Determining mycotoxins and mycotoxigenic fungi in food and feed:Developing biomarkers of human exposure to mycotoxins

Exposure assessment is a critical part of epidemiological studies into the effect of mycotoxins on human health. Whilst exposure assessment can be made by estimating the quantity of ingested toxins from food analysis and questionnaire data, the use of biological markers (biomarkers) of exposure can provide a more accurate measure of individual level of exposure in reflecting the internal dose. Biomarkers of exposure can include the excreted toxin or its metabolites, as well as the products of interaction between the toxin and macromolecules such as protein and DNA. Samples in which biomarkers may be analysed include urine, blood, other body fluids and tissues, with urine and blood being the most accessible for human studies. Here we describe the development of biomarkers of exposure for the assessment of three important mycotoxins; aflatoxin, fumonisin and deoxynivalenol. A number of different biomarkers and methods have been developed that can be applied to human population studies, and these approaches are reviewed in the context of their application to molecular epidemiology research.

Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids

As survival rates of preterm newborns improve as a result of better medical management, these children increasingly show impaired cognition. These adverse cognitive outcomes are associated with decreases in the volume of the cerebellum. Because animals exhibit reduced preterm cerebellar growth after perinatal exposure to glucocorticoids, we sought to determine whether glucocorticoid exposure and other modifiable factors increased the risk for these adverse outcomes in human neonates. We studied 172 preterm neonatal infants from two medical centers, the University of British Columbia and the University of California, San Francisco, by performing serial magnetic resonance imaging examinations near birth and again near term-equivalent age. After we adjusted for associated clinical factors, antenatal betamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone was associated with impaired cerebellar, but not cerebral, growth. Alterations in treatment after preterm birth, particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth.

Prenatal alcohol exposure alters biobehavioral reactivity to pain in newborns

To examine biobehavioral responses to an acute pain event in a Cape Town, South Africa, cohort consisting of 28 Cape Colored (mixed ancestry) newborns (n = 14) heavily exposed to alcohol during pregnancy (exposed), and born to abstainers (n = 14) or light (<or = 0.5 oz absolute alcohol/d) drinkers (controls).

Hypothalamic-pituitary-adrenal (HPA) axis function in 3-month old infants with prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure

Prenatal exposure to stress and selective serotonin reuptake inhibitors (SSRIs) alter hypothalamic-pituitary-adrenal (HPA) stress reactivity in offspring, however, the effects of combined exposure to HPA activity in human infants is unknown.

Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure

In this prospective study, we examined biobehavioral responses to acute procedural pain at 2 months of age in infants with prenatal and postnatal selective serotonin reuptake inhibitor (SSRI) medication exposure. Based on previous findings showing reduced pain responses in newborns after prenatal exposure, we hypothesized that altered pain reactivity would also be found at 2 months of age.

Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU

Data from animal models indicate that neonatal stress or pain can permanently alter subsequent behavioral and/or physiological reactivity to stressors. However, cumulative effects of pain related to acute procedures in the neonatal intensive care unit (NICU) on later stress and/or pain reactivity has received limited attention. The objective of this study is to examine relationships between prior neonatal pain exposure (number of skin breaking procedures), and subsequent stress and pain reactivity in preterm infants in the NICU. Eighty-seven preterm infants were studied at 32 (+/-1 week) postconceptional age (PCA). Infants who received analgesia or sedation in the 72 h prior to each study, or any postnatal dexamethasone, were excluded. Outcomes were infant responses to two different stressors studied on separate days in a repeated measures randomized crossover design: (1) plasma cortisol to stress of a fixed series of nursing procedures; (2) behavioral (Neonatal Facial Coding System; NFCS) and cardiac reactivity to pain of blood collection. Among infants born

Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses

In animal models, variations in early maternal care are associated with differences in hypothalamic-pituitary-adrenal(HPA) stress response in the offspring, mediated via changes in the epigenetic regulation of glucocorticoid receptor (GR) gene (Nr3c1) expression.

