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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
471

Interleukin-1 Beta Mediated Regulation of Hyaluronan and Hyaluronan Synthase 2

Ducale, Ashley Elizabeth 01 January 2005 (has links)
Elevated levels of hyaluronan are associated with numerous inflammatory diseases including ulcerative colitis, Crohn's disease and wound healing. Various proinflammatory cytokines have shown to influence hyaluronan expression in cells originating from connective tissue. The overall purposes of this study included: 1. To determine the effects of IL-1β stimulation on HA and HAS2 steady state transcript levels and the signaling pathways involved in its effects. The signaling pathways utilized by proinflammatory mediators to modulate hyaluronan expression have only begun to be elucidated. In this aim, the effects of IL-1β on hyaluronan and HAS expressions in jejunum-derived mesenchymal cells were determined. Inhibition studies were utilized to determine the signaling pathways involved. The overall hypothesis of this aim was that stimulation of jejunum-derived mesenchymal cells with IL-1β activates the mitogen activated protein kinase pathways resulting in increased HAS2 steady state transcript and hyaluronan levels.Results: The results suggest that IL-1β induction of HAS2 expression involves, in part, the mitogen activated protein kinase signaling pathways that act in concert thus leading to an increase in expression of hyaluronan by jejunum-derived mesenchymal cells.2. To determine the effects of dexamethasone on IL-1β mediated increase in hyaluronan and HAS2 expressions and the mechanisms utilized by this glucocorticoid. Glucocorticoids are a mainstay treatment for the inflammatory component of inflammatory bowel disease. Given the recent evidence demonstrating increased hyaluronan in inflamed tissue from patients affected with inflammatory bowel disease, the objective of this aim was to determine the effect of dexamethasone on IL-1β-mediated induction of hyaluronan. The hypothesis of this aim was that pre-treatment with dexamethasone suppressed the ability of IL-1β to increase HAS2 transcript and hyaluronan levels via inhibition of the p38 MAP kinase pathway. Results: Pre-treatment with dexamethasone inhibited IL-1β-mediated hyaluronan and HAS2 induction by blocking the activation of the p38 MAP kinase pathways. 3. To identify the transcriptional and post-transcriptional mechanisms utilized by IL-1β to upregulate HAS2 steady state transcript levels. Very little is known about transcriptional and post-transcriptional regulation of the hyaluronan synthase 2 gene. In this aim, 5' and 3' mapping, luciferase analyses and actinomycin D studies were used to determine the transcriptional and post-transcriptional mechanisms utilized by IL-1β to regulate HAS2 steady state transcript levels. The hypothesis of this aim was that IL-1β used post-transcriptional mechanisms to regulate the HAS2 gene.Results: Dermal fibroblasts were used to find the 5'- and 3'-termini of the HAS2 message. Promoter constructs extending approximately 1 kb upstream from the transcription start site demonstrated no IL-1β response. Blocking protein synthesis prior to the addition of IL-1β dramatically increased HAS2 steady state transcript levels, while inhibition of transcription suppressed the effect of IL-1β on HAS2. Northern blot analysis revealed that cycloheximide and IL-1β exerted differential effects on the two HAS2 transcripts.
472

Monitoring of azathioprine therapy in pediatric population : relationship between pharmacokinetics pharmacodynamics in inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) / Optimisation thérapeutique de l’azathioprine dans la population pédiatrique : relation pharmacocinétique pharmacodynamie dans la maladie inflammatoire de l’intestin et dans l’hépatite autoimmune

