WorldWideScience

Sample records for ccl daresbury laboratory

  1. Beam tomography research at Daresbury Laboratory

    International Nuclear Information System (INIS)

    Beam tomography research at Daresbury Laboratory has focussed on the development of normalised phase space techniques—starting with the idea of sampling tomographic projections at equal phase advances. This idea has influenced the design and operation of the tomography sections at the Photo Injector Test Facility at Zeuthen (PITZ) and at the Accelerator and Lasers in Combined Experiments (ALICE) at Daresbury. We have studied the feasibility of using normalised phase space to measure the effect of space charge. Quadrupole scan measurements are carried out at two different parts of a beamline. Reconstructions at the same location give results that are clearly rotated with respect to each other in normalised phase space. We are able to show that a significant part of this rotation can be attributed to the effect of space charge. We show how the normalised phase space technique can be used to increase the reliability of the Maximum Entropy Technique (MENT). While MENT is known for its ability to work with just a few projections, the accuracy of its reconstructions has seldom been questioned. We show that for typical phase space distributions, MENT could produce results that look quite different from the original. We demonstrate that a normalised phase space technique could give results that are closer to the actual distribution. We also present simpler ways of deriving the phase space tomography formalism and the Maximum Entropy Technique

  2. The Daresbury Laboratory 1993/1994

    International Nuclear Information System (INIS)

    The scientific programme based on the Synchrotron Radiation Source (SRS) has continued in 1993/94 to be at the centre of the Daresbury Laboratory's work. The wide range of research in materials and surface science, atomic and molecular physics, chemistry and structural and molecular biology using SRS includes: the interaction between the proteins actin and gelsolin which has relevance to genetic disease; the crystallinity of polythene; the epitaxial growth of lattice-mismatched semi-conducting material systems; cell uptake of molecules by receptor-mediated endocytosis; the crystal structure of copper-palladium alloys; the kinetics of intercalation and its application to molecular electronics; the crystal structure of the minerals antigorite and chrysotile; the development of experimental facilities to allow surface studies of catalytic processes. Major upgrades and improvements in the SRS are also reported. Highlights of the continuing successful use of parallel supercomputers and distributed computing in the collaborative research undertaken by the Theory, Computational Science and Computing group are presented. These range over applications to pharmaceuticals, plasma and ionization on processes, crystal structures of organic molecules and magnetic storage media. (UK)

  3. Plasma wakefield acceleration at CLARA facility in Daresbury Laboratory

    Science.gov (United States)

    Xia, G.; Nie, Y.; Mete, O.; Hanahoe, K.; Dover, M.; Wigram, M.; Wright, J.; Zhang, J.; Smith, J.; Pacey, T.; Li, Y.; Wei, Y.; Welsch, C.

    2016-09-01

    A plasma accelerator research station (PARS) has been proposed to study the key issues in electron driven plasma wakefield acceleration at CLARA facility in Daresbury Laboratory. In this paper, the quasi-nonlinear regime of beam driven plasma wakefield acceleration is analysed. The wakefield excited by various CLARA beam settings are simulated by using a 2D particle-in-cell (PIC) code. For a single drive beam, an accelerating gradient up to 3 GV/m can be achieved. For a two bunch acceleration scenario, simulation shows that a witness bunch can achieve a significant energy gain in a 10-50 cm long plasma cell.

  4. Simulation studies of plasma lens experiments at Daresbury laboratory

    Science.gov (United States)

    Hanahoe, K.; Mete, O.; Xia, G.; Angal-Kalinin, D.; Jones, J.; Smith, J.

    2016-03-01

    Experiments are planned to study plasma lensing using the VELA and CLARA Front End accelerators at Daresbury Laboratory. This paper presents results of 2-dimensional particle-in-cell simulations of the proposed experiments. The variation in focusing strength and emittance growth with beam and plasma parameters are studied in the overdense (plasma density much greater than bunch density) regime for the VELA beam. The effect of spherical and longitudinal aberrations on the beam emittance was estimated through numerical and theoretical studies. Simulation results show that a focusing strength equivalent to a magnetic field gradient of 10 T m-1 can be achieved using VELA, and a gradient of 247 T m-1 can be achieved using CLARA Front End.

  5. Daresbury 1980

    International Nuclear Information System (INIS)

    This annual report of the Daresbury Laboratory describes work carried out during 1980 on: (1) Synchrotron radiation (synchrotron radiation source, synchrotron radiation experiments, theoretical studies, new projects). (2) Nuclear structure (nuclear structure facility, experimental physics, nuclear physics). (3) Computer services and computational science. (4) Laboratory services. Publications are listed in an appendix. (U.K.)

  6. Daresbury 1975

    International Nuclear Information System (INIS)

    This annual report falls under the following headings: high energy physics (including the NINA programme, CERN programme, technical support and theoretical studies); synchrotron radiation (including studies for the new Synchrotron Radiation Source); nuclear structure (including details of the new Nuclear Structure Facility); computer systems; and appendices covering finance and administration, health and safety, and a list of publications by Daresbury Laboratory staff. (U.K.)

  7. Daresbury 1977

    International Nuclear Information System (INIS)

    The programme of the Daresbury Laboratory is described. Sections on nuclear structure (the building of the Nuclear Structure Facility (NSF), tandem construction, experimental physics, nuclear theory), synchrotron radiation (the synchrotron Radiation Sourse (SRS) and its use in atomic, molecular and solid state physics and X-ray Studies) high energy physics (the NINA and CERN programmes and the closure of the electron synchrotron) and computer systems are included. (U.K.)

  8. Daresbury 1984/5

    International Nuclear Information System (INIS)

    The 1984/85 annual report of the Daresbury Laboratory, United Kingdom, is presented. Attention is centred on the Synchrotron Radiation Source and its scientific programme, and the Nuclear Structure Facility and its experimental work. Theoretical work at Daresbury including computational science is described, as well as computing and electronics. (U.K.)

  9. Daresbury 1981/82

    International Nuclear Information System (INIS)

    This annual report covers the work of the Daresbury Laboratory during the period January 1981 - March 1982 under the headings; nuclear structure (nuclear structure facility, experimental physics), synchrotron radiation (synchrotron radiation source, experimental physics), theory and computational science, computing and electronics, other activities and services. Figures concerning staffing and expenditure are given and laboratory publications covering the period are listed. (U.K.)

  10. Start to End Simulations of the ERL Prototype at Daresbury Laboratory

    CERN Document Server

    Gerth, Christopher; Faatz, Bart; McNeil, Brian W J; Muratori, Bruno; Owen, Hywel; Thompson, Neil

    2005-01-01

    Daresbury Laboratory is currently building an Energy Recovery Linac Prototype (ERLP) that will serve as a research and development facility for the study of beam dynamics and accelerator technology important to the design and construction of the proposed 4th Generation Light Source (4GLS) project. Two major objectives of the ERLP are the demonstration of energy recovery and of energy recovery from a beam disrupted by an FEL interaction as supplied by an infrared oscillator system. In this paper we present start-to-end simulations of the ERLP including such an FEL interaction. The beam dynamics in the high-brightness injector, which consists of a DC photocathode gun and a superconducting booster, have been modelled using the particle tracking code ASTRA. After the booster the particles have been tracked with the code GPT which includes space charge in the injector line at 8.3 MeV. The 3D code GENESIS 1.3 was used to model the FEL interaction with the electron beam at 35 MeV.

  11. Daresbury 1990/91

    International Nuclear Information System (INIS)

    This report highlights some of the diverse range of work engaged in at the Daresbury Laboratory of the United Kingdom Science and Engineering Research Council in 1990/91. It contains brief descriptions of the Laboratory's facilities and research programmes. These fall into three main areas; theory, computational science and computing; lower temperature nuclear physics using the Nuclear Structure Facility; and the development and application of the synchrotron radiation source. Separate appendices to the report cover these areas in greater detail. (UK)

  12. Daresbury 1985/6

    International Nuclear Information System (INIS)

    The paper is the annual report of the Daresbury Laboratory, United Kingdom, 1985/6. The research programme using the Nuclear Structure Facility (NSF) and the Synchrotron Radiation Source (SRS) is described, along with some of the scientific highlights. The performance, operation and other activities associated with the SRS and NSF are summarized. Computational science studies concerned with atoms, molecules, condensed matter, chemical databank service and the FPS-164 computer system, are also outlined. (U.K.)

  13. Daresbury 1989/90

    International Nuclear Information System (INIS)

    This annual report on Daresbury Laboratory for 1989/90 focuses on existing and prospective research efforts. The Synchrotron Radiation Source has been operating effectively and successfully. The Theory and Computational Science group has used many increasingly powerful computing tools. The Nuclear Structure Facility is now fully operational and exciting discoveries, some not predicted by theory, have been observed. Collaboration with the external scientific community has continued successfully as well. (UK)

  14. Daresbury 1987/8

    International Nuclear Information System (INIS)

    1987 was the twenty fifth anniversary of the Daresbury Laboratory and special events were held to celebrate this. Over the twenty five years the projects have changed but the role of the laboratory, which is to provide and operate facilities too large for a single University to operate on its own and to collaborate with the Universities using them, has not changed. The report covers the main facilities at Daresbury. The main events and progress throughout the year are highlighted. For the Nuclear Structure facility highlights included collaboration on the largest array of high resolution germanium gamma-ray detectors ever assembled, work on super deformed nuclei at high angular momentum and the use of the polarised heavy ion source. At the Synchrotron Radiation Source a High Brightness Lattice has been installed and this has resulted in improved imaging and diffraction. Protein molecules, semiconductor materials, very small crystals and muscle structure have been studied using the high brightness lattice facility. A review of the computational science support for projects is included. Facts and figures about Daresbury are presented and a list of publications resulting from work done at the Laboratory during the year is given. (U.K.)

  15. Daresbury 1991/92

    International Nuclear Information System (INIS)

    The report gives an overview of the activities over the year 1991/92. There are more than 4000 registered uses of the facilities at Daresbury so only the highlights can be included. The largest programme is that centred on the Synchrotron Radiation source. During the year this was shut down so that a second superconducting wiggler magnet could be installed. The smallest programme is that associated with Theory, Computational Science and Computing. Collaboration between the Medical and the Science and Engineering Research Councils reflects the interest of both in structural biology. A feasibility study for an Advanced Proton Source has been undertaken as part of the long-term planning for the laboratory. The work on EUROGAM, a Joint UK/France Gamma-Ray Detector is reported. A list of publications of scientists using the facilities at the laboratory is included. Separate appendices are available on the SRS, NSF (Nuclear Structure) and the Theory, Computational Science and Computing facilities. (UK)

  16. Daresbury 1978

    International Nuclear Information System (INIS)

    The report falls under the following headings: introduction; synchrotron radiation (synchrotron radiation source, synchrotron radiation experiments, theoretical studies); nuclear structure (nuclear structure facility, NSF experimental physics, nuclear theory); computational science; high energy physics; computer systems; laboratory services; appendix (publications). (U.K.)

  17. Daresbury 1988/89

    International Nuclear Information System (INIS)

    The main areas of research reported from the Daresbury Laboratory are in synchrotron radiation, nuclear physics and theory and computational science. The Synchrotron Radiation source research programme has employed the experimental techniques of small angle scattering, protein crystallography, surface diffraction, powder diffraction and x-ray absorption spectroscopy. These have been applied to such problems as corrosion in steels, kinetics in cell biology, the structure of viruses (notably the foot-and-mouth virus), sulphur disruption of metal surfaces, metal-semiconductor interfaces, and the electronic and vibrational structure of molecules. Research with the Nuclear Structure Facility has included experiments to study nuclear collective motion, nuclei far from stability and nuclear reaction mechanisms. Much development effort has been directed towards the production of beams of polarized nuclei. Other highlights have been work with the Recoil Separator on exotic nuclei, the Giant Dipole Resonance and isomers. A problem of particular theoretical interest is the effect of breakup on the nucleus-nucleus potential. In computational science, the Laboratory is in the forefront of software development for the collection and theoretical analysis of experimental data and university research is supported through a series of Collaborative Computational Projects. Industrial collaboration in computational science is extending the contribution of the Laboratory to the solution of significant technological problems. (UK)

  18. Around the laboratories: Dubna: Physics results and progress on bubble chamber techniques; Stanford (SLAC): Operation of a very rapid cycling bubble chamber; Daresbury: Photographs of visitors to the Laboratory; Argonne: Charge exchange injection tests into the ZGS in preparation for a proposed Booster

    CERN Multimedia

    1969-01-01

    Around the laboratories: Dubna: Physics results and progress on bubble chamber techniques; Stanford (SLAC): Operation of a very rapid cycling bubble chamber; Daresbury: Photographs of visitors to the Laboratory; Argonne: Charge exchange injection tests into the ZGS in preparation for a proposed Booster

  19. Daresbury 1992/93

    International Nuclear Information System (INIS)

    An overview of the activities at Daresbury over the year 1992/3 is given. The Nuclear Structure Facility (NSF) was closed at the end of March 1993. The EUROGAM gamma-ray spectrometer was brought into operation in October 1992 and the scheduled experiments were completed before the NSF closure. The results are still being analysed by the participating groups. A detailed explanation of EUROGAM and some of the experimental results obtained are given. The Synchrotron Radiation Source has continued to provide powerful light beams for academic and and industrial users to study the physical properties of matter. A new wiggler magnet has improved its operation and research into solid catalysts sleeping sickness, the measurement of spin and orbital angular momentum, surface structure and the photodissociation and photoionization of hydrogen has been carried out. The computational science activities are described. Two new areas of research are medium energy ion scattering and the Research Unit for Surfaces, Transforms and Interfaces. (UK)

  20. Synchrotron radiation: appendix to the Daresbury annual report 1990/91

    International Nuclear Information System (INIS)

    This Appendix to the Annual Report of the Daresbury Laboratory of the United Kingdom Science and Engineering Research Council contains the 1990 Annual Report of the Synchrotron Radiation Facilities Committee, specifications for the beamlines and stations, the index for the synchrotron radiation user reports, the reports themselves and the list of publications detailing work performed on the Synchrotron Radiation Source. By far the largest part of the Appendix is taken up with the user reports for the period 1990 to 1991. They include reports on structural determination of sodium methyl, an investigation of DNA-Binding Proteins, monitoring of vital processes in live cells, the structure of semiconductor interfaces, the structure and properties of glasses and soft x-ray absorption spectroscopy of liquid samples. (author)

  1. Synchrotron radiation. Appendix to the Daresbury annual report 1993/1994

    International Nuclear Information System (INIS)

    This appendix to the main report of the Daresbury Laboratory contains 387 contributions on research carried out using the Synchrotron Radiation Source. The research areas covered include: biological solution scattering; protein crystallography; biological radiation damage; biological spectroscopy; fibre diffraction of biological systems; membranes and liquid systems; machine physics; polymer studies; quantum wells; carbon fibre diffraction; organometallics; phase studies at high pressure; semiconductors; metal oxides; magnetic materials; non-linear optics; alloys; metallic glass; amorphous materials/aqueous solutions; porous silicon and mesoporous materials; silica sols and emulsions; thin films; geology and mineralogy; liquid crystals; catalysis; ceramics and glass; superconductors; detectors for structural biology; metal oxide gas sensors; X-ray scattering techniques; new developments in X-ray techniques; structural studies of powders; single crystal and small molecule crystallography; molecular spectroscopy; lime resolved spectroscopy; surface spectroscopy; topography and diffuse scattering; X-ray microscopy; X-ray studies of surfaces. (UK)

  2. Nuclear physics: appendix to the Daresbury annual report 1990/91

    International Nuclear Information System (INIS)

    This nuclear physics chapter of the Annual Report of the Daresbury Laboratory of the United Kingdom Science and Engineering Research Council describes the work of the Nuclear Structure Facility. In the limited space available it necessarily provides only a broad outline of the facility, its development and a flavour of the research in a selection of a few highlighted topics. This appendix complements the first volume of the Report reproducing users' short camera ready scientific reports. These describe the progress and results of each experimental proposal. Reports are grouped in five sections: research into nuclear structure with contributions ordered in increasing Z number of the nuclei studies; investigations of nuclear reaction mechanisms; nuclear theory; atomic physics; and accelerator operations, developments and instrumentation. The appendix forms a compact record of the work of the Nuclear Structure Facility for the year 1990/91. (author)

  3. Results from the Daresbury Compton backscattering X-ray source

    Science.gov (United States)

    Laundy, D.; Priebe, G.; Jamison, S. P.; Graham, D. M.; Phillips, P. J.; Smith, S. L.; Saveliev, Y.; Vassilev, S.; Seddon, E. A.

    2012-10-01

    The Daresbury Compton Backscattering X-ray Source uses a high power Ti Sapphire laser interacting in head on geometry with electron bunches in the ALICE energy recovery linear accelerator. X-ray photons with peak energy of 21 keV were generated with the accelerator operating at an energy of 29.6 MeV. The spatial profile of the X-rays emitted near the electron beam axis was measured. The characteristics of the X-ray yield measured as a function of relative timing between the laser pulse and the interacting electron bunch was found to be consistent with the modelled intensity behaviour using measured electron and laser beam parameters.

  4. Improved ACE-FTS observations of carbon tetrachloride (CCl4)

    Science.gov (United States)

    Harrison, Jeremy; Chipperfield, Martyn; Boone, Chris; Bernath, Peter

    2016-04-01

    The Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS), on board the SCISAT satellite, has been recording solar occultation spectra through the Earth's atmosphere since 2004 and continues to take measurements with only minor loss in performance. ACE-FTS time series are available for a range of chlorine 'source' gases, including CCl3F (CFC-11), CCl2F2 (CFC-12), CHF2Cl (HCFC-22), CH3Cl and CCl4. Recently there has been much community interest in carbon tetrachloride (CCl4), a substance regulated by the Montreal Protocol because it leads to the catalytic destruction of stratospheric ozone. Estimated sources and sinks of CCl4 remain inconsistent with observations of its abundance. Satellite observations of CCl4 in the stratosphere are particularly useful in validating stratospheric loss (photolysis) rates; in fact the atmospheric loss of CCl4 is essentially all due to photolysis in the stratosphere. However, the latest ACE-FTS v3.5 CCl4 retrieval is biased high by ˜ 20-30%. A new ACE-FTS retrieval scheme utilising new laboratory spectroscopic measurements of CCl4 and improved microwindow selection has recently been developed. This improves upon the v3.5 retrieval and resolves the issue of the high bias; this new scheme will form the basis for the upcoming v4 processing version of ACE-FTS data. This presentation will outline the improvements made in the retrieval, and a subset of data will be compared with modelled CCl4 distributions from SLIMCAT, a state-of-the-art three-dimensional chemical transport model. The use of ACE-FTS data to evaluate the modelled stratospheric loss rate of CCl4 will also be discussed. The evaluated model, which also includes a treatment of surface soil and ocean sinks, will then be used to quantify current uncertainties in the global budget of CCl4.

  5. Age dating ground water by use of chlorofluorocarbons (CCl3F and CCl2F2), and distribution of chlorofluorocarbons in the unsaturated zone, Snake River Plain aquifer, Idaho National Engineering Laboratory, Idaho

    International Nuclear Information System (INIS)

    Detectable concentrations of chlorofluorocarbons (CFC's) were observed in ground water and unsaturated-zone air at the Idaho National Engineering Laboratory (INEL) and vicinity. The recharge ages of waters were determined to be from 4 to more than 50 years on the basis of CFC concentrations and other environmental data; most ground waters have ages of 14 to 30 years. These results indicate that young ground water was added at various locations to the older regional ground water (greater than 50 years) within and outside the INEL boundaries. The wells drilled into the Snake River Plain aquifer at INEL sampled mainly this local recharge. The Big Lost River, Birch Creek, the Little Lost River, and the Mud Lake-Terreton area appear to be major sources of recharge of the Snake River Plain aquifer at INEL. An average recharge temperature of 9.7±1.3 degrees C (degrees Celsius) was calculated from dissolved nitrogen and argon concentrations in the ground waters, a temperature that is similar to the mean annual soil temperature of 9 degrees C measured at INEL. This similarity indicates that the aquifer was recharged at INEL and not at higher elevations that would have cooler soil temperatures than INEL. Soil-gas concentrations at Test Area North (TAN) are explained by diffusion theory

  6. SRP meeting: social and political implications of communicating radiation risk, Daresbury, Warrington, 20 June 2001

    International Nuclear Information System (INIS)

    The SRP held a very interesting meeting in June at the Daresbury Laboratory in Warrington on the social and political implications of communicating radiation risk. In today's risk-aware society, effective communication is just as important as the control measures introduced to prevent or restrict exposure. In relation to radiation protection, risk communicators had a hard job because of: Public dread Likelihood of risk intensification Perceived inequitable distribution of risks. The higher the uncertainty, the more wary people were likely to be. Julie cited the International Nuclear Events Scale (INES) as a possible tool for promoting a consistent message across all publics. This was because it aimed to put events into proper perspective and provide a common understanding amongst the nuclear community, the media and the public. Julie summed up by saying that the risk communication was not just any form of communication and the issue of communicating radiation risks involved special consideration. Further research established that the more information given to the local population, the more likely that they would deny that there was a problem. Denial could moderate beliefs or emotional reactions to a situation. This then affected their dose as they were more likely to adopt risky behaviour by eating contaminated food and entering contaminated areas. Avoiding the need to undertake safe behaviour reduced stress levels. Furthermore, people adopted beliefs to suit their situation. For example, some inhabitants of the affected areas became adapted to the radiation and actually felt worse outside the contaminated area. There was strong pressure for the maintenance of a situation which actually prevented appropriate precautions being taken. Peter concluded that there was often confusion over the details of technical information that sometimes might not help to prevent a course of action being taken. However on a positive note the research did find credence and positive

  7. CCL2 modulates cytokine production in cultured mouse astrocytes

    Directory of Open Access Journals (Sweden)

    Frugier Tony

    2010-10-01

    Full Text Available Abstract Background The chemokine CCL2 (also known as monocyte chemoattractant protein-1, or MCP-1 is upregulated in patients and rodent models of traumatic brain injury (TBI, contributing to post-traumatic neuroinflammation and degeneration by directing the infiltration of blood-derived macrophages into the injured brain. Our laboratory has previously reported that Ccl2-/- mice show reduced macrophage accumulation and tissue damage, corresponding to improved motor recovery, following experimental TBI. Surprisingly, Ccl2-deficient mice also exhibited delayed but exacerbated secretion of key proinflammatory cytokines in the injured cortex. Thus we sought to further characterise CCL2's potential ability to modulate immunoactivation of astrocytes in vitro. Methods Primary astrocytes were isolated from neonatal wild-type and Ccl2-deficient mice. Established astrocyte cultures were stimulated with various concentrations of lipopolysaccharide (LPS and interleukin (IL-1β for up to 24 hours. Separate experiments involved pre-incubation with mouse recombinant (rCCL2 prior to IL-1β stimulation in wild-type cells. Following stimulation, cytokine secretion was measured in culture supernatant by immunoassays, whilst cytokine gene expression was quantified by real-time reverse transcriptase polymerase chain reaction. Results LPS (0.1-100 μg/ml; 8 h induced the significantly greater secretion of five key cytokines and chemokines in Ccl2-/- astrocytes compared to wild-type cells. Consistently, IL-6 mRNA levels were 2-fold higher in Ccl2-deficient cells. IL-1β (10 and 50 ng/ml; 2-24 h also resulted in exacerbated IL-6 production from Ccl2-/- cultures. Despite this, treatment of wild-type cultures with rCCL2 alone (50-500 ng/ml did not induce cytokine/chemokine production by astrocytes. However, pre-incubation of wild-type astrocytes with rCCL2 (250 ng/ml, 12 h prior to stimulation with IL-1β (10 ng/ml, 8 h significantly reduced IL-6 protein and gene

  8. Zinc In CCl4 Toxicity

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To investigate the protective effect of zinc in CCl4-induced hepatotoxicity. Methods Rats were treated with zinc acetate for four days. The zinc doses were 5 mg Zn/kg and 10 mg Zn/kg body weight respectively. Two groups of the zinc acetate-treated rats were later challenged with a single dose of CCl4 (1.5 mL/kg body weight). Results Compared to control animals, the plasma of rats treated with CCl4 showed hyperbilirubinaemia, hypoglycaemia, hypercreatinaemia and hypoproteinaemia. When the animals were however supplemented with zinc in form of zinc acetate before being dosed with CCl4, the 5 mg Zn/kg body weight of zinc acetate reversed the hypoproteinaemia induced by CCl4, whereas the 10mg Zn/kg body weight of zinc acetate reversed the hypoglycaemia, hyperbilimbinaemia and hypercreatinaemia induced by CCl4. Conclusion The 10mug Zn/kg body weight of zinc acetate is more consistent in protecting against CCl4 hepatotoxicity. The possible mechanisms of protection are highlighted.

  9. Expanded beam x-ray optics calibration facility at the Daresbury Synchrotron

    DEFF Research Database (Denmark)

    Christensen, Finn Erland; Hornstrup, Allan; FREDERIKSEN, P;

    1994-01-01

    A facility for the calibration of X-ray Space Instrumentation has been established for the Daresbury Synchrotron. The facility provides a continuously tunable beam with (Delta) (lambda) /(lambda) Daresbury Synchrotron. The facility provides a continuously tunable beam with (Delta) (lambda) /(lambda) range from approximately 5 kev to more than 20 kev. At selected energies...... in the interval from 6 kev to 12 kev, the facility features a 1D sheet of X-rays, approximately 200 mm wide, obtained from an extremely asymmetric reflection in large perfect crystals of Si. The beam is collimated to long) beam expander crystals...

  10. Studies of (p, {gamma}) reactions with the Daresbury Recoil Separator at ORNL'S HRIBF

    Energy Technology Data Exchange (ETDEWEB)

    Fitzgerald, R. [Dept. of Physics and Astronomy, Univ. of North Carolina, Chapel Hill, NC 27599 (United States); Abbotoy, E. [Physics Dept., Tennessee Technological Univ., Cookeville, TN 38505 (United States); Bardayan, D.W. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Blackmon, J.C. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Champagne, A.E. [Dept. of Physics and Astronomy, Univ. of North Carolina, Chapel Hill, NC 27599 (United States); Chen, A.A. [A. W. Wright Nuclear Structure Laboratory, Yale Univ., New Haven, CT 06511 (United States); Greife, U. [Dept. of Physics, Colorado School of Mines, Golden, CO 80401 (United States); Hill, D.W. [Physics Dept., Tennessee Technological Univ., Cookeville, TN 38505 (United States); James, A.N. [Univ. of Liverpool, Liverpool L69 3BX, UK (United Kingdom); Kozub, R.L. [Physics Dept., Tennessee Technological Univ., Cookeville, TN 38505 (United States); Lewis, T.A. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Livesay, R. [Dept. of Physics, Colorado School of Mines, Golden, CO 80401 (United States); Ma, Z. [Univ. of Tennessee, Knoxville, TN 37996 (United States); Mahan, S.L. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); McConnell, J.W. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Milner, W.T. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Moazen, B.H. [Physics Dept., Tennessee Technological Univ., Cookeville, TN 38505 (United States); Parker, P.D. [A. W. Wright Nuclear Structure Laboratory, Yale Univ., New Haven, CT 06511 (United States); Pierce, D.E. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Roettger, M.E. [Physics Dept., Tennessee Technological Univ., Cookeville, TN 38505 (United States)] [and others

    2005-02-07

    The fusion of protons with radioactive nuclei is important in stellar explosions such as novae and X-ray bursts and for the production of neutrinos in the sun. The Daresbury Recoil Separator and a windowless gas target system have been installed at ORNL's Holifield Radioactive Ion Beam Facility (HRIBF) for measurements of proton capture reactions in inverse kinematics with radioactive ion beams. The performance of the system has been characterized with a number of experiments using stable ion beams. We report on results from these commissioning measurements and plans for measurements of the {sup 1}H({sup 17}F,{sup 18}Ne) and {sup 1}H({sup 7}Be,{sup 8}B) reactions.

  11. Induction of the Chemokines CCL3α, CCL3α and CCL5 in Atherosclerotic Patients

    Directory of Open Access Journals (Sweden)

    Alyaa Mousa

    2007-01-01

    Full Text Available Chemokines recruit immune cells to inflammatory sites and promote the process of inflammation. The role of these mediators in the disease process in atherosclerosis is not fully studied. The spontaneous mRNA expression and intracellular protein production of the potential inflammatory chemokines CCL3 and CCL3 (macrophage- inflammatory protein-1and ; CCR3 ligand and CCL5 (regulated upon activation, normal T cell expressed and secreted (RANTES; CCR5 ligand in atherosclerotic patients was examined together with the effects of the chlamydial antigen HSP60 and LPS on the gene expression and protein induction of these mediators. Detection of chemokine mRNA and protein levels was assessed by in situ hybridization and immunohistochemistry respectively. The examined chemokines were detected at significantly high levels on atherosclerotic patients compared to healthy controls at both mRNA and protein levels. Stimulation with HSP60 and LPS from Chlamydia pneumoniae (C. pneumoniae and E. coli showed increased numbers of CCL3, CCL3 and CCL5 mRNA expressing cells in patients compared to health controls. Protein translation of these chemokines was depicted in correspondence to the mRNA gene expression for all examined chemokines spontaneously and after stimulation with chlamydial HSP60 and LPS and E. coli LPS. Thus, the herein data demonstrate the induction of potential inflammatory chemokines in atherosclerotic patients and that bacterial antigens play a role in the immunopathologic events in this disease by generating more inflammatory mediators.

  12. CCL8 BASED IMMUNOLOGICAL MONITORING

    DEFF Research Database (Denmark)

    2008-01-01

    The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of CCL8.The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other...

  13. Recent Developments on ALICE (Accelerators and Lasers In Combined Experiments) at Daresbury Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Saveliev, Y M; Buckley, R K; Buckley, S R; Clarke, J A; Corlett, P A; Dunning, D J; Goulden, A R; Hill, S F; Jackson, F; Jamison, S P; Jones, J K; Jones, L B; Leonard, S; McIntosh, P A; McKenzie, J W; Middleman, K J; Militsyn, B L; Moss, A J; Muratori, B D; Orrett, J F; Pattalwar, S M; Phillips, P J; Scott, D J; Seddon, E A; Shepherd, B.J.A.; Smith, S L; Thompson, N; Wheelhouse, A E; Williams, P H; Harrison, P; Holder, D J; Holder, G M; Schofield, A L; Weightman, P; Williams, R L; Laundry, D; Powers, T; Priebe, G

    2010-05-01

    Progress made in ALICE (Accelerators and Lasers In Combined Experiments) commissioning and a summary of the latest experimental results are presented in this paper. After an extensive work on beam loading effects in SC RF linac (booster) and linac cavities conditioning, ALICE can now operate in full energy recovery mode at the bunch charge of 40pC, the beam energy of 30MeV and train lengths of up to 100us. This improved operation of the machine resulted in generation of coherently enhanced broadband THz radiation with the energy of several tens of uJ per pulse and in successful demonstration of the Compton Backscattering x-ray source experiment. The next steps in the ALICE scientific programme are commissioning of the IR FEL and start of the research on the first non-scaling FFAG accelerator EMMA. Results from both projects will be also reported.

  14. Recent Developments on ALICE (Accelerators and Lasers In Combined Experiments) at Daresbury Laboratory

    International Nuclear Information System (INIS)

    Progress made in ALICE (Accelerators and Lasers In Combined Experiments) commissioning and a summary of the latest experimental results are presented in this paper. After an extensive work on beam loading effects in SC RF linac (booster) and linac cavities conditioning, ALICE can now operate in full energy recovery mode at the bunch charge of 40pC, the beam energy of 30MeV and train lengths of up to 100us. This improved operation of the machine resulted in generation of coherently enhanced broadband THz radiation with the energy of several tens of uJ per pulse and in successful demonstration of the Compton Backscattering x-ray source experiment. The next steps in the ALICE scientific programme are commissioning of the IR FEL and start of the research on the first non-scaling FFAG accelerator EMMA. Results from both projects will be also reported.

  15. Higher Expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 Chemokines in the Skin Associated with Parasite Density in Canine Visceral Leishmaniasis

    Science.gov (United States)

    Menezes-Souza, Daniel; Guerra-Sá, Renata; Carneiro, Cláudia Martins; Vitoriano-Souza, Juliana; Giunchetti, Rodolfo Cordeiro; Teixeira-Carvalho, Andréa; Silveira-Lemos, Denise; Oliveira, Guilherme Corrêa; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

    2012-01-01

    Background The immune response in the skin of dogs infected with Leishmania infantum is poorly understood, and limited studies have described the immunopathological profile with regard to distinct levels of tissue parasitism and the clinical progression of canine visceral leishmaniasis (CVL). Methodology/Principal Findings A detailed analysis of inflammatory cells (neutrophils, eosinophils, mast cells, lymphocytes, and macrophages) as well as the expression of chemokines (CCL2, CCL4, CCL5, CCL13, CCL17, CCL21, CCL24, and CXCL8) was carried out in dermis skin samples from 35 dogs that were naturally infected with L. infantum. The analysis was based on real-time polymerase chain reaction (PCR) in the context of skin parasitism and the clinical status of CVL. We demonstrated increased inflammatory infiltrate composed mainly of mononuclear cells in the skin of animals with severe forms of CVL and high parasite density. Analysis of the inflammatory cell profile of the skin revealed an increase in the number of macrophages and reductions in lymphocytes, eosinophils, and mast cells that correlated with clinical progression of the disease. Additionally, enhanced parasite density was correlated with an increase in macrophages and decreases in eosinophils and mast cells. The chemokine mRNA expression demonstrated that enhanced parasite density was positively correlated with the expression of CCL2, CCL4, CCL5, CCL21, and CXCL8. In contrast, there was a negative correlation between parasite density and CCL24 expression. Conclusions/Significance These findings represent an advance in the knowledge about skin inflammatory infiltrates in CVL and the systemic consequences. Additionally, the findings may contribute to the design of new and more efficient prophylactic tools and immunological therapies against CVL. PMID:22506080

  16. Beneficial impact of CCL2 and CCL12 neutralization on experimental malignant pleural effusion.

    Directory of Open Access Journals (Sweden)

    Antonia Marazioti

    Full Text Available Using genetic interventions, we previously determined that C-C motif chemokine ligand 2 (CCL2 promotes malignant pleural effusion (MPE formation in mice. Here we conducted preclinical studies aimed at assessing the specific therapeutic potential of antibody-mediated CCL2 blockade against MPE. For this, murine MPEs or skin tumors were generated in C57BL/6 mice by intrapleural or subcutaneous delivery of lung (LLC or colon (MC38 adenocarcinoma cells. Human lung adenocarcinoma cells (A549 were used to induce MPEs in severe combined immunodeficient mice. Intraperitoneal antibodies neutralizing mouse CCL2 and/or CCL12, a murine CCL2 ortholog, were administered at 10 or 50 mg/kg every three days. We found that high doses of CCL2/12 neutralizing antibody treatment (50 mg/kg were required to limit MPE formation by LLC cells. CCL2 and CCL12 blockade were equally potent inhibitors of MPE development by LLC cells. Combined CCL2 and CCL12 neutralization was also effective against MC38-induced MPE and prolonged the survival of mice in both syngeneic models. Mouse-specific CCL2-blockade limited A549-caused xenogeneic MPE, indicating that host-derived CCL2 also contributes to MPE precipitation in mice. The impact of CCL2/12 antagonism was associated with inhibition of immune and vascular MPE-related phenomena, such as inflammation, new blood vessel assembly and plasma extravasation into the pleural space. We conclude that CCL2 and CCL12 blockade are effective against experimental MPE induced by murine and human adenocarcinoma in mice. These results suggest that CCL2-targeted therapies may hold promise for future use against human MPE.

  17. Anti-CCL2: building a reservoir or opening the floodgates to metastasis?

    Science.gov (United States)

    Hitchcock, Jessica R; Watson, Christine J

    2015-05-21

    Neutralisation of macrophage chemoattractant C-C chemokine ligand 2 (CCL2) has shown reduced metastasis and enhanced survival in numerous experimental models of tumorigenesis. However, important new findings reported in Nature by Momo Bentires-Alj's laboratory demonstrate that withdrawal of anti-CCL2 treatment accelerates lung metastasis and death in mice. The study highlights the need to consider longer term consequences of therapeutic intervention of metastatic disease, especially with regard to transient interference with the tumour microenvironment.

  18. Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme.

    Science.gov (United States)

    Liang, Wenguang G; Ren, Min; Zhao, Fan; Tang, Wei-Jen

    2015-03-27

    CC chemokine ligands (CCLs) are 8- to 14-kDa signaling proteins involved in diverse immune functions. While CCLs share similar tertiary structures, oligomerization produces highly diverse quaternary structures that protect chemokines from proteolytic degradation and modulate their functions. CCL18 is closely related to CCL3 and CCL4 with respect to both protein sequence and genomic location, yet CCL18 has distinct biochemical and biophysical properties. Here, we report a crystal structure of human CCL18 and its oligomerization states in solution based on crystallographic and small-angle X-ray scattering analyses. Our data show that CCL18 adopts an α-helical conformation at its N-terminus that weakens its dimerization, explaining CCL18's preference for the monomeric state. Multiple contacts between monomers allow CCL18 to reversibly form a unique open-ended oligomer different from those of CCL3, CCL4, and CCL5. Furthermore, these differences hinge on proline 8, which is conserved in CCL3 and CCL4 but is replaced by lysine in human CCL18. Our structural analyses suggest that a mutation of proline 8 to alanine stabilizes a type 1 β-turn at the N-terminus of CCL4 to prevent dimerization but prevents dimers from making key contacts with each other in CCL3. Thus, the P8A mutation induces depolymerization of CCL3 and CCL4 by distinct mechanisms. Finally, we used structural, biochemical, and functional analyses to unravel why insulin-degrading enzyme degrades CCL3 and CCL4 but not CCL18. Our results elucidate the molecular basis for the oligomerization of three closely related CC chemokines and suggest how oligomerization shapes CCL chemokine function.

  19. A detection system for the study of alpha and proton radioactivity on the Daresbury recoil mass separator

    International Nuclear Information System (INIS)

    A detection system has been constructed to measure the alpha and proton decays of short-lived (> μs) nuclear species lying in the proximity of the proton drip line. Proton-rich nuclei produced in fusion-evaporation reactions at angles around 00 are mass separated in flight using the Daresbury Recoil Mass Separator. A two-dimensionally position sensitive silicon surface barrier detector is used to measure evaporation residue implantations and decays. The position information is used to identify the mass of the parent nucleus and to correlate causally related events. The operation and performance of the detection system are described. (orig.)

  20. ADVANCED OXIDATION PROCESSES (AOP'S FOR THE TREATMENT OF CCL CHEMICALS

    Science.gov (United States)

    Research on treatment of Contaminant Candidate List (CCL) chemicals is being conducted. Specific groups of contaminants on the CCL will be evaluated using numerous advanced oxidation processes (AOPs). Initially, these CCL contaminants will be evaluated in groups based on chemical...

  1. X-ray study of a SODART flight telescope using the expanded beam x-ray optics beamline at the Daresbury synchrotron

    DEFF Research Database (Denmark)

    Christensen, Finn Erland; Hornstrup, Allan; Frederiksen, P. K.;

    1995-01-01

    The on- and off-axis imaging properties of the first of two SODART flight telescopes have been studied using the expanded beam x-ray facility at the Daresbury synchrotron. From on- axis measurements the encircled power distribution and the point spread function at three energies 6.627 keV, 8.837 ke...

  2. Immune response CC Chemokines, CCL2 and CCL5 are associated with Pulmonary Sarcoidosis

    LENUS (Irish Health Repository)

    Palchevskiy, Vyacheslav

    2011-04-04

    Abstract Background Pulmonary sarcoidosis involves an intense leukocyte infiltration of the lung with the formation of non-necrotizing granulomas. CC chemokines (chemokine (C-C motif) ligand 2 (CCL2)-CCL5) are chemoattractants of mononuclear cells and act through seven transmembrane G-coupled receptors. Previous studies have demonstrated conflicting results with regard to the associations of these chemokines with sarcoidosis. In an effort to clarify previous discrepancies, we performed the largest observational study to date of CC chemokines in bronchoalveolar lavage fluid (BALF) from patients with pulmonary sarcoidosis. Results BALF chemokine levels from 72 patients affected by pulmonary sarcoidosis were analyzed by enzyme-linked immunosorbent assay (ELISA) and compared to 8 healthy volunteers. BALF CCL3 and CCL4 levels from pulmonary sarcoidosis patients were not increased compared to controls. However, CCL2 and CCL5 levels were elevated, and subgroup analysis showed higher levels of both chemokines in all stages of pulmonary sarcoidosis. CCL2, CCL5, CC chemokine receptor type 1 (CCR1), CCR2 and CCR3 were expressed from mononuclear cells forming the lung granulomas, while CCR5 was only found on mast cells. Conclusions These data suggest that CCL2 and CCL5 are important mediators in recruiting CCR1, CCR2, and CCR3 expressing mononuclear cells as well as CCR5-expressing mast cells during all stages of pulmonary sarcoidosis.

  3. Immune response CC chemokines CCL2 and CCL5 are associated with pulmonary sarcoidosis

    Directory of Open Access Journals (Sweden)

    Palchevskiy Vyacheslav

    2011-04-01

    Full Text Available Abstract Background Pulmonary sarcoidosis involves an intense leukocyte infiltration of the lung with the formation of non-necrotizing granulomas. CC chemokines (chemokine (C-C motif ligand 2 (CCL2-CCL5 are chemoattractants of mononuclear cells and act through seven transmembrane G-coupled receptors. Previous studies have demonstrated conflicting results with regard to the associations of these chemokines with sarcoidosis. In an effort to clarify previous discrepancies, we performed the largest observational study to date of CC chemokines in bronchoalveolar lavage fluid (BALF from patients with pulmonary sarcoidosis. Results BALF chemokine levels from 72 patients affected by pulmonary sarcoidosis were analyzed by enzyme-linked immunosorbent assay (ELISA and compared to 8 healthy volunteers. BALF CCL3 and CCL4 levels from pulmonary sarcoidosis patients were not increased compared to controls. However, CCL2 and CCL5 levels were elevated, and subgroup analysis showed higher levels of both chemokines in all stages of pulmonary sarcoidosis. CCL2, CCL5, CC chemokine receptor type 1 (CCR1, CCR2 and CCR3 were expressed from mononuclear cells forming the lung granulomas, while CCR5 was only found on mast cells. Conclusions These data suggest that CCL2 and CCL5 are important mediators in recruiting CCR1, CCR2, and CCR3 expressing mononuclear cells as well as CCR5-expressing mast cells during all stages of pulmonary sarcoidosis.

  4. Assessing the Atmospheric Impact of CF3CClH2 (HCFC-133a): Laboratory Measurements of OH Kinetics and UV and Infrared Absorption Spectra Combined with Model Calculations

    Science.gov (United States)

    McGillen, M.; Bernard, F.; Fleming, E. L.; Jackman, C. H.; Burkholder, J. B.

    2014-12-01

    CF3CClH2 (HCFC-133a) was recently detected in the atmosphere and its atmospheric mixing ratio has quadrupled over the last 10 years. As expected for this class of compound, HCFC-133a is both an ozone-depleting substance and a greenhouse gas. Precise knowledge of its atmospheric degradation and radiative efficiency is critical to understanding its effect upon the atmosphere. The predominant atmospheric loss process for HCFC-133a is via reaction with the OH radical, where the rate coefficient for this reaction is poorly constrained, especially below room temperature. UV photolysis is a minor loss process, although large discrepancies exist among the reported spectrum measurements. The infrared spectrum of HCFC-133a is presently not available in the literature. The primary focus of this work was to reduce the uncertainties in the atmospheric loss processes of HCFC-133a and its radiative efficiency. Rate coefficient measurements for the OH + HCFC-133a reaction over the temperature range 233-397 K will be reported. In addition, UV absorption spectrum measurements over the wavelength (184.95-240 nm) and temperature (213-323 K) ranges and infrared absorption measurements from 500-4000 cm-1 will be reported. These results are used in 2-D atmospheric model calculations to quantify the atmospheric loss processes, atmospheric lifetime, ozone depletion potential, radiative efficiency, and global warming potential of HCFC-133a. These important metrics will enable informed policy decisions regarding HCFC-133a.

  5. Direct measurements of (p, {gamma}) cross-sections at astrophysical energies using radioactive beams and the Daresbury Recoil Separator

    Energy Technology Data Exchange (ETDEWEB)

    Bardayan, D.W.; Nesaraja, C.D.; Smith, M.S. [Oak Ridge National Laboratory, Physics Division, Oak Ridge, TN (United States); Chipps, K.A.; Greife, U. [Colorado School of Mines, Department of Physics, Golden, CO (United States); Fitzgerald, R.P.; Champagne, A.E. [University of North Carolina, Department of Physics and Astronomy, Chapel Hill, NC (United States); Blackmon, J.C. [Oak Ridge National Laboratory, Physics Division, Oak Ridge, TN (United States); Louisiana State University, Department of Physics and Astronomy, Baton Rouge, LA (United States); Chae, K.Y.; Moazen, B.H.; Pittman, S.T. [University of Tennessee, Department of Physics and Astronomy, Knoxville, TN (United States); Hatarik, R.; Peters, W.A. [Rutgers University, Department of Physics and Astronomy, New Brunswick, NJ (United States); Kozub, R.L.; Shriner, J.F. [Tennessee Technological University, Physics Department, Cookeville, TN (United States); Matei, C. [Oak Ridge Associated Universities, Oak Ridge, TN (United States); Pain, S.D. [Oak Ridge National Laboratory, Physics Division, Oak Ridge, TN (United States); Rutgers University, Department of Physics and Astronomy, New Brunswick, NJ (United States)

    2009-12-15

    There are a number of astrophysical environments in which the path of nucleosynthesis proceeds through proton-rich nuclei. These nuclei have traditionally not been available as beams, and thus proton-capture reactions on these nuclei could only be studied indirectly. At the Holifield Radioactive Ion Beam Facility (HRIBF), some of the first direct measurements of (p,{gamma}) cross-sections on radioactive beams have been made. The Daresbury Recoil Separator (DRS) has been used to separate the recoils of interest from the unreacted primary beam and identify them in an isobutane-filled ionization counter. First data from {sup 17}F (p,{gamma}){sup 18}Ne and {sup 7}Be(p,{gamma}){sup 8}B measurements are presented. (orig.)

  6. Macrophage derived chemokine (CCL22, thymus and activation-regulated chemokine (CCL17, and CCR4 in idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Yamaguchi Kazuhiro

    2009-08-01

    Full Text Available Abstract Background Idiopathic pulmonary fibrosis (IPF is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation of the macrophage-derived chemokine CCL22 and the thymus activation-regulated chemokine CCL17 among chemokines, in a rat model of radiation pneumonitis/pulmonary fibrosis and preliminarily observed an increase in bronchoalveolar (BAL fluid CCL22 levels of IPF patients. Methods We examined the expression of CCR4, a specific receptor for CCL22 and CCL17, in bronchoalveolar lavage (BAL fluid cells, as well as the levels of CCL22 and CCL17, to elucidate their pathophysiological roles in pulmonary fibrosis. We also studied their immunohistochemical localization. Results BAL fluid CCL22 and CCL17 levels were significantly higher in patients with IPF than those with collagen vascular diseases and healthy volunteers, and there was a significant correlation between the levels of CCL22 and CCL17 in patients with IPF. CCL22 levels in the BAL fluid did not correlate with the total cell numbers, alveolar lymphocytes, or macrophages in BAL fluid. However, the CCL22 levels significantly correlated with the numbers of CCR4-expressing alveolar macrophages. By immunohistochemical and immunofluorescence analysis, localization of CCL22 and CCR4 to CD68-positive alveolar macrophages as well as that of CCL17 to hyperplastic epithelial cells were shown. Clinically, CCL22 BAL fluid levels inversely correlated with DLco/VA values in IPF patients. Conclusion We speculated that locally overexpressed CCL22 may induce lung dysfunction through recruitment and activation of CCR4-positive alveolar macrophages.

  7. Many Roles of CCL20: Emphasis on Breast Cancer

    Science.gov (United States)

    Osuala, Kingsley O.; Sloane, Bonnie F.

    2016-01-01

    CCL20 or MIP3α is a small ~8 kDa protein primarily expressed in the liver, colon, prostate, cervix, and skin. The cellular receptor for CCL20 is CCR6. CCl20 unlike many other cytokines only binds CCR6, making the CCL20/CCR6 pathway an attractive drug target. Since the initial discovery of CCL20 in the early 1990's, there has been an increase in the evidence implicating the chemokine and its receptor in a number of diseases, including rheumatoid arthritis and human immunodeficiency virus infection. CCL20 has also been linked to malignancies such as ovarian, colorectal and pancreatic cancers. CCL20 can also attract tumor-promoting immune-suppressive cells to the tumor microenvironment, which may contribute to the immune evasive potential of the tumor and tumor progression.

  8. Systemic levels of CCL2, CCL3, CCL4 and CXCL8 differ according to age, time period and season among children newly diagnosed with type 1 diabetes and their healthy siblings

    DEFF Research Database (Denmark)

    Thorsen, S U; Eising, S; Mortensen, H B;

    2014-01-01

    -based registry of children diagnosed with T1D from 1997 to 2005, we studied five different inflammatory chemokines (CCL2, CCL3, CCL4, CCL5 and CXCL8). Four hundred and eighty-two cases and 479 sibling frequencies matched on age and sample year distribution were included. Patients showed lower levels of CCL4...... compared to siblings, but this result was not significant after correction for multiple testing. CCL2, CCL3, CCL4 and CXCL8 levels were highest in the most recent cohorts (P

  9. Chemokines CXCL10 and CCL2

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Sellebjerg, F; Jensen, C V;

    2001-01-01

    Studies of chemokines in cerebrospinal fluid (CSF) of patients with active multiple sclerosis (MS) have indicated that specific chemokines may have important roles in disease pathogenesis. We previously reported that CSF concentrations of CXCL10 (previously known as IP-10) were elevated in MS...... patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials....... The levels of CXCL10 were higher in the patient group than in controls but two outliers in the control group also had high CSF concentrations of CXCL10. The CSF concentrations of CXCL10 did not change over time or after treatment. The CSF concentration of CXCL10 was positively correlated with the CSF...

  10. CCL7 and CCL21 overexpression in gastric cancer is associated with lymph node metastasis and poor prognosis

    Institute of Scientific and Technical Information of China (English)

    Tsann-Long Hwang; Li-Yu Lee; Chee-Chan Wang; Ying Liang; Shu-Fang Huang; Chi-Ming Wu

    2012-01-01

    AIM:TO investigate how a complex network of CC chemokine ligands (CCLs) and their receptors influence the progression of tumor and metastasis.METHODS:In the present study,we used immunohistochemistry to examine the expression of CCL7,CCL8 and CCL21 in 194 gastric cancer samples and adjacent normal tissues.We analyzed their correlation with tumor metastasis,clinicopathologic parameters and clinical outcome.RESULTS:We found that the higher expression of CCL7 and CCL21 in cancer tissues than in normal tissues was significantly correlated with advanced depth of wall invasion,lymph node metastasis and higher tumor node metastasis stage.Moreover,Kaplan-Meier survival analysis revealed that CCL7 and CCL21 overexpression in cancer tissues was correlated with poor prognosis.CONCLUSION:These results suggest that overexpression of these two CC chemokine ligands is associated with tumor metastasis and serves as a prognostic factor in patients with gastric cancer.

  11. MicroRNA-33 suppresses CCL2 expression in chondrocytes.

    Science.gov (United States)

    Wei, Meng; Xie, Qingyun; Zhu, Jun; Wang, Tao; Zhang, Fan; Cheng, Yue; Guo, Dongyang; Wang, Ying; Mo, Liweng; Wang, Shuai

    2016-06-01

    CCL2-mediated macrophage infiltration in articular tissues plays a pivotal role in the development of the osteoarthritis (OA). miRNAs regulate the onset and progression of diseases via controlling the expression of a series of genes. How the CCL2 gene was regulated by miRNAs was still not fully elucidated. In the present study, we demonstrated that the binding sites of miR-33 in the 3'UTR of CCL2 gene were conserved in human, mouse and rat species. By performing gain- or loss-of-function studies, we verified that miR-33 suppressed CCL2 expression in the mRNA and protein levels. We also found that miR-33 suppressed the CCL2 levels in the supernatant of cultured primary mouse chondrocytes. With reporter gene assay, we demonstrated that miR-33 targeted at AAUGCA in the 3'UTR of CCL2 gene. In transwell migration assays, we demonstrated that the conditional medium (CM) from miR-33 deficient chondrocytes potentiated the monocyte chemotaxis in a CCL2 dependent manner. Finally, we demonstrated that the level of miR-33 was decreased, whereas the CCL2 level was increased in the articular cartilage from the OA patients compared with the control group. In summary, we identified miR-33 as a novel suppressor of CCL2 in chondrocytes. The miR-33/CCL2 axis in chondrocytes regulates monocyte chemotaxis, providing a potential mechanism of macrophage infiltration in OA.

  12. Structural And Functional Characterization of CC Chemokine CCL14

    Energy Technology Data Exchange (ETDEWEB)

    Blain, K.Y.; Kwiatkowski, W.; Zhao, Q.; Fleur, D.La; Naik, C.; Chun, T.-W.; Tsareva, T.; Kanakaraj, P.; Laird, M.W.; Shah, R.; George, L.; Sanyal, I.; Moore, P.A.; Demeler, B.; Choe, S.

    2009-06-02

    CC chemokine ligand 14, CCL14, is a human CC chemokine that is of recent interest because of its natural ability, upon proteolytic processing of the first eight NH{sub 2}-terminal residues, to bind to and signal through the human immunodeficiency virus type-1 (HIV-1) co-receptor, CC chemokine receptor 5 (CCR5). We report X-ray crystallographic structures of both full-length CCL14 and signaling-active, truncated CCL14 [9-74] determined at 2.23 and 1.8 {angstrom}, respectively. Although CCL14 and CCL14 [9-74] differ in their ability to bind CCR5 for biological signaling, we find that the NH{sub 2}-terminal eight amino acids (residues 1 through 8) are completely disordered in CCL14 and both show the identical mode of the dimeric assembly characteristic of the CC type chemokine structures. However, analytical ultracentrifugation studies reveal that the CCL14 is stable as a dimer at a concentration as low as 100 nM, whereas CCL14 [9-74] is fully monomeric at the same concentration. By the same method, the equilibrium between monomers of CCL14 [9-74] and higher order oligomers is estimated to be of EC{sub 1,4} = 4.98 {mu}M for monomer-tetramer conversion. The relative instability of CCL14 [9-74] oligomers as compared to CCL14 is also reflected in the K{sub d}'s that are estimated by the surface plasmon resonance method to be {approx}9.84 and 667 nM for CCL14 and CCL14 [9-74], respectively. This {approx}60-fold difference in stability at a physiologically relevant concentration can potentially account for their different signaling ability. Functional data from the activity assays by intracellular calcium flux and inhibition of CCR5-mediated HIV-1 entry show that only CCL14 [9-74] is fully active at these near-physiological concentrations where CCL14 [9-74] is monomeric and CCL14 is dimeric. These results together suggest that the ability of CCL14 [9-74] to monomerize can play a role for cellular activation.

  13. CCL2 mediates the circadian response to low dose endotoxin.

    Science.gov (United States)

    Duhart, José M; Brocardo, Lucila; Mul Fedele, Malena L; Guglielmotti, Angelo; Golombek, Diego A

    2016-09-01

    The mammalian circadian system is mainly originated in a master oscillator located in the suprachiasmatic nuclei (SCN) in the hypothalamus. Previous reports from our and other groups have shown that the SCN are sensitive to systemic immune activation during the early night, through a mechanism that relies on the action of proinflammatory factors within this structure. Chemokine (C-C motif) ligand 2 (CCL2) is induced in the brain upon peripheral immune activation, and it has been shown to modulate neuronal physiology. In the present work we tested whether CCL2 might be involved in the response of the circadian clock to peripheral endotoxin administration. The CCL2 receptor, C-C chemokine receptor type 2 (CCR2), was detected in the SCN of mice, with higher levels of expression during the early night, when the clock is sensitive to immune activation. Ccl2 was induced in the SCN upon intraperitoneal lipopolysaccharide (LPS) administration. Furthermore, mice receiving an intracerebroventricular (Icv) administration of a CCL2 synthesis inhibitor (Bindarit), showed a reduction LPS-induced circadian phase changes and Icv delivery of CCL2 led to phase delays in the circadian clock. In addition, we tested the possibility that CCL2 might also be involved in the photic regulation of the clock. Icv administration of Bindarit did not modify the effects of light pulses on the circadian clock. In summary, we found that CCL2, acting at the SCN level is important for the circadian effects of immune activation. PMID:27178133

  14. Fine structure of the CCl3 UV absorption spectrum and CCl3 kinetics

    DEFF Research Database (Denmark)

    Ellermann, T.

    1992-01-01

    The UV gas-phase spectrum of CCl3 was recorded in the range 220-300 nm using pulse radiolysis of CHCl3/SF6 or CCl4/Ar gas mixtures. The UV spectrum exhibits a pronounced vibrational fine structure which is assigned to transition into the (C2A1'(3s)) Rydberg state. The vibronic progression has a...

  15. Role of CCL3/MIP-1alpha and CCL5/RANTES during acute Trypanosoma cruzi infection in rats.

    Science.gov (United States)

    Roffê, Ester; Oliveira, Fabiano; Souza, Adriano L S; Pinho, Vanessa; Souza, Danielle G; Souza, Patrícia R S; Russo, Remo C; Santiago, Helton C; Romanha, Alvaro J; Tanowitz, Herbert B; Valenzuela, Jesus G; Teixeira, Mauro M

    2010-08-01

    Chagas' disease is caused by Trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. Chemokines are produced during infection and drive tissue inflammation. In rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. We investigated the role of CCL3 and CCL5 during infection by using DNA vaccination encoding for each chemokine separately or simultaneously. MetRANTES treatment was used to evaluate the role of CCR1 and CCR5, the receptors for CCL3 and CCL5. Vaccination with CCL3 or CCL5 increased heart parasitism and decreased local IFN-gamma production, but did not influence intensity of inflammation. Simultaneous treatment with both plasmids or treatment with MetRANTES enhanced cardiac inflammation, fibrosis and parasitism. In conclusion, chemokines CCL3 and CCL5 are relevant, but not essential, for control of T. cruzi infection in rats. On the other hand, combined blockade of these chemokines or their receptors enhanced tissue inflammation and fibrosis, clearly contrasting with available data in murine models of T. cruzi infection. These data reinforce the important role of chemokines during T. cruzi infection but suggest that caution must be taken when expanding the therapeutic modulation of the chemokine system in mice to the human infection.

  16. Thymic CCL2 influences induction of T-cell tolerance

    DEFF Research Database (Denmark)

    Cédile, O; Løbner, M; Toft-Hansen, H;

    2014-01-01

    Thymic epithelial cells (TEC) and dendritic cells (DC) play a role in T cell development by controlling the selection of the T cell receptor repertoire. DC have been described to take up antigens in the periphery and migrate into the thymus where they mediate tolerance via deletion of autoreactive...... T cells, or by induction of natural regulatory T cells. Migration of DC to thymus is driven by chemokine receptors. CCL2, a major ligand for the chemokine receptor CCR2, is an inflammation-associated chemokine that induces the recruitment of immune cells in tissues. CCL2 and CCR2 are implicated...... in promoting experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. We here show that CCL2 is constitutively expressed by endothelial cells and TEC in the thymus. Transgenic mice overexpressing CCL2 in the thymus showed an increased number of thymic plasmacytoid DC...

  17. CCL3L1-CCR5 genotype improves the assessment of AIDS Risk in HIV-1-infected individuals.

    Directory of Open Access Journals (Sweden)

    Hemant Kulkarni

    Full Text Available BACKGROUND: Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy (HAART during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4+ T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk. METHODS AND FINDINGS: In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV+ subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4+ cell count thresholds used to guide HAART initiation. CONCLUSIONS: The combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By tracking a unique aspect of AIDS risk distinct from that captured by the laboratory parameters

  18. Higher circulating levels of chemokines CXCL10, CCL20 and CCL22 in patients with ischemic heart disease.

    Science.gov (United States)

    Safa, A; Rashidinejad, H R; Khalili, M; Dabiri, S; Nemati, M; Mohammadi, M M; Jafarzadeh, A

    2016-07-01

    Recruitment of leukocytes is one of the earliest events in the pathogenesis of ischemic heart disease (IHD) and chemokines play an important role in the migration of these cells into the inflammation sites. The aim of this study was to evaluate the CXCL10, CCL20 and CCL22 levels and the single nucleotide polymorphisms (SNPs) rs4508917, rs6749704 and rs4359426 in chemokine genes in patients with IHD to clarify any association. A total of 300 patients with IHD as having acute myocardial infarction (AMI; n=100), stable angina (SA; n=100) or unstable angina (UA; n=100) and 100 healthy subjects as a control group were enrolled to study. Serum samples from all participants were tested for the CXCL10, CCL20 and CCL22 levels by using ELISA. The SNPs were determined by polymerase chain reaction-restriction length polymorphism (PCR-RFLP) method. The mean serum concentrations of CXCL10, CCL20 and CCL22 in AMI patients (395.97±21.20Pg/mL, 108.38±10.31Pg/mL and 1852.58±205.77Pg/mL), SA patients (405.48±27.36Pg/mL, 90.20±7.69Pg/mL and 2322.04±231.23Pg/mL) and UA patients (396.69±22.79Pg/mL, 141.87±18.10Pg/mL and 2754.89±211.70Pg/mL) were significantly higher than in the healthy group (179.38±8.85Pg/mL, 51.92±4.62Pg/mL and 451.82±23.76Pg/mL, respectively; PACE) inhibitors and patients without mentioned treatment regarding the levels of chemokines. The frequency of the GG genotype at SNP rs4508917 in CXCL10 gene was higher, whereas the frequency of the AA genotype at SNP rs4359426 in CCL22 gene was lower in total patients with IHD as compared with healthy subjects (P<0.04 and P<0.002, respectively). These results showed that the higher levels of CXCL10, CCL20 and CCL22 were associated with IHD. The serum levels of chemokines may influence by the certain traditional risk factors of IHD and some studied SNPs, but did not influence by treatment and gender of patients. PMID:27152707

  19. Analysis of the heat capacity for pure CH4 and CH4/CCl4 on graphite near the melting point and calculation of the T-X phase diagram for (CH3)CCl3 + CCl4

    Science.gov (United States)

    Yurtseven, Hamit; Yılmaz, Aygül

    2016-06-01

    We study the temperature dependence of the heat capacity Cp for the pure CH4 and the coadsorbed CH4/CCl4 on graphite near the melting point. The heat capacity peaks are analyzed using the experimental data from the literature by means of the power-law formula. The critical exponents for the heat capacity are deduced below and above the melting point for CH4 (Tm = 104.8 K) and CH4/CCl4 (Tm = 99.2 K). Our exponent values are larger as compared with the predicted values of some theoretical models exhibiting second order transition. Our analyses indicate that the pure methane shows a nearly second order (weak discontinuity in the heat capacity peak), whereas the transition in coadsorbed CH4/CCl4 is of first order (apparent discontinuity in Cp). We also study the T – X phase diagram of a two-component system of CH3CCl3+CCl4 using the Landau phenomenological model. Phase lines of the R+L (rhombohedral+liquid) and FCC+L (face-centred cubic + liquid) are calculated using the observed T – X phase diagram of this binary mixture. Our results show that the Landau mean field theory describes the observed behavior of CH3CCl3+CCl4 adequately. From the calculated T – X phase diagram, critical behavior of some thermodynamic quantities can be predicted at various temperatures and concentrations (CCl4) for a binary mixture of CH3CCl3+CCl4.

  20. Carbon Characterization Laboratory Readiness to Receive Irradiated Graphite Samples

    Energy Technology Data Exchange (ETDEWEB)

    Karen A. Moore

    2011-05-01

    The Carbon Characterization Laboratory (CCL) is located in Labs C19 and C20 of the Idaho National Laboratory Research Center. The CCL was established under the Next Generation Nuclear Plant Project to support graphite and ceramic composite research and development activities. The research conducted in this laboratory will support the Advanced Graphite Creep experiments—a major series of material irradiation experiments within the Next Generation Nuclear Plant Graphite program. The CCL is designed to characterize and test low activated irradiated materials such as high purity graphite, carbon-carbon composites, silicon-carbide composite, and ceramic materials. The laboratory is fully capable of characterizing material properties for both irradiated and nonirradiated materials. Major infrastructural modifications were undertaken to support this new radiological facility at Idaho National Laboratory. Facility modifications are complete, equipment has been installed, radiological controls and operating procedures have been established and work management documents have been created to place the CCL in readiness to receive irradiated graphite samples.

  1. Dynamic Heterogeneity In The Monoclinic Phase Of CCl$_4$

    CERN Document Server

    Caballero, Nirvana B; Carignano, Marcelo; Serra, Pablo

    2016-01-01

    Carbon tetrachloride (CCl$_4$) is one of the simplest compounds having a translationally stable monoclinic phase while exhibiting a rich rotational dynamics below 226 K. Recent nuclear quadrupolar resonance (NQR) experiments revealed that the dynamics of CCl$_4$ is similar to that of the other members of the isostructural series CBr$_{n}$Cl$_{4-n}$, suggesting that the universal relaxation features of canonical glasses such as $\\alpha$- and $\\beta$-relaxation are also present in non-glass formers. Using molecular dynamics (MD) simulations we studied the rotational dynamics in the monoclinic phase of CCl$_4$. The molecules undergo $C3$ type jump-like rotations around each one of the four C-Cl bonds. The rotational dynamics is very well described with a master equation using as the only input the rotational rates measured from the simulated trajectories. It is found that the heterogeneous dynamics emerges from faster and slower modes associated with different rotational axes, which have fixed orientations relat...

  2. Photocatalytic decomposition of CCl4 on Zr-MCM-41

    International Nuclear Information System (INIS)

    Photocatalytic decomposition of CCl4 (80 mg L-1 in H2O) effected by Zr-MCM-41 (Zr incorporated in the amorphous wall of MCM-41) has been studied in the present work. Experimentally, photocatalytic decomposition of CCl4 on Zr-MCM-41 was enhanced by about 1.96 times over that on ZrO2. Photocatalytic decomposition of CCl4 may proceed via a two-electron transfer process that yields mainly CHCl3, Cl- and H2. Since little C2Cl2, C2Cl6 or CH2Cl2 was found, it is unlikely that CHCl3 involved in the secondary photocatalytic degradation process. In addition, photocatalytic splitting of H2O on Zr-MCM-41 was also enhanced. The yield of H2 was 6.5 mmol (g ZrO2)-1. About 68% of this hydrogen (6.5 mmol (g ZrO2)-1) was consumed in the photocatalytic decomposition of CCl4

  3. 15 CFR 738.2 - Commerce Control List (CCL) structure.

    Science.gov (United States)

    2010-01-01

    ... Avionics 8—Marine 9—Propulsion Systems, Space Vehicles and Related Equipment (b) Groups. Within each...) Categories. The CCL is divided into 10 categories, numbered as follows: 0—Nuclear Materials, Facilities and... 1: Missile Technology reasons 2: Nuclear Nonproliferation reasons 3: Chemical & Biological...

  4. CCL3L gene copy number and survival in an HIV-1 infected Zimbabwean population

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Thørner, Lise Wegner; Zinyama, Rutendo;

    2012-01-01

    The C-C motif chemokine ligand 3-like (CCL3L) protein is a potent chemoattractant which by binding to C-C chemokine receptor type 5 (CCR5) inhibits human immunodeficiency virus (HIV) entry. Copy number variation (CNV) of the CCL3L has been shown to be associated with HIV susceptibility and progre......The C-C motif chemokine ligand 3-like (CCL3L) protein is a potent chemoattractant which by binding to C-C chemokine receptor type 5 (CCR5) inhibits human immunodeficiency virus (HIV) entry. Copy number variation (CNV) of the CCL3L has been shown to be associated with HIV susceptibility.......9), viral load (P=0.9), or CCL3 protein levels (P=1.0). Survival among the HIV infected individuals did not differ according to CCL3L copy number. In this cohort, CCL3L CNV did not affect HIV status, pathogenesis, or survival....

  5. Electron-impact dissociative ionization of CClF{sub 3} and CCl{sub 3}F

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Roberto [Facultad de Farmacia, Departamento de Quimica Fisica, Universidad del Pais Vasco, Paseo de la Universidad 7. 01006 Vitoria (Spain); Sierra, Borja [Facultad de Ciencia y Tecnologia, Departamento de Quimica Fisica, Universidad del Pais Vasco, Apdo. 644. 48080 Bilbao (Spain); Basterretxea, Francisco J. [Facultad de Ciencia y Tecnologia, Departamento de Quimica Fisica, Universidad del Pais Vasco, Apdo. 644. 48080 Bilbao (Spain); Sanchez Rayo, Maria N. [Facultad de Ciencia y Tecnologia, Departamento de Quimica Fisica, Universidad del Pais Vasco, Apdo. 644. 48080 Bilbao (Spain); Castano, Fernando [Facultad de Ciencia y Tecnologia, Departamento de Quimica Fisica, Universidad del Pais Vasco, Apdo. 644. 48080 Bilbao (Spain)], E-mail: f.castano@ehu.es

    2006-11-08

    A crossed-beam experiment of well characterized kinetic energy (KE) electrons and supersonic halomethanes CCl{sub 3}F and CClF{sub 3} in Ar carrier has been carried out in order to quantify the kinetic energy distributions (KEDs), the appearance energies (AEs) and the channels involved in the production of nascent ions. The ion KEDs were derived from the band profiles of the time-of-flight mass spectrum and the total KEDs computed using conservation laws. Heavier ions are created with KED peaked at thermal energies in contrast with low mass atoms or other fragments, where the distribution is broader and the maximum is at much higher energies. A discussion of the dissociative ionization pathways derived from the appearance energies, total average KEDs, thermodynamic enthalpies and computed electron dissociation energies is reported. The role of the vibrational and rotational energies into the dissociative processes is also discussed.

  6. Elevated expression of the chemokine CCL18 in chronic rhinosinusitis with nasal polyps

    Science.gov (United States)

    Peterson, Sarah; Poposki, Julie A.; Nagarkar, Deepti R.; Chustz, Regina T.; Peters, Anju T.; Suh, Lydia A.; Carter, Roderick; Norton, James; Harris, Kathleen E.; Grammer, Leslie C.; Tan, Bruce K.; Chandra, Rakesh K.; Conley, David B.; Kern, Robert C.; Schleimer, Robert P.; Kato, Atsushi

    2011-01-01

    Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with Th2-dominant inflammation including eosinophilia, in contrast to non-polypoid CRS (CRSsNP). Chemokine CCL18/PARC (pulmonary and activation regulated chemokine) is known to recruit naïve T cells, B cells, and immature dendritic cells, as well as activate fibroblasts. CCL18is thought to be involved in Th2-related inflammatory diseases including asthma and atopic dermatitis. Objectives The objective of this study was to investigate the expression of CCL18 in patients with CRS. Methods Using nasal polyp tissue (NP) and uncinate tissue (UT) from controls and patients with CRS, we examined the expression of CCL18 mRNA by real-time PCR and measured CCL18 protein by ELISA, western blot and immunofluorescence. Results Compared to UT tissue in control subjects, CCL18 mRNA was significantly increased in NP (p<0.001) and UT (p<0.05) from patients with CRSwNP but not in UT from patients with CRSsNP. Similarly, CCL18 protein was elevated in NP and UT from CRSwNP and levels were even higher in Samter’s triad patients. Immunohistochemical analysis revealed CCL18 expression in inflammatory cells and CCL18+ cells were significantly increased in NP. Immunofluorescence data showed co-localization of CCL18 in CD68+/CD163+/macrophage mannose receptor+ M2 macrophages and tryptase+ mast cells in NP. Levels of CCL18 correlated with markers of M2 macrophages but not with tryptase, suggesting that M2 macrophages are a major CCL18-producing cells in NP. Conclusion Overproduction of CCL18 might contribute to the pathogenesis of CRSwNP through its known activities, which include recruitment of lymphocytes and dendritic cells, activation of fibroblasts, and initiation of local inflammation. PMID:21943944

  7. Regulation of CCL5 expression in smooth muscle cells following arterial injury.

    Directory of Open Access Journals (Sweden)

    Huan Liu

    Full Text Available Chemokines play a crucial role in inflammation and in the pathophysiology of atherosclerosis by recruiting inflammatory immune cells to the endothelium. Chemokine CCL5 has been shown to be involved in atherosclerosis progression. However, little is known about how CCL5 is regulated in vascular smooth muscle cells. In this study we report that CCL5 mRNA expression was induced and peaked in aorta at day 7 and then declined after balloon artery injury, whereas IP-10 and MCP-1 mRNA expression were induced and peaked at day 3 and then rapidly declined.The expression of CCL5 receptors (CCR1, 3 & 5 were also rapidly induced and then declined except CCR5 which expression was still relatively high at day 14 after balloon injury. In rat smooth muscle cells (SMCs, similar as in aorta CCL5 mRNA expression was induced and kept increasing after LPS plus IFN-gamma stimulation, whereas IP-10 mRNA expression was rapidly induced and then declined. Our data further indicate that induction of CCL5 expression in SMCs was mediated by IRF-1 via binding to the IRF-1 response element in CCL5 promoter. Moreover, p38 MAPK was involved in suppression of CCL5 and IP-10 expression in SMCs through common upstream molecule MKK3. The downstream molecule MK2 was required for p38-mediated CCL5 but not IP-10 inhibition. Our findings indicate that CCL5 induction in aorta and SMCs is mediated by IRF-1 while activation of p38 MAPK signaling inhibits CCL5 and IP-10 expression. Methods targeting MK2 expression could be used to selectively regulate CCL5 but not IP-10 expression in SMCs.