Arsenic in groundwater and its influence on exposure risks through traditionally cooked rice in Prey Vêng Province, Cambodia

Arsenic (As) contamination of communal tubewells in Prey Vêng, Cambodia, has been observed since 2000. Many of these wells exceed the WHO As in drinking water standard of 10 µg/L by a factor of 100. The aim of this study was to assess how cooking water source impacts dietary As intake in a rural community in Prey Vêng. This aim was fulfilled by (1) using geostatistical analysis techniques to examine the extent of As contaminated groundwater in Prey Vêng and identify a suitable study site, (2) conducting an on-site study in two villages to measure As content in cooked rice prepared with water collected from tubewells and locally harvested rainwater, and (3) determining the dietary intake of As from consuming this rice. Geostatistical analysis indicated that high risk tubewells (>50 µg As/L) are concentrated along the Mekong River's east bank. Participants using high risk tubewells are consuming up to 24 times more inorganic As daily than recommended by the previous FAO/WHO provisional tolerable daily intake value (2.1 µg/kgBW/day). However, As content in rice cooked in rainwater was significantly reduced, therefore, it is considered to be a safer and more sustainable option for this region.

CUE-EXPOSURE TO ALCOHOL-ASSOCIATED STIMULI REDUCES AUTONOMIC REACTIVITY, BUT NOT CRAVING AND ANXIETY, IN DEPENDENT DRINKERS

A controlled trial was conducted of cue-exposure with dependent drinkers in treatment. All subjects were engaged in an insight-orientated therapy programme, and responses to an alcohol-associated, compared with a neutral, stimulus were assessed at the beginning and end of treatment. Compared with a control group, which did not receive intervening cue-exposure sessions, subjects who received such interventions manifested reductions in heart rate, salivation and arousal responses to the alcohol-associated, compared with the neutral, stimulus. They did not, however, show similar reductions in subjective estimates of craving and anxiety. These results and the desynchrony in reductions in cue-reactivity across response domains are discussed in terms of their implications for cue-exposure in treatment and recent theoretical conceptualizations of the relationship between autonomic reactivity, craving and drinking behaviour.

Digital Exposure of English Place-names (DEEP)

Place-names are a fundamental concept in all academic collections: everything happens somewhere. Contemporary place-names are comprehensively represented in digital gazetteer and geospatial web services such as GeoNames. However, despite millions of pounds of investment by JISC and other agencies in historical online resources in recent years, there is currently no equivalent for historic place-names. This project will digitize the entire 86 volume corpus of the Survey of English Place-Names (SEPN), the ultimate authority on historic place-names in England, and make its 4 million forms available.

Lymphocyte subsets in conjunctival mucosa-associated-lymphoid-tissue after exposure to retinal-S-antigen

Purpose: To evaluate the immune cell subsets in conjunctival mucosa-associated-lymphoid-tissue (C-MALT) following challenge with antigen. Methods: Ten adult female Lewis rats were studied. Five rats received one drop (5 µL) of retinal S-antigen (500 µg/mL in phosphate buffered saline, PBS) instilled into the lower fornix twice daily for 10 consecutive days. Five rats received PBS only and served as controls for the experiment. Two days after the last instillation the animals were sacrificed and the orbital contents prepared for immunohistological staining. A panel of monoclonal antibodies was used: CD5, CD4, CD8, CD25, and CD45RA. The number of positive cells were counted in sections of epibulbar, forniceal, and tarsal conjunctiva. Results: There was a significant increase in the number of CD8 T lymphocytes in the conjunctiva of animals receiving retinal S-antigen when compared to control animals. Conclusion: Conjunctival instillation of retinal S-antigen causes an immune response in the C-MALT with a significant increase in the CD8 T lymphocyte subset in this tissue. This response may be involved in the induction of tolerance to the encountered antigen.

Chronic IL9 and IL-13 Exposure Leads to an Altered Differentiation of Ciliated Cells in a Well-Differentiated Paediatric Bronchial Epithelial Cell Model

