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.     

Solid-Phase Syntheses of Two Deacetyl-Thymosin β4 Analogues with Substitution at Position 12 and Their Effects on Impaired Blastogenic Response of T Lymphocytes of Uremic Patients

Two deacetyl-thymosin β₄ analogues containing Phe(4Br) or D-Phe(4Br) as position 12 were synthesized by the manual solid-phase method, and their immunological effects on the impaired blastogenic response of phytohemagglutinin-stimulated T lymphocytes of uremic patients with infectious diseases were studied. Bromination of the p-position of Phe¹² resulted in a marked restorative effect on the impaired blastogenic response of T lympocytes compared with that of our synthetic deacetyl-thymosin β₄ The synthetic [Phe(4Br)¹²]deacetyl-thymsin β₄ was approximately equal in potency to our synthetic [Phe(4F)¹²]deacetyl-thymosin β₄ in uremic patients, but the other analogue, [D-Phe(4Br)¹²]deacetyl-thymosin β₄, had no effect.     

Lipid-Lowering Effect of Eriocitrin, the Main Flavonoid in Lemon Fruit, in Rats on a High-Fat and High-Cholesterol Diet

ABSTRACT:  Eriocitrin (eriodictyol 7- O -β-rutinoside) is the main flavonoid in lemon fruit. In this study, eriocitrin was investigated for its lowering effect on serum and hepatic lipids in high-fat and high-cholesterol fed rats. Rats in the control group ( N = 6) were fed a 20% lard and 1% cholesterol diet for 21 d, and rats in the 0.35% eriocitrin group ( N = 6) and 0.70% eriocitrin group ( N = 6) were fed a diet supplemented with eriocitrin 0.35% and 0.70%, respectively. The content of hepatic total cholesterol and triglyceride in the eriocitrin group was no different from that of the control group. The total cholesterol, VLDL+LDL, triglyceride, and phospholipid in the serum of the 0.35% eriocitrin group showed significantly lower concentrations than the control group ( P < 0.05), although there was no difference in the HDL concentrations among the groups. The lowering effect of eriocitrin for serum total cholesterol was thought to be caused by a decrease in VLDL+LDL. The 0.35% eriocitrin group was shown to have a significant increase in excretion of fecal bile acid ( P < 0.05) and a tendency for enhanced hepatic m-RNA levels of LDL receptor in comparison with the control group.     

A new cobalt salicide technology for 0.15-μm CMOS devices

A new cobalt (Co) salicide technology for sub-quarter micron CMOS transistors has been developed using high-temperature sputtering and in situ vacuum annealing. Sheet resistance of 11 Ω/□ for both gate electrode and diffusion layer was obtained with 5-nm-thick Co film. No line width dependence of sheet resistance was observed down to 0.15-μm-wide gate electrode and 0.33-μm-wide diffusion layer. The high temperature sputtering process led to the growth of epitaxial CoSi ₂ layers with high thermal stability. By using this technology 0.15 μm CMOS devices which have shallow junctions were successfully fabricated     

Contribution of IL-1 beta to the enhancement of Campylobacter rectus lipopolysaccharide-stimulated PGE2 production in old gingival fibroblasts in vitro

Campylobacter rectus is associated with adult periodontitis. We previously reported that C. rectus lipopolysaccharide (LPS)-stimulated prostaglandin E2 (PGE2) production in old cells of human gingival fibroblasts (HGFs) is higher than that in young cells. The present study examined whether an enhancement of C. rectus LPS-stimulated interleukin (IL)-1 beta production in old HGFs contributed to the increased production of PGE2. LPS was prepared from C. rectus ATCC33238. HGFs were established from healthy gingiva in three patients, aged 10-12 years. Cellular aging in culture was determined with increasing doubling. The cultured cells were treated with LPS (0.01-10 micrograms/ml), and the amount of IL-1 beta in the medium was measured after a 24 h incubation. The LPS-stimulated IL-1 beta production in each old cell (corresponding to 57-67% of complete life-span) was increased (1.6-2.6 times) compared to that in the young cells (corresponding to 17-20% of the life-span). The IL-1 beta mRNA synthesis in the presence of LPS in the old cells was higher than that in the young cells. The enhancement of LPS-stimulated PGE2 production was inhibited by anti-IL-1 beta antibody and by IL-1 receptor antagonist. These findings suggest that the greater ability of old cells to produce PGE2 in response to C. rectus LPS is due to their greater level of IL-1 beta.     