  8. Laser capture microdissection and cDNA array analysis of endometrium identify CCL16 and CCL21 as epithelial-derived inflammatory mediators associated with endometriosis

    Directory of Open Access Journals (Sweden)

    Jones Rebecca L

    2007-05-01

    Full Text Available Abstract Background Understanding the pathophysiology of chemokine secretion in endometriosis may offer a novel area of therapeutic intervention. This study aimed to identify chemokines differentially expressed in epithelial glands in eutopic endometrium from normal women and those with endometriosis, and to establish the expression profiles of key chemokines in endometriotic lesions. Methods Laser capture microdissection isolated epithelial glands from endometrial eutopic tissue from women with and without endometriosis in the mid-secretory phase of their menstrual cycles. Gene profiling of the excised glands used a human chemokine and receptor cDNA array. Selected chemokines were further examined using real-time PCR and immunohistochemistry. Results 22 chemokine/receptor genes were upregulated and two downregulated in pooled endometrial epithelium of women with endometriosis compared with controls. CCL16 and CCL21 mRNA was confirmed as elevated in some women with endometriosis compared to controls on individual samples. Immunoreactive CCL16 and CCL21 were predominantly confined to glands in eutopic and ectopic endometrium: leukocytes also stained. Immunoreactive CCL16 was overall higher in glands in ectopic vs. eutopic endometrium from the same woman (P Conclusion This study provides novel candidate molecules and suggests a potential local role for CCL16 and CCL21 as mediators contributing to the inflammatory events associated with endometriosis.

  9. Decomposition of CCl4 and CHCl3 on gliding are plasma.

    Science.gov (United States)

    Indarto, Antonius; Choi, Jae-Wook; Lee, Hwaung; Song, Hyung-Keun

    2006-01-01

    Decomposition of chlorinated hydrocarbons, CCl4 and CHCl3, in gliding plasma was examined. The effects of initial concentrations, total gas flow rates, and power consumption have been investigated. The conversion result was relatively high. It reached 80% for CCl4 and 97% for CHCl3. Using atmospheric air as the carrier gas, the plasma reaction occurred at exothermic reaction and the main products were CO2, CO, and Cl2. Transformation into CCl4 was also detected for CHCl3 decomposition reaction. The conversion of CCl4 and CHCl3 were increased with the increasing applied frequency and decreasing total gas flow rate. PMID:20050553

  10. Impact of Tumor-Derived CCL2 on Macrophage Effector Function

    Directory of Open Access Journals (Sweden)

    Brault M. S.

    2005-01-01

    Full Text Available Monocyte chemoattractant protein-1 (MCP-1, CCL2 is produced by many different types of cells. In the current investigation, the effect of tumor-derived CCL2 on macrophages was evaluated to determine the extent to which this chemokine influenced the innate immune response to cancer. To do this, we used the 4T1 murine mammary carcinoma cell line that constitutively expresses CCL2 and generated 4T1 expressing an antisense CCL2 transcript. The antisense-CCL2-expressing 4T1 produced no detectable CCL2. Macrophages from female BALB/c mice were exposed to supernatants from these tumor cells. The results showed that tumor-derived CCL2 was capable of modulating cytokine gene expression but not protein production in resting, activated, and tumor-associated macrophages. In addition, tumor-derived CCL2 did not affect phagocytic activity, nitric oxide production, or cytolytic activity of the macrophages. Overall, these data suggest that tumor-derived CCL2 does not directly influence macrophage-mediated antitumor activity.

  11. CCL5 activation of CCR5 regulates cell metabolism to enhance proliferation of breast cancer cells.

    Science.gov (United States)

    Gao, Darrin; Rahbar, Ramtin; Fish, Eleanor N

    2016-06-01

    In earlier studies, we showed that CCL5 enhances proliferation and survival of MCF-7 breast cancer cells in an mTOR-dependent manner and we provided evidence that, for T cells, CCL5 activation of CCR5 results in increased glycolysis and enhanced ATP production. Increases in metabolic activity of cancer cells, specifically increased glycolytic activity and increased expression of glucose transporters, are associated with tumour progression. In this report, we provide evidence that CCL5 enhances the proliferation of human breast cancer cell lines (MDA-MB-231, MCF-7) and mouse mammary tumour cells (MMTV-PyMT), mediated by CCR5 activation. Concomitant with enhanced proliferation we show that CCL5 increases cell surface expression of the glucose transporter GLUT1, and increases glucose uptake and ATP production by these cells. Blocking CCL5-inducible glucose uptake abrogates the enhanced proliferation induced by CCL5. We provide evidence that increased glucose uptake is associated with enhanced glycolysis, as measured by extracellular acidification. Moreover, CCL5 enhances the invasive capacity of these breast cancer cells. Using metabolomics, we demonstrate that the metabolic signature of CCL5-treated primary mouse mammary tumour cells reflects increased anabolic metabolism. The implications are that CCL5-CCR5 interactions in the tumour microenvironment regulate metabolic events, specifically glycolysis, to promote tumour proliferation and invasion.

  12. CCL7 Is a Protective Factor Secreted by Mechanically Loaded Osteocytes

    OpenAIRE

    Kitase, Y.; Lee, S.; Gluhak-Heinrich, J; Johnson, M.L.; Harris, S.E.; Bonewald, L. F.

    2014-01-01

    In a search for factors up-regulated by mechanical strain in osteocytes, we discovered that chemokine (C-C motif) ligand 7 (CCL7), a chemotactic myokine, was highly expressed in MLO-Y4 osteocyte-like cells. Although MLO-Y4 cells secrete potent chemotactic factors for osteoclast precursors, CCL7 was not responsible for this activity. CCL7 was increased in osteocytes in response to tooth movement in vivo. Since mechanical loading plays a crucial role in maintaining osteocyte viability, CCL7 was...

  13. CCL7 is a protective factor secreted by mechanically loaded osteocytes.

    Science.gov (United States)

    Kitase, Y; Lee, S; Gluhak-Heinrich, J; Johnson, M L; Harris, S E; Bonewald, L F

    2014-11-01

    In a search for factors up-regulated by mechanical strain in osteocytes, we discovered that chemokine (C-C motif) ligand 7 (CCL7), a chemotactic myokine, was highly expressed in MLO-Y4 osteocyte-like cells. Although MLO-Y4 cells secrete potent chemotactic factors for osteoclast precursors, CCL7 was not responsible for this activity. CCL7 was increased in osteocytes in response to tooth movement in vivo. Since mechanical loading plays a crucial role in maintaining osteocyte viability, CCL7 was tested for protective activity and found to be protective against cell death induced by dexamethasone and etoposide. CCL7 specific antibody partially, but in combination with indomethacin, completely abrogated the protective effects of fluid flow shear stress against dexamethasone-induced cell death. CCL7 activated the β-catenin pathway through phosphorylation of glycogen synthase kinase 3 (GSK-3), suggesting that this pathway is responsible for the observed protective effects. A related cytokine, CCL2, also produced by MLO-Y4 cells but not regulated by mechanical loading, proved to be more potent and protected against cell death induced by not only dexamethasone, but also by Tumor Necrosis Factor α (TNFα). Whereas osteocytes may produce CCL2 in constitutively low levels, a major function of mechanically induced CCL7 may be to selectively protect osteocytes in an autocrine manner against glucocorticoid-induced cell death. PMID:25274752

  14. Decomposition of CCl4 and CHCl3 on gliding arc plasma

    Institute of Scientific and Technical Information of China (English)

    Antonius Indarto; CHOI Jae-wook; LEE Hwaung; SONG Hyung-keun

    2006-01-01

    Decomposition of chlorinated hydrocarbons, CCl4 and CHCl3, in gliding plasma was examined. The effects of initial concentrations, total gas flow rates, and power consumption have been investigated. The conversion result was relatively high. It reached 80% for CCl4 and 97% for CHCl3. Using atmospheric air as the carrier gas, the plasma reaction occurred at exothermic reaction and the main products were CO2, CO, and Cl2. Transformation into CCl4 was also detected for CHCl3 decomposition reaction.The conversion of CCl4 and CHCl3 were increased with the increasing applied frequency and decreasing total gas flow rate.

  15. CONSTRUCTION OF EUKARYOTIC EXPRESSION VECTOR FOR HUMAN CCL21 AND CHARACTERIZATION OF ITS CHEMOTACTIC ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    HOU Li; LIU Qi; JIAO Yu-lian; ZHANG Jie; WANG Lai-cheng; MA Chun-yan; CUI Bin; ZHANG Xue; ZHAO Yue-ran

    2006-01-01

    Objective: To obtain recombinant human CCL21 with biological activity from eukaryotic expression system for further use in cancer gene therapy. Methods: A fragment of human CCL21 gene was obtained from pSK-hCCL21 plasmid digested by Xho I and BamH I, inserted into the responding sites of eukaryotic expression vector pVAX1, and then transfected into COS-7 cells by electroporation method. The expression of hCCL21 protein was detected by western blotting analysis. The in vitro chemotaxis assay was used to test the chemotactic function of the expression product to lymphocytes. Results: Human CCL21 protein was expressed by transfected COS-7 cells with recombinant plasmid containing hCCL21 gene, and was verified by western blotting. The in vitro chemotaxis assay demonstrated that human CCL21 protein had a potent chemotactic function to lymphocytes. Conclusion: Human CCL21 was successfully and transiently expressed in eukaryotic cells, which lays some foundation for the study of CCL21 gene therapy in murine tumor models.

  16. Role of CCL17 and CCL22 expression in dendritic cells in maternal-fetal immune tolerance%母胎界面树突状细胞CCL17和CCL22表达在母胎免疫耐受中的作用

    Institute of Scientific and Technical Information of China (English)

    刘玉昆; 刘梅兰; 王蕴慧; 陈慧; 孟丽丽; 张建平

    2012-01-01

    AIM; To determine the expression of CCL17 and CCL22 in dendrilic cells (DC) from human de-cidua and endomelria. METHODS; The decidua were collecled from normal pregnanl women undergoing induced abortion and recurrent spontaneous abortion ( RSA) women undergoing early abortion. The endomelria were cllecled from non - pregnanl women undergoing abdominal hyslereclomy. The mononuclear cells in the decidua and endomelria were isolated. DC were induced by GM - CSF and IL - 4, cullured in vitro and idenlified. The expression of CCL17 and CCL22 in DC al mR-NA and prolein levels was analyzed by real - lime PCR and ELISA. RESULTS; The mRNA levels of CCL17 and CCL22 in decidual DC in normal pregnancy group were 3.04 ±0.40 and 1.83 ±0.24, respectively, significantly higher than those in endomelrial DC in non - pregnancy group (0. 85 ±0. 24 and 0. 31 ±0. 08 , respectively, P <0. 01) and ihose in decidual DC in RSA group (1.65 ±0. 14 and 0.96 ±0. 09,respectively,P <0. 01) . Decidual DC continually and slrongly secreted CCL17 and CCL22. The levels of CCL17 and CCL22 in normal pregnancy group were significantly higher than those in non - pregnancy group and RSA group at the same culture time point ( P < 0. 01). CONCLUSION; The expression of CCL17 and CCL22 in decidual DC in pregnant woman increases. This may attract more CD4 + CD25 + regulatory T cells to decidua and play an important role in the establishment of maternal - fetal immune tolerance.%目的:检测非孕期子宫内膜和正常妊娠早期及复发性自然流产患者蜕膜中树突状细胞(DC)CCL17和CCL22的表达差异,探讨母胎界面DC在CD4+CD25+调节性T细胞(Treg)的募集及母胎免疫耐受微环境形成中的作用.方法:正常早孕组人工流产时、复发性流产组清宫时取其蜕膜,正常未孕组行子宫切除时取其内膜组织.分离蜕膜或子宫内膜单个核细胞,体外诱导培养DC,用real-time PCR法分析3组DC CCL17和CCL22 mRNA的表达水平,ELISA法检测3组DC培养上清液中CCL

  17. Mutations in BALB mitochondrial DNA induce CCL20 up-regulation promoting tumorigenic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Sligh, James [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Janda, Jaroslav [University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Jandova, Jana, E-mail: jjandova@email.arizona.edu [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States)

    2014-11-15

    Highlights: • Alterations in mitochondrial DNA are commonly found in various human cancers. • Mutations in BALB mitochondrial DNA induce up-regulation of chemokine CCL20. • Increased growth and motility of mtBALB cells is associated with CCL20 levels. • mtDNA changes in BALB induce in vivo tumor growth through CCL20 up-regulation. • Mutations in mitochondrial DNA play important roles in keratinocyte neoplasia. - Abstract: mtDNA mutations are common in human cancers and are thought to contribute to the process of neoplasia. We examined the role of mtDNA mutations in skin cancer by generating fibroblast cybrids harboring a mutation in the gene encoding the mitochondrial tRNA for arginine. This somatic mutation (9821insA) was previously reported in UV-induced hyperkeratotic skin tumors in hairless mice and confers specific tumorigenic phenotypes to mutant cybrids. Microarray analysis revealed and RT-PCR along with Western blot analysis confirmed the up-regulation of CCL20 and its receptor CCR6 in mtBALB haplotype containing the mt-Tr 9821insA allele compared to wild type mtB6 haplotype. Based on reported role of CCL20 in cancer progression we examined whether the hyper-proliferation and enhanced motility of mtBALB haplotype would be associated with CCL20 levels. Treatment of both genotypes with recombinant CCL20 (rmCCL20) resulted in enhanced growth and motility of mtB6 cybrids. Furthermore, the acquired somatic alteration increased the in vivo tumor growth of mtBALB cybrids through the up-regulation of CCL20 since neutralizing antibody significantly decreased in vivo tumor growth of these cells; and tumors from anti-CCL20 treated mice injected with mtBALB cybrids showed significantly decreased CCL20 levels. When rmCCL20 or mtBALB cybrids were used as chemotactic stimuli, mtB6 cybrids showed increased motility while anti-CCL20 antibody decreased the migration and in vivo tumor growth of mtBALB cybrids. Moreover, the inhibitors of MAPK signaling and NF

  18. CCL20/CCR6 Signaling Regulates Bone Mass Accrual in Mice.

    Science.gov (United States)

    Doucet, Michele; Jayaraman, Swaathi; Swenson, Emily; Tusing, Brittany; Weber, Kristy L; Kominsky, Scott L

    2016-07-01

    CCL20 is a member of the macrophage inflammatory protein family and is reported to signal monogamously through the receptor CCR6. Although studies have identified the genomic locations of both Ccl20 and Ccr6 as regions important for bone quality, the role of CCL20/CCR6 signaling in regulating bone mass is unknown. By micro-computed tomography (μCT) and histomorphometric analysis, we show that global loss of Ccr6 in mice significantly decreases trabecular bone mass coincident with reduced osteoblast numbers. Notably, CCL20 and CCR6 were co-expressed in osteoblast progenitors and levels increased during osteoblast differentiation, indicating the potential of CCL20/CCR6 signaling to influence osteoblasts through both autocrine and paracrine actions. With respect to autocrine effects, CCR6 was found to act as a functional G protein-coupled receptor in osteoblasts and although its loss did not appear to affect the number or proliferation rate of osteoblast progenitors, differentiation was significantly inhibited as evidenced by delays in osteoblast marker gene expression, alkaline phosphatase activity, and mineralization. In addition, CCL20 promoted osteoblast survival concordant with activation of the PI3K-AKT pathway. Beyond these potential autocrine effects, osteoblast-derived CCL20 stimulated the recruitment of macrophages and T cells, known facilitators of osteoblast differentiation and survival. Finally, we generated mice harboring a global deletion of Ccl20 and found that Ccl20(-/-) mice exhibit a reduction in bone mass similar to that observed in Ccr6(-/-) mice, confirming that this phenomenon is regulated by CCL20 rather than alternate CCR6 ligands. Collectively, these data indicate that CCL20/CCR6 signaling may play an important role in regulating bone mass accrual, potentially by modulating osteoblast maturation, survival, and the recruitment of osteoblast-supporting cells. © 2016 American Society for Bone and Mineral Research. PMID:26890063

  19. Corticosterone regulates expression of CCL2 in the intact and chemically injured hippocampus.

    Science.gov (United States)

    Little, Alvin R; Sriram, Krishnan; O'Callaghan, James P

    2006-05-15

    Expression of the chemokine (C-C motif) ligand 2 (CCL2), also known as, monocyte chemoattractant protein (MCP)-1, increases in response to disease-, trauma-, or toxicant-induced damage to the central nervous system (CNS). In the periphery, endogenous and exogenous glucocorticoids are known to suppress CCL2 expression associated with inflammatory conditions. However, such actions of glucocorticoids on CCL2 expression in the CNS remain unknown. Here, we explored the effects of the glucocorticoid, corticosterone (CORT), on the expression of CCL2 and its receptors, CCR2 and CCR5, in the hippocampal formation using intact, adrenalectomized (ADX) and trimethyltin (TMT)-treated rats. An immunosuppressive regimen of CORT did not alter the mRNA expression of CCL2 or its receptors in the hippocampus. ADX, however, markedly increased the expression of CCL2 and CCR2 mRNAs in the hippocampus, while CORT replacement reversed the effects of ADX on CCL2 gene expression. Hippocampal damage resulting from systemic administration of the organometallic neurotoxicant, TMT, was associated with microglial activation, as evidenced by enhanced expression of microglial markers integrin alphaM (CD11b) and F4/80, as well as, microglia-associated factors, CCL2 and IL-1alpha. An immunosuppressive dose of CORT, suppressed TMT-induced expression of CCL2. Given the association of CCL2 with microglial activation, it appears that CORT may play a role in regulating microglial activation. However, CORT treatment did not alter TMT-mediated neuronal damage and astrogliosis. Such observations suggest that injury-related expression of microglia-associated chemokines and cytokines may subserve a role unrelated to neuronal damage. In summary, our data indicate that in the CNS, CCL2 gene expression is under negative regulation by glucocorticoids.

  20. Upregulated baseline plasma CCL19 and CCR7 cell-surface expression on monocytes in early rheumatoid arthritis normalized during treatment and CCL19 correlated with radiographic progression

    DEFF Research Database (Denmark)

    Ellingsen, T; Hansen, I; Thorsen, J;

    2014-01-01

    OBJECTIVES: The aim of this study was to measure, in early rheumatoid arthritis (RA) patients, the concentration of CC-chemokine ligand 19 (CCL19) in plasma and the cell-surface expression of CC-chemokine receptor 7 (CCR7) on circulating monocytes and CD4+ T lymphocytes and to analyse correlations...... with disease activity and 5-year radiographic progression. METHOD: In disease-modifying anti-rheumatic drug (DMARD)-naïve RA patients (disease duration < 6 months), we measured plasma CCL19 by enzyme-linked immunosorbent assay (ELISA) (n = 160) and CCR7 cell-surface expression on monocytes and CD4+ T......-naïve RA patients, CCL19 plasma level and CCR7 surface expression on monocytes were upregulated and normalized after 1 year of treatment. Increased baseline plasma CCL19 level, anti-CCP antibody status, and TSS > 0 at baseline correlated independently with 5-year radiographic progression....

  1. Antioksidan Ekstrak Air Biji Kopi Robusta Lampung dalam Menghambat Degenerasi Sel Hati Tikus Model Hepatitis yang Diinduksi CCL4

    Directory of Open Access Journals (Sweden)

    Asep Sukohar

    2012-09-01

    Full Text Available Liver plays an important role in maintaining homeostasis and is critical for physiological functions of other organs. Morphological changes of the liver will have an impact on changes in liver function and may appear as clinical manifestations. Hepatitis is a serious disorder that causes inflammation of the liver cells and is caused by viruses, chemicals and toxins. Reactions that occur in the form of oxidative stress, free radicals dominant condition of antioxidants. Traditionally coffee is used as an everyday beverage and known as antioxidants because it contains flavonoids (chlorogenic acid. This study aim was to determine the hepatoprotective/antioxidant effect of coffee growing in Pesawaran Lampung, on the description of hepatocyte cell damage in Wistar rats hepatitis model induced with carbon tetrachloride (CCl4. Laboratory experimental research has been conducted in Pharmacology >Department, Faculty Medicine Padjadjaran University Bandung and pathology examinations was performed at the Hospital Abdoel Moeloek Lampung in December 2008–July 2009, using 15 male Wistar rats divided in three groups, the negative control group, positive control as a model of hepatitis, and hepatitis model that received the water extract of robusta coffee beans 25 mg/kgBW/days for 7 days and then received CCl4 induction. The results were analyzed by analysis of variance and independent t test. Administration of water extract of robusta coffee beans can prevented damage to the liver cell degeneration picture from 58.4±7.09 to 34.4±5.85, these results differed significantly (p≤0.05 compared with positive and negative control. In conclusion, water extract of robusta coffee beans has the potential to prevent interference with the effects of liver function as antioxidants in the ra model of hepatitis which has been inducted with CCL4.

  2. In vivo metabolism of CCl4 by rats pretreated with chlordecone, mirex, or phenobarbital

    International Nuclear Information System (INIS)

    The propensity of chlordecone (CD) to potentiate hepatotoxic and lethal effects of CCl4 is well established. Mirex (M), a close structural analogue of CD, or phenobarbital (PB), powerful inducers of hepatic microsomal drug metabolizing enzymes, are much weaker potentiators of CCl4 toxicity. The purpose of this study was to test the possibility that CD potentiates the toxicity of CCl4 by increasing the metabolism of CCl4 to a greater degree than either PB or M. We compared the in vivo metabolism of CCl4 in rats pretreated with CD, M, or PB, by measuring the hepatic content of 14CCl4, the expiration of 14CCl4, expiration of 14CCl4-derived 14CO2, and lipid peroxidation. Male Sprague-Dawley rats (250-270 g) were pretreated with a single oral dose of CD (10 mg/kg), M (10 mg/kg), or corn oil vehicle (1 ml/kg). PB pretreatment consisted of an ip injection of sodium PB (80 mg/kg) in saline (0.9%) for 2 successive days. Twenty-four hours later, 14CCl4 (0.1 ml/kg; sp act: 0.04 mCi/mmol) was administered ip in corn oil and the radioactivity present in the expired air was collected for 6 hr. Excretion of the parent compound as represented by the 14C label in the toluene trap was unchanged by any of the pretreatments. Expiration of 14CO2 measured during the 6 hr after CCl4 administration was increased in animals pretreated with PB or CD. In vivo lipid peroxidation measured as diene conjugation in lipids extracted from the livers was increased to a similar extent in animals pretreated with PB and CD, whereas the serum transaminases (ALT, AST) were significantly elevated only in animals pretreated with CD.M did not affect 14CO2 production and was without a significant effect on the lipid peroxidation

  3. CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.

    Directory of Open Access Journals (Sweden)

    Zahra Hasan

    Full Text Available BACKGROUND: Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNgamma, TNFalpha and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity. METHODOLOGY: We investigated live M. tuberculosis- and M. bovis BCG-induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB and healthy endemic controls (ECs, n = 36. TB patients comprised pulmonary (PTB, n = 34 and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16 or severe disseminated ETB (D-ETB, n = 16. Secretion of CCL2, IFNgamma, IL10 and CCL3, and mRNA expression of CCL2, TNFalpha, CCL3 and CXCL8 were determined. RESULTS: M. tuberculosis- and BCG-induced CCL2 secretion was significantly increased in both PTB and D-ETB (p<0.05, p<0.01 as compared with L-ETB patients. CCL2 secretion in response to M. tuberculosis was significantly greater than to BCG in the PTB and D-ETB groups. M. tuberculosis-induced CCL2 mRNA transcription was greater in PTB than L-ETB (p = 0.023, while CCL2 was reduced in L-ETB as compared with D-ETB (p = 0.005 patients. M. tuberculosis-induced IFNgamma was greater in L-ETB than PTB (p = 0.04, while BCG-induced IFNgamma was greater in L-ETB as compared with D-ETB patients (p = 0.036. TNFalpha mRNA expression was raised in PTB as compared with L-ETB group in response to M. tuberculosis (p = 0.02 and BCG (p = 0.03. Mycobacterium-induced CCL3 and CXCL8 was comparable between TB groups. CONCLUSIONS: The increased CCL2 and TNFalpha in PTB patients may support effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is associated with severity of TB, possibly due to increased systemic inflammation found in severe disseminated TB or due to increased monocyte infiltration to lung parenchyma in pulmonary disease.

  4. In vivo metabolism of CCl4 by gerbils pretreated with chlordecone, phenobarbital, or mirex

    International Nuclear Information System (INIS)

    Gerbils are known to be much more sensitive to CCl4 lethality than rats as indicated by 48 hours LD50 (0.08 vs 2.8 ml/kg). On the other hand, gerbils are refractory to chlordecone (CD) potentiation of CCl4 toxicity. To investigate the possible mechanism underlying gerbil's high sensitivity to CCl4 lethality, the authors studied in vivo metabolism of CCl4 in gerbils pretreated with dietary CD (10 ppm), phenobarbital (PB, 225 ppm) or mirex (M, 10 ppm). The hepatic content of CCl4, the expiration of 14CCl4 and 14CCl4-derived Co2, and lipid peroxidation were measured and the results were compared with our previous data for rats. After 15-day dietary pretreatment, male gerbils (60-80 g) received 14CCl4 (80 ml/kg; sp act: 0.04 mCi/mmol) ip in corn oil and the expired air was collected for 6 hours. More than 80% of the dose administered was expired as parent compound in 6 hours regardless of pretreatments. Expiration of 14CCl4 derived 14CO2 in control gerbils was 3.5-fold more than in control rats and was increased significantly in pretreated gerbils (M>PB>CD). PB and M pretreatments resulted in significant increase of 14C label bound to non-lipid fraction of hepatic content as compared with CD or control gerbils. The radiolabel present in hepatic content of control gerbils was 5-fold higher than that of control rats. In vivo liquid peroxidation measured as diene conjugation in lipid extracts from the livers was lower in gerbils than in rats, and there were no significant differences among control and pretreated gerbils. These data indicate that the more extensive metabolism of CCl4 in gerbils may partially explain their high sensitivity to CCl4 toxicity. However, the significantly enhanced metabolism of CCl4 found in CD, PB, or M pretreated gerbils did not lead to amplification of CCl4 hepatotoxic and lethal effects

  5. Ccl2, Cx3cr1 and Ccl2/Cx3cr1 chemokine deficiencies are not sufficient to cause age-related retinal degeneration.

    Science.gov (United States)

    Luhmann, Ulrich F O; Carvalho, Livia S; Robbie, Scott J; Cowing, Jill A; Duran, Yanai; Munro, Peter M G; Bainbridge, James W B; Ali, Robin R

    2013-02-01

    Monocytes, macrophages, dendritic cells and microglia play critical roles in the local immune response to acute and chronic tissue injury and have been implicated in the pathogenesis of age-related macular degeneration. Defects in Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling cause enhanced accumulation of bloated subretinal microglia/macrophages in senescent mice and this phenomenon is reported to result in the acceleration of age-related retinal degeneration. The purpose of this study was to determine whether defects in CCL2-CCR2 and CX3CL1-CX3CR1 signalling pathways, alone or in combination, cause age-dependent retinal degeneration. We tested whether three chemokine knockout mouse lines, Ccl2(-/-), Cx3cr1(-/-) and Ccl2(-/-)/Cx3cr1(-/-), in comparison to age-matched C57Bl/6 control mice show differences in subretinal macrophage accumulation and loss of adjacent photoreceptor cells at 12-14 months of age. All mouse lines are derived from common parental strains and do not carry the homozygous rd8 mutation in the Crb1 gene that has been a major confounding factor in previous reports. We quantified subretinal macrophages by counting autofluorescent lesions in fundus images obtained by scanning laser ophthalmoscopy (AF-SLO) and by immunohistochemistry for Iba1 positive cells. The accumulation of subretinal macrophages was enhanced in Ccl2(-/-), but not in Cx3cr1(-/-) or Ccl2(-/-)/Cx3cr1(-/-) mice. We identified no evidence of retinal degeneration in any of these mouse lines by TUNEL staining or semithin histology. In conclusion, CCL2-CCR2 and/or CX3CL1-CX3CR1 signalling defects may differentially affect the trafficking of microglia and macrophages in the retina during ageing, but do not appear to cause age-related retinal degeneration in mice.

  6. UV and infrared absorption spectra, atmospheric lifetimes, and ozone depletion and global warming potentials for CCl2FCCl2F (CFC-112), CCl3CClF2 (CFC-112a), CCl3CF3 (CFC-113a), and CCl2FCF3 (CFC-114a)

    Science.gov (United States)

    Davis, Maxine E.; Bernard, François; McGillen, Max R.; Fleming, Eric L.; Burkholder, James B.

    2016-07-01

    The potential impact of CCl2FCF3 (CFC-114a) and the recently observed CCl2FCCl2F (CFC-112), CCl3CClF2 (CFC-112a), and CCl3CF3 (CFC-113a) chlorofluorocarbons (CFCs) on stratospheric ozone and climate is presently not well characterized. In this study, the UV absorption spectra of these CFCs were measured between 192.5 and 235 nm over the temperature range 207-323 K. Precise parameterizations of the UV absorption spectra are presented. A 2-D atmospheric model was used to evaluate the CFC atmospheric loss processes, lifetimes, ozone depletion potentials (ODPs), and the associated uncertainty ranges in these metrics due to the kinetic and photochemical uncertainty. The CFCs are primarily removed in the stratosphere by short-wavelength UV photolysis with calculated global annually averaged steady-state lifetimes (years) of 63.6 (61.9-64.7), 51.5 (50.0-52.6), 55.4 (54.3-56.3), and 105.3 (102.9-107.4) for CFC-112, CFC-112a, CFC-113a, and CFC-114a, respectively. The range of lifetimes given in parentheses is due to the 2σ uncertainty in the UV absorption spectra and O(1D) rate coefficients included in the model calculations. The 2-D model was also used to calculate the CFC ozone depletion potentials (ODPs) with values of 0.98, 0.86, 0.73, and 0.72 obtained for CFC-112, CFC-112a, CFC-113a, and CFC-114a, respectively. Using the infrared absorption spectra and lifetimes determined in this work, the CFC global warming potentials (GWPs) were estimated to be 4260 (CFC-112), 3330 (CFC-112a), 3650 (CFC-113a), and 6510 (CFC-114a) for the 100-year time horizon.

  7. CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid-Derived Suppressor Cell Population and Function

    Directory of Open Access Journals (Sweden)

    Eunyoung Chun

    2015-07-01

    Full Text Available Our study reveals a non-canonical role for CCL2 in modulating non-macrophage, myeloid-derived suppressor cells (MDSCs and shaping a tumor-permissive microenvironment during colon cancer development. We found that intratumoral CCL2 levels increased in patients with colitis-associated colorectal cancer (CRC, adenocarcinomas, and adenomas. Deletion of CCL2 blocked progression from dysplasia to adenocarcinoma and reduced the number of colonic MDSCs in a spontaneous mouse model of colitis-associated CRC. In a transplantable mouse model of adenocarcinoma and an APC-driven adenoma model, CCL2 fostered MDSC accumulation in evolving colonic tumors and enhanced polymorphonuclear (PMN-MDSC immunosuppressive features. Mechanistically, CCL2 regulated T cell suppression of PMN-MDSCs in a STAT3-mediated manner. Furthermore, CCL2 neutralization decreased tumor numbers and MDSC accumulation and function. Collectively, our experiments support that perturbing CCL2 and targeting MDSCs may afford therapeutic opportunities for colon cancer interception and prevention.

  8. CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.

    Directory of Open Access Journals (Sweden)

    Béatrice Cambien

    Full Text Available Increased CCL5 levels are markers of an unfavourable outcome in patients with melanoma, breast, cervical, prostate, gastric or pancreatic cancer. Here, we have assessed the role played by CCL5/CCR5 interactions in the development of colon cancer. To do so, we have examined a number of human colorectal carcinoma clinical specimens and found CCL5 and its receptors over-expressed within primary as well as liver and pulmonary metastases of patients compared to healthy tissues. In vitro, CCL5 increased the growth and migratory responses of colon cancer cells from both human and mouse origins. In addition, systemic treatment of mice with CCL5-directed antibodies reduced the extent of development of subcutaneous colon tumors, of liver metastases and of peritoneal carcinosis. Consistently, we found increased numbers of CD45-immunoreactive cells within the stroma of the remaining lesions as well as at the interface with the healthy tissue. In contrast, selective targeting of CCR5 through administration of TAK-779, a CCR5 antagonist, only partially compromised colon cancer progression. Furthermore, CCL5 neutralization rendered the tumors more sensitive to a PDGFRβ-directed strategy in mice, this combination regimen offering the greatest protection against liver metastases and suppressing macroscopic peritoneal carcinosis. Collectively, our data demonstrate the involvement of CCL5 in the pathogenesis of colorectal carcinoma and point to its potential value as a therapeutic target.

  9. Lygodium flexuosum extract down regulates the expression of proinflammatory cytokines in CCl4 -induced hepatotoxicity

    Institute of Scientific and Technical Information of China (English)

    Pallara Janardhanan Wills; Velikkakathu Vasumathi Asha

    2012-01-01

    Objective:To examine the downregulation of proinflammatory cytokines in a time dependant manner on carbon tetrachloride induced toxicity in experimental animals.Methods:CCl4(150 μL/100 g) was dissolved in corn oil(1:1 v/v%) and administered orally.GroupI was treated as normal control and received corn oil on8th day.GroupII was toxic control and was given a single dose ofCCl4 on8th days.GroupIII wastreated withLygodium flexuosum(L. flexuosum)n-hexane extract(200 mg/kg) for8 days and on8th day a single dose ofCCl4 was received.GroupIV(negative control) receivedL. flexuosumn-hexane extract(200 mg/kg) alone for8 days.Results:Treatment withn-hexane extract prior to the administration ofCCl4 significantly prevented an increase in serumAST,ALT,LDH activity and lipid peroxidation and prevented the depletion of glutathione (GSH).Rats treated withL. flexuosum had reduced mRNA levels ofTGF-β1,TNF-α andIL-1βgenes in liver ofCCl4 intoxicated rats when compared toCCl4 control as evidenced byRT-PCR. Conclusions:The data suggest that L. flexuosum, a widely available fern, significantly reduces CCl4 induced acute hepatotoxicity by down-regulating the expression of pro-inflammatory cytokines in rats.

  10. Variations in CCL3L gene cluster sequence and non-specific gene copy numbers

    Directory of Open Access Journals (Sweden)

    Edberg Jeffrey C

    2010-03-01

    Full Text Available Abstract Background Copy number variations (CNVs of the gene CC chemokine ligand 3-like1 (CCL3L1 have been implicated in HIV-1 susceptibility, but the association has been inconsistent. CCL3L1 shares homology with a cluster of genes localized to chromosome 17q12, namely CCL3, CCL3L2, and, CCL3L3. These genes are involved in host defense and inflammatory processes. Several CNV assays have been developed for the CCL3L1 gene. Findings Through pairwise and multiple alignments of these genes, we have shown that the homology between these genes ranges from 50% to 99% in complete gene sequences and from 70-100% in the exonic regions, with CCL3L1 and CCL3L3 being identical. By use of MEGA 4 and BioEdit, we aligned sense primers, anti-sense primers, and probes used in several previously described assays against pre-multiple alignments of all four chemokine genes. Each set of probes and primers aligned and matched with overlapping sequences in at least two of the four genes, indicating that previously utilized RT-PCR based CNV assays are not specific for only CCL3L1. The four available assays measured median copies of 2 and 3-4 in European and African American, respectively. The concordance between the assays ranged from 0.44-0.83 suggesting individual discordant calls and inconsistencies with the assays from the expected gene coverage from the known sequence. Conclusions This indicates that some of the inconsistencies in the association studies could be due to assays that provide heterogenous results. Sequence information to determine CNV of the three genes separately would allow to test whether their association with the pathogenesis of a human disease or phenotype is affected by an individual gene or by a combination of these genes.

  11. CCL21/IL21-armed oncolytic adenovirus enhances antitumor activity against TERT-positive tumor cells.

    Science.gov (United States)

    Li, Yang; Li, Yi-Fei; Si, Chong-Zhan; Zhu, Yu-Hui; Jin, Yan; Zhu, Tong-Tong; Liu, Ming-Yuan; Liu, Guang-Yao

    2016-07-15

    Multigene-armed oncolytic adenoviruses are capable of efficiently generating a productive antitumor immune response. The chemokine (C-C motif) ligand 21 (CCL21) binds to CCR7 on naïve T cells and dendritic cells (DCs) to promote their chemoattraction to the tumor and resultant antitumor activity. Interleukin 21 (IL21) promotes survival of naïve T cells while maintaining their CCR7 surface expression, which increases their capacity to transmigrate in response to CCL21 chemoattraction. IL21 is also involved in NK cell differentiation and B cell activation and proliferation. The generation of effective antitumor immune responses is a complex process dependent upon coordinated interactions of various subsets of effector cells. Using the AdEasy system, we aimed to construct an oncolytic adenovirus co-expressing CCL21 and IL21 that could selectively replicate in TERTp-positive tumor cells (Ad-CCL21-IL21 virus). The E1A promoter of these oncolytic adenoviruses was replaced by telomerase reverse transcriptase promoter (TERTp). Ad-CCL21-IL21 was constructed from three plasmids, pGTE-IL21, pShuttle-CMV-CCL21 and AdEasy-1 and was homologously recombined and propagated in the Escherichia coli strain BJ5183 and the packaging cell line HEK-293, respectively. Our results showed that our targeted and armed oncolytic adenoviruses Ad-CCL21-IL21 can induce apoptosis in TERTp-positive tumor cells to give rise to viral propagation, in a dose-dependent manner. Importantly, we confirm that these modified oncolytic adenoviruses do not replicate efficiently in normal cells even under high viral loads. Additionally, we investigate the role of Ad-CCL21-IL21 in inducing antitumor activity and tumor specific cytotoxicity of CTLs in vitro. This study suggests that Ad-CCL21-IL21 is a promising targeted tumor-specific oncolytic adenovirus. PMID:27157859

  12. Negative ion formation and motion in a mixture of CCl4 and Ar

    International Nuclear Information System (INIS)

    This paper deals with the measurement of the mobility of negative ions in the mixtures of CCl4 with Ar with the CCl4 ratio up to 33.3%. The pulsed Townsend technique was employed to produce an integrated ionic avalanche over a range of the density-reduced electric field E/N for which ionization is either negligible or absent, and attachment processes are dominant, leading to the formation of mostly CCl4-. The E/N range of measurement was 1-50 Td (1 Td=10-17 V cm2). Our measurements strongly suggest that attachment is the dominant process and only negative ions are formed

  13. Zinc finger protein TTP interacts with CCL3 mRNA and regulates tissue inflammation*

    OpenAIRE

    Kang, Ju-Gyeong; Amar, Marcelo J.; Remaley, Alan T.; Kwon, Jaeyul; Blackshear, Perry J.; Wang, Ping-yuan; Hwang, Paul M.

    2011-01-01

    Zinc finger protein tristetraprolin (TTP) modulates macrophage inflammatory activity by destabilizing cytokine mRNAs. Here, through a screen of TTP-bound mRNAs in activated human macrophages, we have identified CC chemokine ligand 3 (CCL3) mRNA as the most abundantly bound TTP target mRNA and have characterized this interaction via conserved AU-rich elements. Compared to the wild-type cells, TTP−/− macrophages produced higher levels of LPS-induced CCL3. In addition, the plasma level of CCL3 i...

  14. Classification for Chinese Libraries (CCL : Histories, Accomplishments, Problems and Its Comparisons

    Directory of Open Access Journals (Sweden)

    Wenxian Zhang

    2003-09-01

    Full Text Available China has a long history in library classifications, although modern classifications did not emerge until one hundred years ago when the Western classifications were introduced into the country. The Classification for Chinese Libraries (CCL was developed after years of collective work. The purposes of this article are to review the ancient history and modern efforts in developing Chinese library classifications, examine the organizations, accomplishments and problems of the CCL especially in the areas of philosophy and social sciences, and compare the CCL with the Library of Congress Classification (LCC in terms of their structures.

  15. The porcine skin associated T-cell homing chemokine CCL27: molecular cloning and mRNA expression in piglets infected experimentally with Staphylococcus hyicus

    DEFF Research Database (Denmark)

    Johnsen, C. K.; Jensen, Annette Nygaard; Ahrens, P.;

    2003-01-01

    . In this paper, we report the cloning of porcine CCL27 cDNA and investigation of CCL27 mRNA expression in Staphylococcus hyicus infected piglets. At the protein level, 77 and 74% homology was found to human and mouse CCL27 sequences, respectively. The results of the expression analyses show that CCL27 m...

  16. CCL2 Mediates Neuron-Macrophage Interactions to Drive Proregenerative Macrophage Activation Following Preconditioning Injury.

    Science.gov (United States)

    Kwon, Min Jung; Shin, Hae Young; Cui, Yuexian; Kim, Hyosil; Thi, Anh Hong Le; Choi, Jun Young; Kim, Eun Young; Hwang, Dong Hoon; Kim, Byung Gon

    2015-12-01

    CNS neurons in adult mammals do not spontaneously regenerate axons after spinal cord injury. Preconditioning peripheral nerve injury allows the dorsal root ganglia (DRG) sensory axons to regenerate beyond the injury site by promoting expression of regeneration-associated genes. We have previously shown that peripheral nerve injury increases the number of macrophages in the DRGs and that the activated macrophages are critical to the enhancement of intrinsic regeneration capacity. The present study identifies a novel chemokine signal mediated by CCL2 that links regenerating neurons with proregenerative macrophage activation. Neutralization of CCL2 abolished the neurite outgrowth activity of conditioned medium obtained from neuron-macrophage cocultures treated with cAMP. The neuron-macrophage interactions that produced outgrowth-promoting conditioned medium required CCL2 in neurons and CCR2/CCR4 in macrophages. The conditioning effects were abolished in CCL2-deficient mice at 3 and 7 d after sciatic nerve injury, but CCL2 was dispensable for the initial growth response and upregulation of GAP-43 at the 1 d time point. Intraganglionic injection of CCL2 mimicked conditioning injury by mobilizing M2-like macrophages. Finally, overexpression of CCL2 in DRGs promoted sensory axon regeneration in a rat spinal cord injury model without harmful side effects. Our data suggest that CCL2-mediated neuron-macrophage interaction plays a critical role for amplification and maintenance of enhanced regenerative capacity by preconditioning peripheral nerve injury. Manipulation of chemokine signaling mediating neuron-macrophage interactions may represent a novel therapeutic approach to promote axon regeneration after CNS injury.

  17. A comprehensive estimate for loss of atmospheric carbon tetrachloride (CCl4) to the ocean

    Science.gov (United States)

    Butler, James H.; Yvon-Lewis, Shari A.; Lobert, Jurgen M.; King, Daniel B.; Montzka, Stephen A.; Bullister, John L.; Koropalov, Valentin; Elkins, James W.; Hall, Bradley D.; Hu, Lei; Liu, Yina

    2016-09-01

    Extensive undersaturations of carbon tetrachloride (CCl4) in Pacific, Atlantic, and Southern Ocean surface waters indicate that atmospheric CCl4 is consumed in large amounts by the ocean. Observations made on 16 research cruises between 1987 and 2010, ranging in latitude from 60° N to 77° S, show that negative saturations extend over most of the surface ocean. Corrected for physical effects associated with radiative heat flux, mixing, and air injection, these anomalies were commonly on the order of -5 to -10 %, with no clear relationship to temperature, productivity, or other gross surface water characteristics other than being more negative in association with upwelling. The atmospheric flux required to sustain these undersaturations is 12.4 (9.4-15.4) Gg yr-1, a loss rate implying a partial atmospheric lifetime with respect to the oceanic loss of 183 (147-241) yr and that ˜ 18 (14-22) % of atmospheric CCl4 is lost to the ocean. Although CCl4 hydrolyzes in seawater, published hydrolysis rates for this gas are too slow to support such large undersaturations, given our current understanding of air-sea gas exchange rates. The even larger undersaturations in intermediate depth waters associated with reduced oxygen levels, observed in this study and by other investigators, strongly suggest that CCl4 is ubiquitously consumed at mid-depth, presumably by microbiota. Although this subsurface sink creates a gradient that drives a downward flux of CCl4, the gradient alone is not sufficient to explain the observed surface undersaturations. Since known chemical losses are likewise insufficient to sustain the observed undersaturations, this suggests a possible biological sink for CCl4 in surface or near-surface waters of the ocean. The total atmospheric lifetime for CCl4, based on these results and the most recent studies of soil uptake and loss in the stratosphere is now 32 (26-43) yr.

  18. Vibrational spectroscopy of SnBr4 and CCl4 using Lie algebraic approach

    Indian Academy of Sciences (India)

    Joydeep Choudhury; Srinivasa Rao Karmuri; Nirmal Kumar Sarkar; Ramendu Bhattacharjee

    2008-09-01

    The stretching and bending vibrational energies of SnBr4 and CCl4 are calculated in the one-dimensional framework. The dynamical symmetry group of tetrahedral molecule was taken into consideration to construct the model Hamiltonian in this frame-work. Casimir and Majorana invariant operators were also determined accordingly. Using the model Hamiltonian so constructed, we reported the vibrational energy levels of SnBr4 and CCl4 molecules accurately.

  19. Up-regulation of the chemokine CCL21 in the skin of subjects exposed to irritants

    OpenAIRE

    Kuznitzky Raquel; Ruiz Lascano Alejandro; Ortiz Susana; Eberhard Yanina; Serra Horacio

    2004-01-01

    Abstract Background Expression of murine CCL21 by dermal lymphatic endothelial cells (LEC) has been demonstrated to be one of the most important steps in Langerhans cell emigration from skin. Previously, our group and others have found that this chemokine is up-regulated in different human inflammatory skin diseases mediated by diverse specific immune responses. This study was carried out to investigate the involvement of CCL21 in human skin after challenge with irritant agents responsible fo...

  20. Isorhamnetin-3-O-galactoside Protects against CCl4-Induced Hepatic Injury in Mice

    OpenAIRE

    Kim, Dong-Wook; Cho, Hong-Ik; Kim, Kang-Min; Kim, So-Jin; Choi, Jae Sue; Kim, Yeong Shik; Lee, Sun-Mee

    2012-01-01

    This study was performed to examine the hepatoprotective effect of isorhamnetin-3-O-galactoside, a flavonoid glycoside isolated from Artemisia capillaris Thunberg (Compositae), against carbon tetrachloride (CCl4)-induced hepatic injury. Mice were treated intraperitoneally with vehicle or isorhamnetin-3-O-galactoside (50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20 μl/kg) injection. Serum aminotransferase activities and hepatic level of malondialdehyde were significantly higher af...

  1. Up-regulation of the chemokine CCL21 in the skin of subjects exposed to irritants

    Directory of Open Access Journals (Sweden)

    Kuznitzky Raquel

    2004-04-01

    Full Text Available Abstract Background Expression of murine CCL21 by dermal lymphatic endothelial cells (LEC has been demonstrated to be one of the most important steps in Langerhans cell emigration from skin. Previously, our group and others have found that this chemokine is up-regulated in different human inflammatory skin diseases mediated by diverse specific immune responses. This study was carried out to investigate the involvement of CCL21 in human skin after challenge with irritant agents responsible for inducing Irritant Contact Dermatitis (ICD. Results Eleven normal individuals were challenged with different chemical or physical irritants. Two patients with Allergic Contact Dermatitis (ACD were also challenged with the relevant antigen in order to have a positive control for CCL21 expression. Macroscopic as well as microscopic responses were evaluated. We observed typical ICD responses with mostly mononuclear cells in perivascular areas, but a predominance of polymorphonuclear cells away from the inflamed blood vessels and in the epidermis at 24 hours. Immunohistochemical studies showed up-regulation of CCL21 by lymphatic endothelial cells in all the biopsies taken from ICD and ACD lesions compared to normal skin. Kinetic study at 10, 48, 96 and 168 hours after contact with a classical irritant (sodium lauryl sulphate showed that the expression of CCL21 was increased in lymphatic vessels at 10 hours, peaked at 48 hours, and then gradually declined. There was a strong correlation between CCL21 expression and the macroscopic response (r = 0.69; p = 0.0008, but not between CCL21 and the number of infiltrating cells in the lesions. Conclusions These results provide new evidence for the role of CCL21 in inflammatory processes. Since the up-regulation of this chemokine was observed in ICD and ACD, it is tempting to speculate that this mechanism operates independently of the type of dermal insult, facilitating the emigration of CCR7+ cells.

  2. CCL2-ethanol interactions and hippocampal synaptic protein expression in a transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Donna eGruol

    2014-04-01

    Full Text Available Chronic exposure to ethanol produces a number of detrimental effects on behavior. Neuroadaptive changes in brain structure or function underlie these behavioral changes and may be transient or persistent in nature. Central to the functional changes are alterations in the biology of neuronal and glial cells of the brain. Recent data show that ethanol induces glial cells of the brain to produce elevated levels of neuroimmune factors including CCL2, a key innate immune chemokine. Depending on the conditions of ethanol exposure, the upregulated levels of CCL2 can be transient or persistent and outlast the period of ethanol exposure. Importantly, results indicate that the upregulated levels of CCL2 may lead to CCL2-ethanol interactions that mediate or regulate the effects of ethanol on the brain. Glial cells are in close association with neurons and regulate many neuronal functions. Therefore, effects of ethanol on glial cells may underlie some of the effects of ethanol on neurons. To investigate this possibility, we are studying the effects of chronic ethanol on hippocampal synaptic function in a transgenic mouse model that expresses elevated levels of CCL2 in the brain through enhanced glial expression, a situation know to occur in alcoholics. Both CCL2 and ethanol have been reported to alter synaptic function in the hippocampus. In the current study, we determined if interactions are evident between CCL2 and ethanol at level of hippocampal synaptic proteins. Two ethanol exposure paradigms were used; the first involved ethanol exposure by drinking and the second involved ethanol exposure in a paradigm that combines drinking plus ethanol vapor. The first paradigm does not produce dependence on ethanol, whereas the second paradigm is commonly used to produce ethanol dependence. Results show modest effects of both ethanol exposure paradigms on the level of synaptic proteins in the hippocampus of CCL2 transgenic mice compared with their non

  3. Neuronal-derived Ccl7 drives neuropathic pain by promoting astrocyte proliferation.

    Science.gov (United States)

    Ke, Bin Chang; Huang, Xia Xiao; Li, Yang; Li, Li Ya; Xu, Qin Xue; Gao, Yan; Liu, Yingju; Luo, Jie

    2016-08-01

    Recent studies suggest that peripheral nerve injury converts resting spinal cord astroglial cells into an activated state, which is required for the development and maintenance of neuropathic pain. However, the underlying mechanisms of how resting astrocytes are activated after nerve injury remain largely unknown. Astroglial cell proliferation and activation could be affected by endogenous factors including chemokines, growth factors, and neurotropic factor. Chemokine (C-C motif) ligand 7 (Ccl7) is essential in facilitating the development of neuropathic pain; however, the mechanism is unknown. In the present study, we found that Ccl7 promoted astrocyte proliferation and thus contributed toward neuropathic pain. Spinal nerve ligation increased the expression in the spinal cord of neuronal Ccl7. Behavioral analyses showed that knockdown of Ccl7 alleviated spinal nerve ligation-induced neuropathic pain. Further in-vitro study showed that neuronal-derived Ccl7 was sufficient for the proliferation and activation of astroglial cells. We found a novel mechanism of Ccl7 stimulating the proliferation and activation of spinal cord astrocytes that contributes toward neuropathic pain. PMID:27295026

  4. Phase Transition in CCl4 under Pressure: a Raman Spectroscopic Study

    Institute of Scientific and Technical Information of China (English)

    LIU Tie-Cheng; ZHOU Mi; GAO Shu-Qin; LI Zuo-Wei; LI Zhan-Long; ZHANG Peng; LI Liang; LV Tian-Quan; XU Da-Peng

    2009-01-01

    High-pressure Raman studies at room temperature are performed on CCla up to 13 GPa. The Raman bands of the internal modes (v2, v4 and v1) show entirely positive pressure dependence. The slopes dw/dP of the internal modes exhibit two sudden changes at 0.73 GPa and 7.13 GPa, respectively. A new lower frequency mode (225cm-1) appears at 3.03 GPa, and the splitting of v2, v3 and v4 occurs at about 7.13 GPa. Moreover, Raman spectra of Fermi resonance show that the relative position of the v1 + v4 combination and the v3 fundamental firstly interchanges corresponding to that at ambient pressure, then the v1 + va combination disappears in the gradual process of compression. It is indicated that the pressure-induced phase transition from CCl4 II to CCl4 III occurs at 0.73 GPa, and CCl4 III undergoes a transition to CCl4 IV below 3.03 GPa. Further CCl4 IV transforms in a new high-pressure phase at about 7.13 GPa, and the symmetry of the new high-pressure phase is lower than that of CCl4 IV. All the transitions are reversible during decompression.

  5. Therapeutic efficacy and immunological response of CCL5 antagonists in models of contact skin reaction.

    Directory of Open Access Journals (Sweden)

    Miriam Canavese

    Full Text Available Skin-infiltrating T-cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis, psoriasis and allergic contact dermatitis. These T-cells are attracted by several chemotactic factors including the chemokine CCL5/RANTES, a CC chemokine inducing both the migration and activation of specific leukocyte subsets. CCL5 has been found to be associated with various cell-mediated hypersensitive disorders such as psoriasis, atopic dermatitis and irritant contact dermatitis. We have used two antagonists, the first, Met-CCL5, a dual CCR1/CCR5 antagonist and the second, a variant in which GAG binding is abrogated, (44AANA(47-CCL5, which acts as a dominant negative inhibitor of CCL5. The antagonists were tested in two models of contact skin reaction. The first, irritant contact dermatitis (ICD is a pathological non-specific inflammatory skin condition arising from the release of pro-inflammatory cytokines by keratinocytes in response to haptens, usually chemicals. The second, contact hypersensitivity (CHS is a T-cell dependent model, mimicking in part the T-cell-mediated skin diseases such as psoriasis. In both models, the CCL5 antagonists showed therapeutic efficacy by reducing swelling by 50% as well as the reduction of soluble mediators in homogenates derived from challenged ears. These results demonstrate that blocking the receptor or the ligand are both effective strategies to inhibit skin inflammation.

  6. Platelet-Derived CCL5 Regulates CXC Chemokine Formation and Neutrophil Recruitment in Acute Experimental Colitis.

    Science.gov (United States)

    Yu, Changhui; Zhang, Songen; Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Thorlacius, Henrik

    2016-02-01

    Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis.

  7. Molecular Cloning and Sequence Analysis of CCL28 Gene in Oryctolagus cuniculus%兔CCL28基因的克隆与序列分析

    Institute of Scientific and Technical Information of China (English)

    贾海丽; 王艳玲; 韩立强; 王月影; 朱河水; 李平; 刘涛; 杨国宇

    2009-01-01

    克隆并分析兔CCL28基因.基于电子延伸序列,设计1对克隆引物,兔盲肠黏膜组织提取总RNA,进行RT-PCR,将PCR产物与pMD19-T载体连接后转化E.coli JM109感受态细胞、检测阳性克隆、测序并进行序列分析.克隆的兔CCL28 基因片段长为133 bp,编码由44个氨基酸残基组成的CCL28前体蛋白,克隆的兔CCL28基因与绵羊、野猪的同源性分别为76.7%、77.4%,推导的氨基酸序列与绵羊、野猪的同源性分别为56.8%、56.8%,结构特征与绵羊、野猪的相一致.并注册GenBank (Accession.EU727201).

  8. CCL2/MCP-I genotype-phenotype relationship in latent tuberculosis infection.

    Science.gov (United States)

    Hussain, Rabia; Ansari, Ambreen; Talat, Najeeha; Hasan, Zahra; Dawood, Ghaffar

    2011-01-01

    Among the known biomarkers, chemokines, secreted by activated macrophages and T cells, attract groups of immune cells to the site of infection and may determine the clinical outcome. Association studies of CCL-2/MCP-1 -2518 A/G functional SNP linked to high and low phenotypes with tuberculosis disease susceptibility have shown conflicting results in tuberculosis. Some of these differences could be due the variability of latent infection and recent exposure in the control groups. We have therefore carried out a detailed analysis of CCL-2 genotype SNP -2518 (A/G transition) with plasma CCL-2 levels and related these levels to tuberculin skin test positivity in asymptomatic community controls with no known exposure to tuberculosis and in recently exposed household contacts of pulmonary tuberculosis patients. TST positivity was linked to higher concentrations of plasma CCL2 (Mann Whitney U test; p = 0.004) and was more marked when the G allele was present in TST+ asymptomatic controls (A/G; p = 0.01). Recent exposure also had a significant effect on CCL-2 levels and was linked to the G allele (p = 0.007). Therefore association studies for susceptibility or protection from disease should take into consideration the PPD status as well as recent exposure of the controls group used for comparison. Our results also suggest a role for CCL-2 in maintaining the integrity of granuloma in asymptomatic individuals with latent infection in high TB burden settings. Therefore additional studies into the role of CCL-2 in disease reactivation and progression are warranted. PMID:21991356

  9. CCL2/MCP-I genotype-phenotype relationship in latent tuberculosis infection.

    Directory of Open Access Journals (Sweden)

    Rabia Hussain

    Full Text Available Among the known biomarkers, chemokines, secreted by activated macrophages and T cells, attract groups of immune cells to the site of infection and may determine the clinical outcome. Association studies of CCL-2/MCP-1 -2518 A/G functional SNP linked to high and low phenotypes with tuberculosis disease susceptibility have shown conflicting results in tuberculosis. Some of these differences could be due the variability of latent infection and recent exposure in the control groups. We have therefore carried out a detailed analysis of CCL-2 genotype SNP -2518 (A/G transition with plasma CCL-2 levels and related these levels to tuberculin skin test positivity in asymptomatic community controls with no known exposure to tuberculosis and in recently exposed household contacts of pulmonary tuberculosis patients. TST positivity was linked to higher concentrations of plasma CCL2 (Mann Whitney U test; p = 0.004 and was more marked when the G allele was present in TST+ asymptomatic controls (A/G; p = 0.01. Recent exposure also had a significant effect on CCL-2 levels and was linked to the G allele (p = 0.007. Therefore association studies for susceptibility or protection from disease should take into consideration the PPD status as well as recent exposure of the controls group used for comparison. Our results also suggest a role for CCL-2 in maintaining the integrity of granuloma in asymptomatic individuals with latent infection in high TB burden settings. Therefore additional studies into the role of CCL-2 in disease reactivation and progression are warranted.

  10. Experimental study on CCl4/CH)4/O2/N2 oxidation

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Oxidation within the system CCl4/CH4/O2/N2 is studied at atmospheric pressure in a tubular flow reactor to investigate the influence of reaction temperature and chlorine content on chlorinated waste combustion and find incineration process optimization methods for pollution control.The reaction temperature varies from 700℃ to 1000℃ and the CCl4/CH4(or Cl/H) mole ratio of the inlet mixture varies from 0.21 to 0.84.Products profiles are measured with FT-IR.It is shown that at the same initial CCl4 concentration and reaction temperature adding CH4 favors CCl4 destruction and CO2 formation.But the destruction and removal efficiency(DRE) of CH4 decreases with lower Cl/H and higher concentrations of toxic products of incomplete combustion such as COCl2 and CH3Cl are formed at the same time.The chlorine in the system favors CH4 decomposition,but it also inhibits further oxidation of CO.Higher temperature assists in both CCl4 destruction and CH4 conversion,and the concentration of toxic combustion intermediates is reduced.Increasing the temperature is the most effective way to enhance CCl4 oxidation.The CO2 concentration increases with temperature.A CO concentration peak is observed around 800℃:with a certain Cl/H,the CO concentration first increases with temperature and then declines.The effect of increasing CH4 concentration on CCl4 destruction becomes mild above 900℃.Rather,it enhances the interaction between chlorine and carbonaceous radicals,which leads to higher concentration of toxic products.

  11. Expression and histopathological correlation of CCR9 and CCL25 in ovarian cancer.

    Science.gov (United States)

    Singh, Rajesh; Stockard, Cecil R; Grizzle, William E; Lillard, James W; Singh, Shailesh

    2011-08-01

    Ovarian carcinoma is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells. The interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for ovarian cancer cells. We have previously shown that ovarian cancer cells express CCR9 and play an important role in cell migration, invasion and survival in the presence of its natural ligand in vitro. In this study, we have evaluated the expression of CCR9 and CCL25 in ovarian cancer cells and clinical samples. Ovarian cancer tissue microarrays from University of Alabama at Birmingham and AccuMax were stained for CCR9 and CCL25. Aperio ScanScope was used to acquire 80X digital images and expression analysis of CCR9 and CCL25. Flow cytometry and the Image stream system were used to conform the expression of CCR9 and CCL25 in ovarian cancer cells. Our results show significantly higher (ptumor, dysgerminoma, transitional cell carcinoma, Brenner tumor, yolk sac tumor, adenocarcinoma and fibroma cases, compared to non-neoplastic ovarian tissue. Similar to tissue expression, CCR9 was also significantly expressed by the ovarian cancer cell lines (OVCAR-3 and SK-OV-3) in comparison to normal adult ovarian epithelial cell. We provide the first evidence that CCR9 and its natural ligand CCL25 are highly expressed by ovarian cancer tissue and their expression correlates with histological subtypes. Expression of this chemokine receptor and its ligand CCL25 within primary tumor tissue further suggests a potential role of this chemokine-receptor axis in ovarian cancer progression. PMID:21637913

  12. STRATIGRAPHIC CONTROL ON CCL4 AND CHCL3 CONCENTRATIONS IN THE 200 WEST AREA, HANFORD SITE

    Energy Technology Data Exchange (ETDEWEB)

    Winsor, K.; Last, G.V.

    2008-01-01

    An extensive subsurface contaminant plume of carbon tetrachloride (CCl4) is the focus of a remedial effort in the 200 West Area of the U.S. Department of Energy’s Hanford Site in eastern Washington. Remediation requires a high-resolution understanding of the region’s spatially variable lithofacies and of the effect these lithofacies have on CCl4 migration through the unconfi ned aquifer. To increase the level of detail of our current understanding, a transect was chosen along the primary groundwater fl ow path in the most heavily contaminated area. Borehole logs of wells along this 3.7 km-long transect were standardized and used to create a cross section displaying the depth and continuity of lithofacies. Natural and spectral gamma geophysical logs were examined to pinpoint the depths of geologic units. Depth discrete concentrations of CCl4 and its reductive dechlorination product, chloroform (CHCl3), were overlain on this cross section. Comparison of stratigraphy to contaminant levels shows that peaks in CCl4 concentration occur in thin, fine-grained layers and that other fine-grained layers frequently form lower boundaries to regions of high concentration. Peaks in CCl4 concentrations are frequently located at different depths from those of CHCl3, suggesting that these concentrations are affected by dechlorination of CCl4. Transformation of CCl4 to CHCl3 appears to be more prevalent within reduced, iron-containing sediments. The infl uence of thin, fine-grained layers within the larger aquifer unit indicates that characterization of contamination in this locality should consider subsurface geology with at least as much resolution as provided in this study.

  13. CCL2 Serum Levels and Adiposity Are Associated with the Polymorphic Phenotypes -2518A on CCL2 and 64ILE on CCR2 in a Mexican Population with Insulin Resistance

    OpenAIRE

    Milton-Omar Guzmán-Ornelas; Marcelo Heron Petri; Mónica Vázquez-Del Mercado; Efraín Chavarría-Ávila; Fernanda-Isadora Corona-Meraz; Sandra-Luz Ruíz-Quezada; Perla-Monserrat Madrigal-Ruíz; Jorge Castro-Albarrán; Flavio Sandoval-García; Rosa-Elena Navarro-Hernández

    2016-01-01

    Genetic susceptibility has been described in insulin resistance (IR). Chemokine (C-C motif) ligand-2 (CCL2) is overexpressed in white adipose tissue and is the ligand of C-C motif receptor-2 (CCR2). The CCL2 G-2518A polymorphism is known to regulate gene expression, whereas the physiological effects of the CCR2Val64Ile polymorphism are unknown. The aim of the study is to investigate the relationship between these polymorphisms with soluble CCL2 levels (sCCL2), metabolic markers, and adiposit...

  14. Pulse radiolysis study on the mechanisms of reactions of CCl3OO· radical with quercetin, rutin and epigallocatechin gallate

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The mechanisms of reactions between CCl3OO· radical and quercetin, rutin and epigallocatechin gallate (EGCG) have been studied using pulse radiolytic technique. It is suggested that the electron transfer reaction is the main reaction between CCl3OO· radical and rutin, EGCG, but there are two main pathways for the reaction of CCl3OO· radical with quercetin, one is the electron transfer reaction, the other is addition reaction. The reaction rate constants were determined. It is proved that quercetin and rutin are better CCl3OO· radical scavengers than EGCG.

  15. Differential modulation of retinal degeneration by Ccl2 and Cx3cr1 chemokine signalling.

    Science.gov (United States)

    Luhmann, Ulrich F O; Lange, Clemens A; Robbie, Scott; Munro, Peter M G; Cowing, Jill A; Armer, Hannah E J; Luong, Vy; Carvalho, Livia S; MacLaren, Robert E; Fitzke, Frederick W; Bainbridge, James W B; Ali, Robin R

    2012-01-01

    Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2(-/-)/Crb1(Rd8/RD8), Cx3cr1(-/-)/Crb1(Rd8/RD8) and CCl2(-/-)/Cx3cr1(-/-)/Crb1(Rd8/RD8) mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings

  16. The Effect of rhCygb on CCl4-Induced Hepatic Fibrogenesis in Rat

    Science.gov (United States)

    Li, Zhen; Wei, Wei; Chen, Bohong; Cai, Gaotai; Li, Xin; Wang, Ping; Tang, Jinping; Dong, Wenqi

    2016-01-01

    This study aims to investigate whether the use of recombinant human cytoglobin (rhCygb) impact on hepatic fibrogenesis caused by CCl4. SD (n = 150) rats were randomly divided into three groups of normal, CCl4 model and rhCygb groups. After model establishment, rats in rhCygb groups were administered daily with rhCygb (2 mg/kg, s.c.). Histological lesions were staged according to metavir. Serum parameters including ALT, AST, HA, LN, Col III and Col IV were determined. The liver proteins were separated by 2-DE and identified. As a result, the stage of hepatic damage and liver fibrosis in rhCygb groups were significantly milder than that in CCl4 model groups. Meanwhile, rhCygb dramatically reversed serum levels of ALT and AST, and also markedly decreased the liver fibrosis markers levels of LN, HA, Col III and Col IV. In 2-DE, 33 proteins among three groups with the same changing tendency in normal and rhCygb treated groups compared with CCl4 model group were identified. GO analysis showed that several identified proteins involved in oxidative stress pathway. The study provides new insights and data for administration of rhCygb reversing CCl4-induced liver fibrosis suggesting that rhCygb might be used in the treatment of liver fibrosis. PMID:27006085

  17. Antioxidant Bioactivity of Samsum Ant (Pachycondyla sennaarensis Venom Protects against CCL4-Induced Nephrotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    Hossam Ebaid

    2014-01-01

    Full Text Available To assess whether SAV could influence the effects of carbon tetrachloride (CCL4 exposure, mice were treated with SAV in doses of 100, 200, 300 and 400 μg/kg body weight and the effects on oxidative status and kidney function were studied. Serum levels of creatinine, malondialdehyde (MDA, and blood urea, together with renal and hepatic levels of MDA, glutathione (GSH, superoxide dismutase (SOD, and catalase (CAT were quantified in order to evaluate antioxidant activity. Results showed that the group injected with CCL4 exhibited significantly higher levels of oxidative stress markers, MDA, and significantly lower concentrations of GSH, SOD and catalase. SAV was found to significantly improve these oxidative markers, occasionally, in a dose-dependent manner. Furthermore, treatment with SAV was associated with the same behaviour in respect to kidney functions which had previously been impaired by CCL4. Histopathological examination demonstrated that SAV, in different groups, improved the renal tissue damage induced by CCL4 and histological scores confirmed that significant improvements were obtained after treatment with SAV, particularly with the lowest dose (100 μg/kg body weight. In conclusion, SAV has the potential capability to restore oxidative stability and to improve kidney functions after CCL4 acute injury.

  18. Protective effects of L-carnosine on CCl4 -induced hepatic injury in rats.

    Science.gov (United States)

    Alsheblak, Mehyar Mohammad; Elsherbiny, Nehal M; El-Karef, Amro; El-Shishtawy, Mamdouh M

    2016-03-01

    The present study was undertaken to investigate the possible protective effect of L-carnosine (CAR), an endogenous dipeptide of alanine and histidine, on carbon tetrachloride (CCl4)-induced hepatic injury. Liver injury was induced in male Sprague-Dawley rats by intraperitoneal (i.p.) injections of CCl4, twice weekly for six weeks. CAR was administered to rats daily, at dose of 250 mg/kg, i.p. At the end of six weeks, blood and liver tissue specimens were collected. Results show that CAR treatment attenuated the hepatic morphological changes, necroinflammation and fibrosis induced by CCl4, as indicated by hepatic histopathology scoring. In addition, CAR treatment significantly reduced the CCl4-induced elevation of liver-injury parameters in serum. CAR treatment also combatted oxidative stress; possibly by restoring hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) levels. Moreover, CAR treatment prevented the activation of hepatic stellate cells (HSCs), as indicated by reduced α-smooth muscle actin (α-SMA) expression in the liver, and decreased hepatic inflammation as demonstrated by a reduction in hepatic tumor necrosis factor-α (TNF-α) and restoration of interleukin-10 (IL-10) levels. In conclusion, CCl4-induced hepatic injury was alleviated by CAR treatment. The results suggest that these beneficial, protective effects are due, at least in part, to its anti-oxidant, anti-inflammatory and anti-fibrotic activities. PMID:27094155

  19. Ultrastructural changes in hepatocytes after taurine treatment in CCl4 induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Ilker Tasci; Nuket Has; Mehmet Refik Has; Muwet Tuncer; Bilgin Comert

    2008-01-01

    AIM:To search the organelle based changes in hepatocytes after taurine treatment in experimental liver fibrosis induced by CCl4 administration.METHODS:Thirty rats were divided into two groups.Group 1(η=15)was injected with CCl4 plus taurine and Group 2(η=is)with Ccl4 plus saline for 12 wk.At the end of 12th wk,mitochondria,rough and smooth endoplasmic reticulum,and nuclei of hepatocytes were evaluated using a scoring system.The results were compared with histopathological findings,as well.RESULTS:Taurine treatment reduced fibrosis scores significantly as compared to placebo.Organelle injury scores decreased significantly with taurine treatment.Ultrastructural and hiStopathological scores in both groups were in strong correlation(r=0.931 for CCl4 plus taurine and r=0.899 fOr CCl4 plus saline group).CONCLUSION:Organelle based transmission electron microscopy findings can reflect successfully histological results as well as tissue healing in hepatocytes from hepatotoxin-induced liver fibrosis.

  20. Effect of Platelet-Rich Plasma on CCl4-Induced Chronic Liver Injury in Male Rats.

    Science.gov (United States)

    Hesami, Zahra; Jamshidzadeh, Akram; Ayatollahi, Maryam; Geramizadeh, Bita; Farshad, Omid; Vahdati, Akbar

    2014-01-01

    Platelet-rich plasma (PRP) has been of great concern to the scientists and doctors who are involved in wound healing and regenerative medicine which focuses on repairing and replacing damaged cells and tissues. Growth factors of platelet-rich plasma are cost-effective, available, and is more stable than recombinant human growth factors. Given these valuable properties, we decided to assess the effect of PRP on CCl4-induced hepatotoxicity on rats. The rats received CCl4 (1 mL/kg, i.p. 1 : 1 in olive oil) twice per week for 8 weeks. Five weeks after CCl4 injection, the rats also received PRP (0.5 mL/kg, s.c.) two days a week for three weeks. Twenty-four hours after last CCl4 injection, the animals bled and their livers dissected for biochemical and histopathological studies. Blood analysis was performed to evaluate enzyme activity. The results showed that PRP itself was not toxic for liver and could protect the liver from CCl4-induced histological damages and attenuated oxidative stress by increase in glutathione content and decrease in lipid peroxidative marker of liver tissue. The results of the present study lend support to our beliefs in hepatoprotective effects of PRP. PMID:24707405

  1. The essential oil of Artemisia capillaris protects against CCl4-induced liver injury in vivo

    Directory of Open Access Journals (Sweden)

    Qinghan Gao

    2016-06-01

    Full Text Available Abstract To study the hepatoprotective effect of the essential oil of Artemisia capillaris Thunb., Asteraceae, on CCl4-induced liver injury in mice, the levels of serum aspartate aminotransferase and alanine aminotransferase, hepatic levels of reduced glutathione, activity of glutathione peroxidase, and the activities of superoxide dismutase and malondialdehyde were assayed. Administration of the essential oil of A. capillaris at 100 and 50 mg/kg to mice prior to CCl4 injection was shown to confer stronger in vivo protective effects and could observably antagonize the CCl4-induced increase in the serum alanine aminotransferase and aspartate aminotransferase activities and malondialdehyde levels as well as prevent CCl4-induced decrease in the antioxidant superoxide dismutase activity, glutathione level and glutathione peroxidase activity (p < 0.01. The oil mainly contained β-citronellol, 1,8-cineole, camphor, linalool, α-pinene, β-pinene, thymol and myrcene. This finding demonstrates that the essential oil of A. capillaris can protect hepatic function against CCl4-induced liver injury in mice.

  2. Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4-Induced Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Ping-Chun Li

    2012-01-01

    Full Text Available We used the carbon tetrachloride (CCl4 induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE and silymarin against cardiac hypertrophy. We treated male wistar rats with CCl4 and either OGE (0.02 g/kg B.W. or 0.04 g/kg B.W. or silymarin (0.2 g/kg B.W.. Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6 signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy.

