Disc degenerative changes are directly or indirectly associated with spinal pain and disability. Literature revealed a high prevalence of disc degeneration in the thoracic region, however thoracic MRI degeneration trends and information on disc biochemical matrix constituents are limited for thoracic discs compared to lumbar and cervical discs. The objective of this thesis was to use MRI to investigate the prevalence of disc degenerative changes affecting the human thoracic spine, and to determine the factors affecting spinal disc biochemical matrix. A 3-point subjective MRI grading scale was used to grade the films. The feasibility of using archived formalin-fixed cadaver material was investigated to analyse collagen and elastin crosslinks. The prevalence of degenerative changes in human thoracic discs and vertebrae (T1 to T12) was determined retrospectively from an audit of 216 MRI cases, using sagittal T1- and T2-weighted MR images. In a subsequent series of ex-vivo studies, human thoracic discs and LF from 26 formalin-fixed and two fresh spines, involving all thoracic levels, were examined macroscopically to determine the degeneration status. Subsequently, disc and ligament tissues were analysed biochemically for collagen (pyridinoline and deoxypyridinoline) and elastin (desmosine and isodesmosine) crosslinks. These crosslinks were extracted from hydrolysed samples by cellulose partition chromatography, and analysed by reverse-phase HPLC. Collagen content was determined using its hydroxyproline content, and proteoglycan content was assayed using a modified DMB assay for chondroitin sulphate. Finally the MRI and macroscopic assessments of thoracic discs, were compared with the biochemical data from two fresh cadaver thoracic spines. The 3-point MRI grading scale had a high inter- (k = 0.57 to 0.78) and intra-rater (k = 0.71 to 0.87) reliability. There were no significant differences in the collagen and elastin content and extent of collagen crosslinks between formalin fixed and unfixed ligament and disc tissues, after 25 weeks of formalin fixation. From the in-vivo MRI series of investigations (n = 216 MRI films), the prevalence of thoracic disc degenerative and vertebral morphological changes revealed significant age, gender and spinal level trends (p < 0.05).Generally, males had a higher propensity for disc degeneration in contrast to females, especially older females, where the trend showed a higher prevalence of osteophytes and vertebral body changes. In particular, the mid and lower thoracic levels have a higher prevalence of degenerative changes, except for osteophytes and anterior vertebral wedging. With increased age, there was a concomitant increase in anterior wedging and bi-concavity and disc degenerative changes except for end-plates. The biochemical investigations on the ex-vivo series of formalin-fixed thoracic discs (n = 303) also revealed significant changes in the disc matrix due to degeneration status, age, gender and spinal regional factors. With increased age, normal disc matrices have significantly lower collagen content and extent of pyridinoline (p < 0.001). In contrast, the degenerated disc matrix revealed significantly higher collagen content and extent of deoxypyridinoline (p < 0.05). These findings suggest that an altered matrix existed in normal ageing discs, which render the disc prone to injury and degeneration over the life span. The higher collagen and deoxypyridinoline in degenerated disc matrices reflects an increase in chondrocyte synthesis, and is also a novel finding, suggesting that they may be used as markers of ageing and degeneration processes. The biochemical investigations on another series of ex-vivo spinal LF tissues (n = 364), revealed that this had a lower collagen and pyridinoline, but significantly higher elastin and deoxypyridinoline compared to spinal discs (p < 0.05). Elastin crosslinks however were difficult to detect in spinal discs, being present in negligible amounts in a few lumbar discs. The elastin crosslinks in the LF were not significantly affected by age, but were significantly higher in calcified, and female ligamentum tissues, and also in the lumbar region (p < 0.05). These MRI prevalence findings enhanced our knowledge of vertebral body and disc degeneration trends in the thoracic region and contributed to the interpretation of MR images for pathology in the human thoracic spine. Information on the associated collagenous and elastic changes in the disc and ligamentum matrices provide original data and insight on the pathogenesis of degeneration in the disc matrix from a biochemical perspective, highlighting gender, age and spinal level influences on the matrix tensile strength and cellular synthetic activities.

Dissertation (Ph.D.)--University of South Florida, 2009. / Includes vita. Includes bibliographical references. Also available online.

