Search

Background Studies on renal solute carrier transporters have made the renal pathophysiology be in progress towards more mechanistic and the knowledge on renal drugs including drug-drug interaction be more evidentiary. Among the evidence, uricosuric phenomenon has been known that rodent experimental model is also useful for predicting human uricosuria. Objectives The aim of this study was to assess the substrate uptake at the overexpression of renal transporters, OAT1, OAT3 and URAT1 at kidney proximal tubular cell lines with or without a commercial herbal medicine, Keishibukuryogan (K-06) and to further measure serum and urinary uric acid concentrations in the setting of potassium oxonate (PO)-induced ICR mouse model with or without K-06. Methods The transporter-expressed HEK293-OAT1 and HEK293-OAT3 cells were seeded on BD poly-d-lysine microplates to uptake the [3H] estrone sulfate for 5 min in absence or presence of K-06. URAT1 was overexpressed using Xenopus oocytes being injected with in vitro-copied RNA of URAT1, and then to measure the uptake of [14C] uric acid with/without K-06. Total radioactivity was measured using a liquid scintillation counter. Serum and urinary uric acid was measured in PO ICR mice after three-day intake of K-06. They were assigned by 4 per each group; 1) control group, 2) PO-induced group, 3) PO-induced with allopurinol 50 mg/kg/day intake group and 4) PO-induced with allopurinol plus K-06 300 mg/kg/day intake group. Results To determine the kinetic parameters of concentration-dependent uptake of overexpressed OAT1 and OAT3 transporters in HEK293 cells, the K-06 inhibitory parameters on OAT1 and OAT3 were presented with the IC50 values of 49.3 and 31.5 µg/mL, respectively. The K-06 inhibited URAT1 with IC50 of 59.3 µg/mL. The K-06 (300 mg/kg) reduced serum levels of uric acid approximately 30% compared to that of PO-control group (p=0.039) and K-06 showed the slight elevation of urinary uric acid by 12% compared to that of PO-control group with no statistical significance. Conclusions The present findings demonstrated that the K-06 modulated basolateral and apical renal transporters and the K-06 showed the slight increased uric acid excretion and the uric acid lowering effect in experimental mouse setting. References [1] Becker GJ, Hewitson TD. Animal models of chronic kidney disease: useful but not perfect. Nephrol Dial Transplant2013;28:2432–8. doi: 10.1093/ndt/gft071 [2] Key difference between mouse and human kidney cells. Which isavailable at https://www.sciencedaily.com/releases/2016/03/160318181600.htm Acknowledgements This study was supported by the Traditional Korean Medicine R and D program funded by the Ministry of Health and Welfare through the Korea Health Industry Development Institute (KHIDI, Grant # HI16C0864). The commercial herbal products, Keishibukuryogan (K-06) were donated by the virtue of Kracie Pharma, Co., Ltd. Disclosure of Interest None declared

BACKGROUND Criteria for screening preterm infants for retinopathy of prematurity vary around the world. We aimed to analyse the efficacy of alternative screening criteria. DESIGN We collected retrospective data at a tertiary level neonatal nursery. PARTICIPANTS Our participants were 1007 babies, born between 1997 and 2011, at

