Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation I as augmentation therapeutic strategy approaches in muscular dystrophy

Backgrond: Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. Methods: In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. Results: The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

Potential ultrastructural changes in rat epididymal cell types induced by Boswellia papyrifera and Boswellia carterii incense

Boswellia papyrifera and Boswellia carterii, known as Arabian incense, diffuses smoke, contaminating the air, which adversely affects human health. Therefore, this study was designed to ascertain the effect of these plants on histopathological and ultrastructure changes in cauda epididymis of Albino rats. Animals were exposed to 4 g/kg body weight of B. papyrifera and B. carterii daily for 120 days along with suitable controls. Our study indicates a significant reduction in epithelial heights. Cells showed signs of degeneration. The ultrastructural study revealed that the cauda epididymis was affected, including its cell types. Furthermore, a decrease in the size of mitochondria, Golgi complex, and both ERs was observed. In all treated groups, plasma fructose decreased considerably, indicating the sign of reduced energy, vital for motility and other sperm functions. The results of this study suggest that these plants systematically affect cauda epididymal cell types and its lumen through its potential toxicity. (C) 2013 Published by Elsevier Masson SAS on behalf of Academie des sciences.

Drosophila Erect wing (Ewg) controls mitochondrial fusion during muscle growth and maintenance by regulation of the Opa1-like gene

Mitochondrial biogenesis and morphological changes are associated with tissue-specific functional demand, but the factors and pathways that regulate these processes have not been completely identified. A lack of mitochondrial fusion has been implicated in various developmental and pathological defects. The spatiotemporal regulation of mitochondrial fusion in a tissue such as muscle is not well understood. Here, we show in Drosophila indirect flight muscles (IFMs) that the nuclear-encoded mitochondrial inner membrane fusion gene, Opa1-like, is regulated in a spatiotemporal fashion by the transcription factor/co-activator Erect wing (Ewg). In IFMs null for Ewg, mitochondria undergo mitophagy and/or autophagy accompanied by reduced mitochondrial functioning and muscle degeneration. By following the dynamics of mitochondrial growth and shape in IFMs, we found that mitochondria grow extensively and fuse during late pupal development to form the large tubular mitochondria. Our evidence shows that Ewg expression during early IFM development is sufficient to upregulate Opa1-like, which itself is a requisite for both late pupal mitochondrial fusion and muscle maintenance. Concomitantly, by knocking down Opa1-like during early muscle development, we show that it is important for mitochondrial fusion, muscle differentiation and muscle organization. However, knocking down Opa1-like, after the expression window of Ewg did not cause mitochondrial or muscle defects. This study identifies a mechanism by which mitochondrial fusion is regulated spatiotemporally by Ewg through Opa1-like during IFM differentiation and growth.

Potential histopathological and molecular changes in rat vas deferens inhaled by Boswellia papyrifera and Boswellia carterii

Boswellia papyrifera and Boswellia carterii released from smoke contaminate indoor environment and consequently adversely affect humans as evidenced by respiratory disturbances. The aim of this study was to determine the effects of these plants on pathological and biochemical changes in vas deferens of albino rats. Animals were administered 4g/kg body weight B. papyrifera and B. carterii daily for 120days along with controls. Significant changes were observed in epithelial cell types and some cells showed signs of degeneration. The ultrastructural studies revealed marked changes in cytoplasmic organelles. Microvilli were missing and lysosomes were found in the cytoplasm. In addition, all treated groups plasma fructose and other biochemical parameters were decreased indicating reduced energy necessary for motility and contractility of spermatozoa. Many spermatozoa were disorganized and agglomerated. Data suggest that smoke from these plants adversely affects vas deferens.

Stable isotopic signature of Southern Ocean deep water CO2 ventilation

The link between atmospheric CO2 level and ventilation state of the deep ocean is poorly understood due to the lack of coherent observations on the partitioning of carbon between atmosphere and ocean. In this Southern Ocean study, we have classified the Southern Ocean into different zones based on its hydrological features and have binned the variability in latitudinal air-CO2 concentration and its isotopic ratios. Together with air-CO2, we analysed the surface water for the isotopic ratios in dissolved inorganic carbon (DIC). Using the binary mixing approach on the isotopic ratio of atmospheric CO2 and its concentration, we identified the delta C-13 value of source CO2. The isotopic composition of source CO2 was around -9.22 +/- 0.26 parts per thousand for the year 2011 and 2012, while a composition of -13.49 +/- 4.07 parts per thousand was registered for the year 2013. We used the delta C-13 of DIC to predict the CO2 composition in air under equilibrium and compared our estimates with actual observations. We suggest that the degeneration of the DIC in presence of warm water in the region was the factor responsible for adding the CO2 to the atmosphere above. The place of observation coincides with the zone of high wind speed which promotes the process of CO2 exsolution from sea water. (C) 2015 Elsevier Ltd. All rights reserved.

