Circulating ghrelin levels in patients with inflammatory bowel disease.
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Biomedical subjects
Publications and source records attributed to M T Bardella.
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BACKGROUND: A non-negligible percentage of patients with non-alcoholic fatty liver disease, a leading cause of hepatic progressive disorder related to insulin resistance, have no metabolic risk factors, and abnormal intestinal permeability has been suggested to be involved in the pathogenesis of the liver damage. Coeliac disease, a curable disorder characterised by inflammatory mucosal damage, may show hepatic histological features similar to steatohepatitis. Conflicting data have been reported on the prevalence of coeliac disease in non-alcoholic steatohepatitis. AIM: To search for coeliac disease in a series of patients with non-alcoholic fatty liver disease by screening with anti-tissue transglutaminase and anti-endomysium antibodies. PATIENTS AND METHODS: Fifty-nine consecutive patients with hypertransaminasemia and non-alcoholic fatty liver disease, 38 (64%) with steatohepatitis. Anti-endomysium antibodies were assayed by indirect immunofluorescence, IgA anti-tissue transglutaminase by ELISA. Patients who tested positive underwent HLA DQ typing and endoscopy. RESULTS: Tissue transglutaminase antibodies were positive in six (10%) patients and anti-endomysium in two (3.4%); only two (3.4%), positive for both anti-endomysium positive and anti-transglutaminase, resulted to have coeliac disease based on histological findings. After 6 months of gluten-free diet, liver enzymes normalised. CONCLUSIONS: The prevalence of silent coeliac disease is 3.4% in patients with non-alcoholic fatty liver. The inclusion of anti-endomysium antibodies test in studying patients with non-alcoholic fatty liver and persistent biochemical abnormalities has to be taken into account, since positivity for tissue transglutaminase antibodies, in the absence of confirmatory anti-endomysium antibodies, is not sufficient to perform diagnostic endoscopy.
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BACKGROUND: A life-long gluten-free diet is the treatment of choice for dermatitis herpetiformis, which is considered to be coeliac disease of the skin. OBJECTIVES: To investigate the effects on long-term remission of dermatitis herpetiformis in patients who underwent a gluten challenge and subsequently reintroduced dietary gluten. PATIENTS AND METHODS: We studied 38 patients (14 male and 24 female) with biopsy-confirmed dermatitis herpetiformis. They had followed a gluten-free diet for a mean of 8 years, achieving clinical remission and intestinal normalization. The patients were asked to reintroduce gluten in their diet and agreed to undergo skin and intestinal biopsies during the follow-up. RESULTS: Of the 38 patients abandoning a gluten-free diet, 31 reported the onset of rash within an average of 2 months. Seven subjects (three males, mean age 15 years at challenge) experienced no clinical or histological relapses (median follow-up 12 years), and lost IgA immunoglobulin from the skin. The two series of patients differed in terms of age at diagnosis (mean age: 26.6 vs. 6 years), the use of dapsone (one of 31 vs. four of seven) and adherence to the gluten-free diet (strict compliance in 26 of 31 vs. none of seven). CONCLUSIONS: Our data suggest that the ingestion of small doses of gluten in childhood and/or the use of an anti-inflammatory drug may modify the immunological response inducing immune tolerance. We report long-term clinical and histological remissions in seven patients with dermatitis herpetiformis after the reintroduction of dietary gluten.
BACKGROUND: In an attempt to clarify the role of gliadin toxicity in the pathogenesis of gluten intolerance (celiac disease), previous in vitro studies have been based on two-dimensional human cell cultures. However, the specific morphological and biochemical properties of in vivo tissue are better maintained in three-dimensional cell cultures (multicellular spheroids, MCS). The aim of this study was to develop a three-dimensional in vitro model to investigate the effects of gliadin on epithelial cells and broaden our understanding of the early tissue damage occurring in celiac disease. METHODS: The three-dimensionally growing Lovo cell line was exposed to increasing concentrations of peptic-tryptic-digested bread wheat gliadin (from 125 to 1000 microg/mL) for 7 days in order to evaluate cell viability (colony-forming assay), and at the standard concentration of 500 microg/mL for 7 days in order to evaluate MCS diameters, volumes and cell morphology using light and electron microscopy. RESULTS: In comparison with the controls, the cell viability of the gliadin-treated MCS was significantly reduced (20-80%), but there was no difference in size. Various degrees of cell damage (autophagic vacuoles and intra-cytoplasmic lipid-like droplets) were detected by both light and electron microscopy. CONCLUSION: This is the first study investigating the effects of gliadin on MCS. Lovo MCS seem to be responsive to gliadin exposure, thus confirming previous results obtained using two-dimensional cell cultures. The data suggest that three-dimensional cell cultures may be useful in broadening our understanding of some of the early effects of gliadin peptides on epithelial cells.
