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Sample records for acid prevents dendritic

  1. Curcumin prevents human dendritic cell response to immune stimulants

    Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

    2012-01-01

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14+ monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing naïve CD4+ T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant. PMID:18639521

  2. Curcumin prevents human dendritic cell response to immune stimulants

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14+ monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4+ T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant

  3. Performance Evaluation of Stirrers for Preventing Dendrite Growth on Liquid Cathode

    An electrolytic system (zinc anode-gallium cathode) was setup to evaluate the performance of several stirrers prepared for this study, where stirrers have been used to prevent uranium from forming dendrite on the cathode in pyrochemical process. In the case of no-stirring condition, zinc dendrites began to grow on the gallium surface in 1 hour and some dendrite grew out of the cathode crucible around 6 hours. When a rectangular stirrer or a tilt stirrer was rotated, at 40150 rpm, to mix the liquid gallium cathode, dendritic growth of zinc metal was prevented irrespective of revolution speed, but some of the deposits overflowed out of the cathode crucible owing to the large centrifugal forces at 150 rpm. The harrow stirrer did not nearly retard the dendrite growth at 40 rpm, but the dendrite growth was retarded at higher than 100 rpm and the zinc deposits also did not overflow at 150 rpm. Pounder could also prevent the dendrite growth to some extent but it had some difficulties in operation compared with other types of stirrers.

  4. DMPD: Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 18641647 Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases... (.csml) Show Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases....iral infection andautoimmune diseases. Authors Gilliet M, Cao W, Liu YJ. Publication Nat Rev Immunol. 2008 A

  5. Distinct gut-derived lactic acid bacteria elicit divergent dendritic cell-mediated NK cell responses

    Fink, Lisbeth Nielsen; Zeuthen, Louise Hjerrild; Christensen, Hanne;

    2007-01-01

    Lactic acid bacteria (LAB) are abundant in the gastrointestinal tract where they continuously regulate the immune system. NK cells are potently activated by dendritic cells (DCs) matured by inflammatory stimuli, and NK cells are present in the gut epithelium and in mesenteric lymph nodes, but it is...

  6. Protocatechuic acid inhibits human dendritic cell functional activation: role of PPARγ up-modulation.

    Del Cornò, Manuela; Varano, Barbara; Scazzocchio, Beatrice; Filesi, Carmelina; Masella, Roberta; Gessani, Sandra

    2014-06-01

    Polyphenols have been shown to exhibit anti-inflammatory, anti-oxidant and immunomodulatory activities. However, the effects of anthocyanins, flavonoids of great nutritional interest, in particular of their metabolite protocatechuic acid (PCA) on the phenotypic and functional maturation of human dendritic cells (DCs) are still largely unknown. In this study, we report that PCA is efficiently taken up and accumulated in human monocyte-derived DCs (MD-DCs). PCA exposure of MD-DCs markedly impaired the production of proinflammatory cytokines and chemokines (i.e. IL-6, IL-8 and CCL2) in response to bacterial endotoxin and leptin, and down-regulated the lipopolysaccharide (LPS)-induced migratory response of MD-DCs to CCL19. Conversely, the phenotypic profile induced by LPS-mediated activation as well as IL-12 production was not affected. Interestingly, we found that PPARγ is a main factor in the PCA-induced effects as blocking its activity abolish PCA capacity to down-regulate IL-6 and IL-8, but not CCL2, secretion and to inhibit MD-DC migration. In keeping with this observation, cytosol to nucleus translocation and PPARγ activity were found to be directly stimulated by PCA exposure of MD-DCs. These novel findings provide new insight into the immunoregulatory effects of polyphenol metabolites in DCs opening new perspectives on their potential application in the prevention of acute and chronic inflammatory diseases. PMID:24576555

  7. Boric acid assisted electrosynthesis of hierarchical three-dimensional cobalt dendrites and microspheres

    Sivasubramanian, R. [Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036 India (India); Sangaranarayanan, M.V., E-mail: sangara@iitm.ac.in [Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036 India (India)

    2012-10-15

    The use of boric acid as the structure-directing agent and supporting electrolyte is shown to lead to a simple and robust strategy of obtaining hierarchical three dimensional cobalt dendrites, flower-like crystals and microspheres on stainless steel (SS) surfaces at room temperature. The phase and morphology of the dendrites are studied using Scanning Electron Microscopy (SEM), X-ray diffraction (XRD) and Energy Dispersive X-ray analysis (EDAX). The pre-dominant occurrence of cobalt(111) plane is noticed from XRD data while the magnetization studies using Vibrating Sample Magnetometer (VSM) provides a high coercivity value of {approx}574.6 Oe for cobalt dendrimers. The mechanism of formation of dendrimers is discussed using the classical Diffusion-Limited Aggregation (DLA) model. Highlights: Black-Right-Pointing-Pointer Preparation of cobalt dendrimers and microspheres using electrodeposition. Black-Right-Pointing-Pointer Boric acid acts as a structure directing agent and supporting electrolyte. Black-Right-Pointing-Pointer High coecivity values. Black-Right-Pointing-Pointer Formation of dendrites interpreted using the Diffusion-Limited Aggregation model.

  8. Dendrite Spacing Selection during Directional Solidification of Pivalic Acid-Ethanol System

    Myung-Jin Suk; Young-Min Park; Youn-Che Kim

    2008-01-01

    Unidirectional solidification of pivalic acid (PVA)-ethanol (Eth) mixture was performed to examine whether an allowable range of primary dendrite spacing definitely exists at a given growth velocity and how the range is history-dependent. PVA-0.59 wt pct Eth was unidirectionally solidified in the range of growth velocity 0.5-64 μm/s at the temperature gradient of 2.3 K/mm. Sequential change in growth velocity was imposed to determine the upper and lower limits for the allowable range of stable spacing. An allowable range of the steady state primary spacing was observed at a given growth velocity, and the extent of the range seems to be dependent on the degree to which step-increase or step-decrease in growth velocity is accomplished. As the degree of sequential change in growth velocity increases, the history-dependence of the selection for the primary dendrite spacing tends to disappear.

  9. The synergetic effect of lithium polysulfide and lithium nitrate to prevent lithium dendrite growth

    Li, Weiyang; Yao, Hongbin; Yan, Kai; Zheng, Guangyuan; Liang, Zheng; Chiang, Yet-Ming; Cui, Yi

    2014-01-01

    Lithium metal has shown great promise as an anode material for high-energy storage systems, owing to its high theoretical specific capacity and low negative electrochemical potential. Unfortunately, uncontrolled dendritic and mossy lithium growth, as well as electrolyte decomposition inherent in lithium metal-based batteries, cause safety issues and low Coulombic efficiency. Here we demonstrate that the growth of lithium dendrites can be suppressed by exploiting the reaction between lithium a...

  10. DMPD: The role of viral nucleic acid recognition in dendritic cells for innate andadaptive antiviral immunity. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 18086372 The role of viral nucleic acid recognition in dendritic cells for innate a...1-14. Epub 2007 Nov 9. (.png) (.svg) (.html) (.csml) Show The role of viral nucleic acid recognition in dend...ritic cells for innate andadaptive antiviral immunity. PubmedID 18086372 Title The

  11. Dendritic Assembly of Heteromeric γ-Aminobutyric Acid Type B Receptor Subunits in Hippocampal NeuronsS⃞

    Ramírez, Omar A.; Vidal, René L.; Tello, Judith A.; Vargas, Karina J.; Kindler, Stefan; Härtel, Steffen; Couve, Andrés

    2009-01-01

    Understanding the mechanisms that control synaptic efficacy through the availability of neurotransmitter receptors depends on uncovering their specific intracellular trafficking routes. γ-Aminobutyric acid type B (GABAB) receptors (GABABRs) are obligatory heteromers present at dendritic excitatory and inhibitory postsynaptic sites. It is unknown whether synthesis and assembly of GABABRs occur in the somatic endoplasmic reticulum (ER) followed by vesicular transport to ...

  12. Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice

    Sela, Uri; Olds, Peter; Park, Andrew; Schlesinger, Sarah J.; Steinman, Ralph M.

    2011-01-01

    Foxp3+ regulatory T cells (T reg cells) effectively suppress immunity, but it is not determined if antigen-induced T reg cells (iT reg cells) are able to persist under conditions of inflammation and to stably express the transcription factor Foxp3. We used spleen cells to stimulate the mixed leukocyte reaction (MLR) in the presence of transforming growth factor β (TGF-β) and retinoic acid. We found that the CD11chigh dendritic cell fraction was the most potent at inducing high numbers of allo...

  13. Electrodeposition of dendritic Pd nanoarchitectures on n-GaN(0001): nucleation and electrocatalysis for direct formic acid fuel cells

    Dendritic Pd nanoarchitectures were electrochemically deposited on single-crystal n-GaN(0001) by cyclic voltammetry and employed as anode electrocatalyst for direct formic acid fuel cells. The Pd deposition on n-GaN(0001) was found to commence at 0.2 V vs. Ag/AgCl without underpotential deposition process and follow the typical instantaneous nucleation in large overpotential region. High-resolution transmission electron microscope images revealed that numerous small branches were formed around the trunk of dendritic structures and grew along the <111> directions. The as-obtained dendritic Pd nanoarchitectures showed good catalytic performance for formic acid and the oxidation peak potential appeared at 0.45 V vs. Ag/AgCl. The maximum current density and mass activity were 19.7 mA cm−1 and 904 mA mg−1, respectively, for the dendritic Pd nanocrystals obtained by cycling the potentials from -0.25 to 1.0 V for 5 times

  14. Cellular glutathione prevents cytolethality of monomethylarsonic acid

    Inorganic arsenicals are clearly toxicants and carcinogens in humans. In mammals, including humans, inorganic arsenic often undergoes methylation, forming compounds such as monomethylarsonic acid (MMAsV) and dimethylarsinic acid (DMAsV). However, much less information is available on the in vitro toxic potential or mechanisms of these methylated arsenicals, especially MMAsV. We studied the molecular mechanisms of in vitro cytolethality of MMAsV using a rat liver epithelial cell line (TRL 1215). MMAsV was not cytotoxic in TRL 1215 cells even at concentrations exceeding 10 mM, but it became weakly cytotoxic and induced both necrotic and apoptotic cell death when cellular reduced glutathione (GSH) was depleted with the glutathione synthase inhibitor, L-buthionine-[S,R]-sulfoximine (BSO), or the glutathione reductase inhibitor, carmustine. Similar results were observed in the other mammalian cells, such as human skin TIG-112 cells, chimpanzee skin CRT-1609 cells, and mouse metallothionein (MT) positive and MT negative embryonic cells. Ethacrynic acid (EA), an inhibitor of glutathione S-transferase (GST) that catalyses GSH-substrate conjugation, also enhanced the cytolethality of MMAsV, but aminooxyacetic acid (AOAA), an inhibitor of β-lyase that catalyses the final breakdown of GSH-substrate conjugates, had no effect. Both the cellular GSH levels and the cellular GST activity were increased by the exposure to MMAsV in TRL 1215 cells. On the other hand, the addition of exogenous extracellular GSH enhanced the cytolethality of MMAsV, although cellular GSH levels actually prevented the cytolethality of combined MMAsV and exogenous GSH. These findings indicate that human arsenic metabolite MMAsV is not a highly toxic compound in mammalian cells, and the level of cellular GSH is critical to its eventual toxic effects

  15. Retinoic acid promotes the development of Arg1-expressing dendritic cells for the regulation of T-cell differentiation

    Chang, Jinsam; Thangamani, Shankar; Kim, Myung H.; Ulrich, Benjamin; Morris, Sidney M.; Chang H Kim

    2013-01-01

    Arginase I (Arg1), an enzyme expressed by many cell types including myeloid cells, can regulate immune responses. Expression of Arg1 in myeloid cells is regulated by a number of cytokines and tissue factors that influence cell development and activation. Retinoic acid, produced from vitamin A, regulates the homing and differentiation of lymphocytes and plays important roles in the regulation of immunity and immune tolerance. We report here that optimal expression of Arg1 in dendritic cells re...

  16. Heligmosomoides induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut Tcell responses

    Immunological diseases like inflammatory bowel disease (IBD) are infrequent in less developed countries possibly because helminths provide protection by modulating host immunity. In IBD murine models, the helminth Heligmosomoides bakeri (Hb) prevents colitis. It was determined if Hb mediated IBD pro...

  17. DOES JASMONIC ACID PREVENT THE GERMINATION

    ÇAVUŞOĞLU, Kürşat

    2009-01-01

    Abstract: Effect of jasmonic acid on seed germination and seedling growth of barley (Hordeum vulgare L. cv. Bülbül 89) was investigated in the present study. Jasmonic acid concentrations less than 1500 µM have not inhibited the seed germination, while 1500 and 2000 µM jasmonic acid levels caused atypical germination. The germination was completely inhibited at 3000 µM level of jasmonic acid. However, the seedling growth clearly slowed down with increasing concentrations of jasmonic acid. Furt...

  18. Effects of RAMEA-complexed polyunsaturated fatty acids on the response of human dendritic cells to inflammatory signals

    Éva Rajnavölgyi

    2014-12-01

    Full Text Available The n−3 fatty acids are not produced by mammals, although they are essential for hormone synthesis and maintenance of cell membrane structure and integrity. They have recently been shown to inhibit inflammatory reactions and also emerged as potential treatment options for inflammatory diseases, such as rheumatoid arthritis, asthma and inflammatory bowel diseases. Dendritic cells (DC play a central role in the regulation of both innate and adaptive immunity and upon inflammatory signals they produce various soluble factors among them cytokines and chemokines that act as inflammatory or regulatory mediators. In this study we monitored the effects of α-linoleic acid, eicosapentaenoic acid and docosahexaenoic acid solubilized in a dimethyl sulfoxide (DMSO/ethanol 1:1 mixture or as complexed by randomly methylated α-cyclodextrin (RAMEA on the inflammatory response of human monocyte-derived dendritic cells (moDC. The use of RAMEA for enhancing aqueous solubility of n−3 fatty acids has the unambiguous advantage over applying RAMEB (the β-cyclodextrin analog, since there is no interaction with cell membrane cholesterol. In vitro differentiated moDC were left untreated or were stimulated by bacterial lipopolysaccharide and polyinosinic:polycytidylic acid, mimicking bacterial and viral infections, respectively. The response of unstimulated and activated moDC to n−3 fatty acid treatment was tested by measuring the cell surface expression of CD1a used as a phenotypic and CD83 as an activation marker of inflammatory moDC differentiation and activation by using flow cytometry. Monocyte-derived DC activation was also monitored by the secretion level of the pro- and anti-inflammatory cytokines IL-1β, TNF-α, IL-6, IL-10 and IL-12, respectively. We found that RAMEA-complexed n−3 fatty acids reduced the expression of CD1a protein in both LPS and Poly(I:C stimulated moDC significantly, but most efficiently by eicosapentaenic acid, while no significant

  19. Folic acid and birth defect prevention

    ... of certain birth defects. These include spina bifida, anencephaly, and some heart defects. Experts recommend women who ... Women who have had a baby with a neural tube defect may need a higher dose of folic acid. ...

  20. The primary prevention of birth defects: Multivitamins or folic acid?

    2004-03-01

    Full Text Available Periconceptional use of folic acid alone or in multivitamin supplements is effective for the primary prevention of neural-tube defects. The Hungarian randomized and two-cohort controlled trials showed that periconceptional multivitamin supplementation can reduce the occurrence of some other structural birth defects, i.e. congenital abnormalities. These findings were supported by many, but not all observational studies. Recently there have been two main debated questions. The first one is whether the use of folic acid alone or folic acid-containing multivitamins is better. The second one is connected with the dilemma of whether high dose of folic acid (e.g. 5 mg might be better than a daily multivitamin with 0.4 – 0.8 mg of folic acid. Comparison of the pooled data of two Hungarian trials using a multivitamin containing 0.8 mg folic acid and the data of the Hungarian Case-Control Surveillance of Congenital Abnormalities using high dose of folic acid seemed to be appropriate to answer these questions. Multivitamins containing 0.4 – 0.8 mg of folic acid were more effective for the reduction of neural-tube defects than high dose of folic acid. Both multivitamins and folic acid can prevent some part of congenital cardiovascular malformations. Only multivitamins were able to reduce the prevalence at birth of obstructive defects of urinary tract, limb deficiencies and congenital pyloric stenosis. However, folic acid was effective in preventing some part of rectal/anal stenosis/atresia, and high dose of folic acid had effect in preventing some orofacial clefts. The findings are consistent that periconceptional multivitamin and folic acid supplementation reduce the overall occurrence of congenital abnormalities in addition to the demonstrated effect on neural-tube defects.

  1. The primary prevention of birth defects: Multivitamins or folic acid?

    Czeizel, Andrew E

    2004-01-01

    Periconceptional use of folic acid alone or in multivitamin supplements is effective for the primary prevention of neural-tube defects. The Hungarian randomized and two-cohort controlled trials showed that periconceptional multivitamin supplementation can reduce the occurrence of some other structural birth defects, i.e. congenital abnormalities. These findings were supported by many, but not all observational studies. Recently there have been two main debated questions. The first one is whether the use of folic acid alone or folic acid-containing multivitamins is better. The second one is connected with the dilemma of whether high dose of folic acid (e.g. 5 mg) might be better than a daily multivitamin with 0.4 - 0.8 mg of folic acid. Comparison of the pooled data of two Hungarian trials using a multivitamin containing 0.8 mg folic acid and the data of the Hungarian Case-Control Surveillance of Congenital Abnormalities using high dose of folic acid seemed to be appropriate to answer these questions. Multivitamins containing 0.4 - 0.8 mg of folic acid were more effective for the reduction of neural-tube defects than high dose of folic acid. Both multivitamins and folic acid can prevent some part of congenital cardiovascular malformations. Only multivitamins were able to reduce the prevalence at birth of obstructive defects of urinary tract, limb deficiencies and congenital pyloric stenosis. However, folic acid was effective in preventing some part of rectal/anal stenosis/atresia, and high dose of folic acid had effect in preventing some orofacial clefts. The findings are consistent that periconceptional multivitamin and folic acid supplementation reduce the overall occurrence of congenital abnormalities in addition to the demonstrated effect on neural-tube defects. PMID:15912190

  2. Investigation of cutaneous penetration properties of stearic acid loaded to dendritic core-multi-shell (CMS) nanocarriers.

    Lohan, S B; Icken, N; Teutloff, C; Saeidpour, S; Bittl, R; Lademann, J; Fleige, E; Haag, R; Haag, S F; Meinke, M C

    2016-03-30

    Dendritic core-multi shell (CMS) particles are polymer based systems consisting of a dendritic polar polyglycerol polymer core surrounded by a two-layer shell of nonpolar C18 alkyl chains and hydrophilic polyethylene glycol. Belonging to nanotransport systems (NTS) they allow the transport and storage of molecules with different chemical characters. Their amphipihilic character CMS-NTS permits good solubility in aqueous and organic solutions. We showed by multifrequency electron paramagnetic resonance (EPR) spectroscopy that spin-labeled 5-doxyl stearic acid (5DSA) can be loaded into the CMS-NTS. Furthermore, the release of 5DSA from the carrier into the stratum corneum of porcine skin was monitored ex vivo by EPR spectroscopy. Additionally, the penetration of the CMS-NTS into the skin was analyzed by fluorescence microscopy using indocarbocyanine (ICC) covalently bound to the nanocarrier. Thereby, no transport into the viable skin was observed, whereas the CMS-NTS had penetrated into the hair follicles down to a depth of 340μm±82μm. Thus, it could be shown that the combined application of fluorescence microscopy and multi-frequency EPR spectroscopy can be an efficient tool for investigating the loading of spin labeled drugs to nanocarrier systems, drug release and penetration into the skin as well as the localization of the NTS in the skin. PMID:26853315

  3. SURFACE MODIFICATION OF CaCO3 WITH DENDRITIC CARBOXYLIC ACIDS

    Zhao-xia Guo; Jian Yu

    2002-01-01

    Nanometer calcium carbonate was modified with Frechet type polyether dendrons bearing a COOH group at the focal point by a wet-coating technique in dichloromethane at room temperature. The interaction between CaCO3 and the dendritic modifier was proven by IR and mass spectroscopy of the modified CaCO3 after thorough extraction with dichloromethane. The amount of tightly bonded organic modifier was estimated by TGA. It was shown that the amount of bonded molecules decreased with increasing generation number due to the larger number of branches. Compared to unmodified CaCO3, the modified CaCO3 possess different dispersibility in water and in organic solvents.

  4. Preparation and characterization of ZnS/poly(acrylamide-co-acrylic acid) dendritical nanocomposites by γ-irradiation

    Zinc sulfide poly(acrylamide-co-acrylic acid) [ZnS/P(AM-co-AA)] nanocomposites with a dendritical structure were successfully prepared in one step by γ-irradiation technique in an aqueous system at room temperature and under ambient pressure. The results from X-ray powder diffraction (XRD) analysis and IR spectrum of the final product showed the formation of ZnS nanoparticles and the polymerization of monomers, respectively. The photoluminescence (PL) peak of the as-prepared product centered at 450 nm, which showed an obvious red shift compared with the ZnS bulk material. The presence of copolymer was considered to be the main reason that influenced the shape and photoluminescence property of the composite

  5. Prevention of spontaneous autoimmune diabetes in NOD mice by transferring in vitro antigen-pulsed syngeneic dendritic cells

    Papaccio, G; Nicoletti, F; Pisanti, F A; Bendtzen, K; Galdieri, M

    2000-01-01

    To evaluate the effect of antigen-pulsed dendritic cell (DC) transfer on the development of diabetes, 5-week-old female NOD mice received a single iv injection of splenic syngeneic DC from euglycemic NOD mice pulsed in vitro with human y globulin (HGG). Eleven of 12 mice were protected from the d...

  6. Dendritic cell-based immunotherapy induces transient clinical response in advanced rat fibrosarcoma - comparison with preventive anti-tumour vaccination

    Kučera, A.; Pýcha, K.; Pajer, Petr; Špíšek, R.; Škába, R.

    2009-01-01

    Roč. 55, č. 4 (2009), s. 119-125. ISSN 0015-5500 Institutional research plan: CEZ:AV0Z50520514 Keywords : dendritic cells * immunotherapy * cancer immunotherapy * chemotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.924, year: 2009

  7. Regulation of gene expression and subcellular protein distribution in MLO-Y4 osteocytic cells by lysophosphatidic acid: Relevance to dendrite outgrowth

    Waters, Katrina M.; Jon M Jacobs; Gritsenko, Marina A.; Karin, Norman J.

    2011-01-01

    Osteoblastic and osteocytic cells are highly responsive to the lipid growth factor lysophosphatidic acid (LPA) but the mechanisms by which LPA alters bone cell functions are largely unknown. A major effect of LPA on osteocytic cells is the stimulation of dendrite membrane outgrowth, a process that we predicted to require changes in gene expression and protein distribution. We employed DNA microarrays for global transcriptional profiling of MLO-Y4 osteocytic cells grown for 6 and 24 hours in t...

  8. Ionic networks derived from the protonation of dendritic amines with carboxylic acid end‐functionalized PEGs

    Gonzalez, Lidia; Skov, Anne Ladegaard; Hvilsted, Søren

    2013-01-01

    weights (Mn ∼ 250 and Mn ∼ 600) are reported. Likewise, an ionic network based on PPI G1 and a long αω‐dicarboxylic acid functionalized PEG (Mn ∼ 4800) were evaluated. Simpler ionic structures based on tris(2‐aminoethyl)amine or hexamethylene diamine and the short DiCOOH‐PEGs are also investigated. The...

  9. Hyaluronic Acid Binding Peptides Prevent Experimental Staphylococcal Wound Infection

    Zaleski, Kathleen J. ; Kolodka, Tadeusz; Cywes-Bentley, Colette; McLoughlin, Rachel M.; Mary L. Delaney; Charlton, Bernard T.; Johnson, Wendy; Tzianabos, Arthur O.

    2006-01-01

    Staphylococcus aureus is a major cause of surgical wound infections. The development of mechanisms of antimicrobial resistance by this and other bacterial pathogens has prompted the search for new approaches to treat infectious diseases. Hyaluronic acid binding peptides have been shown to modulate cellular trafficking during host responses and were assessed for their ability to treat and possibly prevent experimental surgical wound infections caused by S. aureus. Treatment with these peptides...

  10. The primary prevention of birth defects: Multivitamins or folic acid?

    Andrew E. Czeizel

    2004-01-01

    Periconceptional use of folic acid alone or in multivitamin supplements is effective for the primary prevention of neural-tube defects. The Hungarian randomized and two-cohort controlled trials showed that periconceptional multivitamin supplementation can reduce the occurrence of some other structural birth defects, i.e. congenital abnormalities. These findings were supported by many, but not all observational studies. Recently there have been two main debated questions. The first one is whet...

  11. Natural Killer Cells Are Activated by Lactic Acid Bacteria-Matured Dendritic Cells

    Fink, Lisbeth Nielsen; Christensen, Hanne Risager; Frøkiær, Hanne

    of certain lactic acid bacteria has been shown to increase in vivo NK cytotoxicity. Here, we investigated how human gut flora-derived lactobacilli affect NK cells in vitro, by measuring proliferation and IFN-gamma production of human NK cells upon bacterial stimulation. Human peripheral blood NK...... encounter of NK cells with lactic acid bacteria will affect NK cell activation. Such activation of NK cells may potentially skew an on-going or subsequent immune response towards a Th1 response.......Natural killer (NK) cells are cells of the non-specific immune system lysing altered self-cells. A non-cytolytic subset of NK cells may serve a regulatory role by secreting cytokines. Bacteria translocating across the gastrointestinal mucosa are presumed to gain access to NK cells, as consumption...

  12. Once-yearly zoledronic acid in hip fracture prevention

    Oddom Demontiero

    2009-03-01

    Full Text Available Oddom Demontiero, Gustavo DuqueAging Bone Research Program, Nepean Clinical School, University of Sydney, Penrith, NSW, Australia; Department of Geriatric Medicine, Nepean Hospital, Penrith, NSW, AustraliaAbstract: Osteoporosis is an escalating global problem. Hip fractures, the most catastrophic complication of osteoporosis, continue to cause significant mortality and morbidity despite increasing availability of effective preventative agents. Among these agents, oral bisphosphonates have been the first choice for the treatment and prevention of osteoporotic fractures. However, the use of oral bisphosphonates, especially in the older population, has been limited by their side effects and method of administration thus compromising their persistent use. The resultant low adherence by patients has undermined their full potential and has been associated with an increase in the incidence of fragility fractures. Recently, annual intravenous zoledronic acid (ZOL has been approved for osteoporosis. Randomized controlled trials have demonstrated ZOL to be safe, have good tolerability and produce significant effect on bone mass and microarchitecture. Adherence has also been shown to be better with ZOL. Furthermore two large trials firmly demonstrated significant anti-osteoporotic effect (-59% relative risk reduction of hip fractures and mortality benefit (28% reduction in mortality of ZOL in older persons with recent hip fractures. In this review, we report the current evidence on the use of ZOL for the prevention of hip fractures in the elderly. We also report the pharmacological characteristics and the advantages and disadvantages of ZOL in this particular group.Keywords: osteoporosis, zoledronic acid, hip fracture, elderly

  13. The effect of short-chain fatty acids on human monocyte-derived dendritic cells

    Nastasi, Claudia; Candela, Marco; Bonefeld, Charlotte Menné;

    2015-01-01

    negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly......The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood....... The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted...

  14. The effect of short-chain fatty acids on human monocyte-derived dendritic cells.

    Nastasi, Claudia; Candela, Marco; Bonefeld, Charlotte Menné; Geisler, Carsten; Hansen, Morten; Krejsgaard, Thorbjørn; Biagi, Elena; Andersen, Mads Hald; Brigidi, Patrizia; Ødum, Niels; Litman, Thomas; Woetmann, Anders

    2015-01-01

    The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood. The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly reduced the release of several pro-inflammatory chemokines including CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11. Additionally, butyrate and propionate inhibited the expression of lipopolysaccharide (LPS)-induced cytokines such as IL-6 and IL-12p40 showing a strong anti-inflammatory effect. This work illustrates that bacterial metabolites far from the site of their production can differentially modulate the inflammatory response and generally provides new insights into host-microbiome interactions. PMID:26541096

  15. Lactic Acid Bacteria Strains Exert Immunostimulatory Effect on H. pylori-Induced Dendritic Cells

    Małgorzata Wiese

    2015-01-01

    Full Text Available The aim of this study was to find out if selected lactic acid bacteria (LAB strains (antagonistic or nonantagonistic against H. pylori in vitro would differ in their abilities to modulate the DCs maturation profiles reflected by their phenotype and cytokine expression patterns. Methods. Monocyte-derived DCs maturation was elicited by their direct exposure to the LAB strains of L. rhamnosus 900 or L. paracasei 915 (antagonistic and nonantagonistic to H. pylori, resp., in the presence or absence of H. pylori strain cagA+. The DCs maturation profile was assessed on the basis of surface markers expression and cytokines production. Results. We observed that the LAB strains and the mixtures of LAB with H. pylori are able to induce mature DCs. At the same time, the L. paracasei 915 leads to high IL-10/IL-12p70 cytokine ratio, in contrast to L. rhamnosus 900. Conclusions. This study showed that the analyzed lactobacilli strains are more potent stimulators of DC maturation than H. pylori. Interestingly from the two chosen LAB strains the antagonistic to H. pylori-L. rhamnosus strain 900 has more proinflammatory and probably antibactericidal properties.

  16. Nucleic acid detection in the diagnosis and prevention of schistosomiasis.

    He, Ping; Song, Lan-Gui; Xie, Hui; Liang, Jin-Yi; Yuan, Dong-Ya; Wu, Zhong-Dao; Lv, Zhi-Yue

    2016-01-01

    Schistosomiasis is an important zoonotic parasitic disease that causes serious harms to humans and animals. Surveillance and diagnosis play key roles in schistosomiasis control, however, current techniques for surveillance and diagnosis of the disease have limitations. As genome data for parasites are increasing, novel techniques for detection incorporating nucleotide sequences are receiving widespread attention. These sensitive, specific, and rapid detection methods are particularly important in the diagnosis of low-grade and early infections, and may prove to have clinical significance. This paper reviews the progress of nucleic acid detection in the diagnosis and prevention of schistosomiasis, including such aspects as the selection of target genes, and development and application of nucleic acid detection methods. PMID:27025210

  17. Folic acid and primary prevention of birth defects.

    Taruscio, Domenica; Carbone, Pietro; Granata, Orietta; Baldi, Francesca; Mantovani, Alberto

    2011-01-01

    Birth defects (BDs) are an important public health problem, due to their overall incidence, occurring in 2-3% of live births in European Union. Neural tube defects (NTDs) are among major NTDs, due to their severity and relatively high incidence; in the meanwhile NTDs are also the most effectively preventable BDs to date. In particular, an adequate folic acid (FA) intake reduces both the occurrence and the recurrence of NTDs; FA is the synthetic form of folates, naturally occurring vitamins in a number of foods, especially vegetables. The daily intake of 0.4 mg of FA should be recommended to all women of childbearing age who plan to become pregnant. The Italian Network for Primary Prevention of BDs through FA Promotion has achieved a significant improvement in FA awareness and use in the periconceptional period. Nevertheless, primary prevention of BDs needs to make further progress; the Italian National Centre for Rare Diseases participates in european sureveillance of congenital anomalies (EUROCAT) Joint Action as coordinator of activities on the effectiveness of BDs prevention. Mandatory food fortification with FA has not been introduced in any European country. The health benefits of FA in reducing the risk of NTDs are undisputed; however mechanistic and animal studies suggest a relationship between high FA intakes and increased cancer promotion, while human studies are still inconsistent and inconclusive. A Working Group organized by the European Food Safety Authority pointed out significant uncertainties about fortification safety and the need for more studies; currently, FA intake from fortified foods and supplements should not exceed 1 mg/day in adults. In conclusion, based on up-to-date scientific evidence, the Italian Network strategy pivots on periconceptional supplementation integrated with promotion of healthy eating habits, support to health education, enhancing the role of women in managing life choices about their health and pregnancy and increasing

  18. Acid Sphingomyelinase Inhibition Prevents Hemolysis During Erythrocyte Storage

    Richard S. Hoehn

    2016-06-01

    Full Text Available Background/Aims: During storage, units of human red blood cells (pRBCs experience membrane destabilization and hemolysis which may cause harm to transfusion recipients. This study investigates whether inhibition of acid sphingomyelinase could stabilize erythrocyte membranes and prevent hemolysis during storage. Methods: Human and murine pRBCs were stored under standard blood banking conditions with and without the addition of amitriptyline, a known acid sphingomyelinase inhibitor. Hemoglobin was measured with an electronic hematology analyzer and flow cytometry was used to measure erythrocyte size, complexity, phosphatidylserine externalization, and band 3 protein expression. Results: Cell-free hemoglobin, a marker of hemolysis, increased during pRBC storage. Amitriptyline treatment decreased hemolysis in a dose-dependent manner. Standard pRBC storage led to loss of erythrocyte size and membrane complexity, increased phosphatidylserine externalization, and decreased band 3 protein integrity as determined by flow cytometry. Each of these changes was reduced by treatment with amitriptyline. Transfusion of amitriptyline-treated pRBCs resulted in decreased circulating free hemoglobin. Conclusion: Erythrocyte storage is associated with changes in cell size, complexity, membrane molecular composition, and increased hemolysis. Acid sphingomyelinase inhibition reduced these changes in a dose-dependent manner. Our data suggest a novel mechanism to attenuate the harmful effects after transfusion of aged blood products.

  19. Preventive and therapeutic effects of tranexamic acid on postpartum bleeding

    Samaneh Solltani

    2014-12-01

    Full Text Available Postpartum hemorrhage is among the leading causes of maternal mortality throughout the world. Severe blood loss contributes to  the increased blood transfusion risk with its concerned inherent adverse events and therefore increased rate of emergency re-operative interventions such as arterial ligation or hysterectomy. It also can lead to protracted anemia, particularly in low or median income countries. Extended application of antifibrinolytic agents such as tranexamic acid has been customary for long years to stop or reduce blood loss in postpartum period. However, there are not enough reliable evidence to approve the real efficacy of these drugs. In this brief and summary review, we pointed to a few conducted studies. The PubMed was searched for keyword including postpartum hemorrhage, tranexamic acid, cesarean section, vaginal delivery, and blood loss prevention. The articles with language other than English were excluded from our review.  We concluded that more convincing information is needed to determine the precise effects of tranexamic acid, and its benefits against adverse effects.

  20. Dibucaine mitigates spreading depolarization in human neocortical slices and prevents acute dendritic injury in the ischemic rodent neocortex.

    W Christopher Risher

    Full Text Available Spreading depolarizations that occur in patients with malignant stroke, subarachnoid/intracranial hemorrhage, and traumatic brain injury are known to facilitate neuronal damage in metabolically compromised brain tissue. The dramatic failure of brain ion homeostasis caused by propagating spreading depolarizations results in neuronal and astroglial swelling. In essence, swelling is the initial response and a sign of the acute neuronal injury that follows if energy deprivation is maintained. Choosing spreading depolarizations as a target for therapeutic intervention, we have used human brain slices and in vivo real-time two-photon laser scanning microscopy in the mouse neocortex to study potentially useful therapeutics against spreading depolarization-induced injury.We have shown that anoxic or terminal depolarization, a spreading depolarization wave ignited in the ischemic core where neurons cannot repolarize, can be evoked in human slices from pediatric brains during simulated ischemia induced by oxygen/glucose deprivation or by exposure to ouabain. Changes in light transmittance (LT tracked terminal depolarization in time and space. Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. Remarkably, the occurrence of ouabain-induced terminal depolarization was delayed at a concentration of 1 µM that preserves synaptic function. Moreover, in vivo two-photon imaging in the penumbra revealed that, though spreading depolarizations did still occur, spreading depolarization-induced dendritic injury was inhibited by dibucaine administered intravenously at 2.5 mg/kg in a mouse stroke model.Dibucaine mitigated the effects of spreading depolarization at a concentration that could be well-tolerated therapeutically. Hence, dibucaine is a promising candidate to protect the brain from ischemic injury with an approach that does not rely on

  1. The AMPA receptor subunit GluR1 regulates dendritic architecture of motor neurons

    Inglis, Fiona M.; Crockett, Richard; Korada, Sailaja; Abraham, Wickliffe C.; Hollmann, Michael; Kalb, Robert G.

    2002-01-01

    The morphology of the mature motor neuron dendritic arbor is determined by activity-dependent processes occurring during a critical period in early postnatal life. The abundance of the AMPA receptor subunit GluR1 in motor neurons is very high during this period and subsequently falls to a negligible level. To test the role of GluR1 in dendrite morphogenesis, we reintroduced GluR1 into rat motor neurons at the end of the critical period and quantitatively studied the effects on dendrite architecture. Two versions of GluR1 were studied that differed by the amino acid in the "Q/R" editing site. The amino acid occupying this site determines single-channel conductance, ionic permeability, and other essential electrophysiologic properties of the resulting receptor channels. We found large-scale remodeling of dendritic architectures in a manner depending on the amino acid occupying the Q/R editing site. Alterations in the distribution of dendritic arbor were not prevented by blocking NMDA receptors. These observations suggest that the expression of GluR1 in motor neurons modulates a component of the molecular substrate of activity-dependent dendrite morphogenesis. The control of these events relies on subunit-specific properties of AMPA receptors.

  2. Regulation of gene expression and subcellular protein distribution in MLO-Y4 osteocytic cells by lysophosphatidic acid: Relevance to dendrite outgrowth.

    Waters, Katrina M.; Jacobs, Jon M.; Gritsenko, Marina A.; Karin, Norman J.

    2011-02-26

    Osteoblastic and osteocytic cells are highly responsive to the lipid growth factor lysophosphatidic acid (LPA) but the mechanisms by which LPA alters bone cell functions are largely unknown. A major effect of LPA on osteocytic cells is the stimulation of dendrite membrane outgrowth, a process that we predicted to require changes in gene expression and protein distribution. We employed DNA microarrays for global transcriptional profiling of MLO-Y4 osteocytic cells grown for 6 and 24h in the presence or absence of LPA. We identified 932 transcripts that displayed statistically significant changes in abundance of at least 1.25-fold in response to LPA treatment. Gene ontology (GO) analysis revealed that the regulated gene products were linked to diverse cellular processes, including DNA repair, response to unfolded protein, ossification, protein-RNA complex assembly, and amine biosynthesis. Gene products associated with the regulation of actin microfilament dynamics displayed the most robust expression changes, and LPA-induced dendritogenesis in vitro was blocked by the stress fiber inhibitor cytochalasin D. Mass spectrometry-based proteomic analysis of MLO-Y4 cells revealed significant LPA-induced changes in the abundance of 284 proteins at 6h and 844 proteins at 24h. GO analysis of the proteomic data linked the effects of LPA to cell processes that control of protein distribution and membrane outgrowth, including protein localization, protein complex assembly, Golgi vesicle transport, cytoskeleton-dependent transport, and membrane invagination/endocytosis. Dendrites were isolated from LPA-treated MLO-Y4 cells and subjected to proteomic analysis to quantitatively assess the subcellular distribution of proteins. Sets of 129 and 36 proteins were enriched in the dendrite fraction as compared to whole cells after 6h and 24h of LPA exposure, respectively. Protein markers indicated that membranous organelles were largely excluded from the dendrites. Highly represented among

  3. Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells

    Ben Chung Lap Chan

    2015-09-01

    Full Text Available Atopic dermatitis (AD is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC culture model coupled with the high-speed counter-current chromatography (HSCCC, high pressure liquid chromatography (HPLC and Liquid Chromatography-Mass Spectrometry (LCMS analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL-12 p40 and the functional cluster of differentiation (CD surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC.

  4. Inhibition of fatty acid synthase prevents preadipocyte differentiation

    Inhibition of fatty acid synthase (FAS) reduces food intake in rodents. As adipose tissue expresses FAS, we sought to investigate the effect of reduced FAS activity on adipocyte differentiation. FAS activity was suppressed either pharmacologically or by siRNA during differentiation of 3T3-L1 cells. Cerulenin (10 μM), triclosan (50 μM), and C75 (50 μM) reduced dramatically visible lipid droplet accumulation, while incorporation of [1-14C]acetate into lipids was reduced by 75%, 70%, and 90%, respectively. Additionally, the substances reduced FAS, CEBPα, and PPARγ mRNA by up to 85% compared to that of control differentiated cells. Transient transfection with FAS siRNA suppressed FAS mRNA and FAS activity, and this was accompanied by reduction of CEBPα and PPARγ mRNA levels, and complete prevention of lipid accumulation. CD36, a late marker of differentiation, was also reduced. Together, these results suggest that FAS generated signals may be essential to support preadipocyte differentiation

  5. Hierarchical assembly of diphenylalanine into dendritic nanoarchitectures.

    Han, Tae Hee; Oh, Jun Kyun; Lee, Gyoung-Ja; Pyun, Su-Il; Kim, Sang Ouk

    2010-09-01

    Highly ordered, multi-dimensional dendritic nanoarchitectures were created via self-assembly of diphenylalanine from an acidic buffer solution. The self-similarity of dendritic structures was characterized by examining their fractal dimensions with the box-counting method. The fractal dimension was determined to be 1.7, which demonstrates the fractal dimension of structures generated by diffusion limited aggregation on a two-dimensional substrate surface. By confining the dendritic assembly of diphenylalanine within PDMS microchannels, the self-similar dendritic growth could be hierarchically directed to create linearly assembled nanoarchitectures. Our approach offers a novel pathway for creating and directing hierarchical nanoarchitecture from biomolecular assembly. PMID:20605423

  6. Attenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells

    VanHorn J

    2012-03-01

    Full Text Available Justin VanHorn1, Jeffrey D Altenburg1, Kevin A Harvey1, Zhidong Xu1, Richard J Kovacs2, Rafat A Siddiqui1,31Cellular Biochemistry Laboratory, Methodist Research Institute, Indianapolis, 2Krannert Institute of Cardiology, Indianapolis, 3Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USAAbstract: Niacin, also known as nicotinic acid, is an organic compound that has several cardio-beneficial effects. However, its use is limited due to the induction of a variable flushing response in most individuals. Flushing occurs from a niacin receptor mediated generation of prostaglandins from arachidonic acid metabolism. This study examined the ability of docosahexaenoic acid, eicosapentaenoic acid, and omega-3 polyunsaturated fatty acids (PUFAs, to attenuate niacin-induced prostaglandins in THP-1 macrophages. Niacin induced both PGD2 and PGE2 generation in a dose-dependent manner. Niacin also caused an increase in cytosolic calcium and activation of cytosolic phospholipase A2. The increase in PGD2 and PGE2 was reduced by both docosahexaenoic acid and eicosapentaenoic acid, but not by oleic acid. Omega-3 PUFAs efficiently incorporated into cellular phospholipids at the expense of arachidonic acid, whereas oleic acid incorporated to a higher extent but had no effect on arachidonic acid levels. Omega-3 PUFAs also reduced surface expression of GPR109A, a human niacin receptor. Furthermore, omega-3 PUFAs also inhibited the niacin-induced increase in cytosolic calcium. Niacin and/or omega-3 PUFAs minimally affected cyclooxygenase-1 activity and had no effect on cyclooxygenase -2 activity. The effects of niacin on PGD2 generation were further confirmed using Langerhans dendritic cells. Results of the present study indicate that omega-3 PUFAs reduced niacin-induced prostaglandins formation by diminishing the availability of their substrate, as well as reducing the surface expression of niacin receptors. In conclusion, this study

  7. Species Barrier Prevents an Abnormal Isoform of Prion Protein from Accumulating in Follicular Dendritic Cells of Mice with Creutzfeldt-Jakob Disease

    Muramoto, Tamaki; Kitamoto, Tetsuyuki; Hoque, Mohammad Zahirul; Tateishi, Jun; Goto, Ikuo

    1993-01-01

    The accumulation of abnormal prion protein in follicular dendritic cells did not occur in mice inoculated with materials from human Creutzfeldt-Jakob disease, whereas it always occurred in mice inoculated with mouse-adapted agents, suggesting an intense expression of the species barrier in the lymphoreticular system.

  8. Adding Folic Acid to Corn Masa Flour May Prevent Birth Defects

    ... For Consumers Consumer Updates Adding Folic Acid to Corn Masa Flour May Prevent Birth Defects Share Tweet ... mainstay of their regular diets—which often are corn masa-based.” This could be a reason why ...

  9. Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer

    Getino Redondo, María; Sanabria Ríos, David J.; Fernández López, Raúl; Campos Gómez, Javier; Sánchez López, José M.; Fernández Medarde, Antonio; Carballeira Cabranes, Néstor M.; Cruz Calahorra, Fernando de la

    2015-01-01

    Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic resistance genes among human pathogens. Antibiotic resistance spread could be halted or diminished by molecules that interfere with the conjugation process. In this work, synthetic 2-alkynoic fatty acids were identified as a novel class of conjugation inhibitors. Their chemical properties were investigated by using the prototype 2-hexadecynoic acid and its derivatives. Essential fe...

  10. α-Linolenic acid prevents endoplasmic reticulum stress-mediated apoptosis of stearic acid lipotoxicity on primary rat hepatocytes

    Shi Hongyang

    2011-05-01

    Full Text Available Abstract Aims Lipid accumulation in non-adipose tissues leads to cell dysfunction and apoptosis, a phenomenon known as lipotoxicity. Unsaturated fatty acids may offset the lipotoxicity associated with saturated fatty acids. Stearic acid induced endoplasmic reticulum (ER stress and caused apoptotic and necrotic cell death in the primary rat hepatocytes. Methods Cell viability was investigated using MTT assay, and apoptosis was evaluated with Hoechst 33342 staining. Western blot analysis was used to examine the changes in the expression levels of glucose regulated protein 78 (GRP78, glucose regulated protein 94 (GRP94, and C/EBP homologous protein (CHOP. Caspase-3 activity was evaluated using a Caspase-3 substrate kit. Results We have studied the ability of α-linolenic acid to prevent endoplasmic reticulum stress-mediated apoptosis of rat hepatocytes elicited by stearic acid and thapsigargin. Incubation of primary rat hepatocytes for 16 h with stearic acid produced a significant increase in cell death. Stearic acid also increased levels of three indicators of ER stress -- GRP78, CHOP, and GRP94. α-Linolenic acid distinctly reduced cell death and levels of all three indicators of ER stress brought about by stearic acid. Thapsigargin, which induces ER stress produced similar effects to those obtained using stearic acid; its effects were partly reversed by α-linolenic acid. Conclusion These results suggest that α-linolenic acid prevents ER stress-mediated apoptosis of stearic acid lipotoxicity on primary rat hepatocytes might become a target to develop new antiapoptotic compounds in nonalcoholic fatty liver disease (NAFLD.

  11. Preventive Effect of Phytic Acid on Isoproterenol-Induced Cardiotoxicity in Wistar Rats

    Brindha, E.; Rajasekapandiyan, M.

    2015-01-01

    This study was aimed to evaluate the preventive role of phytic acid on membrane bound enzymes such as sodium potassium- dependent adenosine triphosphatase (Na+ /K+ ATPase), calcium-dependent adenosine triphosphatase (Ca2+ ATPase) and magnesium- dependent adenosine triphosphatase (Mg2+ ATPase) and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with phytic acid (25 and 50...

  12. Preventive Effects of Zoledronic Acid on Bone Metastasis in Mice Injected with Human Breast Cancer Cells

    Jeong, Joon; Lee, Kyung Sun; Choi, Yang-Kyu; Oh, Young Ju; Lee, Hy-De

    2011-01-01

    Bisphosphonates are used routinely to reduce bone-related events in breast cancer patients with bone metastasis. We evaluated the effects of zoledronic acid, a third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice either simultaneously or after intracardiac injection of human breast cancer MDA-MB-231 cells. Nude mice treated with zoledronic acid at early time points showed a lower incid...

  13. Interleukin-22 binding protein (IL-22BP) is constitutively expressed by a subset of conventional dendritic cells and is strongly induced by retinoic acid.

    Martin, J C J; Bériou, G; Heslan, M; Chauvin, C; Utriainen, L; Aumeunier, A; Scott, C L; Mowat, A; Cerovic, V; Houston, S A; Leboeuf, M; Hubert, F X; Hémont, C; Merad, M; Milling, S; Josien, R

    2014-01-01

    Interleukin-22 (IL-22) is mainly produced at barrier surfaces by T cells and innate lymphoid cells and is crucial to maintain epithelial integrity. However, dysregulated IL-22 action leads to deleterious inflammation and is involved in diseases such as psoriasis, intestinal inflammation, and cancer. IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We show both in rats and mice that, in the steady state, the main source of IL-22BP is constituted by a subset of conventional dendritic cells (DCs) in lymphoid and non-lymphoid tissues. In mouse intestine, IL-22BP was specifically expressed in lamina propria CD103(+)CD11b(+) DC. In humans, IL-22BP was expressed in immature monocyte-derived DC and strongly induced by retinoic acid but dramatically reduced upon maturation. Our data suggest that a subset of immature DCs may actively participate in the regulation of IL-22 activity in the gut by producing high levels of IL-22BP. PMID:23653115

  14. Lactic Acid Bacteria Inducing a Weak Interleukin-12 and Tumor Necrosis Alpha Response in Human Dendritic Cells Inhibit Strongly Stimulating Lactic Acid Bacteria but Act Synergistically with Gram-Negative Bacteria

    Zeuthen, Louise Hjerrild; Christensen, Hanne Risager; Frøkiær, Hanne

    2006-01-01

    The development and maintenance of immune homeostasis indispensably depend on signals from the gut flora. Lactic acid bacteria (LAB), which are gram-positive (G+) organisms, are plausible significant players and have received much attention. Gram-negative (G-) commensals, such as members of the...... family Enterobacteriaceae, may, however, be immunomodulators that are as important as G+ organisms but tend to be overlooked. Dendritic cells (DCs) are crucial immune regulators, and therefore, the present study aimed at investigating differences among human gut flora-derived LAB and G- bacteria in their...... patterns of DC polarization. Human monocyte-derived DCs were exposed to UV-killed bacteria, and cytokine secretion and surface marker expression were analyzed. Profound differences in the DC polarization patterns were found among the strains. While strains of LAB varied greatly in their capacity to induce...

  15. Fatty acids in treatment and prevention of depression

    Wilczyńska, Agnieszka

    2013-01-01

    The increase of incident rates for depression and other psychiatric disorders is a serious threat for all communities.The study presents data verifying the relationship between the level of omega-3 PUFAs in the blood and an increased risk of depression, including the parallel standard therapy with antidepressants or not.There is an increasing number of evidences that fatty acids like DHA, AA and EPA are linked to depression. In epidemiological studies and clinical trials a correlation between...

  16. Conjugated linoleic acid (CLA) prevents age associated skeletal muscle loss

    Rahman, Md M.; Ganesh V. Halade; Jamali, Amina El; Fernandes, Gabriel

    2009-01-01

    In this study, we examined the effect of CLA isomers in preventing age-associated muscle loss and the mechanisms underlying this effect, using 12 months old C57BL/6 mice fed 10% corn oil (CO) or a diet supplemented with 0.5% c9t11-CLA, t10c12-CLA or c9t11-CLA+t10c12-CLA (CLA-mix) for 6 months. Both t10c12-CLA and CLA-mix groups showed significantly higher muscle mass, as compared to CO and c9t11-CLA groups, measured by dual-energy-Xray-absorptiometry and muscle wet weight. Enhanced mitochondr...

  17. Fatty acids in treatment and prevention of depression

    Wilczyńska, Agnieszka

    2013-07-01

    Full Text Available The increase of incident rates for depression and other psychiatric disorders is a serious threat for all communities.The study presents data verifying the relationship between the level of omega-3 PUFAs in the blood and an increased risk of depression, including the parallel standard therapy with antidepressants or not.There is an increasing number of evidences that fatty acids like DHA, AA and EPA are linked to depression. In epidemiological studies and clinical trials a correlation between the decline of omega-3 PUFA intake and an increasing risk for developing depression is considered.

  18. Spiraling eutectic dendrites

    Pusztai, Tamás; Rátkai, László; Szállás, Attila; Gránásy, László

    2013-01-01

    Eutectic dendrites forming in a model ternary system have been studied using the phase-field theory. The eutectic and one-phase dendrites have similar forms, and the tip radius scales with the interface free energy as for one-phase dendrites. The steady-state eutectic patterns appearing on these two-phase dendrites include concentric rings, and single- to multiarm spirals, of which the fluctuations choose, a stochastic phenomenon characterized by a peaked probability distribution. The number ...

  19. Nucleic Acid Drugs for Prevention of Cardiac Rejection

    Jun-ichi Suzuki

    2009-01-01

    Full Text Available Heart transplantation has been broadly performed in humans. However, occurrence of acute and chronic rejection has not yet been resolved. Several inflammatory factors, such as cytokines and adhesion molecules, enhance the rejection. The graft arterial disease (GAD, which is a type of chronic rejection, is characterized by intimal thickening comprised of proliferative smooth muscle cells. Specific treatments that target the attenuation of acute rejection and GAD formation have not been well studied in cardiac transplantation. Recent progress in the nucleic acid drugs, such as antisense oligodeoxynucleotides (ODNs to regulate the transcription of disease-related genes, has important roles in therapeutic applications. Transfection of cis-element double-stranded DNA, named as “decoy,” has been also reported to be a useful nucleic acid drug. This decoy strategy has been not only a useful method for the experimental studies of gene regulation but also a novel clinical strategy. In this paper, we reviewed the experimental results of NF-κB, E2F, AP-1, and STAT-1 decoy and other ODNs using the experimental heart transplant models.

  20. Role of n-3 series polyunsaturated fatty acids in cardiovascular disease prevention

    Lee AH

    2011-09-01

    Full Text Available Andy H Lee1, Naoko Hiramatsu21School of Public Health, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia; 2Laboratory of Nutritional Science, School of Human Science and Environment, University of Hyogo, Himeji, Hyogo, JapanAbstract: Cardiovascular disease is a major cause of morbidity and mortality worldwide. Its prevention through a healthy lifestyle and appropriate diet is important. Omega-3 polyunsaturated fatty acids (n-3 PUFA therapy has shown promise in both primary and secondary prevention of cardiovascular disease. This commentary discusses the nutritional role of n-3 PUFA, including its metabolism and physiological role, comparison with n-6 series PUFA, as well as complications due to deficiency. Clinical use of n-3 PUFA for the prevention and treatment of cardiovascular disease, recommended intake, and potential adverse effects will also be examined. The available scientific evidence suggests that its supplementation and clinical use ranging from 0.4 to 1 g/day can provide tangible benefits. However, further studies are required to determine optimal dosing and the relative ratio of docosahexaenoic acid and eicosapentaenoic acid that provides maximal cardioprotection and treatment of cardiovascular disease.Keywords: alpha-linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, cardiovascular disease, fish oil, polyunsaturated fatty acids

  1. Folic acid supplement use in the prevention of neural tube defects.

    Delany, C

    2011-01-01

    In 2008, planned folic acid fortification for the prevention of Neural Tube Defects (NTD) was postponed. Concurrently, the economic recession may have affected dietary folic acid intake, placing increased emphasis on supplement use. This study examined folic acid supplement use in 2009. A cross-sectional survey of 300 ante-natal women was undertaken to assess folic acid knowledge and use. Associations between demographic, obstetric variables and folic acid knowledge and use were examined. A majority, 284\\/297 (96%), had heard of folic acid, and 178\\/297 (60%) knew that it could prevent NTD. Most, 270\\/297 (91%) had taken it during their pregnancy, but only 107\\/297 (36%) had used it periconceptionally. Being older, married, planned pregnancy and better socioeconomic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from economic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from earlier years. Continuous promotion efforts are necessary. Close monitoring of folic acid intake and NTD rates is essential, particularly in the absence of fortification.

  2. Eicosapentaenoic Acid as long-term secondary prevention after ischemic stroke

    Nakase, Taizen; Sasaki, Masahiro; Suzuki, Akifumi

    2015-01-01

    Background It is sometimes difficult to choose anti-thrombotic agents for secondary prevention in stroke patients at high bleeding risk. Recently, Eicosapentaenoic Acid (EPA) was reported to reduce the recurrence of stroke in hypercholesterolemic patients without increasing hemorrhagic risk. In this study, we investigated the features of recurrent stroke patients during EPA medication as secondary stroke prevention. Methods Following the approval of the ethical committee, stroke patients in t...

  3. Tolerogenic dendritic cells induce antigen-specific hyporesponsiveness in insulin- and glutamic acid decarboxylase 65-autoreactive T lymphocytes from type 1 diabetic patients.

    Segovia-Gamboa, Norma; Rodríguez-Arellano, Martha Eunice; Rangel-Cruz, Rafael; Sánchez-Díaz, Moisés; Ramírez-Reyes, Julio César; Faradji, Raquel; González-Domínguez, Érika; Sánchez-Torres, Carmen

    2014-09-01

    Tolerogenic dendritic cells (tDC) constitute a promising therapy for autoimmune diseases, since they can anergize T lymphocytes recognizing self-antigens. Patients with type 1 diabetes mellitus (T1D) have autoreactive T cells against pancreatic islet antigens (insulin, glutamic acid decarboxylase 65 -GAD65-). We aimed to determine the ability of tDC derived from T1D patients to inactivate their insulin- and GAD65-reactive T cells. CD14+ monocytes and CD4+CD45RA- effector/memory lymphocytes were isolated from 25 patients. Monocyte-derived DC were generated in the absence (control, cDC) or presence of IL-10 and TGF-β1 (tDC), and loaded with insulin or GAD65. DC were cultured with T lymphocytes (primary culture), and cell proliferation and cytokine secretion were determined. These lymphocytes were rechallenged with insulin-, GAD65- or candidin-pulsed cDC (secondary culture) to assess whether tDC rendered T cells hyporesponsive to further stimulation. In the primary cultures, tDC induced significant lower lymphocyte proliferation and IL-2 and IFN-γ secretion than cDC; in contrast, tDC induced higher IL-10 production. Lymphocytes from 60% of patients proliferated specifically against insulin or GAD65 (group 1), whereas 40% did not (group 2). Most patients from group 1 had controlled glycemia. The secondary cultures showed tolerance induction to insulin or GAD65 in 14 and 10 patients, respectively. A high percentage of these patients (70-80%) belonged to group 1. Importantly, tDC induced antigen-specific T-cell hyporesponsiveness, since the responses against unrelated antigens were unaffected. These results suggest that tDC therapy against multiple antigens might be useful in a subset of T1D patients. PMID:24993292

  4. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    Brasky, Theodore M.; Till, Cathee; White, Emily; Neuhouser, Marian L; Song, Xiaoling; Goodman, Phyllis; Thompson, Ian M; King, Irena B.; Albanes, Demetrius; Kristal, Alan R.

    2011-01-01

    Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55–84 years, in the Prostate Cancer Prevention Trial during 1994–2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were ...

  5. Folic acid supplements to prevent neural tube defects: trends in East of Ireland 1996-2002.

    Ward, M

    2004-10-01

    Promotion of folic acid to prevent neural Tube Defects (NTD) has been ongoing for ten years in Ireland, without a concomitant reduction in the total birth prevalence of NTD. The effectiveness of folic acid promotion as the sole means of primary prevention of NTD is therefore questionable. We examined trends in folic acid knowledge and peri-conceptional use from 1996-2002 with the aim of assessing the value of this approach. From 1996-2002, 300 women attending ante-natal clinics in Dublin hospitals annually were surveyed regarding their knowledge and use of folic acid. During the period the proportion who had heard of folic acid rose from 54% to 94% between 1996 and 2002 (c2 test for trend: p<0.001). Knowledge that folic acid can prevent NTD also rose from 21% to 66% (c2 test for trend: p<0.001). Although the proportion who took folic acid during pregnancy increased from 14% to 83% from 1996 to 2002 (c2 test for trend: p<0.001), peri-conceptional intake did not rise above 24% in any year. There is a high awareness of folic acid and its relation to NTD, which is not matched by peri-conceptional uptake. The main barrier to peri-conceptional uptake is the lack of pregnancy planning. To date promotional campaigns appear to have been ineffective in reducing the prevalence of NTD in Ireland. Consequently, fortification of staple foodstuffs is the only practical and reliable means of primary prevention of NTD.

