Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population.

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.

Preliminary survey of the occurrence of mycotoxins in cereals and estimated exposure in a northwestern region of Mexico.

Mycotoxins have several toxicological implications. In the present study, we evaluate the presence of aflatoxin B1 (AFB1), ochratoxin A (OTA), and fumonisin (FB1) in paddy rice, polished rice, and maize from the fields and markets in Nayarit State (Mexico). The results indicated the presence of AFB1 in 21.21% of paddy rice samples and 11.11% of market maize samples. OTA was present in only 3.03% (one sample) of paddy rice samples. FB1 was detected in 87.50% and 88.88% of maize samples from field and market, respectively. The estimated human exposure was calculated for FB1 using the probable daily intake (PDI), which suggested that FB1 could contribute to the development of diseases through the consumption of contaminated maize. Positive samples indicated that some rice and maize samples were not suitable for human consumption. Further efforts are needed to continue monitoring mycotoxins and update national legislation on mycotoxins accordingly.

Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis.

Among the viridans group streptococci, the Streptococcus mitis group is the most common cause of infective endocarditis. These bacteria have a propensity to be ß-lactam resistant, as well as to rapidly develop high-level and durable resistance to daptomycin (DAP). We compared a parental, daptomycin-susceptible (DAPs) S. mitis/S. oralis strain and its daptomycin-resistant (DAPr) variant in a model of experimental endocarditis in terms of (i) their relative fitness in multiple target organs in this model (vegetations, kidneys, spleen) when animals were challenged individually and in a coinfection strategy and (ii) their survivability during therapy with daptomycin-gentamicin (an in vitro combination synergistic against the parental strain). The DAPr variant was initially isolated from the cardiac vegetations of animals with experimental endocarditis caused by the parental DAPs strain following treatment with daptomycin. The parental strain and the DAPr variant were comparably virulent when animals were individually challenged. In contrast, in the coinfection model without daptomycin therapy, at both the 106- and 107-CFU/ml challenge inocula, the parental strain outcompeted the DAPr variant in all target organs, especially the kidneys and spleen. When the animals in the coinfection model of endocarditis were treated with DAP-gentamicin, the DAPs strain was completely eliminated, while the DAPr variant persisted in all target tissues. These data underscore that the acquisition of DAPr in S. mitis/S. oralis does come at an intrinsic fitness cost, although this resistance phenotype is completely protective against therapy with a potentially synergistic DAP regimen.

Constructed wetlands and solar-driven disinfection technologies for sustainable wastewater treatment and reclamation in rural India: SWINGS project.

SWINGS was a cooperation project between the European Union and India, aiming at implementing state of the art low-cost technologies for the treatment and reuse of domestic wastewater in rural areas of India. The largest wastewater treatment plant consists of a high-rate anaerobic system, followed by vertical and horizontal subsurface flow constructed wetlands with a treatment area of around 1,900 m2 and a final step consisting of solar-driven anodic oxidation (AO) and ultraviolet (UV) disinfection units allowing direct reuse of the treated water. The implementation and operation of two pilot plants in north (Aligarh Muslim University, AMU) and central India (Indira Gandhi National Tribal University, IGNTU) are shown in this study. The overall performance of AMU pilot plant during the first 7 months of operation showed organic matter removal efficiencies of 87% total suspended solids, 95% 5-day biological oxygen demand (BOD5) and 90% chemical oxygen demand, while Kjeldahl nitrogen removal reached 89%. The UV disinfection unit produces water for irrigation and toilet flushing with pathogenic indicator bacteria well below WHO guidelines. On the other hand, the AO disinfection unit implemented at IGNTU and operated for almost a year has been shown to produce an effluent of sufficient quality to be reused by the local population for agriculture and irrigation.

Defining daptomycin resistance prevention exposures in vancomycin-resistant Enterococcus faecium and E. faecalis.

