Carola Severi

Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors.

Background: Chromogranin A (CgA) is considered the most accurate marker in the diagnosis of gastro-entero-pancreatic (GEP) endocrine tumors. Pancreatic polypeptide (PP) has also been proposed to play this role, but then not used due to its low sensitivity. The aim of the present study was to determine whether the assessment of PP would improve the diagnostic reliability of CgA in patients with GEP tumors. Patients and methods: Both markers were assessed in 68 patients [28 functioning (F), 40 non functioning (NF)]. Twenty-seven patients disease-free (DF) after surgery, and 24 with non-endocrine tumors (non-ETs) were used as control groups. Results: CgA sensitivity was: 96% in F, 75% in NF, 74% in pancreatic, and 91% in gastrointestinal (GI) tumors. Specificity was 89% vs DF, and 63% vs non- ETs. PP sensitivity was: 54% in F, 57% in NF, 63% in pancreatic, and 53% in GI tumors. Specificity was 81% vs DF, and 67% vs non-ETs. By combining the two markers a significant gain in sensitivity vs CgA alone was obtained: overall in GEP tumors (96% vs 84%, p=0.04), in NF (95% vs 75%, p=0.02), and in pancreatic (94% vs 74%, p=0.04). More specifically, a 25% gain of sensitivity was obtained in the subgroup of NF pancreatic tumors (93% vs 68%, p=0.04). Conclusion: The combined assessment of PP and CgA leads to a significant increase in sensitivity in the diagnosis of GEP tumors, particularly in pancreatic NF.

Reassessment of Intrinsic Factor and Parietal Cell Autoantibodies in Atrophic Gastritis With Respect to Cobalamin Deficiency

OBJECTIVES:Atrophic body gastritis (ABG) is an autoimmune condition eventually manifesting itself as pernicious anemia (PA). Parietal cell autoantibodies (PCAs) and intrinsic factor autoantibodies (IFAs) are considered characteristics of these conditions. Recent studies on IFA and PCA frequency with respect to cobalamin deficiency in biopsy-proven ABG patients are lacking. We addressed this issue using new enzyme-linked immunosorbent assay (ELISA)-based assays.METHODS:Sera from 165 patients with histologically diagnosed ABG and 113 controls were tested for IFA and PCA using ELISA. A total of 81 ABG patients had cobalamin deficiency and macrocytic anemia (Group 1-PA), 36 had cobalamin deficiency without macrocytic anemia (Group 2), and 48 had normal cobalamin levels (Group 3).RESULTS:IFAs were detected in 44/165 ABG patients (27% sensitivity) and in 0/113 controls (100% specificity). PCAs were detected in 134 ABG patients (81% sensitivity) and in 11 controls (90% specificity). In Group 1, IFAs showed 37% sensitivity and 100% specificity, whereas PCAs showed 81% sensitivity and 90% specificity. Combining IFA and PCA testing increased the sensitivity to 61% in all ABG patients and to 73% in Group 1, while maintaining 100% specificity.CONCLUSIONS:IFAs are 100% specific for biopsy-proven ABG and occurred in 27% of patients. PCAs occurred in 81% of ABG patients and in 10% of controls. Combining IFA and PCA testing significantly increases their diagnostic performance for ABG and PA, yielding a 73% sensitivity for PA. The non-invasive combined PCA and IFA assessment may be useful in selecting patients at risk for autoimmune gastritis to be confi rmed by gastroscopic–histologic examination.

Bombesin effects on human GI functions.

In this article some of the actions of amphibian skin peptide Bombesin (BBS) on human gastrointestinal and pancreatic functions are reviewed. BBS causes increases of lower esophageal sphincter pressure, delay of gastric emptying, inhibition of mechanical activity of duodenum and jejunum and gallbladder emptying. BBS also releases in man gastrin and stimulates gastric acid secretion. BBS administration induces release of insulin, glucagon and pancreatic polypeptide from human Islet of Langerhans and causes secretion of pancreatic bicarbonates and enzymes in duodenal juice and release of pancreatic enzymes in blood stream.

