Maternal miRNA-146a G/C rs2910164 variation, HIV/AIDS and nitrogen oxide pollution exposure collectively affects foetal growth.

OBJECTIVE:: Nitrogen oxide (NOx) pollution and human immunodeficiency virus (HIV)/AIDS intensify inflammation during pregnancy and linked with adverse birth outcomes (ABOs). MicroRNA (miRNA)-146a plays a crucial role in regulating inflammation in the NF-κB pathway. The G/C rs2910164 dampens miRNA-146a activity and linked with inflammatory diseases. The present study investigated whether HIV/AIDS and NOx exposure throughout pregnancy further intensifies ABO in Black South African women genotyped for the rs2910164. METHODS:: Pregnant women ( n = 300) were subdivided into low, medium and high NOx exposure groups, genotyped for the miRNA-146a G/C rs2910164 using polymerase chain reaction-restriction fragment length polymorphism, and further stratified based on HIV status. RESULTS:: Unstratified data (HIV+ and HIV- mothers combined): Mothers from the high NOx group with the variant C-allele had low blood iron levels ( p = 0.0238), and had babies with reduced birthweights ( p = 0.0283). As NOx increased, the prevalence of preterm birth and low birth weight also increased in mothers with the variant C-allele versus wildtype G-allele. HIV-infected mothers: In all NOx exposure groups, mothers with the variant C-allele had higher systolic blood pressure (low: p = 0.0386, medium: p = 0.0367 and high: p = 0.0109) and had babies with lower Appearance, Pulse, Grimace, Activity and Respiration scores at 1 min (low: p = 0.0190, medium: p = 0.0301 and high: p = 0.0361). CONCLUSION:: Maternal rs2910164 variant C-allele, NOx pollution and HIV/AIDS might collectively play a role in intensifying gestational hypertension and ABO.

IL-17A[G197G]-Association between NOx and gestational age in a South African birth cohort.

Interleukin (IL-)17A, plays a role in pathogenic defence, but is implicated in chronic inflammatory diseases, and has recently been associated with variable pregnancy outcomes. We investigated the role of maternal IL-17-[G197A]-specific effects of third-trimester IL-17 mRNA expression, NOx exposure levels and other variables on gestational age, in the Mother and Child in the Environment (MACE) birth cohort in South Africa. A total of 327 participants were genotyped for IL-17-[G197A] by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP). Quantitative real-time PCR was used to quantitate IL-17-mRNA expression in whole blood. Multivariate linear regression analysis, stratified by IL-17-[G197A] genotype, was used to test for effects of NOx , IL17A/GAPDH, haemoglobin, body mass index, HIV-1 positivity, maternal education and income level on gestational age. Lower expression was associated with the IL-17-GG versus GA in the cohort and HIV-1-negative group (p = .0007, p = .0058), while no difference was observed in the HIV-1 positives. Elevated IL-17A expression was observed in the high NOx exposure groups, within IL-17[G197G] (p = .0004). IL-17[G197G] was associated with PTB (p < .0001), and the PTB group had lower IL-17A expression compared to the full-term group (p = .0002). IL-17 expression was associated with an increase in gestational age (p = .038), and NOx was associated with a decrease in gestational age in the IL-17[G197G] model (p = .046).

IL-1ß haplotype influences the effect of NOx exposure on gestational age in the South African MACE birth cohort.

