Pheomelanin is widely thought to be causally related to susceptibility to the harmful effects of ultraviolet radiation: epidemiological studies show that those with a higher ratio of pheomelanin to eumelanin in hair have higher rates of melanoma, and work in mouse and cell culture shows that pheomelanin generates excess free radicals after UVR exposure. By contrast, based on measurements of eumelanin and pheomelanin in human skin, before and following irradiation, we now report that both pheomelanin and eumelanin are positively related to skin colour, and by inference, inversely with cancer susceptibility. The ratio of melanin classes is similar in people with widely different cancer rates and UVR sensitivity. Although our numbers are small, our results extend previous work in man, and lead us to speculate that factors other than the amount of pheomelanin may be important in determining UVR susceptibility in persons with red hair.
In the framework of the 2015 D3R inaugural grand challenge, blind binding pose and affinity predictions were performed for a set of 180 ligands of the Heat Shock Protein HSP90-α protein, a relevant cancer target. Spectral clustering was used to rapidly identify alternative binding site conformations in publicly available crystallographic HSP90-α structures. Subsequently, multiple docking and scoring protocols employing the software Autodock Vina and rDock were applied to predict binding modes and rank order ligands. Alchemical free energy calculations were performed with the software FESetup and Sire/OpenMM to predict binding affinities for three congeneric series subsets. Some of the protocols used here were ranked among the top submissions according to most of the evaluation metrics. Docking performance was excellent, but the scoring results were disappointing. A critical assessment of the results is reported, as well as suggestions for future similar competitions.
The dynamics of human pigmentation in response to ultraviolet radiation (UVR) remain poorly characterized. In part, this is attributable to methodological issues relating to the overlap in spectra of hemoglobin and melanin. We describe a new method, based on the recording of reflectance properties following iontophoresis of a potent vasoconstrictor, noradrenaline. This removes the influence of blood, allowing measurement of pigmentation, represented as L* on the L*a*b* scale. Blood flow was separately assessed using laser Doppler flowmetry. We show that there is a clear dose response with the dose of UVR administered, that pigmentation peaks at 1 wk and declines over the following 10 wk, but does not return to baseline within this period. We show clear differences in the degree, but not the temporal pattern of pigmentation between different pigmentary groups. We also report that the relation between facultative pigment and constitutive pigment is incomplete, with a wide scatter of responses for the development of pigmentation irrespective of constitutive levels. For comparison we also document overall photoadaptation and relate changes in pigmentation to the overall changes in photoadaptation.
This study has enabled us to study independently the pigmentary and non-pigmentary pathways and has shown that in those people with a lower degree of constitutive pigment, the primary mechanism of photoadaptation is via the non-pigmentary route.
Acidified nitrite cream results in the formation of S-nitrosocysteine throughout the treated nail. Acidified nitrite treatment makes a nail antifungal. S-nitrosothiols, formed by nitrosation of nail sulphur residues, are the active component. Acidified nitrite exploits the nature of the nail barrier and utilizes it as a means of delivery of NO/nitrosothiol-mediated antifungal activity. Thus the principal obstacle to therapy in the nail becomes an effective delivery mechanism.
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