  3. CCL2/MCP-1 modulation of microglial activation and proliferation

    Directory of Open Access Journals (Sweden)

    Garcia-Bueno Borja

    2011-07-01

    Full Text Available Abstract Background Monocyte chemoattractant protein (CCL2/MCP-1 is a chemokine that attracts cells involved in the immune/inflammatory response. As microglia are one of the main cell types sustaining inflammation in brain, we proposed here to analyze the direct effects of MCP-1 on cultured primary microglia. Methods Primary microglia and neuronal cultures were obtained from neonatal and embryonic Wistar rats, respectively. Microglia were incubated with different concentrations of recombinant MCP-1 and LPS. Cell proliferation was quantified by measuring incorporation of bromodeoxyuridine (BrdU. Nitrite accumulation was measured using the Griess assay. The expression and synthesis of different proteins was measured by RT-PCR and ELISA. Cell death was quantified by measuring release of LDH into the culture medium. Results MCP-1 treatment (50 ng/ml, 24 h did not induce morphological changes in microglial cultures. Protein and mRNA levels of different cytokines were measured, showing that MCP-1 was not able to induce proinflammatory cytokines (IL-1β, IL6, MIP-1α, either by itself or in combination with LPS. A similar lack of effect was observed when measuring inducible nitric oxide synthase (NOS2 expression or accumulation of nitrites in the culture media as a different indicator of microglial activation. MCP-1 was also unable to alter the expression of different trophic factors that were reduced by LPS treatment. In order to explore the possible release of other products by microglia and their potential neurotoxicity, neurons were co-cultured with microglia: no death of neurons could be detected when treated with MCP-1. However, the presence of MCP-1 induced proliferation of microglia, an effect opposite to that observed with LPS. Conclusion These data indicate that, while causing migration and proliferation of microglia, MCP-1 does not appear to directly activate an inflammatory response in this cell type, and therefore, other factors may be

  4. CCL2 Serum Levels and Adiposity Are Associated with the Polymorphic Phenotypes -2518A on CCL2 and 64ILE on CCR2 in a Mexican Population with Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Milton-Omar Guzmán-Ornelas

    2016-01-01

    Full Text Available Genetic susceptibility has been described in insulin resistance (IR. Chemokine (C-C motif ligand-2 (CCL2 is overexpressed in white adipose tissue and is the ligand of C-C motif receptor-2 (CCR2. The CCL2 G-2518A polymorphism is known to regulate gene expression, whereas the physiological effects of the CCR2Val64Ile polymorphism are unknown. The aim of the study is to investigate the relationship between these polymorphisms with soluble CCL2 levels (sCCL2, metabolic markers, and adiposity. In a cross-sectional study we included 380 Mexican-Mestizo individuals, classified with IR according to Stern criteria. Polymorphism was identified using PCR-RFLP/sequence-specific primers. Anthropometrics and metabolic markers were measured by routine methods and adipokines and sCCL2 by ELISA. The CCL2 polymorphism was associated with IR (polymorphic A+ phenotype frequencies were 70.9%, 82.6%, in individuals with and without IR, resp.. Phenotype carriers CCL2 (A+ displayed lower body mass and fat indexes, insulin and HOMA-IR, and higher adiponectin levels. Individuals with IR presented higher sCCL2 compared to individuals without IR and was associated with CCR2 (Ile+ phenotype. The double-polymorphic phenotype carriers (A+/Ile+ exhibited higher sCCL2 than double-wild-type phenotype carriers (A−/Ile−. The present findings suggest that sCCL2 production possibly will be associated with the adiposity and polymorphic phenotypes of CCL2 and CCR2, in Mexican-Mestizos with IR.

  5. Endoplasmic Reticulum Stress-induced Overexpression of CCL5 in Human Breast Cancer Cell MCF-7%内质网应激对乳腺癌MCF-7细胞CCL5表达的影响

    Institute of Scientific and Technical Information of China (English)

    范威; 潘翠萍; 张懿敏; 廖仕翀; 魏文; 马彪; 孙圣荣

    2012-01-01

    Objective To discuss the relationship between ER stress and the expression of CCL5 in human breast cancer cell MCF-7 and identify the correlation between CCL5 and the proliferation and metastasis capacity of human breast cancer MCF-7 cells. Methods The ER stress and the expression of CCL5 in the tissue of human breast cancer and adjacent tissue were datected by Western blot. ER stress inducer Tu-niamycin and ER stress inhibitor 4-PBA were used to MCF-7 cells respectively. Samples were collected the total cell protein after 24 hours treatment. Tthe ER stress and the expression of CCL5 in MCF-7 cells was analyzed by Westernblot. The proliferation and metastasis capacity of human breast cancer MCF-7 cells were measured by MTT colorimetry and transwell experiment respectively. ELISA was employed to detect the content of CCL5 in the culture medium. Results The ER stress and the expression of CCL5 in the tissue of human breast cancer were in higher level than that in adjacent tissue. The ER stress of the cells treated with ER stress inducer was in higher level and these cells expressed more CCL5. On the contrary, the ER stress of the cells treated with ER stress inhibitor was in lower level and these cells expressed less CCL5. In addition,the cells treated with ER stress inducer were more proliferative than the cells treated with ER stress inhibitor . CCL5 secreted to the culture medium could enhance the capacity of proliferation and metastasis of human breast cancer MCF-7 cells. Conclution ER stress can induce the endogenous expression of CCL5 in MCF-7 cells. Endogenous CCL5 can promote the proliferation of human breast cancer MCF-7 cells and extraneous CCL5 can promote the metastasis of MCF-7 cells.%目的 探讨内质网应激水平与人乳腺癌MCF-7细胞CCL5表达之间的关系,明确CCL5与人乳腺癌MCF-7细胞增殖侵袭转移能力之间的关系.方法 使用内质网应激诱导剂(Tuniamycin)和内质网应激抑制剂(4-PBA)分别处理人乳腺癌MCF-7

  6. PROTECTIVE EFFECT OF Solanum Pubescens LINN ON CCL4 INDUCED HEPATOTOXICITY IN ALBINO RATS

    Directory of Open Access Journals (Sweden)

    M.Pushpalatha

    2012-01-01

    Full Text Available Ethanol extract of Solanum pubescens Linn was evaluated for hepato protective and antioxidant activities in rats. The plant extract (500mg/kg/day showed a remarkable hepatoprotective and antioxidant activity against Carbon tetrachloride (CCl4-induced hepatotoxicity as judged from the serum marker enzymes and antioxidant levels in liver tissues. CCl4 induced a significant rise in aspartate amino transferase (AST, alanine amino transferase (ALT, alkaline phosphatase (ALP, total bilirubin, LPO with a reduction of total protein, superoxide dismutase (SOD, catalase, and reduced glutathione (GSH. Treatment of rats with plant extract (500 mg/kg significantly (P<0.01 altered serum marker enzymes and antioxidant levels to near normal against CCl4 - treated rats. The activity of the extract at dose of 500 mg/kg was comparable to the standard drug, Silymarin (50 mg/kg, p.o.. Histopathological examination of the liver tissues supported the hepatoprotective activity of plant.

  7. The electron-impact dissociative ionization of CCl{sub 2}F{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Sierra, Borja [Departamento de QuImica FIsica, Universidad del PaIs Vasco, Facultad de Ciencias, Apartado 644, 48080 Bilbao (Spain); MartInez, Roberto [Departamento de QuImica FIsica, Universidad del PaIs Vasco, Facultad de Ciencias, Apartado 644, 48080 Bilbao (Spain); Castano, Fernando [Departamento de QuImica FIsica, Universidad del PaIs Vasco, Facultad de Ciencias, Apartado 644, 48080 Bilbao (Spain)

    2004-01-14

    An investigation of the formation channels and properties of ion fragments following electron-impact dissociative ionization of the CCl{sub 2}F{sub 2} molecule using electron kinetic energies in the 0-100 eV range is reported. Measurements of ion appearance potentials (APs) and nascent translational energy distributions were made on a supersonic expansion of CCl{sub 2}F{sub 2} in a time-of-flight mass spectrometer. A discussion of the correlation between the channel APs, the precursor bond characters as calculated from the population analysis, and the low-resolution photoelectron spectrum of the CCl{sub 2}F{sub 2} molecule is presented.

  8. Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, T.L.; Sellebjerg, F; Jensen, C.V.;

    2001-01-01

    . Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls....... The levels of CXCL10 were higher in the patient group than in controls but two outliers in the control group also had high CSF concentrations of CXCL10. The CSF concentrations of CXCL10 did not change over time or after treatment. The CSF concentration of CXCL10 was positively correlated with the CSF...... and IgG synthesis levels. CXCL10 may be involved in the maintenance of intrathecal inflammation whereas CCL2 correlates negatively with measures of inflammation, suggesting differential involvement of CXCL10 and CCL2 in CNS inflammation...

  9. Importance of the CCR5-CCL5 axis for mucosal Trypanosoma cruzi protection and B cell activation.

    Science.gov (United States)

    Sullivan, Nicole L; Eickhoff, Christopher S; Zhang, Xiuli; Giddings, Olivia K; Lane, Thomas E; Hoft, Daniel F

    2011-08-01

    Trypanosoma cruzi is an intracellular parasite and the causative agent of Chagas disease. Previous work has shown that the chemokine receptor CCR5 plays a role in systemic T. cruzi protection. We evaluated the importance of CCR5 and CCL5 for mucosal protection against natural oral and conjunctival T. cruzi challenges. T. cruzi-immune CCR5(-/-) and wild-type C57BL/6 mice were generated by repeated infectious challenges with T. cruzi. CCR5(-/-) and wild-type mice developed equivalent levels of cellular, humoral, and protective mucosal responses. However, CCR5(-/-)-immune mice produced increased levels of CCL5 in protected gastric tissues, suggesting compensatory signaling through additional receptors. Neutralization of CCL5 in CCR5(-/-)-immune mice resulted in decreased mucosal inflammatory responses, reduced T. cruzi-specific Ab-secreting cells, and significantly less mucosal T. cruzi protection, confirming an important role for CCL5 in optimal immune control of T. cruzi replication at the point of initial mucosal invasion. To investigate further the mechanism responsible for mucosal protection mediated by CCL5-CCR5 signaling, we evaluated the effects of CCL5 on B cells. CCL5 enhanced proliferation and IgM secretion in highly purified B cells triggered by suboptimal doses of LPS. In addition, neutralization of endogenous CCL5 inhibited B cell proliferation and IgM secretion during stimulation of highly purified B cells, indicating that B cell production of CCL5 has important autocrine effects. These findings demonstrate direct effects of CCL5 on B cells, with significant implications for the development of mucosal adjuvants, and further suggest that CCL5 may be important as a general B cell coactivator.

  10. Protective Effect of Procyanidin B2 against CCl4-Induced Acute Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Bing-Ya Yang

    2015-07-01

    Full Text Available Procyanidin B2 has demonstrated several health benefits and medical properties. However, its protective effects against CCl4-induced hepatotoxicity have not been clarified. The present study aimed to investigate the hepatoprotective effects of procyanidin B2 in CCl4-treated mice. Our data showed that procyanidin B2 significantly decreased the CCl4-induced elevation of serum alanine aminotransferase activities, as well as improved hepatic histopathological abnormalities. Procyanidin B2 also significantly decreased the content of MDA but enhanced the activities of antioxidant enzymes SOD, CAT and GSH-Px. Further research demonstrated that procyanidin B2 decreased the expression of TNF-α, IL-1β, cyclooxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS, as well as inhibited the translocation of nuclear factor-kappa B (NF-κB p65 from the cytosol to the nuclear fraction in mouse liver. Moreover, CCl4-induced apoptosis in mouse liver was measured by (terminal-deoxynucleotidyl transferase mediated nick end labeling TUNEL assay and the cleaved caspase-3. Meanwhile, the expression of apoptosis-related proteins Bax and Bcl-xL was analyzed by Western blot. Results showed that procyanidin B2 significantly inhibited CCl4-induced hepatocyte apoptosis, markedly suppressed the upregulation of Bax expression and restored the downregulation of Bcl-xL expression. Overall, the findings indicated that procyanidin B2 exhibited a protective effect on CCl4-induced hepatic injury by elevating the antioxidative defense potential and consequently suppressing the inflammatory response and apoptosis of liver tissues.

  11. Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment.

    Science.gov (United States)

    Hong, Gyong Hwa; Kwon, Hyouk-Soo; Moon, Keun-Ai; Park, So Young; Park, Sunjoo; Lee, Kyoung Young; Ha, Eun Hee; Kim, Tae-Bum; Moon, Hee-Bom; Lee, Heung Kyu; Cho, You Sook

    2016-03-01

    Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway. PMID:26826245

  12. Interaction of the selectin ligand PSGL-1 with chemokines CCL21 and CCL19 facilitates efficient homing of T cells to secondary lymphoid organs.

    Science.gov (United States)

    Veerman, Krystle M; Williams, Michael J; Uchimura, Kenji; Singer, Mark S; Merzaban, Jasmeen S; Naus, Silvia; Carlow, Douglas A; Owen, Philip; Rivera-Nieves, Jesús; Rosen, Steven D; Ziltener, Hermann J

    2007-05-01

    P-selectin glycoprotein ligand 1 (PSGL-1) is central to the trafficking of immune effector cells to areas of inflammation through direct interactions with P-selectin, E-selectin and L-selectin. Here we show that PSGL-1 was also required for efficient homing of resting T cells to secondary lymphoid organs but functioned independently of selectin binding. PSGL-1 mediated an enhanced chemotactic T cell response to the secondary lymphoid organ chemokines CCL21 and CCL19 but not to CXCL12 or to inflammatory chemokines. Our data show involvement of PSGL-1 in facilitating the entry of T cells into secondary lymphoid organs, thereby demonstrating the bifunctional nature of this molecule.

  13. Variation in CCL3L1 copy number in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Taormina, Patrick L; Satkoski Trask, Jessica A; Smith, David G; Kanthaswamy, Sreetharan

    2012-06-01

    We used real-time quantitative PCR (qPCR) methodology to examine copy number variation (CNV) of the CCL3L1 gene among pure Indian-origin, pure Chinese-origin, and hybrid Indian-Chinese rhesus macaques (Macaca mulatta). CNV among purebred macaques fell within expected ranges, with Indian macaques having lower copy numbers than those of Chinese macaques. Compared with the purebred macaques, Indian-Chinese hybrid rhesus macaques showed much greater variance in copy number and an intermediate average copy number. Copy numbers of CCL3L1 in rhesus macaque trios (sire, dam, and offspring) were consistent with Mendelian inheritance. PMID:22776055

  14. Hepatoprotective activity of cinnamon ethanolic extract against CCl4-induced liver injury in rats

    OpenAIRE

    Bazargan, Maryam; Eidi, Akram; MORTAZAVI, Pejman; Zaringalam, Jalal

    2012-01-01

    The inner bark of cinnamon (Cinnamomum zeylanicum L.) is commonly used as a spice and has also been widely employed in the treatment and prevention of disease. The aim of the present study is to evaluate the protective effect of cinnamon bark extract against carbon tetrachloride (CCl4)-induced liver damage in male Wistar rats. Administration with cinnamon extracts (0.01, 0.05 and 0.1 g/kg) for 28 days significantly reduced the impact of CCl4 toxicity on the serum markers of liver damage, ...

  15. Inhibitory effect of Newcastle disease virus on hepatic fibrosis induced by CCl4

    OpenAIRE

    Ya-lin LI

    2013-01-01

    Objective To explore the inhibitory effect of Newcastle diseases virus (NDV) on CCl4-induced liver fibrosis in mice. Methods Liver fibrosis model was reproduced in 30 Kunming mice by intraperitoneal injection of CCl4/peanut oil solution for 2 times a week, and the total treatment lasted for 8 weeks. Three days after last injection, NDV was injected through tail vein for 1 or 3 times (24h intervals). Twenty-four hours after NDV infusion, mice were sacrificed and the livers were removed for gro...

  16. Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1β and CCL2/MCP-1 in dengue fever and parvovirosis

    Directory of Open Access Journals (Sweden)

    Luzia Maria de-Oliveira-Pinto

    2012-02-01

    Full Text Available Dengue virus (DENV and parvovirus B19 (B19V infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL-1 receptor antagonist (Ra, CXCL10/inducible protein-10 (IP-10, CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1 were determined by multiplex immunoassay in serum samples obtained from B19V (37 and DENV-infected (36 patients and from healthy individuals (7. Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1β, while CXCL10/IP-10 was confirmed as a strong pro-inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients.

  17. Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1β and CCL2/MCP-1 in dengue fever and parvovirosis.

    Science.gov (United States)

    de-Oliveira-Pinto, Luzia Maria; Gandini, Mariana; Freitas, Laís Picinini; Siqueira, Marilda Mendonça; Marinho, Cíntia Ferreira; Setúbal, Sérgio; Kubelka, Claire Fernandes; Cruz, Oswaldo Gonçalves; Oliveira, Solange Artimos de

    2012-02-01

    Dengue virus (DENV) and parvovirus B19 (B19V) infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL)-1 receptor antagonist (Ra), CXCL10/inducible protein-10 (IP-10), CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1) were determined by multiplex immunoassay in serum samples obtained from B19V (37) and DENV-infected (36) patients and from healthy individuals (7). Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1β, while CXCL10/IP-10 was confirmed as a strong pro-inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients.

  18. The biofunction of orange-spotted grouper (Epinephelus coioides) CC chemokine ligand 4 (CCL4) in innate and adaptive immunity.

    Science.gov (United States)

    Hsu, Yi-Jiou; Hou, Chia-Yi; Lin, Shih-Jie; Kuo, Wan-Ching; Lin, Han-Tso; Lin, John Han-You

    2013-12-01

    CC chemokine (motif) ligand 4 (CCL4) is indispensable to the chemoattraction of macrophages, natural killer cells, and lymphocytes in mammals; however, it has only been cloned in a limited number of fish species and information related to its biofunction remains ambiguous with regard to teleosts. To explore the role of teleost CCL4, we first evaluated the mRNA expression of the Epinephelus coioides CCL4 (gCCL4) gene in various organs under LPS and poly (I:C) stimulated; secondary, we evaluated the immune-related genes expression of fish under the recombinant gCCL4 protein stimulated. Our results revealed an increase in the mRNA of gCCL4 in immune organs immediately following stimulation by poly (I:C); however, in LPS stimulated fish, the expression did not increase until nearly 24 h after induction. In biofunction assays, recombinant gCCL4 was found to induce chemotactic activity in the peripheral blood leukocytes of groupers and up-regulate the gene expressions of grouper TNFA1 (TNF-α1), TNFA2 (TNF-α2), IFNG (IFN-γ), MX, TBX21 (T-bet), CD8 (α and β chain). These findings indicate that grouper CCL4 attracts leukocytes, induces an inflammatory response, and drives lymphocyte differentiation into the Th1 pathway.

  19. CCL21-induced calcium transients and proliferation in primary mouse astrocytes : CXCR3-dependent and independent responses

    NARCIS (Netherlands)

    van Weering, Hilmar R. J.; de Jong, Arthur P. H.; de Haas, Alexander H.; Biber, Knut P. H.; Boddeke, Hendrikus W. G. M.

    2010-01-01

    CCL21 is a homeostatic chemokine that is expressed constitutively in secondary lymph nodes and attracts immune cells via chemokine receptor CCR7. In the brain however, CCL21 is inducibly expressed in damaged neurons both in vitro and in vivo and has been shown to activate microglia in vitro, albeit

  20. Chicory (Cichorium intybus L.) root extract regulates the oxidative status and antioxidant gene transcripts in CCl4-induced hepatotoxicity.

    Science.gov (United States)

    El-Sayed, Yasser S; Lebda, Mohamed A; Hassinin, Mohammed; Neoman, Saad A

    2015-01-01

    The ability of Cichorium intybus root extract (chicory extract) to protect against carbon tetrachloride (CCl4)-induced oxidative stress and hepatotoxicity was evaluated in male rats. The rats were divided into four groups according to treatment: saline (control); chicory extract (100 mg/kg body weight daily, given orally for 2 weeks); CCl4 (1 ml/kg body weight by intraperitoneal injection for 2 consecutive days only); or chicory extract (100 mg/kg body weight daily for 2 weeks) + CCl4 injection on days 16 and 17. The levels of hepatic lipid peroxidation, antioxidants, and molecular biomarkers were estimated twenty-four hours after the last CCl4 injection. Pretreatment with chicory extract significantly reduced CCl4-induced elevation of malondialdehyde levels and nearly normalized levels of glutathione and activity of glutathione S-transferase, glutathione peroxidase (GPx), glutathione reductase, catalase (CAT), paraoxonase-1 (PON1), and arylesterase in the liver. Chicory extract also attenuated CCl4-induced downregulation of hepatic mRNA expression levels of GPx1, CAT and PON1 genes. Results of DNA fragmentation support the ability of chicory extract to ameliorate CCl4-induced liver toxicity. Taken together, our results demonstrate that chicory extract is rich in natural antioxidants and able to attenuate CCl4-induced hepatocellular injury, likely by scavenging reactive free radicals, boosting the endogenous antioxidant defense system, and overexpressing genes encoding antioxidant enzymes. PMID:25807561

  1. Chicory (Cichorium intybus L. root extract regulates the oxidative status and antioxidant gene transcripts in CCl4-induced hepatotoxicity.

    Directory of Open Access Journals (Sweden)

    Yasser S El-Sayed

    Full Text Available The ability of Cichorium intybus root extract (chicory extract to protect against carbon tetrachloride (CCl4-induced oxidative stress and hepatotoxicity was evaluated in male rats. The rats were divided into four groups according to treatment: saline (control; chicory extract (100 mg/kg body weight daily, given orally for 2 weeks; CCl4 (1 ml/kg body weight by intraperitoneal injection for 2 consecutive days only; or chicory extract (100 mg/kg body weight daily for 2 weeks + CCl4 injection on days 16 and 17. The levels of hepatic lipid peroxidation, antioxidants, and molecular biomarkers were estimated twenty-four hours after the last CCl4 injection. Pretreatment with chicory extract significantly reduced CCl4-induced elevation of malondialdehyde levels and nearly normalized levels of glutathione and activity of glutathione S-transferase, glutathione peroxidase (GPx, glutathione reductase, catalase (CAT, paraoxonase-1 (PON1, and arylesterase in the liver. Chicory extract also attenuated CCl4-induced downregulation of hepatic mRNA expression levels of GPx1, CAT and PON1 genes. Results of DNA fragmentation support the ability of chicory extract to ameliorate CCl4-induced liver toxicity. Taken together, our results demonstrate that chicory extract is rich in natural antioxidants and able to attenuate CCl4-induced hepatocellular injury, likely by scavenging reactive free radicals, boosting the endogenous antioxidant defense system, and overexpressing genes encoding antioxidant enzymes.

  2. Blood-brain barrier disruption in CCL2 transgenic mice during pertussis toxin-induced brain inflammation

    DEFF Research Database (Denmark)

    Schellenberg, Angela E; Buist, Richard; Del Bigio, Marc R;

    2012-01-01

    ABSTRACT: BACKGROUND: The chemokine CCL2 has an important role in the recruitment of inflammatory cells into the central nervous system (CNS). A transgenic mouse model that overexpresses CCL2 in the CNS shows an accumulation of leukocytes within the perivascular space surrounding vessels, which i...

  3. Expression of CCL21 in Ewing sarcoma shows an inverse correlation with metastases and is a candidate target for immunotherapy.

    Science.gov (United States)

    Sand, Laurens G L; Berghuis, Dagmar; Szuhai, Karoly; Hogendoorn, Pancras C W

    2016-08-01

    Ewing sarcoma is an aggressive neoplasm predominantly occurring in adolescents and has a poor prognosis when metastasized. For patients with metastatic disease in particular, immunotherapy has been proposed as possible beneficial additive therapy. CCL21 activation-based immunotherapy was successful in preclinical studies in other tumor types; therefore, we investigated CCL21 expression in Ewing sarcoma as potential target for immunotherapy. The CCL21 RNA expression was determined in 21 Ewing sarcoma cell lines and 18 primary therapy-naive Ewing sarcoma samples. In the tumor samples, this was correlated with the number and CD4(+)/CD8(+) ratio of infiltrating T cells and clinical parameters. Higher RNA expression levels of CCL21 significantly correlated with a lower CD4(+)/CD8(+) T cell ratio (P = 0.009), good chemotherapeutic response (P = 0.01) and improved outcome (P factor. Protein expression analysis of CCL21 and its receptor CCR7 in 24 therapy-naïve tumors showed that there was no expression in all bar one Ewing sarcoma cells. In conclusion, CCL21 is expressed in clinical Ewing sarcoma samples by nontumor-infiltrating immune cells. The observed positive correlation with survival implies that CCL21 might be a potential prognostic marker for Ewing sarcoma and marks the potential of CCL21 immunotherapy for use in Ewing sarcoma. PMID:27369431

  4. Inhibition of CCL2 Signaling in Combination with Docetaxel Treatment Has Profound Inhibitory Effects on Prostate Cancer Growth in Bone

    Directory of Open Access Journals (Sweden)

    Eva Corey

    2013-05-01

    Full Text Available The C-C chemokine ligand 2 (CCL2 stimulates migration, proliferation, and invasion of prostate cancer (PCa cells, and its signaling also plays a role in the activation of osteoclasts. Therefore targeting CCL2 signaling in regulation of tumor progression in bone metastases is an area of intense research. The objective of our study was to investigate the efficacy of CCL2 blockade by neutralizing antibodies to inhibit the growth of PCa in bone. We used a preclinical model of cancer growth in the bone in which PCa C4-2B cells were injected directly into murine tibiae. Animals were treated for ten weeks with neutralizing anti-CCL2 antibodies, docetaxel, or a combination of both, and then followed an additional nine weeks. CCL2 blockade inhibited the growth of PCa in bone, with even more pronounced inhibition in combination with docetaxel. CCL2 blockade also resulted in increases in bone mineral density. Furthermore, our results showed that the tumor inhibition lasted even after discontinuation of the treatment. Our data provide compelling evidence that CCL2 blockade slows PCa growth in bone, both alone and in combination with docetaxel. These results support the continued investigations of CCL2 blockade as a treatment for advanced metastatic PCa.

  5. Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria.

    LENUS (Irish Health Repository)

    Sibartie, Shomik

    2009-01-01

    BACKGROUND: Human intestinal epithelial cells (IECs) secrete the chemokine CCL20 in response to infection by various enteropathogenic bacteria or exposure to bacterial flagellin. CCL20 recruits immature dendritic cells and lymphocytes to target sites. Here we investigated IEC responses to various pathogenic and commensal bacteria as well as the modulatory effects of commensal bacteria on pathogen-induced CCL20 secretion. HT-29 human IECs were incubated with commensal bacteria (Bifidobacterium infantis or Lactobacillus salivarius), or with Salmonella typhimurium, its flagellin, Clostridium difficile, Mycobacterium paratuberculosis, or Mycobacterium smegmatis for varying times. In some studies, HT-29 cells were pre-treated with a commensal strain for 2 hr prior to infection or flagellin stimulation. CCL20 and interleukin (IL)-8 secretion and nuclear factor (NF)-kappaB activation were measured using enzyme-linked immunosorbent assays. RESULTS: Compared to untreated cells, S. typhimurium, C. difficile, M. paratuberculosis, and flagellin activated NF-kappaB and stimulated significant secretion of CCL20 and IL-8 by HT-29 cells. Conversely, B. infantis, L. salivarius or M. smegmatis did not activate NF-kappaB or augment CCL20 or IL-8 production. Treatment with B. infantis, but not L. salivarius, dose-dependently inhibited the baseline secretion of CCL20. In cells pre-treated with B. infantis, C. difficile-, S. typhimurium-, and flagellin-induced CCL20 were significantly attenuated. B. infantis did not limit M. Paratuberculosis-induced CCL20 secretion. CONCLUSION: This study is the first to demonstrate that a commensal strain can attenuate CCL20 secretion in HT-29 IECs. Collectively, the data indicate that M. paratuberculosis may mediate mucosal damage and that B. infantis can exert immunomodulatory effects on IECs that mediate host responses to flagellin and flagellated enteric pathogens.

  6. CCL2 is associated with a faster rate of cognitive decline during early stages of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Karin Westin

    Full Text Available Chemokine (C-C motif receptor 2 (CCR2-signaling can mediate accumulation of microglia at sites affected by neuroinflammation. CCR2 and its main ligand CCL2 (MCP-1 might also be involved in the altered metabolism of beta-amyloid (Aβ underlying Alzheimer's disease (AD. We therefore measured the levels of CCL2 and three other CCR2 ligands, i.e. CCL11 (eotaxin, CCL13 (MCP-4 and CCL26 (eotaxin-3, in the cerebrospinal fluid (CSF and plasma of 30 controls and 119 patients with mild cognitive impairment (MCI at baseline. During clinical follow-up 52 MCI patients were clinically stable for five years, 47 developed AD (i.e. cases with prodromal AD at baseline and 20 developed other dementias. Only CSF CCL26 was statistically significantly elevated in patients with prodromal AD when compared to controls (p = 0.002. However, in patients with prodromal AD, the CCL2 levels in CSF at baseline correlated with a faster cognitive decline during follow-up (r(s = 0.42, p = 0.004. Furthermore, prodromal AD patients in the highest tertile of CSF CCL2 exhibited a significantly faster cognitive decline (p<0.001 and developed AD dementia within a shorter time period (p<0.003 compared to those in the lowest tertile. Finally, in the entire MCI cohort, CSF CCL2 could be combined with CSF Tau, P-tau and Aβ42 to predict both future conversion to AD and the rate of cognitive decline. If these results are corroborated in future studies, CCL2 in CSF could be a candidate biomarker for prediction of future disease progression rate in prodromal AD. Moreover, CCR2-related signaling pathways might be new therapeutic targets for therapies aiming at slowing down the disease progression rate of AD.

  7. A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs.

    Directory of Open Access Journals (Sweden)

    Kristi Huik

    Full Text Available The role of CC chemokine receptor 5 (CCR5 and its ligand CCL5 on the pathogenesis of HIV infection has been well studied but not for HCV infection. Here, we investigated whether CCL5 haplotypes influence HIV and HCV seropositivity among 373 Caucasian people who inject drugs (PWID from Estonia.Study included 373 PWID; 56% were HIV seropositive, 44% HCV seropositive and 47% co-infected. Four CCL5 haplotypes (A-D were derived from three CCL5 polymorphisms (rs2107538/rs2280788/rs2280789 typed by Taqman allelic discrimination assays. The data of CCR5 haplotypes were used from our previous study. The association between CCL5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis.Possessing CCL5 haplotype D (defined by rs2107538A/rs2280788G/rs2280789C decreased the odds of HCV seropositivity compared to those not possessing it (OR = 0.19; 95% CI 0.09-0.40, which remained significant after adjustment to co-variates (OR = 0.08; 95% CI 0.02-0.29. An association of this haplotype with HIV seropositivity was not found. In step-wise logistic regression with backward elimination CCL5 haplotype D and CCR5 HHG*1 had reduced odds for HCV seropositivity (OR = 0.28 95% CI 0.09-0.92; OR = 0.23 95% CI 0.08-0.68, respectively compared to those who did not possess these haplotypes, respectively.Our results suggest that among PWID CCL5 haplotype D and CCR5 HHG*1 independently protects against HCV. Our findings highlight the importance of CCL5 genetic variability and CCL5-CCR5 axis on the susceptibility to HCV.

  8. Effect of extracts from araticum (Annona crassiflora on CCl4-induced liver damage in rats

    Directory of Open Access Journals (Sweden)

    Roberta Roesler

    2011-03-01

    Full Text Available The influence of ethanolic extracts of Annona crassiflora on the activities of hepatic antioxidant enzymes was examined. Extracts of A. crassiflora seeds and peel were administered orally (50 mg of galic acid equivalents.kg-1 to Wistar rats for 14 consecutive days followed by a single oral dose of carbon tetrachloride (CCl4, 2 g.kg-1. Lipid peroxidation and the activities of hepatic catalase (CAT, cytochromes P450 (CP450 and b5, glutathione peroxidase (GPx, glutathione reductase (GRed, superoxide dismutase (SOD, and the content of glutathione equivalents (GSH were evaluated. The treatment with CCl4 increased lipid peroxidation, the level of GSH equivalents and the content of cytochrome b5 by 44, 140 and 32%, respectively, with concomitant reductions of 23, 34 and 39% in the activities of CAT, SOD, and CP450, respectively. The treatment with A. crassiflora seeds and peel extracts alone inhibited lipid peroxidation by 27 and 22%, respectively without affecting the CP450 content. The pretreatment with the A. crassiflora extracts prevented the lipid peroxidation, the increase in GSH equivalents and the decrease in CAT activity caused by CCl4, but it had no effect on the CCl4-mediated changes in CP450 and b5 and SOD. These results show that A. crassiflora seeds and peel contain antioxidant activity in vivo that could be of potential therapeutic use.

  9. Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases

    Institute of Scientific and Technical Information of China (English)

    Claudia Rubie; Vilma Oliveira Frick; Pirus Ghadjar; Mathias Wagner; Christoph Justinger; Stefan Graeber; Jens Sperling; Otto Kollmar; Martin K Schilling

    2011-01-01

    AIM: To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage Ⅳ colorectal cancer (CRC) patients. METHODS: Using Real Time-PCR, enzyme-linked immunosorbent assay, Western Blots and immunohistochemistry, we have analyzed the expression of CCL20, CCR6 and proliferation marker Ki-67 in colorectal liver metastasis (CRLM) specimens from stage Ⅳ CRC patients who received preoperative FOLFOX chemotherapy (n = 53) and in patients who did not receive FOLFOX chemotherapy prior to liver surgery (n = 29). RESULTS: Of the 53 patients who received FOLFOX, time to liver surgery was ≤ 1 mo in 14 patients, ≤ 1 year in 22 patients and > 1 year in 17 patients, respectively. In addition, we investigated the proliferation rate of CRC cells in liver metastases in the different patient groups. Both CCL20 and CCR6 mRNA and protein expression levels were significantly increased in patients who received preoperative FOLFOX chemotherapy ≤ 12 mo before liver surgery (P < 0.001) in comparison to patients who did not undergo FOLFOX treatment. Further, proliferation of CRLM cells as measured by Ki-67 was increased in patients who underwent FOLFOX treatment. CCL20 and CCR6 expression levels were significantly increased in CRLM patients who had undergone preoperative FOLFOX chemotherapy. CONCLUSION: This chemokine/receptor up-regulation could lead to increased proliferation/migration through an autocrine mechanism which might be used by surviving metastatic cells to escape cell death caused by FOLFOX.

  10. Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity

    Science.gov (United States)

    Trivedi, Palak J.; Bruns, Tony; Ward, Stephen; Mai, Martina; Schmidt, Carsten; Hirschfield, Gideon M.; Weston, Chris J.; Adams, David H.

    2016-01-01

    CCL25-mediated activation of CCR9 is critical for mucosal lymphocyte recruitment to the intestine. In immune-mediated liver injury complicating inflammatory bowel disease, intrahepatic activation of this pathway allows mucosal lymphocytes to be recruited to the liver, driving hepatobiliary destruction in primary sclerosing cholangitis (PSC). However, in mice and healthy humans CCL25 expression is restricted to the small bowel, whereas few data exist on activation of this pathway in the inflamed colon despite the vast majority of PSC patients having ulcerative colitis. Herein, we show that colonic CCL25 expression is not only upregulated in patients with active colitis, but strongly correlates with endoscopic Mayo score and mucosal TNFα expression. Moreover, approximately 90% (CD4+) and 30% (CD8+) of tissue-infiltrating T-cells in colitis were identified as CCR9+ effector lymphocytes, compared to <10% of T-cells being CCR9+ in normal colon. Sorted CCR9+ lymphocytes also demonstrated enhanced cellular adhesion to stimulated hepatic sinusoidal endothelium compared with their CCR9– counterparts when under flow. Collectively, these results suggest that CCR9/CCL25 interactions are not only involved in colitis pathogenesis but also correlate with colonic inflammatory burden; further supporting the existence of overlapping mucosal lymphocyte recruitment pathways between the inflamed colon and liver. PMID:26873648

  11. Antioxidant and protective effect of inulin and catechin grafted inulin against CCl4-induced liver injury.

    Science.gov (United States)

    Liu, Jun; Lu, Jian-feng; Wen, Xiao-yuan; Kan, Juan; Jin, Chang-hai

    2015-01-01

    In this study, the antioxidant activity and hepatoprotective effect of inulin and catechin grafted inulin (catechin-g-inulin) against carbon tetrachloride (CCl4)-induced acute liver injury were investigated. Results showed that both inulin and catechin-g-inulin had moderate scavenging activity on superoxide radical, hydroxyl radical and H2O2, as well as lipid peroxidation inhibition effect. The antioxidant activity decreased in the order of Vc > catechin >catechin-g-inulin > inulin. Administration of inulin and catechin-g-inulin could significantly reduce the elevated levels of serum aspartate transaminase, alanine transaminase and alkaline phosphatase as compared to CCl4 treatment group. Moreover, inulin and catechin-g-inulin significantly increased the levels of hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione and total antioxidant capacity, whereas markedly decreased the malondialdehyde level when compared with CCl4 treatment group. Notably, catechin-g-inulin showed higher hepatoprotective effect than inulin. In addition, the hepatoprotective effect of catechin-g-inulin was comparable to positive standard of silymarin. Our results suggested that catechin-g-inulin had potent antioxidant activity and potential protective effect against CCl4-induced acute liver injury.

  12. Extreme 13C depletion of CCl2F2 in firn air samples from NEEM, Greenland

    NARCIS (Netherlands)

    Zuiderweg, A.T.; Holzinger, R.; Röckmann, T.

    2012-01-01

    A series of 12 high volume air samples collected from the S2 firn core during the North Greenland Eemian Ice Drilling (NEEM) 2009 campaign have been measured for mixing ratio and stable carbon isotope composition of the chlorofluorocarbon CFC- 12 (CCl2F2). While the mixing ratio measurements compare

  13. Inhibitory effect of Newcastle disease virus on hepatic fibrosis induced by CCl4

    Directory of Open Access Journals (Sweden)

    Ya-lin LI

    2013-11-01

    Full Text Available Objective To explore the inhibitory effect of Newcastle diseases virus (NDV on CCl4-induced liver fibrosis in mice. Methods Liver fibrosis model was reproduced in 30 Kunming mice by intraperitoneal injection of CCl4/peanut oil solution for 2 times a week, and the total treatment lasted for 8 weeks. Three days after last injection, NDV was injected through tail vein for 1 or 3 times (24h intervals. Twenty-four hours after NDV infusion, mice were sacrificed and the livers were removed for gross morphology observation. The liver tissue sections were stained by HE and Sirius red dyeing. α-smooth muscle actin (α-SMA expression was detected by Western blotting. Results After CCl4 induction for 8 weeks, obvious fibrosis symptoms appeared in the liver of model mice, and the surface of liver tissue became hard with rough, with white patches on it. HE staining showed that there was loosening of tissue and enlarged perisinusoidal spaces in liver with fibrosis. Sirius red dyeing displayed abnormal collagen deposition in the fibrotic liver tissues. After NDV injection for 3 times, white spots on the surface of mouse liver were significantly reduced, and collagen deposition was lowered. Western blotting showed that α-SMA levels decreased with increasing frequency of NDV injection. Conclusion NDV may effectively suppress the development of CCl4-induced liver fibrosis in mice. DOI: 10.11855/j.issn.0577-7402.2013.11.003

  14. Minocycline, a microglial inhibitor, blocks spinal CCL2-induced heat hyperalgesia and augmentation of glutamatergic transmission in substantia gelatinosa neurons

    Science.gov (United States)

    2014-01-01

    Background Several lines of evidence suggest that CCL2 could initiate the hyperalgesia of neuropathic pain by causing central sensitization of spinal dorsal horn neurons and facilitating nociceptive transmission in the spinal dorsal horn. The cellular and molecular mechanisms by which CCL2 enhances spinal pain transmission and causes hyperalgesia remain unknown. The substantia gelatinosa (lamina II) of the spinal dorsal horn plays a critical role in nociceptive transmission. An activated spinal microglia, which is believed to release pro-inflammatory cytokines including TNF-α, plays an important role in the development of neuropathic pain, and CCL2 is a key mediator for spinal microglia activation. In the present study, we tested the hypothesis that spinal CCL2 causes the central sensitization of substantia gelatinosa neurons and enhances spinal nociceptive transmission by activating the spinal microglia and augmenting glutamatergic transmission in lamina II neurons. Methods CCL2 was intrathecally administered to 2-month-old male rats. An intrathecal injection of CCL2 induced heat hyperalgesia, which was assessed using the hot plate test. Whole-cell voltage-clamp recordings substantia gelatinosa neurons in spinal cord slices were performed to record glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs). Results The hot plate test showed that 1 day after the intrathecal injection of CCL2 (1 μg), the latency of hind-paw withdrawal caused by a heat stimulus was significantly reduced in rats. One day after the intrathecal administration of CCL2, the amplitude of the evoked glutamatergic EPSCs and the frequency of spontaneous glutamatergic miniature EPSCs (mEPSCs) were significantly increased in outer lamina II neurons. Intrathecal co-injection of minocycline, a specific inhibitor of microglial activation, and CCL2 blocked the CCL2-induced reduction in the latency of hind-paw withdrawal and thermal hyperalgesia

  15. Adaptive Gene Loss? Tracing Back the Pseudogenization of the Rabbit CCL8 Chemokine.

    Science.gov (United States)

    van der Loo, Wessel; Magalhaes, Maria João; de Matos, Ana Lemos; Abrantes, Joana; Yamada, Fumio; Esteves, Pedro J

    2016-08-01

    Studies of the process of pseudogenization have widened our understanding of adaptive evolutionary change. In Rabbit, an alteration at the second extra-cellular loop of the CCR5 chemokine receptor was found to be associated with the pseudogenization of one of its prime ligands, the chemokine CCL8. This relationship has raised questions about the existence of a causal link between both events, which would imply adaptive gene loss. This hypothesis is evaluated here by tracing back the history of the genetic modifications underlying the chemokine pseudogenization. The obtained data indicate that mutations at receptor and ligand genes occurred after the lineage split of New World Leporids versus Old World Leporids and prior to the generic split of the of Old World species studied, which occurred an estimated 8-9 million years ago. More important, they revealed the emergence, before this zoographical split, of a "slippery" nucleotide motif (CCCCGGG) at the 3' region of CCL8-exon2. Such motives are liable of generating +1G or -1G frameshifts, which could, however, be overcome by "translesion" synthesis or somatic reversion. The CCL8 pseudogenization in the Old World lineage was apparently initiated by three synapomorphic point mutations at the exon2-intron2 boundary which provide at short range premature terminating codons, independently of the reading frame imposed by the slippery motif. The presence of this motif in New World Leporids might allow verifying this scenario. The importance of CCL8-CCR5 signaling in parasite-host interaction would suggest that the CCL8 knock-out in Old World populations might be related to changes in pathogenic environment. PMID:27306379

  16. Protective role of Juniperus phoenicea and Cupressus sempervirens against CCl4

    Institute of Scientific and Technical Information of China (English)

    Sanaa; Ahmed; Ali; Maha; Zaki; Rizk; Nabawia; Ali; Ibrahim; Mohga; Shafik; Abdallah; Hayat; Mohamed; Sharara; Magda; Mohamed; Moustafa

    2010-01-01

    AIM: To investigate the role of Cupressus sempervirens (C. sempervirens) and Juniperus phoenicea (J. phoe-nicea) extracts as therapeutic effect against CCl4 with biochemical, histopathological evaluations. METHODS: A single intraperitoneal dose of 10% CCl4 in olive oil (1 mL/kg body weight) was administered to a group of female Wister rats, sacrificed after 24 h (as the injury group). The other groups were given CCl4 as de-scribed above and divided as follows: two groups of ten rats each were orally administered either J. phoenicea extract or C. sempervirens extract three times per week for six weeks and a further group administered CCl4 was left for six weeks to allow self-recovery. At the end of experiment, the rats from all groups were sacrificed for sampling and for biochemical and histological analysis. RESULTS: Remarkable disturbances were observed in the levels of all tested parameters. On the other hand,rats injected with the toxic agent and left for one and a half month to self recover showed moderate improve-ments in the studied parameters while, treatment with both medicinal herbal extracts ameliorated the levels of the disturbed biochemical parameters. The group treated with J. phoenicea extract showed a remarkable improvement in comparison to the CCl4 treated group. The C. sempervirens group revealing an even more re-markable effect showing histopathological liver& kidney profiles close to those of the control group.CONCLUSION: C. sempervirens and J. phoenicea leaf extracts show a remarkable effect in enhancing liver and kidney functions and may thus be of therapeutic potential in treatment hepatotoxicity and nephrotoxicity.

  17. COPD promotes migration of A549 lung cancer cells: the role of chemokine CCL21

    Directory of Open Access Journals (Sweden)

    Kuźnar-Kamińska B

    2016-05-01

    Full Text Available Barbara Kuźnar-Kamińska,1 Justyna Mikuła-Pietrasik,2 Patrycja Sosińska,2 Krzysztof Książek,2 Halina Batura-Gabryel1 1Department of Pulmonology, Allergology and Respiratory Oncology, 2Department of Pathophysiology, Poznań University of Medical Sciences, Poznań, Poland Abstract: Patients with COPD develop lung cancer more frequently than healthy smokers. At the same time, molecular mediators promoting various aspects of cancer cell progression are still elusive. In this report, we examined whether COPD can be coupled with increased migration of non-small-cell lung cancer cells A549 and, if so, whether this effect may be related to altered production and activity of chemokines CCL21, CXCL5, and CXCL12. The study showed that the migration of A549 cells through the polycarbonate membrane and basement membrane extract toward a chemotactic gradient elicited by serum from patients with COPD was markedly higher as compared with serum from healthy donors. The concentration of CCL21 and CXCL12, but not CXCL5, in serum from patients with COPD was also increased. Experiments in which CCL21- and CXCL12-dependent signaling was blocked revealed that increased migration of the cancer cells upon treatment with serum from patients with COPD was mediated exclusively by CCL21. Collectively, our results indicate that COPD may contribute to the progression of lung cancer via CCL21-dependent intensification of cancer cell migration. Keywords: chemokines, COPD, lung cancer, migration

  18. Lateral fluid percussion injury of the brain induces CCL20 inflammatory chemokine expression in rats

    Directory of Open Access Journals (Sweden)

    Das Mahasweta

    2011-10-01

    Full Text Available Abstract Background Traumatic brain injury (TBI evokes a systemic immune response including leukocyte migration into the brain and release of pro-inflammatory cytokines; however, the mechanisms underlying TBI pathogenesis and protection are poorly understood. Due to the high incidence of head trauma in the sports field, battlefield and automobile accidents identification of the molecular signals involved in TBI progression is critical for the development of novel therapeutics. Methods In this report, we used a rat lateral fluid percussion impact (LFPI model of TBI to characterize neurodegeneration, apoptosis and alterations in pro-inflammatory mediators at two time points within the secondary injury phase. Brain histopathology was evaluated by fluoro-jade (FJ staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL assay, polymerase chain reaction (qRT PCR, enzyme linked immunosorbent assay (ELISA and immunohistochemistry were employed to evaluate the CCL20 gene expression in different tissues. Results Histological analysis of neurodegeneration by FJ staining showed mild injury in the cerebral cortex, hippocampus and thalamus. TUNEL staining confirmed the presence of apoptotic cells and CD11b+ microglia indicated initiation of an inflammatory reaction leading to secondary damage in these areas. Analysis of spleen mRNA by PCR microarray of an inflammation panel led to the identification of CCL20 as an important pro-inflammatory signal upregulated 24 h after TBI. Although, CCL20 expression was observed in spleen and thymus after 24h of TBI, it was not expressed in degenerating cortex or hippocampal neurons until 48 h after insult. Splenectomy partially but significantly decreased the CCL20 expression in brain tissues. Conclusion These results demonstrate that the systemic inflammatory reaction to TBI starts earlier than the local brain response and suggest that spleen- and/ or thymus-derived CCL20 might play a role in

  19. BMP15 Prevents Cumulus Cell Apoptosis Through CCL2 and FBN1 in Porcine Ovaries

    Directory of Open Access Journals (Sweden)

    Bo Zhai

    2013-07-01

    Full Text Available Background: Bone morphogenetic protein-15 (BMP15 is a maternal gene necessary for mammalian reproduction. BMP15 expression increased in oocytes accompanied by follicle growth and development. The function and regulation mechanism of BMP15 in porcine cumulus cell apoptosis process is still unclear now. Methods: In this study, flow cytometry (FCM was used to analyze the effects of BMP15 with different concentrations to cumulus cell apoptosis. High-throughput sequencing technology was carried out to screen regulatory genes linked closely with BMP15. In order to confirm the function of (MCP-1/CCL2 and FBN1 in cumulus cell apoptosis, RNA interference (RNAi method was used to inhibit the expression of (MCP-1/CCL2 and FBN1. Apoptosis and proliferation of cumulus cell treated with siRNA transfection technology were measured by FCM, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, quantitative real time-PCR (RT-qPCR and western blotting. Results: The results showed that the apoptosis levels of cumulus cell treated by BMP15 decreased significantly in a dose-dependent manner. The expression of related genes protein 1 (MCP-1/CCL2 and fibrillin1 (FBN1 were both regulated by BMP15. After transfection, the proliferation of porcine cumulus cells increased significantly and apoptosis of cumulus cells was prevented while FBN1 was silenced after BMP15 treatment. The proliferation of cumulus cells decreased significantly and apoptosis rate of cumulus cells increased significantly while CCL2 was silenced. Conclusion: The results obtained in this study firstly demonstrated that CCL2 and FBN1 are important regulatory factors of BMP15 in preventing cumulus cell apoptosis in porcine ovaries.

  20. Decorin prevents the development of CCl4-induced liver fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    Ma Rui; He Shilin; Liang Xiao; Yu Hong; Liang Yuelong; Cai Xiujun

    2014-01-01

    Background Liver fibrosis normally progresses to cirrhosis and destroys the normal architecture of the liver,resulting in liver dysfunction and irreversible cirrhosis.The aim of this study was to investigate the anti-fibrosis effect and the possible underlying mechanisms of decorin.Methods The mice model of liver fibrosis was induced by intraperitoneal injection of 50% (v/v) of carbon tetrachloride (CCl4) diluted in olive oil (1 ml/kg body weight) once every 2 days for 5 weeks.Three weeks after injecting CCl4 intraperitoneally,mice were randomly divided into normal control with vehicles only (olive oil),mouse model given CCl4 only,and CCl4 plus decorin (DCN,250 μg/kg).Two weeks later,all the mice were sacrificed and their liver tissues were analyzed for the expressions of genes related to liver fibrosis and under hematoxylin-eosin staining,Masson staining,and immunohistochemical staining of all groups.Aspartate transaminase,alanine transaminase,and total bilirubin of the serum were determined for evaluation of the liver function.Results Exogenous protein decorin could reduce liver fibrosis induced by CCl4 in mice.The degree of fibrosis in the experimental group was alleviated,and the contents of collagen fibers were lower in the experimental group than those of the control group.In addition,expressions of transforming growth factor β1 and α-smooth muscle actin decreased in the experimental group.Conclusions Taking liver fibrosis model of mouse as the experimental target and by injecting exogenous protein decorin into the model,we confirmed that decorin could inhibit the expression of proteins related to fibrosis and reduce the formation of liver fibrosis in mice.

  1. Diallyl disulfide inhibits TNFα induced CCL2 release through MAPK/ERK and NF-Kappa-B signaling.

    Science.gov (United States)

    Bauer, D; Redmon, N; Mazzio, E; Taka, E; Reuben, J S; Day, A; Sadrud-Din, S; Flores-Rozas, H; Soliman, K F A; Darling-Reed, S

    2015-09-01

    TNFα receptors are constitutively overexpressed in tumor cells, correlating to sustain elevated NFκB and monocyte chemotactic protein-1 (MCP-1/CCL2) expression. The elevation of CCL2 evokes aggressive forms of malignant tumors marked by tumor associated macrophage (TAM) recruitment, cell proliferation, invasion and angiogenesis. Previously, we have shown that the organo-sulfur compound diallyl disulfide (DADS) found in garlic (Allium sativum) attenuates TNFα induced CCL2 production in MDA-MB-231 cells. In the current study, we explored the signaling pathways responsible for DADS suppressive effect on TNFα mediated CCL2 release using PCR Arrays, RT-PCR and western blots. The data in this study show that TNFα initiates a rise in NFκB mRNA, which is not reversed by DADS. However, TNFα induced heightened expression of IKKε and phosphorylated ERK. The expression of these proteins corresponds to increased CCL2 release that can be attenuated by DADS. CCL2 induction by TNFα was also lessened by inhibitors of p38 (SB202190) and MEK (U0126) but not JNK (SP 600125), all of which were suppressed by DADS. In conclusion, the obtained results indicate that DADS down regulates TNFα invoked CCL2 production primarily through reduction of IKKε and phosphorylated-ERK, thereby impairing MAPK/ERK, and NFκB pathway signaling. Future research will be required to evaluate the effects of DADS on the function and expression of TNFα surface receptors. PMID:26100848

  2. Prevention of carbon tetrachloride (CCl4)-induced toxicity in testes of rats treated with Physalis peruviana L. fruit.

    Science.gov (United States)

    Abdel Moneim, Ahmed E

    2016-06-01

    Treatment of rats with carbon tetrachloride (CCl4; 2 ml/kg body weight) once a week for 12 weeks caused a significant decrease in serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone. These decreases in sex hormones were reduced with Physalis peruviana L. (Cape gooseberry) juice supplementation. In addition, testicular activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase suppressed with CCl4 were elevated after P. peruviana juice supplements. P. peruviana juice supplementation significantly increased the testicular glutathione and significantly decreased the level of lipid peroxidation and the nitric oxide production compared with the CCl4 group. In addition, the decline in the activity of antioxidant enzymes after CCl4 was ameliorated by P. peruviana Moreover, degeneration of germ and Leydig cells along with deformities in spermatogenesis induced after CCl4 injections were prevented with the supplementation of P. peruviana juice. Furthermore, P. peruviana juice attenuated CCl4-induced apoptosis in testes tissue by inhibition of caspase-3 activity. The results clearly demonstrate that P. peruviana juice augments the antioxidants defense mechanism against CCl4-induced reproductive toxicity and provides evidence that the juice may have a therapeutic role in free radical-mediated diseases and infertility. PMID:25147302

  3. Bovine CCL28 Mediates Chemotaxis via CCR10 and Demonstrates Direct Antimicrobial Activity against Mastitis Causing Bacteria.

    Directory of Open Access Journals (Sweden)

    Kyler B Pallister

    Full Text Available In addition to the well characterized function of chemokines in mediating the homing and accumulation of leukocytes to tissues, some chemokines also exhibit potent antimicrobial activity. Little is known of the potential role of chemokines in bovine mammary gland health and disease. The chemokine CCL28 has previously been shown to play a key role in the homing and accumulation of IgA antibody secreting cells to the lactating murine mammary gland. CCL28 has also been shown to act as an antimicrobial peptide with activity demonstrated against a wide range of pathogens including bacteria, fungi and protozoans. Here we describe the cloning and function of bovine CCL28 and document the concentration of this chemokine in bovine milk. Bovine CCL28 was shown to mediate cellular chemotaxis via the CCR10 chemokine receptor and exhibited antimicrobial activity against a variety of bovine mastitis causing organisms. The concentration of bovine CCL28 in milk was found to be highly correlated with the lactation cycle. Highest concentrations of CCL28 were observed soon after parturition, with levels decreasing over time. These results suggest a potential role for CCL28 in the prevention/resolution of bovine mastitis.

  4. Dose dependent effects of platelet derived chondroitinsulfate A on the binding of CCL5 to endothelial cells

    Directory of Open Access Journals (Sweden)

    Krämer Bernhard K

    2008-12-01

    Full Text Available Abstract Background Chemokines immobilized on endothelial cells play a central role in the induced firm adhesion and transendothelial migration of leukocytes. Activation of platelets at sites of vascular injury is considered to support leukocyte adhesion and extravasation. However, activated platelets also secrete soluble glycosaminoglycans that can interfere with immobilization of chemokines. We therefore analyzed the impact of platelet derived glycosaminoglycans on the immobilization of the chemokine CCL5 (RANTES on human microvascular endothelial cells and their influence on CCL5-CCR5 interactions. Results We confirm that undiluted serum in contrast to plasma decreases binding of CCL5 to endothelial cells. However, when lower concentrations of serum were used, CCL5-presentation on endothelial cells was markedly enhanced. This enhancement was neutralized if serum was digested with chondroinitase ABC. Using different chondroitinsulfate-subtypes we demonstrate that chondroitinsulfate A mediates the enhanced presentation of CCL5 on endothelial cells, whereas chondroitinsulfate B/C even at low concentrations block CCL5 binding. CCR5 downregulation on CCR5-transfected CHO cells or human monocytes is increased by preincubation of CCL5 with serum or chondroitinsulfate A. Conclusion We show that chondroitinsulfate A released from platelets increases the binding of chemokines to endothelial cells and supports receptor internalization in a dose dependent manner. These data help to understand the proinflammatory effects of activated platelets.

  5. CCL5 promotes proliferation of MCF-7 cells through mTOR-dependent mRNA translation

    Energy Technology Data Exchange (ETDEWEB)

    Murooka, Thomas T.; Rahbar, Ramtin [Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, Ont. (Canada); Department of Immunology, University of Toronto, Ont. (Canada); Fish, Eleanor N., E-mail: en.fish@utoronto.ca [Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, Ont. (Canada); Department of Immunology, University of Toronto, Ont. (Canada)

    2009-09-18

    The proliferative capacity of cancer cells is regulated by factors intrinsic to cancer cells and by secreted factors in the microenvironment. Here, we investigated the proto-oncogenic potential of the chemokine receptor, CCR5, in MCF-7 breast cancer cell lines. At physiological levels, CCL5, a ligand for CCR5, enhanced MCF-7.CCR5 proliferation. Treatment with the mTOR inhibitor, rapamycin, inhibited this CCL5-inducible proliferation. Because mTOR directly modulates mRNA translation, we investigated whether CCL5 activation of CCR5 leads to increased translation. CCL5 induced the formation of the eIF4F translation initiation complex through an mTOR-dependent process. Indeed, CCL5 initiated mRNA translation, shown by an increase in high-molecular-weight polysomes. Specifically, we show that CCL5 mediated a rapid up-regulation of protein expression for cyclin D1, c-Myc and Dad-1, without affecting their mRNA levels. Taken together, we describe a mechanism by which CCL5 influences translation of rapamycin-sensitive mRNAs, thereby providing CCR5-positive breast cancer cells with a proliferative advantage.

  6. CCl4对左旋氧氟沙星超声降解的影响%Effect of CCl4 on Antibiotics Levofloxacin' s Ultrasonic Degradation

    Institute of Scientific and Technical Information of China (English)

    魏红; 李娟; 李克斌; 孙剑宇; 赵锋

    2012-01-01

    The ultrasonic degradation of quinolone antibiotics levofloxacin in water with CC14 enhancement was investigated. The effects of CC14.dosage, ultrasonic power, pH value and initial concentration of levofloxacin were discussed. The products were examined by HPLC and LC-MS/MS. The results.indicated that the ultrasonic degradation of levofloxacin was obviously enhanced by CC14 addition; the degradation efficiency increased from 1. 9% to 69. 2% with CC14 dosage changed from 0 to 0. 06% ( volume fraction). The enhancement effect was attributed to the increasing · OH radical concentration and formation of chlorine-containing radicals in the presence of CC14 during ultrasonic processes. Levofloxacin degradation efficiency by ultrasonic in the presence of CC14 increased with the increasing of ultrasonic power in 100-200 W. The pH values of solution had prominent effect on levofloxacin degradation, while the initial concentration of levofloxacin had a negative effect. The temperature between 33-49 ℃ was found to be favorable to levofloxacin degradation. Moreover, HPLC analysis showed that two main by-products were simultaneously produced in the course of the ultrasonic degradation of levofloxacin in addition of CC14, the two products were confirmed by LC-MS/MS analysis.%研究了CCl4对超声降解喹诺酮类抗生素左旋氧氟沙星(Levofloxacin)的影响,考察了CCl4添加量、超声功率、溶液初始pH值及左旋氧氟沙星初始浓度等影响因素,并采用HPLC和LC-MS/MS对超声降解产物进行了初步分析.结果表明,CCl4增强了左旋氧氟沙星的超声降解,当反应液体积为50 mL,超声35 min时,随着CCl4体积分数的增大(0~0.06%),左旋氧氟沙星的降解率由1.9%增至69.2%;超声功率为100 ~200 W时,降解率随着功率的升高而增大,功率为200~400 W时降解率有所降低;pH值对左旋氧氟沙星的超声降解影响很大,pH =7.14时容易超声降解,pH过低或过高均导致降解率显著减小;CCl

  7. HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

    Energy Technology Data Exchange (ETDEWEB)

    Al-Haidari, Amr A.; Syk, Ingvar; Thorlacius, Henrik, E-mail: henrik.thorlacius@med.lu.se

    2014-03-28

    Highlights: • Simvastatin blocked CCL17-induced and CCR4-dependent RhoA activation in HT29 cells. • CCL17/CCR4-mediated migration of colon cancer cells was antagonised by simvastatin. • Cell migration recovered by adding Mevalonate and geranylgeranyl pyrophosphate. • Targeting HMG-CoA reductase might be useful to inhibit colon cancer metastasis. - Abstract: Background: Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects. Aim: The aim of this study was to examine the effect of simvastatin on colon cancer cell migration. Methods: Migration assays were performed to evaluate CCL17-induced colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were assessed using a proliferation assay and annexin V assay, respectively. Active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using a G-LISA assay. Results: We found that simvastatin dose-dependently decreased CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4, CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover, administration of mevalonate reversed the inhibitory effect of simvastatin on CCL17-induced colon cancer cell migration. Interestingly, co-incubation with geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells. Conclusions: Taken together, our findings show for the first time that HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via

  8. Structural and functional characterization of the interactions of platelet derived chemokines CCL5, CXCL4 and CXCL4L1

    OpenAIRE

    Sarabi, Alisina

    2011-01-01

    Chemokines play an important role in the development of inflammation and in the recruitment of leukocytes from the vessel into the inflamed tissue. Activated platelets serve as a rich source of chemokines, e.g. CCL5, CXCL4 and its closely related variant CXCL4L1. The pro-inflammatory CCL5 is a known potent chemoattractant for monocytes and also responsible for its arrest on inflamed endothelium. Since this arrest is enhanced by the interaction of CCL5 with CXCL4, we aimed to determine the str...

  9. Protective effect of recombinant human IL-1Ra on CCl_4-induced acute liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl 4 ). METHODS: Acute liver damage was induced by injecting 8-wk-old mice with CCl 4 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl 4 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneo...

  10. Chicory (Cichorium intybus L.) Root Extract Regulates the Oxidative Status and Antioxidant Gene Transcripts in CCl4-Induced Hepatotoxicity

    OpenAIRE

    El-Sayed, Yasser S.; Lebda, Mohamed A.; Mohammed Hassinin; Neoman, Saad A.

    2015-01-01

    The ability of Cichorium intybus root extract (chicory extract) to protect against carbon tetrachloride (CCl4)-induced oxidative stress and hepatotoxicity was evaluated in male rats. The rats were divided into four groups according to treatment: saline (control); chicory extract (100 mg/kg body weight daily, given orally for 2 weeks); CCl4 (1 ml/kg body weight by intraperitoneal injection for 2 consecutive days only); or chicory extract (100 mg/kg body weight daily for 2 weeks) + CCl4 injecti...

  11. HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

    International Nuclear Information System (INIS)

    Highlights: • Simvastatin blocked CCL17-induced and CCR4-dependent RhoA activation in HT29 cells. • CCL17/CCR4-mediated migration of colon cancer cells was antagonised by simvastatin. • Cell migration recovered by adding Mevalonate and geranylgeranyl pyrophosphate. • Targeting HMG-CoA reductase might be useful to inhibit colon cancer metastasis. - Abstract: Background: Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects. Aim: The aim of this study was to examine the effect of simvastatin on colon cancer cell migration. Methods: Migration assays were performed to evaluate CCL17-induced colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were assessed using a proliferation assay and annexin V assay, respectively. Active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using a G-LISA assay. Results: We found that simvastatin dose-dependently decreased CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4, CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover, administration of mevalonate reversed the inhibitory effect of simvastatin on CCL17-induced colon cancer cell migration. Interestingly, co-incubation with geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells. Conclusions: Taken together, our findings show for the first time that HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via

  12. P1/Fas-CCL19双表达重组腺病毒载体的构建及表达鉴定%Construction and Identification of PI/Fas-CCL19 Double Expressed Reorganization Adenovirus Carrier

    Institute of Scientific and Technical Information of China (English)

    姜兆静; 李纪强; 张积仁

    2012-01-01

    目的 利用pAdEasy-1腺病毒包装系统构建血型B抗原模拟多肽P1/Fas CCL19双表达重组腺病毒,并在体内外试验中验证其表达及可能的疗效.方法 应用腺病毒穿梭质粒pShuttle-CMV、骨架质粒pAdEasy-1构建重组腺病毒质粒pAd-CMV-P1/Fas-CCL19并转染至HEK293A细胞,获得重组腺病毒Ad-P1/Fas-CCL19颗粒后进一步感染乳腺癌4T1细胞并鉴定转染4T1细胞内P1/Fas-CCL19mRNA和蛋白质的表达.构建经人B型血红细胞免疫的4T1荷瘤小鼠模型,比较瘤内注射重组腺病毒Ad-P1/Fas-CCL19组、空腺病毒组、0.9%氯化钠溶液组的荷瘤小鼠的肿瘤变化及生存期.结果 感染后4T1细胞中P1/Fas-CCL19 mRNA和蛋白质均有表达.瘤内注射重组腺病毒Ad-P1/Fas-CCL19较瘤内注射空腺病毒、0.9%氯化钠溶液明显抑制4T1肿瘤的生长,但三组小鼠的生存期无明显区别.结论 P1/Fas-CCL19重组腺病毒载体成功构建,体内外实验均证明了其稳定表达及有效性,为进一步临床研究奠定了基础.%Objective To construct recombinant adenovirus expressing both simulated peptide of blood group B antigen Pi/Fas and CCL19 by pAdEasy-1 packaging system,and test their expression. Methods We constructed pShutt Ie-CMV-P1/Fas-CCL19 by adenovirus Shuttle plasmid pShuttle-CMV and pAdEasy-1. Then,we transfected pAd-CMV-P1/Fas CCL19 to HEK293A cells and obtained recombinant Ad-Pl/Fas-CCL19 particles which can infect 4T1 cells. At last we detected mRNA and protein expression of Pl/Fas-CCL19 in 4T1 cells. 4T1 tumor-bearing mice model immuned by the B red blood cell was established successfully,and injected with recombinant adenovirus Ad-Pl/Fas-CCL19,empty adenovirus,saline into the tumors, respectively. Then, tumor changes and survival period of the three groups were compared. Results Pl/Fas-CCL19 can be effectively expressed in 4T1 cells on both mRNA and protein levels. Intratumor injection of recombinant adenovirus Ad-Pl/Fas-CCL19 group inhibited 4T1

  13. Reaction of carotenoids with CCl3OO· by using pulse radiolysis

    Institute of Scientific and Technical Information of China (English)

    赵文恩; 姚思德; 王强; 钱素平; 王文峰; 韩雅珊

    2003-01-01

    The interactions of carotenoids (bixin, β-carotene and lycopene) with CCl3OO@ in aqueous and i-propylalcohol solution saturated with air have been studied by pulse radiolysis. For bixin and β-carotene reaction products from forming process, absorbing in the region of 650 nm, is observed with concomitant carotenoid bleaching (bixin at 500 nm, β-carotene at 450 nm). Their rate constants from forming process are 1.78×108 and 7.8×107 mol-1@L@s-1 respectively. However, in the case of lycopene, no such a forming process of reaction as bixin and β-carotene can be observed although there is the bleaching reaction (rate constant 4×107 mol-1@L@s-1). The results suggest that the carotenoid radical cationand an additional radical are produced in the case of bixin and β-carotene, whereas lycopene undergoes electron transfer with CCl3OO@, forming cation radical.

  14. Antihepatotoxic effect of golden berry (Physalis peruviana Linn.) in carbon tetrachloride (CCl4) intoxicated rats.

    Science.gov (United States)

    Taj, Darakhshan; Khan, Hira; Sultana, Viqar; Ara, Jehan; Ehteshamul-Haque, Syed

    2014-05-01

    Liver is the main site in the body for intense metabolism and excretion. A number of chemicals and drugs which are used routinely cause liver damage. The present study investigates the antihepatotoxic effect of Physalis peruviana whole ripe fruit, water and ethanol extracts of fruit in normal as well as in carbon tetrachloride (CCl(4)) intoxicated rats. The CCl(4) treated rats showed marked elevation in liver enzymes: alanine transaminse, aspratate transaminase, alkaline phosphatase, lactate dehydrogenase and other biochemical parameters: bilirubin, creatinine and urea, thus indicating liver injury. Whereas animal treated/fed with various preparations of Physalis peruviana showed significant lowering effect (pPhysalis peruviana showed highest activity in both rat models while ripe fruit and ethanol extract showed moderate activity compared to standard drug. PMID:24811807

  15. Suppression of intratumoral CCL22 by type i interferon inhibits migration of regulatory T cells and blocks cancer progression.

    Science.gov (United States)

    Anz, David; Rapp, Moritz; Eiber, Stephan; Koelzer, Viktor H; Thaler, Raffael; Haubner, Sascha; Knott, Max; Nagel, Sarah; Golic, Michaela; Wiedemann, Gabriela M; Bauernfeind, Franz; Wurzenberger, Cornelia; Hornung, Veit; Scholz, Christoph; Mayr, Doris; Rothenfusser, Simon; Endres, Stefan; Bourquin, Carole

    2015-11-01

    The chemokine CCL22 is abundantly expressed in many types of cancer and is instrumental for intratumoral recruitment of regulatory T cells (Treg), an important subset of immunosuppressive and tumor-promoting lymphocytes. In this study, we offer evidence for a generalized strategy to blunt Treg activity that can limit immune escape and promote tumor rejection. Activation of innate immunity with Toll-like receptor (TLR) or RIG-I-like receptor (RLR) ligands prevented accumulation of Treg in tumors by blocking their immigration. Mechanistic investigations indicated that Treg blockade was a consequence of reduced intratumoral CCL22 levels caused by type I IFN. Notably, stable expression of CCL22 abrogated the antitumor effects of treatment with RLR or TLR ligands. Taken together, our findings argue that type I IFN blocks the Treg-attracting chemokine CCL22 and thus helps limit the recruitment of Treg to tumors, a finding with implications for cancer immunotherapy. PMID:26432403

  16. Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice

    OpenAIRE

    Zhu, Run-Zhi; Xiang, Di; Xie, Chao; Li, Jing-Jing; Hu, Jian-Jun; He, Hong-Lin; Yuan, Yun-Sheng; GAO, JIN; HAN, WEI; Yu, Yan

    2010-01-01

    AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl4).

  17. Expression and histopathological correlation of CCR9 and CCL25 in ovarian cancer

    OpenAIRE

    Singh, Rajesh; Cecil R. Stockard; Grizzle, William E.; Lillard, James W.; Singh, Shailesh

    2011-01-01

    Ovarian carcinoma is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells. The interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for ovarian cancer cells. We have previously shown that ovarian cancer cells express CCR9 and play an important role in cell migration, invasion and surviva...

  18. CCL2-ethanol interactions and hippocampal synaptic protein expression in a transgenic mouse model

    OpenAIRE

    Gruol, Donna L.; Vo, Khanh; Bray, Jennifer G.; Roberts, Amanda J.

    2014-01-01

    Chronic exposure to ethanol produces a number of detrimental effects on behavior. Neuroadaptive changes in brain structure or function underlie these behavioral effects and may be transient or persistent in nature. Central to the functional changes are alterations in the biology of neuronal and glial cells of the brain. Recent data show that ethanol induces glial cells of the brain to produce elevated levels of neuroimmune factors including CCL2, a key innate immune chemokine. Depending on th...

  19. Pharmacological investigation of Polyherbal formulation on Carbon tetrachloride (CCl4-induced liver damage in wistar rats

    Directory of Open Access Journals (Sweden)

    Hardik Soni

    2014-09-01

    Full Text Available Objective: To investigate effect of Polyherbal formulation on Carbon tetrachloride (CCl4-induced liver damage in wistar rats. Methods: Wistar albino rats weighing 180-230 g either sex were used. The selected animals were divided in to four groups where each group consisted of six animals. Experimentally liver damage was produced by intra-peritoneal administration of CCl4 and olive oil mixture (1:1 v/v (1 mL/kg, once daily, i.p. for 7 days. Test Drug, Polyherbal formulation was administered orally for 7 consecutive days at 3 mL/kg, once daily. On 8th day, Blood samples were collected to evaluate different serum biochemical parameters like Aspartate aminotransferase (AST, Alanine aminotransferase (ALT, Alkaline phosphatase (ALP, Total bilirubin and Total protein. Liver from animals of each group was dissected out for histopathological examination. Statistical analysis: Statistical calculation were done by analysis of variance (ANOVA followed by post hoc Dunnett’s test, with significant level of p<0.05. Results and dDiscussion: Polyherbal formulation showed significant effect on activity levels of serum AST, ALT, ALP and total bilirubin level while comparing test group to disease control group. It also showed significant elevation in decreased level of serum total protein. Pre-treatment of Polyherbal formulation restored the hepatic architecture and protected the liver tissue from fatty degenerative changes by preventing the toxic chemical reaction induced by CCl4. Conclusion: Finding of this study concludes that Polyherbal formulation (Vasuliv Syrup has promising hepatoprotective activity against CCl4-induced liver damage. It can be employed as safe and effective treatment for hepato-toxicity or liver damage.

  20. Hepatoprotective effects of baicalein against CCl4-induced acute liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    Hai-Li Huang; Ya-Jing Wang; Qing-Yu Zhang; Bin Liu; Fang-Yuan Wang; Jing-Jing Li; Run-Zhi Zhu

    2012-01-01

    AIM:To investigate the hepatoprotective effect of baicalein against carbon tetrachloride (CCl4)-induced liver damage in mice.METHODS:Mice were orally administered with baicalein after CCl4 injection,and therapeutic baicalein was given twice a day for 4 d.The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement.Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation.Serum interleukin (IL)-6,IL-1β and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay and liverIL-6,TNF-α,transforming growth factor-α (TGF-α),hepatocyte growth factor (HGF) and epidermal growth factor (EGF) genes expression were determined by quantitative real-time polymerase chain reaction.RESULTS:CCl4-induced acute liver failure model offers a survival benefit in baicalein-treated mice.The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl4 treatment in baicalein administration groups,but at 24,48 and 72h,the expression of IL-6 and TNF-α was kept at lower levels compared with the control.The expression of TGF-α,HGF and EGF was enhanced dramatically in baicalein administration group at 12,24,48 and 72 h.Furthermore,we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase,which indicated that baicalein could facilitate the initiating events in liver regeneration.CONCLUSION:Baicalein may be a therapeutic candidate for acute liver injury.Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.

  1. PROTECTIVE ABILITY OF MOMORDICA CHARANTIA L AGAINST CCL4 INDUCED HEPATIC DAMAGE IN RATS

    OpenAIRE

    Pingale Shirish S

    2010-01-01

    The aim of this study is to evaluate the efficacy of Momordica charantia on the experimental hepatotoxicity induced by carbon tetrachloride (CCl4). Carbon tetrachloride was administered once and simultaneously suspension of dry fruit powder was prepared in aqueous medium and was daily administered at a dose level of 1mg/kg body weight for 4 days. Silymarin was used as a standard drug for this study. Administration of carbon tetrachloride showed significant changes in the levels of serum amino...

