A direct reflection OLVF debris detector based on dark-field imaging

Science.gov (United States)

Li, Bo; Xi, Yinhu; Feng, Song; Mao, Junhong; Xie, You-Bai

2018-06-01

To solve the problems of monitoring wear debris in black oil, a direct reflection online visual ferrograph (OLVF) debris detector is presented. In current OLVF detectors, a reflected light source is used. The emitted light is reflected by wear debris directly instead of passing through the lube oil. Therefore, the transparency of the lube oil ceases to matter. Two experiments were conducted to validate the wear debris imaging feasibility and effectiveness of the newly developed detector. The results show that the visual feature information of the wear debris can be reliably obtained from black oil by this detector, and it can also be used to track the fast-changing wear of tribopairs at different wear stages. To the best of our knowledge, to date there is no other report for solving this issue.

Microscopical analysis of synovial fluid wear debris from failing CoCr hip prostheses

Science.gov (United States)

Ward, M. B.; Brown, A. P.; Cox, A.; Curry, A.; Denton, J.

2010-07-01

Metal on metal hip joint prostheses are now commonly implanted in patients with hip problems. Although hip replacements largely go ahead problem free, some complications can arise such as infection immediately after surgery and aseptic necrosis caused by vascular complications due to surgery. A recent observation that has been made at Manchester is that some Cobalt Chromium (CoCr) implants are causing chronic pain, with the source being as yet unidentified. This form of replacement failure is independent of surgeon or hospital and so some underlying body/implant interface process is thought to be the problem. When the synovial fluid from a failed joint is examined particles of metal (wear debris) can be found. Transmission Electron Microscopy (TEM) has been used to look at fixed and sectioned samples of the synovial fluid and this has identified fine (< 100 nm) metal and metal oxide particles within the fluid. TEM EDX and Electron Energy Loss Spectroscopy (EELS) have been employed to examine the composition of the particles, showing them to be chromium rich. This gives rise to concern that the failure mechanism may be associated with the debris.

Applicability of out-of-pile fretting wear tests to in-reactor fretting wear-induced failure time prediction

Science.gov (United States)

Kim, Kyu-Tae

2013-02-01

In order to investigate whether or not the grid-to-rod fretting wear-induced fuel failure will occur for newly developed spacer grid spring designs for the fuel lifetime, out-of-pile fretting wear tests with one or two fuel assemblies are to be performed. In this study, the out-of-pile fretting wear tests were performed in order to compare the potential for wear-induced fuel failure in two newly-developed, Korean PWR spacer grid designs. Lasting 20 days, the tests simulated maximum grid-to-rod gap conditions and the worst flow induced vibration effects that might take place over the fuel life time. The fuel rod perforation times calculated from the out-of-pile tests are greater than 1933 days for 2 μm oxidized fuel rods with a 100 μm grid-to-rod gap, whereas those estimated from in-reactor fretting wear failure database may be about in the range of between 60 and 100 days. This large discrepancy in fuel rod perforation may occur due to irradiation-induced cladding oxide microstructure changes on the one hand and a temperature gradient-induced hydrogen content profile across the cladding metal region on the other hand, which may accelerate brittleness in the grid-contacting cladding oxide and metal regions during the reactor operation. A three-phase grid-to-rod fretting wear model is proposed to simulate in-reactor fretting wear progress into the cladding, considering the microstructure changes of the cladding oxide and the hydrogen content profile across the cladding metal region combined with the temperature gradient. The out-of-pile tests cannot be directly applicable to the prediction of in-reactor fretting wear-induced cladding perforations but they can be used only for evaluating a relative wear resistance of one grid design against the other grid design.

Debris flow-induced topographic changes: effects of recurrent debris flow initiation.

Science.gov (United States)

Chen, Chien-Yuan; Wang, Qun

2017-08-12

Chushui Creek in Shengmu Village, Nantou County, Taiwan, was analyzed for recurrent debris flow using numerical modeling and geographic information system (GIS) spatial analysis. The two-dimensional water flood and mudflow simulation program FLO-2D were used to simulate debris flow induced by rainfall during typhoon Herb in 1996 and Mindulle in 2004. Changes in topographic characteristics after the debris flows were simulated for the initiation of hydrological characteristics, magnitude, and affected area. Changes in topographic characteristics included those in elevation, slope, aspect, stream power index (SPI), topographic wetness index (TWI), and hypsometric curve integral (HI), all of which were analyzed using GIS spatial analysis. The results show that the SPI and peak discharge in the basin increased after a recurrence of debris flow. The TWI was higher in 2003 than in 2004 and indicated higher potential of landslide initiation when the slope of the basin was steeper. The HI revealed that the basin was in its mature stage and was shifting toward the old stage. Numerical simulation demonstrated that the parameters' mean depth, maximum depth, affected area, mean flow rate, maximum flow rate, and peak flow discharge were increased after recurrent debris flow, and peak discharge occurred quickly.

Wear behaviors of pure aluminum and extruded aluminum alloy (AA2024-T4) under variable vertical loads and linear speeds

Science.gov (United States)

Jung, Jeki; Oak, Jeong-Jung; Kim, Yong-Hwan; Cho, Yi Je; Park, Yong Ho

2017-11-01

The aim of this study was to investigate the transition of wear behavior for pure aluminum and extruded aluminum alloy 2024-T4 (AA2024-T4). The wear test was carried using a ball-on-disc wear testing machine at various vertical loads and linear speeds. The transition of wear behaviors was analyzed based on the microstructure, wear tracks, wear cross-section, and wear debris. The critical wear rates for each material are occurred at lower linear speed for each vertical load. The transition of wear behavior was observed in which abrasion wears with the generation of an oxide layer, fracture of oxide layer, adhesion wear, severe adhesion wear, and the generation of seizure occurred in sequence. In case of the pure aluminum, the change of wear debris occurred in the order of blocky, flake, and needle-like debris. Cutting chip, flake-like, and coarse flake-like debris was occurred in sequence for the extruded AA2024-T4. The transition in the wear behavior of extruded AA2024-T4 occurred slower than in pure aluminum.

Determination of a Wear Initiation Cycle by using a Contact Resistance Measurement in Nuclear Fuel Fretting

International Nuclear Information System (INIS)

Lee, Young Ho; Kim, Hyung Kyu

2008-01-01

In nuclear fuel fretting, the improving of the contact condition with a modified spring shape is a useful method for increasing the wear resistance of the nuclear fuel rod. This is because the fretting wear resistance between the fuel rod and grid spring is mainly affected by the grid spring shape rather than the environment, the contact modes, etc. In addition, the wear resistance is affected by the wear debris behavior between contact surfaces. So, it is expected that the wear initiation of each spring shape should be determined in order to evaluate a wear resistance. However, it is almost impossible to measure the wear behavior in contact surfaces on a real time basis because the contact surfaces are always hidden. Besides, the results of the worn surface observation after the fretting wear tests are restricted to archive the information on the wear debris behavior and the formation mechanism of the wear scar. In order to evaluate the wear behavior during the fretting wear tests, it is proposed that the contact resistance measurement is a useful method for examining the wear initiation cycle and modes. Generally, fretting wear damages are rapidly progressed by a localized plastic deformation between the contact surfaces, crack initiation and fracture of the deformed surface with a strain hardening difference between a surface and a subsurface and finally a detachment of wear debris. After this, wear debris is easily oxidized by frictional heat, test environment, etc. At this time, a small amount of electric current applied between the contact surfaces will be influenced by the wear debris, which could be an obstacle to an electric current flow. So, it is possible to archive the information on the wear behavior by measuring the contact resistance. In order to determine the wear initiation cycle during the fretting wear tests, in this study, fretting wear tests have been performed by applying a constant electric current in room temperature air

Dynamic SEM wear studies of tungsten carbide cermets. [friction and wear experiments

Science.gov (United States)

Brainard, W. A.; Buckley, D. H.

1975-01-01

Dynamic friction and wear experiments were conducted in a scanning electron microscope. The wear behavior of pure tungsten carbide and composite with 6 and 15 weight percent cobalt binder was examined, and etching of the binder was done to selectively determine the role of the binder in the wear process. Dynamic experiments were conducted as the tungsten carbide (WC) and bonded WC cermet surfaces were transversed by a 50 micron radiused diamond stylus. These studies show that the predominant wear process in WC is fracture initiated by plastic deformation, and the wear of the etched cermets is similar to pure WC. The presence of the cobalt binder reduces both friction and wear. The cementing action of the cobalt reduces granular separation, and promotes a dense polished layer because of its low shear strength film-forming properties. The wear debris generated from unetched surface is approximately the same composition as the bulk.

Millisecond bearing wear

International Nuclear Information System (INIS)

Blatchley, C.; Sioshansi, P.

1987-01-01

Radionuclides have been widely used for many purposes in medicine, metals, transportation, manufacturing and research. Approximately 200 artificially produced nuclides are commercially available from reactors or accelerator sources. Another 400 or so have properties which may make them useful if satisfactory methods of production can be developed. One of the most economically important industrial applications of radionuclides has been in wear measurement and condition monitoring in reciprocating engines. The general techniques developed for this purpose have also been applied in a number of other areas besides engine or lubrication studies. The wear of floor wax applied to linoleum, for example, has been measured by mixing shortlived radionuclides in the wax. In those applications where the material is tagged and then followed, the radionuclides are termed ''tracers,'' similar to the medical tracer materials used to measure uptake or metabolism of biologically active chemicals in the body. The alternate function for the radionuclides is to act as ''markers'' which indicate the amount of material which is remaining at the location of the original activation. Both approaches require that the debris removed from the surface must be carried away from the original site. The first application of radioactive tracers as a diagnostic tool in engines was in 1949. In this technique, an entire wearing part such as a piston ring or gear was first exposed to neutrons in a nuclear reactor. This caused the entire volume of the part to become radioactive. The part was next installed and exposed to wear in the operating engine. Detectors placed near the oil line, an oil filter or a sediment trap then determined the amount of debris from the part by counting the gamma rays escaping from the debris

Backside wear in modern total knee designs.

Science.gov (United States)

Jayabalan, Prakash; Furman, Bridgette D; Cottrell, Jocelyn M; Wright, Timothy M

2007-02-01

Although modularity affords various options to the orthopedic surgeon, these benefits come at a price. The unintended bearing surface between the back surface of the tibial insert and the metallic tray results in micromotion leading to polyethylene wear debris. The objective of this study was to examine the backside wear of tibial inserts from three modern total knee designs with very different locking mechanisms: Insall-Burstein II (IB II), Optetrak, and Advance. A random sample of 71 inserts were obtained from our institution's retrieval collection and examined to assess the extent of wear, depth of wear, and wear damage modes. Patient records were also obtained to determine patient age, body mass index, length of implantation, and reason for revision. Modes of wear damage (abrasion, burnishing, scratching, delamination, third body debris, surface deformation, and pitting) were then scored in each zone from 0 to 3 (0 = 0%, 1 = 0-10%, 2 = 10-50%, and 3 = >50%). The depth of wear was subjectively identified as removal of manufacturing identification markings stamped onto the inferior surface of the polyethylene. Both Advance and IB II polyethylene inserts showed significantly higher scores for backside wear than the Optetrak inserts. All IB II and Advance implants showed evidence of backside wear, whereas 17% (5 out of 30) of the retrieved Optetrak implants had no observable wear. There were no significant differences when comparing the depth of wear score between designs. The locking mechanism greatly affects the propensity for wear and should be considered when choosing a knee implant system.

Multi technical analysis of wear mechanisms in axial piston pumps

Science.gov (United States)

Schuhler, G.; Jourani, A.; Bouvier, S.; Perrochat, J.-M.

2017-05-01

Axial piston pumps convert a motor rotation motion into hydraulic or pneumatic power. Their compactness and efficiency of approximately 0.9 make them suitable for actuation applications especially in aeronautics. However, they suffer a limited life due to the wear of their components. In the literature, studies of axial piston pumps deal with contact between its different elements under lubrication conditions. Nevertheless, they are more focused on analytic or numerical approaches. This study consists in an experimental analysis of worn pump components to highlight and understand wear mechanisms. Piston shoes are central components in the axial piston pump since they are involved in three tribological contacts. These three contacts are thereby studied: piston shoes/swashplate, piston shoes/pistons and piston shoes/shoes hold down plate (SHDP). To perform this analysis, helicopter hydraulic pumps after different operating times have been studied. The wear damage mechanisms and wear debris are analysed using SEM observations. 3D surface roughness measurements are then used to characterize worn surfaces. The observations reveal that in the contact between shoes and swashplate, the main wear mechanism is three-body abrasive wear due to coarse carbides removal. Between shoes and pistons, wear occurs in a less severe way and is mainly due to the debris generated in the first contact and conveyed by the lubricating fluid. In the third contact, the debris are also the prime cause of the abrasive wear and the generation of deep craters in the piston shoes.

Comparison of apical debris extrusion using a conventional and two rotary techniques.

Science.gov (United States)

Adl, Alireza; Sahebi, Safoora; Moazami, Fariborz; Niknam, Mahnaz

2009-01-01

Preparation techniques and instruments produce and push debris out of canals. This can induce inflammation within the periapical area. Therefore, instrumentation that causes less extrusion of debris is more desirable. The purpose of this in vitro study was to evaluate the quantity of debris extruded from the apical foramen during root canal preparation by using one hand, and two rotary instrumentation techniques. Three different groups each with 12 mesiobuccal roots of human maxillary first molar were instrumented using either step-back technique with hand instruments, FlexMaster or Mtwo rotary system. Debris extruded from the apical foramen during canal preparation was collected. The mean dry weights of debris were compared using one-way ANOVA. Step-back group had a significantly greater mean weight of debris compared to the other two groups (Pengine driven techniques were associated with less apical debris extrusion. [Iranian Endodontic Journal 2009;4(4):135-8].

Wear mechanisms of toughened zirconias

International Nuclear Information System (INIS)

Becker, P.C.; Libsch, T.A.; Rhee, S.K.

1985-01-01

The dry friction and wear behavior of toughened zirconias against hardened steel was studied using the falex ring and block technique. Three experimental ZrO 2 -Y 2 O 3 ceramics and two commerical ZrO 2 -MgO ceramics were investigated. Each ceramic was tested at 500 and 2000 rpm at normal loads in the range 2.3 to 40.8 kg. Significant trends in the friction and wear data were found correlating composition, test speeds, and loads. Microstructural examination of the ring, ceramic block, and wear debris has shown that the wear process is very complex and incorporates a number of mechanisms

Development of wear-resistant coatings for cobalt-base alloys

International Nuclear Information System (INIS)

Cockeram, B.V.

1999-01-01

The level of nuclear plant radiation exposure due to activated cobalt wear debris could potentially be reduced by covering the cobalt-base materials with a wear resistant coating. Laboratory pin-on-disc and rolling contact wear tests were used to evaluate the wear performance of several coatings. Based on the results of these tests, multilayer Cr-nitride coatings and ion nitriding are the most promising approaches

Turbulence induced Fretting-wear characteristics of steam generator helical tubes

International Nuclear Information System (INIS)

Jhung, Myung Jo; Jo, Jong Chull; Kim, Hho Jung; Yune, Young Gill; Yu, Seon Oh

2005-01-01

This study addresses safety assessment of the potential for fretting-wear damages on steam generator helical tubes due to turbulence-induced vibration in operating nuclear power plants. To get the natural frequency, corresponding mode shape and participation factor, modal analyses are performed for helical type tubes with various conditions. Special emphases are put on the effects of coil diameter and the number of turns on the modal and fretting wear characteristics of tubes. Also, investigated are the effects of external pressure on the tube modal characteristics as well as the effects of turbulence induced vibration on the fretting-wear characteristics of tubes

Particle size reduction in debris flows: Laboratory experiments compared with field data from Inyo Creek, California

Science.gov (United States)

Arabnia, O.; Sklar, L. S.; Mclaughlin, M. K.

2014-12-01

Rock particles in debris flows are reduced in size through abrasion and fracture. Wear of coarse sediments results in production of finer particles, which alter the bulk material rheology and influence flow dynamics and runout distance. Particle wear also affects the size distribution of coarse particles, transforming the initial sediment size distribution produced on hillslopes into that delivered to the fluvial channel network. A better understanding of the controls on particle wear in debris flows would aid in the inferring flow conditions from debris flow deposits, in estimating the initial size of sediments entrained in the flow, and in modeling debris flow dynamics and mapping hazards. The rate of particle size reduction with distance traveled should depend on the intensity of particle interactions with other particles and the flow boundary, and on rock resistance to wear. We seek a geomorphic transport law to predict rate of particle wear with debris flow travel distance as a function of particle size distribution, flow depth, channel slope, fluid composition and rock strength. Here we use four rotating drums to create laboratory debris flows across a range of scales. Drum diameters range from 0.2 to 4.0 m, with the largest drum able to accommodate up to 2 Mg of material, including boulders. Each drum has vanes along the boundary to prevent sliding. Initial experiments use angular clasts of durable granodiorite; later experiments will use less resistant rock types. Shear rate is varied by changing drum rotational velocity. We begin experiments with well-sorted coarse particle size distributions, which are allowed to evolve through particle wear. The fluid is initially clear water, which rapidly acquires fine-grained wear products. After each travel increment all coarse particles (mass > 0.4 g) are weighed individually. We quantify particle wear rates using statistics of size and mass distributions, and by fitting various comminution functions to the data

Wear mechanisms in ceramic hip implants.

Science.gov (United States)

Slonaker, Matthew; Goswami, Tarun

2004-01-01

The wear in hip implants is one of the main causes for premature hip replacements. The wear affects the potential life of the prosthesis and subsequent removals of in vivo implants. Therefore, the objective of this article is to review various joints that show lower wear rates and consequently higher life. Ceramics are used in hip implants and have been found to produce lower wear rates. This article discusses the advantages and disadvantages of ceramics compared to other implant materials. Different types of ceramics that are being used are reviewed in terms of the wear characteristics, debris released, and their size together with other biological factors. In general, the wear rates in ceramics were lower than that of metal-on-metal and metal-on-polyethylene combinations.

Characterization of wear debris from metal-on-metal hip implants during normal wear versus edge-loading conditions.

Science.gov (United States)

Kovochich, Michael; Fung, Ernest S; Donovan, Ellen; Unice, Kenneth M; Paustenbach, Dennis J; Finley, Brent L

2018-04-01

Advantages of second-generation metal-on-metal (MoM) hip implants include low volumetric wear rates and the release of nanosized wear particles that are chemically inert and readily cleared from local tissue. In some patients, edge loading conditions occur, which result in higher volumetric wear. The objective of this study was to characterize the size, morphology, and chemistry of wear particles released from MoM hip implants during normal (40° angle) and edge-loading (65° angle with microseparation) conditions. The mean primary particle size by volume under normal wear was 35 nm (range: 9-152 nm) compared with 95 nm (range: 6-573 nm) under edge-loading conditions. Hydrodynamic diameter analysis by volume showed that particles from normal wear were in the nano- (edge-loading conditions generated particles that ranged from Edge-loading conditions generated more elongated particles (4.5%) (aspect ratio ≥ 2.5) and more CoCr alloy particles (9.3%) compared with normal wear conditions (1.3% CoCr particles). By total mass, edge-loading particles contained approximately 640-fold more cobalt than normal wear particles. Our findings suggest that high wear conditions are a potential risk factor for adverse local tissue effects in MoM patients who experience edge loading. This study is the first to characterize both the physical and chemical characteristics of MoM wear particles collected under normal and edge-loading conditions. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 986-996, 2018. © 2017 Wiley Periodicals, Inc.

PWR control rods wear by vibrations induced by coolant fluid

International Nuclear Information System (INIS)

Reynier, R.

1997-01-01

Flow induced vibrations in pressurised water reactors generate the wear of control rods against their guidance systems. Alternate sliding (at 320 deg. C in water) and impact-sliding tests (at room temperature in air) were carried out on 304 L austenitic stainless steel control rods' claddings. Microstructural analysis were made on the wear scars of the tube specimen using Scanning ELectron Microscopy, microhardness measurements and X-ray diffractometry. The alternate sliding leads to an important mass loss, a strong plastic deformation due to the strain hardening of the surface layers and generates strong compressive residual stresses. These results are specific to a severe wear case. Therefore, the impact-sliding mode induces martensitic phase, a cracked oxide layer and a compressive residual stresses weaker than those created in the alternate sliding case. This type of motion leads to a milder wear of the control rods

Effect of mechanical vibrations on the wear behavior of AZ91 Mg alloy

Science.gov (United States)

Chaturvedi, V.; Pandel, U.; Sharma, A.

2018-02-01

AZ91 Mg alloy is the most promising alloy used for structural applications. The vibration induced methods are effective and economic viable in term of mechanical properties. Sliding wear tests were performed on AZ91 Mg alloy using a pin-on- disc configuration. Wear rates were measured at 5 N and 10N at a sliding velocity of 1m/s for varied frequency within the range of 5- 25Hz and a constant amplitude of 2mm. Microstructures of worn surfaces and wear debris were characterized by field emission scanning electron microscopy (FESEM). It is observed that wear resistance of vibrated AZ91 alloy at 15Hz frequency ad 2mm amplitude was superior than cast AZ91 Mg alloy. Finer grain size and equiaxed grain shape both are important parameters for better wear resistance in vibrated AZ91 Mg alloys. FESEM analysis revealed that wear is considerably affected due to frictional heat generated by the relative motion between AZ91 Mg alloy and EN31 steel surface. No single mechanism was responsible for material loss.

Delamination wear mechanism in gray cast irons

International Nuclear Information System (INIS)

Salehi, M.

2000-01-01

An investigation of the friction and sliding wear of gray cast iron against chromium plated cast irons was carried out on a newly constructed reciprocating friction and wear tester. The tests were the first to be done on the test rig under dry conditions and at the speed of 170 cm/min, and variable loads of 20-260 N for a duration of 15 min. to 3 hours. The gray cast iron surfaces worn by a process of plastic deformation at the subsurface, crack nucleation, and crack growth leading to formation of plate like debris and therefore the delamination theory applies. No evidence of adhesion was observed. This could be due to formation of oxides on the wear surface which prevent adhesion. channel type chromium plating ''picked'' up cast iron from the counter-body surfaces by mechanically trapping cast iron debris on and within the cracks. The removal of the plated chromium left a pitted surface on the cast iron

Influence of contact conditions on vibration induced wear of metals

International Nuclear Information System (INIS)

Hofmann, P.J.; Schettler, T.; Wieling, N.; Steininger, D.A.

1990-01-01

Unfavourable design characteristics of nuclear power plant steam generators and heat exchangers in general may result in vibration induced tube wear. A systematic investigation was performed on the contact conditions which may appear between heat exchanger tubes and tube support structure and the influence of different parameters e.g., normal contact force, on the resulting steady state wear rates. It is concluded that not only are contact forces and sliding distances important in the wear process but also the type of relative motion has a decisive influence on the resulting wear rates. For a certain 'work rate', the wear rate caused by repeated impact motions between tube and tube support structure may be an order of magnitude higher than that caused by only sliding motion. This is the result of different operating wear mechanisms which are discussed in this paper. (orig.)

Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model

Energy Technology Data Exchange (ETDEWEB)

Xiao, Fei; Zhai, Zanjing; Jiang, Chuan; Liu, Xuqiang; Li, Haowei; Qu, Xinhua [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Ouyang, Zhengxiao [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 (China); Fan, Qiming; Tang, Tingting [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Qin, An, E-mail: dr.qinan@gmail.com [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Gu, Dongyun, E-mail: dongyungu@gmail.com [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Engineering Research Center of Digital Medicine and Clinical Translation, Ministry of Education of PR China (China); School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030 (China)

2015-01-01

Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure. - Highlights: • Geraniin suppresses osteoclasts formation and function in vitro. • Geraniin impairs RANKL-induced nuclear factor-κB and ERK signaling pathway. • Geraniin suppresses osteolysis in vivo. • Geraniin may be used for treating osteoclast related diseases.

Biocompatible wear-resistant thick ceramic coating

Directory of Open Access Journals (Sweden)

Vogt Nicola

2016-09-01

Full Text Available Sensitisation to immunologically active elements like chromium, cobalt or nickel and debris particle due to wear are serious problems for patients with metallic implants. We tested the approach of using a hard and thick ceramic coating as a wear-resistant protection of titanium implants, avoiding those sensitisation and foreign body problems. We showed that the process parameters strongly influence the coating porosity and, as a consequence, also its hardness.

Wear debris. An environmental issue in total joint replacement.

Science.gov (United States)

Manley, M T; Serekian, P

1994-01-01

There is a growing concern that osteolytic lesions, often adjacent to otherwise stable implants, are a recent phenomenon caused by some recent change in polyethylene, metal, or other aspect of the total hip construction. This study investigates the possibility that bearings and modular connections used in modern hip replacements are an unappreciated source of particulate debris. Measurements taken from contemporary femoral bearings show a significant mismatch in both surface finish and sphericity of mating metal and polyethylene components, with sphericity of inserts being much worse then sphericity of femoral heads. The tolerances for sphericity of polyethylene inserts were further changed by the placement of an insert into its metal shell. Hip simulator tests of assembled inserts and shells showed greater polyethylene weight loss for metal-backed shells than for inserts alone. Bending and torsional tests of metal/metal modular connections showed that dynamic loads can release large numbers of debris particles from taper junctions. Because osteolytic lesions clearly are associated with overload of tissue by debris particles, the design, manufacture, and tolerances of modular connections in total hip replacement all seem to require reevaluation.

The ocular response to extended wear of a high Dk silicone hydrogel contact lens.

Science.gov (United States)

Fonn, Desmond; MacDonald, Karen E; Richter, Doris; Pritchard, Nicola

2002-05-01

A four-month extended wear clinical trial was conducted to compare the ocular effects of a high Dk Balafilcon A silicone hydrogel lens and a low Dk HEMA 38.6 per cent H20 soft lens. Twenty-four subjects who were adapted to daily wear of soft lenses wore a high Dk lens in one eye and a low Dk HEMA lens in the other eye for four months on an extended wear basis after one week of daily wear. Thirteen progress evaluations were conducted using standard clinical procedures. Eighteen subjects (75 per cent) completed the study. The high Dk lens induced significantly less bulbar and limbal injection and corneal vascularisation than the low Dk HEMA lens (p Dk lens. A significant increase in myopia was found in the eyes wearing the low Dk HEMA lens (mean = 0.50 D, p Dk lens. Three subjects developed small infiltrates in the high Dk lens wearing eyes and significantly more post-lens debris was observed under the high Dk lens. Six subjects developed papillary conjunctivitis in the eye wearing silicone hydrogel lenses but only two of those were discontinued from the study. No hypoxia-related effects were observed with extended wear of the high Dk Balafilcon A silicone hydrogel lens.

Hydrogen ion induced ultralow wear of PEEK under extreme load

Science.gov (United States)

Yan, Shuai; Wang, Anying; Fei, Jixiong; Wang, Zhenyang; Zhang, Xiaofeng; Lin, Bin

2018-03-01

As a high-performance engineering polymer, poly(ether ether ketone) (PEEK) is a perfect candidate material for applications under extreme working conditions. However, its high wear rate greatly shortens its service life. In this study, ultralow friction and wear between PEEK and silicon nitride (Si3N4) under extreme-load conditions (with a mean contact pressure above 100 MPa) are found in acid lubricating solutions. Both friction and wear decrease sharply with decreasing pH. At pH = 1, the friction coefficient decreases by an order of magnitude and the wear rate of the PEEK decreases by two orders of magnitude compared to the results with water lubrication. These reductions in friction and wear occur for different speed, load, and surface roughness conditions. The underlying mechanism can be attributed to the formation of hydrogen-ion-induced electrical double layers on the surfaces of PEEK and Si3N4. The combined effect of the resulting repulsive force, electro-viscosity, and low shear strength of the water layer dramatically reduces both friction and wear.

Adhesion, friction and wear between polytetrafluoroethylene and nitrogen-implanted stainless steel

International Nuclear Information System (INIS)

Yang, E.; Hirvonen, J.P.; Raesaenen, M.; Toivanen, R.O.

1992-01-01

Adhesion, friction and wear of polytetrafluoroethylene (PTFE), carbon-reinforced PTFE, and glass-reinforced PTFE in sliding contact with nitrogen-implanted and unimplanted AISI 316 stainless steel were determined. The transfer of PTFE within the first 10 unidirectional traverses was investigated using the 19 F(p,αγ) 16 O nuclear reaction. External proton beam induced X-ray emission (PIXE) was used to determine the metal transfer from AISI 316 to pin heads. Nitrogen implantation considerably reduced the transfer of PTFE to the steel surface, and the transfer of the metallic elements from stainless steel to the PTFE-based composites. Furthermore, a lower friction coefficient was observed for nitrogen-implanted samples within the first 400 revolutions. The wear of PTFE, glass-reinforced and carbon-reinforced PTFE pins was only slightly reduced on the nitrogen-implanted surface, although a significant improvement in the wear of the steel was observed. Transmission electron microscopy (TEM) examination of wear debris revealed that PTFE was amorphized during the transfer process. However, no change in the structure of the pin head prior to the transfer was detected with an IR spectrophotometer. (orig.)

Dynamic SEM wear studies of tungsten carbide cermets

Science.gov (United States)

Brainard, W. A.; Buckley, D. H.

1975-01-01

Dynamic friction and wear experiments were conducted in a scanning electron microscope. The wear behavior of pure tungsten carbide and composite with 6 and 15 weight percent cobalt binder was examined. Etching of the binder was done to selectively determine the role of the binder in the wear process. Dynamic experiments were conducted as the WC and bonded WC cermet surfaces were transversed by a 50 micron radiused diamond stylus. These studies show that the predominant wear process in WC is fracture initiated by plastic deformation. The wear of the etched cermets is similar to pure WC. The presence of the cobalt binder reduces both friction and wear. The cementing action of the cobalt reduces granular separation and promotes a dense polished layer because of its low shear strength film-forming properties. The wear debris generated from unetched surface is approximately the same composition as the bulk.

Wear behaviour and morphology of stir cast aluminium/SiC nanocomposites

Science.gov (United States)

Tanwir Alam, Md; Arif, Sajjad; Husain Ansari, Akhter

2018-04-01

Wear and friction play a vital role in the service life of components. Aluminium matrix nanocomposites possess tremendous potential for a number of applications in addition to their present uses. It is valuable to the field of newer materials for better performance in tribological applications. In this work, dry sliding wear, friction coefficient and morphology of aluminium alloy (A356) reinforced with silicon carbide nanoparticles (SiCn) were investigated. A356/SiCn nanocomposites (AMNCs) containing 1–5 weight percentage of SiCn were prepared through two-step stir casting process via mechanical ball milling. The wear test was conducted on pin-on-disc test apparatus. Regression analysis was performed to develop mathematical functions to fit the experimental data points. Morphological studies of Al and SiCn as-received, wear debris and worn surfaces were further analysed by SEM along with EDS. The occurrence of oxide layers was observed on worn surfaces. Iron trace was identified by wear debris. It was found that the wear loss and friction coefficient were strongly influenced by mechanical milling and SiCn content. The results exhibited that the friction coefficient reduces with the addition of SiCn as well as with the increase in load. However, wear resistance increases as the reinforcement content increases because of the embedding and wettability effects.

Probiotics protect mice from CoCrMo particles-induced osteolysis

Directory of Open Access Journals (Sweden)

Wang Z

2017-07-01

Full Text Available Zhenheng Wang,* Kaiwen Xue,* Maosheng Bai, Zhantao Deng, Jingjing Gan, Gang Zhou, Hongbo Qian,* Nirong Bao, Jianning Zhao Department of Orthopaedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Wear particle-induced inflammatory osteolysis is the primary cause of aseptic loosening, which is the most common reason for total hip arthroplasty (THA failure in the med- and long term. Recent studies have suggested an important role of gut microbiota (GM in modulating the host metabolism and immune system, leading to alterations in bone mass. Probiotic bacteria administered in adequate amounts can alter the composition of GM and confer health benefits to the host. Given the inflammatory osteolysis that occurs in wear debris-induced prosthesis loosening, we examined whether the probiotic Lactobacillus casei could reduce osteolysis in a mouse calvarial resorption model. In this study, L. casei markedly protected mice from CoCrMo particles (CoPs-induced osteolysis. Osteoclast gene markers and the number of osteoclasts were significantly decreased in L. casei-treated mice. Probiotic treatment decreased the M1-like macrophage phenotype indicated by downregulation of tumor necrosis factor α (TNF-α, interleukin (IL-6 and inducible nitric oxide synthase (iNOS and increased the M2-like macrophage phenotype indicated by upregulation of IL-4, IL-10 and arginase. Collectively, these results indicated that the L. casei treatment modulated the immune status and suppressed wear particle-induced osteolysis in vivo. Thus, probiotic treatment may represent a potential preventive and therapeutic approach to reduced wear debris-induced osteolysis. Keywords: wear particles, gut microbiota, nanotoxicity, macrophage polarization, inflammatory cytokines, aseptic loosening

Gear Tooth Wear Detection Algorithm

Science.gov (United States)

Delgado, Irebert R.

2015-01-01

Vibration-based condition indicators continue to be developed for Health Usage Monitoring of rotorcraft gearboxes. Testing performed at NASA Glenn Research Center have shown correlations between specific condition indicators and specific types of gear wear. To speed up the detection and analysis of gear teeth, an image detection program based on the Viola-Jones algorithm was trained to automatically detect spiral bevel gear wear pitting. The detector was tested using a training set of gear wear pictures and a blind set of gear wear pictures. The detector accuracy for the training set was 75 percent while the accuracy for the blind set was 15 percent. Further improvements on the accuracy of the detector are required but preliminary results have shown its ability to automatically detect gear tooth wear. The trained detector would be used to quickly evaluate a set of gear or pinion pictures for pits, spalls, or abrasive wear. The results could then be used to correlate with vibration or oil debris data. In general, the program could be retrained to detect features of interest from pictures of a component taken over a period of time.

Automotive airborne brake wear debris nanoparticles and cytokinesis-block micronucleus assay in peripheral blood lymphocytes: A pilot study.

Science.gov (United States)

Kazimirova, Alena; Peikertova, Pavlina; Barancokova, Magdalena; Staruchova, Marta; Tulinska, Jana; Vaculik, Miroslav; Vavra, Ivo; Kukutschova, Jana; Filip, Peter; Dusinska, Maria

2016-07-01

Motor vehicle exhaust and non-exhaust processes play a significant role in environmental pollution, as they are a source of the finest particulate matter. Emissions from non-exhaust processes include wear-products of brakes, tires, automotive hardware, road surface, and traffic signs, but still are paid little attention to. Automotive friction composites for brake pads are composite materials which may consist of potentially hazardous materials and there is a lack of information regarding the potential influence of the brake wear debris (BWD) on the environment, especially on human health. Thus, we focused our study on the genotoxicity of the airborne fraction of BWD using a brake pad model representing an average low-metallic formulation available in the EU market. BWD was generated in the laboratory by a full-scale brake dynamometer and characterized by Raman microspectroscopy, scanning electron microscopy, and transmission electron microscopy showing that it contains nano-sized crystalline metal-based particles. Genotoxicity tested in human lymphocytes in different testing conditions showed an increase in frequencies of micronucleated binucleated cells (MNBNCs) exposed for 48h to BWD nanoparticles (NPs) (with 10% of foetal calf serum in culture medium) compared with lymphocytes exposed to medium alone, statistically significant only at the concentration 3µg/cm(2) (p=0.032). Copyright © 2016 Elsevier Inc. All rights reserved.

Onset wear in self-assembled monolayers

International Nuclear Information System (INIS)

D'Acunto, Mario

2006-01-01

Self-assembled monolayers (SAMs) are very useful for the systematic modification of the physical, chemical and structural properties of a surface by varying the chain length, tail group and composition. Many of these properties can be studied making use of atomic force microscopy (AFM), and the interaction between the AFM probe tip and the SAMs can also be considered an excellent reference to study the fundamental properties of dissipation phenomena and onset wear for viscoelastic materials on the nanoscale. We have performed a numerical study showing that the fundamental mechanism for the onset wear is a process of nucleation of domains starting from initial defects. An SAM surface repeatedly sheared by an AFM probe tip with enough applied loads shows the formation of progressive damages nucleating in domains. The AFM induced surface damages involve primarily the formation of radicals from the carbon chain backbones, but the deformations of the chains resulting in changes of period lattice also have to be taken into consideration. The nucleation of the wear domains generally starts at the initial surface defects where the energy cohesion between chains is lower. Moreover, the presence of surface defects is consistent with the changes in lateral force increasing the probability of the activation for the removal of carbon debris from the chain backbone. The quantification of the progressive worn area is performed making use of the Kolmogorov-Johnson-Mehl-Avrami (KJMA) theory for phase transition kinetic processes. The advantage of knowing the general conditions for onset wear on the SAM surfaces can help in studying the fundamental mechanisms for the tribological properties of viscoelastic materials, in solid lubrication applications and biopolymer mechanics

Wear Characteristics of Metallic Biomaterials: A Review

Science.gov (United States)

Hussein, Mohamed A.; Mohammed, Abdul Samad; Al-Aqeeli, Naser

2015-01-01

Metals are extensively used in a variety of applications in the medical field for internal support and biological tissue replacements, such as joint replacements, dental roots, orthopedic fixation, and stents. The metals and alloys that are primarily used in biomedical applications are stainless steels, Co alloys, and Ti alloys. The service period of a metallic biomaterial is determined by its abrasion and wear resistance. A reduction in the wear resistance of the implant results in the release of incompatible metal ions into the body that loosen the implant. In addition, several reactions may occur because of the deposition of wear debris in tissue. Therefore, developing biomaterials with high wear resistance is critical to ensuring a long life for the biomaterial. The aim of this work is to review the current state of knowledge of the wear of metallic biomaterials and how wear is affected by the material properties and conditions in terms of the type of alloys developed and fabrication processes. We also present a brief evaluation of various experimental test techniques and wear characterization techniques that are used to determine the tribological performance of metallic biomaterials.

Effects of wear particles of polyether-ether-ketone and cobalt-chromium-molybdenum on CD4- and CD8-T-cell responses.

Science.gov (United States)

Du, Zhe; Wang, Shujun; Yue, Bing; Wang, Ying; Wang, You

2018-02-16

T-cells, second only to macrophages, are often considered as the potential cells involved in debris-related failure of arthroplasty. Here, we assessed the effects of particulate wear debris on T-cells and inflammatory reactions. Blood samples from 25 donors were incubated with polyether-ether-ketone (PEEK) and cobalt-chromium-molybdenum (CoCrMo) particles generated by custom cryo-milling and pulverization. The T-cell phenotypes were assessed using immunostaining and flow cytometry. For the in vivo study, 0.1 mL of each particle suspension (approximately 1.0 × 10 8 wear particles) was injected into murine knee joints; the synovium and spleen were collected one week after the operation for histological examination and immunofluorescence staining. The T-cell responses observed included low-level activation of Th1, Th2, Th17, and CD8+ pathways after 72 h of co-culture of the particles with peripheral blood mononuclear cells. Obvious CD8+ T-cell responses were observed in local synovium and peripheral spleen, with higher inflammatory cytokine expression in the CoCrMo group. Relatively minor cytotoxic and immunological reactions were observed in vitro , with PEEK and CoCrMo particle-induced immune responses being primarily mediated by CD8+ T-cells, rather than CD4+ T-cells, in vivo . Overall, PEEK wear particles induced fewer inflammatory reactions than CoCrMo particles. This study verified that PEEK was suitable as a potential alternative for metals in total knee replacements in terms of the immunological reaction to PEEK particles, and shed light on the effects of wear particles from polymer and metal-based implants on immune responses.

Advanced non-linear flow-induced vibration and fretting-wear analysis capabilities

Energy Technology Data Exchange (ETDEWEB)

Toorani, M.; Pan, L.; Li, R.; Idvorian, N. [Babcock and Wilcox Canada Ltd., Cambridge, Ontario (Canada); Vincent, B.

2009-07-01

Fretting wear is a potentially significant degradation mechanism in nuclear steam generators and other shell and tube heat transfer equipment as well. This paper presents an overview of the recently developed code FIVDYNA which is used for the non-linear flow-induced vibration and fretting wear analysis for operating steam generators (OTSG and RSG) and shell-and-tube heat exchangers. FIVDYNA is a non-linear time-history Flow-Induced Vibration (FIV) analysis computer program that has been developed by Babcock and Wilcox Canada to advance the understanding of tube vibration and tube to tube-support interaction. In addition to the dynamic fluid induced forces the program takes into account other tube static forces due to axial and lateral tube preload and thermal interaction loads. The program is capable of predicting the location where the fretting wear is most likely to occur and its magnitude taking into account the support geometry including gaps. FIVDYNA uses the general purpose finite element computer code ABAQUS as its solver. Using ABAQUS gives the user the flexibility to add additional forces to the tube ranging from tube preloads and the support offsets to thermal loads. The forces currently being modeled in FIVDYNA are the random turbulence, steady drag force, fluid-elastic forces, support offset and pre-strain force (axial loads). This program models the vibration of tubes and calculates the structural dynamic characteristics, and interaction forces between the tube and the tube supports. These interaction forces are then used to calculate the work rate at the support and eventually the predicted depth of wear scar on the tube. A very good agreement is found with experiments and also other computer codes. (author)

Influence of heat treatment on the wear life of hydraulic fracturing tools

Energy Technology Data Exchange (ETDEWEB)

Zheng, Chao; Liu, Yonghong; Wang, Hanxiang; Qin, Jie; Shen, Yang; Zhang, Shihong [China University of Petroleum, Qingdao (China)

2017-02-15

Wear phenomenon has caused severe damage or failure of fracturing tools in oil and gas industry. In this paper, influence of heat treatment on the mechanical properties and wear resistance of fracturing tool made of lamellar graphite grey cast iron were investigated. The surface composition and microstructure were characterized by X-ray diffraction (XRD) and metallographic microscope. Sliding wear tests were performed to study the tribological behavior. Tests results showed that wear rates of treated specimens decreased by 33 %. Besides, worn morphology and wear debris were analyzed using Scanning electron microscope (SEM) and Energy dispersive Xray spectra (EDS). Wear failure mechanisms of specimens were identified. Furthermore, on-site experiment results indicated that wear loss of treated samples decreased by 37.5 %. The wear life of hydraulic fracturing tools can be improved obviously by the heat treatment.

Influence of heat treatment on the wear life of hydraulic fracturing tools

International Nuclear Information System (INIS)

Zheng, Chao; Liu, Yonghong; Wang, Hanxiang; Qin, Jie; Shen, Yang; Zhang, Shihong

2017-01-01

Wear phenomenon has caused severe damage or failure of fracturing tools in oil and gas industry. In this paper, influence of heat treatment on the mechanical properties and wear resistance of fracturing tool made of lamellar graphite grey cast iron were investigated. The surface composition and microstructure were characterized by X-ray diffraction (XRD) and metallographic microscope. Sliding wear tests were performed to study the tribological behavior. Tests results showed that wear rates of treated specimens decreased by 33 %. Besides, worn morphology and wear debris were analyzed using Scanning electron microscope (SEM) and Energy dispersive Xray spectra (EDS). Wear failure mechanisms of specimens were identified. Furthermore, on-site experiment results indicated that wear loss of treated samples decreased by 37.5 %. The wear life of hydraulic fracturing tools can be improved obviously by the heat treatment

Asperity-Level Origins of Transition from Mild to Severe Wear

Science.gov (United States)

Aghababaei, Ramin; Brink, Tobias; Molinari, Jean-François

2018-05-01

Wear is the inevitable damage process of surfaces during sliding contact. According to the well-known Archard's wear law, the wear volume scales with the real contact area and as a result is proportional to the load. Decades of wear experiments, however, show that this relation only holds up to a certain load limit, above which the linearity is broken and a transition from mild to severe wear occurs. We investigate the microscopic origins of this breakdown and the corresponding wear transition at the asperity level. Our atomistic simulations reveal that the interaction between subsurface stress fields of neighboring contact spots promotes the transition from mild to severe wear. The results show that this interaction triggers the deep propagation of subsurface cracks and the eventual formation of large debris particles, with a size corresponding to the apparent contact area of neighboring contact spots. This observation explains the breakdown of the linear relation between the wear volume and the normal load in the severe wear regime. This new understanding highlights the critical importance of studying contact beyond the elastic limit and single-asperity models.

Investigation on wear characteristic of biopolymer gear

Science.gov (United States)

Ghazali, Wafiuddin Bin Md; Daing Idris, Daing Mohamad Nafiz Bin; Sofian, Azizul Helmi Bin; Basrawi, Mohamad Firdaus bin; Khalil Ibrahim, Thamir

2017-10-01

Polymer is widely used in many mechanical components such as gear. With the world going to a more green and sustainable environment, polymers which are bio based are being recognized as a replacement for conventional polymers based on fossil fuel. The use of biopolymer in mechanical components especially gear have not been fully explored yet. This research focuses on biopolymer for spur gear and whether the conventional method to investigate wear characteristic is applicable. The spur gears are produced by injection moulding and tested on several speeds using a custom test equipment. The wear formation such as tooth fracture, tooth deformation, debris and weight loss was observed on the biopolymer spur gear. It was noted that the biopolymer gear wear mechanism was similar with other type of polymer spur gears. It also undergoes stages of wear which are; running in, linear and rapid. It can be said that the wear mechanism of biopolymer spur gear is comparable to fossil fuel based polymer spur gear, thus it can be considered to replace polymer gears in suitable applications.

Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγ

Directory of Open Access Journals (Sweden)

Ashlee B. Carter

2009-01-01

Full Text Available Mounting evidence suggests that the risk of developing colorectal cancer (CRC is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD or Ulcerative Colitis (UC have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferative and proapoptotic actions in epithelial cells. All of which may decrease the risk for inflammation-induced CRC. This review will focus on the use of orally active, naturally occurring chemopreventive approaches against inflammation-induced CRC that target PPARγ and therefore down-modulate inflammation.

Diclofenac inhibits 27-hydroxycholesterol-induced inflammation.

Science.gov (United States)

Kim, Bo-Young; Son, Yonghae; Eo, Seong-Kug; Park, Young Chul; Kim, Koanhoi

2016-09-23

27-Hydroxycholesterol (27OHChol) is a cholesterol oxidation product that induces inflammation. In the current study we investigated the effects of diclofenac on inflammatory responses caused by 27OHChol using human monocyte/macrophage (THP-1) cells. Transcription and secretion of CCL2, CCL3, and CCL4 chemokines enhanced by 27OHChol were significantly attenuated by diclofenac in a concentration dependent manner. Migrations of monocytic cells and CCR5-positive Jurkat T cells were reduced proportionally to the concentrations of diclofenac. Superproduction of CCL2 and monocytic cell migration induced by 27OHChol plus LPS were significantly attenuated by diclofenac. Diclofenac also attenuated transcription of MMP-9 and release of its active gene product. These results indicate that diclofenac inhibits 27OHChol-induced inflammatory responses, thereby suppressing inflammation in a milieu rich in cholesterol oxidation products. Copyright © 2016 Elsevier Inc. All rights reserved.

NF-κB decoy oligodeoxynucleotide mitigates wear particle-associated bone loss in the murine continuous infusion model.

Science.gov (United States)

Lin, Tzu-Hua; Pajarinen, Jukka; Sato, Taishi; Loi, Florence; Fan, Changchun; Córdova, Luis A; Nabeshima, Akira; Gibon, Emmanuel; Zhang, Ruth; Yao, Zhenyu; Goodman, Stuart B

2016-09-01

Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Wear particle-induced chronic inflammation is associated with the development of periprosthetic osteolysis. Modulation of NF-κB signaling in macrophages, osteoclasts, and mesenchymal stem cells could potentially mitigate this disease. In the current study, we examined the effects of local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) on wear particle-induced bone loss in a murine continuous femoral particle infusion model. Ultra-high molecular weight polyethylene particles (UHMWPE) with or without lipopolysaccharide (LPS) were infused via osmotic pumps into hollow titanium rods placed in the distal femur of mice for 4weeks. Particle-induced bone loss was evaluated by μCT, and immunohistochemical analysis of sections from the femur. Particle infusion alone resulted in reduced bone mineral density and trabecular bone volume fraction in the distal femur. The decoy ODN reversed the particle-associated bone volume fraction loss around the implant, irrespective of the presence of LPS. Particle-infusion with LPS increased bone mineral density in the distal femur compared with particle-infusion alone. NF-κB decoy ODN reversed or further increased the bone mineral density in the femur (3-6mm from the distal end) exposed to particles alone or particles plus LPS. NF-κB decoy ODN also inhibited macrophage infiltration and osteoclast number, but had no significant effects on osteoblast numbers in femurs exposed to wear particles and LPS. Our study suggests that targeting NF-κB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced osteolysis. Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Chronic inflammation is crucial for the development of wear particle-associated bone loss. Modulation of NF-κB signaling in macrophages (pro-inflammatory cells), osteoclasts (bone

GIS-based two-dimensional numerical simulation of rainfall-induced debris flow

Directory of Open Access Journals (Sweden)

C. Wang

2008-02-01

Full Text Available This paper aims to present a useful numerical method to simulate the propagation and deposition of debris flow across the three dimensional complex terrain. A depth-averaged two-dimensional numerical model is developed, in which the debris and water mixture is assumed to be continuous, incompressible, unsteady flow. The model is based on the continuity equations and Navier-Stokes equations. Raster grid networks of digital elevation model in GIS provide a uniform grid system to describe complex topography. As the raster grid can be used as the finite difference mesh, the continuity and momentum equations are solved numerically using the finite difference method. The numerical model is applied to simulate the rainfall-induced debris flow occurred in 20 July 2003, in Minamata City of southern Kyushu, Japan. The simulation reproduces the propagation and deposition and the results are in good agreement with the field investigation. The synthesis of numerical method and GIS makes possible the solution of debris flow over a realistic terrain, and can be used to estimate the flow range, and to define potentially hazardous areas for homes and road section.

Particulate metallic debris in cemented total hip arthroplasty.

Science.gov (United States)

Salvati, E A; Betts, F; Doty, S B

1993-08-01

Several studies conducted by the authors in the last six years demonstrate that the generation of metallic debris is more severe with titanium alloy than with cobalt-chrome alloy femoral components in cemented total hip arthroplasty (THA). The debris is generated from the articulating surface, particularly if entrapped acrylic debris produces three-body wear, and from the stem surface when the component loosens and abrades against fragmented cement. In selected cases in which the titanium metallic debris is copious, premature failure and severe progressive bone loss occurs. Electron microscopy demonstrates that the particles of metallic debris can be extremely small (a few hundredths of 1 micron). They are phagocytized by the macrophages and transported to the phagolysosomes. In this highly corrosive environment, the very high surface area of the particles may release toxic concentrations of the constituents of the alloy intracellularly, probably leading to progressive cell degeneration and death, with subsequent release of intracellular enzymes and ingested metallic debris. This cycle most likely repeats itself, leading to tissue necrosis. The results presented do not support the use of titanium alloy femoral components for cemented THA, particularly for the articulating surface.

Can centrifugation affect the morphology of polyethylene wear debris ?

Czech Academy of Sciences Publication Activity Database

Zolotarevova, E.; Fejfarková, Z.; Entlicher, G.; Lapčíková, Monika; Šlouf, Miroslav; Pokorný, D.; Sosna, A.

2008-01-01

Roč. 265, 11-12 (2008), s. 1914-1917 ISSN 0043-1648 R&D Projects: GA MŠk 2B06096 Institutional research plan: CEZ:AV0Z40500505 Keywords : polyethyelene wear particles * total joint replacement * centrifugation Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.509, year: 2008

Coupled DEM-CFD analyses of landslide-induced debris flows

CERN Document Server

Zhao, Tao

2017-01-01

This book reflects the latest research results in computer modelling of landslide-induced debris flows. The book establishes an understanding of the initiation and propagation mechanisms of landslides by means of numerical simulations, so that mitigation strategies to reduce the long-term losses from landslide hazards can be devised. In this context, the book employs the Discrete Element Method (DEM) and Computational Fluid Dynamics (CFD) to investigate the mechanical and hydraulic behaviour of granular materials involved in landslides – an approach that yields meaningful insights into the flow mechanisms, concerning e.g. the mobilization of sediments, the generation and dissipation of excess pore water pressures, and the evolution of effective stresses. As such, the book provides valuable information, useful methods and robust numerical tools that can be successfully applied in the field of debris flow research.

Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

NARCIS (Netherlands)

Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas

Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced

Vaccine-induced inflammation attenuates the vascular responses to mental stress

NARCIS (Netherlands)

Paine, N.J.; Ring, C.; Bosch, J.A.; Drayson, M.T.; Aldred, S.; Veldhuijzen van Zanten, J.J.C.S.

2014-01-01

Inflammation is associated with poorer vascular function, with evidence to suggest that inflammation can also impair the vascular responses to mental stress. This study examined the effects of vaccine-induced inflammation on vascular responses to mental stress in healthy participants. Eighteen male

Wear behavior of steam generator tubes in nuclear power plant operating condition

International Nuclear Information System (INIS)

Kim, In-Sup; Hong, Jin-Ki; Kim, Hyung-Nam; Jang, Ki-Sang

2003-01-01

Reciprocating sliding wear tests were performed on steam generator tubes materials at steam generator operating temperature. The material surfaces react with oxygen to form oxides. The oxide properties such as formation rate and mechanical properties are varied with the test temperature and alloy composition. So, it is important to investigate the wear properties of each steam generator tube materials in steam generator operating condition. The tests results indicated that the wear coefficient in work rate model of alloy 690 was faster than that of alloy 800. From the scanning electron microscopy observation, the wear scars were similar each other and worn surfaces were covered with oxide layers. It seemed that the oxide layers were formed by wear debris sintering or cold welding and these layer properties affected the wear rate of steam generator tube materials. (author)

Prevention of wear particle-induced osteolysis by a novel V-ATPase inhibitor saliphenylhalamide through inhibition of osteoclast bone resorption.

