Transdermal iontophoretic delivery of ketoprofen in cadaver skin and healthy volunteers was examined. In vitro anodic and cathodic iontophoresis (0.5 mA/cm2, 3 h) of ketoprofen (75 mg/ml) resulted in equivalent intracutaneous ketoprofen permeation (232.1 ± 27.1 vs. 275.0 ± 141.0 μg/cm2, respectively), which in turn was higher than passive intracutaneous uptake of ketoprofen (40.7 ± 42.1 μg/cm2). In contrast, only cathodic iontophoresis resulted in transcutaneous ketoprofen permeation across cadaver skin, under these conditions. The in vitro study was then repeated to achieve transcutaneous permeation of ketoprofen at clinical iontophoretic parameters (0.28 mA/cm2, 40 min) by increasing drug concentration to 300 mg/ml. No stereo-selective permeation of R- and S-ketoprofen enantiomers was observed in vitro. In humans, cathodic iontophoresis of 300 mg/ml ketoprofen (0.28 mA/cm2, 40 min) was performed at the wrist. Ketoprofen was detected at 40 min (0.88 ± 0.42 μg/ml) from the forearm veins of the ipsilateral arm. Urinary excretion of ketoprofen totaled 790 ± 170 μg at 16 h post iontophoresis. This investigation is the first to clearly demonstrate transcutaneous iontophoresis of an antiinflammatory agent in humans utilizing a commercially cleared iontophoretic device. The investigation also adds to the very limited number of publications in the area of iontophoretic delivery of drugs to humans.

Osteoporosis is a common bone disease that increases risk of low-trauma fractures associated with substantial morbidity, mortality, and financial costs. Clinically, osteoporosis is defined by low bone mineral density (BMD). BMD explains approximately 60-70% of the variance in bone strength. The remainder is due to the cumulative and synergistic effects of other factors, including trabecular and cortical bone micro-architecture. In vivo quantitative characterization of trabecular bone (TB) micro-architecture with high accuracy, reproducibility, and sensitivity to bone strength will improve our understanding of bone loss mechanisms and etiologies benefitting osteoporotic diagnostics and treatment monitoring processes. The overall aim of the Ph.D. research is to design, develop and evaluate new 3-D imaging processing algorithms to characterize the quality of TB micro-architectural in terms of topology, orientation, thickness and spacing, and to move the new technology from investigational research into the clinical arena. Two algorithms regarding to this purpose were developed and validated in detail - (1) star-line-based TB thickness and marrow spacing computation algorithm, and (2) tensor scale (t-scale) based TB topology and orientation computation algorithm. The TB thickness and marrow spacing algorithm utilizes a star-line tracing technique that effectively accounts for partial voluming effects of in vivo imaging with voxel size comparable to TB thickness and also avoids the problem of digitization associated with conventional algorithms. Accuracy of the method was examined on computer-generated phantom images while the robustness of the method was evaluated on human ankle specimens in terms of stability across a wide range of resolutions, repeat scan reproducibility under in vivo condition, and correlation between thickness values computed at ex vivo and in vivo resolutions. Also, the sensitivity of the method was examined by its ability to predict bone strength of cadaveric specimens. Finally, the method was evaluated in an in vivo human study involving forty healthy young-adult volunteers and ten athletes. The t-scale based TB topology and orientation computation algorithm provides measures characterizing individual trabeculae on the continuum between perfect plate and perfect rod as well as individual trabecular orientation. Similar to the TB thickness and marrow spacing computation algorithm, accuracy was examined on computer-generated phantoms while robustness of the algorithm across ex vivo and in vivo resolution, repeat scan reproducibility, and the sensitivity to experimental mechanical bone strength were evaluated in a cadaveric ankle study. And the application of the algorithm was evaluated in a human study involving forty healthy young-adult volunteers and ten patients with SSRI treatment. Beside these two algorithms, an image thresholding algorithm based on the class uncertainty theory is developed to segment TB structure in CT images. Although the algorithm was developed for this specific application, it also works effectively for general 2-D and 3-D images. Moreover, the class uncertainty theory can be utilized as adaptive information in more sophisticated image processing algorithms such as Snakes, ASMs and graph search.