Aspectos bioéticos del trasplante con donantes vivos

Resumen: El 4 de junio de 2010 se solicita al Comité de Bioética del Hospital Privado de Córdoba, Argentina, una consulta para que se analicen los aspectos éticos de un trasplante pulmonar lobar bilateral, con donante vivo relacionado para dos hermanas gemelas de 17 años con diagnóstico de fibrosis quística (Acta 172). Este caso nos permite revisar dos ejes esenciales de la constitución de la Bioética como son las funciones y actuación de los comités de Bioética en las instituciones hospitalarias, y la licitud de los trasplantes de órganos cuando hay donantes vivos. Se justificará la actuación del Comité de Bioética en este caso, analizando los puntos a tener en cuenta y los recaudos y recomendaciones que habrían de considerarse frente a esta situación planteada.

Summary report on water quantity and quality studies of Vancouver Lake, Washington

Vancouver Lake, located adjacent to the Columbia River and just north of the Vancouver-Portland metropolitan area, is a "dying" lake. Although all lakes die naturally in geologic time through the process of eutrophication,* Vancouver Lake is dying more rapidly due to man's activities and due to the resultant increased accumulation of sediment, chemicals, and wastes. Natural eutrophication takes thousands of years, whereas man-made modifications can cause the death of a lake in decades. Vancouver Lake does, however, have the potential of becoming a valuable water resource asset for the area, due particularly to its location near the Columbia River which can be used as a source of "flushing" water to improve the quality of Vancouver Lake. (Document pdf contains 59 pages) Community interest in Vancouver Lake has waxed and waned. Prior to World War II, there were relatively few plans for discussions about the Lake and its surrounding land area. A plan to drain the Lake for farming was prohibited by the city council and county commissioners. Interest increased in 1945 when the federal government considered developing the Lake as a berthing harbor for deactivated ships at which time a preliminary proposal was prepared by the City. The only surface water connection between Vancouver Lake and the Columbia River, except during floods, is Lake River. The Lake now serves as a receiving body of water for Lake River tidal flow and surface flow from creeks and nearby land areas. Seasonally, these flows are heavily laden with sediment, septic tank drainage, fertilizers and drainage from cattle yards. Construction and gravel pit operations increase the sediment loads entering the Lake from Burnt Bridge Creek and Salmon Creek (via Lake River by tidal action). The tidal flats at the north end of Vancouver Lake are evidence of this accumulation. Since 1945, the buildup of sediment and nutrients created by man's activities has accelerated the growth of the large water plants and algae which contribute to the degeneration of the Lake. Flooding from the Columbia River, as in 1968, has added to the deposition in Vancouver Lake. The combined effect of these human and natural activities has changed Vancouver Lake into a relatively useless body of shallow water supporting some wildlife, rough fish, and shallow draft boats. It is still pleasant to view from the hills to the east. Because precipitation and streamflow are the lowest during the summer and early fall, water quantity and quality conditions are at their worst when the potential of the Lake for water-based recreation is the highest. Increased pollution of the Lake has caused a larger segment of the community to become concerned. Land use and planning studies were undertaken on the Columbia River lowlands and a wide variety of ideas were proposed for improving the quality of the water-land environment in order to enhance the usefulness of the area. In 1966, the College of Engineering Research Division at Washington State University (WSU0 in Pullman, Washington, was contacted by the Port of Vancouver to determine possible alternatives for restoring Vancouver Lake. Various proposals were prepared between 1966 and 1969. During the summer and fall of 1967, a study was made by WSU on the existing water quality in the Lake. In 1969, the current studies were funded to establish a data base for considering a broad range of alternative solutions for improving the quantity and quality of Vancouver Lake. Until these studies were undertaken, practically no data on a continuous nature were available on Vancouver Lake, Lake River, or their tributaries. (Document pdf contains 59 pages)

Early Functional Deficit and Microglial Disturbances in a Mouse Model of Amyotrophic Lateral Sclerosis

11 p.

Design,optimization and in vivo evaluation of non-viral vectors for gene therapy. Applications in ocular disorders

227 págs.

Novel mechanisms for regulation of cell survival and migration by ceramide 1-phosphate

201 p. : gráf.

