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Oral immunoglobulin treatment improved intestinal permeability in children with active Crohn's disease.
Sundqvist, T, Stenhammar, L, Tjellström, B, Magnusson, KE, Forslund, T, Högberg, L
Acta paediatrica (Oslo, Norway : 1992). 2017;(4):647-653
Abstract
AIM: Crohn's disease (CD) is a chronic mucosal inflammation that affects the intestinal barrier function, for example, by altering the intestinal permeability. This pilot clinical study investigated the impact of oral human immunoglobulin (OHIG) treatment on permeability characteristics in children with active luminal Crohn's disease. METHODS The study was performed at the Department of Paediatrics, Norrköping Hospital, Sweden. Intestinal permeability was studied in three boys aged 13, 15 and 18 years with active CD, before and after a six-week treatment programme with OHIG, using different-sized polyethylene glycols as the test molecules. Three age- and sex-matched children with active CD treated with exclusive enteral nutrition (EEN) were also studied. RESULTS OHIG and EEN resulted in virtually similar reductions in the signs and symptoms of mucosal inflammation. However, OHIG, unlike EEN, appeared to normalise mucosal transfer leading to a normalisation of the maximum permeation of the small PEG molecules, as well as less restrictions of the larger PEG molecules. CONCLUSION Our study found that OHIG appeared to normalise the mucosal barrier. This suggests that it could offer a new additional and versatile treatment for paediatric CD patients, with a minimal risk of adverse effects.
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Exclusive Enteral Nutrition Does Not Normalize Gut Microflora Function in Pediatric Perianal Crohn Disease.
Tjellström, B, Stenhammar, L, Magnusson, KE, Midtvedt, T, Norin, E, Sundqvist, T, Högberg, L
Journal of pediatric gastroenterology and nutrition. 2015;(1):e4
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Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet.
Tapsas, D, Fälth-Magnusson, K, Högberg, L, Forslund, T, Sundqvist, T, Hollén, E
Scandinavian journal of gastroenterology. 2014;(11):1311-7
Abstract
OBJECTIVE Oats are accepted in the gluten-free diet (GFD) for children with celiac disease (CD). Some reports have indicated, however, that not all celiac patients tolerate oats. We have previously shown that some children still have high levels of urinary nitric oxide (NO) metabolites as markers of intestinal inflammation after 1 year on GFD with oats. In this study, we measured urinary NO metabolites in CD children who had been consuming oats-containing GFD for an extended, 2-6-year period, also taking into consideration ordinary consumption of nitrite/nitrate-rich foods close to the urine sampling. MATERIALS AND METHODS Morning urinary nitrite/nitrate concentrations were measured in 188 pediatric CD patients. A questionnaire was used to elucidate factors possibly affecting the urinary levels, for example, dietary factors, asthma, or urinary tract infection. RESULTS Oats were consumed by 89.4% of the patients for a median time of 3 years. The median nitrite/nitrate level was 980 μM. The majority (70.2%) who consumed oats had low levels of urinary nitrite/nitrate, that is, <1400 μM, while 29.8% demonstrated high levels, that is, >1400 μM. Nitrite/nitrate-rich foods did not significantly influence the urinary concentrations. CONCLUSION The urinary levels of NO metabolites revealed two subpopulations, one with high and one with low levels. The high levels could be possibly due to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). Nitrate-rich foods, asthma, or urinary tract infection did not affect the result. The elevated levels of NO metabolites could indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD.
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The effects of oats on the function of gut microflora in children with coeliac disease.
Tjellström, B, Stenhammar, L, Sundqvist, T, Fälth-Magnusson, K, Hollén, E, Magnusson, KE, Norin, E, Midtvedt, T, Högberg, L
Alimentary pharmacology & therapeutics. 2014;39(10):1156-60
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Plain language summary
Oats have been allowed in the gluten-free diet of patients with coeliac disease (CD), however concerns have been raised that they may not be safe to eat in a subset of these patients. Short chain fatty acids (SFCAs) have been identified as a marker of inflammation and gut metabolism. Recent studies have found that children with CD often have elevated SCFA levels, indicating a disturbance in the gut microflora. The aim of this study was to identify the effect of consuming oats in children recently diagnosed with CD by examining faecal SCFAs. 116 children were treated with or without oats in their gluten-free diet for one year to see if oats affect the gut microflora. The findings of this study indicate that the children consuming oats had higher faecal SCFA concentration after one year than those not consuming oats. Based on this study, the authors’ conclude that oats do affect the gut microflora metabolism and that some coeliac children consuming oats may develop gut mucosal inflammation, leading to further future complications.
