247 research outputs found
On the Finite Energy Weak Solutions to a System in Quantum Fluid Dynamics
In this paper we consider the global existence of weak solutions to a class
of Quantum Hydrodynamics (QHD) systems with initial data, arbitrarily large in
the energy norm. These type of models, initially proposed by Madelung, have
been extensively used in Physics to investigate Supefluidity and
Superconductivity phenomena and more recently in the modeling of semiconductor
devices . Our approach is based on various tools, namely the wave functions
polar decomposition, the construction of approximate solution via a fractional
steps method, which iterates a Schr\"odinger Madelung picture with a suitable
wave function updating mechanism. Therefore several \emph{a priori} bounds of
energy, dispersive and local smoothing type allow us to prove the compactness
of the approximating sequences. No uniqueness result is provided
On the vanishing electron-mass limit in plasma hydrodynamics in unbounded media
We consider the zero-electron-mass limit for the Navier-Stokes-Poisson system
in unbounded spatial domains. Assuming smallness of the viscosity coefficient
and ill-prepared initial data, we show that the asymptotic limit is represented
by the incompressible Navier-Stokes system, with a Brinkman damping, in the
case when viscosity is proportional to the electron-mass, and by the
incompressible Euler system provided the viscosity is dominated by the electron
mass. The proof is based on the RAGE theorem and dispersive estimates for
acoustic waves, and on the concept of suitable weak solutions for the
compressible Navier-Stokes system
Effect of the oral application of a highly selective MMP-13 inhibitor in three different animal models of rheumatoid arthritis
OBJECTIVE: In the present study we evaluated the decrease of cartilage destruction by a novel orally active and specific MMP-13 inhibitor in three different animal models of rheumatoid arthritis (RA). MATERIALS AND METHODS: The SCID mouse co-implantation model of RA, collagen-induced arthritis (CIA) model in mice and the antigen induced arthritis model (AIA) in rabbits were used. RESULTS: In the SCID mouse co-implantation model this inhibitor resulted in reduced cartilage destruction by 75%. In the CIA model of RA, the MMP-13 inhibitor resulted in a significant and dose dependent decrease in clinical symptoms as well as of cartilage erosion by 38% (30 mg/kg), 28% (10 mg/kg) and 21% (3 mg/kg). No significant effects were observed in the AIA model. No toxic effects were observed in all three animal models. CONCLUSION: Although several MMPs in concert with other proteinases play a role in the process of cartilage destruction, there is a need for highly selective MMP inhibitors to reduce severe side effects that occur with non-specific inhibitors. Significant inhibition of MMP-13 reduced cartilage erosions in two out of three tested animal models of RA. These results strongly support the development of this class of drugs to reduce or halt joint destruction in patients with RA
Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis
OBJECTIVE: We have recently shown a significant reduction in cytokine-induced transcription of type I collagen and fibronectin in systemic sclerosis (SSc) skin fibroblasts upon treatment with trichostatin A (TSA). Moreover, in a mouse model of fibrosis, TSA prevented the dermal accumulation of extracellular matrix. The purpose of this study was to analyze the silencing of histone deacetylase 7 (HDAC-7) as a possible mechanism by which TSA exerts its antifibrotic function. METHODS: Skin fibroblasts from patients with SSc were treated with TSA and/or transforming growth factor beta. Expression of HDACs 1-11, extracellular matrix proteins, connective tissue growth factor (CTGF), and intercellular adhesion molecule 1 (ICAM-1) was analyzed by real-time polymerase chain reaction, Western blotting, and the Sircol collagen assay. HDAC-7 was silenced using small interfering RNA. RESULTS: SSc fibroblasts did not show a specific pattern of expression of HDACs. TSA significantly inhibited the expression of HDAC-7, whereas HDAC-3 was up-regulated. Silencing of HDAC-7 decreased the constitutive and cytokine-induced production of type I and type III collagen, but not fibronectin, as TSA had done. Most interestingly, TSA induced the expression of CTGF and ICAM-1, while silencing of HDAC-7 had no effect on their expression. CONCLUSION: Silencing of HDAC-7 appears to be not only as effective as TSA, but also a more specific target for the treatment of SSc, because it does not up-regulate the expression of profibrotic molecules such as ICAM-1 and CTGF. This observation may lead to the development of more specific and less toxic targeted therapies for SSc
PU.1 controls fibroblast polarization and tissue fibrosis
Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs
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