WorldWideScience

Sample records for mdi factors derived

  1. Development of the Muscle Dysmorphia Inventory (MDI).

    Science.gov (United States)

    Rhea, D J; Lantz, C D; Cornelius, A E

    2004-12-01

    The development of the 6-factor, 27-item Muscle Dysmorphia Inventory (MDI) was based on Lantz et al. proposed model of characteristics associated with Muscle Dysmorphia. quantitative procedures including item-to-total correlations, exploratory and confirmatory factor analyses, and structure equation modeling confirmed the construct validity of the scale. Convergent validity was also tested. bodybuilding and powerlifting competition venues, weight training facilities, and university athletic venues. the 1(st) study consisted of 77 experienced male free weight lifters. The 2(nd) study consisted of 156 male non-competitive bodybuilders and weight lifters and 168 elite level powerlifters and bodybuilders. The 3(rd) study consisted of 151 male and female bodybuilders and weight lifters. each participant completed demographic information, the MDI, Drive for Thinness subscale of the Eating Disorder Inventory, and the Training Dependency subscale of the Bodybuilding Dependence Scale. Reliability estimates (Cronbach's a) ranged from 0.72 to 0.94. Factor loadings in all 3 studies supported the 6-factor structure (size/symmetry, supplement use, exercise dependence, pharmacological use, dietary behavior, and physique protection). Much of the scale validation was focused on construct validity, however, correlations with the MDI's subscales and the Training Dependency subscale of the Bodybuilding Dependence Scale and the Drive for Thinness subscale of the Eating Disorder Inventory provided evidence of convergent validity also. From these preliminary results, the MDI appears to contribute to the identification of a newly formed disorder by offering a multi-dimensional measure of factors related to Muscle Dysmorphia.

  2. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  3. The mitochondrial outer membrane protein MDI promotes local protein synthesis and mtDNA replication.

    Science.gov (United States)

    Zhang, Yi; Chen, Yong; Gucek, Marjan; Xu, Hong

    2016-05-17

    Early embryonic development features rapid nuclear DNA replication cycles, but lacks mtDNA replication. To meet the high-energy demands of embryogenesis, mature oocytes are furnished with vast amounts of mitochondria and mtDNA However, the cellular machinery driving massive mtDNA replication in ovaries remains unknown. Here, we describe a Drosophila AKAP protein, MDI that recruits a translation stimulator, La-related protein (Larp), to the mitochondrial outer membrane in ovaries. The MDI-Larp complex promotes the synthesis of a subset of nuclear-encoded mitochondrial proteins by cytosolic ribosomes on the mitochondrial surface. MDI-Larp's targets include mtDNA replication factors, mitochondrial ribosomal proteins, and electron-transport chain subunits. Lack of MDI abolishes mtDNA replication in ovaries, which leads to mtDNA deficiency in mature eggs. Targeting Larp to the mitochondrial outer membrane independently of MDI restores local protein synthesis and rescues the phenotypes of mdi mutant flies. Our work suggests that a selective translational boost by the MDI-Larp complex on the outer mitochondrial membrane might be essential for mtDNA replication and mitochondrial biogenesis during oogenesis. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  4. MDI: Mathematica database interface for the MFEDB

    International Nuclear Information System (INIS)

    Wiley, J.C.; Miner, W.H. Jr.; Ross, D.W.

    1992-04-01

    We describe a new interface for the Magnetic Fusion Energy Database, MFEDB, which uses Mathematica reg-sign as a front end. MDI is a Mathematica package that defines a basic set of MFEDB access functions. The package will also accept standard SQL queries. Each function returns Mathematica-style lists, which can then be manipulated with any of the Mathematica functions. MDI also provides some utility functions for plotting and analyzing the data. The MDI package essentially makes the MFEDB an extension of Mathematica. The user may use any of the many Mathematica front-ends including telnet, X-Windows, or a notebook. The mdi.m package may be obtained by anonymous FTP from the MFEDB site or by use of netmfe, and E-mail database interface. MDI is a example of distributed computing. Behind the user interface, MDI calls an RPC client program that communicates with an RPC server on the MFEDB computer. It relies on the network communication capabilities of Mathematica to connect the user to a workstation running the Mathematica kernel. The Mathematica kernel is then connected to the MFEDB host workstation by a client/server pair of RPC processes. If the Mathematica kernel is to be run on the users' machine, the RPC client program must also be obtained and installed. The MDI RPC server is also available for users who would like to provide their own client software. The server returns ASCII tables from standards queries and may be accessed and processed by any program on the internet that has access to RPC services

  5. Reliability of the MDi Psoriasis® Application to Aid Therapeutic Decision-Making in Psoriasis.

    Science.gov (United States)

    Moreno-Ramírez, D; Herrerías-Esteban, J M; Ojeda-Vila, T; Carrascosa, J M; Carretero, G; de la Cueva, P; Ferrándiz, C; Galán, M; Rivera, R; Rodríguez-Fernández, L; Ruiz-Villaverde, R; Ferrándiz, L

    2017-09-01

    Therapeutic decisions in psoriasis are influenced by disease factors (e.g., severity or location), comorbidity, and demographic and clinical features. We aimed to assess the reliability of a mobile telephone application (MDi-Psoriasis) designed to help the dermatologist make decisions on how to treat patients with moderate to severe psoriasis. We analyzed interobserver agreement between the advice given by an expert panel and the recommendations of the MDi-Psoriasis application in 10 complex cases of moderate to severe psoriasis. The experts were asked their opinion on which treatments were most appropriate, possible, or inappropriate. Data from the same 10 cases were entered into the MDi-Psoriasis application. Agreement was analyzed in 3 ways: paired interobserver concordance (Cohen's κ), multiple interobserver concordance (Fleiss's κ), and percent agreement between recommendations. The mean percent agreement between the total of 1210 observations was 51.3% (95% CI, 48.5-54.1%). Cohen's κ statistic was 0.29 and Fleiss's κ was 0.28. Mean agreement between pairs of human observers only, excluding the MDi-Psoriasis recommendations, was 50.5% (95% CI, 47.6-53.5%). Paired agreement between the recommendations of the MDi-Psoriasis tool and the majority opinion of the expert panel (Cohen's κ) was 0.44 (68.2% agreement). The MDi-Psoriasis tool can generate recommendations that are comparable to those of experts in psoriasis. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. An OOP Approach to Simplify MDI Application Development An OOP Approach to Simplify MDI Application Development

    Directory of Open Access Journals (Sweden)

    Donato Hernández Fusilier

    2012-02-01

    Full Text Available The Multiple Document Interface (MDI is a Microsoft Windows specification that allows managing multiple documents using a single graphic interface application. An MDI application allows opening several documents simultaneously. Only one document is active at a particular time. MDI applications can be deployed using Win32 or Microsoft Foundation Classes (MFC. Programs developed using Win32 are faster than those using MFC. However, Win32applications are difficult to implement and prone to errors. It should be mentioned that, learning how to properly use MFC to deploy MDI applications is not simple, and performance is typically worse than that of Win32 applications. A method to simplify the development of MDI applications using Object-Oriented Programming (OOP is proposed. Subsequently, it is shown that this method generates compact code that is easier to read and maintain than other methods (i.e., MFC. Finally, it is demonstrated that the proposed method allowsthe rapid development of MDI applications without sacrificing application performance.La Interfase para Múltiples Documentos (MDI es una especificación del sistema operativo Microsoft Windows que permite manipular varios documentos usando un sólo programa. Un programa del tipo MDI permite abrir varios documentos simultáneamente. En un instante dado, sólo un documento es activo. Los programas del tipo MDI pueden desarrollarseu sando Win32 o las clases fundamentales de Microsoft (MFC. Los programas desarrollados usando Win32 son más rápidos que los programas que usan MFC. Sin embargo, éstos son difíciles de implementar promoviendo la existencia de errores. Cabe mencionar que el desarrollo de programas del tipo MDI usando MFC no es sencillo, y que su desempeño estípicamente peor que el de un programa del tipo Win32. Se propone un método que drásticamente simplifica el desarrollo de programas del tipo MDI por medio de la Programación Orientada a Objetos (POO. Se demuestra que el m

  7. Barriers and supports to implementation of MDI/spacer use in nine Canadian pediatric emergency departments: a qualitative study

    Directory of Open Access Journals (Sweden)

    Graham Ian D

    2009-10-01

    Full Text Available Abstract Background Despite recent research supporting the use of metered dose inhalers with spacer devices (MDI/spacers in pediatric emergency departments (PEDs for acute exacerbations of asthma, uptake of this practice has been slow. The objectives of this study were to determine the barriers and supports to implementing MDI/spacer research and to identify factors associated with early and late adoption of MDI/spacers in Canadian PEDs. Methods Using a comparative case study design, we classified nine tertiary care pediatric hospital PEDs based on their stage of implementation. Data were collected using focus group interviews with physicians, registered nurses (RNs, and respiratory therapists (RTs, and individual interviews with both patient care and medical directors at each site. Initial coding was based on the Ottawa Model of Research Use (OMRU categories of elements known to influence the uptake of innovations. Results One hundred and fifty healthcare professionals from nine different healthcare institutions participated in this study. Lack of leadership in the form of a research champion, a lack of consensus about the benefits of MDI/spacers among staff, perceived resistance from patients/parents, and perceived increased cost and workload associated with MDI/spacer use were the most prevalent barriers to the adoption of the MDI/spacer. Common strategies used by early-adopting sites included the active participation of all professional groups in the adoption process in addition to a well-planned and executed educational component for staff, patients, and families. Early adopter sites were also more likely to have the MDI/spacer included in a clinical protocol/pathway. Conclusion Potential barriers and supports to implementation have been identified that will help EDs adopt MDI/spacer use. Future interventions intended to increase MDI/spacer use in PEDs will need to be sensitive to the barriers identified in this study.

  8. Risk Factors in Derivatives Markets

    Directory of Open Access Journals (Sweden)

    Raimonda Martinkutė-Kaulienė

    2015-02-01

    Full Text Available The objective of the article is to analyse and present the classification of risks actual to derivative securities. The analysis is based on classical and modern literature findings and analysis of newest statistical data. The analysis led to the conclusion, that the main risks typical for derivatives contracts and their traders are market risk, liquidity risk, credit and counterparty risk, legal risk and transactions risk. Pricing risk and systemic risk is also quite important. The analysis showed that market risk is the most important kind of risk that in many situations influences the level of remaining risks.

  9. Derivation of Batho's correction factor for heterogeneities

    International Nuclear Information System (INIS)

    Lulu, B.A.; Bjaerngard, B.E.

    1982-01-01

    Batho's correction factor for dose in a heterogeneous, layered medium is derived from the tissue--air ratio method (TARM). The reason why the Batho factor is superior to the TARM factor at low energy is ascribed to the fact that it accounts for the distribution of the scatter-generating matter along the centerline. The poor behavior of the Batho factor at high energies is explained as a consequence of the lack of electron equilibrium at appreciable depth below the surface. Key words: Batho factor, heterogeneity, inhomogeneity, tissue--air ratio method

  10. Sustainable Intensified Process Retrofit for the Production of MDI

    DEFF Research Database (Denmark)

    Babi, Deenesh Kavi; Woodley, John; Gani, Rafiqul

    Process intensification (PI) is a means by which processes can be made more efficient and sustainable at different levels, the unit operations, functional and phenomena levels. Therefore PI can be used for making process improvements at the functional level for the production of an important poly...... polyurethane, methylene diphenyldi-isocyanate (MDI)....

  11. The Brain Derived Neurotrophic Factor and Personality

    OpenAIRE

    Christian Montag

    2014-01-01

    The study of the biological basis of personality is a timely research endeavor, with the aim of deepening our understanding of human nature. In recent years, a growing body of research has investigated the role of the brain derived neurotrophic factor (BDNF) in the context of individual differences across human beings, with a focus on personality traits. A large number of different approaches have been chosen to illuminate the role of BDNF for personality, ranging from the measurement of BDNF...

  12. Measurements of brain-derived neurotrophic factor

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Klein, Anders Bue; Vinberg, Maj

    2007-01-01

    Although numerous studies have dealt with changes in blood brain-derived neurotrophic factor (BDNF), methodological issues about BDNF measurements have only been incompletely resolved. We validated BDNF ELISA with respect to accuracy, reproducibility and the effect of storage and repeated freezing...... (18.6+/-1.3 ng/ml versus 16.5+/-1.4 ng/ml), and showed a right-skewed BDNF concentration distribution. No association between whole blood BDNF concentrations and thrombocyte count, age, or BDNF genotype was found. In conclusion, the BDNF ELISA assay determines whole blood BDNF accurately and with high...

  13. Derivation of dose conversion factors for tritium

    Energy Technology Data Exchange (ETDEWEB)

    Killough, G. G.

    1982-03-01

    For a given intake mode (ingestion, inhalation, absorption through the skin), a dose conversion factor (DCF) is the committed dose equivalent to a specified organ of an individual per unit intake of a radionuclide. One also may consider the effective dose commitment per unit intake, which is a weighted average of organ-specific DCFs, with weights proportional to risks associated with stochastic radiation-induced fatal health effects, as defined by Publication 26 of the International Commission on Radiological Protection (ICRP). This report derives and tabulates organ-specific dose conversion factors and the effective dose commitment per unit intake of tritium. These factors are based on a steady-state model of hydrogen in the tissues of ICRP's Reference Man (ICRP Publication 23) and equilibrium of specific activities between body water and other tissues. The results differ by 27 to 33% from the estimate on which ICRP Publication 30 recommendations are based. The report also examines a dynamic model of tritium retention in body water, mineral bone, and two compartments representing organically-bound hydrogen. This model is compared with data from human subjects who were observed for extended periods. The manner of combining the dose conversion factors with measured or model-predicted levels of contamination in man's exposure media (air, drinking water, soil moisture) to estimate dose rate to an individual is briefly discussed.

  14. Derivation of dose conversion factors for tritium

    International Nuclear Information System (INIS)

    Killough, G.G.

    1982-03-01

    For a given intake mode (ingestion, inhalation, absorption through the skin), a dose conversion factor (DCF) is the committed dose equivalent to a specified organ of an individual per unit intake of a radionuclide. One also may consider the effective dose commitment per unit intake, which is a weighted average of organ-specific DCFs, with weights proportional to risks associated with stochastic radiation-induced fatal health effects, as defined by Publication 26 of the International Commission on Radiological Protection (ICRP). This report derives and tabulates organ-specific dose conversion factors and the effective dose commitment per unit intake of tritium. These factors are based on a steady-state model of hydrogen in the tissues of ICRP's Reference Man (ICRP Publication 23) and equilibrium of specific activities between body water and other tissues. The results differ by 27 to 33% from the estimate on which ICRP Publication 30 recommendations are based. The report also examines a dynamic model of tritium retention in body water, mineral bone, and two compartments representing organically-bound hydrogen. This model is compared with data from human subjects who were observed for extended periods. The manner of combining the dose conversion factors with measured or model-predicted levels of contamination in man's exposure media (air, drinking water, soil moisture) to estimate dose rate to an individual is briefly discussed

  15. Influences of the Ratio of Polyol and MDI on the Acoustic Parameters of Polyurethane

    Science.gov (United States)

    Wang, Yonghua; Liu, Zheming; Wu, Haiquan; Zhang, Chengchun; Yu, Huadong; Ren, Luquan; Ichchou, Mohamed

    2018-05-01

    In this paper, the influence of different ratio of polyol and MDI on the absorption coefficient and acoustic parameters of polyurethane was studied. Ratio of 100:40 and 100:45 show the best sound absorption performance, and the change trend of transmission loss and sound absorption coefficient are opposite. The flow resistance increased with the increasing of the ratio of polyol and MDI, the greater the flow resistance, the worse the high frequency sound absorption property of the polyurethane. When the ratio of polyol and MDI keep 100:45, the minimum porosity of sample, the polyurethane porosity increase with the ratio of polyol and MDI increase.

  16. CONCEPTS, MODELS AND IMPLEMENTATION OF THE MARINE SPATIAL DATA INFRASTRUCTURE IN GERMANY (MDI-DE

    Directory of Open Access Journals (Sweden)

    C. Rüh

    2012-07-01

    Full Text Available In Germany currently the development of a marine data infrastructure takes place with the aim of merging information concerning the fields coastal engineering, hydrography and surveying, protection of the marine environment, maritime conservation, regional planning and coastal research. This undertaking is embedded in a series of regulations and developments on many administrative levels from which specifications and courses of action derive. To set up a conceptual framework for the marine data infrastructure (MDI-DE scientists at the Professorship for Geodesy and Geoinformatics at Rostock University are building a reference model, evaluating meta-information systems and developing models to support common workflows in marine applications. The reference model for the marine spatial data infrastructure of Germany (MDI-DE is the guideline for all developments inside this infrastructure. Because the undertaking is embedded in a series of regulations and developments this paper illustrates an approach on modelling a scenario for the Marine Strategy Framework Directive (MSFD using the Unified Modelling Language (UML. Evaluating how other countries built their marine spatial infrastructures is of main importance, to learn where obstacles are and errors are likely to occur. To be able to look at other initiatives from a neutral point of view it is necessary to construct a framework for evaluation of marine spatial data infrastructures. Spatial data infrastructure assessment approaches were used as bases and were expanded to meet the requirements of the marine domain. As an international case-study this paper will look at Canada's Marine Geospatial Data Infrastructure (MGDI, COINAtlantic and GeoPortal.

  17. Concepts, Models and Implementation of the Marine Spatial Data Infrastructure in Germany Mdi-De

    Science.gov (United States)

    Rüh, C.; Bill, R.

    2012-07-01

    In Germany currently the development of a marine data infrastructure takes place with the aim of merging information concerning the fields coastal engineering, hydrography and surveying, protection of the marine environment, maritime conservation, regional planning and coastal research. This undertaking is embedded in a series of regulations and developments on many administrative levels from which specifications and courses of action derive. To set up a conceptual framework for the marine data infrastructure (MDI-DE) scientists at the Professorship for Geodesy and Geoinformatics at Rostock University are building a reference model, evaluating meta-information systems and developing models to support common workflows in marine applications. The reference model for the marine spatial data infrastructure of Germany (MDI-DE) is the guideline for all developments inside this infrastructure. Because the undertaking is embedded in a series of regulations and developments this paper illustrates an approach on modelling a scenario for the Marine Strategy Framework Directive (MSFD) using the Unified Modelling Language (UML). Evaluating how other countries built their marine spatial infrastructures is of main importance, to learn where obstacles are and errors are likely to occur. To be able to look at other initiatives from a neutral point of view it is necessary to construct a framework for evaluation of marine spatial data infrastructures. Spatial data infrastructure assessment approaches were used as bases and were expanded to meet the requirements of the marine domain. As an international case-study this paper will look at Canada's Marine Geospatial Data Infrastructure (MGDI), COINAtlantic and GeoPortal.

  18. Design optimization of a novel pMDI actuator for systemic drug delivery.

    Science.gov (United States)

    Kakade, Prashant P; Versteeg, Henk K; Hargrave, Graham K; Genova, Perry; Williams Iii, Robert C; Deaton, Daniel

    2007-01-01

    Pressurized metered dose inhalers (pMDIs) are the most widely prescribed and economical respiratory drug delivery systems. Conventional pMDI actuators-those based on "two-orifice-and-sump" designs-produce an aerosol with a reasonable respirable fraction, but with high aerosol velocity. The latter is responsible for high oropharyngeal deposition, and consequently low drug delivery efficiency. Kos' pMDI technology is based on a proprietary vortex nozzle actuator (VNA), an innovative actuator configuration that seeks to reduce aerosol plume velocity, thereby promoting deep lung deposition. Using VNA development as a case study, this paper presents a systematic design optimization process to improve the actuator performance through use of advanced optical characterization tools. The optimization effort mainly relied on laser-based optical diagnostics to provide an improved understanding of the fundamentals of aerosol formation and interplay of various geometrical factors. The performance of the optimized VNA design thus evolved was characterized using phase Doppler anemometry and cascade impaction. The aerosol velocities for both standard and optimized VNA designs were found to be comparable, with both notably less than conventional actuators. The optimized VNA design also significantly reduces drug deposition in the actuator as well as USP throat adapter, which in turn, leads to a significantly higher fine particle fraction than the standard design (78 +/- 3% vs. 63 +/- 2% on an ex valve basis). This improved drug delivery efficiency makes VNA technology a practical proposition as a systemic drug delivery platform. Thus, this paper demonstrates how advanced optical diagnostic and characterization tools can be used in the development of high efficiency aerosol drug delivery devices.

  19. Solar Polar Field Observed by SOHO/MDI and Hinode

    Science.gov (United States)

    Liu, Y.

    2009-12-01

    Using 1-minute cadence time-series full disk magnetograms taken by SOHO/MDI in 2007 March, and the corresponding Hinode/SOT vector magnetograms, I have studied evolutionary characteristics of magnetic elements in Sun's south polar region in solar minimum. It is found that the lifetime of magnetic elements is 17.0 hours on average with an average lifetime of 21.8 hours for elements with positive field, the dominant polarity in the south pole, and 1.6 hours for elements with negative field. The elements with positive field are dominant in the south pole with a percentage of 76% in element number and 90.5% in magnetic flux. The lifetime and magnetic flux of the elements is found to be highly related. This agrees with some previous studies for the elements in low latitude quiet regions. Using an image cross correlation method, I also measure solar rotation rate at high latitude, up to 85° in latitude, which is ω = 2.914-0.342 × sin2φ-0.482×sin4φ μrad/s sidereal. It agrees with previous studies using spectroscopic and image cross correlation methods, and also agrees with the results from some work using the element tracking method in which the sample of tracked elements is large. The consistency of those results from different data and methods strongly suggests that this rate at high latitude is reliable.

  20. Association assessment of platelet derived growth factor B gene ...

    African Journals Online (AJOL)

    Background: Coronary artery disease (CAD) is the most frequent cause of morbidity and mortality in the world and it is known as a multifactorial disorder which is influenced by both genetic and environmental factors. Based on different assays, the platelet derived growth factor B (PDGF-B) gene is shown to be amongst the ...

  1. Determinants of serum brain-derived neurotrophic factor

    NARCIS (Netherlands)

    Bus, B. A. A.; Molendijk, M. L.; Penninx, B. J. W. H.; Buitelaar, J. K.; Kenis, G.; Prickaerts, J.; Elzinga, B. M.; Voshaar, R. C. Oude

    Background: Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of growth factors and affects the survival and plasticity of neurons in the adult central nervous system. The high correlation between cortical and serum BDNF levels has led to many human studies on BDNF levels

  2. Microphase separation behavior on the surfaces of PEG-MDI-PDMS multiblock copolymer coatings

    International Nuclear Information System (INIS)

    Fang Hongxia; Zhou Shuxue; Wu Limin

    2006-01-01

    A series of poly(ethylene glycol)(PEG)-4,4'-diphenylmethanediisocyanate(MDI)-poly(dimethylsiloxane) (PDMS) multiblock copolymers were synthesized by employing two-step growth polymerization technique. Atomic force microscopy (AFM) observed nanoscopically well-organized phase-separated surfaces consisting of hydrophilic domain from PEG and MDI segments and hydrophobic domain from PDMS segments even with 50 wt.% PDMS in the copolymer, and the multiblock copolymer coatings presented a surface free energy of as low as 6-8 mN m -1

  3. Stromal cell-derived factor 1α (SDF-1α)

    DEFF Research Database (Denmark)

    Li, Dana; Bjørnager, Louise; Langkilde, Anne

    2016-01-01

    OBJECTIVES: Stromal cell-derived factor 1a (SDF-1α), is a chemokine and is able to home hematopoietic progenitor cells to injured areas of heart tissue for structural repair. Previous studies have found increased levels of SDF-1α in several cardiac diseases, but only few studies have investigated...

  4. Brain-derived neurotrophic factor and early-life stress

    Indian Academy of Sciences (India)

    2016-10-24

    Oct 24, 2016 ... The brain-derived neurotrophic factor (BDNF) is a key regulator of neural development and ... forms are produced by splicing individual non-coding ..... VII and. IX m. RNA. ↑. mBDNF. ↓. (MS). 5. BDNF expression was unch;.

  5. A comparison of the major depression inventory (MDI) and the beck depression inventory (BDI) in severely depressed patients

    DEFF Research Database (Denmark)

    Konstantinidis, Anastasios; Martiny, Klaus; Bech, Per

    2011-01-01

    We set out to examine the psychometric properties of the MDI in comparison to the BDI in a mixed group of patients with primary depression.......We set out to examine the psychometric properties of the MDI in comparison to the BDI in a mixed group of patients with primary depression....

  6. Analytically derived weighting factors for transmission tomography cone beam projections

    International Nuclear Information System (INIS)

    Yao Weiguang; Leszczynski, Konrad

    2009-01-01

    Weighting factors, which define the contributions of individual voxels of a 3D object to individual projection elements (pixels) on the detector, are the basic elements required in iterative tomographic reconstructions from transmission projections. Exact or as accurate as possible values for weighting factors are required in high-resolution reconstructions. Geometric complexity of the problem, however, makes it difficult to obtain exact weighting factor values. In this work, we derive an analytical expression for the weighting factors in cone beam projection geometry. The resulting formula is validated and applied to reconstruction from mega and kilovoltage x-ray cone beam projections. The reconstruction speed and accuracy are significantly improved by using the weighting factor values.

  7. Evaluation of workers' exposure to methylene diphenyl diisocyanate (MDI) in an automobile manufacturing company, Iran.

    Science.gov (United States)

    Kakooei, Hossein; Shahtaheri, Seyed Jamaleddin; Karbasi, Hossein-Ali

    2006-01-01

    Evaluation of personal inhalation exposure to methylene diphenyl diisocyanate (MDI) among 39 employees, working in the window fixation and window glue processes in an automobile manufacturing company was performed. This study was conducted for both case and control groups. After sampling and sample preparation processes, MDI was determined with a UV-VIS spectrophotometer at 590 nm; the lung function was assessed with a digital spirometer, too. The average concentration of MDI in the window fixation, and window glue workplaces were 34.53 and 27.37 micro g/m3, respectively, which was lower than the threshold limit value (TLV) recommended by the American Conference of Governmental Industrial Hygienists (ACGIH) (51 micro g/m3). Respiratory symptoms in the exposed group were significantly different compared to the unexposed group (p < .05). Lung capacities in the case group were lower than in the control group (p < .05). Therefore, MDI can be easily measured making it possible to evaluate the adverse effects caused by occupational exposure.

  8. Purification of human platelet-derived growth factor

    International Nuclear Information System (INIS)

    Raines, E.W.; Ross, R.

    1985-01-01

    The paper describes a method for purification of human platelet-derived growth factor (PDGF) from outdated platelet-rich plasma (PRP) using commonly available laboratory reagents and yielding a mitogen purified 800,000-fold over the starting material. [ 3 H]thymidine incorporation into DNA of cultured cells responsive to PDGF represents the most readily available method to follow its purification and define the biological activity of a purified preparation. Other assays to quantitate PDGF include radioreceptor assay and radioimmunoassay

  9. Time-Series Analyses of Supergranule Characteristics Compared Between SDO/HMI, SOHO/MDI and Simulated Datasets

    Science.gov (United States)

    Williams, Peter E.; Pesnell, William Dean

    2012-01-01

    Supergranulation is a well-observed solar phenomenon despite its underlying mechanisms remaining a mystery. Originally considered to arise due to convective motions, alternative mechanisms have been suggested such as the cumulative downdrafts of granules as well as displaying wave-like properties. Supergranule characteristics are well documented, however. Supergranule cells are approximately 35 Mm across, have lifetimes on the order of a day and have divergent horizontal velocities of around 300 mis, a factor of 10 higher than their central radial components. While they have been observed using Doppler methods for more than half a century, their existence is also observed in other datasets such as magneto grams and Ca II K images. These datasets clearly show the influence of supergranulation on solar magnetism and how the local field is organized by the flows of supergranule cells. The Heliospheric and Magnetic Imager (HMI) aboard the Solar Dynamics Observatory (SDO) continues to produce Doppler images enabling the continuation of supergranulation studies made with SOHO/MDI, but with superior temporal and spatial resolution. The size-distribution of divergent cellular flows observed on the photosphere now reaches down to granular scales, allowing contemporaneous comparisons between the two flow components. SOHO/MDI Doppler observations made during the minima of cycles 22/23 and 23/24 exhibit fluctuations of supergranule characteristics (global averages of the supergranule size, size-range and horizontal velocity) with periods of 3-5 days. Similar fluctuations have been observed in SDO/HMI Dopplergrams and the high correlation between co-temporal HMI & MOl suggest a solar origin. Their nature has been probed by invoking data simulations that produce realistic Dopplergrams based on MOl data.

  10. Derivation of Sky-View Factors from LIDAR Data

    Science.gov (United States)

    Kidd, Christopher; Chapman, Lee

    2013-01-01

    The use of Lidar (Light Detection and Ranging), an active light-emitting instrument, is becoming increasingly common for a range of potential applications. Its ability to provide fine resolution spatial and vertical resolution elevation data makes it ideal for a wide range of studies. This paper demonstrates the capability of Lidar data to measure sky view factors (SVF). The Lidar data is used to generate a spatial map of SVFs which are then compared against photographically-derived SVF at selected point locations. At each location three near-surface elevations measurements were taken and compared with collocated Lidar-derived estimated. It was found that there was generally good agreement between the two methodologies, although with decreasing SVF the Lidar-derived technique tended to overestimate the SVF: this can be attributed in part to the spatial resolution of the Lidar sampling. Nevertheless, airborne Lidar systems can map sky view factors over a large area easily, improving the utility of such data in atmospheric and meteorological models.

  11. Multi-factor energy price models and exotic derivatives pricing

    Science.gov (United States)

    Hikspoors, Samuel

    The high pace at which many of the world's energy markets have gradually been opened to competition have generated a significant amount of new financial activity. Both academicians and practitioners alike recently started to develop the tools of energy derivatives pricing/hedging as a quantitative topic of its own. The energy contract structures as well as their underlying asset properties set the energy risk management industry apart from its more standard equity and fixed income counterparts. This thesis naturally contributes to these broad market developments in participating to the advances of the mathematical tools aiming at a better theory of energy contingent claim pricing/hedging. We propose many realistic two-factor and three-factor models for spot and forward price processes that generalize some well known and standard modeling assumptions. We develop the associated pricing methodologies and propose stable calibration algorithms that motivate the application of the relevant modeling schemes.

  12. MDI Biological Laboratory Arsenic Summit: Approaches to Limiting Human Exposure to Arsenic

    OpenAIRE

    Stanton, Bruce A.

    2015-01-01

    This report is the outcome of the meeting: “Environmental and Human Health Consequences of Arsenic”, held at the MDI Biological Laboratory in Salisbury Cove, Maine, August 13–15, 2014. Human exposure to arsenic represents a significant health problem worldwide that requires immediate attention according to the World Health Organization (WHO). One billion people are exposed to arsenic in food and more than 200 million people ingest arsenic via drinking water at concentrations greater than inte...

  13. Identification of a potent endothelium-derived angiogenic factor.

    Directory of Open Access Journals (Sweden)

    Vera Jankowski

    Full Text Available The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N=6 were sufficient to induce angiogenic and proliferative effects (1.34 ± 0.26 nmol L(-1. In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor.

  14. Peripheral blood brain-derived neurotrophic factor in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, K; Vinberg, M; Kessing, L V

    2016-01-01

    Peripheral blood brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in bipolar disorder, speculated to mirror alterations in brain expression of BDNF. The research area is rapidly evolving; however, recent...... investigations have yielded conflicting results with substantial variation in outcomes, highlighting the need to critically assess the state of current evidence. The aims of the study were to investigate differences in peripheral blood BDNF concentrations between bipolar disorder patients and healthy control...... subjects and between affective states in bipolar disorder patients, including assessment of the effect of treatment of acute episodes on BDNF levels. A systematic review of English language studies without considering publication status was conducted in PubMed (January 1950-November 2014), Embase (1974...

  15. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes

    DEFF Research Database (Denmark)

    Krabbe, K. S.; Nielsen, A. R.; Krogh-Madsen, R.

    2006-01-01

    Aims/hypothesis  Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore...... explored whether BDNF plays a role in human glucose metabolism. Subjects and methods  We included (Study 1) 233 humans divided into four groups depending on presence or absence of type 2 diabetes and presence or absence of obesity; and (Study 2) seven healthy volunteers who underwent both a hyperglycaemic...... and a hyperinsulinaemic-euglycaemic clamp. Results  Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism...

  16. S100B protein, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in human milk.

    Directory of Open Access Journals (Sweden)

    Ruisong Li

    Full Text Available Human milk contains a wide variety of nutrients that contribute to the fulfillment of its functions, which include the regulation of newborn development. However, few studies have investigated the concentrations of S100B protein, brain-derived neurotrophic factor (BDNF, and glial cell line-derived neurotrophic factor (GDNF in human milk. The associations of the concentrations of S100B protein, BDNF, and GDNF with maternal factors are not well explored.To investigate the concentrations of S100B protein, BDNF, and GDNF in human milk and characterize the maternal factors associated with their levels in human milk, human milk samples were collected at days 3, 10, 30, and 90 after parturition. Levels of S100B protein, BDNF, and GDNF, and their mRNAs in the samples were detected. Then, these concentrations were compared with lactation and other maternal factors. S100B protein levels in human milk samples collected at 3, 10, 30, and 90 d after parturition were 1249.79±398.10, 1345.05±539.16, 1481.83±573.30, and 1414.39±621.31 ng/L, respectively. On the other hand, the BDNF concentrations in human milk samples were 10.99±4.55, 13.01±5.88, 13.35±6.43, and 2.83±5.47 µg/L, while those of GDNF were 10.90±1.65, 11.38±1., 11.29±3.10, and 11.40±2.21 g/L for the same time periods. Maternal post-pregnancy body mass index was positively associated with S100B levels in human milk (r = 0.335, P = 0.030<0.05. In addition, there was a significant correlation between the levels of S100B protein and BDNF (z = 2.09, P = 0.037<0.05. Delivery modes were negatively associated with the concentration of GDNF in human milk.S100B protein, BDNF, and GDNF are present in all samples of human milk, and they may be responsible for the long term effects of breast feeding.

  17. Immune sensitization to methylene diphenyl diisocyanate (MDI resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses

    Directory of Open Access Journals (Sweden)

    Redlich Carrie A

    2011-03-01

    Full Text Available Abstract Background Methylene diphenyl diisocyanate (MDI, a reactive chemical used for commercial polyurethane production, is a well-recognized cause of occupational asthma. The major focus of disease prevention efforts to date has been respiratory tract exposure; however, skin exposure may also be an important route for inducing immune sensitization, which may promote subsequent airway inflammatory responses. We developed a murine model to investigate pathogenic mechanisms by which MDI skin exposure might promote subsequent immune responses, including respiratory tract inflammation. Methods Mice exposed via the skin to varying doses (0.1-10% w/v of MDI diluted in acetone/olive oil were subsequently evaluated for MDI immune sensitization. Serum levels of MDI-specific IgG and IgE were measured by enzyme-linked immunosorbant assay (ELISA, while respiratory tract inflammation, induced by intranasal delivery of MDI-mouse albumin conjugates, was evaluated based on bronchoalveolar lavage (BAL. Autologous serum IgG from "skin only" exposed mice was used to detect and guide the purification/identification of skin proteins antigenically modified by MDI exposure in vivo. Results Skin exposure to MDI resulted in specific antibody production and promoted subsequent respiratory tract inflammation in animals challenged intranasally with MDI-mouse albumin conjugates. The degree of (secondary respiratory tract inflammation and eosinophilia depended upon the (primary skin exposure dose, and was maximal in mice exposed to 1% MDI, but paradoxically limited in mice receiving 10-fold higher doses (e.g. 10% MDI. The major antigenically-modified protein at the local MDI skin exposure site was identified as albumin, and demonstrated biophysical changes consistent with MDI conjugation. Conclusions MDI skin exposure can induce MDI-specific immune sensitivity and promote subsequent respiratory tract inflammatory responses and thus, may play an important role in MDI asthma

  18. Brain-derived neurotrophic factor: role in depression and suicide

    Directory of Open Access Journals (Sweden)

    Yogesh Dwivedi

    2009-08-01

    Full Text Available Yogesh DwivediPsychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF, one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF. This has led to the proposal of the “neurotrophin hypothesis of depression”. Increasing evidence demonstrates that suicidal behavior is also associated with lower expression of BDNF, which may be independent from depression. Recent genetic studies also support a link of BDNF to depression/suicidal behavior. Not only BDNF, but abnormalities in its cognate receptor tropomycin receptor kinase B (TrkB and its splice variant (TrkB.T1 have also been reported in depressed/suicidal patients. It has been suggested that epigenetic modulation of the Bdnf and Trkb genes may contribute to their altered expression and functioning. More recently, impairment in the functioning of pan75 neurotrophin receptor has been reported in suicide brain specimens. pan75 neurotrophin receptor is a low-affinity neurotrophin receptor that, when expressed in conjunction with low availability of neurotropins/Trks, induces apoptosis. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior. This review focuses on the critical evidence demonstrating the involvement of BDNF in depression and suicide.Keywords: BDNF, neurotrophins, p75NTR, Trk receptor, depression, antidepressants, suicide, genetics, epigenetics

  19. OKORLEY .mdi

    African Journals Online (AJOL)

    USER

    running down due to the Lethal Yellowing-type disease commonly known as Cape St. Paul Wilt Disease .... et al, 1998). The methods either aim at reducing the population of the insect vector or preventing re-infestation by cutting and replacing with. CSPWD-resistant varieties. A hybrid ... The farmers (91.5 %) knew what the.

  20. Brain-derived neurotrophic factor enhances conditioned taste aversion retention.

    Science.gov (United States)

    Castillo, Diana V; Figueroa-Guzmán, Yazmín; Escobar, Martha L

    2006-01-05

    Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that induction of long-term potentiation (LTP) in the projection from the basolateral nucleus of the amygdala (Bla) to the IC, previous to CTA training, enhances the retention of this task. Recently, we found that intracortical microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the Bla-IC projection of adult rats in vivo. In this work, we present experimental data showing that intracortical microinfusion of BDNF previous to CTA training enhances the retention of this task. These findings support the concept that BDNF may contribute to memory-related functions performed by a neocortical area, playing a critical role in long-term synaptic plasticity.

  1. Signal transduction by the platelet-derived growth factor receptor

    International Nuclear Information System (INIS)

    Williams, L.T.; Escobedo, J.A.; Keating, M.T.; Coughlin, S.R.

    1988-01-01

    The mitogenic effects of platelet-derived growth factor (PDGF) are mediated by the PDGF receptor. The mouse PDGF receptor was recently purified on the basis of its ability to become tyrosine phosphorylated in response to the A-B human platelet form of PDGF, and the receptor amino acid sequence was determined from a full-length cDNA clone. Both the human and mouse receptor cDNA sequences have been expressed in Chinese hamster ovary fibroblast (CHO) cells that normally lack PDGF receptors. This paper summarizes recent results using this system to study signal transduction by the PDGF receptor. Some of the findings show that the KI domain of the PDGF receptor plays an important role in the stimulation of DNA synthesis by PDGF. Surprisingly, the kinase insert region is not essential for PDGF stimulation of PtdIns turnover, pH change, increase in cellular calcium, and receptor autophosphorylation. In addition, PDGF stimulates a conformational change in the receptor

  2. Effect of processing temperature on the bitumen/MDI-PEG reactivity

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Alfonso, M.J.; Partal, P.; Navarro, F.J.; Garcia-Morales, M. [Departamento de Ingenieria Quimica, Facultad de Ciencias Experimentales, Campus de ' El Carmen' , Universidad de Huelva, 21071, Huelva (Spain); Bordado, J.C.M. [Chemical and Biological Engineering Department, IBB, Instituto Superior Tecnico, Av. Rovisco Pais 1049-001 Lisbon (Portugal); Diogo, A.C. [Materials Engineering Department, Instituto Superior Tecnico, Av. Rovisco Pais 1049-001 Lisbon (Portugal)

    2009-04-15

    Reactive polymers are lately gaining acceptance to give added value to a residue of the crude oil refining process such as bitumen. The resulting material should display enhanced mechanical properties to be considered for advanced applications in construction. In the present paper, we report the effect of processing temperature on the reaction between bitumen compounds and an isocyanate-based reactive polymer, synthesized by reaction of polymeric MDI (4,4'-diphenylmethane diisocyanate) with a low molecular weight polyethylene-glycol (PEG). Rheokinetics experiments, viscosity measurements at 60 C, atomic force microscopy (AFM) characterization, thin layer chromatography (TLC-FID) analysis and thermogravimetric studies (TGA) were performed on the reactive polymer and on samples of MDI-PEG modified bitumen containing 2 wt.% of the polymer. Results showed the existence of an optimum processing temperature arisen as a consequence of opposite effects: microstructural availability for the formation of a polymer-bitumen network, reaction ability and polymer thermal degradation. Consequently, this study aims to serve as a guideline for the refining and asphalt industries facing the stage of selecting the optimum processing parameters. (author)

  3. Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived melanocyte development.

    Science.gov (United States)

    Kos, L; Aronzon, A; Takayama, H; Maina, F; Ponzetto, C; Merlino, G; Pavan, W

    1999-02-01

    The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met-/-) were analysed. In Met-/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro.

  4. Platelet-derived stromal cell-derived factor-1 is required for the transformation of circulating monocytes into multipotential cells.

    Directory of Open Access Journals (Sweden)

    Noriyuki Seta

    Full Text Available BACKGROUND: We previously described a primitive cell population derived from human circulating CD14(+ monocytes, named monocyte-derived multipotential cells (MOMCs, which are capable of differentiating into mesenchymal and endothelial lineages. To generate MOMCs in vitro, monocytes are required to bind to fibronectin and be exposed to soluble factor(s derived from circulating CD14(- cells. The present study was conducted to identify factors that induce MOMC differentiation. METHODS: We cultured CD14(+ monocytes on fibronectin in the presence or absence of platelets, CD14(- peripheral blood mononuclear cells, platelet-conditioned medium, or candidate MOMC differentiation factors. The transformation of monocytes into MOMCs was assessed by the presence of spindle-shaped adherent cells, CD34 expression, and the potential to differentiate in vitro into mesenchymal and endothelial lineages. RESULTS: The presence of platelets or platelet-conditioned medium was required to generate MOMCs from monocytes. A screening of candidate platelet-derived soluble factors identified stromal cell-derived factor (SDF-1 as a requirement for generating MOMCs. Blocking an interaction between SDF-1 and its receptor CXCR4 inhibited MOMC generation, further confirming SDF-1's critical role in this process. Finally, circulating MOMC precursors were found to reside in the CD14(+CXCR4(high cell population. CONCLUSION: The interaction of SDF-1 with CXCR4 is essential for the transformation of circulating monocytes into MOMCs.

  5. Serum platelet-derived growth factor and fibroblast growth factor in patients with benign and malignant ovarian tumors

    DEFF Research Database (Denmark)

    Madsen, Christine Vestergaard; Steffensen, Karina Dahl; Olsen, Dorte Aalund

    2012-01-01

    New biological markers with predictive or prognostic value are highly warranted in the treatment of ovarian cancer. The platelet-derived growth factor (PDGF) system and fibroblast growth factor (FGF) system are important components in tumor growth and angiogenesis....

  6. Serum brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 levels in children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Bilgiç, Ayhan; Toker, Aysun; Işık, Ümit; Kılınç, İbrahim

    2017-03-01

    It has been suggested that neurotrophins are involved in the etiopathogenesis of attention-deficit/hyperactivity disorder (ADHD). This study aimed to investigate whether there are differences in serum brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and neurotrophin-3 (NTF3) levels between children with ADHD and healthy controls. A total of 110 treatment-naive children with the combined presentation of ADHD and 44 healthy controls aged 8-18 years were enrolled in this study. The severity of ADHD symptoms was determined by scores on the Conners' Parent Rating Scale-Revised Short and Conners' Teacher Rating Scale-Revised Short. The severity of depression and anxiety symptoms of the children were evaluated by the self-report inventories. Serum levels of neurotrophins were measured using commercial enzyme-linked immunosorbent assay kits. The multivariate analysis of covariance (MANCOVA) revealed a significant main effect of groups in the levels of serum neurotrophins, an effect that was independent of age, sex, and the severity of the depression and anxiety. The analysis of covariance (ANCOVA) indicated that the mean serum GDNF and NTF3 levels of ADHD patients were significantly higher than that of controls. However, serum BDNF and NGF levels did not show any significant differences between groups. No correlations between the levels of serum neurotrophins and the severity of ADHD were observed. These results suggest that elevated serum GDNF and NTF3 levels may be related to ADHD in children.

  7. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization

    Directory of Open Access Journals (Sweden)

    Xue-man Lv

    2016-01-01

    Full Text Available The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 µg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

  8. Psychometric evaluation of the Major Depression Inventory (MDI) as depression severity scale using the LEAD (Longitudinal Expert Assessment of All Data) as index of validity

    DEFF Research Database (Denmark)

    Bech, Per; Timmerby, N; Martiny, K

    2015-01-01

    BACKGROUND: The Major Depression Inventory (MDI) was developed to cover the universe of depressive symptoms in DSM-IV major depression as well as in ICD-10 mild, moderate, and severe depression. The objective of this study was to evaluate the standardization of the MDI as a depression severity......-IV major depression. The conventional VAS scores for no, mild, moderate, and severe depression were used for the standardization of the MDI. RESULTS: The inter-correlation for the MDI with the clinician ratings (VAS, MES, HAM-D17 and HAM-D6) increased over the rating weeks in terms of Pearson coefficients....... After nine weeks of therapy the coefficient ranged from 0.74 to 0.83. Using the clinician-rated VAS depression severity scale, the conventional MDI cut-off scores for no or doubtful depression, and for mild, moderate and severe depression were confirmed. CONCLUSIONS: Using the VAS as index of external...

  9. Investigation of Quasi-periodic Solar Oscillations in Sunspots Based on SOHO/MDI Magnetograms

    Science.gov (United States)

    Kallunki, J.; Riehokainen, A.

    2012-10-01

    In this work we study quasi-periodic solar oscillations in sunspots, based on the variation of the amplitude of the magnetic field strength and the variation of the sunspot area. We investigate long-period oscillations between three minutes and ten hours. The magnetic field synoptic maps were obtained from the SOHO/MDI. Wavelet (Morlet), global wavelet spectrum (GWS) and fast Fourier transform (FFT) methods are used in the periodicity analysis at the 95 % significance level. Additionally, the quiet Sun area (QSA) signal and an instrumental effect are discussed. We find several oscillation periods in the sunspots above the 95 % significance level: 3 - 5, 10 - 23, 220 - 240, 340 and 470 minutes, and we also find common oscillation periods (10 - 23 minutes) between the sunspot area variation and that of the magnetic field strength. We discuss possible mechanisms for the obtained results, based on the existing models for sunspot oscillations.

  10. The dynamic quiet solar corona: 4 days of joint observing with MDI and EIT

    Science.gov (United States)

    Schrijver, C. J.; Shine, R. A.; Hurlburt, N. E.; Tarbell, T. D.; Lemen, J. R.

    1997-01-01

    The analysis of a sequence of joint extreme ultraviolet imaging telescope (EIT) Fe XII and Michelson Doppler imager (MDI) magnetogram observations of the quiet sun near disk center is presented. It was found that: all the emerging flux above the threshold of approximately 10(sup 17) Mx is associated with enhanced coronal emissions; loop systems between the polarities in ephemeral regions remain visible up to separations of 10000 up to 30000 km; brightenings between approaching opposite polarity network concentrations form when the concentrations are between 5000 and 25000 km apart, and that faint connections up to 40000 km in length form as sets of concentrations of the same polarity coagulate. The coronal emission over patches of the quiet sun depends on the total flux in connected concentrations, on their distance and on the positions and strengths of neighboring concentrations.

  11. Identification of a potent endothelium-derived angiogenic factor

    DEFF Research Database (Denmark)

    Jankowski, Vera; Tölle, Markus; Tran, Thi Nguyet Anh

    2013-01-01

    The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U) from the secretome of human endothelial cells. The angiogenic effect of the endothelia...

  12. Investigating the reactivity of pMDI with wood cell walls using high-resolution solution-state NMR spectroscopy

    Science.gov (United States)

    Daniel J. Yelle; John Ralph; Charles R. Frihart

    2009-01-01

    The objectives of this study are the following: (1) Use solution-state NMR to assign contours in HSQC spectra of the reaction products between pMDI model compounds and: (a) lignin model compounds, (b) milled-wood lignin, (c) ball-milled wood, (d) microtomed loblolly pine; (2) Determine where and to what degree urethane formation occurs with loblolly pine cell wall...

  13. Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor.

    Directory of Open Access Journals (Sweden)

    Michelle E LeBlanc

    Full Text Available Hepatoma-derived growth factor-related protein-3 (Hdgfrp3 or HRP-3 was recently reported as a neurotrophic factor and is upregulated in hepatocellular carcinoma to promote cancer cell survival. Here we identified HRP-3 as a new endothelial ligand and characterized its in vitro and in vivo functional roles and molecular signaling. We combined open reading frame phage display with multi-round in vivo binding selection to enrich retinal endothelial ligands, which were systematically identified by next generation DNA sequencing. One of the identified endothelial ligands was HRP-3. HRP-3 expression in the retina and brain was characterized by Western blot and immunohistochemistry. Cell proliferation assay showed that HRP-3 stimulated the growth of human umbilical vein endothelial cells (HUVECs. HRP-3 induced tube formation of HUVECs in culture. Wound healing assay indicated that HRP-3 promoted endothelial cell migration. HRP-3 was further confirmed for its in vitro angiogenic activity by spheroid sprouting assay. HRP-3 extrinsically activated the extracellular-signal-regulated kinase ½ (ERK1/2 pathway in endothelial cells. The angiogenic activity of HRP-3 was independently verified by mouse cornea pocket assay. Furthermore, in vivo Matrigel plug assay corroborated HRP-3 activity to promote new blood vessel formation. These results demonstrated that HRP-3 is a novel angiogenic factor.

  14. Association assessment of platelet derived growth factor B gene ...

    African Journals Online (AJOL)

    Shayesteh Rezayani

    2017-04-21

    Apr 21, 2017 ... susceptibility and environmental risk factors and their interactions. [1] and starts .... Germany) as internal control, and 30 lM of each specific primer. (Eurofins .... thank the Arya Tina Gene company for recruiting study subjects.

  15. The role of macrophage derived growth factors in pulmonary fibrosis

    International Nuclear Information System (INIS)

    Pickrell, J.A.; Jarpe, M.; Benson, J.M.; Henderson, R.F.

    1988-01-01

    Factors released from rat alveolar macrophages exposed to high (95 μg/mL) concentrations of the fibrogenic agent, nickel subsulfide, were found to inhibit the proliferation of cultured lung epithelial cells and stimulate the growth of fibroblasts. Such factors, if present in the alveoli of rats exposed by inhalation to nickel subsulfide in vivo, may play a role in inhibiting re-epithelization of nickel-damaged lungs and in stimulating fibroblast proliferation, leading to pulmonary fibrosis. (author)

  16. A metabolic derivation of tritium transfer factors in animal products

    International Nuclear Information System (INIS)

    Galeriu, D.; Melintescu, A.; Crout, N. M. J.; Bersford, N. A.; Peterson, S. R.; Hess, M. van

    2001-01-01

    Tritium is a potentially important environmental contaminant arising from the nuclear industry. Because tritium is an isotope of hydrogen, its behaviour in the environment is controlled by the behaviour of hydrogen. Chronic releases of tritium to the atmosphere, in particular, will result in tritium-to-hydrogen (T/H) ratios in plants and animals that are more or less in equilibrium with T/H ratios in the air moisture. Tritium is thus a potentially important contaminant of plant and animal food products. The transfer of tritium from air moisture to plants is quite well understood. In contrast, although a number of regulatory agencies have published transfer coefficient values for diet tritium transfer for a limited number of animal products, a fresh evaluation of these transfers needs to be made In this paper we present an approach for the derivation of tritium transfer coefficients which is based on the metabolism of hydrogen in animals in conjunction with experimental data on tritium transfer. The derived transfer coefficients separately account for transfer to and from free (i.e. water) and organically bound tritium. The predicted transfer coefficients are compared to available data independent of model development. Agreement is good, with the exception of the transfer coefficient for transfer from tritiated water to organically bound tritium in ruminants, which may be attributable to the particular characteristics of ruminant digestion. We show that transfer coefficients will vary in response to the metabolic status of an animal (e.g. stage of lactation, digestibility of diet, etc.) and that the use of a single transfer coefficient from diet to animal product is not appropriate for tritium. It is possible to derive concentration ratio values which relate the concentration of tritiated water and organically bound tritium in an animal product to the corresponding concentrations in the animals diet. These concentration ratios are shown to be less subject to

  17. Coherence factors beyond the BCS expressions—a derivation

    International Nuclear Information System (INIS)

    Gorohovsky, G; Bettelheim, E

    2014-01-01

    We present a derivation of a previously announced result for matrix elements between exact eigenstates of the pairing Hamiltonian. Our results, which generalize the well-known Bardeen–Cooper–Schrieffer (BCS) (Bardeen et al 1957 Phys. Rev. 108 1175; 1957 Phys. Rev. 106 162) expressions for what are known as ‘coherence factors’, are derived based on the Slavnov (1989 Theor. Math. Phys. 79 502) formula for overlaps between Bethe-ansatz states, thus making use of the known connection between the exact diagonalization of the BCS Hamiltonian, due to Richardson (1963 Phys. Lett. 3 277; 1964 Nucl. Phys. A 52 221), and the algebraic Bethe ansatz. The resulting formula has a compact form after a suitable parameterization of the energy plane. Although we apply our method here to the pairing Hamiltonian, it may be adjusted to study what is termed the ‘Sutherland limit’ (Sutherland 1995 Phys. Rev. Lett. 74 816) for exactly solvable models, namely where a macroscopic number of rapidities form a large string. (paper)

  18. Release kinetics of platelet-derived and plasma-derived growth factors from autologous plasma rich in growth factors.

    Science.gov (United States)

    Anitua, Eduardo; Zalduendo, Mari Mar; Alkhraisat, Mohammad Hamdan; Orive, Gorka

    2013-10-01

    Many studies have evaluated the biological effects of platelet rich plasma reporting the final outcomes on cell and tissues. However, few studies have dealt with the kinetics of growth factor delivery by plasma rich in growth factors. Venous blood was obtained from three healthy volunteers and processed with PRGF-Endoret technology to prepare autologous plasma rich in growth factors. The gel-like fibrin scaffolds were then incubated in triplicate, in a cell culture medium to monitor the release of PDGF-AB, VEGF, HGF and IGF-I during 8 days of incubation. A leukocyte-platelet rich plasma was prepared employing the same technology and the concentrations of growth factors and interleukin-1β were determined after 24h of incubation. After each period, the medium was collected, fibrin clot was destroyed and the supernatants were stored at -80°C until analysis. The growth factor delivery is diffusion controlled with a rapid initial release by 30% of the bioactive content after 1h of incubation and a steady state release when almost 70% of the growth factor content has been delivered. Autologous fibrin matrix retained almost 30% of the amount of the growth factors after 8 days of incubation. The addition of leukocytes to the formula of platelet rich plasma did not increase the concentration of the growth factors, while it drastically increased the presence of pro-inflammatory IL-1β. Further studies employing an in vitro inflammatory model would be interesting to study the difference in growth factors and pro-inflammatory cytokines between leukocyte-free and leukocyte-rich platelet rich plasma. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. Probabilistic derivation of the interspecies assessment factor for skin sensitization.

    NARCIS (Netherlands)

    Bil, W; Schuur, A G; Ezendam, J; Bokkers, B G H

    An interspecies sensitization assessment factor (SAF) is used in the quantitative risk assessment (QRA) for skin sensitization when a murine-based NESIL (No Expected Sensitization Induction Level) is taken as point of departure. Several studies showed that, on average, the murine sensitization

  20. Microbiota-Derived Metabolic Factors Reduce Campylobacteriosis in Mice.

    Science.gov (United States)

    Sun, Xiaolun; Winglee, Kathryn; Gharaibeh, Raad Z; Gauthier, Josee; He, Zhen; Tripathi, Prabhanshu; Avram, Dorina; Bruner, Steven; Fodor, Anthony; Jobin, Christian

    2018-05-01

    Campylobacter jejuni, a prevalent foodborne bacterial pathogen, exploits the host innate response to induce colitis. Little is known about the roles of microbiota in C jejuni-induced intestinal inflammation. We investigated interactions between microbiota and intestinal cells during C jejuni infection of mice. Germ-free C57BL/6 Il10 -/- mice were colonized with conventional microbiota and infected with a single dose of C jejuni (10 9 colony-forming units/mouse) via gavage. Conventional microbiota were cultured under aerobic, microaerobic, or anaerobic conditions and orally transplanted into germ-free Il10 -/- mice. Colon tissues were collected from mice and analyzed by histology, real-time polymerase chain reaction, and immunoblotting. Fecal microbiota and bile acids were analyzed with 16S sequencing and high-performance liquid chromatography with mass spectrometry, respectively. Introduction of conventional microbiota reduced C jejuni-induced colitis in previously germ-free Il10 -/- mice, independent of fecal load of C jejuni, accompanied by reduced activation of mammalian target of rapamycin. Microbiota transplantation and 16S ribosomal DNA sequencing experiments showed that Clostridium XI, Bifidobacterium, and Lactobacillus were enriched in fecal samples from mice colonized with microbiota cultured in anaerobic conditions (which reduce colitis) compared with mice fed microbiota cultured under aerobic conditions (susceptible to colitis). Oral administration to mice of microbiota-derived secondary bile acid sodium deoxycholate, but not ursodeoxycholic acid or lithocholic acid, reduced C jejuni-induced colitis. Depletion of secondary bile acid-producing bacteria with antibiotics that kill anaerobic bacteria (clindamycin) promoted C jejuni-induced colitis in specific pathogen-free Il10 -/- mice compared with the nonspecific antibiotic nalidixic acid; colitis induction by antibiotics was associated with reduced level of luminal deoxycholate. We identified a

  1. Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.

    Science.gov (United States)

    Selheim, F; Holmsen, H; Vassbotn, F S

    1999-08-15

    We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.

  2. Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

    Directory of Open Access Journals (Sweden)

    Joko Widodo

    2016-05-01

    Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

  3. BIPOLAR MAGNETIC REGIONS ON THE SUN: GLOBAL ANALYSIS OF THE SOHO/MDI DATA SET

    International Nuclear Information System (INIS)

    Stenflo, J. O.; Kosovichev, A. G.

    2012-01-01

    The magnetic flux that is generated by dynamo processes inside the Sun emerges in the form of bipolar magnetic regions. The properties of these directly observable signatures of the dynamo can be extracted from full-disk solar magnetograms. The most homogeneous, high-quality synoptic data set of solar magnetograms has been obtained with the Michelson Doppler Imager (MDI) instrument on the Solar and Heliospheric Observatory spacecraft during 1995-2011. We have developed an IDL program that has, when applied to the 73,838 magnetograms of the MDI data set, automatically identified 160,079 bipolar magnetic regions that span a range of scale sizes across nearly four orders of magnitude. The properties of each region have been extracted and statistically analyzed, in particular with respect to the polarity orientations of the bipolar regions, including their tilt-angle distributions and their violations of Hale's polarity law. The latitude variation of the average tilt angles (with respect to the E-W direction), which is known as Joy's law, is found to closely follow the relation 32. 0 1 × sin (latitude). There is no indication of a dependence on region size that one may expect if the tilts were produced by the Coriolis force during the buoyant rise of flux loops from the tachocline region. A few percent of all regions have orientations that violate Hale's polarity law. We show explicit examples, from different phases of the solar cycle, where well-defined medium-size bipolar regions with opposite polarity orientations occur side by side in the same latitude zone in the same magnetogram. Such oppositely oriented large bipolar regions cannot be part of the same toroidal flux system, but different flux systems must coexist at any given time in the same latitude zones. These examples are incompatible with the paradigm of coherent, subsurface toroidal flux ropes as the source of sunspots, and instead show that fluctuations must play a major role at all scales for the

  4. Structure activity relationships of quinoxalin-2-one derivatives as platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors, derived from molecular modeling.

    Science.gov (United States)

    Mori, Yoshikazu; Hirokawa, Takatsugu; Aoki, Katsuyuki; Satomi, Hisanori; Takeda, Shuichi; Aburada, Masaki; Miyamoto, Ken-ichi

    2008-05-01

    We previously reported a quinoxalin-2-one compound (Compound 1) that had inhibitory activity equivalent to existing platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors. Lead optimization of Compound 1 to increase its activity and selectivity, using structural information regarding PDGFbeta R-ligand interactions, is urgently needed. Here we present models of the PDGFbeta R kinase domain complexed with quinoxalin-2-one derivatives. The models were constructed using comparative modeling, molecular dynamics (MD) and ligand docking. In particular, conformations derived from MD, and ligand binding site information presented by alpha-spheres in the pre-docking processing, allowed us to identify optimal protein structures for docking of target ligands. By carrying out molecular modeling and MD of PDGFbeta R in its inactive state, we obtained two structural models having good Compound 1 binding potentials. In order to distinguish the optimal candidate, we evaluated the structural activity relationships (SAR) between the ligand-binding free energies and inhibitory activity values (IC50 values) for available quinoxalin-2-one derivatives. Consequently, a final model with a high SAR was identified. This model included a molecular interaction between the hydrophobic pocket behind the ATP binding site and the substitution region of the quinoxalin-2-one derivatives. These findings should prove useful in lead optimization of quinoxalin-2-one derivatives as PDGFb R inhibitors.

  5. Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages.

    Directory of Open Access Journals (Sweden)

    Francesco Oddone

    Full Text Available To investigate the serum levels of Brain Derived Neurotrophic Factor (BDNF and Nerve Growth Factor (NGF in patients affected by primary open angle glaucoma with a wide spectrum of disease severity compared to healthy controls and to explore their relationship with morphological and functional glaucoma parameters.45 patients affected by glaucoma at different stages and 15 age-matched healthy control subjects underwent visual field testing, peripapillary retinal nerve fibre layer thickness measurement using Spectral Domain Optical Coherence Tomography and blood collection for both neurotrophins detection by Enzyme-Linked Immunosorbent Assay. Statistical analysis and association between biostrumental and biochemical data were investigated.Serum levels of BDNF in glaucoma patients were significantly lower than those measured in healthy controls (261.2±75.0 pg/ml vs 313.6±79.6 pg/ml, p = 0.03. Subgroups analysis showed that serum levels of BDNF were significantly lower in early (253.8±40.7 pg/ml, p = 0.019 and moderate glaucoma (231.3±54.3 pg/ml, p = 0.04 but not in advanced glaucoma (296.2±103.1 pg/ml, p = 0.06 compared to healthy controls. Serum levels of NGF in glaucoma patients were significantly lower than those measured in the healthy controls (4.1±1 pg/mL vs 5.5±1.2 pg/mL, p = 0.01. Subgroups analysis showed that serum levels of NGF were significantly lower in early (3.5±0.9 pg/mL, p = 0.0008 and moderate glaucoma (3.8±0.7 pg/ml, p<0.0001 but not in advanced glaucoma (5.0±0.7 pg/ml, p = 0.32 compared to healthy controls. BDNF serum levels were not related to age, visual field mean deviation or retinal nerve fibre layer thickness either in glaucoma or in controls while NGF levels were significantly related to visual field mean deviation in the glaucoma group (r2 = 0.26, p = 0.004.BDNF and NGF serum levels are reduced in the early and moderate glaucoma stages, suggesting the possibility that both factors could be further investigated

  6. Higher lung deposition with Respimat® Soft Mist™ Inhaler than HFA-MDI in COPD patients with poor technique

    Directory of Open Access Journals (Sweden)

    Peter Brand

    2008-08-01

    Full Text Available Peter Brand1, Bettina Hederer2, George Austen3, Helen Dewberry3, Thomas Meyer41RWTH, Aachen, Germany; 2Boehringer Ingelheim, Ingelheim, Germany; 3Boehringer Ingelheim, Bracknell, UK; 4Inamed Research, Gauting, GermanyAbstract: Aerosols delivered by Respimat® Soft Mist™ Inhaler (SMI are slower-moving and longer-lasting than those from pressurized metered-dose inhalers (pMDIs, improving the efficiency of pulmonary drug delivery to patients. In this four-way cross-over study, adults with chronic obstructive pulmonary disease (COPD and with poor pMDI technique received radiolabelled Berodual® (fenoterol hydrobromide 50 µg/ipratropium bromide 20 µg via Respimat® SMI or hydrofluoroalkane (HFA-MDI (randomized order on test days 1 and 2, with no inhaler technique training. The procedure was repeated on test days 3 and 4 after training. Deposition was measured by gamma scintigraphy. All 13 patients entered (9 males, mean age 62 years; FEV1 46% of predicted inhaled too fast at screening (peak inspiratory flow rate [IF]: 69–161 L/min. Whole lung deposition was higher with Respimat® SMI than with pMDI for untrained (37% of delivered dose vs 21% of metered dose and trained patients (53% of delivered vs 21% of metered dose (pSign-Test = 0.15; pANOVA< 0.05. Training also improved inhalation profiles (slower average and peak IF as well as longer breath-hold time. Drug delivery to the lungs with Respimat® SMI is more efficient than with pMDI, even with poor inhaler technique. Teaching patients to hold their breath as well as to inhale slowly and deeply increased further lung deposition using Respimat® SMI.Keywords: chronic obstructive pulmonary disease, drug delivery, inhalation, metered-dose inhaler, poor inhalation technique, training

  7. Airborne concentrations of methylene diphenyl diisocyanate (MDI) in North American wood mills during the manufacturing of oriented strand board (OSB).

    Science.gov (United States)

    Karoly, William J; Flatley, John J; Stevenson, Ralph D; Bowers, John D

    2004-12-01

    Air monitoring data were collected from industrial hygiene surveys over an 8-year period in oriented strand board (OSB) mills. Personal samples were taken to evaluate potential employee exposures to MDI. Area samples were taken to determine the effectiveness of control measures used in the mills to prevent fugitive emissions of wood dust, MDI, and MDI-coated wood dust from the OSB manufacturing process. Personal sampling results (578 samples covering 11 different job categories) ranged from 0.0002-0.524 mg/m3, with a GM = 0.001 and GSD = 3.71. Area sampling results (1657 samples covering 14 stationary locations in the mills) ranged from 0.0002-2.5 mg/m3, with a GM = 0.004 and GSD = 5.52. The statistical range of the data suggests high variability. While exposures to MDI above the established limits (0.051 mg/m3, 8-hour time-weighted average, 0.2 mg/m3, ceiling) can and do occur when engineering controls are not maintained and/or proper work practices and personal protective equipment are not followed/used for certain high exposure potential tasks, the data indicate that over 97% of the personal and 92% of the area sampling results are less than 0.051 mg/m3. Wipe testing was performed to determine the presence of removable, unreacted diisocyanates (NCO functional groups)from various surfaces. Positive results were found in about 13% of the wipe tests on surfaces confined to the blender, forming line, and hopper deck process areas.

  8. Endothelium-derived vasoactive factors and hypertension: possible roles in pathogenesis and as treatment targets

    DEFF Research Database (Denmark)

    Félétou, Michel; Köhler, Ralf; Vanhoutte, Paul M

    2010-01-01

    Endothelial cells regulate vascular tone by releasing various contracting and relaxing factors including nitric oxide (NO), arachidonic acid metabolites (derived from cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases), reactive oxygen species, and vasoactive peptides. Additionally...

  9. 14C-Methylenebisphenylisocyanate (14C-MDI). Study of absorption after single dermal and intradermal administration in rats

    International Nuclear Information System (INIS)

    Leibold, E.; Hoffmann, H.D.; Hildebrand, B.

