Orientadores: Ester Maria Danielli Nicola, Eulália Sakano / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T13:39:38Z (GMT). No. of bitstreams: 1 Ortiz_Erica_D.pdf: 2854168 bytes, checksum: c4f7e3d14049e592b11a3b339481fa12 (MD5) Previous issue date: 2014 / Resumo: Introdução: Acredita-se que a imunossupressão seja única causa para maior prevalência de rinossinusites (RS) no transplantado de células tronco hematopoiéticas (TCTH) principalmente naqueles com Doença do Enxerto contra o Hospedeiro (DECH) crônica. Pacientes submetidos ao TCTH podem apresentar alterações nasossinusais, que podem se relacionar ao próprio transplante, assim como pelo regime de condicionamento ou pela DECH. Entretanto, estas alterações nasossinusais não estão bem descritas na literatura assim como a associação entre estas e a rinossinusite. Objetivo: verificar a histologia e ultraestrutura da mucosa nasossinusal com RS no TCTH com e sem DECH; e verificar a influencia da RS nas possíveis alterações histológicas nestes pacientes. Método: estudo prospectivo exploratório de coorte transversal com análise estatística de dados obtidos da avaliação de mucosa de processo unciforme de pacientes transplantados com (16) e sem DECH (8) com RS; através da microscopia eletrônica de transmissão e óptica. Comparação da recorrência das RS e alterações histológicas. Resultados: 47% (14) tiveram apenas 1 ou 2 episódios e 33%, mais de 3 episódios de rinossinusite. Apenas a presença de microvilosidades foi significativamente maior nos pacientes sem GVHD (p=0,05). Não houve diferença significativa na quantidade de cílios, ultraestrutura ciliar, metaplasia escamosa, células caliciformes, vacuolização citoplasmática, densidade do infiltrado inflamatório, linfócitos, eosinófilos e corpúsculos apoptóticos intraepiteliais, glândulas mucosas, espessura da membrana basal, edema e fibrose subepiteliais entre os grupos com e sem DECH. Houve diminuição significante de cílios conforme maior recorrência de rinossinusite (p=0,008). Conclusão: pacientes com RS e TCTH não apresentaram diferenças nas alterações histológicas nasossinusais, exceto aumento de microvilosidades naqueles sem a DECH. Os transplantados com e sem DECH apresentaram somente diminuição dos cílios conforme o aumento da recorrência de RS / Abstract: INTRODUCTION: It is believed that immunosuppression is the sole cause for the occurrence of rhinosinusitis in hematopoietic stem cell transplant (HSCT). There is a high incidence of sinusitis in recipient patients, especially in those with Chronic Graft-Versus-Host disease (GVHD). Histopathological abnormalities were described in recipients¿ sinus mucosa compared to immunocompetent patients. There were also mucosal abnormalities related to cytotoxicity in the transplanted patients with chronic GVHD but no difference in ultrastructure between HSCT patients with and without GVHD, except for increased goblet cells in patients without GVHD. The relation between the sinonasal mucosa abnormalities of patients with and without GVHD and rhinosinusitis is not well established yet. OBJECTIVE: To verify the ultrastructure of the sinonasal mucosa of HSCT with and without GVHD with rhinosinusitis to understand the cause of high sinusitis incidence in recipients with and without GVHD. METHOD: A prospective study with preliminary exploratory statistical analysis of data obtained from the evaluation of the uncinate process mucosa of patients transplanted with (16) and without GVHD (8) with rhinosinusitis by transmission electron and optical microscopy. RESULTS: Of the patients, 47% (14) had only 1 or 2 episodes, and 33% had more than 3 episodes of rhinosinusitis. Only the presence of microvilli was significantly higher in patients without GVHD. There was no significant difference in the amount of cilia, ciliary ultrastructure, squamous metaplasia, goblet cells, vacuolization, density of the inflammatory infiltrate, intraepithelial lymphocytes, eosinophils, mucous glands, apoptotic corpuscles intraepithelial basement membrane thickness, edema and subepithelial fibrosis between groups. There was a significant decrease of cilia with higher recurrence of rhinosinusitis. CONCLUSION: There was an increase in microvilli HSCT without GVHD with rhinosinusitis, and the ultrastructure and histological changes of HSCT with and without GVHD did not change with the recurrence of rhinosinusitis. However, there was a decrease of cilia in the epithelium of the sinonasal HSCT with higher recurrence of rhinosinusitis / Doutorado / Otorrinolaringologia / Doutora em Ciências Médicas

