Absence Of Mucosal Damage Research Articles

Diagnosis of Seronegative and Ultrashort Celiac Disease

Nowadays celiac disease (CD) in its conventional form, characterized by both positive serology and flat villi in the duodenum, is well known by gastroenterologists and general practitioners. The aim of the present review is to shed light on two neglected and not yet well defined celiac phenotypes, i.e. seronegative and ultrashort celiac disease. Seronegative celiac disease can be suspected in the presence of flat villi, positive HLA-DQ2 and/or -DQ8 and absence of CD antibodies. After having ruled out other seronegative enteropathies, the diagnosis can be confirmed by both clinical and histological improvement after 1-year of gluten-free diet. Ultrashort celiac disease is characterized by the finding of flat villi in the duodenal bulb in the absence of mucosal damage in the distal duodenum and with serological positivity. Data on the prevalence, clinical manifestations, histological lesions, genetic features and outcome of seronegative and ultrashort celiac disease are inconclusive due the few studies available and the small number of diagnosed patients. Some additional diagnostic tools have been developed recently, such as assessing of intestinal transglutaminase 2 (TG2) deposits, the flow-cytometry technique, micro-RNA detection or proteomic analysis and they seem to be useful in the identification of complex patients. Further co-operative studies are highly desirable to improve the knowledge of these two still obscure variants of celiac disease.

Lactobacilli Degrade Wheat Amylase Trypsin Inhibitors to Reduce Intestinal Dysfunction Induced by Immunogenic Wheat Proteins

Wheat-related disorders, a spectrum of conditions induced by the ingestion of gluten-containing cereals, have been increasing in prevalence. Patients with celiac disease have gluten-specific immune responses, but the contribution of non-gluten proteins to symptoms in patients with celiac disease or other wheat-related disorders is controversial. C57BL/6 (control), Myd88-/-, Ticam1-/-, and Il15-/- mice were placed on diets that lacked wheat or gluten, with or without wheat amylase trypsin inhibitors (ATIs), for 1 week. Small intestine tissues were collected and intestinal intraepithelial lymphocytes (IELs) were measured; we also investigated gut permeability and intestinal transit. Control mice fed ATIs for 1 week were gavaged daily with Lactobacillus strains that had high or low ATI-degrading capacity. Nonobese diabetic/DQ8 mice were sensitized to gluten and fed an ATI diet, a gluten-containing diet or a diet with ATIs and gluten for 2 weeks. Mice were also treated with Lactobacillus strains that had high or low ATI-degrading capacity. Intestinal tissues were collected and IELs, gene expression, gut permeability and intestinal microbiota profiles were measured. In intestinal tissues from control mice, ATIs induced an innate immune response by activation of Toll-like receptor 4 signaling to MD2 and CD14, and caused barrier dysfunction in the absence of mucosal damage. Administration of ATIs to gluten-sensitized mice expressing HLA-DQ8 increased intestinal inflammation in response to gluten in the diet. We found ATIs to be degraded by Lactobacillus, which reduced the inflammatory effects of ATIs. ATIs mediate wheat-induced intestinal dysfunction in wild-type mice and exacerbate inflammation to gluten in susceptible mice. Microbiome-modulating strategies, such as administration of bacteria with ATI-degrading capacity, may be effective in patients with wheat-sensitive disorders.

The Ulcerative Colitis Endoscopic Index of Severity is Useful to Predict Medium- to Long-Term Prognosis in Ulcerative Colitis Patients with Clinical Remission.

The ulcerative colitis endoscopic index of severity [UCEIS] is a validated scoring system. Nevertheless, few studies have investigated its usefulness in clinical settings. In this study, we aimed to predict the clinical prognosis of patients with ulcerative colitis [UC] in clinical remission using the UCEIS. A total of 285 UC patients who underwent a colonoscopy between April 2012 and March 2013 were enrolled. We reviewed clinical characteristics and endoscopic scores at the time of the colonoscopy and checked the clinical remission rate of the patients until September 2015. Clinical remission and recurrence were defined as a partial Mayo score of ≤1 and ≥3, respectively. UCEIS was strongly correlated with the Mayo endoscopic score [r=0.93], moderately correlated with clinical severity [r=0.64] and mildly correlated with C-reactive protein [r=0.34]. The recurrence rate increased gradually as it became more endoscopically severe [5.0% for UCEIS=0, 22.4% for UCEIS=1, 27.0% for UCEIS=2, 35.7% for UCEIS=3 and 75.0% for UCEIS=4-5] in patients with clinical remission. UCEIS and the concomitant use of thiopurine were independent factors predicting clinical recurrence. A multivariate analysis indicated that the absence of bleeding [p≤0.001] and the absence of mucosal damage [p<0.001] in a colonoscopy were independent factors for prolongation of clinical remission. The UCEIS is useful to predict the medium- to long-term outcomes of UC patients with clinical remission. The absence of bleeding or mucosal damage is important for maintaining clinical remission.