Nguyen, Thi Van Anh 03 July 2013 (has links)
La présente étude a pour objectif de mettre en évidence l‘intérêt du suivi thérapeutique pharmacologique (STP) des métabolites thiopuriques en vue de l‘optimisation du traitement par l‘azathioprine chez les enfants atteints de maladie inflammatoire de l‘intestin et d‘hépatite autoimmune. Les travaux réalisés nous ont permis de montrer, en utilisant une analyse multi-niveaux, une corrélation significative entre la dose d‘azathioprine et les concentrations en 6-TGN et Me6-MPN ainsi qu‘avec le ratio Me6-MPN/6-TGN confortant l‘utilisation des métabolites pour ajuster la posologie d‘azathioprine chez les enfants présentant une maladie inflammatoire de l‘intestin. Différents facteurs pouvant modifier les concentrations de métabolites thiopuriques ont été identifiés. La co-administration d‘infliximab a conduit à une augmentation significative des concentrations de 6-TGN. Des concentrations plus faibles de 6-TGN ont été observées chez les jeunes enfants suggérant l‘influence de l‘âge sur le métabolisme ou sur l‘absorption de l‘azathioprine. Nous avons également montré qu‘une concentration de 6-TGN supérieure à 405 pmol/8.108RBCs chez des patients ayant une activité TPMT normale et pour lesquels la rémission clinique n‘a pas pu être obtenue en l‘absence de stéroïdes, était prédictive d‘une résistance à l‘azathioprine. Un seuil de 250 pmol/8.108RBCs en 6-TGN est significativement associé à une meilleure réponse thérapeutique. D‘autre part, une corrélation a été observée entre les métabolites thiopuriques et la leucopénie. Chez les enfants atteints d‘hépatite autoimmune, une corrélation positive entre la dose d‘azathioprine et les concentrations de métabolites a été retrouvée. L‘importante variabilité inter-individuelle dans les concentrations en métabolites thiopuriques et dans la réponse thérapeutique a été confirmée démontrant l‘intérêt d‘une individualisation de la thérapeutique. L‘instauration d‘un STP des métabolites thiopuriques associé au suivi hématologique, à la détermination de la TPMT et au suivi clinique paraît justifié afin d‘optimiser la thérapeutique par l‘azathioprine dans la population pédiatrique / The present study aimed to investigate the usefulness of thiopurine metabolite monitoring in pediatric inflammatory bowel disease (IBD) and Autoimmune Hepatitis (AIH) for optimizing azathioprine therapy. Using multilevel analysis, we demonstrated for the first time the significant positive correlations between the weight-based azathioprine dosage and the 6-thioguanine nucleotide (6-TGN) and 6-methyl-mercaptopurine (6-MeMPN) levels as well as 6-MeMPN/6-TGN ratio, supporting the use of metabolites to adjust dosing in IBD children. Other factors affecting metabolite levels were also identified. Co-administration of infliximab resulted in a significant increase in 6-TGN levels. Younger children exhibited lower metabolite levels, suggesting the influence of age on metabolism/absorption of azathioprine. We also reported that a 6-TGN level above 405 pmol/8.108RBCs in IBD children with normal TPMT activity who did not achieve steroid-free clinical remission was predictive of azathioprine refractoriness. A cut-off of 250 pmol/8.108RBCs for 6-TGN was found to be significantly associated with higher therapeutic response. Moreover, both 6-TGN and 6-MeMPN levels were correlated with leucopenia. In AIH children, a positive correlation between azathioprine dosage and metabolite levels was also observed. The wide variability in thiopurine metabolites and therapeutic response in both IBD and AIH children was confirmed, pointing to the important role of treatment individualization. Monitoring of thiopurine metabolites combined with hematological tests, TPMT activity and clinical evaluation may be of interest for optimizing thiopurine therapy and minimizing toxicity in IBD and AIH children
473

Komplikace sondové enterální výživy u idiopatických střevních zánětů / Complications of tube enteral feeding in inflammatory intestine diseases

Polachová, Monika January 2019 (has links)
The diploma thesis is devoted to complications of enteral nutrition in patients with idiopathic inflammatory bowel diseases. The incidence of these diseases has increased in recent years. Nutritional support is an important part of the treatment and the possibility of improving the nutritional status of patients, which plays an important role in responding to other forms of treatment itself or in pre-operative preparation. All forms of artificial nutrition might also cause certain complications. The subject of this work is to observe the complications of enteral nutrition, their solutions and the possibilities of their prevention.
474

AeMOPE-1: um novo peptídeo imunomodulador salivar de Aedes aegypti com potencial terapêutico na colite experimental. / AeMOPE-1: a novel salivary immunomodulatory peptide of Aedes aegypti with therapeutic potential in experimental colitis.

