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.     

Crosslinked acrylic pressure‐sensitive adhesives. II. Effect of humidity on the crosslinking reaction

The effect of humidity during storage on the crosslinking reactions of isocyanate groups was investigated with attenuated total reflectance Fourier transform infrared spectroscopy with pressure‐sensitive adhesives composed of poly[ethyl acrylate‐co‐(2‐ethylhexyl acrylate)‐co‐(2‐hydroxyethyl methacrylate)] as a base resin and polyisocyanate as a crosslinker. A peak‐resolving analysis of the amide II region revealed four bands. According to an analysis of the Fourier transform infrared spectra of the model compounds, these four bands were assigned to free urethane linkages, hydrogen‐bonded urethane linkages, free urea linkages, and hydrogen‐bonded urea linkages. As expected, storage under humid conditions led to the formation of free and hydrogen‐bonded urea linkages corresponding to the promotion of isocyanate consumption. Peak resolution of the amide II region was found to be a reasonable way of monitoring urethane and urea linkages during crosslinking reactions. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3039–3045, 2003     

Reduction mechanism of tioglycolic acid on keratin fibers using microspectrophotometry and FT-Raman spectroscopy

In order to investigate the reduction mechanism of thioglycolic acid (TG) on the keratin fibers, cross-sectional samples of white human hair treated with TG were prepared. The heterogeneous reaction between TG and keratin fibers involving the diffusion of TG into human hair was analyzed at the molecular level using microspectrophotometry and FT-Raman spectroscopy. The diffusion of TG into human hair clearly increased by increasing the treatment time and by raising pH. The TG relative concentration and the disconnected relative concentration of disulfide (–SS–) groups at various depths of the hair samples with pH 9.0 were in good agreement, indicating that the reaction rate (the disconnection of –SS– groups) was faster than the diffusion rate of TG into human hair. From these experiments, we demonstrated that TG diffuses gradually beyond the cuticle region, and toward the inside of the cortex region along with the disconnection of –SS– groups.     

Effects of Neodymium Concentration on Optical Characteristics of Polycrystalline Nd:YAG Laser Materials

A neodymium-doped yttrium-aluminum garnet (Y₃A1₅O₁₂, YAG) (Nd:YAG) ceramic that contained 0.3–4.8 at.% neodymium additives and exhibited nearly the same optical properties as those of a single crystal was fabricated by a solid-state reaction method using high-purity powders. Although the integrated absorption intensity of the ²H_9/2+⁴F_5/2 bands simply increased as the neodymium concentration in the YAG ceramics decreased, the fluorescence intensity of the 2.4 at.% Nd:YAG ceramic was the strongest among Nd:YAG ceramics with various neodymium concentrations and a 0.9 at.% Nd:YAG single crystal. An oscillation experiment was performed on a continuous-wave (cw) laser with a diode-laser exciting system using those ceramics and the single crystal. The oscillation threshold and slope efficiency in that analysis were 309 mW and 28%, respectively, for the 1.1 at.% Nd:YAG ceramics and 356 mW and 40%, respectively, for the 2.4 at.% Nd:YAG ceramics. The lasing characteristics of the ceramics in the present work were superior to those of a 0.9 at.% Nd:YAG single crystal that was fabricated by the Czochralski (Cz) method.     

Difference between human and guinea pig Hageman factors in activation by bacterial proteinases: cleavage site shift due to local amino acid substitutions may determine the activation efficiency of serine proteinase zymogens

