Relationships between disaccharidase deficiencies, duodenal inflammation and symptom profile in children with abdominal pain.

Abdominal pain has been associated with disaccharidase deficiencies. While relationships with individual symptoms have been assessed, relationships between disaccharidase deficiencies and symptom complexes or inflammation have not been evaluated in this group. The primary aims of the current study were to assess relationships between disaccharidase deficiency and symptoms or symptom complexes and duodenal inflammation, respectively. Patients with abdominal pain who underwent endoscopy with evaluation of disaccharidase activity levels were identified. After excluding all patients with inflammatory bowel disease, celiac disease, H. pylori, or gross endoscopic lesions, patients were evaluated for disaccharidase deficiency frequency. Disaccharidase were compared between patients with and without histologic duodenitis. Lastly, relationships between individual gastrointestinal symptoms or symptom complexes were evaluated. Lactase deficiency was found in 34.3% of patients and disaccharidase pan-deficiency in 7.6%. No individual symptoms or symptom complexes predicted disaccharidase deficiency. While duodenitis was not associated with disaccharidase deficiency, it was only present in 5.9% of patients. Disaccharidase deficiency, particularly lactase deficiency, is common in youth with abdominal pain and multiple deficiencies are not uncommon. Disaccharidase deficiency cannot be predicted by symptoms in this population. Further studies are needed to assess the clinical significance of disaccharidase deficiency.

Distribution of duodenal tuft cells is altered in pediatric patients with acute and chronic enteropathy.

Clinical interest into the function of tuft cells in human intestine has increased in recent years. However, no quantitative study has examined intestinal tuft cells in pathological specimens from patients. This study quantified tuft cell density by using a recently identified marker, specific for tyrosine phosphorylation (pY1798) of girdin (also known as CCDC88A or GIV) in the duodenum of pediatric patients. Deidentified sections with pathological diagnosis of acute duodenitis, ulcer, or celiac disease, and age-matched normal control were analyzed under double-blind conditions. Immunostaining for pY1798-girdin demonstrated the distinct shape of tuft cells with and filopodia-like basolateral membrane structure and a small apical area, which densely expressed gamma-actin. As compared to normal tissues, the specimens diagnosed as celiac disease and duodenal ulcer had significantly fewer tuft cell numbers. In contrast, acute duodenitis showed varied population of tuft cells. The mucosa with severe inflammation showed lower tuft cell numbers than the specimens with none to mild inflammation. These results suggest that loss of tuft cells may be involved in prolonged inflammation in the duodenal mucosa and disrupted mucosal integrity. pY1798-girdin and gamma-actin are useful markers for investigating the distribution and morphologies of human intestinal tuft cells under healthy and pathological conditions.

Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine.

BACKGROUND AND AIMS: Nucleotide oligomerization domain 2 [NOD2] mutations are key risk factors for Crohn's disease [CD]. NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the exact roles of NOD2 in CD and other NOD2-associated disorders remain poorly known. METHODS: We initially observed that NOD2 expression was increased in epithelial cells away from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation, and cytokines expression were examined in the small bowel of wild-type [WT], Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulphonic acid [TNBS]. RESULTS: In WT mice, Nod2 upregulation upstream to rectal injury was associated with pro-inflammatory cytokine expression but no overt histological inflammatory lesions. Conversely, in Nod2-deficient mice the inflammation spread from colitis to ileum and duodenum. CONCLUSIONS: Nod2 protects the gut from colitis spreading to small intestine.

Taurine regulates mucosal barrier function to alleviate lipopolysaccharide-induced duodenal inflammation in chicken.

The objective of the study was to investigate how taurine alleviates mucosal injury. Young chickens were fed with taurine for 1 week and then challenged with lipopolysaccharide. We found that, under lipopolysaccharide challenge, taurine could attenuate diarrhea and mucosal inflammation. Additionally, under LPS challenge, taurine could enhance epithelial proliferation and goblet cell function, could also decrease epithelial apoptosis by improving the mitochondrial membrane permeability. The high-performance liquid chromatography assay showed that taurine feeding could elevate taurine concentration in duodenum obviously. The antioxidant assay showed that taurine could reverse lipopolysaccharide-induced low GSH level, GSH/GSSG ratio, GSH-Px activity and SOD activity, high GSSG and MDA content. In summary, we suggested that taurine could enhance duodenal antioxidant status locally and further ameliorated lipopolysaccharide-induced chicken duodenal inflammation by improving mitochondrial membrane permeability and goblet cell function.

Duodenal mucosa FOXP3 expression in different etiologies of lymphocytic duodenosis.