  6. Quality and quantity of the alkaline amendments needed to prevent acid mine drainage

    Control of acid mine drainage requires not only treatment of existing drainage but prevention of future acidic drainage. Waste rock exposed during coal mining and processing may contain up to 6% pyritic sulfur. These rocks may have little inherent neutralization capacity and appear to be very long lived acid generators. This paper summarizes recent research into the influence of additives to coal waste rock for the prevention of acidic mine drainage. Methods have been developed whereby additives can be evaluated using an extended acid-base accounting method and by Soxhlet extraction methods. The former method provides a means for gross determination of dose and the latter method provides some kinetic information on acid release. In addition to the evaluation of the effect of ameliorants on acidity, metal release has also been examined. Mass balances on sulfur, iron manganese and aluminum are used to discuss the nature of the treatment chemical reactions. The economics and efficacy of various treatment products (lime, combustion ash, kiln dust, and phosphate in particular) are discussed

  7. Salicylic acid: a link between aspirin, diet and the prevention of colorectal cancer.

    Paterson, J R; Lawrence, J R

    2001-08-01

    Aspirin was introduced into clinical practice more than 100 years ago. This unique drug belongs to a family of compounds called the salicylates, the simplest of which is salicylic acid, the principal metabolite of aspirin. Salicylic acid is responsible for the anti-inflammatory action of aspirin, and may cause the reduced risk of colorectal cancer observed in those who take aspirin. Yet salicylic acid and other salicylates occur naturally in fruits and plants, while diets rich in these are believed to reduce the risk of colorectal cancer. Serum salicylic acid concentrations are greater in vegetarians than non-vegetarians, and there is overlap between concentrations in vegetarians and those taking low-dose aspirin. We propose that the cancer-preventive action of aspirin is due to its principal metabolite, salicylic acid, and that dietary salicylates can have the same effect. It is also possible that natural salicylates contribute to the other recognized benefits of a healthy diet. PMID:11493722

  8. Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance

    Madsen, Lise; Guerre-Millo, Michéle; Flindt, Esben N;

    2002-01-01

    Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which potently regulates lipid homeostasis. Here we evaluate the ability of TTA to prevent diet-induced and genetically determined adiposity and insulin resistance. In Wistar rats fed a high fat diet, TTA administration...... completely prevented diet-induced insulin resistance and adiposity. In genetically obese Zucker (fa/fa) rats TTA treatment reduced the epididymal adipose tissue mass and improved insulin sensitivity. All three rodent peroxisome proliferator-activated receptor (PPAR) subtypes were activated by TTA in the...... ranking order PPARalpha > PPARdelta > PPARgamma. Expression of PPARgamma target genes in adipose tissue was unaffected by TTA treatment, whereas the hepatic expression of PPARalpha-responsive genes encoding enzymes involved in fatty acid uptake, transport, and oxidation was induced. This was accompanied...

  9. Interactions between prebiotics, probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention?

    Peluso, Ilaria; Romanelli, Luca; Palmery, Maura

    2014-05-01

    The metabolic syndrome can be prevented by the Mediterranean diet, characterized by fiber, omega-3 polyunsaturated fatty acids and polyphenols. However, the composition of the Mediterranean diet, which can be viewed as a natural multiple supplement, is poorly controlled, and its beneficial effects poorly predictable. The metabolic syndrome is associated with intestinal dysbiosis and the gut microbioma seems to be the main target and player in the interactions occurring between probiotics, prebiotics, omega 3 polyunsaturated fatty acids, and polyphenols. From the reviewed evidence, it is reasonable to manage growth and metabolism of gut microflora with specific prebiotics and polyphenols. Even though the healthy properties of functional foods and nutraceuticals still need to be fully elucidated, available data suggest that well-designed supplements, containing the better ratio of omega-3 polyunsaturated fatty acids and antioxidants, specific probiotic strains, and selected polyphenols and prebiotics, could be useful in metabolic syndrome prevention and treatment. PMID:24467635

  10. Acidic polyanion poly(acrylic acid) prevents calcium oxalate crystal deposition

    Kleinman, Jack G.; Alatalo, Laura J.; Beshensky, Ann M.; Wesson, Jeffrey A.

    2008-01-01

    Acidic macromolecules inhibit calcium oxalate nucleation, growth, aggregation and attachment to cells in vitro. To test for such an effect in vivo we used osmotic minipumps to continuously infuse several doses of the 5.1 kDa poly(acrylic acid) (pAA5.1) into rats fed a diet which causes renal calcium oxalate crystal deposition. Although kidneys of rats receiving the saline control contained calcium oxalate crystals, measured by polarized light microscopy, those of animals given pAA5.1 had sign...

  11. Eicosapentaenoic Acid Versus Docosahexaenoic Acid as Options for Vascular Risk Prevention: A Fish Story.

    Singh, Sarabjeet; Arora, Rohit R; Singh, Mukesh; Khosla, Sandeep

    2016-01-01

    Vascular inflammation is a key component involved in the process of arthrosclerosis, which in turn increases the risk for cardiovascular injury. In the last 10 years, there have been many trials that looked at omega-3 fatty acids as a way to reduce cardiovascular risk. These trials observed the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the traditional lipid panel and found that both EPA and DHA reduce triglyceride (TG) level and increase high-density lipoprotein cholesterol (HDL-C) levels but also increase the low-density lipoprotein cholesterol (LDL-C) levels. In the 2 more recent trials, the MARINE and ANCHOR, EPA was given as an adjunct therapy to high-risk patients and not only was the traditional lipids measured but also examined the vascular inflammatory biomarkers. The results of these 2 trials not only showed reduction in cardiovascular risk because of reduction in vascular inflammation and reduction in the lipid panel but also showed that one of the MARINE-derived omega-3 fatty acid is superior to the other. Data search for omega-3 fatty acids and cardiovascular risk was performed, and articles were selected for review from 2006 to date. The research studies were all double-blind randomized trials except for one, which was a single-blind and focused on the effects of omega-3 fatty acids on the entire lipid panel. The participants received DHA/EPA and compared with a placebo group on the effect seen in the lipid panel. The first 7 studies looked at the effects of omega-3 fatty acids on TG, LDL-C, and HDL-C; of the 7, 1 directly compared DHA and EPA, 2 focused on EPA, and 4 were directed towards DHA alone. The MARINE and ANCHOR trials were more recent and also looked at the same parameter but also monitored vascular inflammatory biomarkers and how they were affected by omega-3 fatty acids. A second data search was performed for vascular biomarkers and cardiovascular risk, and articles that focused on high-sensitivity C

  12. Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol

    Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in 51Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal 51Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol

  13. Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

    Hester M Den Ruijter

    2010-11-01

    Full Text Available Increased consumption of fatty fish, rich in omega-3 polyunsaturated fatty acids (3-PUFAs reduces the severity and number of arrhythmias. Long term 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating 3-PUFAs in the bloodstream and incorporated 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (3 or sunflower oil (9, as control for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch clamp technique in the absence and presence of acutely administered 3-PUFAs. Plasma of 3 fed rabbits contained more free eicosapentaenoic acid (EPA and isolated myocytes of 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA in their sarcolemma compared to control. In the absence of acutely administered fatty acids, 3 myocytes had a shorter action potential with a more negative plateau than 9 myocytes. In the 9 myocytes, but not in the 3 myocytes, acute administration of a mixture of EPA+DHA shortened the action potential significantly. From these data we conclude that incorporated 3-PUFAs into the sarcolemma and acutely administered 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac 3-PUFA status will probably not benefit from short term 3 supplementation as an antiarrhythmic therapy.

  14. Lithium Dendrite Suppression with UV-Curable Polysilsesquioxane Separator Binders.

    Na, Wonjun; Lee, Albert S; Lee, Jin Hong; Hwang, Seung Sang; Kim, Eunkyoung; Hong, Soon Man; Koo, Chong Min

    2016-05-25

    For the first time, an inorganic-organic hybrid polymer binder was used for the coating of hybrid composites on separators to enhance thermal stability and to prevent formation of lithium dendrite in lithium metal batteries. The fabricated hybrid-composite-coated separators exhibited minimal thermal shrinkage compared with the previous composite separators (separators revealed excellent C-rate and cyclability performance due to the prevention of lithium dendrite growth on the lithium anode even after 200 cycles under 0.2-5C (charge-discharge) conditions. The mechanism for lithium dendrite prevention was attributed to exceptional nanoscale surface mechanical properties of the hybrid composite coating layer compared with the lithium metal anode, as the elastic modulus of the hybrid-composite-coated separator far exceeded those of both the lithium metal anode and the required threshold for lithium metal dendrite prevention. PMID:27148625

  15. Effect of Tanshitone on prevention and treatment of retinoic acid-induced osteoporosis in mice

    ZHOU Yan-meng; LIU Yu-bo; GAO Yun-sheng

    2008-01-01

    Objective To observe the prevention and therapeutic effects of tanshitone (TAN) on retinoic acid induced osteoporosis in mice. Methods The mice osteoporosis was induced by given retinoic acid intragasttrically for two weeks. The histomorphological features of bone were observed and biochemical indexes in serum (Ca, P, ALP, TRAP, E2, BGP) were determined after mice were given TAN at the dose of 40, 80, 160 mg·kg-1 respectively. Results Tanshitone can induce high conversion of osteoporosis. The levels of P, ALP, TRAP and BGP in the TAN groups were lower than the model group, while the E2 level was higher than the model group. Conclusions Tanshitone can prevent the loss bone in the experimental mice. The mechanism may be that it improves the level of estrogenic hormone and inhibits the high bone turnover.

  16. Prevention of volatile fatty acids production and limitation of odours from winery wastewaters by denitrification.

    Bories, André; Guillot, Jean-Michel; Sire, Yannick; Couderc, Marie; Lemaire, Sophie-Andréa; Kreim, Virginie; Roux, Jean-Claude

    2007-07-01

    The effect of the addition of nitrate to winery wastewaters to control the formation of VFA in order to prevent odours during storage and treatment was studied in batch bioreactors at different NO(3)/chemical oxygen demand (COD) ratios and at full scale in natural evaporation ponds (2 x 7000 m(2)) by measuring olfactory intensity. In the absence of nitrate, butyric acid (2304 mgL(-1)), acetic acid (1633 mgL(-1)), propionic acid (1558 mgL(-1)), caproic acid (499 mgL(-1)) and valeric acid (298 mgL(-1)) were produced from reconstituted winery wastewater. For a ratio of NO(3)/COD=0.4 gg(-1), caproic and valeric acids were not formed. The production of butyric and propionic acids was reduced by 93.3% and 72.5%, respectively, at a ratio of NO(3)/COD=0.8, and by 97.4% and 100% at a ratio of NO(3)/COD=1.2 gg(-1). Nitrate delayed and decreased butyric acid formation in relation to the oxidoreduction potential. Studies in ponds showed that the addition of concentrated calcium nitrate (NITCAL) to winery wastewaters (3526 m(3)) in a ratio of NO(3)/COD=0.8 inhibited VFA production, with COD elimination (94%) and total nitrate degradation, and no final nitrite accumulation. On the contrary, in ponds not treated with nitrate, malodorous VFA (from propionic to heptanoïc acids) represented up to 60% of the COD. Olfactory intensity measurements in relation to the butanol scale of VFA solutions and the ponds revealed the pervasive role of VFA in the odour of the untreated pond as well as the clear decrease in the intensity and not unpleasant odour of the winery wastewater pond enriched in nitrates. The results obtained at full scale underscored the feasibility and safety of the calcium nitrate treatment as opposed to concentrated nitric acid. PMID:17467770

  17. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    Xu, Jintao; Eastman, Alison J.; Flaczyk, Adam; Neal, Lori M.; Zhao, Guolei; Carolan, Jacob; Malachowski, Antoni N.; Stolberg, Valerie R.; Yosri, Mohammed; Chensue, Stephen W.; Curtis, Jeffrey L.; Osterholzer, John J.

    2016-01-01

    ABSTRACT Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN) of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC) in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance. PMID:27406560

  18. Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis.

    Hatano, Yutaka; Man, Mao-Qiang; Uchida, Yoshikazu; Crumrine, Debra; Scharschmidt, Tiffany C; Kim, Esther G; Mauro, Theodora M; Feingold, Kenneth R; Elias, Peter M; Holleran, Walter M

    2009-07-01

    Neutralization of stratum corneum (SC) adversely impacts key epidermal functions, including permeability barrier homeostasis and SC integrity. Conversely, acidification of SC improves these functions in developmentally impaired (neonatal or aged) skin, and enhances function in normal skin. Hence, we hypothesized that acidification could alter the course of inflammatory dermatoses, which invariably exhibit an increased SC pH. Maintenance of a low pH by topical applications of the polyhydroxyl acid, lactobionic acid, during the repeated-challenge phase inhibited the development of oxazolone-induced atopic dermatitis (AD). Neither gross/histological dermatitis nor altered barrier function developed, and emergence of epidermal hyperplasia was prevented; however, cytokine generation decreased. Acidification also largely normalized the development of hapten-induced changes in eosinophil/mast cell densities, density of chemoattractant receptor-homologous molecule expressed on TH2-positive lymphocytes, and serum IgE levels. The pH-induced improvement in barrier function most likely accounts for the anti-inflammatory activity, which could be further attributed to normalization of both lamellar body secretion and lamellar bilayer formation. Acidification of SC alone substantially prevents development of barrier abnormalities and downstream immune abnormalities during the elicitation phase of murine AD. These results provide direct evidence for the "outside-inside" pathogenesis of AD and further suggest that maintenance of an acidic SC pH could prevent the emergence of AD in humans. PMID:19177139

  19. Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes

    Ramesh C. Gupta

    2008-03-01

    Full Text Available DNA damage is a pre-requisite for the initiation of cancer and agents that reduce this damage are useful in cancer prevention. In this study, we evaluated the ability of whole berries and berry phytochemical, ellagic acid to reduce endogenous oxidative DNA damage. Ellagic acid was selected based on > 95% inhibition of 8-oxodeoxyguosine (8-oxodG and other unidentified oxidative DNA adducts induced by 4-hydroxy-17B;-estradiol and CuCl2 in vitro. Inhibition of the latter occurred at lower concentrations (10 u(microM than that for 8-oxodG (100 u(microM. In the in vivo study, female CD-1 mice (n=6 were fed either a control diet or diet supplemented with ellagic acid (400 ppm and dehydrated berries (5% w/w with varying ellagic acid contents -- blueberry (low, strawberry (medium and red raspberry (high, for 3 weeks. Blueberry and strawberry diets showed moderate reductions in endogenous DNA adducts (25%. However, both red raspberry and ellagic acid diets showed a significant reduction of 59% (p < 0.001 and 48% (p < 0.01, respectively. Both diets also resulted in a 3-8 fold over-expression of genes involved in DNA repair such as xeroderma pigmentosum group A complementing protein (XPA, DNA excision repair protein (ERCC5 and DNA ligase III (DNL3. These results suggest that red raspberry and ellagic acid reduce endogenous oxidative DNA damage by mechanisms which may involve increase in DNA repair.

  20. Prevention of neural tube defects with folic acid: The Chinese experience.

    Ren, Ai-Guo

    2015-08-01

    Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28(th) day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a post-program survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs. PMID:26261765

  1. Prevention

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  2. Random fractal dendrites

    Croydon, David (David Alexander); Hambly, Ben M.; Dr. Ben Hambly

    2006-01-01

    Dendrites are tree-like topological spaces, and in this thesis, the physical characteristics of various random fractal versions of this type of set are investigated. This work will contribute to the development of analysis on fractals, an area which has grown considerably over the last twenty years. First, a collection of random self-similar dendrites is constructed, and their Hausdorff dimension is calculated. Previous results determining this quantity for random self-simi...

  3. Uninterrupted galvanic reaction for scalable and rapid synthesis of metallic and bimetallic sponges/dendrites as efficient catalysts for 4-nitrophenol reduction.

    Barman, Barun Kumar; Nanda, Karuna Kar

    2015-03-01

    Here, we demonstrate an uninterrupted galvanic replacement reaction (GRR) for the synthesis of metallic (Ag, Cu and Sn) and bimetallic (Cu-M, M=Ag, Au, Pt and Pd) sponges/dendrites by sacrificing the low reduction potential metals (Mg in our case) in acidic medium. The acidic medium prevents the oxide formation on Mg surface and facilitates the uninterrupted reaction. The morphology of dendritic/spongy structures is controlled by the volume of acid used for this reaction. The growth mechanism of the spongy/dendritic microstructures is explained by diffusion-limited aggregate model (DLA), which is also largely affected by the volume of acid. The significance of this method is that the yield can be easily predicted, which is a major challenge for the commercialization of the products. Furthermore, the synthesis is complete in 1-2 minutes at room temperature. We show that the sponges/dendrites efficiently act as catalysts to reduce 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) using NaBH4-a widely studied conversion process. PMID:25628256

  4. Radioresistance of dendritic cells

    To evaluate radiation sensitivity of dendritic cells in comparison with lymphocytes. T lymphocytes captured from peripheral blood were irradiated by 0 Gy, 10 Gy, 30 Gy. Apoptosis was measured by flowcytometry for staining of annexin V 4 hours after irradiation. Immature and mature dendritic cells processed from blood hematopoietic stem cell were irradiated by 0 Gy, 10 Gy, 30 Gy, 100 Gy respectively and apoptosis was measured by flowcytometry with time differences as 4h, 24h and 48h after irradiation. Morphometric analysis by percent nucleus was measured in three cell groups, also. Lymphocytes showed radiation sensitivity by increasing apoptotic fraction according to radiation dose. However, both mature and immature dendritic cells showed consistent fraction of apoptosis in spite of increasing radiation dose. Percent nucleus ratio is significantly higher in lymphocytes than that of mature or immature dendritic cells. Stimulation of T-cell by dendritic cells was not changed after irradiation. Dendritic cells showed radioresistance which was associated with small size of nucleus in comparison with lymphocytes and this result would be used as a basal data of radio-labelling for the cellular trafficking studies in nuclear medicine fields

  5. Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

    Bogin Vladimir

    2011-03-01

    Full Text Available Abstract The history of ascorbic acid (AA and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS and multi organ failure (MOF, has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a maintaining endothelial and suppression of inflammatory markers; b protection from sepsis in animal models; and c direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis.

  6. The potential role of boswellic acids in cancer prevention and treatment.

    Roy, Nand Kishor; Deka, Anindita; Bordoloi, Devivasha; Mishra, Srishti; Kumar, Alan Prem; Sethi, Gautam; Kunnumakkara, Ajaikumar B

    2016-07-10

    Despite the extensive research carried out in the field of cancer therapeutics, cancer is one of the most dreadful diseases in the world with no definitive treatment to date. The key attributes responsible for this are the various limiting factors associated with conventional chemotherapeutics that primarily include adverse side-effects and development of chemoresistance. Hence, there is an utter need to find compounds that are highly safe and efficacious for the prevention and treatment of cancer. Boswellic acid, a group of pentacyclic compounds, seems to be promising enough due to its inherent anti-cancerous properties. Considering this perspective, the present review highlights the established studies related to the anti-cancer potential of boswellic acid against different cancer types. The molecular mechanisms underlying the targets of boswellic acid that are accountable for its potent anti-cancer effect are also discussed. Overall, this review projects the pieces of evidence that reveal the potential of boswellic acid as a suitable candidate that can be appropriately developed and designed into a promising anti-cancer drug. PMID:27091399

  7. Antimicrobial activity of transition metal acid MoO3 prevents microbial growth on material surfaces

    Serious infectious complications of patients in healthcare settings are often transmitted by materials and devices colonised by microorganisms (nosocomial infections). Current strategies to generate material surfaces with an antimicrobial activity suffer from the consumption of the antimicrobial agent and emerging multidrug-resistant pathogens amongst others. Consequently, materials surfaces exhibiting a permanent antimicrobial activity without the risk of generating resistant microorganisms are desirable. This publication reports on the extraordinary efficient antimicrobial properties of transition metal acids such as molybdic acid (H2MoO4), which is based on molybdenum trioxide (MoO3). The modification of various materials (e.g. polymers, metals) with MoO3 particles or sol–gel derived coatings showed that the modified materials surfaces were practically free of microorganisms six hours after contamination with infectious agents. The antimicrobial activity is based on the formation of an acidic surface deteriorating cell growth and proliferation. The application of transition metal acids as antimicrobial surface agents is an innovative approach to prevent the dissemination of microorganisms in healthcare units and public environments. Highlights: ► The presented modifications of materials surfaces with MoO3 are non-cytotoxic and decrease biofilm growth and bacteria transmission. ► The material is insensitive towards emerging resistances of bacteria. ► Strong potential to reduce spreading of infectious agents on inanimate surfaces.

  8. Investigating Ascorbic Acid Effect in Prevention of CIN in Diabetic Patients

    Nough

    2013-06-01

    Full Text Available Introduction: Contrast induced nephropathy (CIN is one the complications resulting from coronary catheterization and is regarded as one of the reasons of acute kidney failure. Therefore, this study aimed to investigate the effect of ascorbic acid in the prevention of CIN in Yazd in 2012. Methods: This study involves a double blind clinical trial in which 90 Diabetic patients with coronary catheterization have attended. The patients were divided randomly into two groups: control group and treatment group. Demographic and clinical data were collected by a questionnaire. Treatment group received vitamin C (2 grams 2 hours before the intervention and the control groups were given 2 grams of the Placebo. The GFR (Glomerular filtration rate, BUN (Blood Urea Nitrogen, and Cr (Creatinin were measured and compared after 2-3 days. Results: The CIN in treatment group was about 3 patients (7.7% and was 7 (16.7% in the control group. Thus, no significant difference was observed; though, there was a significant difference between Cr and GFR before and after the treatment in vitamin C group (PV= 0.006, PV=0.001, but these differences were not significant in the placebo group.(PV=0.661, PV=0.747. Moreover, considering the participants’ age, sex and their primary function of kidney, a significant difference had not appeared due to the incidence of CIN between the two groups. Conclusion: Our study did not show Ascorbic Acid effects in prevention of CIN in Diabetic patients.

  9. EFFICACY OF ZOLEDRONIC ACID IN THE PREVENTION OF BONE METASTASES IN PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER

    T. N. Musaev

    2014-07-01

    Full Text Available The analysis of the performed study has established that zoledronic acid is an effective agent in multimodality therapy for locally advanced prostate cancer (PC and allows long-term stabilization of bone tissue. In addition, there is evidence for the efficacy of zoledronic acid in preventing bone metastases (BM and increasing the time to the first BM. The currently accumulated experience with zoledronic acid used in PC permits one to consider its use as standard concomitant therapy.

  10. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E; Redhi, Godfrey H; Panlilio, Leigh V; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R

    2013-11-01

    In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  11. Omega-3 fatty acid oxidation products prevent vascular endothelial cell activation by coplanar polychlorinated biphenyls

    Coplanar polychlorinated biphenyls (PCBs) may facilitate development of atherosclerosis by stimulating pro-inflammatory pathways in the vascular endothelium. Nutrition, including fish oil-derived long-chain omega-3 fatty acids, such as docosahexaenoic acid (DHA, 22:6ω-3), can reduce inflammation and thus the risk of atherosclerosis. We tested the hypothesis that cyclopentenone metabolites produced by oxidation of DHA can protect against PCB-induced endothelial cell dysfunction. Oxidized DHA (oxDHA) was prepared by incubation of the fatty acid with the free radical generator 2,2-azo-bis(2-amidinopropane) dihydrochloride (AAPH). Cellular pretreatment with oxDHA prevented production of superoxide induced by PCB77, and subsequent activation of nuclear factor-κB (NF-κB). A4/J4-neuroprostanes (NPs) were identified and quantitated using HPLC ESI tandem mass spectrometry. Levels of these NPs were markedly increased after DHA oxidation with AAPH. The protective actions of oxDHA were reversed by treatment with sodium borohydride (NaBH4), which concurrently abrogated A4/J4-NP formation. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) by PCB77 was markedly reduced by oxDHA, but not by un-oxidized DHA. These protective effects were proportional to the abundance of A4/J4 NPs in the oxidized DHA sample. Treatment of cells with oxidized eicosapentaenoic acid (EPA, 20:5ω-3) also reduced MCP-1 expression, but less than oxDHA. Treatment with DHA-derived cyclopentenones also increased DNA binding of NF-E2-related factor-2 (Nrf2) and downstream expression of NAD(P)H:quinone oxidoreductase (NQO1), similarly to the Nrf-2 activator sulforaphane. Furthermore, sulforaphane prevented PCB77-induced MCP-1 expression, suggesting that activation of Nrf-2 mediates the observed protection against PCB77 toxicity. Our data implicate A4/J4-NPs as mediators of omega-3 fatty acid-mediated protection against the endothelial toxicity of coplanar PCBs.

  12. Dietary n-3 long chain polyunsaturated fatty acids in allergy prevention and asthma treatment.

    Willemsen, Linette E M

    2016-08-15

    The rise in non-communicable diseases, such as allergies, in westernized countries links to changes in lifestyle and diet. N-3 long chain polyunsaturated fatty acids (LCPUFA) present in marine oils facilitate a favorable milieu for immune maturation and may contribute to allergy prevention. N-3 LCPUFA can suppress innate and adaptive immune activation and induce epigenetic changes. Murine studies convincingly show protective effects of fish oil, a source of n-3 LCPUFA, in food allergy and asthma models. Observational studies in human indicate that high dietary intake of n-3 LCPUFA and low intake of n-6 PUFA may protect against the development of allergic disease early in life. High n-6 PUFA intake is also associated with an increased asthma risk while n-3 LCPUFA may be protective and reduce symptoms. The quality of the marine oil used has impact on efficacy of allergy prevention and several observations link in particular n-3 LCPUFA DHA to allergy suppression. Randomized controlled trials indicate that optimal timing, duration and dosage of n-3 LC-PUFA is required to exert an allergy protective effect. Supplementation during early pregnancy and lactation has shown promising results regarding allergy prevention. However these findings should be confirmed in a larger cohort. Although clinical trials in asthma patients reveal no consistent clinical benefits of n-3 LCPUFA supplementation on lung function, it can suppress airway inflammation. Future food-pharma approaches may reveal whether adjunct therapy with dietary n-3 LCPUFA can improve allergy prevention or immunotherapy via support of allergen specific oral tolerance induction or contribute to the efficacy of drug therapy for asthma patients. PMID:27041644

  13. Dendritic Polymers for Theranostics

    Ma, Yuan; Mou, Quanbing; Wang, Dali; Zhu, Xinyuan; Yan, Deyue

    2016-01-01

    Dendritic polymers are highly branched polymers with controllable structures, which possess a large population of terminal functional groups, low solution or melt viscosity, and good solubility. Their size, degree of branching and functionality can be adjusted and controlled through the synthetic procedures. These tunable structures correspond to application-related properties, such as biodegradability, biocompatibility, stimuli-responsiveness and self-assembly ability, which are the key points for theranostic applications, including chemotherapeutic theranostics, biotherapeutic theranostics, phototherapeutic theranostics, radiotherapeutic theranostics and combined therapeutic theranostics. Up to now, significant progress has been made for the dendritic polymers in solving some of the fundamental and technical questions toward their theranostic applications. In this review, we briefly summarize how to control the structures of dendritic polymers, the theranostics-related properties derived from their structures and their theranostics-related applications.

  14. Preventive and curative effects of dicaffeoylquinic acid on early pulmonary fibrosis in mice

    Objective: To explore the effect of dicaffeoylquinic acid (IBE5) on prevention and treatment of pulmonary fibrosis induced by bleomycin (BLM) in mice and its mechanism. Methods: Hydroxyproline content determination, imaging analysis, collagen I and III assay, α-smooth muscle actin (α-SMA) and matrix metalloproteinase 7 (MMP-7 ) immunohistochemistry were performed. Results: 1)Hydroxyproline content decreased in fibrotic lung tissue after administration of IBE5(P<0.05). 2)The number of pulmonary alveoli reduced, alveolus interstitium was thickened and collagen deposition and fibrosis were formed in lung tissue of BLM group. The break of pulmonary alveoli and extension of pulmonary fibrosis were decreased by use of IBE5 (P<0.05). 3)A lot of collagen I and III were synthesized in lung interstitium in BLM group and their quantity was reduced in IBE5 group (P<0.05). 4) In BLM group, α-SMA expression increased and located in myofibroblasts in fibrotic area, and MMP7 immunohistochemical signal was located in myofibroblasts also. They were decreased in IBE5 group(P<0.05). Conclusion: IBE5 plays a preventive and curative role in pulmonary fibrosis by inhibition of transformation of fibroblasts towards myofibroblasts and MMP7 expression. (authors)

  15. Protocatechuic acid and human disease prevention: biological activities and molecular mechanisms.

    Masella, R; Santangelo, C; D'Archivio, M; Li Volti, G; Giovannini, C; Galvano, F

    2012-01-01

    Epidemiological evidence has shown that a high dietary intake of vegetables and fruit rich in polyphenols is associated with a reduction of cancer incidence and mortality from coronary heart disease. The healthy effects associated with polyphenol consumption have made the study of the mechanisms of action a matter of great importance. In particular, the hydroxybenzoic acid protocatechuic acid (PCA) has been eliciting a growing interest for several reasons. Firstly, PCA is one of the main metabolites of complex polyphenols such as anthocyanins and procyanidins that are normally found at high concentrations in vegetables and fruit, and are absorbed by animals and humans. Since the daily intake of anthocyanins has been estimated to be much higher than that of other polyphenols, the nutritional value of PCA is increasingly recognized. Secondly, a growing body of evidence supports the concept that PCA can exert a variety of biological effects by acting on different molecular targets. It has been shown that PCA possesses antioxidant, anti-inflammatory as well as antihyperglycemic and neuroprotective activities. Furthermore, PCA seems to have chemopreventive potential because it inhibits the in vitro chemical carcinogenesis and exerts pro-apoptotic and anti-proliferative effects in different tissues. This review is aimed at providing an up-dated and comprehensive report on PCA giving a special emphasis on its biological activities and the molecular mechanisms of action most likely responsible for a beneficial role in human disease prevention. PMID:22519395

  16. Modification of dendritic development.

    Feria-Velasco, Alfredo; del Angel, Alma Rosa; Gonzalez-Burgos, Ignacio

    2002-01-01

    Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the

  17. Preventing Food Allergies by Tricking Dendritic Cells

    Food allergies are adverse responses to components (usually proteins) within the foods we eat, which result in a self-damaging response from our immune system. A myriad of cellular and molecular components are involved in the decision to tolerate or respond to foreign molecules that pass through the...

  18. Treatments of free fatty acids to prevent or decrease colour fixation in cottonseed oil

    Helmy, H. E.

    1994-12-01

    Full Text Available Some treatments have been investigated to prevent or remove colour fixation of cottonseed oil containing high level of free fatty acids without using excess of sodium hydroxide in the refining step. The treatments included use of sodium carbonate and ethanolamine before and after subjecting a crude cottonseed oil containing excess of free fatty acid to a colour fixation treatment.
    The results revealed that the carbonate/ethanolamine treatment improved the oil colour by decreasing the free fatty acids and gossypol in the oil, without using any excess of sodium hydroxide.
    Carrying out the carbonate/ethanolamine treatment on cottonseed oil with high levels of free fatty acid before colour fixation takes place is more recommended than carrying out the same treatment on the same oil after it has been fixed.

    Se han investigado algunos tratamientos para prevenir o eliminar la fijación del color de aceite de semilla de algodón que contienen alto nivel de ácidos grasos libres, sin utilizar un exceso de hidróxido sódico en la etapa de refinación.
    Los tratamientos incluyeron el uso de carbonato sódico y etanolamina antes y después, sometiendo un aceite crudo de semilla de algodón que contiene exceso de ácidos grasos libres a tratamiento de fijación del color.
    Los resultados mostraron que el tratamiento carbonato/etanolamina mejoró el color del aceite por disminución de los ácidos grasos libres y gosipol en el aceite, sin utilizar un exceso de hidróxido sódico.
    Llevar a cabo el tratamiento con carbonato/etanolamina sobre aceite de semilla de algodón con niveles altos de ácidos grasos libres antes que tenga lugar la fijación del color es más recomendable que llevar a cabo el mismo tratamiento sobre el mismo aceite después de que se haya fijado.

  19. Role and significance of polyunsaturated fatty acids in nutrition in prevention and treatment of atherosclerosis

    Ristić Vanja I.; Ristić Gordana N.

    2003-01-01

    Introduction Hyperlipoproteinemia is a key factor in development of atherosclerosis, whereas regression of atherosclerosis mostly depends on decreasing the plasma level of total and LDL-cholesterol. Many studies have reported the hypocholesterolemic effect of linolenic acid. Types of polyunsaturated fatty acids (PUFA) Linoleic and α-linolenic acids are essential fatty acids. The main sources of linoleic acid are vegetable seeds and of α-linolenic acid - green parts of plants. α-linolenic acid...

  20. Alloy substantially free of dendrites and method of forming the same

    de Figueredo, Anacleto M.; Apelian, Diran; Findon, Matt M.; Saddock, Nicholas

    2009-04-07

    Described herein are alloys substantially free of dendrites. A method includes forming an alloy substantially free of dendrites. A superheated alloy is cooled to form a nucleated alloy. The temperature of the nucleated alloy is controlled to prevent the nuclei from melting. The nucleated alloy is mixed to distribute the nuclei throughout the alloy. The nucleated alloy is cooled with nuclei distributed throughout.

  1. Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.

    Tzu-Yu Lin

    Full Text Available An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L. Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+ concentration ([Ca(2+]C in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker known as ω-conotoxin MVIIC. In a kainic acid (KA rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+ entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.

  2. Eicosapentaenoic acid prevents high fat diet-induced metabolic disorders: Genomic and metabolomic analyses of underlying mechanism

    Previously our lab demonstrated eicosapenaenoic acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity by decreasing insulin resistance, glucose intolerance and inflammation. In the current study, we used genomic and metabolomic approaches to further investigate the molecular basis for t...

  3. Magnetic and dendritic catalysts.

    Wang, Dong; Deraedt, Christophe; Ruiz, Jaime; Astruc, Didier

    2015-07-21

    The recovery and reuse of catalysts is a major challenge in the development of sustainable chemical processes. Two methods at the frontier between homogeneous and heterogeneous catalysis have recently emerged for addressing this problem: loading the catalyst onto a dendrimer or onto a magnetic nanoparticle. In this Account, we describe representative examples of these two methods, primarily from our research group, and compare them. We then describe new chemistry that combines the benefits of these two methods of catalysis. Classic dendritic catalysis has involved either attaching the catalyst covalently at the branch termini or within the dendrimer core. We have used chelating pyridyltriazole ligands to insolubilize catalysts at the termini of dendrimers, providing an efficient, recyclable heterogeneous catalysts. With the addition of dendritic unimolecular micelles olefin metathesis reactions catalyzed by commercial Grubbs-type ruthenium-benzylidene complexes in water required unusually low amounts of catalyst. When such dendritic micelles include intradendritic ligands, both the micellar effect and ligand acceleration promote faster catalysis in water. With these types of catalysts, we could carry out azide alkyne cycloaddition ("click") chemistry with only ppm amounts of CuSO4·5H2O and sodium ascorbate under ambient conditions. Alternatively we can attach catalysts to the surface of superparamagnetic iron oxide nanoparticles (SPIONs), essentially magnetite (Fe3O4) or maghemite (γ-Fe2O3), offering the opportunity to recover the catalysts using magnets. Taking advantage of the merits of both of these strategies, we and others have developed a new generation of recyclable catalysts: dendritic magnetically recoverable catalysts. In particular, some of our catalysts with a γ-Fe2O3@SiO2 core and 1,2,3-triazole tethers and loaded with Pd nanoparticles generate strong positive dendritic effects with respect to ligand loading, catalyst loading, catalytic activity and

  4. Efficacy of intravenous zoledronic acid in the prevention and treatment of osteoporosis:A meta-analysis

    Jun Zhang; Ran Wang; Yi-Lei Zhao; Xiao-Hui Sun; Hong-Xing Zhao; Tan Lu; De-Cai Chen; Hai-Bin Xu

    2012-01-01

    Objective:To compare the effect of zoledronic acid in treatment and prevention of osteoporosis with placebo.Methods:Random control trials regarding zoledronic acid in treatment of osteoporosis were retrieved by selectingMedline,EMbase andPubmed databases tillApril2012. TheRevMan software was used for all of the statistical analysis.Results:A total of9 trials were included in this meta-analysis.The pooled effect showed that zoledronic acid could increase the bone mineral density by2.98 times compared with placebo, and reduce the rate of fracture in patients by32%.The results should the zoledronic acid intervention had significantly less serious adverse events than controls, and the odds ratio was0.81(0.76-0.87).The longer term intervention, more than12 months intervention, could gain a better prevention effect for osteoporosis(OR,95%CI forBMD was3.35,2.77-3.92; for fracture was0.67,0.54-0.82).Conclusions:This present study shows that zoledronic acid could be effective approach in the prevention of osteoporosis, and could increase the bone mineral density and reduce the risk of facture.

  5. α-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice

    α-Lipoic acid (α-LA) mimics the hypothalamic actions of leptin on food intake, energy expenditure, and activation of AMP-activated protein kinase (AMPK). To determine if, like leptin, α-LA protects against cardiac lipotoxicity, α-LA was fed to transgenic mice with cardiomyocyte-specific overexpression of the acyl CoA synthase (ACS) gene. Untreated ACS-transgenic mice died prematurely with increased triacylglycerol content and dilated cardiomyopathy, impaired systolic function and myofiber disorganization, apoptosis, and interstitial fibrosis on microscopy. In α-LA-treated ACS-transgenic mice heart size, echocardiogram and TG content were normal. Plasma TG fell 50%, hepatic-activated phospho-AMPK rose 6-fold, sterol regulatory element-binding protein-1c declined 50%, and peroxisome proliferator-activated receptor-γ cofactor-1α mRNA rose 4-fold. Since food restriction did not prevent lipotoxicity, we conclude that α-LA treatment, like hyperleptinemia, protects the heart of ACS-transgenic mice from lipotoxicity

  6. Dendritic Cells and Liver Fibrosis

    Rahman, Adeeb H.; Aloman, Costica

    2013-01-01

    Dendritic cells are a relative rare population of specialized antigen presenting cells that are distributed through most lymphoid and non-lymphoid tissues and play a critical role in linking the innate and adaptive arms of the immune system. The liver contains a heterogeneous population of dendritic cells that may contribute to liver inflammation and fibrosis through a number of mechanisms. This review summarizes current knowledge on the development and characterization of liver dendritic cel...

  7. Role and significance of polyunsaturated fatty acids in nutrition in prevention and treatment of atherosclerosis

    Ristić Vanja I.

    2003-01-01

    Full Text Available Introduction Hyperlipoproteinemia is a key factor in development of atherosclerosis, whereas regression of atherosclerosis mostly depends on decreasing the plasma level of total and LDL-cholesterol. Many studies have reported the hypocholesterolemic effect of linolenic acid. Types of polyunsaturated fatty acids (PUFA Linoleic and α-linolenic acids are essential fatty acids. The main sources of linoleic acid are vegetable seeds and of α-linolenic acid - green parts of plants. α-linolenic acid is converted to eicosapentaenoic and docosahexaenoic acid. Linoleic acid is converted into arachidonic acid competing with eicosapentaenoic acid in the starting point for synthesis of eicosanoids, which are strong regulators of cell functions and as such, very important in physiology and pathophysiology of cardiovascular system. Eicosanoids derived from eicosapentaenoic acid have different biological properties in regard to those derived from arachidonic acid, i.e. their global effects result in decreased vasoconstriction platelet aggregation and leukocyte toxicity. Role and significant of PUFA The n-6 to n-3 ratio of polyunsaturated fatty acids in the food is very important, and an optimal ratio 4 to 1 in diet is a major issue. Traditional western diets present absolute or relative deficiency of n-3 polyunsaturated fatty acids, and a ratio 15-20 to 1. In our diet fish and fish oil are sources of eicosapentaenoic and docosahexaenoic acid. Refined and processed vegetable oils change the nature of polyunsaturated fatty acids and obtained derivates have atherogenic properties.

  8. CD4+ T-cell activation is differentially modulated by bacteria-primed dendritic cells, but is generally down-regulated by n-3 polyunsaturated fatty acids

    Pedersen, Susanne Brix; Lund, Pia; Kjær, Tanja;

    2010-01-01

    Appropriate activation of CD4+ T cells is fundamental for efficient initiation and progression of acquired immune responses. Here, we showed that CD4+ T-cell activation is dependent on changes in membrane n-3 polyunsaturated fatty acids (PUFAs) and is dynamically regulated by the type of signals ...

  9. CD4+ T‐cell activation is differentially modulated by bacteria‐primed dendritic cells, but is generally down‐regulated by n‐3 polyunsaturated fatty acids

    Pedersen, Susanne Brix; Lund, Pia; Kjær, Tanja;

    2010-01-01

    Appropriate activation of CD4+ T cells is fundamental for efficient initiation and progression of acquired immune responses. Here, we showed that CD4+ T‐cell activation is dependent on changes in membrane n‐3 polyunsaturated fatty acids (PUFAs) and is dynamically regulated by the type of signals ...

  10. Dexamethasone prevents granulocyte-macrophage colony-stimulating factor-induced nuclear factor-kappaB activation, inducible nitric oxide synthase expression and nitric oxide production in a skin dendritic cell line.

    Duarte, Carlos B.; M. Celeste Lopes; Américo Figueiredo; M. Teresa Cruz; Margarida Gonçalo; Ana Luísa Vital

    2003-01-01

    AIMS: Nitric oxide (NO) has been increasingly implicated in inflammatory skin diseases, namely in allergic contact dermatitis. In this work, we investigated the effect of dexamethasone on NO production induced by the epidermal cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in a mouse fetal skin dendritic cell line. METHODS: NO production was assessed by the method of Griess. Expression of the inducible isoform of nitric oxide synthase (iNOS) protein was evaluated by wester...

  11. Conjugation of Hyaluronic Acid onto Surfaces via the Interfacial Polymerization of Dopamine to Prevent Protein Adsorption.

    Huang, Renliang; Liu, Xia; Ye, Huijun; Su, Rongxin; Qi, Wei; Wang, Libing; He, Zhimin

    2015-11-10

    A versatile, convenient, and cost-effective method that can be used for grafting antifouling materials onto different surfaces is highly desirable in many applications. Here, we report the one-step fabrication of antifouling surfaces via the polymerization of dopamine and the simultaneous deposition of anionic hyaluronic acid (HA) on Au substrates. The water contact angle of the Au surfaces decreased from 84.9° to 24.8° after the attachment of a highly uniform polydopamine (PDA)/HA hybrid film. The results of surface plasmon resonance analysis showed that the Au-PDA/HA surfaces adsorbed proteins from solutions of bovine serum albumin, lysozyme, β-lactoglobulin, fibrinogen, and soybean milk in ultralow or low amounts (4.8-31.7 ng/cm(2)). The hydrophilicity and good antifouling performance of the PDA/HA surfaces is attributable to the HA chains that probably attached onto their upper surface via hydrogen bonding between PDA and HA. At the same time, the electrostatic repulsion between PDA and HA probably prevents the aggregation of PDA, resulting in the formation of a highly uniform PDA/HA hybrid film with the HA chains (with a stretched structure) on the upper surface. We also developed a simple method for removing this PDA/HA film and recycling the Au substrates by using an aqueous solution of NaOH as the hydrolyzing agent. The Au surface remained undamaged, and a PDA/HA film could be redeposited on the surface, with the surface exhibiting good antifouling performance even after 10 such cycles. Finally, it was found that this grafting method is applicable to other substrates, including epoxy resins, polystyrene, glass, and steel, owing to the strong adhesion of PDA with these substrates. PMID:26488547

  12. Structured triacylglycerol containing behenic and oleic acids suppresses triacylglycerol absorption and prevents obesity in rats

    Takamatsu Kiyoharu

    2010-07-01

    Full Text Available Abstract Background Dietary 1(3-behenoyl-2,3(1-dioleoyl-rac-glycerol (BOO has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial hypertriacylglycerolemia in humans. In the present study, the anti-obesity activities of BOO and its inhibitory effects on lymphatic triacylglycerol (TAG absorption were investigated in rats. Methods In Experiment 1, rats were fed either BOO or soybean oil (SO diet for 6 weeks. In the BOO diet, 20% of SO was replaced with an experimental oil rich in BOO. In Experiments 2 and 3, rats cannulated in the thoracic duct were administered an emulsions containing trioleoylglycerol (OOO or an oil mixture (OOO:BOO, 9:1. Tri[1-14C]oleoylglycerol (14C-OOO was added to the emulsions administered in Experiment 3. Results No observable differences were detected in food intake or body weight gain between the BOO and SO groups in Experiment 1. Plasma and liver TAG concentrations and visceral fat weights were significantly lower in the BOO group than in the SO group. The apparent absorption rate of fat was significantly lower in the BOO group than in the SO group. In Experiment 2, the lymphatic recovery of oleic and behenic acids was significantly lower at 5 and 6 h after BOO administration than after OOO administration. In Experiment 3, the lymphatic recovery of 14C-OOO was significantly lower at 5 and 6 h after BOO administration than after OOO administration. Conclusions These results suggest that BOO prevents deposition of visceral fat and hepatic TAG by lowering and delaying intestinal absorption of TAG.

  13. Membrane Omega-3 Fatty Acid Deficiency as a Preventable Risk Factor for Comorbid Coronary Heart Disease in Major Depressive Disorder

    Robert K. McNamara

    2009-01-01

    Full Text Available Major depression disorder (MDD significantly increases the risk for coronary heart disease (CHD which is a leading cause of mortality in patients with MDD. Moreover, depression is frequently observed in a subset of patients following acute coronary syndrome (ACS and increases risk for mortality. Here evidence implicating omega-3 (n-3 fatty acid deficiency in the pathoaetiology of CHD and MDD is reviewed, and the hypothesis that n-3 fatty acid deficiency is a preventable risk factor for CHD comorbidity in MDD patients is evaluated. This hypothesis is supported by cross-national and cross-sectional epidemiological surveys finding an inverse correlation between n-3 fatty acid status and prevalence rates of both CHD and MDD, prospective studies finding that lower dietary or membrane EPA+DHA levels increase risk for both MDD and CHD, case-control studies finding that the n-3 fatty acid status of MDD patients places them at high risk for emergent CHD morbidity and mortality, meta-analyses of controlled n-3 fatty acid intervention studies finding significant advantage over placebo for reducing depression symptom severity in MDD patients, and for secondary prevention of cardiac events in CHD patients, findings that n-3 fatty acid status is inversely correlated with other documented CHD risk factors, and patients diagnosed with MDD after ACS exhibit significantly lower n-3 fatty acid status compared with nondepressed ACS patients. This body of evidence provides strong support for future studies to evaluate the effects of increasing dietary n-3 fatty acid status on CHD comorbidity and mortality in MDD patients.

  14. Asiatic Acid Prevents the Deleterious Effects of Valproic Acid on Cognition and Hippocampal Cell Proliferation and Survival

    Jariya Umka Welbat; Apiwat Sirichoat; Wunnee Chaijaroonkhanarak; Parichat Prachaney; Wanassanun Pannangrong; Poungrat Pakdeechote; Bungorn Sripanidkulchai; Peter Wigmore

    2016-01-01

    Valproic acid (VPA) is commonly prescribed as an anticonvulsant and mood stabilizer used in the treatment of epilepsy and bipolar disorder. A recent study has demonstrated that VPA reduces histone deacetylase (HDAC) activity, an action which is believed to contribute to the effects of VPA on neural stem cell proliferation and differentiation which may explain the cognitive impairments produced in rodents and patients. Asiatic acid is a triterpenoid derived from the medicinal plant Centella as...

  15. Updated estimates of neural tube defects prevented by mandatory folic Acid fortification - United States, 1995-2011.

    Williams, Jennifer; Mai, Cara T; Mulinare, Joe; Isenburg, Jennifer; Flood, Timothy J; Ethen, Mary; Frohnert, Barbara; Kirby, Russell S

    2015-01-16

    In 1992, the U.S. Public Health Service recommended that all women capable of becoming pregnant consume 400 µg of folic acid daily to prevent neural tube defects (NTDs). NTDs are major birth defects of the brain and spine that occur early in pregnancy as a result of improper closure of the embryonic neural tube, which can lead to death or varying degrees of disability. The two most common NTDs are anencephaly and spina bifida. Beginning in 1998, the United States mandated fortification of enriched cereal grain products with 140 µg of folic acid per 100 g. Immediately after mandatory fortification, the birth prevalence of NTD cases declined. Fortification was estimated to avert approximately 1,000 NTD-affected pregnancies annually. To provide updated estimates of the birth prevalence of NTDs in the period after introduction of mandatory folic acid fortification (i.e., the post-fortification period), data from 19 population-based birth defects surveillance programs in the United States, covering the years 1999-2011, were examined. After the initial decrease, NTD birth prevalence during the post-fortification period has remained relatively stable. The number of births occurring annually without NTDs that would otherwise have been affected is approximately 1,326 (95% confidence interval = 1,122-1,531). Mandatory folic acid fortification remains an effective public health intervention. There remain opportunities for prevention among women with lower folic acid intakes, especially among Hispanic women, to further reduce the prevalence of NTDs in the United States. PMID:25590678

  16. Viruses, dendritic cells and the lung

    Graham Barney S

    2001-06-01

    Full Text Available Abstract The interaction between viruses and dendritic cells (DCs is varied and complex. DCs are key elements in the development of a host response to pathogens such as viruses, but viruses have developed survival tactics to either evade or diminish the immune system that functions to kill and eliminate these micro-organisms. In the present review we summarize current concepts regarding the function of DCs in the immune system, our understanding of how viruses alter DC function to attenuate both the virus-specific and global immune response, and how we may be able to exploit DC function to prevent or treat viral infections.

  17. Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects

    Andrew E. Czeizel

    2013-11-01

    Full Text Available Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled trials indicated that periconceptional folic acid (FA-containing multivitamin supplementation prevented the major proportion (about 90% of neural-tube defects (NTD as well as a certain proportion (about 40% of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i dietary intake; (ii periconceptional supplementation; and (iii flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin’s statement: “An ounce of prevention is better than a pound of care”.

  18. Preventive maintenance basis: Volume 24 -- Battery -- flooded lead-acid (lead-calcium, lead antimony, plante). Final report

    US nuclear power plants are implementing preventive maintenance (PM) tasks with little documented basis beyond fundamental vendor information to support the tasks or their intervals. The Preventive Maintenance Basis project provides utilities with the technical basis for PM tasks and task intervals associated with 40 specific components such as valves, electric motors, pumps, and HVAC equipment. This document provides a program of preventive maintenance tasks suitable for application to flooded lead-acid batteries. The PM tasks that are recommended provide a cost-effective way to intercept the causes and mechanisms that lead to degradation and failure. They can be used in conjunction with material from other sources, to develop a complete PM program or to improve an existing program. This document provides a program of preventive maintenance (PM) tasks suitable for application to flooded lead-acid batteries. The PM tasks that are recommended provide a cost-effective way to intercept the causes and mechanisms that lead to degradation and failure. They can be used, in conjunction with material from other sources, to develop a complete PM program or to improve an existing program. Users of this information will be utility managers, supervisors, system engineers, craft technicians, and training instructors responsible for developing, optimizing, or fine-tuning PM programs

  19. Dietary Supplementation with Docosahexaenoic Acid, but Not Eicosapentanoic Acid, Dramatically Alters Cardiac Mitochondrial Phospholipid Fatty Acid Composition and Prevents Permeability Transition

    Khairallah, Ramzi J.; Sparagna, Genevieve C.; Khanna, Nishanth; O’Shea, Karen M.; Hecker, Peter A; Kristian, Tibor; Fiskum, Gary; Rosiers, Christine Des; Polster, Brian M.; Stanley, William C.

    2010-01-01

    Treatment with the ω-3 polyunsaturated fatty acids (PUFAs) docosahexanoic acid (DHA) and eicosapentanoic acid (EPA) exerts cardioprotective effects, and suppresses Ca2+-induced opening of the mitochondrial permeability transition pore (MPTP). These effects are associated with increased DHA and EPA, and lower arachidonic acid (ARA) in cardiac phospholipids. While clinical studies suggest the triglyceride lowering effects of DHA and EPA are equivalent, little is known about the independent effe...

  20. Development of dendrite polarity in Drosophila neurons

    Hill Sarah E

    2012-10-01

    Full Text Available Abstract Background Drosophila neurons have dendrites that contain minus-end-out microtubules. This microtubule arrangement is different from that of cultured mammalian neurons, which have mixed polarity microtubules in dendrites. Results To determine whether Drosophila and mammalian dendrites have a common microtubule organization during development, we analyzed microtubule polarity in Drosophila dendritic arborization neuron dendrites at different stages of outgrowth from the cell body in vivo. As dendrites initially extended, they contained mixed polarity microtubules, like mammalian neurons developing in culture. Over a period of several days this mixed microtubule array gradually matured to a minus-end-out array. To determine whether features characteristic of dendrites were localized before uniform polarity was attained, we analyzed dendritic markers as dendrites developed. In all cases the markers took on their characteristic distribution while dendrites had mixed polarity. An axonal marker was also quite well excluded from dendrites throughout development, although this was perhaps more efficient in mature neurons. To confirm that dendrite character could be acquired in Drosophila while microtubules were mixed, we genetically disrupted uniform dendritic microtubule organization. Dendritic markers also localized correctly in this case. Conclusions We conclude that developing Drosophila dendrites initially have mixed microtubule polarity. Over time they mature to uniform microtubule polarity. Dendrite identity is established before the mature microtubule arrangement is attained, during the period of mixed microtubule polarity.

  1. Do Omega-3 Polyunsaturated Fatty Acids Prevent Cardiovascular Disease? A Review of the Randomized Clinical Trials

    Kimmig, Lucas M; Karalis, Dean G.

    2013-01-01

    Fish oil is rich in the omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Numerous epidemiological studies and several large randomized clinical trials have shown that modest doses of omega-3 PUFAs significantly reduce the risk of unstable angina, myocardial infarction, and sudden cardiac death as well as death in coronary artery disease and heart failure patients. Based on the scientific evidence, the American Heart Association (AHA) has ...

  2. Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle

    Jason K Kim; Gimeno, Ruth E.; Higashimori, Takamasa; Kim, Hyo-Jeong; Choi, Hyejeong; Punreddy, Sandhya; Mozell, Robin L.; TAN, GUO; Stricker-Krongrad, Alain; Hirsch, David J.; Fillmore, Jonathan J.; Liu, Zhen-Xiang; Dong, Jianying; Cline, Gary; Stahl, Andreas

    2004-01-01

    Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid transport protein 1 (FATP1) is an acyl-CoA synthetase highly expressed in skeletal muscle and modulates fatty acid uptake and metabolism by converting fatty acids into fatty acyl-CoA. To investigate the role of FATP1 in glucose homeostasis and in the pathogenesis of insulin resistance, we examined the e...

  3. Conjugated linoleic acid as a potential protective factor in prevention of breast cancer 

    Agnieszka Białek

    2013-01-01

    Full Text Available Cancers are the second leading cause of deaths in Poland, among both women and men. Breast cancer is the malignancy most frequently diagnosed in women. In 2008 mammary cancer was diagnosed in up to 14 500 patients. It is also the second most common cause of cancer deaths among women in our country. Although the etiology of most cases of this disease is not known, risk factors include a variety of nutritional factors. The amount of fat consumed in the diet and the quantity and quality of fatty acids are especially crucial. Among fatty acids to which great importance in modification of cancer risk is attributed are conjugated linoleic acid. Conjugated linoleic acids (CLA are a group of positional and geometric isomers of linoleic acid, with a conjugated double bond system in the carbon chain. The main natural source of them is milk and dairy products and meat of different species of ruminants, in which cis-9, trans-11 octadecadienoic acid (rumenic acid occurs in the largest quantities, constituting over 90�0of the total pool of CLA. Another important isomer is trans-10, cis-12 octadecadienoic acid, which occurs with rumenic acid in dietary supplements, usually in the ratio 1:1. Surveys conducted show their possible health promoting effects in obesity, atherosclerosis, cardiovascular diseases, osteoporosis, diabetes, insulin resistance, inflammation, and various types of cancer, especially breast cancer. 

  4. Dendritic silver nanostructures obtained via one-step electrosynthesis: effect of nonanesulfonic acid and polyvinylpyrrolidone as additives on the analytical performance for hydrogen peroxide sensing

    Guadagnini, Lorella, E-mail: lorella.guadagnini2@unibo.it; Ballarin, Barbara, E-mail: barbara.ballarin@unibo.it; Tonelli, Domenica [University of Bologna, Department of Industrial Chemistry ' Toso Montanari' (Italy)

    2013-10-15

    The electrochemical deposition of silver nanodendrites (AgNDs) on pure graphite sheet (PGS) electrodes, both in the absence of surfactant/templates and in the presence of 1-nonanesulfonic acid (NS) or polyvinylpyrrolidone (PVP) additives, is reported. The synthesis carried out without additives and with NS produced a bigger amount of large size AgNDs (dimension of 1-5 {mu}m), with scarce influence played by NS, while the deposition with PVP favoured the formation of smaller spherical particles (with average diameter below 150 nm). The performances of the electrodes towards the electroreduction of H{sub 2}O{sub 2} were investigated by chronoamperometry at -0.4 V and at more cathodic applied potentials (-0.6 and -0.8 V). The electrodes fabricated without additives and in the presence of NS displayed similar performances, while those fabricated with PVP exhibited significantly lower sensitivity. This suggests that AgNDs present enhanced electrocatalytic activity in respect to the spherical aggregates, since the Ag amount deposited on PGS was practically the same. The best amperometric responses among those recorded at -0.4 V in PBS (pH 6.7) exhibited a linear range extending from 0.1 to 3.5 mM, a detection limit of about 20 {mu}M and a sensitivity close to 200 mA M{sup -1} cm{sup -2}. The proposed electrodes display sensitivities which are markedly better than those reported in the literature for similar Ag-based sensors.

  5. Dendritic silver nanostructures obtained via one-step electrosynthesis: effect of nonanesulfonic acid and polyvinylpyrrolidone as additives on the analytical performance for hydrogen peroxide sensing

    The electrochemical deposition of silver nanodendrites (AgNDs) on pure graphite sheet (PGS) electrodes, both in the absence of surfactant/templates and in the presence of 1-nonanesulfonic acid (NS) or polyvinylpyrrolidone (PVP) additives, is reported. The synthesis carried out without additives and with NS produced a bigger amount of large size AgNDs (dimension of 1–5 μm), with scarce influence played by NS, while the deposition with PVP favoured the formation of smaller spherical particles (with average diameter below 150 nm). The performances of the electrodes towards the electroreduction of H2O2 were investigated by chronoamperometry at −0.4 V and at more cathodic applied potentials (−0.6 and −0.8 V). The electrodes fabricated without additives and in the presence of NS displayed similar performances, while those fabricated with PVP exhibited significantly lower sensitivity. This suggests that AgNDs present enhanced electrocatalytic activity in respect to the spherical aggregates, since the Ag amount deposited on PGS was practically the same. The best amperometric responses among those recorded at −0.4 V in PBS (pH 6.7) exhibited a linear range extending from 0.1 to 3.5 mM, a detection limit of about 20 μM and a sensitivity close to 200 mA M−1 cm−2. The proposed electrodes display sensitivities which are markedly better than those reported in the literature for similar Ag-based sensors

  6. Dendrite Injury Triggers DLK-Independent Regeneration

    Michelle C. Stone

    2014-01-01

    Full Text Available Axon injury triggers regeneration through activation of a conserved kinase cascade, which includes the dual leucine zipper kinase (DLK. Although dendrites are damaged during stroke, traumatic brain injury, and seizure, it is not known whether mature neurons monitor dendrite injury and initiate regeneration. We probed the response to dendrite damage using model Drosophila neurons. Two larval neuron types regrew dendrites in distinct ways after all dendrites were removed. Dendrite regeneration was also triggered by injury in adults. Next, we tested whether dendrite injury was initiated with the same machinery as axon injury. Surprisingly, DLK, JNK, and fos were dispensable for dendrite regeneration. Moreover, this MAP kinase pathway was not activated by injury to dendrites. Thus, neurons respond to dendrite damage and initiate regeneration without using the conserved DLK cascade that triggers axon regeneration.

  7. Dendritic cells in asthma.

    van Helden, Mary J; Lambrecht, Bart N

    2013-12-01

    The lungs are constantly exposed to antigens, most of which are non-pathogenic and do not require the induction of an immune response. Dendritic cells (DCs) are situated at the basolateral site of the lungs and continuously scan the environment to detect the presence of pathogens and subsequently initiate an immune response. They are a heterogeneous population of antigen-presenting cells that exert specific functions. Compelling evidence is now provided that DCs are both sufficient and necessary to induce allergic responses against several inhaled harmless allergens. How various DC subsets exactly contribute to the induction of allergic asthma is currently a subject of intense investigation. We here review the current progress in this field. PMID:24455765

  8. Treatment and prevention systems for acid mine drainage and halogenated contaminants

    Jin, Song; Fallgren, Paul H.; Morris, Jeffrey M.

    2012-01-31

    Embodiments include treatments for acid mine drainage generation sources (10 perhaps by injection of at least one substrate (11) and biologically constructing a protective biofilm (13) on acid mine drainage generation source materials (14). Further embodiments include treatments for degradation of contaminated water environments (17) with substrates such as returned milk and the like.

  9. Nutraceuticals and prevention of atherosclerosis: focus on omega-3 polyunsaturated fatty acids and Mediterranean diet polyphenols

    Massaro, Marika; Scoditti, Egeria; Carluccio, Maria Annunziata; De Caterina, Raffaele

    2010-01-01

    Nutraceuticals are potentially healthful foods that play a role in maintaining human well being, enhancing health and preventing, or even treating, specific diseases. More than for any other diseases, cardiovascular diseases occur in association with risk factors that are amenable to prevention or treatment by nutraceutical interventions. Several ingredients marketed for use in dietary supplements address such risk factors. The ability of nutraceuticals to favorably influence cardiovascular r...