Background Uric acid homeostasis is a set of the balance in glomerular filtration, tubular secretion, reabsorption, and excretion. In the course of cascade, two kinds play a pivotal role; efflux transporters in apical at renal proximal tubular membrane, uptake ones in basolateral at membrane. The former has been of interest in the targets for uricosuric effects, however, dual modulation of the two could keep uric acid balance in stable ways. Objectives The aim of this study was to assess the uptake of seven test articles in the course of the expressions of apical/basolateral transporters in potassium oxonate (PO)-treated kidney epithelial cell lines (Caco-2, MDCK, LLC-PK1) and ICR mice. Methods The selected cell lines were treated with potassium oxonate (0.25 mM) and then modulated by seven test articles, the commercial herbal products (SITK01 through SITK06 and SITT01) at dose range of 0.015–1 mg/mL. To determine efficacious dose range by each test article, three cell lines, Caco-2, MDCK and LLC-PK1 cells were assessed with MTT assay. Forty eight ICR mice were injected intraperitoneally with PO at a dose of 200 and 400 mg/kg and then blood draws were conducted 0, 6, 12, 24, 72 hours after PO administration. The levels of uric acid and transporters were also measured by ELISA assay and Western blotting analysis in those cell lines. Results Treatment of SITK01 through SITK03 and SITT01 at concentration (250 mg/mL) decreased the cell viability. The PO-stimulated kidney epithelial cells with SITK01 through SITK03 treatment increased GLUT9 by 2.5 folds and decreased OAT3 by 1.5 folds (versus controls, p=0.012, and p=0.017, respectively). In PO-treated mice, uric acid levels were increased through GLUT9 and OAT3 transporters. The results indicated that SITK01, SITK02, and SITK03 showed the potential on uricosuric effects in a dual modulation of apical/basolateral sides of kidney epithelial tubular membranes. Conclusions The present findings demonstrated that three commercial herbal products showed potentials to reduce hyperuricaemia-induced condition by changing protein expression levels in a transporter-uptake assay. The OAT3 and GLUT9 could be further investigated as the uricosuric group-targets on the bilateral sides at kidney epithelial tubular membranes. References Fromm MF, Konig J. Transporters and drug-drug interactions: important determinants of drug disposition and effects. 2015 Nature Reviews Drug Discovery 14, 543–560. Giacomini KM, Lawrence Lin, Sook Wah Yee, Richard B. Kim & Kathleen. SLC transporters as therapeutic targets: emerging opportunities. 2015 Nature Reviews Drug Discovery 14, 543–560. Acknowledgements This study was supported by the Traditional Korean Medicine R&D program funded by the Ministry of Health & Welfare through the Korea Health Industry Development Institute (KHIDI, Grant # HI16C0864). The commercial products were donated by the virtue of Kracie Pharma, Ltd. and Tsumura & Co. Disclosure of Interest None declared

Background Our previous study showed synergistic responses in TNF-alpha (TNF-α) and interleukin-6 with the combination of methotrexate (MTX) and aconite. Modulation of those cytokines has not been applied to rheumatoid arthritis (RA)-mimicked in vivo models. Objectives To translate in vitro effects of MTX, aconite, and MTX/aconite combination towards anti-arthritic responses in vivo, we investigated arthritis index (AI), histopathologic changes, and levels of TNF-α, immunoglobulin G (IgG) 2a and 2b in a collagen-induced arthritis (CIA) setting. Methods CIA was induced in five male DBA/OlaHsd mouse per group by intradermal injection of bovine collagen type II and Complete Freund9s Adjuvant. In Day21, a bovine collagen type II and Incomplete Freund9s Adjuvant were given for booster infection. The mice of arthritis onset were treated daily throughout Day49 with per oral administration of pre-investigated ratios of three to one; MTX (3 mg/kg), aconite (Aconibal®, 1 mg/kg), and MTX/aconite (3 and 1 mg/kg) combination. The AIs were evaluated every week. Histological changes, levels of TNF-α as well as IgG2a and IgG2b in blood using ELISA kit were evaluated at finals. Repeat measure and one-way ANOVA were analysed using SPSS (ver. 18.0 KO for Windows; SPSS Inc., Chicago, IL, USA) to evaluate inter-period and inter-group differences with Tukey9s post-hoc tests. Results The CIA phenotypes adequately presented through three groups9 AI reductions (CIA vs. MTX, aconite, or MTX/aconite; p Conclusions Synergistic in vitro effects of MTX and aconite combination brought the partial in vivo phenotypic responses: Aconite showed more AI changes than MTX did in 4, 5, and 6 weeks. However, we found the presence of partial FcγRIIB affinity of binding modulation that MTX/aconite could enhance preventing monocyte/macrophage activation via immune complex in RA pathogenesis, as was other benefits of the combination except direct synergies. References Oh DS, Park G, Choi S. Characterising multiple molecule-modulating response of TNF-alpha and interleukin-6 by combination of methotrexate and aconite in interferon gamma-induced toxicity setting. Ann Rheum Dis 2016;75:Suppl2 909–910. Wijngaarden S, van Roon JA, van de Winkel JG, Bijlsma JW, Lafeber FP. Down-regulation of activating Fcgamma receptors on monocytes of patients with rheumatoid arthritis upon methotrexate treatment. Rheumatology (Oxford) 2005;44:729–734. Stewart R, Hammond SA, Oberst M, Wilkinson RW. Down-regulation of activating Fcgamma receptors on monocytes of patients with rheumatoid arthritis upon methotrexate treatment. J Immunother Cancer 2014;2:29. Acknowledgements This study was supported by KIOM (Grant # K17252). The commercial product was donated by the virtue of HanPoong Pharmaceutical Company. Disclosure of Interest None declared

