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Using the 3D shape of the nose for biometric authenticationEmambakhsh, Mehryar January 2014 (has links)
This thesis is dedicated to exploring the potential of the 3D shape of the nasal region for face recognition. In comparison to other parts of the face, the nose has a number of distinctive features that make it attractive for recognition purposes. It is relatively stable over different facial expressions, easy to detect because of its salient convexity, and difficult to be intentionally cover up without attracting suspicion. In addition compared to other facial parts, such as forehead, chin, mouth and eyes, the nose is not vulnerable to unintentional occlusions caused by scarves or hair. Prior to undertaking a thorough analysis of the discriminative features of the 3D nasal regions, an overview of denoising algorithms and their impact on the 3D face recognition algorithms is first provided. This analysis, which is one of the first to address this issue, evaluates the performance of 3D holistic algorithms when various denoising methods are applied. One important outcome of this evaluation is to determine the optimal denoising parameters in terms of the overall 3D face recognition performance. A novel algorithm is also proposed to learn the statistics of the noise generated by the 3D laser scanners and then simulate it over the face point clouds. Using this process, the denoising and 3D face recognition algorithms’ robustness over various noise powers can be quantitatively evaluated. A new algorithm is proposed to find the nose tip from various expressions and self-occluded samples. Furthermore, novel applications of the nose region to align the faces in 3D is provided through two pose correction methods. The algorithms are very consistent and robust against different expressions, partial and self-occlusions. The nose’s discriminative strength for 3D face recognition is analysed using two approaches. The first one creates its feature sets by applying nasal curves to the depth map. The second approach utilises a novel feature space, based on histograms of normal vectors to the response of the Gabor wavelets applied to the nasal region. To create the feature spaces, various triangular and spherical patches and nasal curves are employed, giving a very high class separability. A genetic algorithm (GA) based feature selector is then used to make the feature space more robust against facial expressions. The basis of both algorithms is a highly consistent and accurate nasal region landmarking, which is quantitatively evaluated and compared with previous work. The recognition ranks provide the highest identification performance ever reported for the 3D nasal region. The results are not only higher than the previous 3D nose recognition algorithms, but also better than or very close to recent results for whole 3D face recognition. The algorithms have been evaluated on three widely used 3D face datasets, FRGC, Bosphorus and UMB-DB.
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Avaliação da transportabilidade mucociliar nasal de homens e mulheres tabagistas e qualidade de diretrizes de prática clínica para doenças respiratórias crônicas /Uzeloto, Juliana Souza. January 2016 (has links)
Orientador: Ercy Mara Cipulo Ramos / Banca: Dionei Ramos / Banca: Mahara Daian Garcia Lemes Proença / Resumo: Introdução: Mulheres tabagistas apresentam maior susceptibilidade para diversas doenças, em relação ao sexo oposto. Porém não há estudos que mostrem se há diferença no comportamento do transporte mucociliar nasal entre tabagistas homens e mulheres. É certo que nem todos os tabagistas desenvolvem doenças respiratórias crônicas, no entanto, o tabagismo é considerado um importante fator de risco para essas doenças. Assim, entende-se que além de avaliar o sistema respiratório dos tabagistas, a pesquisa no desfecho da saúde do pulmão de tabagistas é essencial, já que a maioria dos pacientes atendidos na fisioterapia respiratória é doente pulmonar crônico. Objetivos: Comparar a transportabilidade mucociliar nasal de homens e mulheres tabagistas levando em consideração a idade, dados antropométricos, carga tabagística, variáveis hemodinâmicas e função pulmonar. Além de avaliar sistematicamente a qualidade de diretrizes para doenças respiratórias crônicas, relevantes para a prática da fisioterapia, por meio do instrumento AGREE II e também avaliar a confiabilidade entre os avaliadores do instrumento AGREE II. Métodos: Foram inclusos na análise um total de 70 indivíduos tabagistas (33 homens e 37 mulheres). Todos responderam a uma entrevista inicial para obtenção dos dados pessoais e carga tabagística, foram mensurados os dados antropométricos, sinais vitais e monóxido de carbono no ar exalado, além disso, foram submetidos ao teste de função pulmonar e ao teste do tempo de trânsito d... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Female smokers have increased susceptibility to various diseases in the opposite sex. But there are no studies that show if there are differences in the behavior of nasal mucociliary transport between smokers men and women. It is sure that not all smokers develop chronic respiratory diseases, however, smoking is considered a major risk factor for these diseases. Thus, it is understood that in addition to evaluating the respiratory system of smokers, research in the outcome of smokers lung health is essential, since most of the patients seen in respiratory therapy is chronic pulmonary patient. Objectives: To compare the nasal mucociliary transportability of male and female smokers taking into consideration the age, anthropometric data, smoking load, hemodynamics and lung function. In addition to systematically assess the quality of guidelines for chronic respiratory diseases relevant to the practice of physiotherapy, through the AGREE II instrument and also assess the reliability of the evaluators of the AGREE II instrument. Methods: We included in the analysis a total of 70 smokers (33 men and 37 women). All responded to an initial interview to obtain personal data and smoking load, anthropometric data were measured, vital signs and carbon monoxide in exhaled air, moreover, underwent lung function test and the saccharin transit time test (STT). For analysis of the second objective guidelines indexed in the Physiotherapy Evidence Database (PEDro) on chronic respi... (Complete abstract click electronic access below) / Mestre
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Analysis of nasal airway symmetry and pharyngeal airway following rapid maxillary expansionDiCosimo, Charles 19 June 2018 (has links)
OBJECTIVES: This retrospective cohort study tested the effect of Rapid Maxillary
Expansion (RME) on symmetrical volumetric changes in the nasal cavity. Volumetric
changes in overall nasal cavity, nasopharynx, and oropharynx were also assessed as well
as minimum cross-sectional width changes and molar angulation in association with
RME.
METHODS: CBCT scans of before and after RME treatment for 28 subjects (17 females,
11 males, average age 9.85 ± 2.42 years) were collected from a previously de-identified
database. All subjects were treated for maxillary constriction using banded hyrax
expanders. Mimics software was utilized to segment the nasal and pharyngeal airways
and create various compartments (left and right nasal cavity, nasopharynx, and
oropharynx) for volumetric analysis. Minimum cross-sectional width measurements and
maxillary first molar angulation were also assessed. Paired T-test was used to quantify
the changes brought about by expansion. Statistical significance was set at the 0.05 level.
RESULTS: Posterior expansion as measured between right and left greater palatine foramen
(GPF) averaged 2.41 mm (SD = 1.03 mm). There were statistically significant differences
in overall nasal cavity (2249.6 ± 2102.5 mm3), right nasal cavity (968.8 ± 1082.7), left
nasal cavity (1197.3 ± 1587.0), nasopharyngeal (1000.6 ± 917.7), and oropharyngeal
(2349.2 ± 2520.8) volumes. In comparing the right to left nasal cavity, no significant
changes were noted for initial volume, post-expansion volume, or pre to post-expansion
changes (T2-T1). For cross-sectional analysis, the right nasal cavity (0.13 ± 0.07 mm)
and left nasal cavity (0.11 ± 0.06 mm) showed significant increases in minimum crosssectional
width measurements. Initial maxillary molar angulation had no significant
correlation to initial nasal cavity volume on either side.
CONCLUSIONS: RME has significant benefits to increasing nasal and pharyngeal airway
cavity volumes in all segments of the airway. Nasal cavity expands symmetrically.
Minimum cross-sectional width of the left and right nasal cavities showed highly
symmetrical improvements. Initial maxillary molar angulation has no relationship to
initial nasal cavity volume.