    1999-01-01

    The absorption, distribution and excretion of radioactivity was studied in groups of four male Wistar rats following a single dermal and intradermal administration of 14 C- Methylenebisphenylisocyanate ( 14 C-MDI) at nominal dose levels of 4.0 and 0.4 mg/cm 2 for dermal administration and 0.4 mg/animal for intradermal administration. These dose levels nominally corresponded to 40 and 4.0 mg/animal for dermal administration. Considering the animal weights, dose levels corresponded to about 140 and 14 mg/kg body weight (dermal administration) and 1.4 mg/kg body weight (intradermal administration). In the experiments with dermal administration, animals were exposed for 8 hours and sacrificed 8, 24 or 120 h after beginning of exposure. In the experiment with intradermal administration, animals were sacrificed 120 h after treatment. After dermal administration of 14 C-MDI, mean recoveries of radioactivity from all dose groups were in the range from 97.86 to 108.07% of the total radioactivity administered. Generally, the largest proportion of radioactivity was found at the application site and dressing. The total amount of radioactivity absorbed (including excreta, cage wash, tissues/organs and carcass) increased with increasing sacrifice time. Dermal absorption was very low and quantitatively similar at both dose levels; maximally ca. 0.9 % of the applied radioactivity was absorbed. After intradermal administration of 14 C-MDI, the mean recovery of radioactivity was 100.90 % of the radioactivity administered. The largest proportion of radioactivity was found at the application site. The total amount of radioactivity absorbed (including excreta, cage wash, tissues/organs and carcass) amounted to about 26 % of the radioactivity applied. Irrespective of the mode of administration of 1 4C -MDI, concentrations of radioactivity in tissues and organs generally were below 1 μg Eq/g at 120 h after administration. In summary, the results of this study comparing systemic

  10. Effect of cigarette smoke on monocyte procoagulant activity: Focus on platelet-derived brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

    Amadio, Patrizia; Baldassarre, Damiano; Sandrini, Leonardo; Weksler, Babette B; Tremoli, Elena; Barbieri, Silvia S

    2017-01-01

    Cigarette smoke (CS) activates platelets, promotes vascular dysfunction, and enhances Tissue Factor (TF) expression in blood monocytes favoring pro-thrombotic states. Brain-derived neurotrophic factor (BDNF), a member of the family of neurotrophins involved in survival, growth, and maturation of neurons, is released by activated platelets (APLTs) and plays a role in the cardiovascular system. The effect of CS on circulating levels of BDNF is controversial and the function of circulating BDNF in atherothrombosis is not fully understood. Here, we have shown that human platelets, treated with an aqueous extract of CS (CSE), released BDNF in a dose-dependent manner. In addition, incubation of human monocytes with BDNF or with the supernatant of platelets activated with CSE increased TF activity by a Tropomyosin receptor kinase B (TrkB)-dependent mechanism. Finally, comparing serum and plasma samples of 12 male never smokers (NS) and 29 male active smokers (AS) we observed a significant increase in microparticle-associated TF activity (MP-TF) as well as BDNF in AS, while in serum, BDNF behaved oppositely. Taken together these findings suggest that platelet-derived BDNF is involved in the regulation of TF activity and that CS plays a role in this pathway by favoring a pro-atherothrombotic state.

  11. Expression of platelet-derived growth factor and its receptors in proliferative disorders of fibroblastic origin.

    OpenAIRE

    Smits, A.; Funa, K.; Vassbotn, F. S.; Beausang-Linder, M.; af Ekenstam, F.; Heldin, C. H.; Westermark, B.; Nistér, M.

    1992-01-01

    Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of connective tissue-derived cells in vitro. Less is known about its functions in vivo, and the role of PDGF in the development of human tumors has not been clarified. The authors have investigated the occurrence of PDGF and PDGF receptors in a series of proliferative disorders of fibroblastic origin using immunohistochemical and in situ hybridization techniques. High expression of PDGF beta-receptor mRNA and protei...

  12. Theobromine up-regulates cerebral brain-derived neurotrophic factor and facilitates motor learning in mice

    OpenAIRE

    Yoneda, Mitsugu; Sugimoto, Naotoshi; Katakura, Masanori; Matsuzaki, Kentaro; Tanigami, Hayate; Yachie, Akihiro; Ohno-Shosaku, Takako; Shido, Osamu

    2017-01-01

    Theobromine, which is a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. Theobromine works as a phosphodiesterase (PDE) inhibitor to increase intracellular cyclic adenosine monophosphate (cAMP). cAMP activates the cAMP-response element-binding protein (CREB), which is involved in a large variety of brain processes, including the induction of the brain-derived neurotrophic factor (BDNF). BDNF supports cell survival and neuronal functions, including learning and m...

  13. Adult hippocampus derived soluble factors induce a neuronal-like phenotype in mesenchymal stem cells.

    Science.gov (United States)

    Rivera, Francisco J; Sierralta, Walter D; Minguell, Jose J; Aigner, Ludwig

    2006-10-02

    Bone marrow-derived mesenchymal stem cells (MSCs) are not restricted in their differentiation fate to cells of the mesenchymal lineage. They acquire a neural phenotype in vitro and in vivo after transplantation in the central nervous system. Here we investigated whether soluble factors derived from different brain regions are sufficient to induce a neuronal phenotype in MSCs. We incubated bone marrow-derived MSCs in conditioned medium (CM) derived from adult hippocampus (HCM), cortex (CoCM) or cerebellum (CeCM) and analyzed the cellular morphology and the expression of neuronal and glial markers. In contrast to muscle derived conditioned medium, which served as control, conditioned medium derived from the different brain regions induced a neuronal morphology and the expression of the neuronal markers GAP-43 and neurofilaments in MSCs. Hippocampus derived conditioned medium had the strongest activity. It was independent of NGF or BDNF; and it was restricted to the neuronal differentiation fate, since no induction of the astroglial marker GFAP was observed. The work indicates that soluble factors present in the brain are sufficient to induce a neuronal phenotype in MSCs.

  14. The Behaviour of Small Investors in the Hong Kong Derivatives Markets: A Factor Analysis

    Directory of Open Access Journals (Sweden)

    Tai-Yuen Hon

    2012-12-01

    Full Text Available This paper investigates the behaviour of small investors in Hong Kong’s derivatives markets. The study period covers the global economic crisis of 2011- 2012, and we focus on small investors’ behaviour during and after the crisis. We attempt to identify and analyse the key factors that capture their behaviour in derivatives markets in Hong Kong. The data were collected from 524 respondents via a questionnaire survey. Exploratory factor analysis was employed to analyse the data, and some interesting findings were obtained. Our study enhances our understanding of behavioural finance in the setting of an Asian financial centre, namely Hong Kong.

  15. A modified derivation of the correlation factor in tracer diffusion via vacancy mechanism

    International Nuclear Information System (INIS)

    Koiwa, Masahiro

    1978-01-01

    The average number of site exchanges made by a particular atom-vacancy pair has been calculated. It is found that the number of exchanges is equal to the number of visits to the origin of a random walker; for an infinite fcc lattice the number of exchanges is about 1.345, including the first exchange. This result seems invalidate the assumption of an infinite number of exchanges, which is usually made in the derivation of the correlation factor in diffusion via the vacancy mechanism. A modified derivation of the correlation factor, which takes into account the number of exchanges explicitly, is presented. (author)

  16. The influence of actuator materials and nozzle designs on electrostatic charge of pressurised metered dose inhaler (pMDI) formulations.

    Science.gov (United States)

    Chen, Yang; Young, Paul M; Fletcher, David F; Chan, Hak Kim; Long, Edward; Lewis, David; Church, Tanya; Traini, Daniela

    2014-05-01

    To investigate the influence of different actuator materials and nozzle designs on the electrostatic charge properties of a series of solution metered dose inhaler (pMDI) aerosols. Actuators were manufactured with flat and cone nozzle designs using five different materials from the triboelectric series (Nylon, Polyethylene terephthalate, Polyethylene-High density, Polypropylene copolymer and Polytetrafluoroethylene). The electrostatic charge profiles of pMDI containing beclomethasone dipropionate (BDP) as model drug in HFA-134a propellant, with different concentrations of ethanol were studied. Electrostatic measurements were taken using a modified electrical low-pressure impactor (ELPI) and the deposited drug mass assayed chemically using HPLC. The charge profiles of HFA 134a alone have shown strong electronegativity with all actuator materials and nozzle designs, at an average of -1531.34 pC ± 377.34. The presence of co-solvent ethanol significantly reduced the negative charge magnitude. BDP reduced the suppressing effect of ethanol on the negative charging of the propellant. For all tested formulations, the flat nozzle design showed no significant differences in net charge between different actuator materials, whereas the charge profiles of cone designs followed the triboelectric series. The electrostatic charging profiles from a solution pMDI containing BDP and ethanol can be significantly influenced by the actuator material, nozzle design and formulation components. Ethanol concentration appears to have the most significant impact. Furthermore, BDP interactions with ethanol and HFA have an influence on the electrostatic charge of aerosols. By choosing different combinations of actuator materials and orifice design, the fine particle fractions of formulations can be altered.

  17. Studies on in vitro biostability and blood compatibility of polyurethane potting compound based on aromatic polymeric MDI for extracorporeal devices.

    Science.gov (United States)

    Hridya, V K; Jayabalan, M

    2009-12-01

    Polyurethane potting compound based on aromatic isocyanurate of polymeric MDI, poly propylene glycol (PPG400) and trimethylol propane (TMP) has significant favourable properties, good pot life and setting characteristics. The cured potting compound of this formulation has appreciable thermal stability and mechanical properties. In vitro biostability of cured potting compound has been found to be excellent without any significant degradation in simulated physiological media and chemical environment. Studies on blood-material interaction and cytotoxicity reveal in vitro blood compatibility and compatibility with cells of this potting compound.

  18. A bioactive molecule in a complex wound healing process: platelet-derived growth factor.

    Science.gov (United States)

    Kaltalioglu, Kaan; Coskun-Cevher, Sule

    2015-08-01

    Wound healing is considered to be particularly important after surgical procedures, and the most important wounds related to surgical procedures are incisional, excisional, and punch wounds. Research is ongoing to identify methods to heal non-closed wounds or to accelerate wound healing; however, wound healing is a complex process that includes many biological and physiological events, and it is affected by various local and systemic factors, including diabetes mellitus, infection, ischemia, and aging. Different cell types (such as platelets, macrophages, and neutrophils) release growth factors during the healing process, and platelet-derived growth factor is a particularly important mediator in most stages of wound healing. This review explores the relationship between platelet-derived growth factor and wound healing. © 2014 The International Society of Dermatology.

  19. The predictive value of mental health for long-term sickness absence: the Major Depression Inventory (MDI) and the Mental Health Inventory (MHI-5) compared.

    Science.gov (United States)

    Thorsen, Sannie Vester; Rugulies, Reiner; Hjarsbech, Pernille U; Bjorner, Jakob Bue

    2013-09-17

    Questionnaires are valuable for population surveys of mental health. Different survey instruments may however give different results. The present study compares two mental health instruments, the Major Depression Inventory (MDI) and the Mental Health Inventory (MHI-5), in regard to their prediction of long-term sickness absence. Questionnaire data was collected from N = 4153 Danish employees. The questionnaire included the MDI and the MHI-5. The information of long-term sickness absence was obtained from a register. We used Cox regression to calculate covariance adjusted hazard ratios for long-term sickness absence for both measures. Both the MDI and the MHI-5 had a highly significant prediction of long-term sickness absence. A one standard deviation change in score was associated with an increased risk of long-term sickness absence of 27% for the MDI and 37% for the MHI-5. When both measures were included in the same analysis, the MHI-5 performed best. In general population surveys, the MHI-5 is a better predictor of long-term sickness absence than the MDI.

  20. Production of active pigment epithelium-derived factor inE. coli.

    Science.gov (United States)

    Zhang, Tao; Guan, Ming; Lu, Yuan

    2005-03-01

    Human pigment epithelium-derived factor (PEDF), a neurotrophic factor, is the most potent natural inhibitor of angiogenesis. To produce the active PEDF, the gene coding for the human PEDF protein was expressed in E. coli. The rPEDF protein was expressed at 457 mg l-1 as a soluble protein. The yield of purified GST fusion protein was 14 mg l-1. Purified rPEDF inhibited tube formation in endothelial cells.

  1. Effect of childhood maltreatment and brain-derived neurotrophic factor on brain morphology

    NARCIS (Netherlands)

    van Velzen, Laura S.; Schmaal, Lianne; Jansen, Rick; Milaneschi, Yuri; Opmeer, Esther M.; Elzinga, Bernet M.; van der Wee, Nic J. A.; Veltman, Dick J.; Penninx, Brenda W. J. H.

    2016-01-01

    Childhood maltreatment (CM) has been associated with altered brain morphology, which may partly be due to a direct impact on neural growth, e.g. through the brain-derived neurotrophic factor (BDNF) pathway. Findings on CM, BDNF and brain volume are inconsistent and have never accounted for the

  2. Human obesity associated with an intronic SNP in the brain-derived neurotrophic factor locus

    Science.gov (United States)

    Brain-derived neurotrophic factor (BDNF) plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 ...

  3. Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants

    Science.gov (United States)

    In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. The objective of this study is to compare BDNF concentrations of subjects wi...

  4. Brain-derived neurotrophic factor and addiction: Pathological versus therapeutic effects on drug seeking

    NARCIS (Netherlands)

    Barker, J.M.; Taylor, J.R.; de Vries, T.J.; Peters, J.

    2015-01-01

    Many abused drugs lead to changes in endogenous brain-derived neurotrophic factor (BDNF) expression in neural circuits responsible for addictive behaviors. BDNF is a known molecular mediator of memory consolidation processes, evident at both behavioral and neurophysiological levels. Specific neural

  5. Brain-Derived Neurotrophic Factor Predicts Mortality Risk in Older Women

    DEFF Research Database (Denmark)

    Krabbe, K.S.; Mortensen, E.L.; Avlund, K.

    2009-01-01

    OBJECTIVES To test the hypothesis that low circulating brain-derived neurotrophic factor (BDNF), a secretory member of the neurotrophin family that has a protective role in neurodegeneration and stress responses and a regulatory role in metabolism, predicts risk of all-cause mortality in 85-year...

  6. Decreased levels of brain-derived neurotrophic factor in the remitted state of unipolar depressive disorder

    DEFF Research Database (Denmark)

    Hasselbalch, Jacob; Knorr, U; Bennike, B

    2012-01-01

    Decreased levels of peripheral brain-derived neurotrophic factor (BDNF) have been associated with depression. It is uncertain whether abnormally low levels of BDNF in blood are present beyond the depressive state and whether levels of BDNF are associated with the course of clinical illness....

  7. Axon Guidance of Sympathetic Neurons to Cardiomyocytes by Glial Cell Line-Derived Neurotrophic Factor (GDNF)

    NARCIS (Netherlands)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Hirabayashi, Masumi; Watabe, Kazuhiko; Jimbo, Yasuhiko; Kodama, Itsuo; Komuro, Issei

    2013-01-01

    Molecular signaling of cardiac autonomic innervation is an unresolved issue. Here, we show that glial cell line-derived neurotrophic factor (GDNF) promotes cardiac sympathetic innervation in vitro and in vivo. In vitro, ventricular myocytes (VMs) and sympathetic neurons (SNs) isolated from neonatal

  8. Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI.

    Directory of Open Access Journals (Sweden)

    Cristina Puy

    Full Text Available Factor (F XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα, in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin.Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma.Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP.

  9. The MDI-Mediated Lateral Crosslinking of Polyurethane Copolymer and the Impact on Tensile Properties and Shape Memory Effect

    International Nuclear Information System (INIS)

    Chung, Yong Chan; Chung, Hyang Mi; Choi, Jae Won; Chun, Byoung Chul

    2012-01-01

    The maximum stress and strain at break remained high and stable after MDI-mediated crosslinking. Similarly, shape recovery and shape retention tests also showed excellent and reproducible results. The MDI-mediated crosslinking was responsible for the interesting tensile and shape memory results. Therefore, it was demonstrated in this investigation that the allophanate type crosslinking, unlike previous misleading information, was possible under the mild reaction conditions. Polyurethane (PU) has long been investigated due to its excellent mechanical properties, shape memory effect, and biocompatibility, and was grafted with pendant functional groups to tailor the polymer characteristics without affecting their basic structure. Actually, polyethyleneglycol has been grafted to polyurethane to improve biocompatibility in biomedical applications, and low temperature flexibility could be improved by the pendant naphthol group grafted to PU. In the field of shape memory polyurethane, mechanical and shape memory properties could be improved by terminal crosslinking with glycerol, pentaerythritol, and dextrin. Alternatively, a flexible crosslinking method was devised to demonstrate both high mechanical strength and shape recovery

  10. Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium.

    Science.gov (United States)

    Tunca, Zeliha; Ozerdem, Aysegul; Ceylan, Deniz; Yalçın, Yaprak; Can, Güneş; Resmi, Halil; Akan, Pınar; Ergör, Gül; Aydemir, Omer; Cengisiz, Cengiz; Kerim, Doyuran

    2014-09-01

    Brain-derived neurotrophic factor (BDNF) has been consistently reported to be decreased in mania or depression in bipolar disorders. Evidence suggests that Glial cell line-derived neurotrophic factor (GDNF) has a role in the pathogenesis of mood disorders. Whether GDNF and BDNF act in the same way across different episodes in bipolar disorders is unclear. BDNF and GDNF serum levels were measured simultaneously by enzyme-linked immunosorbent assay (ELISA) method in 96 patients diagnosed with bipolar disorder according to DSM-IV (37 euthymic, 33 manic, 26 depressed) in comparison to 61 healthy volunteers. SCID- I and SCID-non patient version were used for clinical evaluation of the patients and healthy volunteers respectively. Correlations between the two trophic factor levels, and medication dose, duration and serum levels of lithium or valproate were studied across different episodes of illness. Patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. GDNF levels were not distinctive. However GDNF/BDNF ratio was higher in manic state compared to euthymia and healthy controls. Significant negative correlation was observed between BDNF and GDNF levels in euthymic patients. While BDNF levels correlated positively, GDNF levels correlated negatively with lithium levels. Regression analysis confirmed that lithium levels predicted only GDNF levels positively in mania, and negatively in euthymia. Small sample size in different episodes and drug-free patients was the limitation of thestudy. Current data suggests that lithium exerts its therapeutic action by an inverse effect on BDNF and GDNF levels, possibly by up-regulating BDNF and down-regulating GDNF to achieve euthymia. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Liver-derived systemic factors drive β-cell hyperplasia in insulin resistant states

    Energy Technology Data Exchange (ETDEWEB)

    El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument; Liew, Chong Wee; Shadrach, Jennifer L.; Hu, Jiang; Katsuta, Hitoshi; Hollister-Lock, Jennifer; Qian, Weijun; Wagers, Amy J.; Kulkarni, Rohit N.

    2013-02-21

    Integrative organ cross-talk regulates key aspects of energy homeostasis and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that cross-talk between the liver and pancreatic islets modulates β-cell growth in response to insulin resistance, we used the Liver-specific Insulin Receptor Knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, and in vitro islet culture approaches, we demonstrate that humoral, non-neural, non-cell autonomous factor(s) induce β-cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human β-cell proliferation in ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of β-cell growth factors in insulin resistant states.

  12. Evaluation of landslide susceptibility mapping techniques using lidar-derived conditioning factors (Oregon case study

    Directory of Open Access Journals (Sweden)

    Rubini Mahalingam

    2016-11-01

    Full Text Available Landslides are a significant geohazard, which frequently result in significant human, infrastructure, and economic losses. Landslide susceptibility mapping using GIS and remote sensing can help communities prepare for these damaging events. Current mapping efforts utilize a wide variety of techniques and consider multiple factors. Unfortunately, each study is relatively independent of others in the applied technique and factors considered, resulting in inconsistencies. Further, input data quality often varies in terms of source, data collection, and generation, leading to uncertainty. This paper investigates if lidar-derived data-sets (slope, slope roughness, terrain roughness, stream power index, and compound topographic index can be used for predictive mapping without other landslide conditioning factors. This paper also assesses the differences in landslide susceptibility mapping using several, widely used statistical techniques. Landslide susceptibility maps were produced from the aforementioned lidar-derived data-sets for a small study area in Oregon using six representative statistical techniques. Most notably, results show that only a few factors were necessary to produce satisfactory maps with high predictive capability (area under the curve >0.7. The sole use of lidar digital elevation models and their derivatives can be used for landslide mapping using most statistical techniques without requiring additional detailed data-sets that are often difficult to obtain or of lower quality.

  13. Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel

    2014-01-01

    Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case-control desi......Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case......-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3......, levels of BDNF were significantly elevated in bipolar disorder patients in euthymic- (pdifference in BDNF levels...

  14. Platelet-rich plasma derived growth factors contribute to stem cell differentiation in musculoskeletal regeneration

    Science.gov (United States)

    Qian, Yun; Han, Qixin; Chen, Wei; Song, Jialin; Zhao, Xiaotian; Ouyang, Yuanming; Yuan, Weien; Fan, Cunyi

    2017-10-01

    Stem cell treatment and platelet-rich plasma (PRP) therapy are two significant issues in regenerative medicine. Stem cells such as bone marrow mesenchymal stem cells, adipose-derived stem cells and periodontal ligament stem cells can be successfully applied in the field of tissue regeneration. PRP, a natural product isolated from whole blood, can secrete multiple growth factors (GFs) for regulating physiological activities. These GFs can stimulate proliferation and differentiation of different stem cells in injury models. Therefore, combination of both agents receives wide expectations in regenerative medicine, especially in bone, cartilage and tendon repair. In this review, we thoroughly discussed the interaction and underlying mechanisms of platelet-rich plasma derived growth factors with stem cells, and assessed their functions in cell differentiation for musculoskeletal regeneration.

  15. Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Nahyun Choi

    2018-02-01

    Full Text Available Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs. We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif ligand 1 (CXCL1, platelet-derived endothelial cell growth factor (PD-ECGF, and platelet-derived growth factor-C (PDGF-C. Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2 phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.

  16. Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

    Science.gov (United States)

    Choi, Nahyun; Shin, Soyoung; Song, Sun U.; Sung, Jong-Hyuk

    2018-01-01

    Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration. PMID:29495622

  17. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans

    DEFF Research Database (Denmark)

    Huang, T; Larsen, K T; Ried-Larsen, M

    2014-01-01

    The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles...... studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies....

  18. Platelet-Rich Plasma Derived Growth Factors Contribute to Stem Cell Differentiation in Musculoskeletal Regeneration

    OpenAIRE

    Yun Qian; Yun Qian; Qixin Han; Wei Chen; Wei Chen; Jialin Song; Jialin Song; Xiaotian Zhao; Yuanming Ouyang; Yuanming Ouyang; Weien Yuan; Cunyi Fan

    2017-01-01

    Stem cell treatment and platelet-rich plasma (PRP) therapy are two significant issues in regenerative medicine. Stem cells such as bone marrow mesenchymal stem cells, adipose-derived stem cells and periodontal ligament stem cells can be successfully applied in the field of tissue regeneration. PRP, a natural product isolated from whole blood, can secrete multiple growth factors (GFs) for regulating physiological activities. These GFs can stimulate proliferation and differentiation of differen...

  19. Brain-derived neurotrophic factor promoter methylation and cortical thickness in recurrent major depressive disorder

    OpenAIRE

    Na, Kyoung-Sae; Won, Eunsoo; Kang, June; Chang, Hun Soo; Yoon, Ho-Kyoung; Tae, Woo Suk; Kim, Yong-Ku; Lee, Min-Soo; Joe, Sook-Haeng; Kim, Hyun; Ham, Byung-Joo

    2016-01-01

    Recent studies have reported that methylation of the brain-derived neurotrophic factor (BDNF) gene promoter is associated with major depressive disorder (MDD). This study aimed to investigate the association between cortical thickness and methylation of BDNF promoters as well as serum BDNF levels in MDD. The participants consisted of 65 patients with recurrent MDD and 65 age- and gender-matched healthy controls. Methylation of BDNF promoters and cortical thickness were compared between the gr...

  20. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor

    OpenAIRE

    Szuhany, Kristin L.; Bugatti, Matteo; Otto, Michael W.

    2014-01-01

    Consistent evidence indicates that exercise improves cognition and mood, with preliminary evidence suggesting that brain-derived neurotrophic factor (BDNF) may mediate these effects. The aim of the current meta-analysis was to provide an estimate of the strength of the association between exercise and increased BDNF levels in humans across multiple exercise paradigms. We conducted a meta-analysis of 29 studies (N = 1,111 participants) examining the effect of exercise on BDNF levels in three e...

  1. Human reliability under sleep deprivation: Derivation of performance shaping factor multipliers from empirical data

    International Nuclear Information System (INIS)

    Griffith, Candice D.; Mahadevan, Sankaran

    2015-01-01

    This paper develops a probabilistic approach that could use empirical data to derive values of performance shaping factor (PSF) multipliers for use in quantitative human reliability analysis (HRA). The proposed approach is illustrated with data on sleep deprivation effects on performance. A review of existing HRA methods reveals that sleep deprivation is not explicitly included at present, and expert opinion is frequently used to inform HRA model multipliers. In this paper, quantitative data from empirical studies regarding the effect of continuous hours of wakefulness on performance measures (reaction time, accuracy, and number of lapses) are used to develop a method to derive PSF multiplier values for sleep deprivation, in the context of the SPAR-H model. Data is extracted from the identified studies according to the meta-analysis research synthesis method and used to investigate performance trends and error probabilities. The error probabilities in test and control conditions are compared, and the resulting probability ratios are suggested for use in informing the selection of PSF multipliers in HRA methods. Although illustrated for sleep deprivation, the proposed methodology is general, and can be applied to other performance shaping factors. - Highlights: • Method proposed to derive performance shaping factor multipliers from empirical data. • Studies reporting the effect of sleep deprivation on performance are analyzed. • Test data using psychomotor vigilance tasks are analyzed. • Error probability multipliers computed for reaction time, lapses, and accuracy measures.

  2. Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells

    DEFF Research Database (Denmark)

    Secher, Jan Ole Bertelsen; Ceylan, Ahmet; Mazzoni, Gianluca

    2017-01-01

    Derivation and stable maintenance of porcine induced pluripotent stem cells (piPSCs) is challenging. We herein systematically analyzed two piPSC lines, derived by lentiviral transduction and cultured under either leukemia inhibitory factor (LIF) or fibroblast growth factor (FGF) conditions, to sh...

  3. LARGE-SCALE MAGNETIC HELICITY FLUXES ESTIMATED FROM MDI MAGNETIC SYNOPTIC CHARTS OVER THE SOLAR CYCLE 23

    International Nuclear Information System (INIS)

    Yang Shangbin; Zhang Hongqi

    2012-01-01

    To investigate the characteristics of large-scale and long-term evolution of magnetic helicity with solar cycles, we use the method of Local Correlation Tracking to estimate the magnetic helicity evolution over solar cycle 23 from 1996 to 2009 using 795 MDI magnetic synoptic charts. The main results are as follows: the hemispheric helicity rule still holds in general, i.e., the large-scale negative (positive) magnetic helicity dominates the northern (southern) hemisphere. However, the large-scale magnetic helicity fluxes show the same sign in both hemispheres around 2001 and 2005. The global, large-scale magnetic helicity flux over the solar disk changes from a negative value at the beginning of solar cycle 23 to a positive value at the end of the cycle, while the net accumulated magnetic helicity is negative in the period between 1996 and 2009.

  4. LARGE-SCALE MAGNETIC HELICITY FLUXES ESTIMATED FROM MDI MAGNETIC SYNOPTIC CHARTS OVER THE SOLAR CYCLE 23

    Energy Technology Data Exchange (ETDEWEB)

    Yang Shangbin; Zhang Hongqi, E-mail: yangshb@nao.cas.cn [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, 100012 Beijing (China)

    2012-10-10

    To investigate the characteristics of large-scale and long-term evolution of magnetic helicity with solar cycles, we use the method of Local Correlation Tracking to estimate the magnetic helicity evolution over solar cycle 23 from 1996 to 2009 using 795 MDI magnetic synoptic charts. The main results are as follows: the hemispheric helicity rule still holds in general, i.e., the large-scale negative (positive) magnetic helicity dominates the northern (southern) hemisphere. However, the large-scale magnetic helicity fluxes show the same sign in both hemispheres around 2001 and 2005. The global, large-scale magnetic helicity flux over the solar disk changes from a negative value at the beginning of solar cycle 23 to a positive value at the end of the cycle, while the net accumulated magnetic helicity is negative in the period between 1996 and 2009.

  5. Delineating pMDI model reactions with loblolly pine via solution-state NMR spectroscopy. Part 1, Catalyzed reactions with wood models and wood polymers

    Science.gov (United States)

    Daniel J. Yelle; John Ralph; Charles R. Frihart

    2011-01-01

    To better understand adhesive interactions with wood, reactions between model compounds of wood and a model compound of polymeric methylene diphenyl diisocyanate (pMDI) were characterized by solution-state NMR spectroscopy. For comparison, finely ground loblolly pine sapwood, milled-wood lignin and holocellulose from the same wood were isolated and derivatized with...

  6. Proportional-Integral-Derivative (PID) Control of Secreted Factors for Blood Stem Cell Culture.

    Science.gov (United States)

    Caldwell, Julia; Wang, Weijia; Zandstra, Peter W

    2015-01-01

    Clinical use of umbilical cord blood has typically been limited by the need to expand hematopoietic stem and progenitor cells (HSPC) ex vivo. This expansion is challenging due to the accumulation of secreted signaling factors in the culture that have a negative regulatory effect on HSPC output. Strategies for global regulation of these factors through dilution have been developed, but do not accommodate the dynamic nature or inherent variability of hematopoietic cell culture. We have developed a mathematical model to simulate the impact of feedback control on in vitro hematopoiesis, and used it to design a proportional-integral-derivative (PID) control algorithm. This algorithm was implemented with a fed-batch bioreactor to regulate the concentrations of secreted factors. Controlling the concentration of a key target factor, TGF-β1, through dilution limited the negative effect it had on HSPCs, and allowed global control of other similarly-produced inhibitory endogenous factors. The PID control algorithm effectively maintained the target soluble factor at the target concentration. We show that feedback controlled dilution is predicted to be a more cost effective dilution strategy compared to other open-loop strategies, and can enhance HSPC expansion in short term culture. This study demonstrates the utility of secreted factor process control strategies to optimize stem cell culture systems, and motivates the development of multi-analyte protein sensors to automate the manufacturing of cell therapies.

  7. Influence of storage conditions on the release of growth factors in platelet-rich blood derivatives

    Directory of Open Access Journals (Sweden)

    Düregger Katharina

    2016-09-01

    Full Text Available Thrombocytes can be concentrated in blood derivatives and used as autologous transplants e.g. for wound treatment due to the release of growth factors such as platelet derived growth factor (PDGF. Conditions for processing and storage of these platelet-rich blood derivatives influence the release of PDGF from the platelet-bound α-granules into the plasma. In this study Platelet rich plasma (PRP and Platelet concentrate (PC were produced with a fully automated centrifugation system. Storage of PRP and PC for 1 h up to 4 months at temperatures between −20°C and +37°C was applied with the aim of evaluating the influence on the amount of released PDGF. Storage at −20°C resulted in the highest release of PDGF in PRP and a time dependency was determined: prolonged storage up to 1 month in PRP and 10 days in PC increased the release of PDGF. Regardless of the storage conditions, the release of PDGF per platelet was higher in PC than in PRP.

  8. Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect.

    Science.gov (United States)

    Mathijssen, Natascha C J; Masereeuw, Rosalinde; Holme, Pal Andre; van Kraaij, Marian G J; Laros-van Gorkom, Britta A P; Peyvandi, Flora; van Heerde, Waander L

    2013-08-01

    Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. Ten factor VII deficient patients were treated with either recombinant activated (20 μg/kg) or plasma-derived (25 IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236 ml/kg; 175 ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206 ml/kg; 64 ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy

    DEFF Research Database (Denmark)

    Klein, Anders B; Jennum, Poul; Knudsen, Stine

    2013-01-01

    in hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesised......Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction...... that serum levels of these factors are altered in patients with narcolepsy compared to healthy controls without sleep disturbances. Polysomnography data was obtained and serum BDNF and NGF levels measured using ELISA, while hypocretin was measured using RIA. Serum BDNF levels were significantly higher...

  10. Fibroblast growth factor-2 stimulates adipogenic differentiation of human adipose-derived stem cells

    International Nuclear Information System (INIS)

    Kakudo, Natsuko; Shimotsuma, Ayuko; Kusumoto, Kenji

    2007-01-01

    Adipose-derived stem cells (ASCs) have demonstrated a capacity for differentiating into a variety of lineages, including bone, cartilage, or fat, depending on the inducing stimuli and specific growth and factors. It is acknowledged that fibroblast growth factor-2 (FGF-2) promotes chondrogenic and inhibits osteogenic differentiation of ASCs, but thorough investigations of its effects on adipogenic differentiation are lacking. In this study, we demonstrate at the cellular and molecular levels the effect of FGF-2 on adipogenic differentiation of ASCs, as induced by an adipogenic hormonal cocktail consisting of 3-isobutyl-1-methylxanthine (IBMX), dexamethasone, insulin, and indomethacin. FGF-2 significantly enhances the adipogenic differentiation of human ASCs. Furthermore, in cultures receiving FGF-2 before adipogenic induction, mRNA expression of peroxisome proliferator-activated receptor γ2 (PPARγ2), a key transcription factor in adipogenesis, was upregulated. The results of FGF-2 supplementation suggest the potential applications of FGF-2 and ASCs in adipose tissue regeneration

  11. Platelet-Rich Plasma Derived Growth Factors Contribute to Stem Cell Differentiation in Musculoskeletal Regeneration

    Directory of Open Access Journals (Sweden)

    Yun Qian

    2017-10-01

    Full Text Available Stem cell treatment and platelet-rich plasma (PRP therapy are two significant issues in regenerative medicine. Stem cells such as bone marrow mesenchymal stem cells, adipose-derived stem cells and periodontal ligament stem cells can be successfully applied in the field of tissue regeneration. PRP, a natural product isolated from whole blood, can secrete multiple growth factors (GFs for regulating physiological activities. These GFs can stimulate proliferation and differentiation of different stem cells in injury models. Therefore, combination of both agents receives wide expectations in regenerative medicine, especially in bone, cartilage and tendon repair. In this review, we thoroughly discussed the interaction and underlying mechanisms of PRP derived GFs with stem cells, and assessed their functions in cell differentiation for musculoskeletal regeneration.

  12. Adhesion of nitrile rubber (NBR) to polyethylene terephthalate (PET) fabric. Part 1: PET surface modification by methylenediphenyl di-isocyanate (MDI)

    International Nuclear Information System (INIS)

    Razavizadeh, Mahmoud; Jamshidi, Masoud

    2016-01-01

    Graphical abstract: - Highlights: • Glutaric anhydride peroxide (GAP) was grafted on PET surface by UV irradiation method. Then MDI was attached to GAP on PET surface. • The fabric was vulcanized by nitrile rubber. • Peet test was performed after each stage of surface modification. • Curing temperature was increased and the tests were repeated. • Effect of MDI coating on PET without carboxylation was evaluated. Effect of vulcanizing temperature on this product was also studied. - Abstract: Fiber to rubber adhesion is an important subject in rubber composite industry. It is well known that surface physical, mechanical and chemical treatments are effective methods to improve interfacial bonding. Ultra violet (UV) light irradiation is an efficient method which is used to increase interfacial interactions. In this research UV assisted chemical modification of PET fabric was used to increase its bonding to nitrile rubber (NBR). NBR is perfect selection to produce fuel and oil resistant rubber parts but it has weak bonding to fabrics. For this purpose at first, the PET fabric was carboxylated under UV irradiation and then methylenediphenyl diisocyanate (MDI) was reacted and grafted to carboxylated PET. T-peel test was used to evaluate PET fabric to NBR bonding strength. Attenuated total reflectance-Fourier transform infrared spectroscopy (FTIR-AT) was used to assess surface modifications of the PET fabrics. The chemical composition of the PET surfaces before and after carboxylation and MDI grafting was investigated by X-ray photoelectron spectroscopy (XPS). It was found that at vulcanizing temperature of 150 °C, carboxylation in contrary to MDI grafting, improved considerably PET to NBR adhesion. Finally effect of curing temperature on PET to NBR bonding strength was determined. It was found that increasing vulcanizing temperature to 170 °C caused considerable improvement (about 134%) in bonding strength.

  13. More inflammation but less brain-derived neurotrophic factor in antisocial personality disorder.

    Science.gov (United States)

    Wang, Tzu-Yun; Lee, Sheng-Yu; Hu, Ming-Chuan; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chu, Chun-Hsien; Lin, Shih-Hsien; Li, Chia-Ling; Wang, Liang-Jen; Chen, Po See; Chen, Shih-Heng; Huang, San-Yuan; Tzeng, Nian-Sheng; Lee, I Hui; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

    2017-11-01

    Antisocial personality disorder (ASPD) is highly comorbid with substance use disorders (SUDs). We hypothesize that chronic neuroinflammation and the loss of neurotrophic factors prompts the pathogenesis of both disorders. We used ELISA to measure plasma levels of proinflammatory (tumor necrosis factor-α [TNF-α], C-reactive protein [CRP]) and anti-inflammatory factors (transforming growth factor-β1 [TGF-β1] and interleukin-10 [IL-10]), and brain-derived neurotrophic factor (BDNF) in male patients with ASPD (n=74), SUDs (n=168), ASPD comorbid with SUDs (ASPD+SUDs) (n=438), and Healthy Controls (HCs) (n=81). A multivariate analysis of covariance (MANCOVA) controlled for possible confounders was used to compare cytokines and BDNF levels between groups. The results of MANCOVA adjusted for age showed a significant (pdisorder (OUD) and other SUDs groups showed that the IL-10 levels were specifically higher in OUD and ASPD±OUD groups than other SUDs (P≤0.001). We conclude that uncontrolled inflammation and losing neurotrophic factors, with or without comorbid SUDs, underlies ASPD. IL-10 expression might be more specifically associated with OUD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Stage specific requirement of platelet-derived growth factor receptor-α in embryonic development.

    Directory of Open Access Journals (Sweden)

    Chen Qian

    Full Text Available Platelet-derived growth factor receptor alpha (PDGFRα is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures.To address the temporal requirement of Pdgfra in embryonic development.We have deleted the Pdgfra in Pdgfra-expressing tissues at different embryonic stages in mice, examined and quantified the developmental anomalies.Current study showed that (i conditional deletion of Pdgfra at different embryonic days (between E7.5 and E10.5 resulted in orofacial cleft, spina bifida, rib cage deformities, and omphalocele, and (ii the day of Pdgfra deletion influenced the combinations, incidence and severities of these anomalies. Deletion of Pdgfra caused apoptosis of Pdgfra-expressing tissues, and developmental defects of their derivatives.Orofacial cleft, spina bifida and omphalocele are among the commonest skeletal and abdominal wall defects of newborns, but their genetic etiologies are largely unknown. The remarkable resemblance of our conditional Pdgfra knockout embryos to theses human congenital anomalies, suggesting that dysregulated PDGFRA expression could cause these anomalies in human. Future work should aim at defining (a the regulatory elements for the expression of the human PDGFRA during embryonic development, and (b if mutations / sequence variations of these regulatory elements cause these anomalies.

  15. Breaking the mold: transcription factors in the anucleate platelet and platelet-derived microparticles

    Directory of Open Access Journals (Sweden)

    Katie L Lannan

    2015-02-01

    Full Text Available Platelets are small anucleate blood cells derived from megakaryocytes. In addition to their pivotal roles in hemostasis, platelets are the smallest, yet most abundant, immune cell and regulate inflammation, immunity, and disease progression. Although platelets lack DNA, and thus no functional transcriptional activities, they are nonetheless rich sources of RNAs, possess an intact spliceosome, and are thus capable of synthesizing proteins. Previously, it was thought that platelet RNAs and translational machinery were remnants from the megakaryocyte. We now know that the initial description of platelets as cellular fragments is an antiquated notion, as mounting evidence suggests otherwise. Therefore, it is reasonable to hypothesize that platelet transcription factors are not vestigial remnants from megakaryoctes, but have important, if only partly understood functions. Proteins play multiple cellular roles to minimize energy expenditure for maximum cellular function; thus, the same can be expected for transcription factors. In fact, numerous transcription factors have non-genomic roles, both in platelets and in nucleated cells. Our lab and others have discovered the presence and nongenomic roles of transcription factors in platelets, such as the nuclear factor kappa β (NFκB family of proteins and peroxisome proliferator activated receptor gamma (PPARγ. In addition to numerous roles in regulating platelet activation, functional transcription factors can be transferred to vascular and immune cells through platelet microparticles. This method of transcellular delivery of key immune molecules may be a vital mechanism by which platelet transcription factors regulate inflammation and immunity. At the very least, platelets are an ideal model cell to dissect out the nongenomic roles of transcription factors in nucleated cells. There is abundant evidence to suggest that transcription factors in platelets play key roles in regulating inflammatory and

  16. Are genetic variants in the platelet-derived growth factor [beta] gene associated with chronic pancreatitis?

    Science.gov (United States)

    Muddana, Venkata; Park, James; Lamb, Janette; Yadav, Dhiraj; Papachristou, Georgios I; Hawes, Robert H; Brand, Randall; Slivka, Adam; Whitcomb, David C

    2010-11-01

    Platelet-derived growth factor [beta] (PDGF-[beta]) is a major signal in proliferation and matrix synthesis through activated pancreatic stellate cells, leading to fibrosis of the pancreas. Recurrent acute pancreatitis (RAP) seems to predispose to chronic pancreatitis (CP) in some patients but not others. We tested the hypothesis that 2 known PDGF-[beta] polymorphisms are associated with progression from RAP to CP. We also tested the hypothesis that PDGF-[beta] polymorphisms in combination with environmental risk factors such as alcohol and smoking are associated with CP. Three hundred eighty-two patients with CP (n = 176) and RAP (n = 206) and 251 controls were evaluated. Platelet-derived growth factor [beta] polymorphisms +286 A/G (rs#1800818) seen in 5'-UTR and +1135 A/C (rs#1800817) in first intron were genotyped using single-nucleotide polymorphism polymerase chain reaction approach and confirmed by DNA sequencing. The genotypic frequencies for PDGF-[beta] polymorphisms in positions +286 and +1135 were found to be similar in controls and patients with RAP and CP. There was no difference in genotypic frequencies among RAP, CP, and controls in subjects in the alcohol and smoking subgroups. Known variations in the PDGF-[beta] gene do not have a significant effect on promoting or preventing fibrogenesis in pancreatitis. Further evaluation of this important pathway is warranted.

  17. Nerve growth factor, brain-derived neurotrophic factor, and the chronobiology of mood: a new insight into the "neurotrophic hypothesis"

    Directory of Open Access Journals (Sweden)

    Tirassa P

    2015-10-01

    Full Text Available Paola Tirassa,1 Adele Quartini,2 Angela Iannitelli2–4 1National Research Council (CNR, Institute of Cell Biology and Neurobiology (IBCN, 2Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine – "Sapienza" University of Rome, 3Italian Psychoanalytical Society (SPI, Rome, Italy; 4International Psychoanalytical Association (IPA, London, UKAbstract: The light information pathways and their relationship with the body rhythms have generated a new insight into the neurobiology and the neurobehavioral sciences, as well as into the clinical approaches to human diseases associated with disruption of circadian cycles. Light-based strategies and/or drugs acting on the circadian rhythms have widely been used in psychiatric patients characterized by mood-related disorders, but the timing and dosage use of the various treatments, although based on international guidelines, are mainly dependent on the psychiatric experiences. Further, many efforts have been made to identify biomarkers able to disclose the circadian-related aspect of diseases, and therefore serve as diagnostic, prognostic, and therapeutic tools in clinic to assess the different mood-related symptoms, including pain, fatigue, sleep disturbance, loss of interest or pleasure, appetite, psychomotor changes, and cognitive impairments. Among the endogenous factors suggested to be involved in mood regulation, the neurotrophins, nerve growth factor, and brain-derived neurotrophic factor show anatomical and functional link with the circadian system and mediate some of light-induced effects in brain. In addition, in humans, both nerve growth factor and brain-derived neurotrophic factor have showed a daily rhythm, which correlate with the morningness–eveningness dimensions, and are influenced by light, suggesting their potential role as biomarkers for chronotypes and/or chronotherapy. The evidences of the relationship between the diverse mood-related disorders

  18. Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course

    DEFF Research Database (Denmark)

    Mansur, Rodrigo B; Santos, Camila M; Rizzo, Lucas B

    2016-01-01

    OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism......, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (Psuicide attempts (P=.021). IGM moderated...... the association between BDNF and the number of previous mood episodes (P

  19. Association of coatomer proteins with the beta-receptor for platelet-derived growth factor

    DEFF Research Database (Denmark)

    Hansen, Klaus; Rönnstrand, L; Rorsman, C

    1997-01-01

    The nonreceptor tyrosine kinase Src binds to and is activated by the beta-receptor for platelet-derived growth factor (PDGF). The interaction leads to Src phosphorylation of Tyr934 in the kinase domain of the receptor. In the course of the functional characterization of this phosphorylation, we...... of intracellular vesicle transport. In order to explore the functional significance of the interaction between alpha- and beta'-COP and the PDGF receptor, a receptor mutant was made in which the conserved histidine residue 928 was mutated to an alanine residue. The mutant receptor, which was unable to bind alpha...

  20. Molecular mechanisms underlying the regulation of brain-derived neurotrophic factor (BDNF) translation in dendrites

    OpenAIRE

    Pinheiro, Vera Lúcia Margarido

    2010-01-01

    Dissertação de mestrado em Biologia Celular e Molecular apresentada ao Departamento de Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra A especificidade espacial e temporal subjacente à diversidade de processos de plasticidade sináptica que ocorrem no sistema nervoso central está profundamente relacionada com a disponibilidade da proteína brain-derived neurotrophic factor (BDNF) em domínios sub-celulares distintos, especialmente na área pós-sinápti...

  1. The study on transport of brain-derived neurotrophic factor in facial nerve

    International Nuclear Information System (INIS)

    Li Yunchun; Li Lin; Wang Quanlin; Yang Xiaochuan; He Gang; Gao Bingqing; Lin Daicheng; Liang Chuanyu

    2000-01-01

    The transport information of brain-derived neurotrophic factor (BDNF) in facial nerve is studied using 125 I-BDNF or 131 I-BDNF. After one lateral facial nerve trunk of adult rabbit is transected, a silicone chamber is inserted between the stumps, and labelled compounds are administered into the chamber. Bilateral facial nerve trunk and facial nerve motor neurone of brain-stem of rabbits are collected and counted respectively, and imaged at coronary position of head in live rabbit. The results show that BDNF has a retrograde transport in facial nerve, and the transport of 131 I-BDNF is marked restrained by BDNF in facial nerve

  2. Derived concentration factors for caesium-137 in edible species of North Sea fish

    International Nuclear Information System (INIS)

    Steele, A.K.

    1990-01-01

    Concentration factor (CF=Bq kg -1 fillet/Bg kg -1 filtered sea water) values for 137 Cs in fillets of cod (Gadus morhua), haddock (Merlanogrammus aeglefinus), plaice (Pleuronectes platessa) and whiting (Merlangius merlangius), were derived from fish and filtered seawater concentrations. Samples were collected in twelve sampling boxes in the North Sea over an eight-year period - 1978-1985. The range of results with species, between species, and between surveys are discussed. Mean CF values of 92, 58, 39 and 150 were found in cod, haddock, plaice and whiting respectively. These support the International Atomic Energy Authority recommended CF value of 100 for fish in generalised dose assessments. (author)

  3. Cytokines, brain-derived neurotrophic factor and C-reactive protein in bipolar I disorder

    DEFF Research Database (Denmark)

    Jacoby, Anne Sophie; Munkholm, Klaus; Vinberg, Maj

    2016-01-01

    BACKGROUND: Peripheral blood brain-derived neurotrophic factor (BDNF) and inflammatory markers may reflect key pathophysiological mechanisms in bipolar disorder in relation to disease activity and neuroprogression. AIMS: To investigate whether neutrophins and inflammatory marker vary with mood...... overall compared with healthy control subjects. However, in adjusted models, no statistically significant differences were found in any measure between patients and control individuals. Levels of hsCRP in depressive states were decreased with 40% (95% CI: 5-62%, p=0.029) compared with euthymia and with 48...

  4. Empirical Derivation of Correction Factors for Human Spiral Ganglion Cell Nucleus and Nucleolus Count Units.

    Science.gov (United States)

    Robert, Mark E; Linthicum, Fred H

    2016-01-01

    Profile count method for estimating cell number in sectioned tissue applies a correction factor for double count (resulting from transection during sectioning) of count units selected to represent the cell. For human spiral ganglion cell counts, we attempted to address apparent confusion between published correction factors for nucleus and nucleolus count units that are identical despite the role of count unit diameter in a commonly used correction factor formula. We examined a portion of human cochlea to empirically derive correction factors for the 2 count units, using 3-dimensional reconstruction software to identify double counts. The Neurotology and House Histological Temporal Bone Laboratory at University of California at Los Angeles. Using a fully sectioned and stained human temporal bone, we identified and generated digital images of sections of the modiolar region of the lower first turn of cochlea, identified count units with a light microscope, labeled them on corresponding digital sections, and used 3-dimensional reconstruction software to identify double-counted count units. For 25 consecutive sections, we determined that double-count correction factors for nucleus count unit (0.91) and nucleolus count unit (0.92) matched the published factors. We discovered that nuclei and, therefore, spiral ganglion cells were undercounted by 6.3% when using nucleolus count units. We determined that correction factors for count units must include an element for undercounting spiral ganglion cells as well as the double-count element. We recommend a correction factor of 0.91 for the nucleus count unit and 0.98 for the nucleolus count unit when using 20-µm sections. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  5. Distinctive diet-tissue isotopic discrimination factors derived from the exclusive bamboo-eating giant panda.

    Science.gov (United States)

    Han, Han; Wei, Wei; Nie, Yonggang; Zhou, Wenliang; Hu, Yibo; Wu, Qi; Wei, Fuwen

    2016-11-01

    Stable isotope analysis is very useful in animal ecology, especially in diet reconstruction and trophic studies. Differences in isotope ratios between consumers and their diet, termed discrimination factors, are essential for studies of stable isotope ecology and are species-specific and tissue-specific. Given the specialized bamboo diet and clear foraging behavior, here, we calculated discrimination factors for carbon and nitrogen isotopes from diet to tissues (tooth enamel, hair keratin and bone collagen) for the giant panda (Ailuropoda melanoleuca), a species derived from meat-eating ancestors. Our results showed that carbon discrimination factor obtained from giant panda tooth enamel (ε 13 C diet-enamel = 10.0‰) and nitrogen discrimination factors from hair keratin (Δ 15 N diet-hair = 2.2‰) and bone collagen (Δ 15 N diet-collagen = 2.3‰) were lower, and carbon discrimination factors from hair keratin (Δ 13 C diet-hair = 5.0‰) and bone collagen (Δ 13 C diet-collagen = 6.1‰) were higher than those of other mammalian carnivores, omnivores and herbivores. Such distinctive values are likely the result of a low-nutrient and specialized bamboo diet, carnivore-like digestive system and exceptionally low metabolism in giant pandas. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  6. Covalent immobilization of stem cell factor and stromal derived factor 1α for in vitro culture of hematopoietic progenitor cells.

    Science.gov (United States)

    Cuchiara, Maude L; Horter, Kelsey L; Banda, Omar A; West, Jennifer L

    2013-12-01

    Hematopoietic stem cells (HSCs) are currently utilized in the treatment of blood diseases, but widespread application of HSC therapeutics has been hindered by the limited availability of HSCs. With a better understanding of the HSC microenvironment and the ability to precisely recapitulate its components, we may be able to gain control of HSC behavior. In this work we developed a novel, biomimetic PEG hydrogel material as a substrate for this purpose and tested its potential with an anchorage-independent hematopoietic cell line, 32D clone 3 cells. We immobilized a fibronectin-derived adhesive peptide sequence, RGDS; a cytokine critical in HSC self-renewal, stem cell factor (SCF); and a chemokine important in HSC homing and lodging, stromal derived factor 1α (SDF1α), onto the surfaces of poly(ethylene glycol) (PEG) hydrogels. To evaluate the system's capabilities, we observed the effects of the biomolecules on 32D cell adhesion and morphology. We demonstrated that the incorporation of RGDS onto the surfaces promotes 32D cell adhesion in a dose-dependent fashion. We also observed an additive response in adhesion on surfaces with RGDS in combination with either SCF or SDF1α. In addition, the average cell area increased and circularity decreased on gel surfaces containing immobilized SCF or SDF1α, indicating enhanced cell spreading. By recapitulating aspects of the HSC microenvironment using a PEG hydrogel scaffold, we have shown the ability to control the adhesion and spreading of the 32D cells and demonstrated the potential of the system for the culture of primary hematopoietic cell populations. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  7. Platelet-derived growth factor-C and -D in the cardiovascular system and diseases.

    Science.gov (United States)

    Lee, Chunsik; Li, Xuri

    2018-08-01

    The cardiovascular system is among the first organs formed during development and is pivotal for the formation and function of the rest of the organs and tissues. Therefore, the function and homeostasis of the cardiovascular system are finely regulated by many important molecules. Extensive studies have shown that platelet-derived growth factors (PDGFs) and their receptors are critical regulators of the cardiovascular system. Even though PDGF-C and PDGF-D are relatively new members of the PDGF family, their critical roles in the cardiovascular system as angiogenic and survival factors have been amply demonstrated. Understanding the functions of PDGF-C and PDGF-D and the signaling pathways involved may provide novel insights into both basic biomedical research and new therapeutic possibilities for the treatment of cardiovascular diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. A new FACS approach isolates hESC derived endoderm using transcription factors.

    Directory of Open Access Journals (Sweden)

    Yuqiong Pan

    2011-03-01

    Full Text Available We show that high quality microarray gene expression profiles can be obtained following FACS sorting of cells using combinations of transcription factors. We use this transcription factor FACS (tfFACS methodology to perform a genomic analysis of hESC-derived endodermal lineages marked by combinations of SOX17, GATA4, and CXCR4, and find that triple positive cells have a much stronger definitive endoderm signature than other combinations of these markers. Additionally, SOX17(+ GATA4(+ cells can be obtained at a much earlier stage of differentiation, prior to expression of CXCR4(+ cells, providing an important new tool to isolate this earlier definitive endoderm subtype. Overall, tfFACS represents an advancement in FACS technology which broadly crosses multiple disciplines, most notably in regenerative medicine to redefine cellular populations.

  9. Derivation of the mass factors for decommissioning cost estimation of low contaminated auxiliary systems

    International Nuclear Information System (INIS)

    Poskas, G.

    2015-01-01

    Ignalina NPP was operating two RBMK-1500 reactors. Unit 1 was closed at the end of 2004, and Unit 2 - at the end of 2009. Now they are under decommissioning. Decommissioning has been started from the reactor's periphery, with dismantling of non-contaminated and low contaminated equipment and installations. This paper discusses a methodology for derivation of mass factors for preliminary decommissioning costing at NPP when the number of inventory items is significant, and separate consideration of each inventory item is impossible or impractical for preliminary decommissioning plan, especially when the level of radioactive contamination is very low. The methodology is based on detailed data analysis of building V1 taking into account period and inventory based activities, investment and consumables and other decommissioning approach- related properties for building average mass factors. The methodology can be used for cost estimation of preliminary decommissioning planning of NPP auxiliary buildings with mostly very low level contamination. (authors)

  10. Downregulated Brain-Derived Neurotrophic Factor-Induced Oxidative Stress in the Pathophysiology of Diabetic Retinopathy.

    Science.gov (United States)

    Behl, Tapan; Kotwani, Anita

    2017-04-01

    Brain-derived neurotrophic factor (BDNF), a member of neurotrophin growth factor family, physiologically mediates induction of neurogenesis and neuronal differentiation, promotes neuronal growth and survival and maintains synaptic plasticity and neuronal interconnections. Unlike the central nervous system, its secretion in the peripheral nervous system occurs in an activity-dependent manner. BDNF improves neuronal mortality, growth, differentiation and maintenance. It also provides neuroprotection against several noxious stimuli, thereby preventing neuronal damage during pathologic conditions. However, in diabetic retinopathy (a neuromicrovascular disorder involving immense neuronal degeneration), BDNF fails to provide enough neuroprotection against oxidative stress-induced retinal neuronal apoptosis. This review describes the prime reasons for the downregulation of BDNF-mediated neuroprotective actions during hyperglycemia, which renders retinal neurons vulnerable to damaging stimuli, leading to diabetic retinopathy. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  11. Role of Stress-Related Brain-Derived Neurotrophic Factor (BDNF) in the Rat Submandibular Gland

    International Nuclear Information System (INIS)

    Tsukinoki, Keiichi; Saruta, Juri

    2012-01-01

    The nerve growth factor (NGF) family comprises NGF, brain-derived neurotrophic factor (BDNF) and neurotrophins (NTs)-3, -4/5, -6 and -7, all of which are collectively referred to as neurotrophins. However, the expression of neurotrophins other than NGF in the salivary gland has not been described in detail. Through interaction with the TrkB receptor, BDNF plays an important role in long-term potentiation. We found that BDNF expression increased within submandibular gland tissue in response to stress, suggesting that the salivary glands are sensitive to stress. In addition, stress caused increases in plasma BDNF derived from the submandibular gland and in TrkB receptor mRNA in the adrenal medulla. Plasma BDNF might activate TrkB receptors in the adrenal medulla during acute stress. The salivary glands are likely to influence not only oral health, but also systemic organs. This review addressed the relationship between hormone-like effects and stress-related BDNF expression in the rat submandibular gland

  12. Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells.

    Science.gov (United States)

    Kemp, Kevin; Dey, Rimi; Cook, Amelia; Scolding, Neil; Wilkins, Alastair

    2017-08-01

    Friedreich's ataxia is an inherited neurological disorder characterised by mitochondrial dysfunction and increased susceptibility to oxidative stress. At present, no therapy has been shown to reduce disease progression. Strategies being trialled to treat Friedreich's ataxia include drugs that improve mitochondrial function and reduce oxidative injury. In addition, stem cells have been investigated as a potential therapeutic approach. We have used siRNA-induced knockdown of frataxin in SH-SY5Y cells as an in vitro cellular model for Friedreich's ataxia. Knockdown of frataxin protein expression to levels detected in patients with the disorder was achieved, leading to decreased cellular viability, increased susceptibility to hydrogen peroxide-induced oxidative stress, dysregulation of key anti-oxidant molecules and deficiencies in both cell proliferation and differentiation. Bone marrow stem cells are being investigated extensively as potential treatments for a wide range of neurological disorders, including Friedreich's ataxia. The potential neuroprotective effects of bone marrow-derived mesenchymal stem cells were therefore studied using our frataxin-deficient cell model. Soluble factors secreted by mesenchymal stem cells protected against cellular changes induced by frataxin deficiency, leading to restoration in frataxin levels and anti-oxidant defences, improved survival against oxidative stress and stimulated both cell proliferation and differentiation down the Schwann cell lineage. The demonstration that mesenchymal stem cell-derived factors can restore cellular homeostasis and function to frataxin-deficient cells further suggests that they may have potential therapeutic benefits for patients with Friedreich's ataxia.

  13. Abnormal platelet-derived growth factor signaling accounting for lung hypoplasia in experimental congenital diaphragmatic hernia.

    Science.gov (United States)

    Dingemann, Jens; Doi, Takashi; Ruttenstock, Elke; Puri, Prem

    2010-10-01

    The pathogenesis of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) is not fully understood. Platelet-derived growth factor A (PDGFA) and platelet-derived growth factor receptor α (PDGFRα) play a crucial role in lung development. It has been reported that PDGF induces H(2)O(2)-production and that oxidative stress may be an important mechanism for the impaired lung development in the nitrofen rat model. We hypothesized that pulmonary expression of PDGFA and PDGFRα is altered in the nitrofen induced CDH model. Pregnant rats received 100 mg nitrofen or vehicle on gestational day 9 (D9) and were sacrificed on D15, D18 or D21. RNA was extracted from fetal left lungs and mRNA levels of PDGFA and PDGFRα were determined using real-time polymerase chain reaction. Immunohistochemistry for protein expression of PDGFA and PDGFRα was performed. Pulmonary H(2)O(2) was measured colorimetrically. mRNA levels of PDGFRα at D15 (4.50 ± 0.87) and PDGFA at D18 (2.90 ± 1.38) were increased in the nitrofen group (P stress during lung development. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Principal component analysis for predicting transcription-factor binding motifs from array-derived data

    Directory of Open Access Journals (Sweden)

    Vincenti Matthew P

    2005-11-01

    Full Text Available Abstract Background The responses to interleukin 1 (IL-1 in human chondrocytes constitute a complex regulatory mechanism, where multiple transcription factors interact combinatorially to transcription-factor binding motifs (TFBMs. In order to select a critical set of TFBMs from genomic DNA information and an array-derived data, an efficient algorithm to solve a combinatorial optimization problem is required. Although computational approaches based on evolutionary algorithms are commonly employed, an analytical algorithm would be useful to predict TFBMs at nearly no computational cost and evaluate varying modelling conditions. Singular value decomposition (SVD is a powerful method to derive primary components of a given matrix. Applying SVD to a promoter matrix defined from regulatory DNA sequences, we derived a novel method to predict the critical set of TFBMs. Results The promoter matrix was defined to establish a quantitative relationship between the IL-1-driven mRNA alteration and genomic DNA sequences of the IL-1 responsive genes. The matrix was decomposed with SVD, and the effects of 8 potential TFBMs (5'-CAGGC-3', 5'-CGCCC-3', 5'-CCGCC-3', 5'-ATGGG-3', 5'-GGGAA-3', 5'-CGTCC-3', 5'-AAAGG-3', and 5'-ACCCA-3' were predicted from a pool of 512 random DNA sequences. The prediction included matches to the core binding motifs of biologically known TFBMs such as AP2, SP1, EGR1, KROX, GC-BOX, ABI4, ETF, E2F, SRF, STAT, IK-1, PPARγ, STAF, ROAZ, and NFκB, and their significance was evaluated numerically using Monte Carlo simulation and genetic algorithm. Conclusion The described SVD-based prediction is an analytical method to provide a set of potential TFBMs involved in transcriptional regulation. The results would be useful to evaluate analytically a contribution of individual DNA sequences.

  15. [Risk factors associated with bacterial growth in derivative systems from cerebrospinal liquid in pediatric patients].

    Science.gov (United States)

    de Jesús Vargas-Lares, José; Andrade-Aguilera, Angélica Rocío; Díaz-Peña, Rafael; Barrera de León, Juan Carlos

    2015-01-01

    To determine risk factors associated with bacterial growth in systems derived from cerebrospinal fluid in pediatric patients. Case and controls study from January to December 2012, in patients aged <16 years who were carriers of hydrocephalus and who required placement or replacement of derivative system. Cases were considered as children with cultures with bacterial growth and controls with negative bacterial growth. Inferential statistics with Chi-squared and Mann-Whitney U tests. Association of risk with odds ratio. We reviewed 746 registries, cases n=99 (13%) and controls n=647 (87%). Masculine gender 58 (57%) vs. feminine gender 297 (46%) (p=0.530). Age of cases: median, five months and controls, one year (p=0.02). Median weight, 7 vs. 10 kg (p=0.634). Surgical interventions: median n=2 (range, 1-8) vs. n=1 (range, 1-7). Infection rate, 13.2%. Main etiology ductal stenosis, n=29 (29%) vs. n=50 (23%) (p=0.530). Non-communicating, n=50 (51%) vs. 396 (61%) (p=0.456). Predominant microorganisms: enterobacteria, pseudomonas, and enterococcus. Non-use of iodized dressing OR=2.6 (range, 1.8-4.3), use of connector OR=6.8 (range, 1.9-24.0), System replacement OR=2.0 (range, 1.3-3.1), assistant without surgical facemask OR=9.7 (range, 2.3-42.0). Being a breastfeeding infant, of low weight, non-application of iodized dressing, use of connector, previous derivation, and lack of adherence to aseptic technique were all factors associated with ependymitis.

  16. Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect

    NARCIS (Netherlands)

    Mathijssen, N.C.J.; Masereeuw, R.; Holme, P.A.; Kraaij, M.G.J. van; Laros, B.A.P.; Peyvandi, F.; Heerde, W.L. van

    2013-01-01

    INTRODUCTION: Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. MATERIALS AND METHODS: Ten factor VII deficient patients

  17. Statistic derivation of Taylor factors for polycrystalline metals with application to pure magnesium

    International Nuclear Information System (INIS)

    Shen, J.H.; Li, Y.L.; Wei, Q.

    2013-01-01

    We have investigated the Taylor factors of textured as well as texture-free polycrystalline aggregates. We begin with examining the Schmid factors of single crystals. A statistical model is then introduced to describe the distribution of grain orientations as well as the Schmid factor of individual grains of the polycrystalline system. The grains are classified into “soft” and “hard” ones. Based on this, a model is proposed for the derivation of the Taylor factors of textured as well as texture-free polycrystalline metals, and as a case study it is applied to polycrystalline magnesium. The model predictions are in very good agreement with the available experimental results. No free parameters have been involved in the development of this model, and the physical processes are clearly defined. Based on the fundamental assumption that grains can be classified into “soft” and “hard” in metals, this model should also be applicable to other hexagonal close packed metals such as α-titanium, beryllium and zirconium, as well as metals of other lattice structures such as face-centered cubic and body-centered cubic. It will also be interesting to see if this model can be incorporated into existing crystal plasticity models for the prediction of texture evolution under mechanical loading

  18. Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus.

    Science.gov (United States)

    Angelucci, Francesco; Ricci, Enzo; Padua, Luca; Sabino, Andrea; Tonali, Pietro Attilio

    2007-12-18

    It has been reported that music may have physiological effects on blood pressure, cardiac heartbeat, respiration, and improve mood state in people affected by anxiety, depression and other psychiatric disorders. However, the physiological bases of these phenomena are not clear. Hypothalamus is a brain region involved in the regulation of body homeostasis and in the pathophysiology of anxiety and depression through the modulation of hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic functions are also influenced by the presence of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are proteins involved in the growth, survival and function of neurons in the central nervous system. The aim of this study was to investigate the effect of music exposure in mice on hypothalamic levels of BDNF and NGF. We exposed young adult mice to slow rhythm music (6h per day; mild sound pressure levels, between 50 and 60 dB) for 21 consecutive days. At the end of the treatment mice were sacrificed and BDNF and NGF levels in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA). We found that music exposure significantly enhanced BDNF levels in the hypothalamus. Furthermore, we observed that music-exposed mice had decreased NGF hypothalamic levels. Our results demonstrate that exposure to music in mice can influence neurotrophin production in the hypothalamus. Our findings also suggest that physiological effects of music might be in part mediated by modulation of neurotrophins.

  19. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

    Directory of Open Access Journals (Sweden)

    A. Zembron-Lacny

    2016-01-01

    Full Text Available Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF and its relationship to oxidative damage and conventional cardiovascular disease (CVD biomarkers, such as atherogenic index, C-reactive protein (hsCRP and oxidized LDL (oxLDL, in active and inactive men. Seventeen elderly males (61-80 years and 17 young males (20-24 years participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001. In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL, hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men.

  20. Stromal cell-derived factor-1 alpha (SDF-1 alpha) improves neural recovery after spinal cord contusion in rats

    NARCIS (Netherlands)

    Zendedel, A.; Nobakht, M.; Bakhtiyari, M.; Beyer, C.; Kipp, M.; Baazm, M.; Joghataie, M.T.

