PRMT biology during skeletal muscle disuse. / Protein arginine methyltransferase 1 (PRMT1), PRMT4 (also known as co-activator-associated arginine methyltransferase 1; CARM1), and PRMT5 are critical components of a diverse set of intracellular functions. Despite the limited number of studies in skeletal muscle, evidence strongly suggests that these enzymes are important players in the regulation of phenotypic plasticity. However, their role in disuse-induced muscle remodelling is unknown. Thus, we sought to determine whether denervation-induced muscle disuse alters PRMT expression and activity in skeletal muscle within the context of early signaling events that precede muscle atrophy. Mice were subjected to 6, 12, 24, 72, or 168 hours of unilateral hindlimb denervation. The contralateral limb served as an internal control. Muscle mass decreased by ~30% following 168 hours of disuse. Prior to atrophy, the expression of muscle RING finger 1 and muscle atrophy F-box were significantly elevated. The expression and activities of PRMT1, CARM1, and PRMT5 displayed differential responses to muscle disuse. Peroxisome proliferator-activated receptor-γ coactivator-1α, AMP-activated protein kinase (AMPK), and p38 mitogen-activated protein kinase expression and activation were altered as early as 6 hours after denervation, suggesting that adaptations in these molecules are among the earliest signals that precede atrophy. AMPK activation also predicted changes in PRMT expression and function following disuse. Our study indicates that PRMTs are important for the mechanisms that precede, and initiate muscle remodelling in response to neurogenic disuse. / Thesis / Master of Science (MSc) / Skeletal muscle is a plastic tissue that is capable of adapting to various physiological demands. Previous work suggests that protein arginine methyltransferases (PRMTs) are important players in the regulation of skeletal muscle remodelling. However, their role in disuse-induced muscle plasticity is unknown. Therefore, the purpose of this study was to investigate the role of PRMTs within the context of early, upstream signaling pathways that mediate disuse-evoked muscle remodelling. We found differential responses of the PRMTs to muscle denervation, suggesting a unique sensitivity to, or regulation by, potential upstream signaling pathways. AMP-activated protein kinase (AMPK) was among the molecules that experienced a rapid change in activity following disuse. These alterations in AMPK predicted many of the modifications in PRMT biology during inactivity, suggesting that PRMTs factor into the molecular mechanisms that precede neurogenic muscle atrophy. This study expands our understanding of the role of PRMTs in regulating skeletal muscle plasticity.

Recent recommendations are that older adults increase their dietary protein intake to intakes higher than are currently recommended to mitigate sarcopenia-induced muscle loss caused in part by anabolic resistance. Protein supplementation may serve as an effective strategy to meet protein intake goals; however, protein supplements vary in their quality, which may impact muscle protein turnover. Protein quality is determined by the digestibility and content of essential amino acids in a protein source and may play an important role in mitigating the loss of muscle mass and muscle protein synthesis (MPS) during energy restriction (ER), acute reductions in physical activity, which we modeled using enforced step reduction (SR), and during recovery from SR. We aimed to determine whether the quality of a protein supplement – whey protein (higher quality) versus collagen peptides (lower quality) – would impact the reduction in fat-free bone-free mass (FBFM) and MPS (Study 1), and also to compare differences in functional variables: strength loss in men and women, and single fibre function with SR in men (Study 2). In Studies 1 and 2 we compared supplementation with whey protein (WP) and collagen peptides (CP), higher and lower quality proteins respectively, as part of a higher protein diet provided to older adults during one week of ER (-500 kcal/d), two weeks of step reduction (< 750 steps/d) (ER+SR) and one week of recovery (RC). Two weeks of ER+SR significantly reduced FBFM in both the WP and CP groups with greater FBFM recovery with WP. MPS was significantly reduced following ER in both groups and did not decrease further during ER+SR. MPS was increased above ER+SR following 1 week of RC in the WP group only. ER+SR significantly reduced maximum voluntary