Removal of non-steroidal anti-inflammatory drugs from water by zeolite-rich composites: The interference of inorganic anions on the ibuprofen and naproxen adsorption.

Composites of two natural zeolites - clinoptilolite and phillipsite, and cationic surfactants (cetylpyridinium chloride and Arquad® 2HT-75) were tested for the removal of two emerging contaminants - ibuprofen and naproxen. For each zeolite-rich rock, two different modifications of the zeolitic surfaces were prepared (monolayer and bilayer surfactant coverage). The influence of the initial drug concentrations and contact time on adsorption of these drugs was followed in buffer solution. The Langmuir model showed the highest adsorption capacity for the composite characterized by a bilayered surfactant at the clinoptilolite surface: 19.7 mg/g and 16.1 mg/g for ibuprofen and naproxen, respectively. Also, to simulate real systems, drug adsorption isotherms were conducted in natural water (Grindstone creek water - Columbia, Missouri, USA) by using the best performing adsorbent; in this case, a slight decrease of drug adsorption was recorded. Kinetic runs were performed in distilled water as well as in the presence of ions such as sulfates and bicarbonates; also, in this case, the interfering agents defined an adsorption decrease for bilayer composites.

Correction: Effects of dietary aflatoxin B1 on accumulation and performance in matrinxã fish (Brycon cephalus).

[This corrects the article DOI: 10.1371/journal.pone.0201812.].

Assessment of mycotoxin exposure and risk characterization using occurrence data in foods and urinary biomarkers in Brazil.

This study aimed to assess the exposure of Brazilian residents (N = 86) from rural areas to multiple mycotoxins and characterize the associated risk in two sampling periods (SP) (April-May and December/2016). Mycotoxins in food and urine samples were determined by liquid chromatography coupled to tandem mass spectrometry. Mean probable daily intake (PDI) values based on occurrence data in foods in both SP varied from 0.007 to 0.013, 0.069 to 1.002, 0.119 to 0.321 and 0.013-0.156 µg kg-1 body weight (bw) day-1 for aflatoxins (AFs), deoxynivalenol (DON), fumonisins (FBs) and zearalenone (ZEN), respectively. Mean PDI values based on urinary biomarkers were 0.001, 84.914, 0.031, 0.377 and 0.002 µg kg-1 bw day-1 for AFB1, DON, ochratoxin A (OTA), FB1 and ZEN, respectively. Hazard quotient (HQ) calculated using food data revealed a potential health concern for ZEN in 2nd SP. HQ > 1 based on urinary biomarkers were observed for DON in the two SP. Although OTA was not detected in any food sample, the HQ based on urinary OTA levels was >1 in the 1st SP. Margin of exposure values for AF from food and urine data in the 1st SP were below 10,000, indicating potential health risks.

Co-occurrence of mycotoxins in maize food and maize-based feed from small-scale farms in Brazil: a pilot study.

A limited survey was conducted to assess the co-occurrence of aflatoxins (AF) B1, B2, G1, and G2; fumonisins (FB) B1 and B2; ochratoxin A (OTA); zearalenone (ZEN); and deoxynivalenol (DON) in maize food (N = 26) and animal feed (N = 45) collected from 21 small-scale farms from the states of São Paulo (SP) and Santa Catarina (SC), Brazil. Samples evaluated were maize meal and maize flour for human consumption available in the farm households, and maize-based feed intended for broiler chicks, laying hens, and dairy cows. Analyses of mycotoxins were performed by ultra-performance liquid chromatography coupled with tandem mass spectrometry. The median levels of mycotoxins found in maize food were 2.5 µg/kg (total AF), 120 µg/kg (total FB), 13 µg/kg (ZEN), and 57 µg/kg (DON). All values were below the Brazilian tolerance limits, except for total FB in one sample of maize flour. In feed samples, median levels of total AF, total FB, ZEN, and DON were 100 µg/kg, 680 µg/kg, 160 µg/kg, and 200 µg/kg, respectively. The co-occurrence of two or more mycotoxins was confirmed in 35% and 51% of maize food and feed, respectively. Results indicate a low human exposure to mycotoxins in the small-scale farms evaluated and a higher exposure of farm animals to mycotoxins in the feed.

Effects of dietary aflatoxin B1 on accumulation and performance in matrinxã fish (Brycon cephalus).