Orientador: Eulalia Sakano / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T20:48:54Z (GMT). No. of bitstreams: 1 Ng_RonnyTahYen_M.pdf: 2076573 bytes, checksum: 564de0a72c22446e69acd2aaae6840a7 (MD5) Previous issue date: 2013 / Resumo: A fibrose cística (FC) é uma doença genética autossômica recessiva, resultante da ausência total na proteína CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), ou de alterações qualitativas ou quantitativas do gene que transcreve esta proteína, em células de diversos órgãos do corpo humano, resultando em inúmeros genótipos e fenótipos desta doença. Em muitos pacientes, o diagnóstico é difícil de ser definido, pelo método clássico de dosagem de sódio e cloro no suor, ou pelo sequenciamento genético, justificando a utilização de novas técnicas de auxílio diagnóstico, como a Diferença de Potencial Nasal (DPN). Este teste proporciona uma forma de avaliação direta e sensível, através do epitélio nasal, do transporte de sódio e cloro das membranas celulares, baseado nas propriedades bioelétricas transepiteliais. O objetivo deste trabalho foi verificar se existe diferença dos valores obtidos no exame de DPN em pacientes com FC em comparação com indivíduos controles saudáveis; e verificar se este teste permite diferenciar pacientes com FC das subclasses funcionais mais graves (I, II, III) das subclasses menos graves (IV, V, VI). Foram incluídos no estudo 15 pacientes FC, 10 com mutações mais graves (grupo A) e 5 com mutações menos graves (grupo B), e 21 controles saudáveis (grupo C). Foram considerados os seguintes parâmetros do teste da DPN: "Finger", PDMax, ?Amilorideo, ?Amilorídeo+livrecloreto e index de Wilchanski. Para a variável "Finger", foi encontrada diferença entre pacientes com FC grupo B - mutações menos graves (classe IV, V ou VI) e indivíduos saudáveis - grupo C. O valor do index de Wilchanski mostrou diferença entre pacientes com FC grupo A - mutações mais graves (classes I, II ou III) e indivíduos saudáveis - grupo C. No nosso estudo, a DPN mostrou valores estatisticamente diferentes entre FC com 2 mutações conhecidas e sujeitos saudáveis. Porém, não conseguiu diferenciar fibrocísticos com mutações mais graves (classes I, II e III) daqueles com mutações consideradas menos graves (classes IV, V e VI) / Abstract: Cystic fibrosis (CF) is an autosomal recessive genetic disease, due to the total absence of protein CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), or due to qualitative or quantitative changes in the gene that transcript this protein in cells of various organs of the human body, resulting in numerous genotypes and phenotypes of the disease. In several patients, the diagnosis is difficult to be defined by the classical method of sodium and chloride dosage in sweat, or by genetic sequencing, justifying the use of new techniques for diagnosis, as the Nasal Potential Difference (NPD). This test provides a way of direct and sensitive assessment of the transport of sodium and chloride ions in cell membranes, via the nasal epithelium, based on transepithelial bioelectric properties. The objective of this work was to verify the difference of the values obtained in the examination of NPD in patients with CF compared with healthy control subjects, and, to verify if this test allows differentiating patients with more severe CF functional subclasses (I, II , III) from patients with less severe CF subclasses (IV, V, VI). This study included 15 CF patients, 10 with more severe mutations (group A) and 5 with less severe mutations (group B), and 21 healthy controls (group C). We considered the following test parameters of NPD: "Finger", PDMax, ?Amiloride, ?Amiloríde+Chloridefree and Wilchanski index. For "Finger" values, it was found difference between patients with CF Group B - less severe mutations (class IV , V or VI) and healthy individuals - group C. The value of Wilchanski