The Effect of Melatonin on Behavioral, Molecular, and Histopathological Changes in Cuprizone Model of Demyelination

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. The protective effects of melatonin (MLT) on various neurodegenerative diseases, including MS, have been suggested. In the present study, we examined the effect of MLT on demyelination, apoptosis, inflammation, and behavioral dysfunctions in the cuprizone toxic model of demyelination. C57BL/6J mice were fed a chaw containing 0.2 % cuprizone for 5 weeks and received two doses of MLT (50 and 100 mg/kg) intraperitoneally for the last 7 days of cuprizone diet. Administration of MLT improved motor behavior deficits induced by cuprizone diet. MLT dose-dependently decreased the mean number of apoptotic cells via decreasing caspase-3 and Bax as well as increasing Bcl-2 levels. In addition, MLT significantly enhanced nuclear factor-κB activation and decreased heme oxygenase-1 level. However, MLT had no effect on interleukin-6 and myelin protein production. Our data revealed that MLT improved neurological deficits and enhanced cell survival but was not able to initiate myelin production in the cuprizone model of demyelination. These findings may be important for the design of potential MLT therapy in demyelinating disorders, such as MS. © 2015, Springer Science+Business Media New York

CFD-DEM Analysis of Particle Attrition in a Jet in a Fluidised Bed

In fluidised bed processes, the solids are in vigorous motion and thus inevitably subjected to mechanical stresses due to inter-particle and particle-wall impacts. These stresses lead to a gradual degradation of the particles by surface wear, abrasion and body fragmentation commonly termed attrition. One significant contribution of attrition comes from the air jets of the fluidised bed distributor. Particles are entrained into the air jet, where they get accelerated and impacted onto the fluidised bed particles. The jet induced attrition only affects the part of the bed which is limited by the jet length, where the mode of attrition is largely collisional. The overall jet attrition rate is therefore the result of the combination of the single particle damage and the flux of particles entering into that region. The attrition behaviour of particles in the jet region is analysed by evaluating their propensity of breakage experimentally and by simulating an air-jet in a bed of particles by CFD-DEM. The frequency of collisions and impact velocities are estimated from which the attrition due to a single air-jet is predicted

Modeling and Simulation of Interfacial Turbulent Flows

Majority of the fluid flows in nature and industries are turbulent flows. Due to their complexity, modeling and simulation of turbulent flows are still among the top research topics in the field of fluid mechanics. The objective of this work is to consider the turbulence effects at the interface. The presence of interface affects the turbulence structures and they become anisotropic near the interface. In this work, the main objective is to consider the fluctuations of the interface topology and their effects on the volume fraction and the surface tension force at the interface. These effects are important under some circumstances especially when the shape of the interface changes rapidly and abruptly. The surface tension forces and the volume fraction-velocity fluctuation correlation have also important impact on the interface topology and its complicated features such as coalescence and breakup. Different new models are presented and the impacts of those parameters on the flow at the interface are presented in this work. In developing the models for mean velocity-volume fraction fluctuations the inhomogeneity of the flow at the interface is taken into account. Both Reynolds Averaged Navier-Stokes Equations and the Large Eddy Simulation Techniques were used to simulate turbulent interfacial flows and implement the novel models introduced in this work. The Kelvin-Helmholtz instability, two-dimensional and three dimensional jets, and water/oil phase separation were simulated numerically and the results were compared with corresponding valid data and the accuracy of the models was examined

Modulation of aflatoxin B1 cytotoxicity and aflatoxin M1 synthesis by natural antioxidants in a bovine mammary epithelial cell line

Aflatoxin (AF) B1, a widespread food and feed contaminant, is bioactivated by drug metabolizing enzymes (DME) to cytotoxic and carcinogenic metabolites like AFB1-epoxide and AFM1, a dairy milk contaminant. A number of natural antioxidants have been reported to afford a certain degree of protection against AFB1 (cyto)toxicity. As the mammary gland potentially participates in the generation of AFB1 metabolites, we evaluated the role of selected natural antioxidants (i.e. curcumin, quercetin and resveratrol) in the modulation of AFB1 toxicity and metabolism using a bovine mammary epithelial cell line (BME-UV1). Quercetin and, to a lesser extent, resveratrol and curcumin from Curcuma longa (all at 5 \u3bcM) significantly counteracted the AFB1-mediated impairment of cell viability (concentration range: 96\u2013750 nM). Moreover, quercetin was able to significantly reduce the synthesis of AFM1. The quantitative PCR analysis on genes encoding for DME (phase I and II) and antioxidant enzymes showed that AFB1 caused an overall downregulation of the detoxifying systems, and mainly of GSTA1, which mediates the GSH conjugation of the AFB1-epoxide. The negative modulation of GSTA1 was efficiently reversed in the presence of quercetin, which significantly increased GSH levels as well. It is suggested that quercetin exerts its beneficial effects by depressing the bio-transformation of AFB1 and counterbalancing its pro-oxidant effects

Effect of Structure on Strength of Agglomerates using Distinct Element Method

Knowledge of agglomerate strength is highly desirable for compression and tableting, dissolution and dispersion and mitigation of dust formation. The behaviour of agglomerates is affected by parameters such as density, agglomerate size, primary particle size, and interparticle bond strength. The method of agglomeration influences the evolution of structure, and this in turn affects its strength. Furthermore, the methods of strength characterisation, i.e. quasi-static or impact produce different results. To understand the role of structure and the influence of test method, agglomerate failure behaviour has been analysed by the use of the Distinct Element Method (DEM). We report on our work on the simulation of the breakage of the agglomerates for different porosities and impact conditions, where the role of impact speed and angle and type of contact bonding model have been evaluated. The adhesive contact model of JKR is used to form an agglomerate. The effect of the bonding level on the strength and size distribution of the clusters released as a result of failure has been investigated. This work also evaluates the effect of structure (porosity) on the strength of the agglomerates

Fluid-particle energy transfer in spiral jet milling

Spiral jet milling is a size reduction process driven by the fluid energy of high velocity gas jets. Inter-particle and particle-wall interactions are responsible for size reduction. The process is energy intensive, but inefficient. The underlying mechanisms for size reduction in the mill are also not very well understood. The optimum grinding conditions are still currently found by trial and error experimentation. In this work, the Discrete Element Method coupled with Computational Fluid Dynamics is used to investigate the effects of different parameters on the particle collisional behaviour in a spiral jet mill. These include the particle concentration in the grinding chamber, the particle size, and the fluid power input. We report on our work analysing the efficiency of energy transfer and how it can be improved by changing the milling conditions and particle properties