Celiac disease is an intestinal disease due to an abnormal immuno-mediated response to gluten and other peptides from different cereals in genetically susceptible subjects. Several systemic alterations, including bone alterations, may be present in affected subjects. Once considered rare, it is now known to be quite frequent in both Europe and North America, as the recent availability of specific serological markers has drastically changed our perspective on its prevalence. The diagnosis of celiac disease may be very difficult because the clinical picture is highly variable and the characteristic intestinal signs and symptoms may be completely absent. Among the extra-intestinal alterations, bone mass decrease and bone metabolism derangement are frequently present and can be the only signs of an otherwise silent celiac disease. Clinical and epidemiological data are now plentiful but no conclusive data on the pathogenesis of bone involvement in celiac disease are available yet. Bone alterations were once thought to derive from calcium and vitamin D deficiency secondary to simple intestinal malabsorption, but now a more complex interaction between cytokines and local/systemic factors influencing bone formation and reabsorption is envisaged, Also, there is now substantial evidence supporting a lifelong gluten-free diet as the first-choice therapy for celiac disease, and as far as we know, this is the only effective measure to restore bone metabolism to an apparent normality. In the young, an early-started gluten-free diet can even lead to a satisfactory recovery of bone mass. In adults, however, there is no spontaneous recovery, and there are no conclusive data on the efficacy of standard therapies for osteoporosis in reducing the fracture risk. For these reasons, we feel that a review of the clinical findings on bone problems in celiac disease may be useful for both gastroenterologists and osteoporosis specialists.
The pathogenesis of celiac disease is not completely understood but, although the initial step of the process is still unclear, an altered immune response seems to play a major role. Previous studies of the biological properties of gliadin have highlighted its cytotoxic effects, and the aim of this study was to develop an in vitro technique to study them. The LoVo (human colon adenocarcinoma) cell line grown in two-dimensional cultures was exposed to different concentrations of digested bread wheat gliadin (62, 125, 250, 500 and 750 microg/ml) for 48 h, after which cell growth and oxidative balance (the content of reduced glutathione (GSH), and peroxidase, transferase and reductase activity) was evaluated. Other food proteins were used as controls. Our data revealed a statistically significant inhibition of cell growth in proportion to the gliadin concentration (from 26 to 100%), combined with a decrease in GSH content (-38% at 500 microg/ml) and reduced enzymatic activity (-30% at 500 microg/ml). The controls did not show any noxious effect. Our results confirm the usefulness of LoVo cells in evaluating gliadin cytotoxicity and that they can be used to investigate the biological properties of gliadin.
BACKGROUND: A possible link between coeliac disease and dilated cardiomyopathy has recently been suggested. AIMS: . To assess the frequency of anti-endomysial antibodies, the marker for coeliac disease, in patients with different forms of heart failure, and to establish the clinical features of those endomysial antibody positive. SUBJECTS AND METHODS: . A total of 642 consecutive patients entering the waiting list for heart transplantation from 1995 through 1997 were studied. The prevalence of endomysial IgA antibodies, determined by indirect immunofluorescence, was compared to that observed in three surveys conducted in the Italian general population. RESULTS: Of the 642 patients, 12 (1.9%; 95% confidence interval 0.97-3.2) resulted endomysial antibody positive, versus 34/9,720 healthy controls (0.35%; 95% confidence interval, 0.23-0.47), accounting for a relative risk of 5.3 (95% confidence interval, 2.8-10.3). Anti-endomysial antibodies were found in 6/275 patients with dilated cardiomyopathy and 6/367 with other forms of heart failure (2.2% versus 1.6%; 95% confidence interval 0.8-4.7 and 0.6-3.5), with no statistical difference. The 12 endomysial antibody positive patients were leaner (body mass index, 22.0 +/- 1.9 vs 24.2 +/- 3. 1, p<0. 05) than 36 seronegative patients matched for baseline demographics and aetiology of cardiomyopathy No differences were observed as regards clinical, biochemical and echocardiographic features, mortality in waiting list and 2-year post-transplant survival. CONCLUSIONS: Patients with end-stage heart failure are at increased risk for coeliac disease as compared to the general population.
