Emilia Carloni

Levofloxacin-based triple therapy vs. quadruple therapy in second-line Helicobacter pylori treatment: a randomized trial

Background : Levofloxacin has been shown to be effective in Helicobacter pylori eradication. Two 10‐day levofloxacin‐based triple therapies were compared with standard 7‐ and 14‐day quadruple regimens in second‐line treatment.

Screening of gene expression profiles in gastric epithelial cells induced by Helicobacter pylori using microarray analysis

H. pylori infection is a major risk factor in gastric cancer development. The availability of cDNA microarrays creates the unprecedented opportunity to examine simultaneously dynamic changes of multiple pathways affected by H. pylori infection.

Treatment of H. pylori Infection: A Review

Helicobacter pylori infection has been indicated as the main pathogenic factor in the development of chronic gastritis, peptic ulcer disease, and gastric malignancies. Although the vast majority of infected subjects do not carry but a mild, asymptomatic gastritis, still there are some cases in which the eradication of the infection appears mandatory. This review addresses current anti-Helicobacter regimens and pharmacological resources, and highlights the pros and cons of each of them, according to the most recent and reliable clinical trials. Also, basic recommendations are given, regarding treatment choice in the event of the failure of a first or second line eradicating strategy, and about the implementation of standard regimens with newer antibacterial devices as probiotics.

Alterations of DNA mismatch repair proteins and microsatellite instability levels in gastric cancer cell lines

Alterations in DNA mismatch repair (MMR) proteins result in microsatellite instability (MSI), increased mutation accumulation at target genes and cancer development. About one-third of gastric cancers display high-level microsatellite instability (MSI-High) and low-level microsatellite instability (MSI-Low) is frequently detected. To determine whether variations in the levels of MMR proteins or mutations in the main DNA MMR genes are associated with MSI-Low and MSI-High in gastric cancer cell lines, the MSI status (MSI-High, MSI-Low or MS-Stable (MSS)) of 14 gastric cancer lines was determined using multiple clone analysis with a panel of five microsatellite markers. Protein levels of hMLH1, hMSH2, hMSH6, hPMS2 and hPMS1 were determined by Western blot. Sequence analysis of hMLH1 and hMSH2 was performed and the methylation status of the hMLH1 promoter was examined. The cell lines SNU1 and SNU638 showed MSI-High, decreased to essentially absent hMLH1 and hPMS2 and reduced hPMS1 and hMSH6 protein levels. The hMLH1 promoter region was hypermethylated in SNU638 cells. The MKN28, MKN87, KATOIII and SNU601 cell lines showed MSI-Low. The MMR protein levels of cells with MSI-Low status was similar to the levels detected in MSS cells. A marked decrease in the expression levels of MutL MMR proteins (hMLH1, hPMS2 and hPMS1) is associated with high levels of MSI mutations in gastric cancer cells. Gastric cancer cell lines with MSI-Low status do not show significant changes in the levels of the main DNA MMR proteins or mutations in the DNA mismatch repair genes hMSH2 and hMLH1. These well-characterized gastric cancer cell lines are a valuable resource to further our understanding of DNA MMR deficiency in cancer development, progression and prognosis.

Anti‐Saccharomyces cerevisiae antibodies and coeliac disease

Anti-Saccharomyces cerevisiae antibodies (ASCA) have been used as serological markers to differentiate between Crohn disease and ulcerative colitis (1). ASCA are clinically useful when associated with ANCA in predicting evolution of indeterminate colitis to Crohn disease or ulcerative colitis and in paediatric inflammatory bowel disease, in which non-invasive diagnostic tests are desirable (2). ASCA positivity is related to Crohn disease and especially with small-bowel involvement (1). ASCA prevalence has therefore been studied in intestinal diseases such as coeliac disease. A recent report showed a high prevalence of ASCA in coeliac disease (3). The aim of our study was to evaluate ASCA prevalence in coeliac patients on a gluten-free diet and in patients with Crohn disease with small-bowel involvement.

