A review of the literature revealed that diet plays an important role in serious human noninfectious large bowel diseases including cancer and inflammatory bowel diseases. Dietary protein (especially as red and processed meats) has been implicated as a positive risk factor for colorectal cancer while starch which is not digested in the small intestine (resistant starch, RS) appears to be protective. The series of experiments described in this thesis were aimed to determine the effects of dietary proteins and RS on indices of colon health in an animal model, the laboratory rat. Genetic damage is a prerequisite for carcinogenesis and this was assessed by a specific assay (the comet assay) which gives a measure of DNA strand breaks. Loss of mucus barrier function is thought to contribute to inflammatory bowel disease by permitting bacterial translocation and this was measured optically using a microscope micrometer. Other biomarkers were measured as described below. There were four major experiments. 1. Effects of dietary red meat and casein on colonic DNA damage and interaction with resistant starch Previous studies had shown that higher dietary protein (as casein) induced genetic damage in rat colonocytes and that RS (fed as a high amylose maize starch) was protective. This study was aimed at establishing whether a high protein diet fed as cooked red meat had similar effects and whether RS was protective. Rats were fed diets containing either 15 % or 25% casein or 25% barbecued lean red beef, each with or without 48% high amylose maize starch (as a source of RS) for 4 weeks. As expected, high dietary casein caused a 2-fold increase in colonic single-strand DNA breaks compared with a low casein diet and reduced the thickness of the colonic mucus layer by 41%. High levels of cooked meat caused 26% more DNA damage than the high casein diet but reduced mucus thickness to a similar degree as casein. Addition of RS to the diet abolished the increase in DNA damage and the loss of colonic mucus thickness induced by either high protein diet. It is thought that RS promotes large bowel health through the SCFA produced by the large bowel bacteria. One acid in particular (butyrate) has been associated particularly with promotion of normal large bowel function and protection against disease. In keeping with this hypothesis, caecal and faecal short chain fatty acid pools (including those of butyrate) were increased by inclusion of RS in the diet. DNA damage is an early step in the initiation of cancer and these findings agree with the population data which suggest that total dietary protein and red meat promote risk of colorectal cancer. However, inclusion of resistant starch in the diet could significantly reduce that risk. 2. Differential effects of dietary whey, soy and casein on colonic DNA damage and interaction with resistant starch The preceding experiments showed that high levels of animal-derived proteins increased colonocyte genetic damage and loss of the mucus barrier in rats. This second experiment was designed to determine whether diets high in different types of dairy protein (casein or whey) or a plant protein isolate (soy) had similar adverse effects on colonic DNA and mucus barrier function and whether inclusion of RS in the diet was protective. Adult male Sprague Dawley rats were fed a diet containing 15 % or 25 % casein, whey or soy protein, each with or without 48 % high amylose maize starch for 4 weeks. In confirmation of the earlier studies, higher levels of dietary casein increased colonocyte DNA damage significantly. However, whey did not increase genetic damage. Colonic DNA damage was highest for soy when fed at both 15% and 25% protein in the absence of RS. Inclusion of RS in the diet attenuated colonocyte DNA damage due to higher dietary protein in all three groups. The colonic mucus barrier was thinner in rats fed higher dietary protein but the effect was reversed by feeding RS. Caecal total SCFA and butyrate pools were low in rats fed the digestible starch and were higher in rats fed RS. However, there was no relationship between caecal or faecal SCFA and genetic damage or mucus thickness. Caecal and colonic tissue weight and colon length were higher in rats fed RS, consistent with greater SCFA supply. These data confirm that higher dietary protein of animal (casein) or plant (soy) origin increases genetic damage and loss of the mucus barrier indicating that this is an effect of protein and not its source. These findings accord with the epidemiological data which link dietary protein to greater risk of colorectal cancer and inflammatory bowel disease. However, the data show also that dietary proteins differ in their specific actions on genetic damage and mucus thickness. Further, the data from the feeding of whey suggest that not all proteins are equivalent in their capacity to provoke adverse changes in colonic integrity. While the data show that RS raised large bowel and faecal SCFA, they indicate their levels were not related directly to these biomarkers. 