OBJECTIVE: Cytokines, molecules within the immune system that affect either a pro- or anti-inflammatory response, have previously been shown to influence birth outcomes. The maternal cytokine gene-environment interactions are thought to alter their expression, potentially influencing susceptibility to adverse birth outcomes. The aim of this study was to determine the association between the maternal interleukin-1ß (IL-1ß) haplotype and expression variation with oxides of nitrogen (NOx) levels, and thereafter investigate the IL-1ß haplotype-specific effects of NOx exposure levels, IL-1ß mRNA expression and other variables on gestational age. MATERIAL AND METHODS: Using the prospective Mother and Child in the Environment (MACE) birth cohort in Durban, South Africa, 335 participants were genotyped for the IL-1ß haplotype. Previous studies showed that three single nucleotide polymorphisms (SNPs), IL-1ß-1464G/C, -511C/T and -31C/T, constitute the IL-1ß functional haplotype. These SNPs were genotyped using a restriction fragment length polymorphism assay, while IL-1ß mRNA expression was measured using a quantitative real-time polymerase chain reaction assay. Individual estimates of NOx exposure were obtained by land use regression modelling. A multivariate linear regression analysis was employed to test for significant effects on gestational age. RESULTS: IL-1ß mRNA expression was found to possess a haplotype-dependent effect ( p = 0.0001) and its expression levels positively correlated with NOx levels ( r = 0.34; p = 0.006). In the high haplotype model, a unit increase in NOx exposure level was associated with a decrease in gestational age by 1 week ( p = 0.02). Furthermore, gestational age decreased by 0.9 weeks for every unit increase of IL-1ß mRNA expression level ( p = 0.025). HIV-1 positivity was associated with a 0.2-week decrease in gestational age ( p = 0.035) in the intermediate haplotype model and a 0.4-week decrease in the high haplotype model ( p = 0.044). CONCLUSION: These data have implications for better understanding the effect of prenatal NOx exposure on gestational age and demonstrate the role of the IL-1ß haplotype in modulating the effects of NOx exposure.

Naringenin attenuates highly active antiretroviral therapy-induced sperm DNA fragmentations and testicular toxicity in Sprague-Dawley rats.

Highly active antiretroviral therapy has evolved over the years, leading to a boost in the quality of life in people living with HIV and AIDS. However, growing evidence has shown that highly active antiretroviral therapy has deleterious effects on the testes and the overall reproductive capacity. Therefore, this study is to determine the adjuvant potential of Naringenin on highly active antiretroviral therapy-induced perturbations in fertility of male Sprague-Dawley rats. Thirty adult male Sprague-Dawley rats were divided into six groups viz - Control; H: 30 mg/kg of highly active antiretroviral therapy (EFV, 600 mg + FTC, 200 mg + TDF, 300 mg); N40: Naringenin, 40 mg/kg; N80: Naringenin, 80 mg/kg; HN40: highly active antiretroviral therapy + Naringenin, 40 mg/kg; HN80: highly active antiretroviral therapy + Naringenin, 80 mg/kg. The rats were euthanized after 4 weeks. Results showed that there was a significant decrease in sperm count (p < 0.001), spermatozoa with normal morphology (p < 0.001) and progressive sperm motility (p < 0.05) of H compared to the control and the HN groups. Likewise, fragmentations increased (p < 0.05) in tail lengths of sperm DNA in H compared to control. HN40 and HN80 decreased tail lengths compared to H (p < 0.001). There was also a decrease in %tail DNA and tail moment in HN40 (p < 0.001) compared to H. Luteinizing hormone significantly increased (p < 0.05) in HN40, HN80, and N40 (p < 0.001) but decreased in H (p < 0.05) compared to control. The diameter of the seminiferous tubules also decreased (p < 0.05) in H compared to control, N80, and HN40. Likewise, the area of the seminiferous tubules in group H decreased (p < 0.05) compared to N80 and HN80. The seminiferous tubules epithelium increased (p < 0.05) in N40 and HN40 compared to H. This study establishes that highly active antiretroviral therapy has deleterious effects on the testicular microanatomy, sperm parameters, and sperm DNA of Sprague-Dawley rats, which may impair fertility but Naringenin is a potential complimentary adjuvant.

Concentration-dependent effect of fumonisin B1 on apoptosis in oesophageal cancer cells.

The geographical distribution of oesophageal cancer is linked to the exposure of fumonisin B1 (FB1), a mycotoxin produced by fungi that contaminates staple food worldwide. Non-genotoxic carcinogens like FB1 disturb homeostasis through increased cell proliferation or suppression of apoptosis. This study investigated the involvement of FB1 (0-20 µM) in spindle-shaped N-cadherin (+) CD45 (-) osteoblastic (SNO) cell death. Cell viability and death were assessed using the MTS and Annexin V-Fluos assays, respectively. Caspase activities were determined luminometrically and the comet assay assessed DNA damage. Induction of oxoguanine glycosylase 1 (OGG1) was measured using quantitative Polymerase Chain Reaction (qPCR), while cleaved poly (ADP-ribose) polymerase 1 (PARP-1) and Bax were determined by western blotting. Cell viability and PARP-1 cleavage were not affected by 1.25 µM FB1, but phosphatidylserine externalization, Bax protein expression, caspase activity, comet tail length and OGG1 transcripts were increased. The reduced cell viability in 10 µM FB1-treated cells was accompanied by corresponding increases in externalized phosphatidylserine, Bax, caspase-3/7 activity and cleaved PARP-1. The OGG1 transcripts were not significantly increased, but comet tails were increased. Bax, caspase-3/7 activities and cleaved PARP-1 were inhibited at 20 µM FB1. In addition, the OGG1 transcript levels were decreased ( p < 0.0001) along with comet lengths ( p < 0.0001). This study showed that FB1-induced apoptosis in SNO cells may be caspase-dependent or caspase-independent; the pathway used depends on the exposure concentration.