Daptomycin is used off-label for enterococcal infections; however, dosing targets for resistance prevention remain undefined. Doses of 4 to 6 mg/kg of body weight/day approved for staphylococci are likely inadequate against enterococci due to reduced susceptibility. We modeled daptomycin regimens in vitro to determine the minimum exposure to prevent daptomycin resistance (Dapr) in enterococci. Daptomycin simulations of 4 to 12 mg/kg/day (maximum concentration of drug in serum [Cmax] of 57.8, 93.9, 123.3, 141.1, and 183.7 mg/liter; half-life [t1/2] of 8 h) were tested against one Enterococcus faecium strain (S447) and one Enterococcus faecalis strain (S613) in a simulated endocardial vegetation pharmacokinetic/pharmacodynamic model over 14 days. Samples were plated on media containing 3× the MIC of daptomycin to detect Dapr. Mutations in genes encoding proteins associated with cell envelope homeostasis (yycFG and liaFSR) and phospholipid metabolism (cardiolipin synthase [cls] and cyclopropane fatty acid synthetase [cfa]) were investigated in Dapr derivatives. Dapr derivatives were assessed for changes in susceptibility, surface charge, membrane depolarization, cell wall thickness (CWT), and growth rate. Strains S447 and S613 developed Dapr after simulations of 4 to 8 mg/kg/day but not 10 to 12 mg/kg/day. MICs for Dapr strains ranged from 8 to 256 mg/liter. Some S613 derivatives developed mutations in liaF or cls. S447 derivatives lacked mutations in these genes. Dapr derivatives from both strains exhibited lowered growth rates, up to a 72% reduction in daptomycin-induced depolarization and up to 6-nm increases in CWT (P<0.01). Peak/MIC and AUC0-24/MIC ratios (AUC0-24 is the area under the concentration-time curve from 0 to 24 h) associated with Dapr prevention were 72.1 and 780 for S447 and 144 and 1561 for S613, respectively. Daptomycin doses of 10 mg/kg/day may be required to prevent Dapr in serious enterococcal infections.

The use of treatment wetlands plants for protein and cellulose valorization in biorefinery platform.

Different wetland plants were evaluated regarding their potential to be used in further green biorefining platforms to produce soluble protein and cellulose-textile fibers. The results show a higher protein content in the plants grown in treatment wetland conditions, compared with the same species grown in natural conditions, and diverse effect on the content of cellulose, hemicellulose, and lignin, depending on the plant species, more than the growing environment. The TW biomass did not represent a risk regarding accumulation of heavy metals, named Pb, Cd, and Cr, since the studied plants did not present it in their tissues, neither in the roots nor in the leaves. The results regarding cellulose quality of the TW plants showed positive results, having values of molar mass distributions and degrees of polymerization that suggest a suitability to be considered for cellulose-fiber textiles studies. This is one of the first approaches, in the TW field, to establish a new criterion for selecting plant species to be planted in the system, aiming at recovering resources and use them as inputs for biorefineries and sustainable biobased products.

Systematic Analysis of Mobile Genetic Elements Mediating ß-Lactamase Gene Amplification in Noncarbapenemase-Producing Carbapenem-Resistant Enterobacterales Bloodstream Infections.

Noncarbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE) are increasingly recognized as important contributors to prevalent carbapenem-resistant Enterobacterales (CRE) infections. However, there is limited understanding of mechanisms underlying non-CP-CRE causing invasive disease. Long- and short-read whole-genome sequencing was used to elucidate carbapenem nonsusceptibility determinants in Enterobacterales bloodstream isolates at MD Anderson Cancer Center in Houston, Texas. We investigated carbapenem nonsusceptible Enterobacterales (CNSE) mechanisms (i.e., isolates with carbapenem intermediate resistance phenotypes or greater) through a combination of phylogenetic analysis, antimicrobial resistance gene detection/copy number quantification, porin assessment, and mobile genetic element (MGE) characterization. Most CNSE isolates sequenced were non-CP-CRE (41/79; 51.9%), whereas 25.3% (20/79) were Enterobacterales with intermediate susceptibility to carbapenems (CIE), and 22.8% (18/79) were carbapenemase-producing Enterobacterales (CPE). Statistically significant copy number variants (CNVs) of extended-spectrum ß-lactamase (ESBL) genes (Wilcoxon Test; P-value < 0.001) were present in both non-CP-CR E. coli (median CNV = 2.6×; n = 17) and K. pneumoniae (median CNV = 3.2×, n = 17). All non-CP-CR E. coli and K. pneumoniae had predicted reduced expression of at least one outer membrane porin gene (i.e., ompC/ompF or ompK36/ompK35). Completely resolved CNSE genomes revealed that IS26 and ISEcp1 structures harboring blaCTX-M variants along with other antimicrobial resistance elements were associated with gene amplification, occurring in mostly IncFIB/IncFII plasmid contexts. MGE-mediated ß-lactamase gene amplifications resulted in either tandem arrays, primarily mediated by IS26 translocatable units, or segmental duplication, typically due to ISEcp1 transposition units. Non-CP-CRE strains were the most common cause of CRE bacteremia with carbapenem nonsusceptibility driven by concurrent porin loss and MGE-mediated amplification of blaCTX-M genes. IMPORTANCE Carbapenem-resistant Enterobacterales (CRE) are considered urgent antimicrobial resistance (AMR) threats. The vast majority of CRE research has focused on carbapenemase-producing Enterobacterales (CPE) even though noncarbapenemase-producing CRE (non-CP-CRE) comprise 50% or more of isolates in some surveillance studies. Thus, carbapenem resistance mechanisms in non-CP-CRE remain poorly characterized. To address this problem, we applied a combination of short- and long-read sequencing technologies to a cohort of CRE bacteremia isolates and used these data to unravel complex mobile genetic element structures mediating ß-lactamase gene amplification. By generating complete genomes of 65 carbapenem nonsusceptible Enterobacterales (CNSE) covering a genetically diverse array of isolates, our findings both generate novel insights into how non-CP-CRE overcome carbapenem treatments and provide researchers scaffolds for characterization of their own non-CP-CRE isolates. Improved recognition of mechanisms driving development of non-CP-CRE could assist with design and implementation of future strategies to mitigate the impact of these increasingly recognized AMR pathogens.

Whole-genome sequencing of Staphylococcus epidermidis bloodstream isolates from a prospective clinical trial reveals that complicated bacteraemia is caused by a limited number of closely related sequence types.

OBJECTIVES: The significance of isolating Staphylococus epidermidis from a blood culture is highly heterogeneous, ranging from contamination to an indication of a serious infection. Herein we sought to determine whether there is a relationship between S. epidermidis genotype and clinical severity of bacteraemia. METHODS: S. epidermidis bacteraemias from a prospective, multicentre trial at 15 centres in the United States and one in Spain were classified as simple (including possible contamination), uncomplicated, and complicated. Whole-genome sequencing (WGS) was performed on 161 S. epidermidis isolates, and clinical outcomes were correlated with genotypic information. RESULTS: A total of 49 S. epidermidis sequence types (STs) were identified. Although strains of all 49 STs were isolated from patients with either simple or uncomplicated infection, all strains causing complicated infections were derived from five STs: ST2, ST5, ST7, ST16, and ST32. ST2 and ST5 isolates were significantly more likely to cause uncomplicated and complicated bloodstream infections compared to simple bacteraemia (odds ratio 2.0, 95%CI 1.1-3.9, p 0.04). By multivariate regression analysis, having an ST2 or ST5 S. epidermidis bacteraemia was an independent predictor of complicated bloodstream infection (odds ratio 3.7, 95%CI 1.2-11.0, p 0.02). ST2/ST5 strains carried larger numbers of antimicrobial resistance determinants compared to non-ST2/ST5 isolates (6.34 ± 1.5 versus 4.4 ± 2.5, p < 0.001). CONCLUSION: S. epidermidis bacteraemia was caused by a genetically heterogeneous group of organisms, but only a limited number of STs-particularly multidrug-resistant ST2 and ST5 strains-caused complicated infections.