3. Dose response effects of resistant starch on protein induced colonic DNA damage The accumulated data linking greater protein intakes to adverse changes in the colon were obtained at dietary levels which were not unreasonable in terms of animal or human consumption. However, the dietary level of RS which were fed were relatively high (48% by weight) so this study was conducted to determine its effectiveness at lower levels of dietary inclusion. It was also important to ascertain whether there was a dose-response relationship between RS intake and the observed effects. One of the mechanisms proposed for the induction of colorectal cancer by high dietary protein intakes is oxidative damage to DNA. In this experiment, this was done by assaying with endonuclease III. Adult male rats were fed a diet containing 25% casein with 0%, 10%, 20%, 30% or 40% high amylose maize starch for 4 weeks. As in the preceding studies comet tail moment was greatest and the mucus barrier thinnest in rats fed 0% RS. DNA damage was reduced and the mucus barrier thickened in a logarithmic dose-dependent manner by RS. There was no significant difference between dietary groups associated with oxidative DNA damage as measured by endonuclease III. Caecal and faecal short chain fatty acid (SCFA) pools rose with the increased level of dietary RS. DNA damage of colonocytes correlated negatively with caecal SCFA but the strongest correlation was with caecal butyrate, which is consistent with the proposed role of this SCFA in promoting a normal cell phenotype. The data show that RS prevents protein induced colonic DNA damage in a dose-dependent manner. Inclusion of 10% high amylose maize starch was found to be sufficient to oppose colonocyte DNA damage, and to increase caecal and faecal SCFA pools. Intakes of this order are not unreasonable in terms of human consumption of RS. 4. Dose response effects of red and white meat on colonic DNA damage and interaction with resistant starch The accumulated evidence from large prospective human studies links diet to colorectal cancer risk strongly. The evidence from the animal studies described in this thesis that dietary protein induces colonocyte genetic damage supports a role for high protein intakes in increasing risk. Recently, several large epidemiological studies and a meta-analysis of prospective studies have found that consumption of dietary red or processed meats, but not white (poultry) meat, is associated with increased risk of colorectal cancer. This is consistent with the data from the preceding studies that specific proteins affected colonic integrity differentially. A large prospective European study (European Prospective Investigation into Cancer and Nutrition) has reported that dietary fibre was protective. The findings reported in this thesis that RS opposes the effects of high dietary protein accord with that conclusion. This study aimed to compare the effects of cooked red (beef) or white (chicken) meat on DNA damage and mucus barrier thickness in rats. The study was designed to determine whether the relationship between the intakes of these meats was dose-dependent. Double-strand DNA breaks are thought to relate more closely to carcinogenesis than single-strand breaks so both were measured. Adult male Sprague-Dawley rats were fed a diet containing 15%, 25% or 35% cooked beef or cooked chicken each with or without 20% high amylose maize starch for four weeks. Both red and white meat increased colonic DNA damage dose-dependently. However, both single and double strand breaks were significantly greater when the rats were fed the red meat diets compared to those fed the white meat. Colonocyte DNA damage was reduced by the consumption of RS while large bowel SCFA were increased. The findings of this study are consistent with the epidemiological data which show that red meat consumption is associated with greater risk of colorectal cancer but that white meat is not. Summary The data reported in this thesis support the findings of prospective population studies that high dietary protein, red meat in particular, appears to be harmful to the health of the large bowel. However, the data demonstrate also that different protein types have differential effects on the integrity of the colonocyte DNA. Furthermore, the addition of RS to the diet protects against protein-induced colonic DNA damage and maintenance of the colonic mucus barrier, apparently through increased SCFA production by colonic fermentation. The results of these experiments indicate a strong potential for RS to be effective in maintenance of large bowel integrity in the face of high dietary protein. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1292858 / Thesis(Ph.D.)-- School of Molecular and Biomedical Science, 2007.

Made available in DSpace on 2014-06-11T19:25:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-02-29Bitstream added on 2014-06-13T20:13:51Z : No. of bitstreams: 1 carvalho_kim_me_botib.pdf: 473702 bytes, checksum: cf335e6c7efaff94811da0dd6fc60b36 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A úlcera péptica é causada por um desequilíbrio entre os fatores protetores e lesivos da mucosa. A expansão global no consumo de álcool e DAINEs têm contribuído para um aumento da incidência da doença na população. Um dos maiores problemas relativo à úlcera péptica consiste na recidiva da mesma após a terapêutica, justificando-se a busca por novos tratamentos mais eficazes. Relatos científicos mostram que os óleos essenciais derivados das plantas possuem uma variedade de atividades biológicas, tais como ansiolíticos, antioxidantes, antiinflamatórios e antiulcerogênicos. Baseando-se nessa premissa resolvemos avaliar a atividade gastroprotetora do monoterpeno geraniol. Os resultados do estudo mostraram que o geraniol na dose de 7,5 mg/Kg foi efetivo no modelo de úlcera induzida por etanol absoluto com 70% de proteção. Essa ação gastroprotetora mostrou-se dependente da presença de óxido nítrico, dos grupamentos sulfidrilas e do aumento na produção de muco gástrico. No modelo de úlcera gástrica induzida por indometacina o geraniol não teve ação antiulcerogênica, sugerindo-se que a proteção desse monoterpeno esteja associada à metabólitos da via da COX, tais como: as prostaglandinas. No modelo de