Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress

Background: Methotrexate (MTX) is an antimetabolite broadly used in treatment of cancer and autoimmune diseases. MTX-induced hepatotoxicity limits its application. We investigated hepatoprotective effects of turmeric in MTX-induced liver toxicity. Methods: All experiments were performed on male Wistar albino rats that were randomly divided into six groups. Group one received saline orally for 30 days (control group), groups two and three received turmeric extract (100, 200 mg/kg respectively) orally for 30 days, group four received single dose, of MTX IP at day 30, groups five and six received turmeric extract 100 and 200 mg/kg orally respectively for 30 days and single dose of methoterxate IP (20 mg/kg) at day 30. Four days after MTX injection animals were sacrificed and evaluated. Blood ALT and AST (indicators of hepatocyte injury), ALP and bilirubin (markers of biliary function), albumin (reflect liver synthetic function) as well as the plasma TAS concentration (antioxidant defenses) were determined. The cellular antioxidant defense activities were examined in liver tissue samples using SOD, CAT, and GSH-Px for the oxidative stress, and MDA for lipid peroxidation. In addition, liver damage was evaluated histopathologically. Results: MTX significantly induced liver damage (P less than 0.05) and decreased its antioxidant capacity, while turmeric was hepatoprotective. Liver tissue microscopic evaluation showed that MTX treatment induced severe centrilobular and periportal degeneration, hyperemia of portal vein, increased artery inflammatory cells infiltration and necrosis, while all of histopathological changes were attenuated by turmeric (200 mg/kg). Conclusion: Turmeric extract can successfully attenuate MTX-hepatotoxicity. The effect is partly mediated through extracts antinflammatory activity.Funding Agencies|University of Manitoba start-up fund; Linkoping University; IGEN; Cancerfonden [2013/391]; VR-NanoVision [K2012-99X-22325-01-5]</p

Investigation of deuterium trapping and release in the JET divertor during the third ILW campaign using TDS

Selected set of samples from JET ITER-Like Wall (JET-ILW) divertor tiles exposed in 2015-2016 has been analysed using Thermal Desorption Spectrometry (TDS). The deuterium (D) amounts obtained with TDS were compared with Nuclear Reaction Analysis (NRA). The highest amount of D was found on the top part of inner divertor which has regions with the thickest deposited layers as for divertor tiles removed in 2014. This area resides deep in the scrape-off layer and plasma configurations for the second (ILW-2, 2013-2014) and the third (ILW-3, 2015-2016) JET-ILW campaigns were similar. Agreement between TDS and NRA is good on the apron of Tile 1 and on the upper vertical region whereas on the lower vertical region of Tile 1 the NRA results are clearly smaller than the TDS results. Inner divertor Tile 3 has somewhat less D than Tiles 0 and 1, and the D amount decreases towards the lower part of the tile. The D retention at the divertor inner and outer corner regions is not symmetric as there is more D retention poloidally at the inner than at the outer divertor corner. In most cases the TDS spectra for the ILW-3 samples are different from the corresponding ILW-2 spectra because HD and D-2 release occurs at higher temperatures than from the ILW-2 samples indicating that the low energy traps have been emptied during the plasma operations and that D is either in the energetically deep traps or located deeper in the sample

Investigation of deuterium trapping and release in the JET ITER-like wall divertor using TDS and TMAP

Selected set of samples from JET ITER-Like Wall (JET-ILW) divertor tiles exposed both in 2013-2014 and 2011-2014 has been analysed using Thermal Desorption Spectrometry (TDS). The deuterium (D) amounts obtained with TDS were compared with Ion Beam Analysis (IBA) and Secondary Ion Mass Spectrometry (SIMS) data. The highest amount of D was found on the top part of inner divertor which has regions with the thickest deposited layers. This area resides deep in the scrape-off layer. Changes in plasma configurations between the first (2011-2012) and the second (2013-2014) JET-ILW campaign altered the material migration towards the inner and the outer divertor corner increasing the amount of deposition in the shadowed areas of the divertor base tiles. D retention on the outer divertor tiles is clearly smaller than on the inner divertor tiles. Experimental TDS spectra for samples from the top part of inner divertor and from the outer strike point region were modelled using TMAP program. Experimental deuterium profiles obtained with SIMS have been used and the detrapping and the activation energies have been adjusted. Analysis of the results of the TMAP simulations enabled to determine the nature of traps in different samples

