The nasal passages are constantly exposed to both air- and bloodborne foreign compounds. In particular, the olfactory mucosa is demonstrated to be susceptible to a variety of drugs and chemicals. In this thesis, mechanisms involved in tissue-selective toxicity in the olfactory mucosa of rodents have been investigated using the olfactory toxicant 2,6-dichlorophenyl methylsulphone (2,6-diClPh-MeSO2) as a model compound. Comparative studies were performed with the non-toxic 2,5-dichlorophenyl methylsulphone (2,5-diClPh-MeSO2) and the reasons for the strikingly different toxicity were investigated. A strong bioactivation and protein adduction of 2,6-diClPh-MeSO2 in olfactory microsomes and S9-fractions of rodents was demonstrated. In contrast, no significant metabolic activation of 2,5-diClPh-MeSO2 was observed and the bioactivation in the liver for both chlorinated isomers was negligible. In vitro studies with recombinant yeast cell microsomes expressing mouse cytochrome P450 2A5 (CYP2A5) demonstrated a metabolic activation of 2,6-diClPh-MeSO2. The 2,6-diClPh-MeSO2-induced lesions and CYP2A5 expression preferentially occurred in Bowman’s glands and sustentacular cells of the olfactory mucosa. A significant depletion of glutathione (GSH) in the olfactory mucosa was demonstrated in vivo, while no changes were observed in the liver. There was a rapid induction of the endoplasmic reticulum (ER)-specific chaperone Grp78, activation of the ER-specific caspase-12 and the downstream caspase-3 in the Bowman’s glands. Electron microscopy revealed swelling of ER and mitochondria and a lost integrity of the Bowman’s glands. Based on these results, the proposed mechanism for 2,6-diClPh-MeSO2-induced toxicity in the olfactory mucosa is bioactivation by CYP2A5 into a reactive intermediate causing protein adduction and GSH-depletion. This is initiating a sequence of downstream events of ER-stress, changes in ion homeostasis, ultrastructural organelle disruption and apoptotic signalling. In spite of the initial apoptotic signals, the terminal phase of apoptosis seemed to be blocked and necrotic features occurred. The predominant expression of CYP2A5 in the olfactory mucosa is proposed to play a key role for the tissue- and cell-specific toxicity induced by 2,6-diClPh-MeSO2.

In der vorliegenden Arbeit wurde Gewebe aus den Nasennebenhöhlen von Patienten mit Nasenpolypen untersucht. Außerdem wurden Zusammenhänge zwischen den Zellpopulationen und den Angaben zu allergischen Erkrankungen und wiederholtem Auftreten der Polypen analysiert. Es fand sich eine interindividuell unterschiedlich starke Infiltration mit eosinophilen Granulozyten. Es konnten keine Unterschiede in der prozentualen Verteilung von eosinophilen Granulozyten im Polypengewebe bei allergischen/ nichtallergischen Patienten oder Patienten mit/ ohne Rezidiv nachgewiesen werden. Die Untersuchungen erfolgten mit dem Laser Scanning Zytometer (LSC), das mit der Standardmethode, der Begutachtung mittels Lichtmikroskop, verglichen wurde. Mit der beschriebenen Methode erfolgte die Untersuchung von Polypengewebe nach einem speziell für diese Anwendung entwickelten Protokoll. Die Ergebnisse korrelierten gut mit den Ergebnissen der Lichtmikroskopie. Aufgrund der Weiterentwicklung des LSC und der ständig wachsenden Anzahl der Nachweismöglichkeiten der an der Polyposis nasi beteiligten Zytokine stellt das LSC eine ideale Methode für die Erforschung der Pathogenese von chronischen Entzündungen der Nasennebenhöhlen dar.

