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.     

The effect of spin fluctuations on thermal properties in strongly correlated fermion systems

The effect of spin fluctuations on the thermal properties of strongly correlated itinerant fermion systems is discussed based on the self-consistent renormalized (SCR) spin fluctuation model. Specific heat and magnetic susceptibility in the normal phase of liquid-³He and heavy electron compounds at finite temperatures are well described by the unified SCR picture including the mode-mode coupling of spin fluctuations beyond the random phase approximation (RPA).     

Development of 170 GHz/500 kW gyrotron

A development of 170GHz/500kW level gyrotron was carried out as R&D work of ITER. The oscillation mode is TE_31,8. In a short pulse experiment, the maximum power of 750kW was achieved at 85kV/40A. The efficiency was 22%. In the depressed collector operation, 500kW/36%/50ms was obtained. The maximum efficiency of 40% was obtained at P_RF=470kW whereas the power decrease by the electron trapping was observed. Pulse extension was done up to 10s at P_RF=170kW with the depressed collector operation. The power was limited by the temperature increase of the output window.     

Evidence that angiotensin II, endothelins and nitric oxide regulate mitogen-activated protein kinase activity in rat aorta

We measured the activity of mitogen-activated protein (MAP) kinases, enzymes believed to be involved in the pathway for cell proliferation, in rat aortic strips with or without endothelium, and examined effects of angiotensin receptor antagonists, endothelin receptor antagonists and nitric oxide (NO)-related agents. Endothelium removal produced an activation of MAP kinase activity in the strips, whereas the enzyme activity was not affected in the adventitia. The MAP kinase activation was inhibited by either the angiotensin AT1 receptor antagonist losartan or the endothelin ETA receptor antagonist BQ 123. The combination of both antagonists caused an additive inhibition. The angiotensin AT2 receptor antagonist PD 123,319 and the endothelin ETB receptor antagonist BQ 788 did not affect the MAP kinase activation. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) caused an activation of MAP kinase in the endothelium-intact aorta and the MAP kinase activation was inhibited by losartan or BQ123. The NO releaser nitroprusside inhibited the MAP kinase activation induced by endothelium removal or angiotensin II. These results suggest that even in isolated arteries, NO of endothelial origin tonically exert MAP kinase-inhibiting effects and endogenous angiotensin II and endothelins in the media are tonically released to cause MAP kinase-stimulating effects in medial smooth muscle.     

Acrylic nonaqueous dispersion using butylated melamine-formaldehyde resin as dispersant

A series of acrylic nonaqueous dispersions were prepared by using various kinds of butylated melamine–formaldehyde (BMF) resins as dispersant. The functional group composition of BMF to form stable dispersion was butoxy group more than 13 mol/BMF 1 mol, and methylol group ranged from 1 to 2.5 mol/BMF 1 mol. It is concluded that the anchoring of BMF to acrylic copolymer was due to the formation of covalent bond between methylol group in BMF and hydroxy group in acrylic copolymer.     

A thermomechanical investigation of highly cold-drawn polycarbonate

A new technique detecting molecular motions in drawn polymers was applied to highly cold-drawn polycarbonate of bisphenol A. It is shown that the sample exhibits thermal shrinkage in three steps with the temperature increase up to above the glass transition temperature. The molecular relaxation at the highest temperature is due to the glass transition. The other two molecular motions at the lower temperature are those of main chain in the glassy state and they correspond to the molecular motions as revealed in dielectric measurement by Sacher.¹ By using the general theory of the thermal analysis by Ozawa,² the apparent activation energies of these molecular motions were obtained: for the highest temperature 110 kcal/mole, and for the lowest temperature, 33.5 kcal/mole. The impact strength and the cold workability of this polymer are also discussed in relation to these molecular motions.     

The relationship between the molecular weight and the critical miscibility composition of a solvent-nonsolvent-terpolymer system

A theoretical equation for the dependence of the apparent molecular weight measured by light scattering on the solvent used has been derived with regard to the composition heterogeneity. Terpolymers corresponding to a partial azeotrope were synthesized from styrene, acrylonitrile, and methyl methacrylate with mole fractions of 0.55, 0.16, and 0.29, respectively. The molecular weight measured by light scattering was found to be independent of the solvent used. Therefore the terpolymer was concluded to be apparently homogeneous in composition. The relationship between the molecular weight M of the terpolymer and the volume fraction of the nonsolvent γ in the solvent mixture at the precipitation point in a butanone-methanol-terpolymer system was experimentally proved to follow the equation where γ₀ and b′ are constants. Between the molecular weight and the limiting viscosity number [η] of the terpolymer the following relationships are valid at 35°C: and      

Thermodynamic investigations of liquid Bi-Na and Sn-Na alloys by coulometric titration using β″-alumina

The following double galvanic cell was assembled and the thermodynamic properties of liquid Bi-Na and Sn-Na alloys, and the ion selectivity of -alumina during coulometric titration, were investigated. Mo, Na(I)¦-alumina¦M-Na(I), Mo [I] M-Na(I)¦-alumina¦Au + Au₂Na, Mo [II] (M = Bi or Sn) where M-Na(1) and Au + Au₂Na were used as the common electrode and reference electrode, respectively. Sodium was coulometrically titrated through the -alumina electrolyte of cell I both ways, and the EMFs were measured. It was found that no ion-exchange reaction occurs between the liquid alloys and the -alumina, and only Na was transferred in the -alumina during coulometric titrations. The thermodynamic properties of liquid Sn-Na and Bi-Na alloys were found to be in agreement with the literature.     

Development of flexible displays using back‐channel‐etched In–Sn–Zn–O thin‐film transistors and air‐stable inverted organic light‐emitting diodes

We developed flexible displays using back‐channel‐etched In–Sn–Zn–O (ITZO) thin‐film transistors (TFTs) and air‐stable inverted organic light‐emitting diodes (iOLEDs). The TFTs fabricated on a polyimide film exhibited high mobility (32.9 cm²/Vs) and stability by utilization of a solution‐processed organic passivation layer. ITZO was also used as an electron injection layer (EIL) in the iOLEDs instead of conventional air‐sensitive materials. The iOLED with ITZO as an EIL exhibited higher efficiency and a lower driving voltage than that of conventional iOLEDs. Our approach of the simultaneous formation of ITZO film as both of a channel layer in TFTs and of an EIL in iOLEDs offers simple fabrication process.