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Associação da radiografia, tomografia computadorizada e rinoscopia no auxílio diagnóstico das afecções em cavidade nasal e seios paranasais de cães / Association of radiography, computed tomography and rhinoscopy in aid diagnosis of disorders in the nasal cavity and paranasal sinuses of dogsAuler, Fernanda de Assis Bueno 17 December 2010 (has links)
Introdução: As afecções nasais e sinonasais em cães possuem causas variadas, e algumas vezes cursam com sinusites, sendo raros os casos que não há doença nasal pré-existente. O diagnóstico presuntivo é baseado nas manifestações clínicas como secreção nasal uni ou bilateral anormais, esternutações, esternutações reversas paroxísticas, respiração estertorosa, engasgos, halitose, epistaxes, rinorragia, tosse, distrição respiratória, dor e deformação facial. Para concluir o diagnóstico, são indicados exames de imagem, rinoscopia, culturas, citologia e histopatológico. Objetivo: O presente estudo observacional teve como objetivo avaliar a contribuição ao diagnóstico das afecções da cavidade nasal e seios paranasais de cães, da radiografia, tomografia computadorizada e rinoscopia, realizando-se a comparação dos métodos diagnósticos mediante ao escore comparativo idealizado para este fim. Materiais e métodos: Foram utilizados 20 cães atendidos do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, com manifestações clínicas compatíveis com afecção nasal e submetidos a exame radiográfico, tomográfico e rinoscópico. A biópsia foi realizada, em 18 cães, por meio da rinoscopia, nos casos em que visibilizou-se proliferação tecidual, úlcera ou alteração na mucosa nasal sendo encaminhadas para estudo histológico. Resultados: Foram observados resultados estatisticamente significativos, baseados pelo escore, a radiografia em conjunto com a tomografia computadorizada, a rinoscopia associada à tomografia computadorizada e, também, a rinoscopia isoladamente, como métodos diagnósticos mais específicos na diferenciação de lesão maligna. A rinoscopia demonstrou como vantagem a visibilização direta diferenciando a presença ou não de inflamação ou proliferação tecidual, alteração anatômica, corpo estranho e placa fúngica. Conclusão: Os resultados do presente estudo indicam que embora possuam especifidade diferentes a utilização da radiografia, tomografia computadorizada e rinoscopia se complementaram como métodos diagnósticos nas afecções nasais e sinonasais dos cães avaliados. Nos casos de proliferação tecidual o estudo histológico demonstrou ser mais útil para conclusão diagnóstica em comparação aos exames de imagem e a rinoscopia. / Introduction: The nasal and sinus disorders in dogs have various causes, and sometimes go with sinusitis that there is no pre-existing nasal disease. The presumptive diagnosis is based on clinical manifestations as nasal discharge, sneezing, reverse sneezing, gagging, stertor, halitosis, epistaxis, cough, open-mouth breathing, pain and facial deformation. To complete the diagnosis, image examinations, rhinoscopy, cultures, cytology and histopathological fidings. Objectives: This observational study aimed to evaluate the contribution to the diagnosis of disorders of the nasal cavity and paranasal in dogs, radiography, computed tomography and rhinoscopy, performing comparison of diagnostic methods through the comparative score conceived for this purpose. Materials and methods: This study used 20 dogs of Veterinary Hospital of the Faculty of Veterinary Medicine and Zootechny of the University of São Paulo, with clinical signs compatible with nasal disorder and undergone radiographic examination, computed tomography and rhinoscopy. The biopsy was performed on 18 dogs through rhinoscopy, where is tissue proliferation, ulcer or change in the nasal mucosa histology study being forwarded to. Results: Significant results were observed by the score with radiography, computed tomography, rhinoscopy associated with computed tomography, and also, separately, as rhinoscopy diagnostic methods more specific differentiation of malignant lesion. The rhinoscopy demonstrated how advantage to visualize directly differentiating presence or not of inflammation or tissue proliferation, alteration, foreign body and fungal plaques. Conclusion: The results of this study indicate that although having different specific utilization, radiography, computed tomography and rhinoscopy as diagnostic methods arranged in nasal disorders of dogs and evaluated. In cases of tissue proliferation, histological study proved most useful in final diagnostic compared to the image exams and rhinoscopy.