  10. Mechanisms of mouse spleen dendritic cell function in the generation of influenza-specific, cytolytic T lymphocytes

    1992-01-01

    We have evaluated the capacity of dendritic cells to function as antigen-presenting cells (APCs) for influenza and have examined their mechanism of action. Virus-pulsed dendritic cells were 100 times more efficient than bulk spleen cells in stimulating cytotoxic T lymphocyte (CTL) formation. The induction of CTLs required neither exogenous lymphokines nor APCs in the responding T cell population. Infectious virus entered dendritic cells through intracellular acidic vacuoles and directed the s...

  11. Can dendritic cells see light?

    Chen, Aaron C.-H.; Huang, Ying-Ying; Sharma, Sulbha K.; Hamblin, Michael R.

    2010-02-01

    There are many reports showing that low-level light/laser therapy (LLLT) can enhance wound healing, upregulate cell proliferation and has anti-apoptotic effects by activating intracellular protective genes. In the field of immune response study, it is not known with any certainty whether light/laser is proinflammatory or anti-inflammatory. Increasingly in recent times dendritic cells have been found to play an important role in inflammation and the immunological response. In this study, we try to look at the impact of low level near infrared light (810-nm) on murine bone-marrow derived dendritic cells. Changes in surface markers, including MHC II, CD80 and CD11c and the secretion of interleukins induced by light may provide additional evidence to reveal the mystery of how light affects the maturation of dendritic cells as well how these light-induced mature dendritic cells would affect the activation of adaptive immune response.

  12. Luteolin prevents uric acid-induced pancreatic β-cell dysfunction

    Ding, Ying; Shi, Xuhui; Shuai, Xuanyu; Xu, Yuemei; Liu, Yun; Liang, Xiubin; Wei, Dong; Su, Dongming

    2014-01-01

    Abstract Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to a...

  13. Oral Ascorbic Acid in Combination with Beta-Blockers Is More Effective than Beta-Blockers Alone in the Prevention of Atrial Fibrillation after Coronary Artery Bypass Grafting

    Eslami, Masoud; Badkoubeh, Roya Sattarzadeh; Mousavi, Mehdi; Radmehr, Hassan; Salehi, Mehrdad; Tavakoli, Nafiseh; Avadi, Mohamad Reza

    2007-01-01

    Because adrenergic beta antagonists are not sufficient to prevent atrial fibrillation after coronary artery bypass grafting, this prospective, randomized trial was designed to evaluate the effects of ascorbic acid as an adjunct to β-blockers.

  14. N-3 (Omega-3) Fatty Acids in Postpartum Depression: Implications for Prevention and Treatment

    Beth Levant

    2011-01-01

    A growing body of clinical and epidemiological evidence suggests that low dietary intake and/or tissue levels of n-3 (omega-3) polyunsaturated fatty acids (PUFAs) are associated with postpartum depression. Low tissue levels of n-3 PUFAs, particularly docosahexaenoic acid (DHA), are reported in patients with either postpartum or nonpuerperal depression. Moreover, the physiological demands of pregnancy and lactation put childbearing women at particular risk of experiencing a loss of DHA from ti...

  15. [Prevention and therapeutic effects of sika deer velvet collagen hydrolysate on osteoporosis in rats by retinoic acid].

    Li, Yinqing; Zhao, Yu; Sun, Xiaodi; Qu, Xiaobo

    2010-03-01

    The objective was to evaluate the preventive and therapeutic effects of the collagen hydrolysate extracted from Sika deer velvet (CSDV) on osteoporosis rats induced by retinoicacid. Histomorphometric indices and serum biochemical parameters were measured in osteoporosis rats treated with/without antler collagen and in sham-operated rats. Our results were as follows: compared with the osteoporosis group, significant elevation in the levels of bone mineral density (BMD), Ca, P and static histomorphometric indexes and biomechanical properties, but reduction in the level of serum alkaline phosphatase (ALP) were observed in antler collagen-treated groups. However, the above function with the collagenase solution velvet material varied with the different doses. In conclusion, the extracted collagen is found to play a role in the prevention and treatment of osteoporosis rats by retinoic acid. PMID:20545204

  16. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Jeong, Soyeon; Shin, Soyeon; Lim, Kyu [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Infection Signaling Network Research Center, Chungnam National University, Daejeon (Korea, Republic of); Heo, Jun Young, E-mail: junyoung3@gmail.com [Brainscience Institute, Chungnam National University, Daejeon (Korea, Republic of); Kweon, Gi Ryang, E-mail: mitochondria@cnu.ac.kr [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Infection Signaling Network Research Center, Chungnam National University, Daejeon (Korea, Republic of)

    2015-01-30

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

  17. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis

  18. Periconceptional use of folic acid and risk of miscarriage – Findings of Oral Cleft Prevention Program in Brazil

    Vila-Nova, C; Wehby, GL; Queirós, F; Chakraborty, H; Félix, TM; Goco, N; J. Moore; Gewehr, EV; Lins, L.; Affonso, CMC; Murray, JC

    2013-01-01

    We report on the risk of miscarriage due to high dosage periconceptional folic acid (FA) supplementation from a double blind randomized clinical trial for prevention of orofacial clefts in Brazil. The miscarriage rate was 14.2% in the low dose FA group (0.4 mg per day) and 11.3% for the high dose (4 mg per day) group (p=0.4877); the population miscarriage rate is 14%. These results indicate that high dose FA does not increase miscarriage risk in this population and add further information to ...

  19. NSAID-associated adverse effects and acid control aids to prevent them: a review of current treatment options.

    Naesdal, Jørgen; Brown, Kurt

    2006-01-01

    NSAIDs are central to the clinical management of a wide range of conditions. However, NSAIDs in combination with gastric acid, which has been shown to play a central role in upper gastrointestinal (GI) events, can damage the gastroduodenal mucosa and result in dyspeptic symptoms and peptic lesions such as ulceration.NSAID-associated GI mucosal injury is an important clinical problem. Gastroduodenal ulcers or ulcer complications occur in up to 25% of patients receiving NSAIDs. However, these toxicities are often not preceded by indicative symptoms. Data obtained from the Arthritis, Rheumatism, and Aging Medical Information System have shown that 50-60% of NSAID-associated peptic ulcer cases can remain clinically silent and do not present until complications occur. Therefore, prophylactic treatment to prevent GI complications may be necessary in a substantial proportion of NSAID users, especially those in groups associated with a high risk of developing these complications. Use of cyclo-oxygenase (COX)-2 selective NSAIDs, also known as 'coxibs', substantially reduces the incidence of upper GI toxicities seen with non-selective NSAIDs. However, there are concerns regarding the cardiovascular safety of coxibs. For this reason, the US FDA recommends minimal use of coxibs and only when strictly necessary. Additionally, rofecoxib has been removed from the US market and sales of valdecoxib have been suspended. Furthermore, upper GI toxicities still occur in patients receiving coxibs. Therefore, cotherapies are required to prevent and/or heal upper GI effects associated with NSAID use. Effective prophylactic and treatment strategies include misoprostol, histamine H(2) receptor antagonists and proton pump inhibitors (PPIs). The key role that gastric acid plays in upper GI adverse events among NSAID users suggests that it is important to choose the most effective agent for acid control to alleviate symptoms, heal mucosal erosions and improve the reduced quality of life in

  20. Antimicrobial activity of transition metal acid MoO{sub 3} prevents microbial growth on material surfaces

    Zollfrank, Cordt, E-mail: cordt.zollfrank@ww.uni-erlangen.de [University of Erlangen-Nuremberg, Department of Materials Science and Engineering 3-Glass and Ceramics, Martensstr. 5, D-91058 Erlangen (Germany); Gutbrod, Kai [University of Erlangen-Nuremberg, Department of Materials Science and Engineering 3-Glass and Ceramics, Martensstr. 5, D-91058 Erlangen (Germany); Wechsler, Peter [LEONI Kabel GmbH, Stieberstrasse 5, D-91154 Roth (Germany); Guggenbichler, Josef Peter [Laboratory for the Development of Healthcare Products, Leitweg 23, A-6345 Koessen (Austria)

    2012-01-01

    Serious infectious complications of patients in healthcare settings are often transmitted by materials and devices colonised by microorganisms (nosocomial infections). Current strategies to generate material surfaces with an antimicrobial activity suffer from the consumption of the antimicrobial agent and emerging multidrug-resistant pathogens amongst others. Consequently, materials surfaces exhibiting a permanent antimicrobial activity without the risk of generating resistant microorganisms are desirable. This publication reports on the extraordinary efficient antimicrobial properties of transition metal acids such as molybdic acid (H{sub 2}MoO{sub 4}), which is based on molybdenum trioxide (MoO{sub 3}). The modification of various materials (e.g. polymers, metals) with MoO{sub 3} particles or sol-gel derived coatings showed that the modified materials surfaces were practically free of microorganisms six hours after contamination with infectious agents. The antimicrobial activity is based on the formation of an acidic surface deteriorating cell growth and proliferation. The application of transition metal acids as antimicrobial surface agents is an innovative approach to prevent the dissemination of microorganisms in healthcare units and public environments. Highlights: Black-Right-Pointing-Pointer The presented modifications of materials surfaces with MoO{sub 3} are non-cytotoxic and decrease biofilm growth and bacteria transmission. Black-Right-Pointing-Pointer The material is insensitive towards emerging resistances of bacteria. Black-Right-Pointing-Pointer Strong potential to reduce spreading of infectious agents on inanimate surfaces.

  1. Vitamin E supplementation does not prevent ethanol-reduced hepatic retinoic acid levels in rats

    Chronic, excessive ethanol intake can increase retinoic acid (RA) catabolism by inducing cytochrome P450 2E1 (CYP2E1). Vitamin E (VE) is an antioxidant implicated in CYP2E1 inhibition. In the current study, we hypothesized that VE supplementation inhibits CYP2E1 and decreases RA catabolism, thereby ...

  2. Kynurenic acid prevented social recognition deficits induced by MK-801 in rats

    Hliňák, Zdeněk; Krejčí, I.

    2003-01-01

    Roč. 52, č. 6 (2003), s. 805-808. ISSN 0862-8408 R&D Projects: GA ČR GA309/00/1644 Institutional research plan: CEZ:AV0Z5011922 Keywords : amnesia * kynurenic acid * MK-801 Subject RIV: FH - Neurology Impact factor: 0.939, year: 2003

  3. Electron beam treatment technology for exhaust gas for preventing acid rain

    Recently, accompanying the increase of the use of fossil fuel, the damage due to acid rain such as withering of trees and extinction of fishes and shells has occurred worldwide, and it has become a serious problem. The sulfur oxides and nitrogen oxides contained in exhaust gas are oxidized by the action of sunbeam to become sulfuric acid and nitric acid mists, which fall in the form of rain. Acid rain is closely related to the use of the coal containing high sulfur, and it hinders the use of coal which is rich energy source. In order to simplify the processing system for boiler exhaust gas and to reduce waste water and wastes, Ebara Corp. developed the dry simultaneous desulfurizing and denitrating technology utilizing electron beam in cooperation with Japan Atomic Energy Research Institute. The flow chart of the system applied to the exhaust gas treatment in a coal-fired thermal power station is shown. The mechanism of desulfurization and denitration, and the features of this system are described. The demonstration plant was constructed in a coal-fired thermal power station in Indianapolis, Indiana, USA, and the trial operation was completed in July, 1987. The test results are reported. (K.I.)

  4. Corrosion Prevention of Cold Rolled Steel Using Water Dispersible Lignosulfonic Acid Doped Polyaniline

    Viswanathan, Tito (Inventor)

    2007-01-01

    The invention provides coatings useful for preventing corrosion of metals. The coatings comprise a film-forming resin and conductive polymers comprising linearly conjugated x-systems and residues of sulfonated lignin or a sulfonated polyflavonoid or derivatives of solfonated lignin or a sulfonated polyflavonoid. The invention also provides a latex formulation of the coatings, and articles of manufacture comprising a metal substrate and a coating in contact with the metal substrate.

  5. Prediction of the long-term performance of green liquor dregs as a sealing layer to prevent the formation of acid mine drainage

    Mäkitalo, Maria; Lu, Jinmei; Maurice, Christian; Öhlander, Björn

    2015-01-01

    One of the mining industry's main concerns is the management of waste rock and tailings generated by sulfide ore extraction. Upon exposure of atmospheric oxygen, iron sulfides oxidize generating acidity. Infiltrating water form a metal-rich acidic leachate called acid mine drainage (AMD), that can cause serious environmental problems. Green liquor dregs (GLD) is a material that resists the passage of oxygen and water and could thus be used to seal mine wastes, preventing their oxidation and A...

  6. Nitro-Arachidonic Acid Prevents Angiotensin II-Induced Mitochondrial Dysfunction in a Cell Line of Kidney Proximal Tubular Cells.

    Beatriz Sánchez-Calvo

    Full Text Available Nitro-arachidonic acid (NO2-AA is a cell signaling nitroalkene that exerts anti-inflammatory activities during macrophage activation. While angiotensin II (ANG II produces an increase in reactive oxygen species (ROS production and mitochondrial dysfunction in renal tubular cells, little is known regarding the potential protective effects of NO2-AA in ANG II-mediated kidney injury. As such, this study examines the impact of NO2-AA on ANG II-induced mitochondrial dysfunction in an immortalized renal proximal tubule cell line (HK-2 cells. Treatment of HK-2 cells with ANG II increases the production of superoxide (O2●-, nitric oxide (●NO, inducible nitric oxide synthase (NOS2 expression, peroxynitrite (ONOO- and mitochondrial dysfunction. Using high-resolution respirometry, it was observed that the presence of NO2-AA prevented ANG II-mediated mitochondrial dysfunction. Attempting to address mechanism, we treated isolated rat kidney mitochondria with ONOO-, a key mediator of ANG II-induced mitochondrial damage, in the presence or absence of NO2-AA. Whereas the activity of succinate dehydrogenase (SDH and ATP synthase (ATPase were diminished upon exposure to ONOO-, they were restored by pre-incubating the mitochondria with NO2-AA. Moreover, NO2-AA prevents oxidation and nitration of mitochondrial proteins. Combined, these data demonstrate that ANG II-mediated oxidative damage and mitochondrial dysfunction is abrogated by NO2-AA, identifying this compound as a promising pharmacological tool to prevent ANG II-induced renal disease.

  7. Omega-3 polyunsaturated fatty acids: Their potential role in blood pressure prevention and management

    2010-01-01

    Omega-3 polyunsaturated fatty acids (PUFAs) from fish and fish oils appear to protect against coronary heart disease: their dietary intake is in fact inversely associated to cardiovascular disease morbidity/mortality in population studies. Recent evidence suggests that at least part of their heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. In fact, omega-3 PUFAs exhibit wide-ranging biological actions that include regulating both vaso...

  8. Preventive effect of ursodeoxycholic acid on parenteral nutrition-associated liver disease in infants

    Simić Dušica; Milojević Irina; Bogićević Dragana; Milenović Miodrag; Radlović Vladimir; Drašković Biljana; Uram-Benka Anna; Sinđić Sanja; Maksimović Ružica

    2014-01-01

    Introduction. Parenteral nutrition-associated cholestasis is well recognized phenomenon in the term and preterm infant receiving long-term parenteral nutrition. Objectives. The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) use on cholestasis in newborns on prolonged TPN. Methods. A total of 56 infants were enrolled in this retrospective study: control group consisted of lower (1500 g) birth weight infants (n=30), as well as the...

  9. Fusarium Head Blight Control and Prevention of Mycotoxin Contamination in Wheat with Botanicals and Tannic Acid

    Hans-Rudolf Forrer; Tomke Musa; Fabienne Schwab; Eveline Jenny; Bucheli, Thomas D.; Felix E. Wettstein; Susanne Vogelgsang

    2014-01-01

    Suspensions or solutions with 1% of Chinese galls (Galla chinensis, GC) or 1% of tannic acid (TA), inhibited germination of conidia or mycelium growth of Fusarium graminearum (FG) by 98%–100% or by 75%–80%, respectively, whereas dried bark from buckthorn (Frangula alnus, FA) showed no effect at this concentration. In climate chamber experiments where the wheat variety “Apogee” was artificially inoculated with FG and F. crookwellense (FCr) and treated with 5% suspensions of TA, GC and FA, the ...

  10. A full-scale porous reactive wall for prevention of acid mine drainage

    The generation and release of acidic drainage containing high concentrations of dissolved metals from decommissioned mine wastes is an environmental problem of international scale. A potential solution to many acid drainage problems is the installation of permeable reactive walls into aquifers affected by drainage water derived from mine waste materials. A permeable reactive wall installed into an aquifer impacted by low-quality mine drainage waters was installed in August 1995 at the Nickel Rim mine site near Sudbury, Ontario. The reactive mixture, containing organic matter, was designed to promote bacterially mediated sulfate reduction and subsequent metal sulfide precipitation. The reactive wall is installed to an average depth of 12 feet (3.6 m) and is 49 feet (15 m) long perpendicular to ground water flow. The wall thickness (flow path length) is 13 feet (4 m). Initial results, collected nine months after installation, indicate that sulfate reduction and metal sulfide precipitation is occurring. The reactive wall has effectively removed the capacity of the ground water to generate acidity on discharge to the surface. Calculations based on comparison to previously run laboratory column experiments indicate that the reactive wall has potential to remain effective for at least 15 years

  11. The Deterministic Dendritic Cell Algorithm

    Greensmith, Julie

    2010-01-01

    The Dendritic Cell Algorithm is an immune-inspired algorithm orig- inally based on the function of natural dendritic cells. The original instantiation of the algorithm is a highly stochastic algorithm. While the performance of the algorithm is good when applied to large real-time datasets, it is difficult to anal- yse due to the number of random-based elements. In this paper a deterministic version of the algorithm is proposed, implemented and tested using a port scan dataset to provide a controllable system. This version consists of a controllable amount of parameters, which are experimented with in this paper. In addition the effects are examined of the use of time windows and variation on the number of cells, both which are shown to influence the algorithm. Finally a novel metric for the assessment of the algorithms output is introduced and proves to be a more sensitive metric than the metric used with the original Dendritic Cell Algorithm.

  12. The influence of infectious factors on dendritic cell apoptosis

    Kubicka-Sierszen, Agata; Grzegorczyk, Janina Ł.

    2015-01-01

    Pathogens can have a negative influence on dendritic cells (DCs), causing their apoptosis, which prevents active presentation of foreign antigens. It results in a state of immunosuppression which makes the body susceptible to secondary infections. Infected immature DCs have lower expression of co-stimulatory and adhesion molecules, reduced ability to secrete cytokines and an inhibited maturation process and are incapable of effective antigen presentation and activation of T-lymphocytes. In so...

  13. Bioactive 1,4-dihydroisonicotinic acid derivatives prevent oxidative damage of liver cells.

    Borovic, Suzana; Tirzitis, Gunars; Tirzite, Dace; Cipak, Ana; Khoschsorur, Gholam A; Waeg, Georg; Tatzber, Franz; Scukanec-Spoljar, Mira; Zarkovic, Neven

    2006-05-10

    1,4-Dihydroisonicotinic acid derivatives (1,4-DHINA) are compounds closely related to derivatives of 1,4-dihydropyridine, a well-known calcium channel antagonists. 1,4-DHINA we used were derived from a well-known antioxidant Diludin. Although some compounds have neuromodulatory or antimutagenic properties, their activity mechanisms are not well known. This study was performed to obtain data on antioxidant and bioprotective activities of: 2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydroisonicotinic acid (Ia); sodium 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)glutamate (Ib) and sodium 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)ethane-sulphate (Ic). 1,4-DHINA's activities were studied in comparison to Trolox by: N,N-Diphenyl-N'-picrylhydrazyl (DPPH*), deoxyribose degradation, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical scavenging and antioxidative capacity assays; copper-induced lipid peroxidation of cultured rat liver cells (malondialdehyde determination by high performance liquid chromatography and 4-hydroxynonenal-protein conjugates by dot-blot); (3)H-thymidine incorporation and trypan blue assay for liver cells growth and viability. In all assays used Ia was the most potent antioxidant. Ia was also a potent antioxidant at non-toxic concentrations for liver cell cultures. It completely abolished, while Ic only slightly decreased copper-induced lipid peroxidation of liver cells. Thus, antioxidant capacities are important activity principle of Ia, which was even superior to Trolox in the cell cultures used, while activity principles of Ic and Ib remain yet to be determined. PMID:16600211

  14. An inverse approach for elucidating dendritic function

    Benjamin Torben-Nielsen

    2010-09-01

    Full Text Available We outline an inverse approach for investigating dendritic function-structure relationships by optimizing dendritic trees for a-priori chosen computational functions. The inverse approach can be applied in two different ways. First, we can use it as a `hypothesis generator' in which we optimize dendrites for a function of general interest. The optimization yields an artificial dendrite that is subsequently compared to real neurons. This comparison potentially allows us to propose hypotheses about the function of real neurons. In this way, we investigated dendrites that optimally perform input-order detection. Second, we can use it as a `function confirmation' by optimizing dendrites for functions hypothesized to be performed by classes of neurons. If the optimized, artificial, dendrites resemble the dendrites of real neurons the artificial dendrites corroborate the hypothesized function of the real neuron. Moreover, properties of the artificial dendrites can lead to predictions about yet unmeasured properties. In this way, we investigated wide-field motion integration performed by the VS cells of the fly visual system. In outlining the inverse approach and two applications, we also elaborate on the nature of dendritic function. We furthermore discuss the role of optimality in assigning functions to dendrites and point out interesting future directions.

  15. Exploiting the Physicochemical Properties of Dendritic Polymers for Environmental and Biological Applications

    Bhattacharya, Priyanka; Geitner, Nicholas K.; Sarupria, Sapna; Ke, Pu Chun

    2013-04-07

    In this Perspective we first examine the rich physicochemical properties of dendritic polymers for hosting cations, anions, and polyaromatic hydrocarbons. We then extrapolate these conceptual discussions to the use of dendritic polymers for humic acid antifouling, oil dispersion, copper sensing, and fullerenol remediation. In addition, we review the state-of-the-art of dendrimer research and elaborate on their 10 implications for water purification, environmental remediation, nanomedicine, and energy harvesting.

  16. The omega-3 fatty acid, eicosapentaenoic acid (EPA, prevents the damaging effects of tumour necrosis factor (TNF-alpha during murine skeletal muscle cell differentiation

    Pearson Stephen

    2008-07-01

    Full Text Available Abstract Background Eicosapentaenoic acid (EPA is a ώ-3 polyunsaturated fatty acid with anti-inflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present. It is also reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF-α are associated with muscle wasting, exerted through inhibition of myogenic differentiation and enhanced apoptosis. These findings led us to hypothesize that EPA may have a protective effect against skeletal muscle damage induced by the actions of TNF-α. Results The deleterious effects of TNF-α on C2C12 myogenesis were completely inhibited by co-treatment with EPA. Thus, EPA prevented the TNF-mediated loss of MyHC expression and significantly increased myogenic fusion (p p p p p p Conclusion In conclusion, EPA has a protective action against the damaging effects of TNF-α on C2C12 myogenesis. These findings support further investigations of EPA as a potential therapeutic agent during skeletal muscle regeneration following injury.

  17. Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy.

    Kurahashi, Toshihiro; Lee, Jaeyong; Nabeshima, Atsunori; Homma, Takujiro; Kang, Eun Sil; Saito, Yuka; Yamada, Sohsuke; Nakayama, Toshiyuki; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi

    2016-08-15

    Aldehyde reductase (AKR1A) plays a role in the biosynthesis of ascorbic acid (AsA), and AKR1A-deficient mice produce about 10-15% of the AsA that is produced by wild-type mice. We found that acetaminophen (AAP) hepatotoxicity was aggravated in AKR1A-deficient mice. The pre-administration of AsA in the drinking water markedly ameliorated the AAP hepatotoxicity in the AKR1A-deficient mice. Treatment of the mice with AAP decreased both glutathione and AsA levels in the liver in the early phase after AAP administration, and an AsA deficiency delayed the recovery of the glutathione content in the healing phase. While in cysteine supply systems; a neutral amino acid transporter ASCT1, a cystine transporter xCT, enzymes for the transsulfuration pathway, and autophagy markers, were all elevated in the liver as the result of the AAP treatment, the AsA deficiency suppressed their induction. Thus, AsA appeared to exert a protective effect against AAP hepatotoxicity by ameliorating the supply of cysteine that is available for glutathione synthesis as a whole. Because some drugs produce reactive oxygen species, resulting in the consumption of glutathione during the metabolic process, the intake of sufficient amounts of AsA would be beneficial for protecting against the hepatic damage caused by such drugs. PMID:27288086

  18. role of conjugated linoleic acid in the prevention of radiation hazard in male rats

    the objective of the present study was to examine the effect of conjugated linoleic acid (CLA) as a natural product in minimizing the radiation hazards. male rats were assigned to six groups each of 7 animals throughout six weeks, fed 1% CLA (wt/wt)added to commercial diet in the form of milk powder 182 g/kg diet. rats exposed to 6 Gy whole body gamma irradiation showed significant increase in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C).triglycerides (TG), atherosclerosis index, total lipid (TL), phospholipids (ph-lipids), malondialdehyde (MDA), urea,creatinine, uric acid, calcium (Ca) and phosphorous levels associated with decrease in high density lipoprotein-cholesterol (HDL-C), activity of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status, body weight, testes weight and testosterone both irradiated and non-irradiated milk powder administrated to irradiated rat groups minimized the radiation damage in the assayed parameters indicating its beneficial role as a promising antioxidant in scavenging free radicals and reactive oxygen species

  19. Docosahexaenoic Acid Supplementation during Pregnancy: A Potential Tool to Prevent Membrane Rupture and Preterm Labor

    Emanuela Pietrantoni

    2014-05-01

    Full Text Available Polyunsaturated fatty acids (PUFAs are required to maintain the fluidity, permeability and integrity of cell membranes. Maternal dietary supplementation with ω-3 PUFAs during pregnancy has beneficial effects, including increased gestational length and reduced risk of pregnancy complications. Significant amounts of ω-3 docosahexaenoic acid (DHA are transferred from maternal to fetal blood, hence ensuring high levels of DHA in the placenta and fetal bloodstream and tissues. Fetal DHA demand increases exponentially with gestational age, especially in the third trimester, due to fetal development. According to the World Health Organization (WHO and the Food and Agriculture Organization of the United Nations (FAO, a daily intake of DHA is recommended during pregnancy. Omega-3 PUFAs are involved in several anti-inflammatory, pro-resolving and anti-oxidative pathways. Several placental disorders, such as intrauterine growth restriction, premature rupture of membranes (PROM and preterm-PROM (pPROM, are associated with placental inflammation and oxidative stress. This pilot study reports on a preliminary evaluation of the significance of the daily DHA administration on PROM and pPROM events in healthy pregnant women. Further extensive clinical trials will be necessary to fully elucidate the correlation between DHA administration during pregnancy and PROM/pPROM occurrence, which is related in turn to gestational duration and overall fetal health.

  20. Postischemic fish oil treatment restores long-term retrograde memory and dendritic density: An analysis of the time window of efficacy.

    Bacarin, Cristiano Correia; Godinho, Jaqueline; de Oliveira, Rúbia Maria Weffort; Matsushita, Makoto; Gohara, Aline Kirie; Cardozo-Filho, Lúcio; Lima, Jéssica de Carvalho; Previdelli, Isolde Santos; Melo, Silvana Regina; Ribeiro, Matheus Henrique Dal Molin; Milani, Humberto

    2016-09-15

    We reported that fish oil (FO) prevented the loss of spatial memory caused by transient, global cerebral ischemia (TGCI), provided the treatment covered the first days prior to and after ischemia. Continuing these studies, trained rats were subjected to TGCI, and FO was administered for 10days, with a time window of efficacy (TWE) of 4, 8 or 12h post-ischemia. Retrograde memory was assessed up to 43days after TGCI. In another experiment, ischemic rats received FO with a 4- or 12-h TWE, and dendritic density was assessed in the hippocampus and cerebral cortex. The brain lipid profile was evaluated in sham-operated and ischemic rats that were treated with FO or vehicle with a 4-h TWE. Ischemia-induced retrograde amnesia was prevented by FO administration that was initiated with either a 4- or 8-h TWE. Fish oil was ineffective after a 12-h TWE. Independent of the TWE, FO did not prevent ischemic neuronal death. In the hippocampus, but not cerebral cortex, TGCI-induced dendritic loss was prevented by FO with a 4-h TWE but not 12-h TWE. The level of docosahexaenoic acid almost doubled in the hippocampus in ischemic, FO-treated rats (4-h TWE). The data indicate that (i) the anti-amnesic effect of FO can be observed with a TWE of up to 8h, (ii) the stimulation of dendritic neuroplasticity may have contributed to this effect, and (iii) DHA in FO may be the main active constituent in FO that mediates the cognitive and neuroplasticity effects on TGCI. PMID:27235715

  1. Acidity-induced watercourse defects and their prevention on the River Sanginjoki; Happamuuden aiheuttamat vesistoehaitat ja niiden torjuntakeinot Sanginjoella

    Tertsunen, J.; Martinmaeki, K.; Heikkinen, K. [and others

    2012-11-15

    As the first tributary of the River Oulujoki, the River Sanginjoki is one of the most important recreational areas in the Oulu region. It is also the closest potential reproduction area for salmon and trout using the Merikoski fishway. During flood peaks, occasional low pH values reduce the recreational and ecological value of the River Sanginjoki. The origin of low pH values was located as part of the 'City and Water - Improving the recreational value and ecological restoration of River Sanginjoki -project', during the years 2008-2011. This project involved largescale monitoring of the River Sanginjoki area for pH changes, while methods for preventing and reducing low pH values were tested. Based on the project's results, guidelines were drawn up for controlling problems associated with low pH values. The report also contains general information on the River Sanginjoki and its watershed, the river's ecological state and the development of its water quality. The results demonstrated a connection between low pH values and high discharges, but the lowest pH values were measured during summer and autumn rain floods in particular. A water sample analysis with other information showed that low pH values mainly originate in soil, land use and vegetation. The origin of acid runoff mainly lies in organic acids from peatlands and moss, but local factors such as acid sulphate soils and black shales may also contribute. Due to acidic peatlands, the water of the River Sanginjoki has naturally been slightly acidic, but ditch drainage of peat- and forestland has probably increased this effect. The effect of the restoration and water protection methods used in the project varied. Some methods proved effective and can be suggested for practical use at the Sanginjoki watershed, as well as other watersheds suffering from the same problems. Development of these methods should be continued, to improve their effectiveness and durability. Although defects due to

  2. Implementing preventive iron-folic acid supplementation among women of reproductive age in some Western Pacific countries: possibilities and challenges.

    Smitasiri, Suttilak; Solon, Florentino S

    2005-12-01

    Lack of effective implementation mechanisms is identified as a major obstacle in the prevention and control of iron-deficiency anemia. This paper discusses experiences gained from implementing iron-folic acid supplementation in the Philippines, Vietnam, and Cambodia. The understanding of contextual elements is proposed as a foundation for planning interventions. Moreover, it is suggested that a social marketing framework should provide a way of thinking about how to influence related behaviors. The application of a social marketing framework applied using a "5 P's" approach: public relations and collaboration, product, price, place, and promotion, is described, as well as enabling factors (possibilities) and inhibiting factors (challenges) of this approach. Although a program to improve iron nutrition among women of reproductive age may not be simple to implement, it is essential to enhancing health, human development, and economic advancement in developing countries. PMID:16466083

  3. Three-Step Model for Polarized Sorting of KIF17 into Dendrites.

    Franker, Mariella A; Esteves da Silva, Marta; Tas, Roderick P; Tortosa, Elena; Cao, Yujie; Frias, Cátia P; Janssen, Anne F J; Wulf, Phebe S; Kapitein, Lukas C; Hoogenraad, Casper C

    2016-07-11

    Kinesin and dynein motors drive bidirectional cargo transport along microtubules and have a critical role in polarized cargo trafficking in neurons [1, 2]. The kinesin-2 family protein KIF17 is a dendrite-specific motor protein and has been shown to interact with several dendritic cargoes [3-7]. However, the mechanism underlying the dendritic targeting of KIF17 remains poorly understood [8-11]. Using live-cell imaging combined with inducible trafficking assays to directly probe KIF17 motor activity in living neurons, we found that the polarized sorting of KIF17 to dendrites is regulated in multiple steps. First, cargo binding of KIF17 relieves autoinhibition and initiates microtubule-based cargo transport. Second, KIF17 does not autonomously target dendrites, but enters the axon where the actin cytoskeleton at the axon initial segment (AIS) prevents KIF17 vesicles from moving further into the axon. Third, dynein-based motor activity is able to redirect KIF17-coupled cargoes into dendrites. We propose a three-step model for polarized targeting of KIF17, in which the collective function of multiple motor teams is required for proper dendritic sorting. PMID:27265394

  4. Intrinsic and extrinsic mechanisms of dendritic morphogenesis.

    Dong, Xintong; Shen, Kang; Bülow, Hannes E

    2015-01-01

    The complex, branched morphology of dendrites is a cardinal feature of neurons and has been used as a criterion for cell type identification since the beginning of neurobiology. Regulated dendritic outgrowth and branching during development form the basis of receptive fields for neurons and are essential for the wiring of the nervous system. The cellular and molecular mechanisms of dendritic morphogenesis have been an intensely studied area. In this review, we summarize the major experimental systems that have contributed to our understandings of dendritic development as well as the intrinsic and extrinsic mechanisms that instruct the neurons to form cell type-specific dendritic arbors. PMID:25386991

  5. Monocyte-derived dendritic cells

    Kuhn, Sabine; Ronchese, Franca

    2013-01-01

    The elicitation of efficient antitumor immune responses requires the optimal activation of tumor-associated dendritic cells (DCs). Our comparison of the effect of various immunostimulatory treatments on DCs revealed that the best predictor of the success of immunotherapy is not the activation of existing DC populations, but the appearance of a population of monocyte-derived DC in tumor-draining lymph nodes.

  6. Fast generation of dendritic cells

    Kvistborg, P; Bøgh, Marie; Claesson, M H; Pedersen, A W

    2009-01-01

    Dendritic cells (DC) are potent antigen presenting cells capable of inducing immune responses. DC are widely used as vaccine adjuvant in experimental clinical settings. DC-based vaccines are normally generated using a standard 8day DC protocol (SDDC). In attempts to shorten the vaccine production...

  7. Intracellular spermine prevents acid-induced uncoupling of Cx43 gap junction channels.

    Skatchkov, Serguei N; Bukauskas, Feliksas F; Benedikt, Jan; Inyushin, Mikhail; Kucheryavykh, Yuriy V

    2015-06-17

    Polyamines (PAs), such as spermine and spermidine, modulate the activity of numerous receptors and channels in the central nervous system (CNS) and are stored in glial cells; however, little attention has been paid to their role in the regulation of connexin (Cx)-based gap junction channels. We have previously shown that PAs facilitate diffusion of Lucifer Yellow through astrocytic gap junctions in acute brain slices; therefore, we hypothesized that spermine can regulate Cx43-mediated (as the most abundant Cx in astrocytes) gap junctional communication. We used electrophysiological patch-clamp recording from paired Novikoff cells endogenously expressing Cx43 and HeLaCx43-EGFP transfectants to study pH-dependent modulation of cell-cell coupling in the presence or absence of PAs. Our results showed (i) a higher increase in gap junctional communication at higher concentrations of cytoplasmic spermine, and (ii) that spermine prevented uncoupling of gap junctions at low intracellular pH. Taken together, we conclude that spermine enhances Cx43-mediated gap junctional communication and may preserve neuronal excitability during ischemia and trauma when pH in the brain acidifies. We, therefore, suggest a new role of spermine in the regulation of a Cx43-based network under (patho)physiological conditions. PMID:26011388

  8. Preventive and therapeutic effects of NF-kappaB inhibitor curcumin in rats colitis induced by trinitrobenzene sulfonic acid

    Yan-Ting Jian; Guo-Feng Mai; Ji-De Wang; Ya-Li Zhang; Rong-Cheng Luo; Yong-Xin Fang

    2005-01-01

    AIM: To ascertain the molecule mechanism of nuclear factor-κB (NF-κB) inhibitor curcumin preventive and therapeutic effects in rats' colitis induced by trinitrobenzene sulfonic acid (TNBS).METHODS: Sixty rats with TNBS-induced colitis weretreated with 2.0% curcumin in the diet. Thirty positive control rats were treated with 0.5% sulfasalazine (SASP).Thirty negative control rats and thirty model rats were treated with general diet. Changes of body weight together with histological scores were evaluated. Survival rates were also evaluated. Cell nuclear NF-κB activity in colonic mucosa was evaluated by using electrophoretic mobility shift assay. Cytoplasmic IκB protein in colonic mucosa was detected by using Western Blot analysis.Cytokine messenger expression in colonic tissue was assessed by using semiquantitative reverse-transcription polymerase chain reaction.RESULTS: Treatment with curcumin could prevent and treat both wasting and histopathologic signs of rats with TNBS-induced intestinal inflammation. In accordance with these findings, NF-κB activation in colonic mucosa was suppressed in the curcumin-treated groups. Degradations of cytoplasmic IκB protein in colonic mucosa were blocked by curcumin treatment. Proinfiammatory cytokine messenger RNA expression in colonic mucosa was also suppressed.CONCLUSION: This study shows that NF-κB inhibitor curcumin could prevent and improve experimental colitis in murine model with inflammatory bowel disease (IBD).The findings suggest that NF-κB inhibitor curcumin could be a potential target for the patients with IBD.

  9. A Prevention of Pre-eclampsia with the Use of Acetylsalicylic Acid and Low-molecular Weight Heparin - Molecular Mechanisms.

    Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Korzeniewski, Michal; Kimber-Trojnar, Zaneta; Patro-Malysza, Jolanta; Mierzynski, Radzisław; Przegalinska-Kałamucka, Monika; Oleszczuk, Jan

    2016-01-01

    Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA. PMID:26927215

  10. Omega-3 polyunsaturated fatty acids: Their potential role in blood pressure prevention and management

    Claudio Borghi

    2010-05-01

    Full Text Available Omega-3 polyunsaturated fatty acids (PUFAs from fish and fish oils appear to protect against coronary heart disease: their dietary intake is in fact inversely associated to cardiovascular disease morbidity/mortality in population studies. Recent evidence suggests that at least part of their heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. In fact, omega-3 PUFAs exhibit wide-ranging biological actions that include regulating both vasomotor tone and renal sodium excretion, partly competing with omega- 6 PUFAs for common metabolic enzymes and thereby decreasing the production of vasocostrincting rather than vasodilating and anti-inflammatory eicosanoids. PUFAs also reduce angiotensin- converting enzyme (ACE activity, angiotensin II formation, TGF-beta expression, enhance eNO generation and activate the parasympathetic nervous system. The final result is improved vasodilation and arterial compliance of both small and large arteries. Preliminary clinical trials involving dyslipidemic patients, diabetics and elderly subjects, as well as normotensive and hypertensive subjects confirm this working hypothesis. Future research will clarify if PUFA supplementation could improve the antihypertensive action of specific blood pressure lowering drug classes and of statins.

  11. The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats.

    Verbeke, Len; Farre, Ricard; Verbinnen, Bert; Covens, Kris; Vanuytsel, Tim; Verhaegen, Jan; Komuta, Mina; Roskams, Tania; Chatterjee, Sagnik; Annaert, Pieter; Vander Elst, Ingrid; Windmolders, Petra; Trebicka, Jonel; Nevens, Frederik; Laleman, Wim

    2015-02-01

    Bacterial translocation (BTL) drives pathogenesis and complications of cirrhosis. Farnesoid X-activated receptor (FXR) is a key transcription regulator in hepatic and intestinal bile metabolism. We studied potential intestinal FXR dysfunction in a rat model of cholestatic liver injury and evaluated effects of obeticholic acid (INT-747), an FXR agonist, on gut permeability, inflammation, and BTL. Rats were gavaged with INT-747 or vehicle during 10 days after bile-duct ligation and then were assessed for changes in gut permeability, BTL, and tight-junction protein expression, immune cell recruitment, and cytokine expression in ileum, mesenteric lymph nodes, and spleen. Auxiliary in vitro BTL-mimicking experiments were performed with Transwell supports. Vehicle-treated bile duct-ligated rats exhibited decreased FXR pathway expression in both jejunum and ileum, in association with increased gut permeability through increased claudin-2 expression and related to local and systemic recruitment of natural killer cells resulting in increased interferon-γ expression and BTL. After INT-747 treatment, natural killer cells and interferon-γ expression markedly decreased, in association with normalized permeability selectively in ileum (up-regulated claudin-1 and occludin) and a significant reduction in BTL. In vitro, interferon-γ induced increased Escherichia coli translocation, which remained unaffected by INT-747. In experimental cholestasis, FXR agonism improved ileal barrier function by attenuating intestinal inflammation, leading to reduced BTL and thus demonstrating a crucial protective role for FXR in the gut-liver axis. PMID:25592258

  12. Characterization of Green Liquor Dregs, Potentially Useful for Prevention of the Formation of Acid Rock Drainage

    Maria Mäkitalo

    2014-04-01

    Full Text Available Using alternative materials such as residual products from other industries to mitigate the negative effects of acid rock drainage would simultaneously solve two environmental problems. The main residual product still landfilled by sulphate paper mills is the alkaline material green liquor dregs (GLD. A physical, mineralogical and chemical characterization of four batches of GLD was carried out to evaluate the potential to use it as a sealing layer in the construction of dry covers on sulphide-bearing mine waste. GLD has relatively low hydraulic conductivity (10−8 to 10−9 m/s, a high water retention capacity (WRC and small particle size. Whilst the chemical and mineralogical composition varied between the different batches, these variations were not reflected in properties such as hydraulic conductivity and WRC. Due to relatively low trace element concentrations, leaching of contaminants from the GLD is not a concern for the environment. However, GLD is a sticky material, difficult to apply on mine waste deposits and the shear strength is insufficient for engineering applications. Therefore, improving the mechanical properties is necessary. In addition, GLD has a high buffering capacity indicating that it could act as an alkaline barrier. Once engineering technicalities have been overcome, the long-term effectiveness of GLD should be studied, especially the effect of aging and how the sealing layer would be engineered in respect to topography and climatic conditions.

  13. Salicylic acid reduces napropamide toxicity by preventing its accumulation in rapeseed (Brassica napus L.).

    Cui, Jing; Zhang, Rui; Wu, Guo Lin; Zhu, Hong Mei; Yang, Hong

    2010-07-01

    Napropamide is a widely used herbicide for controlling weeds in crop production. However, extensive use of the herbicide has led to its accumulation in ecosystems, thus causing toxicity to crops and reducing crop production and quality. Salicylic acid (SA) plays multiple roles in regulating plant adaptive responses to biotic and environmental stresses. However, whether SA regulates plant response to herbicides (or pesticides) was unknown. In this study, we investigated the effect of SA on herbicide napropamide accumulation and biological processes in rapeseed (Brassica napus). Plants exposed to 8 mg kg(-1) napropamide showed growth stunt and oxidative damage. Treatment with 0.1 mM SA improved growth and reduced napropamide levels in plants. Treatment with SA also decreased the abundance of O (2) (-.) and H(2)O(2) as well as activities of superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX), and increased activities of guaiacol peroxidase (POD) and glutathione-S-transferase (GST) in napropamide-exposed plants. Analysis of SOD, CAT, and POD activities using nondenaturing polyacrylamide gel electrophoresis (PAGE) confirmed the results. These results may help to understand how SA regulates plant response to organic contaminants and provide a basis to control herbicide/pesticide contamination in crop production. PMID:19967348

  14. Comparative stability of the bioresorbable ferric crosslinked hyaluronic acid adhesion prevention solutions.

    Luu, Hoan-My Do; Chen, Angela; Isayeva, Irada S

    2013-08-01

    The Intergel® ferric crosslinked hyaluronate (FeHA) adhesion prevention solution (APS) (FDA) is associated with serious post-operative complications (Henley, http://www.lawyersandsettlements.com/features/gynecare-intergel/intergel-timeline.html, 2007; FDA, 2003; Roman et al., Fertil Steril 2005, 83 Suppl 1:1113-1118; Tang et al., Ann Surg 2006;243(4):449-455; Wiseman, Fertil Steril 2006;86(3):771; Wiseman, Fertil Steril 2006;85(4):e7). This prompted us to examine the in situ stability of crosslinked HA materials to hyaluronidase lyase degradation. Variables such as ferric ionic crosslink density, HA concentration, gel geometry, and molecular weight (MW) of HA polymer were studied. Various formulations of the crosslinked "in house" [Isayeva et al., J Biomed Mater Res: Part B - Appl Biomater 2010, 95B (1):9-18] FeHA (0.5%, w/v; 30, 50, 90% crosslinked), the Intergel® FeHA (0.5%, w/v; 90%), and the non-crosslinked HA (0.05-0.5%, w/v) were degraded at a fixed activity of hyaluronidase lyase from Streptomyces hyalurolyticus (Hyase) at 37°C over time according to the method [Payan et al., J Chrom B: Biomed Sci Appl 1991;566(1):9-18]. Under our conditions, the data show that the crosslink density affects degradation the most, followed by HA concentration and then gel geometry. We found that MW has no effect. Our results are one possible explanation of the observations that the Intergel® FeHA APS (0.5%, w/v; 90%) material persisted an order of magnitude longer than expected [t1/2 = 500 hrs vs. t1/2 = 50 hrs (FDA; Johns et al., Fertil Steril 1997;68(1):37-42)]. These data also demonstrate the sensitivity of the in vitro hyaluronidase assay to predict the in situ stability of crosslinked HA medical products as previously reported [Sall et al., Polym Degrad Stabil 2007;92(5):915-919]. PMID:23559362

  15. Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions.

    Zhu, Li; Yang, Zhong-Cheng; Li, Ao; Cheng, De-Chang

    2000-02-01

    AIM:To investigate the changes of gastric acid production and its mechanism in shock period of severe burn in rats.METHODS:A rat model with 30% TBSA full thickness burn injury was employed and the gastric acid production,together with gastric mucosal blood flow (GMBF) and energy charge (EC) were measured serially within 48h postburn.RESULTS:The gastric acid production in the acute shock period was markedly inhibited after severe burn injury.At the 3rd h postburn,the gastric juice volume, total acidity and acid output were already significantly decreased (P anti-acid drugs during burn shock period was unreasonable in some respects. Therefore, taking effective measures to improve gastric mucosal blood perfusion as early as possible postburn might be more preferable for the AGML prevention and treatment. PMID:11819529

  16. Autocrine action of BDNF on dendrite development of adult-born hippocampal neurons.

    Wang, Liang; Chang, Xingya; She, Liang; Xu, Duo; Huang, Wei; Poo, Mu-ming

    2015-06-01

    Dendrite development of newborn granule cells (GCs) in the dentate gyrus of adult hippocampus is critical for their incorporation into existing hippocampal circuits, but the cellular mechanisms regulating their dendrite development remains largely unclear. In this study, we examined the function of brain-derived neurotrophic factor (BDNF), which is expressed in adult-born GCs, in regulating their dendrite morphogenesis. Using retrovirus-mediated gene transfection, we found that deletion and overexpression of BDNF in adult-born GCs resulted in the reduction and elevation of dendrite growth, respectively. This effect was mainly due to the autocrine rather than paracrine action of BDNF, because deletion of BDNF only in the newborn GCs resulted in dendrite abnormality of these neurons to a similar extent as that observed in conditional knockout (cKO) mice with BDNF deleted in the entire forebrain. Furthermore, selective expression of BDNF in adult-born GCs in BDNF cKO mice fully restored normal dendrite development. The BDNF autocrine action was also required for the development of normal density of spines and normal percentage of spines containing the postsynaptic marker PSD-95, suggesting autocrine BDNF regulation of synaptogenesis. Furthermore, increased dendrite growth of adult-born GCs caused by voluntary exercise was abolished by BDNF deletion specifically in these neurons and elevated dendrite growth due to BDNF overexpression in these neurons was prevented by reducing neuronal activity with coexpression of inward rectifier potassium channels, consistent with activity-dependent autocrine BDNF secretion. Therefore, BDNF expressed in adult-born GCs plays a critical role in dendrite development by acting as an autocrine factor. PMID:26041908

  17. Secondary prevention of heart disease – knowledge among cardiologists and Ω-3 (Omega-3) fatty acid prescribing behaviors in Karachi, Pakistan

    Ravasia Wasik F; Hanif Hashim M; Taqui Ather M; Shoukat Sana; Gowani Saqib A; Qadri Zeeshan; Dhakam Sajid H

    2009-01-01

    Abstract Background The use of omega-3 fatty acids is a currently proven strategy for secondary prevention of heart disease. The prescription practices for this important nutraceutical is not currently known. It is imperative to assess the knowledge of cardiologists regarding the benefits of omega-3 fatty acids and to determine the frequency of its prescription. The aim of the study was to determine the practices and associations of dietary fish prescribing among cardiologists of Karachi and ...

  18. Microtubule nucleation and organization in dendrites.

    Delandre, Caroline; Amikura, Reiko; Moore, Adrian W

    2016-07-01

    Dendrite branching is an essential process for building complex nervous systems. It determines the number, distribution and integration of inputs into a neuron, and is regulated to create the diverse dendrite arbor branching patterns characteristic of different neuron types. The microtubule cytoskeleton is critical to provide structure and exert force during dendrite branching. It also supports the functional requirements of dendrites, reflected by differential microtubule architectural organization between neuron types, illustrated here for sensory neurons. Both anterograde and retrograde microtubule polymerization occur within growing dendrites, and recent studies indicate that branching is enhanced by anterograde microtubule polymerization events in nascent branches. The polarities of microtubule polymerization events are regulated by the position and orientation of microtubule nucleation events in the dendrite arbor. Golgi outposts are a primary microtubule nucleation center in dendrites and share common nucleation machinery with the centrosome. In addition, pre-existing dendrite microtubules may act as nucleation sites. We discuss how balancing the activities of distinct nucleation machineries within the growing dendrite can alter microtubule polymerization polarity and dendrite branching, and how regulating this balance can generate neuron type-specific morphologies. PMID:27097122

  19. Phase field modeling of dendritic coarsening during isothermal

    Zhang Yutuo

    2011-08-01

    Full Text Available Dendritic coarsening in Al-2mol%Si alloy during isothermal solidification at 880K was investigated by phase field modeling. Three coarsening mechanisms operate in the alloy: (a melting of small dendrite arms; (b coalescence of dendrites near the tips leading to the entrapment of liquid droplets; (c smoothing of dendrites. Dendrite melting is found to be dominant in the stage of dendritic growth, whereas coalescence of dendrites and smoothing of dendrites are dominant during isothermal holding. The simulated results provide a better understanding of dendrite coarsening during isothermal solidification.

  20. Mnemonic Functions for Nonlinear Dendritic Integration in Hippocampal Pyramidal Circuits.

    Kaifosh, Patrick; Losonczy, Attila

    2016-05-01

    We present a model for neural circuit mechanisms underlying hippocampal memory. Central to this model are nonlinear interactions between anatomically and functionally segregated inputs onto dendrites of pyramidal cells in hippocampal areas CA3 and CA1. We study the consequences of such interactions using model neurons in which somatic burst-firing and synaptic plasticity are controlled by conjunctive processing of these separately integrated input pathways. We find that nonlinear dendritic input processing enhances the model's capacity to store and retrieve large numbers of similar memories. During memory encoding, CA3 stores heavily decorrelated engrams to prevent interference between similar memories, while CA1 pairs these engrams with information-rich memory representations that will later provide meaningful output signals during memory recall. While maintaining mathematical tractability, this model brings theoretical study of memory operations closer to the hippocampal circuit's anatomical and physiological properties, thus providing a framework for future experimental and theoretical study of hippocampal function. PMID:27146266

  1. Dendrite-Free Lithium Deposition via Self-Healing Electrostatic Shield Mechanism

    Ding, Fei; Xu, Wu; Graff, Gordon L.; Zhang, Jian; Sushko, Maria L.; Chen, Xilin; Shao, Yuyan; Engelhard, Mark H.; Nie, Zimin; Xiao, Jie; Liu, Xingjiang; Sushko, P. V.; Liu, Jun; Zhang, Jiguang

    2013-02-28

    Lithium metal batteries are called the “holy grail” of energy storage systems. However, lithium dendrite growth in these batteries has prevented their practical applications in the last 40 years. Here we show a novel mechanism which can fundamentally change the dendritic morphology of lithium deposition. A low concentration of the second cations (including ions of cesium, rubidium, potassium, and strontium) exhibits an effective reduction potential lower than the standard reduction potential of lithium ions when the chemical activities of these second cations are much lower than that of lithium ions. During lithium deposition, these second cations will form a self-healing electrostatic shield around the initial tip of lithium whenever it is formed. This shield will repel the incoming lithium ions and force them to deposit in the smoother region of the anode so a dendrite-free film is obtained. This mechanism is effective on dendrite prevention in both lithium metal and lithium ion batteries. They may also prevent dendrite growth in other metal batteries and have transformational impact on the smooth deposition in general electrodeposition processes.

  2. Comparative evaluation between ascorbic acid and N-acetyl cysteine for preventing tourniquet induced ischaemic reperfusion injury during lower limb surgery, a randomized controlled trial

    Mahmoud Hassan Mohamed

    2016-01-01

    Conclusion: Both N-acetyl cysteine and ascorbic acid reduce post-deflation increase in blood levels of markers of oxidative stress and markers of systemic inflammation and thus both are beneficial in preventing post-tourniquet deflation ischemic reperfusion injury in lower limb surgery.

  3. Unsaturated compounds induce up-regulation of CD86 on dendritic cells in the in vitro sensitization assay LCSA.

    Frohwein, Thomas Armin; Sonnenburg, Anna; Zuberbier, Torsten; Stahlmann, Ralf; Schreiner, Maximilian

    2016-04-01

    Unsaturated compounds are known to cause false-positive reactions in the local lymph node assay (LLNA) but not in the guinea pig maximization test. We have tested a panel of substances (succinic acid, undecylenic acid, 1-octyn-3-ol, fumaric acid, maleic acid, linoleic acid, oleic acid, alpha-linolenic acid, squalene, and arachidonic acid) in the loose-fit coculture-based sensitization assay (LCSA) to evaluate whether unspecific activation of dendritic cells is a confounder for sensitization testing in vitro. Eight out of 10 tested substances caused significant up-regulation of CD86 on dendritic cells cocultured with keratinocytes and would have been classified as sensitizers; only succinic acid was tested negative, and squalene had to be excluded from data analysis due to poor solubility in cell culture medium. Based on human data, only undecylenic acid can be considered a true sensitizer. The true sensitizing potential of 1-octyn-3-ol is uncertain. Fumaric acid and its isomer maleic acid are not known as sensitizers, but their esters are contact allergens. A group of 18- to 20-carbon chain unsaturated fatty acids (linoleic acid, oleic acid, alpha-linolenic acid, and arachidonic acid) elicited the strongest reaction in vitro. This is possibly due to the formation of pro-inflammatory lipid mediators in the cell culture causing nonspecific activation of dendritic cells. In conclusion, both the LLNA and the LCSA seem to provide false-positive results for unsaturated fatty acids. The inclusion of T cells in dendritic cell-based in vitro sensitization assays may help to eliminate false-positive results due to nonspecific dendritic cell activation. This would lead to more accurate prediction of sensitizers, which is paramount for consumer health protection and occupational safety. PMID:25975990

  4. Prevention of bone growth defects, increased bone resorption and marrow adiposity with folinic acid in rats receiving long-term methotrexate.

    Chia-Ming Fan

    Full Text Available The underlying pathophysiology for bone growth defects in paediatric cancer patients receiving high dose methotrexate chemotherapy remains unclear and currently there are no standardized preventative treatments for patients and survivors. Using a model in young rats, we investigated damaging effects of long-term treatment with methotrexate on growth plate and metaphyseal bone, and the potential protective effects of antidote folinic acid. This study demonstrated that chronic folinic acid supplementation can prevent methotrexate-induced chondrocyte apoptosis and preserve chondrocyte columnar arrangement and number in the growth plate. In the metaphysis, folinic acid supplementation can preserve primary spongiosa heights and secondary spongiosa trabecular volume by preventing osteoblasts from undergoing apoptosis and suppressing methotrexate-induced marrow adiposity and osteoclast formation. Systemically, plasma of folinic acid supplemented rats, in comparison to plasma from rats treated with MTX alone, contained a significantly lower level of IL-1β and suppressed osteoclast formation in vitro in normal bone marrow cells. The importance of IL-1β in supporting plasma-induced osteoclast formation was confirmed as the presence of an anti-IL-1β neutralizing antibody attenuated the ability of the plasma (from MTX-treated rats in inducing osteoclast formation. Findings from this study suggest that folinic acid supplementation during chronic methotrexate treatment can alleviate growth plate and metaphyseal damages and therefore may be potentially useful in paediatric patients who are at risk of skeletal growth suppression due to chronic methotrexate chemotherapy.

  5. Drosophila Sensory Neurons Require Dscam for Dendritic Self Avoidance and Proper Dendritic Field Organization

    Soba, Peter; Zhu, Sijun; Emoto, Kazuo; Younger, Susan; Yang, Shun-Jen; Yu, Hung-Hsiang; Lee, Tzumin; Jan, Lily Yeh; Jan, Yuh-Nung

    2007-01-01

    A neuron’s dendrites typically do not cross one another. This intrinsic self-avoidance mechanism ensures unambiguous processing of sensory or synaptic inputs. Moreover, some neurons respect the territory of others of the same type, a phenomenon known as tiling. Different types of neurons, however, often have overlapping dendritic fields. We found that Down’s syndrome Cell Adhesion Molecule (Dscam) is required for dendritic self-avoidance of all four classes of Drosophila dendritic arborizatio...

  6. Homophilic Dscam interactions control complex dendrite morphogenesis

    Michael E Hughes; Bortnick, Rachel; Tsubouchi, Asako; Bäumer, Philipp; Kondo, Masahiro; Uemura, Tadashi; Schmucker, Dietmar

    2007-01-01

    The morphogenesis of complex dendritic fields requires highly specific patterning and dendrite-dendrite recognition mechanisms. Alternative splicing of the Drosophila cell surface receptor Dscam results in up to 38,016 different receptor isoforms and in vitro binding studies suggested that sequence variability in immunoglobulin-like ecto-domains determines the specificity of strictly homophilic interactions. We report that diverse Dscam receptors play an important role in controlling cell-int...

  7. Prevention and repair of ''end grain corrosion'' of Type 347 stainless steel in hot nitric acid using laser surface remelting

    Operational experience in the original nuclear fuel reprocessing plant at Sellafield in the United Kingdom showed that in very corrosive situations, 347 stainless steel could suffer from preferential attack on tubes, plates and forgings in a direction parallel to the hot working direction. This became known as ''end grain'' corrosion. The key reason that ''end grain'' attack occurs is believed to be due to regions of impurity segregation associated with stringer inclusions of Mn 5 elongated in the rolling direction during the rolling operation. In hot nitric acid environments the Mn5 stringers dissolve quickly and the impurity regions are also susceptible to attack. Investigations are reported into the effectiveness of laser surface remelting as a means of refining and homogenising the microstructure and leading to the uniform redistribution of impurities. Niobium stabilized 347 stainless steel was used in the experiments. The results show that laser surface remelting techniques are a feasible means for the repair or prevention of ''end grain'' attack. Laser surface remelting of the as-formed 347 stainless steel plate surfaces is not recommended, however, as it leads to a reduced corrosion resistance level for these areas. (13 figures, 2 tables, 12 references. (UK)

  8. Protocatechuic Acid Prevents oxLDL-Induced Apoptosis by Activating JNK/Nrf2 Survival Signals in Macrophages.

    Varì, Rosaria; Scazzocchio, Beatrice; Santangelo, Carmela; Filesi, Carmelina; Galvano, Fabio; D'Archivio, Massimo; Masella, Roberta; Giovannini, Claudio

    2015-01-01

    Protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, exerts numerous biological activities including antiapoptotic, anti-inflammatory, and antiatherosclerotic effects. Oxidised LDL have atherogenic properties by damaging arterial wall cells and inducing p53-dependent apoptosis in macrophages. This study was aimed at defining the molecular mechanism responsible for the protective effects of PCA against oxidative and proapoptotic damage exerted by oxLDL in J774 A.1 macrophages. We found that the presence of PCA in cells treated with oxLDL completely inhibited the p53-dependent apoptosis induced by oxLDL. PCA decreased oxLDL-induced ROS overproduction and in particular prevented the early increase of ROS. This decrease seemed to be the main signal responsible for maintaining the intracellular redox homeostasis hindering the activation of p53 induced by ROS, p38MAPK, and PKCδ. Consequently the overexpression of the proapoptotic p53-target genes such as p66Shc protein did not occur. Finally, we demonstrated that PCA induced the activation of JNK, which, in turn, determined the increase of nuclear Nrf2, leading to inhibition of the early ROS overproduction. We concluded that the antiapoptotic mechanism of PCA was most likely related to the activation of the JNK-mediated survival signals that strengthen the cellular antioxidant defences rather than to the PCA antioxidant power. PMID:26180584

  9. Protocatechuic Acid Prevents oxLDL-Induced Apoptosis by Activating JNK/Nrf2 Survival Signals in Macrophages

    Rosaria Varì

    2015-01-01

    Full Text Available Protocatechuic acid (PCA, one of the main metabolites of complex polyphenols, exerts numerous biological activities including antiapoptotic, anti-inflammatory, and antiatherosclerotic effects. Oxidised LDL have atherogenic properties by damaging arterial wall cells and inducing p53-dependent apoptosis in macrophages. This study was aimed at defining the molecular mechanism responsible for the protective effects of PCA against oxidative and proapoptotic damage exerted by oxLDL in J774 A.1 macrophages. We found that the presence of PCA in cells treated with oxLDL completely inhibited the p53-dependent apoptosis induced by oxLDL. PCA decreased oxLDL-induced ROS overproduction and in particular prevented the early increase of ROS. This decrease seemed to be the main signal responsible for maintaining the intracellular redox homeostasis hindering the activation of p53 induced by ROS, p38MAPK, and PKCδ. Consequently the overexpression of the proapoptotic p53-target genes such as p66Shc protein did not occur. Finally, we demonstrated that PCA induced the activation of JNK, which, in turn, determined the increase of nuclear Nrf2, leading to inhibition of the early ROS overproduction. We concluded that the antiapoptotic mechanism of PCA was most likely related to the activation of the JNK-mediated survival signals that strengthen the cellular antioxidant defences rather than to the PCA antioxidant power.