Aflatoxins (AF) can be cumulative in fish tissues and can influence weight, length, feed intake and survival depending on the species. The aim of this work is to measure performance and aflatoxin levels in tissues of matrinxã (Brycon cephalus) fish chronically exposed to aflatoxin. Aflatoxin was incorporated into fish diets at the following levels: Control Feed + 0 µg AFB1 kg-1; A. Feed + 10 µg AFB1 kg-1; B. Feed + 20 µg AFB1 kg-1; C. Feed + 50 µg AFB1 kg-1. It was used one tank per treatment, each one with 150 juvenile fish, and three replicates within each tank were used for sampling, that was carried out monthly over a period of six months. Aflatoxin was quantified by HPLC in fish liver and muscle after clean up using immunoaffinity columns. Performance was evaluated by using weight, length, consumption and survival rate. Muscle and liver aflatoxin levels were below the limit of detection in all control samples. Aflatoxins B2, G1 and G2 were not detected in any tissues. Traces (values between limits of detection and quantification) of AFB1 were observed in liver tissue in treatment A from day 30 through 90, reaching 0.32 µg AFB1 kg-1 at 150 days of exposure. Treatment B presented traces up to day 60 and had, with a maximum level of 0.39 µg AFB1 kg-1 at 150 days of exposure. Treatment C had aflatoxin residues after day 30, with values ranging from 0.17 to 0.61 µg AFB1 kg-1 during exposure. Muscle samples only had traces of AFB1 in all treatments. Fish was affected by exposure to AFB1 with higher values (P<0.05) for weight and length in treatments A, B and C relative to controls. Therefore, results indicate that matrinxã do not accumulate AFB1 residues in edible tissues, but chronic exposure affects the species.

High and low nightly running behavior associates with nucleus accumbens N-Methyl-d-aspartate receptor (NMDAR) NR1 subunit expression and NMDAR functional differences.

The extent to which N-Methyl-d-aspartate (NMDA) receptors facilitate the motivation to voluntarily wheel-run in rodents has yet to be determined. In so, we utilized female Wistar rats selectively bred to voluntarily run high (HVR) and low (LVR) nightly distances in order to examine if endogenous differences in nucleus accumbens (NAc) NMDA receptor expression and function underlies the propensity for high or low motivation to voluntarily wheel-run. 12-14 week old HVR and LVR females were used to examine: 1.) NAc mRNA and protein expression of NMDA subunits NR1, NR2A and NR2B; 2.) NMDA current responses in isolated medium spiny neurons (MSNs) and 3.) NMDA-evoked dopamine release in an ex vivo preparation of NAc punches. Expectedly, there was a large divergence in nightly running distance and time between HVR and LVR rats. We saw a significantly higher mRNA and protein expression of NR1 in HVR compared to LVR rats, while seeing no difference in the expression of NR2A or NR2B. There was a greater current response to a 500 ms application of 300 µM of NMDA in medium-spiny neurons isolated from the NAc HVR compared to LVR animals. On average, NMDA-evoked punches (50 µM of NMDA for 10 min) taken from HVR rats retained ∼54% of the dopamine content compared to their bilateral non-evoked sides, while evoked punches from LVR animals showed no statistical decrease in dopamine content compared to their non-evoked sides. Collectively, these data suggest a potential link between NAc NR1 subunit expression as well as NMDA function and the predisposition for nightly voluntary running behavior in rats. In light of the epidemic rise in physical inactivity, these findings have the potential to explain a neuro-molecular mechanism that regulates the motivation to be physically active.

Soy Improves Cardiometabolic Health and Cecal Microbiota in Female Low-Fit Rats.

Phytoestrogen-rich soy is known to ameliorate menopause-associated obesity and metabolic dysfunction for reasons that are unclear. The gut microbiota have been linked with the development of obesity and metabolic dysfunction. We aimed to determine the impact of soy on cardiometabolic health, adipose tissue inflammation, and the cecal microbiota in ovariectomized (OVX) rats bred for low-running capacity (LCR), a model that has been previously shown to mimic human menopause compared to sham-operated (SHM) intact control LCR rats. In this study, soy consumption, without affecting energy intake or physical activity, significantly improved insulin sensitivity and body composition of OVX rats bred for low-running capacity. Furthermore, soy significantly improved blood lipid profile, adipose tissue inflammation, and aortic stiffness of LCR rats. Compared to a soy-free control diet, soy significantly shifted the cecal microbial community of LCR rats, resulting in a lower Firmicutes:Bacteroidetes ratio. Correlations among metabolic parameters and cecal bacterial taxa identified in this study suggest that taxa Prevotella, Dorea, and Phascolarctobacterium may be taxa of interest. Our results suggest that dietary soy ameliorates adiposity, insulin sensitivity, adipose tissue inflammation, and arterial stiffness and exerts a beneficial shift in gut microbial communities in a rat model that mimics human menopause.

