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Sample records for acid prevents dendritic

  1. A role for sodium and chloride in kainic acid-induced beading of inhibitory interneuron dendrites.

    Science.gov (United States)

    Al-Noori, S; Swann, J W

    2000-01-01

    Excitotoxic injury of the dendrites of inhibitory interneurons could lead to decreases in their synaptic activation and explain subsequent local circuit hyperexcitability and epilepsy. A hallmark of dendrotoxicity, at least in principal neurons of the hippocampus and cortex, is focal or varicose swellings of dendritic arbors. In experiments reported here, transient (1h) exposure of hippocampal explant cultures to kainic acid produced marked focal swellings of the dendrites of parvalbumin-immunoreactive pyramidal basket cells in a highly reproducible and dose-dependent manner. At 5mM kainic acid, more than half of the immunopositive apical dendrites in area CA(1) had a beaded appearance. However, the somal volumes of these cells were unaltered by the same treatment. The presence of focal swellings was reversible with kainate washout and was not accompanied by interneuronal cell death. In contrast, exposure to much higher concentrations (300mM) of kainic acid resulted in the total loss of parvalbumin-positive interneurons from explants. Surprisingly, kainic acid-induced dendritic beading does not appear to be mediated by extracellular calcium. Beading was unaltered in the presence of N-methyl-D-aspartate receptor antagonists, the L-type calcium channel antagonist, nimodipine, cadmium, or by removing extracellular calcium. However, blockade of voltage-gated sodium channels by either tetrodotoxin or lidocaine abolished dendritic beading, while the activation of existing voltage-gated sodium channels by veratridine mimicked the kainic acid-induced dendritic beading. Finally, the removal of extracellular chloride prevented the kainic acid-induced dendritic beading.Thus, we suggest that the movement of Na(+) and Cl(-), rather than Ca(2+), into cells underlies the focal swellings of interneuron dendrites in hippocampus.

  2. Sphingosine-1-phosphate receptor inhibition prevents denervation-induced dendritic atrophy.

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    Willems, Laurent M; Zahn, Nadine; Ferreirós, Nerea; Scholich, Klaus; Maggio, Nicola; Deller, Thomas; Vlachos, Andreas

    2016-03-31

    A hallmark of several major neurological diseases is neuronal cell death. In addition to this primary pathology, secondary injury is seen in connected brain regions in which neurons not directly affected by the disease are denervated. These transneuronal effects on the network contribute considerably to the clinical symptoms. Since denervated neurons are viable, they are attractive targets for intervention. Therefore, we studied the role of Sphingosine-1-phosphate (S1P)-receptor signaling, the target of Fingolimod (FTY720), in denervation-induced dendritic atrophy. The entorhinal denervation in vitro model was used to assess dendritic changes of denervated mouse dentate granule cells. Live-cell microscopy of GFP-expressing granule cells in organotypic entorhino-hippocampal slice cultures was employed to follow individual dendritic segments for up to 6 weeks after deafferentation. A set of slice cultures was treated with FTY720 or the S1P-receptor (S1PR) antagonist VPC23019. Lesion-induced changes in S1P (mass spectrometry) and S1PR-mRNA levels (laser microdissection and qPCR) were determined. Denervation caused profound changes in dendritic stability. Dendritic elongation and retraction events were markedly increased, resulting in a net reduction of total dendritic length (TDL) during the first 2 weeks after denervation, followed by a gradual recovery in TDL. These changes were accompanied by an increase in S1P and S1PR1- and S1PR3-mRNA levels, and were not observed in slice cultures treated with FTY720 or VPC23019. We conclude that inhibition of S1PR signaling prevents dendritic destabilization and denervation-induced dendrite loss. These results suggest a novel neuroprotective effect for pharmaceuticals targeting neural S1PR pathways.

  3. SATURATED PICRIC ACID PREVENTS AUTOPHAGIA

    Directory of Open Access Journals (Sweden)

    V Rahimi-Movaghar

    2008-08-01

    Full Text Available "nThe dysesthesia and paresthesia that occurs in laboratory rats after spinal cord injury (SCI results in autophagia. This self-destructive behavior interferes with functional assessments in designed studies and jeopardizes the health of the injured rat. In this study, we evaluated role of saturated picric acid in the prevention of autophagia and self-mutilation. All rats were anesthetized with an intraperitoneal injection of a mixture of ketamine (100 mg/kg and xylazine (10 mg/kg for the SCI procedures. In the first 39 rats, no solution applied to the hind limbs, but in the next 26 cases, we smeared the saturated picric acid on the tail, lower extremities, pelvic, and abdomen of the rats immediately after SCI. In the rats without picric acid, 23 rats died following autophagia, but in the 26 rats with picric acid, there was no autophagia (P < 0.001. Picric acid side effects in skin and gastrointestinal signs such as irritation, redness and diarrhea were not seen in any rat. Saturated picric acid is a topical solution that if used appropriately and carefully, might be safe and effectively prevents autophagia and self-mutilation. When the solution is applied to the lower abdomen and limbs, we presume that its bitterness effectively prevents the rat from licking and biting the limb.

  4. Protective effects of gastrodine on dendritic spines in kainic acid-injured neurons

    Institute of Scientific and Technical Information of China (English)

    Yangfei Ji; Boai Zhang; Yanjie Jia; Guifang Sun; Yu Liu; Tao Peng; Yanru Liu; Xingrong Ma

    2011-01-01

    EphB2 affects neuronal cells by altering the dendritic spines. The present study analyzed the neuroprotective effects of gastrodine by measuring EphB2 expression in rat neural cells cultured in vitro and injured by kainic acid. Gastrodine (12.5, 25, and 50 mg/L) improved morphology in kainic acid-injured neurons, reduced lactate dehydrogenase leakage, decreased neuronal apoptosis, and increased EphB2 expression in neuronal cells. A moderate dose of 25 mg/L gastrodine resulted in the most significant effects. These results suggested that gastrodine suppressed the neurotoxic effects of excitatory amino acids and provided neuroprotection by remodeling neuronal dendritic spines.

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

    Lifescience Database Archive (English)

    Full Text Available 18641647 Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune dise... (.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

  6. Electrochemical Synthesis of Dendritic Polyaniline in BrФnsted Acid Ionic Liquids

    Institute of Scientific and Technical Information of China (English)

    刘宝友; 许丹倩; 徐振元

    2005-01-01

    BrФnsted acid ionic liquids were successfully applied to the electrochemical synthesis of polyaniline films on platinum electrode surfaces by using cyclic voltammetry. The scanning electron micrographs showed distinct changes in morphological structures. The films exhibited quite dense packing and good ordering of polymer dendrite as compared with those prepared using conventional hydrochloric acid, indicating that Bronsting acid ionic liquids might be promising alternatives to dual medium-dopants in the synthesis of conducting polymers.

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

    DEFF Research Database (Denmark)

    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...

  8. Increased levels of acidic calponin during dendritic spine plasticity after pilocarpine-induced seizures.

    Science.gov (United States)

    Ferhat, Lotfi; Esclapez, Monique; Represa, Alfonso; Fattoum, Abdellatif; Shirao, Tomoaki; Ben-Ari, Yezekiel

    2003-01-01

    We have previously shown that, in HEK 293 cells, overexpression of acidic calponin, an actin-binding protein, induces remodeling of actin filaments, leading to a change in cell morphology. In addition, this protein is found in dendritic spines of adult hippocampal neurons. We hypothesized that this protein plays a role in regulating actin-based filaments during dendritic spine plasticity. To assess this hypothesis, the pilocarpine model of temporal lobe epilepsy was selected because an important reorganization of the glutamatergic network, which includes an aberrant sprouting of granule cell axons, neo-synaptogenesis, and dendritic spine remodeling, is well established in the dentate gyrus. This reorganization begins after the initial period of status epilepticus after pilocarpine injection, during the silent period when animals display a normal behavior, and reaches a plateau at the chronic stage when the animals have developed spontaneous recurrent seizures. Our data show that the intensity of immunolabeling for acidic calponin was clearly increased in the inner one-third of the molecular layer of the dentate gyrus, the site of mossy fiber sprouting, and neo-synaptogenesis, at 1 and 2 weeks after pilocarpine injection (silent period) when the reorganization was taking place. In contrast, in chronic pilocarpine-treated animals, when the reorganization was established, the levels of labeling for acidic calponin in the inner molecular layer were similar to those observed in control rats. In addition, double immunostaining studies suggested that the increase in acidic calponin levels occurred within the dendritic spines. Altogether, these results are consistent with an involvement of acidic calponin in dendritic spine plasticity.

  9. Semaphorin-1a prevents Drosophila olfactory projection neuron dendrites from mis-targeting into select antennal lobe regions.

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    Shen, Hung-Chang; Chu, Sao-Yu; Hsu, Tsai-Chi; Wang, Chun-Han; Lin, I-Ya; Yu, Hung-Hsiang

    2017-04-01

    Elucidating how appropriate neurite patterns are generated in neurons of the olfactory system is crucial for comprehending the construction of the olfactory map. In the Drosophila olfactory system, projection neurons (PNs), primarily derived from four neural stem cells (called neuroblasts), populate their cell bodies surrounding to and distribute their dendrites in distinct but overlapping patterns within the primary olfactory center of the brain, the antennal lobe (AL). However, it remains unclear whether the same molecular mechanisms are employed to generate the appropriate dendritic patterns in discrete AL glomeruli among PNs produced from different neuroblasts. Here, by examining a previously explored transmembrane protein Semaphorin-1a (Sema-1a) which was proposed to globally control initial PN dendritic targeting along the dorsolateral-to-ventromedial axis of the AL, we discover a new role for Sema-1a in preventing dendrites of both uni-glomerular and poly-glomerular PNs from aberrant invasion into select AL regions and, intriguingly, this Sema-1a-deficient dendritic mis-targeting phenotype seems to associate with the origins of PNs from which they are derived. Further, ectopic expression of Sema-1a resulted in PN dendritic mis-projection from a select AL region into adjacent glomeruli, strengthening the idea that Sema-1a plays an essential role in preventing abnormal dendritic accumulation in select AL regions. Taken together, these results demonstrate that Sema-1a repulsion keeps dendrites of different types of PNs away from each other, enabling the same types of PN dendrites to be sorted into destined AL glomeruli and permitting for functional assembly of olfactory circuitry.

  10. Depletion of host CCR7(+) dendritic cells prevented donor T cell tissue tropism in anti-CD3-conditioned recipients.

    Science.gov (United States)

    He, Wei; Racine, Jeremy J; Johnston, Heather F; Li, Xiaofan; Li, Nainong; Cassady, Kaniel; Liu, Can; Deng, Ruishu; Martin, Paul; Forman, Stephen; Zeng, Defu

    2014-07-01

    We reported previously that anti-CD3 mAb treatment before hematopoietic cell transplantation (HCT) prevented graft-versus-host disease (GVHD) and preserved graft-versus-leukemia (GVL) effects in mice. These effects were associated with downregulated donor T cell expression of tissue-specific homing and chemokine receptors, marked reduction of donor T cell migration into GVHD target tissues, and deletion of CD103(+) dendritic cells (DCs) in mesenteric lymph nodes (MLN). MLN CD103(+) DCs and peripheral lymph node (PLN) DCs include CCR7(+) and CCR7(-) subsets, but the role of these DC subsets in regulating donor T cell expression of homing and chemokine receptors remain unclear. Here, we show that recipient CCR7(+), but not CCR7(-), DCs in MLN induced donor T cell expression of gut-specific homing and chemokine receptors in a retinoid acid-dependent manner. CCR7 regulated activated DC migration from tissue to draining lymph node, but it was not required for the ability of DCs to induce donor T cell expression of tissue-specific homing and chemokine receptors. Finally, anti-CD3 treatment depleted CCR7(+) but not CCR7(-) DCs by inducing sequential expansion and apoptosis of CCR7(+) DCs in MLN and PLN. Apoptosis of CCR7(+) DCs was associated with DC upregulation of Fas expression and natural killer cell but not T, B, or dendritic cell upregulation of FasL expression in the lymph nodes. These results suggest that depletion of CCR7(+) host-type DCs, with subsequent inhibition of donor T cell migration into GVHD target tissues, can be an effective approach in prevention of acute GVHD and preservation of GVL effects.

  11. Synthesis and catalytic application of amino acid based dendritic macromolecules

    NARCIS (Netherlands)

    Koten, G. van; Gossage, R.A.; Jastrzebski, J.T.B.H.; Ameijde, J. van; Mulders, S.J.E.; Brouwer, Arwin J.; Liskamp, R.M.J.

    1999-01-01

    The use of amino acid based dendrimers as molecular scaffolds for the attachment of catalytically active organometallic Ni ''pincer'' complexes, via a urea functionality, is described; the dendrimer catalysts have comparable activity to their mononuclear (NCN)NiX analogues.

  12. Sertraline and curcumin prevent stress-induced morphological changes of dendrites and neurons in the medial prefrontal cortex of rats.

    Science.gov (United States)

    Noorafshan, A; Abdollahifar, M-A; Karbalay-Doust, S; Asadi-Golshan, R; Rashidian-Rashidabadi, A

    2015-01-01

    Stress induces structural and behavioral impairments. The changes in dendrites and neurons are accompanied by impairments in the tasks mediated by the medial prefrontal cortex (mPFC). The present study was conducted to evaluate the structural changes of the dendrites and neurons of the mPFC after stress using stereological methods. In addition, the effects of a natural and a synthetic substance, i.e., curcumin and sertraline, were evaluated. The rats were divided into 7 groups: stress + distilled water, stress + olive oil, curcumin (100 mg/kg/day), sertraline (10 mg/kg/day), stress + curcumin, stress + sertraline, and control groups. The animals were submitted to chronic variable stress for 56 days. The results showed an average 15% reduction in the length of the dendrites per neuron in the mPFC after stress (p sertraline can prevent the loss of spines and reduction of dendrite length, volume and surface area of the neurons. Sertraline and curcumin can prevent structural changes of the neurons and dendrites induced by stress in the mPFC of rats.

  13. Salvianolic acid B suppresses maturation of human monocyte-derived dendritic cells by activating PPARγ

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    Sun, Aijun; Liu, Hongying; Wang, Shijun; Shi, Dazhuo; Xu, Lei; Cheng, Yong; Wang, Keqiang; Chen, Keji; Zou, Yunzeng; Ge, Junbo

    2011-01-01

    BACKGROUND AND PURPOSE Salvianolic acid B (Sal B), a water-soluble antioxidant derived from a Chinese medicinal herb, is known to be effective in the prevention of atherosclerosis. Here, we tested the hypothesis that the anti-atherosclerotic effect of Sal B might be mediated by suppressing maturation of human monocyte-derived dendritic cells (h-monDC). EXPERIMENTAL APPROACH h-monDC were derived by incubating purified human monocytes with GM-CSF and IL-4. h-monDC were pre-incubated with or without Sal B and stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of PPARγ siRNA. Expression of h-monDC membrane molecules (CD40, CD86, CD1a, HLA-DR) were analysed by FACS, cytokines were measured by elisa and the TLR4-associated signalling pathway was determined by Western blotting. KEY RESULTS Ox-LDL promoted h-monDC maturation, stimulated CD40, CD86, CD1a, HLA-DR expression and IL-12, IL-10, TNF-α production; and up-regulated TLR4 signalling. These effects were inhibited by Sal B. Sal B also triggered PPARγ activation and promoted PPARγ nuclear translocation, attenuated ox-LDL-induced up-regulation of TLR4 and myeloid differentiation primary-response protein 88 and inhibited the downstream p38-MAPK signalling cascade. Knocking down PPARγ with the corresponding siRNA blocked these effects of Sal B. CONCLUSIONS AND IMPLICATIONS Our data suggested that Sal B effectively suppressed maturation of h-monDC induced by ox-LDL through PPARγ activation. PMID:21649636

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

    Institute of Scientific and Technical Information of China (English)

    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.

  15. High-surface step density on dendritic pd leads to exceptional catalytic activity for formic acid oxidation.

    Science.gov (United States)

    Patra, S; Viswanath, B; Barai, K; Ravishankar, N; Munichandraiah, N

    2010-11-01

    Dendritic Pd with corrugated surfaces, obtained by a novel AC technique, exhibits an exceptionally high catalytic activity for the oxidation of formic acid because of the presence of a high density of surface steps. The formation of twinned dendrites leads to a predominance of exposed 111 facets with a high density of surface steps as evident from high resolution electron microscopy investigations. These surface sites provide active sites for the adsorption of the formic acid molecules, thereby enhancing the reaction rate. Control experiments by varying the time of deposition reveal the formation of partially grown dendrites at shorter times indicating that the dendrites were formed by growth rather than particle attachment. Our deposition method opens up interesting possibilities to produce anisotropic nanostructures with corrugated surfaces by exploiting the perturbations involved in the growth process.

  16. Virulent Salmonella enterica serovar typhimurium evades adaptive immunity by preventing dendritic cells from activating T cells.

    Science.gov (United States)

    Tobar, Jaime A; Carreño, Leandro J; Bueno, Susan M; González, Pablo A; Mora, Jorge E; Quezada, Sergio A; Kalergis, Alexis M

    2006-11-01

    Dendritic cells (DCs) constitute the link between innate and adaptive immunity by directly recognizing pathogen-associated molecular patterns (PAMPs) in bacteria and by presenting bacterial antigens to T cells. Recognition of PAMPs renders DCs as professional antigen-presenting cells able to prime naïve T cells and initiate adaptive immunity against bacteria. Therefore, interfering with DC function would promote bacterial survival and dissemination. Understanding the molecular mechanisms that have evolved in virulent bacteria to evade activation of adaptive immunity requires the characterization of virulence factors that interfere with DC function. Salmonella enterica serovar Typhimurium, the causative agent of typhoid-like disease in the mouse, can prevent antigen presentation to T cells by avoiding lysosomal degradation in DCs. Here, we show that this feature of virulent Salmonella applies in vivo to prevent activation of adaptive immunity. In addition, this attribute of virulent Salmonella requires functional expression of a type three secretion system (TTSS) and effector proteins encoded within the Salmonella pathogenicity island 2 (SPI-2). In contrast to wild-type virulent Salmonella, mutant strains carrying specific deletions of SPI-2 genes encoding TTSS components or effectors proteins are targeted to lysosomes and are no longer able to prevent DCs from activating T cells in vitro or in vivo. SPI-2 mutant strains are attenuated in vivo, showing reduced tissue colonization and enhanced T-cell activation, which confers protection against a challenge with wild-type virulent Salmonella. Our data suggest that impairment of DC function by the activity of SPI-2 gene products is crucial for Salmonella pathogenesis.

  17. Plasmacytoid dendritic cells prevent cigarette smoke and Chlamydophila pneumoniae-induced Th2 inflammatory responses.

    Science.gov (United States)

    Sorrentino, Rosalinda; Gray, Pearl; Chen, Shuang; Shimada, Kenichi; Crother, Timothy R; Arditi, Moshe

    2010-10-01

    Smoking promotes the development of allergic asthma and pneumonia. Chlamydophila pneumoniae lung infection is associated with an increased risk for asthma, inducing an immune response regulated by dendritic cells (DCs). This study sought to determine whether exposure to cigarette smoke modulates the functional activity of CD11c-positive DCs in the lung, with and without concomitant C. pneumoniae infection. Bone marrow-derived DCs (BMDCs) were exposed in vitro to cigarette smoke extract (CSE) and/or live C. pneumoniae (Cpn), and then adoptively transferred intratracheally into wild-type mice. Although CSE plus Cpn appeared to exert an additive effect on the production of Th2 cytokines in vitro, we did not see this effect in vivo. However, the adoptive transfer of DCs pulsed with both CSE and C. pneumoniae into the lungs of naive mice led to an influx of plasmacytoid DCs (pDCs) that suppressed the Th2 skewing ability of the transferred BMDCs. The depletion of pDCs by antibody restored the Th2 skewing ability of the BMDCs. The expression of indoleamine-2,3-dioxygenase in the lung was reduced after the depletion of pDCs, and blocking IFN-α in vitro prevented the ability of pDCs to inhibit the Th2 responses induced by myeloid DCs (mDCs), suggesting their potential involvement in the mechanism of altered polarization. In conclusion, exposure to cigarette smoke skews C. pneumoniae-induced mDCs responses toward a Th2 bias in the lung, which is prevented by pDCs. We propose that pDCs may play a major role in the immunosuppressive lung environment in smokers with C. pneumoniae infection.

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

    Lifescience Database Archive (English)

    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 role

  19. Plasmodium falciparum-Derived Uric Acid Precipitates Induce Maturation of Dendritic Cells

    Science.gov (United States)

    van de Hoef, Diana L.; Coppens, Isabelle; Holowka, Thomas; Ben Mamoun, Choukri; Branch, OraLee; Rodriguez, Ana

    2013-01-01

    Malaria is characterized by cyclical fevers and high levels of inflammation, and while an early inflammatory response contributes to parasite clearance, excessive and persistent inflammation can lead to severe forms of the disease. Here, we show that Plasmodium falciparum-infected erythrocytes contain uric acid precipitates in the cytoplasm of the parasitophorous vacuole, which are released when erythrocytes rupture. Uric acid precipitates are highly inflammatory molecules that are considered a danger signal for innate immunity and are the causative agent in gout. We determined that P. falciparum-derived uric acid precipitates induce maturation of human dendritic cells, increasing the expression of cell surface co-stimulatory molecules such as CD80 and CD86, while decreasing human leukocyte antigen-DR expression. In accordance with this, uric acid accounts for a significant proportion of the total stimulatory activity induced by parasite-infected erythrocytes. Moreover, the identification of uric acid precipitates in P. falciparum- and P. vivax-infected erythrocytes obtained directly from malaria patients underscores the in vivo and clinical relevance of our findings. Altogether, our data implicate uric acid precipitates as a potentially important contributor to the innate immune response to Plasmodium infection and may provide a novel target for adjunct therapies. PMID:23405174

  20. Retinoic acid primes human dendritic cells to induce gut-homing, IL-10-producing regulatory T cells

    NARCIS (Netherlands)

    Bakdash, G.; Vogelpoel, L.T.; Capel, T.M. van; Kapsenberg, M.L.; Jong, E.C. de

    2015-01-01

    The vitamin A metabolite all-trans retinoic acid (RA) is an important determinant of intestinal immunity. RA primes dendritic cells (DCs) to express CD103 and produce RA themselves, which induces the gut-homing receptors alpha4beta7 and CCR9 on T cells and amplifies transforming growth factor (TGF)-

  1. Postbiotic Modulation of Retinoic Acid Imprinted Mucosal-like Dendritic Cells by Probiotic Lactobacillus reuteri 17938 In vitro

    Directory of Open Access Journals (Sweden)

    Yeneneh eHaileselassie

    2016-03-01

    Full Text Available Lactobacilli are widely used as probiotics with beneficial effects on infection-associated diarrhea, but also used in clinical trials of e.g. necrotizing enterocolitis and inflammatory bowel diseases. The possibility of using probiotic metabolic products, so called postbiotics, is desirable as it could prevent possible side effects of live bacteria in individuals with a disturbed gut epithelial barrier. Here we studied how Lactobacillus reuteri DSM 17938 cell free supernatant (L. reuteri-CFS influenced retinoic acid (RA-driven mucosal-like dendritic cells (DC and their subsequent effect on T regulatory cells (Treg in vitro. RA clearly imprinted a mucosal-like DC phenotype with higher IL10 production, increased CD103 and CD1d expression and a down-regulated mRNA expression of several inflammatory-associated genes (NFκB1, RELB and TNF. Treatment with L. reuteri-CFS further influenced the tolerogenic phenotype of RA-DC by down-regulating most genes involved in antigen uptake, antigen presentation and signal transduction as well as several chemokine receptors, while up regulating IL10 production. L. reuteri-CFS also augmented CCR7 expression on RA-DC. In co-cultures, RA-DC increased IL10 and FOXP3 expression in Treg, but pre-treatment with L. reuteri-CFS did not further influence the Treg phenotype. In conclusion, L. reuteri-CFS modulates the phenotype and function of mucosal-like DC, implicating its potential application as postbiotic.

