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Orientador: Daniela Cardoso Umbelini Cavallini / Orientador no exterior: Bruce A. Vallance / Coorientador: Caetano Martha Antunes / Banca: Bruce Vallance / Banca: Carla Fontana / Banca: Xiaonan Lu / Banca: Ligia Sassaki / Resumo: O trato gastrointestinal abriga a maior população de microrganismos no corpo humano, onde eles desempenham um papel importante na promoção da saúde do hospedeiro. A alteração na composição da microbiota pode levar à disbiose intestinal, que consequentemente desencadeia ou agrava doenças intestinais e extra-intestinais. Microrganismos benéficos também conhecidos como probióticos são constantemente investigados como uma terapia complementar nas doenças relacionadas à disbiose. No entanto, sua eficácia no tratamento de condições severas, como por exemplos as doenças inflamatórias intestinais (DII), é bastante variável e apresenta resultados controversos. Para abordar a importância de uma abordagem probiótica personalizada para tratar a inflamação intestinal, primeiro examinamos o efeito de bactérias personalizadas usando um modelo de colite induzida por produtos químicos. Os animais que receberam comensais isolados de suas próprias fezes foram mais protegidos contra a inflamação, pois mostraram sinais reduzidos de colite, menor dano histológico e menores níveis de marcadores inflamatórios, quando comparados aos ratos que receberam uma cepa probiótica comercial. Em seguida, o papel da mucina intestinal Muc2 e da enzima Core-1 que glicosilam foram explorados usando o modelo de colite infecciosa Citrobacter rodentium. A camada de muco intestinal é a primeira linha de defesa no intestino e é composta em grande parte pela mucina Muc2. Uma vez que quase todas as bactérias entéricas de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The intestinal tract harbours the largest population of microbes in the human body where they play an important role in promoting the health of their host. If the composition of these microbes is altered, this may lead to dysbiosis that triggers or exacerbates intestinal and extra-intestinal diseases. Probiotics have been investigated as a complementary therapy in dysbiosis-related diseases. However, their effectiveness in treating severe conditions such as Inflammatory Bowel Disease (IBD) is quite variable and have shown controversial results. To address the importance of a personalized probiotic approach to treat intestinal inflammation, we first examined the effect of personalized bacteria using a model of chemical induced colitis. The animals that received commensals isolated from their own feces were more protected against inflammation as they showed reduced signs of colitis, less histological damage and lower levels of inflammatory markers as compared to mice given a commercial probiotic strain. Next, the role of the intestinal mucin Muc2 and the Core-1 enzyme that glycosylates it were explored using the Citrobacter rodentium model of infectious colitis. The intestinal mucus layer is the first line of defense in the intestine and is largely composed of the secreted mucin Muc2. Since almost all enteric bacteria must cross the overlying mucus layer to infect the host, the mucus-enteric bacterial interactions provide fundamental knowledge about infectious diseases as well as inflammatory conditions linked to dysbiosis... (Complete abstract click electronic access below) / Doutor

University of Macau / Institute of Chinese Medical Sciences

Diarrhoeal disease is a major cause of mortality in children in developing countries. It also remains a serious problem among all age groups throughout the world. Whereas studies to determine the epidemiological and aetiological factors of diarrhoeal disease have been reported for other parts of South Africa and the world, as yet no information is available for the Eastern Cape. Therefore this study was undertaken to determine the factors for this area. Enteropathogens were compared for the different ages in the various population groups and, where possible, seasonal and geographical differences were emphasised. A total of 7 278 faecal samples were examined by six laboratories in the Eastern Cape during the period November 1988 to October 1990. Data was recorded noting the age, sex and population group of the patients. The towns selected were Port Elizabeth, Uitenhage, Cradock, Grahamstown and their surrounding areas. The isolation rates for the pathogens studied in the various population groups were compared to those reported in similar studies in other countries. The seasonal incidences of the various selected pathogens were compared with those reported from elsewhere in South Africa. It was thought that the higher temperature of summer may influence the finding in the White population group, while rainfall would play a greater role for the Coloured and Black populations. The geographical distribution of the pathogens emphasised the difference in living conditions between the different population groups. For example a generally higher infestation rate of Helminths occurred in rural areas and in the groups living under poorer conditions. The low isolation rates for certain bacteria and the large percentage of samples from which no pathogens were isolated indicate the need for further research. However, the finding should be valuable for determining Public Health priorities and in the management of outbreaks of diarrhoeal disease.

