Made available in DSpace on 2014-06-11T19:32:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-05-30Bitstream added on 2014-06-13T20:03:08Z : No. of bitstreams: 1 kushima_h_dr_botib.pdf: 1089562 bytes, checksum: 1afece4aabc68a6b84aa6879f8e72585 (MD5) / A doença inflamatória intestinal (DII) corresponde a um conjunto de desordens crônicas inflamatórias intestinais, de etiologia ainda desconhecida, sendo a retocolite (RCU) e a doença de Crohn (DC) as duas doenças mais representativas e de maior importância clínica. Devido a pouca eficácia das terapias convencionais, muitos pacientes recorrem a métodos alternativos, como o uso de plantas medicinais. As espécies Davilla elliptica St. Hil e Davilla nitida (Vahl) Kubitzki (família Dilleniaceae) são plantas arbustivas comumente encontradas no Cerrado brasileiro. D. elliptica, conhecida como lixeirinha, é utilizada na medicina popular para o tratamento de afecções do trato gastrointestinal, como úlceras e gastrites, e também utilizado como antiinflamatório. D. nitida (cipó de fogo) apresenta um grande potencial para o tratamento de doenças do trato gastrointestinal, pois semelhante a D. elliptica, apresenta comprovada ação gastroprotetora e ambas possuem perfis fitoquímicos semelhantes, compostos basicamente de polifenóis. Os objetivos deste trabalho foram avaliar os efeitos preventivos e/ou curativos dos extratos metanólicos de D. elliptica (EDE) e D. nitida (EDN) em modelos experimentais de colite (agudo e crônico) induzidos pelo ácido trinitrobenzenosulfônico (TNBS) em ratos e os possíveis mecanismos decorrentes dessas ações farmacológicas. A partir dos resultados anteriormente obtidos da ação gastroprotetora de ambos os extratos, foram selecionadas as doses empregadas nos modelos experimentais de colite. Foi constatado que altas doses (500 mg/kg) de EDE e EDN administradas oralmente, promovem o agravamento das injúrias no cólon (aumento de 47 e 21% das lesões, respectivamente). Porém, ao avaliar os efeitos agudos de ambos os extratos no modelo de colite com doses menores (31.2, 62.5 e 125 mg/kg), ocorreram reduções significativas das áreas... / Inflammatory bowel disease (DII) represents a group of chronic inflammatory bowel disorders of unknown etiology, and ulcerative colitis (RCU) and Crohn's disease (DC) both diseases are most representative and important among the DII clinic. Because the conventional therapies ineffectiveness, many patients resort to alternative methods, such as the use of medicinal plants. The species Davilla elliptica St. Hil and Davilla nitida (Vahl) Kubitzki (family Dilleniaceae) are shrubs commonly found in the Brazilian Cerrado. D. elliptica, known as “lixeirinha”, is used in folk medicine for the gastrointestinal disorders treatment such as gastritis and ulcers and also used as antiinflammatory. D. nitida (“cipó de fogo”) has great potential to treat gastrointestinal diseases, thus similar to D. elliptica, has proven gastroprotective action and both have similar phytochemical profiles, composed primarily of polyphenols. Our objectives were to evaluate the preventive and/or healing effects of the D. elliptica (EDE) and D. nitida (EDN) methanolic extracts in the colite experimental models (acute and chronic) induced by trinitrobenzenesulfonic acid (TNBS) in rats and possible mechanisms resulting from these pharmacological actions. From the previous results of gastroprotective action of both extracts, we selected the doses used in experimental models of UC. It was found that high doses (500 mg / kg) of EDN and EDE administered orally, promoted the colon injury aggravation (lesion increasing of 47 and 21%, respectively). However, in assessing the acute effects of both extracts in the UC model at lower doses (31.2, 62.5 and 125 mg/kg), there were significant reductions in areas (for both extracts) and scores of the injuries (EDN only) promoted by TNBS. The colonic lesions reduction in the animals treated with EDE and EDN did not alter the weight/length parameter of colon and feed... (Complete abstract click electronic access below)