    2012-01-01

    Stromal cell-derived factor-1 alpha (SDF-1α) is an important cytokine, implicated in the control of stem cell trafficking and bone marrow-derived stem cell mobilization. Generally, SDF-1α regulates multiple physiological processes such as embryonic development and organ homeostasis. There is also

  1. Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1

    Directory of Open Access Journals (Sweden)

    Shin-ichi Kawaguchi

    2018-04-01

    Full Text Available Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1 has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2c cells by measuring HIF response element (HRE promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity.

  2. Platelet-derived growth factor predicts prolonged relapse-free period in multiple sclerosis.

    Science.gov (United States)

    Stampanoni Bassi, Mario; Iezzi, Ennio; Marfia, Girolama A; Simonelli, Ilaria; Musella, Alessandra; Mandolesi, Georgia; Fresegna, Diego; Pasqualetti, Patrizio; Furlan, Roberto; Finardi, Annamaria; Mataluni, Giorgia; Landi, Doriana; Gilio, Luana; Centonze, Diego; Buttari, Fabio

    2018-04-14

    In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expression of brain damage producing enduring enhancement of synaptic strength largely dependent on neurotrophin-induced protein synthesis. Cytokines released by the immune cells during acute inflammation can alter synaptic transmission and plasticity possibly influencing the clinical course of MS. In addition, immune cells may promote brain repair during the post-acute phases, by secreting different growth factors involved in neuronal and oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a neurotrophic factor that could be particularly involved in clinical recovery. Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in MS and could therefore represent a key factor improving the clinical compensation of new brain lesions. The aim of the present study is to explore whether cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may influence the clinical course of RR-MS. At the time of diagnosis, we measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of the main pro- and anti-inflammatory cytokines, and of reliable markers of neuronal damage. Clinical and radiological parameters of disease activity were prospectively collected during follow-up. CSF PDGF levels were positively correlated with prolonged relapse-free survival. Radiological markers of disease activity, biochemical markers of neuronal damage, and clinical parameters of disease progression were instead not influenced by PDGF concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory milieu within the central nervous system. Our results suggest that PDGF could promote a

  3. Correlates of early pregnancy serum brain-derived neurotrophic factor in a Peruvian population.

    Science.gov (United States)

    Yang, Na; Levey, Elizabeth; Gelaye, Bizu; Zhong, Qiu-Yue; Rondon, Marta B; Sanchez, Sixto E; Williams, Michelle A

    2017-12-01

    Knowledge about factors that influence serum brain-derived neurotrophic factor (BDNF) concentrations during early pregnancy is lacking. The aim of the study is to examine the correlates of early pregnancy serum BDNF concentrations. A total of 982 women attending prenatal care clinics in Lima, Peru, were recruited in early pregnancy. Pearson's correlation coefficient was calculated to evaluate the relation between BDNF concentrations and continuous covariates. Analysis of variance and generalized linear models were used to compare the unadjusted and adjusted BDNF concentrations according to categorical variables. Multivariable linear regression models were applied to determine the factors that influence early pregnancy serum BDNF concentrations. In bivariate analysis, early pregnancy serum BDNF concentrations were positively associated with maternal age (r = 0.16, P BDNF concentrations. Participants with moderate antepartum depressive symptoms (Patient Health Questionnaire-9 (PHQ-9) score ≥ 10) had lower serum BDNF concentrations compared with participants with no/mild antepartum depressive symptoms (PHQ-9 score BDNF concentrations in low-income Peruvian women. Biological changes of CRP during pregnancy may affect serum BDNF concentrations.

  4. Edaravone Enhances Brain-Derived Neurotrophic Factor Production in the Ischemic Mouse Brain

    Directory of Open Access Journals (Sweden)

    Satoshi Okuyama

    2015-04-01

    Full Text Available Edaravone, a clinical drug used to treat strokes, protects against neuronal cell death and memory loss in the ischemic brains of animal models through its antioxidant activity. In the present study, we subcutaneously administrated edaravone to mice (3 mg/kg/day for three days immediately after bilateral common carotid artery occlusion, and revealed through an immunohistochemical analysis that edaravone (1 accelerated increases in the production of brain-derived neurotrophic factor (BDNF in the hippocampus; (2 increased the number of doublecortin-positive neuronal precursor cells in the dentate gyrus subgranular zone; and (3 suppressed the ischemia-induced inactivation of calcium-calmodulin-dependent protein kinase II in the hippocampus. We also revealed through a Western blotting analysis that edaravone (4 induced the phosphorylation of cAMP response element-binding (CREB, a transcription factor that regulates BDNF gene expression; and (5 induced the phosphorylation of extracellular signal-regulated kinases 1/2, an upstream signal factor of CREB. These results suggest that the neuroprotective effects of edaravone following brain ischemia were mediated not only by the elimination of oxidative stress, but also by the induction of BDNF production.

  5. Derivation of Accident-Specific Material-at-Risk Equivalency Factors

    Energy Technology Data Exchange (ETDEWEB)

    Jason P. Andrus; Dr. Chad L. Pope

    2012-05-01

    A novel method for calculating material at risk (MAR) dose equivalency developed at the Idaho National Laboratory (INL) now allows for increased utilization of dose equivalency for facility MAR control. This method involves near-real time accounting for the use of accident and material specific release and transport. It utilizes all information from the committed effective dose equation and the five factor source term equation to derive dose equivalency factors which can be used to establish an overall facility or process MAR limit. The equivalency factors allow different nuclide spectrums to be compared for their respective dose consequences by relating them to a specific quantity of an identified reference nuclide. The ability to compare spectrums to a reference limit ensures that MAR limits are in fact bounding instead of attempting to establish a representative or bounding spectrum which may lead to unintended or unanalyzed configurations. This methodology is then coupled with a near real time material tracking system which allows for accurate and timely material composition information and corresponding MAR equivalency values. The development of this approach was driven by the complex nature of processing operations in some INL facilities. This type of approach is ideally suited for facilities and processes where the composition of the MAR and possible release mechanisms change frequently but in well defined fashions and in a batch-type nature.

  6. Prostate-derived Ets factor, an oncogenic driver in breast cancer.

    Science.gov (United States)

    Sood, Ashwani K; Geradts, Joseph; Young, Jessica

    2017-05-01

    Prostate-derived Ets factor (PDEF), a member of the Ets family of transcription factors, differs from other family members in its restricted expression in normal tissues and its unique DNA-binding motif. These interesting attributes coupled with its aberrant expression in cancer have rendered PDEF a focus of increasing interest by tumor biologists. This review provides a current understanding of the characteristics of PDEF expression and its role in breast cancer. The bulk of the evidence is consistent with PDEF overexpression in most breast tumors and an oncogenic role for this transcription factor in breast cancer. In addition, high PDEF expression in estrogen receptor-positive breast tumors showed significant correlation with poor overall survival in several independent cohorts of breast cancer patients. Together, these findings demonstrate PDEF to be an oncogenic driver of breast cancer and a biomarker of poor prognosis in this cancer. Based on this understanding and the limited expression of PDEF in normal human tissues, the development of PDEF-based therapeutics for prevention and treatment of breast cancer is also discussed.

  7. Effect of glial cell line-derived neurotrophic factor on retinal function after experimental branch retinal vein occlusion

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Dornonville de la Cour, Morten; Kyhn, Maria Voss

    2012-01-01

    The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs.......The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs....

  8. Plasma brain-derived neurotrophic factor and reverse dipping pattern of nocturnal blood pressure in patients with cardiovascular risk factors.

    Directory of Open Access Journals (Sweden)

    Manabu Kadoya

    Full Text Available Basic studies have shown that brain-derived neurotrophic factor (BDNF has critical roles in the survival, growth, maintenance, and death of central and peripheral neurons, while it is also involved in regulation of the autonomic nervous system. Furthermore, recent clinical studies have suggested potential role of plasma BDNF in the circulatory system.We investigated the mutual relationships among plasma BDNF, patterns of nocturnal blood pressure changes (dippers, non-dippers, extra-dippers, and reverse-dippers, and cardiac autonomic function as determined by heart rate variability (HRV.This was a cross-sectional study of patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA Study from October 2010 to November 2012.Two-hundred fifty patients with 1 or more cardiovascular risk factor(s (obesity, smoking, presence of cardiovascular event history, hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease were enrolled.Plasma BDNF levels (natural logarithm transformed were significantly (p = 0.001 lower in reverse-dipper patients (7.18±0.69 pg/ml, mean ± SD, n = 36 as compared to dippers (7.86±0.86 pg/ml, n = 100. Multiple logistic regression analysis showed that BDNF (odds ratios: 0.417, 95% confidence interval: 0.228-0.762, P = 0.004 was the sole factor significantly and independently associated with the reverse-dippers as compared with dippers. Furthermore, plasma BDNF level was significantly and positively correlated with the time-domain (SDNN, SDANN5, CVRR and frequency-domain (LF of HRV parameters. Finally, multiple logistic regression analyses showed that the relationship between plasma BDNF and the reverse-dippers was weakened, yet remained significant or borderline significant even after adjusting for HRV parameters.Low plasma BDNF was independently associated with patients showing a reverse-dipper pattern of nocturnal blood pressure, in which an imbalance of cardiac autonomic function

  9. Safety of recombinant human platelet-derived growth factor-BB in Augment® Bone Graft

    Directory of Open Access Journals (Sweden)

    Luis A Solchaga

    2012-12-01

    Full Text Available This article discusses nonclinical and clinical data regarding the safety of recombinant human platelet-derived growth factor-BB as a component of the Augment® Bone Graft (Augment. Augment is a bone graft substitute intended to be used as an alternative to autologous bone graft in the fusion of hindfoot and ankle joints. Nonclinical studies included assessment of the pharmacokinetic profile of intravenously administered recombinant human platelet-derived growth factor-BB in rat and dog, effects of intravenous administration of recombinant human platelet-derived growth factor-BB in a reproductive and development toxicity study in rats, and chronic toxicity and carcinogenicity of Augment in a 12-month implantation model. These studies showed that systemic exposure was brief and clearance was rapid. No signs of toxicity, carcinogenicity, or tumor promotion were observed even with doses far exceeding the maximum clinical dose. Results of clinical trials (605 participants and commercial use of recombinant human platelet-derived growth factor-BB containing products indicate that these products are not associated with increased incidence of adverse events or cancer. The safety data presented provide evidence that recombinant human platelet-derived growth factor-BB is a safe therapeutic when used in combination products as a single administration during surgical procedures for bone repair and fusion. There is no evidence associating use of recombinant human platelet-derived growth factor-BB in Augment with chronic toxicity, carcinogenicity, or tumor promotion.

  10. Expression of platelet-derived growth factor and its receptors in proliferative disorders of fibroblastic origin.

    Science.gov (United States)

    Smits, A; Funa, K; Vassbotn, F S; Beausang-Linder, M; af Ekenstam, F; Heldin, C H; Westermark, B; Nistér, M

    1992-03-01

    Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of connective tissue-derived cells in vitro. Less is known about its functions in vivo, and the role of PDGF in the development of human tumors has not been clarified. The authors have investigated the occurrence of PDGF and PDGF receptors in a series of proliferative disorders of fibroblastic origin using immunohistochemical and in situ hybridization techniques. High expression of PDGF beta-receptor mRNA and protein was found in the malignant tumors, and also in some benign lesions, such as dermatofibroma. In all these cases, benign as well as malignant, the PDGF B-chain mRNA, and less clearly, the PDGF A-chain mRNA, were coexpressed with the beta-receptor. In contrast, high expression of PDGF alpha-receptor mRNA was only found in fully malignant lesions, i.e., malignant fibrous histiocytoma. These data indicate that an autocrine growth stimulation via the PDGF beta-receptor could occur in an early phase of tumorigenesis, and may be a necessary but insufficient event for the progression into fully malignant human connective tissue lesions.

  11. Suppression of human monocyte tissue factor induction by red wine phenolics and synthetic derivatives of resveratrol.

    Science.gov (United States)

    Kaur, Gurjeet; Roberti, Marinella; Raul, Francis; Pendurthi, Usha R

    2007-01-01

    Prevention of cardiovascular disease through nutritional supplements is growing in popularity throughout the world. Multiple epidemiologic studies found that moderate consumption of alcohol, particularly red wine, lowers mortality rates from coronary heart diseases (CHD). Chronic inflammation and atherosclerosis associated with CHD culminate in aberrant intravascular expression of tissue factor (TF), which triggers blood coagulation leading to thrombosis, a major cause for heart attack. We showed earlier that two red wine phenolics, resveratrol and quercetin, suppressed TF induction in endothelial cells. In the present study, we investigated efficacy of seven resveratrol derivatives, which were shown to be effective in regulating cancer cell growth in vitro at much lower concentrations than the parent compound resveratrol, in inhibiting TF induction in peripheral blood mononuclear cells (PBMCs). We also tested possible synergistic effects of resveratrol and quercetin with the other major red wine phenolics in suppression of lipopolysaccharide-induced TF expression in human PBMCs. We found that several resveratrol derivatives were 2- to 10-fold more efficient than resveratrol in inhibiting TF induction. Our study found no evidence for synergism among red wine polyphenolics. These data suggest that structural alterations of resveratrol can be effective in producing potent antithrombotic agents that will have therapeutic potential in the improvement of cardiovascular health and prevention of CHD. Among major red wine phenolics, quercetin appears to be the predominant suppressor of TF induction.

  12. Suppression of human monocyte tissue factor induction by red wine phenolics and synthetic derivatives of resveratrol

    Science.gov (United States)

    Kaur, Gurjeet; Roberti, Marinella; Raul, Francis; Pendurthi, Usha R.

    2010-01-01

    Prevention of cardiovascular disease through nutritional supplements is growing in popularity throughout the world. Multiple epidemiologic studies found that moderate consumption of alcohol, particularly red wine, lowers mortality rates from coronary heart diseases (CHD). Chronic inflammation and atherosclerosis associated with CHD culminate in aberrant intravascular expression of tissue factor (TF), which triggers blood coagulation leading to thrombosis, a major cause for heart attack. We showed earlier that two red wine phenolics, resveratrol and quercetin, suppressed TF induction in endothelial cells. In the present study, we investigated efficacy of seven resveratrol derivatives, which were shown to be effective in regulating cancer cell growth in vitro at much lower concentrations than the parent compound resveratrol, in inhibiting TF induction in peripheral blood mononuclear cells (PBMCs). We also tested possible synergistic effects of resveratrol and quercetin with the other major red wine phenolics in suppression of lipopolysaccharide-induced TF expression in human PBMCs. We found that several resveratrol derivatives were 2- to 10-fold more efficient than resveratrol in inhibiting TF induction. Our study found no evidence for synergism among red wine polyphenolics. These data suggest that structural alterations of resveratrol can be effective in producing potent antithrombotic agents that will have therapeutic potential in the improvement of cardiovascular health and prevention of CHD. Among major red wine phenolics, quercetin appears to be the predominant suppressor of TF induction. PMID:16507316

  13. Derivation of ingestion dose conversion factors for the U-238 decay series

    International Nuclear Information System (INIS)

    Jenkins, P.H.; Nicoll, R.M.; Doty, R.L.

    1978-01-01

    Dose conversion factors (DCF's) for the U-238 decay series were derived for use in the assessment of potential doses to man, through several ingestion pathways, by radionuclide deposition from radioactive airborne effluents. The methodology used, although similar to that outlined in the U.S. Nuclear Regulatory Commission's Regulatory Guide 1.109, is complicated by consideration of the ingrowth of decay products. Eight ingestion pathways were considered: (1) fresh vegetables, (2) stored vegetables, (3) milk from cows that eat pasture grass, (4) milk from cows that eat stored feed, (5) goat milk - pasture grass, (6) goat milk - stored feed, (7) beef - pasture grass, and (8) beef - stored feed. Radionuclide deposition was assumed to occur for the entire operational lifetime of the facility. Because the expected operational lifetime may vary from facility to facility, DCF's were calculated for six lifetimes: 10, 15, 20, 25, 30, and 35 years. DCF's were calculated for each of 13 'parent' nuclides in the decay series, with each DCF considering the ingrowth of all subsequent nuclides in the series. The methodology used to derive the DCF's is detailed, and DCF's normalized to a deposition rate of the parent nuclide of 1 μCi m -2 s -1 are reported. (author)

  14. The Use of Recombinant Human Platelet-Derived Growth Factor for Maxillary Sinus Augmentation.

    Science.gov (United States)

    Kubota, Atsushi; Sarmiento, Hector; Alqahtani, Mohammed Saad; Llobell, Arturo; Fiorellini, Joseph P

    The maxillary sinus augmentation procedure has become a predictable treatment to regenerate bone for implant placement. The purpose of this study was to evaluate the effect of recombinant human platelet-derived growth factor BB (rhPDGF-BB) combined with a deproteinized cancellous bovine bone graft for sinus augmentation. The lateral window approach was used for maxillary sinuses with minimal residual bone. After a healing period of 4 months, dental implants were placed and then restored following a 2-month osseointegration period. The result demonstrated increased bone height and ISQ values and a 100% survival rate. This study indicates that the addition of rhPDGF-BB to deproteinized cancellous bovine bone accelerated the healing period in maxillary sinuses with minimal native bone.

  15. Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy.

    Science.gov (United States)

    Sugg, Kristoffer B; Korn, Michael A; Sarver, Dylan C; Markworth, James F; Mendias, Christopher L

    2017-03-01

    The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth. © 2017 Federation of European Biochemical Societies.

  16. Insulin-Like Growth Factor Axis Expression in Dental Pulp Cells Derived From Carious Teeth

    Directory of Open Access Journals (Sweden)

    Hanaa Esa Alkharobi

    2018-04-01

    Full Text Available The insulin-like growth factor (IGF axis plays an important role in dental tissue regeneration and most components of this axis are expressed in human dental pulp cells (DPCs. In our previous study, we analyzed IGF axis gene expression in DPCs and demonstrated a novel role of IGF binding protein (IGFBP-2 and -3 in coordinating mineralized matrix formation in differentiating DPCs. A more recent study from our laboratory partially characterized dental pulp stem cells from teeth with superficial caries (cDPCs and showed that their potential to differentiate odontoblasts and/or into osteoblasts is enhanced by exposure to the mild inflammatory conditions characteristic of superficial caries. In the present study, we examine whether changes apparent in IGF axis expression during osteogenic differentiation of healthy DPCs are also apparent in DPCs derived from carious affected teeth.

  17. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Brassard, Patrice; Adser, Helle

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) has an important role in regulating maintenance, growth and survival of neurons. However, the main source of circulating BDNF in response to exercise is unknown. To identify whether the brain is a source of BDNF during exercise, eight volunteers rowed for 4...... h while simultaneous blood samples were obtained from the radial artery and the internal jugular vein. To further identify putative cerebral region(s) responsible for BDNF release, mouse brains were dissected and analysed for BDNF mRNA expression following treadmill exercise. In humans, a BDNF...... release from the brain was observed at rest (P BDNF, while that contribution decreased following 1 h of recovery. In mice, exercise induced a three...

  18. [BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF): NEUROBIOLOGY AND MARKER VALUE IN NEUROPSYCHIATRY].

    Science.gov (United States)

    Levada, O A; Cherednichenko, N V

    2015-01-01

    In this review current publications about neurobiology and marker value of brain derived neurotrophic factor (BDNF) in neuropsychiatry are analyzed. It is shown that BDNF is an important member of the family of neurotrophins which widely represented in various structures of the CNS. In prenatal period BDNF is involved in all stages of neuronal networks formation, and in the postnatal period its main role is maintaining the normal brain architectonics, involvement in the processes of neurogenesis and realization of neuroprotective functions. BDNF plays an important role in learning and memory organization, food and motor behavior. BDNF brain expression decreases with age, as well as in degenerative and vascular dementias, affective, anxiety, and behavioral disorders. The reducing of BDNF serum, level reflects the decreasing of its cerebral expression and could be used as a neurobiological marker of these pathological processes but the rising of its concentration could indicate the therapy effectiveness.

  19. Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity

    Directory of Open Access Journals (Sweden)

    Francesca eCalabrese

    2014-12-01

    Full Text Available Cytokines are key regulatory mediators involved in the host response to immunological challenges, but also play a critical role in the communication between the immune and the central nervous system. For this, their expression in both systems is under a tight regulatory control. However, pathological conditions may lead to an overproduction of pro-inflammatory cytokines that may have a detrimental impact on central nervous system. In particular, they may damage neuronal structure and function leading to deficits of neuroplasticity, the ability of nervous system to perceive, respond and adapt to external or internal stimuli.In search of the mechanisms by which pro-inflammatory cytokines may affect this crucial brain capability, we will discuss one of the most interesting hypotheses: the involvement of the neurotrophin brain-derived neurotrophic factor, which represents one of the major mediators of neuroplasticity.

  20. Possible Role of Brain-Derived Neurotrophic Factor (BDNF) in Autism Spectrum Disorder: Current Status

    International Nuclear Information System (INIS)

    Halepoto, D. M.; Bashir, S.; AL-Ayadhi, L.

    2014-01-01

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays a vital role in the growth, development, maintenance, and function of several neuronal systems. The purpose of this review is to document the support for the involvement of this molecule in the maintenance of normal cognitive, emotional functioning, and to outline recent developments in the content of Autism spectrum disorder (ASD). Current and future treatment development can be guided by developing understanding of this molecules actions in the brain and the ways the expression of BDNF can be planned. Over the years, research findings suggested a critical role played by BDNF in the development of autism including increased serum concentrations of BDNF in children with autism and identification of different forms of BDNF in families of autistic individuals. (author)

  1. Possible Role of Brain-Derived Neurotrophic Factor (BDNF) in Autism Spectrum Disorder: Current Status

    Energy Technology Data Exchange (ETDEWEB)

    Halepoto, D. M.; Bashir, S.; AL-Ayadhi, L. [King Saud Univ., Riyadh (Saudi Arabia). Dept. of Physiology

    2014-04-15

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays a vital role in the growth, development, maintenance, and function of several neuronal systems. The purpose of this review is to document the support for the involvement of this molecule in the maintenance of normal cognitive, emotional functioning, and to outline recent developments in the content of Autism spectrum disorder (ASD). Current and future treatment development can be guided by developing understanding of this molecules actions in the brain and the ways the expression of BDNF can be planned. Over the years, research findings suggested a critical role played by BDNF in the development of autism including increased serum concentrations of BDNF in children with autism and identification of different forms of BDNF in families of autistic individuals. (author)

  2. The systemic exposure to inhaled beclometasone/formoterol pMDI with valved holding chamber is independent of age and body size

    DEFF Research Database (Denmark)

    Govoni, Mirco; Piccinno, Annalisa; Lucci, Germano

    2015-01-01

    BACKGROUND: Asthma guidelines recommend prescription of inhaled corticosteroids at a reduced dosage in children compared to older patients in order to minimize the systemic exposure and risk of unwanted side effects. In children, pressurized metered dose inhalers (pMDI) are recommended in combina......BACKGROUND: Asthma guidelines recommend prescription of inhaled corticosteroids at a reduced dosage in children compared to older patients in order to minimize the systemic exposure and risk of unwanted side effects. In children, pressurized metered dose inhalers (pMDI) are recommended......-dipropionate) was evaluated over 8 h from three studies, each performed in a different age and body size group. Children (7-11 years, n = 20), adolescents (12-17 years, n = 29) and adults (≥18 years, n = 24) received a single dose of beclometasone/formoterol (children: 200 μg/24 μg, adolescents and adults: 400 μg/24 μg) via...

  3. Expression of Hepatoma-derived growth factor family members in the adult central nervous system

    Directory of Open Access Journals (Sweden)

    Abouzied Mekky M

    2006-01-01

    Full Text Available Abstract Background Hepatoma-derived growth factor (HDGF belongs to a polypeptide family containing five additional members called HDGF related proteins 1–4 (HRP-1 to -4 and Lens epithelial derived growth factor. Whereas some family members such as HDGF and HRP-2 are expressed in a wide range of tissues, the expression of others is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3 only in the nervous system. Here we investigated the expression of HDGF, HRP-2 and HRP-3 in the central nervous system of adult mice on the cellular level by immunohistochemistry. In addition we performed Western blot analysis of various brain regions as well as neuronal and glial cell cultures. Results HDGF was rather evenly expressed throughout all brain regions tested with the lowest expression in the substantia nigra. HRP-2 was strongly expressed in the thalamus, prefrontal and parietal cortex, neurohypophysis, and the cerebellum, HRP-3 in the bulbus olfactorius, piriform cortex and amygdala complex. HDGF and HRP-2 were found to be expressed by neurons, astrocytes and oligodendrocytes. In contrast, strong expression of HRP-3 in the adult nervous system is restricted to neurons, except for very weak expression in oligodendrocytes in the brain stem. Although the majority of neurons are HRP-3 positive, some like cerebellar granule cells are negative. Conclusion The coexpression of HDGF and HRP-2 in glia and neurons as well as the coexpression of all three proteins in many neurons suggests different functions of members of the HDGF protein family in cells of the central nervous system that might include proliferation as well as cell survival. In addition the restricted expression of HRP-3 point to a special function of this family member for neuronal cells.

  4. Acceleration of wound healing with stem cell-derived growth factors.

    Science.gov (United States)

    Tamari, Masayuki; Nishino, Yudai; Yamamoto, Noriyuki; Ueda, Minoru

    2013-01-01

    Recently, it has been revealed that bone marrow-derived mesenchymal stem cells (MSCs) accelerate the healing of skin wounds. Although the proliferative capacity of MSCs decreases with age, MSCs secrete many growth factors. The present study examined the effect of mesenchymal stem cell-conditioned medium (MSC-CM) on wound healing. The wound-healing process was observed macroscopically and histologically using an excisional wound-splinting mouse model, and the expression level of hyaluronic acid related to the wound healing process was observed to evaluate the wound-healing effects of MSC, MSC-CM, and control (phosphate-buffered saline). The MSC and MSC-CM treatments accelerated wound healing versus the control group. At 7 days after administration, epithelialization was accelerated, thick connective tissue had formed in the skin defect area, and the wound area was reduced in the MSC and MSC-CM groups versus the control group. At 14 days, infiltration of inflammatory cells was decreased versus 7 days, and the wounds were closed in the MSC and MSC-CM groups, while a portion of epithelium was observed in the control group. At 7 and 14 days, the MSC and MSC-CM groups expressed significantly higher levels of hyaluronic acid versus the control group (P wound healing versus the control group to a similar degree. Accordingly, it is suggested that the MSC-CM contains growth factor derived from stem cells, is able to accelerate wound healing as well as stem cell transplantation, and may become a new therapeutic method for wound healing in the future.

  5. Pharmacodynamics of recombinant activated factor VII and plasma-derived factor VII in a cohort of severe FVII deficient patients.

    Science.gov (United States)

    van Geffen, Mark; Mathijssen, Natascha C J; Holme, Pål A; Laros-van Gorkom, Britta A P; van Kraaij, Marian G J; Masereeuw, Roselinde; Peyvandi, Flora; van Heerde, Waander L

    2013-07-01

    Recombinant activated factor VII (rFVIIa) and plasma-derived factor VII (pdFVII) are used to prevent bleedings in severe FVII deficient patients, despite their short half-lifes. It is suggested that FVII levels of 15-20 IU/dL are sufficient to maintain hemostasis. We analyzed the pharmacodynamic effects of FVII substitution therapy in the Nijmegen Hemostasis Assay (NHA) that simultaneously measures thrombin and plasmin generation. Ten severe FVII deficient patients were treated with 20 μg/kg rFVIIa or 25 IU/kg pdFVII in a cross-over design. Thrombin generation lag-time (TG-LT) was identified as an effect-response parameter. Pharmacodynamic analysis using a maximum effect model showed 50% reduction of the TG-LT effect at ~2 IU/dL FVII activity for both rFVIIa and pdFVII. The FVII activity to obtain TG-LT comparable to the upper limit of normal range in healthy controls (4 min) was given by the effective concentration (ECnormal), showing sufficient hemostasis at 3-4 IU/dL FVII activity. No association was seen between FVII activity and other thrombin or plasmin generation parameters as measured by NHA. In conclusion, 3-4 IU/dL FVII activity seems sufficient to maintain hemostasis in patients with severe FVII deficiency during prophylaxis. These data may suggest a potential value for measurement of TG-LT in the monitoring of FVII(a) therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Statistical Analysis of Instantaneous Frequency Scaling Factor as Derived From Optical Disdrometer Measurements At KQ Bands

    Science.gov (United States)

    Zemba, Michael; Nessel, James; Houts, Jacquelynne; Luini, Lorenzo; Riva, Carlo

    2016-01-01

    The rain rate data and statistics of a location are often used in conjunction with models to predict rain attenuation. However, the true attenuation is a function not only of rain rate, but also of the drop size distribution (DSD). Generally, models utilize an average drop size distribution (Laws and Parsons or Marshall and Palmer. However, individual rain events may deviate from these models significantly if their DSD is not well approximated by the average. Therefore, characterizing the relationship between the DSD and attenuation is valuable in improving modeled predictions of rain attenuation statistics. The DSD may also be used to derive the instantaneous frequency scaling factor and thus validate frequency scaling models. Since June of 2014, NASA Glenn Research Center (GRC) and the Politecnico di Milano (POLIMI) have jointly conducted a propagation study in Milan, Italy utilizing the 20 and 40 GHz beacon signals of the Alphasat TDP#5 Aldo Paraboni payload. The Ka- and Q-band beacon receivers provide a direct measurement of the signal attenuation while concurrent weather instrumentation provides measurements of the atmospheric conditions at the receiver. Among these instruments is a Thies Clima Laser Precipitation Monitor (optical disdrometer) which yields droplet size distributions (DSD); this DSD information can be used to derive a scaling factor that scales the measured 20 GHz data to expected 40 GHz attenuation. Given the capability to both predict and directly observe 40 GHz attenuation, this site is uniquely situated to assess and characterize such predictions. Previous work using this data has examined the relationship between the measured drop-size distribution and the measured attenuation of the link]. The focus of this paper now turns to a deeper analysis of the scaling factor, including the prediction error as a function of attenuation level, correlation between the scaling factor and the rain rate, and the temporal variability of the drop size

  7. Application of Convolution Neural Network to the forecasts of flare classification and occurrence using SOHO MDI data

    Science.gov (United States)

    Park, Eunsu; Moon, Yong-Jae

    2017-08-01

    A Convolutional Neural Network(CNN) is one of the well-known deep-learning methods in image processing and computer vision area. In this study, we apply CNN to two kinds of flare forecasting models: flare classification and occurrence. For this, we consider several pre-trained models (e.g., AlexNet, GoogLeNet, and ResNet) and customize them by changing several options such as the number of layers, activation function, and optimizer. Our inputs are the same number of SOHO)/MDI images for each flare class (None, C, M and X) at 00:00 UT from Jan 1996 to Dec 2010 (total 1600 images). Outputs are the results of daily flare forecasting for flare class and occurrence. We build, train, and test the models on TensorFlow, which is well-known machine learning software library developed by Google. Our major results from this study are as follows. First, most of the models have accuracies more than 0.7. Second, ResNet developed by Microsoft has the best accuracies : 0.86 for flare classification and 0.84 for flare occurrence. Third, the accuracies of these models vary greatly with changing parameters. We discuss several possibilities to improve the models.

  8. Effect of brain-derived neurotrophic factor on the formation of psycho-vegetative syndrome with brain injury

    Directory of Open Access Journals (Sweden)

    Selyanina N.V.

    2016-09-01

    Full Text Available Aim: to determine the role of brain-derived neurotrophic factor in the formation and forecasting of psycho-vegetative syndrome in patients with cerebral mild to moderate injury. Material and Methods. There have been 150 patients with contusion of the brain, examined. Indicators of neurological, psycho-vegetative status, quantitative content of brain-derived neurotrophic factor (BDNF and nerve growth factor (NGF in the serum were studied. Results. At patients with brain contusion neurological, psycho-vegetative disturbances and decrease neurotrophic factors are determined. It was found to depend of the content of BDNF and psycho-vegetative indicators. Conclusion. The level of brain-derived neurotrophic factor serum (less than 300 pg/ml is a predictor of psycho-vegetative syndrome in the long term of the brain injury.

  9. EGR3 Immediate Early Gene and the Brain-Derived Neurotrophic Factor in Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Bianca Pfaffenseller

    2018-02-01

    Full Text Available Bipolar disorder (BD is a severe psychiatric illness with a consistent genetic influence, involving complex interactions between numerous genes and environmental factors. Immediate early genes (IEGs are activated in the brain in response to environmental stimuli, such as stress. The potential to translate environmental stimuli into long-term changes in brain has led to increased interest in a potential role for these genes influencing risk for psychiatric disorders. Our recent finding using network-based approach has shown that the regulatory unit of early growth response gene 3 (EGR3 of IEGs family was robustly repressed in postmortem prefrontal cortex of BD patients. As a central transcription factor, EGR3 regulates an array of target genes that mediate critical neurobiological processes such as synaptic plasticity, memory and cognition. Considering that EGR3 expression is induced by brain-derived neurotrophic factor (BDNF that has been consistently related to BD pathophysiology, we suggest a link between BDNF and EGR3 and their potential role in BD. A growing body of data from our group and others has shown that peripheral BDNF levels are reduced during mood episodes and also with illness progression. In this same vein, BDNF has been proposed as an important growth factor in the impaired cellular resilience related to BD. Taken together with the fact that EGR3 regulates the expression of the neurotrophin receptor p75NTR and may also indirectly induce BDNF expression, here we propose a feed-forward gene regulatory network involving EGR3 and BDNF and its potential role in BD.

  10. Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8

    International Nuclear Information System (INIS)

    Grob, P.M.; David, E.; Warren, T.C.; DeLeon, R.P.; Farina, P.R.; Homon, C.A.

    1990-01-01

    Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL-8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons

  11. Adhesion of nitrile rubber (NBR) to polyethylene terephthalate (PET) fabric. Part 1: PET surface modification by methylenediphenyl di-isocyanate (MDI)

    Science.gov (United States)

    Razavizadeh, Mahmoud; Jamshidi, Masoud

    2016-01-01

    Fiber to rubber adhesion is an important subject in rubber composite industry. It is well known that surface physical, mechanical and chemical treatments are effective methods to improve interfacial bonding. Ultra violet (UV) light irradiation is an efficient method which is used to increase interfacial interactions. In this research UV assisted chemical modification of PET fabric was used to increase its bonding to nitrile rubber (NBR). NBR is perfect selection to produce fuel and oil resistant rubber parts but it has weak bonding to fabrics. For this purpose at first, the PET fabric was carboxylated under UV irradiation and then methylenediphenyl diisocyanate (MDI) was reacted and grafted to carboxylated PET. T-peel test was used to evaluate PET fabric to NBR bonding strength. Attenuated total reflectance-Fourier transform infrared spectroscopy (FTIR-AT) was used to assess surface modifications of the PET fabrics. The chemical composition of the PET surfaces before and after carboxylation and MDI grafting was investigated by X-ray photoelectron spectroscopy (XPS). It was found that at vulcanizing temperature of 150 °C, carboxylation in contrary to MDI grafting, improved considerably PET to NBR adhesion. Finally effect of curing temperature on PET to NBR bonding strength was determined. It was found that increasing vulcanizing temperature to 170 °C caused considerable improvement (about 134%) in bonding strength.

  12. Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7 hypothalamic neurons.

    Science.gov (United States)

    Takahashi, Hiroyuki; Takata, Fuyuko; Matsumoto, Junichi; Machida, Takashi; Yamauchi, Atsushi; Dohgu, Shinya; Kataoka, Yasufumi

    2015-02-20

    Insulin signaling in the hypothalamus plays an important role in food intake and glucose homeostasis. Hypothalamic neuronal functions are modulated by glial cells; these form an extensive network connecting the neurons and cerebral vasculature, known as the neurovascular unit (NVU). Brain pericytes are periendothelial accessory structures of the blood-brain barrier and integral members of the NVU. However, the interaction between pericytes and neurons is largely unexplored. Here, we investigate whether brain pericytes could affect hypothalamic neuronal insulin signaling. Our immunohistochemical observations demonstrated the existence of pericytes in the mouse hypothalamus, exhibiting immunoreactivity of platelet-derived growth factor receptor β (a pericyte marker), and laminin, a basal lamina marker. We then exposed a murine hypothalamic neuronal cell line, GT1-7, to conditioned medium obtained from primary cultures of rat brain pericytes. Pericyte-conditioned medium (PCM), but not astrocyte- or aortic smooth muscle cell-conditioned medium, increased the insulin-stimulated phosphorylation of Akt in GT1-7 cells in a concentration-dependent manner. PCM also enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor β without changing its expression or localization in cytosolic or plasma membrane fractions. These results suggest that pericytes, rather than astrocytes, increase insulin sensitivity in hypothalamic neurons by releasing soluble factors under physiological conditions in the NVU. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Use of a probabilistic PBPK/PD model to calculate Data Derived Extrapolation Factors for chlorpyrifos.

    Science.gov (United States)

    Poet, Torka S; Timchalk, Charles; Bartels, Michael J; Smith, Jordan N; McDougal, Robin; Juberg, Daland R; Price, Paul S

    2017-06-01

    A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model combined with Monte Carlo analysis of inter-individual variation was used to assess the effects of the insecticide, chlorpyrifos and its active metabolite, chlorpyrifos oxon in humans. The PBPK/PD model has previously been validated and used to describe physiological changes in typical individuals as they grow from birth to adulthood. This model was updated to include physiological and metabolic changes that occur with pregnancy. The model was then used to assess the impact of inter-individual variability in physiology and biochemistry on predictions of internal dose metrics and quantitatively assess the impact of major sources of parameter uncertainty and biological diversity on the pharmacodynamics of red blood cell acetylcholinesterase inhibition. These metrics were determined in potentially sensitive populations of infants, adult women, pregnant women, and a combined population of adult men and women. The parameters primarily responsible for inter-individual variation in RBC acetylcholinesterase inhibition were related to metabolic clearance of CPF and CPF-oxon. Data Derived Extrapolation Factors that address intra-species physiology and biochemistry to replace uncertainty factors with quantitative differences in metrics were developed in these same populations. The DDEFs were less than 4 for all populations. These data and modeling approach will be useful in ongoing and future human health risk assessments for CPF and could be used for other chemicals with potential human exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Urinary brain-derived neurotrophic factor as a biomarker of executive functioning.

    Science.gov (United States)

    Koven, Nancy S; Collins, Larisa R

    2014-01-01

    Neurotrophins such as brain-derived neurotrophic factor (BDNF) are vital for neuronal survival and adaptive plasticity. With high BDNF gene expression in the prefrontal cortex, BDNF is a potential regulatory factor for building and maintaining cognitive reserves. Recent studies suggest that individual differences in executive functioning, a broad cognitive domain reliant upon frontal lobe structure and function, are governed in part by variance in BDNF polymorphisms. However, as neurogenetic data are not necessarily indicative of in vivo neurochemistry, this study examines the relationship between executive functioning and the neurotransmitter by measuring peripheral BDNF levels. Fifty-two healthy young adults completed a battery of standardized executive function tests. BDNF levels, adjusted for creatinine, were quantified with enzyme-linked immunosorbent assay of urine samples taken at the time of testing. BDNF concentration was positively associated with cognitive flexibility but had no relationship with working memory, abstract reasoning/planning, self-monitoring/response inhibition, or fluency. These results individuate cognitive flexibility as the specific facet of executive functioning associated with in vivo BDNF levels. This study also validates urinary BDNF as a peripheral biomarker of cognition in healthy adults. © 2014 S. Karger AG, Basel.

  15. Are the changes in the peripheral brain-derived neurotrophic factor levels due to platelet activation?

    Science.gov (United States)

    Serra-Millàs, Montserrat

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in central nervous system development, neurogenesis and neuronal plasticity. BDNF is also expressed in several non-neuronal tissues, and it could play an important role in other processes, such as cancer, angiogenesis, etc. Platelets are the major source of peripheral BDNF. However, platelets also contain high amounts of serotonin; they express specific surface receptors during activation, and a multitude of pro-inflammatory and immunomodulatory bioactive compounds are secreted from the granules. Until recently, there was insufficient knowledge regarding the relationship between BDNF and platelets. Recent studies showed that BDNF is present in two distinct pools in platelets, in α-granules and in the cytoplasm, and only the BDNF in the granules is secreted following stimulation, representing 30% of the total BDNF in platelets. BDNF has an important role in the pathophysiology of depression. Low levels of serum BDNF have been described in patients with major depressive disorder, and BDNF levels increased with chronic antidepressant treatment. Interestingly, there is an association between depression and platelet function. This review analyzed studies that evaluated the relationship between BDNF and platelet activation and the effect of treatments on both parameters. Only a few studies consider this possible confounding factor, and it could be very important in diseases such as depression, which show changes in both parameters. PMID:27014600

  16. Brain-derived Neurotrophic Factor (BDNF) and gray matter volume in bipolar disorder.

    Science.gov (United States)

    Poletti, S; Aggio, V; Hoogenboezem, T A; Ambrée, O; de Wit, H; Wijkhuijs, A J M; Locatelli, C; Colombo, C; Arolt, V; Drexhage, H A; Benedetti, F

    2017-02-01

    Bipolar Disorder (BD) is a severe psychiatric condition characterized by grey matter (GM) volumes reduction. Neurotrophic factors have been suggested to play a role in the neuroprogressive changes during the illness course. In particular peripheral brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in BD. The aim of our study was to investigate if serum levels of BDNF are associated with GM volumes in BD patients and healthy controls (HC). We studied 36 inpatients affected by a major depressive episode in course of BD type I and 17 HC. Analysis of variance was performed to investigate the effect of diagnosis on GM volumes in the whole brain. Threshold for significance was PBDNF levels compared with HC. Reduced GM volumes in BD patients compared to HC were observed in several brain areas, encompassing the caudate head, superior temporal gyrus, insula, fusiform gyrus, parahippocampal gyrus, and anterior cingulate cortex. The interaction analysis between BDNF levels and diagnosis showed a significant effect in the middle frontal gyrus. HC reported higher BDNF levels associated with higher GM volumes, whereas no association between BDNF and GM volumes was observed in BD. Our study seems to suggest that although the production of BDNF is increased in BD possibly to prevent and repair neural damage, its effects could be hampered by underlying neuroinflammatory processes interfering with the neurodevelopmental role of BDNF. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  18. Effect of brain-derived neurotrophic factor (BDNF) on sperm quality of normozoospermic men.

    Science.gov (United States)

    Safari, Hassan; Khanlarkhani, Neda; Sobhani, Aligholi; Najafi, Atefeh; Amidi, Fardin

    2017-07-05

    The neurotrophin family of proteins and their receptors act as important proliferative and pro-survival factors in differentiation of nerve cells and are thought to play key roles in the development of reproductive tissues and normal function of spermatozoa. The objective of the present study was to evaluate the effect of Brain-Derived Neurotrophic Factor (BDNF) on the sperm viability and motility, lipid peroxidation (LPO), mitochondrial activity and concentration of leptin, nitric oxide (NO) and insulin in normozoospermic men. Semen samples from 20 normozoospermic men were divided into three groups: (i) control, (ii) BDNF and (iii) BDNF + K252a. BDNF and K252a were added in the dose of 0.133 and 0.1 nM, respectively. Viability was assessed by eosin-nigrosin staining technique, and motility was observed by microscopy. NO concentration and mitochondrial activity were measured with flow cytometry, and LPO was analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Results showed that exogenous BDNF at 0.133 nM could significantly (p < 0.05) influence viability, motility, NO concentration, mitochondrial activity and LPO content. Secretions of insulin and leptin by human sperm were increased in cells exposed to the exogenous BDNF, whereas viability, mitochondrial activity and insulin and leptin secretions were decreased in cells exposed to the K252.

  19. Inhibition of the mitogenic response to platelet-derived growth factor by terbinafine

    International Nuclear Information System (INIS)

    St Denny, I.H.; Glinka, K.G.; Nemecek, G.M.; Stuetz, A.

    1987-01-01

    Terbinafine (T;(E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic which inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated mitogenesis. The inclusion of 1.5-5μM T in fibroblast incubation media was associated with increased [ 3 H]thymidine incorporation into DNA in the presence and absence of PDGF. However, T at concentrations above 6μM reduced DNA synthesis in control and PDGF-exposed cultures to nearly undetectable levels. Under a phase-contrast microscope, fibroblasts appeared morphologically normal at T concentrations as high as 25 μM. Neither the uptake of [ 3 H]thymidine nor the specific binding of 125 I-PDGF to fibroblast receptors was significantly affected by 10 μM T. Furthermore, concentrations of T which antagonized the mitogenic response to PDGF also interfered with fibroblast growth factor-induced mitogenesis. Together, these data suggest that T has the ability to inhibit the in vitro action of PDGF via a post-receptor mechanism

  20. Inhibition of the mitogenic response to platelet-derived growth factor by terbinafine

    Energy Technology Data Exchange (ETDEWEB)

    St. Denny, I.H.; Glinka, K.G.; Nemecek, G.M. (Sandoz Research Institute, East Hanover, NJ (USA)); Stuetz, A. (Sandoz Forschungsinstitut, Vienna (Austria))

    1987-05-01

    Terbinafine (T;(E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic which inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated mitogenesis. The inclusion of 1.5-5{mu}M T in fibroblast incubation media was associated with increased ({sup 3}H)thymidine incorporation into DNA in the presence and absence of PDGF. However, T at concentrations above 6{mu}M reduced DNA synthesis in control and PDGF-exposed cultures to nearly undetectable levels. Under a phase-contrast microscope, fibroblasts appeared morphologically normal at T concentrations as high as 25 {mu}M. Neither the uptake of ({sup 3}H)thymidine nor the specific binding of {sup 125}I-PDGF to fibroblast receptors was significantly affected by 10 {mu}M T. Furthermore, concentrations of T which antagonized the mitogenic response to PDGF also interfered with fibroblast growth factor-induced mitogenesis. Together, these data suggest that T has the ability to inhibit the in vitro action of PDGF via a post-receptor mechanism.

  1. Treatment with glial derived neurotropic factor (GDNF attenuates oxidative damages of spinal

    Directory of Open Access Journals (Sweden)

    Tao Li

    2016-05-01

    Full Text Available Spinal cord injury (SCI is a serious and debilitating issue being suffered by wide population worldwide. Extensive treatment approaches have been tested and being verified for their efficacy. Owing to the nature of central nervous system (CNS, the resident stem cells would be triggered in response to any sort of trauma with nerve factors as their communication signals. Apart from physical injuries, damages due to oxidative stress also need to be addressed while CNS repair mechanism takes place. This study looks at the potential of glial derived nerve factor (GDNF in addressing the SCI in regard to oxidative damages. A total of 60 Wistar rats were clustered into five groups and GDNF at various concentrations was tested in each group. Assessments in terms of oxidative stress parameters were noted and analyzed accordingly. It was noted that GDNF had reduced oxidative damages and increased the levels of anti-oxidants in dose-dependent manner (p < 0.05. Though treatment with 10 mg/mL and 20 mg/mL showed significant changes as compared to control group, these treatment modalities remained insignificant among each other. In conclusion, we demonstrated that GDNF exerted a neuro-protective effect on CNS by inducing anti-oxidants and reducing the levels of oxidative stress in SCI induced rat models.

  2. [Changes of the Expression of Brain Derived Neurotrophic Factors in Rats Trachea Induced by Acrolein Exposure].

    Science.gov (United States)

    Yuan, Bing; Yang, Rui-an; Zhao, Wei; Xu, Yan-yan; Dan, Qi-qin; Zhang, Yun-hui

    2015-07-01

    To investigate expressional changes of brain derived neurotrophic factor (BDNF) in the trachea of rats with acrolein inhalation. Twenty two SD rats were divided into 2 groups: the rats in experimental group were subjected to acrolein inhalation for the induce of trachea inflammatory injury, while the rats with saline (NS) inhalation were as control. All the rats were sacrificed in 1,3,6 weeks after acrolein (n = 11 at each time point) or saline inhalation (n = 11 at each time point), the samples of trachea epithelium were harvested. The immunohistochemistry and in situ hybridization was performed to detect the location of BDNF protein and mRNA in trachea. The expression of BDNF mRNA in the trachea tissues were determined by RT-PCR. There are positive cells in epithelium of trachea for BDNF protein and mRNA, with cytoplasm staining. The expression of BDNF mRNA in the trachea was increased at 1 week after acrolein inhalation (P 0.05). The inflammatory injury in trachea induced by acrolein exposure could be associated with the increased expression of BDNF. BDNF may be one of the crucial inflammatory factors in the process of inflammatory reaction in trachea with acrolein stimulation.

  3. Brain-derived neurotrophic factor mediates cognitive improvements following acute exercise.

    Science.gov (United States)

    Borror, Andrew

    2017-09-01

    The mechanisms causing improved cognition following acute exercise are poorly understood. This article proposes that brain-derived neurotrophic factor (BDNF) is the main factor contributing to improved cognition following exercise. Additionally, it argues that cerebral blood flow (CBF) and oxidative stress explain the release of BDNF from cerebral endothelial cells. One way to test these hypotheses is to block endothelial function and measure the effect on BDNF levels and cognitive performance. The CBF and oxidative stress can also be examined in relationship to BDNF using a multiple linear regression. If these hypotheses are true, there would be a linear relationship between CBF+oxidative stress and BDNF levels as well as between BDNF levels and cognitive performance. The novelty of these hypotheses comes from the emphasis on the cerebral endothelium and the interplay between BDNF, CBF, and oxidative stress. If found to be valid, these hypotheses would draw attention to the cerebral endothelium and provide direction for future research regarding methods to optimize BDNF release and enhance cognition. Elucidating these mechanisms would provide direction for expediting recovery in clinical populations, such as stroke, and maintaining quality of life in the elderly. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The brain-derived neurotrophic factor pathway, life stress, and chronic multi-site musculoskeletal pain.

    Science.gov (United States)

    Generaal, Ellen; Milaneschi, Yuri; Jansen, Rick; Elzinga, Bernet M; Dekker, Joost; Penninx, Brenda W J H

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) disturbances and life stress, both independently and in interaction, have been hypothesized to induce chronic pain. We examined whether (a) the BDNF pathway (val(66)met genotype, gene expression, and serum levels), (b) early and recent life stress, and (c) their interaction are associated with the presence and severity of chronic multi-site musculoskeletal pain. Cross-sectional data are from 1646 subjects of the Netherlands Study of Depression and Anxiety. The presence and severity of chronic multi-site musculoskeletal pain were determined using the Chronic Pain Grade (CPG) questionnaire. The BDNF val(66)met polymorphism, BDNF gene expression, and BDNF serum levels were measured. Early life stress before the age of 16 was assessed by calculating a childhood trauma index using the Childhood Trauma Interview. Recent life stress was assessed as the number of recent adverse life events using the List of Threatening Events Questionnaire. Compared to val(66)val, BDNF met carriers more often had chronic pain, whereas no differences were found for BDNF gene expression and serum levels. Higher levels of early and recent stress were both associated with the presence and severity of chronic pain (p stress in the associations with chronic pain presence and severity. This study suggests that the BDNF gene marks vulnerability for chronic pain. Although life stress did not alter the impact of BDNF on chronic pain, it seems an independent factor in the onset and persistence of chronic pain. © The Author(s) 2016.

  5. Clinical and biological significance of hepatoma-derived growth factor in Ewing's sarcoma.

    Science.gov (United States)

    Yang, Yang; Li, Hui; Zhang, Fenfen; Shi, Huijuan; Zhen, Tiantian; Dai, Sujuan; Kang, Lili; Liang, Yingjie; Wang, Jin; Han, Anjia

    2013-11-01

    We sought to investigate the clinicopathological significance and biological function of hepatoma-derived growth factor (HDGF) in Ewing's sarcoma. Our results showed that HDGF expression is up-regulated in Ewing's sarcoma. Nuclear HDGF expression is significantly associated with tumour volume (p Ewing's sarcoma cell growth, proliferation and enhances tumourigenesis, both in vitro and in vivo. Meanwhile, HDGF knock-down causes cell cycle arrest and enhanced sensitization to serum starvation-induced apoptosis. Furthermore, recombinant HDGF promotes proliferation and colony formation of Ewing's sarcoma cells. Ninety-eight candidate HDGF downstream genes were identified in Ewing's sarcoma cells using cDNA microarray analysis. In addition, we found that HDGF knock-down inhibited FLI1 expression in Ewing's sarcoma cells at the mRNA and protein levels. Our findings suggest that HDGF exhibits oncogenic properties and may be a novel prognostic factor in Ewing's sarcoma. Targeting HDGF might be a potential therapeutic strategy for Ewing's sarcoma. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. SU-E-T-469: A Practical Approach for the Determination of Small Field Output Factors Using Published Monte Carlo Derived Correction Factors

    International Nuclear Information System (INIS)

    Calderon, E; Siergiej, D

    2014-01-01

    Purpose: Output factor determination for small fields (less than 20 mm) presents significant challenges due to ion chamber volume averaging and diode over-response. Measured output factor values between detectors are known to have large deviations as field sizes are decreased. No set standard to resolve this difference in measurement exists. We observed differences between measured output factors of up to 14% using two different detectors. Published Monte Carlo derived correction factors were used to address this challenge and decrease the output factor deviation between detectors. Methods: Output factors for Elekta's linac-based stereotactic cone system were measured using the EDGE detector (Sun Nuclear) and the A16 ion chamber (Standard Imaging). Measurements conditions were 100 cm SSD (source to surface distance) and 1.5 cm depth. Output factors were first normalized to a 10.4 cm × 10.4 cm field size using a daisy-chaining technique to minimize the dependence of field size on detector response. An equation expressing the relation between published Monte Carlo correction factors as a function of field size for each detector was derived. The measured output factors were then multiplied by the calculated correction factors. EBT3 gafchromic film dosimetry was used to independently validate the corrected output factors. Results: Without correction, the deviation in output factors between the EDGE and A16 detectors ranged from 1.3 to 14.8%, depending on cone size. After applying the calculated correction factors, this deviation fell to 0 to 3.4%. Output factors determined with film agree within 3.5% of the corrected output factors. Conclusion: We present a practical approach to applying published Monte Carlo derived correction factors to measured small field output factors for the EDGE and A16 detectors. Using this method, we were able to decrease the percent deviation between both detectors from 14.8% to 3.4% agreement

  7. Derivation and application of mathematical model for well test analysis with variable skin factor in hydrocarbon reservoirs

    Directory of Open Access Journals (Sweden)

    Pengcheng Liu

    2016-06-01

    Full Text Available Skin factor is often regarded as a constant in most of the mathematical model for well test analysis in oilfields, but this is only a kind of simplified treatment with the actual skin factor changeable. This paper defined the average permeability of a damaged area as a function of time by using the definition of skin factor. Therefore a relationship between a variable skin factor and time was established. The variable skin factor derived was introduced into existing traditional models rather than using a constant skin factor, then, this newly derived mathematical model for well test analysis considering variable skin factor was solved by Laplace transform. The dimensionless wellbore pressure and its derivative changed with dimensionless time were plotted with double logarithm and these plots can be used for type curve fitting. The effects of all the parameters in the expression of variable skin factor were analyzed based on the dimensionless wellbore pressure and its derivative. Finally, actual well testing data were used to fit the type curves developed which validates the applicability of the mathematical model from Sheng-2 Block, Shengli Oilfield, China.

  8. Characterization of buffy coat-derived granulocytes for clinical use: a comparison with granulocyte colony-stimulating factor/dexamethasone-pretreated donor-derived products.

    Science.gov (United States)

    van de Geer, A; Gazendam, R P; Tool, A T J; van Hamme, J L; de Korte, D; van den Berg, T K; Zeerleder, S S; Kuijpers, T W

    2017-02-01

    Buffy coat-derived granulocytes have been described as an alternative to the apheresis product from donors pretreated with dexamethasone and granulocyte colony-stimulating factor (G-CSF). The latter is - dependent on the local and national settings - obtained following a demanding and time-consuming procedure, which is undesirable in critically ill septic patients. In contrast, buffy coat-derived products have a large volume and are often heavily contaminated with red cells and platelets. We developed a new pooled buffy coat-derived product with high purity and small volume, and performed a comprehensive functional characterization of these granulocytes. We pooled ten buffy coats following the production of platelet concentrates. Saline 0·9% was added to decrease the viscosity and the product was split into plasma, red cells and a 'super' buffy coat. Functional data of the granulocytes were compared to those obtained with granulocytes from healthy controls and G-CSF/dexamethasone-pretreated donors. Buffy coat-derived granulocytes showed adhesion, chemotaxis, reactive oxygen species production, degranulation, NETosis and in vitro killing of Staphylococcus aureus, Escherichia coli and Aspergillus species comparable to control and G-CSF/dexamethasone-derived granulocytes. Candida killing was superior compared to G-CSF/dexamethasone-derived granulocytes. Immunophenotyping was normal; especially no signs of activation in the buffy coat-derived granulocytes were seen. Viability was reduced. Buffy coats are readily available in the regular blood production process and would take away the concerns around the apheresis product. The product described appears a promising alternative for transfusion purposes. © 2017 International Society of Blood Transfusion.

  9. Platelet-derived growth factor induces phosphorylation of a 64-kDa nuclear protein

    International Nuclear Information System (INIS)

    Shawver, L.K.; Pierce, G.F.; Kawahara, R.S.; Deuel, T.F.

    1989-01-01

    The platelet-derived growth factor (PDGF) stimulated the phosphorylation of a nuclear protein of 64 kDa (pp64) in nuclei of nontransformed normal rat kidney (NRK) cells. Low levels of phosphorylation of pp64 were observed in nuclei of serum-starved NRK cells. Fetal calf serum (FCS), PDGF, and homodimeric v-sis and PDGF A-chain protein enhanced the incorporation of 32P into pp64 over 4-fold within 30 min and over 8-fold within 2 h of exposure of NRK cells to the growth factors. In contrast, constitutive phosphorylation of 32P-labeled pp64 in nuclei of NRK cells transformed by the simian sarcoma virus (SSV) was high and only minimally stimulated by PDGF and FCS. 32P-Labeled pp64 was isolated from nuclei of PDGF-stimulated nontransformed NRK cells; the 32P of pp64 was labile in 1 M KOH, and pp64 was not significantly recognized by anti-phosphotyrosine antisera, suggesting that the PDGF-induced phosphorylation of pp64 occurred on serine or on threonine residues. However, pp64 from SSV-transformed NRK cell nuclei was significantly stable to base hydrolysis and was immunoprecipitated with anti-phosphotyrosine antisera, suggesting that pp64 from SSV-transformed cell nuclei is phosphorylated also on tyrosine. FCS, PDGF, and PDGF A- and B-chain homodimers thus stimulate the rapid time-dependent phosphorylation of a 64-kDa nuclear protein shortly after stimulation of responsive cells. The growth factor-stimulated phosphorylation of pp64 and the constitutive high levels of pp64 phosphorylation in cells transformed by SSV suggest important roles for pp64 and perhaps regulated nuclear protein kinases and phosphatases in cell division and proliferation

  10. Platelet-Derived Growth Factor BB Influences Muscle Regeneration in Duchenne Muscle Dystrophy.

    Science.gov (United States)

    Piñol-Jurado, Patricia; Gallardo, Eduard; de Luna, Noemi; Suárez-Calvet, Xavier; Sánchez-Riera, Carles; Fernández-Simón, Esther; Gomis, Clara; Illa, Isabel; Díaz-Manera, Jordi

    2017-08-01

    Duchenne muscular dystrophy (DMD) is characterized by a progressive loss of muscle fibers, and their substitution by fibrotic and adipose tissue. Many factors contribute to this process, but the molecular pathways related to regeneration and degeneration of muscle are not completely known. Platelet-derived growth factor (PDGF)-BB belongs to a family of growth factors that regulate proliferation, migration, and differentiation of mesenchymal cells. The role of PDGF-BB in muscle regeneration in humans has not been studied. We analyzed the expression of PDGF-BB in muscle biopsy samples from controls and patients with DMD. We performed in vitro experiments to understand the effects of PDGF-BB on myoblasts involved in the pathophysiology of muscular dystrophies and confirmed our results in vivo by treating the mdx murine model of DMD with repeated i.m. injections of PDGF-BB. We observed that regenerating and necrotic muscle fibers in muscle biopsy samples from DMD patients expressed PDGF-BB. In vitro, PDGF-BB attracted myoblasts and activated their proliferation. Analysis of muscles from the animals treated with PDGF-BB showed an increased population of satellite cells and an increase in the number of regenerative fibers, with a reduction in inflammatory infiltrates, compared with those in vehicle-treated mice. Based on our results, PDGF-BB may play a protective role in muscular dystrophies by enhancing muscle regeneration through activation of satellite cell proliferation and migration. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines

    International Nuclear Information System (INIS)

    Bronzert, D.A.; Pantazis, P.; Antoniades, H.N.; Kasid, A.; Davidson, N.; Dickson, R.B.; Lippman, M.E.

    1987-01-01

    The authors report that human breast cancer cells secrete a growth factor that is biologically and immunologically similar to platelet-derived growth factor (PDGF). Serum-free medium conditioned by estrogen-independent MDA-MB-231 or estrogen-dependent MCF-7 cells contains a mitogenic or competence activity that is capable of inducing incorporation of [ 3 H] thymidine into quiescent Swiss 3T3 cells in the presence of platelet-poor plasma. Like authentic PDGF, the PDGF-like activity produced by breast cancer cells is stable after acid and heat treatment (95 0 C) and inhibited by reducing agents. The mitogenic activity comigrates with a material of ≅30 kDa on NaDodSO 4 /polyacrylamide gels. Immunoprecipitation with PDGF antiserum of proteins from metabolically labeled cell lysates and conditioned medium followed by analysis on nonreducing NaDodSO 4 /polyacrylamide gels identified proteins of 30 and 34 kDa. Upon reduction, the 30- and 34-kDa bands were converted to 15- and 16-kDa bands suggesting that the immunoprecipitated proteins were made up of two disulfide-linked polypeptides similar to PDGF. Hybridization studies with cDNA probes for the A chain PDGF and the B chain of PDGF/SIS identified transcripts for both PDGF chains in the MCF-7 and MDA-MB-231 cells. The data summarized above provide conclusive evidence for the synthesis and hormonally regulated secretion of a PDGF-like mitogen by breast carcinoma cells. Production of a PDGF-like growth factor by breast cancer cell lines may be important in mediating paracrine stimulation of tumor growth

  12. Brain-derived neurotrophic factor reduces inflammation and hippocampal apoptosis in experimental Streptococcus pneumoniae meningitis.

    Science.gov (United States)

    Xu, Danfeng; Lian, Di; Wu, Jing; Liu, Ying; Zhu, Mingjie; Sun, Jiaming; He, Dake; Li, Ling

    2017-08-04

    Streptococcus pneumoniae meningitis is a serious inflammatory disease of the central nervous system (CNS) and is associated with high morbidity and mortality rates. The inflammatory processes initiated by recognition of bacterial components contribute to apoptosis in the hippocampal dentate gyrus. Brain-derived neurotrophic factor (BDNF) has long been recommended for the treatment of CNS diseases due to its powerful neuro-survival properties, as well as its recently reported anti-inflammatory and anti-apoptotic effects in vitro and in vivo. In this study, we investigated the effects of BDNF-related signaling on the inflammatory response and hippocampal apoptosis in experimental models of pneumococcal meningitis. Pretreatment with exogenous BDNF or the tropomyosin-receptor kinase B (TrkB) inhibitor k252a was performed to assess the activation or inhibition of the BDNF/TrkB-signaling axis prior to intracisternal infection with live S. pneumoniae. At 24 h post-infection, rats were assessed for clinical severity and sacrificed to harvest the brains. Paraffin-embedded brain sections underwent hematoxylin and eosin staining to evaluate pathological severity, and cytokine and chemokine levels in the hippocampus and cortex were evaluated by enzyme-linked immunosorbent assay. Additionally, apoptotic neurons were detected in the hippocampal dentate gyrus by terminal deoxynucleotidyl transferase dUTP-nick-end labeling, key molecules associated with the related signaling pathway were analyzed by real-time polymerase chain reaction and western blot, and the DNA-binding activity of nuclear factor kappa B (NF-κB) was measured by electrophoretic mobility shift assay. Rats administered BDNF exhibited reduced clinical impairment, pathological severity, and hippocampal apoptosis. Furthermore, BDNF pretreatment suppressed the expression of inflammatory factors, including tumor necrosis factor α, interleukin (IL)-1β, and IL-6, and increased the expression of the anti

  13. Role of pigment epithelium-derived factor in the involution of hemangioma: Autocrine growth inhibition of hemangioma-derived endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung-Jin [Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Yun, Jang-Hyuk; Heo, Jong-Ik [Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Lee, Eun Hui [Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Min, Hye Sook [Department of Pathology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Choi, Tae Hyun, E-mail: psthchoi@snu.ac.kr [Department of Plastic and Reconstructive Surgery, Seoul National University Children’s Hospital, Seoul 110-744 (Korea, Republic of); Department of Pediatric Plastic and Reconstructive Surgery, Seoul National University Children’s Hospital, Seoul 110-744 (Korea, Republic of); Cho, Chung-Hyun, E-mail: iamhyun@snu.ac.kr [Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Ischemic/Hypoxic Disease Institute, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Cancer Research Institute, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of)

    2014-11-14

    Highlights: • PEDF was expressed and induced during the involuting phase of IH. • PEDF inhibited the cell growth of the involuting HemECs in an autocrine manner. • PEDF suppression restored the impaired cell growth of the involuting HemECs. - Abstract: Hemangioma is a benign tumor derived from abnormal blood vessel growth. Unlike other vascular tumor counterparts, a hemangioma is known to proliferate during its early stage but it is followed by a stage of involution where regression of the tumor occurs. The critical onset leading to the involution of hemangioma is currently not well understood. This study focused on the molecular identities of the involution of hemangioma. We demonstrated that a soluble factor released from the involuting phase of hemangioma-derived endothelial cells (HemECs) and identified pigment epithelium-derived factor (PEDF) as an anti-angiogenic factor that was associated with the growth inhibition of the involuting HemECs. The growth inhibition of the involuting HemECs was reversed by suppression of PEDF in the involuting HemECs. Furthermore, we found that PEDF was more up-regulated in the involuting phase of hemangioma tissues than in the proliferating or the involuted. Taken together, we propose that PEDF accelerates the involution of hemangioma by growth inhibition of HemECs in an autocrine manner. The regulatory mechanism of PEDF expression could be a potential therapeutic target to treat hemangiomas.

  14. The niche-derived glial cell line-derived neurotrophic factor (GDNF induces migration of mouse spermatogonial stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Lisa Dovere

    Full Text Available In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF, a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.