Directory of Open Access Journals (Sweden)

An Qin

Full Text Available Wear particle-induced peri-implant loosening (Aseptic prosthetic loosening is one of the most common causes of total joint arthroplasty. It is well established that extensive bone destruction (osteolysis by osteoclasts is responsible for wear particle-induced peri-implant loosening. Thus, inhibition of osteoclastic bone resorption should prevent wear particle induced osteolysis and may serve as a potential therapeutic avenue for prosthetic loosening. Here, we demonstrate for the first time that saliphenylhalamide, a new V-ATPase inhibitor attenuates wear particle-induced osteolysis in a mouse calvarial model. In vitro biochemical and morphological assays revealed that the inhibition of osteolysis is partially attributed to a disruption in osteoclast acidification and polarization, both a prerequisite for osteoclast bone resorption. Interestingly, the V-ATPase inhibitor also impaired osteoclast differentiation via the inhibition of RANKL-induced NF-κB and ERK signaling pathways. In conclusion, we showed that saliphenylhalamide affected multiple physiological processes including osteoclast differentiation, acidification and polarization, leading to inhibition of osteoclast bone resorption in vitro and wear particle-induced osteolysis in vivo. The results of the study provide proof that the new generation V-ATPase inhibitors, such as saliphenylhalamide, are potential anti-resorptive agents for treatment of peri-implant osteolysis.

Automotive airborne brake wear debris nanoparticles and cytokinesis-block micronucleus assay in peripheral blood lymphocytes: A pilot study

International Nuclear Information System (INIS)

Kazimirova, Alena; Peikertova, Pavlina; Barancokova, Magdalena; Staruchova, Marta; Tulinska, Jana; Vaculik, Miroslav; Vavra, Ivo; Kukutschova, Jana; Filip, Peter; Dusinska, Maria

2016-01-01

Motor vehicle exhaust and non-exhaust processes play a significant role in environmental pollution, as they are a source of the finest particulate matter. Emissions from non-exhaust processes include wear-products of brakes, tires, automotive hardware, road surface, and traffic signs, but still are paid little attention to. Automotive friction composites for brake pads are composite materials which may consist of potentially hazardous materials and there is a lack of information regarding the potential influence of the brake wear debris (BWD) on the environment, especially on human health. Thus, we focused our study on the genotoxicity of the airborne fraction of BWD using a brake pad model representing an average low-metallic formulation available in the EU market. BWD was generated in the laboratory by a full-scale brake dynamometer and characterized by Raman microspectroscopy, scanning electron microscopy, and transmission electron microscopy showing that it contains nano-sized crystalline metal-based particles. Genotoxicity tested in human lymphocytes in different testing conditions showed an increase in frequencies of micronucleated binucleated cells (MNBNCs) exposed for 48 h to BWD nanoparticles (NPs) (with 10% of foetal calf serum in culture medium) compared with lymphocytes exposed to medium alone, statistically significant only at the concentration 3 µg/cm 2 (p=0.032). - Highlights: • BWD was characterized by Raman microspectroscopy, scanning electron microscopy, and transmission electron microscopy. • Our result showed that BWD contains crystalline metal NPs. • Two different protocols for CBMN assay were used to study of genotoxicity of BWD. • We found significantly increased frequency of MNBNCs after 48 h exposure of BWD (with 10% of foetal calf serum in culture media) at the concentration 3 µg/cm 2 .

Cemented total hip replacement cable debris and acetabular construct durability.

Science.gov (United States)

Altenburg, Aaron J; Callaghan, John J; Yehyawi, Tameem M; Pedersen, Douglas R; Liu, Steve S; Leinen, Jessica A; Dahl, Kevin A; Goetz, Devon D; Brown, Thomas D; Johnston, Richard C

2009-07-01

Third-body wear can adversely affect the outcome of total hip arthroplasty by causing increased polyethylene wear, osteolysis, and component loosening. We hypothesized that there would be greater generation and migration of metal debris to the bearing surfaces in hips in which cobalt-chromium cables were used to reattach the osteotomized greater trochanter when compared with hips in which stainless steel wires were used. Between June 1981 and December 1983, 196 consecutive total hip arthroplasties were performed with use of an Iowa stem and a titanium-backed cemented acetabular component, with cobalt-chromium cable trochanteric reattachment. After nineteen to twenty years of follow-up, the patients were evaluated with regard to the depth of head penetration into the polyethylene (as a surrogate for wear), osteolysis, loosening, and the need for revision. The results were compared with those for a series of 304 total hip arthroplasties that were performed by the same surgeon from January 1984 to December 1985 with use of the same components and the same surgical technique, but with stainless steel wire trochanteric reattachment. The two groups had a comparable nineteen to twenty-year follow-up. All living patients (fifty-nine hips in the cable group and ninety-two hips in the wire group) had minimum ten-year follow-up radiographs. The polyethylene wear rate was 0.101 mm/yr for the cable group and 0.082 mm/yr for the wire group (p = 0.039). For the living patients, the rate of revision of the acetabular component because of aseptic loosening was 37.3% (twenty-two hips) for the cable group and 20.7% (nineteen hips) for the wire group (p = 0.025). The rate of acetabular osteolysis was 44% (twenty-six hips) for the cable group and 26% (twenty-four hips) for the wire group (p = 0.022). Kaplan-Meier analysis with revision of the acetabular component because of aseptic loosening as the end point demonstrated survival rates of 73.7% +/- 9% and 83% +/- 7% for the cable and

Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: Implication in manganese-induced pulmonary inflammation

International Nuclear Information System (INIS)

Han, Jeongoh; Lee, Jong-Suk; Choi, Daekyu; Lee, Youna; Hong, Sungchae; Choi, Jungyun; Han, Songyi; Ko, Yujin; Kim, Jung-Ae; Mi Kim, Young; Jung, Yunjin

2009-01-01

Manganese (II), a transition metal, causes pulmonary inflammation upon environmental or occupational inhalation in excess. We investigated a potential molecular mechanism underlying manganese-induced pulmonary inflammation. Manganese (II) delayed HIF-1α protein disappearance, which occurred by inhibiting HIF-prolyl hydroxylase (HPH), the key enzyme for HIF-1α hydroxylation and subsequent von Hippel-Lindau(VHL)-dependent HIF-1α degradation. HPH inhibition by manganese (II) was neutralized significantly by elevated dose of iron. Consistent with this, the induction of cellular HIF-1α protein by manganese (II) was abolished by pretreatment with iron. Manganese (II) induced the HIF-1 target gene involved in pulmonary inflammation, vascular endothelial growth factor (VEGF), in lung carcinoma cell lines. The induction of VEGF was dependent on HIF-1. Manganese-induced VEGF promoted tube formation of HUVEC. Taken together, these data suggest that HIF-1 may be a potential mediator of manganese-induced pulmonary inflammation

Obesity-induced vascular inflammation involves elevated arginase activity.

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Yao, Lin; Bhatta, Anil; Xu, Zhimin; Chen, Jijun; Toque, Haroldo A; Chen, Yongjun; Xu, Yimin; Bagi, Zsolt; Lucas, Rudolf; Huo, Yuqing; Caldwell, Ruth B; Caldwell, R William

2017-11-01

Obesity-induced vascular dysfunction involves pathological remodeling of the visceral adipose tissue (VAT) and increased inflammation. Our previous studies showed that arginase 1 (A1) in endothelial cells (ECs) is critically involved in obesity-induced vascular dysfunction. We tested the hypothesis that EC-A1 activity also drives obesity-related VAT remodeling and inflammation. Our studies utilized wild-type and EC-A1 knockout (KO) mice made obese by high-fat/high-sucrose (HFHS) diet. HFHS diet induced increases in body weight, fasting blood glucose, and VAT expansion. This was accompanied by increased arginase activity and A1 expression in vascular ECs and increased expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein in both VAT and ECs. HFHS also markedly increased circulating inflammatory monocytes and VAT infiltration by inflammatory macrophages, while reducing reparative macrophages. Additionally, adipocyte size and fibrosis increased and capillary density decreased in VAT. These effects of HFHS, except for weight gain and hyperglycemia, were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor 2-( S )-amino-6-boronohexanoic acid (ABH). In mouse aortic ECs, exposure to high glucose (25 mM) and Na palmitate (200 μM) reduced nitric oxide production and increased A1, TNF-α, VCAM-1, ICAM-1, and MCP-1 mRNA, and monocyte adhesion. Knockout of EC-A1 or ABH prevented these effects. HFHS diet-induced VAT inflammation is mediated by EC-A1 expression/activity. Limiting arginase activity is a possible therapeutic means of controlling obesity-induced vascular and VAT inflammation.

Spred-2 deficiency exacerbates lipopolysaccharide-induced acute lung inflammation in mice.

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Yang Xu

Full Text Available BACKGROUND: Acute respiratory distress syndrome (ARDS is a severe and life-threatening acute lung injury (ALI that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spred-2, a negative regulator of the Ras-Raf-extracellular signal-regulated kinase (ERK-MAPK pathway, in lipopolysaccharide (LPS-induced acute lung inflammation. METHODS: Wild-type (WT mice and Spred-2(-/- mice were exposed to intratracheal LPS (50 µg in 50 µL PBS to induce pulmonary inflammation. After LPS-injection, the lungs were harvested to assess leukocyte infiltration, cytokine and chemokine production, ERK-MAPK activation and immunopathology. For ex vivo experiments, alveolar macrophages were harvested from untreated WT and Spred-2(-/- mice and stimulated with LPS. In in vitro experiments, specific knock down of Spred-2 by siRNA or overexpression of Spred-2 by transfection with a plasmid encoding the Spred-2 sense sequence was introduced into murine RAW264.7 macrophage cells or MLE-12 lung epithelial cells. RESULTS: LPS-induced acute lung inflammation was significantly exacerbated in Spred-2(-/- mice compared with WT mice, as indicated by the numbers of infiltrating leukocytes, levels of alveolar TNF-α, CXCL2 and CCL2 in a later phase, and lung pathology. U0126, a selective MEK/ERK inhibitor, reduced the augmented LPS-induced inflammation in Spred-2(-/- mice. Specific knock down of Spred-2 augmented LPS-induced cytokine and chemokine responses in RAW264.7 cells and MLE-12 cells, whereas Spred-2 overexpression decreased this response in RAW264.7 cells. CONCLUSIONS: The ERK-MAPK pathway is involved in LPS-induced acute lung inflammation. Spred-2 controls

Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation

International Nuclear Information System (INIS)

Gremy, O.

2006-12-01

The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

Endothelial Semaphorin 7A promotes inflammation in seawater aspiration-induced acute lung injury.

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Zhang, Minlong; Wang, Li; Dong, Mingqing; Li, Zhichao; Jin, Faguang

2014-10-28

Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague-Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs) were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF)-1α inhibited the seawater induced increase expression of SEMA7A. Meanwhile, knockdown of SEMA7A by specific siRNA inhibited the seawater induced aberrant inflammation, endothelial cytoskeleton remodeling and endothelial permeability. These results suggest that SEMA7A is critical in the development of lung inflammation and pulmonary edema in seawater aspiration-induced ALI, and may be a therapeutic target for this disease.

Eleutheroside E inhibits doxorubicin-induced inflammation and ...

African Journals Online (AJOL)

Purpose: To identify the effects of eleutheroside E (EE) on apoptosis and inflammation induced by doxorubicin (DOX) in H9c2 cells and to investigate the underlying mechanisms. Methods: The effect of EE on H9c2 cell viability was determined using Cell Counting Kit-8 (CCK8). EE effect on DOX-induced apoptosis and ...

A combined triggering-propagation modeling approach for the assessment of rainfall induced debris flow susceptibility

Science.gov (United States)

Stancanelli, Laura Maria; Peres, David Johnny; Cancelliere, Antonino; Foti, Enrico

2017-07-01

Rainfall-induced shallow slides can evolve into debris flows that move rapidly downstream with devastating consequences. Mapping the susceptibility to debris flow is an important aid for risk mitigation. We propose a novel practical approach to derive debris flow inundation maps useful for susceptibility assessment, that is based on the integrated use of DEM-based spatially-distributed hydrological and slope stability models with debris flow propagation models. More specifically, the TRIGRS infiltration and infinite slope stability model and the FLO-2D model for the simulation of the related debris flow propagation and deposition are combined. An empirical instability-to-debris flow triggering threshold calibrated on the basis of observed events, is applied to link the two models and to accomplish the task of determining the amount of unstable mass that develops as a debris flow. Calibration of the proposed methodology is carried out based on real data of the debris flow event occurred on 1 October 2009, in the Peloritani mountains area (Italy). Model performance, assessed by receiver-operating-characteristics (ROC) indexes, evidences fairly good reproduction of the observed event. Comparison with the performance of the traditional debris flow modeling procedure, in which sediment and water hydrographs are inputed as lumped at selected points on top of the streams, is also performed, in order to assess quantitatively the limitations of such commonly applied approach. Results show that the proposed method, besides of being more process-consistent than the traditional hydrograph-based approach, can potentially provide a more accurate simulation of debris-flow phenomena, in terms of spatial patterns of erosion and deposition as well on the quantification of mobilized volumes and depths, avoiding overestimation of debris flow triggering volume and, thus, of maximum inundation flow depths.

Automotive airborne brake wear debris nanoparticles and cytokinesis-block micronucleus assay in peripheral blood lymphocytes: A pilot study

Energy Technology Data Exchange (ETDEWEB)

Kazimirova, Alena, E-mail: alena.kazimirova@szu.sk [Department of Biology, Faculty of Medicine, Slovak Medical University, Limbova 12, 833 03 Bratislava (Slovakia); Peikertova, Pavlina [Nanotechnology Centre, VŠB – Technical University of Ostrava, 17. listopadu 15, 708 00 Ostrava (Czech Republic); IT4Innovations, VŠB – Technical University of Ostrava, 17. listopadu 15, 708 33 Ostrava-Poruba (Czech Republic); Barancokova, Magdalena; Staruchova, Marta; Tulinska, Jana [Department of Biology, Faculty of Medicine, Slovak Medical University, Limbova 12, 833 03 Bratislava (Slovakia); Vaculik, Miroslav [Nanotechnology Centre, VŠB – Technical University of Ostrava, 17. listopadu 15, 708 00 Ostrava (Czech Republic); Vavra, Ivo [Nanotechnology Centre, VŠB – Technical University of Ostrava, 17. listopadu 15, 708 00 Ostrava (Czech Republic); Institute of Electrical Engineering, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 03 Bratislava (Slovakia); Kukutschova, Jana [Nanotechnology Centre, VŠB – Technical University of Ostrava, 17. listopadu 15, 708 00 Ostrava (Czech Republic); Filip, Peter [Department of Mechanical Engineering and Energy Processes, Southern Illinois University, Lincoln Drive 1263, 62901 Carbondale (United States); Dusinska, Maria [Health Effects Laboratory, Department of Environmental Chemistry, NILU-Norwegian Institute for Air Research, Instituttveien 18, 2007 Kjeller (Norway)

2016-07-15

Motor vehicle exhaust and non-exhaust processes play a significant role in environmental pollution, as they are a source of the finest particulate matter. Emissions from non-exhaust processes include wear-products of brakes, tires, automotive hardware, road surface, and traffic signs, but still are paid little attention to. Automotive friction composites for brake pads are composite materials which may consist of potentially hazardous materials and there is a lack of information regarding the potential influence of the brake wear debris (BWD) on the environment, especially on human health. Thus, we focused our study on the genotoxicity of the airborne fraction of BWD using a brake pad model representing an average low-metallic formulation available in the EU market. BWD was generated in the laboratory by a full-scale brake dynamometer and characterized by Raman microspectroscopy, scanning electron microscopy, and transmission electron microscopy showing that it contains nano-sized crystalline metal-based particles. Genotoxicity tested in human lymphocytes in different testing conditions showed an increase in frequencies of micronucleated binucleated cells (MNBNCs) exposed for 48 h to BWD nanoparticles (NPs) (with 10% of foetal calf serum in culture medium) compared with lymphocytes exposed to medium alone, statistically significant only at the concentration 3 µg/cm{sup 2} (p=0.032). - Highlights: • BWD was characterized by Raman microspectroscopy, scanning electron microscopy, and transmission electron microscopy. • Our result showed that BWD contains crystalline metal NPs. • Two different protocols for CBMN assay were used to study of genotoxicity of BWD. • We found significantly increased frequency of MNBNCs after 48 h exposure of BWD (with 10% of foetal calf serum in culture media) at the concentration 3 µg/cm{sup 2}.

Microstructural characterization of low and high carbon CoCrMo alloy nanoparticles produced by mechanical milling

Science.gov (United States)

Simoes, T. A.; Goode, A. E.; Porter, A. E.; Ryan, M. P.; Milne, S. J.; Brown, A. P.; Brydson, R. M. D.

2014-06-01

CoCrMo alloys are utilised as the main material in hip prostheses. The link between this type of hip prosthesis and chronic pain remains unclear. Studies suggest that wear debris generated in-vivo may be related to post-operative complications such as inflammation. These alloys can contain different amounts of carbon, which improves the mechanical properties of the alloy. However, the formation of carbides could become sites that initiate corrosion, releasing ions and/or particles into the human body. This study analysed the mechanical milling of alloys containing both high and low carbon levels in relevant biological media, as an alternative route to generate wear debris. The results show that low carbon alloys produce significantly more nanoparticles than high carbon alloys. During the milling process, strain induces an fcc to hcp phase transformation. Evidence for cobalt and molybdenum dissolution in the presence of serum was confirmed by ICP-MS and TEM EDX techniques.

An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation.

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Jason E Shoemaker

2015-06-01

Full Text Available Influenza viruses present major challenges to public health, evident by the 2009 influenza pandemic. Highly pathogenic influenza virus infections generally coincide with early, high levels of inflammatory cytokines that some studies have suggested may be regulated in a strain-dependent manner. However, a comprehensive characterization of the complex dynamics of the inflammatory response induced by virulent influenza strains is lacking. Here, we applied gene co-expression and nonlinear regression analysis to time-course, microarray data developed from influenza-infected mouse lung to create mathematical models of the host inflammatory response. We found that the dynamics of inflammation-associated gene expression are regulated by an ultrasensitive-like mechanism in which low levels of virus induce minimal gene expression but expression is strongly induced once a threshold virus titer is exceeded. Cytokine assays confirmed that the production of several key inflammatory cytokines, such as interleukin 6 and monocyte chemotactic protein 1, exhibit ultrasensitive behavior. A systematic exploration of the pathways regulating the inflammatory-associated gene response suggests that the molecular origins of this ultrasensitive response mechanism lie within the branch of the Toll-like receptor pathway that regulates STAT1 phosphorylation. This study provides the first evidence of an ultrasensitive mechanism regulating influenza virus-induced inflammation in whole lungs and provides insight into how different virus strains can induce distinct temporal inflammation response profiles. The approach developed here should facilitate the construction of gene regulatory models of other infectious diseases.

Friction and wear properties of novel HDPE--HAp--Al2O3 biocomposites against alumina counterface.

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Bodhak, Subhadip; Nath, Shekhar; Basu, Bikramjit

2009-03-01

In an effort to enhance physical properties of biopolymers (high-density polyethylene, HDPE) in terms of elastic modulus and hardness, various ceramic fillers, like alumina (Al2O3) and hydroxyapatite (HAp) are added, and therefore it is essential to assess the friction and wear resistance properties of HDPE biocomposites. In this perspective, HDPE composites with varying ceramic filler content (upto 40 vol%) were fabricated under the optimal compression molding conditions and their friction and wear properties were evaluated against Al2O3 at fretting contacts. All the experiments were conducted at a load of 10 N for duration of 100,000 cycles in both dry as well as simulated body fluid (SBF). Such planned set of experiments has been designed to address three important issues: (a) whether the improvement in physical properties (hardness, E-modulus) will lead to corresponding improvement in friction and wear properties; (b) whether the fretting in SBF will provide sufficient lubrication in order to considerably enhance the tribological properties, as compared to that in ambient conditions; and (c) whether the generation of wear debris particles be reduced for various compositionally modified polymer composites, in comparison to unreinforced HDPE. The experimental results indicate the possibility of achieving extremely low coefficient of friction (COF approximately 0.047) as well as higher wear resistance (wear rate in the order of approximately 10(-7) mm3 N(-1) m(-1)) with the newly developed composites in SBF. A low wear depth of 3.5-4 microm is recorded, irrespective of fretting environment. Much effort has been put forward to correlate the friction and wear mechanisms with abrasion, adhesion, and wear debris formation.

Wear of ultra-high molecular weight polyethylene against damaged and undamaged stainless steel and diamond-like carbon-coated counterfaces.

Science.gov (United States)

Firkins, P; Hailey, J L; Fisher, J; Lettington, A H; Butter, R

1998-10-01

The wear of ultra-high molecular weight polyethylene (UHMWPE) in artificial joints and the resulting wear debris-induced osteolysis remains a major clinical concern in the orthopaedic sector. Third-body damage of metallic femoral heads is often cited as a cause of accelerated polyethylene wear, and the use of ceramic femoral heads in the hip is gaining increasing favour. In the knee prostheses and for smaller diameter femoral heads, the application of hard surface coatings, such as diamond-like carbon, is receiving considerable attention. However, to date, there has been little or no investigation of the tribology of these coatings in simulated biological environments. In this study, diamond-like carbon (DLC) has been compared to stainless steel in its undamaged form and following simulated third-body damage. The wear of UHMWPE was found to be similar when sliding against undamaged DLC and stainless steel counterfaces. DLC was found to be much more damage resistant than DLC. Under test conditions that simulate third-body damage to the femoral head, the wear of UHMWPE was seven times lower against DLC than against stainless steel (P < 0.05). The study shows DLC has considerable potential as a femoral bearing surface in artificial joints.

Study of the Sensor for On-line Lubricating Oil Debris Monitoring

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Huiqin Zhan

2014-07-01

Full Text Available Mechanical parts such as gears and bearings used in mechanical equipment have a finite lifetime because of corrosion and wear. If the parts are in abnormal operation and is not detected, it may cause catastrophic component failure during operation. One effective approach to detect signs of potential failure of the mechanical equipment is to examine the debris particles in its lubricating oil. This article presented an inductive debris sensor which is designed on the basis of the principle of inductance balance. The structure design and the principle of it are studied. The intensity distribution of its magnetic induction is simulated by the use of simulation software Ansoft Maxwell. The mathematical model when there is a debris particle passing through the sensor is analyzed and the characteristics of the sensor’s induction signal is gotten. Experiments have shown that debris particles can be detected by this sensor.

Monitoring of Non-Ferrous Wear Debris in Hydraulic Oil by Detecting the Equivalent Resistance of Inductive Sensors

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Lin Zeng

2018-03-01

Full Text Available Wear debris in hydraulic oil contains important information on the operation of equipment, which is important for condition monitoring and fault diagnosis in mechanical equipment. A micro inductive sensor based on the inductive coulter principle is presented in this work. It consists of a straight micro-channel and a 3-D solenoid coil wound on the micro-channel. Instead of detecting the inductance change of the inductive sensor, the equivalent resistance change of the inductive sensor is detected for non-ferrous particle (copper particle monitoring. The simulation results show that the resistance change rate caused by the presence of copper particles is greater than the inductance change rate. Copper particles with sizes ranging from 48 μm to 150 μm were used in the experiment, and the experimental results are in good agreement with the simulation results. By detecting the inductive change of the micro inductive sensor, the detection limit of the copper particles only reaches 70 μm. However, the detection limit can be improved to 48 μm by detecting the equivalent resistance of the inductive sensor. The equivalent resistance method was demonstrated to have a higher detection accuracy than conventional inductive detection methods for non-ferrous particle detection in hydraulic oil.

Effect of plasma spraying parameter on wear resistance of NiCrBSiCFe plasma coatings on austenitic stainless steel at elevated temperatures at various loads

International Nuclear Information System (INIS)

Parthasarathi, N.L.; Duraiselvam, Muthukannan; Borah, Utpal

2012-01-01

Highlights: ► Effect of plasma spraying parameters, especially the stand-off distance. ► Effect of microstructure and applied load on coating in sliding wear. ► The reason for maximum wear rate at 250 °C and the minimum wear at 350 °C were explained. ► The worn debris were characterised by SEM analysis and correlated with wear rate. -- Abstract: The dry sliding wear tests were carried out on AISI 316 austenitic stainless steel (ASS) plasma coated with NiCrBSiCFe alloy powder under two set of plasma spraying parameters (PSP-1 and PSP-2). EN 8 medium carbon steel was used as a counterface material. The tests were carried out at loads of 20 N and 40 N with a constant sliding velocity of 1 m/s at room temperature (35°), 150 °C, 250 °C and 350 °C. Metallographic characterisation was carried out by optical microscope (OM), scanning electron microscope (SEM) and X-ray diffraction (XRD). Between the two plasma parameters tested, stand-off distance of 125 mm was found to be more suitable for producing uniform lamellar microstructure with fewer amounts of pores which shows better wear resistance. The wear rate at 250 °C was comparatively more due to the material softening and adhesion by intermolecular bonding. The worn debris collected during sliding at 350 °C turn into oxides which further behaves like a protective and lubricative film eliminating the chances of severe material loss. SEM was used to characterise the worn track and debris to identity the wear mechanism.

STING-IRF3 Triggers Endothelial Inflammation in Response to Free Fatty Acid-Induced Mitochondrial Damage in Diet-Induced Obesity

Science.gov (United States)

Mao, Yun; Luo, Wei; Zhang, Lin; Wu, Weiwei; Yuan, Liangshuai; Xu, Hao; Song, Juhee; Fujiwara, Keigi; Abe, Jun-ichi; LeMaire, Scott A.; Wang, Xing Li; Shen, Ying. H.

2017-01-01

Objective Metabolic stress in obesity induces endothelial inflammation and activation, which initiates adipose tissue inflammation, insulin resistance, and cardiovascular diseases. However, the mechanisms underlying endothelial inflammation induction are not completely understood. Stimulator of interferon genes (STING) is an important molecule in immunity and inflammation. In the present study, we sought to determine the role of STING in palmitic acid (PA)-induced endothelial activation/inflammation. Approach and Results In cultured endothelial cells, PA treatment activated STING, as indicated by its perinuclear translocation and binding to interferon regulatory factor 3 (IRF3), leading to IRF3 phosphorylation and nuclear translocation. The activated IRF3 bound to the promoter of intercellular adhesion molecule 1 (ICAM-1) and induced ICAM-1 expression and monocyte–endothelial cell adhesion. When analyzing the upstream signaling, we found that PA activated STING by inducing mitochondrial damage. PA treatment caused mitochondrial damage and leakage of mitochondrial DNA (mtDNA) into the cytosol. Through the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS), the mitochondrial damage and leaked cytosolic mtDNA activated the STING-IRF3 pathway and increased ICAM-1 expression. In mice with diet-induced obesity, the STING-IRF3 pathway was activated in adipose tissue. However, STING deficiency (Stinggt/gt) partially prevented diet-induced adipose tissue inflammation, obesity, insulin resistance, and glucose intolerance. Conclusions The mitochondrial damage-cGAS-STING-IRF3 pathway is critically involved in metabolic stress-induced endothelial inflammation. STING may be a potential therapeutic target for preventing cardiovascular diseases and insulin resistance in obese individuals. PMID:28302626

Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation

NARCIS (Netherlands)

Hoeger, S.; Bergstraesser, C.; Selhorst, J.; Fontana, J.; Birck, R.; Waldherr, R.; Beck, G.; Sticht, C.; Seelen, M. A.; van Son, W. J.; Leuvenink, H.; Ploeg, R.; Schnuelle, P.; Yard, B. A.

Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability

Microstructure analysis and wear behavior of titanium cermet femoral head with hard TiC layer.

Science.gov (United States)

Luo, Yong; Ge, Shirong; Liu, Hongtao; Jin, Zhongmin

2009-12-11

Titanium cermet was successfully synthesized and formed a thin gradient titanium carbide coating on the surface of Ti6Al4V alloy by using a novel sequential carburization under high temperature, while the titanium cermet femoral head was produced. The titanium cermet phase and surface topography were characterized with X-ray diffraction (XRD) and backscattered electron imaging (BSE). And then the wear behavior of titanium cermet femoral head was investigated by using CUMT II artificial joint hip simulator. The surface characterization indicates that carbon effectively diffused into the titanium alloys and formed a hard TiC layer on the Ti6Al4V alloys surface with a micro-porous structure. The artificial hip joint experimental results show that titanium cermet femoral head could not only improve the wear resistance of artificial femoral head, but also decrease the wear of UHMWPE joint cup. In addition, the carburized titanium alloy femoral head could effectively control the UHMWPE debris distribution, and increase the size of UHMWPE debris. All of the results suggest that titanium cermet is a prospective femoral head material in artificial joint.

A mechanistic understanding of the wear coefficient: From single to multiple asperities contact

Science.gov (United States)

Frérot, Lucas; Aghababaei, Ramin; Molinari, Jean-François

2018-05-01

Sliding contact between solids leads to material detaching from their surfaces in the form of debris particles, a process known as wear. According to the well-known Archard wear model, the wear volume (i.e. the volume of detached particles) is proportional to the load and the sliding distance, while being inversely proportional to the hardness. The influence of other parameters are empirically merged into a factor, referred to as wear coefficient, which does not stem from any theoretical development, thus limiting the predictive capacity of the model. Based on a recent understanding of a critical length-scale controlling wear particle formation, we present two novel derivations of the wear coefficient: one based on Archard's interpretation of the wear coefficient as the probability of wear particle detachment and one that follows naturally from the up-scaling of asperity-level physics into a generic multi-asperity wear model. As a result, the variation of wear rate and wear coefficient are discussed in terms of the properties of the interface, surface roughness parameters and applied load for various rough contact situations. Both new wear interpretations are evaluated analytically and numerically, and recover some key features of wear observed in experiments. This work shines new light on the understanding of wear, potentially opening a pathway for calculating the wear coefficient from first principles.

Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging

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Daniela Frasca

2017-08-01

Full Text Available Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation. We also report data in the literature showing adipose tissue infiltration with immune cells and how these cells are recruited and contribute to local and systemic inflammation. We show that several types of immune cells infiltrate the adipose tissue and these include macrophages, neutrophils, NK cells, innate lymphoid cells, eosinophils, T cells, B1, and B2 cells. Our main focus is how the adipose tissue affects immune responses, in particular B cell responses and antibody production. The role of leptin in generating inflammation and decreased B cell responses is also discussed. We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies.

Study of sapphire probe tip wear when scanning on different materials

International Nuclear Information System (INIS)

Nicolet, Anaïs; Küng, Alain; Meli, Felix

2012-01-01

The accuracy of today's coordinate measuring machines (CMM) has reached a level at which exact knowledge of each component is required. The role of the probe tip is particularly crucial as it is in contact with the sample surface. Understanding how the probe tip wears off will help to narrow the measurement errors. In this work, wear of a sapphire sphere was studied for different scanning conditions and with different sample materials. Wear depth on the probe was investigated using an automated process in situ on the METAS micro-CMM and completed by measurements with an atomic force microscope. We often found a linear dependence between the wear depth and the scan length ranging from 0.5 to 9 nm m −1 , due to variations in scan speed, contact force or sample material. In the case of steel, the wear rate is proportional to the scan speed, while for aluminum several processes seem to interact. A large amount of debris was visible after the tests. Except for aluminum, wear was visible only on the sphere and not on the sample. Sapphire/steel is the worst combination in terms of wear, whereas the combination sapphire/ceramic exhibits almost no wear. (paper)

PIV Visualization of Bubble Induced Flow Circulation in 2-D Rectangular Pool for Ex-Vessel Debris Bed Coolability

Energy Technology Data Exchange (ETDEWEB)

Han, Teayang; Kim, Eunho; Park, Hyun Sun; Moriyama, Kiyofumi [POSTECH, Pohang (Korea, Republic of)

2015-10-15

The previous research works demonstrated the debris bed formation on the flooded cavity floor in experiments. Even in the cases the core melt is once solidified, the debris bed can be re-melted due to the decay heat. If the debris bed is not cooled enough by the coolant, the re-melted debris bed will react with the concrete base mat. This situation is called the molten core-concrete interaction (MCCI) which threatens the integrity of the containment by generated gases which pressurize the containment. Therefore securing the long term coolability of the debris bed in the cavity is crucial. According to the previous research works, the natural convection driven by the rising bubbles affects the coolability and the formation of the debris bed. Therefore, clarification of the natural convection characteristics in and around the debris bed is important for evaluation of the coolability of the debris bed. In this study, two-phase flow around the debris bed in a 2D slice geometry is visualized by PIV method to obtain the velocity map of the flow. The DAVINCI-PIV was developed to investigate the flow around the debris bed. In order to simulate the boiling phenomena induced by the decay heat of the debris bed, the air was injected separately by the air chamber system which consists of the 14 air-flowmeters. The circulation flow developed by the rising bubbles was visualized by PIV method.

Effect of acute moderate exercise on induced inflammation and arterial function in older adults.

Science.gov (United States)

Ranadive, Sushant Mohan; Kappus, Rebecca Marie; Cook, Marc D; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffrey A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

2014-04-01

Acute inflammation reduces flow-mediated vasodilatation and increases arterial stiffness in young healthy individuals. However, this response has not been studied in older adults. The aim of this study, therefore, was to evaluate the effect of acute induced systemic inflammation on endothelial function and wave reflection in older adults. Furthermore, an acute bout of moderate-intensity aerobic exercise can be anti-inflammatory. Taken together, we tested the hypothesis that acute moderate-intensity endurance exercise, immediately preceding induced inflammation, would be protective against the negative effects of acute systemic inflammation on vascular function. Fifty-nine healthy volunteers between 55 and 75 years of age were randomized to an exercise or a control group. Both groups received a vaccine (induced inflammation) and sham (saline) injection in a counterbalanced crossover design. Inflammatory markers, endothelial function (flow-mediated vasodilatation) and measures of wave reflection and arterial stiffness were evaluated at baseline and at 24 and 48 h after injections. There were no significant differences in endothelial function and arterial stiffness between the exercise and control group after induced inflammation. The groups were then analysed together, and we found significant differences in the inflammatory markers 24 and 48 h after induction of acute inflammation compared with sham injection. However, flow-mediated vasodilatation, augmentation index normalized for heart rate (AIx75) and β-stiffness did not change significantly. Our results suggest that acute inflammation induced by influenza vaccination did not affect endothelial function in older adults.

Creatine kinase activity in dogs with experimentally induced acute inflammation

Directory of Open Access Journals (Sweden)

Dimitrinka Zapryanova

2013-01-01

Full Text Available The main purpose of this study was to investigate the effect of acute inflammation on total creatine kinase (CK activity in dogs. In these animals, CK is an enzyme found predominantly in skeletal muscle and significantly elevated serum activity is largely associated with muscle damage. Plasma increases in dogs are associated with cell membrane leakage and will therefore be seen in any condition associated with muscular inflammation. The study was induced in 15 mongrel male dogs (n=9 in experimental group and n=6 in control group at the age of two years and body weight 12-15 kg. The inflammation was reproduced by inoculation of 2 ml turpentine oil subcutaneously in lumbar region. The plasma activity of creatine kinase was evaluated at 0, 6, 24, 48, 72 hours after inoculation and on days 7, 14 and 21 by a kit from Hospitex Diagnostics. In the experimental group, the plasma concentrations of the CK-activity were increased at the 48th hour (97.48±6.92 U/L and remained significantly higher (p<0.05 at the 72 hour (97.43±2.93 U/L compared to the control group (77.08±5.27 U/L. The results of this study suggest that the evaluation of creatine kinase in dogs with experimentally induced acute inflammation has a limited diagnostic value. It was observed that the creatine kinase activity is slightly affected by the experimentally induced acute inflammation in dogs.

Phase stability in wear-induced supersaturated Al-Ti solid solution

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Y.; Yokoyama, K. [Dept. of Functional Machinery Mechanics Shinshu Univ., Ueda (Japan); Hosoda, H. [Precision and Intelligence Lab., Tokyo Inst. of Tech., Nagatsuta, Midori-ku, Yokohama (Japan)

2002-07-01

Al-Ti supersaturated solid solutions were introduced by wear testing and the rapid quenching of an Al/Al{sub 3}Ti composite (part of an Al/Al{sub 3}Ti functionally graded material) that was fabricated using the centrifugal method. The phase stability of the supersaturated solid solution was studied through systematic annealing of the supersaturated solid solution. It was found that the Al-Ti supersaturated solid solution decomposed into Al and Al{sub 3}Ti intermetallic compound phases during the heat treatment. The Al-Ti supersaturated solid solutions fabricated were, therefore, not an equilibrium phase, and thus decomposed into the equilibrium phases during heat treatment. It was also found that heat treatment leads to a significant hardness increase for the Al-Ti supersaturated solid solution. Finally, it was concluded that formation of the wear-induced supersaturated solid solution layer was a result of severe plastic deformation. (orig.)

[Comparison of in vivo characteristics of polyethylene wear particles produced by a metal and a ceramic femoral component in total knee replacement].

Science.gov (United States)

Veigl, D; Vavřík, P; Pokorný, D; Slouf, M; Pavlova, E; Landor, I

2011-01-01

The aim of the study was to evaluate in vivo and compare, in terms of the quality and number of ultra high-molecular polyethylene (UHMWPE) wear particles, total knee replacements of identical construction differing only in the material used for femoral component production, i.e., CoCrMo alloy or ZrO2 ceramics. Samples of peri-prosthetic granuloma tissue were collected in two patients with total knee replacement suffering from implant migration, who were matched in relevant characteristics. The primary knee replacement in Patient 1 with a CoCrMo femoral component was done 7.2 years and in Patient 2 with a ZrO2 implant 6.8 years before this assessment. The polyethylene wear-induced granuloma was analysed by the MORF method enabling us to assess the shape and size of wear debris and the IRc method for assessment of particle concentration. In the granuloma tissue samples of Patient 1, on the average, particles were 0.30 mm in size and their relative volume was 0.19. In the Patient 2 tissue samples, the average size of particles was 0.33 mm and their relative volume was 0.26. There was no significant difference in either particle morphology or their concentration in the granuloma tissue between the two patients. One of the options of how to reduce the production of polyethylene wear particles is to improve the tribological properties of contacting surfaces in total knee replacement by substituting a cobalt-chrome femoral component with a zirconia ceramic femoral component. The previous in vitro testing carried out with a mechanical simulator under conditions approaching real weight-bearing in the human body did show a nearly three-fold decrease in the number of UHMWPE wear particles in zirconia components. The evaluation of granuloma tissue induced by the activity of a real prosthetic joint for nearly seven years, however, did not reveal any great difference in either quality or quantity of polyethylene debris between the two replacements. The difference of surface

A new oil debris sensor for online condition monitoring of wind turbine gearboxes

DEFF Research Database (Denmark)

Wang, Chao; Liu, Hui; Liu, Xiao

2015-01-01

Online Condition Monitoring (CM) is a key technology for the Operation and Maintenance (O&M) of wind turbines. Lubricating oil is the blood of the wind turbine gearbox. Metal debris in lubricating oil contains abundant information regarding the ageing and wear/damage of mechanical transmission sy...

Low grade inflammation inhibits VEGF induced HUVECs migration in p53 dependent manner

International Nuclear Information System (INIS)

Panta, Sushil; Yamakuchi, Munekazu; Shimizu, Toshiaki; Takenouchi, Kazunori; Oyama, Yoko; Koriyama, Toyoyasu; Kojo, Tsuyoshi; Hashiguchi, Teruto

2017-01-01

In the course of studying crosstalk between inflammation and angiogenesis, high doses of pro-inflammatory factors have been reported to induce apoptosis in cells. Under normal circumstances also the pro-inflammatory cytokines are being released in low doses and are actively involved in cell signaling pathways. We studied the effects of low grade inflammation in growth factor induced angiogenesis using tumor necrosis factor alfa (TNFα) and vascular endothelial growth factor A (VEGF) respectively. We found that low dose of TNFα can inhibit VEGF induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Low dose of TNFα induces mild upregulation and moreover nuclear localization of tumor suppressor protein 53 (P53) which causes decrease in inhibitor of DNA binding-1 (Id1) expression and shuttling to the cytoplasm. In absence of Id1, HUVECs fail to upregulate β 3 -integrin and cell migration is decreased. Connecting low dose of TNFα induced p53 to β 3 -integrin through Id1, we present additional link in cross talk between inflammation and angiogenesis. - Highlights: • Low grade inflammation (low dose of TNF alfa) inhibits VEGF induced endothelial cells migration. • The low grade inflammation with VEGF treatment upregulates P53 to a nonlethal level. • P53 activation inhibits Id1 shuttling to the cytoplasm in endothelial cells. • Inhibition of Id1 resulted in downregulation of β 3 -integrin which cause decrease in cell migration. • Inflammation and angiogenesis might cross-talk by P53 – Id1 – β 3 -integrin pathway in endothelial cells.

Glufosinate aerogenic exposure induces glutamate and IL-1 receptor dependent lung inflammation.

Science.gov (United States)

Maillet, Isabelle; Perche, Olivier; Pâris, Arnaud; Richard, Olivier; Gombault, Aurélie; Herzine, Ameziane; Pichon, Jacques; Huaux, Francois; Mortaud, Stéphane; Ryffel, Bernhard; Quesniaux, Valérie F J; Montécot-Dubourg, Céline

2016-11-01

Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1β (IL-1β) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3× per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Quantitative assessment of apical debris extrusion and intracanal debris in the apical third, using hand instrumentation and three rotary instrumentation systems.

Science.gov (United States)

H K, Sowmya; T S, Subhash; Goel, Beena Rani; T N, Nandini; Bhandi, Shilpa H

2014-02-01

Decreased apical extrusion of debris and apical one third debris have strong implications for decreased incidence of postoperative inflammation and pain. Thus, the aim of this study was to assess quantitatively the apical extrusion of debris and intracanal debris in the apical third during root canal instrumentation using hand and three different types of rotary instruments. Sixty freshly extracted single rooted human teeth were randomly divided into four groups. Canal preparation was done using step-back with hand instrumentation, crown-down technique with respect to ProTaper and K3, and hybrid technique with LightSpeed LSX. Irrigation was done with NaOCl, EDTA, and normal saline and for final irrigation, EndoVac system was used. The apically extruded debris was collected on the pre-weighed Millipore plastic filter disk and weighed using microbalance. The teeth were submitted to the histological processing. Sections from the apical third were analyzed by a trinocular research microscope that was coupled to a computer where the images were captured and analyzed using image proplus V4.1.0.0 software. The mean weight of extruded debris for each group and intracanal debris in the root canal was statistically analyzed by a Kruskal-Wallis one-way analysis of variance and Mann-Whitney U test. The result showed that, hand instrumentation using K files showed the highest amount of debris extrusion apically when compared to ProTaper, K3 and LightSpeed LSX. The result also showed that there was no statistically significant difference between the groups in relation to presence of intracanal debris in the apical one third. Based on the results, all instrumentation techniques produced debris extrusion. The engine driven Ni-Ti systems extruded significantly less apical debris than hand instrumentation. There was no statistically significant difference between the groups in relation to presence of intracanal debris in the apical one third.

The common parasite Toxoplasma gondii induces prostatic inflammation and microglandular hyperplasia in a mouse model.

Science.gov (United States)

Colinot, Darrelle L; Garbuz, Tamila; Bosland, Maarten C; Wang, Liang; Rice, Susan E; Sullivan, William J; Arrizabalaga, Gustavo; Jerde, Travis J

2017-07-01

Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model. Male mice were infected systemically with T. gondii parasites and prostatic inflammation was scored based on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation. We found that T. gondii infects the mouse prostate within the first 14 days of infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of proliferative inflammatory microglandular hyperplasia in inflamed mouse prostates. This study identifies the common parasite T. gondii as a new trigger of prostatic inflammation, which we used to develop a novel mouse model of prostatic inflammation. This is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species. Furthermore, T. gondii-induced prostatic inflammation persists and progresses without genetic manipulation in mice, offering a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia. © 2017 Wiley Periodicals, Inc.

Swarm slide - debris flow disaster induced by extreme rainfall in Hiroshima, August 2014 and lessons learnt in urban designing

Science.gov (United States)

Fukuoka, H.; Wang, C.

2015-12-01

Hiroshima city was hit by swarm debris flows along a narrow, and linear-shaped rain band of 2 km x 10 km which appeared in the early morning of August 20, 2014. Most of the flows were induced by shallow slide in the upstream. This disaster claimed 74 death, although this city experienced very similar disaster in 1999, claiming more than 30 residents lives. In the most severely affected debris flow torrent, more than 50 residents were killed. Most of the casualties arose in the wooden, vulnerable houses constructed in front of the exit of torrents. Points and lessons learnt from the disaster are as follows:1. Authors collected two types of sands from the source scar of the initial debris slides which induced debris flows. Tested by the ring shear apparatus under pore-pressure control condition, clear "Sliding surface liquefaction" was confirmed for both samples even under small normal stress, representing the small thickness of the slides. These results shows even instant excess pore pressure could initiate the slides and trigger slide-induced debris flow byundrained loading onto the torrent deposits.2. Apparently long-term land-use change since 1945 affected and raised the vulnerability of the community. Residential area had expanded into hill-slope (mountainous / semi-mountainous area) especially along the torrents. Those communities were developed on the past debris flow fan.3. As the devastated area is very close to downtown of Hiroshima city, it gave large societal impact to the Japanese citizens. After 1999 Hiroshima debris flow disaster, the Landslide disaster reduction law which intends to promote designation of landslide potential risk zones, was adopted in 2000. Immediately after 2014 disaster, national diet approved revision of the bill to promote rapid completion of the designation over the national territory. MLIT (Ministry of Land, Infrastructure, Tranportation and Tourism) decided to install X-band rain radars at more sites to cover whole city zones

Effects of wearing bio-active material coated fabric against γ-irradiation-induced cellular damaged in Sprague-Dawley rats

International Nuclear Information System (INIS)

Kang, Jung Ae; Kim, Hye Rim; Yoon, Sun Hye; Nam, Sang Hyun; Park, Sang Hyun; Jang, Beom Su; Go, Kyung Chan; Yang, Gwang Wung; Rho, Young Hwan; Park, Hyo Suk

2016-01-01

Ionizing radiation causes cellular damage and death through the direct damage and/or indirectly the production of ROS, which induces oxidative stress. This study was designed to evaluate the in vivo radioprotective effects of a bio-active material coated fabric (BMCF) against γ-irradiation-induced cellular damage in Sprague-Dawley (SD) rats. Healthy male SD rats wore bio-active material coated (concentrations in 10% and 30%) fabric for 7 days after 3 Gy of γ-irradiation. Radioprotective effects were evaluated by performing various biochemical assays including spleen and thymus index, WBC count, hepatic damage marker enzymes [aspartate transaminase (AST) and alanine transaminase (ALT)] in plasma, liver antioxidant enzymes, and mitochondrial activity in muscle. Exposure to γ-irradiation resulted in hepatocellular and immune systemic damage. Gamma-irradiation induced decreases in antioxidant enzymes. However, wearing the BMCF-30% decreased significantly AST and ALT activities in plasma. Furthermore, wearing the BMCF-30% increased SOD (superoxide dismutase) and mitochondrial activity. These results suggest that wearing BMCF offers effective radioprotection against γ-irradiation-induced cellular damage in SD rats

Effects of wearing bio-active material coated fabric against γ-irradiation-induced cellular damaged in Sprague-Dawley rats

Energy Technology Data Exchange (ETDEWEB)

Kang, Jung Ae; Kim, Hye Rim; Yoon, Sun Hye; Nam, Sang Hyun; Park, Sang Hyun; Jang, Beom Su [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Go, Kyung Chan; Yang, Gwang Wung; Rho, Young Hwan; Park, Hyo Suk [Research and Development Center, VENTEX Co. Ltd., Seoul (Korea, Republic of)

2016-09-15

Ionizing radiation causes cellular damage and death through the direct damage and/or indirectly the production of ROS, which induces oxidative stress. This study was designed to evaluate the in vivo radioprotective effects of a bio-active material coated fabric (BMCF) against γ-irradiation-induced cellular damage in Sprague-Dawley (SD) rats. Healthy male SD rats wore bio-active material coated (concentrations in 10% and 30%) fabric for 7 days after 3 Gy of γ-irradiation. Radioprotective effects were evaluated by performing various biochemical assays including spleen and thymus index, WBC count, hepatic damage marker enzymes [aspartate transaminase (AST) and alanine transaminase (ALT)] in plasma, liver antioxidant enzymes, and mitochondrial activity in muscle. Exposure to γ-irradiation resulted in hepatocellular and immune systemic damage. Gamma-irradiation induced decreases in antioxidant enzymes. However, wearing the BMCF-30% decreased significantly AST and ALT activities in plasma. Furthermore, wearing the BMCF-30% increased SOD (superoxide dismutase) and mitochondrial activity. These results suggest that wearing BMCF offers effective radioprotection against γ-irradiation-induced cellular damage in SD rats.

Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1β-induced chronic inflammation.

Science.gov (United States)

Liang, Wen; Lindeman, Jan H; Menke, Aswin L; Koonen, Debby P; Morrison, Martine; Havekes, Louis M; van den Hoek, Anita M; Kleemann, Robert

2014-05-01

The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β (IL-1β), administered by slow-release minipumps) and metabolic dietary triggers (carbohydrate, cholesterol) of inflammation on the progression of bland liver steatosis (BS) to NASH. Transgenic APOE3*Leiden.huCETP (APOE3L.CETP) mice fed a high-fat diet (HFD) developed BS after 10 weeks. Then, inflammatory triggers were superimposed or not (control) for six more weeks. Mouse livers were analyzed with particular emphasis on hallmarks of inflammation which were defined in human liver biopsies with and without NASH. Livers of HFD-treated control mice remained steatotic and did not progress to NASH. All four inflammatory triggers activated hepatic nuclear factor-κB (NF-κB) significantly and comparably (≥5-fold). However, HFD+LPS or HFD+IL-1β did not induce a NASH-like phenotype and caused intrahepatic accumulation of almost exclusively mononuclear cells. By contrast, mice treated with metabolic triggers developed NASH, characterized by enhanced steatosis, hepatocellular hypertrophy, and formation of mixed-type inflammatory foci containing myeloperoxidase-positive granulocytes (neutrophils) as well as mononuclear cells, essentially as observed in human NASH. Specific for the metabolic inducers was an activation of the proinflammatory transcription factor activator protein-1 (AP-1), neutrophil infiltration, and induction of risk factors associated with human NASH, that is, dyslipidemia (by cholesterol) and insulin resistance (by carbohydrate). In conclusion, HFD feeding followed by NF-κB activation per se (LPS, IL-1β) does not promote the transition from BS to NASH. HFD feeding followed by metabolically evoked inflammation induces additional inflammatory components

Critical role of aldehydes in cigarette smoke-induced acute airway inflammation

NARCIS (Netherlands)

van der Toorn, Marco; Slebos, Dirk-Jan; de Bruin, Harold G.; Gras, Renee; Rezayat, Delaram; Jorge, Lucie; Sandra, Koen; van Oosterhout, Antoon J. M.

2013-01-01

Background: Cigarette smoking (CS) is the most important risk factor for COPD, which is associated with neutrophilic airway inflammation. We hypothesize, that highly reactive aldehydes are critical for CS-induced neutrophilic airway inflammation. Methods: BALB/c mice were exposed to CS, water

Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

Science.gov (United States)

Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

2016-05-20

Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

Odours from marine plastic debris induce food search behaviours in a forage fish.

Science.gov (United States)

Savoca, Matthew S; Tyson, Chris W; McGill, Michael; Slager, Christina J

2017-08-16

Plastic pollution is an anthropogenic stressor in marine ecosystems globally. Many species of marine fish (more than 50) ingest plastic debris. Ingested plastic has a variety of lethal and sublethal impacts and can be a route for bioaccumulation of toxic compounds throughout the food web. Despite its pervasiveness and severity, our mechanistic understanding of this maladaptive foraging behaviour is incomplete. Recent evidence suggests that the chemical signature of plastic debris may explain why certain species are predisposed to mistaking plastic for food. Anchovy ( Engraulis sp.) are abundant forage fish in coastal upwelling systems and a critical prey resource for top predators. Anchovy ingest plastic in natural conditions, though the mechanism they use to misidentify plastic as prey is unknown. Here, we presented wild-caught schools of northern anchovy ( Engraulis mordax ) with odour solutions made of plastic debris and clean plastic to compare school-wide aggregation and rheotactic responses relative to food and food odour presentations. Anchovy schools responded to plastic debris odour with increased aggregation and reduced rheotaxis. These results were similar to the effects food and food odour presentations had on schools. Conversely, these behavioural responses were absent in clean plastic and control treatments. To our knowledge, this is the first experimental evidence that adult anchovy use odours to forage. We conclude that the chemical signature plastic debris acquires in the photic zone can induce foraging behaviours in anchovy schools. These findings provide further support for a chemosensory mechanism underlying plastic consumption by marine wildlife. Given the trophic position of forage fish, these findings have considerable implications for aquatic food webs and possibly human health. © 2017 The Author(s).