Asthma is a chronic inflammatory disease characterised by airways remodelling. In mouse models IL-9 and IL-13 have been implicated in airways remodelling including mucus hypersecretion and goblet cell hyperplasia. Their role, especially that of IL-9, has been much less studied in authentic human ex vivo models of the bronchial epithelium from normal and asthmatic children. We assessed the effects of IL-9, IL-13 and an IL-9/IL-13 combination, during differentiation of bronchial epithelial cells from normal (n?=?6) and asthmatic (n?=?8) children. Cultures were analysed for morphological markers and factors associated with altered differentiation (MUC5AC, SPDEF and MMP-7). IL-9, IL-9/IL-13 combination and IL-13 stimulated bronchial epithelial cells from normal children had fewer ciliated cells [14.8% (SD 8.9), p?=?0.048, 12.4 (SD 6.1), p?=?0.016 and 7.3% (SD 6.6), p?=?0.031] respectively compared with unstimulated [(21.4% (SD 9.6)]. IL-9 stimulation had no effect on goblet cell number in either group whereas IL-9/IL-13 combination and IL-13 significantly increased goblet cell number [24.8% (SD 8.8), p?=?0.02), 32.9% (SD 8.6), p?=?0.007] compared with unstimulated normal bronchial cells [(18.6% (SD 6.2)]. All stimulations increased MUC5AC mRNA in bronchial epithelial cells from normal children and increased MUC5AC mucin secretion. MMP-7 localisation was dysregulated in normal bronchial epithelium stimulated with Th2 cytokines which resembled the unstimulated bronchial epithelium of asthmatic children. All stimulations resulted in a significant reduction in transepithelial electrical resistance values over time suggesting a role in altered tight junction formation. We conclude that IL-9 does not increase goblet cell numbers in bronchial epithelial cell cultures from normal or asthmatic children. IL-9 and IL-13 alone and in combination, reduce ciliated cell numbers and transepithelial electrical resistance during differentiation of normal epithelium, which clinically could inhibit mucociliary clearance and drive an altered repair mechanism. This suggests an alternative role for IL-9 in airways remodelling and reaffirms IL-9 as a potential therapeutic target.© 2013 Parker et al.

Metabolomic Profiling of In Vivo Plasma Responses to DioxinAssociated Dietary Contaminant Exposure in Rats: Implications for Identification of Sources of Animal and Human Exposure

Dioxin contamination of the food chain typically occurs when cocktails of combustion residues or polychlorinated biphenyl (PCB) containing oils become incorporated into animal feed. These highly toxic compounds are bioaccumulative with small amounts posing a major health risk. The ability to identify animal exposure to these compounds prior to their entry into the food chain may be an invaluable tool to safeguard public health. Dioxin-like compounds act by a common mode of action and this suggests that markers or patterns of response may facilitate identification of exposed animals. However, secondary co-contaminating compounds present in typical dioxin sources may affect responses to compounds. This study has investigated for the first time the potential of a metabolomics platform to distinguish between animals exposed to different sources of dioxin contamination through their diet. Sprague-Dawley rats were given feed containing dioxin-like toxins from hospital incinerator soot, a common PCB oil standard and pure 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (normalized at 0.1 µg/kg TEQ) and acquired plasma was subsequently biochemically profiled using ultra high performance liquid chromatography (UPLC) quadropole time-of-flight-mass spectrometry (QTof-MS). An OPLS-DA model was generated from acquired metabolite fingerprints and validated which allowed classification of plasma from individual animals into the four dietary exposure study groups with a level of accuracy of 97-100%. A set of 24 ions of importance to the prediction model, and which had levels significantly altered between feeding groups, were positively identified as deriving from eight identifiable metabolites including lysophosphatidylcholine (16:0) and tyrosine. This study demonstrates the enormous potential of metabolomic-based profiling to provide a powerful and reliable tool for the detection of dioxin exposure in food-producing animals.

Variation in Rice Cadmium Related to Human Exposure.

Cereal grains are the dominant source of cadmium in the human diet, with rice being to the fore. Here we explore the effect of geographic, genetic, and processing (milling) factors on rice grain cadmium and rice consumption rates that lead to dietary variance in cadmium intake. From a survey of 12 countries on four continents, cadmium levels in rice grain were the highest in Bangladesh and Sri Lanka, with both these countries also having high per capita rice intakes. For Bangladesh and Sri Lanka, there was high weekly intake of cadmium from rice, leading to intakes deemed unsafe by international and national regulators. While genetic variance, and to a lesser extent milling, provide strategies for reducing cadmium in rice, caution has to be used, as there is environmental regulation as well as genetic regulation of cadmium accumulation within rice grains. For countries that import rice, grain cadmium can be controlled by where that rice is sourced, but for countries with subsistence rice economies that have high levels of cadmium in rice grain, agronomic and breeding strategies are required to lower grain cadmium.

Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/µm on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately following irradiation in a dose-dependent manner. The analysis of repair capability showed that the cells irradiated with 1 and 2 Gy almost completely recovered from the damage, but not, however, 3 Gy treated cells in which DNA damage was not recovered. In addition, the results indicate the importance of the use of an appropriate control in radiobiological in vitro analysis.