Previous studies have demonstrated that chitosan and its derivative, N-trimethyl chitosan chloride (TMC) are effective and safe absorption enhancers to improve mucosal delivery of macromolecular drugs including vaccines. Furthermore, chitosan and TMC can easily form microparticles and nanoparticles, which have the ability to encapsulate large amounts of antigens. Emzaloid™ technology has proven in the past to be an effective delivery system for numerous drugs. Emzaloids can entrap, transport and deliver large amounts of drugs including vaccines. In this study, the ability of chitosan microparticles and nanoparticles, TMC microparticles as well as micrometer and nanometer range Emzaloids to enhance both the systemic and mucosal (local) immune response against diphtheria toxoid (DT) after nasal administration in mice was investigated. The above mentioned formulations were prepared and characterised according to size and morphology. DT was then associated to the chitosan microparticles and nanoparticles as well as TMC microparticles to determine the antigen loading and release. It was found that the loading efficacy of the formulations was 88.9 %, 27.74 % and 63.1 % respectively, and the loading capacity of the formulations was 25.7 %, 8.03 % and 18.3 %. DT loaded and unloaded (empty) chitosan microparticles and nanoparticles, TMC microparticles, micrometer and nanometer range Emzaloids as well as DT in phosphate buffered saline (PBS) were administered nasally to mice. Mice were also vaccinated subcutaneous with DT associated to alum as a positive control. All mice were vaccinated on three consecutive days in week 1 and boosted in week 3. Sera was analysed for anti- DT IgG and nasal lavages were analysed for anti-DT IgA using an enzyme linked imrnunosorbent assay (ELISA). In the study conducted to determine the systemic (IgG) and local (IgA) immune responses it was seen that DT associated to all the experimental formulations produced a systemic immune response. The said formulations produced a significantly higher systemic immune response when compared to the formulation of DT in PBS. Furthermore, the mice vaccinated with DT associated to the TMC formulations showed a much higher systemic immune response than the mice that were vaccinated subcutaneously with DT associated to alum, whereas the other formulations produced systemic immune responses that were comparable to that of DT associated to alum. It was also found that DT associated to the experimental formulations produced a local immune response, however only DT associated to TMC microparticles produced a consistent local immune response. It can be concluded from the in vivo experiments that the TMC formulations, moreover, the TMC microparticles is the most effective and promising formulation for the nasal delivery of vaccines. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

Previous studies have demonstrated that chitosan and its derivative, N-trimethyl chitosan chloride (TMC) are effective and safe absorption enhancers to improve mucosal delivery of macromolecular drugs including vaccines. Furthermore, chitosan and TMC can easily form microparticles and nanoparticles, which have the ability to encapsulate large amounts of antigens. Emzaloid™ technology has proven in the past to be an effective delivery system for numerous drugs. Emzaloids can entrap, transport and deliver large amounts of drugs including vaccines. In this study, the ability of chitosan microparticles and nanoparticles, TMC microparticles as well as micrometer and nanometer range Emzaloids to enhance both the systemic and mucosal (local) immune response against diphtheria toxoid (DT) after nasal administration in mice was investigated. The above mentioned formulations were prepared and characterised according to size and morphology. DT was then associated to the chitosan microparticles and nanoparticles as well as TMC microparticles to determine the antigen loading and release. It was found that the loading efficacy of the formulations was 88.9 %, 27.74 % and 63.1 % respectively, and the loading capacity of the formulations was 25.7 %, 8.03 % and 18.3 %. DT loaded and unloaded (empty) chitosan microparticles and nanoparticles, TMC microparticles, micrometer and nanometer range Emzaloids as well as DT in phosphate buffered saline (PBS) were administered nasally to mice. Mice were also vaccinated subcutaneous with DT associated to alum as a positive control. All mice were vaccinated on three consecutive days in week 1 and boosted in week 3. Sera was analysed for anti- DT IgG and nasal lavages were analysed for anti-DT IgA using an enzyme linked imrnunosorbent assay (ELISA). In the study conducted to determine the systemic (IgG) and local (IgA) immune responses it was seen that DT associated to all the experimental formulations produced a systemic immune response. The said formulations produced a significantly higher systemic immune response when compared to the formulation of DT in PBS. Furthermore, the mice vaccinated with DT associated to the TMC formulations showed a much higher systemic immune response than the mice that were vaccinated subcutaneously with DT associated to alum, whereas the other formulations produced systemic immune responses that were comparable to that of DT associated to alum. It was also found that DT associated to the experimental formulations produced a local immune response, however only DT associated to TMC microparticles produced a consistent local immune response. It can be concluded from the in vivo experiments that the TMC formulations, moreover, the TMC microparticles is the most effective and promising formulation for the nasal delivery of vaccines. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

Diss. (sammanfattning) Umeå : Univ., 2007. / Härtill 4 uppsatser.