Deposition of impurity metals during campaigns with the JET ITER-like Wall

Post mortem analysis shows that mid and high atomic number metallic impurities are present in deposits on JET plasma facing components with the highest amount of Ni and W, and therefore the largest sink, being found at the top of the inner divertor. Sources are defined as "continuous" or "specific", in that "continuous" sources arise from ongoing erosion from plasma facing surfaces and "specific" are linked with specific events which decrease over time until they no longer act as a source. This contribution evaluates the sinks and estimates sources, and the balance gives an indication of the dominating processes. Charge exchange neutral erosion is found to be the main source of nickel, whereas erosion of divertor plasma facing components is the main source of tungsten. Specific sources are shown to have little influence over the global mid- and high-Z impurity concentrations in deposits

Erosion, screening, and migration of tungsten in the JET divertor

The erosion of tungsten (W), induced by the bombardment of plasma and impurity particles, determines the lifetime of plasma-facing components as well as impacting on plasma performance by the influx of W into the confined region. The screening of W by the divertor and the transport of W in the plasma determines largely the W content in the plasma core, but the W source strength itself has a vital impact on this process. The JET tokamak experiment provides access to a large set of W erosion-determining parameters and permits a detailed description of the W source in the divertor closest to the ITER one: (i) effective sputtering yields and fluxes as function of impact energy of intrinsic (Be, C) and extrinsic (Ne, N) impurities as well as hydrogenic isotopes (H, D) are determined and predictions for the tritium (T) isotope are made. This includes the quantification of intra- and inter-edge localised mode (ELM) contributions to the total W source in H-mode plasmas which vary owing to the complex flux compositions and energy distributions in the corresponding phases. The sputtering threshold behaviour and the spectroscopic composition analysis provides an insight in the dominating species and plasma phases causing W erosion. (ii) The interplay between the net and gross W erosion source is discussed considering (prompt) re-deposition, thus, the immediate return of W ions back to the surface due to their large Larmor radius, and surface roughness, thus, the difference between smooth bulk-W and rough W-coating components used in the JET divertor. Both effects impact on the balance equation of local W erosion and deposition. (iii) Post-mortem analysis reveals the net erosion/deposition pattern and the W migration paths over long periods of plasma operation identifying the net W transport to remote areas. This W transport is related to the divertor plasma regime, e.g. attached operation with high impact energies of impinging particles or detached operation, as well as to the applied magnetic configuration in the divertor, e.g. close divertor with good geometrical screening of W or open divertor configuration with poor screening.JET equipped with the ITER-like wall (ILW) provided unique access to the net W erosion rate within a series of 151 subsequent H-mode discharges (magnetic field: B-t = 2.0 T, plasma current: I-p = 2.0 MA, auxiliary power P-aux = 12 MW) in one magnetic configuration accumulating 900 s of plasma with particle fluences in the range of 5-6 x 10(26) D+ m(-2) in the semi-detached inner and attached outer divertor leg. The comparison of W spectroscopy in the intra-ELM and inter-ELM phases with post-mortem analysis of W marker tiles provides a set of gross and net W erosion values at the outer target plate. ERO code simulations are applied to both divertor leg conditions and reproduce the erosion/deposition pattern as well as confirm the high experimentally observed prompt W re-deposition factors of more than 95% in the intra- and inter-ELM phase of the unseeded deuterium H-mode plasma. Conclusions to the expected divertor conditions in ITER as well as to the JET operation in the DT plasma mixture are drawn on basis of this unique benchmark experiment