  15. Theobromine up-regulates cerebral brain-derived neurotrophic factor and facilitates motor learning in mice.

    Science.gov (United States)

    Yoneda, Mitsugu; Sugimoto, Naotoshi; Katakura, Masanori; Matsuzaki, Kentaro; Tanigami, Hayate; Yachie, Akihiro; Ohno-Shosaku, Takako; Shido, Osamu

    2017-01-01

    Theobromine, which is a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. Theobromine works as a phosphodiesterase (PDE) inhibitor to increase intracellular cyclic adenosine monophosphate (cAMP). cAMP activates the cAMP-response element-binding protein (CREB), which is involved in a large variety of brain processes, including the induction of the brain-derived neurotrophic factor (BDNF). BDNF supports cell survival and neuronal functions, including learning and memory. Thus, cAMP/CREB/BDNF pathways play an important role in learning and memory. Here, we investigated whether orally administered theobromine could act as a PDE inhibitor centrally and affect cAMP/CREB/BDNF pathways and learning behavior in mice. The mice were divided into two groups. The control group (CN) was fed a normal diet, whereas the theobromine group (TB) was fed a diet supplemented with 0.05% theobromine for 30 days. We measured the levels of theobromine, phosphorylated vasodilator-stimulated phosphoprotein (p-VASP), phosphorylated CREB (p-CREB), and BDNF in the brain. p-VASP was used as an index of cAMP increases. Moreover, we analyzed the performance of the mice on a three-lever motor learning task. Theobromine was detectable in the brains of TB mice. The brain levels of p-VASP, p-CREB, and BDNF were higher in the TB mice compared with those in the CN mice. In addition, the TB mice performed better on the three-lever task than the CN mice did. These results strongly suggested that orally administered theobromine acted as a PDE inhibitor in the brain, and it augmented the cAMP/CREB/BDNF pathways and motor learning in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

    Science.gov (United States)

    Cai, Qian-Ying; Zhang, Heng-Xin; Wang, Chen-Chen; Sun, Hao; Sun, Shu-Qiang; Wang, Yu-Huan; Yan, Hong-Tao; Yang, Xin-Jun

    2017-08-01

    To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P BDNF was positively associated with placental BDNF relative expression (r s  = 0.245, P = 0.02) in the total group. Higher cord blood BDNF levels were independently associated with protection against nondiabetic macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

  17. Cabergoline decreases alcohol drinking and seeking behaviors via glial cell line-derived neurotrophic factor.

    Science.gov (United States)

    Carnicella, Sebastien; Ahmadiantehrani, Somayeh; He, Dao-Yao; Nielsen, Carsten K; Bartlett, Selena E; Janak, Patricia H; Ron, Dorit

    2009-07-15

    Cabergoline is an ergotamine derivative that increases the expression of glial cell line-derived neurotrophic factor (GDNF) in vitro. We recently showed that GDNF in the ventral tegmental area (VTA) reduces the motivation to consume alcohol. We therefore set out to determine whether cabergoline administration decreases alcohol-drinking and -seeking behaviors via GDNF. Reverse transcription polymerase chain reaction (RT-PCR) and Enzyme-Linked ImmunoSorbent Assay (ELISA) were used to measure GDNF levels. Western blot analysis was used for phosphorylation experiments. Operant self-administration in rats and a two-bottle choice procedure in mice were used to assess alcohol-drinking behaviors. Instrumental performance tested during extinction was used to measure alcohol-seeking behavior. The [35S]GTPgammaS binding assay was used to assess the expression and function of the dopamine D2 receptor (D2R). We found that treatment of the dopaminergic-like cell line SH-SY5Y with cabergoline and systemic administration of cabergoline in rats resulted in an increase in GDNF level and in the activation of the GDNF pathway. Cabergoline treatment decreased alcohol-drinking and -seeking behaviors including relapse, and its action to reduce alcohol consumption was localized to the VTA. Finally, the increase in GDNF expression and the decrease in alcohol consumption by cabergoline were abolished in GDNF heterozygous knockout mice. Together, these findings suggest that cabergoline-mediated upregulation of the GDNF pathway attenuates alcohol-drinking behaviors and relapse. Alcohol abuse and addiction are devastating and costly problems worldwide. This study puts forward the possibility that cabergoline might be an effective treatment for these disorders.

  18. Glycan structure of Gc Protein-derived Macrophage Activating Factor as revealed by mass spectrometry.

    Science.gov (United States)

    Borges, Chad R; Rehder, Douglas S

    2016-09-15

    Disagreement exists regarding the O-glycan structure attached to human vitamin D binding protein (DBP). Previously reported evidence indicated that the O-glycan of the Gc1S allele product is the linear core 1 NeuNAc-Gal-GalNAc-Thr trisaccharide. Here, glycan structural evidence is provided from glycan linkage analysis and over 30 serial glycosidase-digestion experiments which were followed by analysis of the intact protein by electrospray ionization mass spectrometry (ESI-MS). Results demonstrate that the O-glycan from the Gc1F protein is the same linear trisaccharide found on the Gc1S protein and that the hexose residue is galactose. In addition, the putative anti-cancer derivative of DBP known as Gc Protein-derived Macrophage Activating Factor (GcMAF, which is formed by the combined action of β-galactosidase and neuraminidase upon DBP) was analyzed intact by ESI-MS, revealing that the activating E. coli β-galactosidase cleaves nothing from the protein-leaving the glycan structure of active GcMAF as a Gal-GalNAc-Thr disaccharide, regardless of the order in which β-galactosidase and neuraminidase are applied. Moreover, glycosidase digestion results show that α-N-Acetylgalactosamindase (nagalase) lacks endoglycosidic function and only cleaves the DBP O-glycan once it has been trimmed down to a GalNAc-Thr monosaccharide-precluding the possibility of this enzyme removing the O-glycan trisaccharide from cancer-patient DBP in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. {sup 14}C-Methylenebisphenylisocyanate ({sup 14}C-MDI). Study of absorption after single dermal and intradermal administration in rats

    Energy Technology Data Exchange (ETDEWEB)

    Leibold, E.; Hoffmann, H.D.; Hildebrand, B

    1999-07-01

    The absorption, distribution and excretion of radioactivity was studied in groups of four male Wistar rats following a single dermal and intradermal administration of {sup 14}C- Methylenebisphenylisocyanate ({sup 14}C-MDI) at nominal dose levels of 4.0 and 0.4 mg/cm{sup 2} for dermal administration and 0.4 mg/animal for intradermal administration. These dose levels nominally corresponded to 40 and 4.0 mg/animal for dermal administration. Considering the animal weights, dose levels corresponded to about 140 and 14 mg/kg body weight (dermal administration) and 1.4 mg/kg body weight (intradermal administration). In the experiments with dermal administration, animals were exposed for 8 hours and sacrificed 8, 24 or 120 h after beginning of exposure. In the experiment with intradermal administration, animals were sacrificed 120 h after treatment. After dermal administration of {sup 14}C-MDI, mean recoveries of radioactivity from all dose groups were in the range from 97.86 to 108.07% of the total radioactivity administered. Generally, the largest proportion of radioactivity was found at the application site and dressing. The total amount of radioactivity absorbed (including excreta, cage wash, tissues/organs and carcass) increased with increasing sacrifice time. Dermal absorption was very low and quantitatively similar at both dose levels; maximally ca. 0.9 % of the applied radioactivity was absorbed. After intradermal administration of {sup 14}C-MDI, the mean recovery of radioactivity was 100.90 % of the radioactivity administered. The largest proportion of radioactivity was found at the application site. The total amount of radioactivity absorbed (including excreta, cage wash, tissues/organs and carcass) amounted to about 26 % of the radioactivity applied. Irrespective of the mode of administration of 1{sup 4C}-MDI, concentrations of radioactivity in tissues and organs generally were below 1 {mu}g Eq/g at 120 h after administration. In summary, the results of this

  20. Leiomyoma-derived transforming growth factor-β impairs bone morphogenetic protein-2-mediated endometrial receptivity.

    Science.gov (United States)

    Doherty, Leo F; Taylor, Hugh S

    2015-03-01

    To determine whether transforming growth factor (TGF)-β3 is a paracrine signal secreted by leiomyoma that inhibits bone morphogenetic protein (BMP)-mediated endometrial receptivity and decidualization. Experimental. Laboratory. Women with symptomatic leiomyomas. Endometrial stromal cells (ESCs) and leiomyoma cells were isolated from surgical specimens. Leiomyoma-conditioned media (LCM) was applied to cultured ESC. The TGF-β was blocked by two approaches: TGF-β pan-specific antibody or transfection with a mutant TGF-β receptor type II. Cells were then treated with recombinant human BMP-2 to assess BMP responsiveness. Expression of BMP receptor types 1A, 1B, 2, as well as endometrial receptivity mediators HOXA10 and leukemia inhibitory factor (LIF). Enzyme-linked immunosorbent assay showed elevated TGF-β levels in LCM. LCM treatment of ESC reduced expression of BMP receptor types 1B and 2 to approximately 60% of pretreatment levels. Preincubation of LCM with TGF-β neutralizing antibody or mutant TGF receptor, but not respective controls, prevented repression of BMP receptors. HOXA10 and LIF expression was repressed in recombinant human BMP-2 treated, LCM exposed ESC. Pretreatment of LCM with TGF-β antibody or transfection with mutant TGF receptor prevented HOXA10 and LIF repression. Leiomyoma-derived TGF-β was necessary and sufficient to alter endometrial BMP-2 responsiveness. Blockade of TGF-β prevents repression of BMP-2 receptors and restores BMP-2-stimulated expression of HOXA10 and LIF. Blockade of TGF signaling is a potential strategy to improve infertility and pregnancy loss associated with uterine leiomyoma. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  1. Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder.

    Science.gov (United States)

    Tripp, Adam; Oh, Hyunjung; Guilloux, Jean-Philippe; Martinowich, Keri; Lewis, David A; Sibille, Etienne

    2012-11-01

    The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known. Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdnf(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results. Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex. These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis

  2. Brain derived neurotrophic factor (BDNF) and autism spectrum disorders (ASD) in childhood.

    Science.gov (United States)

    Bryn, V; Halvorsen, B; Ueland, T; Isaksen, J; Kolkova, K; Ravn, K; Skjeldal, O H

    2015-07-01

    Neurotrophic factors are essential regulators of neuronal maturation including synaptic synthesis. Among those, Brain derived neurotrophic factor (BDNF) has been in particular focus in the understanding of autism spectrum disorders (ASD). The aim of our study was to investigate whether BNDF could be used as diagnostic/biological marker for ASD. For this purpose we examined the plasma levels of BDNF and the precursors pro- BDNF in patients with ASD and compared it with non-autistic controls; determined whether there was a correlation between the BDNF and proBDNF levels and clinical severity. We also investigated the coding region of BDNF identify for well-variations which could be associated to ASD. The 65 ASD patients (51 boys) were enrolled from a recent completed epidemiological survey covering two counties (Oppland and Hedmark) in Norway. The mean age of the total number of children who participated in this study was 11,7 years. 30 non-autistic children were included as controls, 14 boys and 16 girls. The mean age was 11.3 years. Exclusion criteria for control group were individuals suffering from either neurological, endocrine, or immune insuffiency. Patients with ASD were characterized by moderately but significantly elevated plasma levels of BDNF compared to matched controls. No differences were observed in the proBDNF level between patients and controls. Within the ASD group, children with intellectual disability demonstrated increased BDNF, but not proBDNF levels, while the presence of ADHD had no impact on circulating proBDNF or BDNF. No further associations between plasma proBDNF or BDNF and other clinical demographics were observed. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  3. Determinants of Blood Brain-Derived Neurotrophic Factor Blood Levels in Patients with Alcohol Use Disorder.

    Science.gov (United States)

    Nubukpo, Philippe; Ramoz, Nicolas; Girard, Murielle; Malauzat, Dominique; Gorwood, Philip

    2017-07-01

    Blood brain-derived neurotrophic factor (BDNF) levels are influenced by both addiction and mood disorders, as well as somatic conditions, gender, and genetic polymorphisms, leading to widely varying results. Depressive symptoms and episodes are frequently observed in patients with alcohol use disorder, and vary widely over time, making it a challenge to determine which aspects are specifically involved in variations of serum BDNF levels in this population. We assessed 227 patients with alcohol dependence involved in a detoxification program, at baseline and after a follow-up of 6 months, for the Alcohol Use Disorders Identification Test score, the length of alcohol dependence, and the number of past detoxification programs. The Beck Depression Inventory and information on current tobacco and alcohol use, suicidal ideation, body mass index, age, gender, and psychotropic treatments were also collected. Serum BDNF (ELISA) and 2 genetic polymorphisms of the BDNF gene (Val33Met and rs962369) were analyzed. The presence of the Met allele, 2 markers of the history of alcohol dependence (gamma glutamyl transferase and the number of past treatments in detoxification programs), and the presence of a depressive episode (but not depressive score) were significantly associated with the 2 blood levels of BDNF at baseline and after 6 months. After controlling for baseline BDNF levels, the presence of the Met allele and an ongoing depressive episode were the only variables associated with changes in BNDF levels after 6 months. Low serum BDNF levels are associated with characteristics related to alcohol consumption and mood disorders, and variants of the BDNF gene in alcohol use disorder patients. The factors that most strongly influenced changes in serum BDNF levels following treatment in an alcohol detoxification program were variants of the BDNF gene and ongoing depression. Copyright © 2017 by the Research Society on Alcoholism.

  4. Determinants of brain-derived neurotrophic factor (BDNF) in umbilical cord and maternal serum.

    Science.gov (United States)

    Flöck, A; Weber, S K; Ferrari, N; Fietz, C; Graf, C; Fimmers, R; Gembruch, U; Merz, W M

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) plays a fundamental role in brain development; additionally, it is involved in various aspects of cerebral function, including neurodegenerative and psychiatric diseases. Involvement of BDNF in parturition has not been investigated. The aim of our study was to analyze determinants of umbilical cord BDNF (UC-BDNF) concentrations of healthy, term newborns and their respective mothers. This cross-sectional prospective study was performed at a tertiary referral center. Maternal venous blood samples were taken on admission to labor ward; newborn venous blood samples were drawn from the umbilical cord (UC), before delivery of the placenta. Analysis was performed with a commercially available immunoassay. Univariate analyses and stepwise multivariate regression models were applied. 120 patients were recruited. UC-BDNF levels were lower than maternal serum concentrations (median 641 ng/mL, IQR 506 vs. median 780 ng/mL, IQR 602). Correlation between UC- and maternal BDNF was low (R=0.251, p=0.01). In univariate analysis, mode of delivery (MoD), gestational age (GA), body mass index at delivery, and gestational diabetes were determinants of UC-BDNF (MoD and smoking for maternal BDNF, respectively). Stepwise multivariate regression analysis revealed a model with MoD and GA as determinants for UC-BDNF (MoD for maternal BDNF). MoD and GA at delivery are determinants of circulating BDNF in the mother and newborn. We hypothesize that BDNF, like other neuroendocrine factors, is involved in the neuroendocrine cascade of delivery. Timing and mode of delivery may exert BDNF-induced effects on the cerebral function of newborns and their mothers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Enriched environment influences hormonal status and hippocampal brain derived neurotrophic factor in a sex dependent manner.

    Science.gov (United States)

    Bakos, J; Hlavacova, N; Rajman, M; Ondicova, K; Koros, C; Kitraki, E; Steinbusch, H W M; Jezova, D

    2009-12-01

    The present study is aimed at testing the hypothesis that an enriched environment (EE) induces sex-dependent changes in stress hormone release and in markers of increased brain plasticity. The focus was on hypothalamic-pituitary-adrenocortical (HPA) axis activity, plasma levels of stress hormones, gene expression of glutamate receptor subunits and concentrations of brain-derived neurotrophic factor (BDNF) in selected brain regions. Rats exposed to EE were housed in groups of 12 in large cages with various objects, which were frequently changed, for 6 weeks. Control animals were housed four per cage under standard conditions. In females the EE-induced rise in hippocampal BDNF, a neurotrophic factor associated with increased neural plasticity, was more pronounced than in males. Similar sex-specific changes were observed in BDNF concentrations in the hypothalamus. EE also significantly attenuated oxytocin and aldosterone levels only in female but not male rats. Plasma testosterone positively correlated with hippocampal BDNF in female but not male rats housed in EE. In male rats housing in EE led to enhanced levels of testosterone and adrenocorticotropic hormone (ACTH), this was not seen in females. Hippocampal glucocorticoid but not mineralocorticoid receptor levels decreased in rats housed in EE irrespective of sex. Housing conditions failed to modify mRNA levels of glutamate receptor type 1 (Glur1) and metabotropic glutamate receptor subtype 5 (mGlur5) subunits of glutamate receptors in the forebrain. Moreover, a negative association between corticosterone and BDNF was observed in both sexes. The results demonstrate that the association between hormones and changes in brain plasticity is sex related. In particular, testosterone seems to be involved in the regulatory processes related to neuroplasticity in females.

  6. Profiling ethanol-targeted transcription factors in human carcinoma cell-derived embryoid bodies.

    Science.gov (United States)

    Mandal, Chanchal; Halder, Debasish; Chai, Jin Choul; Lee, Young Seek; Jung, Kyoung Hwa; Chai, Young Gyu

    2016-01-15

    Fetal alcohol spectrum disorder is a collective term that represents fetal abnormalities associated with maternal alcohol consumption. Prenatal alcohol exposure and related anomalies are well characterized, but the molecular mechanism behind this phenomenon is not yet understood. Few insights have been gained from genetic and epigenetic studies of fetal alcohol spectrum disorder. Our aim was to profile the important molecular regulators of ethanol-related alterations of the genome. For this purpose, we have analyzed the gene expression pattern of human carcinoma cell-derived embryoid bodies in the absence or presence of ethanol. A cDNA microarray analysis was used to profile mRNA expression in embryoid bodies at day 7 with or without ethanol treatment. A total of 493 differentially expressed genes were identified in response to 50 mM ethanol exposure. Of these, 111 genes were up-regulated, and 382 were down-regulated. Gene ontology term enrichment analysis revealed that these genes are involved in important biological processes: neurological system processes, cognition, behavior, sensory perception of smell, taste and chemical stimuli and synaptic transmission. Similarly, the enrichment of disease-related genes included relevant categories such as neurological diseases, developmental disorders, skeletal and muscular disorders, and connective tissue disorders. Furthermore, we have identified a group of 26 genes that encode transcription factors. We validated the relative gene expression of several transcription factors using quantitative real time PCR. We hope that our study substantially contributes to the understanding of the molecular mechanisms underlying the pathology of alcohol-mediated anomalies and facilitates further research. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Expression of platelet-derived growth factor B is upregulated in patients with thoracic aortic dissection.

    Science.gov (United States)

    Meng, Weixin; Liu, Shangdian; Li, Dandan; Liu, Zonghong; Yang, Hui; Sun, Bo; Liu, Hongyu

    2018-04-20

    Thoracic aortic dissection (TAD) is a serious condition requiring urgent treatment to avoid catastrophic consequences. The inflammatory response is involved in the occurrence and development of TAD, possibly potentiated by platelet-derived growth factors (PDGFs). This study aimed to determine whether expression of PDGF-B (a subunit of PDGF-BB) was increased in TAD patients and to explore the factors responsible for its upregulation and subsequent effects on TAD. Full-thickness ascending aorta wall specimens from TAD patients (n = 15) and control patients (n = 10) were examined for expression of PDGF-B and its receptor (PDGFRB) and in terms of morphology, inflammation, and fibrosis. Blood samples from TAD and control patients were collected to detect plasma levels of PDGF-BB and soluble elastins. Expression levels of PDGF-B, PDGFRB, and collagen I were significantly enhanced in ascending aorta wall specimens from TAD patients compared with controls. Furthermore, soluble elastic fragments and PDGF-BB were significantly increased in plasma from TAD patients compared with controls, and numerous irregular elastic fibers and macrophages were seen in the ascending aorta wall in TAD patients. An increase in elastic fragments in the aorta wall might be responsible for inducing the activation and migration of macrophages to injured sites, leading to elevated expression of PDGF-B, which in turn induces deposition of collagen, disrupts extracellular matrix homeostasis, and increases the stiffness of the aorta wall, resulting in compromised aorta compliance. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  8. Effects of heat-treatment on plasma rich in growth factors-derived autologous eye drop.

    Science.gov (United States)

    Anitua, E; Muruzabal, F; De la Fuente, M; Merayo-Lloves, J; Orive, G

    2014-02-01

    We have developed and characterized a new type of plasma rich in growth factors (PRGF) derived eye-drop therapy for patients suffering from autoimmune diseases. To determine the concentration of several growth factors, proteins, immunoglobulins and complement activity of the heat-inactivated eye-drop and to study its biological effects on cell proliferation and migration of different ocular surface cells, blood from healthy donors was collected, centrifuged and PRGF was prepared avoiding the buffy coat. The half volume of the obtained plasma supernatant from each donor was heat-inactivated at 56 °C for 1 h (heat-inactivated PRGF). The concentration of several proteins involved on corneal wound healing, immunoglubolins G, M and E and functional integrity of the complement system assayed by CH50 test were determined. The proliferative and migratory potential of inactivated and non-inactivated PRGF eye drops were assayed on corneal epithelial cells (HCE), keratocytes (HK) and conjunctival fibroblasts (HConF). Heat-inactivated PRGF preserves the content of most of the proteins and morphogens involved in its wound healing effects while reduces drastically the content of IgE and complement activity. Heat-inactivated PRGF eye drops increased proliferation and migration potential of ocular surface cells with regard to PRGF showing significant differences on proliferation and migration rate of HCE and HConF respectively. In summary, heat-inactivation of PRGF eye drops completely reduced complement activity and deceased significantly the presence of IgE, maintaining the biological activity of PRGF on ocular surface cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. A discrete-time two-factor model for pricing bonds and interest rate derivatives under random volatility

    OpenAIRE

    Heston, Steven L.; Nandi, Saikat

    1999-01-01

    This paper develops a discrete-time two-factor model of interest rates with analytical solutions for bonds and many interest rate derivatives when the volatility of the short rate follows a GARCH process that can be correlated with the level of the short rate itself. Besides bond and bond futures, the model yields analytical solutions for prices of European options on discount bonds (and futures) as well as other interest rate derivatives such as caps, floors, average rate options, yield curv...

  10. A Bilayer Construct Controls Adipose-Derived Stem Cell Differentiation into Endothelial Cells and Pericytes without Growth Factor Stimulation

    Science.gov (United States)

    2011-01-01

    A Bilayer Construct Controls Adipose-Derived Stem Cell Differentiation into Endothelial Cells and Pericytes Without Growth Factor Stimulation...Ph.D.3 This work describes the differentiation of adipose-derived mesenchymal stem cells (ASC) in a composite hy- drogel for use as a vascularized...tissue from a single population of ASC. This work underscores the importance of the extracellular matrix in controlling stem cell phenotype. It is our

  11. The effect of choosing three different C factor formulae derived from NDVI on a fully raster-based erosion modelling

    Science.gov (United States)

    Sulistyo, Bambang

    2016-11-01

    The research was aimed at studying the efect of choosing three different C factor formulae derived from NDVI on a fully raster-based erosion modelling of The USLE using remote sensing data and GIS technique. Methods applied was by analysing all factors affecting erosion such that all data were in the form of raster. Those data were R, K, LS, C and P factors. Monthly R factor was evaluated based on formula developed by Abdurachman. K factor was determined using modified formula used by Ministry of Forestry based on soil samples taken in the field. LS factor was derived from Digital Elevation Model. Three C factors used were all derived from NDVI and developed by Suriyaprasit (non-linear) and by Sulistyo (linear and non-linear). P factor was derived from the combination between slope data and landcover classification interpreted from Landsat 7 ETM+. Another analysis was the creation of map of Bulk Density used to convert erosion unit. To know the model accuracy, model validation was done by applying statistical analysis and by comparing Emodel with Eactual. A threshold value of ≥ 0.80 or ≥ 80% was chosen to justify. The research result showed that all Emodel using three formulae of C factors have coeeficient of correlation value of > 0.8. The results of analysis of variance showed that there was significantly difference between Emodel and Eactual when using C factor formula developed by Suriyaprasit and Sulistyo (non-linear). Among the three formulae, only Emodel using C factor formula developed by Sulistyo (linear) reached the accuracy of 81.13% while the other only 56.02% as developed by Sulistyo (nonlinear) and 4.70% as developed by Suriyaprasit, respectively.

  12. Ketamine induces brain-derived neurotrophic factor expression via phosphorylation of histone deacetylase 5 in rats.

    Science.gov (United States)

    Choi, Miyeon; Lee, Seung Hoon; Park, Min Hyeop; Kim, Yong-Seok; Son, Hyeon

    2017-08-05

    Ketamine shows promise as a therapeutic agent for the treatment of depression. The increased expression of brain-derived neurotrophic factor (BDNF) has been associated with the antidepressant-like effects of ketamine, but the mechanism of BDNF induction is not well understood. In the current study, we demonstrate that the treatment of rats with ketamine results in the dose-dependent rapid upregulation of Bdnf promoter IV activity and expression of Bdnf exon IV mRNAs in rat hippocampal neurons. Transfection of histone deacetylase 5 (HDAC5) into rat hippocampal neurons similarly induces Bdnf mRNA expression in response to ketamine, whereas transfection of a HDAC5 phosphorylation-defective mutant (Ser259 and Ser498 replaced by Ala259 and Ala498), results in the suppression of ketamine-mediated BDNF promoter IV transcriptional activity. Viral-mediated hippocampal knockdown of HDAC5 induces Bdnf mRNA and protein expression, and blocks the enhancing effects of ketamine on BDNF expression in both unstressed and stressed rats, and thereby providing evidence for the role of HDAC5 in the regulation of Bdnf expression. Taken together, our findings implicate HDAC5 in the ketamine-induced transcriptional regulation of Bdnf, and suggest that the phosphorylation of HDAC5 regulates the therapeutic actions of ketamine. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Elevated expression of brain-derived neurotrophic factor facilitates visual imprinting in chicks.

    Science.gov (United States)

    Suzuki, Keiko; Maekawa, Fumihiko; Suzuki, Shingo; Nakamori, Tomoharu; Sugiyama, Hayato; Kanamatsu, Tomoyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

    2012-12-01

    With the aim of elucidating the neural mechanisms of early learning, we studied the role of brain-derived neurotrophic factor (BDNF) in visual imprinting in birds. The telencephalic neural circuit connecting the visual Wulst and intermediate medial mesopallium is critical for imprinting, and the core region of the hyperpallium densocellulare (HDCo), situated at the center of this circuit, has a key role in regulating the activity of the circuit. We found that the number of BDNF mRNA-positive cells in the HDCo was elevated during the critical period, particularly at its onset, on the day of hatching (P0). After imprinting training on P1, BDNF mRNA-positive cells in the HDCo increased in number, and tyrosine phosphorylation of TrkB was observed. BDNF infusion into the HDCo at P1 induced imprinting, even with a weak training protocol that does not normally induce imprinting. In contrast, K252a, an antagonist of Trk, inhibited imprinting. Injection of BDNF at P7, after the critical period, did not elicit imprinting. These results suggest that BDNF promotes the induction of imprinting through TrkB exclusively during the critical period. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  14. Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory.

    Science.gov (United States)

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L

    2016-01-15

    Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Influence of obstetric factors on osteogenic potential of umbilical cord-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Canella Alessandro

    2009-10-01

    Full Text Available Abstract Wharton's jelly from the umbilical cord is a noncontroversial source of mesenchymal stem cells (WJMSCs with high plasticity, proliferation rate and ability to differentiate towards multiple lineages. WJMSCs from different donors have been characterized for their osteogenic potential. Although there is large evidence of WJMSCs plasticity, recently scientific debate has focused on MSCs selection, establishing predictable elements to discriminate the cells with most promising osteoprogenitor cell potential. In the present study a comparative study between the presence of osteoblastic markers and different parameters that pertain to both the newborn and the mother was performed. Umbilical cords were collected after all patients signed the informed consent and local ethical commettee approved the study. Obstetric parameters, including baby's gender and birth weight, mother's age at delivery, gestational stage at parturition and mode of delivery were examined. After characterization and expansion, WJMSCs were analyzed for two osteoblastic markers, alkaline phosphatase (ALP activity, and the expression level of RUNX-2 transcription factor, and for their ability to deposit mineralized matrix after osteogenic induction. We found that osteoblastic potential was not influenced by baby's gender and mode of delivery. On the contrary, the highest degree of osteoblastic potential has been shown by WJMSCs with RUNX-2 high basal levels, selected from umbilical cords of the heaviest term babies. Even if further evaluation is required, our hypothesis is that our findings may help in selecting the optimal umbilical cord donors and in collecting high potential Wharton's jelly-derived osteoprogenitors efficiently.

  16. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons

    Science.gov (United States)

    Murphy, Diane D.; Cole, Nelson B.; Segal, Menahem

    1998-01-01

    Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons. PMID:9736750

  17. Effect of brain-derived neurotrophic factor (BDNF) on hepatocyte metabolism.

    Science.gov (United States)

    Genzer, Yoni; Chapnik, Nava; Froy, Oren

    2017-07-01

    Brain-derived neurotrophic factor (BDNF) plays crucial roles in the development, maintenance, plasticity and homeostasis of the central and peripheral nervous systems. Perturbing BDNF signaling in mouse brain results in hyperphagia, obesity, hyperinsulinemia and hyperglycemia. Currently, little is known whether BDNF affects liver tissue directly. Our aim was to determine the metabolic signaling pathways activated after BDNF treatment in hepatocytes. Unlike its effect in the brain, BDNF did not lead to activation of the liver AKT pathway. However, AMP protein activated kinase (AMPK) was ∼3 times more active and fatty acid synthase (FAS) ∼2-fold less active, suggesting increased fatty acid oxidation and reduced fatty acid synthesis. In addition, cAMP response element binding protein (CREB) was ∼3.5-fold less active together with its output the gluconeogenic transcript phosphoenolpyruvate carboxykinase (Pepck), suggesting reduced gluconeogenesis. The levels of glycogen synthase kinase 3b (GSK3b) was ∼3-fold higher suggesting increased glycogen synthesis. In parallel, the expression levels of the clock genes Bmal1 and Cry1, whose protein products play also a metabolic role, were ∼2-fold increased and decreased, respectively. In conclusion, BDNF binding to hepatocytes leads to activation of catabolic pathways, such as fatty acid oxidation. In parallel gluconeogenesis is inhibited, while glycogen storage is triggered. This metabolic state mimics that of after breakfast, in which the liver continues to oxidize fat, stops gluconeogenesis and replenishes glycogen stores. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The Effects of Acute Exercise on Memory and Brain-Derived Neurotrophic Factor (BDNF).

    Science.gov (United States)

    Etnier, Jennifer L; Wideman, Laurie; Labban, Jeffrey D; Piepmeier, Aaron T; Pendleton, Daniel M; Dvorak, Kelly K; Becofsky, Katie

    2016-08-01

    Acute exercise benefits cognition, and some evidence suggests that brain-derived neurotrophic factor (BDNF) plays a role in this effect. The purpose of this study was to explore the dose-response relationship between exercise intensity, memory, and BDNF. Young adults completed 3 exercise sessions at different intensities relative to ventilator threshold (Vt) (VO 2max , Vt - 20%, Vt + 20%). For each session, participants exercised for approximately 30 min. Following exercise, they performed the Rey Auditory Verbal Learning Test (RAVLT) to assess short-term memory, learning, and long-term memory recall. Twenty-four hours later, they completed the RAVLT recognition trial, which provided another measure of long-term memory. Blood was drawn before exercise, immediately postexercise, and after the 30-min recall test. Results indicated that long-term memory as assessed after the 24-hr delay differed as a function of exercise intensity with the largest benefits observed following maximal intensity exercise. BDNF data showed a significant increase in response to exercise; however, there were no differences relative to exercise intensity and there were no significant associations between BDNF and memory. Future research is warranted so that we can better understand how to use exercise to benefit cognitive performance.

  19. Gene Transfer of Brain-derived Neurotrophic Factor (BDNF) Prevents Neurodegeneration Triggered by FXN Deficiency.

    Science.gov (United States)

    Katsu-Jiménez, Yurika; Loría, Frida; Corona, Juan Carlos; Díaz-Nido, Javier

    2016-05-01

    Friedreich's ataxia is a predominantly neurodegenerative disease caused by recessive mutations that produce a deficiency of frataxin (FXN). Here, we have used a herpesviral amplicon vector carrying a gene encoding for brain-derived neurotrophic factor (BDNF) to drive its overexpression in neuronal cells and test for its effect on FXN-deficient neurons both in culture and in the mouse cerebellum in vivo. Gene transfer of BDNF to primary cultures of mouse neurons prevents the apoptosis which is triggered by the knockdown of FXN gene expression. This neuroprotective effect of BDNF is also observed in vivo in a viral vector-based knockdown mouse cerebellar model. The injection of a lentiviral vector carrying a minigene encoding for a FXN-specific short hairpin ribonucleic acid (shRNA) into the mouse cerebellar cortex triggers a FXN deficit which is accompanied by significant apoptosis of granule neurons as well as loss of calbindin in Purkinje cells. These pathological changes are accompanied by a loss of motor coordination of mice as assayed by the rota-rod test. Coinjection of a herpesviral vector encoding for BDNF efficiently prevents both the development of cerebellar neuropathology and the ataxic phenotype. These data demonstrate the potential therapeutic usefulness of neurotrophins like BDNF to protect FXN-deficient neurons from degeneration.

  20. Effect of different anesthesia techniques on the serum brain-derived neurotrophic factor (BDNF) levels.

    Science.gov (United States)

    Ozer, A B; Demirel, I; Erhan, O L; Firdolas, F; Ustundag, B

    2015-10-01

    Serum Brain-Derived Neurotrophic Factor (BDNF) levels are associated with neurotransmission and cognitive functions. The goal of this study was to examine the effect of general anesthesia on BDNF levels. It was also to reveal whether this effect had a relationship with the surgical stress response or not. The study included 50 male patients, age 20-40, who were scheduled to have inguinoscrotal surgery, and who were in the ASA I-II risk group. The patients were divided into two groups according to the anesthesia techniques used: general (GA) and spinal (SA). In order to measure serum BDNF, cortisol, insulin and glucose levels, blood samples were taken at four different times: before and after anesthesia, end of the surgery, and before transferal from the recovery room. Serum BDNF levels were significantly low (p BDNF and the stress hormones. Our findings suggested that general anesthetics had an effect on serum BDNF levels independent of the stress response. In future, BDNF could be used as biochemical parameters of anesthesia levels, but studies with a greater scope should be carried out to present the relationship between anesthesia and neurotrophins.

  1. Pro-region engineering for improved yeast display and secretion of brain derived neurotrophic factor.

    Science.gov (United States)

    Burns, Michael L; Malott, Thomas M; Metcalf, Kevin J; Puguh, Arthya; Chan, Jonah R; Shusta, Eric V

    2016-03-01

    Brain derived neurotrophic factor (BDNF) is a promising therapeutic candidate for a variety of neurological diseases. However, it is difficult to produce as a recombinant protein. In its native mammalian context, BDNF is first produced as a pro-protein with subsequent proteolytic removal of the pro-region to yield mature BDNF protein. Therefore, in an attempt to improve yeast as a host for heterologous BDNF production, the BDNF pro-region was first evaluated for its effects on BDNF surface display and secretion. Addition of the wild-type pro-region to yeast BDNF production constructs improved BDNF folding both as a surface-displayed and secreted protein in terms of binding its natural receptors TrkB and p75, but titers remained low. Looking to further enhance the chaperone-like functions provided by the pro-region, two rounds of directed evolution were performed, yielding mutated pro-regions that further improved the display and secretion properties of BDNF. Subsequent optimization of the protease recognition site was used to control whether the produced protein was in pro- or mature BDNF forms. Taken together, we have demonstrated an effective strategy for improving BDNF compatibility with yeast protein engineering and secretion platforms. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Brain-derived neurotrophic factor (BDNF) plasma concentration in patients diagnosed with premature ovarian insufficiency (POI).

    Science.gov (United States)

    Czyzyk, Adam; Filipowicz, Dorota; Podfigurna, Agnieszka; Ptas, Paula; Piestrzynska, Malgorzata; Smolarczyk, Roman; Genazzani, Andrea R; Meczekalski, Blazej

    2017-05-01

    Premature ovarian insufficiency (POI) is defined as a cessation of function of ovaries in women younger than 40 years old. Brain-derived neurotrophic factor (BDNF) is a protein critically involved in neuronal growth and metabolism. BDNF also has been shown to be important regulator of oocyte maturation. Recent data show that BDNF can be potentially involved in POI pathology. The aim of the study was to assess the BDNF plasma concentrations in patients diagnosed with idiopathic POI. 23 women diagnosed with POI (age 31 ± 7 years) and 18 (age 31 ± 3) controls were included to the study, matched according to age and body mass index. The BDNF concentrations were measured using competitive enzyme-linked immunosorbent assay (ELISA). Hormonal and metabolic parameters were measured in all individuals, in controls in late follicular phase. The POI group demonstrated lower mean plasma concentrations of BDNF (429.25 ± 65.52 pg/ml) in comparison to healthy controls (479.75 ± 34.75 pg/ml, p = 0.0345). The BDNF plasma concentration correlated negatively (R = -0.79, p BDNF and progesterone in controls. In conclusion, POI patients show significantly lower BDNF plasma concentration and it correlates with the duration of amenorrhea. This observation brings important potential insights to the pathology of POI.

  3. Post-traumatic stress disorder risk and brain-derived neurotrophic factor Val66Met

    Science.gov (United States)

    Zhang, Lei; Li, Xiao-Xia; Hu, Xian-Zhang

    2016-01-01

    Brain-derived neurotrophic factor (BDNF), which regulates neuronal survival, growth differentiation, and synapse formation, is known to be associated with depression and post-traumatic stress disorder (PTSD). However, the molecular mechanism for those mental disorders remains unknown. Studies have shown that BDNF is associated with PTSD risk and exaggerated startle reaction (a major arousal manifestation of PTSD) in United States military service members who were deployed during the wars in Iraq and Afghanistan. The frequency of the Met/Met in BDNF gene was greater among those with PTSD than those without PTSD. Among individuals who experienced fewer lifetime stressful events, the Met carriers have significantly higher total and startle scores on the PTSD Checklist than the Val/Val carriers. In addition, subjects with PTSD showed higher levels of BDNF in their peripheral blood plasma than the non-probable-PTSD controls. Increased BDNF levels and startle response were observed in both blood plasma and brain hippocampus by inescapable tail shock in rats. In this paper, we reviewed these data to discuss BDNF as a potential biomarker for PTSD risk and its possible roles in the onset of PTSD. PMID:27014593

  4. Cs-137 soil to plant transfer factors derived from pot experiments and field studies

    International Nuclear Information System (INIS)

    Horak, O.; Gerzabek, M.H.; Mueck, K.

    1989-11-01

    Soil to plant transfer factors (TF) of 137 Cs for different crop plants were determined in pot experiments, in outdoor experiments with plastic containers of 50 l volume, and in field studies. In all cases the soil contamination with 137 Cs resulted from fallout after the Chernobyl reactor accident. Mean TF derived for outdoor plants on a fresh weight basis, ranged from 0,0017 (leaf vegetables) to 0,059 (rye straw) and showed characteristic differences depending on plant part and species. Generally, for fruits and potato tubers a lower TF was found than for vegetative plant parts. Moreover, the data were compared with those from former experiments, carried out before the Chernobyl accident. There is a good agreement for cereals (with exception of rye) fruit vegetables and fodder crops, while actual TF are substantially lower for potatoes, leaf and root vegetables, but higher for rye. A significant negative correlation was observed between the TF and the soil activity concentrations for 137 Cs. In container experiments the TF were found to be influenced mainly by the clay content of the soil. 11 refs., 2 figs., 2 tabs. (Authors)

  5. Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression.

    Science.gov (United States)

    Kunugi, Hiroshi; Hori, Hiroaki; Adachi, Naoki; Numakawa, Tadahiro

    2010-10-01

    Although the pathophysiology of depressive disorder remains elusive, two hypothetical frameworks seem to be promising: the involvement of hypothalamic pituitary-adrenal (HPA) axis abnormalities and brain-derived neurotrophic factor (BDNF) in the pathogenesis and in the mechanism of action of antidepressant treatments. In this review, we focused on research based on these two frameworks in relation to depression and related conditions and tried to formulate an integrated theory of the disorder. Hormonal challenge tests, such as the dexamethasone/corticotropin-releasing hormone test, have revealed elevated HPA activity (hypercortisolism) in at least a portion of patients with depression, although growing evidence has suggested that abnormally low HPA axis (hypocortisolism) has also been implicated in a variety of stress-related conditions. Several lines of evidence from postmortem studies, animal studies, blood levels, and genetic studies have suggested that BDNF is involved in the pathogenesis of depression and in the mechanism of action of biological treatments for depression. Considerable evidence has suggested that stress reduces the expression of BDNF and that antidepressant treatments increase it. Moreover, the glucocorticoid receptor interacts with the specific receptor of BDNF, TrkB, and excessive glucocorticoid interferes with BDNF signaling. Altered BDNF function is involved in the structural changes and possibly impaired neurogenesis in the brain of depressed patients. Based on these findings, an integrated schema of the pathological and recovery processes of depression is illustrated. © 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.

  6. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor.

    Science.gov (United States)

    Taliaz, Dekel; Loya, Assaf; Gersner, Roman; Haramati, Sharon; Chen, Alon; Zangen, Abraham

    2011-03-23

    Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.

  7. Different levels of brain-derived neurotrophic factor and cortisol in healthy heavy smokers

    Directory of Open Access Journals (Sweden)

    C.D.C. Neves

    2017-10-01

    Full Text Available Studies suggest that brain-derived neurotrophic factor (BDNF and the hypothalamic-pituitary-adrenal (HPA axis modulate dopaminergic activity in response to nicotine and that the concentrations of BDNF and cortisol seem to be dependent on the amount and duration of smoking. Therefore, we investigated BDNF and cortisol levels in smokers ranked by daily cigarette consumption. Twenty-seven adult males (13 non-smokers and 14 smokers participated in the study. The smokers were divided in two groups: light (n=7 and heavy smokers (n=7. Anthropometric parameters and age were paired between the groups, and plasma BDNF and salivary cortisol levels were measured. Saliva samples were collected on awakening, 30 min after awakening, at 10:00 and 12:00 am, 5:00 and 10:00 pm. Additionally, cotinine serum levels were measured in smokers. Heavy smokers had higher mean values of BDNF compared to the control group (P=0.01, whereas no difference was observed in light smokers. Moreover, heavy smokers presented lower cortisol levels in the last collection (10:00 pm than the control group (P=0.02 and presented statically higher values of cotinine than the light smokers (P=0.002. In conclusion, changes in BDNF and cortisol levels (10:00 pm appear to be dependent on heavy cigarette smoking and can be involved in activation and in the relationship between the mesolimbic system and the HPA axis.

  8. Different levels of brain-derived neurotrophic factor and cortisol in healthy heavy smokers.

    Science.gov (United States)

    Neves, C D C; Lacerda, A C R; Lima, L P; Lage, V K S; Balthazar, C H; Leite, H R; Mendonça, V A

    2017-10-19

    Studies suggest that brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis modulate dopaminergic activity in response to nicotine and that the concentrations of BDNF and cortisol seem to be dependent on the amount and duration of smoking. Therefore, we investigated BDNF and cortisol levels in smokers ranked by daily cigarette consumption. Twenty-seven adult males (13 non-smokers and 14 smokers) participated in the study. The smokers were divided in two groups: light (n=7) and heavy smokers (n=7). Anthropometric parameters and age were paired between the groups, and plasma BDNF and salivary cortisol levels were measured. Saliva samples were collected on awakening, 30 min after awakening, at 10:00 and 12:00 am, 5:00 and 10:00 pm. Additionally, cotinine serum levels were measured in smokers. Heavy smokers had higher mean values of BDNF compared to the control group (P=0.01), whereas no difference was observed in light smokers. Moreover, heavy smokers presented lower cortisol levels in the last collection (10:00 pm) than the control group (P=0.02) and presented statically higher values of cotinine than the light smokers (P=0.002). In conclusion, changes in BDNF and cortisol levels (10:00 pm) appear to be dependent on heavy cigarette smoking and can be involved in activation and in the relationship between the mesolimbic system and the HPA axis.

  9. Serum Brain-Derived Neurotrophic Factor Levels in Different Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Mariacarla Ventriglia

    2013-01-01

    Full Text Available Consistent evidence indicates the involvement of the brain-derived neurotrophic factor (BDNF in neurodegenerative disorders such as Alzheimer's disease (AD and Parkinson’s disease (PD. In the present study, we compared serum BDNF in 624 subjects: 266 patients affected by AD, 28 by frontotemporal dementia (FTD, 40 by Lewy body dementia (LBD, 91 by vascular dementia (VAD, 30 by PD, and 169 controls. Our results evidenced lower BDNF serum levels in AD, FTD, LBD, and VAD patients (P<0.001 and a higher BDNF concentration in patients affected by PD (P=0.045. Analyses of effects of pharmacological treatments suggested significantly higher BDNF serum levels in patients taking mood stabilizers/antiepileptics (P=0.009 and L-DOPA (P<0.001 and significant reductions in patients taking benzodiazepines (P=0.020. In conclusion, our results support the role of BDNF alterations in neurodegenerative mechanisms common to different forms of neurological disorders and underline the importance of including drug treatment in the analyses to avoid confounding effects.

  10. Brain-derived neurotrophic factor promoter methylation and cortical thickness in recurrent major depressive disorder.

    Science.gov (United States)

    Na, Kyoung-Sae; Won, Eunsoo; Kang, June; Chang, Hun Soo; Yoon, Ho-Kyoung; Tae, Woo Suk; Kim, Yong-Ku; Lee, Min-Soo; Joe, Sook-Haeng; Kim, Hyun; Ham, Byung-Joo

    2016-02-15

    Recent studies have reported that methylation of the brain-derived neurotrophic factor (BDNF) gene promoter is associated with major depressive disorder (MDD). This study aimed to investigate the association between cortical thickness and methylation of BDNF promoters as well as serum BDNF levels in MDD. The participants consisted of 65 patients with recurrent MDD and 65 age- and gender-matched healthy controls. Methylation of BDNF promoters and cortical thickness were compared between the groups. The right medial orbitofrontal, right lingual, right lateral occipital, left lateral orbitofrontal, left pars triangularis, and left lingual cortices were thinner in patients with MDD than in healthy controls. Among the MDD group, right pericalcarine, right medical orbitofrontal, right rostral middle frontal, right postcentral, right inferior temporal, right cuneus, right precuneus, left frontal pole, left superior frontal, left superior temporal, left rostral middle frontal and left lingual cortices had inverse correlations with methylation of BDNF promoters. Higher levels of BDNF promoter methylation may be closely associated with the reduced cortical thickness among patients with MDD. Serum BDNF levels were significantly lower in MDD, and showed an inverse relationship with BDNF methylation only in healthy controls. Particularly the prefrontal and occipital cortices seem to indicate key regions in which BDNF methylation has a significant effect on structure.

  11. The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies.

    Science.gov (United States)

    Zoladz, J A; Pilc, A

    2010-10-01

    It is well documented that physical activity can induce a number of various stimuli which are able to enhance the strength and endurance performance of muscles. Moreover, regular physical activity can preserve or delay the appearance of several metabolic disorders in the human body. Physical exercise is also known to enhance the mood and cognitive functions of active people, although the physiological backgrounds of these effects remain unclear. In recent years, since the pioneering study in the past showed that physical activity increases the expression of the brain derived neurothophic factor (BDNF) in the rat brain, a number of studies were undertaken in order to establish the link between that neurothrophin and post-exercise enhancement of mood and cognitive functions in humans. It was recently demonstrated that physical exercise can increase plasma and/or serum BDNF concentration in humans. It was also reported that physical exercise or electrical stimulation can increase the BDNF expression in the skeletal muscles. In the present review, we report the current state of research concerning the effect of a single bout of exercise and training on the BDNF expression in the brain, in both the working muscles as well as on its concentrations in the blood. We have concluded that there may be potential benefits of the exercise-induced enhancement of the BDNF expression and release in the brain as well as in the peripheral tissues, resulting in the improvement of the functioning of the body, although this effect, especially in humans, requires more research.

  12. Hemodialysis decreases serum brain-derived neurotrophic factor concentration in humans.

    Science.gov (United States)

    Zoladz, Jerzy A; Śmigielski, Michał; Majerczak, Joanna; Nowak, Łukasz R; Zapart-Bukowska, Justyna; Smoleński, Olgierd; Kulpa, Jan; Duda, Krzysztof; Drzewińska, Joanna; Bartosz, Grzegorz

    2012-12-01

    In the present study we have evaluated the effect of a single hemodialysis session on the brain-derived neurotrophic factor levels in plasma [BDNF](pl) and in serum [BDNF](s) as well as on the plasma isoprostanes concentration [F(2) isoprostanes](pl), plasma total antioxidant capacity (TAC) and plasma cortisol levels in chronic kidney disease patients. Twenty male patients (age 69.8 ± 2.9 years (mean ± SE)) with end-stage renal disease undergoing maintenance hemodialysis on regular dialysis treatment for 15-71 months participated in this study. A single hemodialysis session, lasting 4.2 ± 0.1 h, resulted in a decrease (P = 0.014) in [BDNF](s) by ~42 % (2,574 ± 322 vs. 1,492 ± 327 pg ml(-1)). This was accompanied by an increase (P 0.05) in [BDNF](pl) and the platelets count were observed after a single dialysis session. Furthermore, basal [BDNF](s) in the chronic kidney disease patients was significantly lower (P = 0.03) when compared to the age-matched control group (n = 23). We have concluded that the observed decrease in serum BDNF level after hemodialysis accompanied by elevated [F(2)-Isoprostanes](pl) and decreased plasma TAC might be caused by enhanced oxidative stress induced by hemodialysis.

  13. The Impact of the Brain-Derived Neurotrophic Factor Gene on Trauma and Spatial Processing

    Directory of Open Access Journals (Sweden)

    Jessica K. Miller

    2017-11-01

    Full Text Available The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF gene, given its impact on the integrity of the hippocampal memory system. Research into human navigation also considers the BDNF gene in relation to hippocampal dependent spatial processing. This speculative paper brings together trauma and spatial processing for the first time and presents exploratory research into their interactions with BDNF. We propose that quantifying the impact of BDNF on trauma and spatial processing is critical and may well explain individual differences in clinical trauma treatment outcomes and in navigation performance. Research has already shown that the BDNF gene influences PTSD severity and prevalence as well as navigation behaviour. However, more data are required to demonstrate the precise hippocampal dependent processing mechanisms behind these influences in different populations and environmental conditions. This paper provides insight from recent studies and calls for further research into the relationship between allocentric processing, trauma processing and BDNF. We argue that research into these neural mechanisms could transform PTSD clinical practice and professional support for individuals in trauma-exposing occupations such as emergency response, law enforcement and the military.

  14. The Impact of the Brain-Derived Neurotrophic Factor Gene on Trauma and Spatial Processing.

    Science.gov (United States)

    Miller, Jessica K; McDougall, Siné; Thomas, Sarah; Wiener, Jan

    2017-11-27

    The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD) continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF) gene, given its impact on the integrity of the hippocampal memory system. Research into human navigation also considers the BDNF gene in relation to hippocampal dependent spatial processing. This speculative paper brings together trauma and spatial processing for the first time and presents exploratory research into their interactions with BDNF. We propose that quantifying the impact of BDNF on trauma and spatial processing is critical and may well explain individual differences in clinical trauma treatment outcomes and in navigation performance. Research has already shown that the BDNF gene influences PTSD severity and prevalence as well as navigation behaviour. However, more data are required to demonstrate the precise hippocampal dependent processing mechanisms behind these influences in different populations and environmental conditions. This paper provides insight from recent studies and calls for further research into the relationship between allocentric processing, trauma processing and BDNF. We argue that research into these neural mechanisms could transform PTSD clinical practice and professional support for individuals in trauma-exposing occupations such as emergency response, law enforcement and the military.

  15. Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

    Science.gov (United States)

    Perez-Rodriguez, M Mercedes; New, Antonia S; Goldstein, Kim E; Rosell, Daniel; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David; Siever, Larry J; Hazlett, Erin A

    2017-05-30

    A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype. Copyright © 2017. Published by Elsevier B.V.

  16. Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal brain-derived neurotrophic factor system.

    Science.gov (United States)

    Ni, Yu-Fei; Wang, Hao; Gu, Qiu-Yan; Wang, Fei-Ying; Wang, Ying-Jie; Wang, Jin-Liang; Jiang, Bo

    2018-04-01

    Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression. The changes in brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant antidepressant actions in the FST and TST without affecting the locomotor activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced depressive-like behaviors in the FST, TST and sucrose preference test. Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal BDNF signaling pathway. Blocking PPAR-α and BDNF but not the serotonergic system abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced antidepressant effects in mice by promoting the hippocampal BDNF system.

  17. Diurnal Variation of Plasma Brain-Derived Neurotrophic Factor Levels in Women with Functional Hypothalamic Amenorrhea.

    Science.gov (United States)

    Drakopoulos, Panagiotis; Casarosa, Elena; Bucci, Fiorella; Piccinino, Manuela; Wenger, Jean-Marie; Nappi, Rossella Elena; Polyzos, Nicholas; Genazzani, Andrea Riccardo; Pluchino, Nicola

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) is strongly related to hormonal networks and is modulated by hypothalamic activity. To evaluate plasma BDNF concentration in patients with functional hypothalamic amenorrhea (FHA), with reference to the BDNF circadian rhythm and its relation with the cortisol (F) rhythm, and to assess whether the duration of amenorrhea might influence the BDNF:F ratio in FHA. This was an observational study evaluating 36 amenorrheic and 30 eumenorrheic women. Basal values of BDNF and hormones were examined in blood samples collected from 7:00 to 9:00 h in all the women. Basal BDNF and F levels were determined in blood samples collected in 12 subjects from each group at 8:00, 12:00, 16:00, 20:00, and 24:00 h. BDNF plasma levels are significantly lower in amenorrheic women (p 0.05), sex steroids, and F in FHA. Low plasma BDNF levels in FHA are not significantly correlated with duration of amenorrhea. The 24-hour variation of BDNF in amenorrheic women is significantly lower when compared to the control group, and normal daily variations of BDNF disappeared in FHA patients. F preserved its circadian rhythm in both groups. Interactions between BDNF, the hypothalamus-pituitary-adrenal axis, and sex steroids might be critical in clinical conditions of modified homeostasis/adaptation, such as FHA. © 2015 S. Karger AG, Basel.

  18. Gc protein-derived macrophage activating factor (GcMAF): isoelectric focusing pattern and tumoricidal activity.

    Science.gov (United States)

    Mohamad, Saharuddin Bin; Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Nakagawa, Yoshinori; Kawashima, Ken; Hori, Hitoshi

    2003-01-01

    Gc protein is the precursor for Gc protein-derived macrophage activating factor (GcMAF), with three phenotypes: Gc1f, Gc1s and Gc2, based on its electrophoretic mobility. The difference in electrophoretic mobility is because of the difference in its posttranslational sugar moiety composition. We compared the difference between Gc protein and GcMAF electrophoretic mobility using the isoelectric focusing (IEF) method. The tumoricidal activity of GcMAF-treated macrophage was evaluated after coculture with L-929 cell. The tumoricidal mechanism was investigated using TNF bioassay and nitric oxide (NO) release. The difference in Gc protein and GcMAF electrophoretic mobility was detected. The tumoricidal activity of GcMAF-treated macrophage was detected, but no release of TNF and NO was detected. The difference of isoelectric focusing mobility in Gc protein and GcMAF would be useful to develop a GcMAF detection method. GcMAF increased macrophage tumoricidal activity but TNF and NO release were not involved in the mechanism.

  19. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor.

    Science.gov (United States)

    Szuhany, Kristin L; Bugatti, Matteo; Otto, Michael W

    2015-01-01

    Consistent evidence indicates that exercise improves cognition and mood, with preliminary evidence suggesting that brain-derived neurotrophic factor (BDNF) may mediate these effects. The aim of the current meta-analysis was to provide an estimate of the strength of the association between exercise and increased BDNF levels in humans across multiple exercise paradigms. We conducted a meta-analysis of 29 studies (N = 1111 participants) examining the effect of exercise on BDNF levels in three exercise paradigms: (1) a single session of exercise, (2) a session of exercise following a program of regular exercise, and (3) resting BDNF levels following a program of regular exercise. Moderators of this effect were also examined. Results demonstrated a moderate effect size for increases in BDNF following a single session of exercise (Hedges' g = 0.46, p exercise intensified the effect of a session of exercise on BDNF levels (Hedges' g = 0.59, p = 0.02). Finally, results indicated a small effect of regular exercise on resting BDNF levels (Hedges' g = 0.27, p = 0.005). When analyzing results across paradigms, sex significantly moderated the effect of exercise on BDNF levels, such that studies with more women showed less BDNF change resulting from exercise. Effect size analysis supports the role of exercise as a strategy for enhancing BDNF activity in humans, but indicates that the magnitude of these effects may be lower in females relative to males. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Chemotaxis of primitive hematopoietic cells in response to stromal cell–derived factor-1

    Science.gov (United States)

    Jo, Deog-Yeon; Rafii, Shahin; Hamada, Tsuneyoshi; Moore, Malcolm A.S.

    2000-01-01

    Stromal cell–derived factor-1 (SDF-1) provides a potent chemotactic stimulus for CD34+ hematopoietic cells. We cultured mobilized peripheral blood (PB) and umbilical cord blood (CB) for up to 5 weeks and examined the migratory activity of cobblestone area–forming cells (CAFCs) and long-term culture–initiating cells (LTC-ICs) in a transwell assay. In this system, SDF-1 or MS-5 marrow stromal cells placed in the lower chamber induced transmembrane and transendothelial migration by 2- and 5-week-old CAFCs and LTC-ICs in 3 hours. Transmigration was blocked by preincubation of input CD34+ cells with antibody to CXCR4. Transendothelial migration of CB CAFCs and LTC-ICs was higher than that of PB. We expanded CD34+ cells from CB in serum-free medium with thrombopoietin, flk-2 ligand, and c-kit ligand, with or without IL-3 and found that CAFCs cultured in the absence of IL-3 had a chemotactic response equivalent to noncultured cells, even after 5 weeks. However, addition of IL-3 to the culture reduced this response by 20–50%. These data indicate that SDF-1 induces chemotaxis of primitive hematopoietic cells signaling through CXCR4 and that the chemoattraction could be downmodulated by culture ex vivo. PMID:10619866

  1. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

    Institute of Scientific and Technical Information of China (English)

    De-guo Jiang; Shi-li Jin; Gong-ying Li; Qing-qing Li; Zhi-ruo Li; Hong-xia Ma; Chuan-jun Zhuo; Rong-huan Jiang; Min-jie Ye

    2016-01-01

    Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry andin situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no signiifcant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our ifndings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

  2. Human Obesity Associated with an Intronic SNP in the Brain-Derived Neurotrophic Factor Locus

    Directory of Open Access Journals (Sweden)

    Zongyang Mou

    2015-11-01

    Full Text Available Brain-derived neurotrophic factor (BDNF plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 BDNF SNPs. We observed that the minor C allele of rs12291063 is associated with lower human ventromedial hypothalamic BDNF expression (p < 0.001 and greater adiposity in both adult and pediatric cohorts (p values < 0.05. We further demonstrated that the major T allele for rs12291063 possesses a binding capacity for the transcriptional regulator, heterogeneous nuclear ribonucleoprotein D0B, knockdown of which disrupts transactivation by the T allele. Binding and transactivation functions are both disrupted by substituting C for T. These findings provide a rationale for BDNF augmentation as a targeted treatment for obesity in individuals who have the rs12291063 CC genotype.

  3. Biologic effects of platelet-derived growth factor receptor α blockade in uterine cancer.

    Science.gov (United States)

    Roh, Ju-Won; Huang, Jie; Hu, Wei; Yang, XiaoYun; Jennings, Nicholas B; Sehgal, Vasudha; Sohn, Bo Hwa; Han, Hee Dong; Lee, Sun Joo; Thanapprapasr, Duangmani; Bottsford-Miller, Justin; Zand, Behrouz; Dalton, Heather J; Previs, Rebecca A; Davis, Ashley N; Matsuo, Koji; Lee, Ju-Seog; Ram, Prahlad; Coleman, Robert L; Sood, Anil K

    2014-05-15

    Platelet-derived growth factor receptor α (PDGFRα) expression is frequently observed in many kinds of cancer and is a candidate for therapeutic targeting. This preclinical study evaluated the biologic significance of PDGFRα and PDGFRα blockade (using a fully humanized monoclonal antibody, 3G3) in uterine cancer. Expression of PDGFRα was examined in uterine cancer clinical samples and cell lines, and biologic effects of PDGFRα inhibition were evaluated using in vitro (cell viability, apoptosis, and invasion) and in vivo (orthotopic) models of uterine cancer. PDGFRα was highly expressed and activated in uterine cancer samples and cell lines. Treatment with 3G3 resulted in substantial inhibition of PDGFRα phosphorylation and of downstream signaling molecules AKT and mitogen-activated protein kinase (MAPK). Cell viability and invasive potential of uterine cancer cells were also inhibited by 3G3 treatment. In orthotopic mouse models of uterine cancer, 3G3 monotherapy had significant antitumor effects in the PDGFRα-positive models (Hec-1A, Ishikawa, Spec-2) but not in the PDGFRα-negative model (OVCA432). Greater therapeutic effects were observed for 3G3 in combination with chemotherapy than for either drug alone in the PDGFRα-positive models. The antitumor effects of therapy were related to increased apoptosis and decreased proliferation and angiogenesis. These findings identify PDGFRα as an attractive target for therapeutic development in uterine cancer. ©2014 American Association for Cancer Research.

  4. Role of exercise-induced brain-derived neurotrophic factor production in the regulation of energy homeostasis in mammals

    DEFF Research Database (Denmark)

    Pedersen, Bente K; Pedersen, Maria; Krabbe, Karen S

    2009-01-01

    identifies BDNF as a player not only in central metabolism, but also in regulating energy metabolism in peripheral organs. Low levels of BDNF are found in patients with neurodegenerative diseases, including Alzheimer's disease and major depression. In addition, BDNF levels are low in obesity...... and independently so in patients with type 2 diabetes. Brain-derived neurotrophic factor is expressed in non-neurogenic tissues, including skeletal muscle, and exercise increases BDNF levels not only in the brain and in plasma, but in skeletal muscle as well. Brain-derived neurotrophic factor mRNA and protein...... diabetes may explain the clustering of these diseases. Brain-derived neurotrophic factor is likely to mediate some of the beneficial effects of exercise with regard to protection against dementia and type 2 diabetes....

  5. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor restores erectile function after cavernous nerve injury.

    Science.gov (United States)

    May, Florian; Buchner, Alexander; Schlenker, Boris; Gratzke, Christian; Arndt, Christian; Stief, Christian; Weidner, Norbert; Matiasek, Kaspar

    2013-03-01

    To evaluate the time-course of functional recovery after cavernous nerve injury using glial cell line-derived neurotrophic factor-transduced Schwann cell-seeded silicon tubes. Sections of the cavernous nerves were excised bilaterally (5 mm), followed by immediate bilateral surgical repair. A total of 20 study nerves per group were reconstructed by interposition of empty silicon tubes and silicon tubes seeded with either glial cell line-derived neurotrophic factor-overexpressing or green fluorescent protein-expressing Schwann cells. Control groups were either sham-operated or received bilateral nerve transection without nerve reconstruction. Erectile function was evaluated by relaparotomy, electrical nerve stimulation and intracavernous pressure recording after 2, 4, 6, 8 and 10 weeks. The animals underwent re-exploration only once, and were killed afterwards. The nerve grafts were investigated for the maturation state of regenerating nerve fibers and the fascular composition. Recovery of erectile function took at least 4 weeks in the current model. Glial cell line-derived neurotrophic factor-transduced Schwann cell grafts restored erectile function better than green fluorescent protein-transduced controls and unseeded conduits. Glial cell line-derived neurotrophic factor-transduced grafts promoted an intact erectile response (4/4) at 4, 6, 8 and 10 weeks that was overall significantly superior to negative controls (P cell line-derived neurotrophic factor-transduced grafts compared with negative controls (P = 0.018) and unseeded tubes (P = 0.034). Return of function was associated with the electron microscopic evidence of preganglionic myelinated nerve fibers and postganglionic unmyelinated axons. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor presents a viable approach for the treatment of erectile dysfunction after cavernous nerve injury. © 2013 The Japanese Urological Association.

  6. Large-scale production and properties of human plasma-derived activated Factor VII concentrate.

    Science.gov (United States)

    Tomokiyo, K; Yano, H; Imamura, M; Nakano, Y; Nakagaki, T; Ogata, Y; Terano, T; Miyamoto, S; Funatsu, A

    2003-01-01

    An activated Factor VII (FVIIa) concentrate, prepared from human plasma on a large scale, has to date not been available for clinical use for haemophiliacs with antibodies against FVIII and FIX. In the present study, we attempted to establish a large-scale manufacturing process to obtain plasma-derived FVIIa concentrate with high recovery and safety, and to characterize its biochemical and biological properties. FVII was purified from human cryoprecipitate-poor plasma, by a combination of anion exchange and immunoaffinity chromatography, using Ca2+-dependent anti-FVII monoclonal antibody. To activate FVII, a FVII preparation that was nanofiltered using a Bemberg Microporous Membrane-15 nm was partially converted to FVIIa by autoactivation on an anion-exchange resin. The residual FVII in the FVII and FVIIa mixture was completely activated by further incubating the mixture in the presence of Ca2+ for 18 h at 10 degrees C, without any additional activators. For preparation of the FVIIa concentrate, after dialysis of FVIIa against 20 mm citrate, pH 6.9, containing 13 mm glycine and 240 mm NaCl, the FVIIa preparation was supplemented with 2.5% human albumin (which was first pasteurized at 60 degrees C for 10 h) and lyophilized in vials. To inactivate viruses contaminating the FVIIa concentrate, the lyophilized product was further heated at 65 degrees C for 96 h in a water bath. Total recovery of FVII from 15 000 l of plasma was approximately 40%, and the FVII preparation was fully converted to FVIIa with trace amounts of degraded products (FVIIabeta and FVIIagamma). The specific activity of the FVIIa was approximately 40 U/ micro g. Furthermore, virus-spiking tests demonstrated that immunoaffinity chromatography, nanofiltration and dry-heating effectively removed and inactivated the spiked viruses in the FVIIa. These results indicated that the FVIIa concentrate had both high specific activity and safety. We established a large-scale manufacturing process of human plasma-derived

  7. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II-derived

  8. Hypoxic stress simultaneously stimulates vascular endothelial growth factor via hypoxia-inducible factor-1α and inhibits stromal cell-derived factor-1 in human endometrial stromal cells.

    Science.gov (United States)

    Tsuzuki, Tomoko; Okada, Hidetaka; Cho, Hisayuu; Tsuji, Shoko; Nishigaki, Akemi; Yasuda, Katsuhiko; Kanzaki, Hideharu

    2012-02-01

    Hypoxia of the human endometrium is a physiologic event occurring during the perimenstrual period and the local stimulus for angiogenesis. The aim of this study was to investigate the effects of hypoxic stress on the regulation of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1/CXCL12), and the potential role of hypoxia-inducible factor-1α (HIF-1α) in the endometrium. Human endometrial stromal cells (ESCs, n= 22 samples) were studied in vitro. ESCs were cultured under hypoxic and normoxic conditions and treated with cobalt chloride (CoCl₂; a hypoxia-mimicking agent) and/or echinomycin, a small-molecule inhibitor of HIF-1α activity. The mRNA levels and production of VEGF and SDF-1 were assessed by real-time PCR and ELISA, respectively. The HIF-1α protein levels were measured using western blot analysis. Hypoxia simultaneously induced the expression of mRNA and production of VEGF and attenuated the expression and production of SDF-1 from ESCs in a time-dependent manner. Similar changes were observed in the ESCs after stimulation with CoCl₂ in a dose-dependent manner. CoCl₂ significantly induced the expression of HIF-1α protein, and its highest expression was observed at 6 h. Echinomycin inhibited hypoxia-induced VEGF production without affecting the HIF-1α protein level and cell toxicity and had no effect on SDF-1 secretion (P hypoxic conditions that could influence angiogenesis in the human endometrium.

  9. Pigment epithelium-derived factor as a multifunctional regulator of wound healing

    Science.gov (United States)

    Wietecha, Mateusz S.; Król, Mateusz J.; Michalczyk, Elizabeth R.; Chen, Lin; Gettins, Peter G.