  2. Postbiotic Modulation of Retinoic Acid Imprinted Mucosal-like Dendritic Cells by Probiotic Lactobacillus reuteri 17938 In Vitro.

    Science.gov (United States)

    Haileselassie, Yeneneh; Navis, Marit; Vu, Nam; Qazi, Khaleda Rahman; Rethi, Bence; Sverremark-Ekström, Eva

    2016-01-01

    Lactobacilli are widely used as probiotics with beneficial effects on infection-associated diarrhea, but also used in clinical trials of e.g., necrotizing enterocolitis and inflammatory bowel diseases. The possibility of using probiotic metabolic products, so-called postbiotics, is desirable as it could prevent possible side effects of live bacteria in individuals with a disturbed gut epithelial barrier. Here, we studied how Lactobacillus reuteri DSM 17938 cell-free supernatant (L. reuteri-CFS) influenced retinoic acid (RA)-driven mucosal-like dendritic cells (DC) and their subsequent effect on T regulatory cells (Treg) in vitro. RA clearly imprinted a mucosal-like DC phenotype with higher IL10 production, increased CD103 and CD1d expression, and a downregulated mRNA expression of several inflammatory-associated genes (NFκB1, RELB, and TNF). Treatment with L. reuteri-CFS further influenced the tolerogenic phenotype of RA-DC by downregulating most genes involved in antigen uptake, antigen presentation, and signal transduction as well as several chemokine receptors, while upregulating IL10 production. L. reuteri-CFS also augmented CCR7 expression on RA-DC. In cocultures, RA-DC increased IL10 and FOXP3 expression in Treg, but pre-treatment with L. reuteri-CFS did not further influence the Treg phenotype. In conclusion, L. reuteri-CFS modulates the phenotype and function of mucosal-like DC, implicating its potential application as postbiotic.

  3. Niflumic acid renders dendritic cells tolerogenic and up-regulates inhibitory molecules ILT3 and ILT4

    OpenAIRE

    Vidmar, Alenka; Švajger, Urban; Jeras, Matjaž

    2015-01-01

    Niflumic acid is a member of non-steroidal anti-inflammatory agents, from which aspirin was recently shown to inhibit maturation of human-monocyte derived dendritic cells (DCs). DCs are crucial regulators of the immune response, capable of inducing immunity as well as tolerance. In our in vitro study we showed a tolerogenic effect of NFA on phenotype and function of LPSmatured monocyte-derived DCs. Different drug concentrations dose-dependently downregulated the expression of co-stimulatory m...

  4. Human gastric epithelial cells contribute to gastric immune regulation by providing retinoic acid to dendritic cells.

    Science.gov (United States)

    Bimczok, D; Kao, J Y; Zhang, M; Cochrun, S; Mannon, P; Peter, S; Wilcox, C M; Mönkemüller, K E; Harris, P R; Grams, J M; Stahl, R D; Smith, P D; Smythies, L E

    2015-05-01

    Despite the high prevalence of chronic gastritis caused by Helicobacter pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule retinol (ROL), and that gastric epithelial cells express both RA biosynthesis genes and RA response genes, indicative of active RA biosynthesis. Moreover, primary gastric epithelial cells cultured in the presence of ROL synthesized RA in vitro and induced RA biosynthesis in co-cultured monocytes through an RA-dependent mechanism, suggesting that gastric epithelial cells may also confer the ability to generate RA on gastric dendritic cells (DCs). Indeed, DCs purified from gastric mucosa had similar levels of aldehyde dehydrogenase activity and RA biosynthesis gene expression as small intestinal DCs, although gastric DCs lacked CD103. In H. pylori-infected gastric mucosa, gastric RA biosynthesis gene expression was severely disrupted, which may lead to reduced RA signaling and thus contribute to disease progression. Collectively, our results support a critical role for RA in human gastric immune regulation.

  5. Tau Deletion Prevents Stress-Induced Dendritic Atrophy in Prefrontal Cortex: Role of Synaptic Mitochondria.

    Science.gov (United States)

    Lopes, Sofia; Teplytska, Larysa; Vaz-Silva, Joao; Dioli, Chrysoula; Trindade, Rita; Morais, Monica; Webhofer, Christian; Maccarrone, Giuseppina; Almeida, Osborne F X; Turck, Christoph W; Sousa, Nuno; Sotiropoulos, Ioannis; Filiou, Michaela D

    2016-04-12

    Tau protein in dendrites and synapses has been recently implicated in synaptic degeneration and neuronal malfunction. Chronic stress, a well-known inducer of neuronal/synaptic atrophy, triggers hyperphosphorylation of Tau protein and cognitive deficits. However, the cause-effect relationship between these events remains to be established. To test the involvement of Tau in stress-induced impairments of cognition, we investigated the impact of stress on cognitive behavior, neuronal structure, and the synaptic proteome in the prefrontal cortex (PFC) of Tau knock-out (Tau-KO) and wild-type (WT) mice. Whereas exposure to chronic stress resulted in atrophy of apical dendrites and spine loss in PFC neurons as well as significant impairments in working memory in WT mice, such changes were absent in Tau-KO animals. Quantitative proteomic analysis of PFC synaptosomal fractions, combined with transmission electron microscopy analysis, suggested a prominent role for mitochondria in the regulation of the effects of stress. Specifically, chronically stressed animals exhibit Tau-dependent alterations in the levels of proteins involved in mitochondrial transport and oxidative phosphorylation as well as in the synaptic localization of mitochondria in PFC. These findings provide evidence for a causal role of Tau in mediating stress-elicited neuronal atrophy and cognitive impairment and indicate that Tau may exert its effects through synaptic mitochondria.

  6. The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro.

    Science.gov (United States)

    Carlsson, Johan A; Wold, Agnes E; Sandberg, Ann-Sofie; Östman, Sofia M

    2015-01-01

    Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violet low) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells.

  7. The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

    Science.gov (United States)

    Carlsson, Johan A.; Wold, Agnes E.; Sandberg, Ann-Sofie; Östman, Sofia M.

    2015-01-01

    Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells. PMID:26619195

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

    Science.gov (United States)

    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...

  9. Isothermal Dendritic Growth Experiment - PVA Dendrites

    Science.gov (United States)

    1997-01-01

    The Isothermal Dendritic Growth Experiment (IDGE), flown on three Space Shuttle missions, is yielding new insights into virtually all industrially relevant metal and alloy forming operations. IDGE used transparent organic liquids that form dendrites (treelike structures) similar to those inside metal alloys. Comparing Earth-based and space-based dendrite growth velocity, tip size and shape provides a better understanding of the fundamentals of dentritic growth, including gravity's effects. Shalowgraphic images of pivalic acid (PVA) dendrites forming from the melt show the subtle but distinct effects of gravity-driven heat convection on dentritic growth. In orbit, the dendrite grows as its latent heat is liberated by heat conduction. This yields a blunt dendrite tip. On Earth, heat is carried away by both conduction and gravity-driven convection. This yields a sharper dendrite tip. In addition, under terrestrial conditions, the sidebranches growing in the direction of gravity are augmented as gravity helps carry heat out of the way of the growing sidebranches as opposed to microgravity conditions where no augmentation takes place. IDGE was developed by Rensselaer Polytechnic Institute and NASA/Glenn Research Center. Advanced follow-on experiments are being developed for flight on the International Space Station. Photo Credit: NASA/Glenn Research Center

  10. Niflumic acid renders dendritic cells tolerogenic and up-regulates inhibitory molecules ILT3 and ILT4.

    Science.gov (United States)

    Svajger, Urban; Vidmar, Alenka; Jeras, Matjaz

    2008-07-01

    Niflumic acid is a member of non-steroidal anti-inflammatory agents, from which aspirin was recently shown to inhibit maturation of human-monocyte derived dendritic cells (DCs). DCs are crucial regulators of the immune response, capable of inducing immunity as well as tolerance. In our in vitro study we showed a tolerogenic effect of NFA on phenotype and function of LPS-matured monocyte-derived DCs. Different drug concentrations dose-dependently down-regulated the expression of co-stimulatory molecules, particularly CD80 and lowered the expression of dendritic cell marker CD1a. Opposingly, the expressions of two inhibitory surface molecules, associated with tolerogenic DCs, immunoglobulin-like transcripts (ILT)3 and ILT4 were induced in treated DCs. The levels of TNFalpha production by NFA-treated DCs did not change significantly compared to controls, whereas the IL-12p70 and IL-10 production was completely abrogated at higher drug concentrations. However, at lower drug concentrations, the production of IL-12p70 was increased. There were no significant differences in the uptake of FITC labeled dextran by treated DCs compared to untreated cells. In allogeneic cultures with whole CD4+ T cells, dendritic cells differentiated in the presence of NFA appeared poor stimulators of CD4+ T-cell proliferation, even compared to immature DCs (iDCs). These results indicate the immunosuppressive properties of NFA, which may be therapeutically useful in controlling chronic immune and/or inflammatory diseases, by modulating DC characteristics towards tolerogenic DCs.

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

    Science.gov (United States)

    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 340 μm ± 82 μm. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Hyodeoxycholic acid: a new approach to gallstone prevention.

    Science.gov (United States)

    McSherry, C K; Mosbach, E H; Cohen, B I; Une, M; Stenger, R J; Singhal, A K

    1985-01-01

    Hyodeoxycholic acid and its isomer, 6 beta-hyodeoxycholic acid, when added to a lithogenic diet prevented the formation of cholesterol gallstones and crystals in prairie dogs. This beneficial effect occurred in the presence of bile supersaturated with cholesterol. Hyodeoxycholic acid abolished the feedback inhibition of hepatic hydroxymethylglutaryl coenzyme A reductase activity, the rate-limiting enzyme of cholesterol synthesis, and prevented elevations in serum and liver cholesterol observed in animals fed a 0.4 percent cholesterol diet. The gallbladder bile of the animals fed hyodeoxycholic acid and 6 beta-hyodeoxycholic acid contained abundant liquid crystals. This suggests that these bile acids prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones.

  13. SURFACE MODIFICATION OF CaCO3 WITH DENDRITIC CARBOXYLIC ACIDS

    Institute of Scientific and Technical Information of China (English)

    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.

  14. RIG-I Helicase-Independent Pathway in Sendai Virus-Activated Dendritic Cells Is Critical for Preventing Lung Metastasis of AT6.3 Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Tomonori Kato

    2010-11-01

    Full Text Available We recently demonstrated highly efficient antitumor immunity against dermal tumors of B16F10 murine melanoma with the use of dendritic cells (DCs activated by replication-competent, as well as nontransmissible-type, recombinant Sendai viruses (rSeV, and proposed a new concept, “immunostimulatory virotherapy,” for cancer immunotherapy. However, there has been little information on the efficacies of thismethod: 1 inmore clinically relevant situations including metastatic diseases, 2 on other tumor types and other animal species, and 3 on the related molecular/cellular mechanisms. In this study, therefore, we investigated the efficacy of vaccinating DCs activated by fusion gene-deleted nontransmissible rSeV on a rat model of lung metastasis using a highly malignant subline of Dunning R-3327 prostate cancer, AT6.3. rSeV/dF-green fluorescent protein (GFP-activated bone marrow-derived DCs (rSeV/dF-GFP-DC, consistent with results previously observed in murine DCs. Vaccination of rSeV/dF-GFP-DC was highly effective at preventing lung metastasis after intravenous loading of R-3327 tumor cells, compared with the effects observed with immature DCs or lipopolysaccharide-activated DCs. Interestingly, neither CTL activity nor DC trafficking showed any apparent difference among groups. Notably, rSeV/dF-DCs expressing a dominant-negative mutant of retinoic acid-inducible gene I (RIG-I (rSeV/dF-RIGIC-DC, an RNA helicase that recognizes the rSeV genome for inducing type I interferons, largely lost the expression of proinflammatory cytokines without any impairment of antitumor activity. These results indicate the essential role of RIG-I-independent signaling on antimetastatic effect induced by rSeV-activated DCs and may provide important insights to DC-based immunotherapy for advanced malignancies.

  15. Diet-Derived Short Chain Fatty Acids Stimulate Intestinal Epithelial Cells To Induce Mucosal Tolerogenic Dendritic Cells.

    Science.gov (United States)

    Goverse, Gera; Molenaar, Rosalie; Macia, Laurence; Tan, Jian; Erkelens, Martje N; Konijn, Tanja; Knippenberg, Marlene; Cook, Emma C L; Hanekamp, Diana; Veldhoen, Marc; Hartog, Anita; Roeselers, Guus; Mackay, Charles R; Mebius, Reina E

    2017-03-01

    The gastrointestinal tract is continuously exposed to many environmental factors that influence intestinal epithelial cells and the underlying mucosal immune system. In this article, we demonstrate that dietary fiber and short chain fatty acids (SCFAs) induced the expression of the vitamin A-converting enzyme RALDH1 in intestinal epithelial cells in vivo and in vitro, respectively. Furthermore, our data showed that the expression levels of RALDH1 in small intestinal epithelial cells correlated with the activity of vitamin A-converting enzymes in mesenteric lymph node dendritic cells, along with increased numbers of intestinal regulatory T cells and a higher production of luminal IgA. Moreover, we show that the consumption of dietary fiber can alter the composition of SCFA-producing microbiota and SCFA production in the small intestines. In conclusion, our data illustrate that dietary adjustments affect small intestinal epithelial cells and can be used to modulate the mucosal immune system.

  16. Dendritic Cell

    OpenAIRE

    Sevda Söker

    2005-01-01

    Dendritic cells, a member of family of antigen presenting cells, are most effective cells in the primary immune response. Dendritic cells originated from dendron, in mean of tree in the Greek, because of their long and elaborate cytoplasmic branching processes. Dendritic cells constitute approximately 0.1 to 1 percent of the blood’s mononuclear cell. Dendritic cells are widely distributed, and specialized for antigen capture and T cell stimulation. In this article, structures and functions of...

  17. ACETYLSALICYLIC ACID IN THE PREVENTION OF ATHEROTHROMBOTIC EVENTS

    Directory of Open Access Journals (Sweden)

    A. V. Govorin

    2015-12-01

    Full Text Available The results of large-scale clinical trials have convincingly demonstrated the effectiveness of acetylsalicylic acid (ASA in primary and secondary prevention of atherothrombotic events. Studies on the safety of different ASA formulations have been continuing. Magnesium hydroxide included in combined medicine, Сardiomagnil, prevents ASA adverse effects on the gastric mucosa and reduces in severity of dyspeptic symptoms.

  18. ACETYLSALICYLIC ACID IN THE PREVENTION OF ATHEROTHROMBOTIC EVENTS

    Directory of Open Access Journals (Sweden)

    A. V. Govorin

    2012-01-01

    Full Text Available The results of large-scale clinical trials have convincingly demonstrated the effectiveness of acetylsalicylic acid (ASA in primary and secondary prevention of atherothrombotic events. Studies on the safety of different ASA formulations have been continuing. Magnesium hydroxide included in combined medicine, Сardiomagnil, prevents ASA adverse effects on the gastric mucosa and reduces in severity of dyspeptic symptoms.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Direct regulatory immune activity of lactic acid bacteria on Der p 1-pulsed dendritic cells from allergic patients.

    Science.gov (United States)

    Pochard, Pierre; Hammad, Hamida; Ratajczak, Céline; Charbonnier-Hatzfeld, Anne-Sophie; Just, Nicolas; Tonnel, André-Bernard; Pestel, Joël

    2005-07-01

    Lactic acid bacteria (LAB) are suggested to play a regulatory role in the development of allergic reactions. However, their potential effects on dendritic cells (DCs) directing the immune polarization remain unclear. The immunologic effect of Lactobacillus plantarum NCIMB 8826 (LAB1) on monocyte-derived dendritic cells (MD-DCs) from patients allergic to house dust mite was evaluated. MD-DCs were stimulated for 24 hours with the related allergen Der p 1 in the presence or absence of LAB1. Cell-surface markers were assessed by means of FACS analysis, and the key polarizing cytokines IL-12 and IL-10 were quantified. The subsequent regulatory effect of pulsed MD-DCs on naive or memory T cells was evaluated by determining the T-cell cytokine profile. LAB1 induced the maturation of MD-DCs, even if pulsed with Der p 1. Interestingly, after incubation with LAB1 and Der p 1, MD-DCs produced higher amounts of IL-12 than Der p 1-pulsed DCs. Indeed, the T H 2 cytokine (IL-4 and IL-5) production observed when naive or memory autologous T cells were cocultured with Der p 1-pulsed MD-DCs was highly reduced in the presence of LAB1. Finally, in contrast to naive or memory T cells exposed once to Der p 1-pulsed DCs, T cells stimulated by MD-DCs pulsed with Der p 1 and LAB1 failed to produce T H 2 cytokines in response to a new stimulation with Der p 1-pulsed DCs. Thus in the presence of LAB1, MD-DCs from allergic patients tend to reorientate the T-cell response toward a beneficial T H 1 profile.

  1. Folic Acid for the Prevention of Neural Tube Defects : US Preventive Services Task Force Recommendation Statement

    NARCIS (Netherlands)

    Calonge, Ned; Petitti, Diana B.; DeWitt, Thomas G.; Dietrich, Allen J.; Gregory, Kimberly D.; Grossman, David; Isham, George; LeFevre, Michael L.; Leipzig, Rosanne M.; Marion, Lucy N.; Melnyk, Bernadette; Moyer, Virginia A.; Ockene, Judith K.; Sawaya, George F.; Schwartz, J. Sanford; Wilt, Timothy

    2009-01-01

    Description: In 1996, the U. S. Preventive Services Task Force (USPSTF) recommended that all women planning or capable of pregnancy take a multivitamin supplement containing folic acid for the prevention of neural tube defects. This recommendation is an update of the 1996 USPSTF recommendation. Meth

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

    DEFF Research Database (Denmark)

    Papaccio, G; Nicoletti, F; Pisanti, F A;

    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...

  3. Long chain N-3 polyunsaturated fatty acids in the prevention of allergic and cardiovascular disease.

    Science.gov (United States)

    van den Elsen, Lieke; Garssen, Johan; Willemsen, Linette

    2012-01-01

    The diet is considered to have a major impact on human health. Dietary lipids including long chain polyunsaturated fatty acids (LCPUFA) possess potent immunomodulatory activities. Over the last decades the incidence of inflammatory disorders including allergic and cardiovascular diseases (CVD) has been rising. This phenomenon is associated with deficiencies in N-3 LCPUFA, found in fatty fish, and increased content of N-6 LCPUFA in the Western diet. LCPUFA act via different mechanisms including membrane fluidity, raft composition, lipid mediator formation, signaling pathways and transmembrane receptors. N-3 LCPUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce the development of allergic disease by affecting both the innate and adaptive immune system involved in the initiation and persistence of allergic disease. Fish oil has been shown to be effective in the primary prevention of allergic disease in infants at risk when supplemented during pregnancy and lactation. Subtle effects of N-3 LCPUFA on the outcome of the immune response may underlie these protective effects. This review describes the currently reported effects of LCPUFA on dendritic cells, T cells, B cells and mast cells. Also CVD are positively affected by N-3 LCPUFA. Populations consuming high amounts of oily fish are protected against CVD. Moreover N-3 LCPUFA are effective in the secondary prevention of cardiovascular events. Amongst other effects, EPA and DHA have been shown to suppress endothelial cell activation hereby reducing adhesion molecule expression and endothelial cell - leukocyte interactions. This review describes the mechanistic basis of the preventive role for N-3 LCPUFA in allergic disease and CVD.

  4. Omega-3 fatty acids for breast cancer prevention and survivorship.

    Science.gov (United States)

    Fabian, Carol J; Kimler, Bruce F; Hursting, Stephen D

    2015-05-04

    Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case-control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship.

  5. Using vitamin E to prevent the impairment in behavioral test, cell loss and dendrite changes in medial prefrontal cortex induced by tartrazine in rats.

    Science.gov (United States)

    Rafati, Ali; Nourzei, Nasrin; Karbalay-Doust, Saied; Noorafshan, Ali

    2017-03-01

    Tartrazine is a food color that may adversely affect the nervous system. Vitamin E is a neuro-protective agent. This study aimed to evaluate the effects of tartrazine and vitamin E on the performance of rats in memory and learning tests as well as the structure of medial Prefrontal Cortex (mPFC). The rats were first divided into seven groups which received the followings for a period of seven weeks: distilled water, corn oil, vitamin E (100mg/kg/day), a low dose (50mg/kg/day) and a high dose (50mg/kg/day) of tartrazine with and without vitamin E. Behavioral tests were conducted and the brain was extracted for stereological methods The high dose of tartrazine decreased the exploration time of novel objects (PE plus tartrazine prevented the above-mentioned changes. An acceptable daily dose of tartrazine could induce impairment in spatial memory and dendrite structure. Moreover, a high dose of tartrazine may defect the visual memory, mPFC structure, the spatial memory and also cause dendrite changes. Vitamin E could prevent the behavioral and structural changes.

  6. Critical rate of electrolyte circulation for preventing zinc dendrite formation in a zinc-bromine redox flow battery

    Science.gov (United States)

    Yang, Hyeon Sun; Park, Jong Ho; Ra, Ho Won; Jin, Chang-Soo; Yang, Jung Hoon

    2016-09-01

    In a zinc-bromine redox flow battery, a nonaqueous and dense polybromide phase formed because of bromide oxidation in the positive electrolyte during charging. This formation led to complicated two-phase flow on the electrode surface. The polybromide and aqueous phases led to different kinetics of the Br/Br- redox reaction; poor mixing of the two phases caused uneven redox kinetics on the electrode surface. As the Br/Br- redox reaction was coupled with the zinc deposition reaction, the uneven redox reaction on the positive electrode was accompanied by nonuniform zinc deposition and zinc dendrite formation, which degraded battery stability. A single-flow cell was operated at varying electrolyte circulation rates and current densities. Zinc dendrite formation was observed after cell disassembly following charge-discharge testing. In addition, the flow behavior in the positive compartment was observed by using a transparent version of the cell. At low rate of electrolyte circulation, the polybromide phase clearly separated from the aqueous phase and accumulated at the bottom of the flow frame. In the corresponding area on the negative electrode, a large amount of zinc dendrites was observed after charge-discharge testing. Therefore, a minimum circulation rate should be considered to avoid poor mixing of the positive electrolyte.