Phytonanotherapy for management of diabetes using green synthesis nanoparticles.

The world has a rich diversity of indigenous medicinal plants. The World Health Organization (WHO) gives high priority to eco-friendly, non-hazardous and cost effective healthcare such as the use of medicinal plants to treat various illnesses, including Human immunodeficiency virus (HIV) infection and Acquired immune deficiency syndrome (AIDS), tuberculosis (TB), diabetes mellitus (DM), malaria, and cancer. In developing countries, a high proportion of the population tends to use complementary and alternative medicines (CAM) together with conventional prescription drugs. Globally, CAM has been used in both developed and developing countries. In China, 30-50% of medicinal use is based on traditional alternative medicine. In Africa, it is estimated that 80% of primary health care is CAM, whilst in the USA, about 158 million people us CAM. This increase is due to three main influences: improve their eminence of life, relieve symptoms and preclude long-term complications. Despite the advances and advantages of conventional pharmaceutical medication, these are associated with long-term side effects and pose risks of inefficacy for treatment of chronic diseases such as cancer and DM. The biosynthesis of metal nanoparticles (NPs) using medicinal plants has received considerable attention as a proper alternative to using hazardous chemical and physical synthetic techniques. Plants are being exploited for their unique metal tolerance and effective production of gold metal NPs. A single medicinal plant contains an orchestra of chemical elements (e.g. proteins, vitamins, enzymes, amino acids, polysaccharides and organic compounds) that are "environmentally benign, yet chemically complex" and therefore serve as ideal tools for enhanced medicinal applications. It is reported that phytocompounds such as terpenoids, polysaccharides, polyols and flavones take part in the bio-reduction, stabilization and bio-capping mechanisms to form stable gold and silver NPs. Also the inhibitory potential of plant compounds against diabetic targets followed by a study of enzyme inhibitor kinetics, ligand binding dynamics supported by in silico docking studies that reveal the mode of bioactive compounds and their inhibitory activities. The present review focuses on the potential anticancer, antidiabetic and antimicrobial activity of phyto-synthesized gold and silver NPs. In phytonanotherapy, synergistic features of plant and metal NPs are unique as they offer healing properties that may be the clinical bioequivalent to many synthetic drugs, with minimal side effects. This could provide alternative treatment for chronic diseases that is efficient to overcome the disadvantages of synthetic monotherapy and allows medicinal plant therapy to co-exist with current synthetic treatments. This creates a much needed paradigm shift for further clinical studies in non-communicable and communicable diseases.

Biosynthesis and computational analysis of amine-ended dual thiol ligand functionalized gold nanoparticles for conventional spectroscopy detection of melamine.

The bio-synthesized DTAuNPs have an average size of 21nm. The aggregation extent depends on the concentration of melamine, which was validated by UV-vis spectra and visual method of melamine detection was developed. The major observation in this method was the color change of DTAuNPs from red to purple due to the aggregation of ligand capped gold nanoparticles instigated by melamine. The reaction of color changes were processed due to the shifting of bonding in hydrogen in between nanoparticles and melamine. The aggregation extent depends on the concentration of melamine, which can be validated UV-vis spectra and visual method of detecting melamine is developed. The electron density and conventional UV-vis, FTIR spectroscopy and DFT studies on the ligand was performed using computational methods. The theoretical and experimental data for the energy transitions and the molar extinction coefficients of the ligands studied has been obtained. Further, the ligand capped gold nanoparticles was assessed for cytotoxicity against A549 cells which resulted in significant decrease in cell viability was noted in 50µg/mL DTAu, 4-ATP and AXT treated cells at 2h (85% and 66%) and 6h (83% and 36%) respectively, (p<0.01) were studied and reported in this manuscript.

Patulin triggers NRF2-mediated survival mechanisms in kidney cells.