Effects of bombesin on gastrin and gastric acid secretion in patients with duodenal ulcer

The effect of bombesin, a possible neurotransmitter of gastrin release, upon gastrin and gastric acid secretion was investigated in 25 patients with duodenal ulcer and in 16 normal subjects. In patients with duodenal ulcer bombesin (10 ng/kg/min) produced an increase in plasma gastrin output (median 22·4 (range 7·5-75·8) pmol/l/min) similar to that obtained in normal subjects (median 24·4 (range 5·8-56·5) pmol/l/min), whereas gastrin stimulated by a meal was significantly higher in the group of patients with duodenal ulcer (median 20·7 (range 9·2-42·9) vs 16·2 (range 3·4-22·2) p<0·05). Peak acid output induced by bombesin was significantly higher in patients with duodenal ulcer than in normal subjects (median 24·4 (range 9·0-63·8) vs 14·0 (range 3·0-24·8) mmol/h, p<0·05) despite identical gastrin outputs. The ratio (%) obtained by dividing the acid secretory response to bombesin by the response to pentagastrin, however, was similar in both normal subjects and patients with duodenal ulcer (median 55 (range 20-116) vs 58 (range 31-95) respectively). The difference between the gastrin response to food and bombesin could be explained by the fact that bombesin releases gastrin directly, whereas a protein meal involves several mechanisms (neural, peptidergic, paracrine, endocrine), either stimulatory or inhibitory. The above results indicate that a higher concentration in antral and/or duodenal gastrin is unlikely to be present in patients with duodenal ulcer. An increased parietal cell mass could explain the higher gastric acid response after bombesin infusion in our group of patients with duodenal ulcer.

Exposure of Toll-Like Receptors 4 to Bacterial Lipopolysaccharide (LPS) Impairs Human Colonic Smooth Muscle Cell Function

Endotoxemia by bacterial lipopolysaccharide (LPS) has been reported to affect gut motility specifically depending on Toll‐like receptor 4 activation (TLR4). However, the direct impact of LPS ligation to TLR4 on human smooth muscle cells (HSMC) activity still remains to be elucidated. The present study shows that TLR4, its associated molecule MD2, and TLR2 are constitutively expressed on cultured HSMC and that, once activated, they impair HSMC function. The stimulation of TLR4 by LPS induced a time‐ and dose‐dependent contractile dysfunction, which was associated with a decrease of TLR2 messenger, a rearrangement of microfilament cytoskeleton and an oxidative imbalance, i.e., the formation of reactive oxygen species (ROS) together with the depletion of GSH content. An alteration of mitochondria, namely a hyperpolarization of their membrane potential, was also detected. Most of these effects were partially prevented by the NADPH oxidase inhibitor apocynin or the NFκB inhibitor MG132. Finally, a 24 h washout in LPS‐free medium almost completely restored morphofunctional and biochemical HSMC resting parameters, even if GSH levels remained significantly lower and no recovery was observed in TLR2 expression. Thus, the exposure to bacterial endotoxin directly and persistently impaired gastrointestinal smooth muscle activity indicating that HSMC actively participate to dysmotility during infective burst. The knowledge of these interactions might provide novel information on the pathogenesis of infection‐associated gut dysmotility and further clues for the development of new therapeutic strategies. J. Cell. Physiol. 223: 442–450, 2010.

Role of Noninvasive Tests (13C-Urea Breath Test and Stool Antigen Test) as Additional Tools in Diagnosis of Helicobacter Pylori Infection in Patients with Atrophic Body Gastritis

Background.  Detection of Helicobacter pylori infection in atrophic body gastritis (ABG) is difficult, as during progression of body atrophy, H. pylori disappears.