  7. The role of dendritic cells in the generation of CD4(+) CD25(HI) Foxp3(+) T cells induced by amino acid copolymers.

    Science.gov (United States)

    Kawamoto, Norio; Ohnishi, Hidenori; Kondo, Naomi; Strominger, Jack L

    2013-01-01

    The effects of the amino acid copolymers used in the therapy of experimental autoimmune encephalomyelitis, poly(Y,E,A,K)(n) (Copaxone(®)) and poly(Y,F,A,K)(n), on murine myeloid cells have been investigated. After administration of these copolymers to mice, increases in several splenic myeloid cell populations were observed, including CD11b(+) CD11c(+) dendritic cells. The latter were the major splenic cell type that secreted CCL22 (macrophage-derived chemokine) on stimulation with amino acid copolymers. CCL22 secretion was also stimulated from bone marrow-derived dendritic cells (BMDC) generated with GM-CSF in much larger amounts than from bone marrow-derived macrophages generated with M-CSF. Moreover, CCL22 secretion could also be obtained using BMDC generated from two different types of MHC II(-/-) mice, indicating that an innate immune receptor is involved. Finally, incubation of these BMDC or splenic dendritic cells with naive CD4(+) CD25(-) T cells resulted in formation of CD4(+) CD25(HI) Foxp3 T cells (~25% of which were Foxp3(+)). The number of these regulatory cells was doubled by pretreatment of BMDC with amino acid copolymers.

  8. Impact of lactic Acid bacteria on dendritic cells from allergic patients in an experimental model of intestinal epithelium.

    Science.gov (United States)

    Ratajczak, Céline; Duez, Catherine; Grangette, Corinne; Pochard, Pierre; Tonnel, André-Bernard; Pestel, Joël

    2007-01-01

    Lactic acid bacteria (LAB) are Gram positive nonpathogenic commensal organisms present in human gastrointestinal tract. In vivo, LAB are separated from antigen-presenting cells such as dendritic cells (DC) by the intestinal epithelial barrier. In this study, the impact of one LAB strain (Lactobacillus casei ATCC393) on human monocyte-derived DC from allergic and healthy donors was assessed by using a polarized epithelium model. Confocal and flow cytometer analyses showed that immature DC efficiently captured FITC-labelled L. casei through the epithelial layer. After interaction with L. casei, DC acquired a partial maturation status (i.e., CD86 and CD54 increase) and increased their interleukin (IL)-10 and IL-12 production. Interestingly, after activation by L. casei in the presence of experimental epithelium, DC from allergic patients instructed autologous naïve CD4(+) T cells to produce more interferon-gamma than without the epithelium. Thus by modulating human DC reactivity, LAB and intestinal epithelium might modify T cell immune response and regulate the development of allergic reaction.

  9. Impact of Lactic Acid Bacteria on Dendritic Cells from Allergic Patients in an Experimental Model of Intestinal Epithelium

    Directory of Open Access Journals (Sweden)

    Céline Ratajczak

    2007-01-01

    Full Text Available Lactic acid bacteria (LAB are Gram positive nonpathogenic commensal organisms present in human gastrointestinal tract. In vivo, LAB are separated from antigen-presenting cells such as dendritic cells (DC by the intestinal epithelial barrier. In this study, the impact of one LAB strain (Lactobacillus casei ATCC393 on human monocyte-derived DC from allergic and healthy donors was assessed by using a polarized epithelium model. Confocal and flow cytometer analyses showed that immature DC efficiently captured FITC-labelled L. casei through the epithelial layer. After interaction with L. casei, DC acquired a partial maturation status (i.e., CD86 and CD54 increase and increased their interleukin (IL-10 and IL-12 production. Interestingly, after activation by L. casei in the presence of experimental epithelium, DC from allergic patients instructed autologous naïve CD4+ T cells to produce more interferon-γ than without the epithelium. Thus by modulating human DC reactivity, LAB and intestinal epithelium might modify T cell immune response and regulate the development of allergic reaction.

  10. The effect of caffeic acid phenethyl ester on the functions of human monocyte-derived dendritic cells

    Directory of Open Access Journals (Sweden)

    Wu Wen-Mein

    2009-07-01

    Full Text Available Abstract Background Propolis, an ancient herbal medicine, has been reported the beneficial effect both in asthma patients and murine model of asthma, but the mechanism was not clearly understood. In this study, the effect of caffeic acid phenethyl ester (CAPE, the most extensively studied components in propolis, on the functions of human monocyte-derived dendritic cells (MoDCs was investigated. Results CAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract. CAPE significantly inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs stimulated by crude mite extract. In contrast, the upregulation of costimulatory molecules in mature MoDCs was not suppressed by CAPE. Further, the antigen presenting ability of DCs was not inhibited by CAPE. CAPE inhibited IκBα phosphorylation and NF-κB activation but not mitogen-activated protein kinase (MAPK family phosphorylation in human MoDCs. Conclusion These results indicated that CAPE inhibited cytokine and chemokine production by MoDCs which might be related to the NF-κB signaling pathway. This study provided a new insight into the mechanism of CAPE in immune response and the rationale for propolis in the treatment of asthma and other allergic disorders.

  11. Yeast adaptation to weak acids prevents futile energy expenditure

    NARCIS (Netherlands)

    Ullah, A.; Chandrasekaran, G.; Brul, S.; Smits, G.J.

    2013-01-01

    Weak organic acids (WOAs) are widely used preservatives to prevent fungal spoilage of foods and beverages. Exposure of baker's yeast Saccharomyces cerevisiae to WOA leads to cellular acidification and anion accumulation. Pre-adaptation of cultures reduced the rate of acidification caused by weak aci

  12. Human Gastric Epithelial Cells Contribute to Gastric Immune Regulation by Providing Retinoic Acid to Dendritic Cells

    OpenAIRE

    Bimczok, Diane; John Y. Kao; Zhang, Min; Cochrun, Steven; Mannon, Peter; Peter, Shajan; Wilcox, Charles M.; Mönkemüller, Klaus E; Harris, Paul R.; Grams, Jayleen M.; Stahl, Richard D.; Smith, Phillip D.; Smythies, Lesley E.

    2014-01-01

    Despite the high prevalence of chronic gastritis caused by H. pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule, retinol, and that gastric epithelial cells express both RA biosynthesis genes and RA res...

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

    DEFF Research Database (Denmark)

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

    DEFF Research Database (Denmark)

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

    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...... 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 cells were...... incubated with 10 microg/ml UV-inactivated bacteria or 10 microg/ml phytohemagglutinin (PHA) for four days. Proliferation was assessed by incorporation of radioactive thymidine into NK cell DNA. The IFN-gamma concentration was measured by ELISA. Incubation of NK cells with a Lactobacillus acidophilus strain...

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

    Directory of Open Access Journals (Sweden)

    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. Yeast adaptation to weak acids prevents futile energy expenditure

    Directory of Open Access Journals (Sweden)

    Azmat eUllah

    2013-06-01

    Full Text Available Weak organic acids (WOA are widely used preservatives to prevent fungal spoilage of foods and beverages. Exposure of baker’s yeast Saccharomyces cerevisiae to WOA leads to cellular acidification and anion accumulation. Pre-adaptation of cultures reduced the rate of acidification caused by weak acid exposure, most likely as a result of changes in plasma membrane or cell wall composition. In order to adapt to sublethal concentrations of the acids and grow, yeast cells activate ATP consuming membrane transporters to remove protons and anions. We explored to what extent ATP depletion contributes to growth inhibition in sorbic or acetic acid treated cells. Therefore, we analyzed the effect of the reduction of proton and anion pumping activity on intracellular pH (pHi, growth, and energy status upon exposure to the hydrophilic acetic acid (HA and the lipophilic sorbic acid (HS. ATP concentrations were dependent on the severity of the stress. Unexpectedly, we observed a stronger reduction of ATP with growth reducing than with growth inhibitory concentrations of both acids. We deduce that the not the ATP reduction caused by proton pumping, but rather the cost of sorbate anion pumping contributes to growth inhibition. A reduction of proton pumping activity may reduce ATP consumption, but the resulting decrease of intracellular pH affects growth more. ATP utilization was differentially regulated during moderate and severe stress conditions. We propose that the energy depletion alone is not the cause of growth inhibition during HA or HS stress. Rather, the cells appear to reduce ATP consumption in high stress conditions, likely to prevent futile cycling and maintain energy reserves for growth resumption in more favorable conditions. The mechanism for such decision making remains to be established.

  17. Reactive oxygen species are involved in BMP-induced dendritic growth in cultured rat sympathetic neurons.

    Science.gov (United States)

    Chandrasekaran, Vidya; Lea, Charlotte; Sosa, Jose Carlo; Higgins, Dennis; Lein, Pamela J

    2015-07-01

    Previous studies have shown that bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, the downstream signaling molecules that mediate the dendrite promoting activity of BMPs are not well characterized. Here we test the hypothesis that reactive oxygen species (ROS)-mediated signaling links BMP receptor activation to dendritic growth. In cultured rat sympathetic neurons, exposure to any of the three mechanistically distinct antioxidants, diphenylene iodinium (DPI), nordihydroguaiaretic acid (NGA) or desferroxamine (DFO), blocked de novo BMP-induced dendritic growth. Addition of DPI to cultures previously induced with BMP to extend dendrites caused dendritic retraction while DFO and NGA prevented further growth of dendrites. The inhibition of the dendrite promoting activity of BMPs by antioxidants was concentration-dependent and occurred without altering axonal growth or neuronal cell survival. Antioxidant treatment did not block BMP activation of SMAD 1,5 as determined by nuclear localization of these SMADs. While BMP treatment did not cause a detectable increase in intracellular ROS in cultured sympathetic neurons as assessed using fluorescent indicator dyes, BMP treatment increased the oxygen consumption rate in cultured sympathetic neurons as determined using the Seahorse XF24 Analyzer, suggesting increased mitochondrial activity. In addition, BMPs upregulated expression of NADPH oxidase 2 (NOX2) and either pharmacological inhibition or siRNA knockdown of NOX2 significantly decreased BMP-7 induced dendritic growth. Collectively, these data support the hypothesis that ROS are involved in the downstream signaling events that mediate BMP7-induced dendritic growth in sympathetic neurons, and suggest that ROS-mediated signaling positively modulates dendritic complexity in peripheral neurons.

  18. [Folic acid: Primary prevention of neural tube defects. Literature Review].

    Science.gov (United States)

    Llamas Centeno, M J; Miguélez Lago, C

    2016-03-01

    Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects.

  19. Lauric acid and myristic acid prevent testosterone induced prostatic hyperplasia in rats.

    Science.gov (United States)

    Veeresh Babu, S V; Veeresh, B; Patil, Anup A; Warke, Y B

    2010-01-25

    Numerous plants have proven to improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with benign prostatic hyperplasia. Major components of those plants were lauric acid and myristic acid. Our study investigated whether lauric acid or myristic acid prevent testosterone induced prostatic hyperplasia in rats. Rats were divided into negative control and testosterone induced prostatic hyperplasia rats (positive control, low dose lauric acid treated, high dose lauric acid treated, low dose of myristic acid treated, high dose of myristic acid treated, finasteride treated). Testosterone and drug treatment were carried out for 14 days. Body weights were recorded before and after treatment. On 15th day, rats were sacrificed, prostates were weighed and histopathological studies were carried out. Lauric acid/myristic acid treatment showed significant inhibition of prostate enlargement and protection of histoarchitecture of prostate when compared with positive control group. In conclusion, the study showed that lauric acid/myristic acid reduced the increase of both prostate weight and prostate weight:body weight ratio, markers of testosterone induced prostatic hyperplasia in rats.

  20. [Inflammatory dendritic cells].

    Science.gov (United States)

    Segura, Elodie; Amigorena, Sebastian

    2014-01-01

    Dendritic cells are a rare and heterogeneous population of professional antigen-presenting cells. Several murine dendritic cell subpopulations have been identified that differ in their phenotype and functional properties. In the steady state, committed dendritic cell precursors differentiate into lymphoid organ-resident dendritic cells and migratory tissue dendritic cells. During inflammation appears an additional dendritic cell subpopulation that has been termed « inflammatory dendritic cells ». Inflammatory dendritic cells differentiate in situ from monocytes recruited to the site of inflammation. Here, we discuss how mouse inflammatory dendritic cells differ from macrophages and from other dendritic cell populations. Finally, we review recent work on human inflammatory dendritic cells.

  1. Tolerogenic interactions between CD8+ dendritic cells and NKT cells prevent rejection of bone marrow and organ grafts.

    Science.gov (United States)

    Hongo, David; Tang, Xiaobin; Zhang, Xiangyue; Engleman, Edgar G; Strober, Samuel

    2017-01-17

    The combination of total lymphoid irradiation and anti-T cell antibodies safely induces immune tolerance to combined hematopoietic cell and organ allografts in humans. Our mouse model required host natural killer T (NKT) cells to induce tolerance. Since NKT cells normally depend on signals from CD8+ dendritic cells (DCs) for their activation, we used the mouse model to test the hypothesis that after lymphoid irradiation host CD8+DCs play a requisite role in tolerance induction through interactions with NKT cells. Selective deficiency of either CD8+DCs or NKT cells abrogated chimerism and organ graft acceptance. After radiation, the CD8+DCs increased expression of surface molecules required for NKT and apoptotic cell interactions and developed suppressive immune functions including production of indoleamine 2,3-deoxygenase (IDO). Injection of naïve mice with apoptotic spleen cells generated by irradiation led to DC changes similar to those induced by lymphoid radiation, suggesting that apoptotic body ingestion by CD8+DCs initiates tolerance induction. Tolerogenic CD8+DCs induced the development of tolerogenic NKT cells with a marked Th2 bias that, in turn, regulated the differentiation of the DCs and suppressed rejection of the transplants. Thus, reciprocal interactions between CD8+DCs and iNKT cells are required for tolerance induction in this system that was translated into a successful clinical protocol.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Science.gov (United States)

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

    2011-06-01

    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 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

  5. Folic acid and primary prevention of birth defects.

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Chan, Ben Chung Lap; Li, Long Fei; Hu, Shui Qing; Wat, Elaine; Wong, Eric Chun Wai; Zhang, Vanilla Xin; Lau, Clara Bik San; Wong, Chun Kwok; Hon, Kam Lun Ellis; Hui, Patrick Chi Leung; Leung, Ping Chung

    2015-09-10

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Gene expression analysis of dendritic cells that prevent diabetes in NOD mice: analysis of chemokines and costimulatory molecules.

    NARCIS (Netherlands)

    Morel, P.A.; Srinivas, M.; Turner, M.S.; Fuschiotti, P.; Munshi, R.; Bahar, I.; Feili-Hariri, M.; Ahrens, E.T.

    2011-01-01

    We have demonstrated previously that BM-derived DCs can prevent diabetes development and halt progression of insulitis in NOD mice, the mouse model of type 1 diabetes. The DC population that was most effective in this therapy had a mature phenotype, expressed high levels of costimulatory molecules,

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

    Directory of Open Access Journals (Sweden)

    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

  12. Zoledronic acid for prevention and treatment of osteoporosis.

    Science.gov (United States)

    Recknor, Chris

    2011-04-01

    Osteoporosis (OP) is associated with a high risk of fracture and disability and with substantial medical costs. This paper is a review of the intravenous (i.v.) bisphosphonate zoledronic acid 5 mg (ZOL), used in the treatment and prevention of OP. This is a review of the scientific literature, between 2003 and 2010, on the use of ZOL in patients with low bone mass or OP. ZOL, given as a single infusion once yearly, has proven efficacy in reducing risk of vertebral and hip fractures in postmenopausal women with OP. In men and women with a recent hip fracture, ZOL has been shown to reduce the incidence of future clinical fractures. Data also demonstrate an increase in bone mineral density in postmenopausal women with osteopenia, in men with OP, and in patients at risk for glucocorticoid-induced osteoporosis. The ZOL clinical program has shown this agent to be safe and generally well tolerated. Acute flu-like symptoms may occur following the first infusion of ZOL, but these are generally mild and transient, and decrease in frequency with subsequent infusions. Patients must have adequate renal function (creatinine clearance ≥ 35 ml/min) and be adequately hydrated prior to infusion. With orally administered bisphosphonates, patient compliance and persistence with weekly or monthly dosing are frequently suboptimal. The ability to administer i.v. ZOL once yearly over 15 min for the treatment of OP provides the advantage of guaranteeing medication compliance for the duration of the dosing interval.

  13. Cross-linked hyaluronic acid in pressure ulcer prevention.

    Science.gov (United States)

    Beniamino, P; Vadalà, M; Laurino, C

    2016-07-02

    Long-term bedridden patients are at high risk of acquring pressure ulcers (PUs). In this group of patients, prevention is necessary to cut the health costs, improve quality of life and reduce the mortality. Here, we evaluated the effectiveness of a cross-linked hyaluronic acid (HA) as plastic bulking-agent filling and remodelling the deep dermis and subcutaneous space of the skin areas exposed to the risk of necrosis. Our work hypothesis has been to inflate a sub-dermal elastic cushion, filled with a natural ECM component, with the aim to induce a stronger tissue background resistant to the ulcerative process. All the patients had an increased risk of PUs, at the sacral, ileum or heel skin. Patients were being nursed accordingly to the standard orthopaedic ward management with a pressure relieveing air mattress. The standard protocol consisted in body mobilisation every 3 hours, 24 hours a day and accurate cleaning of the skin with liquid soap and water without any towel friction and without adding any cream or lotion for the skin protection. Our filling protocol enclosed: accurate disinfection of the skin to be injected with povidone-iodine solution, followed by a local anaesthesia with 28G 13 mm needle, injecting 1.5 ml of 1% xylocaine. Then slow, deep, subcutaneous injection of cross-linked HA was performed with a 18G long needle, in order to deliver a homogeneous, soft gel layer underneath and around the whitish erythematous skin edges at risk of ulceration. Patients' tolerability of the compound and adverse events were also recorded. There were 15 patients (78-94 years old) who participated in the study. All tolerated the procedure very well and no serious side effects were declared. No skin pressure ulceration was detected in the four weeks follow-up Conclusion: We have demonstrated the safety and tolerability of a cross-linked HA subdermal injection in PUs prevention. The compound stratifies in a soft, elastic, interstitial bulk into the deep dermis, thus

  14. Use of organic acids for prevention and removal of Bacillus subtilis biofilms on food contact surfaces.

    Science.gov (United States)

    Akbas, Meltem Yesilcimen; Cag, Seyda

    2016-10-01

    The efficacies of organic acid (citric, malic, and gallic acids) treatments at 1% and 2% concentrations on prevention and removal of Bacillus subtilis biofilms were investigated in this study. The analyses were conducted on microtitration plates and stainless steel coupons. The biofilm removal activities of these organic acids were compared with chlorine on both surfaces. The results showed that citric acid treatments were as powerful as chlorine treatments for prevention and removal of biofilms. The antibiofilm effects of malic acid treatments were higher than gallic acid and less than citric acid treatment. When the antibiofilm effects of these acids and chlorine on the two surfaces were compared, the prevention and removal of biofilms were measured higher on microtitration plates than those on stainless steel coupons. Higher reductions were obtained by increasing concentrations of sanitizers on 24-hour biofilm with 20-minute sanitizer treatments for removal of biofilms.

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

    Science.gov (United States)

    Brix, Susanne; Lund, Pia; Kjaer, Tanja M R; Straarup, Ellen M; Hellgren, Lars I; Frøkiaer, Hanne

    2010-03-01

    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 provided by dendritic cells (DCs). Upon interaction with DCs primed by different concentrations and species of gut bacteria, CD4(+) T cells were activated according to the type of DC stimulus. The levels of CD80 were found to correlate to the levels of expression of CD28 and to the proliferation of CD4(+) T cells, while the presence of CD40 and CD86 on DCs inversely affected inducible costimulator (ICOS) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in CD4(+) T cells. For all DC stimuli, cells high in n-3 PUFAs showed reduced ability to respond to CD28 stimulation, to proliferate, and to express ICOS and CTLA-4. Diminished T-cell receptor (TCR) and CD28 signalling was found to be responsible for n-3 PUFA effects. Thus, the dietary fatty acid composition influences the overall level of CD4(+) T-cell activation induced by DCs, while the priming effect of the DC stimuli modulates CD80, CD86 and CD40 levels, thereby affecting and shaping activation of acquired immunity by differential regulation of proliferation and costimulatory molecule expression in CD4(+) T cells.

  16. Involvement of suppressive B-lymphocytes in the mechanism of tolerogenic dendritic cell reversal of type 1 diabetes in NOD mice.

    Science.gov (United States)

    Di Caro, Valentina; Phillips, Brett; Engman, Carl; Harnaha, Jo; Trucco, Massimo; Giannoukakis, Nick

    2014-01-01

    The objective of the study was to identify immune cell populations, in addition to Foxp3+ T-regulatory cells, that participate in the mechanisms of action of tolerogenic dendritic cells shown to prevent and reverse type 1 diabetes in the Non-Obese Diabetic (NOD) mouse strain. Co-culture experiments using tolerogenic dendritic cells and B-cells from NOD as well as transgenic interleukin-10 promoter-reporter mice along with transfer of tolerogenic dendritic cells and CD19+ B-cells into NOD and transgenic mice, showed that these dendritic cells increased the frequency and numbers of interleukin-10-expressing B-cells in vitro and in vivo. The expansion of these cells was a consequence of both the proliferation of pre-existing interleukin-10-expressing B-lymphocytes and the conversion of CD19+ B-lymphcytes into interleukin-10-expressing cells. The tolerogenic dendritic cells did not affect the suppressive activity of these B-cells. Furthermore, we discovered that the suppressive murine B-lymphocytes expressed receptors for retinoic acid which is produced by the tolerogenic dendritic cells. These data assist in identifying the nature of the B-cell population increased in response to the tolerogenic dendritic cells in a clinical trial and also validate very recent findings demonstrating a mechanistic link between human tolerogenic dendritic cells and immunosuppressive regulatory B-cells.

  17. Involvement of suppressive B-lymphocytes in the mechanism of tolerogenic dendritic cell reversal of type 1 diabetes in NOD mice.

    Directory of Open Access Journals (Sweden)

    Valentina Di Caro

    Full Text Available The objective of the study was to identify immune cell populations, in addition to Foxp3+ T-regulatory cells, that participate in the mechanisms of action of tolerogenic dendritic cells shown to prevent and reverse type 1 diabetes in the Non-Obese Diabetic (NOD mouse strain. Co-culture experiments using tolerogenic dendritic cells and B-cells from NOD as well as transgenic interleukin-10 promoter-reporter mice along with transfer of tolerogenic dendritic cells and CD19+ B-cells into NOD and transgenic mice, showed that these dendritic cells increased the frequency and numbers of interleukin-10-expressing B-cells in vitro and in vivo. The expansion of these cells was a consequence of both the proliferation of pre-existing interleukin-10-expressing B-lymphocytes and the conversion of CD19+ B-lymphcytes into interleukin-10-expressing cells. The tolerogenic dendritic cells did not affect the suppressive activity of these B-cells. Furthermore, we discovered that the suppressive murine B-lymphocytes expressed receptors for retinoic acid which is produced by the tolerogenic dendritic cells. These data assist in identifying the nature of the B-cell population increased in response to the tolerogenic dendritic cells in a clinical trial and also validate very recent findings demonstrating a mechanistic link between human tolerogenic dendritic cells and immunosuppressive regulatory B-cells.

  18. MCS-18, a natural product isolated from Helleborus purpurascens, inhibits maturation of dendritic cells in ApoE-deficient mice and prevents early atherosclerosis progression.

