The Iron Chelator Deferiprone Improves the Phenotype in a Mouse Model of Tauopathy1

2020 ◽  
Vol 77 (2) ◽  
pp. 753-771 ◽  
Author(s):  
Shalini S. Rao ◽  
Stuart. D. Portbury ◽  
Larissa Lago ◽  
Ashley I. Bush ◽  
Paul A. Adlard

Background: Abnormally hyperphosphorylated tau is a defining pathological feature of tauopathies, such as Alzheimer’s disease (AD), and accumulating evidence suggests a role for iron in mediating tau pathology that may lead to cognitive decline in these conditions. The metal chelator deferiprone (DFP), which has a high affinity for iron, is currently in clinical trials for AD and Parkinson’s disease. However, the effect of DFP on tau pathology remains underexplored. Objective: We aimed to investigate the impact of chronic DFP treatment on tau pathology using a well-characterized mouse model of tauopathy (rTg(tauP301L)4510). Methods: Animals were treated daily with DFP (100 mg/kg) via oral gavage for 16 weeks. After 14 weeks, mice were tested in the Y-maze, open field, Morris water maze, and rotorod. At the end of the study, brain tissue was collected to examine metal levels (using inductively coupled plasma-mass spectrometry) and for western blot analysis of DFP on tau and iron associated pathways. Results: DFP significantly reduced anxiety-like behavior, and revealed a trend toward improved cognitive function. This was accompanied by a decrease in brain iron levels and sarkosyl-insoluble tau. Our data also showed downregulation of the tau kinases glycogen synthase kinase 3β and cyclin dependent kinase-5 in DFP treated mice and an increase in the methylation of the catalytic subunit of protein phosphatase 2A. Conclusion: These data support the hypothesis that suggests that iron plays a neurotoxic role in tauopathies and may be a potential therapeutic target for this class of disorders.

Author(s):  
Inna Yu. Tarmaeva ◽  
Anatoliy V. Skalny ◽  
Olga G. Bogdanova ◽  
Andrey R. Grabeklis ◽  
Alexandr I. Belykh

Introduction.The study of the elemental status of the population of individual regions of the Russian Federation with the purpose of scientific development and implementation of measures for elimination of revealed elementosis is a promising direction for preventive medicine.The aim of the studyis to study the elemental status of the adult able-bodied population of the Republic of Buryatia, which was part of the Siberian Federal district (SFD) until 2018.Materials and methods.The analysis was performed by inductively coupled plasma mass spectrometry (ICP-MS) on the basis of the accredited laboratory of “Center of biotic medicine”. (Moscow; ISO 9001: 2008 certificate 54Q10077 from 21.05.2010). The content of chemical elements in the hair of 130 adults (102 women and 28 men) aged 25–50 years was studied. This indicator serves as an indicator in assessing the impact of the environment on the human body. Methods of nonparametric statistics were used for mathematical processing of the data.Results.For women living in the Republic of Buryatia, the maximum values of Zn, increased levels of Cu, Li, Si were revealed; for men — the maximum values of Mg, Cr, Si, increased levels of P, Li, Se, V, Pb. Minimum values were found for P, Fe, V. Elemental status indicates a significant degree of prevalence of essential trace element deficiencies and electrolyte imbalance. The obtained data can be used as reference values for the content of chemical elements in the hair of adults living in the Republic of Buryatia.Conclusions:Elemental analysis of the population of the Republic of Buryatia indicates imbalances among the adult working-age population.


2013 ◽  
Vol 20 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Hüseyin Altundağ ◽  
Mustafa Şahin Dündar ◽  
Can Serkan Keskin

Abstract The availability of Cd, Co, Cr, Cu, Mn, Ni, Pb, Fe and Zn of dust from vehicle air and pollen filters were investigated by four-step BCR (European Community Bureau of Reference) sequential extraction procedure. The acid-soluble, reducible, oxidizable, residual extracts were measured by inductively coupled plasma-optical emission spectrometry (ICP-OES). The results indicated that both of air and pollen filter dusts contained higher concentration of Fe. To estimate the accuracy of the method the standard reference material BCR 701 was used. The results for recovery all the elements were found in the range 95.4-101.3%. The mean concentrations [μg/g] of trace elements in dusts from air filters/pollen filters were: cadmium 16.72/17.56; cobalt 24.22/23.72; chromium 46.02/55.44; copper 44.92/37.67; iron 1868.03/1854.92; manganese 231.2/213.64; nickel 38.89/45.27; lead 60.99/67.17; zinc 199.58/201.25. The results obtained are in agreement with data reported in the literature.


