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.     

Specific changes in human brain following reperfusion after cardiac arrest

BACKGROUND AND PURPOSE: Very few reports are available on serial changes in human brain after cardiac arrest. The primary objective of this study is to investigate sequential neuroradiological changes in patients remaining in a persistent vegetative state following resuscitation after cardiac arrest. METHODS: We repeatedly studied eight vegetative patients resuscitated from unexpected out-of-hospital cardiac arrest using computed tomographic (CT) scanning and high-field magnetic resonance (MR) imaging at 1.5 T. RESULTS: In seven of the eight patients, CT scans obtained between days 2 and 6 features symmetrical low-density lesions in the bilateral caudate, lenticular, and/or thalamic nuclei. These ischemic lesions were persistently of low density on serial CT scans. In these seven patients, MR images demonstrated what were thought to be hemoglobin degradation products derived from minor hemorrhages localized in the bilateral basal ganglia, thalami, and/or substantia nigra. Diffuse brain edema in the acute stage and diffuse brain atrophy in the chronic stage were consistent neuroradiological findings. No abnormal enhanced lesions were demonstrated by CT scans. CONCLUSIONS: The most characteristic findings on high-field MR images were symmetrical lesions in the bilateral basal ganglia, thalami, and/or substantia nigra with specific changes suggestive of minor hemorrhages that were not evident on CT scans. We speculate that these minor hemorrhages result from diapedesis of red blood cells in these regions during the reperfusion period through the endothelium disrupted by ischemia-reperfusion insult.     

Prolonged exposure to intravesical foreign body induces a giant calculus with attendant renal dysfunction

A 31-year-old man came to our hospital complaining of severe voiding pain. He had inserted a fishing line made of nylon into his urethra at the age of eighteen, which was unable to be taken out and had been left there for 13 years. Preoperative ultrasonogram showed severe bilateral hydronephrosis and the serum BUN and creatinine level were as high as 45.2 mg/dl and 4.8 mg/dl, respectively. A huge bladder stone was demonstrated in X-ray film, the patient was admitted and vesicolithotomy was performed. The size of the stone was 10.5 x 7.5 x 7.5 cm and the weight was 360 grams. The fishing line was found inside the stone and the length was over 3 meters. The serum BUN and creatinine level after the operation were still high as 28.4 mg/dl and 4.1 mg/dl, respectively, and they did not improve even after six months following.     

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.     

Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.     

Comparison of surgically attached and non-attached repair of the rat Achilles tendon-bone interface. Cellular organization and type X collagen expression

The effects of surgical repair versus non-repair on cell morphology and type X collagen expression were investigated using a rat model of Achilles tendon avulsion. The animals were divided into four groups. In Group 1, tendon was reattached to the original attachment site by suturing through a drill hole in the calcaneus; in Group II, tendon was not reattached and a drill hole was not made; in Group III, tendon was not reattached but a drill hole was made; and the animals in Group IV were sham operated. In Group I (tendon reattached), at 2 weeks postoperatively, many hypertrophic chondrocytes appeared at the reattachment site adjacent to bone and type X collagen was detected immunologically both in the cells and in the extracellular matrix. After 4 weeks, the cells at the original site of attachment were arranged in rows along the newly formed tendon fibers and were stained with type X collagen antibody. By contrast, when tendon was not reattached (Groups II and III), a gap between the original attachment site and the tendon stump was observed through the entire postoperative period. At 8 weeks, the original attachment site was covered by fibrocartilaginous tissue and tendon became attached to the calcaneal fibrocartilage area, which is proximal to the original attachment site. Type X collagen was detected in the cells which were adjacent to bone. In Group IV (sham operation), there were no changes in histology or type X collagen distribution, either at the attachment site or in tendon and bone, compared with the non-operated control rats. These results suggest that surgical reattachment of tendon to the original site is important to help reorganize cells during the repair process. Type X collagen was identified immunohistochemically in the cells adjacent to bone in all the groups, suggesting that it may play a role in maintaining distinct areas of calcified and non-calcified fibrocartilage.     

Numerical simulation of parallel-plate particle separator for estimation of charge distribution of PM2.5

A numerical simulation of an instrument that is used to measure the charging state of PM2.5 is conducted in order to clarify its measurement uncertainty and to improve its performance. The instrument, a parallel-plate particle separator (PPPS), is designed to classify aerosol particles according to their charging states and measure their quantities. The trajectories of submicron particles in the PPPS are numerically analyzed using the Lagrangian particle tracking method, taking into account the Brownian force and the electrostatic force. First, it is confirmed that the deterioration in the classification accuracy observed in the experiment is due to Brownian diffusion. The optimal condition that improves the accuracy is investigated through a parametric study by varying the balance of flow rates at the inlets, the geometry of the inlet and exit sections, and the applied voltage. It is found that decreasing the flow rate of the central inlet for aerosol or narrowing the central inlet improves the accuracy. The dependence of the accuracy on the flow rate is found to be in accordance with the experimental results. For charged particles, an optimum voltage that maximizes the classification accuracy is found. On the basis of the simulation results, we propose a method to determine the charge distribution of aerosol from the number of particles counted at each exit of the PPPS. In the test assuming aerosol in the air, the charge distribution determined from the number count at the exits is found to perfectly agree with the charge distribution specified at the inlet.

Copyright © 2019 American Association for Aerosol Research     

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