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.     

Electrical Breakdown Properties and Space Charge Formation in High Temperature Region in Ultraviolet Ray Irradiated PVC

Polyvinyl chloride (PVC) is the most popular insulating material for electric wiring instruments. However, an exothermic reaction above 150 °C may cause deterioration of the insulating properties of PVC. Therefore, it is important to clarify the heat degradation in PVC, not only to investigate the ignition of electrical wiring products but also to use electrical products safely. It is known that ultraviolet (UV) irradiation causes chemical deterioration of PVC and an increase in its conductivity. Generally, it has been thought that the electrical breakdown properties, electrical conduction, and insulating performance are affected by space charge accumulation in an insulating material. A high temperature pulsed electroacoustic (PEA) system usable up to 250 °C has been developed, and the PEA system can measure the space charge distribution and conduction current in the high temperature range simultaneously. In this investigation, the space charge distribution and conduction current were measured up to electrical breakdown in a non‐UV irradiated sample (normal PVC) and in 353 nm and 253 nm UV‐irradiated PVC samples in the range from room temperature to 200 °C in a DC electric field. In the short wavelength UV irradiated PVC sample (253 nm, 300 h), a deterioration of breakdown strength at 90 °C to 150 °C and negative packet‐like charges were observed at 60 °C and 100 °C, a positive charge accumulated in front of both the anode and cathode above 90 °C, and a higher electric field near the cathode side because the positive charge of the cathode side was greater.     

CD46 (membrane cofactor protein of complement, measles virus receptor): structural and functional divergence among species (review)

OBJECT: In this retrospective study, the authors analyzed the frequency, anatomical distribution, and appearance of traumatic brain lesions in 42 patients in a posttraumatic persistent vegetative state. METHODS: Cerebral magnetic resonance (MR) imaging was used to detect the number of lesions, which ranged from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases there was evidence on MR imaging of diffuse axonal injury, and injury to the corpus callosum was detected in all patients. The second most common area of diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem (74% of patients). In addition, 65% of these patients exhibited white matter injury in the corona radiata and the frontal and temporal lobes. Lesions to the basal ganglia or thalamus were seen in 52% and 40% of patients, respectively. Magnetic resonance imaging showed some evidence of cortical contusion in 48% of patients in this study; the frontal and temporal lobes were most frequently involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in this subgroup there was an 80% incidence of contralateral peduncular lesions in the midbrain. The most common pattern of injury (74% in this series) was the combination of focal lesions of the corpus callosum and the dorsolateral brainstem. In patients with no evidence of diffuse axonal injury in the upper brainstem (26% in this series), callosal lesions were most often associated with basal ganglia lesions. Lesions of the corona radiata and lobar white matter were equally distributed in patients with or without dorsolateral brainstem injury. Moreover, cortical contusions and thalamic, parahippocampal, and cerebral peduncular lesions were also similarly distributed in both groups. CONCLUSIONS: The data indicate that diffuse axonal injury may be the major form of primary brain damage in the posttraumatic persistent vegetative state. In addition, the authors demonstrated in this study that MR imaging, in conjunction with a precise clinical correlation, may provide useful supportive information for the accurate diagnosis of a persistent vegetative state after traumatic brain injury.     

Successful treatment by direct hemoperfusion of coma possibly resulting from mitochondrial dysfunction in acute valproate intoxication

PURPOSE: We evaluated the efficacy of direct hemoperfusion (DHP) for treatment of acute valproate (VPA) intoxication and speculate on the biochemical perturbations that suggest a mechanism of coma induced by VPA overdose. PATIENT AND METHODS: The comatose patient was hospitalized approximately 6 h after ingesting 18 g VPA. DHP, with 200 g activated charcoal, was performed for 6 h. The plasma concentrations of VPA and Glasgow coma scale scores after admission were estimated. Before and after DHP, urine samples were tested in serial fashion for VPA metabolites, organic acids, and acyl carnitine esters of fatty acids. RESULTS: Plasma VPA was efficiently adsorbed on activated charcoal. The patient's plasma concentration of VPA decreased from 471 microg/ml (2,830 microM) to 45 microg/ml (270 microM), at which point the patient became alert. The half-life (t1/2) of VPA was calculated as 4.4 h before DHP and as 1.8 h during DHP. Before DHP, lactate and VPA-glucuronide markedly increased in urine samples, but beta-keto-VPA, a major mitochondrial metabolite, was not detected. Urinary excretion of carnitine esters of medium chain (C8-C10) dicarboxylic acids was increased. After DHP, lactate and VPA-glucuronide decreased, but a significant amount of beta-keto-VPA was demonstrated. Carnitine esters of medium chain dicarboxylic acids were decreased. CONCLUSIONS: DHP with activated charcoal was effective treatment for the patient with acute VPA intoxication and coma. The onset of coma may have been related to inhibition of beta-oxidation in the mitochondria, which was reversible by elimination of plasma VPA by DHP.     

