Gastrokine 1 expression in patients with and without Helicobacter pylori infection.

BACKGROUND: To understand the molecular changes underlying Helicobacter pylori-related gastric diseases is mandatory to prevent gastric cancer. Proteomic technology is providing a rapid expansion of the basic knowledge, particularly in the discovery of new biomarkers involved in the tumourigenesis. AIM: To characterise changes in protein expression level of the gastric mucosa in H. pylori-infected patients. METHODS: The population enrolled comprised 41 dyspeptic patients. Proteins extracted from gastric mucosal specimens were analysed by 2-dimensional electrophoresis, sequenced by MALDI-TOF and identified by Edman's degradation. RESULTS: Twenty-one out of 41 patients had H. pylori infection of whom 17 had anti-CagA IgG antibodies. Several proteins were identified, of which Rho guanosine diphosphatase dissociation inhibitor alpha and heat shock protein 27 increased and glutathione transferase and antrum mucosa protein-18 decreased in H. pylori-positive in respect to H. pylori-negative patients. Interestingly, antrum mucosa protein-18, currently referred as gastrokine-1, showed two isoforms differing in the first N-terminal amino acid residue. Both gastrokine-1 isoforms were observed in the H. pylori-negative group whereas a lower expression or even absence of the gastrokine-1 basic isoform was found in a subgroup (7/21) of H. pylori-positive patients with moderate-severe gastritis. CONCLUSION: Our study demonstrated the presence of gastrokine-1 isoforms of which the basic isoform was reduced in a subset of patients with H. pylori infection.

Essential hypertension and chronic viral hepatitis.

OBJECTIVE: Both arterial hypertension and chronic hepatitis are common disorders. The relationship between arterial pressure and liver cirrhosis has been extensively studied, but no studies are available in chronic hepatitis (CH). Recently, a few studies have reported that treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs), commonly used in arterial hypertension, reduce hepatic fibrosis in patients with viral CH and in nonalcoholic steatohepatitis. This study was aimed at comparing the evolution of post-viral CH in patients with/without concomitant essential hypertension. METHODS: Two sets of observations were carried out: (a) a cross-sectional cohort study of 95 patients with viral CH, to compare the severity of histological and biochemical data at diagnosis, in relation to pharmacologically treated essential hypertension, and (b) a retrospective study with the observation of 254 patients with CH of viral etiology, followed up from 2 to 20 years, to establish the natural history of viral CH in relation to treated essential hypertension. RESULTS: In the cross-sectional analysis, patients with treated hypertension had a significantly older age at diagnosis of CH (51.4 +/- 8.4 years vs. 46.2 +/- 12.2 in normotensive; P < 0.001) and histological evidence of less severe necro-inflammatory liver damage. ALT levels were also lower (109.8 +/- 62.5 U/L vs. 166.0+/-169.5 in normotensive; P < 0.001) as were endothelin-1 levels (0.74 +/- 0.97 vs. 1.77 +/- 1.51 fmol/mL; P < 0.001). The retrospective study confirmed an older age at diagnosis in patients with treated hypertension (48.7 +/- 9.8 vs. 41.9 +/- 11.8 years; P < 0.001) and lower death rates (2.2% vs. 11%; P < 0.05). CONCLUSIONS: The evolution of post-viral CH seems to be less severe in subjects with essential hypertension, possibly in relation to treatment with antihypertensive drugs.

Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias.

BACKGROUND: Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes. AIM: To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro-oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms. METHODS: Thirty-two patients (13 females and 19 males; age: 20-69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43-58 years) with GERD only, underwent simultaneous 24-h pH-metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months full-dosage PPI therapy (esomeprazole 40 mg/day) was prescribed. RESULTS: In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P < 0.05) correlation between oesophageal pH and LF/HF ratio (oesophagus-heart correlation) was observed. A significant reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs. 4/11, P < 0.01). CONCLUSIONS: This study has identified a subgroup of dysrhythmic patients in whom the oesophageal acid stimulus elicited cardiac autonomic reflexes. In these patients acid suppression seems to improve GERD and cardiac symptoms.