Structural Integrity of the Contralesional Hemisphere Predicts Cognitive Impairment in Ischemic Stroke at Three Months

After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror's regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere. Palabras clave

Various algorithms for optimization and learning in adaptive systems

This thesis discusses various methods for learning and optimization in adaptive systems. Overall, it emphasizes the relationship between optimization, learning, and adaptive systems; and it illustrates the influence of underlying hardware upon the construction of efficient algorithms for learning and optimization. Chapter 1 provides a summary and an overview.

Chapter 2 discusses a method for using feed-forward neural networks to filter the noise out of noise-corrupted signals. The networks use back-propagation learning, but they use it in a way that qualifies as unsupervised learning. The networks adapt based only on the raw input data-there are no external teachers providing information on correct operation during training. The chapter contains an analysis of the learning and develops a simple expression that, based only on the geometry of the network, predicts performance.

Chapter 3 explains a simple model of the piriform cortex, an area in the brain involved in the processing of olfactory information. The model was used to explore the possible effect of acetylcholine on learning and on odor classification. According to the model, the piriform cortex can classify odors better when acetylcholine is present during learning but not present during recall. This is interesting since it suggests that learning and recall might be separate neurochemical modes (corresponding to whether or not acetylcholine is present). When acetylcholine is turned off at all times, even during learning, the model exhibits behavior somewhat similar to Alzheimer's disease, a disease associated with the degeneration of cells that distribute acetylcholine.

Chapters 4, 5, and 6 discuss algorithms appropriate for adaptive systems implemented entirely in analog hardware. The algorithms inject noise into the systems and correlate the noise with the outputs of the systems. This allows them to estimate gradients and to implement noisy versions of gradient descent, without having to calculate gradients explicitly. The methods require only noise generators, adders, multipliers, integrators, and differentiators; and the number of devices needed scales linearly with the number of adjustable parameters in the adaptive systems. With the exception of one global signal, the algorithms require only local information exchange.

Wireless parylene-based retinal implant

The degeneration of the outer retina usually causes blindness by affecting the photoreceptor cells. However, the ganglion cells, which consist of optic nerves, on the middle and inner retina layers are often intact. The retinal implant, which can partially restore vision by electrical stimulation, soon becomes a focus for research. Although many groups worldwide have spent a lot of effort on building devices for retinal implant, current state-of-the-art technologies still lack a reliable packaging scheme for devices with desirable high-density multi-channel features. Wireless flexible retinal implants have always been the ultimate goal for retinal prosthesis. In this dissertation, the reliable packaging scheme for a wireless flexible parylene-based retinal implants has been well developed. It can not only provide stable electrical and mechanical connections to the high-density multi-channel (1000+ channels on 5 mm × 5 mm chip area) IC chips, but also survive for more than 10 years in the human body with corrosive fluids.

The device is based on a parylene-metal-parylene sandwich structure. In which, the adhesion between the parylene layers and the metals embedded in the parylene layers have been studied. Integration technology for high-density multi-channel IC chips has also been addressed and tested with dummy and real 268-channel and 1024-channel retinal IC chips. In addition, different protection schemes have been tried in application to IC chips and discrete components to gain the longest lifetime. The effectiveness has been confirmed by the accelerated and active lifetime soaking test in saline solution. Surgical mockups have also been designed and successfully implanted inside dog's and pig's eyes. Additionally, the electrodes used to stimulate the ganglion cells have been modified to lower the interface impedance and shaped to better fit the retina. Finally, all the developed technologies have been applied on the final device with a dual-metal-layer structure.

A regulação política da sexualidade no âmbito da família por saberes e instituições médicas brasileiras : 1838-1940

