Thesis (M.S.P.H.)--University of Michigan, 1938.

Thesis (M.S.P.H.)--University of Michigan, 1938.

Proefschrift - Utrecht. / Summary in English.

Thesis (Ph. D.)--University of Oregon, 2003. / Includes bibliographical references (leaves 137-145).

It had long been known that individuals with inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), have locally reduced vitamin C levels in the intestinal mucosa, which equates to an overall loss of the antioxidant capacity and increase risk of oxidative tissue damage. The aim of the present work was to expand on this concept, through investigating the role of genetic variations in intestinal vitamin C transporters in vulnerability to IBD and further characterizing their functions. The studies focused on a known intestinal transporter for ascorbic acid, SLC23A1, and a novel intestinal transporter of dehydroascorbic acid, SLC2A14 (GLUT14). To investigate any association between the SLC23A1 and SLC2A14 with IBD, genomic DNA of 311 Caucasian individuals with IBD, participated in the Manitoba IBD Cohort Study, and 142 healthy controls were genotyped for tagging single nucleotide polymorphism (SNP) of each gene, using TaqMan Assays. New splice variants of SLC23A1 and SLC2A14 were determined by In silico analyses, followed by sub-cloning of the splice variants to verify their subcellular locations. Substrates and functions were determined, using the Xenopus laevis oocyte system for each transporter. The presence of the SLC23A1 variant rs10063949 G allele elevated the risk for CD by 150% (Odds ratios (OR) = 2.54, 95% CI 1.83-3.53). An allele dosage effect was confirmed; compared to rs10063949-AA homozygotes the 10063949-AG heterozygotes have a 150% elevated risk and the 10063949-GG homozygotes have a 370% elevated CD risk (OR=2.54, 95% CI 1.38-4.66; OR=4.72, 95% CI 2.53-8.81, p<0.001; respectively). No relation was observed between genetic variants in SLC23A1 and UC. Through database search, a novel 5’exon was discovered for SLC23A1 locus which is located 1078 nucleotides upstream of the canonical first exon. The two first exons are not mutually exclusive since they splice together to create a novel SLC23A1 protein isoform, we named it isoform 1A, with a N-terminus that is elongated by 36 amino acid. The novel SLC23A1 isoform located at the plasma membrane, but mediates only 7% of the ascorbic acid transport exhibited by the shorter isoform. The presence of the SLC2A14 SNP rs2889504 A allele elevated the risk for UC by 260% and CD by 468% (OR: 3.60, 95% CI: 1.95-6.64; OR: 4.68, 95% CI: 2.78-8.50, respectively). The rs10846086-G allele elevated the risk of UC and CD approximately 3-fold (OR: 2.91, 95% CI: 1.49-5.68; OR: 3.00, 95% CI: 1.55-5.78, respectively). The variant rs12815313-T increased the risk for CD by 112% (OR: 2.12, 95% CI: 1.33-3.36). All the genetic variations in SLC2A14 gene, associated with IBD, were independent from each other, strengthening the evidence that functional SNPs in the SLC2A14 locus contribute to IBD. It was identified that the two major GLUT14 isoforms locate to the plasmalemma membrane and mediate cellular uptake of dehydroascorbic acid. Significant expression in extra-testicular tissues was confirmed for SLC2A14, notably in intestinal segments, explaining the association with IBD. Re-analysis of genomic showed a dramatically expanded locus of SLC2A14, containing twenty exons which covered 103,477 nucleotides from the first Transcriptional Start Site (TSS) to the termination of the longest transcript. All together, the presented evidence indicate that functional SNPs in the SLC2A14 gene and SLC23A1 could contribute to vitamin C imbalance in mucosal cells which contributes to an elevated risks of IBD. Furthermore, novel information about genetic and functional characteristics of SLC23A1 and GLUT14 transporters was identified. / February 2016

No description available.