contraction (MVC) in both men and women; however, following RC men fully recovered their strength and women did not. In Study 3, we aimed to determine the impact of WP and CP supplementation combined with unilateral resistance exercise (RE) to augment the acute and longer term MPS response in healthy older women. Acutely, rates of MPS were elevated following WP+RE and with WP alone while MPS was elevated only in CP+RE. Six days of supplementation increased MPS in WP and WP+RE with no increase in MPS with CP or CP+RE. Collectively, these studies demonstrate that protein quality is an important variable to consider in selecting a protein supplement for older adults and for recovering from inactivity. / Thesis / Doctor of Science (PhD) / At the end of the 5th decade of life, adults will have lost an appreciable amount of muscle mass and strength versus what they had in their 3rd decade of life. This age-related loss of muscle mass and strength is known as sarcopenia. Additionally, as they age, adults will experience brief periods of reduced physical activity due to illness, injury, or recovery from surgery. Such periods are associated with a rapid loss of muscle and strength creating a brief period of ‘accelerated sarcopenia’. Strategies to combat the loss of muscle and strength in these periods include increasing protein intake and even periodic exercise which may help to reduce the negative impact of physical inactivity. In particular, higher quality protein sources (protein derived from animal sources or soy) and weightlifting may better help muscles recover from inactivity. Our main findings were that consuming high quality protein (whey protein) stimulated the process of muscle building that is normally reduced with inactivity. Importantly, when combined with resistance exercise, we were able to increase the rate at which healthy older women built muscle with whey protein in comparison to a lower quality protein source (collagen peptides). These findings provide novel and insightful information for the recommendations of protein supplement types to older adults to increase daily protein intake to preserve muscle mass with age.

No description available.

L’hypodynamie-hypokinésie est une situation correspondant à une diminution de l’activité motrice (hypokinésie) couplée à une diminution des charges corporelles (hypodynamie). Chez l’homme, cette situation est retrouvée lors d’une immobilisation, d’un alitement prolongé, d'un séjour en microgravité, ou lors du vieillissement (syndrome d’immobilité). L’hypodynamie-hypokinésie entraine une sévère altération de la performance motrice, notamment de l’équilibre, de la posture et de la locomotion. Cette altération est due à une dégradation du système musculaire (atrophie, changements phénotypiques), mais également à une modification des propriétés fonctionnelles du cortex sensorimoteur (réorganisation corticale, changements d’excitabilité corticale, modifications morphologiques). Si l’altération du système musculaire est bien décrite dans la littérature, les mécanismes impliqués dans la plasticité corticale restent mal connus. Une meilleure compréhension des systèmes mis en jeu dans l’hypodynamie-hypokinésie permettrait de développer des stratégies de prévention et/ou de récupération chez les patients soumis à cette situation. Dans cette optique, un modèle animal est communément utilisé au laboratoire. Il s'agit du modèle d'élévation du train postérieur pendant 14 jours chez le rat. Ainsi, les charges corporelles, s’exerçant habituellement sur les membres postérieurs, sont prévenues et l’activité musculaire limitée. Ce modèle animal reproduit la plupart des effets de l'hypodynamie-hypokinésie décrits chez l'homme.L’objectif de cette étude a été d’explorer les mécanismes de la réorganisation corticale induite par l’hypodynamie-hypokinésie. Notre intérêt s’est plus particulièrement porté sur l’insulin-like growth factor 1 (IGF-1), une protéine ubiquitaire possédant de nombreux rôles au niveau cérébral. En effet, en se fixant à son récepteur, l’IGF-1, parmi une multitude de phénomènes, stimule l’angiogenèse, la neurogenèse, et participe à la plasticité synaptique. De plus, il est reconnu comme étant un acteur central des effets bénéfiques de l’exercice physique au niveau cérébral.Aussi, dans un premier temps, nous avons déterminé les effets de cette hypoactivité sur l’IGF-1 et les voies de signalisation associées dans plusieurs structures impliquées dans la régulation de la performance motrice (cortex sensorimoteur, striatum, cervelet). Nos