Biochemical and clinical relevance of alpha lipoic acid: antioxidant and anti-inflammatory activity, molecular pathways and therapeutic potential

The molecular nature of lipoic acid (LA) clarifies its capability of taking part to a variety of biochemical reactions where redox state is meaningful. The pivotal action of LA is the antioxidant activity due to its ability to scavenge and inactivate free radicals. Furthermore, LA has been shown to chelate toxic metals both directly and indirectly by its capability to enhance intracellular glutathione (GSH) levels. This last property is due to its ability to interact with GSH and recycle endogenous GSH. LA exhibits significant antioxidant activity protecting against oxidative damage in several diseases, including neurodegenerative disorders. Interestingly, LA is unique among natural antioxidants for its capability to satisfy a lot of requirements, making it a potentially highly effective therapeutic agent for many conditions related with oxidative damage. In particular, there are evidences showing that LA has therapeutic activity in lowering glucose levels in diabetic conditions. Similarly, LA supplementation has multiple beneficial effects on the regression of the mitochondrial function and on oxidative stress associated with several diseases and aging

Thermal effects on nonlinear acceleration waves in the Biot theory of porous media

We generalize a theory of Biot for a porous solid based on nonlinear elasticity theory to incorporate temperature effects. Acceleration waves are studied in detail in the fully nonlinear theory. The wavespeeds are found explicitly and the amplitudes are then determined. The possibility of shock formation is discussed

Uniqueness of Solutions in Thermopiezoelectricity of Nonsimple Materials

This article presents the theory of thermopiezoelectricity in which the second displacement gradient and the second electric potential gradient are included in the set of independent constitutive variables. This is achieved by using the entropy production inequality proposed by Green and Laws. At first, appropriate thermodynamic restrictions and constitutive equations are obtained, using the well-established Coleman and Noll procedure. Then, the balance equations and the constitutive equations of linear theory are derived, and the mixed initial-boundary value problem is set. For this problem a uniqueness result is established. Next, the basic equations for the isotropic case are derived. Finally, a set of inequalities is obtained for the constant constitutive coefficients of the isotropic case that, on the basis on the previous theorem, ensure the uniqueness of the solution of the mixed initial-boundary value problem

Discontinuity waves in temperature and diffusion models

We analyse shock wave behaviour in a hyperbolic diffusion system with a general forcing term which is qualitatively not dissimilar to a logistic growth term. The amplitude behaviour is interesting and depends critically on a parameter in the forcing term. We also develop a fully nonlinear acceleration wave analysis for a hyperbolic theory of diffusion coupled to temperature evolution. We consider a rigid body and we show that for three-dimensional waves there is a fast wave and a slow wave. The amplitude equation is derived exactly for a one-dimensional (plane) wave and the amplitude is found for a wave moving into a region of constant temperature and solute concentration. This analysis is generalized to allow for forcing terms of Selkov–Schnakenberg, or Al Ghoul-Eu cubic reaction type. We briefly consider a nonlinear acceleration wave in a heat conduction theory with two solutes present, resulting in a model with equations for temperature and each of two solute concentrations. Here it is shown that three waves may propagate

SPARC expression in CML is associated to imatinib treatment and to inhibition of leukemia cell proliferation

BACKGROUND: SPARC is a matricellular glycoprotein with growth-inhibitory and antiangiogenic activity in some cell types. The study of this protein in hematopoietic malignancies led to conflicting reports about its role as a tumor suppressor or promoter, depending on its different functions in the tumor microenvironment. In this study we investigated the variations in SPARC production by peripheral blood cells from chronic myeloid leukemia (CML) patients at diagnosis and after treatment and we identified the subpopulation of cells that are the prevalent source of SPARC. METHODS: We evaluated SPARC expression using real-time PCR and western blotting. SPARC serum levels were detected by ELISA assay. Finally we analyzed the interaction between exogenous SPARC and imatinib (IM), in vitro, using ATP-lite and cell cycle analysis. RESULTS: Our study shows that the CML cells of patients at diagnosis have a low mRNA and protein expression of SPARC. Low serum levels of this protein are also recorded in CML patients at diagnosis. However, after IM treatment we observed an increase of SPARC mRNA, protein, and serum level in the peripheral blood of these patients that had already started at 3 months and was maintained for at least the 18 months of observation. This SPARC increase was predominantly due to monocyte production. In addition, exogenous SPARC protein reduced the growth of K562 cell line and synergized in vitro with IM by inhibiting cell cycle progression from G1 to S phase. CONCLUSION: Our results suggest that low endogenous SPARC expression is a constant feature of BCR/ABL positive cells and that IM treatment induces SPARC overproduction by normal cells. This exogenous SPARC may inhibit CML cell proliferation and may synergize with IM activity against CML

On microstretch thermoviscoelastic composite materials

In this paper we derive a continuum theory for a thermoviscoelastic composite using an entropy production inequality proposed by Green and Laws, presented in Lagrangian description. The composite is modeled as a mixture of a microstretch viscoelastic material of KelvineVoigt type and a microstretch elastic solid. The strain measures and the basic laws are shown and the thermodynamic restrictions are established. Then the linear theory is considered and the constitutive equations are given in both anisotropic and isotropic cases. Finally, a uniqueness result is established within the framework of the linear theory

Nonlinear acceleration wave propagation in the DKM theory

We study the evolutionary development of an acceleration wave propagating in a saturated porous material according to a Biot theory proposed by Donskoy, Khashanah and McKee. The theory is fully nonlinear, includes dissipation, and the analysis presented is exact. We derive sufficient conditions to show that two distinct waves propagate, a fast wave and a slower wave. A solution for the wave amplitude is presented for a wave moving into an equilibrium region