Patulin (PAT), a mycotoxin contaminant of apples and apple products, has been implicated in nephrotoxicity. PAT depletes glutathione (GSH) and elevates reactive oxygen species (ROS). The antioxidant (AO) response is activated by Nuclear erythroid 2-related factor (NRF2) and enhanced by Silent information regulator 3 (SIRT3). The effects of PAT on these molecules have yet to be examined. We investigated the effects of PAT on AO response survival pathways in human embryonic kidney cells (HEK293). PAT cytotoxicity on HEK293 cells was evaluated (MTT assay; 24 h; [0-100 µM]) to determine an IC50. GSH levels were measured using luminometry. Intracellular ROS was evaluated by flow cytometry. Protein expression of Keap1, NRF2, SIRT3 and PGC-1α was quantified by western blotting and gene expression of SOD2, CAT and GPx was evaluated by qPCR. PAT caused a dose dependent decrease in HEK293 cell viability and a significant increase in levels of intracellular ROS (p = 0.0006). A significant increase in protein expression (p = 0.029) was observed. PAT increased gene expression of SOD2 and CAT (p = 0.0043), however, gene expression of GPx was significantly reduced (p = 0.0043). These results show the up-regulation of NRF2 mediated AO mechanisms in response to PAT toxicity.

Telomeres and atherosclerosis.

In humans and other multicellular organisms that have an extended lifespan, the leading causes of death are atherosclerotic cardiovascular disease and cancer. Experimental and clinical evidence indicates that these age-related disorders are linked through dysregulation of telomere homeostasis. Telomeres are DNA protein structures located at the terminal end of chromosomes and shorten with each cycle of cell replication, thereby reflecting the biological age of an organism. Critically shortened telomeres provoke cellular senescence and apoptosis, impairing the function and viability of a cell. The endothelial cells within atherosclerotic plaques have been shown to display features of cellular senescence. Studies have consistently demonstrated an association between shortened telomere length and coronary artery disease (CAD). Several of the CAD risk factors and particularly type 2 diabetes are linked to telomere shortening and cellular senescence. Our interest in telomere biology was prompted by the high incidence of premature CAD and diabetes in a subset of our population, and the hypothesis that these conditions are premature-ageing syndromes. The assessment of telomere length may serve as a better predictor of cardiovascular risk and mortality than currently available risk markers, and anti-senescence therapy targeting the telomere complex is emerging as a new strategy in the treatment of atherosclerosis. We review the evidence linking telomere biology to atherosclerosis and discuss methods to preserve telomere length.

Effects of Persea americana Mill (Lauraceae) ["Avocado"] ethanolic leaf extract on blood glucose and kidney function in streptozotocin-induced diabetic rats and on kidney cell lines of the proximal (LLCPK1) and distal tubules (MDBK).

Extracts of Persea americana Mill (Lauraceae) ("Avocado") have been traditionally used to treat hypertension and diabetes mellitus. Accordingly, we studied the hypoglycaemic and renal function effects of P. americana leaf ethanolic extracts (PAE) in STZ-induced diabetic rats. Oral glucose tolerance responses to various doses of PAE were monitored in fasted rats following a glucose load. Rats treated with deionized water or standard hypoglycaemic drugs acted as untreated and treated positive controls, respectively. Acute renal effects of PAE were investigated in anesthetized rats challenged with 0.077 M NaCl after a 3.5-h equilibration for 4 h comprising 1 h control, 1.5 h treatment and 1.5 h recovery periods. PAE was added to the infusate during the treatment period. Hepatic glycogen concentration was measured after 6 weeks of daily treatment with PAE. PAE induced dose-dependent hypoglycaemic responses in STZ-induced diabetic rats while subchronic PAE treatment additionally increased hepatic glycogen concentrations. Acute PAE infusion decreased urine flow and electrolyte excretion rates, whilst subchronic treatment reduced plasma creatinine and urea concentrations. These results indicate not only the basis of the ethnomedicinal use of P. americana leaf extract in diabetes management, but also of need for further studies to identify and evaluate the safety of PAE's bioactive compounds.

Sclerocarya birrea [(A. Rich.) Hochst.] [Anacardiaceae] stem-bark ethanolic extract (SBE) modulates blood glucose, glomerular filtration rate (GFR) and mean arterial blood pressure (MAP) of STZ-induced diabetic rats.

