Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)α agonist fenofibrate and the PPARγ agonist pioglitazone

<p>Abstract</p> <p>Background</p> <p>All the peroxisome proliferator activated receptors (PPARs) are found to be expressed in bone cells. The PPARγ agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs) have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARα agonist fenofibrate (FENO) and the PPARγ agonist pioglitazone (PIO) on bone in intact female rats.</p> <p>Methods</p> <p>Rats were given methylcellulose (vehicle), fenofibrate or pioglitazone (35 mg/kg body weight/day) by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied.</p> <p>Results</p> <p>The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1.</p> <p>Conclusion</p> <p>We show opposite skeletal effects of PPARα and γ agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARα activation.</p

The Src inhibitor dasatinib accelerates the differentiation of human bone marrow-derived mesenchymal stromal cells into osteoblasts

The proto-oncogene Src is an important non-receptor protein tyrosine kinase involved in signaling pathways that control cell adhesion, growth, migration and differentiation. It negatively regulates osteoblast activity, and, as such, its inhibition is a potential means to prevent bone loss. Dasatinib is a new dual Src/Bcr-Abl tyrosine kinase inhibitor initially developed for the treatment of chronic myeloid leukemia. It has also shown promising results in preclinical studies in various solid tumors. However, its effects on the differentiation of human osteoblasts have never been examined.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Global optimization for human skin investigation in terahertz

In this paper, the electromagnetic interaction between human skin and terahertz radiation is investigated through the double Debye parameters' extraction algorithm. The changes of skin content are contrasted at the frequencies below one terahertz(THz) but the recent approaches could provide only a rough estimation. We propose an global optimization based identification, which results in globally accurate estimators in the frequency range up to two THz, and thus supports the validity of Debye model for Terahertz wave's propagation and reflection in skin. Simulation results confirm our prominent methodology. © 2012 IEEE

Debye parameter extraction for characterizing interaction of terahertz radiation with human skin tissue

This paper is concerned with parameter extraction for the double Debye model, which is used for analytically determining human skin permittivity. These parameters are thought to be the origin of contrast in terahertz (THz) images of skin cancer. The existing extraction methods could generate Debye models, which track their measurements accurately at frequencies higher than 1 THz but poorly at lower frequencies, where the majority of permittivity contrast between healthy and diseased skin tissues is actually observed. We propose a global optimization-based parameter extraction, which results in globally accurate tracking and thus supports the full validity of the Debye model for simulating human skin permittivity in the whole usable THz frequencies. Numerical results confirm viability of our novel methodology. © 1964-2012 IEEE

System identification for Terahertz wave's propagation and reflection in human skin

This paper is concerned with parameter identification for the double Debye model of the Terahertz wave's propagation and reflection in human skin. The existing methods could provide estimators, which are accurate at the frequencies higher than one THz but rather row at the lower frequencies, where the majority of contrast for differentiating the changes of skin content is present. We propose another approach by using parametric quadratic optimization to locate the global optimal estimator. Simulation results confirm our reliable and prominent technique. © 2012 IEEE