SIRT1 inactivation induces inflammation through the dysregulation of autophagy in human THP-1 cells

International Nuclear Information System (INIS)

Takeda-Watanabe, Ai; Kitada, Munehiro; Kanasaki, Keizo; Koya, Daisuke

2012-01-01

Highlights: ► SIRT1 inactivation decreases autophagy in THP-1 cell. ► Inhibition of autophagy induces inflammation. ► SIRT1 inactivation induces inflammation through NF-κB activation. ► The p62/Sqstm1 accumulation by impairment of autophagy is related to NF-κB activation. ► SIRT1 inactivation is involved in the activation of mTOR and decreased AMPK activation. -- Abstract: Inflammation plays a crucial role in atherosclerosis. Monocytes/macrophages are some of the cells involved in the inflammatory process in atherogenesis. Autophagy exerts a protective effect against cellular stresses like inflammation, and it is regulated by nutrient-sensing pathways. The nutrient-sensing pathway includes SIRT1, a NAD + -dependent histone deacetylase, which is implicated in the regulation of a variety of cellular processes including inflammation and autophagy. The mechanism through which the dysfunction of SIRT1 contributes to the regulation of inflammation in relation to autophagy in monocytes/macrophages is unclear. In the present study, we demonstrate that treatment with 2-[(2-Hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenethyl)benzamide (Sirtinol), a chemical inhibitor of SIRT1, induces the overexpression of inflammation-related genes such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 through nuclear factor (NF)-κB signaling activation, which is associated with autophagy dysfunction, as shown through p62/Sqstm1 accumulation and decreased expression of light chain (LC) 3 II in THP-1 cells. The autophagy inhibitor, 3-methyladenine, also induces inflammation-related NF-κB activation. In p62/Sqstm1 knockdown cells, Sirtinol-induced inflammation through NF-κB activation is blocked. In addition, inhibition of SIRT1 is involved in the activation of the mammalian target of rapamycin (mTOR) pathway and is implicated in decreased 5′-AMP activated kinase (AMPK) activation, leading to the impairment of autophagy. The mTOR inhibitor, rapamycin, abolishes

SIRT1 inactivation induces inflammation through the dysregulation of autophagy in human THP-1 cells

Energy Technology Data Exchange (ETDEWEB)

Takeda-Watanabe, Ai; Kitada, Munehiro; Kanasaki, Keizo [Diabetology and Endocrinology, Kanazawa Medical University, Kahoku-Gun, Ishikawa (Japan); Koya, Daisuke, E-mail: koya0516@kanazawa-med.ac.jp [Diabetology and Endocrinology, Kanazawa Medical University, Kahoku-Gun, Ishikawa (Japan)

2012-10-12

Highlights: Black-Right-Pointing-Pointer SIRT1 inactivation decreases autophagy in THP-1 cell. Black-Right-Pointing-Pointer Inhibition of autophagy induces inflammation. Black-Right-Pointing-Pointer SIRT1 inactivation induces inflammation through NF-{kappa}B activation. Black-Right-Pointing-Pointer The p62/Sqstm1 accumulation by impairment of autophagy is related to NF-{kappa}B activation. Black-Right-Pointing-Pointer SIRT1 inactivation is involved in the activation of mTOR and decreased AMPK activation. -- Abstract: Inflammation plays a crucial role in atherosclerosis. Monocytes/macrophages are some of the cells involved in the inflammatory process in atherogenesis. Autophagy exerts a protective effect against cellular stresses like inflammation, and it is regulated by nutrient-sensing pathways. The nutrient-sensing pathway includes SIRT1, a NAD{sup +}-dependent histone deacetylase, which is implicated in the regulation of a variety of cellular processes including inflammation and autophagy. The mechanism through which the dysfunction of SIRT1 contributes to the regulation of inflammation in relation to autophagy in monocytes/macrophages is unclear. In the present study, we demonstrate that treatment with 2-[(2-Hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenethyl)benzamide (Sirtinol), a chemical inhibitor of SIRT1, induces the overexpression of inflammation-related genes such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6 through nuclear factor (NF)-{kappa}B signaling activation, which is associated with autophagy dysfunction, as shown through p62/Sqstm1 accumulation and decreased expression of light chain (LC) 3 II in THP-1 cells. The autophagy inhibitor, 3-methyladenine, also induces inflammation-related NF-{kappa}B activation. In p62/Sqstm1 knockdown cells, Sirtinol-induced inflammation through NF-{kappa}B activation is blocked. In addition, inhibition of SIRT1 is involved in the activation of the mammalian target of rapamycin (mTOR) pathway and

Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation

Energy Technology Data Exchange (ETDEWEB)

Saber, Anne T.; Bornholdt, Jette; Dybdahl, Marianne; Sharma, Anoop K.; Vogel, Ulla; Wallin, Haakan [National Institute of Occupational Health, Copenhagen (Denmark); Loft, Steffen [Copenhagen University, Institute of Public Health, Copenhagen (Denmark)

2005-03-01

Particle-induced carcinogenicity is not well understood, but might involve inflammation. The proinflammatory cytokine tumor necrosis factor (TNF) is considered to be an important mediator in inflammation. We investigated its role in particle-induced inflammation and DNA damage in mice with and without TNF signaling. TNF-/- mice and TNF+/+ mice were exposed by inhalation to 20 mg m{sup -3} carbon black (CB), 20 mg m{sup -3} diesel exhaust particles (DEP), or filtered air for 90 min on each of four consecutive days. DEP, but not CB particles, induced infiltration of neutrophilic granulocutes into the lung lining fluid (by the cellular fraction in the bronchoalveolar lavage fluid), and both particle types induced interleukin-6 mRNA in the lung tissue. Surprisingly, TNF-/- mice were intact in these inflammatory responses. There were more DNA strand breaks in the BAL cells of DEP-exposed TNF-/- mice and CB-exposed mice compared with the air-exposed mice. Thus, the CB-induced DNA damage in BAL-cells was independent of neutrophil infiltration. The data indicate that an inflammatory response was not a prerequisite for DNA damage, and TNF was not required for the induction of inflammation by DEP and CB particles. (orig.)

Development of wear-resistant coatings for cobalt-base alloys

International Nuclear Information System (INIS)

Cockeram, B.V.

1999-01-01

The costs and hazards resulting from nuclear plant radiation exposure with activated cobalt wear debris could potentially be reduced by covering the cobalt-base materials with a wear resistant coating. However, the hardnesses of many cobalt-base wear alloys are significantly lower than conventional PVD hard coatings, and mechanical support of the hard coating is a concern. Four approaches have been taken to minimize the hardness differences between the substrate and PVD hard coating: (1) use a thin Cr-nitride hard coating with layers that are graded with respect to hardness, (2) use a thicker, multilayered coating (Cr-nitride or Zr-nitride) with graded layers, (3) use nitriding to harden the alloy subsurface followed by application of a multilayered coating of Cr-nitride, and (4) use of nitriding alone. Since little work has been done on application of PVD hard coatings to cobalt-base alloys, some details on process development and characterization of the coatings is presented. Scratch testing was used to evaluate the adhesion of the different coatings. A bench-top rolling contact test was used to evaluate the wear resistance of the coatings. The test results are discussed, and the more desirable coating approaches are identified

Erosion by sliding wear in granular flows: Experiments with realistic contact forces

Science.gov (United States)

Stark, C. P.; Hung, C. Y.; Smith, B.; Li, L.; Grinspun, E.; Capart, H.

2015-12-01

Debris flow erosion is a powerful and sometimes dominant process in steep channels. Despite its importance, this phenomenon is relatively little studied in the lab. The large drum experiments of Hsu are a notable exception, in which almost-field-scale impact forces were generated at the head of a synthetic debris flow whose properties (grain size, proportion of fines, etc) were varied widely.A key challenge in these and similar experiments is to explore how erosion rate varies as a function of the scale of the flow (thereby varying inertial stresses, impact forces, etc). The geometrical limitations of most lab experiments, and their short run time, severely limit the scope of such explorations.We achieve this scale exploration in a set of drum erosion experiments by varying effective gravity across several orders of magnitude (1g, 10g, 100g) in a geotechnical centrifuge. By half-filling our 40cm-diameter drum with dry 2.3mm grains, placing a synthetic rock plate at the back and a glass plate at the front 3cm apart, and rotating the drum at 1-50rpm, we simulate wear in a channelized dry granular flow. In contrast to Hsu's experiments, we focus on sliding wear erosion at the flow boundary rather than impact/frictional wear at the flow head. By varying effective gravity from 1g-100g we can tune the pressure exerted by the grains at the boundary without having to change the scale of our apparatus. Using a recently developed depth-averaged, kinetic-energy closure theory for granular flow, we can simultaneously tune the drum rotation rate such that the flow dynamics remain invariant. We can thereby explore how changing the scale of a granular flow, and thus the contact forces of grains on the boundary, controls the rate of rock erosion. Using a small apparatus we can simulate the erosion generated by debris flows several meters deep involving grains up to 10cm in diameter.Our results suggest that sliding wear is the main erosion process, and are consistent with Archard

Debris thickness patterns on debris-covered glaciers

Science.gov (United States)

Anderson, Leif S.; Anderson, Robert S.

2018-06-01

Many debris-covered glaciers have broadly similar debris thickness patterns: surface debris thickens and tends to transition from convex- to concave-up-down glacier. We explain this pattern using theory (analytical and numerical models) paired with empirical observations. Down glacier debris thickening results from the conveyor-belt-like nature of the glacier surface in the ablation zone (debris can typically only be added but not removed) and from the inevitable decline in ice surface velocity toward the terminus. Down-glacier thickening of debris leads to the reduction of sub-debris melt and debris emergence toward the terminus. Convex-up debris thickness patterns occur near the up-glacier end of debris covers where debris emergence dominates (ablation controlled). Concave-up debris thickness patterns occur toward glacier termini where declining surface velocities dominate (velocity controlled). A convex-concave debris thickness profile inevitably results from the transition between ablation-control and velocity-control down-glacier. Debris thickness patterns deviating from this longitudinal shape are most likely caused by changes in hillslope debris supply through time. By establishing this expected debris thickness pattern, the effects of climate change on debris cover can be better identified.

Implant Failure After Motec Wrist Joint Prosthesis Due to Failure of Ball and Socket-Type Articulation-Two Patients With Adverse Reaction to Metal Debris and Polyether Ether Ketone.

Science.gov (United States)

Karjalainen, Teemu; Pamilo, Konsta; Reito, Aleksi

2018-04-21

We describe 2 cases of articulation-related failures resulting in revision surgery after a Motec total wrist arthroplasty: one with an adverse reaction to metal debris and the other with an adverse reaction to polyether ether ketone. In the first patient, blood cobalt and chrome levels were elevated and magnetic resonance imaging showed clear signs of a pseudotumor. The other patient had an extensive release of polyether ether ketone particles into the surrounding synovia due to adverse wear conditions in the cup, leading to the formation of a fluid-filled cyst sac with a black lining and diffuse lymphocyte-dominated inflammation in the synovia. We recommend regular follow-up including x-rays, monitoring of cobalt and chrome ion levels, and a low threshold for cross-sectional imaging in patients who have undergone total wrist arthroplasty with a Motec joint prosthesis. Wear-related problems can also develop in implants in which polyether ether ketone is the bulk material. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Corrosion-wear of β-Ti alloy TMZF (Ti-12Mo-6Zr-2Fe) in simulated body fluid.

Science.gov (United States)

Yang, Xueyuan; Hutchinson, Christopher R

2016-09-15

Titanium alloys are popular metallic implant materials for use in total hip replacements. Although, α+β titanium alloys such as Ti-6Al-4V have been the most commonly used alloys, the high Young's modulus (∼110GPa) leads to an undesirable stress shielding effect. An alternative is to use β titanium alloys that exhibit a significantly lower Young's modulus (∼70GPa). Femoral stems made of a β titanium alloy known as TMZF (Ti-12Mo-6Zr-2Fe (wt.%)) have been used as part of modular hip replacements since the early 2000's but these were recalled in 2011 by the US Food & Drug Administration (FDA) due to unacceptable levels of 'wear debris'. The wear was caused by small relative movement of the stem and neck at the junction where they fit together in the modular hip replacement design. In this study, the corrosion and wear properties of the TMZF alloy were investigated in simulated body fluid to identify the reason for the wear debris generation. Ti64 was used as a control for comparison. It is shown that the interaction between the surfaces of Ti64 and TMZF with simulated body fluid is very similar, both from the point of view of the products formed and the kinetics of the reaction. The dry wear behaviour of TMZF is also close to that of Ti64 and consistent with expectations based on Archard's law for abrasive wear. However, wear of Ti64 and TMZF in simulated body fluid show contrasting behaviours. A type of time-dependent wear test is used to examine the synergy between corrosion and wear of TMZF and Ti64. It is shown that the wear of TMZF accelerated rapidly in SBF whereas that of Ti64 is reduced. The critical role of the strain hardening capacity of the two materials and its role in helping the surface resist abrasion by hydroxyapatite particles formed as a result of the reaction with the SBF is discussed and recommendations are made for modifications that could be made to the TMZF alloy to improve the corrosion-wear response. TMZF is a low modulus β-Ti alloy

Integrating Oil Debris and Vibration Gear Damage Detection Technologies Using Fuzzy Logic

Science.gov (United States)

Dempsey, Paula J.; Afjeh, Abdollah A.

2002-01-01

A diagnostic tool for detecting damage to spur gears was developed. Two different measurement technologies, wear debris analysis and vibration, were integrated into a health monitoring system for detecting surface fatigue pitting damage on gears. This integrated system showed improved detection and decision-making capabilities as compared to using individual measurement technologies. This diagnostic tool was developed and evaluated experimentally by collecting vibration and oil debris data from fatigue tests performed in the NASA Glenn Spur Gear Fatigue Test Rig. Experimental data were collected during experiments performed in this test rig with and without pitting. Results show combining the two measurement technologies improves the detection of pitting damage on spur gears.

Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

NARCIS (Netherlands)

The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; van der Heide, S.; van den Wijngaard, R. M.; de Jonge, W. J.; Boeckxstaens, G. E.

2008-01-01

Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

NARCIS (Netherlands)

The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; Van der Heide, S.; van den Wijngaard, R. M.; Boeckxstaens, G. E.; de Jonge, Wouter J.

Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation; Caracterisation et modulation pharmacologique de l'inflammation intestinale induite par les rayonnements ionisants

Energy Technology Data Exchange (ETDEWEB)

Gremy, O

2006-12-15

The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

Inhibition of Inflammation-Associated Olfactory Loss by Etanercept in an Inducible Olfactory Inflammation Mouse Model.

Science.gov (United States)

Jung, Yong Gi; Lane, Andrew P

2016-06-01

To determine the effect of a soluble human tumor necrosis factor alpha (TNF-α) receptor blocker (etanercept) on an inducible olfactory inflammation (IOI) mouse model. An in vivo study using a transgenic mouse model. Research laboratory. To study the impact of chronic inflammation on the olfactory system, a transgenic mouse model of chronic rhinosinusitis-associated olfactory loss was utilized (IOI mouse), expressing TNF-α in a temporally controlled fashion within the olfactory epithelium. In one group of mice (n = 4), etanercept was injected intraperitoneally (100 μg/dose, 3 times/week) concurrent with a 2-week period of TNF-α expression. A second group of mice (n = 2) underwent induction of TNF-α expression for 8 weeks, with etanercept treatment administered during the final 2 weeks of inflammation. Olfactory function was assayed by elecro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Each group was compared with an equal-number control group. Compared with nontreated IOI mice, etanercept-treated IOI mice showed significantly improved EOG responses after 2 weeks (P loss of olfactory epithelium and no EOG response in nontreated IOI mice. However, in etanercept-treated mice, regeneration of olfactory epithelium was observed. Concomitant administration of etanercept in IOI mice results in interruption of TNF-α-induced olfactory loss and induction of neuroepithelial regeneration. This demonstrates that etanercept has potential utility as a tool for elucidating the role of TNF-α in other olfactory inflammation models. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Bedrock erosion by sliding wear in channelized granular flow

Science.gov (United States)

Hung, C. Y.; Stark, C. P.; Capart, H.; Smith, B.; Maia, H. T.; Li, L.; Reitz, M. D.

2014-12-01

Boundary forces generated by debris flows can be powerful enough to erode bedrock and cause considerable damage to infrastructure during runout. Bedrock wear can be separated into impact and sliding wear processes. Here we focus on sliding wear. We have conducted experiments with a 40-cm-diameter grainflow-generating rotating drum designed to simulate dry channelized debris flows. To generate sliding erosion, we placed a 20-cm-diameter bedrock plate axially on the back wall of the drum. The rotating drum was half filled with 2.3-mm-diameter grains, which formed a thin grain-avalanching layer with peak flow speed and depth close to the drum axis. The whole experimental apparatus was placed on a 100g-ton geotechnical centrifuge and, in order to scale up the stress level, spun to a range of effective gravity levels. Rates and patterns of erosion of the bedrock plate were mapped after each experiment using 3d micro-photogrammetry. High-speed video and particle tracking were employed to measure granular flow dynamics. The resulting data for granular velocities and flow geometry were used to estimate impulse exchanges and forces on the bedrock plate. To address some of the complexities of granular flow under variable gravity levels, we developed a continuum model framed around a GDR MiDi rheology. This model allowed us to scale up boundary forcing while maintaining the same granular flow regime, and helped us to understand important aspects of the flow dynamics including e.g. fluxes of momentum and kinetic energy. In order to understand the detailed processes of boundary forcing, we performed numerical simulations with a new contact dynamics model. This model confirmed key aspects of our continuum model and provided information on second-order behavior such as fluctuations in the forces acting on the wall. By combining these measurements and theoretical analyses, we have developed and calibrated a constitutive model for sliding wear that is a threshold function of

Perinatal programming of metabolic dysfunction and obesity-induced inflammation

DEFF Research Database (Denmark)

Ingvorsen, Camilla; Hellgren, Lars; Pedersen, Susanne Brix

The number of obese women in the childbearing age is drastically increasing globally. As a consequence, more children are born by obese mothers. Unfortunately, maternal obesity and/ or high fat intake during pregnancy increase the risk of developing obesity, type-2 diabetes, cardiovascular disease...... and non-alcoholic fatty liver disease in the children, which passes obesity and metabolic dysfunction on from generation to generation. Several studies try to elucidate causative effects of maternal metabolic markers on the metabolic imprinting in the children; however diet induced obesity is also...... associated with chronic low grade inflammation. Nobody have yet investigated the role of this inflammatory phenotype, but here we demonst rate that obesity induced inflammation is reversed during pregnancy in mice, and is therefore less likely to affect the fetal programming of metabolic dysfunction. Instead...

The impact of cellular debris on Pseudomonas aeruginosa adherence to silicone hydrogel contact lenses and contact lens storage cases.

Science.gov (United States)

Burnham, Geoffrey W; Cavanagh, H Dwight; Robertson, Danielle M

2012-01-01

To evaluate neutrophil-enhanced Pseudomonas aeruginosa (PA) biofilm formation on silicone hydrogel contact lenses and to determine the effect of epithelial biodebris on PA adherence in contact lens storage cases. A fully invasive PA corneal isolate stably conjugated to green fluorescent protein was used. Unworn lotrafilcon A contact lenses were incubated at various ratios of PA to polymorphonuclear neutrophil (PMN) for 24 hours at 37°C. Lens-associated PA was evaluated using laser scanning confocal microscopy and nonviable PA were visualized using propidium iodide. Viable bacteria were enumerated by colony-forming unit (CFU) analysis. For acute epithelial cell studies, PA viability was determined after coincubation with freeze-thaw epithelial cell lysates in 96-well polystyrene plates. Levels of residual cellular debris and bacterial viability were further assessed in used contact lens storage cases. Laser scanning confocal microscopy demonstrated that cotreatment with PMA-stimulated neutrophils increased PA adherence over 24 hours to lens surfaces with a striking alteration of PA architecture. Propidium iodide staining showed that the adherent bacteria consisted of a mixture of viable and nonviable PA; a PMN-associated increase in viable PA was confirmed by CFU (PA:PMN 0.1:1, P = 0.025; PA:PMN 1:1, P = 0.005). Acute epithelial cell debris studies revealed a significant increase in viable PA in 96-well plates in the presence of epithelial freeze-thaw lysates (PA:debris 1:1, P = 0.002; PA:debris 100:1, P = 0.002). Crystal violet staining of used lens storage cases revealed residual cellular debris at all time points, which was independent of microbial contamination; all lens cases used for periods of 9 months or more were uniformly associated with high levels of viable microorganisms. These results demonstrate that prolonged corneal inflammation with the presence of PMNs when confronted with simultaneous PA challenge in extended contact lens wear has the potential

Macrophage-secreted factors induce adipocyte inflammation and insulin resistance

International Nuclear Information System (INIS)

Permana, Paska A.; Menge, Christopher; Reaven, Peter D.

2006-01-01

Macrophage infiltration into adipose tissue increases with obesity, a condition associated with low-grade inflammation and insulin resistance. We investigated the direct effects of macrophage-secreted factors on adipocyte inflammation and insulin resistance. 3T3-L1 adipocytes incubated with media conditioned by RAW264.7 macrophages (RAW-CM) showed dramatically increased transcription of several inflammation-related genes, greater nuclear factor kappa B (NF-κB) activity, and enhanced binding of U937 monocytes. All of these effects were prevented by co-incubation with pyrrolidinedithiocarbamate, an NF-κB inhibitor. Adipocytes incubated with RAW-CM also released more non-esterified fatty acids and this increased lipolysis was not suppressed by insulin. In addition, RAW-CM treatment decreased insulin-stimulated glucose uptake in adipocytes. Taken together, these results indicate that macrophage-secreted factors induce inflammatory responses and reduce insulin responsiveness in adipocytes. These effects of macrophage-secreted factors on adipocytes may contribute significantly to the systemic inflammation and insulin resistance associated with obesity

Rapid Analyses of Polyetheretherketone Wear Characteristics by Accelerated Wear Testing with Microfabricated Surfaces for Artificial Joint Systems.

Science.gov (United States)

Su, Chen-Ying; Kuo, Chien-Wei; Fang, Hsu-Wei

2017-01-01

Wear particle-induced biological responses are the major factors resulting in the loosening and then failure of total joint arthroplasties. It is feasible to improve the lubrication and reduce the wear of artificial joint system. Polyetheretherketone (PEEK) is considered as a potential bearing material due to its mechanical characteristics of resistance to fatigue strain. The PEEK wear particles have been indicated to be involved in biological responses in vitro, and further studies regarding the wear phenomena and wear particle generation are needed. In this study, we have established an accelerated wear testing system with microfabricated surfaces. Various contact pressures and lubricants have been utilized in the accelerated wear tests. Our results showed that increasing contact pressure resulted in an increase of wear particle sizes and wear rate, and the size of PEEK wear particles can be controlled by the feature size of microfabricated surfaces. These results provided the information rapidly about factors that affect the morphology and amount of PEEK wear particles and can be applied in the future for application of PEEK on the biological articulation system.

Empirical closures for particulate debris bed spreading induced by gas–liquid flow

Energy Technology Data Exchange (ETDEWEB)

Basso, S., E-mail: simoneb@kth.se; Konovalenko, A.; Kudinov, P.

2016-02-15

Highlights: • Experimental study of the debris bed self-leveling phenomenon. • A scaling approach and a non-dimensional model to describe particle flow rate are proposed. • The model is validated against experiments with particles of different properties and at different gas injection conditions. - Abstract: Efficient removal of decay heat from the nuclear reactor core debris is paramount for termination of severe accident progression. One of the strategies is based on melt fragmentation, quenching and cooling in a deep pool of water under the reactor vessel. Geometrical configuration of the debris bed is among the important factors which determine possibility of removing the decay heat from the debris bed by natural circulation of the coolant. For instance, a tall mound-shape debris bed can be non-coolable, while the same debris can be coolable if spread uniformly. Decay heat generates a significant amount of thermal energy which goes to production of steam inside the debris bed. Two-phase flow escaping through the top layer of the bed becomes a source of mechanical energy which can move the particulate debris along the slope of the bed. The motion of the debris will lead to flattening of the bed. Such process is often called “self-leveling” phenomenon. Spreading of the debris bed by the self-leveling process can take significant time, depending on the initial debris bed configuration and other parameters. There is a competition between the time scales for reaching (i) a coolable configuration of the bed, and (ii) onset of dryout and re-melting of the debris. In the previous work we have demonstrated that the rate of particulate debris spreading is determined by local gas velocity and local slope angle of the bed. In this work we develop a scaling approach and a closure for prediction of debris spreading rate based on generalization of available experimental data. We demonstrate that introduced scaling criteria are universal for particles of different

Quantification of UHMWPE wear in periprosthetic tissues of hip arthroplasty: Description of a new method based on IR and comparison with radiographic appearance

Czech Academy of Sciences Publication Activity Database

Šlouf, Miroslav; Pokorný, D.; Entlicher, G.; Dybal, Jiří; Synková, Hana; Lapčíková, Monika; Fejfarková, Z.; Špundová, M.; Veselý, F.; Sosna, A.

2008-01-01

Roč. 265, 5-6 (2008), s. 674-684 ISSN 0043-1648 R&D Projects: GA ČR GA106/04/1118; GA MŠk 2B06096 Institutional research plan: CEZ:AV0Z40500505 Keywords : UHMWPE * isolation of wear debris * quantification of wear particles Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.509, year: 2008

Wear of liquid nitrogen-cooled 440C bearing steels in an oxygen environment

Science.gov (United States)

Chaudhuri, Dilip K.; Verma, Ravi

1988-01-01

This paper presents up-to-date findings of the research being conducted to understand the mechanism of sliding wear in unlubricated 440C bearing steels under oxidative conditions. A sliding wear test rig has been designed and built with a cylinder-on-flat geometry. The equipment is capable of testing specimens under high axial loads and sliding speeds in a simulated LOX environment. Samples of 440C steel, quenched and tempered to a hardness of Rc 56, were tested under a load of 890 N and a sliding speed of 2.05 m/sec for total sliding distances of up to 5.54 km. Flash temperatures during these tests were measured with an IR camera and a fast digital recorder. Microstructural and microanalytical data from the worn surfaces and the debris particles are analyzed extensively, along with wear rates, flash temperatures, surface profiles, hardnesses, and residual stresses, in the context of oxidation and wear theories.

Sliding wear studies of sprayed chromium carbide-nichrome coatings for gas-cooled reactor applications

International Nuclear Information System (INIS)

Li, C.C.; Lai, G.Y.

1978-09-01

Chromium carbide-nichrome coatings being considered for wear protection of some critical components in high-temperature gas-cooled reactors (HTGR's) were investigated. The coatings were deposited either by the detonation gun or the plasma-arc process. Sliding wear tests were conducted on specimens in a button-on-plate arrangement with sliding velocities of 7.1 x 10 -3 and 7.9 mm/s at 816 0 C in a helium environment simulates HTGR primary coolant chemistry. The coatings containing 75 or 80 wt % chromium carbide exhibited excellent wear resistance. As the chromium carbide content decreased from either 80 or 75 to 55 wt %, with a concurrent decrease in coating hardness, wear-resistance deteriorated. The friction and wear behavior of the soft coating was similar to that of the bare metal--showing severe galling and significant amounts of wear debris. The friction characteristics of the hard coating exhibited a strong velocity dependence with high friction coefficients in low sliding velocity tests ad vice versa. Both the soft coating and bare metal showed no dependence on sliding velocity. The wear behavior observed in this study is of adhesive type, and the wear damage is believed to be controlled primarily by the delamination process

Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15

Directory of Open Access Journals (Sweden)

Guojun Zhang

2013-01-01

Full Text Available Background. Acute inflammation and its timely resolution play important roles in the body’s responses to the environmental stimulation. Although IFN-γ is well known for the induction of inflammation, its role in the inflammation resolution is still poorly understood. Methodology and Principal Findings. In this study, we investigated the function of interferon gamma (IFN-γ during the resolution of PMA-induced skin inflammation in vivo. The results revealed that the expression levels of IL-6, TNF-α, and monocyte chemoattractant protein 1 (MCP-1 in skin decreased during the resolution stage of PMA-induced inflammation, while IFN-γ is still maintained at a relatively high level. Neutralization of endogenous IFN-γ led to accelerated reduction of epidermal thickness and decreased epithelial cell proliferation. Similarly, decreased infiltration of inflammatory cells (Gr1+ or CD11b+ cells and a significant reduction of proinflammatory cytokines were also observed upon the blockade of IFN-γ. Furthermore, neutralization of IFN-γ boosted ALOX15 expression of the skin during inflammation resolution. In accordance, application of lipoxin A4 (LXA4, a product of ALOX15 obtained a proresolution effect similar to neutralization of IFN-γ. These results demonstrated that through upregulating ALOX15-LXA4 pathway, blockage of IFN-γ can promote the resolution of PMA-induced skin inflammation.

Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation; Caracterisation et modulation pharmacologique de l'inflammation intestinale induite par les rayonnements ionisants

Energy Technology Data Exchange (ETDEWEB)

Gremy, O

2006-12-15

The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

Astrocyte IKKβ/NF-κB signaling is required for diet-induced obesity and hypothalamic inflammation

Directory of Open Access Journals (Sweden)

J.D. Douglass

2017-04-01

Full Text Available Objective: Obesity and high fat diet (HFD consumption in rodents is associated with hypothalamic inflammation and reactive gliosis. While neuronal inflammation promotes HFD-induced metabolic dysfunction, the role of astrocyte activation in susceptibility to hypothalamic inflammation and diet-induced obesity (DIO remains uncertain. Methods: Metabolic phenotyping, immunohistochemical analyses, and biochemical analyses were performed on HFD-fed mice with a tamoxifen-inducible astrocyte-specific knockout of IKKβ (GfapCreERIkbkbfl/fl, IKKβ-AKO, an essential cofactor of NF-κB-mediated inflammation. Results: IKKβ-AKO mice with tamoxifen-induced IKKβ deletion prior to HFD exposure showed equivalent HFD-induced weight gain and glucose intolerance as Ikbkbfl/fl littermate controls. In GfapCreERTdTomato marker mice treated using the same protocol, minimal Cre-mediated recombination was observed in the mediobasal hypothalamus (MBH. By contrast, mice pretreated with 6 weeks of HFD exposure prior to tamoxifen administration showed substantially increased recombination throughout the MBH. Remarkably, this treatment approach protected IKKβ-AKO mice from further weight gain through an immediate reduction of food intake and increase of energy expenditure. Astrocyte IKKβ deletion after HFD exposure—but not before—also reduced glucose intolerance and insulin resistance, likely as a consequence of lower adiposity. Finally, both hypothalamic inflammation and astrocytosis were reduced in HFD-fed IKKβ-AKO mice. Conclusions: These data support a requirement for astrocytic inflammatory signaling in HFD-induced hyperphagia and DIO susceptibility that may provide a novel target for obesity therapeutics. Keywords: Obesity, Astrocytes, Inflammation, Metabolism, Hypothalamus, Energy homeostasis

Preventive Intra Oral Treatment of Sea Cucumber Ameliorate OVA-Induced Allergic Airway Inflammation.

Science.gov (United States)

Lee, Da-In; Park, Mi-Kyung; Kang, Shin Ae; Choi, Jun-Ho; Kang, Seok-Jung; Lee, Jeong-Yeol; Yu, Hak Sun

2016-01-01

Sea cucumber extracts have potent biological effects, including anti-viral, anti-cancer, antibacterial, anti-oxidant, and anti-inflammation effects. To understand their anti-asthma effects, we induced allergic airway inflammation in mice after 7 oral administrations of the extract. The hyper-responsiveness value in mice with ovalbumin (OVA)-alum-induced asthma after oral injection of sea cucumber extracts was significantly lower than that in the OVA-alum-induced asthma group. In addition, the number of eosinophils in the lungs of asthma-induced mice pre-treated with sea cucumber extract was significantly decreased compared to that of PBS pre-treated mice. Additionally, CD4[Formula: see text]CD25[Formula: see text]Foxp3[Formula: see text]T (regulatory T; Treg) cells significantly increased in mesenteric lymph nodes after 7 administrations of the extract. These results suggest that sea cucumber extract can ameliorate allergic airway inflammation via Treg cell activation and recruitment to the lung.

Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice

International Nuclear Information System (INIS)

Chen, Ying; Li, Cuiying; Weng, Dong; Song, Laiyu; Tang, Wen; Dai, Wujing; Yu, Ye; Liu, Fangwei; Zhao, Ming; Lu, Chunwei; Chen, Jie

2014-01-01

Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentage of Th17 in CD4 + T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice. - Highlights: • Neutralization of IL-17A alleviated silica-induced lung inflammation of early stage. • Neutralization of IL-17A decreased Th17 cells and increased Tregs. • IL-17A mediated the reciprocal relationship of Th17/Tregs by IL-6 and/or IL-1β. • Neutralization of IL-17A delayed silica-induced Th1/Th2 immune response. • Neutralization of IL-17A delayed silica-induced lung

Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice

Energy Technology Data Exchange (ETDEWEB)

Chen, Ying; Li, Cuiying [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China); Weng, Dong [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China); Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai (China); Song, Laiyu; Tang, Wen; Dai, Wujing; Yu, Ye; Liu, Fangwei; Zhao, Ming; Lu, Chunwei [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China); Chen, Jie, E-mail: chenjie@mail.cmu.edu.cn [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China)

2014-02-15

Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentage of Th17 in CD4 + T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice. - Highlights: • Neutralization of IL-17A alleviated silica-induced lung inflammation of early stage. • Neutralization of IL-17A decreased Th17 cells and increased Tregs. • IL-17A mediated the reciprocal relationship of Th17/Tregs by IL-6 and/or IL-1β. • Neutralization of IL-17A delayed silica-induced Th1/Th2 immune response. • Neutralization of IL-17A delayed silica-induced lung

Exercise protects against high-fat diet-induced hypothalamic inflammation

NARCIS (Netherlands)

Yi, Chun-Xia; Al-Massadi, Omar; Donelan, Elizabeth; Lehti, Maarit; Weber, Jon; Ress, Chandler; Trivedi, Chitrang; Müller, Timo D.; Woods, Stephen C.; Hofmann, Susanna M.

2012-01-01

Hypothalamic inflammation is a potentially important process in the pathogenesis of high-fat diet-induced metabolic disorders that has recently received significant attention. Microglia are macrophage-like cells of the central nervous system which are activated by pro-inflammatory signals causing

Evolution of metal-metal wear mechanisms in martensitic steel deposits for recharging

International Nuclear Information System (INIS)

Gualco, Agustin; Svoboda, Hernan G; Surian, Estela S; De Vedia, Luis A

2008-01-01

This work studied metal recharged by welding with a martensitic steel (Cr, Mn, Mo, V and W alloy), deposited with a metal filled tubular wire on a low carbon steel, using semi-automatic welding with a contributing heat of 2 kJ/mm and under a gaseous protection of Ar-2%CO 2 . Transverse cuts were extracted from the welded sample for microstructural characterization, hardness measurement, determination of chemical composition and wear tests. The microstructural characterization was performed using light microscopy (LM) and scanning electron microscopy (SEM), X-Ray diffraction (XRD) and energy dispersive spectroscopy (EDS). The wear tests (metal-metal) were carried out on an Amsler machine in natural flow condition, with 500, 1250 and 2000 N of applied charge. The reference material was SAE 1020 steel. The weight loss curves were determined as a function of the distance run up to 5000 meters for all conditions. Then the test's wear surfaces and debris were analyzed. The microstructure consisted mostly of martensite and a fraction of retained austenite. A pattern of dendritic segregation was observed. The hardness on the wear surface averaged 670 HV 1 . The wear behavior showed a lineal variation between the loss of weight and the distance run, for the different loads applied. The rates of wear for each condition were obtained. The observed wear mechanisms were abrasion and adhesion, with plastic deformation. At low charges, the predominant mechanism was mild oxidative wear and at bigger loads heavy oxidative wear with the presence of zones with adhesion. The oxides formed on the surface of the eroded plate were identified

Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability

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Karin ede Punder

2015-05-01

Full Text Available Chronic non-communicable diseases (NCDs are the leading causes of work absence, disability and mortality worldwide. Most of these diseases are associated with low-grade inflammation. Here we hypothesize that stresses (defined as homeostatic disturbances can induce low-grade inflammation by increasing the availability of water, sodium and energy-rich substances to meet the increased metabolic demand induced by the stressor. One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation. In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state. We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases.

Ten-year in vivo wear measurement of a fully congruent mobile bearing unicompartmental knee arthroplasty.

Science.gov (United States)

Price, A J; Short, A; Kellett, C; Beard, D; Gill, H; Pandit, H; Dodd, C A F; Murray, D W

2005-11-01

Polyethylene particulate wear debris continues to be implicated in the aetiology of aseptic loosening following knee arthroplasty. The Oxford unicompartmental knee arthroplasty employs a spherical femoral component and a fully congruous meniscal bearing to increase contact area and theoretically reduce the potential for polyethylene wear. This study measures the in vivo ten-year linear wear of the device, using a roentgenstereophotogrammetric technique. In this in vivo study, seven medial Oxford unicompartmental prostheses, which had been implanted ten years previously were studied. Stereo pairs of radiographs were acquired for each patient and the films were analysed using a roentgen stereophotogrammetric analysis calibration and a computer-aided design model silhouette-fitting technique. Penetration of the femoral component into the original volume of the bearing was our estimate of linear wear. In addition, eight control patients were examined less than three weeks post-insertion of an Oxford prosthesis, where no wear would be expected. The control group showed no measured wear and suggested a system accuracy of 0.1 mm. At ten years, the mean linear wear rate was 0.02 mm/year. The results from this in vivo study confirm that the device has low ten-year linear wear in clinical practice. This may offer the device a survival advantage in the long term.

Inflammation Induces TDP-43 Mislocalization and Aggregation.

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Ana Sofia Correia

Full Text Available TAR DNA-binding protein 43 (TDP-43 is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Here we report that lipopolysaccharide (LPS-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.

Wear of control rod cluster assemblies and of instrumentation thimbles: first results obtained with the vibrateau wear simulator

International Nuclear Information System (INIS)

Zbinden, M.; Hersant, D.

1993-07-01

Several REP components are affected by a particular sort of damage called impact/sliding wear. This kind of wear, originating from flow induced vibrations, affects loosely supported tubular structures. The main involved components are: - the RCCAs claddings and the guides tubes, - the instrumentation thimbles, - the fuel rods claddings, - the SG tubes. The R and D Division is concerned with studies aiming to understand and to master the phenomena leading to this wear. The MTC Branch is charged of the study of the wear itself. Tests are carried out on wear rigs to understand and to model wear mechanisms. The following work is related to the two first wear tests campaigns on the VIBRATEAU wear simulator: - a reproducibility test series in order to assess the spreading of the experimental results, - a comparative test series on surface treatments used to improve the components war resistance. (authors). 7 figs., 2 tabs., 4 refs

Flow-induced vibration and fretting-wear damage in a moisture separator reheater

International Nuclear Information System (INIS)

Pettigrew, M.J.; Taylor, C.E.; Fisher, N.J.

1996-01-01

Tube failures due to excessive flow-induced vibration were experienced in the tube bundles of moisture separator reheaters in a BWR nuclear station. This paper presents the results of a root cause analysis and covers recommendations for continued operation and for replacement tube bundles. The following tasks are discussed: tube failure analysis; flow velocity distribution calculations; flow-induced vibration analysis with particular emphasis on finned-tubes; fretting-wear testing of a tube and tube-support material combination under simulated operating conditions; field measurements of flow-induced vibration; and development of vibration specifications for replacement tube bundles. The effect of transient operating conditions and of other operational changes such as tube fouling were considered in the analysis. This paper outlines a typical field problem and illustrates the application of flow-induced vibration technology for the solution of a practical problem

Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory.

Science.gov (United States)

Heisler, Jillian M; O'Connor, Jason C

2015-11-01

Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. Published by Elsevier Inc.

Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

Science.gov (United States)

Heisler, Jillian M.; O’Connor, Jason C.

2015-01-01

Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

Wear-Induced Changes in FSW Tool Pin Profile: Effect of Process Parameters

Science.gov (United States)

Sahlot, Pankaj; Jha, Kaushal; Dey, G. K.; Arora, Amit

2018-06-01

Friction stir welding (FSW) of high melting point metallic (HMPM) materials has limited application due to tool wear and relatively short tool life. Tool wear changes the profile of the tool pin and adversely affects weld properties. A quantitative understanding of tool wear and tool pin profile is crucial to develop the process for joining of HMPM materials. Here we present a quantitative wear study of H13 steel tool pin profile for FSW of CuCrZr alloy. The tool pin profile is analyzed at multiple traverse distances for welding with various tool rotational and traverse speeds. The results indicate that measured wear depth is small near the pin root and significantly increases towards the tip. Near the pin tip, wear depth increases with increase in tool rotational speed. However, change in wear depth near the pin root is minimal. Wear depth also increases with decrease in tool traverse speeds. Tool pin wear from the bottom results in pin length reduction, which is greater for higher tool rotational speeds, and longer traverse distances. The pin profile changes due to wear and result in root defect for long traverse distance. This quantitative understanding of tool wear would be helpful to estimate tool wear, optimize process parameters, and tool pin shape during FSW of HMPM materials.

TIM-3 is not essential for development of airway inflammation induced by house dust mite antigens

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Yoshihisa Hiraishi

2016-10-01

Conclusions: Our findings indicate that, in mice, TIM-3 is not essential for development of HDM-induced acute or chronic allergic airway inflammation, although it appears to be involved in reduced lymphocyte recruitment during HDM-induced chronic allergic airway inflammation.

Study on torsional fretting wear behavior of a ball-on-socket contact configuration simulating an artificial cervical disk

International Nuclear Information System (INIS)

Wang, Song; Wang, Fei; Liao, Zhenhua; Wang, Qingliang; Liu, Yuhong; Liu, Weiqiang

2015-01-01

A ball-on-socket contact configuration was designed to simulate an artificial cervical disk in structure. UHMWPE (ultra high molecular weight polyethylene) hot pressed by powders and Ti6Al4V alloy were selected as the material combination of ball and socket. The socket surface was coated by a ~ 500 nm C-DLC (carbon ion implantation-diamond like carbon) mixed layer to improve its surface nano hardness and wear resistance. The torsional fretting wear behavior of the ball-on-socket model was tested at different angular displacements under 25% bovine serum lubrication with an axial force of 100 N to obtain more realistic results with that in vivo. The fretting running regimes and wear damage characteristics as well as wear mechanisms for both ball and socket were studied based on 2D (two dimension) optical microscope, SEM (scanning electron microscope) and 3D (three dimension) profiles. With the increase of angular displacement amplitude from 1° to 7°, three types of T-θ (Torsional torque-angular displacement amplitude) curves (i.e., linear, elliptical and parallelogram loops) corresponding to running regimes of PSR (partial slip regime), MR (mixed regime) and SR (slip regime) were observed and analyzed. Both the central region and the edge zone of the ball and socket were damaged. The worn surfaces were characterized by wear scratches and wear debris. In addition, more severe wear damage and more wear debris appeared on the central region of the socket at higher angular displacement amplitude. The dominant damage mechanism was a mix of surface scratch, adhesive wear and abrasive wear for the UHMWPE ball while that for the coated socket was abrasive wear by PE particles and some polishing and rolling process on the raised overgrown DLC grains. The frictional kinetic behavior, wear type, damage region and damage mechanism for the ball-on-socket model revealed significant differences with those of a ball-on-flat contact while showing better consistency with that of in

Study on torsional fretting wear behavior of a ball-on-socket contact configuration simulating an artificial cervical disk

Energy Technology Data Exchange (ETDEWEB)

Wang, Song [State Key Laboratory of Tribology, Tsinghua University, Beijing 100084 (China); Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Wang, Fei [School of Material Science and Engineering, China University of Mining and Technology, Xuzhou 221116 (China); Liao, Zhenhua [Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Biomechanics and Biotechnology Lab, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); Wang, Qingliang [School of Material Science and Engineering, China University of Mining and Technology, Xuzhou 221116 (China); Liu, Yuhong [State Key Laboratory of Tribology, Tsinghua University, Beijing 100084 (China); Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Liu, Weiqiang, E-mail: weiqliu@hotmail.com [Biomechanics and Biotechnology Lab, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); State Key Laboratory of Tribology, Tsinghua University, Beijing 100084 (China)

2015-10-01

A ball-on-socket contact configuration was designed to simulate an artificial cervical disk in structure. UHMWPE (ultra high molecular weight polyethylene) hot pressed by powders and Ti6Al4V alloy were selected as the material combination of ball and socket. The socket surface was coated by a ~ 500 nm C-DLC (carbon ion implantation-diamond like carbon) mixed layer to improve its surface nano hardness and wear resistance. The torsional fretting wear behavior of the ball-on-socket model was tested at different angular displacements under 25% bovine serum lubrication with an axial force of 100 N to obtain more realistic results with that in vivo. The fretting running regimes and wear damage characteristics as well as wear mechanisms for both ball and socket were studied based on 2D (two dimension) optical microscope, SEM (scanning electron microscope) and 3D (three dimension) profiles. With the increase of angular displacement amplitude from 1° to 7°, three types of T-θ (Torsional torque-angular displacement amplitude) curves (i.e., linear, elliptical and parallelogram loops) corresponding to running regimes of PSR (partial slip regime), MR (mixed regime) and SR (slip regime) were observed and analyzed. Both the central region and the edge zone of the ball and socket were damaged. The worn surfaces were characterized by wear scratches and wear debris. In addition, more severe wear damage and more wear debris appeared on the central region of the socket at higher angular displacement amplitude. The dominant damage mechanism was a mix of surface scratch, adhesive wear and abrasive wear for the UHMWPE ball while that for the coated socket was abrasive wear by PE particles and some polishing and rolling process on the raised overgrown DLC grains. The frictional kinetic behavior, wear type, damage region and damage mechanism for the ball-on-socket model revealed significant differences with those of a ball-on-flat contact while showing better consistency with that of in

Caffeine Mitigates Lung Inflammation Induced by Ischemia-Reperfusion of Lower Limbs in Rats

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Wei-Chi Chou

2015-01-01

Full Text Available Reperfusion of ischemic limbs can induce inflammation and subsequently cause acute lung injury. Caffeine, a widely used psychostimulant, possesses potent anti-inflammatory capacity. We elucidated whether caffeine can mitigate lung inflammation caused by ischemia-reperfusion (IR of the lower limbs. Adult male Sprague-Dawley rats were randomly allocated to receive IR, IR plus caffeine (IR + Caf group, sham-operation (Sham, or sham plus caffeine (n=12 in each group. To induce IR, lower limbs were bilaterally tied by rubber bands high around each thigh for 3 hours followed by reperfusion for 3 hours. Caffeine (50 mg/kg, intraperitoneal injection was administered immediately after reperfusion. Our histological assay data revealed characteristics of severe lung inflammation in the IR group and mild to moderate characteristic of lung inflammation in the IR + Caf group. Total cells number and protein concentration in bronchoalveolar lavage fluid of the IR group were significantly higher than those of the IR + Caf group (P<0.001 and P=0.008, resp.. Similarly, pulmonary concentrations of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2 and pulmonary myeloperoxidase activity of the IR group were significantly higher than those of the IR + Caf group (all P<0.05. These data clearly demonstrate that caffeine could mitigate lung inflammation induced by ischemia-reperfusion of the lower limbs.

Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway

Science.gov (United States)

Zhou, Yang; Fang, Li; Jiang, Lei; Wen, Ping; Cao, Hongdi; He, Weichun; Dai, Chunsun; Yang, Junwei

2012-01-01

Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling. PMID:22761883

Resistance to wear and microstructure of martensitic welds deposits for recharge

International Nuclear Information System (INIS)

Gualco, Agustin; Svoboda, Hernan G; Surian, Estela S; Vedia, Luis A

2006-01-01

This work studied the welding metal for a martensitic steel (alloyed to Cr, Mn, Mo, V and W), deposited with a tubular metal-cored wire with gaseous protection of 82%Ar-18%Co 2 on a low carbon steel using the semi-automatic welding process. Transverse pieces were cut from the welded coupon for microstructural characterization, measurement of hardness profiles, determination of the chemical composition and wear trials. The microstructural characterization was done using optic and scanning electronic microscopes, X-rays diffraction and energy-dispersive X-ray spectroscopy and Vicker microhardness (1 kg.) was measured. The wear trials (metal-metal) were performed in an Amsler machine under pure flow conditions. Different loads were used and the reference material was a SAE 1020 steel. The temperatures for each case were measured and the weight loss curves were defined as a function of the distance run and of the load. After testing the wear surfaces and the debris were measured. The microstructure of the welded deposit mostly consists of martensite and some retained austenite, with a pattern of dendritic segregation, and a hardness on the surface of 612 HVI. A lineal variation between the weight loss and the load applied was obtained as a response to the wear. The following phenomena were observed: abrasion, plastic deformation, oxidation and adhesion to the wear surfaces, as well as a tempering effect in the condition of the biggest load. The wear mechanisms acting on both surfaces were identified (CW)

Interactions between mammalian cells and nano- or micro-sized wear particles: physico-chemical views against biological approaches.

Science.gov (United States)

Prokopovich, Polina

2014-11-01

Total joint arthroplasty (TJA) is a more and more frequent approach for the treatment of end-stage osteoarthritis in young and active adults; it successfully relieves joint pain and improves function significantly enhancing the health-related quality of life. Aseptic loosening and other wear-related complications are some of the most recurrent reasons for revision of TJA. This review focuses on current understanding of the biological reactions to prosthetic wear debris comparing in vivo and in vitro results. Mechanisms of interactions of various types of cells with metal, polymeric and ceramic wear particles are summarised. Alternative views based on multidisciplinary approaches are proposed to consider physico-chemical, surface parameters of wear particles (such as: particle size, geometry and charge) and material (particle chemical composition and its nature) with biological effects (cellular responses). Copyright © 2014 Elsevier B.V. All rights reserved.

Dichotomy in response to indomethacin in uv-C and uv-B induced ultraviolet light inflammation

International Nuclear Information System (INIS)

Eaglstein, W.H.; Marsico, A.R.

1975-01-01

In subjects irradiated with both UV-C and UV-B ultraviolet light (UVL), 10 μg of intradermal indomethacin decreased the redness in all 13 of the UV-B irradiated areas but in only 2 of 13 of the UV-C irradiated areas. Higher doses of intradermal indomethacin (50 μg and 100 μg) decreased the redness produced by UV-C irradiation in 6 subjects. It is suggested that the failure of 10 μg of indomethacin to decrease the redness of the UV-C induced inflammation, while decreasing the redness in the UV-B induced inflammation, is consistent with the possibility that prostaglandins participate in UV-B but not UV-C induced inflammation

Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

Science.gov (United States)

Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2013-07-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

Secretoglobin Superfamily Protein SCGB3A2 Deficiency Potentiates Ovalbumin-Induced Allergic Pulmonary Inflammation

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Taketomo Kido

2014-01-01

Full Text Available Secretoglobin (SCGB 3A2, a cytokine-like secretory protein of small molecular weight, which may play a role in lung inflammation, is predominantly expressed in airway epithelial cells. In order to understand the physiological role of SCGB3A2, Scgb3a2−/− mice were generated and characterized. Scgb3a2−/− mice did not exhibit any overt phenotypes. In ovalbumin- (OVA- induced airway allergy inflammation model, Scgb3a2−/− mice in mixed background showed a decreased OVA-induced airway inflammation, while six times C57BL/6NCr backcrossed congenic Scgb3a2−/− mice showed a slight exacerbation of OVA-induced airway inflammation as compared to wild-type littermates. These results indicate that the loss of SCGB3A2 function was influenced by a modifier gene(s in mixed genetic background and suggest that SCGB3A2 has anti-inflammatory property. The results further suggest the possible use of recombinant human SCGB3A2 as an anti-inflammatory agent.

Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation.

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Connie Slocum

2014-07-01

Full Text Available Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4 agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE(-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE(-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune

Titanium Dioxide Exposure Induces Acute Eosinophilic Lung Inflammation in Rabbits

Science.gov (United States)

CHOI, Gil Soon; OAK, Chulho; CHUN, Bong-Kwon; WILSON, Donald; JANG, Tae Won; KIM, Hee-Kyoo; JUNG, Mannhong; TUTKUN, Engin; PARK, Eun-Kee

2014-01-01

Titanium dioxide (TiO2) is increasingly widely used in industrial, commercial and home products. TiO2 aggravates respiratory symptoms by induction of pulmonary inflammation although the mechanisms have not been well investigated. We aimed to investigate lung inflammation in rabbits after intratracheal instillation of P25 TiO2. One ml of 10, 50 and 250 µg of P25 TiO2 was instilled into one of the lungs of rabbits, chest computed-tomography was performed, and bronchoalveolar lavage (BAL) fluid was collected before, at 1 and 24 h after P25 TiO2 exposure. Changes in inflammatory cells in the BAL fluids were measured. Lung pathological assay was also carried out at 24 h after P25 TiO2 exposure. Ground glass opacities were noted in both lungs 1 h after P25 TiO2 and saline (control) instillation. Although the control lung showed complete resolution at 24 h, the lung exposed to P25 TiO2 showed persistent ground glass opacities at 24 h. The eosinophil counts in BAL fluid were significantly increased after P25 TiO2 exposure. P25 TiO2 induced a dose dependent increase of eosinophils in BAL fluid but no significant differences in neutrophil and lymphocyte cell counts were detected. The present findings suggest that P25 TiO2 induces lung inflammation in rabbits which is associated with eosinophilic inflammation. PMID:24705802

Disc-Donut-Tube wear test report, Phase I

International Nuclear Information System (INIS)

Kowal, K.; Knaus, S.E.

1976-06-01

The report describes a test program which simulated the wear-inducing conditions in the AI Prototype CRBR Steam Generator. This was accomplished by simulating the wear inducing loading and motion of a steam tube against ''disc-donut'' tube spacer plates. It was found that 2- 1 / 4 Cr-1 Mo tubes, wearing against 2- 1 / 4 Cr-l Mo tube spacer plates, seized and galled as deep as .017 inches. Inconel 718 tube spacer plates uniformly wore the tubes as deep as .012 in. Aluminum bronze inserts wore as deep as .003 inches into the tube

Important role of platelets in modulating endotoxin-induced lung inflammation in CFTR-deficient mice.

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Caiqi Zhao

Full Text Available Mutation of CFTR (cystic fibrosis transmembrane conductance regulator leads to cystic fibrosis (CF. Patients with CF develop abnormalities of blood platelets and recurrent lung inflammation. However, whether CFTR-mutated platelets play a role in the development of lung inflammation is elusive. Therefore, we intratracheally challenged wildtype and F508del (a common type of CFTR mutation mice with LPS to observe changes of F508del platelets in the peripheral blood and indexes of lung inflammation (BAL neutrophils and protein levels. Furthermore, we investigated whether or not and how F508del platelets modulate the LPS-induced acute lung inflammation by targeting anti-platelet aggregation, depletion of neutrophils, reconstitution of bone marrow or neutrophils, blockade of P-selectin glycoprotein ligand-1 (PSGL-1, platelet activating factor (PAF, and correction of mutated CFTR trafficking. We found that LPS-challenged F508del mice developed severe thrombocytopenia and had higher levels of plasma TXB2 coincided with neutrophilic lung inflammation relative to wildtype control. Inhibition of F508del platelet aggregation or depletion of F508del neutrophils diminished the LPS-induced lung inflammation in the F508del mice. Moreover, wildtype mice reconstituted with either F508del bone marrow or neutrophils developed worse thrombocytopenia. Blocking PSGL-1, platelet activating factor (PAF, or rectifying trafficking of mutated CFTR in F508del mice diminished and alveolar neutrophil transmigration in the LPS-challenged F508del mice. These findings suggest that F508del platelets and their interaction with neutrophils are requisite for the development of LPS-induced lung inflammation and injury. As such, targeting platelets might be an emerging strategy for dampening recurrent lung inflammation in cystic fibrosis patients.