Studies in our laboratories suggest that Sclerocarya birrea stem-bark ethanolic extract (SBE) has hypoglycemic properties. Accordingly, we investigated the effects of SBE on major complications of diabetes mellitus; blood glucose, renal function and mean arterial blood pressure (MAP) in non-diabetic and STZ-induced diabetic rats. Oral glucose tolerance test responses to various SBE doses (60, 120 and 240 mg kg(-1)) were studied in fasted rats following glucose load (0.86 g kg(-1), p.o.). Rats treated with deionized water (3 ml kg(-1) p.o.), or standard hypoglycemic drugs (insulin, 100 microg kg(-1), s.c.; metformin, 500 mg kg(-1), p.o. or glibenclamide, 500 microg kg(-1), p.o) acted as untreated and treated positive controls, respectively. Blood was collected in non-diabetic rats after 45 min of SBE, metformin or glibenclamide for plasma insulin determination. Acute SBE effects on renal function and MAP were studied in anesthetized rats challenged with hypotonic saline after 3.5h equilibration for 4h of 1h control, 1.5h treatment and 1.5h recovery periods. SBE was added to the infusate during the treatment period. Chronic effects were monitored for 5 weeks in animals daily treated with SBE (120 mg kg(-1) p.o.) while hepatic glycogen concentration was measured at the end of the experimental period. SBE exhibited dose-dependent reduction in blood glucose concentration. SBE and metformin did not affect plasma insulin secretion in non-diabetic rats, while glibenclamide increased plasma insulin concentration. The hypoglycemic effect of SBE treatment was associated with increased hepatic glycogen synthesis. Acute SBE administration did not significantly alter kidney function, but chronic SBE treatment for decreased plasma urea and creatinine concentrations of STZ-diabetic rats with concomitant increase in GFR by comparison with control rats at the corresponding period (0.7+/-0.2 vs. 1.4+/-0.3 ml min(-1)). SBE treatment reduced blood pressure in all groups of animals. The observations suggest that SBE has reno- and cardio-protective effects in diabetes mellitus. The current results indicate the basis for SBE use as complementary remedy in diabetes.

Effects of Ficus thonningii (Blume) [Morarceae] stem-bark ethanolic extract on blood glucose, cardiovascular and kidney functions of rats, and on kidney cell lines of the proximal (LLC-PK1) and distal tubules (MDBK).

Previous observations indicate that Ficus thonningii (Blume) [Moraceae] stem-bark extracts may be useful in the control of diabetes mellitus. Accordingly, we investigated in some experimental animal paradigms the effects of F. thonningii stem-bark ethanolic extract (FTE) on renal and cardiovascular functions as complications of diabetes. Oral glucose tolerance tests were conducted in separate groups of non-diabetic and STZ-treated diabetic rats given glucose load (0.86 g x kg(-1), p.o.) after 18-h fast, followed by various FTE doses (60, 120, and 240 mg x kg(-1)). Rats treated with deionized water (3 mL x kg(-1) p.o.), or metformin (500 mg x kg(-1) p.o.) acted as untreated and treated positive controls, respectively. Blood glucose was monitored at 15-min intervals for the first hour, and hourly thereafter for 3 h. Acute effects of FTE on kidney function and mean arterial blood pressure (MAP) were investigated in anaesthetized rats challenged with hypotonic saline after a 3.5-h equilibration for 4 h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. FTE was added to the infusate during the treatment period. Chronic effects of FTE were studied in individually caged rats treated daily with FTE (120 mg x kg(-1), p.o.) for five weeks. Cytotoxicity of FTE was assessed by dye-reduction colorimetric (MTT) assay on MDBK and LLCPK1 kidney cell lines exposed for 24 h, 48 h, and 72 h to graded concentrations of the extract. Myocardial contractile performance was evaluated on rat isolated atrial muscle strips. FTE, like metformin, decreased blood glucose levels in non-diabetic and STZ-diabetic rats. Both acute and chronic FTE treatments did not affect renal function. In vitro studies demonstrated that FTE increased MDBK cell metabolic activity by an average of 15% (72 h), and LLCPK1 mirrored the controls. Acute intravenous infusion of FTE reduced the MAP from 119 +/- 1 mmHg to 98 +/- 4 mmHg. The MAP also was reduced throughout the five-week experimental study period. FTE also produced concentration-dependent, negative inotropic and chronotropic effects on rat isolated, electrically driven left-, and spontaneously beating right-, atrial muscle preparations. Our experimental findings suggest that FTE possesses reno- and cardio-protective effects in diabetes mellitus.