Abstract
BACKGROUND Faecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated over recent decades by us and others suggest that wheat-free oats can safely be included in a gluten-free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs. AIM: To describe faecal SCFA patterns in children with newly diagnosed CD treated for 1 year with a GFD with or without oats. METHODS This report is part of a randomised, double-blind study on the effect of a GFD containing oats (GFD-oats) vs. a standard GFD (GFD-std). Faecal samples were received from 34 children in the GFD-oats group and 37 in the GFD-std group at initial diagnosis and/or after 1 year on a GFD. Faecal SCFAs were analysed. RESULTS The GFD-std group had a significantly lower total faecal SCFA concentration at 12 months compared with 0 months (P < 0.05). In contrast, total SCFA in the GFD-oats group remained high after 1 year on the GFD. The children in the GFD-oats group had significantly higher acetic acid (P < 0.05), n-butyric acid (P < 0.05) and total SCFA concentration (P < 0.01) after 1-year diet treatment compared to the GFD-std group. CONCLUSIONS Our results indicate that oats do affect the gut microflora function, and that some coeliac children receiving oats may develop gut mucosal inflammation, that may present a risk for future complications.
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Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis--a randomised trial.
Schön, T, Idh, J, Westman, A, Elias, D, Abate, E, Diro, E, Moges, F, Kassu, A, Ayele, B, Forslund, T, et al
Tuberculosis (Edinburgh, Scotland). 2011;(5):370-7
Abstract
In tuberculosis (TB), the production of nitric oxide (NO) is confirmed but its importance in host defense is debated. Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production. Smear positive TB patients from Gondar, Ethiopia (n = 180) were randomized to a food supplementation rich in arginine (peanuts, equivalent to 1 g of arginine/day) or with a low arginine content (wheat crackers, locally called daboqolo) during four weeks. The primary outcome was cure rate according to the WHO classification and secondary outcomes were sputum smear conversion, weight gain, sedimentation rate, reduction of cough and chest X-ray improvement as well as levels of NO in urine (uNO) or exhaled air (eNO) at two months. There was no effect of the intervention on the primary outcome (OR 1.44, 95% CI: 0.69-3.0, p = 0.39) or secondary outcomes. In the subgroup analysis according to HIV status, peanut supplemented HIV+/TB patients showed increased cure rate (83.8% (31/37) vs 53.1% (17/32), p < 0.01). A low baseline eNO (<10 ppb) in HIV+/TB patients was associated with a decreased cure rate. We conclude that nutritional supplementation with a food supplement rich in arginine did not have any overall clinical effect. In the subgroup of HIV positive TB patients, it significantly increased the cure rate and as an additional finding in this subgroup, low initial levels of NO in exhaled air were associated with a poor clinical outcome but this needs to be confirmed in further studies.
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Urinary nitric oxide excretion in infants with eczema.
Devenney, I, Norrman, G, Forslund, T, Fälth-Magnusson, K, Sundqvist, T
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2010;(1 Pt 2):e229-34
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Abstract
Eczema is characterized by inflammation of the skin and is commonly associated with food allergy. It has been suggested that nitric oxide (NO) is an important player in eczema, food allergy and intestinal inflammation. The aim of this study was to assess the levels of urinary NO breakdown products in infants with eczema and the effect of eczema treatment on NO levels. Ninety-four infants with eczema, 58 boys and 36 girls, with a mean age of 7.5 ± 5.2 months (mean ± s.d.) at inclusion were examined twice with an interval of 6 wk. The sum of nitrite and nitrate was measured colorimetrically in urinary samples from both visits and compared with clinical data concerning eczema severity, nutrition, gastrointestinal symptoms, asthma and skin prick positivity. The levels of NO products increased significantly from the first to the second visit: 289; 374 μm (median; IQR) vs. 457; 678 μm (median; IQR) (p < 0.001) in parallel with a significant improvement of the eczema. After eczema treatment consisting of skin care and elimination diet during the 6-wk interval between evaluations, the NO levels approached the values previously found in healthy children. The results support previous studies indicating that the homeostasis of nitrogen radicals is disturbed in childhood eczema.
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Urinary nitric oxide during one year of gluten-free diet with or without oats in children with coeliac disease.