Transient infection of the zebrafish notochord with E. coli induces chronic inflammation

Directory of Open Access Journals (Sweden)

Mai Nguyen-Chi

2014-07-01

Full Text Available Zebrafish embryos and larvae are now well-established models in which to study infectious diseases. Infections with non-pathogenic Gram-negative Escherichia coli induce a strong and reproducible inflammatory response. Here, we study the cellular response of zebrafish larvae when E. coli bacteria are injected into the notochord and describe the effects. First, we provide direct evidence that the notochord is a unique organ that is inaccessible to leukocytes (macrophages and neutrophils during the early stages of inflammation. Second, we show that notochord infection induces a host response that is characterised by rapid clearance of the bacteria, strong leukocyte recruitment around the notochord and prolonged inflammation that lasts several days after bacteria clearance. During this inflammatory response, il1b is first expressed in macrophages and subsequently at high levels in neutrophils. Moreover, knock down of il1b alters the recruitment of neutrophils to the notochord, demonstrating the important role of this cytokine in the maintenance of inflammation in the notochord. Eventually, infection of the notochord induces severe defects of the notochord that correlate with neutrophil degranulation occurring around this tissue. This is the first in vivo evidence that neutrophils can degranulate in the absence of a direct encounter with a pathogen. Persistent inflammation, neutrophil infiltration and restructuring of the extracellular matrix are defects that resemble those seen in bone infection and in some chondropathies. As the notochord is a transient embryonic structure that is closely related to cartilage and bone and that contributes to vertebral column formation, we propose infection of the notochord in zebrafish larvae as a new model to study the cellular and molecular mechanisms underlying cartilage and bone inflammation.

Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

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Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

2014-01-01

The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

Wear behavior of pressable lithium disilicate glass ceramic.

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Peng, Zhongxiao; Izzat Abdul Rahman, Muhammad; Zhang, Yu; Yin, Ling

2016-07-01

This article reports effects of surface preparation and contact loads on abrasive wear properties of highly aesthetic and high-strength pressable lithium disilicate glass-ceramics (LDGC). Abrasive wear testing was performed using a pin-on-disk device in which LDGC disks prepared with different surface finishes were against alumina pins at different contact loads. Coefficients of friction and wear volumes were measured as functions of initial surface finishes and contact loads. Wear-induced surface morphology changes in both LDGC disks and alumina pins were characterized using three-dimensional laser scanning microscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. The results show that initial surface finishes of LDGC specimens and contact loads significantly affected the friction coefficients, wear volumes and wear-induced surface roughness changes of the material. Both wear volumes and friction coefficients of LDGC increased as the load increased while surface roughness effects were complicated. For rough LDGC surfaces, three-body wear was dominant while for fine LDGC surfaces, two-body abrasive wear played a key role. Delamination, plastic deformation, and brittle fracture were observed on worn LDGC surfaces. The adhesion of LDGC matrix materials to alumina pins was also discovered. This research has advanced our understanding of the abrasive wear behavior of LDGC and will provide guidelines for better utilization and preparation of the material for long-term success in dental restorations. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 968-978, 2016. © 2015 Wiley Periodicals, Inc.

Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung.

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Hwang, Ji Young; Randall, Troy D; Silva-Sanchez, Aaron

2016-01-01

Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.

SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes.

NARCIS (Netherlands)

Diepen, van Janna A.; Hooiveld, Guido; Stienstra, Rinke; Deen, Peter M.

2017-01-01

Obesity induces macrophages to drive inflammation in adipose tissue, a crucial step towards the development of type 2 diabetes. The tricarboxylic acid (TCA) cycle intermediate succinate is released from cells under metabolic stress and has recently emerged as a metabolic signal induced by

The NALP3/Cryopyrin-Inflammasome Complex is Expressed in LPS-Induced Ocular Inflammation

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José F. González-Benítez

2008-01-01

Full Text Available In the inflammosome complex, NALP3 or NALP1 binds to ASC and activates caspase-1 which induces IL-1β. In murine LPS-induced ocular inflammation, the production of IL-1β is increased. We suggest that NALP3- or NALP1-inflammasome complex can be participating in the LPS-induced ocular inflammation. In this work, eye, brain, testis, heart, spleen, and lung were obtained from C3H/HeN mice treated with LPS for 3 to 48 hours, and the expression of NALP1b, NALP3, ASC, caspase-1, IL-1β, and IL-18 was determined. Infiltrated leukocytes producing IL-1β in the anterior chamber were found at 12-hour posttreatment. A high upregulated expression of NALP3, ASC, caspase-1, IL-1β, and IL-18 was found at the same time when infiltrated leukocytes were observed. NALP1b was not detected in the eye of treated mice. NALP3 was also overexpressed in heart and lung. These results suggest that NALP3-, but not NALP1-inflammosome complex, is participating in the murine LPS-induced ocular inflammation.

Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats.

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Cao, Zhengwang; Fang, Yiliang; Lu, Yonghui; Qian, Fenghua; Ma, Qinglong; He, Mingdi; Pi, Huifeng; Yu, Zhengping; Zhou, Zhou

2016-01-01

With recent advances in the manufacture and application of nickel oxide nanoparticles (NiONPs), concerns about their adverse effects on the respiratory system are increasing. However, the underlying cellular and molecular mechanisms of NiONP-induced pulmonary toxicity remain unclear. In this study, we focused on the impacts of NiONPs on pulmonary inflammation and investigated whether the NLRP3 inflammasome is involved in NiONP-induced pulmonary inflammation and injury. NiONP suspensions were administered by single intratracheal instillation to rats, and inflammatory responses were evaluated at 3 days, 7 days, or 28 days after treatment. NiONP exposure resulted in sustained pulmonary inflammation accompanied by inflammatory cell infiltration, alveolar proteinosis, and cytokine secretion. Expression of Nlrp3 was markedly upregulated by the NiONPs, which was accompanied by overexpression of the active form of caspase-1 (p20) and interleukin (IL)-1β secretion in vivo. NiONP-induced IL-1β secretion was partially prevented by co-treatment with a caspase-1 inhibitor in macrophages. Moreover, siRNA-mediated Nlrp3 knockdown completely attenuated NiONP-induced cytokine release and caspase-1 activity in macrophages in vitro. In addition, NiONP-induced NLRP3 inflammasome activation requires particle uptake and reactive oxygen species production. Collectively, our findings suggest that the NLRP3 inflammasome participates in NiONP-induced pulmonary inflammation and offer new strategies to combat the pulmonary toxicity induced by NiONPs.

Wear Behavior of Medium Carbon Steel with Biomimetic Surface Under Starved Lubricated Conditions

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Zhang, Zhihui; Shao, Feixian; Liang, Yunhong; Lin, Pengyu; Tong, Xin; Ren, Luquan

2017-07-01

Friction and wear under starved lubrication condition are both key life-related factors for mechanical performance of many structural parts. In this paper, different surface morphologies on medium carbon steel were fabricated using laser, inspired by the surface coupling effect of biological system. The friction and sliding wear behaviors of biomimetic specimens (characterized by convex and concave units on the specimen surface) were studied under starved lubrication condition. The stress distribution on different sliding surfaces under sliding friction was studied using finite element method. The results showed that the tribological performance of studied surfaces under starved lubrication condition depended not only on the surface morphology but also on the structure of biomimetic units below surface (subsurface structure). The friction coefficient of biomimetic surface was effectively reduced by the concave unit depth, while the refined microstructure with higher hardness led to the much better wear resistance. In addition to lubricant reserving and wear debris trapping effect derived from the surface concave morphology, it was believed that the well-formed subsurface structure of biomimetic units could carry much heavy loads against tribopair, which enhanced the function of surface topography and resulted in complementary lubrication in the wear contact area. The uniform stress distribution on the entire biomimetic surface also played an important role in stabilizing the friction coefficient and reducing the wear cracks.

Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

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Takeshi Tohyama

Full Text Available Lipopolysaccharide (LPS induces acute inflammation, activates sympathetic nerve activity (SNA and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP, examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis.Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg. We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection.In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.. In contrast, AP increased initially (until 75 min, then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP.LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and

Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

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Tohyama, Takeshi; Saku, Keita; Kawada, Toru; Kishi, Takuya; Yoshida, Keimei; Nishikawa, Takuya; Mannoji, Hiroshi; Kamada, Kazuhiro; Sunagawa, Kenji; Tsutsui, Hiroyuki

2018-01-01

Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed

Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

International Nuclear Information System (INIS)

Takai, Atsushi; Marusawa, Hiroyuki; Chiba, Tsutomu

2011-01-01

Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis

Transient infection of the zebrafish notochord with E. coli induces chronic inflammation.

Science.gov (United States)

Nguyen-Chi, Mai; Phan, Quang Tien; Gonzalez, Catherine; Dubremetz, Jean-François; Levraud, Jean-Pierre; Lutfalla, Georges

2014-07-01

Zebrafish embryos and larvae are now well-established models in which to study infectious diseases. Infections with non-pathogenic Gram-negative Escherichia coli induce a strong and reproducible inflammatory response. Here, we study the cellular response of zebrafish larvae when E. coli bacteria are injected into the notochord and describe the effects. First, we provide direct evidence that the notochord is a unique organ that is inaccessible to leukocytes (macrophages and neutrophils) during the early stages of inflammation. Second, we show that notochord infection induces a host response that is characterised by rapid clearance of the bacteria, strong leukocyte recruitment around the notochord and prolonged inflammation that lasts several days after bacteria clearance. During this inflammatory response, il1b is first expressed in macrophages and subsequently at high levels in neutrophils. Moreover, knock down of il1b alters the recruitment of neutrophils to the notochord, demonstrating the important role of this cytokine in the maintenance of inflammation in the notochord. Eventually, infection of the notochord induces severe defects of the notochord that correlate with neutrophil degranulation occurring around this tissue. This is the first in vivo evidence that neutrophils can degranulate in the absence of a direct encounter with a pathogen. Persistent inflammation, neutrophil infiltration and restructuring of the extracellular matrix are defects that resemble those seen in bone infection and in some chondropathies. As the notochord is a transient embryonic structure that is closely related to cartilage and bone and that contributes to vertebral column formation, we propose infection of the notochord in zebrafish larvae as a new model to study the cellular and molecular mechanisms underlying cartilage and bone inflammation. © 2014. Published by The Company of Biologists Ltd.

Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

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Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

2015-08-28

Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

Quantitative evaluation of apical extrusion of debris and irrigants using four rotary instrumentation systems: an in vitro study.

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Nagaveni, S Aspalli; Balakoti, K Reddy; Smita, Karan; Ratnakar, P; Satish, S V; Aravind, T

2013-11-01

The apical extrusion of infected debris may have the potential to disrupt the balance between microbial aggression and host defense, resulting in incidents of acute inflammation. During preparation, irrigants and debris, such as bacteria, dentin filings and necrotic tissue may be extruded into the periradicular region leading to periapical inflammation and postoperative flare ups. Using an instrumentation technique that minimizes apical extrusion would be beneficial to both the practitioner and patient. The purpose of the study was to evaluate the weight of debris and volume of irrigant extruded apically from extracted teeth in vitro after endodontic instrumentation using four different rotary root canal instrumentation systems. Four groups of each 20 extracted mandibular premolars were instrumented using one of the four systems: ProTaper Universal (Dentsply Maillefer, Ballaigues, Switzerland)), Hero-shaper (MicroMega, Besancon, France), RaCe (FKG Dentaire, La-Chaux-de-Fonds, Switzerland) and K3 (SybronEndo, West Collins, CA). Debris and irrigant extruded from the apical foramen during instrumentation were collected in preweighed test tubes. Volume of irrigant extruded was noted. The containers were stored in incubator at 70° for two days to evaporate the moisture. Weight of dry debris was noted. Data was analyzed using Kruskall-Wallis and Mann-Whitney U test at a significance of 0.001. The results indicated that all of the instrumentation systems tested caused measurable apical extrusion of debris and irrigants. Higher extrusion was observed with Protaper system which was statistically significant with Hero-Shaper, RaCe and K3 systems. There were no statistical differences between Hero-shaper, K3 and RaCe systems (p < 0.05). All instrumentation techniques apically extruded debris and irrigant. However, Hero-shaper, K3 and RaCe systems produced less extruded debris and irrigant than the Protaper system.

Dry sliding wear behaviour of Al-12Si-4Mg alloy with cerium addition

International Nuclear Information System (INIS)

Anasyida, A.S.; Daud, A.R.; Ghazali, M.J.

2010-01-01

The purpose of this work is to understand the effect of cerium addition on wear resistance behaviour of as-cast alloys. Al-12Si-4 Mg alloys with 1-5 wt% cerium addition were prepared using the casting technique. A sliding wear test was carried out under applied loads of 10 N, 30 N and 50 N at a fixed sliding speed of 1 m/s using a pin-on-disc configuration. The wear test was conducted in dry conditions at room temperature of ∼25 o C. Detailed analysis of the microstructure, worn surface, collected debris and microhardness was undertaken in order to investigate the differences between the as-cast alloys with different levels of cerium addition. The addition of 1-5 wt% cerium was found to lead to the precipitation of intermetallic phases (Al-Ce), resulting a needle-like structures. Increasing cerium content up to 2 wt% improved both wear resistance and microhardness of as-cast alloys. Addition of more than 2 wt% cerium, however, led to a decrease in microhardness, resulting in lower wear resistance of the alloys. Moderate wear was observed at all loads, with specific wear rates (K') ranging from 6.82 x 10 -5 with 2 wt% Ce at applied load of 50 N to 21.48 x 10 -5 mm 3 /N m without added Ce at an applied load of 10 N. Based on K' ranges, the as-cast alloys exhibited moderate wear regimes, and the mechanism of wear is a combination of abrasion and adhesion. Alloy containing 2 wt% Ce, with the highest hardness and lowest K' value, showed the greatest wear resistance.

Shikonin ameliorates isoproterenol (ISO)-induced myocardial damage through suppressing fibrosis, inflammation, apoptosis and ER stress.

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Yang, Jun; Wang, Zhao; Chen, Dong-Lin

2017-09-01

Shikonin, isolated from the roots of herbal plant Lithospermum erythrorhizon, is a naphthoquinone. It has been reported to exert beneficial anti-inflammatory effects and anti-oxidant properties in various diseases. Isoproterenol (ISO) has been widely used to establish cardiac injury in vivo and in vitro. However, shikonin function in ISO-induced cardiac injury remains uncertain. In our study, we attempted to investigate the efficiency and possible molecular mechanism of shikonin in cardiac injury treatment induced by ISO. In vivo, C57BL6 mice were subcutaneously injected with 5mg/kg ISO to induce heart failure. And mice were given a gavage of shikonin (2 or 4mg/kg/d, for four weeks). Cardiac function, fibrosis indices, inflammation response, apoptosis and endoplasmic reticulum (ER) stress were calculated. Pathological alterations, fibrosis-, inflammation-, apoptosis- and ER stress-related molecules were examined. In ISO-induced cardiac injury, shikonin significantly ameliorated heart function, decreased myocardial fibrosis, suppressed inflammation, attenuated apoptosis and ER stress through impeding collagen accumulation, Toll like receptor 4/nuclear transcription factor κB (TLR4/NF-κB), Caspase-3 and glucose-regulated protein 78 (GRP78) signaling pathways activity, relieving heart failure in vivo. Also, in vitro, shikonin attenuated ISO-induced cardiac muscle cells by reducing fibrosis, inflammation, apoptosis and ER stress. Our findings indicated that shikonin treatment attenuated ISO-induced heart injury, providing an effective therapeutic strategy for heart failure treatment for future. Copyright © 2017. Published by Elsevier Masson SAS.

Wear rate quantifying in real-time using the charged particle surface activation

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Alexandreanu, B.; Popa-Simil, L.; Voiculescu, D.; Racolta, P. M.

1997-02-01

Surface activation, commonly known as Thin Layer Activation (TLA), is currently employed in over 30 accelerator laboratories around the world for wear and/or corrosion monitoring in industrial plants [1-6]. TLA was primarily designed and developed to meet requirements of potential industrial partners, in order to transfer this technique from research to industry. The method consists of accelerated ion bombardment of a surface of interest, e.g., a machine part subjected to wear. Loss of material owing to wear, erosive corrosion or abrasion is characterized by monitoring the resultant changes in radioactivity. In principle, depending upon the case at hand, one may choose to measure either the remnant activity of the component of interest or to monitor the activity of the debris. For applications of the second type, especially when a lubricating agent is involved, dedicated installations have been constructed and adapted to an engine or a tribological testing stand in order to assure oil circulation around an externally placed detection gauge. This way, the wear particles suspended in the lubricant can be detected and the material loss rates quantified in real time. Moreover, in specific cases, such as the one presented in this paper, remnant activity measurements prove to be useful tools for complementary results. This paper provides a detailed presentation of such a case: in situ resistance-to-wear testing of two types of piston rings.

Wear performance of garnet aluminium composites at high contact pressure

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Sharma, Anju; Arora, Rama; Kumar, Suresh; Singh, Gurmel; Pandey, O. P.

2016-05-01

To satisfy the needs of the engineering sector, researchers and material scientists in this area adopted the development of composites with tailor made properties to enhance efficiency and cost savings in the manufacturing sector. The technology of the mineral industry is shaping the supply and demand of minerals derived materials. The composites are best classified as high performance materials have high strength-to-weight ratios, and require controlled manufacturing environments for optimum performance. Natural mineral garnet was used as the reinforcement of composite because of satisfactory mechanical properties as well as an attractive ecological alternative to others ceramics. For this purpose, samples have been prepared with different sizesof the garnet reinforcement using the mechanical stirring method to achieve the homogeneously dispersed strengthening phase. A systematic study of the effect of high contact pressure on the sliding wear behaviour of garnet reinforced LM13 alloy composites is presented in this paper. The SEM analysis of the worn samples and debris reveals the clues about the wear mechanism. The drastic improvement in the wear resistance of the composites at high contact pressure shows the high potential of the material to be used in engineering applications.

Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

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Halliday, Gary M. [Dermatology Research Laboratories, Division of Medicine, Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital at the University of Sydney, Sydney, NSW (Australia)]. E-mail: garyh@med.usyd.edu.au

2005-04-01

Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans.

Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

International Nuclear Information System (INIS)

Halliday, Gary M.

2005-01-01

Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans

A real two-phase submarine debris flow and tsunami

International Nuclear Information System (INIS)

Pudasaini, Shiva P.; Miller, Stephen A.

2012-01-01

The general two-phase debris flow model proposed by Pudasaini is employed to study subaerial and submarine debris flows, and the tsunami generated by the debris impact at lakes and oceans. The model, which includes three fundamentally new and dominant physical aspects such as enhanced viscous stress, virtual mass, and generalized drag (in addition to buoyancy), constitutes the most generalized two-phase flow model to date. The advantage of this two-phase debris flow model over classical single-phase, or quasi-two-phase models, is that the initial mass can be divided into several parts by appropriately considering the solid volume fraction. These parts include a dry (landslide or rock slide), a fluid (water or muddy water; e.g., dams, rivers), and a general debris mixture material as needed in real flow simulations. This innovative formulation provides an opportunity, within a single framework, to simultaneously simulate the sliding debris (or landslide), the water lake or ocean, the debris impact at the lake or ocean, the tsunami generation and propagation, the mixing and separation between the solid and fluid phases, and the sediment transport and deposition process in the bathymetric surface. Applications of this model include (a) sediment transport on hill slopes, river streams, hydraulic channels (e.g., hydropower dams and plants); lakes, fjords, coastal lines, and aquatic ecology; and (b) submarine debris impact and the rupture of fiber optic, submarine cables and pipelines along the ocean floor, and damage to offshore drilling platforms. Numerical simulations reveal that the dynamics of debris impact induced tsunamis in mountain lakes or oceans are fundamentally different than the tsunami generated by pure rock avalanches and landslides. The analysis includes the generation, amplification and propagation of super tsunami waves and run-ups along coastlines, debris slide and deposition at the bottom floor, and debris shock waves. It is observed that the

A real two-phase submarine debris flow and tsunami

Energy Technology Data Exchange (ETDEWEB)

Pudasaini, Shiva P.; Miller, Stephen A. [Department of Geodynamics and Geophysics, Steinmann Institute, University of Bonn Nussallee 8, D-53115, Bonn (Germany)

2012-09-26

The general two-phase debris flow model proposed by Pudasaini is employed to study subaerial and submarine debris flows, and the tsunami generated by the debris impact at lakes and oceans. The model, which includes three fundamentally new and dominant physical aspects such as enhanced viscous stress, virtual mass, and generalized drag (in addition to buoyancy), constitutes the most generalized two-phase flow model to date. The advantage of this two-phase debris flow model over classical single-phase, or quasi-two-phase models, is that the initial mass can be divided into several parts by appropriately considering the solid volume fraction. These parts include a dry (landslide or rock slide), a fluid (water or muddy water; e.g., dams, rivers), and a general debris mixture material as needed in real flow simulations. This innovative formulation provides an opportunity, within a single framework, to simultaneously simulate the sliding debris (or landslide), the water lake or ocean, the debris impact at the lake or ocean, the tsunami generation and propagation, the mixing and separation between the solid and fluid phases, and the sediment transport and deposition process in the bathymetric surface. Applications of this model include (a) sediment transport on hill slopes, river streams, hydraulic channels (e.g., hydropower dams and plants); lakes, fjords, coastal lines, and aquatic ecology; and (b) submarine debris impact and the rupture of fiber optic, submarine cables and pipelines along the ocean floor, and damage to offshore drilling platforms. Numerical simulations reveal that the dynamics of debris impact induced tsunamis in mountain lakes or oceans are fundamentally different than the tsunami generated by pure rock avalanches and landslides. The analysis includes the generation, amplification and propagation of super tsunami waves and run-ups along coastlines, debris slide and deposition at the bottom floor, and debris shock waves. It is observed that the

Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats.

Science.gov (United States)

Wang, T; Liu, Y; Chen, L; Wang, X; Hu, X-R; Feng, Y-L; Liu, D-S; Xu, D; Duan, Y-P; Lin, J; Ou, X-M; Wen, F-Q

2009-05-01

Airway inflammation with mucus overproduction is a distinguishing pathophysiological feature of many chronic respiratory diseases. Phosphodiesterase (PDE) inhibitors have shown anti-inflammatory properties. In the present study, the effect of sildenafil, a potent inhibitor of PDE5 that selectively degrades cyclic guanosine 3',5'-monophosphate (cGMP), on acrolein-induced inflammation and mucus production in rat airways was examined. Rats were exposed to acrolein for 14 and 28 days. Sildenafil or distilled saline was administered intragastrically prior to acrolein exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell count and the detection of pro-inflammatory cytokine levels. Lung tissue was examined for cGMP content, nitric oxide (NO)-metabolite levels, histopathological lesion scores, goblet cell metaplasia and mucin production. The results suggested that sildenafil pretreatment reversed the significant decline of cGMP content in rat lungs induced by acrolein exposure, and suppressed the increase of lung NO metabolites, the BALF leukocyte influx and pro-inflammatory cytokine release. Moreover, sildenafil pretreatment reduced acrolein-induced Muc5ac mucin synthesis at both mRNA and protein levels, and attenuated airway inflammation, as well as epithelial hyperplasia and metaplasia. In conclusion, sildenafil could attenuate airway inflammation and mucus production in the rat model, possibly through the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, and, thus, might have a therapeutic potential for chronic airway diseases.

Space Transportation System Liftoff Debris Mitigation Process Overview

Science.gov (United States)

Mitchell, Michael; Riley, Christopher

2011-01-01

Liftoff debris is a top risk to the Space Shuttle Vehicle. To manage the Liftoff debris risk, the Space Shuttle Program created a team with in the Propulsion Systems Engineering & Integration Office. The Shutt le Liftoff Debris Team harnesses the Systems Engineering process to i dentify, assess, mitigate, and communicate the Liftoff debris risk. T he Liftoff Debris Team leverages off the technical knowledge and expe rtise of engineering groups across multiple NASA centers to integrate total system solutions. These solutions connect the hardware and ana lyses to identify and characterize debris sources and zones contribut ing to the Liftoff debris risk. The solutions incorporate analyses sp anning: the definition and modeling of natural and induced environmen ts; material characterizations; statistical trending analyses, imager y based trajectory analyses; debris transport analyses, and risk asse ssments. The verification and validation of these analyses are bound by conservative assumptions and anchored by testing and flight data. The Liftoff debris risk mitigation is managed through vigilant collab orative work between the Liftoff Debris Team and Launch Pad Operation s personnel and through the management of requirements, interfaces, r isk documentation, configurations, and technical data. Furthermore, o n day of launch, decision analysis is used to apply the wealth of ana lyses to case specific identified risks. This presentation describes how the Liftoff Debris Team applies Systems Engineering in their proce sses to mitigate risk and improve the safety of the Space Shuttle Veh icle.

Anti-Inflammatory Effects of Licorice and Roasted Licorice Extracts on TPA-Induced Acute Inflammation and Collagen-Induced Arthritis in Mice

Directory of Open Access Journals (Sweden)

Ki Rim Kim

2010-01-01

Full Text Available The anti-inflammatory activity of licorice (LE and roated licorice (rLE extracts determined in the murine phorbol ester-induced acute inflammation model and collagen-induced arthritis (CIA model of human rheumatoid arthritis. rLE possessed greater activity than LE in inhibiting phorbol ester-induced ear edema. Oral administration of LE or rLE reduced clinical arthritis score, paw swelling, and histopathological changes in a murine CIA. LE and rLE decreased the levels of proinflammatory cytokines in serum and matrix metalloproteinase-3 expression in the joints. Cell proliferation and cytokine secretion in response to type II collagen or lipopolysaccharide stimulation were suppressed in spleen cells from LE or rLE-treated CIA mice. Furthermore, LE and rLE treatment prevented oxidative damages in liver and kidney tissues of CIA mice. Taken together, LE and rLE have benefits in protecting against both acute inflammation and chronic inflammatory conditions including rheumatoid arthritis. rLE may inhibit the acute inflammation more potently than LE.

Wear Behavior and Microstructure of Mg-Sn Alloy Processed by Equal Channel Angular Extrusion.

Science.gov (United States)

Chen, Jung-Hsuan; Shen, Yen-Chen; Chao, Chuen-Guang; Liu, Tzeng-Feng

2017-11-16

Mg-5wt.% Sn alloy is often used in portable electronic devices and automobiles. In this study, mechanical properties of Mg-5wt.% Sn alloy processed by Equal Channel Angular Extrusion (ECAE) were characterized. More precisely, its hardness and wear behavior were measured using Vickers hardness test and a pin-on-disc wear test. The microstructures of ECAE-processed Mg-Sn alloys were investigated by scanning electron microscope and X-ray diffraction. ECAE process refined the grain sizes of the Mg-Sn alloy from 117.6 μm (as-cast) to 88.0 μm (one pass), 49.5 μm (two passes) and 24.4 μm (four passes), respectively. Meanwhile, the hardness of the alloy improved significantly. The maximum wear resistance achieved in the present work was around 73.77 m/mm³, which was obtained from the Mg-Sn alloy treated with a one-pass ECAE process with a grain size of 88.0 μm. The wear resistance improvement was caused by the grain size refinement and the precipitate of the second phase, Mg₂Sn against the oxidation of the processed alloy. The as-cast Mg-Sn alloy with the larger grain size, i.e., 117.6 μm, underwent wear mechanisms, mainly adhesive wear and abrasive wear. In ECAE-processed Mg-Sn alloy, high internal energy occurred due to the high dislocation density and the stress field produced by the plastic deformation, which led to an increased oxidation rate of the processed alloy during sliding. Therefore, the oxidative wear and a three-body abrasive wear in which the oxide debris acted as the three-body abrasive components became the dominant factors in the wear behavior, and as a result, reduced the wear resistance in the multi-pass ECAE-processed alloy.

Study of Surface Wear and Damage Induced by Dry Sliding of Tempered AISI 4140 Steel against Hardened AISI 1055 Steel

Directory of Open Access Journals (Sweden)

A. Elhadi

2016-12-01

Full Text Available In industry, the sliding mechanical systems are subject to friction and wear phenomena. These phenomena can be the origin of a reduction of the efficiency of the mechanical system even to be responsible for its incapacity. Generally, the materials of the parts which are moving relative (tribological couple of these systems are low alloy steels and carbon steels, thanks to their good mechanical and tribological properties. The present work aimed to study, the surface wear and damage induced by dry sliding of hard carbon steel AISI 1055 (disc against tempered low alloy steel AISI 4140 (pin with different hardness and applied loads was investigated. The results revealed that the interaction between the applied load and pin hardness result in complex thermo-mechanical behaviour of the worn surfaces. When a lower hardness pin is used, the main wear mechanisms observed on the discs were abrasion, adhesion, and oxidation. When a higher hardness pin is used, the wear of the discs is governed by delamination, oxidation, and plastic deformation. In particular, third-body wear occurs at high applied load resulting in higher wear rate of high hardness pins compared to low hardness pins.

Autogenic dynamics of debris-flow fans

Science.gov (United States)

van den Berg, Wilco; de Haas, Tjalling; Braat, Lisanne; Kleinhans, Maarten

2015-04-01

Alluvial fans develop their semi-conical shape by cyclic avulsion of their geomorphologically active sector from a fixed fan apex. These cyclic avulsions have been attributed to both allogenic and autogenic forcings and processes. Autogenic dynamics have been extensively studied on fluvial fans through physical scale experiments, and are governed by cyclic alternations of aggradation by unconfined sheet flow, fanhead incision leading to channelized flow, channel backfilling and avulsion. On debris-flow fans, however, autogenic dynamics have not yet been directly observed. We experimentally created debris-flow fans under constant extrinsic forcings, and show that autogenic dynamics are a fundamental intrinsic process on debris-flow fans. We found that autogenic cycles on debris-flow fans are driven by sequences of backfilling, avulsion and channelization, similar to the cycles on fluvial fans. However, the processes that govern these sequences are unique for debris-flow fans, and differ fundamentally from the processes that govern autogenic dynamics on fluvial fans. We experimentally observed that backfilling commenced after the debris flows reached their maximum possible extent. The next debris flows then progressively became shorter, driven by feedbacks on fan morphology and flow-dynamics. The progressively decreasing debris-flow length caused in-channel sedimentation, which led to increasing channel overflow and wider debris flows. This reduced the impulse of the liquefied flow body to the flow front, which then further reduced flow velocity and runout length, and induced further in-channel sedimentation. This commenced a positive feedback wherein debris flows became increasingly short and wide, until the channel was completely filled and the apex cross-profile was plano-convex. At this point, there was no preferential transport direction by channelization, and the debris flows progressively avulsed towards the steepest, preferential, flow path. Simultaneously

Tooth wear and wear investigations in dentistry.

Science.gov (United States)

Lee, A; He, L H; Lyons, K; Swain, M V

2012-03-01

Tooth wear has been recognised as a major problem in dentistry. Epidemiological studies have reported an increasing prevalence of tooth wear and general dental practitioners see a greater number of patients seeking treatment with worn dentition. Although the dental literature contains numerous publications related to management and rehabilitation of tooth wear of varying aetiologies, our understanding of the aetiology and pathogenesis of tooth wear is still limited. The wear behaviour of dental biomaterials has also been extensively researched to improve our understanding of the underlying mechanisms and for the development of restorative materials with good wear resistance. The complex nature of tooth wear indicates challenges for conducting in vitro and in vivo wear investigations and a clear correlation between in vitro and in vivo data has not been established. The objective was to critically review the peer reviewed English-language literature pertaining to prevalence and aetiology of tooth wear and wear investigations in dentistry identified through a Medline search engine combined with hand-searching of the relevant literature, covering the period between 1960 and 2011. © 2011 Blackwell Publishing Ltd.

Inflammation-induced preterm lung maturation: lessons from animal experimentation.

Science.gov (United States)

Moss, Timothy J M; Westover, Alana J

2017-06-01

Intrauterine inflammation, or chorioamnionitis, is a major contributor to preterm birth. Prematurity per se is associated with considerable morbidity and mortality resulting from lung immaturity but exposure to chorioamnionitis reduces the risk of neonatal respiratory distress syndrome (RDS) in preterm infants. Animal experiments have identified that an increase in pulmonary surfactant production by the preterm lungs likely underlies this decreased risk of RDS in infants exposed to chorioamnionitis. Further animal experimentation has shown that infectious or inflammatory agents in amniotic fluid exert their effects on lung development by direct effects within the developing respiratory tract, and probably not by systemic pathways. Differences in the effects of intrauterine inflammation and glucocorticoids demonstrate that canonical glucocorticoid-mediated lung maturation is not responsible for inflammation-induced changes in lung development. Animal experimentation is identifying alternative lung maturational pathways, and transgenic animals and cell culture techniques will allow identification of novel mechanisms of lung maturation that may lead to new treatments for the prevention of RDS. Copyright © 2016. Published by Elsevier Ltd.

Fractionation and characterization of particles simulating wear of total joint replacement (TJR) following ASTM standards.

Science.gov (United States)

Saha, Subrata; Musib, Mrinal

2011-01-01

Reactions of bone cells to orthopedic wear debris produced by the articulating motion of total joint replacements (TJRs) are largely responsible for the long-term failure of such replacements. Metal and polyethylene (PE) wear particles isolated from fluids from total joint simulators, as well as particles that are fabricated by other methods, are widely used to study such in vitro cellular response. Prior investigations have revealed that cellular response to wear debris depends on the size, shape, and dose of the particles. Hence, to have a better understanding of the wear-mediated osteolytic process it is important that these particles are well characterized and clinically relevant, both qualitatively, and quantitatively. In this study we have fractionated both ultra-high molecular weight polyethylene (UHMWPE) and Ti particles, into micron (1.0-10.0 μm), submicron (0.2-1.0 μm), and nanoparticle (0.01-0.2 μm) fractions, and characterized them based on the following size-shape descriptors as put forth in ASTM F1877: i) equivalent circle diameter (ECD), ii) aspect ratio (AR), iii) elongation (E), iv) roundness (R), and v) form factor (FF). The mean (± SD) ECDs (in μm) for micron, submicron, and nanoparticles of UHMWPE were 1.652 ± 0.553, 0.270 ± 0.180, and 0.061 ± 0.035, respectively, and for Ti were 1.894 ± 0.667, 0.278 ± 0.180, and 0.055 ± 0.029, respectively. The values for other descriptors were similar (no statistically significant difference). The nanofraction particles were found to be more sphere-like (higher R and FF values, and lower E and AR values) as compared to larger particles. Future experiments will involve use of these well characterized particles for in vitro studies.

Intervention effect and dose-dependent response of tanreqing injection on airway inflammation in lipopolysaccharide-induced rats.

Science.gov (United States)

Dong, Shoujin; Zhong, Yunqing; Yang, Kun; Xiong, Xiaoling; Mao, Bing

2013-08-01

To assess the effect of Tanreqing injection on airway inflammation in rats. A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-13, cytokine-induced neutrophil chemoat-tractant-1, and tumor necrosis factor-alpha were measured using enzyme linked immunosorbent assay. The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China); Qiao, Juan, E-mail: qjuan@tsinghua.edu.cn [Department of Chemistry, Tsinghua University, Beijing 100084 (China); Lu, Yun, E-mail: luyun@tsinghua.edu.cn [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China)

2016-02-13

Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

International Nuclear Information System (INIS)

Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani; Qiao, Juan; Lu, Yun

2016-01-01

Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

12-oxo-phytodienoic acid, a plant-derived oxylipin, attenuates lipopolysaccharide-induced inflammation in microglia

Energy Technology Data Exchange (ETDEWEB)

Taki-Nakano, Nozomi [Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan); Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505 (Japan); Kotera, Jun [Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505 (Japan); Ohta, Hiroyuki, E-mail: ohta.h.ab@m.titech.ac.jp [Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan); School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan)

2016-05-13

Jasmonates are plant lipid–derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)–induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDA suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling. -- Highlights: •OPDA attenuates LPS-induced inflammatory cytokines such as IL-6 and TNF-α. •OPDA reduces LPS-induced iNOS expression and NO production. •OPDA suppresses NF-κB and p38 pathways and activates SOCS-1 signaling.

12-oxo-phytodienoic acid, a plant-derived oxylipin, attenuates lipopolysaccharide-induced inflammation in microglia

International Nuclear Information System (INIS)

Taki-Nakano, Nozomi; Kotera, Jun; Ohta, Hiroyuki

2016-01-01

Jasmonates are plant lipid–derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)–induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDA suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling. -- Highlights: •OPDA attenuates LPS-induced inflammatory cytokines such as IL-6 and TNF-α. •OPDA reduces LPS-induced iNOS expression and NO production. •OPDA suppresses NF-κB and p38 pathways and activates SOCS-1 signaling.

Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids.

Science.gov (United States)

Choi, Sun Ju; Kim, Francis; Schwartz, Michael W; Wisse, Brent E

2010-06-01

Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity. Since in vitro exposure to saturated fatty acids causes inflammation and insulin resistance in many cultured cell types, we determined how cultured hypothalamic neurons respond to this stimulus. Two murine hypothalamic neuronal cell cultures, N43/5 and GT1-7, were exposed to escalating concentrations of saturated fatty acids for up to 24 h. Harvested cells were evaluated for activation of inflammation by gene expression and protein content. Insulin-treated cells were evaluated for induction of markers of insulin receptor signaling (p-IRS, p-Akt). In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFalpha, as judged by induction of IkappaBalpha (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IkappaBalpha protein, and TNFalpha pretreatment reduced insulin-mediated p-Akt activation by 30% (P fatty acid (100, 250, or 500 microM for neurons, whereas they did in control muscle and endothelial cell lines. Despite the lack of evidence of inflammatory signaling, saturated fatty acid exposure in cultured hypothalamic neurons causes endoplasmic reticulum stress, induces mitogen-activated protein kinase, and causes apoptotic cell death with prolonged exposure. We conclude that saturated fatty acid exposure does not induce inflammatory signaling or insulin resistance in cultured hypothalamic neurons. Therefore, hypothalamic neuronal inflammation in the setting of DIO may involve an indirect mechanism mediated by saturated fatty acids on nonneuronal cells.

Grain dust-induced lung inflammation is reduced by Rhodobacter sphaeroides diphosphoryl lipid A.

Science.gov (United States)

Jagielo, P J; Quinn, T J; Qureshi, N; Schwartz, D A

1998-01-01

To further determine the importance of endotoxin in grain dust-induced inflammation of the lower respiratory tract, we evaluated the efficacy of pentaacylated diphosphoryl lipid A derived from the lipopolysaccharide of Rhodobacter sphaeroides (RsDPLA) as a partial agonist of grain dust-induced airway inflammation. RsDPLA is a relatively inactive compound compared with lipid A derived from Escherichia coli (LPS) and has been demonstrated to act as a partial agonist of LPS-induced inflammation. To assess the potential stimulatory effect of RsDPLA in relation to LPS, we incubated THP-1 cells with RsDPLA (0.001-100 micrograms/ml), LPS (0.02 microgram endotoxin activity/ml), or corn dust extract (CDE; 0.02 microgram endotoxin activity/ml). Incubation with RsDPLA revealed a tumor necrosis factor (TNF)-alpha stimulatory effect at 100 micrograms/ml. In contrast, incubation with LPS or CDE resulted in TNF-alpha release at 0.02 microgram/ml. Pretreatment of THP-1 cells with varying concentrations of RsDPLA before incubation with LPS or CDE (0.02 microgram endotoxin activity/ml) resulted in a dose-dependent reduction in the LPS- or CDE-induced release of TNF-alpha with concentrations of RsDPLA of up to 10 micrograms/ml but not at 100 micrograms/ml. To further understand the role of endotoxin in grain dust-induced airway inflammation, we utilized the unique LPS inhibitory property of RsDPLA to determine the inflammatory response to inhaled CDE in mice in the presence of RsDPLA. Ten micrograms of RsDPLA intratracheally did not cause a significant inflammatory response compared with intratracheal saline. However, pretreatment of mice with 10 micrograms of RsDPLA intratracheally before exposure to CDE (5.4 and 0.2 micrograms/m3) or LPS (7.2 and 0.28 micrograms/m3) resulted in significant reductions in the lung lavage concentrations of total cells, neutrophils, and specific proinflammatory cytokines compared with mice pretreated with sterile saline. These results confirm the LPS

Exercise protects against high-fat diet-induced hypothalamic inflammation.

Science.gov (United States)

Yi, Chun-Xia; Al-Massadi, Omar; Donelan, Elizabeth; Lehti, Maarit; Weber, Jon; Ress, Chandler; Trivedi, Chitrang; Müller, Timo D; Woods, Stephen C; Hofmann, Susanna M

2012-06-25

Hypothalamic inflammation is a potentially important process in the pathogenesis of high-fat diet-induced metabolic disorders that has recently received significant attention. Microglia are macrophage-like cells of the central nervous system which are activated by pro-inflammatory signals causing local production of specific interleukins and cytokines, and these in turn may further promote systemic metabolic disease. Whether or how this microglial activation can be averted or reversed is unknown. Since running exercise improves systemic metabolic health and has been found to promote neuronal survival as well as the recovery of brain functions after injury, we hypothesized that regular treadmill running may blunt the effect of western diet on hypothalamic inflammation. Using low-density lipoprotein receptor deficient (l dlr-/-) mice to better reflect human lipid metabolism, we first confirmed that microglial activation in the hypothalamus is severely increased upon exposure to a high-fat, or "western", diet. Moderate, but regular, treadmill running exercise markedly decreased hypothalamic inflammation in these mice. Furthermore, the observed decline in microglial activation was associated with an improvement of glucose tolerance. Our findings support the hypothesis that hypothalamic inflammation can be reversed by exercise and suggest that interventions to avert or reverse neuronal damage may offer relevant potential in obesity treatment and prevention. Copyright © 2012 Elsevier Inc. All rights reserved.

On-line and precise measurement of iron wear using thin layer activation reactions by proton beam

International Nuclear Information System (INIS)

Kosako, Toshiso; Nishimura, Kazuo.

1990-01-01

For the purpose of the on-line measurement of iron wear, thin layer activation (TLA) method or surface layer activation (SLA) method has been carried out since early 1970s. This method uses the irradiation of charged particle beam like protons from an accelerator onto a metal surface to produce a thin activated layer of several tens μm. The wear of this activated layer is measured by nondestructive on-line method with a radiation detector. There are two methods of the measurement. One is the activity loss measurement on the surface, and the other is the activity measurement of the metal debris collected in a filter. The former method is considered here. The purpose it to measure the wear of engine cam noses to help the development of good engine oil. Proton beam irradiation with a tandem van de Graaff accelerator, wear calibration using a gamma ray spectrometer, on-line wear measurement of cam noses of car engines by TLA method and so on are reported. The 7.00 MeV proton beam from a van de Graaff accelerator was used for activation, and Co-56, Co-57 and Co-58 were obtained in thin layers. (K.I.)

Nox1 oxidase suppresses influenza a virus-induced lung inflammation and oxidative stress.

Directory of Open Access Journals (Sweden)

Stavros Selemidis

Full Text Available Influenza A virus infection is an ongoing clinical problem and thus, there is an urgent need to understand the mechanisms that regulate the lung inflammation in order to unravel novel generic pharmacological strategies. Evidence indicates that the Nox2-containing NADPH oxidase enzyme promotes influenza A virus-induced lung oxidative stress, inflammation and dysfunction via ROS generation. In addition, lung epithelial and endothelial cells express the Nox1 isoform of NADPH oxidase, placing this enzyme at key sites to regulate influenza A virus-induced lung inflammation. The aim of this study was to investigate whether Nox1 oxidase regulates the inflammatory response and the oxidative stress to influenza infection in vivo in mice. Male WT and Nox1-deficient (Nox1(-/y mice were infected with the moderately pathogenic HkX-31 (H3N2, 1×10(4 PFU influenza A virus for analysis of bodyweight, airways inflammation, oxidative stress, viral titre, lung histopathology, and cytokine/chemokine expression at 3 and 7 days post infection. HkX-31 virus infection of Nox1(-/y mice resulted in significantly greater: loss of bodyweight (Day 3; BALF neutrophilia, peri-bronchial, peri-vascular and alveolar inflammation; Nox2-dependent inflammatory cell ROS production and peri-bronchial, epithelial and endothelial oxidative stress. The expression of pro-inflammatory cytokines including CCL2, CCL3, CXCL2, IL-1β, IL-6, GM-CSF and TNF-α was higher in Nox1(-/y lungs compared to WT mice at Day 3, however, the expression of CCL2, CCL3, CXCL2, IFN-γ and the anti-inflammatory cytokine IL-10 were lower in lungs of Nox1(-/y mice vs. WT mice at Day 7. Lung viral titre, and airways infiltration of active CD8(+ and CD4(+ T lymphocytes, and of Tregs were similar between WT and Nox1(-/y mice. In conclusion, Nox1 oxidase suppresses influenza A virus induced lung inflammation and oxidative stress in mice particularly at the early phases of the infection. Nox1 and Nox2 oxidases appear

Teuvincenone F Suppresses LPS-Induced Inflammation and NLRP3 Inflammasome Activation by Attenuating NEMO Ubiquitination

OpenAIRE

Xibao Zhao; Xibao Zhao; Debing Pu; Debing Pu; Zizhao Zhao; Huihui Zhu; Hongrui Li; Hongrui Li; Yaping Shen; Xingjie Zhang; Ruihan Zhang; Jianzhong Shen; Weilie Xiao; Weilie Xiao; Weilin Chen

2017-01-01

Inflammation causes many diseases that are serious threats to human health. However, the molecular mechanisms underlying regulation of inflammation and inflammasome activation are not fully understood which has delayed the discovery of new anti-inflammatory drugs of urgent clinic need. Here, we found that the natural compound Teuvincenone F, which was isolated and purified from the stems and leaves of Premna szemaoensis, could significantly inhibit lipopolysaccharide (LPS)–induced pro-inflamm...

Teuvincenone F Suppresses LPS-Induced Inflammation and NLRP3 Inflammasome Activation by Attenuating NEMO Ubiquitination

OpenAIRE

Zhao, Xibao; Pu, Debing; Zhao, Zizhao; Zhu, Huihui; Li, Hongrui; Shen, Yaping; Zhang, Xingjie; Zhang, Ruihan; Shen, Jianzhong; Xiao, Weilie; Chen, Weilin

2017-01-01

Inflammation causes many diseases that are serious threats to human health. However, the molecular mechanisms underlying regulation of inflammation and inflammasome activation are not fully understood which has delayed the discovery of new anti-inflammatory drugs of urgent clinic need. Here, we found that the natural compound Teuvincenone F, which was isolated and purified from the stems and leaves of Premna szemaoensis, could significantly inhibit lipopolysaccharide (LPS)?induced pro-inflamm...

Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice.

Science.gov (United States)

Oostwoud, L C; Gunasinghe, P; Seow, H J; Ye, J M; Selemidis, S; Bozinovski, S; Vlahos, R

2016-02-15

Influenza A virus (IAV) infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Oxidative stress is increased in COPD, IAV-induced lung inflammation and AECOPD. Therefore, we investigated whether targeting oxidative stress with the Nox2 oxidase inhibitors and ROS scavengers, apocynin and ebselen could ameliorate lung inflammation in a mouse model of AECOPD. Male BALB/c mice were exposed to cigarette smoke (CS) generated from 9 cigarettes per day for 4 days. On day 5, mice were infected with 1 × 10(4.5) PFUs of the IAV Mem71 (H3N1). BALF inflammation, viral titers, superoxide production and whole lung cytokine, chemokine and protease mRNA expression were assessed 3 and 7 days post infection. IAV infection resulted in a greater increase in BALF inflammation in mice that had been exposed to CS compared to non-smoking mice. This increase in BALF inflammation in CS-exposed mice caused by IAV infection was associated with elevated gene expression of pro-inflammatory cytokines, chemokines and proteases, compared to CS alone mice. Apocynin and ebselen significantly reduced the exacerbated BALF inflammation and pro-inflammatory cytokine, chemokine and protease expression caused by IAV infection in CS mice. Targeting oxidative stress using apocynin and ebselen reduces IAV-induced lung inflammation in CS-exposed mice and may be therapeutically exploited to alleviate AECOPD.

Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure.

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Cristiane Miranda da Silva

Full Text Available Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA, an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1% or vehicle (distillated water during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure. Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant.

Schisantherin A suppresses osteoclast formation and wear particle-induced osteolysis via modulating RANKL signaling pathways

Energy Technology Data Exchange (ETDEWEB)

He, Yi; Zhang, Qing; Shen, Yi; Chen, Xia; Zhou, Feng; Peng, Dan, E-mail: xyeypd@163.com

2014-07-04

Highlights: • Schisantherin A suppresses osteoclasts formation and function in vitro. • Schisantherin A impairs RANKL signaling pathway. • Schisantherin A suppresses osteolysis in vivo. • Schisantherin A may be used for treating osteoclast related diseases. - Abstract: Receptor activator of NF-κB ligand (RANKL) plays critical role in osteoclastogenesis. Targeting RANKL signaling pathways has been a promising strategy for treating osteoclast related bone diseases such as osteoporosis and aseptic prosthetic loosening. Schisantherin A (SA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent, but its effect on osteoclasts has been hitherto unknown. In the present study, SA was found to inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, SA inhibited OSCAR, cathepsin K and TRAP in a dose dependent manner. Further signal transduction studies revealed that SA down-regulate RANKL-induced nuclear factor-kappaB (NF-κB) signaling activation by suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the NF-κB transcriptional activity. Moreover, SA also decreased the RANKL-induced MAPKs signaling pathway, including JNK and ERK1/2 posphorylation while had no obvious effects on p38 activation. Finally, SA suppressed the NF-κB and MAPKs subsequent gene expression of NFATc1 and c-Fos. In vivo studies, SA inhibited osteoclast function and exhibited bone protection effect in wear-particle-induced bone erosion model. Taken together, SA could attenuate osteoclast formation and wear particle-induced osteolysis by mediating RANKL signaling pathways. These data indicated that SA is a promising therapeutic natural compound for the treatment of osteoclast-related prosthesis loosening.

Surface Modification by Friction Stir Processing of Low-Carbon Steel: Microstructure Investigation and Wear Performance

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Sattari, Behnoosh; Shamanian, Morteza; Salimijazi, Farshid; Salehi, Mehdi

2018-02-01

A low-carbon steel sheet with a thickness of 5 mm was subjected to friction stir processing (FSP) by one to four different passes. The microstructures of different regions were characterized using the optical microscopy and electron backscatter diffraction. The Vickers micro-harness was measured at the distance of 200 μm below the processed surfaces. The influence of pass numbers (PNs) on wear resistance was studied in terms of coefficients of friction (CoFs), weight losses and wear rates. SEM topographies of the worn surfaces were also studied to evaluate the wear mechanisms. Microstructure observations showed that Widmänstatten ferrite plates were formed in stir zones (SZs) and heat affected zones. As PN increased, these grains were widened due to the increment of the carbon diffusivity and lengthened because of the high heat input and microstructure anisotropy. Besides, increasing the PN causes increasing of the hardness and wear resistance, simultaneously. Specifically, the wear rate in the SZ was reduced from 2.8 × 10-2 mm3 m-1 in base metal to 0.3 × 10-2 mm3 m-1 in sample which was subjected to 4 FSP passes. However, variation in PN had no considerable effect on CoFs. Oxidative wear mechanism was observed on the worn surface of the steel and the FSPed samples while more debris was formed by increasing the PNs.

Bufei Huoxue Capsule Attenuates PM2.5-Induced Pulmonary Inflammation in Mice

Directory of Open Access Journals (Sweden)

Yue Jing

2017-01-01

Full Text Available Atmospheric fine particulate matter 2.5 (PM 2.5 may carry many toxic substances on its surface and this may pose a public health threat. Epidemiological research indicates that cumulative ambient PM2.5 is correlated to morbidity and mortality due to pulmonary and cardiovascular diseases and cancer. Mitigating the toxic effects of PM2.5 is therefore highly desired. Bufei Huoxue (BFHX capsules have been used in China to treat pulmonary heart disease (cor pulmonale. Thus, we assessed the effects of BFHX capsules on PM2.5-induced pulmonary inflammation and the underlying mechanisms of action. Using Polysearch and Cytoscape 3.2.1 software, pharmacological targets of BFHX capsules in atmospheric PM2.5-related respiratory disorders were predicted and found to be related to biological pathways of inflammation and immune function. In a mouse model of PM2.5-induced inflammation established with intranasal instillation of PM2.5 suspension, BFHX significantly reduced pathological response and inflammatory mediators including IL-4, IL-6, IL-10, IL-8, TNF-α, and IL-1β. BFHX also reduced keratinocyte growth factor (KGF, secretory immunoglobulin A (sIgA, and collagen fibers deposition in lung and improved lung function. Thus, BFHX reduced pathological responses induced by PM2.5, possibly via regulation of inflammatory mediators in mouse lungs.

Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation.