Esta tese investiga a aquisição fonológica variável da nasal velar em coda silábica final (como em living ‘vivendo’ e singing ‘cantando’, por exemplo) por aprendizes brasileiros de inglês como segunda língua. O estudo é motivado pela diferença de status da nasal velar em português (L1, primeira língua) e inglês (L2, segunda língua): enquanto na L1 o segmento é realização fonética resultante de assimilação de ponto de articulação (como em atum, em que a nasal bilabial assimila o traço [+dorsal] da vogal precedente realizando-se como velar), na L2 a nasal velar é fonema (como em sin ‘pecado’ x sing ‘cantar’, realizados com a nasal alveolar e velar, respectivamente). Em algumas comunidades de falantes nativos de inglês, palavras derivadas pelo sufixo {ing} (como read.ing ‘lendo’ e study.ing ‘estudando’, por exemplo) constituem um fenômeno de variação linguística estável, em que os falantes alternam a produção das nasais velar e alveolar no final das palavras. Essa variação é estrutural e socialmente condicionada (LABOV, 1994; 2001). Os dados empíricos deste estudo provêm da fala coletada através de gravações com aprendizes de inglês, que pertecem a dois níveis de proficiência: básico e pré-intermediário. São realizadas duas análises formais: uma que explica a variação sistemática na interlíngua, observável no desempenho dos aprendizes, através do software Goldvarb (SANKOFF, TAGLIAMONTE e SMITH, 2015), e outra que formaliza a organização interna dessa gramática variável, através de algoritmos de aprendizagem vinculados à Teoria da Otimidade Estocástica, o Algoritmo de Aprendizagem Gradual (GLA) (BOERSMA e HAYES, 2001) e o ORTO Ajuste Paramétrico (DORNELLES FILHO, 2014). A Análise de Regra Variável demonstrou que a interlíngua é um sistema linguístico sujeito à variação ordenada como as demais línguas naturais, condicionada por aspectos linguísticos (classe morfológica) e extralinguísticos (nível de proficiência). A variação é verificada pela produção oral dos aprendizes, examinada de oitiva, que alterna as nasais palatal (63,6%) e velar (36,4%) em coda silábica final. A análise estocástica revelou um sistema de interlíngua dominado por restrições de Marcação, cuja variação é decorrente do aumento dos valores de ponto de seleção de restrições de Fidelidade. As restrições diretamente envolvidas na aquisição fonológica variável da nasal velar são AGREEplaceVN#, que exige que a sequência Vogal+Nasal em coda final partilhem ponto de articulação, e IDENTnasal, que requer identidade de traço nasal entre as formas presentes no input e no output. As análises realizadas, que representam a língua dos aprendizes em seus aspectos interno e externo, ou, conforme a terminologia de Chomsky ([1965]1 1975), a competência e o desempenho linguísticos, comprovaram a natureza variável da interlíngua e proporcionaram uma reflexão teórica acerca da possibilidade de diálogo entre o estrutural e o social para a explicação de fenômenos linguísticos variáveis. / This thesis investigates the variable phonological acquisition of the velar nasal in final syllabic coda (such as in living ‘vivendo’ and singing ‘cantando’, for example) by Brazilian learners of English as a second language. The study is motivated by the different status of the velar nasal in Portuguese (L1, first language) and in English (L2, second language): while the segment is a phonetic realization of assimilation of place of articulation in the L1 (‘atum’, where the bilabial nasal assimilates the feature [+dorsal] of the preceding vowel, being realized as velar), the velar nasal is a phoneme in the L2 (sin ‘pecado’ x sing ‘cantar’, realized as the alveolar and velar nasal, respectively). In some native English-speaking communities, words derived from the suffix {ing} (such as read.ing ‘lendo’, study.ing ‘estudando’, for example) are in linguistic stable variation, in which the speakers alternate the production of the alveolar and velar nasal the velar nasal at the end of words. This variation is both structurally and socially conditioned (LABOV, 1994; 2001). The empirical data of this study were collected through recordings with the informants, who belong to two levels of proficiency: basic and pre-intermediate. Two formal analysis are made: one that explains the observable systematic variation in the Interlanguage, through the software Goldvarb (SANKOFF, TAGLIAMONTE and SMITH, 2015) and another that formalizes the internal organization of this variable grammar, through gradual learning algorithms associated to the Stochastic Optimality Theory, the Gradual Learning Algorithm (GLA) (BOERSMA and HAYES, 2001) and the ORTO Ajuste Paramétrico (DORNELLES FILHO, 2014). The Variable Rule Analysis has demonstrated that interlanguage is a linguistic system subject to ordered variation as in all the other natural languages, conditioned by linguistic aspects (morphological class) and extralinguistic ones (level of proficiency). The variation is verified by the oral production of the learners, examined by hearing analysis, which alternates the palatal nasal (63,6%) The stochastic analysis has revealed an Interlanguage system dominated by Markedness constraints, where variation is due to the increase on the values of selection points for Faithfulness constraints. The constraints directly involved in the variable phonological acquisition of the velar nasal are AGREEplaceVN#, which demands the sequence Vowel+Nasal in final coda to share place of articulation, and IDENTnasal, which demands feature identity [+nasal] between input and output forms. The analyses made, which represent the learners’ language in its internal and external aspects, or, according to Chomsky’s terminology ([1965] 1975), the linguistic competence and performance, have proved the variable nature of the Interlanguage and have enabled a theoretical reflection upon the possibility of dialogue between the structural and the social to the explanation of variable linguistic phenomena.