Lara, Priscila Guirão 18 July 2017 (has links)
Os mosquitos representam o grupo mais importante de vetores de doenças infecciosas para o homem. Para que possam ter sucesso no repasto sanguíneo e sejam capazes de adquirir os nutrientes necessários para a maturação dos ovos, a saliva desses vetores possui atividades anti-hemostáticas e imunomoduladoras. Sabendo-se da importância da saliva dos artrópodes hematófagos para sua alimentação e para a transmissão de patógenos causadores de doenças o objetivo deste estudo foi caracterizar as atividades imunomoduladoras de um peptídeo descrito no salivoma de A. aegypti, presente somente em glândulas salivares de mosquitos fêmeas e cujo papel biológico ainda é desconhecido. Observou-se que o peptídeo denominado AeMOPE-1 inibiu a produção de mediadores pró-inflamatórios por macrófagos ativados, assim como induziu a resposta imune para o perfil Th2. O tratamento com o AeMOPE-1 reduziu os sintomas clínicos da colite experimental. Essa é a primeira descrição de um peptídeo salivar de A. aegypti com atividade imunomoduladora em macrófagos e com potencial ação terapêutica. / Mosquitoes are the most important vectors of pathogens that causing infectious to humans. To female succeed in their hematophagous habit and thus acquire the nutrients necessary for the maturation of their eggs, their saliva has components with anti-hemostatic and immunomodulatory activities. Thus, the aim of this project was to study the role of a novel salivary peptide described in the A. aegypti sialome, present only in female salivay glands, whose biological functions are still unknown. It was observed that the peptide named AeMOPE-1 inhibited the production of pro-inflammatory mediators by activated macrophages, as well as induced the immune response to the Th2 profile. Treatment with AeMOPE-1 reduced the clinical symptoms of experimental colitis. This works presents the first salivary peptide from A. aegypti with potent activity on macrophage biology and potential clinical application.
475

You Tube as a Source of Information for Irritable bowel Syndrome: a Critical Appraisal

Balagoni, Harika, Mando, Rufaat, Reddy, Keerthy, Bansal, Apurva, Aregbe, Adegbemisola, Bajaj, Kailash, Zheng, Shimin, Dula, Mark, Kozinetz, Claudia, Cuervo-Pardo, Nathaly, Young, Mark, Reddy, Chakradhar, Gonzalez-Estrada, Alexei 11 April 2017 (has links)
Introduction: Irritable Bowel Syndrome (IBS) is estimated to affect 11% of the population globally with a significant female predominance. IBS appears to afflict all age groups and socioeconomic conditions, thus making it a disease that permeates a very large part of society. While often debilitating, only 30% of those with IBS will indeed visit their physician. In an era dominated by social media, it is no surprise that 40% of all consumers report that online information affects the way they deal with their health. YouTube is one of the top 5 most accessed online resources for medical information. The strong reliance on online information as well as the rising prevalence of IBS has prompted us to determine the educational quality of IBS YouTube videos. Methods: We performed a YouTube search using the keywords “Irritable Bowel Syndrome” from September 3-25, 2016. The top 297most viewed videos were included and analyzed for characteristics, source, as well as content. The source was classified as healthcare provider, alternative medicine provider, patient and/or parents, company, media, or professional society. Content was further classified as medical professional education, advertisement, personal experience, patient education, alternative treatment or increase awareness. A scoring system was designed based on current accepted guidelines from multiple professional and academic societies to evaluate quality (-10 to +25 points). Negative points were assigned for misleading information. Videos were also scored by a global quality score. Six blinded reviewers were asked to view the videos and score each video independently. Results: A total of two hundred and ninety-seven videos were analyzed, with a median of 6,671 views, 25 likes, and 2 dislikes. Females were most commonly depicted (36.4%). The most commonly depicted race was White/Caucasian (62.0%). Among video sources, alternative medicine was most represented (32.3%) with treatments that included water fasting, yoga, hypnotherapy, frequency healing, massage therapy, and essential oil therapy. The least represented source was professional societies such as hospitals (5.4%). Mean scores were statistically different from each other (pConclusion: YouTube videos on IBS are mostly produced by alternative treatment sources with often controversial treatments that did not align with Page 16 2017 Appalachian Student Research Forum current evidence based guidelines. Furthermore, videos from healthcare professionals provided better and more accurate quality of information compared to other sources.
476

Youtube as a Source of Information for Inflammatory Bowel Syndrome: A Critical Appraisal

Mando, Rufaat, Balagoni, Harika, Reddy, Keerthy, Bansal, Apurva, Aregbe, Adegbemisola, Cuervo-Pardo, Nathaly, Bajaj, Kailash, Zheng, Shimin, Dula, Mark, Kozinetz, Claudia, Young, Mark, Chakradhar, Reddy, Gonzalez-Estrada, Alexei 01 April 2017 (has links)
Abstract available on the publisher's website.
477