2009 ◽  
Vol 06 (12) ◽  
pp. 7-14
Author(s):  
Josiane LOYOLA ◽  
Simone Lorena QUITERIO ◽  
Viviane ESCALEIRA ◽  
Graciela ARBILLA

The petroleum industry has difficulties to assess the trace metal content in liquid fuels. In this work, it is proposed to solve this problem determining these metals by collecting particulate matter atmospheric samples and analysing their metal content. Samples of total particulate matter and of inhalable particles (PM10) were collected in a bus station in the period August 2006-February 2007. The only significant emission source in that location are the buses, fueled by diesel, since light duty vehicles account for about 1-2% of the total vehicular flux and no other activities are developed in the area. Metal levels were determined by ICP-OES (Inductively Coupled Plasma Optical Emission Spectroscopy). Ca, Mg, Fe and Al were the most abundant compounds, and account for about 50.1%, 24.2%, 6.5% and 18.7%, respectively, of the metal contain. Co, Ni, Cd, Cr and Pb were under their detection limits, except for a few samples. Ca, Mg, Zn and Cu were determined in higher ratios that those currently find in crustal materials indicating that these elements may have important combustion sources and are enriched in the soil.


Nanomaterials ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2562
Author(s):  
Pierre-Marie Coulon ◽  
Peng Feng ◽  
Tao Wang ◽  
Philip A. Shields

The formation of gallium nitride (GaN) semi-polar and non-polar nanostructures is of importance for improving light extraction/absorption of optoelectronic devices, creating optical resonant cavities or reducing the defect density. However, very limited studies of nanotexturing via dry etching have been performed, in comparison to wet etching. In this paper, we investigate the formation and morphology of semi-polar (112¯2) and non-polar (112¯0) GaN nanorods using inductively coupled plasma (ICP) etching. The impact of gas chemistry, pressure, temperature, radio-frequency (RF) and ICP power and time are explored. A dominant chemical component is found to have a significant impact on the morphology, being impacted by the polarity of the planes. In contrast, increasing the physical component enables the impact of crystal orientation to be minimized to achieve a circular nanorod profile with inclined sidewalls. These conditions were obtained for a small percentage of chlorine (Cl2) within the Cl2 + argon (Ar) plasma combined with a low pressure. Damage to the crystal was reduced by lowering the direct current (DC) bias through a reduction of the RF power and an increase of the ICP power.


2019 ◽  
Vol 16 (18) ◽  
pp. 3565-3582 ◽  
Author(s):  
Nicolai Schleinkofer ◽  
Jacek Raddatz ◽  
André Freiwald ◽  
David Evans ◽  
Lydia Beuck ◽  
...  

Abstract. Here we present a comprehensive attempt to correlate aragonitic Na∕Ca ratios from Desmophyllum pertusum (formerly known as Lophelia pertusa), Madrepora oculata and a caryophylliid cold-water coral (CWC) species with different seawater parameters such as temperature, salinity and pH. Living CWC specimens were collected from 16 different locations and analyzed for their Na∕Ca ratios using solution-based inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements. The results reveal no apparent correlation with salinity (30.1–40.57 g kg−1) but a significant inverse correlation with temperature (-0.31±0.04 mmolmol-1∘C-1). Other marine aragonitic organisms such as Mytilus edulis (inner aragonitic shell portion) and Porites sp. exhibit similar results highlighting the consistency of the calculated CWC regressions. Corresponding Na∕Mg ratios show a similar temperature sensitivity to Na∕Ca ratios, but the combination of two ratios appears to reduce the impact of vital effects and domain-dependent geochemical variation. The high degree of scatter and elemental heterogeneities between the different skeletal features in both Na∕Ca and Na∕Mg, however, limit the use of these ratios as a proxy and/or make a high number of samples necessary. Additionally, we explore two models to explain the observed temperature sensitivity of Na∕Ca ratios for an open and semi-enclosed calcifying space based on temperature-sensitive Na- and Ca-pumping enzymes and transport proteins that change the composition of the calcifying fluid and consequently the skeletal Na∕Ca ratio.