  2. HEPATOPROTECTIVE EFFECT OF METHANOLIC EXTRACT OF HEDYOTIS HERBACEA LINN IN CCl4 TREATED MALE RATS

    OpenAIRE

    Sharma Naveen; Jain AK; Sharma Vipin; Jain Suman; Saluja Gurdeep

    2012-01-01

    To evaluate the hepatoprotective effect of methanolic extract of Hedyotis herbacea Linn in rats treated with CCl4. In Hepatotoxic rats, liver damage was studied by assessing parameters such as aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphate transferase (ALP) and gamma glutamyl transpeptidase (GGT) in serum and concentration of total proteins, total lipids, phospholipids, triglycerides and cholesterol in both serum and liver. The effect of co-administrati...

  3. CCL2 is transcriptionally controlled by the lysosomal protease cathepsin S in a CD74-dependent manner

    OpenAIRE

    Wilkinson, Richard; Magorrian, Sinead; Williams, Richard; Young, Andrew; Small, Donna; Scott, Christopher; Burden, Roberta

    2015-01-01

    Cathepsins S (CatS) has been implicated in numerous tumourigenic processes and here we document for the first time its involvement in CCL2 regulation within the tumour microenvironment. Analysis of syngeneic tumours highlighted reduced infiltrating macrophages in CatS depleted tumours. Interrogation of tumours and serum revealed genetic ablation of CatS leads to the depletion of several pro-inflammatory chemokines, most notably, CCL2. This observation was validated in vitro, where shRNA deple...

  4. The Protective Effect of Liquorice Plant Extract on CCl4-Induced Hepatotoxicity in Common Carp (Cyprinus carpio

    Directory of Open Access Journals (Sweden)

    Hassan Malekinejad

    2010-12-01

    Full Text Available The protective effect of liquorice plant extract (LPE on CCl4-induced hepatotoxicity in common carp was evaluated using fifty adult carps. The fish were cultured in a standard environment in terms of water flow rate, oxygen, pH, food and temperature. The fish were assigned into 5 groups (N = 10 as control, sham, and tests. The test groups were pre-treated for 3 h with various concentrations of LPE, 3 days before CCl4 exposure. The control and sham groups received normal saline before and after CCl4 exposure. To induce hepatotoxicity, animals in the sham and test groups were exposed against 100 l L-1 CCl4 for 45 min. The fish in all groups 1 h after CCl4 exposure were anesthetized and the blood samples were collected. Immediately the liver specimens were dissected out and were stored in 10 % formalin for further pathological studies. Determination of serum level of ALP and SGOT revealed that acute form of CCl4 exposure elevated significantly (P < 0.05 the serum level of either tested hepatic marker enzymes. While 3 days pretreatment with LPE prevented from ALP and SGOT enhancement. The pathological evaluation revealed that the CCl4 exposure resulted in a minor pathologic manifestation such as slight congestion, which the LPE pretreated groups showed the remarkable improvement. The anti-oxidant capacity of LPE was assayed by FRAP and DPPH methods. Both provided techniques showed that LPE exerts an excellent anti-oxidant effect. This data suggest that LPE exerts protective effect against CCl4-induced hepatotoxicity. Moreover, the hepatoprotective effect of LPE may attribute to its antioxidant capacity.

  5. Curcumin or saikosaponin a improves hepatic antioxidant capacity and protects against CCl4-induced liver injury in rats.

    Science.gov (United States)

    Wu, Shu-Ju; Lin, Yun-Ho; Chu, Chia-Chou; Tsai, Ya-Hui; Chao, Jane C-J

    2008-06-01

    Curcumin and saikosaponin a, the bioactive phytochemicals of turmeric and Bupleurum, act as antioxidants. This study investigated the effects of supplementation with curcumin and/or saikosaponin a on hepatic lipids and antioxidant status in rats with CCl(4)-induced liver injury. Male Sprague-Dawley rats were randomly divided into control, CCl(4), CCl(4) + curcumin (0.005%; CU), CCl(4) + saikosaponin a (0.004%; SS), and CCl(4) + curcumin + saikosaponin a (0.005% + 0.004%; CU+SS) groups. CCl(4) (40% in olive oil) was injected intraperitoneally at a dose of 0.75 mL/kg once a week. Curcumin and/or saikosaponin a was administered orally 1 week before CCl(4) injection for 8 weeks. The pathological results showed that liver fibrosis was ameliorated in the SS and CU+SS groups. After 8 weeks, supplementation with curcumin and/or saikosaponin a significantly decreased plasma alanine aminotransferase and aspartate aminotransferase activities, as well as plasma and hepatic cholesterol and triglyceride levels. The CU+SS group showed reversal of the impaired hepatic superoxide dismutase activity and an increase in total glutathione level. Supplementation with curcumin and/or saikosaponin a significantly improved hepatic antioxidant status and suppressed malondialdehyde formation. Therefore, supplementation with curcumin and/or saikosaponin a protects against CCl(4)-induced liver injury by attenuating hepatic lipids and lipid peroxidation and enhancing antioxidant defense. Curcumin and saikosaponin a had no additive effects on hepatoprotection except for greater improvement in the total glutathione level and antioxidant status.

  6. Structures of Trichloromethyl Thiocyanate, CCl3 SCN, in Gaseous and Crystalline State.

    Science.gov (United States)

    Berrueta Martínez, Yanina; Rodríguez Pirani, Lucas S; Erben, Mauricio F; Boese, Roland; Reuter, Christian G; Vishnevskiy, Yury V; Mitzel, Norbert W; Della Védova, Carlos O

    2016-05-18

    Trichloromethyl thiocyanate, CCl3 SCN, was structurally studied in both the gas and crystal phases by means of gas electron diffraction (GED) and single-crystal X-ray diffraction (XRD), respectively. Both experimental studies and quantum chemical calculations indicate a staggered orientation of the CCl3 group relative to the SCN group. This conclusion is supported by the similarity of the C-SCN bond length to that of the anti-structure of CH2 ClSCN (Berrueta Martínez et al. Phys. Chem. Chem. Phys. 2015, 17, 15805-15812). Bond lengths and angles are similar for gas and crystal CCl3 SCN structures; however, the crystal structure presents different intermolecular interactions. These include halogen and chalcogen type interactions, the geometry of which was studied. Characteristic C-Y⋅⋅⋅N angles (Y=Cl or S) close to 180° provide evidence for typical σ-hole interactions along the halogen/chalcogen-carbon bond in N⋅⋅⋅Cl and N⋅⋅⋅S, intermolecular units. PMID:26865044

  7. [Triterpenoids from Inonotus obliquus protect mice against oxidative damage induced by CCl4].

    Science.gov (United States)

    Zhao, Fen-Qin; Yan, Lin; Cui, Xian-Hong; Lin, Sheng; Wang, Cong; Zhang, Hui; Kang, Xiao-Yan; Ji, Bian-Sheng

    2012-05-01

    To investigate the effects of lanosterol (1), inotodiol (2) and trametenolic acid (3) from Inonotus obliquus against oxidative damage induced by CCl4 in mice, 1, 2 and 3 (20, 10 and 5 mg x kg(-1)) were respectively administered to mice, once a day for 3 days. Then the mice were induced to oxidative damage by CCl4 on the third day 30 min after the administration. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and the content of malondialdehyde (MDA) and reductive glutathione (GSH) in serum and liver homogenate were determined. And the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and interleukin-6 (IL-6) concentration in serum were detected. The results showed that treatment with compound 1, 2 and 3 could significantly increase the activities of SOD, CAT and GSH-PX in serum and liver homogenate. Furthermore, the content of GSH in serum and liver homogenate increased and MDA content decreased markedly. In addition, compound 1, 2 and 3 could significantly inhibit the activities of ALT and AST in serum, and decrease the IL-6 concentration in serum remarkably. So, compound 1, 2 and 3 can protect mice against oxidative stress injury induced by CCl4. Furthermore, compound 1, 2 and 3 can protect cells from damage through inhibition on ALT, AST and the expression of IL-6. PMID:22812017

  8. The protective effect of ENA Actimineral resource A on CCl4-induced liver injury in rats.

    Science.gov (United States)

    Hong, Il-Hwa; Ji, Hoon; Hwa, Sung-Yong; Jeong, Won-Il; Jeong, Da-Hee; Do, Sun-Hee; Kim, Ji-Min; Ki, Mi-Ran; Park, Jin-Kyu; Goo, Moon-Jung; Hwang, Ok-Kyung; Hong, Kyung-Sook; Han, Jung-Youn; Chung, Hae-Young; Jeong, Kyu-Shik

    2011-06-01

    ENA Actimineral Resource A (ENA-A) is alkaline water that is composed of refined edible cuttlefish bone and two different species of seaweed, Phymatolithon calcareum and Lithothamnion corallioides. In the present study, ENA-A was investigated as an antioxidant to protect against CCl(4)-induced oxidative stress and hepatotoxicity in rats. Liver injury was induced by either subacute or chronic CCl(4) administration, and the rats had free access to tap water mixed with 0% (control group) or 10% (v/v) ENA-A for 5 or 8 weeks. The results of histological examination and measurement of antioxidant activity showed that the reactive oxygen species production, lipid peroxidation, induction of CYP2E1 were decreased and the antioxidant activity, including glutathione and catalase production, was increased in the ENA-A groups as compared with the control group. On 2-DE gel analysis of the proteomes, 13 differentially expressed proteins were obtained in the ENA-A groups as compared with the control group. Antioxidant proteins, including glutathione S-transferase, kelch-like ECH-associated protein 1, and peroxiredoxin 1, were increased with hepatocyte nuclear factor 3-beta and serum albumin precursor, and kininogen precursor decreased more in the ENA-A groups than compared to the control group. In conclusion, our results suggest that ENA-A does indeed have some protective capabilities against CCl(4)-induced liver injury through its antioxidant function.

  9. Protective effect of Sida cordata leaf extract against CCl4 induced acute liver toxicity in rats

    Institute of Scientific and Technical Information of China (English)

    Sunil Mistry; KR Dutt; J Jena

    2013-01-01

    Objective: To investigate the hepatoprotective potential of Sida cordata (Malvaceae) (S. cordata) in experimental rats to validate its traditional claim. Methods: Wister albino rats were divided into 6 groups: Group Ⅰ served as control; Group Ⅱ served as hepatotoxic (CCl4 treated) group;Group Ⅲ, Ⅳ and Ⅴ served as (100, 200 and 400 mg/kg b.w.) S. cordata leaf extract (SCLE) treated groups; Group Ⅵ served as positive control (Silymarin) treated group. Liver marker enzymes serum glutamate oxyloacetic transaminase, serum glutamic pyruvic transaminase, pancreatic enzymatic antioxidants superoxide dismutase (SOD), lipid peroxidation, catalase (CAT), reduced glutathione (GSH) were measured and compared along with histopathological studies. Results:Obtained results show that the treatment with SCLE significantly (P<0.05-<0.001) and dose-dependently reduced CCl4 induced elevated serum level of hepatic enzymes. Furthermore, SCLE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels, which was confirmed by the histopathological studies. Conclusions: The results of this study strongly indicate the protective effect of SCLE against CCl4 induced acute liver toxicity in rats and thereby scientifically support its traditional use.

  10. C-terminal engineering of CXCL12 and CCL5 chemokines: functional characterization by electrophysiological recordings.

    Directory of Open Access Journals (Sweden)

    Antoine Picciocchi

    Full Text Available Chemokines are chemotactic cytokines comprised of 70-100 amino acids. The chemokines CXCL12 and CCL5 are the endogenous ligands of the CXCR4 and CCR5 G protein-coupled receptors that are also HIV co-receptors. Biochemical, structural and functional studies of receptors are ligand-consuming and the cost of commercial chemokines hinders their use in such studies. Here, we describe methods for the expression, refolding, purification, and functional characterization of CXCL12 and CCL5 constructs incorporating C-terminal epitope tags. The model tags used were hexahistidines and Strep-Tag for affinity purification, and the double lanthanoid binding tag for fluorescence imaging and crystal structure resolution. The ability of modified and purified chemokines to bind and activate CXCR4 and CCR5 receptors was tested in Xenopus oocytes expressing the receptors, together with a Kir3 G-protein activated K(+ channel that served as a reporter of receptor activation. Results demonstrate that tags greatly influence the biochemical properties of the recombinant chemokines. Besides, despite the absence of any evidence for CXCL12 or CCL5 C-terminus involvement in receptor binding and activation, we demonstrated unpredictable effects of tag insertion on the ligand apparent affinity and efficacy or on the ligand dissociation. These tagged chemokines should constitute useful tools for the selective purification of properly-folded chemokines receptors and the study of their native quaternary structures.

  11. Design and Analysis of Vacuum Pumping Systems for SNS DTL and CCL Linac

    Energy Technology Data Exchange (ETDEWEB)

    Shen, S; Tung, L; Kishiyama, K; Nederbragt, W; Bernardin,; Bustos, G; Gillis, R; Meyer, Sr, R

    2001-06-14

    The mechanical design of the vacuum pumping systems for SNS DTL (Drift Tube Linac) and CCL (Cavity Coupled Linac) linac systems is summarized. Both vacuum systems were modeled to select the optimal pump configuration. The pressure history in up to 182 sub-volumes was analyzed in detail. Included in the model are time-dependent outgassing rates and pressure-dependent pump speeds for a variety of gas species. With this information, we solved for the pressure history during roughing and with turbo and ion pumps. The number and size of each pump were optimized to achieve the desired pressure with minimal costs. In the optimized design, directly mounted ion pumps were provided for six DTL tanks. For four CCL modules (each in length of 12-15 m), ion pumps with manifolds were selected. With all metallic surface outgassing, seal leakage and expected gas loads from all diagnostic devices taken into account, the designed systems can provide operating drift-tube pressure below 1.8 x 10{sup -7} Torr and CCL beamline pressures below 9.2 x 10{sup -8} Torr even under abnormal conditions. Details of the design and the modeling results are presented.

  12. Ginkgo biloba extract reverses CCl4-induced liver fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    Yan-Jun Luo; Jie-Ping Yu; Zhao-Hong Shi; Li Wang

    2004-01-01

    AIM: To study the reversing effect of Ginkgo biloba extract (GbE) on established liver fibrosis in rats.METHODS: Following confirmation of CCl4-induced liver fibrosis, GbE or saline was administrated to the rats for 4 weeks. The remaining rats received neither CCl4 nor GbE as normal control. The four groups were compared in terms of serum enzymes, tissue damage, expression of αSMA and tissue inhibitor-1 of metalloproteinase (TIMP-1) and metalloproteinase-1 (MMP-1).RESULTS: Compared with saline-treated group, liver fibrosis rats treated with GbE had decreased serum total bilirubin (P<0.01) and aminotransferase levels (P<0.01) and increased levels of serum albumin (P<0.01). Microscopic studies revealed that the livers of rats receiving GbE showed allieviation in fibrosis (P<0.05) as well as expression of αSMA (P<0.01). The liver collagen and reticulum contents were lower in rats treated with GbE than saline-treated group (P<0.01). RT-PCR revealed that the level of TIMP-1 decreased while the level of MMP-1 increased in GbE group.CONCLUSION: Administration of GbE improved CCl4-induced liver fibrosis. It is possibly attributed to its effect of inhibiting the expression of TIMP-1 and promoting the apoptosis of hepatic stellate cells.

  13. Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats

    Directory of Open Access Journals (Sweden)

    Mohammed Al-Yahya

    2013-01-01

    Full Text Available The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH on carbon tetrachloride (CCl4 induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and β-carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2′,7′-dichlorofluorescein (DCF toxicity in ex vivo test.

  14. Bone marrow cells ameliorate liver fibrosis and express albumin after transplantation in CCl 4 -induced fibrotic liver

    Directory of Open Access Journals (Sweden)

    Gibran Ali

    2012-01-01

    Full Text Available Background/Aim: We investigated the effect of bone marrow-derived stem cell (BMSC transplantation on carbon tetrachloride (CCl 4 -induced liver fibrosis. Patients and Methods: BMSCs of green fluorescent protein (GFP mice were transplanted into 4-week CCl 4 -treated C57BL/6 mice directly to the liver, and the mice were treated for 4 more weeks with CCl 4 (total, 8 weeks. After sacrificing the animals, quantitative data of percentage fibrosis area and the number of cells expressing albumin was obtained. One-way analysis of variance was applied to calculate the significance of the data. Results: GFP expressing cells clearly indicated migrated BMSCs with strong expression of albumin after 28 days post-transplantation shown by anti-albumin antibody. Double fluorescent immunohistochemistry showed reduced expression of αSMA on GFP-positive cells. Four weeks after BMSC transplantation, mice had significantly reduced liver fibrosis as compared with that of mice treated with CCl 4 assessed by Sirius red staining. Conclusion: Mice with BMSC transplantation with continuous CCl 4 injection had reduced liver fibrosis and a significantly improved expression of albumin compared with mice treated with CCl 4 alone. These findings strengthen the concept of cellular therapy in liver fibrosis.

  15. Protective effect of Tetracera scandens L.leaf extract against CCl4-induced acute liver injury in rats

    Institute of Scientific and Technical Information of China (English)

    Tung; Bui; Thanh; Hai; Nguyen; Thanh; Hue; Pham; Thi; Minh; Huong; Le-Thi-Thu; Huong; Duong; Thi; Ly; Loi; Vu; Duc

    2015-01-01

    Objective:To investigate the protective potential of ethanolic extracts of Tetracera scandens L.(T.scandens) against CCl4 induced oxidative stress in liver tissues.Methods:Dried leaf powder of T.scandens was extracted with ethanol and concentrated to yield a dry residue.Rats were administered with 100 mg/kg of ethanolic extracts orally once daily for one week.Animals were subsequently administered with a single dose of CCl4(I mL/kg body weight,intraperitoneal injection).Various assays,such as serum levels of alanine aminotransferase,aspartate aminotransferase,lipid peroxidation,protein oxidation(carbonyl protein group),tumor necrosis factor alpha,catalase,superoxide dismutase,and glutathione peroxidase,were used to assess damage caused by CCl4 and the protective effects of the ethanol extract on liver tissues.Results:Hepatotoxicity induced by CCl4 was evidenced by a significant increase in serum aspartate aminotransferase and alanine aminotransferase level,lipid peroxidation,protein carbonyl group,and tumor necrosis factor alpha,as well as decreased activity of the hepatic antioxidant enzymes(catalase.superoxide dismutase.and glutathione peroxidase).Treatment with ethanolic T.scandens extracts prevented all of these typically observed changes in CCl4-treated rats.Conclusions:Our findings indicate that T.scandens has a significant protective effect against CCl4 induced hepatotoxicity in rat.which may be due to its antioxidant properties.

  16. The Increased Expression of CCL20 and CCR6 in Rectal Mucosa Correlated to Severe Inflammation in Pediatric Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Keiichi Uchida

    2015-01-01

    Full Text Available Background/Aims. The aim of this study is to clarify the differences of CCL20 and CCR6 expression, chemokine correlated to intestinal homeostasis, between pediatric and adult ulcerative colitis (UC patients. Methods. Onehundred forty-one patients who underwent proctocolectomy were divided to two groups including childhood-onset UC (CUC, <16 years old, n=24 and adult-onset UC (AUC, ≧16 years old, n=117. A total of 141 formalin-fixed, paraffin-embedded tissue samples of rectum were obtained from these patients. Histological inflammation of rectum in resected specimen was evaluated by using Geboes histological assessment. In immunohistochemistry study, the CCL20 expression was evaluated by intensity and the stained area, and the CCR6 expression was evaluated by lymphocytes infiltration pattern. Results. CCL20 score and CCR6 positive lymphocytes infiltration pattern were statistically significantly correlated with histological inflammation severity of UC in all patients (P<0.05. CCL20 and CCR6 expression in CUC were statistically significantly higher than that in AUC in all or pathologically severe cases (P<0.05. Conclusions. CCL20 and CCR6 may play a significant role in local damage and pathological changes in UC especially pediatric patients. In the future, our understanding of the differences in CCL-CCR6 interaction between adults and children may lead to the pathogenesis of IBD.

  17. Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

    Institute of Scientific and Technical Information of China (English)

    Robert DOMITROVI(C); Hrvoje JAKOVAC; Vanja VASILJEV MARCHESI; Sanda VLADIMIR-KNE(Z)EVI(C); Olga CVIJANOVI(C); (Z)arko TADI(C); (Z)eljko ROMI(C); Dario RAHELI(C)

    2012-01-01

    Aim:To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl4-induced liver damage in mice.Methods:BALB/cN mice were intraperitoneally administered rutin (10,50,and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days,followed by the intraperitoneal injection of CCl4 in olive oil (2 mL/kg,10% v/v).The animals were sacrificed 24 h later.Blood was collected for measuring the activities of ALT and AST,and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity,GSH and protein concentrations and also for immunoblotting.Portions of the livers were used for histology and immunohistochemistry. Results:Pretreatment with rutin and,to a lesser extent,with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl4-intoxicated mice.Quercetin prevented the decrease in Cu/Zn SOD activity in CCl4-intoxicated mice more potently than rutin.However,it was less effective in the suppression of nitrotyrosine formation.Quercetin and,to a lesser extent,rutin attenuated the inflammation in the liver by down-regulating the CCl4-induced activation of nuclear factor-kappa B (NF-κB),tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2).The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin.Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers,although quercetin was less effective than rutin at an equivalent dose.Quercetin more potently suppressed the expression of transforming growth factor-β1 (TGF-β1) than rutin.Conclusion:Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and antiinflammatory activities and antifibrotic potential than quercetin,which may be attributed to the presence of a

  18. Hepatoprotective potential of kumaryasava and its concentrate against CCl4-induced hepatic toxicity in Wistar rats

    Science.gov (United States)

    Khan, Mohammad Ahmed; Gupta, Arun; Sastry, J. L. N.; Ahmad, Sayeed

    2015-01-01

    Objective: Kumaryasava (KS) is a marketed Ayurvedic formulation containing Aloe vera as the main ingredient. It has been used widely for the treatment of liver disorders; however, there is a lack of modern scientific data on hepatoprotection. The recommended dose of KS is high and up to 60 mL/day. The present study describes the preparation of new KS concentrate and evaluation of comparative hepatoprotective activity of KS and prepared KS concentrate at one-third of KS dose against CCl4-induced hepatic toxicity. Materials and Methods: Animals were divided into different groups (n = 6). The first group received normal saline (control) 1.0 mL/Kg/day p.o. for 10 days. The second group (toxicant) was given normal saline 1.0 mL/Kg/day p.o. for 10 days with CCl4 in olive oil (1:1 v/v) at 1.0 mL/Kg/day p.o. Third, fourth, and fifth groups received KS, KS concentrate and a marketed formulation as standard) at doses of 5.0 mL/Kg/day p.o., 1.6 mL/Kg/day p.o., and 100 mL/Kg/day p.o. (tablet suspended in water using 0.1% carboxymethyl cellulose) respectively for 10 days along with CCl4 as given to the toxicant group. On the 11th day, blood was withdrawn from retro-orbital plexus and serum was separated for biochemical estimation of serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), and albumin levels. Later, animals were sacrificed under high dose of anesthesia to remove liver tissue, which were removed and washed with ice cold saline for the estimation of lipid peroxidation. Liver tissue from each group was also fixed in 10% formalin for histopathological analysis. Results: Results demonstrated that both KS and KS concentrate showed the protection against CCl4-induced hepatic toxicity. This was evident from the reduction in serum SGOT, SGPT, ALP levels, and elevation in serum albumin levels observed post treatment of CCl4 treated rats with KS and KS concentrate, which were supported by histopathological data

  19. Intestinal permeability assessed by 51Cr-EDTA in rats with CCl4 - induced cirrhosis Permeabilidade intestinal ao 51-Cr-EDTA em ratos com cirrose induzida por CCl4

    Directory of Open Access Journals (Sweden)

    Ana Regina L. Ramos

    2010-06-01

    Full Text Available CONTEXT: The straight relationship between cirrhosis and impaired intestinal barrier has not been elucidated yet. OBJECTIVES: To verify 51Cr-EDTA-intestinal permeability in rats with CCl4-induced cirrhosis and controls. METHOD: Fifty male Wistar rats weighing 150-180 g were separated in three groups: 25 animals received CCl4 0.25 mL/kg with olive oil by gavage with 12 g/rat/day food restriction for 10 weeks (CCl4-induced cirrhosis; 12 received the same food restriction for 10 weeks (CCl4-non exposed. Other 13 rats received indomethacin 15 mg/kg by gavage as positive control of intestinal inflammation. RESULTS: The median (25-75 interquartile range 51Cr-EDTA-IP values of cirrhotic and CCl4-non exposed rats were 0.90% (0.63-1.79 and 0.90% (0.60-1.52 respectively, without significant difference (P = 0.65. Animals from indomethacin group showed 51Cr-EDTA-IP, median 7.3% (5.1-14.7, significantly higher than cirrhotic and CCl4-non exposed rats (PCONTEXTO: A relação direta entre cirrose e alterações na barreira intestinal ainda não foi devidamente esclarecida. OBJETIVO: Verificar a permeabilidade intestinal ao 51Cr-EDTA em ratos com cirrose induzida por tetracloreto de carbono (CCl4 e controles. MÉTODO: Cinquenta ratos Wistar machos pesando 150-180 g foram separados em três grupos: 25 animais receberam CCl4 0,25 mL/kg diluído em óleo de oliva por gavagem com restrição dietética de 12 g/rato/dia por 10 semanas (grupo cirrose induzida por CCl4; 12 receberam a mesma restrição dietética por 10 semanas (grupo não exposto ao CCl4. Outros 13 ratos receberam indometacina 15 mg/kg por gavagem como controle positivo de inflamação intestinal. RESULTADOS: A mediana (intervalo interquartil 25-75 dos valores de permeabilidade intestinal ao 51Cr-EDTA dos grupos cirrose induzida por CCl4 e não exposto ao CCl4 foram 0,90% (0,63-1,79 e 0,90% (0,60-1,52, respectivamente, sem significância estatística (P = 0,65. Os animais do grupo indometacina

  20. Effect of Tuiyin Soup on CCL17 in Peripheral Blood and Lesions of Psoriasis%退银汤对寻常性银屑病患者外周血及皮损中CCL17的影响

    Institute of Scientific and Technical Information of China (English)

    刘海琴; 盛国荣; 谢勇

    2014-01-01

    目的:探讨退银汤对寻常性银屑病外周血及皮损中胸腺和调控活化的趋化因子(thymus and activation regulated chemokine,TRAC,又称CC chemokine ligand 17,CCL17)表达水平的影响。方法:采用双抗体夹心酶联免疫吸附法检测50例寻常性银屑病患者在使用退银汤治疗前后外周血血清CCL17水平,与40例正常对照组进行比较;另检测30例寻常性银屑病患者在使用退银汤治疗前后皮损组织液CCL17水平,与20例正常对照组进行比较。结果:治疗后,寻常性银屑病患者血清和皮损组织液CCL17表达水平分别与治疗前比较,差异均有统计学意义(P<0.01);治疗前、后进行期与稳定期银屑病患者外周血CCL17分别比较,差异也均有统计学意义(P<0.01),但治疗前进行期与稳定期银屑病患者皮损组织液CCL17表达水平比较,差异有统计学意义(P<0.01);而治疗后比较,差异无统计学意义(P>0.05)。以上CCL17表达水平均与患者相应的PASI呈正相关。结论:退银汤可以降低寻常性银屑病血清及皮损组织液中CCL17的表达水平。%Objective: To study the expression level of thymus and activation regulated chemokine (which is also called as CCL17) in peripheral blood and lesions of patients with psoriasis vulgaris who re_ceived Tuiyin Soup therapy. Methods: Double antibody sandwich-enzyme linked immunosorbent assay was used to detect peripheral blood levels of CCL17 in 50 cases of psoriasis vulgaris before and after treatment with Tuiyin Soup, and 40 cases of the control group were also detected. Besides, the levels of CCL17 in lesions of 30 psoriasis vulgaris were detected before and after treatment with Tuiyin Soup, and 20 cases of the control group were also detected. Results: Before treatment, the expression levels of CCL17 in the serum and the lesions were both higher than those of the control groups. After treatment, the serum and

  1. KEY COMPARISON: Final report on CCL-K6: Calibration of coordinate measuring machine two-dimensional artifacts (ball & bore plates)

    Science.gov (United States)

    Viliesid, Miguel

    2009-01-01

    The Mutual Recognition Arrangement of the CIPM indicates that a metrological equivalence of national measurement standards and calibration certificates issued by national metrology institutes (NMIs) should be established by a set of key comparisons chosen and organized by the Consultative Committees of the Comité Internationale des Poids et Mesures on key techniques. The CCL (Comité Consultative de Longueur), identified several key comparisons in the field of dimensional metrology. In particular, it decided that a coordinate measuring machine (CMM) two-dimensional (2-D) artifact should be carried out. CENAM (Centro Nacional de Metrología) was designated as pilot laboratory and NMIs of signatories of the Metre Convention were invited to participate. The comparison is aimed to support the Calibration and Measurement Capabilities (CMCs) claims of NMIs for CMM 2-D standards calibration. Twelve NMIs from four Regional Metrology Organizations finished the comparison and one withdrew. The final participants were as follows: NMIA (CSIRO), Australia INMS-NRC, Canada NIM, China CMI, Czech Republic BNM-LNE, France PTB, Germany NMIJ (NRLM), Japan NMi, Netherlands VNIIM, Russia NPL, United Kingdom NIST, USA (1) CENAM, Mexico (1). A Draft B report was circulated among the participants and, after review and approval by all of the participants, it became the final report. It comprises all the information about the comparison: the measurement results, the choice of a Key Comparison Reference Value, the estimation of its uncertainty, the performance of each participant with respect to this value and the Birge ratio for each measurand of the two artifacts. It was decided afterwards at CCL that the exercise be classed as a supplementary comparison but the reference of CCL-K6 was kept. In an Appendix the equivalences of all measurands of each laboratory with respect to the reference value are reported for both artifacts, as well as the pairwise equivalences between laboratories for

  2. Theory and computational science

    International Nuclear Information System (INIS)

    The theoretical and computational science carried out at the Daresbury Laboratory in 1984/5 is detailed in the Appendix to the Daresbury Annual Report. The Theory, Computational Science and Applications Groups, provide support work for the experimental projects conducted at Daresbury. Use of the FPS-164 processor is also described. (U.K.)

  3. Astrocyte-Derived CCL2 is Associated with M1 Activation and Recruitment of Cultured Microglial Cells

    Directory of Open Access Journals (Sweden)

    Mingfeng He

    2016-02-01

    Full Text Available Background/Aims: Microglia are an essential player in central nervous system inflammation. Recent studies have demonstrated that the astrocytic chemokine, CCL2, is associated with microglial activation in vivo. However, CCL2-induced microglial activation has not yet been studied in vitro. The purpose of the current study was to understand the role of astrocyte-derived CCL2 in microglial activation and to elucidate the underlying mechanism(s. Methods: Primary astrocytes were pre-treated with CCL2 siRNA and stimulated with TNF-α. The culture medium (CM was collected and added to cultures of microglia, which were incubated with and without CCR2 inhibitor. Microglial cells were analyzed by quantitative RT-PCR to determine whether they polarized to the M1 or M2 state. Microglial migratory ability was assessed by transwell migration assay. Results: TNF-α stimulated the release of CCL2 from astrocytes, even if the culture media containing TNF-α was replaced with fresh media after 3 h. CM from TNF-α-stimulated astrocytes successfully induced microglial activation, which was ascertained by increased activation of M1 and enhanced migration ability. In contrast, CM from astrocytes pretreated with CCL2 siRNA showed no effect on microglial activation, compared to controls. Additionally, microglia pre-treated with RS102895, a CCR2 inhibitor, were resistant to activation by CM from TNF-α-stimulated astrocytes. Conclusion: This study demonstrates that the CCL2/CCR2 pathway of astrocyte-induced microglial activation is associated with M1 polarization and enhanced migration ability, indicating that this pathway could be a useful target to ameliorate inflammation in the central nervous system.

  4. Protective effects of Carissa opaca fruits against CCl4-induced oxidative kidney lipid peroxidation and trauma in rat

    Directory of Open Access Journals (Sweden)

    Sumaira Sahreen

    2015-09-01

    Full Text Available Background: Carbon tetrachloride (CCl4 is a potent nephrotoxin, as it causes acute as well as chronic toxicity in kidneys. Therefore, this study was carried out to assess the pharmacological potential of different fractions of Carissa opaca fruits on CCl4-induced oxidative trauma in the kidney. Methods: The parameters studied in this respect were the kidney function tests viz, serum profile, urine profile, genotoxicity, characteristic morphological findings, and antioxidant enzymatic level of kidneys. Result: The protective effects of various fractions of C. opaca fruits against CCl4 administration were reviewed by rat renal function alterations. Chronic toxicity caused by 8-week treatment of CCl4 to the rats significantly decreased the pH level, activities of antioxidant enzymes, and glutathione contents, whereas a significant increase was found in the case of specific gravity, red blood cells, white blood cells, level of urea, and lipid peroxidation in comparison to control group. Administration of various fractions of C. opaca fruit with CCl4 showed protective ability against CCl4 intoxication by restoring the urine profile, activities of antioxidant enzymes, and lipid peroxidation in rat. CCl4 induction in rats also caused DNA fragmentation and glomerular atrophy by means of dilation, disappearance of Bowmen's space, congestion in the capillary loops, dilation in renal tubules, and foamy look of epithelial cells of tubular region, which were restored by co-admiration of various fractions of C. opaca. Conclusion: Results revealed that the methanolic fractions of C. opaca are the most potent and helpful in kidney trauma.

  5. Recruitment of CCR6-expressing Th17 cells by CCL20 secreted from plasmin-stimulated macrophages

    Institute of Scientific and Technical Information of China (English)

    Qun Li; Yves Laumonnier; Tatiana Syrovets; Thomas Simmet

    2013-01-01

    In the present study,monocyte-derived human macrophages were differentiated from buffy coats.Na(i)ve CD4+ T-cells enriched from peripheral blood mononuclear cells using anti-CD4 magnetic beads and the autoMACS separation system were polarized under T-helper 17 (Th17)-promoting conditions for 6 days to get Th17 cells.The frequency of Th17 cell differentiation and the expression of C-C chemokine receptor type 6 (CCR6) on Th17 cells were investigated by flow cytometry.Plasmin-triggered induction of macrophage inflammatory protein-3alpha/C-C chemokine ligand 20 (CCL20) genes in macrophages was assessed by reverse transcription-polymerase chain reaction,and secreted protein levels were measured by enzymelinked immunosorbent assay.Th17 cell migration induced by CCL20 secreted from plasmin-stimulated macrophages was tested in vitro by chemotaxis using a transwell system.These results demonstrate that plasmin triggers the expression of chemokine CCL20 messenger RNA and the release of CCL20 protein in human monocyte-derived macrophages,which critically depend on the proteolytic activity of plasmin and activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB signaling pathways.Expression of CCR6 was detected on 87.23 ± 8.6% of Th17 cells in vitro.Similar to chemotaxis triggered by recombinant human CCL20,supernatants collected from plasmin-stimulated macrophage-induced chemotactic migration of Th17 cells,which could be inhibited by an anti-CCL20 neutralizing antibody.These results suggest that plasmin generated in inflamed tissues might elicit production of chemokine CCL20 by human macrophages leading to the recruitmentof CCR6 positive Th17 cells to the inflammatory sites.

  6. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Debbie L.; Gerriets, Joan E. [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Schelegle, Edward S.; Hyde, Dallas M. [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Department of Anatomy, Physiology, and Cell Biology, UC Davis School of Veterinary Medicine, Davis, CA 95616 (United States); Miller, Lisa A., E-mail: lmiller@ucdavis.edu [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Department of Anatomy, Physiology, and Cell Biology, UC Davis School of Veterinary Medicine, Davis, CA 95616 (United States)

    2011-12-15

    Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. -- Highlights: Black-Right-Pointing-Pointer Ozone can modulate the localization of eosinophils in infant allergic airways. Black-Right-Pointing-Pointer Expression of eotaxins within the lung is affected by ozone and allergen exposure. Black-Right-Pointing-Pointer CCL24 induction by

  7. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa

    International Nuclear Information System (INIS)

    Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. -- Highlights: ► Ozone can modulate the localization of eosinophils in infant allergic airways. ► Expression of eotaxins within the lung is affected by ozone and allergen exposure. ► CCL24 induction by ozone and allergen exposure is not linked to eosinophilia.

  8. Elucidating a Key Anti-HIV-1 and Cancer-Associated Axis: The Structure of CCL5 (Rantes) in Complex with CCR5

    Science.gov (United States)

    Tamamis, Phanourios; Floudas, Christodoulos A.

    2014-06-01

    CCL5 (RANTES) is an inflammatory chemokine which binds to chemokine receptor CCR5 and induces signaling. The CCL5:CCR5 associated chemotactic signaling is of critical biological importance and is a potential HIV-1 therapeutic axis. Several studies provided growing evidence for the expression of CCL5 and CCR5 in non-hematological malignancies. Therefore, the delineation of the CCL5:CCR5 complex structure can pave the way for novel CCR5-targeted drugs. We employed a computational protocol which is primarily based on free energy calculations and molecular dynamics simulations, and report, what is to our knowledge, the first computationally derived CCL5:CCR5 complex structure which is in excellent agreement with experimental findings and clarifies the functional role of CCL5 and CCR5 residues which are associated with binding and signaling. A wealth of polar and non-polar interactions contributes to the tight CCL5:CCR5 binding. The structure of an HIV-1 gp120 V3 loop in complex with CCR5 has recently been derived through a similar computational protocol. A comparison between the CCL5 : CCR5 and the HIV-1 gp120 V3 loop : CCR5 complex structures depicts that both the chemokine and the virus primarily interact with the same CCR5 residues. The present work provides insights into the blocking mechanism of HIV-1 by CCL5.

  9. THE ROLE OF ENALAPRIL IN PATHOGENESIS OF CCL4 INDUCED HEPATIC FIBROSIS

    Institute of Scientific and Technical Information of China (English)

    魏红山; 李定国; 陆汉明; 展玉涛; 王志荣; 黄新; 徐芹芳

    2001-01-01

    Objective The present study was designed to examine whether the renin-angiotensin system would be implicated in the development of hepatic fibrosis induced by CCl4. The effects of enalapril on the expression of platelet derived growth factor receptor (PDGFR) in liver tissue were also investigated. Methods 50 Sprague-Dawley rats were randomly divided into 5 groups (control group, model group, and 3 enalapril treated groups ). Except rats of the model group, all rats received subcutanous injection of 40% CCl4 (every 3d for 6 weeks). Rats of enalapril treated groups were given enalapril (10mg/kg, 5mg/kg, 2.5mg/kg per day, orally) for 6 weeks before they were killed. Serum levels of hyaluronic acid (HA) and laminin ( LN) were deterrnined by radioimmunoassay techniques. Van Gieson collagen staining was used to evaluate the extracellular matrix of the liver. The expressions of PDGFR and a-smooth muscle actin ( α-SMA ) were confirmed by immunohistochemical methods. Results Compared with those in the model group, it was found in enalapril treated groups: (1) serum levels of collagen type Ⅳ and LN were significantly reduced (P<0.01); (2) the progression of fibrosis was delayed (P<0.01); (3) the expressions of PDGFR and a-SMA were decreased. Conclusion The renin-angiotensin system was involved in the development of hepatic fibrosis induced by CCl4. Angiotensin-converting enzyme (ACE) inhibitor and enalapril could slow down the rate of hepatic fibrosis. This effect might be due to the ability of this drug in suppressing the expression of PDGFR of liver tissue.

  10. Embryonic stem cells develop into hepatocytes after intrasplenic transplantation in CCl4-treated mice

    Institute of Scientific and Technical Information of China (English)

    Kei Moriya; Masahide Yoshikawa; Ko Saito; Yukiteru Ouji; Mariko Nishiofuku; Noriko Hayashi; Shigeaki Ishizaka; Hiroshi Fukui

    2007-01-01

    AIM: To transplant undifferentiated embryonic stem (ES) cells into the spleens of carbon tetrachloride (CCl4)-treated mice to determine their ability to differentiate into hepatocytes in the liver.METHODS: CCU, 0.5 mL/kg body weight, was injected into the peritoneum of C57BL/6 mice twice a week for 5 wk. In group 1 (n = 12), 1 x 105 undifferentiated ES cells (0.1 mL of 1 x 106/mL solution), genetically labeled with GFP, were transplanted into the spleens 1 d after the second injection. Group 2 mice (n = 12) were injected with 0.2 mL of saline twice a week, instead of CCU, and the same amount of ES cells was transplanted into the spleens. Group 3 mice (n = 6) were treated with CCU and injected with 0.1 mL of saline into the spleen, instead of ES cells. Histochemical analyses of the livers were performed on post-transplantation d (PD) 10, 20, and 30.RESULTS: Considerable numbers of GFP-immunopositive cells were found in the periportal regions in group 1 mice (CCl4-treated) on PD 10, however, not in those untreated with CCl4 (group 2). The GFP-positive cells were also immunopositive for albumin (ALB), alpha-1 antitrypsin, cytokeratin 18, and hepatocyte nuclear factor 4 alpha on PD 20. Interestingly, most of the GFP-positive cells were immunopositive for DLK, a hepatoblast marker, on PD 10. Although very few ES-derived cells were demonstrated immunohistologically in the livers of group 1 mice on PD 30, improvements in liver fibrosis were observed. Unexpectedly, liver tumor formation was not observed in any of the mice that received ES cell transplantation during the experimental period.CONCLUSION: Undifferentiated ES cells developed into hepatocyte-like cells with appropriate integration into tissue, without uncontrolled cell growth.

  11. Genetic and bibliographic information: CCL3L1 [GenLibi

    Lifescience Database Archive (English)

    Full Text Available CCL3L1 chemokine (C-C motif) ligand 3-like 1 human HIV Infections (MeSH); HIV-1 Vir...us Diseases (C02) > RNA Virus Infections (C02.782) > Retroviridae Infections (C02.782.815) > Lentivirus Infections... (C02.782.815.616) > HIV Infections (C02.782.815.616.400) Virus Diseases (C02) > Sexually Transmitted ...Diseases (C02.800) > Sexually Transmitted Diseases, Viral (C02.800.801) > HIV Infections... (C02.800.801.400) Immune System Diseases (C20) > Immunologic Deficiency Syndromes (C20.673) > HIV Infections (C20.673.480) 05A0287080 ...

  12. Genetic polymorphism of CCL2-2510 and susceptibility to enterovirus 71 encephalitis in a Chinese population.

    Science.gov (United States)

    Han, Zhen-liang; Li, Ji-an; Chen, Zong-bo

    2014-09-01

    The study was performed in 36 Chinese patients with enterovirus 71 (EV71) encephalitis and 141 patients with EV71-related hand, foot and mouth disease (HFMD) without encephalitis. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism technique. Patients with EV71 encephalitis had a significantly higher frequency of the CCL2-2510GG genotypes when compared to patients with EV71-related HFMD without encephalitis (66.7% vs. 41.8%, p=0.028). The frequency of CCL2-2510G alleles was also significantly higher among the patients with EV71 encephalitis than among patients with EV71-related HFMD without encephalitis (79.2% vs. 64.9%, OR=2.1, 95% CI=1.1-3.8, P=0.023). Significant differences were found in gender, age, fever days, white blood cell count, C-reactive protein level, blood glucose concentration, and CCL2 level among genotypes of CCL2-2510A/G in EV71-infected patients, but no significant differences were found in alanine aminotransferase, aspartate aminotransferase, or creatine kinase myocardial isozyme levels or in cerebrospinal fluid evaluations (except monocytes) in patients with EV71 encephalitis. These findings suggest that the CCL2-2510G allele is associated with susceptibility to EV71 encephalitis in Chinese patients. PMID:24788844

  13. Tumour necrosis factor α enhances CCL2 and ICAM-1 expression in peripheral nerve microvascular endoneurial endothelial cells

    Directory of Open Access Journals (Sweden)

    Evan B. Stubbs

    2013-02-01

    Full Text Available Recruitment and trafficking of autoreactive leucocytes across the BNB (blood–nerve barrier is an early pathological insult in GBS (Guillain-Barré syndrome, an aggressive autoimmune disorder of the PNS (peripheral nervous system. Whereas the aetiology and pathogenesis of GBS remain unclear, pro-inflammatory cytokines, including TNFα (tumour necrosis factor α, are reported to be elevated early in the course of GBS and may initiate nerve injury by activating the BNB. Previously, we reported that disrupting leucocyte trafficking in vivo therapeutically attenuates the course of an established animal model of GBS. Here, PNMECs (peripheral nerve microvascular endothelial cells that form the BNB were harvested from rat sciatic nerves, immortalized by SV40 (simian virus 40 large T antigen transduction and subsequently challenged with TNFα. Relative changes in CCL2 (chemokine ligand 2 and ICAM-1 (intercellular adhesion molecule 1 expression were determined. We report that TNFα elicits marked dose- and time-dependent increases in CCL2 and ICAM-1 mRNA and protein content and promotes secretion of functional CCL2 from immortalized and primary PNMEC cultures. TNFα-mediated secretion of CCL2 promotes, in vitro, the transendothelial migration of CCR2-expressing THP-1 monocytes. Increased CCL2 and ICAM-1 expression in response to TNFα may facilitate recruitment and trafficking of autoreactive leucocytes across the BNB in autoimmune disorders, including GBS.

  14. Relationship of Genetic Polymorphisms of the Chemokine, CCL5, and Its Receptor, CCR5, with Coronary Artery Disease in Taiwan

    Directory of Open Access Journals (Sweden)

    Ke-Hsin Ting

    2015-01-01

    Full Text Available The chemokine receptor CCR5 polymorphism, which confers resistance to HIV infection, has been associated with reduced risk of cardiovascular disease. However, the association of the chemokine, CCL5, and its receptor, CCR5, polymorphism and coronary artery disease (CAD in the Taiwanese has not been studied. In this study, 483 subjects who received elective coronary angiography were recruited from Chung Shan Medical University Hospital. CCL5-403 and CCR5-59029 were determined by polymerase chain reaction-restriction fragment length polymorphism. We found that CCL5-403 with TT genotype frequencies was significantly associated with the risk of CAD group (odds ratio = 3.063 and p=0.012. Moreover, the frequencies of CCR5-59029 with GG or GA genotype were higher than AA genotype in acute coronary syndrome individuals (odds ratio = 1.853, CI = 1.176–2.921, p=0.008. In conclusion, we found that CCL5-403 polymorphism may increase genetic susceptibility of CAD. CCL5-403 or CCR5-59029 single nucleotide polymorphism may include genotype score and it may predict cardiovascular event.

  15. COMPARATIVE EFFECT BETWEEN CHITOSAN AND CHITOSAN-Cu COMPLEX ON CARBON-TETRACHLORIDE (CCL4 INDUCED LIVER DAMAGE IN RATS

    Directory of Open Access Journals (Sweden)

    El-Habibi, E.M.; Sirag, H.M. and Edrees, G.M.

    2009-09-01

    Full Text Available BACKGROUND: Carbon tetrachloride (CCl4 is a toxic material known to induce lipid peroxidation and liver damage. The possible protective roles that involved by chitosan or chitosan-Cu complex against CCl4 induced liver intoxication were investigated in male rats. RESULTS: CCl4 administred at dose 20 mg/kg body weight i.p., exceed malondialdehyde (MDA and protein carbonyle (PC, depleted superoxide dismutase (SOD and glutathione (GSH, in concomitant with marked increase in investigated liver function parameters , alanine aminotransferase and aspartate aminotransferase (ALT, AST, impaired serum and liver total protein , albumin and globulin. An elevation in serum and hepatic total lipids, total cholesterol, triglycerides and serum LDL and VLDL levels as well as a low level of HDL were recorded. In the same time, there was a significant increase in sodium and iron contents in the serum while a significant decrease in potassium and zinc contents were recorded. Animals pretreated with chitosan (200 mg /kg body weight orally by stomach tube for 21 consecutive days prior to CCl4 challenge significantly attenuated most of the tested parameters, strengthen antioxidant defense system, ameliorated liver function effectively. Chitosan-Cu complex has a protective effect by a higher degree than that of chitosan only. CONCLUSION: These findings suggest that pretreatment with chitosan-Cu complex has higher hepato-protective effects than that of only chitosan against CCl4 induced toxicity in rat.

  16. Investigation on improving characteristics of two-cell SBS system with CCl4/C2H5OH liquid mixture

    Institute of Scientific and Technical Information of China (English)

    Hasi Wu-Li-Ji; Lü Li-Qiang; He Wei-Ming

    2007-01-01

    In order to improve the performance of the two-cell stimulated Brillouin scattering(SBS) system,this paper proposes the methods of using mixtures,which require amplifier media to have small absorption rate,and generator media to have high optical breakdown threshold and Brillouin frequency shift equal to that of the amplification media.The characteristics of the two-cell SBS system are studied experimentally by using CCl4 as amplifier medium and CCl4,C2H5OH and CCl4/C2H5OH liquid mixture as generator medium pumped by Nd:YAG Q-switched laser.The obtained results show that liquid mixture in generator cell improves the power load ability,phase conjugation fidelity,energy reflectivity (ER) and ER stability.

  17. Group IVA phospholipase A(2) deficiency prevents CCl4-induced hepatic cell death through the enhancement of autophagy.

    Science.gov (United States)

    Ishihara, Keiichi; Kanai, Shiho; Tanaka, Kikuko; Kawashita, Eri; Akiba, Satoshi

    2016-02-26

    Group IVA phospholipase A2 (IVA-PLA2), which generates arachidonate, plays a role in inflammation. IVA-PLA2-deficiency reduced hepatotoxicity and hepatocyte cell death in mice that received a single dose of carbon tetrachloride (CCl4) without any inhibitory effects on CCl4-induced lipid peroxidation. An immunoblot analysis of extracts from wild-type mouse- and IVA-PLA2 KO mouse-derived primary hepatocytes that transiently expressed microtubule-associated protein 1 light chain 3B (LC3) revealed a higher amount of LC3-II, a typical index of autophagosome formation, in IVA-PLA2-deficient cells, suggesting the enhancement of constitutive autophagy. IVA-PLA2 may promote CCl4-induced cell death through the suppression of constitutive autophagy in hepatocytes.

  18. ACKR4 on Stromal Cells Scavenges CCL19 To Enable CCR7-Dependent Trafficking of APCs from Inflamed Skin to Lymph Nodes.

    Science.gov (United States)

    Bryce, Steven A; Wilson, Ruairi A M; Tiplady, Eleanor M; Asquith, Darren L; Bromley, Shannon K; Luster, Andrew D; Graham, Gerard J; Nibbs, Robert J B

    2016-04-15

    Dermal dendritic cells and epidermal Langerhans cells are APCs that migrate from skin to draining lymph nodes (LN) to drive peripheral tolerance and adaptive immunity. Their migration requires the chemokine receptor CCR7, which directs egress from the skin via dermal lymphatic vessels and extravasation into the LN parenchyma from lymph in the subcapsular sinus. CCR7 is activated by two chemokines: CCL19 and CCL21. CCL21 alone is sufficient for the migration of APCs from skin to LN. CCL19 and CCL21 also bind atypical chemokine receptor (ACKR) 4. ACKR4-mediated CCL21 scavenging by lymphatic endothelial cells lining the subcapsular sinus ceiling stabilizes interfollicular CCL21 gradients that direct lymph-borne CCR7(+)APCs into the parenchyma of mouse LN. In this study, we show that ACKR4 also aids APC egress from mouse skin under steady-state and inflammatory conditions. ACKR4 plays a particularly prominent role during cutaneous inflammation when it facilitates Langerhans cell egress from skin and enables the accumulation of dermal dendritic cells in skin-draining LN. Stromal cells in mouse skin, predominantly keratinocytes and a subset of dermal lymphatic endothelial cells, express ACKR4 and are capable of ACKR4-dependent chemokine scavenging in situ. ACKR4-mediated scavenging of dermal-derived CCL19, rather than CCL21, is critical during inflammation, because the aberrant trafficking of skin-derived APCs inAckr4-deficient mice is completely rescued by genetic deletion ofCcl19 Thus, ACKR4 on stromal cells aids the egress of APCs from mouse skin, and, during inflammation, facilitates CCR7-dependent cell trafficking by scavenging CCL19.

  19. Antioxidant Potential of Plumieride against CCl4-Induced Peroxidative Damage in Rats

    Directory of Open Access Journals (Sweden)

    Dharmendra Singh

    2014-11-01

    Full Text Available In search of a new potent as an antioxidant from natural sources, plumieride—an iridoid isolated from the methanol extract of the bark of Plumeria bicolor (family Apocynaceae was evaluated for its antioxidant potential against CCl4-induced peroxidative damage in liver of rats. The antioxidant potential was evaluated by using hepatic tissue for SOD (superoxide dismutase, CAT (catalase, GSH (reduced glutathione, GPx (glutathione peroxidase, GR (glutathione reductase and LPO (lipid peroxidation alongwith the concomitant blood serum for AST & ALT (aspartate and alanine transaminases, GGT (gamma glutamyl transpeptidase, ALP (alkaline phosphatase, total bilirubin and total protein contents. All the biochemical parameters were significantly (p ≤ 0.001 altered by CCl4 (0.3 mL/kg body weight/twice a week, intra-peritoneally for 30 days. Simultaneously, oral treatment with plumieride (5, 10 and 20 mg/kg body weight/day for 30 days, restored all the parameters towards a normal level, remarkably. The histological findings of liver sections further corroborated the antioxidant potential of plumieride compared with standard drug-silymarin. In conclusion, plumieride consists of sugar molecules, which have alcoholic groups. Therefore, the alcoholic groups of sugar increase its antioxidant potential through intermolecular hydrogen bonding along with the thiol(SH group of non-protein thiols and enzymes resulting in the restoration of the antioxidant system. Therefore, it might be considered a natural antioxidant against peroxidative damage in rats.

  20. Peripheral Neuropathic Facial/Trigeminal Pain and RANTES/CCL5 in Jawbone Cavitation

    Directory of Open Access Journals (Sweden)

    Johann Lechner

    2015-01-01

    Full Text Available Introduction. In this study, we elucidate the possible causative role of chronic subclinical inflammation in jawbone of patients with atypical facial pain (AFP and trigeminal neuralgia (TRN in the local overexpression of the chemokine regulated on activation and normal T-cell expressed and secreted (RANTES/C-C motif ligand 5 CCL5. Neurons contain opioid receptors that transmit antipain reactions in the peripheral and central nervous system. Proinflammatory chemokines like RANTES/CCL5 desensitize μ-opioid receptors in the periphery sensory neurons and it has been suggested that RANTES modifies the nociceptive reaction. Materials and Methods. In 15 patients with AFP/TRN, we examined fatty degenerated jawbone (FDOJ samples for the expression of seven cytokines by multiplex analysis and compared these results with healthy jawbones. Results. Each of these medullary jawbone samples exhibited RANTES as the only highly overexpressed cytokine. The FDOJ cohort with AFP/TRN showed a mean 30-fold overexpression of RANTES compared to healthy jawbones. Conclusions. To the best of our knowledge, no other research has identified RANTES overexpression in silent inflamed jawbones as a possible cause for AFP/TRN. Thus, we hypothesize that the surgical clearing of FDOJ might diminish RANTES signaling pathways in neurons and contribute to resolving chronic neurological pain in AFP/TRN patients.

  1. Leakage Performance of the GM + CCL Liner System for the MSW Landfill

    Directory of Open Access Journals (Sweden)

    Fan Jingjing

    2014-01-01

    Full Text Available The contaminants in the landfill leachate press pose a grave threat to environment of the soil and the groundwater beneath the landfill. Despite there being strict requirements in relevant provisions of both domestic and foreign countries for the design of the bottom liner system. Pollution of the soil and the groundwater still took place in a number of landfills because of the leakage. To investigate the leakage rate of the liner systems, the minimum design requirements of the liner systems are summarized according to the provisions of four countries, including China, USA, Germany, and Japan. Comparative analyses using one-dimensional transport model are conducted to study the leakage performance of these liner systems composed of geomembrance (GM and compacted clay layer (CCL meeting the relevant minimum design requirements. Then parametric analyses are conducted to study the effects of the hydraulic head, the thickness of GM, the hydraulic conductivity of CCL, and so forth on the leakage performance of the liner system. It is concluded that the liner system designed according to the minimum design requirements of Germany provide the best antileakage performance, while that of Japan performs the lowest. The key parameters affecting the failure time of the liner system are summarized. Finally, some suggestions for the design of the liner systems are made according to the analyses.

  2. Leakage performance of the GM + CCL liner system for the MSW landfill.

    Science.gov (United States)

    Jingjing, Fan

    2014-01-01

    The contaminants in the landfill leachate press pose a grave threat to environment of the soil and the groundwater beneath the landfill. Despite there being strict requirements in relevant provisions of both domestic and foreign countries for the design of the bottom liner system. Pollution of the soil and the groundwater still took place in a number of landfills because of the leakage. To investigate the leakage rate of the liner systems, the minimum design requirements of the liner systems are summarized according to the provisions of four countries, including China, USA, Germany, and Japan. Comparative analyses using one-dimensional transport model are conducted to study the leakage performance of these liner systems composed of geomembrance (GM) and compacted clay layer (CCL) meeting the relevant minimum design requirements. Then parametric analyses are conducted to study the effects of the hydraulic head, the thickness of GM, the hydraulic conductivity of CCL, and so forth on the leakage performance of the liner system. It is concluded that the liner system designed according to the minimum design requirements of Germany provide the best antileakage performance, while that of Japan performs the lowest. The key parameters affecting the failure time of the liner system are summarized. Finally, some suggestions for the design of the liner systems are made according to the analyses. PMID:24719569

  3. Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma.

    Science.gov (United States)

    Hamsten, C; Häggmark, A; Grundström, J; Mikus, M; Lindskog, C; Konradsen, J R; Eklund, A; Pershagen, G; Wickman, M; Grunewald, J; Melén, E; Hedlin, G; Nilsson, P; van Hage, M

    2016-09-01

    Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma. PMID:27145233

  4. Effects of Lawsonia inermis L. (Henna Leaves' Methanolic Extract on CCl4-induced Hepatotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Musab Awad Mohamed

    2016-03-01

    Background: Natural products with therapeutic properties such as plants, minerals and animal products, for many years, were the main sources of drugs for treatment of numerous diseases; hence selection of Lawsonia inermis L. (Henna in order to study its hepatoprotective activity was considered. Objectives: This was an attempt to evaluate the hepatoprotective effect of Lawsonia inermis leaves' methanolic extract on CCl4-induced hepatotoxicity in rats. Methods: The L. inermis leaves' methanolic extract, which obtained by maceration, was orally administered in doses of 100mg/kg and 200mg/kg to the tested animals in order to assess it's effects on serum levels of hepatotoxicity parameters, alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, bilirubin and total proteins along with histopathological liver sections examination, while silymarin (25mg/kg, a potent hepatoprotective drug, was used as standard control. Results: The two doses of the plant extract showed dose-dependent hepatoprotective effect, as evident by the significant reduction (P < 0.05 in serum levels of AST, ALT, ALP and bilirubin along with the improvement in histopathological liver sections compared to CCl4-only treated animals. Conclusion: As experimentally evident, it could be concluded that, this plant material could provide a hepatoprotective effect which could be attributed to its antioxidant properties. [J Intercult Ethnopharmacol 2016; 5(1.000: 22-26

  5. Myeloid IKKβ promotes antitumor immunity by modulating CCL11 and the innate immune response.

    Science.gov (United States)

    Yang, Jinming; Hawkins, Oriana E; Barham, Whitney; Gilchuk, Pavlo; Boothby, Mark; Ayers, Gregory D; Joyce, Sebastian; Karin, Michael; Yull, Fiona E; Richmond, Ann

    2014-12-15

    Myeloid cells are capable of promoting or eradicating tumor cells and the nodal functions that contribute to their different roles are still obscure. Here, we show that mice with myeloid-specific genetic loss of the NF-κB pathway regulatory kinase IKKβ exhibit more rapid growth of cutaneous and lung melanoma tumors. In a BRAF(V600E/PTEN(-/-)) allograft model, IKKβ loss in macrophages reduced recruitment of myeloid cells into the tumor, lowered expression of MHC class II molecules, and enhanced production of the chemokine CCL11, thereby negatively regulating dendritic-cell maturation. Elevated serum and tissue levels of CCL11 mediated suppression of dendritic-cell differentiation/maturation within the tumor microenvironment, skewing it toward a Th2 immune response and impairing CD8(+) T cell-mediated tumor cell lysis. Depleting macrophages or CD8(+) T cells in mice with wild-type IKKβ myeloid cells enhanced tumor growth, where the myeloid cell response was used to mediate antitumor immunity against melanoma tumors (with less dependency on a CD8(+) T-cell response). In contrast, myeloid cells deficient in IKKβ were compromised in tumor cell lysis, based on their reduced ability to phagocytize and digest tumor cells. Thus, mice with continuous IKKβ signaling in myeloid-lineage cells (IKKβ(CA)) exhibited enhanced antitumor immunity and reduced melanoma outgrowth. Collectively, our results illuminate new mechanisms through which NF-κB signaling in myeloid cells promotes innate tumor surveillance. PMID:25336190

  6. Raloxifene suppresses experimental autoimmune encephalomyelitis and NF-κB-dependent CCL20 expression in reactive astrocytes.

    Directory of Open Access Journals (Sweden)

    Rui Li

    Full Text Available Recent clinical data have led to the consideration of sexual steroids as new potential therapeutic tools for multiple sclerosis. Selective estrogen receptor modulators can exhibit neuroprotective effects like estrogen, with fewer systemic estrogen side effects than estrogen, offering a more promising therapeutic modality for multiple sclerosis. The important role of astrocytes in a proinflammatory effect mediated by CCL20 signaling on inflammatory cells has been documented. Their potential contribution to selective estrogen receptor modulator-mediated protection is still unknown. Using a mouse model of chronic neuroinflammation, we report that raloxifene, a selective estrogen receptor modulator, alleviated experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and decreased astrocytic production of CCL20. Enzyme-linked immunosorbent assay, immunohistochemistry imaging and transwell migration assays revealed that reactive astrocytes express CCL20, which promotes Th17 cell migration. In cultured rodent astrocytes, raloxifene inhibited IL-1β-induced CCL20 expression and chemotaxis ability for Th17 migration, whereas the estrogen receptor antagonist ICI 182,780 blocked this effect. Western blotting further indicated that raloxifene suppresses IL-1β-induced NF-κB activation (phosphorylation of p65 and translocation but does not affect phosphorylation of IκB. In conclusion, these data demonstrate that raloxifene provides robust neuroprotection against experimental autoimmune encephalomyelitis, partially via an inhibitory action on CCL20 expression and NF-κB pathways in reactive astrocytes. Our results contribute to a better understanding of the critical roles of raloxifene in treating experimental autoimmune encephalomyelitis and uncover reactive astrocytes as a new target for the inhibitory action of estrogen receptors on chemokine CCL20 expression.

  7. Detection of CCl/sub 4/-induced oxidation of hepatic tissue in vivo by oxygen-18 tracing

    Energy Technology Data Exchange (ETDEWEB)

    Hatch, G.E.; Santrock, J.; Slade, R.; Hayes, J.M.

    1988-01-01

    Oxygen can become a damaging influence in tissues and cells exposed to environmental pollutants. This paper describes the first application of a new technique for tracing oxygen in tissues exposed to pollutants. Carbon tetrachloride (CCl/sub 4/) was found to cause oxidation of liver tissue in rats which was measurable using oxygen-18 labeling procedures. Rats that breathed oxygen-18 while being exposed to CCl/sub 4/ were found to have oxidized lipids, macromolecules, and water-soluble substances in their livers. The techniques outlined in the paper should be useful for elucidating mechanisms of injury and increased aging of tissues exposed to pollutants.

  8. TWEAK activates the non-canonical NFkappaB pathway in murine renal tubular cells: modulation of CCL21.

    Directory of Open Access Journals (Sweden)

    Ana B Sanz

    Full Text Available TWEAK is a member of the TNF superfamily of cytokines that contribute to kidney tubulointerstitial injury. It has previously been reported that TWEAK induces transient nuclear translocation of RelA and expression of RelA-dependent cytokines in renal tubular cells. Additionally, TWEAK induced long-lasting NFkappaB activation suggestive of engagement of the non-canonical NFkappaB pathway. We now explore TWEAK-induced activation of NFkappaB2 and RelB, as well as expression of CCL21, a T-cell chemotactic factor, in cultured murine tubular epithelial cells and in healthy kidneys in vivo. In cultured tubular cells, TWEAK and TNFalpha activated different DNA-binding NFkappaB complexes. TWEAK-induced sustained NFkappaB activation was associated with NFkappaB2 p100 processing to p52 via proteasome and nuclear translocation and DNA-binding of p52 and RelB. TWEAK, but not TNFalpha used as control, induced a delayed increase in CCL21a mRNA (3.5+/-1.22-fold over control and CCL21 protein (2.5+/-0.8-fold over control, which was prevented by inhibition of the proteasome, or siRNA targeting of NIK or RelB, but not by RelA inhibition with parthenolide. A second NFkappaB2-dependent chemokine, CCL19, was upregulates by TWEAK, but not by TNFalpha. However, both cytokines promoted chemokine RANTES expression (3-fold mRNA at 24 h. In vivo, TWEAK induced nuclear NFkappaB2 and RelB translocation and CCL21a mRNA (1.5+/-0.3-fold over control and CCL21 protein (1.6+/-0.5-fold over control expression in normal kidney. Increased tubular nuclear RelB and tubular CCL21 expression in acute kidney injury were decreased by neutralization (2+/-0.9 vs 1.3+/-0.6-fold over healthy control or deficiency of TWEAK (2+/-0.9 vs 0.8+/-0.6-fold over healthy control. Moreover, anti-TWEAK treatment prevented the recruitment of T cells to the kidney in this model (4.1+/-1.4 vs 1.8+/-1-fold over healthy control. Our results thus identify TWEAK as a regulator of non-canonical NFkappa

  9. Impulse Breakdown Characteristics and Cost/Benefit Analysis of $SF_6/CCL_2F_2/C0_2$ Mixtures

    OpenAIRE

    Raghavender, D; Naidu, MS

    1989-01-01

    A comprehensive study has been carried out in $SF_6/CCL_2F_2/C0_2$ mixtures to measure 50% breakdown voltages $(V_5_0)$ using both positive and negative polarity lightning impulse (1.2/50 $\\mu$s) voltages under non-uniform fields (5 mm. rod – 230 mm plane electrode) over a pressure range of 0.1 to 0.5 HPa for a gap spacing of 20 mm. The sum of $SF_6$,and $CCL_2F_2$ concentrations in the mixture was always maintained in the range of 21 to 40%, rest being $CO_2$. Among the different sets of $SF...

  10. Effect of aqueous extract of Tinospora cordifolia on functions of peritoneal macrophages isolated from CCl4 intoxicated male albino mice

    Directory of Open Access Journals (Sweden)

    Sharma Gauri D

    2011-10-01

    Full Text Available Abstract Background The current practice of ingesting phytochemicals for supporting the immune system or fighting infections is based on centuries-old tradition. Macrophages are involved at all the stages of an immune response. The present study focuses on the immunostimulant properties of Tinospora cordifolia extract that are exerted on circulating macrophages isolated from CCl4 (0.5 ml/kg body weight intoxicated male albino mice. Methods Apart from damaging the liver system, carbon tetrachloride also inhibits macrophage functions thus, creating an immunocompromised state, as is evident from the present study. Such cell functions include cell morphology, adhesion property, phagocytosis, enzyme release (myeloperoxidase or MPO, nitric oxide (NO release, intracellular survival of ingested bacteria and DNA fragmentation in peritoneal macrophages isolated from these immunocompromised mice. T. cordifolia extract was tested for acute toxicity at the given dose (150 mg/kg body weight by lactate dehydrogenase (LDH assay. Results The number of morphologically altered macrophages was increased in mice exposed to CCl4. Administration of CCl4 (i.p. also reduced the phagocytosis, cell adhesion, MPO release, NO release properties of circulating macrophages of mice. The DNA fragmentation of peritoneal macrophages was observed to be higher in CCl4 intoxicated mice. The bacterial killing capacity of peritoneal macrophages was also adversely affected by CCl4. However oral administration of aqueous fraction of Tinospora cordifolia stem parts at a dose of 40 mg/kg body weight (in vivo in CCl4 exposed mice ameliorated the effect of CCl4, as the percentage of morphologically altered macrophages, phagocytosis activity, cell adhesion, MPO release, NO release, DNA fragmentation and intracellular killing capacity of CCl4 intoxicated peritoneal macrophages came closer to those of the control group. No acute toxicity was identified in oral administration of the aqueous

  11. CpG-ODNs induces up-regulated expression of chemokine CCL9 in mouse macrophages and microglia

    Digital Repository Service at National Institute of Oceanography (India)

    Ravindran, C.; Cheng, Y.-C.; Liang, S.-M.

    of the experiments. RNA isolation and Quantitative RT-PCR analysis Total RNA extraction from Raw and BV2 cells induced by several Tlr and Tlr9 ligands and kinase inhibitors were made according to the manufacturer protocols (Viogene RNA extraction kit... (Invitrogen) and oligo (dT) 15 primer for 1 h at 42°C or according to manufacturer’s (invitrogen) instructions. Thereafter, equal amounts of cDNA products were amplified for CCl9 expressions. The primers used in this study are CCL9 (forward 5’- AAC AGA...

  12. Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b.

    Science.gov (United States)

    Vergani, Elisabetta; Di Guardo, Lorenza; Dugo, Matteo; Rigoletto, Sara; Tragni, Gabrina; Ruggeri, Roberta; Perrone, Federica; Tamborini, Elena; Gloghini, Annunziata; Arienti, Flavio; Vergani, Barbara; Deho, Paola; De Cecco, Loris; Vallacchi, Viviana; Frati, Paola; Shahaj, Eriomina; Villa, Antonello; Santinami, Mario; De Braud, Filippo; Rivoltini, Licia; Rodolfo, Monica

    2016-01-26

    In melanoma, the adaptative cell response to BRAF inhibitors includes altered patterns of cytokine production contributing to tumor progression and drug resistance. Among the factors produced by PLX4032-resistant melanoma cell lines, CCL2 was higher compared to the sensitive parental cell lines and increased upon drug treatment. CCL2 acted as an autocrine growth factor for melanoma cells, stimulating the proliferation and resistance to apoptosis. In patients, CCL2 is detected in melanoma cells in tumors and in plasma at levels that correlate with tumor burden and lactate dehydrogenase. Vemurafenib treatment increased the CCL2 levels in plasma, whereas the long-term clinical response was associated with low CCL2 levels.Increased CCL2 production was associated with miRNA deregulation in the resistant cells. miR-34a, miR-100 and miR-125b showed high expression in both resistant cells and in tumor biopsies that were obtained from treated patients, and they were involved in the control of cell proliferation and apoptosis. Inhibition of CCL2 and of the selected miRNAs restored both the cell apoptosis and the drug efficacy in resistant melanoma cells. Therefore, CCL2 and miRNAs are potential prognostic factors and attractive targets for counteracting treatment resistance in metastatic melanoma. PMID:26684239

  13. CCL21 Facilitates Chemoresistance and Cancer Stem Cell-Like Properties of Colorectal Cancer Cells through AKT/GSK-3β/Snail Signals

    Directory of Open Access Journals (Sweden)

    Lin-Lin Lu

    2016-01-01

    Full Text Available Some evidence indicated that chemoresistance associates with the acquisition of cancer stem-like properties. Recent studies suggested that chemokines can promote the chemoresistance and stem cell properties in various cancer cells, while the underling mechanism is still not completely illustrated. In our study, we found that CCL21 can upregulate the expression of P-glycoprotein (P-gp and stem cell property markers such as Bmi-1, Nanog, and OCT-4 in colorectal cancer (CRC HCT116 cells and then improve the cell survival rate and mammosphere formation. Our results suggested that Snail was crucial for CCL21-mediated chemoresistance and cancer stem cell property in CRC cells. Further, we observed that CCL21 treatment increased the protein but not mRNA levels of Snail, which suggested that CCL21 upregulates Snail via posttranscriptional ways. The downstream signals AKT/GSK-3β mediated CCL21 induced the upregulation of Snail due to the fact that CCL21 treatment can obviously phosphorylate both AKT and GSK-3β. The inhibitor of PI3K/Akt, LY294002 significantly abolished CCL21 induced chemoresistance and mammosphere formation of HCT116 cells. Collectively, our results in the present study revealed that CCL21 can facilitate chemoresistance and stem cell property of CRC cells via the upregulation of P-gp, Bmi-1, Nanog, and OCT-4 through AKT/GSK-3β/Snail signals, which suggested a potential therapeutic approach to CRC patients.

  14. CCL21 Facilitates Chemoresistance and Cancer Stem Cell-Like Properties of Colorectal Cancer Cells through AKT/GSK-3β/Snail Signals.

    Science.gov (United States)

    Lu, Lin-Lin; Chen, Xiao-Hui; Zhang, Ge; Liu, Zong-Cai; Wu, Nong; Wang, Hao; Qi, Yi-Fei; Wang, Hong-Sheng; Cai, Shao Hui; Du, Jun

    2016-01-01

    Some evidence indicated that chemoresistance associates with the acquisition of cancer stem-like properties. Recent studies suggested that chemokines can promote the chemoresistance and stem cell properties in various cancer cells, while the underling mechanism is still not completely illustrated. In our study, we found that CCL21 can upregulate the expression of P-glycoprotein (P-gp) and stem cell property markers such as Bmi-1, Nanog, and OCT-4 in colorectal cancer (CRC) HCT116 cells and then improve the cell survival rate and mammosphere formation. Our results suggested that Snail was crucial for CCL21-mediated chemoresistance and cancer stem cell property in CRC cells. Further, we observed that CCL21 treatment increased the protein but not mRNA levels of Snail, which suggested that CCL21 upregulates Snail via posttranscriptional ways. The downstream signals AKT/GSK-3β mediated CCL21 induced the upregulation of Snail due to the fact that CCL21 treatment can obviously phosphorylate both AKT and GSK-3β. The inhibitor of PI3K/Akt, LY294002 significantly abolished CCL21 induced chemoresistance and mammosphere formation of HCT116 cells. Collectively, our results in the present study revealed that CCL21 can facilitate chemoresistance and stem cell property of CRC cells via the upregulation of P-gp, Bmi-1, Nanog, and OCT-4 through AKT/GSK-3β/Snail signals, which suggested a potential therapeutic approach to CRC patients. PMID:27057280

  15. HYDROMECHANICS LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — Naval Academy Hydromechanics Laboratory The Naval Academy Hydromechanics Laboratory (NAHL) began operations in Rickover Hall in September 1976. The primary purpose...