Cryptic epitopes on alpha-fetoprotein induce spontaneous immune responses in hepatocellular carcinoma, liver cirrhosis, and chronic hepatitis patients.

To determine alpha-fetoprotein (AFP) immunogenicity in vivo, the presence of antibodies in sera of 60 hepatocellular carcinoma, 15 liver cirrhosis, and 15 chronic hepatitis patients was evaluated by Western blotting and immunoprecipitation analyses using purified human AFP. High titers of anti-AFP immunoglobulins were detected in 14 hepatocellular carcinomas (P = 0.0006), 3 liver cirrhosis (P = 0.0173), and 1 chronic hepatitis patient, but they were not detected in 40 healthy individuals. Therefore, spontaneous immune responses to AFP are significantly associated to liver diseases (P = 0.0015). Patient immunoglobulins recognized proteic linear epitopes that were cryptic in the native protein, as demonstrated by their restricted reactivity with denatured deglycosylated AFP. Thus, in pathological liver conditions, tolerance to this self-molecule is circumvented. The identification of AFP immunogenic epitopes may contribute to defining novel immunotherapeutic strategies targeting this antigen.

Effects of anthracycline therapy on intestinal absorption in patients with advanced breast cancer.

Although cytotoxic chemotherapy for human cancer has been reported to induce alterations in intestinal permeability, its effects on the absorptive process are still controversial. We have studied mediated and nonmediated absorption in 10 patients with metastatic breast cancer before and after treatment with Adriamycin by the use of specific test sugars given orally and their subsequent urinary recovery, as measured by chromatography. Mediated absorption was investigated by the use of D-xylose and 3-O-methylglucose, while lactulose and L-rhamnose were used to study nonmediated permeation. Lactulose is considered a marker of unmediated paracellular (tight junction) permeation, while L-rhamnose explores passage across cell membranes. The test was performed on patients before and on the second and the eighth days after Adriamycin administration, and only once in 22 age-matched healthy women. Under basal conditions, as well as 2 and 8 days after chemotherapy, D-xylose and 3-O-methylglucose absorption was 35% lower in patients than in controls (P less than 0.001). Lactulose absorption was significantly higher in patients than in controls under basal conditions (P less than 0.001); it reached levels three times higher the second day after chemotherapy, and returned to basal levels by the eighth day. The data suggest an early reversible effect of Adriamycin on cellular tight junctions with resulting increased permeabilization. This effect seems of a toxic nature rather than due to increased cell loss. It is interesting that both nonmediated absorption and mediated absorption were already altered before chemotherapy in cancer patients, suggesting a preexisting functional damage of the intestine. The significance of this alteration as a potential mechanism of cancer cachexia is discussed.

Diagnostic accuracy of the serum profile of gastric mucosa in relation to histological and morphometric diagnosis of atrophy.

BACKGROUND: Histology is the gold standard for diagnosis of atrophy but is hampered by observer variation. A reliable method to overcome this issue is morphometric analysis of gastric mucosa. Serum pepsinogens and gastrin have been proposed in the diagnostic work-up of gastric atrophy although diagnostic accuracy of these tests is considered unsatisfactory. AIM: To evaluate the diagnostic accuracy of gastric serum profile in relation both to morphological and morphometric diagnosis of gastric atrophy. METHODS: Ninety-four dyspeptic out-patients underwent upper endoscopy and evaluation of serum levels of PGI, PGII and 17-gastrin. Diagnostic accuracy of gastric serum profile was tested by receiver operating characteristic curves and by evaluation of sensitivity and specificity in relation to both histology and morphometric analyses. RESULTS: As far as concern to histological evaluation, only PGI/PGII ratio showed an acceptable diagnostic accuracy in discrimination of gastric atrophy, while, when morphometric analysis was considered as reference, both serum PGI level and PGI/PGII ratio showed an excellent performance. However, both PGI and PGI/PGII ratio showed low sensitivity and high specificity. CONCLUSIONS: Serological gastric profile corresponds better with the morphometric diagnosis of atrophy, even if, because of the low sensitivity, today this could only be used as screening test of chronic atrophic gastritis.