This study was undertaken to determine the effect of inflammatory bowel disease (IBD), in general, and one of its manifestations, growth retardation, in particular, on the self-image of adolescents. The conceptualization of adolescent self-image as described by D. Offer (1981) was the basis for the study's framework. The psychological, social, sexual, familial and coping selves, further classified into 11 separate content areas, comprised the adolescent self-image. A descriptive-comparative design was used to describe the self-image of adolescents with IBD and to compare the similarities and differences in self-image among the IBD adolescents with and without growth retardation and their healthy peers. A convenience sampling method was used to obtain 24 IBD subjects between the ages of 12 and 20, eleven of whom had growth retardation. A normative sample of adolescents (N = 1385) was used by permission of D. Offer for purposes of comparison with the IBD subjects. Data were gathered using the Offer Self-image Questionnaire for adolescents. The adolescents with IBD did not differ remarkably from the norm in their perceptions of self although a tendency among the females to have concerns about their body image and sexual maturation was demonstrated. The IBD subgroup without growth retardation reported self-image perceptions that were superior to the norm and the growth retarded subgroup in almost every category. The IBD subgroup with growth retardation reported a disturbed self-image in a number of areas. The males revealed disturbances primarily in body image and secondarily in emotional harmony, and adaptability to stress in the immediate environment, family relations, and sexual maturation. The females revealed self-image disturbances in sexual maturation and body image. The findings of the study suggest that growth retardation in the IBD adolescent may have a negative effect on self-image. The findings may demonstrate a more notable and broader effect of growth retardation on self-image in the males with IBD than in the females. / Applied Science, Faculty of / Nursing, School of / Graduate

This study deals with the nature and characteristics of the Gram negative bacterial flora of the intestine of the domestic pigeon. Columba livia was selected for this study because of the abundance of this species around the Classroom building on the University of the Pacific campus.

Objective: The aims of this project were to (a) perform a systematic review and meta-analysis of the associations between multiple neurological disorders (or neurological diseases) and potential influencing factors, including the association between fine particulate matter (PM 2.5) and intestinal dysfunction, and (b) investigate the mechanisms and toxicological effects of PM 2.5 exposure in the brain and intestines using a mouse model of Alzheimer's disease (AD). Design: A systematic review and meta-analysis was conducted to assess the risks of PM 2.5 exposure, as manifested by the incidence of exposure-associate neurological disorders or intestinal dysfunction. An APP/PS1 transgenic mouse model for AD was used to study the brain damage resulting from PM 2.5 exposure, and the miRNA/mRNA regulatory mechanisms contributing to this damage. The inflammatory injuries and bacterial community changes in the intestines of AD mice exposed to PM 2.5 were also investigated. Data sources: Articles for systematic review and meta-analysis were obtained by searching PubMed and China National Knowledge Infrastructure (CNKI), which were published for more than ten years. Animal experiments were conducted at Shanxi University of Taiyuan in China, and toxicological tests were performed according to the stipulated methods and protocols. Review and experimental methods: Data on the risks of incidence of neurological disorders associated with the environmental factor (PM 2.5) and biological factors (intestinal disorders and bacteria) were obtained, and random- or fixed-effects models (depending on the I 2 value) were used to pool the odds ratios (OR) with the 95% confidence intervals (CI) from individual studies. In the animal experiments, mice were divided into four groups of five animals per group, as follows: normal control mice in filtered air, AD mice in filtered air, normal control mice in PM 2.5 air, and AD mice in PM 2.5 air. PM 2.5 mice were exposed to ambient PM 2.5 in a whole-body inhalation exposure device for 8 weeks in Taiyuan, China. Well-established methods were used to explore the toxicological mechanisms by which PM 2.5 exacerbated brain damage in AD mice, namely open-field testing, enzyme-linked immunosorbent assay (ELISA), real-time quantitative RT-PCR, hematoxylin-eosin (HE) staining, and transmission electron microscopy (TEM). Brain damage and related biomarkers in the brains were measured, and miRNA and mRNA profiles were detected using high-throughput sequencing methods. The signaling pathways of miRNAs or mRNAs were predicted and summarized, and specific miRNAs and mRNAs were screened to explore the possible regulatory mechanisms of PM 2.5 -induced brain damage in AD mice. Intestinal and fecal samples from these mice were also subjected to 16S rRNA