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Chen, Rui; Zhong, Wei; Shao, Chen; Liu, Peijing; Wang, Cuiping; Wang, Zhongqun; Jiang, Meiping; Lu, Yi; Yan, Jinchuan

2018-02-01

Endoplasmic reticulum (ER) stress and inflammation contribute to pulmonary hypertension (PH) pathogenesis. Previously, we confirmed that docosahexaenoic acid (DHA) could improve hypoxia-induced PH. However, little is known about the link between DHA and monocrotaline (MCT)-induced PH. Our aims were, therefore, to evaluate the effects and molecular mechanisms of DHA on MCT-induced PH in rats. Rat PH was induced by MCT. Rats were treated with DHA daily in the prevention group (following MCT injection) and the reversal group (after MCT injection for 2 wk) by gavage. After 4 wk, mean pulmonary arterial pressure (mPAP), right ventricular (RV) hypertrophy index, and morphological and immunohistochemical analyses were evaluated. Rat pulmonary artery smooth muscle cells (PASMCs) were used to investigate the effects of DHA on cell proliferation stimulated by platelet-derived growth factor (PDGF)-BB. DHA decreased mPAP and attenuated pulmonary vascular remodeling and RV hypertrophy, which were associated with suppressed ER stress. DHA blocked the mitogenic effect of PDGF-BB on PASMCs and arrested the cell cycle via inhibiting nuclear factor of activated T cells-1 (NFATc1) expression and activation and regulating cell cycle-related proteins. Moreover, DHA ameliorated inflammation in lung and suppressed macrophage and T lymphocyte accumulation in lung and adventitia of resistance pulmonary arteries. These findings suggest that DHA could protect against MCT-induced PH by reducing ER stress, suppressing cell proliferation and inflammation.

Impacts of weathered tire debris on the development of Rana sylvatica larvae.

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Camponelli, Kimberly M; Casey, Ryan E; Snodgrass, Joel W; Lev, Steven M; Landa, Edward R

2009-02-01

Highway runoff has the potential to negatively impact receiving systems including stormwater retention ponds where highway particulate matter can accumulate following runoff events. Tire wear particles, which contain about 1% Zn by mass, make up approximately one-third of the vehicle derived particulates in highway runoff and therefore may serve as a stressor to organisms utilizing retention ponds as habitat. In this study, we focused on the potential contribution of tire debris to Zn accumulation by Rana sylvatica larvae and possible lethal or sublethal impacts resulting from exposure to weathered tire debris during development. Eggs and larvae were exposed to aged sediments (containing either ZnCl2 or tire particulate matter, both providing nominal concentrations of 1000 mg Zn kg(-1)) through metamorphosis. Water column Zn was elevated in both the ZnCl2 and tire treatments relative to the control treatment, indicating that aging allowed Zn leaching from tire debris to occur. Tissue Zn was also elevated for the ZnCl2 and tire treatments indicating that Zn in the treatments was available for uptake by the amphibians. Exposure to both ZnCl2 and tire treatments increased the time for larvae to complete metamorphosis in comparison with controls. We also observed that the longer the organisms took to complete metamorphosis, the smaller their mass at metamorphosis. Our results indicate that Zn leached from aged tire debris is bioavailable to developing R. sylvatica larvae and that exposure to tire debris amended sediments can result in measurable physiological outcomes to wood frogs that may influence population dynamics.

Impacts of weathered tire debris on the development of Rana sylvatica larvae

Science.gov (United States)

Camponelli, K.M.; Casey, R.E.; Snodgrass, J.W.; Lev, S.M.; Landa, E.R.

2009-01-01

Highway runoff has the potential to negatively impact receiving systems including stormwater retention ponds where highway particulate matter can accumulate following runoff events. Tire wear particles, which contain about 1% Zn by mass, make up approximately one-third of the vehicle derived particulates in highway runoff and therefore may serve as a stressor to organisms utilizing retention ponds as habitat. In this study, we focused on the potential contribution of tire debris to Zn accumulation by Rana sylvatica larvae and possible lethal or sublethal impacts resulting from exposure to weathered tire debris during development. Eggs and larvae were exposed to aged sediments (containing either ZnCl2 or tire particulate matter, both providing nominal concentrations of 1000 mg Zn kg-1) through metamorphosis. Water column Zn was elevated in both the ZnCl2 and tire treatments relative to the control treatment, indicating that aging allowed Zn leaching from tire debris to occur. Tissue Zn was also elevated for the ZnCl2 and tire treatments indicating that Zn in the treatments was available for uptake by the amphibians. Exposure to both ZnCl2 and tire treatments increased the time for larvae to complete metamorphosis in comparison with controls. We also observed that the longer the organisms took to complete metamorphosis, the smaller their mass at metamorphosis. Our results indicate that Zn leached from aged tire debris is bioavailable to developing R. sylvatica larvae and that exposure to tire debris amended sediments can result in measurable physiological outcomes to wood frogs that may influence population dynamics. ?? 2008 Elsevier Ltd.

Saturated fatty acid palmitate induces extracellular release of histone H3: A possible mechanistic basis for high-fat diet-induced inflammation and thrombosis

Energy Technology Data Exchange (ETDEWEB)

Shrestha, Chandan [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Ito, Takashi [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Kawahara, Ko-ichi [Department of Biomedical Engineering, Osaka Institute of Technology, Osaka (Japan); Shrestha, Binita; Yamakuchi, Munekazu; Hashiguchi, Teruto [Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Maruyama, Ikuro, E-mail: rinken@m3.kufm.kagoshima-u.ac.jp [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan)

2013-08-09

Highlights: •High-fat diet feeding and palmitate induces the release of nuclear protein histone H3. •ROS production and JNK signaling mediates the release of histone H3. •Extracellular histones induces proinflammatory and procoagulant response. -- Abstract: Chronic low-grade inflammation is a key contributor to high-fat diet (HFD)-related diseases, such as type 2 diabetes, non-alcoholic steatohepatitis, and atherosclerosis. The inflammation is characterized by infiltration of inflammatory cells, particularly macrophages, into obese adipose tissue. However, the molecular mechanisms by which a HFD induces low-grade inflammation are poorly understood. Here, we show that histone H3, a major protein component of chromatin, is released into the extracellular space when mice are fed a HFD or macrophages are stimulated with the saturated fatty acid palmitate. In a murine macrophage cell line, RAW 264.7, palmitate activated reactive oxygen species (ROS) production and JNK signaling. Inhibitors of these pathways dampened palmitate-induced histone H3 release, suggesting that the extracellular release of histone H3 was mediated, in part, through ROS and JNK signaling. Extracellular histone activated endothelial cells toexpress the adhesion molecules ICAM-1 and VCAM-1 and the procoagulant molecule tissue factor, which are known to contribute to inflammatory cell recruitment and thrombosis. These results suggest the possible contribution of extracellular histone to the pathogenesis of HFD-induced inflammation and thrombosis.

Saturated fatty acid palmitate induces extracellular release of histone H3: A possible mechanistic basis for high-fat diet-induced inflammation and thrombosis

International Nuclear Information System (INIS)

Shrestha, Chandan; Ito, Takashi; Kawahara, Ko-ichi; Shrestha, Binita; Yamakuchi, Munekazu; Hashiguchi, Teruto; Maruyama, Ikuro

2013-01-01

Highlights: •High-fat diet feeding and palmitate induces the release of nuclear protein histone H3. •ROS production and JNK signaling mediates the release of histone H3. •Extracellular histones induces proinflammatory and procoagulant response. -- Abstract: Chronic low-grade inflammation is a key contributor to high-fat diet (HFD)-related diseases, such as type 2 diabetes, non-alcoholic steatohepatitis, and atherosclerosis. The inflammation is characterized by infiltration of inflammatory cells, particularly macrophages, into obese adipose tissue. However, the molecular mechanisms by which a HFD induces low-grade inflammation are poorly understood. Here, we show that histone H3, a major protein component of chromatin, is released into the extracellular space when mice are fed a HFD or macrophages are stimulated with the saturated fatty acid palmitate. In a murine macrophage cell line, RAW 264.7, palmitate activated reactive oxygen species (ROS) production and JNK signaling. Inhibitors of these pathways dampened palmitate-induced histone H3 release, suggesting that the extracellular release of histone H3 was mediated, in part, through ROS and JNK signaling. Extracellular histone activated endothelial cells toexpress the adhesion molecules ICAM-1 and VCAM-1 and the procoagulant molecule tissue factor, which are known to contribute to inflammatory cell recruitment and thrombosis. These results suggest the possible contribution of extracellular histone to the pathogenesis of HFD-induced inflammation and thrombosis

Aortic VCAM-1: an early marker of vascular inflammation in collagen-induced arthritis.

Science.gov (United States)

Denys, Anne; Clavel, Gaëlle; Lemeiter, Delphine; Schischmanoff, Olivier; Boissier, Marie-Christophe; Semerano, Luca

2016-05-01

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). There are limited experimental data on vascular involvement in arthritis models. To study the link between CVD and inflammation in RA, we developed a model of vascular dysfunction and articular inflammation by collagen-induced arthritis (CIA) in C57Bl/6 (B6) mice. We studied the expression of vascular inflammatory markers in CIA with and without concomitant hyperlipidic diet (HD). Collagen-induced arthritis was induced with intradermal injection of chicken type-II collagen followed by a boost 21 days later. Mice with and without CIA were fed a standard diet or an HD for 12 weeks starting from the day of the boost. Arthritis severity was evaluated with a validated clinical score. Aortic mRNA levels of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS) and interleukin-17 were analysed by quantitative RT-PCR. Vascular cell adhesion molecule-1 localization in the aortic sinus was determined by immunohistochemistry. Atherosclerotic plaque presence was assessed in aortas. Collagen-induced arthritis was associated with increased expression of VCAM-1, independent of diet. VCAM-1 overexpression was detectable as early as 4 weeks after collagen immunization and persisted after 15 weeks. The HD induced atheroma plaque formation and aortic iNOS expression regardless of CIA. Concomitant CIA and HD had no additive effect on atheroma or VCAM-1 or iNOS expression. CIA and an HD diet induced a distinct and independent expression of large-vessel inflammation markers in B6 mice. This model may be relevant for the study of CVD in RA. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Motorcycle exhaust particles induce airway inflammation and airway hyperresponsiveness in BALB/C mice.

Science.gov (United States)

Lee, Chen-Chen; Liao, Jiunn-Wang; Kang, Jaw-Jou

2004-06-01

A number of large studies have reported that environmental pollutants from fossil fuel combustion can cause deleterious effects to the immune system, resulting in an allergic reaction leading to respiratory tract damage. In this study, we investigated the effect of motorcycle exhaust particles (MEP), a major pollutant in the Taiwan urban area, on airway inflammation and airway hyperresponsiveness in laboratory animals. BALB/c mice were instilled intratracheally (i.t.) with 1.2 mg/kg and 12 mg/kg of MEP, which was collected from two-stroke motorcycle engines. The mice were exposed 3 times i.t. with MEP, and various parameters for airway inflammation and hyperresponsiveness were sequentially analyzed. We found that MEP would induce airway and pulmonary inflammation characterized by infiltration of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid (BALF) and inflammatory cell infiltration in lung. In addition, MEP treatment enhanced BALF interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) cytokine levels and serum IgE production. Bronchial response measured by unrestrained plethysmography with methacholine challenge showed that MEP treatment induced airway hyperresponsiveness (AHR) in BALB/c mice. The chemical components in MEP were further fractionated with organic solvents, and we found that the benzene-extracted fraction exerts a similar biological effect as seen with MEP, including airway inflammation, increased BALF IL-4, serum IgE production, and induction of AHR. In conclusion, we present evidence showing that the filter-trapped particles emitted from the unleaded-gasoline-fueled two-stroke motorcycle engine may induce proinflammatory and proallergic response profiles in the absence of exposure to allergen.

The relationship of polyethylene wear to particle size, distribution, and number: A possible factor explaining the risk of osteolysis after hip arthroplasty

Czech Academy of Sciences Publication Activity Database

Gallo, J.; Šlouf, Miroslav; Goodman, S. B.

94B, č. 1 (2010), s. 171-177 ISSN 1552-4973 R&D Projects: GA MŠk 2B06096 Institutional research plan: CEZ:AV0Z40500505 Keywords : wear debris * polyethylene (UHMWPE) * periprosthetic osteolysis Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.220, year: 2010

TRANSPORT CHARACTERISTICS OF SELECTED PWR LOCA GENERATED DEBRIS

International Nuclear Information System (INIS)

MAJI, A. K.; MARSHALL, B.

2000-01-01

In the unlikely event of a Loss of Coolant Accident (LOCA) in a pressurized water reactor (PWR), break jet impingement would dislodge thermal insulation FR-om nearby piping, as well as other materials within the containment, such as paint chips, concrete dust, and fire barrier materials. Steam/water flows induced by the break and by the containment sprays would transport debris to the containment floor. Subsequently, debris would likely transport to and accumulate on the suction sump screens of the emergency core cooling system (ECCS) pumps, thereby potentially degrading ECCS performance and possibly even failing the ECCS. In 1998, the U. S. Nuclear Regulatory Commission (NRC) initiated a generic study (Generic Safety Issue-191) to evaluate the potential for the accumulation of LOCA related debris on the PWR sump screen and the consequent loss of ECCS pump net positive suction head (NPSH). Los Alamos National Laboratory (LANL), supporting the resolution of GSI-191, was tasked with developing a method for estimating debris transport in PWR containments to estimate the quantity of debris that would accumulate on the sump screen for use in plant specific evaluations. The analytical method proposed by LANL, to predict debris transport within the water that would accumulate on the containment floor, is to use computational fluid dynamics (CFD) combined with experimental debris transport data to predict debris transport and accumulation on the screen. CFD simulations of actual plant containment designs would provide flow data for a postulated accident in that plant, e.g., three-dimensional patterns of flow velocities and flow turbulence. Small-scale experiments would determine parameters defining the debris transport characteristics for each type of debris. The containment floor transport methodology will merge debris transport characteristics with CFD results to provide a reasonable and conservative estimate of debris transport within the containment floor pool and

The novel cytokine interleukin-33 activates acinar cell proinflammatory pathways and induces acute pancreatic inflammation in mice.

Directory of Open Access Journals (Sweden)

Duraisamy Kempuraj

Full Text Available Acute pancreatitis is potentially fatal but treatment options are limited as disease pathogenesis is poorly understood. IL-33, a novel IL-1 cytokine family member, plays a role in various inflammatory conditions but its role in acute pancreatitis is not well understood. Specifically, whether pancreatic acinar cells produce IL-33 when stressed or respond to IL-33 stimulation, and whether IL-33 exacerbates acute pancreatic inflammation is unknown.In duct ligation-induced acute pancreatitis in mice and rats, we found that (a IL-33 concentration was increased in the pancreas; (b mast cells, which secrete and also respond to IL-33, showed degranulation in the pancreas and lung; (c plasma histamine and pancreatic substance P concentrations were increased; and (d pancreatic and pulmonary proinflammatory cytokine concentrations were increased. In isolated mouse pancreatic acinar cells, TNF-α stimulation increased IL-33 release while IL-33 stimulation increased proinflammatory cytokine release, both involving the ERK MAP kinase pathway; the flavonoid luteolin inhibited IL-33-stimulated IL-6 and CCL2/MCP-1 release. In mice without duct ligation, exogenous IL-33 administration induced pancreatic inflammation without mast cell degranulation or jejunal inflammation; pancreatic changes included multifocal edema and perivascular infiltration by neutrophils and some macrophages. ERK MAP kinase (but not p38 or JNK and NF-kB subunit p65 were activated in the pancreas of mice receiving exogenous IL-33, and acinar cells isolated from the pancreas of these mice showed increased spontaneous cytokine release (IL-6, CXCL2/MIP-2α. Also, IL-33 activated ERK in human pancreatic tissue.As exogenous IL-33 does not induce jejunal inflammation in the same mice in which it induces pancreatic inflammation, we have discovered a potential role for an IL-33/acinar cell axis in the recruitment of neutrophils and macrophages and the exacerbation of acute pancreatic inflammation

Slit2 ameliorates renal inflammation and fibrosis after hypoxia-and lipopolysaccharide-induced epithelial cells injury in vitro

Energy Technology Data Exchange (ETDEWEB)

Zhou, Xiangjun [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Yao, Qisheng, E-mail: yymcyqs@126.com [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Sun, Xinbo; Gong, Xiaoxin; Yang, Yong; Chen, Congbo [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Shan, Guang [Department of Urology, Renmin Hospital of Wuhan University, Hubei (China)

2017-03-01

Hypoxic acute kidney injury (AKI) is often incompletely repaired and leads to chronic kidney disease (CKD), which is characterized by tubulointerstitial inflammation and fibrosis. The Slit2 family of secreted glycoproteins is expressed in the kidney, it has been shown to exert an anti-inflammatory activity and prevent ischemic renal injury in vivo. However, whether Slit2 reduces renal fibrosis and inflammation after hypoxic and inflammatory epithelial cells injury in vitro remains unknown. In this study, we aimed to evaluate whether Slit2 ameliorated fibrosis and inflammation in two renal epithelial cells line challenged with hypoxia and lipopolysaccharide (LPS). Renal epithelial cells were treated with hypoxia and LPS to induce cell injury. Hoechst staining and Western blot analysis was conducted to examine epithelial cells injury. Immunofluorescence staining and Western blot analysis was performed to evaluate tubulointerstitial fibrosis. Real-time polymerase chain reaction (PCR) tested the inflammatory factor interleukin (IL)−1β and tumor necrosis factor (TNF)-α, and Western blot analysis determined the hypoxia-inducible factor (HIF)−1α, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Results revealed that hypoxia induced epithelial cells apoptosis, inflammatory factor IL-1β and TNF-α release and tubulointerstitial fibrosis. LPS could exacerbate hypoxia -induced epithelial cells apoptosis, IL-1β and TNF-α release and fibrosis. Slit2 reduced the expression of fibronectin, the rate of epithelial cell apoptosis, and the expression of inflammatory factor. Slit2 could also inhibit the expression of TLR4 and NF-κB, but not the expression of HIF-1α. Therefore, Slit2 attenuated inflammation and fibrosis after LPS- and hypoxia-induced epithelial cells injury via the TLR4/NF-κB signaling pathway, but not depending on the HIF-1α signaling pathway. - Highlights: • Slit2 ameliorates inflammation after hypoxia-and LPS-induced epithelial cells injury

The hexane fraction of Ardisia crispa Thunb. A. DC. roots inhibits inflammation-induced angiogenesis

Science.gov (United States)

2013-01-01

Background Ardisia crispa (Myrsinaceae) is used in traditional Malay medicine to treat various ailments associated with inflammation, including rheumatism. The plant’s hexane fraction was previously shown to inhibit several diseases associated with inflammation. As there is a strong correlation between inflammation and angiogenesis, we conducted the present study to investigate the anti-angiogenic effects of the plant’s roots in animal models of inflammation-induced angiogenesis. Methods We first performed phytochemical screening and high-performance liquid chromatography (HPLC) fingerprinting of the hexane fraction of Ardisia crispa roots ethanolic extract (ACRH) and its quinone-rich fraction (QRF). The anti-inflammatory properties of ACRH and QRF were tested using the Miles vascular permeability assay and the murine air pouch granuloma model following oral administration at various doses. Results Preliminary phytochemical screening of ACRH revealed the presence of flavonoids, triterpenes, and tannins. The QRF was separated from ACRH (38.38% w/w) by column chromatography, and was isolated to yield a benzoquinonoid compound. The ACRH and QRF were quantified by HPLC. The LD50 value of ACRH was 617.02 mg/kg. In the Miles vascular permeability assay, the lowest dose of ACRH (10 mg/kg) and all doses of QRF significantly reduced vascular endothelial growth factor (VEGF)-induced hyperpermeability, when compared with the vehicle control. In the murine air pouch granuloma model, ACRH and QRF both displayed significant and dose-dependent anti-inflammatory effects, without granuloma weight. ACRH and QRF significantly reduced the vascular index, but not granuloma tissue weight. Conclusions In conclusion, both ACRH and QRF showed potential anti-inflammatory properties in a model of inflammation-induced angiogenesis model, demonstrating their potential anti-angiogenic properties. PMID:23298265

Experimental fretting-wear studies of steam generator materials

International Nuclear Information System (INIS)

Fisher, N.J.; Chow, A.B.; Weckwerth, M.K.

1994-01-01

Flow-induced vibration of steam generator tubes results in fretting-wear damage due to impacting and rubbing of the tubes against their supports. This damage can be predicted by computing tube response to flow-induced excitation forces using analytical techniques, and then relating this response to resultant wear damage using experimentally-derived wear coefficients. Fretting-wear of steam generator materials has been studied experimentally at Chalk River Laboratories for two decades. Tests are conducted in machines that simulate steam generator environmental conditions and tube-to-support dynamic interactions. Different tube and support materials, tube-to-support clearances and tube support geometries have been studied. As well, the effect of environmental conditions, such as temperature, oxygen content, pH and chemistry control additive, have been investigated. Early studies showed that damage was related to contact force as long as other parameters, such as geometry and motion were held constant. Later studies have shown that damage is related to a parameter called work-rate, which combines both contact force and sliding distance. Results of short- and long-term fretting-wear tests for CANDU steam generator materials at realistic environmental conditions are presented. These results demonstrate that work-rate is appropriate correlating parameter for impact-sliding interaction

Photonic Low Cost Micro-Sensor for in-Line Wear Particle Detection in Flowing Lube Oils

Directory of Open Access Journals (Sweden)

Jon Mabe

2017-03-01

Full Text Available The presence of microscopic particles in suspension in industrial fluids is often an early warning of latent or imminent failures in the equipment or processes where they are being used. This manuscript describes work undertaken to integrate different photonic principles with a micro- mechanical fluidic structure and an embedded processor to develop a fully autonomous wear debris sensor for in-line monitoring of industrial fluids. Lens-less microscopy, stroboscopic illumination, a CMOS imager and embedded machine vision technologies have been merged to develop a sensor solution that is able to detect and quantify the number and size of micrometric particles suspended in a continuous flow of a fluid. A laboratory test-bench has been arranged for setting up the configuration of the optical components targeting a static oil sample and then a sensor prototype has been developed for migrating the measurement principles to real conditions in terms of operating pressure and flow rate of the oil. Imaging performance is quantified using micro calibrated samples, as well as by measuring real used lubricated oils. Sampling a large fluid volume with a decent 2D spatial resolution, this photonic micro sensor offers a powerful tool at very low cost and compacted size for in-line wear debris monitoring.

miR-217 Regulates Ethanol-Induced Hepatic Inflammation by Disrupting Sirtuin 1–Lipin-1 Signaling

OpenAIRE

Yin, Huquan; Liang, Xiaomei; Jogasuria, Alvin; Davidson, Nicholas O.; You, Min

2015-01-01

Ethanol-mediated injury, combined with gut-derived lipopolysaccharide (LPS), provokes generation of proinflammatory cytokines in Kupffer cells, causing hepatic inflammation. Among the mediators of these effects, miR-217 aggravates ethanol-induced steatosis in hepatocytes. However, the role of miR-217 in ethanol-induced liver inflammation process is unknown. Here, we examined the role of miR-217 in the responses to ethanol, LPS, or a combination of ethanol and LPS in RAW 264.7 macrophages and ...

Silica-induced Chronic Inflammation Promotes Lung Carcinogenesis in the Context of an Immunosuppressive Microenvironment

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Javier Freire

2013-08-01

Full Text Available The association between inflammation and lung tumor development has been clearly demonstrated. However, little is known concerning the molecular events preceding the development of lung cancer. In this study, we characterize a chemically induced lung cancer mouse model in which lung cancer developed in the presence of silicotic chronic inflammation. Silica-induced lung inflammation increased the incidence and multiplicity of lung cancer in mice treated with N-nitrosodimethylamine, a carcinogen found in tobacco smoke. Histologic and molecular analysis revealed that concomitant chronic inflammation contributed to lung tumorigenesis through induction of preneoplastic changes in lung epithelial cells. In addition, silica-mediated inflammation generated an immunosuppressive microenvironment in which we observed increased expression of programmed cell death protein 1 (PD-1, transforming growth factor-β1, monocyte chemotactic protein 1 (MCP-1, lymphocyte-activation gene 3 (LAG3, and forkhead box P3 (FOXP3, as well as the presence of regulatory T cells. Finally, the K-RAS mutational profile of the tumors changed from Q61R to G12D mutations in the inflammatory milieu. In summary, we describe some of the early molecular changes associated to lung carcinogenesis in a chronic inflammatory microenvironment and provide novel information concerning the mechanisms underlying the formation and the fate of preneoplastic lesions in the silicotic lung.

Theoretical-experimental analysis of the fretting/impact wear in fuel rods

International Nuclear Information System (INIS)

Pecos, Luis F.

2001-01-01

Nuclear power plant fuel elements are subjected to flow induced vibrations. A consequence of these vibrations is impact/fretting wear in fuel rods or sliding shoes. Because of the difficulties to assert the mechanism of impact/fretting wear phenomenon it is necessary to use semiempirical formulations in order to predict the wear rate of the components. The results of a series of experiments with Zr-4 specimens are presented in this work. A parameter called 'work-rate' was used to normalize the wear rates and interpret the results in terms of wear coefficient. (author) [es

DNA damage-induced inflammation and nuclear architecture.

Science.gov (United States)

Stratigi, Kalliopi; Chatzidoukaki, Ourania; Garinis, George A

2017-07-01

Nuclear architecture and the chromatin state affect most-if not all- DNA-dependent transactions, including the ability of cells to sense DNA lesions and restore damaged DNA back to its native form. Recent evidence points to functional links between DNA damage sensors, DNA repair mechanisms and the innate immune responses. The latter raises the question of how such seemingly disparate processes operate within the intrinsically complex nuclear landscape and the chromatin environment. Here, we discuss how DNA damage-induced immune responses operate within chromatin and the distinct sub-nuclear compartments highlighting their relevance to chronic inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ultrastructural analysis of nanoparticles and ions released in periprosthetic membranes.

Science.gov (United States)

Sabbatini, Maurizio; Gatti, Giorgio; Renò, Filippo; Bosetti, Michela; Marchese, Leonardo; Cannas, Mario

2014-12-30

The distribution and relationship of hydroxyapatite debris, nanometric organic and metal wear particles and metal ions on periimplant interface membranes following aseptic and septic arthroplastic loosening were investigated. Scanning electron microscopy and X-ray spectroscopic analysis were used to analyze debris and ion distribution. Hydroxyapatite debris appeared with different morphology in a particular distribution among several membranes. These differences may reflect the occurrence of different friction forces taking place between prosthesis and bone interface in the several types of prostheses studied. Metal wear particles were detected in greater numbers in membranes from noncemented prostheses compared with those from cemented ones. In contrast, more organic particles were present in membrane from cemented prosthesis. No differences were observed between aseptic and septic membranes. Our findings support the need to evaluate the occurrence of friction forces that periprosthetic bone debris production may induce to exacerbate cellular reactivity. Furthermore, cellular engulfment of debris and the high level of different ions released indicate the occurrence of a toxic environment that may induce failure of any reparative pathways.

Ficolins do not alter host immune responses to lipopolysaccharide-induced inflammation in vivo

DEFF Research Database (Denmark)

Genster, Ninette; Østrup, Olga; Schjalm, Camilla

2017-01-01

. Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, we investigated ficolin deficient mice during a lipopolysaccharide (LPS)-induced model of systemic inflammation. Although murine serum ficolin was shown to bind LPS in vitro, there was no difference...... an unaltered spleen transcriptome profile in ficolin deficient mice compared to wildtype mice. Collectively, results from this study demonstrate that ficolins are not involved in host response to LPS-induced systemic inflammation.......Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested...

Vibrational characteristics and wear of fuel rods

International Nuclear Information System (INIS)

Schmugar, K.L.

1977-01-01

Fuel rod wear, due to vibration, is a continuing concern in the design of liquid-cooled reactors. In my report, the methodology and models that are used to predict fuel rod vibrational response and vibratory wear, in a light water reactor environment, are discussed. This methodology is being followed at present in the design of Westinghouse Nuclear Fuel. Fuel rod vibrations are expressed as the normal bending modes, and sources of rod vibration are examined with special emphasis on flow-induced mechanisms in the stable flow region. In a typical Westinghouse PWR fuel assembly design, each fuel rod is supported at multiple locations along the rod axis by a square-shaped 'grid cell'. For a fuel rod /grid support system, the development of small oscillatory motions, due to fluid flow at the rod/grid interface, results in material wear. A theoretical wear mode is developed using the Archard Theory of Adhesive Wear as the basis. Without question certainty, fretting wear becomes a serious problem if it progresses to the stage where the fuel cladding is penetrated and fuel is exposed to the coolant. Westinghouse fuel is designed to minimize fretting wear by limiting the relative motion between the fuel rod and its supports. The wear producing motion between the fuel rod and its supports occurs when the vibration amplitude exceeds the slippage threshold amplitude

Study on the Correlation Between Dynamical Behavior and Friction/Wear Mechanism Under the Effect of Grooves

Science.gov (United States)

Zhu, Z. Y.; Mo, J. L.; Wang, D. W.; Zhao, J.; Zhu, M. H.; Zhou, Z. R.

2018-04-01

In this work, the interfacial friction and wear and vibration characteristics are studied by sliding a chromium bearing steel ball (AISI 52100) over both multi-grooved and single-grooved forged steel disks (20CrMnMo) at low and high rotating speeds in order to reveal the effect mechanism of groove-textured surface on tribological behaviors. The results show that the grooves modify the contact state of the ball and the disk at the contact interface. This consequently causes variations in the normal displacement, normal force, and friction force signals. The changes in these three signals become more pronounced with increasing groove width at a low speed. The collision behavior between the ball and the groove increase the amplitude of vibration acceleration at a high speed. The test results suggest that grooves with appropriate widths could trap wear debris on the ball surface while avoiding a strong collision between the disk and the ball, resulting in an improvement in the wear states.

Comparative evaluation of apically extruded debris with V-Taper, ProTaper Next, and the Self-adjusting File systems.

Science.gov (United States)

Vyavahare, Nishant K; Raghavendra, Srinidhi Surya; Desai, Niranjan N

2016-01-01

Complete cleaning of the root canal is the goal for ensuring success in endodontics. Removal of debris plays an important role in achieving this goal. In spite of advancements in instrument design, apical extrusion of debris remains a source of inflammation in the periradicular region. To comparatively evaluate the amount of apically extruded debris with V-Taper, ProTaper Next, and the self-adjusting File (SAF) system. Sixty-four extracted human mandibular teeth with straight root canals were taken. Access openings were done and working length determined. The samples were randomly divided into three groups: Group I - V-Taper files (n = 20), Group II - ProTaper Next (n = 20), Group III - SAF (n = 20). Biomechanical preparation was completed and the debris collected in vials to be quantitatively determined. The data obtained was statistically analyzed using ANOVA and post hoc Tukey's test. All the specimens showed apical debris extrusion. SAF showed significantly less debris extrusion compared to V-Taper and ProTaper Next (P endodontic instruments. This indicates that the incidence of inter-treatment flare-ups due to debris extrusion would be less with the SAF.

Tolerogenic CX3CR1+ B cells suppress food allergy-induced intestinal inflammation in mice.

Science.gov (United States)

Liu, Z Q; Wu, Y; Song, J P; Liu, X; Liu, Z; Zheng, P Y; Yang, P C

2013-10-01

B lymphocytes are an important cell population of the immune regulation; their role in the regulation of food allergy has not been fully understood yet. This study aims to investigate the role of a subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T cells (Treg) and in the suppression of food allergy-induced intestinal inflammation in mice. The intestinal mucosa-derived CD5+ CD19+ CX3CR1+ TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper (Th)2 inflammation was established to assess the immune regulatory role of this subpopulation of TolBCs. A subpopulation of CD5+ CD19+ CX3CR1+ B cells was detected in the mouse intestinal mucosa. The cells also expressed transforming growth factor (TGF)-β and carried integrin alpha v beta 6 (αvβ6). Exposure to recombinant αvβ6 and anti-IgM antibody induced naive B cells to differentiate into the TGF-β-producing TolBCs. Coculturing this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs. Adoptive transfer with the TolBCs markedly suppressed the food allergy-induced intestinal Th2 pattern inflammation in mice. CD5+ CD19+ CX3CR1+ TolBCs are capable of inducing Tregs in the intestine and suppress food allergy-related Th2 pattern inflammation in mice. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eupafolin nanoparticles protect HaCaT keratinocytes from particulate matter-induced inflammation and oxidative stress

Science.gov (United States)

Lin, Zih-Chan; Lee, Chiang-Wen; Tsai, Ming-Horng; Ko, Horng-Huey; Fang, Jia-You; Chiang, Yao-Chang; Liang, Chan-Jung; Hsu, Lee-Fen; Hu, Stephen Chu-Sung; Yen, Feng-Lin

2016-01-01

Exposure to particulate matter (PM), a major form of air pollution, can induce oxidative stress and inflammation and may lead to many diseases in various organ systems including the skin. Eupafolin, a flavonoid compound derived from Phyla nodiflora, has been previously shown to exhibit various pharmacological activities, including antioxidant and anti-inflammatory effects. Unfortunately, eupafolin is characterized by poor water solubility and skin penetration, which limits its clinical applications. To address these issues, we successfully synthesized a eupafolin nanoparticle delivery system (ENDS). Our findings showed that ENDS could overcome the physicochemical drawbacks of raw eupafolin with respect to water solubility and skin penetration, through reduction of particle size and formation of an amorphous state with hydrogen bonding. Moreover, ENDS was superior to raw eupafolin in attenuating PM-induced oxidative stress and inflammation in HaCaT keratinocytes, by mediating the antioxidant pathway (decreased reactive oxygen species production and nicotinamide adenine dinucleotide phosphate oxidase activity) and anti-inflammation pathway (decreased cyclooxygenase-2 expression and prostaglandin E2 production through downregulation of mitogen-activated protein kinase and nuclear factor-κB signaling). In summary, ENDS shows better antioxidant and anti-inflammatory activities than raw eupafolin through improvement of water solubility and skin penetration. Therefore, ENDS may potentially be used as a medicinal drug and/or cosmeceutical product to prevent PM-induced skin inflammation. PMID:27570454

MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment

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Inge Van Hove

2016-11-01

Full Text Available Matrix metalloproteinase-3 (MMP-3 is known to mediate neuroinflammatory processes by activating microglia, disrupting blood–central nervous system barriers and supporting neutrophil influx into the brain. In addition, the posterior part of the eye, more specifically the retina, the retinal pigment epithelium (RPE and the blood–retinal barrier, is affected upon neuroinflammation, but a role for MMP-3 during ocular inflammation remains elusive. We investigated whether MMP-3 contributes to acute inflammation in the eye using the endotoxin-induced uveitis (EIU model. Systemic administration of lipopolysaccharide induced an increase in MMP-3 mRNA and protein expression level in the posterior part of the eye. MMP-3 deficiency or knockdown suppressed retinal leukocyte adhesion and leukocyte infiltration into the vitreous cavity in mice subjected to EIU. Moreover, retinal and RPE mRNA levels of intercellular adhesion molecule 1 (Icam1, interleukin 6 (Il6, cytokine-inducible nitrogen oxide synthase (Nos2 and tumor necrosis factor α (Tnfα, which are key molecules involved in EIU, were clearly reduced in MMP-3 deficient mice. In addition, loss of MMP-3 repressed the upregulation of the chemokines monocyte chemoattractant protein (MCP-1 and (C-X-C motif ligand 1 (CXCL1. These findings suggest a contribution of MMP-3 during EIU, and its potential use as a therapeutic drug target in reducing ocular inflammation.

SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes

NARCIS (Netherlands)

Diepen, van Janna A.; Robben, Joris H.; Hooiveld, Guido J.; Carmone, Claudia; Alsady, Mohammad; Boutens, Lily; Bekkenkamp-Grovenstein, Melissa; Hijmans, Anneke; Engelke, Udo F.H.; Wevers, Ron A.; Netea, Mihai G.; Tack, Cees J.; Stienstra, Rinke; Deen, Peter M.T.

2017-01-01

Aims/hypothesis: Obesity induces macrophages to drive inflammation in adipose tissue, a crucial step towards the development of type 2 diabetes. The tricarboxylic acid (TCA) cycle intermediate succinate is released from cells under metabolic stress and has recently emerged as a metabolic signal

Acrolein exposure suppresses antigen-induced pulmonary inflammation

Science.gov (United States)

2013-01-01

Background Adverse health effects of tobacco smoke arise partly from its influence on innate and adaptive immune responses, leading to impaired innate immunity and host defense. The impact of smoking on allergic asthma remains unclear, with various reports demonstrating that cigarette smoke enhances asthma development but can also suppress allergic airway inflammation. Based on our previous findings that immunosuppressive effects of smoking may be largely attributed to one of its main reactive electrophiles, acrolein, we explored the impact of acrolein exposure in a mouse model of ovalbumin (OVA)-induced allergic asthma. Methods C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection with the adjuvant aluminum hydroxide on days 0 and 7, and challenged with aerosolized OVA on days 14–16. In some cases, mice were also exposed to 5 ppm acrolein vapor for 6 hrs/day on days 14–17. Lung tissues or brochoalveolar lavage fluids (BALF) were collected either 6 hrs after a single initial OVA challenge and/or acrolein exposure on day 14 or 48 hrs after the last OVA challenge, on day 18. Inflammatory cells and Th1/Th2 cytokine levels were measured in BALF, and lung tissue samples were collected for analysis of mucus and Th1/Th2 cytokine expression, determination of protein alkylation, cellular thiol status and transcription factor activity. Results Exposure to acrolein following OVA challenge of OVA-sensitized mice resulted in markedly attenuated allergic airway inflammation, demonstrated by decreased inflammatory cell infiltrates, mucus hyperplasia and Th2 cytokines. Acrolein exposure rapidly depleted lung tissue glutathione (GSH) levels, and induced activation of the Nrf2 pathway, indicated by accumulation of Nrf2, increased alkylation of Keap1, and induction of Nrf2-target genes such as HO-1. Additionally, analysis of inflammatory signaling pathways showed suppressed activation of NF-κB and marginally reduced activation of JNK in acrolein

MiR-146a regulates PM1 -induced inflammation via NF-κB signaling pathway in BEAS-2B cells.

Science.gov (United States)

Liu, Limin; Wan, Chong; Zhang, Wei; Guan, Longfei; Tian, Guoxiong; Zhang, Fang; Ding, Wenjun

2018-04-18

Exposure to particulate matter (PM) leads to kinds of cardiopulmonary diseases, such as asthma, COPD, arrhythmias, lung cancer, etc., which are related to PM-induced inflammation. We have found that PM 2.5 (aerodynamics diameter <2.5 µm) exposure induces inflammatory response both in vivo and in vitro. Since the toxicity of PM is tightly associated with its size and components, PM 1 (aerodynamics diameter <1.0 µm) is supposed to be more toxic than PM 2.5 . However, the mechanism of PM 1 -induced inflammation is not clear. Recently, emerging evidences prove that microRNAs play a vital role in regulating inflammation. Therefore, we studied the regulation of miR-146a in PM 1 -induced inflammation in human lung bronchial epithelial BEAS-2B cells. The results show that PM 1 induces the increase of IL-6 and IL-8 in BEAS-2B cells and up-regulates the miR-146a expression by activating NF-κB signaling pathway. Overexpressed miR-146a prevents the nuclear translocation of p65 through inhibiting the IRAK1/TRAF6 expression, and downregulates the expression of IL-6 and IL-8. Taken together, these results demonstrate that miR-146a can negatively feedback regulate PM 1 -induced inflammation via NF-κB signaling pathway in BEAS-2B cells. © 2018 Wiley Periodicals, Inc.

Contact damage failure analyses of fretting wear behavior of the metal stem titanium alloy-bone cement interface.

Science.gov (United States)

Zhang, Lanfeng; Ge, Shirong; Liu, Hongtao; Wang, Qingliang; Wang, Liping; Xian, Cory J

2015-11-01

Although cemented titanium alloy is not favored currently in the Western world for its poor clinical and radiography outcomes, its lower modulus of elasticity and good biocompatibility are instrumental for its ability supporting and transforming physical load, and it is more suitable for usage in Chinese and Japanese populations due to their lower body weights and unique femoral characteristics. Through various friction tests of different cycles, loads and conditions and by examining fretting hysteresis loops, fatigue process curves and wear surfaces, the current study investigated fretting wear characteristics and wear mechanism of titanium alloy stem-bone cement interface. It was found that the combination of loads and displacement affected the wear quantity. Friction coefficient, which was in an inverse relationship to load under the same amplitude, was proportional to amplitudes under the same load. Additionally, calf serum was found to both lubricate and erode the wear interface. Moreover, cement fatigue contact areas appeared black/oxidative in dry and gruel in 25% calf serum. Fatigue scratches were detected within contact areas, and wear scars were found on cement and titanium surfaces, which were concave-shaped and ring concave/ convex-shaped, respectively. The coupling of thermoplastic effect and minimal torque damage has been proposed to be the major reason of contact damage. These data will be important for further studies analyzing metal-cement interface failure performance and solving interface friction and wear debris production issues. Copyright © 2015 Elsevier Ltd. All rights reserved.

One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice.

Science.gov (United States)

Waise, T M Zaved; Toshinai, Koji; Naznin, Farhana; NamKoong, Cherl; Md Moin, Abu Saleh; Sakoda, Hideyuki; Nakazato, Masamitsu

2015-09-04

A high-fat diet (HFD) induces inflammation in systemic organs including the hypothalamus, resulting in obesity and diabetes. The vagus nerve connects the visceral organs and central nervous system, and the gastric-derived orexigenic peptide ghrelin transmits its starvation signals to the hypothalamus via the vagal afferent nerve. Here we investigated the inflammatory response in vagal afferent neurons and the hypothalamus in mice following one day of HFD feeding. This treatment increased the number of macrophages/microglia in the nodose ganglion and hypothalamus. Furthermore, one-day HFD induced expression of Toll-like receptor 4 in the goblet cells of the colon and upregulated mRNA expressions of the proinflammatory biomarkers Emr1, Iba1, Il6, and Tnfα in the nodose ganglion and hypothalamus. Both subcutaneous administration of ghrelin and celiac vagotomy reduced HFD-induced inflammation in these tissues. HFD intake triggered inflammatory responses in the gut, nodose ganglion, and subsequently in the hypothalamus within 24 h. These findings suggest that the vagal afferent nerve may transfer gut-derived inflammatory signals to the hypothalamus via the nodose ganglion, and that ghrelin may protect against HFD-induced inflammation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Development of a fiber-coupled laser-induced breakdown spectroscopy instrument for analysis of underwater debris in a nuclear reactor core

International Nuclear Information System (INIS)

Saeki, Morihisa; Iwanade, Akio; Ohba, Hironori; Ito, Chikara; Wakaida, Ikuo; Thornton, Blair; Sakka, Tetsuo

2014-01-01

To inspect the post-accident nuclear core reactor of the TEPCO Fukushima Daiichi nuclear power plant (F1-NPP), a transportable fiber-coupled laser-induced breakdown spectroscopy (LIBS) instrument has been developed. The developed LIBS instrument was designed to analyze underwater samples in a high-radiation field by single-pulse breakdown with gas flow or double-pulse breakdown. To check the feasibility of the assembled fiber-coupled LIBS instrument for the analysis of debris material (mixture of the fuel core, fuel cladding, construction material and so on) in the F1-NPP, we investigated the influence of the radiation dose on the optical transmittance of the laser delivery fiber, compared data quality among various LIBS techniques for an underwater sample and studied the feasibility of the fiber-coupled LIBS system in an analysis of the underwater sample of the simulated debris in F1-NPP. In a feasible study conducted by using simulated debris, which was a mixture of CeO 2 (surrogate of UO 2 ), ZrO 2 and Fe, we selected atomic lines suitable for the analysis of materials, and prepared calibration curves for the component elements. The feasible study has guaranteed that the developed fiber-coupled LIBS system is applicable for analyzing the debris materials in the F1-NPP. (author)

3D finite element modeling of sliding wear

Science.gov (United States)

Buentello Hernandez, Rodolfo G.

Wear is defined as "the removal of material volume through some mechanical process between two surfaces". There are many mechanical situations that can induce wear and each can involve many wear mechanisms. This research focuses on the mechanical wear due to dry sliding between two surfaces. Currently there is a need to identify and compare materials that would endure sliding wear under severe conditions such as high velocities. The high costs associated with the field experimentation of systems subject to high-speed sliding, has prevented the collection of the necessary data required to fully characterize this phenomena. Simulating wear through Finite Elements (FE) would enable its prediction under different scenarios and would reduce experimentation costs. In the aerospace, automotive and weapon industries such a model can aid in material selection, design and/or testing of systems subjected to wear in bearings, gears, brakes, gun barrels, slippers, locomotive wheels, or even rocket test tracks. The 3D wear model presented in this dissertation allows one to reasonably predict high-speed sliding mechanical wear between two materials. The model predictions are reasonable, when compared against those measured on a sled slipper traveling over the Holloman High Speed Tests Track. This slipper traveled a distance of 5,816 meters in 8.14 seconds and reached a maximum velocity of 1,530 m/s.

Fretting wear behaviour of TiC/Ti(C,N)/TiN multi-layer coatings at elevated temperature in gross slip regime

International Nuclear Information System (INIS)

Liu Hanwei; Huang Kunpeng; Zhu Minhao; Zhou Zhongrong

2005-01-01

Tic/Ti(C,N)/TiN multi-layer coatings are prepared on the 1Cr13 stainless steel substrate by the technique of Chemical Vapour Deposition, and the fretting wear behaviour of 1Cr13 stainless steel and TiC/Ti(C,N)/TiN coatings are investigated and studied controversially from 25 degree C to 400 degree C in the gross slip regime. It shows that the temperature has great influence on the fretting wear in the gross slip regime for the 1Cr13 stainless steel but little for Ti/C/Ti(C,N)/TiN multi-layer coatings. With the temperature increasing, the friction coefficient and the wear volume of the 1Cr13 alloy decreases and the wear volume of TiC/Ti(C, N)/TiN multi-layer coatings is invariant. TiC/Ti(C,N)/TiN multi-layer coatings have better wear-resistant capability than the 1Cr13 stainless steel, but the wear volume of the substrate increases greatly because of the grain-abrasion resulted from hard debris when TiC/Ti(C,N)/TiN multi-layer coatings are ground off. (authors)

Memory Deficits Induced by Inflammation Are Regulated by α5-Subunit-Containing GABAA Receptors

Directory of Open Access Journals (Sweden)

Dian-Shi Wang

2012-09-01

Full Text Available Systemic inflammation causes learning and memory deficits through mechanisms that remain poorly understood. Here, we studied the pathogenesis of memory loss associated with inflammation and found that we could reverse memory deficits by pharmacologically inhibiting α5-subunit-containing γ-aminobutyric acid type A (α5GABAA receptors and deleting the gene associated with the α5 subunit. Acute inflammation reduces long-term potentiation, a synaptic correlate of memory, in hippocampal slices from wild-type mice, and this reduction was reversed by inhibition of α5GABAA receptor function. A tonic inhibitory current generated by α5GABAA receptors in hippocampal neurons was increased by the key proinflammatory cytokine interleukin-1β through a p38 mitogen-activated protein kinase signaling pathway. Interleukin-1β also increased the surface expression of α5GABAA receptors in the hippocampus. Collectively, these results show that α5GABAA receptor activity increases during inflammation and that this increase is critical for inflammation-induced memory deficits.

Effect of Artocarpus communis Extract on UVB Irradiation-Induced Oxidative Stress and Inflammation in Hairless Mice

Directory of Open Access Journals (Sweden)

Feng-Lin Yen

2013-02-01

Full Text Available Administration of antioxidants and anti-inflammatory agents is an effective strategy for preventing ultraviolet (UV irradiation-induced skin damage. Artocarpus communis possesses several pharmacological activities, such as antioxidant, anticancer and anti-inflammation. However, the photoprotective activity of methanol extract of A. communis heartwood (ACM in ultraviolet irradiation-induced skin damage has not yet been investigated. The present study was performed using ultraviolet absorption, histopathological observation, antioxidant and anti-inflammation assays to elucidate the mechanism of the photoprotective activity of ACM. Our results indicated that ACM displayed a UVA and UVB absorption effect and then effectively decreased scaly skin, epidermis thickness and sunburn cells during ultraviolet irradiation in hairless mice. ACM not only decreased ultraviolet irradiation-mediated oxidative stress, including lowering the overproduction of reactive oxygen species and lipid peroxidation (p < 0.05, but also reduced the levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α and interleukin 1β. Additionally, ACM can decrease the synthesis of cytosolic phospholipase A2, cyclooxygenase, inducible nitric oxide synthase and vascular cell adhesion molecular-1 via inhibiting TNF-α-independent pathways (p < 0.05 in UVB-mediated inflammation and formation of sunburn cells. Consequently, we concluded that ACM extract has a photoprotective effect against UVB-induced oxidative stress and inflammation due to its sunscreen property, and its topical formulations may be developed as therapeutic and/or cosmetic products in further studies.

Effect of Gmelina arborea Roxb in experimentally induced inflammation and nociception

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Yogesh A Kulkarni

2013-01-01

Full Text Available Background: Gmelina arborea Roxb (Verbenaceae, also known as "Gambhari", is an important medicinal plant in the Ayurveda. There are no meticulous scientific reports on effect of the plant on inflammation and pain. Objective: To study the anti-inflammatory and anti-nociceptive properties of aqueous extracts (AE and methanol extracts (ME of G. arborea. Materials and Methods: The AE and ME of stembark of G. arborea was prepared by cold maceration and Soxhlet extraction technique respectively. Anti-inflammatory activity was determined in Wistar albino rats in a model of acute plantar inflammation induced by carrageenan. The anti-nociceptive activity was evaluated by using hot plate test and writhing test in Swiss albino mice. Significant differences between the experimental groups were assessed by analysis of variance. Results: AE and ME at dose of 500 mg/kg showed maximum inhibition in carrageenan induced inflammation up to 30.15 and 31.21% respectively. In hot plate test, the AE and ME showed the maximum response of 8.8 ± 0.97 (P < 0.01 and 8.2 ± 1.24 (P < 0.01 respectively at dose of 500 mg/kg when compared with control. AE showed maximum inhibition of writhing response (84.3% as compared to ME (77.9% in writhing test at a dose of 500 mg/kg. Conclusion: The findings suggested that G. arborea possess significant anti-inflammatory and anti-nociceptive activities.

Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

Science.gov (United States)

Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

2015-01-01

Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation

International Nuclear Information System (INIS)

Zhang, Da-Gang; Zhang, Cheng; Wang, Jun-Xian; Wang, Bi-Wei; Wang, Hua; Zhang, Zhi-Hui; Chen, Yuan-Hua; Lu, Yan; Tao, Li; Wang, Jian-Qing; Chen, Xi; Xu, De-Xiang

2017-01-01

The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl 4 )-induced acute liver injury. Mice were intraperitoneally injected with CCl 4 (0.15 ml/kg). In CCl 4 + OCA group, mice were orally with OCA (5 mg/kg) 48, 24 and 1 h before CCl 4 . As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl 4 -induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited CCl 4 -induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl 4 -induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl 4 -induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl 4 -induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl 4 -induced acute liver injury. These results suggest that OCA protects against CCl 4 -induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. - Highlights: • OCA pretreatment activates hepatic FXR. • FXR activation protects against CCl 4 -induced acute liver injury. • FXR activation inhibits hepatocyte apoptosis during CCl 4 -induced liver injury. • FXR activation differentially regulates hepatic inflammatory genes. • Synthetic FXR agonists are effective antidotes for acute liver injury.

Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation

Energy Technology Data Exchange (ETDEWEB)

Zhang, Da-Gang [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Cheng [Department of Toxicology, Anhui Medical University, Hefei 230032 (China); Wang, Jun-Xian [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Wang, Bi-Wei; Wang, Hua; Zhang, Zhi-Hui; Chen, Yuan-Hua [Department of Toxicology, Anhui Medical University, Hefei 230032 (China); Lu, Yan; Tao, Li; Wang, Jian-Qing [Second Affiliated Hospital, Anhui Medical University, Hefei 230601 (China); Chen, Xi [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Xu, De-Xiang, E-mail: xudex@126.com [Department of Toxicology, Anhui Medical University, Hefei 230032 (China)

2017-01-01

The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl{sub 4})-induced acute liver injury. Mice were intraperitoneally injected with CCl{sub 4} (0.15 ml/kg). In CCl{sub 4} + OCA group, mice were orally with OCA (5 mg/kg) 48, 24 and 1 h before CCl{sub 4}. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl{sub 4}-induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited CCl{sub 4}-induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl{sub 4}-induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl{sub 4}-induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl{sub 4}-induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl{sub 4}-induced acute liver injury. These results suggest that OCA protects against CCl{sub 4}-induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. - Highlights: • OCA pretreatment activates hepatic FXR. • FXR activation protects against CCl{sub 4}-induced acute liver injury. • FXR activation inhibits hepatocyte apoptosis during CCl{sub 4}-induced liver injury. • FXR activation differentially regulates hepatic inflammatory genes. • Synthetic FXR agonists are effective antidotes for acute liver injury.

Low-grade inflammation decreases emotion recognition - Evidence from the vaccination model of inflammation.

Science.gov (United States)

Balter, Leonie J T; Hulsken, Sasha; Aldred, Sarah; Drayson, Mark T; Higgs, Suzanne; Veldhuijzen van Zanten, Jet J C S; Raymond, Jane E; Bosch, Jos A

2018-05-06

The ability to adequately interpret the mental state of another person is key to complex human social interaction. Recent evidence suggests that this ability, considered a hallmark of 'theory of mind' (ToM), becomes impaired by inflammation. However, extant supportive empirical evidence is based on experiments that induce not only inflammation but also induce discomfort and sickness, factors that could also account for temporary social impairment. Hence, an experimental inflammation manipulation was applied that avoided this confound, isolating effects of inflammation and social interaction. Forty healthy male participants (mean age = 25, SD = 5 years) participated in this double-blind placebo-controlled crossover trial. Inflammation was induced using Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur, UK); saline-injection was used as a control. About 6 h 30 m after injection in each condition, participants completed the Reading the Mind in the Eyes Test (RMET), a validated test for assessing how well the mental states of others can be inferred through observation of the eyes region of the face. Vaccination induced systemic inflammation, elevating IL-6 by +419% (p  .21). Importantly, compared to placebo, vaccination significantly reduced RMET accuracy (p valence (positive, negative, neutral) provided no evidence of a selective impact of treatment. By utilizing an inflammation-induction procedure that avoided concurrent sicknesses or symptoms in a double-blinded design, the present study provides further support for the hypothesis that immune activation impairs ToM. Such impairment may provide a mechanistic link explaining social-cognitive deficits in psychopathologies that exhibit low-grade inflammation, such as major depression. Copyright © 2018 Elsevier Inc. All rights reserved.