PON1 status and homocysteine levels as potential biomarkers for cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death. The mainly risks factors for CVD are diabetes, hypertension and high levels of homocysteine (Hcys), among others. Paraoxonase 1 (PON1) has been proposed as an antiatherogenic target for its ability to hydrolyzing oxi-Low-Density-Lipoproteins (LDL) and Hcys-thiolactone. Thus, the aim of the present study was to evaluate the association of Hcys levels, and the activities and concentration of PON1, as well as vitamin B from the diet with a risk for CVD. METHODS: A case-control study was carry out in patients with cardiovascular diseases (CVD), Arterial hypertension, but not CVD (AH), and in healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, intake of vitamin B, Hcys, serum amyloid A (SAA), PON1 concentration, and PON1 activities (Arylesterase activity (ARE), Lactonase activity (LAC), and CMPA activity (CMPA)) were evaluated. RESULTS: The CVD group had the highest concentration of Hcys and SAA than in the AH and control groups (p < 0.01). ARE, LAC, and CMPA activities and PON1 concentration were lowest in the CVD group. A positive-independent association between Hcys levels and CVD was found (OR = 2.09; 95% CI: 1.69-2.56) and this increase when it was adjusted by age, BMI, ApoA1, vitamin B intake, SAA, and PON1 (OR = 14.41; 95% CI: 1.75-118.71). LAC and CMPA, as well as PON1 concentration, were inversely associated with CVD. CONCLUSION: LAC activity, PON1 concentration, and Hcys levels might be good biomarkers for CVD and their association could be modified by the intake of vitamin B.

PON1 lactonase activity and its association with cardiovascular disease.

BACKGROUND: Paraoxonase 1 (PON1) is important in the development of atherosclerosis, and it has become the subject of intensive research. Our aim was to evaluate the association of serum PON1 activity and polymorphisms with cardiovascular disease (CVD) using four different substrates. MATERIALS AND METHODS: Activity of PON1-related to arylesterase (AREase and 4-CMPAse), paraoxonase (PONase), and lactonase (LACase), and polymorphisms (A-162G, T-108C, L55M, and Q192R) were evaluated in subjects with CVD, cardiovascular risk factor (CFR), and controls. An ordered logistic-regression analysis of PON1 phenotypes was performed in the CVD group with respect to the control group. RESULTS AND CONCLUSIONS: Logistic-regression analysis showed that CC-108 genotype was associated with CRF and CVD. The CVD group had the lowest activities of PON1. The LACase might be a better biomarker for CVD (OR, 0.52; 95% CI, 0.44-0.61) followed by CMPAse (OR, 0.82; 95% CI, 0.77-0.86), AREase (OR, 0.98; 95% CI, 0.97-0.99) and PONase (OR, 0.99, 95% CI, 0.99-0.99). Logistic regression of PON1 phenotypes by haplotypes showed that LACase activity was not influenced by the polymorphisms and that it could be a new potential biomarker in the development of CVD. Larger scale longitudinal studies are required.

Nosocomial outbreak of Enteroccocus gallinarum: untaming of rare species of enterococci.

An unusual increase in infections caused by vancomycin-resistant Enterococcus gallinarum (VREG) was identified in May 2004, in a Colombian tertiary care teaching hospital. A case-control study was subsequently designed to identify risk factors associated with the development of infections due to these organisms. All VREG isolates were subjected to antimicrobial susceptibility testing, vancomycin resistance gene detection and pulsed-field gel electrophoresis (PFGE) typing. Additionally, the presence of genes associated with an acquired pathogenicity island of E. faecalis and a hyl-like gene of E. faecium was assessed by hybridisation assays. Eleven cases of VREG were identified between May through June 2004. VREG was isolated from blood (N=4), surgical secretions (N=4), paranasal sinus secretion (N=1), lung abscess (N=1) and urine (N=1). Infections with VREG were associated with mucositis, hospitalisation in the haematology ward and surgical unit, length of hospital stay prior to culture and invasive procedures within 30 days prior to the culture. Logistic regression found that female sex and hospitalisation in the surgical unit were independent factors for VREG infection. All isolates were identified as E. gallinarum, harboured the vanC1 gene and exhibited indistinguishable restriction patterns by PFGE. Virulence-associated genes were not detected. This is the first documented hospital-wide outbreak of VREG and highlights the fact that uncommon species of enterococci are capable of nosocomial dissemination.

Twenty years experience with constructed wetland systems in Denmark--what did we learn?