Prolonged exercise does not cause lymphocyte DNA damage or increased apoptosis in well-trained endurance athletes.

Recent research has demonstrated that lymphocyte apoptosis sensitivity appears to be related to training status and exercise intensity. This work investigated the effect of prolonged, submaximal treadmill running on percentage (%) apoptosis, % necrosis and DNA strand breaks in lymphocytes and related these to changes in total lymphocyte and blood cortisol concentrations in well-trained runners. Venous blood samples (n = 14) were taken immediately before (PRE), immediately after (IPE) and 3 h after (3PE) 2.5 h of treadmill running at 75% of VO2 max from eight well-trained male endurance athletes (age 34.2 +/- 2.44 years) and analysed for cellular content and serum cortisol concentrations. Lymphocytes were isolated from whole blood and % apoptotic and necrotic cell were detected by flow cytometry using Annexin V-FITC and propidium iodide uptake. DNA strand breaks were measured by single-cell gel electrophoresis. Despite a significant (P < 0.001) exercise-induced increase in mean serum cortisol concentrations and reduction in lymphocyte counts, the mean % Annexin-V positive cells (13.3 +/- 6.78 in PRE, 11.3 +/- 5.51 in IPE and 12.8 +/- 6.75 in 3PE samples) were not significantly different at the three time-points (P > 0.05). Mean DNA strand breaks in the lymphocytes also did not change significantly (P > 0.05) rising from 25.7 +/- 2.16 to 26.9 +/- 1.89 and 27.1 +/- 1.38 microm in IPE and 3PE samples, respectively. The exercise-induced changes in total blood lymphocyte counts and cortisol concentrations did not result in a significant change in % apoptotic lymphocytes or DNA strand breaks in the endurance-trained athletes during this prolonged, submaximal exercise.

Cytotoxicity of aflatoxin B1 and its chemically synthesised epoxide derivative on the A549 human epithelioid lung cell line.

Aflatoxin B1 (AFB1 ) is a carcinogenic mycotoxin found in feeds and in airborne grain dusts. Aflatoxin B1 requires biotransformation to the AFB1-8,9 epoxide (AFBO) by a bioactivation system and subsequent covalent binding to DNA or proteins, to exert its carcinogenic potential. The lung contains cytochrome P450, prostaglandin-H-synthase, lipoxygenase, epoxide hydrolase and other bioactivation enzymes, and is thus a potential target for the effects of AFB1 via the routes of inhalation and ingestion. The A549 human epithelioid lung cell line and the methylthiazol tetrazolium (MTT) bioassay were used to investigate the cytotoxicity of AFB1 and its chemically synthesised epoxide (AFBO) in vitro. Statistical analysis of the MTT results indicated that there were overall significant differences between the control and both the AFB1-treated (p < 0.0001) and AFBO-treated cells (p = 0.002). However, there was no significant difference between AFB1 and AFBO-treated cells, when the entire range of concentrations were assessed against each other (p = 0.2877). When analysed at each concentration, only at 0.01 mM was there a significant difference between the effects of AFB1 and AFBO (p = 0.0358). The results of this investigation show that AFB1 and AFBO are both cytotoxic in the A549 cell line.

Exposure of rural and urban populations in KwaZulu Natal, South Africa, to fumonisin B(1) in maize.

We surveyed households in rural and urban areas of KwaZulu Natal, South Africa, to assess the exposure of the inhabitants to fumonisin B(1) (FB(1)), a mycotoxin produced by Fusarium verticillioides. In southern African regions maize, used as a staple food by the population, is prone to F. verticillioides infection. Furthermore, high levels of FB(1) in maize have been associated with esophageal cancer in South Africa. We assessed exposure of the population to FB(1) at three levels, namely, by analyzing stored maize, plate-ready food, and feces. The positions of participating households in the rural area were recorded using geographic information systems (GIS) for ease and accuracy of follow-up. Of the 50 rural maize samples examined, 32% had levels of FB(1) ranging from 0.1-22.2 mg/kg, whereas 29% of the 28 cooked maize (phutu) samples contained FB(1) ranging from 0.1-0.4 mg/kg. The incidence and levels of FB(1) in feces were 33% and 0.5-39.0 mg/kg, respectively. Of the 49 urban maize samples analyzed 6.1% had a range of 0.2-0.5 mg/kg FB(1), whereas 3 of 44 fecal samples (6%) ranged between 0.6 and 16.2 mg/kg. No FB(1) was detected in urban phutu samples. Because these levels are lower than those published from regions in South Africa with high incidence of esophageal cancer, it may be concluded that the risk of esophageal cancer from FB(1) exposure is lower in the KwaZulu Natal region.