Hollén, E, Forslund, T, Högberg, L, Laurin, P, Stenhammar, L, Fälth-Magnusson, K, Magnusson, KE, Sundqvist, T
Scandinavian journal of gastroenterology. 2006;(11):1272-8
Abstract
OBJECTIVE Although in both adults and children with coeliac disease (CD) it is now recommended that oats be added to their gluten-free diet, there is still some controversy concerning the possible harmful effects of oats in some individuals. In this study concentrations of nitric oxide metabolites were repeatedly measured in the urine of children under investigation for CD, when on a gluten-free diet with or without oats. MATERIAL AND METHODS The study included 116 children, randomized to a standard gluten-free diet (GFD-std) or a gluten-free diet supplemented with wheat-free oat products (GFD-oats), over a one-year period. Small-bowel biopsy was performed at the beginning and end of the study. Morning urine samples were collected from 87 children and urinary nitrite/nitrate concentrations were monitored at 0, 3, 6, 9 and 12 months. RESULTS All patients were in clinical remission after the study period. There was a rapid decline in urinary nitrite/nitrate concentrations in both groups as early as after 3 months. No differences were seen between the study groups at any of the checkpoints. However, at the end of the study, the nitrite/nitrate values of 9 children in the GFD-oats group and 8 children in the GFD-std group had not normalized. CONCLUSIONS Children with CD on a gluten-free diet with oats display a similar reduction in urinary nitrite/nitrate as those on a traditional gluten-free diet. Some children, however, still demonstrate high nitrite/nitrate excretion after one year on either diet, indicating that long-term follow-up studies of children on an oats-containing diet are needed.
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Coeliac children on a gluten-free diet with or without oats display equal anti-avenin antibody titres.
Hollén, E, Holmgren Peterson, K, Sundqvist, T, Grodzinsky, E, Högberg, L, Laurin, P, Stenhammar, L, Fälth-Magnusson, K, Magnusson, KE
Scandinavian journal of gastroenterology. 2006;(1):42-7
Abstract
OBJECTIVE Recent studies report negligible toxicity of oats in the majority of coeliac disease (CD) patients. It has previously been shown that children with untreated CD have circulating antibodies to oats avenin. In this study we performed serial assessments of anti-avenin antibodies in children under investigation for CD on a gluten-free diet with or without oats. MATERIAL AND METHODS The study involved 116 children, randomized to a standard gluten-free diet or a gluten-free diet supplemented with oats. Sera were obtained from 86 children, 48 in the standard gluten-free group and 38 in the gluten-free oats group, of which 33 consumed at least 10 g of oats daily. IgA and IgG anti-avenin antibodies were monitored at 0, 3, 6 and 12 months. Nitric oxide metabolites were measured in 7 patients, with deviating antibody results. RESULTS There was a significant decrease in anti-avenin antibodies in both groups at the end as compared to the beginning of the study, (p<0.001), but no difference was found between the two groups. IgA titres already declined after 3 months. IgG titres, although significantly decreased, remained high in the majority of patients in both groups. Nitric oxide levels were high in four of the analysed samples. CONCLUSIONS Oats per se, do not seem to produce a humoral immune reaction in children with CD when given in an otherwise gluten-free diet, indicating that the reaction requires gluten challenge. Anti-avenin antibodies were equal in the two study groups, and these findings strengthen the clinical impression that oats can be tolerated by the majority of patients with CD.
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Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis.
Schön, T, Elias, D, Moges, F, Melese, E, Tessema, T, Stendahl, O, Britton, S, Sundqvist, T
The European respiratory journal. 2003;(3):483-8
Abstract
Nitric oxide (NO) is involved in the host defence against tuberculosis (TB). Patients with TB exhibit increased catabolism and reduced energy intake. Thus the hypothesis for this study was that restoring a relative deficiency in the amino acid arginine, the substrate for mycobactericidal NO production, would improve the clinical outcome of TB by increasing NO production. In a randomised double-blind study, patients with smear-positive TB (n = 120) were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. Primary outcomes were sputum conversion, weight gain, and clinical symptoms after week 8. Secondary outcomes were sedimentation rate and levels of NO metabolites, arginine, citrulline, and tumour necrosis factor-a. Compared with the human immunodeficiency virus (HIV)-/TB+ placebo group, the HIV-/TB+ patients in the arginine group showed significant improvement, defined as increased weight gain, higher sputum conversion rate and faster reduction of symptoms, such as cough. The arginine level increased after week 2 in the HIV-/TB+ arginine group (100.2 microM (range 90.5-109.9) versus 142.1 microM (range 114.1-170.1)) compared with the HIV-/TB+ placebo group (105.5 microM (range 93.7-117.3) versus 95.7 microM (range 82.4-108.9)). HIV seroprevalence was 52.5%. No clinical improvement or increase in serum arginine was detected in arginine supplemented HIV+/TB+ patients compared with placebo. Arginine is beneficial as an adjuvant treatment in human immunodeficiency virus-negative patients with active tuberculosis, most likely mediated by increased production of nitric oxide.