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Implementation of high-dose interval vitamin D supplementation in patients with inflammatory bowel disease receiving infliximab or vedolizumabLavoie, Ashley 29 February 2024 (has links)
BACKGROUND: Vitamin D deficiency and insufficiency are rising healthcare concerns in the United States (US) and worldwide. The latest data collected by the National Health and Nutrition Examination Surveys (NHANES) between 2002-2006 showed that approximately one third of Americans over one-year-old were vitamin D deficient (serum 25-hydroxy vitamin D (25-OHD) < 12 ng/mL) or insufficient (serum 25-OHD < 20 ng/mL) (Looker et al., 2011). Environmental exposures, acute or chronic disease, and genetics can exacerbate vitamin D deficiency. People with malabsorptive disorders such as Inflammatory Bowel Disease (IBD) are at an even greater risk of becoming vitamin D deficient. Pediatric patients with IBD are particularly vulnerable to the short and long-term effects of vitamin D deficiency, given the prominent role played by this agent on skeletal development.
More recent data have demonstrated that vitamin D also plays an important role in maintaining and regulating the immune system. For this reason, investigators have been interested in a better understanding of the relationship between vitamin D and inflammation. Vitamin D may prove to be an important adjunct therapy for people suffering from IBD and other autoinflammatory diseases.
OBJECTIVES: Many patients and medical providers understand the importance that vitamin D has in a growing child’s skeletal development. However, compliance with daily supplementation remains low. The design of this study allows patients to receive high-dose vitamin D supplementation during scheduled biologic infusions. The goal is to assess the safety and efficacy of high-dose interval vitamin D therapy. The secondary goal of this study will be to determine if optimal vitamin D levels impact the inflammation observed in the gastrointestinal (GI) tract of patients with IBD.
METHODS: 60 patients with IBD, between 5-25 years of age, who received regularly scheduled infliximab or vedolizumab infusions, and had serum 25-OHD levels below 30 ng/mL were recruited for the study. These patients were screened for the exclusion criteria, including underlying liver or kidney disease. Enrolled participants were given eight high-dose oral vitamin D3 supplements during scheduled infliximab or vedolizumab infusions for 8-16 months. Serum 25-OHD levels, urine calcium and creatinine levels, and research blood samples were collected at baseline, midpoint, and final visits. Questionnaires were also dispensed to patients to measure quality of life (QoL). This data was collected and analyzed to assess the safety and efficacy of high-dose interval vitamin D supplementation in pediatric patients with IBD.
RESULTS: The data from this study showed statistical significance in the change of serum-25OHD level from baseline to midpoint and final visits. The mean increase from baseline to midpoint was 15.71±10.1 ng/mL for the 30 participants who had completed 3 study doses (2,500 mCg or 5,000 mCg) (mean±95% CI). The mean increase from baseline to final visit was 18.1±11.67 ng/mL for the 19 participants who completed all 7 study doses (2,500 mCg or 5,000 mCg) (mean±95% CI). A single factor ANOVA test confirmed statistical significance with p < 0.0001. Urine calcium and creatinine levels did not have a statistically significant change from baseline to final visit for the 12 participants who had completed both samples. Lastly, IMPACT-III QoL scores were not significantly different from baseline. However, there was an overall increase in the mean scores in all 6 subcategories of the survey. As more participants complete the study, the statistical significance and the validity of results will likely be strengthened.
CONCLUSION: High-dose interval vitamin D supplementation was a safe and effective way to achieve serum 25-OHD levels to an optimal range (i.e., 40-60 ng/mL) in pediatric patients and young adult patients with IBD. The data suggests that three doses of high-dose vitamin D may be sufficient to bring levels to an optimal and stable plateau. Patient compliance with supplementation was 100% in this study, because of provider-observed ingestion of vitamin D. Patients also noted that this was their preferred method of supplementation. The safety and efficacy results of this study serve as a framework for developing a more standard approach to vitamin D supplementation for our patients with IBD. Future studies may benefit from expanding this method of delivery to patients who have other inflammatory diseases that require both regular oral vitamin D therapy and in person visits for treatments (i.e., intravenous (IV) medication).
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Prevalence of Oral Lesions in Patients with Inflammatory Bowel DiseaseKiyani, Amber 19 November 2014 (has links)
No description available.
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Role of macrophages and eosinophils in inflammatory bowel diseasesWaddell, Amanda B. 20 April 2012 (has links)
No description available.