Aspectos nutricionais na população de pacientes com síndrome do intestino irritável atendidos no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo / Nutritional concerns in the population of patients with irritable bowel syndrome treated at the Hospital of the School of Medicine, University of São Paulo (HCFMUSP)

Amarante, Daiana 28 May 2013 (has links)
INTRODUÇÃO: A síndrome do intestino irritável (SII) é uma doença funcional do trato gastrintestinal que afeta até 20% da população adulta. Os principais sintomas envolvem o mau funcionamento do intestino, associados com dores abdominais, manifestação de diarreia ou constipação, sem alterações estruturais e bioquímicas do intestino. A maneira mais adequada de tratar o paciente é por meio de uma abordagem ampla e integral, porém individualizada, com identificação dos fatores desencadeantes e/ou agravantes da sintomatologia, inerentes a cada paciente. Em todos os níveis de atendimento, deve-se orientar o paciente com relação à dieta. OBJETIVO: o principal objetivo do estudo foi avaliar os alimentos desencadeadores de sintomas nos pacientes com diagnóstico de SII atendidos no ambulatório especializado do Serviço de Gatroenterologia Clínica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Além disso, foram avaliados dados clínicos, estado nutricional, ingestão alimentar e hábito intestinal desta população. METODOLOGIA: foram avaliados 140 pacientes que preencherem o critério de Roma III. As informações foram obtidas por meio de inquérito clínico e dietético aplicado pela nutricionista no momento da consulta e pela revisão do prontuário. Os dados coletados foram: idade, sexo, grau de escolaridade, peso, altura, hábito intestinal, sintomas, aspecto das fezes, alimentos menos toleráveis e consumo alimentar. RESULTADOS: Dos pacientes avaliados, 63% estavam eutróficos. Dor abdominal, flatulência/distensão, sensação de evacuação incompleta e sensação de estufamento abdominal foram mencionadas por mais de 60% dos pacientes. Houve associação significativa entre aspecto das fezes e habito intestinal. Intolerância alimentar foi mencionada por 82,8% dos pacientes. Os alimentos citados pelos pacientes como exacerbadores dos sintomas foram frituras em geral, leite, massas com molhos, feijão, chocolate, café, pizza, repolho, tortas e doces. Constataram-se correlações estatisticamente significativas entre consumo de frituras e flatulência, chocolate e pizza com sensação de estufamento abdominal, margarina com constipação, leite com presença de muco nas fezes, pão branco com pirose retroesternal, massas com molho com dor abdominal e feijão com sensação de estufamento abdominal. CONCLUSÕES: o presente estudo revelou alta prevalência de intolerância alimentar na população ambulatorial de pacientes com SII atendida no HCFMUSP. Os principais alimentos desencadeadores e exacerbadores de sintomas/sinais foram identificados, devidamente listados e servirão para nortear a abordagem dietética nesses pacientes em futuros estudos / INTRODUCTION: Irritable Bowel Syndrome (IBS) is a functional disorder of the GI tract that affects about 20% of the adult population. The main symptoms involve the malfunction of the bowel, associated with abdominal pain, diarrhea or constipation manifestation, without providing structural and biochemical alterations of the intestine. The most appropriate way to treat the patient is through a broad and comprehensive approach, but individualized, trying to identify the factors triggering or aggravating symptoms, inherent to each patient. At all levels of care, the patient should be guided regarding diet. OBJECTIVE: The primary objective of the study was to evaluate the group of foods that exacerbate or trigger symptoms/signs in IBS patients treated in the outpatient clinic of our hospital. Additionaly, we evaluated clinical characteristics and nutritional features such as nutritional status, food intake and bowel habits. METHODOLOGY: 140 patients who met were studied in the present work. Information was obtained through clinical and dietary surveys at the appointment by a nutritionist and by chart review. Data collected included age, sex, educational level, height, weight, bowel habits, symptoms, appearance of feces (Bristol Scale), food intake and food intolerance (aliments that exacerbate or trigger symptoms/signs). RESULTS: Among the patients, 63% were eutrophic. Abdominal pain, flatulence / bloating, sensation of incomplete evacuation and abdominal bloating was mentioned by over 60% of patients. There was a significant association between the appearance of the feces and bowel habits. Food intolerance was mentioned by 82.8% of patients. Foods most cited by patients as exacerbating or triggering IBS symptoms were fried foods in general, milk, beans, chocolate, coffee, cabage and pastries (i.e pasta, pizza). Statistically significant correlations were detected between consumption of fried foods and flatulence; chocolate and pizza and bloating; margarine and constipation; milk and mucus in feces; white bread and heartburn; pasta with sauce and beans and abdominal pain and bloating. CONCLUSIONS: This study revealed a high prevalence of food intolerance in our outpatient population of IBS patients. The main food triggers of IBS symptoms/signs were identified, duly listed and will certainly guide the dietary approach in IBS patients in future studies
478