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Concentrações de Interleucina-2 na secreção nasofaríngea de crianças acometidas de bronquiolite viral aguda pelo vírus sincicial respiratórioGiugno, Katia Maria January 2000 (has links)
Resumo não disponível.
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Contribuição da rinoscopia na avaliação de afecções nasais no cão (Canis familiaris) / Contribution of rhinoscopy in the evaluation of nasal affections in the dog (Canis familiaris)Yoshitoshi, Franz Naoki 18 June 2003 (has links)
Este trabalho teve como objetivos a avaliação da cavidade nasal, através de rinoscopia, de cães portadores de afecção nasal crônica, identificando o tipo e a localização das lesões, correlacionando-as com os achados clínicos e radiográficos; verificar a epidemiologia segundo a raça, idade, peso e sexo dos; e definir o resultado qualitativo da biópsia. Foram utilizados 38 cães com sinais clínicos e alterações radiográficas compatíveis com afecção nasal crônica. Sobre a epidemiologia das afecções nasais, tivemos maior ocorrência de cães sem raça definida (SRD), adultos, macho, de porte médio e grande. As alterações mais encontradas em cavidade nasal foram as tumorais, sendo a afecção de maior ocorrência o TVT, representado em sua maioria pelo SRD adulto e macho, seguido de neoplasia de origem mesenquimal, neoplasia de origem epitelial, pólipo, rinite crônica, corpo estranho e aspergilose. A biópsia guiada por rinoscopia foi efetiva, com exceção dos tumores de origem mesenquimal. A rinoscopia neste estudo comprovou ser um meio diagnóstico efetivo, não invasivo complementar aos exames físico e radiográfico, que permite, pela técnica anterógrada associada à retrógrada, ampla visibilização da cavidade nasal, escolha do local de biópsia e colheita de material para cultivo, e em casos de corpos estranhos permite sua remoção, servindo como método diagnóstico e terapêutico. / The aim of this study was to evaluate the nasal cavity of dogs, presented with chronic nasal disease, through rhinoscopy. In addition to checking the reliability of nasal biopsy results, rhinoscopy was used to identify the type and location of lesions and to relate them to the clinical and radiographic findings. Furthermore, we also gathered epidemiology data related to breed, age, weight and gender. For the purpose of this study we used 38 dogs that presented clinical signs and radiographic alterations compatible with chronic nasal disease. Regarding the epidemiology, the highest incidence of nasal diseases was noticed in mixed breed dogs. Also, nasal disease was more frequent in adult, male, large or medium sized dogs. The majority of nasal diseases were due to tumors, and in this regard the transmissible venereal tumor (TVT) was the most frequent and was mainly diagnosed in mixed breed, male, adult dogs. Mesenchymal neoplasia were the second most frequent alteration of the nasal cavity, followed by, epithelial neoplasia, polyps, chronic rhinitis, foreign bodies and aspergillosis. Rhinoscopy guided biopsy proved to be effective except in the case of mesenchymal tumors. The results of this study prove that rhinoscopy is an effective non-invasive diagnostic tool, which complements physical and radiological examination. Moreover, this study also shows that the association of anterior and posterior rhinoscopy techniques, allow for a wide visualization of the nasal cavity and determination of the biopsy location and collection of samples for culture. In additional, rhinoscopy is a useful tool for diagnosis and removal of foreign bodies.
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Uptake and distribution of ultrafine nanoparticles and microemulsions from the nasal mucosaBejgum, Bhanu Chander 01 July 2017 (has links)
Various colloidal delivery systems, including polymeric nanoparticles, metal colloids, liposomes, and microemulsions have been reported to enhance the delivery of therapeutic agents following intranasal administration. However, the mechanisms involved in the uptake of these nanomaterials, especially those in the ultrafine size ranges (diameter < 20 nm) through nasal mucosa and their subsequent biodistribution in the body are not well characterized. The objectives of this study address the knowledge gap regarding ultrafine nanoparticle transfer in the nasal mucosa by quantifying nanoparticle uptake and biodistibution patterns in the presence and absence of known inhibitors of endocytic processes.