  16. The CCL3L1-CCR5 genotype influences the development of AIDS, but not HIV susceptibility or the response to HAART

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Tanmoy [Los Alamos National Laboratory; Stanton, Jennifer [NORTHWESTERN UNIV; Kim, Eun - Young [NORTHWESTERN UNIV; Kunstman, Kevin [NORTHWESTERN UNIV; Phair, John [NORTHWESTERN UNIV; Jacobson, Lisa P [JOHNS HOPKINS UNIV; Wolinsky, Steven M [NORTHWESTERN UNIV

    2008-01-01

    A selective advantage against infectious diseases such as HIV/AIDS is associated with differences in the genes relevant to immunity and virus replication. The CC chemokine receptor 5 (CCR5), the principal coreceptor for HIV, and its chemokine ligands, including CCL3L1, influences the CD4+ target cells susceptibility to infection. The CCL3L1 gene is in a region of segmental duplication on the q-arm of human chromosome 17. Increased numbers of CCL3L1 gene copies that affect the gene expression phenotype might have substantial protective effects. Here we show that the population-specific CCL3L1 gene copy number and the CCR5 {Delta}32 protein-inactivating deletion that categorizes the CCL3L1-CCR5 genotype do not influence HIV/AIDS susceptibility or the robustness of immune recovery after the initiation of highly active antiretroviral therapy (HAART).

  17. 核苷酸补偿对CCl_4致肝纤维化大鼠血清蛋白和尿酸水平的影响

    Institute of Scientific and Technical Information of China (English)

    朱善良

    2012-01-01

    本研究以添加核苷酸的日粮饲喂四氯化碳(CCl4)致肝纤维化大鼠,测定大鼠血清蛋白和尿酸等生化指标变化,以探讨外源核苷酸对CCl4致肝纤维化的干预作用.结果表明,CCl4组大鼠体重均低于或显著低于C组和CCl4+NTs组;CCl4组血清总蛋白含量显著低于CCl4+NTs组和C组,而CCl4+NTs组与C组之间差异不显著.C组、CCl4组和CCl4+NTs组之间的血清A含量存在显著差异,其中C组最高,CCl4+NTs组次之,CCl4组最低.CCl4组和CCl4+NTs组的血清G含量显著高于与C组,而CCl4+NTs组显著高于CCl4组.CCl4+NTs组和CCl4组的A/G比值显著低于C组,而CCl4组与CCl4+NTs组间无显著差异.CCl4组血清UA水平显著低于CCl4+NTs组和C组,而CCl4+NTs组与C组UA水平基本持平.结果提示,日粮补偿核苷酸引起CCl4致肝纤维化大鼠的血清白蛋白、球蛋白和尿酸等生化指标发生了明显变化,这可能是外源核苷酸干预肝纤维化损伤的重要机制之一.

  18. Distinct Upstream Role of Type I IFN Signaling in Hematopoietic Stem Cell-Derived and Epithelial Resident Cells for Concerted Recruitment of Ly-6Chi Monocytes and NK Cells via CCL2-CCL3 Cascade.

    Directory of Open Access Journals (Sweden)

    Erdenebileg Uyangaa

    Full Text Available Type I interferon (IFN-I-dependent orchestrated mobilization of innate cells in inflamed tissues is believed to play a critical role in controlling replication and CNS-invasion of herpes simplex virus (HSV. However, the crucial regulators and cell populations that are affected by IFN-I to establish the early environment of innate cells in HSV-infected mucosal tissues are largely unknown. Here, we found that IFN-I signaling promoted the differentiation of CCL2-producing Ly-6Chi monocytes and IFN-γ/granzyme B-producing NK cells, whereas deficiency of IFN-I signaling induced Ly-6Clo monocytes producing CXCL1 and CXCL2. More interestingly, recruitment of Ly-6Chi monocytes preceded that of NK cells with the levels peaked at 24 h post-infection in IFN-I-dependent manner, which was kinetically associated with the CCL2-CCL3 cascade response. Early Ly-6Chi monocyte recruitment was governed by CCL2 produced from hematopoietic stem cell (HSC-derived leukocytes, whereas NK cell recruitment predominantly depended on CC chemokines produced by resident epithelial cells. Also, IFN-I signaling in HSC-derived leukocytes appeared to suppress Ly-6Ghi neutrophil recruitment to ameliorate immunopathology. Finally, tissue resident CD11bhiF4/80hi macrophages and CD11chiEpCAM+ dendritic cells appeared to produce initial CCL2 for migration-based self-amplification of early infiltrated Ly-6Chi monocytes upon stimulation by IFN-I produced from infected epithelial cells. Ultimately, these results decipher a detailed IFN-I-dependent pathway that establishes orchestrated mobilization of Ly-6Chi monocytes and NK cells through CCL2-CCL3 cascade response of HSC-derived leukocytes and epithelium-resident cells. Therefore, this cascade response of resident-to-hematopoietic-to-resident cells that drives cytokine-to-chemokine-to-cytokine production to recruit orchestrated innate cells is critical for attenuation of HSV replication in inflamed tissues.

  19. Contracting C2C12 myotubes release CCL2 in an NF-κB-dependent manner to induce monocyte chemoattraction.

    Science.gov (United States)

    Miyatake, Shouta; Bilan, Philip J; Pillon, Nicolas J; Klip, Amira

    2016-01-15

    Muscle inflammation following exercise is characterized by expression of inflammatory cytokines and chemokines. Exercise also increases muscle macrophages derived from circulating monocytes. However, it is unknown whether muscle cells themselves attract circulating monocytes, or what is the underlying mechanism. We used an in vitro system of electrical stimulation (ES) causing C2C12 myotube contraction to explore whether monocyte chemoattraction ensues and investigated the mediating chemoattractants. Conditioned medium from ES-contracted myotubes caused robust chemoattraction of THP-1 monocytes across Boyden chambers. Following ES, expression of several known monocyte chemokines [C-C motif ligand 2 (CCL2) and C-X-C motif ligand (CXCL)1, -2, and -5] was elevated, but of these, only recombinant CCL2 effectively reproduced monocyte migration. Electrically stimulated myotubes secreted CCL2, and neutralization of CCL2 in conditioned medium or antagonizing the CCL2 receptor (CCR2) in THP-1 monocytes inhibited ES-induced monocyte migration. N-benzyl-p-toluene sulfonamide (BTS), a myosin II-ATPase inhibitor, prevented ES-induced myotube contraction but not CCL2 gene expression and secretion. The membrane-permeant calcium chelator BAPTA-AM reduced ES-induced CCL2 secretion. Hence, electrical depolarization, rather than mechanical contraction, drives the rise in CCL2, with partial calcium input. ES activated the NF-κB pathway; NF-κB inhibitors reduced ES-induced CCL2 gene expression and secretion and repressed ES-induced THP-1 chemoattraction. Thus, electrically stimulated myotubes chemoattract monocytes through NF-κB-regulated CCL2 secretion. PMID:26554595

  20. A novel role of hematopoietic CCL5 in promoting triple-negative mammary tumor progression by regulating generation of myeloid-derived suppressor cells

    Institute of Scientific and Technical Information of China (English)

    Yan Zhang; Dandan Lv; Ha-Jeong Kim; Robert A Kurt; Wen Bu; Yi Li; Xiaojing Ma

    2013-01-01

    CCL5 is a member of the CC chemokine family expressed in a wide array of immune and non-immune cells in response to stress signals.CCL5 expression correlates with advanced human breast cancer.However,its functional significance and mode of action have not been established.Here,we show that CCL5-deficient mice are resistant to highly aggressive,triple-negative mammary tumor growth.Hematopoietic CCL5 is dominant in this phenotype.The absence of hematopoietic CCL5 causes aberrant generation of CD11b+/Gr-1+,myeloid-derived suppressor cells (MDSCs) in the bone marrow in response to tumor growth by accumulating Ly6Chi and Ly6G+ MDSCs with impaired capacity to suppress cytotoxicity of CD8+ T cells.These properties of CCL5 are observed in both orthotopic and spontaneous mammary tumors.Antibody-mediated systemic blockade of CCL5 inhibits tumor progression and enhances the efficacy of therapeutic vaccination against non-immunogenic tumors.CCL5 also helps maintain the immunosuppressive capacity of human MDSCs.Our study uncovers a novel,chemokine-independent activity of the hematopoietically derived CCL5 that promotes mammary tumor progression via generating MDSCs in the bone marrow in cooperation with tumor-derived colony-stimulating factors.The study sheds considerable light on the interplay between the hematopoietic compartment and tumor niche.Because of the apparent dispensable nature of this molecule in normal physiology,CCL5 may represent an excellent therapeutic target in immunotherapy for breast cancer as well as a broad range of solid tumors that have significant amounts of MDSC infiltration.

  1. Effect of Misgurnus anguillicaudatus Lyophilized Power on Liver Fibrosis Induced by CCl 4 in Mice%泥鳅冻干粉抗CCl4小鼠肝纤维化作用

    Institute of Scientific and Technical Information of China (English)

    张倩; 商萌萌; 凌去非; 刘春宇

    2014-01-01

    To study the effect of Misgurnus anguillicaudatus lyophilized power on liver fibrosis, the model in mice was established by using CCl4. Given different doses of Misgurnus anguillicaudatus lyophilized power, the serum ALT and AST activities and tissue Hyp content were detected. The pathological changes of liver were observed. Results showed that the AST and ALT activities and Hyp levels were significantly decreased (P<0.05) in three doses groups of Misgurnus Anguillicaudatus lyophilized power, compared with the model group. The pathological improvements were observed. The fibrogenesis in liver tissues were markedly reduced and the formation of liver pseudoluboli was alleviated. The Misgurnus anguillicaudatus lyophilized power can prevent the formation of liver fibrosis induced by CCl4 in mice.%采用CCl4小鼠肝纤维化模型,给予不同剂量泥鳅冻干粉,检测小鼠血清中ALT、AST活性及肝组织中羟脯氨酸(Hyp)含量,并观察肝组织病理变化,探讨泥鳅冻干粉抗CCl4小鼠肝纤维化作用。结果表明,与模型组相比,泥鳅粉冻干粉明显降低CCl4诱导的肝纤维化小鼠血清ALT、AST活性,显著降低肝组织Hyp含量(P<0.05)。病理学观察结果,泥鳅粉冻干粉给药组小鼠胶原纤维沉积明显减轻,假小叶结构明显减少。泥鳅冻干粉能预防小鼠肝纤维化的形成,具有抗肝纤维化作用。

  2. Dramatic Substituent Effect on the CCL-catalyzed Kinetic Resolution of 1-Aryl-2,3-allenols

    Institute of Scientific and Technical Information of China (English)

    XU, Dai-Wang(徐代旺); LI, Zu-Yi(李祖义); MA, Sheng-Ming(麻生明)

    2004-01-01

    Optically active 1-aryl-2,3-allenols were obtained via CCL-mediated kinetic resolution of the racemic allenols. The substitution pattern of the aromatic ring, regarding to both the type of the substituent and its position on the aromatic ring, was found to be critical for the kinetic resolution of 1-aryl-2,3-allenols.

  3. Protective effects of polyphenols-enriched extract from Huangshan Maofeng green tea against CCl4-induced liver injury in mice.

    Science.gov (United States)

    Cui, Yanmang; Yang, Xingbin; Lu, Xinshan; Chen, Jinwen; Zhao, Yan

    2014-09-01

    The study was to characterize the polyphenolic composition, antioxidant properties, and hepatoprotective effects of a polyphenols-enriched extract (HMTP) from Huangshan Maofeng green tea. HPLC analysis showed that three predominantly polyphenolic compounds present in HMTP were epigallocatechin (271.2 μg/mg extract), rutin (239.3 μg/mg) and epicatechin (89.3 μg/mg). HMTP was shown to exhibit strong scavenging activities against DPPH, O2(-), and OH, and ferric-reducing antioxidant power in vitro. Administration of HMTP at 200, 400 and 800 mg/kg bw in mice prior to CCl4 injury significantly decreased the CCl4-induced elevation of serum ALT, AST and ALP activities, and prevented an increase in hepatic MDA levels (p<0.05). Mice with HMTP pretreatment displayed a better profile of hepatosomatic index and the improved GSH-Px and SOD activities in the liver, relative to CCl4-intoxicated mice. Liver pathological observation also confirmed the protection on CCl4-caused histological alteration, suggesting that HMTP has potential to be explored as valuable hepatoprotective function food.

  4. CCl4 induces tissue-type plasminogen activator in rat brain; protective effects of oregano, rosemary or vitamin E.

    Science.gov (United States)

    Lavrentiadou, Sophia N; Tsantarliotou, Maria P; Zervos, Ioannis A; Nikolaidis, Efstathios; Georgiadis, Marios P; Taitzoglou, Ioannis A

    2013-11-01

    The high metabolic rate and relatively low antioxidant defenses of the lipid-rich brain tissue render it highly susceptible to reactive oxygen species (ROS) and oxidative stress, whereas the implication of ROS in the pathogenesis of several diseases in the central nervous system is well-established. The plasminogen activator (PA) system is a key modulator of extracellular proteolysis, extracellular matrix remodeling and neuronal cell signaling and has been implicated in the pathogenesis of these diseases. This study evaluates the role of tissue-type PA (t-PA) in oxidative stress and the protective role of dietary antioxidants in the rat brain. We used the CCl4 experimental model of ROS-induced lipid peroxidation and evaluated the antioxidant effect of oregano, rosemary or vitamin E. CCl4-treated Wistar rats exhibited elevated brain t-PA activity, which was decreased upon long-term administration of oregano, rosemary or vitamin E. PA inhibitor-1 (PAI-1) activity was also slightly elevated by CCl4, but this increase was not affected by the antioxidants. We hypothesize that the CCl4-induced t-PA activity indicates extracellular proteolytic activity that may be linked to neuronal cell death and brain damage. Vitamin E or antioxidants present in oregano or rosemary are effective in inhibiting t-PA elevation and can be considered as a potential protection against neuronal damage. PMID:23831191

  5. Total toxicity equivalents emissions of SF6, CHF3, and CCl2F2 decomposed in a RF plasma environment.

    Science.gov (United States)

    Wang, Ya-Fen; Shih, Minliang; Tsai, Cheng-Hsien; Tsai, Perng-Jy

    2006-03-01

    Sulfur hexafluorine compound (SF6), trifluoromethane (CHF3) and diclorodifluoromethane (CCl2F2) are extensively used in the semiconductor industry. They are global warming gases. Most studies have addressed the effective decomposition of fluorine compounds, rather than the toxicity of decomposed by-products. Hence, the concepts of toxicity equivalents (TEQs) were applied in this work. The results indicated that HF and SiF4 were the two greatest contributors of TEQ to the SF6/H2/Ar plasma system, while F2 and SiF4 were the two greatest contributors to the SF6/O2/Ar system. Additionally, SiF4 and HF were the two greatest contributors of TEQ to both the CHF3/H2/Ar and CHF3/O2/Ar plasma systems. HF and HCl were the two greatest contributors of TEQ to the CCl2F2/H2/Ar plasma system, and Cl2 and COCl2 were the two greatest contributors to the CCl2F2/O2/Ar system. HCl and HF can be recovered using wet scrubbing, which reduces the toxicity of these emission gases. Consequently, the hydrogen-based plasma system was a better alternative for treating gases that contained SF6, CHF3 and CCl2F2 from the TEQs point of view. PMID:16084562

  6. PROTECTIVE ABILITY OF MOMORDICA CHARANTIA L AGAINST CCL4 INDUCED HEPATIC DAMAGE IN RATS

    Directory of Open Access Journals (Sweden)

    Pingale Shirish S

    2010-12-01

    Full Text Available The aim of this study is to evaluate the efficacy of Momordica charantia on the experimental hepatotoxicity induced by carbon tetrachloride (CCl4. Carbon tetrachloride was administered once and simultaneously suspension of dry fruit powder was prepared in aqueous medium and was daily administered at a dose level of 1mg/kg body weight for 4 days. Silymarin was used as a standard drug for this study. Administration of carbon tetrachloride showed significant changes in the levels of serum aminotransferase, alkaline phosphatase, bilirubin and total proteins levels, however necrosis, collagen deposition and altered hepatic architecture were also observed. Markers of liver injury, altered aminotransferase, alkaline phosphatase, bilirubin etc. and morphological changes such as necrosis and collagen deposition were significantly decreased in the rats treated with Momordica charantia fruit powder. These results suggest that the Momordica charantia showed hepatoprotective effect on carbon tetrachloride induced hepatic damage and may be a potential clinical application for treatment of liver diseases.

  7. Crystal structure of erbium trichloroacetate Er(CCl3COO)·2H2O

    International Nuclear Information System (INIS)

    X-ray structure study of Er(CCl3COO)3x2H2O crystals is conducted (SYNTEX P21 autodiffractometer, MoKα-radiation). The crystals are of triclinic syngony: a11.697 (4), b=12.790 (4), c=15223 (4) A, α=70.67 (3), β=77.80 (3), γ=6561 (3)deg; space group P1, Z=4. There are two crystallographically independent types of erbium atoms with coordination numbers 7 and 8, respectively, in the unit cell. These atoms are linked by tetra- and double-carboxylated cross-links in the endless chains, while water molecules complete the metal coordination polyhedron is within 2.259-2.393 A interval, while in seven-coordination - within 2.229-2.267 A interval. Er-H2O distances constitute 2.389-2.534 A

  8. Comparative Study of Decomposition of CCl4 in Different Atmosphere Thermal Plasmas

    Institute of Scientific and Technical Information of China (English)

    HUANG Jianjun; GUO Wenkang; XU Ping

    2007-01-01

    Decomposition of carbon tetrachloride was studied theoretically in the most commonly used thermal plasma atmosphere such as H2, N2, O2 and water steam. A code developed by the National Aeronautics and Space Administration (NASA) was adopted to calculate the chemical equilibrium distribution and energy consumption of the decomposition of CCl4 in the H2, N2, O2 and water steam atmosphere thermal plasma respectively, with a temperature range of 500 K to 5000 K. In the neutral condition (H2, N2, atmosphere) formation of solid carbon was observed and in the oxygen-atmosphere (O2 and water steam) solid carbon formation disappeared through controlling the ratio of C/O. This indicates that the formation of polycyclic aromatic hydrocarbons (PAHs) is impossible theoretically. The energy consumption in the N2 atmosphere was much higher than that in the H2, O2 and water steam atmosphere at 1500 K.

  9. Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain

    Directory of Open Access Journals (Sweden)

    Zhang Zhi-Jun

    2012-07-01

    Full Text Available Abstract Background Neuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2-chemokine C-C motif receptor 2 (CCR2 signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain. Methods The inferior alveolar nerve and mental nerve transection (IAMNT was used to induce trigeminal neuropathic pain. The expression of ATF3, CCL2, glial fibrillary acidic protein (GFAP, and CCR2 were detected by immunofluorescence histochemical staining and western blot. The cellular localization of CCL2 and CCR2 were examined by immunofluorescence double staining. The effect of a selective CCR2 antagonist, RS504393 on pain hypersensitivity was checked by behavioral testing. Results IAMNT induced persistent (>21 days heat hyperalgesia of the orofacial region and ATF3 expression in the mandibular division of the trigeminal ganglion. Meanwhile, CCL2 expression was increased in the medullary dorsal horn (MDH from 3 days to 21 days after IAMNT. The induced CCL2 was colocalized with astroglial marker GFAP, but not with neuronal marker NeuN or microglial marker OX-42. Astrocytes activation was also found in the MDH and it started at 3 days, peaked at 10 days and maintained at 21 days after IAMNT. In addition, CCR2 was upregulated by IAMNT in the ipsilateral medulla and lasted for more than 21 days. CCR2 was mainly colocalized with NeuN and few cells were colocalized with GFAP. Finally, intracisternal injection of CCR2 antagonist, RS504393 (1, 10 μg significantly attenuated IAMNT-induced heat hyperalgesia. Conclusion The data suggest that CCL2-CCR

  10. MIPAS IMK/IAA CFC-11 (CCl3F) and CFC-12 (CCl2F2) measurements: accuracy, precision and long-term stability

    Science.gov (United States)

    Eckert, E.; Laeng, A.; Lossow, S.; Kellmann, S.; Stiller, G.; von Clarmann, T.; Glatthor, N.; Höpfner, M.; Kiefer, M.; Oelhaf, H.; Orphal, J.; Funke, B.; Grabowski, U.; Haenel, F.; Linden, A.; Wetzel, G.; Woiwode, W.; Bernath, P. F.; Boone, C.; Dutton, G. S.; Elkins, J. W.; Engel, A.; Gille, J. C.; Kolonjari, F.; Sugita, T.; Toon, G. C.; Walker, K. A.

    2016-07-01

    Profiles of CFC-11 (CCl3F) and CFC-12 (CCl2F2) of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) aboard the European satellite Envisat have been retrieved from versions MIPAS/4.61 to MIPAS/4.62 and MIPAS/5.02 to MIPAS/5.06 level-1b data using the scientific level-2 processor run by Karlsruhe Institute of Technology (KIT), Institute of Meteorology and Climate Research (IMK) and Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Astrofísica de Andalucía (IAA). These profiles have been compared to measurements taken by the balloon-borne cryosampler, Mark IV (MkIV) and MIPAS-Balloon (MIPAS-B), the airborne MIPAS-STRatospheric aircraft (MIPAS-STR), the satellite-borne Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS) and the High Resolution Dynamic Limb Sounder (HIRDLS), as well as the ground-based Halocarbon and other Atmospheric Trace Species (HATS) network for the reduced spectral resolution period (RR: January 2005-April 2012) of MIPAS. ACE-FTS, MkIV and HATS also provide measurements during the high spectral resolution period (full resolution, FR: July 2002-March 2004) and were used to validate MIPAS CFC-11 and CFC-12 products during that time, as well as profiles from the Improved Limb Atmospheric Spectrometer, ILAS-II. In general, we find that MIPAS shows slightly higher values for CFC-11 at the lower end of the profiles (below ˜ 15 km) and in a comparison of HATS ground-based data and MIPAS measurements at 3 km below the tropopause. Differences range from approximately 10 to 50 pptv ( ˜ 5-20 %) during the RR period. In general, differences are slightly smaller for the FR period. An indication of a slight high bias at the lower end of the profile exists for CFC-12 as well, but this bias is far less pronounced than for CFC-11 and is not as obvious in the relative differences between MIPAS and any of the comparison instruments. Differences at the lower end of the profile (below ˜ 15 km) and in

  11. Polyphenolic screening and protective properties of some vegetables against CCl4 liver damage

    International Nuclear Information System (INIS)

    In the present study, we screened for the polyphenolic compounds present in some selected tropical vegetables and the protective effect of the vegetable extract against CCl4-induced hepatotoxicity in rats as a way of evaluating their medicinal potential in addition to their nutritional values. The use of HPLC/DAD/MS revealed the presence of some phenolic compounds in the studied vegetables. Crassocephalum crepidioides; caffeoyl derivatives, Talinum triangulare; rutin and kaempferol derivatives, Amaranthus hybridus; caffeoyl derivative, rutin and kaempferol derivative, Hibiscus esculentus; caffeoyl derivative, quercetin derivative and an unidentified flavonoid, Xanthosoma mafaffa; six unidentified flavonoids with similar absorption maximum at different retention times) and Celocia argentia (luteolin derivative and four unidentified flavonoids. Carbon tetrachloride at a dose of 0.5ml/kg body weight (b.w) produced liver damage in rats as manifested by the rise in the levels of ALT (IU/l), AST (IU/l) and total protein (g/l) in the serum (40.60 ± 3.50, 80.60 ± 5.10, 73.20 ± 1.87), in the liver homogenate (1300.00 ± 7.38, 1660.00 ± 13.69, 250.00 ± 7.51) and MDA content (nmol TBARS/mg Liver Protein) in the liver homogenate (82.00 ± 0.02, 82.00 ± 0.07) compared to the control. The result revealed a reduction of the serum marker enzymes (ALT, AST and Total protein), compared with the CCl4 treated group after the administration of the various polyphenolic extract. In a similar manner, the extract brings about a reduction of the MDA content. It could be concluded that the protective properties exhibited by the vegetables could be amongst other factor due to the presence of some polyphenols. (author)

  12. Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.

    Directory of Open Access Journals (Sweden)

    Xiaobao Fan

    Full Text Available Transforming growth factor β1 (TGF-β1 is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 or blocking its signaling pathways is considered to be a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the feasibility of attenuating hepatic fibrosis by vaccination against TGF-β1 with TGF-β1 kinoids. Two TGF-β1 kinoid vaccines were prepared by cross-linking TGF-β1-derived polypeptides (TGF-β1(25-[41-65] and TGF-β1(30-[83-112] to keyhole limpet hemocyanin (KLH. Immunization with the two TGF-β1 kinoids efficiently elicited the production of high-levels of TGF-β1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA and Western blotting. The antisera neutralized TGF-β1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu and attenuated TGF-β1-induced Smad2/3 phosphorylation, α-SMA, collagen type 1 alpha 2 (COL1A2, plasminogen activator inhibitor-1 (PAI-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 expression in the rat hepatic stellate cell (HSC line, HSC-T6. Vaccination against TGF-β1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of α-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-β1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-β1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.

  13. Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1-Infected Individuals

    Science.gov (United States)

    Aziz, Najib; Detels, Roger; Chang, L Cindy; Butch, Anthony W

    2016-01-01

    Objective Uncontrolled HIV infection progresses to the depletion of systemic and mucosal CD4 and AIDS. Early HIV infection may be associated with increases in the concentration of MIP-3α in the blood and gut fluids. MIP-3α/CCL20 is the only chemokine known to interact with CCR6 receptors which are expressed on immature dendritic cells and both effector and memory CD8+ and CD4+ T cells. The role and prognostic value of blood levels of MIP-3α in HIV-infected individuals has yet to be described. Methods We determined the serum levels of MIP-3α, and IFN-γ, in 167 HIV-1-infected and 27 HIV-1-uninfected men participating in the Multicenter AIDS Cohort Study (MACS). The blood biomarkers were measured using enzyme-linked immunosorbent assays (ELISA) and the cell phenotypes using flow cytometry. Results Median serum levels of MIP-3α in HIV-1-infected and uninfected men was significantly different (pabsolute number of CD4+ T cell (p=0.01) and were positively correlated with CD38 molecules on CD8+ T cells (p=0.0002) and with serum levels of IFN-γ (0.006). Conclusion Serum levels of MIP-3α concomitantly increase with plasma levels of IFN-γ, CD38 expression on CD8+ T cells, and decreased of absolute CD4+ T cells in HIV-1-infected men. A higher blood level of MIP-3α may be representation of locally high level of MIP-3α and more recruitment of immature dendritic cell at site of infection. Involvement of CCR6/CCL20 axis and epithelial cells at the recto-colonel level may enhance sexual transmission of HIV-1 in MSM and may be useful as a prognostic marker in HIV-1-infection and AIDS.

  14. HEPATOPROTECTIVE EFFECT OF METHANOLIC EXTRACT OF HEDYOTIS HERBACEA LINN IN CCl4 TREATED MALE RATS

    Directory of Open Access Journals (Sweden)

    Sharma Naveen

    2012-10-01

    Full Text Available To evaluate the hepatoprotective effect of methanolic extract of Hedyotis herbacea Linn in rats treated with CCl4. In Hepatotoxic rats, liver damage was studied by assessing parameters such as aspartate amino transferase (AST, alanine amino transferase (ALT, alkaline phosphate transferase (ALP and gamma glutamyl transpeptidase (GGT in serum and concentration of total proteins, total lipids, phospholipids, triglycerides and cholesterol in both serum and liver. The effect of co-administration of Methanolic extract of Hedyotis herbacea on the above parameters was further investigated. Histopathological study of the liver was also undertaken. A rise in the level of AST, ALT, ALP & GGT in serum evidence as hepatic damage and also changes in other biochemical parameters observed in serum and liver showed a tendency to attain near normalcy in animals co-administration with Methanolic extract of Hedyotis herbacea. The normal value for AST – 25.25 IU/L, ALP – 73.02 IU/L, Protein - 6.62 IU/L, Total lipid – 133.45 gm/100 ml. Were found to alter towards value AST – 34.51 IU/L, ALP – 130.15 IU/L, Protein – 3.42 IU/L, Total lipid – 270.82 gm/100 ml in Hepatoprotective rats. These parameters attained near normal values. AST – 24.82 IU/L, ALP – 85.15 IU/L, Protein – 5.98 IU/L, Total lipid – 151.24 gm/100 ml in Methanolic extract of Hedyotis herbacea co-administrated rats. Profound steatosis- Ballooning degeneration and nodule formation observed in the hepatic architecture of CCl4 treated rats were found to acquire near normalcy in drug co-administration rats thus corroborating the biochemical observations. The study substantiates the Hepatoprotective potential of Methanolic extract of Hedyotis herbacea.

  15. Effect of Yiguanjian decoction on cell differentiation and proliferation in CCl4-treated mice

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ling Wang; Dong-Wei Jia; Hui-Yang Liu; Xiao-Feng Yan; Ting-Jie Ye; Xu-Dong Hu; Bo-Qin Li

    2012-01-01

    AIM:To investigate the cellular mechanisms of action of Yiguanjian (YGJ) decoction in treatment of chronic hepatic injury.METHODS:One group of mice was irradiated,and received enhanced green fluorescent protein (EGFP)-positive bone marrow transplants followed by 13 wk of CCl4 injection and 6 wk of oral YGJ administration.A second group of Institute for Cancer Research mice was treated with 13 wk of CCl4 injection and 6 wk of oral YGJ administration.Liver function,histological changes in the liver,and Hyp content were analyzed.The expression of α-smooth muscle actin (α-SMA),F4/80,albumin (Alb),EGFP,mitogen-activated protein kinase-2 (PKM2),Ki-67,α fetoprotein (AFP),monocyte chemotaxis protein-1 and CC chemokine receptor 2 were assayed.RESULTS:As hepatic damage progressed,EGFP-positive marrow cells migrated into the liver and were mainly distributed along the fibrous septa.They showed a conspicuous coexpression of EGFP with α-SMA and F4/80 but no coexpression with AIb.Moreover,the expression of PKM2,AFP and Ki-67 was enhanced dynamically and steadily over the course of liver injury.YGJ abrogated the increases in the number of bone marrow-derived fibrogenic cells in the liver,inhibited expression of both progenitor and mature hepatocyte markers,and reduced fibrogenesis.CONCLUSION:YGJ decoction improves liver fibrosis by inhibiting the migration of bone marrow cells into the liver as well as inhibiting their differentiation and suppressing the proliferation of both progenitors and hepatocytes in the injured liver.

  16. Age- and light-dependent development of localised retinal atrophy in CCL2(-/-CX3CR1(GFP/GFP mice.

    Directory of Open Access Journals (Sweden)

    Mei Chen

    Full Text Available Previous studies have shown that CCL2/CX3CR1 deficient mice on C57BL/6N background (with rd8 mutation have an early onset (6 weeks of spontaneous retinal degeneration. In this study, we generated CCL2(-/-CX3CR1(GFP/GFP mice on the C57BL/6J background. Retinal degeneration was not detected in CCL2(-/-CX3CR1(GFP/GFP mice younger than 6 months. Patches of whitish/yellowish fundus lesions were observed in 17∼60% of 12-month, and 30∼100% of 18-month CCL2(-/-CX3CR1(GFP/GFP mice. Fluorescein angiography revealed no choroidal neovascularisation in these mice. Patches of retinal pigment epithelium (RPE and photoreceptor damage were detected in 30% and 50% of 12- and 18-month CCL2(-/-CX3CR1(GFP/GFP mice respectively, but not in wild-type mice. All CCL2(-/-CX3CR1(GFP/GFP mice exposed to extra-light (∼800lux, 6 h/day, 6 months developed patches of retinal atrophy, and only 20-25% of WT mice which underwent the same light treatment developed atrophic lesions. In addition, synaptophysin expression was detected in the outer nucler layer (ONL of area related to photoreceptor loss in CCL2(-/-CX3CR1(GFP/GFP mice. Markedly increased rhodopsin but reduced cone arrestin expression was observed in retinal outer layers in aged CCL2(-/-CX3CR1(GFP/GFP mice. GABA expression was reduced in the inner retina of aged CCL2(-/-CX3CR1(GFP/GFP mice. Significantly increased Müller glial and microglial activation was observed in CCL2(-/-CX3CR1(GFP/GFP mice compared to age-matched WT mice. Macrophages from CCL2(-/-CX3CR1(GFP/GFP mice were less phagocytic, but expressed higher levels of iNOS, IL-1β, IL-12 and TNF-α under hypoxia conditions. Our results suggest that the deletions of CCL2 and CX3CR1 predispose mice to age- and light-mediated retinal damage. The CCL2/CX3CR1 deficient mouse may thus serve as a model for age-related atrophic degeneration of the RPE, including the dry type of macular degeneration, geographic atrophy.

  17. Inhibitory effects of saikosaponin-d on CCl4-induced hepatic fibrogenesis in rats

    Institute of Scientific and Technical Information of China (English)

    Shuang-Suo Dang; Bao-Feng Wang; Yan-An Cheng; Ping Song; Zhen-Guo Liu; Zong-Fang Li

    2007-01-01

    AIM: To investigate the suppressive effect of saikosaponin-d (SSd) on hepatic fibrosis in rats induced by CCl4 injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-κB (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukins-6 (IL-6).METHODS: Hepatic fibrosis models were induced by subcutaneous injection of CCl4 at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses (1.0,1.5 and 2.0 mg/kg) once daily for 6 wk in combination with CCl4, while the control group received olive oil instead of CCl4. At the end of the experiment, rats were anesthetized and killed (except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in lowdose group). Hematoxylin and eosin (HE) staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase (ALT), triglyeride (TG), albumin (ALB), globulin (GLB),hyaluronic acid (HA) and laminin (LN) in serum and the content of hydroxyproline (HYP) in liver were measured by biochemical examinations and radioimmuneoassay,respectively. In addition, the expression of TNF-α and IL-6 in liver homogenate was evaluated by enzymelinked immunosorbent assay (ELISA) and the levels of NF-κBp65 and I-κBα in liver tissue were analyzed by Western blotting.RESULTS: Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-α and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas,the treatment with SSd markedly reduced all the above parameters compared with the model group, especially in the medium group (ALT: 412 ± 94

  18. Fast food diet with CCl4 micro-dose induced hepatic-fibrosis –a novel animal model

    Science.gov (United States)

    2014-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is defined as a spectrum of conditions ranging from hepatocellular steatosis to steatohepatitis and fibrosis, progressing to cirrhosis, which occur in the absence of excessive alcohol use. Several animal models capture aspects of NAFLD but are limited either in their representation of the disease stages or use for development of therapeutics due to the extended periods of time required to develop full histological features. Methods Here, we report the development of a novel rat model for NAFLD that addresses some of these limitations. We used a fast food diet (FFD) and a CCl4 micro dose (0.5 ml/kg B.wt) for 8 weeks in Wistar rats. Serological analyses, gene expression profiling and liver histology studies were conducted to investigate the development of steatosis, steatohepatitis and fibrosis in the FFD-CCl4 model when compared to the individual effects of a FFD or a micro dose of CCl4 in rats. Results The serum biochemical profile of the FFD-CCl4 model showed an increase in liver injury and fibrosis. This was also accompanied by a significant increase in liver triglycerides (TG), inflammation and oxidative stress. Importantly, we observed extensive fibrosis confirmed by: i) increased gene expression of fibrosis markers and, ii) moderate to severe collagen deposition seen as perisinusoidal and bridging fibrosis using H&E, Trichome and Sirius Red staining. Conclusions In summary, we find that the FFD-CCl4 rat model developed NAFLD histological features including, steatosis, inflammation and fibrosis in 8 weeks showing promise as a model that can be used to develop NAFLD therapeutics and liver anti-fibrotics. PMID:24884574

  19. Amniotic fluid stem cells inhibit the progression of bleomycin-induced pulmonary fibrosis via CCL2 modulation in bronchoalveolar lavage.

    Directory of Open Access Journals (Sweden)

    Orquidea Garcia

    Full Text Available The potential for amniotic fluid stem cell (AFSC treatment to inhibit the progression of fibrotic lung injury has not been described. We have previously demonstrated that AFSC can attenuate both acute and chronic-fibrotic kidney injury through modification of the cytokine environment. Fibrotic lung injury, such as in Idiopathic Pulmonary Fibrosis (IPF, is mediated through pro-fibrotic and pro-inflammatory cytokine activity. Thus, we hypothesized that AFSC treatment might inhibit the progression of bleomycin-induced pulmonary fibrosis through cytokine modulation. In particular, we aimed to investigate the effect of AFSC treatment on the modulation of the pro-fibrotic cytokine CCL2, which is increased in human IPF patients and is correlated with poor prognoses, advanced disease states and worse fibrotic outcomes. The impacts of intravenous murine AFSC given at acute (day 0 or chronic (day 14 intervention time-points after bleomycin injury were analyzed at either day 3 or day 28 post-injury. Murine AFSC treatment at either day 0 or day 14 post-bleomycin injury significantly inhibited collagen deposition and preserved pulmonary function. CCL2 expression increased in bleomycin-injured bronchoalveolar lavage (BAL, but significantly decreased following AFSC treatment at either day 0 or at day 14. AFSC were observed to localize within fibrotic lesions in the lung, showing preferential targeting of AFSC to the area of fibrosis. We also observed that MMP-2 was transiently increased in BAL following AFSC treatment. Increased MMP-2 activity was further associated with cleavage of CCL2, rendering it a putative antagonist for CCL2/CCR2 signaling, which we surmise is a potential mechanism for CCL2 reduction in BAL following AFSC treatment. Based on this data, we concluded that AFSC have the potential to inhibit the development or progression of fibrosis in a bleomycin injury model during both acute and chronic remodeling events.

  20. Chemokine CCL2 up-regulated in the medullary dorsal horn astrocytes contributes to nocifensive behaviors induced by experimental tooth movement.

    Science.gov (United States)

    Luo, Wei; Fu, Runqing; Tan, Yu; Fang, Bing; Yang, Zhi

    2014-02-01

    To test the hypothesis that the astrocytic chemokine (C-C motif) ligand 2 (CCL2) plays an important role in nocifensive behaviors after experimental tooth movement (ETM), the expression and cellular localization of CCL2 and astrocyte activation in the medullary dorsal horn (MDH) were determined by immunohistochemistry in rats. The dose-dependent effects of intrathecal C-C chemokine receptor type 2 (CCR2) antagonists on these changes in nocifensive behaviors were evaluated. Exogenous CCL2 was added to medullary dorsal horn slices to evaluate its contributory role in the induction of extracellular signal-regulated kinase (ERK) activation ex vivo. We found a significant increase in the expression of CCL2 and glial fibrillary acidic protein (GFAP), corresponding well to the nocifensive behaviors after ETM. In addition, application of recombinant CCL2 led to ERK activation, which could be attenuated effectively by pretreatment with CCL2-neutralizing antibody ex vivo. The magnitude of the nocifensive behavior could be reduced by medullary CCR2 antagonists in a dose-dependent manner. Therefore, the astrocytic CCL2 is actively involved in the development and maintenance of tooth-movement pain and thus may be a potential target for analgesics in orthodontic nocifensive responses control.

  1. Regulation of CCL2 expression by an upstream TALE homeodomain protein-binding site that synergizes with the site created by the A-2578G SNP.

    Science.gov (United States)

    Page, Stephen H; Wright, Edward K; Gama, Lucio; Clements, Janice E

    2011-01-01

    CC Chemokine Ligand 2 (CCL2) is a potent chemoattractant produced by macrophages and activated astrocytes during periods of inflammation within the central nervous system. Increased CCL2 expression is correlated with disease progression and severity, as observed in pulmonary tuberculosis, HCV-related liver disease, and HIV-associated dementia. The CCL2 distal promoter contains an A/G polymorphism at position -2578 and the homozygous -2578 G/G genotype is associated with increased CCL2 production and inflammation. However, the mechanisms that contribute to the phenotypic differences in CCL2 expression are poorly understood. We previously demonstrated that the -2578 G polymorphism creates a TALE homeodomain protein binding site (TALE binding site) for PREP1/PBX2 transcription factors. In this study, we identified the presence of an additional TALE binding site 22 bp upstream of the site created by the -2578 G polymorphism and demonstrated the synergistic effects of the two sites on the activation of the CCL2 promoter. Using chromatin immunoprecipitation (ChIP) assays, we demonstrated increased binding of the TALE proteins PREP1 and PBX2 to the -2578 G allele, and binding of IRF1 to both the A and G alleles. The presence of TALE binding sites that form inverted repeats within the -2578 G allele results in increased transcriptional activation of the CCL2 distal promoter while the presence of only the upstream TALE binding site within the -2578 A allele exerts repression of promoter activity.

  2. C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.

    Science.gov (United States)

    Denis, Catherine; Deiteren, Kathleen; Mortier, Anneleen; Tounsi, Amel; Fransen, Erik; Proost, Paul; Renauld, Jean-Christophe; Lambeir, Anne-Marie

    2012-01-01

    Carboxypeptidase M (CPM) targets the basic amino acids arginine and lysine present at the C-terminus of peptides or proteins. CPM is thought to be involved in inflammatory processes. This is corroborated by CPM-mediated trimming and modulation of inflammatory factors, and expression of the protease in inflammatory environments. Since the function of CPM in and beyond inflammation remains mainly undefined, the identification of natural substrates can aid in discovering the (patho)physiological role of CPM. CCL1/I-309, with its three C-terminal basic amino acids, forms a potential natural substrate for CPM. CCL1 plays a role not only in inflammation but also in apoptosis, angiogenesis and tumor biology. Enzymatic processing differently impacts the biological activity of chemokines thereby contributing to the complex regulation of the chemokine system. The aim of the present study was to investigate whether (i) CCL1/I-309 is prone to trimming by CPM, and (ii) the biological activity of CCL1 is altered after C-terminal proteolytic processing. CCL1 was identified as a novel substrate for CPM in vitro using mass spectrometry. C-terminal clipping of CCL1 augmented intracellular calcium release mediated by CCR8 but reduced the binding of CCL1 to CCR8. In line with the higher intracellular calcium release, a pronounced increase of the anti-apoptotic activity of CCL1 was observed in the BW5147 cellular model. CCR8 signaling, CCR8 binding and anti-apoptotic activity were unaffected when CPM was exposed to the carboxypeptidase inhibitor DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid. The results of this study suggest that CPM is a likely candidate for the regulation of biological processes relying on the CCL1-CCR8 system. PMID:22479563

  3. Regulation of the CCL2 gene in pancreatic β-cells by IL-1β and glucocorticoids: role of MKP-1.

    Directory of Open Access Journals (Sweden)

    Susan J Burke

    Full Text Available Release of pro-inflammatory cytokines from both resident and invading leukocytes within the pancreatic islets impacts the development of Type 1 diabetes mellitus. Synthesis and secretion of the chemokine CCL2 from pancreatic β-cells in response to pro-inflammatory signaling pathways influences immune cell recruitment into the pancreatic islets. Therefore, we investigated the positive and negative regulatory components controlling expression of the CCL2 gene using isolated rat islets and INS-1-derived β-cell lines. We discovered that activation of the CCL2 gene by IL-1β required the p65 subunit of NF-κB and was dependent on genomic response elements located in the -3.6 kb region of the proximal gene promoter. CCL2 gene transcription in response to IL-1β was blocked by pharmacological inhibition of the IKKβ and p38 MAPK pathways. The IL-1β-mediated increase in CCL2 secretion was also impaired by p38 MAPK inhibition and by glucocorticoids. Moreover, multiple synthetic glucocorticoids inhibited the IL-1β-stimulated induction of the CCL2 gene. Induction of the MAP Kinase Phosphatase-1 (MKP-1 gene by glucocorticoids or by adenoviral-mediated overexpression decreased p38 MAPK phosphorylation, which diminished CCL2 gene expression, promoter activity, and release of CCL2 protein. We conclude that glucocorticoid-mediated repression of IL-1β-induced CCL2 gene transcription and protein secretion occurs in part through the upregulation of the MKP-1 gene and subsequent deactivation of the p38 MAPK. Furthermore, the anti-inflammatory actions observed with MKP-1 overexpression were obtained without suppressing glucose-stimulated insulin secretion. Thus, MKP-1 is a possible target for anti-inflammatory therapeutic intervention with preservation of β-cell function.

  4. Protective effect of selenium-enriched lactobacillus on CCl4-induced liver injury in mice and its possible mechanisms

    Institute of Scientific and Technical Information of China (English)

    Long Chen; Dao-Dong Pan; Juan Zhou; Ying-Zi Jiang

    2005-01-01

    AIM: To study the protective effects and mechanisms of Se-enriched lactobacillus on liver injury caused by carbon tetrachloride (CCl4) in mice.MWTHODS: Seventy-two ICR mice were randomly divided into four groups: normal group, CCl4-induced model group,low Se-enriched lactobacillus treatment group (L-Se group),and high Se-enriched lactobacillus treatment group (H-Se group). During a 3-wk experimental period, the common complete diet was orally provided daily for normal group and model group, and the mice in L-Se and H-Se groups were given a diet with 2 and 4 mg of organoselenium from Se-enriched lactobacillus per kg feed, respectively. From the 2nd wk of experiment, the model group, L-Se group,and H-Se group received abdominal cavity injection of olive oil solution containing 500 mL/L CCl4 (0.07 mL/100 g body mass) to induce liver injury, and the normal group was given olive oil on every other day for over 2 wk. In the first 2 wk post injection with CCl4, mice in each group were killed. The specimens of blood, liver tissue, and macrophages in abdominal cavity fluid were taken. Then the activities of the following liver tissue injury-associated enzymes including glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as malondialdehyde (MDA) content were assayed. Changes of phagocytic rate and phagocytic index in macrophages were observed with Wright-Giemsa stain. Plasma TNF-α level was measured by radioimmunoassay. The level of intracellular free Ca2+ ([Ca2+]i) in hepatocytes was detected under a laser scanning confocal microscope.RESULTS: During the entire experimental period, the AST and ALT activities in liver were greatly enhanced by CCl4 and completely blunted by both low and high doses of Se-enriched lactobacillus. The Se-enriched lactobacillus-protected liver homogenate GSH-Px and SOD activities were higher or significantly higher than those in model group and were close to

  5. Hepatocurative potential of Vitex doniana root bark, stem bark and leaves extracts against CCl4-induced liver damage in rats

    Institute of Scientific and Technical Information of China (English)

    James Dorcas Bolanle; Kadejo Olubukola Adetoro; Sallau Abdullahi Balarabe; Owolabi Olumuyiwa Adeyemi

    2014-01-01

    Objective: To evaluate the hepatocurative effects of aqueous root bark, stem bark and leaves ofVitex doniana in carbon tetrachloride (CCl albino rats.Methods:4) induced liver damage and non induced liver damage were assigned into liver damage and non liver damage groups of 6 rats in a group. The animals in the CCl4 induced liver damage groups, were induced by intraperitoneal injection with a single dose of CCl4 (1 mL/kg body weight) as a 1:1(v/v) solution in olive oil and were fasted for 36 h before the subsequent treatment with aqueous root bark, stem bark and leaves extracts of Vitex doniana and vitamin E as standard drug (100 mg/kg body weight per day) for 21 d, while the animals in the non induced groups were only treated with the daily oral administration of these extracts at the same dose. The administration of CCl4 was done once a week for a period of 3 weeks.Results:There was significant (P<0.05) increase in concentration of all liver marker enzymes, A total of 60 albino rats (36 induced liver damage and 24 non induced liver damage) alanine aminotransferase, aspartate aminotransferase and alkaline aminotransferase (ALT, AST and ALP) and significant (P<0.05) decrease in albumin in the CCl4 induced liver damage control when compared to the normal control. The extracts caused a significant (P<0.05) reduction in the serum activities of liver marker enzymes (ALT, AST and ALP) and a significant (P<0.05) increase in albumin of all the induced treated groups. Only stem bark extract and vitamin E significantly (P<0.05) increased total protein. All the extracts significantly (P<0.05) lowered serum creatinine whereas only root bark extract significantly (P<0.05) lowered serum level of urea in the rats with CCl4 induced liver damage.Conclusion:Hepatocurative study shows that all the plant parts (root bark, stem bark and leaves) possess significant hepatocurative properties among other therapeutic values justifying their use in folklore medicine.

  6. Administration of Myelin Basic Protein Peptides Encapsulated in Mannosylated Liposomes Normalizes Level of Serum TNF-α and IL-2 and Chemoattractants CCL2 and CCL4 in Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Yakov Lomakin

    2016-01-01

    Full Text Available We have previously shown that immunodominant MBP peptides encapsulated in mannosylated liposomes (Xemys effectively suppressed experimental allergic encephalomyelitis (EAE. Within the frames of the successfully completed phase I clinical trial, we investigated changes in the serum cytokine profile after Xemys administration in MS patients. We observed a statistically significant decrease of MCP-1/CCL2, MIP-1β/CCL4, IL-7, and IL-2 at the time of study completion. In contrast, the serum levels of TNF-α were remarkably elevated. Our data suggest that the administration of Xemys leads to a normalization of cytokine status in MS patients to values commonly reported for healthy subjects. These data are an important contribution for the upcoming Xemys clinical trials.

  7. Insulin Resistance, Inflammation, and Obesity: Role of Monocyte Chemoattractant Protein-1 (orCCL2 in the Regulation of Metabolism

    Directory of Open Access Journals (Sweden)

    Anna Rull

    2010-01-01

    Full Text Available To maintain homeostasis under diverse metabolic conditions, it is necessary to coordinate nutrient-sensing pathways with the immune response. This coordination requires a complex relationship between cells, hormones, and cytokines in which inflammatory and metabolic pathways are convergent at multiple levels. Recruitment of macrophages to metabolically compromised tissue is a primary event in which chemokines play a crucial role. However, chemokines may also transmit cell signals that generate multiple responses, most unrelated to chemotaxis, that are involved in different biological processes. We have reviewed the evidence showing that monocyte chemoattractant protein-1 (MCP-1 or CCL2 may have a systemic role in the regulation of metabolism that sometimes is not necessarily linked to the traffic of inflammatory cells to susceptible tissues. Main topics cover the relationship between MCP-1/CCL2, insulin resistance, inflammation, obesity, and related metabolic disturbances.

  8. NF-kappaB-driven STAT2 and CCL2 expression in astrocytes in response to brain injury

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Babcock, Alicia A; Owens, Trevor

    2008-01-01

    induces glial response. Astrocytes are the major glial population in the CNS. We examined expression of STATs and the chemokine CCL2 and their relationship to astroglial NF-kappaB signaling in the CNS following axonal transection. Double labeling with Mac-1/CD11b and glial fibrillary acidic protein...... revealed that STAT2 up-regulation and phosphorylation colocalized exclusively to astrocytes, suggesting the involvement of STAT2 activating signals selectively in astroglial response to injury. STAT1 was also up-regulated and phosphorylated but not exclusively in astrocytes. Both STAT2 up-regulation and...... phosphorylation were NF-kappaB -dependent since they did not occur in the lesion-reactive hippocampus of transgenic mice with specific inhibition of NF-kappaB activation in astrocytes. We further showed that lack of NF-kappaB signaling significantly reduced injury-induced CCL2 expression as well as leukocyte...

  9. Direct and indirect pharmacological modulation of CCL2/CCR2 pathway results in attenuation of neuropathic pain - In vivo and in vitro evidence.

    Science.gov (United States)

    Piotrowska, Anna; Kwiatkowski, Klaudia; Rojewska, Ewelina; Slusarczyk, Joanna; Makuch, Wioletta; Basta-Kaim, Agnieszka; Przewlocka, Barbara; Mika, Joanna

    2016-08-15

    The repeated administration of microglial inhibitor (minocycline) and CCR2 antagonist (RS504393) attenuated the neuropathic pain symptoms in rats following chronic constriction injury of the sciatic nerve, which was associated with decreased spinal microglia activation and the protein level of CCL2 and CCR2. Furthermore, in microglia primary cell cultures minocycline downregulated both CCL2 and CCR2 protein levels after lipopolysaccharide-stimulation. Additionally, in astroglia primary cell cultures minocycline decreased the expression of CCL2, but not CCR2. Our results provide new evidence that modulation of CCL2/CCR2 pathway by microglial inhibitor as well as CCR2 antagonist is effective for neuropathic pain development in rats. PMID:27397071

  10. Tag SNP polymorphism of CCL2 and its role in clinical tuberculosis in Han Chinese pediatric population.

    Directory of Open Access Journals (Sweden)

    Wei-Xing Feng

    Full Text Available BACKGROUND: Chemokine (C-C motif ligand 2 CCL2/MCP-1 is among the key signaling molecules of innate immunity; in particular, it is involved in recruitment of mononuclear and other cells in response to infection, including tuberculosis (TB and is essential for granuloma formation. METHODOLOGY/PRINCIPAL FINDINGS: We identified a tag SNP for the CCL2/MCP-1 gene (rs4586 C/T. In order to understand whether this SNP may serve to evaluate the contribution of the CCL2 gene to the expression of TB disease, we further analysed distribution of its alleles and genotypes in 301 TB cases versus 338 non-infected controls (all BCG vaccinated representing a high-risk pediatric population of North China. In the male TB subgroup, the C allele was identified in a higher rate (P = 0.045, and, acting dominantly, was found to be a risk factor for clinical TB (P = 0.029. Homozygous TT genotype was significantly associated with lower CSF mononuclear leukocyte (ML counts in patients with tuberculous meningitis (TBM (P = 0.001. CONCLUSIONS/SIGNIFICANCE: The present study found an association of the CCL2 tag SNP rs4586 C allele and pediatric TB disease in males, suggesting that gender may affect the susceptibility to TB even in children. The association of homozygous TT genotype with decreased CSF mononuclear leukocyte (ML count not only suggests a clinical significance of this SNP, but indicates its potential to assist in the clinical assessment of suspected TBM, where delay is critical and diagnosis is difficult.

  11. Hepatoprotective effect of flavonol glycosides rich fraction from Egyptian Vicia calcarata Desf. against CCl4-induced liver damage in rats.

    Science.gov (United States)

    Singab, Abdel Nasser B; Youssef, Diaa T A; Noaman, Eman; Kotb, Saeed

    2005-07-01

    The hepatoprotective activity of flavonol glycosides rich fraction (F-2), prepared from 70% alcohol extract of the aerial parts of V. calcarata Desf., was evaluated in a rat model with a liver injury induced by daily oral administration of CCl4 (100 mg/kg, b.w) for four weeks. Treatment of the animals with F-2 using a dose of (25 mg/kg, b.w) during the induction of hepatic damage by CCl4 significantly reduced the indices of liver injuries. The hepatoprotective effects of F-2 significantly reduced the elevated levels of the following serum enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The antioxidant activity of F-2 markedly ameliorated the antioxidant parameters including glutathione (GSH) content, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), plasma catalase (CAT) and packed erythrocytes glucose-6-phosphate dehydrogenase (G6PDH) to be comparable with normal control levels. In addition, it normalized liver malondialdehyde (MDA) levels and creatinine concentration. Chromatographic purification of F-2 resulted in the isolation of two flavonol glycosides that rarely occur in the plant kingdom, identified as quercetin-3, 5-di-O-beta-D-diglucoside (5) and kaempferol-3, 5-di-O-beta-D-diglucoside (4) in addition to the three known compounds identified as quercetin-3-O-alpha-L-rhamnosyl- (1-->6)-beta-D-glucoside [rutin, 3], quercetin-3-O-beta-D-glucoside [isoquercitrin, 2] and kaempferol-3-O-beta-D-glucoside [astragalin, 1]. These compounds were identified based on interpretation of their physical, chemical, and spectral data. Moreover, the spectrophotometric estimation of the flavonoids content revealed that the aerial parts of the plant contain an appreciable amount of flavonoids (0.89%) calculated as rutin. The data obtained from this study revealed that the flavonol glycosides of F-2 protect the rat liver from hepatic damage induced by CCl4 through inhibition of

  12. Effect of compound rhodiola sachalinensis A Bor on CCl4-induced liver fibrosis in rats and its probable molecular mechanisms

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ling Wu; Wei-Zheng Zeng; Pi-Long Wang; Chun-Tao Lei; Ming-De Jiang; Xiao-Bin Chen; Yong Zhang; Hui Xu; Zhao Wang

    2003-01-01

    AIM: To explore the anti-fibrotic effect of a traditional Chinese medicine, compound rhodiola sachalinensis A Bor on CCl4-induced liver fibrosis in rats and its probable molecular mechanisms.METHODS: Ninety healthy male SD rats were randomly divided into three groups: normal group (n=10), treatment group of compound rhodiola sachalinensis A Bor (n=40) and CCl4-induced model group (n=40). The liver fibrosis was induced by CCl4 subcutaneous injection. Treatment group was administered with compound rhodiola sachalinensis A Bor (0.5 g/kg) once a day at the same time. Then the activities of several serum fibrosis-associated enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST),N-acetyl-beta-D-glucosaminidase (β-NAG) and the levels of serum procollagen Ⅲ (PCⅢ), collagen IV (CIV), hyaluronic acid (HA) were assayed. The histopathological changes were observed with HE, VG and Masson stain. The expression of TGF-β1 mRNA, α1 (I) mRNA and Na+/Ca2+ exchanger (NCX)mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR) in situ.RESULTS: Compound rhodiola sachalinensis A Bor significantly reduced serum activities of ALT, AST, β-NAG and decreased the levels of PCⅢ, CIV, HA, improved the liver histopathological changes, inhibited the expression of TGFβ1 mRNA, α(I) mRNA and Na+/Ca2+ exchanger mRNA in rats.CONCLUSION: Compound rhodiola sachalinensis A Bor can intervene in CCl4-induced liver fibrosis in rats, in which potential mechanisms may be decreasing the production of TGF-β1, reducing the production of collagen, preventing the activation of hepatic stellate cell (HSC) and inhibiting the expression of TGF-β1 mRNA, α1(I) mRNA and Na+/Ca2+exchanger mRNA.

  13. Effect of aqueous extract of Tinospora cordifolia on functions of peritoneal macrophages isolated from CCl4 intoxicated male albino mice

    OpenAIRE

    Sharma Gauri D; Sengupta Mahuya; Chakraborty Biswajit

    2011-01-01

    Abstract Background The current practice of ingesting phytochemicals for supporting the immune system or fighting infections is based on centuries-old tradition. Macrophages are involved at all the stages of an immune response. The present study focuses on the immunostimulant properties of Tinospora cordifolia extract that are exerted on circulating macrophages isolated from CCl4 (0.5 ml/kg body weight) intoxicated male albino mice. Methods Apart from damaging the liver system, carbon tetrach...

  14. Inhibition of chemokine (C-C motif receptor 7 sialylation suppresses CCL19-stimulated proliferation, invasion and anti-anoikis.

    Directory of Open Access Journals (Sweden)

    Mei-Lin Su

    Full Text Available Chemokine (C-C motif receptor 7 (CCR7 is involved in lymph-node homing of naive and regulatory T cells and lymphatic metastasis of cancer cells. Sialic acids comprise a group of monosaccharide units that are added to the terminal position of the oligosaccharide chain of glycoproteins by sialyation. Recent studies suggest that aberrant sialylation of receptor proteins contributes to proliferation, motility, and drug resistance of cancer cells. In this study, we addressed whether CCR7 is a sialylated receptor protein and tried to elucidate the effect of sialylation in the regulation of signal transduction and biological function of CCR7. Our results demonstrated that α-2, 3-sialyltransferase which catalyze sialylation reaction in vivo was overexpressed in breast tumor tissues and cell lines. Lectin blot analysis clearly demonstrated that CCR7 receptor was sialyated in breast cancer cells. Chemokine (C-C motif ligand 19 (CCL19, the cognate ligand for CCR7, induced the activation of extracellular signal-regulated kinase (ERK and AKT signaling and increased the expression of cell cycle regulatory proteins and proliferation of breast cancer cells. When cells were pre-treated with a sialyltransferase inhibitor AL10 or sialidase, CCL19-induced cell growth was significantly suppressed. CCL19 also increased invasion and prevented anoikis by up-regulating pro-survival proteins Bcl-2 and Bcl-xL. Inhibition of sialylation by AL10 totally abolished these effects. Finally, we showed that AL10 inhibited tumorigenicity of breast cancer in experimental animals. Taken together, we demonstrate for the first time that CCR7 receptor is a sialylated protein and sialylation is important for the paracrine stimulation by its endogenous ligand CCL19. In addition, inhibition of aberrant sialylation of CCR7 suppresses proliferation and invasion and triggers anoikis in breast cancer cells. Targeting of sialylation enzymes may be a novel strategy for breast cancer treatment.

  15. MicroRNA-200c Represses IL-6, IL-8, and CCL-5 Expression and Enhances Osteogenic Differentiation

    Science.gov (United States)

    Sharp, Thad; Khorsand, Behnoush; Fischer, Carol; Eliason, Steven; Salem, Ali; Akkouch, Adil; Brogden, Kim; Amendt, Brad A.

    2016-01-01

    MicroRNAs (miRs) regulate inflammation and BMP antagonists, thus they have potential uses as therapeutic reagents. However, the molecular function of miR-200c in modulating proinflammatory and bone metabolic mediators and osteogenic differentiation is not known. After miR-200c was transduced into a human embryonic palatal mesenchyme (HEPM) (a cell line of preosteoblasts), using lentiviral vectors, the resulting miR-200c overexpression increased osteogenic differentiation biomarkers, including osteocalcin (OCN) transcripts and calcium content. miR-200c expression also down-regulated interleukin (IL)-6, IL-8, and chemokine (C-C motif) ligand (CCL)-5 under lipopolysaccharide (LPS) stimulation and increased osteoprotegerin (OPG) in these cells. miR-200c directly regulates the expression of IL-6, IL-8 and CCL-5 transcripts by binding to their 3’UTRs. A plasmid-based miR-200c inhibitor effectively reduces their binding activities. Additionally, miR-200c delivered using polyethylenimine (PEI) nanoparticles effectively inhibits IL-6, IL-8 and CCL-5 in primary human periodontal ligament fibroblasts and increases the biomarkers of osteogenic differentiation in human bone marrow mesenchymal stem cells (MSCs), including calcium content, ALP, and Runx2. These data demonstrate that miR-200c represses IL-6, IL-8 and CCL-5 and improves osteogenic differentiation. miR-200c may potentially be used as an effective means to prevent periodontitis-associated bone loss by arresting inflammation and osteoclastogenesis and enhancing bone regeneration. PMID:27529418

  16. Oligonol Ameliorates CCl4-Induced Liver Injury in Rats via the NF-Kappa B and MAPK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Jeonghyeon Bak

    2016-01-01

    Full Text Available Oxidative stress is thought to be a key risk factor in the development of hepatic diseases. Blocking or retarding the reactions of oxidation and the inflammatory process by antioxidants could be a promising therapeutic intervention for prevention or treatment of liver injuries. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from lychee fruit. In this study, we investigated the anti-inflammatory effect of oligonol on carbon tetrachloride- (CCl4- induced acute hepatic injury in rats. Oral administration of oligonol (10 or 50 mg/kg reduced CCl4-induced abnormalities in liver histology and serum AST and serum ALT levels. Oligonol treatment attenuated the CCl4-induced production of inflammatory mediators, including TNF-α, IL-1β, cyclooxygenase-2 (COX-2, and inducible nitric oxide synthase (iNOS mRNA levels. Western blot analysis showed that oligonol suppressed proinflammatory nuclear factor-kappa B (NF-κB p65 activation, phosphorylation of extracellular signal-regulated kinase (ERK, c-Jun NH2-terminal kinase (JNK, and p38 mitogen-activated protein kinases (MAPKs as well as Akt. Oligonol exhibited strong antioxidative activity in vitro and in vivo, and hepatoprotective activity against t-butyl hydroperoxide-induced HepG2 cells. Taken together, oligonol showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream kinases including MAPKs and Akt.

  17. Hepatoprotective and Antioxidant Effect of Hibiscus Polyphenol Rich Extract (HPE) Against Carbon Tetrachloride (CCL4) - Induced Damage in Rats

    OpenAIRE

    Adetutu, Adewale; Owoade, Abiodun O.

    2013-01-01

    Aims: Hibiscus sabdariffa is a medicinal plant that is consumed for its health benefits in Africa. The study was designed to investigate the hepatoprotective potentials of Hibiscus polyphenolic rich extract (HPE), (a group of phenolic compounds occurring in the dried calyx of Hibiscus sabdariffa) against CCl4-induced damaged in rats. Place and Duration of Study: Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomosho, Nigeria, between January 2011 and June 2012. Method...

  18. Re-evaluation of the lifetimes of the major CFCs and CH3CCl3 using atmospheric trends

    Directory of Open Access Journals (Sweden)

    J. W. Elkins

    2012-09-01

    Full Text Available Since the Montreal Protocol on substances that deplete the ozone layer and its amendments came into effect, growth rates of the major ozone depleting substances (ODS, particularly CFC-11, -12 and -113 and CH3CCl3, have declined markedly, paving the way for global stratospheric ozone recovery. Emissions have now fallen to relatively low levels, therefore the rate at which this recovery occurs will depend largely on the atmospheric lifetime of these compounds. The first ODS measurements began in the early 1970s along with the first lifetime estimates calculated by considering their atmospheric trends. We now have global mole fraction records spanning multiple decades, prompting this lifetime re-evaluation. Using surface measurements from the Advanced Global Atmospheric Gases Experiment (AGAGE and the National Oceanic and Atmospheric Administration Global Monitoring Division (NOAA GMD from 1978 to 2011, we estimated the lifetime of CFC-11, CFC-12, CFC-113 and CH3CCl3 using a multi-species inverse method. The CFC-11 lifetime of 45 yr, currently recommended in the World Meteorological Organisation (WMO Scientific Assessment of Ozone Depletion, lies at the lower uncertainty bound of our estimates which are 524066 yr (1-sigma uncertainty when AGAGE data were used, and 504066 yr when the NOAA network data were used. Our derived lifetime for CFC-113 is higher than the WMO estimates of 85 yr (10488123 using AGAGE, 10387122 using NOAA. Our estimates of the lifetime of CFC-12 and CH3CCl3 agree well with other recent estimates being 10885137 and 10484135 yr (CFC-12, AGAGE and NOAA, respectively and 5.24.85.6 and 5.24.85.7 yr (CH3CCl3, AGAGE and NOAA, respectively.

  19. Re-evaluation of the lifetimes of the major CFCs and CH3CCl3 using atmospheric trends

    Directory of Open Access Journals (Sweden)

    M. Rigby

    2013-03-01

    Full Text Available Since the Montreal Protocol on Substances that Deplete the Ozone Layer and its amendments came into effect, growth rates of the major ozone depleting substances (ODS, particularly CFC-11, -12 and -113 and CH3CCl3, have declined markedly, paving the way for global stratospheric ozone recovery. Emissions have now fallen to relatively low levels, therefore the rate at which this recovery occurs will depend largely on the atmospheric lifetime of these compounds. The first ODS measurements began in the early 1970s along with the first lifetime estimates calculated by considering their atmospheric trends. We now have global mole fraction records spanning multiple decades, prompting this lifetime re-evaluation. Using surface measurements from the Advanced Global Atmospheric Gases Experiment (AGAGE and the National Oceanic and Atmospheric Administration Global Monitoring Division (NOAA GMD from 1978 to 2011, we estimated the lifetime of CFC-11, CFC-12, CFC-113 and CH3CCl3 using a multi-species inverse method. A steady-state lifetime of 45 yr for CFC-11, currently recommended in the most recent World Meteorological Organisation (WMO Scientific Assessments of Ozone Depletion, lies towards the lower uncertainty bound of our estimates, which are 544861 yr (1-sigma uncertainty when AGAGE data were used and 524561 yr when the NOAA network data were used. Our derived lifetime for CFC-113 is significantly higher than the WMO estimates of 85 yr, being 10999121 (AGAGE and 10997124 (NOAA. New estimates of the steady-state lifetimes of CFC-12 and CH3CCl3 are consistent with the current WMO recommendations, being 11195132 and 11295136 yr (CFC-12, AGAGE and NOAA respectively and 5.044.925.20 and 5.044.875.23 yr (CH3CCl3, AGAGE and NOAA respectively.

  20. Re-evaluation of the lifetimes of the major CFCs and CH3CCl3 using atmospheric trends

    Science.gov (United States)

    Rigby, M.; Prinn, R. G.; O'Doherty, S.; Montzka, S. A.; McCulloch, A.; Harth, C. M.; Mühle, J.; Salameh, P. K.; Weiss, R. F.; Young, D.; Simmonds, P. G.; Hall, B. D.; Dutton, G. S.; Nance, D.; Mondeel, D. J.; Elkins, J. W.; Krummel, P. B.; Steele, L. P.; Fraser, P. J.

    2013-03-01

    Since the Montreal Protocol on Substances that Deplete the Ozone Layer and its amendments came into effect, growth rates of the major ozone depleting substances (ODS), particularly CFC-11, -12 and -113 and CH3CCl3, have declined markedly, paving the way for global stratospheric ozone recovery. Emissions have now fallen to relatively low levels, therefore the rate at which this recovery occurs will depend largely on the atmospheric lifetime of these compounds. The first ODS measurements began in the early 1970s along with the first lifetime estimates calculated by considering their atmospheric trends. We now have global mole fraction records spanning multiple decades, prompting this lifetime re-evaluation. Using surface measurements from the Advanced Global Atmospheric Gases Experiment (AGAGE) and the National Oceanic and Atmospheric Administration Global Monitoring Division (NOAA GMD) from 1978 to 2011, we estimated the lifetime of CFC-11, CFC-12, CFC-113 and CH3CCl3 using a multi-species inverse method. A steady-state lifetime of 45 yr for CFC-11, currently recommended in the most recent World Meteorological Organisation (WMO) Scientific Assessments of Ozone Depletion, lies towards the lower uncertainty bound of our estimates, which are 544861 yr (1-sigma uncertainty) when AGAGE data were used and 524561 yr when the NOAA network data were used. Our derived lifetime for CFC-113 is significantly higher than the WMO estimates of 85 yr, being 10999121 (AGAGE) and 10997124 (NOAA). New estimates of the steady-state lifetimes of CFC-12 and CH3CCl3 are consistent with the current WMO recommendations, being 11195132 and 11295136 yr (CFC-12, AGAGE and NOAA respectively) and 5.044.925.20 and 5.044.875.23 yr (CH3CCl3, AGAGE and NOAA respectively).

  1. Pseudogenization of the MCP-2/CCL8 chemokine gene in European rabbit (genus Oryctolagus, but not in species of Cottontail rabbit (Sylvilagus and Hare (Lepus

    Directory of Open Access Journals (Sweden)

    van der Loo Wessel

    2012-08-01

    Full Text Available Abstract Background Recent studies in human have highlighted the importance of the monocyte chemotactic proteins (MCP in leukocyte trafficking and their effects in inflammatory processes, tumor progression, and HIV-1 infection. In European rabbit (Oryctolagus cuniculus one of the prime MCP targets, the chemokine receptor CCR5 underwent a unique structural alteration. Until now, no homologue of MCP-2/CCL8a, MCP-3/CCL7 or MCP-4/CCL13 genes have been reported for this species. This is interesting, because at least the first two genes are expressed in most, if not all, mammals studied, and appear to be implicated in a variety of important chemokine ligand-receptor interactions. By assessing the Rabbit Whole Genome Sequence (WGS data we have searched for orthologs of the mammalian genes of the MCP-Eotaxin cluster. Results We have localized the orthologs of these chemokine genes in the genome of European rabbit and compared them to those of leporid genera which do (i.e. Oryctolagus and Bunolagus or do not share the CCR5 alteration with European rabbit (i.e. Lepus and Sylvilagus. Of the Rabbit orthologs of the CCL8, CCL7, and CCL13 genes only the last two were potentially functional, although showing some structural anomalies at the protein level. The ortholog of MCP-2/CCL8 appeared to be pseudogenized by deleterious nucleotide substitutions affecting exon1 and exon2. By analyzing both genomic and cDNA products, these studies were extended to wild specimens of four genera of the Leporidae family: Oryctolagus, Bunolagus, Lepus, and Sylvilagus. It appeared that the anomalies of the MCP-3/CCL7 and MCP-4/CCL13 proteins are shared among the different species of leporids. In contrast, whereas MCP-2/CCL8 was pseudogenized in every studied specimen of the Oryctolagus - Bunolagus lineage, this gene was intact in species of the Lepus - Sylvilagus lineage, and was, at least in Lepus, correctly transcribed. Conclusion The biological function of a gene was often

  2. Ab initio ro-vibronic spectroscopy of SiCCl (X{sup ~2}Π)

    Energy Technology Data Exchange (ETDEWEB)

    Brites, Vincent [Université d’Evry Val d’Essonne, Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, LAMBE CNRS UMR 8587, Boulevard F. Mitterrand, 91025 Evry Cedex (France); Mitrushchenkov, Alexander O.; Léonard, Céline, E-mail: celine.leonard@u-pem.fr [Université Paris-Est, Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, 5 bd Descartes, 77454 Marne-la-Vallée (France); Peterson, Kirk A. [Department of Chemistry, Washington State University, Pullman, Washington 99164 (United States)

    2014-07-21

    The full dimensional potential energy surfaces of the {sup 2}A{sup ′} and {sup 2}A{sup ′′} electronic components of X{sup ~2}Π SiCCl have been computed using the explicitly correlated coupled cluster method, UCCSD(T)-F12b, combined with a composite approach taking into account basis set incompleteness, core-valence correlation, scalar relativity, and higher order excitations. The spin-orbit and dipole moment surfaces have also been computed ab initio. The ro-vibronic energy levels and absorption spectrum at 5 K have been determined from variational calculations. The influence of each correction on the fundamental frequencies is discussed. An assignment is proposed for bands observed in the LIF experiment of Smith et al. [J. Chem. Phys. 117, 6446 (2002)]. The overall agreement between the experimental and calculated ro-vibronic levels is better than 7 cm{sup −1} which is comparable with the 10–20 cm{sup −1} resolution of the emission spectrum.