BACKGROUND/AIMS: In celiac disease there is an increase of lymphocytes expressing FOXP3 in the intestinal mucosa associated with varying degrees of villous atrophy. Our aim was to evaluate FOXP3 expression in duodenal mucosa with lymphocytic enteritis according to aetiology and correlation with lymphocytes T-γδ. METHODS: We compared three adult patient groups suffering lymphocytic enteritis: celiacs following a gluten-free diet (n=12), first-degree relatives of celiac patients with genetic risks (n=14) and patients with functional dyspepsia (n=14), along with a control group not suffering from duodenal enteritis (n=16). The population of duodenal lymphocytes was analysed by immunohistochemistry assays for CD3+ characterisation and FOXP3 expression. Quantification of lymphocytes T-γδ in duodenal mucosa was performed by flow cytometry in fresh tissue samples. RESULTS: Presence of lymphocytes T-γδ was significantly higher in the group of celiac individuals compared to the group of relatives of these individuals (37.44 vs 5,52: p<0.0001) and the group with functional dyspepsia (37.44 vs 11.76: p=0.008). FOXP3 expression was also significantly higher in the celiac group than in the groups of relatives (18.85 vs 6.31; p=0.001) and functional dyspepsia patients (18.85 vs 7.61; p=0.023). The proportion of lymphocytes T-γδ and FOXP3- expressing lymphocytes was similar in the control group to that in the relatives or functional dyspepsia groups. CONCLUSIONS: Lymphocytic enteritis associated to celiac disease shows an increase of FOXP3 expression and lymphocytes T-γδ that is not detected in other etiologies of enteritis.

Childhood chronic gastritis and duodenitis: Role of altered sensory neuromediators.

AIM: To investigate the roles of the neuropeptides vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) in chronic gastritis and duodenitis in children. METHODS: Biopsy samples from the gastric and duodenal mucosa of 52 patients and 30 control subjects were obtained. Samples were taken for pathological examination, immunohistochemical staining, enzyme activity measurements and quantitative measurements of tissue peptide levels. RESULTS: We observed differential effects of the disease on peptide levels, which were somewhat different from previously reported changes in chronic gastritis in adults. Specifically, SP was increased and CGRP and VIP were decreased in patients with gastritis. The changes were more prominent at sites where gastritis was severe, but significant changes were also observed in neighboring areas where gastritis was less severe. Furthermore, the degree of changes was correlated with the pathological grade of the disease. The expression of CD10, the enzyme primarily involved in SP hydrolysis, was also decreased in patients with duodenitis. CONCLUSION: Based on these findings, we propose that decreased levels of VIP and CGRP and increased levels of SP contribute to pathological changes in gastric mucosa. Hence, new treatments targeting these molecules may have therapeutic and preventive effects.

Loss of intestinal O-glycans promotes spontaneous duodenal tumors.

Mucin-type O-glycans, primarily core 1- and core 3-derived O-glycans, are the major mucus barrier components throughout the gastrointestinal tract. Previous reports identified the biological role of O-glycans in the stomach and colon. However, the biological function of O-glycans in the small intestine remains unknown. Using mice lacking intestinal core 1- and core 3-derived O-glycans [intestinal epithelial cell C1galt1(-/-);C3GnT(-/-) or double knockout (DKO)], we found that loss of O-glycans predisposes DKO mice to spontaneous duodenal tumorigenesis by ∼1 yr of age. Tumor incidence did not increase with age; however, tumors advanced in aggressiveness by 20 mo. O-glycan deficiency was associated with reduced luminal mucus in DKO mice before tumor development. Altered intestinal epithelial homeostasis with enhanced baseline crypt proliferation characterizes these phenotypes as assayed by Ki67 staining. In addition, fluorescence in situ hybridization analysis reveals a significantly lower bacterial burden in the duodenum compared with the large intestine. This phenotype is not reduced with antibiotic treatment, implying O-glycosylation defects, rather than bacterial-induced inflammation, which causes spontaneous duodenal tumorigenesis. Moreover, inflammatory responses in DKO duodenal mucosa are mild as assayed with histology, quantitative PCR for inflammation-associated cytokines, and immunostaining for immune cells. Importantly, inducible deletion of intestinal O-glycans in adult mice leads to analogous spontaneous duodenal tumors, although with higher incidence and heightened severity compared with mice with O-glycans constitutive deletion. In conclusion, these studies reveal O-glycans within the small intestine are critical determinants of duodenal cancer risk. Future studies will provide insights into the pathogenesis in the general population and those at risk for this rare but deadly cancer.

[CLINICAL FEATURES AND OPTIMIZATION OF THE TREATMENT OF CHILDREN WITH COMBINATION GASTRODUODENAL PATHOLOGY AND PRIMARY HYPERTENSION].

The paper present dynamic of clinical picture, daily blood pressure monitoring results and subjective assessment of functional status in children with combination of chronic gastroduodenal pathology and primary hypertension when L-carnitine used with the standard treatment regimen.