index showed difference between group A CF patients, with more severe mutations (class I, II or III) and healthy individuals - group C. In our study, NPD showed statistically different values between CF patients with two known mutations and healthy subjects. However, it was not able to distinguish between CF patients with more severe mutations (class I, II and III) of the CF patientswith less severe mutations (Class IV, V and VI) / Mestrado / Otorrinolaringologia / Mestre em Ciências Médicas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In the presence of nasal obstruction, nasal patency may be reduced, and nasal breathing is replaced by mouth breathing (MB). Orofacial, and otorhinolaringologic changes are present in this breathing mode, as well as head posture misalignment, as a compensatory mechanism for the nasal airflow impairment. Some characteristics are typically found, but MB diagnosis is still controversial among multidisciplinary assessments. This study was conduct to identify variables associated with mouth breathing diagnosis in children, based on multidisciplinary domains, including anamnesis, speech therapy, otorhinolaryngologic, occlusal and physiotherapeutic assessments. It also aimed to compare nasal patency and otorhinolaryngologic-orofacial features and craniocervical posture in children. Six-12 year-old children, both sexes underwent muldisciplinary evaluation constituted by: anamnesis; speech therapy evaluation, according to MBGR protocol; clinical and endoscopic otorhinolaryngologic (OTRL) examination; occlusal and physical therapy assessments (nasal patency and body posture). Nasal patency was measured, by means of Peak Nasal Inspiratory Flow absolute (PNIF) values and Nasal Obstruction Symptom Evaluation (NOSE) scale. Craniocervical posture was evaluated with biophotogrametric measures (software SAPO, v.0.68), such as: Cervical Distance (CD); Head Horizontal Alignment (HHA), Flexion-Extension Head Position (FE) and Lumbar Distance (LD). Mann-Whitney, Kruskal-Wallis, Spearman Correlation Coefficient and Multiple Logistic Regression were used for data analysis. One hundred thirty three children took part in the study. Significant lower values of PNIF and %PNIF in children with restless sleep (p=0.006 and p=0.002), nasal obstruction report (p=0.027 and p=0.023) and runny nose (p=0.004 and p=0.012), unsystematic lip closure during mastication (p=0.040 and 0.026), masticatory speed reduced (p=0.006 and p= 0.008) and altered solid food swallowing (p=0.006 and p=0.001) were found. Significant lower PNIF was found in children with pale inferior turbinate (p=0.040). PNIF and %PNIF was significantly higher in children with mild everted lip (p=0.008 and p=0.000). PNIF was significantly higher in children with tongue width increased (p=0.027) and lower in children with hard palate width reduced (p=0.037). PNIF was significantly lower in children with altered speech (p=0.004). FE was significantly higher in children with nasal patency decreased (p=0.023). Negative and weak correlation between FE and %PNIF (r=-0.266; p=0.002) and positive and weak correlation between CD and PNIF (r=0.209; p=0.016) were found. NOSE scores were negatively correlated with PNIF (r= -0.179; p=0.039). It was found association of MB diagnosis in each professional domain with: nasal obstruction report (OR =5.55), time of pacifier sucking (OR=1.25), convex facial type (OR=3.78), obtuse nasal angle (OR=4.30), half-open or open lip posture (OR=4.13), tongue positioned on the mouth floor (OR=5.88), hard palate width reduced (OR=2.99), unexpected contraction of orbicularis and mentalis muscles during mastication (OR= 2.97), obstructive pharyngeal tonsills (OR=8.37), Angle Class II malocclusion (OR= 10.85) and regular gingival maintenance (OR=2.89). Nasal patency was lower in children with restless sleep, rhinitis signs and symptoms, hard palate width reduced and with changes in mastication, deglutition and speech functions. Children with decreased nasal patency presented greater head extension and, this postural deviation is prone to increase as nasal airflow decreases, indicating the relationship between craniocervical posture and nasal patency. Nasal obstruction report, time