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism. Multicentre prospective study by the 'Nutritional Problems in Gastroenterology' Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.

Is there a link between environmental factors and a genetic predisposition to cancer? A lesson from a familial cluster of gastric cancers.

To determine the prevalence of gastric precancerous lesions and mucosal genetic alterations in relatives of a cluster of familial gastric cancer (FGC), we studied a kindred spanning two generations. The founder, daughter and niece underwent surgery for gastric cancer (GC); a son and other two daughters of the founder, presented with chronic dyspepsia. In all subjects, gastric mucosa samples were analysed for pathological features, Helicobacter pylori infection, microsatellite (MIN) and chromosomal (CIN) instability. The overexpression of mp53 and c-myc, and cytoplasmic beta-catenin delocalisation were found in the 2 younger cancer patients. All GC and gastritis patients had normal E-cadherin expression and were MIN-negative. Aneuploidy characterised all GC cases, and mixed euploid and aneuploid cell populations were present in the gastric biopsies from two of three 'at-risk' relatives. These two subjects, one of whom had severe active gastritis, and gastric mp53 and c-myc expression, were CagA-positive H. pylori-infected. DNA aneuploidy, p53 and c-myc expression disappeared after H. pylori eradication. In this FGC cluster, genetic abnormalities were found in first-degree relatives (3 patients) only in presence of H. pylori infection (2 cases H. pylori-positive versus 1 case H. pylori-negative) supporting the hypothesis that, besides the influence of a genetic profile, FGC may be, at least partly, mediated by intrafamilial clustering of H. pylori infection.

The efficacy of octreotide therapy in chronic bleeding due to vascular abnormalities of the gastrointestinal tract.

BACKGROUND: The treatment of angiodysplasia and watermelon stomach, vascular abnormalities implicated in gastrointestinal bleeding of obscure origin, is a major clinical problem. AIM: To determine the efficacy of octreotide in patients with long-standing gastrointestinal bleeding due to acquired angiodysplasia and watermelon stomach, resistant to previous treatments and not suitable for surgery because of old age and/or concomitant disorders. PATIENTS AND METHODS: We treated 17 patients (seven had isolated angiodysplasia, seven had multiple upper and lower gastrointestinal angiodysplasia, and three had watermelon stomach) with octreotide (0. 1 mg subcutaneous t.d.s. for 6 months). Six of the patients had liver cirrhosis, one had Glanzmann-type platelet derangement, two had cardiovascular diseases and one had chronic uraemia. RESULTS: Octreotide treatment stopped bleeding in 10 patients. A transient improvement was observed in four, who needed subsequent cyclical retreatment to correct low haemoglobin levels. No effect was observed in three, probably due to the severity of the concomitant disorders. CONCLUSIONS: Octreotide is a safe drug that may be useful to control the recurrent gastrointestinal bleeding due to acquired angiodysplasia and watermelon stomach, especially in patients who are not candidates for surgery due to old age and/or concomitant disorders.

Lymphoblastoid interferon in chronic hepatitis C patients who were "non responders" to recombinant interferon alpha (rIFN alpha).

The aim of this study was to investigate whether there is a variable responsiveness of the hepatitis C virus and/or of the affected host to different types of interferon. We treated 21 patients affected by chronic hepatitis C who failed to respond to recombinant alpha interferon, after a four-month interval, with lymphoblastoid interferon. Alanine transaminase (ALT) serum level was normal in 9 patients (43%) at the end of treatment. At the end of a 12 months treatment-free follow-up serum ALT remained normal in 3 patients, 4 patients relapsed and 2 dropped-out. As yet there are no reports of differences in the therapeutic efficacy of the two types of interferon used in our study. The good response to the lymphoblastoid interferon in our non responders to recombinant alpha interferon may be due to the immune modulation induced by the four-month wash-out interval between the two therapies or to a different virus sensitivity to this interferon.

