Claritromycin resistance and Helicobacter pylori genotypes in Italy

The relationship between H. pylori clarithromycin resistance and genetic pattern distribution has been differently explained from different geographic areas. Therefore, we aimed to assess the clarithromycin resistance rate, to evaluate the bacterial genetic pattern, and to search for a possible association between clarithromycin resistance and cagA or vacA genes. This prospective study enrolled 62 consecutive H. pylori infected patients. The infection was established by histology and rapid urease test. Clarithromycin resistance, cagA and vacA status, including s/m subtypes, were assessed on paraffin-embedded antral biopsy specimens by TaqMan real time polymerase chain reaction (PCR). Primary clarithromycin resistance was detected in 24.1 % of cases. The prevalence of cagA was 69.3 %, and a single vacA mosaicism was observed in 95.1 % cases. In detail, the s1m1 was observed in 23 (38.9 %) patients, the s1m2 in 22 (37.2 %), and the s2m2 in 14 (23.7 %), whereas the s2m1 combination was never found. The prevalence of cagA and the vacA alleles distribution did not significantly differ between susceptible and resistant strains. Primary clarithromycin resistance is high in our area. The s1m1 and s1m2 are the most frequent vacA mosaicisms. There is no a relationship between clarithromycin resistance and bacterial genotypic pattern and/or cagA positivity.     

Apoptosis promoted by up-regulation of TFPT (TCF3 fusion partner) appears p53 independent, cell type restricted and cell density influenced

The TFPT/FB1 gene was identified because of its involvement in childhood pre-B acute lymphoblastic leukaemia (ALL). Although its specific function is still unclear, Tfpt has been implicated in cell proliferation and induction of programmed cell death (PCD). Given the critical role of PCD in leukemogenesis, we have investigated the responsiveness of different cell lines to TFPT over expression and the consequent induction of PCD by proliferation kinetic analysis, immunolocalization and TUNEL assay. We have also tested the involvement of factors implicated in cell cycle progression and apoptosis, i.e. caspases, p53, Cdc2. Our results indicate that over expression of TFPT promotes caspase 9-dependent apoptosis, nevertheless the apoptotic cascade is engaged only in culture conditions sustaining cell proliferation and different cell lines display differential responsiveness to TFPT induced apoptosis Although p53 is a main regulator of apoptosis in mammalian cells, the Tfpt induced apoptosis appears p53-independent. These results are discussed relatively to the role played by TFPT in leukemogenesis.     

Differential role of NADP+ and NADPH in the activity and structure of GDP-D-mannose 4,6-dehydratase from two chlorella viruses

GDP-D-mannose 4,6-dehydratase (GMD) is a key enzyme involved in the synthesis of 6-deoxyhexoses in prokaryotes and eukaryotes. Paramecium bursaria chlorella virus-1 (PBCV-1) encodes a functional GMD, which is unique among characterized GMDs because it also has a strong stereospecific NADPH-dependent reductase activity leading to GDP-D-rhamnose formation (Tonetti, M., Zanardi, D., Gurnon, J., Fruscione, F., Armirotti, A., Damonte, G., Sturla, L., De Flora, A., and Van Etten, J.L. (2003) J. Biol. Chem. 278, 21559-21565). In the present study we characterized a recombinant GMD encoded by another chlorella virus, Acanthocystis turfacea chlorella virus 1 (ATCV-1), demonstrating that it has the expected dehydratase activity. However, it also displayed significant differences when compared with PBCV-1 GMD. In particular, ATCV-1 GMD lacks the reductase activity present in the PBCV-1 enzyme. Using recombinant PBCV-1 and ATCV-1 GMDs, we determined that the enzymatically active proteins contain tightly bound NADPH and that NADPH is essential for maintaining the oligomerization status as well as for the stabilization and function of both enzymes. Phylogenetic analysis indicates that PBCV-1 GMD is the most evolutionary diverged of the GMDs. We conclude that this high degree of divergence was the result of the selection pressures that led to the acquisition of new reductase activity to synthesize GDP-D-rhamnose while maintaining the dehydratase activity in order to continue to synthesize GDP-L-fucose.     