of pacifier sucking, convex facial type, obtuse nasal angle, half-open or open lip posture, tongue positioned on the mouth floor, hard palate width reduced, unexpected contraction during mastication, obstructive pharyngeal tonsils, Angle Class II malocclusion and regular gingival maintenance were associated with MB diagnosis / Na presença de uma obstrução nasal, a permeabilidade pode estar reduzida e a respiração nasal é substituída pela respiração oral (RO). Alterações orofaciais e otorrinolaringológicas são associadas a essa condição, bem como alterações na postura da cabeça, como mecanismo compensatório a redução do fluxo nasal. Algumas características são tipicamente associadas a RO, mas seu diagnóstico ainda permanece controverso. Este estudo foi conduzido para identificar variáveis associadas com o diagnóstico de respiração oral em crianças, baseado nos domínios multidisciplinares. Também se propôs a comparar a permeabilidade nasal e as características orofaciais, fonoaudiológicas e postura craniocervical em crianças. Um total de 133 crianças de seis a 12 anos de idade, de ambos os sexos, submeteram-se avaliação multidisciplinar constituída de: anamnese; avaliação fonoaudiológica, de acordo com o protocolo MBGR; exame OTRL clínico e endoscópico; avaliações oclusal e fisioterapêutica (permeabilidade nasal e postura corporal). A permeabilidade nasal foi medida por meio do Pico de Fluxo Inspiratório Nasal (PFIN) e valores da escala Nasal Obstruction Symptom Evaluation (NOSE). A postura corporal foi avaliada com medidas biofotogramétricas (Software SAPO, v.0.68) como: Distância Cervical (DC); Alinhamento Horizontal da Cabeça (AHC); Ângulo de Flexo-Extensão da Cabeça (FE) e Distância Lombar (DL). Para a análise dos dados foram utilizados os testes U de Mann-Whitney, Kruskal-Wallis, Correlação de Spearmann e Regressão Logística Múltipla. PFIN e %PFIN foram menores nas crianças com sono agitado (p=0,006 e p=0,002), relato de obstrução nasal (p=0,027 e p=0,023), rinorreia (p=0,004 e p=0,012), fechamento labial assistemático na mastigação (p=0,040 e p=0,026), velocidade mastigatória reduzida (p=0,006 e p= 0,008), com alteração na deglutição de sólidos (p=0,006 e p=0,001) e somente PFIN naquelas com largura de palato reduzida (p=0,037) e alteração da fala (p=0,004). Foram encontrados valores menores de PFIN nas crianças com palidez das conchas nasais inferiores (p=0,040). PFIN e %PFIN foram maiores nas crianças com lábio levemente evertido (p=0,008 e p=0,000) e somente o PFIN naquelas com largura aumentada da língua (p=0,027). FE foi maior nas crianças com permeabilidade nasal diminuída (p=0,023). Foi encontrada correlação negativa e fraca entre FE e %PFIN (r=-0,266; p=0,002) e positiva e fraca entre DC e PFIN (r=0,209; p=0,016). Os escores da escala NOSE foram negativamente correlacionados com PFIN (r= -0,179; p=0,039). Foi observada associação do diagnóstico de respiração com: relato de obstrução nasal (OR =5,55), tempo de uso de chupeta (OR=1,25), tipo facial convexo (OR=3,78), ângulo nasolabial obtuso (OR=4,30), postura de lábios entreabertos ou abertos (OR=4,13), postura de língua no assoalho da boca (OR=5,88), largura do palato duro reduzida (OR=2,99), contrações não esperadas dos músculos orbiculares e mentual durante a mastigação (OR= 2,97), tonsilas faríngeas obstrutivas (OR=8,37), má oclusão classe II de Angle (OR= 10,85) e conservação gengival regular (OR=2,89). A permeabilidade nasal foi menor em crianças com sono agitado, sinais e sintomas de rinite, largura reduzida do palato duro e alterações nas funções de mastigação, deglutição e fala. Crianças com permeabilidade nasal reduzida apresentaram maior extensão da cabeça e esta alteração postural tende a aumentar à medida que o fluxo nasal diminui, indicando uma relação entre a postura craniocervical e permeabilidade nasal. Foram associadas com a RO as variáveis: relato de obstrução nasal; tempo de uso de chupeta; tipo facial convexo; ângulo nasolabial obtuso; postura de lábios entreabertos ou abertos; postura de língua no assoalho da boca; largura reduzida do palato duro; contrações não esperadas na mastigação; tonsilas faríngeas obstrutivas, má oclusão classe II de Angle e conservação gengival regular.