  3. Beam Position and Phase Monitors Characterized and Installed in the LANSCE CCL

    Energy Technology Data Exchange (ETDEWEB)

    Gilpatrick, John D [Los Alamos National Laboratory; Kutac, Vincent G. [Los Alamos National Laboratory; Martinez, Derwin [Los Alamos National Laboratory; McCrady, Rodney C. [Los Alamos National Laboratory; O' Hara, James F. [Los Alamos National Laboratory; Olivas, Felix R. [Los Alamos National Laboratory; Shurter, Robert B. [Los Alamos National Laboratory; Watkins, Heath A. [Los Alamos National Laboratory

    2012-04-11

    The Los Alamos Neutron Science Center - Risk Mitigation Project is in the process of replacing older Coupled-Cavity-Linac (CCL) Beam-Position Monitors (BPMs) with newer Beam Position and Phase Monitors (BPPMs) and their associated electronics and cable plants. In many locations, these older BPMs include a separate Delta-T loop for measuring the beam's central phase and energy. Thirty-one BPPMs have been installed and many have monitored the charged particle beam. The installation of these newer BPPMs is the first step to installing complete BPPM measurement systems. Prior to the installation, a characterization of each BPPM took place. The characterization procedure includes a mechanical inspection, a vacuum testing, and associated electrical tests. The BPPM electrical tests for all four electrodes include contact resistance measurements, Time Domain Reflectometer (TDR) measurements, relative 201.25-MHz phase measurements, and finally a set of position-sensitive mapping measurements were performed which included associated fitting routines. This paper will show these data for a typical characterized BPPM.

  4. Human breast cancer-derived soluble factors facilitate CCL19-induced chemotaxis of human dendritic cells.

    Science.gov (United States)

    Hwang, Hyundoo; Shin, Changsik; Park, Juhee; Kang, Enoch; Choi, Bongseo; Han, Jae-A; Do, Yoonkyung; Ryu, Seongho; Cho, Yoon-Kyoung

    2016-01-01

    Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding a crosstalk between breast cancers and immune cells, but little is known about the effect of breast cancer-derived factors on the migratory properties of dendritic cells (DCs) and their consequent capability in inducing T cell immune responses. Utilizing a unique 3D microfluidic device, we here showed that breast cancers (MCF-7, MDA-MB-231, MDA-MB-436 and SK-BR-3)-derived soluble factors increase the migration of DCs toward CCL19. The enhanced migration of DCs was mainly mediated via the highly activated JNK/c-Jun signaling pathway, increasing their directional persistence, while the velocity of DCs was not influenced, particularly when they were co-cultured with triple negative breast cancer cells (TNBCs or MDA-MB-231 and MDA-MB-436). The DCs up-regulated inflammatory cytokines IL-1β and IL-6 and induced T cells more proliferative and resistant against activation-induced cell death (AICD), which secret high levels of inflammatory cytokines IL-1β, IL-6 and IFN-γ. This study demonstrated new possible evasion strategy of TNBCs utilizing their soluble factors that exploit the directionality of DCs toward chemokine responses, leading to the building of inflammatory milieu which may support their own growth. PMID:27451948

  5. Dual blockade of the pro-inflammatory chemokine CCL2 and the homeostatic chemokine CXCL12 is as effective as high dose cyclophosphamide in murine proliferative lupus nephritis.

    Science.gov (United States)

    Devarapu, Satish Kumar; Kumar Vr, Santhosh; Rupanagudi, Khader Valli; Kulkarni, Onkar P; Eulberg, Dirk; Klussmann, Sven; Anders, Hans-Joachim

    2016-08-01

    Induction therapy of proliferative lupus nephritis still requires the use of unselective immunosuppressive drugs with significant toxicities. In search of more specific drugs with equal efficacy but fewer side effects we considered blocking pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) and homeostatic chemokine stromal cell-derived factor-1 (SDF-1/CXCL12), which both contribute to the onset and progression of proliferative lupus nephritis yet through different mechanisms. We hypothesized that dual antagonism could be as potent on lupus nephritis as the unselective immunosuppressant cyclophosphamide (CYC). We estimated serum levels of CCL2 and CXCL12 in patients with SLE (n=99) and compared the results with healthy individuals (n=21). In order to prove our hypothesis we used l-enantiomeric RNA Spiegelmer® chemokine antagonists, i.e. the CCL2-specific mNOX-E36 and the CXCL12-specific NOX-A12 to treat female MRL/lpr mice from week 12 to 20 of age with either anti-CXCL12 or anti-CCL2 alone or both. SLE patients showed elevated serum levels of CCL2 but not of CXCL12. Female MRL/lpr mice treated with dual blockade showed significantly more effective than either monotherapy in preventing proteinuria, immune complex glomerulonephritis, and renal excretory failure and the results are at par with CYC treatment. Dual blockade reduced leukocyte counts and renal IL-6, IL-12p40, CCL-5, CCL-2 and CCR-2 mRNA expression. Dual blockade of CCL2 and CXCL12 can be as potent as CYC to suppress the progression of proliferative lupus nephritis probably because the respective chemokine targets mediate different disease pathomechanisms, i.e. systemic autoimmunity and peripheral tissue inflammation. PMID:27392463

  6. Increase in chemokines CXCL10 and CCL2 in blood from pigs infected with high compared to low virulence African swine fever virus isolates.

    Science.gov (United States)

    Fishbourne, Emma; Hutet, Evelyne; Abrams, Charles; Cariolet, Roland; Le Potier, Marie-Frédérique; Takamatsu, Haru-H; Dixon, Linda K

    2013-10-01

    Modulation of the expression of chemokines and chemokine receptors in whole blood was compared following infection of pigs with high and low virulence isolates of African swine fever virus. Levels of mRNAs for CCL2, CCL3L1, CCL4, CXCL10, CCR1 and CCR5 were significantly increased in at least one time point following infection in two experiments and CCL5, CCR9 and CXCR4 mRNA were significantly increased in one of the experiments. The results showed that greatest fold increases in mRNAs for CXCL10 and CCL2 were observed following infection of pigs. CXCL10 mRNA was increased by up to 15 fold in infected compared to uninfected pigs. CXCL10 protein was also detected in serum from pigs infected with the high virulence Benin 97/1 isolate. Levels of CCL2 mRNA were increased in pigs infected with high virulence Benin 97/1 isolate compared to low virulence OURT88/3 isolate and this correlated with an increase of greater than 30 fold in levels of CCL2 protein detected in serum from pigs infected with this isolate. An increase in overall chemotaxis active compounds in defibrinated plasma samples from Benin 97/1 infected pigs was observed at 3 days post-infection (dpi) and a decrease by 7 dpi as measured by chemotaxis assay using normal pig leucocytes in vitro. Increased levels of CXCL10 may either contribute to the activation of lymphocyte priming toward the Th1 phenotype or induction of T lymphocyte apoptosis. Increased levels of CCL2, a chemoattractant for macrophages, may result in increased recruitment of monocytes from bone marrow thus increasing the pool of cells susceptible to infection.

  7. Association of -1382A>G CCL11 gene variant with ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population

    OpenAIRE

    Sitara Roy; Satrupa Das; Anjana Munshi; Subhash Kaul; Akka Jyothy

    2014-01-01

    Background: CCL11 (Eotaxin-1) is an important inflammatory cytokine belonging to the CC family of chemokines associated with a number of infection or inflammation-related diseases such as atherosclerosis and stroke. We investigated the association of CCL11 gene polymorphism rs4795895-1382A>G with ischemic and hemorrhagic stroke. Materials and Methods: Six hundred and twenty ischemic stroke patients, 620 age- and sex-matched healthy controls, and 220 hemorrhagic stroke patients, 220 age- and s...

  8. Hepatoprotective and cytoprotective properties of Hyptis suaveolens against oxidative stress-induced damage by CCl4 and H2O2

    Institute of Scientific and Technical Information of China (English)

    Hadi Ghaffari; Behrouz Jalali Ghassam; HS Prakash

    2012-01-01

    Objective:To investigate capacity of Hyptis suaveolens (H. suaveolens) methanol extract as an antioxidant to protect against carbon tetrachloride (CCl4)-induced oxidative stress, hepatotoxicity in Albino Wistar rats and cytoprotective effect of hydrogen peroxide (H2O2) induced cell death in HepG2 cell line. Methods: Two different doses of methanol extract of H. suaveolens were evaluated for the hepatoprotective activity against carbon tetrachloride (CCl4) induced hepatotoxicity in rats. Animals in Group I: served as control, group II:H. suaveolens (100 mL/kg b.w), group III:H. suaveolens (50 mL/kg b.w) + CCl4 (1 mg/kg), group IV:H. suaveolens (100 mL/kg b.w) + CCl4 (1 mL/kg) and group V: CCl4 (1 mL/kg). Histopathologic changes of liver were also evaluated. Cytotoxicity was also determined by 3, (4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay. Results:Oral sigle dose treatment of CCl4 produced a marked elevation in the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH). Histopathological analysis of the liver of CCl4-induced rats revealed marked liver cell necrosis with inflammatory collections that were conformed to increase in the levels of SOD, GSH, GST, GR and LPO. Treatment with H2O2 significantly induced death of HepG2 cell. Pretreatment with H. suaveolens methanol extract inhibited or attenuated H2O2 induced cytotoxicity. Conclusions: This study shows that H. suaveolens methanol extract can be proposed to protect the liver against CCl4-induced oxidative damage in rats and protect the cells against H2O2-induced oxidative damage in HepG2 cells. The hepatoprotective and cytoprotective effects might be correlated with its antioxidant and free radical scavenger effects.

  9. A Novel Role for CCL3 (MIP-1α) in Myeloma-induced Bone Disease via Osteocalcin Downregulation and Inhibition of Osteoblast Function

    OpenAIRE

    Vallet, Sonia; Pozzi, Samantha; Patel, Kishan; Vaghela, Nileshwari; Fulciniti, Mariateresa; Veiby, Petter; Hideshima, Teru; Santo, Loredana; Cirstea, Diana; Scadden, David T.; Anderson, Kenneth C.; Raje, Noopur

    2011-01-01

    Upregulation of cytokines and chemokines is a frequent finding in multiple myeloma (MM). CCL3 (also known as MIP-1α) is a pro-inflammatory chemokine whose levels in the MM microenvironment correlate with osteolytic lesions and tumor burden. CCL3 and its receptors, CCR1 and CCR5, contribute to the development of bone disease in MM by supporting tumor growth and regulating osteoclast (OC) differentiation. Here, we identify inhibition of osteoblast (OB) function as an additional pathogenic mecha...

  10. Red Sea Suberea mollis Sponge Extract Protects against CCl4-Induced Acute Liver Injury in Rats via an Antioxidant Mechanism

    Directory of Open Access Journals (Sweden)

    Aymn T. Abbas

    2014-01-01

    Full Text Available Recent studies have demonstrated that marine sponges and their active constituents exhibited several potential medical applications. This study aimed to evaluate the possible hepatoprotective role as well as the antioxidant effect of the Red Sea Suberea mollis sponge extract (SMSE on carbon tetrachloride- (CCl4- induced acute liver injury in rats. In vitro antioxidant activity of SMSE was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH assay. Rats were orally administered three different concentrations (100, 200, and 400 mg/kg of SMSE and silymarin (100 mg/kg along with CCl4 (1 mL/kg, i.p., every 72 hr for 14 days. Plasma aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, and total bilirubin were measured. Hepatic malondialdehyde (MDA, reduced glutathione (GSH, nitric oxide (NO, superoxide dismutase (SOD, glutathione peroxidase (GPx, and catalase (CAT were also measured. Liver specimens were histopathologically examined. SMSE showed strong scavenging activity against free radicals in DPPH assay. SMSE significantly reduced liver enzyme activities. Moreover, SMSE significantly reduced hepatic MDA formation. In addition, SMSE restored GSH, NO, SOD, GPx, and CAT. The histopathological results confirmed these findings. The results of this study suggested a potent protective effect of the SMSE against CCl4-induced hepatic injury. This may be due to its antioxidant and radical scavenging activity.

  11. In-Vivo Antioxidant activity of ethanolic extract of Mentha pulegium leaf against CCl4 induced toxicity in rats

    Institute of Scientific and Technical Information of China (English)

    Sachin Jain; Dinesh Kumar Jain; Neelam Balekar

    2012-01-01

    Objective: To evaluate the in-vivo antioxidant potential of ethanolic extract of Mentha Pulegium against CCl4 induced toxicity in rats. Methods: Animals were treated with plant extract for 7 days and then toxicity was induced with a single CCl4 intraperitoneal injection. Pre-treatment with 600 mg/kg (p.o.) of ethanolic extract of Mentha Pulegium improved the glutathione, SOD, catalase, and peroxidase levels significantly as compared to control group. Results: The present studies revealed that Mentha Pulegium has significant in-vivo antioxidant activity and can be used to protect tissue from oxidative stress. The result showed that the activities of glutathione, SOD, catalase and peroxidase in group treated with CCl4 declined significantly than that of normal group. Conclusion: Ethanolic extract of Mentha Pulegium in the dose of 600 mg/kg, p.o., has improved the glutathione, SOD, catalase, and peroxidase levels significantly, which were comparable with Liv 52. Based on this study we conclude that Ethanolic extract of MenthaPulegium possesses in vivo antioxidant activity and can be employed in protecting tissue from oxidative stress.

  12. Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl4-induced chronic liver damage in rats

    Institute of Scientific and Technical Information of China (English)

    Yun-Kyoung Yim; Hyun Lee; Kwon-Eui Hong; Young-Il Kim; Byung-Ryul Lee; Tae-Han Kim; Ji-Young Yi

    2006-01-01

    AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats.METHODS: Rats were injected intraperitoneally with CCl4 (1 mL/kg) and treated with manual acupuncture using reinforcing manipulation techniques at left GB34(Yanglingquan) 3 times a week for 10 wk. A nonacupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index,biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted.RESULTS: Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes.CONCLUSION: Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCl4-intoxicated rats.

  13. The ethanolic extract of Juglans sinensis leaves and twigs attenuates CCl4-induced hepatic oxidative stress in rats

    Directory of Open Access Journals (Sweden)

    Heejung Yang

    2015-01-01

    Full Text Available Background: The nuts of Juglans sinensis Dode, walnut tree, are rich in unsaturated fatty acids and bioactive compounds with antioxidant activity on liver damages. However, hepatoprotective activity of the leaves and twigs of J. sinensis have not intensively studied yet. Objective: Hepatoprotective activity of the refined ethanolic extract of J. sinensis (JSE3 was evaluated using carbon tetrachloride (CCl4 intoxicated rats. Materials and Methods: Hepatotoxicity was induced in Sprague Dawley rats by intraperitoneal injection of CCl4 for 6 weeks in the presence or absence of JSE3 (100 and 200 mg/kg body weight. The hepatoprotective activity of JSE3 was assessed by biochemical parameters including plasma aspartate aminotransferase (AST, alanine aminotransferase (ALT, and antioxidant enzymes, such as superoxide dismutase (SOD, glutathione reductase, glutathione peroxide, reduced glutathione and oxidized glutathione, along with histopathological studies on hepatic tissue. Results: JSE3 significantly decreased the elevated levels of AST and ALT and restored the reduced levels of antioxidant enzymes. JSE3 also decreased the amounts of collagen content accumulated by CCl4 intoxication. Conclusion: These results suggested that the refined extract of J. sinensis may have a potential to be developed as a therapeutic agent to treat hepatic diseases, such as fatty liver and hepatic fibrosis.

  14. Maraviroc decreases CCL8-mediated migration of CCR5(+) regulatory T cells and reduces metastatic tumor growth in the lungs.

    Science.gov (United States)

    Halvorsen, E C; Hamilton, M J; Young, A; Wadsworth, B J; LePard, N E; Lee, H N; Firmino, N; Collier, J L; Bennewith, K L

    2016-06-01

    Regulatory T cells (Tregs) play a crucial physiological role in the regulation of immune homeostasis, although recent data suggest Tregs can contribute to primary tumor growth by suppressing antitumor immune responses. Tregs may also influence the development of tumor metastases, although there is a paucity of information regarding the phenotype and function of Tregs in metastatic target organs. Herein, we demonstrate that orthotopically implanted metastatic mammary tumors induce significant Treg accumulation in the lungs, which is a site of mammary tumor metastasis. Tregs in the primary tumor and metastatic lungs express high levels of C-C chemokine receptor type 5 (CCR5) relative to Tregs in the mammary fat pad and lungs of tumor-free mice, and Tregs in the metastatic lungs are enriched for CCR5 expression in comparison to other immune cell populations. We also identify that C-C chemokine ligand 8 (CCL8), an endogenous ligand of CCR5, is produced by F4/80(+) macrophages in the lungs of mice with metastatic primary tumors. Migration of Tregs toward CCL8 ex vivo is reduced in the presence of the CCR5 inhibitor Maraviroc. Importantly, treatment of mice with Maraviroc (MVC) reduces the level of CCR5(+) Tregs and metastatic tumor burden in the lungs. This work provides evidence of a CCL8/CCR5 signaling axis driving Treg recruitment to the lungs of mice bearing metastatic primary tumors, representing a potential therapeutic target to decrease Treg accumulation and metastatic tumor growth.

  15. Hepatoprotective potential of ethanolic and aqueous extract of flowers of Sesbania grandiflora (Linn) induced by CCl4

    Institute of Scientific and Technical Information of China (English)

    Ishwer Kale; Mohd Asif Khan; Yusufuddin Irfan; Veerana Goud A

    2012-01-01

    Objective: To investigate the hepatoprotective activity of ethanolic and aqueous extract of Sesbania grandiflora(Linn) flower in CCl4 induced hepatotoxicity models in rats. Methods:The ethanolic and aqueous extract of Sesbania grandiflora (Linn) flower are screened for its hepatoprotective activity in CCl4 (0.5 ml/kg, i.p) induced liver damage in Swiss albino rats at a dose of 200 mg/kg bw. Results: The ethanolic and aqueous extract of Sesbania grandiflora (Linn) flower significantly (P<0.001) decreases the biochemical parameters (SGOT, SGPT, ALP, TP, and TB). Silymarin (25 mg/kg), a known hepatoprotective drug used for comparison exhibited significant activity (P<0.001). The extract did not shown any mortality up to a dose of 2000 g/kg bw. These findings suggest that the ethanolic and aqueous extract of Sesbania grandiflora (Linn) flower (500mg/kg) was effective in bringing about functional improvement of hepatocytes. The healing effect of this extract was also confirmed by histological observations. Conclusions: The ethanolic extract at doses of 250 and 500 mg/kg, p.o. and aqueous extract at a dose of 500 mg/kg, p.o. of Sesbania grandiflora (Linn) flower have significant effect on the liver of CCl4 induced hepatotoxicity animal models.

  16. Low Intraprostatic DHT Promotes the Infiltration of CD8+ T Cells in BPH Tissues via Modulation of CCL5 Secretion

    Directory of Open Access Journals (Sweden)

    Yu Fan

    2014-01-01

    Full Text Available Clinical studies suggested thatandrogen might be associated with infiltrating T cells in prostate of benign prostatic hyperplasia (BPH patients, but detail of T-cell subset and mechanism still remained unclear. The present study tested the hypothesis that intraprostatic 5α-dihydrotestosterone (DHT exerts effects on T cells recruitment by BPH epithelial cells. Prostate tissues from 64 cases of BPH patients after transurethral resection of prostate (TURP were divided into 2 groups: (1 no medication history; (2 administration of 5α-reductase type II inhibitor-finasteride 5 mg daily for at least 6 months before surgery. Group 2 presented significantly higher CD8+ T cells infiltration than group 1, but no changes in CD4+ T cells (immunohistochemistry and flow cytometry. In vitro study more CD8+ T cell migrated to the prostate tissue lysates from group 2 and BPH-1 cells in low DHT condition. Transcription of chemokine (C-C motif Ligand 5 (CCL5 mRNA in BPH-1 cells and chemokine (C-C motif receptor 5 (CCR5 mRNA in CD8+ T cells were upregulated in low DHT condition (q-PCR. CCL5 expression was also identified to be higher in group 2 prostate tissues by IHC. This study suggested that intraprostatic DHT may participate in regulating inflammatory response which was induced by human prostatic epithelial cell, via modulating CCL5 secretion.

  17. Immunotherapeutic effects of cytokine-induced killer cells combined with CCL21/IL15 armed oncolytic adenovirus in TERT-positive tumor cells.

    Science.gov (United States)

    Ye, Jun-Feng; Lin, Yuan-Qiang; Yu, Xiu-Hua; Liu, Ming-Yuan; Li, Yang

    2016-09-01

    The effective antitumor immune responses are dependent on coordinate interaction of various effector cells. Thus, the combination of adoptive immunotherapy and target gene therapy is capable of efficiently generating a productive antitumor immune response. We investigated whether combination of cytokine-induced killer (CIK) cells adoptive immunotherapy and CCL21/IL15 armed oncolytic adenovirus could induce the enhanced antitumor activity. The CCL21/IL15 co-expression oncolytic adenoviruses were constructed by using the AdEasy system, which uses homologous recombination with shuttle plasmids and full length Ad backbones. This conditionally replicating adenoviruses CRAd-CCL21-IL15 could induce apoptosis in TERTp-positive tumor cells for viral propagation, but do not replicate efficiently in normal cells, because the E1A promoter was replaced by telomerase reverse transcriptase promoter (TERTp). Our results showed that the combination of CIK cells and CRAd-CCL21-IL15 could induce higher antitumor activity than either CIK cells or CRAd-CCL21-IL15 alone. This combined treatment could induce the tumor specific cytotoxicity of CTLs (cytotoxic T lymphocytes) in vitro. Moreover, the treatment of established tumors with the combined therapy of CIK cells and CRAd-CCL21-IL15 resulted in tumor regression. This study suggests that the combined treatment by adoptive immunotherapy and gene therapy is a promising strategy for the therapy of tumor. PMID:27380620

  18. Inter-laboratory comparison of methods to measure androstenone in pork fat.

    Science.gov (United States)

    Ampuero Kragten, S; Verkuylen, B; Dahlmans, H; Hortos, M; Garcia-Regueiro, J A; Dahl, E; Andresen, O; Feitsma, H; Mathur, P K; Harlizius, B

    2011-08-01

    Today, different analytical methods are used by different laboratories to quantify androstenone in fat tissue. This study shows the comparison of methods used routinely in different laboratories for androstenone quantification: Time-resolved fluoroimmunoassay in Norwegian School of Veterinary Science (NSVS; Norway), gas chromatography coupled to mass spectrometry in Co-operative Central Laboratory (CCL; The Netherlands) and in Institut de Recerca i Tecnologia Agroalimentàries (IRTA; Spain), and high-pressure liquid chromatography in Agroscope Liebefeld-Posieux Research Station (ALP; Switzerland). In a first trial, a set of adipose tissue (AT) samples from 53 entire males was sent to CCL, IRTA and NSVS for determination of androstenone concentration. The average androstenone concentration (s.d.) was 2.47 (2.10) μg/g at NSVS, 1.31 (0.98) μg/g at CCL and 0.62 (0.52) μg/g at IRTA. Despite the large differences in absolute values, inter-laboratory correlations were high, ranging from 0.82 to 0.92. A closer look showed differences in the preparation step. Indeed, different matrices were used for the analysis: pure fat at NSVS, melted fat at CCL and AT at IRTA. A second trial was organised in order to circumvent the differences in sample preparation. Back fat samples from 10 entire males were lyophilised at the ALP labortary in Switzerland and were sent to the other laboratories for androstenone concentration measurement. The average concentration (s.d.) of androstenone in the freeze-dried AT samples was 0.87 (0.52), 1.03 (0.55), 0.84 (0.46) and 0.99 (0.67) μg/g at NSVS, CCL, IRTA and ALP, respectively, and the pairwise correlations between laboratories ranged from 0.92 to 0.97. Thus, this study shows the influence of the different sample preparation protocols, leading to major differences in the results, although still allowing high inter-laboratory correlations. The results further highlight the need for method standardisation and inter-laboratory ring tests for

  19. Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver.

    Science.gov (United States)

    Mikula, Michal; Majewska, Aneta; Ledwon, Joanna Karolina; Dzwonek, Artur; Ostrowski, Jerzy

    2014-12-01

    Obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; also known as Ccl2). However, the chromatin make-up at these genes in the liver in obese individuals has not been explored. In this study, to identify obesity-mediated epigenetic changes at Tnfa and Ccl2, we used a murine model of obesity induced by a high-fat diet (HFD) and hyperphagic (ob/ob) mice. Chromatin immunoprecipitation (ChIP) assay was used to determine the abundance of permissive histone marks, namely histone H3 lysine 9 and 18 acetylation (H3K9/K18Ac), H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 36 trimethylation (H3K36me3), in conjunction with polymerase 2 RNA (Pol2) and nuclear factor (Nf)-κB recruitment in the liver. Additionally, to correlate the liver tissue-derived ChIP measurements with a robust in vitro transcriptional response at the Tnfa and Ccl2 genes, we used lipopolysaccharide (LPS) treatment to induce an inflammatory response in Hepa1-6 cells, a cell line derived from murine hepatocytes. ChIP revealed increased H3K9/K18Ac at Tnfa and Ccl2 in the obese mice, although the differences were only statistically significant for Tnfa (pgenes in the obese mice. By contrast, the acute treatment of Hepa1-6 cells with LPS significantly increased the H3K9/K18Ac marks, as well as Pol2 and Nf-κB recruitment at both genes, while the levels of H3K4me3 and H3K36me3 marks remained unaltered. These results demonstrate that increased Tnfa and Ccl2 expression in fatty liver at the chromatin level corresponds to changes in the level of histone H3 acetylation.

  20. Role of CCL3L1-CCR5 genotypes in the epidemic spread of HIV-1 and evaluation of vaccine efficacy.

    Directory of Open Access Journals (Sweden)

    Hemant Kulkarni

    Full Text Available BACKGROUND: Polymorphisms in CCR5, the major coreceptor for HIV, and CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine, are determinants of HIV-AIDS susceptibility. Here, we mathematically modeled the potential impact of these genetic factors on the epidemic spread of HIV, as well as on its prevention. METHODS AND RESULTS: Ro, the basic reproductive number, is a fundamental concept in explaining the emergence and persistence of epidemics. By modeling sexual transmission among HIV+/HIV- partner pairs, we find that Ro estimates, and concordantly, the temporal and spatial patterns of HIV outgrowth are highly dependent on the infecting partners' CCL3L1-CCR5 genotype. Ro was least and highest when the infected partner possessed protective and detrimental CCL3L1-CCR5 genotypes, respectively. The modeling data indicate that in populations such as Pygmies with a high CCL3L1 gene dose and protective CCR5 genotypes, the spread of HIV might be minimal. Additionally, Pc, the critical vaccination proportion, an estimate of the fraction of the population that must be vaccinated successfully to eradicate an epidemic was 1, to prevent epidemic spread, population groups defined by specific CCL3L1-CCR5 genotypes might require repeated vaccination, or as our models suggest, a vaccine with an efficacy of >70%. Further, failure to account for CCL3L1-CCR5-based genetic risk might confound estimates of vaccine efficacy. For example, in a modeled trial of 500 subjects, misallocation of CCL3L1-CCR5 genotype of only 25 (5% subjects between placebo and vaccine arms results in a relative error of approximately 12% from the true vaccine efficacy. CONCLUSIONS: CCL3L1-CCR5 genotypes may impact on the dynamics of the HIV epidemic and, consequently, the observed heterogeneous global distribution of HIV infection. As Ro is lowest when the infecting partner has beneficial CCL3L1-CCR5 genotypes, we infer that therapeutic vaccines directed towards reducing the infectivity

  1. Small interfering RNA-mediated suppression of Ccl2 in Müller cells attenuates microglial recruitment and photoreceptor death following retinal degeneration

    Directory of Open Access Journals (Sweden)

    Rutar Matt

    2012-09-01

    Full Text Available Abstract Background The recruitment and activation of inflammatory cells is thought to exacerbate photoreceptor death in retinal degenerative conditions such as age-related macular degeneration (AMD. We investigated the role of Müller cell-derived chemokine (C-C motif ligand (Ccl2 expression on monocyte/microglia infiltration and photoreceptor death in light-mediated retinal degeneration, using targeted small interfering (siRNA. Methods Adult Sprague–Dawley rats were injected intravitreally with 1 μg of either Ccl2 siRNA or scrambled siRNA, and were then exposed to 1000 lux of light for a period of 24 hours. The mice were given an overdose of barbiturate, and the retinas harvested and evaluated for the effects of bright-light exposure. Ccl2 expression was assessed by quantitative PCR, immunohistochemistry, and in situ hybridization. Monocytes/microglia were counted on retinal cryostat sections immunolabeled with the markers ED1 and ionized calcium binding adaptor (IBA1, and photoreceptor apoptosis was assessed using terminal dUTP nick end labeling. Results Intravitreal injection of Ccl2 siRNA significantly reduced the expression of Ccl2 following light damage to 29% compared with controls. In retinas injected with Ccl2 siRNA, in situ hybridization and immunohistochemistry on retinal cryostat sections showed a substantial decrease in Ccl2 within Müller cells. Cell counts showed significantly fewer ED1-positive and IBA1-positive cells in the retinal vasculature and outer nuclear layer of Ccl2 siRNA-injected retinas, compared with controls. Moreover, there was significantly less photoreceptor apoptosis in Ccl2 siRNA-injected retinas compared with controls. Conclusions Our data indicate that Ccl2 expression by Müller cells promotes the infiltration of monocytes/microglia, thereby contributing to the neuroinflammatory response and photoreceptor death following retinal injury. Modulation of exaggerated chemokine responses using siRNA may have

  2. Transport properties of stage-1 CucCo1-cCl2 graphite intercalation compounds

    International Nuclear Information System (INIS)

    Stage-1 CucCo1-cCl2 graphite intercalation compounds approximate quasi-two-dimensional (2D) random spin systems with competing ferromagnetic and antiferromagnetic intraplanar exchange interactions. The temperature dependence of the in-plane electrical resistivity of these compounds has been measured near critical temperatures. The magnetic resistivity ζmag consists of the long-range spin-order part ζLS and the spin-fluctuation part ζSF. For 0≤c≤0.2 the long-range spin-order part ζLS is dominant: the temperature dependence of ζLS is described by a smeared power law with an exponent 2β, where β is the critical exponent of staggered magnetization. For 0.3≤c≤0.4 the spin-fluctuation part ζSF becomes larger than ζLS. For 0.5≤c≤0.95 no appreciable magnetic resistivity is observed. For c=1 the derivative -dζmag/dT shows a small peak at around 67 K due to the growth of short-range spin order which is characteristic of the 2D Heisenberg antiferromagnet. The critical behaviour of the in-plane resistivity can be explained in terms of a model based on π-d exchange interactions between π-electrons in the graphite layers and magnetic spins in the intercalate layers. The π-electrons are scattered by spins of a virtual antiferromagnetic in-plane spin configuration arising from the superposition of two ferromagnetic in-plane structures with spin directions antiparallel to each other. The π- d exchange interactions of these compounds are also discussed. (author)

  3. Analytical Laboratories

    Data.gov (United States)

    Federal Laboratory Consortium — NETL’s analytical laboratories in Pittsburgh, PA, and Albany, OR, give researchers access to the equipment they need to thoroughly study the properties of materials...

  4. Computational Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory contains a number of commercial off-the-shelf and in-house software packages allowing for both statistical analysis as well as mathematical modeling...

  5. National laboratories

    International Nuclear Information System (INIS)

    The foundation of a 'National Laboratory' which would support a Research center in synchrotron radiation applications is proposed. The essential features of such a laboratory differing of others centers in Brazil are presented. (L.C.)

  6. Laboratory Tests

    Science.gov (United States)

    Laboratory tests check a sample of your blood, urine, or body tissues. A technician or your doctor ... compare your results to results from previous tests. Laboratory tests are often part of a routine checkup ...

  7. CCL3L1 gene copy number in individuals with and without HIV-associated neurocognitive disorder

    Directory of Open Access Journals (Sweden)

    Brown A

    2012-01-01

    Full Text Available Amanda Brown1, Ned Sacktor1, Karen Marder2, Bruce Cohen3, Giovanni Schifitto4, Richard L Skolasky1, Jason Creighton1, Liping Guo1, Justin C McArthur11Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 2Department of Neurology, Psychiatry, Sergievsky Center and Taub Institute on Alzheimers Disease and the Aging Brain, New York Presbyterian Hospital, Columbia University College of Physicians and Surgeons, New York, NY, 3Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, 4Department of Neurology, University of Rochester, School of Medicine and Dentistry, Rochester, NY, USABackground: CCL3L1 copy number variation has been implicated as a marker for susceptibility and immunity to human immunodeficiency virus (HIV-1 infection and its pathogenic sequelae. Some of these findings have been confirmed in several, but not all, subsequent independent cohort studies. A three-fold risk for the development of HIV-associated dementia was reported in individuals possessing a CCL3L1 copy number below the ethnic group median combined with a detrimental CCR5 genotype. With the availability of antiretroviral therapy since 1996, there has been a significant decline in HIV-associated dementia, and milder forms of HIV-associated neurocognitive impairment (HAND are now most prevalent. Moreover, patients are living longer with HIV-1 infection and it is recognized that aging may be a contributory factor to the development of cognitive disorder. Thus, the need for biomarkers that can be used in clinical practice to identify and provide optimal treatment for those at increased risk for HAND is great. HAND affects 20%–30% of HIV-infected individuals, and several genetic loci which have been shown to confer susceptibility to HIV infection may also modulate the development of neurocognitive disorder. The aim of this study was to determine whether CCL3L1 chemokine gene copy number in self-defined ethnic

  8. CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion

    Directory of Open Access Journals (Sweden)

    Lillard James W

    2011-05-01

    Full Text Available Abstract Background Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites. Metastasis and chemoresistance are responsible for most cancer-related deaths; hence, therapies designed to minimize both are greatly needed. We have recently shown that CCR9-CCL25 interactions promote BrCa cell migration and invasion, while others have shown that this axis play important role in T cell survival. In this study we have shown potential role of CCR9-CCL25 axis in breast cancer cell survival and therapeutic efficacy of cisplatin. Methods Bromodeoxyuridine (BrdU incorporation, Vybrant apoptosis and TUNEL assays were performed to ascertain the role of CCR9-CCL25 axis in cisplatin-induced apoptosis of BrCa cells. Fast Activated Cell-based ELISA (FACE assay was used to quantify In situ activation of PI3Kp85, AktSer473, GSK-3βSer9 and FKHRThr24 in breast cancer cells with or without cisplatin treatment in presence or absence of CCL25. Results CCR9-CCL25 axis provides survival advantage to BrCa cells and inhibits cisplatin-induced apoptosis in a PI3K-dependent and focal adhesion kinase (FAK-independent fashion. Furthermore, CCR9-CCL25 axis activates cell-survival signals through Akt and subsequent glycogen synthase kinase-3 beta (GSK-3β and forkhead in human rhabdomyosarcoma (FKHR inactivation. These results show that CCR9-CCL25 axis play important role in BrCa cell survival and low chemotherapeutic efficacy of cisplatin primarily through PI3K/Akt dependent fashion.

  9. Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP and CCL11/eotaxin-1 in human asthmatic airways.

    Directory of Open Access Journals (Sweden)

    Gustavo Nino

    Full Text Available BACKGROUND: Thymic stromal lymphoproetin (TSLP is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. METHODS: Primary human bronchial epithelial cells (HBEC from control (n = 3 and asthmatic (n = 3 donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI conditions and treated apically with dsRNA (viral surrogate or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC from normal (n = 3 and asthmatic (n = 3 donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20 vs. non-asthmatic uninfected controls (n = 20. Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. RESULTS: Our data demonstrate that: 1 Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2 TSLP exposure induces unidirectional (apical secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3 Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. CONCLUSIONS: There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

  10. Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders

    Directory of Open Access Journals (Sweden)

    Carpenter Danielle

    2011-08-01

    Full Text Available Abstract Background Copy number variation (CNV contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. Results We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. Conclusions Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.

  11. mTORC2-PKBα/Akt1 Serine 473 phosphorylation axis is essential for regulation of FOXP3 Stability by chemokine CCL3 in psoriasis.

    Science.gov (United States)

    Chen, Ling; Wu, Jinjin; Pier, Eric; Zhao, Yun; Shen, Zhu

    2013-02-01

    The connection between infections and acute guttate psoriasis (AGP) outbreaks/chronic plaque psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of psoriasis.

  12. Protective effect of rhizoma polygoni cuspidati decoction on liver fibrosis induced by CCL4%中药虎杖水煎液对CCL4诱导肝纤维化的保护作用

    Institute of Scientific and Technical Information of China (English)

    杨先振; 赵有亮; 秦红兵

    2011-01-01

    目的 观察虎杖水煎液对四氯化碳(CCL4)诱导肝纤维化的作用.方法 40只大鼠随机均分为正常对照(A)组、肝纤维化模型(B)组、虎杖水煎液低剂量3 g/kg(C)组和高剂量6 g/kg(D)组.10周后,检测血清ALT、AST以及肝纤维化血清标志物透明质酸(HA)与Ⅵ型胶原(C-Ⅳ)水平,测定肝组织匀浆中超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量,并取肝组织做病理形态学检查.结果 与B组相比,C、D组血清ALT、AST、HA和C-Ⅳ水平降低,肝组织中MDA含量减少,而SOD活性增加(P<0.05或P<0.01),肝纤维化的组织学改变亦减轻.结论 虎杖水煎液对CCL4诱导的肝纤维化具有一定保护作用.%Objective To investigate the effect of rhizoma polygoni cuspidati(RPC) decoction on the liver fibrosis induced by carbon tetrachloride ( CCL4 ). Methods Forty rats were equally randomized into four groups of A(normal controls),B(liver fibrosis model),C(liver fibrosis treated with RPC decoction 3 g/kg) and D( liver fibrosis treated with RPC decoction 6 g/kg). After 10 weeks of administration, serum alanine aminotransferase( ALT), aspartate aminotransf erase (AST) and liver fibrosis markers such as hyaluronic acid(HA) and collagen type W(C-IV) were detected, the activity of superoxide dismutase(SOD) and content of malondialdehyde(MDA) in the hepatic homogenates were measured and the changes of pathomorphology were observed by light microscopy. Results Compared with group B.the levels of ALT, AST, HA,C-IV and the content of MDA were decreased, while the activity of SOD was increased (P<0. 05 or P<0. 01) and the histological changes of liver fibrosis were also improved in groups of C and D. Conclusion RPC decoction has a protective effect on the liver fibrosis induced by CCL4.

  13. In vivo Cigarette Smoke Exposure Decreases CCL20, SLPI, and BD-1 Secretion by Human Primary Nasal Epithelial Cells

    Science.gov (United States)

    Jukosky, James; Gosselin, Benoit J.; Foley, Leah; Dechen, Tenzin; Fiering, Steven; Crane-Godreau, Mardi A.

    2016-01-01

    Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of primary human nasal epithelial cells (PHNECs). Compared to non-CS-exposed individuals, PHNEC from in vivo CS-exposed individuals secreted less chemokine ligand (C-C motif) 20 (CCL20), Beta-defensin 1 (BD-1), and SLPI apically, less BD-1 and SLPI basolaterally, and more CCL20 basolaterally. Cigarette smoke extract (CSE) exposure in vitro decreased the apical secretion of CCL20 and beta-defensin 1 by PHNEC from non-CS-exposed individuals. Exposing PHNEC from non-CS exposed to CSE also significantly decreased the levels of many mRNA transcripts that are involved in immune signaling. Our results show that in vivo or in vitro exposure to CS alters the secretion of key antimicrobial peptides from PHNEC, but that in vivo CS exposure is a much more important modifier of antimicrobial peptide secretion. Based on the gene expression data, it appears that CSE disrupts multiple immune signaling pathways in PHNEC. Our results provide mechanistic insight into how CS exposure alters the innate immune response and increases an individual’s susceptibility to pathogen infection. PMID:26793127

  14. Reprogramming of Normal Fibroblasts into Cancer-Associated Fibroblasts by miRNAs-Mediated CCL2/VEGFA Signaling

    Science.gov (United States)

    Shen, Hua; Yu, Xiaobo; Yang, Fengming; Zhang, Zhihua; Shen, Jianxin; Sun, Jin; Choksi, Swati; Jitkaew, Siriporn; Shu, Yongqian

    2016-01-01

    Cancer-associated fibroblasts (CAFs), the most common constituent of the tumor stoma, are known to promote tumor initiation, progression and metastasis. However, the mechanism of how cancer cells transform normal fibroblasts (NFs) into CAFs is largely unknown. In this study, we determined the contribution of miRNAs in the transformation of NFs into CAFs. We found that miR-1 and miR-206 were down-regulated, whereas miR-31 was up-regulated in lung CAFs when compared with matched NFs. Importantly, modifying the expression of these three deregulated miRNAs induced a functional conversion of NFs into CAFs and vice versa. When the miRNA-reprogrammed NFs and CAFs were co-cultured with lung cancer cells (LCCs), a similar pattern of cytokine expression profiling were observed between two groups. Using a combination of cytokine expression profiling and miRNAs algorithms, we identified VEGFA/CCL2 and FOXO3a as direct targets of miR-1, miR-206 and miR-31, respectively. Importantly, systemic delivery of anti-VEGFA/CCL2 or pre-miR-1, pre-miR-206 and anti-miR-31 significantly inhibited tumor angiogenesis, TAMs accumulation, tumor growth and lung metastasis. Our results show that miRNAs-mediated FOXO3a/VEGF/CCL2 signaling plays a prominent role in LCCs-mediated NFs into CAFs, which may have clinical implications for providing novel biomarker(s) and potential therapeutic target(s) of lung cancer in the future. PMID:27541266

  15. CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells

    OpenAIRE

    Rom, Slava; Rom, Inna; Passiatore, Giovanni; Pacifici, Marco; Radhakrishnan, Sujatha; Del Valle, Luis; Piña-Oviedo, Sergio; Khalili, Kamel; Eletto, Davide; Peruzzi, Francesca

    2010-01-01

    MicroRNA-mediated regulation of gene expression appears to be involved in a variety of cellular processes, including development, differentiation, proliferation, and apoptosis. Mir-146a is thought to be involved in the regulation of the innate immune response, and its expression is increased in tissues associated with chronic inflammation. Among the predicted gene targets for mir-146a, the chemokine CCL8/MCP-2 is a ligand for the CCR5 chemokine receptor and a potent inhibitor of CD4/CCR5-medi...

  16. Rapamycin ameliorates CCl4-induced liver fibrosis in mice through reciprocal regulation of the Th17/Treg cell balance.

    Science.gov (United States)

    Gu, Lei; Deng, Wen-Sheng; Sun, Xiao-Fei; Zhou, Hong; Xu, Qing

    2016-08-01

    Previous investigations have suggested that the activation of Th17 cells and/or deficiency of regulatory T cells (Tregs) are involved in the pathogenesis of liver fibrosis. The aim of the present study was to investigate the effect of rapamycin on immune responses in a carbon tetrachloride (CCl4)-induced murine liver fibrosis model. Liver fibrosis was induced by intraperitoneal administration with CCl4. Following injection of CCl4, the mice were treated intraperitoneally with rapamycin (1.25 mg/kg/day) for 8 weeks. Hematoxylin and eosin staining and Masson's trichrome staining were used for histological examination. The protein levels of forkhead/winged helix transcription factor P3, retinoic-acid-related orphan receptor (ROR)‑γt in liver tissue were determined by western blotting, the frequency of Th17 and Treg cells in the liver was evaluated by flow cytometry, and a suppression assay was measured by incorporating [3H]‑thymidine. In addition, to explore the effect of Tregs expanded with rapamycin on hepatic stellate cells (HSC), HSCs were co‑cultured with Tregs from rapamycin or phosphate‑buffered saline‑treated mice. It was found that rapamycin treatment led to a significant reduction in the number of Th17 cells and in the expression levels of ROR‑γt in the liver tissues. Simultaneously, the results of the present study showed a significant increase in the frequency of Tregs and a marked enhancement in the expression of forkhead/winged helix transcription factor P3 in the rapamycin‑treated mice. Furthermore, the Tregs in rapamycin‑treated mice had significantly higher suppressive effects, compared with the cells from mice treated with phospphate‑buffered saline. Consequently, rapamycin treatment prevented the development of CCl4-induced hepatic fibrosis, which was shown by its histological appearances. These results suggested that the immunosuppressive effect of rapamycin on liver fibrosis was associated with the suppression of hepatic

  17. Recombinant VP1, an Akt inhibitor, suppresses progression of hepatocellular carcinoma by inducing apoptosis and modulation of CCL2 production.

    Directory of Open Access Journals (Sweden)

    Tai-An Chen

    Full Text Available BACKGROUND: The application of viral elements in tumor therapy is one facet of cancer research. Recombinant capsid protein VP1 (rVP1 of foot-and-mouth disease virus has previously been demonstrated to induce apoptosis in cancer cell lines. Here, we aim to further investigate its apoptotic mechanism and possible anti-metastatic effect in murine models of hepatocellular carcinoma (HCC, one of the most common human cancers worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with rVP1 inhibited cell proliferation in two murine HCC cell lines, BNL and Hepa1-6, with IC₅₀ values in the range of 0.1-0.2 µM. rVP1 also induced apoptosis in these cells, which was mediated by Akt deactivation and dissociation of Ku70-Bax, and resulted in conformational changes and mitochondrial translocation of Bax, leading to the activation of caspases-9, -3 and -7. Treatment with 0.025 µM rVP1, which did not affect the viability of normal hepatocytes, suppressed cell migration and invasion via attenuating CCL2 production. The production of CCL2 was modulated by Akt-dependent NF-κB activation that was decreased after rVP1 treatment. The in vivo antitumor effects of rVP1 were assessed in both subcutaneous and orthotopic mouse models of HCC in immune-competent BALB/c mice. Intratumoral delivery of rVP1 inhibited subcutaneous tumor growth as a result of increased apoptosis. Intravenous administration of rVP1 in an orthotopic HCC model suppressed tumor growth, inhibited intra-hepatic metastasis, and prolonged survival. Furthermore, a decrease in the serum level of CCL2 was observed in rVP1-treated mice. CONCLUSIONS/SIGNIFICANCE: The data presented herein suggest that, via inhibiting Akt phosphorylation, rVP1 suppresses the growth, migration, and invasion of murine HCC cells by inducing apoptosis and attenuating CCL2 production both in vitro and in vivo. Recombinant protein VP1 thus has the potential to be developed as a new therapeutic agent for HCC.

  18. UV absorption cross sections of nitrous oxide (N2O and carbon tetrachloride (CCl4 between 210 and 350 K and the atmospheric implications

    Directory of Open Access Journals (Sweden)

    C. H. Jackman

    2010-07-01

    Full Text Available Absorption cross sections of nitrous oxide (N2O and carbon tetrachloride (CCl4 are reported at five atomic UV lines (184.95, 202.548, 206.200, 213.857, and 228.8 nm at temperatures in the range 210–350 K. In addition, UV absorption spectra of CCl4 are reported between 200–235 nm as a function of temperature (225–350 K. The results from this work are critically compared with results from earlier studies. For N2O, the present results are in good agreement with the current JPL recommendation enabling a reduction in the estimated uncertainty in the N2O atmospheric photolysis rate. For CCl4, the present cross section results are systematically greater than the current recommendation at the reduced temperatures most relevant to stratospheric photolysis. The new cross sections result in a 5–7% increase in the modeled CCl4 photolysis loss, and a slight decrease in the stratospheric lifetime, from 51 to 50 years, for present day conditions. The corresponding changes in modeled inorganic chlorine and ozone in the stratosphere are quite small. A CCl4 cross section parameterization for use in atmospheric model calculations is presented.

  19. UV absorption cross sections of nitrous oxide (N2O and carbon tetrachloride (CCl4 between 210 and 350 K and the atmospheric implications

    Directory of Open Access Journals (Sweden)

    C. H. Jackman

    2010-04-01

    Full Text Available Absorption cross sections of nitrous oxide (N2O and carbon tetrachloride (CCl4 are reported at five atomic UV lines (184.95, 202.548, 206.200, 213.857, and 228.8 nm at temperatures in the range 210–350 K. In addition, UV absorption spectra of CCl4 are reported between 200–235 nm as a function of temperature (225–350 K. The results from this work are critically compared with results from earlier studies. For N2O, the present results are in good agreement with the current JPL recommendation enabling a reduction in the estimated uncertainty in the N2O atmospheric photolysis rate. For CCl4, the present cross section results are systematically greater than the current recommendation at the reduced temperatures most relevant to stratospheric photolysis. The new cross sections result in a 5–7% increase in the modeled CCl4 photolysis loss, and a slight decrease in the stratospheric lifetime, from 51 to 50 years, for present day conditions. The corresponding changes in modeled inorganic chlorine and ozone in the stratosphere are quite small. A CCl4 cross section parameterization for use in atmospheric model calculations is presented.

  20. Effect of 3 amino 1,2,4 triazole administration on the early CCl4-induced ultrastructural alterations in rat liver.

    Science.gov (United States)

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; de Fenos, O. M.; Castro, J. A.

    1982-01-01

    CCl4 administration to rats caused at 3 and 6 h intense effects on the liver-cell endoplasmic reticulum such as dilatation, disorganization, detachment of ribosomes, development of extensive areas of smooth component (SER) and formation of myelin figures. 3 Amino 1,2,4 triazole administration (AT) at 3 and 6 h led to the formation of round small vesicles from the rough endoplasmic reticulum (RER), detachment of ribosomes, appearance of extensive areas of SER, appearance of elongated and distorted mitochondria with an increase in the number of peroxisomes. The administration of CCl4 to AT-pretreated animals led to a mutual cancellation of the effects on the RER, particularly remarkable at 3 h but still evident at 6 h; also, the formation of myelin figures was prevented. The other effects on cell ultrastructure exerted either by CCl4 or by AT were also observed with the combination of both chemicals. These observations reinforce the hypothesis about the need of either covalent binding of CCl4 metabolites to cellular constituents or lipid peroxidation, or both, in the origin of CCl4-induced alterations. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:7066182

  1. Fucoidan inhibits CCL22 production through NF-κB pathway in M2 macrophages: a potential therapeutic strategy for cancer

    Science.gov (United States)

    Sun, Jia; Sun, Jintang; Song, Bingfeng; Zhang, Lin; Shao, Qianqian; Liu, Yanguo; Yuan, Daoying; Zhang, Yun; Qu, Xun

    2016-01-01

    In tumor microenvironment, macrophages as a polarized M2 population promote tumor progression via releasing multiple cytokines and chemokines. A brown seaweed fucose-rich polysaccharide, fucoidan has antitumor activity and immune modulation through affecting tumor cells and lymphocytes. Here, we focused on the effect of fucoidan on macrophages especially M2 subtype. Our results demonstrated that fucoidan down-regulated partial cytokines and chemokines, especially a M2-type chemokine CCL22. Furthermore, fucoidan inhibited tumor cells migration and CD4+ T lymphocytes, especially Treg cells, recruitment induced by M2 macrophages conditioned medium through suppression of CCL22. Mechanismly, fucoidan inhibited CCL22 via suppressing p65-NF-κB phosphorylation and nuclear translocation. In addition, p38-MAPK and PI3K-AKT also affected the expression of CCL22 through differential modulation of NF-κB transcriptional activity. Taken together, we reveal an interesting result that fucoidan can inhibit tumor cell migration and lymphocytes recruitment by suppressing CCL22 in M2 macrophages via NF-κB-dependent transcription, which may be a novel and promising mechanism for tumor immunotherapy. PMID:27775051

  2. Suppressive effects of 17β-estradiol on hepatic fibrosis in CCl4-induced rat model

    Institute of Scientific and Technical Information of China (English)

    Qing-Hua Liu; Ding-Guo Li; Xin Huang; Chun-Hua Zong; Qin-Fang Xu; Han-Ming Lu

    2004-01-01

    AIM: To investigate the pathway via which 17β-estradiol (β-Est) exerts suppressive effects on rat hepatic fibrosis.METHODS: In vivo study was done in CCl4-induced female hepatofibrotic rats. Fibrosis-suppressive effect of β-Est rat models. Six weeks after the treatment, all the rats were sacrificed and specimens of serum or liver tissue were collected for the studies. Serum liver enzymes,fibrosis markers and estradiol levels were determined by standard enzymatic methods, ELISA and RIA, respectively.Degrees of fibrosis and areas of hepatic stellate cells (HSCs) positive for alpha-smooth muscle actin (α-SMA) in the liver were determined by van Gieson (VG) stain and immunohistochemistry.In vitro studies, HSCs were isolated by a combination of pronase-collagenase perfusion and density gradient centrifugation. First-passage HSCs were randomly divided into 10 groups, and different concentrations of β-Est, 2-hydroxyestradiol (2OHE) or 2-methoxyestradiol (2MeOE) were separately added to the cell groups. After incubation for 72 h, the degree of cell proliferation, collagen production, α-SMA or estrogen receptor (ER) expression was determined by MTT assay, ELISA and immunohistochemistry,respectively.RESULTS: β-Est treatment reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA) and type Ⅳ collagen (C Ⅳ) in sera, suppressed hepatic collagen content, decreased the areas of HSCs positive for α-SMA significantly in both intact and ovariectomized female hepatofibrotic rats. There was a negative correlation between the percentage of fibrotic area of liver tissue and the serum estradiol level; the calculated correlation coefficient was -0.57 (P<0.01). β-Est and its metabolites concentration-dependently (10-9 mol/L-10-7 mol/L) inhibited HSC proliferation and collagen synthesis. At the concentration of 10-7 mol/L, they could inhibit α-SMA expression. The order of potency was 2MeOE>2OHE>β-Est.CONCLUSION: β-Est may suppress

  3. Hepatoprotective and antioxidant properties of marine halophyte Luminetzera racemosa bark extract in CCL4 induced hepatotoxicity

    Institute of Scientific and Technical Information of China (English)

    MurugesanGnanadesigan; SundaramRavikumar; SamuelJacobInbaneson

    2011-01-01

    Objective:To identify the hepatoprotective and antioxidant activity of Luminetzera racemosa (L. racemosa )bark extract. Methods:Wistar albino rats were divided into 6 groups:Group 1 served as control;Group 2 served as hepatotoxin (CCL4 treated) group;Group 3 served as positive control (Silymarin) treated groups;Group 4, 5 and 6 served as (100, 200 and 300 mg/kg bw p.o.) L. racemosa bark extract treated groups. Moreover, in vitro antioxidant indexes, including DPPH, hydroxyl radical scavenging activity (HRSA), NO, ferric reducing antioxidant power (FRAP), lipid hydroperoxide (LPO) and super oxide dismutase (SOD) were also analyzed in the bark extract. Results:The results suggested that, the level of serum glutamate oxyloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatise (ALP), bilurubin, cholesterol, sugar and lactate dehydrogenase (LDH) were significantly (P<0.05) increased in hepatotoxin treated rats when compared with the control group. But, the maximum reduction of SGOT [(225.36±13.65) IU/L], SGPT [(96.85±17.36) IU/L], ALP [(315.37±17.16) IU/L], bilirubin [(2.97±0.46) mg/dL], cholesterol [(163.73±17.54) mg/dL], sugar [(127.35±27.35) mg/dL] and LDH [(1 784.00±268.36) IU/L] were observed with 300 mg/kg bw of bark extract treated rats. Histopathological scores showed that, no visible changes were observed with high dose (300 mg/kg bw) of bark extract treated rats except mild fatty changes. The in vitro antioxidant assays showed that, the IC50 values were observed as (44.17±6.87)μg/mL, (42.45±2.81)μg/mL, (62.37±3.98)μg/mL, (54.24±3.09)μg/mL, (87.25±5.90)μg/mL and (71.54±5.42)μg/mL for DPPH, HRSA, NO, FRAP, LPO and SOD radical scavenging activities, respectively. Conclusions:The hepatoprotective and antioxidant activities of the bark extract might be to the presence of unique chemical classes such as flavonoids, alkaloids and polyphenols.

  4. Laboratory Building.

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, Joshua M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-03-01

    This report is an analysis of the means of egress and life safety requirements for the laboratory building. The building is located at Sandia National Laboratories (SNL) in Albuquerque, NM. The report includes a prescriptive-based analysis as well as a performance-based analysis. Following the analysis are appendices which contain maps of the laboratory building used throughout the analysis. The top of all the maps is assumed to be north.

  5. Dynamics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Dynamics Lab replicates vibration environments for every Navy platform. Testing performed includes: Flight Clearance, Component Improvement, Qualification, Life...

  6. Chemistry Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: To conduct fundamental studies of highway materials aimed at understanding both failure mechanisms and superior performance. New standard test methods are...

  7. Montlake Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The NWFSC conducts critical fisheries science research at its headquarters in Seattle, WA and at five research stations throughout Washington and Oregon. The unique...

  8. Visualization Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Evaluates and improves the operational effectiveness of existing and emerging electronic warfare systems. By analyzing and visualizing simulation results...

  9. Association of FCGR2A p.R131H and CCL2 c.-2518 A>G gene variants with thrombocytopenia in patients with dengue virus infection.

    Science.gov (United States)

    Alagarasu, Kalichamy; Bachal, Rupali V; Damle, Indraneel; Shah, Paresh S; Cecilia, Dayaraj

    2015-11-01

    FCGR2A and CCL2 gene variants are important in dengue pathogenesis and were investigated in 122 dengue patients (DENs) [89 dengue fever (DF) and 33 dengue hemorrhagic fever (DHF)] and 107 healthy controls (HCs) to find out their association with severity of dengue. Genotype frequencies of FCGR2A p.R131H and CCL2 c.-2518 A > G polymorphisms were not different between DF, DHF and HC. Significantly higher frequency of R/R genotype of FCGR2A p.R131H was observed in DEN cases with thrombocytopenia (TP) while the G/G genotype of CCL2 c.-2518 A > G was observed only in DEN cases with TP (p dengue infections.

  10. CCL2, but not its receptor, is essential to restrict immune privileged central nervous system-invasion of Japanese encephalitis virus via regulating accumulation of CD11b(+) Ly-6C(hi) monocytes.

    Science.gov (United States)

    Kim, Jin Hyoung; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebileg; Hossain, Ferdaus Mohd Altaf; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis virus (JEV) is a re-emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR2-CCL2 axis plays an important role in trafficking CD11b(+) Ly-6C(hi) monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV infection. Here, we explored the role of CCR2 and its ligand CCL2 in JE caused by JEV infection using CCR2- and CCL2-ablated murine models. Somewhat surprisingly, the ablation of CCR2 and CCL2 resulted in starkly contrasting susceptibility to JE. CCR2 ablation induced enhanced resistance to JE, whereas CCL2 ablation highly increased susceptibility to JE. This contrasting regulation of JE progression by CCR2 and CCL2 was coupled to central nervous system (CNS) infiltration of Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. There was also enhanced expression of CC and CXC chemokines in the CNS of CCL2-ablated mice, which appeared to induce CNS infiltration of these cell populations. However, our data revealed that contrasting regulation of JE in CCR2- and CCL2-ablated mice was unlikely to be mediated by innate natural killer and adaptive T-cell responses. Furthermore, CCL2 produced by haematopoietic stem cell-derived leucocytes played a dominant role in CNS accumulation of Ly-6C(hi) monocytes in infected bone marrow chimeric models, thereby exacerbating JE progression. Collectively, our data indicate that CCL2 plays an essential role in conferring protection against JE caused by JEV infection. In addition, blockage of CCR2, but not CCL2, will aid in the development of strategies for prophylactics and therapeutics of JE.

  11. Brucella invasion of human intestinal epithelial cells elicits a weak proinflammatory response but a significant CCL20 secretion.

    Science.gov (United States)

    Ferrero, Mariana C; Fossati, Carlos A; Rumbo, Martín; Baldi, Pablo C

    2012-10-01

    In spite of the frequent acquisition of Brucella infection by the oral route in humans, the interaction of the bacterium with cells of the intestinal mucosa has been poorly studied. Here, we show that different Brucella species can invade human colonic epithelial cell lines (Caco-2 and HT-29), in which only smooth species can replicate efficiently. Infection with smooth strains did not produce a significant cytotoxicity, while the rough strain RB51 was more cytotoxic. Infection of Caco-2 cells or HT-29 cells with either smooth or rough strains of Brucella did not result in an increased secretion of TNF-α, IL-1β, MCP-1, IL-10 or TGF-β as compared with uninfected controls, whereas all the infections induced the secretion of IL-8 and CCL20 by both cell types. The MCP-1 response to flagellin from Salmonella typhimurium was similar in Brucella-infected or uninfected cells, ruling out a bacterial inhibitory mechanism as a reason for the weak proinflammatory response. Infection did not modify ICAM-1 expression levels in Caco-2 cells, but increased them in HT-29 cells. These results suggest that Brucella induces only a weak proinflammatory response in gut epithelial cells, but produces a significant CCL20 secretion. The latter may be important for bacterial dissemination given the known ability of Brucella to survive in dendritic cells.

  12. Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal Ccl2/Ccr2-Dependent Manner.

    Science.gov (United States)

    Kawano, Yoshinaga; Nakae, Jun; Watanabe, Nobuyuki; Kikuchi, Tetsuhiro; Tateya, Sanshiro; Tamori, Yoshikazu; Kaneko, Mari; Abe, Takaya; Onodera, Masafumi; Itoh, Hiroshi

    2016-08-01

    High-fat diet (HFD) induces low-grade chronic inflammation and insulin resistance. However, little is known about the mechanism underlying HFD-induced chronic inflammation in peripheral insulin-responsive tissues. Here, we show that colonic pro-inflammatory macrophages regulate insulin sensitivity under HFD conditions. To investigate the pathophysiological role of colonic macrophages, we generated macrophage-specific chemokine (C-C Motif) receptor 2 (Ccr2) knockout (M-Ccr2KO) and intestinal epithelial cell-specific tamoxifen-inducible Ccl2 knockout (Vil-Ccl2KO) mice. Both strains exhibited similar body weight to control under HFD. However, they exhibited decreased infiltration of colonic pro-inflammatory macrophages, decreased intestinal permeability, and inactivation of the colonic inflammasome. Interestingly, they showed significantly improved glucose tolerance and insulin sensitivity with decreased chronic inflammation of adipose tissue. Therefore, inhibition of pro-inflammatory macrophage infiltration prevents HFD-induced insulin resistance and could be a novel therapeutic approach for type 2 diabetes. PMID:27508875

  13. Accelerated CCl4-induced liver fibrosis in Hjv-/- mice, associated with an oxidative burst and precocious profibrogenic gene expression.

    Directory of Open Access Journals (Sweden)

    Giada Sebastiani

    Full Text Available Hereditary hemochromatosis is commonly associated with liver fibrosis. Likewise, hepatic iron overload secondary to chronic liver diseases aggravates liver injury. To uncover underlying molecular mechanisms, hemochromatotic hemojuvelin knockout (Hjv-/- mice and wild type (wt controls were intoxicated with CCl(4. Hjv-/- mice developed earlier (by 2-4 weeks and more acute liver damage, reflected in dramatic levels of serum transaminases and ferritin and the development of severe coagulative necrosis and fibrosis. These responses were associated with an oxidative burst and early upregulation of mRNAs encoding α1-(I-collagen, the profibrogenic cytokines TGF-β1, endothelin-1 and PDGF and, notably, the iron-regulatory hormone hepcidin. Hence, CCl4-induced liver fibrogenesis was exacerbated and progressed precociously in Hjv-/- animals. Even though livers of naïve Hjv-/- mice were devoid of apparent pathology, they exhibited oxidative stress and immunoreactivity towards α-SMA antibodies, a marker of hepatic stellate cells activation. Furthermore, they expressed significantly higher (2-3 fold vs. wt, p<0.05 levels of α1-(I-collagen, TGF-β1, endothelin-1 and PDGF mRNAs, indicative of early fibrogenesis. Our data suggest that hepatic iron overload in parenchymal cells promotes oxidative stress and triggers premature profibrogenic gene expression, contributing to accelerated onset and precipitous progression of liver fibrogenesis.

  14. Learning Laboratory.

    Science.gov (United States)

    Hay, Lyn; Callison, Daniel

    2000-01-01

    Considers the school library media center as an information learning laboratory. Topics include information literacy; Kuhlthau's Information Search Process model; inquiry theory and approach; discovery learning; process skills of laboratory science; the information scientist; attitudes of media specialists, teachers, and students; displays and Web…

  15. Characterization of copy number variants for CCL3L1 gene in rheumatoid arthritis for French trio families and Tunisian cases and controls.

    Science.gov (United States)

    Ben Kilani, Mohamed Sahbi; Achour, Yosser; Perea, Javier; Cornelis, François; Bardin, Thomas; Chaudru, Valérie; Maalej, Abdellatif; Petit-Teixeira, Elisabeth

    2016-08-01

    Analyses of copy number variants (CNVs) for candidate genes in complex diseases are currently a promising research field. CNVs of C-C chemokine ligand 3-like 1 (CCL3L1) gene are candidate genomic factors in rheumatoid arthritis (RA). We investigated CCL3L1 CNVs association with a case-control study in Tunisians and a transmission analysis in French trio families. Relative copy number (rCN) of CCL3L1 gene was quantified by droplet digital PCR (ddPCR) in 100 French trio families (RA patients and their two parents) and in 166 RA cases and 102 healthy controls from Tunisia. We calculated odds ratio (OR) to investigate association risk for CCL3L1 CNVs in RA. rCN identified varied from 0 to 4 in the French population and from 0 to 7 in the Tunisian population. A significant difference was observed in the distribution of these rCNs between the two populations (p = 2.34 × 10(-10)), as when rCN from French and Tunisian RA patients were compared (p = 2.83 × 10(-5)). CNVs transmission in French RA trios allowed the characterization of genotypes with the presence of tandem duplication and triplication on the same chromosome. RA association tests highlighted a protective effect of rCN = 5 for CCL3L1 gene in the Tunisian population (OR = 0.056; CI 95 % [0.01-0.46]). Characterization of CCL3L1 CNVs with ddPCR methodology highlighted specific CN genotypes in a French family sample. A copy number polymorphism of a RA candidate gene was quantified, and its significant association with RA was revealed in a Tunisian sample.

  16. Variants of C-C motif chemokine 22 (CCL22 are associated with susceptibility to atopic dermatitis: case-control studies.

    Directory of Open Access Journals (Sweden)

    Tomomitsu Hirota

    Full Text Available Atopic dermatitis (AD is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2 cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1(st population, 916 cases and 1,032 controls; 2(nd population 1,034 cases and 1,004 controls. After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10⁻⁶; OR, 0.74; 95% CI, 0.65-0.85. Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD.

  17. Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis: case-control studies.

    Science.gov (United States)

    Hirota, Tomomitsu; Saeki, Hidehisa; Tomita, Kaori; Tanaka, Shota; Ebe, Kouji; Sakashita, Masafumi; Yamada, Takechiyo; Fujieda, Shigeharu; Miyatake, Akihiko; Doi, Satoru; Enomoto, Tadao; Hizawa, Nobuyuki; Sakamoto, Tohru; Masuko, Hironori; Sasaki, Takashi; Ebihara, Tamotsu; Amagai, Masayuki; Esaki, Hitokazu; Takeuchi, Satoshi; Furue, Masutaka; Noguchi, Emiko; Kamatani, Naoyuki; Nakamura, Yusuke; Kubo, Michiaki; Tamari, Mayumi

    2011-01-01

    Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1(st) population, 916 cases and 1,032 controls; 2(nd) population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10⁻⁶; OR, 0.74; 95% CI, 0.65-0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD.

  18. Comparative Study of Circulating MMP-7, CCL18, KL-6, SP-A, and SP-D as Disease Markers of Idiopathic Pulmonary Fibrosis

    OpenAIRE

    Hamai, Kosuke; Iwamoto, Hiroshi; Ishikawa, Nobuhisa; Horimasu, Yasushi; Masuda, Takeshi; Miyamoto, Shintaro; Nakashima, Taku; Ohshimo, Shinichiro; Fujitaka, Kazunori; Hamada, Hironobu; Hattori, Noboru; Kohno, Nobuoki

    2016-01-01

    Background. Recent reports indicate that matrix metalloproteinase-7 (MMP-7) and CC-chemokine ligand 18 (CCL18) are potential disease markers of idiopathic pulmonary fibrosis (IPF). The objective of this study was to perform direct comparisons of these two biomarkers with three well-investigated serum markers of IPF, Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), and SP-D. Methods. The serum levels of MMP-7, CCL18, KL-6, SP-A, and SP-D were evaluated in 65 patients with IPF, 31 pa...

  19. The fate of atmospheric phosgene and the stratospheric chlorine loadings of its parent compounds: CCl4, C2Cl4, C2HCL3, CH3CCl3, and CHCl3

    Science.gov (United States)

    Kindler, T. P.; Chameides, W. L.; Wine, P. H.; Cunnold, D. M.; Alyea, F. N.; Franklin, J. A.

    1995-01-01

    A study of the tropospheric and stratospheric cycles of phosgene is carried out to determine its fate and ultimate role in controlling the ozone depletion potentials of its parent compounds. Tropospheric phosgene is produced from the OH-initiated oxidation of C2Cl4, CH3CCl3, CHCl3, and C2HCl3. Simulations using a two-dimensional model indicate that these processes produce about 90 pptv/yr of tropospheric phosgene with an average concentration of about 18 pptv, in reasonable agreement with observations. We estimate a residence time of about 70 days for tropospheric phosgene, with the vast majority being removed by hydrolysis in cloudwater. Only about 0.4% of the phosgene produced in the troposphere avoids wet removal and is transported to the stratosphere, where its chlorine can be released to participate in the catalytic destruction of ozone. Stratospheric phosgene is produced from the photochemical degradation of CCl4, C2Cl4, CHCl3, and CH3CCl3 and is removed by photolysis and downward transport to the troposphere. Model calculations, in good agreement with observations, indicate that these processes produce a peak stratospheric concentration of about 25-30 pptv at an altitude of about 25 km. In contrast to tropospheric phosgene, stratospheric phosgene is found to have a lifetime against photochemical removal of the order of years. As a result, a significant portion of the phosgene that is produced in the stratosphere is ultimately returned to the troposphere, where it is rapidly removed by clouds. This phenomenon effectively decreases the amount of reactive chlorine injected into the stratosphere and available for ozone depletion from phosgene's parent compounds. A similar phenomenon due to the downward transport of stratospheric COFCl produced from CFC-11 is estimated to cause a 7% decrease in the amount of reactive chlorine injected into the stratosphere from this compound. Our results are potentially sensitive to a variety of parameters, most notably the rate

  20. 苯巴比妥联合 CCl4法建立肝硬化腹水大鼠模型%To establish the model of cirrhotic rats with ascites phenobarbital combined with CCl4 method

    Institute of Scientific and Technical Information of China (English)

    方庆; 王成业; 姚瑶; 王满媛; 许钒

    2015-01-01

    Objective To establish a stable rat model of liver cirrhosis by using carbon tetrachloride combined with Phenobarbital Sodi-um.Methods 35%Phenobarbital Sodium was carried out in SD rats for 7 days to activate hepatic microsomal enzyme P450.From the second week,gradient carbon tetrachloride oil solution was offered by intraperitoneal injection (twice per week for 14 weeks).24 h u-rine of rats was collected and measured at the end time of the trial.HE staining of liver tissue was used to observe pathological process of liver.Results After induced with Phenobarbital Sodium for 7 days and then injected with carbon tetrachloride into abdominal cavity continuously for 13 weeks,a stable rat model of liver cirrhosis could be achieved.Conclusion The procedure is stable and reliable for building liver cirrhosis model,and the model has lower mortality and shorter cycle time than traditional one.%目的:采用苯巴比妥联合四氯化碳构建稳定的肝硬化腹水大鼠模型,为抗肝硬化腹水药物的研究提供有效可靠的动物模型。方法采用苯巴比妥联合CCl4法复制肝硬化腹水大鼠模型。35%苯巴比妥溶液诱导1周,激活肝脏肝药酶P450活性,第二周开始,按梯度腹腔注射CCl4油溶液,每周2次至第14周。实验进行至中后期,收集大鼠24 h尿液,测量尿量;检查腹腔积液量;肝组织HE染色观察肝脏病理进程。结果大鼠经苯巴比妥溶液诱导1周后,连续腹腔注射CCl4油溶液13周,可复制稳定的肝硬化腹水模型。结论该法可建立稳定、可靠的肝硬化腹水模型,比传统模型降低了死亡率,且造模时间缩短。

  1. Co-delivery of ccl19 gene enhances anti-caries DNA vaccine pCIA-P immunogenicity in mice by increasing dendritic cell migration to secondary lymphoid tissues

    Institute of Scientific and Technical Information of China (English)

    Yan-hong YAN; Sheng-cai QI; Ling-kai SU; Qing-an XU; Ming-wen FAN

    2013-01-01

    Aim:To investigate how co-delivery of the gene encoding C-C chemokine ligand-19 (CCL-19) affected the systemic immune responses to an anti-caries DNA vaccine pClA-P in mice.Methods:Plasmid encoding CCL19-GFP fusion protein (pCCL19/GFP) was constructed by inserting murine ccl19 gene into GFPexpressing vector pAcGFP1-N1.Chemotactic effect of the fusion protein on murine dendritic cells (DCs) was assessed in vitro and in vivo using transwell and flow cytometric analysis,respectively.BALB/c mice were administered anti-caries DNA vaccine pClA-P plus pCCL19/GFP (each 100 μg,im) or pClA-P alone.Serum level of anti-PAc IgG was assessed with ELISA.Splenocytes from the mice were stimulated with PAc protein for 48 h,and IFN-y and IL-4 production was measured with ELISA.The presence of pCCL19/GFP in spleen and draining lymph nodes was assessed using PCR.The expression of pCCL19/GFP protein in these tissues was analyzed under microscope and with flow cytometry.Results:The expression level of CCL19-GFP fusion protein was considerably increased 48 h after transfection of C0S-7 cells with pCCL19/GFP plasmids.The fusion protein showed potent chemotactic activity on DCs in vitro.The level of serum PAc-specific IgG was significantly increased from 4 to 14 weeks in the mice vaccinated with pCIA-P plus pCCL19/GFP.Compared to mice vaccinated with pCIA-P alone,the splenocytes from mice vaccinated with pClA-P plus pCCL19/GFP produced significantly higher level of IFN-Y,but IL-4 production had no significant change.Following intromuscular co-delivery,pCCL19/GFP plasmid and fusion protein were detected in the spleen and draining lymph nodes.Administration of CCL19 gene in mice markedly increased the number of mature DCs in secondary lymphoid tissues.Conclusion:CCL19 serves as an effective adjuvant for anti-caries DNA vaccine by inducing chemotactic migration of DCs to secondary lymphoid tissues.