Determination of fumonisin B1 levels in body fluids and hair from piglets fed fumonisin B1-contaminated diets.

The levels of fumonisin B1 (FB1) residues in plasma, urine, feces and hair from 24 piglets fed FB1-contaminated diets containing 3.1, 6.1 or 9.0 µg FB1.g-1 for 28 days were determined using liquid chromatography coupled to mass spectrometry (LC-MS/MS). The levels of FB1 in plasma, urine, feces and pooled hair (n = 3) samples varied from 0.15 to 1.08 µg.L-1, 16.09-75.01 µg.L-1, 1.87-13.89 µg.g-1 and 2.08-8.09 ng.g-1, respectively. Significant correlations (r = 0.808-0.885; P < 0.001; N = 18) were found between FB1 intake and plasma FB1 on days 7, 14, 21 and 28. However, urinary FB1 correlated with FB1 intake only on days 7 and 14 (r = 0.561-572; P = 0.02; N = 18). A significant correlation (r = 0.509; P = 0.02; N = 24) was also found for the first time between FB1 in hair samples and FB1 intake. Plasma and urinary FB1 are good biomarkers of early exposure of pigs to low dietary FB1 levels, although plasma is recommended to assess prolonged exposure (>14 days). The possibility to evaluate hair as a biomarker of fumonisin exposure was established, although further studies are needed to provide physiologically based toxicokinetics of residual FB1 in the pig hair.

Discriminant Analyses of the Polyphenol Content of American Elderberry Juice from Multiple Environments Provide Genotype Fingerprint.

The cultivation of American elderberry (Sambucus nigra subsp. canadensis) continues to increase as the use of this botanical has expanded. Elderberries contain a variety of polyphenols, including anthocyanins, which have purported health benefits. However, information is lacking regarding the impact of environmental, management, and genotypic factors on the quantity and type of polyphenols and anthocyanins produced. Quantification of 16 polyphenols including eight anthocyanins present in juice from three genotypes of American elderberry grown at two Missouri sites from 2013 to 2014 was performed. Large variances in anthocyanin and other polyphenol content were observed between the different harvest seasons, locations, and genotypes. Although specific phytochemical trends due to those factors were not apparent, a discriminant analysis was able to correctly identify 45 of 48 juice samples by genotype, based on their polyphenol profiles. This type of characterization could be beneficial in elderberry authentication studies and to help develop and document high-quality dietary supplement products with specific phytochemical contents.

Adsorption of the mycotoxin zearalenone by clinoptilolite and phillipsite zeolites treated with cetylpyridinium surfactant.

In this study, organozeolites were prepared by treatment of the natural zeolites (clinoptilolite and phillipsite) with cetylpyridinium chloride (CP) equivalent to 50 and 100% of their external cation exchange capacities (ECEC). Organoclinoptilolites (ZCPs) and organophillipsites (PCPs) were characterized by FTIR spectroscopy, thermal analysis, determination of the point of zero charge and zeta potential. Adsorption of zearalenone (ZEN) by ZCPs and PCPs at pH 3 and 7 was investigated. Results showed that adsorption of ZEN increases with increasing amounts of CP at the zeolitic surfaces for both ZCPs and PCPs but the adsorption mechanism was different. Adsorption of ZEN by ZCPs followed a linear type of isotherm at pH 3 and 7 while ZEN adsorption by PCPs showed non linear (Langmuir and Freundlich) type of isotherm at both pH values. Different interactions between the ZEN molecule (or ion) and ZCPs and PCPs occurred: partition (linear isotherms) and adsorption in addition to partition (non linear isotherms), respectively. For the highest level of organic phase at the zeolitic surfaces, the maximum adsorbed amount of ZEN was 5.73mg/g for organoclinoptilolite and 6.86mg/g for organophillipsite at pH 3. Slightly higher adsorption: 6.98mg/g for organoclinoptilolite and 7.54mg/g for organophillipsite was achieved at pH 7. The results confirmed that CP ions at both zeolitic surfaces are responsible for ZEN adsorption and that organophillipsites are as effective in ZEN adsorption as organoclinoptilolites.