Tungsten inert gas (TIG) welding is most frequently used for arc study because it is clean and easy to control welding factor. Many researchers have been focused on the plasma stream to find out the relationship between vertex angle and penetration of the tungsten electrode in TIG welding. Moreover, researchers studied the characteristics of vertex angle and arc pressure and heat flux distribution of the tungsten electrode. In addition, they have carried out factors that have influence on the behaviour of the molten pool. Previous studies assumed that arc pressure was dominant for the force that physically works on the surface of the molten pool, neglecting the shield gas pressure. In addition, they have been focused on the protection of molten weld pool from exposure to the atmosphere. The object of this study is to investigate the effect of shield gas pressure on the surface of the molten pool by measuring the distribution of arc pressure and shield gas pressure compared with arc physical result...

This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m(-2) plus doxorubicin 60 mg m(-2) (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m(-2) plus cisplatin 70 mg m(-2) (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted withor=73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy.

Arc pressure is an important factor in understanding physical arc phenomena, especially its effects on the penetration, size and shape of GTA welding. The purpose of the present study is to derive the current density distribution on the anode base metal from the measured arc pressure distribution in GTA welding using the results from previous investigators. Using the measured arc pressure distribution on the anode base metal in GTA welding from the central part to the circumference and the equations of Lin et al. and Maecker, the current density distribution was derived. Applying the derived equation from the present work, the current density distribution was calculated from the low current region to the high current region by means of shield gas mixing ratio. It is compared and discussed with the practical welding current and the derived current by numerical integration of the current density distribution from the central part to the circumference region.

Criteria for screening preterm infants for retinopathy of prematurity vary around the world. We aimed to analyse the efficacy of alternative screening criteria.We collected retrospective data at a tertiary level neonatal nursery.Our participants were 1007 babies, born between 1997 and 2011, at32 weeks gestational age or1500 g birth weight (as recommended by the National Health and Medical Research Council in 1996), who had completed follow-up to full retinal vascularization, with defined presence or absence of retinopathy of prematurity.We determined whether disease would be detected using an alternative Australian screening model (gestational age30 weeks or birth weight1250 g) or screening criteria utilized in developed countries with similar standards of neonatal care.Detection of retinopathy of prematurity is our main outcome.Using several of the alternative criteria, two neonates with clinically significant retinopathy of prematurity, one of whom required laser treatment to preserve sight, would not have been screened, and their disease may have gone undetected. Use of30 weeks gestational age or1500 g birth weight as the criteria would still have screened these infants but would have reduced the number of infants screened by 24.9%.Some commonly utilized international screening criteria for retinopathy of prematurity may risk clinically significant cases being missed and others may screen babies unnecessarily. Alternative criteria should be considered and '30 weeks gestational age and/or1500 g birth weight' appears a viable option.

Highly porous hydroxyapatite (HA) scaffolds were developed as bone graft substitutes using a template coating process, characterized, and seeded with bone marrow-derived mesenchymal stem cells (BMSCs). To test the hypothesis that cell-seeded HA scaffolds improve bone regeneration, HA scaffolds without cell seeding (HA-empty), HA scaffolds with 1.5 × 10(4) BMSCs (HA-low), and HA scaffolds with 1.5 × 10(6) BMSCs (HA-high) were implanted in a 10-mm rabbit radius segmental defect model for 4 and 8 weeks. Three different fluorochromes were administered at 2, 4, and 6 weeks after implantation to identify differences in temporal bone growth patterns. It was observed from fluorescence histomorphometry analyses that an increased rate of bone infiltration occurred from 0 to 2 weeks (p0.05) of implantation for the HA-high group (2.9 ± 0.5 mm) as compared with HA-empty (1.8 ± 0.8 mm) and HA-low (1.3 ± 0.2 mm) groups. No significant differences in bone formation within the scaffold or callus formation was observed between all groups after 4 weeks, with a significant increase in bone regenerated for all groups from 4 to 8 weeks (28.4% across groups). Although there was no difference in bone formation within scaffolds, callus formation was significantly higher in HA-empty scaffolds (100.9 ± 14.1 mm(3) ) when compared with HA-low (57.8 ± 7.3 mm(3) ; p ≤ 0.003) and HA-high (69.2 ± 10.4 mm(3) ; p ≤ 0.02) after 8 weeks. These data highlight the need for a better understanding of the parameters critical to the success of cell-seeded HA scaffolds for bone regeneration.

