In experimental models of demyelination such as cat optic nerve injected with antibody to galactocerebroside, stepwise and ultimately full repair occurs, starting with recruitment of oligodendrocyte progenitor cells (OP) from surrounding tissue and culminating in remyelination by young competent oligodendrocytes. Endogenous repair of demyelination can also occur in the adult human central nervous system, as evidenced by remyelinated shadow plaques in MS, but ultimately fails in this disease, leading to areas of chronic demyelination where surviving axons are both dysfunctional in terms of conduction and vulnerable to ongoing damage. In order to meaningfully investigate this failure of remyelination in the human situation, an essential prerequisite is to be able to reliably identify the neuroglial cells, and in particular, oligodendrocyte lineage cells, involved in the repair pathway in situ in post mortem tissue. While some marker antigens have been shown to remain demonstrable despite autolytic change and through differing fixation levels, others are far more sensitive and only reliable in freshly obtained tissue with light fixation. For instance, the surface antigens NG2 and PDGFαR, which have been widely used in experimental studies as a marker for OP both in vivo and in vitro, have been shown to be adversely affected by both fixation and autolysis. To this end, the cat optic nerve demyelination model, in which the reparative oligodendrocyte lineage stages have been antigenically defined, was extended to normal optic nerve including lightly fixed tissue. Here, NG2, PDGFαR and the oligodendrocyte lineage transcription factors Olig1 and Olig2 were able to be demonstrated and then correlated with the existing antigenic phenotypes. Subsequently, normal human optic nerve, optimised for both morphological preservation and antigen retention, was used to develop an in vivo staining profile for all neuroglia including OP, that was then applied to conventionally prepared, normal and MS tissue. It was found that, with careful attention to technical parameters such as post mortem interval and details of fixation, OP and other stages of the remyelinating oligodendrocyte lineage could be identified in such material, resulting in meaningful insight into the repair status of the three MS samples studied.

Diss. (sammanfattning) Linköping : Univ. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (M.S.P.H.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 58 pages. Includes bibliographical references.

No description available.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Mouth breathing is frequently associated to growth alterations and to the oral facial structures development, as well as head position alterations. However, it is manifested a lack of studies able to relate the disorders in the craniofacial morphology to the mouth breathing etiology. In this sense, this study aimed to verify the possible craniofacial morphology differences between nasal breathing and mouth breathing children of obstructive and vicious etiology, through the application of oral facial anthropometric and head posture evaluation. The sample consisted of 62 leukoderms children at ages between 7 years and 11 years and 11 months old. It was carried out a speech-language selection and otolaryngologist evaluation, followed by a nasal fibroscopy, leading to the participants classification into three groups: nasal breathers, mouth obstructive breathers and mouth vicious breathers. An oral facial anthropometric evaluation took place in order to determine the oral facial measurements and proportions and the participants facial type; and the computerized photogrammetric evaluation, followed by a physical examination in order to verify the head position related to the horizontal. The data were descriptively and statistically analyzed at the significance level of 5%. The comparisons among the groups were done through the ANOVA variance analysis and the Kruskal-Wallis test; the association between the variants was verified through the chi-square independence test and the residual analysis of the chi-square; and the correlation analyses was done by the Spearman s rank coefficient. The anthropometric measurements and the oral facial proportions, as well as the head position, were similar in the three groups. There was an association between the facial type and the breathing mode/mouth breathing etiology. The significant associations were braquifacial in the nasal breathers group and also in the obstructive mouth breathers. A correlation between facial type and head position was not verified. In this sense, it can be concluded, by the present study, that nasal and obstructive mouth breathers of obstructive and vicious etiology do not present differences concerning the studied craniofacial morphology aspects, except for to the facial type. / A respiração oral é freqüentemente associada a alterações no crescimento e desenvolvimento das estruturas orofaciais, bem como a alterações na postura da cabeça. No entanto, evidencia-se uma carência de estudos que relacionem as desordens na morfologia craniofacial à etiologia da respiração oral. Sendo assim, este estudo teve como objetivo verificar possíveis diferenças morfológicas craniofaciais entre crianças respiradoras nasais e respiradoras orais de etiologia obstrutiva e viciosa, por meio de avaliação antropométrica orofacial e avaliação da postura da cabeça. A amostra foi composta por 62 crianças leucodermas, com idades entre 7 anos e 11 anos e 11 meses. Foram realizadas triagem fonoaudiológica, avaliação otorrinolaringológica e exame de nasofibrofaringoscopia, que possibilitaram a classificação dos participantes em três grupos: respiradores nasais, respiradores orais obstrutivos e respiradores orais viciosos. Realizou-se avaliação antropométrica orofacial para determinar as medidas e proporções orofaciais e o tipo facial dos participantes e avaliação fotogramétrica computadorizada, seguida de exame físico postural, para verificar a postura da cabeça em relação ao plano horizontal. Os dados foram analisados descritivamente e estatisticamente ao nível de significância de 5%. As comparações entre grupos foram realizadas por meio da análise de variância de ANOVA e do teste de Kruskal- Wallis; a associação entre variáveis foi verificada através do teste de independência do qui-quadrado e da análise de resíduos do qui-quadrado; a análise de correlação foi realizada com o coeficiente de correlação de Spearman. Verificou-se que as medidas antropométricas e proporções orofaciais, assim como a postura da cabeça apresentaram-se semelhantes nos três grupos. Houve associação entre o tipo facial e o modo respiratório/ etiologia da respiração oral. As associações significantes foram do tipo braquifacial com o grupo de respiradores nasais e de respiradores orais obstrutivos. Não foi verificada correlação entre tipo facial e postura da cabeça. Deste modo, concluiu-se que, no presente estudo, os respiradores nasais e orais de etiologia obstrutiva e viciosa não apresentaram diferenças nos aspectos da morfologia craniofacial investigados, exceto o tipo facial.