Full scale constructed wetland systems for wastewater treatment have been in operation in Denmark since 1983, mainly for the treatment of domestic sewage from small villages. The systems are constructed as soil-based horizontal subsurface flow systems but, because of low soil hydraulic conductivity, surface runoff is evident in most of the systems. Two decades of experience show that soil-based systems are generally efficient in removing suspended solids and BOD, but the removal of nitrogen and phosphorus is lower (typically 30-50%) and the systems do not nitrify ammonium. Contrary to earlier claims, the reeds do not increase the hydraulic conductivity of cohesive soils as much as necessary to secure sub-surface flow. Operation needs of soil-based reed beds are low and normally restricted to emptying of the sedimentation tank, cleaning of the distribution system and mowing of the grass around the system. The dead plant material and accumulated litter on the surface of the systems improve performance after the initial years. A significant number of systems have been shut down or extended with other technologies in order to meet new effluent standards, particularly demands for nitrification. New constructed wetland systems are either compact vertical flow systems which provide good nitrification, willow systems with no discharge or restored wetland systems for nitrate removal. If efficient removal of phosphorus is required, this is achieved by chemical precipitation in the sedimentation tank.

Hydrolytic anaerobic reactor and aerated constructed wetland systems for municipal wastewater treatment - HIGHWET project.

The HIGHWET project combines the hydrolytic up-flow sludge bed (HUSB) anaerobic digester and constructed wetlands (CWs) with forced aeration for decreasing the footprint and improving effluent quality. The HIGHWET plant in A Coruña (NW of Spain) treating municipal wastewater consists of a HUSB and four parallel subsurface horizontal flow (HF) CWs. HF1, HF2 and HF3 units are fitted with forced aeration, while the control HF4 is not aerated. All the HF units are provided with effluent recirculation, but different heights of gravel bed (0.8 m in HF1 and HF2, and 0.5 m in HF3 and HF4) are implemented. Besides, a tobermorite-enriched material was added in the HF2 unit in order to improve phosphorus removal. The HUSB 76-89% of total suspended solids (TSS) and about 40% of chemical oxygen demand (COD) and biological oxygen demand (BOD). Aerated HF units reached above 96% of TSS, COD and BOD at a surface loading rate of 29-47 g BOD5/m2·d. An aeration regime ranging from 5 h on/3 h off to 3 h on/5 h off was found to be adequate to optimize nitrogen removal, which ranged from 53% to 81%. Average removal rates of 3.4 ± 0.4 g total nitrogen (TN)/m2·d and 12.8 ± 3.7 g TN/m3·d were found in the aerated units, being 5.5 and 4.1 times higher than those of the non-aerated system. The tobermorite-enriched HF2 unit showed a distinct higher phosphate (60-67%) and total phosphorus (54%) removal.

Transcriptional regulation of human Paraoxonase 1 by nuclear receptors.

Paraoxonase 1 (PON1) is a calcium-dependent lactonase synthesized primarily in the liver and secreted into the plasma, where it is associates with high density lipoproteins (HDL). PON1 acts as antioxidant preventing low-density lipoprotein (LDL) oxidation, a process considered critical in the initiation and progression of atherosclerosis. Additionally, PON1 hydrolyzes and detoxifies some toxic metabolites of organophosphorus compounds (OPs). Thus, PON1 activity and expression levels are important for determining susceptibility to OPs intoxication and risk of developing diseases related to inflammation and oxidative stress. Increasing evidence has demonstrated the modulation of PON1 expression by many factors is due to interaction with nuclear receptors (NRs). Here, we briefly review the studies in this area and discuss the role of nuclear receptors in the regulation of PON1 expression, as well as how understanding these mechanisms may allow us to manipulate PON1 levels to improve drug efficacy and treat disease.

[Overview of head injury]. / Revisión del traumatismo craneoencefálico.

A systematic revision of the main practical aspects related with the head injury management has been made in this article on the basis of relevant literature. The paper has been developed in different sections consisting of epidemiological factors, prognosis and classification, neuropathology and pathophysiology, clinical evaluation and treatment. According to clinical guidelines, the connections between the pathophysiological features with higher evidence degree and the schemes of therapeutic approaches have been emphasized.

Danish guidelines for small-scale constructed wetland systems for onsite treatment of domestic sewage.