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As available data on Helicobacter pylori infection in patients with diabetes are scattered and discordant, we evaluated the prevalence of H. pylori and its relationship to dyspeptic symptoms in adult patients with diabetes and subjects with dyspepsia. H. pylori infection (evaluated using the 13C urea breath test) and dyspeptic symptoms (nausea, bloating, and epigastric distress) were investigated in 71 consecutive diabetic outpatients; the presence of gross lesions, histologic gastritis, and Helicobacter was verified in the patients with a positive urea test who agreed to undergo upper gastrointestinal tract endoscopy. Seventy-one age- and gender-matched subjects with dyspepsia were used as controls. Helicobacter pylori infection was detected in 49 (69%) patients with diabetes and in 33 (46%) subject with dyspepsia (p = 0.007). Helicobacter pylori was present in 27 (77%) of 35 patients with diabetes with dyspeptic symptoms and in 22 (61%) of 36 patients without dyspeptic symptoms. Endoscopy revealed peptic ulcers in 13 of 23 patients; H. pylori infection was histologically confirmed in the gastric antrum of all patients with diabetes, and in the body of the stomach in 74%. The significantly higher prevalence of H. pylori infection in the patients with diabetes may partially explain their dyspeptic symptoms. The high prevalence of H. pylori infection, esophagitis, and peptic ulcers found in our patients with diabetes (with or without dyspepsia) suggests that this population should be considered "at risk" for H. pylori infection and suitable candidates for treatment.
BACKGROUND: Although 30% to 40% of patients with celiac disease (CD) (which affects 1 in 200 individuals) have dyspeptic symptoms, there is a lack o data concerning the prevalence of CD in patients with dyspepsia. METHODS: In this prospective series, we enrolled all consecutive outpatients undergoing endoscopy of the upper gastrointestinal tract for dyspepsia at our centers between January and June 1998. The exclusion criteria were age younger than 12 years, workup or follow-up of an already known disease of the gastrointestinal tract, suspected CD, malabsorption, and/or iron-deficiency anemia. RESULTS: Of the 3019 patients who were evaluated, 517 (17%) were eligible for the study. Endoscopic findings suggested CD in 5 cases. Celiac disease was histologically diagnosed in 6 patients (5 women and 1 man; mean age, 31.3 years; age range, 20-46 years), 3 of whom had a normal endoscopic pattern and 3 of whom had an endoscopic pattern that was consistent with CD. In the patients with histologically diagnosed CD, antiendomysium antibody positivity supported the diagnosis. The relative risk for CD was 2.32 (95% confidence interval, 1.06-5.07) in comparison with the general population and higher among females (3.22; 95% confidence interval, 1.37-7.56). CONCLUSIONS: The present results indicate that the prevalence of CD in patients with dyspepsia is twice that of the general population. Thus, serological screening for CD should be considered in the early workup of these patients to allow diagnosis and treatment of an eminently treatable disease.
BACKGROUND: Loss or reduction of duodenal folds, scalloping of Kerkring folds and a micronodular or mosaic duodenal mucosal pattern have been described in celiac disease (CD), endoscopic findings that are considered reliable in the diagnosis of this disorder. However, most data have been obtained in patients with suspected or certain disease. We assessed the accuracy of the above markers in diagnosing CD in patients with nonulcer dyspepsia. METHODS: In this prospective study, in 705 consecutive dyspeptic patients (284 men, 421 women, mean age 51 +/- SD 15.8 years) duodenal biopsies were obtained only in the presence of typical endoscopic markers, whereas in another 517 (207 men, 310 women, mean age 49.9 +/- SD 16 years) duodenal biopsies were done irrespective of macroscopic findings. CD was diagnosed histologically and on the basis of positive antiendomysium antibody. RESULTS: Endoscopic markers were found in 4 patients of the first group but CD was ruled out. In the second group 5 patients had an endoscopic pattern that was consistent and CD was diagnosed in 3, whereas 3 others with normal endoscopic findings were eventually diagnosed as having CD. Endoscopic markers had a sensitivity of 50% and a specificity of 99.6% (95% CI [11.8, 88.2 and 98.6, 99.9], respectively) with positive and negative predictive values of 60% and 99.4%, respectively. CONCLUSION: The accuracy of endoscopic markers in the diagnosis of CD must be reevaluated in relation to the characteristics of the population studied.
