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.     

Biodegradation of poly(lactic acid)—cassava bagasse composites produced by injection molding

Neat poly (lactic acid) (PLA) and PLA/cassava bagasse (CB) composites were used to produce seedling tubes by extrusion and injection molding. The tubes were buried in simulated soil, and their biodegradation was investigated by weight loss, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). After 180 days, the composites' biodegradation was higher than neat PLA material, and the higher the CB content, the higher the biodegradation, which caused fissures and voids in the material. The biodegradation of PLA/CB composites increased the phosphorus content in the soil after 180 days. Composites of PLA with CB, an abundant agro-industrial residue in Brazil, are promising because they can reduce the environmental impact due to CB's proper destination, and the composites' costs and biodegradation are faster than pure PLA material. Both the faster biodegradation of the tube and the higher P content are advantageous for seedling tubes.     

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.     

Suitable fixation condition for rat liver using microwave irradiation and its application to the immunohistochemistry of glutamate dehydrogenase

In 50 patients auditory threshold and brain stem evoked potential studies were carried out before and after myelography. Due to the analysis of amplitudes and latencies of auditory brain stem measurements, significant functional disorders of the hearing organ and the auditory pathway could be demonstrated. In most of the patients these functional disorders were found to be subclinical, whereas 12 patients showed alterations extending from a subjectively slight hearing loss to an audiometrically objectified acute hearing loss depending on its intensity in each case. The reasons of these functional disorders could not be clarified. An open cochlear aqueduct through which perilymph enters the subarachnoidal space leading to a secondary endolymphatic hydrops can be considered as the cause in cases where manifest symptoms develop. The changes in brain stem audiometry can be additionally explained by changes in osmolality of the inner ear fluids which may lead to the development of an endolymphatic hydrops.     

Erythroid potentiating activity of tissue inhibitor of metalloproteinases on the differentiation of erythropoietin-responsive mouse erythroleukemia cell line, ELM-I-1-3, is closely related to its cell growth potentiating activity

The erythroid-potentiating activity (EPA) of the tissue inhibitor of metalloproteinase-1 (TIMP-1) was re-examined using ELM-I-1-3, a mouse erythroleukemia cell line, which responded well to erythropoietin. Depletion of pre-existing TIMP-1 from fetal calf serum in culture medium using monoclonal antibody suppressed erythropoietin-induced differentiation as measured by the induction of hemoglobin, commitment assay and globin mRNAs. The removal of TIMP-1 also suppressed the proliferation of ELM-I-1-3 as measured by cell number and de novo DNA synthesis. These changes were reversed by the addition of purified TIMP-1 to the culture medium. Anti-TIMP-1 antibody also blocked both hexamethylene bisacetamide (HMBA)-induced erythroid differentiation and the proliferation of both ELM-I-1-3 and Friend erythroleukemia cells. Considering previous reports analyzing the chemical induction of Friend mouse erythroleukemia cell differentiation, our results suggest that erythropoietin- or HMBA-induced erythroid differentiation might also be coupled with cell proliferation. Our 3H thymidine-uptake experiment shows that TIMP-1 removal was also effective in the inhibition of cell growth of various other cell lines in addition to erythroleukemia cell lines. These results suggest that EPA action of TIMP-1 on erythroid leukemia cell lines is closely related to its activity to promote the cell growth of various cell lines and cells including erythroleukemia cell lines.     

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.