P. Giorgio

Duodenogastric Reflux of Bile Acids, Gastrin and Parietal Cells, and Gastric Acid Secretion before and 6 Months after Cholecystectomy

In order to evaluate the effect of cholecystectomy on the gastric mucosa, the duodenogastric reflux of total and single bile acids, the number of parietal and gastrin cells, and the volume of gastric acid secretion were examined in 15 patients with gallstones and functioning gallbladders before and 6 months after cholecystectomy. The duodenogastric reflux of the total bile acids increased from a mean preoperative value of 1.9 mumol/hour to a mean postoperative value of 21 mumol/hour (p = 0.008). The duodenogastric reflux of all single bile acids increased after cholecystectomy, with a higher increase in glycoconjugated compared with tauroconjugated bile acids. The parietal cells decreased from a mean preoperative value of 82.8 to a mean postoperative value of 68.7 (p = 0.05), whereas there was only a mild increase in the number of gastrin cells; the output of gastric acid remained unchanged. The variation of the gastrin cells before and after cholecystectomy was negatively correlated only with the variation of taurocholic acid (r = -0.50, p = 0.05), while the variation of the parietal cells was mildly correlated with all single bile acids (r = 0.35-0.50, 0.05 less than p less than 0.02). These findings show an increased duodenogastric reflux of bile acids 6 months after cholecystectomy with a mild morphologic alteration of the gastric mucosa.

Differential expression of multiple transglutaminases in human colon: impaired keratinocyte transglutaminase expression in ulcerative colitis

Background and aims: Ulcerative colitis (UC) is characterised by refractory inflammatory ulceration and damage to the colon. The mechanisms underlying impaired healing have yet to be defined. As transglutaminase expression resulting in matrix protein cross linking is associated with increased wound healing in a rat model of colitis, we hypothesised that different types of transglutaminase might also play a role in UC. Patients and methods: Endoscopic and histological indices were studied in 26 patients with UC (10 active and 16 inactive) and in 20 normal controls undergoing colonoscopy. Transglutaminase activity was evaluated in plasma (factor XIIIa) by a radioenzymatic method. Factor XIIIa, tissue and keratinocyte transglutaminase protein content, and mRNA expression in the colon were evaluated by western blot analysis and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively. Colonic location of transglutaminases and their reaction products, the ε-(γ-glutamyl)lysine bonds, was evaluated by immunohistochemistry using specific monoclonal antibodies. Results: Transglutaminase activity was significantly lower in the plasma of patients with active UC (4.2 (2.4) mU/ml; p<0.05 v controls) than in those with inactive UC and controls (10.6 (2.2) and 12.1 (1.7) mU/ml). As shown by western blot, protein levels of tissue transglutaminase and factor XIIIa were unchanged in active UC compared with inactive disease and controls, while the keratinocyte form was reduced in active UC. Tissue transglutaminase and factor XIIIa immunostaining was strongly present in damaged areas colocalising with isopeptide bonds. In contrast, the keratinocyte form was almost absent in active UC and localised in the upper part of the crypts in normal subjects. RT-PCR showed upregulation of tissue transglutaminase mRNA in active UC (320% compared with controls) while keratinocyte transglutaminase gene expression was downregulated in active UC. Conclusions: The results of the present study support the concept that, in the damaged colon, transglutaminases are needed in response to chronic injury and underline the key role of these enzymes in mucosal healing.

Low presence of p53 abnormalities in H. pylori-infected gastric mucosa and in gastric adenocarcinoma

Background: Alterations of the p53 gene and/or its abnormal protein accumulation have been observed in gastric cancer and preneoplastic lesions. Our aim was to assess possible associations between different H. pylori strains and p53 abnormalities in patients with dyspepsia and with gastric cancer. Methods: Seventy-five dyspeptic patients and 40 patients with gastric adenocarcinoma entered the study. H. pylori status was determined by the rapid urease test, histology, and polymerase chain reaction (PCR) analysis. Overexpression of the p53 protein was evaluated by immunohistochemistry. Detection of p53 mutations was done by direct DNA sequencing. Results: Fifty-four of the 75 (72.0%) dyspeptic patients and 27 of the 40 (67.5%) gastric cancer patients showed H. pylori infection. Cytotoxin-associated gene (cagA)-positive strains were found in 31 of the 54 (58%) dyspeptic patients and in 25 of the 27 (92.6%) neoplastic patients. As regards vacA, s2 strains showed the highest prevalence among dyspeptic patients (24 of 54 patients; 44.4%), whereas s1 strains were more expressed among cancer patients (23 of 27; 85.2%). Among the dyspeptic patients, 1 patient with duodenal ulcer showed p53 overexpression. Three mutations were identified by DNA sequencing: one in a patient with normal endoscopic findings and two in patients suffering from gastritis. Among the neoplastic patients, 16 subjects (40%) showed p53 overexpression (9 had diffuse-type and 7 intestinal-type cancer). Four mutations (10%) occurred in patients with intestinal-type gastric cancer. No association between p53 abnormalities (overexpression/mutation) and H. pylori infection was found in either group of patients. Conclusions: These results lead us to hypothesize that H. pylori infection does not affect the p53 pattern in gastric mucosa. Moreover, mutations of the p53 gene do not seem to be a predominant event in gastric carcinogenesis, at least in our populations.

Helicobacter pylori strains and histologically-related lesions affect the outcome of triple eradication therapy: a study from southern Italy

Background : Certain evidence suggests that Helicobacter pylori strains expressing genes for cytotoxin production show a higher sensitivity than non‐cytotoxic organisms to eradication treatment. No data are available on the involvement of bacterium‐related lesions in different therapeutic outcomes.