Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs

Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are mycotoxins produced by common damp indoor Aspergilli series Versicolores. Since both STC and 5-M-STC were found in the dust of indoor occupational and living areas, their occupants may be exposed to these mycotoxins, primarily by inhalation. Thus, STC and 5-M-STC were intratracheally instilled in male Wistar rats using doses (0.3 mg STC/kg of lung weight (l.w.); 3.6 mg 5-M-STC/kg l.w.; toxin combination 0.3 + 3.6 mg/kg l.w.) that corresponded to concentrations detected in the dust of damp indoor areas in order to explore cytotoxicity, vascular permeability, immunomodulation and genotoxicity. Single mycotoxins and their combinations insignificantly altered lactate-dehydrogenase activity, albumin, interleukin-6, tumor necrosis factor-α and chemokine macrophage inflammatory protein-1α concentrations, as measured by ELISA in bronchioalveolar lavage fluid upon 24 h of treatment. In an alkaline comet assay, both mycotoxins provoked a similar intensity of DNA damage in rat lungs, while in a neutral comet assay, only 5-M-STC evoked significant DNA damage. Hence, naturally occurring concentrations of individual STC may induce DNA damage in rat lungs, in which single DNA strand breaks prevail, while 5-M-STC was more responsible for double-strand breaks. In both versions of the comet assay treatment with STC + 5-M-STC, less DNA damage intensity occurred compared to single mycotoxin treatment, suggesting an antagonistic genotoxic action.     

Metal-loaded Zeolite Remediation of Soils Contaminated with Pandrug-resistant Acinetobacter Baumannii

Due to the development of resistance to antimicrobial agents, bacterium Acinetobacter baumannii is nowadays a leading cause of nosocomial outbreaks. Clinically relevant A. baumannii outside hospital settings including natural soils affected by human waste represents a public-health risk for humans and animals. The aim of this study was to investigate the potential of metal-loaded zeolites to eliminate viable A. baumannii from artificially contaminated natural soils. A. baumannii isolate was subjected to the activity of natural zeolitised tuff (NZ) and Cu-modified (CuNZ) or Ag-modified zeolite (AgNZ) in wet, slightly acidic terra rossa and slightly alkaline red palaeosol. A. baumannii survived in terra rossa and red palaeosol supplemented with 1 wt% of NZ for seven days and four months, respectively. The addition of 1 wt% of CuNZ to terra rossa and red palaeosol shortened the survival of A. baumannii to three and 14 days, respectively. The addition of 0.1 wt% of AgNZ to both soils resulted in complete removal of viable A. baumannii within 1 h of contact, while the total native heterotrophic bacterial counts remained high. Since AgNZ is prepared with a simple modification of cost-effective and environmentally friendly natural zeolite, it is a promising material for the remediation of soils contaminated with pandrug-resistant A. baumannii.     

Assessment of DNA damage in nuclear medicine personnel--comparative study with the alkaline comet assay and the chromosome aberration test

Despite much research over the last few decades, there still remains considerable uncertainty as to the genetic impact of ionizing radiation on human populations, particularly at low levels. The aim of the present study was to provide data on the genetic hazards due to occupational exposure of low doses of ionizing radiation in nuclear medicine departments. The assessment of primary DNA damage in peripheral blood leukocytes of medical staff was performed using the alkaline comet assay and the data obtained were compared with the results of conventional cytogenetic biodosimetry using the chromosome aberration (CA) test. Altogether 120 subjects (60 exposed and 60 controls) participated in the study. Statistically significant increases in primary DNA damage and increased frequencies of CAs compared to controls were observed. Within the exposed population, significant inter-individual differences in DNA damage were found, indicating differences in genome sensitivity. Age and gender were not confounding factors, while smoking enhanced the levels of primary DNA damage only in control subjects, as revealed by both biomarkers studied. The present study suggests that genotoxic damage results from exposure to chronic low doses of ionizing radiation in nuclear medicine departments. Therefore, the exposed medical personnel should carefully comply with the radiation protection procedures and should minimize radiation exposure where possible to avoid potential genotoxic effects. The results obtained in this study point to the significance of biological indicators providing information on the actual risk to the radiation exposed individuals. According to our results, the alkaline comet assay and CA test are sensitive biomarkers that can be used as additional complements to physical dosimetry for assessing exposure to radiation in nuclear medicine personnel.     

DNA methylation patterns in luminal breast cancers differ from non-luminal subtypes and can identify relapse risk independent of other clinical variables

The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by performing genome-wide scans of CpG methylation in breast cancer samples with known expression-based subtypes. Unsupervised hierarchical clustering using a set of most varying loci clustered the tumors into a Luminal A majority (82%) cluster, Basal-like/ErbB2+ majority (86%) cluster and a non-specific cluster with samples that were also inconclusive in their expression-based subtype correlations. Contributing methylation loci were both gene associated loci (30%) and non-gene associated (70%), suggesting subtype dependant genome-wide alterations in the methylation landscape. The methylation patterns of significant differentially methylated genes in luminal A tumors are similar to those identified in CD24?+?luminal epithelial cells and the patterns in basal-like tumors similar to CD44?+?breast progenitor cells. CpG islands in the HOXA cluster and other homeobox (IRX2, DLX2, NKX2-2) genes were significantly more methylated in Luminal A tumors. A significant number of genes (2853, p?相似文献   

Mast cell activation by myelin through scavenger receptor

A role for mast cells (MC) in the pathogenesis of multiple sclerosis (MS) has been suggested, based on the analysis of human lesions and on an animal model of the disease (EAE). What role MC play in the development of MS is not well understood. We hypothesized that the link connecting MC with demyelinating diseases may be represented by their interaction with myelin. Here we show that myelin can activate mast cells. This process could be a key event in the mast cell function required for inducing EAE in mice and possibly in MS in man.     

