Chronic and pulse exposure effects of silver nanoparticles on natural lake phytoplankton and zooplankton.

The increasing use of silver nanoparticles (AgNPs) in consumer products raises concerns regarding the environmental exposure and impact of AgNPs on natural aquatic environments. Here, we investigated the effects of environmentally relevant AgNP concentrations on the natural plankton communities using in situ enclosures. Using twelve lake enclosures, we tested the hypotheses that AgNP concentration, dosing regimen, and capping agent (poly-vinyl pyrrolidone (PVP) vs. citrate) exhibit differential effects on plankton communities. Each of the following six treatments was replicated twice: control (no AgNPs added), low, medium, and high chronic PVP treatments (PVP-capped AgNPs added continuously, with target nominal concentrations of 4, 16, and 64 µg/L, respectively), citrate treatment (citrate-capped AgNPs added continuously, target nominal concentrations of 64 µg/L), and pulse treatment (64 µg/L PVP-AgNPs added as a single dose). Although Ag accumulated in the phytoplankton, no statistically significant treatment effect was found on phytoplankton community structure or biomass. In contrast, as AgNP exposure rate increased, zooplankton abundance generally increased while biomass and species richness declined. We also observed a shift in the size structure of zooplankton communities in the chronic AgNP treatments. In the pulse treatments, zooplankton abundance and biomass were reduced suggesting short periods of high AgNP concentrations affect zooplankton communities differently than chronic exposures. We found no evidence that capping agent affected AgNP toxicity on either community. Overall, our study demonstrates variable AgNP toxicity between trophic levels with stronger AgNP effects on zooplankton. Such effects on zooplankton are troubling and indicate that AgNP contamination could affect aquatic food webs.

Structure-activity relationship of a series of non peptidic RGD integrin antagonists targeting α5ß1: part 1.

Potent antagonists of the integrin α(5)ß(1), which are RGD mimetics built from tyrosine are described. This letter describes the optimization of in vitro potency obtained by variation of two parts of the molecule, the basic group and the linker between the basic group and the phenyl central core.

Structure-activity relationship of a series of non peptidic RGD integrin antagonists targeting α5ß1: part 2.

Potent antagonists of the integrin α(5)ß(1), which are RGD mimetics built from tyrosine are described. This paper describes the optimization of in vitro potency obtained by variation of two parts of the molecule, the central aromatic core and the amide moiety.

Pramipexole: augmentation in the treatment of depressive symptoms.

We describe a retrospective case series of three patients, two with bipolar depression and one with unipolar depression. Pramipexole is a Food and Drug Administration-approved antiparkinsonian agent, which, when used to augment antidepressants, would be considered an off-label use and should be discussed with the patient. These patients had robust responses to pramipexole augmentation of their treatment regimen. All three patients had been taking an atypical antipsychotic. The depressive symptoms were evaluated using the Hamilton Rating Scale for Depression.

Novel 4-anilinoquinazolines with C-6 carbon-linked side chains: synthesis and structure-activity relationship of a series of potent, orally active, EGF receptor tyrosine kinase inhibitors.

The structure-activity relationship of a novel subseries of 4-anilinoquinazoline EGFR inhibitors substituted at the C-6 position with carbon-linked side chains has been investigated. This exploration has led to the discovery of novel aminomethyl carboxamides with good biological, pharmacokinetic and physical properties.