Orientador: Clélia Akiko Hiruma-Lima / Banca: Luiz Cláudio Di Stasi / Banca: Alessandra Gambero / Banca: Marcelo Aparecido da Silva / Banca: Noeli Pereira Rocha / Resumo: A doença inflamatória intestinal (DII) corresponde a um conjunto de desordens crônicas inflamatórias intestinais, de etiologia ainda desconhecida, sendo a retocolite (RCU) e a doença de Crohn (DC) as duas doenças mais representativas e de maior importância clínica. Devido a pouca eficácia das terapias convencionais, muitos pacientes recorrem a métodos alternativos, como o uso de plantas medicinais. As espécies Davilla elliptica St. Hil e Davilla nitida (Vahl) Kubitzki (família Dilleniaceae) são plantas arbustivas comumente encontradas no Cerrado brasileiro. D. elliptica, conhecida como lixeirinha, é utilizada na medicina popular para o tratamento de afecções do trato gastrointestinal, como úlceras e gastrites, e também utilizado como antiinflamatório. D. nitida (cipó de fogo) apresenta um grande potencial para o tratamento de doenças do trato gastrointestinal, pois semelhante a D. elliptica, apresenta comprovada ação gastroprotetora e ambas possuem perfis fitoquímicos semelhantes, compostos basicamente de polifenóis. Os objetivos deste trabalho foram avaliar os efeitos preventivos e/ou curativos dos extratos metanólicos de D. elliptica (EDE) e D. nitida (EDN) em modelos experimentais de colite (agudo e crônico) induzidos pelo ácido trinitrobenzenosulfônico (TNBS) em ratos e os possíveis mecanismos decorrentes dessas ações farmacológicas. A partir dos resultados anteriormente obtidos da ação gastroprotetora de ambos os extratos, foram selecionadas as doses empregadas nos modelos experimentais de colite. Foi constatado que altas doses (500 mg/kg) de EDE e EDN administradas oralmente, promovem o agravamento das injúrias no cólon (aumento de 47 e 21% das lesões, respectivamente). Porém, ao avaliar os efeitos agudos de ambos os extratos no modelo de colite com doses menores (31.2, 62.5 e 125 mg/kg), ocorreram reduções significativas das áreas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Inflammatory bowel disease (DII) represents a group of chronic inflammatory bowel disorders of unknown etiology, and ulcerative colitis (RCU) and Crohn's disease (DC) both diseases are most representative and important among the DII clinic. Because the conventional therapies ineffectiveness, many patients resort to alternative methods, such as the use of medicinal plants. The species Davilla elliptica St. Hil and Davilla nitida (Vahl) Kubitzki (family Dilleniaceae) are shrubs commonly found in the Brazilian Cerrado. D. elliptica, known as "lixeirinha", is used in folk medicine for the gastrointestinal disorders treatment such as gastritis and ulcers and also used as antiinflammatory. D. nitida ("cipó de fogo") has great potential to treat gastrointestinal diseases, thus similar to D. elliptica, has proven gastroprotective action and both have similar phytochemical profiles, composed primarily of polyphenols. Our objectives were to evaluate the preventive and/or healing effects of the D. elliptica (EDE) and D. nitida (EDN) methanolic extracts in the colite experimental models (acute and chronic) induced by trinitrobenzenesulfonic acid (TNBS) in rats and possible mechanisms resulting from these pharmacological actions. From the previous results of gastroprotective action of both extracts, we selected the doses used in experimental models of UC. It was found that high doses (500 mg / kg) of EDN and EDE administered orally, promoted the colon injury aggravation (lesion increasing of 47 and 21%, respectively). However, in assessing the acute effects of both extracts in the UC model at lower doses (31.2, 62.5 and 125 mg/kg), there were significant reductions in areas (for both extracts) and scores of the injuries (EDN only) promoted by TNBS. The colonic lesions reduction in the animals treated with EDE and EDN did not alter the weight/length parameter of colon and feed... (Complete abstract click electronic access below) / Doutor

A Doença de Crohn (CD) e a Colite Ulcerativa (UC) são as principais enfermidades componentes das Doenças Inflamatórias Intestinais (DII). Embora existam vários medicamentos atualmente empregados para atenuar a inflamação descontrolada no intestino, tratar as complicações ou prolongar os períodos de remissão clínica, não há, ainda, uma terapia que seja totalmente efetiva para estas doenças. Os glicocorticoides (GCs), anti-inflamatórios comumente usados nas DII, possuem eficácia limitada e mais da metade dos pacientes se tornam refratários ou dependentes da medicação. Por outro lado, as estatinas são conhecidas por possuírem propriedades pleiotrópicas e seu uso concomitante com os GCs tem gerado boas perspectivas em várias doenças autoimunes e inflamatórias, inclusive nas DII. Apesar de já existirem indicativos de melhora de pacientes com DII pela utilização combinada destas drogas, ainda há escassez de dados que mostrem as alterações causadas no sistema imunológico. Assim, o objetivo desse trabalho foi avaliar os efeitos imunomoduladores do uso concomitante de GCs e estatinas na colite experimental induzida por dextran sulfato de sódio (DSS) em camundongos C57BL/6. Os resultados mostraram que o uso contínuo de GCs (dexametasona - DX), associados ou não a estatinas (atorvastatina - ATO), não alterou o curso da doença e antecipou a morte dos camundongos, enquanto que o oposto foi observado com o uso isolado de