    Science.gov (United States)

    Dietel, Barbara; Muench, Rabea; Kuehn, Constanze; Kerek, Franz; Steinkasserer, Alexander; Achenbach, Stephan; Garlichs, Christoph D; Zinser, Elisabeth

    2014-08-01

    Inflammation accelerates both plaque progression and instability in the pathogenesis of atherosclerosis. The inhibition of dendritic cell (DC) maturation is a promising approach to suppress excessive inflammatory immune responses and has been shown to be protective in several autoimmune models. The aim of this study was to investigate the immune modulatory effects of the natural substance MCS-18, an inhibitor of DC maturation, regarding the progression of atherosclerosis in ApoE-deficient mice. ApoE-deficient mice were fed for twelve weeks with a Western-type diet (n = 32) or normal chow (control group; n = 16). Animals receiving high-fat diet were treated with MCS-18 (500 μg/kg body weight, n = 16) or saline (n = 16) twice a week. After 12 weeks, animals were transcardially perfused and sacrificed. The percentage of mature DCs (CD3(-)/CD19(-)/CD14(-)/NK1.1(-)/CD11c(+)/MHCII(+)/CD83(+)/CD86(+)) and T cell subpopulations (CD4(+)/CD25(+)/Foxp3(+), CD3/CD4/CD8) was analyzed in peripheral blood and in the spleen using flow cytometry. Plaque size was determined in the aortic root and the thoracoabdominal aorta using en-face staining. Immunohistochemical stainings served to detect inflammatory cells in the aortic root. Several cytokines and chemokines were determined in serum using multiplex assays. In splenic cells derived from saline-treated atherosclerotic mice an increased DC maturation, reflected by the upregulation of CD83 and CD86 expression, was observed. The enhanced expression of both maturation markers was absent in MCS-18 treated atherosclerotic mice. While the percentage of splenic Foxp3 expressing Treg was increased in animals receiving MCS-18 compared to saline-treated atherosclerotic mice, cytotoxic T cells were reduced in the spleen and in atherosclerotic lesions of the aortic root. Furthermore, proatherogenic cytokines (e.g. IL-6 and IFN-γ) and chemokines (e.g. MIP-1β) were decreased in serum of MCS-18-treated animals when compared to saline

  19. Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons.

    Science.gov (United States)

    Vila-Luna, S; Cabrera-Isidoro, S; Vila-Luna, L; Juárez-Díaz, I; Bata-García, J L; Alvarez-Cervera, F J; Zapata-Vázquez, R E; Arankowsky-Sandoval, G; Heredia-López, F; Flores, G; Góngora-Alfaro, J L

    2012-01-27

    Chronic caffeine consumption has been inversely associated with the risk of developing dementia and Alzheimer's disease. Here we assessed whether chronic caffeine treatment prevents the behavioral and cognitive decline that male Wistar rats experience from young (≈3 months) to middle age (≈10 months). When animals were young they were evaluated at weekly intervals in three tests: motor activity habituation in the open field (30-min sessions at the same time on consecutive days), continuous spontaneous alternation in the Y-maze (8 min), and elevated plus-maze (5 min). Afterward, rats from the same litter were randomly assigned either to a caffeine-treated group (n=13) or a control group (n=11), which received only tap water. Caffeine treatment (5 mg/kg/day) began when animals were ≈4 months old, and lasted for 6 months. Behavioral tests were repeated from day 14 to day 28 after caffeine withdrawal, a time period that is far in excess for the full excretion of a caffeine dose in this species. Thirty days after caffeine discontinuation brains were processed for Golgi-Cox staining. Compared with controls, we found that middle-aged rats that had chronically consumed low doses of caffeine (1) maintained their locomotor habituation during the second consecutive day exposure to the open field (an index of non-associative learning), (2) maintained their exploratory drive to complete the conventional minimum of nine arm visits required to calculate the alternation performance in the Y-maze in a greater proportion, (3) maintained their alternation percentage above chance level (an index of working memory), and (4) did not increase the anxiety indexes assessed by measuring the time spent in the open arms of the elevated plus maze. In addition, morphometric analysis of hippocampal neurons revealed that dendritic branching (90-140 μm from the soma), length of 4th and 5th order branches, total dendritic length, and spine density in distal dendritic branches were greater in

  20. Deficiency of a Disintegrin and Metalloproteinase 10 (ADAM10) on dendritic cells prevents the development of type 2 immunity and IgE production

    Science.gov (United States)

    Mice in which dendritic cells (DCs)lack ADAM10 (ADAM10DC-/-) were found to have a dramatic decrease in TH2 immunity and IgE production, as measured by both lung inflammation to house dust mite (HDM) and active systemic anaphylaxis models (ASA). With HDM, the ADAM10DC-/- had significantly less airway...

  1. Prevention of spina bifida: folic acid intake during pregnancy in Gulu district, northern Uganda.

    Science.gov (United States)

    Bannink, Femke; Larok, Rita; Kirabira, Peter; Bauwens, Lieven; van Hove, Geert

    2015-01-01

    The intake of folic acid before conception and during the first trimester of pregnancy can prevent spina bifida. This paper describes folic acid intake in women in Gulu district in northern Uganda. Structured interviews were held with 394 women attending antenatal care (ANC), 15 mothers of children with spina bifida, and 35 health workers in 2012 and 2013. SPSS16 was used for data analysis. 1/4 mothers of children with spina bifida took folic acid during late pregnancy, none preconception. None had knowledge about folic acid and spina bifida prevention. 33.5% of women attending ANC had ever heard about spina bifida, 1% knew folic acid intake can prevent spina bifida. 42.4% took folic acid supplements in late pregnancy, 8.1% during the first trimester, none preconception. All women said to have eaten food rich in folic acid. None were aware about fortified foods. 7% of health workers understood the importance of early folic acid intake. All health workers recommended folic acid intake to women attending ANC. 20% of the health workers and 25% of the women said folic acid supplements are not always available. Folic acid intake is limited in northern Uganda. This is attributed to limited education and understanding of women and health workers about the importance of early folic acid intake, late presentation of women at ANC, poor supply chain and dilapidated health services caused by war and poverty. A combination of food fortification, sensitization of health workers, women, and improving folic acid supply is recommended.

  2. Omega-3 Fatty Acids and Primary and Secondary Prevention of Cardiovascular Disease.

    Science.gov (United States)

    Cao, Yong; Lu, Lei; Liang, Jun; Liu, Min; Li, Xianchi; Sun, RongRong; Zheng, Yi; Zhang, Peiying

    2015-05-01

    The prevalence of cardiovascular disease (CVD) is increasing dramatically especially in developing countries like India. CVD is a leading cause of morbidity and mortality. There has been a growing awareness of the role of nutrients in the prevention of CVD. One specific recommendation in the battle against CVD is the increased intake of omega-3 fatty acids, which are polyunsaturated fatty acids. Studies have reported inverse associations of CVD with dietary intake of omega-3 fatty acids, suggesting that omega-3 fatty acids supplementation might exert protective effects on CVD. They exert their cardioprotective effect through multiple mechanisms. Omega-3 fatty acid therapy has shown promise as a useful tool in the primary and secondary prevention of CVD. This review briefly summarizes the effects of omega-3 fatty acids in primary and secondary prevention of CVD.

  3. Secondary prevention with folic acid : Effects on clinical outcomes

    NARCIS (Netherlands)

    Liem, A; Reynierse-Buitenwerf, GH; Zwinderman, AH; Jukema, JW; van Veldhuisen, DJ

    2003-01-01

    OBJECTIVES We sought to conduct a randomized trial with folic acid 0.5 mg/day in a patient population with stable coronary artery disease (CAD). BACKGROUND Folic acid has favorable effects on vascular endothelium and lowers plasma homocysteine levels. In addition, homocysteine appears to be an indep

  4. Generation of functionally mature dendritic cells from elutriated monocytes using polyinosinic : polycytidylic acid and soluble CD40 ligand for clinical application.

    Science.gov (United States)

    Kim, S; Kim, H O; Kim, H J; Lee, K; Kim, H-S

    2008-12-01

    Despite the increasing use of dendritic cell (DC) vaccination in clinical trials, optimal conditions for the generation of functionally mature DCs remain to be established. The current standard DC maturation protocol for clinical trials has been used as an inflammatory cytokine cocktail [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and prostaglandin E(2)], but this cocktail induced insufficient maturation of DCs derived from elutriated monocytes when cultured in X-VIVO 15. The aim of this study was to define effective combinations of stimulators for generating functionally mature DCs from elutriated monocytes under current good manufacturing practice conditions. We compared the functional capacity of DCs in response to all possible pairwise combinations of four different classes of stimuli: TNF-alpha, peptidoglycan, polyinosinic : polycytidylic acid [poly(I:C)] and soluble CD40 ligand (CD40L). Maturation status of DCs stimulated with combination of four stimuli was similar to that of the cytokine cocktail as assessed by the cell surface phenotype. However, only the combination of poly(I:C) + CD40L induced complete functional activation of the whole DC population, assessing IL-12p70 production, allostimulatory activity, migratory response to CCL19 and T helper 1-polarizing capacity. Thus, the protocol based on the combination of poly(I:C) and CD40L is more effective for the induction of clinical-grade DCs from elutriated monocytes than the standard cytokine cocktail.

  5. Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Chen-Chen Lee

    2015-01-01

    Full Text Available This study investigated the immunomodulatory effects of ferulic acid (FA on antigen-presenting dendritic cells (DCs in vitro and its antiallergic effects against ovalbumin- (OVA- induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS stimulation induced a high level of interleukin- (IL- 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF- α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4, MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13, and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN- γ production in bronchoalveolar lavage fluid (BALF and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model.

  6. Postbiotic Modulation of Retinoic Acid Imprinted Mucosal-like Dendritic Cells by Probiotic Lactobacillus reuteri 17938 In Vitro

    OpenAIRE

    2016-01-01

    Lactobacilli are widely used as probiotics with beneficial effects on infection-associated diarrhea, but also used in clinical trials of e.g., necrotizing enterocolitis and inflammatory bowel diseases. The possibility of using probiotic metabolic products, so-called postbiotics, is desirable as it could prevent possible side effects of live bacteria in individuals with a disturbed gut epithelial barrier. Here, we studied how Lactobacillus reuteri DSM 17938 cell-free supernatant (L. reuteri-CF...

  7. Prevention of Sports Injuries by Marine Omega-3 Fatty Acids.

    Science.gov (United States)

    Bryhn, Morten

    2015-01-01

    Sport injuries are common and costly for the professional athlete, the "weekend warrior," and the community. Acute injuries are treated according to current guidelines with the aim of bringing the athlete back into the arena. These guidelines have not taken into account new scientific results of the inflammatory process following a trauma. The 4 hallmarks of inflammation, namely, pain, swelling, redness, and heat, are results of an adequate inflammatory response with the aim of bringing the affected tissue back to restitution (Latin: restitutio ad integrum). Cooling of the affected limb and anti-inflammatory drugs are widely used but may deter healing. The healing process is governed by fatty acids of the omega-3 and omega-6 series. In order to facilitate healing, these fatty acids have to be present in significant amounts in the affected tissues before the trauma occurs. This is particularly relevant for marine omega-3 fatty acids, which are often running low due to insignificant intake of seafood, common in individuals practicing sports. High-energy sports often lead to head and brain trauma. Continuous head traumata may even result in later mental defects. Saturation of brain cells with omega-3 fatty acids, in particular docosahexaenoic acid (DHA), may facilitate healing after brain trauma, thereby counteracting negative long-term results. The present understanding of a normal inflammatory process leading to restitution will be discussed along with data from recent scientific trials.

  8. The confusion about dietary fatty acids recommendations for CHD prevention

    NARCIS (Netherlands)

    Kromhout, D.; Geleijnse, J.M.; Menotti, A.; Jacobs, D.R.

    2011-01-01

    A recent meta-analysis of prospective cohort studies has not found an association between dietary saturated fat intake and CHD incidence. This funnelled the discussion about the importance of the recommendation to lower the intake of saturated fat for the prevention of CHD. At the same time a

  9. The confusion about dietary fatty acids recommendations for CHD prevention

    NARCIS (Netherlands)

    Kromhout, D.; Geleijnse, J.M.; Menotti, A.; Jacobs, D.R.

    2011-01-01

    A recent meta-analysis of prospective cohort studies has not found an association between dietary saturated fat intake and CHD incidence. This funnelled the discussion about the importance of the recommendation to lower the intake of saturated fat for the prevention of CHD. At the same time a docume

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

    Science.gov (United States)

    Ward, M; Hutton, J; Mc Donnell, R; Bachir, N; Scallan, E; O'Leary, M; Hoey, J; Doyle, A; Delany, V; Sayers, G

    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: pfolic acid can prevent NTD also rose from 21% to 66% (c2 test for trend: pfolic acid during pregnancy increased from 14% to 83% from 1996 to 2002 (c2 test for trend: pawareness 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.

  11. A 2015 global update on folic acid-preventable spina bifida and anencephaly.

    Science.gov (United States)

    Arth, Annelise; Kancherla, Vijaya; Pachón, Helena; Zimmerman, Sarah; Johnson, Quentin; Oakley, Godfrey P

    2016-07-01

    Spina bifida and anencephaly are two major neural tube defects. They contribute substantially to perinatal, neonatal, infant, and under-five mortality and life-long disability. To monitor the progress toward the total prevention of folic acid-preventable spina bifida and anencephaly (FAP SBA), we examined their global status in 2015. Based on existing data, we modeled the proportion of FAP SBA that are prevented in the year 2015 through mandatory folic acid fortification globally. We included only those countries with mandatory fortification that added at least 1.0 ppm folic acid as a fortificant to wheat and maize flour, and had complete information on coverage. Our model assumed mandatory folic acid fortification at 200 μg/day is fully protective against FAP SBA, and reduces the rate of spina bifida and anencephaly to a minimum of 0.5 per 1000 births. Our estimates show that, in 2015, 13.2% (35,500 of approximately 268,700 global cases) of FAP SBA were prevented in 58 countries through mandatory folic acid fortification of wheat and maize flour. Most countries in Europe, Africa, and Asia were not implementing mandatory fortification with folic acid. Knowledge that folic acid prevents spina bifida and anencephaly has existed for 25 years, yet only a small fraction of FAP SBA is being prevented worldwide. Several countries still have 5- to 20-fold epidemics of FAP SBA. Implementation of mandatory fortification with folic acid offers governments a proven and rapid way to prevent FAP SBA-associated disability and mortality, and to help achieve health-related Sustainable Development Goals. Birth Defects Research (Part A) 106:520-529, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Prevention of spina bifida: folic acid intake during pregnancy in Gulu district, northern Uganda

    OpenAIRE

    Bannink, Femke; Larok, Rita; Karibari, Peter; Bauwens, Lieven; Van Hove, Geert

    2015-01-01

    Introduction The intake of folic acid before conception and during the first trimester of pregnancy can prevent spina bifida. This paper describes folic acid intake in women in Gulu district in northern Uganda. Methods Structured interviews were held with 394 women attending antenatal care (ANC), 15 mothers of children with spina bifida, and 35 health workers in 2012 and 2013. SPSS16 was used for data analysis. Results 1/4 mothers of children with spina bifida took folic acid during late preg...

  13. [Neural tube defects and folic acid: a historical overview of a highly successful preventive intervention].

    Science.gov (United States)

    Vásquez, Adriana Ordoñez; Suarez-Obando, Fernando

    2015-12-01

    This article gives a broad overview of part of the historical evolution of medical knowledge about neural tube defects (NTD) and the discovery of vitamin B9 or folic acid, as well as some relevant research events that, over the course of several centuries, defined the relationships between the understanding of central nervous system embryology, the discovery of the vitamin, the correlation between folic acid and cell proliferation and lastly the development of preventive measures for this type of defects. This narrative allows us to examine historically relevant concepts underlying clinical actions with a populational impact that prevent NTDs via folic acid consumption prior to conception.

  14. Zoledronic acid infusion for prevention and treatment of osteoporosis

    OpenAIRE

    Sunyecz, John A

    2010-01-01

    John A SunyeczLaurel Highlands Ob/Gyn, Hopwood, Pennsylvania, USA and MenopauseRx, Inc., Uniontown, PA, USAAbstract: Osteoporotic fractures are associated with significant morbidity, reduced quality of life, increased mortality, and high health care costs. Bisphosphonates are standard therapy for treatment of osteoporosis. However, patient compliance and persistence with oral weekly or monthly bisphosphonate therapy are suboptimal and may lead to reduced effectiveness. Zoledronic acid (ZOL) i...

  15. Autologous aldrithiol-2-inactivated HIV-1 combined with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose as a vaccine platform for therapeutic dendritic cell immunotherapy.

    Science.gov (United States)

    Miller, Elizabeth; Spadaccia, Meredith; Sabado, Rachel; Chertova, Elena; Bess, Julian; Trubey, Charles Mac; Holman, Rose Marie; Salazar, Andres; Lifson, Jeffrey; Bhardwaj, Nina

    2015-01-03

    Therapeutic interventions for HIV-1 that successfully augment adaptive immunity to promote killing of infected cells may be a requisite component of strategies to reduce latent cellular reservoirs. Adoptive immunotherapies utilizing autologous monocyte-derived dendritic cells (DCs) that have been activated and antigen loaded ex vivo may serve to circumvent defects in DC function that are present during HIV infection in order to enhance adaptive immune responses. Here we detail the clinical preparation of DCs loaded with autologous aldrithiol-2 (AT-2)-inactivated HIV that have been potently activated with the viral mimic, Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (Poly-ICLC). HIV is first propagated from CD4+ T cells from HIV-infected donors and then rendered non-replicative by chemical inactivation with aldrithiol-2 (AT-2), purified, and quantified. Viral inactivation is confirmed through measurement of Tat-regulated β-galactosidase reporter gene expression following infection of TZM-bl cells. In-process testing for sterility, mycoplasma, LPS, adventitious agents, and removal of AT-2 is performed on viral preparations. Autologous DCs are generated and pulsed with autologous AT-2-inactivated virus and simultaneously stimulated with Poly-ICLC to constitute the final DC vaccine product. Phenotypic identity, maturation, and induction of HIV-specific adaptive immune responses are confirmed via flow cytometric analysis of DCs and cocultured autologous CD4+ and CD8+ T cells. Lot release criteria for the DC vaccine have been defined in accordance with Good Manufacturing Practice (GMP) guidelines. The demonstrated feasibility of this approach has resulted in approval by the FDA for investigational use in antiretroviral (ART) suppressed individuals. We discuss how this optimized DC formulation may enhance the quality of anti-HIV adaptive responses beyond what has been previously observed during DC immunotherapy trials for HIV infection.

  16. Association between activation of phase 2 enzymes and down-regulation of dendritic cell maturation by c9,t11-conjugated linoleic acid.

    Science.gov (United States)

    Bergamo, Paolo; Maurano, Francesco; D'Arienzo, Rossana; David, Chella; Rossi, Mauro

    2008-05-15

    Antioxidant and cytoprotective enzymes (phase 2) exert protective activity against reactive oxygen species (ROS)-induced injury. We have recently shown how the beneficial effects of conjugated linoleic acid (CLA) in a mouse model of an autoimmune disease are parallel with the activation of phase 2 enzymes. In the present study we found that c9,t11-CLA isomer activates cytoprotective enzymes and down-regulates LPS- or gliadin-induced maturation in dendritic cells (DCs) obtained from a murine model of celiac disease. As expected, the enhancement of LPS-induced maturation (increased NFkappaB p65 nuclear translocation, CD86 expression and decreased CD11c+ cell number) was exacerbated by specific glutathione (GSH) inhibitor (buthionine sulphoximine; BSO). Conversely, the down-regulation of DC maturation by antioxidant N-acetylcysteine (NAC) was associated with the marked increase of intracellular thiol concentration. c9,t11-CLA activation of phase 2 enzymes in mouse DCs was observed first. Next, we found that the significant reduction of LPS- and gliadin-induced DC maturation in cultures pre-treated with c9,t11-CLA improved cellular redox status (decreased ROS and higher antioxidant defenses). Finally, the process of DC maturation triggered by gliadin, in contrast with that exhibited by LPS, was not associated with enhanced NFkappaB nuclear translocation and pro-inflammatory cytokines synthesis. These results demonstrate that c9,t11-CLA renders DCs more resistant to gliadin- or LPS-induced maturation, thus indicating that a cytoprotective mechanism elicited by c9,t11-CLA may modulate DC responsiveness.

  17. Characterization of Bone Marrow-Derived Dendritic Cells Developed in Serum-Free Media and their Ability to Prevent Type 1 Diabetes in Nonobese Diabetic Mice

    OpenAIRE

    Looney, Ben M; Chernatynskaya, Anna V.; Clare-Salzler, Michael J.; Xia, Chang-Qing

    2014-01-01

    Dendritic cells (DC) have been investigated as a cell-based therapy for Type 1 Diabetes (T1D). BM-DC expanded ex vivo with GM-CSF and IL-4 is typically cultured with fetal bovine serum (FBS). The effect of FBS on NOD BM-DC has not been extensively studied. In the present study we compare BM-DC generated in serum-free culture media (X-VIVO20; FBS−) with BM-DC generated in media containing 10% FBS (RPMI1640/10%FBS; FBS+). We show that FBS− BM-DC display a phenotype and cytokine-producing profil...

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

    OpenAIRE

    Rahman, Md M; Halade, Ganesh V.; 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...

  19. Fatty acids in treatment and prevention of depression

    Directory of Open Access Journals (Sweden)

    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.

  20. Fish oil prevents essential fatty acid deficiency and enhances growth: clinical and biochemical implications.

    Science.gov (United States)

    Strijbosch, Robert A M; Lee, Sang; Arsenault, Danielle A; Andersson, Charlotte; Gura, Kathleen M; Bistrian, Bruce R; Puder, Mark

    2008-05-01

    Fish oil, a rich source of omega-3 fatty acids, has never been used as the sole source of lipid in clinical practice for fear of development of essential fatty acid deficiency, as it lacks the believed requisite levels of linoleic acid, an omega-6 fatty acid. The objectives of this study were to establish biochemical standards for fish oil as the sole fat and to test the hypothesis that fish oil contains adequate amounts of omega-6 fatty acids to prevent essential fatty acid deficiency. Forty mice were divided into 2 groups that were either pair fed or allowed to eat ad libitum. In each group, 4 subgroups of 5 mice were fed 1%, 5%, and 10% fish oil diets by weight or a control soybean diet for 9 weeks. Blood was collected at 4 time points, and fatty acid analysis was performed. Food intake and weight status were monitored. All groups but the pair-fed 1% fish oil group gained weight, and the 5% fish oil group showed the highest caloric efficiency in both pair-fed and ad libitum groups. Fatty acid profiles for the 1% fish oil group displayed clear essential fatty acid deficiency, 5% fish oil appeared marginal, and 10% and soybean oil diets were found to prevent essential fatty acid deficiency. Fish oil enhances growth through higher caloric efficiency. We established a total omega-6 fatty acid requirement of between 0.30% and 0.56% of dietary energy, approximately half of the conventionally believed 1% as linoleic acid. This can presumably be attributed to the fact that fish oil contains not only a small amount of linoleic acid, but also arachidonic acid, which has greater efficiency to meet omega-6 fatty acid requirements.