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Does in vivo exposure to perfluorooctanesulfonicacid induce an altered colonic barrier function inmice?Laar, Hanna-Dalia January 2022 (has links)
Background: Several environmental risk factors have been implicated in the pathogenesis ofinflammatory bowel disease (IBD) and might cause an altered barrier function, a hallmark ofIBD. Recent evidence suggests that patients with late-onset ulcerative colitis (UC) have anincreased serum level of perfluoroalkyl substances (PFAS), one of the major chemical groupscontaminating our diet. A potential route via which PFAS might contribute to the disease is bydisrupting the intestinal barrier. However, whether intake of PFAS dose induce an increasedintestinal permeability is still unknown. Aim: The aim of the thesis is to investigate the effect of in vivo exposure toperfluorooctanesulfonic acid (PFOA) in mice on colon barrier function. The hypothesis is thatlong time exposure to PFOA contributes to the development of late-onset ulcerative colitis bydisrupting the intestinal barrier. Methods: This controlled laboratory study used 7 mice exposed to PFOA in vivo via thedrinking water for 3 weeks and a control group of 9 mice for reference. Colon tissue from themice were excised for assessing intestinal permeability using the Ussing chamber method.FITCH-dextran was used as a macromolecular probe in the Ussing chamber to investigate themucosal-serosal flux across the intestinal mucosa to see macromolecular permeability andelectrophysiological parameters were assessed to investigate tight junction permeability,stimulated secretory response to Carbachol and active ion transport. Results: Although there were no statistically significant results between the PFOA treated groupand the control group, a trend of increased secretory response to Carbachol was observed in thePFOA group compared to the controls. Conclusion: The study demonstrates that in vivo exposure to PFOA does not induce an alteredintestinal barrier in terms of electrophysiological parameters and macromolecular flux. Futureexperiments are needed with a larger population and potentially genetically predisposed mice.Key
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DESIGN, SYNTHESIS, AND PRELIMINARY EVALUATION OF GAMMA-BUTYROLACTONE-BASED 5-HT7 LIGANDSGiratallah, Haidy January 2018 (has links)
Inflammatory bowel disease (IBD) is a serious, complex disease that is challenging to treat effectively and affects over 5 million people globally. Current treatment goals for both subtypes of IBD, Ulcerative Colitis (UC) and Crohn Disease (CD), focus on attaining and maintaining remission through anti-inflammatory agents, immunomodulators, or biologics. In spite of these treatments, more than 25% of patients require devastating surgical removal of part of their colon due to severe inflammation. Recent advances in our understanding of serotonergic effects beyond the central nervous system (CNS) provide encouragement for IBD treatment. The newest member of serotonin receptor family, the 5-HT7 subtype, is involved in the release of pro-inflammatory cytokines following stimulation by serotonin in the gastrointestinal tract (GIT). Khan et al have shown that inflammation associated with the DSS and DNBS mouse models of IBD is significantly attenuated in knock-out mice lacking the 5-HT7 receptor or mice treated with 5-HT7 selective antagonists. Previously reported 5-HT7 receptor antagonists (e.g., SB-269970) readily crosses the blood brain barrier (BBB) and are therefore not good choices for IBD treatments. Our group has identified a novel series of arylpiperazinyl lactones with high affinity and excellent selectivity for the 5-HT7. The aim of this project is to design, synthesize, and characterize new gamma-butyrolactone-based 5-HT7 ligands with high affinity, good selectively, acceptable drug-like properties, with limited access to the CNS. A total of 18 compounds were successfully synthesized and evaluated as potential new lead compounds for the treatment of IBD. / Pharmaceutical Sciences
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Livet som kroniskt sjuk : Unga kvinnors erfarenheter av att leva med en inflammatorisk tarmsjukdom. En kvalitativ studie av bloggar / Life as chronically ill : Young women’s experiences of living with an inflammatory bowel disease. A qualitative study of blogsJohansson, Amanda, Modin, Johanna January 2016 (has links)
Bakgrund: Majoriteten av de som drabbas av inflammatorisk tarmsjukdom är kvinnor. Att drabbas vid ung ålder kan öka problematiken. Det finns luckor i forskningen om de psykosociala faktorernas inverkan. Kronisk sjukdom skapar ofta lidande och för att kunna hantera det på ett värdigt sätt krävs kunskap och förståelse. Patienternas erfarenheter om sin sjukdom genererar en bättre inblick och ökad förståelse för sjuksköterskan. Kunskapen hjälper sjuksköterskor att erbjuda god vård för att patienten ska kunna uppleva en så bra livskvalité som möjligt. Syfte: Syftet med denna studie var att belysa unga kvinnors erfarenheter av att leva med en kronisk inflammatorisk tarmsjukdom. Metod: Datamaterialet analyserade med kvalitativ innehållsanalys. Data samlades genom 10 bloggar. Resultat: Ur analysen framträdde fyra kategorier: Vardagen begränsas, Lära sig leva med sjukdom, Kosten styr, Nöjda trots en bristande sjukhusorganisation och åtta underkategorier. Konklusion: Sjuksköterskans ökade kunskap och förståelse kring unga kvinnors erfarenheter av att leva med inflammatorisk tarmsjukdom är av stor vikt för att kunna erbjuda en god och individanpassad omvårdnad. Sjuksköterskans förståelse för patienten bidrar även till en stärkt vårdrelation och sjuksköterskan kan då ge den stöttning patienten efterfrågar.