Today, unlike yesterday we talk about Moral Regeneration amongst the Vhavenḓa youth of today and throughout the whole world. Strategies of combating this monster that is snatching our youth are recommended in this study. The problem dealt with in this study is the issue of Moral degeneration amongst the youth which needs to be regenerated. There are many causes of moral degeneration amongst the youth discussed in this study which are accompanied by the remedial strategies. As a way forward in this study, observations of researchers and scholars on how to find the solution about moral degeneration that has impacted on the lives of Vhavenḓa youth and other youth of today around the globe were focused on. The literature review in this study was based more on issues that are linked to Indigenous Knowledge Systems as discussed by various scholars. This study used the qualitative research methodology though quantitative minimally. The sampling of data was more purposive though there were cases of convenience and snowballing so as to get more data. Data for this research study was collected through questionnaires and interviews from a host of interviewees. This data was analysed using open and axial coding. The findings were grouped or categorised into major themes in terms of selective coding. Reasons behind the findings were explained too. Finally, consequences, implications for further study and also recommendations were indicated. / African Languages / D. Litt. et Phil. (African languages)

A non-experimental quantitative, descriptive and contextual study which sought to examine the level of awareness about Diabetic Retinopathy (DR), and how aware female diabetic patients were about retinal screening as a preventative measure to eye complications and blindness was conducted. The objective of the study was to explore and describe the variables related to the awareness level of female diabetic patients about Diabetic Retinopathy and diabetic retinal screening. A convenient sample of 149 respondents was obtained. A questionnaire was used to collect data. Data was analysed using the Statistical Package for Social Sciences (SPSS), 13.0 computer software program. Results evidenced a good level of awareness about DR. Recommendations based on the findings were made for consideration in clinical practice, education and research. / Health Studies / M.P.H.

Abstract Low back pain (LBP) is a highly prevalent musculoskeletal condition and the leading cause for workplace absenteeism. Lumbar disc degeneration (DD) is considered as a contributing factor to LBP. The role of genetic factors in the development of lumbar DD has been demonstrated to be significant, with heritability estimates ranging from 64% to 81%. Modic change (MC), a distinct phenotype of lumbar DD, is a subchondral and vertebral bone marrow change revealed only by magnetic resonance imaging (MRI). MC has been associated with LBP in both clinical samples and the general population. The genetic background of MC is largely unknown, and the heritability of MC has not previously been assessed. The aim of this study was to assess the heritability of MC using a twin study, identify predisposing genetic factors for MC in a family-based design using whole-exome sequencing and to identify genetic loci associated with MC using genome-wide association study (GWAS) meta-analysis. An additional aim was to study the prevalence, incidence and morphology of MC. The data consisted of two general population samples, the Northern Finland Birth Cohort 1966 (NFBC1966) and TwinsUK from the United Kingdom, as well as two Finnish families from the Oulu region. MC was found to be partly heritable with a heritability estimate of 30%. Two novel candidate genes, HSPG2 and MAML1, were found co-segregating with MC in two Finnish families. Both genes are important in the growth and differentiation of chondrocytes. Finally, a genetic locus on chromosome 9 was found to be significantly associated with MC using genome-wide meta-analysis of NFBC1966 and TwinsUK. These results showed that genetic factors play a role in the development of MC. In conclusion, this thesis increased the knowledge on the genetics of MC. However, the specific roles of these genes need to be studied further. / Tiivistelmä Alaselkäkivun kansaterveydellinen merkitys on suuri, sillä jopa 84% aikuisista kärsii siitä elämänsä aikana. Selkäkivun vuoksi Suomessa kertyy yli 2 miljoona sairauslomapäivää vuodessa. Välilevyrappeumaa pidetään merkittävänä tekijänä alaselkäkivun synnyssä ja perinnölliset tekijät selittävät välilevyrappeuman synnystä jopa 74%. Modic-muutokset ovat selkärangan välilevyjen päätelevyjen ja subkondraalisen luun muutoksia, jotka voidaan havaita ainoastaan magneettikuvauksella. Niitä pidetään välilevyrappeuman alatyyppinä. Modic-muutosten on osoitettu