Collagenous gastroduodenitis with recurrent gastric ulcer in 12-year-old girl.

This report describes a rare case of collagenous gastroduodenitis found in a 12-year-old Japanese girl who had recurrent hematemesis. Gastrointestinal endoscopy showed many lotus leaf-like lesions on the gastric mucosa surrounded by atrophic gastric mucosa in the antrum, with a cobblestone appearance and a scarred duodenal ulcer in the duodenal bulb. A biopsy of the gastric mucosa indicated subepithelial collagen band. The patient was treated with H2-blockers for her symptoms for 4 years following the endoscopic findings. Follow-up endoscopy showed the same appearance as before. The pathology, however, showed a more prominent subepithelial collagen deposition. To make the correct diagnosis, it is critical to know from which part the pathological biopsy specimens were taken because there were numerous collagen bands in the atrophic membrane. It is important to monitor the patient regularly for evaluation of the etiology, pathogenesis and prognosis of this rare disease.

[Causes of chronic gastrodudenal and bone disorder development in children living under the effect of human induced ecological factors (literature review)].

The literature review discloses modern ideas about new etiological factors that that cause gastroduodenitis and bones metabolism dysfunctions in children. The authors cite literature data that give evidence to possible common mechanisms of development of these pathological conditions associated with exposure to man-made factors, such as heavy metals. Metals that have damaging effect on the epithelial cells of the gastrointestinal tract may violate calcium absorption processes in organism, influence on the processes of bone remodeling. At the same time, patterns of chronic gastroduodenitis associated with exposure to unhealthy environmental factors may increase the risk of osteopeny. Knowledge of new pathogenic mechanisms of chronic gastroduodenitis and bones metabolism dysfunctions will allow to provide effective treatment and prevention of comorbidities in children living in ecologically unsafe areas.

An examination of the relationship between the endoscopic appearance of duodenitis and the histological findings in patients with epigastric pain.

The endoscopic appearance of duodenitis is a common finding in patients undergoing endoscopy because of epigastric pain however, the relationship of the visual findings to histology is poorly defined. We set out to ascertain if there was a correlation between the endoscopic and histological appearances of the duodenal mucosa. Consecutive patients with epigastric pain referred for diagnostic gastroduodenoscopy were studied. The visual appearances of 'duodenitis' (erythema, erosions and sub-epithelial haemorrhage) were reported independently by two endoscopists. Duodenal biopsies were taken and assessed for: neutrophil infiltrate, mononuclear infiltrate, gastric metaplasia, villous atrophy and a breach in the mucosa. H pylori status was determined. Of the 93 patients with endoscopic features of duodenitis an increase in histological markers of inflammation was found in 75 (81%). However, histological inflammation was absent or minimal in 68 (73%). Conversely, biopsies from normal-looking mucosa revealed histological evidence of inflammation in 26 (27%). For patients with the endoscopic features of duodenitis the positive & negative predictive value for neutrophilic infiltrate was 39% and 98% respectively. Biopsies from erosions confirmed a breach in the mucosa in only 2 of 40 patients. Neutrophilic infiltrate occurred with NSAI ingestion and infection with H pylori. The endoscopic appearance of the duodenal mucosa is unreliable in determining the presence of histological inflammation. The endoscopic appearance of 'erosions' is not usually associated with a mucosal breach.

[The ingredients of the gastric and duodenum mucosa secretions in chronic gastroduodenitis in adolescents].

Number of children with chronic gastroduodenitis and duodenal ulcer, is increasing every year. A major role in the development of chronic inflammation of the mucous membrane of the gastroduodenal zone play cytoprotective properties of mucus produced blennogenic structures of these bodies. Therefore, the appointment of therapies to help improve the cytoprotective properties of gastric and duodenal ulcers, remains valid. Presents the results of the study lektingistohimicheskogo slizeobrazovaniya with chronic gastroduodenitis in adolescents.

Russell body duodenitis: a histopathological and molecular approach to a rare clinical entity.

Russell bodies are pink eosinophilic accumulations within plasma cells. To date, two hypotheses have attempted to elucidate the biological events behind the formation of these bodies. One theory sustains that such bodies constitute cytoplasmic accumulation of immunoglobulin derivatives contained in the perinuclear cistern of the smooth endoplasmic reticulum because of an increased synthesis or altered secretion. On the other hand, since its initial description in the medical literature, several authors have attributed the formation of such bodies to the presence of microorganisms such as in the case of Russell body gastritis and its association to Helicobacter pylori infection. In an attempt to possibly characterize the presence of an infectious organism, we performed a thorough biomolecular analysis on a case of a 69-year-old female presenting with Russell body duodenitis which, to the best of our knowledge, constitutes the second report of this clinical entity in the English literature. In light that the events behind formation of such bodies in H. pylori-negative individuals remain unclear, we hypothesize on the possible pathways that could have led to their reactive mechanical and immune derivation.