ATO. Tratamentos em curto prazo (3 doses) contendo ATO (isolada ou associada à DX) causaram melhora clínica e histológica dos animais doentes, diminuíram o número de leucócitos circulantes (principalmente monócitos) e de células mononucleares na lâmina própria (LP), a frequência de células CD11b+ na LP, a frequência de células dendríticas (DCs) CD11b+CD11c+ e CD11b-CD11c+ no baço e a frequência de células CD4+ produtoras de IFN- nos linfonodos mesentéricos (LNM). Entretanto, ambos os esquemas terapêuticos aumentaram a frequência de linfócitos T CD8+ no baço e LNM. Ainda, as terapias inibiram a proliferação de esplenócitos tratados in vitro, diminuíram a síntese de IL-6 e, quando em baixas concentrações, aumentaram a produção de IL-10. Diferencialmente, o tratamento combinado pareceu exercer os efeitos acima descritos de modo mais pronunciado do que o uso isolado de estatina. Adicionalmente, diminuiu os níveis de expressão de RNAm das citocinas IL-1, IL-17 e IFN- no local da inflamação, reduziu o número de linfócitos circulantes, de leucócitos no baço e LNM e de linfócitos T CD4+ nos LNM, além de ter aumentado a frequência de DCs CD11b-CD11c+ na LP e a concentração de Fas-L no intestino grosso. Considerando o uso em curto prazo com ATO isolada, foi observado aumento da frequência de DCs CD11b-CD11c+ nos LNM e de células Natural killer (NK) no baço dos camundongos doentes e diminuição dos níveis de expressão de RNAm de PPAR- no intestino grosso. O uso isolado de DX em curto prazo melhorou os aspectos histológicos, diminuiu o número de macrófagos e os níveis de IFN- no cólon, diminuiu o número de leucócitos circulantes (principalmente linfócitos), aumentou a frequência de células CD11b+ no baço e a síntese de IL-10 por esplenócitos ex vivo. Apesar da frequência de células T reguladoras (Treg) e da susceptibilidade dos esplenócitos à sinais reguladores não terem sido modificados após os diferentes tratamentos, nossos resultados sugerem que as estatinas usadas isoladamente preservaram a resposta inflamatória do organismo de modo eficiente e controlado, enquanto que o uso associado das drogas causou a imunossupressão dos animais doentes, contribuindo para as complicações clínicas decorrentes da colite experimental induzida por DSS. / Crohn\'s disease (CD) and Ulcerative colitis (UC) are the main conditions that comprise the Inflammatory Bowel Diseases (IBD). The conventional drug therapies for IBD aim to attenuate the uncontrolled inflammation in the intestinal mucosa, to treat the complications and to extend clinical remission. However, all available drugs have unpredictable or limited effects. Glucocorticoids (GCs) are commonly anti-inflammatory drugs, which are associated to refractoriness and/or dependence in over half of IBD patients. On the other hand, statins have pleiotropic properties and the concomitant use with GCs has shown good prospects in several autoimmune and inflammatory diseases, including IBD. Despite the putative clinical improvement after combined use of GCs and statins in IBD, there is a lack of data indicating their additive effects on the immune system. Therefore, the purpose of this study was to evaluate the immune modulatory effects of the concomitant use of statins and GCs in experimental colitis induced by dextran sulfate sodium (DSS). The results showed that long-term use of GCs (dexamethasone - DX), alone or associated to statins (atorvastatin - ATO), did not improve the clinical signs and increased the death rates of C57BL/6 mice exposed to DSS, while the opposite was observed after treatment with statins alone. Short-term use of ATO (3 doses), alone or associated to DX, improved the clinical signs and histological parameters in DSS-exposed mice, decreased the number of white blood cells (mainly monocytes), the number of mononuclear cells in the lamina propria (LP), the frequency of CD11b+ cells in the LP, the frequency of CD11b+CD11c+ and CD11b-CD11c+ dendritic cells (DCs) in the spleen and the frequency of IFN--producing CD4+ T cells in the mesenteric lymph nodes (MLN). However, ATO alone or associated to DX lead to increased CD8+ T lymphocytes in the spleen and MLN. Moreover, both therapies containing ATO inhibited the proliferation of in vitro-treated splenocytes, besides decreasing IL-6 and increasing IL-10 synthesis. Differentially, the association of drugs led to a more pronounced effects over the changes mentioned above than the single use of statin and additionally decreased IL-1, IL-17 and IFN- mRNA expression levels at the intestinal tissue, the number of circulating lymphocytes, the number of leukocytes in spleen and MLN and the frequency of CD4+ T lymphocytes in the MLN. In addition, statins and GCs increased the frequency of CD11b-CD11c+ DCs in LP and the Fas-L