résultats montrent une sévère diminution des taux d’IGF-1 et de l’activation de la voie PI3K-AKT, et ce spécifiquement dans le cortex sensorimoteur.Dans un second temps, nous avons voulu déterminer si en maintenant le taux d’IGF-1 pendant toute la durée de l’hypodynamie-hypokinésie, il était possible de prévenir la réorganisation corticale et ses conséquences délétères sur le comportement moteur. Pour cela, dans une première partie, notre étude a porté sur le cortex somesthésique et la sensibilité tactile. Nos résultats montrent que l’IGF-1 prévient partiellement la réorganisation corticale et l’altération de la sensibilité tactile induites par l’hypoactivité. Dans une seconde partie, nous nous sommes intéressés à l’analyse du cortex moteur et de la performance motrice. Il apparait qu’un maintien des taux d’IGF-1 prévient une partie de l’altération du système moteur retrouvée en situation d’hypodynamie hypokinésie. Ainsi, l’ensemble de ces données suggère que la diminution des taux d’IGF-1 observée en condition d’hypoactivité joue un rôle clé dans la réorganisation corticale. De plus, notre étude montre qu’une prévention, même partielle, de cette réorganisation corticale peut induire une amélioration fonctionnelle de la performance motrice. / Hypodynamia-hypokinesia is a condition in which the motor activity (hypodynamia) as well as the weight exerted on the lower limbs (hypokinesia) are reduced. In humans, this condition is induced in immobilization, bed-rest, spaceflight or ageing (immobility syndrome) and is characterized by a chronic reduction in neuromuscular activity. This hypoactivity results in a profound alteration of motor task performances, in particular posture, gait and locomotion. These impairments are due to alterations in the muscular system (atrophy, phenotypic changes), but also to plastic changes in neural functions (cortical reorganization, alterations in cortical excitability, morphologic modifications). While degradation of the muscular system is described in the literature, the mechanisms involved in cortical plasticity are still unclear. A better understanding of the systems involved in hypodynamia-hypokinesia would allow the development of preventive and / or recovery strategies for patients affected by this hypoactivity. In this regard, hindlimb unloading is a disuse rodent model in which the elevation of the hindlimbs, during 14 days, prevents the weight to be normally exerted on the hindlimbs and reduces the normal muscular activity, finally causing hypoactivity. Studies performed on this model have shown that hindlimb unloading and human hypoactivity have similar effects. Today, our interest is turned towards insulin-like growth factor 1 (IGF-1), a ubiquitous protein involved in many cerebral functions. Indeed, IGF-1 is known to improve, inter alia, angiogenesis, neurogenesis and to be involved in synaptic plasticity in the whole brain. Moreover, several publications suggest that IGF-1 might mediate the beneficial effects of exercise on the brain.The aim of this study is to characterize the role of IGF-1 in cortical reorganization induced by hindlimb unloading as well as its functional consequences on motor performance. In the first part of the study, we have determined the effects of hindlimb unloading on IGF-1 level and the impact of its downstream main molecular pathways in motor control (sensorimotor cortex, striatum, cerebellum). Our results indicate that hindlimb unloading induces a decrease in IGF-1 level specifically in the sensorimotor cortex. This alteration is associated to a decrease in activation of the PI3K-AKT pathway. The second part of this study is dedicated to the effects of a restoration of IGF-1 levels, during the whole unloading period, on cortical reorganization and behavioral alterations focusing on sensory cortex and tactile sensory discrimination as well as motor cortex and motor performances. Our results show that treatment with IGF-1 partially prevents cortical reorganization and degradation of tactile sensory discrimination. Additionally, it appears that restoration IGF-1 levels prevent some of the effects of hindlimb unloading on the motor system.Taken together, ours results suggest that the decrease in the level of IGF-1 in the sensorimotor cortex during hindlimb unloading plays a key role in the cortical reorganization induced by hypoactivity. Moreover, our study shows that the prevention of this cortical reorganization, even when partial, can induce functional improvement in motor performance.