  2. 131I治疗前后Graves病患者CXCL10、CCL22水平表达变化的研究%Changes of CXCL10 and CCL22 in patients with Graves' disease after radioactive iodine therapy

    Institute of Scientific and Technical Information of China (English)

    谭淑君; 李春北; 李铭

    2014-01-01

    Objective To detect the changes of CXCL10 and CCL22 in patients with Graves' disease (GD) after radioactive iodine therapy. Methods Forty-six patients with GD were enrolled into our study (GD group). An-other 40 healthy people were used as normal controls (control group). CXCL10 and CCL22 were detected by ELIAS. Th1 and Th2 cells was detected by flow cytometry. Results The expression levels of CXCL10 and CCL22 was (16.8±6.3) ng/L and (150.4±22.6) ng/L in control group, (62.4±13.2) ng/L and (161.3±25.4) ng/L in GD group (P0.05)。两组之间CXCL10/CCL22比值差异也有统计学意义(P0.05)。两组之间Th1/Th2比值差异也有统计学意义(P<0.05)。结论 Graves病患者中存在CXCL10和CCL22表达水平的升高,131I治疗后可降低CXCL10和CCL22表达水平,调节Th1/Th2细胞的失衡,CXCL10和CCL22因子的检测有可能作为131I治疗反应性的一个指标。

  3. TLR4、CCL5、CCR5在尖锐湿疣皮损中的表达及意义%THE SIGNIFICANCE AND EXPRESSION CHARACTERISTICS OF TLR 4、 CCL5 AND CCR5 IN THE LESIONS OF PATIENTS WITH CONDYLOMA ACUMINATUM

    Institute of Scientific and Technical Information of China (English)

    毛广宇; 刘志芳

    2011-01-01

    Objective:To discuss the effect of the TLR4,CCL5 and CCR5 in the HPV immune escape progress, and enrich the theory of immune escape. Methord: Using the immunohistochemisty, probe the expression of 50 cases of condyloma acuminatum and 10 cases of normal skin. Results:The expression of TLR4 、CCL5 and CCR5 in the lesions of patients with condyloma acuminatum is significantly higher than that in normal foreskins(P < 0. 05 ). Conclusion: TLR4, CCL5 and CCR5 play an important role in the progress of the immunoreaction which aim at the human papilloma virus.%目的:探讨Toll样受体4(TLR4)、趋化因子CCL5及其受体CCR5在尖锐湿疣局部皮损中的表达特性及可能的生物学意义,以期发现它们在HPV免疫逃逸过程中所起到的作用.方法:采用免疫组化SABC法检测TLR4、CCL5、CCR5在尖锐湿疣局部皮损(50例)及正常皮肤对照组(10例)中的表达情况.结果:TLR4、CCL5、CCR5在尖锐湿疣皮损中的表达情况明显高于正常皮肤对照组(P<0.05).结论:TLR4、CCL5、CCR5可能在机体对抗HPV的免疫过程中起一定作用.

  4. Laboratory Tests

    Science.gov (United States)

    ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & ... or conditions. What are lab tests? Laboratory tests are medical procedures that involve testing samples of blood, urine, or other tissues or ...

  5. Tumor-derived CCL-2 and CXCL-8 as possible prognostic markers of breast cancer: correlation with estrogen and progestrone receptor phenotyping.

    Science.gov (United States)

    Ghoneim, H M; Maher, Sara; Abdel-Aty, Asmaa; Saad, A; Kazem, A; Demian, S R

    2009-01-01

    Prognosis of breast cancer is believed to be a multifactorial process best achieved by complex factors including host and tumor-derived biomarkers together with traditional clinicopathological parameters and tumor histologic markers. The present study aimed at evaluating the prognostic significance of chemokine ligand-2 (CCL-2) and interleukin-8 (CXCL-8) expression in extracts of breast carcinomas through correlation with clinicopathological aspects as well as estrogen receptor (ER) and progesterone receptor (PR) phenotyping. The study was conducted on 30 Egyptian breast cancer patients diagnosed by fine needle aspiration cytology (FNAC) and subjected to modified radical mastectomy. Excised tissues were used to prepare tissue sections and extracts for histopathological and immunohistochemical studies. Expression of CCL-2 and CXCL-8 was determined by enzyme-linked immunosorbent assay (ELISA). 26 patients had invasive ductal carcinoma, grades II and III with metastasis to axillary lymph nodes and ER and PR positive phenotype. Expression of CCL-2 and CXCL-8 was significantly influenced by patient's age, menopausal status, nodal involvement, tumor grade and the ER phenotype. In contrast, it was not affected by either tumor size or PR staining pattern. Both chemokines correlated positively to each other and to tumor grade and negatively to age, menopausal status of patients and ER phenotyping. It is concluded that the angiogenic chemokine CXCL-8 and the macrophage chemoattractant CCL-2 might be useful prognostic markers where their routine follow up might be of importance in assessment of tumor aggressiveness in clinical settings. PMID:22059352

  6. Highly potent HIV inhibition: engineering a key anti-HIV structure from PSC-RANTES into MIP-1 beta/CCL4.

    Science.gov (United States)

    Gaertner, Hubert; Lebeau, Olivier; Borlat, Irène; Cerini, Fabrice; Dufour, Brigitte; Kuenzi, Gabriel; Melotti, Astrid; Fish, Richard J; Offord, Robin; Springael, Jean-Yves; Parmentier, Marc; Hartley, Oliver

    2008-02-01

    The HIV coreceptor CCR5 is a validated target for both the prevention and therapy of HIV infection. PSC-RANTES, an N-terminally modified analogue of one of the natural chemokine ligands of CCR5 (RANTES/CCL5), is a potent inhibitor of HIV entry into target cells. Here, we set out to engineer the anti-HIV activity of PSC-RANTES into another natural CCR5 ligand (MIP-1beta/CCL4), by grafting into it the key N-terminal pharmacophore region from PSC-RANTES. We were able to identify MIP-1beta/CCL4 analogues that retain the receptor binding profile of MIP-1beta/CCL4, but acquire the very high anti-HIV potency and characteristic inhibitory mechanism of PSC-RANTES. Unexpectedly, we discovered that in addition to N-terminal structures from PSC-RANTES, the side chain of Lys33 is also necessary for full anti-HIV potency.

  7. Evaluation of the Effects of Some Brazilian Medicinal Plants on the Production of TNF-α and CCL2 by THP-1 Cells

    Directory of Open Access Journals (Sweden)

    Grasielle S. Gusman

    2015-01-01

    Full Text Available Several plant species are traditionally used in Brazil to treat various inflammatory diseases. Tumor necrosis factor- (TNF- α and chemokine (C-C motif ligand 2 (CCL2 are key inflammatory mediators in diseases like rheumatoid arthritis and atherosclerosis, respectively; nevertheless, only a few extracts have been assayed against these targets. We herein report the effect of 19 plant extracts on TNF-α and CCL2 release by lipopolysaccharide- (LPS- stimulated THP-1 cells, a human monocytic leukemia cell line, along with their radical scavenging activity on DPPH. The extracts of Caryocar brasiliense, Casearia sylvestris, Coccoloba cereifera, and Terminalia glabrescens inhibited TNF-α production in a concentration-dependent manner. Fractionation of these extracts potentiated the anti-TNF-α effect, which was shown to concentrate in polar fractions, mainly composed by polyphenols. Significant CCL2 inhibition was elicited by Lippia sidoides and Terminalia glabrescens extracts, whose fractionation resulted in highly active low polar fractions. All assayed extracts showed strong radical scavenging activity, but antioxidant activity did not correlate with inhibition of TNF-α or CCL2 production. Our results allowed identifying extracts with selective capacity to block cytokine production; therefore, further purification of these extracts may yield molecules that could be useful in the treatment of chronic inflammatory diseases.

  8. Effect of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of certain plasma enzymes in CCl4-induced liver injury in low-protein fed rats.

    Science.gov (United States)

    Nkosi, C Z; Opoku, A R; Terblanche, S E

    2005-04-01

    The effects of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of lactate dehydrogenase (LD), alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) against carbon tetrachloride (CCl4)-induced acute liver injury in low-protein fed rats were investigated. A group of male Sprague-Dawley rats maintained on a low-protein diet for 5 days were divided into three subgroups. Two subgroups were injected with carbon tetrachloride and the other group with an equivalent amount of olive oil. Two hours after CCl4 intoxication one of the two subgroups was administered with pumpkin seed protein isolate. All three subgroups of rats were maintained on the low-protein diet for the duration of the investigation. Groups of rats from the different subgroups were killed at 24, 48 and 72 h after their respective treatments. After 5 days on the low-protein diet the activity levels of all four enzymes were significantly higher than their counterparts on a normal balanced diet. CCl4 intoxication resulted in significant increases in the activity levels of all four enzymes investigated. The administration of pumpkin seed protein isolate after CCl4 intoxication resulted in significantly reduced activity levels of all four enzymes. It is concluded that pumpkin seed protein isolate administration was effective in alleviating the detrimental effects associated with protein malnutrition. PMID:16041732

  9. Tumor-derived CCL-2 and CXCL-8 as possible prognostic markers of breast cancer: correlation with estrogen and progestrone receptor phenotyping.

    Science.gov (United States)

    Ghoneim, H M; Maher, Sara; Abdel-Aty, Asmaa; Saad, A; Kazem, A; Demian, S R

    2009-01-01

    Prognosis of breast cancer is believed to be a multifactorial process best achieved by complex factors including host and tumor-derived biomarkers together with traditional clinicopathological parameters and tumor histologic markers. The present study aimed at evaluating the prognostic significance of chemokine ligand-2 (CCL-2) and interleukin-8 (CXCL-8) expression in extracts of breast carcinomas through correlation with clinicopathological aspects as well as estrogen receptor (ER) and progesterone receptor (PR) phenotyping. The study was conducted on 30 Egyptian breast cancer patients diagnosed by fine needle aspiration cytology (FNAC) and subjected to modified radical mastectomy. Excised tissues were used to prepare tissue sections and extracts for histopathological and immunohistochemical studies. Expression of CCL-2 and CXCL-8 was determined by enzyme-linked immunosorbent assay (ELISA). 26 patients had invasive ductal carcinoma, grades II and III with metastasis to axillary lymph nodes and ER and PR positive phenotype. Expression of CCL-2 and CXCL-8 was significantly influenced by patient's age, menopausal status, nodal involvement, tumor grade and the ER phenotype. In contrast, it was not affected by either tumor size or PR staining pattern. Both chemokines correlated positively to each other and to tumor grade and negatively to age, menopausal status of patients and ER phenotyping. It is concluded that the angiogenic chemokine CXCL-8 and the macrophage chemoattractant CCL-2 might be useful prognostic markers where their routine follow up might be of importance in assessment of tumor aggressiveness in clinical settings.

  10. Essential roles of the interaction between cancer cell-derived chemokine, CCL4, and intra-bone CCR5-expressing fibroblasts in breast cancer bone metastasis.

    Science.gov (United States)

    Sasaki, Soichiro; Baba, Tomohisa; Nishimura, Tatsunori; Hayakawa, Yoshihiro; Hashimoto, Shin-Ichi; Gotoh, Noriko; Mukaida, Naofumi

    2016-08-01

    From a murine breast cancer cell line, 4T1, we established a subclone, 4T1.3, which consistently metastasizes to bone upon its injection into the mammary fat pad. 4T1.3 clone exhibited similar proliferation rate and migration capacity as the parental clone. However, the intra-bone injection of 4T1.3 clone caused larger tumors than that of the parental cells, accompanied with increases in fibroblast, but not osteoclast or osteoblast numbers. 4T1.3 clone displayed an enhanced expression of a chemokine, CCL4, but not its specific receptor, CCR5. CCL4 shRNA-transfection of 4T1.3 clone had few effects on its in vitro properties, but reduced the tumorigenicity arising from the intra-bone injection. Moreover, intra-bone injection of 4T1.3 clone caused smaller tumors in mice deficient in CCR5 or those receiving CCR5 antagonist than in wild-type mice. The reduced tumor formation was associated with attenuated accumulation of CCR5-positive fibroblasts expressing connective tissue growth factor (CTGF)/CCN2. Tumor cell-derived CCL4 could induce fibroblasts to express CTGF/CCN2, which could support 4T1.3 clone proliferation under hypoxic culture conditions. Thus, the CCL4-CCR5 axis can contribute to breast cancer metastasis to bone by mediating the interaction between cancer cells and fibroblasts in bone cavity.

  11. RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

    NARCIS (Netherlands)

    S. Kathiresan (Sekar); M.P. Reilly (Muredach); N.J. Samani (Nilesh); H. Schunkert (Heribert); J. Erdmann (Jeanette); F.L. Moll (Frans); E. Boerwinkle (Eric); A. Hall (Anne); C. Hengstenberg (Christian); I.R. König (Inke); R. Laaksonen (Reijo); R. McPherson (Ruth); J.R. Thompson (John); U. Thorsteinsdottir (Unnur); A. Ziegler; W. Koenig (Wolfgang); L. Chen (Li); L.A. Cupples (Adrienne); E. Halperin (Eran); X. Li (Xiaohui); K. Musunuru (Kiran); M. Preuss (Michael); A. Schillert (Arne); G. Thorleifsson (Gudmar); B.F. Voight (Benjamin); G.A. Wells (George); P. Deloukas (Panagiotis); H. Holm (Hilma); R. Roberts (Robert); A.F.R. Stewart (Alexandre); S.P. Fortmann (Stephen); A. Go (Attie); M.A. Hlatky (Mark); C. Iribarren (Carlos); J.W. Knowles (Joshua); R.H. Myers (Richard); T. Quertermous (Thomas); S. Sidney (Steven); N. Risch; H. Tang (Hui); S. Blankenberg (Stefan); T. Zeller (Tanja); P.S. Wild (Philipp); R.B. Schnabel (Renate); C. Sinning (Christoph); K.J. Lackner (Karl); L. Tiret (Laurence); V. Nicaud; F. Cambien (François); H. Bickel (Horst); H.J. Rupprecht; C. Perret (Claire); C. Proust (Carole); T. Munzel (Thomas); M. Barbalic (maja); J.C. Bis (Joshua); I.Y.-D. Chen (Ida Yii-Der); A. Dehghan (Abbas); S. Demissie-Banjaw (Serkalem); A.R. Folsom (Aaron); N.L. Glazer (Nicole); V. Gudnason (Vilmundur); T.B. Harris (Tamara); S.R. Heckbert (Susan); D. Levy (Daniel); T. Lumley (Thomas); K. Marciante (Kristin); A.C. Morrison (Alanna); C.J. O'Donnell (Christopher); B.M. Psaty (Bruce); K. Rice (Kenneth); J.I. Rotter (Jerome); D.S. Siscovick (David); N.L. Smith (Nicholas); G.D. Smith; K.D. Taylor (Kent); C.M. van Duijn (Cock); K.A. Volcik (Kelly); J. Whitteman (Jaqueline); V.S. Ramachandran (Vasan); A. Hofman (Albert); A.G. Uitterlinden (André); S. Gretarsdottir (Solveig); J.R. Gulcher (Jeffrey); A. Kong (Augustine); J-A. Zwart (John-Anker); G. Thorgeirsson (Gudmundur); K. Andersen (Karl); M. Fischer (Marcus); A. Großhennig (Anika); W. Lieb (Wolfgang); P. Linsel-Nitschke (Patrick); K. Stark (Klaus); S. Schreiber (Stefan); H.E. Wichmann (Heinz Erich); Z. Aherrahrou (Zouhair); P. Bruse (Petra); A. Doering (Angela); T. Illig (Thomas); N. Klopp (Norman); C. Loley (Christina); A. Medack (Anja); C. Meisinger (Christa); T. Meitinger (Thomas); J. Nahrstedt (Janja); A. Peters (Annette); A.K. Wagner (Arnika); C. Willenborg (Christina); B. Böhm; H. Dobnig (Harald); T.B. Grammer (Tanja); M.M. Hoffmann (Michael); M. Kleber (Martina); W. März (Winfried); A. Meinitzer (Andreas); B. Winkelmann; D.T. Pilz (Daniela); W. Renner (Wilfried); H. Scharnagl (Hubert); T. Stojakovic (Tatjana); A. Tomaschitz (Andreas); K. Winkler (Karl); C. Guiducci (Candace); N.P. Burtt (Noël); S.B. Gabriel (Stacey); R. Elosua (Roberto); L. Peltonen (Leena Johanna); V. Salomaa (Veikko); S.M. Schwartz (Stephen); O. Melander (Olle); D. Altshuler (David); S. Dandona (Sonny); O. Jarinova (Olga); L. Qu (Liming); A. Wilensky (Asaf); W. Matthai (William); H. Hakonarson (Hakon); J. Devaney (Joseph); M.S. Burnett; A.D. Pichard; K.M. Kent (Kenneth); L.F. Satler; J.M. Lindsay (Joseph); R. Waksman (Ron); C.W. Knouff (Christopher); D. Waterworth (Dawn); M.C. Walker (Max); V. Mooser (Vincent); S.E. Epstein (Stephen); D.J. Rader (Daniel); P.S. Braund (Peter); C.P. Nelson (Christopher P.); B.J. Wright (Benjamin); A.J. Balmforth (Anthony); S.G. Ball (Stephen)

    2011-01-01

    textabstractBackground: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associat

  12. Essential roles of the interaction between cancer cell-derived chemokine, CCL4, and intra-bone CCR5-expressing fibroblasts in breast cancer bone metastasis.

    Science.gov (United States)

    Sasaki, Soichiro; Baba, Tomohisa; Nishimura, Tatsunori; Hayakawa, Yoshihiro; Hashimoto, Shin-Ichi; Gotoh, Noriko; Mukaida, Naofumi

    2016-08-01

    From a murine breast cancer cell line, 4T1, we established a subclone, 4T1.3, which consistently metastasizes to bone upon its injection into the mammary fat pad. 4T1.3 clone exhibited similar proliferation rate and migration capacity as the parental clone. However, the intra-bone injection of 4T1.3 clone caused larger tumors than that of the parental cells, accompanied with increases in fibroblast, but not osteoclast or osteoblast numbers. 4T1.3 clone displayed an enhanced expression of a chemokine, CCL4, but not its specific receptor, CCR5. CCL4 shRNA-transfection of 4T1.3 clone had few effects on its in vitro properties, but reduced the tumorigenicity arising from the intra-bone injection. Moreover, intra-bone injection of 4T1.3 clone caused smaller tumors in mice deficient in CCR5 or those receiving CCR5 antagonist than in wild-type mice. The reduced tumor formation was associated with attenuated accumulation of CCR5-positive fibroblasts expressing connective tissue growth factor (CTGF)/CCN2. Tumor cell-derived CCL4 could induce fibroblasts to express CTGF/CCN2, which could support 4T1.3 clone proliferation under hypoxic culture conditions. Thus, the CCL4-CCR5 axis can contribute to breast cancer metastasis to bone by mediating the interaction between cancer cells and fibroblasts in bone cavity. PMID:27177471

  13. Quantum yield of Cl∗ (21/2) production in the gas phase photolysis of CCl4 in the ultraviolet

    Indian Academy of Sciences (India)

    Manish Tak; Manabendra Chandra; Dulal Senapati; Puspendu K Das

    2006-07-01

    In this paper, we have probed the dynamics of chlorine atom production from the gas phase photodissociation of carbon tetrachloride at 222 and 235 nm. The quantum yield, * of Cl∗ (21/2) production has been determined by probing the nascent concentrations of both excited (21/2) and ground state (23/2) chlorine atoms by suitable resonance-enhanced multiphoton ionization (REMPI) detection schemes. Although at the photolysis wavelengths the absorption of carbon tetrachloride is weak, significant amounts of Cl∗ are produced. Surprisingly, the quantum yield of Cl∗ production does not follow the absorption spectrum closely, which gives rise to the possibility of an indirect dissociation mechanism present in CCl4 along with direct dissociation at these ultraviolet wavelengths.

  14. Dynamics of intermolecular interactions in CCl4via the isotope effect by femtosecond time-resolved spectroscopy.

    Science.gov (United States)

    Konarska, Jadwiga; Gadomski, Wojciech; Ratajska-Gadomska, Bożena; Polok, Kamil; Pudłowski, Grzegorz; Kardaś, Tomasz M

    2016-06-21

    We report our study on the ultrafast dynamics of intermolecular interactions in liquid CCl4. A transient transmission time domain signal, obtained in the 40 ps delay range, exhibits beating at the difference frequency of the totally symmetric stretching vibrations of the tetrachloride isotopologues. We show that the spectra obtained as the windowed Fourier transform of different parts of the time domain signal in the range of this totally symmetric vibration, split due to the isotope effect, carry the information about the dynamics of the coherently excited, coupled molecules. We use a simple theoretical model in order to prove that the intermolecular interaction influences the relative amplitudes of the isotopologue peaks in the spectrum. Moreover, we demonstrate that the pump induced coherence in the system leads to additional strengthening of the interaction, which can be observed in the spectra obtained from the experimental time domain signal. PMID:27244535

  15. The analgesic effect of rolipram is associated with the inhibition of the activation of the spinal astrocytic JNK/CCL2 pathway in bone cancer pain

    Science.gov (United States)

    Guo, Chi-Hua; Bai, Lu; Wu, Huang-Hui; Yang, Jing; Cai, Guo-Hong; Wang, Xin; Wu, Sheng-Xi; Ma, Wei

    2016-01-01

    Bone cancer pain (BCP) is one of the most difficult and intractable tasks for pain management, which is associated with spinal 'neuron-astrocytic' activation. The activation of the c-Jun N-terminal kinase (JNK)/chemokine (C-C motif) ligand (CCL2) signaling pathway has been reported to be critical for neuropathic pain. Rolipram (ROL), a selective phosphodiesterase 4 inhibitor, possesses potent anti-inflammatory and anti-nociceptive activities. The present study aimed to investigate whether the intrathecal administration of ROL has an analgesic effect on BCP in rats, and to assess whether the inhibition of spinal JNK/CCL2 pathway and astrocytic activation are involved in the analgesic effects of ROL. The analgesic effects of ROL were evaluated using the Von Frey and Hargreaves tests. Immunofluorescence staining was used to determine the number of c-Fos immunoreactive neurons, and the expression of spinal astrocytes and microglial activation on day 14 after tumor cell inoculation. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α] and chemokines (CCL2), and western blot analysis was then used to examine the spinal phosphodiesterase 4 (PDE4), ionized calcium binding adapter molecule-1 (IBA-1) and JNK levels on day 14 after tumor cell inoculation. The results revealed that ROL exerted a short-term analgesic effect in a dose-dependent manner, and consecutive daily injections of ROL exerted continuous analgesic effects. In addition, spinal 'neuron-astrocytic' activation was suppressed and was associated with the downregulation of spinal IL-1β, IL-6 and TNF-α expression, and the inhibition of PDE4B and JNK levels in the spine was also observed. In addition, the level of CCL2 was decreased in the rats with BCP. The JNK inhibitor, SP600125, decreased CCL2 expression and attenuated pain behavior. Following co-treatment with ROL and SP600125, no significant

  16. Effects of Biphenyldimethyl-dicarboxylate Administration Alone or Combined with Silymarin in the CCL4 Model of Liver Fibrosis in Rats

    Directory of Open Access Journals (Sweden)

    Omar M. E. Abdel-Salam

    2007-01-01

    Full Text Available The effect of biphenyldimethyldicarboxylate (DDB, a synthetic compound, in use for the treatment of chronic hepatitis was studied on hepatic injury caused in rats by administration of carbon tetrachloride (CCl4. Starting at time of administration of the first dose of CCl4, rats received DDB at four dose levels (3, 15, 75 or 375 mg/kg, silymarin (22 mg/kg, a combination of DDB (75 mg/kg and silymarin (22 mg/kg or saline (control once orally daily for 30 days. The administration of DDB in CCl4-treated rats at 75 or 375 mg/kg resulted in 61.2-76.2% decrease in alanine aminotransferase (ALT and 46.9-60.8% decrease in aspartate aminotransferase (AST, respectively compared with the CCl4 control group. Silymarin treatment resulted in 34.6 and 30% decrease in ALT and AST, while DDB (75 mg/kg combined with silymarin (22 mg/kg resulted in 58.2 and 31% decrease in ALT and AST, respectively. Serum creatinine increased by 50% by DDB at 375 mg/kg. After treatment with DDB at 75 or 375 mg/kg or DDB combined with silymarin, the development of liver necrosis and fibrosis caused by CCl4 was markedly reduced, while after DDB combined with silymarin no DNA aneuploid cells could be observed. The decrease in glycogen and protein contents in hepatocytes caused by CCl4 was markedly prevented by co-treatment with DDB at 75 or 375 mg/kg or DDB combined with silymarin. It is concluded that in the model of hepatic injury caused by chronic administration of CCl4 in rats, the synthetic compound DDB, limits hepatocellular injury and exerts antifibrotic effect. Better improvement in protein, DNA, mucopolysaccharide content was seen after both DDB and silymarin compared to DDB alone. It is suggested, therefore, that DDB alone or in combination with silymarin might prove of benefit in the therapy of chronic liver disease. Monitoring of kidney functions in patients taking DDB is warranted.

  17. Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in CCl4-induced acute hepatic injury.

    Directory of Open Access Journals (Sweden)

    Atsushi Sato

    Full Text Available We previously reported that F4/80(+ Kupffer cells are subclassified into CD68(+ Kupffer cells with phagocytic and ROS producing capacity, and CD11b(+ Kupffer cells with cytokine-producing capacity. Carbon tetrachloride (CCl4-induced hepatic injury is a well-known chemical-induced hepatocyte injury. In the present study, we investigated the immunological role of Kupffer cells/macrophages in CCl4-induced hepatitis in mice. The immunohistochemical analysis of the liver and the flow cytometry of the liver mononuclear cells showed that clodronate liposome (c-lipo treatment greatly decreased the spindle-shaped F4/80(+ or CD68(+ cells, while the oval-shaped F4/80+ CD11b(+ cells increased. Notably, severe hepatic injury induced by CCl4 was further aggravated by c-lipo-pretreatment. The population of CD11b(+ Kupffer cells/macrophages dramatically increased 24 hour (h after CCl4 administration, especially in c-lipo-pretreated mice. The CD11b(+ Kupffer cells expressed intracellular TNF and surface Fas-ligand (FasL. Furthermore, anti-TNF Ab pretreatment (which decreased the FasL expression of CD11b(+ Kupffer cells, anti-FasL Ab pretreatment or gld/gld mice attenuated the liver injury induced by CCl4. CD1d-/- mouse and cell depletion experiments showed that NKT cells and NK cells were not involved in the hepatic injury. The adoptive transfer and cytotoxic assay against primary cultured hepatocytes confirmed the role of CD11b(+ Kupffer cells in CCl4-induced hepatitis. Interestingly, the serum MCP-1 level rapidly increased and peaked at six h after c-lipo pretreatment, suggesting that the MCP-1 produced by c-lipo-phagocytized CD68(+ Kupffer cells may recruit CD11b(+ macrophages from the periphery and bone marrow. The CD11b(+ Kupffer cells producing TNF and FasL thus play a pivotal role in CCl4-induced acute hepatic injury.

  18. [Pharmacokinetics of lidocaine and its metabolites in dog. Comparison between normal and CCl4-induced hepatic lesion].

    Science.gov (United States)

    Yamane, J

    1989-09-01

    Pharmacokinetic analysis of lidocaine (Lid) and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), was performed in a dog bearing carbon tetrachloride (CCl4, 0.75 ml/kg ip)-induced acute hepatitis. Following pentobarbital sodium (25 mg/kg iv) anesthesia, lidocaine hydrochloride (2.5 mg/kg iv) was given and arterial blood was drawn 2, 5, 10, 15, 30, 45, 60, 90, and 120 min after administration. Lid and its metabolites in plasma were extracted with chloroform-hexane-isopropanol (60 : 30 : 10), and organic layer was dried down at 50 degrees C under N2. The residue was dissolved in 50mM phosphoric acid and subjected to HPLC analysis. 4-compartment model was introduced to analyze pharmacokinetic parameters, and which gave the most reasonable fit with actual results. Control experiment was carried out using identical dog with acute hepatitis. The following results were given: 1) Elimination of Lid was slightly depressed, but T1/2 was not altered. Plasma level of Lid was kept higher. 2) As for MEGX, the formation was depressed, and upto 23 min after Lid administration, MEGX concentration in the dog with acute hepatitis was lower than that of control, but after 23 min it was vice versa. 3) As for GX, the formation was depressed, but the elimination was not affected. In the dog with CCl4-induced hepatitis, metabolism of Lid was suppressed, and which resulted in maintaining a relatively higher levels of Lid and MEGX concentration in plasma. These results suggested that care should be taken to avoid acute poisoning with Lid especially in patients with acute hepatitis. PMID:2489793

  19. Rotational Spectroscopy of CF_2ClCCl_3 and Analysis of Hyperfine Structure from Four Quadrupolar Nuclei

    Science.gov (United States)

    Kisiel, Zbigniew; Bialkowska-Jaworska, Ewa; Uriarte, Iciar; Basterretxea, Francisco J.; Cocinero, Emilio J.

    2016-06-01

    CF_2ClCCl_3 has recently been identified among several new ozone- depleting substances in the atmosphere. There are no literature reports concerning rotational spectroscopy of this molecule, although we were recently able to report its first chirped pulse, supersonic expansion spectrum. CF_2ClCCl_3 has a rather small dipole moment so that the spectrum is weak and each transition displays very complex nuclear quadrupole hyperfine structure resulting from the presence of four chlorine nuclei. We have presently been able to carry out a complete analysis of the hyperfine structure by combining the information from chirped pulse spectra with dedicated higher resolution measurements made with a cavity supersonic expansion instrument. The hyperfine analysis was carried out with Pickett's SPFIT/SPCAT package and the sizes of Hamiltonian matrices are sufficiently large to require the use of 64-bit compilation of these programs (made available for both Windows and Linux systems on the PROSPE website). The resulting fit is to within experimental accuracy and is supported by ab initio calculations. The precise values of off-diagonal hyperfine constants for all nuclei lead to useful angular information that is complementary to direct structural information from moments of inertia. J.C.Laube, M.J.Newland, C.Hogan, et al., Nature Geoscience 7, 266 (2014). Z.Kisiel, E.Białkowska-Jaworska, L.Pszczółkowski, I.Uriarte, P.Ejica, F.J.Basterretxea, E.J.Cocinero, 70th ISMS, Champaign-Urbana, Illinois, RF-11 (2015). Z.Kisiel, E.Białkowska-Jaworska, L.Pszczółkowski, J.Chem.Phys. 109, 10263 (1998).

  20. Human papillomavirus type 8 interferes with a novel C/EBPβ-mediated mechanism of keratinocyte CCL20 chemokine expression and Langerhans cell migration.

    Directory of Open Access Journals (Sweden)

    Tanya Sperling

    Full Text Available Infection with genus beta human papillomaviruses (HPV is implicated in the development of non-melanoma skin cancer. This was first evidenced for HPV5 and 8 in patients with epidermodysplasia verruciformis (EV, a genetic skin disease. So far, it has been unknown how these viruses overcome cutaneous immune control allowing their persistence in lesional epidermis of these patients. Here we demonstrate that Langerhans cells, essential for skin immunosurveillance, are strongly reduced in HPV8-positive lesional epidermis from EV patients. Interestingly, the same lesions were largely devoid of the important Langerhans cells chemoattractant protein CCL20. Applying bioinformatic tools, chromatin immunoprecipitation assays and functional studies we identified the differentiation-associated transcription factor CCAAT/enhancer binding protein β (C/EBPβ as a critical regulator of CCL20 gene expression in normal human keratinocytes. The physiological relevance of this finding is supported by our in vivo studies showing that the expression patterns of CCL20 and nuclear C/EBPβ converge spatially in the most differentiated layers of human epidermis. Our analyses further identified C/EBPβ as a novel target of the HPV8 E7 oncoprotein, which co-localizes with C/EBPβ in the nucleus, co-precipitates with it and interferes with its binding to the CCL20 promoter in vivo. As a consequence, the HPV8 E7 but not E6 oncoprotein suppressed C/EBPβ-inducible and constitutive CCL20 gene expression as well as Langerhans cell migration. In conclusion, our study unraveled a novel molecular mechanism central to cutaneous host defense. Interference of the HPV8 E7 oncoprotein with this regulatory pathway allows the virus to disrupt the immune barrier, a major prerequisite for its epithelial persistence and procarcinogenic activity.

  1. HIV-1 efficient entry in inner foreskin is mediated by elevated CCL5/RANTES that recruits T cells and fuels conjugate formation with Langerhans cells.

    Directory of Open Access Journals (Sweden)

    Zhicheng Zhou

    2011-06-01

    Full Text Available Male circumcision reduces acquisition of HIV-1 by 60%. Hence, the foreskin is an HIV-1 entry portal during sexual transmission. We recently reported that efficient HIV-1 transmission occurs following 1 h of polarized exposure of the inner, but not outer, foreskin to HIV-1-infected cells, but not to cell-free virus. At this early time point, Langerhans cells (LCs and T-cells within the inner foreskin epidermis are the first cells targeted by the virus. To gain in-depth insight into the molecular mechanisms governing inner foreskin HIV-1 entry, foreskin explants were inoculated with HIV-1-infeceted cells for 4 h. The chemokine/cytokine milieu secreted by the foreskin tissue, and resulting modifications in density and spatial distribution of T-cells and LCs, were then investigated. Our studies show that in the inner foreskin, inoculation with HIV-1-infected cells induces increased CCL5/RANTES (1.63-fold and decreased CCL20/MIP-3-alpha (0.62-fold secretion. Elevated CCL5/RANTES mediates recruitment of T-cells from the dermis into the epidermis, which is blocked by a neutralizing CCL5/RANTES Ab. In parallel, HIV-1-infected cells mediate a bi-phasic modification in the spatial distribution of epidermal LCs: attraction to the apical surface at 1 h, followed by migration back towards the basement membrane later on at 4 h, in correlation with reduced CCL20/MIP-3-alpha at this time point. T-cell recruitment fuels the continuous formation of LC-T-cell conjugates, permitting the transfer of HIV-1 captured by LCs. Together, these results reveal that HIV-1 induces a dynamic process of immune cells relocation in the inner foreskin that is associated with specific chemokines secretion, which favors efficient HIV-1 entry at this site.

  2. CCL2-2518 A/G and CCR2 190 A/G do not influence the outcome of hepatitis C virus infection in the Spanish population

    Institute of Scientific and Technical Information of China (English)

    MA Montes-Cano; JR García-Lozano; J Aguilar-Reina; M Romero-Gómez; N Barroso; A Nú(n)ez-Roldán; MF González-Escribano

    2007-01-01

    AIM: To assess whether CCL2 or interactions between this chemokine and its receptor (CCR2) are associated with outcomes of chronic hepatitis C and with responses to antiviral therapy.METHODS: Two hundred and eighty-four patients with chronic hepatitis C and 193 non-infected matched controls were included in this study. Patients were categorized according to their Scheuer score of hepatic fibrosis as F0-F2 (n = 202) or F3-F4 (n = 82) and according to their response to anti-Hepatitis C virus (HCV) therapy as sustained response (SR, n = 101) or non-sustained response (NSR, n = 98). Genotyping of the -2518 (A/G) CCL2 was performed using PCR-RFLP,genotyping of the 190 (A/G) CCR2 using a PCR-ARMS system, and genotyping of the rs3138042 (G/A) CCR2 using Taqman probes.RESULTS: Univariate analyses identified 4 parameters (infection duration time, viral genotype, gender and AST levels) that tended to influence fibrosis and 7 parameters (CCL2G, CCL2ACCR2A, viremia levels, fibrosis stage, viral genotype, infection duration time and AST levels) that significantly influenced or tended to influence response to treatment. Multivariate analysis identified gender and AST levels as parameters that independently influenced fibrosis stage and viral genotype and infection duration time were the two parameters that independently influenced response to treatment.CONCLUSION: Our results indicate that the mutations studied in the gene pair CCL2/CCR2 do not play a major role in the outcome and response to treatment for HCV infection in the Spanish population.

  3. FT-IR study on interactions between medroxyprogesterone acetate and solvent in CHCl3/cyclo-C6H12 and CCl4/cyclo-C6H12 binary solvent systems

    Science.gov (United States)

    Shi, Jie-hua; Fan, Chun-hui

    2012-09-01

    The intermolecular interactions between medroxyprogesterone acetate (MPA) and CHCl3 and CCl4 solvent in CHCl3/cyclo-C6H12 and CCl4/cyclo-C6H12 binary solvent systems have been studied by Fourier transform infrared spectroscopy (FT-IR). The experimental results showed that there are hydrogen bonding interactions between oxygen atoms of all carbonyl groups in MPA and hydrogen atom of CHCl3 so as to form 1:3 complex of MPA with CHCl3 and produce three new absorption bands at 1728.9-1736.1, 1712.7-1717.4 and 1661.9-1673.8 cm-1, respectively. And, 1:1 complex of MPA with CCl4 is formed in CCl4/cyclo-C6H12 binary solvent as a result of hydrogen bonding interaction between C3 carbonyl group and empty d-orbital in chlorine atom of CCl4 leading to producing new absorption band at 1673.2-1674.2 cm-1. However, all free carbonyl and associated carbonyl stretching vibrations of MPA in CHCl3/cyclo-C6H12 and CCl4/cyclo-C6H12 binary solvent systems shift to lower wavenumbers with the increasing of volume fraction of CHCl3 and CCl4 in binary solvent systems owing to the dipole-dipole interaction and the dipole-induced dipole interaction between MPA and solvents.

  4. Saxton Transportation Operations Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Saxton Transportation Operations Laboratory (Saxton Laboratory) is a state-of-the-art facility for conducting transportation operations research. The laboratory...

  5. Validation of ACE-FTS v2.2 measurements of HCl, HF, CCl3F and CCl2F2 using space-, balloon- and ground-based instrument observations

    Directory of Open Access Journals (Sweden)

    C. Servais

    2008-10-01

    Full Text Available Hydrogen chloride (HCl and hydrogen fluoride (HF are respectively the main chlorine and fluorine reservoirs in the Earth's stratosphere. Their buildup resulted from the intensive use of man-made halogenated source gases, in particular CFC-11 (CCl3F and CFC-12 (CCl2F2, during the second half of the 20th century. It is important to continue monitoring the evolution of these source gases and reservoirs, in support of the Montreal Protocol and also indirectly of the Kyoto Protocol. The Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS is a space-based instrument that has been performing regular solar occultation measurements of over 30 atmospheric gases since early 2004. In this validation paper, the HCl, HF, CFC-11 and CFC-12 version 2.2 profile data products retrieved from ACE-FTS measurements are evaluated. Volume mixing ratio profiles have been compared to observations made from space by MLS and HALOE, and from stratospheric balloons by SPIRALE, FIRS-2 and Mark-IV. Partial columns derived from the ACE-FTS data were also compared to column measurements from ground-based Fourier transform instruments operated at 12 sites. ACE-FTS data recorded from March 2004 to August 2007 have been used for the comparisons. These data are representative of a variety of atmospheric and chemical situations, with sounded air masses extending from the winter vortex to summer sub-tropical conditions. Typically, the ACE-FTS products are available in the 10–50 km altitude range for HCl and HF, and in the 7–20 and 7–25 km ranges for CFC-11 and -12, respectively. For both reservoirs, comparison results indicate an agreement generally better than 5–10% above 20 km altitude, when accounting for the known offset affecting HALOE measurements of HCl and HF. Larger positive differences are however found for comparisons with single profiles from FIRS-2 and SPIRALE. For CFCs, the few coincident measurements available suggest that the differences

  6. Validation of ACE-FTS v2.2 measurements of HCl, HF, CCl3F and CCl2F2 using space-, balloon- and ground-based instrument observations

    Directory of Open Access Journals (Sweden)

    C. Tétard

    2008-02-01

    Full Text Available Hydrogen chloride (HCl and hydrogen fluoride (HF are respectively the main chlorine and fluorine reservoirs in the Earth's stratosphere. Their buildup resulted from the intensive use of man-made halogenated source gases, in particular CFC-11 (CCl3F and CFC-12 (CCl2F2, during the second half of the 20th century. It is important to continue monitoring the evolution of these source gases and reservoirs, in support of the Montreal Protocol and also indirectly of the Kyoto Protocol. The Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS is a space-based instrument that has been performing regular solar occultation measurements of over 30 atmospheric gases since early 2004. In this validation paper, the HCl, HF, CFC-11 and CFC-12 version 2.2 profile data products retrieved from ACE-FTS measurements are evaluated. Volume mixing ratio profiles have been compared to observations made from space by MLS and HALOE, and from stratospheric balloons by SPIRALE, FIRS-2 and Mark-IV. Partial columns derived from the ACE-FTS data were also compared to column measurements from ground-based Fourier transform instruments operated at 12 sites. ACE-FTS data recorded from March 2004 to August 2007 have been used for the comparisons. These data are representative of a variety of atmospheric and chemical situations, with sounded air masses extending from the winter vortex to summer sub-tropical conditions. Typically, the ACE-FTS products are available in the 10–50 km altitude range for HCl and HF, and in the 7–20 and 7–25 km ranges for CFC-11 and CFC-12, respectively. For both reservoirs, comparison results indicate an agreement generally better than 5–10%, when accounting for the known offset affecting HALOE measurements of HCl and HF. Larger positive differences are however found for comparisons with single profiles from FIRS-2 and SPIRALE. For CFCs, the few coincident measurements available suggest that the differences probably remain

  7. Lunar laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Keaton, P.W.; Duke, M.B.

    1986-01-01

    An international research laboratory can be established on the Moon in the early years of the 21st Century. It can be built using the transportation system now envisioned by NASA, which includes a space station for Earth orbital logistics and orbital transfer vehicles for Earth-Moon transportation. A scientific laboratory on the Moon would permit extended surface and subsurface geological exploration; long-duration experiments defining the lunar environment and its modification by surface activity; new classes of observations in astronomy; space plasma and fundamental physics experiments; and lunar resource development. The discovery of a lunar source for propellants may reduce the cost of constructing large permanent facilities in space and enhance other space programs such as Mars exploration. 29 refs.

  8. Virtual Laboratories

    CERN Document Server

    Hut, P

    2006-01-01

    At the frontier of most areas in science, computer simulations play a central role. The traditional division of natural science into experimental and theoretical investigations is now completely outdated. Instead, theory, simulation, and experimentation form three equally essential aspects, each with its own unique flavor and challenges. Yet, education in computational science is still lagging far behind, and the number of text books in this area is minuscule compared to the many text books on theoretical and experimental science. As a result, many researchers still carry out simulations in a haphazard way, without properly setting up the computational equivalent of a well equipped laboratory. The art of creating such a virtual laboratory, while providing proper extensibility and documentation, is still in its infancy. A new approach is described here, Open Knowledge, as an extension of the notion of Open Source software. Besides open source code, manuals, and primers, an open knowledge project provides simul...

  9. Laboratory investigations

    International Nuclear Information System (INIS)

    Our task is to design mined-repository systems that will adequately secure high-level nuclear waste for at least 10,000 yr and that will be mechanically stable for 50 to 100-yr periods of retrievability during which mistakes could be corrected and a valuable source of energy could be reclaimed, should national policy on the reprocessing of spent fuel ever change. The only credible path for the escape of radionuclides from the repository to the biosphere is through ground-water, and in hard rock, bulk permeability is largely governed by natural and artificial fracture systems. Catastrophic failure of an excavation in hard rock is likely to occur at the weakest links - the discontinuities in the rock mass that is perturbed first by mining and then by radiogenic heating. The laboratory can contribute precise measurements of the pertinent thermomechanical, hydrological and chemical properties and improve our understanding of the fundamental processes through careful experiments under well controlled conditions that simulate the prototype environment. Thus laboratory investigations are necessary, but they are not sufficient, for conventional sample sizes are small relative to natural defects like joints - i.e., the rock mass is not a continuum - and test durations are short compared to those that predictive modeling must take into account. Laboratory investigators can contribute substantially more useful data if they are provided facilities for testing large specimens(say one cubic meter) and for creep testing of all candidate host rocks. Even so, extrapolations of laboratory data to the field in neither space nor time are valid without the firm theoretical foundations yet to be built. Meanwhile in-situ measurements of structure-sensitive physical properties and access to direct observations of rock-mass character will be absolutely necessary

  10. Culham Laboratory

    International Nuclear Information System (INIS)

    The report contains summaries of work carried out under the following headings: fusion research experiments; U.K. contribution to the JET project; supporting studies; theoretical plasma physics, computational physics and computing; fusion reactor studies; engineering and technology; contract research; external relations; staff, finance and services. Appendices cover main characteristics of Culham fusion experiments, staff, extra-mural projects supported by Culham Laboratory, and a list of papers written by Culham staff. (U.K.)

  11. S-wave threshold in electron attachment - observations and cross sections in CCl4 and SF6 at ultralow electron energies

    International Nuclear Information System (INIS)

    The threshold photoionization method was used to study low-energy electron attachment phenomena in and cross sections of CCl4 and SF6 compounds, which have applications in the design of gaseous dielectrics and diffuse discharge opening switches. Measurements were made at electron energies from below threshold to 140 meV at resolutions of 6 and 8 meV. A narrow resolution-limited structure was observed in electron attachment to CCl4 and SF6 at electron energies below 10 meV, which is attributed to the divergence of the attachment cross section in the limit epsilon, l approaches zero. The results are compared with experimental collisional-ionization results, electron-swarm unfolded cross sections, and earlier threshold photoionization data. 34 refs

  12. Effect of 3 amino 1,2,4 triazole administration on the early CCl4-induced ultrastructural alterations in rat liver.

    OpenAIRE

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; de Fenos, O. M.; Castro, J.A.

    1982-01-01

    CCl4 administration to rats caused at 3 and 6 h intense effects on the liver-cell endoplasmic reticulum such as dilatation, disorganization, detachment of ribosomes, development of extensive areas of smooth component (SER) and formation of myelin figures. 3 Amino 1,2,4 triazole administration (AT) at 3 and 6 h led to the formation of round small vesicles from the rough endoplasmic reticulum (RER), detachment of ribosomes, appearance of extensive areas of SER, appearance of elongated and disto...

  13. Re-evaluation of the lifetimes of the major CFCs and CH3CCl3 using atmospheric trends

    OpenAIRE

    J. W. Elkins; Krummel, P.B.; Mondeel, D. J.; D. Nance; G. S. Dutton; Hall, B D; P. G. Simmonds; Young, D.; Weiss, R. F.; P. K. Salameh; Mühle, J.; C. M. Harth; McCulloch, A; Montzka, S. A.; S. O'Doherty

    2012-01-01

    Since the Montreal Protocol on substances that deplete the ozone layer and its amendments came into effect, growth rates of the major ozone depleting substances (ODS), particularly CFC-11, -12 and -113 and CH3CCl3, have declined markedly, paving the way for global stratospheric ozone recovery. Emissions have now fallen to relatively low levels, therefore the rate at which this recovery occurs will depend largely on the atmospheric lifetime of these compounds. The first ODS measurements beg...

  14. Re-evaluation of the lifetimes of the major CFCs and CH[subscript 3]CCl[subscript 3] using atmospheric trends

    OpenAIRE

    Rigby, M.; R. G. Prinn; S. O'Doherty; Montzka, S. A.; McCulloch, A; C. M. Harth; Mühle, J.; P. K. Salameh; Weiss, R. F.; Young, D.; P. G. Simmonds; Hall, B D; G. S. Dutton; D. Nance; Mondeel, D. J.

    2013-01-01

    Since the Montreal Protocol on Substances that Deplete the Ozone Layer and its amendments came into effect, growth rates of the major ozone depleting substances (ODS), particularly CFC-11, -12 and -113 and CH3CCl3, have declined markedly, paving the way for global stratospheric ozone recovery. Emissions have now fallen to relatively low levels, therefore the rate at which this recovery occurs will depend largely on the atmospheric lifetime of these compounds. The first ODS measurements began ...

  15. Astrocyte elevated gene-1 regulates CCL3/CCR5-induced epithelial-to-mesenchymal transition via Erk1/2 and Akt signaling in cardiac myxoma.

    Science.gov (United States)

    Shi, Ping; Fang, Changcun; Pang, Xinyan

    2015-09-01

    In recent years, astrocyte elevated gene-1 (AEG-1) has been reported as a key mediator that is involved in the epithelial-to-mesenchymal transition (EMT) process. However, the mechanisms underlying CCL3/CCR5-AEG-1 pathway-mediated EMT in cardiac myxoma (CM) has not been well featured till now. We used immnohistochemistry and immunoblotting to assess the expression of CCR5 and AEG-1 in 30 cases of CM tissues and cells. Subsequently, cultured CM cells were treated with si-AEG-1 or si-CCR5 and then subjected to in vitro assays. We observed that CCR5 and AEG-1 proteins were highly expressed in CM tissues (73.3 and 76.7%, respectively) and closely correlated with tumor size (>5 cm). Importantly, we validated the expression of AEG-1, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 increased in the CM cell with CCL3 treatment in a time- and concentration-dependent manner. When CM cells were treated with si-CCR5, the expression of AEG-1, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 was downregulated. In addition, when CM cells were treated with si-AEG-1, the expression of p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 was also downregulated. Using the cell cycle and proliferation assay, the knockdown of AEG-1 inhibited the entry of G1 into S phase and the proliferation capacity of CM cells. In conclusion, AEG-1 mediates CCL3/CCR5-induced EMT development via both Erk1/2 and Akt signaling pathway in CM patients, which indicates CCL3/CCR5-AEG-1-EMT pathway could be suggested as a useful target to affect the progression of CM.

  16. Impact of Increased Astrocyte Expression of IL-6, CCL2 or CXCL10 in Transgenic Mice on Hippocampal Synaptic Function

    Science.gov (United States)

    Gruol, Donna L.

    2016-01-01

    An important aspect of CNS disease and injury is the elevated expression of neuroimmune factors. These factors are thought to contribute to processes ranging from recovery and repair to pathology. The complexity of the CNS and the multitude of neuroimmune factors that are expressed in the CNS during disease and injury is a challenge to an understanding of the consequences of the elevated expression relative to CNS function. One approach to address this issue is the use of transgenic mice that express elevated levels of a specific neuroimmune factor in the CNS by a cell type that normally produces it. This approach can provide basic information about the actions of specific neuroimmune factors and can contribute to an understanding of more complex conditions when multiple neuroimmune factors are expressed. This review summarizes studies using transgenic mice that express elevated levels of IL-6, CCL2 or CXCL10 through increased astrocyte expression. The studies focus on the effects of these neuroimmune factors on synaptic function at the Schaffer collateral to CA1 pyramidal neuron synapse of the hippocampus, a brain region that plays a key role in cognitive function. PMID:27322336

  17. Anti-apoptotic effect of San Huang Shel Shin Tang cyclodextrin complex (SHSSTc) on CCl4 -induced hepatotoxicity in rats.

    Science.gov (United States)

    Yang, Cheng-Hsun; Ting, Wei-Jen; Shen, Chia-Yao; Hsu, Hsi-Hsien; Lin, Yueh-Min; Kuo, Chia-Hua; Tsai, Fuu-Jen; Tsai, Chang-Hai; Tsai, Yuhsin; Huang, Chih-Yang

    2016-06-01

    The metabolic loading is heavier in liver especially when injured or inflammation. San Huang Shel Shin Tang (SHSST) was an old traditional herbal decoction, which composed with Rheum officinale Baill, Scutellaria baicalnsis Geprgi and Coptis chinensis Franch (1:1:2 in weight), can provide a liver protection effects. We used a beta-cyclodextrin (β-CD) drug modification method in reduce of the necessary dose of the SHSST. As the results, the FAS-FADD expressions leaded apoptosis in CCl4 intraperitoneal (IP) injection induced acute liver injury in rats. Silymarin, baicalein, SHSST, and SHSST β-CD complex (SHSSTc) pretreatments protected liver through the decreasing of the expressions of FAS-FADD and downstream caspase-3 and caspase-8. Particularly, SHSSTc (30 mg/kg day) treatment enhanced cell survival pathway activation through the PI3K, Akt and Bad phosphorylation. Compared with SHSST as well as silymarin and baicalein, SHSSTc provided a magnificent liver protection effect, especially in survival pathway activation/TUNEL-apoptotic cell reduction/serum cholesterol level suppression. All these data suggested that β-CD complex modified the SHSST and promoted the bioavailability and liver protection effects. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 663-670, 2016.

  18. Recovery of the Cell Cycle Inhibition in CCl4-Induced Cirrhosis by the Adenosine Derivative IFC-305

    Directory of Open Access Journals (Sweden)

    Victoria Chagoya de Sánchez

    2012-01-01

    Full Text Available Introduction. Cirrhosis is a chronic degenerative illness characterized by changes in normal liver architecture, failure of hepatic function, and impairment of proliferative activity. The aim of this study is to know how IFC-305 compound induces proliferation of the liver during reversion of cirrhosis. Methods. Once cirrhosis has been installed by CCl4 treatment for 10 weeks in male Wistar rats, they were divided into four groups: two received saline and two received the compound; all were euthanized at 5 and 10 weeks of treatment. Liver homogenate, mitochondria, and nucleus were used to measure cyclins, CDKs, and cell cycle regulatory proteins PCNA, pRb, p53, E2F, p21, p27, HGF, liver ATP, and mitochondrial function. Results. Diminution and small changes were observed in the studied proteins in the cirrhotic animals without treatment. The IFC-305-treated rats showed a clear increase in most of the proteins studied mainly in PCNA and CDK6, and a marked increased in ATP and mitochondrial function. Discussion/Conclusion. IFC-305 induces a recovery of the cell cycle inhibition promoting recovery of DNA damage through the action of PCNA and p53. The increase in energy and preservation of mitochondrial function contribute to recovering the proliferative function.

  19. Hepatoprotective effect ofSolanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals

    Institute of Scientific and Technical Information of China (English)

    Ramesh K Gupta; Talib Hussain; G Panigrahi; Avik Das; Gireesh Narayan Singh; K Sweety; Md Faiyazuddin; Chandana Venkateswara Rao

    2011-01-01

    Objective:To investigate the hepatoprotective potential ofSolanum xanthocarpum (Solanaceae) (S. xanthocarpum) in experimental rats to validate its traditional claim.Methods: 50%ethanolic fruit extract ofS. xanthocarpum (SXE, 100, 200or400 mg/kg body weight) was administered daily for14days in experimental animals. Liver injury was induced chemically, byCCl4administration (1 mL/kg i.p.).The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase(ALT), Serum alkaline phosphatise (SALP) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were screened along with histopathological studies.Results: Obtained results demonstrated that the treatment with SXE significantly (P<0.05- <0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore,SXE significantly (up toP<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed thatSXE attenuated the hepatocellular necrosis and led to reduction of inflammatory cells inflltration. Conclusions: The results of this study strongly indicate the protective effect ofSXE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use.

  20. Effectiveness of xenotransplantation of human fetal hepatocytes in spleen of rats with acute liver failure induced by CCL4

    Directory of Open Access Journals (Sweden)

    Abdukhakim Khadjibaev

    2013-04-01

    Full Text Available Human’s fetal hepatocytes (HFH were intrasplenic transplanted white non-pedigree rats with acute liver failure (ALF challenged by single per oral administration of hepatotropic toxin diluted in oil ССl4 at a dose 10 ml/kg (volumetric correlation 1:1 (10 mL/kg body weight as a 1:1 mixture of CCl4 and mineral oil. Transplantation had positive effect on all biochemical blood parameters of the studying animals. Morphologic study showed that reparative-restorative processes were arising in hepatic parenchyma after administration of HFH into splenic pulp of rats with model of ALF on days 14-21. Substantial and main factor in restoration of parenchyma was restoration of micro topographic interrelations in acinus as well as polyploidy of hepatic cells expressed in increase of hepatocytes’ nuclei sizes and hypertrophy of cells themselves. It is an indirect confirmation of engraftment of HFH in liver of rats with model of ALF.

  1. HIV-1 Tat-mediated induction of CCL5 in astrocytes involves NF-κB, AP-1, C/EBPα and C/EBPγ transcription factors and JAK, PI3K/Akt and p38 MAPK signaling pathways.

    Directory of Open Access Journals (Sweden)

    Anantha R Nookala

    Full Text Available The incidence of HIV-associated neurological disorders (HAND has increased during recent years even though the highly active antiretroviral therapy (HAART has significantly curtailed the virus replication and increased the life expectancy among HIV-1 infected individuals. These neurological deficits have been attributed to HIV proteins including HIV-1 Tat. HIV-1 Tat is known to up-regulate CCL5 expression in mouse astrocytes, but the mechanism of up-regulation is not known. The present study was undertaken with the objective of determining the mechanism(s underlying HIV-1 Tat-mediated expression of CCL5 in astrocytes. SVGA astrocytes were transiently transfected with a plasmid encoding Tat, and expression of CCL5 was studied at the mRNA and protein levels using real time RT-PCR and multiplex cytokine bead array, respectively. HIV-1 Tat showed a time-dependent increase in the CCL5 expression with peak mRNA and protein levels, observed at 1 h and 48 h post-transfection, respectively. In order to explore the mechanism(s, pharmacological inhibitors and siRNA against different pathway(s were used. Pre-treatment with SC514 (NF-κB inhibitor, LY294002 (PI3K inhibitor, AG490 (JAK2 inhibitor and Janex-1 (JAK3 inhibitor showed partial reduction of the Tat-mediated induction of CCL5 suggesting involvement of JAK, PI3K/Akt and NF-κB in CCL5 expression. These results were further confirmed by knockdown of the respective genes using siRNA. Furthermore, p38 MAPK was found to be involved since the knockdown of p38δ but not other isoforms showed partial reduction in CCL5 induction. This was further confirmed at transcriptional level that AP-1, C/EBPα and C/EBPγ were involved in CCL5 up-regulation.

  2. Effect of chain length on aggregation of n-alkanes in CCl3F matrices at 77 K. Further ESR evidence for the occurrence of hydrogen and/or proton transfer between higher alkanes and their cations

    International Nuclear Information System (INIS)

    After γ-irradiation of hexane and decane at low concentration in CCl3F at 77 K only the ESR spectrum of the corresponding radical cations is observed. At higher concentrations (from about 3 mol% hexane and 0.5 mol% decane), the spectra of alkyl radicals also appear. The signal intensity and relative contribution of these alkyl radicals to the observed ESR spectra increases with increasing alkane solute concentration. In contrast, alkane radical cations but no alkyl radicals are observed after irradiation of hexane and decane in CCl3CF3 and other matrices at concentrations where alkyl radicals are already quite prominent in CCl3F. This contrast is especially pronounced in the case of decane, the signal intensity and relative contribution of alkyl radicals in the ESR spectrum of irradiated CCl3F-decane systems being much higher than in irradiated CCl3F-hexane systems. Most of the alkane radical cations observed possess the extended structure, resulting in a triplet with substructure for hexane and a broad singlet for decane, but different conformers are also observed, viz. for hexane in CCl3CF3 and for decane in CCl3F. The results provide conclusive evidence for the occurrence of hydrogen and/or proton transfer between C6 (only weakly) and C10 (very pronounced) n-alkanes and their cations. They show further that in CCl3F at 77 K alkanes are present as small aggregates to which hole transfer still occurs efficiently and, in conjunction with other data, indicate that the extent of such aggregation increases with increasing chain length of the alkane solute. (Author)

  3. The Macrophage Inflammatory Proteins MIP1α (CCL3 and MIP2α (CXCL2 in Implant-Associated Osteomyelitis: Linking Inflammation to Bone Degradation

    Directory of Open Access Journals (Sweden)

    Ulrike Dapunt

    2014-01-01

    Full Text Available Bacterial infections of bones remain a serious complication of endoprosthetic surgery. These infections are difficult to treat, because many bacterial species form biofilms on implants, which are relatively resistant towards antibiotics. Bacterial biofilms elicit a progressive local inflammatory response, resulting in tissue damage and bone degradation. In the majority of patients, replacement of the prosthesis is required. To address the question of how the local inflammatory response is linked to bone degradation, tissue samples were taken during surgery and gene expression of the macrophage inflammatory proteins MIP1α (CCL3 and MIP2α (CXCL2 was assessed by quantitative RT-PCR. MIPs were expressed predominantly at osteolytic sites, in close correlation with CD14 which was used as marker for monocytes/macrophages. Colocalisation of MIPs with monocytic cells could be confirmed by histology. In vitro experiments revealed that, aside from monocytic cells, also osteoblasts were capable of MIP production when stimulated with bacteria; moreover, CCL3 induced the differentiation of monocytes to osteoclasts. In conclusion, the multifunctional chemokines CCL3 and CXCL2 are produced locally in response to bacterial infection of bones. In addition to their well described chemokine activity, these cytokines can induce generation of bone resorbing osteoclasts, thus providing a link between bacterial infection and osteolysis.

  4. «Evaluation of the anti-icterus effect of crude powdered leaf of Argemone mexicana L. (Papaveraceae against CCl4-induced liver injury in rats».

    Directory of Open Access Journals (Sweden)

    T.S. SOURABIE

    2012-10-01

    Full Text Available Leaves of Argemone mexicana L. (Papaveraceae are used in the folk medicine of Burkina Faso (West Africa to treat a variety of illness. Aqueous decoction of the drug is indicated in the treatment of malaria fever, abdominal pains, and jaundice. A preliminary study led by the authors showed a good anti-icterus (hepatoprotective activity of leaves extracts on intoxicated Wistar rats. The aim of the present investigation was to evaluate the anti-icterus activity of crude leaf powder against CCl4 induced hepatotoxicity in rats. Liver functions were assessed by the activities of liver marker enzymes, ASAT/GOT, ALAT/GPT, ALP, Total Bilirubin (TBIL and Direct Bilirubin (DBIL.A crude powdered leaf suspended in acacia gum solution (2% p/w was administered orally to the animal at doses of 125, 250 and 500 mg/kg attenuated significantly (p<0,05 the elevation of serum enzymes level and bilirubin (total and direct if compared to the CCl4 treated groups. Silymarin (100 mg/kg, p.o., a known antihepatoprotective drug was used as reference. The results showed a dose-dependent anti-hepatotoxic effect against liver injury induced by CCl4 in rats. These findings give an opportunity for a future elaboration of galenic formulation as phytomedicament.

  5. Marsdenia tenacissima extract suppresses A549 cell migration through regulation of CCR5-CCL5 axis, Rho C, and phosphorylated FAK.

    Science.gov (United States)

    Lin, Sen-Sen; Li, Fang-Fang; Sun, Li; Fan, Wei; Gu, Ming; Zhang, Lu-Yong; Qin, Song; Yuan, Sheng-Tao

    2016-03-01

    Marsdenia tenacissima, a traditional Chinese medicine, is long been used to treat various diseases including asthma, cancer, trachitis, tonsillitis, pharyngitis, cystitis, and pneumonia. Although Marsdenia tenacissima has been demonstrated to have strong anti-tumor effects against primary tumors, its effect on cancer metastasis remains to be defined, and the molecular mechanism underlying the anti-metastatic effect is unknown. In the present study, we investigated the effects of XAP (an extract of Marsdenia tenacissima) on A549 lung cancer cell migration and explored the role of CCR5-CCL5 axis in the anti-metastatic effects of XAP. Our resutls showed that XAP inhibited A549 lung cancer cell migration and invasion in a dose-dependent manner. The protein levels of CCR5, but not CCR9 and CXCR4, were decreased by XAP. The secretion of CCL5, the ligand of CCR5, was reduced by XAP. XAP down-regulated Rho C expression and FAK phosphorylation. In conclusion, XAP inhibited A549 cell migration and invasion through down-regulation of CCR5-CCL5 axis, Rho C, and FAK. PMID:27025367

  6. Marsdenia tenacissima extract suppresses A549 cell migration through regulation of CCR5-CCL5 axis, Rho C, and phosphorylated FAK.

    Science.gov (United States)

    Lin, Sen-Sen; Li, Fang-Fang; Sun, Li; Fan, Wei; Gu, Ming; Zhang, Lu-Yong; Qin, Song; Yuan, Sheng-Tao

    2016-03-01

    Marsdenia tenacissima, a traditional Chinese medicine, is long been used to treat various diseases including asthma, cancer, trachitis, tonsillitis, pharyngitis, cystitis, and pneumonia. Although Marsdenia tenacissima has been demonstrated to have strong anti-tumor effects against primary tumors, its effect on cancer metastasis remains to be defined, and the molecular mechanism underlying the anti-metastatic effect is unknown. In the present study, we investigated the effects of XAP (an extract of Marsdenia tenacissima) on A549 lung cancer cell migration and explored the role of CCR5-CCL5 axis in the anti-metastatic effects of XAP. Our resutls showed that XAP inhibited A549 lung cancer cell migration and invasion in a dose-dependent manner. The protein levels of CCR5, but not CCR9 and CXCR4, were decreased by XAP. The secretion of CCL5, the ligand of CCR5, was reduced by XAP. XAP down-regulated Rho C expression and FAK phosphorylation. In conclusion, XAP inhibited A549 cell migration and invasion through down-regulation of CCR5-CCL5 axis, Rho C, and FAK.

  7. Snailase Preparation of Ginsenoside M1 from Protopanaxadiol-Type Ginsenoside and Their Protective Effects Against CCl4-Induced Chronic Hepatotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    Li Chen

    2011-12-01

    Full Text Available To investigate the protective effects of protopanaxadiol-type ginsenoside (PDG and its metabolite ginsenoside M1 (G-M1 on carbon tetrachloride (CCl4-induced chronic liver injury in ICR mice, we carried out conversion of protopanaxadiol-type ginsenosides to ginsenoside M1 using snailase. The optimum time for the conversion was 24 h at a constant pH of 4.5 and an optimum temperature of 50 °C. The transformation products were identified by high-performance liquid chromatography and electrospray ion-mass spectrometry. Subsequently, most of PDG was decomposed and converted into G-M1 by 24 h post-reaction. During the study on hepatoprotective in a mice model of chronic liver injury, PDG or G-M1 supplement significantly ameliorated the CCl4-induced liver lesions, lowered the serum levels of select hepatic enzyme markers (alanine aminotransferase, ALT, and aspartate aminotransferase, AST and malondialdehyde and increased the activity of superoxide dismutase in liver. Histopathology of the liver tissues showed that PDG and G-M1 attenuated the hepatocellular necrosis and led to reduction of inflammatory cell infiltration. Therefore, the results of this study show that PDG and G-M1 can be proposed to protect the liver against CCl4-induced oxidative injury in mice, and the hepatoprotective effect might be attributed to amelioration of oxidative stress.

  8. HIV-1 Nef Induces CCL5 production in astrocytes through p38-MAPK and PI3K/Akt pathway and utilizes NF-kB, CEBP and AP-1 transcription factors

    Science.gov (United States)

    Liu, Xun; Shah, Ankit; Gangwani, Mohitkumar R.; Silverstein, Peter S.; Fu, Mingui; Kumar, Anil

    2014-03-01

    The prevalence of HIV-associated neurocognitive disorders (HAND) remains high in patients infected with HIV-1. The production of pro-inflammatory cytokines by astrocytes/microglia exposed to viral proteins is thought to be one of the mechanisms leading to HIV-1- mediated neurotoxicity. In the present study we examined the effects of Nef on CCL5 induction in astrocytes. The results demonstrate that CCL5 is significantly induced in Nef-transfected SVGA astrocytes. To determine the mechanisms responsible for the increased CCL5 caused by Nef, we employed siRNA and chemical antagonists. Antagonists of NF-κB, PI3K, and p38 significantly reduced the expression levels of CCL5 induced by Nef transfection. Furthermore, specific siRNAs demonstrated that the Akt, p38MAPK, NF-κB, CEBP, and AP-1 pathways play a role in Nef-mediated CCL5 expression. The results demonstrated that the PI3K/Akt and p38 MAPK pathways, along with the transcription factors NF-κB, CEBP, and AP-1, are involved in Nef-induced CCL5 production in astrocytes.

  9. Antioxidative effects of pumpkin seed (Cucurbita pepo) protein isolate in CCl4-induced liver injury in low-protein fed rats.

    Science.gov (United States)

    Nkosi, C Z; Opoku, A R; Terblanche, S E

    2006-11-01

    The effects of pumpkin seed (Cucurbita pepo) protein isolate on the plasma activity levels of catalase (CA), superoxide dismutase (SOD), glutathione peroxidase (GSHpx) and total antioxidant capacity (TAC) as well as glucose-6-phosphatase (G6Pase) in liver homogenates and lipid peroxidation (LPO-malondialdehyde-MDA) levels in liver homogenates and liver microsomal fractions against carbon tetrachloride (CCl(4))-induced acute liver injury in low-protein fed Sprague-Dawley rats (Rattus norvegicus) were investigated. A group of male Sprague-Dawley rats maintained on a low-protein diet for 5 days were divided into three subgroups. Two subgroups were injected with carbon tetrachloride and the other group with an equivalent amount of olive oil. Two hours after CCl(4) intoxication one of the two subgroups was administered with pumpkin seed protein isolate and thereafter switched onto a 20% pumpkin seed protein isolate diet. The other two groups of rats were maintained on the low-protein diet for the duration of the investigation. Groups of rats from the different subgroups were killed at 24, 48 and 72 h after their respective treatments. After 5 days on the low-protein diet the activity levels of all the enzymes as well as antioxidant levels were significantly lower than their counterparts on a normal balanced diet. However, a low-protein diet resulted in significantly increased levels of lipid peroxidation. The CCl(4) intoxicated rats responded in a similar way, regarding all the variables investigated, to their counterparts on a low-protein diet. The administration of pumpkin seed protein isolate after CCl(4) intoxication resulted in significantly increased levels of all the variables investigated, with the exception of the lipid peroxidation levels which were significantly decreased. From the results of the present study it is concluded that pumpkin seed protein isolate administration was effective in alleviating the detrimental effects associated with protein

  10. Physical Sciences Laboratory (PSL)

    Data.gov (United States)

    Federal Laboratory Consortium — PNNL's Physical Sciences Laboratory (PSL) houses 22 research laboratories for conducting a wide-range of research including catalyst formulation, chemical analysis,...

  11. Bio Engineering Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Description/History: Chemistry and biology laboratories The Bio Engineering Laboratory (BeL) is theonly full spectrum biotechnology capability within the Department...

  12. Distributed Energy Technology Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Distributed Energy Technologies Laboratory (DETL) is an extension of the power electronics testing capabilities of the Photovoltaic System Evaluation Laboratory...

  13. FOOTWEAR PERFORMANCE LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory provides biomechanical and physical analyses for both military and commercial footwear. The laboratory contains equipment that is integral to the us...

  14. Theme: Laboratory Facilities Improvement.

    Science.gov (United States)

    Miller, Glen M.; And Others

    1993-01-01

    Includes "Laboratory Facilities Improvement" (Miller); "Remodeling Laboratories for Agriscience Instruction" (Newman, Johnson); "Planning for Change" (Mulcahy); "Laboratory Facilities Improvement for Technology Transfer" (Harper); "Facilities for Agriscience Instruction" (Agnew et al.); "Laboratory Facility Improvement" (Boren, Dwyer); and…

  15. Co-delivery of GPI-anchored CCL28 and influenza HA in chimeric virus-like particles induces cross-protective immunity against H3N2 viruses.

    Science.gov (United States)

    Mohan, Teena; Kim, Jongrok; Berman, Zachary; Wang, Shelly; Compans, Richard W; Wang, Bao-Zhong

    2016-07-10

    Influenza infection typically initiates at respiratory mucosal surfaces. Induction of immune responses at the sites where pathogens initiate replication is crucial for the prevention of infection. We studied the adjuvanticity of GPI-anchored CCL28 co-incorporated with influenza HA-antigens in chimeric virus-like particles (cVLPs), in boosting strong protective immune responses through an intranasal (i.n.) route in mice. We compared the immune responses to that from influenza VLPs without CCL28, or physically mixed with soluble CCL28 at systemic and various mucosal compartments. The cVLPs containing GPI-CCL28 showed in-vitro chemotactic activity towards spleen and lung cells expressing CCR3/CCR10 chemokine receptors. The cVLPs induced antigen specific endpoint titers and avidity indices of IgG in sera and IgA in tracheal, lung, and intestinal secretions, significantly higher (4-6 fold) than other formulations. Significantly higher (3-5 fold) hemagglutination inhibition titers and high serum neutralization against H3N2 viruses were also detected with CCL28-containing VLPs compared to other groups. The CCL28-containing VLPs showed complete and 80% protection, when vaccinated animals were challenged with A/Aichi/2/1968/H3N2 (homologous) and A/Philippines/2/1982/H3N2 (heterologous) viruses, respectively. Thus, GPI-anchored CCL28 in influenza VLPs act as a strong immunostimulator at both systemic and mucosal sites, boosting significant cross-protection in animals against heterologous viruses across a large distance. PMID:27178810

  16. Synchrotron radiation

    International Nuclear Information System (INIS)

    A detailed account of the research work associated with the Synchrotron Radiation Source at Daresbury Laboratory, United Kingdom, in 1984/85, is presented in the Appendix to the Laboratory's Annual Report. (U.K.)

  17. Hepatoprotective and antioxidant activity of methanolic extract of flowers ofNerium oleander against CCl4-induced liver injury in rats

    Institute of Scientific and Technical Information of China (English)

    Kumar Gaurav Singhal; Ghanshyam Das Gupta

    2012-01-01

    Objective:To investigate the antioxidant and hepatoprotective activity of methanolic flower extract ofNerium oleander againstCCl4-induced hepatotoxicity in rats.Methods:In vitro antioxidant activity of methanolic extract of flowers of Nerium oleander(MENO-F) was evaluated by various assays, including reducing power, lipid peroxidation,DPPH,ABTS, superoxide anion, hydroxyl radicals and metal chelation.The hepatoprotective andin vivo antioxidant activity ofMENO-F were evaluated againstCCl4-induced hepatic damage in rats.TheMENO-F at dose of100,200 and400 mg/kg were administered orally once daily for seven days.Serum enzymatic levels of serum glutamate oxaloacetate transaminase(AST), serum glutamate pyruvate transaminase(ALT), serum alkaline phosphatase(ALP) and total bilirubin were estimated along with estimation of superoxide dismutase(SOD) and malondialdehyde(MDA) levels in liver tissues.Further histopathological examination of the liver sections was carried out to support the induction of hepatotoxicity and hepatoprotective efficacy.Results:The extract showed potent activities on reducing power, lipid peroxide,DPPH,ABTS, superoxide anion, hydroxyl radical and metal chelation.The substantially elevated serum enzymatic levels ofAST,ALT,ALP and total bilirubin were found to be restored towards normalization significantly by theMENO-F in a dose dependent manner with maximum hepatoprotection at400 mg/kg dose level.The histopathological observations supported the biochemical evidences of hepatoprotection.Elevated level ofSOD and decreased level ofMDA further strengthen the hepatoprotective observations.Conclusions:The results of the present study strongly reveal thatMENO-F has potent antioxidant activity and hepatoprotective activity againstCCl4-induced hepatic damage in experimental animals.

