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.     

Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.     

Right atrial contractile performance in patients with myocardial infarction

To evaluate right atrial (RA) contractile performance in patients with myocardial infarction, we validated a cineangiographic method of RA volume measurement, and investigated RA volume change in 'normal' individuals and patients with a previous myocardial infarction. Sixteen silicone rubber RA casts made from human cadavers were filmed in the postero-anterior and left lateral projections. The cast volumes calculated following Simpson's rule were in good agreement with those measured by water replacement (r = 0.992, P < 0.01). At cardiac catheterization, biplane RA cineangiography was performed in 19 'normal' individuals (N group), in 14 patients with a previous antero-septal infarction (AMI group) and in seven patients with a previous inferior infarction (IMI group). The RA volume-time curve was constructed at 20-40 ms intervals for one cardiac cycle. RA volume at the beginning of the atrial contraction (RAVd), which was defined as the 'preload' of the RA, tended to be larger in both the AMI and IMI groups compared with 'normal' individuals. The RA ejection volume was significantly larger in both the AMI (18.4 +/- 2.1 ml.m-2, P < 0.01) and IMI groups (19.4 +/- 2.8, P < 0.01) than in the N group (14.5 +/- 1.9), even for a comparable level of RAVd (range from 26 to 36 ml.m-2) (18.6 +/- 2.1, P < 0.01, 18.2 +/- 2.0, P < 0.01, 14.7 +/- 1.9, respectively). These results suggest that RA contraction increases in patients with myocardial infarction by increasing both the 'preload' and 'contractility' of the RA.     

Consequences of structural disorder on laser properties in quantumwire lasers

The effect of interface-roughness-related disorder on the electronic and optoelectronic properties of a quantum wire structure are studied. It is seen that the disorder causes strong localization in the quasi-one-dimensional system. While the electronic states are seriously perturbed, the density of states is not affected drastically. Optoelectronic properties as reflected in the interband transition related phenomenon are not found to suffer significant deterioration as a result of the disorder. However, the results suggest that intraband relaxation processes may be seriously affected because of electron (hole) states being localized in different regions of the wire     

Fuzzy rule-based signal processing and its application to imagerestoration

A novel signal processing technique based on fuzzy rules is proposed for estimating nonstationary signals, such as image signals, contaminated with additive random noises. In this filter, fuzzy rules concerning the relationship between signal characteristics and filter design are utilized to set the filter parameters, taking the local characteristics of the signal into consideration. The fuzzy rules are found to be quite effective, since the rules to set the filter parameters are usually expressed in an ambiguous style. The high performance of this filter is demonstrated in noise reduction of a 1-D test signal and a natural image with various training signals     

Lipid-Lowering Effect of Eriocitrin, the Main Flavonoid in Lemon Fruit, in Rats on a High-Fat and High-Cholesterol Diet

ABSTRACT:  Eriocitrin (eriodictyol 7- O -β-rutinoside) is the main flavonoid in lemon fruit. In this study, eriocitrin was investigated for its lowering effect on serum and hepatic lipids in high-fat and high-cholesterol fed rats. Rats in the control group ( N = 6) were fed a 20% lard and 1% cholesterol diet for 21 d, and rats in the 0.35% eriocitrin group ( N = 6) and 0.70% eriocitrin group ( N = 6) were fed a diet supplemented with eriocitrin 0.35% and 0.70%, respectively. The content of hepatic total cholesterol and triglyceride in the eriocitrin group was no different from that of the control group. The total cholesterol, VLDL+LDL, triglyceride, and phospholipid in the serum of the 0.35% eriocitrin group showed significantly lower concentrations than the control group ( P < 0.05), although there was no difference in the HDL concentrations among the groups. The lowering effect of eriocitrin for serum total cholesterol was thought to be caused by a decrease in VLDL+LDL. The 0.35% eriocitrin group was shown to have a significant increase in excretion of fecal bile acid ( P < 0.05) and a tendency for enhanced hepatic m-RNA levels of LDL receptor in comparison with the control group.     

Virtual Fiber Configuration for Dynamic Lightpath Establishment in Large-scaled Optical Networks

Recently, progress has been made in the Generalized Multi-Protocol Label Switching (GMPLS) and Automatic Switched Optical Networks (ASON) standardizations. These technologies realize construction of large-scaled optical networks, interconnections among single-domain Wavelength Division Multiplexing (WDM) networks, and direct communication over multi-domain WDM networks. Meanwhile, it is known that the topology of the Internet exhibits the power-law attribute. Since the topology of the Internet, which is constructed by interconnecting ASs, exhibits the power-law, there is a possibility that large-scale WDM networks, which are constructed by interconnecting WDM networks, will also exhibit the power-law attribute. One of the structural properties of a topology that adheres to the power-law is that most nodes have just a few links, although some have a tremendous number of them. Another property is that the average distance between nodes is smaller than in a mesh-like network. A natural question is how such a structural property performs in WDM networks. In this paper, we first investigate the property of the power-law attribute of physical topologies for WDM networks. We compare the performance of WDM networks with mesh-like and power-law topologies, and show that links connected to high-degree nodes are bottlenecks in power-law topologies. To relax this, we introduce a concept of virtual fiber, which consists of two or more fibers, and propose its configuration method to utilize wavelength resources more effectively. We compare performances of power-law networks with and without our method by computer simulations. The results show that our method reduces the blocking probabilities by more than one order of magnitude.     

The Gmicro/500 superscalar microprocessor with branch buffers

The Gmicro/500, which features a RISC-like dual-pipeline structure for high-speed execution of basic instructions and represents a significant advance for the TRON architecture, is presented. Upwardly-object-compatible with earlier members of the Gmicro series, this microprocessor uses resident dedicated branch buffers to greatly enhance branch instruction execution speed. Its microprograms simultaneously use dual execution blocks to execute high-level language instructions effectively. Fabricated with a 0.6-μm CMOS technology on a 10.9-mm×16-mm die, the chip operates at 50/66 MHz and achieves a processing rate of 100/132 MIPS