| 1. |
- Wagner, Michael, 1957-, et al.
(författare)
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Fecal markers of inflammation used as surrogate markers for treatment outcome in relapsing inflammatory bowel disease
- 2008
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Ingår i: World Journal of Gastroenterology. - : WJG Press. - 1007-9327 .- 2219-2840. ; 14:36, s. 5584-5589
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate fecal calprotectin (FC) as a surrogate marker for treatment outcome of a relapse of inflammatory bowel disease (IBD) and, secondly, to compare FC to fecal myeloperoxidase (MPO) and fecal eosinophil protein X (EPX). Methods: Thirty-eight patients with IBD, whereof twenty-seven with ulcerative colitis (UC) and 11 with Crohn´s disease (CD) were studied before treatment (inclusion), and after four and eight weeks of treatment. Treatment outcome, based on clinical activity and endoscopy in UC patients, and clinical activity in CD patients, were evaluated together with fecal samples analysed for FC with ELISA and MPO and EPX with RIA. Results: At inclusion 37/38 (97%) patients had elevated FC levels (>94.7 µg/g). At the end of the study 31/38 (82%) patients fulfilled predefined criteria of a complete response [UC 21/27 (78%); CD 10/11 (91%)]. Overall, a normalised FC level at the end of the study predicted a complete response in 100% whereas elevated FC level predicted noncomplete response in 30%. Normalised MPO or EPX levels predicted a complete response in 100% and 90%, respectively. However, elevated MPO or EPX levels predicted noncomplete response in 23% and 22%, respectively. Conclusion: A normalised FC level poses the potential to be used as a surrogate marker for successful treatment outcome in IBD patients, but cases with persistent elevated FC levels needs further evaluation. FC and MPO appears to discriminate better than EPX to treatment outcome in IBD.
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| 2. |
- Blom, Kristin, et al.
(författare)
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Eosinophil associated genes in the inflammatory bowel disease 4 region : Correlation to inflammatory bowel disease revealed
- 2012
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 18:44, s. 6409-6419
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP). METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5'-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP (R) system as described by the manufacturer. Statistical tests for calculations of results were chi(2) test, Fisher's exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant. RESULTS: The genotype frequency for males with UC and with an age of disease onset of >= 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject's genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29 /0,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of >= 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in mu g/10(6) eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes. CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.
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| 3. |
- Taha, Yesuf, et al.
(författare)
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Steroids reduce local inflammatory mediator secretion and mucosal permeability in collagenous colitis patients
- 2006
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 12:43, s. 7012-7018
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the effect of oral steroids upon clinical response and rectal mucosa secretion of eosinophil cationic protein (ECP), myeloperoxiclase (MPO), basic fibroblast growth factor (bFGF), vascular enclothelial growth factor (VEGF) and albumin in patients with collagenous colitis (CC). METHODS: A segmental perfusion technique was used to collect perfusates from rectum of CC patients once before and twice (one and four weeks) after the start of steroid treatment. Clinical data was monitored and ECP, MPO, bFGF, VEGF and albumin concentrations were analyzed by immunochernical methods in perfusates and in serum. RESULTS: Steroids reduced the number of bowel movements by more than five times within one week and all patients reported improved subjective wellbeing at wk 1 and 4. At the same time, the median concentrations of ECP, bFGF, VEGF and albumin in rectal perfusates decreased significantly. MPO values were above the detection limit in only 3 patients before treatment and in none during treatment. VEGF, bFGF, ECP and albumin concentrations correlated with each other with the exception of ECP and albumin. A decrease of serum ECP and VEGF concentrations was also seen even if the overtime reduction was not significant. CONCLUSION: Oral steroid treatment in CC patients induced a simultaneous reduction of bowel movements and rectal release of ECP, bFGF, VEGF and albumin, suggesting that these polypeptides and increased mucosal permeability are important components of the pathophysiology in collagenous colitis.
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