The uptake of ~ 10 nm fluorescent quantum dots (QDs) was investigated by measuring the concentration of QDs following exposure to bovine respiratory and olfactory mucosal explants. An inductively coupled optical emission spectroscopy method was developed to measure the amount of QDs within the tissues. The results demonstrated that carboxylate-modified QDs (COOH-QDs) show ~2.5 fold greater accumulation in the epithelial and submucosal regions of the olfactory tissues compared to the respiratory tissues. Endocytic inhibitory studies showed that in respiratory tissues clathrin-dependent, macropinocytosis and caveolae-dependent endocytosis process were all involved in the uptake of COOH-QDs. Whereas in olfactory tissues, clathrin-dependent endocytosis was the major endocytic pathway involved in uptake of COOH-QDs. Additional energy-independent pathways appeared to also be active in the transfer of COOH-QDs into the olfactory mucosa. Interestingly, PEGylated quantum dots (PEG-QDs) of similar size ~15 nm were not internalized into the bovine nasal tissues.
In vivo fluorescence imaging was used to study the biodistribution of quantum dots following nasal instillation in mice. These studies showed that majority of COOH-QDs remain in the nasal tissues for relatively long periods of time (up to 24 h) whereas PEG-QDs showed no such accumulation. Biodistribution studies of gold nanoparticles (~15 nm) in mice using micro-CT showed that gold nanoparticles were transferred to the posterior turbinate region and a fraction of the administered dose distributed to regions in close proximity to the olfactory bulb. Both NIR imaging and micro-CT imaging were useful tools for visualization of in vivo nanoparticle distribution.
A diazepam-containing microemulsion (dispersed phase ~40 nm) was formulated to investigate the uptake mechanisms utilized for fluid-phase colloidal dispersions in the nasal mucosa. The resulting diazepam-containing microemulsion showed enhanced transfer of the drug into the bovine nasal respiratory and olfactory tissues. It is unclear if endocytosis of the fluid-phase nanodispersions played a role in drug absorption from the microemulsions in a manner similar to the uptake of solid-phase nanoparticles, however, since there was significant loss of the epithelial cell layer following exposure to the microemulsion formulation which likely altered the barrier properties of the epithelium.
These studies have increased the fundamental understanding of ultrafine nanoparticle uptake in the nasal tissues and the resulting nanoparticle biodistribution patterns. While ultrafine nanoparticles may have limited application in the development of efficient drug delivery systems, an understanding of the size-dependent and tissue-dependent processes responsible for the uptake of particulates into mucosal tissues will contribute to the rational development of nanoparticulate drug delivery strategies investigating the nasal and other routes of administration.
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Evaluation of poly D, L lactic-co-glycolic acid (PLGA) nanoparticle uptake pathways across the nasal mucosaAlbarki, Mohammed Abdulhussein Handooz 01 August 2019 (has links)
The nasal mucosa provides a non-invasive route for drug administration to the systemic circulation and potentially directly to the CNS. Nanoparticles made from biodegradable polymers, including PLGA, are of great interest for use in drug delivery systems due to their relative safety and ease of surface modification. Owing to their small size, nanoparticles may provide enhanced targeting and transport through the nasal mucosa. An improved understanding of the mechanisms and pathways of nanoparticle transfer across the nasal mucosa is needed to design effective new nasal delivery systems. This study focuses on the preparation of PLGA nanoparticles in various diameters and with varying surface characteristics followed by the in vitro investigation of the mechanisms of endocytosis and exocytosis of PLGA nanoparticles in the nasal mucosa.
