactory epithelium. Pesquisa . Departamento de Ciência Animal, Campus Universitário, Bairro Cibrazen, Bom Jesus, PI 64900-000, Brazil. E-mail: flavioribeiro@ufpi.edu.br A morphological and cell culture study from nasal mucosa of dogs was performed in order to establish a protocol to obtain a cell population committed to neuronal lineage, as a proposal for the treatment of traumatic and degenerative lesions in these animals, so that in the future these results could be applied to the human species. Twelve mongrel dogs of 60-day aged pregnancy were collected from urban pound dogs in São Paulo. Tissue from cribriform ethmoidal lamina of the fetuses was collected at necropsy under sterile conditions around 1h to 2h postmortem by uterine sections and sections from the fetal regions described above. Isolated cells of this tissue were added in DMEM/F-12 medium under standard conditions of incubation (5% CO 2 , >37°C). Cell culture based on isolated cells from biopsies of the olfactory epithelium showed rapid growth when cultured for 24 hours, showing phase-bright sphere cells found floating around the fragments, attached on culture flasks. After 20 days, a specific type of cells, predominantly ellipsoids or fusiform cells was characterized in vitro. The indirect immunofluorescence examination showed cells expressing markers of neuronal precursors (GFAP, neurofilament, oligodendrocyte, and III â-tubulin). The cell proliferation index showed Ki67 immunostaining with a trend to label cell groups throughout the apical region, while PCNA immunostaining label predominantly cell groups lying above the basal lamina. The transmission electron microscopy from the olfactory epithelium of dogs revealed cells with electron-dense cytoplasm and preserving the same distribution as those of positive cell staining for PCNA. Metabolic activity was confirmed by presence of euchromatin in the greatest part of cells. All these aspects give subsidies to support the hypothesis about resident progenitor cells among the basal cells of the olfactory epithelium, committed to renewal of these cell populations, especially neurons. RESUMO.-[Estabelecimento de um protocolo para obtenção de linhagens de células-tronco neuronais a partir do epitélio olfatório de cães.] Foi realizado um estudo morfológico e por cultivo celular a partir de células provenientes da mucosa olfatória de cães, como forma de estabelecer um protocolo de cultivo, como uma proposta para o tratamento de lesões traumáticas e nervosas degenerativas nestes animais e futuramente, para que tais resultados possam ser aplicados a espécie humana. Foram utilizados doze cães sem raça definida, a termo, oriundos de castrações do Centro de Controle de Zoonoses de São Paulo. O tecido da lâmina cribiforme do etmóide dos fetos foi coletado sob necropsia, em condições estéreis, 1 a 2 horas post mortem, por meio de incisão uterina e acesso da região fetal supracitada. Depois as células isol...

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Muscular dystrophy-related quantitative and chemical changes in adenohypophysis GH-cells in golden retrievers

Cited by 21 publications

References 43 publications

Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies

Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies

Exercise Training Restores Hypertension-Induced Changes in the Elastic Tissue of the Thoracic Aorta

Establishment of a protocol for obtention of neuronal stem cells lineages from the dog olfactory epithelium

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