concentrations in the large intestine. Considering the short-term use of ATO there was increased frequency of CD11b-CD11c+ DCs in MLN, increased frequency of natural killer (NK) cells in the spleen and decreased mRNA expression of PPAR- in the large intestine. The short-term use of DX improved the histology parameters, decreased the number of macrophages and IFN- levels in the colon, reduced the number of circulating leukocytes (mainly lymphocytes), and increased the frequency of CD11b+ cells in spleen and IL-10 synthesis by ex vivo splenocytes. Finally, since both regulatory T cells (Treg) frequency and the splenocytes susceptibility to regulatory signals have not been modified after the different treatments, our findings suggest that single use of statins preserved an efficient and controlled inflammatory response, while the combined use of GCs and statins led to immunosuppression, which probably contributed to long-term clinical complications of DSS-induced colitis.

No description available.

A breakdown of intestinal homeostasis due to dysregulated immune responses against intestinal bacteria underlies the pathogenesis of inflammatory bowel disease (IBD) in genetically susceptible individuals. Amongst mucosal immune cells, innate lymphoid cells (ILCs) are a heterogeneous group of cells whose functions in pathogenic inflammatory processes in the intestine are beginning to emerge from experimental murine models. However, less is known about the role of ILCs in chronic intestinal inflammation in humans. In this thesis, human ILCs were examined in the context of IBD and potential mechanisms by which these cells may contribute to IBD pathogenesis were investigated. We identified phenotypically and functionally distinct ILC1, ILC2 and ILC3 populations in the human intestinal lamina propria and peripheral blood and found that ILCs enriched for expression of IL-17A and IFNγ accumulated in the inflamed intestine, potentially through increased in situ proliferation and chemokine-mediated recruitment from blood. Based on their in situ localization, we investigated potential functional interactions between ILCs and CD4+ T cells and found that a proportion of human ILCs in peripheral blood and the intestinal lamina propria expressed HLA-DR and co-stimulatory molecules. ILCs were capable of taking up and processing protein antigen at levels equivalent to B cells, but in contrast to monocytes, antigen-pulsed ILCs failed to activate antigen-specific memory CD4+ T cells in vitro. Reciprocal activation between ILCs and monocytes enhanced the antigen-presenting potential and bactericidal capacity of myeloid cells and induced upregulation of co-stimulatory ligand expression by ILCs. This innate activation loop resulted in an augmentation of CD4+ T cell activation. These findings extend our knowledge of the complex interactions between human ILCs and other key immune cell populations, and suggest mechanisms by which rare ILCs may contribute to the pathogenesis of IBD by augmenting myeloid cell and CD4+ T cell responses.

In recent years, the association between inflammatory bowel diseases (IBDs) and gut microbiota has been extensively studied in adults using post-treatment cohorts of patients. However, microbial composition and functional interplay between host genetics and microorganisms in newly diagnosed early IBD onset remain poorly defined. Using colonoscopic mucosal washes to collect mucosal-luminal microbiota from different intestinal locations, we studied the gut microbiome in a large number of children with either Crohn’s disease (CD) or ulcerative colitis (UC). Although no significant difference in the diversity was evident between the gut microbiota of IBD-affected and control children, the microbiome of IBD subjects is characterized by an increased abundance of potent hydrogen sulfide (H2S) producers and decreased abundance of beneficial butyrate producers. Microbiota and proteomic profiling revealed that the abundance of Atopobium parvulum, a potent H2S producer, was associated with increased CD severity and a concurrent reduction in the expression of the host H2S detoxification pathway. Gnotobiotic and conventionalized colitis-susceptible interleukin-10-deficient (Il-10-/-) mice showed that A. parvulum induces severe colitis, a phenotype requiring the presence of the gut microbiota. In addition, administration of bismuth, an H2S scavenger, prevented A. parvulum-induced colitis in Il-10-/- mice. Our findings have identified A. parvulum as a major mediator of inflammation severity. We also reveal an imbalance between the H2S production and detoxification in the gastrointestinal tract of pediatric IBD patients. Altogether, our findings provide new avenues for diagnostics as well as therapies to treat IBD.