  10. The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat

    Protection by the NMDA receptor antagonist MK-801 against transient spinal cord ischemia-induced hypersensitivity was studied in rats. The spinal ischemia was initiated by vascular occlusion resulting from the interaction between the photosensitizing dye Erythrosin B and an argon laser beam. The hypersensitivity, termed allodynia, where the animals reacted by vocalization to nonnoxious mechanical stimuli in the flank area, was consistently observed during several days after induction of the ischemia. Pretreatment with MK-801 (0.1-0.5 mg/kg, iv) 10 min before laser irradiation dose dependently prevented the occurrence of allodynia. The neuroprotective effect of MK-801 was not reduced by maintaining normal body temperature during and after irradiation. There was a significant negative correlation between the delay in the administration of MK-801 after irradiation and the protective effect of the drug. Histological examination revealed slight morphological damage in the spinal cord in 38% of control rats after 1 min of laser irradiation without pretreatment with MK-801. No morphological abnormalities were observed in rats after pretreatment with MK-801 (0.5 mg/kg). The present results provide further evidence for the involvement of excitatory amino acids, through activation of the NMDA receptor, in the development of dysfunction following ischemic trauma to the spinal cord

  11. Current Review of Genetically Modified Lactic Acid Bacteria for the Prevention and Treatment of Colitis Using Murine Models.

    de Moreno de LeBlanc, Alejandra; Del Carmen, Silvina; Chatel, Jean-Marc; Miyoshi, Anderson; Azevedo, Vasco; Langella, Philippe; Bermúdez-Humarán, Luis G; LeBlanc, Jean Guy

    2015-01-01

    Inflammatory Bowel Diseases (IBD) are disorders of the gastrointestinal tract characterized by recurrent inflammation that requires lifelong treatments. Probiotic microorganisms appear as an alternative for these patients; however, probiotic characteristics are strain dependent and each probiotic needs to be tested to understand the underlining mechanisms involved in their beneficial properties. Genetic modification of lactic acid bacteria (LAB) was also described as a tool for new IBD treatments. The first part of this review shows different genetically modified LAB (GM-LAB) described for IBD treatment since 2000. Then, the two principally studied strategies are discussed (i) GM-LAB producing antioxidant enzymes and (ii) GM-LAB producing the anti-inflammatory cytokine IL-10. Different delivery systems, including protein delivery and DNA delivery, will also be discussed. Studies show the efficacy of GM-LAB (using different expression systems) for the prevention and treatment of IBD, highlighting the importance of the bacterial strain selection (with anti-inflammatory innate properties) as a promising alternative. These microorganisms could be used in the near future for the development of therapeutic products with anti-inflammatory properties that can improve the quality of life of IBD patients. PMID:26064086

  12. Precipitation dendrites in turbulent pipe flows

    Angheluta, Luiza; Hawkins, Christopher; Hammer, Øyvind; Jamtveit, Bjørn

    2013-04-01

    Surface precipitation in pipelines, as well as freezing in water pipes is of great concern in many industrial applications where scaling phenomena becomes a control problem of pipe-clogging or an efficiency reduction in transport. Flow blockage often occurs even when only a small fraction is deposited non-uniformly on the walls in the form of dendrites. Dendritic patterns are commonly encountered in surface precipitation from supersaturated solutions, e.g. calcite dendrites, as well as in solidification from undercooled liquids, e.g. freezing of water into ice dendrites. We explore the mathematical similarities between precipitation and freezing processes and, in particular, investigate the effect of fluid flow on the precipitation dendrites on pipe walls. We use a phase field approach to model surface growth coupled with a lattice Boltzmann method that simulates a channel flow at varying Reynolds number. The dendrites orientation and shape depend non-trivially on the ratio between advection and diffusion, i.e. the Peclet number, as well as the Reynolds number. Roughness induced vortices near growing dendrites at high flow rates further affect the branch splitting of dendrites. We show how the transport rate in a pipeline may depend on the different dendritic morphologies, and provide estimates for the flow conditions that correspond to most efficient transport regimes.

  13. Effect of the dendritic morphology on hot tearing of carbon steels

    Ridolfi, M. R.

    2016-03-01

    Hot tears form during solidification in the brittle region of the dendritic front. Most hot tearing criteria are based on solid and fluid mechanics, being the phenomenon strictly depending on the solid resistance to applied strains and on the liquid capability of filling the void spaces. Modelling both mechanisms implies the precise description of the dendritic morphology. To this scope, the theory of coalescence of the dendritic arms at grain boundaries of Rappaz et al. has been applied, in this work, to the columnar growth of carbon steels by means of a simple mathematical model. Depending on the alloy composition, solid bridging starts at solid fractions down to about 0.8 and up to above 0.995 (very low carbon). The morphology of the brittle region changes drastically with increasing carbon and adding other solutes. In particular, ferritic dendrites, typical of low carbon steels, tend to offer short and wide interdendritic spaces to the surrounding liquid making possible their complete filling, and few solid bridges; peritectic steels show the rise of austenite growing and bridging rapidly in the interdendritic spaces, preventing void formation; austenitic dendrites form long and narrow interdendritic spaces difficult to reach for the liquid and with a lot of solid bridges. Sulphur addition mainly acts in delaying the coalescence end, more markedly in ferritic dendrites.

  14. High mitochondrial respiration and glycolytic capacity represent a metabolic phenotype of human tolerogenic dendritic cells.

    Malinarich, Frano; Duan, Kaibo; Hamid, Raudhah Abdull; Bijin, Au; Lin, Wu Xue; Poidinger, Michael; Fairhurst, Anna-Marie; Connolly, John E

    2015-06-01

    Human dendritic cells (DCs) regulate the balance between immunity and tolerance through selective activation by environmental and pathogen-derived triggers. To characterize the rapid changes that occur during this process, we analyzed the underlying metabolic activity across a spectrum of functional DC activation states, from immunogenic to tolerogenic. We found that in contrast to the pronounced proinflammatory program of mature DCs, tolerogenic DCs displayed a markedly augmented catabolic pathway, related to oxidative phosphorylation, fatty acid metabolism, and glycolysis. Functionally, tolerogenic DCs demonstrated the highest mitochondrial oxidative activity, production of reactive oxygen species, superoxide, and increased spare respiratory capacity. Furthermore, assembled, electron transport chain complexes were significantly more abundant in tolerogenic DCs. At the level of glycolysis, tolerogenic and mature DCs showed similar glycolytic rates, but glycolytic capacity and reserve were more pronounced in tolerogenic DCs. The enhanced glycolytic reserve and respiratory capacity observed in these DCs were reflected in a higher metabolic plasticity to maintain intracellular ATP content. Interestingly, tolerogenic and mature DCs manifested substantially different expression of proteins involved in the fatty acid oxidation (FAO) pathway, and FAO activity was significantly higher in tolerogenic DCs. Inhibition of FAO prevented the function of tolerogenic DCs and partially restored T cell stimulatory capacity, demonstrating their dependence on this pathway. Overall, tolerogenic DCs show metabolic signatures of increased oxidative phosphorylation programing, a shift in redox state, and high plasticity for metabolic adaptation. These observations point to a mechanism for rapid genome-wide reprograming by modulation of underlying cellular metabolism during DC differentiation. PMID:25917094

  15. Chebulic acid prevents hepatic fibrosis induced by advanced glycation end-products in LX-2 cell by modulating Nrf2 translocation via ERK pathway.

    Koo, Yun-Chang; Pyo, Min Cheol; Nam, Mi-Hyun; Hong, Chung-Oui; Yang, Sung-Yong; Lee, Kwang-Won

    2016-08-01

    Advanced glycation end-products (AGEs) are formed during normal aging, and at an accelerated rate in metabolic syndrome patients. Nonalcoholic steatohepatitis (NASH) can be caused by the AGEs in plasma, while glyceraldehyde-derived AGEs (glycer-AGEs) are significantly higher in the serum of NASH patients. In this study, we investigated the molecular mechanisms of chebulic acid, isolated from Terminalia chebula Retz., in the inhibition of glycer-AGEs induced production of reactive oxygen species (ROS) and collagen accumulation using the LX-2 cell line. Chebulic acid significantly inhibited the induction of ROS and accumulation of collagen proteins by glycer-AGEs. ERK phosphorylation and total nuclear factor E2-related factor 2 (Nrf2) protein expression were induced by chebulic acid in a dose-dependent manner. Chebulic acid was also found to induce translocation of Nrf2 into the nucleus, which was attenuated by inhibition of ERK phosphorylation through treatment with PD98059. Following translocation of Nrf2, chebulic acid induced the protein expressions of catalytic subunit of γ-glutamylcysteine synthetase and glutathione synthesis. Collagen accumulation was also significantly reduced by chebulic acid treatment. The observed effects of chebulic acid were all inhibited by PD98059 treatment. Taken together, these results suggest that chebulic acid prevents the glycer-AGEs-induced ROS formation of LX-2 cells and collagen accumulation by ERK-phosphorylation-mediated Nrf2 nuclear translocation, which causes upregulation of antioxidant protein production. PMID:27021876

  16. HspB5/αB-crystallin increases dendritic complexity and protects the dendritic arbor during heat shock in cultured rat hippocampal neurons.

    Bartelt-Kirbach, Britta; Moron, Margarethe; Glomb, Maximilian; Beck, Clara-Maria; Weller, Marie-Pascale; Golenhofen, Nikola

    2016-10-01

    The small heat shock protein ΗspΒ5 (αB-crystallin) exhibits generally cytoprotective functions and possesses powerful neuroprotective capacity in the brain. However, little is known about the mode of action of ΗspΒ5 or other members of the HspB family particularly in neurons. To get clues of the neuronal function of HspBs, we overexpressed several HspBs in cultured rat hippocampal neurons and investigated their effect on neuronal morphology and stress resistance. Whereas axon length and synapse density were not affected by any HspB, dendritic complexity was enhanced by HspB5 and, to a lesser extent, by HspB6. Furthermore, we could show that this process was dependent on phosphorylation, since a non-phosphorylatable mutant of HspB5 did not show this effect. Rarefaction of the dendritic arbor is one hallmark of several neurodegenerative diseases. To investigate if HspB5, which is upregulated at pathophysiological conditions, might be able to protect dendrites during such situations, we exposed HspB5 overexpressing neuronal cultures to heat shock. HspB5 prevented heat shock-induced rarefaction of dendrites. In conclusion, we identified regulation of dendritic complexity as a new function of HspB5 in hippocampal neurons. PMID:27085702

  17. A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

    Alai, Milind; Lin, Wen Jen

    2013-01-01

    The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration. PMID:23294453

  18. The uptake in the pancreatic islets of nicotimamide, nicotinic acid and tryptophan and their ability to prevent streptozotocin diabetes in mice

    The uptake of the nicotinamide adenine dinucleotide (NAD)-precursors nicotinamide, nicotinic acid and tryptophan in the pancreatic islets of mice was studied by use of autoradio-graphical methods. The ability of these substances to prevent streptozotocin diabetes was studied in the same species. It was found that only nicotinamide was strongly accumulated in the pancreatic islets and nicotinamide was also the only NAD-precursor which protected against the streptozotocin diabetes. Apparently there is a relationship between the ability of the NAD-precursors to be taken up in the pancreatic islets and their ability to prevent streptozotocin diabetes. (author)

  19. Renal dendritic cells: an update

    Velázquez, Peter; Dustin, Michael L.; Peter J Nelson

    2009-01-01

    Discovery into the role of renal dendritic cells (rDCs) in health and disease of the kidney is rapidly accelerating. Progress in deciphering DC precursors and the heterogeneity of monocyte subsets in mice and humans are providing insights into the biology of rDCs. Recent findings have extended knowledge of the origins, anatomy, and function of the rDC network at steady-state and during periods of injury to the renal parenchyma. This brief review highlights these new findings and provides an u...

  20. Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections.

    Flores, Claudia; Degoutin, Stephanie; Chai, Feng; Raoul, Gwenael; Hornez, Jean-Chritophe; Martel, Bernard; Siepmann, Juergen; Ferri, Joel; Blanchemain, Nicolas

    2016-07-01

    Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60μm, allowing for incorporation inside the macropores (100μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25-30days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions. PMID:27127034

  1. Vertical solidification of dendritic binary alloys

    Heinrich, J. C.; Felicelli, S.; Poirier, D. R.

    1991-01-01

    Three numerical techniques are employed to analyze the influence of thermosolutal convection on defect formation in directionally solidified (DS) alloys. The finite-element models are based on the Boussinesq approximation and include the plane-front model and two plane-front models incorporating special dendritic regions. In the second model the dendritic region has a time-independent volume fraction of liquid, and in the last model the dendritic region evolves as local conditions dictate. The finite-element models permit the description of nonlinear thermosolutal convection by treating the dendritic regions as porous media with variable porosities. The models are applied to lead-tin alloys including DS alloys, and severe segregation phenomena such as freckles and channels are found to develop in the DS alloys. The present calculations and the permeability functions selected are shown to predict behavior in the dendritic regions that qualitatively matches that observed experimentally.

  2. Early events in axon/dendrite polarization.

    Cheng, Pei-lin; Poo, Mu-ming

    2012-01-01

    Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure. PMID:22715881

  3. Prevention of methionine and ammonia-induced coma by intravenous infusion of a branched chain amino acid solution to rats with liver injury.

    Shiota,Tetsuya

    1984-10-01

    Full Text Available The prevention of hepatic encephalopathy by the intravenous infusion of a branched chain amino acid (BCAA-enriched solution was investigated in methionine and ammonium acetate-treated rats whose liver was already injured with carbon tetrachloride. A BCAA-enriched solution protected the rats from entering a coma. The brain BCAA contents became higher, and the brain methionine and tyrosine levels and the ratio of glutamine to glutamic acid in the brain diminished after administering the BCAA-enriched solution.

  4. Dendritic Cells in the Cancer Microenvironment

    Yang Ma, Galina V. Shurin, Zhu Peiyuan, Michael R. Shurin

    2013-01-01

    Full Text Available The complexity of the tumor immunoenvironment is underscored by the emergence and discovery of different subsets of immune effectors and regulatory cells. Tumor-induced polarization of immune cell differentiation and function makes this unique environment even more intricate and variable. Dendritic cells (DCs represent a special group of cells that display different phenotype and activity at the tumor site and exhibit differential pro-tumorigenic and anti-tumorigenic functions. DCs play a key role in inducing and maintaining the antitumor immunity, but in the tumor environment their antigen-presenting function may be lost or inefficient. DCs might be also polarized into immunosuppressive/tolerogenic regulatory DCs, which limit activity of effector T cells and support tumor growth and progression. Although various factors and signaling pathways have been described to be responsible for abnormal functioning of DCs in cancer, there are still no feasible therapeutic modalities available for preventing or reversing DC malfunction in tumor-bearing hosts. Thus, better understanding of DC immunobiology in cancer is pivotal for designing novel or improved therapeutic approaches that will allow proper functioning of DCs in patients with cancer.

  5. Engineering crystals of dendritic molecules.

    Lukin, Oleg; Schubert, Dirk; Müller, Claudia M; Schweizer, W Bernd; Gramlich, Volker; Schneider, Julian; Dolgonos, Grygoriy; Shivanyuk, Alexander

    2009-07-01

    A detailed single-crystal X-ray study of conformationally flexible sulfonimide-based dendritic molecules with systematically varied molecular architectures was undertaken. Thirteen crystal structures reported in this work include 9 structures of the second-generation dendritic sulfonimides decorated with different aryl groups, 2 compounds bearing branches of both second and first generation, and 2 representatives of the first generation. Analysis of the packing patterns of 9 compounds bearing second-generation branches shows that despite their lack of strong directive functional groups there is a repeatedly reproduced intermolecular interaction mode consisting in an anchor-type packing of complementary second-generation branches of neighbouring molecules. The observed interaction tolerates a wide range of substituents in meta- and para-positions of the peripheral arylsulfonyl rings. Quantum chemical calculations of the molecule-molecule interaction energies agree at the qualitative level with the packing preferences found in the crystalline state. The calculations can therefore be used as a tool to rationalize and predict molecular structures with commensurate and non-commensurate branches for programming of different packing modes in crystal. PMID:19549870

  6. Clearance of fear memory from the hippocampus through neurogenesis by omega-3 fatty acids: a novel preventive strategy for posttraumatic stress disorder?

    Matsuoka Yutaka

    2011-02-01

    Full Text Available Abstract Not only has accidental injury been shown to account for a significant health burden on all populations, regardless of age, sex and geographic region, but patients with accidental injury frequently present with the psychiatric condition of posttraumatic stress disorder (PTSD. Prevention of accident-related PTSD thus represents a potentially important goal. Physicians in the field of psychosomatic medicine and critical care medicine have the opportunity to see injured patients in the immediate aftermath of an accident. This article first briefly reviews the prevalence and associated factors of accident-related PTSD, then focuses on a conceptual model of fear memory and proposes a new, rationally hypothesized translational preventive intervention for PTSD through promoting hippocampal neurogenesis by omega-3 fatty acid supplementation. The results of an open-label pilot trial of injured patients admitted to the intensive care unit suggest that omega-3 fatty acid supplementation immediately after accidental injury can reduce subsequent PTSD symptoms.

  7. Glycochenodeoxycholic acid inhibits calcium phosphate precipitation in vitro by preventing the transformation of amorphous calcium phosphate to calcium hydroxyapatite.

    Qiu, S M; Wen, G.; Hirakawa, N; Soloway, R D; Hong, N K; Crowther, R S

    1991-01-01

    Calcium hydroxyapatite can be a significant component of black pigment gallstones. Diverse molecules that bind calcium phosphate inhibit hydroxyapatite precipitation. Because glycine-conjugated bile acids, but not their taurine counterparts, bind calcium phosphate, we studied whether glycochenodeoxycholic acid inhibits calcium hydroxyapatite formation. Glycochenodeoxycholic acid (2 mM) totally inhibited transformation of amorphous calcium phosphate microprecipitates to macroscopic crystalline...

  8. PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid -Hydroxylase (CYP4 Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease

    James P. Hardwick

    2009-01-01

    Full Text Available Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis, due to a decrease in mitochondria -oxidation with an increase in both peroxisomal -oxidation, and microsomal -oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs. How steatosis increases PPAR activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid -oxidation and -oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA, monounsaturated (MUFA, or saturated (SFA may be determined by the interplay of PPARs and HNF4 with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the -oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPAR. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid -hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA CYP4A and long-chain fatty acid (LCFA CYP4F -hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to

  9. Preventive effects of amino-acid-rich elemental diet Elental® on chemotherapy-induced oral mucositis in patients with colorectal cancer: a prospective pilot study

    Ogata, Yutaka; Ishibashi, Nobuya; Yamaguchi, Keizou; UCHIDA, SHINJI; Kamei, Hideki; Nakayama, Goichi; Hirakawa, Hiroaki; Tanigawa, Masahiko; Akagi, Yoshito

    2015-01-01

    Purpose The prospective pilot study was designed to evaluate the preventive effects of amino-acid-rich elemental diet (ED), Elental®, on chemotherapy-induced oral mucositis in patients with colorectal cancer. The factors influencing its efficacy are also investigated. Methods A total of 22 eligible patients with colorectal cancer experiencing grade 1–3 oral mucositis during treatment with fluorouracil-based chemotherapy entered the current study. Their average age was 67 years. There were 10 ...

  10. An Evaluation of a Teat Dip with Dodecyl Benzene Sulfonic Acid in Preventing Bovine Mammary Gland Infection from Experimental Exposure to Streptococcus agalactiae and Staphylococcus aureus

    Barnum, D A; Johnson, R. E.; Brooks, B W

    1982-01-01

    The effectiveness of a teat dip with dodecyl benzene sulfonic acid (1.94%) for the prevention of intramammary infections was determined in cows experimentally challenged with Streptococcus agalactiae and Staphylococcus aureus. The infection rates with Streptococcus agalactiae and Staphylococcus aureus were 62.5% and 75% in undipped quarters, 12.5% and 21.5% in dipped quarters with a reduction rate of 80% and 71% respectively. The significance of some findings in relation to mastitis control a...

  11. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats

    Thewarid Berkban

    2015-06-01

    Full Text Available The effect of ellagic acid on oxidative stress and hypertension induced by Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day for five weeks. L-NAME induced high systolic blood pressure (SBP and increased heart rate (HR, hindlimb vascular resistance (HVR and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability.

  12. Role of amino acids and vitamins in prevention of and rapid recovery from fatigue in the officers and soldiers at high altitude

    Wen HUANG

    2012-01-01

    Full Text Available Objective  To explore the role of amino acids and vitamins in the prevention of and recovery from the fatigue related to military operation in the officers and soldiers at high altitude. Methods  The participants were 100 officers and soldiers, whose Modified Fatigue Rating Scale (MFIS scores were >21 points. The participants were randomly divided into three groups: capsule, placebo, and granules. Amino acids capsule (8 kinds of essential amino acids and 11 kinds of vitamins were contained, placebo, or amino acid-fructose beverage was given to respective group for 14 days continuously. The 3000-m running performance of the officers and soldiers stationed on a plateau was measured on the first and 14th days. The maximal grip strength of the right hand, fist-making times per minute, and the height reaching by the hand after three-step run-up for the same candidate were observed before and after fatigue loading (3000-m running. The blood levels of lactic acid and urea nitrogen of the candidates were measured after fatigue loading on the first and the 14th days. Results  The 3000-m running performance of officers and soldiers in the capsule and granules groups on the 14th day were better than that of the first day (PP>0.05. The difference between the capsule and the granules groups in grip strength, fist-making times per minute, and hand reaching height on the 14th day were obviously lower than that on the first day (PP>0.05. The blood levels of lactic acid and urea nitrogen in the capsule and granules groups on the 14th day were lower than that on the first day (PP>0.05. Conclusions  Amino acids and vitamins preparations can obviously improve the military performance capacity of officers and soldiers stationed on the plateau. Similarly, they can effectively prevent the lowering of jumping ability and grip strength caused by military fatigue. Therefore, amino acids and vitamins preparations play an important role in the prevention of and rapid

  13. Distinctive PSA-NCAM and NCAM Hallmarks in Glutamate-Induced Dendritic Atrophy and Synaptic Disassembly

    Podestá, María Fernanda; Yam, Patricia; Codagnone, Martín Gabriel; Uccelli, Nonthué Alejandra; Colman, David; Reinés, Analía

    2014-01-01

    Dendritic and synapse remodeling are forms of structural plasticity that play a critical role in normal hippocampal function. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) participate in neurite outgrowth and synapse formation and plasticity. However, it remains unclear whether they contribute to dendritic retraction and synaptic disassembly. Cultured hippocampal neurons exposed to glutamate (5 µM) showed a reduced MAP-2 (+) area in the absence of neuronal death 24 h after the insult. Concomitantly, synapse loss, revealed by decreased synaptophysin and post-synaptic density-95 cluster number and area, together with changes in NCAM and PSA-NCAM levels were found. Dendritic atrophy and PSA-NCAM reduction proved NMDA-receptor dependent. Live-imaging experiments evidenced dendritic atrophy 4 h after the insult; this effect was preceded by smaller NCAM clusters (1 h) and decreased surface and total PSA-NCAM levels (3 h). Simultaneously, total NCAM cluster number and area remained unchanged. The subsequent synapse disassembly (6 h) was accompanied by reductions in total NCAM cluster number and area. A PSA mimetic peptide prevented both the dendritic atrophy and the subsequent synaptic changes (6 h) but had no effect on the earliest synaptic remodeling (3 h). Thus, NCAM-synaptic reorganization and PSA-NCAM level decrease precede glutamate-induced dendritic atrophy, whereas the NCAM level reduction is a delayed event related to synapse loss. Consequently, distinctive stages in PSA-NCAM/NCAM balance seem to accompany glutamate-induced dendritic atrophy and synapse loss. PMID:25279838

  14. Dendritic cells in lung immunopathology.

    Cook, Peter C; MacDonald, Andrew S

    2016-07-01

    Dendritic cells (DCs) lie at the heart of the innate immune system, specialised at recognising danger signals in many forms including foreign material, infection or tissue damage and initiating powerful adaptive immune and inflammatory responses. In barrier sites such as the lung, the instrumental role that DCs play at the interface between the environment and the host places them in a pivotal position in determining the severity of inflammatory disease. The past few years has seen a significant increase in our fundamental understanding of the subsets of DCs involved in pulmonary immunity, as well as the mechanisms by which they are activated and which they may use to coordinate downstream inflammation and pathology. In this review, we will summarise current understanding of the multi-faceted role that DCs play in the induction, maintenance and regulation of lung immunopathology, with an emphasis on allergic pulmonary disease. PMID:27256370

  15. Dendritic Cells for Anomaly Detection

    Greensmith, Julie; Aickelin, Uwe

    2010-01-01

    Artificial immune systems, more specifically the negative selection algorithm, have previously been applied to intrusion detection. The aim of this research is to develop an intrusion detection system based on a novel concept in immunology, the Danger Theory. Dendritic Cells (DCs) are antigen presenting cells and key to the activation of the human signals from the host tissue and correlate these signals with proteins know as antigens. In algorithmic terms, individual DCs perform multi-sensor data fusion based on time-windows. The whole population of DCs asynchronously correlates the fused signals with a secondary data stream. The behaviour of human DCs is abstracted to form the DC Algorithm (DCA), which is implemented using an immune inspired framework, libtissue. This system is used to detect context switching for a basic machine learning dataset and to detect outgoing portscans in real-time. Experimental results show a significant difference between an outgoing portscan and normal traffic.

  16. Acid stress damage of DNA is prevented by Dps binding in Escherichia coli O157:H7

    Baumler David J; Hung Kai; Jeong Kwang; Byrd Jeffrey J; Kaspar Charles W

    2008-01-01

    Abstract Background Acid tolerance in Escherichia coli O157:H7 contributes to persistence in its bovine host and is thought to promote passage through the gastric barrier of humans. Dps (DNA-binding protein in starved cells) mutants of E. coli have reduced acid tolerance when compared to the parent strain although the role of Dps in acid tolerance is unclear. This study investigated the mechanism by which Dps contributes to acid tolerance in E. coli O157:H7. Results The results from this stud...

  17. Application of citrate as a tricarboxylic acid (TCA cycle intermediate, prevents diabetic-induced heart damages in mice

    Qianqian Liang

    2016-01-01

    Conclusion: Results indicate that application of citrate, a tricarboxylic acid (TCA cycle intermediate, might alleviate cardiac dysfunction by reducing cardiac inflammation, apoptosis, and increasing cardiac EC.

  18. Syntheses, Characterization, Physical and Biological Properties of Long-chain, Water-soluble, Dendritic Amphiphiles

    Williams, André Arvin

    2008-01-01

    In this project, we have designed and synthesized a new series of long-chain, water-soluble, dendritic, anionic amphiphiles [3CAmn, RCONHC(CH2CH2COOH)3, R= CnH2n+1] to alleviate the low aqueous solubility of fatty acids. The dendritic-tricarboxlyato headgroup improves aqueous solubility and allows us to measure the intrinsic biological activity of our amphiphiles without the potential hindrance of low aqueous solubility. The aqueous solubilities of the anionic amphiphiles have been measured...

  19. DEX-1 and DYF-7 establish sensory dendrite length by anchoring dendritic tips during cell migration

    Heiman, Maxwell G.; Shaham, Shai

    2009-01-01

    Cells are devices whose structures delimit function. For example, in the nervous system, neuronal and glial shapes dictate paths of information flow. To understand how cells acquire their shapes, we examined the formation of a sense organ in C. elegans. Using time-lapse imaging, we found that sensory dendrites form by stationary anchoring of dendritic tips during cell-body migration. A genetic screen identified DEX-1 and DYF-7, extracellular proteins required for dendritic tip anchoring, whic...

  20. Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status.

    Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Magrisso, I Jack; Benoit, Stephen C; McNamara, Robert K

    2011-09-01

    This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids. PMID:22024496

  1. Dendritic Spine Pathology in Neurodegenerative Diseases.

    Herms, Jochen; Dorostkar, Mario M

    2016-05-23

    Substantial progress has been made toward understanding the neuropathology, genetic origins, and epidemiology of neurodegenerative diseases, including Alzheimer's disease; tauopathies, such as frontotemporal dementia; α-synucleinopathies, such as Parkinson's disease or dementia with Lewy bodies; Huntington's disease; and amyotrophic lateral sclerosis with dementia, as well as prion diseases. Recent evidence has implicated dendritic spine dysfunction as an important substrate of the pathogenesis of dementia in these disorders. Dendritic spines are specialized structures, extending from the neuronal processes, on which excitatory synaptic contacts are formed, and the loss of dendritic spines correlates with the loss of synaptic function. We review the literature that has implicated direct or indirect structural alterations at dendritic spines in the pathogenesis of major neurodegenerative diseases, focusing on those that lead to dementias such as Alzheimer's, Parkinson's, and Huntington's diseases, as well as frontotemporal dementia and prion diseases. We stress the importance of in vivo studies in animal models. PMID:26907528

  2. Artificial Dendritic Cells: Multi-faceted Perspectives

    Greensmith, Julie

    2009-01-01

    Dendritic cells are the crime scene investigators of the human immune system. Their function is to correlate potentially anomalous invading entities with observed damage to the body. The detection of such invaders by dendritic cells results in the activation of the adaptive immune system, eventually leading to the removal of the invader from the host body. This mechanism has provided inspiration for the development of a novel bio-inspired algorithm, the Dendritic Cell Algorithm. This algorithm processes information at multiple levels of resolution, resulting in the creation of information granules of variable structure. In this chapter we examine the multi-faceted nature of immunology and how research in this field has shaped the function of the resulting Dendritic Cell Algorithm. A brief overview of the algorithm is given in combination with the details of the processes used for its development. The chapter is concluded with a discussion of the parallels between our understanding of the human immune system a...

  3. Human monocyte-derived dendritic cells turn into foamy dendritic cells with IL-17A.

    Salvatore, Giulia; Bernoud-Hubac, Nathalie; Bissay, Nathalie; Debard, Cyrille; Daira, Patricia; Meugnier, Emmanuelle; Proamer, Fabienne; Hanau, Daniel; Vidal, Hubert; Aricò, Maurizio; Delprat, Christine; Mahtouk, Karène

    2015-06-01

    Interleukin 17A (IL-17A) is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases. In the field of immunometabolism, we have studied the impact of IL-17A on the lipid metabolism of human in vitro-generated monocyte-derived dendritic cells (DCs). Microarrays and lipidomic analysis revealed an intense remodeling of lipid metabolism induced by IL-17A in DCs. IL-17A increased 2-12 times the amounts of phospholipids, cholesterol, triglycerides, and cholesteryl esters in DCs. Palmitic (16:0), stearic (18:0), and oleic (18:ln-9c) acid were the main fatty acid chains present in DCs. They were strongly increased in response to IL-17A while their relative proportion remained unchanged. Capture of extracellular lipids was the major mechanism of lipid droplet accumulation, visualized by electron microscopy and Oil Red O staining. Besides this foamy phenotype, IL-17A induced a mixed macrophage-DC phenotype and expression of the nuclear receptor NR1H3/liver X receptor-α, previously identified in the context of atherosclerosis as the master regulator of cholesterol homeostasis in macrophages. These IL-17A-treated DCs were as competent as untreated DCs to stimulate allogeneic naive T-cell proliferation. Following this first characterization of lipid-rich DCs, we propose to call these IL-17A-dependent cells "foamy DCs" and discuss the possible existence of foamy DCs in atherosclerosis, a metabolic and inflammatory disorder involving IL-17A. PMID:25833686

  4. Acid mine drainage prevention, control and treatment technology development for the Stockett/Sand Coulee area. Topical report, March 1, 1995 - March 31, 1996

    The project was initiated to assist the State of Montana to develop a methodology to ameliorate acid mine drainage problems associated with the abandoned mines located in the Stockett/Sand Coulee area near Great Falls, Montana. Extremely acidic water is continuously discharging from abandoned coal mines in the Stockett/Sand Coulee area at an estimated rate of greater than 600 acre-feet per year (about 350 to 400 gallons per minute). Due to its extreme acidity, the water is unusable and is contaminating other water supplies. Most of the local alluvial aquifers have been contaminated, and nearly 5% of the private wells that were tested in the area during the mid-1980's showed some degree of contamination. Significant government money has been spent replacing water supplies due to the magnitude of this problem. In addition, millions of dollars have been spent trying to remediate acid mine drainage occurring in this coal field. To date, the techniques used have focused on the management and containment of mine waters, rather than designing technologies that would prevent the formation of acid mine drainage

  5. The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids

    Jun Ding

    2013-10-01

    Full Text Available Specific metabolic pathways are activated by different nutrients to adapt the organism to available resources. Although essential, these mechanisms are incompletely defined. Here, we report that medium-chain fatty acids contained in coconut oil, a major source of dietary fat, induce the liver ω-oxidation genes Cyp4a10 and Cyp4a14 to increase the production of dicarboxylic fatty acids. Furthermore, these activate all ω- and β-oxidation pathways through peroxisome proliferator activated receptor (PPAR α and PPARγ, an activation loop normally kept under control by dicarboxylic fatty acid degradation by the peroxisomal enzyme L-PBE. Indeed, L-pbe−/− mice fed coconut oil overaccumulate dicarboxylic fatty acids, which activate all fatty acid oxidation pathways and lead to liver inflammation, fibrosis, and death. Thus, the correct homeostasis of dicarboxylic fatty acids is a means to regulate the efficient utilization of ingested medium-chain fatty acids, and its deregulation exemplifies the intricate relationship between impaired metabolism and inflammation.

  6. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment.

    Oulhaj, Abderrahim; Jernerén, Fredrik; Refsum, Helga; Smith, A David; de Jager, Celeste A

    2015-01-01

    A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale, and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega-3 fatty acids) were measured. Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective. When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, B vitamins interact to slow cognitive decline. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD. PMID:26757190

  7. Weathering behaviour of overburden-coal ash blending in relation to overburden management for acid mine drainage prevention in coal surface mine

    Potentially acid forming (PAF) materials are encapsulated with non-acid forming materials (NAF) in order to prevent acid mine drainage (AMD) in surface coal mines. NAF compaction techniques with fly and bottom ashes from coal-fired power plants are used in mines with limited amounts of NAF materials. This study investigated the weathering behaviour of blended overburden and coal combustion ash in laboratory conditions. Free draining column leach tests were conducted on different blending schemes. The weathering process was simulated by spraying the samples with de-ionized water once per day. The leachates were then analyzed using X-ray diffraction and fluorescence analyses in order to identify the mineral composition of the samples over a 14 week period. Results of the study indicated that the weathering process plays a significant role in controlling infiltration rates, and may increase the capability of capping materials to prevent infiltration into PAF materials. Fly- and bottom-ash additions improved the performance of the encapsulation materials. 3 refs., 4 tabs., 2 figs.

  8. Vocal cord palsy after vincristine treatment in a child and the inefficacy of glutamic acid in the prevention of relapse: a case report

    Farruggia Piero

    2012-05-01

    Full Text Available Abstract Introduction Vincristine is an antineoplastic drug with a well known efficacy for the treatment of acute lymphoblastic leukemia and many solid tumors. No more than 20 pediatric patients with vincristine-induced vocal cord palsy have been reported, and to the best of our knowledge this is the first case where glutamic acid was administered with the aim of preventing a relapse of laryngeal dysfunction. Case presentation The larynx paralysis presented with hoarseness and stridor in a Caucasian 18-month-old girl and spontaneously resolved in about a month. In order to administer a subsequent full dose of vincristine, our patient received oral glutamic acid whose efficacy against vincristine neurological side effects has been previously reported. Conclusions Since in our patient the amino acid proved to be ineffective in the prevention of laryngeal paralysis relapse, we suggest that a dose reduction of vincristine should be preferred by oncologists as an initial approach after a case of drug-induced vocal cord palsy.

  9. Free energy and dendritic self-organisation

    Stefan J Kiebel

    2011-10-01

    Full Text Available In this paper, we pursue recent observations that, through selective dendritic filtering, single neurons respond to specific sequences of presynaptic inputs. We try to provide a principled and mechanistic account of this selectivity by applying the free energy principle to a dendrite that is immersed in its neuropil or environment. We assume that neurons self-organize to minimise a free energy bound on the self-information or surprise of presynaptic inputs that are sampled. We model this as a selective pruning of dendritic spines that are expressed on a dendritic branch. This pruning occurs when the optimized postsynaptic gain falls below a threshold. Crucially, postsynaptic gain is itself optimized with respect to free energy. Pruning suppresses free energy as the dendrite selects presynaptic signals that conform to its expectations, specified by a generative model implicit in its intracellular kinetics. Not only does this provide a principled account of how neurons organize and selectively sample the myriad of potential presynaptic inputs they are exposed to, but it also connects the optimization of elemental neuronal (dendritic processing to generic (surprise or evidence-based schemes in statistics and machine learning, such as Bayesian model selection and automatic relevance determination.

  10. Acetylsalicylic Acid Compared to Placebo in Treating High-Risk Patients With Subsolid Lung Nodules | Division of Cancer Prevention

    This randomized phase II trial studies acetylsalicylic acid compared to placebo in treating high-risk patients with subsolid lung nodules. A nodule is a growth or lump that may be malignant (cancer) or benign (not cancer). Chemoprevention is the use of drugs to keep cancer from forming or coming back. The use of acetylsalicylic acid may keep cancer from forming in patients with subsolid lung nodules. |

  11. Beyond the Role of Dietary Protein and Amino Acids in the Prevention of Diet-Induced Obesity

    Klaus J. Petzke

    2014-01-01

    Full Text Available High-protein diets have been shown to prevent the development of diet-induced obesity and can improve associated metabolic disorders in mice. Dietary leucine supplementation can partially mimic this effect. However, the molecular mechanisms triggering these preventive effects remain to be satisfactorily explained. Here we review studies showing a connection between high protein or total amino nitrogen intake and obligatory water intake. High amino nitrogen intake may possibly lower lipid storage, and prevent insulin resistance. Suggestions are made for further systematical studies to explore the relationship between water consumption, satiety, and energy expenditure. Moreover, these examinations should better distinguish between leucine-specific and unspecific effects. Research in this field can provide important information to justify dietary recommendations and strategies in promoting long-term weight loss and may help to reduce health problems associated with the comorbidities of obesity.

  12. Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism.

    Jimcy Platholi

    Full Text Available General anesthetics produce a reversible coma-like state through modulation of excitatory and inhibitory synaptic transmission. Recent evidence suggests that anesthetic exposure can also lead to sustained cognitive dysfunction. However, the subcellular effects of anesthetics on the structure of established synapses are not known. We investigated effects of the widely used volatile anesthetic isoflurane on the structural stability of hippocampal dendritic spines, a postsynaptic structure critical to excitatory synaptic transmission in learning and memory. Exposure to clinical concentrations of isoflurane induced rapid and non-uniform shrinkage and loss of dendritic spines in mature cultured rat hippocampal neurons. Spine shrinkage was associated with a reduction in spine F-actin concentration. Spine loss was prevented by either jasplakinolide or cytochalasin D, drugs that prevent F-actin disassembly. Isoflurane-induced spine shrinkage and loss were reversible upon isoflurane elimination. Thus, isoflurane destabilizes spine F-actin, resulting in changes to dendritic spine morphology and number. These findings support an actin-based mechanism for isoflurane-induced alterations of synaptic structure in the hippocampus. These reversible alterations in dendritic spine structure have important implications for acute anesthetic effects on excitatory synaptic transmission and synaptic stability in the hippocampus, a locus for anesthetic-induced amnesia, and have important implications for anesthetic effects on synaptic plasticity.

  13. N-3 polyunsaturated Fatty acids prevent diabetic retinopathy by inhibition of retinal vascular damage and enhanced endothelial progenitor cell reparative function.

    Maria Tikhonenko

    Full Text Available OBJECTIVE: The vasodegenerative phase of diabetic retinopathy is characterized by not only retinal vascular degeneration but also inadequate vascular repair due to compromised bone marrow derived endothelial progenitor cells (EPCs. We propose that n-3 polyunsaturated fatty acid (PUFA deficiency in diabetes results in activation of the central enzyme of sphingolipid metabolism, acid sphingomyelinase (ASM and that ASM represents a molecular metabolic link connecting the initial damage in the retina and the dysfunction of EPCs. RESEARCH DESIGN AND METHODS: Type 2 diabetic rats on control or docosahexaenoic acid (DHA-rich diet were studied. The number of acellular capillaries in the retinas was assessed by trypsin digest. mRNA levels of interleukin (IL-1β, IL-6, intracellular adhesion molecule (ICAM-1 in the retinas from diabetic animals were compared to controls and ASM protein was assessed by western analysis. EPCs were isolated from blood and bone marrow and their numbers and ability to form colonies in vitro, ASM activity and lipid profiles were determined. RESULTS: DHA-rich diet prevented diabetes-induced increase in the number of retinal acellular capillaries and significantly enhanced the life span of type 2 diabetic animals. DHA-rich diet blocked upregulation of ASM and other inflammatory markers in diabetic retina and prevented the increase in ASM activity in EPCs, normalized the numbers of circulating EPCs and improved EPC colony formation. CONCLUSIONS: In a type 2 diabetes animal model, DHA-rich diet fully prevented retinal vascular pathology through inhibition of ASM in both retina and EPCs, leading to a concomitant suppression of retinal inflammation and correction of EPC number and function.

  14. Omega-3 fatty acids from fish oil supplements, but not alpha-linolenic acid benefit cardiovascular disease outcomes in primary & secondary prevention studies: a systematic review

    The relationship between dietary omega-3 fatty acids and cardiovascular disease is uncertain. The published literature is replete with studies of varying methodological quality and sometimes contradictory results. The objective of this work was to conduct a systematic review and critical appraisal ...

  15. Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα.

    Zhang, Yanan; Song, Chengwei; Li, Haiou; Hou, Jingdong; Li, Dongliang

    2016-06-01

    Obesity is a risk factor for several pain syndromes and is associated with increased pain sensitivity. Evidence suggests that obesity causes the downregulation of peroxisome proliferator‑activated receptor (PPAR)α in the spinal cord, contributing to augmented peripheral edema and inflammatory hyperalgesia. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, has been shown to upregulate PPARα in the peripheral tissues of obese animals. The present study hypothesized that UA prevents augmented peripheral inflammation and inflammatory hyperalgesia in obesity by restoring downregulated spinal PPARα. The present study demonstrated that Sprague‑Dawley rats fed a high‑fat diet (HFD) for 12 weeks developed obesity and metabolic disorder. Following carrageenan injection, the HFD rats exhibited increased thermal hyperalgesia and paw edema, compared with the rats fed a low‑fat diet. Molecular investigations revealed that the HFD rats exhibited decreased PPARα activity, and exaggerated expression of inflammatory mediators and nuclear factor‑kB activity in the spinal cord in response to carrageenan. Oral administration of UA ameliorated obesity and metabolic disorder, and prevented increased thermal hyperalgesia and paw edema in the HFD rats. Additionally, UA normalized PPARα activity and inhibited the exaggerated spinal cord inflammatory response to carrageenan. Although the knockdown of spinal PPARα with small interfering RNA following the administration of UA did not alter obesity or metabolic parameters, it eradicated the beneficial effects of UA on thermal hyperalgesia and paw edema, and reversed the spinal cord inflammatory response. These results suggested that the systemic administration of UA inhibited the exaggerated spinal cord inflammatory response to peripheral inflammatory stimulation in HFD‑induced obesity by restoring downregulated spinal PPARα, preventing peripheral inflammation and inflammatory hyperalgesia. UA may be a

  16. Temporal and spatial variation in the status of acid rivers and potential prevention methods of AS soil-related leaching in peatland forestry

    Saarinen, T.

    2013-06-01

    maintenance drainage in peatland forestry on runoff water quality showed a clear risk of oxidation of sulphidic materials during dry summers. This can be prevented mainly by avoiding too deep drainage. Knowledge of the hydrochemical impacts of acidic load derived from AS soils and drained peatlands is necessary for land use planning and sustainable water management of river basins affected by these soils. (orig.)

  17. Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED study

    Rosman Johan

    2009-01-01

    Full Text Available Abstract Background Haemodialysis (HD is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF. The Primary failure rate of an AVF ranges between 20–54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF. Methods/Design The study population is adult patients with stage IV or V chronic kidney disease (CKD currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access. Using a factorial-design trial, patients will be randomised to aspirin or matching placebo, and also to omega-3 fatty acids or matching placebo, resulting in four treatment groups (aspirin placebo/omega-3 fatty acid placebo, aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid, aspirin/omega-3 fatty acid. Randomisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF. The medication will be commenced pre-operatively and continued for 3 months post surgery. The primary outcome is patency of the AVF at three months after randomisation. Secondary outcome measures will include functional patency at six and twelve months, primary patency time, secondary (assisted patency time, and adverse events, particularly bleeding. Discussion This multicentre Australian and New Zealand study has been designed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and/or omega-3 fatty

  18. Plasmacytoid dendritic cells in antiviral immunity and autoimmunity

    2010-01-01

    Plasmacytoid dendritic cells (pDCs) represent a unique and crucial immune cell population capable of producing large amounts of type I interferons (IFNs) in response to viral infection.The function of pDCs as the professional type I IFN-producing cells is linked to their selective expression of Toll-like receptor 7 (TLR7) and TLR9,which sense viral nucleic acids within the endosomal compartments.Type I IFNs produced by pDCs not only directly inhibit viral replication but also play an essential role in linking the innate and adaptive immune system.The aberrant activation of pDCs by self nucleic acids through TLR signaling and the ongoing production of type I IFNs do occur in some autoimmune diseases.Therefore,pDC may serve as an attractive target for therapeutic manipulations of the immune system to treat viral infectious diseases and autoimmune diseases.

  19. Formation of dendritic metallic nanowires

    Ranjan, Nitesh; Mertig, Michael [Institute for Materials Science, Max Bergmann Center of Biomaterials, Dresden University of Technology, D-01062 Dresden (Germany); Vinzelberg, Hartmut [IFW Dresden, P.O. Box 270116, D-01171 Dresden (Germany)

    2009-07-01

    Recently, we reported an electrical-field-controlled growth process for the directed bottom-up assembly of one-dimensional palladium nanowires between micro-fabricated electrodes. The wires, grown from an aqueous palladium salt solution by dielectrophoresis, had a thickness of only 5-10 nm and a length of up to several micrometers. The growth process was found to depend largely on the deposition conditions like the strength and the frequency of the applied AC field and the concentration of the metal salt solution. Here, we report the formation of thin, but straight and dendritic metallic nanowires, obtained in the low-frequency regime. The morphology of the wires was characterized by scanning force microscopy (SFM), scanning electron microscopy and transmission electron microscopy. SFM investigations revealed that the palladium nanowires grown over the glass and silicon substrates have a typical thickness of about 25 nm. Room temperature I-V measurements show them to be Ohmic in nature with a resistance of about 80 kOhm. Low-temperature measurements show the phenomenon of zero bias anomaly. The investigated growth method is capable of controllable in-place formation of complex circuit patterns for future nanoelectronics.

  20. IL-18基因修饰的成熟树突状细胞疫苗对哮喘小鼠气道炎症的预防作用%Preventive effect of IL-18 gene modified mature dendritic cells vaccine on airway inflammation in mouse asthma model

    苑航; 刘建华; 王成; 李和全; 王华英; 郑云; 夏大静

    2011-01-01

    Objective: To investigate the preventive effect of interleukin-18 (IL-18) gene modified mature dendritic cells (mDC) vaccine on airway inflammation in mouse asthma model. Methods: The asthma model was induced by injection of ovalbumin (OVA) in BALB/c mice. IL-18 gene modified mouse mature dentritic cells (mDC) were detected by flow cytometry and its capacity of inducing allogeneic T cell responses was examined by mixed lymphocyte reaction (MLR). The OVA-induced asthmatic mice were randomly divided into 6 groups: PBS group, DXM group, mDC group, Ad-LacZ -mDC group, Ad-IL-18-mDC group and control group. The pathological changes in lung tissues were assayed by HE and AB-PAS staining. The numbers of inflammatory cells and percentage of eosinophils (EOS) in bronchoalveolar lavage fluid (BALF) were counted. The levels of IFN-γ, IL-4 and IL-13 in culture supernatant of splenocytes were measured by ELISA method. The percentage of CD4 + CD25 +Foxp3 + Treg was assessed by flow cytometry analysis. Results: The vaccine was effective in decreasing the infiltration of EOS and accumulation of airway goblet cells in lung tissues, the numbers of inflammatory cells and percentage of EOS in BALF, and the levels of IL-4 and IL-13 in culture supernatant of splenocytes, and in increasing the levels of IFN-γin culture supernatant of splenocytes and the percentage of CD4+ CD25+ foxP3+ reg. Conclusion: IL-18 gene modified mDC vaccine has a preventive effect on airway inflammation in OVA-induced asthmatic mice.%目的:观察IL-18基因修饰的成熟树突状细胞(mature dendritic cells,mDC)疫苗对卵白蛋白(OVA)诱导哮喘小鼠气道炎症的预防作用.方法:采用流式细胞术分析IL-18基因修饰的成熟树突状细胞表型变化,通过混合淋巴细胞反应(MLR)检测其诱导同种异体T细胞的应答能力.BALB/c小鼠随机分成6组:健康对照组(Control组)、PBS组、地塞米松治疗组(DXM组)、成熟树突状细胞治疗组(mDC组)、LacZ基因修饰

  1. Secondary prevention of heart disease – knowledge among cardiologists and Ω-3 (Omega-3 fatty acid prescribing behaviors in Karachi, Pakistan

    Ravasia Wasik F

    2009-01-01

    Full Text Available Abstract Background The use of omega-3 fatty acids is a currently proven strategy for secondary prevention of heart disease. The prescription practices for this important nutraceutical is not currently known. It is imperative to assess the knowledge of cardiologists regarding the benefits of omega-3 fatty acids and to determine the frequency of its prescription. The aim of the study was to determine the practices and associations of dietary fish prescribing among cardiologists of Karachi and to assess their knowledge of fish oil supplementation and attitudes toward dietary practices. Methods A cross sectional survey was conducted during the period of January to March, 2008. A self report questionnaire was employed. All practicing cardiologists of Karachi were included in the study. Multiple logistic regression analysis was performed to determine the independent factors associated with high fish prescribers. Results The sample comprised of a total of 163 cardiologists practicing in Karachi, Pakistan. Most (73.6% of the cardiologists fell in the age range of 28 – 45 years and were male (90.8%. High fish prescribers only comprised 36.2% of the respondents. After adjusting for age and gender, multivariate analysis revealed that only the variable of knowledge about fish oil's role in reducing sudden cardiac death was independently associated with high fish prescribers OR = 6.38 [95% CI 2.58–15.78]. Conclusion The level of knowledge about the benefits of omega-3 fatty acids is high and the cardiologists harbor a favorable attitude towards dispensing dietary fish advice. However, the prescription practices are less than optimal and not concordant with recommendations of organisations such as the American Heart Association and National Heart Foundation of Australia. The knowledge of prevention of sudden cardiac death in CVD patients has been identified as an important predictor of high fish prescription. This particular life-saving property of omega

  2. Pollution prevention for process engineers

    Richardson, P.E.; Scheiner, B.J.; Lanzetta, F. Jr. [eds.

    1996-12-31

    Topics covered at the conference include: concepts and policies of pollution prevention; acid mine drainage; water treatment; pollution prevention - energy minerals; precious metal processing; applications of biotechnologies; emerging technologies for pollution prevention; and fertilizer industry.

  3. Dietary α-linolenic acid-rich flaxseed oil prevents against alcoholic hepatic steatosis via ameliorating lipid homeostasis at adipose tissue-liver axis in mice

    Wang, Meng; Zhang, Xiao-Jing; Feng, Kun; He, Chengwei; Li, Peng; Hu, Yuan-Jia; Su, Huanxing; Wan, Jian-Bo

    2016-01-01

    Low levels of n-3 polyunsaturated fatty acids (PUFAs) in serum and liver tissue biopsies are the common characteristics in patients with alcoholic liver disease. The α-linolenic acid (ALA) is a plant-derived n-3 PUFA and is rich in flaxseed oil. However, the impact of ALA on alcoholic fatty liver is largely unknown. In this study, we assessed the potential protective effects of ALA-rich flaxseed oil (FO) on ethanol-induced hepatic steatosis and observed that dietary FO supplementation effectively attenuated the ethanol-induced hepatic lipid accumulation in mice. Ethanol exposure stimulated adipose lipolysis but reduced fatty acid/lipid uptake, which were normalized by FO. Our investigations into the corresponding mechanisms demonstrated that the ameliorating effect of FO might be associated with the lower endoplasmic reticulum stress and normalized lipid metabolism in adipose tissue. In the liver, alcohol exposure stimulated hepatic fatty acid uptake and triglyceride synthesis, which were attenuated by FO. Additionally, dietary FO upregulated plasma adiponectin concentration, hepatic adiponectin receptor 2 expression, and the activation of hepatic adenosine monophosphate-activated protein kinase. Collectively, dietary FO protects against alcoholic hepatic steatosis by improving lipid homeostasis at the adipose tissue-liver axis, suggesting that dietary ALA-rich flaxseed oil might be a promising approach for prevention of alcoholic fatty liver. PMID:27220557

  4. Use of Tranexamic acid is a cost effective method in preventing blood loss during and after total knee replacement

    Umer Chaudhry Muhammad

    2011-05-01

    Full Text Available Abstract Background & Purpose Allogenic blood transfusion in elective orthopaedic surgery is best avoided owing to its associated risks. Total knee replacement often requires blood transfusion, more so when bilateral surgery is performed. Many strategies are currently being employed to reduce the amount of peri-operative allogenic transfusions. Anti-fibrinolytic compounds such as aminocaproic acid and tranexamic acid have been used systemically in perioperative settings with promising results. This study aimed to evaluate the effectiveness of tranexamic acid in reducing allogenic blood transfusion in total knee replacement surgery. Methodology This was a retrospective cohort study conducted on patients undergoing total knee replacement during the time period November 2005 to November 2008. Study population was 99 patients, of which 70 underwent unilateral and 29 bilateral knee replacement. Forty-seven patients with 62 (49.5% knees (group-I had received tranexamic acid (by surgeon preference while the remaining fifty-two patients with 66 (51.5% knees (group-II had did not received any tranexamic acid either pre- or post-operatively. Results The mean drop in the post-operative haemoglobin concentration in Group-II for unilateral and bilateral cases was 1.79 gm/dl and 2.21 gm/dl, with a mean post-operative drainage of 1828 ml (unilateral and 2695 ml (bilateral. In comparison, the mean drop in the post-op haemoglobin in Group-I was 1.49 gm/dl (unilateral and 1.94 gm/dl (bilateral, with a mean drainage of 826 ml (unilateral and 1288 ml (bilateral (p-value Interpretation Tranexamic acid is effective in reducing post-operative drainage and requirement of blood transfusion after knee replacement.

  5. Interfaces between dendritic cells, other immune cells, and nerve fibres in mouse Peyer's patches: potential sites for neuroinvasion in prion diseases.

    Defaweux, Valérie; Dorban, Gauthier; Demonceau, Caroline; Piret, Joëlle; Jolois, Olivier; Thellin, Olivier; Thielen, Caroline; Heinen, Ernst; Antoine, Nadine

    2005-01-01

    In this study, we examined where immune cells and nerve fibres are located in mouse Peyer's patches, with a view to identifying potential sites for neuroinvasion by prions. Special attention was paid to dendritic cells, viewed as candidate transporters of infectious prion. Double immunofluorescence labellings with anti-CD11c antibody and marker for other immune cells (B cells, T cells, follicular dendritic cells) were carried out and analysed by confocal microscopy on Peyer's patch cryosections. To reveal the extensive ganglionated networks of the myenteric and submucosal plexi and the sparse meshworks of nerve strands, we used antibodies directed against different neurofilament subunits or against glial fibrillary acidic protein. In the suprafollicular dome, dendritic cells connect, via their cytoplasmic extensions, enterocytes with M cells of the follicle-associated epithelium. They are also close to B and T cells. Nerve fibres are detected in the suprafollicular dome, notably in contact with dendritic cells. Similar connections between dendritic cells, T cells, and nerve fibres are seen in the interfollicular region. Germinal centres are not innervated; inside them dendritic cells establish contacts with follicular dendritic cells and with B cells. After immunolabelling of normal prion protein, dendritic cells of the suprafollicular dome are intensely positive labelled. PMID:15816033

  6. 中国酸雨概况及防治对策探讨%Discuss on Present Situation and Countermeasures for Acid Rain Prevention and Control in China

    刘萍; 夏菲; 潘家永; 陈益平; 彭花明; 陈少华

    2011-01-01

    中国受酸雨影响的地区已占国土面积的30%,已成为继欧州和北美之后世界第三大酸雨区。中国的酸雨为典型的硫酸型,其空间分布主要呈现以南方酸雨比北方严重,城市酸雨比郊区严重的特点。酸雨令中国农林业、畜牧业、水产养殖业、建筑业等都遭受了巨大的损失,如不采取果断有效的控制措施,由此所造成的大气污染及环境酸化将进一步加剧。本文系统阐述了中国酸雨的成因特点、现状及其危害,并根据中国酸雨的实际情况,结合国家制定的控制目标,提出了具体的防治对策。%The problem of acid rain has become an important environmental problem at present. The areas which have been affected by acid rain in our country have reached 30% of the total land area, making China the world's third largest acid rain areas nest to Europe and North America. The acid rain of China has the characteristics, including typical sulfuric acid type, more serious in south than in north in spatial distribution, more serious in cities than in suburban areas. Acid rain has inflicted great losses on agriculture, forestry, animal husbandry, aquaculture and construction. Without decisive and effective controlling measures, air pollution and environment acidification which made by acid rain will be further intensified, furthermore, it will bring greater threat to Chinese environment which is already in heavy burden. This paper describes the characteristics, situation and harms of acid rain. According to the actual situation of acid rain in China and combined with the control targets set by government, specific prevention and control countermeasures were proposed.

