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.     

Phase diagrams calculated for Fe-rich Fe-Si-Co and Fe-Si-Al ordering alloy systems

Theoretical analysis based on the calculation of phase diagrams was employed for Fe-Si-Co and Fe-Si-Al ordering systems to clarify the necessity for the occurrence of phase separation in Fe-base ternary ordering systems. The free energy of Fe-base ternary ordering alloys where B2 and D0₃ ordered structures are formed is evaluated statistically using a pairwise interaction approximation up to second nearest neighbours, taking into account not only the atomic interaction but also the magnetic interaction, based on the Bragg-Williams-Gorsky model. The calculated phase diagrams are consistent with the experimentally obtained ones. The phase diagram calculation in this work is useful to predict the equilibrium states of the ternary ordering systems. The phase separation in ordering alloys is caused by the contribution of excess free energies due to ordering. The influences of ferromagnetism on the two-phase regions are also demonstrated.     

Two patients with polymyositis or dermatomyositis complicated with massive pleural effusion

Two patients with polymyositis (PM) or dermatomyositis (DM) complicated with massive pleural effusion are reported here. Both patients presented a high-grade fever, pleural effusion prominent on the right, and good response to steroid therapy. In a 50-year-old woman with PM, combined process of pleural inflammation, cardiomyopathy and coexisting hypothyroidism were considered to be responsible for the accumulation of the massive pleural effusion. However, in a 34-year-old man with DM, pleural inflammation associated with interstitial pneumonia or pleural microvasculopathy in DM was considered to be responsible for the accumulation of the massive pleural effusion.     

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.     

Technique for anisotropic extension of organic crystals: application to temperature dependence of electrical resistance

We have developed a technique for the anisotropic extension of fragile molecular crystals. The pressure medium and the instrument, which extends the pressure medium, are both made from epoxy resin. Since the thermal contraction of our instrument is identical to that of the pressure medium, the strain applied to the pressure medium has no temperature dependence down to 2 K. Therefore, the degree of extension applied to the single crystal at low temperatures is uniquely determined from the degree of extension in the pressure medium and thermal contractions of the epoxy resin and the single crystal at ambient pressure. Using this novel instrument, we have measured the temperature dependence of the electrical resistance of metallic, superconducting, and insulating materials. The experimental results are discussed from the viewpoint of the extension (compression) of the lattice constants along the parallel (perpendicular) direction.     

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.     

Alterations in antioxidant status of rats following intake of ginger through diet

Ginger is known to possess potent antioxidant and anti-inflammatory properties. Therefore, in vivo studies in rats were initiated to investigate if ginger fed through diet can improve their antioxidant status. Inbred male Wistar/NIN rats were divided into four groups containing six animals per group. The 1st group received a stock diet whereas the 2nd, 3rd and 4th groups were fed with a diet incorporating ginger powder at 0.5%, 1% and 5% levels for a period of one month. After one month of feeding, rats were sacrificed and their livers and kidneys collected for the analysis of antioxidant enzymes like superoxide dismutase (SOD), catalase and glutathione peroxidase (GSHPx), and to estimate lipid peroxidation and protein oxidation. The levels of all the three enzymes, which are the important components of antioxidative defenses, were significantly stimulated in the livers of groups fed with ginger. The significant reduction in lipid peroxidation in livers and kidneys and inhibition of protein oxidative products in livers indicated the antioxidant potential of ginger when consumed naturally through diet. The findings reported suggest that regular intake of ginger through diet can protect against oxidative tissue damage.