úlcera induzida por etanol em ratos pré-tratados com indometacina, os resultados indicaram que a gastroproteção do geraniol está relacionada com as PGs, uma vez que na presença de um inibidor da COX, ele perdeu sua proteção. Os dados apontam ainda para uma atividade antioxidante, comprovada no modelo de isquemia e reperfusão, onde o geraniol conferiu uma proteção à mucosa gástrica de 71%, e no modelo de úlcera duodenal induzida por cisteamina cuja proteção observada foi de 68%. No modelo de ligadura de piloro observou-se a ausência de atividade antisecretória gástrica e verificou-se... / A peptic ulcer is caused by an imbalance between the protective and the agressive factors of the mucosa. The global expansion in the consumption of alcohol and NSAIDs have contributed to an increased incidence of disease in the population. One of the biggest problems relative on peptic ulcer is recurrence of it after the treatment, justifying the search for new more effective treatments. Scientific reports show that essential oils derived from plants have a variety of biological activities, such as anxiolytics, antioxidants, anti-inflammatory and antiulcerogenics. Based on this assumption we decided to evaluate the gastroprotective activity of the monoterpene geraniol. The study results showed that geraniol at a dose of 7.5 mg/Kg was effective in the model of ulcer induced by absolute ethanol with 70% protection. This gastroprotective action was dependent on the presence of nitric oxide, sulfhydryl groups (SHs) and increased production of gastric mucus. In the model of gastric ulcer indomethacin-induced geraniol (7.5 mg / kg) did not had antiulcerogenic action, suggesting that protection this monoterpene is associated with metabolites of the COX pathway, such as prostaglandins. In the model of ethanol-induced ulcer in rats pretreated with indomethacin the results indicated that the geraniol's gastroprotection is related to the prostaglandins, since in the presence of a COX inhibitor, it lost its protection. The results also point to an antioxidant activity, proven in the model of ischemia and reperfusion, where geraniol gave a protection to the gastric mucosa of 71% and the model of duodenal ulcer cysteamine-induced whose protection observed was 68%. In the pylorus ligation model was observed the absence of gastric antisecretory activity and was verified through the model of activated charcoal that this monoterpene... (Complete abstract click electronic access below)

Orientador: Clélia Akiko Hiruma-Lima / Banca: Marcos José Salvador / Banca: Luiz Claudio Di Stasi / Resumo: A úlcera péptica é causada por um desequilíbrio entre os fatores protetores e lesivos da mucosa. A expansão global no consumo de álcool e DAINEs têm contribuído para um aumento da incidência da doença na população. Um dos maiores problemas relativo à úlcera péptica consiste na recidiva da mesma após a terapêutica, justificando-se a busca por novos tratamentos mais eficazes. Relatos científicos mostram que os óleos essenciais derivados das plantas possuem uma variedade de atividades biológicas, tais como ansiolíticos, antioxidantes, antiinflamatórios e antiulcerogênicos. Baseando-se nessa premissa resolvemos avaliar a atividade gastroprotetora do monoterpeno geraniol. Os resultados do estudo mostraram que o geraniol na dose de 7,5 mg/Kg foi efetivo no modelo de úlcera induzida por etanol absoluto com 70% de proteção. Essa ação gastroprotetora mostrou-se dependente da presença de óxido nítrico, dos grupamentos sulfidrilas e do aumento na produção de muco gástrico. No modelo de úlcera gástrica induzida por indometacina o geraniol não teve ação antiulcerogênica, sugerindo-se que a proteção desse monoterpeno esteja associada à metabólitos da via da COX, tais como: as prostaglandinas. No modelo de úlcera induzida por etanol em ratos pré-tratados com indometacina, os resultados indicaram que a gastroproteção do geraniol está relacionada com as PGs, uma vez que na presença de um inibidor da COX, ele perdeu sua proteção. Os dados apontam ainda para uma atividade antioxidante, comprovada no modelo de isquemia e reperfusão, onde o geraniol conferiu uma proteção à mucosa gástrica de 71%, e no modelo de úlcera duodenal induzida por cisteamina cuja proteção observada foi de 68%. No modelo de ligadura de piloro observou-se a ausência de atividade antisecretória gástrica e verificou-se... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: A peptic ulcer is caused by an imbalance between the protective and the agressive factors of the mucosa. The global expansion in the consumption of alcohol and NSAIDs have contributed to an increased incidence of disease in the population. One of the biggest problems relative on peptic ulcer is recurrence of it after the treatment, justifying the search for new more effective treatments. Scientific reports show that essential oils derived from plants have a variety of biological activities, such as anxiolytics, antioxidants, anti-inflammatory and antiulcerogenics. Based on this assumption we decided to evaluate the gastroprotective activity of the monoterpene geraniol. The study results showed that geraniol at a dose of 7.5 mg/Kg was effective in the model of ulcer induced by absolute ethanol with 70% protection. This gastroprotective action was dependent on the presence of nitric oxide, sulfhydryl groups (SHs) and increased production of gastric mucus. In the model of gastric ulcer indomethacin-induced geraniol (7.5 mg / kg) did not had antiulcerogenic action, suggesting that protection this monoterpene is associated with metabolites of the COX pathway, such as prostaglandins. In the model of ethanol-induced ulcer in rats pretreated with indomethacin the results indicated that the geraniol's gastroprotection is related to the prostaglandins, since in the presence of a COX inhibitor, it lost its protection. The results also point to an antioxidant activity, proven in the model of ischemia and reperfusion, where geraniol gave a protection to the gastric mucosa of 71% and the model of duodenal ulcer cysteamine-induced whose protection observed was 68%. In the pylorus ligation model was observed the absence of gastric antisecretory activity and was verified through the model of activated charcoal that this monoterpene... (Complete abstract click electronic access below) / Mestre