    2015-01-01

    During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate regulator is pigment epithelium-derived factor (PEDF), a secreted glycoprotein. PEDF is a potent antiangiogenic in models of pathological angiogenesis and a promising cancer and cardiovascular disease therapeutic, but little is known about its physiological function. To examine the roles of PEDF in physiological wound repair, we used a reproducible model of excisional skin wound healing in BALB/c mice. We show that PEDF is abundant in unwounded and healing skin, is produced primarily by dermal fibroblasts, binds to resident microvascular endothelial cells, and accumulates in dermal ECM and epidermis. PEDF transcript and protein levels were low during the inflammatory and proliferative phases of healing but increased in quantity and colocalization with microvasculature during wound resolution. Local antibody inhibition of endogenous PEDF delayed vessel regression and collagen maturation during the remodeling phase. Treatment of wounds with intradermal injections of exogenous, recombinant PEDF inhibited nascent angiogenesis by repressing endothelial proliferation, promoted vascular integrity and function, and increased collagen maturity. These results demonstrate that PEDF contributes to the resolution of healing wounds by causing regression of immature blood vessels and stimulating maturation of the vascular microenvironment, thus promoting a return to tissue homeostasis after injury. PMID:26163443

  10. Enhanced glucose tolerance in pancreatic-derived factor (PANDER knockout C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Shari L. Moak

    2014-11-01

    Full Text Available Pancreatic-derived factor (PANDER; also known as FAM3B is a uniquely structured protein strongly expressed within and secreted from the endocrine pancreas. PANDER has been hypothesized to regulate fasting and fed glucose homeostasis, hepatic lipogenesis and insulin signaling, and to serve a potential role in the onset or progression of type 2 diabetes (T2D. Despite having potentially pivotal pleiotropic roles in glycemic regulation and T2D, there has been limited generation of stable animal models for the investigation of PANDER function, and there are no models on well-established genetic murine backgrounds for T2D. Our aim was to generate an enhanced murine model to further elucidate the biological function of PANDER. Therefore, a pure-bred PANDER knockout C57BL/6 (PANKO-C57 model was created and phenotypically characterized with respect to glycemic regulation and hepatic insulin signaling. The PANKO-C57 model exhibited an enhanced metabolic phenotype, particularly with regard to enhanced glucose tolerance. Male PANKO-C57 mice displayed decreased fasting plasma insulin and C-peptide levels, whereas leptin levels were increased as compared with matched C57BL/6J wild-type mice. Despite similar peripheral insulin sensitivity between both groups, hepatic insulin signaling was significantly increased during fasting conditions, as demonstrated by increased phosphorylation of hepatic PKB/Akt and AMPK, along with mature SREBP-1 expression. Insulin stimulation of PANKO-C57 mice resulted in increased hepatic triglyceride and glycogen content as compared with wild-type C57BL/6 mice. In summary, the PANKO-C57 mouse represents a suitable model for the investigation of PANDER in multiple metabolic states and provides an additional tool to elucidate the biological function and potential role in T2D.

  11. Reversion of autocrine transformation by a dominant negative platelet-derived growth factor mutant.

    Science.gov (United States)

    Vassbotn, F S; Andersson, M; Westermark, B; Heldin, C H; Ostman, A

    1993-07-01

    A non-receptor-binding mutant of the platelet-derived growth factor (PDGF) A chain, PDGF-0, was generated by exchanging 7 amino acids in the sequence. The mutant chains formed dimers that were similar to wild-type PDGF-AA with regard to stability and rate of processing to the mature 30-kDa secreted forms. Moreover, the mutant chains formed disulfide-bonded heterodimers with the PDGF B chain in NIH 3T3 cells heterodimer underwent the same processing and secretion as PDGF-AB. Transfection of c-sis-expressing 3T3 cells with PDGF-0 significantly inhibited the transformed phenotype of these cells, as determined by the following criteria. (i) Compared with PDGF-0-negative clones, PDGF-0-producing clones showed a reverted morphology. (ii) Clones producing PDGF-0 grew more slowly than PDGF-0-negative clones, with a fivefold difference in cell number after 14 days in culture. (iii) The expression of PDGF-0 completely inhibited the ability of the c-sis-expressing 3T3 cells to form colonies in soft agar; this inhibition was overcome by the addition of recombinant PDGF-BB to the culture medium, showing that the lack of colony formation of these cells was not due to a general unresponsiveness to PDGF. The specific expression of a PDGF-0/PDGF wild-type heterodimer in COS cells revealed that the affinity of the mutant heterodimer for the PDGF alpha receptor was decreased by approximately 50-fold compared with that of PDGF-AA. Thus, we show that a non-receptor-binding PDGF A-chain mutant neutralizes in a trans-dominant manner the autocrine transforming potential of the c-sis/PDGF B chain by forming low-affinity heterodimers with wild-type PDGF chains. This method of specifically antagonizing the effect of PDGF may be useful in investigations of the role of PDGF in normal and pathological conditions.

  12. Electrically induced brain-derived neurotrophic factor release from Schwann cells.

    Science.gov (United States)

    Luo, Beier; Huang, Jinghui; Lu, Lei; Hu, Xueyu; Luo, Zhuojing; Li, Ming

    2014-07-01

    Regulating the production of brain-derived neurotrophic factor (BDNF) in Schwann cells (SCs) is critical for their application in traumatic nerve injury, neurodegenerative disorders, and demyelination disease in both central and peripheral nervous systems. The present study investigated the possibility of using electrical stimulation (ES) to activate SCs to release BDNF. We found that short-term ES was capable of promoting BDNF production from SCs, and the maximal BDNF release was achieved by ES at 6 V (3 Hz, 30 min). We further examined the involvement of intracellular calcium ions ([Ca2+]i) in the ES-induced BDNF production in SCs by pharmacological studies. We found that the ES-induced BDNF release required calcium influx through T-type voltage-gated calcium channel (VGCC) and calcium mobilization from internal calcium stores, including inositol triphosphate-sensitive stores and caffeine/ryanodine-sensitive stores. In addition, calcium-calmodulin dependent protein kinase IV (CaMK IV), mitogen-activated protein kinase (MAPK), and cAMP response element-binding protein (CREB) were found to play important roles in the ES-induced BDNF release from SCs. In conclusion, ES is capable of activating SCs to secrete BDNF, which requires the involvement of calcium influx through T-type VGCC and calcium mobilization from internal calcium stores. In addition, activation of CaMK IV, MAPK, and CREB were also involved in the ES-induced BDNF release. The findings indicate that ES can improve the neurotrophic ability in SCs and raise the possibility of developing electrically stimulated SCs as a source of cell therapy for nerve injury in both peripheral and central nervous systems. Copyright © 2014 Wiley Periodicals, Inc.

  13. Mechanism of hyperphagia contributing to obesity in brain-derived neurotrophic factor knockout mice.

    Science.gov (United States)

    Fox, E A; Biddinger, J E; Jones, K R; McAdams, J; Worman, A

    2013-01-15

    Global-heterozygous and brain-specific homozygous knockouts (KOs) of brain-derived neurotrophic factor (BDNF) cause late- and early-onset obesity, respectively, both involving hyperphagia. Little is known about the mechanism underlying this hyperphagia or whether BDNF loss from peripheral tissues could contribute to overeating. Since global-homozygous BDNF-KO is perinatal lethal, a BDNF-KO that spared sufficient brainstem BDNF to support normal health was utilized to begin to address these issues. Meal pattern and microstructure analyses suggested overeating of BDNF-KO mice was mediated by deficits in both satiation and satiety that resulted in increased meal size and frequency and implicated a reduction of vagal signaling from the gut to the brain. Meal-induced c-Fos activation in the nucleus of the solitary tract, a more direct measure of vagal afferent signaling, however, was not decreased in BDNF-KO mice, and thus was not consistent with a vagal afferent role. Interestingly though, meal-induced c-Fos activation was increased in the dorsal motor nucleus of the vagus nerve (DMV) of BDNF-KO mice. This could imply that augmentation of vago-vagal digestive reflexes occurred (e.g., accommodation), which would support increased meal size and possibly increased meal number by reducing the increase in intragastric pressure produced by a given amount of ingesta. Additionally, vagal sensory neuron number in BDNF-KO mice was altered in a manner consistent with the increased meal-induced activation of the DMV. These results suggest reduced BDNF causes satiety and satiation deficits that support hyperphagia, possibly involving augmentation of vago-vagal reflexes mediated by central pathways or vagal afferents regulated by BDNF levels. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Stromal cell-derived factor 1 regulates the actin organization of chondrocytes and chondrocyte hypertrophy.

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    Koichi Murata

    Full Text Available Stromal cell-derived factor 1 (SDF-1/CXCL12/PBSF plays important roles in the biological and physiological functions of haematopoietic and mesenchymal stem cells. This chemokine regulates the formation of multiple organ systems during embryogenesis. However, its roles in skeletal development remain unclear. Here we investigated the roles of SDF-1 in chondrocyte differentiation. We demonstrated that SDF-1 protein was expressed at pre-hypertrophic and hypertrophic chondrocytes in the newly formed endochondral callus of rib fracture as well as in the growth plate of normal mouse tibia by immunohistochemical analysis. Using SDF-1(-/- mouse embryo, we histologically showed that the total length of the whole humeri of SDF-1(-/- mice was significantly shorter than that of wild-type mice, which was contributed mainly by shorter hypertrophic and calcified zones in SDF-1(-/- mice. Actin cytoskeleton of hypertrophic chondrocytes in SDF-1(-/- mouse humeri showed less F-actin and rounder shape than that of wild-type mice. Primary chondrocytes from SDF-1(-/- mice showed the enhanced formation of philopodia and loss of F-actin. The administration of SDF-1 to primary chondrocytes of wild-type mice and SDF-1(-/- mice promoted the formation of actin stress fibers. Organ culture of embryonic metatarsals from SDF-1(-/- mice showed the growth delay, which was recovered by an exogenous administration of SDF-1. mRNA expression of type X collagen in metatarsals and in primary chondrocytes of SDF-1(-/- mouse embryo was down-regulated while the administration of SDF-1 to metatarsals recovered. These data suggests that SDF-1 regulates the actin organization and stimulates bone growth by mediating chondrocyte hypertrophy.

  15. Use of Brevibacillus choshinensis for the production of biologically active brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

    Angart, Phillip A; Carlson, Rebecca J; Thorwall, Sarah; Patrick Walton, S

    2017-07-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family critical for neuronal cell survival and differentiation, with therapeutic potential for the treatment of neurological disorders and spinal cord injuries. The production of recombinant, bioactive BDNF is not practical in most traditional microbial expression systems because of the inability of the host to correctly form the characteristic cystine-knot fold of BDNF. Here, we investigated Brevibacillus choshinensis as a suitable expression host for bioactive BDNF expression, evaluating the effects of medium type (2SY and TM), temperature (25 and 30 °C), and culture time (48-120 h). Maximal BDNF bioactivity (per unit mass) was observed in cultures grown in 2SY medium at extended times (96 h at 30 °C or >72 h at 25 °C), with resulting bioactivity comparable to that of a commercially available BDNF. For cultures grown in 2SY medium at 25 °C for 72 h, the condition that led to the greatest quantity of biologically active protein in the shortest culture time, we recovered 264 μg/L of BDNF. As with other microbial expression systems, BDNF aggregates did form in all culture conditions, indicating that while we were able to recover biologically active BDNF, further optimization of the expression system could yield still greater quantities of bioactive protein. This study provides confirmation that B. choshinensis is capable of producing biologically active BDNF and that further optimization of culture conditions could prove valuable in increasing BDNF yields.

  16. Complete spinal cord injury (SCI) transforms how brain derived neurotrophic factor (BDNF) affects nociceptive sensitization.

    Science.gov (United States)

    Huang, Yung-Jen; Lee, Kuan H; Grau, James W

    2017-02-01

    Noxious stimulation can induce a lasting increase in neural excitability within the spinal cord (central sensitization) that can promote pain and disrupt adaptive function (maladaptive plasticity). Brain-derived neurotrophic factor (BDNF) is known to regulate the development of plasticity and has been shown to impact the development of spinally-mediated central sensitization. The latter effect has been linked to an alteration in GABA-dependent inhibition. Prior studies have shown that, in spinally transected rats, exposure to regular (fixed spaced) stimulation can counter the development of maladaptive plasticity and have linked this effect to an up-regulation of BDNF. Here it is shown that application of the irritant capsaicin to one hind paw induces enhanced mechanical reactivity (EMR) after spinal cord injury (SCI) and that the induction of this effect is blocked by pretreatment with fixed spaced shock. This protective effect was eliminated if rats were pretreated with the BDNF sequestering antibody TrkB-IgG. Intrathecal (i.t.) application of BDNF prevented, but did not reverse, capsaicin-induced EMR. BDNF also attenuated cellular indices (ERK and pERK expression) of central sensitization after SCI. In uninjured rats, i.t. BDNF enhanced, rather than attenuated, capsaicin-induced EMR and ERK/pERK expression. These opposing effects were related to a transformation in GABA function. In uninjured rats, BDNF reduced membrane-bound KCC2 and the inhibitory effect of the GABA A agonist muscimol. After SCI, BDNF increased KCC2 expression, which would help restore GABAergic inhibition. The results suggest that SCI transforms how BDNF affects GABA function and imply that the clinical usefulness of BDNF will depend upon the extent of fiber sparing. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Learned helplessness is independent of levels of brain-derived neurotrophic factor in the hippocampus.

    Science.gov (United States)

    Greenwood, B N; Strong, P V; Foley, T E; Thompson, R S; Fleshner, M

    2007-02-23

    Reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus have been implicated in human affective disorders and behavioral stress responses. The current studies examined the role of BDNF in the behavioral consequences of inescapable stress, or learned helplessness. Inescapable stress decreased BDNF mRNA and protein in the hippocampus of sedentary rats. Rats allowed voluntary access to running wheels for either 3 or 6 weeks prior to exposure to stress were protected against stress-induced reductions of hippocampal BDNF protein. The observed prevention of stress-induced deceases in BDNF, however, occurred in a time course inconsistent with the prevention of learned helplessness by wheel running, which is evident following 6 weeks, but not 3 weeks, of wheel running. BDNF suppression in physically active rats was produced by administering a single injection of the selective serotonin reuptake inhibitor fluoxetine (10 mg/kg) just prior to stress. Despite reduced levels of hippocampal BDNF mRNA following stress, physically active rats given the combination of fluoxetine and stress remained resistant against learned helplessness. Sedentary rats given both fluoxetine and stress still demonstrated typical learned helplessness behaviors. Fluoxetine by itself reduced BDNF mRNA in sedentary rats only, but did not affect freezing or escape learning 24 h later. Finally, bilateral injections of BDNF (1 mug) into the dentate gyrus prior to stress prevented stress-induced reductions of hippocampal BDNF but did not prevent learned helplessness in sedentary rats. These data indicate that learned helplessness behaviors are independent of the presence or absence of hippocampal BDNF because blocking inescapable stress-induced BDNF suppression does not always prevent learned helplessness, and learned helplessness does not always occur in the presence of reduced BDNF. Results also suggest that the prevention of stress-induced hippocampal BDNF suppression is not

  18. Stromal cell-derived factor 1 regulates the actin organization of chondrocytes and chondrocyte hypertrophy.

    Science.gov (United States)

    Murata, Koichi; Kitaori, Toshiyuki; Oishi, Shinya; Watanabe, Naoki; Yoshitomi, Hiroyuki; Tanida, Shimei; Ishikawa, Masahiro; Kasahara, Takashi; Shibuya, Hideyuki; Fujii, Nobutaka; Nagasawa, Takashi; Nakamura, Takashi; Ito, Hiromu

    2012-01-01

    Stromal cell-derived factor 1 (SDF-1/CXCL12/PBSF) plays important roles in the biological and physiological functions of haematopoietic and mesenchymal stem cells. This chemokine regulates the formation of multiple organ systems during embryogenesis. However, its roles in skeletal development remain unclear. Here we investigated the roles of SDF-1 in chondrocyte differentiation. We demonstrated that SDF-1 protein was expressed at pre-hypertrophic and hypertrophic chondrocytes in the newly formed endochondral callus of rib fracture as well as in the growth plate of normal mouse tibia by immunohistochemical analysis. Using SDF-1(-/-) mouse embryo, we histologically showed that the total length of the whole humeri of SDF-1(-/-) mice was significantly shorter than that of wild-type mice, which was contributed mainly by shorter hypertrophic and calcified zones in SDF-1(-/-) mice. Actin cytoskeleton of hypertrophic chondrocytes in SDF-1(-/-) mouse humeri showed less F-actin and rounder shape than that of wild-type mice. Primary chondrocytes from SDF-1(-/-) mice showed the enhanced formation of philopodia and loss of F-actin. The administration of SDF-1 to primary chondrocytes of wild-type mice and SDF-1(-/-) mice promoted the formation of actin stress fibers. Organ culture of embryonic metatarsals from SDF-1(-/-) mice showed the growth delay, which was recovered by an exogenous administration of SDF-1. mRNA expression of type X collagen in metatarsals and in primary chondrocytes of SDF-1(-/-) mouse embryo was down-regulated while the administration of SDF-1 to metatarsals recovered. These data suggests that SDF-1 regulates the actin organization and stimulates bone growth by mediating chondrocyte hypertrophy.

  19. Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation.

    Science.gov (United States)

    Gomez-Pinilla, F; Zhuang, Y; Feng, J; Ying, Z; Fan, G

    2011-02-01

    We have evaluated the possibility that the action of voluntary exercise on the regulation of brain-derived neurotrophic factor (BDNF), a molecule important for rat hippocampal learning, could involve mechanisms of epigenetic regulation. We focused the studies on the Bdnf promoter IV, as this region is highly responsive to neuronal activity. We have found that exercise stimulates DNA demethylation in Bdnf promoter IV, and elevates levels of activated methyl-CpG-binding protein 2, as well as BDNF mRNA and protein in the rat hippocampus. Chromatin immunoprecipitation assay showed that exercise increases acetylation of histone H3, and protein assessment showed that exercise elevates the ratio of acetylated :total for histone H3 but had no effects on histone H4 levels. Exercise also reduces levels of the histone deacetylase 5 mRNA and protein implicated in the regulation of the Bdnf gene [N.M. Tsankova et al. (2006)Nat. Neurosci., 9, 519-525], but did not affect histone deacetylase 9. Exercise elevated the phosphorylated forms of calcium/calmodulin-dependent protein kinase II and cAMP response element binding protein, implicated in the pathways by which neural activity influences the epigenetic regulation of gene transcription, i.e. Bdnf. These results showing the influence of exercise on the remodeling of chromatin containing the Bdnf gene emphasize the importance of exercise on the control of gene transcription in the context of brain function and plasticity. Reported information about the impact of a behavior, inherently involved in the daily human routine, on the epigenome opens exciting new directions and therapeutic opportunities in the war against neurological and psychiatric disorders. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  20. Involvement of Endogenous Brain-Derived Neurotrophic Factor in Hypothalamic-Pituitary-Adrenal Axis Activity.

    Science.gov (United States)

    Naert, G; Zussy, C; Tran Van Ba, C; Chevallier, N; Tang, Y-P; Maurice, T; Givalois, L

    2015-11-01

    Brain-derived neurotrophic factor (BDNF) appears to be highly involved in hypothalamic-pituitary-adrenal (HPA) axis regulation during adulthood, playing an important role in homeostasis maintenance. The present study aimed to determine the involvement of BDNF in HPA axis activity under basal and stress conditions via partial inhibition of this endogenous neurotrophin. Experiments were conducted in rats and mice with two complementary approaches: (i) BDNF knockdown with stereotaxic delivery of BDNF-specific small interfering RNA (siRNA) into the lateral ventricle of adult male rats and (ii) genetically induced knockdown (KD) of BDNF expression specifically in the central nervous system during the first ontogenesis in mice (KD mice). Delivery of siRNA in the rat brain decreased BDNF levels in the hippocampus (-31%) and hypothalamus (-35%) but not in the amygdala, frontal cortex and pituitary. In addition, siRNA induced no change of the basal HPA axis activity. BDNF siRNA rats exhibited decreased BDNF levels and concomitant altered adrenocortoctrophic hormone (ACTH) and corticosterone responses to restraint stress, suggesting the involvement of BDNF in the HPA axis adaptive response to stress. In KD mice, BDNF levels in the hippocampus and hypothalamus were decreased by 20% in heterozygous and by 60% in homozygous animals compared to wild-type littermates. Although, in heterozygous KD mice, no significant change was observed in the basal levels of plasma ACTH and corticosterone, both hormones were significantly increased in homozygous KD mice, demonstrating that robust cerebral BDNF inhibition (60%) is necessary to affect basal HPA axis activity. All of these results in both rats and mice demonstrate the involvement and importance of a robust endogenous pool of BDNF in basal HPA axis regulation and the pivotal function of de novo BDNF synthesis in the establishment of an adapted response to stress. © 2015 British Society for Neuroendocrinology.

  1. Assessment of Brain Derived Neurotrophic Factor in hair to study stress responses: A pilot investigation.

    Science.gov (United States)

    Harb, H; González-de-la-Vara, M; Thalheimer, L; Klein, U; Renz, H; Rose, M; Kruse, J; Potaczek, D P; Peters, E M J

    2017-12-01

    To study pathogenic stress-effects in health and disease, it is paramount to define easy access parameters for non-invasive analysis of biological change in response to stress. Hair samples successfully provide this access for the study of hypothalamus-pituitary-adrenal axis (HPA) changes. In this study, we assess the hair expression and corresponding epigenetic changes of a neurotrophin essential for autonomic nervous system function and mental health: brain derived neurotrophic factor (BDNF). In three independent studies in healthy academic volunteers (study I: German students, N=36; study II, German academic population sample, N=28; study III: Mexican students, N=115), BDNF protein expression or BDNF gene (BDNF) histone acetylation was determined. Simultaneously, mental distress and distress-associated somatic complaints were assessed by self-report. In study I, we found a negative correlation between hair-BDNF protein level and hair-cortisol as well as between hair-BDNF and somatic complaints, while hair-cortisol correlated positively with mental distress. In study II, we found a negative correlation between H4 histone acetylation at the BDNF gene P4-promoter and somatic complaints. Regression analysis confirmed confounder stability of associations in both studies. In study III, we confirmed study I and found lower hair-BDNF protein level in volunteers with high somatic complaints, who also reported higher mental distress during the end of term exams. The results indicate that BDNF protein levels can be detected in clipped hair and are associated with somatic complaints and stress in life. In addition, we concluded that plucked hair can provide material for the study of epigenetic changes in stress-affected tissues. These tools can prove valuable for future studies on distress, both under experimental and field conditions. Copyright © 2017. Published by Elsevier Ltd.

  2. Hepatoma-derived growth factor and nucleolin exist in the same ribonucleoprotein complex

    Directory of Open Access Journals (Sweden)

    Bremer Stephanie

    2013-01-01

    Full Text Available Abstract Background Hepatoma-derived growth factor (HDGF is a protein which is highly expressed in a variety of tumours. HDGF has mitogenic, angiogenic, neurotrophic and antiapoptotic activity but the molecular mechanisms by which it exerts these activities are largely unknown nor has its biological function in tumours been elucidated. Mass spectrometry was performed to analyse the HDGFStrep-tag interactome. By Pull–down-experiments using different protein and nucleic acid constructs the interaction of HDGF and nucleolin was investigated further. Results A number of HDGFStrep-tag copurifying proteins were identified which interact with RNA or are involved in the cellular DNA repair machinery. The most abundant protein, however, copurifying with HDGF in this approach was nucleolin. Therefore we focus on the characterization of the interaction of HDGF and nucleolin in this study. We show that expression of a cytosolic variant of HDGF causes a redistribution of nucleolin into the cytoplasm. Furthermore, formation of HDGF/nucleolin complexes depends on bcl-2 mRNA. Overexpression of full length bcl-2 mRNA increases the number of HDGF/nucleolin complexes whereas expression of only the bcl-2 coding sequence abolishes interaction completely. Further examination reveals that the coding sequence of bcl-2 mRNA together with either the 5′ or 3′ UTR is sufficient for formation of HDGF/nucleolin complexes. When bcl-2 coding sequence within the full length cDNA is replaced by a sequence coding for secretory alkaline phosphatase complex formation is not enhanced. Conclusion The results provide evidence for the existence of HDGF and nucleolin containing nucleoprotein complexes which formation depends on the presence of specific mRNAs. The nature of these RNAs and other components of the complexes should be investigated in future.

  3. Skewness and flatness factors of the longitudinal velocity derivative in wall-bounded flows

    Science.gov (United States)

    Djenidi, Lyazid; Antonia, Robert A.; Talluru, Murali K.; Abe, Hiroyuki

    2017-06-01

    Hot-wire measurements are carried out in turbulent boundary layers over smooth and rough walls in order the assess the behavior of the skewness (S ) and flatness (F ) factors of the longitudinal velocity derivative as y , the distance from the wall, increases. The measurements are complemented by direct numerical simulations of a smooth wall turbulent channel flow. It is observed that, as the distance to the wall increases, S and F vary significantly before approaching a constant in the outer layer of the boundary layer. Further, S and F exhibit a nontrivial dependence on the Taylor microscale Reynolds number (Reλ). For example, in the region below about 0.2 δ (δ is the boundary layer thickness) where Reλ varies significantly, S and F strongly vary with Reλ and can be multivalued at a given Reλ. In the outer region, between 0.3 δ and 0.6 δ , S , F , and Reλ remain approximately constant. The channel flow direct numerical simulation data for S and F exhibit a similar behavior. These results point to the ambiguity that can arise when assessing the Reλ dependence of S and F in wall shear flows. In particular, the multivaluedness of S and F can lead to erroneous conclusions if y /δ is known only poorly, as is the case for the atmospheric shear layer (ASL). If the laboratory turbulent boundary layer is considered an adequate surrogate to the neutral ASL, then the behavior of S and F in the ASL is expected to be similar to that reported here.

  4. Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study.

    Science.gov (United States)

    Ryan, K M; Glaviano, A; O'Donovan, S M; Kolshus, E; Dunne, R; Kavanagh, A; Jelovac, A; Noone, M; Tucker, G M; Dunn, M J; McLoughlin, D M

    2017-03-28

    Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression.

  5. Decreased plasma concentrations of brain-derived neurotrophic factor (BDNF) in patients with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Podfigurna-Stopa, Agnieszka; Casarosa, Elena; Luisi, Michele; Czyzyk, Adam; Meczekalski, Blazej; Genazzani, Andrea Riccardo

    2013-09-01

    Functional hypothalamic amenorrhea (FHA) is a non organic, secondary amenorrhea related to gonadotropin-releasing hormone pulsatile secretion impairment. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays an important role in the growth, development, maintenance and function of several neuronal systems. The aim of the study was the evaluation of plasma BDNF concentrations in patients with the diagnosis of FHA. We studied 85 subjects diagnosed with FHA who were compared with 10 healthy, eumenorrheic controls with normal body mass index. Plasma BDNF and serum luteinizing hormone, follicle-stimulating hormone and estradiol (E2) concentrations were measured by immunoenzymatic method (enzyme-linked immunosorbent assay). Significantly lower concentration of plasma BDNF was found in FHA patients (196.31 ± 35.26 pg/ml) in comparison to healthy controls (407.20 ± 25.71 pg/ml; p < 0.0001). In the control group, there was a strong positive correlation between plasma BDNF and serum E2 concentrations (r = 0.92, p = 0.0001) but in FHA group it was not found. Role of BDNF in FHA is not yet fully understood. There could be found studies concerning plasma BDNF concentrations in humans and animals in the literature. However, our study is one of the first projects which describes decreased plasma BDNF concentration in patients with diagnosed FHA. Therefore, further studies on BDNF in FHA should clarify the role of this peptide.

  6. Platelet-derived growth factor regulates K-Cl cotransport in vascular smooth muscle cells.

    Science.gov (United States)

    Zhang, Jing; Lauf, Peter K; Adragna, Norma C

    2003-03-01

    Platelet-derived growth factor (PDGF), a potent serum mitogen for vascular smooth muscle cells (VSMCs), plays an important role in membrane transport regulation and in atherosclerosis. K-Cl cotransport (K-Cl COT/KCC), the coupled-movement of K and Cl, is involved in ion homeostasis. VSMCs possess K-Cl COT activity and the KCC1 and KCC3 isoforms. Here, we report on the effect of PDGF on K-Cl COT activity and mRNA expression in primary cultures of rat VSMCs. K-Cl COT was determined as the Cl-dependent Rb influx and mRNA expression by semiquantitative RT-PCR. Twenty four-hour serum deprivation inhibited basal K-Cl COT activity. Addition of PDGF increased total protein content and K-Cl COT activity in a time-dependent manner. PDGF activated K-Cl COT in a dose-dependent manner, both acutely (10 min) and chronically (12 h). AG-1296, a selective inhibitor of the PDGF receptor tyrosine kinase, abolished these effects. Actinomycin D and cycloheximide had no effect on the acute PDGF activation of K-Cl COT, suggesting posttranslational regulation by the drug. Furthermore, PDGF increased KCC1 and decreased KCC3 mRNA expression in a time-dependent manner. These results indicate that chronic activation of K-Cl COT activity by PDGF may involve regulation of the two KCC mRNA isoforms, with KCC1 playing a dominant role in the mechanism of PDGF-mediated activation.

  7. Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome.

    Science.gov (United States)

    Subedi, Lochan; Huang, Hong; Pant, Amrita; Westgate, Philip M; Bada, Henrietta S; Bauer, John A; Giannone, Peter J; Sithisarn, Thitinart

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS. To compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS. This is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS. 67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p  = 0.028). Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group ( p  = 0.04). There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p  = 0.47). There was no correlation between the BDNF levels and length of hospital stay ( p  = 0.68) among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p  = 0.045). Plasma BDNF level was significantly increased in NAS infants

  8. Effect of brain- and tumor-derived connective tissue growth factor on glioma invasion.

    Science.gov (United States)

    Edwards, Lincoln A; Woolard, Kevin; Son, Myung Jin; Li, Aiguo; Lee, Jeongwu; Ene, Chibawanye; Mantey, Samuel A; Maric, Dragan; Song, Hua; Belova, Galina; Jensen, Robert T; Zhang, Wei; Fine, Howard A

    2011-08-03

    Tumor cell invasion is the principal cause of treatment failure and death among patients with malignant gliomas. Connective tissue growth factor (CTGF) has been previously implicated in cancer metastasis and invasion in various tumors. We explored the mechanism of CTGF-mediated glioma cell infiltration and examined potential therapeutic targets. Highly infiltrative patient-derived glioma tumor-initiating or tumor stem cells (TIC/TSCs) were harvested and used to explore a CTGF-induced signal transduction pathway via luciferase reporter assays, chromatin immunoprecipitation (ChIP), real-time polymerase chain reaction, and immunoblotting. Treatment of TIC/TSCs with small-molecule inhibitors targeting integrin β1 (ITGB1) and the tyrosine kinase receptor type A (TrkA), and short hairpin RNAs targeting CTGF directly were used to reduce the levels of key protein components of CTGF-induced cancer infiltration. TIC/TSC infiltration was examined in real-time cell migration and invasion assays in vitro and by immunohistochemistry and in situ hybridization in TIC/TSC orthotopic xenograft mouse models (n = 30; six mice per group). All statistical tests were two-sided. Treatment of TIC/TSCs with CTGF resulted in CTGF binding to ITGB1-TrkA receptor complexes and nuclear factor kappa B (NF-κB) transcriptional activation as measured by luciferase reporter assays (mean relative luciferase activity, untreated vs CTGF(200 ng/mL): 0.53 vs 1.87, difference = 1.34, 95% confidence interval [CI] = 0.69 to 2, P < .001). NF-κB activation resulted in binding of ZEB-1 to the E-cadherin promoter as demonstrated by ChIP analysis with subsequent E-cadherin suppression (fold increase in ZEB-1 binding to the E-cadherin promoter region: untreated + ZEB-1 antibody vs CTGF(200 ng/mL) + ZEB-1 antibody: 1.5 vs 6.4, difference = 4.9, 95% CI = 4.8 to 5.0, P < .001). Immunohistochemistry and in situ hybridization revealed that TrkA is selectively expressed in the most infiltrative glioma cells in situ

  9. Gc-protein-derived macrophage activating factor counteracts the neuronal damage induced by oxaliplatin.

    Science.gov (United States)

    Morucci, Gabriele; Branca, Jacopo J V; Gulisano, Massimo; Ruggiero, Marco; Paternostro, Ferdinando; Pacini, Alessandra; Di Cesare Mannelli, Lorenzo; Pacini, Stefania

    2015-02-01

    Oxaliplatin-based regimens are effective in metastasized advanced cancers. However, a major limitation to their widespread use is represented by neurotoxicity that leads to peripheral neuropathy. In this study we evaluated the roles of a proven immunotherapeutic agent [Gc-protein-derived macrophage activating factor (GcMAF)] in preventing or decreasing oxaliplatin-induced neuronal damage and in modulating microglia activation following oxaliplatin-induced damage. The effects of oxaliplatin and of a commercially available formula of GcMAF [oleic acid-GcMAF (OA-GcMAF)] were studied in human neurons (SH-SY5Y cells) and in human microglial cells (C13NJ). Cell density, morphology and viability, as well as production of cAMP and expression of vascular endothelial growth factor (VEGF), markers of neuron regeneration [neuromodulin or growth associated protein-43 (Gap-43)] and markers of microglia activation [ionized calcium binding adaptor molecule 1 (Iba1) and B7-2], were determined. OA-GcMAF reverted the damage inflicted by oxaliplatin on human neurons and preserved their viability. The neuroprotective effect was accompanied by increased intracellular cAMP production, as well as by increased expression of VEGF and neuromodulin. OA-GcMAF did not revert the effects of oxaliplatin on microglial cell viability. However, it increased microglial activation following oxaliplatin-induced damage, resulting in an increased expression of the markers Iba1 and B7-2 without any concomitant increase in cell number. When neurons and microglial cells were co-cultured, the presence of OA-GcMAF significantly counteracted the toxic effects of oxaliplatin. Our results demonstrate that OA-GcMAF, already used in the immunotherapy of advanced cancers, may significantly contribute to neutralizing the neurotoxicity induced by oxaliplatin, at the same time possibly concurring to an integrated anticancer effect. The association between these two powerful anticancer molecules would probably produce

  10. Pulling the Trigger or Not: Factors Affecting Behavior of Initiating a Position in Derivatives Markets

    NARCIS (Netherlands)

    Pennings, J.M.E.

    2002-01-01

    The behavior of managers in initiating a derivatives market position brings to the surface an interesting phenomenon: sometimes managers initiate a position in derivatives markets (i.e., futures and options markets) and sometimes they do not, even though the price volatility of the underlying asset

  11. Combination effects of epidermal growth factor and glial cell line-derived neurotrophic factor on the in vitro developmental potential of porcine oocytes

    DEFF Research Database (Denmark)

    Valleh, Mehdi Vafaye; Rasmussen, Mikkel Aabech; Hyttel, Poul

    2016-01-01

    of improving this issue, the single and combined effects of epidermal growth factor (EGF) and glial cell line-derived neurotrophic factor (GDNF) on oocyte developmental competence were investigated. Porcine cumulus–oocyte cell complexes (COCs) were matured in serum-free medium supplemented with EGF (0, 10...... with the combination of EGF and GDNF was shown to significantly improve oocyte competence in terms of blastocyst formation, blastocyst cell number and blastocyst hatching rate (P

  12. Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis

    OpenAIRE

    Takagi, Satoshi; Takemoto, Ai; Takami, Miho; Oh-hara, Tomoko; Fujita, Naoya

    2014-01-01

    The interactions of tumor cells with platelets contribute to the progression of tumor malignancy, and the expression levels of platelet aggregation-inducing factors positively correlate with the metastatic potential of osteosarcoma cells. However, it is unclear how tumor-platelet interaction contributes to the proliferation of osteosarcomas. We report here that osteosarcoma-platelet interactions induce the release of platelet-derived growth factor (PDGF) from platelets, which promotes the pro...

  13. Corallocins A-C, Nerve Growth and Brain-Derived Neurotrophic Factor Inducing Metabolites from the Mushroom Hericium coralloides.

    Science.gov (United States)

    Wittstein, Kathrin; Rascher, Monique; Rupcic, Zeljka; Löwen, Eduard; Winter, Barbara; Köster, Reinhard W; Stadler, Marc

    2016-09-23

    Three new natural products, corallocins A-C (1-3), along with two known compounds were isolated from the mushroom Hericium coralloides. Their benzofuranone and isoindolinone structures were elucidated by spectral methods. All corallocins induced nerve growth factor and/or brain-derived neurotrophic factor expression in human 1321N1 astrocytes. Furthermore, corallocin B showed antiproliferative activity against HUVEC and human cancer cell lines MCF-7 and KB-3-1.

  14. Tissue Factor-Expressing Tumor-Derived Extracellular Vesicles Activate Quiescent Endothelial Cells via Protease-Activated Receptor-1

    Directory of Open Access Journals (Sweden)

    Sara P. Y. Che

    2017-11-01

    Full Text Available Tissue factor (TF-expressing tumor-derived extracellular vesicles (EVs can promote metastasis and pre-metastatic niche formation, but the mechanisms by which this occurs remain largely unknown. We hypothesized that generation of activated factor X (FXa by TF expressed on tumor-derived EV could activate protease-activated receptors (PARs on non-activated endothelial cells to induce a pro-adhesive and pro-inflammatory phenotype. We obtained EV from TF-expressing breast (MDA-MB-231 and pancreatic (BxPC3 and Capan-1 tumor cell lines. We measured expression of E-selectin and secretion of interleukin-8 (IL-8 in human umbilical vein endothelial cells after exposure to EV and various immunologic and chemical inhibitors of TF, FXa, PAR-1, and PAR-2. After 6 h of exposure to tumor-derived EV (pretreated with factor VIIa and FX in vitro, endothelial cells upregulated E-selectin expression and secreted IL-8. These changes were decreased with an anti-TF antibody, FXa inhibitors (FPRCK and EGRCK, and PAR-1 antagonist (E5555, demonstrating that FXa generated by TF-expressing tumor-derived EV was signaling through endothelial PAR-1. Due to weak constitutive PAR-2 expression, these endothelial responses were not induced by a PAR-2 agonist peptide (SLIGKV and were not inhibited by a PAR-2 antagonist (FSLLRY after exposure to tumor-derived EV. In conclusion, we found that TF-expressing cancer-derived EVs activate quiescent endothelial cells, upregulating E-selectin and inducing IL-8 secretion through generation of FXa and cleavage of PAR-1. Conversion of resting endothelial cells to an activated phenotype by TF-expressing cancer-derived EV could promote cancer metastases.

  15. Promotion of seminomatous tumors by targeted overexpression of glial cell line-derived neurotrophic factor in mouse testis

    NARCIS (Netherlands)

    Meng, X.; de rooij, D. G.; Westerdahl, K.; Saarma, M.; Sariola, H.

    2001-01-01

    We show with transgenic mice that targeted overexpression of glial cell line-derived neurotrophic factor (GDNF) in undifferentiated spermatogonia promotes malignant testicular tumors, which express germ-cell markers. The tumors are invasive and contain aneuploid cells, but no distant metastases have

  16. Effect of platelet-derived growth factor-BB on bone formation in calvarial defects: an experimental study in rabbits

    DEFF Research Database (Denmark)

    Vikjaer, D; Blom, S; Hjørting-Hansen, E

    1997-01-01

    The effect of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) on bone healing was examined in calvarial defects in rabbits. Bicortical circular (critical size) defects were prepared in the calvarial bone of 16 rabbits. The defects were closed on the dural side and covered externally...

  17. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation

    Directory of Open Access Journals (Sweden)

    Zhong-jun Zhang

    2015-01-01

    Full Text Available Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10 6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

  18. Chronic depression is associated with a pronounced decrease in serum brain-derived neurotrophic factor over time

    NARCIS (Netherlands)

    Bus, B.A.A.; Molendijk, M.L.; Tendolkar, I.; Penninx, B.W.J.H.; Prickaerts, J.; Elzinga, B.M.; Voshaar, R.C.O.

    2015-01-01

    One of the leading neurobiological hypotheses on depression states that decreased expression of brain-derived neurotrophic factor (BDNF) contributes to depression. This is supported by consistent findings of low serum BDNF levels in depressed patients compared with non-depressed controls. Whereas it

  19. Developmental Thyroid Hormone Insufficiency Reduces Expression of Brain-Derived Neurotrophic Factor (BDNF) in Adults But Not in Neonates

    Science.gov (United States)

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for many developmental and physiological aspects of CNS function. Severe hypothyroidism in the early neonatal period results in developmental and cognitive impairments and reductions in mRNA and protein expressio...

  20. Platelet-derived growth factor receptors in the human central nervous system : autoradiographic distribution and receptor densities in multiple sclerosis

    NARCIS (Netherlands)

    De Keyser, J; Wilczak, N

    1997-01-01

    Platelet derived growth factor (PDGF) receptors were studied in postmortem adult human brain and cervical spinal cord using autoradiography with human recombinant I-125-PDGF-BB. PDGF-BB binds to the three different dimers of PDGF receptors (alpha alpha, alpha beta and beta beta) PDGF receptors were

  1. Antidepressant Effects of Pharmacopuncture on Behavior and Brain-Derived Neurotrophic Factor (BDNF Expression in Chronic Stress Model of Mice

    Directory of Open Access Journals (Sweden)

    Yunna Kim

    2017-12-01

    Conclusion: HJ11 improves depressive-like behaviors in the stress-induced mouse model of depression, and the results indicate that the neuroprotective effect of HJ11, identified by brain-derived neurotrophic factor expression, may play a critical role in its antidepressant effect.

  2. Quantitative structure-activity relationships for the toxicity and bioconcentration factor of nitrobenzene derivatives towards the guppy (Poecilia reticulata)

    NARCIS (Netherlands)

    Deneer, J.W.; Sinnige, T.L.; Seinen, W.; Hermens, J.L.M.

    The acute toxicity and bioconcentration factor of a series of nitrobenzene derivatives was determined for the guppy. Toxicity is found to be determined by both hydrophobicity (expressed by the octanol/water partition coefficient) and rate of reduction of the nitro group (expressed by either

  3. Molecular cloning and functional characterization of the human platelet-derived growth factor alpha receptor gene promoter

    NARCIS (Netherlands)

    Afink, G. B.; Nistér, M.; Stassen, B. H.; Joosten, P. H.; Rademakers, P. J.; Bongcam-Rudloff, E.; van Zoelen, E. J.; Mosselman, S.

    1995-01-01

    Expression of the platelet-derived growth factor alpha receptor (PDGF alpha R) is strictly regulated during mammalian development and tumorigenesis. The molecular mechanisms involved in the specific regulation of PDGF alpha R expression are unknown, but transcriptional regulation of the PDGF alpha R

  4. Notch signaling regulates platelet-derived growth factor receptor-β expression in vascular smooth muscle cells

    NARCIS (Netherlands)

    Jin, S.; Hansson, E.M.; Tikka, S.; Lanner, F.; Sahlgren, C.; Farnebo, F.; Baumann, M.; Kalimo, H.; Lendahl, U.

    2008-01-01

    Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and dementia syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor

  5. Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: A role in depression

    NARCIS (Netherlands)

    Eisch, A.J.; Bolanos, C.A.; de Wit, J.; Simonak, R.D.; Pudiak, C.M.; Barrot, M.; Verhaagen, J.; Nestler, E.J.

    2003-01-01

    Background: Previous work has shown that brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), are involved in appetitive behavior. Here we show that BDNF in the ventral tegmental area-nucleus accumbens (VTA-NAc) pathway is also involved in the development of

  6. KOUAKOU BROU.mdi

    African Journals Online (AJOL)

    AISA

    efforts entrepris tend à améliorer le niveau alimentaire des enfants en relevant le niveau protidique. Ainsi, devant l'urgence des besoins, des organisations internatio- nales et locales ont suscité et favorisé dans divers pays des études visant à mettre au point des aliments composés infantiles riches en protéines et destinés ...

  7. TRAORE S..mdi

    African Journals Online (AJOL)

    AISA

    lte. Figure 2 : Régression entre la densité stomatique de la partie proximale de la face supérieure de la feuille et l'indice d'infection. Regression between stomata density of proximal area of upper surface of the limb and infection index. A : à 6 mois; B : à la floraison ; C : à la récolte. A: at 6 months; B: at flowering; C: at harvest ...

  8. MANGARA A.mdi

    African Journals Online (AJOL)

    AISA

    Asteraceae, figurent également parmi les familles les plus représentées dans la flore de la région du Gharb, zone agrumicole au Maroc. (Bensellam et al., 1997 ; Lastic, 1989). La prédominance des microphanérophytes. (26,79 %) dans cette étude, est également observée dans les palmeraies de La Mé (Traoré et al., 2005) ...

  9. KOUADIO K.mdi

    African Journals Online (AJOL)

    lara

    des conditions micro-climatiques (lumière, température, humidité, etc.) consécutives à la disparition de certains arbres engendrent, d'une part, une réactivation de la croissance du peuplement sur pied et, d'autre part, l'apparition de nouveaux individus dans la régénération naturelle. Les ouvertures dans le couvert forestier ...

  10. AMANE D.mdi

    African Journals Online (AJOL)

    lara

    SECHAGE. 2 - 3 jours. BROYAGE. FARINE. EAU. DECANTATION. 5 - 10 min. SURNAGEANT 1. DEPOT ET. FLOCULANT BLANC. SUBSTANCE. VISQUEUSE. EAU. PRECUISSON. 1 – 2 h. BARRIQUE. SUBSTANCE. VISQUEUSE. DECANTATION. 12 h. MELANGE. DECANTATION. 10 - 15 min. DEPOT. SURNAGEANT 2.

  11. article ndiayeoumar.MDI

    African Journals Online (AJOL)

    AISA

    L'alimentation hydrique est le principal facteur limitant la productivité du palmier à huile (Elaeis guineensis. Jacq.). Les réponses physiologiques des plantules, soumises à un déficit hydrique, ont été évaluées sous serre, dans des pots durant 4 mois. En vue d'identifier des critères discriminants au jeune âge pour une.

  12. ANGUI PASCAL.mdi

    African Journals Online (AJOL)

    USER

    l'amélioration des paramètres chimiques de deux types de sols. Il s'agit d'un ... et de dolomie (pour comparaison) pendant 30 j, en vue d'étudier leurs effets sur le pH, la capacité d'échange .... 5,5 n'ayant pas subi de coagulation-floculation.

  13. Deriving fuel-based emission factor thresholds to interpret heavy-duty vehicle roadside plume measurements.

    Science.gov (United States)

    Quiros, David C; Smith, Jeremy D; Ham, Walter A; Robertson, William H; Huai, Tao; Ayala, Alberto; Hu, Shaohua

    2018-04-13

    Remote sensing devices have been used for decades to measure gaseous emissions from individual vehicles at the roadside. Systems have also been developed that entrain diluted exhaust and can also measure particulate matter (PM) emissions. In 2015, the California Air Resources Board (CARB) reported that 8% of in-field diesel particulate filters (DPF) on heavy-duty (HD) vehicles were malfunctioning and emitted about 70% of total diesel PM emissions from the DPF-equipped fleet. A new high-emitter problem in the heavy-duty vehicle fleet had emerged. Roadside exhaust plume measurements reflect a snapshot of real-world operation, typically lasting several seconds. In order to relate roadside plume measurements to laboratory emission tests, we analyzed carbon dioxide (CO 2 ), oxides of nitrogen (NO X ), and PM emissions collected from four HD vehicles during several driving cycles on a chassis dynamometer. We examined the fuel-based emission factors corresponding to possible exceedances of emission standards as a function of vehicle power. Our analysis suggests that a typical HD vehicle will exceed the model year (MY) 2010 emission standards (of 0.2 g NO X /bhp-hr and 0.01 g PM/bhp-hr) by three times when fuel-based emission factors are 9.3 g NO X /kg fuel and 0.11 g PM/kg using the roadside plume measurement approach. Reported limits correspond to 99% confidence levels, which were calculated using the detection uncertainty of emissions analyzers, accuracy of vehicle power calculations, and actual emissions variability of fixed operational parameters. The PM threshold was determined for acceleration events between 0.47 and 1.4 mph/sec only, and the NO X threshold was derived from measurements where aftertreatment temperature was above 200°C. Anticipating a growing interest in real-world driving emissions, widespread implementation of roadside exhaust plume measurements as a compliment to in-use vehicle programs may benefit from expanding this analysis to a larger

  14. Estudio de viabilidad técnico-económico del vehículo con motor de aire comprimido MDI

    OpenAIRE

    Vizcarra Calle, Ricardo

    2006-01-01

    En el presente documento se estudia la viabilidad técnico-económica de los vehículos propulsados por el motor de aire comprimido MDI (Moteur Developpment International). Se inicia con una descripción general del vehículo así como el principio de funcionamiento del ciclo motor. Con un estudio termodinámico se cuantifica la cantidad de energía que disponen los vehículos con esta tecnología, valorando así su rendimiento termodinámico. Seguidamente se inicia una correlación de estudio...

  15. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, Keigo [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Takedachi, Masahide, E-mail: takedati@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Lee, Chun Man [Medical Center for Translational Research, Osaka University Hospital, Osaka (Japan); Okura, Hanayuki; Matsuyama, Akifumi [Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka (Japan); Kitamura, Masahiro; Murakami, Shinya [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan)

    2015-08-14

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

  16. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

    International Nuclear Information System (INIS)

    Sawada, Keigo; Takedachi, Masahide; Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki; Lee, Chun Man; Okura, Hanayuki; Matsuyama, Akifumi; Kitamura, Masahiro; Murakami, Shinya

    2015-01-01

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation

  17. Coagulation factor XI improves host defence during murine pneumonia-derived sepsis independent of factor XII activation

    NARCIS (Netherlands)

    Stroo, Ingrid; Zeerleder, Sacha; Ding, Chao; Luken, Brenda M.; Roelofs, Joris J. T. H.; de Boer, Onno J.; Meijers, Joost C. M.; Castellino, Francis J.; van 't Veer, Cornelis; van der Poll, Tom

    2017-01-01

    Bacterial pneumonia, the most common cause of sepsis, is associated with activation of coagulation. Factor XI (FXI), the key component of the intrinsic pathway, can be activated via factor XII (FXII), part of the contact system, or via thrombin. To determine whether intrinsic coagulation is involved

  18. Decreased serum levels of brain-derived neurotrophic factor in schizophrenic patients with deficit syndrome

    Directory of Open Access Journals (Sweden)

    Akyol ES

    2015-03-01

    Full Text Available Esra Soydas Akyol,1 Yakup Albayrak,2 Murat Beyazyüz,3 Nurkan Aksoy,4 Murat Kuloglu,5 Kenji Hashimoto6 1Deparment of Psychiatry, Yenimahalle Education and Research Hospital, Ankara, Turkey; 2Department of Psychiatry, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey; 3Department of Psychiatry, Biga State Hospital, Çanakkale, Turkey; 4Department of Biochemistry, Yenimahalle Education and Research Hospital, Ankara, Turkey; 5Department of Psychiatry, Faculty of Medicine, Akdeniz University, Antalya, Turkey; 6Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan Background: Brain-derived neurotrophic factor (BDNF is a well-established neurotrophin that plays a role in the pathophysiology of numerous psychiatric disorders. Many studies have investigated the serum BDNF levels in patients with schizophrenia. However, there are restricted data in the literature that compare the serum BDNF levels in patients with deficit and nondeficit syndromes. In this study, we aimed to compare the serum BDNF levels between schizophrenic patients with deficit or nondeficit syndrome and healthy controls.Methods: After fulfilling the inclusion and exclusion criteria, 58 patients with schizophrenia and 36 healthy controls were included in the study. The patients were grouped as deficit syndrome (N=23 and nondeficit syndrome (N=35 according to the Schedule for the Deficit Syndrome. Three groups were compared in terms of the sociodemographic and clinical variants and serum BDNF levels.Results: The groups were similar in terms of age, sex, body mass index, and smoking status. The serum BDNF levels in patients with deficit syndrome were significantly lower than those in healthy controls. In contrast, the serum BDNF levels in patients with nondeficit syndrome were similar to those in healthy controls.Conclusion: This study suggests that decreased BDNF levels may play a role in the pathophysio­logy of schizophrenic

  19. Treatment of AVN Using Autologous BM Stem Cells and Activated Platelet-Derived Growth Factor Concentrates.

    Science.gov (United States)

    Nandeesh, Nagaraj H; Janardhan, Kiranmayee; Subramanian, Vignesh; Ashtekar, Abhishek Bhushan; Srikruthi, Nandagiri; Koka, Prasad S; Deb, Kaushik

    Avascular Necrosis (AVN) of hip is a devastating condition seen in younger individuals. It is the ischemic death of the constituents of the bone cartilage of the hip. The femoral head (FH) is the most common site for AVN. It results from interruption of the normal blood flow to the FH that fits into the hip socket. Earlier studies using autologous bone marrow stem cell concentrate injections have shown encouraging results with average success rates. The current study was designed to improve significantly the cartilage regeneration and clinical outcome. Total of 48 patients underwent autologous bone marrow stem cell and activated platelet-rich plasma derived growth factor concentrate (PRP-GFC) therapy for early and advanced stages AVN of femoral head in a single multi-specialty center. The total treatment was divided into three phases. In the phase I, all the clinical diagnostic measurements such as magnetic resonance imaging (MRI), computed tomography (CT) etc. with respect to the AVN patients and bone marrow aspiration from posterior iliac spine from the patients were carried out. In the phase II, isolation of stem cells and preparation from the patients were performed. Subsequently, in phase III, the stem cells and PRP- GFCs were transplanted in the enrolled patients. Ninety three percent of the enrolled AVN patients showed marked enhancement in the hip bone joint space (more than 3mm) after combined stem cells and PRP-GFC treatment as evidenced by comparison of the pre- and post-treatment MRI data thus indicative of regeneration of cartilage. The treated patients showed significant improvement in their motor function, cartilage regrowth (3 to 10mm), and high satisfaction in the two-year follow-up. Combination of stem cell and PRP-GFC therapy has shown promising cartilage regeneration in 45 out of 48 patients of AVN. This study clearly demonstrates the safety and efficacy of this treatment. Larger numbers of patients need to be evaluated to better understand the

  20. Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome

    Directory of Open Access Journals (Sweden)

    Lochan Subedi

    2017-11-01

    Full Text Available BackgroundBrain-derived neurotrophic factor (BDNF is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS. Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS.ObjectiveTo compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS.MethodsThis is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS.Results67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p = 0.028. Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group (p = 0.04. There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p = 0.47. There was no correlation between the BDNF levels and length of hospital stay (p = 0.68 among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p = 0.045.ConclusionPlasma BDNF

  1. Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men.

    Science.gov (United States)

    Zoladz, J A; Pilc, A; Majerczak, J; Grandys, M; Zapart-Bukowska, J; Duda, K

    2008-12-01

    It is believed that brain derived neurotrophic factor (BDNF) plays an important role in neuronal growth, transmission, modulation and plasticity. Single bout of exercise can increase plasma BDNF concentration [BDNF](p) in humans. It was recently reported however, that elevated [BDNF](p) positively correlated with risk factors for metabolic syndrome and type 2 diabetes mellitus in middle age group of subjects. On the other hand it is well established that endurance training decreases the risk of diabetes and development of metabolic syndrome. In the present study we have examined the effect of 5 weeks of moderate intensity endurance training on the basal and the exercise induced changes in [BDNF](p) in humans. Thirteen young, healthy and physically active men (mean +/- S.E: age 22.7 +/- 0.5 yr, body height 180.2 +/- 1.7 cm, body weight 77.0 +/- 2.5 kg, V(O2max) 45.29 +/- 0.93 ml x kg-1 x min(-1)) performed a five week endurance cycling training program, composed mainly of moderate intensity bouts. Before training [BDNF]p at rest have amounted to 10.3 +/- 1.4 pg x ml(-1). No effect of a single maximal incremental cycling up to V(O2max) on its concentration was found (10.9 +/- 2.3 pg x ml(-1), P=0.74). The training resulted in a significant (P=0.01) increase in [BDNF]p at rest to 16.8 +/- 2.1 pg x ml(-1), as well as in significant (P=0.0002) exercise induced increase in the [BDNF](p) (10.9 +/- 2.3 pg x ml(-1) before training vs. 68.4 +/- 16.0 pg x ml(-1) after training). The training induced increase in resting [BDNF](p) was accompanied by a slight decrease in insulin resistance (P=0.25), calculated using the homeostatic model assessment version 2 (HOMA2-IR), amounting to 1.40 +/- 0.13 before and 1.15 +/- 0.13 after the training. Moreover, we have found that the basal [BDNF](p) in athletes (n=16) was significantly higher than in untrained subjects (n=13) (29.5 +/- 9.5 pg x ml(-1) vs. 10.3 +/- 1.4 pg x ml(-1), P=0.013). We have concluded that endurance training of

  2. Thyroxin treatment protects against white matter injury in the immature brain via brain-derived neurotrophic factor.

    Science.gov (United States)

    Hung, Pi-Lien; Huang, Chao-Ching; Huang, Hsiu-Mei; Tu, Dom-Gene; Chang, Ying-Chao

    2013-08-01

    Low level of thyroid hormone is a strong independent risk factor for white matter (WM) injury, a major cause of cerebral palsy, in preterm infants. Thyroxin upregulates brain-derived neurotrophic factor during development. We hypothesized that thyroxin protected against preoligodendrocyte apoptosis and WM injury in the immature brain via upregulation of brain-derived neurotrophic factor. Postpartum (P) day-7 male rat pups were exposed to hypoxic ischemia (HI) and intraperitoneally injected with thyroxin (T4; 0.2 mg/kg or 1 mg/kg) or normal saline immediately after HI at P9 and P11. WM damage was analyzed for myelin formation, axonal injury, astrogliosis, and preoligodendrocyte apoptosis. Neurotrophic factor expression was assessed by real-time polymerase chain reaction and immunohistochemistry. Neuromotor functions were measured using open-field locomotion (P11 and P21), inclined plane climbing (P11), and beam walking (P21). Intracerebroventricular injection of TrkB-Fc or systemic administration of 7,8-dihydroxyflavone was performed. On P11, the HI group had significantly lower blood T4 levels than the controls. The HI group showed ventriculomegaly and marked reduction of myelin basic protein immunoreactivities in the WM. T4 (1 mg/kg) treatment after HI markedly attenuated axonal injury, astrocytosis, and microgliosis, and increased preoligodendrocyte survival. In addition, T4 treatment significantly increased myelination and selectively upregulated brain-derived neurotrophic factor expression in the WM, and improved neuromotor deficits after HI. The protective effect of T4 on WM myelination and neuromotor performance after HI was significantly attenuated by TrkB-Fc. Systemic 7,8-dihydroxyflavone treatment ameliorated hypomyelination after HI injury. T4 protects against WM injury at both pathological and functional levels via upregulation of brain-derived neurotrophic factor-TrkB signaling in the immature brain.

  3. The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents

    DEFF Research Database (Denmark)

    Pedersen, Natascha Holbæk; Tarp, Jakob; Andersen, Lars Bo

    2017-01-01

    BACKGROUND AND OBJECTIVE: Cardiovascular disease and type 2 diabetes pose a global health burden. Therefore, clarifying the pathology of these risk factors is essential. Previous studies have found positive and negative associations between one or more cardiovascular risk factors and brain...... fitness (CRF), anthropometrics, pubertal status, blood pressure (BP), serum BDNF, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), blood glucose and insulin were measured. Information about alcohol consumption and socio-economic status was collected via questionnaires. Associations were...

  4. Transplant of stem cells derived from bone marrow and granulocytic growth factor in acute and chronic ischemic myocardiopathy

    International Nuclear Information System (INIS)

    Senior Juan M; Cuellar Francisco; Velasquez Oscar; Velasquez Margarita; Navas Claudia M; Ortiz Sergio; Delgado Juan A; Guillerrno, Blanco; Londono Juan L; Coronado Manuel A; Gomez Francisco; Alzate, Fernando Leon; Zuluaga Alejandra

    2007-01-01

    Recent studies have shown the safety and efficacy of the stem cells derived from bone marrow (BMC) implant with concomitant administration of stimulating factor of granulocyte colonies in patients with acute myocardial infarction with ST segment elevation and in chronic ischemic cardiopathy. An open prospective (before and after) design was made to evaluate the safety and efficacy of cell therapy associated to growth factor administration. The first experience with this kind of therapy is reported. Methodology: this is a 6 months follow-up report of patients with acute and chronic ischemic cardiopathy to who transplant of stem cells derived from bone marrow mobilized with granulocyte colonies growth stimulating factor via coronary arteries or epicardium was realized. Two groups of patients were included: Ten patients with anterior wall infarct and 2. Five patients with chronic ischemic cardiopathy, all with extensive necrosis demonstrated by absence of myocardial viability through nuclear medicine and ejection fraction of less than 40%. Results: significant improvement of ejection fraction from 29.44 ± 3.36 to 37.6 ± 5.3 with p<0.001 and decrease of ventricular systolic and diastolic volume without statistical significance (p =0.31 and 0.4 respectively) were demonstrated. Exercise capacity evidenced by increment in the six minutes test, exercise time and the MET number achieved, increased in a significant way. There were significant changes in the perfusion defect from the second follow-up month and no complications directly related to the stem cells derived from bone marrow transplant or the use of stimulating granulocyte colony factor were presented. Conclusions: this is the first experience of stem cells derived from bone marrow transplant associated to the administration of stimulating granulocyte growth colony factor in which recovery of left ventricular function was demonstrated, as well as improvement in exercise capacity and in the perfusion defect

  5. Derivation of Elastic Stress Concentration Factor Equations for Debris Fretting Flaws in Pressure Tubes of Pressurized Heavy Water Reactors

    International Nuclear Information System (INIS)

    Kim, Jong Sung; Oh, Young Jin

    2014-01-01

    If volumetric flaws such as bearing pad fretting flaws and debris fretting flaws are detected in the pressure tubes of pressurized heavy water reactors during in-service inspection, the initiation of fatigue cracks and delayed hydrogen cracking from the detected volumetric flaws shall be assessed by using elastic stress concentration factors in accordance with CSA N285.8-05. The CSA N285.8-05 presents only an approximate formula based on linear elastic fracture mechanics for the debris fretting flaw. In this study, an engineering formula considering the geometric characteristics of the debris fretting flaw in detail was derived using two-dimensional finite element analysis and Kinectrics, Inc.'s engineering procedure with slight modifications. Comparing the application results obtained using the derived formula with the three-dimensional finite element analysis results, it is found that the results obtained using the derived formula agree well with the results of the finite element analysis

  6. Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins

    Directory of Open Access Journals (Sweden)

    José Neptuno Rodríguez-López

    2013-07-01

    Full Text Available Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR, has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociation constants of the synthetic compounds and of the natural analogues were on the same order. Polyphenols with a catechin configuration were better DHFR inhibitors than those with an epicatechin configuration. Antiproliferative activity was also studied in cultured tumour cells, and the data showed that the activity of the novel derivatives was higher in catechin isomers. Derivatives with a hydroxyl group para on the ester-bonded gallate moiety presented a high in vitro binding to DHFR, but exhibited transport problems in cell culture due to ionization at physiologic pHs. The impact of the binding of catechins to serum albumin on their biological activity was also evaluated. The information provided in this study could be important for the design of novel medicinal active compounds derived from tea catechins. The data suggest that changes in their structure to avoid serum albumin interactions and to facilitate plasmatic membrane transport are essential for the intracellular functions of catechins.

  7. The Omitted Factor in Risk Management: Corporate Foreign Debt as an Alternative to Currency Derivatives

    DEFF Research Database (Denmark)

    Aabo, Tom

    Empirical surveys on exchange rate risk management in non-financial companies focus on the use of currency derivatives while omitting the use of corporate debt denominated in foreign currency ("foreign debt") even though the latter in risk management terms is identical to one or a series of forward...

  8. A generalized one-factor term structure model and pricing of interest rate derivative securities

    NARCIS (Netherlands)

    Jiang, George J.

    1997-01-01

    The purpose of this paper is to propose a nonparametric interest rate term structure model and investigate its implications on term structure dynamics and prices of interest rate derivative securities. The nonparametric spot interest rate process is estimated from the observed short-term interest

  9. Factors influencing the antifolate activity of synthetic tea-derived catechins.

    Science.gov (United States)

    Sáez-Ayala, Magalí; Fernández-Pérez, María Piedad; Chazarra, Soledad; Mchedlishvili, Nani; Tárraga-Tomás, Alberto; Rodríguez-López, José Neptuno

    2013-07-16

    Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR), has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociation constants of the synthetic compounds and of the natural analogues were on the same order. Polyphenols with a catechin configuration were better DHFR inhibitors than those with an epicatechin configuration. Antiproliferative activity was also studied in cultured tumour cells, and the data showed that the activity of the novel derivatives was higher in catechin isomers. Derivatives with a hydroxyl group para on the ester-bonded gallate moiety presented a high in vitro binding to DHFR, but exhibited transport problems in cell culture due to ionization at physiologic pHs. The impact of the binding of catechins to serum albumin on their biological activity was also evaluated. The information provided in this study could be important for the design of novel medicinal active compounds derived from tea catechins. The data suggest that changes in their structure to avoid serum albumin interactions and to facilitate plasmatic membrane transport are essential for the intracellular functions of catechins.

  10. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Ribeiro-Resende Victor

    2012-07-01

    Full Text Available Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC, satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2 is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS. Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL region of the lumbar spinal cord (LSC in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

  11. Effect of interpolation error in pre-processing codes on calculations of self-shielding factors and their temperature derivatives

    International Nuclear Information System (INIS)

    Ganesan, S.; Gopalakrishnan, V.; Ramanadhan, M.M.; Cullan, D.E.

    1986-01-01

    We investigate the effect of interpolation error in the pre-processing codes LINEAR, RECENT and SIGMA1 on calculations of self-shielding factors and their temperature derivatives. We consider the 2.0347 to 3.3546 keV energy region for 238 U capture, which is the NEACRP benchmark exercise on unresolved parameters. The calculated values of temperature derivatives of self-shielding factors are significantly affected by interpolation error. The sources of problems in both evaluated data and codes are identified and eliminated in the 1985 version of these codes. This paper helps to (1) inform code users to use only 1985 versions of LINEAR, RECENT, and SIGMA1 and (2) inform designers of other code systems where they may have problems and what to do to eliminate their problems. (author)

  12. Effect of interpolation error in pre-processing codes on calculations of self-shielding factors and their temperature derivatives

    International Nuclear Information System (INIS)

    Ganesan, S.; Gopalakrishnan, V.; Ramanadhan, M.M.; Cullen, D.E.

    1985-01-01

    The authors investigate the effect of interpolation error in the pre-processing codes LINEAR, RECENT and SIGMA1 on calculations of self-shielding factors and their temperature derivatives. They consider the 2.0347 to 3.3546 keV energy region for /sup 238/U capture, which is the NEACRP benchmark exercise on unresolved parameters. The calculated values of temperature derivatives of self-shielding factors are significantly affected by interpolation error. The sources of problems in both evaluated data and codes are identified and eliminated in the 1985 version of these codes. This paper helps to (1) inform code users to use only 1985 versions of LINEAR, RECENT, and SIGMA1 and (2) inform designers of other code systems where they may have problems and what to do to eliminate their problems

  13. Effects of chronic aluminum exposure on learning and memory and brain-derived nerve growth factor in rats

    Institute of Scientific and Technical Information of China (English)

    潘宝龙

    2013-01-01

    Objective To investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in SpragueDawley (SD) rats.Methods Thirty-two male SD rats were randomly and equally divided into 4 groups:control group and high-,middle-,and low-dose exposure groups.The rats in high-,middle-,and low-dose expo-

  14. Brain-derived neurotrophic factor Val66Met polymorphism and hippocampal activation during episodic encoding and retrieval tasks

    OpenAIRE

    Dennis, Nancy A.; Cabeza, Roberto; Need, Anna C.; Waters-Metenier, Sheena; Goldstein, David B.; LaBar, Kevin S.

