Zearalenone activates pregnane X receptor, constitutive androstane receptor and aryl hydrocarbon receptor and corresponding phase I target genes mRNA in primary cultures of human hepatocytes

The mycotoxin zearalenone (ZEN) is found worldwide as a contaminant in cereals and grains. ZEN subchronic and chronic toxicities are dominated by reproductive disorders in different mammalian species which have made ZEN established mammalian endocrine disrupter. Over the last 30 years of ZEN biotransformation study, the toxin was thought to undergo reductive metabolism only, with the generation in several species of α- and β-isomers of zearalenol. However, recent investigations have noticed that the mycoestrogen is prone to oxidative metabolism leading to hydroxylation of ZEN though the involvement of different cytochromes P450 (CYPs) isoforms. The aim of the present study was to further explore the effect of ZEN on regulation of some CYPs using primary cultures of human hepatocytes. For this aim, using real time RT-PCR, we monitored in a first time, the effect of ZEN on mRNA levels of pregnane X receptor (PXR), constitutive androstane receptor (CAR) and aryl hydrocarbon receptor (AhR), nuclear receptors known to be involved in the regulation of some CYPs. In a second time, we looked for ZEN effect on expression of PXR, CAR and AhR corresponding phase I target genes (CYP3A4, CYP3A5, CYP2B6, CYP2C9, CYP1A1 and CYP1A2). Finally, we realised the luciferase assay in HepG2 treated with the toxin and transiently transfected with p-CYP3A4-Luc in the presence of a hPXR vector or transfected with p-CYPA1-Luc.Our results clearly showed that ZEN activated human PXR, CAR and AhR mRNA levels in addition to some of their phase I target genes mainly CYP3A4, CYP2B6 and CYP1A1 and at lesser extent CYP3A5 and CYP2C9 at ZEN concentrations as low as 0.1 μM.     

Genotoxic damage in hospital workers exposed to ionizing radiation and metabolic gene polymorphisms

Of all workers exposed globally to synthetic sources of radiation, medical personnel represent the largest group, but receive relatively low doses. Accidental or therapeutic acute radiation exposure of humans was observed to induce various forms of cytogenetic damage, including the possibility of increasing the incidence of micronuclei (MN) and chromosomal aberrations (CA). The aim of this study was to assess occupationally induced chromosomal damage in a large population of hospital workers exposed to low doses of ionizing radiation (IR). The cytokinesis-block MN and comet assays were used to examine peripheral blood lymphocytes (PBL) of 31 exposed workers to IR and 33 control subjects corresponding in gender, age, and smoking. Glutathione S-transferases (GSTM1, GSTT1, and GSTP1) are postulated to be involved in the detoxification of endogenous and exogenous genotoxicants. The association between these biomarkers and polymorphic genes of xenobiotic metabolizing enzymes was thus also assessed. MN frequency was significantly higher in the exposed subjects compared controls. Comet assay results showed a significant increase of tail length in workers exposed to IR. Data obtained suggest that GSTM1, GSTT1, and GSTP1 polymorphism do not modify significantly the genotoxic potential of IR. Therefore, the exposed medical personnel need to carefully apply radiation protection procedures and minimize, as low as possible, IR exposure to avoid possible genotoxic effects.     

Validation of the Arabic version of the short Geriatric Depression Scale (GDS-15)

BACKGROUND: This study aimed to examine the validity and reliability of an Arabic version of the 15-item Geriatric Depression Scale (GDS-15). METHODS: 121 community-dwelling older adults and primary care patients aged 60 and above participated in this study. Older adults with dementia, those with thyroid dysfunction, and hearing or speech impairments were excluded. Test-retest reliability was examined by re-administering the translated GDS-15 to a subset of 38 participants at least seven days after the initial interview. RESULTS: The Arabic GDS-15 had good psychometric properties, but the best properties were reported for the 7/8 cutoff. Cronbach's alpha as a measure of internal consistency reliability was high (0.88) and kappa ranged from 0.57 to 0.75. The performance of the GDS-15 was equally good for both community-dwelling older adults and those in primary care settings, and for both forms of the GDS (examiner administered vs. self-administered). CONCLUSION: The Arabic GDS is a useful measure to assess depression among community-dwelling older adults and primary care patients who do not have dementia. Because of the use of formal Arabic, GDS-15 can be widely used with all Arabic-speaking people.     

Capsid Protein-Encoding Genes of Hamster Polyomavirus and Properties of the Viral Capsid

On the basis of its genome organization the hamster polyomavirus (HaPV) is closely related to the murine polyomavirus Py. But HaPV infection, in contrast to Py infection, gives rise to two different tumor types; depending on the hamster strain used for infection, HaPV induces either epitheliomas or lymphomas. Although the HaPV virions were shown to be similar to those of Py and SV40, more precise information about the structure and protein composition of the HaPV capsid was still missing. Here we describe the primary structure of the capsid protein-encoding HaPV genes and the structure and protein composition of the HaPV capsid. Virions isolated from epitheliomas in HaPV-infected hamsters were shown by electron microscopy to be spherical particles with the typical icosahedral structure of polyomaviruses. However, in contrast to the capsids of SV40 and Py, a T = 7 laevo symmetry of HaPV capsids was observed. Separation of HaPV virions in SDS polyacrylamide gels and Western blotting with VP1-specific antisera identified VP1 as the major capsid protein species corresponding in its molecular weight to the predicted value of 41.8 kDa. Because of the presence of two potential translational initiation sites in the VP1 gene, the N-terminal amino acid sequence of virion VP1 was determined and found to start at the second initiation site. The amino acid homologies of HaPV capsid proteins shared with Py varied between 65.5% (VP1), 45.4% (VP3) and 44.6% (VP2), whereas the homologies to the relevant proteins of other polyomaviruses were found to range between 49.6–57.9% for VP1 and 28.9–41% for VP2/VP3.     

Are biopsies during endoscopic ultrasonography necessary for a suspected esophageal leiomyoma? Is laparoscopy always feasible?

The present letter to the editor is related to the work entitled “Large leiomyoma of lower esophagus diagnosed by endoscopic ultrasonography-fine needle aspiration: A case report.” Although endoscopic ultrasonography seems necessary in a suspected leiomyoma of the esophagus, the performance of biopsies via fine needle aspiration is controversial as it increases the risk of complications such as bleeding, infection, and intraoperative perforations. Laparoscopy is the best treatment strategy for small tumors. Laparotomy with tumor enucleation or esophageal resection can be considered in large leiomyomas.