2 research outputs found
Release of Silver from Nanotechnology-Based Consumer Products for Children
We
assessed the potential for children’s exposure to bioavailable
silver during the realistic use of selected nanotechnology-based consumer
products (plush toy, fabric products, breast milk storage bags, sippy
cups, cleaning products, humidifiers, and humidifier accessory). We
measured the release of ionic and particulate silver from products
into water, orange juice, milk formula, synthetic saliva, sweat, and
urine (1:50 product to liquid mass ratio); into air; and onto dermal
wipes. Of the liquid media, sweat and urine yielded the highest amount
of silver release, up to 38% of the silver mass in products; tap water
yielded the lowest amount, ≤1.5%. Leaching from a blanket into
sweat plateaued within 5 min, with less silver released after washing.
Between 0.3 and 23 μg m<sup>–2</sup> of silver transferred
from products to wipes. Aerosol concentrations were not significantly
elevated during product use. Fabrics, a plush toy, and cleaning products
were most likely to release silver. Silver leached mainly via dissolution
and was facilitated in media with high salt concentrations. Levels
of silver to which children may potentially be exposed during the
normal use of these consumer products is predicted to be low, and
bioavailable silver is expected to be in ionic rather than particulate
form
Discovery of TetrahydropyrazoloÂpyridine as Sphingosine 1‑Phosphate Receptor 3 (S1P<sub>3</sub>)‑Sparing S1P<sub>1</sub> Agonists Active at Low Oral Doses
FTY720 is the first oral small molecule
approved for the treatment
of people suffering from relapsing–remitting multiple sclerosis.
It is a potent agonist of the S1P<sub>1</sub> receptor, but its lack
of selectivity against the S1P<sub>3</sub> receptor has been linked
to most of the cardiovascular side effects observed in the clinic.
These findings have triggered intensive efforts toward the identification
of a second generation of S1P<sub>3</sub>-sparing S1P<sub>1</sub> agonists.
We have recently disclosed a series of orally active tetrahydroisoquinoline
(THIQ) compounds matching these criteria. In this paper we describe
how we defined and implemented a strategy aiming at the discovery
of selective structurally distinct follow-up agonists. This effort
culminated with the identification of a series of orally active tetrahydropyrazoloÂpyridines