O trabalho tem como tema o estudo da variação do ditongo nasal ão em sílaba final de vocábulo (ex. pão ~ pon; tiravam ~ tiravon) por falantes bilíngues de português-alemão e português-italiano das comunidades de Panambi e Flores da Cunha, respectivamente. A decisão por investigar essas comunidades deve-se à constatação preliminar de que tal fenômeno é característico de comunidades bilíngues cujas línguas de origem não possuem ditongos nasais. A amostra constitui-se de 16 entrevistas do PROJETO VARSUL (Variação Linguística Urbana na Região Sul). Dados do PROJETO ALERS (Atlas Linguístico-Etnográfico da Região Sul do Brasil) de comunidades bilíngues de alemão e de italiano contribuíram para enriquecer a discussão. No presente estudo, a variável dependente, a alternância do ditongo nasal ão/am ~on em final de vocábulo, é examinada frente a possíveis condicionadores linguísticos e extralinguísticos, suas variáveis independentes. As variáveis linguísticas analisadas são Tonicidade do Alvo, Extensão do Vocábulo, Classe Gramatical, Número (Singular ou Plural) e Contexto Precedente. De forma geral, o fenômeno se aplica em sílabas finais tônicas de palavras no singular, fazendo uma leve distinção entre palavras longas e curtas. Além disso, como se trata de uma variação fonética de superfície, a classe gramatical não parece ser relevante nesse processo, ainda que deva incidir mais significativamente sobre alguns itens lexicais em específico. Quanto às variáveis extralinguísticas, foram analisados Localidade Bilíngue, Idade, Sexo e Escolaridade. De forma geral, o processo não faz distinção importante entre as duas localidades bilíngues analisadas, mas se aplica mais entre os menos escolarizados, por seu menor contato com a modalidade padrão da língua portuguesa. Além disso, o processo aplica-se mais entre homens com mais de 50 anos, em virtude de seu grau de bilinguismo e, possivelmente, por as mulheres dessas comunidades evitarem mais do que os homens variantes desprestigiadas. Os resultados foram analisados estatisticamente pelo programa GOLDVARB X e discutidos na perspectiva da Teoria da Variação, proposta por Labov (1969, 1972). / This dissertation deals with the variation of the nasal diphthong [ãw] in final syllable of word position (ex. pão ~ pon; tiravam ~ tiravon) by bilingual speakers of German and Italian communities from Panambi and Flores da Cunha, respectively. The decision to investigate these communities due to the preliminary conclusion, that this phenomenon is characteristic of bilingual communities whose languages of origin do not have nasal diphthongs. The sample is constituted of 16 interviews from VARSUL PROJECT (Urban Linguistic Variation in South Region). Data from ALERS PROJECT (Linguistic-Ethnographic Atlas of Southern Brazil) communities bilingual German and Italian contributed to enrich the discussion. In this study, the dependent variable, the alternation of the nasal diphthong ão/am ~ on at the end of word, is examined against possible linguistic and extra linguistic conditioners, their independent variables. The linguistic variables analyzed are Target Toning, Extension of the Word totally, Grammar Class, Number (singular or plural) and Previous Context. In general, the phenomenon applies in tonic final syllables of words in the singular, making a slight distinction between long and short words. Moreover, as it is a phonetic variation of surface, the grammar class is not relevant in this process, although it should focus more significantly on some lexical items in particular. Concerning to the extralinguistic variables, were analyzed bilingual Place, Age, Gender and Education. In general, the process does not distinguish between the two major bilingual cities analyzed, but applies more among the less educated, on the slightest contact with the standard form of the Portuguese language. Furthermore, the process applies more among men over 50 years, because of their degree of bilingualism and, possibly, by the fact the women these communities more than men discredited variants. The results were statistically analyzed by the GOLDVARB X and discussed from the perspective of the Theory of Change, proposed by Labov (1969, 1972).

