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.     

EFFECT OF DEVELOPER PROPERTIES ON PRINT QUALITY

We investigated the dependence of the toner charge-to-mass ratio (q/m) in a two-component electrophotographic developer on the shaking time, toner concentration (T/C), carrier sizes, and the carrier core and the coating materials, as well as the resulting print qualities in terms of print density, background density, tone reproduction, resolution, and dot gain. Four different sizes of spherical ferrite carriers, four different carrier coating materials, and an irregular iron carrier were used with two types of toner: 14 um red toner (NP-4080) and 8 um cyan toner (CLC-500). The q/m measurement by the blow-off method showed that the red toner charge was positive while the cyan toner charge was negative with these carriers. The toner q/m values, which depended on the shaking time and decreased with the increasing T/C were much more affected by the larger carrier and the smaller toner. The carriers which yielded charges in the proper range produced better print qualities than did the other carriers that yielded a toner q/m     

Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand

Anchietia salutaris tea is traditionally used in Brazil to treat allergies, suggesting it contains compounds with antagonistic activity on the allergic mediators. We have evaluated extracts and semi-purified fractions of Anchietia salutaris as a source of compounds having this type of antagonism on the contraction induced in guinea-pig lung parenchymal strips and on platelet aggregation and shape change. After 10 min pre-incubation dichloromethane extracts containing 30 or 100 microg mL(-1) inhibited the contraction induced by prostaglandin D2 (PGD2) in guinea-pig lung parenchymal strips with dose ratios (DR) of 0.76+/-0.14 and 0.93+/-0.19, respectively; the amount of inhibition depended both on the concentration and on the time of pre-incubation (DR after 30 min pre-incubation was 1.21+/-0.51). The dichloromethane extract and its semi-purified fractions also inhibited the contractions induced by U46619, a more potent, stable, synthetic agonist of thromboxane A2 (TxA2) prostanoid (TP) receptors, the receptors acted upon by PGD2 to produce lung contractions. The dichloromethane extract did not inhibit the lung parenchymal contractions induced by histamine, leukotriene D4 (LTD4) or platelet-activating factor (PAF). Platelet aggregation induced by U46619, adenosine 5'-diphosphate (ADP) or PAF was not inhibited by the dichloromethane extract. Indeed, the extract potentiated platelet aggregation induced by low concentrations of these agonists and also potentiated the shape change induced by U46619. These results imply that the dichloromethane extract of Anchietia salutaris and its semi-purified fractions contain an active principle that competitively inhibits TxA2 TP receptors, the stimulation of which causes lung parenchymal contraction. The inhibition seems to be selective for this receptor subtype, because the extract fails to inhibit platelet aggregation or shape change. This provides additional support of earlier reports suggesting the occurrence of TP receptor subtypes.     

Design and fabrication of RESURF MOSFETs on 4H-SiC(0001), (112~0), and 6H-SiC(0001)

Design and fabrication of lateral SiC reduced surface field (RESURF) MOSFETs have been investigated. The doping concentration (dose) of the RESURF and lightly doped drain regions has been optimized to reduce the electric field crowding at the drain edge or in the gate oxide by using device simulation. The optimum oxidation condition depends on the polytype: N/sub 2/O oxidation at 1300/spl deg/C seems to be suitable for 4H-SiC, and dry O/sub 2/ oxidation at 1250/spl deg/C for 6H-SiC. The average inversion-channel mobility is 22, 78, and 68 cm/sup 2//Vs for 4H-SiC(0001), (112~0), and 6H-SiC(0001) MOSFETs, respectively. RESURF MOSFETs have been fabricated on 10-/spl mu/m-thick p-type 4H-SiC(0001), (112~0), and 6H-SiC(0001) epilayers with an acceptor concentration of 1/spl times/10/sup 16/ cm/sup -3/. A 6H-SiC(0001) RESURF MOSFET with a 3-/spl mu/m channel length exhibits a high breakdown voltage of 1620 V and an on-resistance of 234 m/spl Omega//spl middot/cm/sup 2/. A 4H-SiC(112~0) RESURF MOSFET shows the characteristics of 1230 V-138 m/spl Omega//spl middot/cm/sup 2/.     

Prostaglandin E receptor subtypes in mouse osteoblastic cell line

PGE2 is one of the key molecules in the osteoblast. It is the major prostanoid in the bone, and its production is under the control of both systemic and local factors. PGE2 has been reported to have multiple actions in the osteoblast, such as growth promotion and cell differentiation. To better understand the action of PGE2 in the osteoblast, we determined the PGE receptor subtypes in MC3T3-E1, an osteoblastic cell line derived from the normal mouse calvaria. Northern blot analysis revealed that EP1 and EP4 subtypes are expressed in MC3T3-E1. In contrast, EP3 subtype was not detected by either Northern blot analysis or RT-PCR. The contribution of each subtype was evaluated by studying the effects of subtype-specific analogs on osteoblastic function at confluency and 5 days after confluency. An EP1 agonist, 17-phenyl-omega-trinor PGE2, increased DNA synthesis and decreased alkaline phosphatase activity. 11-Deoxy-PGE1, and EP2 and EP4 agonist, decreased DNA synthesis and increased alkaline phosphatase activity at both stages. Butaprost, an EP2-selective agonist, showed effects similar to those of 11-deoxy-PGE1 only at confluency. Another and more differentiated osteoblastic marker, osteocalcin production, was detectable and was stimulated by 11-deoxy-PGE1 only 5 days after confluency. The exposure of these cells to EP1 agonist changed the cell shape to a more fibroblastic appearance. These results indicate that EP1, EP4, and probably EP2 are present in MC3T3-E1 cells; EP1 promotes cell growth, and EP2 and EP4 mediate differentiation of the osteoblast. Furthermore, the decreased response to EP2-specific agonist 5 days after confluency suggests that the expression of PGE receptor subtype is dependent on the stage of osteoblastic differentiation. This is the first report to determine PGE receptor subtypes in the bone.     