  7. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

    Lam Angeline

    2004-09-01

    Full Text Available Abstract Background Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD. In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. Methods This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I Determination of rates of NTDs; II Dietary assessment; III Blood analysis; IV Assessment of knowledge and use of folic acid supplements. Results The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34. The rates of NTDs fell by 78% (95% CI 65%–86% after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35. The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B12 deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. Conclusions Based on these findings, mandatory food fortification in Canada should continue at the

  8. Transformation of Leaf-like Zinc Dendrite in Oxidation and Reduction Cycle

    Highlights: • Leaf-like zinc dendrites change to leaf-like residual oxides at high oxidation current density (10 mA cm−2) whereas it completely dissolves at low oxidation current density (1 mA cm−2). • Leaf-like residual oxide products is transformed to zinc deposits with particulate morphology, resulting in good rechargeability. • The residual zinc oxide provides sufficient zincate on its reduction, preventing the diffusion-limited condition that causes leaf-like dendrite formation. - Abstract: Zinc is a promising negative electrode material for aqueous battery systems whereas it shows insufficient rechargeability for use in secondary batteries. It has been reported that leaf-like dendrite deposits are often the origin of cell-failure, however, their nature and behavior on discharge (oxidation) - charge (reduction) cycling have been only poorly understood. Here we investigate the transformation of the leaf-like zinc dendrites using ex-situ scanning electron microscopy, X-ray computational tomography and in-situ X-ray diffraction. It is shown that the leaf-like zinc dendrites obtained under diffusion-limited conditions are nearly completely dissolved at a low oxidation current density of 1 mA cm−2 and cause re-evolution of the zinc dendrites. Oxidation at a high current density of 10 mA cm−2 leads to the formation of leaf-like zinc oxide residual products that result in particulate zinc deposits in the following reduction process, enabling good rechargeability. The reaction behavior of this oxide residue is detailed and discussed for the development of long-life zinc electrodes

  9. Hyaluronic Acid Gel Injection to Prevent Thermal Injury of Adjacent Gastrointestinal Tract during Percutaneous Liver Radiofrequency Ablation

    Hasegawa, Takaaki, E-mail: hasegawat@clin.medic.mie-u.ac.jp; Takaki, Haruyuki; Miyagi, Hideki; Nakatsuka, Atsuhiro; Uraki, Junji; Yamanaka, Takashi; Fujimori, Masashi; Sakuma, Hajime; Yamakado, Koichiro [Mie University School of Medicine, Department of Radiology (Japan)

    2013-08-01

    This study evaluated the safety, feasibility, and clinical utility of hyaluronic acid gel injection to separate the gastrointestinal tract from the tumor during liver radiofrequency ablation (RFA). Eleven patients with liver tumors measuring 0.9-3.5 cm (mean {+-} standard deviation, 2.1 {+-} 0.8 cm) that were adjacent to the gastrointestinal tracts received RFA after the mixture of hyaluronic acid gel and contrast material (volume, 26.4 {+-} 14.5 mL; range, 10-60 mL) was injected between the tumor and the gastrointestinal tract under computed tomographic-fluoroscopic guidance. Each tumor was separated from the gastrointestinal tract by 1.0-1.5 cm (distance, 1.2 {+-} 0.2 cm) after injection of hyaluronic acid gel, and subsequent RFA was performed without any complications in all patients. Although tumor enhancement disappeared in all patients, local tumor progression was found in a patient (9.1 %, 1 of 11) during the follow-up of 5.5 {+-} 3.2 months (range, 0.4-9.9 months). In conclusion, hyaluronic acid gel injection is a safe and useful technique to avoid thermal injury of the adjacent gastrointestinal tract during liver RFA.

  10. Vascular composition data supporting the role of N-3 polyunsaturated fatty acids in the prevention of cardiovascular disease events.

    Ohwada, Takayuki; Yokokawa, Tetsuro; Kanno, Yuki; Hotsuki, Yu; Sakamoto, Takayuki; Watanabe, Kenichi; Nakazato, Kazuhiko; Takeishi, Yasuchika

    2016-06-01

    N-3 polyunsaturated fatty acids (PUFAs) are thought to have protective effects against cardiovascular disease. Here, we report the relationship between serum PUFA concentrations and plaque composition, as evaluated by virtual histology-intravascular ultrasound (VH-IVUS). Consecutive patients (n=61) who underwent percutaneous coronary intervention (PCI) were pre-operatively examined using VH-IVUS to assess the composition of culprit plaques. Gray-scale IVUS and VH-IVUS data of fibrous, fibro-fatty, necrotic core, and dense calcium regions of plaques were estimated at the minimal luminal area sites of culprit lesions. Serum levels of high-sensitivity C-reactive protein (hsCRP) and PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA), were compared between patients with (ACS, n=27) and without acute coronary syndrome (non-ACS, n=34) before PCI. Multiple logistic regression analysis of the data showed that EPA/AA under the median was more highly associated with ACS than hsCRP over the median. In addition, EPA/AA was negatively correlated with the percentage of fibrous plaque regions and EPA/AA and DHA/AA were positively correlated with the percentage of dense calcium regions in plaques. Furthermore, the correlation index of EPA/AA was the most highly (R=0.513) correlated with the percentage of dense calcium regions in plaques. PMID:27222841

  11. Hyaluronic Acid Gel Injection to Prevent Thermal Injury of Adjacent Gastrointestinal Tract during Percutaneous Liver Radiofrequency Ablation

    This study evaluated the safety, feasibility, and clinical utility of hyaluronic acid gel injection to separate the gastrointestinal tract from the tumor during liver radiofrequency ablation (RFA). Eleven patients with liver tumors measuring 0.9–3.5 cm (mean ± standard deviation, 2.1 ± 0.8 cm) that were adjacent to the gastrointestinal tracts received RFA after the mixture of hyaluronic acid gel and contrast material (volume, 26.4 ± 14.5 mL; range, 10–60 mL) was injected between the tumor and the gastrointestinal tract under computed tomographic–fluoroscopic guidance. Each tumor was separated from the gastrointestinal tract by 1.0–1.5 cm (distance, 1.2 ± 0.2 cm) after injection of hyaluronic acid gel, and subsequent RFA was performed without any complications in all patients. Although tumor enhancement disappeared in all patients, local tumor progression was found in a patient (9.1 %, 1 of 11) during the follow-up of 5.5 ± 3.2 months (range, 0.4–9.9 months). In conclusion, hyaluronic acid gel injection is a safe and useful technique to avoid thermal injury of the adjacent gastrointestinal tract during liver RFA

  12. Identification of genetic loci in Lactobacillus plantarum that modulate the immune response of dendritic cells using comparative genome hybridization.

    Marjolein Meijerink

    Full Text Available BACKGROUND: Probiotics can be used to stimulate or regulate epithelial and immune cells of the intestinal mucosa and generate beneficial mucosal immunomodulatory effects. Beneficial effects of specific strains of probiotics have been established in the treatment and prevention of various intestinal disorders, including allergic diseases and diarrhea. However, the precise molecular mechanisms and the strain-dependent factors involved are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we aimed to identify gene loci in the model probiotic organism Lactobacillus plantarum WCFS1 that modulate the immune response of host dendritic cells. The amounts of IL-10 and IL-12 secreted by dendritic cells (DCs after stimulation with 42 individual L. plantarum strains were measured and correlated with the strain-specific genomic composition using comparative genome hybridisation and the Random Forest algorithm. This in silico "gene-trait matching" approach led to the identification of eight candidate genes in the L. plantarum genome that might modulate the DC cytokine response to L. plantarum. Six of these genes were involved in bacteriocin production or secretion, one encoded a bile salt hydrolase and one encoded a transcription regulator of which the exact function is unknown. Subsequently, gene deletions mutants were constructed in L. plantarum WCFS1 and compared to the wild-type strain in DC stimulation assays. All three bacteriocin mutants as well as the transcription regulator (lp_2991 had the predicted effect on cytokine production confirming their immunomodulatory effect on the DC response to L. plantarum. Transcriptome analysis and qPCR data showed that transcript level of gtcA3, which is predicted to be involved in glycosylation of cell wall teichoic acids, was substantially increased in the lp_2991 deletion mutant (44 and 29 fold respectively. CONCLUSION: Comparative genome hybridization led to the identification of gene loci in L

  13. Mitoprotective antioxidant EUK-134 stimulates fatty acid oxidation and prevents hypertrophy in H9C2 cells.

    Purushothaman, Sreeja; Nair, R Renuka

    2016-09-01

    Oxidative stress is an important contributory factor for the development of cardiovascular diseases like hypertension-induced hypertrophy. Mitochondrion is the major source of reactive oxygen species. Hence, protecting mitochondria from oxidative damage can be an effective therapeutic strategy for the prevention of hypertensive heart disease. Conventional antioxidants are not likely to be cardioprotective, as they cannot protect mitochondria from oxidative damage. EUK-134 is a salen-manganese complex with superoxide dismutase and catalase activity. The possible role of EUK-134, a mitoprotective antioxidant, in the prevention of hypertrophy of H9C2 cells was examined. The cells were stimulated with phenylephrine (50 μM), and hypertrophy was assessed based on cell volume and expression of brain natriuretic peptide and calcineurin. Enhanced myocardial lipid peroxidation and protein carbonyl content, accompanied by nuclear factor-kappa B gene expression, confirmed the presence of oxidative stress in hypertrophic cells. Metabolic shift was evident from reduction in the expression of medium-chain acyl-CoA dehydrogenase. Mitochondrial oxidative stress was confirmed by the reduced expression of mitochondria-specific antioxidant peroxiredoxin-3 and enhanced mitochondrial superoxide production. Compromised mitochondrial function was apparent from reduced mitochondrial membrane potential. Pretreatment with EUK-134 (10 μM) was effective in the prevention of hypertrophic changes in H9C2 cells, reduction of oxidative stress, and prevention of metabolic shift. EUK-134 treatment improved the oxidative status of mitochondria and reversed hypertrophy-induced reduction of mitochondrial membrane potential. Supplementation with EUK-134 is therefore identified as a novel approach to attenuate cardiac hypertrophy and lends scope for the development of EUK-134 as a therapeutic agent in the management of human cardiovascular disease. PMID:27514538

  14. Ursolic acid protects monocytes against metabolic stress-induced priming and dysfunction by preventing the induction of Nox4

    Sarah L. Ullevig

    2014-01-01

    Conclusion: UA protects THP-1 monocytes against dysfunction by suppressing metabolic stress-induced Nox4 expression, thereby preventing the Nox4-dependent dysregulation of redox-sensitive processes, including actin turnover and MAPK-signaling, two key processes that control monocyte migration and adhesion. This study provides a novel mechanism for the anti-inflammatory and athero- and renoprotective properties of UA and suggests that dysfunctional blood monocytes may be primary targets of UA and related compounds.

  15. Dendrites Inhibition in Rechargeable Lithium Metal Batteries

    Aryanfar, Asghar

    The specific high energy and power capacities of rechargeable lithium metal (Li0) batteries are ideally suited to portable devices and are valuable as storage units for intermittent renewable energy sources. Lithium, the lightest and most electropositive metal, would be the optimal anode material for rechargeable batteries if it were not for the fact that such devices fail unexpectedly by short-circuiting via the dendrites that grow across electrodes upon recharging. This phenomenon poses a major safety issue because it triggers a series of adverse events that start with overheating, potentially followed by the thermal decomposition and ultimately the ignition of the organic solvents used in such devices. In this thesis, we developed experimental platform for monitoring and quantifying the dendrite populations grown in a Li battery prototype upon charging under various conditions. We explored the effects of pulse charging in the kHz range and temperature on dendrite growth, and also on loss capacity into detached "dead" lithium particles. Simultaneously, we developed a computational framework for understanding the dynamics of dendrite propagation. The coarse-grained Monte Carlo model assisted us in the interpretation of pulsing experiments, whereas MD calculations provided insights into the mechanism of dendrites thermal relaxation. We also developed a computational framework for measuring the dead lithium crystals from the experimental images.

  16. Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.

    Michael J Schachter

    Full Text Available The On-Off direction-selective ganglion cell (DSGC in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within

  17. Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.

    Schachter, Michael J; Oesch, Nicholas; Smith, Robert G; Taylor, W Rowland

    2010-01-01

    The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials) are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within cortical circuitry

  18. Preeclampsia prevention

    Vitorino Modesto Santos

    2016-04-01

    Full Text Available Colombia and Brazil are developing countries where pregnancy-related hypertensive disorders and associated conditions constitute major concerns in public health area. Calcium plus conjugated linoleic acid used by pregnant adolescents had preventive effect on PE, but the prevention did not occur with utilization of calcium alone. After implementation of Colombian prenatal care program based on the bio-psychosocial model, maternal mortality and the rate of PE reduced in 23% and 22%, respectively. Late postpartum eclampsia, is the onset of seizuress more than 48 hours, but less than four weeks after delivery. This severe condition may occur without antecedent of PE. Lower maternal mortality due to preeclampsia/ eclampsia can follow implementation of prenatal programs based on BPSM, and use of calcium plus conjugated linoleic acid

  19. Conjugated linoleic acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis

    Rahman, Md Mizanur; Fernandes, Gabriel; Williams, Paul

    2013-01-01

    Postmenopausal osteoporosis due to estrogen deficiency is associated with severe morbidity and mortality. Beneficial effects of conjugated linoleic acid (CLA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the effect of long term CLA supplementation against ovariectomy-induced bone loss in mice and the mechanisms underlying this effect have not been studied yet. Eight weeks old ovariectomized (Ovx) and sham operated C57BL/6 mice were fed either a diet containin...

  20. Protocatechuic Acid Prevents oxLDL-Induced Apoptosis by Activating JNK/Nrf2 Survival Signals in Macrophages

    Rosaria Varì; Beatrice Scazzocchio; Carmela Santangelo; Carmelina Filesi; Fabio Galvano; Massimo D’Archivio; Roberta Masella; Claudio Giovannini

    2015-01-01

    Protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, exerts numerous biological activities including antiapoptotic, anti-inflammatory, and antiatherosclerotic effects. Oxidised LDL have atherogenic properties by damaging arterial wall cells and inducing p53-dependent apoptosis in macrophages. This study was aimed at defining the molecular mechanism responsible for the protective effects of PCA against oxidative and proapoptotic damage exerted by oxLDL in J774 A.1 mac...

  1. The prevention of peritoneal adhesions by in-situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives

    Ito, Taichi; Yeo, Yoon; Highley, Christopher B.; Bellas, Evangelia; Benitez, Carlos A; Kohane, Daniel S.

    2006-01-01

    Postoperative peritoneal adhesions can cause pelvic pain, infertility, and potentially lethal bowel obstruction. We have designed and synthesized injectable hydrogels that are formed by mixing hydrazide-modified hyaluronic acid (HA) with aldehyde-modified versions of cellulose derivatives such as carboxymethylcellulose (CMC), hydroxypropylmethyl cellulose (HPMC), and methyl cellulose (MC). Gelation of these hydrogels occurred in less than 1 min, and had higher shear moduli than that of HA-HA ...

  2. A novel approach to the protection of cocoa beans by preventing free fatty acid formation under hermetic storage

    Navarro, S; Navarro, H. (Hipólito); Finkelman, S.; Jonfia-Essien, W. A.

    2010-01-01

    Hermetic storage has provided a successful storage method for the protection of dry cocoa beans by replacing fumigants for insect control and for quality preservation. Hermetic storage is achieved in specially constructed flexible plastic structures and is based on the principle of generation of an oxygendepleted, carbon dioxide-enriched interstitial atmosphere caused by the respiration of the living organisms in the ecological system of a sealed storage. An increase in free fatty acids (FFA...

  3. Medium-chain fatty acids and plant-derived antimicrobials to prevent Campylobacter colonization in broiler chickens

    Hermans, David; Haesebrouck, Freddy; Van Deun, Kim; Martel, An; Verlinden, Marc; Garmyn, An; Heyndrickx, Marc; Pasmans, Frank

    2011-01-01

    Campylobacter jejuni is the most common cause of bacterial-mediated diarrhoeal disease worldwide. Because poultry products are a major source of C. jejuni infections in humans, efforts should be taken to develop strategies to decrease Campylobacter colonization of poultry during primary production. Organic acids and plant-derived antimicrobial compounds possess marked bactericidal activity toward C. jejuni in vitro and might therefore have potential as feed additives to control C. jejuni colo...

  4. Corrosion Behavior of Ti-Based In Situ Dendrite-Reinforced Metallic Glass Matrix Composites in Various Solutions

    Yang, F.; Tian, H. F.; Lan, A. D.; Zhou, H. F.; Wang, B. C.; Yang, H. J.; Qiao, J. W.

    2015-06-01

    The electrochemical corrosion behaviors of Ti40Zr24V12Cu5Be19 in situ dendrite-reinforced metallic glass matrix composites (MGMCs) were investigated by potentiodynamic polarization experiments and electrochemical impedance spectroscopy in acidic, salty, and alkaline solutions. Ti40Zr24V12Cu5Be19 in situ dendrite-reinforced MGMCs have an impressive corrosion resistance in strong acidic environment, while their performance was not so great in strong alkaline environment. Further immersion test in same solutions revealed similar chemical corrosion behaviors. XRD and SEM examinations were conducted to check the structure and surface modification of the material during the corrosion process. EDS test indicated that the amorphous matrices, which show excellent corrosion resistance, have a considerable composition variation from its crystalline dendrites counterpart.

  5. Detecting Danger: The Dendritic Cell Algorithm

    Greensmith, Julie; Cayzer, Steve

    2010-01-01

    The Dendritic Cell Algorithm (DCA) is inspired by the function of the dendritic cells of the human immune system. In nature, dendritic cells are the intrusion detection agents of the human body, policing the tissue and organs for potential invaders in the form of pathogens. In this research, and abstract model of DC behaviour is developed and subsequently used to form an algorithm, the DCA. The abstraction process was facilitated through close collaboration with laboratory- based immunologists, who performed bespoke experiments, the results of which are used as an integral part of this algorithm. The DCA is a population based algorithm, with each agent in the system represented as an 'artificial DC'. Each DC has the ability to combine multiple data streams and can add context to data suspected as anomalous. In this chapter the abstraction process and details of the resultant algorithm are given. The algorithm is applied to numerous intrusion detection problems in computer security including the detection of p...

  6. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region.

    Wang, Haochen; De Steur, Hans; Chen, Gong; Zhang, Xiaotian; Pei, Lijun; Gellynck, Xavier; Zheng, Xiaoying

    2016-01-01

    Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207-0473, p Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China. PMID:27005659

  7. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region

    Haochen Wang

    2016-03-01

    Full Text Available Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages and a control group received ordinary flour (three villages. NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207–0473, p < 0.001. In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory folic acid fortification in China.

  8. Self-antigen presentation by dendritic cells and lymphoid stroma and its implications for autoimmunity

    Lukacs-Kornek, Veronika; Turley, Shannon J.

    2010-01-01

    The induction and maintenance of T cell tolerance is essential to prevent autoimmunity. A combination of central and peripheral mechanisms acts to control autoreactive T cells. In secondary lymphoid organs, dendritic cells (DCs) presenting self-antigen were thought to play a major role in the induction of peripheral T cell tolerance. Multiple recent studies have demonstrated that DCs are not absolutely essential to induce and maintain tolerance. Furthermore, it has also been recently shown th...

  9. Preventing stroke

    Stroke - prevention; CVA - prevention; cerebral vascular accident - prevention; TIA - prevention, transient ischemic attack - prevention ... live a longer, healthier life. This is called preventive care. An important way to help prevent stroke ...

  10. The Dendritic Hypothesis for Alzheimer’s Disease Pathophysiology

    Cochran, J. Nicholas; Hall, Alicia M.; Roberson, Erik D.

    2013-01-01

    Converging evidence indicates that processes occurring in and around neuronal dendrites are central to the pathogenesis of Alzheimer’s disease. These data support the concept of a “dendritic hypothesis” of AD, closely related to the existing synaptic hypothesis. Here we detail dendritic neuropathology in the disease and examine how Aβ, tau, and AD genetic risk factors affect dendritic structure and function. Finally, we consider potential mechanisms by which these key drivers could affect den...

  11. Oxidation of calprotectin by hypochlorous acid prevents chelation of essential metal ions and allows bacterial growth: Relevance to infections in cystic fibrosis.

    Magon, Nicholas J; Turner, Rufus; Gearry, Richard B; Hampton, Mark B; Sly, Peter D; Kettle, Anthony J

    2015-09-01

    Calprotectin provides nutritional immunity by sequestering manganese and zinc ions. It is abundant in the lungs of patients with cystic fibrosis but fails to prevent their recurrent infections. Calprotectin is a major protein of neutrophils and composed of two monomers, S100A8 and S100A9. We show that the ability of calprotectin to limit growth of Staphylococcus aureus and Pseudomonas aeruginosa is exquisitely sensitive to oxidation by hypochlorous acid. The N-terminal cysteine residue on S100A9 was highly susceptible to oxidation which resulted in cross-linking of the protein monomers. The N-terminal methionine of S100A8 was also readily oxidized by hypochlorous acid, forming both the methionine sulfoxide and the unique product dehydromethionine. Isolated human neutrophils formed these modifications on calprotectin when their myeloperoxidase generated hypochlorous acid. Up to 90% of the N-terminal amine on S100A8 in bronchoalveolar lavage fluid from young children with cystic fibrosis was oxidized. Oxidized calprotectin was higher in children with cystic fibrosis compared to disease controls, and further elevated in those patients with infections. Our data suggest that oxidative stress associated with inflammation in cystic fibrosis will stop metal sequestration by calprotectin. Consequently, strategies aimed at blocking extracellular myeloperoxidase activity should enable calprotectin to provide nutritional immunity within the airways. PMID:26006104

  12. Study on Formation,Haz-ards, Prevention and Control of Acid Rain%酸雨的形成、危害和防控研究

    祝晓红

    2014-01-01

    Acid rain refers to the me-teoric water which the pH value is lower than 5.60, and it’s serious environmental pollution phenomenon, which affects hu-man life and property security, the pro-tection of ecological environment and e-conomic and social development.The harm of acid rain is growing, mainly due to the increase of sulfide , nitrogen ox-ides and other toxic gases of the air. To reduce the hazards of acid rain,there must be take steps to prevent and control of pollution emissions from the source, and strengthen the development and uti-lization of new energy.%酸雨是指pH小于5.60的大气降水,是一种严重的环境污染现象,其直接影响着人类生命财产安全、生态环境保护、经济社会发展等。大气酸雨问题日益严重,造成酸雨的主要原因是大气中二氧化硫、氮氧化物等有毒气体含量的增加。要减少酸雨的危害,必须从污染源的排放进行防控,同时加强对新能源的开发和利用。

  13. Formate supplementation enhances folate-dependent nucleotide biosynthesis and prevents spina bifida in a mouse model of folic acid-resistant neural tube defects.

    Sudiwala, Sonia; De Castro, Sandra C P; Leung, Kit-Yi; Brosnan, John T; Brosnan, Margaret E; Mills, Kevin; Copp, Andrew J; Greene, Nicholas D E

    2016-07-01

    The curly tail mouse provides a model for neural tube defects (spina bifida and exencephaly) that are resistant to prevention by folic acid. The major ct gene, responsible for spina bifida, corresponds to a hypomorphic allele of grainyhead-like 3 (Grhl3) but the frequency of NTDs is strongly influenced by modifiers in the genetic background. Moreover, exencephaly in the curly tail strain is not prevented by reinstatement of Grhl3 expression. In the current study we found that expression of Mthfd1L, encoding a key component of mitochondrial folate one-carbon metabolism (FOCM), is significantly reduced in ct/ct embryos compared to a partially congenic wild-type strain. This expression change is not attributable to regulation by Grhl3 or the genetic background at the Mthfd1L locus. Mitochondrial FOCM provides one-carbon units as formate for FOCM reactions in the cytosol. We found that maternal supplementation with formate prevented NTDs in curly tail embryos and also resulted in increased litter size. Analysis of the folate profile of neurulation-stage embryos showed that formate supplementation resulted in an increased proportion of formyl-THF and THF but a reduction in proportion of 5-methyl THF. In contrast, THF decreased and 5-methyl THF was relatively more abundant in the liver of supplemented dams than in controls. In embryos cultured through the period of spinal neurulation, incorporation of labelled thymidine and adenine into genomic DNA was suppressed by supplemental formate, suggesting that de novo folate-dependent biosynthesis of nucleotides (thymidylate and purines) was enhanced. We hypothesise that reduced Mthfd1L expression may contribute to susceptibility to NTDs in the curly tail strain and that formate acts as a one-carbon donor to prevent NTDs. PMID:26924399

  14. Silicon dendritic web growth thermal analysis task

    Richter, R.; Bhandari, P.

    1985-01-01

    A thermal analysis model is presented which describes the dendritic ribbon process. The model uses a melt-dendrite interface which projects out of the bulk melt as the basic interpretation of the ribbon production process. This is a marked departure from the interpretations of the interface phenomena which were used previously. The model was extensively illustrated with diagrams and pictures of ribbon samples. This model should have great impact on the analyses of experimental data as well as on future design modifications of ribbon-pulling equipment.

  15. Topical Hyaluronic Acid vs. Standard of Care for the Prevention of Radiation Dermatitis After Adjuvant Radiotherapy for Breast Cancer: Single-Blind Randomized Phase III Clinical Trial

    Pinnix, Chelsea; Perkins, George H.; Strom, Eric A.; Tereffe, Welela; Woodward, Wendy; Oh, Julia L.; Arriaga, Lisa [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Munsell, Mark F. [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Kelly, Patrick; Hoffman, Karen E.; Smith, Benjamin D.; Buchholz, Thomas A. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Yu, T. Kuan, E-mail: tkyu@houstonprecisioncc.com [Houston Precision Cancer Center, Houston, TX (United States)

    2012-07-15

    Purpose: To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of {>=}Grade 2 radiation dermatitis after adjuvant breast radiation compared with best supportive care. Methods and Materials: Women with breast cancer who had undergone lumpectomy and were to receive whole-breast radiotherapy to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel on the medial half or the lateral half of the irradiated breast and to use the control gel on the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of {>=}Grade 2 dermatitis. Results: The study closed early on the basis of a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed a significantly higher rate of {>=}Grade 2 dermatitis than did skin treated with petrolatum gel: 61.5% (40/65) vs. 47.7% (31/65) (p = 0.027). Only 1ne patient developed Grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than in that treated with petrolatum gel at the end of radiotherapy (42% vs. 14%, p = 0.003). Conclusion: We found no benefit from the use of a topical hyaluronic acid-based gel for reducing the development of {>=}Grade 2 dermatitis after adjuvant radiotherapy for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop.

  16. Apoptosis and systemic autoimmunity: the dendritic cell connection

    AA Manfredi

    2009-12-01

    Full Text Available Much effort has been devoted in recent years to the events linking recognition and disposal of apoptotic cells to sustained immunity towards the antigens they contain. Programmed death via apoptosis indeed provides most of the raw material the immune system exploits to establish self tolerance, i.e. to learn how to distinguish between self constituents and foreign antigens, belonging to invading pathogens. In parallel, events occurring during cell death may enable a restricted array of molecules endowed with diverse structure, function and intracellular distribution to satisfy the requirement to evoke and maintain autoimmune responses. Dendritic cells (DCs, the most potent antigen presenting cells, appear to play a crucial role. Here we will discuss some of the constrains regulating the access of dying cells’ antigens to DCs, as well as censorship mechanisms that prevent their maturation and the full explication of their antigen presenting function.

  17. The influence of infectious factors on dendritic cell apoptosis.

    Kubicka-Sierszen, Agata; Grzegorczyk, Janina Ł

    2015-10-12

    Pathogens can have a negative influence on dendritic cells (DCs), causing their apoptosis, which prevents active presentation of foreign antigens. It results in a state of immunosuppression which makes the body susceptible to secondary infections. Infected immature DCs have lower expression of co-stimulatory and adhesion molecules, reduced ability to secrete cytokines and an inhibited maturation process and are incapable of effective antigen presentation and activation of T-lymphocytes. In some cases, the ability of DCs to undergo rapid apoptosis is important for the body defense, which is probably because of DCs' ability to cross-present and cooperate with other cells. Apoptotic bodies released from the infected DCs are phagocytosed by other DCs, which then stimulate the effector cells and present antigens more efficiently than infected cells. The aim of this article is to review how the DCs respond to viral and bacterial factors and which biochemical mechanisms are responsible for their apoptosis. PMID:26528349

  18. Regulation of intestinal immune system by dendritic cells.

    Ko, Hyun-Jeong; Chang, Sun-Young

    2015-02-01

    Innate immune cells survey antigenic materials beneath our body surfaces and provide a front-line response to internal and external danger signals. Dendritic cells (DCs), a subset of innate immune cells, are critical sentinels that perform multiple roles in immune responses, from acting as principal modulators to priming an adaptive immune response through antigen-specific signaling. In the gut, DCs meet exogenous, non-harmful food antigens as well as vast commensal microbes under steady-state conditions. In other instances, they must combat pathogenic microbes to prevent infections. In this review, we focus on the function of intestinal DCs in maintaining intestinal immune homeostasis. Specifically, we describe how intestinal DCs affect IgA production from B cells and influence the generation of unique subsets of T cell. PMID:25713503

  19. The bHLH-PAS protein Spineless is necessary for the diversification of dendrite morphology of Drosophila dendritic arborization neurons

    Kim, Michael D.; Jan, Lily Yeh; Jan, Yuh Nung

    2006-01-01

    Dendrites exhibit a wide range of morphological diversity, and their arborization patterns are critical determinants of proper neural connectivity. How different neurons acquire their distinct dendritic branching patterns during development is not well understood. Here we report that Spineless (Ss), the Drosophila homolog of the mammalian aryl hydrocarbon (dioxin) receptor (Ahr), regulates dendrite diversity in the dendritic arborization (da) sensory neurons. In loss-of-function ss mutants, c...

  20. SFH2 regulates fatty acid synthase activity in the yeast Saccharomyces cerevisiae and is critical to prevent saturated fatty acid accumulation in response to haem and oleic acid depletion

    Desfougères, Thomas; Ferreira, Thierry; Bergès, Thierry; Régnacq, Matthieu

    2007-01-01

    Abstract The yeast Saccharomyces cerevisiae is a facultative anaerobic organism. In anaerobiosis, sustained growth relies on the presence of exogenously supplied unsaturated fatty acids and ergosterol that yeast is unable to synthesize in the absence of oxygen or upon haem depletion. In the absence of exogenous supplementation with unsaturated fatty acid, a net accumulation of saturated fatty acid (SFA) is observed that induces significant modification of phospholipid profile [1]. ...

  1. Evidence that the branched-chain amino acid L-valine prevents exercise-induced release of 5-HT in rat hippocampus.

    Gomez-Merino, D; Béquet, F; Berthelot, M; Riverain, S; Chennaoui, M; Guezennec, C Y

    2001-07-01

    The branched-chain amino acid L-valine competes with tryptophan for transport into the brain and has previously been shown to decrease brain 5-HT synthesis. The purpose of this study was to assess, using a combined venous catheterization and in vivo microdialysis method, the effect of pre-exercise L-valine administration on 5-hydroxytryptamine (5-HT) metabolism in the ventral hippocampus of rats submitted to an acute intensive treadmill running (120 min at 25 m x min(-1) followed by 150 min of recovery). The presented results include measurement of extracellular tryptophan (TRP), the 5-HT precursor, and extracellular 5-hydroxyindoleacetic acid (5-HIAA), the 5-HT metabolite. The data clearly demonstrate that exercise induces 5-HT release in the rat hippocampus: in control group, hippocampal 5-HT levels increase from 123.7 +/- 6.4% at the end of exercise to 133.9 +/- 6.4% after 60 min of recovery. Moreover, two hours of intensive running induced significant increases both in extracellular TRP levels (from 120 min of exercise to 30 min of recovery) and 5-HIAA levels (from 90 min of exercise to 90 min of recovery). Pre-exercise administration of L-valine prevents significantly the exercise-induced 5-HT release: 5-HT levels are maintained to baseline during exercise and recovery. With regard to the competitive effect of L-valine with TRP, we could observe a treatment-induced decrease in brain TRP levels (from 120 min of exercise to the end of recovery). Besides, L-valine does not prevent exercise-induced increase in 5-HIAA levels. The present study evidences that an acute intensive exercise stimulates 5-HT metabolism in the rat hippocampus, and that a pre-exercise administration of L-valine prevents, via a limiting effect on 5-HT synthesis, exercise-induced 5-HT release. This study provides some anwers to previous human and animal investigations, showing physiological and psychological benefits of branched-chain amino acids supplementation on performance. PMID:11510866

  2. SFH2 regulates fatty acid synthase activity in the yeast Saccharomyces cerevisiae and is critical to prevent saturated fatty acid accumulation in response to haem and oleic acid depletion.

    Desfougères, Thomas; Ferreira, Thierry; Bergès, Thierry; Régnacq, Matthieu

    2008-01-01

    The yeast Saccharomyces cerevisiae is a facultative anaerobic organism. Under anaerobiosis, sustained growth relies on the presence of exogenously supplied unsaturated fatty acids and ergosterol that yeast is unable to synthesize in the absence of oxygen or upon haem depletion. In the absence of exogenous supplementation with unsaturated fatty acid, a net accumulation of SFA (saturated fatty acid) is observed that induces significant modification of phospholipid profile [Ferreira, Régnacq, Alimardani, Moreau-Vauzelle and Bergès (2004) Biochem. J. 378, 899-908]. In the present paper, we focus on the role of SFH2/CSR1, a hypoxic gene related to SEC14 and its involvement in lipid metabolism upon haem depletion in the absence of oleic acid supplementation. We observed that inactivation of SFH2 results in enhanced accumulation of SFA and phospholipid metabolism alterations. It results in premature growth arrest and leads to an exacerbated sensitivity to exogenous SFA. This phenotype is suppressed in the presence of exogenous oleic acid, or by a controlled expression of FAS1, one of the two genes encoding FAS. We present several lines of evidence to suggest that Sfh2p and oleic acid regulate SFA synthase in yeast at different levels: whereas oleic acid acts on FAS2 at the transcriptional level, we show that Sfh2p inhibits fatty acid synthase activity in response to haem depletion. PMID:17803462

  3. Model of Primary Austenite Dendrite Structure in Hypoeutectic Cast Iron

    2003-01-01

    The solidification of primary austenite in hypoeutectic gray cast iron was studied by stepped grinding and quantitative metallography. The dendrite structure of primary austenite can be described by three models: typical dendrite crystal model, metamorphic dendrite crystal model and network dendrite crystal model. The dendrite crystals formed according to 3rd model is much more than those formed according to other models in this experiment. The primary austenites are connected each other, and the primary stems of austenite could be regarded as secondary arms and vice versa.

  4. Numerical Simulations of Equiaxed Dendrite Growth Using Phase Field Method

    2002-01-01

    Phase field method offers the prospect of being able to perform realistic numerical experiments on dendrite growthin a metallic system. In this paper, the equiaxed dendrite evolution during the solidification of a pure material wasnumerically simulated using the phase field model. The equiaxed dendrite growth in a two-dimensional square domainof undercooled melt (nickel) with four-fold anisotropy was simulated. The phase field model equations was solvedusing the explicit finite difference method on a uniform mesh. The formation of various equiaxed dendrite patternswas shown by a series of simulations, and the effect of anisotropy on equiaxed dendrite morphology was investigated.

  5. Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet

    Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor γ activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGFβ1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis

  6. Topical vaccination with functionalized particles targeting dendritic cells.

    Baleeiro, Renato B; Wiesmüller, Karl-Heinz; Reiter, Yoran; Baude, Barbara; Dähne, Lars; Patzelt, Alexa; Lademann, Jürgen; Barbuto, José A; Walden, Peter

    2013-08-01

    Needle-free vaccination, for reasons of safety, economy, and convenience, is a central goal in vaccine development, but it also needs to meet the immunological requirements for efficient induction of prophylactic and therapeutic immune responses. Combining the principles of noninvasive delivery to dendritic cells (DCs) through skin and the immunological principles of cell-mediated immunity, we developed microparticle-based topical vaccines. We show here that the microparticles are efficient carriers for coordinated delivery of the essential vaccine constituents to DCs for cross-presentation of the antigens and stimulation of T-cell responses. When applied to the skin, the microparticles penetrate into hair follicles and target the resident DCs, the immunologically most potent cells and site for induction of efficient immune responses. The microparticle vaccine principle can be applied to different antigen formats such as peptides and proteins, or nucleic acids coding for the antigens. PMID:23426134

  7. Dendritic cells in peripheral tolerance and immunity

    Gad, Monika; Claesson, Mogens Helweg; Pedersen, Anders Elm

    Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular...

  8. Skin Dendritic Cells in Burn Patients

    D’Arpa, N.; D’Amelio, L.; Accardo-Palumbo, A.; Pileri, D.; Mogavero, R.; Amato, G.; Napoli, B.; Alessandro, G.; Lombardo, C.; F. Conte

    2009-01-01

    The body's immunological response to burn injury has been a subject of great inquiry in recent years. Burn injury disturbs the immune system, resulting in a progressive suppression of the immune response that is thought to contribute to the development of sepsis. Dendritic cells (DCs) are potent antigen-presenting cells that possess the ability to stimulate naïve T cells.

  9. Generation of Immune Inhibitory Dendritic Cells and

    Abediankenari Saeid

    2009-03-01

    Full Text Available Variety of positive as well as negative regulatory signals are provided by antigen presenting cell in particular by dendritic cells. In this research, we studied the capacity of dendritic cells to expand antigen-specific T regulatory cells.We also investigated the role of TGF-beta in induction inhibitory functions of dendritic cells in mixed leukocyte reactions.Dendritic cells were generated from blood CD14+ monocytes with granulocyte-Monocyte colony stimulating factor and interleukin-4 with or without TGF-beta (TGF-β-GM-DC or GM-DC. CD4+ T cell were isolated to assess lymphocyte proliferation by lymphocyte transformation test assay and the ratio of CD4+FOXp3+ CD25+ T cells were determined by fluorescene-activated cell sorter. T cell proliferation responses in GM-DC showed a significance antigen-specific proliferative response comparing with TGFβ-GM -DC. T Cell proliferation was inhibited in co-culture system containing DC-treated TGF-β. It can be suggested that the expsansion of T regulatory by TGF-β-GM-DC provides a means for antigen specific control of unwanted immune reactions.

  10. Antigen dynamics of follicular dendritic cells

    Heesters, B.A.

    2015-01-01

    Stromal-derived follicular dendritic cells (FDCs) are a major depot for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate and high-affinity antibody production takes place. Historically, FDCs have been characterized as ‘accessory’

  11. ISOLATION OF CHICKEN FOLLICULAR DENDRITIC CELLS

    The aim of the present study was to isolate chicken follicular dendritic cells (FDC). A combination of methods involving panning, iodixanol density gradient centrifugation, and magnetic cell separation technology made it possible to obtain functional FDC from the cecal tonsils from chickens, which h...

  12. Glycyrrhizic acid prevents astrocyte death by neuromyelitis optica-specific IgG via inhibition of C1q binding.

    Kim, Ji-Sun; Cheon, Soyoung; Kim, Seung Woo; Kim, Boram; Kim, Heejaung; Park, Ki Duk; Kim, Sung-Min

    2016-09-16

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system and is mediated by complement-dependent cytotoxicity (CDC) of NMO-specific immunoglobulin G (IgG) antibodies (NMO-IgG). Glycyrrhizic acid (GA) has numerous pharmacological effects including inhibition of the complement pathway. We aimed to study the influence of GA on NMO-IgG-induced CDC. NMO-IgG samples from 7 patients with NMO, together with human complement, induced CDC in an aquaporin 4 M23-overexpressing glial cell line, an in vitro NMO model. GA attenuated NMO-IgG-induced CDC in a dose-dependent manner. The mechanism of the GA-related CDC inhibition was sequentially dissected and found to involve inhibition of C1q binding to NMO-IgG. Consequently, GA attenuates NMO-IgG-induced CDC and may be a promising novel therapeutic agent against NMO. PMID:27462020

  13. A single dose of caffeic acid phenethyl ester prevents initiation in a medium-term rat hepatocarcinogenesis model

    Claudia Esther Carrasco-Legleu; Yesennia Sánchez-Pérez; Lucrecia Márquez-Rosado; Samia Fattel-Fazenda; Evelia Arce-Popoca; Sergio Hernández-García; Saú1 Villa-Trevi(n)o

    2006-01-01

    AIM:To study of the effect of caffeic acid phenethyl ester (CAPE) on the initiation period in a medium-term assay of hepatocarcinogenesis.METHODS: Male Wistar rats were subjected to a carcinogenic treatment (CT) and sacrificed at 25th d;altered hepatic foci (AHF) were generated efficiently.To a second group of rats a single 20 mg/kg doses of CAPE was given 12 h before initiation with CT and were sacrificed at 25th d. We evaluated the expression of preneoplastic markers as y-glutamyltranspeptidase (GGT) and glutathione S-transferase type pi protein (GSTp) by histochemistry, RT-PCR and Western blot analyses, respectively. We measured thiobarbituric acid reactive substances (TBARS) in homogenates of liver and used Unscheduled DNA Synthesis (UDS) assay by incorporation of [3H] thymidine (3HdT) in primary hepatocyte cultures (PHC).RESULTS:At 25th d after CT CAPE reduced the observed increase of GGT+AHF by 84% and liver expression of ggt mRNA by 100%. In case of the GSTp protein, the level was reduced by 90%. As indicative of oxidative stress generated by diethylnitrosamine (DEN) 12 h after its administration, we detected a 68% increase of TBARS.When CAPE was administered before DEN, it completely protected from liver TBARS induction. To have an indication of the sole effect of CAPE on initiation, two carcinogens were tested in a UDS assay in PHC, we used methyl-n-nitrosoguanidine as a direct carcinogen and DEN, as indirect carcinogen. In this assay, genotoxic damage caused by carcinogens was abolished at 5μM CAPE concentration.CONCLUSION:Our results demonstrated that CAPE possesses anti-genotoxic and antineoplastic capabilities,by an anti-oxidative and free-radical scavenging mechanism.

  14. DEX-1 and DYF-7 establish sensory dendrite length by anchoring dendritic tips during cell migration.

    Heiman, Maxwell G; Shaham, Shai

    2009-04-17

    Cells are devices whose structures delimit function. For example, in the nervous system, neuronal and glial shapes dictate paths of information flow. To understand how cells acquire their shapes, we examined the formation of a sense organ in C. elegans. Using time-lapse imaging, we found that sensory dendrites form by stationary anchoring of dendritic tips during cell-body migration. A genetic screen identified DEX-1 and DYF-7, extracellular proteins required for dendritic tip anchoring, which act cooperatively at the time and place of anchoring. DEX-1 and DYF-7 contain, respectively, zonadhesin and zona pellucida domains, and DYF-7 self-associates into multimers important for anchoring. Thus, unlike other dendrites, amphid dendritic tips are positioned by DEX-1 and DYF-7 without the need for long-range guidance cues. In sequence and function, DEX-1 and DYF-7 resemble tectorins, which anchor stereocilia in the inner ear, suggesting that a sensory dendrite anchor may have evolved into part of a mechanosensor. PMID:19344940

  15. Carnosic Acid Prevents Beta-Amyloid-Induced Injury in Human Neuroblastoma SH-SY5Y Cells via the Induction of Autophagy.

    Liu, Jie; Su, Hua; Qu, Qiu-Min

    2016-09-01

    Beta-amyloid (Aβ), the hallmark protein in Alzheimer's disease (AD), induces neurotoxicity that involves oxidative stress and mitochondrial dysfunction, leading to cell death. Carnosic acid (CA), a polyphenolic diterpene isolated from the herb rosemary (Rosemarinus officinalis), was investigated in our study to assess its neuroprotective effect and underlying mechanism against Aβ-induced injury in human neuroblastoma SH-SY5Y cells. We found that CA pretreatment alleviated the Aβ25-35-induced loss of cell viability, inhibited both Aβ1-42 accumulation and tau hyperphosphorylation, reduced reactive oxygen species generation, and maintained the mitochondrial membrane potential. Moreover, CA increased the microtubule-associated protein light chain 3 (LC3)-II/I ratio and decreased SQSTM1(p62), indicating that CA could induce autophagy. Autophagy inhibitor 3-methyladenine (3-MA) attenuated the neuroprotective effect of CA, suggesting that autophagy was involved in the neuroprotection of CA. It was also observed that CA activated AMP-activated protein kinase (AMPK) but inhibited mammalian target of rapamycin (mTOR). Furthermore, blocking AMPK with si-AMPKα successfully inhibited the upregulation of LC3-II/I, prevented the downregulation of phosphorylation of mTOR and SQSTM1(p62), indicating that CA induced autophagy in SH-SY5Y cells via the activation of AMPK. These results suggested that CA might be a potential agent for preventing AD. PMID:27168327

  16. N-Acetylcysteine Prevents Spatial Memory Impairment Induced by Chronic Early Postnatal Glutaric Acid and Lipopolysaccharide in Rat Pups

    Rodrigues, Fernanda S.; Souza, Mauren A.; Magni, Danieli V.; Ferreira, Ana Paula O.; Mota, Bibiana C.; Cardoso, Andreia M.; Paim, Mariana; Xavier, Léder L.; Ferreira, Juliano; Schetinger, Maria Rosa C.; Da Costa, Jaderson C.; Royes, Luiz Fernando F.; Fighera, Michele R.

    2013-01-01

    Background and Aims Glutaric aciduria type I (GA-I) is characterized by accumulation of glutaric acid (GA) and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS) in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC) on theses markers. Methods Rat pups were injected with GA (5umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life), and were supplemented with NAC (150mg/kg/day; intragastric gavage; for the same period). LPS (2mg/kg; E.coli 055 B5) or vehicle (saline 0.9%) was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed. Results GA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance) content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers. Conclusions These results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could represent a possible

  17. N-acetylcysteine prevents spatial memory impairment induced by chronic early postnatal glutaric acid and lipopolysaccharide in rat pups.

    Fernanda S Rodrigues

    Full Text Available BACKGROUND AND AIMS: Glutaric aciduria type I (GA-I is characterized by accumulation of glutaric acid (GA and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC on theses markers. METHODS: Rat pups were injected with GA (5 umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life, and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period. LPS (2 mg/kg; E.coli 055 B5 or vehicle (saline 0.9% was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed. RESULTS: GA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers. CONCLUSIONS: These results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could

  18. Nitric oxide donors prevent while the nitric oxide synthase inhibitor L-NAME increases arachidonic acid plus CYP2E1-dependent toxicity

    Polyunsaturated fatty acids such as arachidonic acid (AA) play an important role in alcohol-induced liver injury. AA promotes toxicity in rat hepatocytes with high levels of cytochrome P4502E1 and in HepG2 E47 cells which express CYP2E1. Nitric oxide (NO) participates in the regulation of various cell activities as well as in cytotoxic events. NO may act as a protectant against cytotoxic stress or may enhance cytotoxicity when produced at elevated concentrations. The goal of the current study was to evaluate the effect of endogenously or exogenously produced NO on AA toxicity in liver cells with high expression of CYP2E1 and assess possible mechanisms for its actions. Pyrazole-induced rat hepatocytes or HepG2 cells expressing CYP2E1 were treated with AA in the presence or absence of an inhibitor of nitric oxide synthase L-N G-Nitroarginine Methylester (L-NAME) or the NO donors S-nitroso-N-acetylpenicillamine (SNAP), and (Z)-1-[-(2-aminoethyl)-N-(2-aminoethyl)]diazen-1-ium-1,2-diolate (DETA-NONO). AA decreased cell viability from 100% to 48 ± 6% after treatment for 48 h. In the presence of L-NAME, viability was further lowered to 23 ± 5%, while, SNAP or DETA-NONO increased viability to 66 ± 8 or 71 ± 6%. The L-NAME potentiated toxicity was primarily necrotic in nature. L-NAME did not affect CYP2E1 activity or CYP2E1 content. SNAP significantly lowered CYP2E1 activity but not protein. AA treatment increased lipid peroxidation and lowered GSH levels. L-NAME potentiated while SNAP prevented these changes. Thus, L-NAME increased, while NO donors decreased AA-induced oxidative stress. Antioxidants prevented the L-NAME potentiation of AA toxicity. Damage to mitochondria by AA was shown by a decline in the mitochondrial membrane potential (MMP). L-NAME potentiated this decline in MMP in association with its increase in AA-induced oxidative stress and toxicity. NO donors decreased this decline in MMP in association with their decrease in AA-induced oxidative stress and

  19. EGFR Inhibition Blocks Palmitic Acid-induced inflammation in cardiomyocytes and Prevents Hyperlipidemia-induced Cardiac Injury in Mice.

    Li, Weixin; Fang, Qilu; Zhong, Peng; Chen, Lingfeng; Wang, Lintao; Zhang, Yali; Wang, Jun; Li, Xiaokun; Wang, Yi; Wang, Jingying; Liang, Guang

    2016-01-01

    Obesity is often associated with increased risk of cardiovascular diseases. Previous studies suggest that epidermal growth factor receptor (EGFR) antagonism may be effective for the treatment of angiotensin II-induced cardiac hypertrophy and diabetic cardiomyopathy. This study was performed to demonstrate if EGFR plays a role in the pathogenesis of hyperlipidemia/obesity-related cardiac injuries. The in vivo studies using both wild type (WT) and apolipoprotein E (ApoE) knockout mice fed with high fat diet (HFD) showed the beneficial effects of small-molecule EGFR inhibitors, AG1478 and 542, against obesity-induced myocardial injury. Administration of AG1478 and 542 significantly reduced myocardial inflammation, fibrosis, apoptosis, and dysfunction in both two obese mouse models. In vitro, EGFR signaling was blocked by either siRNA silencing or small-molecule EGFR inhibitors in palmitic acid (PA)-stimulated cardiomyocytes. EGFR inhibition attenuated PA-induced inflammatory response and apoptosis in H9C2 cells. Furthermore, we found that PA-induced EGFR activation was mediated by the upstream TLR4 and c-Src. This study has confirmed the detrimental effect of EGFR activation in the pathogenesis of obesity-induced cardiac inflammatory injuries in experimental mice, and has demonstrated the TLR4/c-Src-mediated mechanisms for PA-induced EGFR activation. Our data suggest that EGFR may be a therapeutic target for obesity-related cardiovascular diseases. PMID:27087279

  20. Glycyrrhizic acid pretreatment prevents sepsis-induced acute kidney injury via suppressing inflammation, apoptosis and oxidative stress.

    Zhao, Hongyu; Liu, Zhenning; Shen, Haitao; Jin, Shuai; Zhang, Shun

    2016-06-15

    Glycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. The aim of our study was to investigate the molecular mechanism involved in the protective effects of GA in lipopolysaccharide (LPS) stimulated rat mesangial cells (HBZY-1) and septic rats. Sepsis model was established by injection of 5mg/kg LPS in rats or incubation with 1μg/ml LPS for 24h in HBZY-1 cells. A variety of molecular biological experiments were carried out to assess the effects of GA on inflammation, apoptosis, and oxidative stress. First we found that GA alleviated sepsis-induced kidney injury in vivo. Furthermore, GA suppressed inflammatory response in vivo and in vitro. Additionally, GA inhibited cell apoptosis and the changes in expressions of apoptosis related proteins induced by LPS. Moreover, GA markedly inhibited oxidative stress induced by LPS via activation of ERK signaling pathway. Finally GA could inhibit the activation of NF-κ B induced by LPS. Our present study indicates that GA has a protective effect against sepsis-induced inflammatory response, apoptosis, and oxidative stress damage, which provides a molecular basis for a new medical treatment of septic acute kidney injury. PMID:27063444

  1. Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury

    Velat Şen

    2014-01-01

    Full Text Available The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300–350 g were allocated randomly to four groups. In group 1, normal saline (NS was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI was found to be associated with increased malondialdehyde (MDA, total oxidant activity (TOA, oxidative stress index (OSI, and decreased total antioxidant capacity (TAC. Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P<0.05. The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

  2. Preventive effects of dexmedetomidine on the liver in a rat model of acid-induced acute lung injury.

    Sen, Velat; Güzel, Abdulmenap; Şen, Hadice Selimoğlu; Ece, Aydın; Uluca, Unal; Söker, Sevda; Doğan, Erdal; Kaplan, İbrahim; Deveci, Engin

    2014-01-01

    The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300-350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI. PMID:25165710

  3. Neutralization/prevention of acid rock drainage using mixtures of alkaline by-products and sulfidic mine wastes.

    Alakangas, Lena; Andersson, Elin; Mueller, Seth

    2013-11-01

    Backfilling of open pit with sulfidic waste rock followed by inundation is a common method for reducing sulfide oxidation after mine closure. This approach can be complemented by mixing the waste rock with alkaline materials from pulp and steel mills to increase the system's neutralization potential. Leachates from 1 m3 tanks containing sulfide-rich (ca.30 wt %) waste rock formed under dry and water saturated conditions under laboratory conditions were characterized and compared to those formed from mixtures. The waste rock leachate produced an acidic leachate (pHhigh concentrations of As (65 mg/L), Cu (6 mg/L), and Zn (150 mg/L) after 258 days. The leachate from water-saturated waste rock had lower concentrations of As and Cu (9). The decrease of elemental concentration in the leachate was most pronounced for Pb and Zn, while Al and S were relatively high. Overall, the results obtained were promising and suggest that alkaline by-products could be useful additives for minimizing ARD formation. PMID:23740301

  4. Fumaric acid esters prevent the NLRP3 inflammasome-mediated and ATP-triggered pyroptosis of differentiated THP-1 cells.

    Miglio, Gianluca; Veglia, Eleonora; Fantozzi, Roberto

    2015-09-01

    Fumaric acid esters (FAEs) exert therapeutic effects in patients with psoriasis and multiple sclerosis, however their mode of action remains elusive. Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death, mediated by the activation of inflammasomes. To understand the pharmacological basis of the therapeutic effects of FAEs, the anti-pyroptotic activity of dimethyl fumarate (DMF) and its hydrolysis metabolite monomethyl fumarate (MMF) was studied in a model of NLRP3 inflammasome-mediated pyroptosis of human macrophages. Phorbol myristate acetate-differentiated THP-1 cells were exposed to lipopolysaccharide (5 μg/ml; 4h), then pulsed with ATP (5mM; 1h). MMF, DMF, or parthenolide (positive control) were added 1h before the ATP pulse. The pyroptotic cell death was evaluated by morphological examination and quantified by measuring the lactate dehydrogenase leakage. The ATP-triggered death of THP-1 cells (60.4 ± 4.0%) was significantly (Pmolecular cascade leading to cell death. These results indicate that FAEs are endowed with anti-pyroptotic activity, which may contribute to their therapeutic effects. PMID:26096886

  5. N-acetylcysteine and/or ascorbic acid versus placebo to prevent contrast-induced nephropathy in patients undergoing elective cardiac catheterization: The NAPCIN trial; A single-center, prospective, randomized trial

    Mohammed Habib; Alaa Hillis; Amen Hammad

    2016-01-01

    Several protective measures have been described to prevent contrast-induced nephropathy (CIN). This study is aimed to evaluate the effect of a high dose of N-acetylcysteine (NAC) plus hydration, a low dose of NAC plus ascorbic acid and hydration or hydration alone on the prevention of CIN in high-risk patients undergoing elective coronary artery intervention. We conducted a randomized, prospective, placebo-controlled trial of 105 high-risk patients undergoing elective cardiac catheterization....

  6. CD8+ CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells1

    Yamazaki, Sayuri; Dudziak, Diana; Heidkamp, Gordon F; Fiorese, Christopher; Bonito, Anthony J.; Inaba, Kayo; Nussenzweig, Michel C.; Steinman, Ralph M.

    2008-01-01

    Foxp3+CD25+CD4+ regulatory T cells (T reg) mediate immunological self-tolerance and suppress immune responses. A subset of dendritic cells (DCs) in the intestine is specialized to induce T reg in a transforming growth factor (TGF)-β and retinoic acid (RA) dependent manner to allow for oral tolerance. Here we compare two major DC subsets from mouse spleen. We find that CD8+ DEC-205/CD205+ DCs, but not the major fraction of CD8− dendritic cell inhibitory receptor-2 (DCIR2)+ DCs, induce function...

  7. Preventive effect of a pectic polysaccharide of the common cranberry Vaccinium oxycoccos L. on acetic acid-induced colitis in mice

    Sergey V Popov; Pavel A Markov; Ida R Nikitina; Sergey Petrishev; Vasily Smirnov; Yury S Ovodov

    2006-01-01

    AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccinium oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis.METHODS: Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4%Evans blue passage after i.p. injection of 0.05 mol/L acetic acid.RESULTS: In the mice treated with OP, colonic macroscopic scores (1.1 ± 0.4 vs 2.7, P < 0.01) and the total square area of damage (10 ± 2 vs 21 ± 7, P < 0.01)were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42 ± 11 vs 112 ± 40, P < 0.01) and enhance the amount of mucus of colitis mice (0.9 ± 0.1 vs 0.4 ± 0.1, P < 0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6 ± 0.7 vs 5.1 ± 0.8, P < 0.01).OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161 ± 34 vs 241 ± 21, P < 0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141 ± 50vs 235 ± 37, P < 0.05).CONCLUSION: Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP,on acetic acid-induced colitis in mice was detected.A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.

  8. PrPSc accumulation in neuronal plasma membranes links Notch-1 activation to dendritic degeneration in prion diseases

    DeArmond Stephen J

    2010-01-01

    Full Text Available Abstract Prion diseases are disorders of protein conformation in which PrPC, the normal cellular conformer, is converted to an abnormal, protease-resistant conformer rPrPSc. Approximately 80% of rPrPSc accumulates in neuronal plasma membranes where it changes their physical properties and profoundly affects membrane functions. In this review we explain how rPrPSc is transported along axons to presynaptic boutons and how we envision the conversion of PrPC to rPrPSc in the postsynaptic membrane. This information is a prerequisite to the second half of this review in which we present evidence that rPrPSc accumulation in synaptic regions links Notch-1 signaling with the dendritic degeneration. The hypothesis that the Notch-1 intracellular domain, NICD, is involved in prion disease was tested by treating prion-infected mice with the γ-secretase inhibitor (GSI LY411575, with quinacrine (Qa, and with the combination of GSI + Qa. Surprisingly, treatment with GSI alone markedly decreased NICD but did not prevent dendritic degeneration. Qa alone produced near normal dendritic trees. The combined GSI + Qa treatment resulted in a richer dendritic tree than in controls. We speculate that treatment with GSI alone inhibited both stimulators and inhibitors of dendritic growth. With the combined GSI + Qa treatment, Qa modulated the effect of GSI perhaps by destabilizing membrane rafts. GSI + Qa decreased PrPSc in the neocortex and the hippocampus by 95%, but only by 50% in the thalamus where disease was begun by intrathalamic inoculation of prions. The results of this study indicate that GSI + Qa work synergistically to prevent dendrite degeneration and to block formation of PrPSc.

  9. Intraperitoneal Alpha-Lipoic Acid to prevent neural damage after crush injury to the rat sciatic nerve

    Ozbag Davut

    2009-01-01

    Full Text Available Abstract Objective Crush injury to the sciatic nerve causes oxidative stress. Alfa Lipoic acid (a-LA is a neuroprotective metabolic antioxidant. This study was designed to investigate the antioxidant effects of pretreatment with a-LA on the crush injury of rat sciatic nerve. Methods Forty rats were randomized into four groups. Group I and Group II received saline (2 ml, intraperitoneally and a-LA (100 mg/kg, 2 ml, intraperitoneally in the groups III and IV at the 24 and 1 hour prior to the crush injury. In groups II, III and IV, the left sciatic nerve was exposed and compressed for 60 seconds with a jeweler's forceps. In Group I (n = 10, the sciatic nerve was explored but not crushed. In all groups of rats, superoxide dismutase (SOD and catalase (CAT activities, as well as malondialdehyde (MDA levels were measured in samples of sciatic nerve tissue. Results Compared to Group I, Group II had significantly decreased tissue SOD and CAT activities and elevated MDA levels indicating crush injury (p < 0.05. In the a-LA treatment groups (groups III and IV, tissue CAT and SOD activities were significantly increased and MDA levels significantly decreased at the first hour (p < 0.05 and on the 3rd day (p < 0.05. There was no significant difference between a-LA treatment groups (p > 0.05. Conclusion A-LA administered before crush injury of the sciatic nerve showed significant protective effects against crush injury by decreasing the oxidative stress. A-LA should be considered in the treatment of peripheral nerve injuries, but further studies are needed to explain the mechanism of its neuroprotective effects.

  10. Prevention of tri-nitrobenzene of sulfonic acid-induced colitis in chicken by using extract of Aloe vera

    Motamed Elsayed Mahmoud

    Full Text Available Aim: Aloe vera, species of succulent plant in the genus Aloe, has multiple clinical activities and used routinely to accelerate wound healing. The present study was designed to investigate the anti-inflammatory effect of Aloe vera extracts (AVE in vitro and in vivo. Materials and Methods: The effect of crude AVE on inducible nitric oxide production by LPS/IFNg-stimulated cultured macrophages was evaluated. The therapeutic effect of administering crude Aloe vera extracts (100 mg/kg b.w. on the development of tri-nitrobenzene of sulfonic acid (TNBS-induced colitis (40 mg/kg b. w. in chicken was also investigated. Chicken is a valuable model for this purpose because it showed preference to bitter taste of Aloe vera. Diverse clinical pictures of the colitis including weight loss, diarrhea and histopathological changes were evaluated. Results: Nitrite production by LPS/IFNg-stimulated macrophages was maximally reduced by adding of AVE (100 μg/ml. This result suggests a direct inhibitory effect of AVE on the inflammatory cells. Chicks treated orally with AVE showed improvement of the histological signs with no inflammatory cell infiltrates and reduction of myeloperoxidase (MPO activities when compared with colitis control group. AVE pretreatment ameliorated significantly the clinical and histopathological severity of the TNBS-induced colitis; decreased body weight loss and diarrhea and increased survival. Conclusion: It was concluded that oral administration of AVE represents a valuable therapeutic approach for the treatment of colitis in chicken. [Vet. World 2012; 5(8.000: 469-476

  11. Protocatechuic Acid Attenuates Osteoclastogenesis by Downregulating JNK/c-Fos/NFATc1 Signaling and Prevents Inflammatory Bone Loss in Mice.