PLGA nanoparticles (60 nm or 125 nm) containing the lipophilic fluorescent dye, Nile Red, were prepared using a surfactant-free nanoprecipitation method. In one investigation, the inherent negative surface charge of 60 nm PLGA nanoparticles was modified to a positive charge using a 5th generation polyamidoamine dendrimer (PAMAM) during preparation of nanoparticles. In addition, 60 nm PLGA nanoparticle surfaces were coated by adding 5 % (w/v) bovine serum albumin (BSA) to the nanoparticle dispersion and allowing protein adsorption on the particle surface. Nile Red-loaded PLGA nanoparticles were transported into the epithelial layer and reached the sub-mucosal connective tissues, yet only < 5% of the PLGA nanoparticle load was transferred into the nasal mucosa. Total uptake was size dependent, where the uptake of 60 nm unmodified PLGA nanoparticles was significantly higher than uptake of 125 nm nanoparticles. The amount of Nile Red measured in the tissues after expose to the 125 nm nanoparticles was double the amount from the 60 nm nanoparticles due to differences in the carrying capabilities of the 60 and 125 nm PLGA nanoparticles. Modification of the nanoparticle surface with PAMAM or BSA decreased the uptake of 60 nm PLGA nanoparticles into the nasal mucosa.
Endocytic mechanisms involved in the uptake of PLGA nanoparticles were studied using chemical inhibitors. Nanoparticle uptake in the nasal respiratory mucosa involved energy-dependent processes utilizing multiple known mechanisms, including clathrin-mediated endocytosis and macropinocytosis. In the olfactory mucosa, significant energy-independent nanoparticle uptake was also observed.
In order to investigate how nanoparticles exit epithelial cells for further distribution to distant tissues, the exocytosis of 60 nm Nile Red-loaded PLGA nanoparticles was evaluated using three different epithelial cell line models, RPMI-2650 (nasal), Calu-3 (lung) and MDCK-II wild type (kidney) cells. Following a 30 min exposure to a 60 nm PLGA nanoparticles dispersion, nanoparticle exocytosis into a protein-free medium was evaluated for additional 30 or 60 min. Only a limited number of NP (~ 20 % of the endocytosed NP) underwent exocytosis into the medium after 60 min, while the majority of the internalized nanoparticles remained within the cells.
The measurable transfer of PLGA nanoparticles into the nasal mucosal tissues indicates that they may be useful drug carriers for nasal administration. However, the limited exocytosis of 60 nm NP and the resulting potential for intracellular accumulation may raise toxicity concerns and result in potential cellular injury. While PLGA nanoparticles provide promising drug delivery systems for nasal administration, only with careful design of the nanoparticles, including their size and surface characteristics, will efficient and effective, safe drug delivery be accomplished.
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The ontogeny of nasal floor shape variation in Homo and the influence of facial size, the anterior dentition, and patterns of midfacial integrationNicholas, Christina Lynne 01 May 2015 (has links)
Variation in the shape and position of the internal nasal floor relative to the lower border of the piriform aperture in the genus Homo has been described as having three primary shape configurations: level, sloped, or depressed. The high frequency of depressed nasal floors among Neandertals relative to other fossil and extant groups (>80%) had originally led to the idea that nasal floor depression was related to an overall enlarged nasal capsule - an adaptive feature that would have been under selection among Neandertals living in cold, glacial climates. For a variety of reasons, subsequent research has found little empirical or theoretical support for this adaptive idea. Recent research on extant humans has also demonstrated that nasal floor shape variation, unlike many other midfacial traits, does not arise until well after birth, with nasal floor depression (when it occurs) appearing at the earliest around 3.0 years of age. Furthermore, nasal floor depression was also shown to correspond with a vertically expanded premaxillary region. Thus, it was hypothesized that nasal floor depression might be related to variation in key developmental and morphological aspects of the anterior maxillary dentition. This study metrically quantifies nasal floor topography for the first time in order to more objectively examine patterns of shape variation and to test explicit hypotheses regarding potential causative factors for nasal floor variation. The variables examined include anterior tooth dimensions, dental developmental rate, aspects of midfacial shape, overall facial size, and patterns of premaxillary/post-maxillary integration. It was found that among these, only dental developmental rate was clearly correlated with internal nasal floor shape. This result indicates that aspects of anterior dental development may indeed be a causative factor in the development of nasal floor shape variation. The existing visual discrete coding system for nasal floor topography was also evaluated in light of the new, quantitative data produced by this study as well as a critical comparison of the consistency of nasal floor topography definitions used previously in the literature. While it is suggested that quantitative data are preferable to qualitative data for this trait when possible, limitations in research methods for collecting quantitative data on osteological and fossil collections remain difficult to overcome. Thus a new, two-category presence/absence based system for describing nasal floor shape is proposed.