No correlation between indomethacin‐induced gastroduodenal damage and inhibition of gastric prostanoid synthesis

The effect of 1 week of treatment with indomethacin 150 mg/day on human gastric prostanoid synthesis was correlated with its effect on gastric and duodenal mucosa. Before and following 1 week of treatment, endoscopic appearance of the mucosa was evaluated and scored. Following 1 week of treatment with indomethacin, antral PGE2 and 6-keto-PGF1 alpha were significantly lower than in normal subjects, but similar in patients with significant or with no mucosal damage. Co-treatment with ranitidine 150 mg b.d. or with cimetidine 400 mg b.d. reduced the mean mucosal damage score but did not affect gastric prostanoid synthesis, which was similar irrespective of the presence or absence of mucosal damage. It is therefore suggested that there is no correlation between indomethacin-induced inhibition of gastric prostanoid synthesis and its induction of mucosal damage.

The role of H2-receptor antagonists in the prevention of NSAID-induced gastrointestinal damage.

Non-steroidal anti-inflammatory drugs (NSAIDs) induce gastric and duodenal damage in animals and humans. The possible protection afforded by cimetidine against acute and short-term NSAID-induced mucosal damage was evaluated in five studies. Cimetidine 200 mg once daily and 400 mg once daily was found to protect the gastric mucosa against damage induced by a single dose of aspirin 1300 mg; this protection was found to be independent of gastric acid secretion. Cimetidine 200 mg q.d.s. was found to protect the stomach and duodenum against damage induced by 14 days' treatment with aspirin 650 mg q.d.s. Duodenal and gastric damage induced during a 7-day treatment period with naproxen 500 mg b.d. was prevented by cimetidine 400 mg b.d.; this dose of cimetidine also provided significant duodenal protection against damage induced by 1 week of therapy with indomethacin 50 mg t.d.s. There is no correlation between upper gastrointestinal symptoms, or between mucosal prostanoids, and the presence or absence of mucosal damage. Cimetidine is therefore effective in the prevention of mucosal damage induced by short-term treatment with NSAIDs.

Immunological studies in cows' milk protein-sensitive enteropathy.

55 infants, aged between 1 and 13 months, who presented with persistent diarrhoea were placed on a diet free of cows9 milk protein. The clinical condition of the infants improved and 6-8 weeks later each was challenged with low-lactose cows9 milk. The following investigations were performed before and 24 hours after provocation: jejunal biopsy, serum and duodenal juice levels of complement C3 and C4, C3-activator, and immunoglobulins A, G, M, and D. Three groups were recognised on postchallenge clinical symptoms together with histological changes in the jejunal mucosa: group 1 (n=10 infants) with no clinical or mucosal abnormality, group 2 (n=18 infants) with mucosal abnormalities but lacking clinical symptoms, and group 3 (n=27 infants) with mucosal abnormalities and clinical symptoms; but in group 3 symptoms were delayed for over 24 hours in 7 infants, and in the remaining 20 infants symptoms appeared within 24 hours. After provocation the serum IgG levels were decreased in 3 infants in group 1, 12 in group 2, and 17 in group 3. The mean serum IgA and IgM levels were higher in group 1 compared with group 2 or 3; pre- and postchallenge mean serum immunoglobulin levels, complement, and complement activator levels were of equal magnitude in all three groups. A depletion of serum complement C3 level was observed in 4 (group 1), 4 (group 2), and 13 (group 3) infants 24 hours after provocation with cows9 milk; the fall in serum IgG was often associated with depletion of complement in serum. This suggests the involvement in some infants of IgG-mediated complement-consuming immune reactions in the development of the damage in the intestinal mucosa. After challenge, exudation of IgG and IgA occurred irrespective of the presence or absence of mucosal damage and was not always associated with the decrease in serum IgG concentration. Because of the variable conditions present in the intestinal lumen it is suggested that the level of immunoglobulins in duodenal juice is not a reliable measure of the local immune response. Levels of complement and immunoglobulin in serum or duodenal juice fail to provide help in the diagnosis of cows9 milk protein-sensitive enteropathy.