olevan yhteydessä alaselkäkipuun, mutta etiologia tunnetaan huonosti. Perinnöllisyyden osuutta Modic-muutoksien synnyssä ei ole aiemmin tutkittu ja niiden taustalla vaikuttavat geneettiset tekijät ovat pääasiassa tuntemattomia. Tämän tutkimuksen tavoitteena oli arvioida perinnöllisyyden osuutta Modic-muutoksissa kaksoisaineistossa, tunnistaa Modic-muutoksille altistavia geneettisiä muutoksia perheaineistossa käyttäen eksomisekvensointia ja tunnistaa genomin alueita, jotka assosioituvat Modic-muutoksiin. Tutkimus perustui kahteen väestöperäiseen aineistoon: Pohjois-Suomen Syntymäkohorttiin 1966 ja TwinsUK-kaksosaineistoon Yhdistyneistä kuningaskunnista sekä kahteen pohjois-suomalaiseen perheeseen. Tutkimuksessa osoitettiin, että Modic-muutokset ovat perinnöllisiä ja, että perinnölliset tekijät selittävät noin 30% niiden ilmenemisestä. Lisäksi tutkimuksessa tunnistettiin kaksi uutta alttiusgeeniä; HSPG2- ja MAML1-geenit. Molemmilla geeneillä on tärkeä rooli rustosolujen kasvamisessa ja erilaistumisessa. Tutkimuksessa myös tunnistettiin kromosomista 9 genomin alue, joka assosioituu Modic-muutoksiin. Väitöskirjassani osoitettiin, että perinnöllisillä tekijöillä on merkitystä Modic-muutosten synnyssä. Kokonaisuudessaan tämä väitöskirja kasvattaa ymmärrystä Modic-muutoksista, mutta lisätutkimusta aiheesta tarvitaan.

A tese propõem uma metodologia, em nível de pesquisa, por intermédio do desenvolvimento e da adaptação de ferramentas de apoio computadorizado, capaz de realizar a segmentação da imagem dos discos intervertebrais da região lombar da coluna vertebral humana, de maneira semiautomática reduzindo drasticamente o tempo gasto manualmente neste procedimento, sem perder sua acurácia e, ainda, garantindo maior reprodutibilidade em seus resultados. Foram utilizadas imagens sagitais de ressonância magnética ponderadas em T2 de 285 discos intervertebrais de 70 pacientes, classificados segundo o grau de severidade da degeneração discal definido pelo critério proposto por Pfirrmann. A classificação computacional dos discos foi realizada com base em atributos quantitativos extraídos dos histogramas de níveis de cinza e de informações de textura das imagens. O desempenho dos métodos computacionais de segmentação foi avaliado com base no Coeficiente de Jaccard, na distância de Hausdorff e no Erro Médio Quadrático. O desempenho dos métodos computacionais de classificação foi também avaliado com base em medidas similares à aplicação da sensibilidade, da especificidade e da área sob a curva ROC. A segmentação manual e a classificação por inspeção visual dos discos realizadas por três profissionais experientes foram utilizadas como padrão ouro para a comparação. Os principais resultados indicaram a médio de 63,22% para o Coeficiente de Jaccard, as médias de 0,044 das distâncias de Hausdoff e de 0,014 para o EMQ na comparação entre as imagens. Além disso, a segmentação semiautomatizada diferiu em uma taxa média de 30% em relação à segmentação manual e a classificação da degeneração discal, por redes neurais artificiais difere em menos de 2%, ao ser comparada ao procedimento de classificação manual realizado pelos especialistas. / The thesis proposes a methodology at the level of research through the development and adaptation of computerized support tools, able to perform the image segmentation of the intervertebral discs of the lumbar region of the human spine, semiautomatic way dramatically reducing time spent manually in this procedure, without losing its accuracy and also ensuring more reproducible in their results. Were used sagittal MRI T2- weighted of 285 intervertebral discs from 70 patients, classified according to the severity of disc degeneration defined by the criteria proposed by Pfirrmann. The computational classification of disks was based on quantitative attributes extracted from histograms of gray level images and the texture information. The performance of computational segmentation methods was evaluated based on Jaccard coefficient, Hausdorff distance and Mean Square Error. The performance of the computational classification methods was evaluated based on measures of sensitivity, specificity and the area under the ROC curve. The manual segmentation and visual inspection classification of the discs made by three experienced professionals were used as the gold standard for comparison. The main results showed an average Jaccard coefficient of 63.22%, the average Hausdoff of distances was 0.044 and 0.014 Mean Square Error average when comparing the images from both segmentation targets. Additionally, the targeting semiautomatic differed by an average of 30% compared with manual segmentation and classification of disc degeneration provided from an artificial neural networks differs by less than 2% when compared to manual sorting procedure performed by experts.