gene sequencing. HE staining, ELISA, and metagenome bacterial diversity analyses were performed to investigate the effects of PM 2.5 inhalation on intestinal tissue damage, inflammatory responses, and changes of bacterial diversity and communities in AD mice. Results: Long-term PM 2.5 exposure has been associated with increased risks of stroke, dementia, AD, autism spectrum disorder (ASD), and Parkinson's disease (PD) in humans, with the risks of ischemic and hemorrhagic stroke being higher than that of stroke in general. Furthermore, a relatively higher risk of stroke has been observed in heavily polluted countries compared to less polluted countries. It is known that some intestinal disorders and related problems such as constipation, inflammatory bowel disease, irritable bowel syndrome, small intestinal bacterial overgrowth, and diarrhea significantly increase the risks of developing AD or PD. For example, the risk estimates of Helicobacter pylori infection were significantly associated with AD and PD. From another angle, preliminary animal experimental results showed that PM 2.5 promoted brain morphological damage and decreased spatial exploration ability in AD mice, and was concomitant with increases in the concentrations of amyloid-β-42, acetylcholinesterase, tumor necrosis factor-α, and interleukin-6 and decreases in the concentrations of choline acetyltransferase. High-throughput sequencing and bioinformatics analyses revealed that miRNAs and mRNA had differential expression profiles subsequent to PM 2.5 exposure, which suggested that these species are involved in the molecular regulatory mechanisms and possible signal pathways of PM 2.5 -aggravated brain injury in AD mice. These PM 2.5 -aggravated brain injuries were correlated with pathological intestinal injury, inflammatory responses, and changes in bacterial diversity in the intestines and feces of PM 2.5 -exposed AD mice, and decreases in predominant bacteria were identified. These data will assist in delineating the ability of PM 2.5 exposure to induce pathological changes in the brain and gut tissue via the brain-gut axis and thereby aggravate AD. Conclusions: A systematic review and meta-analysis showed that there is a significant association between PM 2.5 exposure and the occurrence of stroke, dementia, AD, ASD, and PD, and a strong association between intestinal disorders and the presence of certain bacteria and the development of AD and PD. PM 2.5 (environmental factors) and intestinal disorders accompanied by changes in bacterial diversity (internal biological factors) appeared to be the two most important factors that increase the risk of developing neurological disorders. Experimental animal data showed that PM 2.5 potently damaged the brain and intestines of AD mice, and that the toxicological mechanisms of this PM 2.5 -mediated brain injury led to morphological changes, inflammation, and perturbation of miRNA/mRNA regulation in the brain. These data suggest that PM 2.5 inhalation also have modulatory effects on the abundance and diversity of intestinal bacteria in AD mice. The findings of this study have clarified positive relationships between environmental and biological factors and neurological disorders and have elucidated the potential mechanisms by which PM 2.5 may mediate the initiation or exacerbation of AD

The number of patients who are receiving home total parenteral nutrition (TPN) is increasing. This phenomenon is a result of rising hospital costs and legislation which encourages shorter hospital stays. Previous research has not demonstrated thoroughly change in nutritional status associated with TPN given over a long period of time to patients with singular disease entities such as Crohn's disease. Therefore, this study was undertaken. Two groups of patients were obtained: a sample of five hospitalized patients from a veterans' hospital, and a sample of fifteen home patients followed by a hospital-based nutritional support team. Both groups had Crohn's disease and were receiving TPN. The following parameters were measured: serum albumin, percentage of ideal body weight, and total iron binding capacity. Mean levels and standard deviations of each parameter per time period measured were obtained. These means were plotted across time periods. For each parameter, slopes for each time period were compared using a t-test. For the hospital group, time periods consisted of 20 day periods. For the home patients, time periods were 12 months in length. Mean levels of each parameter remained within normal limits within nearly all time periods for both groups. However, significant changes in each parameter in the home group occurred at the following time periods: 60- 72 months and 72-84 months for serum albumin; and 0-48 months and 48-120 months for total iron binding capacity. (No periods of significance occurred for changes in percentage of ideal body weight.) These changes might indicate periods of significant response to TPN. Other factors which also might have influenced these results include level of compliance by patient, other major illness, iron status, hydration status, effects of sample size, and protein-losing enteropathy. / M.S.