Diagnostic efficiency in discriminating liver malignancies from cirrhosis by serum gamma-glutamyltransferase isoforms.

Total GGT and GGT complexed with low-density-lipoprotein plus very low-density lipoprotein (LDL + VLDL) have been evaluated in sera from 53 healthy subjects, 23 patients with chronic hepatitis, 87 with liver cirrhosis and 50 with liver tumors (primary and metastatic). A cut-off of 20 U/l of GGT complexed with LDL + VLDL results in a diagnostic sensitivity of 84% for liver tumor patients, and a diagnostic specificity of about 80% towards the two groups of patients affected by cirrhosis or chronic hepatitis. This test, because of its high diagnostic efficiency, is a useful addition to the battery of laboratory tests that serve to discriminate cirrhosis and chronic hepatitis from liver malignancies.

An unusual case of ascites.

A 76-year-old woman with abdominal pain and diarrhoea developed ascites that did not respond to treatment. There were no signs of liver damage. Abdominal ultrasonography with colour Doppler revealed an arterial-like flow in the enlarged splenic vein. Using selective mesenteric arteriography, we were able to diagnose a shunt between the inferior mesenteric artery and the inferior mesenteric vein. This is an unusual case of ascites due to prehepatic portal hypertension secondary to an extrahepatic arterioportal fistula.

Acid exposure and altered acid clearance in GERD patients treated for Helicobacter pylori infection.

BACKGROUND: After the eradication of Helicobacter pylori, an increased incidence of gastroesophageal reflux disease and acid gastric secretion have been reported. AIM: To evaluate the effect of Helicobacter pylori-eradication on proximal and distal gastroesophageal reflux and acid clearance in patients with gastroesophageal reflux disease. PATIENTS AND METHODS: Sixty-eight gastroesophageal reflux disease patients (age range 18-61 years) were studied by upper endoscopy. All underwent esophageal manometry and dual probe 24-h pH-metry. RESULTS: Percent of time at pH<4 was significantly increased in the proximal esophagus of Helicobacter pylori-eradicated patients compared to Helicobacter pylori-negative (2.4+/-0.5 vs. 1.0+/-0.2; p<0.01); no differences were found in the distal esophagus (14.0+/-3.7 vs. 9.0+/-1.4%, NS). The total number of reflux episodes was significantly higher in the proximal oesophagus of Helicobacter pylori-eradicated patients (37+/-3 vs. 22+/-3, p<0.05). In the distal esophagus, acid clearance was significantly longer, both during total time (1.4+/-0.2 vs. 0.8+/-0.7 min, p<0.01), and in the supine period (8.5+/-2.7 vs. 2.7+/-0.4 min, p<0.05). No differences were reported in the manometric parameters of the two groups of patients. CONCLUSION: In patients with gastroesophageal reflux disease, Helicobacter pylori eradication is associated with increased acid exposure of the proximal esophagus and delayed distal acid clearance.

Effect of Helicobacter pylori infection on gastric cell proliferation and genomic instability in a paediatric population of southern Italy.