No description available.

Introdução: O câncer de mama tem se mostrado a neoplasia mais incidente entre as mulheres de todo o mundo. Entretanto, percebe-se que a incidência apresenta grande variação geográfica, sugerindo que a ação dos fatores de risco varie acentuadamente entre as diferentes populações. Assim, estudos em determinadas populações sobre os seus fatores determinantes para câncer de mama podem contribuir para melhorar as estratégias de saúde pública, reduzindo sua morbi-mortalidade. Objetivo: Avaliar potenciais fatores de risco para câncer de mama em uma população de Porto Alegre e construir um modelo multivariado com estes fatores para predição de risco de câncer de mama. Delineamento: Estudo de coorte de base populacional. Método: Foram selecionadas 4.242 mulheres com idades entre 40 e 69 anos, sem história pregressa de câncer de mama, em atendimento em unidades básicas de saúde de Porto Alegre, as quais foram submetidas a rastreamento mamográfico. Elas foram avaliadas em relação aos seguintes fatores de risco: raça, tabagismo, etilismo, idade da menarca, idade do nascimento do primeiro filho, número de gestações, idade da última gestação, tempo de amamentação, história de ooforectomia e histerectomia, idade da menopausa, tempo de uso de reposição hormonal, uso de contraceptivo hormonal, histórico de biópsias mamárias, história familiar, peso e altura. A coleta de dados referente aos potenciais fatores de risco para câncer de mama foi realizada em dois momentos distintos, sendo a primeira coleta realizada durante o período de recrutamento das participantes compreendido entre os anos de 2004 e 2006 nas unidades básicas de saúde e a segunda coleta de dados foi realizada no momento em que as participantes compareciam ao centro de referência para a primeira visita de rastreamento mamográfico. As variáveis coletadas em ambos os momentos eram complementares, porém algumas variáveis estavam presentes em ambos os instrumentos de coleta de dados, as quais foram analisadas apenas as variáveis coletadas no segundo momento por serem mais atuais. As variáveis categóricas foram descritas por frequências e percentuais. As variáveis quantitativas com distribuição simétrica foram descritas pela média e o desvio padrão e as variáveis com distribuição assimétrica pela mediana e o intervalo interquartil (percentis 25 e 75). A associação entre câncer de mama e potenciais fatores de risco foi avaliada através de um modelo logístico multivariado. Em todas estas análises, um valor de p abaixo de 0,05 foi considerado estatisticamente significativo e foi analisado e considerado o IC95%. Resultados: Um total de 73 participantes de 4.242 apresentaram diagnóstico de câncer de mama. A análise multivariada considerando todas as pacientes, de 40-69 anos, mostrou que quanto maior a idade (OR=1,08, 95%IC: 1,04-1,12), maior a altura (OR=1,04, 95%IC: 1,00-1,09) e história de biópsia mamária anterior (OR=2,66, 95%IC: 1,38-5,13) estavam associadas a desenvolvimento de câncer de mama. Por outro lado, o número de gestações (OR=0,87, 95%IC: 0,78-0,98) e uso de terapia de reposição hormonal (OR=0,39, 95%IC: 0,20-0,75) foram associados como fator protetor para câncer de mama. Adicionalmente, realizamos análise separando as participantes em grupos de 40-49 anos e 50-69 anos, pois algum fator de risco poderia ter comportamento específico nestas faixas etárias. Nenhum fator de risco adicional foi identificado com esta estratificação etária, sendo que alguns fatores perderam significância estatística. No grupo de 40-49 anos, altura e biópsia mamária anterior mantiveram-se como fatores de risco. No grupo de 50-69, biópsia mamária anterior manteve-se como fator de risco e número de gestações e uso de terapia de reposição hormonal mantiveram-se como fator protetor. Diversas sub-análises não contribuíram para o entendimento como reposição hormonal o qual foi identificado como fator protetor. Conclusão: Em nosso estudo o modelo de predição de risco indica que devem ser avaliadas as seguintes variáveis nesta população específica de 40 a 69 anos: idade, altura, realização de biópsias mamárias anteriores, número de gestações e utilização de terapia de reposição hormonal. Estes achados estão de acordo com a literatura e agregados a outros estudos podem ajudar a compreender melhor o modelo causal de câncer de mama na região sul do Brasil. / Introduction: Breast cancer has been the most common cancer among women worldwide. However, it is clear that the incidence has great geographic variation, which suggests that the action of risk factors varies substantially between different populations. Thus, studies on the determining factors for breast cancer in certain populations may contribute to improve public health strategies and reduce morbimortality. Objective: Assess potential risk factors for breast cancer in a population in southern