  1. Zoledronic acid infusion for prevention and treatment of osteoporosis

    Directory of Open Access Journals (Sweden)

    John A Sunyecz

    2010-10-01

    Full Text Available John A SunyeczLaurel Highlands Ob/Gyn, Hopwood, Pennsylvania, USA and MenopauseRx, Inc., Uniontown, PA, USAAbstract: Osteoporotic fractures are associated with significant morbidity, reduced quality of life, increased mortality, and high health care costs. Bisphosphonates are standard therapy for treatment of osteoporosis. However, patient compliance and persistence with oral weekly or monthly bisphosphonate therapy are suboptimal and may lead to reduced effectiveness. Zoledronic acid (ZOL is an intravenous bisphosphonate that is given once yearly for the treatment of osteoporosis via a medically supervised 15-minute infusion. This ensures compliance for a full 12 months. In clinical trials, an annual infusion of ZOL 5 mg has shown sustained efficacy in reducing hip and spine fractures in postmenopausal women with osteoporosis. It has also been shown to increase bone density in postmenopausal women with osteopenia (low bone mass and in men with osteoporosis. Transient flu-like symptoms are the most common adverse effects following ZOL infusion, and these can generally be managed with acetaminophen. The availability of an intravenous bisphosphonate that ensures compliance over a long dosing interval may help to overcome barriers to efficacy resulting from poor long-term compliance with oral agents.Keywords: fractures, intravenous bisphosphonate, osteoporosis, zoledronic acid

  2. Nucleic Acid Drugs for Prevention of Cardiac Rejection

    Directory of Open Access Journals (Sweden)

    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.

  3. Antibodies to P-selectin glycoprotein ligand-1 block dendritic cell-mediated enterovirus 71 transmission and prevent virus-induced cells death.

    Science.gov (United States)

    Ren, Xiao-Xin; Li, Chuan; Xiong, Si-Dong; Huang, Zhong; Wang, Jian-Hua; Wang, Hai-Bo

    2015-01-01

    P-selectin glycoprotein ligand-1 (PSGL-1) has been proved to serve as the functional receptor for enterovirus 71 (EV71). We found the abundant expression of PSGL-1 on monocyte-derived dendritic cells (MDDCs). However, we have previously demonstrated that MDDCs did not support efficient replication of EV71. Dendritic cells (DCs) have been described to be subverted by various viruses including EV71 for viral dissemination, we thus explore the potential contribution of PSGL-1 on DC-mediated EV71 transmission. We found that the cell-surface-expressing PSGL-1 on MDDCs mediated EV71 binding, and intriguingly, these loaded-viruses on MDDCs could be transferred to encountered target cells; Prior-treatment with PSGL-1 antibodies or interference with PSGL-1 expression diminished MDDC-mediated EV71 transfer and rescued virus-induced cell death. Our data uncover a novel role of PSGL-1 in DC-mediated EV71 spread, and provide an insight into blocking primary EV71 infection.

  4. 基于聚(L-谷氨酸)树状分子的智能药物释放系统研究%DENDRITIC POLY(L-GLUTAMIC ACID) BASED SMART DRUG DELIVERY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    江超; 盛明明; 何斌; 王刚; 吴尧; 顾忠伟

    2011-01-01

    以天然氨基酸L-谷氨酸为原料,通过收敛法合成了聚(L-谷氨酸)树状分子,通过半胱氨酸将抗肿瘤药物甲氨蝶呤( MTX)键合到聚(L-谷氨酸)树状分子上,构建氧化还原敏感的药物传输系统.用核磁(1H~NMR)等对载体以及载药粒子进行了表征.体外释放研究发现,载药粒子具有良好的氧化还原响应性,在不同浓度的还原剂二硫苏糖醇(DTT)作用下药物的释放速率明显不同,当DTT=10 mmol/L时,药物释放较快,DTT=2 mmol/L次之,而DTT=0.2 mmoi/L时无释放现象.体外细胞实验结果表明,聚(L-谷氨酸)树状分子的细胞毒性低,载药粒子对HepG2细胞的增殖有明显的抑制作用.%A redox-sensitive drug delivery system was fabricated. Dendritic poly ( L-glutamic acid) was synthesized. Anti-tumor drug methotrexate ( MTX) was immobilized on the dendritic poly( L-glutamic acid) via disulfide bonds using cystines as linkers. The disulfide bond was sensitive to glutathione in intracellular environment,thus to release the MTX from the dendritic poly ( L-glutamic acid) backbones. The dendritic poly(L-glutamic acid) backbones and drug loaded conjugates were characterized by nuclear magnetic resonance (NMR). The release profiles of the conjugates were investigated in phosphate buffer saline (PBS) with dithiothreitol (DTT) to simulate the intracellular environment; the results showed that the release rates were closely dependant on the concentration of DTT. Higher DTT concentration resulted in faster release. When the DTT concentration was lower than 0. 2 mmol/L, MTX was not released from dendritic backbones. The conjugates were incubated with HepG2 cells to evaluate their anti-tumor effect in vitro. The dendritic poly(L-glutamic acid) was nontoxic to cells even when its concentration was as high as 20 μg/mL. The inhibition effect of the conjugates on tumor cells was better than that of free MTX after incubation for 72 h. Fluorescein isothiocyanate (FITC) was

  5. Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction.

    Science.gov (United States)

    Korkmaz, Sevil; Atmanli, Ayhan; Li, Shiliang; Radovits, Tamás; Hegedűs, Peter; Barnucz, Enikő; Hirschberg, Kristóf; Loganathan, Sivakkanan; Yoshikawa, Yutaka; Yasui, Hiroyuki; Karck, Matthias; Szabó, Gábor

    2015-09-01

    The pathophysiology of ischemic myocardial injury involves cellular events, reactive oxygen species, and an inflammatory reaction cascade. The zinc complex of acetylsalicylic acid (Zn(ASA)2) has been found to possess higher anti-inflammatory and lower ulcerogenic activities than acetylsalicylic acid (ASA). Herein, we studied the effects of both ASA and Zn(ASA)2 against acute myocardial ischemia. Rats were pretreated with ASA (75 mg/kg) or Zn(ASA)2 (100 mg/kg) orally for five consecutive days. Isoproterenol (85 mg/kg, subcutaneously [s.c.]) was applied to produce myocardial infarction. After 17-22 h, animals were anesthetized with sodium pentobarbital (60 mg/kg, intraperitoneally [i.p.]) and both electrical and mechanical parameters of cardiac function were evaluated in vivo. Myocardial histological and gene expression analyses were performed. In isoproterenol-treated rats, Zn(ASA)2 treatment normalized significantly impaired left-ventricular contractility index (Emax 2.6 ± 0.7 mmHg/µL vs. 4.6 ± 0.5 mmHg/µL, P < 0.05), increased stroke volume (30 ± 3 µL vs. 50 ± 6 µL, P < 0.05), decreased systemic vascular resistance (7.2 ± 0.7 mmHg/min/mL vs. 4.2 ± 0.5 mmHg/min/mL, P < 0.05) and reduced inflammatory infiltrate into the myocardial tissues. ECG revealed a restoration of elevated ST-segment (0.21 ± 0.03 mV vs. 0.09 ± 0.02 mV, P < 0.05) and prolonged QT-interval (79.2 ± 3.2 ms vs. 69.5 ± 2.5 ms, P < 0.05) by Zn(ASA)2. ASA treatment did not result in an improvement of these parameters. Additionally, Zn(ASA)2 significantly increased the mRNA-expression of superoxide dismutase 1 (+73 ± 15%), glutathione peroxidase 4 (+44 ± 12%), and transforming growth factor (TGF)-β1 (+102 ± 22%). In conclusion, our data demonstrate that oral administration of zinc and ASA in the form of bis(aspirinato)zinc(II) complex is superior to ASA in preventing electrical

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

    Science.gov (United States)

    Delany, C; McDonnell, R; Robson, M; Corcoran, S; Fitzpatrick, C; De La Harpe, D

    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.

  7. Folic acid for the prevention of neural tube defects: the Danish experience.

    Science.gov (United States)

    Olsen, Sjurdur F; Knudsen, Vibeke Kildegaard

    2008-06-01

    Evidence from controlled trials suggests that ingestion of 0.4 mg of folic acid per day in the periconceptional period is effective in preventing neural tube defects (NTD). For this reason, most countries recommend that women planning pregnancy take folic acid supplements in the periconceptional period, and some countries even fortify stable foods with folic acid. Denmark exemplifies a country with a relatively conservative attitude with respect to taking action in these matters. In 1999, a national information campaign was launched that recommended women planning pregnancy take 0.4 mg of folic acid periconceptionally, but with the moderation that women who eat a healthy diet do not need to take folic acid supplement. The campaign was repeated during 2001. The results of the latter campaign were evaluated by using data from a national survey among pregnant women conducted simultaneously with the campaign by the Danish National Birth Cohort. An increase in the proportion of folic acid users took place concomitantly with the launching of the information events, but the increase was limited. Among women who did not plan their pregnancy, a small proportion had taken folic acid supplements periconceptionally, and this proportion did not change concomitantly with the campaign. Young age and low education were factors associated with low likelihood of taking folic acid. It seems that different and more efficient actions are needed if a more substantial proportion of Danish women and their fetuses are going to benefit from the knowledge that folic acid supplementation in the periconceptional period can prevent NTD.

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

    LENUS (Irish Health Repository)

    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.

  9. Assessment of Turkish women's knowledge concerning folic acid and prevention of birth defects.

    Science.gov (United States)

    Unusan, Nurhan

    2004-10-01

    In Turkey, the incidence of neural tube defects (NTDs) is 30.1 per 10,000 births. For this reason it seems an important problem for women of childbearing age. Adequate periconceptional consumption of folic acid could prevent NTDs. Most women are unaware of this recommendation. The objectives of this study were to evaluate women' knowledge and beliefs with regard to folic acid, and to estimate the consumption frequency of vitamin supplements periconceptionally and during the first trimester of pregnancy. Eight hundred and eighteen married women who had delivered a live-born infant within the previous 12 months completed the questionnaire. Each subject participated in a 20-minute interview, with the questionnaire comprising multiple-choice statements. A random sample of 10 public health centres was drawn from 27 in three districts in Konya where about 50% of the population lives. Only 22% of subjects had heard or read about folic acid. Thirteen per cent of women indicated knowledge of the direct link between folic acid supplementation and NTD prevention. The knowledge was greatest among 26- to 35-year-olds. Women with a university degree were more likely to have heard about folic acid than were less-educated women. The results indicate that further government efforts are needed to inform the population and promote the optimal use of folic acid supplements and folate-enriched foods. It is the responsibility of national authorities to increase health education concerning folic acid and the prevention of NTDs in their countries.

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

    Directory of Open Access Journals (Sweden)

    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

  11. Free dendritic growth

    Science.gov (United States)

    Glicksman, M. E.

    1984-01-01

    Free dendritic growth refers to the unconstrained development of crystals within a supercooled melt, which is the classical 'dendrite problem'. Great strides have been taken in recent years in both the theoretical understanding of dendritic growth and its experimental status. The development of this field will be sketched, showing that transport theory and interfacial thermodynamics (capillarity theory) were sufficient ingredients to develop a truly predictive model of dendrite formation. The convenient, but incorrect, notion of 'maximum velocity' was used for many years to estimate the behavior of dendritic transformations until supplanted by modern dynamic stability theory. The proper combinations of transport theory and morphological stability seem to able to predict the salient aspects of dendritic growth, especially in the neighborhood of the tip. The overall development of cast microstructures, such as equiaxed zone formation, rapidly solidified microstructures, etc., also seems to contain additional non-deterministic features which lie outside the current theories discussed here.

  12. Zoledronic acid infusion for prevention and treatment of osteoporosis.

    Science.gov (United States)

    Sunyecz, John A

    2010-10-14

    Osteoporotic fractures are associated with significant morbidity, reduced quality of life, increased mortality, and high health care costs. Bisphosphonates are standard therapy for treatment of osteoporosis. However, patient compliance and persistence with oral weekly or monthly bisphosphonate therapy are suboptimal and may lead to reduced effectiveness. Zoledronic acid (ZOL) is an intravenous bisphosphonate that is given once yearly for the treatment of osteoporosis via a medically supervised 15-minute infusion. This ensures compliance for a full 12 months. In clinical trials, an annual infusion of ZOL 5 mg has shown sustained efficacy in reducing hip and spine fractures in postmenopausal women with osteoporosis. It has also been shown to increase bone density in postmenopausal women with osteopenia (low bone mass) and in men with osteoporosis. Transient flu-like symptoms are the most common adverse effects following ZOL infusion, and these can generally be managed with acetaminophen. The availability of an intravenous bisphosphonate that ensures compliance over a long dosing interval may help to overcome barriers to efficacy resulting from poor long-term compliance with oral agents.

  13. Techniques to correct and prevent acid mine drainage: A review

    Directory of Open Access Journals (Sweden)

    Santiago Pozo-Antonio

    2014-01-01

    Full Text Available En la actualidad uno de los problemas medioambientales con mayor necesidad de actuación es la contaminación por la formación de drenajes ácidos de mina (AMD: “Acid Mine Drainage” procedentes de estériles de mina. Este es el término utilizado para describir el drenaje generado por la oxidación natural de sulfuros minerales que son expuestos a la acción combinada de agua y oxígeno atmosférico. Los minerales responsables de la generación de AMD son los sulfuros de hierro (pirita, FeS2 y en menor medida la pirrotita, Fe1-XS, los cuales son estables e insolubles mientras no se encuentren en contacto con agua y oxígeno atmosférico. Sin embargo, como consecuencia de la actividad minera, estos dos sulfuros son expuestos a condiciones ambientales oxidantes. La necesidad de prevenir la formación de AMD ha desarrollado numerosas investigaciones sobre los mecanismos de oxidación y su prevención. En el presente trabajo además de realizar una explicación y valoración teórica del proceso de oxidación de la pirita también se realiza un compendio de las medidas preventivas y correctoras más empleadas.

  14. Dendritic polyurea polymers.

    Science.gov (United States)

    Tuerp, David; Bruchmann, Bernd

    2015-01-01

    Dendritic polymers, subsuming dendrimers as well as hyperbranched or highly branched polymers are well established in the field of polymer chemistry. This review article focuses on urea based dendritic polymers and summarizes their synthetic routes through both isocyanate and isocyanate-free processes. Furthermore, this article highlights applications where dendritic polyureas show their specific chemical and physical potential. For these purposes scientific publications as well as patent literature are investigated to generate a comprehensive overview on this topic.

  15. [Folic acid use by pregnant women in Israel for preventing neural tube defects].

    Science.gov (United States)

    Gil, Z; Aran, A; Friedman, O; Beni-Adani, L; Constantini, S

    2000-12-01

    Spina bifida and anencephaly are the most common, serious malformations in neural tube defects (NTD). Randomized trials in the last 2 decades have demonstrated that folic acid, 0.4 mg/d, reduces the incidence of NTD by more than 50%. We investigated the use of folic acid and multivitamins containing folic acid in childbearing women. Of 221 women interviewed, 67 (30%) regularly took pills containing 0.4 mg folic acid. Women with higher educational levels were more likely to take multivitamins with folic acid than were the less educated (p = 0.05). Of the women who took folic acid, only 5 (7.5%) used separate folic acid tablets, before and during their pregnancy. The rest used multivitamins containing folic acid. The 5 women who took folic acid separately were college-educated and nonreligious, and they took multivitamins in addition (p > 0.05). Of the women interviewed, 58 (26.2%) were Bedouin of the Negev. 24 (41.4%) of them took pills containing folic acid on a regular basis. This percentage is higher than that in the Jewish women in the study who took folic acid for prevention of NTD (17%; p = 0.038). Most of the women took folic acid after the first trimester. Only a minority took daily periconceptional folic acid. Multivitamins containing 0.4 mg of folic acid were more popular than folic acid tablets alone. This study emphasizes the need for continuing efforts to increase consumption of folic acid and awareness of its benefits among women of childbearing age.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    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......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...... that a TTA-induced increase in hepatic fatty acid oxidation and ketogenesis drains fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects of TTA on fat mass accumulation and peripheral insulin sensitivity....

  17. Economic burden of neural tube defects and impact of prevention with folic acid: a literature review.

    Science.gov (United States)

    Yi, Yunni; Lindemann, Marion; Colligs, Antje; Snowball, Claire

    2011-11-01

    Neural tube defects (NTDs) are the second most common group of serious birth defects. Although folic acid has been shown to reduce effectively the risk of NTDs and measures have been taken to increase the awareness, knowledge, and consumption of folic acid, the full potential of folic acid to reduce the risk of NTDs has not been realized in most countries. To understand the economic burden of NTDs and the economic impact of preventing NTDs with folic acid, a systematic review was performed on relevant studies. A total of 14 cost of illness studies and 10 economic evaluations on prevention of NTDs with folic acid were identified. Consistent findings were reported across all of the cost of illness studies. The lifetime direct medical cost for patients with NTDs is significant, with the majority of cost being for inpatient care, for treatment at initial diagnosis in childhood, and for comorbidities in adult life. The lifetime indirect cost for patients with spina bifida is even greater due to increased morbidity and premature mortality. Caregiver time costs are also significant. The results from the economic evaluations demonstrate that folic acid fortification in food and preconception folic acid consumption are cost-effective ways to reduce the incidence and prevalence of NTDs. This review highlights the significant cost burden that NTDs pose to healthcare systems, various healthcare payers, and society and concludes that the benefits of prevention of NTDs with folic acid far outweigh the cost. Further intervention with folic acid is justified in countries where the full potential of folic acid to reduce the risk of NTDs has not been realized.

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

    LENUS (Irish Health Repository)

    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.

  19. Improvement of human dendritic cell culture for immunotoxicological investigations.

    Science.gov (United States)

    Hymery, N; Sibiril, Y; Parent-Massin, D

    2006-07-01

    A toxic injury such as a decrease in the number of immature dendritic cells caused by a cytotoxic effect or a disturbance in their maturation process can be responsible for immunodepression. There is a need to improve in vitro assays on human dendritic cells used to detect and evaluate adverse effects of xenobiotics. Two aspects were explored in this work: cytotoxic effects of xenobiotics on immature dendritic cells, and the interference of xenobiotics with dendritic cell maturation. Dendritic cells of two different origins were tested. Dendritic cells obtained either from umbilical cord blood CD34(+) cells or, for the first time, from umbilical cord blood monocytes. The cytotoxicity assay on immature dendritic cells has been improved. For the study of the potential adverse effects of xenobiotics on the maturation process of dendritic cells, several parameters were selected such as expression of markers (CD86, CD83, HLA-DR), secretion of interleukins 10 and 12, and proliferation of autologous lymphocytes. The relevance and the efficiency of the protocol applied were tested using two mycotoxins, T-2 toxin and deoxynivalence, DON, which are known to be immunosuppressive, and one phycotoxin, domoic acid, which is known not to have any immunotoxic effect. Assays using umbilical cord monocyte dendritic cell cultures with the protocol defined in this work, which involves a cytotoxicity study followed by evaluation of several markers of adverse effects on the dendritic cell maturation process, revealed their usefulness for investigating xenobiotic immunotoxicity toward immune primary reactions.

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

    Directory of Open Access Journals (Sweden)

    Jariya Umka Welbat

    2016-05-01

    Full Text Available 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 asiatica. Our previous study has shown that Asiatic acid improves working spatial memory and increases cell proliferation in the sub granular zone of the hippocampal dentate gyrus. In the present study we investigate the effects of Asiatic acid in preventing the memory and cellular effects of VPA. Male Spraque-Dawley rats were orally administered Asiatic acid (30 mg/kg/day for 28 days, while VPA-treated animals received injections of VPA (300 mg/kg twice a day from Day 15 to Day 28 for 14 days. Spatial memory was determined using the novel object location (NOL test and hippocampal cell proliferation and survival was quantified by immuostaining for Ki-67 and Bromodeoxyuridine (BrdU, respectively. The results showed that VPA-treated animals were unable to discriminate between objects in familiar and novel locations. Moreover, VPA significantly reduced numbers of Ki-67 and BrdU positive cells. These results indicate that VPA treatment caused impairments of spatial working memory, cell proliferation and survival in the subgranular zone (SGZ of the hippocampal dentate gyrus (DG. However, these abnormalities were restored to control levels by co-treatment with Asiatic acid. These data demonstrate that Asiatic acid could prevent the spatial memory and neurogenesis impairments caused by VPA.

  1. Preventive effects of folic acid supplementation on adverse maternal and fetal outcomes.

    Directory of Open Access Journals (Sweden)

    Min Woo Kim

    Full Text Available Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL. In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL. The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09-0.76 and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18-0.99 were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes.

  2. Preventive effects of folic acid supplementation on adverse maternal and fetal outcomes.

    Science.gov (United States)

    Kim, Min Woo; Ahn, Ki Hoon; Ryu, Ki-Jin; Hong, Soon-Cheol; Lee, Ji Sung; Nava-Ocampo, Alejandro A; Oh, Min-Jeong; Kim, Hai-Joong

    2014-01-01

    Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09-0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18-0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes.

  3. Role of folic acid supplementation in prevention of neural tube defects: physicians yet unaware!

    Science.gov (United States)

    Aggarwal, A; Kumhar, G Das; Harit, D; Faridi, M M A

    2010-09-01

    Folic acid supplementation is important in the prevention of Neural Tube Defects (NTD). The study was conducted to assess the awareness amongst physicians regarding the role of Folic Acid (FA) in the prevention of NTD. Physicians were interviewed regarding the awareness of FA dose, timing of supplementation and knowledge about its role in prevention of neural tube defects using a semistructured questionnaire. Among 202 physicians interviewed (48 pediatricians, 54 obstetricians, 100 recently qualified medical graduates) overall awareness about FA was present in 92.07%, similar in three groups (P > 0.05). Only 47.52% were aware of preconception administration, 61.38% about dose of supplementation and 11.88% about recurrence rate of NTD. Only 15 (7.4%) knew all these. Regarding the etiology of NTDs only 26.7% said both FA and genetic factors are involved. Though majority were aware that folic acid has a role in prevention of NTDs, their knowledge about timing and dose of supplementation was lacking. Hence attempts should be made to increase the awareness regarding prevention of NTD's by FA supplementation at a proper time.

  4. Nucleotide precursors prevent folic acid-resistant neural tube defects in the mouse.

    Science.gov (United States)

    Leung, Kit-Yi; De Castro, Sandra C P; Savery, Dawn; Copp, Andrew J; Greene, Nicholas D E

    2013-09-01

    Closure of the neural tube during embryogenesis is a crucial step in development of the central nervous system. Failure of this process results in neural tube defects, including spina bifida and anencephaly, which are among the most common birth defects worldwide. Maternal use of folic acid supplements reduces risk of neural tube defects but a proportion of cases are not preventable. Folic acid is thought to act through folate one-carbon metabolism, which transfers one-carbon units for methylation reactions and nucleotide biosynthesis. Hence suboptimal performance of the intervening reactions could limit the efficacy of folic acid. We hypothesized that direct supplementation with nucleotides, downstream of folate metabolism, has the potential to support neural tube closure. Therefore, in a mouse model that exhibits folic acid-resistant neural tube defects, we tested the effect of specific combinations of pyrimidine and purine nucleotide precursors and observed a significant protective effect. Labelling in whole embryo culture showed that nucleotides are taken up by the neurulating embryo and incorporated into genomic DNA. Furthermore, the mitotic index was elevated in neural folds and hindgut of treated embryos, consistent with a proposed mechanism of neural tube defect prevention through stimulation of cellular proliferation. These findings may provide an impetus for future investigations of supplemental nucleotides as a means to prevent a greater proportion of human neural tube defects than can be achieved by folic acid alone.

  5. Capacity of lactic acid bacteria in immunity enhancement and cancer prevention.

    Science.gov (United States)

    Riaz Rajoka, Muhammad Shahid; Shi, Junling; Zhu, Jing; Shao, Dongyan; Huang, Qingsheng; Yang, Hui; Jin, Mingliang

    2017-01-01

    Lactic acid bacteria are associated with the human gastrointestinal tract. They are important for maintaining the balance of microflora in the human gut. An increasing number of published research reports in recent years have denoted the importance of producing interferon-gamma and IgA for treatment of disease. These agents can enhance the specific and nonspecific immune systems that are dependent on specific bacterial strains. The mechanisms of these effects were revealed in this investigation, where the cell walls of these bacteria were modulated by the cytokine pathways, while the whole bacterial cell mediated the host cell immune system and regulated the production of tumor necrosis factors and interleukins. A supplement of highly active lactic acid bacteria strains provided significant potential to enhance host's immunity, offering prevention from many diseases including some cancers. This review summarizes the current understanding of the function of lactic acid bacteria immunity enhancement and cancer prevention.

