Anti-fibrillogenic and fibril destabilizing effects of metal ions on cystatin fibrils

Metals such as Cu²⁺, Fe³⁺, and Zn²⁺ are major contributors to the biology of a brain in stages of health, aging, and disease because of their unique effects on both protein structures (misfolding) and oxidative stress. The relationship between metal ions and neurodegenerative diseases is very complicated. Our study highlights how metal ions influence amyloid formation at low pH and on preformed amyloid fibrils. By using thioflavin T assay, ANS fluorescence, Congo red assay, circular dichroism, and microscopy to elucidate the effects of Cu²⁺, Fe³⁺, and Zn²⁺ on goat brain cystatin (GBC) aggregation at low pH. Results showed that Cu²⁺ and Fe³⁺ inhibit fibril formation of GBC by promoting amorphous aggregates. However, Zn²⁺ exclusively promotes fibril formation at low pH, leading to the formation of more ordered aggregates. Furthermore, the combined results of these complementary methods also suggested that Cu²⁺ and Fe³⁺ destabilize the β-sheet secondary structure of preformed amyloid fibrils of GBC.     

Combination of dual-energy computed tomography and iterative metal artefact reduction to increase general quality of imaging for radiotherapy patients with high dense materials. Phantom study

PurposeTo evaluate the use of pseudo-monoenergetic reconstructions (PMR) from dual-energy computed tomography, combined with the iterative metal artefact reduction (iMAR) method.MethodsPseudo-monoenergetic CT images were obtained using the dual-energy mode on the Siemens Somatom Definition AS scanner. A range of PMR combinations (70–130 keV) were used with and without iMAR. A Virtual Water™ phantom was used for quantitative assessment of error in the presence of high density materials: titanium, alloys 330 and 600. The absolute values of CT number differences (AD) and normalised standard deviations (NSD) were calculated for different phantom positions. Image quality was assessed using an anthropomorphic pelvic phantom with an embedded hip prosthesis. Image quality was scored blindly by five observers.ResultsAD and NSD values revealed differences in CT number errors between tested sets. AD and NSD were reduced in the vicinity of metal for images with iMAR (p < 0.001 for AD/NSD). For ROIs away from metal, with and without iMAR, 70 keV PMR and pCT AD values were lower than for the other reconstructions (p = 0.039). Similarly, iMAR NSD values measured away from metal were lower for 130 keV and 70 keV PMR (p = 0.002). Image quality scores were higher for 70 keV and 130 keV PMR with iMAR (p = 0.034).ConclusionThe use of 70 keV PMR with iMAR allows for significant metal artefact reduction and low CT number errors observed in the vicinity of dense materials. It is therefore an attractive alternative to high keV imaging when imaging patients with metallic implants, especially in the context of radiotherapy planning.     

Do soft drinks affect metal ions release from orthodontic appliances?

ObjectiveThe effect of orange juice and Coca Cola^® on the release of metal ions from fixed orthodontic appliances.Materials and methodsA continuous flow system designed for in vitro testing of orthodontic appliances was used. Orange juice/Coca Cola^® was flowing through the system alternately with artificial saliva for 5.5 and 18.5 h, respectively. The collected samples underwent a multielemental ICP-OES analysis in order to determine the metal ions release pattern in time.ResultsThe total mass of ions released from the appliance into orange juice and Coca Cola^® (respectively) during the experiment was calculated (μg): Ni (15.33; 37.75), Cr (3.604; 1.052), Fe (48.42; ≥156.1), Cu (57.87, 32.91), Mn (9.164; 41.16), Mo (9.999; 30.12), and Cd (0.5967; 2.173).ConclusionsIt was found that orange juice did not intensify the release of metal ions from orthodontic appliances, whereas Coca Cola^® caused increased release of Ni ions.     

Effects of variations in soil water potential,depth of N placement,and cultivar on postanthesis N uptake by wheat

This study was conducted to investigate the influence of soil water potential, depth of N placement, timing, and cultivar on uptake of a small dose of labeled N applied after anthesis by wheat (Triticum aestivum L.) Understanding postanthesis N accumulation should allow better control of grain protein concentration through proper manipulation of inputs. Two hard, red spring-wheat cultivars were planted in early and late fall each yr of a 2-yr field experiment. Less than 1 kg N ha^–1 as K ¹⁵NO₃ was injected into the soil at two depths: shallow (0.05 to 0.08 m) and deep (0.15 to 0.18 m). In both years an irrigation was applied at anthesis, and injections of labeled N were timed 4, 12, and 20 days after anthesis (DAA). Soil water potential was estimated at the time of injection. Mean recovery of ¹⁵N in grain and straw was 57% of the ¹⁵N applied. Recovery did not differ between the high-protein (Yecora Rojo) and the low-protein (Anza or Yolo) cultivars. Mean recovery from deep placement was 60% versus only 54% from shallow placement (p < 0.01). Delaying the time of injection decreased mean recovery significantly from 58% at 4 DAA to 54% at 20 DAA. This decrease was most pronounced in the shallow placement, where soil drying was most severe. Regressions of recovery on soil water potential of individual cultivar x yr x planting x depth treatments were significant only under the driest conditions. Stepwise regression of ¹⁵N recovery on soil water potential and yield parameters using data from all treatments of both years resulted in an equation including soil water potential and N yield, with a multiple correlation coefficient of 0.64. The translocation of ¹⁵N to grain was higher (0.89) than the nitrogen harvest index (0.69), and showed a highly significant increase with increase in DAA. This experiment indicates that the N uptake capacity of wheat remains reasonably constant between 4 and 20 DAA unless soil drying is severe.     

