No Benefit from Chronic Lithium Dosing in a Sibling-Matched, Gender Balanced, Investigator-Blinded Trial Using a Standard Mouse Model of Familial ALS

Background: In any animal model of human disease a positive control therapy that demonstrates efficacy in both the animal model and the human disease can validate the application of that animal model to the discovery of new therapeutics. Such a therapy has recently been reported by Fornai et al. using chronic lithium carbonate treatment and showing therapeutic efficacy in both the high-copy SOD1G93A mouse model of familial amyotrophic lateral sclerosis (ALS), and in human ALS patients. Methodology/Principal Findings: Seeking to verify this positive control therapy, we tested chronic lithium dosing in a sibling-matched, gender balanced, investigator-blinded trial using the high-copy (average 23 copies) SOD1G93A mouse (n = 27–28/group). Lithium-treated mice received single daily 36.9 mg/kg i.p. injections from 50 days of age through death. This dose delivered 1 mEq/kg (6.94 mg/kg/day lithium ions). Neurological disease severity score and body weight were determined daily during the dosing period. Age at onset of definitive disease and survival duration were recorded. Summary measures from individual body weight changes and neurological score progression, age at disease onset, and age at death were compared using Kaplan-Meier and Cox proportional hazards analysis. Our study did not show lithium efficacy by any measure. Conclusions/Significance: Rigorous survival study design that includes sibling matching, gender balancing, investigato

Optical Drug Monitoring: Photoacoustic Imaging of Nanosensors to Monitor Therapeutic Lithium in Vivo

Personalized medicine could revolutionize how primary care physicians treat chronic disease and how researchers study fundamental biological questions. To realize this goal, we need to develop more robust, modular tools and imaging approaches for in vivo monitoring of analytes. In this report, we demonstrate that synthetic nanosensors can measure physiologic parameters with photoacoustic contrast, and we apply that platform to continuously track lithium levels in vivo. Photoacoustic imaging achieves imaging depths that are unattainable with fluorescence or multiphoton microscopy. We validated the photoacoustic results that illustrate the superior imaging depth and quality of photoacoustic imaging with optical measurements. This powerful combination of techniques will unlock the ability to measure analyte changes in deep tissue and will open up photoacoustic imaging as a diagnostic tool for continuous physiological tracking of a wide range of analytes

Rheological, physicochemical, and microstructural properties of asphalt binder modified by fumed silica nanoparticles

Warm mix asphalt (WMA) is gaining increased attention in the asphalt paving industry as an eco-friendly and sustainable technology. WMA technologies are favorable in producing asphalt mixtures at temperatures 20–60 °C lower in comparison to conventional hot mix asphalt. This saves non-renewable fossil fuels, reduces energy consumption, and minimizes vapors and greenhouse gas emissions in the production, placement and conservation processes of asphalt mixtures. At the same time, this temperature reduction must not reduce the performance of asphalt pavements in-field. Low aging resistance, high moisture susceptibility, and low durability are generally seen as substantial drawbacks of WMA, which can lead to inferior pavement performance, and increased maintenance costs. This is partly due to the fact that low production temperature may increase the amount of water molecules trapped in the asphalt mixture. As a potential remedy, here we use fumed silica nanoparticles (FSN) have shown excellent potential in enhancing moisture and aging susceptibility of asphalt binders. In this study, asphalt binder modification by means of FSN was investigated, considering the effects of short-term and long-term aging on the rheological, thermal, and microstructural binder properties. This research paves the way for optimizing WMA by nanoparticles to present enhanced green asphalt technology

The effects of subchronic lithium administration in male Wistar mice on some biochemical parameters

Lithium salts are efficiently used for treatment of psychiatric disorders. However, prolonged treatment frequently involves adverse side-effects. In the present work, effects of lithium carbonate administration on some biochemical parameters were studied in male mice. Lithium carbonate (20, 40 or 80 mg/kg body weight, corresponding to 3.77, 7.54 or 15.08 mg Li element/kg body weight, respectively) was injected daily for 14 or 28 days. The following parameters were recorded: water consumption, body weight, lithium and testosterone serum concentrations, activities of catalase (CAT), superoxide-dismutase (SOD) and glutathione-peroxidase (GPX) and level of lipid peroxidation (expressed as TBARS) in liver was performed. Lithium treatment, especially at the highest dose for 28 days, was found to induce weight gain, polydipsia and a significant decrease of plasma testosterone level. Lipid peroxidation level and activities of SOD and GPX were increased in liver which suggests a perturbation of the antioxidative status. Our results indicate that subchronic exposure to lithium, which induces weight gain and polydipsia under our experimental conditions, also damages the male reproductive system and triggers an oxidative stress in the liver