Haptoglobin (Hp) alfa-chain alleles 1 and 2 account for three phenotypes (Hp1-1, 2-1 and 2-2) which have biologically important differences in their antioxidant, scavenging and immunomodulatory properties, and may thereby influence the course of inflammatory diseases. We investigated the haptoglobin polymorphism in patients with celiac disease and its possible association to the presenting symptoms. Methods: Seven-hundred-and-twelve unrelated, biopsy-proven Hungarian celiac patients (357 children, 355 adults); severe malabsorption: 32.9%, minor gastrointestinal symptoms: 22.8%, iron deficiency anemia: 9.4%, dermatitis herpetiformis: 15.6%, silent disease: 7.2%, others: 12.1%) and 384 healthy subjects were investigated. Haptoglobin phenotypes were determined by gel electrophoresis and assigned to corresponding genotypes.
Results: Hp2-1 was associated with an increased risk for celiac disease (p=0.0006, OR: 1.54, 95% CI: 1.20–1.98; prevalence: 56.9% in patients versus 46.1% in the control population). It was also overrepresented among patients with mild symptoms (69.2%) or silent disease (72.5%). The occurrence of Hp2-2 was lower than in controls (p=0.0023), but patients having this phenotype presented more often with severe malabsorption (OR: 2.21, 95% CI: 1.60–3.07), and accounted for 45.3% of all malabsorption cases. Haptoglobin phenotypes were similarly distributed among celiac and dermatitis herpetiformis patients. Conclusions: Haptoglobin polymorphism is associated with susceptibility to celiac disease and its clinical presentations. The predominant genotype in the investigated population was Hp2-1, while Hp2- 2 predisposed to a more severe clinical course. Phenotypedependent effect of haptoglobin may result from the molecule’s structural and functional differences.

Duodenal biopsy is an important tool to diagnose celiac disease, however, the most reliable location of biopsy site is still questionable. Claudins (CLDN), members of a large family of adherent junction proteins showing characteristic expression pattern in patients with cancer or inflammatory disorders, nevertheless, CLDN expression in celiac disease is unknown. Aim: Comparative study to examine the CLDN 2, 3 and 4 expressions in proximal and distal part of duodenum in children with celiac disease and in controls. Patients and methods: 33 children (range: 2-17 years, mean age: 6,4, 20 girls, 13 boys) with newly diagnosed celiac disease were enrolled. 14 healthy children (11 girls, 3 boys) served as controls. Biopsies from proximal (duodenal bulb) and distal part (duodenojejunal junction) of duodenum were taken for routine histological analysis. Severity of mucosal atrophy were determined by means of Marsh-scoring system. Immunohistochemistry were used to detect CD3+ intraepithelial lymphocytes and CLDN 2, 3 and 4 protein expressions. Results: Macroscopic picture (endoscopy), routine histology and Marsh grade depicted no differences between biopsies taken from proximal or distal part of duodenum. The densities of CD3+ intraepithelial T lymphocytes were significantly higher in proximal duodenum (p=0,026) and in distal duodenum in comparison to controls (p=0,006). CLDN 2 expression was significantly increased in severe form of celiac disease in bulb and in distal duodenum (p=0,001), and in distal part of non-severe celiac patients (p=0,02), in comparison to controls. CLDN 2 expression was significantly increased in severe form in proximal and in distal part also (p=0,04 and p=0,03) when compared with non-severe form. Similar association was found concerning CLDN 3 expression (bulb, p=0,008, distal, p=0,004). Moreover, CLDN 3 expression was markedly increased in proximal and in distal part of duodenum in severe form in comparison to controls. Expression of CLDN 4 was similar in all groups studied.
Conclusions: Both proximal and distal mucosal duodenal biopsies are suitable for diagnosing villous atrophy in patients with celiac disease, however, using more sensitive methods, the distal part of duodenum depicted earlier signs of mucosal deterioration. Therefore, to diagnose slight changes of mucosal abnormality the distal duodenum seems to be better location for intestinal biopsies. Increased expressions of CLDN 2 and 3 suggest structural changes of tight-junction in celiac disease which may be, at least in part, responsible for increased permeability and proliferation observed in celiac disease.