    2010-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin which has been shown to regulate cell survival and proliferation, as well as synaptic growth and hippocampal long-term potentiation. A naturally occurring single nucleotide polymorphism in the human BDNF gene (val66met) has been associated with altered intercellular trafficking and regulated secretion of BDNF in met compared to val carriers. Additionally, previous studies have found a relationship between the BDNF val66met genotype an...

  15. Acute running stimulates hippocampal dopaminergic neurotransmission in rats, but has no influence on brain-derived neurotrophic factor

    OpenAIRE

    Goekint, Maaike; Bos, Inge; Heyman, Elsa; Meeusen, Romain; Michotte, Yvette; Sarre, Sophie

    2011-01-01

    Hippocampal brain-derived neurotrophic factor (BDNF) protein is increased with exercise in rats. Monoamines seem to play a role in the regulation of BDNF, and monoamine neurotransmission is known to increase with exercise. The purpose of this study was to examine the influence of acute exercise on monoaminergic neurotransmission and BDNF protein concentrations. Hippocampal microdialysis was performed in rats that were subjected to 60 min of treadmill running at 20 m/min or rest. Two hours pos...

  16. GC protein-derived macrophage-activating factor decreases ?-N-acetylgalactosaminidase levels in advanced cancer patients

    OpenAIRE

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-01-01

    ?-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort ...

  17. Analysis of spatiotemporal variability of C-factor derived from remote sensing data

    Science.gov (United States)

    Pechanec, Vilém; Mráz, Alexander; Benc, Antonín; Cudlín, Pavel

    2018-01-01

    Soil erosion is an important phenomenon that contributes to the degradation of agricultural land. Even though it is a natural process, human activities can significantly increase its impact on land degradation and present serious limitation on sustainable agricultural land use. Nowadays, the risk of soil erosion is assessed either qualitatively by expert assessment or quantitatively using model-based approach. One of the primary factors affecting the soil erosion assessment is a cover-management factor, C-factor. In the Czech Republic, several models are used to assess the C-factor on a long-term basis based on data collected using traditional tabular methods. This paper presents work to investigate the estimation of both long-term and short-term cover-management factors using remote sensing data. The results demonstrate a successful development of C-factor maps for each month of 2014, growing season average, and annual average for the Czech Republic. C-factor values calculated from remote sensing data confirmed expected trend in their temporal variability for selected crops. The results presented in this paper can be used for enhancing existing methods for estimating C-factor, planning future agricultural activities, and designing technical remediations and improvement activities of land use in the Czech Republic, which are also financially supported by the European Union funds.

  18. Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Tom J. Burdon

    2011-01-01

    Full Text Available During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

  19. Modelling crop land use change derived from influencing factors selected and ranked by farmers in North temperate agricultural regions.

    Science.gov (United States)

    Mehdi, Bano; Lehner, Bernhard; Ludwig, Ralf

    2018-08-01

    To develop meaningful land use scenarios, drivers that affect changes in the landscape are required. In this study, driving factors that influence farmers to change crops on their farm were determined. A questionnaire was administered to four independent groups of farmers who identified and ranked influencing factors pertaining to their choices of crops. The farmers were located in two mid-latitude agricultural watersheds (in Germany and Canada). The ranked influencing factors were used to develop a "farmer driven" scenario to 2040 in both watersheds. Results showed that the most important influencing factors for farmers to change crops were the "economic return of the crop" and "market factors". Yet, when the drivers of crop land use change were grouped into two categories of "financial" and "indirectly-related financial" factors, the "financial" factors made up approximately half of the influencing factors. For some responses, the "indirectly-related financial" factors (i.e. "access to farm equipment", the "farm experience", and "climate") ranked higher than or just as high as the financial factors. Overall, in the four farmer groups the differences between the rankings of the influencing factors were minor, indicating that drivers may be transferable between farms if the farmers are full-time and the farming regions have comparable growing seasons, access to markets, similar technology, and government programs for farm income. In addition to the "farmer driven" scenario, a "policy driven" scenario was derived for each watershed based only on available information on the financial incentives provided to farmers (i.e. agricultural subsidies, income support, crop insurance). The influencing factors ranked by the farmers provided in-depth information that was not captured by the "policy driven" scenario and contributed to improving predictions for crop land use development. This straight-forward method to rank qualitative data provided by farmers can easily be

  20. Statistically derived factors of varied importance to audiologists when making a hearing aid brand preference decision.

    Science.gov (United States)

    Johnson, Earl E; Mueller, H Gustav; Ricketts, Todd A

    2009-01-01

    To determine the amount of importance audiologists place on various items related to their selection of a preferred hearing aid brand manufacturer. Three hundred forty-three hearing aid-dispensing audiologists rated a total of 32 randomized items by survey methodology. Principle component analysis identified seven orthogonal statistical factors of importance. In rank order, these factors were Aptitude of the Brand, Image, Cost, Sales and Speed of Delivery, Exposure, Colleague Recommendations, and Contracts and Incentives. While it was hypothesized that differences among audiologists in the importance ratings of these factors would dictate their preference for a given brand, that was not our finding. Specifically, mean ratings for the six most important factors did not differ among audiologists preferring different brands. A statistically significant difference among audiologists preferring different brands was present, however, for one factor: Contracts and Incentives. Its assigned importance, though, was always lower than that for the other six factors. Although most audiologists have a preferred hearing aid brand, differences in the perceived importance of common factors attributed to brands do not largely determine preference for a particular brand.

  1. The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents

    DEFF Research Database (Denmark)

    Pedersen, Natascha Holbæk; Tarp, Jakob; Andersen, Lars Bo

    2017-01-01

    .034) and HOMA-IR (Std. β = 0.19, P = 0.004), and negatively associated with CRF (Std. β = -0.15, P = 0.026). In females, BDNF was positively associated with TG (Std. β = 0.14, P = 0.030) and negatively associated with waist circumference (WC) (Std. β = -0.16, P = 0.012). Conclusion: Serum BDNF was positively...... associated with a composite z-score of cardiovascular risk factors. This association seems to be mainly driven by the association between TG, HOMA-IR and serum BDNF, and particularly for males. Further longitudinal research is warranted to determine the temporal relationship between BDNF and cardiovascular...

  2. Analysis of spatio-temporal variability of C-factor derived from remote sensing data

    Science.gov (United States)

    Pechanec, Vilem; Benc, Antonin; Purkyt, Jan; Cudlin, Pavel

    2016-04-01

    In some risk areas water erosion as the present task has got the strong influence on agriculture and can threaten inhabitants. In our country combination of USLE and RUSLE models has been used for water erosion assessment (Krása et al., 2013). Role of vegetation cover is characterized by the help of vegetation protection factor, so-called C- factor. Value of C-factor is given by the ratio of washing-off on a plot with arable crops to standard plot which is kept as fallow regularly spud after any rain (Janeček et al., 2012). Under conditions we cannot identify crop structure and its turn, determination of C-factor can be problem in large areas. In such case we only determine C-factor according to the average crop representation. New technologies open possibilities for acceleration and specification of the approach. Present-day approach for the C-factor determination is based on the analysis of multispectral image data. Red and infrared spectrum is extracted and these parts of image are used for computation of vegetation index series (NDVI, TSAVI). Acquired values for fractional time sections (during vegetation period) are averaged out. At the same time values of vegetation indices for a forest and cleared area are determined. Also regressive coefficients are computed. Final calculation is done by the help of regressive equations expressing relation between values of NDVI and C-factor (De Jong, 1994; Van der Knijff, 1999; Karaburun, 2010). Up-to-date land use layer is used for the determination of erosion threatened areas on the base of selection of individual landscape segments of erosion susceptible categories of land use. By means of Landsat 7 data C-factor has been determined for the whole area of the Czech Republic in every month of the year of 2014. At the model area in a small watershed C-factor has been determined by the conventional (tabular) procedure. Analysis was focused on: i) variability assessment of C-factor values while using the conventional

  3. Human adipose-derived mesenchymal stromal cell pigment epithelium-derived factor cytotherapy modifies genetic and epigenetic profiles of prostate cancer cells.

    Science.gov (United States)

    Zolochevska, Olga; Shearer, Joseph; Ellis, Jayne; Fokina, Valentina; Shah, Forum; Gimble, Jeffrey M; Figueiredo, Marxa L

    2014-03-01

    Adipose-derived mesenchymal stromal cells (ASCs) are promising tools for delivery of cytotherapy against cancer. However, ASCs can exert profound effects on biological behavior of tumor cells. Our study aimed to examine the influence of ASCs on gene expression and epigenetic methylation profiles of prostate cancer cells as well as the impact of expressing a therapeutic gene on modifying the interaction between ASCs and prostate cancer cells. ASCs were modified by lentiviral transduction to express either green fluorescent protein as a control or pigment epithelium-derived factor (PEDF) as a therapeutic molecule. PC3 prostate cancer cells were cultured in the presence of ASC culture-conditioned media (CCM), and effects on PC3 or DU145. Ras cells were examined by means of real-time quantitative polymerase chain reaction, EpiTect methyl prostate cancer-focused real-time quantitative polymerase chain reaction arrays, and luciferase reporter assays. ASCs transduced with lentiviral vectors were able to mediate expression of several tumor-inhibitory genes, some of which correlated with epigenetic methylation changes on cocultured PC3 prostate cancer cells. When PC3 cells were cultured with ASC-PEDF CCM, we observed a shift in the balance of gene expression toward tumor inhibition, which suggests that PEDF reduces the potential tumor-promoting activity of unmodified ASCs. These results suggest that ASC-PEDF CCM can promote reprogramming of tumor cells in a paracrine manner. An improved understanding of genetic and epigenetic events in prostate cancer growth in response to PEDF paracrine therapy would enable a more effective use of ASC-PEDF, with the goal of achieving safer yet more potent anti-tumor effects. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  4. Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

    Science.gov (United States)

    Nishimura, R; Li, W; Kashishian, A; Mondino, A; Zhou, M; Cooper, J; Schlessinger, J

    1993-11-01

    Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth factors stimulate the phosphorylation of Nck and its association with autophosphorylated growth factor receptors. A panel of platelet-derived growth factor (PDGF) receptor mutations at tyrosine residues has been used to identify the Nck binding site. Here we show that mutation at Tyr-751 of the PDGF beta-receptor eliminates Nck binding both in vitro and in living cells. Moreover, the Y751F PDGF receptor mutant failed to mediate PDGF-stimulated phosphorylation of Nck in intact cells. A phosphorylated Tyr-751 is also required for binding of phosphatidylinositol-3 kinase to the PDGF receptor. Hence, the SH2 domains of p85 and Nck share a binding site in the PDGF receptor. Competition experiments with different phosphopeptides derived from the PDGF receptor suggest that binding of Nck and p85 is influenced by different residues around Tyr-751. Thus, a single tyrosine autophosphorylation site is able to link the PDGF receptor to two distinct SH2 domain-containing signaling molecules.

  5. Effects of vitamin D(3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis.

    Science.gov (United States)

    Kanda, Shigeru; Mochizuki, Yasushi; Miyata, Yasuyoshi; Kanetake, Hiroshi; Yamamoto, Nobuto

    2002-09-04

    The vitamin D(3)-binding protein (Gc protein)-derived macrophage activating factor (GcMAF) activates tumoricidal macrophages against a variety of cancers indiscriminately. We investigated whether GcMAF also acts as an antiangiogenic factor on endothelial cells. The effects of GcMAF on angiogenic growth factor-induced cell proliferation, chemotaxis, and tube formation were examined in vitro by using cultured endothelial cells (murine IBE cells, porcine PAE cells, and human umbilical vein endothelial cells [HUVECs]) and in vivo by using a mouse cornea micropocket assay. Blocking monoclonal antibodies to CD36, a receptor for the antiangiogenic factor thrombospondin-1, which is also a possible receptor for GcMAF, were used to investigate the mechanism of GcMAF action. GcMAF inhibited the endothelial cell proliferation, chemotaxis, and tube formation that were all stimulated by fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor-A, or angiopoietin 2. FGF-2-induced neovascularization in murine cornea was also inhibited by GcMAF. Monoclonal antibodies against murine and human CD36 receptor blocked the antiangiogenic action of GcMAF on the angiogenic factor stimulation of endothelial cell chemotaxis. In addition to its ability to activate tumoricidal macrophages, GcMAF has direct antiangiogenic effects on endothelial cells independent of tissue origin. The antiangiogenic effects of GcMAF may be mediated through the CD36 receptor.

  6. Lung-derived growth factors: possible paracrine effectors of fetal lung development

    International Nuclear Information System (INIS)

    Montes, A.M.

    1985-01-01

    A potential role for paracrine secretions in lung organogenesis has been hypothesized (Alescio and Piperno, 1957). These studies present direct support for the paracrine model by demonstrating the presence of locally produced mitogenic/maturational factors in fetal rat lung tissue. Conditioned serum free medium (CSFM) from nineteen-day fetal rat lung cultures was shown to contain several bioactive peptides as detected by 3 H-Thymidine incorporation into chick embryo and rat lung fibroblasts, as well as 14 C-choline incorporation into surfactant in mixed cell cultures. Using ion-exchange chromatography and Sephadex gel filtration, a partially purified mitogen, 11-III, was obtained. The partially purified 11-III stimulates mitosis in chick embryo fibroblasts and post-natal rat lung fibroblasts. Multiplication in fetal rat lung fibroblasts cultures is stimulated only when these are pre-incubated with a competence factor or unprocessed CSFM. This suggests the existence of an endogenously produced competence factor important in the regulation of fetal lung growth. Preparation 11-III does not possess surfactant stimulating activity as assessed by 3 H-choline incorporation into lipids in predominantly type-II cell cultures. These data demonstrate the presence of a maturational/mitogenic factor, influencing type-II mixed cell cultures. In addition, 11-III had been shown to play an autocrine role stimulating the proliferation of fetal lung fibroblasts. Finally, these data suggest the existence of a local produced competence factor

  7. Intracellular protein delivery activity of peptides derived from insulin-like growth factor binding proteins 3 and 5

    International Nuclear Information System (INIS)

    Goda, Natsuko; Tenno, Takeshi; Inomata, Kosuke; Shirakawa, Masahiro; Tanaka, Toshiki; Hiroaki, Hidekazu

    2008-01-01

    Insulin-like growth factor binding proteins (IGFBPs) have various IGF-independent cellular activities, including receptor-independent cellular uptake followed by transcriptional regulation, although mechanisms of cellular entry remain unclear. Herein, we focused on their receptor-independent cellular entry mechanism in terms of protein transduction domain (PTD) activity, which is an emerging technique useful for clinical applications. The peptides of 18 amino acid residues derived from IGFBP-3 and IGFBP-5, which involve heparin-binding regions, mediated cellular delivery of an exogenous protein into NIH3T3 and HeLa cells. Relative protein delivery activities of IGFBP-3/5-derived peptides were approximately 20-150% compared to that of the HIV-Tat peptide, a potent PTD. Heparin inhibited the uptake of the fusion proteins with IGFBP-3 and IGFBP-5, indicating that the delivery pathway is heparin-dependent endocytosis, similar to that of HIV-Tat. The delivery of GST fused to HIV-Tat was competed by either IGFBP-3 or IGFBP-5-derived synthetic peptides. Therefore, the entry pathways of the three PTDs are shared. Our data has shown a new approach for designing protein delivery systems using IGFBP-3/5 derived peptides based on the molecular mechanisms of IGF-independent activities of IGFBPs

  8. Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

    Science.gov (United States)

    Hafeman, Andrea E.; Li, Bing; Yoshii, Toshitaka; Zienkiewicz, Katarzyna; Davidson, Jeffrey M.; Guelcher, Scott A.

    2013-01-01

    Purpose The purpose of this work was to investigate the effects of triisocyanate composition on the biological and mechanical properties of biodegradable, injectable polyurethane scaffolds for bone and soft tissue engineering. Methods Scaffolds were synthesized using reactive liquid molding techniques, and were characterized in vivo in a rat subcutaneous model. Porosity, dynamic mechanical properties, degradation rate, and release of growth factors were also measured. Results Polyurethane scaffolds were elastomers with tunable damping properties and degradation rates, and they supported cellular infiltration and generation of new tissue. The scaffolds showed a two-stage release profile of platelet-derived growth factor, characterized by a 75% burst release within the first 24 h and slower release thereafter. Conclusions Biodegradable polyurethanes synthesized from triisocyanates exhibited tunable and superior mechanical properties compared to materials synthesized from lysine diisocyanates. Due to their injectability, biocompatibility, tunable degradation, and potential for release of growth factors, these materials are potentially promising therapies for tissue engineering. PMID:18516665

  9. Analysis of spatiotemporal variability of C-factor derived from remote sensing data

    Czech Academy of Sciences Publication Activity Database

    Pechanec, V.; Mráz, A.; Benc, A.; Cudlín, Pavel

    2018-01-01

    Roč. 12, č. 1 (2018), č. článku 016022. ISSN 1931-3195 R&D Projects: GA MŠk(CZ) LO1415 Grant - others:EHP,MF ČR(CZ) EHP-CZ02-OV-1-014-2014 Program:CZ02 Institutional support: RVO:86652079 Keywords : leaf-area index * soil-erosion * water erosion * ecosystem * model * vegetation * europe * fluxes * scale * ndvi * C-factor * soil erosion * erosion models * remote sensing * vegetation Subject RIV: EH - Ecology, Behaviour OBOR OECD: Environmental sciences (social aspects to be 5.7) Impact factor: 1.107, year: 2016

  10. Nitro-oleic acid regulates growth factor-induced differentiation of bone marrow-derived macrophages

    Czech Academy of Sciences Publication Activity Database

    Vereščáková, Hana; Ambrožová, Gabriela; Kubala, Lukáš; Perečko, Tomáš; Koudelka, Adolf; Vašíček, Ondřej; Rudolph, T.K.; Klinke, A.; Woodcock, S.R.; Freeman, B.A.; Pekarová, Michaela

    2017-01-01

    Roč. 104, MAR2017 (2017), s. 10-19 ISSN 0891-5849 R&D Projects: GA ČR GP13-40824P; GA ČR(CZ) GJ17-08066Y; GA MŠk(CZ) LD15069 Institutional support: RVO:68081707 Keywords : colony-stimulating factor * nitrated fatty-acids * hematopoietic stem-cells * gm-csf Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 5.606, year: 2016

  11. Student learning of upper-level thermal and statistical physics: The derivation and use of the Boltzmann factor

    Science.gov (United States)

    Thompson, John

    2015-04-01

    As the Physical Review Focused Collection demonstrates, recent frontiers in physics education research include systematic investigations at the upper division. As part of a collaborative project, we have examined student understanding of several topics in upper-division thermal and statistical physics. A fruitful context for research is the Boltzmann factor in statistical mechanics: the standard derivation involves several physically justified mathematical steps as well as the invocation of a Taylor series expansion. We have investigated student understanding of the physical significance of the Boltzmann factor as well as its utility in various circumstances, and identified various lines of student reasoning related to the use of the Boltzmann factor. Results from written data as well as teaching interviews suggest that many students do not use the Boltzmann factor when answering questions related to probability in applicable physical situations, even after lecture instruction. We designed an inquiry-based tutorial activity to guide students through a derivation of the Boltzmann factor and to encourage deep connections between the physical quantities involved and the mathematics. Observations of students working through the tutorial suggest that many students at this level can recognize and interpret Taylor series expansions, but they often lack fluency in creating and using Taylor series appropriately, despite previous exposure in both calculus and physics courses. Our findings also suggest that tutorial participation not only increases the prevalence of relevant invocation of the Boltzmann factor, but also helps students gain an appreciation of the physical implications and meaning of the mathematical formalism behind the formula. Supported in part by NSF Grants DUE-0817282, DUE-0837214, and DUE-1323426.

  12. Biomechanical force induces the growth factor production in human periodontal ligament-derived cells.

    Science.gov (United States)

    Ichioka, Hiroaki; Yamamoto, Toshiro; Yamamoto, Kenta; Honjo, Ken-Ichi; Adachi, Tetsuya; Oseko, Fumishige; Mazda, Osam; Kanamura, Narisato; Kita, Masakazu

    2016-01-01

    Although many reports have been published on the functional roles of periodontal ligament (PDL) cells, the mechanisms involved in the maintenance and homeostasis of PDL have not been determined. We investigated the effects of biomechanical force on growth factor production, phosphorylation of MAPKs, and intracellular transduction pathways for growth factor production in human periodontal ligament (hPDL) cells using MAPK inhibitors. hPDL cells were exposed to mechanical force (6 MPa) using a hydrostatic pressure apparatus. The levels of growth factor mRNA and protein were examined by real-time RT-PCR and ELISA. The phosphorylation of MAPKs was measured using BD™ CBA Flex Set. In addition, MAPKs inhibitors were used to identify specific signal transduction pathways. Application of biomechanical force (equivalent to occlusal force) increased the synthesis of VEGF-A, FGF-2, and NGF. The application of biomechanical force increased the expression levels of phosphorylated ERK and p38, but not of JNK. Furthermore, the levels of VEGF-A and NGF expression were suppressed by ERK or p38 inhibitor. The growth factors induced by biomechanical force may play a role in the mechanisms of homeostasis of PDL.

  13. Novel application of stem cell-derived factors for periodontal regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Inukai, Takeharu, E-mail: t-inukai@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Katagiri, Wataru, E-mail: w-kat@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Yoshimi, Ryoko, E-mail: lianzi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Osugi, Masashi, E-mail: masashi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Kawai, Takamasa, E-mail: takamasa@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Hibi, Hideharu, E-mail: hibihi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Ueda, Minoru, E-mail: mueda@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer Mesenchymal stem cells (MSCs) secrete a variety of cytokines. Black-Right-Pointing-Pointer Cytokines were detected in conditioned medium from cultured MSCs (MSC-CM). Black-Right-Pointing-Pointer MSC-CM enhanced activation of dog MSCs and periodontal ligament cells. Black-Right-Pointing-Pointer MSC-CM significantly promoted alveolar bone and cementum regeneration. Black-Right-Pointing-Pointer Multiple cytokines contained in MSC-CM promote periodontal regeneration. -- Abstract: The effect of conditioned medium from cultured mesenchymal stem cells (MSC-CM) on periodontal regeneration was evaluated. In vitro, MSC-CM stimulated migration and proliferation of dog MSCs (dMSCs) and dog periodontal ligament cells (dPDLCs). Cytokines such as insulin-like growth factor, vascular endothelial growth factor, transforming growth factor-{beta}1, and hepatocyte growth factor were detected in MSC-CM. In vivo, one-wall critical-size, intrabony periodontal defects were surgically created in the mandible of dogs. Dogs with these defects were divided into three groups that received MSC-CM, PBS, or no implants. Absorbable atelo-collagen sponges (TERUPLUG Registered-Sign ) were used as a scaffold material. Based on radiographic and histological observation 4 weeks after transplantation, the defect sites in the MSC-CM group displayed significantly greater alveolar bone and cementum regeneration than the other groups. These findings suggest that MSC-CM enhanced periodontal regeneration due to multiple cytokines contained in MSC-CM.

  14. Novel application of stem cell-derived factors for periodontal regeneration

    International Nuclear Information System (INIS)

    Inukai, Takeharu; Katagiri, Wataru; Yoshimi, Ryoko; Osugi, Masashi; Kawai, Takamasa; Hibi, Hideharu; Ueda, Minoru

    2013-01-01

    Highlights: ► Mesenchymal stem cells (MSCs) secrete a variety of cytokines. ► Cytokines were detected in conditioned medium from cultured MSCs (MSC-CM). ► MSC-CM enhanced activation of dog MSCs and periodontal ligament cells. ► MSC-CM significantly promoted alveolar bone and cementum regeneration. ► Multiple cytokines contained in MSC-CM promote periodontal regeneration. -- Abstract: The effect of conditioned medium from cultured mesenchymal stem cells (MSC-CM) on periodontal regeneration was evaluated. In vitro, MSC-CM stimulated migration and proliferation of dog MSCs (dMSCs) and dog periodontal ligament cells (dPDLCs). Cytokines such as insulin-like growth factor, vascular endothelial growth factor, transforming growth factor-β1, and hepatocyte growth factor were detected in MSC-CM. In vivo, one-wall critical-size, intrabony periodontal defects were surgically created in the mandible of dogs. Dogs with these defects were divided into three groups that received MSC-CM, PBS, or no implants. Absorbable atelo-collagen sponges (TERUPLUG®) were used as a scaffold material. Based on radiographic and histological observation 4 weeks after transplantation, the defect sites in the MSC-CM group displayed significantly greater alveolar bone and cementum regeneration than the other groups. These findings suggest that MSC-CM enhanced periodontal regeneration due to multiple cytokines contained in MSC-CM.

  15. Synthesis of trideuterated O-alkyl platelet activating factor and lyso derivatives

    International Nuclear Information System (INIS)

    Prakash, C.; Saleh, S.; Taber, D.F.; Blair, I.A.

    1989-01-01

    Racemic heavy isotope analogs of 1-O-alkyl-sn-glycero-3-phosphocholine (lysoPAF) and 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (PAF) were prepared for use as internal standards to facilitate quantitative studies based on mass spectrometry. Starting from pentadecane-1,15-diol and rac-glycerol-1,2-acetonide, a convergent synthesis of 1-O-[16'-2H3]hexadecyl and 1-O-[18'-2H3]octadecyl rac-glycero-3-phosphocholine and their acetyl derivatives is described. Three deuterium atoms were introduced at the terminal position of the 1-O-alkyl group by displacement of the p-toluensulfonyl group from 1-O-alkyl-15'-p-toluensulfonate and 1-O-alkyl-17'-p-toluensulfonate with [2H3]-methylmagnesium iodide. The 1-O-alkyl-17'-p-toluensulfonate was obtained by reaction of the 1-O-alkyl-15'-p-toluensulfonate with allylmagnesium bromide, followed by reductive ozonolysis and treatment with p-toluene-sulfonyl chloride. The hydroxyl group at C-2 was protected by a benzyl group and removed at a late stage in the synthesis. This provided the corresponding lyso-derivatives or allowed preparation of racemic PAF by subsequent acetylation of the free hydroxy group. The phosphocholine moiety was introduced at glycerol C-3 by reaction with bromoethyldichlorophosphate and trimethylamine. The synthetic compounds were analyzed by FAB/MS and GC/NICIMS. They were shown to contain less than 0.6% protium impurity

  16. Human Breast Adipose-Derived Stem Cells Transfected with the Stromal Cell-Derived Factor-1 Receptor CXCR4 Exhibit Enhanced Viability in Human Autologous Free Fat Grafts

    Directory of Open Access Journals (Sweden)

    Fang-tian Xu

    2014-11-01

    Full Text Available Background: The main complication of autologous free fat tissue transplantation is fat resorption and calcification due to the ischemic necrosis of fat. The promotion of transplant neovascularization soon after autologous free fat grafts may reduce these outcomes. In adulthood, stromal cell-derived factor-1 (SDF-1 and its membrane receptor C-X-C chemokine receptor type 4 (CXCR4 are involved in the homing and migration of multiple stem cell types, neovascularization, and cell proliferation. We hypothesized that CXCR4 may improve the long-term survival of free fat tissue transplants by recruiting endothelial progenitor cells (EPCs and may therefore improve graft revascularization. In this study, we aimed to determine the effect of human breast adipose-derived stem cells (HBASCs transfected with the CXCR4 gene on the survival rate of human autologous free fat transplants in nude mice. Methods: Human breast adipose-derived stem cells (HBASCs were expanded ex vivo for 3 passages, labeled with green fluorescent protein (GFP and transfected with CXCR4 or left untransfected. Autologous fat tissues were mixed with the GFP-labeled, CXCR4-transfected HBASCs (group A, GFP-labeled HBASCs (group B, the known vascularization-promoting agent VEGF (group C, or medium (group D and then injected subcutaneously into 32 nude mice at 4 spots in a random fashion. Six months later, the transplanted tissue volume and histology were evaluated, and neo-vascularization was quantified by counting the capillaries. CXCR4 and SDF-1α mRNA expression in the transplants was determined using real-time quantitative PCR analysis (qPCR. Results: The data revealed that the control (group D transplant volume survival was 28.3 ± 4.5%. Mixing CXCR4-transfected (group A and untransfected (group B HBASCs significantly increased transplant volume survival (79.5 ± 8.3% and 67.2 ± 5.9%, respectively, whereas VEGF-transfected HBASCs (group C were less effective (41.2 ± 5.1%. Histological

  17. [Analysis of factors related to the number of mesenchymal stem cells derived from synovial fluid of the temporomandibular joint].

    Science.gov (United States)

    Sun, Y P; Zheng, Y H; Zhang, Z G

    2017-06-09

    Objective: To analyze related factors on the number of mesenchymal stem cells in the synovial fluid of the temporomandibular joint (TMJ) and provide an research basis for understanding of the source and biological role of mesenchymal stem cells derived from synovial fluid in TMJ. Methods: One hundred and twenty-two synovial fluid samples from 91 temporomandibular disorders (TMD) patients who visited in Department of TMJ Center, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University from March 2013 to December 2013 were collected in this study, and 6 TMJ synovial fluid samples from 6 normal volunteers who were studying in the North Campus of Sun Yat-sen University were also collected, so did their clinical information. Then the relation between the number of mesenchymal stem cells derived from synovial fluid and the health status of the joints, age of donor, disc perforation, condylar bony destruction, blood containing and visual analogue scale score of pain were investigated using Mann-Whitney U test and Spearman rank correlation test. Results: The number of mesenchymal stem cells derived from synovial fluid had no significant relation with visual analogue scale score of pain ( r= 0.041, P= 0.672), blood containing ( P= 0.063), condylar bony destruction ( P= 0.371). Linear correlation between the number of mesenchymal stem cells derived from synovial fluid and age of donor was very week ( r= 0.186, P= 0.043). The number of mesenchymal stem cells up-regulated when the joint was in a disease state ( P= 0.001). The disc perforation group had more mesenchymal stem cells in synovial fluid than without disc perforation group ( P= 0.042). Conclusions: The number of mesenchymal stem cells derived from synovial fluid in TMJ has no correlation with peripheral blood circulation and condylar bony destruction, while has close relation with soft tissue structure damage of the joint.

  18. Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis.

    Science.gov (United States)

    Takagi, Satoshi; Takemoto, Ai; Takami, Miho; Oh-Hara, Tomoko; Fujita, Naoya

    2014-08-01

    The interactions of tumor cells with platelets contribute to the progression of tumor malignancy, and the expression levels of platelet aggregation-inducing factors positively correlate with the metastatic potential of osteosarcoma cells. However, it is unclear how tumor-platelet interaction contributes to the proliferation of osteosarcomas. We report here that osteosarcoma-platelet interactions induce the release of platelet-derived growth factor (PDGF) from platelets, which promotes the proliferation of osteosarcomas. Co-culture of platelets with MG63 or HOS osteosarcoma cells, which could induce platelet aggregation, enhanced the proliferation of each cell line in vitro. Analysis of phospho-antibody arrays revealed that co-culture of MG63 cells with platelets induced the phosphorylation of platelet derived growth factor receptor (PDGFR) and Akt. The addition of supernatants of osteosarcoma-platelet reactants also increased the growth of MG63 and HOS cells as well as the level of phosphorylated-PDGFR and -Akt. Sunitinib or LY294002, but not erlotinib, significantly inhibited the platelet-induced proliferation of osteosarcoma cells, indicating that PDGF released from platelets plays an important role in the proliferation of osteosarcomas by activating the PDGFR and then Akt. Our results suggest that inhibitors that specifically target osteosarcoma-platelet interactions may eradicate osteosarcomas. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  19. Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

    Science.gov (United States)

    Ishii, Makoto; Iadecola, Costantino

    2016-05-01

    Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells

    Directory of Open Access Journals (Sweden)

    Fat-Moon Suk

    2013-01-01

    Full Text Available Activating transcription factor-(ATF- 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. NBM-TP-007-GS-002 (GS-002 is a Taiwanese propolin G (PPG derivative. In this study, we examined the antitumor effects of GS-002 in human hepatoma Hep3B and HepG2 cells in vitro. First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners. Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose polymerase (PARP. GS-002 also induced endoplasmic reticular (ER stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78, growth arrest- and DNA damage-inducible gene 153 (GADD153, phosphorylated eukaryotic initiation factor 2α (eIF2α, phosphorylated protein endoplasmic-reticular-resident kinase (PERK, and ATF-3. The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK signaling pathways in GS-002-treated cells. Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells. These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug.

  1. Synthetic NCAM-derived Ligands of the Fibroblast Growth Factor Receptor

    DEFF Research Database (Denmark)

    Hansen, Stine; Li, Shizhong; Bock, Elisabeth

    2008-01-01

    The neural cell adhesion molecule (NCAM) responds to cues in the external environment and transmits signals to the cell through extracellular and intracellular interactions with a number of other signal transduction molecules. One such NCAM interaction partner is the fibroblast growth factor...... various FN3 module loop regions, have been identified as FGFR ligands. All four peptides activate FGFR and differentially modulate a number of neuronal functions, such as differentiation, survival, and synaptic changes that are important for learning, memory, and neuronal regeneration....

  2. Continuous Release of Tumor-Derived Factors Improves the Modeling of Cachexia in Muscle Cell Culture

    Directory of Open Access Journals (Sweden)

    Robert W. Jackman

    2017-09-01

    Full Text Available Cachexia is strongly associated with a poor prognosis in cancer patients but the biological trigger is unknown and therefore no therapeutics exist. The loss of skeletal muscle is the most deleterious aspect of cachexia and it appears to depend on secretions from tumor cells. Models for studying wasting in cell culture consist of experiments where skeletal muscle cells are incubated with medium conditioned by tumor cells. This has led to candidates for cachectic factors but some of the features of cachexia in vivo are not yet well-modeled in cell culture experiments. Mouse myotube atrophy measured by myotube diameter in response to medium conditioned by mouse colon carcinoma cells (C26 is consistently less than what is seen in muscles of mice bearing C26 tumors with moderate to severe cachexia. One possible reason for this discrepancy is that in vivo the C26 tumor and skeletal muscle share a circulatory system exposing the muscle to tumor factors in a constant and increasing way. We have applied Transwell®-adapted cell culture conditions to more closely simulate conditions found in vivo where muscle is exposed to the ongoing kinetics of constant tumor secretion of active factors. C26 cells were incubated on a microporous membrane (a Transwell® insert that constitutes the upper compartment of wells containing plated myotubes. In this model, myotubes are exposed to a constant supply of cancer cell secretions in the medium but without direct contact with the cancer cells, analogous to a shared circulation of muscle and cancer cells in tumor-bearing animals. The results for myotube diameter support the idea that the use of Transwell® inserts serves as a more physiological model of the muscle wasting associated with cancer cachexia than the bolus addition of cancer cell conditioned medium. The Transwell® model supports the notion that the dose and kinetics of cachectic factor delivery to muscle play a significant role in the extent of pathology.

  3. Adhesion of nitrile rubber to UV-assisted surface chemical modified PET fabric, part II: Interfacial characterization of MDI grafted PET

    Energy Technology Data Exchange (ETDEWEB)

    Razavizadeh, Mahmoud; Jamshidi, Masoud, E-mail: mjamshidi@iust.ac.ir

    2016-08-30

    Highlights: • In this research UV-irradiated PET fabric was chemically modified. • The fabric at first carboxylated under UV irradiation using glutaric anhydride, then it was grafted using isocyanate (i.e. MDI). • The surface of the fabric was characterized before and after each treating satge. • The composite samples were prepared and tested for T-Peel test. The surfaces of the fabrics were surface characterized to understand. - Abstract: Fiber to rubber adhesion is an important subject in rubber industry. It is well known that surface treatment (i.e. physical, mechanical and chemical) is an effective method to improve interfacial bonding of fibers and/or fabrics to rubbers. UV irradiation is an effective method which has been used to increase fabric-rubber interfacial interactions. In this research UV assisted chemical modification of PET fabrics was used to increase PET to nitrile rubber (NBR) adhesion. Nitrile rubber is a perfect selection as fuel and oil resistant rubber. However it has weak bonding to PET fabric. For this purpose PET fabric was carboxylated under UV irradiation and then methylenediphenyl diisocyanate (MDI) was grafted on carboxylated PET. The chemical composition of the fabric before and after surface treatment was investigated by X-ray photoelectron spectroscopy (XPS). The sectional morphology of the experimental PET fibers and the interface between rubber compound and PET fabric was studied using scanning electron microscope (SEM). The morphology and structure of the product were analyzed by an energy dispersive X-ray spectrometer (EDX). FTIR-ATR and H NMR analysis were used to assess surface modifications on the PET irradiated fabrics.

  4. Adhesion of nitrile rubber to UV-assisted surface chemical modified PET fabric, part II: Interfacial characterization of MDI grafted PET

    International Nuclear Information System (INIS)

    Razavizadeh, Mahmoud; Jamshidi, Masoud

    2016-01-01

    Highlights: • In this research UV-irradiated PET fabric was chemically modified. • The fabric at first carboxylated under UV irradiation using glutaric anhydride, then it was grafted using isocyanate (i.e. MDI). • The surface of the fabric was characterized before and after each treating satge. • The composite samples were prepared and tested for T-Peel test. The surfaces of the fabrics were surface characterized to understand. - Abstract: Fiber to rubber adhesion is an important subject in rubber industry. It is well known that surface treatment (i.e. physical, mechanical and chemical) is an effective method to improve interfacial bonding of fibers and/or fabrics to rubbers. UV irradiation is an effective method which has been used to increase fabric-rubber interfacial interactions. In this research UV assisted chemical modification of PET fabrics was used to increase PET to nitrile rubber (NBR) adhesion. Nitrile rubber is a perfect selection as fuel and oil resistant rubber. However it has weak bonding to PET fabric. For this purpose PET fabric was carboxylated under UV irradiation and then methylenediphenyl diisocyanate (MDI) was grafted on carboxylated PET. The chemical composition of the fabric before and after surface treatment was investigated by X-ray photoelectron spectroscopy (XPS). The sectional morphology of the experimental PET fibers and the interface between rubber compound and PET fabric was studied using scanning electron microscope (SEM). The morphology and structure of the product were analyzed by an energy dispersive X-ray spectrometer (EDX). FTIR-ATR and H NMR analysis were used to assess surface modifications on the PET irradiated fabrics.

  5. The in Vitro Assessment of Biochemical Factors in Hepatocyte like Cells Derived from Umbilical Cord Blood Stem Cells

    Directory of Open Access Journals (Sweden)

    A KHoramroodi

    2009-10-01

    Full Text Available Introduction & Objective: Umbilical cord blood (UCB is a source of Hematopoietic Stem Cells (HSC and progenitor cells that can reconstitute the hematopoietic system in patients with malignant and nonmalignant disorders. Mesenchymal stem cell-derived from umbilical cord blood (UCB have been differentiated to some kind of cells, such as osteobblast, adipoblast and chondroblast in Vitro. This study examined the differentiation of Umbilical Cord Blood (UCB derived stem cells to functional hepatocytes. Materials & Methods: The present study was an experimental study which was carried out in the Payam-e-Noor University of Tehran in cooperation with Hamedan University of Medical Sciences in 2008. Umbilical cord blood (UCB was obtained from Fatemieh hospital (Hamadan, Iran. Stem cells were isolated from the cord blood by combining density gradient centrifugation with plastic adherence. When the isolated cells reached 80% confluence, they differentiated to hepatocyte like cells. The medium which was used was consists of DMEM and 10% Fetal Bovine Serum (FBS supplemented with 20 ng/mL Hepatocyte Growth Factor (HGF, 10 ng/mL basic Fibroblast Growth Factor (bFGF and 20 ng/mL Oncostatin M (OSM.The medium was changed every 3 days and stored for Albumin (ALB, Alpha Fetoprotein (AFP, Alkaline Phosphatase (ALP, and urea assay. Finally PAS stain was done to study Glycogen storage in the differentiated cell. Results: Measurement of biochemical factors in different days showed that concentration of albumin (ALB, alpha fetoprotein (AFP, alkaline phosphatase (ALP, and Urea gradually increased. Also, PAS staining showed the storage of glycogen in these cells. Conclusion: Stem cell-derived from human umbilical cord blood (HUCB is a new source of cell types for cell transplantation therapy of hepatic diseases and under certain conditions these cells can differentiate into liver cells.

  6. ROLE OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF IN THE DIAGNOSIS OF COGNTIVE DYSFUNCTION IN PATIENTS WITH TYPE 2 DIABETES

    Directory of Open Access Journals (Sweden)

    Irina Vladimirovna Gatskikh

    2016-02-01

    Full Text Available One of the heavy progressive vascular complications of type 2 diabetes is a central nervous system, manifesting cognitive dysfunction due to metabolic changes. Goal. Defining the role of brain-derived neurotrophic factor (BDNF in the diagnosis of cognitive dysfunction in patients with type 2 diabetes. Materials and methods. The study involved 83 patients with type 2 diabetes at the age of 40 - 70 years. Complex examination included clinical and laboratory examination, neuropsychological testing. To screen for cognitive impairment used the Montreal Cognitive Assessment Scale (MOS test. To identify early markers of cognitive impairment was determined the level of brain-derived neurotrophic factor (BDNF. Results. The study found a negative correlation between the level of BDNF and the HbA1c (r = - 0,494, p = 0.01, fasting glucose (r = - 0,499, p = 0.01, and a positive relationship between the level of BDNF and cognitive function in patients with type 2 diabetes. Conclusion. In patients with type 2 diabetes revealed cognitive dysfunction in the form of reduced memory, attention, optical-dimensional activity that correlated with chronic hyperglycemia. The role of brain-derived neurotrophic factor (BDNF in the complex diagnosis of cognitive dysfunction in patients with type 2 diabetes. With an increase in HbA1c in patients with type 2 diabetes reduces the level of BDNF in the blood plasma, and a decline in cognitive function. Recommended use of BDNF as an additional marker of cognitive dysfunction in patients with type 2 diabetes.

  7. Effects of Fluid Ingestion on Brain-Derived Neurotrophic Factor and Cognition During Exercise in the Heat

    Directory of Open Access Journals (Sweden)

    Roh Hee-Tae

    2017-08-01

    Full Text Available We investigated the effects of fluid ingestion during exercise in different environments on the serum brain-derived neurotrophic factor and cognition among athletes. Ten collegiate male athletes (soccer, n = 5; rugby, n = 5 were enrolled, and they completed running tests in the following four conditions (60 min each: 1 thermoneutral temperature at 18°C (group 18; 2 high ambient temperature at 32°C without fluid ingestion (group 32; 3 high ambient temperature at 32°C with water ingestion (group 32+W; and 4 high ambient temperature at 32°C with sports drink ingestion (group 32+S. Serum brain-derived neurotrophic factor levels significantly increased in group 18 immediately after exercise when compared with those at rest and were significantly higher than those in group 32 immediately and 60 min after exercise (p < 0.05. In the Stroop Color and Word Test, significantly increased Word, Color, and Color-Word scores were observed in group 18 immediately after exercise compared to those at rest (p < 0.05. However, the Color-Word score appeared to be significantly lower in group 32 immediately after exercise compared to the other groups (p < 0.05 and at 60 min post-exercise compared to group 18 (p < 0.05. We found that the exercise performed in a thermoneutral environment improved cognitive function, but the exercise performed in a hot environment did not. The differences according to the exercise environment would be largely affected by brain-derived neurotrophic factor, and fluid ingestion regardless of the type of drink (water or sports beverage was assumed to have contributed to the improvement in cognitive function caused by exercising in a hot environment.

  8. The Effects of Environmental Factors on Smooth Muscle Cells Differentiation from Adipose-Derived Stem Cells and Esophagus Tissues Engineering

    DEFF Research Database (Denmark)

    Wang, Fang

    Adipose-derived stem cells (ASCs) are increasingly being used for regenerative medicine and tissue engineering. Smooth muscle cells (SMCs) can be differentiated from ASCs. Oxygen is a key factor influencing the stem cell differentiation. Tissue engineered esophagus has been a preferred solution...... of esophagus was studied. Our results showed that both SMCs and ASCs could attach on the porcine esophageal acellular matrix (EAM) scaffold in vitro after 24 hours and survive until 7 days. Thus ASCs might be a substitute for SMCs in the construction of tissue engineered esophageal muscle layer....

  9. ZBED6, a novel transcription factor derived from a domesticated DNA transposon regulates IGF2 expression and muscle growth

    DEFF Research Database (Denmark)

    Markljung, Ellen; Jiang, Lin; Jaffe, Jacob D

    2009-01-01

    and find that the protein, named ZBED6, is previously unknown, specific for placental mammals, and derived from an exapted DNA transposon. Silencing of Zbed6 in mouse C2C12 myoblasts affected Igf2 expression, cell proliferation, wound healing, and myotube formation. Chromatin immunoprecipitation (Ch......, including development and transcriptional regulation. The phenotypic effects in mutant pigs and ZBED6-silenced C2C12 myoblasts, the extreme sequence conservation, its nucleolar localization, the broad tissue distribution, and the many target genes with essential biological functions suggest that ZBED6...... is an important transcription factor in placental mammals, affecting development, cell proliferation, and growth....

  10. Brain-derived neurotrophic factor exerts neuroprotective actions against amyloid β-induced apoptosis in neuroblastoma cells

    OpenAIRE

    KIM, JIN HEE

    2014-01-01

    Alzheimer’s disease (AD) brains demonstrate decreased levels of brain-derived neurotrophic factor (BDNF) and increased levels of β-amyloid peptide (Aβ), which is neurotoxic. The present study assessed the impact of BDNF on the toxic effects of Aβ25–35-induced apoptosis and the effects on BDNF-mediated signaling using the MTT assay, western blotting and reverse transcription quantitative polymerase chain reaction. Aβ25–35 was found to induce an apoptosis, dose-dependent effect on SH-SY5Y neuro...

  11. Factors influencing publication of scientific articles derived from masters theses in public health.

    Science.gov (United States)

    Hollmann, Malen; Borrell, Carme; Garin, Olatz; Fernández, Esteve; Alonso, Jordi

    2015-05-01

    To evaluate theses of a Masters program in Public Health (MPH), in terms of the students' and theses' characteristics that influence publication of the thesis as a scientific article. Longitudinal study of students who successfully completed the MPH at Universitat Pompeu Fabra and Universitat Autònoma de Barcelona (Spain) from 2006 to 2010. Participants completed an electronic survey and additional data were gathered from university files. 162 students participated in the study (83 % response rate). 60.5 % had already published an article derived from their thesis at the time of the study or were in process of publishing it. The likelihood of publishing in a peer-reviewed journal was greater among women (aRR = 1.41), among those who had a bachelor's degree in sciences other than health (aRR = 1.40), had completed the MPH on time (aRR = 2.10), had enrolled in a doctoral program after the MPH (aRR = 1.44) or had a masters thesis score of ≥7 (aRR = 1.61). The majority of MPH students published their thesis in a peer-reviewed journal. The strongest predictors of successful publication were related to academic performance.

  12. Comparison of plasma pigment epithelium-derived factor (PEDF), retinol binding protein 4 (RBP-4), chitinase-3-like protein 1 (YKL-40) and brain-derived neurotrophic factor (BDNF) for the identification of insulin resistance.

    Science.gov (United States)

    Toloza, F J K; Pérez-Matos, M C; Ricardo-Silgado, M L; Morales-Álvarez, M C; Mantilla-Rivas, J O; Pinzón-Cortés, J A; Pérez-Mayorga, M; Arévalo-García, M L; Tolosa-González, G; Mendivil, C O

    2017-09-01

    To evaluate and compare the association of four potential insulin resistance (IR) biomarkers (pigment-epithelium-derived factor [PEDF], retinol-binding-protein-4 [RBP-4], chitinase-3-like protein 1 [YKL-40] and brain-derived neurotrophic factor [BDNF]) with objective measures of IR. We studied 81 subjects with different metabolic profiles. All participants underwent a 5-point OGTT with calculation of multiple IR indexes. A subgroup of 21 participants additionally underwent a hyperinsulinemic-euglycemic clamp. IR was defined as belonging to the highest quartile of incremental area under the insulin curve (iAUCins), or to the lowest quartile of the insulin sensitivity index (ISI). PEDF was associated with adiposity variables. PEDF and RBP4 increased linearly across quartiles of iAUCins (for PEDF p-trend=0.029; for RBP-4 p-trend=0.053). YKL-40 and BDNF were not associated with any adiposity or IR variable. PEDF and RBP-4 levels identified individuals with IR by the iAUCins definition: A PEDF cutoff of 11.9ng/mL had 60% sensitivity and 68% specificity, while a RBP-4 cutoff of 71.6ng/mL had 70% sensitivity and 57% specificity. In multiple regression analyses simultaneously including clinical variables and the studied biomarkers, only BMI, PEDF and RBP-4 remained significant predictors of IR. Plasma PEDF and RBP4 identified IR in subjects with no prior diagnosis of diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Immunohistochemical examination of effects of kefir, koumiss and commercial probiotic capsules on platelet derived growth factor-c and platelet derived growth factor receptor-alpha expression in mouse liver and kidney.

    Science.gov (United States)

    Bakir, B; Sari, E K; Aydin, B D; Yildiz, S E

    2015-04-01

    We investigated using immunohistochemistry the effects of kefir, koumiss and commercial probiotic capsules on the expression of platelet derived growth factor-c (PDGF-C) and platelet derived growth factor receptor-alpha (PDGFR-α) in mouse liver and kidney. Mice were assigned to four groups: group 1 was given commercial probiotic capsules, group 2 was given kefir, group 3 was given koumiss and group 4 was untreated. After oral administration for 15 days, body weights were recorded and liver and kidney tissue samples were obtained. Hematoxylin and eosin staining was used to examine histology. PDGF-C and PDGFR-α in liver and kidney were localized using the streptavidin-biotin peroxidase complex method (ABC). We found that the weights of the mice in the kefir, koumiss and commercial probiotic capsules groups increased compared to the control group. No differences in liver and kidney histology were observed in any of the experimental groups. Kefir, koumiss and the commercial probiotic preparation increased PDGF-C and PDGFR-α expression.

  14. The Effects of Imatinib Mesylate on Cellular Viability, Platelet Derived Growth Factor and Stem Cell Factor in Mouse Testicular Normal Leydig Cells.

    Science.gov (United States)

    Kheradmand, Fatemeh; Hashemnia, Seyyed Mohammad Reza; Valizadeh, Nasim; Roshan-Milani, Shiva

    2016-01-01

    Growth factors play an essential role in the development of tumor and normal cells like testicular leydig cells. Treatment of cancer with anti-cancer agents like imatinib mesylate may interfere with normal leydig cell activity, growth and fertility through failure in growth factors' production or their signaling pathways. The purpose of the study was to determine cellular viability and the levels of, platelet derived growth factor (PDGF) and stem cell factor (SCF) in normal mouse leydig cells exposed to imatinib, and addressing the effect of imatinib on fertility potential. The mouse TM3 leydig cells were treated with 0 (control), 2.5, 5, 10 and 20 μM imatinib for 2, 4 and 6 days. Each experiment was repeated three times (15 experiments in each day).The cellular viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, one-way ANOVA with Tukey's post hoc and Kruskal-Wallis test were performed. A p-value less than 0.05 was considered statistically significant. With increasing drug concentration, cellular viability decreased significantly (pcellular viability, PDGF and SCF levels. Imatinib may reduce fertility potential especially at higher concentrations in patients treated with this drug by decreasing cellular viability. The effect of imatinib on leydig cells is associated with PDGF stimulation. Of course future studies can be helpful in exploring the long term effects of this drug.

  15. Regulation of Brain-Derived Neurotrophic Factor and Growth Factor Signaling Pathways by Tyrosine Phosphatase Shp2 in the Retina: A Brief Review

    Directory of Open Access Journals (Sweden)

    Mojdeh Abbasi

    2018-03-01

    Full Text Available SH2 domain-containing tyrosine phosphatase-2 (PTPN11 or Shp2 is a ubiquitously expressed protein that plays a key regulatory role in cell proliferation, differentiation and growth factor (GF signaling. This enzyme is well expressed in various retinal neurons and has emerged as an important player in regulating survival signaling networks in the neuronal tissues. The non-receptor phosphatase can translocate to lipid rafts in the membrane and has been implicated to regulate several signaling modules including PI3K/Akt, JAK-STAT and Mitogen Activated Protein Kinase (MAPK pathways in a wide range of biochemical processes in healthy and diseased states. This review focuses on the roles of Shp2 phosphatase in regulating brain-derived neurotrophic factor (BDNF neurotrophin signaling pathways and discusses its cross-talk with various GF and downstream signaling pathways in the retina.

  16. Effect of Mirtazapine Treatment on Serum Levels of Brain-Derived Neurotrophic Factor and Tumor Necrosis Factor-α in Patients of Major Depressive Disorder with Severe Depression.

    Science.gov (United States)

    Gupta, Rachna; Gupta, Keshav; Tripathi, A K; Bhatia, M S; Gupta, Lalit K

    2016-01-01

    This study evaluated the clinical efficacy of mirtazapine and its effect on serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) levels in patients of major-depressive disorder (MDD) with severe depression. Patients (aged 18-60) with MDD diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥25 were included (n = 30). Mirtazapine was given in the doses of 30 mg/day. All patients were followed up for 12 weeks for the evaluation of clinical efficacy, safety along with serum BDNF and TNF-α levels. HAM-D score at the start of treatment was 30.1 ± 1.92, which significantly (p depressed patients and treatment response is associated with an increase in serum BDNF and a decrease in serum TNF-α levels. © 2016 S. Karger AG, Basel.

  17. Nutrient-derived dietary patterns and risk of colorectal cancer: a factor analysis in Uruguay.

    Science.gov (United States)

    De Stefani, Eduardo; Ronco, Alvaro L; Boffetta, Paolo; Deneo-Pellegrini, Hugo; Correa, Pelayo; Acosta, Gisele; Mendilaharsu, Maria

    2012-01-01

    In order to explore the role of nutrients and bioactive related substances in colorectal cancer, we conducted a case-control in Uruguay, which is the country with the highest production of beef in the world. Six hundred and eleven (611) cases afflicted with colorectal cancer and 1,362 controls drawn from the same hospitals in the same time period were analyzed through unconditional multiple logistic regression. This base population was submitted to a principal components factor analysis and three factors were retained. They were labeled as the meat-based, plant-based, and carbohydrates patterns. They were rotated using orthogonal varimax method. The highest risk was positively associated with the meat-based pattern (OR for the highest quartile versus the lowest one 1.63, 95 % CI 1.22-2.18, P value for trend = 0.001), whereas the plant-based pattern was strongly protective (OR 0.60, 95 % CI 0.45-0.81, P value for trend pattern was only positively associated with colon cancer risk (OR 1.46, 95 % CI 1.02-2.09). The meat-based pattern was rich in saturated fat, animal protein, cholesterol, and phosphorus, nutrients originated in red meat. Since herocyclic amines are formed in the well-done red meat through the action of amino acids and creatine, it is suggestive that this pattern could be an important etiologic agent for colorectal cancer.

  18. Factors related to accelerometer-derived physical activity in Pacific children aged 6 years.

    Science.gov (United States)

    Oliver, Melody; Schluter, Philip J; Schofield, Grant M; Paterson, Janis

    2011-01-01

    The objective of this study was to investigate potential factors related to Pacific children's moderate-to-vigorous physical activity (MVPA). A total of 393 Pacific children aged 6 years and their mothers were invited to participate. Participants wore accelerometers over 8 days; height, weight, and waist circumference were measured, and mothers reported on individual, social, and perceived environmental factors. Generalized estimation equation models were used to identify associates of children's daily MVPA. In all, 135 children and 91 mothers were included in analyses. Children spent 24% of time in MVPA; 99% of days had ≥60 minutes of MVPA. Higher maternal MVPA, male sex, longer sunlight hours, and rain-free days were associated with children's MVPA. Approaches for improving activity in Pacific children may be most efficacious if strategies for inclement weather and the encouragement of activity in mothers and, in particular, their daughters are included. Also, 60 minutes of daily MVPA may be insufficient to protect Pacific children from increased body size.

  19. Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Bin [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Li, Wei [Department of Gerontology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qichang [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Qin, Tao [Department of Hepatobiliary Pancreatic Surgery, People' s Hospital of Zhengzhou University, School of Medicine, Zhengzhou University, Zhengzhou 450003 (China); Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Liu, Sanguang, E-mail: sanguang1998@sina.com [Department of Hepatobiliary Surgery, The Second Hospital, Hebei Medical University, Shijiazhuang 050000 (China); Song, Zifang, E-mail: zsong@hust.edu.cn [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China)

    2015-07-17

    Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation.

  20. Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Yang, Bin; Li, Wei; Zheng, Qichang; Qin, Tao; Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen; Liu, Sanguang; Song, Zifang

    2015-01-01

    Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation

  1. From Molecular to Nanotechnology Strategies for Delivery of Neurotrophins: Emphasis on Brain-Derived Neurotrophic Factor (BDNF)

    Science.gov (United States)

    Géral, Claire; Angelova, Angelina; Lesieur, Sylviane

    2013-01-01

    Neurodegenerative diseases represent a major public health problem, but beneficial clinical treatment with neurotrophic factors has not been established yet. The therapeutic use of neurotrophins has been restrained by their instability and rapid degradation in biological medium. A variety of strategies has been proposed for the administration of these leading therapeutic candidates, which are essential for the development, survival and function of human neurons. In this review, we describe the existing approaches for delivery of brain-derived neurotrophic factor (BDNF), which is the most abundant neurotrophin in the mammalian central nervous system (CNS). Biomimetic peptides of BDNF have emerged as a promising therapy against neurodegenerative disorders. Polymer-based carriers have provided sustained neurotrophin delivery, whereas lipid-based particles have contributed also to potentiation of the BDNF action. Nanotechnology offers new possibilities for the design of vehicles for neuroprotection and neuroregeneration. Recent developments in nanoscale carriers for encapsulation and transport of BDNF are highlighted. PMID:24300402

  2. Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype

    DEFF Research Database (Denmark)

    da Silveira, W A; Palma, P V B; Sicchieri, R D

    2017-01-01

    Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis...... of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies....... and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression...

  3. Factors controlling the spatial distribution of soil piping erosion on loess-derived soils: A case study from central Belgium

    Science.gov (United States)

    Verachtert, E.; Van Den Eeckhaut, M.; Poesen, J.; Deckers, J.

    2010-06-01

    Collapsible loess-derived soils are prone to soil piping erosion, where enlargement of macropores may lead to a subsurface pipe network and eventually to soil collapse and gully development. This study aims at understanding the main factors controlling spatial patterns of piping in loess-derived soils under a temperate climate. To map the spatial distribution of piping and identify the environmental controls on its distribution, a regional survey was carried out in a 236 km 2 study area in the Flemish Ardennes (Belgium). Orthophotos taken at optimal field conditions (winter) were analyzed to detect piping in open landscapes and ground thruthing was systematically done through field surveys. In total, 137 parcels having 560 collapsed pipes were mapped. Dimensions of the sinkholes and local slope gradient were measured in the field and topographical variables were derived from LiDAR data. Land use plays an important role as 97% of the sites with piping are found under pasture. The probability of piping increases rapidly on hillslopes with gradients exceeding 8% and with a concave profile and plan curvature, enhancing subsurface flow concentration. The zones with soil profiles on shallow loess over a relatively thin layer of homogeneous blue massive clays (Aalbeke Member) are most prone to piping. Soil characteristics are of less importance to explain piping occurrence. Furthermore, the topographical threshold line indicating the critical slope gradient for a given contributing drainage area was determined. This threshold line (negative power relation) is similar to the threshold line for shallow gully initiation.

  4. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    International Nuclear Information System (INIS)

    Colleoni, Silvia; Galli, Cesare; Giannelli, Serena G.; Armentero, Marie-Therese; Blandini, Fabio; Broccoli, Vania; Lazzari, Giovanna

    2010-01-01

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  5. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    Energy Technology Data Exchange (ETDEWEB)

    Colleoni, Silvia, E-mail: silviacolleoni@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Galli, Cesare [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Dipartimento Clinico Veterinario, Universita di Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (Italy); Giannelli, Serena G. [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Armentero, Marie-Therese; Blandini, Fabio [Laboratory of Functional Neurochemistry, Interdepartmental Research Center for Parkinson' s Disease, Neurological Institute C. Mondino, Via Mondino 2, 27100 Pavia (Italy); Broccoli, Vania, E-mail: broccoli.vania@hsr.it [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Lazzari, Giovanna, E-mail: giovannalazzari@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy)

    2010-04-15

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  6. Field Derived Emission Factors For Formaldehyde and other Volatile Organic Compounds in FEMA Temporary Housing Units

    Energy Technology Data Exchange (ETDEWEB)

    Parthasarathy, Srinandini; Maddalena, Randy L.; Russell, Marion L.; Apte, Michael G.

    2010-10-01

    Sixteen previously occupied temporary housing units (THUs) were studied to assess emissions of volatile organic compounds. The whole trailer emission factors wereevaluated for 36 VOCs including formaldehyde. Indoor sampling was carried out in the THUs located in Purvis staging yard in Mississippi, USA. Indoor temperature andrelative humidity (RH) were also measured in all the trailers during sampling. Indoor temperatures were varied (increased or decreased) in a selection of THUs using theheating, ventilation and air conditioning (HVAC) systems. Indoor temperatures during sampling ranged from 14o C to 33o C, and relative humidity (RH) varied between 35percentand 74percent. Ventilation rates were increased in some trailers using bathroom fans and vents during some of the sampling events. Ventilation rates measured during some aselection of sampling events varied from 0.14 to 4.3 h-1. Steady state indoor formaldehyde concentrations ranged from 10 mu g-m-3 to 1000 mu g-m-3. The formaldehyde concentrations in the trailers were of toxicological significance. The effects of temperature, humidity and ventilation rates were also studied. A linearregression model was built using log of percentage relative humidity, inverse of temperature (in K-1), and inverse log ACH as continuous independent variables, trailermanufacturer as a categorical independent variable, and log of the chemical emission factors as the dependent variable. The coefficients of inverse temperature, log relativehumidity, log inverse ACH with log emission factor were found to be statistically significant for all the samples at the 95percent confidence level. The regression model wasfound to explain about 84percent of the variation in the dependent variable. Most VOC concentrations measured indoors in the Purvis THUs were mostly found to be belowvalues reported in earlier studies by Maddalena et al.,1,2 Hodgson et al.,3 and Hippelein4. Emissions of TMPB-DIB (a plasticizer found in vinyl products) were found

  7. Inhibitory effect of vitamin D-binding protein-derived macrophage activating factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived carcinoma cell line.

    Science.gov (United States)

    Toyohara, Yukiyo; Hashitani, Susumu; Kishimoto, Hiromitsu; Noguchi, Kazuma; Yamamoto, Nobuto; Urade, Masahiro

    2011-07-01

    This study investigated the inhibitory effect of vitamin D-binding protein-derived macrophage-activating factor (GcMAF) on carcinogenesis and tumor growth, using a 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced hamster cheek pouch carcinogenesis model, as well as the cytocidal effect of activated macrophages against HCPC-1, a cell line established from DMBA-induced cheek pouch carcinoma. DMBA application induced squamous cell carcinoma in all 15 hamsters of the control group at approximately 10 weeks, and all 15 hamsters died of tumor burden within 20 weeks. By contrast, 2 out of the 14 hamsters with GcMAF administration did not develop tumors and the remaining 12 hamsters showed a significant delay of tumor development for approximately 3.5 weeks. The growth of tumors formed was significantly suppressed and none of the hamsters died within the 20 weeks during which they were observed. When GcMAF administration was stopped at the 13th week of the experiment in 4 out of the 14 hamsters in the GcMAF-treated group, tumor growth was promoted, but none of the mice died within the 20-week period. On the other hand, when GcMAF administration was commenced after the 13th week in 5 out of the 15 hamsters in the control group, tumor growth was slightly suppressed and all 15 hamsters died of tumor burden. However, the mean survival time was significantly extended. GcMAF treatment activated peritoneal macrophages in vitro and in vivo, and these activated macrophages exhibited a marked cytocidal effect on HCPC-1 cells. Furthermore, the cytocidal effect of activated macrophages was enhanced by the addition of tumor-bearing hamster serum. These findings indicated that GcMAF possesses an inhibitory effect on tumor development and growth in a DMBA-induced hamster cheek pouch carcinogenesis model.

  8. On the incorrect derivation and use of in-situ retardation factors from natural isotope profiles

    International Nuclear Information System (INIS)

    McKinley, I.G.; Alexander, W.R.

    1996-01-01

    The characterization of the retardation of radionuclides during their transport by deep groundwaters is complex, time-consuming and, in many cases, inherently limited by technical problems. The stated goal of many natural analogue studies is thus the direct quantification of solute retardation in-situ in relevant geological environments. This paper reviews the claims for a methodology for determining in-situ retardation factors from a mathematical deconvolution of multiple radioisotope measurements of natural decay series elements. It is concluded that the assumptions involved in development of the mathematical approach are geochemically inconsistent and inapplicable to most geological systems of interest. Misapplications of this model are identified and the dangers of accepting its nonsensical output are discussed. (orig.)

  9. Apoptotic Effects of Reduced Brain Derived Neurotrophic Factor (BDNF on Mouse Liver and Kidney

    Directory of Open Access Journals (Sweden)

    Berna Tezcan

    2017-12-01

    Full Text Available Objective: Brainderived neurotrophic factor (BDNF promotes the development and differentiation of neurons and synapses, as well as neuronal survival, by acting on specific neuronal groups in the central and peripheral nervous systems. However, the direct effect of BDNF on apoptosis in peripheral tissues is not known. The aim of this study was to investigate the relationship between BDNF and apoptosis, and the density and distribution of BDNF receptors in liver and kidney tissues by histological and immunehistochemical methods. Methods: Seven wild-type and 7 BDNF heterozygous (reduced BDNF levels male mice were used in the study. Caspase-3 and TUNEL immunehistochemical stainings were performed in order to investigate the presence of apoptosis in the liver and kidney tissues of the studied groups. Apoptosis-entering cells were counted and the groups were compared. Concentration and distribution of BDNF receptors, tropomyosin-related kinase B (TrkB and nerve growth factor receptor p75 (NGFR p75, in liver and kidney tissues were also examined by immunehistochemical analyzes. Results: As a result of Caspase-3 and TUNEL immune histochemical staining, more cells were counted to enter the apoptotic process in sections of BDNF heterozygous group compared to control group (p<0.0001. In both groups TrkB and NGFR p75 receptors in liver and kidney tissues were determined in trace amounts, but there was no difference in intensity and distribution between the studied groups. Conclusion: According to our histological and immune histochemical stainings and statistical analysis of cell count between groups, it was found that BDNF is protect ive against apoptosis in liver and kidney. The lack of difference between the studied groups in terms of intensity and distribution of BDNF receptors, suggests that BDNF receptor distribution in the liver and kidney tissues may be different from the nervous system or that BDNF may differ in affinity for these receptors.