Survey of switching techniques in high-speed networks and their performance

One of the most promising approaches for high speed networks for integrated service applications is fast packet switching, or ATM (asynchronous transfer mode). ATM can be characterized by very high speed transmission links and simple, hard-wired protocols within a network. To match the transmission speed of the network links, and to minimize the overhead due to the processing of network protocols, the switching of cells is done in hardware switching fabrics in ATM networks. A number of designs have been proposed for implementing ATM switches. Although many differences exist among the proposals, the vast majority of them are based on self-routeing multistage interconnection networks. This is because of the desirable features of multi-stage interconnection networks such as self-routeing capability and suitability for VLSI implementation. Existing ATM switch architectures can be classified into two major classes: blocking switches, where blockings of cells may occur within a switch when more than one cell contends for the same internal link, and non-blocking switches, where no internal blocking occurs. A large number of techniques have also been proposed to improve the performance of blocking and non-blocking switches. In this paper, we present an extensive survey of the existing proposals for ATM switch architectures, focusing on their performance issues.     

Periacinar collagenization in patients with chronic alcoholism

To examine the development of pancreatic fibrosis in alcoholics, the fibrosis types grouped according to Martin's classification were examined by immunohistochemistry using an antibody against alpha-smooth muscle actin (alpha-SMA). The initial stage of periacinar collagenization was also investigated by electron microscopy. The total incidence of pancreatic fibrosis at autopsy of the 29 alcoholics was significantly higher than that of the 40 non-alcoholics. Intralobular sclerosis was observed to be the most frequent type of fibrosis regardless of alcohol intake. No differences in the enhancement of alpha-SMA expression in each type of fibrosis were found between the alcoholics and non-alcoholics. Electron microscopically, myofibroblasts were found around acini in the early stage of periacinar collagenization, and were accompanied by numerous fine filaments (8-15 nm in diameter). The various changes in zymogen granules (ZG), lysosomes and lipid droplets were augmented in the acinar cells of alcoholics. Medium-density materials were also found in dilated rough endoplasmic reticulum (RER). The contents of ZG and RER occasionally leaked out. In conclusion, pancreatic fibrosis was increased in alcoholics; myofibroblasts may play an important role in the initial stage of periacinar collagenization; and the intracellular transport blockage of protein as represented by abnormalities of ZG, ER and lysosomes may contribute to the development of periacinar collagenization.     

Wheel/rail contact dynamics in turnout negotiations with combined nodal and non-conformal contact approach

In railroad turnouts, geometries of tongue and crossing rails are very complex and their shapes are changing along the track. Therefore, wheels are subjected to not only tread and flange contacts, but also the back-of-flange and top-of-flange contacts in the case of spring switches of tram vehicles. For this reason, one needs to deal with significant jumps in contact points for solving wheel/rail contact problems in turnout, and an accurate prediction of jumps in contact points is one of the most important issues that need to be carefully handled in the dynamic simulation of vehicle/turnout interactions. In this investigation, a numerical procedure that can be used for solving such a complex wheel/rail contact problem in turnout is proposed. In particular, a combined nodal and non-conformal contact approach is developed such that significant jumps in contact points are detected using the nodal search, while the exact location of contact point is then determined with continuous surface parameterizations using non-conformal contact equations. With this combined nodal and non-conformal contact approach for the contact geometry analysis of vehicle/turnout interactions, multiple look-up contact tables can be generated in an efficient way without losing accuracy. Since detailed contact search is performed off-line to obtain look-up contact tables, significant changes in contact points in turnout can be efficiently predicted on-line with tabular data to be interpolated in a standard way. Several numerical examples are presented in order to demonstrate the use of the numerical procedure developed in this investigation.     

Rheological properties and compatibility of NR/EPDM and NR/brominated EPDM blends

Ethylene–propylene–diene terpolymer (EPDM) was modified by bromination reaction. Blending the resulting brominated EPDM with natural rubber (STR5L) and blending the unmodified EPDM with STR5L at various compositions were carried out. The rheological properties of the blends were investigated using a capillary extrusion. Shear flow curves of the pure rubbers and their blends illustrated the pseudoplastic property as shear thinning behavior with a power law index n < 1. True shear viscosity of all blends showed the negative deviation in relation to their additive values. Rheological behavior and two T_g's found from the DSC thermograms at all blend compositions indicated blend incompatibility for both sets of blends. The incompatibility of the vulcanized blends was also found by measuring the spin–spin relaxation time T₂ by pulsed NMR. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 837–847, 2003     

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.