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.     

Three-dimensional display of the bronchi using helical CT

The purpose of this study was to evaluate the clinical usefulness of three-dimensional (3D) images of the bronchi obtained using helical CT. Thirteen patients with lung cancer, one with tracheal diverticulum, and one with bronchial amyloidosis were examined. The CT scanner employed was the Toshiba Xforce. The helical CT scan cycle consisted of 20 continuous rotations, each requiring 1.5 sec, for a total scanning time of 30 sec. Scans were obtained using a 5-mm X-ray beam width, a 5-mm/1.5 sec couchtop sliding speed, and a 2-mm reconstruction interval. 3D images were reconstructed using a CEMAX VIPstation. The optimal lower and upper threshold CT values for 3D images of the bronchi were -650 and -100 HU, respectively, and 3D images clearly depicted endobronchial lesions. Cartilage crescents were also demonstrated, but longitudinal and circular mucosal folds could not be visualized. In conclusion, 3D images of the bronchi acquired using helical CT were useful in evaluating endobronchial lesions.     

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.     

Induced-fit association between DNA and esperamicin. Importance of structural flexibility in host DNA duplex

In this study, a series of synthetic oligonucleotide duplexes are tested as a substrate for esperamicin. The duplexes contain a typical binding sequence of esperamicin, 5'-GGA/TCC, but have different flexibilities in helix structure from each other. When cleavage activities of these oligonucleotides by esperamicin were estimated by using DNA sequencing method, a substantial increase of the cleavage at 3'-NAGG was observed with increasing the helix flexibility. This observation indicates that structural flexibility of host DNA duplex is important in an induced-fit association between esperamicin and DNA.     

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.     

Improvement in Thermoelectric Characteristics of n-type Iron Disilicide by Local Composition Modification

High thermoelectric figure of merit semiconducting ceramics of n -type iron disilicide with modified local compositions have been developed. Sintering and annealing of the composite powder composed of iron disilicide and precipitated cobalt (II) hydroxide resulted in the dissolution of excess Co and oxygen into the iron disilicide phase. Excess Co segregated to the grain boundary region, while interstitially incorporated oxygen was distributed homogeneously in the microstructure. The maximum figure of merit achieved was 5.2 × 10⁻⁴/K at 673 K.     

Hydrophobic effects on protein/nucleic acid interaction: enhancement of substrate binding by mutating tyrosine 45 to tryptophan in ribonuclease Tl

Hydrophobic effects on binding of ribonuclease Tl to guaninebases of several ribonucleotides have been proved by mutatinga hydrophobic residue at the recognition site and by measuringthe effect on binding. Mutation of a hydrophobic surface residueto a more hydrophobic residue (Tyr45 – Trp) enhances thebinding to ribonucleotides, including mononucleotide inhibitorand product, and a synthetic substrate-analog trinudeotide aswell as the binding to dinucleotide substrates and RNA. Enhancementson binding to non-substrate ribonucleotides by the mutationhave been observed with free energy changes ranging from –2.2 to – 3 .9 kJ/mol. These changes are in good agreementwith that of substrate binding, –2.3 kJ/mol, which iscalculated from Michaelis constants obtained from kinetic studies.It is shown, by comparing the observed and calculated changesin binding free energy with differences in the observed transferfree energy changes of the amino acid side chains from organicsolvents to water, that the enhancement observed on guaninebinding comes from the difference in the hydrophobic effectsof the side chains of tyrosine and tryptophan. Furthermore,a linear relationship between nucleolytic activities and hydrophobicityof the residues (Ala, Phe, Tyr, Trp) at position 45 is observed.The mutation could not change substantially the base specificityof RNase Tl, which exhibits a prime requirement for guaninebases of substrates.     

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.