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Erfarenheter av att leva med en livslång tarmsjukdom : En litteraturöversikt / Experiences of living with a life-long bowel disease : A literature reviewKarin, Pettersson, Bodemark Korkkinen, Marthina January 2014 (has links)
Bakgrund: IBD är ett samlingsnamn för de livslånga mag-och tarmsjukdomarna Crohns sjukdom och ulcerös kolit och karaktäriseras av perioder med remission och skov. Under ett skov befinner sig personen i ett utsatt läge vilket ställer stora krav på omvårdnaden där sjuksköterskans främsta uppgift är att lindra lidande och främja hälsa och att leva med sjukdomen kan påverka den upplevda hälsan. Syfte: Syftet med litteraturöversikten var att beskriva upplevelsen av att leva med den livslånga mag- och tarmsjukdomen IBD. Metod: I litteraturöversikten användes tio vetenskapliga studier med kvalitativ ansats. Studierna söktes med relevanta sökord i avsikt att besvara översiktens syfte. Utifrån studiernas resultat utformades fyra huvudkategorier. Resultat: Resultatet i översikten presenterades under fyra huvudkategorier; begränsningar i det sociala livet, värdefulla strategier i önskan att skapa en kontrollerbar vardag, känslomässig påverkan och upplevelser av möten med sjukvården. Diskussion: Upplevelsen av att leva med IBD medförde omställningar och begränsningar för personerna i vardagen. Detta diskuteras utifrån Erikssons (1994) teori om den lidande människan, utifrån litteraturöversiktens bakgrund och utifrån nya artiklar. / Background: IBD is a collective term for the life-long gastrointestinal diseases Crohn´s disease and ulcerative colitis and is characterized by periods of remission and relapse. During a relapse the person is in a vulnerable position which places great demands on nursing where the nurse´s primary task is to alleviate suffering and promote health and living with the disease can affect the perceived health. Aim: The aim of the literature review was to describe the experience of living with the life-long gastrointestinal disease IBD. Method: The literature review was based upon ten scientific studies with qualitative approach. The studies were searched with relevant keywords in order to answer the purpose of the review. The results of the studies were designed under four main themes. Results: The results of the survey were presented under four main themes; limitations in social life, valuable strategies in the desire to create a controllable living, emotional impact and experiences of encounters with health care. Discussions: The experience of living with IBD resulted in changes and limitations of the people in everyday life. This was discussed on the basis of Eriksson's (1994) theory of the suffering human being, based on the background of the literature review and new articles.