Changes in renal gene expression associated with induced ochratoxicosis in chickens: activation and deactivation of transcripts after varying durations of exposure.

Exposure to ochratoxin A (OTA) can lead to changes in global gene expression. This study investigated the individual expression of genes turned on and off in renal cells of chicks after different durations of exposure to dietary OTA. One hundred and eighty day-old male broiler chicks (Ross 308) were randomly assigned to a 3 × 3 factorial arrangement of treatments (3 levels of OTA: 0, 1 and 2 mg OTA/kg diet and 3 time periods: 7, 14 and 21 d). Birds were allocated to 36 pens (4 replicate pens of 5 birds each per treatment). For RNA-Sequencing analysis (RNA-Seq), kidney samples were collected weekly from 3 controls and 3 chicks fed 1 mg OTA/kg. Birds fed 2 mg OTA/kg diet were not chosen for analysis because their reduced feed intake could affect gene expression. The libraries were constructed by Illumina's TruSeq RNA protocol. NextGENe software was used for alignment and transcript quantification. Reads per kilobase of target per million tiled reads (RPKM) were used in the Binary test analysis (P < 0.05). The highest RPKM values were used as criterion for the selection of the genes described. A total of 27,638,976 50-bp RNA-Seq reads were produced over the 3 time periods. Transcripts (40,782) were assembled de novo and annotated by homology to either G. gallus or H. sapiens. The genes activated at 7 d were IL9 and TULP1, at 14 d was GHSR and at 21 d were GRK6 and GAPDH. Unlike all other genes, LOC396365 was activated during all time periods. In contrast, the genes deactivated at 7 d were SPAG4 and LOC100857131, at 14 d were LOC771469, NKX2-1, NKX2-8, FOXO1, MyHC and CLDN18 and at 21 d was XPC. The B-G gene was turned off at 7 and 21 d. All of these genes were involved in kidney toxicity. Therefore, the turning on and off responses of these genes may contribute to carcinogenic and tumorigenic effects of OTA in birds.

Structure-function analysis of Avian ß-defensin-6 and ß-defensin-12: role of charge and disulfide bridges.

BACKGROUND: Avian beta-defensins (AvBD) are small, cationic, antimicrobial peptides. The potential application of AvBDs as alternatives to antibiotics has been the subject of interest. However, the mechanisms of action remain to be fully understood. The present study characterized the structure-function relationship of AvBD-6 and AvBD-12, two peptides with different net positive charges, similar hydrophobicity and distinct tissue expression profiles. RESULTS: AvBD-6 was more potent than AvBD-12 against E. coli, S. Typhimurium, and S. aureus as well as clinical isolates of extended spectrum beta lactamase (ESBL)-positive E. coli and K. pneumoniae. AvBD-6 was more effective than AvBD-12 in neutralizing LPS and interacting with bacterial genomic DNA. Increasing bacterial concentration from 10(5) CFU/ml to 10(9) CFU/ml abolished AvBDs' antimicrobial activity. Increasing NaCl concentration significantly inhibited AvBDs' antimicrobial activity, but not the LPS-neutralizing function. Both AvBDs were mildly chemotactic for chicken macrophages and strongly chemotactic for CHO-K1 cells expressing chicken chemokine receptor 2 (CCR2). AvBD-12 at higher concentrations also induced chemotactic migration of murine immature dendritic cells (DCs). Disruption of disulfide bridges abolished AvBDs' chemotactic activity. Neither AvBDs was toxic to CHO-K1, macrophages, or DCs. CONCLUSIONS: AvBDs are potent antimicrobial peptides under low-salt conditions, effective LPS-neutralizing agents, and broad-spectrum chemoattractant peptides. Their antimicrobial activity is positively correlated with the peptides' net positive charges, inversely correlated with NaCl concentration and bacterial concentration, and minimally dependent on intramolecular disulfide bridges. In contrast, their chemotactic property requires the presence of intramolecular disulfide bridges. Data from the present study provide a theoretical basis for the design of AvBD-based therapeutic and immunomodulatory agents.

Unveiling the anti-inflammatory activity of Sutherlandia frutescens using murine macrophages.