    Park, Sun-Hyang; Kim, Ju-Young; Cheon, Yoon-Hee; Baek, Jong Min; Ahn, Sung-Jun; Yoon, Kwon-Ha; Lee, Myeung Su; Oh, Jaemin

    2016-04-01

    Protocatechuic acid (PCA) plays a critical role in nutritional metabolism; it is a major metabolite of anthocyanins, which are flavonoids with a range of health benefits. PCA has a variety of biological activities including anti-oxidant, antiinflammatory, anti-apoptosis, and anti-microbial activities. However, the pharmacological effect of PCA, especially on osteoclastogenesis, remains unknown. We examined the effect of PCA on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption. PCA dose-dependently inhibited RANKL-induced osteoclast differentiation in mouse bone marrow macrophages (BMMs) and suppressed the bone-resorbing activity of mature osteoclasts. At the molecular level, PCA suppressed RANKL-induced phosphorylation of JNK among MAPKs only, without significantly affecting the early signaling pathway. PCA also suppressed RANKL-stimulated expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1) at the mRNA and protein levels, without altering c-Fos mRNA expression. Additionally, PCA down-regulated the expression of downstream osteoclastogenesis-related genes including β3-integrin, DC-STAMP, OC-STAMP, Atp6v0d2, CTR, and CtsK. Mice treated with PCA efficiently recovered from lipopolysaccharide-induced bone loss in vivo. Thus, PCA inhibits RANKL-induced osteoclast differentiation and function by suppressing JNK signaling, c-Fos stability, and expression of osteoclastic marker genes. These results suggest that PCA could be useful in treatment of inflammatory bone disorders. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26792397

  12. Asymmetry in signal propagation between the soma and dendrites plays a key role in determining dendritic excitability in motoneurons.

    Hojeong Kim

    Full Text Available It is widely recognized that propagation of electrophysiological signals between the soma and dendrites of neurons differs depending on direction, i.e. it is asymmetric. How this asymmetry influences the activation of voltage-gated dendritic channels, and consequent neuronal behavior, remains unclear. Based on the analysis of asymmetry in several types of motoneurons, we extended our previous methodology for reducing a fully reconstructed motoneuron model to a two-compartment representation that preserved asymmetric signal propagation. The reduced models accurately replicated the dendritic excitability and the dynamics of the anatomical model involving a persistent inward current (PIC dispersed over the dendrites. The relationship between asymmetric signal propagation and dendritic excitability was investigated using the reduced models while varying the asymmetry in signal propagation between the soma and the dendrite with PIC density constant. We found that increases in signal attenuation from soma to dendrites increased the activation threshold of a PIC (hypo-excitability, whereas increases in signal attenuation from dendrites to soma decreased the activation threshold of a PIC (hyper-excitability. These effects were so strong that reversing the asymmetry in the soma-to-dendrite vs. dendrite-to-soma attenuation, reversed the correlation between PIC threshold and distance of this current source from the soma. We propose the tight relation of the asymmetric signal propagation to the input resistance in the dendrites as a mechanism underlying the influence of the asymmetric signal propagation on the dendritic excitability. All these results emphasize the importance of maintaining the physiological asymmetry in dendritic signaling not only for normal function of the cells but also for biophysically realistic simulations of dendritic excitability.

  13. Inorganic arsenic impairs differentiation and functions of human dendritic cells

    Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

  14. Inorganic arsenic impairs differentiation and functions of human dendritic cells

    Macoch, Mélinda; Morzadec, Claudie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

    2013-01-15

    Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

  15. A highly active water-soluble cross-coupling catalyst based on dendritic polyglycerol N-heterocyclic carbene palladium complexes.

    Meise, Markus; Haag, Rainer

    2008-01-01

    A new water-soluble polyglycerol derivative functionalized with N-heterocyclic carbene palladium complexes was prepared and applied as catalyst for Suzuki cross-coupling reactions in water. The complex displays a metal loading of around 65 metal centers per dendrimeric molecule, which is estimated to contain 130 chelating groups and thus corresponds approximately to the formation of 2:1 NHC/metal complexes. Monomeric analogues were also synthesized to validate the reactivity of the dendritic catalyst. Both types of catalysts were tested with various aryl bromides and arylboronic acids. Turnover frequencies of up to 2586 h(-1) at 80 degrees C were observed with the dendritic catalyst along with turnover numbers of up to 59 000, which are among the highest turnover numbers reported for polymer-supported catalysts in neat water. The dendritic catalyst could be used (reused) in five consecutive reactions without loss in activity. PMID:18702166

  16. Topical Hyaluronic Acid vs. Standard of Care for the Prevention of Radiation Dermatitis After Adjuvant Radiotherapy for Breast Cancer: Single-Blind Randomized Phase III Clinical Trial

    Purpose: To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of ≥Grade 2 radiation dermatitis after adjuvant breast radiation compared with best supportive care. Methods and Materials: Women with breast cancer who had undergone lumpectomy and were to receive whole-breast radiotherapy to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid–based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel on the medial half or the lateral half of the irradiated breast and to use the control gel on the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of ≥Grade 2 dermatitis. Results: The study closed early on the basis of a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed a significantly higher rate of ≥Grade 2 dermatitis than did skin treated with petrolatum gel: 61.5% (40/65) vs. 47.7% (31/65) (p = 0.027). Only 1ne patient developed Grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than in that treated with petrolatum gel at the end of radiotherapy (42% vs. 14%, p = 0.003). Conclusion: We found no benefit from the use of a topical hyaluronic acid–based gel for reducing the development of ≥Grade 2 dermatitis after adjuvant radiotherapy for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid–based gel in controlling radiation dermatitis symptoms after they develop

  17. Sleeping dendrites: fiber-optic measurements of dendritic calcium activity in freely moving and sleeping animals

    Julie Seibt

    2014-03-01

    Full Text Available Dendrites are the post-synaptic sites of most excitatory and inhibitory synapses in the brain, making them the main location of cortical information processing and synaptic plasticity. Although current hypotheses suggest a central role for sleep in proper cognitive function and brain plasticity, virtually nothing is known about changes in dendritic activity across the sleep-wake cycle and how waking experience modifies this activity. To start addressing these questions, we developed a method that allows long-term recordings of EEGs/EMG combined with in vivo cortical calcium (Ca2+ activity in freely moving and sleeping rats. We measured Ca2+ activity from populations of dendrites of layer (L 5 pyramidal neurons (n = 13 rats that we compared with Ca2+ activity from populations of neurons in L2/3 (n = 11 rats. L5 and L2/3 neurons were labelled using bolus injection of OGB1-AM or GCaMP6 (1. Ca2+ signals were detected using a fiber-optic system (cannula diameter = 400µm, transmitting the changes in fluorescence to a photodiode. Ca2+ fluctuations could then be correlated with ongoing changes in brain oscillatory activity during 5 major brain states: active wake [AW], quiet wake [QW], NREM, REM and NREM-REM transition (or intermediate state, [IS]. Our Ca2+ recordings show large transients in L5 dendrites and L2/3 neurons that oscillate predominantly at frequencies In summary, we show that this technique is successful in monitoring fluctuations in ongoing dendritic Ca2+ activity during natural brain states and allows, in principle, to combine behavioral measurement with imaging from various brain regions (e.g. deep structures in freely behaving animals. Using this method, we show that Ca2+ transients from populations of L2/3 neurons and L5 dendrites are deferentially regulated across the sleep/wake cycle, with dendritic activity being the highest during the IS sleep. Our correlation analysis suggests that specific sleep EEG activity during NREM and IS

  18. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis.

    Misra, Mala; Edmund, Hendia; Ennis, Darragh; Schlueter, Marissa A; Marot, Jessica E; Tambasco, Janet; Barlow, Ida; Sigurbjornsdottir, Sara; Mathew, Renjith; Vallés, Ana Maria; Wojciech, Waldemar; Roth, Siegfried; Davis, Ilan; Leptin, Maria; Gavis, Elizabeth R

    2016-01-01

    Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling. PMID:27260999

  19. Evaluating Local Primary Dendrite Arm Spacing Characterization Techniques Using Synthetic Directionally Solidified Dendritic Microstructures

    Tschopp, Mark A.; Miller, Jonathan D.; Oppedal, Andrew L.; Solanki, Kiran N.

    2015-10-01

    Microstructure characterization continues to play an important bridge to understanding why particular processing routes or parameters affect the properties of materials. This statement certainly holds true in the case of directionally solidified dendritic microstructures, where characterizing the primary dendrite arm spacing is vital to developing the process-structure-property relationships that can lead to the design and optimization of processing routes for defined properties. In this work, four series of simulations were used to examine the capability of a few Voronoi-based techniques to capture local microstructure statistics (primary dendrite arm spacing and coordination number) in controlled (synthetically generated) microstructures. These simulations used both cubic and hexagonal microstructures with varying degrees of disorder (noise) to study the effects of length scale, base microstructure, microstructure variability, and technique parameters on the local PDAS distribution, local coordination number distribution, bulk PDAS, and bulk coordination number. The Voronoi tesselation technique with a polygon-side-length criterion correctly characterized the known synthetic microstructures. By systematically studying the different techniques for quantifying local primary dendrite arm spacings, we have evaluated their capability to capture this important microstructure feature in different dendritic microstructures, which can be an important step for experimentally correlating with both processing and properties in single crystal nickel-based superalloys.

  20. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

    Misra, Mala; Edmund, Hendia; Ennis, Darragh; Schlueter, Marissa A.; Marot, Jessica E.; Tambasco, Janet; Barlow, Ida; Sigurbjornsdottir, Sara; Mathew, Renjith; Vallés, Ana Maria; Wojciech, Waldemar; Roth, Siegfried; Davis, Ilan; Leptin, Maria; Gavis, Elizabeth R.

    2016-01-01

    Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling. PMID:27260999

  1. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

    Mala Misra

    2016-08-01

    Full Text Available Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling.

  2. Simulation of dendritic growth reveals necessary and sufficient parameters to describe the shapes of dendritic trees

    Trottier, Olivier; Ganguly, Sujoy; Bowne-Anderson, Hugo; Liang, Xin; Howard, Jonathon

    For the last 120 years, the development of neuronal shapes has been of great interest to the scientific community. Over the last 30 years, significant work has been done on the molecular processes responsible for dendritic development. In our ongoing research, we use the class IV sensory neurons of the Drosophila melanogaster larva as a model system to understand the growth of dendritic arbors. Our main goal is to elucidate the mechanisms that the neuron uses to determine the shape of its dendritic tree. We have observed the development of the class IV neuron's dendritic tree in the larval stage and have concluded that morphogenesis is defined by 3 distinct processes: 1) branch growth, 2) branching and 3) branch retraction. As the first step towards understanding dendritic growth, we have implemented these three processes in a computational model. Our simulations are able to reproduce the branch length distribution, number of branches and fractal dimension of the class IV neurons for a small range of parameters.

  3. Dendritic nanocomposite for delivery of antibacterial agent

    Pureti Madhu Kumar; PSrinivasa Babu; Shaik Rasheed; Ramadoss Karthikeyan

    2013-01-01

    Objective: To develop and explore the use of PEGylated poly (propylene imine) dendritic architecture for the delivery of an anti bacterial bioactive, Trimethoprim. Methods: For this study, PEGylated poly(propylene imine) dendritic architecture was synthesized and loaded with Trimethoprim and targeted to the resistant producing strains of both gram positive and gram negative. The antibacterial activity was carried out by agar well-diffusion method to compare zone of inhibition with standard drug and plain PPI dendrimer. Results: The study showed that the Trimethoprim loaded dendrimer has significant antibacterial activity than the plain PPI dendrimer, but standard drug was not shown zone of inhibition upon both microorganisms butKlebsiella pneumoniae (K. pneumoniae) the pure drug showed activity. Conclusions: In this study antibacterial activity of synthesized system is also relatively safer and holds potential to deliver any other antibacterial agent to the resistant producing strains.

  4. Dendritic Cells for SYN Scan Detection

    Greensmith, Julie

    2010-01-01

    Artificial immune systems have previously been applied to the problem of intrusion detection. The aim of this research is to develop an intrusion detection system based on the function of Dendritic Cells (DCs). DCs are antigen presenting cells and key to activation of the human immune system, behaviour which has been abstracted to form the Dendritic Cell Algorithm (DCA). In algorithmic terms, individual DCs perform multi-sensor data fusion, asynchronously correlating the the fused data signals with a secondary data stream. Aggregate output of a population of cells, is analysed and forms the basis of an anomaly detection system. In this paper the DCA is applied to the detection of outgoing port scans using TCP SYN packets. Results show that detection can be achieved with the DCA, yet some false positives can be encountered when simultaneously scanning and using other network services. Suggestions are made for using adaptive signals to alleviate this uncovered problem.

  5. Preventing stroke

    Stroke - prevention; CVA - prevention; cerebral vascular accident - prevention; TIA - prevention, transient ischemic attack - prevention ... A stroke occurs when the blood supply is cut off to any part of the brain. A stroke is ...

  6. Pulmonary dendritic cells: thinking globally, acting locally

    Randall, Troy D.

    2010-01-01

    The phrase “think globally, act locally” was coined in the early 1970s and directed individuals to clean up their local environment with the ultimate goal of improving the health of the entire planet. Several recent studies indicate that similar considerations apply to the immune system, in which small numbers of leukocytes, such as pulmonary dendritic cells, can modify the local immune environment in the lung and promote a positive outcome for the organism.

  7. Dendritic cells and aging: consequences for autoimmunity

    Agrawal, Anshu; Sridharan, Aishwarya; Prakash, Sangeetha; Agrawal, Harsh

    2012-01-01

    The immune system has evolved to mount immune responses against foreign pathogens and to remain silent against self-antigens. A balance between immunity and tolerance is required as any disturbance may result in chronic inflammation or autoimmunity. Dendritic cells (DCs) actively participate in maintaining this balance. Under steady-state conditions, DCs remain in an immature state and do not mount an immune response against circulating self-antigens in the periphery, which maintains a state ...

  8. Plasmacytoid Dendritic Cells: From Heart to Vessels

    Rosalinda Sorrentino; Silvana Morello; Aldo Pinto

    2010-01-01

    Cardiovascular diseases, formerly only attributed to the alterations of the stromal component, are now recognized as immune-based pathologies. Plasmacytoid Dendritic Cells (pDCs) are important immune orchestrators in heart and vessels. They highly produce IFN type I that promote the polarization of T cells towards a Th1 phenotype; however, pDCs can also participate to suppressive networks via the recruitment of T regulatory cells that downmodulate proinflammatory responses. pDCs populate the ...

  9. Harnessing dendritic cells in inflammatory skin diseases

    Chu, Chung-Ching; di Meglio, Paola; Nestle, Frank O

    2011-01-01

    The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-de...

  10. Follicular dendritic cells in health and disease

    El Shikh, Mohey Eldin M.; Costantino ePitzalis

    2012-01-01

    Follicular dendritic cells (FDCs) are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags) in the form of highly immunogenic immune complexes (ICs) consisting of Ag plus specific antibody (Ab) and/or complement proteins. FDCs multimerise Ags and present them polyvalently to B cells in periodically arranged arrays that extensively crosslink the B...

  11. Follicular dendritic cells in health and disease

    El Shikh, Mohey Eldin M.; Pitzalis, Costantino

    2012-01-01

    Follicular dendritic cells (FDCs) are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B-cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags) in the form of highly immunogenic immune complexes (ICs) consisting of Ag plus specific antibody (Ab) and/or complement proteins. FDCs multimerize Ags and present them polyvalently to B-cells in periodically arranged arrays that extensively crosslink the B...

  12. Role of Dendritic Cells in Immune Dysfunction

    Savary, Cherylyn A.

    1997-01-01

    Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

  13. SKIN DENDRITIC CELLS: ACTIVATION, MATURATION AND MIGRATION

    Eaton, Laura

    2012-01-01

    Langerhans’ cells (LC) are the dendritic cells (DC) of the epidermis and, as sentinels of the immune system, act as a bridge between the innate and adaptive immune responses. When LC, and other DC, recognise an antigen or pathogen they mature and are stimulated to migrate to the lymph nodes, where they orchestrate immune responses. Pathogen derived toll-like receptor (TLR) ligands, and chemical allergens, are recognised as being potentially harmful and stimulate LC to mobilise and mature. Cyt...

  14. Bacterial Probiotic Modulation of Dendritic Cells

    Drakes, Maureen; Blanchard, Thomas; Czinn, Steven

    2004-01-01

    Intestinal dendritic cells are continually exposed to ingested microorganisms and high concentrations of endogenous bacterial flora. These cells can be activated by infectious agents and other stimuli to induce T-cell responses and to produce chemokines which recruit other cells to the local environment. Bacterial probiotics are of increasing use against intestinal disorders such as inflammatory bowel disease. They act as nonpathogenic stimuli within the gut to regain immunologic quiescence. ...

  15. Imaging membrane potential in dendritic spines

    Nuriya, Mutsuo; Jiang, Jiang; Nemet, Boaz; Eisenthal, Kenneth B.; Yuste, Rafael

    2006-01-01

    Dendritic spines mediate most excitatory inputs in the brain. Although it is clear that spines compartmentalize calcium, it is still unknown what role, if any, they play in integrating synaptic inputs. To investigate the electrical function of spines directly, we used second harmonic generation (SHG) imaging of membrane potential in pyramidal neurons from hippocampal cultures and neocortical brain slices. With FM 4-64 as an intracellular SHG chromophore, we imaged membrane potential in the so...

  16. Ellagic acid inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and prevents atheroma formation in streptozotocin-induced diabetic rats.

    Rani, Uma P; Kesavan, Rushendhiran; Ganugula, Raghu; Avaneesh, T; Kumar, Uday P; Reddy, G Bhanuprakash; Dixit, Madhulika

    2013-11-01

    Plant-derived polyphenolic compounds have beneficial health effects. In the present study, we determined the ability of ellagic acid (EA) to prevent platelet-derived growth factor-BB (PDGF-BB)-induced proliferation of primary cultures of rat aortic smooth muscle cells (RASMCs). We also determined the ability of EA to prevent atherosclerosis in streptozotocin-induced diabetic rats. Proliferation of cells was measured via Alamar Blue assay and through propidium iodide-based cell cycle analysis in flow cytometer. Reactive oxygen species (ROS) were measured via 2',7'-dichlorofluorescin diacetate and Amplex red methods. Expression of proliferation markers and activation of kinases were assessed by immunoblot analysis. Cotreatment of primary cultures of RASMCs with 25 μmol/L of EA significantly reduced PDGF-BB (20 ng/ml)-induced proliferation by blocking S-phase entry. EA effectively blocked PDGF receptor-β (PDGFR-β) tyrosine phosphorylation, generation of intracellular ROS and downstream activation of extracellular signal-regulated kinase 1/2. It also blocked PDGF-BB-induced expression of cyclin D1. Computational molecular docking of EA with the PDGFR-β-PDGF-BB complex revealed two putative inhibitor binding sites which showed similar binding energies with the known PDGFR-β inhibitor AG1295. In diabetic rats, supplementation of diet with 2% EA significantly blocked diabetes-induced medial thickness, and lipid and collagen deposition in the arch of aorta. These were assessed through haematoxylin and eosin, Oil Red O and Masson's trichome staining, respectively. EA treatment also blocked cyclin D1 expression in medial smooth muscle cells in experimental animals. Thus, EA is effective in reducing atherosclerotic process by blocking proliferation of vascular smooth muscle cells. PMID:23866995

  17. Long-term omega-3 fatty acid supplementation prevents expression changes in cochlear homocysteine metabolism and ameliorates progressive hearing loss in C57BL/6J mice.

    Martínez-Vega, Raquel; Partearroyo, Teresa; Vallecillo, Néstor; Varela-Moreiras, Gregorio; Pajares, María A; Varela-Nieto, Isabel

    2015-12-01

    Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients well known for their beneficial effects, among others on cognitive development and maintenance, inflammation and oxidative stress. Previous studies have shown an inverse association between high plasma levels of PUFAs and age-related hearing loss, and the relationship between low serum folate and elevated plasma homocysteine levels and hearing loss. Therefore, we used C57BL/6J mice and long-term omega-3 supplementation to evaluate the impact on hearing by analyzing their auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) thresholds. The omega-3 group showed significantly lower ABR hearing thresholds (~25 dB sound pressure level) and higher DPOAE amplitudes in mid-high frequencies when compared to the control group. These changes did not correlate with alterations between groups in plasma homocysteine or serum folate levels as measured by high-performance liquid chromatography and a microbiological method, respectively. Aging in the control group was associated with imbalanced cytokine expression toward increased proinflammatory cytokines as determined by quantitative reverse transcriptase polymerase chain reaction; these changes were prevented by omega-3 supplementation. Genes involved in homocysteine metabolism showed decreased expression during aging of control animals, and only alterations in Bhmt and Cbs were significantly prevented by omega-3 feeding. Western blotting showed that omega-3 supplementation precluded the CBS protein increase detected in 10-month-old controls but also produced an increase in BHMT protein levels. Altogether, the results obtained suggest a long-term protective role of omega-3 supplementation on cochlear metabolism and progression of hearing loss. PMID:26321228

  18. The Isothermal Dendritic Growth Experiment Archive

    Koss, Matthew

    2009-03-01

    The growth of dendrites is governed by the interplay between two simple and familiar processes---the irreversible diffusion of energy, and the reversible work done in the formation of new surface area. To advance our understanding of these processes, NASA sponsored a project that flew on the Space Shuttle Columbia is 1994, 1996, and 1997 to record and analyze benchmark data in an apparent-microgravity ``laboratory.'' In this laboratory, energy transfer by gravity driven convection was essentially eliminated and one could test independently, for the first time, both components of dendritic growth theory. The analysis of this data shows that although the diffusion of energy can be properly accounted for, the results from interfacial physics appear to be in disagreement and alternate models should receive increased attention. Unfortunately, currently and for the foreseeable future, there is no access or financial support to develop and conduct additional experiments of this type. However, the benchmark data of 35mm photonegatives, video, and all supporting instrument data are now available at the IDGE Archive at the College of the Holy Cross. This data may still have considerable relevance to researchers working specifically with dendritic growth, and more generally those working in the synthesis, growth & processing of materials, multiscale computational modeling, pattern formation, and systems far from equilibrium.

  19. Nicotine induces dendritic spine remodeling in cultured hippocampal neurons.

    Oda, Akira; Yamagata, Kanato; Nakagomi, Saya; Uejima, Hiroshi; Wiriyasermkul, Pattama; Ohgaki, Ryuichi; Nagamori, Shushi; Kanai, Yoshikatsu; Tanaka, Hidekazu

    2014-01-01

    Cholinergic neurons in the CNS are involved in synaptic plasticity and cognition. Both muscarinic and nicotinic acetylcholine receptors (nAChRs) influence plasticity and cognitive function. The mechanism underlying nAChR-induced plasticity, however, has remained elusive. Here, we demonstrate morphological changes in dendritic spines following activation of α4β2* nAChRs, which are expressed on glutamatergic pre-synaptic termini of cultured hippocampal neurons. Exposure of the neurons to nicotine resulted in a lateral enlargement of spine heads. This was abolished by dihydro-β-erythroidine, an antagonist of α4β2* nAChRs, but not by α-bungarotoxin, an antagonist of α7 nAChRs. Tetanus toxin or a mixture of 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, antagonists of NMDA- and AMPA-type glutamate receptors, blocked the nicotine-induced spine remodeling. In addition, nicotine exerted full spine-enlarging response in the post-synaptic neuron whose β2 nAChR expression was knocked down. Finally, pre-treatment with nicotine enhanced the Ca(2+)-response of the neurons to glutamate. These data suggest that nicotine influences the activity of glutamatergic neurotransmission through the activation of pre-synaptic α4β2 nAChRs, resulting in the modulation of spinal architecture and responsiveness. The present findings may represent one of the cellular mechanisms underlying cholinergic tuning of brain function. Activation of nicotinic acetylcholine receptors (nAChRs) in brain influences plasticity and cognition. Here, activation of α4β2* nAChRs, which are expressed on glutamatergic presynaptic termini, results in the enlargement of dendritic spines through the modulation of the glutamatergic neurotransmission. The remodeled spinal architecture might be responsible for the change in responsiveness of neural circuitry, leading to cholinergic tuning of brain function. PMID:24117996

  20. Neural pattern formation in networks with dendritic structure

    Bressloff, P. C.; De Souza, B.

    1998-04-01

    We present a detailed analysis of a recently proposed model of neural pattern formation that is based on the combined effect of diffusion along a neuron's dendritic tree and recurrent interactions along axo-dendritic synaptic connections. For concreteness, we consider a one-dimensional array of analog neurons with the dendritic tree idealized as a one-dimensional cable. Linear stability analysis and bifurcation theory together with numerical simulations are used to establish conditions for the onset of a Turing instability leading to the formation of stable spatial patterns of network output activity. It is shown that the presence of dendritic structure can induce dynamic (time-periodic) spatial pattern formation. Moreover, correlations between the dendritic location of a synapse and the relative positions of neurons in the network are shown to result in spatially oscillating patterns of activity along the dendrites of each neuron.

  1. Molecular identity of dendritic voltage-gated sodium channels.

    Lorincz, Andrea; Nusser, Zoltan

    2010-05-14

    Active invasion of the dendritic tree by action potentials (APs) generated in the axon is essential for associative synaptic plasticity and neuronal ensemble formation. In cortical pyramidal cells (PCs), this AP back-propagation is supported by dendritic voltage-gated Na+ (Nav) channels, whose molecular identity is unknown. Using a highly sensitive electron microscopic immunogold technique, we revealed the presence of the Nav1.6 subunit in hippocampal CA1 PC proximal and distal dendrites. Here, the subunit density is lower by a factor of 35 to 80 than that found in axon initial segments. A gradual decrease in Nav1.6 density along the proximodistal axis of the dendritic tree was also detected without any labeling in dendritic spines. Our results reveal the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability. PMID:20466935

  2. Numerical Modeling of Dendrite Growth in Al Alloys

    许庆彦; 柳百成

    2004-01-01

    Dendritic grains are the most often observed microstructure in metals and alloys. In the past decade, more and more attention has been paid to the modeling and simulation of dendritic microstructures. This paper describes a modified diffusion-limited aggregation model to simulate the complex shape of the dendrite grains during metal solidification. The fractal model was used to simulate equiaxed dendrite growth. The fractal dimensions of simulated Al alloy structures range from 1.63-1.88 which compares well with the experimentally-measured fractal dimension of 1.85; therefore, the model accurately predicts not only the dendritic structure morphology, but also the fractal dimension of the dendrite structure formed during solidification.

  3. Special fractal growth of dendrite copper using a hydrothermal method

    Zheng, Yan; Zhang, Zhejuan; Guo, Pingsheng; He, Pingang; Sun, Zhuo

    2011-08-01

    Special fractal dendrite Cu nanostructures have been synthesized through a simple hydrothermal method, and the effects of the volume ratio between glycerol and water and the concentration of H 3PO 3 on the morphologies of dendrite Cu have been studied in detail. The Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM) and X-ray diffraction (XRD) have been used to characterize these Cu products. The results indicate that rhombic diamond and different morphologies of fractal dendrite were prepared because of the accumulation of Cu nuclei based on the diffusion-limited aggregation (DLA) and the nucleation-limited aggregation (NLA) model. Fortunately, symmetrical leaf-like dendrite Cu nanostructures different from Cu dendrites reported before have been obtained. Additionally, an explanation for the growth of fractal dendrite Cu has been discussed carefully.

  4. Vitamines en visvetzuren ter preventie van hart- en vaatziekten: Gezondmakers uit potjes en flesjes T2 = Health from jars and bottles. Vitamins and fish oil fatty acids for prevention of cardiovascular diseases

    Severs, A.H.; Bouterse-van Haaren, M.R.T.

    2000-01-01

    A high dietary intake of antioxidants ascorbic acid, tocopherol and beta-carotene and 1 or 2 servings of fish per week is associated with a lower risk of coronary heart diseases, but the 'evidence' for a preventive effect still has not been produced. A raised homocysteine level can be lowered with f

  5. Macroporous carbon decorated with dendritic platinum nanoparticles: one-step synthesis and electrocatalytic properties

    Yu, Xueqing; Zhang, Yufan; Guo, Liping; Wang, Liang

    2014-04-01

    Macroporous carbon (MPC) with high pore accessibility and electrical conductivity is of great interest to the electrochemical platform. The development of a simple and efficient route for the direct synthesis of dendritic platinum nanoparticle (DPN) decorated MPC (DPN/MPC) is an interesting challenge, which is highly valuable for electrocatalytic applications. In this study, we propose a very simple route for the one-step synthesis of DPN/MPC in aqueous solution at room temperature without the need for any kind of seed and surfactant to direct the dendritic growth of Pt nanoparticles, which is performed by simply mixing an aqueous solution of K2PtCl4 with MPC and formic acid. The as-prepared DPN/MPC shows high electrocatalytic activities toward the oxidation of methanol and glucose.

  6. Pathological Consequence of Misguided Dendritic Cell Differentiation in Histiocytic Diseases

    Berres, Marie-Luise; Allen, Carl E.; Merad, Miriam

    2013-01-01

    Histiocytic disorders represent a group of complex pathologies characterized by the accumulation of histiocytes, an old term for tissue-resident macrophages and dendritic cells. Langerhans cell histiocytosis is the most frequent of histiocytosis in humans and has been thought to arise from the abnormal accumulation of epidermal dendritic cells called Langerhans cells. In this chapter, we discuss the origin and differentiation of Langerhans cells and dendritic cells and present accumulated evi...

  7. Murid herpesvirus-4 exploits dendritic cells to infect B cells

    Miguel Gaspar; May, Janet S.; Soumi Sukla; Bruno Frederico; Michael B Gill; Smith, Christopher M.; Belz, Gabrielle T.; Stevenson, Philip G.

    2011-01-01

    Author Summary We detect invading viruses with dendritic cells and eliminate them with lymphocytes. A key interaction is lymphocyte activation by dendritic cells presenting viral antigens. Not all viruses can be eliminated, and some that persist deliberately colonize lymphocytes and dendritic cells, such that parasitism and host defence co-exist within the same sites. Once established, these infections are very hard to eliminate. Therefore to vaccinate against them we must determine how infec...

  8. Nanoparticle-aggregated 3D monocrystalline gold dendritic nanostructures

    In this paper, through a simple and fast electroless metal deposition route, gold dendritic nanostructures are synthesized in aqueous conditions. The gold dendrites with a threefold symmetric characteristic were built up of numerous nanoparticles roughly 5-10 nm in size. The aggregated nanoparticles spontaneously experience a self-assembly process along crystallographic orientations and finally form a monocrystalline dendrite. An oriented attachment mechanism can be used to explain the nanoparticle-aggregated self-assembly process

  9. CTAB-Influenced Electrochemical Dissolution of Silver Dendrites.

    O'Regan, Colm; Zhu, Xi; Zhong, Jun; Anand, Utkarsh; Lu, Jingyu; Su, Haibin; Mirsaidov, Utkur

    2016-04-19

    Dendrite formation on the electrodes of a rechargeable battery during the charge-discharge cycle limits its capacity and application due to short-circuits and potential ignition. However, understanding of the underlying dendrite growth and dissolution mechanisms is limited. Here, the electrochemical growth and dissolution of silver dendrites on platinum electrodes immersed in an aqueous silver nitrate (AgNO3) electrolyte solution was investigated using in situ liquid-cell transmission electron microscopy (TEM). The dissolution of Ag dendrites in an AgNO3 solution with added cetyltrimethylammonium bromide (CTAB) surfactant was compared to the dissolution of Ag dendrites in a pure aqueous AgNO3 solution. Significantly, when CTAB was added, dendrite dissolution proceeded in a step-by-step manner, resulting in nanoparticle formation and transient microgrowth stages due to Ostwald ripening. This resulted in complete dissolution of dendrites and "cleaning" of the cell of any silver metal. This is critical for practical battery applications because "dead" lithium is known to cause short circuits and high-discharge rates. In contrast to this, in a pure aqueous AgNO3 solution, without surfactant, dendrites dissolved incompletely back into solution, leaving behind minute traces of disconnected silver particles. Finally, a mechanism for the CTAB-influenced dissolution of silver dendrites was proposed based on electrical field dependent binding energy of CTA(+) to silver. PMID:27017834

  10. Synaptically evoked dendritic action potentials in rat neocortical pyramidal neurons.

    Schwindt, P C; Crill, W E

    1998-05-01

    In a previous study iontophoresis of glutamate on the apical dendrite of layer 5 pyramidal neurons from rat neocortex was used to identify sites at which dendritic depolarization evoked small, prolonged Ca2+ spikes and/or low-threshold Na+ spikes recorded by an intracellular microelectrode in the soma. These spikes were identified as originating in the dendrite. Here we evoke similar dendritic responses by electrical stimulation of presynaptic elements near the tip of the iontophoretic electrode with the use of a second extracellular electrode. In 9 of 12 recorded cells, electrically evoked excitatory postsynaptic potentials (EPSPs) above a minimum size triggered all-or-none postsynaptic responses similar to those evoked by dendritic glutamate iontophoresis at the same site. Both the synaptically evoked and the iontophoretically evoked depolarizations were abolished reversibly by blockade of glutamate receptors. In all recorded cells, the combination of iontophoresis and an EPSP, each of which was subthreshold for the dendritic spike when given alone, evoked a dendritic spike similar to that evoked by a sufficiently large iontophoresis. In one cell tested, dendritic spikes could be evoked by the summation of two independent subthreshold EPSPs evoked by stimulation at two different locations. We conclude that the dendritic spikes are not unique to the use of glutamate iontophoresis because similar spikes can be evoked by EPSPs. We discuss the implications of these results for synaptic integration and for the interpretation of recorded synaptic potentials. PMID:9582218

  11. ω-3 Polyunsaturated fatty acids prevent pressure overload-induced ventricular dilation and decrease in mitochondrial enzymes despite no change in adiponectin

    O'Shea Karen M

    2010-09-01

    Full Text Available Abstract Background Pathological left ventricular (LV hypertrophy frequently progresses to dilated heart failure with suppressed mitochondrial oxidative capacity. Dietary marine ω-3 polyunsaturated fatty acids (ω-3 PUFA up-regulate adiponectin and prevent LV dilation in rats subjected to pressure overload. This study 1 assessed the effects of ω-3 PUFA on LV dilation and down-regulation of mitochondrial enzymes in response to pressure overload; and 2 evaluated the role of adiponectin in mediating the effects of ω-3 PUFA in heart. Methods Wild type (WT and adiponectin-/- mice underwent transverse aortic constriction (TAC and were fed standard chow ± ω-3 PUFA for 6 weeks. At 6 weeks, echocardiography was performed to assess LV function, mice were terminated, and mitochondrial enzyme activities were evaluated. Results TAC induced similar pathological LV hypertrophy compared to sham mice in both strains on both diets. In WT mice TAC increased LV systolic and diastolic volumes and reduced mitochondrial enzyme activities, which were attenuated by ω-3 PUFA without increasing adiponectin. In contrast, adiponectin-/- mice displayed no increase in LV end diastolic and systolic volumes or decrease in mitochondrial enzymes with TAC, and did not respond to ω-3 PUFA. Conclusion These findings suggest ω-3 PUFA attenuates cardiac pathology in response to pressure overload independent of an elevation in adiponectin.

  12. Effect of carbodiimide-derivatized hyaluronic acid gelatin on preventing postsurgical intra-abdominal adhesion formation and promoting healing in a rat model.

    Yuan, Fang; Lin, Long-Xiang; Zhang, Hui-Hui; Huang, Dan; Sun, Yu-Long

    2016-05-01

    Adhesions often occur after abdominal surgery. It could cause chronic pelvic pain, intestinal obstruction, and infertility. A hydrogel biomaterial, carbodiimide-derivatized hyaluronic acid gelatin (cd-HA gelatin), has been successfully used to reduce adhesion formation after flexor tendon grafting. This study investigated the efficacy of cd-HA gelatin in preventing postsurgical peritoneal adhesions in a rat model. The surgical traumas were created on the underlying muscle of the abdominal wall and the serosal layer of the cecum. The wounds were covered with or without cd-HA gelatin. Animals were euthanized at day 14 after surgery. Adhesion formation was assessed with adhesion degree and adhesion breaking strength. The healing of abdominal wall was evaluated with biomechanical testing and histological analysis. The adhesions occurred in all rats (n = 12) without cd-HA gelatin treatment. The application of cd-HA gelatin significantly reduced the adhesion rate from 100% to 58%. The decrease of adhesion breaking strength also manifested that cd-HA gelatin could reduce postsurgical intra-abdominal adhesion formation. Moreover, it was found that cd-HA gelatin was a safe material and could promote tissue healing. The cd-HA gelatin hydrogel could reduce the formation of intra-abdominal adhesions without adversely effects on wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1175-1181, 2016. PMID:26749008

  13. Biocompatible cephalosporin-hydroxyapatite-poly(lactic-co-glycolic acid)-coatings fabricated by MAPLE technique for the prevention of bone implant associated infections

    Rădulescu, Dragoş; Grumezescu, Valentina; Andronescu, Ecaterina; Holban, Alina Maria; Grumezescu, Alexandru Mihai; Socol, Gabriel; Oprea, Alexandra Elena; Rădulescu, Marius; Surdu, Adrian; Trusca, Roxana; Rădulescu, Radu; Chifiriuc, Mariana Carmen; Stan, Miruna S.; Constanda, Sabrina; Dinischiotu, Anca

    2016-06-01

    In this study we aimed to obtain functionalized thin films based on hydroxyapatite/poly(lactic-co-glycolic acid) (HAp/PLGA) containing ceftriaxone/cefuroxime antibiotics (ATBs) deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The prepared thin films were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-Ray diffraction (XRD), selected area electron diffraction (SAED), and infra red (IR) analysis. HAp/PLGA/ATBs thin films sustained the growth of human osteoblasts, proving their good biocompatibility. The microscopic evaluation and the culture-based quantitative assay of the E. coli biofilm development showed that the thin films inhibited the initial step of microbial attachment as well as the subsequent colonization and biofilm development on the respective surfaces. This study demonstrates that MAPLE technique could represent an appealing technique for the fabrication of antibiotics-containing polymeric implant coatings. The bioevaluation results recommend this type of surfaces for the prevention of bone implant microbial contamination and for the enhanced stimulation of the implant osseointegration process.

  14. Fatty acids as natural uncouplers preventing generation of O2.- and H2O2 by mitochondria in the resting state.

    Korshunov, S S; Korkina, O V; Ruuge, E K; Skulachev, V P; Starkov, A A

    1998-09-18

    Both natural (laurate) and artificial (m-chlorocarbonylcyanide phenylhydrazone; CCCP) uncouplers strongly inhibit O2.- and H2O2 formation by rat heart mitochondria oxidizing succinate. Carboxyatractylate, an ATP/ADP antiporter inhibitor, abolishes the laurate inhibition, the CCCP inhibition being unaffected. Atractylate partially releases the inhibition by laurate and decelerates the releasing effect of carboxyatractylate. GDP is much less effective than carboxyatractylate in releasing the laurate inhibition of reactive oxygen species (ROS) formation. Micromolar laurate concentrations arresting the ROS formation cause strong inhibition of reverse electron transfer from succinate to NAD+, whereas State 4 respiration and the transmembrane electric potential difference (delta psi) level are affected only slightly. It is suggested that (i) free fatty acids operate as natural 'mild uncouplers' preventing the transmembrane electrochemical H+ potential difference (delta muH+) from being above a threshold critical for ROS formation by complex I and, to a lesser degree, by complex III of the respiratory chain, and (ii) it is the ATP/ADP-antiporter, rather than uncoupling protein 2, that is mainly involved in this antioxidant mechanism of heart muscle mitochondria. PMID:9762912

  15. Semi-solid Forming of a Damper Housing with Dendritic and Non-dendritic Al-Si-Mg Alloy

    ChenCM; YangCC; ChaoCG

    2001-01-01

    A motorcycle component of damper housing was made by semi-solid forming process. This was used to investigate the effect of microstructures of feedstock on the formability of semisolid process. The soundness and microstructures of casting parts made by dendritic and non-dendritic feedstock were investigated. Separating of liquid phase was found in the casting produced by dendritic feedstock, which might result in defects of porosity, while uniform microstructures were found in the casting produced by no...

  16. Electrochemical performance of dendrite LaFeO3 nanostructures for high selective determination of neurotransmitter compound

    LaFeO3 dendritic nanostructure was synthesized by a well controlled CTAB assisted facile hydrothermal process. The crystal structure, morphology and chemical composition of the material was investigated by X-ray diffraction, high resolution transmission electron microscopy and X-ray photoelectron spectroscopy. Structural characterizations imply the preferential growth along (121) direction by oriented attachment of LaFeO3 nanoparticles in the diffusion limit leading to the formation of LaFeO3 dendrites. The microscopic studies confirm the formation of dendrites with 3-4 μm length, branch diameter 80 nm and length 1-1.5 μm. Further, the electrochemical measurements performed on LaFeO3 dendritic nanostructures deposited on the surface of glassy carbon electrode exhibits strong promoting effect. The oxidation current is proportional to concentration in the linear range 8.2 x 10-8 to 1.6 x 10-7 M with a detection limit of 62 nM with S/N = 3. Meanwhile, the sensor effectively avoids the interference of ascorbic acid and uric acid and it is successfully applied to determine the dopamine formulations with high selectivity and sensitivity. (author)

  17. Ternary eutectic dendrites: Pattern formation and scaling properties

    Rátkai, László; Szállás, Attila; Pusztai, Tamás [Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, P.O. Box 49, H-1525 Budapest (Hungary); Mohri, Tetsuo [Center for Computational Materials Science, Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Gránásy, László, E-mail: granasy.laszlo@wigner.mta.hu [Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, P.O. Box 49, H-1525 Budapest (Hungary); Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom)

    2015-04-21

    Extending previous work [Pusztai et al., Phys. Rev. E 87, 032401 (2013)], we have studied the formation of eutectic dendrites in a model ternary system within the framework of the phase-field theory. We have mapped out the domain in which two-phase dendritic structures grow. With increasing pulling velocity, the following sequence of growth morphologies is observed: flat front lamellae → eutectic colonies → eutectic dendritesdendrites with target pattern → partitionless dendrites → partitionless flat front. We confirm that the two-phase and one-phase dendrites have similar forms and display a similar scaling of the dendrite tip radius with the interface free energy. It is also found that the possible eutectic patterns include the target pattern, and single- and multiarm spirals, of which the thermal fluctuations choose. The most probable number of spiral arms increases with increasing tip radius and with decreasing kinetic anisotropy. Our numerical simulations confirm that in agreement with the assumptions of a recent analysis of two-phase dendrites [Akamatsu et al., Phys. Rev. Lett. 112, 105502 (2014)], the Jackson-Hunt scaling of the eutectic wavelength with pulling velocity is obeyed in the parameter domain explored, and that the natural eutectic wavelength is proportional to the tip radius of the two-phase dendrites. Finally, we find that it is very difficult/virtually impossible to form spiraling two-phase dendrites without anisotropy, an observation that seems to contradict the expectations of Akamatsu et al. Yet, it cannot be excluded that in isotropic systems, two-phase dendrites are rare events difficult to observe in simulations.

  18. Ternary eutectic dendrites: Pattern formation and scaling properties

    Extending previous work [Pusztai et al., Phys. Rev. E 87, 032401 (2013)], we have studied the formation of eutectic dendrites in a model ternary system within the framework of the phase-field theory. We have mapped out the domain in which two-phase dendritic structures grow. With increasing pulling velocity, the following sequence of growth morphologies is observed: flat front lamellae → eutectic colonies → eutectic dendritesdendrites with target pattern → partitionless dendrites → partitionless flat front. We confirm that the two-phase and one-phase dendrites have similar forms and display a similar scaling of the dendrite tip radius with the interface free energy. It is also found that the possible eutectic patterns include the target pattern, and single- and multiarm spirals, of which the thermal fluctuations choose. The most probable number of spiral arms increases with increasing tip radius and with decreasing kinetic anisotropy. Our numerical simulations confirm that in agreement with the assumptions of a recent analysis of two-phase dendrites [Akamatsu et al., Phys. Rev. Lett. 112, 105502 (2014)], the Jackson-Hunt scaling of the eutectic wavelength with pulling velocity is obeyed in the parameter domain explored, and that the natural eutectic wavelength is proportional to the tip radius of the two-phase dendrites. Finally, we find that it is very difficult/virtually impossible to form spiraling two-phase dendrites without anisotropy, an observation that seems to contradict the expectations of Akamatsu et al. Yet, it cannot be excluded that in isotropic systems, two-phase dendrites are rare events difficult to observe in simulations

  19. Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

    Joris D. Veltman

    2010-01-01

    Full Text Available Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.

  20. Intracellular overexpression of HIV-1 Nef impairs differentiation and maturation of monocytic precursors towards dendritic cells.

    Yan Guo

    Full Text Available Nef functions as an immunosuppressive factor critical for HIV-1 replication, survival and development of AIDS following HIV-1 infection. What effects Nef exerts on differentiation and maturation of monocytes towards dendritic cells (DCs remains greatly controversial. In this study, we used THP-1 (human monocytic leukemia cell line as monocytic DC precursors to investigate how overexpression of HIV-1 Nef influences the processes of differentiation and maturation of dendritic cells. In striking contrast to negative controls, our results showed that morphological and phenotypical changes (CD11c, CD14, CD40, CD80, CD83, CD86, and HLA-DR occurred on recombinant THP-1 expressing HIV-1 Nef (short for Nef upon co-stimulation of GM-CSF/IL-4 or GM-CSF/IL-4/TNF-α/ionomycin. Moreover, CD4, CCR5, and CXCR4 were also down-regulated on Nef. It might be hypothesized that Nef prevents superinfection and signal transduction in HIV-1 infected monocytes. Collectively, our study demonstrates that long-lasting expression of Nef at high levels indeed retards differentiation and maturation of dendritic cells in terms of phenotype and morphology. We are hopeful that potentially, stable expression of intracellular Nef in vivo may function as a subtle mode to support long-lasting HIV-1 existence.

  1. Facile synthesis of Ag dendrites on Al foil via galvanic replacement reaction with [Ag(NH3)2]Cl for ultrasensitive SERS detecting of biomolecules

    Symmetric silver dendrites have been synthesized on commercial aluminum foil via galvanic replacement reaction with [Ag(NH3)2]Cl. This process is facile and environmentally friendly, without the use of any templates, surfactants or oxidants, and also avoiding the introduction of fluoride anions as a strong toxicity resulting in hypocalcemia. The products were characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM) and X-ray diffraction (XRD). SEM characterizations and electrochemical measurements including an electrochemical direct current polarization method and OCP-t technique demonstrate that chloride has proven to be the key factor to the formation of well-defined dendritic shape. The as-prepared Ag dendrites are developed as a surface-enhanced Raman scattering (SERS)-active platform for detection of folic acid, DNA and RNA with well resolved bands and high Raman intensities. The detection concentration for the three biomolecules reaches the level of 10−12 M, and thus the symmetric silver dendrites can potentially be employed as effective SERS sensors for label-free and ultrasensitive biomolecule detection. - Highlights: • Simple galvanic replacement is used to synthesize Ag dendrites on commercial Al foils. • This method avoids the introduction of fluoride anions. • The as-prepared dendrites exhibit high SERS activities for biomolecules. • The detection concentration for the biomolecules reaches the level of 10−12 M

  2. CTLA-4 blockade during dendritic cell based booster vaccination influences dendritic cell survival and CTL expansion

    Pedersen, Anders E; Ronchese, Franca

    2007-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells and critical for the priming of CD8+ T cells. Therefore the use of these cells as adjuvant cells has been tested in a large number of experimental and clinical vaccination studies, in particular cancer vaccine studies. A number of protocols...

  3. Dendritic cells modified by vitamin D

    Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg; Zocca, Mai-Britt

    2011-01-01

    Dendritic cells (DCs), the most potent antigen-presenting cells of the immune system, express nuclear receptors for 1,25-dihydroxyvitamin D(3) (VD3) and they are one of its main targets. In the presence of VD3, DCs differentiate into a phenotype that resembles semimature DCs, with reduced T cell...... costimulatory molecules and hampered IL-12 production. These VD3-modulated DCs induce T cell tolerance in vitro using multiple mechanisms such as rendering T cells anergic, dampening of Th1 responses, and recruiting and differentiating regulatory T cells. Due to their ability to specifically target pathological...

  4. Buoyancy effects of a growing, isolated dendrite

    Canright, D.; Davis, S. H.

    1991-01-01

    The buoyancy effect of a growing isolated dendrite on the solidification process in the undercooling liquid material was investigated by developing an analytic solution to the growth/convection problem in powers of a buoyancy parameter G. The solution depends on the Prandtl number P and the Stefan number S (undercooling) for the local velocity and thermal fields and also the buoyant alteration of the interface shape. Results suggest that buoyancy effect for metals (low P) may be qualitatively different from that for organics (high P).

  5. Plasticity of dendritic spines: subcompartmentalization of signaling.

    Colgan, Lesley A; Yasuda, Ryohei

    2014-01-01

    The ability to induce and study neuronal plasticity in single dendritic spines has greatly advanced our understanding of the signaling mechanisms that mediate long-term potentiation. It is now clear that in addition to compartmentalization by the individual spine, subcompartmentalization of biochemical signals occurs at specialized microdomains within the spine. The spatiotemporal coordination of these complex cascades allows for the concomitant remodeling of the postsynaptic density and actin spinoskeleton and for the regulation of membrane traffic to express functional and structural plasticity. Here, we highlight recent findings in the signaling cascades at spine microdomains as well as the challenges and approaches to studying plasticity at the spine level. PMID:24215443

  6. Gliadin fragments promote migration of dendritic cells

    Chládková, Barbara; Kamanová, Jana; Palová-Jelínková, Lenka; Cinová, Jana; Šebo, Peter; Tučková, Ludmila

    2011-01-01

    Roč. 15, č. 4 (2011), 938-948. ISSN 1582-1838 R&D Projects: GA ČR GA310/07/0414; GA ČR GD310/08/H077; GA ČR GA310/08/0447; GA AV ČR IAA500200801; GA AV ČR IAA500200914 Institutional research plan: CEZ:AV0Z50200510 Keywords : celiac disease * gliadin * dendritic cell Subject RIV: EC - Immunology Impact factor: 4.125, year: 2011

  7. Organization of TNIK in dendritic spines.

    Burette, Alain C; Phend, Kristen D; Burette, Susan; Lin, Qingcong; Liang, Musen; Foltz, Gretchen; Taylor, Noël; Wang, Qi; Brandon, Nicholas J; Bates, Brian; Ehlers, Michael D; Weinberg, Richard J

    2015-09-01

    Tumor necrosis factor receptor-associated factor 2 (TRAF2)- and noncatalytic region of tyrosine kinase (NCK)-interacting kinase (TNIK) has been identified as an interactor in the psychiatric risk factor, Disrupted in Schizophrenia 1 (DISC1). As a step toward deciphering its function in the brain, we performed high-resolution light and electron microscopic immunocytochemistry. We demonstrate here that TNIK is expressed in neurons throughout the adult mouse brain. In striatum and cerebral cortex, TNIK concentrates in dendritic spines, especially in the vicinity of the lateral edge of the synapse. Thus, TNIK is highly enriched at a microdomain critical for glutamatergic signaling. PMID:25753355

  8. Metamaterial absorber with random dendritic cells

    Zhu, Weiren; Zhao, Xiaopeng

    2010-05-01

    The metamaterial absorber composed of random dendritic cells has been investigated at microwave frequencies. It is found that the absorptivities come to be weaker and the resonant frequency get red shift as the disordered states increasing, however, the random metamaterial absorber still presents high absorptivity more than 95%. The disordered structures can help understanding of the metamaterial absorber and may be employed for practical design of infrared metamaterial absorber, which may play important roles in collection of radiative heat energy and directional transfer enhancement.

  9. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8+ and CD4+ T cells; the in vitro loading of DCs with tumor antigens

  10. HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells

    Van den Bergh, Johan M J; Guerti, Khadija; Willemen, Yannick; Lion, Eva; Cools, Nathalie; Goossens, Herman; Vorsters, Alex; Van Tendeloo, Viggo F.I.; Anguille, Sébastien; Van Damme, Pierre; Smits, Evelien L. J. M.

    2014-01-01

    Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposur...

  11. Lithium-coated polymeric matrix as a minimum volume-change and dendrite-free lithium metal anode

    Liu, Yayuan; Lin, Dingchang; Liang, Zheng; Zhao, Jie; Yan, Kai; Cui, Yi

    2016-01-01

    Lithium metal is the ideal anode for the next generation of high-energy-density batteries. Nevertheless, dendrite growth, side reactions and infinite relative volume change have prevented it from practical applications. Here, we demonstrate a promising metallic lithium anode design by infusing molten lithium into a polymeric matrix. The electrospun polyimide employed is stable against highly reactive molten lithium and, via a conformal layer of zinc oxide coating to render the surface lithiop...

  12. Subgroup J avian leukosis virus infection of chicken dendritic cells induces apoptosis via the aberrant expression of microRNAs

    Di Liu; Manman Dai; Xu Zhang; Weisheng Cao; Ming Liao

    2016-01-01

    Subgroup J avian leukosis virus (ALV-J) is an oncogenic retrovirus that causes immunosuppression and enhances susceptibility to secondary infection. The innate immune system is the first line of defense in preventing bacterial and viral infections, and dendritic cells (DCs) play important roles in innate immunity. Because bone marrow is an organ that is susceptible to ALV-J, the virus may influence the generation of bone marrow-derived DCs. In this study, DCs cultured in vitro were used to in...

  13. The Mechanisms of Human Renal Epithelial Cell Modulation of Autologous Dendritic Cell Phenotype and Function.

    Sandeep Sampangi

    Full Text Available Proximal tubule epithelial cells (PTEC of the kidney line the proximal tubule downstream of the glomerulus and play a major role in the re-absorption of small molecular weight proteins that may pass through the glomerular filtration process. In the perturbed disease state PTEC also contribute to the inflammatory disease process via both positive and negative mechanisms via the production of inflammatory cytokines which chemo-attract leukocytes and the subsequent down-modulation of these cells to prevent uncontrolled inflammatory responses. It is well established that dendritic cells are responsible for the initiation and direction of adaptive immune responses. Both resident and infiltrating dendritic cells are localised within the tubulointerstitium of the renal cortex, in close apposition to PTEC, in inflammatory disease states. We previously demonstrated that inflammatory PTEC are able to modulate autologous human dendritic cell phenotype and functional responses. Here we extend these findings to characterise the mechanisms of this PTEC immune-modulation using primary human PTEC and autologous monocyte-derived dendritic cells (MoDC as the model system. We demonstrate that PTEC express three inhibitory molecules: (i cell surface PD-L1 that induces MoDC expression of PD-L1; (ii intracellular IDO that maintains the expression of MoDC CD14, drives the expression of CD80, PD-L1 and IL-10 by MoDC and inhibits T cell stimulatory capacity; and (iii soluble HLA-G (sHLA-G that inhibits HLA-DR and induces IL-10 expression by MoDC. Collectively the results demonstrate that primary human PTEC are able to modulate autologous DC phenotype and function via multiple complex pathways. Further dissection of these pathways is essential to target therapeutic strategies in the treatment of inflammatory kidney disorders.

  14. Measles Virus Induces Functional TRAIL Production by Human Dendritic Cells

    Vidalain, Pierre-Olivier; Azocar, Olga; Lamouille, Barbara; Astier, Anne; Rabourdin-Combe, Chantal; Servet-Delprat, Christine

    2000-01-01

    Measles virus infection induces a profound immunosuppression that can lead to serious secondary infections. Here we demonstrate that measles virus induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA and protein expression in human monocyte-derived dendritic cells. Moreover, measles virus-infected dendritic cells are shown to be cytotoxic via the TRAIL pathway. PMID:10590149

  15. Measles Virus Induces Functional TRAIL Production by Human Dendritic Cells

    Vidalain, Pierre-Olivier; Azocar, Olga; Lamouille, Barbara; Astier, Anne; Rabourdin-Combe, Chantal; Servet-Delprat, Christine

    2000-01-01

    Measles virus infection induces a profound immunosuppression that can lead to serious secondary infections. Here we demonstrate that measles virus induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA and protein expression in human monocyte-derived dendritic cells. Moreover, measles virus-infected dendritic cells are shown to be cytotoxic via the TRAIL pathway.

  16. Dendritic Spines in Depression: What We Learned from Animal Models

    Hui Qiao; Ming-Xing Li; Chang Xu; Hui-Bin Chen; Shu-Cheng An; Xin-Ming Ma

    2016-01-01

    Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have ...

  17. Contribution of sublinear and supralinear dendritic integration to neuronal computations

    Alexandra eTran-Van-Minh

    2015-03-01

    Full Text Available Nonlinear dendritic integration is thought to increase the computational ability of neurons. Most studies focus on how supralinear summation of excitatory synaptic responses arising from clustered inputs within single dendrites result in the enhancement of neuronal firing, enabling simple computations such as feature detection. Recent reports have shown that sublinear summation is also a prominent dendritic operation, extending the range of subthreshold input-output transformations conferred by dendrites. Like supralinear operations, sublinear dendritic operations also increase the repertoire of neuronal computations, but feature extraction requires different synaptic connectivity strategies for each of these operations. In this article we will review the experimental and theoretical findings describing the biophysical determinants of the three primary classes of dendritic operations: linear, sublinear, and supralinear. We then review a Boolean algebra-based analysis of simplified neuron models, which provides insight into how dendritic operations influence neuronal computations. We highlight how neuronal computations are critically dependent on the interplay of dendritic properties (morphology and voltage-gated channel expression, spiking threshold and distribution of synaptic inputs carrying particular sensory features. Finally, we describe how global (scattered and local (clustered integration strategies permit the implementation of similar classes of computations, one example being the object feature binding problem.

  18. The VITamin D and OmegA-3 TriaL (VITAL): Rationale and Design of a Large Randomized Controlled Trial of Vitamin D and Marine Omega-3 Fatty Acid Supplements for the Primary Prevention of Cancer and Cardiovascular Disease

    Manson, JoAnn E.; Bassuk, Shari S.; Lee, I-Min; Cook, Nancy R.; Albert, Michelle A.; Gordon, David; Zaharris, Elaine; MacFadyen, Jean G.; Danielson, Eleanor; Lin, Jennifer; Zhang, Shumin M.; Buring, Julie E

    2011-01-01

    Data from laboratory studies, observational research, and/or secondary prevention trials suggest that vitamin D and marine omega-3 fatty acids may reduce risk for cancer or cardiovascular disease (CVD), but primary prevention trials with adequate dosing in general populations (i.e., unselected for disease risk) are lacking. The ongoing VITamin D and OmegA-3 TriaL (VITAL) is a large randomized, double-blind, placebo-controlled, 2×2 factorial trial of vitamin D (in the form of vitamin D3 [chole...

  19. On/off TLR segnaling decides immunogenic or tolerogenic dendritic cell maturation upon NKT cell contact

    Caielli,

    2009-01-01

    Invariant Natural Killer (iNK)T cells play opposite immune functions. They participate in the innate immune response to promote anti-microbial and anti-tumor immunity and they are crucial to maintain T cell tolerance and prevent autoimmune diseases. While it is well known that the adjuvant function of iNKT cells is mediated through maturation of dendritic cells (DC), the mechanism underlying the tolerogenic function of iNKT cells remains unclear. We performed co-culture experiments with immat...

  20. Evidence for rapid inter- and intramolecular chlorine transfer reactions of histamine and carnosine chloramines: implications for the prevention of hypochlorous-acid-mediated damage.