Brazil and build a multivariate model using these factors for breast cancer risk prediction. Methods: 4,242 women aged between 40 and 69 years without a history of breast cancer were selected at primary healthcare facilities in Porto Alegre and submitted to mammographic screening. They were evaluated for the following risk factors: race, smoking, alcohol consumption, age at menarche, age at the birth of first child, number of pregnancies, age at the last pregnancy, duration of breastfeeding, history of oophorectomy and hysterectomy, age at menopause, duration of hormone replacement therapy, use of hormonal contraceptives, history of breast biopsies, family history, weight and height. The collection of data related to potential risk factors for breast cancer was conducted at two different times. The first collection was held during the recruitment of participants from 2004 to 2006 at primary healthcare units and the second data collection was performed at the time the participants went to the reference center for the first mammographic screening visit. The variables collected at both times were complementary, but some variables were present in both data collection instruments, and only the variables collected in the second phase were analyzed because they were more current. Categorical variables were described as frequencies and percentages. Quantitative variables with symmetric distribution were described as the mean and standard deviation, and variables with asymmetrical distribution as median and interquartile range (25th and 75th percentiles). The association between breast cancer and potential risk factors was evaluated using a multivariate logistic model. In all these analyses, a p-value less than 0.05 was considered statistically significant with a 95% CI. Results: A total of 73 participants among 4,242 had a breast cancer diagnosis. The multivariate analysis considering all patients aged 40-69 years showed that older age (OR = 1.08, 95% CI: 1.04-1.12), higher height (OR = 1.04, 95% CI: 1.00-1.09) and history of previous breast biopsy (OR = 2.66, 95% CI: 1.38 - 5.13) were associated with the development of breast cancer. Conversely, the number of pregnancies (OR = 0.87, 95% CI: 0.78-0.98) and use of hormone replacement therapy (OR = 0.39, 95% CI: 0.20 - 0 75) were associated as a protective factor for breast cancer. Additionally, we performed an analysis separating the participants into groups of 40-49 years old and 50-69 years old, since a risk factor could have a specific behavior in these age groups. No additional risk factors were identified within this age bracket, and some factors lost statistical significance. In the 40-49 year old group, height and previous breast biopsy remained as risk factors. In the 50-69 year old group, a previous breast biopsy remained as a risk factor and the number of pregnancies and use of hormone replacement therapy remained as a protective factor. A number of sub-analyses did not help us understand why or how hormone replacement acted as a protective factor. Conclusion: In our study, the risk prediction model indicates that the following variables should be assessed in this specific population from 40 to 69 years old: age, height, having had previous breast biopsies, number of pregnancies, and use of hormone replacement therapy. These findings are consistent with the literature and combined with other studies may help to better understand the causal model of breast cancer in southern Brazil.

Type 1 diabetes(T1D)is a disease that only gets more common. The etiology of the disease is not known but there are many existing theories about what the cause is. These different theories have been tested in vivoin rodents or invitro. The resultsfrom experiments done in those waysarenotall realistic because rodents differnotablyfrom humans,and when studies areperformed in vitrowith human isletsof Langerhans different hormones will accumulate. The aim of this studywas to establisha dynamic ex vivosystem in which stimulation of human islets of Langerhans can be performed in a more lifelike environment. To study islets in this system couldin the future lead to increased knowledge in the etiology of T1D.The perifusion system PERI-4.2 from Biorep Technologies together with an incubator with 37°Cand5% CO2were used to arrangethe ex vivosystem. An Insulin ELISA from Mercodia was performedto analyze the insulin secretion from the islets. Fourdifferent set ups for the system were tested and the last one showed the best results.In conclusion this study has shown that it is possible to preserve human islets of Langerhans in a dynamic ex vivosystem with a constant medium exchange if it is done under conditionswhere the islets are protected from shear forces from the supplying medium,together with a medium exchange rate which replaces the whole medium in at least one hour.