INTRODUÇÃO: A reparação das lesões de nervos periféricos com perda extensa de substância, onde a sutura direta não é viável, ainda apresenta nos dias atuais resultados variáveis e dependentes de diversos fatores. O tratamento mais comumente utilizado nestes casos é a auto-enxertia de nervos, com sacrifício de um nervo de outra região do corpo, procedimento que, entretanto, pode trazer algumas dificuldades e consequências. Desta forma, a busca por novas técnicas, como a possibilidade de utilização de nervos preservados em baixas temperaturas, representa um avanço inestimável no campo da reparação de lesões nervosas. OBJETIVO: O objetivo deste estudo foi realizar avaliações funcionais, eletrofisiológicas e histomorfométricas que permitam comparar a regeneração nervosa autógena em enxerto convencional versus enxerto preservado a frio, em modelo experimental de ratos, após denervação a fresco ou conservação de um segmento do nervo em baixa temperatura por 14 dias e por 50 dias. MÉTODOS: Foram utilizados 20 ratos Wistar de peso e idades aproximadamente iguais, divididos em quatro grupos de cinco animais. Os grupos 1 e 3 serviram de controle respectivamente para os grupos 2 e 4, utilizando enxertia de nervo convencional por 14 dias (grupo 1) e por 50 dias (grupo 3). O grupo 2 utilizou enxertia de nervo preservado a 4 graus Celsius em solução Celsior® por 14 dias, enquanto o grupo 4 foi submetido à preservação a frio na mesma solução por 50 dias. Foram realizadas análises funcionais da marcha, análises de potenciais evocados e análises histomorfométricas dos animais em diversos momentos. As análises funcionais utilizaram uma aparelhagem própria para estudo da marcha em pequenos animais de experimentação, denominada catWalk®, que fornece medidas estáticas e dinâmicas da marcha, com parâmetros como a pressão em relação à pata contralateral e a área máxima da impressão plantar do animal, tendo sido captados os dados antes do procedimento de retirada do enxerto e após a realização da enxertia, neste último caso com avaliações quinzenais até que tenham sido completados 60 dias de pós- operatório. As análises de potenciais evocados motores analisaram a latência e a amplitude dos estímulos nervosos e foram realizadas 60 dias após os procedimentos de enxertia. As análises microscópicas observaram a contagem de axônios mielinizados e a área destas fibras nervosas nas regiões proximal e distal aos reparos, aos 60 dias após os procedimentos, comparando também as relações entre a região distal e proximal de cada um destes parâmetros através dos índices de regeneração e mudança de área. RESULTADOS: A enxertia com nervo preservado a frio por 14 dias apresentou resultado funcional semelhante ao seu grupo controle na análise da área máxima de contato e da pressão máxima de contato da pata operada em todas as avaliações. Já a conservação do enxerto a frio por 50 dias resultou em superioridade funcional em todos as avaliações em relação a seu grupo controle. Os estudos eletrofisiológicos mostraram cada grupo de enxertia preservada a frio com resultados similares a seu grupo controle, tanto em relação à latência, quanto à amplitude nos dois músculos avaliados. As análises histomorfométricas resultaram em índices de regeneração e de mudança de área semelhantes na comparação entre os grupos 60 dias após os procedimentos de enxertia. CONCLUSÕES: A conservação a frio do enxerto de nervo durante 14 dias e durante 50 dias apresentou resultados funcionais da regeneração iguais ou superiores aos enxertos convencionais e resultados eletrofisiológicos e histológicos semelhantes aos respectivos grupos controle de enxertos convencionais, demonstrando um futuro promissor para a utilização clínica de enxertos preservados a frio em um \"banco de nervos\" / INTRODUCTION: The repair of peripheral nerve injuries with extensive loss of substance, where direct suture is not feasible, at the present time still has variable results and dependence on many factors. The treatment most commonly used in these cases is the nerve autograft, with sacrifice of a nerve from another region of the body. This procedure, however, can sometimes lead to some difficulties and consequences. Therefore, the search for new techniques such as the possibility of using cold preserved nerves, is a great advancement in the field of repairing nerve damage. OBJECTIVE: The purpose of this study was to perform functional, electrophysiological and histomorphometric evaluations to compare conventional autografts versus cold-preserved autografts of the sciatic nerves of rats, after fresh denervation or conservation of a nerve segment at low temperature for 14 days and 50 days. METHODS: 20 Wistar rats of approximately equal ages and weight were divided into 4 groups of 5 animals. Groups 1 and 3 were treated with a conventional nerve graft after denervation for 14 days and 50 days, respectively; they served as