Genetic factors in oxidative process have been implicated in the pathogenesis of different liver diseases such as primary sclerosing cholangitis (PSC). Genetic factors seem to play a significant role in PSC also. Haptoglobin (Hp) is a haembinding glycoprotein with important antioxidant, scavenger and immunomodulant activity. Three major Hp phenotypes are known: 1-1, 2-1 and 2-2 which are different in structure and function. Antioxidant activity is more related to Hp type 1-1 than in type 2-2. In this study we investigated Hp polymorphism in pediatric and adult patients with PSC. Patients and methods: Hp phenotypes were determined by sodium dodecyl sulfate-polyacrylamid gel electrophoresis followed by immunoblotting in the sera of 39 patients (12 children, male 9, 27 adults, male 20) in comparison with 384 healthy controls. Results: In contrast to controls, none of the PSC patients showed Hp1-1 phenotype (Hp1-1 0% vs. 11.5%, ORHp1-1 vs. egyéb: 0.08, 95% CI: 0.005-1.32; p=0,008), however, the frequency of the other two fenotypes were similar to controls. Distribution of Hp phenotypes 2-1 and 2-2 were similar in children with PSC and in adults with PSC. Moreover, there was no difference of Hp distribution between PSC patients with or without chronic inflammatory bowel disease. Conclusion: Based on our result, PSC is the first disease, where there is no Hp1-1 genotype. Our findings suggest that Hp polymorphism through influencing the oxidative- and immunological processes may have a role in the pathomechanism of PSC.

On behalf of the of Hungarian Pediatric Gastroenterology Society prospective registry of pediatric inflammatory bowel disease (IBD) was launched from the 1st of January 2007 with the cooperation of 27 institutes (clinics, hospitals, outpatient departments) ensuring the coverage of the whole country. The survey data has been forwarded online to the center of the European Pediatric IBD Registry (Rotterdam). In recent epidemiological studies from Europe and North America the reported incidence of childhood Crohn disease (CD) is 3-4 cases per 100.000 per year, and of ulcerative colitis (UC) 2-3 cases per 100.000 per year. So far the incidence of IBD in Hungary is unknown. Methods: The participating institutes are requested to fill out a questionnaire (78 parameters) about every newly diagnosed IBD patients younger than 18 years. The questionnaire is about epidemiological and antropometrical data, main symptoms, diagnostic procedures (endoscopy, CT, MRI), and the detailed results of histological and imaging procedures. Results: During the first year of HUPIR 131 newly diagnosed cases of IBD were prospectively identified: 78 cases of CD, 44 cases of UC and 9 cases of indeterminate colitis. As a result the annual incidence of childhood IBD was 6,55 cases per 100.000 in 2007, with the incidence of CD being 3,8 cases per 100.000 per year, the incidence of UC 2,2 cases per 100.000 per year and the incidence of indeterminate colitis 0,45 cases per 100.000 per year. The mean age at diagnosis for all the 131 cases was 13,05 (range: 1,5–18 year), nevertheless, 3% of patients (4/131) were younger than 5 years. There was a male preponderance in CD, in contrast, sex ratio in UC patients were equal. Positive family history of IBD was registered in 8,4% of patients and 9% of patients with CD were reported to have a fistula. Ileoscopy rate was only 48%, technical problem was the most common reason for the lack of ileal intubation. Oesophagogastroduodenoscopy was performed in 50% of all cases. In 35% were MRI or CT scan made for the detailed verification of the disease. Conclusions: The incidences reported in the first year of HUPIR are similar to the European and North American data. The dominance of CD proved to be also consistent with other studies. Almost 10% of the patients with CD had fistula. Ileal intubation and oesophagoduodenoscopy were performed in the half of the cases, and this rate should be improved in the future.

Eosinophilic esophagitis (EE) is a recently recognized disorder characterized by the accumulation and infiltration of eosinophils in the mucosa of the esophagus. Symptoms of EE frequently mimic those of gastroesophageal reflux disease, but the two diseases are distinct in terms of clinics, histopathology and response to therapy. The EE involves the interplay of numerous genes, especially the eosinophil chemoattractant eotaxin-3, allowing distinction from other form of esophagitis and targeted therapeutic interventions. Our case report is presenting a successful diagnostic and therapeutic process of a girl suffering from EE.

Hematochezia in infancy has been explained mainly by allergic-/eosinophilic colitis (AC, EC) since usually these patients are otherwise asymptomatic and exhibited normal growth and physical examinations with normal fecal culture and no signs for fissure.
Aim: The objectives of this study were to evaluate prospectively the clinical course in breast-fed infants of rectal bleeding and evaluate basic laboratory findings, macroscopic and microscopic abnormality found in colonoscopy.
Patients: This study prospectively evaluated 44 consecutive breast-fed infants (age, 5.5 months, range, 25 days-11 months) who presented with fresh blood mixed with stools. None had evidence of a bleeding diathesis, bacterial enteritis or fissures. Elimination diet (cow’s milk, eggs, soya, nuts) was offered to the mothers for average 6 weeks. Colonoscopy was performed in 12 infants (mean age, 4.3 months, range, 25 days-7 months) due to severe or long-lasting hematochezia.
Results: Seven out of 12 patients had AC and 4/12 had eosinophilic colitis. Mean eosinophil density in AC was 14 (AC was diagnosed by means of eosinophils ł6 cells per high-power field: HPF), and mean eosinophil density in EC was 34 (EC was characterized histologically by ł20 eosinophils per HPF). Control biopsies showed only 1.48±0.78 eosinophils per HPF. There was a significant thrombocytosis (p<0.01) in AC patients (520±43×109/l) and elevated in EC patients (499±45×109/l) in comparison to controls (328±16×109/l). However, blood eosinophils were not elevated in AC nor in EC patients (AC, 3.66±0.78, EC, 3.25±1.25, controls, 4.95±1.87%). Colonoscopy revealed lymphonodular hyperplasia more often in AC (87.5%) than in EC (50%), in contrary, aphthous ulcerations were more common in EC (75%) than in AC (50%), nevertheless, the discrepancies failed to reach significance.
Summary: AC and EC are very common in otherwise asymptomatic breast-fed infants with normal fecal culture or without other obvious diseases after long-lasting hematochezia. AC and EC patients showed thrombocytosis with normal blood eosinophils. There was no difference between AC and EC concerning laboratory data, however, lymphonodular hyperplasia was more often in AC, and aphthous ulcerations were more common in EC patients at colonoscopy.