This work aims to investigate, from the perspective of the Acoustic Theory of Speech Production, the occurrence of palatalization of alveolar nasal from the analysis of speech data of three women born in União dos Palmares. Considering that most of the studies on palatalization in Brazil are devoted to analyzing the stops / t, d /, this study has its relevance, since it is dedicated to another segment susceptible to this process. The data was analyzed using the PRAAT computational application to describe the visual parameters in order to describe the visual parameters from the observation of the trajectory of the formants in the spectrum that can be interpreted as a lane for the point of articulation. In addition, using the R program package, we analyzed if are difference in distribution of values of frequencies of F1, F2 e F3 and we observe the interference of adjacent contexts to the alveolar nasal in the palatalization process. The results indicated the occurrence of three variants, namely: [n], [nʲ] and [ɲ]. The distinction of the variants was obtained from the observation of the frequency relation of F2 and the other frequencies, as the more the tongue approaches the palatal region, the more F2 increases. As for the influence of the phonetic environment, the upper segments seem to favor the process. / FAPEAL - Fundação de Amparo à Pesquisa do Estado de Alagoas / Este estudo tem por objetivo investigar, sob a perspectiva da Teoria Acústica da Produção da Fala, a ocorrência de palatalização da nasal alveolar a partir da análise de dados de fala de três mulheres nascidas em União dos Palmares. Considerando que grande parte dos estudos sobre palatalização no Brasil se dedica a analisar as oclusivas /t, d/, este estudo tem sua relevância, pois se dedica a outro segmento suscetível a esse processo. Os dados são analisados utilizando o aplicativo computacional PRAAT de modo a descrever os parâmetros visuais a partir da observação da trajetória dos formantes no espectro que são interpretados como pista para o ponto de articulação. Além disso, utilizando o pacote de programas R, analisamos se há diferença na distribuição dos valores das frequências de F1, F2 e F3 e observamos a interferência dos contextos adjacentes à nasal alveolar no processo de palatalização. Os resultados apontam a ocorrência de três variantes, a saber: [n], [nʲ] e [ɲ]. A distinção das variantes se deu a partir da observação da relação da frequência de F2 e as demais frequências de modo que quanto mais a língua se aproxima da região palatal, mais F2 aumenta. Quanto à influência do ambiente fonético, os segmentos altos parecem favorecer o processo.

O habitat natural da Neisseria meningitis é a nasofaringe humana e a transmissão da bactéria é por contato direto ou por inalação de partículas durante a fase de transmissão N. meningitis é uma bactéria Gram-negativa responsável por uma significante mortalidade em todo o mundo. Embora existam vacinas polissacárides contras os sorogrupos A, C, W135 e Y , não há uma vacina adequada para crianças menores de 4 anos para o sorogrupo B. Estudos estão sendo direcionadas para pesquisa de antígenos vacinais que são derivados da proteínas de membrana externa(NOMV). Entretanto vacinas baseadas em NOMV são consideradas pouco imunogênicas , fazendo com que o uso de adjuvantes seja necessário. Este estudo investiga a imunogenicidade da NOMV de N. meningitidis administrada pela via intranasal/intramuscular em camundongos neonatos BALC/c, usando proteína de membrana externa (NOMC) obtido de uma cepa epidêmica de N. meningitidis B:4:P1:15. As cepas usadas para imunização dos camundongos foram selecionadas por colony-blot, usando