Esta tese tem como objeto a regulação política da sexualidade no âmbito da família por saberes e instituições médicas brasileiras (1838-1940). Orienta-se pelo interesse em analisar continuidades e descontinuidades na construção de objetos, estratégias e táticas políticas direcionados para a regulação higiênica e eugênica do casamento e da sexualidade infantil. De inspiração foucaultiana, inscreve-se no campo da história dos saberes e está subsidiada por um conjunto heterogêneo de documentos (teses, artigos de periódicos, livros, anais etc.) circunscritos, majoritariamente, ao campo da medicina. Analisa a constituição de uma defesa higiênica dos casamentos no pensamento médico novecentista, voltada para remanejamentos das figuras de esposa e marido na nova configuração de família que começava a se esboçar no Brasil, contrastando-a com a regulação católica da moral sexual colonial. Em seguida, descreve a visibilidade higiênica que a medicina dará a infância no século XIX, problematizando especificamente o interesse pelo tema da masturbação, que articula simultaneamente a família, centrada na figura da mãe, e a escola na convocação de zelar pela criança. Partindo das contradições sociais que se apresentaram na construção do projeto liberal nacional a partir da década de 1870, discute a apropriação do discurso da degenerescência pelo saber médico-psiquiátrico brasileiro, que propiciou uma leitura da brasilidade marcada pelo excesso sexual e pela condição degenerada da miscigenação, a fim de pensar as condições de possibilidade para a emergência do projeto de eugenia matrimonial institucionalizado nas primeiras décadas do século XX e toma como táticas a campanha pela compulsoriedade do exame pré-nupcial, o combate aos casamentos consanguíneos, o controle do contágio venéreo e o aconselhamento sexual dos casais. Analisa a campanha de educação sexual, cuja pretensão de instituir uma sciencia sexual no Brasil, de legitimidade controversa, tinha como horizonte viabilizar uma profilaxia sexual que mitigasse a produção da criminalidade, das perversões sexuais e das doenças nervosas, bem como os desajustes familiares, a partir da fabricação de um novo objeto, qual seja, a sexualidade infantil, no qual incidirá uma nova pedagogia. Nesse particular, aponta particularidades discursivas da difusão das idéias freudianas entre higienistas brasileiros. Finalmente, sinaliza a constituição da higiene mental da criança como um novo domínio para a psiquiatria brasileira, que tomou a intensa circulação afetiva intrafamiliar como ponto de ancoragem para um projeto de normalização social, ainda centrado na eugenia, mas já atravessado por uma psicologia da adaptação.

Relação entre a doença de Parkinson e o gene LRRK2: um estudo na população brasileira

A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais frequente depois da Doença de Alzheimer, afetando aproximadamente 1% da população com idade superior a 65 anos. Clinicamente, esta doença caracteriza-se pela presença de tremor em repouso, bradicinesia, rigidez muscular e instabilidade postural, os quais podem ser controlados com a administração do levodopa. As características patológicas da DP incluem a despigmentação da substância nigra devido à perda dos neurônios dopaminérgicos e a presença de inclusões proteicas denominadas corpos de Lewy nos neurônios sobreviventes. As vias moleculares envolvidas com esta patologia ainda são obscuras, porém a DP é uma doença complexa, resultante da interação entre fatores ambientais e causas genéticas. Mutações no gene leucine-rich repeat kinase 2 (LRRK2; OMIM 609007) constituem a forma mais comum de DP. Este gene codifica uma proteína, membro da família de proteínas ROCO, que possui, entre outros domínios, dois domínios funcionais GTPase (ROC) e quinase (MAPKKK). Neste estudo, os principais domínios do gene LRRK2 foram analisados em 204 pacientes brasileiros com DP por meio de sequenciamento dos produtos da PCR. Através da análise de 14 exons correspondentes aos domínios ROC, COR e MAPKKK foram identificadas 31 variantes. As alterações novas, p.C1770R e p.C2139S, possuem um potencial papel na etiologia da DP. Três alterações exônicas (p.R1398R, p.T1410M e p.Y2189C) e nove intrônicas (c.4317+16C>T, c.5317+59A>C, c.5509+20A>C, c.5509+52T>C, c.5509+122A>G, c.5657-46C>T, c.6382-36G>A, c.6382-37C>T e c.6576+44T>C) são potencialmente não patogênicas. Ao todo, dezessete variantes exônicas e intrônicas constituem polimorfismos já relatados na literatura (p.R1398H, p.K1423K, p.R1514Q, p.P1542S, c.4828-31T>C, p.G1624G, p.K1637K, p.M1646T, p.S1647T, c.5015+32A>G, c.5170+23T>A, c.5317+32C>T, p.G1819G, c.5948+48C>T, p.N2081D, p.E2108E e c.6381+30A>G). A frequência total de alterações potencialmente patogênicas ou patogênicas detectadas em nossa amostra foi de 3,4% (incluindo a mutação p.G2019S, anteriormente descrita em 2 artigos publicados por nosso grupo: Pimentel et al., 2008; Abdalla-Carvalho et al., 2010), sendo a frequência de mutações nos casos familiares (11,1%) cerca de seis vezes maior do que a encontrada nos casos isolados da DP (1,8%). Os resultados alcançados neste estudo revelam que mutações no gene LRRK2 desempenham um papel significativo como fator genético para o desenvolvimento da DP em pacientes brasileiros.