Submitted by Geyciane Santos (geyciane_thamires@hotmail.com) on 2015-05-20T15:39:38Z No. of bitstreams: 1 Dissertação - Orlando Gonçalves Barbosa.pdf: 3485435 bytes, checksum: f999ffbbbb167e91874c989cf5564815 (MD5) / Made available in DSpace on 2015-05-20T15:39:38Z (GMT). No. of bitstreams: 1 Dissertação - Orlando Gonçalves Barbosa.pdf: 3485435 bytes, checksum: f999ffbbbb167e91874c989cf5564815 (MD5) Previous issue date: 2014-05-21 / FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas / Religious experience is presented by several researchers as a process of overcoming suffering, disease, disuse drug and other hardships factor. This research had as its central objective to understand the relationship of religious experience with overcoming drug withdrawal, according to users graduates from an institution of care (care) to drug addicts in the city of Manaus. From this, we constructed two articles, the first aimed at understanding how people who used drugs began to conceive of their relationship with the substance in focus and what were the effects of that use on their systems of belonging. The second article was to understand how religious experience is located in the path of a group of people who have overcome drug use after the passage of these for a therapeutic community and the repercussions of this disuse in their systems of belonging. Survey participants were inmates of a therapeutic community (Fazenda da Esperança, Manaus-AM) that were in disrepair for at least one year at the time of the survey. Method was used as a qualitative exploratory approach, adopting categories of systems theory to the analysis of the data, these collected through semi-structured interviews. The results point to the fact that the use and disuse of drugs and suffering related to them are tied to the user, systems and subsystems of belonging, especially to family, work, relationship with peers and religious experience ; Addiction and a ratio of responsibility that positively or negatively feeds back the ratio of use over time. Religious experience is identified as psychosocial process of organizing an identity which integrates sense of transcendence, and shall support new modes of relatedness between individuals and their social networks, in particular the family, community and religious institutions belonging. Recursion and the unpredictability present in the trajectories of use and disuse were also identified as factors that pushed the system to search for homeostasis and thus to overcome. / A experiência religiosa é apresentada por vários pesquisadores como fator de superação de processos de sofrimento, de adoecimento, de desuso de droga e outras adversidades. Esta pesquisa teve como objetivo central compreender a relação da experiência religiosa com a superação do uso de droga, segundo usuários egressos de uma instituição de atendimento (atenção) a dependentes químicos na cidade de Manaus. A partir deste, construiu-se dois artigos, sendo o primeiro voltado à compreensão de como as pessoas que fizeram uso de droga passaram a conceber a relação deles com a substância em foco e quais foram as repercussões desse uso em seus sistemas de pertença. O segundo artigo buscou compreender como a experiência religiosa é situada na trajetória de um grupo de pessoas que superaram o uso de drogas após a passagem destas por uma comunidade terapêutica e as repercussões desse desuso em seus sistemas de pertença. Os participantes da pesquisa foram internos de uma comunidade terapêutica (Fazenda da Esperança, Manaus-AM) que se encontravam em desuso há pelo menos um ano, na ocasião da pesquisa. Utilizou-se como método a abordagem exploratória qualitativa, adotando categorias da teoria sistêmica para a análise dos dados, estes coletados por meio da entrevista semiestruturada. Os resultados encontrados apontam para o fato deque o uso e o desuso das drogas, bem como o sofrimento a elas relacionado estão vinculados ao usuário, seus sistemas e subsistemas de pertença, em especial àfamília, trabalho, relação com os pares e vivência religiosa;numa relação de codependência e corresponsabilidade que retroalimenta positiva ou negativamente a relação de uso, ao longo do tempo. A experiência religiosa é apontada como processo psicossocial organizador de uma identidade a qual integra sentidos de transcendência, e passa a sustentar novos modos de vinculação entre os sujeitos e suas redes sociais, em especial a família, a comunidade e as instituições religiosas de pertença. A recursividade e a imprevisibilidade presentes nas trajetórias de uso e desuso foram identificadas também como fatores que impulsionaram o sistema à busca de homeostasee, portanto, de superação.