Made available in DSpace on 2016-12-23T13:56:02Z (GMT). No. of bitstreams: 1 saliba impressaofinalissima.pdf: 1761805 bytes, checksum: f8ae03fbaec42d9fb5d3e49e0cf7c65b (MD5) Previous issue date: 2007-12-27 / Embora raramente se associem com complicações graves, as rinossinusopatias acarretam grande morbidade, absenteísmo laboral e escolar e grande custo financeiro. Em nível local, há poucos estudos clínicos descritivos sobre manifestações clínicas, otimização de métodos e critérios diagnósticos e sobre o perfil de comorbidade segundo a etiopatogênese (estrutural, funcional, alérgica ou infecciosa). Objetivo: descrever comparativamente os achados clínicos, do transporte mucociliar, citopatológicos, do teste cutâneo para alérgenos, endoscópicos e imaginológicos. Casuística e métodos: 212 casos recrutados dentre 2549 pacientes atendidos no Hospital da Polícia Militar e no Centro de Otorrinolaringológico, em Vitória, ES, entre 3 de janeiro de 2005 e 11 de maio de 2006; 10 tabagistas e 10 não tabagistas sem queixas rinossinusais foram adicionalmente recrutados para comparação. Os achados foram sumarizados como freqüências absoluta e relativa simples de acordo com o grupo etiopatogênico. Resultados: anormalidade estrutural foi identificada em 10 (4,7%), funcional em 11 (5,2%), alérgica em 28 (13,2%), infecciosa em 13 (6,1%), mais de uma das precedentes em 136 (64,1%) e outras doenças em 14 (6,6%). Dentre as 612 comparações analisadas, 19% mostraram freqüência com incremento direto maior que 20% entre os grupos: rinossinusite, rinite alérgica, anormalidade anatômica e funcional. Conclusão: estes resultados demonstram que a comorbidade é a regra e os achados, similares e sobrepostos entre as várias rinossinusopatias, demandam, para a sua distinção, a consideração concomitante dos aportes da história clínica, citopatologia, transporte mucociliar, endoscopia nasal e imaginologia. / Rhinosinusal illnesses are associated with a great morbidity, high costs for the patients and high tax of labor and school absenteeism. Even though these illnesses are well known, there is few descriptive studies about the clinical manifestations, the optimization of the diagnostic criteria and the distribution of comorbidity according to the etiopathogenic types (structural, functional, allergic and infectious) at a local level. Objective: to carry through a comparative description of the clinical, mucociliary clearance, citopathologic, endoscopic and imaginologic findings of the rhinosinusal illness at local doctors office. Patients and methods: 232 of a universe of 2549 patients taken care at two otorrhinolaringologic clinics at Vitória citty, Espírito Santo State, Brazil, from January, 3rd of 2005 to May, 11th of 2006. Of 232, 212 were patients with some rhinosinusal complaints and 20 citizens without rhinosinusal complaints (10 smokers and 10 nonsmokers) were used as control group. The absolute and relative frequency of clinical and laboratory findings were compared between the ethiopathogenic types of rhinosinusal illness. Results: structural abnormalities was present in 10 (4,7%), functional abnormalities in 11 (5,2%), allergy in 28 (13,2%) and infection in 13 (6,1%); in 136 (64,1%) there is more than one of these conditions. Among the 612 findings analised, 19% shows direct increment of frequency higher than 20% between the rhinosinusal types: rhinosinusitis, allergic rhinitis, structural and functional abnormalities. Conclusion: these results show that comorbidity is high and that there is great overlapping of findings between the various types of rhinosinusal illness. To discriminate between them is necessary to take account of concommitant contribution of the clinical history, cytopathology, mucociliary clearance, endoscopic and imaginologic findings.