Identification of a Novel Clone,ST736, among Enterococcus faecium Clinical Isolates and Its Association with Daptomycin Nonsusceptibility

Resistance to daptomycin in enterococcal clinical isolates remains rare but is being increasingly reported in the United States and worldwide. There are limited data on the genetic relatedness and microbiological and clinical characteristics of daptomycin-nonsusceptible enterococcal clinical isolates. In this study, we assessed the population genetics of daptomycin-nonsusceptible Enterococcus faecium (DNSE) clinical isolates by multilocus sequence typing (MLST) and whole-genome sequencing analysis. Forty-two nonduplicate DNSE isolates and 43 randomly selected daptomycin-susceptible E. faecium isolates were included in the analysis. All E. faecium isolates were recovered from patients at a tertiary care medical center in suburban New York City from May 2009 through December 2013. The daptomycin MICs of the DNSE isolates ranged from 6 to >256 μg/ml. Three major clones of E. faecium (ST18, ST412, and ST736) were identified among these clinical isolates by MLST and whole-genome sequence-based analysis. A newly recognized clone, ST736, was seen in 32 of 42 (76.2%) DNSE isolates and in only 14 of 43 (32.6%) daptomycin-susceptible E. faecium isolates (P < 0.0001). This report provides evidence of the association between E. faecium clone ST736 and daptomycin nonsusceptibility. The identification and potential spread of this novel E. faecium clone and its association with daptomycin nonsusceptibility constitute a challenge for patient management and infection control at our medical center.     

Evaluation of genome damage and its relation to oxidative stress induced by glyphosate in human lymphocytes in vitro

In the present study we evaluated the genotoxic and oxidative potential of glyphosate on human lymphocytes at concentrations likely to be encountered in residential and occupational exposure. Testing was done with and without metabolic activation (S9). Ferric‐reducing ability of plasma (FRAP), thiobarbituric acid reactive substances (TBARS) and the hOGG1 modified comet assay were used to measure glyphosate's oxidative potential and its impact on DNA. Genotoxicity was evaluated by alkaline comet and analysis of micronuclei and other nuclear instabilities applying centromere probes. The alkaline comet assay showed significantly increased tail length (20.39 μm) and intensity (2.19%) for 580 μg/ml, and increased tail intensity (1.88%) at 92.8 μg/ml, compared to control values of 18.15 μm for tail length and 1.14% for tail intensity. With S9, tail length was significantly increased for all concentrations tested: 3.5, 92.8, and 580 μg/ml. Using the hOGG1 comet assay, a significant increase in tail intensity was observed at 2.91 μg/ml with S9 and 580 μg/ml without S9. Without S9, the frequency of micronuclei, nuclear buds and nucleoplasmic bridges slightly increased at concentrations 3.5 μg/ml and higher. The presence of S9 significantly elevated the frequency of nuclear instabilities only for 580 μg/ml. FRAP values slightly increased only at 580 μg/ml regardless of metabolic activation, while TBARS values increased significantly. Since for any of the assays applied, no clear dose‐dependent effect was observed, it indicates that glyphosate in concentrations relevant to human exposure do not pose significant health risk. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.     

Proliferationshemmung der AKR-Mäuseleukämie in vivo mit Kalbsmilzextrakt (Lymphozytenchalon)

Ohne Zusammenfassung     

Quantitative analysis of gene expression in human articular chondrocytes assigned for autologous implantation

Autologous chondrocyte implantation (ACI) relies on the implantation of in vitro expanded cells. The aim was to study the dedifferentiation of human articular chondrocytes under different cultivating conditions [days 0–10 in the primary culture (P0); passages in a monolayer from P0 to P3; monolayer vs. alginate and monolayer vs. alginate/agarose hydrogels] using real‐time PCR analysis. The relative gene expressions for collagen type I and II, aggrecan and versican were quantified and the corresponding differentiation indexes (Col2/Col1, Agr/Ver) were calculated. The values of both differentiation indexes decreased exponentially with time in the P0 monolayer culture, and continued with a significant decrease over the subsequent monolayer passages. On the contrary, the chondrocytes seeded in either of the hydrogels significantly increased the indexes compared to their parallel monolayer cultures. These results indicate that alginate and alginate/agarose hydrogels offer an appropriate environment for human articular chondrocytes to redifferentiate after being expanded in vitro. Therefore the three‐dimensional (3D) hydrogel chondrocyte cultures present not only surgical, but also biological advantage over the classic suspension–periosteum chondrocyte implantation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:847–853, 2008