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.     

Mechanisms of orientational and photoelastic birefringence generation of methacrylates for the design of zero–zero‐birefringence polymers

The intrinsic birefringence Δn⁰ and photoelastic coefficient C of poly(methyl methacrylate), poly(2,2,2‐trifluroethyl methacrylate), poly(phenyl methacrylate), and poly(2,2,3,3,3‐pentafluorophenyl methacrylate) were determined. We categorized these methacrylate polymers into four birefringence‐types, even though their molecular structures differed only by the substituents on the side chains. Based on the results of Δn⁰ and C, novel polymers that exhibit neither orientational nor photoelastic birefringence, i.e., zero–zero‐birefringence polymers, were designed and synthesized by quaternary copolymerization system. Furthermore, we confirmed that the mechanisms of orientational birefringence and photoelastic birefringence generation were different in these methacrylate polymers. The conformation of the repeat unit of the polymers was nearly constant during the generation of orientational birefringence. In contrast, the conformation of the repeat unit of the polymers changed during the generation of photoelastic birefringence in the glassy state. These findings demonstrated the reasonability of evaluating orientational and photoelastic birefringence separately, as well as the adequacy of the classification of polymers into four birefringence‐types. Given these results and the fact that zero–zero‐birefringence polymers could be prepared successfully by four‐birefringence type monomers, we demonstrated the reasonability of the method for designing the zero–zero‐birefringence polymers. POLYM. ENG. SCI., 55:1330–1338, 2015. © 2015 Society of Plastics Engineers     

Changes in the gaseous H2S barrier properties of damaged silicate coated nylon 6 films

The damage imposed on SiO _x deposited nylon 6 films as a result of abrasion with a cotton cloth and Gelboflex testing was examined by evaluating the rate at which copper plates, which were enveloped by the damaged films, were corroded by H₂S. Abrasion with a cotton cloth caused some micro-cracking of the SiO _x layer and the permeation rate of H₂S approached that of the uncoated nylon 6 film. Damage to the SiO _x layer by twisting and crushing progressed gradually with the number of Gelboflex test cycles and correspondingly the corrosion rate of the copper plates increased. Comparison of the corrosion rates of the copper plates kept in the pouches made of various commercial films with those obtained for the damaged SiO _x deposited nylon 6 films showed a clear relationship between the H₂ permeation rate of the films and the corrosion rate of the copper plates by H₂S.     

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.     

Satoyoshi's syndrome in an adult: a review of the literature of adult onset cases

Satoyoshi syndrome consists of painful intermittent muscle spasms, alopecia and diarrhea. The age of onset is commonly less than 20 years of age. Adult onset of this syndrome is rare. We report a 65-year-old Japanese woman with Satoyoshi's syndrome of adult onset. Satoyoshi's syndrome of adult onset shows no skeletal abnormalities, in comparison with the classical pediatric cases. The clinical features in our patient revealed the benign and long-term course of muscle spasm and alopecia. This progression differed markedly from the other patients of adult onset. Thus, the severity of Satoyoshi's syndrome is variable in adult onset cases, and this diagnosis should be considered in adults with various and unexplained muscle spasms.     

Augmentation by phthalimides of phorbol ester-induced expression of tumor necrosis factor alpha message

N(alpha)-Phthalimidoglutarimide (thalidomide), 2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (PP-33) and its 4,5,6,7-tetrafluoro derivative (FPP-33) augmented 12-O-tetradecanoylphorbol 13-acetate-induced production by human leukemia HL-60 cells of both tumor necrosis factor alpha (TNF-alpha) mRNA and secreted TNF-alpha protein. Intracellular TNF-alpha protein production was increased to a lesser extent.