Effects of acute and chronic inflammation on proteins involved in duodenal iron absorption in mice: a time-course study.

In order to understand better the molecular mechanisms involved in the pathogenesis of anaemia of inflammation, we carried out a time-course study on the effects of turpentine-induced acute and chronic inflammation on duodenal proteins involved in Fe absorption in mice. Expression levels of these proteins and hepatic hepcidin and serum Fe levels were determined in inflamed mice. In acutely inflamed mice, significantly increased expression of ferritin was the earliest change observed, followed by decreased divalent metal transporter 1 expression in the duodenum and increased hepcidin expression in the liver. Ferroportin expression increased subsequently, despite high levels of hepcidin. Hypoferraemia, which developed at early time periods studied, was followed by increased serum Fe levels at later points. The present results thus show that acute inflammation induced several changes in the expression of proteins involved in duodenal Fe absorption, contributing to the development of hypoferraemia. Resolution of inflammation caused attenuation of many of these effects. Effects in chronically inflamed mice were less consistent. The present results also suggest that inflammation-induced increases in ferritin appeared to override the effects of hepcidin on the expression levels of ferroportin in enterocytes.

[Relationship of gastric microflora and neopterin content in gastric juice in children with chronic gastroduodenitis].

The study included 71 children with chronic gastroduodenitis aged 5-17 years. PCR DNA was determined by the presence of Helicobacter pylori, human papilloma virus high cancer risk 16, 18 types (HPV), herpes simplex 1 and type 2 (HSV), cytomegalovirus (CMV), fungi, Candida in gastric juice and biopsy specimens of gastric mucosa and duodenal. Viruses were detected in 14% of patients, an association of microorganisms - in 20% of the children, the isolated H. pylori infection - 18%. The relationship between the composition of microflora in the gastroduodenal region and neopterin levels in gastric juice with a distinct increase in its value in the presence of viruses.

[Clinical and morphological substantiation of SMC-peloidotherapy for the management of duodenal pathology].

This study included 112 patients presenting with duodenal ulcer disease and 65 ones with chronic duodenitis treated with the use of sinusoidal modulated current (SMC) electrophoresis in combination with peloidotherapy (peat muds of the Uva health resort, Republic of Udmurtia). This treatment was shown to produce positive effect on the proliferative activity of duodenal epithelium.

Lysozyme-rich mucus metaplasia in duodenal crypts supersedes Paneth cells in celiac disease.

Lysozyme is as an innate enzyme with potent antibacterial properties found in Paneth cells in normal duodenal crypts. Since celiac disease concurs with an abnormal duodenal microbiota we explored the expression of lysozyme in this disease. Fifty-three duodenal biopsies were stained with anti-lysozyme: 15 had normal duodenal mucosa (NDM), 7 chronic active duodenitis (CAD), 3 borderline (BL), 17 subtotal villous atrophy (SVA) and 11 total villous atrophy (TVA). NDM showed lysozyme-positive Paneth cells arranged in "Indian file" in 93.3%. In contrast, lysozyme-positive mucus metaplasia in crypts (LPMMC) replacing Paneth cells was found in 71.5% in CAD, in 96.4% in SVA/TVA, and in 2 cases with B. In 19.3% cases with BL/SVA/TVA, LPMMC replaced all Paneth cells in all crypts in entire sections. In crypts and villi, lysozyme-positive goblet cells (LPGC) were found in 92.8%. Changes were more frequent in the duodenal bulb than in pars descendens. In normal duodenal mucosa, absorptive enterocytes and goblet cells migrate from stem cells upwards, while Paneth cells migrate downwards, towards the base of the crypts. In celiac disease stem cells seem to have been re-programmed, as the normal production of Paneth cells in the crypts was replaced by lysozyme-producing mucus cells. LPMMC and LPGC in celiac disease might mirror an antimicrobial adaptation of stem cells to signals generated by pathogenic duodenal bacteria. The molecular mechanism(s) behind the abrogation of Paneth cells in duodenal crypts and its substitution by LPMMC in celiac disease remains to be elucidated.

[Morphological characteristics of duodenum mucosa in children with atopic dermatitis].

The results of investigation of 87 children suffering from chronic gastroduodenitis and atopic dermatitis are presented. All the child underwent fibrogastroduodenoscopy with duodenal mucosal biopsy and diagnostics of Helicobacter pylori infection, lambliasis. Hystomorphological and immunohystochemical studies of mucosal biopsy specimens for Epstein - Barr virus were carried out. The role of atopy and infection factors in genesis of chronic gastroduodenitis was evaluated.