Synergistic anti‐proliferative and pro‐apoptotic activity of combined therapy with bortezomib,a proteasome inhibitor,with anti‐epidermal growth factor receptor (EGFR) drugs in human cancer cells

The article to which this erratum refers was published in J Cell Physiol (2008) 216: 698–707. © 2008 Wiley‐Liss, Inc. DOI: 10.1002/jcp.21444     

Arylamidonaphtalene sulfonate compounds as a novel class of heparanase inhibitors

The search for antimetastatic agents for cancer therapy may involve the ability of new compounds to maintain the tissue extracellular matrix integrity. Among known factors, heparanase, an endoglucuronidase responsible for heparan sulfate cleavage, is a promising target whose inhibition could represent a strong obstacle for metastatic cancerous mechanisms. The antimetastatic activity of some suramin derivatives reported in literature suggests a possible involvement of the heparanase enzyme. To confirm such hypothesis, we have investigated FCE27266, a molecule known for its antiangiogenic and antimetastatic properties. Other new derivatives were also synthesized and investigated. Our findings revealed that FCE27266 as well as some derivatives have a strong heparanase inhibition activity, together with no cytotoxic power. Moreover, a FCE27266 analogue (SST0546NA1; 17a) resulted also positive to lower gene expression of some proangiogenic factors.     

The azidopentacyanoferrate(III) ion as a tecton in constructing heterometallic complexes: Synthesis, crystal structure and magnetic properties of [Mn(valphen)(H2O)2]2[(H2O)(valphen)Mn(μ-CN)Fe(CN)4(N3)]·8H2O

By employing the common precursor Na₃[Fe(CN)₅(NH₃)]·3H₂O in a new synthetic approach, the azidopentacyanoferrate(III) ion has been isolated and structurally characterized as (Ph₄As)₂[Na(H₂O)₄][Fe(CN)₅(N₃)] 1. In order to confirm its building block ability, compound 1 has been reacted with the mononuclear complex [Mn(valphen)(H₂O)₂]ClO₄ (H₂valphen represents the Schiff base resulting from the condensation of o-vanillin with 1,2-phenylenediamine in a 2:1 M ratio) to afford the new Mn^III-Fe^III heterometallic system [Mn(valphen)(H₂O)₂]₂[(H₂O)(valphen)Mn(μ-CN)Fe(CN)₄(N₃)]·8H₂O 2. The crystal structure of compound 2 reveals a supramolecular assembly generated by [(H₂O)(valphen)Mn(μ-CN)Fe(CN)₄(N₃)]²⁻ dianions and discrete [Mn(valphen)(H₂O)₂]⁺ counterions. The dynamic magnetic measurements of compound 2 point to a slow relaxation of the magnetization.     

Higher Prevalence and Abundance of Bdellovibrio bacteriovorus in the Human Gut of Healthy Subjects

Introduction

Members of the human intestinal microbiota are key players in maintaining human health. Alterations in the composition of gut microbial community (dysbiosis) have been linked with important human diseases. Understanding the underlying processes that control community structure, including the bacterial interactions within the microbiota itself, is essential. Bdellovibrio bacteriovorus is a gram-negative bacterium that preys other gram-negative species for survival, acting as a population-balancer. It was found in terrestrial/aquatic ecosystems, and in animal intestines, postulating its presence also in the human gut.

Methods

The present study was aimed to evaluate, by end-point PCR and qPCR, the presence of B. bacteriovorus in intestinal and faecal biopsy specimens from 92 paediatric healthy subjects and patients, suffering from Inflammatory Bowel Diseases (IBD), Celiac disease and Cystic fibrosis (CF).

Results

i) B. bacteriovorus was present and abundant only in healthy individuals, while it was heavily reduced in patients, as in the case of IBD and Celiac, while in CF patients and relative controls we observed comparable results; ii) B. bacteriovorus seemed to be mucosa-associated, because all IBD and Celiac biopsies (and related controls) were treated with mucus-removing agents, leaving only the mucosa-attached microflora; iii) B. bacteriovorus abundance was district-dependent, with a major preponderance in duodenum, and gradually decreasing up to rectum; iv) B. bacteriovorus levels significantly dropped in disease status, in duodenum and ileum.

Conclusions

Results obtained in this study could represent the first step for new therapeutic strategies aimed to restore a balance in the intestinal ecosystem, utilizing Bdellovibrio as a probiotic.