  6. Potential role of dietary n-3 fatty acids in the prevention of dementia and macular degeneration.

    Science.gov (United States)

    Johnson, Elizabeth J; Schaefer, Ernst J

    2006-06-01

    Dementia and age-related macular degeneration (AMD) are major causes of disability in the elderly. n-3 Fatty acids, particularly docosahexaenoic acid (DHA), are highly concentrated in brain and retinal tissue and may prevent or delay the progression of dementia and AMD. Low dietary intakes and plasma concentrations have been reported to be associated with dementia, cognitive decline, and AMD risk. The major dietary sources of DHA are fish and fish oils, although dietary supplements are available. At this point, it is not possible to make firm recommendations regarding n-3 fatty acids and the prevention of dementia and AMD. Our own unpublished observations from the Framingham Heart Study suggest that > or =180 mg/d of dietary DHA (approximately 2.7 fish servings/wk) is associated with an approximately 50% reduction in dementia risk. At least this amount of DHA is generally found in one commercially available 1-g fish oil capsule given daily.

  7. Omega-3 fatty acids in the prevention and control of cardiovascular disease.

    Science.gov (United States)

    Mata López, P; Ortega, R M

    2003-09-01

    Cardiovascular disease is one of the main causes of death in developed countries. Several factors are involved in its appearance and progress, among which nutrition enjoys a certain protagonism. Until recently, the dietetic criteria for preventing and controlling cardiovascular disease were mainly restrictive (at least in terms of energy and fat intake), but such advice is difficult to follow, and without careful monitoring can lead to deficiencies that might negatively affect quality of life and perhaps even life expectancy. Several investigations show that some components of the lipid fraction of the diet, such as omega-3 fatty acids, are beneficial with respect to cardiovascular disease, and these have become the centre of much attention. This paper reviews the results of some of these studies and evaluates the benefit of these fatty acids in the prevention of coronary heart disease. The sources of omega-3 fatty acids, their recommended consumption, possible mechanisms of action and potential adverse effects are discussed.

  8. Folic acid in cleft lip, alveolus and palate prevention: Awareness among dental professionals

    Directory of Open Access Journals (Sweden)

    Elavenil P

    2010-01-01

    Full Text Available Objectives : To determine the awareness amongst dental students, practitioners and maxillofacial surgeons the role of folic acid in the prevention of CLAP and its clinical use. Materials and Methods : Questionnaire based study involving a sample base of 1100, comprising of dental students, practitioners and specialist maxillofacial surgeons. Results : hundred percent of the sample population were aware of CLAP disorders, of which 9.5 % believed that CLAP could be prevented. 3.8 % of the population were able to correlate folic acid to CLAP while a negligible 0.03 % could provide the dosage. Conclusion : Educating healthcare providers and, in turn, the prospective parents on benefits folic acid would not only help in reducing the incidence of CLAP but also significantly influence the economics of the patients afflicted with CLAP disorders.

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

    Science.gov (United States)

    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.

  10. Awareness of folic acid for neural tube defect prevention among Israeli women.

    Science.gov (United States)

    Ringel, S; Lahat, E; Elizov, T; Greenberg, R; Arieli, S; Afriat, R; Berkovitch, M

    1999-07-01

    The failure of neural tube closure during early embryogenesis results in a range of neural tube defects (NTD), the most common of which is spina bifida. The role of folic acid in reducing the rate of NTD has been well-established. Three recent cases of infants with NTD inspired this investigative study into the level of awareness and knowledge of folic acid and its function in the prevention of NTD among Israeli women. Of 920 women interviewed, only 51 (5.5%) had heard of folic acid, and 27 (2.8%) were reported to have taken it. The source of information and the motivation for self-medication were also explored with regard to socioeconomic and health profile. Awareness of folic acid was significant among women aged 17-29 years (P = 0.005) and those aged 30-39 years (P = 0.009), and among semireligious and nonreligious women (P = 0.008 and 0.01, respectively). Among women who were aware of folic acid, only nonreligious women tended to take it. No correlation was found between folic acid intake and age, religiosity, nationality, number of pregnancies, and health status among women who were aware of folic acid intake. The poor level of awareness, evident in our study, demands that the medical community broadcast the benefit of folic acid. Furthermore, government health initiatives, such as the addition of folic acid to flour preparations, may effectively ensure its appropriate daily intake. These improved education and prevention programs may forcibly reduce the rate of NTD-affected pregnancies.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Phagosomal Acidification Prevents Macrophage Inflammatory Cytokine Production to Malaria, and Dendritic Cells Are the Major Source at the Early Stages of Infection: IMPLICATION FOR MALARIA PROTECTIVE IMMUNITY DEVELOPMENT.

    Science.gov (United States)

    Wu, Xianzhu; Gowda, Nagaraj M; Gowda, D Channe

    2015-09-18

    Inflammatory cytokines produced at the early stages of malaria infection contribute to shaping protective immunity and pathophysiology. To gain mechanistic insight into these processes, it is important to understand the cellular origin of cytokines because both cytokine input and cytokine-producing cells play key roles. Here, we determined cytokine responses by monocytes, macrophages, and dendritic cells (DCs) to purified Plasmodium falciparum and Plasmodium berghei ANKA, and by spleen macrophages and DCs from Plasmodium yoelii 17NXL-infected and P. berghei ANKA-infected mice. The results demonstrate that monocytes and macrophages do not produce inflammatory cytokines to malaria parasites and that DCs are the primary source early in infection, and DC subsets differentially produce cytokines. Importantly, blocking of phagosomal acidification by inhibiting vacuolar-type H(+)-ATPase enabled macrophages to elicit cytokine responses. Because cytokine responses to malaria parasites are mediated primarily through endosomal Toll-like receptors, our data indicate that the inability of macrophages to produce cytokines is due to the phagosomal acidification that disrupts endosomal ligand-receptor engagement. Macrophages efficiently produced cytokines to LPS upon simultaneously internalizing parasites and to heat-killed Escherichia coli, demonstrating that phagosomal acidification affects endosomal receptor-mediated, but not cell surface receptor-mediated, recognition of Toll-like receptor agonists. Enabling monocytes/macrophages to elicit immune responses to parasites by blocking endosomal acidification can be a novel strategy for the effective development of protective immunity to malaria. The results have important implications for enhancing the efficacy of a whole parasite-based malaria vaccine and for designing strategies for the development of protective immunity to pathogens that induce immune responses primarily through endosomal receptors.

  13. 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

    Directory of Open Access Journals (Sweden)

    Jintao Xu

    2016-07-01

    Full Text Available 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.

  14. MCS-18, a novel natural product isolated from Helleborus purpurascens, inhibits dendritic cell activation and prevents autoimmunity as shown in vivo using the EAE model.

    Science.gov (United States)

    Horstmann, Brigitte; Zinser, Elisabeth; Turza, Nadine; Kerek, Franz; Steinkasserer, Alexander

    2007-01-01

    Here we report for the first time that MCS-18, a novel natural product isolated from Helleborus purpurascens, is able to inhibit the expression of typical molecules of mature dendritic cells (DC) such as CD80, CD86, and especially of CD83 subsequently leading to a clear and dose-dependent inhibition of the DC-mediated T-cell stimulation. Furthermore, MCS-18 impeded the formation of the typical DC/T-cell clusters, which are essential to induce potent immune responses. Interestingly, MCS-18 also inhibited CCR7 expression on DC which subsequently lead to a dose-dependent block of the CCL19-mediated DC migration. MCS-18 not only inhibited the DC-mediated T-cell stimulation but also the anti-CD3/anti-CD28-mediated T-cell stimulation. Strikingly, MCS-18 also strongly reduced the paralysis associated with the experimental autoimmune encephalomyelitis (EAE), which is a murine model for human multiple sclerosis, in a prophylactic as well as in a "real" therapeutic setting. Even when the EAE was induced for a second time, the MCS-18-treated animals were still protected, suggesting that MCS-18 induces a long-lasting suppressive effect. In addition, and very important for the potential practical application in humans, MCS-18 was also active when administered orally. MCS-18 treatment almost completely reduced leukocyte infiltration in the brain and in the spinal cord. In conclusion, using in vitro as well in vivo assays we were able to show that MCS-18 exerts a strong immunosuppressive activity with remarkable potential for the therapy of diseases characterized by a pathologically over-activated immune system.

  15. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention?

    Science.gov (United States)

    Miranda, Jonatan; Arias, Noemi; Fernández-Quintela, Alfredo; del Puy Portillo, María

    2014-04-01

    Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after long-term administration. Because of this and the controversial efficacy of CLA in humans, alternative biomolecules that may be used as functional ingredients have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has been reported to be a potential anti-obesity molecule which may have additional positive effects related to obesity. According to the results reported in obesity, CLNA needs to be given at higher doses than CLA to be effective. However, because of the few studies conducted so far, it is still difficult to reach clear conclusions about the potential use of these CLNAs in obesity and its related changes (insulin resistance, dyslipidemia, or inflammation). Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  16. Prevention of neural tube defects by folic acid - awareness among women of childbearing age in Slovakia.

    Science.gov (United States)

    Horn, F; Sabova, L; Pinterova, E; Hornova, J; Trnka, J

    2014-01-01

    Folic acid deficiency plays a central role in the aetiology of many congenital anomalies including neural tube defects. Protective effect of folic acid on embryo may be acquired only if taken periconceptionally. The aim of the study was to investigate the awareness about folic acid among women of childbearing age in Bratislava, Slovakia. There were 130 respondents involved in the research (106 pregnant women, 24 female students of medical faculty). Using questionnaire we acquired following data: pregnancy details, interest in diet before and during pregnancy, recommendations regarding nutrition and supplementation pre- and post-conception, knowledge about folic and other acid in 2004 and 2009. More than half of the respondents knew the sources of folic acid. The interest in the nutrition facts of the food dropped from 91 % to 58.5 %. The number of pregnant women advised about correct nutrition and folic acid supplementation before and during pregnancy increased from 16 % to 37 %. Planning the next gravidity with folic acid supplementation became greater than 21 % (38 % in 2009). Nevertheless, only 46 % of these women believed that proper food content with folic acid may prevent congenital anomalies. In a group of students planning to take folic acid periconceptionally the number raised up to 62.5 %. The results revealed low knowledge about the effect of folic acid on developing embryo among women of childbearing age. Effective intervention programs are needed with the aim to improve periconceptional intake of folic acid in 2004 and 2009. The results in both periods show low knowledge about this essential vitamin (Tab. 1, Fig. 8, Ref. 31).

  17. Epidermal cells are the primary phagocytes in the fragmentation and clearance of degenerating dendrites in Drosophila.

    Science.gov (United States)

    Han, Chun; Song, Yuanquan; Xiao, Hui; Wang, Denan; Franc, Nathalie C; Jan, Lily Yeh; Jan, Yuh-Nung

    2014-02-05

    During developmental remodeling, neurites destined for pruning often degenerate on-site. Physical injury also induces degeneration of neurites distal to the injury site. Prompt clearance of degenerating neurites is important for maintaining tissue homeostasis and preventing inflammatory responses. Here we show that in both dendrite pruning and dendrite injury of Drosophila sensory neurons, epidermal cells rather than hemocytes are the primary phagocytes in clearing degenerating dendrites. Epidermal cells act via Draper-mediated recognition to facilitate dendrite degeneration and to engulf and degrade degenerating dendrites. Using multiple dendritic membrane markers to trace phagocytosis, we show that two members of the CD36 family, croquemort (crq) and debris buster (dsb), act at distinct stages of phagosome maturation for dendrite clearance. Our finding reveals the physiological importance of coordination between neurons and their surrounding epidermis, for both dendrite fragmentation and clearance.

  18. Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications

    Science.gov (United States)

    Adisakwattana, Sirichai

    2017-01-01

    With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients. PMID:28230764

  19. Prevention of Ophthalmia Neonatorum Caused by Neisseria gonorrhoeae Using a Fatty Acid-Based Formulation

    Directory of Open Access Journals (Sweden)

    Colin P. Churchward

    2017-07-01

    Full Text Available Ophthalmia neonatorum, also called neonatal conjunctivitis, acquired during delivery can occur in the first 28 days of life. Commonly caused by the bacterial pathogen Neisseria gonorrhoeae, infection can lead to corneal scarring, perforation of the eye, and blindness. One approach that can be taken to prevent the disease is the use of an ophthalmic prophylaxis, which kills the bacteria on the surface of the eye shortly after birth. Current prophylaxes are based on antibiotic ointments. However, N. gonorrhoeae is resistant to many antibiotics and alternative treatments must be developed before the condition becomes untreatable. This study focused on developing a fatty acid-based prophylaxis. For this, 37 fatty acids or fatty acid derivatives were screened in vitro for fast antigonococcal activity. Seven candidates were identified as bactericidal at 1 mM. These seven were subjected to irritation testing using three separate methods: the bovine corneal opacity and permeability (BCOP test; the hen’s egg test—chorioallantoic membrane (HET-CAM; and the red blood cell (RBC lysis assay. The candidates were also tested in artificial tear fluid to determine whether they were effective in this environment. Four of the candidates remained effective. Among these, two lead candidates, monocaprin and myristoleic acid, displayed the best potential as active compounds in the development of a fatty acid-based prophylaxis for prevention of ophthalmia neonatorum.

  20. Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.

    Science.gov (United States)

    Melli, Giorgia; Taiana, Michela; Camozzi, Francesca; Triolo, Daniela; Podini, Paola; Quattrini, Angelo; Taroni, Franco; Lauria, Giuseppe

    2008-12-01

    The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  3. Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders

    OpenAIRE

    Su, Kuan-Pin; Matsuoka, Yutaka; Pae, Chi-Un

    2015-01-01

    Psychiatric disorders in general, and major depression and anxiety disorders in particular, account for a large burden of disability, morbidity and premature mortality worldwide. Omega-3 polyunsaturated fatty acids (PUFAs) have a range of neurobiological activities in modulation of neurotransmitters, anti-inflammation, anti-oxidation and neuroplasticity, which could contribute to psychotropic effects. Here we reviewed recent research on the benefits of omega-3 PUFA supplements in prevention a...

  4. Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss

    OpenAIRE

    Ramadoss, Jayanth; Lunde, Emilie R.; Ouyang, Nengtai; Chen, Wei-Jung A.; Cudd, Timothy A.

    2008-01-01

    Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury...

  5. Prevention

    Science.gov (United States)

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  6. Optimization principles of dendritic structure

    Directory of Open Access Journals (Sweden)

    Borst Alexander

    2007-06-01

    Full Text Available Abstract Background Dendrites are the most conspicuous feature of neurons. However, the principles determining their structure are poorly understood. By employing cable theory and, for the first time, graph theory, we describe dendritic anatomy solely on the basis of optimizing synaptic efficacy with minimal resources. Results We show that dendritic branching topology can be well described by minimizing the path length from the neuron's dendritic root to each of its synaptic inputs while constraining the total length of wiring. Tapering of diameter toward the dendrite tip – a feature of many neurons – optimizes charge transfer from all dendritic synapses to the dendritic root while housekeeping the amount of dendrite volume. As an example, we show how dendrites of fly neurons can be closely reconstructed based on these two principles alone.

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

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    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.

  8. Puerto Rican primary physicians' knowledge about folic acid supplementation for the prevention of neural tube defects.

    Science.gov (United States)

    Miranda, Ana; Dávila Torres, René R; Gorrín Peralta, José J; Montes de Longo, Idalina

    2003-12-01

    We conducted a study of a group of primary physicians in Puerto Rico to evaluate their knowledge about folic acid supplementation to prevent neural tube defects. The study design was transverse-correlational. A total of 66 primary physicians in two hospitals (public and private) participated in the study. The sample was nonrandom and opportunistic, and only those physicians present in the hospitals at the moment of distribution of the questionnaires participated. A self-administered and anonymous questionnaire was used. Descriptive statistics and cross-tabular analysis were used to describe the results of this study. Inferential statistics were also used, including Chi square and t-tests to establish the associations/differences between physician knowledge and the independent variables. Of the participants, 87.9% demonstrated an inadequate knowledge about folic acid supplementation for the prevention of neural tube defects as part of preconception care and only 12.1% demonstrated adequate knowledge. Older physicians had greater knowledge about folic acid. Also, women demonstrated greater knowledge about folic acid than did men. Most of the physicians who always recommend supplementation to their patients demonstrated a greater knowledge about folic acid, and all participants with adequate knowledge came from the public hospital. Despite a concerted effort by the Health Department of Puerto Rico to provide education in the importance of folic acid supplementation to reduce the incidence of neural tube defects, primary physicians in two Puerto Rican hospitals generally have not availed themselves of this training and showed a lack of knowledge on this important clinical issue. Copyright 2003 Wiley-Liss, Inc.

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

    Science.gov (United States)

    Ren, Ai-Guo

    2015-08-08

    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.

  10. [Folic acid and prevention of neural tube closure defects: the question is not solved yet].

    Science.gov (United States)

    Vidailhet, M; Bocquet, A; Bresson, J-L; Briend, A; Chouraqui, J-P; Dupont, C; Darmaun, D; Frelut, M-L; Ghisolfi, J; Girardet, J-P; Goulet, O; Putet, G; Rieu, D; Rigo, J; Turck, D

    2008-07-01

    Between 1981 and 1996, several interventional studies proved the efficacy of periconceptional folic acid supplementation in the prevention of neural tube closure defects (NTCD), first in women at risk (with a previous case of NTCD) and also in women of the general population in age to become pregnant. The poor observance of this supplementation led several countries (USA, Canada, Chile...) to decide mandatory folic acid fortification of cereals, which permitted a 30% (USA) to 46% (Canada) reduction in the incidence of NTCD. Moreover, this benefit was accompanied by a diminished incidence of several other malformations and of stroke and coronary accidents in elderly people. However, several papers drew attention to an increased risk of colorectal and breast cancer in relation with high blood folate levels and the use of folic acid supplements. A controlled interventional study showed a higher rate of recurrence of colic adenomas and a higher percentage of advanced adenomas in subjects receiving 1mg/day of folic acid. A recent study demonstrated an abrupt reversal of the downward trend in colorectal cancer 1 year after the beginning of cereal folic acid fortification in the USA and Canada. Two studies also reported impaired cognitive functions in elder persons with defective vitamin B(12) status. Taken in aggregate, these studies question the wisdom of a nationwide, mandatory, folic acid fortification of cereals. As of today, despite their limited preventive efficacy, a safe approach is to keep our current French recommendations and to increase the awareness of all caregivers, so as to improve the observance of these recommendations.

  11. Amphiphilic dendritic peptides: Synthesis and behavior as an organogelator and liquid crystal

    Directory of Open Access Journals (Sweden)

    Xinwu Ba

    2011-02-01

    Full Text Available New amphiphilic dendritic peptides on dendritic polyaspartic acid were designed and synthesized. The organogel and liquid crystal properties of these amphiphilic dendritic peptides were fully studied by field-emission SEM, temperature dependent FT-IR, differential scanning calorimetry, polarization optical microscopy and X-ray diffraction experiments. Amphiphilic dendritic peptides G3 show good organogel properties with a minimum gelation concentration as low as 1 wt %. Furthermore, amphiphilic dendritic peptides G3 can form a hexagonal columnar liquid crystal assembly over a wide temperature range.

  12. D-Alanylation of Teichoic Acids and Loss of Poly-N-Acetyl Glucosamine in Staphylococcus aureus during Exponential Growth Phase Enhance IL-12 Production in Murine Dendritic Cells

    DEFF Research Database (Denmark)

    Lund, Lisbeth Drozd; Ingmer, Hanne; Frokiaer, Hanne

    2016-01-01

    Staphylococcus aureus is a major human pathogen that has evolved very efficient immune evading strategies leading to persistent colonization. During different stages of growth, S. aureus express various surface molecules, which may affect the immune stimulating properties, but very little is known...... about their role in immune stimulation and evasion. Depending on the growth phase, S. aureus may affect antigen presenting cells differently. Here, the impact of growth phases and the surface molecules lipoteichoic acid, peptidoglycan and poly-N-acetyl glucosamine on the induction of IL-12 imperative...... for an efficient clearance of S. aureus was studied in dendritic cells (DCs). Exponential phase (EP) S. aureus was superior to stationary phase (SP) bacteria in induction of IL-12, which required actin-mediated endocytosis and endosomal acidification. Moreover, addition of staphylococcal cell wall derived...

  13. Lipoic acid prevents fructose-induced changes in liver carbohydrate metabolism: role of oxidative stress.

    Science.gov (United States)

    Castro, María C; Francini, Flavio; Gagliardino, Juan J; Massa, María L

    2014-03-01

    Fructose administration rapidly induces oxidative stress that triggers compensatory hepatic metabolic changes. We evaluated the effect of an antioxidant, R/S-α-lipoic acid on fructose-induced oxidative stress and carbohydrate metabolism changes. Wistar rats were fed a standard commercial diet, the same diet plus 10% fructose in drinking water, or injected with R/S-α-lipoic acid (35mg/kg, i.p.) (control+L and fructose+L). Three weeks thereafter, blood samples were drawn to measure glucose, triglycerides, insulin, and the homeostasis model assessment-insulin resistance (HOMA-IR) and Matsuda indices. In the liver, we measured gene expression, protein content and activity of several enzymes, and metabolite concentration. Comparable body weight changes and calorie intake were recorded in all groups after the treatments. Fructose fed rats had hyperinsulinemia, hypertriglyceridemia, higher HOMA-IR and lower Matsuda indices compared to control animals. Fructose fed rats showed increased fructokinase gene expression, protein content and activity, glucokinase and glucose-6-phosphatase gene expression and activity, glycogen storage, glucose-6-phosphate dehydrogenase mRNA and enzyme activity, NAD(P)H oxidase subunits (gp91(phox) and p22(phox)) gene expression and protein concentration and phosphofructokinase-2 protein content than control rats. All these changes were prevented by R/S-α-lipoic acid co-administration. Fructose induces hepatic metabolic changes that presumably begin with increased fructose phosphorylation by fructokinase, followed by adaptive changes that attempt to switch the substrate flow from mitochondrial metabolism to energy storage. These changes can be effectively prevented by R/S-α-lipoic acid co-administration. Control of oxidative stress could be a useful strategy to prevent the transition from impaired glucose tolerance to type 2 diabetes. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Glutamic acid not beneficial for the prevention of vincristine neurotoxicity in children with cancer.

