Camillo Del Vecchio Blanco

Helicobacter pylori Up-regulates Cyclooxygenase-2 mRNA Expression and Prostaglandin E2 Synthesis in MKN 28 Gastric Mucosal Cells in Vitro

Helicobacter pylori has been suggested to play a role in the development of gastric carcinoma in humans. Also, mounting evidence indicates that cyclooxygenase-2 overexpression is associated with gastrointestinal carcinogenesis. We studied the effect of H. pylori on the expression and activity of cyclooxygenase-1 and cyclooxygenase-2 in MKN 28 gastric mucosal cells. H. pylori did not affect cyclooxygenase-1 expression, whereas cyclooxygenase-2 mRNA levels increased by 5-fold at 24 h after incubation of MKN 28 cells with broth culture filtrates or bacterial suspensions from wild-type H. pyloristrain. Also, H. pylori caused a 3-fold increase in the release of prostaglandin E2, the main product of cyclooxygenase activity. This effect was specifically related toH. pylori because it was not observed withEscherichia coli and was independent of VacA, CagA, or ammonia. H. pylori isogenic mutants specifically lackingpicA or picB, which are responsible for cytokine production by gastric cells, were less effective in the up-regulation of cyclooxygenase-2 mRNA expression and in the stimulation of prostaglandin E2 release compared with the parental wild-type strain. This study suggests that development of gastric carcinoma associated with H. pylori infection may depend on the activation of cyclooxygenase-2-related events.

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation.

Gut-liver axis: a new point of attack to treat chronic liver damage?

excision without further waiting for repeat endoscopy and “blind” tissue biopsy. Figure 1 shows a midtransverse lesion (Japanese Research Society Classification Isp) that was treated with EMR (8) after exclusion of a submucosally invasive type V pit pattern within an area of central depression. HRMC postresection demonstrated residual tissue with a type IIIs pit pattern. The resection margin was subsequently extended using a second lateralized submucosal saline “lift.” Resection margins at this point were then reassessed after a second dye spray with 0.5% indigo carmine. After this, a mucosal toilet with normal saline was applied with subsequent mucolysis using 5 mL of acetylcystine (2 mg/mL) and localized application of crystal violet (0.05%) using a steel tipped catheter (Olympus 111019, Tokyo, Japan) around the remaining circumferential border. Type I pit was evident, indicative of complete resection margins. Histological examination confirmed the complete excision of colonic adenocarcinoma, with clear vertical and horizontal margins. Further studies assessing the efficacy of this technique in a large prospective cohort are required.

Gut microbiota and probiotics in chronic liver diseases

There is a strong relationship between liver and gut: the portal system receives blood from the gut, and intestinal blood content activates liver functions. The liver, in turn, affects intestinal functions through bile secretion into the intestinal lumen. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of complications of liver cirrhosis, such as infections, hepatic encephalopathy, spontaneous bacterial peritonitis, and renal failure. Probiotics have been suggested as a useful integrative treatment of different types of chronic liver damage, for their ability to augment intestinal barrier function and prevent bacterial translocation. This review summarizes the main literature findings about the relationships between gut microbiota and chronic liver disease, both in the pathogenesis and in the treatment by probiotics of the liver damage.

Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1–2 hepatic encephalopathy

In 40 patients with cirrhosis on a dietary protein regimen of 1 g/kg b.w., we determined the effect on chronic hepatic encephalopathy of long-term administration of Enterococcus faecium (SF68) versus lactulose. The patients received one of the two treatments for three periods of 4 weeks, each separated by drug-free 2-week intervals. The efficacy of treatment was assessed by arterial blood ammonia concentration, mental status, number connection (Reitans part A) test and flash-evoked visual potentials. At the end of the third period the reduction in both blood ammonia concentrations and Reitans test times was more enhanced in patients on SF68 than in patients on lactulose. Furthermore, while patients on lactulose tended to return to basal values during drug-free intervals, responders in the SF68 group maintained improvement throughout the study. In conclusion, SF68 is at least as useful as lactulose for the chronic treatment of chronic hepatic encephalopathy; it has no adverse effects, and treatment can be interrupted for 2 weeks without losing the beneficial effects.

The effect of a silybin-vitamin e-phospholipid complex on nonalcoholic fatty liver disease: a pilot study.

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-β, tumor necrosis factor-α, degree of steatosis, and γ-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage.

