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

The toroidal field coil design for ARIES-ST

An evolutionary process was used to develop the toroidal field (TF) coil design for the ARIES-ST (Spherical Tokamak). Design considerations included fabricability, assembly, maintenance, energy efficiency, and structural robustness. The design addresses a number of the concerns (complexity) and criticisms (high cost, high recirculating power) of fusion. It does this by: (1) Applying advanced, but available laser forming and spray casting techniques for manufacturing the TF coil system; (2) Adopting a simple single toroidal field coil system to make assembly and maintenance much easier, the single turn design avoids the necessity of using the insulation as a structural component of the TF coils, and hence is much more robust than multi-turn designs; and (3) Using a high conductivity copper alloy and modest current densities to keep the recirculating power modest

Next Step Spherical Torus Design Studies

Studies are underway to identify and characterize a design point for a Next Step Spherical Torus (NSST) experiment. This would be a ''Proof of Performance'' device which would follow and build upon the successes of the National Spherical Torus Experiment (NSTX) a ''Proof of Principle'' device which has operated at PPPL since 1999. With the Decontamination and Decommissioning (D&D) of the Tokamak Fusion Test Reactor (TFTR) nearly completed, the TFTR test cell and facility will soon be available for a device such as NSST. By utilizing the TFTR test cell, NSST can be constructed for a relatively low cost on a short time scale. In addition, while furthering spherical torus (ST) research, this device could achieve modest fusion power gain for short-pulse lengths, a significant step toward future large burning plasma devices now under discussion in the fusion community. The selected design point is Q=2 at HH=1.4, P subscript ''fusion''=60 MW, 5 second pulse, with R subscript ''0''=1.5 m, A=1.6, I subscript ''p''=10vMA, B subscript ''t''=2.6 T, CS flux=16 weber. Most of the research would be conducted in D-D, with a limited D-T campaign during the last years of the program

Silent polymorphisms in the RYR1 gene do not\ud modify the phenotype of the p.4898 I>T\ud pathogenic mutation in central core disease:\ud a case report

Background: Central core disease is a congenital myopathy, characterized by presence of central core-like areas in\ud muscle fibers. Patients have mild or moderate weakness, hypotonia and motor developmental delay. The disease is\ud caused by mutations in the human ryanodine receptor gene (RYR1), which encodes a calcium-release channel.\ud Since the RYR1 gene is huge, containing 106 exons, mutation screening has been limited to three ‘hot spots’, with\ud particular attention to the C-terminal region. Recent next- generation sequencing methods are now identifying\ud multiple numbers of variants in patients, in which interpretation and phenotype prevision is difficult.\ud Case presentation: In a Brazilian Caucasian family, clinical, histopathological and molecular analysis identified a\ud new case of central core disease in a 48-year female. Sanger sequencing of the C-terminal region of the RYR1\ud gene identified two different missense mutations: c.14256 A > C polymorphism in exon 98 and c.14693 T > C in\ud exon 102, which have already been described as pathogenic. Trans-position of the 2 mutations was confirmed\ud because patient’s daughter, mother and sister carried only the exon 98’s mutation, a synonymous variant that was\ud subsequently found in the frequency of 013–0,05 of alleles. Further next generation sequencing study of the whole\ud RYR1 gene in the patient revealed the presence of additional 5 common silent polymorphisms in homozygosis and\ud 8 polymorphisms in heterozygosis.\ud Conclusions: Considering that patient’s relatives showed no pathologic phenotype, and the phenotype presented\ud by the patient is within the range observed in other central core disease patients with the same mutation, it was\ud concluded that the c.14256 A > C polymorphism alone is not responsible for disease, and the associated additional\ud silent polymorphisms are not acting as modifiers of the primary pathogenic mutation in the affected patient. The\ud case described above illustrates the present reality where new methods for wide genome screening are becoming\ud more accessible and able to identify a great variety of mutations and polymorphisms of unknown function in\ud patients and their families.Fundação de Amparo a Pesquisa do Estado de São Paulo - Centro de Pesquisa, Inovação e Difusão (FAPESP-CEPID)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-INCT)Associação Brasileira de Distrofia Muscular (ABDIM)CAPES-COFECU

