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.     

A wafer level monitoring method for plasma-charging damage usingantenna PMOSFET test structure

A novel monitoring method for plasma-charging damage is proposed. This method performs a quick and accurate evaluation using antenna PMOSFET. It was found that not only hot-carrier (HC) lifetime but transistor parameters such as initial gate current and substrate current were changed according to the degree of plasma-charging damage. However, the present work suggests that monitoring the shift of drain current after a few seconds of HC stress is a more accurate method to indicate plasma-charging damage. The monitoring method using the present test structure is demonstrated to be useful for realizing highly reliable devices     

Studies on chitin. IX. Crosslinking of water-soluble chitin and evaluation of the products as adsorbents for cupric ion

Water-soluble chitin was successfully crosslinked to varying extents with glutaraldehyde in homogeneous aqueous solutions to improve the properties as an adsorbent for metal cations, and the effects of crosslinking were discussed. Complete insolubilization was achieved with the fivefold excess aldehyde, but, in terms of adsorptivity of Cu²⁺, the chitin crosslinked at an aldehyde/amino group ratio of 1.0 was found to exhibit remarkable capacity and was much superior to others. The desorption of Cu²⁺ from the adsorption complex was also attained effectively at pH 2.0. These results indicated that the loose crosslinking was quite simple and efficient to produce high capacity adsorbents for practical use. Thermal behavior of the crosslinked chitin was examined by TMA and TGA; a softening phenomenon was observed at 145°C.     

Theoretical model for flash generation

Reduction of flash generated in a gas vent is of great concern for manufacturers of electronic parts. The present study proposes a theoretical model for flash generation through consideration of flow characteristics in a gas vent. The model predicts the factors controlling flash, i.e., material parameters such as zero‐shear viscosity, crystallization temperature, thermal conductivity, and heat capacity, and process parameters such as injection and mold wall temperatures, packing pressure, and the clearance of a gas vent. On the other hand, we measure the amount of flash generated in the molding of poly(phenylene sulfide) (PPS) composites containing glass fiber and spherical fillers (CaCO₃ or Al₂O₃). Flash reduces with decreasing size of spherical fillers. These experimental data are successfully interpreted using the flash model. Polym. Eng. Sci., 45:198–206, 2005. © 2005 Society of Plastics Engineers     

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.     

Evaluation of myocardial damage using 123I-BMIPP imaging in patients with vasospastic angina

The purpose of this study is to determine whether left ventricular dysfunction following coronary artery spasm by 123I-BMIPP myocardial imaging. To reveal the clinical efficacy of 123I-BMIPP SPECT, 20 patients with vasospastic angina were studied using resting, 3-hour delayed image with 123I-BMIPP and exercise, 3-hour delayed image with 201Tl SPECT. 123I-BMIPP uptake was decreased compared to 201Tl (discordant) in 12 patients (60%) and in 49/100 myocardial segments (49%). The extent and severity score in resting image with 123I-BMIPP were significantly larger than that in delayed image with 201Tl (p < 0.01). In 123I-BMIPP SPECT, the severity score in the latest ischemia were significantly larger than that in others. The incidence of a complete agreement of decreased 123I-BMIPP uptake and coronary artery spasm was significantly higher (75%) than that in 201Tl (28%, p < 0.01). Furthermore, compared to 201Tl uptake, decreased 123I-BMIPP uptake much more corresponded to reduced wall motion in 9 of patients with mismatching. The severity of regional wall motion abnormality was significantly correlated with severity score of 123I-BMIPP. Late redistribution in delayed image with 123I-BMIPP was seen in 6 patients. The regional washout rate and the severity of regional wall motion abnormality in 6 patients was significantly lower than that in others (p < 0.05). Thus, metabolic abnormality assessed by 123I-BMIPP is well associated with left ventricular asynergy and spastic region in patients with vasospastic angina. In conclusion, 123I-BMIPP SPECT may sensitively delineate the impaired myocardium following coronary artery spasm, and it is very useful in diagnosing and estimating the severity of vasospastic angina.     

Effect of immunosuppression on composition of quasispecies population of hepatitis C virus in patients with chronic hepatitis C coinfected with human immunodeficiency virus

BACKGROUND/AIMS: To study the effects of the immunosuppression caused by the reduction of CD4 activity on the composition of hepatitis C virus (HCV) populations, we analyzed the number of HCV quasispecies clones and the nucleotide diversity of the hypervariable region 1 (HVR1) of HCV in 37 patients with hemophilia with persistent HCV infection, with or without human immunodeficiency virus (HIV). METHODS: The numbers of HCV quasispecies clones were measured by fluorescence single-strand conformation polymorphism analysis. Direct sequencing was used to analyze the degree of diversity of HVR1. We compared these values according to coinfection with HIV, and CD4 counts of patients. RESULTS: There were no differences in either the number of HCV clones or the diversity between patients with and without HIV coinfection. In HIV coinfected patients the diversity decreased in association with the decrease in CD4 count while the number of HCV clones did not. The diversity of HVR1 was 3.64 +/- 5.03% in patients with a CD4 count < 50/microliters and 14.92 +/- 6.03% in patients with a CD4 count > or = 50/microliters; it was significantly lower in the former (p = 0.0002). CONCLUSIONS: A severe reduction in the CD4 count, which is considered to cause a decline in the activity of helper T-lymphocytes, induced changes in the composition of HCV populations; one or a few quasispecies clones are predominant in the HCV population in the serum of individual patients.