Human and guinea pig Hageman factors have been subjected to the action of pseudomonal elastase and serratial E15 proteinase. The pseudomonal elastase cleaved 22-24% of the human molecule at Arg353-Val354, and the remainder at Gly357-Leu358 resulting in the generation of about 20% of potential activity as activated Hageman factor, compared with trypsin activation, while it hydrolyzed Arg340-Ile341 bond in guinea pig molecule and generated about 75% of activity as activated Hageman factor. The serratial proteinase did not hydrolyze the essential cleavage site (Arg353-Val354) of the human zymogen but Gly356-Gly357 (30%) and Gly357-Leu358 (70%) bonds. Both products showed no activity. The guinea pig zymogen, in contrast, was cleaved mostly at Arg340-Ile341 (70%) and less abundantly at Gly344-Leu345 (30%), generating about 85% of the whole potential activity as activated Hageman factor. From the high correspondence between the proportions of activation and of hydrolysis at the essential cleavage site in activation, it was concluded that hydrolysis of the bonds different from the essential bond did not cause activation, even when the spatial separation was only 3 or 4 residues. Considering the amino acid differences between human and guinea pig Hageman factors, -Met351-Thr-Arg-Val-Val-Gly-Gly-Leu-Val-Ala360- and -Leu338-Ser-Arg-Ile-Val-Gly-Gly-Leu-Val-Ala347-, respectively, it was realized that even the minor amino acid substitutions caused the cleavage site shift which resulted in significant differences in activation efficiency of the proteinase zymogens.     

Thermal stability of reinforced Nb3Sn composite superconductor under cryocooled conditions

Several types of reinforced Nb₃Sn wires have been developed to prevent reduction of superconducting properties by applying a strong electromagnetic force. To fabricate a cryocooled magnet using those reinforced wires, we experimentally measured the minimum quench energy (MQE) under cryocooled conditions of some reinforced Nb₃Sn wires. As a result, it became clear that thermal stability expressed as MQE was controlled by the temperature margin between the temperature of the operating condition and the transition temperature from superconductivity to normal. Using the FEM analysis, it was realized that the cause of the decline in thermal stability for the reinforced wires was the low thermal conductivity of the reinforced materials.     

Voltage-time characteristics for steep-front impulse voltages ofparticle-contaminated spacers in SF6 gas-insulated switchgear

The voltage-time characteristics of spacer surfaces for steep-front impulse waves are investigated under a particle-contaminated condition in SF₆ gas. The characteristics are measured as a function of particle length, particle position, and space shapes. Flashover voltages monotonically increase in the submicrosecond region as time to flashover is shorter, and are a minimum in the 1 μs region. Applicability of the equal voltage-time area criterion for estimating the voltage-time characteristics is discussed and the estimation is clarified. Moreover, it is demonstrated that an optimized spacer with ribs greatly improves flashover voltages in the submicrosecond region as well as in the 1 μs and power frequency region     

Formation and Characterization of Ce3ZrO8 Prepared by the Hydrazine Method

A compound denoted as (Ce_0.75Zr_0.25)O₂ (Ce, ZrO₈) is formed near room temperature from cerium and zirconium nitrates using hydrazine monohydrate. It has a cubic unit cell with a = 0.5342 nm. Characterization of powders heated to various temperatures at 10°C/min demonstrates that the specific surface area does not decrease below 20 mVg until >1000°C.     

Hinokitiol induces differentiation of teratocarcinoma F9 cells

Hinokitiol, a constituent of the wood of Chamaecyparis taiwanensis, was found to induce differentiation of teratocarcinoma F9 cells. When examined by the agar-overlay method, in which expression of plasminogen activator as a differentiation marker protein was detected, this compound exhibited a dose- and time-dependent induction. Induction of differentiation by hinokitiol occurred irreversibly and required its addition for more than 12h. Among its structure-related compounds tested, tropolone and two colchicine-related compounds exerted potent activities comparable to that of hinokitiol. These findings indicate that free tropolone structure in the molecules plays an essential role in inducing differentiation of F9 cells. Hinokitiol showed a strong inhibitory effect of DNA synthesis in very early stages of culture, suggesting that this effect may be responsible for triggering differentiation of F9 cells.     

Three-dimensional pin power reconstruction for the axially heterogeneous region in BWR

A three-dimensional pin power reconstruction method was proposed and verified by applying to the axially heterogeneous region problem of the BWR core calculation. Because the production assembly calculation has been carried out by two-dimensional deterministic calculation methods like current coupling collision probability or the method of characteristics, it has been difficult to predict the detailed three-dimensional heterogeneous pin power distribution of the axially heterogeneous region. Consequently, only radial intranodal homogeneous power distributions have been considered, and axial intranodal homogeneous power distributions have not been considered in the estimation of linear-heat-generation-ratio at common BWR core calculations.