INTRODUCTION: Reactive oxygen species are responsible for the mediation of physiologic and pathologic cellular responses. The tissue damage occurring in all inflammatory disorders, including that observed in patients with inflammatory bowel disease (IBD), is mediated by reactive oxygen species (ROS) generated and released by activated immunocompetent cells. When present in sufficient concentration, these oxidative ROS are toxic to both real or perceived infectious or allergic threats, as well as native tissues in the context of autoimmune disease. The diagnosis and interval assessment of patients with IBD currently rely on expensive and invasive procedures that create cost and logistic drawbacks for both patients and the larger health care system. Thus, there is a pressing need for the development of reliable, cost-effective, and noninvasive methods to better diagnose and manage patients with IBD. OBJECTIVES: The goal of this present study was to assess the relationship between disease activity and ambient oxidative state in the stool of patients with and without IBD. METHODS: Patients admitted to Boston Children’s Hospital (Boston, MA) were recruited and consented for participation in the study. Stool samples were collected, and the redox potential (mV) was assessed using three different redox status measuring systems. The samples were collected between November 2018 and March 2020. RESULTS: Data demonstrated that reliable measurements could be made of redox status in stool samples collected from patients with and without IBD. Data collected from patients with IBD displayed an inverse correlation between relative redox status and disease activity. CONCLUSION: The measurement of relative redox status in the stool of patients with and without IBD is a reliable tool for indicating clinical disease status. Furthermore, the initiation of an improved method for the collection and processing of stool samples from consented patients appears to increase study accrual and data collection. Data from this study can be used as the basis for future studies that assess the clinical impact of pharmacologic, lifestyle, and dietary approaches to managing fecal redox in patients with IBD.

BACKGROUND: Inflammatory Bowel Disease (IBD) is a collective term that refers to chronic inflammatory diseases involving the gastrointestinal (GI) tract. The most common forms of IBD include Crohn’s Disease (CD) and ulcerative colitis (UC). GOALS: The goal of this study is to compare baseline and one-year follow-up measures of anxiety, depression, and quality of life in children with newly diagnosed IBD. A secondary goal of this study is to determine if there are parallel changes in the psychologic parameters in the parents of these children over a similar one-year interval. METHODS: This prospective cohort study was conducted in the Center for Inflammatory Bowel Diseases at Boston Children’s Hospital (BCH). The parents and children with newly diagnosed IBD completed validated questionnaires about their disease at baseline (within six months of their diagnosis) and then again 12-18 months later. RESULTS: Baseline data were collected from 75 patients with IBD, and 15 of these patient/parent dyads have completed follow-up questionnaires. The incidence of anxiety and depression trended downwards after the first year, and overall quality of life trended upwards, indicating an improvement in a global state of adjustment. Measures of anxiety and depression, as well as the reported frequency and difficulty of adverse events, all decreased in parental responses after the first year. CONCLUSION: While a larger sample size is necessary to better assess changes in psychometrics over time, existing data suggests that parents manifest the most significant change in anxiety and depression over the course of the first year from diagnosis. Children appear to be less anxious and depressed at baseline. Further enrollment and data collection will permit a more definitive assessment of the relationship between patient and parent coping strategies. Ideally, the results of this ongoing study will determine if impaired parental coping lowers a patient’s quality of life, contributes to higher childhood anxiety and depression scores, and results in higher healthcare utilization.