BACKGROUND: The incidence of gastric cancer is high in areas with a high prevalence of Helicobacter pylori infection. Cell transformation and tumour progression occur over a long period of time and markers of genomic instability usually precede morphological changes. AIM: To evaluate the effect of Helicobacter pylori infection on cell proliferation, DNA status and oncogene expression in children. PATIENTS AND METHODS: Morphometric and immunohistochemical techniques were used to analyse DNA content, p53 and c-myc oncogene expression and cell proliferation on gastric biopsies of 53 children (27 Helicobacter pylori-negative and 26 Helicobacter pylori-positive). RESULTS: Gastric mucosa was normal in 11% of Helicobacter pylori-positive and in 33% of Helicobacter pylori-negative subjects. Most children had chronic non-atrophic gastritis regardless of Helicobacter pylori infection, and only a minority of children affected by Helicobacter pylori had mild atrophic gastritis. Cell proliferation was significantly higher in children with Helicobacter pylori-positive gastritis than in those with Helicobacter pylori-negative gastritis. No metaplasia, dysplasia, p53 overexpression or altered DNA content was found in any child. Interestingly, 46% of children with and 29% without Helicobacter pylori infection had c-myc overexpression closely related to the cell proliferation rate. CONCLUSION: Helicobacter pylori infection in children may coexist with a normal gastric mucosa, and it is not associated with genomic instability markers in cases of chronic gastritis.

Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemia) and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey.

BACKGROUND: Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. AIM: To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. PATIENTS AND METHODS: This retrospective, cross-sectional study involved 1,195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. RESULTS: Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. CONCLUSIONS: This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.

Clinical nutrition practice in Italian Gastroenterology Units.

BACKGROUND: Nutritional status affects the course, ensuing complications and prognosis of virtually all diseases. AIMS: To define the role of nutrition in Gastroenterology Units by means of two investigations that analyse: a) availability of devices for assessing nutritional status; b) nutritional treatment in clinical practice: incidence and frequency of indications for its use, together with type of treatment adopted. PATIENTS AND METHODS: Two questionnaires were sent to Italian Academic and Hospital Gastroenterology Units, all with clinical wards. RESULTS: Results refer to 27 Units, 22 of which took part in both parts of the analysis, enrolling 547 patients during the two-week study The first analysis shows that scales and the altimeter are not available everywhere, while more specific tools, such as skinfold calipers are available in 54% of the Units, and caloric intake can be assessed in 22-41%. The second analysis reveals that nutritional treatment was necessary in 50% of patients in the series examined, and that this was taken into account and prescribed in almost all cases (91%). Of the patients treated, 69% received dietetic supplementation and 31% artificial nutrition [12% enteral, 88% parenteral), although supportive parenteral nutrition is often contraindicated in conditions where good bowel function provides the conditions for enteral nutrition. CONCLUSION: Data emerging from the investigation showed that i) artificial nutrition is commonly used in gastroenterology Units in Italy although 23% of them never consider either enteral or parenteral nutrition as medical treatment of gastrointestinal disease; ii) malnutrition is a very frequent complication (mean 27%; range 4-55%0) in Gastroenterology Unit patients albeit only 42% of malnourished patients received artificial nutrition; iii) indications for enteral and parenteral nutrition are not always respected, as there is an excessive use of parenteral nutrition and an unjustified resistance to the use of enteral nutrition; iv] nutritional treatment is often administered without adequate nutritional assessment and without a complete adherence to the standards recommended for preparation of parenteral bags, supported by suitable technology; v) only two Gastroenterology Units report admitting and following patients in a home parenteral nutrition programme; vi) this investigation probably reflects the response of those Gastroenterology Units most aware of the importance of nutritional problems. Better awareness of correct practices for nutritional support should be promoted, encouraging greater use of diagnostic and monitoring techniques and a more discerning choice of the most suitable type of artificial nutrition to be administered in gastroenterology

Tauroursodeoxycholic acid for the treatment of HCV-related chronic hepatitis: a multicenter placebo-controlled study.