Gastrosquise fetal isolada: relação entre dilatação intestinal e resultados perinatais adversos / Isolated fetal gastroschisis: relation between bowel dilation and adverse perinatal outcome

Luciana de Freitas Garcia 30 November 2011 (has links)
Objetivos: Este estudo foi desenvolvido para avaliar o diâmetro transverso da alça intestinal exteriorizada como fator preditor de resultado adverso, nas gestações com gastrosquise fetal isolada. Métodos: Estudo retrospectivo envolvendo 94 gestações únicas. Foi realizada a medida do diâmetro transverso da alça intestinal (DTA) herniada, por meio da ultrassonografia antenatal, até 3 semanas antes do parto. Foi considerado resultado perinatal adverso: óbito intra-útero, óbito neonatal e complicações intestinais. Resultados: a última medida ultrassonográfica do DTA foi realizada com 35,6 ± 1,6 semanas e o tempo médio do intervalo entre a última medida e o parto foi de 6,2 ± 5,0 dias. Ocorreram 10 (10,6%) casos de óbitos intraútero e neonatal; foram observadas complicações intestinais em 8 (8,5%) casos. DTA 15, 20, 25 e 30 mm foram identificadas em 87, 46, 13 e 4% das gestações com prognóstico favorável, respectivamente. O DTA 25 mm apresentou valores de sensibilidade de 38%, e, valores preditivo positivo e preditivo negativo de 38% e 87%, na predição de resultados adversos. Para o DTA 30 mm, os valores foram: 19, 50 e 85%. A área sob a curva ROC do valor observado/esperado do DTA para cada idade gestacional foi de 0,67, sendo o melhor ponto-de-corte em 1,39; e, seus valores preditivos foram semelhantes aos do DTA 25 mm. Dilatação intestinal esteve significantemente associada com baixa taxa de fechamento primário da parede abdominal, longo período para iniciar a dieta via oral e internação hospitalar prolongada. Conclusões: Dilatação intestinal demonstrada até 3 semanas antes do parto é preditora de complicações intestinais e está associado a baixa taxa de fechamento primário da parede abdominal, longo período para iniciar a dieta via oral e de internação hospitalar / Objectives: Evaluate bowel diameter as a predictor of adverse outcome in isolated fetal gastroschisis. Methods: Retrospective study involving 94 singleton pregnancies. Ultrasound measurements of herniated bowel transverse diameter (BTD) were performed up to 3 weeks before delivery. Adverse outcome was intrauterine/ neonatal death and/or bowel complications. Results: Last BTD was recorded at 35,6 ± 1,6 weeks and mean interval to delivery was 6,2 ± 5,0 days. Intrauterine/ neonatal death occurred in 10 (10,6%) cases; bowel complications were observed in 8 (8,5%). BTD 15, 20, 25 and 30mm were found in 87, 46, 13 and 4% of pregnancies with a favorable outcome, respectively. BTD 25 mm sensitivity was 38%, positive and negative predictive values, 38% and 87%. For BTD 30 mm, the values were: 19, 50 and 85%. Observed/expected BTD ROC curve showed an area of 0,67, with best cut-off at 1,39; prediction values were similar to those for BTD 25 mm. Bowel dilatation was also significantly associated with lower rate of primary surgical closure, longer period to full oral feeding and prolonged hospital stay. Conclusions: Bowel dilatation demonstrated up to 3 weeks before delivery is a predictor of intestinal complications and is associated with lower rate of primary surgical closure, longer period to achieve full oral feeding and hospital stay
479

“Para seu intestino funcionar melhor, coma mais fibras e tome 2 litros de água por dia” : o que há de verdadeiro nesta recomendação?

