Effects of intermittent fasting on experimental autoimune encephalomyelitis in C57BL/6 mice

Several religions recommend periods of fasting. One of the most frequently asked questions of MS patients before the holy month of Ramadan is weather fasting might have an unfavorable effect on their disease course. This debate became more challenging after the publication of experimental studies suggesting that calorie restriction prior to disease induction attenuates disease severity. We conducted this study to assess early and late effects of fasting on the animal model of MS, known as autoimmune encephalomyelitis. EAE was induced in the C57BL/6 mice, using Myelin Oligodendrocyte Glycopeptide (MOG) 35-55 and they fasted every other day either after the appearance of the first clinical sign or 30 days after disease induction for ten days. Thereafter, the mice were sacrificed for further histological and immunological evaluations. Intermittent fasting after the establishment of EAE did not have any unfavorable effect on the course of disease. Moreover, fasting at the early phase of disease alleviated EAE severity by ameliorating spinal cord demyelination. Fasting suppressed the secretion of IFN-γ, TNF-α and raised IL-10 production in splenocytes. Fasting was also associated with a lower percent of cytotoxicity. Intermittent fasting not only had no unfavorable effect on EAE but also reduced EAE severity if started at early phase of disease. © Summer 2016, Iran J Allergy Asthma Immunol. All rights reserved

Effect of oral genistein administration in early and late phases of allergic encephalomyelitis

Objective(s): Experimental allergic encephalomyelitis (EAE) is an autoimmune disease validated as animal model of multiple sclerosis (MS). Administration of genistein, a phytoestrogenic component of soy, to mice at the onset of EAE is known to attenuate the clinical signs of the disease. The potential effects of genistein on established EAE is less studied. In the current study, we aimed to compare the effects of genistein administration on EAE severity in early and late phases of the disease. Materials and Methods: The C57BL/6 mice were induced with EAE, using MOG 35-55 and gavaged with genistein (300 mg/kg) either after the appearance of the first clinical sign or 30 days post disease induction for ten days. 24 hr after the last gavage, mice were sacrificed. Brains and spleens were removed for assessing lymphocyte proliferation, cell cytotoxicity, and cytokine profile. Spinal cords were dissected to assess the amount of demyelination using Luxol fast blue/cresyl violet staining. Results: Administering mice with genistein, after the establishment of EAE, did not reverse the clinical signs of disease. However, treating with genistein at the onset of disease alleviated the clinical signs by reducing neuronal demyelination. Genistein suppressed the production of IFN-γ and enhanced IL-10 secretion in splenocyte and brain. Genistein also reduced IL-12 and TNF-α secretion in splenocytes, suppressed the proliferation of T-cells, and reduced the cell cytotoxicity. Conclusion: Genistein oral therapy might only reduce EAE severity if started in early phases of the disease

A non-intrusive reduced-order model for compressible fluid and fractured solid coupling and its application to blasting

This work presents the first application of a non-intrusive reduced order method to model solid interacting with compressible fluid flows to simulate crack initiation and propagation. In the high fidelity model, the coupling process is achieved by introducing a source term into the momentum equation, which represents the effects of forces of the solid on the fluid. A combined single and smeared crack model with the Mohr–Coulomb failure criterion is used to simulate crack initiation and propagation. The non-intrusive reduced order method is then applied to compressible fluid and fractured solid coupled modelling where the computational cost involved in the full high fidelity simulation is high. The non-intrusive reduced order model (NIROM) developed here is constructed through proper orthogonal decomposition (POD) and a radial basis function (RBF) multi-dimensional interpolation method.The performance of the NIROM for solid interacting with compressible fluid flows, in the presence of fracture models, is illustrated by two complex test cases: an immersed wall in a fluid and a blasting test case. The numerical simulation results show that the NIROM is capable of capturing the details of compressible fluids and fractured solids while the CPU time is reduced by several orders of magnitude. In addition, the issue of whether or not to subtract the mean from the snapshots before applying POD is discussed in this paper. It is shown that solutions of the NIROM, without mean subtracted before constructing the POD basis, captured more details than the NIROM with mean subtracted from snapshots