    Science.gov (United States)

    Bradfield, Scott M; Sandler, Eric; Geller, Thomas; Tamura, Roy N; Krischer, Jeffrey P

    2015-06-01

    Vincristine causes known side effects of peripheral sensory, motor, autonomic and cranial neuropathies. No preventive interventions are known. We performed a randomized, placebo-controlled, double-blind trial of oral glutamic acid as a preventive agent in pediatric patients with cancer who would be receiving vincristine therapy for at least 9 consecutive weeks (Stratum 1 = Wilms tumor and rhabdomyosarcoma) or 4 consecutive weeks in conjunction with steroids (Stratum 2 = Acute lymphoblastic leukemia and non-Hodgkin lymphoma). At designated time points, a scored neurologic exam using the Modified Balis Pediatric Scale of Peripheral Neuropathies was performed to document neurologic toxicity. Between 2007 and 2012, 250 patients were enrolled (Stratum 1 = 50, Stratum 2 = 200). The glutamic acid treated group did not have a significantly lower percentage of neurotoxicity compared to placebo treated group either overall or within stratum or age subgroups. The only subgroup which was suggestive of treatment effect was for age. Patients 13 years or older showed a larger benefit in favor of glutamic acid (P = 0.055) compared to patients less than 13 years (P = 1.00). Constipation was the most frequently reported (14%) Grade II or higher neurotoxicity. Vincristine-associated neurotoxicity in pediatric oncology remains a frequent complication of chemotherapy for multiple diagnoses with an approximate 30% of patients affected. Glutamic acid is not effective for prevention in pre-adolescents. There is a suggestion of benefit in patients 13 years or older, but the study was not designed to provide adequate power to test the treatment effect within this age group alone. © 2014 Wiley Periodicals, Inc.

  15. RAB-10 Regulates Dendritic Branching by Balancing Dendritic Transport.

    Directory of Open Access Journals (Sweden)

    Caitlin A Taylor

    2015-12-01

    Full Text Available The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors throughout the dendrite is not well understood. Here we identify the small GTPase RAB-10 and the exocyst complex as critical regulators of dendrite morphogenesis and patterning in the C. elegans sensory neuron PVD. In rab-10 mutants, PVD dendritic branches are reduced in the posterior region of the cell but are excessive in the distal anterior region of the cell. We also demonstrate that the dendritic branch distribution within PVD depends on the balance between the molecular motors kinesin-1/UNC-116 and dynein, and we propose that RAB-10 regulates dendrite morphology by balancing the activity of these motors to appropriately distribute branching factors, including the transmembrane receptor DMA-1.

  16. 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

    DEFF Research Database (Denmark)

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

    2006-01-01

    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...

  17. Effect of loess for preventing contamination of acid mine drainage from coal waste

    Institute of Scientific and Technical Information of China (English)

    MA Bao-guo; WANG Hui-yong; GAO Ran; LI Shu-li

    2012-01-01

    Acid mine drainage (AMD) that releases highly acidic,sulfate and metals-rich drainage is a serious environmental problem in coal mining areas in China.In order to study the effect of using loess for preventing AMD and controlling heavy metals contamination from coal waste,the column leaching tests were conducted.The results come from experiment data analyses show that the loess can effectively immobilize cadmium,copper,iron,lead and zinc in AMD from coal waste,increase pH value,and decrease Eh,EC,and SO42-concentrations of AMD from coal waste.The oxidation of sulfide in coal waste is prevented by addition of the loess,which favors the generation and adsorption of the alkalinity,the decrease of the population of Thiobacillus ferrooxidans,the heavy metals immobilization by precipitation of sulfide and carbonate through biological sulfate reduction inside the column,and the halt of the oxidation process of sulfide through iron coating on the surface of sulfide in coal waste.The loess can effectively prevent AMD and heavy metals contamination from coal waste in in-situ treatment systems.

  18. Brain-derived neurotrophic factor mediates activity-dependent dendritic growth in nonpyramidal neocortical interneurons in developing organotypic cultures.

    Science.gov (United States)

    Jin, Xiaoming; Hu, Hang; Mathers, Peter H; Agmon, Ariel

    2003-07-02

    Brain-derived neurotrophic factor (BDNF) promotes postnatal maturation of GABAergic inhibition in the cerebral and cerebellar cortices, and its expression and release are enhanced by neuronal activity, suggesting that it acts in a feedback manner to maintain a balance between excitation and inhibition during development. BDNF promotes differentiation of cerebellar, hippocampal, and neostriatal inhibitory neurons, but its effects on the dendritic development of neocortical inhibitory interneurons remain unknown. Here, we show that BDNF mediates depolarization-induced dendritic growth and branching in neocortical interneurons. To visualize inhibitory interneurons, we biolistically transfected organotypic cortical slice cultures from neonatal mice with green fluorescent protein (GFP) driven by the glutamic acid decarboxylase (GAD)67 promoter. Nearly all GAD67-GFP-expressing neurons were nonpyramidal, many contained GABA, and some expressed markers of neurochemically defined GABAergic subtypes, indicating that GAD67-GFP-expressing neurons were GABAergic. We traced dendritic trees from confocal images of the same GAD67-GFP-expressing neurons before and after a 5 d growth period, and quantified the change in total dendritic length (TDL) and total dendritic branch points (TDBPs) for each neuron. GAD67-GFP-expressing neurons growing in control medium exhibited a 20% increase in TDL, but in 200 ng/ml BDNF or 10 mm KCl, this increase nearly doubled and was accompanied by a significant increase in TDBPs. Blocking action potentials with TTX did not prevent the BDNF-induced growth, but antibodies against BDNF blocked the growth-promoting effect of KCl. We conclude that BDNF, released by neocortical pyramidal neurons in response to depolarization, enhances dendritic growth and branching in nearby inhibitory interneurons.

  19. n-3 Polyunsaturated Fatty Acids: Promising Nutrients for Preventing Cardiovascular Disease.

    Science.gov (United States)

    Yagi, Shusuke; Fukuda, Daiju; Aihara, Ken-Ichi; Akaike, Masashi; Shimabukuro, Michio; Sata, Masataka

    2017-08-24

    The adoption of the Western-style diet, with decreased fish intake and lack of exercise, has increased the prevalence of cardiovascular disease (CVD) in Japan. Statin treatment has been established to reduce the risk of cardiovascular events; however, 60%-70% of these events occur despite its use. Thus, the residual risk for CVD should be identified and resolved to reduce further cardiovascular events. The serum levels of n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid and docosahexaenoic acid, are reportedly associated with an increased incidence of cardiovascular events and mortality, whereas the addition of n-3 PUFA treatment to the statin treatment decreases cardiovascular events. Similar to statins, n-3 PUFAs have pleiotropic effects in addition to lipid-modifying effects. Pre-clinical and clinical studies have shown that n-3 PUFAs prevent cardiovascular events by ameliorating endothelial function and attenuating lipid accumulation, vascular inflammation, and macrophage recruitment, thereby causing coronary plaque development and rupture. Taken together, n-3 PUFAs are comprehensively able to attenuate the atherogenic response. Therefore, n-3 PUFA intake is recommended to prevent cardiovascular events, particularly in patients with multiple cardiovascular risk factors.

  20. alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells.

    Science.gov (United States)

    Sabharwal, Anup K; May, James M

    2008-02-01

    Both alpha-lipoic acid (LA) and ascorbic acid (vitamin C) have been shown to improve endothelial dysfunction, a precursor of atherosclerosis. Since oxidant stress can cause endothelial dysfunction, we tested the interaction and efficacy of these antioxidants in preventing oxidant damage to lipids due to both intra- and extracellular oxidant stresses in EA.hy926 endothelial cells. LA spared intracellular ascorbate in culture and in response to an intracellular oxidant stress induced by the redox cycling agent menadione. Extracellular oxidant stress generated by incubating cells for 2 h in with 0.2 mg/ml LDL and 5 muM Cu2+ caused a time-dependent increase of the lipid peroxidation product malondialdehyde in both cells and LDL, preceded by rapid disappearance of; alpha-tocopherol in LDL. alpha-Lipoic acid at concentrations of 40-80 microM blunted these effects. Similarly, intracellular ascorbate concentrations of 1-2 mM also prevented Cu2+-induced lipid peroxidation in LDL and cells. Cu2+-dependent oxidation of LDL in the presence of ascorbate-loaded cells decreased intracellular ascorbate by 20%, but this decrease was not reversed by LA. Both LA and ascorbate protect endothelial cells and LDL from either intra- or extracellular oxidant stress, but that LA does not spare ascorbate in oxidatively stressed cells.

  1. Ketogenic essential amino acids modulate lipid synthetic pathways and prevent hepatic steatosis in mice.

    Directory of Open Access Journals (Sweden)

    Yasushi Noguchi

    Full Text Available BACKGROUND: Although dietary ketogenic essential amino acid (KAA content modifies accumulation of hepatic lipids, the molecular interactions between KAAs and lipid metabolism are yet to be fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS: We designed a diet with a high ratio (E/N of essential amino acids (EAAs to non-EAAs by partially replacing dietary protein with 5 major free KAAs (Leu, Ile, Val, Lys and Thr without altering carbohydrate and fat content. This high-KAA diet was assessed for its preventive effects on diet-induced hepatic steatosis and whole-animal insulin resistance. C57B6 mice were fed with a high-fat diet, and hyperinsulinemic ob/ob mice were fed with a high-fat or high-sucrose diet. The high-KAA diet improved hepatic steatosis with decreased de novo lipogenesis (DNL fluxes as well as reduced expressions of lipogenic genes. In C57B6 mice, the high-KAA diet lowered postprandial insulin secretion and improved glucose tolerance, in association with restored expression of muscle insulin signaling proteins repressed by the high-fat diet. Lipotoxic metabolites and their synthetic fluxes were also evaluated with reference to insulin resistance. The high-KAA diet lowered muscle and liver ceramides, both by reducing dietary lipid incorporation into muscular ceramides and preventing incorporation of DNL-derived fatty acids into hepatic ceramides. CONCLUSION: Our results indicate that dietary KAA intake improves hepatic steatosis and insulin resistance by modulating lipid synthetic pathways.

  2. Unsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages[S

    Science.gov (United States)

    L'homme, Laurent; Esser, Nathalie; Riva, Laura; Scheen, André; Paquot, Nicolas; Piette, Jacques; Legrand-Poels, Sylvie

    2013-01-01

    The NLRP3 inflammasome is involved in many obesity-associated diseases, such as type 2 diabetes, atherosclerosis, and gouty arthritis, through its ability to induce interleukin (IL)-1β release. The molecular link between obesity and inflammasome activation is still unclear, but free fatty acids have been proposed as one triggering event. Here we reported opposite effects of saturated fatty acids (SFAs) compared with unsaturated fatty acids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway. Unlike SFAs, the UFAs oleate and linoleate did not lead to IL-1β secretion. In addition, they totally prevented the IL-1β release induced by SFAs and, with less efficiency, by a broad range of NLRP3 inducers, including nigericin, alum, and monosodium urate. UFAs did not affect the transcriptional effect of SFAs, suggesting a specific effect on the NLRP3 activation. These results provide a new anti-inflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and, therefore, IL-1β processing. By this way, UFAs might play a protective role in NLRP3-associated diseases. PMID:24006511

  3. Active properties of neuronal dendrites.

    Science.gov (United States)

    Johnston, D; Magee, J C; Colbert, C M; Cristie, B R

    1996-01-01

    Dendrites of neurons in the central nervous system are the principal sites for excitatory synaptic input. Although little is known about their function, two disparate perspectives have arisen to describe the activity patterns inherent to these diverse tree-like structures. Dendrites are thus considered either passive or active in their role in integrating synaptic inputs. This review follows the history of dendritic research from before the turn of the century to the present, with a primary focus on the hippocampus. A number of recent techniques, including high-speed fluorescence imaging and dendritic patch clamping, have provided new information and perspectives about the active properties of dendrites. The results support previous notions about the dendritic propagation of action potentials and also indicate which types of voltage-gated sodium and calcium channels are expressed and functionally active in dendrites. Possible roles for the active properties of dendrites in synaptic plasticity and integration are also discussed.

  4. Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders.

    Science.gov (United States)

    Su, Kuan-Pin; Matsuoka, Yutaka; Pae, Chi-Un

    2015-08-31

    Psychiatric disorders in general, and major depression and anxiety disorders in particular, account for a large burden of disability, morbidity and premature mortality worldwide. Omega-3 polyunsaturated fatty acids (PUFAs) have a range of neurobiological activities in modulation of neurotransmitters, anti-inflammation, anti-oxidation and neuroplasticity, which could contribute to psychotropic effects. Here we reviewed recent research on the benefits of omega-3 PUFA supplements in prevention against major depression, bipolar disorders, interferon-α-induced depression patients with chronic hepatitis C viral infection, and posttraumatic stress disorder. The biological mechanisms underlying omega-3 PUFAs'psychotropic effects are proposed and reviewed. Nutrition is a modifiable environmental factor that might be important in prevention medicine, which have been applied for many years in the secondary prevention of heart disease with omega-3 PUFAs. This review extends the notion that nutrition in psychiatry is a modifiable environmental factor and calls for more researches on prospective clinical studies to justify the preventive application of omega-3 PUFAs in daily practice.

  5. Prevention

    DEFF Research Database (Denmark)

    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....

  6. Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects

    OpenAIRE

    Moreno-Vinasco, Liliana; Verbout, Norah G.; Fryer, Allison D.; Jacoby, David B.

    2009-01-01

    Inhibitory M2 muscarinic receptors on airway parasympathetic nerves normally limit acetylcholine release. Viral infections decrease M2 receptor function, increasing vagally mediated bronchoconstriction. Since retinoic acid deficiency causes M2 receptor dysfunction, we tested whether retinoic acid would prevent virus-induced airway hyperreactivity and prevent M2 receptor dysfunction. Guinea pigs infected with parainfluenza virus were hyperreactive to electrical stimulation of the vagus nerves,...

  7. Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

    Science.gov (United States)

    Žiberna, Lovro; Šamec, Dunja; Mocan, Andrei; Nabavi, Seyed Fazel; Bishayee, Anupam; Farooqi, Ammad Ahmad; Sureda, Antoni; Nabavi, Seyed Mohammad

    2017-01-01

    Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5′ adenosine monophosphate-activated protein kinase, extracellular signal–regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical. PMID:28300756

  8. Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

    Directory of Open Access Journals (Sweden)

    Lovro Žiberna

    2017-03-01

    Full Text Available Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5′ adenosine monophosphate-activated protein kinase, extracellular signal–regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical.

  9. Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer

    Science.gov (United States)

    Vasudevan, Anita; Yu, Yingjie; Banerjee, Sanjeev; Woods, James; Farhana, Lulu; Rajendra, Sindhu G.; Patel, Aamil; Dyson, Gregory; Levi, Edi; Maddipati, Krishna Rao; Majumdar, Adhip P.N.; Nangia-Makker, Pratima

    2014-01-01

    Increasing evidence supports the contention that many malignancies, including sporadic colorectal cancer (CRC), are driven by the self-renewing, chemotherapy-resistant cancer stem/stem-like cells (CSCs/CSLCs) underscoring the need for improved preventive and therapeutic strategies targeting CSCs/CSLCs. Omega-3 polyunsaturated fatty acids (ω-3 PUFA), have been reported to inhibit the growth of primary tumors, but their potential as a preventive agent for recurring cancers is un-explored. The primary objectives of this investigation are to examine whether eicosapentaenoic acid (EPA; one of the ω-3 PUFA) synergizes with FuOx (5-FU+Oxaliplatin), the backbone of colon cancer chemotherapy, and (b) whether EPA by itself or in combination with conventional chemotherapy prevents the recurrence of colon cancer via eliminating/suppressing CSCs/CSLCs. FuOx-resistant (chemo-resistant; CR) colon cancer cells, highly enriched in CSCs, were utilized for this study. While EPA alone was effective, combination of EPA and FuOx was more potent in (a) inhibiting cell growth, colonosphere formation and sphere-forming frequency, (b) increasing sphere disintegration, (c) suppressing the growth of SCID mice xenografts of CR colon cancer cells, and (d) decreasing pro-inflammatory metabolites in mice. Additionally, EPA + FuOx caused a reduction in CSC/CSLC population. The growth reduction by this regimen is the result of increased apoptosis as evidenced by PARP cleavage. Furthermore, increased pPTEN, decreased pAkt, normalization of β-catenin expression, localization and transcriptional activity by EPA suggests a role for PTEN/Akt axis and Wnt signaling in regulating this process. Our data suggest that EPA by itself or in combination with FuOx could be an effective preventive strategy for recurring CRC. PMID:25193342

  10. Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer.

    Science.gov (United States)

    Vasudevan, Anita; Yu, Yingjie; Banerjee, Sanjeev; Woods, James; Farhana, Lulu; Rajendra, Sindhu G; Patel, Aamil; Dyson, Gregory; Levi, Edi; Maddipati, Krishna Rao; Majumdar, Adhip P N; Nangia-Makker, Pratima

    2014-11-01

    Increasing evidence supports the contention that many malignancies, including sporadic colorectal cancer, are driven by the self-renewing, chemotherapy-resistant cancer stem/stem-like cells (CSC/CSLC), underscoring the need for improved preventive and therapeutic strategies targeting CSCs/CSLCs. Omega-3 polyunsaturated fatty acids (ω-3 PUFA), have been reported to inhibit the growth of primary tumors, but their potential as a preventive agent for recurring cancers is unexplored. The primary objectives of this investigation are (i) to examine whether eicosapentaenoic acid (EPA; one of the ω-3 PUFA) synergizes with FuOx (5-FU+Oxaliplatin), the backbone of colon cancer chemotherapy, and (ii) whether EPA by itself or in combination with conventional chemotherapy prevents the recurrence of colon cancer via eliminating/suppressing CSCs/CSLCs. FuOx-resistant (chemoresistant; CR) colon cancer cells, highly enriched in CSCs, were used for this study. Although EPA alone was effective, combination of EPA and FuOx was more potent in (i) inhibiting cell growth, colonosphere formation, and sphere-forming frequency, (ii) increasing sphere disintegration, (iii) suppressing the growth of SCID mice xenografts of CR colon cancer cells, and (iv) decreasing proinflammatory metabolites in mice. In addition, EPA + FuOx caused a reduction in CSC/CSLC population. The growth reduction by this regimen is the result of increased apoptosis as evidenced by PARP cleavage. Furthermore, increased pPTEN, decreased pAkt, normalization of β-catenin expression, localization, and transcriptional activity by EPA suggests a role for the PTEN-Akt axis and Wnt signaling in regulating this process. Our data suggest that EPA by itself or in combination with FuOx could be an effective preventive strategy for recurring colorectal cancer.

  11. α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria.

    Science.gov (United States)

    Zee, Tiffany; Bose, Neelanjan; Zee, Jarcy; Beck, Jennifer N; Yang, See; Parihar, Jaspreet; Yang, Min; Damodar, Sruthi; Hall, David; O'Leary, Monique N; Ramanathan, Arvind; Gerona, Roy R; Killilea, David W; Chi, Thomas; Tischfield, Jay; Sahota, Amrik; Kahn, Arnold; Stoller, Marshall L; Kapahi, Pankaj

    2017-03-01

    Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutritional supplement α-lipoic acid inhibits cystine stone formation in the Slc3a1(-/-) mouse model of cystinuria by increasing the solubility of urinary cystine. These findings identify a novel therapeutic strategy for the clinical treatment of cystinuria.

  12. Isothermal Dendritic Growth Experiment Video

    Science.gov (United States)

    1997-01-01

    This video, captured during the Isothermal Dendritic Growth Experiment (IDGE) flown on STS-87 as a part of the fourth United States Microgravity payload, shows the growth of a dendrite, and the surface solidification that occurred on the front and back windows of the growth chamber. Dendrites are tiny, tree like structures that form as metals solidify.

  13. Efficacy of Organic Acids in Hand Cleansers for Prevention of Rhinovirus Infections

    Science.gov (United States)

    Turner, Ronald B.; Biedermann, Kim A.; Morgan, Jeffery M.; Keswick, Bruce; Ertel, Keith D.; Barker, Mark F.

    2004-01-01

    Direct hand-to-hand contact is an important mechanism of transmission of rhinovirus infection. The rhinoviruses are inactivated at a low pH. A survey of organic acids in vitro revealed that these compounds have antirhinoviral activity that persists for at least 3 h after application to the skin. In additional studies of salicylic acid (SA) and pyroglutamic acid (PGA), the hands of volunteers were contaminated with rhinovirus at defined times after application of the acid, and then volunteers attempted to inoculate the nasal mucosa with one hand and quantitative viral cultures were done on the other hand. In one study, 3.5% SA or 1% SA with 3.5% PGA was compared with controls 15 min after application to assess the efficacy of the inactivation of virus and prevention of infection. Virus was recovered from the hands of 28 out of 31 (90%) of the volunteers in the control group compared to 4 out of 27 (15%) and 0 out of 27 in the groups administered 3.5 and 1% SA, respectively (P < 0.05). Rhinovirus infection occurred in 10 out of 31 (32%) of the controls and 2 out of 27 (7%) of volunteers in both treatment groups (P < 0.05 compared with control). In a second study, the efficacy of 4% PGA was evaluated 15 min, 1 h, and 3 h after application. Significantly fewer volunteers had positive hand cultures at all time points compared with the control group, but the proportion that developed rhinovirus infection was not significantly reduced. These results suggest the feasibility of the prevention of rhinovirus transmission by hand treatments that are virucidal on contact and have activity that persists after application. PMID:15215114

  14. Chronic glucocorticoids increase hippocampal vulnerability to neurotoxicity under conditions that produce CA3 dendritic retraction but fail to impair spatial recognition memory.

    Science.gov (United States)

    Conrad, Cheryl D; McLaughlin, Katie J; Harman, James S; Foltz, Cainan; Wieczorek, Lindsay; Lightner, Elizabeth; Wright, Ryan L

    2007-08-01

    We previously found that chronic stress conditions producing CA3 dendritic retraction and spatial memory deficits make the hippocampus vulnerable to the neurotoxin ibotenic acid (IBO). The purpose of this study was to determine whether exposure to chronic corticosterone (CORT) under conditions that produce CA3 dendritic retraction would enhance CA3 susceptibility to IBO. Male Sprague Dawley rats were chronically treated for 21 d with CORT in drinking water (400 microg/ml), and half were given daily injections of phenytoin (40 mg/kg), an antiepileptic drug that prevents CA3 dendritic retraction. Three days after treatments stopped, IBO was infused into the CA3 region. Conditions producing CA3 dendritic retraction (CORT and vehicle) exacerbated IBO-induced CA3 damage compared with conditions in which CA3 dendritic retraction was not observed (vehicle and vehicle, vehicle and phenytoin, CORT and phenytoin). Additionally, spatial recognition memory was assessed using the Y-maze, revealing that conditions producing CA3 dendritic retraction failed to impair spatial recognition memory. Furthermore, CORT levels in response to a potentially mild stressor (injection and Y-maze exposure) stayed at basal levels and failed to differ among key groups (vehicle and vehicle, CORT and vehicle, CORT and phenytoin), supporting the interpretations that CORT levels were unlikely to have been elevated during IBO infusion and that the neuroprotective actions of phenytoin were not through CORT alterations. These data are the first to show that conditions with prolonged glucocorticoid elevations leading to structural changes in hippocampal dendritic arbors can make the hippocampus vulnerable to neurotoxic challenges. These findings have significance for many disorders with elevated glucocorticoids that include depression, schizophrenia, Alzheimer's disease, and Cushing's disease.

  15. Differential gating of dendritic spikes by compartmentalized inhibition

    Directory of Open Access Journals (Sweden)

    Katharina Anna Wilmes

    2014-03-01

    potentials into apical obliques and the basal dendrites. Proximal basal inhibition could prevent back­propagation into the basal dendrites, without preventing dendritic spikes in the apical dendrite. A quantitative investigation of these observations showed that the modulation of calcium spikes is rather insensitive to timing while inhibition of the fast back-propagating action potential required precisely timed inhibition within a window of 1ms of the initiation of the somatic action potential. Third, when inhibition was on the path between driving input and spike initiation zone, two different scenarios need to be distinguished. Either, the driving input is passively propagated to the soma, in which case modulation of the back-propagating action potential occurs under similar conditions as for somatic stimulation. Alternatively, if synaptic stimulation triggers dendritic spikes, back-propagation is impaired, abolishing the possibility of inhibitory modulation of the back-propagating action potential. Because different excitatory synaptic pathways converge onto distinct dendritic compartments, the proposed mechanism could implement a pathway-specific switch for synaptic plasticity, a potentially useful feature for learning and the formation of memories.