Resumo: O presente trabalho foi delineado para investigar a freqüência de infecção pelo Helicobacter em cães oriundos do Biotério Central da UNESP - Campus de Botucatu - e a incidência da espécie Helicobacter pylori(Hp) nos animais. Os animais utilizados foram capturados em várias cidades, desconhecendo-se seus hábitos alimentares até a captura, mas é provável que foram pertencentes ou conviveram com pessoas de classe sócio-econômica de baixo poder aquisitivo, onde a incidência de Hp em seres humanos é mais elevada. Foram utilizados os métodos de teste rápido da urease, teste imunocromatográfico (kit H. pylori one step teste) e o método histoquímico de coloração pelo Giemsa. A coleta de material foi feita em 109 caninos sem raça definida, sendo 49 machos e 60 fêmeas. O sangue foi retirado da veia jugular e as amostras gástricas e duodenais foram obtidas por endoscopia (61/109) e pela técnica aberta (48/109). As análises, pelo teste rápido da urease e coloração pelo Giemsa, mostraram que, em 97,96% dos machos (48/49) e em 100% das fêmeas (60/60), foi detectada reação positiva para Helicobacter, sendo 99,08% (108/109) na totalidade dos animais. Não foram observadas alterações estatisticamente significativas entre os dois sexos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The present work was delineated to investigate the infection frequency for Helicobacter in dogs originating from Central Animal House of UNESP - Campus of Botucatu - and the incidence of the species pylori in the animals. The used animals were captured in several towns, being ignored their alimentary habits until the capture, but it is probable that they belonged or they lived together with people of socioeconomic class of low purchasing power, where the incidence of H. pylori in humans is higher. The methods used were of fast urease test, immunocromatograph test (kit H. pylori one step test) and histochemical coloration method for Giemsa. The material collection was made in 109 mongrel dogs, being 49 males and 60 females. The blood was removed of the jugular vein and the gastric and duodenal samples were obtained by endoscopy (61/109) and by the open technique (48/109). The analyses for the fast test of the urease and coloration for Giemsa showed that, in 97,96% of the males (48/49) and in 100% of the females (60/60), positive reaction was detected for Helicobacter, being 99,08% (108/109) in the totality of the animals. No statistically significant alterations significant were observed between the two sexes... (Complete abstract, click electronic address below) / Orientador: Luiz Eduardo Naresse / Coorientador: Rogério Saad Hossne / Mestre

There is no abstract available for this thesis. / Department of Family and Consumer Sciences

Made available in DSpace on 2014-11-10T11:09:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-27Bitstream added on 2014-11-10T11:57:43Z : No. of bitstreams: 1 000783736.pdf: 2035792 bytes, checksum: 625352f737e5067d881064a582a375aa (MD5) / A epidemiologia das infecções por nematódeos gastrintestinais foi avaliada em ovinos criados em Botucatu - SP. A partir de abril de 2008 até março de 2011, dois cordeiros traçadores foram expostos à infecção natural por nematódeos gastrintestinais durante 28 dias consecutivos, ao pastejar junto com um rebanho de ovelhas. Haemonchus contortus apresentou as maiores intensidades de infecção com prevalência de 100%. Não houve influência significativa das estações do ano na intensidade de infecção por H. contortus. Trichostrongylus colubriformis também apresentou prevalência de 100% com a intensidade de infecção menor durante os meses de verão. No caso de T. colubriformis, houve correlação significativa entre as contagens de vermes x precipitação (r = -0,32; P < 0,05). Outras três espécies de nematódeos foram verificadas, no entanto, em pequenas quantidades, prevalências e intensidades de infecção: Oesophagostomum columbianum 28% (25,2), Cooperia curticei 7% (4,5) e Trichuris spp. 2 % (1). Contudo, as condições ambientais da área foram favoráveis durante todo o ano para a transmissão de H. contortus e T. colubriformis. Este fato explica parcialmente o fracasso de programas governamentais e privados realizados no intuito de promover a ovinocultura no Estado, devido a taxas elevadas de mortalidade e baixa produtividade causada pela verminose / The epidemiology of gastrointestinal nematode infections was evaluated in sheep raised in Botucatu – SP. Every month, from April 2008 until March 2011, two tracer lambs were exposed to natural infection with gastrointestinal nematodes for 28 consecutive days, while grazing together with a sheep flock. Haemonchus contortus presented the highest infection intensities with 100% prevalence. There was no significant influence of the seasons in H. contortus infection intensity. Trichostrongylus colubriformis also presented 100% prevalence with the lowest infection intensity during the summer months. In the case of T. colubriformis, there was significant correlation coefficient between worm counts x precipitation (r = -0.32; P < 0.05). Other three nematodes species were found in tracer lambs, however, in small numbers. Their prevalence and mean intensity of infection (in parenthesis) were the following: Oesophagostomum columbianum 28% (25.2), Cooperia curticei 7% (4.5) and Trichuris spp. 2% (1). In conclusion, the environmental conditions of the area were very favourable for H. contortus and T. colubriformis transmission all year round. These explain in part the failure of private and governmental programs to promote the sheep breeding activity in São Paulo State due to high sheep mortality rates and low productivity caused by gastrointestinal nematode infections

