Baseline distribution of stable copper isotope compositions of the brain and other organs in mice.

Copper (Cu) stable isotopes are useful for understanding pathways and tracing changes in Cu homeostasis, such as those induced by various diseases (e.g. liver cirrhosis, numerous forms of cancer, and neurodegenerative diseases). However, this utility relies on a baseline understanding of the natural distribution of Cu isotopes between organs of healthy organisms, which is not well-known at present. Here, the distribution of natural Cu isotopes in the brain, liver, red blood cells, plasma, kidneys, and muscle of 14 mice (7 males and 7 females) from three different genetic backgrounds is assessed. We show that the Cu isotopic composition of most mouse organs is isotopically distinct from one another. The most striking feature is the heavy isotope enrichment of the kidney (δ65Cu = 1.65 ± 0.06‰, 2SE), brain (δ65Cu = 0.87 ± 0.03‰, 2SE) and liver (δ65Cu = 0.71 ± 0.24‰, 2SE) compared to blood components, i.e. red blood cells (RBCs) (δ65Cu = 0.30 ± 0.06‰, 2SE), and plasma (δ65Cu = -0.61 ± 0.08‰, 2SE), with δ65Cu being the per mil deviation of the 65Cu/63Cu ratio from the NIST SRM 976 standard. Differences in genetic background do not appear to affect the isotopic distribution of Cu. Interestingly, male and female mice appear to have different Cu concentrations and isotopic compositions in their brain, plasma, muscle, and RBC. By demonstrating that organs have distinct isotopic compositions, our study reinforces the notion that Cu stable isotopes can be used to trace changes in homeostasis in diseases affecting Cu distribution, such as Alzheimer's disease, liver cancer, and possible chronic kidney failure.

Zn Isotope Fractionation during Sorption onto Kaolinite.

In this study, we quantify zinc isotope fractionation during its sorption onto kaolinite, by performing experiments under various pH, ionic strength, and total Zn concentrations. A systematic enrichment in heavy Zn isotopes on the surface of kaolinite was measured, with Δ(66)Znadsorbed-solution ranging from 0.11‰ at low pH and low ionic strength to 0.49‰ at high pH and high ionic strength. Both the measured Zn concentration and its isotopic ratio are correctly described using a thermodynamic sorption model that considers two binding sites: external basal surfaces and edge sites. Based on this modeling approach, two distinct Zn isotopic fractionation factors were calculated: Δ(66)Znadsorbed-solution = 0.18 ± 0.06‰ for ion exchange onto basal sites, and Δ(66)Znadsorbed-solution = 0.49 ± 0.06‰ for specific complexation onto edge sites. These two distinct factors indicate that Zn isotope fractionation is dominantly controlled by the chemical composition of the solution (pH, ionic strength).

Transient signal isotope analysis: validation of the method for isotope signal synchronization with the determination of amplifier first-order time constants.

RATIONALE: During transient signal acquisition by Multi-Collection Inductively Coupled Plasma Mass Spectrometry (MC-ICPMS), an isotope ratio increase or decrease (isotopic drift hereafter) is often observed which is related to the different time responses of the amplifiers involved in multi-collection. This isotopic drift affects the quality of the isotopic data and, in a recent study, a method of internal amplifier signal synchronization for isotope drift correction was proposed. In this work the determination of the amplifier time constants was investigated in order to validate the method of internal amplifier signal synchronization for isotope ratio drift correction. METHODS: Two different MC-ICPMS instruments, the Neptune and the Neptune Plus, were used, and both the lead transient signals and the signal decay curves of the amplifiers were investigated. RESULTS: Our results show that the first part of the amplifier signal decay curve is characterized by a pure exponential decay. This part of the signal decay was used for the effective calculation of the amplifier first-order time constants. The small differences between these time constants were compared with time lag values obtained from the method of isotope signal synchronization and were found to be in good agreement. CONCLUSIONS: This work proposes a way of determining amplifier first-order time constants. We show that isotopic drift is directly related to the amplifier first-order time constants and the method of internal amplifier signal synchronization for isotope ratio drift correction is validated.

Photoreactivity of indirubin derivatives.

Twenty-nine analogs of indirubin, an isomer of indigo, have been synthesized to optimize its promising kinase inhibitory scaffold. These compounds being also pigmented, have been tested for their photoreactivity. Absorption maxima were between 485 nm and 560 nm. Addition of fetal calf serum induced fluorescence and time dependent absorption modifications. Appropriate illumination induced Reactive Oxygen Species (ROS) production for nineteen compounds out of twenty-nine. The relationship between fluorescence and ROS production is discussed. Six compounds showed an important toxicity on F98 cells, a murine glioma cell line. Three of these were found to be also phototoxic, as four other non-toxic compounds. All but one phototoxic compounds were detected as ROS producers by in vitro tests. Photoreactivity assessment is important to anticipate adverse reactions for compounds that might be clinically developed. The experimental assay was found to be the only way to evaluate the photoreactivity of this family of compounds since no predictive criteria on structures could be found. Combining the vascular tumor growth inhibition induced by kinase inhibitors with the massive local blood flow arrest following photodynamic treatment may be an efficient anti-cancer strategy. These data could orientate further syntheses of either non-photoreactive compounds or compounds displaying both kinase inhibitory activity and strong phototoxicity.