Orientador: Luiz Claudio Di Stasi / Banca: João Ernesto de Carvalho / Banca: Ligia Yukie Sassaki / Banca: Erick José Ramo da Silva / Banca: Carlos Augusto Real Martinez / Resumo: A Doença Inflamatória Intestinal (DII) engloba, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Colite Ulcerativa (CU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados de remissão dos sintomas. Apesar da DII ser objeto de pesquisa há várias décadas, a sua etiologia ainda é desconhecida e um único agente ou mecanismo isolado não parecem ser suficientes para produzir ou desencadear a doença. A dificuldade em se tratar de forma efetiva todos os pacientes com DII em função da baixa resposta aos fármacos associada a diversos efeitos colaterais corrobora a busca de novas fontes de compostos úteis no tratamento e prevenção da DII. Entre as várias estratégias disponíveis, a pesquisa de plantas medicinais se mostra promissora. Bidens pilosa L., família Asteraceae, é uma erva daninha com ampla distribuição e ocorrência em diversos países, sendo conhecida no Brasil como picão-preto. Apesar de ser considerada uma erva daninha sem importância econômica tem sido utilizada em várias populações com finalidade medicinal e sua aplicação em diversas enfermidades pode ser devido a sua composição química rica em phytol e ácido graxos poli-insaturados (ácido palmítico, ácido oleico ácido linoleico), compostos com efeitos anti-inflamatórios e/ou antioxidantes. No presente trabalho o extrato supercrítico de Bidens pilosa L. foi capaz de reduzir os níveis de mediadores pró-inflamatórios, como MPO, IL-1β e TNF-α além de modular fatores anti-inflamatórios como IL-10 tanto no protocolo preventivo quanto no curativo. Modulou também a expressão gênica de genes relacionados à inflamação e proteção da mucosa, como HSP70 e MUC. Além das alterações bioquímicas pôde-se notar uma melhora histológica em amostras de cólon analisadas por microscopia eletrônica. Associada a alterações estruturais ocorreu um ... / Abstract: Inflammatory Bowel Disease (IBD) comprises basically two distinct diseases: Crohn's disease (CD) and Ulcerative Colitis (UC), both characterized by chronic inflammation of the intestine, with exacerbation periods followed by long intervals of remission of symptoms. Despite being subject of research for decades, its etiology is still unknown and a single agent or isolated mechanism is not enough to produce or trigger the disease. The difficulty in effectively treat all patients based on the poor response to drug and in the several side effects that the treatments presents, supports the search for new sources of compounds useful in the treatment and prevention of IBD. Among the various strategies available, the research of medicinal plants shows promise. Bidens pilosa L., Asteraceae, is a weed with wide distribution and occurrence in some countries and is known in Brazil as picão-preto. Although it is considered a weed without economic importance, has been used in various populations with medical purpose and its application in various diseases may be due to its chemical composition rich in phytol and polyunsaturated fatty acid (palmitic acid, oleic acid and linoleic acid) compounds known to have anti-inflammatory and/or antioxidants effects. In the present study the supercritical extract of Bidens pilosa L. was able to reduce the levels of pro-inflammatory mediators, such as MPO, IL-1β and TNF-α associated with modulation of anti-inflammatory factors such as IL-10, both in the preventive and curative protocols. Also modulates gene expression of genes related to inflammation and mucosal protection, such as HSP70 and MUC. In addition to the biochemical changes might notice a histological improvement in colonic samples analyzed by electron microscopy. Together with structural changes was an increase in the production and secretion of mucin, mucosal protective agents. Thereby, B.pilosa extract is an important source of compounds which may ... / Doutor