Mechanical unloading has deleterious effects on the musculoskeletal system and results in significant reductions in bone density, mass, and strength, which do not fully recover even years after returning to weightbearing. For example, the rate of bone loss in microgravity is 10-fold more rapid than the rate of loss seen in elderly Caucasian females, the population group most predisposed to osteoporosis. This raises concern with individuals who are exposed to multiple bed rest periods or crewmembers who make repeated missions. Exercise offers a way to reduce or reverse these effects. Dual-energy X-ray absorptiometry (DXA) densitometry and bone mineral density (BMD) alone are generally insufficient for capturing the complex changes in bone mass, structure, and integrity and not an accurate predictor of fracture risk. Therefore, it is essential to measure the mechanical properties of bone tissue directly using animal models. The hindlimb unloaded (HU) rat model is a well-established ground-based analog for studying bone response to disuse and effects of spaceflight. The current study is one of the very few that has measured longitudinally densitometric and mechanical properties of bone after repeated simulated microgravity and long-term recovery at multiple anatomic sites in skeletally mature rats. The specific aims were to characterize 1) loss and recovery dynamics of bone following a period of unloading, 2) bone response after a second exposure to 28 days of HU, following an initial 28 days of HU and a recovery period equal to twice the duration of initial exposure, and 3) effects of resistance exercise during recovery period following an initial HU exposure and its effects on a subsequent exposure. In general, our data showed that bone response to unloading and recovery is site-specific. More specifically, we found that: 1) the rat proximal tibia metaphysis modeled the loss and discordant recovery dynamics as seen in the International Space Station (ISS) crewmembers proximal femur better than the rat femoral neck; 2) the initial exposure to HU has minimal effect on the subsequent HU exposure, and detrimental effects of the second HU exposure were milder than the initial due to reduced mechanosensitivity of the bone; 3) exercise significantly enhanced recovery following the initial HU exposure, and losses during the second exposure were not affected by exercise in most cases.

No / This paper provides the results of re-evaluation of a young adult individual from the Romano-British cemetery of 76 Kingsholm, Gloucester with club foot defomity by (Roberts et al 2004). Our reanalysis revealed an extensive bilateral asymmetry involving the lower and upper limb, spine and cranium and a right scoliosis, indicating more than the lower limb was affected. Consideration of the position and shape of the articulated club foot indicated a positional rather than a developmental condition, probably due to unilateral paralysis. Differential diagnosis considered congenital and acquired neuromuscular conditions; we argue that poliomyelitis is the most likely cause. Poliomyelitis is secondary to the infection with poliovirus that can affect the motor neurons from the spinal cord, causing a flaccid paralysis without sensory affection. Because the virus affects individual nerves, the paralysis is muscle-specific causing muscle imbalances and poor posture which can result in deformities and muscle disuse atrophy. Shortening of the leg is the most characteristic sign, however other typical deformations are in the lower limbs are external rotation of the knee, knee hyperestension, ankle and foot deformities (all observed in K131). The evaluation of K131’s entheses and bone structure suggests that, in life, this individual showed physical deformities consisting of a possibly visible atrophy of the left arm and leg, asymmetric gait, clubfoot and slight scoliosis which would have affected not only his appearance but also his ability to move and perform certain tasks. K131’s burial treatment is entirely normative for the period and the wider cemetery context. This could suggest that despite their impairment, this individual was not necessarily marginalised within their social context. However, historical sources account for extensive marginalisation and cruel treatment of the disabled and deformed in this period. So, whilst K131 was buried in a normative manner, it is difficult to reach definitive conclusions regarding how this individual was treated by their contemporaries.

Low trauma hip fractures, due to bone fragility, are a major healthcare burden with serious consequences for individuals in terms of long-term morbidity and mortality; and also for society due to the high medical and care costs associated with these injuries. Because of the association with low bone mass, these fractures are particularly prevalent in elderly populations and are likely to become more common as longevity increases globally. Avoidance of these fractures is therefore an extremely important goal. Low bone mass, manifested in the conditions of osteopenia and osteoporosis, is the primary cause of bone fragility, and reductions in bone mass are the inevitable corollary of aging and menopause. Bone loss may be exacerbated by immobilisation and reduced weight-bearing activity, giving rise to the condition of disuse osteopenia. Immobilisation may itself be the result of low trauma leg fragility fractures that potentially causes further bone density loss. If this loss occurs at the hip, there is an increased risk for hip fracture as a sequela to the original injury. Osteoarthritis is also a condition strongly associated with aging that may necessitate knee arthroplasty as a last stage treatment, potentially causing a period of reduced mobility and weight-bearing activity following surgery. Leg fracture and knee replacement both present additional risk factors for hip fracture due to changes in muscle mass, gait and postural stability that may increase the risk of falls. This study aims primarily to investigate the effects of immobilisation on leg fracture and knee replacement patients, immediately following injury or surgery, in order to quantify bone and muscle loss and to monitor recovery over a one year period. A postmenopausal population were studied as they are already losing bone density systemically and may be at greater risk of further bone loss following immobilisation. Factors of activity, function, weight-bearing, pain, treatments, therapies, health perceptions and mental wellbeing, that potentially contribute to bone loss and recovery, were also investigated. Results from the study may provide information relating to increased future hip fracture risk and lead to treatment options to alleviate bone loss in these groups.