anticorpo monoclonal anti L3,7,9 para maior expressão do LPS contra o imunotipo L3,7,9 presente na cepa (B:4:P1:15 3,7,9). Como adjuvantes de mucosa foram utilizados Bordetella pertussis (células íntegras) ou sobrenadante de cultura com 48 horas ou hidróxido de alumínio [Al(OH)3]. O soro dos camundongos imunizados foram analisados pelo método de ELISA à fim de se comparar os diferentes adjuvantes utilisados. O índice de avidez também foi determinado. IgG e IgM foram detectados nos soros dos camundongos após imunização, com índices de intermediária e alta avidez. Todos os adjuvantes foram capazes de aumentar a resposta imune contra NOMV de N.meningitidis. A via intranasal foi adequada para sensibilizar as células do sistema imune que foram rapidamente estimuladas pela via intramuscular usando os adjuvantes utilizados na presente investigação. Dados sugerem que o estudo da NOMV é importante na indução da imunidade de mucosa para N. meningitidis B, e que a qualidade e magnitude da resposta imune gerada pelas vacinas de mucosa são influenciadas tanto pelo adjuvante como pelo antígeno. Concluímos que NOMV juntamente com adjuvantes de mucosa tem considerável potencial no desenvolvimento de vacinas contra o meningococo do sorogrupo B. / The natural habitat of Neisseria meningitidis is the human nasopharynx, and the bacterium is transmitted by direct mouth-to-mouth contact or by the inhalation of released mucous particles during close contact. N meningitidis is a Gram-negative bacterium responsible for significant mortality worldwide. While effective polysaccharide-based vaccines exist against serogroups A, C, W135, and Y, no similar vaccine is suitable for children under 4 years against disease caused by serogroup B strains. Current studies are searching for vaccinal antigens that are derived from the native outer membrane (NOMV). However, vaccines based on NOMV are considered weak, making the use of adjuvants necessary. This study investigated the immunogenicity of NOMV of N. meningitidis administered intranasal/intramuscular in neonate BALB/c mice, using the native outer membrane complex (NOMC) obtained from an epidemic strain of N. meningitidis B:4:P1.15. The strains used for immunization of mice were selected by colony-blot, using anti L3,7,9 monoclonal antibodies, for the highest expression of LPS among the immunotypes (B:4:P1:15 L9á). As mucosal adjuvants, we used Bordetella pertussis (whole cells) or the supernatant of 48 h culture of this bacterium, followed by an intramuscular dose of the same protein adsorbed onto , B. pertussis (whole cells) or 48-h B. pertussis culture supernatant or aluminum hydroxide [Al(OH)3]. Sera of immunized mice were evaluated by ELISA in order to compare the different adjuvants used. We also determined their avidity index. IgG and IgM were detected in the serum of mice after immunization, with avidity indices that ranged from intermediate to high. All adjuvants were capable of increasing the immune response against NOMV of N. meningitidis in the homologous prime/boost schedule used. The intranasal route was suitable for sensitizing the cells of the immune system which were quickly stimulated by the intramuscular route using the adjuvants analysed in the present invertigation. Data suggest that the NOMV studied is important in the induction of mucosal immunity to N. meningitidis B, and that the quality and magnitude of the immune responses generated by mucosal vaccines are influenced by the adjuvant as well as the antigen. In conclusion, nasal delivery of NoMV with mucosal adjuvants has considerable potential in the development of a mucosal vaccine against serogroup B meningococci.