Orientador: Alessandro Francisco Talamini do Amarante / Banca: Raimundo de Souza Lopes / Banca: Fernanda Rosalinski Moraes / Resumo: A epidemiologia das infecções por nematódeos gastrintestinais foi avaliada em ovinos criados em Botucatu - SP. A partir de abril de 2008 até março de 2011, dois cordeiros traçadores foram expostos à infecção natural por nematódeos gastrintestinais durante 28 dias consecutivos, ao pastejar junto com um rebanho de ovelhas. Haemonchus contortus apresentou as maiores intensidades de infecção com prevalência de 100%. Não houve influência significativa das estações do ano na intensidade de infecção por H. contortus. Trichostrongylus colubriformis também apresentou prevalência de 100% com a intensidade de infecção menor durante os meses de verão. No caso de T. colubriformis, houve correlação significativa entre as contagens de vermes x precipitação (r = -0,32; P < 0,05). Outras três espécies de nematódeos foram verificadas, no entanto, em pequenas quantidades, prevalências e intensidades de infecção: Oesophagostomum columbianum 28% (25,2), Cooperia curticei 7% (4,5) e Trichuris spp. 2 % (1). Contudo, as condições ambientais da área foram favoráveis durante todo o ano para a transmissão de H. contortus e T. colubriformis. Este fato explica parcialmente o fracasso de programas governamentais e privados realizados no intuito de promover a ovinocultura no Estado, devido a taxas elevadas de mortalidade e baixa produtividade causada pela verminose / Abstract: The epidemiology of gastrointestinal nematode infections was evaluated in sheep raised in Botucatu - SP. Every month, from April 2008 until March 2011, two tracer lambs were exposed to natural infection with gastrointestinal nematodes for 28 consecutive days, while grazing together with a sheep flock. Haemonchus contortus presented the highest infection intensities with 100% prevalence. There was no significant influence of the seasons in H. contortus infection intensity. Trichostrongylus colubriformis also presented 100% prevalence with the lowest infection intensity during the summer months. In the case of T. colubriformis, there was significant correlation coefficient between worm counts x precipitation (r = -0.32; P < 0.05). Other three nematodes species were found in tracer lambs, however, in small numbers. Their prevalence and mean intensity of infection (in parenthesis) were the following: Oesophagostomum columbianum 28% (25.2), Cooperia curticei 7% (4.5) and Trichuris spp. 2% (1). In conclusion, the environmental conditions of the area were very favourable for H. contortus and T. colubriformis transmission all year round. These explain in part the failure of private and governmental programs to promote the sheep breeding activity in São Paulo State due to high sheep mortality rates and low productivity caused by gastrointestinal nematode infections / Mestre

The combinatorial code of cPcdh isoforms creates a diversified cell-surface molecular signature for cell-cell recognition in neural networks. This genetic architecture, combined with a regulated expression pattern and trans-homophilic binding properties, provides insights into cell specialization and signaling. Anomalies in cPcdhs, which include genetic mutations, epigenetic modifications, structural variations, and altered gene expression profiles, are associated with several neurological, neuropsychiatric, and systemic conditions, highlighting the importance of cPcdh investigations. This study focuses on the transcriptional regulation of the Pcdhα gene cluster. Each neuron displays a specific Pcdhα alternate exon repertoire, necessitating an understanding of the transcriptional dynamics. Using the SK-N-SH human neuroblastoma cell line and methodologies such as cRNA-seq and Start-Seq, these dynamics are examined. The application of CRISPR-Cas9 gene editing and a dCas9-VPR gain-of-function assay in the HEK293T cell line reveals the role of as-lncRNA and its interaction with DNA methylation within the Pcdhα gene cluster. This study identifies the role of noncoding as-lncRNA in RNA transcription and provides information on CTCF binding and Pcdhα promoter activation. The research also examines the gastrointestinal domain, as cPcdhs are linked to various diseases. Shifting focus from the canonical realm of the CNS, the research embarks on a preliminary yet pivotal exploration of the gastrointestinal domain. As cPcdhs intersect with a plethora of diseases, an incisive understanding of their expression could yield revelations into tissue susceptibilities with potential disease ramifications. Employing a novel single-domain antibody technique coupled with immunohistochemistry, the endeavor casts a precise lens into the gastrointestinal expression dynamics of Pcdhα and Pcdhγ. These insights not only fortify the understanding of cPcdh within neural structures but also beckon a deeper inquiry into their multifaceted biological roles.

