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.     

Subarachnoid haemorrhage induced proliferation of leptomeningeal cells and deposition of extracellular matrices in the arachnoid granulations and subarachnoid space. Immunhistochemical study

Subarachnoid haemorrhage (SAH) often leads to subarachnoid fibrosis and resultant normal pressure hydrocephalus; however, how subarachnoid fibrosis occurs is unknown. We examined the changes within arachnoid granulations (AGs) and the subarachnoid space (SAS) chronologically at the parasagittal region obtained from patients with SAH at autopsy and made comparison with controls by immunostaining for cytokeratin, specific marker for leptomeningeal cells and by the elastica Masson-Goldner methods. Within a week some AGs were torn, and many inflammatory cells filled the AGs and SAS. Cytokeratin positive cells were scarce. During the next two weeks cytokeratin positive cells increased. After three weeks, AGs and SAS were filled by dense deposits of extracellular matrices surrounded by multiple layers of leptomeningeal cells.     

The formation or the reduction of a disulfide bridge on the gamma subunit of chloroplast ATP synthase affects the inhibitory effect of the epsilon subunit

We have studied the change of the catalytic activity of chimeric complexes that were formed by chloroplast coupling factor 1 (CF1) -gamma, alpha and beta subunits of thermophilic bacterial F1 after formation or reduction of the disulfide bridge of different gamma subunits modified by oligonucleotide-directed mutagenesis techniques. For this purpose, three mutant gamma subunits were produced: gamma Delta194-230, here 37 amino acids from Pro-194 to Ile-230 are deleted, gammaC199A, Cys-199 is changed to Ala, and gamma Delta200-204, amino acids from Asp-200 to Lys-204 are deleted. All of the chimeric subunit complexes produced from each of these mutant CF1-gamma subunits and alpha and beta subunits from thermophilic bacterial F1 lost the sensitivity against thiol reagents when compared with the complex containing wild-type CF1-gamma. The pH optimum (pH 8.5-9.0) and the concentration of methanol to stimulate ATPase activities were not affected by these mutations. These indicate that the introduction of the mutations did not change the main features of ATPase activity of the chimeric complex. However, the interaction between gamma subunit and epsilon subunit was strongly influenced by the type of gamma subunit itself. Although the ATPase activity of the chimeric complex that contained gamma Delta200-204 or gammaC199A was inhibited by the addition of recombinant epsilon subunit from CF1 similarly to complexes containing the reduced wild-type gamma subunit, the recombinant epsilon subunit did not inhibit the ATPase of the complex, which contained the oxidized form of gamma subunit. Therefore the affinity of the epsilon subunit to the gamma subunit may be dependent on the state of the gamma subunit or the epsilon subunit may bind to the oxidized form of gamma subunit in a mode that does not inhibit the activity. The ATPase activity of the complex that contains gamma Delta194-230 was not efficiently inhibited by epsilon subunit. These results show that the formation or reduction of the disulfide bond on the gamma subunit may induce a conformational change in the region that directly affects the interaction of this subunit with the adjacent epsilon subunit.     

Mechanochemically synthesized ZIF-8 nanoparticles blended into 6FDA-TrMPD membranes for C3H6/C3H8 separation

The mixed matrix membranes (MMMs) consisting zeolitic-imidazolate framework-8 (ZIF-8) nanoparticles in a polymer have been of considerable interest in separation applications. The fillers used are mostly synthesized using the solvothermal method. In this study, the ZIF-8 nanoparticles were synthesized using a solvent-less and salt-free mechanochemical method and were added to 6FDA-TrMPD polyimide to prepare MMMs. The single gas permeation of C₃H₆ and C₃H₈ through the MMMs was investigated. The C₃H₆ permeability and C₃H₆/C₃H₈ ideal selectivity of a 20 wt% mechano-synthesized ZIF-8/6FDA-TrMPD MMM were 70% and 32% higher than those of the neat polymer membrane at 0.1 MPa and 308 K, respectively. The C₃H₆/C₃H₈ separation performance of the mechano-synthesized ZIF-8 MMM was similar to that of the conventional solvothermal-synthesized ZIF-8 MMM. This separation performance was in good agreement with the Maxwell model. Temperature and pressure dependence analyses confirmed that the mechano-synthesized ZIF-8 nanoparticles acted as molecular sieves in the MMMs for the C₃H₆ and C₃H₈ permeation.     