Efficiency of repeated batch penicillin fermentation using two fermentors. Computer simulation and optimisation

Repeated batch operation using two fermentors (RBTF) to penicillin fermentation was demonstrated by computer simulation to improve productivity. Three operation modes were compared: chemostat, repeated batch operation using a single fermentor (RBSF) and RBTF; in each case account was made of the lag period before growth. The simulated fermentor performances were assessed on the basis of the penicillin productivity and concentration; the simulation was based on published batch fermentation data. It was shown that RBTF was superior to RBSF and chemostat. The advantage of RBTF increased as the lag period became greater.     

Comparison of activities in selective catalytic reduction of NOx by C3H8 over Co/MFI, Fe/MFI, and H/MFI zeolite catalysts

The Co/MFI(SiO₂/Al₂O₃ = 30) were prepared by a precipitation method with NaOCl in alkali solutions exhibited high activities to N₂ at 250 °C for the selective catalytic reduction (SCR) of NO_x. These catalysts showed two UV–vis bands at 700 and 400 nm, indicating the presence of octahedral Co(III) as well as tetrahedral Co(II). The high SCR activity over such Co(III, II)/MFI(30) seems to come from Co(III)---O moieties. The Co(II)MFI(30) catalysts prepared from Co(II)Cl₂ exhibited low SCR activities due to the presence of tetrahedral Co(II) ions in MFI. Less CO formation occurred over Co/MFI catalysts. The Fe/MFI(30) catalyst exhibited high activity due to the presence of some Fe---O species in MFI but more amount of CO were produced during SCR. H/MFI(30) catalyst exhibited a good SCR activity. However, more amount of carbonaceous deposits were produced on it. The correlation between acid concentration and SCR activity was discussed over H/MFIs.     

Generation of gas bubbles in microflow using micropipette with ultrasound

Ultrasound was applied to a micropipette micromixer to improve dispersion of gas and liquid in a microchannel. Flow visualization using a high-speed camera was performed to examine the effect of ultrasonic irradiation on bubble generation in the microchannel. Basically, nitrogen gas was injected using a (0.5 µm ID) glass micropipette into ethanol flowing in a rectangular (100 µm×200 µm) microchannel on polydimethylsiloxane (PDMS). Gas and liquid flow rates were regulated using mass flow controllers. At aflow condition that is typical of bubbly flow, ultrasound was transmitted into the microchannel using a piezo-electric (PZT) transducer over a range of operating voltages (2 to 200 Vp-p) and frequencies (50 to 60 kHz). Images captured during the action of the PZT transducer indicate that bubble formation is influenced by ultrasound. When subjected to ultrasound above 50 Vp-p and at the resonant frequency of the PZT transducer, bubbles formed that were smaller and closer together, signifying enhanced shearing of the gas at the micropipette tip by the liquid. The observation of gas slugs occurring sooner might be attributed to the coalescence of gas bubbles that became closely spaced.     

Characteristics of thermally expanded core fiber

Thermally expanded core (TEC) fiber is expected to reduce fiber-to-fiber and fiber-to-laser diode connection loss. This paper describes the characteristics of TEC fiber theoretically and experimentally. We reveal theoretically that when fabricating TEC fiber the mode field diameter (MFD) is enlarged more effectively by increasing the heating temperature rather than the heating time. In the 1300-1600°C temperature range with heating times between 0 and 60 min, it is necessary to control the temperature accurately so that no deviation from the target temperature is more than ±30°C. This is in order to ensure that any connection loss caused by MFD mismatch is less than 0.1 dB. We show experimentally that the propagation loss of TEC fiber is dependent on the heating region and wavelength by using a micro burner with a propane/oxygen flame. Based on the relationship between the loss characteristics and the expanded MFD, we suggest a method for nondestructively measuring the MFD in TEC fibers     

Respiratory mechanics during mechanical ventilation: a model study on the effects of leak around a tracheal tube

Recently published studies indicate a potential clinical application of PET in head and neck tumors. In the preoperative staging phase, PET enables confirmation of regional lymph node extension and guides nodal neck dissection or systemic treatment. In this phase, a high negative predictive value, near 100%, could make it possible to avoid many negative neck dissections. This is a reliable technique for confirming or excluding the presence of recurrent/residual tumor and for obtaining an early evaluation of chemotherapeutic and radiotherapeutic response. PET imaging in many cases makes it possible to locate and guide histological study of tumors with an unknown primary. PET imaging for these indications is a perfect complementary method for clinical exploration and better than other imaging techniques.     

Novel hepatitis C virus protease inhibitors: thiazolidine derivatives

This study evaluated the inhibitory effects of thiazolidine derivatives on hepatitis C virus (HCV) protease and other human serine proteases. The inhibition efficacy was tested with a reversed-phase high-performance liquid chromatography (HPLC) assay system using a NS3-NS4A fusion protein as the HCV protease and a synthetic peptide substrate that mimics the NS5A-5B junction. Nine thiazolidine derivatives showed more than 50% inhibition at 50 microg/ml. The most potent derivative was RD4-6250, with 50% inhibition at a concentration of 2.3 microg/ml; this concentration was lower than those of other protease inhibitors reported previously. The most selective derivative was RD4-6205, with 50% inhibition at a concentration of 6.4 microg/ml, a lower concentration than those on other serine proteases (chymotrypsin, trypsin, plasmin, and elastase). These results suggest that the RD4-6205 skeleton is an important structure for inhibitory activity on the HCV protease NS3-NS4A.