  18. Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats

    Directory of Open Access Journals (Sweden)

    Wang Yu

    2012-06-01

    Full Text Available Abstract Introduction Adipose derived mesenchymal stem cells (ADMSCs, carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4 in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway. Methods ADMSCs were isolated, cultured and identified. Placebo and ADMSCs were transplanted via portal vein and tail vein respectively into carbon tetrachloride (CCl4-induced liver fibrosis rats. Computed tomography (CT perfusion scan and microvessel counts were performed to measure the alteration of liver microcirculation after therapy. Liver function tests and histological findings were estimated. Results CT perfusion scan shown significant decrease of hepatic arterial perfusion index, significant increased portal vein perfusion, total liver perfusion in rats receiving ADMSCs from portal vein, and Factor VIII (FVIII immunohistochemical staining shown significant decrease of microvessels in rats receiving ADMSCs from portal vein, indicating microcirculation improvement in portal vein group. Vascular endothelial growth Factor (VEGF was significantly up-regulated in fibrosis models, and decreased after ADMSCs intraportal transplantation. A significant improvement of liver functional test and histological findings in portal vein group were observed. No significance was found in rats receiving ADMSCs from tail vein. Conclusions ADMSCs have a therapeutic effect against CCl4-mediated liver fibrosis. ADMSCs may benefit the fibrotic liver through alteration of microcirculation, evidenced by CT perfusion scan and down-regulation of VEGF. Intraportal transplantation is a better pathway than tail vein transplantation.

  19. Chemokine Ligand 5 (CCL5 and chemokine receptor (CCR5 genetic variants and prostate cancer risk among men of African Descent: a case-control study

    Directory of Open Access Journals (Sweden)

    Kidd LaCreis R

    2012-11-01

    Full Text Available Abstract Background Chemokine and chemokine receptors play an essential role in tumorigenesis. Although chemokine-associated single nucleotide polymorphisms (SNPs are associated with various cancers, their impact on prostate cancer (PCA among men of African descent is unknown. Consequently, this study evaluated 43 chemokine-associated SNPs in relation to PCA risk. We hypothesized inheritance of variant chemokine-associated alleles may lead to alterations in PCA susceptibility, presumably due to variations in antitumor immune responses. Methods Sequence variants were evaluated in germ-line DNA samples from 814 African-American and Jamaican men (279 PCA cases and 535 controls using Illumina’s Goldengate genotyping system. Results Inheritance of CCL5 rs2107538 (AA, GA+AA and rs3817655 (AA, AG, AG+AA genotypes were linked with a 34-48% reduction in PCA risk. Additionally, the recessive and dominant models for CCR5 rs1799988 and CCR7 rs3136685 were associated with a 1.52-1.73 fold increase in PCA risk. Upon stratification, only CCL5 rs3817655 and CCR7 rs3136685 remained significant for the Jamaican and U.S. subgroups, respectively. Conclusions In summary, CCL5 (rs2107538, rs3817655 and CCR5 (rs1799988 sequence variants significantly modified PCA susceptibility among men of African descent, even after adjusting for age and multiple comparisons. Our findings are only suggestive and require further evaluation and validation in relation to prostate cancer risk and ultimately disease progression, biochemical/disease recurrence and mortality in larger high-risk subgroups. Such efforts will help to identify genetic markers capable of explaining disproportionately high prostate cancer incidence, mortality, and morbidity rates among men of African descent.

  20. Evaluation of chemopreventive effect ofFumaria indica against N-nitrosodiethylamine and CCl4-induced hepatocellular carcinoma in Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Talib Hussain; Hefazat H Siddiqui; Sheeba Fareed; M Vijayakumar; Chandana V Rao

    2012-01-01

    Objective:To investigation the chemopreventive potential ofFumaria indica (F. indica) extract (FIE) on N-nitrosodiethylamine and CCl4-induced hepatocarcinogenesis in Wistar rats.Methods:The experimental animals were divided into six groups (n=6). Hepatocellular carcinoma was induced by single intraperitoneal injection ofN-nitrosodiethylamine (NDEA) in normal saline at a dose of 200 mg/kg body weight followed by weekly subcutaneous injections of CCl4 (3 mL/kg/week) for 6 weeks, as the promoter of carcinogenic effect. After administration of the carcinogen, 200 and 400 mg/kg of FIE were administered orally once a day throughout the study. At the end of 20 weeks, the body weight, liver weight and relative liver weight were measured. The percentage of nodule incidence and liver cancer markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP),γ-glutamyl transferase (γ-GT), total bilirubin level (TBL), α-feto protein (AFP) and carcinoembryonic antigen were estimated along with histopathological investigation in experimental groups of rats. Results: Obtained results demonstrated that the cotreatment with FIE significantly prevented the decrease of the body weight and also increased in relative liver weight caused by NDEA. The treatment with FIE significantly reduced the nodule incidence and nodule multiplicity in the rats after NDEA administration. The levels of liver cancer markers such as AST, ALT, ALP,γ-glutamyl transferase, TBL, AFP and carcinoembryonic antigen were substantially increased by NDEA treatment. However, FIE treatment significantly reduced the liver injury and restored the entire liver cancer markers. Histological observations of liver tissues too correlated with the biochemical observations.Conclusions: These finding powerfully supports thatF. indica exert chemopreventive effect by suppressing the tumor burden and restoring the activities of hepatic cancer marker enzymes on NDEA and CCl4-induced

  1. 5, 8, 11, 14-eicosatetraynoic acid suppresses CCL2/MCP-1 expression in IFN-γ-stimulated astrocytes by increasing MAPK phosphatase-1 mRNA stability

    Directory of Open Access Journals (Sweden)

    Lee Jee

    2012-02-01

    Full Text Available Abstract Background The peroxisome proliferator-activated receptor (PPAR-α activator, 5,8,11,14-eicosatetraynoic acid (ETYA, is an arachidonic acid analog. It is reported to inhibit up-regulation of pro-inflammatory genes; however, its underlying mechanism of action is largely unknown. In the present study, we focused on the inhibitory action of ETYA on the expression of the chemokine, CCL2/MCP-1, which plays a key role in the initiation and progression of inflammation. Methods To determine the effect of ETYA, primary cultured rat astrocytes and microglia were stimulated with IFN-γ in the presence of ETYA and then, expression of CCL2/MCP-1 and MAPK phosphatase (MKP-1 were determined using RT-PCR and ELISA. MKP-1 mRNA stability was evaluated by treating actinomycin D. The effect of MKP-1 and human antigen R (HuR was analyzed by using specific siRNA transfection system. The localization of HuR was analyzed by immunocytochemistry and subcellular fractionation experiment. Results We found that ETYA suppressed CCL2/MCP-1 transcription and secretion of CCL2/MCP-1 protein through up-regulation of MKP-1mRNA levels, resulting in suppression of c-Jun N-terminal kinase (JNK phosphorylation and activator protein 1 (AP1 activity in IFN-γ-stimulated brain glial cells. Moreover, these effects of ETYA were independent of PPAR-α. Experiments using actinomycin D revealed that the ETYA-induced increase in MKP-1 mRNA levels reflected an increase in transcript stability. Knockdown experiments using small interfering RNA demonstrated that this increase in MKP-1 mRNA stability depended on HuR, an RNA-binding protein known to promote enhanced mRNA stability. Furthermore, ETYA-induced, HuR-mediated mRNA stabilization resulted from HuR-MKP-1 nucleocytoplasmic translocation, which served to protect MKP-1 mRNA from the mRNA degradation machinery. Conclusion ETYA induces MKP-1 through HuR at the post-transcriptional level in a receptor-independent manner. The mechanism

  2. CCL28 Controls Immunoglobulin (Ig)A Plasma Cell Accumulation in the Lactating Mammary Gland and IgA Antibody Transfer to the Neonate

    OpenAIRE

    Wilson, Eric; Butcher, Eugene C.

    2004-01-01

    The accumulation of immunoglobulin (Ig)A antibody-secreting cells (ASCs) in the lactating mammary gland leads to secretion of antibodies into milk and their passive transfer to the suckling newborn. This transfer of IgA from mother to infant provides transient immune protection against a variety of gastrointestinal pathogens. Here we show that the mucosal epithelial chemokine CCL28 is up-regulated in the mammary gland during lactation and that IgA ASCs from this tissue express CCR10 and migra...

  3. 慈菇对CCl4致大鼠肝纤维化血清cyfra21-1和CEA影响的探讨%The Effect of Sagittaria Agittifolia on Changes of Cyfra21-1 and CEA in Rats of CCl4 Experimental Liver Fibrosis

    Institute of Scientific and Technical Information of China (English)

    吴小南; 汪家梨; 盛健; 黄建宏

    2001-01-01

    目的探讨慈菇对CCl4致大鼠肝纤维化的干预作用.方法对5月龄Wistar大鼠,用CCl4染毒致大鼠形成肝组织纤维化,以ELISA法和放射免疫分析法检测大鼠血清cyfra21-1和CEA的浓度的变化,并观察慈菇的干预效果.结果染毒组大鼠cyfra21-1和CEA明显高于对照组,慈菇可减轻CCl4致大鼠肝纤维化程度并减少cyfra21-1和CEA的产生.结论大鼠肝纤维化后血清cyfra21-1和CEA升高,提示慈菇干预作用的机理值得深入探讨.

  4. Protective effect of Tanreqing injection on acute hepatic injury induced by CCl4 in rats%痰热清注射液对急性肝损伤大鼠的保护作用

    Institute of Scientific and Technical Information of China (English)

    雷扬; 周爱民; 郭涛; 谭烨; 陶艳艳; 刘成海

    2013-01-01

    目的:观察痰热清注射液对四氯化碳(CCl4)诱导大鼠急性肝损伤的保护作用.方法:首先复制CCl4单次染毒模型,100% CCl45mL·kg-1皮下注射,同时设正常对照组,观察染毒3,6h后大鼠肝损伤变化;继而复制CCl4多次染毒肝损伤模型,首次100% CCl45 mL·kg-1,第2次50% CCl4橄榄油溶液2 mL·kg-1,第3次20% CCl4橄榄油溶液2 mL·kg-1皮下注射诱导急性肝损伤模型,首次CCl4染毒6h后分为模型组、甘草酸二铵治疗组、痰热清高、中、低剂量治疗组,连续尾静脉给药7d,同时设正常对照组.观察大鼠体重、肝体比;HE染色观察肝组织炎症病理;试剂盒检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(T.Bil)、直接胆红素(D.Bil)、胆碱酯酶(CHE)、总胆汁酸(TBA)、γ-氨基酰转肽酶(γ-GT)、白蛋白(Alb).结果:单次染毒模型:CCl4单次皮下注射6h后,大鼠血清AST活性与T.Bil含量明显升高,肝组织小叶结构紊乱、肝细胞肿胀明显,呈现明显肝损伤.多次染毒药效实验结果发现:与正常组相比,模型组的ALT,AST与γ-GT活性明显升高(P<0.05),TBA,T.Bil含量明显增加(P<0.05),CHE含量明显降低(P<0.05);HE染色显示,模型组肝小叶结构排列紊乱,肝细胞气球样变明显.与模型组相比,痰热清高、中剂量组与甘草酸二铵组血清肝功能、肝组织炎症病理明显改善,其中痰热清高、中剂量组优于甘草酸二铵组.结论:痰热清注射液具有显著抗CCl4诱导的大鼠急性肝损伤作用.%Objective:To observe the protective effect of Tanreqing injection(TRQ) on carbon tetrachloride-induced acute hepatic injury in rats.Method:Rats were randomly divided into the normal group and the model group,and injected subcutaneously with 100% CCl4 5 mL · kg-1 to establish the single CCl4 infection model,in order to observe the changes in rat liver injury after 3 h and 6 h.Subsequently,the multiple CCl4

  5. Application of gas chromatography to the study of the chemical effects produced by the radiolysis and the 35Cl(n,p)35S reaction on the CCl4

    International Nuclear Information System (INIS)

    In this work the gas radiochromatography, which is essential in the hot atom chemistry is used. By means of this technique the chemical effects of the 35Cl(n,p)35S, and the radiolysis of liquid CCl4 were studied. The samples of liquid CCl4 were capsulated in cuarzo bulbs and were deaereated by several cycles of freeze and pumping in a vacuum line. The sample's irradiation was made in the Triga Mark III Salazar reactor with an approximated flux of 1012n-cm2-s-1 during ten hours. The sample's analysis was made using a gas radiochromatographer composed of a gas chromatographer, proportional flux detector and an adequate electronic system. In this form were obtained the radiochromatographics of the 35S labelled compounds possibly formed by hot atom chemistry and at the same time the hexachloroetane formed by the secondary radiolytic effect of the ionizing radiation on the CCl4 was identified. (author)

  6. 趋化因子CCL11、D-二聚体水平在荨麻疹中的变化及其意义%Alterations and significances of serum D-dimer and chemokine CCL11 levels in urticaria patients

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    目的 探讨荨麻疹患者血清趋化因子CCL11、血浆D-二.聚体水平变化及其与疾病发生发展之间的关系.方法 选择51例急性荨麻疹(Acute Urticaria,AU)、慢性荨麻疹(Chronic Urticaria,CU)患者,根据病情分为轻、中、重度组,并挑选健康成人作为正常对照组.采用酶联免疫吸附试验检测3组荨麻疹患者以及正常对照组血清CCL11及血浆D-二聚体水平,并分析其与荨麻疹症状评分(Urticaria Activity Score,UAS)的相关性.结果 CCL11在轻度、中度和重度荨麻疹中的水平分别是20.12(15.40~23.76)、23.85(11.70~28.25)、18.84(13.10~39.31),组间比较差异无统计学意义(P=0.95).D-二聚体在轻度、中度和重度荨麻疹中的水平分别为935.00(580.00~3 360.00)、2 225.00(850.00~65510.00)、3 865.00(1 235.00~7 820.00),重度和轻度组间比较差异有统计学意义(P=0.04),血清CCL11水平与D-二聚体未见显著相关(r=-0.078,P=0.594).结论 趋化因子CCL11、D-二聚体水平在急、慢性荨麻疹均升高,提示两者可能参与疾病发生,且D-二聚体升高提示疾病活动,可作为病情的监测指标.

  7. Comparative Study of Circulating MMP-7, CCL18, KL-6, SP-A, and SP-D as Disease Markers of Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Hamai, Kosuke; Iwamoto, Hiroshi; Ishikawa, Nobuhisa; Horimasu, Yasushi; Masuda, Takeshi; Miyamoto, Shintaro; Nakashima, Taku; Ohshimo, Shinichiro; Fujitaka, Kazunori; Hamada, Hironobu; Hattori, Noboru; Kohno, Nobuoki

    2016-01-01

    Background. Recent reports indicate that matrix metalloproteinase-7 (MMP-7) and CC-chemokine ligand 18 (CCL18) are potential disease markers of idiopathic pulmonary fibrosis (IPF). The objective of this study was to perform direct comparisons of these two biomarkers with three well-investigated serum markers of IPF, Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), and SP-D. Methods. The serum levels of MMP-7, CCL18, KL-6, SP-A, and SP-D were evaluated in 65 patients with IPF, 31 patients with bacterial pneumonia, and 101 healthy controls. The prognostic performance of these five biomarkers was evaluated in patients with IPF. Results. The serum levels of MMP-7, KL-6, and SP-D in patients with IPF were significantly elevated compared to those in patients with bacterial pneumonia and in the healthy controls. Multivariate survival analysis showed that serum MMP-7 and KL-6 levels were independent predictors in IPF patients. Moreover, elevated levels of both KL-6 and MMP-7 were associated with poorer survival rates in IPF patients, and the combination of both markers provided the best risk discrimination using the C statistic. Conclusions. The present results indicated that MMP-7 and KL-6 were promising prognostic markers of IPF, and the combination of the two markers might improve survival prediction in patients with IPF. PMID:27293304

  8. Effects of undenatured whey protein supplementation on CXCL12- and CCL21-mediated B and T cell chemotaxis in diabetic mice

    Directory of Open Access Journals (Sweden)

    Badr Gamal

    2011-11-01

    Full Text Available Abstract Background Long and persistent uncontrolled diabetes tends to degenerate the immune system and leads to an increased incidence of infection. Whey proteins (WPs enhance immunity during early life and have a protective role in some immune disorders. In this study, the effects of camel WP on the chemotaxis of B and T cells to CXCL12 and CCL21 in diabetic mice were investigated. Results Flow cytometric analysis of the surface expressions of CXCR4 (CXCL12 receptor and CCR7 (CCL21 receptor on B and T cells revealed that the surface expressions of CXCR4 and CCR7 were not significantly altered in diabetic and WP-supplemented diabetic mice compared with control mice. Nevertheless, B and T lymphocytes from diabetic mice were found to be in a stunned state, with a marked and significant (P Conclusion Our data revealed the benefits of WP supplementation in enhancing cytoskeletal rearrangement and chemotaxis in B and T cells, and subsequently improving the immune response in diabetic mice.

  9. The application of new technique for CCL cutting line%覆铜板裁切线新技术的应用研究

    Institute of Scientific and Technical Information of China (English)

    范明锦

    2011-01-01

    基板裁切线设备的功能是将压合后的基板按客户需求裁切成尺寸较小的基板,裁切精度、品质与速度是衡量裁切线设备的关键指标。可通过合理利用传感器技术、变频控制与伺服控制技术、PLC来更好地控制裁切线设备的运行,以达到精度高、品质优、速度快的目的。%The function of CCL cutting line is to cut the CCL into smaller dimension according to the demand of the customers. The precision, quantity and speed of cutting are the pivotal standard. If the sensor technique, frequency control, servo control and PLC which can be applied to running of the cutting line, the goal of higher precision, better quantity and faster speed can be reached.

  10. Increased peroxisome proliferator-activated receptor γ expression levels in visceral adipose tissue, and serum CCL2 and interleukin-6 levels during visceral adipose tissue accumulation.

    Science.gov (United States)

    Yogarajah, Thaneswary; Bee, Yvonne-Tee Get; Noordin, Rahmah; Yin, Khoo Boon

    2015-01-01

    This study was conducted to determine the mRNA and protein expression levels of peroxisome proliferator-activated receptors (PPARs) in visceral adipose tissue, as well as serum adipokine levels, in Sprague Dawley rats. The rats were fed either a normal (control rats) or excessive (experimental rats) intake of food for 8 or 16 weeks, then sacrificed, at which time visceral and subcutaneous adipose tissues, as well as blood samples, were collected. The mRNA and protein expression levels of PPARs in the visceral adipose tissues were determined using reverse transcription-polymerase chain reaction and Western blotting, respectively. In addition, the levels of adipokines in the serum samples were determined using commercial ELISA kits. The results revealed that at 8 weeks, the mass of subcutaneous adipose tissue was higher than that of the visceral adipose tissue in the experimental rats, but the reverse occurred at 16 weeks. Furthermore, at 16 weeks the experimental rats exhibited an upregulation of PPARγ mRNA and protein expression levels in the visceral adipose tissues, and significant increases in the serum levels of CCL2 and interleukin (IL)-6 were observed, compared with those measured at 8 weeks. In conclusion, this study demonstrated that the PPARγ expression level was likely correlated with serum levels of CCL2 and IL-6, molecules that may facilitate visceral adipose tissue accumulation. In addition, the levels of the two adipokines in the serum may be useful as surrogate biomarkers for the expression levels of PPARγ in accumulated visceral adipose tissues.

  11. IL-17A synergistically enhances TNFα-induced IL-6 and CCL20 production in 3T3-L1 adipocytes.

    Science.gov (United States)

    Shinjo, Takanori; Iwashita, Misaki; Yamashita, Akiko; Sano, Tomomi; Tsuruta, Mitsudai; Matsunaga, Hiroaki; Sanui, Terukazu; Asano, Tomoichiro; Nishimura, Fusanori

    2016-08-19

    Interleukin-17A (IL-17A) is known to induce inflammatory responses and to be involved in the pathogenesis of not only autoimmune diseases, but also several metabolic and infectious diseases. In this study, IL-17A is shown to induce IL-6 expression in 3T3-L1 mature adipocytes. Interestingly, we found that IL-17A synergistically amplified TNFα-induced secretion of IL-6 and upregulation of IL-17RA expression in 3T3-L1 adipocytes. Its synergistic effects on IL-6 production were inhibited by pre-treatment with inhibitors of IκBα and JNK. Furthermore, IL-17A cooperatively enhanced LPS-mediated IL-6 production in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. In addition, IL-17A also enhanced CCL20 production in 3T3-L1 adipocytes stimulated with TNFα or co-cultured with LPS-stimulated RAW macrophages. In high-fat diet-fed mouse epididymal adipose tissues, IL-17RA and RORγt mRNA levels were significantly increased and the serum level of CCL20 was also upregulated. Taken together, these data show that, in adipose tissues, IL-17A contributes to exacerbating insulin resistance-enhancing IL-6 production and promotes the infiltration of Th17 cells in cooperation with TNFα; these findings represent a novel hypothesis for the association between IL-17A-producing cells and type 2 diabetes. PMID:27311858

  12. Hepatoprotective activity of petroleum ether, diethyl ether, and methanol extract of Scoparia dulcis L. against CCl4-induced acute liver injury in mice

    Directory of Open Access Journals (Sweden)

    Praveen T

    2009-01-01

    Full Text Available Objectives: The present study was aimed at assessing the hepatoprotective activity of 1:1:1 petroleum ether, diethyl ether, and methanol (PDM extract of Scoparia dulcis L. against carbon tetrachloride-induced acute liver injury in mice. Materials and Methods: The PDM extract (50, 200, and 800 mg/kg, p.o. and standard, silymarin (100 mg/kg, p.o were tested for their antihepatotoxic activity against CCl4-induced acute liver injury in mice. The hepatoprotective activity was evaluated by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total proteins in serum, glycogen, lipid peroxides, superoxide dismutase, and glutathione reductase levels in liver homogenate and by histopathological analysis of the liver tissue. In addition, the extract was also evaluated for its in vitro antioxidant activity using 1, 1-Diphenyl-2-picrylhydrazyl scavenging assay. Results: The extract at the dose of 800 mg/kg, p.o., significantly prevented CCl4-induced changes in the serum and liver biochemistry (P < 0.05 and changes in liver histopathology. The above results are comparable to standard, silymarin (100 mg/kg, p.o.. In the in vitro 1, 1-diphenyl-2-picrylhydrazyl scavenging assay, the extract showed good free radical scavenging potential (IC 50 38.9 ± 1.0 µg/ml. Conclusions: The results of the study indicate that the PDM extract of Scoparia dulcis L. possesses potential hepatoprotective activity, which may be attributed to its free radical scavenging potential, due to the terpenoid constituents.

  13. Lincoln Laboratory Grid

    Data.gov (United States)

    Federal Laboratory Consortium — The Lincoln Laboratory Grid (LLGrid) is an interactive, on-demand parallel computing system that uses a large computing cluster to enable Laboratory researchers to...

  14. NASA Space Radiation Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory is a NASA funded facility, delivering heavy ion beams to a target area where scientists...

  15. Laboratory-acquired brucellosis

    DEFF Research Database (Denmark)

    Fabiansen, C.; Knudsen, J.D.; Lebech, A.M.

    2008-01-01

    Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9......Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9...

  16. Laboratory of Chemical Physics

    Data.gov (United States)

    Federal Laboratory Consortium — Current research in the Laboratory of Chemical Physics is primarily concerned with experimental, theoretical, and computational problems in the structure, dynamics,...

  17. Embedded Processor Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Embedded Processor Laboratory provides the means to design, develop, fabricate, and test embedded computers for missile guidance electronics systems in support...

  18. COGNITIVE PERFORMANCE LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory conducts basic and applied human research studies to characterize cognitive performance as influenced by militarily-relevant contextual and physical...

  19. Optical Remote Sensing Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Optical Remote Sensing Laboratory deploys rugged, cutting-edge electro-optical instrumentation for the collection of various event signatures, with expertise in...

  20. Intelligent Optics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Intelligent Optics Laboratory supports sophisticated investigations on adaptive and nonlinear optics; advancedimaging and image processing; ground-to-ground and...

  1. Environmental Microbiology Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Environmental Microbiology Laboratory, located in Bldg. 644 provides a dual-gas respirometer for measurement of oxygen consumption and carbon dioxide evolution...

  2. ANALYTICAL MICROBIOLOGY LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory contains equipment that performs a broad array of microbiological analyses for pathogenic and spoilage microorganisms. It performs challenge studies...

  3. Neural Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  4. Central Laboratories Services

    Data.gov (United States)

    Federal Laboratory Consortium — The TVA Central Laboratories Services is a comprehensive technical support center, offering you a complete range of scientific, engineering, and technical services....

  5. Tactical Systems Integration Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Tactical Systems Integration Laboratory is used to design and integrate computer hardware and software and related electronic subsystems for tactical vehicles....

  6. Virtual Training Devices Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Virtual Training Devices (VTD) Laboratory at the Life Cycle Software Engineering Center, Picatinny Arsenal, provides a software testing and support environment...

  7. FOOD SAFETY TESTING LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory develops screening assays, tests and modifies biosensor equipment, and optimizes food safety testing protocols for the military and civilian sector...

  8. Space Weather Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Space Weather Computational Laboratory is a Unix and PC based modeling and simulation facility devoted to research analysis of naturally occurring electrically...

  9. Composites Characterization Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The purpose of the Composites Characterization Laboratory is to investigate new and/or modified matrix materials and fibers for advanced composite applications both...

  10. Rapid Prototyping Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The ARDEC Rapid Prototyping (RP) Laboratory was established in December 1992 to provide low cost RP capabilities to the ARDEC engineering community. The Stratasys,...

  11. Engineered Natural Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — With its pressure vessels that simulate the pressures and temperatures found deep underground, NETL’s Engineered Natural Systems Laboratory in Pittsburgh, PA, gives...

  12. [Theme: Using Laboratories.

    Science.gov (United States)

    Pritchard, Jack; Braker, Clifton

    1982-01-01

    Pritchard discusses the opportunities for applied learning afforded by laboratories. Braker describes the evaluation of cognitive, affective, and psychomotor skills in the agricultural mechanics laboratory. (SK)

  13. Vehicle Development Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Supports the development of prototype deployment platform vehicles for offboard countermeasure systems. DESCRIPTION: The Vehicle Development Laboratory is...

  14. Fuels Processing Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — NETL’s Fuels Processing Laboratory in Morgantown, WV, provides researchers with the equipment they need to thoroughly explore the catalytic issues associated with...

  15. Thermogravimetric Analysis Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — At NETL’s Thermogravimetric Analysis Laboratory in Morgantown, WV, researchers study how chemical looping combustion (CLC) can be applied to fossil energy systems....

  16. Study on Protective Effect of Mongolian Medicine Lomatogonium rotatum Water Extract against Acute Liv-er Injury in Mice Induced by D-GlaN and CCl4%蒙药肋柱花水提物对D-GlaN和CCl4致小鼠急性肝损伤的保护作用研究

    Institute of Scientific and Technical Information of China (English)

    包明兰; 巴根那; 辛颖; 白梅荣; 何那拉

    2016-01-01

    目的:研究蒙药肋柱花水提物对D-氨基半乳糖胺(D-GlaN)和四氯化碳(CCl4)致小鼠急性肝损伤的保护作用.方法:取60只小鼠随机分为正常(生理盐水)组、D-GlaN模型(生理盐水)组、阳性对照(葵花护肝片,0.56 g/kg)组和肋柱花水提物高、中、低剂量[3、1.5、0.75 g(生药)/kg]组,每组10只,ig给药,qd,连续23 d;末次给药30 min后,除正常组外,其余各组小鼠ip D-GlaN复制急性肝损伤模型.检测小鼠血清中天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)活性和胆碱酯酶(CHE)含量,计算肝脏指数,对肝组织病理形态进行观察并评分.另取60只小鼠,除造模方法(ig 0.1%CCl4)不同外,按相同分组、给药及指标检测方法进行实验.结果:与正常组比较,两种模型组小鼠肝细胞明显坏死或变性,病理评分升高;血清中AST、ALT、ALP活性升高,CHE含量减少;且D-GlaN模型组肝脏指数升高、CCl4模型组肝脏指数降低(P<0.05).与D-GlaN模型组比较,肋柱花水提物各剂量组小鼠血清AST、ALT、ALP活性及肝脏指数降低,CHE含量增加(P<0.05);肝组织病理形态改善,评分降低.与CCl4模型组比较,肋柱花水提物低剂量组小鼠血清ALT活性降低、CHE含量增加,肝脏指数升高;肋柱花水提物中剂量组小鼠血清CHE含量减少,肝脏指数升高;肋柱花水提物高剂量组小鼠血清AST、ALT、ALP活性降低,CHE含量增加(P<0.05).肋柱花水提物各剂量组小鼠肝组织病理形态都得到一定改善,评分降低.结论:肋柱花水提物对D-GlaN或CCl4致小鼠急性肝损伤有一定保护作用.%OBJECTIVE:To study the protective effects of Mongolian medicine Lomatogonium rotatum water extract against acute liver injury in mice caused by D-GlaN and CCl4. METHODS:60 mice were randomly divided into normal group(normal sa-line),D-GlaN model group(normal saline),positive control group(Kuihua hugan tablet,0.56 g/kg)and L. rotatum water extract high

  17. Energy Materials Research Laboratory (EMRL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Energy Materials Research Laboratory at the Savannah River National Laboratory (SRNL) creates a cross-disciplinary laboratory facility that lends itself to the...

  18. Pd(OAc)2与PPh3在氯代甲烷中的反应研究%STUDY OF THE REACTION OF Pd(OAc)2 WITH PPh3 IN CCl4

    Institute of Scientific and Technical Information of China (English)

    韦凤萍; 黄永仁; 冯良波; 汪汉卿

    2001-01-01

    The complex Pd(PPh3)2Cl2*CCl4 has been prepared by treatment of Pd(OAc)2 with PPh3 in CCl4. 1H NMR, 31P NMR, data are given. The molecular structure of Pd(PPh3)2Cl2 has been determined by single crystal X-rays diffraction. The reaction mechanism is tentatively proposed and discussed. Radicals were trapped by PBN. This reaction was proved to be a free radical reaction by EPR-ST method. The solvent CCl4 participated in the reaction.%用Pd(OAc)2与PPh3在四氯甲烷中反应,合成了配合物PdCl2(PPh3)2*CCl4,得到单晶,用X-ray衍射确定了单晶结构.应用电子顺磁共振-自旋捕获(EPR-ST)技术研究了其反应的机理.捕获了含碳自由基中间体,提出了反应机理.

  19. Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors

    DEFF Research Database (Denmark)

    Damgaard, C; Kantarci, A; Holmstrup, P;

    2016-01-01

    healthy controls release the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor α (TNF-α), the chemokine (C-X-C motif) ligand 8 (CXCL8; also known as IL-8) and chemokine (C-C motif) ligand 2 (CCL2; also known as monocyte chemotactic protein-1) and intracellular reactive oxygen species...... of neutrophils were investigated. RESULTS: Upon stimulation with P. gingivalis, neutrophils from subjects with LAgP and healthy controls released similar quantities of IL-6, TNF-α, CXCL8, CCL2 and intracellular ROS. The presence of RBCs amplified the release of IL-6, TNF-α and CCL2 statistically significant...... in both groups, but reduced the generation of ROS in the group of healthy controls, and showed a similar tendency in the group of subjects with LAgP. RvE1 had no impact on the production of intracellular ROS, TNF-α, IL-6, CXCL8 and CCL2 by neutrophils from either group, but tended to reduce the generation...

  20. Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia

    Directory of Open Access Journals (Sweden)

    Victor Manuel Blanco-Alvarez

    2015-01-01

    Full Text Available Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO. Male rats were grouped as follows: (1 Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days; (2 Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3 CCAO, rats with CCAO only; (4 Sham group, rats with mock CCAO; and (5 untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

  1. Biosynthesis of silver nanoparticles from Premna serratifolia L. leaf and its anticancer activity in CCl4-induced hepato-cancerous Swiss albino mice

    Science.gov (United States)

    Arockia John Paul, J.; Karunai Selvi, B.; Karmegam, N.

    2015-11-01

    In this study, we report the biosynthesis of silver nanoparticles using the ethanolic leaf powder extract of Premna serratifolia L. and its anticancer activity in carbon tetra chloride (CCl4)-induced liver cancer in Swiss albino mice (Balb/c). The synthesized silver nanoparticles were characterized by SEM, FTIR and XRD analyses. The Debye-Scherrer equation was used to calculate particle size and the average size of silver nanoparticles synthesized from P. serratifolia leaf extract was 22.97 nm. The typical pattern revealed that the sample contained cubic structure of silver nanoparticles. FTIR analysis confirmed that the bioreduction of silver ions to silver nanoparticles is due to reduction by capping material of the plant extract. The silver nanoparticles of P. serratifolia leaf extract were effective in treating liver cancer in Swiss albino mice when compared with P. serratifolia leaf extract with isoleucine.

  2. CCl0/H2O/CTAB乳状液的稳定性研究%STUDY ON STABILITY OF EMULSION COMPOSED OF CARBON TETRACHLORIDE/WATER/CETYLTRIMETHYLAMMONIUM BROMIDE

    Institute of Scientific and Technical Information of China (English)

    倪良; 蒋文华; 韩世钧

    2001-01-01

    制备了不同组成的CCl4/H2O/十六烷基三甲基溴化铵(CTAB)乳状液,用电导法测定了含与不含添加剂(正已醇和水杨酸钠)条件下,乳状液富油相区不同时间的电导率.为了寻找乳状液的稳定性与电导率之间的关系,提出了富油相增比电导率的概念,并由增比电导率与时间的关系讨论了乳状液的稳定性.

  3. Dynamics of heavy-Rydberg ion-pair formation in K(14p,20p)-SF6, CCl4 collisions

    Science.gov (United States)

    Wang, C. H.; Kelley, M.; Buathong, S.; Dunning, F. B.

    2014-06-01

    The dynamics of formation of heavy-Rydberg ion-pair states through electron transfer in K(np)-SF6, CCl4 collisions is examined by measuring the velocity, angular, and binding energy distributions of the product ion pairs. The results are analyzed with the aid of a Monte Carlo collision code that models both the initial electron capture and the subsequent evolution of the ion pairs. The model simulations are in good agreement with the experimental data and highlight the factors such as Rydberg atom size, the kinetic energy of relative motion of the Rydberg atom and target particle, and (in the case of attaching targets that dissociate) the energetics of dissociation that can be used to control the properties of the product ion-pair states.

  4. Effects of carbon dioxide and nitrogen on adhesive growth and expressions of E-cadherin and VEGF of human colon cancer cell CCL-228

    Institute of Scientific and Technical Information of China (English)

    Kai-Lin Cai; Guo-Bing Wang; Li-Juan Xiong

    2003-01-01

    AIM: To study the effects of carbon dioxide on the metastatic capability of cancer cells, and to compare them with that of nitrogen.METHODS: The colon cancer cell CCL-228 was treated with 100 % carbon dioxide or nitrogen at different time points and then cultured under normal condition. Twelve hours after the treatment, the survival rates of suspension cells and the expressions of e-cadherin and VEGF were examined.RESULTS: After 60 min of carbon dioxide and longer time of nitrogen treatment, the suspended cells increased and the expression of e-cadherin decreased while the expression of VEGF was enhanced significantly. And the effects of nitrogen were similar to, but weaker than, those of carbon dioxide.CONCLUSION: Carbon dioxide may improve the metastatic capability of cancer cells and its effects are significantly stronger than that of nitrogen. A sequential use of carbon dioxide and nitrogen in pneumoperitoneum may take the advantage of both gases.

  5. SCAI expert consensus statement: Evaluation, management, and special considerations of cardio-oncology patients in the cardiac catheterization laboratory (Endorsed by the Cardiological Society of India, and Sociedad Latino Americana de Cardiologıa Intervencionista).

    Science.gov (United States)

    Iliescu, Cezar; Grines, Cindy L; Herrmann, Joerg; Yang, Eric H; Cilingiroglu, Mehmet; Charitakis, Konstantinos; Hakeem, Abdul; Toutouzas, Konstantinos; Leesar, Massoud A; Marmagkiolis, Konstantinos

    2016-04-01

    In the United States alone, there are currently approximately 14.5 million cancer survivors, and this number is expected to increase to 20 million by 2020. Cancer therapies can cause significant injury to the vasculature, resulting in angina, acute coronary syndromes (ACS), stroke, critical limb ischemia, arrhythmias, and heart failure, independently from the direct myocardial or pericardial damage from the malignancy itself. Consequently, the need for invasive evaluation and management in the cardiac catheterization laboratory (CCL) for such patients has been increasing. In recognition of the need for a document on special considerations for cancer patients in the CCL, the Society for Cardiovascular Angiography and Interventions (SCAI) commissioned a consensus group to provide recommendations based on the published medical literature and on the expertise of operators with accumulated experience in the cardiac catheterization of cancer patients.

  6. Eimeria ninakohlyakimovae induces NADPH oxidase-dependent monocyte extracellular trap formation and upregulates IL-12 and TNF-α, IL-6 and CCL2 gene transcription.

    Science.gov (United States)

    Pérez, D; Muñoz, M C; Molina, J M; Muñoz-Caro, T; Silva, L M R; Taubert, A; Hermosilla, C; Ruiz, A

    2016-08-30

    Extracellular trap (ET) formation has been demonstrated as novel effector mechanism against diverse pathogens in polymorphonuclear neutrophils (PMN), eosinophils, mast cells, macrophages and recently also in monocytes. In the current study, we show that E. ninakohlyakimovae triggers the deliverance of monocyte-derived ETs in vitro. Fluorescence illustrations as well as scanning electron microscopy (SEM) analyses showed that monocyte-derived ET formation was rapidly induced upon exposure to viable sporozoites, sporocysts and oocysts of E. ninakohlyakimovae. Classical features of monocyte-released ETs were confirmed by the co-localization of extracellular DNA adorned with myeloperoxidase (MPO) and histones (H3) in parasite-entrapping structures. The treatment of caprine monocyte ET structures with NADPH oxidase inhibitor diphenylene iodondium (DPI) significantly reduced ETosis confirming the essential role of reactive oxygen species (ROS) in monocyte mediated ETs formation. Additionally, co-culture of monocytes with viable sporozoites and soluble oocyst antigen (SOA) induced distinct levels of cytokine and chemokine gene transcription. Thus, the transcription of genes encoding for IL-12 and TNF-α was significantly upregulated after sporozoite encounter. In contrast IL-6 and CCL2 gene transcripts were rather weakly induced by parasites. Conversely, SOA only induced the up-regulation of IL-6 and CCL2 gene transcription, and failed to enhance transcripts of IL-12 and TNF-α in vitro. We here report on monocyte-triggered ETs as novel effector mechanism against E. ninakohlyakimovae. Our results strongly suggest that monocyte-mediated innate immune reactions might play an important role in early host immune reactions against E. ninakohlyakimovae in goats. PMID:27523951

  7. Aircraft Fire Protection Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Navy Aircraft Protection Laboratory provides complete test support for all Navy air vehicle fire protection systems. The facility allows for the simulation of a...

  8. Energetics Laboratory Facilities

    Data.gov (United States)

    Federal Laboratory Consortium — These energetic materials laboratories are equipped with explosion proof hoods with blow out walls for added safety, that are certified for safe handling of primary...

  9. Laboratory of Biological Modeling

    Data.gov (United States)

    Federal Laboratory Consortium — The Laboratory of Biological Modeling is defined by both its methodologies and its areas of application. We use mathematical modeling in many forms and apply it to...

  10. Laboratory Demographics Lookup Tool

    Data.gov (United States)

    U.S. Department of Health & Human Services — This website provides demographic information about laboratories, including CLIA number, facility name and address, where the laboratory testing is performed, the...

  11. Building the Korogwe Laboratory

    DEFF Research Database (Denmark)

    Knudsen, Jakob; von Seidlein, Lorenz; Richard, Jean Pierre

    2011-01-01

    An illustrated description of the building of a biomedical research laboratory in Korogwe, Tanzania.......An illustrated description of the building of a biomedical research laboratory in Korogwe, Tanzania....

  12. Geological Services Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Researchers use computed tomography (CT) scanners at NETL’s Geological Services Laboratory in Morgantown, WV, to peer into geologic core samples to determine how...

  13. Clinical Laboratory Fee Schedule

    Data.gov (United States)

    U.S. Department of Health & Human Services — Outpatient clinical laboratory services are paid based on a fee schedule in accordance with Section 1833(h) of the Social Security Act. The clinical laboratory fee...

  14. Electro-Deposition Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The electro-deposition laboratory can electro-deposit various coatings onto small test samples and bench level prototypes. This facility provides the foundation for...

  15. Protective Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory is a 40 by 28 by 9 foot facility that is equipped with tools for the development of various items of control technology related to the transmission...

  16. Moriah Wind System Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The Moriah Wind System Laboratory provides in-service support for the more than 50 U.S. Navy, U.S. Coast Guard and Military Sealift Command ships on which...

  17. Aquatic Research Laboratory (ARL)

    Data.gov (United States)

    Federal Laboratory Consortium — Columbia River and groundwater well water sources are delivered to the Aquatic Research Laboratory (ARL), where these resources are used to conduct research on fish...

  18. FLEXIBLE FOOD PACKAGING LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory contains equipment to fabricate and test prototype packages of many types and sizes (e.g., bags, pouches, trays, cartons, etc.). This equipment can...

  19. Mechanical Testing Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — NETL’s Mechanical Testing Laboratory in Albany, OR, helps researchers investigate materials that can withstand the heat and pressure commonly found in fossil energy...

  20. High Bay Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory is a specially constructed facility with elevated (37 feet) ceilings and an overhead catwalk, and which is dedicated to research efforts in reducing...

  1. Space Systems Laboratory (SSL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Space Systems Laboratory (SSL) is part of the Aerospace Engineering Department and A. James Clark School of Engineering at the University of Maryland in College...

  2. Experiences with Remote Laboratories

    OpenAIRE

    Andrew Nafalski; Ozdemir Gol; Zorica Nedic; Jan Machotka; José M. M. Ferreira; Ingvar Gustavsson

    2010-01-01

    The paper reports on experiences of academics and students involved in using remote engineering laboratories both when students work individually or collaboratively with others on the experiments. Positives and negatives are highlighted and are contrasted with expectations of what the remote laboratories can bring into pedagogical environments. Recommendations and conclusions follow on how to better use the remote laboratories in teaching.

  3. Laboratory Activities in Israel

    Science.gov (United States)

    Mamlok-Naaman, Rachel; Barnea, Nitza

    2012-01-01

    Laboratory activities have long had a distinctive and central role in the science curriculum, and science educators have suggested that many benefits accrue from engaging students in science laboratory activities. Many research studies have been conducted to investigate the educational effectiveness of laboratory work in science education in…

  4. Good Laboratory Practice

    Science.gov (United States)

    Hadjicostas, Evsevios

    The principles of Good Laboratory Practice (GLP) in conjunction with the principles of Total Quality Management (see chapter 6) ensure the quality and reliability of the laboratory results, which in turn help to ensure the protection of the environment and human health and safety. A step further is the accreditation of laboratories to ISO 17025 (see chapter 2) to perform specified activities.

  5. Improvement and optimization of CCl4 induced liver cirrhosis rats model accompanied with ascites%四氯化碳诱导大鼠肝硬化腹水模型的改进与优化

    Institute of Scientific and Technical Information of China (English)

    唐倩; 王卓; 赵雄; 吕茂贞; 吕茂民; 章金刚

    2012-01-01

    Objective To establish a stable, homogeneous, well-tolerated and efficient protocol to induce rat cirrhosis models accompanied with ascites using an improved carbon tetrachloride(CCl4) combined with phenobarbital sodium and alcohol method, thus establishing a basis for serum albumin effectiveness evaluation test. Methods Ninety male Wistar rats were randomly divided into five groups: blank control group containing 10 rats, CCl4 group, CC14 + phenobarbital sodium group, CCl4 + alcohol group and CC14 + phenobarbital sodium + alcohol group containing 20 rats respectively as model groups. The control group was given normal drinking water and injected with olive oil intraperitoneally. Rats in model groups were given different drinking water and an intraperitoneal injection of CC14 in a 2: 3 mixture with olive oil. The drugs given intraperitoneally were all at a dose of 2 ml/kg body mass, twice weekly for 12 weeks. We further measured the body mass and abdominal circumference, and tested the biochemical liver function indices as well as the colloid osmotic pressure ( COP) to evaluate the different processes in these groups. At the end of the induced operation the randomly selected rats in each group were sacrificed, and a section of right liver lobe was obtained and examined by histopathological method. The statistical analysis data were performed. Results Cirrhosis accompanied with ascites developed in all model groups between 8 and 12 weeks. However, at the end of the eighth week, rats in CCl4 + phenobarbital sodium + alcohol group were firstly detected to correspond with the model standards, CC14 + phenobarbital sodium group and CC14 + alcohol group were detected to have positive model signs at the ninth week. Only at the tenth week a few rats appeared to have ascites in CC14 group. All the model groups showed significant differences in the biochemical liver function indices, COP and body mass than the rats in control group, and the most significant differences were

  6. Skylab mobile laboratory

    Science.gov (United States)

    Primeaux, G. R.; Larue, M. A.

    1975-01-01

    The Skylab mobile laboratory was designed to provide the capability to obtain necessary data on the Skylab crewmen 30 days before lift-off, within 1 hour after recovery, and until preflight physiological baselines were reattained. The mobile laboratory complex consisted of six laboratories that supported cardiovascular, metabolic, nutrition and endocrinology, operational medicine, blood, and microbiology experiments; a utility package; and two shipping containers. The objectives and equipment requirements of the Skylab mobile laboratory and the data acquisition systems are discussed along with processes such as permanently mounting equipment in the individual laboratories and methods of testing and transporting the units. The operational performance, in terms of amounts of data collected, and the concept of mobile laboratories for medical and scientific experiments are evaluated. The Skylab mobile laboratory succeeded in facilitating the data collection and sample preservation associated with the three Skylab manned flights.

  7. Personalized laboratory medicine

    DEFF Research Database (Denmark)

    Pazzagli, M.; Malentacchi, F.; Mancini, I.;

    2015-01-01

    diagnostic tools and expertise and commands proper state-of-the-art knowledge about Personalized Medicine and Laboratory Medicine in Europe, the joint Working Group "Personalized Laboratory Medicine" of the EFLM and ESPT societies compiled and conducted the Questionnaire "Is Laboratory Medicine ready...... for the era of Personalized Medicine?". 48 laboratories from 18 European countries participated at this survey. The answers of the participating Laboratory Medicine professionals indicate that they are aware that Personalized Medicine can represent a new and promising health model. Whereas they are aware...... that Laboratory Medicine should play a key role to support the implementation of Personalized Medicine in the clinical settings, the participants of this survey think that the current organization of the Laboratory Medicine needs additional/relevant implementations such as: 1. New technological Facilities...

  8. Heat Flux Instrumentation Laboratory (HFIL)

    Data.gov (United States)

    Federal Laboratory Consortium — Description: The Heat Flux Instrumentation Laboratory is used to develop advanced, flexible, thin film gauge instrumentation for the Air Force Research Laboratory....

  9. Optics/Optical Diagnostics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Optics/Optical Diagnostics Laboratory supports graduate instruction in optics, optical and laser diagnostics and electro-optics. The optics laboratory provides...

  10. pH-Responsive Tumor-Targetable Theranostic Nanovectors Based on Core Crosslinked (CCL Micelles with Fluorescence and Magnetic Resonance (MR Dual Imaging Modalities and Drug Delivery Performance

    Directory of Open Access Journals (Sweden)

    Sidan Tian

    2016-06-01

    Full Text Available The development of novel theranostic nanovectors is of particular interest in treating formidable diseases (e.g., cancers. Herein, we report a new tumor-targetable theranostic agent based on core crosslinked (CCL micelles, possessing tumor targetable moieties and fluorescence and magnetic resonance (MR dual imaging modalities. An azide-terminated diblock copolymer, N3-POEGMA-b-P(DPA-co-GMA, was synthesized via consecutive atom transfer radical polymerization (ATRP, where OEGMA, DPA, and GMA are oligo(ethylene glycolmethyl ether methacrylate, 2-(diisopropylaminoethyl methacrylate, and glycidyl methacrylate, respectively. The resulting diblock copolymer was further functionalized with DOTA(Gd (DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakisacetic acid or benzaldehyde moieties via copper(I-catalyzed alkyne-azide cycloaddition (CuAAC chemistry, resulting in the formation of DOTA(Gd-POEGMA-b-P(DPA-co-GMA and benzaldehyde-POEGMA-b-P(DPA-co-GMA copolymers. The resultant block copolymers co-assembled into mixed micelles at neutral pH in the presence of tetrakis[4-(2-mercaptoethoxyphenyl]ethylene (TPE-4SH, which underwent spontaneous crosslinking reactions with GMA residues embedded within the micellar cores, simultaneously switching on TPE fluorescence due to the restriction of intramolecular rotation. Moreover, camptothecin (CPT was encapsulated into the crosslinked cores at neutral pH, and tumor-targeting pH low insertion peptide (pHLIP, sequence: AEQNPIYWARYADWLFTTPLLLLDLALLVDADEGTCG moieties were attached to the coronas through the Schiff base chemistry, yielding a theranostic nanovector with fluorescence and MR dual imaging modalities and tumor-targeting capability. The nanovectors can be efficiently taken up by A549 cells, as monitored by TPE fluorescence. After internalization, intracellular acidic pH triggered the release of loaded CPT, killing cancer cells in a selective manner. On the other hand, the nanovectors labeled with DOTA

  11. Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver fibrosis in rats: role of ASH1 and EZH2 methyltransferases repression.

    Directory of Open Access Journals (Sweden)

    Hussein Atta

    Full Text Available Hepatocyte growth factor (HGF gene transfer inhibits liver fibrosis by regulating aberrant cellular functions, while mutant matrix metalloproteinase-9 (mMMP-9 enhances matrix degradation by neutralizing the elevated tissue inhibitor of metalloproteinase-1 (TIMP-1. It was shown that ASH1 and EZH2 methyltransferases are involved in development of liver fibrosis; however, their role in the resolution phase of liver fibrosis has not been investigated. This study evaluated the role of ASH1 and EZH2 in two mechanistically different therapeutic modalities, HGF and mMMP-9 gene transfer in CCl4 induced rat liver fibrosis. Liver fibrosis was induced in rats with twice a week intraperitoneal injection of CCl4 for 8 weeks. Adenovirus vectors encoding mMMP-9 or HGF genes were injected through tail vein at weeks six and seven and were sacrificed one week after the second injection. A healthy animal group was likewise injected with saline to serve as a negative control. Rats treated with mMMP-9 showed significantly lower fibrosis score, less Sirius red stained collagen area, reduced hydroxyproline and ALT concentration, decreased transforming growth factor beta 1 (TGF-β1 mRNA and lower labeling indices of α smooth muscle actin (α-SMA and proliferating cell nuclear antigen (PCNA stained cells compared with HGF- or saline-treated rats. Furthermore, TIMP-1 protein expression in mMMP-9 group was markedly reduced compared with all fibrotic groups. ASH1 and EZH2 protein expression was significantly elevated in fibrotic liver and significantly decreased in mMMP-9- and HGF-treated compared to saline-treated fibrotic livers with further reduction in the mMMP-9 group.Gene transfer of mMMP-9 and HGF reduced liver fibrosis in rats. ASH1 and EZH2 methyltransferases are significantly reduced in mMMP-9 and HGF treated rats which underlines the central role of these enzymes during fibrogenesis. Future studies should evaluate the role of selective pharmacologic inhibitors

  12. Head Impact Laboratory (HIL)

    Data.gov (United States)

    Federal Laboratory Consortium — The HIL uses testing devices to evaluate vehicle interior energy attenuating (EA) technologies for mitigating head injuries resulting from head impacts during mine/...

  13. Shallow Water Acoustic Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Supports experimental research where high-frequency acoustic scattering and surface vibration measurements of fluid-loaded and non-fluid-loaded structures...

  14. Materials Behavior Research Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The purpose is to evaluate mechanical properties of materials including metals, intermetallics, metal-matrix composites, and ceramic-matrix composites under typical...

  15. Metallurgical Research Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The purpose is to increase basic knowledge of metallurgical processing for controlling the microstructure and mechanical properties of metallic aerospace alloys and...

  16. Laboratory Astrophysics White Paper

    Science.gov (United States)

    Brickhouse, Nancy; Federman, Steve; Kwong, Victor; Salama, Farid; Savin, Daniel; Stancil, Phillip; Weingartner, Joe; Ziurys, Lucy

    2006-01-01

    Laboratory astrophysics and complementary theoretical calculations are the foundations of astronomical and planetary research and will remain so for many generations to come. From the level of scientific conception to that of the scientific return, it is our understanding of the underlying processes that allows us to address fundamental questions regarding the origins and evolution of galaxies, stars, planetary systems, and life in the cosmos. In this regard, laboratory astrophysics is much like detector and instrument development at NASA and NSF; these efforts are necessary for the astronomical research being funded by the agencies. The NASA Laboratory Astrophysics Workshop met at the University of Nevada, Las Vegas (UNLV) from 14-16 February, 2006 to identify the current laboratory data needed to support existing and future NASA missions and programs in the Astrophysics Division of the Science Mission Directorate (SMD). Here we refer to both laboratory and theoretical work as laboratory astrophysics unless a distinction is necessary. The format for the Workshop involved invited talks by users of laboratory data, shorter contributed talks and poster presentations by both users and providers that highlighted exciting developments in laboratory astrophysics, and breakout sessions where users and providers discussed each others' needs and limitations. We also note that the members of the Scientific Organizing Committee are users as well as providers of laboratory data. As in previous workshops, the focus was on atomic, molecular, and solid state physics.

  17. Flying Electronic Warfare Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Provides NP-3D aircraft host platforms for Effectiveness of Navy Electronic Warfare Systems (ENEWS) Program antiship missile (ASM) seeker simulators used...

  18. High Temperature Materials Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The High Temperature Materials Lab provides the Navy and industry with affordable high temperature materials for advanced propulsion systems. Asset List: Arc Melter...

  19. Free Surface Hydrodynamics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Investigates processes and interactions at the air-sea interface, and compares measurements to numerical simulations and field data. Typical phenomena of...

  20. Biochemical Neuroscience Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This biochemistry lab is set up for protein analysis using Western blot, enzyme linked immunosorbent assays, immunohistochemistry, and bead-based immunoassays. The...

  1. Applied Neuroscience Laboratory Complex

    Data.gov (United States)

    Federal Laboratory Consortium — Located at WPAFB, Ohio, the Applied Neuroscience lab researches and develops technologies to optimize Airmen individual and team performance across all AF domains....

  2. Virtual Reality Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Performs basic and applied research in interactive 3D computer graphics, including visual analytics, virtual environments, and augmented reality (AR). The...

  3. DA-9601, a standardized extract of Artemisia asiatica, blocks TNF-α-induced IL-8 and CCL20 production by inhibiting p38 kinase and NF-κB pathways in human gastric epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Suck-Chei Choi; Kang-Min Lee; Won-Jung Lee; Jae-Sik Park; Chang-Yell Shin; Tae-Young Oh; Chang-Duk Jun; Eun-Ju Choi; Hyun-Mee Oh; SungGa Lee; Jeong-Kun Lee; Meung-Su Lee; Yong-Il Shin; Suck-Jun Choi; Jeong-Ryong Chae

    2006-01-01

    AIM: To investigate whether, or how, DA-9601, which is a new gastroprotective agent, inhibits TNF-α-induced inflammatory signals in gastric epithelial AGS cells. METHODS: Cell viability was determined by MTT assay. IL-8 and CCL20 promoter activities were determined by a luciferease reporter gene assay. NF-κB-dependent transcriptional activity was determined by I-κBα degradation, NF-κB p65 nuclear translocation and a luciferase activity assay. IL-8 and CCL20 gene expression and protein secretion were determined by RT-PCR and an enzymelinked immunosorbent assay (ELISA). Total and phosphorylated forms of mitogen-activated protein kinases (MAPKs) were determined by Western blot. RESULTS: Treatment of AGS cells with DA-9601 reduced TNF-α-induced IL-8 and CCL20 promoter activities, as well as their gene expression and protein release. TNF-α also induced NF-κB-dependent transcriptional activity in AGS cells. In contrast, in cells treated with DA-9601, TNF-α-induced NF-κB activity was significantly blocked. Although all three MAP kinase family members were phosphorylated in response to TNF-α, a selective inhibitor of p38 kinase SB203580 only could inhibit both NF κB-dependent transcriptional activity and IL-8 and CCL20 production, suggesting a potential link between p38 kinase and NF-κB-dependent pathways in AGS cells. Interestingly, DA-9601 also selectively inhibited p38 kinase phosphorylation induced by TNF-α.CONCLUSION: DA-9601 blocked TNF-α-mediated inflammatory signals by potentially modulating the p38 kinase pathway and/or a signal leading to NF-κB dependent pathways in gastric epithelial cells.

  4. Kinetics of the gas-phase reactions of chlorine atoms with CH2F2, CH3CCl3 and CF3CFH2 over the temperature range 253 – 551 K

    DEFF Research Database (Denmark)

    Nilsson, Elna Johanna Kristina; Johnson, Matthew Stanley; Nielsen, Ole John;

    2009-01-01

    Relative rate techniques were used to study the title reactions in 930–1200 mbar of N2 diluent. The reaction rate coefficients measured in the present work are summarized by the expressions k(Cl+CH2F2) = 1.19×10-17 T 2 exp(-1023/T ) cm3 molecule-1 s-1 (253– 553 K), k(Cl+CH3CCl3) = 2.41×10-12 exp(...

  5. Rainbow trout CK9, a CCL25-like ancient chemokine that attracts and regulates B cells and macrophages, the main antigen presenting cells in fish

    Science.gov (United States)

    Aquilino, Carolina; Granja, Aitor G.; Castro, Rosario; Wang, Tiehui; Abos, Beatriz; Parra, David; Secombes, Christopher J.; Tafalla, Carolina

    2016-01-01

    CK9 is a rainbow trout (Oncorhynchus mykiss) CC chemokine phylogenetically related to mammalian CCL25. Although CK9 is known to be transcriptionally regulated in response to inflammation particularly in mucosal tissues, its functionality has never been revealed. In the current work, we have demonstrated that CK9 is chemoattractant for antigen presenting cells (APCs) expressing major histocompatibility complex class II (MHC II) on the cell surface. Among these APCs, CK9 has a strong chemotactic capacity for both B cells (IgM+ and IgT+) and macrophages. Along with its chemotactic capacities, CK9 modulated the MHC II turnover of B lymphocytes and up-regulated the phagocytic capacity of both IgM+ cells and macrophages. Although CK9 had no lymphoproliferative effects, it increased the survival of IgT+ lymphocytes. Furthermore, we have established that the chemoattractant capacity of CK9 is strongly increased after pre-incubation of leukocytes with a T-independent antigen, whereas B cell receptor (BCR) cross-linking strongly abrogated their capacity to migrate to CK9, indicating that CK9 preferentially attracts B cells at the steady state or under BCR-independent stimulation. These results point to CK9 being a key regulator of B lymphocyte trafficking in rainbow trout, able to modulate innate functions of teleost B lymphocytes and macrophages. PMID:27003360

  6. Preparation of ThO2-UO3 sols with uranium contents of 0 approx 35 % for gelation into microspheres in CCl4-ammonia media

    International Nuclear Information System (INIS)

    The conditions for producing mixed ThO2-UO3 sols with 0 ∼ 40 % U by neutralizing nitrate solutions with ammonia solution under pH control are studied. With 0 ∼ 35 % U, good source sols for gelation in CCl4-ammonia media are obtained. Colloid fraction of U in producible stable sols is lower than that of Th. The former, moreover, decreases considerably with increase in U content while the latter does only a little; this results abrupt decrease in their colloid fraction of (Th + U) with increase in U content. Whether gelation behavior of such sols is good or not depends on fraction of 4.1 nm or larger colloids, and on U content. The minimum value of the colloid fractions resulting no gel-sphere failure also decreases with increase in U content. The gel-sphere failure is a crack for lower U content and a hole like a dimple or a navel for higher one. The difference is also discussed. (author)

  7. Application of a new statistical mechanical model for calculating Kirkwood factors in self associating liquid systems to alkanol + CCl4 mixtures.

    Science.gov (United States)

    Vasiltsova, Tatiana; Heintz, Andreas; Nadolny, Holger; Weingärtner, Hermann

    2009-04-14

    A recently developed statistical-mechanical model for calculating Kirkwood correlation factors g(K) in self associating liquids and liquid mixtures has been applied for the simultaneous description of g(K) derived from dielectric constant data, the molar enthalpy of mixing H, and the infrared absorbtion of monomeric alcoholic species as function of the composition in alkanol + CCl(4) mixtures. The alkanols are methanol, ethanol, propanol, butan-1-ol, pentan-1-ol, hexan-1-ol, octan-1-ol, sec-butanol, tert-butanol and pentan-3-ol. The majority of parameters involved in the theory are obtained by independent quantum mechanical ab initio calculations of molecular clusters consisting of up to four alcohol molecules. As a consequence only two parameters have to be adjusted freely to each binary system, a third parameter responsible for the non-specific intermolecular dispersion interaction has been adjusted within a limited range of possible values given by physical arguments. Excellent agreement between theory and experimental data for g(K), H and IR absorbance is obtained covering the whole range of concentration. The theory also rationalizes the temperature dependence of these properties without adjusting further parameters. The Kirkwood correlation factor g(K) turns out to be a sensitive response to peculiarities of the molecular structure of hydrogen-bonded systems in the condensed liquid state. PMID:19325973

  8. Altered thymocyte migration during experimental acute Trypanosoma cruzi infection: combined role of fibronectin and the chemokines CXCL12 and CCL4.

    Science.gov (United States)

    Mendes-da-Cruz, Daniella Arêas; Silva, João Santana; Cotta-de-Almeida, Vinícius; Savino, Wilson

    2006-06-01

    We previously showed migration disturbances in the thymus during experimental infection with Trypanosoma cruzi, the causative agent of Chagas disease. These changes were related to the enhanced expression of extracellular matrix ligands and receptors, leading to the escape of immature cells to the periphery. Here, we analyzed the expression and role of selected chemokines (CXCL12 and CCL4) and their receptors (CXCR4 and CCR5) in regulating thymocyte migration in conjunction with extracellular matrix during acute T. cruzi infection. We found increased chemokine deposition in the thymus of infected mice when compared to controls, accompanied by enhanced co-localization with fibronectin as well as up-regulated surface expression of CXCR4 and CCR5 in thymocytes. We also noticed altered thymocyte migration towards the chemokines analyzed. Such an enhancement was even more prominent when fibronectin was added as a haptotatic stimulus in combination with a given chemokine. Our findings suggest that thymocyte migration results from a combined action of chemokines and extracellular matrix (ECM), which can be altered during pathological conditions such as T. cruzi infection, and may be at the origin of the changes in the T cell repertoire seen in this pathological process.

  9. The Effects of Taoren-Honghua Herb Pair on Pathological Microvessel and Angiogenesis-Associated Signaling Pathway in Mice Model of CCl4-Induced Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Shengyan Xi

    2016-01-01

    Full Text Available Chronic liver disease is one of the most common diseases that threaten human health. Effective treatment is still lacking in western medicine. Semen Persicae (Taoren and Flos Carthami (Honghua are known to relieve acute hepatic injury and inflammation, improve microcirculation, and reduce tissue fiber. The aim of our study is to investigate the potential mechanisms of Taoren-Honghua Herb Pair (THHP in murine model of chronic liver disease caused by Carbon Tetrachloride (CCl4. Mice were randomly divided into seven groups: (1 blank, (2 model, (3 control (colchicine, 0.1 mg/kg, (4 THHP (5.53, 2.67, and 1.33 g/kg, and (5 Tao Hong Siwu Decoction (THSWD (8.50 g/kg. Histological change and microvessels density were examined by microscopy. Hepatic function, serum fibrosis related factors, and hepatic vascular endothelial growth factor (VEGF were measured with ELISA. VEGF, kinase insert domain-containing receptor (KDR, Flt-1, and Akt mRNA expression in hepatic tissue were determined with PCR. Tissues of Akt, pAkt, KDR, and Flt-1 were measured with western blotting. Data from this study showed that THHP improved hepatic function and restrained the hepatic inflammation and fibrosis. Its role in inhibiting pathological angiogenesis and hepatic fibrogenesis may be through affecting the angiogenesis-associated VEGF and its upstream and downstream signaling pathways.

  10. Possible atmospheric lifetimes and chemical reaction mechanisms for selected HCFCs, HFCs, CH3CCl3, and their degradation products against dissolution and/or degradation in seawater and cloudwater

    Science.gov (United States)

    Wine, P. H.; Chameides, W. L.

    1990-01-01

    For a wide variety of atmospheric species including CO2, HNO3, and SO2, dissolution in seawater or cloudwater followed by hydrolysis or chemical reaction represents a primary pathway for removal from the atmosphere. In order to determine if this mechanism can also remove significant amounts of atmospheric chlorofluorocarbons (HCFC's), fluorocarbons (HFC's), and their degradation products, an investigation was undertaken as part of the Alternative Fluorocarbons Environmental Acceptability Study (AFEAS). In this investigation, the rates at which CHCl2CF3 (HCFC-123), CCl2FCH3 (HCFC-141b), CClF2CH3 (HCFC-142b), CHClF2 (HCFC-22), CHClFCF3 (HCFC-124) CH2FCF3 (HFC-134a) CHF2CH3 (HFC-152a), CHF2CF3 (HFC-125), and CH3CCl3 can be dissolved in the oceans and in cloudwater were estimated from the species' thermodynamic and chemical properties using simple mathematical formulations to simulate the transfer of gases from the atmosphere to the ocean or cloudwater. The ability of cloudwater and rainwater to remove gas phase degradation products of these compounds was also considered as was the aqueous phase chemistry of the degradation products. The results of this investigation are described.

  11. PENGARUH PERLINDUNGAN EKSTRAK RIMPANG BANGLE (Zingiber cassumunar ROXB TERHADAP KERUSAKAN HATI TIKUS YANG DIINDUKSI CCI4 [Protective Effect of Bangle (Zingiber cassumunar ROXB Rhizome Extract on CCl4-Induced Liver Damage of Rats

    Directory of Open Access Journals (Sweden)

    Elmeizy Arafah1

    2004-12-01

    Full Text Available Zingiber cassumunar Roxb known as Bangle, has antioxidative and antiinflammatory activities. It has been used for medicinal purposes traditionally. The aim of this study was to investigate whether administration of Z. cassumunar extracts orally may prevent acute liver damage induced by carbontetrachloride (CCl4 in rats. The study was carried out on 5 groups of male Sprague-Dawley rats (n=5. Group 1 was given ethyl acetate fraction of Bangle rhizome extract (30 mg/kg bw (KS, group 2 was given dry juice of Bangle rhizome (30 mg/kg bw (SK, group 3 was given curcuminoid (30 mg/kg bw (KUR, group 4 as negative control (KN given 5% Tween 80 solution (10 ml/kg bw and Group 5 as control (K. Carbontetrachloride 0,1 ml/kg bw was given orally after 7 days to group KS, SK, KUR and KN. Rats were terminated 24 hours after CCl4-induction. Liver injury was evaluated by analyzed SGPT and SGOT activities from the serum and histopathologycal examination was conducted on the liver. The results clearly indicated that extracts of Z. cassumunar could reduced significantly the degree of liver damage induced by CCl4. It may be concluded that Z. cassumunar rhizome could be used as substance for hepatoprotector

  12. Photocatalytic transformations of CCl{sub 3}Br, CBr{sub 3}F, CHCl{sub 2}Br and CH{sub 2}BrCl in aerobic and anaerobic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Calza, P.; Minero, C.; Pelizzetti, E. [Dipartimento di Chimica Analitica, Universita di Torino, 10125 Torino (Italy); Hiskia, A.; Papaconstantinou, E. [Institute of Physical Chemistry, NCSR Demokritos, 15310 Athens (Greece)

    2001-01-01

    Phototransformations of halomethanes containing chlorine and bromine (CCl{sub 3}Br, CHCl{sub 2}Br, CH{sub 2}ClBr) or bromine and fluorine (CBr{sub 3}F) have been investigated under aerobic and anaerobic conditions both in homogeneous system and heterogeneous photocatalysis. For all of those compounds, the complete disappearance of the primary compound and the stoichiometric concentration of halides was achieved. Several halogenated intermediates and oxygenated compounds were identified, so that it was possible to predict the degradation pathways followed by such halomethanes. Whereas the reductive steps are predominant in the initial degradation of CCl{sub 3}Br and CBr{sub 3}F, the oxidative steps are predominant in the initial CH{sub 2}ClBr steps. The two pathways have comparable importance for CHCl{sub 2}Br degradation. Methanol, acting as a hole scavenger, strongly increases the rate of disappearance for CCl{sub 3}Br and CBr{sub 3}F.

  13. Distance and virtual laboratories

    NARCIS (Netherlands)

    Bauer, P.; Fedak, V.; Hajek, V.

    2007-01-01

    The paper deals with basic philosophy and structure of a remote controlled laboratory for experimentation in Electrical Engineering. The laboratory collects experiments from fields of Power Electronics, Electrical Machines, Electro-Mechanical and Motion Control Systems. The workbenches in the real l

  14. ELECTROPNEUMATIC AUTOMATION EDUCATIONAL LABORATORY

    OpenAIRE

    Dolgorukov, S. O.; National Aviation University; Roman, B. V.; National Aviation University

    2013-01-01

    The article reflects current situation in education regarding mechatronics learning difficulties. Com-plex of laboratory test benches on electropneumatic automation are considered as a tool in advancing through technical science. Course of laboratory works developed to meet the requirement of efficient and reliable way of practical skills acquisition is regarded the simplest way for students to learn the ba-sics of mechatronics.

  15. Biotechnology Laboratory Methods.

    Science.gov (United States)

    Davis, Robert H.; Kompala, Dhinakar S.

    1989-01-01

    Describes a course entitled "Biotechnology Laboratory" which introduces a variety of laboratory methods associated with biotechnology. Describes the history, content, and seven experiments of the course. The seven experiments are selected from microbiology and molecular biology, kinetics and fermentation, and downstream processing-bioseparations.…

  16. The Virtual Robotics Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Kress, R.L.; Love, L.J.

    1999-09-01

    The growth of the Internet has provided a unique opportunity to expand research collaborations between industry, universities, and the national laboratories. The Virtual Robotics Laboratory (VRL) is an innovative program at Oak Ridge National Laboratory (ORNL) that is focusing on the issues related to collaborative research through controlled access of laboratory equipment using the World Wide Web. The VRL will provide different levels of access to selected ORNL laboratory secondary education programs. In the past, the ORNL Robotics and Process Systems Division has developed state-of-the-art robotic systems for the Army, NASA, Department of Energy, Department of Defense, as well as many other clients. After proof of concept, many of these systems sit dormant in the laboratories. This is not out of completion of all possible research topics. but from completion of contracts and generation of new programs. In the past, a number of visiting professors have used this equipment for their own research. However, this requires that the professor, and possibly his/her students, spend extended periods at the laboratory facility. In addition, only a very exclusive group of faculty can gain access to the laboratory and hardware. The VRL is a tool that enables extended collaborative efforts without regard to geographic limitations.

  17. The Virtual Robotics Laboratory

    International Nuclear Information System (INIS)

    The growth of the Internet has provided a unique opportunity to expand research collaborations between industry, universities, and the national laboratories. The Virtual Robotics Laboratory (VRL) is an innovative program at Oak Ridge National Laboratory (ORNL) that is focusing on the issues related to collaborative research through controlled access of laboratory equipment using the World Wide Web. The VRL will provide different levels of access to selected ORNL laboratory equipment to outside universities, industrial researchers, and elementary and secondary education programs. In the past, the ORNL Robotics and Process Systems Division (RPSD) has developed state-of-the-art robotic systems for the Army, NASA, Department of Energy, Department of Defense, as well as many other clients. After proof of concept, many of these systems sit dormant in the laboratories. This is not out of completion of all possible research topics, but from completion of contracts and generation of new programs. In the past, a number of visiting professors have used this equipment for their own research. However, this requires that the professor, and possibly his students, spend extended periods at the laboratory facility. In addition, only a very exclusive group of faculty can gain access to the laboratory and hardware. The VRL is a tool that enables extended collaborative efforts without regard to geographic limitations

  18. NVLAP calibration laboratory program

    Energy Technology Data Exchange (ETDEWEB)

    Cigler, J.L.

    1993-12-31

    This paper presents an overview of the progress up to April 1993 in the development of the Calibration Laboratories Accreditation Program within the framework of the National Voluntary Laboratory Accreditation Program (NVLAP) at the National Institute of Standards and Technology (NIST).

  19. Quality in Teaching Laboratories.

    Science.gov (United States)

    Stubington, John F.

    1995-01-01

    Describes a Japanese process-oriented approach called KAIZEN for improving the quality of existing teaching laboratories. It provides relevant quality measurements and indicates how quality can be improved. Use of process criteria sidesteps the difficulty of defining quality for laboratory experiments and allows separation of student assessment…

  20. [Accreditation of medical laboratories].

    Science.gov (United States)

    Horváth, Andrea Rita; Ring, Rózsa; Fehér, Miklós; Mikó, Tivadar

    2003-07-27

    In Hungary, the National Accreditation Body was established by government in 1995 as an independent, non-profit organization, and has exclusive rights to accredit, amongst others, medical laboratories. The National Accreditation Body has two Specialist Advisory Committees in the health care sector. One is the Health Care Specialist Advisory Committee that accredits certifying bodies, which deal with certification of hospitals. The other Specialist Advisory Committee for Medical Laboratories is directly involved in accrediting medical laboratory services of health care institutions. The Specialist Advisory Committee for Medical Laboratories is a multidisciplinary peer review group of experts from all disciplines of in vitro diagnostics, i.e. laboratory medicine, microbiology, histopathology and blood banking. At present, the only published International Standard applicable to laboratories is ISO/IEC 17025:1999. Work has been in progress on the official approval of the new ISO 15189 standard, specific to medical laboratories. Until the official approval of the International Standard ISO 15189, as accreditation standard, the Hungarian National Accreditation Body has decided to progress with accreditation by formulating explanatory notes to the ISO/IEC 17025:1999 document, using ISO/FDIS 15189:2000, the European EC4 criteria and CPA (UK) Ltd accreditation standards as guidelines. This harmonized guideline provides 'explanations' that facilitate the application of ISO/IEC 17025:1999 to medical laboratories, and can be used as a checklist for the verification of compliance during the onsite assessment of the laboratory. The harmonized guideline adapted the process model of ISO 9001:2000 to rearrange the main clauses of ISO/IEC 17025:1999. This rearrangement does not only make the guideline compliant with ISO 9001:2000 but also improves understanding for those working in medical laboratories, and facilitates the training and education of laboratory staff. With the