Apigenin prevents development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumors in Sprague-Dawley rats

The use of progestins as a component of hormone replacement therapy has been linked to an increase in breast cancer risk in postmenopausal women. We have previously shown that medroxyprogesterone acetate (MPA), a commonly administered synthetic progestin, increases production of the potent angiogenic factor vascular endothelial growth factor (VEGF) by tumor cells, leading to the development of new blood vessels and tumor growth. We sought to identify nontoxic chemicals that would inhibit progestin-induced tumorigenesis. We used a recently developed progestin-dependent mammary cancer model in which tumors are induced in Sprague-Dawley rats by 7,12-dimethylbenz(a)anthracene (DMBA) treatment. The flavonoid apigenin, which we previously found to inhibit progestin-dependent VEGF synthesis in human breast cancer cells in vitro, significantly delayed the development of, and decreased the incidence and multiplicity of, MPA-accelerated DMBA-induced mammary tumors in this animal model. Whereas apigenin decreased the occurrence of such tumors, it did not block MPA-induced intraductal and lobular epithelial cell hyperplasia in the mammary tissue. Apigenin blocked MPA-dependent increases in VEGF, and suppressed VEGF receptor-2 (VEGFR-2) but not VEGFR-1 in regions of hyperplasia. No differences were observed in estrogen or progesterone receptor (ER/PR) levels, or the number of estrogen receptor-positive cells, within the mammary gland of MPA-treated animals administered apigenin, MPA-treated animals, and placebo treated animals. However, the number of progesterone receptor-positive cells was reduced in animals treated with MPA or MPA and apigenin compared with those treated with placebo. These findings suggest that apigenin has important chemopreventive properties for those breast cancers that develop in response to progestins.     

Risk assessment of dietary exposure to methylmercury in fish in the UK

Risk assessment of chemicals in food is generally based upon the results of toxicological studies in laboratory animals, allowing for uncertainties relating to interspecies differences, human variability, and gaps in the database. Use of quantitative human data is preferable if available, as in the example of methylmercury. Methylmercury is a neurotoxic environmental contaminant, for which fish is the main source of dietary exposure. Human data from poisoning incidents and epidemiological studies have been used by expert committees to derive a guideline intake level for methylmercury, based on the susceptibility of the most sensitive lifestage, the developing fetus. In the UK, an expert group of nutritionists and toxicologists was formed to review the benefits and risks associated with fish consumption. A formal risk-benefit analysis was not possible because the nutritional data were not sufficiently quantitative. The Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT), therefore, modified the risk assessment approach to derive different guideline intake levels for different subgroups of the population. The COT opinion was used to provide targeted advice on how much fish can be consumed without undue risk from the contaminants. Consumption by adults of one weekly portion (140 g) of shark, swordfish or marlin, would lead to an exceedance of the guideline intake for methylmercury of 40-90%, set to protect the developing fetus, without considering intake from the rest of the diet. Pregnant women and women who may become pregnant within 1 year were, therefore, advised to avoid consumption of these species. Intakes in other adults would be within a higher guideline intake, set to protect groups of the population other than the developing fetus. However, consumption by children of one weekly portion of these species could lead to an exceedance of this guideline intake by up to 60%, without considering intake from the rest of the diet. It was, therefore, advised that consumption of these species by children should be avoided.     

Virtual neurosurgery, training for the future

Virtual reality (VR) simulators have been created for various surgical specialties. The common theme is extensive use of graphics, confined spaces, limited functionality and limited tactile feedback. A development team at the University of Nottingham, UK, consisting of computer scientists, mechanical engineers, graphic designers and a neurosurgeon, set out to develop a haptic, e.g. tactile simulator for neurosurgery making use of boundary elements (BE). The relative homogeneity of the brain, allows boundary elements, e.g. 'surface only' rendering, to simulate the brain structure. A boundary element simplifies the computing equations saves computing time, by assuming the properties of the surface equal the properties of the body. A limited audit was done by neurosurgical users confirming the potential of the simulator as a training tool. This paper focuses on the application of the computational method and refers to the underlying mathematical structure. Full references are included regarding the mathematical methodology.