Orientador: Luiz Claudio Di Stasi / Resumo: A Doença Inflamatória Intestinal (DII) é uma doença com etiologia desconhecida e sem terapêutica curativa disponível, englobando, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Retocolite Ulcerativa (RCU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados com remissão dos sintomas, cujo tratamento com os fármacos disponíveis apresentam sérios efeitos colaterais. Portanto, o desenvolvimento de novas estratégias de tratamento que combinem eficácia e segurança é uma importante meta na terapia da DII. Produtos de origem natural, especialmente oriundos de fontes vegetais com propriedades de modificar a microbiota intestinal têm sido amplamente estudados como agentes preventivos e/ou curativo destas doenças, visto que a manipulação da microbiota intestinal tem se mostrado como uma estratégia importante na manutenção da homeostase colônica. Neste contexto, muitos frutos de origem tropical, com ampla utilização pela população e ricos em fibras e/ou componentes que ativos como antioxidantes e/ou anti-inflamatórios podem representar uma nova estratégia complementar para a prevenção ou cura da DII. Dentre eles se destacam os frutos das espécies Theobroma grandiflorum (cupuaçu) e Musa spp AAA (banana nanica), ricos em fibras alimentares e compostos fenólicos, os quais são potencialmente benéficos no tratamento e prevenção da DII. O objetivo do presente trabalho foi avaliar os efeitos de uma d... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Orientador: Taís maria Bauab / Banca: Luis Vitor Silva do Sacramento / Banca: Carlos Henrique Gomes Martins / Resumo: A família Eriocaulaceae é amplamente distribuída no Brasil, popularmente são conhecidas como "sempre viva" porque, mesmo após o corte e secagem, conservam a cor e forma por vários anos. O objetivo deste trabalho foi determinar o potencial biológico de P. geniculatus, estudando a atividade antimicrobiana, antioxidante e a motilidade intestinal dos extratos diclorometânico, metanólico e hexânico. Para determinação da atividade antimicrobiana foram utilizadas as técnicas de difusão em ágar e microdiluição. Para determinação do potencial antioxidante foram realizados os ensaios espectrofotométricos: radical ABTS●+, DPPH, determinação dos teores de fenóis e flavonóides totais, utilizando como padrões a quercetina e ácido gálico. Na técnica de difusão em ágar, 100\L de suspensão bacteriana a concentração de 108 UFC/mL foram semeadas em ágar Muller Hinton e ágar Sabouraud. Discos de papel foram embebidos com 25\L das amostras vegetais e dispostos na superfície das placas de Petri. Após incubação a 37ºC por 24 horas em aerobiose foram feitas as leituras dos halos de inibição de crescimento ao redor dos discos (mm). No teste de microdiluição os orifícios das microplacas foram preenchidos com 80\L de caldo de Muller Hinton, 100\L de soluções da amostra vegetal diluída seriadamente de 1000 a 7,81\g/mL e 20\L da cultura a concentração de 107 células/mL para as bactérias e 103 células/mL para as leveduras. As microplacas foram incubadas a 37ºC durante 24 horas sob condições de aerobiose e posteriormente determinou se a CBM e CFM. Na avaliação da motilidade intestinal, foram utilizados os extratos de escapos e capítulos no solvente diclorometano e metanólicos (250mg/kg), um controle positivo (cloridrato de loperamida, 5mg/kg), controle negativo (solução fisiológica), controle do solvente (Tween 80 a 20% de metanol). Após 45 minutos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The family Eriocaulaceae is distributed over several parts of Brazil, are popularly known as "evergreen" because even after cutting and drying, retain their color and shape for many years. This work was to determine the biological potential of P. geniculatus, studying the activity antimicrobial, antioxidant and assess the motility of the extracts dichloromethanic, methanolic and hexanic. For activity determination as techniques were used antibacterial ágar diffusion and microdilution against Gram positive and Gram negative bacterium and yeasts. To determine the potential antioxidant spectrophotometric assays were performed: radical ABTS●+ , DPPH, determining the levels of phenolics and flavonoids, using standards as quercetin and gallic acid. In the diffusion technique , 100 mL of bacterial suspension concentration of 108 CFU/mL were seeded in Muller Hinton ágar and Sabouraud broth with Drigalski loop. Discs paper with 10 mm in diameter soaked with 25\L of vegetation samples were arranged on the surface of the plates. After incubation at 37 ° C for 24 hours under aerobic conditions were the readings of the inhibition of growth around the disks, measured in millimeters. In test microdilution holes of the microplate were filled with 80\L Muller Hinton broth , 100 mL of sample solutions of serially diluted plant 1000 to 7,81 \g/mL and 20\L of bacterial culture concentration of 107 cells/mL and 103 cells/mL for yeasts. The microplates were incubated at 37 ° C for 24 hours under aerobic conditions and subsequently became the technique of CBM and CFM. In the evaluation of intestinal motility, were used extracts of scapes and chapters in dichloromethane solvent and methanol (250mg/kg), a positive control (loperamide hydrochloride, 5mg/kg), negative control (saline solution), control of the solvent (Tween 80 to 20% methanol). After about 45 minutes the animals received a suspension activated... (Complete abstract click electronic access below) / Mestre