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Role of the hedgehog signalling pathway in inflammatory bowel diseaseLees, Charles William January 2009 (has links)
Introduction. The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are common in Western Europe (200-400 cases /100,000) and associated with substantial morbidity, although mortality is now low. There is presently a great unmet need for novel therapeutics in IBD as present agents are limited by lack of efficacy, toxicity and poor patient acceptance. Recent findings from genome-wide association studies (GWAS) have characterised the genetic architecture of CD and UC. Defects in innate and adaptive immunity have been clearly established, and substantial novel insights into disease pathogenesis have been gained. Over 30 genes / loci are now associated with CD; a number of these, along with a few specific loci, are also associated with UC. The hedgehog (HH) signalling pathway is critical to gastrointestinal development and plays key roles in intestinal and immune homeostasis. Furthermore, in addition to well described roles in tumorigenesis, it is evident that recapitulation of embryonic HH signals play critical roles in response to acute and chronic inflammatory challenge in diverse tissues. Aims. The main aims of the work presented in this thesis were to characterise the expression of key HH signalling components in the healthy and inflamed human intestine, establish whether germline variation in HH genes is associated with IBD and describe the in vitro responses of intestinal epithelial cells to pathogen associated molecular patterns. The WNT pathway, antagonised by HH in the intestine, and two HH target genes (NKX2.3 and CCL20) were also analysed for evidence of association with IBD. Methods. Expression of HH and WNT signalling components was described by immunohistochemistry and microarray analysis in healthy controls (HC), CD, UC, and non- IBD inflamed terminal ileal and colonic samples. Gene-wide haplotype-tagging studies were performed for GLI1 in Scottish, English and Swedish CD and UC, and Scottish early-onset colo-rectal cancer, IHH in Scottish IBD, NKX2.3 in Scottish and UK IBD, and CCL20 in Scottish, Swedish and Japanese IBD. Evidence for association of all HH (n=13) and WNT (n=27) signalling genes in CD was established by analysis of UK GWAS data and metaanalysis from UK, French/Belgium and N American studies. The effect of lipopolysaccharide (LPS) and muramyl dipeptide (MDP) on HH signalling was assessed in colonic epithelial cells (SW480). The effect of HH pathway agonists and antagonists on NFκB activity and cytokine expression was analysed in SW480 cells and peripheral blood mononuclear cells (HC and IBD patients) in vitro. Results. The expression of HH pathway ligand is present in the intestinal epithelium and the pathway response network in the lamina propria demonstrating the paracrine nature of HH signalling in the intestine. Immunohistochemical studies and microarray analysis demonstrates that HH pathway activity is decreased in all forms of colonic inflammation studied in man. Variation in Glioma-associated oncogene homolog 1 (GLI1), a key HH transcription factor located at 12q13 (IBD2), was associated with IBD (p<0.0001), UC (p<0.0001) and to a lesser extent CD (p=0.03) in Scotland, a finding replicated in English IBD and UC. This association was attributed to a non-synonymous SNP (rs2228226C→G) with pools odds ratio of 1.194 in meta-analysis of over 5000 individuals from Scotland, England and Sweden (p=0.0002). There was association of this SNP with early-onset colorectal cancer, but of borderline significance (p=0.05). The variant protein (Q1100E) is 50% less active than wild-type protein in vitro. IHH was not associated with CD or UC. Preliminary evidence was produced for association at SUFU (10q24; p=0.005), a GLI1- binding protein, and at the WNT3 / WNT9B locus (17q21; p=0.0005). MDP stimulation of colonic epithelial cells decreased HH pathway activity. Exogenous HH increased expression of CCL20. CCL20 promoter polymorphisms were associated with UC in Japanese patients (p=0.018) but not in Scotland or Sweden. NKX2.3 was associated with IBD in Scotland (UC>CD), but there was insufficient power for fine-mapping of causative variants. Conclusions. Multiple lines of evidence presented here demonstrate that the HH signalling pathway is involved in IBD pathogenesis. In key complementary in vivo studies (conceived by CWL; conducted in collaboration with the Gumucio lab in Ann Arbor) we have demonstrated that Gli1+/- mice develop early, severe colitis with high mortality in response to acute inflammatory challenge. Furthermore, lamina propria antigen presenting cells are identified as the key HH target cells. With HH agonists and antagonists in extensive preclinical and early clinical testing, these studies have real potential to translate into novel therapeutics for patients with IBD.