Spherical Torus Center Stack Design

The low aspect ratio spherical torus (ST) configuration requires that the center stack design be optimized within a limited available space, using materials within their established allowables. This paper presents center stack design methods developed by the National Spherical Torus Experiment (NSTX) Project Team during the initial design of NSTX, and more recently for studies of a possible next-step ST (NSST) device

Contamination of Mesenchymal Stem-Cells with Fibroblasts Accelerates Neurodegeneration in an Experimental Model of Parkinson’s Disease

Pre-clinical studies have supported the use of mesenchymal stem cells (MSC) to treat highly prevalent neurodegenerative diseases such as Parkinson’s disease (PD) but preliminary trials have reported controversial results. In a rat model of PD induced by MPTP neurotoxin, we first observed a significant bilateral preservation of dopaminergic neurons in the substantia nigra and prevention of motor deficits typically observed in PD such as hypokinesia, catalepsy, and bradykinesia, following intracerebral administration of human umbilical cord-derived MSC (UC-MSC) early after MPTP injury. However, surprisingly, administration of fibroblasts, mesenchymal cells without stem cell properties, as a xenotransplantation control was highly detrimental, causing significant neurodegeneration and motor dysfunction independently of MPTP. This observation prompted us to further investigate the consequences of transplanting a MSC preparation contaminated with fibroblasts, a plausible circumstance in cell therapy since both cell types display similar immunophenotype and can be manipulated in vitro under the same conditions. Here we show for the first time, using the same experimental model and protocol, that transplantation of UC-MSC induced potent neuroprotection in the brain resulting in clinical benefit. However, co-transplantation of UC-MSC with fibroblasts reverted therapeutic efficacy and caused opposite damaging effects, significantly exacerbating neurodegeneration and motor deficits in MPTP-exposed rats. Besides providing a rationale for testing UC-MSC transplantation in early phases of PD aiming at delaying disease progression, our pre-clinical study suggests that fibroblasts may be common cell contaminants affecting purity of MSC preparations and clinical outcome in stem cell therapy protocols, which might also explain discrepant clinical results

Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance

The present investigation was undertaken to test whether exercise training (ET) associated with AMPK/PPAR agonists (EM) would improve skeletal muscle function in mdx mice. These drugs have the potential to improve oxidative metabolism. This is of particular interest because oxidative muscle fibers are less affected in the course of the disease than glycolitic counterparts. Therefore, a cohort of 34 male congenic C57Bl/10J mdx mice included in this study was randomly assigned into four groups: vehicle solution (V), EM [AICAR (AMPK agonist, 50 mg/Kg-1.day-1, ip) and GW 1516 (PPAR delta agonist, 2.5 mg/Kg-1.day-1, gavage)], ET (voluntary running on activity wheel) and EM+ET. Functional performance (grip meter and rotarod), aerobic capacity (running test), muscle histopathology, serum creatine kinase (CK), levels of ubiquitined proteins, oxidative metabolism protein expression (AMPK, PPAR, myoglobin and SCD) and intracellular calcium handling (DHPR, SERCA and NCX) protein expression were analyzed. Treatments started when the animals were two months old and were maintained for one month. A significant functional improvement (p<0.05) was observed in animals submitted to the combination of ET and EM. CK levels were decreased and the expression of proteins related to oxidative metabolism was increased in this group. There were no differences among the groups in the intracellular calcium handling protein expression. To our knowledge, this is the first study that tested the association of ET with EM in an experimental model of muscular dystrophy. Our results suggest that the association of ET and EM should be further tested as a potential therapeutic approach in muscular dystrophies.Fundacao de Amparo a Pesquisa do Estado de Sao PauloFundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP - CEPID 98/14254-2]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Instituto Nacional de Ciencia e Tecnologia (INCT)Instituto Nacional de Ciencia e Tecnologia (INCT