ABSTRACT External otitis and its treatment. Is a group III steroid without antibiotics sufficient therapy? – Experimental and clinical studies Per Emgård, Department of Otorhinolaryngology, University of Umeå and Ystad Hospital, Umeå and Ystad, Sweden External otitis is one of the most common ear, nose and throat (ENT) diagnoses in out-patient clinics. The clinical course of external otitis includes itching, pain, redness, swelling and effusion of the external auditory canal (EAC) with normal tympanic membrane status. The inflammatory condition is often associated with infection by bacteria, e.g. Pseudomonas aeruginosa, or skin bacteria such as Staphylococcus species. Fungi are present only in a low percentage of cases and if present Candida albicans infection is the most frequent in northern countries such as Sweden and the UK. Topical therapy is recommended in most countries and dominates the therapy in most studies. Topical drugs used are usually a combination of antibiotics and a steroid. However, external otitis is treated with surprisingly many strategies – eleven different ones in Sweden, for example, and 18 in the UK. The aims of the present studies were to – -establish an animal model, infected and uninfected, suitable for testing various treatment strategies of external otitis; and -perform a clinical study in patients to elucidate whether a group III steroid alone is as efficient for treatment of external otitis as is the commonly used topical drug containing a combination of a steroid and antibiotics. The animal model was established through mechanical irritation of the external ear canal skin of Sprague-Dawley rats. An evaluation scale for characterization of the clinical status of the ear canal was introduced, recording redness, swelling and occurrence of effusion in a standardized way. Specimens of the ear canal skin were analysed by histological techniques. A topical solution of 0.05% bethametasone dipropionate (BD) was compared with a 1% hydrocortisone solution with antibiotics oxytetracycline and polymyxin B added (HCPB), administered in the external otitis model infected or non-infected with bacteria (P. aeruginosa) and a fungus (C. albicans). The same drugs were tested in a randomized parallel-group multi-centre study in 51 patients. The clinical status of the external otitis patients was evaluated on a similar scale as used in the animal model. Early normalization of the ear canal skin status and frequency of relapses during the 6-month follow-up period were used as end-points of the study. The studies showed the following: -An animal model for external otitis, infected or uninfected, could be established. -A new scale for evaluation of the external ear canal status with regard to redness, swelling and occurrence of effusion was introduced for the animal model as well as for the investigations in patients. -Treatment with a group III steroid topical solution without antibiotics was superior to treatment with a group I steroid with antibiotics added in achieving resolution of external otitis. -The effectiveness of the topical drugs in the clinical studies in external otitis patients was similar to that in animal external otitis models. We conclude that a group III steroid solution cures external otitis more effectively than does a solution containing a group I steroid combined with antibiotics, whether infected by bacteria or by fungi. No difference was evident regarding adverse effects. Furthermore, costs favour a solution without any antibiotic components. In view of these observations a group III steroid solution is preferred for remedy of external otitis in the clinical situation. Key words: external otitis, external auditory canal (EAC), animal model, treatment, betamethasone, hydrocortisone, antibiotics, human study, Pseudomonas aeruginosa, Candida albicans.