    Pattison, David I; Davies, Michael J

    2006-07-01

    Hypochlorous acid (HOCl) is a powerful oxidant generated from H(2)O(2) and Cl(-) by the heme enzyme myeloperoxidase, which is released from activated leukocytes. HOCl possesses potent antibacterial properties, but excessive production can lead to host tissue damage that is implicated in a wide range of human diseases (e.g., atherosclerosis). Histamine and carnosine have been proposed as protective agents against such damage. However, as recent studies have shown that histidine-containing compounds readily form imidazole chloramines that can rapidly chlorinate other targets, it was hypothesized that similar reactions may occur with histamine and carnosine, leading to propagation, rather than prevention, of HOCl-mediated damage. In this study, the reactions of HOCl with histamine, histidine, carnosine, and other compounds containing imidazole and free amine sites were examined. In all cases, rapid formation (k, 1.6 x 10(5) M(-)(1) s(-)(1)) of imidazole chloramines was observed, followed by chlorine transfer to yield more stable, primary chloramines (R-NHCl). The rates of most of these secondary reactions are dependent upon substrate concentrations, consistent with intermolecular mechanisms (k, 10(3)-10(4) M(-)(1) s(-)(1)). However, for carnosine, the imidazole chloramine transfer rates are independent of the concentration, indicative of intramolecular processes (k, 0.6 s(-)(1)). High-performance liquid chromatography studies show that in all cases the resultant R-NHCl species can slowly chlorinate N-alpha-acetyl-Tyr. Thus, the current data indicate that the chloramines formed on the imidazole and free amine groups of these compounds can oxidize other target molecules but with limited efficiency, suggesting that histamine and particularly carnosine may be able to limit HOCl-mediated oxidation in vivo. PMID:16800640

  1. Immune Monitoring Using mRNA-Transfected Dendritic Cells.

    Borch, Troels Holz; Svane, Inge Marie; Met, Özcan

    2016-01-01

    Dendritic cells are known to be the most potent antigen presenting cell in the immune system and are used as cellular adjuvants in therapeutic anticancer vaccines using various tumor-associated antigens or their derivatives. One way of loading antigen into the dendritic cells is by mRNA electroporation, ensuring presentation of antigen through major histocompatibility complex I and potentially activating T cells, enabling them to kill the tumor cells. Despite extensive research in the field, only one dendritic cell-based vaccine has been approved. There is therefore a great need to elucidate and understand the immunological impact of dendritic cell vaccination in order to improve clinical benefit. In this chapter, we describe a method for performing immune monitoring using peripheral blood mononuclear cells and autologous dendritic cells transfected with tumor-associated antigen-encoding mRNA. PMID:27236804

  2. Synthesis and field emission properties of Cu dendritic nanostructures

    Xu, Jianwen; Yu, Ke; Zhu, Ziqiang

    2010-03-01

    Cu dendritic nanostructures were synthesized on ITO glass substructure by electrochemical deposition. SEM images showed that these Cu dendritic nanostuctures revealed a clear and well-defined dendritic fractal structure with a pronounced trunk and highly ordered branches distributed on both sides of the trunk. The diffusion-limited aggregation (DLA) model was used to explain the fractal growth of Cu dendritic nanostructures. Field emission properties of these Cu dendritic nanostructures were measured, which have possessed good performance with the turn-on field of 7.5 V/μm (defined as the electric field required to be detected at a current density of 0.1 mA/cm 2) and the field enhancement factor β of 1094.

  3. Dendrite coherency of Al-Si-Cu alloys

    Veldman, Natalia L. M.; Dahle, Arne K.; Stjohn, David H.; Arnberg, Lars

    2001-01-01

    The dendrite coherency point of Al-Si-Cu alloys was determined by thermal analysis and rheological measurement methods by performing parallel measurements at two cooling rates for aluminum alloys across a wide range of silicon and copper contents. Contrary to previous findings, the two methods yield significantly different values for the fraction solid at the dendrite coherency point. This disparity is greatest for alloys of low solute concentration. The results from this study also contradict previously reported trends in the effect of cooling rate on the dendritic coherency point. Consideration of the results shows that thermal analysis is not a valid technique for the measurement of coherency. Analysis of the results from rheological testing indicates that silicon concentration has a dominant effect on grain size and dendritic morphology, independent of cooling rate and copper content, and thus is the factor that determines the fraction solid at dendrite coherency for Al-Si-Cu alloys.

  4. Regulation of Dendritic Cell Function by Dietary Polyphenols.

    Del Cornò, Manuela; Scazzocchio, Beatrice; Masella, Roberta; Gessani, Sandra

    2016-04-01

    Marked changes in socioeconomic status, cultural traditions, population growth, and agriculture have been affecting diets worldwide. Nutrition is known to play a pivotal role in the pathogenesis of several chronic diseases, and the use of bioactive food compounds at pharmacologic doses is emerging as a preventive and/or therapeutic approach to target metabolic dysregulations occurring in aging, obesity-related chronic diseases, and cancer. Only recently have data on the effects of specific nutrients or food on the immune system become available, and studies regarding the human immune system are still in their infancy. Beyond providing essential nutrients, diet can actively influence the immune system. Understanding how diet and nutritional status influence the innate and adaptive arms of our immune system represents an area of scientific need, opportunity, and challenge. The insights gleaned should help to address several pressing global health problems. Recently, biologically active polyphenols, which are widespread constituents of fruit and vegetables, have gained importance as complex regulators of various cellular processes, critically involved in the maintenance of body homeostasis. This review outlines the potential effects of polyphenols on the function of dendritic cells (DCs), key players in the orchestration of the immune response. Their effects on different aspects of DC biology including differentiation, maturation, and DC capacity to shift immune response toward tolerance or immune activation will be outlined. PMID:24941314

  5. Simian immunodeficiency virus interactions with macaque dendritic cells.

    Teleshova, Natalia; Derby, Nina; Martinelli, Elena; Pugach, Pavel; Calenda, Giulia; Robbiani, Melissa

    2013-01-01

    This chapter summarizes advances in the following areas: (1) dendritic cell (DC)-mediated simian immunodeficiency virus (SIV) transmission, (2) role of DCs in innate and adaptive immunity against SIV, and (3) approaches to harness DC function to induce anti-SIV responses. The nonhuman primate (NHP) model of human immunodeficiency virus (HIV) infection in rhesus macaques and other Asian NHP species is highly relevant to advance the understanding of virus-host interactions critical for transmission and disease pathogenesis. HIV infection is associated with changes in frequency, phenotype, and function of the two principal subsets of DCs, myeloid DCs and plasmacytoid DCs. DC biology during pathogenic SIV infection is strikingly similar to that observed in HIV-infected patients. The NHP models provide an opportunity to dissect the requirements for DC-driven SIV infection and to understand how SIV distorts the DC system to its advantage. Furthermore, the SIV model of mucosal transmission enables the study of the earliest events of infection at the portal of entry that cannot be studied in humans, and, importantly, the involvement of DCs. Nonpathogenic infection in African NHP hosts allows investigations into the role of DCs in disease control. Understanding how DCs are altered during SIV infection is critical to the design of therapeutic and preventative strategies against HIV. PMID:22975875

  6. Comparison of murine hepatic accessory cells and splenic dendritic cells

    Accessory cells are required for proliferation and antibody synthesis of B lymphocytes and proliferation of T lymphocytes in primary immune responses in vitro. The obligatory cells derived from the spleen are referred to as dendritic cells. Accessory cells were isolated from normal adult livers which were functionally interchangeable with splenic DC. Both hepatic accessory cells (AC) and splenic DC adhere firmly to plastic culture dishes or wells within 2 hr; but hepatic AC, unlike splenic DC, do not detach during 22 hr additional incubation. Hepatic AC, unlike splenic DC, are not lysed or inactivated by monoclonal antibody 33D1 and C'. Hepatic AC and splenic DC are similarly sensitive to irradiation in vivo and insensitive to irradiation in vitro. Hepatic AC are separated with cells which are predominantly phagocytic and FcR+ and contain nonspecific esterase. Both hepatic AC and splenic DC are suppressed or eliminated by activation of NK cells in vivo, a phenomenon prevented by prior elimination of NK cells

  7. Analyzing dendritic growth in a population of immature neurons in the adult dentate gyrus using laminar quantification of disjointed dendrites

    ShiraRosenzweig

    2011-03-01

    Full Text Available In the dentate gyrus of the hippocampus, new granule neurons are continuously produced throughout adult life. A prerequisite for the successful synaptic integration of these neurons is the sprouting and extension of dendrites into the molecular layer of the dentate gyrus. Thus, studies aimed at investigating the developmental stages of adult neurogenesis often use dendritic growth as an important indicator of neuronal health and maturity. Based on the known topography of the dentate gyrus, characterized by distinct laminar arrangement of granule neurons and their extensions, we have developed a new method for analysis of dendritic growth in immature adult-born granule neurons. The method is comprised of laminar quantification of cell bodies, primary, secondary and tertiary dendrites separately and independently from each other. In contrast to most existing methods, laminar quantification of dendrites does not require the use of exogenous markers and does not involve arbitrary selection of individual neurons. The new method relies on immonuhistochemical detection of endogenous markers such as doublecortin to perform a comprehensive analysis of a sub-population of immature neurons. Disjointed, “orphan” dendrites that often appear in the thin histological sections are taken into account. Using several experimental groups of rats and mice, we demonstrate here the suitable techniques for quantifying neurons and dendrites, and explain how the ratios between the quantified values can be used in a comparative analysis to indicate variations in dendritic growth and complexity.

  8. Dendritic Cells in vivo and in vitro

    HuiWan; MarcelDupasquier

    2005-01-01

    Dendritic cells (DC) are crucial cells of the immune system, and bridged the essential connection between innate and adaptive immunity. They reside in the periphery as sentinels where they take up antigens. Upon activation, they migrate to lymphoid organs and present there the processed antigens to T cells, thereby activating them and eliciting a potent immune response. Dendritic cells are bone marrow-derived cells, still big controversies exist about their in vivo development. In vitro, DC can be generated from multiple precursor cells, among them lymphoid and myeloid committed progenitors. Although it remains unknown how DC are generated in vivo, studying the functions of in vitro generated DC results in fundamental knowledge of the DC biology with promising applications for future medicine. Therefore, in this review, we present current protocols for the generation of DC from precursors in vitro. We will do this for the mouse system, where most research occurs and for the human system, where research concentrates on implementing DC biology in disease treatments. Cellular & Molecular Immunology. 2005;2(1):28-35.

  9. Dendritic Cells in vivo and in vitro

    Hui Wan; Marcel Dupasquier

    2005-01-01

    Dendritic cells (DC) are crucial cells of the immune system, and bridged the essential connection between innate and adaptive immunity. They reside in the periphery as sentinels where they take up antigens. Upon activation,they migrate to lymphoid organs and present there the processed antigens to T cells, thereby activating them and eliciting a potent immune response. Dendritic cells are bone marrow-derived cells, still big controversies exist about their in vivo development. In vitro, DC can be generated from multiple precursor cells, among them lymphoid and myeloid committed progenitors. Although it remains unknown how DC are generated in vivo,studying the functions of in vitro generated DC results in fundamental knowledge of the DC biology with promising applications for future medicine. Therefore, in this review, we present current protocols for the generation of DC from precursors in vitro. We will do this for the mouse system, where most research occurs and for the human system, where research concentrates on implementing DC biology in disease treatments.

  10. 3α-6α-Dihydroxy-7α-fluoro-5β-cholanoate (UPF-680), physicochemical and physiological properties of a new fluorinated bile acid that prevents 17α-ethynyl-estradiol-induced cholestasis in rats

    3α-6α-Dihydroxy-7α-fluoro-5β-cholanoate (UPF-680), the 7α-fluorine analog of hyodeoxycholic acid (HDCA), was synthesized to improve bioavailability and stability of ursodeoxycholic acid (UDCA). Acute rat biliary fistula and chronic cholestasis induced by 17α-ethynyl-estradiol (17EE) models were used to study and compare the effects of UPF-680 (dose range 0.6-6.0 μmol/kg min) with UDCA on bile flow, biliary bicarbonate (HCO3-), lipid output, biliary bile acid composition, hepatic enzymes and organic anion pumps. In acute infusion, UPF-680 increased bile flow in a dose-related manner, by up to 40.9%. Biliary HCO3- output was similarly increased. Changes were observed in phospholipid secretion only at the highest doses. Treatment with UDCA and UPF-680 reversed chronic cholestasis induced by 17EE; in this model, UDCA had no effect on bile flow in contrast to UPF-680, which significantly increased bile flow. With acute administration of UPF-680, the biliary bile acid pool became enriched with unconjugated and conjugated UPF-680 (71.7%) at the expense of endogenous cholic acid and muricholic isomers. With chronic administration of UPF-680 or UDCA, the main biliary bile acids were tauro conjugates, but modification of biliary bile acid pool was greater with UPF-680. UPF-680 increased the mRNA for cytochrome P450 7A1 (CYP7A1) and cytochrome P450 8B (CYP8B). Both UDCA and UPF-680 increased the mRNA for Na+ taurocholate co-transporting polypeptide (NCTP). In conclusion, UPF-680 prevented 17EE-induced cholestasis and enriched the biliary bile acid pool with less detergent and cytotoxic bile acids. This novel fluorinated bile acid may have potential in the treatment of cholestatic liver disease

  11. Antenatal iron/folic acid supplements, but not postnatal care, prevents neonatal deaths in Indonesia: analysis of Indonesia Demographic and Health Surveys 2002/2003–2007 (a retrospective cohort study)

    Titaley, Christiana Rialine; Dibley, Michael John

    2012-01-01

    Objective This study aimed to assess the contribution of postnatal services to the risk of neonatal mortality, and the relative contributions of antenatal iron/folic acid supplements and postnatal care in preventing neonatal mortality in Indonesia. Design Retrospective cohort study. Setting and participants Data used in this study were the 2002–2007 Indonesia Demographic and Health Surveys, nationally representative surveys. The pooled data provided survival information of 26 591 most recent ...

  12. Cutting edge: B220+CCR9- dendritic cells are not plasmacytoid dendritic cells but are precursors of conventional dendritic cells.

    Segura, Elodie; Wong, June; Villadangos, José A

    2009-08-01

    Mouse lymphoid organs contain two major subsets of dendritic cells (DC) that differ in their phenotype and functions: conventional DC (cDC) and plasmacytoid DC (pDC). Recently, it has been proposed that differential expression of CCR9 could distinguish functionally distinct pDC subsets. We show that B220(+)CCR9(-) DC do not express classical pDC markers and have a developmental origin different from that of pDC. Furthermore, B220(+)CCR9(-) DC do not secrete IFN-alpha in response to CpG and, unlike pDC, can efficiently present exogenous Ags. Our results demonstrate that B220(+)CCR9(-) DC do not represent a subset of pDC. After in vivo transfer, these cells down-regulate B220 expression and convert into the two major cDC subsets, showing that they are a developmental stage of cDC differentiation. PMID:19570827

  13. CXCR4 engagement promotes dendritic cell survival and maturation

    It has been reported that human monocyte derived-dendritic cells (DCs) express CXCR4, responsible for chemotaxis to CXCL12. However, it remains unknown whether CXCR4 is involved in other functions of DCs. Initially, we found that CXCR4 was expressed on bone marrow-derived DCs (BMDCs). The addition of specific CXCR4 antagonist, 4-F-Benzoyl-TN14003, to the culture of mouse BMDCs decreased their number, especially the mature subset of them. The similar effect was found on the number of Langerhans cells (LCs) but not keratinocytes among epidermal cell suspensions. Since LCs are incapable of proliferating in vitro, these results indicate that CXCR4 engagement is important for not only maturation but also survival of DCs. Consistently, the dinitrobenzene sulfonic acid-induced, antigen-specific in vitro proliferation of previously sensitized lymph node cells was enhanced by CXCL12, and suppressed by CXCR4 antagonist. These findings suggest that CXCL12-CXCR4 engagement enhances DC maturation and survival to initiate acquired immune response

  14. Uptake and intracellular trafficking of superantigens in dendritic cells.

    María B Ganem

    Full Text Available Bacterial superantigens (SAgs are exotoxins produced mainly by Staphylococcus aureus and Streptococcus pyogenes that can cause toxic shock syndrome (TSS. According to current paradigm, SAgs interact directly and simultaneously with T cell receptor (TCR on the T cell and MHC class II (MHC-II on the antigen-presenting cell (APC, thereby circumventing intracellular processing to trigger T cell activation. Dendritic cells (DCs are professional APCs that coat nearly all body surfaces and are the most probable candidate to interact with SAgs. We demonstrate that SAgs are taken up by mouse DCs without triggering DC maturation. SAgs were found in intracellular acidic compartment of DCs as biologically active molecules. Moreover, SAgs co-localized with EEA1, RAB-7 and LAMP-2, at different times, and were then recycled to the cell membrane. DCs loaded with SAgs are capable of triggering in vitro lymphocyte proliferation and, injected into mice, stimulate T cells bearing the proper TCR in draining lymph nodes. Transportation and trafficking of SAgs in DCs might increase the local concentration of these exotoxins where they will produce the highest effect by promoting their encounter with both MHC-II and TCR in lymph nodes, and may explain how just a few SAg molecules can induce the severe pathology associated with TSS.

  15. 5-Lipoxygenase Pathway, Dendritic Cells, and Adaptive Immunity

    Hedi Harizi

    2004-01-01

    Full Text Available 5-lipoxygenase (5-LO pathway is the major source of potent proinflammatory leukotrienes (LTs issued from the metabolism of arachidonic acid (AA, and best known for their roles in the pathogenesis of asthma. These lipid mediators are mainly released from myeloid cells and may act as physiological autocrine and paracrine signalling molecules, and play a central role in regulating the interaction between innate and adaptive immunity. The biological actions of LTs including their immunoregulatory and proinflammatory effects are mediated through extracellular specific G-protein-coupled receptors. Despite their role in inflammatory cells, such as neutrophils and macrophages, LTs may have important effects on dendritic cells (DC-mediated adaptive immunity. Several lines of evidence show that DC not only are important source of LTs, but also become targets of their actions by producing other lipid mediators and proinflammatory molecules. This review focuses on advances in 5-LO pathway biology, the production of LTs from DC and their role on various cells of immune system and in adaptive immunity.

  16. Rapid acquisition of dendritic spines by visual thalamic neurons after blockade of N-methyl-D-aspartate receptors.

    Rocha, M; Sur, M.

    1995-01-01

    N-Methyl-D-aspartate (NMDA) receptors play an important role in the development of retinal axon arbors in the mammalian lateral geniculate nucleus (LGN). We investigated whether blockade of NMDA receptors in vivo or in vitro affects the dendritic development of LGN neurons during the period that retinogeniculate axons segregate into on-center and off-center sublaminae. Osmotic minipumps containing either the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV) or saline were imp...

  17. Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation.

    Zsuzsanna Szepesi

    Full Text Available Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs, a family of extracellularly acting and Zn(2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.

  18. Dendritic solidification morphology viewed from the perspective of constructal theory

    In this paper we focus on the application of the constructal theory in predicting the dendritic solid structure. First we analyse the marginal stability criterion from the perspective of the constructal principle. Having as a guiding principle the constructal law we have shown that among the whole range of possible dendrite tip radiuses predicted by the stability analysis the dendrite tip will choose the smallest one, that is a radius equal with the smallest perturbation wavelength leading to instabilities. We identify as well the existence of a competition between the diffusion controlled growth and the dendritic growth. Second, we develop a model for the secondary arm spacing. We identify a competition between the lateral diffusion controlled growth of a needle and the dendritic growth of lateral secondary arms. By analysing this competition we are able to characterize the sidebranching mechanism and to finally compute the secondary arm spacing. The result is in good agreement with the experimental results. Finally, the primary arm spacing is analysed from the perspective of the constructal law. The constructal law predicts that the only way the columnar tips can optimize the solidification process is to minimize the spacing between two adjacent tips, namely λ1. By quantifying the two mechanisms responsible for the selection of λ1, the dendrite division and the dendrite overgrown mechanisms, we were finally able to obtain a model for the primary arm spacing. This model is also validated against various experimental data

  19. NMDA spike/plateau potentials in dendrites of thalamocortical neurons.

    Augustinaite, Sigita; Kuhn, Bernd; Helm, Paul Johannes; Heggelund, Paul

    2014-08-13

    Dendritic NMDA spike/plateau potentials, first discovered in cortical pyramidal neurons, provide supralinear integration of synaptic inputs on thin and distal dendrites, thereby increasing the impact of these inputs on the soma. The more specific functional role of these potentials has been difficult to clarify, partly due to the complex circuitry of cortical neurons. Thalamocortical (TC) neurons in the dorsal lateral geniculate nucleus participate in simpler circuits. They receive their primary afferent input from retina and send their output to visual cortex. Cortex, in turn, regulates this output through massive feedback to distal dendrites of the TC neurons. The TC neurons can operate in two modes related to behavioral states: burst mode prevailing during sleep, when T-type calcium bursts largely disrupt the transfer of signals from retina to cortex, and tonic mode, which provides reliable transfer of retinal signals to cortex during wakefulness. We studied dendritic potentials in TC neurons with combined two-photon calcium imaging and whole-cell recording of responses to local dendritic glutamate iontophoresis in acute brain slices from mice. We found that NMDA spike/plateaus can be elicited locally at distal dendrites of TC neurons. We suggest that these dendritic potentials have important functions in the cortical regulation of thalamocortical transmission. NMDA spike/plateaus can induce shifts in the functional mode from burst to tonic by blockade of T-type calcium conductances. Moreover, in tonic mode, they can facilitate the transfer of retinal signals to cortex by depolarization of TC neurons. PMID:25122891

  20. Dendritic mitochondria reach stable positions during circuit development

    Faits, Michelle C; Zhang, Chunmeng; Soto, Florentina; Kerschensteiner, Daniel

    2016-01-01

    Mitochondria move throughout neuronal dendrites and localize to sites of energy demand. The prevailing view of dendritic mitochondria as highly motile organelles whose distribution is continually adjusted by neuronal activity via Ca2+-dependent arrests is based on observations in cultured neurons exposed to artificial stimuli. Here, we analyze the movements of mitochondria in ganglion cell dendrites in the intact retina. We find that whereas during development 30% of mitochondria are motile at any time, as dendrites mature, mitochondria all but stop moving and localize stably to synapses and branch points. Neither spontaneous nor sensory-evoked activity and Ca2+ transients alter motility of dendritic mitochondria; and pathological hyperactivity in a mouse model of retinal degeneration elevates rather than reduces motility. Thus, our findings indicate that dendritic mitochondria reach stable positions during a critical developmental period of high motility, and challenge current views about the role of activity in regulating mitochondrial transport in dendrites. DOI: http://dx.doi.org/10.7554/eLife.11583.001 PMID:26742087

  1. Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors

    Lauren M DePoy

    2014-10-01

    Full Text Available Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC. Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31-35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability – the p190rhogap+/- mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/- mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/- mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC, and they suggest that cocaine-induced modifications in dendrite structure may contribute to the behavioral effects of cocaine more so than pre-existing structural abnormalities in this cell population.

  2. Control of dendritic morphogenesis by Trio in Drosophila melanogaster.

    Madhuri Shivalkar

    Full Text Available Abl tyrosine kinase and its effectors among the Rho family of GTPases each act to control dendritic morphogenesis in Drosophila. It has not been established, however, which of the many GTPase regulators in the cell link these signaling molecules in the dendrite. In axons, the bifunctional guanine exchange factor, Trio, is an essential link between the Abl tyrosine kinase signaling pathway and Rho GTPases, particularly Rac, allowing these systems to act coordinately to control actin organization. In dendritic morphogenesis, however, Abl and Rac have contrary rather than reinforcing effects, raising the question of whether Trio is involved, and if so, whether it acts through Rac, Rho or both. We now find that Trio is expressed in sensory neurons of the Drosophila embryo and regulates their dendritic arborization. trio mutants display a reduction in dendritic branching and increase in average branch length, whereas over-expression of trio has the opposite effect. We further show that it is the Rac GEF domain of Trio, and not its Rho GEF domain that is primarily responsible for the dendritic function of Trio. Thus, Trio shapes the complexity of dendritic arbors and does so in a way that mimics the effects of its target, Rac.

  3. Design of tumor-specific immunotherapies using dendritic cells - effect of bromelain on dendritic cell maturation

    Karlsen, Marie

    2009-01-01

    Immunotherapy using dendritic cells (DC) has shown promising results in clinical trials, but few relevant successes are recorded. Therefore, the choice of an appropriate DC population is critical for the outcome of this treatment. The DC used today in immunotherapy are often matured with a cytokine cocktail consisting of TNF-α, IL-1β, IL-6 and PGE2. These cells have deficits in their cytokine production, and also their migratory capacity in vivo needs improvement. After being introduced to br...

  4. Fractal structures of dendrites in GaSe crystals

    Kolesnikov, N. N.; Borisenko, E. B.; Borisenko, D. N.; Bozhko, S. I.

    2008-07-01

    Solidification of melts at substantial supercooling is associated with instability on the growth front. This causes growth of dendrites, which form as a branched tree in a crystal. In the layered melt-grown GaSe crystals dendrites are observed, if growth rates are rather high [N.N. Kolesnikov, E.B. Borisenko, D.N. Borisenko, V.K. Gartman, Influence of growth conditions on microstructure and properties of GaSe crystals, J. Crystal Growth 300 (2) (2007) 294-298]. Models based on solution of the thermal diffusion problem are traditionally used to describe dendrite growth. Solution of this problem requires information about several physical parameters, such as diffusion coefficient, heat conductivity coefficient and supercooling at the solid/liquid interface. The study of scale invariance of dendrites formed in a crystal provides a new approach to solution of the dynamic growth problem. The calculated fractal dimensionality of the experimentally observed dendrites in GaSe crystals is D=1.7. It coincides with dimensionality of the clusters obtained through computer simulation in terms of the model of diffusion-limited aggregation (DLA). This result provides a new approach to description of the dynamics of dendrite growth. We have shown that the dendrite growth mechanism in the layered semiconductor crystals can be described by a two-dimensional DLA model. It is shown that probabilistic simulation can be used to show the development of a dendrite in any material. In contrast to the classical theories of dendrite growth, this approach does not require information on physical parameters.

  5. Rape prevention

    Date rape - prevention; Sexual assault - prevention ... Centers for Disease Control and Prevention (CDC). Sexual assault and STDs. In: Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep . 2010;17(59)(RR-12):90- ...

  6. Information Fusion for Anomaly Detection with the Dendritic Cell Algorithm

    Greensmith, Julie; Tedesco, Gianni

    2010-01-01

    Dendritic cells are antigen presenting cells that provide a vital link between the innate and adaptive immune system, providing the initial detection of pathogenic invaders. Research into this family of cells has revealed that they perform information fusion which directs immune responses. We have derived a Dendritic Cell Algorithm based on the functionality of these cells, by modelling the biological signals and differentiation pathways to build a control mechanism for an artificial immune system. We present algorithmic details in addition to experimental results, when the algorithm was applied to anomaly detection for the detection of port scans. The results show the Dendritic Cell Algorithm is sucessful at detecting port scans.

  7. Follicular Dendritic Cell Sarcoma of the Abdomen: the Imaging Findings

    Kang, Tae Wook; Lee, Soon Jin; Song, Hye Jong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2010-04-15

    Follicular dendritic cell sarcoma is a rare neoplasm that originates from follicular dendritic cells in lymphoid follicles. This disease usually involves the lymph nodes, and especially the head and neck area. Rarely, extranodal sites may be affected, including tonsil, the oral cavity, liver, spleen and the gastrointestinal tract. We report here on the imaging findings of follicular dendritic cell sarcoma of the abdomen that involved the retroperitoneal lymph nodes and colon. It shows as a well-defined, enhancing homogenous mass with internal necrosis and regional lymphadenopathy.

  8. Harnessing dendritic cells in inflammatory skin diseases.

    Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O

    2011-02-01

    The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. PMID:21295490

  9. Isolation of Human Skin Dendritic Cell Subsets.

    Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

    2016-01-01

    Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages. PMID:27142012

  10. Dendritic Cells and Humoral Immunity in Humans

    Ueno, Hideki; Schmitt, Nathalie; Palucka, A. Karolina; Banchereau, Jacques

    2010-01-01

    Summary Dendritic cells (DCs) orchestrate the innate and adaptive immune systems to induce tolerance and immunity. DC plasticity and subsets are prominent determinants in the regulation of immune responses. Our recent studies suggest that humoral and cellular immunity is regulated by different myeloid DC subsets with distinct intrinsic properties in humans. While antibody response is preferentially mediated by CD14+ dermal DCs, cytotoxic T cell response is preferentially mediated by Langerhans cells (LCs). Thus, mechanisms whereby DCs induce humoral and cellular immunity appear to be fundamentally distinct. In this review, we will focus on the role of DCs in the development of humoral immunity. We will also discuss the mechanisms whereby DCs induce CD4+ T cells associated with the help of B cell response, including T follicular helper (Tfh) cells, and why human LCs lack this ability. PMID:20309010

  11. Harnessing Human Dendritic Cell Subsets for Medicine

    Ueno, Hideki; Schmitt, Nathalie; Klechevsky, Eynav; Pedroza-Gonzales, Alexander; Matsui, Toshimichi; Zurawski, Gerard; Oh, SangKon; Fay, Joseph; Pascual, Virginia; Banchereau, Jacques; Palucka, Karolina

    2010-01-01

    Summary Immunity results from a complex interplay between the antigen-nonspecific innate immune system and the antigen-specific adaptive immune system. The cells and molecules of the innate system employ non-clonal recognition receptors including lectins, Toll-like receptors, NOD-like receptors and helicases. B and T lymphocytes of the adaptive immune system employ clonal receptors recognizing antigens or their derived peptides in a highly specific manner. An essential link between innate and adaptive immunity is provided by dendritic cells (DCs). DCs can induce such contrasting states as immunity and tolerance. The recent years have brought a wealth of information on the biology of DCs revealing the complexity of this cell system. Indeed, DC plasticity and subsets are prominent determinants of the type and quality of elicited immune responses. Here we summarize our recent studies aimed at a better understanding of the DC system to unravel the pathophysiology of human diseases and design novel human vaccines. PMID:20193020

  12. Immunotherapy of hematological malignancies using dendritic cells.

    Van de Velde, Ann L R; Berneman, Zwi N; Van Tendeloo, Viggo F I

    2008-03-01

    The arsenal of therapeutic weapons against hematological malignancies is constantly growing. Unravelling the secrets of tumor immunobiology has allowed researchers to manipulate the immune system in order to stimulate tumor immunity or to bypass tumor-induced immunosuppression. An area of great interest is active specific immunotherapy where dendritic cell (DC)-based therapeutic vaccines for cancer have definitely grabbed the spotlight. DC are intensively investigated as cellular adjuvants to harness the immune system to fight off cancer by augmenting the number and effector functions of tumor-specific CD8+ cytotoxic T lymphocytes. In the present review we present a comprehensive synopsis and an update of the use of DC in hematological malignancies. In the future, more basic research as well as more clinical trials are warranted to fully establish the value of DC vaccination as an adjuvant therapy for modern hematological oncology. PMID:18390412

  13. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

    2011-04-26

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

  14. Role of Dendritic Cells in Immune Dysfunction

    Savary, Cherylyn A.

    1998-01-01

    The specific aims of the project were: (1) Application of the NASA bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC). (2) Compare the frequency and function of DC in normal donors and immunocompromised cancer patients. (3) Analyze the effectiveness of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in a murine model of experimental fungal disease. Our investigations have provided new insight into DC immunobiology and have led to the development of methodology to evaluate DC in blood of normal donors and patients. Information gained from these studies has broadened our understanding of possible mechanisms involved in the immune dysfunction of space travelers and earth-bound cancer patients, and could contribute to the design of novel therapies to restore/preserve immunity in these individuals. Several new avenues of investigation were also revealed. The results of studies completed during Round 2 are summarized.

  15. Plasmacytoid Dendritic Cells: From Heart to Vessels

    Rosalinda Sorrentino

    2010-01-01

    Full Text Available Cardiovascular diseases, formerly only attributed to the alterations of the stromal component, are now recognized as immune-based pathologies. Plasmacytoid Dendritic Cells (pDCs are important immune orchestrators in heart and vessels. They highly produce IFN type I that promote the polarization of T cells towards a Th1 phenotype; however, pDCs can also participate to suppressive networks via the recruitment of T regulatory cells that downmodulate proinflammatory responses. pDCs populate the vessel wall layers during pathological conditions, such as atherosclerosis. It is thus clear that a better identification of pDCs activity in cardiovascular diseases can not only elucidate pathological mechanisms but also lead to new therapeutic approaches.

  16. Platinum dendritic nanoparticles with magnetic behavior

    Magnetic nanoparticles have attracted increasing attention for biomedical applications in magnetic resonance imaging, high frequency magnetic field hyperthermia therapies, and magnetic-field-gradient-targeted drug delivery. In this study, three-dimensional (3D) platinum nanostructures with large surface area that features magnetic behavior have been demonstrated. The well-developed 3D nanodendrites consist of plentiful interconnected nano-arms ∼4 nm in size. The magnetic behavior of the 3D dendritic Pt nanoparticles is contributed by the localization of surface electrons due to strongly bonded oxygen/Pluronic F127 and the local magnetic moment induced by oxygen vacancies on the neighboring Pt and O atoms. The magnetization of the nanoparticles exhibits a mixed paramagnetic and ferromagnetic state, originating from the core and surface, respectively. The 3D nanodendrite structure is suitable for surface modification and high amounts of drug loading if the transition temperature was enhanced to room temperature properly.

  17. Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes.

    Zagha, Edward; Manita, Satoshi; Ross, William N; Rudy, Bernardo

    2010-06-01

    Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca(2+) spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca(2+) spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca(2+)](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca(2+) signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca(2+) influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease. PMID:20357073

  18. Probiotics, dendritic cells and bladder cancer.

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette

  19. GATA2 regulates dendritic cell differentiation.

    Onodera, Koichi; Fujiwara, Tohru; Onishi, Yasushi; Itoh-Nakadai, Ari; Okitsu, Yoko; Fukuhara, Noriko; Ishizawa, Kenichi; Shimizu, Ritsuko; Yamamoto, Masayuki; Harigae, Hideo

    2016-07-28

    Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germ line GATA2 mutations induce GATA2-deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockout and haploinsufficient mice. Gata2 conditional deficiency significantly reduced the DC count, whereas Gata2 haploinsufficiency did not affect this population. GATA2 was required for the in vitro generation of DCs from Lin(-)Sca-1(+)Kit(+) cells, common myeloid-restricted progenitors, and common dendritic cell precursors, but not common lymphoid-restricted progenitors or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the myeloid pathway of DC differentiation. Moreover, expression profiling demonstrated reduced expression of myeloid-related genes, including mafb, and increased expression of T-lymphocyte-related genes, including Gata3 and Tcf7, in Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer element 190-kb downstream region of Gata3, and a reporter assay exhibited significantly reduced luciferase activity after adding this enhancer region to the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 +190. These results suggest that GATA2 plays an important role in cell-fate specification toward the myeloid vs T-lymphocyte lineage by regulating lineage-specific transcription factors in DC progenitors, thereby contributing to DC differentiation. PMID:27259979

  20. Temporal and spatial variation in the status of acid rivers and potential prevention methods of AS soil-related leaching in peatland forestry

    Saarinen, T.

    2013-01-01

    Abstract This thesis examines temporal and spatial variations in the status of different rivers and streams of western Finland in terms of acidity and sources of acid load derived from the catchment area. It also examines the monitoring of acid runoff water derived from maintenance drainage in peatland forestry and suggests potential mitigation methods. A total of 17 river basins of different sizes in western Finland were selected for study, including rivers affected by both drainage of...

  1. Fatty Acid Composition of Novel Host Jack Pine Do Not Prevent Host Acceptance and Colonization by the Invasive Mountain Pine Beetle and Its Symbiotic Fungus.

    Ishangulyyeva, Guncha; Najar, Ahmed; Curtis, Jonathan M; Erbilgin, Nadir

    2016-01-01

    Fatty acids are major components of plant lipids and can affect growth and development of insect herbivores. Despite a large literature examining the roles of fatty acids in conifers, relatively few studies have tested the effects of fatty acids on insect herbivores and their microbial symbionts. Particularly, whether fatty acids can affect the suitability of conifers for insect herbivores has never been studied before. Thus, we evaluated if composition of fatty acids impede or facilitate colonization of jack pine (Pinus banksiana) by the invasive mountain pine beetle (Dendroctonus ponderosae) and its symbiotic fungus (Grosmannia clavigera). This is the first study to examine the effects of tree fatty acids on any bark beetle species and its symbiotic fungus. In a novel bioassay, we found that plant tissues (hosts and non-host) amended with synthetic fatty acids at concentrations representative of jack pine were compatible with beetle larvae. Likewise, G. clavigera grew in media amended with lipid fractions or synthetic fatty acids at concentrations present in jack pine. In contrast, fatty acids and lipid composition of a non-host were not suitable for the beetle larvae or the fungus. Apparently, concentrations of individual, rather than total, fatty acids determined the suitability of jack pine. Furthermore, sampling of host and non-host tree species across Canada demonstrated that the composition of jack pine fatty acids was similar to the different populations of beetle's historical hosts. These results demonstrate that fatty acids composition compatible with insect herbivores and their microbial symbionts can be important factor defining host suitability to invasive insects. PMID:27583820

  2. Passive Dendrites Enable Single Neurons to Compute Linearly Non-separable Functions

    Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

    2013-01-01

    Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where den...

  3. In-situ observation of a dendrite growth in an aqueous condition and a uranium deposition into a liquid cadmium cathode in an electrowinning system

    A zinc-gallium system was setup to observe the growth process of dendrites and to compare the performance of the stirrers which would prevent a dendrite formation. In a no-stirring condition, zinc was easily deposited on a liquid gallium cathode in the form of dendrites. It was difficult for a paddle stirrer to directly fracture the zinc dendrites to fine particles. However, a harrow stirrer was observed to fracture the dendrite to some extent at high speeds. Not only their rotation speed but also the length of their blades needed to be properly adjusted to enhance their performance. In the uranium-cadmium experiment, the diffusion coefficient of the uranium species was obtained by the cyclic voltammetry method, which is around 1 x 10-5 cm2/s. In a no-stirring condition, most of the uranium deposited at the current densities of 35, 100 and 200 mA/cm2 did not sink into the liquid cadmium cathode

  4. Influence of Skin Epithelial cells and Human Umbilical VEIN CELLS Conditioned Media on Maturation of Type 1 Dendritic Cells(DC1

    M Ganjybakhsh

    2011-06-01

    Full Text Available Introduction: Dendritic cells have a high potential in presentation of antigens and can be generated and manipulated in invitro culture conditions. Dendritic cells(DC are therefore used in cancer immunotherapy, in prevention of graft rejection, treatment of allergy, autoimmune diseases and certain infectious diseases. Methods: Dendritic cell was generated in two stages. IN the first stage, monocyte cells were converted to immature DC affected GM-CSF and IL-4 .In the second stage, dendritic cells were maturated in the presence of supernatant skin epithelial cells(A375 and human umbilical vein endothelial cells(HUVEC and maturation factors. The ability of phagocytosis, expression phenotype, stimulation of T lymphocytes and cytokines was studied. Results: Mature Dendritic cells decreased their power of phagocytosis and increased expression of their surface markers. The ability of T cells stimulation and cytokine production(IL-12 increased . Conclusion: Mixture condition medium of epithelial cells and human skin umbilical vein endothelium cells induces maturation of monocyte-derived DCs. This condition medium improves their phenotype and their functions. The mentioned condition medium generates DC1 and Th1 in vitro.

  5. Uterine epithelial cell regulation of DC-SIGN expression inhibits transmitted/founder HIV-1 trans infection by immature dendritic cells.

    Daniel O Ochiel

    Full Text Available BACKGROUND: Sexual transmission accounts for the majority of HIV-1 infections. In over 75% of cases, infection is initiated by a single variant (transmitted/founder virus. However, the determinants of virus selection during transmission are unknown. Host cell-cell interactions in the mucosa may be critical in regulating susceptibility to infection. We hypothesized in this study that specific immune modulators secreted by uterine epithelial cells modulate susceptibility of dendritic cells (DC to infection with HIV-1. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that uterine epithelial cell secretions (i.e. conditioned medium, CM decreased DC-SIGN expression on immature dendritic cells via a transforming growth factor beta (TGF-β mechanism. Further, CM inhibited dendritic cell-mediated trans infection of HIV-1 expressing envelope proteins of prototypic reference. Similarly, CM inhibited trans infection of HIV-1 constructs expressing envelopes of transmitted/founder viruses, variants that are selected during sexual transmission. In contrast, whereas recombinant TGF- β1 inhibited trans infection of prototypic reference HIV-1 by dendritic cells, TGF-β1 had a minimal effect on trans infection of transmitted/founder variants irrespective of the reporter system used to measure trans infection. CONCLUSIONS/SIGNIFICANCE: Our results provide the first direct evidence for uterine epithelial cell regulation of dendritic cell transmission of infection with reference and transmitted/founder HIV-1 variants. These findings have immediate implications for designing strategies to prevent sexual transmission of HIV-1.

  6. Localization of the M2 muscarinic cholinergic receptor in dendrites, cholinergic terminals, and noncholinergic terminals in the rat basolateral amygdala: An ultrastructural analysis.

    Muller, Jay F; Mascagni, Franco; Zaric, Violeta; Mott, David D; McDonald, Alexander J

    2016-08-15

    Activation of M2 muscarinic receptors (M2Rs) in the rat anterior basolateral nucleus (BLa) is critical for the consolidation of memories of emotionally arousing events. The present investigation used immunocytochemistry at the electron microscopic level to determine which structures in the BLa express M2Rs. In addition, dual localization of M2R and the vesicular acetylcholine transporter protein (VAChT), a marker for cholinergic axons, was performed to determine whether M2R is an autoreceptor in cholinergic axons innervating the BLa. M2R immunoreactivity (M2R-ir) was absent from the perikarya of pyramidal neurons, with the exception of the Golgi complex, but was dense in the proximal dendrites and axon initial segments emanating from these neurons. Most perikarya of nonpyramidal neurons were also M2R-negative. About 95% of dendritic shafts and 60% of dendritic spines were M2 immunoreactive (M2R(+) ). Some M2R(+) dendrites had spines, suggesting that they belonged to pyramidal cells, whereas others had morphological features typical of nonpyramidal neurons. M2R-ir was also seen in axon terminals, most of which formed asymmetrical synapses. The main targets of M2R(+) terminals forming asymmetrical (putative excitatory) synapses were dendritic spines, most of which were M2R(+) . The main targets of M2R(+) terminals forming symmetrical (putative inhibitory or neuromodulatory) synapses were unlabeled perikarya and M2R(+) dendritic shafts. M2R-ir was also seen in VAChT(+) cholinergic terminals, indicating a possible autoreceptor role. These findings suggest that M2R-mediated mechanisms in the BLa are very complex, involving postsynaptic effects in dendrites as well as regulating release of glutamate, γ-aminobutyric acid, and acetylcholine from presynaptic axon terminals. J. Comp. Neurol. 524:2400-2417, 2016. © 2016 Wiley Periodicals, Inc. PMID:26779591

  7. Prevention of cardiac dysfunction, kidney fibrosis and lipid metabolic alterations in l-NAME hypertensive rats by sinapic acid-Role of HMG-CoA reductase.

    Silambarasan, Thangarasu; Manivannan, Jeganathan; Raja, Boobalan; Chatterjee, Suvro

    2016-04-15

    The present study was designed to evaluate the effect of sinapic acid, a bioactive phenolic acid on high blood pressure associated cardiac dysfunction, kidney fibrosis and lipid alterations in N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertensive rats. Sinapic acid was administered to rats orally at a dosage of 40mg/kg everyday for a period of 4 weeks. Sinapic acid treatment significantly decreased mean arterial pressure, left ventricular end diastolic pressure, organ weights (liver and kidney), lipid peroxidation products in tissues (liver and kidney), activities of hepatic marker enzymes and the levels of renal function markers in serum of l-NAME rats. Sinapic acid treatment also significantly increased the level of plasma nitric oxide metabolites, and enzymatic and non-enzymatic antioxidants in tissues of l-NAME rats. Tissue damage was assessed by histopathological examination. Alterations in plasma angiotensin-converting enzyme activity, level of plasma lipoproteins and tissue lipids were corrected by sinapic acid treatment in l-NAME rats. Sinapic acid treatment significantly decreased the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in plasma and liver, whereas the activity of lecithin cholesterol acyl transferase was significantly increased in the plasma of hypertensive rats. Docking result showed the interaction between sinapic acid and HMG-CoA reductase. Sinapic acid has shown best ligand binding energy of -5.5kcal/M. Moreover, in chick embryo model, sinapic acid improved vessel density on chorioallantoic membrane. These results of the present study concludes that sinapic acid acts as a protective agent against hypertension associated cardiac dysfunction, kidney fibrosis and lipid alterations. PMID:26945821

  8. Graft-infiltrating host dendritic cells play a key role in organ transplant rejection.

    Zhuang, Quan; Liu, Quan; Divito, Sherrie J; Zeng, Qiang; Yatim, Karim M; Hughes, Andrew D; Rojas-Canales, Darling M; Nakao, A; Shufesky, William J; Williams, Amanda L; Humar, Rishab; Hoffman, Rosemary A; Shlomchik, Warren D; Oberbarnscheidt, Martin H; Lakkis, Fadi G; Morelli, Adrian E

    2016-01-01

    Successful engraftment of organ transplants has traditionally relied on preventing the activation of recipient (host) T cells. Once T-cell activation has occurred, however, stalling the rejection process becomes increasingly difficult, leading to graft failure. Here we demonstrate that graft-infiltrating, recipient (host) dendritic cells (DCs) play a key role in driving the rejection of transplanted organs by activated (effector) T cells. We show that donor DCs that accompany heart or kidney grafts are rapidly replaced by recipient DCs. The DCs originate from non-classical monocytes and form stable, cognate interactions with effector T cells in the graft. Eliminating recipient DCs reduces the proliferation and survival of graft-infiltrating T cells and abrogates ongoing rejection or rejection mediated by transferred effector T cells. Therefore, host DCs that infiltrate transplanted organs sustain the alloimmune response after T-cell activation has already occurred. Targeting these cells provides a means for preventing or treating rejection. PMID:27554168

  9. Actin Remodeling and Polymerization Forces Control Dendritic Spine Morphology

    Miermans, Karsten; Storm, Cornelis; Hoogenraad, Casper

    2015-01-01

    Dendritic spines are small membranous structures that protrude from the neuronal dendrite. Each spine contains a synaptic contact site that may connect its parent dendrite to the axons of neighboring neurons. Dendritic spines are markedly distinct in shape and size, and certain types of stimulation prompt spines to evolve, in fairly predictable fashion, from thin nascent morphologies to the mushroom-like shapes associated with mature spines. This striking progression is coincident with the (re)configuration of the neuronal network during early development, learning and memory formation, and has been conjectured to be part of the machinery that encodes these processes at the scale of individual neuronal connections. It is well established that the structural plasticity of spines is strongly dependent upon the actin cytoskeleton inside the spine. A general framework that details the precise role of actin in directing the transitions between the various spine shapes is lacking. We address this issue, and present...

  10. CD163 positive subsets of blood dendritic cells

    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh; Møller, Bjarne Kuno

    CD163 and CD91 are scavenging receptors with highly increased expression during the differentiation of monocytes into the anti-inflammatory macrophage phenotype. In addition, CD91 is expressed in monocyte-derived dendritic cells (MoDCs), where the receptor is suggested to be important for...... internalization of CD91-targeted antigens to be presented on the dendritic cell surface for T-cell stimulation. Despite their overlap in functionality, the expression of CD91 and CD163 has never been compared and the expression of CD163 in the monocyte-dendritic cell lineage is not yet characterized. CD163...... expression in dendritic cells (DCs) was investigated using multicolor flow cytometry in peripheral blood from 31 healthy donors and 15 HIV-1 patients in addition to umbilical cord blood from 5 newborn infants. Total RNA was isolated from MACS purified DCs and CD163 mRNA was determined with real-time reverse...

  11. Supramolecular effects in dendritic systems containing photoactive groups

    GIANLUCA CAMILLO AZZELLINI

    2000-03-01

    Full Text Available In this article are described dendritic structures containing photoactive groups at the surface or in the core. The observed supramolecular effects can be attributed to the nature of the photoactive group and their location in the dendritic architecture. The peripheric azobenzene groups in these dendrimeric compounds can be regarded as single residues that retain the spectroscopic and photochemical properties of free azobenzene moiety. The E and Z forms of higher generation dendrimer, functionalized with azobenzene groups, show different host ability towards eosin dye, suggesting the possibility of using such dendrimer in photocontrolled host-guest systems. The photophysical properties of many dendritic-bipyridine ruthenium complexes have been investigated. Particularly in aerated medium more intense emission and a longer excited-state lifetime are observed as compared to the parent unsubstituted bipyridine ruthenium complexes. These differences can be attributed to a shielding effect towards dioxygen quenching originated by the dendritic branches.

  12. CUB and Sushi multiple domains 3 regulates dendrite development.

    Mizukami, Tomoharu; Kohno, Takao; Hattori, Mitsuharu

    2016-09-01

    CUB and Sushi multiple domains 3 (CSMD3) is a large protein expressed in fetal and adult brain. Recently, mutations of the CSMD3 gene were identified in schizophrenia and autism patients. However, biochemical properties and functions of the CSMD3 protein remain unknown. Here, we demonstrate that CSMD3 is an oligomeric type I transmembrane protein localized in the apical dendrites of hippocampal pyramidal neurons in the postnatal brain. In cultured hippocampal neurons, CSMD3 is expressed only after 7 days in vitro. Overexpression of CSMD3 induced dendritic branching in hippocampal neurons. Regulation of dendritic morphology by CSMD3 depended on the presence of its extracellular region, while CSMD3 intracellular region was dispensable for this activity. These results suggest that CSMD3 acts as a co-receptor of an unidentified membrane protein to regulate dendrite development. Therefore, malfunctions of CSMD3 may be one of the factors in the pathogenesis of psychiatric disorders. PMID:27033969

  13. Iso-response methods provide direct insight into dendritic computations.

    Stefan Häusler

    2014-04-01

    These results demonstrate that iso-response methods are well suited to unravel complex dendritic computations in model neurons and that they can provide a powerful tool for experimental research with applications in multi-patch or optogenetic recordings.

  14. Dendritic Cells, Viruses, and the Development of Atopic Disease

    Jonathan S. Tam

    2012-01-01

    Full Text Available Dendritic cells are important residents of the lung environment. They have been associated with asthma and other inflammatory diseases of the airways. In addition to their antigen-presenting functions, dendritic cells have the ability to modulate the lung environment to promote atopic disease. While it has long been known that respiratory viral infections associate with the development and exacerbation of atopic diseases, the exact mechanisms have been unclear. Recent studies have begun to show the critical importance of the dendritic cell in this process. This paper focuses on these data demonstrating how different populations of dendritic cells are capable of bridging the adaptive and innate immune systems, ultimately leading to the translation of viral illness into atopic disease.

  15. Facile colloidal coating of polystyrene nanospheres with tunable gold dendritic patches

    Bao, Huixin; Bihr, Timo; Smith, Ana-Sunčana; Klupp Taylor, Robin N.

    2014-03-01

    Patchy particles comprise regions of differing material or chemical functionality on otherwise isotropic cores. To meet the great potential of these anisotropic structures in a wide range of application fields, completely new approaches are sought for the scalable and tunable production of patchy particles, particularly those with nanoscale dimensions. In this paper the synthesis of patchy particles via a simple colloidal route is investigated. Using surfactant-free cationic polystyrene nanospheres as core particles, gold patches are produced through the in situ reduction of chloroauric acid with ascorbic acid. The fact that such nanostructured metal patches can be heterogeneously nucleated on polymer nanospheres is related to the electrostatic interaction between core and metal precursor. Furthermore, the lateral expansion of the gold patches over the polystyrene surface is facilitated by an excess of ascorbic acid. The morphology of the patches is highly dendritic and process-induced variations in the structure are related to gold surface mobility using Monte Carlo simulations based on the diffusion limited aggregation principle. Considering the pH dependent behaviour of ascorbic acid it is possible to predict the moiety which most likely adsorbs to the polymer surface and promotes gold surface diffusion. This enables the judicious adjustment of the pH to also obtain non-dendritic patches. On account of the plasmonic behaviour of gold, the patchy particles have morphology-dependent optical properties. The systematic development of the synthetic approach described here is expected to lay a foundation for the development of functional materials based on the self- or directed-assembly of nanoscale building blocks with anisotropic interactions and properties.Patchy particles comprise regions of differing material or chemical functionality on otherwise isotropic cores. To meet the great potential of these anisotropic structures in a wide range of application fields

  16. mRNA for the EAAC1 Subtype of Glutamate Transporter is Present in Neuronal Dendrites In Vitro and Dramatically Increases In Vivo After a Seizure

    Ross, John R.; Porter, Brenda E.; Buckley, Peter T.; Eberwine, James H.; Robinson, Michael B.

    2010-01-01

    The neuronal Na+-dependent glutamate transporter, excitatory amino acid carrier 1 (EAAC1, also called EAAT3), has been implicated in the control of synaptic spillover of glutamate, synaptic plasticity, and the import of cysteine for neuronal synthesis of glutathione. EAAC1 protein is observed in both perisynaptic regions of the synapse and in neuronal cell bodies. Although amino acid residues in the carboxyl terminal tail have been implicated in the dendritic targeting of EAAC1 protein, it is...

  17. Networks of Polarized Actin Filaments in the Axon Initial Segment Provide a Mechanism for Sorting Axonal and Dendritic Proteins

    Kaori Watanabe

    2012-12-01

    Full Text Available Trafficking of proteins specifically to the axonal or somatodendritic membrane allows neurons to establish and maintain polarized compartments with distinct morphology and function. Diverse evidence suggests that an actin-dependent vesicle filter within the axon initial segment (AIS plays a critical role in polarized trafficking; however, no distinctive actin-based structures capable of comprising such a filter have been found within the AIS. Here, using correlative light and scanning electron microscopy, we visualized networks of actin filaments several microns wide within the AIS of cortical neurons in culture. Individual filaments within these patches are predominantly oriented with their plus ends facing toward the cell body, consistent with models of filter selectivity. Vesicles carrying dendritic proteins are much more likely to stop in regions occupied by the actin patches than in other regions, indicating that the patches likely prevent movement of dendritic proteins to the axon and thereby act as a vesicle filter.

  18. Dysfunctional epileptic neuronal circuits and dysmorphic dendritic spines are mitigated by platelet-activating factor receptor antagonism

    Musto, Alberto E.; Rosencrans, Robert F.; Walker, Chelsey P.; Bhattacharjee, Surjyadipta; Raulji, Chittalsinh M.; Belayev, Ludmila; Fang, Zhide; Gordon, William C.; Bazan, Nicolas G.

    2016-01-01

    Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15–16 weeks after LE using multi-array silicon probe electrodes implanted in the dorsal hippocampus, are reduced in PAF-r antagonist-treated mice. We suggest that over-activation of PAF-r signaling induces aberrant neuronal plasticity in LE and leads to chronic dysfunctional neuronal circuitry that mediates epilepsy. PMID:27444269

  19. Human plasmacytoid dendritic cells: from molecules to intercellular communication network

    Till Sebastian Manuel Mathan; Carl Gustav Figdor; Sonja Ingrid Buschow

    2013-01-01

    Plasmacytoid Dendritic Cells (pDCs) are a specific subset of naturally occurring dendritic cells, that secrete large amounts of Type I interferon and play an important role in the immune response against viral infection. Several studies have highlighted that they are also effective antigen presenting cells (APCs), making them an interesting target for immunotherapy against cancer. However, the modes of action of pDCs are not restricted to antigen presentation and IFN secretion alone. In this ...

  20. Human Plasmacytoid Dendritic Cells: From Molecules to Intercellular Communication Network

    Mathan, Till S. M.; Figdor, Carl G.; Buschow, Sonja I.

    2013-01-01

    Plasmacytoid dendritic cells (pDCs) are a specific subset of naturally occurring dendritic cells, that secrete large amounts of Type I interferon and play an important role in the immune response against viral infection. Several studies have highlighted that they are also effective antigen presenting cells, making them an interesting target for immunotherapy against cancer. However, the modes of action of pDCs are not restricted to antigen presentation and IFN secretion alone. In this review ...

  1. Follicular dendritic cell sarcoma of the pharyngeal region

    HU, TENGPENG; Wang, Xinhua; Yu, Chang; YAN, JIAQIN; ZHANG, XUNDONG; Li, Ling; Li, Xin; Zhang, Lei; Wu, Jingjing; MA, WANG; Li, Wencai; Wang, Guannan; ZHAO, WUGAN; GAO, XIANZHENG; Zhang, Dandan

    2013-01-01

    Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm arising most commonly from follicular dendritic cells in the lymph nodes. It is exceedingly rare in extranodal sites, particularly in the pharyngeal region. The present study reports 3 cases occurring in the pharyngeal region. Case 1 had tonsil and cervical lymph node involvement, while case 3 also had tonsil involvement. Cases 1 and 3 relapsed locally at 3 and 17 months after surgery, respectively. Case 2 was diagnosed with a tumor ...

  2. Interstitial and Langerhans' dendritic cells in chronic periodontitis and gingivitis

    Patricia Ramos Cury; Cristiane Furuse; Ana Elisa Amaro Rodrigues; José Alexandre Barbuto; Cavalcanti de Araújo; Ney Soares de Araújo

    2008-01-01

    The aim of the present study was to compare quantitatively the distribution of dendritic cell subpopulations in chronic periodontitis and gingivitis. Fourteen biopsies from patients with chronic periodontitis and fifteen from patients with gingivitis were studied. An immunoperoxidase technique was used to quantify the number of Langerhans' cells (CD1a) and interstitial dendritic cells (factor XIIIa) in the oral and sulcular and junctional/pocket epithelia and in the lamina propria. A greater ...

  3. Information Fusion for Anomaly Detection with the Dendritic Cell Algorithm

    Greensmith, Julie; Aickelin, Uwe; Tedesco, Gianni

    2010-01-01

    Dendritic cells are antigen presenting cells that provide a vital link between the innate and adaptive immune system, providing the initial detection of pathogenic invaders. Research into this family of cells has revealed that they perform information fusion which directs immune responses. We have derived a Dendritic Cell Algorithm based on the functionality of these cells, by modelling the biological signals and differentiation pathways to build a control mechanism for an artificial im...

  4. Dendritic Cells and Innate Immunity in Kidney Transplantation

    Zhuang, Quan; Lakkis, Fadi G.

    2015-01-01

    Summary This review summarizes emerging concepts related to the roles of dendritic cells and innate immunity in organ transplant rejection. First, it highlights the primary role that recipient, rather than donor, dendritic cells have in rejection and reviews their origin and function in the transplanted kidney. Second, it introduces the novel concept that recognition of allogeneic non-self by host monocytes (referred to here as innate allorecognition) is necessary for initiating rejection by ...

  5. 酸雨对我国生态环境的危害及防治对策%THE HARMFULNESS OF ACID RAIN TO AGRICULTURALECO-ENVIRONMFENT IN CHINA AND THECORRESPONDING PREVENTIVE COUNTERMEASURES

    张士功; 张华

    2001-01-01

    The viewpoints that the harnmfulness of acid rain to macro-agriculture is one of the most serious 10environmental problems were put forward at the 3rd international symposium on environmental protection in 1996.With the development of modem industry,following the North Europe and North America,China has became the 3rd largest acid rain area in the world,and 40% of her area is harmed by acid rain.Acid rain already has become one of the main factors restraining sustainable development of economy in China.Based on the studies of harmfulness of acid rain to agricultural eeo-environment and macro-agriculture in China,the relative preventive countermeasures were presented.%随着现代工业的发展,我国已成为继北欧和北美之后的第三大酸雨区,占国土总面积的40%的地区受到酸雨的危害。酸雨问题已成为制约我国经济可持续发展的主要因素之一。文章从农业可持续发展角度出发,在分析酸雨对我国大农业危害的基础上,提出了酸雨防治的对策建议。

  6. Dendritic bundles, minicolumns, columns, and cortical output units

    Giorgio Innocenti

    2010-03-01

    Full Text Available The search for the fundamental building block of the cerebral cortex has highlighted three structures, perpendicular to the cortical surface: i columns of neurons with radially invariant response properties, e.g., receptive field position, sensory modality, stimulus orientation or direction, frequency tuning etc. ii minicolumns of radially aligned cell bodies and iii bundles, constituted by the apical dendrites of pyramidal neurons with cell bodies in different layers. The latter were described in detail, and sometimes quantitatively, in several species and areas. It was recently suggested that the dendritic bundles consist of apical dendrites belonging to neurons projecting their axons to specific targets. We review the concept above and suggest that another structural and computational unit of cerebral cortex is the cortical output unit (COU, i.e. an assembly of bundles of apical dendrites and their parent cell bodies including each of the outputs to distant cortical or subcortical structures, of a given cortical locus (area or part of an area. This somato-dendritic assembly receives inputs some of which are common to the whole assembly and determine its radially invariant response properties, others are specific to one or more dendritic bundles, and determine the specific response signature of neurons in the different cortical layers and projecting to different targets.

  7. Strategies for mapping synaptic inputs on dendrites in vivo by combining two-photon microscopy, sharp intracellular recording and pharmacology

    Manuel eLevy

    2012-12-01

    Full Text Available Uncovering the functional properties of individual synaptic inputs on single neurons is critical for understanding the computational role of synapses and dendrites. Previous studies combined whole-cell patch recording to load neurons with a fluorescent calcium indicator and two-photon imaging to map subcellular changes in fluorescence upon sensory stimulation. By hyperpolarizing the neuron below spike threshold, the patch electrode ensured that changes in fluorescence associated with synaptic events were isolated from those caused by back-propagating action potentials. This technique holds promise for determining whether the existence of unique cortical feature maps across different species may be associated with distinct wiring diagrams. However, the use of whole-cell patch for mapping inputs on dendrites is challenging in large mammals, due to brain pulsations and the accumulation of fluorescent dye in the extracellular milieu. Alternatively, sharp intracellular electrodes have been used to label neurons with fluorescent dyes, but the current passing capabilities of these high impedance electrodes may be insufficient to prevent spiking. In this study, we tested whether sharp electrode recording is suitable for mapping functional inputs on dendrites in the cat visual cortex. We compared three different strategies for suppressing visually evoked spikes: (1 hyperpolarization by intracellular current injection, (2 pharmacological blockade of voltage-gated sodium channels by intracellular QX-314, and (3 GABA iontophoresis from a perisomatic electrode glued to the intracellular electrode. We found that functional inputs on dendrites could be successfully imaged using all three strategies. However, the best method for preventing spikes was GABA iontophoresis with low currents (5 to 10 nA, which minimally affected the local circuit. Our methods advance the possibility of determining functional connectivity in preparations where whole-cell patch may be

  8. Electrophilic nitro-fatty acids prevent astrocyte-mediated toxicity to motor neurons in a cell model of familial amyotrophic lateral sclerosis via nuclear factor erythroid 2-related factor activation.