The Danish Ministry of Environment and Energy has passed new legislation that requires the wastewater from single houses and dwellings in rural areas to be treated adequately before discharge into the aquatic environment. Therefore official guidelines for a number of onsite treatment solutions have been produced. These include guidelines for soakaways, biological sand filters, technical systems as well as different types of constructed wetland systems. This paper summarises briefly the guidelines for horizontal flow constructed wetlands, vertical flow constructed wetlands, and willow systems with no outflow and with soil infiltration. There is still a lack of a compact onsite solution that will fulfil the treatment classes demanding 90% removal of phosphorus. Therefore work is presently being carried out to identify simpler and robust P-removal solutions.

Phosphorus removal in constructed wetlands: can suitable alternative media be identified?

Removal of phosphorous in constructed wetlands is limited by the capacity of the media to adsorb, bind or precipitate the incoming P. To enhance P removal and the life span of constructed wetlands the approach might be to use natural sands rich in calcium or iron, to use an alternative 'artificial' medium with high P-binding capacity, or to establish external P-binding filters after the wetland. Our studies focused on the evaluation of calcium-rich materials potentially useful as P-binding media. The materials tested included calcite products, natural sands and seashells. Tests included assessment of physical and chemical properties of the materials, extractions in P-spiked water at different P concentrations to determine P-binding equilibrium isotherms, and column experiments. In addition, full-scale tests were performed with calcite in an external filter. The result showed that equilibrium isotherm is an indicator of the potential P-sorption capacity of the media, although the value is of limited application for the determination of the binding capacity in full-scale systems. The columns showed that the materials do bind phosphorus. However, the binding capacities are still insufficient for the establishment of external P-removal filter; the volumes of the filters would be too large to be of practical use.

Modulation of the xenobiotic transformation system and inflammatory response by ochratoxin A exposure using a co-culture system of Caco-2 and HepG2 cells.

Cytotoxicity of ochratoxin A (OTA) was evaluated using the MTS assay, and membrane integrity was measured using transepithelial electrical resistance (TEER). A transwell system was used to investigate the effect of OTA on the expression of the CYP450 (1A1, 2A6, 2B6, 3A4 and 3A5), NAT2, COX-2, LOX-5, and MRP2 genes in Caco-2 and HepG2 cells. TEER decreased by a mean of 63.2% after 24 h in Caco-2 differentiated cells without inducing cell detachment; revealing damage to the intestinal epithelial cell tight junction proteins and an increase in cell permeability. Gene expression analysis showed that modulation of gene expression by OTA was higher in Caco-2 cells than in HepG2 cells, and generally, the duration of exposure to OTA had a more significant effect than the OTA dose. A general OTA down-regulation effect was observed in Caco-2 cells, in contrast with the down- and up-regulation observed in HepG2 cells. In Caco-2 cells, CYP1A1 was the gene with the highest regulation, followed by CYP3A4 and CYP3A5. Conversely, in HepG2 cells, CYP2B6 was highly regulated at 3 and 12 h compared to the other cytochromes; CYP1A1 was slightly modulated during the first 12 h, but an overexpression was observed at 24 h. Our data support the involvement of the COX-2 and 5-LOX genes in liver metabolism of OTA. On the basis of the gene expression analysis, the results suggest a possible impairment in OTA secretion at the intestinal and hepatic level due to MRP2 repression. In addition, we provide evidence of the effect of OTA on NAT2 gene expression, which had not been reported before.

Cytotoxicity of the mycotoxins deoxynivalenol and ochratoxin A on Caco-2 cell line in presence of resveratrol.

Exposure to mycotoxins through dietary food intake involves a highly complex scenario where co-contamination of different mycotoxins has been frequently demonstrated. On the other hand, the effect of the interaction of mycotoxins with other generally considered beneficial food components, as the antioxidants, has been scarcely studied. The main goal of the present work was to assess the cytotoxic effects on Caco-2 cells of the mycotoxins deoxynivalenol (DON) and ochratoxin A (OTA), alone or combined, and to explore potential protective effects of resveratrol (RES), an antioxidant frequently found in wine. In parallel, reactive oxygen species (ROS) production has also been studied as a first approach to understand the underlying mechanism of cytotoxicity. Results indicate a higher toxic effect of the mycotoxins when they are co-exposed. This increase in cytotoxicity was not accompanied by an increase in ROS production. The co-exposure of OTA or DON with RES did not result in a decrease in cytotoxicity; on the contrary, it resulted in increased cytotoxicity not associated with an increase in ROS production.