Gonçalves, Gissele Vargas da Rosa January 2016 (has links)
Fundamento e objetivo: Mudanças na ingestão de fibra e água podem influenciar a fisiologia intestinal. Este conceito simplista fundamenta a recomendação médica popular de aumentar o consumo de fibras e ingerir 2 litros de água por dia para o tratamento da constipação intestinal. O nosso objetivo foi avaliar o que há de verdadeiro nesta recomendação, primeiramente em indivíduos saudáveis. Métodos: Neste ensaio clínico randomizado, não cego, de grupos paralelos, 20 voluntários sadios tiveram suas variáveis basais determinadas (dieta, hábito intestinal, qualidade de vida e microbiota intestinal), seguido de randomização para tratamentos de 14 dias com aumento na ingestão de fibras (grupo F) ou aumento de fibras acompanhado da ingestão de 2 litros de água por dia (grupo FA), repetindo-se a aferição das variáveis ao final. Resultados: Dezenove participantes foram analisados, sendo 10 no grupo F e 9 no grupo FA. A maioria dos participantes (68,4%) desenvolveu um ou mais sintomas abdominais, particularmente os do grupo F, em comparação ao FA (90% vs. 44%; P = 0,034). Participantes de ambos os grupos aumentaram significativamente o número de evacuações/semana (grupo F: 6,8 antes vs. 8,8 depois; grupo FA: 8,4 antes vs. 9,9 depois; P < 0,05), enquanto que apenas os participantes do grupo FA apresentaram aumento no peso bruto fecal (71,5 g vs. 126 g; P = 0,020) e no percentual de água nas fezes (74,5% vs. 78,4%; P = 0,038). A qualidade de vida mensurada pelo WHOQOL-Bref não diferiu em nenhuma intervenção. O tratamento com FA aumentou significativamente a população de bactérias do gênero Bacteroides e Prevotella, Faecalibacterium prausnitzii e Bifidobacteriums sp, enquanto que ambos FA e F reduziram a contagem das bactérias do gênero Desulfofibrio. Conclusões: Em voluntários sadios, o aumento no consumo de fibras e água melhorou o hábito intestinal, mas foi acompanhado de sintomas abdominais, particularmente quando o aumento na ingestão de fibras não foi acompanhado por aumento no consumo de água. O efeito na microbiota também foi superior no grupo tratado com fibra e água. / Background and aims: Intestinal physiology can be influenced by changes in fiber and water intake. This simple concept supports the recommendation of increasing fiber and water ingestion for treatment of bowel constipation. The aim of our study was to test whether such recommendation is true in healthy volunteers. Methods: In this open label clinical trial, 20 healthy participants had their basal characteristics determined (diet, bowel function, quality of life and intestinal microbiota), followed by randomization for 14 days treatment with increased fiber consumption (group F) or increased fiber and water intake (group FW), with reassessment of the variables at the end. Results: Nineteen participants were analyzed (10 F and 9 FW). The majority of them (68.4%) developed one or more abdominal symptoms during the treatments, particularly the group F as compared to FW (90% vs. 44%; P = 0.034). Both groups showed increased number of evacuations per week (group F: 6.8 before vs. 8.8 after; group FA: 8.4 vs. 9.9; P < 0.05), whereas group FW presented an increase in both fecal weight (71.5 g vs. 126 g; P = 0.020) and water percentage in feces (74.5% vs. 78.4%; P = 0.038). Quality of life measured by WHOQOL-Bref did not differ in any intervention. Participants receiving FW had a significant increase in bacteria from the Bacteroides and Prevotella genus, Faecalibacterium prausnitzii and Bifidobacterium, whereas both FW and F had a reduced number of Desulfofibrio. Conclusions: In healthy volunteers, a higher intake of fiber and water improved the bowel function but was accompanied by abdominal symptoms, particularly when the dietary fiber was introduced without changes in water intake. The effect on fecal microbiota was superior in participants treated with fiber and water.
480

Efeito das drogas Dexametasona e Azatioprina na viabilidade, morfologia e comportamento migratório de células-tronco mesenquimais