The runic alphabet in the Viking Age (ca. 800-1100) only consisted of 16 characters. These did not cover the Rune-Swedish phoneme system. One of the runes, the so-called os-rune, was used for at least 8 different phonemes. By tradition it has been used to date Viking Age runic inscriptions in the Scandinavian countries. The present work investigates the phonetic and phonemic value of the os-rune in Rune-Swedish inscriptions on stone, altogether 1,745 instances in 961 inscriptions. On the basis of the analysis, the accepted view of the chronological value of the os-rune is assessed, and is found to be non-valid. The regional variations in the use of the os-rune are also studied, particularly in the context of individual rune-carvers, but also to see if any dialectal variation is discernable. It is found that there is a marked consistency in the use of the os-rune for either rounded or unrounded vowels. Inscriptions, where both uses occur, are concentrated to one small geographical area. There are also areas, where the use of the os-rune for rounded vowels is the rule. / <p>Digitaliserad utgåva 2016, kompletterad med en lista över viktigare rättelser</p> / De vikingatida runinskrifternas kronologi

Climate has a selective influence on nasal cavity morphology. Due to the constraints of cranial integration, naturally selected changes in one structure necessitate changes in others in order to maintain structural and functional cohesion. The relationships between climate and skull/nasal cavity morphology have been explored, but the integrative role of nasal variability within the skull as a whole has not. This thesis presents two hypotheses: 1) patterns of craniofacial integration observed in 2D can be reproduced using 3D geometric morphometric techniques; 2) the nasal cavity exhibits a higher level of covariation with the lateral cranial base than with other parts of the skull, since differences in nasal morphology and basicranial breadth have both been linked to climatic variables. The results support the former hypothesis, but not the latter; covariation observed between the nasal cavity and other cranial modules may suggest that these relationships are characterized by a unique integrative relationship. / February 2016

Over the past couple of years there has been rapid progress in the development and design of safe and effective delivery systems for the administration of protein and peptide drugs. The effective delivery of these type of drugs are not always as simple as one may think, due to various inherent characteristics of these compounds. Due to the hydrophilic nature and molecular size of peptide and protein drugs, such as recombinant human growth hormone, they are poorly absorbed across mucosal epithelia, both transcellularly and paracellularly. This problem can be overcome by the inclusion of absorption enhancers in peptide and protein drug formulations but this is not necessarily the best method to follow. This investigation focussed specifically on the evaluation of the ability of the PheroidTM carrier system to transport recombinant human growth hormone across mucosal epithelia especially when administered via the nasal cavity. The PheroidTM delivery system is a patented system consisting of a unique submicron emulsion type formulation. The PheroidTM delivery system, based on PheroidTM technology, will for ease of reading be called Pheroid(s) only throughout the rest of this dissertation. The Pheroid carrier system is a unique microcolloidal drug delivery system. A Pheroid is a stable structure within a novel therapeutic system which can be manipulated in terms of morphology, structure, size and function. Pheroids consist mainly of plant and essential fatty acids and can entrap, transport and deliver pharmacologically active compounds and other useful substances to the desired site of action. The specific objectives of this study can be summarised as follows: a literature study on Pheroid technology; a literature study on chitosan and N-trimethyl chitosan chloride; a literature study on recombinant human growth hormone (somatropin); a literature study on nasal drug administration; formulation of a suitable Pheroid carrier; entrapment of somatropin in the Pheroid carrier, and in vivo evaluation of nasal absorption of somatropin in Sprague-Dawley rats. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Une des données essentielles que recherche le clinicien ORL lors de son diagnostic concerne la fonctionnalité des fosses nasales. Dans certains cas, cette fonction n’est approchée que de manière partielle par les diverses méthodes de mesures mises à sa disposition. La prévalence des obstructions nasales chroniques dans la population générale1 (30% de la population) souligne l’intérêt que les orthodontistes doivent porter aux pathologies respiratoires. L’acquisition d’un outil de diagnostic fiable de l’obstruction nasale permettra d’effectuer un traitement plus précoce afin de guider au mieux la croissance crânio-faciale. La RAA ne peut pas être actuellement utilisée comme unique examen diagnostique, car sa corrélation avec les évaluations subjectives peut rester faible. L’objectif de ce travail est de fournir un modèle d’aide au diagnostic de l’obstruction nasale pour tous les patients. Dans les cas où la RAA ne permet pas un diagnostic certain de l’obstruction nasale, la simulation numérique permettrait, après avoir identifié les situations anatomiques particulières, d’obtenir une approche fonctionnelle objective en confirmant ou non le diagnostic de la RAA. La