Cytokine tumor necrosis factor-alpha A promoter gene polymorphism at position -308 G-->A and pediatric inflammatory bowel disease: implications in ulcerative colitis and Crohn's disease.

OBJECTIVES: Our pilot study aimed to determine the effect of tumor necrosis factor-alpha (TNF-alpha) 308 G-->A promoter single-nucleotide polymorphism in pediatric inflammatory bowel disease (IBD), its influence on inflammatory activity and the clinical manifestations. METHODS: We obtained genomic DNA from 164 subjects, 82 with long-standing IBD aged 8 to 18 years: 46 with Crohn disease (CD) and 36 with ulcerative colitis (UC). Eighty-two healthy children served as the control population. Genotyping was determined by using a restriction enzyme-based assay. TNF-alpha 308 G-->A polymorphism was assessed in terms of inflammatory (C-reactive protein [CRP]) and disease activity. The latter was assessed by the Pediatric Crohn's Disease Activity Index (PCDAI) and the Truelove index for CD and UC, respectively. RESULTS: Significant differences in TNF-alpha 308 A polymorphism were found between the IBD group and controls (P < 0.05) and the UC group and controls (P < 0.001). No differences were noted between TNF-alpha 308 A polymorphism and clinical characteristics in UC. The frequency of the -308 A allele of TNF was not different in CD compared with that in the control group. The frequency of TNF-alpha 308 A genotype was significantly higher in CD patients with predominantly stenosing/penetrating disease compared with patients without complications (P < 0.001) and healthy controls (P < 0.01). In CD patients, those carrying TNF -308 A had a significant increase in CRP (P < 0.05) and the PCDAI (P < 0.05). In CD, CRP levels strongly correlated with the PCDAI (r = 0.6150, P < 0.001). In UC, significant differences among the mean levels of CRP (P < 0.05) and disease activity (P < 0.001) related to TNF-alpha 308 A polymorphism were found. Allele distribution (odds ratio, 12.9; CI, 1.18-140.81, P < 0.001) and CRP serum levels (odds ratio, 1.020; CI, 1.00-1.04, P < 0.001) were independently associated with CD complications. CONCLUSIONS: Although not necessarily dictating IBD initiation, the TNF-alpha 308 A polymorphism may play a role in modifying the CD phenotype. The polymorphism may influence disease activity as well as more intense inflammatory activity in both forms of IBD and may modify the progression of chronic digestive tract inflammation.

Effects of a specially designed fermented milk product containing probiotic Lactobacillus casei DN-114 001 and the eradication of H. pylori in children: a prospective randomized double-blind study.

GOALS: To determine the efficacy of triple therapy supplemented with a specially designed fermented milk product containing specific probiotic Lactobacillus casei (L. casei) DN-114 001 strain on Helicobacter pylori eradication in children. BACKGROUND: Lactobacillus species possess in vitro activity against H. pylori. There are no consistent data on the impact of eradication therapy supplemented with probiotics on H. pylori cure rates in childhood in vivo. STUDY: Multicenter, prospective, randomized, double-blind controlled study. Eighty-six symptomatic H. pylori-positive children were randomized either to receive the control treatment of omeprazole, amoxicillin, and clarithromycin (OAC) for 7 days or the test treatment of omeprazole, amoxicillin, and clarithromycin for 7 days supplemented with fermented milk (Actimel) containing L. casei DN-114 001 (OAC-LC), for 14 days. H. pylori status was assessed at 4 weeks following therapy using two noninvasive tests. RESULTS: Intention-to-treat (ITT) based eradication rates for the OAC-LC group were 84.6% (95% CI, 71.2%-95.5%), and 91.6% (95% CI, 76.9%-98.2%) by per-protocol (PP) analysis. Eradication in the OAC group was 57.5% (95% CI, 42.2%-72.3%) in the ITT set and 61.3% (95% CI, 44.4%-75.0%) in the PP group. Eradication success was higher in the OAC-LC group compared with the OAC group in both ITT (P=0.0045) and PP analysis (P=0.0019). Primary resistance for clarithromycin could be determined in 21.2%. Side effects were infrequent. Drug compliance was good throughout the study. CONCLUSION: Supplementation with fermented milk, containing live special probiotic L. casei DN-114 001, confers an enhanced therapeutic benefit on H. pylori eradication in children with gastritis on triple therapy.

Aspects of oxidative stress in children with type 1 diabetes mellitus.