Orientador: José Ricardo de Arruda Miranda / Resumo: Atividades motoras gástricas e intestinais representam um complexo grupo de funções essenciais à vida, sendo o estudo de suas características objeto de grande interesse da comunidade científica. Estudos sobre essas atividades foram intensificados em decorrência da elevada prevalência de indivíduos com sintomas atribuíveis às anormalidades dessas funções. Além disso, uma vez que os mecanismos das disfunções motoras do trato gástrico e intestinal ainda não se acham plenamente esclarecidos, faz-se necessária a busca de novas abordagens. Várias metodologias têm sido empregadas na avaliação dos parâmetros contráteis da motilidade gástrica e intestinal – uso de strain gage, métodos barométricos, elétricos e cintilográficos. A biosusceptometria de corrente alternada é um método alternativo eficaz e que apresenta grandes vantagens em relação aos demais e nesse trabalho foi comparada a técnicas consideradas padrão na avaliação da oscilação tônica do estômago e dos diferentes trechos do intestino delgado. Os resultados apresentaram valores fortemente correlacionados e concordantes entre si, permitindo quantificar a atividade tônica e o espectro de frequências predominantes nos diferentes segmentos do intestino delgado. Este trabalho aplicou uma metodologia eficiente na avaliação da oscilação tônica do estômago e do espectro de frequências predominantes no duodeno, jejuno e íleo. / Doutor

Introduction Patients with intestinal failure (IF) develop problems of malabsorption and malnutrition associated with short bowel syndrome (SBS). Home parenteral nutrition (HPN) became available to treat these patients since the 1970s. There is a paucity of qualitative research on patients’ experiences in the UK. The study aim was to generate theory that explains the experiences of adults living with HPN and complex medication regimens. Method The grounded theory methodology was used to explore the experiences and to generate theory about this health intervention. Twelve participants were interviewed. The interviews were recorded and transcribed verbatim. The joint process of data collection and analysis followed the principles of constant comparative approach. Results The core categories of stoma care and HPN treatment were supported by the subcategories of maintaining stoma output, access to toilets, maintaining HPN infusion routine, access to technical help to set up HPN infusion, and general health changes. Strategy used to manage living with loss was demonstrated by the subcategory of maintaining daily activities and social interactions. Discussion The theory of living with loss suggests that patients with a stoma receiving HPN experience the sense of loss at home and in social situations. Opportunities for professional practice development are detailed along with implications for future research. Conclusions The findings resonate with the Kubler-Ross Model of the five stages of grief (Kubler-Ross, 1970). The theory of living with loss was generated by the use of the grounded theory methodology. This study identified opportunities for changes and improvement in clinical practice.