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Tygerberg, South Africa

Khlangwiset P.,University of Pittsburgh | Shephard G.S.,PROMEC Unit | Wu F.,University of Pittsburgh
Critical Reviews in Toxicology | Year: 2011

Aflatoxins, fungal toxins produced by Aspergillus flavus and Aspergillus parasiticus in a variety of food crops, are well known as potent human hepatocarcinogens. Relatively less highlighted in the literature is the association between aflatoxin and growth impairment in children. Foodborne aflatoxin exposure, especially through maize and groundnuts, is common in much of Africa and Asiaareas where childhood stunting and underweight are also common, due to a variety of possibly interacting factors such as enteric diseases, socioeconomic status, and suboptimal nutrition. The effects of aflatoxin on growth impairment in animals and human children are reviewed, including studies that assess aflatoxin exposure in utero and through breastfeeding. Childhood weaning diets in various regions of the world are briefly discussed. This review suggests that aflatoxin exposure and its association with growth impairment in children could contribute a significant public health burden in less developed countries. © 2011 Informa Healthcare USA, Inc.

Somdyala N.I.,Burden of Disease Research Unit | Bradshaw D.,Burden of Disease Research Unit | Gelderblom W.C.,PROMEC Unit | Gelderblom W.C.,Stellenbosch University | Parkin D.M.,University of Oxford
International Journal of Cancer | Year: 2010

Cancer incidence rates and patterns are reported for a rural population, living in the Eastern Cape Province of South Africa for the period 1998-2002. The population-based cancer registry has operated for 20 years, using both active and passive methods for case finding, through collaborations with 19 health facilities: 11 district hospitals, 7 referral hospitals and 1 regional laboratory. The age standardized incidence rates for all cancers were 73.1 per 100,000 in males and 64.1 per 100,000 in females. The leading top 5 cancers for males were oesophagus (32.7 per 100,000), lung (5.8 per 100,000), prostate (4.4 per 100,000), liver (4.4 per 100,000) and larynx (2.5 per 100,000) whereas for females they were cervix (21.7 per 100,000), oesophagus (20.2 per 100,000), breast (7.5 per 100,000), ovary (0.9 per 100,000) and liver (0.9 per 100,000). The incidence of Kaposi sarcoma was low, and higher for males (1.6 per 100,000) than females (0.3 per 100,000). Lung cancer in both males and females was relatively low compared to the high incidence of oesophagus cancer. © 2010 UICC.

Ghiasian S.A.,Hamadan University of Medical Sciences | Ghiasian S.A.,Tehran University of Medical Sciences | Shephard G.S.,PROMEC Unit | Yazdanpanah H.,Tehran University of Medical Sciences
Mycopathologia | Year: 2011

Fifty-one maize samples, intended for animal feed and human consumption, were collected from the four main maize production provinces in Iran and analyzed by high-performance liquid chromatography (HPLC) for contamination by four naturally occurring aflatoxin analogues (AFB1, AFB2, AFG1, and AFG2). AFB1 was detected in 58.3, and 80% of the maize samples obtained from Kermanshah and Mazandaran provinces, respectively. The maximum AFB1 (276.3 μg/kg) and highest level of total aflatoxins (AFT) (316.9 μg/kg) were detected in a maize sample collected from Kermanshah province. The mean aflatoxin level from contaminated samples (52.60 μg/kg) from Kermanshah was significantly higher (P < 0.0001) than those in maize from the other three provinces and exceeded all the maximum tolerated levels (MTLs) set for AFT in maize. The level of AFB1 in 15.68% of the total samples was above the MTL (5 μg/kg) for AFB1 in maize in Iran. The mean contamination level of AFT (23.86 μg/kg) in the positive samples was higher than MTL for maize in Iran (20 μg/kg) intended for animal feed. The levels of AFB1, AFB2, AFG1, and AFG2 ranged between not detected (<0.1 μg/kg) and 276.3, 30.4, 9.1, and 1.1 μg/kg in maize grain, respectively. © 2011 Springer Science+Business Media B.V.