controls for groups 2 and 4, which were treated with cold-preserved nerve grafts immersed in a Celsior® solution at 4 degrees Celsius for 14 and 50 days, respectively. Functional gait analysis, evoked potential analysis and histomorphometric analysis of the animals were performed at different times. Functional analysis used equipment for gait study in small animal experiments, called catWalk®, which provides static and dynamic measurements, with parameters such as pressure relative to contralateral paw and the maximum area of the footprint of the animal, and these data were captured before the graft withdrawal procedure and after grafting, in this latter case the functional analysis was made every 15 days until they had been completed 60 days after surgery. The motor evoked potential analysis examined the latency and amplitude of nerve stimuli and was made 60 days after the grafting procedures. The microscopic analysis measured myelinated axons and the area of these nerve fibers in the proximal and distal regions to the repair sites at the end of 60 days after the procedures, also comparing the relationship between the distal and proximal regions of each of these parameters through the regeneration and area change rates. RESULTS: Cold preservation of nerve graft for 14 days showed functional results similar to those of its control group for the maximum contact area and for the maximum pressure intensity of the operated paw in all evaluations. Cold preservation of nerve graft for 50 days resulted in functional superiority in all assessments compared with its control group. Cold preservation of nerve graft for 14 days and 50 days showed electrophysiological results similar to those of their respective control groups, both in terms of latency, as to the amplitude in the two muscles evaluated. Histomorphometric analysis showed similar regeneration and area change rates for all the groups 60 days after the grafting procedures. CONCLUSIONS: The cold preservation of nerve grafts for 14 days and 50 days showed similar or superior functional results and similar electrophysiological and histological results compared with their respective conventional graft control groups, indicating a promising future for the clinical utilization of cold preserved grafts in a \"nerve bank\"

Les yeux forment des avant-postes visuels importants du cerveau. Comme les autres organes, la rétine sensorielle des yeux est vulnérable aux effets nocifs des facteurs environnementaux, tels que la lumière et l'oxygène. Dans ce travail, nous nous sommes concentrés sur l’impact de l’exposition à une lumière constante et l’hyperoxie prolongée sur l'architecture et la fonction rétinienne. Dans la première partie de notre étude, nous avons montré qu’ une exposition de sept jours à une lumière constante perturbe la phagocytose des bâtonnets et cônes et régule négativement leur renouvellement dans la « rétine riche en cônes " d’Arvicanthis ansorgei. Notre étude donne un aperçu sur la physiopathologie des cônes, ce qui représente la principale source de handicap visuel dans une variété de pathologies rétiniennes, y compris la rétinite pigmentaire (RP) et la dégénérescence maculaire liée à l'âge (DMLA). Dans la deuxième partie de notre étude, nous avons montré qu’ une exposition de cinq jours à l’hyperoxie entraîne chez les souris néonatales une perte significative de cellules ganglionnaires dans les régions périphériques de la rétine, et de cellules à mélanopsine (ipRGC). L’exposition prolongée à l’hyperoxie perturbe également la capacité de photoentrainment des animaux probablement due à la perte des ipRGC et la perte de la rhodopsine dans les segments externes des bâtonnets chez les animaux traités. / Eyes form important visual outposts of the brain. Just like other organs, sensory retina in the eyes is also vulnerable to the injurious effects of environmental factors; such as light and oxygen. In this work, we have focused on the impacts of constant prolonged light and hyperoxia on the retinal architecture and function. In the first part of our study, we show that seven days of constant light disrupts rod and cone phagocytosis and downregulates their turnover in the “cone rich retina” of Arvicanthis ansorgei. The study gives an insight on the cone pathophysiology, which represents the major source of visual handicap in a variety of retinal pathologies, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In the second part of our study, we show that five days of hyperoxia treatment in the neonatal mice results in the significant loss of retinal ganglion cells in the peripheral regions; the loss of melanopsin expressing retinal ganglion cells (ipRGC) was found to be significant. Hyperoxia also affects the photoentrainment capability of the animals probably because of the loss of ipRGC and the loss of rhodopsin in the outer segments of the photoreceptors in the treated animals.