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-01-03T20:58:46Z No. of bitstreams: 1 MorganaDeAraujoEvangelista_DISSERT.pdf: 2607941 bytes, checksum: 7cff1386828e64e1f63b7ce32b375bb0 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-01-09T14:10:37Z (GMT) No. of bitstreams: 1 MorganaDeAraujoEvangelista_DISSERT.pdf: 2607941 bytes, checksum: 7cff1386828e64e1f63b7ce32b375bb0 (MD5) / Made available in DSpace on 2017-01-09T14:10:37Z (GMT). No. of bitstreams: 1 MorganaDeAraujoEvangelista_DISSERT.pdf: 2607941 bytes, checksum: 7cff1386828e64e1f63b7ce32b375bb0 (MD5) Previous issue date: 2015-06-17 / INTRODU??O: A Distrofia Miotonica ? caracterizada por atrofia, fraqueza presen?a de miotonia nos m?sculos esquel?ticos. A presen?a de miotonia nos musculos respirat?rios ? duvidosa assim como as t?cnicas para avalia-l?s. OBJETIVOS: Avaliar a sensibilidade /especificidade da taxa m?xima de relaxamento dos m?sculos inspirat?rios (MRR), a eletromiografia de superf?cie (EMGs) dos m?sculos esternocleidomast?ideo (SCM), escaleno (ESC), paraesternal (2EIC), reto abdominal (RA) e a fun??o pulmonar/muscular respiratoria em pacientes com DM1 e sujeitos saudaveis. M?TODOS: Foram convidados a participar do estudo, 71 indiv?duos, 44 pacientes com DM1 e 27 controles. Foram inclu?dos no estudo 28 sujeitos, (18 DM1 e 10 controles). Ap?s exlcus?es a amostra final foi de 25 sujeitos, 16 pacientes com DM1 e 9 sujeitos saud?veis. Todos foram avaliados em rela??o MRR dos m?sculos inspirat?rios, (dP/dt)/Psniff*100(%10ms), a EMGs dos m?sculos respirat?rios, ? fun??o muscular e pulmonar. RESULTADOS: A MRR foi menor nos pacientes com DM1 vs. controle (p=0,003) e foi considerada sens?vel e espec?fica para identificar a doen?a na DM1 e descart?-la no grupo controle, ?rea de ROC 0,87 (95%IC, 0,729 a 1,01, p=0,003). Foi observado valores reduzidos de PIm?x (p=0,0029), PEm?x (p=0,0007) e SNIP (p=0,0030), CVF%pred. (p=0,0014) e VEF1%pred. (p=0,0003) e maior atividade da EMGs em repouso nos m?sculos SCM (p=0,004), ESC (p=0,009) e RA (p=0,045) e no m?sculo SCM (p=0,001) durante o sniff teste. CONCLUS?ES: A MRR ? sensivel e especifica para identificar atraso no relaxamento dos musculos respirat?rios e a fun??o muscular respirat?ria encontra-se alterada nos pacientes com DM1. / INTRODUCTION: Myotonic dystrophy (DM) is a neuromuscular disease characterized by unstable expansion of CTG triplet on chromosome 19. It has two forms: type 1 (DM1 or Steinert's disease); and type 2 (DM2), being the former the most frequent and showing systemic manifestations, such as myotonia (muscle relaxation difficulty), cataracts, arrhythmias, muscle weakness and atrophy, among others, respiratory failure being one of the main factors predictive of mortality and a leading cause of death. OBJECTIVES: To evaluate the sensitivity / specificity of the maximum relaxation rate of the inspiratory muscles (MRR), the surface electromyography (sEMG) of the sternocleidomastoid (SCM), scalene (SCA), parasternal (2ICS), rectus abdominis (RA) and lung function/respiratory muscle strength in patients with DM1 and healthy subjects. METHODS: We invited 74 subjects to participate in the study, 44 patients with DM1 and 30 controls. The study included 31 subjects (18 DM1 and 13 controls). After exclusions, the final sample was of 27 subjects, 16 patients with DM1 and 11 healthy subjects. All of them were assessed for MRR of inspiratory muscles, for sEMG of the respiratory muscles, muscle and lung function. RESULTS: The MRR was lower in patients with DM1 vs. control (p = 0.001) and was considered sensitive and specific to identify the disease in DM1 and discard it in the control group, ROC area of 0.87 (95% CI, 0.74 to 1.01, p=0.001). DM1 group showed lower PImax (p=0.0006), PEmax (p=0.0002), SNIP (p=0.0014), CVF%pred (p=0.0018) and FEV1%pred. (p=0.0004) and higher sEMG activity of the SCM (p=0.0022) and ESC muscles (p=0.004) at rest; of 2EIC (p=0.003) during PEmax and of SCM (p=0.02) and ESC muscles (p= 0.03) during the sniff test. CONCLUSIONS: The MRR is sensitive and specific to identify delayed relaxation of the respiratory muscles and respiratory muscle function is altered in patients with DM1.