BACKGROUND/AIMS: Tauroursodeoxycholic acid is a promising drug for the treatment of chronic cholestatic liver diseases since it has more favourable physicochemical and metabolic properties than ursodeoxycholic acid. Tauroursodeoxycholic acid may be of benefit also for necroinflammatory liver disease, especially for HCV-related chronic hepatitis in which bile duct damage and some degree of cholestasis are frequently seen at histology. METHODOLOGY: One hundred and fifty patients with chronic hepatitis were randomly assigned to receive tauroursodeoxycholic acid at daily doses of 500 mg or 750 mg, or a placebo for 6 months. RESULTS: A consistent decrease in aminotransferase serum levels was observed in patients treated with tauroursodeoxycholic acid compared with placebo (p<0.001) and a progressive improvement with time was also found (p<0.05; linear time effect). CONCLUSIONS: Tauroursodeoxycholic acid improves the biochemical expression of chronic hepatitis. Long-term studies with clinically relevant end-points are warranted.

Molecular alteration of gastric carcinoma.

Gastric cancer is constituted by two histomorphological entities ''intestinal'' and ''diffuse'' that differ in epidemiology, pathogenesis, clinical outcome and genetic profile. Two distinct molecular pathways of genomic destabilization have been identified in gastric carcinogenesis: the microsatellite mutator phenotype (MMP) and a phenotype associated with chromosomal and intrachromosomal instability (CIN). The microsatellite mutator phenotype is caused by mismatch repair (MMR) deficiency and is associated with mutational inactivation; this condition is identified as microsatellite instability (MIN). CIN is characterized by chromosomal rearrangements and losses or gains of chromosomes, which in turn can induce oncogene activation and/or tumour-suppressor-gene inactivation. Mounting evidence suggests that MMP alterations, DNA aneuploidy and expression of the products of cancer-related genes are early markers of cell transformation, and may serve to identify the genetic pathway of gastric carcinoma. However, the lack of a clear genetic basis lends weight to the notion that gastric cancer may be affected by exposure to environmental factors. Helicobacter pylori is one of the most frequent infections worldwide and is the most important environmental risk factor associated with sporadic gastric cancer. Exposure of gastric epithelial cells to H. pylori results in the generation of reactive oxygen species and an increased level of inducible nitric oxide synthase that in turn may cause genetic alterations leading to cancer in a subset of subjects. In conclusion gastric cancer is the result of an interplay between genetic and environmental factors. The new technologies for the molecular analysis will be a useful tool to understand the individual's risk and settle novel biological therapeutic strategies.

[The epidemiology of cholestasis in hepatopathies]. / Epidemiologia della colestasi nelle epatopatie.

The prevalence of intrahepatic cholestasis in chronic liver disease is still undefined. In this study we evaluated the prevalence and the clinical features of the cholestasis syndrome in 3210 liver disease patients from south Italy, hospitalized in the last 7 years in the Liver Unit of the Medical School of University of Naples. An increase in serum alkaline phosphatase, with or without an increase in serum GGT, was found in 556 subjects (17% of the cases), 64% of whom had also an increase in serum bilirubin. Seventy per cent of cholestatic patients were affected by chronic hepatitis with or without cirrhosis, while 6% were affected by primary biliary cirrhosis or sclerosing cholangitis. A comparison of these results with a multicenter Italy/London study revealed that cholestasis was less frequent in South Italy (7% of chronic hepatitis and 19% of cirrhosis) than in the general survey from Italy (15% and 41%) and from England (30% and 48%). The different etiology and dietary and environmental factors in the different regions compared may account for these discrepancies.

Simulations of dredged sediment spreading on a Posidonia oceanica meadow off the Ligurian coast, Northwestern Mediterranean.

The sandy deposits from dredging can have negative effects on the environment such as increase in suspended solids in the water column and their consequent transport. An experimental study was conducted to characterize water masses, dynamics, and sedimentation rates on the Ligurian continental shelf (Italy), where both a sand deposit, that could be used for beach nourishment, and a nearby Posidonia oceanica meadow coexist. The environmental plan provides a mathematical simulation of the sediment-dispersion to evaluate the possible impact on the meadow. It has been calculated that the dredging could double the concentration of suspended particles, but its scheduling will preclude a sediment accumulation. All the information obtained from this work will be used to study the environmental feasibility of the sand deposit exploitation and as starting point for drawing up the monitoring plan in case of dredging.