Multifunctional liposomes for nasal delivery of the anti-Alzheimer drug tacrine hydrochloride

The purpose of this study was the development of multifunctional liposomes for nasal administration of tacrine hydrochloride. Liposomes were prepared using traditional excipients (cholesterol and phosphatidylcholine), partly enriched with α-tocopherol and/or Omega3 fatty acids. This approach was chosen in order to obtain at the same time two positive results: an enhanced drug permeation through nasal mucosa and a concomitant neuroprotective effect. Several liposome formulations were prepared using the Reverse Phase Evaporation technique followed by membrane filter extrusion. In particular, liposome capacity to enhance drug permeation was evaluated by means of membrane permeation and cellular uptake studies. Furthermore, liposome effect on neuronal viability and intracellular ROS production was evaluated as well as their cytoprotective effect against oxidative stress. All liposome formulations showed a mean diameter in the range of 175?nm to 219?nm with polydispersity index lower than 0.22, a lightly negative zeta potential and excellent encapsulation efficiency. Moreover, along with good mucoadhesive properties, multifunctional liposomes showed a markedly increase in tacrine permeability, which can be related to liposome fusion with cellular membrane, a hypothesis, which was also supported by cellular uptake studies. Finally, the addition of α-tocopherol without Omega3 fatty acids, was found to increase the neuroprotective activity and antioxidant properties of liposomes.     

HSP70 induction by bleomycin metal core analogs

Induction of heat shock protein 70 (HSP70) is known to be effective against various diseases. We are interested in HSP70 induction capability of an antitumor antibiotic bleomycin which produces oxidative stress by iron chelate formation and oxygen activation in a cell. The HSP70 induction activity of bleomycin and its six metal core analogs was examined, and a compound HPH-1Trt of 10 μM was found to induce this protein in a pheochromocytoma cell line and some T cell and monocytic cell lines. Its mechanism is increase of HSP70 mRNA, but higher concentration of this compound showed toxicity. Two new derivatives were then synthesized, and one of them named DHPH-1Trt was shown to have less toxicity and higher HSP70 induction activity. This study would lead to a clue for new HSP70 inducer clinically used in near future.     

Dynamics of concentrations and nutrient fluxes in the xylem of Ricinus communis– diurnal course, impact of nutrient availability and nutrient uptake

Diurnal courses of nutrient transport in the xylem and their response to external availability of nutrients were studied. In soil culture, maximal concentrations in all analysed substances were observed during night‐time. Over experimental periods of up to 20 d, concentrations of some ions increased, most by accumulation in the soil. Stringent nutrient conditions were established in a novel pressure chamber. An aeroponic nutrient delivery system inside allows the sampling of xylem sap from intact plants under full control of the nutrient conditions at the root. Analysis of xylem transport under these highly defined conditions established that (1) diurnal variations in concentrations and fluxes in the xylem are dominated by plant‐internal processes; (2) concentrations of nutrients in the xylem sap are highly but specifically correlated with each other; (3) nitrate uptake and nitrate flux to the shoot are largely uncoupled; and (4) in continuous light, diurnal variations of xylem sap concentrations vanish. Step changes in nitrate concentrations of the nutrient solution established that (5) the concomitant increase in nitrate concentration and flux in the xylem is delayed by 2–3 h and is only transient. Diurnal variations of xylem sap composition and use of the new technique to elucidate xylem‐transport mechanisms are discussed.     

Synthesis of alkali metal hexahydroaluminate complexes using dimethyl ether as a reaction medium

A novel method of preparation of hexahydroaluminate complexes M₃AlH₆ (M = Li, Na or K) from the corresponding alkali metal hydride and tetrahydroaluminate has been explored, using dimethyl ether (Me₂O) as a solvent at near-ambient temperatures. The results are compared with those obtained using a recently established mechanochemical approach. Characterization of the products by powder X-ray diffraction revealed M₃AlH₆ to be formed in high yield for M = Li and Na, but not for M = K. The attempted preparation of Li₂NaAlH₆ and Li₂KAlH₆ was unsuccessful.     

The accumulation of heavy metals in Typha latifolia L. grown in a stream carrying secondary effluent

Typha latifolia L. from aquatic plants is widely found throughout Kehli Stream (Elazig, Turkey). This study examined the uptake of some metals by T. latifolia and the transfer from roots to other plant parts. The accumulation of Mn in T. latifolia L. can be suggested as a tolerance strategy due to its transfer factor higher than 1.0. The enrichment coefficients in the leaves of T. latifolia L. were higher than 1.0 for Zn and Mn and often lower than 1.0 for other metals. Similarly, the enrichment coefficients of all metals, except for Cr, in roots of T. latifolia L. were higher than 1.0. This study demonstrated that T. latifolia L. could be considered as either a bio-indicator or a bio-accumulator for sediments and water polluted by metals.