Orientador: Cristiano Gallina Moreira / Banca: Clovis Wesley Oliveira de Souza / Banca: Fernando Rogério Pavan / Resumo: Sinalização química em bactérias patogênicas é um mecanismo empregado para interagir com o hospedeiro e sua respectiva microbiota. Através desta interação ocorre a regulação dos mecanismos de virulência. Estudando o mecanismo de sinalização química do sistema de 2-componentes QseBC em Salmonella enterica serovar Typhimurium foi aberta uma nova perspectiva para desvendar os mecanismos de patogenicidade. Dentre estes, uma nova proteína VisP (Virulence and stress-related Periplasmic protein) foi reportada. Seu papel inicial na interação com a enzima LpxO em S. Typhimurium foi anteriormente demonstrada. O antígeno-O da camada de LPS fornece proteção contra as defesas do hospedeiro e, particularmente, o comprimento de sua cadeia exerce um papel essencial. A montagem do antígeno-O possui o sistema Wzz, o qual determina o comprimento final de sua cadeia polissacarídica, e também apresenta uma distribuição tri-modal. Forma cadeias curtas (S-OAg), longas (L-OAg) e muito longas (VL-OAg) de antígeno-O. As proteínas WzzST e WzzfepE regulam, respectivamente, a síntese das cadeias L-OAg e VL-OAg. Neste estudo, os genes wzzST, wzzfepE, visP e lpxO foram mutados, via mutagênese λ Red, obtendo simples e duplos mutantes. Dados preliminares evidenciaram que há um aumento nas cadeias VL-OAg e L-OAg no mutante ΔvisP, e reciprocamente há diminuição de L-OAg em ΔlpxO. Foram feitos ensaios para avaliar a motilidade, invasão em células epiteliais e sobrevivência intracelular em macrófagos com as amo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Chemical signaling is a mechanism employed by several bacterial species to interact within surrounding microbiota and their host. Upon this interaction the pathogenic bacteria regulate their virulence traits. The two-component system QseBC was described on chemical signaling in Salmonella enterica serovar Typhimurium, and a novel branch of pathogenic cascade regulation was revealed. Among these mechanisms a novel protein was described, VisP (Virulence and stress related Periplasmic protein). VisP interacts with LpxO enzyme on the periplasm. The O-antigen of the LPS layer provides protection against host defenses, and particularly its chain's length plays an essential role. The O-antigen assembly has the Wzz system, which determines the O-antigen final chain length, and also presents a tri-modal distribution. It forms short (S-OAg), long (L-OAg) and very-long (VL-OAg) O-antigen chains. The WzzST and WzzfepE proteins respectively regulate the L-OAg and VL-OAg synthesis. In this study, wzzST, wzzfepE, visP and lpxO genes were mutated via λ Red mutagenesis, obtaining single and double-mutants. Our preliminary data have shown that VisP increases VL-OAg and L-OAg, conversely LpxO diminishes L-OAg chain length. The motility, epithelial cell invasion and macrophage intracellular survival and replication were assessed with the mutants obtained. The ΔvisP presented 1,2 and 1,0 order of magnitude reduction in cell invasion and intracellular macrophage replication, respectively, compari... (Complete abstract click electronic access below) / Mestre