996 resultados para toxicity screening


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It has been consistently reported that vegetable oils including canola oil have a life shortening effect in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) and this toxic effect is not due to the fatty acid composition of the oil. Although it is possible that the phytosterol content or type of phytosterol present in vegetable oils may play some role in the life shortening effect observed in SHRSP rats this is still not completely resolved. Furthermore supercritical CO2 fractionation of canola oil with subsequent testing in SHRSP rats identified safe and toxic fractions however, the compounds responsible for life shortening effect were not characterised. The conventional approach to screen toxic substances in oils using rats takes more than six months and involves large number of animals. In this article we describe how rapid bioassay-guided screening could be used to identify toxic substances derived from vegetable oils and/or processed foods fortified with vegetable oils. The technique incorporates sequential fractionation of oils/processed foods and subsequent treatment of human cell lines that can be used in place of animal studies to determine cytotoxicity of the fractions with structural elucidation of compounds of interest determined via HPLC-MS and GC-MS. The rapid bioassay-guided screening proposed would require two weeks to test multiple fractions from oils, compared with six months if animal experiments were used to screen toxic effects. Fractionation of oil before bio-assay enhances the effectiveness of the detection of active compounds as fractionation increases the relative concentration of minor components.

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The effects of increased trophic complexity, through the addition of predatory notonectids (Anisops deanei), on temporary pond microcosms used for aquatic toxicity testing were studied. Replicate microcosms were established using sediment from a dried temporary pond, and treated with one of four concentrations of the organochlorine pesticide endosulfan (0, 1, 10 or 50 μg/L), in the presence or absence of six A. deanei. The tanks were sampled regularly for nine weeks following the addition of the predators and the entire contents of each tank counted after 12 weeks. Analysis using non-metric multidimensional scaling (MDS) and non-parametric MANOVA showed that both Anisops and endosulfan at concentrations >10 μg/L significantly altered community structure. However, an interaction between the effects of Anisops and the effects of endosulfan was not detected. The addition of Anisops did not increase the variability of response and thus did not reduce the sensitivity of the test method.

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Introduction:
Cervical cancer screening has been implemented for over a decade in Australia and has significantly reduced the mortality and morbidity of the disease. The emergence of new technologies for cervical cancer, such as the Human Papillomavirus (HPV) vaccine and DNA testing has encouraged debate regarding the effective use of resources in cervical cancer prevention. The present study evaluates the cost-effectiveness, from a health sector perspective, of various screening strategies in the era of these new technologies.

Methods:
A stochastic epidemiological model using a discrete event and continuous algorithm was developed to describe the natural history of cervical cancer. By allowing one member of the cohort into the model at a time, this micro-simulation model encompasses the characteristics of heterogeneity and can track individual life histories. To evaluate the cost-effectiveness of the HPV vaccine a Markov model was built to simulate the effect on the incidence of HPV and subsequent cervical cancer. A number of proposed screening strategies were evaluated with the stochastic model for the application of HPV DNA testing, with changes in the screening interval and target population. Health outcomes were measured by Disability-Adjusted Life-Years (DALYs), adjusted for application within an evaluation setting (i.e. the mortality component of the DALY was adjusted by a disability weight when early mortality due to cervical cancer is avoided). Costs in complying with the Australian updated guidelines were assessed by pathway analysis to estimate the resources associated with cervical cancer and its pre-cancerous lesion treatment. Sensitivity analyses were performed to investigate the key parameters that influenced the cost-effectiveness results.

Results:
Current practice has already brought huge health gain by preventing more than 4,000 deaths and saving more than 86,000 life-years in a cohort of a million women. Any of the alternative screening strategies alter the total amount of health gain by a small margin compared to current practice. The results of incremental analyses of the alternative screening strategies compared to current practice suggest the adoption of the HPV DNA test as a primary screening tool every 3 years commencing at age 18, or the combined pap smear/HPV test every 3 years commencing at age 25, are more costly than current practice but with reasonable ICERs (AUD$1,810 per DALY and AUD$18,600 per DALY respectively). Delaying commencement of Pap test screening to age 25 is less costly than current practice, but involves considerable health loss. The sensitivity analysis shows, however, that the screening test accuracy has a significant impact on these conclusions. Threshold analysis indicates that a sensitivity ranging from 0.80 to 0.86 for the combined test in women younger than 30 is required to produce an acceptable incremental cost-effectiveness ratio.

Conclusions:
The adoption of HPV and combined test with an extended screening interval is more costly but affordable, resulting in reasonable ICERs. They appear good value for money for the Australian health care system, but need more information on test accuracy to make an informed decision. Potential screening policy change under current Australian HPV Vaccination Program is current work in progress. A Markov model is built to simulate the effect on the incidence of HPV and subsequent cervical cancer. Adoption of HPV DNA test as a primary screening tool in the context of HPV vaccination is under evaluation.

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Research on both sides of the Atlantic demonstrates that achieving high uptake of breast cancer screening remains an important area of public heath concern. UK government targets for breast screening uptake are 70%, however, much lower figures are found in many parts of the country, including South East London. This paper reports the findings of a study carried out to explore the views of women aged 50 to 64 (the age group covered by the free National Health Service screening programme) in order to: · establish in what way women who do not attend for screening are different from women who do attend · ascertain the views of the non-attenders with a view to making recommendations to the service which may help address the low uptake locally.

305 women were recruited through a variety of different community sources across the study area. Using a structured questionnaire/interview, women gave their views on their health concerns generally, as well as on breast screening in particular. The analysis (being undertaken now, to be completed by May 2005) will explore the influence of candidacy (women's assessment of the personal risk to them of their disease) on women's screening behaviour and the differences, if any, between the major ethnic groups in the area, indigenous white, black African and black Caribbean.

Learning Objectives:
# At the conclusion of the session, participants will be able to

* 1. Describe the factors associated with women’s screening behaviour
* 2. Evaluate the relevance of candidacy in understanding screening behaviour
* 3. Assess the relevance of UK findings for screening programmes elsewhere.