O objetivo geral desta tese é fazer um estudo do léxico no município de Paranaguá-PR, propondo uma discussão sobre manutenção, tendência à manutenção, desuso e tendência ao desuso de lexias extraídas de fontes manuscritas setecentistas, datadas da mesma localidade. Para a realização deste estudo são utilizados, além dos documentos manuscritos digitalizados, dicionários da Língua Portuguesa e material oral. A base teórico-metodológica que norteia esta pesquisa é a da Dialetologia, mas aproxima-se também das utilizadas em pesquisas filológicas (edição de documentos), sociolinguísticas (pesquisa de campo e análise das lexias considerando células sociais) e lexicográficas (elaboração do glossário). Os objetivos específicos são: (i) traçar o panorama histórico da área estudada para auxiliar na compreensão dos aspectos socioculturais, (ii) fazer a edição semidiplomática, acompanhada da reprodução fac-similar dos documentos manuscritos, servindo de base para a caracterização do estado da língua setecentista; (iii) elaborar o glossário visando apresentar a definição dos itens lexicais selecionados com acepções e abonações extraídas do corpus escrito; (iv) investigar as lexias selecionadas por meio dos dados orais coletados com auxílio do questionário semânticolexical, adotando para a seleção dos informantes as variáveis sociais: faixa etária, sexo, naturalidade e grau de escolaridade; e, por fim, (v) verificar, a partir das lexias testadas, o grau de manutenção, tendência à manutenção, desuso e tendência ao desuso, em relação às acepções registradas nos documentos em questão. Tomando por base a análise do contexto de fala dos informantes de Paranaguá, constatou-se que há, no geral, a tendência ao desuso das lexias extraídas do corpus escrito, principalmente por parte dos informantes da primeira faixa etária. Em suma, espera-se que os resultados dessa pesquisa possam contribuir e, ao mesmo tempo, fornecer dados confiáveis aos estudos linguísticos sobre o estado de língua escrita no período setecentista e seus ecos na variedade portuguesa falada em Paranaguá e, por extensão, no Brasil. / The overall objective of this thesis is to study the lexicon in the city of Paranaguá-PR, proposing a discussion on maintenance, tendency to maintenance, disuse and tendency to disuse of lexicon extracted from eighteenth-century manuscript sources, dating from the same locality. For this study, in addition to scanned handwritten documents, dictionaries of Portuguese and oral material are used. The theoretical and methodological basis that guides this research is the Dialectology, but also the basis used in philological research (document editing), sociolinguistic research (field research and analysis of lexicon considering social cells) and lexicographic research (preparing the glossary) .The specific objectives are: (i) to trace the historical background of the study area to assist in understanding the socio-cultural aspects, (ii) to do the semi-diplomatic editing, followed by facsimile reproduction of the handwritten documents, providing the basis for characterizing the state of eighteenth-century language, (iii) to select the lexicon to be tested in the city of Paranaguá, and, from them, to prepare the glossary seeking to present the definition of lexical items with meanings and accreditations extracted from the written corpus , (iv) to collect oral data with the aid of a lexical-semantic questionnaire, adopting for the selection of informants the following social variables: age, sex, place of birth and education level, and finally (v) to verify, from the lexicon tested, the level of maintenance, tendency to maintenance, disuse and tendency to disuse, regarding the meanings recorded in the documents in question. Based on the analysis of the context of the speech of informants from Paranaguá, it was found that, in general, there is a tendency to disuse of lexicon extracted from the written corpus, especially by the informants from the first age group. In short, it is expected that the results of this research can contribute and, at the same time, provide reliable data for linguistic studies on the state of written language during the eighteenth century and its echoes on the Portuguese variety spoken in Paranaguá and, by extension, in Brazil.