無線膠囊內窺鏡（CE）是一種用於檢查整個胃腸道，尤其是小腸的無創技術。它極大地改善了許多小腸疾病的診斷和管理方式，如不明原因的消化道出血，克羅恩病，小腸腫瘤，息肉綜合征等。儘管膠囊內窺鏡有很好的臨床表現，但它仍然有一定的局限性。主要問題是每次檢查產生約50,000 幅低質量的圖像，對於醫生來說，評估如此大量的圖像是一項非常耗時、耗力的工作。 / 到目前為止，對於膠囊內窺鏡的分析和評估，學者們都把膠囊內窺鏡圖像視為單獨的，獨立的觀測對象。事實並非如此，因為圖像之間往往有顯著的重疊。特別是當膠囊內窺鏡在被小腸蠕動緩緩推動時，它可以捕捉同一病灶的多個視圖。我們的研究目的是使用所有可用的資訊，包括多幅圖像，研究對於膠囊內窺鏡的電腦輔助診斷（CAD）系統。 / 在這篇論文中，我們提出了一個嵌入分類器的多類隱馬爾可夫模型（HMM）的方案，它可以融合多幅相鄰圖像的時間資訊。由於膠囊內窺鏡圖像的品質比較低，我們首先進行預處理，以加強膠囊內窺鏡圖像，增加其對比度，消除噪聲。我們調查研究了多種圖像增強的方法，並調整了它們的參數使其適用於膠囊內窺鏡圖像。 / 對於基於單幅圖像的有監督的分類，AdaBoost 作為一個集成分類器來融合多個分類器，即本論文中的支持向量機（SVM），k-近鄰（k-NN），貝葉斯分類。在分類之前，我們提取和融合了顏色，邊緣和紋理特徵。 / 對於無線膠囊內窺鏡的視頻摘要，我們提出了有監督和無監督的兩類方法。對於有監督方法，我們提出了一個基於隱馬爾可夫模型的，靈活的，可擴展的框架，用於整合膠囊內窺鏡中連續圖像的時間資訊。它可以擴展到多類別，多特徵，多狀態。我們還提出了聯合隱馬爾可夫模型和並行隱馬爾可夫（PHMM）模型對系統進行改進，它們可以被看作是決策級的資訊融合。聯合隱馬爾可夫模型通過多層次的隱馬爾可夫模型，結合不同的資訊來源，對膠囊內窺鏡視頻進行分類和視頻摘要。 並行隱馬爾可夫模型採用貝葉斯推理，在決策時融合多個不同來源的資訊。對於無監督的方法，我們首先提出了一種基於顏色的特徵提取方法。在反色顏色空間中對亮度不變的色度不變矩用來表示膠囊內窺鏡圖像的顏色特徵。接著，我們又提出了一種基於輪廓元（Contourlet）變換的局部二元模式（LBP）作為紋理特徵。在特徵空間中，我們測量了相鄰圖像的距離，並把它視為一個位於二維平面上的開放輪廓上的點。 然後，我們採用一個無參數的關鍵點檢測方法檢測在視頻片段上的突變關鍵點。基於這些突變關鍵點，我們對膠囊內窺鏡視頻進行分割。最後，在每段被分割的視頻片段上，我們通過提取有代表性的關鍵幀來實現膠囊內窺鏡視頻摘要。我們分別用模擬和真實的病人數據進行實驗，對提出的方法進行驗證，結果表明了我們所提出的方案的有效性。它在實現自動評估膠囊內窺鏡圖像上具有很大的潛力。 / Wireless Capsule Endoscopy (CE) is a non-invasive technology to inspect the whole gastrointestinal (GI) tract, especially the small intestine. It has dramatically changed the way of diagnosis and management of many diseases of the small intestine, such as obscure gastrointestinal bleeding, Crohn’s disease, small bowel tumors, polyposis syndromes, etc. Despite its promising clinical findings, it still has some limitations. The main problem is that it requires manual assessment of approximately 50,000 low quality images per examination which is highly time-consuming and labor-intense. / CE analysis and assessment so far treated CE images as individual and independent observations. It is obviously not the case as there is often significant overlap among images. In particular, CE captures multiple views of the same anatomy as the capsule is slowly propelled by peristalsis. Our broader work aims to perform computer aided diagnosis (CAD) in endoscopy using all available information, including multiple images. / In this dissertation, a framework of multi-class Hidden Markov Models (HMM) embedded with statistical classifiers for combining information from multiple CE images is proposed. Due to the low quality of CE image, pre-processing is performed to enhance CE images by increasing the contrast and removing noises. Several image enhancement methods are investigated and customized for CE images. For frame-based supervised classification, AdaBoost is used as the ensemble classifier to combine multiple classifiers, i.e. support vector machine (SVM), k-nearest neighbor (k-NN), and Bayes classifier. Before classification, color, edge and texture features are extracted and fused. Finally, both supervised and unsupervised methods are proposed for CE study synopsis. For supervised method, a flexible and extensible framework based on HMM is developed to integrate temporal information in CE images. It can be extended to multi-class, multi-features, and multi-states. Improvements can be made by combined HMM and Parallel HMM (PHMM) which are introduced as decision-level fusion schemes. Combined HMM considers different sources via a multi-layer HMM model to perform classification and video synopsis. PHMM employs Bayesian inference to combine the recognition results at decision level. For unsupervised method, illumination-independent opponent color moment invariants and local binary pattern (LBP) based on Contourlet transform are explored as color and texture features, respectively. Pair-wise image dissimilarity is measured in the feature space and treated as points on an open contour in a 2-D plane. CE video is segmented based on sudden change points which are detected using a non-parametric key-point detection method. From each segment, representative frames are extracted to summarize the CE video. Validation results on simulated and real patient data show promising performance of the proposed framework. It has great potential to achieve automatic assessment for CE images. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Zhao, Qian. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 142-175). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Abstract --- p.ii / Acknowledgments --- p.vii / List of Tables --- p.xiii / List of Figures --- p.xv / Chapter 1 --- The Relevance of Synopsis --- p.1 / Chapter 1.1 --- Problem Statement --- p.1 / Chapter 1.2 --- Application - Capsule Endoscopy Assessment --- p.4 / Chapter 1.3 --- Literature Review --- p.9 / Chapter 1.3.1 --- Methods Based on Frame Classification --- p.11 / Chapter 1.3.2 --- Methods Integrating Temporal Information --- p.14 / Chapter 1.4 --- Contributions --- p.19 / Chapter 1.5 --- Organization --- p.23 / Chapter 2 --- Preliminary --- p.25 / Chapter 2.1 --- Hidden Markov Model (HMM) --- p.25 / Chapter 2.2 --- Factorial HMM --- p.35 / Chapter 3 --- Temporal Integration in Capsule Endoscopy Image Analysis --- p.37 / Chapter 3.1 --- Pre-processing --- p.38 / Chapter 3.2 --- Feature Extraction --- p.43 / Chapter 3.3 --- Frame-based Supervised Classification --- p.47 / Chapter 3.3.1 --- Supervised Classification using Individual Frames --- p.47 / Chapter 3.3.2 --- Ensemble Learning Based on AdaBoost --- p.50 / Chapter 3.4 --- Sequence-based Supervised Classification --- p.52 / Chapter 3.5 --- Experiments --- p.58 / Chapter 3.5.1 --- Capsule Endoscopy Image Enhancement --- p.60 / Chapter 3.5.2 --- Frame-based Supervised Classification --- p.67 / Chapter 3.5.3 --- Image Sequence Classification --- p.68 / Chapter 3.6 --- Discussion --- p.80 / Chapter 3.7 --- Summary --- p.82 / Chapter 4 --- Capsule Endoscopy Study Synopsis --- p.98 / Chapter 4.1 --- Supervised Synopsis Using Statistical Models --- p.98 / Chapter 4.2 --- Unsupervised Synopsis via Representative Frame Extraction --- p.100 / Chapter 4.2.1 --- Feature Extraction --- p.100 / Chapter 4.2.2 --- Non-parametric Key-point Detection --- p.111 / Chapter 4.2.3 --- Representative Frame Extraction --- p.112 / Chapter 4.3 --- Experiments --- p.119 / Chapter 4.3.1 --- Supervised Synopsis Based on HMM --- p.119 / Chapter 4.3.2 --- Unsupervised Synopsis --- p.125 / Chapter 4.4 --- Discussion --- p.132 / Chapter 4.5 --- Summary --- p.133 / Chapter 5 --- Conclusions and Future Work --- p.138 / Chapter 5.1 --- Conclusions --- p.138 / Chapter 5.2 --- Future Work --- p.141 / Bibliography --- p.142

Among all the major infectious human diseases, gastro-intestinal infections caused by microbial pathogens are a major cause of morbidity and infant death in developing countries, largely due to inadequate sewage disposal and contaminated water. Traditional health practitioners in South Africa play a crucial role in providing health care to the majority of the population. Many plants are locally used by South African traditional healers to treat microbial infections related to gastro-intestinal tracts. Ethnopharmacological and ethnobotanical studies using traditional knowledge as a selection strategy has given priority to certain plants for isolation and identification of plant novel bioactive compounds. Pharmacological and phytochemical studies of the investigated twelve medicinal plant species (from 10 families) extensively used as antimicrobials against gastro-intestinal infections was necessary to validate the use of the plants. Furthermore, to provide sufficient preliminary information for the isolation and identification of active compounds that are present in the investigated plants. Plant parts were sequentially extracted using petroleum ether (PE), dichloromethane (DCM) and 70% ethanol (EtOH). Cold water and boiled (decoction) extracts of the plant materials were prepared non- sequentially. Among the extracts, EtOH yielded the highest amount of plant substances. A total number of 85 extracts were evaluated for antibacterial activity, 80 for antifungal activity, 64 for anti-inflammatory activity, and 27 biologically active extracts were tested for genotoxicity. The microdilution method was used to determine the minimum inhibitory concentration values in the antibacterial assay against two Gram-negative bacteria (Escherichia coli ATCC 11775 and Klebsiella pneumoniae ATCC 13883) and two Gram-positive bacteria (Bacillus subtilis ATCC 6051 and Staphylococcus aureus ATCC 12600). A modified microdilution method was used to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values in the antifungal assay against Candida albicans. Cyclooxygenase assay was used to evaluate the anti-inflammatory activity of the extracts against cyclooxygenase-1 and -2 (COX-1 and COX-2) enzymes. The plant extracts were screened first at a concentration of 250 ƒÊg/ml per test sample, and then further screened at concentrations of 125 and 62.5 ƒÊg/ml for extracts that inhibited the COX-2 enzyme. The Ames test was used to test for genotoxicity in extracts that showed interesting pharmacological activities using Salmonella typhimurium strain TA98. Among the screened extracts, 25 extracts showed good antibacterial activity with MIC values . 