Direct evidence of oxidative damage in acute and chronic phases of experimental colitis in rats

During inflammatory colitis in man and experimental animals, the production of free radicals increases. This study evaluated the histological pattern and biochemical parameters of oxidative damage during acute and chronic colitis induced by 2,4,-trinitrobenzenesulfonic acid + ethanol in rats. On the samples of scraped mucosa of six groups of rats, one not treated, one killed after 1 hr, and those killed one, two, four, and eight weeks after the induced-damage, we determined the histological and superoxide dismutase activity and the concentration of lipoperoxides, malonyldialdheyde, and reduced glutathione. After 1 hr, the mucosal damage and superoxide dismutase activity were slight; glutathione, lipoperoxides, and malonyldialdheyde were significantly increased. At one week, the histological damage was severe, decreasing progressively, and significantly correlated to superoxide dismutase activity. Lipoperoxides and malonyldialdheyde were high throughout the study. Glutathione was significantly increased at one and two weeks and dramatically decreased thereafter. Therefore, in experimental colitis the cascade of free-radical production induces a constant self-maintaining lipoperoxidation and consumes the cellular antioxidant capability.

Pretreatment antimicrobial susceptibility testing is cost saving in the eradication of Helicobacter pylori

Abstract Background & Aims: The major obstacle to 100% effective eradication of Helicobacter pylori infection is represented by antimicrobial-resistant H. pylori strains. This randomized study was designed to evaluate whether regimens based on pretreatment susceptibility testing were more effective and cost saving compared with standard nonsusceptibility testing-based therapy in the eradication of H. pylori infection. Methods: We studied 150 consecutive H. pylori -infected dyspeptic subjects. Patients were randomly assigned to omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg twice daily for 7 days or to omeprazole 20 mg twice daily and 2 antimicrobials chosen based on susceptibility testing. H. pylori status was reevaluated 12 weeks after the end of treatment by the 13 C-urea breath test. Results: Susceptibility testing-based regimens led to the following results. (1) Eradication rates were 97.3% (95% confidence interval [CI], 91.2%–99.5%) (71 of 73) and 94.6% (95% CI, 87.6%–98.3%) (71 of 75) in the per-protocol and intention-to-treat analysis, respectively. These were significantly higher ( P Conclusions: Pretreatment antimicrobial susceptibility testing is more effective and cost saving and, in health systems that confirm cost advantage, microbial susceptibility testing should be routinely used for eradication of H. pylori infection.

Intestinal permeability in patients with chronic liver diseases: Its relationship with the aetiology and the entity of liver damage

BACKGROUND Alteration in intestinal permeability may be an important factor in the pathogenesis of both the progression of some chronic liver diseases and the onset of some complications in patients with liver cirrhosis. AIMS To investigate the relationships between intestinal permeability, portal hypertension, alcohol use, plasma levels of pro-inflammatory cytokines, and nitric oxide, expressed as s-nitrosothiols, and nitrite levels in patients with various types and degrees of chronic liver diseases. METHODS 134 healthy volunteers and 83 patients with chronic liver damage entered the study. Intestinal permeability was assessed with the lactulose/mannitol test. Plasma levels of tumour necrosis factor-alpha, interleukin-6, and nitrite and total s-nitrosothiols were determined. RESULTS Intestinal permeability was altered in patients with advanced liver disease and impaired in 15-35% of patients without cirrhosis. Independent factors for intestinal permeability alteration were age, portal hypertension, alcohol use, and diabetes. Plasma levels of inflammatory cytokines and nitrosothiols were significantly higher in patients with altered intestinal permeability. CONCLUSIONS An intestinal permeability evaluation in patients with chronic liver diseases might clarify the significance of intestinal permeability in the pathophysiology of both the progression of liver damage, and the occurrence of complications that accompany liver cirrhosis.

Incidence of altered glucose tolerance in liver cirrhosis

Even though the association between liver cirrhosis and glucose tolerance alterations has been well documented, no data are available on the incidence of this association. In this paper we firstly report the results of a 4-year prospective longitudinal study performed on well-compensated cirrhotic patients with a normal glucose tolerance, in order to evaluate the incidence of glucose tolerance alterations with respect to liver efficiency during the time. The incidence of a diabetic response to a standard OGTT was 4.4% after a 1-year and 21.2% after a 4-year follow-up in stable cirrhotics. These figures are significantly higher than in the general population of our country. This large incidence was even significantly higher in cirrhotics with worsening liver efficiency at the end of the study (35.3%, P < 0.0001). Sex, family history of diabetes, alcoholic aetiology of the cirrhosis, and increment of portal hypertension do not seem to have any significant influence on the frequency of altered glucose tolerance. Therefore, we propose that liver cirrhosis and its worsening play a primary role as diabetogenic risk factors.