Diabetes mellitus is considered to be one of a rank of free radical diseases. The existence of hyperglycemia produces increased oxidative stress (OS) via non-enzymatic glycation, glucose autoxidation, and alterations in polyol pathway activity with subsequent influences on the whole organism. In childhood, Type 1 diabetes prevails and is characterized by its autoimmune character with progressive destruction of beta cells and lack of insulin in genetically predisposed patients. Our study focused on diabetic children and their 1st degree relatives and confirmed increased oxidative stress in diabetic children as well as a similar tendency in their siblings. Following this, we carried out a one-year study comprising diabetic children supplemented with vitamins E and C. The vitamin treatment improved diabetes control and reduced markers of oxidative stress substantially when compared with non-supplemented diabetic children. As oxidative stress impairs not only lipids and proteins, but also DNA, we attempted to examine the level of DNA strand breaks as well as DNA repair processes using comet assay modifications. Though children with Type 1 diabetes demonstrated increased oxidative stress (lower SOD and GSH when compared with healthy children), their oxidative DNA damage (measured as DNA strand breaks) were not substantially altered compared with normals. On the other hand, their DNA repair capacity was significantly increased. This demonstrates a stimulated DNA repair process that is most certainly a response to the permanently elevated state of oxidative stress. Owing to the presented results, it is appropriate to ponder the increased influence of oxidative stress on children with Type 1 diabetes and to take into account this fact when considering their treatment.

Gastric emptying of solids in children with H. pylori-positive and H. pylori-negative non-ulcer dyspepsia.

OBJECTIVE: There is currently no data available in children on possible relationships among Helicobacter pylori, gastric motility and gastric inflammation. This is a prospective study of gastric emptying (GE) in symptomatic children with and without H. pylori who met symptom-based criteria for non-ulcer dyspepsia (NUD). METHODS: 47 consecutive dyspeptic patients (23 males; age range, 7 to 18 years) were enrolled. All patients had extensive negative diagnostic investigations. Scintigraphic solid-phase gastric emptying was assessed. RESULTS: 21 H. pylori-positive and 26 H. pylori-negative patients were identified with non-ulcer dyspepsia. The groups were not different in clinical symptoms except that pain related to feeding was more frequent in infected children (P < 0.03). Nodular antral gastritis was found more frequently in the H. pylori positive group (P < 0.0001). The gastritis score was more severe in H. pylori infected than H. pylori negative patients in both fundic and body mucosa (P < 0.001). Within the H. pylori-positive NUD group, the mean half-time GE of a solid meal was significantly accelerated compared to the non-infected group (P < 0.05). There was no difference in the intragastric food distribution and curves of gastric emptying of both groups. A significant relationship was found between the degree of gastric body inflammation gastric emptying, but not antral inflammation. Gastric emptying rate did not differ by sex or age of the subjects in either group. CONCLUSIONS: In dyspeptic children with H. pylori, gastric emptying of a solid was significantly accelerated compared with symptomatic H. pylori uninfected patients. This suggests that H. pylori is able to induce gastric emptying acceleration. Our findings add more information on H. pylori infection and gastroduodenal disease.

Acquired angioedema and Helicobacter pylori infection in a child.

UNLABELLED: We describe a 10-year-old boy with acquired Helicobacter pylori infection and simultaneous angioedema which is a rare but life-threatening condition. Our patient was hospitalised with generalised angioedema and severe circulatory shock due to extreme loss of fluids and proteins into interstitial tissues (weight gain 10 kg within 2 days, extreme haemoconcentration--haemoglobin 206 g/l, haematocrit 0.570, leucocytosis 18,300 /microl, high lactate 13.8 mmol/l) and simultaneous failure of the complement system (C3 <0.16 g/l, C4 <0.13 g/l, CH50 45 U/ml, i.e. 50% of normal value, C1 inhibitor 0.21 g/l at the lower limit). All possible known causes of angioedema were excluded (infection, allergy, auto-immune disease, NSAIDs, lymphoproliferative disease) except for the simultaneous H. pylori infection which was proven serologically and histologically. Eradication therapy led to a complete remission of the H. pylori infection. An absence of angioedema and the restoration of the complement system was later observed. To the best of our knowledge, no similar case report of a child has yet been published. CONCLUSION: Helicobacter pylori infection should be considered in the development of angioedema in childhood.

Parameters of oxidative stress in children with Type 1 diabetes mellitus and their relatives.

Oxidative stress (OS) plays an important role in the pathogenesis of Type 1 diabetes mellitus (DM). The aim of the study was to compare OS parameters in diabetic children and their first-degree relatives. Fifty diabetic children from the West Bohemian Region were examined as well as their 32 siblings (12 Boys and 20 girls) and 65 of their parents during a period of 6 months. Thirty healthy sex- and age-matched children studied before planned surgeries were normal controls for children, 40 healthy adult volunteers were controls for parents. OS parameters were evaluated in all participants of the study (superoxide dismutase, SOD; glutathione peroxidase, GSHPx; plasma antioxidant capacity, AOC; reduced glutathione, GSH; and malondialdehyde, MDA) and also Type 1 DM-associated antibodies (ICA and GADA). The results in diabetic children showed significantly lower GSHPx and AOC and increased MDA when compared with healthy children. Similar findings were found in their siblings but without statistical significance. It is consequently evident that decreased antioxidative protection and simultaneous free radical (FR) overproduction occur in diabetic children and that there is a similar, but not significant, tendency in their siblings. The findings warrant reducing OS in diabetic children and postponing disease onset in susceptible relatives.