Sutherlandia frutescens is a botanical widely used in southern Africa for treatment of inflammatory and other conditions. Previously, an ethanolic extract of S. frutescens (SFE) has been shown to inhibit the production of reactive oxygen species (ROS) and nitric oxide (NO) by murine neurons and a microglia cell line (BV-2 cells). In this study we sought to confirm the anti-inflammatory activities of SFE on a widely used murine macrophage cell line (i.e., RAW 264.7 cells) and primary mouse macrophages. Furthermore, experiments were conducted to investigate the anti-inflammatory activity of the flavonol and cycloartanol glycosides found in high quantities in S. frutescens. While the SFE exhibited anti-inflammatory activities upon murine macrophages similar to that reported with the microglia cell line, this effect does not appear to be mediated by sutherlandiosides or sutherlandins. In contrast, chlorophyll in our extracts appeared to be partly responsible for some of the activity observed in our macrophage-dependent screening assay.

Immuno-stimulatory activity of a polysaccharide-enriched fraction of Sutherlandia frutescens occurs by the toll-like receptor-4 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sutherlandia frutescens (L.) R. Br. is an indigenous plant of southern Africa that has been traditionally used for various cancers, infections, and inflammatory conditions. AIM OF THE STUDY: Our aim was to investigate the potential immuno-stimulatory activity of a polysaccharide-enriched fraction (SFPS) from a decoction of S. frutescens. MATERIALS AND METHODS: RAW 264.7 cells (a murine macrophage cell line) were used to determine the activities of SFPS on macrophage function. The production of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines were evaluated in the cells treated with or without SFPS. CLI-095, a toll-like receptor (TLR) 4-specific inhibitor, was used to identify whether or not SFPS exerts its effects through TLR4. An antagonist of endotoxin, polymyxin B, was used to evaluate whether endotoxin present in SFPS contributed to its immune-stimulatory activity. RESULTS: SFPS exhibited potent immune-stimulatory activity by macrophages. The production of ROS, NO, and tumor necrosis factor (TNF-α) were increased upon exposure to SFPS in a dose-dependent manner. All of these activities were completely blocked by co-treatment with CLI-095, but only partially diminished by polymyxin B. CONCLUSION: We demonstrate for the first time potent immune-stimulatory activity in a decoction prepared from S. frutescens. We believe that this immune stimulatory activity is due, in part, to the action of polysaccharides present in the decoction that acts by way of TLR4 receptors and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. These findings provide a plausible mechanism through which we can understand some of the medicinal properties of S. frutescens.

Inhibition of microglial activation by elderberry extracts and its phenolic components.

AIMS: Elderberry (Sambucus spp.) is one of the oldest medicinal plants noted for its cardiovascular, anti-inflammatory, and immune-stimulatory properties. In this study, we investigated the anti-inflammatory and anti-oxidant effects of the American elderberry (Sambucus nigra subsp. canadensis) pomace as well as some of the anthocyanins (cyanidin chloride and cyanidin 3-O-glucoside) and flavonols (quercetin and rutin) in bv-2 mouse microglial cells. MAIN METHODS: The bv-2 cells were pretreated with elderberry pomace (extracted with ethanol or ethyl acetate) or its anthocyanins and flavonols and stimulated by either lipopolysaccharide (LPS) or interferon-γ (IFNγ). Reactive oxygen species (ROS) and nitric oxide (NO) production (indicating oxidative stress and inflammatory response) were measured using the ROS detection reagent DCF-DA and the Griess reaction, respectively. KEY FINDINGS: Analysis of total monomeric anthocyanin (as cyanidin 3-O-glucoside equivalents) indicated five-fold higher amount in the freeze-dried ethanol extract as compared to that of the oven-dried extract; anthocyanin was not detected in the ethyl acetate extracts. Elderberry ethanol extracts (freeze-dried or oven-dried) showed higher anti-oxidant activities and better ability to inhibit LPS or IFNγ-induced NO production as compared with the ethyl acetate extracts. The phenolic compounds strongly inhibited LPS or IFNγ-induced ROS production, but except for quercetin, they were relatively poor in inhibiting NO production. SIGNIFICANCE: These results demonstrated differences in anti-oxidative and anti-inflammatory effects of elderberry extracts depending on solvents used. Results further identified quercetin as the most active component in suppressing oxidative stress and inflammatory responses on microglial cells.