O objetivo geral desta tese é fazer um estudo do léxico no município de Paranaguá-PR, propondo uma discussão sobre manutenção, tendência à manutenção, desuso e tendência ao desuso de lexias extraídas de fontes manuscritas setecentistas, datadas da mesma localidade. Para a realização deste estudo são utilizados, além dos documentos manuscritos digitalizados, dicionários da Língua Portuguesa e material oral. A base teórico-metodológica que norteia esta pesquisa é a da Dialetologia, mas aproxima-se também das utilizadas em pesquisas filológicas (edição de documentos), sociolinguísticas (pesquisa de campo e análise das lexias considerando células sociais) e lexicográficas (elaboração do glossário). Os objetivos específicos são: (i) traçar o panorama histórico da área estudada para auxiliar na compreensão dos aspectos socioculturais, (ii) fazer a edição semidiplomática, acompanhada da reprodução fac-similar dos documentos manuscritos, servindo de base para a caracterização do estado da língua setecentista; (iii) elaborar o glossário visando apresentar a definição dos itens lexicais selecionados com acepções e abonações extraídas do corpus escrito; (iv) investigar as lexias selecionadas por meio dos dados orais coletados com auxílio do questionário semânticolexical, adotando para a seleção dos informantes as variáveis sociais: faixa etária, sexo, naturalidade e grau de escolaridade; e, por fim, (v) verificar, a partir das lexias testadas, o grau de manutenção, tendência à manutenção, desuso e tendência ao desuso, em relação às acepções registradas nos documentos em questão. Tomando por base a análise do contexto de fala dos informantes de Paranaguá, constatou-se que há, no geral, a tendência ao desuso das lexias extraídas do corpus escrito, principalmente por parte dos informantes da primeira faixa etária. Em suma, espera-se que os resultados dessa pesquisa possam contribuir e, ao mesmo tempo, fornecer dados confiáveis aos estudos linguísticos sobre o estado de língua escrita no período setecentista e seus ecos na variedade portuguesa falada em Paranaguá e, por extensão, no Brasil. / The overall objective of this thesis is to study the lexicon in the city of Paranaguá-PR, proposing a discussion on maintenance, tendency to maintenance, disuse and tendency to disuse of lexicon extracted from eighteenth-century manuscript sources, dating from the same locality. For this study, in addition to scanned handwritten documents, dictionaries of Portuguese and oral material are used. The theoretical and methodological basis that guides this research is the Dialectology, but also the basis used in philological research (document editing), sociolinguistic research (field research and analysis of lexicon considering social cells) and lexicographic research (preparing the glossary) .The specific objectives are: (i) to trace the historical background of the study area to assist in understanding the socio-cultural aspects, (ii) to do the semi-diplomatic editing, followed by facsimile reproduction of the handwritten documents, providing the basis for characterizing the state of eighteenth-century language, (iii) to select the lexicon to be tested in the city of Paranaguá, and, from them, to prepare the glossary seeking to present the definition of lexical items with meanings and accreditations extracted from the written corpus , (iv) to collect oral data with the aid of a lexical-semantic questionnaire, adopting for the selection of informants the following social variables: age, sex, place of birth and education level, and finally (v) to verify, from the lexicon tested, the level of maintenance, tendency to maintenance, disuse and tendency to disuse, regarding the meanings recorded in the documents in question. Based on the analysis of the context of the speech of informants from Paranaguá, it was found that, in general, there is a tendency to disuse of lexicon extracted from the written corpus, especially by the informants from the first age group. In short, it is expected that the results of this research can contribute and, at the same time, provide reliable data for linguistic studies on the state of written language during the eighteenth century and its echoes on the Portuguese variety spoken in Paranaguá and, by extension, in Brazil.