  10. Factor Structure of Indices of the Second Derivative of the Finger Photoplethysmogram with Metabolic Components and Other Cardiovascular Risk Indicators

    Directory of Open Access Journals (Sweden)

    Tomoyuki Kawada

    2013-02-01

    Full Text Available BackgroundThe second derivative of the finger photoplethysmogram (SDPTG is an indicator of arterial stiffness. The present study was conducted to clarify the factor structure of indices of the SDPTG in combination with components of the metabolic syndrome (MetS, to elucidate the significance of the SDPTG among various cardiovascular risk factors.MethodsThe SDPTG was determined in the second forefinger of the left hand in 1,055 male workers (mean age, 44.2±6.4 years. Among 4 waves of SDPTG components, the ratios of the height of the "a" wave to that of the "b" and "d" waves were expressed as b/a and d/a, and used as SDPTG indices for the analysis.ResultsPrincipal axis factoring analysis was conducted using age, SDPTG indices, components of MetS, and the serum levels of C-reactive protein (CRP and uric acid. Three factors were extracted, and the SDPTG indices were categorized in combination with age as the third factor. Metabolic components and the SDPTG indices were independently categorized. These three factors explained 44.4% of the total variation. Multiple logistic regression analysis revealed age, d/a, serum uric acid, serum CRP, and regular exercise as independent determinants of the risk of MetS. The odds ratios (95% confidence intervals were 1.08 (1.04 to 1.11, 0.10 (0.01 to 0.73, 1.24 (1.06 to 1.44, 3.59 (2.37 to 5.42, and 0.48 (0.28 to 0.82, respectively.ConclusionThe SDPTG indices were categorized in combination with age, and they differed in characteristics from components of MetS or inflammatory markers. In addition, this cross-sectional study also revealed decrease of the d/a as a risk factor for the development of MetS.

  11. Factors affecting antimicrobial activity of MUC7 12-mer, a human salivary mucin-derived peptide

    Directory of Open Access Journals (Sweden)

    Bobek Libuse A

    2007-11-01

    Full Text Available Abstract Background MUC7 12-mer (RKSYKCLHKRCR, a cationic antimicrobial peptide derived from the human low-molecular-weight salivary mucin MUC7, possesses potent antimicrobial activity in vitro. In order to evaluate the potential therapeutic application of the MUC7 12-mer, we examined the effects of mono- and divalent cations, EDTA, pH, and temperature on its antimicrobial activity. Methods Minimal Inhibitory Concentrations (MICs were determined using a liquid growth inhibition assay in 96-well microtiter plates. MUC7 12-mer was added at concentrations of 1.56–50 μM. MICs were determined at three endpoints: MIC-0, MIC-1, and MIC-2 (the lowest drug concentration showing 10%, 25% and 50% of growth, respectively. To examine the effect of salts or EDTA, a checkerboard microdilution technique was used. Fractional inhibitory concentration index (FICi was calculated on the basis of MIC-0. The viability of microbial cells treated with MUC7 12-mer in the presence of sodium or potassium was also determined by killing assay or flow cytometry. Results The MICs of MUC7 12-mer against organisms tested ranged from 6.25–50 μM. For C. albicans, antagonism (FICi 4.5 was observed for the combination of MUC7 12-mer and calcium; however, there was synergism (FICi 0.22 between MUC7 12-mer and EDTA, and the synergism was retained in the presence of calcium at its physiological concentration (1–2 mM. No antagonism but additivity or indifference (FICi 0.55–2.5 was observed for the combination of MUC7 12-mer and each K+, Na+, Mg2+, or Zn2+. MUC7 12-mer peptide (at 25 μM also exerted killing activity in the presence of NaCl, (up to 25 mM for C. albicans and up to 150 mM for E. coli, a physiological concentration of sodium in the oral cavity and serum, respectively and retained candidacidal activity in the presence of KCl (up to 40 mM. The peptide exhibited higher inhibitory activity against C. albicans at pH 7, 8, and 9 than at pH 5 and 6, and temperature up to

  12. Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Biaoru Li

    Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

  13. Measurements of humidified particle number size distributions in a Finnish boreal forest: derivation of hygroscopic particle growth factors

    Energy Technology Data Exchange (ETDEWEB)

    Birmili, W.; Schwirn, K.; Nowak, A.; Rose, D.; Wiedensohler, A. (Leibniz Institute for Tropospheric Research, Leipzig (Germany)); Petaejae, T.; Haemeri, K.; Aalto, P.; Kulmala, M.; Boy, M. (Dept. of Physics, Univ. of Helsinki (Finland)); Joutsensaari, J. (Univ. of Kuopio, Dept. of Physics (Finland))

    2009-07-01

    Dry and humidified size distributions of atmospheric particles were characterised at the atmospheric research station SMEAR 2, Finland between May and July 2004. Particles were classified in a size range between 3 and 800 nm at controlled relative humidities up to 90% by two instruments complementary in size range (HDMPS; Nano-HDMPS). Using the summation method, descriptive hygroscopic growth factors (DHGF) were derived for particle diameters between 70 and 300 nm by comparing dry and humidified size distributions. At 90% relative humidity, DHGF showed mean values between 1.25 and 1.45 in the accumulation mode, between 1.20 and 1.25 in the Aitken mode, and between 1.15 and 1.20 in the nucleation mode. Due to the high size resolution of the method, the transition in DHGF between the Aitken and accumulation modes, which reflects differences in the soluble fraction, could be pinpointed efficiently. For the accumulation mode, experimental DHGFs were compared to those calculated from a simplistic growth model initialised by in-situ chemical composition measurements, and yielded maximum deviations around 0.1. The variation in DHGF could only imperfectly be linked to meteorological factors. A pragmatic parameterisation of DHGF as a function of particle diameter and relative humidity was derived, and subsequently used to study the sensitivity of the condensational sink parameter (CS) as a function of height in a well-mixed boundary layer. (orig.)

  14. The role of tumor cell-derived connective tissue growth factor (CTGF/CCN2) in pancreatic tumor growth.

    Science.gov (United States)

    Bennewith, Kevin L; Huang, Xin; Ham, Christine M; Graves, Edward E; Erler, Janine T; Kambham, Neeraja; Feazell, Jonathan; Yang, George P; Koong, Albert; Giaccia, Amato J

    2009-02-01

    Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA-expressing clones showed dramatically reduced growth in soft agar and when implanted s.c. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by positron emission tomography imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed colocalization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell-derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer.

  15. Macrophage-derived insulin-like growth factor-1 affects influenza vaccine efficacy through the regulation of immune cell homeostasis.

    Science.gov (United States)

    Yoon, Il-Sub; Park, Hyelim; Kwak, Hye-Won; Woo Jung, Yong; Nam, Jae-Hwan

    2017-08-24

    The level of antibody production induced by a vaccine involves a variety of host factors. One of these, insulin-like growth factor-1 (IGF-1), plays an important role in lymphocyte maturation and antibody expression. Here, we investigated the role of macrophage-derived IGF-1 in the induction of influenza vaccine-specific antibodies using macrophage-derived IGF-1 gene knockout (MIKO) mice. The titers of vaccine-specific total immunoglobulin G (IgG) and IgG1 after immunization were about two- to fourfold lower in MIKO mice than in WT mice. Moreover, MIKO mice showed a relatively weak booster effect of repeated immunization. In contrast, antigen-nonspecific total IgG was about threefold higher in MIKO mice than in WT mice. After viral challenge, the viral titer and the pathological damage in lungs of MIKO mice were higher than those in WT mice despite vaccination. Interestingly, the proportions of proinflammatory immune cells including M1 macrophages, Th1 and Th17 cells was higher in unvaccinated MIKO mice than in unvaccinated WT mice. This suggests that nonspecific activation of immune cells may paradoxically impair the response to the vaccine. In addition, although the proportions of T follicular helper (Tfh) cells and GL-7 + germinal center (GC) B cells were higher in MIKO mice than in WT mice, the population of CD138 + B220 + antibody-secreting plasmablasts was lower in MIKO mice, which may be a cause of the low influenza-specific antibody titer in MIKO mice. Taken together, these results suggest that macrophage-derived IGF-1 might play an important role in the vaccine-triggered immune response by regulating immune cell homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults.

    Science.gov (United States)

    Azeredo, Lucas A de; De Nardi, Tatiana; Levandowski, Mateus L; Tractenberg, Saulo G; Kommers-Molina, Julia; Wieck, Andrea; Irigaray, Tatiana Q; Silva, Irênio G da; Grassi-Oliveira, Rodrigo

    2017-01-01

    Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

  17. Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

    Science.gov (United States)

    Das, Undurti N

    2013-10-01

    Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. NANOS2 acts downstream of glial cell line-derived neurotrophic factor signaling to suppress differentiation of spermatogonial stem cells.

    Science.gov (United States)

    Sada, Aiko; Hasegawa, Kazuteru; Pin, Pui Han; Saga, Yumiko

    2012-02-01

    Stem cells are maintained by both stem cell-extrinsic niche signals and stem cell-intrinsic factors. During murine spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) signal emanated from Sertoli cells and germ cell-intrinsic factor NANOS2 represent key regulators for the maintenance of spermatogonial stem cells. However, it remains unclear how these factors intersect in stem cells to control their cellular state. Here, we show that GDNF signaling is essential to maintain NANOS2 expression, and overexpression of Nanos2 can alleviate the stem cell loss phenotype caused by the depletion of Gfra1, a receptor for GDNF. By using an inducible Cre-loxP system, we show that NANOS2 expression is downregulated upon the conditional knockout (cKO) of Gfra1, while ectopic expression of Nanos2 in GFRA1-negative spermatogonia does not induce de novo GFRA1 expression. Furthermore, overexpression of Nanos2 in the Gfra1-cKO testes prevents precocious differentiation of the Gfra1-knockout stem cells and partially rescues the stem cell loss phenotypes of Gfra1-deficient mice, indicating that the stem cell differentiation can be suppressed by NANOS2 even in the absence of GDNF signaling. Taken together, we suggest that NANOS2 acts downstream of GDNF signaling to maintain undifferentiated state of spermatogonial stem cells. Copyright © 2011 AlphaMed Press.

  19. The brain-derived neurotrophic factor (BDNF gene Val66Met polymorphism affects memory performance in older adults

    Directory of Open Access Journals (Sweden)

    Lucas A. de Azeredo

    Full Text Available Objective: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Methods: Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR, delayed verbal recall (DVR, and memory retention rate. Results: BDNF Met allele carriers had lower DVR scores (p = 0.004 and a decline in memory retention (p = 0.017 when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088. Conclusion: These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

  20. Impact of Environmental Factors on Bacteriocin Promoter Activity in Gut-Derived Lactobacillus salivarius.

    Science.gov (United States)

    Guinane, Caitriona M; Piper, Clare; Draper, Lorraine A; O'Connor, Paula M; Hill, Colin; Ross, R Paul; Cotter, Paul D

    2015-11-01

    Bacteriocin production is regarded as a desirable probiotic trait that aids in colonization and persistence in the gastrointestinal tract (GIT). Strains of Lactobacillus salivarius, a species associated with the GIT, are regarded as promising probiotic candidates and have a number of associated bacteriocins documented to date. These include multiple class IIb bacteriocins (salivaricin T, salivaricin P, and ABP-118) and the class IId bacteriocin bactofencin A, which show activity against medically important pathogens. However, the production of a bacteriocin in laboratory media does not ensure production under stressful environmental conditions, such as those encountered within the GIT. To allow this issue to be addressed, the promoter regions located upstream of the structural genes encoding the L. salivarius bacteriocins mentioned above were fused to a number of reporter proteins (green fluorescent protein [GFP], red fluorescent protein [RFP], and luciferase [Lux]). Of these, only transcriptional fusions to GFP generated signals of sufficient strength to enable the study of promoter activity in L. salivarius. While analysis of the class IIb bacteriocin promoter regions indicated relatively weak GFP expression, assessment of the promoter of the antistaphylococcal bacteriocin bactofencin A revealed a strong promoter that is most active in the absence of the antimicrobial peptide and is positively induced in the presence of mild environmental stresses, including simulated gastric fluid. Taken together, these data provide information on factors that influence bacteriocin production, which will assist in the development of strategies to optimize in vivo and in vitro production of these antimicrobials. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors

    Science.gov (United States)

    Ahmed, Muhammad S.; Rainer, Carolyn; Nielsen, Sebastian R.; Quaranta, Valeria; Weyer-Czernilofsky, Ulrike; Engle, Danielle D.; Perez-Mancera, Pedro A.; Coupland, Sarah E.; Taktak, Azzam; Bogenrieder, Thomas; Tuveson, David A.; Campbell, Fiona; Schmid, Michael C.; Mielgo, Ainhoa

    2017-01-01

    Tumor-associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors (IGF) 1 and 2, which activate insulin/IGF receptors on pancreatic cancer cells. Immunohistochemical analysis of biopsies from patients with pancreatic cancer revealed that 72% of the patients expressed activated insulin/IGF receptors on tumor cells, and this positively correlates with increased CD163+ TAM infiltration. In vivo, we found that TAM and myofibroblasts were the main sources of IGF production, and pharmacologic blockade of IGF sensitized pancreatic tumors to gemcitabine. These findings suggest that inhibition of IGF in combination with chemotherapy could benefit patients with PDAC, and that insulin/IGF1R activation may be used as a biomarker to identify patients for such therapeutic intervention. PMID:27742686

  2. Platelet-activating factor dilates efferent arterioles through glomerulus-derived nitric oxide.

    Science.gov (United States)

    Arima, S; Ren, Y; Juncos, L A; Ito, S

    1996-01-01

    Despite evidence that platelet-activating factor (PAF) is produced by the glomerulus, its direct action on the glomerular microcirculation is poorly understood. It was recently reported that at picomolar concentrations, PAF dilates isolated microperfused afferent arterioles (Af-Art) via nitric oxide (NO). The present study tested the hypothesis that PAF acts on the glomerulus to release NO, which in turn controls the resistance of the efferent arteriole (Ef-Art). Rabbit Ef-Art were perfused from the distal end (retrograde perfusion [RP]) to eliminate the influence of the glomerulus, or through the glomerulus from the end of the Af-Art (orthograde perfusion [OP]) to maintain the influence of the glomerulus. Ef-Art were preconstricted by approximately 40% with norepinephrine and increasing doses of PAF were added to both the arteriolar perfusate and bath. Only with OP did PAF at picomolar concentrations cause significant dilation: at 400 pmol, the diameter increased by 64 +/- 11% from the preconstricted level (N = 6, P Art. At nanomolar concentrations, PAF constricted Ef-Art similarly in both RP and OP: at 40 nM, the diameter decreased by 24 +/- 4% (N = 6, P OP (10 +/- 2%, N = 6; P Art; and (2) at nanomolar concentrations, PAF constricts the Ef-Art partly through release of cyclooxygenase metabolites. Thus, PAF may play a role in glomerular hemodynamics under various physiological and pathological conditions.

  3. Plant-Derived Transcription Factors for Orthologous Regulation of Gene Expression in the Yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Naseri, Gita; Balazadeh, Salma; Machens, Fabian; Kamranfar, Iman; Messerschmidt, Katrin; Mueller-Roeber, Bernd

    2017-09-15

    Control of gene expression by transcription factors (TFs) is central in many synthetic biology projects for which a tailored expression of one or multiple genes is often needed. As TFs from evolutionary distant organisms are unlikely to affect gene expression in a host of choice, they represent excellent candidates for establishing orthogonal control systems. To establish orthogonal regulators for use in yeast (Saccharomyces cerevisiae), we chose TFs from the plant Arabidopsis thaliana. We established a library of 106 different combinations of chromosomally integrated TFs, activation domains (yeast GAL4 AD, herpes simplex virus VP64, and plant EDLL) and synthetic promoters harboring cognate cis-regulatory motifs driving a yEGFP reporter. Transcriptional output of the different driver/reporter combinations varied over a wide spectrum, with EDLL being a considerably stronger transcription activation domain in yeast than the GAL4 activation domain, in particular when fused to Arabidopsis NAC TFs. Notably, the strength of several NAC-EDLL fusions exceeded that of the strong yeast TDH3 promoter by 6- to 10-fold. We furthermore show that plant TFs can be used to build regulatory systems encoded by centromeric or episomal plasmids. Our library of TF-DNA binding site combinations offers an excellent tool for diverse synthetic biology applications in yeast.

  4. Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation

    International Nuclear Information System (INIS)

    Sedlmaier, Angela; Wernert, Nicolas; Gallitzendörfer, Rainer; Abouzied, Mekky M; Gieselmann, Volkmar; Franken, Sebastian

    2011-01-01

    HDGF is a growth factor which is overexpressed in a wide range of tumors. Importantly, expression levels were identified as a prognostic marker in some types of cancer such as melanoma. To investigate the presumed oncogenic/transforming capacity of HDGF, we generated transgenic mice overexpressing HDGF in melanocytes. These mice were bred with mice heterozygous for a defective copy of the Ink4a tumor suppressor gene and were exposed to UV light to increase the risk for tumor development both genetically and physiochemically. Mice were analyzed by immunohistochemistry and Western blotting. Furthermore, primary melanocytes were isolated from different strains created. Transgenic animals overexpressed HDGF in hair follicle melanocytes. Interestingly, primary melanocytes isolated from transgenic animals were not able to differentiate in vitro whereas cells isolated from wild type and HDGF-deficient animals were. Although, HDGF -/- /Ink4a +/- mice displayed an increased number of epidermoid cysts after exposure to UV light, no melanomas or premelanocytic alterations could be detected in this mouse model. The results therefore provide no evidence that HDGF has a transforming capacity in tumor development. Our results in combination with previous findings point to a possible role in cell differentiation and suggest that HDGF promotes tumor progression after secondary upregulation and may represent another protein fitting into the concept of non-oncogene addiction of tumor tissue

  5. Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors.

    Science.gov (United States)

    Cui, Jing; Peng, Xia; Gao, Dingding; Dai, Yang; Ai, Jing; Li, Yingxia

    2017-08-15

    Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy because of its critical role in promoting cancer formation and progression. In a continuing effort to improve the cellular activity of hit compound 7r bearing an indazole scaffold, which was previously discovered by our group, several compounds harnessing fluorine substituents were designed, synthesized and biological evaluated. Besides, the region extended out to the ATP binding pocket toward solvent was also explored. Among them, compound 2a containing 2,6-difluoro-3-methoxyphenyl residue exhibited the most potent activities (FGFR1: less than 4.1nM, FGFR2: 2.0±0.8nM). More importantly, compound 2a showed an improved antiproliferative effect against KG1 cell lines and SNU16 cell lines with IC 50 values of 25.3±4.6nM and 77.4±6.2nM respectively. Copyright © 2017. Published by Elsevier Ltd.

  6. Identification of anthranilamide derivatives as potential factor Xa inhibitors: drug design, synthesis and biological evaluation.

    Science.gov (United States)

    Xing, Junhao; Yang, Lingyun; Li, Hui; Li, Qing; Zhao, Leilei; Wang, Xinning; Zhang, Yuan; Zhou, Muxing; Zhou, Jinpei; Zhang, Huibin

    2015-05-05

    The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against fXa. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 μM). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 × PT value of 8.7 μM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF.

    Science.gov (United States)

    Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

    2008-07-01

    Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years.

  8. Platelet-derived growth factor (PDGF) stimulates glycogen synthase activity in 3T3 cells

    International Nuclear Information System (INIS)

    Chan, C.P.; Bowen-Pope, D.F.; Ross, R.; Krebs, E.G.

    1986-01-01

    Hormonal regulation of glycogen synthase, an enzyme that can be phosphorylated on multiple sites, is often associated with changes in its phosphorylation state. Enzyme activation is conventionally monitored by determining the synthase activity ratio [(activity in the absence of glucose 6-P)/(activity in the presence of glucose 6-P)]. Insulin causes an activation of glycogen synthase with a concomitant decrease in its phosphate content. In a previous report, the authors showed that epidermal growth factor (EGF) increases the glycogen synthase activity ratio in Swiss 3T3 cells. The time and dose-dependency of this response was similar to that of insulin. Their recent results indicate that PDGF also stimulates glycogen synthase activity. Enzyme activation was maximal after 30 min. of incubation with PDGF; the time course observed was very similar to that with insulin and EGF. At 1 ng/ml (0.03nM), PDGF caused a maximal stimulation of 4-fold in synthase activity ratio. Half-maximal stimulation was observed at 0.2 ng/ml (6 pM). The time course of changes in enzyme activity ratio closely followed that of 125 I-PDGF binding. The authors data suggest that PDGF, as well as EFG and insulin, may be important in regulating glycogen synthesis through phosphorylation/dephosphorylation mechanisms

  9. On Radiative Factors in Planetary Rings: New Insight Derived from Cassini CIRS Observations at Saturn Equinox

    Science.gov (United States)

    Brooks, S. M.; Spilker, L. J.; Pilorz, S.; Edgington, S. G.; Deau, E.; Morishima, R.

    2012-12-01

    Since arriving at Saturn in 2004, Cassini's Composite Infrared Spectrometer has recorded tens of millions of spectra of Saturn's rings (personal communication, M. Segura). CIRS records far infrared radiation (16.7-1000 microns) at focal plane 1 (FP1). Thermal emission from Saturn's rings peaks at FP1 wavelengths. CIRS spectra are well characterized as blackbody emission at an effective temperature Te, multiplied by a scalar factor related to ring emissivity (Spilker et al. [2005, 2006]). CIRS can therefore characterize the rings' temperature and study the thermal environment to which the ring particles are subject. We focus on CIRS data from the 2009 Saturnian equinox. As the Sun's disk crossed the ring plane, CIRS obtained several radial scans of the rings at a variety of phase angles, local hour angles and distances. With the Sun's rays striking the rings at an incidence angle of zero, solar heating is virtually absent, and thermal radiation from Saturn and sunlight reflected by Saturn dominate the thermal environment. These observations appear to present a paradox. Equinox data show that the flux of thermal energy radiated by the rings can even exceed the energy incident upon them as prescribed by thermal models, particularly in the C ring and Cassini Division (Ferrari and Leyrat [2006], Morishima et al. [2009, 2010]). Conservation principles suggest that such models underestimate heating of the rings in these cases, as it is clearly unphysical for the rings to radiate significantly more energy than is incident upon them. In this presentation, we will describe our efforts to resolve this paradox and determine what doing so can teach us about Saturn's rings. This research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under contract with NASA. Copyright 2012 California Institute of Technology. Government sponsorship acknowledged.

  10. Postresuscitative Changes of Brain-Derived Neurotrophic Factor (BDNF Protein Expression: Association With Neuronal Death

    Directory of Open Access Journals (Sweden)

    M. Sh. Avrushchenko

    2017-01-01

    populations. The results suggest that the level of BDNF expression is one of factors that have a significant effect on neuronal resistance to ischemia-reperfusion. A possibility of induction of the endogenous BDNF expression in order to prevent neuronal death is discussed. 

  11. Neer Award 2018: Platelet-derived growth factor receptor α co-expression typifies a subset of platelet-derived growth factor receptor β-positive progenitor cells that contribute to fatty degeneration and fibrosis of the murine rotator cuff.

    Science.gov (United States)

    Jensen, Andrew R; Kelley, Benjamin V; Mosich, Gina M; Ariniello, Allison; Eliasberg, Claire D; Vu, Brandon; Shah, Paras; Devana, Sai K; Murray, Iain R; Péault, Bruno; Dar, Ayelet; Petrigliano, Frank A

    2018-04-10

    After massive tears, rotator cuff muscle often undergoes atrophy, fibrosis, and fatty degeneration. These changes can lead to high surgical failure rates and poor patient outcomes. The identity of the progenitor cells involved in these processes has not been fully elucidated. Platelet-derived growth factor receptor β (PDGFRβ) and platelet-derived growth factor receptor α (PDGFRα) have previously been recognized as markers of cells involved in muscle fibroadipogenesis. We hypothesized that PDGFRα expression identifies a fibroadipogenic subset of PDGFRβ + progenitor cells that contribute to fibroadipogenesis of the rotator cuff. We created massive rotator cuff tears in a transgenic strain of mice that allows PDGFRβ + cells to be tracked via green fluorescent protein (GFP) fluorescence. We then harvested rotator cuff muscle tissues at multiple time points postoperatively and analyzed them for the presence and localization of GFP + PDGFRβ + PDGFRα + cells. We cultured, induced, and treated these cells with the molecular inhibitor CWHM-12 to assess fibrosis inhibition. GFP + PDGFRβ + PDGFRα + cells were present in rotator cuff muscle tissue and, after massive tears, localized to fibrotic and adipogenic tissues. The frequency of PDGFRβ + PDGFRα + cells increased at 5 days after massive cuff tears and decreased to basal levels within 2 weeks. PDGFRβ + PDGFRα + cells were highly adipogenic and significantly more fibrogenic than PDGFRβ + PDGFRα - cells in vitro and localized to adipogenic and fibrotic tissues in vivo. Treatment with CWHM-12 significantly decreased fibrogenesis from PDGFRβ + PDGFRα + cells. PDGFRβ + PDGFRα + cells directly contribute to fibrosis and fatty degeneration after massive rotator cuff tears in the mouse model. In addition, CWHM-12 treatment inhibits fibrogenesis from PDGFRβ + PDGFRα + cells in vitro. Clinically, perioperative PDGFRβ + PDGFRα + cell inhibition may limit rotator cuff tissue degeneration and, ultimately

  12. Derivatives of Dictyostelium differentiation-inducing factors inhibit lysophosphatidic acid–stimulated migration of murine osteosarcoma LM8 cells

    Energy Technology Data Exchange (ETDEWEB)

    Kubohara, Yuzuru, E-mail: ykuboha@juntendo.ac.jp [Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 371-8512 (Japan); Department of Health Science, Juntendo University Graduate School of Health and Sports Science, Inzai 270-1695 (Japan); Komachi, Mayumi [Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 371-8512 (Japan); Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Homma, Yoshimi [Department of Biomolecular Science, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295 (Japan); Kikuchi, Haruhisa; Oshima, Yoshiteru [Laboratory of Natural Product Chemistry, Tohoku University Graduate School of Pharmaceutical Sciences, Aoba-yama, Aoba-ku, Sendai 980-8578 (Japan)

    2015-08-07

    Osteosarcoma is a common metastatic bone cancer that predominantly develops in children and adolescents. Metastatic osteosarcoma remains associated with a poor prognosis; therefore, more effective anti-metastatic drugs are needed. Differentiation-inducing factor-1 (DIF-1), −2, and −3 are novel lead anti-tumor agents that were originally isolated from the cellular slime mold Dictyostelium discoideum. Here we investigated the effects of a panel of DIF derivatives on lysophosphatidic acid (LPA)-induced migration of mouse osteosarcoma LM8 cells by using a Boyden chamber assay. Some DIF derivatives such as Br-DIF-1, DIF-3(+2), and Bu-DIF-3 (5–20 μM) dose-dependently suppressed LPA-induced cell migration with associated IC{sub 50} values of 5.5, 4.6, and 4.2 μM, respectively. On the other hand, the IC{sub 50} values of Br-DIF-1, DIF-3(+2), and Bu-DIF-3 versus cell proliferation were 18.5, 7.2, and 2.0 μM, respectively, in LM8 cells, and >20, 14.8, and 4.3 μM, respectively, in mouse 3T3-L1 fibroblasts (non-transformed). Together, our results demonstrate that Br-DIF-1 in particular may be a valuable tool for the analysis of cancer cell migration, and that DIF derivatives such as DIF-3(+2) and Bu-DIF-3 are promising lead anti-tumor agents for the development of therapies that suppress osteosarcoma cell proliferation, migration, and metastasis. - Highlights: • LPA induces cell migration (invasion) in murine osteosarcoma LM8 cells. • DIFs are novel lead anti-tumor agents found in Dictyostelium discoideum. • We examined the effects of DIF derivatives on LPA-induced LM8 cell migration in vitro. • Some of the DIF derivatives inhibited LPA-induced LM8 cell migration.

  13. Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment

    NARCIS (Netherlands)

    Molendijk, M.L.; Bus, B.A.A.; Spinhoven, P.; Penninx, B.W.J.H.; Kenis, G.; Prickaerts, J.; Voshaar, R.C.O.; Elzinga, B.M.

    2011-01-01

    Recent evidence supports 'the neurotrophin hypothesis of depression' in its prediction that brain-derived neurotrophic factor (BDNF) is involved in depression. However, some key questions remain unanswered, including whether abnormalities in BDNF persist beyond the clinical state of depression,

  14. The Expanding Family of Bone Marrow Homing Factors for Hematopoietic Stem Cells: Stromal Derived Factor 1 Is Not the Only Player in the Game

    Directory of Open Access Journals (Sweden)

    Mariusz Z. Ratajczak

    2012-01-01

    Full Text Available The α-chemokine stromal derived factor 1 (SDF-1, which binds to the CXCR4 and CXCR7 receptors, directs migration and homing of CXCR4+ hematopoietic stem/progenitor cells (HSPCs to bone marrow (BM and plays a crucial role in retention of these cells in stem cell niches. However, this unique role of SDF-1 has been recently challenged by several observations supporting SDF-1-CXCR4-independent BM homing. Specifically, it has been demonstrated that HSPCs respond robustly to some bioactive lipids, such as sphingosine-1-phosphate (S1P and ceramide-1-phosphate (C1P, and migrate in response to gradients of certain extracellular nucleotides, including uridine triphosphate (UTP and adenosine triphosphate (ATP. Moreover, the responsiveness of HSPCs to an SDF-1 gradient is enhanced by some elements of innate immunity (e.g., C3 complement cascade cleavage fragments and antimicrobial cationic peptides, such as cathelicidin/LL-37 or β2-defensin as well as prostaglandin E2 (PGE2. Since all these factors are upregulated in BM after myeloblative conditioning for transplantation, a more complex picture of homing emerges that involves several factors supporting, and in some situations even replacing, the SDF-1-CXCR4 axis.

  15. Brain-Derived Neurotrophic Factor Elevates Activating Transcription Factor 4 (ATF4 in Neurons and Promotes ATF4-Dependent Induction of Sesn2

    Directory of Open Access Journals (Sweden)

    Jin Liu

    2018-03-01

    Full Text Available Activating transcription factor 4 (ATF4 plays important physiologic roles in the brain including regulation of learning and memory as well as neuronal survival and death. Yet, outside of translational regulation by the eIF2α-dependent stress response pathway, there is little information about how its levels are controlled in neurons. Here, we show that brain-derived neurotrophic factor (BDNF promotes a rapid and sustained increase in neuronal ATF4 transcripts and protein levels. This increase is dependent on tropomyosin receptor kinase (TrkB signaling, but independent of levels of phosphorylated eIF2α. The elevation in ATF4 protein occurs both in nuclei and processes. Transcriptome analysis revealed that ATF4 mediates BDNF-promoted induction of Sesn2 which encodes Sestrin2, a protector against oxidative and genotoxic stresses and a mTor complex 1 inhibitor. In contrast, BDNF-elevated ATF4 did not affect expression of a number of other known ATF4 targets including several with pro-apoptotic activity. The capacity of BDNF to elevate neuronal ATF4 may thus represent a means to maintain this transcription factor at levels that provide neuroprotection and optimal brain function without risk of triggering neurodegeneration.

  16. Observations on human smooth muscle cell cultures from hyperplastic lesions of prosthetic bypass grafts: Production of a platelet-derived growth factor-like mitogen and expression of a gene for a platelet-derived growth factor receptor--a preliminary study

    International Nuclear Information System (INIS)

    Birinyi, L.K.; Warner, S.J.; Salomon, R.N.; Callow, A.D.; Libby, P.

    1989-01-01

    Prosthetic bypass grafts placed to the distal lower extremity often fail because of an occlusive tissue response in the perianastomotic region. The origin of the cells that comprise this occlusive lesion and the causes of the cellular proliferation are not known. To increase our understanding of this process we cultured cells from hyperplastic lesions obtained from patients at the time of reexploration for lower extremity graft failure, and we studied their identity and growth factor production in tissue culture. These cultures contain cells that express muscle-specific actin isoforms, shown by immunohistochemical staining, consistent with vascular smooth muscle origin. These cultures also released material that stimulated smooth muscle cell growth. A portion of this activity was similar to platelet-derived growth factor, since preincubation with antibody-to-human platelet-derived growth factor partially blocked the mitogenic effect of medium conditioned by human anastomotic hyperplastic cells. These conditioned media also contained material that competed with platelet-derived growth factor for its receptor, as measured in a radioreceptor assay. Northern blot analysis showed that these cells contain messenger RNA that encodes the A chain but not the B chain of platelet-derived growth factor. In addition, these cells contain messenger RNA that encodes a platelet-derived growth factor receptor. We conclude that cultured smooth muscle cells from human anastomotic hyperplastic lesions express genes for platelet-derived growth factor A chain and a platelet-derived growth factor receptor and secrete biologically active molecules similar to platelet-derived growth factor

  17. Platelet-Derived Growth Factor (PDGF/PDGF Receptors (PDGFR Axis as Target for Antitumor and Antiangiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Anca Maria Cimpean

    2010-03-01

    Full Text Available Angiogenesis in normal and pathological conditions is a multi-step process governed by positive and negative endogenous regulators. Many growth factors are involved in different steps of angiogenesis, like vascular endothelial growth factors (VEGF, fibroblast growth factor (FGF-2 or platelet-derived growth factors (PDGF. From these, VEGF and FGF-2 were extensively investigated and it was shown that they significantly contribute to the induction and progression of angiogenesis. A lot of evidence has been accumulated in last 10 years that supports the contribution of PDGF/PDGFR axis in developing angiogenesis in both normal and tumoral conditions. The crucial role of PDGF-B and PDGFR-β in angiogenesis has been demonstrated by gene targeting experiments, and their expression correlates with increased vascularity and maturation of the vascular wall. PDGF and their receptors were identified in a large variety of human tumor cells. In experimental models it was shown that inhibition of PDGF reduces interstitial fluid pressure in tumors and enhances the effect of chemotherapy. PDGFR have been involved in the cardiovascular development and their loss leads to a disruption in yolk sac blood vessels development. PDGFRβ expression by pericytes is necessary for their recruitment and integration in the wall of tumor vessels. Endothelial cells of tumor-associated blood vessels can express PDGFR. Based on these data, it was suggested the potential benefit of targeting PDGFR in the treatment of solid tumors. The molecular mechanisms of PDGF/PDGFR-mediated angiogenesis are not fully understood, but it was shown that tyrosine kinase inhibitors reduce tumor growth and angiogenesis in experimental xenograft models, and recent data demonstrated their efficacy in chemoresistant tumors. The in vivo effects of PDGFR inhibitors are more complex, based on the cross-talk with other angiogenic factors. In this review, we summarize data regarding the mechanisms and

  18. The Oligo Fucoidan Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation of Airway Smooth Muscle Cells

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    Chao-Huei Yang

    2016-01-01

    Full Text Available In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05. Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%–99% after 48 h (p < 0.05 and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2, Akt, and nuclear factor (NF-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials.

  19. Vildagliptin reduces plasma stromal cell-derived factor-1α in patients with type 2 diabetes compared with glimepiride.

    Science.gov (United States)

    Park, Kyeong Seon; Kwak, SooHeon; Cho, Young Min; Park, Kyong Soo; Jang, Hak C; Kim, Seong Yeon; Jung, Hye Seung

    2017-03-01

    Dipeptidyl peptidase-4 inhibitors might have pleiotropic protective effects on cardiovascular disease (CVD), in contrast to sulfonylureas. Therefore, we compared various CVD risk factors between vildagliptin and glimepiride. We carried out a randomized, prospective and crossover trial. A total of 16 patients with type 2 diabetes whose glycated hemoglobin was >7% were randomized to add vildagliptin or glimepiride. After 12-week treatment, each drug was replaced with the other for another 12 weeks. Before and after each treatment, glucose homeostasis and CVD risk factors were assessed, and the continuous glucose monitoring system was applied to calculate glycemic variability. The mean age of the participants was 60 years, 31% were men, body mass index 25.5 kg/m 2 and HbA1c 8.41%. Both vildagliptin and glimepiride significantly decreased glycated hemoglobin and glycemic variability indices. Despite the improved glucose homeostasis, favorable change of CVD markers was not prominent in both the arms, along with significant weight gain. Only plasma stromal cell-derived factor (SDF)-1α decreased by 30% in the vildagliptin arm. According to regression analyses, the reduction of SDF-1α was independently associated with vildagliptin usage and serum interleukin-6 changes, but white blood cells were not related with the SDF-1α changes. Compared with glimepiride, vildagliptin arrestingly decreased plasma SDF-1α, and its clinical implications should be further investigated. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  20. Cardiac regeneration by pharmacologically active microcarriers releasing growth factors and/or transporting adipose-derived stem cells

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    Monia Savi

    2014-01-01

    Full Text Available We tested the hypothesis that cardiac regeneration through local delivery of adipose-derived stem cells (ASCs, activation of resident cardiac stem cells via growth factors (GFs [hepatocyte growth factor (HGF and insulin-like growth factor 1 (IGF-1:GFs] or both, are improved by pharmacologically active microcarriers (PAMs interacting with cells/molecules conveyed on their surface. Rats with one-month old myocardial infarction were treated with ASCs, ASCs+PAMs, GF-releasing PAMs, ASCs+GF-releasing PAMs or vehicle. Two weeks later, hemodynamic function and inducibility of ventricular arrhythmias (VAs were assessed. Eventually, the hearts were subjected to anatomical and immunohistochemical analyses. A significant ASCs engraftment and the largest improvement in cardiac mechanics occurred in ASC+GF-releasing PAM rats which by contrast were more vulnerable to VAs. Thus, PAMs may improve cell/GF-based cardiac regeneration although caution should be paid on the electrophysiological impact of their physical interaction with the myocardium.

  1. Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase.

    Science.gov (United States)

    Wu, Mingyi; Wen, Dandan; Gao, Na; Xiao, Chuang; Yang, Lian; Xu, Li; Lian, Wu; Peng, Wenlie; Jiang, Jianmin; Zhao, Jinhua

    2015-03-06

    Fucosylated chondroitin sulfate (FCS), a structurally unusual glycosaminoglycan, has distinct anticoagulant properties, and is an especially strong inhibitor of the intrinsic factor Xase (anti-Xase). To obtain a highly selective inhibitor of human Xase, we purified six native FCSs with various sulfation patterns, prepared a series of FCS derivatives, and then elucidated the relationship between the structures and the anticoagulant activities of FCSs. FCSs 1-3 containing higher Fuc2S4S exhibit stronger AT-dependent anti-IIa activities, whereas 4-6 containing more Fuc3S4S produce potent HCII-dependent anti-IIa activities. Saccharides containing a minimum of 6-8 trisaccharide units, free carboxyl groups, and full fucosylation of GlcA may be required for potent anti-Xase activity, and approximately six trisaccharide units and partial fucosylation of GlcA may contribute to potent HCII-dependent activity. Decreasing of the molecular weights markedly reduces their AT-dependent anti-IIa activities, and even eliminates human platelet and factor XII activation. Furthermore, in vitro and in vivo studies suggested that fractions of 6-12 kDa may be very promising compounds as putative selective intrinsic Xase inhibitors with antithrombotic action, but without the consequences of major bleeding and factor XII activation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Differences in N-glycosylation of recombinant human coagulation factor VII derived from BHK, CHO, and HEK293 cells.

    Science.gov (United States)

    Böhm, Ernst; Seyfried, Birgit K; Dockal, Michael; Graninger, Michael; Hasslacher, Meinhard; Neurath, Marianne; Konetschny, Christian; Matthiessen, Peter; Mitterer, Artur; Scheiflinger, Friedrich

    2015-09-18

    BACKGROUND & Recombinant factor VII (rFVII), the precursor molecule for recombinant activated FVII (rFVIIa), is, due to its need for complex post translational modifications, produced in mammalian cells. To evaluate the suitability of a human cell line in order to produce rFVII with post-translational modifications as close as possible to pdFVII, we compared the biochemical properties of rFVII synthesized in human embryonic kidney-derived (HEK)293 cells (HEK293rFVII) with those of rFVII expressed in Chinese hamster ovary (CHO, CHOrFVII) and baby hamster kidney (BHK, BHKrFVII) cells, and also with those of plasma derived FVII (pdFVII), using various analytical methods. rFVII was purified from selected production clones derived from BHK, CHO, and HEK293 cells after stable transfection, and rFVII isolates were analyzed for protein activity, impurities and post-translational modifications. RESULTS & The analytical results showed no apparent gross differences between the various FVII proteins, except in their N-linked glycosylation pattern. Most N-glycans found on rFVII produced in HEK293 cells were not detected on rFVII from CHO and BHK cells, or, somewhat unexpectedly, on pdFVII; all other protein features were similar. HEK293rFVII glycans were mainly characterized by a higher structural variety and a lower degree of terminal sialylation, and a high amount of terminal N-acetyl galactosamines (GalNAc). All HEK293rFVII oligosaccharides contained one or more fucoses (Fuc), as well as hybrid and high mannose (Man) structures. From all rFVII isolates investigated, CHOrFVII contained the highest degree of sialylation and no terminal GalNAc, and CHO cells were therefore assumed to be the best option for the production of rFVII.

  3. Brain derived neurotrophic factor contributes to the cardiogenic potential of adult resident progenitor cells in failing murine heart.

    Directory of Open Access Journals (Sweden)

    Rasmita Samal

    Full Text Available Resident cardiac progenitor cells show homing properties when injected into the injured but not to the healthy myocardium. The molecular background behind this difference in behavior needs to be studied to elucidate how adult progenitor cells can restore cardiac function of the damaged myocardium. Since the brain derived neurotrophic factor (BDNF moderates cardioprotection in injured hearts, we focused on delineating its regulatory role in the damaged myocardium.Comparative gene expression profiling of freshly isolated undifferentiated Sca-1 progenitor cells derived either from heart failure transgenic αMHC-CyclinT1/Gαq overexpressing mice or wildtype littermates revealed transcriptional variations. Bdnf expression was up regulated 5-fold during heart failure which was verified by qRT-PCR and confirmed at protein level. The migratory capacity of Sca-1 cells from transgenic hearts was improved by 15% in the presence of 25 ng/ml BDNF. Furthermore, BDNF-mediated effects on Sca-1 cells were studied via pulsed Stable Isotope Labeling of Amino acids in Cell Culture (pSILAC proteomics approach. After BDNF treatment significant differences between newly synthesized proteins in Sca-1 cells from control and transgenic hearts were observed for CDK1, SRRT, HDGF, and MAP2K3 which are known to regulate cell cycle, survival and differentiation. Moreover BDNF repressed the proliferation of Sca-1 cells from transgenic hearts.Comparative profiling of resident Sca-1 cells revealed elevated BDNF levels in the failing heart. Exogenous BDNF (i stimulated migration, which might improve the homing ability of Sca-1 cells derived from the failing heart and (ii repressed the cell cycle progression suggesting its potency to ameliorate heart failure.

  4. Osteocyte-derived insulin-like growth factor I is not essential for the bone repletion response in mice.

    Directory of Open Access Journals (Sweden)

    Kin-Hing William Lau

    Full Text Available The present study sought to evaluate the functional role of osteocyte-derived IGF-I in the bone repletion process by determining whether deficient expression of Igf1 in osteocytes would impair the bone repletion response to one week of dietary calcium repletion after two weeks of dietary calcium deprivation. As expected, the two-week dietary calcium depletion led to hypocalcemia, secondary hyperparathyroidism, and increases in bone resorption and bone loss in both Igf1 osteocyte conditional knockout (cKO mutants and WT control mice. Thus, conditional disruption of Igf1 in osteocytes did not impair the calcium depletion-induced bone resorption. After one week of calcium repletion, both cKO mutants and WT littermates showed an increase in endosteal bone formation attended by the reduction in osteoclast number, indicating that deficient Igf1 expression in osteocytes also did not have deleterious effects on the bone repletion response. The lack of an effect of deficient osteocyte-derived IGF-I expression on bone repletion is unexpected since previous studies show that these Igf1 osteocyte cKO mice exhibited impaired developmental growth and displayed complete resistance to bone anabolic effects of loading. These studies suggest that there is a dichotomy between the mechanisms necessary for anabolic responses to mechanical loading and the regulatory hormonal and anabolic skeletal repletion following low dietary calcium challenge. In conclusion, to our knowledge this study has demonstrated for the first time that osteocyte-derived IGF-I, which is essential for anabolic bone response to mechanical loading, is not a key regulatory factor for bone repletion after a low calcium challenge.

  5. Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells.

    Science.gov (United States)

    Mellado-López, Maravillas; Griffeth, Richard J; Meseguer-Ripolles, Jose; Cugat, Ramón; García, Montserrat; Moreno-Manzano, Victoria

    2017-01-01

    Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100  μ M of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

  6. Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Maravillas Mellado-López

    2017-01-01

    Full Text Available Adipose-derived stem cells (ASCs are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100 μM of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

  7. A Tumor Suppressor Gene Product, Platelet-Derived Growth Factor Receptor-Like Protein Controls Chondrocyte Proliferation and Differentiation.

    Science.gov (United States)

    Kawata, Kazumi; Kubota, Satoshi; Eguchi, Takanori; Aoyama, Eriko; Moritani, Norifumi H; Oka, Morihiko; Kawaki, Harumi; Takigawa, Masaharu

    2017-11-01

    The platelet-derived growth factor receptor-like (PDGFRL) gene is regarded as a tumor suppressor gene. However, nothing is known about the molecular function of PDGFRL. In this study, we initially clarified its function in chondrocytes. Among all cell lines examined, the PDGFRL mRNA level was the highest in chondrocytic HCS-2/8 cells. Interestingly, the proliferation of chondrocytic HCS-2/8 cells was promoted by PDGFRL overexpression, whereas that of the breast cancer-derived MDA-MB-231 cells was inhibited. Of note, in PDGFRL-overexpressing HCS-2/8 cells, the expression of chondrocyte differentiation marker genes, SOX9, ACAN, COL2A1, COL10A1, and ALP, was decreased. Moreover, we confirmed the expression of PDGFRL mRNA in normal cartilage tissue and chondrocytes. Eventually, the expression of PDGFRL mRNA in condrocytes except in the case of hypertrophic chondrocytes was demonstrated in vivo and in vitro. These findings suggest that PDGFRL plays the different roles, depending upon cell types. Particularly, in chondrocytes, PDGFRL may play a new and important role which is distinct from the function previously reported. J. Cell. Biochem. 118: 4033-4044, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Cloning, purification and structure determination of the HIV integrase-binding domain of lens epithelium-derived growth factor.

    Science.gov (United States)

    Hannon, Clare; Cruz-Migoni, Abimael; Platonova, Olga; Owen, Robin L; Nettleship, Joanne E; Miller, Ami; Carr, Stephen B; Harris, Gemma; Rabbitts, Terence H; Phillips, Simon E V

    2018-03-01

    Lens epithelium-derived growth factor (LEDGF)/p75 is the dominant binding partner of HIV-1 integrase in human cells. The crystal structure of the HIV integrase-binding domain (IBD) of LEDGF has been determined in the absence of ligand. IBD was overexpressed in Escherichia coli, purified and crystallized by sitting-drop vapour diffusion. X-ray diffraction data were collected at Diamond Light Source to a resolution of 2.05 Å. The crystals belonged to space group P2 1 , with eight polypeptide chains in the asymmetric unit arranged as an unusual octamer composed of four domain-swapped IBD dimers. IBD exists as a mixture of monomers and dimers in concentrated solutions, but the dimers are unlikely to be biologically relevant.

  9. Brain derived neurotrophic factor mediated learning, fear acquisition and extinction as targets for developing novel treatments for anxiety

    Directory of Open Access Journals (Sweden)

    Karina Soares de Oliveira

    Full Text Available ABSTRACT Anxiety and obsessive-compulsive related disorders are highly prevalent and disabling disorders for which there are still treatment gaps to be explored. Fear is a core symptom of these disorders and its learning is highly dependent on the activity of the neurotrophin brain-derived neurotrophic factor (BDNF. Should BDNF-mediated fear learning be considered a target for the development of novel treatments for anxiety and obsessive-compulsive related disorders? We review the evidence that suggests that BDNF expression is necessary for the acquisition of conditioned fear, as well as for the recall of its extinction. We describe the findings related to fear learning and genetic/epigenetic manipulation of Bdnf expression in animals and BDNF allelic variants in humans. Later, we discuss how manipulation of BDNF levels represents a promising potential treatment target that may increase the benefits of therapies that extinguish previously conditioned fear.

  10. Antidiabetic Effect of Brain-Derived Neurotrophic Factor and Its Association with Inflammation in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Ceren Eyileten

    2017-01-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is a neurotrophin, which plays an important role in the central nervous system, and systemic or peripheral inflammatory conditions, such as acute coronary syndrome and type 2 diabetes mellitus (T2DM. BDNF is also expressed in several nonneuronal tissues, and platelets are the major source of peripheral BDNF. Here, we reviewed the potential role of BDNF in platelet reactivity in T2DM and its association with selected inflammatory and platelet activation mediators. Besides that, we focused on adipocytokines such as leptin, resistin, and adiponectin which are considered to take part in inflammation and both lipid and glucose metabolism in diabetic patients as previous studies showed the relation between adipocytokines and BDNF. We also reviewed the evidences of the antidiabetic effect of BDNF and the association with circulating inflammatory cytokines in T2DM.

  11. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Ericksen Mielle Borba

    2016-12-01

    Full Text Available Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD pathology. Serum brain-derived neurotrophic factor (BDNF reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]. Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results: MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion: The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  12. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease.

    Science.gov (United States)

    Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, Márcia Lorena Fagundes

    2016-01-01

    Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  13. Cross-sectional associations of objectively measured physical activity with brain-derived neurotrophic factor in adolescents

    DEFF Research Database (Denmark)

    Huang, Tao; Gejl, Anne Kær; Tarp, Jakob

    2017-01-01

    .035). In girls, mean physical activity and MVPA were not associated with serum BDNF. Without adjustment for wear time, sedentary time was not associated with serum BDNF in either sex. CONCLUSION: These findings indicate that higher physical activity is associated with lower serum BDNF in boys, but not in girls....... standardized procedures. RESULTS: With adjustment for age, pubertal status and body mass index, mean physical activity (counts per minute) was negatively associated with serum BDNF in boys (P=0.013). Similarly, moderate-to-vigorous physical activity (MVPA) was negatively associated with serum BDNF in boys (P=0......OBJECTIVE: The purpose of this study was to examine the associations between objectively measured physical activity and serum brain-derived neurotrophic factor (BDNF) in adolescents. METHODS: Cross-sectional analyses were performed using data from 415 adolescents who participated in the 2015 follow...

  14. Use of multitarget tyrosine kinase inhibitors to attenuate platelet-derived growth factor signalling in lung disease

    Directory of Open Access Journals (Sweden)

    Rana Kanaan

    2017-10-01

    Full Text Available Platelet-derived growth factors (PDGFs and their receptors (PDGFRs play a fundamental role in the embryonic development of the lung. Aberrant PDGF signalling has been documented convincingly in a large variety of pulmonary diseases, including idiopathic pulmonary arterial hypertension, lung cancer and lung fibrosis. Targeting PDGF signalling has been proven to be effective in these diseases. In clinical practice, the most effective way to block PDGF signalling is to inhibit the activity of the intracellular PDGFR kinases. Although the mechanism of action of such drugs is not specific for PDGF signalling, the medications have a broad therapeutic index that allows clinical use. The safety profile and therapeutic opportunities of these and future medications that target PDGFs and PDGFRs are reviewed.

  15. Plasma glial cell line-derived neurotrophic factor in patients with major depressive disorder: a preliminary study.

    Science.gov (United States)

    Lee, Bun-Hee; Hong, Jin-Pyo; Hwang, Jung-A; Na, Kyoung-Sae; Kim, Won-Joong; Trigo, Jose; Kim, Yong-Ku

    2016-02-01

    Some clinical studies have reported reduced peripheral glial cell line-derived neurotrophic factor (GDNF) level in elderly patients with major depressive disorder (MDD). We verified whether a reduction in plasma GDNF level was associated with MDD. Plasma GDNF level was measured in 23 healthy control subjects and 23 MDD patients before and after 6 weeks of treatment. Plasma GDNF level in MDD patients at baseline did not differ from that in healthy controls. Plasma GDNF in MDD patients did not differ significantly from baseline to the end of treatment. GDNF level was significantly lower in recurrent-episode MDD patients than in first-episode patients before and after treatment. Our findings revealed significantly lower plasma GDNF level in recurrent-episode MDD patients, although plasma GDNF levels in MDD patients and healthy controls did not differ significantly. The discrepancy between our study and previous studies might arise from differences in the recurrence of depression or the ages of the MDD patients.

  16. Bacteria-induced release of white cell--and platelet-derived vascular endothelial growth factor in vitro

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Werther, K; Mynster, T

    2001-01-01

    BACKGROUND AND OBJECTIVES: Poor prognosis after resection of primary colorectal cancer may be related to the combination of perioperative blood transfusion and subsequent development of infectious complications. White blood cell--and platelet-derived cancer growth substances, including vascular...... endothelial growth factor (VEGF), may be involved in this process. Therefore, we studied the in vitro release of VEGF from white blood cells and platelets stimulated by bacterial antigens and supernatants from stored red cell components. MATERIALS AND METHODS: Eight units of whole blood (WB) and eight units...... of buffy-coat-depleted red cell (SAGM) blood were donated by healthy blood donors. Subsequently, half of every unit was leucocyte depleted by filtration, and all 32 half-units were stored under standard conditions for 35 days. Just after storage, and on days 7, 21 and 35 during storage, aliquots...

  17. Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

    Science.gov (United States)

    Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

    2012-01-01

    Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

  18. The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents: The CHAMPS-study DK.

    Science.gov (United States)

    Pedersen, Natascha Holbæk; Tarp, Jakob; Andersen, Lars Bo; Gejl, Anne Kær; Huang, Tao; Peijs, Lone; Bugge, Anna

    2017-01-01

    Cardiovascular disease and type 2 diabetes pose a global health burden. Therefore, clarifying the pathology of these risk factors is essential. Previous studies have found positive and negative associations between one or more cardiovascular risk factors and brain-derived neurotrophic factor (BDNF) probably due to diverse methodological approaches when analysing peripheral BDNF levels. Moreover, only a few studies have been performed in youth populations. Consequently, the main objective of this study was to examine the association between serum BDNF and a composite z-score consisting of six cardiovascular risk factors. A secondary aim was to examine the associations between serum BDNF and each of the six risk factors. Four hundred and forty-seven apparently healthy adolescents between 11-17 years of age participated in this cross-sectional study. Cardiorespiratory fitness (CRF), anthropometrics, pubertal status, blood pressure (BP), serum BDNF, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), blood glucose and insulin were measured. Information about alcohol consumption and socio-economic status was collected via questionnaires. Associations were modelled using linear regression analysis. Serum BDNF was positively associated with the composite z-score in the total study sample (standardized beta coefficient (std.β) = 0.10, P = 0.037). In males, serum BDNF was positively associated with the composite z-score (Std. β = 0.14, P = 0.034) and HOMA-IR (Std. β = 0.19, P = 0.004), and negatively associated with CRF (Std. β = -0.15, P = 0.026). In females, BDNF was positively associated with TG (Std. β = 0.14, P = 0.030) and negatively associated with waist circumference (WC) (Std. β = -0.16, P = 0.012). Serum BDNF was positively associated with a composite z-score of cardiovascular risk factors. This association seems to be mainly driven by the association between TG, HOMA-IR and serum BDNF, and particularly for males. Further longitudinal research

  19. The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents: The CHAMPS-study DK.

    Directory of Open Access Journals (Sweden)

    Natascha Holbæk Pedersen

    Full Text Available Cardiovascular disease and type 2 diabetes pose a global health burden. Therefore, clarifying the pathology of these risk factors is essential. Previous studies have found positive and negative associations between one or more cardiovascular risk factors and brain-derived neurotrophic factor (BDNF probably due to diverse methodological approaches when analysing peripheral BDNF levels. Moreover, only a few studies have been performed in youth populations. Consequently, the main objective of this study was to examine the association between serum BDNF and a composite z-score consisting of six cardiovascular risk factors. A secondary aim was to examine the associations between serum BDNF and each of the six risk factors.Four hundred and forty-seven apparently healthy adolescents between 11-17 years of age participated in this cross-sectional study. Cardiorespiratory fitness (CRF, anthropometrics, pubertal status, blood pressure (BP, serum BDNF, high-density lipoprotein cholesterol (HDL-C, triglyceride (TG, blood glucose and insulin were measured. Information about alcohol consumption and socio-economic status was collected via questionnaires. Associations were modelled using linear regression analysis.Serum BDNF was positively associated with the composite z-score in the total study sample (standardized beta coefficient (std.β = 0.10, P = 0.037. In males, serum BDNF was positively associated with the composite z-score (Std. β = 0.14, P = 0.034 and HOMA-IR (Std. β = 0.19, P = 0.004, and negatively associated with CRF (Std. β = -0.15, P = 0.026. In females, BDNF was positively associated with TG (Std. β = 0.14, P = 0.030 and negatively associated with waist circumference (WC (Std. β = -0.16, P = 0.012.Serum BDNF was positively associated with a composite z-score of cardiovascular risk factors. This association seems to be mainly driven by the association between TG, HOMA-IR and serum BDNF, and particularly for males. Further longitudinal

  20. Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons.

    Science.gov (United States)

    Noble, Emily E; Mavanji, Vijayakumar; Little, Morgan R; Billington, Charles J; Kotz, Catherine M; Wang, ChuanFeng

    2014-10-01

    Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for 7 weeks of exercise intervention. Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (pdiet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. Published by Elsevier Inc.

  1. Transport methods: general. 6. A Flux-Limited Diffusion Theory Derived from the Maximum Entropy Eddington Factor

    International Nuclear Information System (INIS)

    Yin, Chukai; Su, Bingjing

    2001-01-01

    The Minerbo's maximum entropy Eddington factor (MEEF) method was proposed as a low-order approximation to transport theory, in which the first two moment equations are closed for the scalar flux f and the current F through a statistically derived nonlinear Eddington factor f. This closure has the ability to handle various degrees of anisotropy of angular flux and is well justified both numerically and theoretically. Thus, a lot of efforts have been made to use this approximation in transport computations, especially in the radiative transfer and astrophysics communities. However, the method suffers numerical instability and may lead to anomalous solutions if the equations are solved by certain commonly used (implicit) mesh schemes. Studies on numerical stability in one-dimensional cases show that the MEEF equations can be solved satisfactorily by an implicit scheme (of treating δΦ/δx) if the angular flux is not too anisotropic so that f 32 , the classic diffusion solution P 1 , the MEEF solution f M obtained by Riemann solvers, and the NFLD solution D M for the two problems, respectively. In Fig. 1, NFLD and MEEF quantitatively predict very close results. However, the NFLD solution is qualitatively better because it is continuous while MEEF predicts unphysical jumps near the middle of the slab. In Fig. 2, the NFLD and MEEF solutions are almost identical, except near the material interface. In summary, the flux-limited diffusion theory derived from the MEEF description is quantitatively as accurate as the MEEF method. However, it is more qualitatively correct and user-friendly than the MEEF method and can be applied efficiently to various steady-state problems. Numerical tests show that this method is widely valid and overall predicts better results than other low-order approximations for various kinds of problems, including eigenvalue problems. Thus, it is an appealing approximate solution technique that is fast computationally and yet is accurate enough for a

  2. Association study of a brain-derived neurotrophic factor polymorphism and short-term antidepressant response in major depressive disorders

    Directory of Open Access Journals (Sweden)

    Lung-Cheng Huang

    2008-10-01

    Full Text Available Eugene Lin1,7, Po See Chen2,6,7, Lung-Cheng Huang3,4, Sen-Yen Hsu51Vita Genomics, Inc., Wugu Shiang, Taipei, Taiwan; 2Department of Psychiatry, Hospital and College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Psychiatry, National Taiwan University Hospital Yun-Lin Branch, Taiwan; 4Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Psychiatry, Chi Mei Medical Center, Liouying, Tainan, Taiwan; 6Department of Psychiatry, National Cheng Kung University Hospital, Dou-liou Branch, Yunlin, Taiwan; 7These authors contributed equally to this workAbstract: Major depressive disorder (MDD is one of the most common mental disorders worldwide. Single nucleotide polymorphisms (SNPs can be used in clinical association studies to determine the contribution of genes to drug efficacy. A common SNP in the brain-derived neurotrophic factor (BDNF gene, a methionine (Met substitution for valine (Val at codon 66 (Val66Met, is a candidate SNP for influencing antidepressant treatment outcome. In this study, our goal was to determine the relationship between the Val66Met polymorphism in the BDNF gene and the rapid antidepressant response to venlafaxine in a Taiwanese population with MDD. Overall, the BDNF Val66Met polymorphism was found not to be associated with short-term venlafaxine treatment outcome. However, the BDNF Val66Met polymorphism showed a trend to be associated with rapid venlafaxine treatment response in female patients. Future research with independent replication in large sample sizes is needed to confirm the role of the BDNF Val66Met polymorphism identified in this study.Keywords: antidepressant response, brain-derived neurotrophic factor, major depressive disorder, serotonin and norepinephrine reuptake inhibitor, single nucleotide polymorphisms

  3. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy

    Science.gov (United States)

    Askari, Arman T.; Unzek, Samuel; Popovic, Zoran B.; Goldman, Corey K.; Forudi, Farhad; Kiedrowski, Matthew; Rovner, Aleksandr; Ellis, Stephen G.; Thomas, James D.; DiCorleto, Paul E.; hide

    2003-01-01

    BACKGROUND: Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy. METHODS: We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells. Shortening fraction and myocardial strain by tissue doppler imaging were quantified by echocardiography. FINDINGS: Stem-cell mobilisation with filgrastim alone did not lead to engraftment of bone-marrow-derived cells. Stromal-cell-derived factor 1 (SDF-1), required for stem-cell homing to bone marrow, was upregulated immediately after myocardial infarction and downregulated within 7 days. 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control vs SDF-1-expressing cardiac fibroblasts mean 7.2 [SD 3.4] vs 33.2 [6.0] cells/mm2, n=4 per group, pcell homing to injured myocardium and suggest a strategy for directed stem-cell engraftment into injured tissues. Our findings also indicate that therapeutic strategies focused on stem-cell mobilisation for regeneration of myocardial tissue must be initiated within days of myocardial infarction unless signalling for stem-cell homing is re-established.

  4. Growth inhibition of thyroid follicular cell-derived cancers by the opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis

    International Nuclear Information System (INIS)

    McLaughlin, Patricia J; Zagon, Ian S; Park, Sunny S; Conway, Andrea; Donahue, Renee N; Goldenberg, David

    2009-01-01

    Carcinoma of the thyroid gland is an uncommon cancer, but the most frequent malignancy of the endocrine system. Most thyroid cancers are derived from the follicular cell. Follicular carcinoma (FTC) is considered more malignant than papillary thyroid carcinoma (PTC), and anaplastic thyroid cancer (ATC) is one of the most lethal human cancers. Opioid Growth Factor (OGF; chemical term - [Met 5 ]-enkephalin) and its receptor, OGFr, form an inhibitory axis regulating cell proliferation. Both the peptide and receptor have been detected in a wide variety of cancers, and OGF is currently used clinically as a biotherapy for some non-thyroid neoplasias. This study addressed the question of whether the OGF-OGFr axis is present and functional in human thyroid follicular cell - derived cancer. Utilizing human ATC (KAT-18), PTC (KTC-1), and FTC (WRO 82-1) cell lines, immunohistochemistry was employed to ascertain the presence and location of OGF and OGFr. The growth characteristics in the presence of OGF or the opioid antagonist naltrexone (NTX), and the specificity of opioid peptides for proliferation of ATC, were established in KAT-18 cells. Dependence on peptide and receptor were investigated using neutralization studies with antibodies and siRNA experiments, respectively. The mechanism of peptide action on DNA synthesis and cell survival was ascertained. The ubiquity of the OGF-OGFr axis in thyroid follicular cell-derived cancer was assessed in KTC-1 (PTC) and WRO 82-1 (FTC) tumor cells. OGF and OGFr were present in KAT-18 cells. Concentrations of 10 -6 M OGF inhibited cell replication up to 30%, whereas NTX increased cell growth up to 35% relative to cultures treated with sterile water. OGF treatment reduced cell number by as much as 38% in KAT-18 ATC in a dose-dependent and receptor-mediated manner. OGF antibodies neutralized the inhibitory effects of OGF, and siRNA knockdown of OGFr negated growth inhibition by OGF. Cell survival was not altered by OGF, but DNA synthesis

  5. The proangiogenic phenotype of tumor-derived endothelial cells is reverted by the overexpression of platelet-activating factor acetylhydrolase.

    Science.gov (United States)

    Doublier, Sophie; Ceretto, Monica; Lupia, Enrico; Bravo, Stefania; Bussolati, Benedetta; Camussi, Giovanni

    2007-10-01

    We previously reported that human tumor-derived endothelial cells (TEC) have an angiogenic phenotype related to the autocrine production of several angiogenic factors. The purpose of the present study was to evaluate whether an enhanced synthesis of platelet-activating factor (PAF) might contribute to the proangiogenic characteristics of TEC and whether its inactivation might inhibit angiogenesis. To address the potential role of PAF in the proangiogenic characteristics of TEC, we engineered TEC to stably overexpress human plasma PAF-acetylhydrolase (PAF-AH), the major PAF-inactivating enzyme, and we evaluated in vitro and in vivo angiogenesis. TECs were able to synthesize a significantly enhanced amount of PAF compared with normal human microvascular endothelial cells when stimulated with thrombin, vascular endothelial growth factor, or soluble CD154. Transfection of TEC with PAF-AH (TEC-PAF-AH) significantly inhibited apoptosis resistance and spontaneous motility of TEC. In addition, PAF and vascular endothelial growth factor stimulation enhanced the motility and adhesion of TEC but not of TEC-PAF-AH. In vitro, TEC-PAF-AH lost the characteristic ability of TEC to form vessel-like structures when plated on Matrigel. Finally, when cells were injected s.c. within Matrigel in severe combined immunodeficiency mice or coimplanted with a renal carcinoma cell line, the overexpression of PAF-AH induced a significant reduction of functional vessel formation. These results suggest that inactivation of PAF, produced by TEC, by the overexpression of plasma PAF-AH affects survival, migration, and the angiogenic response of TEC both in vitro and in vivo.

  6. Brain-derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress.

    Science.gov (United States)

    Dretsch, Michael N; Williams, Kathy; Emmerich, Tanja; Crynen, Gogce; Ait-Ghezala, Ghania; Chaytow, Helena; Mathura, Venkat; Crawford, Fiona C; Iverson, Grant L

    2016-01-01

    In addition to experiencing traumatic events while deployed in a combat environment, there are other factors that contribute to the development of posttraumatic stress disorder (PTSD) in military service members. This study explored the contribution of genetics, childhood environment, prior trauma, psychological, cognitive, and deployment factors to the development of traumatic stress following deployment. Both pre- and postdeployment data on 231 of 458 soldiers were analyzed. Postdeployment assessments occurred within 30 days from returning stateside and included a battery of psychological health, medical history, and demographic questionnaires; neurocognitive tests; and blood serum for the D2 dopamine receptor (DRD2), apolipoprotein E (APOE), and brain-derived neurotropic factor (BDNF) genes. Soldiers who screened positive for traumatic stress at postdeployment had significantly higher scores in depression (d = 1.91), anxiety (d = 1.61), poor sleep quality (d = 0.92), postconcussion symptoms (d = 2.21), alcohol use (d = 0.63), traumatic life events (d = 0.42), and combat exposure (d = 0.91). BDNF Val66 Met genotype was significantly associated with risk for sustaining a mild traumatic brain injury (mTBI) and screening positive for traumatic stress. Predeployment traumatic stress, greater combat exposure and sustaining an mTBI while deployed, and the BDNF Met/Met genotype accounted for 22% of the variance of postdeployment PTSD scores (R (2)  = 0.22, P PTSD scores. These findings suggest predeployment traumatic stress, genetic, and environmental factors have unique contributions to the development of combat-related traumatic stress in military service members.