Helicobacter pylori infection in obesity and its clinical outcome after bariatric surgery

The present review summarizes the prevalence and active clinical problems in obese patients with Helicobacter pylori (H. pylori) infection, as well as the outcomes after bariatric surgery in this patient population. The involvement of H. pylori in the pathophysiology of obesity is still debated. It may be that the infection is protective against obesity, because of the gastritis-induced decrease in production and secretion of the orexigenic hormone ghrelin. However, recent epidemiological studies have failed to show an association between H. pylori infection and reduced body mass index. H. pylori infection might represent a limiting factor in the access to bariatric bypass surgery, even if high-quality evidence indicating the advantages of preoperative H. pylori screening and eradication is lacking. The clinical management of infection is complicated by the lower eradication rates with standard therapeutic regimens reported in obese patients than in the normal-weight population. Prospective clinical studies to ameliorate both H. pylori eradication rates and control the clinical outcomes of H. pylori infection after different bariatric procedures are warranted.

CagA and VacA are Immunoblot Markers of Past Helicobacter pylori Infection in Atrophic Body Gastritis

Background and Aim:  Atrophic body gastritis (ABG) may be induced by H. pylori infection. It is difficult to diagnose H. pylori infection in this condition, since during progression of body atrophy the bacterium disappears. In 30% of patients with ABG no sign of H. pylori infection is detectable. We aimed to investigate whether patients with ABG, classified as H. pylori‐negative by conventional methods (ELISA serology and Giemsa stain histology), have been previously exposed to the infection.

Effect of acute mucosal exposure to Lactobacillus rhamnosus GG on human colonic smooth muscle cells.

Aim To define whether human colonic mucosa exposure to Lactobacillus rhamnosus GG (LGG), American Type Culture Collection (ATCC) 53103, may influence intestinal muscle cell contractility. Methods Human colon specimens were obtained from disease-free margins of resected segments for cancer. The mucosa and submucosa, after dissection, were sealed between 2 chambers, with the luminal side of the mucosa facing upward and covered with 5 mL of Krebs solution and the submucosal side facing downward into 20 mL of Krebs solution. LGG or normal undernatant (N-undernatant) were added to the luminal side of the mucosa for 30 minutes. Smooth muscle cells (SMCs), isolated from the circular muscle layer, were exposed to undernatant for 30 minutes from the submucosal chamber of mucosa that was either preexposed to N-undernatant or to LGG (36×10−9 colony forming units/mL) (LGG-undernatant). Acetylcholine (Ach) dose-response was obtained for SMCs. Results SMCs exposed to N-undernatant presented a dose-response to Ach (maximal contraction: 32%±5% with 1-μM Ach) that is similar to unstimulated SMCs. Exposure to LGG-undernatant resulted both in an 18%±3% cell shortening and a 78%±7% inhibition of maximal Ach-induced contraction. When SMCs were directly exposed to LGG, a significant impairment of contraction (70%±5%, compared with control cells) and a dose-dependent and time-dependent shortening were observed. Conclusions After acute exposure of colonic mucosa to LGG, a significant shortening of SMCs is observed that possibly contributes to the reduced contractile response to Ach. Further studies are needed to establish the mechanisms of this effect that could account for the clinical efficacy of probiotics in intestinal disorders.

Postbiotic activities of lactobacilli-derived factors.

Probiotics are alive nonpathogenic microorganisms present in the gut microbiota that confer benefits to the host for his health. They act through molecular and cellular mechanisms that contrast pathogen bacteria adhesion, enhance innate immunity, decrease pathogen-induced inflammation, and promote intestinal epithelial cell survival, barrier function, and protective responses. Some of these beneficial effects result to be determined by secreted probiotic-derived factors that recently have been identified as “postbiotic” mediators. They have been reported for several probiotic strains but most available literature concerns Lactobacilli. In this review, we focus on the reported actions of several secretory products of different Lactobacillus species highlighting the available mechanistic data. The identification of soluble factors mediating the beneficial effects of probiotics may present an opportunity not only to understand their fine mechanisms of action, but also to develop effective pharmacological strategies that could integrate the action of treatments with live bacteria.