O trabalho tem como tema o estudo da variação do ditongo nasal ão em sílaba final de vocábulo (ex. pão ~ pon; tiravam ~ tiravon) por falantes bilíngues de português-alemão e português-italiano das comunidades de Panambi e Flores da Cunha, respectivamente. A decisão por investigar essas comunidades deve-se à constatação preliminar de que tal fenômeno é característico de comunidades bilíngues cujas línguas de origem não possuem ditongos nasais. A amostra constitui-se de 16 entrevistas do PROJETO VARSUL (Variação Linguística Urbana na Região Sul). Dados do PROJETO ALERS (Atlas Linguístico-Etnográfico da Região Sul do Brasil) de comunidades bilíngues de alemão e de italiano contribuíram para enriquecer a discussão. No presente estudo, a variável dependente, a alternância do ditongo nasal ão/am ~on em final de vocábulo, é examinada frente a possíveis condicionadores linguísticos e extralinguísticos, suas variáveis independentes. As variáveis linguísticas analisadas são Tonicidade do Alvo, Extensão do Vocábulo, Classe Gramatical, Número (Singular ou Plural) e Contexto Precedente. De forma geral, o fenômeno se aplica em sílabas finais tônicas de palavras no singular, fazendo uma leve distinção entre palavras longas e curtas. Além disso, como se trata de uma variação fonética de superfície, a classe gramatical não parece ser relevante nesse processo, ainda que deva incidir mais significativamente sobre alguns itens lexicais em específico. Quanto às variáveis extralinguísticas, foram analisados Localidade Bilíngue, Idade, Sexo e Escolaridade. De forma geral, o processo não faz distinção importante entre as duas localidades bilíngues analisadas, mas se aplica mais entre os menos escolarizados, por seu menor contato com a modalidade padrão da língua portuguesa. Além disso, o processo aplica-se mais entre homens com mais de 50 anos, em virtude de seu grau de bilinguismo e, possivelmente, por as mulheres dessas comunidades evitarem mais do que os homens variantes desprestigiadas. Os resultados foram analisados estatisticamente pelo programa GOLDVARB X e discutidos na perspectiva da Teoria da Variação, proposta por Labov (1969, 1972). / This dissertation deals with the variation of the nasal diphthong [ãw] in final syllable of word position (ex. pão ~ pon; tiravam ~ tiravon) by bilingual speakers of German and Italian communities from Panambi and Flores da Cunha, respectively. The decision to investigate these communities due to the preliminary conclusion, that this phenomenon is characteristic of bilingual communities whose languages of origin do not have nasal diphthongs. The sample is constituted of 16 interviews from VARSUL PROJECT (Urban Linguistic Variation in South Region). Data from ALERS PROJECT (Linguistic-Ethnographic Atlas of Southern Brazil) communities bilingual German and Italian contributed to enrich the discussion. In this study, the dependent variable, the alternation of the nasal diphthong ão/am ~ on at the end of word, is examined against possible linguistic and extra linguistic conditioners, their independent variables. The linguistic variables analyzed are Target Toning, Extension of the Word totally, Grammar Class, Number (singular or plural) and Previous Context. In general, the phenomenon applies in tonic final syllables of words in the singular, making a slight distinction between long and short words. Moreover, as it is a phonetic variation of surface, the grammar class is not relevant in this process, although it should focus more significantly on some lexical items in particular. Concerning to the extralinguistic variables, were analyzed bilingual Place, Age, Gender and Education. In general, the process does not distinguish between the two major bilingual cities analyzed, but applies more among the less educated, on the slightest contact with the standard form of the Portuguese language. Furthermore, the process applies more among men over 50 years, because of their degree of bilingualism and, possibly, by the fact the women these communities more than men discredited variants. The results were statistically analyzed by the GOLDVARB X and discussed from the perspective of the Theory of Change, proposed by Labov (1969, 1972).