  7. Pigment epithelium-derived factor, insulin sensitivity, and adiposity in polycystic ovary syndrome: impact of exercise training.

    Science.gov (United States)

    Joham, Anju E; Teede, Helena J; Hutchison, Samantha K; Stepto, Nigel K; Harrison, Cheryce L; Strauss, Boyd J; Paul, Eldho; Watt, Matthew J

    2012-12-01

    Pigment epithelium-derived factor (PEDF) is upregulated in obese rodents and is involved in the development of insulin resistance (IR). We aim to explore the relationships between PEDF, adiposity, insulin sensitivity, and cardiovascular risk factors in obese women with polycystic ovary syndrome (PCOS) and weight-matched controls and to examine the impact of endurance exercise training on PEDF. This prospective cohort intervention study was based at a tertiary medical center. Twenty obese PCOS women and 14 non-PCOS weight-matched women were studied at baseline. PEDF, cardiometabolic markers, detailed body composition, and euglycemic-hyperinsulinemic clamps were performed and measures were repeated in 10 PCOS and 8 non-PCOS women following 12 weeks of intensified aerobic exercise. Mean glucose infusion rate (GIR) was 31.7% lower (P = 0.02) in PCOS compared to controls (175.6 ± 96.3 and 257.2 ± 64.3 mg.m(-2).min(-1)) at baseline, yet both PEDF and BMI were similar between groups. PEDF negatively correlated to GIR (r = -0.41, P = 0.03) and high-density lipoprotein (HDL) (r = -0.46, P = 0.01), and positively to cardiovascular risk factors, systolic (r = 0.41, P = 0.02) and diastolic blood pressure (r = 0.47, P = 0.01) and triglycerides (r = 0.49, P = 0.004). The correlation with GIR was not significant after adjusting for fat mass (P = 0.07). Exercise training maintained BMI and increased GIR in both groups; however, plasma PEDF was unchanged. In summary, PEDF is not elevated in PCOS, is not associated with IR when adjusted for fat mass, and is not reduced by endurance exercise training despite improved insulin sensitivity. PEDF was associated with cardiovascular risk factors, suggesting PEDF may be a marker of cardiovascular risk status.

  8. Comparison of Brain-Derived Neurotrophic Factor (BDNF and Insulin-like Growth Factor 1 (IGF-1 Responses to Different Endurance Training Intensities in Runner Men

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    M. Habibian

    2017-04-01

    Full Text Available Aims: Blood neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF and Insulin-like Growth Factor 1 (IGF-1, mediate exercise- induced health benefits in humans. The purpose of this study was to compare the response of BDNF and IGF-1 to different endurance training intensities in runner men. Materials & Methods: In this semi-experimental study with pre-test-posttest design in 2015, 10 people of male runners from Gorgan were selected through purposeful and accessible sampling. The endurance training protocol was 6 km running with moderate (70-75% of heart rate reserve or severe (80-85% of heart rate reserve intensity, which was performed within a week's interval. Fasting blood samples were collected before and immediately after both acute training sessions and serum levels of BDNF and IGF-1 were measured by ELISA and radioimmunoassay enzyme. Data were analyzed by SPSS 20 software using independent t-test and paired t-test. Findings: Both acute endurance training significantly increased serum levels of BDNF and IGF-1 in runners, but high intensity endurance exercises increased BDNF levels in comparison with moderate intensity (p0.05. Conclusion: Serum BDNF response in endurance athletes is affected by the intensity of exercise, so that the effect of high intensity endurance training on BDNF levels is greater than moderate intensity exercise, but the response of IGF-1 to acute endurance training is independent of the intensity of exercise.

  9. High efficiency non-viral transfection of retinal and iris pigment epithelial cells with pigment epithelium-derived factor.

    Science.gov (United States)

    Thumann, G; Stöcker, M; Maltusch, C; Salz, A K; Barth, S; Walter, P; Johnen, S

    2010-02-01

    Transplantation of pigment epithelial cells in patients with age-related macular degeneration and Parkinson's disease has the potential to improve functional rehabilitation. Genetic modification of cells before transplantation may allow the delivery of neuroprotective factors to achieve functional improvement. As transplantation of cells modified using viral vectors is complicated by the possible dissemination of viral particles and severe immune reactions, we have explored non-viral methods to insert genetic material in pigment epithelial cells. Using lipofection or nucleofection ARPE-19 cells, freshly isolated and primary retinal and iris pigment epithelial (IPE) cells were transfected with plasmids encoding green fluorescent protein (GFP) and with three plasmids encoding recombinant pigment epithelium-derived factor (PEDF) and GFP. Transfection efficiency was evaluated by fluorescence microscopy and stability of protein expression by immunoblotting. Pigment epithelial cells were successfully transfected with plasmid encoding GFP. Expression of GFP in ARPE-19 was transient, but was observed for up to 1 year in IPE cells. Analysis of pigment epithelial cells transfected with PEDF plasmids revealed that PEDF fusion proteins were successfully expressed and functionally active. In conclusion, efficient transfer of genetic information in pigment epithelial cells can be achieved using non-viral transfection protocols.

  10. β5 Integrin Up-Regulation in Brain-Derived Neurotrophic Factor Promotes Cell Motility in Human Chondrosarcoma

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    Li, Te-Mao; Fong, Yi-Chin; Liu, Shan-Chi; Chen, Po-Chun; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis; it has a poor prognosis and shows a predilection for metastasis to the lungs. Brain derived neurotrophic factor (BDNF) is a small-molecule protein from the neurotrophin family of growth factors that is associated with the disease status and outcomes of cancers. However, the effect of BDNF on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma tissues showed significant expression of BDNF, which was higher than that in normal cartilage and primary chondrocytes. We also found that BDNF increased the migration and expression of β5 integrin in human chondrosarcoma cells. In addition, knockdown of BDNF expression markedly inhibited migratory activity. BDNF-mediated migration and β5 integrin up-regulation were attenuated by antibody, inhibitor, or siRNA against the TrkB receptor. Pretreatment of chondrosarcoma cells with PI3K, Akt, and NF-κB inhibitors or mutants also abolished BDNF-promoted migration and integrin expression. The PI3K, Akt, and NF-κB signaling pathway was activated after BDNF treatment. Taken together, our results indicate that BDNF enhances the migration of chondrosarcoma by increasing β5 integrin expression through a signal transduction pathway that involves the TrkB receptor, PI3K, Akt, and NF-κB. BDNF thus represents a promising new target for treating chondrosarcoma metastasis. PMID:23874483

  11. Morphine induces expression of platelet-derived growth factor in human brain microvascular endothelial cells: implication for vascular permeability.

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    Hongxiu Wen

    Full Text Available Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Morphine, often abused by HIV-infected patients, is known to accelerate neuroinflammation associated with HIV-1 infection. Detailed molecular mechanisms of morphine action however, remain poorly understood. Platelet-derived growth factor (PDGF has been implicated in a number of pathological conditions, primarily due to its potent mitogenic and permeability effects. Whether morphine exposure results in enhanced vascular permeability in brain endothelial cells, likely via induction of PDGF, remains to be established. In the present study, we demonstrated morphine-mediated induction of PDGF-BB in human brain microvascular endothelial cells, an effect that was abrogated by the opioid receptor antagonist-naltrexone. Pharmacological blockade (cell signaling and loss-of-function (Egr-1 approaches demonstrated the role of mitogen-activated protein kinases (MAPKs, PI3K/Akt and the downstream transcription factor Egr-1 respectively, in morphine-mediated induction of PDGF-BB. Functional significance of increased PDGF-BB manifested as increased breach of the endothelial barrier as evidenced by decreased expression of the tight junction protein ZO-1 in an in vitro model system. Understanding the regulation of PDGF expression may provide insights into the development of potential therapeutic targets for intervention of morphine-mediated neuroinflammation.

  12. Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

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    Simon Turcotte

    2007-10-01

    Full Text Available Prostate-derived Ets transcription factor (PDEF has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1. Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001, moderate to good differentiation (less than grade III, P = .01, dissemination to axillary lymph nodes (P = .002. PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002. It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001. Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

  13. The detection of platelet derived growth factor using decoupling of quencher-oligonucleotide from aptamer/quantum dot bioconjugates

    International Nuclear Information System (INIS)

    Kim, Gang-Il; Sung, Yun-Mo; Kim, Kyung-Woo; Oh, Min-Kyu

    2009-01-01

    High-sensitivity, high-specificity detection of platelet derived growth factor (PDGF)-BB was realized using the change in fluorescence resonance energy transfer (FRET) occurring between quantum dot (QD) donors and black hole quencher (BHQ) acceptors. CdSe/ZnS QD/mercaptoacetic acid (MAA)/PDGF aptamer bioconjugates were successfully synthesized using ligand exchange. Black hole quencher (BHQ)-bearing oligonucleotide molecules showing partial sequence matching to PDGF aptamer were attached to PDGF aptamers and photoluminescence (PL) quenching was obtained through FRET. By adding target PDGF-BB to the bioconjugates containing BHQs, PL recovery was detected due to detachment of BHQ-bearing oligonucleotide from the PDGF aptamer as a result of the difference in affinity to the PDGF aptamer. The detection limit of the sensor was ∼0.4 nM and the linearity was maintained up to 1.6 nM in the PL intensity versus concentration curve. Measurement of PL recovery was suggested as a strong tool for high-sensitivity detection of PDGF-BB. Epidermal growth factor (EGF), the negative control molecule, did not contribute to PL recovery due to lack of binding affinity to the PDGF aptamers, which demonstrates the selectivity of the biosensor.

  14. Role of Nuclear Factor (Erythroid-Derived 2-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells

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    Anna Hammer

    2017-12-01

    Full Text Available To date, the intracellular signaling pathways involved in dendritic cell (DC function are poorly understood. The antioxidative transcription factor nuclear factor (erythroid-derived 2-like 2 (Nrf2 has been shown to affect maturation, function, and subsequent DC-mediated T cell responses of murine and human DCs. In experimental autoimmune encephalomyelitis (EAE, as prototype animal model for a T helper cell-mediated autoimmune disease, antigen presentation, cytokine production, and costimulation by DCs play a major role. We explore the role of Nrf2 in DC function, and DC-mediated T cell responses during T cell-mediated autoimmunity of the central nervous system using genetic ablation and pharmacological activation in mice and men to corroborate our data in a translational setting. In murine and human DCs, monomethyl fumarate induced Nrf2 signaling inhibits DC maturation and DC-mediated T cell proliferation by reducing inflammatory cytokine production and expression of costimulatory molecules. In contrast, Nrf2-deficient DCs generate more activated T helper cells (Th1/Th17 but fewer regulatory T cells and foster T cell proliferation. Transfer of DCs with Nrf2 activation during active EAE reduces disease severity and T cell infiltration. Our data demonstrate that Nrf2 signaling modulates autoimmunity in murine and human systems via inhibiting DC maturation and function thus shedding further light on the mechanism of action of antioxidative stress pathways in antigen-presenting cells.

  15. Brain derived neurotrophic factor gene (BDNF) and personality traits: the modifying effect of season of birth and sex.

    Science.gov (United States)

    Kazantseva, A; Gaysina, D; Kutlumbetova, Yu; Kanzafarova, R; Malykh, S; Lobaskova, M; Khusnutdinova, E

    2015-01-02

    Personality traits are complex phenotypes influenced by interactions of multiple genetic variants of small effect and environmental factors. It has been suggested that the brain derived neurotrophic factor gene (BDNF) is involved in personality traits. Season of birth (SOB) has also been shown to affect personality traits due to its influences on brain development during prenatal and early postnatal periods. The present study aimed to investigate the effects of BDNF on personality traits; and the modifying effects of SOB and sex on associations between BDNF and personality traits. A sample of 1018 young adults (68% women; age range 17-25years) of Caucasian origin from the Russian Federation was assessed on personality traits (Novelty Seeking, Harm Avoidance, Reward Dependence, Persistence, Self-directedness, Cooperativeness, Self-transcendence) with the Temperament and Character Inventory-125 (TCI-125). Associations between personality traits and 12 BDNF SNPs were tested using linear regression models. The present study demonstrated the effect of rs11030102 on Persistence in females only (PFDR=0.043; r(2)=1.3%). There were significant interaction effects between Val66Met (rs6265) and SOB (PFDR=0.048, r(2)=1.4%), and between rs2030323 and SOB (PFDR=0.042, r(2)=1.3%), on Harm Avoidance. Our findings provide evidence for the modifying effect of SOB on the association between BDNF and Harm Avoidance, and for the modifying effect of sex on the association between BDNF and Persistence. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression.

    Science.gov (United States)

    Ignácio, Z M; Réus, G Z; Abelaira, H M; Quevedo, J

    2014-09-05

    Epidemiological studies have shown significant results in the interaction between the functions of brain-derived neurotrophic factor (BDNF) and 5-HT in mood disorders, such as major depressive disorder (MDD). The latest research has provided convincing evidence that gene transcription of these molecules is a target for epigenetic changes, triggered by stressful stimuli that starts in early childhood and continues throughout life, which are subsequently translated into structural and functional phenotypes culminating in depressive disorders. The short variants of 5-HTTLPR and BDNF-Met are seen as forms which are predisposed to epigenetic aberrations, which leads individuals to a susceptibility to environmental adversities, especially when subjected to stress in early life. Moreover, the polymorphic variants also feature epistatic interactions in directing the functional mechanisms elicited by stress and underlying the onset of depressive disorders. Also emphasized are works which show some mediators between stress and epigenetic changes of the 5-HTT and BDNF genes, such as the hypothalamic-pituitary-adrenal (HPA) axis and the cAMP response element-binding protein (CREB), which is a cellular transcription factor. Both the HPA axis and CREB are also involved in epistatic interactions between polymorphic variants of 5-HTTLPR and Val66Met. This review highlights some research studying changes in the epigenetic patterns intrinsic to genes of 5-HTT and BDNF, which are related to lifelong environmental adversities, which in turn increases the risks of developing MDD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Moderate-intensity interval training increases serum brain-derived neurotrophic factor level and decreases inflammation in Parkinson's disease patients.

    Science.gov (United States)

    Zoladz, J A; Majerczak, J; Zeligowska, E; Mencel, J; Jaskolski, A; Jaskolska, A; Marusiak, J

    2014-06-01

    It has been demonstrated that physical training increases serum brain-derived neurotrophic factor (BDNF) in healthy people. The aim of this study was to establish the effect of physical training on the basal serum level of the BDNF in the Parkinson's disease patients (PD patients) in relation to their health status. Twelve PD patients (mean ± S.E.M: age 70 ± 3 years; body mass 70 ± 2 kg; height 163 ± 3 cm) performed a moderate-intensity interval training (three 1-hour training sessions weekly), lasting 8 weeks. Basal serum BDNF in the PD patients before training amounted to 10,977 ± 756 pg x mL(-1) and after 8 weeks of training it has increased to 14,206 ± 1256 pg x mL(-1) (i.e. by 34%, P=0.03). This was accompanied by an attenuation of total Unified Parkinson's Disease Rating Scale (UPDRS) (P=0.01). The training resulted also in a decrease of basal serum soluble vascular cell adhesion molecule 1 (sVCAM-1) (P=0.001) and serum tumor necrosis factor-α (TNF-α) (P=0.03) levels. We have concluded that the improvement of health status of the Parkinson's disease patients after training could be related to the increase of serum BDNF level caused by the attenuated inflammation in those patients.

  18. Co-morbidity and factor analysis on attention deficit hyperactivity disorder and autism spectrum disorder DSM-IV-derived items

    Directory of Open Access Journals (Sweden)

    Ahmad Ghanizadeh

    2012-01-01

    Full Text Available Background: There is a gap in the literature regarding the extent of possible co-occurrence of attention deficit hyperactivity disorder (ADHD and pervasive developmental disorders (PDD. This study aimed to investigate co-occurring of ADHD in children with PDD. Methods: A clinical sample of 68 children with PDD was assessed according to DSM-IV criteria to make ADHD and/ or PDD diagnoses. All the different types of PDD were included. DSM-IV derived criteria for ADHD and PDD were analyzed. An exploratory factor analysis was conducted. Results: the rate of autism, Asperger syndrome, Rett′s disorder, childhood disintegrative disorder and PDD-NOS (not otherwise specified was 55.4%, 16.9%, 3.1%, 3.1%, 21.5%, respectively. 53.8% of the sample was with ADHD co-morbidity. The rate of ADHD subtypes was 37.1%, 22.9%, and 40.0% for inattentive type, hyperactivity/impulsivity type and combined type, respectively. Conclusion: ADHD and its symptoms highly co-occur with PDD. Meanwhile, the result of factor analysis supports the independence of ADHD and PDD diagnostic criteria.

  19. An investigation into the stability of commercial versus MG63-derived hepatocyte growth factor under flow cultivation conditions.

    Science.gov (United States)

    Meneghello, Giulia; Storm, Michael P; Chaudhuri, Julian B; De Bank, Paul A; Ellis, Marianne J

    2015-03-01

    The scale-up of tissue engineering cell culture must ensure that conditions are maintained while also being cost effective. Here we analyse the stability of hepatocyte growth factor (HGF) to investigate whether concentrations change under dynamic conditions, and compare commercial recombinant human HGF as an additive in 'standard medium', to HGF secreted by the osteosarcoma cell line MG63 as a 'preconditioned medium'. After 3 h under flow conditions, HGF in the standard medium degraded to 40% of its original concentration but HGF in the preconditioned medium remained at 100%. The concentration of secreted HGF was 10 times greater than the working concentration of commercially-available HGF. Thus HGF within this medium has increased stability; MG63-derived HGF should therefore be investigated as a cost-effective alternative to current lyophilised powders for use in in vitro models. Furthermore, we recommend that those intending to use HGF (or other growth factors) should consider similar stability testing before embarking on experiments with media flow.

  20. Brain-derived neurotrophic factor (BDNF) in children with ASD and their parents: a 3-year follow-up.

    Science.gov (United States)

    Francis, K; Dougali, A; Sideri, K; Kroupis, C; Vasdekis, V; Dima, K; Douzenis, A

    2018-05-01

    Several lines of evidence point to a probable relationship between brain-derived neurotrophic factor (BDNF) and autism spectrum disorder (ASD), but studies have yielded inconsistent findings on the BDNF serum level in ASD. The study aimed to assess those levels in children with ASD and their families. BDNF serum levels were measured in 45 ASD children without intellectual disability (ID) and allergies, age 30-42 months and age-matched normal controls. BDNF serum levels in the parents of the ASD subjects were compared to normal controls. BDNF serum levels in the ASD subjects were followed up for 3 years and correlated with adaptive functioning changes. BDNF serum levels were measured to be lower in children with ASD and independent of all the major baseline characteristics of the subjects. Having a child with ASD raises the BDNF levels in parents comparing to controls. Prospectively, no correlation between the change of BDNF variables in time and the change of the Vineland scores was found. Our results contradict those from recent published meta-analyses with the age, the presence of ID and allergies being possible contributing factors. The parents' data indeed point to a role of BDNF in the pathophysiology of ASD. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Evidence that platelet-derived growth factor may be a novel endogenous pyrogen in the central nervous system.

    Science.gov (United States)

    Pelá, I R; Ferreira, M E; Melo, M C; Silva, C A; Coelho, M M; Valenzuela, C F

    2000-05-01

    Platelet-derived growth factor (PDGF) exerts neurotrophic and neuromodulatory actions in the mammalian central nervous system (CNS). Like the cytokines, PDGF primarily signals through tyrosine phosphorylation-dependent pathways that activate multiple intracellular molecules including Janus family kinases. We previously showed that microinjection of PDGF-BB into the lateral ventricle induced a febrile response in rats that was reduced by pretreatment with Win 41662, a potent inhibitor of PDGF receptors (Pelá IR, Ferreira MES, Melo MCC, Silva CAA, and Valenzuela CF. Ann NY Acad Sci 856: 289-293, 1998). In this study, we further characterized the role of PDGF-BB in the febrile response in rats. Microinjection of PDGF-BB into the third ventricle produced a dose-dependent increase in colonic temperature that peaked 3-4 h postinjection. Win 41662 attenuated fever induced by intraperitoneal injection of bacterial lipopolysaccharide, suggesting that endogenous PDGF participates in the febrile response to this exogenous pyrogen. Importantly, febrile responses induced by tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were unchanged by Win 41662. Both indomethacin and dexamethasone blocked the PDGF-BB-induced increase in colonic temperature, and, therefore, we postulate that PDGF-BB may act via prostaglandin- and/or inducible enzyme-dependent pathways. Thus our findings suggest that PDGF-BB is an endogenous CNS mediator of the febrile response in rats.

  2. Progestins inhibit estradiol-induced vascular endothelial growth factor and stromal cell-derived factor 1 in human endometrial stromal cells.

    Science.gov (United States)

    Okada, Hidetaka; Okamoto, Rika; Tsuzuki, Tomoko; Tsuji, Shoko; Yasuda, Katsuhiko; Kanzaki, Hideharu

    2011-09-01

    To investigate whether 17β-estradiol (E(2)) and progestins exert direct effects on vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1/CXCL12) in human endometrial stromal cells (ESCs) and thereby to clarify the regulatory function of these local angiogenic factors in the endometrium. In vitro experiment. Research laboratory at Kansai Medical University. Fourteen patients undergoing hysterectomy for benign reasons. ESCs were cultured with E(2) and/or various clinically relevant progestins (medroxyprogesterone acetate [MPA], norethisterone [NET], levonorgestrel [LNG], dienogest [DNG], and progesterone [P]). The mRNA levels and production of VEGF and SDF-1 were assessed by real-time reverse-transcription polymerase chain reaction and ELISA, respectively. E(2) significantly induced the mRNA levels and protein production of VEGF and SDF-1 in ESCs. MPA could antagonize the E(2)-stimulated effects in a time- and dose-dependent manner, and this effect could be reversed by RU-486 (P receptor antagonist). All of the progestins (MPA, NET, LNG, and DNG; 10(-9) to 10(-7) mol/L) attenuated E(2)-induced VEGF and SDF-1 production, whereas P showed these inhibitory effects only when present in a high concentration (10(-7) mol/L). Progestins have inhibitory effects on E(2)-induced VEGF and SDF-1 in ESCs. These results may indicate a potential mechanism for action of the female sex steroids in the human endometrium that can be helpful for various clinical applications. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Decrease of urinary nerve growth factor but not brain-derived neurotrophic factor in patients with interstitial cystitis/bladder pain syndrome treated with hyaluronic acid.

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    Yuan-Hong Jiang

    Full Text Available To investigate urinary nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF levels in interstitial cystitis/bladder pain syndrome (IC/BPS patients after hyaluronic acid (HA therapy.Thirty-three patients with IC/BPS were prospectively studied; a group of 45 age-matched healthy subjects served as controls. All IC/BPS patients received nine intravesical HA instillations during the 6-month treatment regimen. Urine samples were collected for measuring urinary NGF and BDNF levels at baseline and 2 weeks after the last HA treatment. The clinical parameters including visual analog scale (VAS of pain, daily frequency nocturia episodes, functional bladder capacity (FBC and global response assessment (GRA were recorded. Urinary NGF and BDNF levels were compared between IC/BPS patients and controls at baseline and after HA treatment.Urinary NGF, NGF/Cr, BDNF, and BDNF/Cr levels were significantly higher in IC/BPS patients compared to controls. Both NGF and NGF/Cr levels significantly decreased after HA treatment. Urinary NGF and NGF/Cr levels significantly decreased in the responders with a VAS pain reduction by 2 (both p < 0.05 and the GRA improved by 2 (both p < 0.05, but not in non-responders. Urinary BDNF and BDNF/Cr did not decrease in responders or non-responders after HA therapy.Urinary NGF, but not BDNF, levels decreased significantly after HA therapy; both of these factors remained higher than in controls even after HA treatment. HA had a beneficial effect on IC/BPS, but it was limited. The reduction of urinary NGF levels was significant in responders, with a reduction of pain and improved GRA.

  4. Role of brain-derived neurotrophic factor and nerve growth factor in the regulation of Neuropeptide W in vitro and in vivo.

    Science.gov (United States)

    Wang, Rikang; Yan, Fengxia; Liao, Rifang; Wan, Pei; Little, Peter J; Zheng, Wenhua

    2017-05-15

    Nerve growth factor (NGF) and Brain-derived neurotrophic factor (BDNF) are neurotrophic factors involved in the growth, survival and functioning of neurons. In addition, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has recently been proposed. Neuropeptide W (NPW) is an endogenous peptide ligand for the GPR7 and GPR8 and a stress mediator in the hypothalamus. It activates the HPA axis by working on hypothalamic corticotrophin-releasing hormone (CRH). No information is available about the interrelationships between neurotrophines like NGF/BDNF and NPW. We studied the effect and underlying mechanisms of NGF/BDNF on the production of NPW in PC12 cells and hypothalamus. NGF time- and concentration-dependently stimulated the expression of NPW in PC12 cells. The effect of NGF was blocked by the inhibition of PI3K/Akt signal pathway with specific inhibitors for PI3K or AktsiRNA for Akt while inhibition of ERK pathway had no effect. Moreover, BDNF concentration-dependently induced the expression of NPW mRNA and decreased the expression of NPY mRNA in primary cultured hypothalamic neurons which was also blocked by a PI3K kinase inhibitor. Finally, in vivo study showed that exogenous BDNF injected icv increased NPW production in the hypothalamus and this effect was reversed by a PI3 kinase inhibitor. These results and the fact that BDNF was able to stimulate the expression of CRH demonstrated that neurotrophines can modulate the expression of NPW in neuronal cells via the PI3K/Akt pathway and suggest that BDNF might be involved in functions of the HPA axis, at least in part by modulating the expression of NPW/NPY and CRH. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 15-Deoxy-Δ12,14-prostaglandin J2 and thiazolidinediones transactivate epidermal growth factor and platelet-derived growth factor receptors in vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Ichiki, Toshihiro; Tokunou, Tomotake; Fukuyama, Kae; Iino, Naoko; Masuda, Satoko; Takeshita, Akira

    2004-01-01

    Proliferation of vascular smooth muscle cells (VSMCs) is induced by various mitogens through activation of extracellular signal-regulated protein kinase (ERK) pathway. We recently reported that peroxisome proliferator-activated receptor (PPAR)γ activators such as 15-deoxy-Δ 12,14 -prostaglandin J2 (15-d-PGJ2) and thiazolidinediones (TZDs) activated MEK/ERK pathway through phosphatidylinositol 3-kinase (PI3-K) and induced proliferation of VSMCs. However, the precise mechanisms of PPARγ activators-induced activation of PI3-K/ERK pathway have not been determined. We examined whether transactivation of growth factor receptor is involved in this process. Stimulation of VSMCs with 15-d-PGJ2 or TZDs for 15 min induced phosphorylation of ERK1/2 and Akt. 15-d-PGJ2- or TZDs-induced phosphorylation of ERK1/2 and Akt was inhibited by AG1478, an inhibitor of epidermal growth factor receptor (EGF-R) as well as AG1295, an inhibitor of platelet derived growth factor receptor (PDGF-R). 15-d-PGJ2-induced phosphorylation of both EGF-R and PDGF-R. GM6001, a matrix metalloproteinase inhibitor, and PP2, a Src family protein kinase inhibitor, suppressed 15-d-PGJ2- and TZDs-induced phosphorylation of EGF-R and PDGFβ-R as well as activation of ERK1/2 and Akt. PDGFβ-R was co-immunoprecipitated with EGF-R, regardless of the presence or absence of 15-d-PGJ2. These data suggest that 15-d-PGJ2 and TZDs activate PI3-K/ERK pathway through Src family kinase- and matrix metalloproteinase-dependent transactivation of EGF-R and PDGF-R. Both receptors seemed to associate constitutively. This novel signaling mechanisms may contribute to diverse biological functions of PPARγ activators

  6. Plasma brain-derived neurotrophic factor concentration is a predictor of chronic kidney disease in patients with cardiovascular risk factors - Hyogo Sleep Cardio-Autonomic Atherosclerosis study.

    Directory of Open Access Journals (Sweden)

    Masafumi Kurajoh

    Full Text Available Brain-derived neurotrophic factor (BDNF has been shown to have protective effects against cardiovascular diseases and death through neural and non-neural pathways via tropomyosin-related kinase B signaling. However, it is not known whether plasma BDNF concentration is a predictor of chronic kidney disease (CKD.This study was conducted as a prospective cohort study as part of the Hyogo Sleep Cardio-Autonomic Atherosclerosis.We measured plasma BDNF concentration in 324 patients without CKD, defined as an estimated glomerular filtration rate (eGFR less than 60 ml/min/1.73m2, and with cardiovascular risk factors. As potential confounders, sleep condition, nocturnal hypertension, and autonomic function were quantitatively examined. The patients were followed for a median 37 months (range 2-59 months and occurrence of CKD was noted.Plasma BDNF concentration was significantly and independently associated with CKD development, which occurred in 38 patients (11.7%. Kaplan-Meier analysis revealed that patients with reduced plasma BDNF concentration exhibited a significantly (p = 0.029 greater number of CKD events as compared to those with a higher concentration. Moreover, comparisons of key subgroups showed that the risk of CKD in association with low plasma BDNF concentration was more prominent in patients with a greater reduction of nocturnal systolic blood pressure, better movement index, higher standard deviations of the NN(RR interval or average NN(RR interval for each 5-minute period, and without past cardiovascular disease events, smoking habit, or albuminuria.Plasma BDNF concentration is an independent predictor for development of CKD in patients with cardiovascular risk factors.

  7. Pivotal Role of Brain-Derived Neurotrophic Factor Secreted by Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage in Newborn Rats.

    Science.gov (United States)

    Ahn, So Yoon; Chang, Yun Sil; Sung, Dong Kyung; Sung, Se In; Ahn, Jee-Yin; Park, Won Soon

    2017-01-24

    Mesenchymal stem cell (MSC) transplantation protects against neonatal severe intraventricular hemorrhage (IVH)-induced brain injury by a paracrine rather than regenerative mechanism; however, the paracrine factors involved and their roles have not yet been delineated. This study aimed to identify the paracrine mediator(s) and to determine their role in mediating the therapeutic effects of MSCs in severe IVH. We first identified significant upregulation of brain-derived neurotrophic factor (BDNF) in MSCs compared with fibroblasts, in both DNA and antibody microarrays, after thrombin exposure. We then knocked down BDNF in MSCs by transfection with small interfering (si)RNA specific for human BDNF. The therapeutic effects of MSCs with or without BDNF knockdown were evaluated in vitro in rat neuronal cells challenged with thrombin, and in vivo in newborn Sprague-Dawley rats by injecting 200 μl of blood on postnatal day 4 (P4), and transplanting MSCs (1 × 105 cells) intraventricularly on P6. siRNA-induced BDNF knockdown abolished the in vitro benefits of MSCs on thrombin-induced neuronal cell death. BDNF knockdown also abolished the in vivo protective effects against severe IVH-induced brain injuries such as the attenuation of posthemorrhagic hydrocephalus, impaired behavioral test performance, increased astrogliosis, increased number of TUNEL cells, ED-1+ cells, and inflammatory cytokines, and reduced myelin basic protein expression. Our data indicate that BDNF secreted by transplanted MSCs is one of the critical paracrine factors that play a seminal role in attenuating severe IVH-induced brain injuries in newborn rats.

  8. Host-derived, pore-forming toxin-like protein and trefoil factor complex protects the host against microbial infection.

    Science.gov (United States)

    Xiang, Yang; Yan, Chao; Guo, Xiaolong; Zhou, Kaifeng; Li, Sheng'an; Gao, Qian; Wang, Xuan; Zhao, Feng; Liu, Jie; Lee, Wen-Hui; Zhang, Yun

    2014-05-06

    Aerolysins are virulence factors belonging to the bacterial β-pore-forming toxin superfamily. Surprisingly, numerous aerolysin-like proteins exist in vertebrates, but their biological functions are unknown. βγ-CAT, a complex of an aerolysin-like protein subunit (two βγ-crystallin domains followed by an aerolysin pore-forming domain) and two trefoil factor subunits, has been identified in frogs (Bombina maxima) skin secretions. Here, we report the rich expression of this protein, in the frog blood and immune-related tissues, and the induction of its presence in peritoneal lavage by bacterial challenge. This phenomena raises the possibility of its involvement in antimicrobial infection. When βγ-CAT was administrated in a peritoneal infection model, it greatly accelerated bacterial clearance and increased the survival rate of both frogs and mice. Meanwhile, accelerated Interleukin-1β release and enhanced local leukocyte recruitments were determined, which may partially explain the robust and effective antimicrobial responses observed. The release of interleukin-1β was potently triggered by βγ-CAT from the frog peritoneal cells and murine macrophages in vitro. βγ-CAT was rapidly endocytosed and translocated to lysosomes, where it formed high molecular mass SDS-stable oligomers (>170 kDa). Lysosomal destabilization and cathepsin B release were detected, which may explain the activation of caspase-1 inflammasome and subsequent interleukin-1β maturation and release. To our knowledge, these results provide the first functional evidence of the ability of a host-derived aerolysin-like protein to counter microbial infection by eliciting rapid and effective host innate immune responses. The findings will also largely help to elucidate the possible involvement and action mechanisms of aerolysin-like proteins and/or trefoil factors widely existing in vertebrates in the host defense against pathogens.

  9. Local delivery of glial cell line-derived neurotrophic factor improves facial nerve regeneration after late repair.

    Science.gov (United States)

    Barras, Florian M; Kuntzer, Thierry; Zurn, Anne D; Pasche, Philippe

    2009-05-01

    Facial nerve regeneration is limited in some clinical situations: in long grafts, by aged patients, and when the delay between nerve lesion and repair is prolonged. This deficient regeneration is due to the limited number of regenerating nerve fibers, their immaturity and the unresponsiveness of Schwann cells after a long period of denervation. This study proposes to apply glial cell line-derived neurotrophic factor (GDNF) on facial nerve grafts via nerve guidance channels to improve the regeneration. Two situations were evaluated: immediate and delayed grafts (repair 7 months after the lesion). Each group contained three subgroups: a) graft without channel, b) graft with a channel without neurotrophic factor; and c) graft with a GDNF-releasing channel. A functional analysis was performed with clinical observation of facial nerve function, and nerve conduction study at 6 weeks. Histological analysis was performed with the count of number of myelinated fibers within the graft, and distally to the graft. Central evaluation was assessed with Fluoro-Ruby retrograde labeling and Nissl staining. This study showed that GDNF allowed an increase in the number and the maturation of nerve fibers, as well as the number of retrogradely labeled neurons in delayed anastomoses. On the contrary, after immediate repair, the regenerated nerves in the presence of GDNF showed inferior results compared to the other groups. GDNF is a potent neurotrophic factor to improve facial nerve regeneration in grafts performed several months after the nerve lesion. However, GDNF should not be used for immediate repair, as it possibly inhibits the nerve regeneration.

  10. Adhesion of nitrile rubber to UV-assisted surface chemical modified PET fabric, part II: Interfacial characterization of MDI grafted PET

    Science.gov (United States)

    Razavizadeh, Mahmoud; Jamshidi, Masoud

    2016-08-01

    Fiber to rubber adhesion is an important subject in rubber industry. It is well known that surface treatment (i.e. physical, mechanical and chemical) is an effective method to improve interfacial bonding of fibers and/or fabrics to rubbers. UV irradiation is an effective method which has been used to increase fabric-rubber interfacial interactions. In this research UV assisted chemical modification of PET fabrics was used to increase PET to nitrile rubber (NBR) adhesion. Nitrile rubber is a perfect selection as fuel and oil resistant rubber. However it has weak bonding to PET fabric. For this purpose PET fabric was carboxylated under UV irradiation and then methylenediphenyl diisocyanate (MDI) was grafted on carboxylated PET. The chemical composition of the fabric before and after surface treatment was investigated by X-ray photoelectron spectroscopy (XPS). The sectional morphology of the experimental PET fibers and the interface between rubber compound and PET fabric was studied using scanning electron microscope (SEM). The morphology and structure of the product were analyzed by an energy dispersive X-ray spectrometer (EDX). FTIR-ATR and H NMR analysis were used to assess surface modifications on the PET irradiated fabrics.

  11. The role of growth factors in maintenance of stemness in bone marrow-derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Young Woo; Oh, Ji-Eun [Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Lee, Jong In [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Baik, Soon Koo [Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Department of Internal Medicine, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Rhee, Ki-Jong [Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei Univ., Wonju (Korea, Republic of); Shin, Ha Cheol; Kim, Yong Man [Pharmicell Co., Ltd., Sungnam (Korea, Republic of); Ahn, Chan Mug [Department of Basic Science, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Kong, Jee Hyun [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Kim, Hyun Soo, E-mail: khsmd@pharmicell.com [Pharmicell Co., Ltd., Sungnam (Korea, Republic of); Shim, Kwang Yong, E-mail: kyshim@yonsei.ac.kr [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of)

    2014-02-28

    Highlights: • Expression of FGF-2, FGF-4, EGF, and HGF decreased during long-term culture of BMSCs. • Loss of growth factors induced autophagy, senescence and decrease of stemness. • FGF-2 increased proliferation potential via AKT and ERK activation in BMSCs. • FGF-2 suppressed LC3-II expression and down-regulated senescence of BMSCs. • HGF was important in maintenance of the differentiation potential of BMSCs. - Abstract: Mesenchymal stem cells (MSCs) are an active topic of research in regenerative medicine due to their ability to secrete a variety of growth factors and cytokines that promote healing of damaged tissues and organs. In addition, these secreted growth factors and cytokines have been shown to exert an autocrine effect by regulating MSC proliferation and differentiation. We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs). Proliferation and differentiation potentials of BMSCs treated with these growth factors for 2 months were evaluated and compared to BMSCs treated with FGF-2, which increased proliferation of BMSCs. FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2 months, while EGF and HGF increased proliferation of BMSCs by less than 2.8-fold. Interestingly, differentiation potential, especially adipogenesis, was maintained only by HGF treatment. Treatment with FGF-2 rapidly induced activation of AKT and later induced ERK activation. The basal level of phosphorylated ERK increased during serial passage of BMSCs treated with FGF-2. The expression of LC3-II, an autophagy marker, was gradually increased and the population of senescent cells was increased dramatically at passage 7 in non-treated controls. But FGF-2 and FGF-4 suppressed LC3-II expression and down-regulated senescent cells during long-term (i.e. 2 month) cultures. Taken together, depletion of growth factors during serial passage

  12. The role of growth factors in maintenance of stemness in bone marrow-derived mesenchymal stem cells

    International Nuclear Information System (INIS)

    Eom, Young Woo; Oh, Ji-Eun; Lee, Jong In; Baik, Soon Koo; Rhee, Ki-Jong; Shin, Ha Cheol; Kim, Yong Man; Ahn, Chan Mug; Kong, Jee Hyun; Kim, Hyun Soo; Shim, Kwang Yong

    2014-01-01

    Highlights: • Expression of FGF-2, FGF-4, EGF, and HGF decreased during long-term culture of BMSCs. • Loss of growth factors induced autophagy, senescence and decrease of stemness. • FGF-2 increased proliferation potential via AKT and ERK activation in BMSCs. • FGF-2 suppressed LC3-II expression and down-regulated senescence of BMSCs. • HGF was important in maintenance of the differentiation potential of BMSCs. - Abstract: Mesenchymal stem cells (MSCs) are an active topic of research in regenerative medicine due to their ability to secrete a variety of growth factors and cytokines that promote healing of damaged tissues and organs. In addition, these secreted growth factors and cytokines have been shown to exert an autocrine effect by regulating MSC proliferation and differentiation. We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs). Proliferation and differentiation potentials of BMSCs treated with these growth factors for 2 months were evaluated and compared to BMSCs treated with FGF-2, which increased proliferation of BMSCs. FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2 months, while EGF and HGF increased proliferation of BMSCs by less than 2.8-fold. Interestingly, differentiation potential, especially adipogenesis, was maintained only by HGF treatment. Treatment with FGF-2 rapidly induced activation of AKT and later induced ERK activation. The basal level of phosphorylated ERK increased during serial passage of BMSCs treated with FGF-2. The expression of LC3-II, an autophagy marker, was gradually increased and the population of senescent cells was increased dramatically at passage 7 in non-treated controls. But FGF-2 and FGF-4 suppressed LC3-II expression and down-regulated senescent cells during long-term (i.e. 2 month) cultures. Taken together, depletion of growth factors during serial passage

  13. Platelet-, monocyte-derived and tissue factor-carrying circulating microparticles are related to acute myocardial infarction severity.

    Directory of Open Access Journals (Sweden)

    Gemma Chiva-Blanch

    Full Text Available Circulating microparticles (cMPs are phospholipid-rich vesicles released from cells when activated or injured, and contribute to the formation of intracoronary thrombi. Tissue factor (TF, CD142 is the main trigger of fibrin formation and TF-carrying cMPs are considered one of the most procoagulant cMPs. Similar types of atherosclerotic lesions may lead to different types of AMI, although the mechanisms behind are unresolved. Therefore, we aimed to investigate the phenotype of cMPs found in plasma of ACS patients and its relation to AMI severity and thrombotic burden.In a cross-sectional study, two hundred patients aged 75±4 years were included in the study 2-8 weeks after suffering an AMI. Annexin V positive (AV+-cMPs derived from blood and vascular cells were measured by flow cytometry. Plasma procoagulant activity (TF-PCA was measured through a chromogenic assay.STEMI patients (n = 75 showed higher levels of platelet-derived cMPs [CD61+/AV+, CD31+/AV+, CD42b+/AV+ and CD31+/CD42b+/AV+, P = 0.048, 0.038, 0.009 and 0.006, respectively], compared to NSTEMI patients (n = 125. Patients who suffered a heart failure during AMI (n = 17 had increased levels of platelet (CD61+-and monocyte (CD14+-derived cMPs carrying TF (CD142+ (P<0.0001 and 0.004, respectively. Additionally, NYHA class III (n = 23 patients showed higher levels of CD142+/AV+, CD14+/AV+ and CD14+/CD142+/AV+ cMPs than those in class I/II (P = 0.001, 0.015 and 0.014, respectively. The levels of these cMPs positively correlated with TF-PCA (r≥0.166, P≤0.027, all.Platelets and monocytes remain activated in AMI patients treated as per guidelines and release cMPs that discriminate AMI severity. Therefore, TF-MPs, and platelet- and monocyte-MPs may reflect thrombotic burden in AMI patients.

  14. Milk fat globule-epidermal growth factor-factor VIII-derived peptide MSP68 is a cytoskeletal immunomodulator of neutrophils that inhibits Rac1.

    Science.gov (United States)

    Hendricks, Louie; Aziz, Monowar; Yang, Weng-Lang; Nicastro, Jeffrey; Coppa, Gene F; Symons, Marc; Wang, Ping

    2017-02-01

    Prolonged neutrophil infiltration leads to exaggerated inflammation and tissue damage during sepsis. Neutrophil migration requires rearrangement of their cytoskeleton. Milk fat globule-epidermal growth factor-factor VIII-derived short peptide 68 (MSP68) has recently been shown to be beneficial in sepsis-induced tissue injury and mortality. We hypothesize that MSP68 inhibits neutrophil migration by modulating small GTPase Rac1-dependent cytoskeletal rearrangements. Bone marrow-derived neutrophils (BMDNs) or whole lung digest isolated neutrophils were isolated from 8 to 10 wk old C57BL/6 mice by Percoll density gradient centrifugation. The purity of BMDN was verified by flow cytometry with CD11b/Gr-1 staining. Neutrophils were stimulated with N-formylmethionine-leucine-phenylalanine (f-MLP) (10 nM) in the presence or absence of MSP68 at 10 nM or cecal ligation and puncture (CLP) was used to induce sepsis, and MSP68 was administered at 1 mg/kg intravenously. Cytoskeletal organization was assessed by phalloidin staining, followed by analysis using fluorescence microscopy. Activity of the Rac1 GTPase in f-MLP or CLP-activated BMDN in the presence or absence of MSP68 was assessed by GTPase enzyme-linked immunosorbent assay. Mitogen-activated protein (MAP) kinase activity was determined by western blot densitometry. BMDN treatment with f-MLP increased cytoskeletal remodeling as revealed by the localization of filamentous actin to the periphery of the neutrophil. By contrast, cells pretreated with MSP68 had considerably reduced filamentous actin polymerization. Cytoskeletal spreading is associated with the activation of the small GTPase Rac1. We found BMDN-treated with f-MLP or that were exposed to sepsis by CLP had increased Rac1 signaling, whereas the cells pretreated with MSP68 had significantly reduced Rac1 activation (P Rac1-MAP kinase-mediated neutrophil motility. Thus, MSP68 is a novel therapeutic candidate for regulating inflammation and tissue damage caused

  15. Transforming growth factor β inhibits platelet derived growth factor-induced vascular smooth muscle cell proliferation via Akt-independent, Smad-mediated cyclin D1 downregulation.

    Directory of Open Access Journals (Sweden)

    Abel Martin-Garrido

    Full Text Available In adult tissue, vascular smooth muscle cells (VSMCs exist in a differentiated phenotype, which is defined by the expression of contractile proteins and lack of proliferation. After vascular injury, VSMC adopt a synthetic phenotype associated with proliferation, migration and matrix secretion. The transition between phenotypes is a consequence of the extracellular environment, and in particular, is regulated by agonists such as the pro-differentiating cytokine transforming growth factor β (TGFβ and the pro-proliferative cytokine platelet derived growth factor (PDGF. In this study, we investigated the interplay between TGFβ and PDGF with respect to their ability to regulate VSMC proliferation. Stimulation of human aortic VSMC with TGFβ completely blocked proliferation induced by all isoforms of PDGF, as measured by DNA synthesis and total cell number. Mechanistically, PDGF-induced Cyclin D1 mRNA and protein expression was inhibited by TGFβ. TGFβ had no effect on PDGF activation of its receptor and ERK1/2, but inhibited Akt activation. However, constitutively active Akt did not reverse the inhibitory effect of TGFβ on Cyclin D1 expression even though inhibition of the proteasome blocked the effect of TGFβ. siRNA against Smad4 completely reversed the inhibitory effect of TGFβ on PDGF-induced Cyclin D1 expression and restored proliferation in response to PDGF. Moreover, siRNA against KLF5 prevented Cyclin D1 upregulation by PDGF and overexpression of KLF5 partially reversed TGFβ-induced inhibition of Cyclin D1 expression. Taken together, our results demonstrate that KLF5 is required for PDGF-induced Cyclin D1 expression, which is inhibited by TGFβ via a Smad dependent mechanism, resulting in arrest of VSMCs in the G1 phase of the cell cycle.

  16. Transforming growth factor β inhibits platelet derived growth factor-induced vascular smooth muscle cell proliferation via Akt-independent, Smad-mediated cyclin D1 downregulation.

    Science.gov (United States)

    Martin-Garrido, Abel; Williams, Holly C; Lee, Minyoung; Seidel-Rogol, Bonnie; Ci, Xinpei; Dong, Jin-Tang; Lassègue, Bernard; Martín, Alejandra San; Griendling, Kathy K

    2013-01-01

    In adult tissue, vascular smooth muscle cells (VSMCs) exist in a differentiated phenotype, which is defined by the expression of contractile proteins and lack of proliferation. After vascular injury, VSMC adopt a synthetic phenotype associated with proliferation, migration and matrix secretion. The transition between phenotypes is a consequence of the extracellular environment, and in particular, is regulated by agonists such as the pro-differentiating cytokine transforming growth factor β (TGFβ) and the pro-proliferative cytokine platelet derived growth factor (PDGF). In this study, we investigated the interplay between TGFβ and PDGF with respect to their ability to regulate VSMC proliferation. Stimulation of human aortic VSMC with TGFβ completely blocked proliferation induced by all isoforms of PDGF, as measured by DNA synthesis and total cell number. Mechanistically, PDGF-induced Cyclin D1 mRNA and protein expression was inhibited by TGFβ. TGFβ had no effect on PDGF activation of its receptor and ERK1/2, but inhibited Akt activation. However, constitutively active Akt did not reverse the inhibitory effect of TGFβ on Cyclin D1 expression even though inhibition of the proteasome blocked the effect of TGFβ. siRNA against Smad4 completely reversed the inhibitory effect of TGFβ on PDGF-induced Cyclin D1 expression and restored proliferation in response to PDGF. Moreover, siRNA against KLF5 prevented Cyclin D1 upregulation by PDGF and overexpression of KLF5 partially reversed TGFβ-induced inhibition of Cyclin D1 expression. Taken together, our results demonstrate that KLF5 is required for PDGF-induced Cyclin D1 expression, which is inhibited by TGFβ via a Smad dependent mechanism, resulting in arrest of VSMCs in the G1 phase of the cell cycle.

  17. Growth/differentiation factor-5 significantly enhances periodontal wound healing/regeneration compared with platelet-derived growth factor-BB in dogs.

    Science.gov (United States)

    Kwon, Hyuk-Rak; Wikesjö, Ulf M E; Park, Jung-Chul; Kim, Young-Taek; Bastone, Patrizia; Pippig, Susanne D; Kim, Chong-Kwan

    2010-08-01

    Recombinant human growth/differentiation factor-5 (rhGDF-5) in a particulate beta-tricalcium phosphate (beta-TCP) carrier is being evaluated to support periodontal regeneration. The objective of this study was to evaluate periodontal wound healing/regeneration following an established clinical (benchmark) protocol including surgical implantation of rhGDF-5/beta-TCP in comparison with that following implantation of recombinant human platelet-derived growth factor-BB (rhPDGF) combined with a particulate beta-TCP biomaterial using an established canine defect model. Bilateral, 4 x 5 mm (width x depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in five adult Beagle dogs. Defect sites were randomized to receive rhGDF-5/beta-TCP or the rhPDGF construct followed by wound closure for primary intention healing. The animals were sacrificed following an 8-week healing interval for histological and histometric examination. Clinical healing was generally uneventful. Sites receiving rhGDF-5/beta-TCP exhibited a significantly enhanced cementum formation compared with sites receiving the rhPDGF construct, averaging (+/-SD) 4.49+/-0.48 versus 2.72+/-0.91 mm (palveolar bone. Both protocols displayed beta-TCP residues apparently undergoing resorption. Application of both materials appears safe, as they were associated with limited, if any, adverse events. rhGDF-5/beta-TCP shows a significant potential to support/accelerate periodontal wound healing/regeneration. Application of rhGDF-5/beta-TCP appears safe and should be further evaluated in human clinical trials.

  18. Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Kao, Ying-Hsien; Chen, Po-Han; Sun, Cheuk-Kwan; Chang, Yo-Chen; Lin, Yu-Chun; Tsai, Ming-Shian; Lee, Po-Huang; Cheng, Cheng-I

    2018-02-21

    Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration. ©2018 The Author(s).

  19. Elevated plasma pigment epithelium-derived factor in children with type 2 diabetes mellitus is attributable to obesity.

    Science.gov (United States)

    Tryggestad, Jeanie B; Wang, Joshua J; Zhang, Sarah X; Thompson, David M; Short, Kevin R

    2015-12-01

    Pigment epithelium-derived factor (PEDF) is a member of the serpin family secreted by adipocytes. Plasma PEDF is increased in obese children and adults. Adults with type 2 diabetes mellitus (T2DM) have higher circulating PEDF but there are no reports in children with T2DM. To compare PEDF concentration in children with T2DM to normal weight and obese children without T2DM and determine associations with anthropometric or serum factors. Participants were 34 obese children with T2DM diagnosed by American Diabetes Association (ADA) criteria, 61 normal weight [body mass index (BMI) 25-75 percentile] and 63 obese (BMI ≥ 95 percentile) children of age 8-18 yr. Plasma PEDF was measured in fasting plasma samples. Anthropometric, serum, and body composition (dual-energy x-ray absorptiometry, DXA) data were obtained for each subject to identify potential predictor variables. PEDF was 55% higher (p = 0.001) in the T2DM group compared with normal weight children, but did not differ from obese children. In the T2DM group, fat mass and lean mass both individually predicted PEDF (r² = 0.22 and 0.17, p = 0.02 and p obese groups, therefore, obesity, rather than diabetes, may account for the higher PEDF in children with T2DM compared with normal weight children. PEDF was positively associated with both lean mass and fat mass both of which may contribute to the circulating level of the protein, and potentially to PEDF's association with insulin resistance in obese children with and without diabetes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Evidence of associations between brain-derived neurotrophic factor (BDNF serum levels and gene polymorphisms with tinnitus

    Directory of Open Access Journals (Sweden)

    Aysun Coskunoglu

    2017-01-01

    Full Text Available Background: Brain-derived neurotrophic factor (BDNF gene polymorphisms are associated with abnormalities in regulation of BDNF secretion. Studies also linked BDNF polymorphisms with changes in brainstem auditory-evoked response test results. Furthermore, BDNF levels are reduced in tinnitus, psychiatric disorders, depression, dysthymic disorder that may be associated with stress, conversion disorder, and suicide attempts due to crises of life. For this purpose, we investigated whether there is any role of BDNF changes in the pathophysiology of tinnitus. Materials and Methods: In this study, we examined the possible effects of BDNF variants in individuals diagnosed with tinnitus for more than 3 months. Fifty-two tinnitus subjects between the ages of 18 and 55, and 42 years healthy control subjects in the same age group, who were free of any otorhinolaryngology and systemic disease, were selected for examination. The intensity of tinnitus and depression was measured using the tinnitus handicap inventory, and the differential diagnosis of psychiatric diagnoses made using the Structured Clinical Interview for Fourth Edition of Mental Disorders. BDNF gene polymorphism was analyzed in the genomic deoxyribonucleic acid (DNA samples extracted from the venous blood, and the serum levels of BDNF were measured. One-way analysis of variance and Chi-squared tests were applied. Results: Serum BDNF level was found lower in the tinnitus patients than controls, and it appeared that there is no correlation between BDNF gene polymorphism and tinnitus. Conclusions: This study suggests neurotrophic factors such as BDNF may have a role in tinnitus etiology. Future studies with larger sample size may be required to further confirm our results.

  1. Lack of Postprandial Peak in Brain-Derived Neurotrophic Factor in Adults with Prader-Willi Syndrome.

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    Marta Bueno

    Full Text Available Prader-Willi syndrome (PWS is characterized by severe hyperphagia. Brain-derived neurotrophic factor (BDNF and leptin are reciprocally involved in energy homeostasis.To analyze the role of BDNF and leptin in satiety in genetic subtypes of PWS.Experimental study.University hospital.90 adults: 30 PWS patients; 30 age-sex-BMI-matched obese controls; and 30 age-sex-matched lean controls.Subjects ingested a liquid meal after fasting ≥10 hours.Leptin and BDNF levels in plasma extracted before ingestion and 30', 60', and 120' after ingestion. Hunger, measured on a 100-point visual analogue scale before ingestion and 60' and 120' after ingestion.Fasting BDNF levels were lower in PWS than in controls (p = 0.05. Postprandially, PWS patients showed only a truncated early peak in BDNF, and their BDNF levels at 60' and 120' were lower compared with lean controls (p<0.05. Leptin was higher in PWS patients than in controls at all time points (p<0.001. PWS patients were hungrier than controls before and after eating. The probability of being hungry was associated with baseline BDNF levels: every 50-unit increment in BDNF decreased the odds of being hungry by 22% (OR: 0.78, 95%CI: 0.65-0.94. In uniparental disomy, the odds of being hungry decreased by 66% (OR: 0.34, 90%CI: 0.13-0.9. Postprandial leptin patterns did no differ among genetic subtypes.Low baseline BDNF levels and lack of postprandial peak may contribute to persistent hunger after meals. Uniparental disomy is the genetic subtype of PWS least affected by these factors.

  2. Using low-risk factors to generate non-integrated human induced pluripotent stem cells from urine-derived cells.

    Science.gov (United States)

    Wang, Linli; Chen, Yuehua; Guan, Chunyan; Zhao, Zhiju; Li, Qiang; Yang, Jianguo; Mo, Jian; Wang, Bin; Wu, Wei; Yang, Xiaohui; Song, Libing; Li, Jun

    2017-11-02

    Because the lack of an induced pluripotent stem cell (iPSC) induction system with optimal safety and efficiency limits the application of these cells, development of such a system is important. To create such an induction system, we screened a variety of reprogrammed plasmid combinations and multiple compounds and then verified the system's feasibility using urine cells from different individuals. We also compared large-scale iPSC chromosomal variations and expression of genes associated with genomic stability between this system and the traditional episomal system using karyotype and quantitative reverse transcription polymerase chain reaction analyses. We developed a high-efficiency episomal system, the 6F/BM1-4C system, lacking tumorigenic factors for human urine-derived cell (hUC) reprogramming. This system includes six low-risk factors (6F), Oct4, Glis1, Klf4, Sox2, L-Myc, and the miR-302 cluster. Transfected hUCs were treated with four compounds (4C), inhibitor of lysine-demethylase1, methyl ethyl ketone, glycogen synthase kinase 3 beta, and histone deacetylase, within a short time period. Comparative analysis revealed significantly decreased chromosomal variation in iPSCs and significantly increased Sirt1 expression compared with iPSCs induced using the traditional episomal system. The 6F/BM1-4C system effectively induces reprogramming of urine cells in samples obtained from different individuals. iPSCs induced using the 6F/BM1-4C system are more stable at the cytogenetic level and have potential value for clinical application.

  3. Binding characteristics of brain-derived neurotrophic factor to its receptors on neurons from the chick embryo

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Tebar, A.; Barde, Y.A.

    1988-09-01

    Brain-derived neurotrophic factor (BDNF), a protein known to support the survival of embryonic sensory neurons and retinal ganglion cells, was derivatized with 125I-Bolton-Hunter reagent and obtained in a biologically active, radioactive form (125I-BDNF). Using dorsal root ganglion neurons from chick embryos at 9 d of development, the basic physicochemical parameters of the binding of 125I-BDNF with its receptors were established. Two different classes of receptors were found, with dissociation constants of 1.7 x 10(-11) M (high-affinity receptors) and 1.3 x 10(-9) M (low-affinity receptors). Unlabeled BDNF competed with 125I-BDNF for binding to the high-affinity receptors with an inhibition constant essentially identical to the dissociation constant of the labeled protein: 1.2 x 10(-11) M. The association and dissociation rates from both types of receptors were also determined, and the dissociation constants calculated from these kinetic experiments were found to correspond to the results obtained from steady-state binding. The number of high-affinity receptors (a few hundred per cell soma) was 15 times lower than that of low-affinity receptors. No high-affinity receptors were found on sympathetic neurons, known not to respond to BDNF, although specific binding of 125I-BDNF to these cells was detected at a high concentration of the radioligand. These results are discussed and compared with those obtained with nerve growth factor on the same neuronal populations.

  4. Serum brain-derived neurotrophic factor (BDNF) across pregnancy and postpartum: Associations with race, depressive symptoms, and low birth weight.

    Science.gov (United States)

    Christian, Lisa M; Mitchell, Amanda M; Gillespie, Shannon L; Palettas, Marilly

    2016-12-01

    Brain-derived neurotrophic factor (BDNF) is implicated as a causal factor in major depression and is critical to placental development during pregnancy. Longitudinal data on BDNF across the perinatal period are lacking. These data are of interest given the potential implications for maternal mood and fetal growth, particularly among Black women who show ∼2-fold greater risk for delivering low birth weight infants. Serum BDNF, serum cortisol, and depressive symptoms (per CES-D) were assessed during each trimester and 4-11 weeks postpartum among 139 women (77 Black, 62 White). Low birth weight (BDNF declined considerably from 1st through 3rd trimesters (ps≤0.008) and subsequently increased at postpartum (pBDNF during the 1st trimester, 2nd trimester, and postpartum (ps≤0.032) as well as lower serum cortisol during the 2nd and 3rd trimester (ps≤0.01). Higher serum cortisol was concurrently associated with lower serum BDNF in the 2nd trimester only (pBDNF at both the 2nd and 3rd trimester was negatively associated with 3rd trimester depressive symptoms (ps≤0.02). In addition, women delivering low versus healthy weight infants showed significantly lower serum BDNF in the 3rd trimester (p=0.004). Women delivering low versus healthy weight infants did not differ in depressive symptoms at any time point during pregnancy (ps≥0.34). Serum BDNF declines considerably across pregnancy in Black and White women, with overall higher levels in Blacks. Lower serum BDNF in late pregnancy corresponds with higher depressive symptoms and risk for low birth weight in Black and White women. However, the predictive value of serum BDNF in pregnancy is specific to within-race comparisons. Potential links between racial differences in serum BDNF and differential pregnancy-related cortisol adaptation require further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Evidence of associations between brain-derived neurotrophic factor (BDNF) serum levels and gene polymorphisms with tinnitus.

    Science.gov (United States)

    Coskunoglu, Aysun; Orenay-Boyacioglu, Seda; Deveci, Artuner; Bayam, Mustafa; Onur, Ece; Onan, Arzu; Cam, Fethi S

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) gene polymorphisms are associated with abnormalities in regulation of BDNF secretion. Studies also linked BDNF polymorphisms with changes in brainstem auditory-evoked response test results. Furthermore, BDNF levels are reduced in tinnitus, psychiatric disorders, depression, dysthymic disorder that may be associated with stress, conversion disorder, and suicide attempts due to crises of life. For this purpose, we investigated whether there is any role of BDNF changes in the pathophysiology of tinnitus. In this study, we examined the possible effects of BDNF variants in individuals diagnosed with tinnitus for more than 3 months. Fifty-two tinnitus subjects between the ages of 18 and 55, and 42 years healthy control subjects in the same age group, who were free of any otorhinolaryngology and systemic disease, were selected for examination. The intensity of tinnitus and depression was measured using the tinnitus handicap inventory, and the differential diagnosis of psychiatric diagnoses made using the Structured Clinical Interview for Fourth Edition of Mental Disorders. BDNF gene polymorphism was analyzed in the genomic deoxyribonucleic acid (DNA) samples extracted from the venous blood, and the serum levels of BDNF were measured. One-way analysis of variance and Chi-squared tests were applied. Serum BDNF level was found lower in the tinnitus patients than controls, and it appeared that there is no correlation between BDNF gene polymorphism and tinnitus. This study suggests neurotrophic factors such as BDNF may have a role in tinnitus etiology. Future studies with larger sample size may be required to further confirm our results.

  6. Binding characteristics of brain-derived neurotrophic factor to its receptors on neurons from the chick embryo

    International Nuclear Information System (INIS)

    Rodriguez-Tebar, A.; Barde, Y.A.

    1988-01-01

    Brain-derived neurotrophic factor (BDNF), a protein known to support the survival of embryonic sensory neurons and retinal ganglion cells, was derivatized with 125I-Bolton-Hunter reagent and obtained in a biologically active, radioactive form (125I-BDNF). Using dorsal root ganglion neurons from chick embryos at 9 d of development, the basic physicochemical parameters of the binding of 125I-BDNF with its receptors were established. Two different classes of receptors were found, with dissociation constants of 1.7 x 10(-11) M (high-affinity receptors) and 1.3 x 10(-9) M (low-affinity receptors). Unlabeled BDNF competed with 125I-BDNF for binding to the high-affinity receptors with an inhibition constant essentially identical to the dissociation constant of the labeled protein: 1.2 x 10(-11) M. The association and dissociation rates from both types of receptors were also determined, and the dissociation constants calculated from these kinetic experiments were found to correspond to the results obtained from steady-state binding. The number of high-affinity receptors (a few hundred per cell soma) was 15 times lower than that of low-affinity receptors. No high-affinity receptors were found on sympathetic neurons, known not to respond to BDNF, although specific binding of 125I-BDNF to these cells was detected at a high concentration of the radioligand. These results are discussed and compared with those obtained with nerve growth factor on the same neuronal populations

  7. Brain-Derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study

    Science.gov (United States)

    Diniz, Breno Satler; Reynolds, Charles F.; Begley, Amy; Dew, Mary Amanda; Anderson, Stewart J.; Lotrich, Francis; Erickson, Kirk I.; Lopez, Oscar; Aizenstein, Howard; Sibille, Etienne L.; Butters, Meryl A.

    2014-01-01

    Changes in brain-derived neurotrophic factor (BDNF) level are implicated in the pathophysiology of cognitive decline in depression and neurodegenerative disorders in older adults. We aimed to evaluate the longitudinal association over two years between BDNF and persistent cognitive decline in individuals with remitted late-life depression and Mild Cognitive Impairment (LLD+MCI) compared to either individuals with remitted LLD and no cognitive decline (LLD+NCD) or never-depressed, cognitively normal, elderly control participants. We additionally evaluated the effect of double-blind, placebo-controlled donepezil treatment on BDNF levels in all of the remitted LLD participants (across the levels of cognitive function). We included 160 elderly participants in this study (72 LLD+NCD, 55 LLD+MCI and 33 never-depressed cognitively normal elderly participants). At the same visits, cognitive assessments were conducted and blood sampling to determine serum BDNF levels were collected at baseline assessment and after one and two years of follow-up. We utilized repeated measure, mixed effect models to assess: (1) the effects of diagnosis (LLD+MCI, LLD+NCD, and controls), time, and their interaction on BDNF levels; and (2) the effects of donepezil treatment (donepezil vs. placebo), time, baseline diagnosis (LLD+MCI vs. LLD+NCD), and interactions between these contrasts on BDNF levels. We found a significant effect of time on BDNF level (p=0.02) and a significant decline in BDNF levels over 2 years of follow-up in participants with LLD+MCI (p=0.004) and controls (p=0.04). We found no effect of donepezil treatment on BDNF level. The present results suggest that aging is an important factor related to decline in BDNF level. PMID:24290367

  8. Brain-derived neurotrophic factor is increased in serum and skin levels of patients with chronic spontaneous urticaria.

    Science.gov (United States)

    Rössing, K; Novak, N; Mommert, S; Pfab, F; Gehring, M; Wedi, B; Kapp, A; Raap, U

    2011-10-01

    Chronic spontaneous urticaria is triggered by many direct and indirect aggravating factors including autoreactive/autoimmune mechanisms, infections, non-allergic and pseudoallergic intolerance reactions. However, the role of neuroimmune mechanisms in chronic spontaneous urticaria so far is unclear. Thus, we wanted to address the regulation of the neurotrophin brain-derived neurotrophic factor (BDNF) in serum and inflammatory skin of patients with chronic spontaneous urticaria in comparison to subjects with healthy skin. Fifty adult patients with chronic spontaneous urticaria and 23 skin-healthy subjects were studied. Chronic spontaneous urticaria was defined as recurrent weals for more than 6 weeks. Autologous serum skin test was performed in all patients with chronic spontaneous urticaria and BDNF serum levels were analysed by enzyme immunoassay in all subjects. Furthermore, skin biopsies were taken from weals of eight patients with chronic spontaneous urticaria as well as from healthy skin of eight controls to evaluate the expression of BDNF and its receptors including tyrosine kinase (trk) B and pan-neurotrophin receptor p75(NTR) by immunohistochemistry. BDNF serum levels were detectable in all subjects studied. However, BDNF levels were significantly higher in patients with chronic spontaneous urticaria compared to non-atopic skin-healthy controls (Pchronic spontaneous urticaria compared with controls (Pchronic spontaneous urticaria and controls and no difference in BDNF serum levels between autologous serum skin test-positive (n=23) and -negative (n=27) patients with chronic spontaneous urticaria. This study shows that BDNF is increased in serum and diseased skin of patients with chronic spontaneous urticaria, suggesting a role for neurotrophins in the pathophysiology of this chronic inflammatory skin disease. Further studies are needed to address the functional role of BDNF on key target effector cells in chronic spontaneous urticaria to establish new

  9. Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

    Directory of Open Access Journals (Sweden)

    Bin Tang

    Full Text Available B-cell leukemia/lymphoma 11B (Bcl11b is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.

  10. Association of Lipid Peroxidation and Brain-Derived Neurot