Microdosimetric specification of the radiation quality of a d(48.5)+Be fast neutron therapy beam produced by a superconducting cyclotron

The proportional counter microdosimetric technique has been employed to quantify variations in the quality of a d(48.5)+Be fast neutron beam passing through a homogeneous water phantom. Single event spectra have been measured as a function of spatial location in the water phantom and field size. The measured spectra have been separated into component spectra corresponding to the gamma, recoil proton and alpha plus heavy recoil ion contribution to the total absorbed dose. The total absorbed dose normalized to the "monitor units" used in daily clinical use has been calculated from the measured spectra and compared to the data measured with calibrated ion chambers. The present measurements agree with the ion chamber data to within 5%. The RBE of the neutron beam is assumed to be proportional to the microdosimetric parameter y* for the dose ranges pertinent to fractionated neutron therapy. The relative variations in y*, assumed to be representative of variations in the RBE are mapped as a function of field size and spatial location in the phantom. A variation in the RBE of about 4% for points within and 8% for points outside a 10 cm x 10 cm field is observed. The variations in the RBE within the beam are caused by an increase in the gamma component with depth. An increase in the RBE of about 4% is observed with increasing field size which is attributed to a change in the neutron spectrum. Compared to the uncertainties in the prescribed dose, associated with uncertainties in the clinically used RBE, variation in the RBE between various tissues, and other dosimetric uncertainties caused by factors such as patient inhomogeneities, patient setup errors, patient motion, etc., the measured spatial RBE variations are not considered significant enough to be incorporated into the treatment planning scheme.     

Proteome of human endometrium: Identification of differentially expressed proteins in proliferative and secretory phase endometrium

Purpose: To exploit the potential of proteomics to identify and study additional yet‐unidentified important proteins present in human endometrium. Experimental design: The proteome of human endometrium would be established using 2‐DE and MALDI and the data analyzed to identify differential protein expression in the proliferative and secretory phase of the menstrual cycle using PDQuest software and MALDI. Results: In the present work, 2‐DE of human endometrium protein led to the resolution of over 200 spots. Subsequent MALDI analysis of 215 spots allowed the identification of 194 proteins. A total of 57 out of the 215 spots were found to be differentially expressed, out of which 49 could be identified using MALDI. These differentially expressed proteins included structural proteins, molecular chaperones, signaling proteins, metabolic proteins, proteins related to immunity, RNA biogenesis, protein biosynthesis and others. The differential expressions of seven representative proteins in secretory and proliferative phase endometrium tissue were confirmed by immunoblot analysis. Conclusion and clinical relevance: This study establishes the 2‐D proteome of human endometrium represented by 194 identified protein spots. The present data provides an important clue towards determining the function of these proteins with respect to endometrium related diseases.     

Wide Color Variation in SiNO Thin Films Dispersed with Precipitated TiN Nano Particles

Amorphous thin films of Ti_1?ySi_y(N,O) with y ≥ 0.38 were prepared by reactive sputter deposition in a nitrogen atmosphere. Thermal annealing of the films in an ammonia flow above 800°C yielded Si(N,O) amorphous thin films dispersed with precipitated TiN nanosized particles. The film color changed with Si content y and the annealing conditions, from carrot orange to cream yellow in the as‐deposited films due to their oxynitride nature, and from dark green to canary yellow and from iron blue to horizon blue at respective annealing temperatures of 800°C and 900°C due to metallic nature of the TiN nanosized particles precipitated in the annealing.     

Dose-dependent effect in the inhibition of oxidative stress and anticlastogenic potential of ginger in STZ induced diabetic rats

Ginger is an important medicinal herb has numerous bioactive components and is used in the management, control and/or treatment of diseases including diabetes mellitus. The present study was undertaken to see the dose–response effect of ginger and evaluate the possible protective effects of dietary ginger on oxidative stress and genotoxicity induced by streptozotocin (STZ) diabetic rats. Inbred male Wistar/NIN rats of 8–9 weeks old were treated with 30 mg/kg of STZ. Rats were divided into different groups of control, diabetic non-treated, and diabetic treated with ginger powder at 0.5%, 1% and 5% respectively. After feeding for a month, blood and tissues were collected to see the effect of ginger on antioxidant status, DNA damage and bone marrow genotoxicity. In this study ginger exerted a protective effect against STZ-induced diabetes by modulating antioxidant enzymes and glutathione and down regulating lipid and protein oxidation and inhibition in genotoxicity in a dose–response manner.     

Additive Sintering,Postannealing, and Dielectric Properties of SrTaO2N

The maintaining of the chemical composition and electrical insulativity of SrTaO₂N ceramics was investigated during sintering and annealing, using powders prepared by the nitridation of Sr₂Ta₂O₇. Due to the low thermal stability of SrTaO₂N, the partial loss of SrO and nitrogen induced the formation of a TaO_0.9 impurity after heat‐treating at above 1100°C. The sintering additive SrCO₃ and postannealing in NH₃ were employed to compensate for the loss of SrO and nitrogen to obtain ceramics with the original chemical composition. The as‐sintered SrTaO₂N ceramics with various relative density (RD) were annealed in NH₃ to observe the recovery of color and electrical insulativity. It was found that the inner part of the well‐sintered samples with RD = 95.1% could not be recovered by annealing, and continued to exhibit semiconducting behavior and a black color. On the other hand, for the as‐sintered SrTaO₂N ceramics with RD < 84%, both the nitrogen content and electrically insulating behavior were completely recovered after annealing. The postannealed SrTaO₂N ceramics (RD = 83.3%) possessed a relatively large dielectric constant of 450 with a low dielectric loss of less than 0.1 at 100 Hz, almost independent of frequency and temperature.