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Defence capabilities of human intestinal epithelial cellsFahlgren, Anna January 2003 (has links)
The epithelial cells lining the intestinal mucosa separate the underlying tissue from components of the intestinal lumen. Innate immunity mediated by intestinal epithelial cells (IECs) provides rapid protective functions against microorganisms. Innate immunity also participates in orchestrating adaptive immunity. Key components in innate defence are defensins. To study the production of defensins and how it is affected by intestinal inflammation IECs were isolated from the small and large intestines of patients suffering from ulcerative colitis (UC), Crohn´s disease (MbC), celiac disease (CD), and from controls, and analyzed by quantitative RT-PCR (qRT-PCR) and immunoflow cytometry. Defensin expressing cells were also studied by in situ hybridization and immunohistochemistry. Normally, only small intestinal Paneth cells express human α-defensin 5 (HD-5) and HD-6. In UC colon IECs, HD-5, HD-6, and lysozyme mRNAs were expressed at high levels. In Crohn´s colitis colon the levels of HD-5 and lysozyme mRNAs were also increased although not to the same extent as in UC. No increase was detected in MbC with ileal localization. Metaplastic Paneth cell differentiation in UC colon was primarily responsible for the expression of the antimicrobial components. Human β-defensin 1 (hBD-1) mRNA was more abundant in large than in small intestine of controls, and remained unchanged in UC and MbC. hBD-2 mRNA was barely detectable in normal intestine and was induced in UC IECs but not in MbC IECs. mRNAs for the recently discovered hBD-3 and hBD-4, were detected in IECs from both small and large intestine. Both hBD-3 and hBD-4 mRNA were significantly increased in IECs of UC patients but not of MbC patients. Bacteria and IL-1β induced hBD-2 but not hBD-1 mRNA in colon carcinoma cell lines. IFN-γ, but not TNF-α or IL-1β, augmented hBD-3 expression in these cells, while none of the agents induced hBD-4. High antimicrobial activity of IECs in UC may be a consequence of changes in the epithelial lining, which permit the adherence of microorganisms. Unexpectedly, in situ hybridization revealed expression of hBD-3 and hBD-4 mRNAs by numerous lamina propria cells in colonic tissue from UC patients. These cells were identified as plasma cells (CD138+). hBD-3 and hBD-4 mRNAs were also demonstrated in the plasmacytoma cell line U266. This is the first demonstration of defensins in plasma cells. The four prominent constituents of the intestinal glycocalyx, carcinoembryonic antigen (CEA), CEA cell adhesion molecule 1 (CEACAM1), CEACAM6 and CEACAM7 all seem to play a critical role in innate defence of the intestinal mucosa by trapping and expelling microorganisms at the epithelial surface. The inducibility of these molecules in colonic epithelial cell lines was analyzed by qRT-PCR, immunoflow cytometry, and immunoelectron microscopy. IFN-g but not bacteria, LPS, TNF-α, or IL-1β modified the expression of CEA, CEACAM1 and CEACAM6. None of these agents modified CEACAM7 expression. IFN-γ was shown to have two effects: a direct effect on CEACAM1 transcription, and promotion of cell differentiation resulting in increased CEA and CEACAM6 and decreased CEACAM7 expression. Scanning electron microscopy of jejunal biopsies from children with CD revealed the presence of rod shaped bacteria in ~40% of patients with active CD, but only in 2% of controls. 19% of treated CD patients still had adhering bacteria. Presence of bacteria is not due to lack of antimicrobial factors. In fact, HD-5, HD-6, and lysozyme mRNA levels were significantly increased in IECs of patients with active CD. hBD-1 and hBD-2 were unchanged. Lack of induction of hBD-2 may reflect disturbed signalling in IECs of CD patients. Analysis of CEA and CEACAM1 mRNA/protein expression showed no differences between CD patients and controls. Analysis of the mucins MUC2 and MUC3 revealed significantly increased MUC2 levels in active disease and unchanged MUC3. Immunohistochemistry demonstrated goblet cell metaplasia as well as staining of the apical portion of absorptive cells. Glycosylation status of proteins was studied by lectin histochemistry. Goblet cells in the mucosa of CD patients were stained by the lectin UEAI. This was not seen in controls. The lectin PNA stained the glycocalyx of controls but not that of CD patients. Thus, unique carbohydrate structures of the glycocalyx/mucous layer are likely discriminating features of CD patients and may allow bacterial binding. We conclude that the intestinal epithelium is heavily involved in the innate defence of the mucosa and that its reactive pattern is affected by intestinal inflammation. Keywords: human intestinal mucosa; epithelial cells; innate immunity; defensin; ulcerative colitis; Crohn´s disease; celiac disease; glycoαcalyx; mucin
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Klinische Studie zur möglichen Assoziation von Parodontitis und chronisch entzündlichen Darmerkrankungen - Ergebnisse zahnbezogener und parodontologischer Parameter / Clinical study of possible association between periodontitis and chronic bowel disease - results of dental and periodontal parametersLeuschner, Constanze 11 August 2016 (has links)
No description available.
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