The effect of beryllium oxide on retention in JET ITER-like wall tiles

Preliminary results investigating the microstructure, bonding and effect of beryllium oxide formation on retention in the JET ITER-like wall beryllium tiles, are presented. The tiles have been investigated by several techniques: Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-ray (EDX), Transmission Electron microscopy (TEM) equipped with EDX and Electron Energy Loss Spectroscopy (EELS), Raman Spectroscopy and Thermal Desorption Spectroscopy (TDS). This paper focuses on results from melted materials of the dump plate tiles in JET. From our results and the literature, it is concluded, beryllium can form micron deep oxide islands contrary to the nanometric oxides predicted under vacuum conditions. The deepest oxides analyzed were up to 2-micron thicknesses. The beryllium Deuteroxide (BeOxDy) bond was found with Raman Spectroscopy. Application of EELS confirmed the oxide presence and stoichiometry. Literature suggests these oxides form at temperatures greater than 700 degrees C where self-diffusion of beryllium ions through the surface oxide layer can occur. Further oxidation is made possible between oxygen plasma impurities and the beryllium ions now present at the wall surface. Under Ultra High Vacuum (UHV) nanometric Beryllium oxide layers are formed and passivate at room temperature. After continual cyclic heating (to the point of melt formation) in the presence of oxygen impurities from the plasma, oxide growth to the levels seen experimentally (approximately two microns) is proposed. This retention mechanism is not considered to contribute dramatically to overall retention in JET, due to low levels of melt formation. However, this mechanism, thought the result of operation environment and melt formation, could be of wider concern to ITER, dependent on wall temperatures

Determination of isotope ratio in the divertor of JET-ILW by high-resolution H alpha spectroscopy: H-D experiment and implications for D-T experiment

The data of the H alpha high-resolution spectroscopy, collected on the multiple lines of sight, which cover the entire divertor space in poloidal cross-section, during the recent hydrogen-deuterium experiments in JET-ILW (ITER-like wall), are processed. A strong spatial inhomogeneity of the hydrogen concentration, H/(H + D), in divertor is found in many pulses. Namely, the H/(H + D) ratio may be lower in the inner divertor than that in the outer divertor by the values of 0.15-0.35, depending on the conditions of gas puffing and plasma heating. This effect suggests the necessity of spatially-resolved measurements of isotope ratio in the divertor in the upcoming deuterium-tritium experiments. Also, separation of the overlapped T alpha and D alpha spectral lines is shown to be a challenging task especially when the local Doppler-broadened (Gaussian) line shapes are noticeably distorted by the net inward flux of fast non-Maxwellian neutral atoms. We use the respective, formerly developed model of an asymmetric spectral line shape, while analysing the data of the first deuterium-tritium experiment in JET-C (carbon wall), and test the model via comparing the isotope ratio results with another diagnostic's measurements. This model is shown to increase the accuracy of tritium concentration measurements in the divertor

EDGE2D-EIRENE simulations of the influence of isotope effects and anomalous transport coefficients on near scrape-off layer radial electric field

EDGE2D-EIRENE (the 'code') simulations show that radial electric field, Er, in the near scrape-off layer (SOL) of tokamaks can have large variations leading to a strong local E x B shear greatly exceeding that in the core region. This was pointed out in simulations of JET plasmas with varying divertor geometry, where the magnetic configuration with larger predicted near SOL E-r was found to have lower H-mode power threshold, suggesting that turbulence suppression in the SOL by local E. x. B shear can be a player in the L-H transition physics (Delabie et al 2015 42nd EPS Conf. on Plasma Physics (Lisbon, Portugal, 22-26 June 2015) paper O3.113 (http://ocs.ciemat.es/EPS2015PAP/pdf/O3.113.pdf), Chankin et al 2017 Nucl. Mater. Energy 12 273). Further code modeling of JET plasmas by changing hydrogen isotopes (H-D-T) showed that the magnitude of the near SOL E-r is lower in H cases in which the H-mode threshold power is higher (Chankin et al 2017 Plasma Phys. Control. Fusion 59 045012). From the experiment it is also known that hydrogen plasmas have poorer particle and energy confinement than deuterium plasmas, consistent with the code simulation results showing larger particle diffusion coefficients at the plasma edge, including SOL, in hydrogen plasmas (Maggi et al 2018 Plasma Phys. Control. Fusion 60 014045). All these experimental observations and code results support the hypothesis that the near SOL E x B shear can have an impact on the plasma confinement. The present work analyzes neutral ionization patterns of JET plasmas with different hydrogen isotopes in L-mode cases with fixed input power and gas puffing rate, and its impact on target electron temperature, T-e, and SOL E-r. The possibility of a self-feeding mechanism for the increase in the SOL E-r via the interplay between poloidal E x B drift and target T-e is discussed. It is also shown that reducing anomalous turbulent transport coefficients, particle diffusion and electron and ion heat conductivities, leads to higher peak target T-e and larger E-r, suggesting the possibility of a positive feedback loop, under an implicitly made assumption that the E x B shear in the SOL is capable of suppressing turbulence