Delay time compensation based on coefficient of restitution for collision hybrid motion simulator

A hybrid motion simulator embeds a hardware experiment in a numerical simulation loop. However, it is often subjected to the inherent problem of an energy increase in the collision of two pieces of hardware in a loop because of the delay time. This paper proposes a delay time compensation method based on contact dynamics model for a collision hybrid motion simulator under delay time and establishes a compensation method for coupled translational and rotational motion. The model developed in this paper describes linear uniform motion of a floating object during the period of the delay time until the force and torque are observed and non-linear motion according to environmental stiffness after the initial delay time period in contact. By using the above model, compensation parameters are designed based on desired coefficient of restitution with iterative calculation. The proposed method achieves accurate delay time compensation and simultaneously realizes a variable desired coefficient of restitution over a wide range of frequencies. Furthermore, the compensation method for multi-dimensional motion is established under the assumption that the friction effect is very small. The efficiency of the proposed method is verified through collision experiments for the coupled motion in two dimensions.     

Impregnation of silk sericin into polyester fibers using supercritical carbon dioxide

Silk sericin was impregnated into polyester fabric using supercritical carbon dioxide (SCCO₂) to overcome polyester hydrophobicity. The effects of sericin molecular weight, pH of sericin, solution and cosolvent types on sericin impregnation were investigated. Enzyme‐hydrolyzed, acid‐, based‐hydrolyzed sericin in SCCO₂, and a 30 kDa sericin in SCCO₂ modified with cosolvents such as water, methanol, 1‐propanol, and acetone; and a modifier: sodium hydroxide solution were used in this work. Impregnation of sericin in polyester was indicated by Fourier transform infrared spectrophotometry (FTIR) and dyeing with acid dye. Degradation of polyester fibers during SCCO₂ process was indicated by scanning electron microscopy (SEM). Methylene blue dyeing was used to realize carboxyl group in polyester. The results showed no impregnation of sericin into polyester by using SCCO₂ modified with cosolvents. However, sericin was impregnated into modified surface polyester since hydrophilic groups such as carboxyl and hydroxyl groups were regenerated by alkaline hydrolysis. Samples impregnated with hydrolyzed sericin showed high color strength of Supranolechtbordeaux B acid dye. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Discussions of worker ants’ rule-based CHC dealing with changing environments

Contrary to popular belief, biologists discovered that worker ants are really not all hardworking. It has been found that in three separate 30-strong colonies of black Japanese ants (Myrmecina nipponica), about 20% of worker ants are diligent, 60% are ordinary, and 20% are lazy. That is called 20:60:20 rule. Though they are lazy, biologists suggested that lazy worker ants could be contributing something to the colony that is yet to be determined. In our last research, we used CHC (cross generational elitist selection, heterogeneous recombination, and cataclysmic mutation) with the worker ants’ rule (WACHC) aiming at solving optimization problems in changing environments. CHC is a nontraditional genetic algorithm (GA) which combines a conservative selection strategy that always preserves the best individuals found so far with a radical (highly disruptive) recombination operator. In our last research, we verified that WACHC performs better than CHC in only one case of fully changing environment. In this paper, we further discuss our proposed WACHC dealing with changing environment problems with varying degree of difficulty, compare our proposal with hypermutation GA which is also proposed for dealing with changing environment problems, and discuss the difference between our proposal and ant colony optimization algorithms.     

Size adjustment of spherical temperature-sensitive hydrogel beads by liquid–liquid dispersion using a Kenics static mixer

Temperature-sensitive hydrogel beads were prepared by Kenics static mixer technology. The temperature-sensitive monomer N,N-diethylacrylamide and photo-crosslinkable pre-polymer ENT were used as model hydrogel materials. Drop dispersion of high viscosity polymer material in low viscosity hexadecane was made using the static mixer. Drops of a solution of the mixed materials were rapidly photo-crosslinked by UV irradiation after mixing in the static mixer, and spherical hydrogel beads with narrow, normal size distribution were thus prepared. The Kenics static mixer is a useful device for the preparation of spherical beads of temperature-sensitive hydrogels. The Sauter Mean Diameter of the hydrogel beads swollen in deionized water at 293 K was measured. The experimentally determined dimensionless swollen hydrogel bead diameter was well correlated with the Weber number, degree of swelling and viscosity ratio. The effects of gelation and ENT addition on the bead size were evaluated from the degree of swelling. The correlation equation can be used for size adjustment of temperature-sensitive spherical hydrogel beads.