méthode utilisée pour ce travail de thèse consiste en une résolution complète des équations de Navier-Stokes dans des géométries reconstruites en 3D, c’est-à-dire ayant bénéficié d’un traitement numérique pour extraire les contours puis créer les maillages surfaciques et volumiques. Le développement d'outils de mesure objectifs est un enjeu capital pour déterminer les stratégies thérapeutiques optimales et pour évaluer les résultats des traitements. La modélisation par ordinateur de la dynamique des flux aériens au sein des fosses nasales à partir de reconstructions tomodensitométriques tridimensionnelles peut présenter des applications cliniques. Une de ses applications permettrait à l’ORL de visualiser l’écoulement post-opératoire virtuellement. / One of the essential data sought by the clinician in his diagnosis on the functionality of the nasal cavity. In some cases, this function is only partially approached by various measurement methods at its disposal. The prevalence of chronic nasal obstruction in the population (30% of the population) underlines the interest to orthodontists must wear respiratory disorders. The acquisition of a reliable diagnostic tool of nasal obstruction will allow for earlier treatment to guide the best craniofacial growth. The RAA can not be currently used as single diagnostic test, because its correlation with subjective assessments can remain low. The objective of this work is to provide a model for the diagnosis of nasal obstruction for all patients. In cases where the RAA does not allow a definite diagnosis of nasal obstruction, numerical simulations allow, after identifying the particular anatomical situations, to obtain a functional objective or not confirming the diagnosis of rheumatic fever. The methodology for this thesis consists of a complete resolution of the Navier-Stokes equations in geometries reconstructed in 3D, that is to say who received a digital processing to extract the contours and surface meshes and create volume. The development of objective measurement tools is a key issue in determining optimal treatment strategies and to evaluate treatment outcomes. Computer modeling of the dynamics of air flow within the nasal cavity from three-dimensional CT reconstructions may have clinical applications. One of its applications allow to visualize the flow postoperative virtually.

Este trabalho teve por objetivo analisar o papel da frequência lexical em dois fenômenos fonológicos variáveis que apresentam condicionamentos morfológicos, quais sejam Redução da Nasalidade e Apagamento de /r/ Final, no intuito de verificar: 1) a interação de frequência lexical com variáveis linguísticas; 2) a interação de frequência lexical com variáveis sociais; 3) o melhor modelo, se abstracionista ou exemplarista, para tratar dos resultados aqui obtidos. Para a redução da nasalidade, reanalisamos dados de Schwindt e Bopp da Silva (2010), adicionando a informação de frequência lexical para a análise dos dados; para o fenômeno de apagamento de /r/ final, novos dados foram coletados de entrevistas com informantes do Rio de Janeiro. A informação de frequência lexical dos dados foi obtida do corpus de referência ASPA (Avaliação Sonora do Português Atual). Nossos resultados apontam que frequência lexical apresenta correlação positiva com a aplicação dos fenômenos, estando condicionada à classe gramatical, não à estrutura morfológica interna da palavra. Idade apresenta uma interação bastante significativa em dados de redução da nasalidade, principalmente na classe de não verbos sem gem. A mesma interação com idade não foi encontrada no fenômeno de apagamento de /r/. Uma explicação para isso talvez esteja relacionada com a caracterização de frequência de type e frequência de token. Tendo em vista que, na análise de frequência lexical, regras relativas à morfologia interna à palavra e à fonologia parecem não ser determinantes na aplicação dos fenômenos, defendemos neste trabalho a superioridade das abordagens exemplaristas. / The purpose of this study was to analyze the role of lexical frequency in two variable phonological phenomena which present morphological conditioning, such as Nasality Reduction and Final /r/ Deletion, in order to verify: 1) lexical frequency interaction with linguistic variables ; 2) lexical frequency interaction with social variables; 3) the best model, if abstractionist or exemplarist, to deal with the results obtained here. For nasality reduction, we reanalyzed data from Schwindt and Bopp da Silva (2010), adding lexical frequency information for data analysis; for the final /r/ deletion phenomenon, new data were collected from interviews with informants from Rio de Janeiro. Lexical frequency information of the data was obtained from the reference corpus ASPA (Sound Evaluation of Current Portuguese). Our results point out that lexical frequency has positive correlation with the application of the phenomena, being conditioned by grammatical class, not by the internal morphological structure of the word. Age has a very significant interaction in nasality reduction data, especially in the class of non-verbs without gem. The same interaction with age was not found in the final /r/ deletion phenomenon. An explanation for this may be related to the characterization of type and token frequency. In lexical frequency analysis, considering that rules regarding the internal morphology of words and regarding phonology do not seem to be decisive in the application of both phenomena, we argue for the superiority of the exemplarist approaches.