Este trabalho de pesquisa teve por objetivo elaborar, aplicar e avaliar as contribuições de unidades de ensino potencialmente significativas (UEPS) para a aprendizagem de conteúdos sobre o corpo humano e saúde, em uma turma de 8º ano, na disciplina de ciências em uma escola municipal de Bento Gonçalves/RS. A metodologia de pesquisa segue uma abordagem qualitativa, de natureza aplicada. Quanto aos objetivos, ela é do tipo exploratória. O procedimento metodológico adotado é a pesquisa participante. A análise dos resultados utilizou os dados registrados no diário de bordo da pesquisadora, bem como os trabalhos escritos, produções artísticas e a própria fala dos alunos, os quais, ao término de cada UEPS, foram utilizados para evidenciar se a aprendizagem foi significativa. As atividades desenvolvidas visaram desafiar a transposição dos conhecimentos teóricos em diferentes linguagens que pudessem evidenciar a ocorrência da aprendizagem significativa. A diversidade de estratégias atendeu ao objetivo de realizar uma avaliação qualitativa ao longo do processo. Ao término da aplicação das UEPS, foi possível verificar que esse é um método potencialmente facilitador da aprendizagem significativa e será divulgado na forma de um guia didático, no qual todas as atividades e recursos pedagógicos serão detalhados para que outros educadores tenham acesso e possam utilizá-lo. / Submitted by Ana Guimarães Pereira (agpereir@ucs.br) on 2017-03-20T18:47:58Z No. of bitstreams: 1 Dissertacao Ariane Pegoraro Nuncio.pdf: 28738358 bytes, checksum: 7503849d406f36093683d764d2da7b3b (MD5) / Made available in DSpace on 2017-03-20T18:47:58Z (GMT). No. of bitstreams: 1 Dissertacao Ariane Pegoraro Nuncio.pdf: 28738358 bytes, checksum: 7503849d406f36093683d764d2da7b3b (MD5) Previous issue date: 2017-03-20 / This research aimed to develop, implement and evaluate the contributions of Potentially Significant Teaching Units (UEPS: Unidades de Ensino Potencialmente Significativas, acronym in Portuguese that means Potentially Significant Teaching Units) for the learning content on the human body and health, in a class of eighth school year, in science discipline in a municipal school the city of Bento Gonçalves /RS. The research methodology follows a qualitative approach applied nature. As to the objectives it is the exploratory. The methodological procedure adopted is the participant research. The analysis used the data recorded in the logbook researcher, as well as written works, artistic productions and speech own students, which at the end of each UEPS were used to show if learning was significant. The activities aimed to challenge the implementation of theoretical knowledge in different languages that could show significant learning. The diversity of strategies attended the purpose of making a qualitative assessment throughout the process. At the end of the application of UEPS, we found that this is a potentially facilitative methodology of meaningful learning and thus deserves to be disclosed in form of didactic guide, so that other educators have access to these methodologies.

Este trabalho de pesquisa teve por objetivo elaborar, aplicar e avaliar as contribuições de unidades de ensino potencialmente significativas (UEPS) para a aprendizagem de conteúdos sobre o corpo humano e saúde, em uma turma de 8º ano, na disciplina de ciências em uma escola municipal de Bento Gonçalves/RS. A metodologia de pesquisa segue uma abordagem qualitativa, de natureza aplicada. Quanto aos objetivos, ela é do tipo exploratória. O procedimento metodológico adotado é a pesquisa participante. A análise dos resultados utilizou os dados registrados no diário de bordo da pesquisadora, bem como os trabalhos escritos, produções artísticas e a própria fala dos alunos, os quais, ao término de cada UEPS, foram utilizados para evidenciar se a aprendizagem foi significativa. As atividades desenvolvidas visaram desafiar a transposição dos conhecimentos teóricos em diferentes linguagens que pudessem evidenciar a ocorrência da aprendizagem significativa. A diversidade de estratégias atendeu ao objetivo de realizar uma avaliação qualitativa ao longo do processo. Ao término da aplicação das UEPS, foi possível verificar que esse é um método potencialmente facilitador da aprendizagem significativa e será divulgado na forma de um guia didático, no qual todas as atividades e recursos pedagógicos serão detalhados para que outros educadores tenham acesso e possam utilizá-lo. / This research aimed to develop, implement and evaluate the contributions of Potentially Significant Teaching Units (UEPS: Unidades de Ensino Potencialmente Significativas, acronym in Portuguese that means Potentially Significant Teaching Units) for the learning content on the human body and health, in a class of eighth school year, in science discipline in a municipal school the city of Bento Gonçalves /RS. The research methodology follows a qualitative approach applied nature. As to the objectives it is the exploratory. The methodological procedure adopted is the participant research. The analysis used the data recorded in the logbook researcher, as well as written works, artistic productions and speech own students, which at the end of each UEPS were used to show if learning was significant. The activities aimed to challenge the implementation of theoretical knowledge in different languages that could show significant learning. The diversity of strategies attended the purpose of making a qualitative assessment throughout the process. At the end of the application of UEPS, we found that this is a potentially facilitative methodology of meaningful learning and thus deserves to be disclosed in form of didactic guide, so that other educators have access to these methodologies.