Nitrogen implantation of steels: A treatment which can initiate sustained oxidative wear

International Nuclear Information System (INIS)

Hale, E.B.; Reinbold, R.; Missouri Univ., Rolla; Kohser, R.A.

1987-01-01

Falex wear tests on mild (SAE 3135) steel samples treated by either nitrogen implantation (2.5x10 17 N 2 + cm -2 at 180 keV) or low temperature (about 315 0 C) oxidation are reported. The results show that both treatments lead to about an order-of-magnitude reduction in the long-term wear rate of the steel. In addition to the wear rate measurements, the wear member asymmetry behavior, scanning electron microscopy studies, Auger spectra and sputter profiles all indicate that the wear modes induced by both treatments are the same and are oxidative wear. These results confirm the previously proposed initiator-sustainer wear model in which implanted nitrogen simply acts as an initiator of favorable oxidative wear but is not directly involved in maintaining the sustained wear resistance. Possible mechanisms for both the initiation process and the sustained wear process are reviewed and discussed. (orig.)

Fretting wear of Inconel 625 at high temperature and in high vacuum

International Nuclear Information System (INIS)

Iwabuchi, A.

1985-01-01

The purpose of this work was to investigate the fretting properties of Inconel 625 at high temperature and in high vacuum. Experiments were carried out under constant conditions with a normal load of 14 N and a peak-to-peak slip amplitude of 110 μm and through 6x10 4 cycles. Several environmental conditions were used. Pressure was varied between 10 -3 and 10 5 Pa at temperatures of 20 and 500 0 C. Temperatures up to 500 0 C were also used at pressures of 10 -3 and 10 5 Pa. At 10 -3 Pa and 500 0 C wear loss was negligible but wear scars showed severe damage consisting of deep cracks and accretion of transferred debris. The coefficient of friction then maintained a high value of 1.7 throughout the fretting test. The critical pressure below which oxidation rate becomes reduced is 10 Pa, a value independent of temperature. At pressures below this critical value the coefficient of friction increases steeply and the fretting mechanism changes from one of oxidative wear to one of adhesive wear. A compacted so-called 'glaze' oxide was formed at temperatures above 300 0 C in air (10 5 Pa) and at pressures above 10 3 Pa at 500 0 C. A comparison of results for Inconel 625 with those for S45C and SUS304 steels and Inconel 600 is given. (orig.)

miR-203a is involved in HBx-induced inflammation by targeting Rap1a

Energy Technology Data Exchange (ETDEWEB)

Wu, AiRong [Department of gastroenterology, The First affiliated Hospital of Soochow University, Suzhou 215006 (China); Chen, Huo [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123 (China); Xu, ChunFang [Department of gastroenterology, The First affiliated Hospital of Soochow University, Suzhou 215006 (China); Zhou, Ji; Chen, Si [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123 (China); Shi, YuQi [Department of gastroenterology, The First affiliated Hospital of Soochow University, Suzhou 215006 (China); Xu, Jie [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123 (China); Gan, JianHe, E-mail: j_pzhang@suda.edu.cn [Department of gastroenterology, The First affiliated Hospital of Soochow University, Suzhou 215006 (China); Zhang, JinPing, E-mail: ganjianhe@aliyun.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123 (China)

2016-11-15

Hepatitis B virus (HBV) causes acute and chronic hepatitis, and is one of the major causes of cirrhosis and hepatocellular carcinoma. Accumulating evidence suggests that inflammation is the key factor for liver cirrhosis and hepatocellular carcinoma. MicroRNAs play important roles in many biological processes. Here, we aim to explore the function of microRNAs in the HBX-induced inflammation. First, microarray experiment showed that HBV{sup +} liver samples expressed higher level of miR-203a compared to HBV{sup -} liver samples. To verify these alterations, HBx-coding plasmid was transfected into HepG2 cells to overexpress HBx protein. The real-time PCR results suggested that over-expression of HBx could induce up-regulation of miR-203a. To define how up-regulation of miR-203a can induce liver cells inflammation, we over-expressed miR-203a in HepG2 cells. Annexin V staining and BrdU staining suggested that overexpression of miR-203a significantly increased the cell apoptosis and proliferation, meanwhile, over-expression of miR-203a could lead to a decrease in G0/G1 phase cells and an increase in G2/M phase cells. Some cytokines production including IL-6 and IL-8 were significantly increased, but TGFβ and IFNγ were decreased in miR-203a over-expressed HepG2 cells. Luciferase reporter assay experiments, protein mass-spectrum assay and real-time PCR all together demonstrated that Rap1a was the target gene of miR-203a. Further experiments showed that these alterations were modulated through PI3K/ERK/p38/NFκB pathways. These data suggested that HBV-infection could up-regulate the expression of miR-203a, thus down regulated the expression of Rap1a and affected the PI3K/ERK/p38/NFκB pathways, finally induced the hepatitis inflammation. - Highlights: • HBX induces the over-expression of miR-203a in HepG2 cells. • miR-203a targets Rap1a to induce the inflammation in HepG2 cells. • miR-203a regulates the apoptosis and cell cycles of HepG2 cells. • miR-203a alters

An in vitro comparison of apically extruded debris using three rotary nickel-titanium instruments

Directory of Open Access Journals (Sweden)

Tamer Tasdemir

2010-09-01

Conclusion: According to this study, all instrumentation techniques apically extruded debris through the apical foramen. However, the BioRaCe instruments induced less extruded debris than the ProTaper Universal and Mtwo rotary systems.

Design specifications to ensure flow-induced vibration and fretting-wear performance in CANDU steam generators and heat exchangers

International Nuclear Information System (INIS)

Janzen, V.P.; Han, Y.; Pettigrew, M.J.

2009-01-01

Preventing flow-induced vibration and fretting-wear problems in steam generators and heat exchangers requires design specifications that bring together specific guidelines, analysis methods, requirements and appropriate performance criteria. This paper outlines the steps required to generate and support such design specifications for CANDU nuclear steam generators and heat exchangers, and relates them to typical steam-generator design features and computer modeling capabilities. It also describes current issues that are driving changes to flow-induced vibration and fretting-wear specifications that can be applied to the design process for component refurbishment, replacement or new designs. These issues include recent experimental or field evidence for new excitation mechanisms, e.g., the possibility of in-plane fluidelastic instability of U-tubes, the demand for longer reactor and component lifetimes, the need for better predictions of dynamic properties and vibration response, e.g., two-phase random-turbulence excitation, and requirements to consider system 'excursions' or abnormal scenarios, e.g., a main steam line break in the case of steam generators. The paper describes steps being taken to resolve these issues. (author)

Can Wet Rocky Granular Flows Become Debris Flows Due to Fine Sediment Production by Abrasion?

Science.gov (United States)

Arabnia, O.; Sklar, L. S.; Bianchi, G.; Mclaughlin, M. K.

2015-12-01

Debris flows are rapid mass movements in which elevated pore pressures are sustained by a viscous fluid matrix with high concentrations of fine sediments. Debris flows may form from coarse-grained wet granular flows as fine sediments are entrained from hillslope and channel material. Here we investigate whether abrasion of the rocks within a granular flow can produce sufficient fine sediments to create debris flows. To test this hypothesis experimentally, we used a set of 4 rotating drums ranging from 0.2 to 4.0 m diameter. Each drum has vanes along the boundary ensure shearing within the flow. Shear rate was varied by changing drum rotational velocity to maintain a constant Froude Number across drums. Initial runs used angular clasts of granodiorite with a tensile strength of 7.6 MPa, with well-sorted coarse particle size distributions linearly scaled with drum radius. The fluid was initially clear water, which rapidly acquired fine-grained wear products. After each 250 m tangential distance, we measured the particle size distributions, and then returned all water and sediment to the drums for subsequent runs. We calculate particle wear rates using statistics of size and mass distributions, and by fitting the Sternberg equation to the rate of mass loss from the size fraction > 2mm. Abundant fine sediments were produced in the experiments, but very little change in the median grain size was detected. This appears to be due to clast rounding, as evidenced by a decrease in the number of stable equilibrium resting points. We find that the growth in the fine sediment concentration in the fluid scales with unit drum power. This relationship can be used to estimate fine sediment production rates in the field. We explore this approach at Inyo Creek, a steep catchment in the Sierra Nevada, California. There, a significant debris flow occurred in July 2013, which originated as a coarse-grained wet granular flow. We use surveys to estimate flow depth and velocity where super

The "Big Bang" in obese fat: Events initiating obesity-induced adipose tissue inflammation.

Science.gov (United States)

Wensveen, Felix M; Valentić, Sonja; Šestan, Marko; Turk Wensveen, Tamara; Polić, Bojan

2015-09-01

Obesity is associated with the accumulation of pro-inflammatory cells in visceral adipose tissue (VAT), which is an important underlying cause of insulin resistance and progression to diabetes mellitus type 2 (DM2). Although the role of pro-inflammatory cytokines in disease development is established, the initiating events leading to immune cell activation remain elusive. Lean adipose tissue is predominantly populated with regulatory cells, such as eosinophils and type 2 innate lymphocytes. These cells maintain tissue homeostasis through the excretion of type 2 cytokines, such as IL-4, IL-5, and IL-13, which keep adipose tissue macrophages (ATMs) in an anti-inflammatory, M2-like state. Diet-induced obesity is associated with the loss of tissue homeostasis and development of type 1 inflammatory responses in VAT, characterized by IFN-γ. A key event is a shift of ATMs toward an M1 phenotype. Recent studies show that obesity-induced adipocyte hypertrophy results in upregulated surface expression of stress markers. Adipose stress is detected by local sentinels, such as NK cells and CD8(+) T cells, which produce IFN-γ, driving M1 ATM polarization. A rapid accumulation of pro-inflammatory cells in VAT follows, leading to inflammation. In this review, we provide an overview of events leading to adipose tissue inflammation, with a special focus on adipose homeostasis and the obesity-induced loss of homeostasis which marks the initiation of VAT inflammation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Time course of polyhexamethyleneguanidine phosphate-induced lung inflammation and fibrosis in mice.

Science.gov (United States)

Song, Jeongah; Kim, Woojin; Kim, Yong-Bum; Kim, Bumseok; Lee, Kyuhong

2018-04-15

Pulmonary fibrosis is a chronic progressive disease with unknown etiology and has poor prognosis. Polyhexamethyleneguanidine phosphate (PHMG-P) causes acute interstitial pneumonia and pulmonary fibrosis in humans when it exposed to the lung. In a previous study, when rats were exposed to PHMG-P through inhalation for 3 weeks, lung inflammation and fibrosis was observed even after 3 weeks of recovery. In this study, we aimed to determine the time course of PHMG-P-induced lung inflammation and fibrosis. We compared pathological action of PHMG-P with that of bleomycin (BLM) and investigated the mechanism underlying PHMG-P-induced lung inflammation and fibrosis. PHMG-P (0.9 mg/kg) or BLM (1.5 mg/kg) was intratracheally administered to mice. At weeks 1, 2, 4 and 10 after instillation, the levels of inflammatory and fibrotic markers and the expression of inflammasome proteins were measured. The inflammatory and fibrotic responses were upregulated until 10 and 4 weeks in the PHMG-P and BLM groups, respectively. Immune cell infiltration and considerable collagen deposition in the peribronchiolar and interstitial areas of the lungs, fibroblast proliferation, and hyperplasia of type II epithelial cells were observed. NALP3 inflammasome activation was detected in the PHMG-P group until 4 weeks, which is suspected to be the main reason for the persistent inflammatory response and exacerbation of fibrotic changes. Most importantly, the pathological changes in the PHMG-P group were similar to those observed in humidifier disinfectant-associated patients. A single exposure of PHMG-P led to persistent pulmonary inflammation and fibrosis for at least 10 weeks. Copyright © 2018. Published by Elsevier Inc.

Inhibition of NF-κB Expression and Allergen-induced Airway Inflammation in a Mouse Allergic Asthma Model by Andrographolide

OpenAIRE

Li, Jing; Luo, Li; Wang, Xiaoyun; Liao, Bin; Li, Guoping

2009-01-01

Andrographolide from traditional Chinese herbal medicines previously showed it possesses a strong anti-inflammatory activity. In present study, we investigated whether Andrographolide could inhibit allergen-induced airway inflammation and airways hyper-responsiveness and explored the mechanism of Andrographolide on allergen-induced airway inflammation and airways hyper-responsiveness. After sensitized and challenged by ovalbumin, the BALB/c mice were administered intraperitoneally with Androg...

LPS-induced systemic inflammation is more severe in P2Y12 null mice.

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Liverani, Elisabetta; Rico, Mario C; Yaratha, Laxmikausthubha; Tsygankov, Alexander Y; Kilpatrick, Laurie E; Kunapuli, Satya P

2014-02-01

Thienopyridines are a class of antiplatelet drugs that are metabolized in the liver to several metabolites, of which only one active metabolite can irreversibly antagonize the platelet P2Y12 receptor. Possible effects of these drugs and the role of activated platelets in inflammatory responses have also been investigated in a variety of animal models, demonstrating that thienopyridines could alter inflammation. However, it is not clear whether it is caused only by the P2Y12 antagonism or whether off-target effects of other metabolites also intervene. To address this question, we investigated P2Y12 KO mice during a LPS-induced model of systemic inflammation, and we treated these KO mice with a thienopyridine drug (clopidogrel). Contrary to the reported effects of clopidogrel, numbers of circulating WBCs and plasma levels of cytokines were increased in LPS-exposed KO mice compared with WT in this inflammation model. Moreover, both spleen and bone marrow show an increase in cell content, suggesting a role for P2Y12 in regulation of bone marrow and spleen cellular composition. Finally, the injury was more severe in the lungs of KO mice compared with WT. Interestingly, clopidogrel treatments also exerted protective effects in KO mice, suggesting off-target effects for this drug. In conclusion, the P2Y12 receptor plays an important role during LPS-induced inflammation, and this signaling pathway may be involved in regulating cell content in spleen and bone marrow during LPS systemic inflammation. Furthermore, clopidogrel may have effects that are independent of P2Y12 receptor blockade.

Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance

Science.gov (United States)

Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammat...

Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice.

Science.gov (United States)

Wood, Tyler T; Winden, Duane R; Marlor, Derek R; Wright, Alex J; Jones, Cameron M; Chavarria, Michael; Rogers, Geraldine D; Reynolds, Paul R

2014-11-15

The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in proinflammatory signaling, and its role in irreversible pulmonary remodeling. The current research evaluated the in vivo effects of short-term secondhand smoke (SHS) exposure in RAGE knockout and control mice compared with identical animals exposed to room air only. Quantitative PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after 4 wk of SHS exposure and an anticipated absence of RAGE expression in RAGE knockout mice regardless of smoke exposure. Ras activation, NF-κB activity, and cytokine elaboration were assessed to characterize the molecular basis of SHS-induced inflammation in the mouse lung. Furthermore, bronchoalveolar lavage fluid was procured from RAGE knockout and control animals for the assessment of inflammatory cells and molecules. As a general theme, inflammation coincident with leukocyte recruitment was induced by SHS exposure and significantly influenced by the availability of RAGE. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to SHS. However, ongoing research is still warranted to fully explain roles for RAGE and other receptors in cells coping with involuntary smoke exposure for prolonged periods of time. Copyright © 2014 the American Physiological Society.

Ozone-Induced Pulmonary Injury and Inflammation are Modulated by Adrenal-Derived Stress Hormones

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Ozone exposure promotes pulmonary injury and inflammation. Previously we have characterized systemic changes that occur immediately after acute ozone exposure and are mediated by neuro-hormonal stress response pathway. Both HPA axis and sympathetic tone alterations induce the rel...

Interleukin-6 deficiency facilitates myocardial dysfunction during high fat diet-induced obesity by promoting lipotoxicity and inflammation.

Science.gov (United States)

Chen, Fan; Chen, Dandan; Zhao, Xinmei; Yang, Shuai; Li, Zhe; Sanchis, Daniel; Jin, Liang; Qiang, Xizhe; Wang, Kaiye; Xu, Yitao; Zhang, Yubin; Ye, Junmei

2017-12-01

Obesity is associated with metabolic disorder and chronic inflammation that plays a crucial role in cardiovascular diseases. IL-6 is involved in regulating obesity-related lipid metabolism and inflammation. In this study, we sought to determine the role of IL-6 in high-fat diet (HFD)-induced cardiomyopathy and explore the signaling pathway. Female, 5-week-old IL-6 knockout (KO) and littermate mice were fed a normal diet (ND, 10% fat) or HFD (45% fat) for 14 weeks. At the end of treatment, cardiac function was assessed by echocardiography. Adipose tissues and plasma were collected for further measurement. Immunohistology of CD68 was performed to detect inflammation in the heart. Masson's trichrome staining and Oil Red O staining was applied to evaluated cardiac fibrosis and lipid accumulation. Real-time PCR and Western immunoblotting analyses on heart tissue were used to explore the underlying mechanism. IL-6 KO mice displayed increased insulin resistance compared to WT mice at baseline. When fed HFD, IL-6 KO mice showed decreased gains in body weight and fat mass, increased insulin resistance relative to IL-6 KO mice feed ND. Furthermore, IL-6 KO mice developed cardiac dysfunction during HFD-induced obesity. Histological analysis suggested increased lipid accumulation, fibrosis and inflammation without affecting cardiac morphology during HFD treatment in the heart of IL-6 KO mice. Finally, IL-6 deficiency increased the phosphorylation of AMPK and ACC in the heart during HFD-induced obesity. Our results suggest that IL-6 contributes to limit lipid metabolic disorder, cardiac hypertrophy, fibrosis, inflammation and myocardium lipotoxicity during HFD-induced obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Oxidative stress induced inflammation initiates functional decline of tear production.

Directory of Open Access Journals (Sweden)

Yuichi Uchino

Full Text Available Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1 using a modified tetracycline system (Tet-On/Off system. This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b(560 large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC in humans. The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease.

In Vitro Comparison of Apically Extruded Debris during Root Canal Preparation of Mandibular Premolars with Manual and Rotary Instruments.

Science.gov (United States)

Soi, Sonal; Yadav, Suman; Sharma, Sumeet; Sharma, Mohit

2015-01-01

Background and aims. During root canal preparation, debris extruded beyond the apical foramen may result in periapical inflammation and postoperative pain. To date no root canal preparation method has been developed that extrudes no periapical debris. The purpose of this study was to identify a system leading to minimal extrusion of debris from the apical foramen. The study was conducted to comparatively evaluate the amount of apical extrusion of debris during root canal preparation using hand ProTaper and GT rotary and RaCe rotary instruments using crown-down technique. Materials and methods. Ninety freshly extracted human single-rooted mandibular premolars were equally assigned to three groups (n=30). The root canals were instrumented using hand ProTaper, GT rotary and RaCe rotary systems. Debris and irrigant extruded from the apical foramen were collected into vials. The mean weight of the remaining debris was calculated for each group and subjected to statistical analysis. Results. ANOVA was used to compare the mean dry weights of the debris extruded in the three groups, followedby post hoc Tukey tests for multiple comparisons the between groups. Highly significant differences were found in the amount of debris extruded among all the groups (PProTaper group exhibited the highest mean debris weight (0.8293±0.05433 mg) and the RaCe system exhibited the lowest mean debris weight (0.1280±0.01606 mg). Conclusion. All the systems tested resulted in apical extrusion of debris. However, the hand ProTaper files extruded a significantly higher amount of debris than GT and RaCe systems.

Fretting and wear of stainless and ferritic steels in LMFBR steam generators

International Nuclear Information System (INIS)

Lewis, M.W.J.; Campbell, C.S.

1981-01-01

Steam generators for LMFBR's may be subject to both fretting wear as a result of flow-induced vibrations and to wear from larger amplitude sliding movements from thermal changes. Results of tests simulating the latter are given for stainless and ferritic steels. For the assessment of fretting wear damage, vibration assessments must be combined with data on specific wear rates. Test mechanisms used to study fretting in sodium covering impact, impact-slide and pure rubbing are described and results presented. (author)

EDDA: integrated simulation of debris flow erosion, deposition and property changes

Science.gov (United States)

Chen, H. X.; Zhang, L. M.

2014-11-01

Debris flow material properties change during the initiation, transportation and deposition processes, which influences the runout characteristics of the debris flow. A quasi-three-dimensional depth-integrated numerical model, EDDA, is presented in this paper to simulate debris flow erosion, deposition and induced material property changes. The model considers changes in debris flow density, yield stress and dynamic viscosity during the flow process. The yield stress of debris flow mixture is determined at limit equilibrium using the Mohr-Coulomb equation, which is applicable to clear water flow, hyper-concentrated flow and fully developed debris flow. To assure numerical stability and computational efficiency at the same time, a variable time stepping algorithm is developed to solve the governing differential equations. Four numerical tests are conducted to validate the model. The first two tests involve a one-dimensional dam-break water flow and a one-dimensional debris flow with constant properties. The last two tests involve erosion and deposition, and the movement of multi-directional debris flows. The changes in debris flow mass and properties due to either erosion or deposition are shown to affect the runout characteristics significantly. The model is also applied to simulate a large-scale debris flow in Xiaojiagou Ravine to test the performance of the model in catchment-scale simulations. The results suggest that the model estimates well the volume, inundated area, and runout distance of the debris flow. The model is intended for use as a module in a real-time debris flow warning system.

Protective effect of Arbutus unedo aqueous extract in carrageenan-induced lung inflammation in mice.

Science.gov (United States)

Mariotto, Sofia; Esposito, Emanuela; Di Paola, Rosanna; Ciampa, Anna; Mazzon, Emanuela; de Prati, Alessandra Carcereri; Darra, Elena; Vincenzi, Simone; Cucinotta, Giovanni; Caminiti, Rocco; Suzuki, Hisanori; Cuzzocrea, Salvatore

2008-02-01

In the present study, we show that an aqueous extract of Arbutus unedo L. (AuE), a Mediterranean endemic plant widely employed as an astringent, diuretic and urinary anti-septic, in vitro down-regulates the expression of some inflammatory genes, such as those encoding inducible nitric oxide synthase (iNOS) and intracellular adhesion molecule-(ICAM)-1, exerting a inhibitory action on both IFN-gamma-elicited STAT1 activation and IL-6-elicited STAT3 activation. To evaluate further the effect of AuE in animal models of acute inflammation, we examined whether AuE administration attenuates inflammatory response of murine induced by intrapleural injection of carrageenan. For this purpose we studied: (1) STAT1/3 activation, (2) TNF-alpha, IL-1beta and IL-6 production in pleural exudate, (3) lung iNOS, COX-2 and ICAM-1 expression, (4) neutrophil infiltration, (5) the nitration of cellular proteins by peroxynitrite, (6) lipid peroxidation, (7) prostaglandin E2 and nitrite/nitrate levels and (8) lung injury. We show that AuE strongly down-regulates STAT3 activation induced in the lung by carrageenan with concomitant attenuation of all parameters examined associated with inflammation, suggesting that STAT3 should be a new molecular target for anti-inflammatory treatment. This study demonstrates that acute lung inflammation is significantly attenuated by the treatment with AuE.

A new methodology for predictive tool wear

Science.gov (United States)

Kim, Won-Sik

turned with various cutting conditions and the results were compared with the proposed analytical wear models. The crater surfaces after machining have been carefully studied to shed light on the physics behind the crater wear. In addition, the abrasive wear mechanism plays a major role in the development of crater wear. Laser shock processing (LSP) has been applied to locally relieve the deleterious tensile residual stresses on the crater surface of a coated tool, thus to improve the hardness of the coating. This thesis shows that LSP has indeed improve wear resistance of CVD coated alumina tool inserts, which has residual stress due to high processing temperature. LSP utilizes a very short laser pulse with high energy density, which induces high-pressure stress wave propagation. The residual stresses are relieved by incident shock waves on the coating surface. Residual stress levels of LSP CVD alumina-coated carbide insert were evaluated by the X-ray diffractometer. Based on these results, LSP parameters such as number of laser pulses and laser energy density can be controlled to reduce residual stress. Crater wear shows that the wear resistance increase with LSP treated tool inserts. Because the hardness data are used to predict the wear, the improvement in hardness and wear resistance shows that the mechanism of crater wear also involves abrasive wear.

LFG-500, a newly synthesized flavonoid, attenuates lipopolysaccharide-induced acute lung injury and inflammation in mice.

Science.gov (United States)

Li, Chenglin; Yang, Dan; Cao, Xin; Wang, Fan; Jiang, Haijing; Guo, Hao; Du, Lei; Guo, Qinglong; Yin, Xiaoxing

2016-08-01

Acute lung injury (ALI) often causes significant morbidity and mortality worldwide. Improved treatment and effective strategies are still required for ALI patients. Our previous studies demonstrated that LFG-500, a novel synthesized flavonoid, has potent anti-cancer activities, while its anti-inflammatory effect has not been revealed. In the present study, the in vivo protective effect of LFG-500 on the amelioration of lipopolysaccharide (LPS)-induced ALI and inflammation was detected. LFG-500 attenuated LPS-induced histological alterations, suppressed the infiltration of inflammatory cells in lung tissues and bronchoalveolar lavage fluid, as well as inhibited the secretion of several inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in lung tissues after LPS challenge. In addition, the in vitro effects and mechanisms were studied in LPS stimulated RAW 264.7 cells and THP-1 cells. LFG-500 significantly decreased the secretion and expression of TNF-α, IL-1β, and IL-6 through inhibiting the transcriptional activation of NF-κB. Moreover, overexpression of NF-κB p65 reversed the inhibitory effect of LFG-500 on LPS-induced NF-κB activation and inflammatory cytokine secretion. Further elucidation of the mechanism revealed that p38 and JNK MAPK pathways were involved in the anti-inflammation effect of LFG-500, through which LFG-500 inhibited the classical IKK-dependent pathway and led to inactivation of NF-κB. More importantly, LFG-500 suppressed the expression and nuclear localization of NF-κB in LPS-induced ALI mice. Taken together, these results demonstrated that LFG-500 could attenuate LPS-induced ALI and inflammation by suppressing NF-κB activation, which provides new evidence for the anti-inflammation activity of LFG-500. Copyright © 2016 Elsevier Inc. All rights reserved.

Peri-Implant Distribution of Polyethylene Debris in Postmortem-Retrieved Knee Arthroplasties: Can Polyethylene Debris Explain Loss of Cement-Bone Interlock in Successful Total Knee Arthroplasties?

Science.gov (United States)

Cyndari, Karen I; Goodheart, Jacklyn R; Miller, Mark A; Oest, Megan E; Damron, Timothy A; Mann, Kenneth A

2017-07-01

Loss of mechanical interlock between cement and bone with in vivo service has been recently quantified for functioning, nonrevised, cemented total knee arthroplasties (TKAs). The cause of interlocking trabecular resorption is not known. The goal of this study is to quantify the distribution of PE debris at the cement-bone interface and determine if polyethylene (PE) debris is locally associated with loss of interlock. Fresh, nonrevised, postmortem-retrieved TKAs (n = 8) were obtained en bloc. Laboratory-prepared constructs (n = 2) served as negative controls. The intact cement-bone interface of each proximal tibia was embedded in Spurr's resin, sectioned, and imaged under polarized light to identify birefringent PE particles. PE wear particle number density was quantified at the cement-bone interface and distal to the interface, and then compared with local loss of cement-bone interlock. The average PE particle number density for postmortem-retrieved TKAs ranged from 8.6 (1.3) to 24.9 (3.1) particles/mm 2 (standard error) but was weakly correlated with years in service. The average particle number density was twice as high as distal (>5mm) to the interface compared to at the interface. The local loss of interlock at the interface was not related to the presence, absence, or particle density of PE. PE debris can migrate extensively along the cement-bone interface of well-fixed tibial components. However, the amount of local bone loss at the cement-bone interface was not correlated with the amount of PE debris at the interface, suggesting that the observed loss of trabecular interlock in these well-fixed TKAs may be due to alternative factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Numerical investigation of debris materials prior to debris flow hazards using satellite images

Science.gov (United States)

Zhang, N.; Matsushima, T.

2018-05-01

The volume of debris flows occurred in mountainous areas is mainly affected by the volume of debris materials deposited at the valley bottom. Quantitative evaluation of debris materials prior to debris flow hazards is important to predict and prevent hazards. At midnight on 7th August 2010, two catastrophic debris flows were triggered by the torrential rain from two valleys in the northern part of Zhouqu City, NW China, resulting in 1765 fatalities and huge economic losses. In the present study, a depth-integrated particle method is adopted to simulate the debris materials, based on 2.5 m resolution satellite images. In the simulation scheme, the materials are modeled as dry granular solids, and they travel down from the slopes and are deposited at the valley bottom. The spatial distributions of the debris materials are investigated in terms of location, volume and thickness. Simulation results show good agreement with post-disaster satellite images and field observation data. Additionally, the effect of the spatial distributions of the debris materials on subsequent debris flows is also evaluated. It is found that the spatial distributions of the debris materials strongly influence affected area, runout distance and flow discharge. This study might be useful in hazard assessments prior to debris flow hazards by investigating diverse scenarios in which the debris materials are unknown.

Rac1 signaling regulates cigarette smoke-induced inflammation in the lung via the Erk1/2 MAPK and STAT3 pathways.

Science.gov (United States)

Jiang, Jun-Xia; Zhang, Shui-Juan; Shen, Hui-Juan; Guan, Yan; Liu, Qi; Zhao, Wei; Jia, Yong-Liang; Shen, Jian; Yan, Xiao-Feng; Xie, Qiang-Min

2017-07-01

Cigarette smoke (CS) is a major risk factor for the development of chronic obstructive pulmonary disease (COPD). Our previous studies have indicated that Rac1 is involved in lipopolysaccharide-induced pulmonary injury and CS-mediated epithelial-mesenchymal transition. However, the contribution of Rac1 activity to CS-induced lung inflammation remains not fully clear. In this study, we investigated the regulation of Rac1 in CS-induced pulmonary inflammation. Mice or 16HBE cells were exposed to CS or cigarette smoke extract (CSE) to induce acute inflammation. The lungs of mice exposed to CS showed an increase in the release of interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC), as well as an accumulation of inflammatory cells, indicating high Rac1 activity. The exposure of 16HBE cells to CSE resulted in elevated Rac1 levels, as well as increased release of IL-6 and interleukin-8 (IL-8). Selective inhibition of Rac1 ameliorated the release of IL-6 and KC as well as inflammation in the lungs of CS-exposed mice. Histological assessment showed that treatment with a Rac1 inhibitor, NSC23766, led to a decrease in CD68 and CD11b positive cells and the infiltration of neutrophils and macrophages into the alveolar spaces. Selective inhibition or knockdown of Rac1 decreased IL-6 and IL-8 release in 16HBE cells induced by CSE, which correlated with CSE-induced Rac1-regulated Erk1/2 mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3) signaling. Our data suggest an important role for Rac1 in the pathological alterations associated with CS-mediated inflammation. Rac1 may be a promising therapeutic target for the treatment of CS-induced pulmonary inflammation. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparing two models for post-wildfire debris flow susceptibility mapping

Science.gov (United States)

Cramer, J.; Bursik, M. I.; Legorreta Paulin, G.

2017-12-01

Traditionally, probabilistic post-fire debris flow susceptibility mapping has been performed based on the typical method of failure for debris flows/landslides, where slip occurs along a basal shear zone as a result of rainfall infiltration. Recent studies have argued that post-fire debris flows are fundamentally different in their method of initiation, which is not infiltration-driven, but surface runoff-driven. We test these competing models by comparing the accuracy of the susceptibility maps produced by each initiation method. Debris flow susceptibility maps are generated according to each initiation method for a mountainous region of Southern California that recently experienced wildfire and subsequent debris flows. A multiple logistic regression (MLR), which uses the occurrence of past debris flows and the values of environmental parameters, was used to determine the probability of future debris flow occurrence. The independent variables used in the MLR are dependent on the initiation method; for example, depth to slip plane, and shear strength of soil are relevant to the infiltration initiation, but not surface runoff. A post-fire debris flow inventory serves as the standard to compare the two susceptibility maps, and was generated by LiDAR analysis and field based ground-truthing. The amount of overlap between the true locations where debris flow erosion can be documented, and where the MLR predicts high probability of debris flow initiation was statistically quantified. The Figure of Merit in Space (FMS) was used to compare the two models, and the results of the FMS comparison suggest that surface runoff-driven initiation better explains debris flow occurrence. Wildfire can breed conditions that induce debris flows in areas that normally would not be prone to them. Because of this, nearby communities at risk may not be equipped to protect themselves against debris flows. In California, there are just a few months between wildland fire season and the wet

Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways

Directory of Open Access Journals (Sweden)

Yang Yao-Jong

2012-03-01

Full Text Available Abstract Background H. pylori infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways. Results Challenge with H. pylori increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after H. pylori infection in a dose-dependent manner. A higher dose (MOI 100 of L. acidophilus pre-treatment attenuated the H. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. L. acidophilus also inhibited H. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. L. acidophilus pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting. Conclusions H. pylori infection induces Smad7, NFκB, IL-8, and TNF-α production in vitro. Higher doses of L. acidophilus pre-treatment reduce H. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.

Inflammation-associated gene transcription and expression in mouse lungs induced by low molecular weight compounds from fungi from the built environment.

Science.gov (United States)

Miller, J D; Sun, M; Gilyan, A; Roy, J; Rand, T G

2010-01-05

Few metabolites from fungi found indoors have been tested for inflammatory mediators endpoints in primary cultures of alveolar macrophages or in vivo. In this study, mice were intratracheally instilled with a single dose comprising 4x10(-5)moletoxin/kg lung wt dose of either atranone C, brevianamide, cladosporin, mycophenolic acid, neoechinulin A & B, sterigmatocystin or TMC-120A. These toxins are from fungi common on damp building materials. The dose used was comparable to the estimated doses of possible human exposure. Hematoxylin and eosin (H&E) histology and Alcian Blue/Periodic Acid Schiff (AB/PAS) histochemistry were used to evaluate lungs for time course (4h and 12h post-exposure (PE)) inflammatory and toxic changes. Reverse-transcription (RT)-PCR based arrays were also employed to evaluate time course inflammation-associated gene transcription in lung tissues of the different toxins. Immunohistochemistry (IHC) was used to probe MIP-2 and Tnf-alpha protein expression in treatment lungs to determine whether responses correspond with gene transcription data. Both histology and histochemistry revealed that toxin exposed lungs at 12h PE showed evidence of inflammation. H&E revealed that bronchioli were lined with irregularly thickened and sometimes sloughing epithelium and bronchiolar spaces supported infiltration of leukocytes, cellular and mucus-like debris while alveolar spaces supported swollen macrophages and modest amorphous debris accumulations. All toxin-instilled lungs exhibited copious mucus production and alveolar macrophages with red stained cytoplasm on bronchiolar surfaces, especially at 12h PE. Array analysis of 83 inflammation-associated genes extracted from lung tissue demonstrated a number of patterns, compared to controls. 82 genes assayed at 4h PE and 75 genes at 12h PE were significantly altered (por =1.5-fold or cladosporin, atranone C and TMC-120. The results further confirm the inflammatory nature of metabolites/toxins from such fungi can

miR-217 regulates ethanol-induced hepatic inflammation by disrupting sirtuin 1-lipin-1 signaling.

Science.gov (United States)

Yin, Huquan; Liang, Xiaomei; Jogasuria, Alvin; Davidson, Nicholas O; You, Min

2015-05-01

Ethanol-mediated injury, combined with gut-derived lipopolysaccharide (LPS), provokes generation of proinflammatory cytokines in Kupffer cells, causing hepatic inflammation. Among the mediators of these effects, miR-217 aggravates ethanol-induced steatosis in hepatocytes. However, the role of miR-217 in ethanol-induced liver inflammation process is unknown. Here, we examined the role of miR-217 in the responses to ethanol, LPS, or a combination of ethanol and LPS in RAW 264.7 macrophages and in primary Kupffer cells. In macrophages, ethanol substantially exacerbated LPS-mediated induction of miR-217 and production of proinflammatory cytokines compared with LPS or ethanol alone. Consistently, ethanol administration to mice led to increases in miR-217 abundance and increased production of inflammatory cytokines in isolated primary Kupffer cells exposed to the combination of ethanol and LPS. miR-217 promoted combined ethanol and LPS-mediated inhibition of sirtuin 1 expression and activity in macrophages. Moreover, miR-217-mediated sirtuin 1 inhibition was accompanied by increased activities of two vital inflammatory regulators, NF-κB and the nuclear factor of activated T cells c4. Finally, adenovirus-mediated overexpression of miR-217 led to steatosis and inflammation in mice. These findings suggest that miR-217 is a pivotal regulator involved in ethanol-induced hepatic inflammation. Strategies to inhibit hepatic miR-217 could be a viable approach in attenuating alcoholic hepatitis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Macrophage migration inhibitory factor triggers chemotaxis of CD74+CXCR2+ NKT cells in chemically induced IFN-γ-mediated skin inflammation.

Science.gov (United States)

Hsieh, Chia-Yuan; Chen, Chia-Ling; Lin, Yee-Shin; Yeh, Trai-Ming; Tsai, Tsung-Ting; Hong, Ming-Yuan; Lin, Chiou-Feng

2014-10-01

IFN-γ mediates chemically induced skin inflammation; however, the mechanism by which IFN-γ-producing cells are recruited to the sites of inflammation remains undefined. Secretion of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, from damaged cells may promote immune cell recruitment. We hypothesized that MIF triggers an initial step in the chemotaxis of IFN-γ-producing cells in chemically induced skin inflammation. Using acute and chronic models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mouse ears, MIF expression was examined, and its role in this process was investigated pharmacologically. The cell populations targeted by MIF, their receptor expression patterns, and the effects of MIF on cell migration were examined. TPA directly caused cytotoxicity accompanied by MIF release in mouse ear epidermal keratinocytes, as well as in human keratinocytic HaCaT cells. Treatment with the MIF antagonist (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester considerably attenuated TPA-induced ear swelling, leukocyte infiltration, epidermal cell proliferation, and dermal angiogenesis. Inhibition of MIF greatly diminished the dermal infiltration of IFN-γ(+) NKT cells, whereas the addition of exogenous TPA and MIF to NKT cells promoted their IFN-γ production and migration, respectively. MIF specifically triggered the chemotaxis of NKT cells via CD74 and CXCR2, and the resulting depletion of NKT cells abolished TPA-induced skin inflammation. In TPA-induced skin inflammation, MIF is released from damaged keratinocytes and then triggers the chemotaxis of CD74(+)CXCR2(+) NKT cells for IFN-γ production. Copyright © 2014 by The American Association of Immunologists, Inc.

15-lipoxygenase metabolites play an important role in the development of a T-helper type 1 allergic inflammation induced by double-stranded RNA.

Science.gov (United States)

Jeon, S G; Moon, H-G; Kim, Y-S; Choi, J-P; Shin, T-S; Hong, S-W; Tae, Y-M; Kim, S-H; Zhu, Z; Gho, Y S; Kim, Y-K

2009-06-01

We recently demonstrated that the T-helper type 1 (Th1) immune response plays an important role in the development of non-eosinophilic inflammation induced by airway exposure of an allergen plus double-stranded RNA (dsRNA). However, the role of lipoxygenase (LO) metabolites in the development of Th1 inflammation is poorly understood. To evaluate the role of LO metabolites in the development of Th1 inflammation induced by sensitization with an allergen plus dsRNA. A Th2-allergic inflammation mouse model was created by an intraperitoneal injection of lipopolysaccharide-depleted ovalbumin (OVA, 75 microg) and alum (2 mg) twice, and the Th1 model was created by intranasal application of OVA (75 microg) and synthetic dsRNA [10 microg of poly(I : C)] four times, followed by an intranasal challenge with 50 microg of OVA four times. The role of LO metabolites was evaluated using two approaches: a transgenic approach using 5-LO(-/-) and 15-LO(-/-) mice, and a pharmacological approach using inhibitors of cysteinyl leucotriene receptor-1 (cysLTR1), LTB4 receptor (BLT1), and 15-LO. We found that the Th1-allergic inflammation induced by OVA+dsRNA sensitization was similar between 5-LO(-/-) and wild-type (WT) control mice, although Th2 inflammation induced by sensitization with OVA+alum was reduced in the former group. In addition, dsRNA-induced Th1 allergic inflammation, which is associated with down-regulation of 15-hydroxyeicosateraenoic acids production, was not affected by treatment with cysLTR1 or BLT1 inhibitors, whereas it was significantly lower in 12/15-LO(-/-) mice compared with WT control mice. Moreover, dsRNA-induced allergic inflammation and the recruitment of T cells following an allergen challenge were significantly inhibited by treatment with a specific 15-LO inhibitor (PD146176). 15-LO metabolites appear to be important mediators in the development of Th1-allergic inflammation induced by sensitization with an allergen plus dsRNA. Our findings suggest that the

Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.

Science.gov (United States)

Kida, Taiki; Ayabe, Shinya; Omori, Keisuke; Nakamura, Tatsuro; Maehara, Toko; Aritake, Kosuke; Urade, Yoshihiro; Murata, Takahisa

2016-01-01

Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis.

Fire debris analysis for forensic fire investigation using laser induced breakdown spectroscopy (LIBS)

Science.gov (United States)

Choi, Soojin; Yoh, Jack J.

2017-08-01

The possibility verification of the first attempt to apply LIBS to arson investigation was performed. LIBS has capabilities for real time in-situ analysis and depth profiling. It can provide valuable information about the fire debris that are complementary to the classification of original sample components and combustion residues. In this study, fire debris was analyzed to determine the ignition source and existence of a fire accelerant using LIBS spectra and depth profiling analysis. Fire debris chemical composition and carbon layer thickness determines the possible ignition source while the carbon layer thickness of combusted samples represents the degree of sample carbonization. When a sample is combusted with fire accelerants, a thicker carbon layer is formed because the burning rate is increased. Therefore, depth profiling can confirm the existence of combustion accelerants, which is evidence of arson. Also investigation of fire debris by depth profiling is still possible when a fire is extinguished with water from fire hose. Such data analysis and in-situ detection of forensic signals via the LIBS may assist fire investigation at crime scenes.

An advanced tube wear and fatigue workstation to predict flow induced vibrations of steam generator tubes

International Nuclear Information System (INIS)

Gay, N.; Baratte, C.; Flesch, B.

1997-01-01

Flow induced tube vibration damage is a major concern for designers and operators of nuclear power plant steam generators (SG). The operating flow-induced vibrational behaviour has to be estimated accurately to allow a precise evaluation of the new safety margins in order to optimize the maintenance policy. For this purpose, an industrial 'Tube Wear and Fatigue Workstation', called 'GEVIBUS Workstation' and based on an advanced methodology for predictive analysis of flow-induced vibration of tube bundles subject to cross-flow has been developed at Electricite de France. The GEVIBUS Workstation is an interactive processor linking modules as: thermalhydraulic computation, parametric finite element builder, interface between finite element model, thermalhydraulic code and vibratory response computations, refining modelling of fluid-elastic and random forces, linear and non-linear dynamic response and the coupled fluid-structure system, evaluation of tube damage due to fatigue and wear, graphical outputs. Two practical applications are also presented in the paper; the first simulation refers to an experimental set-up consisting of a straight tube bundle subject to water cross-flow, while the second one deals with an industrial configuration which has been observed in some operating steam generators i.e., top tube support plate degradation. In the first case the GEVIBUS predictions in terms of tube displacement time histories and phase planes have been found in very good agreement with experiment. In the second application the GEVIBUS computation showed that a tube with localized degradation is much more stable than a tube located in an extended degradation zone. Important conclusions are also drawn concerning maintenance. (author)

Dynamic Characteristics of Steam Generator Tubes with Defect due to Wear

Energy Technology Data Exchange (ETDEWEB)

Park, Sangjin; Rhee, Huinam [Sunchon National Univ., Sunchon (Korea, Republic of); Yoon, Doo Byung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-05-15

These defects may affect the dynamic characteristics of tubes, and therefore, the vibrational behavior of the tube due to flow-induced loads can be varied. Change in the vibrational response of a tube may result in different wear characteristics from the design condition, which must be checked for both safety and economic point of view. This paper deals with the study on the effect of wears or cracks on the dynamic characteristics of steam generator tubes using finite element analysis. In this paper the effect of defects on the surface due to wear on the variation of dynamic characteristics of steam generator tubes was studied using the finite element analysis. The changes of natural frequencies and mode shapes can directly affect the flow-induced vibration response characteristics, therefore, they must be evaluated appropriately. The results in this study can be a good basis to estimate the FIV characteristics of the steam generator tubes having defects such as wear or crack.

Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation

Energy Technology Data Exchange (ETDEWEB)

Li, Zheng Jun; Shin, Jung-Min; Choi, Dae-Kyoung; Lim, Seul Ki [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Yoon, Tae-Jin [Department of Dermatology, School of Medicine, Gyeongsang National University, Jinju (Korea, Republic of); Lee, Young Ho [Department of Anatomy, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Sohn, Kyung-Cheol; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Lee, Jeung-Hoon, E-mail: jhoon@cnu.ac.kr [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Skin Med Company, Daejeon (Korea, Republic of)

2015-04-17

Psoriasis is a common skin disease, of which pathogenesis involves the increase of inflammatory reaction in epidermal cells. In an attempt to find therapeutics for psoriasis, we found that cucurbitacin B has an inhibitory potential on imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL-8 and CCL20, via down-regulation of NF-κB and STAT3 signaling pathway in human keratinocytes. In addition, keratinocyte proliferation was markedly inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of experimental animal. Topical application of cucurbitacin B resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines production, and ameliorated the psoriatic symptom. Taken together, these results suggest that cucurbitacin B may be a potential candidate for the treatment of psoriasis. - Highlights: • Cucurbitacin B has a potential for inhibiting the growth of keratinocytes. • Cucurbitacin B inhibits imiquimod-induced inflammatory reaction in keratinocytes. • Cucurbitacin B inhibits imiquimod-induced psoriasiform dermatitis in experimental animal.

Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation

International Nuclear Information System (INIS)

Li, Zheng Jun; Shin, Jung-Min; Choi, Dae-Kyoung; Lim, Seul Ki; Yoon, Tae-Jin; Lee, Young Ho; Sohn, Kyung-Cheol; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok; Lee, Jeung-Hoon

2015-01-01

Psoriasis is a common skin disease, of which pathogenesis involves the increase of inflammatory reaction in epidermal cells. In an attempt to find therapeutics for psoriasis, we found that cucurbitacin B has an inhibitory potential on imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL-8 and CCL20, via down-regulation of NF-κB and STAT3 signaling pathway in human keratinocytes. In addition, keratinocyte proliferation was markedly inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of experimental animal. Topical application of cucurbitacin B resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines production, and ameliorated the psoriatic symptom. Taken together, these results suggest that cucurbitacin B may be a potential candidate for the treatment of psoriasis. - Highlights: • Cucurbitacin B has a potential for inhibiting the growth of keratinocytes. • Cucurbitacin B inhibits imiquimod-induced inflammatory reaction in keratinocytes. • Cucurbitacin B inhibits imiquimod-induced psoriasiform dermatitis in experimental animal

The role of the arachidonic acid cascade in the species-specific X-ray-induced inflammation of the rabbit eye

International Nuclear Information System (INIS)

Bito, L.Z.; Klein, E.M.

1982-01-01

To identify the mediator(s) of the apparently species-specific X-ray-induced inflammation of the rabbit eye, inhibitors of the synthesis and/or release of known or putative mediators of ocular inflammation were administered prior to irradiation. The X-ray-induced ocular inflammation, particularly the rise in intraocular pressure, was found to be inhibited by intravenous pretreatment of rabbits with flurbiprofen, indomethacin, or imidazole (1, 10, and 100 mg/kg i.v., respectively), or by combined intravitreal and topical administration of flurbiprofen. Systemic, intravitreal, and/or topical pretreatment with prednisolone or disodium cromoglycate or the retrobulbar injection of ethyl alcohol or capsaicin failed to block the inflammatory response, whereas vitamin E apparently exerted some protective effect. These findings show that the X-ray-induced inflammation of the rabbit eye is mediated, at least in part, by prostaglandins (PGs) and/or related autacoids. In addition, these results suggest that the unique sensitivity of the rabbit eye to X-ray-induced inflammation is due either to the presence in this species of a unique or uniquely effective triggering mechanism for the release of PG precursors or to the greater sensitivity of this species to the ocular inflammatory effects of PGs. Thus the rabbit eye may provide a unique model for studying some aspects of arachidonic acid release or ocular PG effects, but extreme caution must be exercised in generalizing such findings to other species

Systemic N-terminal fragments of adrenocorticotropin reduce inflammation- and stress-induced anhedonia in rats.

Science.gov (United States)

Markov, Dmitrii D; Yatsenko, Ksenia A; Inozemtseva, Lyudmila S; Grivennikov, Igor A; Myasoedov, Nikolai F; Dolotov, Oleg V

2017-08-01

Emerging evidence implicates impaired self-regulation of the hypothalamic-pituitary-adrenal (HPA) axis and inflammation as important and closely related components of the pathophysiology of major depression. Antidepressants show anti-inflammatory effects and are suggested to enhance glucocorticoid feedback inhibition of the HPA axis. HPA axis activity is also negatively self-regulated by the adrenocorticotropic hormone (ACTH), a potent anti-inflammatory peptide activating five subtypes of melanocortin receptors (MCRs). There are indications that ACTH-mediated feedback can be activated by noncorticotropic N-terminal ACTH fragments such as a potent anti-inflammatory MC1/3/4/5R agonist α-melanocyte-stimulating hormone (α-MSH), corresponding to ACTH(1-13), and a MC3/5R agonist ACTH(4-10). We investigated whether intraperitoneal administration of rats with these peptides affects anhedonia, which is a core symptom of depression. Inflammation-related anhedonia was induced by a single intraperitoneal administration of a low dose (0.025mg/kg) of lipopolysaccharide (LPS). Stress-related anhedonia was induced by the chronic unpredictable stress (CUS) procedure. The sucrose preference test was used to detect anhedonia. We found that ACTH(4-10) pretreatment decreased LPS-induced increase in serum corticosterone and tumor necrosis factor (TNF)-α, and a MC3/4R antagonist SHU9119 blocked this effect. Both α-MSH and ACTH(4-10) alleviated LPS-induced anhedonia. In the CUS model, these peptides reduced anhedonia and normalized body weight gain. The data indicate that systemic α-MSH and ACTH(4-10) produce an antidepressant-like effect on anhedonia induced by stress or inflammation, the stimuli that trigger the release of ACTH and α-MSH into the bloodstream. The results suggest a counterbalancing role of circulating melanocortins in depression and point to a new approach for antidepressant treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Invariant Natural Killer T Cells Ameliorate Monosodium Urate Crystal-Induced Gouty Inflammation in Mice

Directory of Open Access Journals (Sweden)

Jie Wang

2017-12-01

Full Text Available Gout is an inflammatory arthritis caused by deposition of intra-articular monosodium urate (MSU crystal. Previous studies have focused on resident macrophage, infiltrating monocyte, and neutrophil responses to MSU crystal; yet the mechanisms of cellular changes and the potential involvement of other regulatory immune cells remain largely unknown. Invariant natural killer T (iNKT cells, an innate type of T cell, are involved in the development of various inflammatory diseases. Here, we investigate the role of iNKT cells in MSU crystal-induced gouty inflammation. MSU crystal-induced inflammatory profiles in an air-pouch model were examined in iNKT-deficient CD1d knockout (KO and wild-type (WT control mice. To explore potential mechanisms of iNKT cell regulation of gouty inflammation, we cocultured CD4+ or CD4−iNKT cells with bone marrow-derived macrophages (BMDMs. We found that iNKT cells quickly migrated to the site of inflammation upon MSU crystal stimulation in WT mice. The total number of infiltrating cells in CD1d KO mice, especially neutrophils, was dramatically increased at 6 and 12 h (P < 0.01 post-MSU crystal challenge, compared with WT controls. BMDMs cocultured with CD4+iNKT cells produced less tumor necrosis factor-α and expressed higher levels of M2 macrophage markers, including Clec7a, Pdcd1Ig2, and interleukin-4 (P < 0.01, compared with BMDMs cocultured with CD4−iNKT cells or conventional CD4+ T cells. CD4+iNKT cells are one of the key regulators of MSU crystal-induced gouty inflammation through the control of macrophage polarization. iNKT cells may serve as a new therapeutic target for gout.

Effect of photon-initiated photoacoustic streaming on removal of apically placed dentinal debris.

Science.gov (United States)

Arslan, H; Capar, I D; Saygili, G; Gok, T; Akcay, M

2014-11-01

To compare the efficacy of photon-induced photoacoustic streaming (PIPS) technique with conventional, sonic and ultrasonic irrigation on the removal of apically placed dentinal debris from an artificial groove created in a root canal. Root canal preparation was performed up to size 40 on 48 extracted single-rooted teeth using ProTaper rotary instruments. The specimens were then split longitudinally, and a standardized groove was prepared in the apical part of each segment. Each groove was filled with dentinal debris mixed with 5% NaOCl. Each tooth was reassembled and irrigated as follows: (i) conventional irrigation with 1% NaOCl, (ii) sonic, (iii) ultrasonic irrigation, and (iv) PIPS. The root segments were disassembled, and the amount of remaining dentinal debris was evaluated under a stereomicroscope at 20× magnification, using a four-grade scoring system. The data were evaluated statistically using Kruskal-Wallis and Mann-Whitney U-tests with a 95% confidence level (P = 0.05). Photon-induced photoacoustic streaming removed significantly more dentinal debris than conventional irrigation (P streaming was more effective than conventional, sonic and ultrasonic irrigation in the removal of apically placed dentinal debris. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Cobalt-alloy implant debris induce HIF-1α hypoxia associated responses: a mechanism for metal-specific orthopedic implant failure.