Isolation of Sutherlandioside B from Sutherlandia frutescens by Spiral Countercurrent Chromatography.

The introduction of spiral countercurrent chromatography in the last few years using new separation columns such as the spiral tubing support rotor has enabled the application of more polar volatile solvent systems for natural products separation. This method can be applied to water soluble compounds and their metabolites. We have used spiral countercurrent chromatography with the spiral tubing support rotor to fractionate n-butanol extracts of an African plant Sutherlandia frutescens and have determined conditions by which the predominant cycloartane glycoside (sutherlandioside B) can be purified in good yield. A solvent system of ethyl acetate, methanol, and water was modified by adding n-butanol to separate sutherlandioside B from other compounds. With the optimal amount of n-butanol in the two-phase solvent system with the lower aqueous phase mobile, the target compound was eluted well separated from the other components. The purity of sutherlandioside B was determined by high performance liquid chromatography/mass spectrometry analysis and the yield compares favorably with the content in bulk material.

Sutherlandia frutescens ethanol extracts inhibit oxidative stress and inflammatory responses in neurons and microglial cells.

Sutherlandia frutescens (L.) R.Br. (SF) is a medicinal plant indigenous to southern Africa and used in folk and contemporary remedies for stress, chronic diseases, cancer, and HIV/AIDS. While previous studies have focused on physiological effects of SF on cellular and systemic abnormalities associated with these diseases, little is known about its effects in the brain and immune cells in the central nervous system. Results of this study indicate that ethanol extracts of SF (SF-E) suppress NMDA-induced reactive oxygen species (ROS) production in neurons, and LPS- and IFNγ-induced ROS and nitric oxide (NO) production in microglial cells. SF-E's action on microglial cells appears to be mediated through inhibition of the IFNγ-induced p-ERK1/2 signaling pathway which is central to regulating a number of intracellular metabolic processes including enhancing STAT1α phosphorylation and filopodia formation. The involvement of SF in these pathways suggests the potential for novel therapeutics for stress and prevention, and/or treatment of HIV/AIDS as well as other inflammatory diseases in the brain.

Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour.

We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVR(non-run) and HVR(non-run)), as well as in rats after 6 days of voluntary wheel running (LVR(run) and HVR(run)). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that 'cell cycle'-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9-10 LVR(non-run) rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P < 0.001) and fewer immature (Dcx-positive) neurons (P < 0.001) than their G9-10 HVR counterparts. However, voluntary running wheel access in our G9-10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats.

Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer.

Trans-resveratrol, present in high concentration in the skin of red grapes and red wine, has a dose-dependent antiproliferative effect in vitro, prevents the formation of mammary tumors, and has been touted as a chemopreventive agent. Based upon in vitro studies demonstrating that trans-resveratrol downregulates the expression of 1) DNA methyltransferases and 2) the cancer promoting prostaglandin (PG)E(2), we determined if trans-resveratrol had a dose-related effect on DNA methylation and prostaglandin expression in humans. Thirty-nine adult women at increased breast cancer risk were randomized in double-blind fashion to placebo, 5 or 50 mg trans-resveratrol twice daily for 12 wk. Methylation assessment of 4 cancer-related genes (p16, RASSF-1α, APC, CCND2) was performed on mammary ductoscopy specimens. The predominant resveratrol species in serum was the glucuronide metabolite. Total trans-resveratrol and glucuronide metabolite serum levels increased after consuming both trans-resveratrol doses (P < .001 for both). RASSF-1α methylation decreased with increasing levels of serum trans-resveratrol (P = .047). The change in RASSF-1α methylation was directly related to the change in PGE(2) (P = .045). This work provides novel insights into the effects of trans-resveratrol on the breast of women at increased breast cancer risk, including a decrease in methylation of the tumor suppressor gene RASSF-1α. Because of the limited sample size, our findings should be validated in a larger study.

Influence of gamma radiation on productivity parameters of chicken fed mycotoxin-contaminated corn.

The aim of this study was to evaluate productivity parameters and carcass yield of broiler chickens fed irradiated corn contaminated with mycotoxins. For this purpose, 180 one-day-old male chicks were divided into nine treatments and fed for 42 days. The results indicated that irradiation of corn with 5 kGy improved the productivity parameters studied. Therefore, gamma radiation may become an alternative for the control of the deleterious effects of mycotoxins on broiler chickens, which cause marked economic losses for rural producers.