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Drug transporters in the nasal epithelia and their contribution in drug deliveryAl-Ghabeish, Manar I. 01 December 2014 (has links)
The nasal route has primarily been used to deliver drugs for the treatment of local diseases such as nasal infections, nasal congestion and allergies. The nasal route can also be used as a non-invasive alternative route to deliver drugs systemically when a rapid onset of action and/or avoidance of hepatic metabolism are desired. Moreover, there is a growing interest in the use of this route for direct transport of drugs from the nose to the brain. Most of the drugs that have been studied for nasal delivery are either small molecules which are lipophilic enough to passively diffuse through the nasal epithelia or macromolecules where bioavailabilities less than 1% are clinically effective and acceptable. This study focused on identifying carrier proteins or transporters in the nasal mucosa that could improve the absorption of specific drug substrates across the nasal respiratory and olfactory epithelia.
The presence of drug transporters in the nasal mucosa of humans and commonly used animal models were investigated. DNA microarray results for nasal samples from humans and two commonly used models, mice and rats, were obtained from GenBank and were analyzed in collaboration with the University of Iowa Center for Bioinformatics and Computational Biology. While cow tissues are frequently used in in-vitro nasal permeability analyses, there is limited information available in GenBank for this species. Both DNA microarray analysis and RT-PCR were performed on bovine nasal explants to determine transporter expression. Good agreement between the microarray and RT-PCR results was observed.
While human and three animal species commonly used as models in nasal drug delivery research (mouse, rat, and cow) show similar patterns of expression for several transporters, interspecies differences in the level of expression were observed. Therefore, the expression level of transporters remains a factor to consider when translating results obtained using animal models to humans.
The nucleoside transporter family was selected for further evaluation of the potential to improve the nasal absorption of substrates. Nucleoside transporters are integral proteins responsible for mediating and facilitating the flux of nucleosides across cellular membranes; they are also known to be responsible for the uptake of nucleoside analog drugs such as anti-cancer and anti-viral agents. RT-PCR and Western blotting were used to verify the presence of two transporter subtypes, ENT1 and CNT3, in the bovine nasal respiratory and olfactory mucosa. The expression level of both transporters in the respiratory mucosa was comparable to that in the olfactory mucosa. Using immunohistochemistry, ENT1 and CNT3 were found to be localized primarily at the apical surface of the nasal epithelial cells. This indicates that the nasal epithelium likely absorbs exogenous nucleosides for intracellular uses such as nucleic acid synthesis and regulating other cellular activities.
The contribution of the nucleoside transporters to the permeation of a nucleoside analogue drug, alovudine, across the nasal epithelia was also studied. The transport of alovudine showed a non-linear increase with increasing donor concentration over the range of 50 to 3000 µM which suggests that nucleoside transporters play a role in its uptake. Polarized transport was not observed suggesting that the facilitative nature of ENT1 plays a major role in alovudine transport. S-(4-nitrobenzyl)-6-thioinosine (NBMPR), an ENT1 inhibitor, incompletely decreased alovudine permeability across the nasal mucosa. This demonstrates that at least one transporter, ENT, plays a significant role in the uptake of this nucleoside drug across the nasal mucosa.
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