A Doença Reumática Cardíaca (DRC) é uma séria complicação de orofaringite causada por determinados sorotipos de Streptococcus pyogenes não tratada adequadamente em indivíduos suscetíveis. É um grande problema de saúde pública, principalmente nos países não desenvolvidos e em desenvolvimento, como Brasil, Índia, países da África, regiões de população aborígine da Austrália, e Egito. É altamente debilitante e com alta taxa de mortalidade devido ao comprometimento cardíaco. As lesões miocárdicas iniciais regridem, mas as lesões valvares, principalmente a mitral e a aórtica, são irreversíveis e progressivas. Muitos estudos já caracterizaram a resposta imune celular (linfócitos T) e humoral nos indivíduos acometidos pela doença. Mimetismo molecular e espalhamento de epítopo são os principais mecanismos que se pensa estar envolvidos na patogênese da DRC. Avaliamos, nesta pesquisa, o perfil de expressão proteica em valvas mitrais de indivíduos acometidos por DRC. Para detectar alterações específicas desta doença, comparamos as expressões de proteínas nos grupos portadores de DRC com insuficiência (DRC-INS) e com estenose (DRC-EST) a um grupo de indivíduos com degeneração mixomatosa de valva mitral (DMX) e outro sem valvulopatias (CTL). Alterações especificamente observadas em tecido mitral na DRC-INS ou DRC-EST em fases avançadas da doença podem explicar o mecanismo de desenvolvimento desses dois tipos de lesão. Foram encontradas 25 \"spots\", correpondendo a 29 proteínas diferencialmente expressas nos grupos com valvulopatias, refletindo principalmente alterações na matriz extracelular. Encontramos importante clivagem diferencial da vimentina, cuja proteína íntegra possui 54 kDa, formando fragmentos com ~40 e ~45 kDa, aumentados na DRC, principalmente na DRC-INS. O colágeno do tipo VI, com aproximadamente 95 kDa, encontrou-se com expressão diminuída exclusivamente no grupo DRC-INS. A Vitronectina foi encontrou-se aumentada em na DMX e na DRC-EST, em relação ao grupo controle, principalmente na DRC-EST. Lumican, por sua vez, teve expressão diminuída na DMX e na DRC-EST, apesar de possuir um único \"spot\" com expressão aumentada na DRC. Utilizando métodos de análise de padrões de expressão protéica in silico foram identificados conjuntos de proteínas capazes de discriminar as amostras de valva mitral por etiologia da doença. O presente trabalho pode auxiliar na elucidação dos mecanismos de desenvolvimento da doença e de alterações estruturais do tecido mitral em resposta às lesões autoimunes, bem como no diagnósticoda DRC. / Rheumatic Heart Disease (RHD) is a serious complication of oropharingitis caused by some serotypes of Streptococcus pyogenes not properly treated in susceptible individuals. It is a public health concern, mainly for undeveloped and developing countries, such as Brazil, India, some countries in Africa, aboriginal regions in Australia, and Egypt. It is highly debilitating with a high mortality rate due to cardiac commitment. Initial myocardial lesions disappear, but valvar lesions, mainly mitral and aortic, are irreversible and progressive. Many studies have characterized cellular (T lymphocytes) and humoral responses in individuals affected by the disease. Molecular mimicry and epitope spreading are the main mechanisms thought to be involved in the pathogenesis of RHD. We evaluated, in this research, the profile of protein expression in mitral valves from individuals affected by RHD. To detect alterations specific of this disease, we compared protein expression in the group of RHD with regurgitation (RHD-RGT) and stenosis (RHD-STN) to a group of individuals with mitral valve myxomatous degeneration (MXD) and another group without valvulopathies (CTL). Alterations specifically observed in the mitral tissue of RHD-RGT and RHD-STN in advanced stages of the disease can explain the mechanism of development for these two kinds of lesions. Twenty-five spots, corresponding to 29 proteins were found to be differentially expressed in the valvulopathy groups, reflecting mainly alterations in extracellular matrix. We found important differential cleavage of vimentin, the whole protein having 54 kDa, in fragments with ~40 and ~45 kDa, increased in RHD, mainly in RHD-RGT. Collagen type-VI, with approximatelly 95 kDa, was found to have decreased expression exclusivelly in the RHD-RGT group. Increased expression of Vitronectin was detected in DMX and RHD-EST groups, compared to the CTL group, mainly in the RHD-STN. Lumican, in turn, had decreased expression in the MXD and RHD-STN groups. By using in silico methods for analysis of patterns of protein expression, we identified sets of proteins capable of discriminating mitral valve samples by disease etiology. The present study might help elucidating the mechanisms of disease development and structural alterations in the mitral tissue in response to the autoimmune lesions, as well as in the diagnosis of RHD.