1.0 mg/ml. Dichloromethane extracts exhibited the greatest antibacterial activity, and Gram-positive bacteria were most susceptible. The best antibacterial activity was exhibited by Becium obovatum leaf EtOH extracts with an MIC value of 0.074 mg/ml. A broad spectrum antibacterial activity was observed by leaf extracts of Cucumis hirsutus (PE), Haworthia limifolia (PE), Protea simplex (PE and DCM) and Dissotis princeps (EtOH) against both Gram-negative and Gram-positive bacteria. No interesting antibacterial activity was exhibited by water extracts with the exception of Dissotis princeps water extract with a good antibacterial activity against Gram-positive and Gram-negative bacteria. In the antifungal assay, 6 extracts showed interesting antifungal activity. Protea simplex leaf PE extract showed the best fungicidal activity with an MFC value of 0.014 mg/ml. The best overall antifungal activity was observed in plant EtOH extracts. Some extracts from Agapanthus campanulatus (leaves and roots), Dissotis princeps (leaves), Gladiolus dalenii (corms) and Protea simplex (leaves) showed good activity against Candida albicans. Twenty one extracts inhibited the COX-1 enzyme, while fifteen extracts inhibited the COX-2 enzyme at the lowest screening concentration of 62.5 ƒÊg/ml. The highest COX-1 inhibition at a concentration of 62.5 ƒÊg/ml was exhibited by Diospyros lycioides leaf PE extract (89.1%) while Agapanthus campanulatus root DCM extract showed the highest COX-2 inhibitory activity (83.7%) at the same concentration. In the Ames test, no genotoxicity was observed in any of the extracts, however more tests need to be done to confirm these results. Thin layer chromatograms of the organic solvent plant extracts were developed. The fingerprints of the plant extracts showed colours of bands at different Rf values when viewed under UV254 and UV366 suggesting that the investigated plant species contained different compounds in the extracts. In the quest to understand the source of the plants pharmacological activities, total phenolic compounds including condensed tannins, gallotannins and flavonoids were quantitatively investigated in terms of their amounts in the aqueous methanol extracts of the plants materials using spectrophotometric methods. Alkaloids and saponins were qualitatively determined. The amounts of total phenolics were determined by the Folin Ciocalteu assay, condensed tannins were determined by the butanol-HCl assay, while rhodanine and vanillin assays were used to determine the amounts of gallotannins and flavonoids respectively. Dragendorff reagent was used to detect alkaloids in the plant extracts on thin layer chromatographic plates, while the froth test was employed to detect saponins. Secondary metabolites varied with plant parts and species with Cyperus textilis (leaf) having the highest amounts of total phenolics, condensed tannins and flavonoids. The highest amount of gallotannins was detected in Protea simplex leaf extracts. All the investigated plant materials with the exception of Haworthia limifolia leaf, Protea simplex leaf, Antidesma venosum leaf and Dissotis princeps leaf tested positively to saponins. Alkaloids were detected in Haworthia limifolia leaf (PE and EtOH), Cucumis hirsutus leaf (EtOH), Becium obovatum root (DCM), Protea simplex root and bark (EtOH), Agapanthus campanulatus root (DCM) and leaf (EtOH), Cyperus textilis root (DCM), Vernonia natalensis leaf (PE), Antidesma venosum leaf (PE), Diospyros lycioides leaf (PE) and Dissotis princeps leaf (DCM) extracts. The results obtained from the investigation of the pharmacology and phytochemistry of the plant species used to treat microbial infections related to gastro-intestinal tracts, provide sufficient preliminary information to validate the use of some of the plants in traditional medicine. The information provided might be considered sufficient for further studies aimed at isolating and identifying the active compounds in the plant species, and evaluating possible synergism amongst the isolated compounds. / Thesis (M.Sc)-University of KwaZulu-Natal, Pietermaritzburg, 2009.