The etiology and significance of cardia intestinal metaplasia (CIM) is disputed. CIM may represent a form of Barrett's esophagus due to reflux or could reflect generalized gastric intestinal metaplasia due to Helicobacter pylori. The aim of this study was to utilize gene expression data to compare CIM to Barrett's and gastric intestinal metaplasia. Endoscopic biopsies were classified by endoscopic and histologic criteria as CIM (n= 33), Barrett's (n= 25), or gastric intestinal metaplasia of the antrum or body (n= 18). The squamocolumnar and gastroesophageal junctions were aligned in CIM patients and patients with diffuse gastric intestinal metaplasia were excluded. H. pylori was tested for in the biopsies of all patients. After laser-capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of a panel of nine genes that has been shown to differentiate Barrett's from other foregut mucosa. Cluster analysis with linear discriminant analysis of the expression data was used to classify each sample into groups based solely on similarity of gene expression. Cluster analysis was performed for three groups (CIM vs. Barrett's vs. gastric intestinal metaplasia) and two groups (CIM + Barrett's vs. gastric intestinal metaplasia). There was no difference in H. pylori infection among groups (P= 0.66). Clustering into three groups resulted in frequent misclassification between CIM and Barrett's while misclassification of gastric intestinal metaplasia was uncommon. The CIM and Barrett's groups were then combined for two group clustering and linear discriminant analysis correctly predicted 95% of CIM and Barrett's samples and 83% of gastric intestinal metaplasia samples based on gene expression alone. In conclusion, the gene expression profiles of CIM and Barrett's esophagus were similar in 95% of biopsies and differed significantly from that of gastric intestinal metaplasia. The indistinguishable gene expression profile of CIM and BE suggests that they may share a common etiology in the majority of patients with a similar biology, and calls into question the perception that CIM is an innocuous process.

The Korea Atomic Energy Research Institute (KAERI) has been developing a dual-cooled annular fuel for the power uprate of 20% in an optimized pressurized water reactor (PWR) in Korea, OPR1000. The dual-cooled annular fuel is configured to allow the coolant flow through the inner channel as well as the outer channel. Several thermal-hydraulic issues exist for the application of the dual-cooled annular fuel to OPR1000. One of the key issues is the hypothetical event of inner channel blockage because the inner channel is an isolated flow channel without the coolant mixing between the neighboring flow channels. The inner channel blockage could cause the Departure from Nucleate Boiling (DNB) in the inner channel that eventually results in a fuel failure. A long lower end cap for the annular fuel was invented to provide flow holes by perforating the side surface of the end cap body. The side holes in the lower end cap are expected to supply a minimum coolant in the inner channel in order to prevent the DNB occurrence in the event of partial or even complete blockage of the inner channel entrance. But due to very unusual shape of the lower end cap, it is difficult to estimate the flow resistance of the side flow holes using empirical equations available in the open literatures. Experimental and computational fluid dynamics (CFD) study were performed to investigate the bypass flow through the side holes of the end cap in the case of complete entrance blockage of the inner channel. The form loss coefficient in the side holes was also estimated by using the pressure drop along the bypass flow path.Copyright © 2011 by KSME

In this paper, we introduce the wind-photovoltaic hybrid power system (WPHPS) installed in Mongolia and the safety assessment for the WPHPS, which was implemented to prevent the failure mode. In order to prevent desertification and build afforestation, two groups of photovoltaic systems were installed in the Gobi desert. One of the generators, which produces 70kW of the power, operates as the power plant for cultivation in this area and another one works with wind power generator. To operate these installed systems effectively, must be implemented the safety assessment. Failure Mode and Effect Analysis (FMEA) was used as a safety assessment method in this study. The 28 of important assemblies of WPHPS were evaluated by FMEA and the results carried out 47 failure modes.

We report the hydrogen sensing properties of a sensor using TiO 2 nanotube arrays. The TiO 2 nanotube arrays were fabricated by anodization on titanium foil, in an electrolyte containing 0.5 wt% hydrofluoric acid mixed with water, the electric potential being 15V. TiO 2 nanotube arrays were annealed at 600 Celsius for 1 h. The sensors were equipped with platinum electrodes. These two were connected with a metal wire using silver paste. The measurements of the sensor's electrical resistance were performed in NTP. The hydrogen sensor using TiO 2 nanotube arrays shows a linear sensitivity with various hydrogen concentrations. After repeating exposure to hydrogen at room temperature, the sensor's resistance indicated a stable recovery to its initial resistance. The reproducibility of this exam is reliable.