2010 ◽  
Vol 56 (No. 5) ◽  
pp. 244-251 ◽  
Author(s):  
K. Agyarko ◽  
E. Darteh ◽  
B. Berlinger

Concentrations of Cd, Hg, Pb, Cr, Fe, Co, Ni, Cu, Zn, Mo and As were determined in soils and leaves of plants from refuse dumpsites and background soils in two cities, a municipality and a rural community in Ghana, using a ThermoFinnigan Element 2 high resolution inductively coupled plasma mass spectrometric (HR-ICP-MS) instrument. The refuse dump soils were classified between 'Uncontaminated to Moderate' and 'Strongly Contaminated'. Pollution levels for Cd (Igeo = 2.06–2.40) and Zn (Igeo = 2.95–3.36) were higher than of the other metals. The refuse dump soil from the rural community was the least polluted with the metals. Fe and Ni loads in plants from the refuse dump soils in the cities and the municipality were beyond the normal ranges of 40–500 µg/g (Fe) and 0.02–5.00 µg/g (Ni). Transfer ratios for Cd, Hg, Cu, Zn and Pb and Fe of plants from the background soils were higher than those from the refuse dump soils, which might be due to the higher levels of organic matter, pH, phosphate, Ca and Mg in the refuse dump soils.


2020 ◽  
Vol 36 (4) ◽  
pp. 272-286
Author(s):  
Nahla Kamal ◽  
AH Zaki ◽  
Ahmed AG El-Shahawy ◽  
Ossama M Sayed ◽  
SI El-Dek

The present research investigated the impact of the morphology change of titanate (TiO2) nanostructures on its tissue distribution and toxicity. The TiO2 nanotubes, rods, and ribbons were synthesized by the hydrothermal technique, and the morphology was adjusted by alteration of the hydrothermal duration time. The characterization techniques were X-ray diffraction, high-resolution transmission electron microscopy, dynamic light scattering, and the Brunauer–Emmett–Teller method for measuring the surface area. The intravenously administrated dose (5 mg/kg) was injected as a single dose for 1 day and consecutively for 42 days. The quantitative analysis of accumulated TiO2 nanostructures in the liver, spleen, and the heart was performed using an inductively coupled plasma emission spectrometer, and the organs’ toxicity was estimated by histopathological analysis. The prepared nanostructures exhibited differences in morphology, crystallinity, size distribution, surface area, zeta potential, and aspect ratio. The results revealed a tissue distribution difference between the liver, spleen, and heart of these nanostructures, the distribution order was the liver, spleen, and the heart for all TiO2 nanostructures. The toxicity was induced with different degrees. The nanotubes were the most harmful among the three formats. In summary, changes in the morphology of the TiO2 nanostructures change its distribution and toxicity.


2013 ◽  
Vol 740-742 ◽  
pp. 825-828 ◽  
Author(s):  
Jerome Biscarrat ◽  
Jean François Michaud ◽  
Emmanuel Collard ◽  
Daniel Alquier

Due to its inert chemical nature, plasma etching is the most effective technique to pattern SiC. In this paper, dry etching of 4H-SiC substrate in Inductively Coupled Plasma (ICP) has been studied in order to evaluate the impact of process parameters on the characteristics of etching such as etch rate and trenching effect. Key process parameters such as platen power and ICP coil power prove to be essential to control the SiC etch rate. On the other hand, the ICP coil power and the working pressure mainly master the trenching effect. Our results enlighten that high etch rate with minimal trenching effect can be obtained using high ICP coil power and low working pressure.


2020 ◽  
Vol 83 (6) ◽  
pp. 935-942
Author(s):  
LOAN THI THANH CAO ◽  
LESLIE D. BOURQUIN

ABSTRACT Historically, lead arsenate pesticides were commonly used in fruit orchards. Residues of metals from this historical use can persist in soil for decades, which can result in potential risk for humans if they consume fruits grown on contaminated soil. This research was conducted to assess lead and arsenic levels in apples, leaves, and orchard soil where the apples were grown to determine the relationship between metal levels in fruits and fruit products with those in orchard soil. Soil and tree tissue samples were collected from several Michigan farms, and metal concentrations were quantified by using microwave extraction and inductively coupled plasma mass spectrometry. Soil samples were collected at depths of 0 to 20 cm and 20 to 40 cm at a distance of 1 m from the tree trunk. Fruit samples also were processed into juice and pomace fractions to assess the partitioning of arsenic and lead during juice processing. The lead concentration was significantly higher in topsoil (9.4 μg/kg) compared with subsoil (6.9 μg/kg), but the arsenic content did not differ between the two soil layers (P > 0.05). Lead concentrations in apple leaves were correlated with lead in topsoil (0 to 20 cm; P = 0.03). Concentrations of total arsenic in all juice samples were less than 1 μg/kg and showed less potential than lead for uptake and translocation to fruits. There was no significant relationship between soil arsenic content and total arsenic concentrations in juice, pomace, and leaf samples (P > 0.05). Results of this research indicate that lead and total arsenic concentrations in apples and apple products from these selected orchards in Michigan are unlikely to be impacted by the contamination of these metals in orchard soil. HIGHLIGHTS


Sign in / Sign up

Export Citation Format

Share Document