Schloms L.,Stellenbosch University | Storbeck K.-H.,Stellenbosch University | Swart P.,Stellenbosch University | Gelderblom W.C.A.,Stellenbosch University | And 2 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2012

The steroid hormone output of the adrenal gland is crucial in the maintenance of hormonal homeostasis, with hormonal imbalances being associated with numerous clinical conditions which include, amongst others, hypertension, metabolic syndrome, cardiovascular disease, insulin resistance and type 2 diabetes. Aspalathus linearis (Rooibos), which has been reported to aid stress-related symptoms linked to metabolic diseases, contains a wide spectrum of bioactive phenolic compounds of which aspalathin is unique. In this study the inhibitory effects of Rooibos and the dihydrochalcones, aspalathin and nothofagin, were investigated on adrenal steroidogenesis. The activities of both cytochrome P450 17α-hydroxylase/17,20 lyase and cytochrome P450 21-hydroxylase were significantly inhibited in COS-1 cells. In order to study the effect of these compounds in H295R cells, a human adrenal carcinoma cell line, a novel UPLC-MS/MS method was developed for the detection and quantification of twenty-one steroid metabolites using a single chromatographic separation. Under both basal and forskolin-stimulated conditions, the total amount of steroids produced in H295R cells significantly decreased in the presence of Rooibos, aspalathin and nothofagin. Under stimulated conditions, Rooibos decreased the total steroid output 4-fold and resulted in a significant reduction of aldosterone and cortisol precursors. Dehydroepiandrosterone-sulfate levels were unchanged, while the levels of androstenedione (A4) and 11β-hydroxyandrostenedione (11βOH-A4) were inhibited 5.5 and 2.3-fold, respectively. Quantification of 11βOH-A4 showed this metabolite to be a major product of steroidogenesis in H295R cells and we confirm, for the first time, that this steroid metabolite is the product of the hydroxylation of A4 by human cytochrome P450 11β-hydroxylase. Taken together our results demonstrate that Rooibos, aspalathin and nothofagin influence steroid hormone biosynthesis and the flux through the mineralocorticoid, glucocorticoid and androgen pathways, thus possibly contributing to the alleviation of negative effects arising from elevated glucocorticoid levels. © 2011 Elsevier Ltd. All rights reserved.

Van Der Westhuizen L.,PROMEC Unit | Shephard G.S.,PROMEC Unit | Gelderblom W.C.A.,PROMEC Unit | Gelderblom W.C.A.,Stellenbosch University | Riley R.T.,U.S. Department of Agriculture
World Mycotoxin Journal | Year: 2013

Maize is the predominant food source contaminated by fumonisins and this has particular health risks for communities consuming maize as a staple diet. The main biochemical effect of fumonisins is the inhibition of ceramide biosynthesis causing an increase in sphingoid bases and sphingoid base 1-phosphates and a depletion of the complex sphingolipids, thereby disrupting lipid metabolism and sphingolipid-mediated processes and signalling systems. Attempts to use the elevation of sphinganine as a human biomarker of fumonisin exposure have to date been unsuccessful. Consequently, recent research has focussed on developing a urinary exposure biomarker based on the measurement of the nonmetabolised toxin. In animals, fumonisins are poorly absorbed in the gut and are mostly excreted unmetabolised in faeces, with only a small percentage (0.25-2.0%) in urine. This appears to also be true in humans were fumonisin B1 (FB1) is detectable in urine soon after exposure, but in very small amounts relative to total intake. However, with modern sensitive and selective analytical methods such as liquid chromatography-tandem mass spectrometry, these low levels can be readily determined. The first study to show a positive correlation between consumption of maize and urinary FB 1 was conducted in a Mexican population consuming tortillas as a staple food. Further validation of this relationship was achieved in a South African subsistence farming community with a positive correlation between urinary FB1 and fumonisin exposure, as assessed by food analysis and food intake data. The most recent developments are aimed at measuring multiple mycotoxin biomarkers in urine, including FB1. Current exposure studies in Guatemala are combining the urinary biomarker with measurement of sphinganine-1-phosphate in blood spots as a measure of biochemical effect. Thus, the urinary FB1 biomarker could contribute considerably in assessing the adverse health impact of fumonisin exposure.

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