The determination of fumonisin B1 in human faeces: a short term marker for assessment of exposure.

Fumonisin B1 (FB1) is a compound that occurs frequently in rural foods and feeds, creating health hazards. When ingested, FB1 does not appear to change in structure and is mostly excreted unchanged in faeces within 24 h. Twenty human stool samples obtained from rural school children of Vulamehlo, south of Durban (South Africa), were analysed for FB1, as well as 23 urban control samples obtained from various households within the Durban metropolitan area. The samples were freeze-dried and ground to a fine powder. A fraction of each sample was extracted three times with aqueous ethylenediaminetetraacetic acid at pH 5.2. The pooled extracts were purified using reversed phase C18 solid phase extraction cartridges. Analytical high performance liquid chromatography was used to quantitate the amount of FB1 as an o-phthaldialdehyde (OPA) derivative in the extracts. The rural (35%) and the urban samples (9%) showed the presence of FB ranging from 790 to 19 560 ng g(-1) of freeze dried stool. It was concluded that this method could be used as a routine biomarker for short term human exposure to FB1 in contaminated food.

Synthesis of sterigmatocystin derivatives and their biotransformation to aflatoxins by a blocked mutant of Aspergillus parasiticus.

Seven alkyl and aryl homologues of O-methylsterigmatocystin (OMST) were synthesised and fed in separate experiments to a mutant of Aspergillus parasiticus capable of converting sterigmatocystin (ST) to aflatoxin B1 (AFB1). Their conversion to AFB1 was followed over a time period and it was found that O-propylsterigmatocystin (OPRST) was converted to AFB1 more rapidly than O-ethylsterigmatocystin (OEST) or OMST or ST itself. The aryl derivative O-benzoylsterigmatocystin (OBzST) was converted at the slowest rate. These results show that alkyl and aryl homologues of OMST may be converted to AFB1, suggesting that the methylation of ST is not an absolute requirement for its conversion to AFB1. It seems likely that whatever enzyme(s) are involved in this process exhibit relative specificity. As to whether alkylation of ST is an obligatory step in AFB1 biosynthesis is neither supported nor disproved as the fungal cells used are presumably capable of methylating ST. The fact that the propyl derivative showed fastest conversion is not necessarily significant as this may be due to faster diffusion of the least polar of the derivatives through the cell membrane.

The response of the dietary anti-oxidants vitamin E and vitamin C to oxidative stress in pre-eclampsia.

The relationship of oxidants and anti-oxidants in preeclampsia with reference to the dietary anti-oxidants vitamin C and vitamin E was investigated. Three groups of patients were studied in the third trimester of pregnancy: normotensives ( n = 32), mild pre-eclamptics ( n = 15) and severe pre-eclamptics ( n = 31) with a group of healthy non-pregnant women ( n = 18) serving as a control. Total anti-oxidant concentration, the concentrations of vitamin C, vitamin E, superoxide dismutase, uric acid and the concentration of total oxidant activity, as reflected by lipid peroxides, were measured in plasma or red blood cells. Total anti-oxidants and vitamin C concentrations were significantly lower in pre-eclamptic patients than in pregnant controls (P < 0.05), with the concentrations in the pregnant controls being significantly lower than in the non-pregnant controls (P < 0.05). There was no significant difference in vitamin E concentration for all four groups. Superoxide dismutase activity was significantly lower in the normal pregnancy group. Lipid peroxides were significantly increased in the three pregnant groups (P < 0.05) with no differences noted between these groups. The relationship of oxidants to anti-oxidants in pregnancy and pre-eclampsia is dependent on many factors but balance appears to be upset in pre-eclampsia. The reduction in anti-oxidant concentrations in pre-eclampsia suggests either a primary deficit or consumption of the anti-oxidants measured. Of the dietary anti-oxidants studied, vitamin C was most affected in pre-eclampsia.