BACKGROUND: Upper gastrointestinal motor abnormalities could account for some of the dyspeptic symptoms of celiac patients. However, the data on gastric emptying time are conflicting, and the pathophysiology of motor disturbances is still unclear. Neurotensin modulates upper gastrointestinal motor activity, and its postprandial increase is a reliable index of nutrient delivery to the ileum. We therefore assessed both plasma neurotensin levels and gastric emptying in untreated celiacs. METHODS: The gastric antral area of nine untreated celiac patients and nine controls was measured with ultrasound at base line and every 30 min after a fatty meal (227 kcal, 45% fat); the base-line and postprandial neurotensin plasma levels were determined by means of radioimmunoassay. The data are mean values +/- standard deviation and were analyzed by using non-parametric tests. RESULTS: The overall and half gastric emptying time were significantly longer in the patients (203+/-32 versus 133+/-15 min, P = 0.0117, and 137+/-32 versus 78+/-11 min, P = 0.0001). The pattern of the changes in antral area was similar in both groups during the observation period as a whole but differed significantly in the first 120 min (P = 0.0343). Base-line neurotensin levels were significantly higher in the patients (41.6+/-23.9 versus 18.2+/-5.5 pg/ml, P = 0.0214) and their net postprandial increase was lower than in controls (15.0+/-15.9 versus 29.8+/-13.0 pg/ml, P = 0.046). In both groups the base-line neurotensin levels were related to the half gastric emptying time (P = 0.023). CONCLUSIONS: In untreated celiac patients gastric emptying time is longer than in controls and is concomitant with an increase in base-line plasma neurotensin levels.
BACKGROUND: Celiac disease responds to dietary gluten withdrawal, but data on the long-term effects of gluten-free diets are discordant. OBJECTIVE: Our aim was to evaluate the nutritional status and body composition of adult celiac disease patients consuming a gluten-free diet who were in clinical, biochemical, and histologic remission. DESIGN: We studied 71 patients (51 women and 20 men; mean age: 27 y; range: 17-58 y) and 142 healthy control subjects matched by sex and age. The subjects' height, weight, body mass index, fat and lean mass, and bone mineral content (evaluated by dual-energy X-ray absorptiometry) were measured; a 3-d dietary questionnaire was administered; and total daily energy, fat, carbohydrate, and protein intakes were calculated. RESULTS: The weight, height, and body mass index of male celiac disease patients and the weight and body mass index of female celiac disease patients were significantly lower than the corresponding measurements in control subjects. The fat and lean mass of both male and female patients was significantly different from that of control subjects; however, bone mineral content was significantly lower only in females in whom celiac disease was diagnosed in adulthood. Total energy intake was lower in the patients than in the control subjects (9686 +/- 1569 and 11297 +/- 1318 kJ/d in males and 6736 +/- 1318 and 7740 +/- 1715 kJ/d in females), and the diet of the patients was unbalanced, with a higher percentage of energy as fat and a lower percentage of energy as carbohydrates. CONCLUSIONS: Although strictly compliant with their gluten-free diet and in complete remission, patients with celiac disease showed differences in body composition and dietary intakes compared with control subjects. Strict follow-up and dietary advice in terms of the choice and composition of foods seem necessary to prevent malnutrition.
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OBJECTIVE: The aim of this study was to investigate the role of genetic factors and the characteristics of five monozygous twin pairs with at least one member affected by gluten sensitivity. METHODS: Five pairs of monozygous female twins, of whom one or both were affected by gluten sensitivity (i.e., celiac disease or dermatitis herpetiformis), were followed-up for 11-23 yr. RESULTS: Three pairs were concordant for celiac disease: the onset was comparable and synchronous in two pairs; in the third, one member presented an overt malabsorption syndrome, and the other developed iron deficiency anemia 10 yr later. Discordance for gluten sensitivity was found in the remaining two pairs, one of whose members was diagnosed as having, respectively, celiac disease and dermatitis herpetiformis. CONCLUSIONS: As no environmental factors were found to affect the phenotypic expression of the disease, genetic factors seem to play a major role. The presence of overt or latent celiac disease in three of the four siblings of the three concordant twins, and the association with cystic fibrosis in all three siblings of one of these families, further supports this hypothesis.
BACKGROUND: An association between alopecia areata (AA) and coeliac disease has recently been reported. AIM: The aim of this paper was to evaluate the possible effect of a gluten-free diet (GFD) on the new growth of hair in 5 alopecic patients with CD. METHODS: CD was diagnosed in 5 patients with AA (universalis in 3 cases and patchy in 2 cases). The diagnosis of CD was based on serological and histological standard criteria. RESULTS: In all patients the GFD resolved CD clinically, serologically and histologically but had no effect on the course of alopecia. CONCLUSION: AA and CD, when associated, present different responses to a GFD and have an independent course.