Atualmente, as demências tornam-se mais prevalentes e constituem-se como um importante problema de saúde pública mundial. A Degeneração Lobar Frontotemporal (DLFT) e a Doença de Alzheimer (DA) são as de maior incidência. A investigação dos fatores de risco para as demências degenerativas inscreve-se entre os temas mais relevantes das neurociências e a avaliação dos fatores de risco de natureza genética tem produzido contribuições importantes. Na DLFT, mutações no gene TARDBP, codificador da proteína nuclear TDP-43, estão entre as ocorrências genéticas mais descritas, enquanto que para a DA, o alelo 4 do gene da apolipoproteína E (APOE) é o principal fator de risco. Pacientes com diagnóstico clínico de DLFT (n=47) e de DA provável (n=30) recebidos do ambulatório do Grupo de Neurologia Cognitiva e do Comportamento (GNCC) da Clínica Neurológica do HC-FMUSP foram convidados a participar do estudo. Amostras de sangue foram coletadas para a realização da extração de DNA linfocitário. Os éxons de 1-6 do gene TARDBP foram amplificados por PCR e seus produtos foram sequenciados em sequenciador automático. Os polimorfismos do gene APOE foram determinados através da técnica de PCR em tempo real. A análise do gene da TDP-43 em pacientes com DLFT mostrou a presença de uma mutação na região do éxon 6 do TARDBP (g.14935A>G) em um paciente do sexo masculino, com idade de 54 anos e diagnóstico de demência semântica. Na genotipagem dos pacientes de DA, foi observado que a metodologia utilizada, através de PCR em tempo real mostrou-se eficiente em detectar os polimorfismos do gene APOE, fornecendo resultados compatíveis quando comparados aos demais estudos brasileiros publicados anteriormente / Brazil is one of the developing countries that are undergoing a process of demographic transition in which the elderly represents a significant proportion of the total population. Neurodegenerative illnesses most commonly appear at such ages. Frontotemporal lobar degeneration (FTLD) and Alzheimers disease (AD) are the most frequent causes for dementia. The investigation of risk factors for degenerative dementia is a relevant subject of neurosciences and the evaluation of the nature of genetic risk factors has produced the most important contributions. Mutations in TARDBP gene, the encoder of the TDP-43 nuclear protein, appear as the most frequent genetic occurrences for FTLD, whereas, in DA, the 4 allele of the apolipoprotein E (APOE) is the major genetic risk factor. Patients with clinical diagnosis of FTLD types of families and sporadic (n=47) and probable AD (n=30) from the ambulatory of Cognitive Neurology Group and Behavior (CNGB) of Neurological Clinic of HC-FMUSP were invited to participate in this study. Blood samples were collected for lymphocytic DNA extraction. The APOE gene polymorphisms are being determined through the real time PCR technique. The 1-6 exons of TARDBP gene were amplified by PCR and their products were sequenced in automated sequencer. The TDP-43 gene analysis in patients with FTLD showed the presence of one mutation in the region of exon 6 TARDBP gene in a male patient of 54 years old, with diagnoses of semantic dementia. Regarding DA patients genotyping, the real time methodology has been shown as an efficient approach to detect APOE polymorphisms, presenting data similar to those observed in other Brazilian studies