To investigate the relationship between trans fatty acids and long chain polyunsaturated fatty acids during lactation. Persons and methods: We investigated human milk samples of lactating mothers (n=769) participating in a German birth cohort study. Fatty acid composition of human milk samples was determined by high resolution gas-liquid chromatography. Results: We found significant positive correlations between values of trans hexadecenoic acid (C16:1n-7t) and values of arachidonic acid as well as values of n-6 long chain polyunsaturated fatty acids. In contrast, we found significant negative correlations between the 18-carbon trans octadecenoic acid (C18:1n-7/9t) and the values of the n-6 essential fatty acid, linoleic acid, its metabolite, arachidonic acid, the n-3 essential fatty acid, alpha-linolenic acid and its metabolite, docosahexaenoic acid. We also found significant and inverse correlation between, on the one hand, trans octadecadienoic acid (C18:2n-6tt) and the sum of trans fatty acids and, on the other hand, the values of all the investigated n-3 and n-6 fatty acids. Conclusion: Similarly to our previous studies investigating blood samples of expecting women and newborns, in our present study we also found significant negative correlations between the 18- carbon trans fatty acids and the long chain polyunsaturated fatty acid metabolites. Our results suggest that trans fatty acids originating from the maternal diet may disturb the availability of essential fatty acids and their long chain polyunsaturated metabolites in the human milk.

The aim of this review was to systematically summarise available data on n-3 and n-6 polyunsaturated fatty acid composition of plasma and erythrocyte membrane lipids in expecting women during the pregnancy and at delivery. We performed electronic literature search in English (Pubmed, Embase, Google Scholar) and in German (Springerlink) databases. We found 113 potentially relevant articles, from them 20 fit the inclusion criteria. Most of the authors investigated fatty acid composition of total plasma, total erythrocyte membrane lipids and plasma phospholipids. We were able to classify data collection into three time points: the second and third trimester at pregnancy, and delivery. We calculated the mean and the 95% confidence intervals for each n-3 and n-6 fatty acid at each investigated time point. Both n-3 and n-6 fatty acids were found in a narrower range in plasma phospholipids than in total plasmalipids. Ranges of linoleic acid, arachidonic acid, alphalinolenic acid and docosahexaenoic acid did not change remarkably during pregnancy. We calculate that in supplementational studies on pregnant women changes in the plasma phospholipids fraction may better reflect the fatty acid supply, than changes of fatty acid concentration of erythrocyte membrane lipids or total plasma lipids. Mean (95% confidence interval) data for plasma phospholipid arachidonic acid and docosahexaenoic acid values obtained in this systematic literature search may be used as reference values in studies supplementing expecting women with long-chain polyunsaturated fatty acids.

Recent literature of therapy of inflammatory bowel diseases (IBD) is reviewed. Difficulties are caused in the treatment of children by the facts that there are only a few controlled therapeutic data in connection of pediatric IBD and generally accepted treatment protocols are missing. The therapeutic possibilities has expanded significantly in the recent years. Although there are no opportunities for causal therapy so far, several adult and pediatric studies show that top down therapy (early intervention with immunmodulators and biological agents inducing mucosal healing) could favorably alter the natural course of IBD: prolonged remission can be achieved, the hospitalization and surgery decrease and the quality of life improves. Early markers exactly predicting the later course of disease are not known until now. Prospective clinical studies are needed to show how the patients requiring top down therapy should be selected, what is the risk-benefit ratio and whether the turn of therapeutic pyramid will fulfill expectations.

Infantile colic and functional constipation belong to the functional gastrointestinal disorders of infants. Clinical symptoms of these syndromes can be alleviated by the modulation of the lactose content in the infant’s formulae. In infantile colic the decrease, while in functional constipation the increase of lactose intake may be effective. According to our observations the Novolac IT with increased lactose concentration in 80 percents and the Novolac AC with decreased lactose content in 70 percents of studied cases were able to improve the clinical symptoms in functional constipation and infantile colic, respectively.