BACKGROUND: Characterized as inflammation of the gastrointestinal tract, pediatric inflammatory bowel disease has become increasingly more prevalent throughout the world. Inflammatory bowel disease is chronic, and no definitive cure exists. Instead, patients aim to achieve remission from flair-ups. Adequate transition into adult gastrointestinal care has been shown to be critical for future patient outcomes. Hence, successful transition from pediatric to adult inflammatory bowel disease care plays an important role in maintaining patient wellbeing. Identifying factors that contribute to patient transition readiness may be able to improve the transition process. OBJECTIVE: To elucidate sociodemographic and disease related parameters that influence transition, synthesize models that can predict transition readiness, and make recommendations to improve the process. METHODS: As part of a larger quality improvement project conducted by Massachusetts General Hospital for Children, 274 patients with inflammatory bowel disease ranging from ages 12 to 27 were enrolled between June 2019 and October 2020. Sociodemographic information was gathered via chart review. The Abbreviated Pediatric Crohn’s Disease Activity Index, Disease Activity Index Score, and Physician Global Assessment were completed by patients and physicians to assess disease severity. Patients also completed PROMIS questionnaires to assess anxiety, depression, sleep disturbance and impairment. Patients completed the Transition Readiness Assessment Questionnaire to gauge transition readiness. Bivariate analyses were conducted to elucidate the relationships between sociodemographic information, disease related parameters, and transition readiness. Multivariate regressions were conducted to synthesize models aimed at predicting transition readiness. RESULTS: Females had significantly worse disease severity, mental health, and sleep quality compared to males. Poor sleep quality had a significant relationship with disease severity and mental health status. Females had significantly higher transition readiness scores compared to males. Older age had a significant relationship with greater transition readiness. More patient anxiety was significantly associated with weaker communication skills. Otherwise, no disease related parameters significantly correlated with transition readiness. Disease duration demonstrated a significant positive relationship with transition readiness, particularly for patients diagnosed between the ages of 10 – 17. Models synthesized to predict transition readiness demonstrated substantial variability in predictive value. CONCLUSION: Transitioning from pediatric to adult inflammatory bowel disease care is a complex process. Future research should be aimed at elucidating discrepancies in transition readiness between genders, and further understanding the role disease duration plays in the transition process. Providers should work towards incorporating structured transition programs and improving patients’ disease-related knowledge, as well as patient familiarity with logistical aspects of the current US healthcare system. / 2023-11-09T00:00:00Z

BACKGROUND: Patients who have been diagnosed with Inflammatory Bowel Disease (IBD) present with increased risk of deficient vitamin D levels. Previous studies have demonstrated that these IBD patients who live in areas with lack of sun exposure are especially susceptible to becoming vitamin D deficient. Studies have also shown that the standard vitamin D dosing protocols have not proven effective in consistently improving vitamin D status. This failure is likely related to a combination of under-dosing and patient noncompliance. Vitamin D sufficiency is essential in the maintenance of both skeletal health and the immune system in children and adolescents. OBJECTIVES: The primary aim of this study is to investigate the safety and efficacy of administering an interval, high dose oral vitamin D supplementation in pediatric patients with IBD treated with Remicade. A secondary aim is to study the association between changes in serum 25OHD (25-hydroxyvitamin D3) levels and clinical and biochemical markers of IBD. The findings from this study will provide preliminary data for future studies using serial measurements of serum 25OHD levels to better articulate the optimal dosage for interval vitamin D supplementation in pediatric patients with IBD. METHODS: We identified and screened pediatric patients with IBD at Boston Children’s Hospital (BCH) with vitamin D deficiency (serum 25OHD level < 30 ng/mL). Vitamin D dosing was determined by a patient’s Remicade interval. Patients received either 50,000 international units (IU) of vitamin D3 (every 4-5 weeks) or 100,000 IU of vitamin D3 (every 6-8 weeks), concurrent with their Remicade infusion interval. Longitudinal data, including anthropomorphic measurements, serum chemistry labs, spot urine calcium to creatinine ratios, quality of life metrics, and surveys gauging dietary vitamin D intake and sunlight exposure, were collected throughout the study. RESULTS: Baseline vitamin D status in the 60 enrolled patients did not differ by gender, dosing group, diet, or diagnosis (Crohn disease, ulcerative colitis, or indeterminate colitis). Of the 57 patients for whom baseline and final serum 25OHD levels were available, there was a significant increase in total serum 25OHD levels from 22.53 ± 4.65 ng/mL to 29.91 ± 6.60 ng/mL, respectively. Similarly, increases in mean serum 25OHD levels were noted in both dosing formats and disease groups. Interestingly, there was no significant parallel impact of increased 25OHD levels on either disease activity or quality of life. There were no significant changes in serum calcium, phosphorous, and creatinine levels in response to changes in 25OHD levels. There were no reports of significant adverse events related to vitamin D supplementation. CONCLUSION: High dose, interval vitamin D supplementation improved vitamin D status from baseline in a majority of studied pediatric patients with IBD. The data suggest that this type of interval, high dose format is likely more effective than more traditionally once-daily dosing. Further studies are necessary to determine the optimal dosage regimens optimal in further increasing vitamin D status and to assess for its impact on clinical management.