The risk of deep vein thrombosis (DVT) in the peri-operative period is significant, but can be reduced with the use of mechanical intermittent pneumatic compression (IPC). These devices have reached widespread use in hospitals and have been found to be effective prophylactic measures against DVT. This study evaluates the latest design features of one particular IPC device in comparison to current models.Duplex ultrasound scanning was performed on 40 lower extremities of 20 healthy volunteers before and during the application of the IPC device (VenaFlow System, Aircas, NJ, USA. Two hemodynamic parameters were measured, acceleration time from spontaneous baseline venous flow and peak vein velocity. All measurements were obtained by scanning proximal to the saphenofemoral junction in the common femoral vein in both extremities for each subject. Data were obtained from 3 compression cycles and averaged for each extremity. Results were compared with a recent prospective study form our center using a slow-filling and a rapid-filling sequential IPC devices.The medians for spontaneous average peak velocities at rest of the right and left lower extremities were 26 cm/s and 24.1 cm/s. The median augmented peak velocities during the compression cycle of the device in the right and left side were 79.6 cm/s and 79.0 cm/s. This represented a 306.2% increase in average peak velocity on the right side and a 327.8% increase on the left side. The median acceleration time was 305 ms +/- 40 in the left and 310 ms +/- 50 in the right limb. There was no statistically significant difference in the spontaneous and augmented velocities between the right and left lower extremities in each subject. In comparison to existing slow- and rapid-filling IPC devices the VenaFlow System had superior peak velocities and shorter acceleration times.The use of elliptical, sequential and rapid-filling compression of the leg with overlapping air-cells produces significant hemodynamic changes in the common femoral vein, which are superior to other sequential slow- or rapid-filling IPC devices. Randomized studies should be performed to determine the efficacy of this new device in DVT prevention.

Corneal endothelial cells are differentiated cells and are thus incapable of physiologic regeneration. In a search for a growth factor that would promote optimal proliferation of corneal endothelial cells in the absence of other modulating activities, the effect of insulin-like growth factor-I (IGF-I) on rabbit corneal endothelial cells was studied. In addition, cellular effector molecules responsible for the signal pathway for IGF-I were studied. IGF-I at 50 ng/ml stimulated corneal endothelial cell proliferation after at least 8 h of treatment. IGF-I did not change cell shape of corneal endothelial cells: the cells treated with IGF-I at 50 ng/ml maintained polygonal morphology regardless of the duration of exposure. IGF-I did not alter collagen phenotypes either qualitatively or quantitatively: the treated cells continued to synthesize types IV and VIII collagen, as did the control cells. The steady-state levels of alpha 2(I) collagen RNA and alpha 2(IV) RNA were not altered by IGF-I treatment. Immunohistochemical analysis showed that IGF-I is present in corneal endothelium in vivo, while the underlying Descemet's membrane demonstrated no staining. Corneal endothelial cells also produce IGF binding protein-2 (IGFBP-2), which appears to bind IGF-I that has been introduced exogenously in the medium. Further investigation as to how the signals of IGF-I were transmitted for the biological activities demonstrated that the expression of insulin receptor substrate-1 (IRS-1) is up-regulated by IGF-I treatment, while PLC-gamma 1 expression is not altered by this growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: despite numerous reports on the distribution of reflux in patients with venous ulceration, there is no consensus on the contribution of each venous system. This study was performed to evaluate the distribution of reflux in this group of patients. Methods: a literature search from 1980 to 1998 was performed. Because duplex scanning is the best method for detecting venous reflux, we only included reports that used this diagnostic modality. All studies with less than 30 ulcerated limbs were excluded. Since most reports did not give detailed data on perforator veins, reflux in these veins was combined with the superficial and deep veins. Documented episodes of superficial or deep vein thrombosis were noted.Results: thirteen studies that included 1249 ulcerated limbs fulfilled the inclusion criteria. The mean age of patients was 59 years (95% CI: 54–63, range: 14–93). Reflux was detected in 1153 (92%) of limbs. Reflux confined to the superficial veins alone was seen in 45% of limbs, in the deep veins alone in 12% and in both the superficial and deep veins in 43% of limbs. The overall involvement of the superficial veins was 88% and of the deep veins 56% (p