A power-balance model of the density limit in fusion plasmas: application to the L-mode tokamak

A power-balance model, with radiation losses from impurities and neutrals, gives a unified description of the density limit (DL) of the stellarator, the L-mode tokamak, and the reversed field pinch (RFP). The model predicts a Sudo-like scaling for the stellarator, a Greenwald- like scaling, alpha I-p(8/9), for the RFP and the ohmic tokamak, a mixed scaling, alpha (PIp4/9)-I-4/9, for the additionally heated L-mode tokamak. In a previous paper (Zanca et al 2017 Nucl. Fusion 57 056010) the model was compared with ohmic tokamak, RFP and stellarator experiments. Here, we address the issue of the DL dependence on heating power in the L-mode tokamak. Experimental data from high-density disrupted L-mode discharges performed at JET, as well as in other machines, arc taken as a term of comparison. The model fits the observed maximum densities better than the pure Greenwald limit

Long-lived coupled peeling ballooning modes preceding ELMs on JET

In some JET discharges, type-I edge localised modes (ELMs) are preceded by a class of low-frequency oscillations (Perez et al 2004 Nucl. Fusion 44 609). While in many cases the ELM is triggered during the growth phase of this oscillation, it is also observed that this type of oscillation can saturate and last for several tens of ms until an ELM occurs. In order to identify the nature of these modes, a wide pre-ELM oscillation database, including detailed pedestal profile information, has been assembled and analysed in terms of MHD stability parameters. The existence domain of these pre-ELM oscillations and the statistical distribution of toroidal mode numbers (n) up to n = 16 have been mapped in ballooning alpha (alpha(ball)) and either edge current density (J(edge)) or pedestal collisionality (nu(ee,ped)*) coordinates and compared to linear MHD stability predictions. The pre-ELM oscillations are reliably observed when the J/alpha ratio is high enough for the pedestal to access the coupled peeling-ballooning (PB) domain (aka stability nose). Conversely, when the pedestal is found to be in or near the high-n ballooning domain (which is at low J/alpha ratio), ELMs are usually triggered promptly, i.e. with no detectable pre-ELM oscillations, or with pre-ELM oscillations only observable on ECE whose n appears to be too high to be resolved by the magnetics. Individual discharges can sometimes exhibit a fairly wide range of pre-ELM mode numbers, but for a wider database, the statistical n-number domains are found to be well ordered along the J - alpha stability boundary and behave as expected from PB theory: the higher the J/alpha ratio, the lower the mode's measured n tends to be. Within the measurement uncertainties, the measured n is usually found to be compatible with the most unstable n predicted by the linear stability code MISHKA1. These results confirm the earlier hypothesis that these modes are coupled peeling-ballooning modes, and extend and generalise to higher-mode numbers the work by Huysmans et al (1998 Nucl. Fusion 38 179), who identified the lowest n modes as pure external kink modes. Since the destabilisation of PB modes is widely accepted to give rise to ELMs, the mode saturation and delayed ELM triggering that is sometimes observed is rather unexpected. Possibilities to reconcile the extended lifetime of these modes with current ELM models are briefly discussed, but will require further investigation