Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

Characterization of a cartilage-derived 66-kDa protein (RGD-CAP/beta ig-h3) that binds to collagen

Malignant human gliomas are the most common forms of primary tumors in the central nerve system. Due to their location and invasive nature, treatment so far has been mainly palliative. Thus, understanding the molecular detail of tumor transformation and progression is crucial for developing effective therapeutic strategy for this fetal tumor. Among the genetic alternations found in these tumors, p53 inactivation and PDGF/PDGFR activation represent the early events, and the loss of chromosome 10 and gene amplification and rearrangement of EGFR represent the late events. Studies with both glioma cell lines and primary tumor tissues have strongly suggested that TGF-alpha and EGFR function as an important autocrine loop in supporting proliferation of human glioma, especially in high grade glioma, since elevated TGF-alpha expression is also found in these high grade tumors. Furthermore, down regulation of the expression of TGF-alpha by antisense constructs has been shown to inhibit several types of human tumor cell growth including glioma. Other means of therapeutic approaches using this autocrine loop as a target also include the use of monoclonal antibodies and their cytotoxic conjugated. Considerable understanding of the EGFR-mediated signal transduction pathways has become available recently, which including GRB2/mSOS1 mediated MAP kinase activation; JAK/STATs pathway; PLC-gamma pathway. However, much work still needs to be done before a specific component of these pathways can be applied for effective control of tumor growth in the clinic.     

Oxygenation in the rabbit myocardium: assessment with susceptibility-dependent MR imaging

PURPOSE: To determine the feasibility of using hemoglobin (Hb) desaturation as an indicator of myocardial oxygenation. MATERIALS AND METHODS: High-resolution gradient-echo nuclear magnetic resonance (MR) images of isolated, blood-perfused rabbit hearts were obtained at various blood oxygenation levels. The hearts were perfused at 37 degrees C with a Langendorff apparatus modified for nuclear MR imaging. The perfusate contained bovine red blood cells in a cardioplegic solution that eliminated motion artifacts and minimized arteriovenous oxygenation differences. Hb saturation was varied (7%-100%) randomly. Perfusion pressure was continuously monitored, and blood samples were obtained. RESULTS: There was a substantial correlation between image signal intensity in the myocardium and Hb saturation in the blood, believed to be due to susceptibility effects of the paramagnetic species deoxyhemoglobin. CONCLUSION: Direct and noninvasive determination of regional Hb saturation with susceptibility-dependent MR imaging may provide information regarding regional myocardial O2 content.     

Development of 170 GHz/500 kW gyrotron

A development of 170GHz/500kW level gyrotron was carried out as R&D work of ITER. The oscillation mode is TE_31,8. In a short pulse experiment, the maximum power of 750kW was achieved at 85kV/40A. The efficiency was 22%. In the depressed collector operation, 500kW/36%/50ms was obtained. The maximum efficiency of 40% was obtained at P_RF=470kW whereas the power decrease by the electron trapping was observed. Pulse extension was done up to 10s at P_RF=170kW with the depressed collector operation. The power was limited by the temperature increase of the output window.     

A load dispatch method using fractional programming and semidefinite programming

This paper describes a load dispatch method which minimizes power cost—[fuel cost]/[electric output]—for a power system with thermal plants and energy storage facilities. The proposed method employs fractional programming to convert a minimization problem with fractional objective function to a series of quadratic minimization problems, and semidefinite programming to solve converted problems. The method provides the optimum time‐dependent power output/input and storage level of energy storage facilities as well as time‐dependent power output of thermal plants. The method has been applied to a power system with five thermal plants, two energy storage facilities of various performances, and five load demands. The optimum load scheme of four time mesh points is obtained for the thermal plants and energy storage facilities. The fractional programming successfully converges the optimal scheme through a few iterations. The semidefinite programming deals with a variable matrix of 164 dimensions, and 185 inequality constraints. © 2001 Scripta Technica, Electr Eng Jpn, 138(2): 49–58, 2002     

Surface Hardening of Carbon Steel Using High Powered YAG Laser

A high powered YAG laser with kaleidoscope for surface modification was applied to the surface hardening of carbon steels containing 0. 18-0.54 wt% C without the absorbents, and the relationships between laser processing and surface hardening were investigated by hardness and microstructure. The structure of the hardened zone underwent complete martensitic transformation in all of the carbon steels tested, and its hardness increased with greater carbon content. Under identical irradiated conditions, the hardened zone expanded with increasing carbon content. A hardened zone extending from the surface to a depth of 1.0 mm was obtained at a laser power of 1.0 kW and a scanning speed of 1 mm/sec. It was found that in the surface hardening of carbon steels, a high powered YAG laser can be used to control the hardened zone by selecting the appropriate irradiation conditions, however, the hardened zone was affected by the assistant gas and the flow rate.     

Atomic force microscopic study on DNA-wrapping for different diameter single-wall carbon nanotubes

DNA-wrapped single-wall carbon nanotubes (DNA-SWNT hybrids) prepared from different diameter HiPco- and Arc-SWNTs were investigated by atomic force microscopy. The mean diameter of DNA-HiPco-SWNT hybrids is 1.94 nm that is consistent with one HiPco-SWNT (~ 0.9 nm) wrapped by DNA (~ 1 nm). On the other hand, the mean diameter of DNA-Arc-SWNT hybrids is 3.74 nm that can correspond to one Arc-SWNT (~ 1.4 nm) wrapped by several layers of DNA. It is suggested that the DNA-wrapping mechanism for large diameter Arc-SWNTs is different from that for small diameter HiPco-SWNTs.     

Mechanical property changes in sapphire by nickel ion implantation and their dependence on implantation temperature

Sapphire plates, cut parallel to an {0001} plane, have been implanted with 300 keV nickel ions to doses ranging from 5×10¹² to 1×10¹⁷ Ni cm^–2 at specimen temperatures of 100, 300 and 523 K, in order to investigate the effect of implantation temperature on the mechanical property changes in sapphire caused by ion implantation. The measured changes in surface hardness, surface fracture toughness and bulk flexural strength were found to depend strongly on the implantation temperature, and were largely correlated with the residual surface compressive stress measured by using a cantilever beam technique. The surface amorphization that occurred only by the implantation at 100 K and at doses larger than 2×10s15 Ni cm^–2 reduced the hardness to 0.6 relative to the value of the unimplanted sapphire, and considerably increased the surface plasticity. Furthermore, the amorphization was found to involve a large volume expansion of 30% and to change drastically the apparent shape and size of a Knoop indentation flaw made prior to implantation. This effect was suggested to reduce stress concentrations at surface flaws and hence to increase the flexural strength.