    Diaz-Amarilla, Pablo; Miquel, Ernesto; Trostchansky, Andrés; Trias, Emiliano; Ferreira, Ana M; Freeman, Bruce A; Cassina, Patricia; Barbeito, Luis; Vargas, Marcelo R; Rubbo, Homero

    2016-06-01

    Nitro-fatty acids (NO2-FA) are electrophilic signaling mediators formed in tissues during inflammation, which are able to induce pleiotropic cytoprotective and antioxidant pathways including up regulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) responsive genes. Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons associated to an inflammatory process that usually aggravates the disease progression. In ALS animal models, the activation of the transcription factor Nrf2 in astrocytes confers protection to neighboring neurons. It is currently unknown whether NO2-FA can exert protective activity in ALS through Nrf2 activation. Herein we demonstrate that nitro-arachidonic acid (NO2-AA) or nitro-oleic acid (NO2-OA) administrated to astrocytes expressing the ALS-linked hSOD1(G93A) induce antioxidant phase II enzyme expression through Nrf2 activation concomitant with increasing intracellular glutathione levels. Furthermore, treatment of hSOD1(G93A)-expressing astrocytes with NO2-FA prevented their toxicity to motor neurons. Transfection of siRNA targeted to Nrf2 mRNA supported the involvement of Nrf2 activation in NO2-FA-mediated protective effects. Our results show for the first time that NO2-FA induce a potent Nrf2-dependent antioxidant response in astrocytes capable of preventing motor neurons death in a culture model of ALS. PMID:27012417

  9. Numerical Simulation of Dendritic Growth of Continuously Cast High Carbon Steel

    Wang, Weiling; Luo, Sen; Zhu, Miaoyong

    2015-01-01

    Considering the influence of the latent heat released during the solidification of high carbon liquid steel, a cellular automaton (CA) model coupled with the heat transfer was developed to investigate the growth of equiaxed dendrites which is controlled by the solute diffusion during the continuous casting process. Additionally, the growth of columnar dendrites and primary dendrite arm spacings were predicted and measured. The results show that the CA model is able to describe the growth behavior of equiaxed dendrites, especially at 5 K to 7 K melt undercoolings, and the approach adjusting the cooling medium temperature is reliable to keep the undercooling condition stable for equiaxed dendrites although its hysteresis is reinforced as the pre-set undercooling increases. With the increase of the melt undercooling, the growth of equiaxed dendrites becomes faster, and the thickness of dendritic arms increases slightly, however, the thickness of the diffusion layer in front of dendritic tips keeps constant. The growth of thin and tiny columnar dendrites will be confined due to the competition and absorbed by neighboring strong columnar dendrites, giving rise to the coarsening of columnar dendrites, which is observed both from the experimental observation and the numerical simulation. With the decrease of the cooling intensity, columnar dendrites get sparser, primary dendrite arm spacings increase, and secondary dendritic arms become undeveloped.

  10. Allelopathic potential and ecotoxicity evaluation of gallic and nonanoic acids to prevent cyanobacterial growth in lentic systems: A preliminary mesocosm study.

    Techer, Didier; Fontaine, Pascal; Personne, Aline; Viot, Sandrine; Thomas, Marielle

    2016-03-15

    The increase in anthropogenic nutrient loading affecting many freshwater ecosystems combined with global warming may lead to cyanobacterial blooms on an increasingly frequent basis. Among the various physicochemical and biological methods which have been proposed to rapidly control blue-green algae growth, the use of plant-derived substances such as allelochemicals has gained great interest as an environment-friendly approach. The primary aim of this work was to evaluate the efficiency of gallic and nonanoic acid application to preemptively inhibit cyanobacterial growth in lentic hydrosystems. In order to address the process feasibility under realistic exposure scenarios, thirteen outdoor freshwater mesocosms (unit volume: 3m(3)) were designed, each containing phytoplankton (including local blue-green algae species) and various non-target organisms from higher trophic levels (Physa, Lymnaea, Gammarus, and Scardinius erythrophthalmus). After an 8-week mesocosm stabilization period, a full factorial design based on the presence/absence of gallic acid (GA) and nonanoic acid (NA) (including a control group) was implemented into the exposure tanks. Regular monitoring of major phytoplankton taxa was conducted during a 28-day experiment using an on-line fluorometer. The main results suggested that gallic acid was more efficient than nonanoic acid at limiting cyanobacterial growth at concentrations as low as 1 mg L(-1). Successive gallic acid applications (at 1, 2 and 4 mg L(-1)) at the early stages of cyanobacterial growth did not allow the complete elimination of blue-green algae from the mesocosms. However, the specificity of the allelopathic effect of gallic acid towards cyanobacteria was compatible with the maintenance of a primary productivity in the treated tanks as indicated by the photoautotrophic growth of other algal taxa. Finally, no biomarker induction signal could be reported in non-target species. Further gallic acid application trials in lentic systems such

  11. Carnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase.

    Gao, Xuefei; Li, Kuai; Hui, Xiaoyan; Kong, Xiangping; Sweeney, Gary; Wang, Yu; Xu, Aimin; Teng, Maikun; Liu, Pentao; Wu, Donghai

    2011-05-01

    The adipocyte is the principal cell type for fat storage. CPT1 (carnitine palmitoyltransferase-1) is the rate-limiting enzyme for fatty acid β-oxidation, but the physiological role of CPT1 in adipocytes remains unclear. In the present study, we focused on the specific role of CPT1A in the normal functioning of adipocytes. Three 3T3-L1 adipocyte cell lines stably expressing hCPT1A (human CPT1A) cDNA, mouse CPT1A shRNA (short-hairpin RNA) or GFP (green fluorescent protein) were generated and the biological functions of these cell lines were characterized. Alteration in CPT1 activity, either by ectopic overexpression or pharmacological inhibition using etomoxir, did not affect adipocyte differentiation. However, overexpression of hCPT1A significantly reduced the content of intracellular NEFAs (non-esterified fatty acids) compared with the control cells when adipocytes were challenged with fatty acids. The changes were accompanied by an increase in fatty acid uptake and a decrease in fatty acid release. Interestingly, CPT1A protected against fatty acid-induced insulin resistance and expression of pro-inflammatory adipokines such as TNF-α (tumour necrosis factor-α) and IL-6 (interleukin-6) in adipocytes. Further studies demonstrated that JNK (c-Jun N terminal kinase) activity was substantially suppressed upon CPT1A overexpression, whereas knockdown or pharmacological inhibition of CPT1 caused a significant enhancement of JNK activity. The specific inhibitor of JNK SP600125 largely abolished the changes caused by the shRNA- and etomoxir-mediated decrease in CPT1 activity. Moreover, C2C12 myocytes co-cultured with adipocytes pre-treated with fatty acids displayed altered insulin sensitivity. Taken together, our findings have identified a favourable role for CPT1A in adipocytes to attenuate fatty acid-evoked insulin resistance and inflammation via suppression of JNK. PMID:21348853

  12. Activated protein C modulates the proinflammatory activity of dendritic cells

    Matsumoto T

    2015-05-01

    Full Text Available Takahiro Matsumoto,1,2* Yuki Matsushima,1* Masaaki Toda,1 Ziaurahman Roeen,1 Corina N D'Alessandro-Gabazza,1,5 Josephine A Hinneh,1 Etsuko Harada,1,3 Taro Yasuma,4 Yutaka Yano,4 Masahito Urawa,1,5 Tetsu Kobayashi,5 Osamu Taguchi,5 Esteban C Gabazza1 1Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, 2BONAC Corporation, BIO Factory 4F, Fukuoka, 3Iwade Research Institute of Mycology, 4Department of Endocrinology, Diabetes and Metabolism, 5Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan *These authors contributed equally to this work Background: Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells. Materials and methods: Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells. Results: Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C

  13. Stochastic hybrid model of spontaneous dendritic NMDA spikes

    Following recent advances in imaging techniques and methods of dendritic stimulation, active voltage spikes have been observed in thin dendritic branches of excitatory pyramidal neurons, where the majority of synapses occur. The generation of these dendritic spikes involves both Na+ ion channels and M-methyl-D-aspartate receptor (NMDAR) channels. During strong stimulation of a thin dendrite, the resulting high levels of glutamate, the main excitatory neurotransmitter in the central nervous system and an NMDA agonist, modify the current-voltage (I–V) characteristics of an NMDAR so that it behaves like a voltage-gated Na+ channel. Hence, the NMDARs can fire a regenerative dendritic spike, just as Na+ channels support the initiation of an action potential following membrane depolarization. However, the duration of the dendritic spike is of the order 100 ms rather than 1 ms, since it involves slow unbinding of glutamate from NMDARs rather than activation of hyperpolarizing K+ channels. It has been suggested that dendritic NMDA spikes may play an important role in dendritic computations and provide a cellular substrate for short-term memory. In this paper, we consider a stochastic, conductance-based model of dendritic NMDA spikes, in which the noise originates from the stochastic opening and closing of a finite number of Na+ and NMDA receptor ion channels. The resulting model takes the form of a stochastic hybrid system, in which membrane voltage evolves according to a piecewise deterministic dynamics that is coupled to a jump Markov process describing the opening and closing of the ion channels. We formulate the noise-induced initiation and termination of a dendritic spike in terms of a first-passage time problem, under the assumption that glutamate unbinding is negligible, which we then solve using a combination of WKB methods and singular perturbation theory. Using a stochastic phase-plane analysis we then extend our analysis to take proper account of the

  14. Dendritic cells in inflammatory sinonasal diseases.

    Cao, P-P; Shi, L-L; Xu, K; Yao, Y; Liu, Z

    2016-07-01

    Dendritic cells (DCs) are critical in linking the innate and adaptive immune responses, which have been implicated in the pathogenesis of many immune and inflammatory diseases as well as the development of tumours. The role of DCs in the pathophysiology of lung diseases has been widely studied. However, the phenotype, subset and function of DCs in upper airways under physiological or pathological conditions remain largely undefined. Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two important upper airway diseases with a high worldwide prevalence. Aberrant innate and adaptive immune responses have been considered to play an important role in the pathogenesis of AR and CRS. To this end, understanding the function of DCs in shaping the immune responses in sinonasal mucosa is critical in exploring the pathogenic mechanisms underlying AR and CRS as well as in developing novel therapeutic strategies. This review summarizes the phenotype, subset, function and regulation of DCs in sinonasal mucosa, particularly in the setting of AR and CRS. Furthermore, this review discusses the perspectives for future research and potential clinical utility focusing on DC pathways in the context of AR and CRS. PMID:27159777

  15. Baicalin induced dendritic cell apoptosis in vitro

    HuahuaZhang

    2011-03-01

    Full Text Available This study was aimed to investigate the effects of Baicalin (BA, a major flavonoid constituent found in the herb Baikal skullcap, on dendritic cells (DCs. DCs were generated by culturing murine bone marrow cells for 6 days with granulocyte-macrophage colony-stimulating factor and interleukin-4, and lipopolysaccharide (LPS was added on day 5 to stimulate DCs maturation. The expression levels of DC maturity markers (CD80/CD86 were assessed by flow cytometry using direct immunofluorescence method. Interleukin-12 (IL-12 levels in the culture supernatants were assayed by ELISA. Apoptosis of DCs was analyzed by flow cytometry after Annexin V/propidium iodide staining. The mitochondrial membrane potential changes were measured by using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1. Exposure of DCs to BA (2-50 microM during bone marrow cell differentiation showed no effects on the up-regulation of CD80/CD86 expression on DCs in response to LPS stimulation, but reduced DCs recovery by inducing apoptosis, and significantly inhibited the release of IL-12 to culture supernatants. BA induced DC apoptosis in a time- and dose-dependent way, and immature DCs were more sensitive for BA-induced apoptosis than mature DC. BA also induced mitochondrial membrane potential changes in DCs. These results demonstrate that BA induces selective apoptosis in immature DCs possibly through mitochondria-mediated pathway.

  16. Macrophages and Dendritic Cells: Partners in Atherogenesis.

    Cybulsky, Myron I; Cheong, Cheolho; Robbins, Clinton S

    2016-02-19

    Atherosclerosis is a complex chronic disease. The accumulation of myeloid cells in the arterial intima, including macrophages and dendritic cells (DCs), is a feature of early stages of disease. For decades, it has been known that monocyte recruitment to the intima contributes to the burden of lesion macrophages. Yet, this paradigm may require reevaluation in light of recent advances in understanding of tissue macrophage ontogeny, their capacity for self-renewal, as well as observations that macrophages proliferate throughout atherogenesis and that self-renewal is critical for maintenance of macrophages in advanced lesions. The rate of atherosclerotic lesion formation is profoundly influenced by innate and adaptive immunity, which can be regulated locally within atherosclerotic lesions, as well as in secondary lymphoid organs, the bone marrow and the blood. DCs are important modulators of immunity. Advances in the past decade have cemented our understanding of DC subsets, functions, hematopoietic origin, gene expression patterns, transcription factors critical for differentiation, and provided new tools for study of DC biology. The functions of macrophages and DCs overlap to some extent, thus it is important to reassess the contributions of each of these myeloid cells taking into account strict criteria of cell identification, ontogeny, and determine whether their key roles are within atherosclerotic lesions or secondary lymphoid organs. This review will highlight key aspect of macrophage and DC biology, summarize how these cells participate in different stages of atherogenesis and comment on complexities, controversies, and gaps in knowledge in the field. PMID:26892963

  17. Follicular dendritic cells in health and disease

    Mohey Eldin M El Shikh

    2012-09-01

    Full Text Available Follicular dendritic cells (FDCs are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags in the form of highly immunogenic immune complexes (ICs consisting of Ag plus specific antibody (Ab and/or complement proteins. FDCs multimerise Ags and present them polyvalently to B cells in periodically arranged arrays that extensively crosslink the B cell receptors for Ag (BCRs. FDC-Fc-gamma-RIIB mediates IC periodicity, and FDC-Ag presentation combined with other soluble and membrane bound signals contributed by FDCs, like FDC-BAFF, -IL-6 and -C4bBP, are essential for the induction of the germinal centre (GC reaction, the maintenance of serological memory, and the remarkable ability of FDC-Ags to induce specific Ab responses in the absence of cognate T cell help. On the other hand, FDCs play a negative role in several disease conditions including chronic inflammatory diseases, autoimmune diseases, HIV/AIDS, prion diseases and follicular lymphomas. Compared to other accessory immune cells, FDCs have received little attention, and their functions have not been fully elucidated. This review gives an overview of FDC structure, and recapitulates our current knowledge on the immunoregulatory functions of FDCs in health and disease. A better understanding of FDCs should permit better regulation of Ab responses to suit the therapeutic manipulation of regulated and dysregulated immune responses.

  18. Follicular dendritic cells in health and disease.

    El Shikh, Mohey Eldin M; Pitzalis, Costantino

    2012-01-01

    Follicular dendritic cells (FDCs) are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B-cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags) in the form of highly immunogenic immune complexes (ICs) consisting of Ag plus specific antibody (Ab) and/or complement proteins. FDCs multimerize Ags and present them polyvalently to B-cells in periodically arranged arrays that extensively crosslink the B-cell receptors for Ag (BCRs). FDC-FcγRIIB mediates IC periodicity, and FDC-Ag presentation combined with other soluble and membrane bound signals contributed by FDCs, like FDC-BAFF, -IL-6, and -C4bBP, are essential for the induction of the germinal center (GC) reaction, the maintenance of serological memory, and the remarkable ability of FDC-Ags to induce specific Ab responses in the absence of cognate T-cell help. On the other hand, FDCs play a negative role in several disease conditions including chronic inflammatory diseases, autoimmune diseases, HIV/AIDS, prion diseases, and follicular lymphomas. Compared to other accessory immune cells, FDCs have received little attention, and their functions have not been fully elucidated. This review gives an overview of FDC structure, and recapitulates our current knowledge on the immunoregulatory functions of FDCs in health and disease. A better understanding of FDCs should permit better regulation of Ab responses to suit the therapeutic manipulation of regulated and dysregulated immune responses. PMID:23049531

  19. Sodium pump organization in dendritic spines.

    Blom, Hans; Bernhem, Kristoffer; Brismar, Hjalmar

    2016-10-01

    Advancement in fluorescence imaging with the invention of several super-resolution microscopy modalities (e.g., PALM/STORM and STED) has opened up the possibility of deciphering molecular distributions on the nanoscale. In our quest to better elucidate postsynaptic protein distribution in dendritic spines, we have applied these nanoscopy methods, where generated results could help improve our understanding of neuronal functions. In particular, we have investigated the principal energy transformer in the brain, i.e., the [Formula: see text]-ATPase (or sodium pump), an essential protein responsible for maintaining resting membrane potential and a major controller of intracellular ion homeostasis. In these investigations, we have focused on estimates of protein amount, giving assessments of how variations may depend on labeling strategies, sample analysis, and choice of nanoscopic imaging method, concluding that all can be critical factors for quantification. We present a comparison of these results and discuss the influences this may have for homeostatic sodium regulation in neurons and energy consumption. PMID:27175374

  20. Deciphering dendritic cell heterogenity in immunity

    Michaël eChopin

    2012-02-01

    Full Text Available Dendritic cells (DCs are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific roles in local immunosurveillance, migration and antigen presentation. This division of labor amongst DCs offers great potential to tune the immune response by harnessing subset-specific attributes of DCs in the clinical setting. Until recently, our understanding of DC subsets has been limited and paralleled by poor clinical translation and efficacy. We have now begun to unravel how different DC subsets develop within a complex multilayered system. These finding open up exciting possibilities for targeted manipulation of DC subsets. Furthermore, ground-breaking developments overcoming a major translational obstacle – identification of similar DC populations in mouse and man – now set the stage for significant advances in the field. Here we explore the determinants that underpin cellular and transcriptional heterogeneity within the DC network, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection.

  1. Efficacy of n-3 polyunsaturated fatty acids and feasibility of optimizing preventive strategies in patients at high cardiovascular risk: rationale, design and baseline characteristics of the Rischio and Prevenzione study, a large randomised trial in general practice

    2010-05-01

    Full Text Available Abstract Background The optimization of preventive strategies in patients at high risk of cardiovascular events and the evaluation of bottlenecks and limitations of transferring current guidelines to the real world of clinical practice are important limiting steps to cardiovascular prevention. Treatment with n-3 polyunsaturated fatty acids improves prognosis after myocardial infarction, but evidence of this benefit is lacking in patients at high cardiovascular risk, but without a history of myocardial infarction. Methods/design Patients were eligible if their general practitioner (GP considered them at high cardiovascular risk because of a cardiovascular disease other than myocardial infarction, or multiple risk factors (at least four major risk factors in non-diabetic patients and one in diabetics. Patients were randomly allocated to treatment with n-3 polyunsaturated fatty acids (1 g daily or placebo in a double-blind study and followed up for five years by their GPs to assess the efficacy of the treatment in preventing cardiovascular mortality (including sudden death and hospitalization for cardiovascular reasons. The secondary, epidemiological, aim of the study is to assess whether it is feasible to adopt current guidelines in everyday clinical practice, with a view to optimizing all the available preventive strategies in people at high cardiovascular risk. A nation-wide network of 860 GPs admitted 12,513 patients to the study between February 2004 and March 2007. The mean age was 64 years and 62% were males. Diabetes mellitus plus one or more cardiovascular risk factors was the main inclusion criterion (47%. About 30% of patients were included because of a history of atherosclerotic cardiovascular disease, 21% for four or more risk factors, and less than 1% for other reasons. Discussion The Rischio and Prevenzione (R&P project provides a feasible model to test the efficacy of n-3 polyunsaturated fatty acid therapy in patients at high

  2. Drowning Prevention

    ... Listen Español Text Size Email Print Share Drowning Prevention: Information for Parents Page Content Article Body Drowning ... in very cold water for lengthy periods. Drowning Prevention: Know the Warning Signs These signs may signal ...

  3. Preventing Addiction.

    Moore, Susan Fordney

    The purpose of this paper is to provide the beginning counselor with an overview of prevention concepts. Prevention is a relatively new emphasis in community efforts to stem the rising costs of substance abuse and other high-risk behaviors. The paper discusses agent, host, and environmental prevention models and how they relate to causal theories…

  4. Tolerogenic Dendritic Cells on Transplantation: Immunotherapy Based on Second Signal Blockage

    Priscila de Matos Silva

    2015-01-01

    Full Text Available Dendritic cells (DCs, the most important professional antigen-presenting cells (APC, play crucial role in both immunity and tolerance. It is well known that DCs are able to mount immune responses against foreign antigens and simultaneously tolerate self-antigens. Since DCs can be modulated depending on the surrounding microenvironment, they can act as a bridge between innate and adaptive immunity. However, the mechanisms that support this dual role are not entirely clear. Recent studies have shown that DCs can be manipulated ex vivo in order to trigger their tolerogenic profile, what can be a tool to be used in clinical trials aiming the treatment of various diseases and the prevention of transplant rejection. In this sense, the blockage of costimulatory molecules on DC, in the attempt of inhibiting the second signal in the immunological synapse, can be considered as one of the main strategies under development. This review brings an update on current therapies using tolerogenic dendritic cells modulated with costimulatory blockers with the aim of reducing transplant rejection. However, although there are current clinical trials using tolerogenic DC to treat allograft rejection, the actual challenge is to modulate these cells in order to maintain a permanent tolerogenic profile.

  5. Tolerogenic Dendritic Cells on Transplantation: Immunotherapy Based on Second Signal Blockage.

    Silva, Priscila de Matos; Bier, Julia; Paiatto, Lisiery Negrini; Galdino Albuquerque, Cassia; Lopes Souza, Caique; Fernandes, Luis Gustavo Romani; Tamashiro, Wirla Maria da Silva Cunha; Simioni, Patricia Ucelli

    2015-01-01

    Dendritic cells (DCs), the most important professional antigen-presenting cells (APC), play crucial role in both immunity and tolerance. It is well known that DCs are able to mount immune responses against foreign antigens and simultaneously tolerate self-antigens. Since DCs can be modulated depending on the surrounding microenvironment, they can act as a bridge between innate and adaptive immunity. However, the mechanisms that support this dual role are not entirely clear. Recent studies have shown that DCs can be manipulated ex vivo in order to trigger their tolerogenic profile, what can be a tool to be used in clinical trials aiming the treatment of various diseases and the prevention of transplant rejection. In this sense, the blockage of costimulatory molecules on DC, in the attempt of inhibiting the second signal in the immunological synapse, can be considered as one of the main strategies under development. This review brings an update on current therapies using tolerogenic dendritic cells modulated with costimulatory blockers with the aim of reducing transplant rejection. However, although there are current clinical trials using tolerogenic DC to treat allograft rejection, the actual challenge is to modulate these cells in order to maintain a permanent tolerogenic profile. PMID:26543876

  6. Differentiation and function of human monocyte-derived dendritic cells under the influence of leflunomide

    Stojić-Vukanić Z.

    2011-01-01

    Full Text Available Leflunomide is an immunosuppressive drug effective in experimental models of transplantation and autoimmune diseases and in the treatment of active rheumatoid arthritis (RA. Having in mind that it has been shown that some other immunosuppressive drugs (glucocorticoids, mycophenolate mofetil, sirolimus etc. impair dendritic cell (DC phenotype and function, we investigated the effect of A77 1726, an active metabolite of leflunomide, on the differentiation and function of human monocyte-derived dendritic cells (MDDC in vitro. Immature MDDC were generated by cultivating monocytes in medium supplemented with GM-CSF and IL-4. To induce maturation, immature MDDC were cultured for 2 additional days with LPS. A77 1726 (100 μM was added at the beginning of cultivation. Flow cytometric analysis showed that MDDC differentiated in the presence of A77 1726 exhibited an altered phenotype, with a down-regulated surface expression of CD80, CD86, CD54 and CD40 molecules. Furthermore, the continuous presence of A77 1726 during differentiation and maturation prevented successful maturation, judging by the decreased expression of maturation marker CD83, costimulatory and adhesive molecules on A77 1726-treated mature MDDC. In addition, A77 1726-pretreated MDDC exhibited a poor stimulatory capacity of the allogeneic T cells and a low production of IL-10 and IL-18. These data suggest that leflunomide impairs the differentiation, maturation and function of human MDDC in vitro, which is an additional mechanism of its immunosuppressive effect.

  7. Ultrastrong Polyoxyzole Nanofiber Membranes for Dendrite-Proof and Heat-Resistant Battery Separators.

    Hao, Xiaoming; Zhu, Jian; Jiang, Xiong; Wu, Haitao; Qiao, Jinshuo; Sun, Wang; Wang, Zhenhua; Sun, Kening

    2016-05-11

    Polymeric nanomaterials emerge as key building blocks for engineering materials in a variety of applications. In particular, the high modulus polymeric nanofibers are suitable to prepare flexible yet strong membrane separators to prevent the growth and penetration of lithium dendrites for safe and reliable high energy lithium metal-based batteries. High ionic conductance, scalability, and low cost are other required attributes of the separator important for practical implementations. Available materials so far are difficult to comply with such stringent criteria. Here, we demonstrate a high-yield exfoliation of ultrastrong poly(p-phenylene benzobisoxazole) nanofibers from the Zylon microfibers. A highly scalable blade casting process is used to assemble these nanofibers into nanoporous membranes. These membranes possess ultimate strengths of 525 MPa, Young's moduli of 20 GPa, thermal stability up to 600 °C, and impressively low ionic resistance, enabling their use as dendrite-suppressing membrane separators in electrochemical cells. With such high-performance separators, reliable lithium-metal based batteries operated at 150 °C are also demonstrated. Those polyoxyzole nanofibers would enrich the existing library of strong nanomaterials and serve as a promising material for large-scale and cost-effective safe energy storage. PMID:27105287

  8. Distinguishing linear vs. nonlinear integration in CA1 radial oblique dendrites: it’s about time

    José Francisco eGómez González

    2011-11-01

    Full Text Available It was recently shown that multiple excitatory inputs to CA1 pyramidal neuron dendrites must be activated nearly simultaneously to generate local dendritic spikes and superlinear responses at the soma; even slight input desynchronization prevented local spike initiation (Gasparini, 2006;Losonczy, 2006. This led to the conjecture that CA1 pyramidal neurons may only express their nonlinear integrative capabilities during the highly synchronized sharp waves and ripples that occur during slow wave sleep and resting/consummatory behavior, whereas during active exploration and REM sleep (theta rhythm, inadequate synchronization of excitation would lead CA1 pyramidal cells to function as essentially linear devices. Using a detailed single neuron model, we replicated the experimentally observed synchronization effect for brief inputs mimicking single synaptic release events. When synapses were driven instead by double pulses, more representative of the bursty inputs that occur in vivo, we found that the tolerance for input desynchronization was increased by more than an order of magnitude. The effect depended mainly on paired pulse facilitation of NMDA receptor-mediated responses at Schaffer collateral synapses. Our results suggest that CA1 pyramidal cells could function as nonlinear integrative units in all major hippocampal states.

  9. Facile synthesis of size controllable dendritic mesoporous silica nanoparticles.

    Yu, Ye-Jun; Xing, Jun-Ling; Pang, Jun-Ling; Jiang, Shu-Hua; Lam, Koon-Fung; Yang, Tai-Qun; Xue, Qing-Song; Zhang, Kun; Wu, Peng

    2014-12-24

    The synthesis of highly uniform mesoporous silica nanospheres (MSNs) with dendritic pore channels, particularly ones with particle sizes below 200 nm, is extremely difficult and remains a grand challenge. By a combined synthetic strategy using imidazolium ionic liquids (ILs) with different alkyl lengths as cosurfactants and Pluronic F127 nonionic surfactants as inhibitors of particle growth, the preparation of dendritic MSNs with controlled diameter between 40 and 300 nm was successfully realized. An investigation of dendritic MSNs using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen physisorption revealed that the synthesis of dendritic MSNs at larger size (100-300 nm) strongly depends on the alkyl lengths of cationic imidazolium ILs; while the average size of dendritic MSNs can be controlled within the range of 40-100 nm by varying the amount of Pluronic F127. The Au@MSNs can be used as a catalyst for the reduction of 4-nitrophenol by NaBH4 into 4-aminophenol and exhibit excellent catalytic performance. The present discovery of the extended synthesis conditions offers reproducible, facile, and large-scale synthesis of the monodisperse spherical MSNs with precise size control and, thus, has vast prospects for future applications of ultrafine mesostructured nanoparticle materials in catalysis and biomedicine. PMID:25454255

  10. Human intestinal dendritic cells as controllers of mucosal immunity

    David Bernardo

    2013-06-01

    Full Text Available Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

  11. Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity.

    Molumby, Michael J; Keeler, Austin B; Weiner, Joshua A

    2016-05-01

    Growth of a properly complex dendrite arbor is a key step in neuronal differentiation and a prerequisite for neural circuit formation. Diverse cell surface molecules, such as the clustered protocadherins (Pcdhs), have long been proposed to regulate circuit formation through specific cell-cell interactions. Here, using transgenic and conditional knockout mice to manipulate γ-Pcdh repertoire in the cerebral cortex, we show that the complexity of a neuron's dendritic arbor is determined by homophilic interactions with other cells. Neurons expressing only one of the 22 γ-Pcdhs can exhibit either exuberant or minimal dendrite complexity, depending only on whether surrounding cells express the same isoform. Furthermore, loss of astrocytic γ-Pcdhs, or disruption of astrocyte-neuron homophilic matching, reduces dendrite complexity cell non-autonomously. Our data indicate that γ-Pcdhs act locally to promote dendrite arborization via homophilic matching, and they confirm that connectivity in vivo depends on molecular interactions between neurons and between neurons and astrocytes. PMID:27117416

  12. Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function.

    Vessey, John P; Schoderboeck, Lucia; Gingl, Ewald; Luzi, Ettore; Riefler, Julia; Di Leva, Francesca; Karra, Daniela; Thomas, Sabine; Kiebler, Michael A; Macchi, Paolo

    2010-02-16

    In Drosophila, Pumilio (Pum) is important for neuronal homeostasis as well as learning and memory. We have recently characterized a mammalian homolog of Pum, Pum2, which is found in discrete RNA-containing particles in the somatodendritic compartment of polarized neurons. In this study, we investigated the role of Pum2 in developing and mature neurons by RNA interference. In immature neurons, loss of Pum2 led to enhanced dendritic outgrowth and arborization. In mature neurons, Pum2 down-regulation resulted in a significant reduction in dendritic spines and an increase in elongated dendritic filopodia. Furthermore, we observed an increase in excitatory synapse markers along dendritic shafts. Electrophysiological analysis of synaptic function of neurons lacking Pum2 revealed an increased miniature excitatory postsynaptic current frequency. We then identified two specific mRNAs coding for a known translational regulator, eIF4E, and for a voltage-gated sodium channel, Scn1a, which interacts with Pum2 in immunoprecipitations from brain lysates. Finally, we show that Pum2 regulates translation of the eIF4E mRNA. Taken together, our data reveal a previously undescribed role for Pum2 in dendrite morphogenesis, synapse function, and translational control. PMID:20133610

  13. Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity

    Michael J. Molumby

    2016-05-01

    Full Text Available Growth of a properly complex dendrite arbor is a key step in neuronal differentiation and a prerequisite for neural circuit formation. Diverse cell surface molecules, such as the clustered protocadherins (Pcdhs, have long been proposed to regulate circuit formation through specific cell-cell interactions. Here, using transgenic and conditional knockout mice to manipulate γ-Pcdh repertoire in the cerebral cortex, we show that the complexity of a neuron’s dendritic arbor is determined by homophilic interactions with other cells. Neurons expressing only one of the 22 γ-Pcdhs can exhibit either exuberant or minimal dendrite complexity, depending only on whether surrounding cells express the same isoform. Furthermore, loss of astrocytic γ-Pcdhs, or disruption of astrocyte-neuron homophilic matching, reduces dendrite complexity cell non-autonomously. Our data indicate that γ-Pcdhs act locally to promote dendrite arborization via homophilic matching, and they confirm that connectivity in vivo depends on molecular interactions between neurons and between neurons and astrocytes.

  14. Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

    Bardia F Behabadi

    Full Text Available Neocortical pyramidal neurons (PNs receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.

  15. Composition for preventing salt depositing

    Mikhaylov, S.A.; Balakin, V.M.; Lezhenin, V.V.; Litvinets, Yu.I.; Marinin, N.S.; Talankin, V.S.; Yaryshev, G.M.

    1982-01-01

    A composition is proposed for preventing salt depositing which includes polyethylene-polyamine-N-methyl phosphonic acid or its salt and water. It is distinguished by the fact that in order to improve the degree of prevention of the salt depositing under low temperature conditions, it additionally contains ethylene glycol with the following ratio of components (% by mass): polyethylene polyamine-N-methylphosphonic acid or its salt 5-12; ethylene glycol 30-50; water--the rest.

  16. Glucocorticoid receptor translational isoforms underlie maturational stage-specific glucocorticoid sensitivities of dendritic cells in mice and humans

    Cao, Yun; Bender, Ingrid K.; Konstantinidis, Athanasios K.; Shin, Soon Cheon; Jewell, Christine M.; Cidlowski, John A; Schleimer, Robert P.; Lu, Nick Z.

    2013-01-01

    Mature, but not immature, dendritic cells are sensitive to glucocorticoid-induced apoptosis.Mature, but not immature, dendritic cells express proapoptotic glucocorticoid receptor translational isoforms.

  17. Efficacy of two acidified chlorite postmilking teat disinfectants with sodium dodecylbenzene sulfonic acid on prevention of contagious mastitis using an experimental challenge protocol.

    Oura, L Y; Fox, L K; Warf, C C; Kempt, G K

    2002-01-01

    Two acidified sodium chlorite postmilking teat disinfectants were evaluated for efficacy against Staphylococcus aureus and Streptococcus agalactiae by using National Mastitis Council experimental challenge procedures. The effect of these teat dips on teat skin and teat end condition was also determined. Both dips contained 0.32% sodium chlorite, 1.32% lactic, and 2.5% glycerin. Dips differed in the amount of sodium dodecylbenzene sulfonic acid (0.53 or 0.27%) added as a surfactant. Both dips significantly reduced new intramammary infection (IMI) rates compared with undipped controls. The dip containing 0.53% dodecylbenzene sulfonic acid reduced new IMI by Staph. aureus by 72% and Strep. agalactiae by 75%. The dip containing 0.27% dodecylbenzene sulfonic acid reduced new IMI by Staph. aureus by 100% and by Strep. agalactiae by 88%. Changes in teat skin and teat end condition for treatment and control groups varied in parallel over time. Teats treated with either teat dip had higher mean teat skin and teat end scores than control teats at some weeks. However, teat skin and teat end condition did not tend to change from the start to the completion of the trial. Application of the two new postmilking teat dips was effective in reducing new IMI from contagious mastitis pathogens. (Key words: teat dip, contagious mastitis, chlorous acid) PMID:11860118

  18. Ion channels modulating mouse dendritic cell functions.

    Matzner, Nicole; Zemtsova, Irina M; Nguyen, Thi Xuan; Duszenko, Michael; Shumilina, Ekaterina; Lang, Florian

    2008-11-15

    Ca(2+)-mediated signal transduction pathways play a central regulatory role in dendritic cell (DC) responses to diverse Ags. However, the mechanisms leading to increased [Ca(2+)](i) upon DC activation remained ill-defined. In the present study, LPS treatment (100 ng/ml) of mouse DCs resulted in a rapid increase in [Ca(2+)](i), which was due to Ca(2+) release from intracellular stores and influx of extracellular Ca(2+) across the cell membrane. In whole-cell voltage-clamp experiments, LPS-induced currents exhibited properties similar to the currents through the Ca(2+) release-activated Ca(2+) channels (CRAC). These currents were highly selective for Ca(2+), exhibited a prominent inward rectification of the current-voltage relationship, and showed an anomalous mole fraction and a fast Ca(2+)-dependent inactivation. In addition, the LPS-induced increase of [Ca(2+)](i) was sensitive to margatoxin and ICAGEN-4, both inhibitors of voltage-gated K(+) (Kv) channels Kv1.3 and Kv1.5, respectively. MHC class II expression, CCL21-dependent migration, and TNF-alpha and IL-6 production decreased, whereas phagocytic capacity increased in LPS-stimulated DCs in the presence of both Kv channel inhibitors as well as the I(CRAC) inhibitor SKF-96365. Taken together, our results demonstrate that Ca(2+) influx in LPS-stimulated DCs occurs via Ca(2+) release-activated Ca(2+) channels, is sensitive to Kv channel activity, and is in turn critically important for DC maturation and functions. PMID:18981098

  19. Dendritic cell reprogramming by the hypoxic environment.

    Bosco, Maria Carla; Varesio, Luigi

    2012-12-01

    Myeloid dendritic cells (DCs) are professional antigen-presenting cells central to the orchestration of innate and acquired immunity and the maintenance of self-tolerance. The local microenvironment contributes to the regulation of DC development and functions, and deregulated DC responses may result in amplification of inflammation, loss of tolerance, or establishment of immune escape mechanisms. DC generation from monocytic precursors recruited at sites of inflammation, tissue damage, or neoplasia occurs under condition of low partial oxygen pressure (pO(2), hypoxia). We reviewed the literature addressing the phenotypic and functional changes triggered by hypoxia in monocyte-derived immature (i) and mature (m) DCs. The discussion will revolve around in vitro studies of gene expression profile, which give a comprehensive representation of the complexity of response of these cells to low pO(2). The gene expression pattern of hypoxic DC will be discussed to address the question of the relationship with a specific maturation stage. We will summarize data relative to the regulation of the chemotactic network, which points to a role for hypoxia in promoting a migratory phenotype in iDCs and a highly proinflammatory state in mDCs. Current knowledge of the strict regulatory control exerted by hypoxia on the expression of immune-related cell surface receptors will also be addressed, with a particular focus on a newly identified marker of hypoxic DCs endowed with proinflammatory properties. Furthermore, we discuss the literature on the transcription mechanisms underlying hypoxia-regulated gene expression in DCs, which support a major role for the HIF/HRE pathway. Finally, recent advances shedding light on the in vivo influence of the local hypoxic microenvironment on DCs infiltrating the inflamed joints of juvenile idiopathic arthritis patients are outlined. PMID:22901977

  20. Dendrite-Free Nanocrystalline Zinc Electrodeposition from an Ionic Liquid Containing Nickel Triflate for Rechargeable Zn-Based Batteries.

    Liu, Zhen; Cui, Tong; Pulletikurthi, Giridhar; Lahiri, Abhishek; Carstens, Timo; Olschewski, Mark; Endres, Frank

    2016-02-01

    Metallic zinc is a promising anode material for rechargeable Zn-based batteries. However, the dendritic growth of zinc has prevented practical applications. Herein it is demonstrated that dendrite-free zinc deposits with a nanocrystalline structure can be obtained by using nickel triflate as an additive in a zinc triflate containing ionic liquid. The formation of a thin layer of Zn-Ni alloy (η- and γ-phases) on the surface and in the initial stages of deposition along with the formation of an interfacial layer on the electrode strongly affect the nucleation and growth of zinc. A well-defined and uniform nanocrystalline zinc deposit with particle sizes of about 25 nm was obtained in the presence of Ni(II) . Further, it is shown that the nanocrystalline Zn exhibits a high cycling stability even after 50 deposition/stripping cycles. This strategy of introducing an inorganic metal salt in ionic liquid electrolytes can be considered as an efficient way to obtain dendrite-free zinc. PMID:26822484

  1. Potential drugs which activate nuclear factor E2-related factor 2 signaling to prevent diabetic cardiovascular complications: A focus on fumaric acid esters.

    Zhou, Shanshan; Jin, Jingpeng; Bai, Tao; Sachleben, Leroy R; Cai, Lu; Zheng, Yang

    2015-08-01

    Diabetes and its cardiovascular complications have been a major public health issue. These complications are mainly attributable to a severe imbalance between free radical and reactive oxygen species production and the antioxidant defense systems. Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that controls the basal and inducible expression of a battery of antioxidant enzyme genes and other cyto-protective phase II detoxifying enzymes. As a result, Nrf2 has gained great attention as a promising drug target for preventing diabetic cardiovascular complications. And while animal studies have shown that several Nrf2 activators manifest a potential to efficiently prevent the diabetic complications, their use in humans has not been approved due to the lack of substantial evidence regarding safety and efficacy of the Nrf2 activation. We provide here a brief review of a few clinically-used drugs that can up-regulate Nrf2 with the potential of extending their usage to diabetic patients for the prevention of cardiovascular complications and conclude with a closer inspection of dimethyl fumarate and its mimic members. PMID:26044512

  2. Progress in Modeling Nonlinear Dendritic Evolution in Two and Three Dimensions, and Its Mathematical Justification

    Tanveer, S.; Foster, M. R.

    2002-01-01

    We report progress in three areas of investigation related to dendritic crystal growth. Those items include: 1. Selection of tip features dendritic crystal growth; 2) Investigation of nonlinear evolution for two-sided model; and 3) Rigorous mathematical justification.

  3. All-trans retinoic acid prevents the development of type 1 diabetes by affecting the levels of interferon gamma and interleukin 4 in streptozotocin-induced murine diabetes model.

    Wang, Y; Zhong, Y J; Wang, Y Y; Xing, J; Wang, Z M

    2016-01-01

    The aim of this study was to explore the molecular mechanism by which all-trans retinoic acid (ATRA) prevents type 1 diabetes mellitus (T1DM). Fifty ICR mice were randomly assigned to three groups: prevention group [N = 20; mice received 10 mg/kg ATRA daily for 5 days and then 60 mg/kg streptozotocin (STZ) for 5 days]; diabetic group (N = 20, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for 5 days and then 60 mg/kg STZ for 5 days); and control group (N = 10, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for 5 days and then citrate buffer for 5 days). Blood glucose was measured using blood glucose test strips and serum insulin was measured by radioimmunoassay. Islets cell morphology was assessed by microscopy and ELISA was used to measure the serum levels of interferon gamma (IFN-γ) and interleukin 4 (IL- 4). In the prevention group, blood sugar levels were found to be reduced and serum insulin levels increased compared with the levels in the diabetic group (P levels of IFN-γ and increase the levels of IL-4 as well as the IFN-γ/IL-4 ratio in STZ-treated animals (P levels and increasing IL-4 levels. PMID:27050967

  4. MicroRNA-9 controls dendritic development by targeting REST

    Giusti, Sebastian A; Vogl, Annette M; Brockmann, Marisa M; Vercelli, Claudia A; Rein, Martin L; Trümbach, Dietrich; Wurst, Wolfgang; Cazalla, Demian; Stein, Valentin; Deussing, Jan M; Refojo, Damian

    2014-01-01

    MicroRNAs (miRNAs) are conserved noncoding RNAs that function as posttranscriptional regulators of gene expression. miR-9 is one of the most abundant miRNAs in the brain. Although the function of miR-9 has been well characterized in neural progenitors, its role in dendritic and synaptic development remains largely unknown. In order to target miR-9 in vivo, we developed a transgenic miRNA sponge mouse line allowing conditional inactivation of the miR-9 family in a spatio-temporal-controlled manner. Using this novel approach, we found that miR-9 controls dendritic growth and synaptic transmission in vivo. Furthermore, we demonstrate that miR-9-mediated downregulation of the transcriptional repressor REST is essential for proper dendritic growth. DOI: http://dx.doi.org/10.7554/eLife.02755.001 PMID:25406064

  5. Complete response of metastatic renal cancer with dendritic cell vaccine

    Dall'Oglio Marcos

    2003-01-01

    Full Text Available INTRODUCTION: We report a case of metastatic renal cell carcinoma that presented involution following therapy with dendritic cells. CASE REPORT: Male, 51-year old patient underwent left radical nephrectomy in September 1999 due to renal cell carcinoma, evolved with recurrence of the neoplasia in January 2002, confirmed by resection of the lesion. A vaccine therapy based on dendritic cells was then performed during 5 months (4 applications. After this period, there was occurrence of new lesions, whose resection revealed areas of necrosis and inflammatory infiltrate. DISCUSSION: The outcome of renal cell carcinoma is influenced by prognostic factors that confer more aggressive tumor characteristics. However, in cases of recurrence, the systemic therapy with dendritic cells-based vaccine can be associated with a better outcome with regression of disease.

  6. Robust Type-specific Hemisynapses Induced by Artificial Dendrites

    Kim, Eun Joong; Jeon, Chang Su; Lee, Soo Youn; Hwang, Inseong; Chung, Taek Dong

    2016-04-01

    Type-specificity of synapses, excitatory and inhibitory, regulates information process in neural networks via chemical neurotransmitters. To lay a foundation of synapse-based neural interfaces, artificial dendrites are generated by covering abiotic substrata with ectodomains of type-specific synaptogenic proteins that are C-terminally tagged with biotinylated fluorescent proteins. The excitatory artificial synapses displaying engineered ectodomains of postsynaptic neuroligin-1 (NL1) induce the formation of excitatory presynapses with mixed culture of neurons in various developmental stages, while the inhibitory artificial dendrites displaying engineered NL2 and Slitrk3 induce inhibitory presynapses only with mature neurons. By contrast, if the artificial dendrites are applied to the axonal components of micropatterned neurons, correctly-matched synaptic specificity emerges regardless of the neuronal developmental stages. The hemisynapses retain their initially established type-specificity during neuronal development and maintain their synaptic strength provided live neurons, implying the possibility of durable synapse-based biointerfaces.

  7. Involvement of dendritic cells in autoimmune diseases in children

    Reed Ann M

    2007-07-01

    Full Text Available Abstract Dendritic cells (DCs are professional antigen-presenting cells that are specialized in the uptake of antigens and their transport from peripheral tissues to the lymphoid organs. Over the last decades, the properties of DCs have been intensely studied and much knowledge has been gained about the role of DCs in various diseases and health conditions where the immune system is involved, particularly in cancer and autoimmune disorders. Emerging clues in autoimmune diseases, suggest that dendritic cell dysregulation might be involved in the development of various autoimmune disorders in both adults and children. However, studies investigating a possible contribution of DCs in autoimmune diseases in the pediatric population alone are scanty. The purpose of this review is to give a general overview of the current literature on the relevance of dendritic cells in the most common autoimmune conditions of childhood.

  8. A Model of Dendritic Cell Therapy for Melanoma

    Ami eRadunskaya

    2013-03-01

    Full Text Available Dendritic cells are a promising immunotherapy tool for boosting an individual's antigen specific immune response to cancer. We develop a mathematical model using differential and delay-differential equations to describe the interactions between dendritic cells, effector-immune cells and tumor cells. We account for the trafficking of immune cells between lymph, blood, and tumor compartments. Our model reflects experimental results both for dendritic-cell trafficking and for immune suppression of tumor growth in mice. In addition, in silico experiments suggest more effective immunotherapy treatment protocols can be achieved by modifying dose location and schedule. A sensitivity analysis of the model reveals which patient-specific parameters have the greatest impact on treatment efficacy.

  9. The dendritic density field of a cortical pyramidal cell

    Hermann eCuntz

    2012-02-01

    Full Text Available Much is known about the computation in individual neurons in the cortical column. Also, the selective connectivity between many cortical neuron types has been studied in great detail. But due to the complexity of this microcircuitry its functional role within the cortical column remains a mystery. Some of the wiring behavior between neurons can be interpreted directly from their particular dendritic and axonal shapes. Here, I describe the dendritic density field as one key element that remains to be better understood. I sketch an approach to relate dendritic density fields in general to their underlying potential connectivity schemes. As an example, I show how the characteristic shape of a cortical pyramidal cell appears as a direct consequence of connecting inputs arranged in two separate parallel layers.

  10. Estimation of primary dendrite arm spacings in continuous casting products

    Cicutti, C. [Centro de Investigacion Industrial-FUDETEC, Campana (Argentina); Bilmes, P.; Boeri, R.

    1997-09-01

    The proportion of steels produced by continuous casting has grown drastically during the last two decades, increasing to such an extent that in some countries, several grades of steel are exclusively made by this process. Many investigations recognized the significant influence of the solidification structure on the quality of cast products, and pointed out the importance of the development of appropriate tools to predict the microstructure as a function of thermal and physical parameters. The estimation of secondary dendrite arm spacings in continuously cast steel products has received some attention. However, very little effort has been focused on the prediction of primary dendrite arm spacings, to the best of the authors` knowledge. The main objective of this study is to develop simple expressions to estimate the variation of primary dendrite arm spacings through the section of continuous casting steel products.

  11. 重庆市主城区酸雨的影响因素及防治措施%Influencing Factors of Acid Rain in Main Urban Districts of Chongqing and Its Prevention Measures

    何勇; 熊增连; 陈昌鸣

    2012-01-01

    Through analysis of acid rain pollution situation and changing trend of acid rain concentration in main urban districts of Chongqing in decades, this paper holds that irrational energy structure and industrial layout is the main reason for acid rain pollution in main urban districts of Chongqing and that special meteorology and geological condition make acid rain pollution more serious in the main urban districts of Chongqing. Prevention measures for acid rain based on the real situation of the main urban districts of Chongqing are put forward, which shows that the only way for sustainable development in the main urban districts of Chongqing is the harmonious development between economy and environment.%通过分析重庆市主城区历年来的酸雨污染状况及酸雨浓度的变化趋势,认为不合理的能源结构和产业布局是造成重庆市主城区酸雨污染的主要原因,而特殊的气象和地形条件使主城区的酸雨污染程度进一步加重;并结合主城区的实际情况提出了酸雨的治理措施,表明走经济与环境协调发展是重庆市主城区实现可持续发展的唯一途径。

  12. Role of natural killer and dendritic cell crosstalk in immunomodulation by commensal bacteria probiotics.

    Rizzello, Valeria; Bonaccorsi, Irene; Dongarrà, Maria Luisa; Fink, Lisbeth Nielsen; Ferlazzo, Guido

    2011-01-01

    A cooperative dialogue between natural killer (NK) cells and dendritic cells (DCs) has been elucidated in the last years. They help each other to acquire their complete functions, both in the periphery and in the secondary lymphoid organs. Thus, NK cells' activation by dendritic cells allows the killing of transformed or infected cells in the periphery but may also be important for the generation of adaptive immunity. Indeed, it has been shown that NK cells may play a key role in polarizing a Th1 response upon interaction with DCs exposed to microbial products. This regulatory role of DC/NK cross-talk is of particular importance at mucosal surfaces such as the intestine, where the immune system exists in intimate association with commensal bacteria such as lactic acid bacteria (LAB). We here review NK/DC interactions in the presence of gut-derived commensal bacteria and their role in bacterial strain-dependent immunomodulatory effects. We particularly aim to highlight the ability of distinct species of commensal bacterial probiotics to differently affect the outcome of DC/NK cross-talk and consequently to differently influence the polarization of the adaptive immune response. PMID:21660136

  13. CD4 Receptor is a Key Determinant of Divergent HIV-1 Sensing by Plasmacytoid Dendritic Cells.

    O'Brien, Meagan; Manches, Olivier; Wilen, Craig; Gopal, Ramya; Huq, Rumana; Wu, Vernon; Sunseri, Nicole; Bhardwaj, Nina

    2016-04-01

    Plasmacytoid dendritic cells (pDC) are innate immune cells that sense viral nucleic acids through endosomal Toll-like receptor (TLR) 7/9 to produce type I interferon (IFN) and to differentiate into potent antigen presenting cells (APC). Engagement of TLR7/9 in early endosomes appears to trigger the IRF7 pathway for IFN production whereas engagement in lysosomes seems to trigger the NF-κB pathway for maturation into APC. We showed previously that HIV-1 (HIV) localizes predominantly to early endosomes, not lysosomes, and mainly stimulate IRF7 rather than NF-κB signaling pathways in pDC. This divergent signaling may contribute to disease progression through production of pro-apoptotic and pro-inflammatory IFN and inadequate maturation of pDCs. We now demonstrate that HIV virions may be re-directed to lysosomes for NF-κB signaling by either pseudotyping HIV with influenza hemagglutinin envelope or modification of CD4 mediated-intracellular trafficking. These data suggest that HIV envelope-CD4 receptor interactions drive pDC activation toward an immature IFN producing phenotype rather than differentiation into a mature dendritic cell phenotype. PMID:27082754

  14. Chicken interleukin-21 is costimulatory for T cells and blocks maturation of dendritic cells.

    Rothwell, Lisa; Hu, Tuanjun; Wu, Zhiguang; Kaiser, Pete

    2012-02-01

    In mammals, interleukin-21 (IL-21) is an immunomodulatory cytokine with pleiotropic effects on the proliferation, differentiation and effector functions of T, B, NK and dendritic cells. A cDNA encoding the chicken orthologue of IL-21 (chIL-21) was cloned by RT-PCR from RNA isolated from activated chicken splenocytes and consists of 438 nucleotides, encoding an open reading frame of 145 amino acids (aa). Chicken IL-21 has 20-30% aa identity to its orthologues in mammals, Xenopus and fish, but is more highly conserved within Aves (50-80%). The four alpha-helical bundle structure of mammalian IL-21 appears to be conserved in the predicted chicken protein, as are the four cysteine residues required for the formation of two disulphide bridges. A glutamine residue in aa position 129, which has been implicated in the binding of IL-21 to the IL-2 receptor γ-chain in mammals, is also conserved. ChIL-21 is expressed in most lymphoid tissues, predominantly by CD4+ TCRαβ+ T cells. As in mammals, chIL-21 synergistically enhances T-cell proliferation and inhibits maturation of dendritic cells. PMID:21911004

  15. Anti-CD3 preconditioning separates GVL from GVHD via modulating host dendritic cell and donor T-cell migration in recipients conditioned with TBI

    Li, Nainong; Chen, Ying; He, Wei; Yi, Tangsheng; Zhao, Dongchang; Zhang, Chunyan; Lin, Chia-Lei; Todorov, Ivan; Kandeel, Fouad; Forman, Stephen; Zeng, Defu

    2009-01-01

    Host dendritic cells (DCs) play a critical role in initiating graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL), and separation of GVL from GVHD remains a major challenge in the treatment of hematologic malignancies by allogeneic hematopoietic cell transplantation (HCT). Here, we show that preconditioning with anti-CD3 monoclonal antibody before conditioning with total body irradiation (TBI) prevents GVHD but retains GVL in a HCT model of major histocompatibility complex (MHC)–...

  16. Facile fabrication of dendritic silver structures and their surface enhanced Raman spectroscopic properties

    Jisheng Yang; Zhengdong Jiang

    2015-01-01

    A simple and efficient approach was developed to fabricate silver dendrites by Cu reducing Ag+ in AgNO3 solution. The growth speed, morphologies and structures of the silver dendrites strongly depend on AgNO3 concentration and reaction time. The silver dendrites were formed from nanosheets and the crystal structure is face-centered cubic. Rhodamine 6G was used as probe molecule to show that the silver dendrites have high sensitivity to surface enhanced Raman spectroscopy response.

  17. Age-related dendritic hypertrophy and sexual dimorphism in rat basolateral amygdala

    Rubinow, Marisa J.; Drogos, Lauren L.; Juraska, Janice M.

    2007-01-01

    Little research has examined the influence of aging or sex on anatomical measures in the basolateral amygdala. We quantified spine density and dendritic material in Golgi-Cox stained tissue of the basolateral nucleus in young adult (3–5 months) and aged (20–24 months) male and female Long-Evans rats. Dendritic branching and spine density were measured in principal neurons. Age, but not sex, influenced the dendritic tree, with aged animals displaying significantly more dendritic material. Prev...

  18. Long-term depression is differentially expressed in distinct lamina of hippocampal CA1 dendrites

    Binu eRamachandran

    2015-02-01

    Full Text Available Information storage in CA1 hippocampal pyramidal neurons is compartmentalized in proximal versus distal apical dendrites, cell bodies, and basal dendrites. This compartmentalization is thought to be essential for synaptic integration. Differences in the expression of LTP in each of these compartments have been described, but less is known regarding potential differences in LTD. Here, to directly compare LTD expression in each compartment and to bypass possible differences in input-specificity and stimulation of presynaptic inputs, we used global application of NMDA to induce LTD. We then examined LTD expression in each dendritic sub-region - proximal and distal apical, and basal dendrites - and in cell bodies. Interestingly, we found that distal apical dendrites exhibited the greatest magnitude of LTD of all areas tested and this LTD was maintained, whereas LTD in proximal apical dendrites was not maintained. In basal dendrites, LTD was also maintained, but the magnitude of LTD was less than in distal apical dendrites. Blockade of inhibition blocked LTD maintenance in both distal apical and basal dendrites. Population spikes recorded from the cell body layer correlated with apical dendrite fEPSPs, where LTD was maintained in distal dendrites and decayed in proximal dendrites. On the other hand, LTD of basal dendrite fEPSPs was maintained but population spike responses were not. Thus E-S coupling was distinct in basal and apical dendrites. Our data demonstrate cell autonomous differential information processing in somas and dendritic sub-regions of CA1 pyramidal neurons in the hippocampus, where LTD expression is intrinsic to distinct dendritic regions, and does not depend on the nature of stimulation and input specificity.

  19. N-acetylcysteine and/or ascorbic acid versus placebo to prevent contrast-induced nephropathy in patients undergoing elective cardiac catheterization: The NAPCIN trial; A single-center, prospective, randomized trial

    Mohammed Habib

    2016-01-01

    Full Text Available Several protective measures have been described to prevent contrast-induced nephropathy (CIN. This study is aimed to evaluate the effect of a high dose of N-acetylcysteine (NAC plus hydration, a low dose of NAC plus ascorbic acid and hydration or hydration alone on the prevention of CIN in high-risk patients undergoing elective coronary artery intervention. We conducted a randomized, prospective, placebo-controlled trial of 105 high-risk patients undergoing elective cardiac catheterization. The patients were divided into three different groups: Group A (n = 30, NAC 1200 mg orally before angiography and 1200 mg orally twice daily for three doses along with good hydration; Group B (n = 30, NAC 600 mg before angiography and 600 mg orally twice daily for three doses plus ascorbic acid (3000 mg one dose before angiography and 2000 mg two doses after angiography and good hydration; and Group C (n = 45, hydration with 0.9% saline started just before contrast media injection and continued for 12 h at a rate 1.0 mL/kg/min after angiography or 0.5 mL/kg/h in cases with overt heart failure for 12 h. CIN was defined as an increase in serum creatinine of >25% of baseline or an absolute increase of 0.5 mg/dL above baseline after 48 h. The incidence of CIN was significantly lower in Group A (6.66% compared with Group B (16.66% or Group C (17.77%. The difference between Groups A and B and between Groups A and C was also highly significant (P = 0.001. In contrast, the difference between Groups B and C was not statistically significant (P = 0.37. Our study indicates that high doses of NAC plus hydration provide better protection against CIN than combination therapy of NAC and ascorbic acid plus hydration, or hydration alone.

  20. N-acetylcysteine and/or ascorbic acid versus placebo to prevent contrast-induced nephropathy in patients undergoing elective cardiac catheterization: The NAPCIN trial; A single-center, prospective, randomized trial.

    Habib, Mohammed; Hillis, Alaa; Hammad, Amen

    2016-01-01

    Several protective measures have been described to prevent contrast-induced nephropathy (CIN). This study is aimed to evaluate the effect of a high dose of N-acetylcysteine (NAC) plus hydration, a low dose of NAC plus ascorbic acid and hydration or hydration alone on the prevention of CIN in high-risk patients undergoing elective coronary artery intervention. We conducted a randomized, prospective, placebo-controlled trial of 105 high-risk patients undergoing elective cardiac catheterization. The patients were divided into three different groups: Group A (n=30), NAC 1200 mg orally before angiography and 1200 mg orally twice daily for three doses along with good hydration; Group B (n=30), NAC 600 mg before angiography and 600 mg orally twice daily for three doses plus ascorbic acid (3000 mg one dose) before angiography and 2000 mg two doses after angiography and good hydration; and Group C (n=45), hydration with 0.9% saline started just before contrast media injection and continued for 12 h at a rate 1.0 mL/kg//min after angiography or 0.5 mL/kg/h in cases with overt heart failure for 12 h. CIN was defined as an increase in serum creatinine of >25% of baseline or an absolute increase of 0.5 mg/dL above baseline after 48 h. The incidence of CIN was significantly lower in Group A (6.66%) compared with Group B (16.66%) or Group C (17.77%). The difference between Groups A and B and between Groups A and C was also highly significant (P=0.001). In contrast, the difference between Groups B and C was not statistically significant (P=0.37). Our study indicates that high doses of NAC plus hydration provide better protection against CIN than combination therapy of NAC and ascorbic acid plus hydration, or hydration alone. PMID:26787567