Schneider, Natália January 2014 (has links)
Glicocorticoides e outras drogas imunossupressoras são comumente utilizados para o tratamento de condições inflamatórias, como as Doenças Inflamatórias Intestinais (DIIs). Apesar dos avanços na terapia medicamentosa, a remissão da doença ainda é difícil de ser mantida. Devido às suas propriedades imunomodulatórias, as Células-Tronco Mesenquimais (MSCs – Mesenchymal Stem Cells) têm emergido como reguladoras da resposta imune, e sua viabilidade e propriedades migratórias são essenciais para o sucesso da terapia celular. Entretanto, pouco se conhece sobre os efeitos das drogas convencionalmente utilizadas no tratamento das DIIs no comportamento das MSCs. Portanto, o objetivo deste estudo foi avaliar a viabilidade, a morfometria nuclear, a polaridade celular, a distribuição da actina-F e da FAK (Focal Adhesion Kinase), e o comportamento migratório das MSCs na presença das drogas Azatioprina (AZA) e Dexametasona (DEXA). As células foram isoladas de membranas coriônicas humanas e caracterizadas pela diferenciação em adipócitos e osteócitos, bem como pela expressão de um painel de marcadores de superfície. As MSCs foram previamente tratadas com AZA ou DEXA por 24h ou 7d nas concentrações de 1μM ou 10μM, respectivamente. Ambas as drogas não afetaram a viabilidade celular analisada por MTT (3-(4,5-dimethyltiazol-2-yl)-2,5- diphenyltetrazolium bromide) e morfometria nuclear. Entretanto, a análise do índice de polaridade resultou em uma morfologia mais alongada após o tratamento com AZA, enquanto células mais arredondadas foram observadas na presença de DEXA. Os filamentos de actina foram marcados por Rodamina-Faloidina e sua análise mostrou que a AZA preservou parcialmente a formação de lamelipódios e aumentou a presença de fibras de estresse ventrais, enquanto que a DEXA inibiu a formação de lamelipódios, evidenciou uma maior presença de fibras de estresse ventrais e diminuiu a estabilidade das protrusões de membrana, observadas em vídeo. Através da análise de microscopia de série temporal, foi observado que as células sob o efeito da AZA por 7d migraram por maiores distâncias e tiveram um aumento em sua velocidade de migração (24,35%; P < 0,05; n = 4), ao passo que a DEXA diminuiu a velocidade migratória em 24h e 7d (-28,69% e -25,37%, respectivamente; P < 0.05; n = 4) e diminuiu a distância alcançada pelas células. Em conclusão, nossos dados sugerem que as drogas AZA e DEXA podem afetar diferentemente a morfologia e o comportamento migratório das MSCs, possivelmente afetando o resultado da terapia celular. O protocolo de migração celular utilizado neste estudo foi estabelecido por nosso grupo de pesquisa, sendo que um artigo científico contendo todas as etapas do protocolo foi escrito para que outros laboratórios possam utilizá-lo de maneira simples e eficaz. / Glucocorticoids and other immunosuppressive drugs are commonly used to treat inflammatory disorders, such as Inflammatory Bowel Disease (IBD) and, despite few improvements, the remission of IBD is still difficult to maintain. Due to its immunomodulatory properties, Mesenchymal Stem Cells (MSCs) have emerged as regulators of immune response, and its viability and activation of migratory properties are essential for a successful cell therapy. However, little is known about the effects of immunosuppressant drugs used on IBD treatment on MSCs behavior. In this way, the aim of this study was to evaluate MSCs viability, nuclear morphometry, cell polarity, F-actin and FAK (Focal Adhesion Kinase) distribution and cell migration properties in the presence of the immunosuppressive drugs Azathioprine (AZA) or Dexamethasone (DEX). MSCs were isolated from human chorionic membranes and characterized through adipogenic and osteogenic differentiations, as well as a panel of surface markers. Cells were previously treated with AZA or DEX for 24 hrs or 7 days at 1μM and 10μM, respectively. Both drugs had no effects on cell viability analyzed through MTT (3-(4,5- dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide) and nuclear morphometry. However, polarity index analysis showed that AZA treatment induced a more elongated cell shape while a greater presence of rounded cells was observed under DEX exposure. F-actin was stained by Rhodamine-Phalloidin and showed that AZA could partially preserve lamellipodia formation and increase the presence of ventral actin stress fibers, while DEX inhibited lamellipodia formation and increased the presence of ventral actin stress fibers while decreasing protrusion stability, observed in video. Through time-lapse microscopy, it was observed that after 7 days of treatment, AZA improved cell the spatial trajectory (ST) and increased migration speed (24.35%, P < 0.05, n = 4) while DEX impaired ST and migration speed after 24 hrs and 7 days treatment (- 28.69% and -25.37%, respectively; P < 0.05, n = 4). In conclusion our data suggests these immunosuppressive drugs can differently affect MSCs morphology and migration capacity, possibly impacting the success of cell therapy. The migration protocol used in this study was successfully established by our group, leading to the writing of a protocol paper to facilitate the usage of this technique by other laboratories in a simple and efficient manner.

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