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Neutrons help explain why antibiotics prescribed for chemotherapy cause kidney failure
Date:10/29/2012

und to penetrate more deeply into the fungal membranes than the human membranes at the same relatively low dose. The implication is that at such low doses during treatment, the AmB can open up holes in fungal cells but is unable to do so as readily in the human cells. Only when the dose is increased do you get holes passing right across both types of membranes and the resulting damage to healthy tissue.

The underlying cause of this difference in membrane insertion may be down to differences in the angle of insertion, identified for the first time in this paper. When the AmB inserts into the fungal (ergosterol-containing) membranes, it appears to be less tilted than when it inserts into the human (cholesterol-containing) membranes.

The next step for Dr Barlow is to improve the resolution of the analysis in order to identify the exact part of the drug which forms these barrel structures. It is this part that drug developers would need to play with to improve AmB's specificity to fungal cells, or use to develop a whole new drug with less harmful side effects.

Dr David Barlow from King's said: 'These are particularly harmful and potentially lethal side effects. The problem is, despite being developed in the 50's, no-one up until now has been able to experimentally determine how AmB works. This is vital if we are to reduce its complications or use its therapeutic properties in new less harmful, drugs.'

Dr Bruno Dem, a scientist at the ILL who worked with Dr Barlow on ILL's D16 neutron diffraction instrument said; 'Neutrons are an ideal tool for studying biological materials and their behaviour as proteins, viruses and cell membranes, all of the order of 1 to 10 nanometres, easily fall within the right size scale. Also neutrons are particularly sensitive to lighter atoms such as carbon, hydrogen and oxygen that make up these organic molecules and can distinguish between them very easily. With the world most powerful source of neutrons
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Contact: James Romero
james@proofcommunication.com
44-845-680-1866
King's College London
Source:Eurekalert  

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