δ13CO2 Excretion and Expression of Dyspeptic Symptoms in Patients Evaluated for Helicobacter pylori Infection by [13C] Urea Breath Test

Previous studies showed that either the urease activity possessed by H. pylori and the bacterial load may influence the results of the [13C] urea breath test. However, the correlation between urease activity and dyspepsia is unclear. The aim of our study was to evaluate whether the urease activity of the gastroduodenal tract may influence the severity of dyspeptic symptoms. In all, 2520 dyspeptic patients (1109 men, 1411 women; mean age 47 ± 16 years) without gastroesophageal reflux disease, diabetes, vascular disorders, liver and biliary tract diseases, and tumors of the gastrointestinal tract and with a normal appearing abdominal ultrasonography were enrolled. All these patients underwent a [13C] urea breath test and filled out a questionnaire on dyspeptic symptoms. Subjects were divided in five different groups according to delta over baseline (DOB) values (group 1 < 3.5, group 2 = 3.5–6; group 3 = 6.1–11, group 4 = 11.1–23, group 5 > 23.1). The prevalence and intensity of dyspeptic symptoms were compared among groups. In all, 1688 patients (67%, 928 females and 760 males; mean age 48 ± 15 years) were H. pylori-positive. The chi-squared test and analysis of variance showed increase of frequency and intensity of each dyspeptic symptom according to DOB values. In conclusion, Dyspepsia may parallel gastric urease activity. However, whether higher DOB values are related to higher bacterial load or, alternatively, to the presence of particular H. pylori strains able to produce larger amounts of urease is uncertain.

Gene-expression profile of colorectal adenocarcinoma tissues identified by gene microarray analysis

3651 Background: Several genes are differentially expressed during the multistep process of colorectal carcinogenesis. The human U133A array (Affymetrix) provides a representation of 22.000 genes. Aim of the study was to identify the gene expression of colorectal adenocarcinoma tissues compared to the normal mucosa. METHODS RNA was extracted from 3 samples of moderately differentiated sporadic rectal adenocarcinoma and 3 samples of normal rectal mucosa obtained from the same patients and hybridized against the human U133A array set. Gene expression of tumoral tissues and normal samples was compared; a minimum of 3 times fold differential expression among the same genes in neoplastic and normal samples was considered as significant. Real-time PCR (Roche, Manheim) using the same RNA was also performed on a pool of either up- or down-regulated randomly-selected genes to validate the results. RESULTS Approximately 550 genes showed a significant differential expression in adenocarcinomas compared to normal mucosa. 537 genes were upregulated while 13 genes were downregulated in neoplastic tissues. The up-regulated genes included angiogenic factors (VEGF, PD-ECGF, EGF), markers of proliferation (PCNA), tumoral markers (CEA, ACE), genes involved in chemotherapy activity (Farnesyl-transferase, Topoisomerase-1) and several other genes of unclear function. The down-regulated genes included transcription factors (SPIB), adhesion molecules (Desmin), anti-oxidant (GPX3) and other genes of unclear activity. RT-PCR confirmed the results obtained by the microarray analysis. CONCLUSIONS Colorectal cancer tissues show a different gene expression compared to the normal mucosa. This differential expression includes several known genes involved in cell growth, angiogenesis, transcription and proliferation as well as other genes of unclear activity, which have never previously been associated with cancer. The identification of a panel of genes specifically expressed in neoplastic tisssues may provide a new tool for the molecular diagnosis of colorectal cancer and furnish new molecular targets for innovative therapeutical strategies. No significant financial relationships to disclose.

Helicobacter pylori infection and migraine: Possible role in aetiology and therapeutic implications

AbstractMigraine is the most frequent subtype of primary headache. It affects about 18% of females and 6% of males in the general population. Despite this high frequency the disease is substantially underdiagnosed and undertreated. Several hypotheses have been put forward to explain the pathogenesis of migraine; at present, a derangement of vascular tone is believed to be an essential component for the development of clinical attacks of the disease. Helicobacter pylori infection, the most common cause of gastritis and peptic ulcer, has been recently associated with various primary functional vascular disorders such as primary Raynaud’s phenomenon and recurrent spontaneous abortion. The infection causes a persistent activation of the immune system, which results in local and systemic release of a variety of vasoactive substances. Recent evidence suggest that infection with H. pylori may also be associated with migraine. In patients with migraine who are infected with H. pylori, eradication of the bacterium resulted in the complete disappearance of migraine attacks in 20% of individuals and a significant decrease in intensity, duration and frequency of symptoms in the vast majority of the others. Further studies, however, remain necessary to better determine the pathogenetic mechanisms underlying this association. If confirmed, this could represent a novel diagnostic and therapeutical approach for at least a subgroup of migraineurs.