Directory of Open Access Journals (Sweden)

Lauryn Samelko

Full Text Available The historical success of orthopedic implants has been recently tempered by unexpected pathologies and early failures of some types of Cobalt-Chromium-Molybdenum alloy containing artificial hip implants. Hypoxia-associated responses to Cobalt-alloy metal debris were suspected as mediating this untoward reactivity at least in part. Hypoxia Inducible Factor-1α is a major transcription factor involved in hypoxia, and is a potent coping mechanism for cells to rapidly respond to changing metabolic demands. We measured signature hypoxia associated responses (i.e. HIF-1α, VEGF and TNF-α to Cobalt-alloy implant debris both in vitro (using a human THP-1 macrophage cell line and primary human monocytes/macrophages and in vivo. HIF-1α in peri-implant tissues of failed metal-on-metal implants were compared to similar tissues from people with metal-on-polymer hip arthroplasties, immunohistochemically. Increasing concentrations of cobalt ions significantly up-regulated HIF-1α with a maximal response at 0.3 mM. Cobalt-alloy particles (1 um-diameter, 10 particles/cell induced significantly elevated HIF-1α, VEGF, TNF-α and ROS expression in human primary macrophages whereas Titanium-alloy particles did not. Elevated expression of HIF-1α was found in peri-implant tissues and synovial fluid of people with failing Metal-on-Metal hips (n = 5 compared to failed Metal-on-Polymer articulating hip arthroplasties (n = 10. This evidence suggests that Cobalt-alloy, more than other metal implant debris (e.g. Titanium alloy, can elicit hypoxia-like responses that if unchecked can lead to unusual peri-implant pathologies, such as lymphocyte infiltration, necrosis and excessive fibrous tissue growths.

In Vitro Comparison of Apically Extruded Debris during Root Canal Preparation of Mandibular Premolars with Manual and Rotary Instruments

Directory of Open Access Journals (Sweden)

Sonal Soi

2015-09-01

Full Text Available Background and aims. During root canal preparation, debris extruded beyond the apical foramen may result in periapical inflammation and postoperative pain. To date no root canal preparation method has been developed that extrudes no peri-apical debris. The purpose of this study was to identify a system leading to minimal extrusion of debris from the apical fo-ramen. The study was conducted to comparatively evaluate the amount of apical extrusion of debris during root canal prepa-ration using hand ProTaper and GT rotary and RaCe rotary instruments using crown-down technique. Materials and methods. Ninety freshly extracted human single-rooted mandibular premolars were equally assigned to three groups (n=30. The root canals were instrumented using hand ProTaper, GT rotary and RaCe rotary systems. Debris and irrigant extruded from the apical foramen were collected into vials. The mean weight of the remaining debris was calcu-lated for each group and subjected to statistical analysis. Results. ANOVA was used to compare the mean dry weights of the debris extruded in the three groups, followedby post hoc Tukey tests for multiple comparisons the between groups. Highly significant differences were found in the amount of debris extruded among all the groups (P<0.001. The ProTaper group exhibited the highest mean debris weight (0.8293±0.05433 mg and the RaCe system exhibited the lowest mean debris weight (0.1280±0.01606 mg. Conclusion. All the systems tested resulted in apical extrusion of debris. However, the hand ProTaper files extruded a sig-nificantly higher amount of debris than GT and RaCe systems.

In Vitro Comparison of Apically Extruded Debris during Root Canal Preparation of Mandibular Premolars with Manual and Rotary Instruments

Science.gov (United States)

Soi, Sonal; Yadav, Suman; Sharma, Sumeet; Sharma, Mohit

2015-01-01

Background and aims. During root canal preparation, debris extruded beyond the apical foramen may result in periapical inflammation and postoperative pain. To date no root canal preparation method has been developed that extrudes no periapical debris. The purpose of this study was to identify a system leading to minimal extrusion of debris from the apical foramen. The study was conducted to comparatively evaluate the amount of apical extrusion of debris during root canal preparation using hand ProTaper and GT rotary and RaCe rotary instruments using crown-down technique. Materials and methods. Ninety freshly extracted human single-rooted mandibular premolars were equally assigned to three groups (n=30). The root canals were instrumented using hand ProTaper, GT rotary and RaCe rotary systems. Debris and irrigant extruded from the apical foramen were collected into vials. The mean weight of the remaining debris was calculated for each group and subjected to statistical analysis. Results. ANOVA was used to compare the mean dry weights of the debris extruded in the three groups, followedby post hoc Tukey tests for multiple comparisons the between groups. Highly significant differences were found in the amount of debris extruded among all the groups (P<0.001). The ProTaper group exhibited the highest mean debris weight (0.8293±0.05433 mg) and the RaCe system exhibited the lowest mean debris weight (0.1280±0.01606 mg). Conclusion. All the systems tested resulted in apical extrusion of debris. However, the hand ProTaper files extruded a significantly higher amount of debris than GT and RaCe systems. PMID:26697144

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

Science.gov (United States)

Monin, Leticia; Griffiths, Kristin L.; Lam, Wing Y.; Gopal, Radha; Kang, Dongwan D.; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K.; Mitreva, Makedonka; Rosa, Bruce A.; Ramos-Payan, Rosalio; Morrison, Thomas E.; Murray, Peter J.; Rangel-Moreno, Javier; Pearce, Edward J.; Khader, Shabaana A.

2015-01-01

Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1–expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1–expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB. PMID:26571397

Steam generator fretting-wear damage: A summary of recent findings

International Nuclear Information System (INIS)

Guerout, F.M.; Fisher, N.J.

1999-01-01

Flow-induced vibration of steam generator (SG) tubes may sometimes result in fretting-wear damage at the tube-to-support locations. Fretting-wear damage predictions are largely based on experimental data obtained at representative test conditions. Fretting-wear of SG materials has been studied at the Chalk River Laboratories for two decades. Tests are conducted in fretting-wear test machines that simulate SG environmental conditions and tube-to-support dynamic interactions. A new high-temperature force and displacement measuring system was developed to monitor tube-to-support interaction (i.e., work-rate) at operating conditions. This improvement in experimental fretting-wear technology was used to perform a comprehensive study of the effect of various environment and design parameters on SG tube wear damage. This paper summarizes the results of tests performed over the past 4 yr to study the effect of temperature, water chemistry, support geometry, and tube material on fretting-wear. The results show a significant effect of temperature on tube wear damage. Therefore, fretting-wear tests must be performed at operating temperatures in order to be relevant. No significant effect of the type of water treatment on tube wear damage was observed. For predominantly impacting motion, the wear of SG tubes in contact with 410 stainless steel is similar regardless of whether Alloy 690 or Alloy 800 is used as tubing material or whether lattice bars or broached hole supports are used. Based on results presented in this paper, an average wear coefficient value is recommended that is used for the prediction of SG tube wear depth versus time

Wear behaviour of coating of aluminium matrix composites fabricated by thermal spray method; Comportamiento a desgaste de recubrimientos de material compuesto de matriz de aluminio fabricados por proyeccion termica

Energy Technology Data Exchange (ETDEWEB)

Campo, M.; Escalera, M. D.; Torres, B.; Rams, J.; Urena, A.

2007-07-01

In this work, the wear behaviour of coatings made of aluminium matrix composites reinforced with 20% of SiC particles and manufactured by thermal spray method with oxyacetylene flame has been investigated. the wear behaviour between coating with uncoated particles and sol-gel silica coated ones heat treated at 500 degree centigree and 725 degree centigree have been compared. The sprayed coatings with silica coated particles are more homogeneous and less porous due to increase of wettability by molten aluminium that takes place on coated particles. The microstructure of the sprayed coatings, the wear surfaces and the wear debris have been analysed using optical microscopy, scanning electron microscopy and micro-analysis techniques (EDX). The results show a smaller wear rate, a lower friction coefficient and more reduced loss of mass for the coatings sprayed with particles with sol-gel silica coatings than those made with uncoated particles. (Author) 15 refs.

Effect of load and reciprocating velocity on the transition from mild to severe wear behavior of Al-Si-SiCp composites in reciprocating conditions

International Nuclear Information System (INIS)

Rajeev, V.R.; Dwivedi, D.K.; Jain, S.C.

2010-01-01

In the present paper, the effect of normal load and reciprocating velocity on transition from mild to severe wear of A319/15%SiC p , A336/15%SiC p , and A390/15%SiC p composites have been reported. Composites were produced through liquid metal metallurgy route. Adhesive wear behavior of composites was studied under dry reciprocating conditions using indigenously developed reciprocating friction wear test rig conforming to ASTM Standard G133-05. It was found that increase in normal load increases wear rate and depending upon the reciprocating velocity and type of composites, mode of wear changes from mild oxidative to severe metallic wear was noticed. The load corresponding to the transition from mild to severe wear usually termed as transition load was found to decrease with increase in reciprocating velocity and reduction in silicon content in the alloys used for the development of Al-Si-SiC p composites. At 1 m/s reciprocating velocity, the transition load for A319/15%SiC p , A336/15%SiC p and A390/15%SiC p composites were found to be in the range of 60-90 N, 60-105 N and 60-120 N respectively. Scanning electron microscope (SEM) study of wear surface and wear debris were conducted to analyze the mode of wear and operating wear mechanism. Severe wear was characterized by massive plastic deformation and gross material removal while the mild wear was found to be associated with delamination and scoring as main wear mechanisms responsible for material loss. Wear mechanism maps for different Al-(6-18)%Si-15%SiC p composites were proposed in reciprocating contacts.

Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

Energy Technology Data Exchange (ETDEWEB)

Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States); Shen, Jianliang; Patel-Vayas, Kinal; Gow, Andrew J. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States)

2012-05-15

Pulmonary toxicity induced by sulfur mustard and related vesicants is associated with oxidative stress. In the present studies we analyzed the role of reactive nitrogen species (RNS) generated via inducible nitric oxide synthase (iNOS) in lung injury and inflammation induced by vesicants using 2-chloroethyl ethyl sulfide (CEES) as a model. C57Bl/6 (WT) and iNOS −/− mice were sacrificed 3 days or 14 days following intratracheal administration of CEES (6 mg/kg) or control. CEES intoxication resulted in transient (3 days) increases in bronchoalveolar lavage (BAL) cell and protein content in WT, but not iNOS −/− mice. This correlated with expression of Ym1, a marker of oxidative stress in alveolar macrophages and epithelial cells. In contrast, in iNOS −/− mice, Ym1 was only observed 14 days post-exposure in enlarged alveolar macrophages, suggesting that they are alternatively activated. This is supported by findings that lung tumor necrosis factor and lipocalin Lcn2 expression, mediators involved in tissue repair were also upregulated at this time in iNOS −/− mice. Conversely, CEES-induced increases in the proinflammatory genes, monocyte chemotactic protein-1 and cyclooxygenase-2, were abrogated in iNOS −/− mice. In WT mice, CEES treatment also resulted in increases in total lung resistance and decreases in compliance in response to methacholine, effects blunted by loss of iNOS. These data demonstrate that RNS, generated via iNOS play a role in the pathogenic responses to CEES, augmenting oxidative stress and inflammation and suppressing tissue repair. Elucidating inflammatory mechanisms mediating vesicant-induced lung injury is key to the development of therapeutics to treat mustard poisoning. -- Highlights: ► Lung injury, inflammation and oxidative stress are induced by the model vesicant CEES ► RNS generated via iNOS are important in the CEES-induced pulmonary toxicity ► iNOS −/− mice are protected from CEES-induced lung toxicity and

Models of Inflammation: Carrageenan- or Complete Freund's Adjuvant (CFA)-Induced Edema and Hypersensitivity in the Rat.

Science.gov (United States)

McCarson, Kenneth E

2015-09-01

Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the processing of pain sensation at CNS sites, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. Detailed in this unit are methods to elicit and measure carrageenan- and complete Freund's adjuvant (CFA)-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections into either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) or by the trigeminal ganglion neurons (vibrissal pad). Copyright © 2015 John Wiley & Sons, Inc.

Nuclear Fuel Fretting Mechanisms in a Room Temperature Unlubricated Condition

Energy Technology Data Exchange (ETDEWEB)

Lee, Young Ho; Kim, Hyung Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2008-10-15

Recently, efforts for evaluating the fretting wear mechanism have been carried out by many researchers in various conditions. In an unlubricated condition, especially, effects of a wear debris and/or its layer on the fretting wear behavior were proposed that the formation of a well-developed glaze layer has a beneficial effect for decreasing a friction coefficient. Otherwise, a wear rate was accelerated by a third-body abrasion. At this time, it is well known that wear debris behaviors are affected by test variables such as a temperature, environment, material characteristics, etc. In a nuclear fuel fretting, however, its contact condition is quite different when compared with general fretting wear studies and could be summarized as the following; first, a fuel rod is supported by spacer grid springs and dimples that were elastically deformable. This results in a unique friction loop and a different fretting mechanism when a fuel rod is vibrated due to a flow-induced vibration (FIV). Next, it is possible that some region of the wear scar area with a specific spring shape condition could be hidden due to different wear debris behavior. So, some of the wear debris layers could be found on the worn surfaces in previous studies even though fretting wear tests were performed in a water lubricated condition. Finally, initial contact condition could be changed both an actual operating condition in power plants (i.e. high temperature and pressurized water (HTHP) under severe irradiation conditions) and the fretting wear tests for evaluating the wear resistant spring in lab conditions (i.e. from room temperature to HTHP without irradiation conditions) due to material degradations and the formation of the wear scar, respectively. In summary, the spring shape effect and the variation of the contact condition with increasing fretting cycle should be evaluated in order to improve the wear resistance of the spacer grid spring. So, in this study, fretting wear tests have been

Aerobic training suppresses exercise-induced lipid peroxidation and inflammation in overweight/obese adolescent girls.

Science.gov (United States)

Youssef, Hala; Groussard, Carole; Lemoine-Morel, Sophie; Pincemail, Joel; Jacob, Christophe; Moussa, Elie; Fazah, Abdallah; Cillard, Josiane; Pineau, Jean-Claude; Delamarche, Arlette

2015-02-01

This study aimed to determine whether aerobic training could reduce lipid peroxidation and inflammation at rest and after maximal exhaustive exercise in overweight/obese adolescent girls. Thirty-nine adolescent girls (14-19 years old) were classified as nonobese or overweight/obese and then randomly assigned to either the nontrained or trained group (12-week multivariate aerobic training program). Measurements at the beginning of the experiment and at 3 months consisted of body composition, aerobic fitness (VO2peak) and the following blood assays: pre- and postexercise lipid peroxidation (15F2a-isoprostanes [F2-Isop], lipid hydroperoxide [ROOH], oxidized LDL [ox-LDL]) and inflammation (myeloperoxidase [MPO]) markers. In the overweight/ obese group, the training program significantly increased their fat-free mass (FFM) and decreased their percentage of fat mass (%FM) and hip circumference but did not modify their VO2peak. Conversely, in the nontrained overweight/obese group, weight and %FM increased, and VO2peak decreased, during the same period. Training also prevented exercise-induced lipid peroxidation and/or inflammation in overweight/obese girls (F2-Isop, ROOH, ox-LDL, MPO). In addition, in the trained overweight/obese group, exercise-induced changes in ROOH, ox-LDL and F2-Isop were correlated with improvements in anthropometric parameters (waist-to-hip ratio, %FM and FFM). In conclusion aerobic training increased tolerance to exercise-induced oxidative stress in overweight/obese adolescent girls partly as a result of improved body composition.

Dental wear, wear rate, and dental disease in the African apes.

Science.gov (United States)

Elgart, Alison A

2010-06-01

The African apes possess thinner enamel than do other hominoids, and a certain amount of dentin exposure may be advantageous in the processing of tough diets eaten by Gorilla. Dental wear (attrition plus abrasion) that erodes the enamel exposes the underlying dentin and creates additional cutting edges at the dentin-enamel junction. Hypothetically, efficiency of food processing increases with junction formation until an optimal amount is reached, but excessive wear hinders efficient food processing and may lead to sickness, reduced fecundity, and death. Occlusal surfaces of molars and incisors in three populations each of Gorilla and Pan were videotaped and digitized. The quantity of incisal and molar occlusal dental wear and the lengths of dentin-enamel junctions were measured in 220 adult and 31 juvenile gorilla and chimpanzee skulls. Rates of dental wear were calculated in juveniles by scoring the degree of wear between adjacent molars M1 and M2. Differences were compared by principal (major) axis analysis. ANOVAs compared means of wear amounts. Pearson correlation coefficients were calculated to compare the relationship between molar wear and incidence of dental disease. Results indicate that quantities of wear are significantly greater in permanent incisors and molars and juvenile molars of gorillas compared to chimpanzees. The lengths of dentin-enamel junctions were predominantly suboptimal. Western lowland gorillas have the highest quantities of wear and the most molars with suboptimal wear. The highest rates of wear are seen in Pan paniscus and Pan t. troglodytes, and the lowest rates are found in P.t. schweinfurthii and G. g. graueri. Among gorillas, G. b. beringei have the highest rates but low amounts of wear. Coefficients between wear and dental disease were low, but significant when all teeth were combined. Gorilla teeth are durable, and wear does not lead to mechanical senescence in this sample.

Microstructure and wear behavior of stellite 6 cladding on 17-4 PH stainless steel

Energy Technology Data Exchange (ETDEWEB)

Gholipour, A. [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Shamanian, M., E-mail: shamanian@cc.iut.ac.ir [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Ashrafizadeh, F. [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of)

2011-04-07

Research highlights: > The microstructure of the surface layer consisted of carbides embedded in a Co-rich solid solution with dendritic structure. Primary phases formed during the process were identified as Co(FCC) and lamellar eutectic phases (M{sub 23}C{sub 6}, M{sub 6}C, Cr{sub 7}C{sub 3}). > Microhardness profiles showed that hardness increases from interface to the coating surface. This is due to the finer size of the grains at coating surface in comparison to that at interface and also diffusion of Fe adjacent to the interface. > The delamination was suggested as the dominant mechanism of the wear. In this regard, plate-like wear debris consisted of voids and cracks. In addition, due to increase in surface temperature, Cr{sub 2}O{sub 3} oxide phase was formed during wear tests. - Abstract: This paper deals with the investigation of the microstructure and wear behavior of the stellite 6 cladding on precipitation hardening martensitic stainless steel (17-4PH) using gas tungsten arc welding (GTAW) method. 17-4 PH stainless steel is widely used in oil and gas industries. Optical metallography, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were employed to study the microstructure and wear mechanisms. X-ray diffraction analysis was also used to identify phases formed in the coating. The results showed that the microstructure of the surface layer consisted of carbides embedded in a Co-rich solid solution with a dendritic structure. In addition, the dendritic growth in the coating was epitaxial. Primary phases formed during the process were Co (fcc), Co (hcp), lamellar eutectic phases, M{sub 23}C{sub 6} and Cr{sub 7}C{sub 3} type carbides. The results of the wear tests indicated that the delamination was the dominant mechanism. So, it is necessary to apply an inter-layer between the substrate and top coat.

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

DEFF Research Database (Denmark)

Andersen, Hjalte Holm; Imai, Yosuke; Petersen, Kristian Kjær

2016-01-01

This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar...... forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive...... signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers....

Sleep apnea is associated with bronchial inflammation and continuous positive airway pressure-induced airway hyperresponsiveness.

Science.gov (United States)

Devouassoux, Gilles; Lévy, Patrick; Rossini, Eliane; Pin, Isabelle; Fior-Gozlan, Michèle; Henry, Mireille; Seigneurin, Daniel; Pépin, Jean-Louis

2007-03-01

Obstructive sleep apnea syndrome (OSA) is associated with systemic and upper airway inflammation. Pharyngeal inflammation has a potential role in upper airway collapse, whereas systemic inflammation relates to cardiovascular morbidity. However, the presence of an inflammatory involvement of lower airway has been poorly investigated. The aim of the study was to demonstrate an inflammatory process at the bronchial level in patients with OSA and to analyze effects of continuous positive airway pressure (CPAP) application and humidification on bronchial mucosa. The study was conducted by using sequential induced sputum for cell analysis and IL-8 production, nitric oxide exhalation measurement, and methacholine challenge before and after CPAP. Bronchial neutrophilia and a high IL-8 concentration were observed in untreated OSA compared with controls (75% +/- 20% vs 43% +/- 12%, P Obstructive sleep apnea syndrome is associated with bronchial inflammation. Our data demonstrate CPAP effect on the development of AHR, possibly facilitated by the pre-existing inflammation. Both issues should be evaluated during long-term CPAP use. Results showing a spontaneous bronchial inflammation in OSA and the development of a CPAP-related AHR require a long-term follow-up to evaluate consequences on chronic bronchial obstruction.

Impact Fretting Wear Behavior of Alloy 690 Tubes in Dry and Deionized Water Conditions

Institute of Scientific and Technical Information of China (English)

Zhen-Bing Cai; Jin-Fang Peng; Hao Qian; Li-Chen Tang; Min-Hao Zhu

2017-01-01

The impact fretting wear has largely occurred at nuclear power device induced by the flow-induced vibration,and it will take potential hazards to the service of the equipment.However,the present study focuses on the tangential fretting wear of alloy 690 tubes.Research on impact fretting wear of alloy 690 tubes is limited and the related research is imminent.Therefore,impact fretting wear behavior of alloy 690 tubes against 304 stainless steels is investigated.Deionized water is used to simulate the flow environment of the equipment,and the dry environment is used for comparison.Varied analytical techniques are employed to characterize the wear and tribochemical behavior during impact fretting wear.Characterization results indicate that cracks occur at high impact load in both water and dry equipment;however,the water as a medium can significantly delay the cracking time.The crack propagation behavior shows a jagged shape in the water,but crack extended disorderly in dry equipment because the water changed the stress distribution and retarded the friction heat during the wear process.The SEM and XPS analysis shows that the main failure mechanisms of the tube under impact fretting are fatigue wear and friction oxidation.The effect of medium(water) on fretting wear is revealed,which plays a potential and promising role in the service of nuclear power device and other flow equipments.

Microstructure and wear characterization of aluminum matrix composites reinforced with industrial waste fly ash particulates synthesized by friction stir processing

Energy Technology Data Exchange (ETDEWEB)

Dinaharan, I., E-mail: dinaweld2009@gmail.com [Department of Mechanical Engineering Science, University of Johannesburg, Auckland Park Kingsway Campus, Johannesburg 2006 (South Africa); Nelson, R., E-mail: nelson.90.mech@gmail.com [Department of Mechanical Engineering, Karunya University, Coimbatore 641114, Tamil Nadu (India); Vijay, S.J., E-mail: vijayjoseph.2001@gmail.com [Center for Research in Metallurgy, School of Mechanical Sciences, Karunya University, Coimbatore 641114, Tamil Nadu (India); Akinlabi, E.T., E-mail: etakinlabi@uj.ac.za [Department of Mechanical Engineering Science, University of Johannesburg, Auckland Park Kingsway Campus, Johannesburg 2006 (South Africa)

2016-08-15

Fly ash (FA) is a waste product of coal combustion in thermal power plants which is available in massive quantities all over the world causing land pollution. This paper reports the characterization of AA6061 aluminum matrix composites (AMCs) reinforced with FA particles synthesized using friction stir processing (FSP). The volume fraction of FA particles was varied from 0 to 18 in steps of 6. The prepared AMCs were characterized using optical microscopy (OM), scanning electron microscopy (SEM) and electron backscattered diagram (EBSD). The wear rate was estimated using a pin-on-disc wear apparatus. FA particles were observed to be distributed homogeneously in the AMC irrespective of the location within the stir zone. The EBSD micrographs revealed remarkable grain refinement in the AMC. The incorporation of FA particles enhanced the microhardness and wear resistance of the AMC. The strengthening mechanisms of the AMC were discussed and correlated to the observed microstructures. The wear mechanisms were identified by characterizing the wear debris and worn surfaces. - Highlights: •Industrial waste fly ash was used to produce aluminum matrix composites. •Friction stir processing was used to produce AA6061/Fly Ash composite. •Fly ash particles refined the grains of aluminum matrix. •Fly ash particles enhanced the hardness and wear resistance. •Successful utilization of fly ash to make aluminum composites reduces land pollution.

Prunella vulgaris Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation

Directory of Open Access Journals (Sweden)

Ho Sub Lee

2012-01-01

Full Text Available Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV on high glucose (HG-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1, and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS. HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1, eNOS, and nuclear factor E2-related factor 2 (Nrf2, which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that Prunella vulgaris may be a possible therapeutic approach to the inhibition of diabetic vascular diseases.

High-density lipoproteins inhibit urate crystal-induced inflammation in mice

OpenAIRE

Scanu Anna; Luisetto Roberto; Oliviero Francesca; Gruaz Lyssia; Sfriso Paolo; Burger Danielle; Punzi Leonardo

2015-01-01

Objectives To investigate the effects and mechanisms of action of high density lipoproteins (HDL) in monosodium urate (MSU) crystal induced inflammation—that is gouty inflammation in vivo. Methods Air pouches raised on the backs of mice were injected with MSU crystals or tumour necrosis factor (TNF) in the presence or absence of HDL and/or interleukin (IL) 1 receptor antagonist (IL 1Ra) for 3 h. Leucocyte count and neutrophil percentage in pouch fluids were measured using a haemocytometer an...

Comparison of Apical Extrusion of Debris by Using Single-File, Full-Sequence Rotary and Reciprocating Systems.

Science.gov (United States)

Ehsani, Maryam; Farhang, Robab; Harandi, Azadeh; Tavanafar, Saeid; Raoof, Maryam; Galledar, Saeedeh

2016-11-01

During root canal preparation, apical extrusion of debris can cause inflammation, flare-ups, and delayed healing. Therefore, instrumentation techniques that cause the least extrusion of debris are desirable. This study aimed to compare apical extrusion of debris by five single-file, full-sequence rotary and reciprocating systems. One hundred twenty human mandibular premolars with similar root lengths, apical diameters, and canal curvatures were selected and randomly assigned to six groups (n=20): Reciproc R25 (25, 0.08), WaveOne Primary (25, 0.08), OneShape (25, 0.06), F360 (25, 0.04), Neoniti A1 (25, 0.08), and ProTaper Universal. Instrumentation of the root canals was performed in accordance with the manufacturers' instructions. Each tooth's debris was collected in a pre-weighed vial. After drying the debris in an incubator, the mass was measured three times consecutively; the mean was then calculated. The preparation time by each system was also measured. For data analysis, one-way ANOVA and Games-Howell post hoc test were used. The mean masses (±standard deviation) of the apical debris were as follows: 2.071±1.38mg (ProTaper Universal), 1.702±1.306mg (Neoniti A1), 1.295±0.839mg (OneShape), 1.109±0.676mg (WaveOne), 0.976±0.478mg (Reciproc) and 0.797±0.531mg (F360). Compared to ProTaper Universal, F360 generated significantly less debris (P=0.02). The ProTaper system required the longest preparation time (mean=88.6 seconds); the Reciproc (P=0.008), OneShape (P=0.006), and F360 (P=0.001) required significantly less time (P<0.05). All instruments caused extrusion of debris through the apex. The F360 produced significantly less debris than did the ProTaper Universal.

PPARs, Obesity, and Inflammation

Directory of Open Access Journals (Sweden)

Rinke Stienstra

2007-01-01

Full Text Available The worldwide prevalence of obesity and related metabolic disorders is rising rapidly, increasing the burden on our healthcare system. Obesity is often accompanied by excess fat storage in tissues other than adipose tissue, including liver and skeletal muscle, which may lead to local insulin resistance and may stimulate inflammation, as in steatohepatitis. In addition, obesity changes the morphology and composition of adipose tissue, leading to changes in protein production and secretion. Some of these secreted proteins, including several proinflammatory mediators, may be produced by macrophages resident in the adipose tissue. The changes in inflammatory status of adipose tissue and liver with obesity feed a growing recognition that obesity represents a state of chronic low-level inflammation. Various molecular mechanisms have been implicated in obesity-induced inflammation, some of which are modulated by the peroxisome proliferator-activated receptors (PPARs. PPARs are ligand-activated transcription factors involved in the regulation of numerous biological processes, including lipid and glucose metabolism, and overall energy homeostasis. Importantly, PPARs also modulate the inflammatory response, which makes them an interesting therapeutic target to mitigate obesity-induced inflammation and its consequences. This review will address the role of PPARs in obesity-induced inflammation specifically in adipose tissue, liver, and the vascular wall.

Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by μ-opioid receptor internalization

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Chen, Wenling; Marvizón, Juan Carlos G.

2009-01-01

The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using μ-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hindpaw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hindpaw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected Complete Freund's Adjuvant (CFA) in the hindpaw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hindpaw. These results show that acute inflammation, but not chronic inflammation, induce segmental opioid release in the spinal cord that involves supraspinal signals. PMID:19298846

Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization.

Science.gov (United States)

Chen, W; Marvizón, J C G

2009-06-16

The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using mu-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hind paw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hind paw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected complete Freund's adjuvant (CFA) in the hind paw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hind paw. These results show that acute inflammation, but not chronic inflammation, induces segmental opioid release in the spinal cord that involves supraspinal signals.

Wear behavior of A356/M{sub 7}C{sub 3} and A356/SiC particulate metal matrix composites

Energy Technology Data Exchange (ETDEWEB)

Turhan, H. [Univ. of Firat, Dept. of Metallurgy, Elazig (Turkey); Yilmaz, O. [Univ. of Firat, Dept. of Metallurgical Engineering, Elazig (Turkey)

2002-06-01

The stability of M{sub 7}C{sub 3} carbides as reinforcement for A356 materials for tribological applications has been investigated. For this purpose, A356/M{sub 7}C{sub 3}, A356/SiC and A356/M{sub 7}C{sub 3}/SiC composites were prepared by powder metallurgy and tested at room temperature against SAE 4620 steel ring and AISI 304 stainless steel counterfaces under loads of 10 - 150 N. For comparison, also unreinforced A356 specimens were processed and tested under the same conditions. The tribological behavior was evaluated by microstructural examination of the wear-effected zones and by weight loss measurements of the specimens and counterfaces. The wear behavior of A356/M{sub 7}C{sub 3} composite gave an excellent result as function of the applied load because the M{sub 7}C{sub 3} particles act as load-bearing elements due to their excellent bonding to the Al matrix, and their interfaces withtood the wear stresses even at the highest applied load. Moreover, the M{sub 7}C{sub 3} particles limited the incorporation of wear debris into the Al matrix and reduced the wear damage occasioned to the steel counterfaces compared to that of A356 Al alloy. (orig.)

Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity

International Nuclear Information System (INIS)

Liu, Wei-Xin; Wang, Ting; Zhou, Feng; Wang, Ying; Xing, Jun-Wei; Zhang, Shen; Gu, Shou-Zhi; Sang, Li-Xuan; Dai, Cong; Wang, Hai-Lan

2015-01-01

Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentary group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity. - Highlights: • Obesity down-regulates PPAR-γ in the colon. • Down-regulated colonic PPAR-γ may facilitate inflammatory

Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity

Energy Technology Data Exchange (ETDEWEB)

Liu, Wei-Xin, E-mail: weixinliu@yahoo.com [Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Wang, Ting; Zhou, Feng; Wang, Ying; Xing, Jun-Wei; Zhang, Shen [Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Gu, Shou-Zhi [Department of Anatomy, Seirei Christopher College, Hamamatsu 433-8558 (Japan); Sang, Li-Xuan [Department of Cadre Ward II, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Dai, Cong [Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Wang, Hai-Lan [Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, Guangdong (China)

2015-04-10

Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentary group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity. - Highlights: • Obesity down-regulates PPAR-γ in the colon. • Down-regulated colonic PPAR-γ may facilitate inflammatory

DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway

Science.gov (United States)

Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the...

CoCrMo alloy vs. UHMWPE Particulate Implant Debris Induces Sex Dependent Aseptic Osteolysis Responses In Vivo using a Murine Model

Science.gov (United States)

Landgraeber, Stefan; Samelko, Lauryn; McAllister, Kyron; Putz, Sebastian; Jacobs, Joshua.J.; Hallab, Nadim James

2018-01-01

Background: The rate of revision for some designs of total hip replacements due to idiopathic aseptic loosening has been reported as higher for women. However, whether this is environmental or inherently sex-related is not clear. Objective: Can particle induced osteolysis be sex dependent? And if so, is this dependent on the type of implant debris (e.g. metal vs polymer)? The objective of this study was to test for material dependent inflammatory osteolysis that may be linked to sex using CoCrMo and implant grade conventional polyethylene (UHMWPE), using an in vivo murine calvaria model. Methods: Healthy 12 week old female and male C57BL/6J mice were treated with UHMWPE (1.0um ECD) or CoCrMo particles (0.9um ECD) or received sham surgery. Bone resorption was assessed by micro-computed tomography, histology and histomorphometry on day 12 post challenge. Results: Female mice that received CoCrMo particles showed significantly more inflammatory osteolysis and bone destruction compared to the females who received UHMWPE implant debris. Moreover, females challenged with CoCrMo particles exhibited 120% more inflammatory bone loss compared to males (p<0.01) challenged with CoCrMo implant debris (but this was not the case for UHMWPE particles). Conclusion: We demonstrated sex-specific differences in the amount of osteolysis resulting from CoCrMo particle challenge. This suggests osteo-immune responses to metal debris are preferentially higher in female compared to male mice, and supports the contention that there may be inherent sex related susceptibility to some types of implant debris. PMID:29785221

Loss of hypoxia-inducible factor 2 alpha in the lung alveolar epithelium of mice leads to enhanced eosinophilic inflammation in cobalt-induced lung injury.

Science.gov (United States)

Proper, Steven P; Saini, Yogesh; Greenwood, Krista K; Bramble, Lori A; Downing, Nathaniel J; Harkema, Jack R; Lapres, John J

2014-02-01

Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2α(Δ/Δ)) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2α(Δ/Δ) mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2α(Δ/Δ) and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung.

Involvement of purinergic system in inflammation and toxicity induced by copper in zebrafish larvae

Energy Technology Data Exchange (ETDEWEB)

Leite, Carlos Eduardo, E-mail: carlos.leite@pucrs.br [Instituto de Toxicologia e Farmacologia, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, CEP 90619-900 (Brazil); Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, CEP 90035-003 (Brazil); Maboni, Lucas de Oliveira [Instituto de Toxicologia e Farmacologia, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, CEP 90619-900 (Brazil); Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, CEP 90619-900 (Brazil); Cruz, Fernanda Fernandes [Instituto de Toxicologia e Farmacologia, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, CEP 90619-900 (Brazil); Faculdade de Farmácia, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, CEP 90619-900 (Brazil); Rosemberg, Denis Broock [Programa de Pós-graduação em Ciências Ambientais, Universidade Comunitária da Região de Chapecó, Chapecó, CEP 89809-000 (Brazil); and others

2013-11-01

The use of zebrafish (Danio rerio) is increasing as an intermediate preclinical model, to prioritize drug candidates for mammalian testing. As the immune system of the zebrafish is quite similar to that of mammals, models of inflammation are being developed for the screening of new drugs. The characterization of these models is crucial for studies that seek for mechanisms of action and specific pharmacological targets. It is well known that copper is a metal that induces damage and cell migration to hair cells of lateral line of zebrafish. Extracellular nucleotides/nucleosides, as ATP and adenosine (ADO), act as endogenous signaling molecules during tissue damage by exerting effects on inflammatory and immune responses. The present study aimed to characterize the inflammatory status, and to investigate the involvement of the purinergic system in copper-induced inflammation in zebrafish larvae. Fishes of 7 days post-fertilization were exposed to 10 μM of copper for a period of 24 h. The grade of oxidative stress, inflammatory status, copper uptake, the activity and the gene expression of the enzymes responsible for controlling the levels of nucleotides and adenosine were evaluated. Due to the copper accumulation in zebrafish larvae tissues, the damage and oxidative stress were exacerbated over time, resulting in an inflammatory process involving IL-1β, TNF-α, COX-2 and PGE{sub 2}. Within the purinergic system, the mechanisms that control the ADO levels were the most involved, mainly the reactions performed by the isoenzyme ADA 2. In conclusion, our data shed new lights on the mechanisms related to copper-induced inflammation in zebrafish larvae. - Graphical abstract: This scheme provides a chronological proposition for the biochemical events induced by copper in zebrafish larvae. The dashed line shows the absorption of copper over the exposure time. After 1 h of exposure to copper, the release of PGE{sub 2} occurs, followed by an increase of MPO (as a consequence

Involvement of purinergic system in inflammation and toxicity induced by copper in zebrafish larvae

International Nuclear Information System (INIS)

Leite, Carlos Eduardo; Maboni, Lucas de Oliveira; Cruz, Fernanda Fernandes; Rosemberg, Denis Broock

2013-01-01

The use of zebrafish (Danio rerio) is increasing as an intermediate preclinical model, to prioritize drug candidates for mammalian testing. As the immune system of the zebrafish is quite similar to that of mammals, models of inflammation are being developed for the screening of new drugs. The characterization of these models is crucial for studies that seek for mechanisms of action and specific pharmacological targets. It is well known that copper is a metal that induces damage and cell migration to hair cells of lateral line of zebrafish. Extracellular nucleotides/nucleosides, as ATP and adenosine (ADO), act as endogenous signaling molecules during tissue damage by exerting effects on inflammatory and immune responses. The present study aimed to characterize the inflammatory status, and to investigate the involvement of the purinergic system in copper-induced inflammation in zebrafish larvae. Fishes of 7 days post-fertilization were exposed to 10 μM of copper for a period of 24 h. The grade of oxidative stress, inflammatory status, copper uptake, the activity and the gene expression of the enzymes responsible for controlling the levels of nucleotides and adenosine were evaluated. Due to the copper accumulation in zebrafish larvae tissues, the damage and oxidative stress were exacerbated over time, resulting in an inflammatory process involving IL-1β, TNF-α, COX-2 and PGE 2 . Within the purinergic system, the mechanisms that control the ADO levels were the most involved, mainly the reactions performed by the isoenzyme ADA 2. In conclusion, our data shed new lights on the mechanisms related to copper-induced inflammation in zebrafish larvae. - Graphical abstract: This scheme provides a chronological proposition for the biochemical events induced by copper in zebrafish larvae. The dashed line shows the absorption of copper over the exposure time. After 1 h of exposure to copper, the release of PGE 2 occurs, followed by an increase of MPO (as a consequence of

Inhibition of ROS and inflammation by an imidazopyridine derivative X22 attenuate high fat diet-induced arterial injuries.

Science.gov (United States)

Li, Weixin; Wang, Lintao; Huang, Weijian; Skibba, Melissa; Fang, Qilu; Xie, Longteng; Wei, Tiemin; Feng, Zhiguo; Liang, Guang

2015-09-01

Obesity is strongly associated with the cause of structural and functional changes of the artery. Oxidative stress and inflammation play a critical role in the development of obesity-induced cardiovascular disorders. Our group previously found that an imidazopyridine derivative X22 showed excellent anti-inflammatory activity in LPS-stimulated macrophages. This study was designed to investigate the protective effects of X22 on high fat diet (HFD)-induced arterial injury and its underlying mechanisms. We observed that palmitate (PA) treatment in HUVECs induced a marked increase in reactive oxygen species, inflammation, apoptosis, and fibrosis. All of these changes were effectively suppressed by X22 treatment in a dose-dependent manner, associated with NF-κB inactivation and Nrf-2 activation. In HFD-fed rats, administration of X22 at 10mg/kg significantly decreased the arterial inflammation and oxidative stress, and eventually improved the arterial matrix remodeling and apoptosis. X22 at 10mg/kg showed a comparable bioactivity with the positive control, curcumin at 50mg/kg. The in vivo beneficial effects of X22 are also associated with its ability to increase Nrf2 expression and inhibit NF-κB activation in the artery of HFD-fed rats. Overall, these results suggest that X22 may have therapeutic potential in the treatment of obesity-induced artery injury via regulation of Nrf2-mediated oxidative stress and NF-κB-mediated inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Protective Roles for RGS2 in a Mouse Model of House Dust Mite-Induced Airway Inflammation.

Directory of Open Access Journals (Sweden)

Tresa George

Full Text Available The GTPase-accelerating protein, regulator of G-protein signalling 2 (RGS2 reduces signalling from G-protein-coupled receptors (GPCRs that signal via Gαq. In humans, RGS2 expression is up-regulated by inhaled corticosteroids (ICSs and long-acting β2-adrenoceptor agonists (LABAs such that synergy is produced in combination. This may contribute to the superior clinical efficacy of ICS/LABA therapy in asthma relative to ICS alone. In a murine model of house dust mite (HDM-induced airways inflammation, three weeks of intranasal HDM (25 μg, 3×/week reduced lung function and induced granulocytic airways inflammation. Compared to wild type animals, Rgs2-/- mice showed airways hyperresponsiveness (increased airways resistance and reduced compliance. While HDM increased pulmonary inflammation observed on hematoxylin and eosin-stained sections, there was no difference between wild type and Rgs2-/- animals. HDM-induced mucus hypersecretion was also unaffected by RGS2 deficiency. However, inflammatory cell counts in the bronchoalveolar lavage fluid of Rgs2-/- animals were significantly increased (57% compared to wild type animals and this correlated with increased granulocyte (neutrophil and eosinophil numbers. Likewise, cytokine and chemokine (IL4, IL17, IL5, LIF, IL6, CSF3, CXCLl, CXCL10 and CXCL11 release was increased by HDM exposure. Compared to wild type, Rgs2-/- animals showed a trend towards increased expression for many cytokines/chemokines, with CCL3, CCL11, CXCL9 and CXCL10 being significantly enhanced. As RGS2 expression was unaffected by HDM exposure, these data indicate that RGS2 exerts tonic bronchoprotection in HDM-induced airways inflammation. Modest anti-inflammatory and anti-remodelling roles for RGS2 are also suggested. If translatable to humans, therapies that maximize RGS2 expression may prove advantageous.

Involvement of prostaglandins and histamine in nickel wire-induced acute inflammation in mice.

Science.gov (United States)

Hirasawa, Noriyasu; Goi, Yoshiaki; Tanaka, Rina; Ishihara, Kenji; Ohtsu, Hiroshi; Ohuchi, Kazuo

2010-06-15

The irritancy of Nickel (Ni) ions has been well documented clinically. However, the chemical mediators involved in the acute inflammation induced by solid Ni are not fully understood. We used the Ni wire-implantation model in mice and examined roles of prostaglandins and histamine in plasma leakage in the acute phase. The subcutaneous implantation of a Ni wire into the back of mice induced plasma leakage from 8 to 24 h and tissue necrosis around the wire at 3 days, whereas the implantation of an aluminum wire induced no such inflammatory responses. An increase in the mRNA for cyclooxygenase (COX)-2 and HDC in cells around the Ni wire was detected 4 h after the implantation. The leakage of plasma at 8 h was inhibited by indomethacin in a dose-dependent manner. Dexamethasone and the p38 MAP kinase inhibitor SB203580 also inhibited the exudation of plasma consistent with the inhibition of the expression of COX-2 mRNA. Furthermore, plasma leakage was partially but siginificantly reduced in histamine H1 receptor knockout mice and histidine decarboxylase (HDC) knockout mice but not in H2 receptor knockout mice. These results suggested that the Ni ions released from the wire induced the expression of COX-2 and HDC, resulting in an increase in vascular permeability during the acute phase of inflammation. (c) 2009 Wiley Periodicals, Inc.

Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Lee, Ko Eun [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Eun Young [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Kyung Keun [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Lee, Jong Un [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Soo Wan, E-mail: skimw@chonnam.ac.kr [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)

2013-05-10

Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-κB pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs

Predicting railway wheel wear under uncertainty of wear coefficient, using universal kriging

International Nuclear Information System (INIS)

Cremona, Marzia A.; Liu, Binbin; Hu, Yang; Bruni, Stefano; Lewis, Roger

2016-01-01

Railway wheel wear prediction is essential for reliability and optimal maintenance strategies of railway systems. Indeed, an accurate wear prediction can have both economic and safety implications. In this paper we propose a novel methodology, based on Archard's equation and a local contact model, to forecast the volume of material worn and the corresponding wheel remaining useful life (RUL). A universal kriging estimate of the wear coefficient is embedded in our method. Exploiting the dependence of wear coefficient measurements with similar contact pressure and sliding speed, we construct a continuous wear coefficient map that proves to be more informative than the ones currently available in the literature. Moreover, this approach leads to an uncertainty analysis on the wear coefficient. As a consequence, we are able to construct wear prediction intervals that provide reasonable guidelines in practice. - Highlights: • Wear prediction is of outmost importance for reliability of railway systems. • Wear coefficient is essential in prediction through Archard's equation. • A novel methodology is developed to predict wear and RUL. • Universal kriging is used for wear coefficient and uncertainty estimation. • A simulation study and a real case application are provided.

Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats.

Science.gov (United States)

Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A; Hernández-Reyes, Ana Gabriela; Martínez-Galero, Elizdath

2015-08-01

One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity.

Inducible nitric oxide expression correlates with the level of inflammation in periapical cysts.

Science.gov (United States)

Matsumoto, Mariza Akemi; Ribeiro, Daniel Araki

2007-10-01

In an attempt to elucidate if inducible nitric oxide expression (iNOS) is correlated with the level of inflammation in periapical cysts with accuracy, the goal of this study was to evaluate the expression of iNOS in these ones. 30 cases were included in this study being iNOS evaluated by means of immunohistochemistry. Statistical analysis was performed by Kruskal-Wallis non-parametric test followed by the post-hoc Dunn's test. iNOS stain was detected throughout the epithelium, subepithelial fibroblasts and macrophages in all cases, indistinctly. Nevertheless, iNOS immunostaining in periapical cysts was different according to the levels of inflammation, being the strongest effect associated with intense inflammatory infiltrate. Taken together, our results indicate that immunoreactivity of iNOS was expressed in several cellular types present in periapical cyst, being positively correlated with the level of inflammation. Therefore, iNOS expression plays an important role in the pathogenesis of periapical cysts.

EDDA 1.0: integrated simulation of debris flow erosion, deposition and property changes

Science.gov (United States)

Chen, H. X.; Zhang, L. M.

2015-03-01

Debris flow material properties change during the initiation, transportation and deposition processes, which influences the runout characteristics of the debris flow. A quasi-three-dimensional depth-integrated numerical model, EDDA (Erosion-Deposition Debris flow Analysis), is presented in this paper to simulate debris flow erosion, deposition and induced material property changes. The model considers changes in debris flow density, yield stress and dynamic viscosity during the flow process. The yield stress of the debris flow mixture determined at limit equilibrium using the Mohr-Coulomb equation is applicable to clear water flow, hyper-concentrated flow and fully developed debris flow. To assure numerical stability and computational efficiency at the same time, an adaptive time stepping algorithm is developed to solve the governing differential equations. Four numerical tests are conducted to validate the model. The first two tests involve a one-dimensional debris flow with constant properties and a two-dimensional dam-break water flow. The last two tests involve erosion and deposition, and the movement of multi-directional debris flows. The changes in debris flow mass and properties due to either erosion or deposition are shown to affect the runout characteristics significantly. The model is also applied to simulate a large-scale debris flow in Xiaojiagou Ravine to test the performance of the model in catchment-scale simulations. The results suggest that the model estimates well the volume, inundated area, and runout distance of the debris flow. The model is intended for use as a module in a real-time debris flow warning system.

The effect of denture stability, occlusion, oral hygiene and smoking on denture-induced stomatitis

International Nuclear Information System (INIS)

Nimri, Gadeer Mukatash

2008-01-01

This longitudinal clinical investigation was undertaken to find out the effect of denture wearing habit (day versus day and night), denture hygiene and cigarette smoking habit on the frequency of denture induced stomatitis. Comparisons were made between 240 complete denture wearers, half of whom were asked to wear their dentures at the daytime only and the other half to wear the denture day and night. All these participants were male patients with a mean age of 57.6 years who had received maxillary complete acrylic dentures for the first time. Fifty percent of the samples were smokers. A standard method for examination of the mouth and denture construction, insertion and follow up were employed. Putative risk factors (denture wearing habits, denture hygiene and smoking) were investigated. Subjects were recalled 12 months after insertion to examine the quality of the denture and the condition of the maxillary mucosa. No significant correlation was found between deterioration of stability or occlusion and type of habitual use of the dentures (P > 0.05). Fourteen percent of the cases reported with inflamed maxillary mucosa. Deterioration of retention or occlusion separately showed no correlation with the condition of the mucosa. However, associated deterioration of both stability and occlusion proved to be significantly correlated with the occurrence of denture stomatitis (P < 0.05). Denture stomatitis was significantly more frequently with subjects wearing their dentures overnight compared with those who removed them (P < 0.05). A significant correlation was also found between cigarette smoking, poor oral hygiene and the presence of denture induced stomatitis (P < 0.05). Nocturnal denture wearing habit, deficient oral and denture hygiene, and cigarette smoking are all important predisposing factors to denture-induced stomatitis, however, none of these factors was the sole cause of mucosal inflammation. (author)

Assessment of wear dependence parameters in complex model of cutting tool wear

Science.gov (United States)

Antsev, A. V.; Pasko, N. I.; Antseva, N. V.

2018-03-01

This paper addresses wear dependence of the generic efficient life period of cutting tools taken as an aggregate of the law of tool wear rate distribution and dependence of parameters of this law's on the cutting mode, factoring in the random factor as exemplified by the complex model of wear. The complex model of wear takes into account the variance of cutting properties within one batch of tools, variance in machinability within one batch of workpieces, and the stochastic nature of the wear process itself. A technique of assessment of wear dependence parameters in a complex model of cutting tool wear is provided. The technique is supported by a numerical example.

Glyceroneogenesis is inhibited through HIV protease inhibitor-induced inflammation in human subcutaneous but not visceral adipose tissue

Science.gov (United States)

Leroyer, Stéphanie; Vatier, Camille; Kadiri, Sarah; Quette, Joëlle; Chapron, Charles; Capeau, Jacqueline; Antoine, Bénédicte

2011-01-01

Glyceroneogenesis, a metabolic pathway that participates during lipolysis in the recycling of free fatty acids to triglycerides into adipocytes, contributes to the lipid-buffering function of adipose tissue. We investigated whether glyceroneogenesis could be affected by human immunodeficiency virus (HIV) protease inhibitors (PIs) responsible or not for dyslipidemia in HIV-infected patients. We treated explants obtained from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depots from lean individuals. We observed that the dyslipidemic PIs nelfinavir, lopinavir and ritonavir, but not the lipid-neutral PI atazanavir, increased lipolysis and decreased glyceroneogenesis, leading to an increased release of fatty acids from SAT but not from VAT. At the same time, dyslipidemic PIs decreased the amount of perilipin and increased interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) secretion in SAT but not in VAT. Parthenolide, an inhibitor of the NFκB pathway, counteracted PI-induced increased inflammation and decreased glyceroneogenesis. IL-6 (100 ng) inhibited the activity of phosphoenolpyruvate carboxykinase, the key enzyme of glyceroneogenesis, in SAT but not in VAT. Our data show that dyslipidemic but not lipid-neutral PIs decreased glyceroneogenesis as a consequence of PI-induced increased inflammation in SAT that could have an affect on adipocytes and/or macrophages. These results add a new link between fat inflammation and increased fatty acids release and suggest a greater sensitivity of SAT than VAT to PI-induced inflammation. PMID:21068005

Evidence for a pathogenic role of nitric oxide in inflammation-induced osteoporosis.

Science.gov (United States)

Armour, K E; Van'T Hof, R J; Grabowski, P S; Reid, D M; Ralston, S H

1999-12-01

Inflammatory disease is associated with increased production of nitric oxide (NO) and activation of the inducible nitric oxide synthase (iNOS) pathway. Several studies have addressed the role of NO as a mediator of cytokine effects on bone cell activity in vitro. Stimulatory and inhibitory actions have been found, however, depending on the concentrations produced and model system used. In view of this, it has been difficult to predict whether increased production of NO during inflammation is likely to increase bone loss or prevent it. We have investigated the pathogenic role of NO in an animal model of inflammation-induced osteoporosis (IMO). NO production was increased in IMO when compared with controls (+344%; p turnover, but L-NMMA had no effect on bone mass in control animals. This study has important implications for many inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel disease which are associated with increased NO production and osteoporosis. Our data not only suggest that iNOS activation and increased NO production contribute to the pathogenesis of osteoporosis in these situations, but also suggest that NOS inhibitors could be of therapeutic value in the prevention and treatment of such bone loss.

Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

Directory of Open Access Journals (Sweden)

P Padmini S J Khedoe

Full Text Available COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD, and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L mice.Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study or in week 14, 16, 18 and 20 (chronic study. Inflammatory parameters were measured in bronchoalveolar lavage (BAL and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment.These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

Hypoxia-inducible factor-1α/interleukin-1β signaling enhances hepatoma epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory microenvironment.

Science.gov (United States)

Zhang, Jingying; Zhang, Qi; Lou, Yu; Fu, Qihan; Chen, Qi; Wei, Tao; Yang, Jiaqi; Tang, Jinlong; Wang, Jianxin; Chen, Yiwen; Zhang, Xiaoyu; Zhang, Jian; Bai, Xueli; Liang, Tingbo

2018-05-01

The development and progression of hepatocellular carcinoma (HCC) are dependent on its local microenvironment. Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood. We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α). Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype. We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation. Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion. Following the increase of IL-1β in the local microenvironment, the synthesis of HIF-1α was up-regulated by IL-1β in HCC cells through cyclooxygenase-2. The epithelial-mesenchymal transition of HCC cells was enhanced by overexpression of HIF-1α. We further showed that IL-1β promoted HCC metastasis in mouse models and was predictive of poor prognosis in HCC patients. Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment. (Hepatology 2018;67:1872-1889). © 2017 by the American Association for the Study of Liver

Gastrointestinal microbiota and local inflammation during oxazolone-induced dermatitis in BALB/cA Mice

DEFF Research Database (Denmark)

Lundberg, Randi; Knoth Clausen, Susanne; Pang, Wanyong

2012-01-01

-induced skin inflammation model of atopic dermatitis. BALB/cA mice were sensitized with oxazolone over a 28-d period and variation in gastrointestinal microbiota in fecal and cecal samples was assessed by PCR-denaturing gradient gel electrophoresis. Clinical parameters included transepidermal water loss, ear...

Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-γ-Driven Inflammation

Directory of Open Access Journals (Sweden)

Tiago Silva Medina

2017-09-01

Full Text Available The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-γ-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs, in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-γ blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease

Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-γ-Driven Inflammation

Science.gov (United States)

Medina, Tiago Silva; Oliveira, Gabriela Gonçalves; Silva, Maria Cláudia; David, Bruna Araújo; Silva, Grace Kelly; Fonseca, Denise Morais; Sesti-Costa, Renata; Frade, Amanda Farage; Baron, Monique Andrade; Ianni, Barbara; Pereira, Alexandre Costa; Chevillard, Christophe; Cunha-Neto, Edécio; Marin-Neto, José Antonio; Silva, João Santana

2017-01-01

The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT) and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-γ-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs), in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-γ blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease. Collectively, we

Orbital debris: a technical assessment

National Research Council Canada - National Science Library

Committee on Space Debris, National Research Council

..., and other debris created as a byproduct of space operations. Orbital Debris examines the methods we can use to characterize orbital debris, estimates the magnitude of the debris population, and assesses the hazard that this population poses to spacecraft...

Effects of positive end-expiratory pressure titration and recruitment maneuver on lung inflammation and hyperinflation in experimental acid aspiration-induced lung injury.

Science.gov (United States)

Ambrosio, Aline M; Luo, Rubin; Fantoni, Denise T; Gutierres, Claudia; Lu, Qin; Gu, Wen-Jie; Otsuki, Denise A; Malbouisson, Luiz M S; Auler, Jose O C; Rouby, Jean-Jacques

2012-12-01

In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

Protective effect of Korean Red Ginseng extract against Helicobacter pylori-induced gastric inflammation in Mongolian gerbils

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Minkyung Bae

2014-01-01

Full Text Available Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL-8 and inducible nitric oxide synthase (iNOS, which are mediated by oxidant-sensitive transcription factor NF-κB. High levels of lipid peroxide (LPO and increased activity of myeloperoxidase (MPO, a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog, IL-1β, and iNOS; protein level of phospho-IκBα (which reflects the activation of NF-κB; and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-1β, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of IκBα and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of polymorphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pylori-induced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-1β, iNOS, MPO activity, and LPO level in H. pylori-infected gastric mucosa.

Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

Science.gov (United States)

Phillips, Matthew C; Dheer, Rishu; Santaolalla, Rebeca; Davies, Julie M; Burgueño, Juan; Lang, Jessica K; Toborek, Michal; Abreu, Maria T

2018-01-15

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium. Copyright © 2017 Elsevier Inc. All rights reserved.

Debris filtering efficiency and its effect on long term cooling capability

International Nuclear Information System (INIS)

Jung, Min-Su; Kim, Kyu-Tae

2013-01-01

Highlights: • Debris filtering efficiencies for two debris filter designs used in PWRs are provided. • Various debris used in the tests are selected to simulate actual debris found in PWRs. • Debris filter efficiency is explained by flow-hole size and grid strap height. • The effect of debris filters on flow blockage during LTC after a LOCA is described. -- Abstract: A cutting-edge debris-filter designs, Protective Grid (P-grid) and Guardian Grid (G-grid) attached to the upper part of bottom nozzle, have been employed for the PWRs in Korea since 2000s to protect the fuel from debris-induced fuel failures. The debris-filter efficiency of the P-grid and G-grid designs is improved by relatively smaller flow areas formed by the grid straps and dimples. The debris-filter efficiency of the P-grid design is further improved by the relatively smaller flow-hole bottom nozzle. The debris-filter flow tests employing eighteen debris types showed that the debris-filter efficiencies of the P-grid and G-grid designs are 91 and 96%, respectively, while that of the SYS80 fuel design having only the standard flow-hole bottom nozzle is 26%. The slightly better debris-filter efficiency of the G-grid design against the P-grid design may be explained by relatively smaller flow areas at the G-grid dimple region as well as by the relatively longer solid end plug and the higher G-grid strap. The P-grid design may capture circular shapes of debris larger than 3.44 mm in diameter at the flow holes formed by the P-grid dimples, whereas the G-grid design may capture circular shapes of debris larger than 2.54 mm in diameter at the flow holes formed by the G-grid dimples. The aforementioned difference in the debris-filter efficiency between the P-grid and G-grid designs may be predicted by the solid modeling technique generating three-dimensional flow paths. Using the minimum flow-hole areas generated by the P-grid and G-grid designs, on the other hand, the effect of debris injected from

Histopathological Analysis of PEEK Wear Particle Effects on the Synovial Tissue of Patients

Science.gov (United States)

Jansson, V.; Giurea, A.

2016-01-01

Introduction. Increasing interest developed in the use of carbon-fiber-reinforced-poly-ether-ether-ketones (CFR-PEEK) as an alternative bearing material in knee arthroplasty. The effects of CFR-PEEK wear in in vitro and animal studies are controversially discussed, as there are no data available concerning human tissue. The aim of this study was to analyze human tissue containing CFR-PEEK as well as UHMWPE wear debris. The authors hypothesized no difference between the used biomaterials. Methods and Materials. In 10 patients during knee revision surgery of a rotating-hinge-knee-implant-design, synovial tissue samples were achieved (tibial inserts: UHMWPE; bushings and flanges: CFR-PEEK). One additional patient received revision surgery without any PEEK components as a control. The tissue was paraffin-embedded, sliced into 2 μm thick sections, and stained with hematoxylin and eosin in a standard process. A modified panoptical staining was also done. Results. A “wear-type” reaction was seen in the testing and the control group. In all samples, the UHMWPE particles were scattered in the tissue or incorporated in giant cells. CFR-PEEK particles were seen as conglomerates and only could be found next to vessels. CFR-PEEK particles showed no giant-cell reactions. In conclusion, the hypothesis has to be rejected. UHMWPE and PEEK showed a different scatter-behavior in human synovial tissue. PMID:27766256

Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice.

Directory of Open Access Journals (Sweden)

Haiya Wu

Full Text Available CFTR (cystic fibrosis transmembrane conductance regulator is expressed by both neutrophils and platelets. Lack of functional CFTR could lead to severe lung infection and inflammation. Here, we found that mutation of CFTR (F508del or inhibition of CFTR in mice led to more severe thrombocytopenia, alveolar neutrocytosis and bacteriosis, and lower lipoxin A4/MIP-2 (macrophage inhibitory protein-2 or lipoxin A4/neutrophil ratios in the BAL (bronchoalveolar lavage during acute E. coli pneumonia. In vitro, inhibition of CFTR promotes MIP-2 production in LPS-stimulated neutrophils; however, lipoxin A4 could dose-dependently suppress this effect. In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1 or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice. Concurrently, F508del mice had higher plasma platelet activating factor (PAF levels and PAF-AH activity compared to wildtype under LPS challenge. Inhibiting hydrolysis of PAF by a specific PAF-AH (PAF-acetylhydrolase inhibitor, MAFP, could worsen LPS-induced lung inflammation in F508del mice compared to vehicle treated F508del group. Particularly, depletion of platelets in F508del mice could significantly decrease plasma lipoxin A4 and PAF-AH activity and deteriorate LPS-induced lung inflammation compared to control F508del mice. Taken together, lipoxin A4 and PAF are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice, suggesting that lipoxin A4 and PAF might be therapeutic targets for ameliorating CFTR-deficiency deteriorated lung inflammation.

Application of Influence Function Method to the Fretting Wear Problems

Energy Technology Data Exchange (ETDEWEB)

Lee, Choon Yeol; Tian, Li Si; Bae, Joon Woo; Chai, Young Suck [Yeungnam University, Gyongsan (Korea, Republic of)

2006-07-01

Numerical analysis by influence function method (IFM) is demonstrated in this study in order to investigate the fretting wear problems on the secondary side of the steam generator, caused by flow induced vibration. Two-dimensional numerical contact model in terms of Cauchy integral equation is developed. The distributions of normal pressures, shear stresses and displacement fields are derived between two contact bodies which have similar elastic properties. The work rate model is adopted to find the wear amounts between two materials. The results are compared with the solutions by finite element analyses, which show the utilization of the present method to the fretting wear problems.

Application of Influence Function Method to the Fretting Wear Problems

International Nuclear Information System (INIS)

Lee, Choon Yeol; Tian, Li Si; Bae, Joon Woo; Chai, Young Suck

2006-01-01

Numerical analysis by influence function method (IFM) is demonstrated in this study in order to investigate the fretting wear problems on the secondary side of the steam generator, caused by flow induced vibration. Two-dimensional numerical contact model in terms of Cauchy integral equation is developed. The distributions of normal pressures, shear stresses and displacement fields are derived between two contact bodies which have similar elastic properties. The work rate model is adopted to find the wear amounts between two materials. The results are compared with the solutions by finite element analyses, which show the utilization of the present method to the fretting wear problems

A Feasibility Study on the Worn Area Estimation by Measuring a Contact Resistance (I)

International Nuclear Information System (INIS)

Lee, Young-Ho; Kim, Hyung-Kyu

2007-01-01

In order to improve the fretting wear resistance of the nuclear fuel rod with considering the effect of the contacting spring shape, it is necessary to examine the formation procedure of the worn area during the fretting wear experiments with including its shape, size and the debris removal path. This is because the wear volume and the maximum wear depth are dominantly affected by the worn area and the wear resistance of the nuclear fuel rod was dominantly affected by the spring shape rather than the test environment and the contact mode (i.e. impact, sliding, rubbing, etc.). Unfortunately, it is almost impossible to archive the size and shape of the worn area on real-time basis because the contact surfaces are always hidden. If we could measure the worn area properties during fretting wear tests, it enables us to promptly estimate the wear resistance or behavior with various contacting spring shapes. Generally, fretting wear degradation is generated by the localized plastic deformation, fracture and finally detachment of wear debris. Generally, wear debris easily oxidized by frictional heat, test environment, etc. From the previous studies, most of the wear debris was detached from the worn surface in the distilled water condition while the wear debris in the dry condition remained on or adhered to the worn surface. At this time, it is reasonable that the accumulated wear debris on the worn surface is existed in the form of oxide. If small amount of electric current was applied between the contacting surfaces, wear debris could be an obstacle to flow the electric current. This means that the variation of the contact resistance under constant electric current during the fretting wear tests has much information on the formation of the worn area even though the applying current could accelerate the oxidation of the generated wear debris. So, in this study, fretting wear tests have been performed with applying an electric current in room temperature air in order to

Gomisin N ameliorates lipopolysaccharide-induced depressive-like behaviors by attenuating inflammation in the hypothalamic paraventricular nucleus and central nucleus of the amygdala in mice

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Ryota Araki

2016-10-01

Full Text Available Emotional impairments such as depressive symptoms often develop in patients with sustained and systemic immune activation. The objective of this study is to investigate the effect of gomisin N, a dibenzocyclooctadiene lignan isolated from the dried fruits of Schisandra chinensis (Turcz. Baill., which exhibited inhibitory effects of the bacterial endotoxin lipopolysaccharide (LPS-induced NO production in a screening assay, on inflammation-induced depressive symptoms. We examined the effects of gomisin N on inflammation induced by LPS in murine microglial BV-2 cells and on LPS-induced behavioral changes in mice. Gomisin N inhibited LPS-induced expression of mRNAs for inflammation-related genes (inducible nitric oxide synthase (iNOS, cyclooxygenase (COX-2, interleukin (IL-1β, IL-6 and tumor necrosis factor (TNF-α in BV-2 cells. Administration of gomisin N attenuated LPS-induced expression of mRNAs for inflammation-related genes, increases in the number of c-Fos immunopositive cells in the hypothalamus and amygdala, depressive-like behavior in the forced swim test and exploratory behavior deficits 24 h after LPS administration in mice. These results suggest that gomisin N might ameliorate LPS-induced depressive-like behaviors through inhibition of inflammatory responses and neural activation in the hypothalamus and amygdala.

Effect of cup inclination on predicted contact stress-induced volumetric wear in total hip replacement.

Science.gov (United States)

Rijavec, B; Košak, R; Daniel, M; Kralj-Iglič, V; Dolinar, D

2015-01-01

In order to increase the lifetime of the total hip endoprosthesis, it is necessary to understand mechanisms leading to its failure. In this work, we address volumetric wear of the artificial cup, in particular the effect of its inclination with respect to the vertical. Volumetric wear was calculated by using mathematical models for resultant hip force, contact stress and penetration of the prosthesis head into the cup. Relevance of the dependence of volumetric wear on inclination of the cup (its abduction angle ϑA) was assessed by the results of 95 hips with implanted endoprosthesis. Geometrical parameters obtained from standard antero-posterior radiographs were taken as input data. Volumetric wear decreases with increasing cup abduction angle ϑA. The correlation within the population of 95 hips was statistically significant (P = 0.006). Large cup abduction angle minimises predicted volumetric wear but may increase the risk for dislocation of the artificial head from the cup in the one-legged stance. Cup abduction angle and direction of the resultant hip force may compensate each other to achieve optimal position of the cup with respect to wear and dislocation in the one-legged stance for a particular patient.

SOCS3 Expression Correlates with Severity of Inflammation, Expression of Proinflammatory Cytokines, and Activation of STAT3 and p38 MAPK in LPS-Induced Inflammation In Vivo

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João Antônio Chaves de Souza

2013-01-01

Full Text Available SOCS3 is an inducible endogenous negative regulator of JAK/STAT pathway, which is relevant in inflammatory conditions. We used a model of LPS-induced periodontal disease in rats to correlate SOCS3 expression with the inflammatory status. In vitro we used a murine macrophage cell line to assess the physical interaction between SOCS3 and STAT3 by coimmunoprecipitation. 30 ug of LPS from Escherichia coli were injected in the gingival tissues on the palatal aspect of first molars of the animals 3x/week for up to 4 weeks. Control animals were injected with the vehicle (PBS. The rats were sacrificed at 7, 15, and 30 days. Inflammation and gene expression were assessed by stereometric analysis, immunohistochemistry, RT-qPCR, and western blot. LPS injections increased inflammation, paralleled by an upregulation of SOCS3, of the proinflammatory cytokines IL-1β, IL-6, and TNF-α and increased phosphorylation of STAT3 and p38 MAPK. SOCS3 expression accompanied the severity of inflammation and the expression of proinflammatory cytokines, as well as the activation status of STAT3 and p38 MAPK. LPS stimulation in a macrophage cell line in vitro induced transient STAT3 activation, which was inversely correlated with a dynamic physical interaction with SOCS3, suggesting that this may be a mechanism for SOCS3 regulatory function.

Characterization of holding brake friction pad surface after pin-on-plate wear test

DEFF Research Database (Denmark)

Drago, N.; Gonzalez Madruga, D.; De Chiffre, L.

2018-01-01

This article concerns the metrological characterization of the surface on a holding brake friction material pin after a pin-on-plate (POP) wear test. The POP test induces the formation of surface plateaus that affect brake performances such as wear, friction, noise and heat. Three different...

Superior sealing effect of hydroxyapatite in porous-coated implants

DEFF Research Database (Denmark)

Rahbek, Ole; Kold, Søren; Bendix, Knud

2005-01-01

Migration of wear debris to the periprosthetic bone is a major cause of osteolysis and implant failure. Both closed-pore porous coatings and hydroxyapatite (HA) coatings have been claimed to prevent the migration of wear debris. We investigated whether HA could augment the sealing effect of a por......Migration of wear debris to the periprosthetic bone is a major cause of osteolysis and implant failure. Both closed-pore porous coatings and hydroxyapatite (HA) coatings have been claimed to prevent the migration of wear debris. We investigated whether HA could augment the sealing effect...

GSK-3β Inhibition Attenuates CLP-Induced Liver Injury by Reducing Inflammation and Hepatic Cell Apoptosis

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Hui Zhang

2014-01-01

Full Text Available Liver dysfunction has been known to occur frequently in cases of sepsis. Excessive inflammation and apoptosis are pathological features of acute liver failure. Recent studies suggest that activation of glycogen synthase kinase- (GSK- 3β is involved in inflammation and apoptosis. We aimed to investigate the protective effects of GSK-3β inhibition on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP, and SB216763 was used to inhibit GSK-3β in C57BL/6 mice. GSK-3β was activated following CLP. Administration of SB216763 decreased mortality, ameliorated liver injury, and reduced hepatic apoptosis. The inhibition of GSK-3β also reduced leukocyte infiltration and hepatic inflammatory cytokine expression and release. Moreover, GSK-3β inhibition suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB but enhanced the transcriptional activity of cAMP response element binding protein (CREB in the liver. In in vitro studies, GSK-3β inhibition reduced inflammatory cytokine production via modulation of NF-κB and CREB signaling pathways in lipopolysaccharide-stimulated macrophages. In conclusion, these findings suggest that GSK-3β blockade protects against CLP-induced liver via inhibition of inflammation by modulating NF-κB and CREB activity and suppression of hepatic apoptosis.

Chlorpromazine-induced hepatotoxicity during inflammation is mediated by TIRAP-dependent signaling pathway in mice

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Gandhi, Adarsh; Guo, Tao; Shah, Pranav; Moorthy, Bhagavatula; Ghose, Romi

2013-01-01

Inflammation is a major component of idiosyncratic adverse drug reactions (IADRs). To understand the molecular mechanism of inflammation-mediated IADRs, we determined the role of the Toll-like receptor (TLR) signaling pathway in idiosyncratic hepatotoxicity of the anti-psychotic drug, chlorpromazine (CPZ). Activation of TLRs recruits the first adaptor protein, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) to the TIR domain of TLRs leading to the activation of the downstream kinase, c-Jun-N-terminal kinase (JNK). Prolonged activation of JNK leads to cell-death. We hypothesized that activation of TLR2 by lipoteichoic acid (LTA) or TLR4 by lipopolysaccharide (LPS) will augment the hepatotoxicity of CPZ by TIRAP-dependent mechanism involving prolonged activation of JNK. Adult male C57BL/6, TIRAP +/+ and TIRAP −/− mice were pretreated with saline, LPS (2 mg/kg) or LTA (6 mg/kg) for 30 min or 16 h followed by CPZ (5 mg/kg) or saline (vehicle) up to 24 h. We found that treatment of mice with CPZ in presence of LPS or LTA leads to ∼ 3–4 fold increase in serum ALT levels, a marked reduction in hepatic glycogen content, significant induction of serum tumor necrosis factor (TNF) α and prolonged JNK activation, compared to LPS or LTA alone. Similar results were observed in TIRAP +/+ mice, whereas the effects of LPS or LTA on CPZ-induced hepatotoxicity were attenuated in TIRAP −/− mice. For the first time, we show that inflammation-mediated hepatotoxicity of CPZ is dependent on TIRAP, and involves prolonged JNK activation in vivo. Thus, TIRAP-dependent pathways may be targeted to predict and prevent inflammation-mediated IADRs. -- Highlights: ► Inflammation augments the toxicity of an idiosyncratic hepatotoxin chlorpromazine. ► Activation of Toll-like receptors by LPS or LTA induces chlorpromazine toxicity. ► Sustained stress kinase (JNK) activation is associated with chlorpromazine toxicity. ► These studies provide novel mechanistic

Chlorpromazine-induced hepatotoxicity during inflammation is mediated by TIRAP-dependent signaling pathway in mice

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Gandhi, Adarsh, E-mail: adarsh.gandhi@nih.gov [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Guo, Tao, E-mail: tguo4@jhu.edu [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Shah, Pranav [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Baylor College of Medicine, Department of Pediatrics, 1102 Bates Avenue, Suite 530, Houston, TX 77030 (United States); Ghose, Romi, E-mail: rghose@uh.edu [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States)

2013-02-01

Inflammation is a major component of idiosyncratic adverse drug reactions (IADRs). To understand the molecular mechanism of inflammation-mediated IADRs, we determined the role of the Toll-like receptor (TLR) signaling pathway in idiosyncratic hepatotoxicity of the anti-psychotic drug, chlorpromazine (CPZ). Activation of TLRs recruits the first adaptor protein, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) to the TIR domain of TLRs leading to the activation of the downstream kinase, c-Jun-N-terminal kinase (JNK). Prolonged activation of JNK leads to cell-death. We hypothesized that activation of TLR2 by lipoteichoic acid (LTA) or TLR4 by lipopolysaccharide (LPS) will augment the hepatotoxicity of CPZ by TIRAP-dependent mechanism involving prolonged activation of JNK. Adult male C57BL/6, TIRAP{sup +/+} and TIRAP{sup −/−} mice were pretreated with saline, LPS (2 mg/kg) or LTA (6 mg/kg) for 30 min or 16 h followed by CPZ (5 mg/kg) or saline (vehicle) up to 24 h. We found that treatment of mice with CPZ in presence of LPS or LTA leads to ∼ 3–4 fold increase in serum ALT levels, a marked reduction in hepatic glycogen content, significant induction of serum tumor necrosis factor (TNF) α and prolonged JNK activation, compared to LPS or LTA alone. Similar results were observed in TIRAP{sup +/+} mice, whereas the effects of LPS or LTA on CPZ-induced hepatotoxicity were attenuated in TIRAP{sup −/−} mice. For the first time, we show that inflammation-mediated hepatotoxicity of CPZ is dependent on TIRAP, and involves prolonged JNK activation in vivo. Thus, TIRAP-dependent pathways may be targeted to predict and prevent inflammation-mediated IADRs. -- Highlights: ► Inflammation augments the toxicity of an idiosyncratic hepatotoxin chlorpromazine. ► Activation of Toll-like receptors by LPS or LTA induces chlorpromazine toxicity. ► Sustained stress kinase (JNK) activation is associated with chlorpromazine toxicity. ► These studies

Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

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Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu

2013-10-15

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.

Soyabean oil supplementation effects on perivascular inflammation in lungs induced by bisphenol a: a histological study

International Nuclear Information System (INIS)

Shaukat, S.; Hamid, S.; Umbreen, F.

2017-01-01

To determine the effect of soyabean oil supplementation on perivascular inflammation in lungs of adult mice induced by Bisphenol A (BPA). Study Design: An experimental study. Place and Duration of Study: Department of Anatomy, Army Medical College, Rawalpindi, in collaboration with the Animal House, National Institute of Health, Islamabad, from June to November 2016. Methodology:Thirty male and female BALB/c mice were divided into three groups, of 10 animals each. Group A animals served as control. Group B animals were given BPA at a dose of 50 mg/Kg body weight/day. Group C animals were given BPA and soyabean oil at doses of 50 mg/Kg body weight/day and 500 mg/day, respectively. All treatments were given once daily for a period of eight weeks. Animals were dissected 24 hours after receiving the last dose. Lung tissue specimen processing and H and E staining was carried out for routine histological study. Perivascular inflammation was morphometrically graded and statistically analysed using Chi-square test with p<0.05. Results: Grade 2 inflammation was recorded in two (20%) animals and grade 3 perivascular inflammation in 80% specimens in Group B; whereas 20% specimens of Group C had grade 2 inflammation and eight (80%) showed grade 1 inflammation. None of the control animals showed any inflammation. All groups were significantly different at p<0.001. Conclusion: BPA produced perivascular inflammation and con-commitant administration of soyabean oil diet protected against it in rodent. (author)

The LIM-only protein FHL2 attenuates lung inflammation during bleomycin-induced fibrosis.

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Abdulaleem Alnajar

Full Text Available Fibrogenesis is usually initiated when regenerative processes have failed and/or chronic inflammation occurs. It is characterised by the activation of tissue fibroblasts and dysregulated synthesis of extracellular matrix proteins. FHL2 (four-and-a-half LIM domain protein 2 is a scaffolding protein that interacts with numerous cellular proteins, regulating signalling cascades and gene transcription. It is involved in tissue remodelling and tumour progression. Recent data suggest that FHL2 might support fibrogenesis by maintaining the transcriptional expression of alpha smooth muscle actin and the excessive synthesis and assembly of matrix proteins in activated fibroblasts. Here, we present evidence that FHL2 does not promote bleomycin-induced lung fibrosis, but rather suppresses this process by attenuating lung inflammation. Loss of FHL2 results in increased expression of the pro-inflammatory matrix protein tenascin C and downregulation of the macrophage activating C-type lectin receptor DC-SIGN. Consequently, FHL2 knockout mice developed a severe and long-lasting lung pathology following bleomycin administration due to enhanced expression of tenascin C and impaired activation of inflammation-resolving macrophages.

Comparison of Apical Extrusion of Debris by Using Single-File, Full-Sequence Rotary and Reciprocating Systems

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Maryam Ehsani

2017-01-01

Full Text Available Objectives: During root canal preparation, apical extrusion of debris can cause inflammation, flare-ups, and delayed healing. Therefore, instrumentation techniques that cause the least extrusion of debris are desirable. This study aimed to compare apical extrusion of debris by five single-file, full-sequence rotary and reciprocating systems.Materials and Methods: One hundred twenty human mandibular premolars with similar root lengths, apical diameters, and canal curvatures were selected and randomly assigned to six groups (n=20: Reciproc R25 (25, 0.08, WaveOne Primary (25, 0.08, OneShape (25, 0.06, F360 (25, 0.04, Neoniti A1 (25, 0.08, and ProTaper Universal. Instrumentation of the root canals was performed in accordance with the manufacturers’ instructions. Each tooth's debris was collected in a pre-weighed vial. After drying the debris in an incubator, the mass was measured three times consecutively; the mean was then calculated. The preparation time by each system was also measured. For data analysis, one-way ANOVA and Games-Howell post hoc test were used.Results: The mean masses (±standard deviation of the apical debris were as follows: 2.071±1.38mg (ProTaper Universal, 1.702±1.306mg (Neoniti A1, 1.295±0.839mg (OneShape, 1.109±0.676mg (WaveOne, 0.976±0.478mg (Reciproc and 0.797±0.531mg (F360. Compared to ProTaper Universal, F360 generated significantly less debris (P=0.02. The ProTaper system required the longest preparation time (mean=88.6 seconds; the Reciproc (P=0.008, OneShape (P=0.006, and F360 (P=0.001 required significantly less time (P<0.05.Conclusions: All instruments caused extrusion of debris through the apex. The F360 produced significantly less debris than did the ProTaper Universal.Keywords: Dentistry; Endodontics; Root Canal Preparation; Instrumentation

Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation.

Science.gov (United States)

Sempértegui, Fernando; Díaz, Myriam; Mejía, Ricardo; Rodríguez-Mora, Oswaldo G; Rentería, Edgar; Guarderas, Carlos; Estrella, Bertha; Recalde, Ramiro; Hamer, Davidson H; Reeves, Philip G

2007-02-01

Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations.

Woody debris

Science.gov (United States)

Donna B. Scheungrab; Carl C. Trettin; Russ Lea; Martin F. Jurgensen

2000-01-01

Woody debris can be defined as any dead, woody plant material, including logs, branches, standing dead trees, and root wads. Woody debris is an important part of forest and stream ecosystems because it has a role in carbon budgets and nutrient cycling, is a source of energy for aquatic ecosystems, provides habitat for terrestrial and aquatic organisms, and contributes...

Anti-hyperalgesic and anti-inflammatory effects of Achillea santolina and Stachys athorecalyx extracts on complete Freund's adjuvant–induced short- term inflammation in male wistar rats

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Elaheh Tekieh

2011-04-01

Full Text Available Introduction: Immune system is involved in the etiology and path physiologic mechanisms of inflammation. Medicinal plants are an important source of substances which are claimed to induce non-specific immune modulator effects. Given the above information and the role of IL-6 in inflammation and pain induction, this study investigated the effects of Achillea santolina and Stachys athorecalyx methanolic and defatted extracts on cmplete Freund's adjuvant (CFA -induced short term inflammation in male Wistar rats Materials and Methods: Inflammation was induced on day zero by CFA injection in hind paw of rats. Methanolic and defatted extractions were prepared form aerial parts of both plants. 50, 100 and 200 mg/kg doses of extracts were selected for IP treatment during 6 days after CFA injection. Results: Results indicated dose related effects of A. santolina and S. athorecalyx extracts on edema, hyperalgesia and serum IL-6 level during inflammation. Although, both methanolic and defatted extracts of S. athorecalyx showed a significant reduction in the inflammatory symptoms, no significant differences was observed between these two kinds of extracts of S.athorecalyx with respect to their anti inflammatory effects. Only methanolic extract of A. santolina was effective during CFA-induced inflammation. Conclusion: These results could suggest that short-term administration of A. santolina and S. athorecalyx extracts possess potent anti-inflammatory effects and modulate paw edema, hyperalgesia and serum IL-6 level during CFA–induced inflammation. In addition, these dose-dependent effects may mediate via different extract supplements which need more investigations.

Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation.

Science.gov (United States)

Desai, Harsh R; Sivasubramaniyam, Tharini; Revelo, Xavier S; Schroer, Stephanie A; Luk, Cynthia T; Rikkala, Prashanth R; Metherel, Adam H; Dodington, David W; Park, Yoo Jin; Kim, Min Jeong; Rapps, Joshua A; Besla, Rickvinder; Robbins, Clinton S; Wagner, Kay-Uwe; Bazinet, Richard P; Winer, Daniel A; Woo, Minna

2017-08-09

During obesity, macrophages can infiltrate metabolic tissues, and contribute to chronic low-grade inflammation, and mediate insulin resistance and diabetes. Recent studies have elucidated the metabolic role of JAK2, a key mediator downstream of various cytokines and growth factors. Our study addresses the essential role of macrophage JAK2 in the pathogenesis to obesity-associated inflammation and insulin resistance. During high-fat diet (HFD) feeding, macrophage-specific JAK2 knockout (M-JAK2 -/- ) mice gained less body weight compared to wildtype littermate control (M-JAK2 +/+ ) mice and were protected from HFD-induced systemic insulin resistance. Histological analysis revealed smaller adipocytes and qPCR analysis showed upregulated expression of some adipogenesis markers in visceral adipose tissue (VAT) of HFD-fed M-JAK2 -/- mice. There were decreased crown-like structures in VAT along with reduced mRNA expression of some macrophage markers and chemokines in liver and VAT of HFD-fed M-JAK2 -/- mice. Peritoneal macrophages from M-JAK2 -/- mice and Jak2 knockdown in macrophage cell line RAW 264.7 also showed lower levels of chemokine expression and reduced phosphorylated STAT3. However, leptin-dependent effects on augmenting chemokine expression in RAW 264.7 cells did not require JAK2. Collectively, our findings show that macrophage JAK2 deficiency improves systemic insulin sensitivity and reduces inflammation in VAT and liver in response to metabolic stress.

Tofacitinib restores the inhibition of reverse cholesterol transport induced by inflammation: understanding the lipid paradox associated with rheumatoid arthritis.

Science.gov (United States)

Pérez-Baos, S; Barrasa, J I; Gratal, P; Larrañaga-Vera, A; Prieto-Potin, I; Herrero-Beaumont, G; Largo, R

2017-09-01

Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The JAK inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analysed the effect of tofacitinib on the lipid profile of hyperlipidaemic rabbits with chronic arthritis (CA) and on the changes in reverse cholesterol transport (RCT) during chronic inflammation. CA was induced in previously immunized rabbits, fed a high-fat diet, by administering four intra-articular injections of ovalbumin. A group of rabbits received tofacitinib (10 mg·kg -1 ·day -1 ) for 2 weeks. Systemic and synovial inflammation and lipid content were evaluated. For in vitro studies, THP-1-derived macrophages were exposed to high lipid concentrations and then stimulated with IFNγ in the presence or absence of tofacitinib in order to study mediators of RCT. Tofacitinib decreased systemic and synovial inflammation and increased circulating lipid levels. Although it did not modify synovial macrophage density, it reduced the lipid content within synovial macrophages. In foam macrophages in culture, IFNγ further stimulated intracellular lipid accumulation, while the JAK/STAT inhibition provoked by tofacitinib induced lipid release by increasing the levels of cellular liver X receptor α and ATP-binding cassette transporter (ABCA1) synthesis. Active inflammation could be associated with lipid accumulation within macrophages of CA rabbits. JAK inhibition induced lipid release through RCT activation, providing a plausible explanation for the effect of tofacitinib on the lipid profile of RA patients. © 2017 The British Pharmacological Society.

The Biologic Response to Polyetheretherketone (PEEK) Wear Particles in Total Joint Replacement: A Systematic Review.

Science.gov (United States)

Stratton-Powell, Ashley A; Pasko, Kinga M; Brockett, Claire L; Tipper, Joanne L

2016-11-01

Polyetheretherketone (PEEK) and its composites are polymers resistant to fatigue strain, radiologically transparent, and have mechanical properties suitable for a range of orthopaedic applications. In bulk form, PEEK composites are generally accepted as biocompatible. In particulate form, however, the biologic response relevant to joint replacement devices remains unclear. The biologic response to wear particles affects the longevity of total joint arthroplasties. Particles in the phagocytozable size range of 0.1 µm to 10 µm are considered the most biologically reactive, particularly particles with a mean size of PEEK-based wear debris from total joint arthroplasties. (1) What are the quantitative characteristics of PEEK-based wear particles produced by total joint arthroplasties? (2) Do PEEK wear particles cause an adverse biologic response when compared with UHMWPE or a similar negative control biomaterial? (3) Is the biologic response affected by particle characteristics? Embase and Ovid Medline databases were searched for studies that quantified PEEK-based particle characteristics and/or investigated the biologic response to PEEK-based particles relevant to total joint arthroplasties. The keyword search included brands of PEEK (eg, MITCH, MOTIS) or variations of PEEK types and nomenclature (eg, PAEK, CFR-PEEK) in combination with types of joint (eg, hip, knee) and synonyms for wear debris or immunologic response (eg, particles, cytotoxicity). Peer-reviewed studies, published in English, investigating total joint arthroplasty devices and cytotoxic effects of PEEK particulates were included. Studies investigating devices without articulating bearings (eg, spinal instrumentation devices) and bulk material or contact cytotoxicity were excluded. Of 129 studies, 15 were selected for analysis and interpretation. No studies were found that isolated and characterized PEEK wear particles from retrieved periprosthetic human tissue samples. In the four studies that

Haemophilus influenzae from Patients with Chronic Obstructive Pulmonary Disease Exacerbation Induce More Inflammation than Colonizers

Science.gov (United States)

Chin, Cecilia L.; Manzel, Lori J.; Lehman, Erin E.; Humlicek, Alicia L.; Shi, Lei; Starner, Timothy D.; Denning, Gerene M.; Murphy, Timothy F.; Sethi, Sanjay; Look, Dwight C.

2005-01-01

Rationale: Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Objective: To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD. Methods: Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells. Results: H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-κB and p38 mitogen-activated protein kinase signaling pathways. Conclusions: The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function. PMID:15805181

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

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Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

2016-04-29

Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

International Nuclear Information System (INIS)

Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

2016-01-01

Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

Wholesale debris removal from LEO

Science.gov (United States)

Levin, Eugene; Pearson, Jerome; Carroll, Joseph

2012-04-01

Recent advances in electrodynamic propulsion make it possible to seriously consider wholesale removal of large debris from LEO for the first time since the beginning of the space era. Cumulative ranking of large groups of the LEO debris population and general limitations of passive drag devices and rocket-based removal systems are analyzed. A candidate electrodynamic debris removal system is discussed that can affordably remove all debris objects over 2 kg from LEO in 7 years. That means removing more than 99% of the collision-generated debris potential in LEO. Removal is performed by a dozen 100-kg propellantless vehicles that react against the Earth's magnetic field. The debris objects are dragged down and released into short-lived orbits below ISS. As an alternative to deorbit, some of them can be collected for storage and possible in-orbit recycling. The estimated cost per kilogram of debris removed is a small fraction of typical launch costs per kilogram. These rates are low enough to open commercial opportunities and create a governing framework for wholesale removal of large debris objects from LEO.

The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury.

Science.gov (United States)

Puntorieri, Valeria; Hiansen, Josh Qua; McCaig, Lynda A; Yao, Li-Juan; Veldhuizen, Ruud A W; Lewis, James F

2013-11-20

Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation. Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours). For both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate. The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.

A State of the Art Report on Wear Damage of Steam Generator Tubes

International Nuclear Information System (INIS)

Lim, Yun Soo; Kim, Joung Soo; Kim, Hong Pyo; Hwang, Seong Sik; Jung, Man Kyo

2004-10-01

The recent status on wear damage of steam generator tubes caused by flow-induced vibration was investigated, and the criteria for structural integrity evaluation of the wear-damaged tubes were reviewed. It was surveyed how the wear damage of tubes could be affected by main parameters, such as, materials properties and their combination, impact load and vibration amplitude/frequency, contact areas and diametral clearance between the tube and tube support plate, wear test duration, and test temperature. Finally, corrosive wear, which means the combined action of corrosion and wear simultaneously, was also surveyed in this report. There has been only a few works concerned on the wear damage of steam generator tubes in Korea, compared with the leading foreign research institutes. Especially, the experience related to the wear characteristics of Alloy 690, which has become a replacement material for Alloy 600 as steam generator tubes, is far from satisfactory. Systematic studies, therefore, concerned with structural integrity of tubes as well as improvement of were resistance of Alloy 690 in the PWR environment are needed

Assessment of wear facets produced by the ACTA wear machine

DEFF Research Database (Denmark)

Benetti, Ana R; Larsen, Liselotte; Dowling, Adam H

2016-01-01

. The mean wear depth was measured using the traditionally employed 2D and compared with the 3D profilometric (digital) techniques. Data were submitted to analyses of variance, Tukey's post hoc tests and Independent Samples Student's t-tests (where appropriate) at p...OBJECTIVE: To investigate the use of a three-dimensional (3D) digital scanning method in determining the accuracy of the wear performance parameters of resin-based composites (RBCs) determined using a two-dimensional (2D) analogue methodology following in-vitro testing in an Academisch Centrum...... for Tandheelkunde Amsterdam (ACTA) wear machine. METHODS: Specimens compatible with the compartments of the ACTA wear machine specimen wheel (n=10) were prepared from one commercial and four experimental RBCs. The RBC specimens were rotated against an antagonist wheel in a food-like slurry for 220,000 wear cycles...

Polymer wear evaluation

DEFF Research Database (Denmark)

Lagerbon, Mikkel; Sivebæk, Ion Marius

2012-01-01

Polymer wear plays an increasing role in manufacturing of machine parts for e.g. medical devices. Some of these have an expected lifetime of five to eight years during which very little wear of the components is acceptable. Too much wear compromises the dosage accuracy of the device and thereby...... the safety of the patients. Prediction of the wear of polymers is complicated by the low thermal conductivity of this kind of material. It implies that any acceleration of testing conditions by increased contact pressure and/or sliding velocity will make the polymer fail due to exaggerated heat buildup....... This is not the kind of wear observed in medical devices. In the present work a method was developed capable of evaluating the wear progression in polymer-polymer contacts. The configuration of the setup is injection moulded specimens consisting of an upper part having a toroid shape and a lower flat part. The sliding...

Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation

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Abdulrahman Al Asmari

Full Text Available Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA, myeloperoxidase activity (MPO, expression of nuclear factor kappa B (NF-κB p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion (P < 0.001 and acidity (P < 0.0001 and gastric ulcer index scores (P < 0.001. and augmented the gastric mucosal defense. Vanillin significantly restored the depleted gastric wall mucus levels (P < 0.0001 induced by ethanol and also significantly attenuated ethanol induced inflammation and oxidative stress by the suppression of gastric MPO activity (P < 0.001, reducing the expression of NF-κB p65 and the increased MDA levels (P < 0.001. Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol.Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture. Keywords: Gastric ulcers, Pylorus ligation, Ethanol, Vanillin, Inflammation, Oxidative stress

Adiponectin protects palmitic acid induced endothelial inflammation and insulin resistance via regulating ROS/IKKβ pathways.

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Zhao, Wenwen; Wu, Chuanhong; Li, Shaojing; Chen, Xiuping

2016-12-01

Endothelial inflammation and insulin resistance (IR) has been closely associated with endothelial dysfunction. Adiponectin (APN), an adipocyte-secreted hormone from adipose tissues, showed cardioprotective effects. Here, the protective effect of APN on palmitic acid (PA)-induced endothelial inflammation and IR was investigated. Cultured human umbilical vein endothelial cells (HUVECs) were treated with PA without or without APN pretreatment. The expression of inflammatory cytokines TNF-α, IL-6, adhesion molecule ICAM-1 were determined by western blotting, ELISA, and real-time PCR. The protein expression and protein-protein interaction were determined by western blotting and immunoprecipitation. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) production were monitored with fluorescence probes. PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1 at protein and mRNA levels, which was significantly inhibited by APN. PA treatment caused increase of ROS generation, NOX2, p-IKKβ, p-IκBα, p-p65 expression, and p-IκBα-IKKβ interaction, which were all partly reversed by APN. ROS scavenger N-acetylcysteine (NAC) and NF-κB inhibitor PDTC showed similar effect on PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1. Furthermore, APN and NAC pretreatment restored PA-induced increase of p-IRS-1(S307), decrease of p-IRS-1(Tyr). In addition, insulin-triggered expression of p-IRS-1(Tyr), p-PI3K, p-AKT, p-eNOS and NO generation were inhibited by PA, which were also restored by both APN and NAC. These results suggested that APN ameliorated endothelial inflammation and IR through ROS/IKKβ pathway. This study shed new insights into the mechanisms of APN's cardiovascular protective effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

DEFF Research Database (Denmark)

Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

2015-01-01

Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...... expressions in blood leukocytes during equine acute LPS-induced systemic inflammation thoroughly characterized a highly regulated and dynamic innate immune response. These results provide new insights into the molecular mechanisms of equine systemic inflammation....

Abrasive wear of ceramic wear protection at ambient and high temperatures

Science.gov (United States)

Varga, M.; Adam, K.; Tumma, M.; Alessio, K. O.

2017-05-01

Ceramic wear protection is often applied in abrasive conditions due to their excellent wear resistance. This is especially necessary in heavy industries conveying large amounts of raw materials, e.g. in steel industry. Some plants also require material transport at high temperatures and velocities, making the need of temperature stable and abrasion resistant wear protection necessary. Various types and wear behaviour of ceramic protection are known. Hence, the goal of this study is to identify the best suitable ceramic materials for abrasive conditions in harsh environments at temperatures up to 950°C and severe thermal gradients. Chamottes, known for their excellent thermal shock resistance are compared to high abrasion resistant ceramic wear tiles and a cost efficient cement-bounded hard compound. Testing was done under high-stress three-body abrasion regime with a modified ASTM G65 apparatus enabling for investigations up to ~950°C. Thereto heated abrasive is introduced into the wear track and also preheated ceramic samples were used and compared to ambient temperature experiments. Results indicate a significant temperature influence on chamottes and the hard compound. While the chamottes benefit from temperature increase, the cement-bounded hard compound showed its limitation at abrasive temperatures of 950°C. The high abrasion resistant wear tiles represented the materials with the best wear resistance and less temperature influence in the investigated range.

Fuel rod-grid interaction wear: in-reactor tests (LWBR development program)

International Nuclear Information System (INIS)

Stackhouse, R.M.

1979-11-01

Wear of the Zircaloy cladding of LWBR irradiation test fuel rods, resulting from relative motion between rod and rod support contacts, is reported. Measured wear depths were small, 0.0 to 2.7 mils, but are important in fuel element behavior assessment because of the local loss of cladding thickness, as well as the effect on grid spring forces that laterally restrain the rods. An empirical wear analysis model, based on out-of-pile tests, is presented. The model was used to calculate the wear on the irradiation test fuel rods attributed to a combination of up-and-down motions resulting from power and pressure/temperature cycling of the test reactor, flow-induced vibrations, and assembly handling scratches. The calculated depths are generally deeper than the measured depths

Fault Wear by Damage Evolution During Steady-State Slip

Science.gov (United States)

Lyakhovsky, Vladimir; Sagy, Amir; Boneh, Yuval; Reches, Ze'ev

2014-11-01

Slip along faults generates wear products such as gouge layers and cataclasite zones that range in thickness from sub-millimeter to tens of meters. The properties of these zones apparently control fault strength and slip stability. Here we present a new model of wear in a three-body configuration that utilizes the damage rheology approach and considers the process as a microfracturing or damage front propagating from the gouge zone into the solid rock. The derivations for steady-state conditions lead to a scaling relation for the damage front velocity considered as the wear-rate. The model predicts that the wear-rate is a function of the shear-stress and may vanish when the shear-stress drops below the microfracturing strength of the fault host rock. The simulated results successfully fit the measured friction and wear during shear experiments along faults made of carbonate and tonalite. The model is also valid for relatively large confining pressures, small damage-induced change of the bulk modulus and significant degradation of the shear modulus, which are assumed for seismogenic zones of earthquake faults. The presented formulation indicates that wear dynamics in brittle materials in general and in natural faults in particular can be understood by the concept of a "propagating damage front" and the evolution of a third-body layer.

A Comparative Uptake Study of Multiplexed PET Tracers in Mice with Turpentine-Induced Inflammation

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Tingting Huang

2012-11-01

Full Text Available The potential value of multiplexed positron emission tomography (PET tracers in mice with turpentine-induced inflammation was evaluated and compared with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG for glucose metabolism imaging. These PET tracers included [18F]fluoromethylcholine ([18F]FCH for choline metabolism imaging, (S-[11C]methyl-D-cysteine ([11C]DMCYS for amino acid metabolism imaging, [11C]bis(zinc(II-dipicolylamine ([11C]DPA-Zn2+ for apoptosis imaging, 2-(4-N-[11C]-methylaminophenyl-6-hydroxybenzothiazole ([11C]PIB for β amyloid binding imaging, and [18F]fluoride (18F− for bone metabolism imaging. In mice with turpentine-induced inflammation mice, the biodistribution of all the tracers mentioned above at 5, 15, 30, 45, and 60 min postinjection was determined. Also, the time-course curves of the tracer uptake ratios for inflammatory thigh muscle (IM to normal uninflammatory thigh muscle (NM, IM to blood (BL, IM to brain (BR, and IM to liver (LI were acquired, respectively. Moreover, PET imaging with the tracers within 60 min postinjection on a clinical PET/CT scanner was also conducted. [18F]FDG and 18F− showed relatively higher uptake ratios for IM to NM, IM to BL, IM to BR, and IM to LI than [18F]FCH, [11C]DPA-Zn2+, [11C]DMCYS and [11C]PIB, which were highly consistent with the results delineated in PET images. The results demonstrate that 18F− seems to be a potential PET tracer for inflammation imaging. [18F]FCH and [11C]DMCYS, with lower accumulation in inflammatory tissue than [18F]FDG, are not good PET tracers for inflammation imaging. As a promising inflammatory tracer, the chemical structure of [11C]DPA-Zn2+ needs to be further optimized.

Finger millet arabinoxylan protects mice from high-fat diet induced lipid derangements, inflammation, endotoxemia and gut bacterial dysbiosis.

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Sarma, Siddhartha Mahadeva; Singh, Dhirendra Pratap; Singh, Paramdeep; Khare, Pragyanshu; Mangal, Priyanka; Singh, Shashank; Bijalwan, Vandana; Kaur, Jaspreet; Mantri, Shrikant; Boparai, Ravneet Kaur; Mazumder, Koushik; Bishnoi, Mahendra; Bhutani, Kamlesh Kumar; Kondepudi, Kanthi Kiran

2018-01-01

Arabinoxylan (AX), a non-starch polysaccharide extracted from cereals such as wheat, rice and millets, is known to impart various health promoting effects. Our earlier study suggested that finger millet (FM) could ameliorate high fat diet (HFD)-induced metabolic derangements. The present study is aimed to evaluate the effect of FM-AX supplementation, a key bioactive from finger millet, on HFD-induced metabolic and gut bacterial derangements. Male Swiss albino mice were fed with normal chow diet (NPD) or HFD (60%kcal from fat) for 10 weeks. FM-AX was orally supplemented at doses of 0.5 and 1.0g/kg bodyweight on every alternate day for 10 weeks. Glucose tolerance, serum hormones, hepatic lipid accumulation and inflammation, white adipose tissue marker gene expression, adipocyte size and inflammation; metagenomic alterations in cecal bacteria; cecal short chain fatty acids and colonic tight junction gene expressions were studied. FM-AX supplementation prevented HFD-induced weight gain, alerted glucose tolerance and serum lipid profile, hepatic lipid accumulation and inflammation. Hepatic and white adipose tissue gene expressions were beneficially modulated. Further, AX supplementation prevented metagenomic alterations in cecum; improved ileal and colonic health and overall prevented metabolic endotoxemia. Present work suggests that AX from finger millet can be developed as a nutraceutical for the management of HFD- induced obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Cudrania tricuspidata and Kaempferol in Endoplasmic Reticulum Stress-Induced Inflammation and Hepatic Insulin Resistance in HepG2 Cells.

Science.gov (United States)

Kim, Ok-Kyung; Jun, Woojin; Lee, Jeongmin

2016-01-21

In this study, we quantitated kaempferol in water extract from Cudrania tricuspidata leaves (CTL) and investigated its effects on endoplasmic reticulum (ER) stress-induced inflammation and insulin resistance in HepG2 cells. The concentration of kaempferol in the CTL was 5.07 ± 0.08 mg/g. The HepG2 cells were treated with 300 µg/mL of CTL, 500 µg/mL of CTL, 1.5 µg/mL of kaempferol or 2.5 µg/mL of kaempferol, followed immediately by stimulation with 100 nM of thapsigargin for ER stress induction for 24 h. There was a marked increase in the activation of the ER stress and inflammation response in the thapsigargin-stimulated control group. The CTL treatment interrupted the ER stress response and ER stress-induced inflammation. Kaempferol partially inhibited the ER stress response and inflammation. There was a significant increase in serine phosphorylation of insulin receptor substrate (IRS)-1 and the expression of C/EBPα and gluconeogenic genes in the thapsigargin-stimulated control group compared to the normal control. Both CTL and kaempferol suppressed serine phosphorylation of IRS-1, and the treatments did not interrupt the C/EBPα/gluconeogenic gene pathway. These results suggest that kaempferol might be the active compound of CTL and that it might protect against ER stress-induced inflammation and hyperglycemia.

Sea Cucumber Lipid-Soluble Extra Fraction Prevents Ovalbumin-Induced Allergic Airway Inflammation.

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Lee, Da-In; Kang, Shin Ae; Md, Anisuzzaman; Jeong, U-Cheol; Jin, Feng; Kang, Seok-Joong; Lee, Jeong-Yeol; Yu, Hak Sun

2018-01-01

In a previous study, our research group demonstrated that sea cucumber (Apostichopus japonicus) extracts ameliorated allergic airway inflammation through CD4 + CD25 + Foxp3 + T (regulatory T; Treg) cell activation and recruitment to the lung. In this study, we aimed to determine which components of sea cucumber contribute to the amelioration of airway inflammation. We used n-hexane fractionation to separate sea cucumber into three phases (n-hexane, alcohol, and solid) and evaluated the ability of each phase to elevate Il10 expression in splenocytes and ameliorate symptoms in mice with ovalbumin (OVA)/alum-induced asthma. Splenocytes treated with the n-hexane phase showed a significant increase in Il10 expression. In the n-hexane phase, 47 fatty acids were identified. Individual fatty acids that comprised at least 5% of the total fatty acids were 16:0, 16:1n-7, 18:0, 18:1n-7, 20:4n-6, and 20:5n-3 (eicosapentaenoic acid). After administering the n-hexane phase to mice with OVA/alum-induced asthma, their asthma symptoms were ameliorated. Several immunomodulatory effects were observed in the n-hexane phase-pretreated group, compared with a vehicle control group. First, eosinophil infiltration and goblet cell hyperplasia were significantly reduced around the airways. Second, the concentrations of Th2-related cytokines (IL-4, IL-5, and IL-13) and Th17-related cytokines (IL-17) were significantly decreased in the spleen and bronchoalveolar lavage fluid (BALF). Finally, the concentrations of TGF-β and IL-10, which are associated with Treg cells, were significantly increased in the BALF and splenocyte culture medium. In conclusion, a fatty acid-rich fraction (n-hexane phase) of sea cucumber extract ameliorated allergic airway inflammation in a mouse model.

Regulatory T Cells Contribute to the Inhibition of Radiation-Induced Acute Lung Inflammation via Bee Venom Phospholipase A₂ in Mice.

Science.gov (United States)

Shin, Dasom; Lee, Gihyun; Sohn, Sung-Hwa; Park, Soojin; Jung, Kyung-Hwa; Lee, Ji Min; Yang, Jieun; Cho, Jaeho; Bae, Hyunsu

2016-04-30

Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase A₂ (bvPLA₂) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLA₂ in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLA₂ six times after radiation. To evaluate the level of inflammation, the number of immune cells, mRNA level of inflammatory cytokine, and histological changes in the lung were measured. BvPLA₂ treatment reduced the accumulation of immune cells, such as macrophages, neutrophils, lymphocytes, and eosinophils. In addition, bvPLA₂ treatment decreased inflammasome-, chemokine-, cytokine- and fibrosis-related genes' mRNA expression. The histological results also demonstrated the attenuating effect of bvPLA₂ on radiation-induced lung inflammation. Furthermore, regulatory T cell depletion abolished the therapeutic effects of bvPLA₂ in radiation-induced pneumonitis, implicating the anti-inflammatory effects of bvPLA₂ are dependent upon regulatory T cells. These results support the therapeutic potential of bvPLA₂ in radiation pneumonitis and fibrosis treatments.

Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice.

Science.gov (United States)

Liu, Zhaoguo; Zhu, Pingting; Tao, Yu; Shen, Cunsi; Wang, Siliang; Zhao, Lingang; Wu, Hongyan; Fan, Fangtian; Lin, Chao; Chen, Chen; Zhu, Zhijie; Wei, Zhonghong; Sun, Lihua; Liu, Yuping; Wang, Aiyun; Lu, Yin

2015-07-01

Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.