9 research outputs found
Environmental Photochemistry of Altrenogest: Photoisomerization to a Bioactive Product with Increased Environmental Persistence via Reversible Photohydration
Despite its wide use as a veterinary pharmaceutical, environmental fate data is lacking for altrenogest, a potent synthetic progestin. Here, it is reported that direct photolysis of altrenogest under environmentally relevant conditions was extremely efficient and rapid (half-life âŒ25 s). Photolysis rates (observed rate constant kobs = 2.7 ± 0.2 Ă 10â2 sâ1) were unaffected by changes in pH or temperature but were sensitive to oxygen concentrations (N2-saturated kobs = 9.10 ± 0.32 Ă 10â2 sâ1; O2-saturated kobs = 1.38 ± 0.11 Ă 10â2 sâ1). The primary photoproduct was identified as an isomer formed via an internal 2 + 2 cycloaddition reaction; the triplet lifetime (8.4 ± 0.2 ÎŒs) and rate constant (8 Ă 104 sâ1) of this reaction were measured using transient absorption spectroscopy. Subsequent characterization determined that this primary cycloaddition photoproduct undergoes photohydration. The resultant photostable secondary photoproducts are subject to thermal dehydration in dark conditions, leading to reversion to the primary cycloaddition photoproduct on a time scale of hours to days, with the photohydration and dehydration repeatable over several light/dark cycles. This dehydration reaction occurs more rapidly at higher temperatures and is also accelerated at both high and low pH values. In vitro androgen receptor (AR)-dependent gene transcriptional activation cell assays and in silico nuclear hormone receptor screening revealed that certain photoproducts retain significant androgenic activity, which has implications for exposure risks associated with the presence and cycling of altrenogest and its photoproducts in the environment.ISSN:0013-936XISSN:1520-585
Environmental Photochemistry of Altrenogest: Photoisomerization to a Bioactive Product with Increased Environmental Persistence via Reversible Photohydration
Despite
its wide use as a veterinary pharmaceutical, environmental
fate data is lacking for altrenogest, a potent synthetic progestin.
Here, it is reported that direct photolysis of altrenogest under environmentally
relevant conditions was extremely efficient and rapid (half-life âŒ25
s). Photolysis rates (observed rate constant <i>k</i><sub>obs</sub> = 2.7 ± 0.2 Ă 10<sup>â2</sup> s<sup>â1</sup>) were unaffected by changes in pH or temperature but were sensitive
to oxygen concentrations (N<sub>2</sub>-saturated <i>k</i><sub>obs</sub> = 9.10 ± 0.32 Ă 10<sup>â2</sup> s<sup>â1</sup>; O<sub>2</sub>-saturated <i>k</i><sub>obs</sub> = 1.38 ± 0.11 Ă 10<sup>â2</sup> s<sup>â1</sup>). The primary photoproduct was identified as an isomer formed via
an internal 2 + 2 cycloaddition reaction; the triplet lifetime (8.4
± 0.2 ÎŒs) and rate constant (8 Ă 10<sup>4</sup> s<sup>â1</sup>) of this reaction were measured using transient absorption
spectroscopy. Subsequent characterization determined that this primary
cycloaddition photoproduct undergoes photohydration. The resultant
photostable secondary photoproducts are subject to thermal dehydration
in dark conditions, leading to reversion to the primary cycloaddition
photoproduct on a time scale of hours to days, with the photohydration
and dehydration repeatable over several light/dark cycles. This dehydration
reaction occurs more rapidly at higher temperatures and is also accelerated
at both high and low pH values. In vitro androgen receptor (AR)-dependent
gene transcriptional activation cell assays and in silico nuclear
hormone receptor screening revealed that certain photoproducts retain
significant androgenic activity, which has implications for exposure
risks associated with the presence and cycling of altrenogest and
its photoproducts in the environment
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Test-retest resting-state fMRI in healthy elderly persons with a family history of Alzheimerâs disease
We present a test-retest dataset of resting-state fMRI data obtained in 80 cognitively normal elderly volunteers enrolled in the âPre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer's Diseaseâ (PREVENT-AD) Cohort. Subjects with a family history of Alzheimer's disease in first-degree relatives were recruited as part of an on-going double blind randomized clinical trial of Naproxen or placebo. Two pairs of scans were acquired ~3 months apart, allowing the assessment of both intra- and inter-session reliability, with the possible caveat of treatment effects as a source of inter-session variation. Using the NeuroImaging Analysis Kit (NIAK), we report on the standard quality of co-registration and motion parameters of the data, and assess their validity based on the spatial distribution of seed-based connectivity maps as well as intra- and inter-session reliability metrics in the default-mode network. This resource, released publicly as sample UM1 of the Consortium for Reliability and Reproducibility (CoRR), will benefit future studies focusing on the preclinical period preceding the appearance of dementia in Alzheimer's disease