  16. Assessment of student pharmacists' knowledge concerning folic acid and prevention of birth defects demonstrates a need for further education.

    Science.gov (United States)

    Lynch, Sean M

    2002-03-01

    Adequate periconceptional consumption of folic acid can prevent neural tube birth defects, and all women capable of becoming pregnant are recommended to consume 400 microg/d. Most women, however, are unaware of this recommendation and do not consume adequate amounts of folic acid. It is important, therefore, that healthcare professionals, such as pharmacists, be capable of educating women regarding folic acid. The aim of this study was to assess knowledge regarding prevention of birth defects by folic acid among student (future) pharmacists in the final year of a professional degree program. Over a 3-y period (1998-2000), students (n = 98) enrolled in a PharmD program completed a survey consisting of five multiple-choice questions concerning folic acid and birth defects. Almost all students (93.9%) correctly identified folic acid as preventing birth defects. Of these students, many also knew that supplementation should begin before pregnancy (73.9%). Fewer, however, were able to correctly identify either the recommended level of intake (55.4%) or good sources of folic acid (57.6-65.2%). These results show that although student (future) pharmacists are aware of folic acid's ability to prevent birth defects, many lack the specific knowledge needed to effectively counsel women in future clinical practice.

  17. Acetylsalicylic Acid and Eflornithine in Treating Patients at High Risk for Colorectal Cancer | Division of Cancer Prevention

    Science.gov (United States)

    This phase II trial is studying how well giving acetylsalicylic acid together with eflornithine works in treating patients at high risk for colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acetylsalicylic acid and eflornithine may prevent colorectal cancer. |

  18. Transport Processes in Dendritic Crystallization

    Science.gov (United States)

    Glicksman, M. E.

    1984-01-01

    Free dentritic growth refers to the unconstrained development of crystals within a supercooled melt, which is the classical dendrite problem. The development of theoretical understanding of dendritic growth and its experimental status is sketched showing that transport theory and interfacial thermodynamics (capillarity theory) are insufficient ingredients to develop a truly predictive model of dendrite formation. The convenient, but incorrect, notion of maximum velocity was used for many years to estimate the behavior of dendritic transformations until supplanted by modern dynamic stability theory. The proper combinations of transport theory and morphological stability seem to be able to predict the salient aspects of dendritic growth, especially in the neighborhood of the tip.

  19. Docosahexaenoic Acid Supplementation Early in Pregnancy May Prevent Deep Placentation Disorders

    Directory of Open Access Journals (Sweden)

    Jorge A. Carvajal

    2014-01-01

    Full Text Available Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction. Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called “deep placentation disorders”; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

    2013-01-01

    In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-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 re-exposure 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 currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  2. Allergy-preventive effects of chlorogenic acid and iridoid derivatives from flower buds of Lonicera japonica.

    Science.gov (United States)

    Oku, Hisae; Ogawa, Yuko; Iwaoka, Emiko; Ishiguro, Kyoko

    2011-01-01

    Allergy-preventive activity of flower buds of Lonicera japonica THUNB. was found in the 35% EtOH extract (LJ) using an in vivo assay, The assay system uses monitoring of a decrease in blood flow (BF) in the tail vein of mice subjected to sensitization with hen-egg white lysozyme (HEL). Bioassay-guided fractionation of the 35% EtOH extract led to isolation of chlorogenic acid (1) and three known iridoid derivatives, loganin (2), secoxyloganin (3) and sweroside (4), all of which inhibited the BF decrease. This suggested that the flower buds of L. japonica and compounds isolated from them have allergy-preventive properties. The structure-activity relationship of iridoid derivatives, morroniside (5), geniposide (6), asperuloside (7), aucubin (8) and catalpol (9), were also tested using the same bioassay method. Compounds 2-5 and 9 having the sp(3) atom at C-8 showed an allergy-preventive effect, while compounds 6, 7 and 8 having a double bond at C-7, C-8 did not.

  3. Modification of dendritic development.

    Science.gov (United States)

    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

  4. Exploration of the preventive effect of ursolic acid on retinopathy in diabetic mice and its mechanism

    Institute of Scientific and Technical Information of China (English)

    Ai-Zhong Yu

    2016-01-01

    Objective:To study the preventive effect of ursolic acid on retinopathy in diabetic mice through adjusting insulin sensitivity, glucose transport, angiogenesis and inflammation. Methods:Male C57BL/6 mice were selected as experimental animals and randomly divided into control group (N group), model group (D group) and intervention group (D+UA group), D group and D+UA group established diabetes models through intraperitoneal injection of STZ, D+UA group received intragastric administration of ursolic acid, and then insulin sensitivity, glucose metabolism in retina as well as the expression levels of GLUTs, HIF-1α/VEGF/VEGFR2 pathway and IKKβ/IKBα/NF-κB pathway in retina tissue of three groups were detected. Results:AUC of D group was significantly lower than that of N group, and HOMA-IR, sugar content in retina tissue as well as GLUT-1, GLUT-3, HIF-1α, VEGF, VEGFR2, IKKβ, IKBα, NF-κB, TNF-α, ICAM-1, VCAM-1 and E-selectin levels were significantly higher than those of N group;AUC of D+UA group was significantly higher than that of D group, and HOMA-IR, sugar content in retina tissue as well as GLUT-1, GLUT-3, HIF-1α, VEGF, VEGFR2, IKK毬, IKBα, NF-κB, TNF-α, ICAM-1, VCAM-1 and E-selectin levels were significantly lower than those of D group. Conclusion:Ursolic acid can increase insulin sensitivity, reduce sugar content in retina tissue and inhibit angiogenesis and inflammation degree in retina tissue, and has preventive effect on retinopathy in diabetic mice.

  5. Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats

    Directory of Open Access Journals (Sweden)

    Esther Castillo-Gómez

    2016-01-01

    Full Text Available Dopamine D2 receptors (D2R in the medial prefrontal cortex (mPFC are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM, a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found.

  6. The use of folic acid for the prevention of neural tube defects and other congenital anomalies.

    Science.gov (United States)

    Wilson, R Douglas; Davies, Gregory; Désilets, Valérie; Reid, Gregory J; Summers, Anne; Wyatt, Philip; Young, David

    2003-11-01

    To provide information regarding the use of folic acid for the prevention of neural tube defects (NTDs) and other congenital anomalies, in order that physicians, midwives, nurses, and other health-care workers can assist in the education of women in the preconception phase of their health care. OPTION: Folic acid supplementation is problematic, since 50% of pregnancies are unplanned and the health status of women may not be optimal. Folic acid supplementation has been proven to decrease or minimize specific birth defects. A systematic review of the literature, including review and peer-reviewed articles, government publications, the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of March 1993, and statements from the American College of Obstetrics and Gynecology, was used to develop a new clinical practice guideline for the SOGC. Peer-review process within the committee structure. The benefit is reduced lethal and severe morbidity birth defects and the harm is minimal. The personal cost is of vitamin supplementation on a daily basis and eating a healthy diet. 1. Women in the reproductive age group should be advised about the benefits of folic acid supplementation during wellness visits (birth control renewal, Pap testing, yearly examination), especially if pregnancy is contemplated. (III-A) 2. Women should be advised to maintain a healthy nutritional diet, as recommended in Canada's Food Guide to Healthy Eating (good or excellent sources of folic acid: broccoli, spinach, peas, Brussels sprouts, corn, beans, lentils, oranges). (III-A) 3. Women who could become pregnant should be advised to take a multivitamin containing 0.4 mg to 1.0 mg of folic acid daily. (II-1A) 4. Women taking a multivitamin with folic acid supplement should be advised not to take more than 1 daily dose of vitamin supplement, as indicated on the product label. (II-2A) 5. Women in intermediate- to high-risk categories for NTDs (NTD-affected previous

  7. Stimulation of Chromobacterium lipase activity and prevention of its adsorption to palmitoyl cellulose by hydrophobic binding of fatty acids.

    Science.gov (United States)

    Horiuti, Y; Imamura, S

    1978-05-01

    Fatty acids prevented adsorption of purified Chromobacterium lipase [triacylglycerol acylhydrolase, EC 3.1.1.3] onto palmitoyl cellulose (Pal-C) and also increased the activity of the purified lipase. These effects increased with increase in the concentration and chainlength (up to 16 carbon atoms) of the fatty acids, and long-chain unsaturated fatty acids, such as oleic acid, linoleic acid and erucic acid, were most effective. When the lipase was adsorbed (immobilized) on Pal-C, its activity was elevated to 20 times that of the free lipase in detergent-free reaction mixture (olive oil-buffer system). Thus lipase was adsorbed to Pal-C through a hydrophobic site distinct from its catalytic site and the binding of fatty acids to the hydrophobic site seems to result in stimulation of the lipase activity.

  8. Metabolism Is Central to Tolerogenic Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Wen Jing Sim

    2016-01-01

    Full Text Available Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential.

  9. Stress-induced increases in brainstem amino acid levels are prevented by chronic sodium hydrosulfide treatment.

    Science.gov (United States)

    Warenycia, M W; Kombian, S B; Reiffenstein, R J

    1990-01-01

    Neurotransmitter amino acid levels were measured in select brain regions of rats and mice after chronic treatment with sublethal doses of sodium hydrosulfide (NaHS). Brainstem aspartate, glutamate, glutamine, taurine and GABA levels increased in chronically but not acutely saline-treated rats. These increases may have been due to stress from frequent handling, and were prevented by chronic NaHS treatment (7.5 mg/kg ip every 8 hr for 3 consecutive days). In contrast, aspartate, glutamate and glutamine increased in female but not in male ICR mouse brainstems after once daily treatment with 7.0 mg/kg NaHS for 5 consecutive days. These effects of NaHS may indicate chronic low level H2S neurotoxicity. Differences between chronic and acute treatments, female and male responses, and treatment paradigms may complicate interpretations of such toxicity studies.

  10. Preventing Food Allergies by Tricking Dendritic Cells

    Science.gov (United States)

    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...

  11. D-Alanylation of Teichoic Acids and Loss of Poly-N-Acetyl Glucosamine in Staphylococcus aureus during Exponential Growth Phase Enhance IL-12 Production in Murine Dendritic Cells.

    Science.gov (United States)

    Lund, Lisbeth Drozd; Ingmer, Hanne; Frøkiær, Hanne

    2016-01-01

    Staphylococcus aureus is a major human pathogen that has evolved very efficient immune evading strategies leading to persistent colonization. During different stages of growth, S. aureus express various surface molecules, which may affect the immune stimulating properties, but very little is known about their role in immune stimulation and evasion. Depending on the growth phase, S. aureus may affect antigen presenting cells differently. Here, the impact of growth phases and the surface molecules lipoteichoic acid, peptidoglycan and poly-N-acetyl glucosamine on the induction of IL-12 imperative for an efficient clearance of S. aureus was studied in dendritic cells (DCs). Exponential phase (EP) S. aureus was superior to stationary phase (SP) bacteria in induction of IL-12, which required actin-mediated endocytosis and endosomal acidification. Moreover, addition of staphylococcal cell wall derived peptidoglycan to EP S. aureus stimulated cells increased bacterial uptake but abrogated IL-12 induction, while addition of lipoteichoic acid increased IL-12 production but had no effect on the bacterial uptake. Depletion of the capability to produce poly-N-acetyl glucosamine increased the IL-12 inducing activity of EP bacteria. Furthermore, the mutant dltA unable to produce D-alanylated teichoic acids failed to induce IL-12 but like peptidoglycan and the toll-like receptor (TLR) ligands LPS and Pam3CSK4 the mutant stimulated increased macropinocytosis. In conclusion, the IL-12 response by DCs against S. aureus is highly growth phase dependent, relies on cell wall D-alanylation, endocytosis and subsequent endosomal degradation, and is abrogated by receptor induced macropinocytosis.

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

    Science.gov (United States)

    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.

  13. Salvianolic acid B, an antioxidant from Salvia miltiorrhiza, prevents 6-hydroxydopamine induced apoptosis in SH-SY5Y cells.

    Science.gov (United States)

    Tian, Lin-Lin; Wang, Xue-Jun; Sun, Yu-Ning; Li, Chun-Rong; Xing, Ya-Ling; Zhao, Hai-Bao; Duan, Ming; Zhou, Zhe; Wang, Sheng-Qi

    2008-01-01

    Oxidative stress caused by dopamine may play an important role in the pathogenesis of Parkinson's disease. Salvianolic acid B is an antioxidant derived from the Chinese herb, Salvia miltiorrhiza. In this study, we investigated the neuroprotective effect of salvianolic acid B against 6-hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells. Pretreatment of SH-SY5Y cells with salvianolic acid B significantly reduced 6-hydroxydopamine-induced generation of reactive oxygen species, and prevented 6-hydroxydopamine-induced increases in intracellular calcium. Our data demonstrated that 6-hydroxydopamine-induced apoptosis was reversed by salvianolic acid B treatment. Salvianolic acid B reduced the 6-hydroxydopamine-induced increase of caspase-3 activity, and reduced cytochrome C translocation into the cytosol from mitochondria. The 6-hydroxydopamine-induced decrease in the Bcl-x/Bax ratio was prevented by salvianolic acid B. Additionally, salvianolic acid B decreased the activation of extracellular signal-regulated kinase and induced the activation of 6-hydroxydopamine-suppressed protein kinase C. These results indicate that the protective function of salvianolic acid B is dependent upon its antioxidative potential. Our results strongly suggest that salvianolic acid B may be effective in treating neurodegenerative diseases associated with oxidative stress.

  14. Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss.

    Science.gov (United States)

    Ramadoss, Jayanth; Lunde, Emilie R; Ouyang, Nengtai; Chen, Wei-Jung A; Cudd, Timothy A

    2008-08-01

    Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury to the fetal cerebellum, one of the most sensitive targets of prenatal ethanol exposure. Pregnant ewes were intravenously infused with ethanol (258+/-10 mg/dl peak blood ethanol concentration) or saline in a "3 days/wk binge" pattern throughout the third trimester. Quantitative stereological analysis demonstrated that ethanol resulted in a 45% reduction in the total number of fetal cerebellar Purkinje cells, the cell type most sensitive to developmental ethanol exposure. Extracellular pH manipulation to create the same degree and pattern of pH fall caused by ethanol (manipulations large enough to inhibit TASK 1 channels), resulted in a 24% decrease in Purkinje cell number. We determined immunohistochemically that TASK 1 channels are expressed in Purkinje cells and that the TASK 3 isoform is expressed in granule cells of the ovine fetal cerebellum. Pharmacological blockade of both TASK 1 and TASK 3 channels simultaneous with ethanol effectively prevented any reduction in fetal cerebellar Purkinje cell number. These results demonstrate for the first time functional significance of fetal cerebellar two-pore domain pH-sensitive channels and establishes them as a potential therapeutic target for prevention of ethanol teratogenesis.

  15. Tauroursodeoxycholic acid prevents hearing loss and hair cell death in Cdh23(erl/erl) mice.

    Science.gov (United States)

    Hu, J; Xu, M; Yuan, J; Li, B; Entenman, S; Yu, H; Zheng, Q Y

    2016-03-01

    Sensorineural hearing loss has long been the subject of experimental and clinical research for many years. The recently identified novel mutation of the Cadherin23 (Cdh23) gene, Cdh23(erl/erl), was proven to be a mouse model of human autosomal recessive nonsyndromic deafness (DFNB12). Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated bile acid, has been used in experimental research and clinical applications related to liver disease, diabetes, neurodegenerative diseases, and other diseases associated with apoptosis. Because hair cell apoptosis was implied to be the cellular mechanism leading to hearing loss in Cdh23(erl/erl) mice (erl mice), this study investigated TUDCA's otoprotective effects in erl mice: preventing hearing impairment and protecting against hair cell death. Our results showed that systemic treatment with TUDCA significantly alleviated hearing loss and suppressed hair cell death in erl mice. Additionally, TUDCA inhibited apoptotic genes and caspase-3 activation in erl mouse cochleae. The data suggest that TUDCA could be a potential therapeutic agent for human DFNB12.

  16. Chlorogenic Acid Prevents Osteoporosis by Shp2/PI3K/Akt Pathway in Ovariectomized Rats

    Science.gov (United States)

    Zuo, Hui Ling; Yao, Fen Fen; Ruan, Hui Bing; Xu, Jin; Song, Wei; Zhou, Yi Cheng; Wen, Shi Yao; Dai, Jiang Hua; Zhu, Mei Lan; Luo, Jun

    2016-01-01

    Cortex Eucommiae is used worldwide in traditional medicine, various constituents of Cortex Eucommiae, such as chlorogenic acid (CGA), has been reported to exert anti-osteoporosis activity in China, but the mechanism about their contribution to the overall activity is limited. The aims of this study were to determine whether chlorogenic acid can prevent estrogen deficiency-induced osteoporosis and to analyze the mechanism of CGA bioactivity. The effect of CGA on estrogen deficiency-induced osteoporosis was performed in vivo. Sixty female Sprague-Dawley rats were divided randomly among a sham-operated group and five ovariectomy (OVX) plus treatment subgroups: saline vehicle, 17α-ethinylestradiol (E2), or CGA at 9, 27, or 45 mg/kg/d. The rats’ femoral metaphyses were evaluated by micro-computed tomography (μCT). The mechanism of CGA bioactivity was investigated in vitro. Bone mesenchymal stem cells (BMSCs) were treated with CGA, with or without phosphoinositide 3-kinase (PI3K) inhibitor LY294002. BMSCs proliferation and osteoblast differentiation were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and alkaline phosphatase, with or without Shp2 interfering RNA (RNAi). The results display that CGA at 27 and 45 mg/kg/day inhibited the decrease of bone mineral density (BMD) that induced by OVX in femur (p< 0.01), significantly promoted the levels of bone turnover markers, and prevented bone volume fraction (BV/TV), connectivity density (CoonD), trabecular number (Tb.N), trabecular thickness (Tb.Th) (all p< 0.01) to decrease and prevented the trabecular separation (Tb.Sp), structure model index (SMI)(both p< 0.01) to increase. CGA at 1 or 10 μM enhanced BMSC proliferation in a dose-dependent manner. CGA at 0.1 to 10 μM increased phosphorylated Akt (p-Akt) and cyclin D1. These effects were reversed by LY294002. CGA at 1 or 10 μM increased BMSC differentiation to osteoblasts (p< 0.01), Shp2 RNAi suppressed CGA-induced osteoblast

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

    Directory of Open Access Journals (Sweden)

    Ana Luísa Vital

    2003-01-01

    Full Text Available 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.

  18. Preventive effects of p-coumaric acid on lysosomal dysfunction and myocardial infarct size in experimentally induced myocardial infarction.

    Science.gov (United States)

    Jyoti Roy, Abhro; Stanely Mainzen Prince, P

    2013-01-15

    The present study was designed to evaluate the preventive effects of p-coumaric acid on lysosomal dysfunction and myocardial infarct size in isoproterenol induced myocardial infarcted rats. Male albino Wistar rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days after which isoproterenol (100mg/kg body weight) was injected subcutaneously into rats twice at an interval of 24h (8th and 9th day).The activity/levels of serum cardiac diagnostic markers, heart lysosomal lipid peroxidation products and the activities of lysosomal enzymes (β-glucuronidase, β-galactosidase, cathepsin-B and cathepsin-D) were significantly (Plysosomal fraction. The pretreatment with p-coumaric acid significantly (Plysosomal lipid peroxidation products and the activities of lysosomal enzymes. In addition, p-coumaric acid greatly reduced myocardial infarct size. p-Coumaric acid pretreatment (8 mg/kg body weight) to normal rats did not show any significant effect. Thus, this study showed that p-coumaric acid prevents lysosomal dysfunction against cardiac damage induced by isoproterenol and brings back the levels of lipid peroxidation products and activities of lysosomal enzymes to near normal levels. The in vitro study also revealed the free radical scavenging activity of p-coumaric acid. Thus, the observed effects are due to p-coumaric acid's free radical scavenging and membrane stabilizing properties.

  19. Antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models.

    Science.gov (United States)

    Hajhashemi, V; Dehdashti, Kh

    2014-01-01

    Glutamate has a key role in pain perception and also development of tolerance and dependence to morphine. It has been reported that clavulanic acid affects glutamatergic transmission via activation of glutamate transporter. Therefore the present study was aimed to evaluate the possible antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models. Male Swiss mice (25-30 g) were used in this study. Acetic acid-induced writhing, formalin test and hot plate method were used to assess the antinociceptive effect of clavulanic acid. Morphine (30 mg/kg, s.c.) was administered to the mice two times a day (8 AM and 4 PM) for 3 days in order to produce tolerance. To develop morphine dependence, morphine sulfate (50, 50 and 75 mg/kg) was injected at 8 and 12 AM and 16 PM respectively and for 3 consecutive days. Naloxone (5 mg/kg, i.p) was used to induce morphine withdrawal syndrome and the number of jumps and presence of ptosis, piloerection, tremor, sniffing and diarrhea were recorded and compared with control group. Clavulanic acid at doses of 10, 20 and 40 mg/kg inhibited abdominal constriction and licking behavior of acetic acid and formalin-induced pain respectively. Clavulanic acid was not able to show any antinociception in hot plate model and could not prevent development of tolerance and dependence to morphine. Clavulanic acid has considerable antinociceptive activity and further studies are needed to clarify its exact mechanism.

  20. Ovariectomy attenuates dendritic growth in hormone-sensitive spinal motoneurons.

    Science.gov (United States)

    Hebbeler, S L; Verhovshek, T; Sengelaub, D R

    2001-09-15

    The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). Dendritic development of SNB motoneurons in male rats is biphasic, initially showing exuberant growth through 4 weeks of age followed by a retraction to mature lengths by 7 weeks of age. The initial growth is steroid dependent, attenuated by castration or aromatase inhibition, and supported by hormone replacement. Dendritic retraction is also steroid sensitive and can be prevented by testosterone treatment, but is unaffected by aromatase inhibition. Together, these results suggest a role for estrogens during the initial growth phase of SNB development. In this study, we tested whether ovarian hormones could support SNB somal and dendritic development. Motoneuron morphology was assessed in normal males and in females perinatally masculinized with dihydrotestosterone and then either ovariectomized or left intact. SNB motoneurons were retrogradely labeled with cholera toxin-HRP at 4 or 7 weeks of age and reconstructed in three dimensions. Initial growth of SNB dendrites was reduced after ovariectomy in masculinized females. However, no differences in dendritic length were seen at 7 weeks of age between intact and ovariectomized masculinized females, and lengths in both groups were significantly lower than those of normal males. Together with previous findings, these results suggest that estrogens are involved in the early growth of SNB dendrites, but not in their subsequent retraction.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Effect of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits

    Institute of Scientific and Technical Information of China (English)

    LIU Li-min; SONG Yue-ming; DUAN Hong; DING Yong-li; LU Bing

    2006-01-01

    Objective: To determine the efficacy of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits.Methods: Twenty-four apanese white rabbits underwent laminectomy (including the attached ligaments)at L2 and Ls. After laminectomy at L5, polylactic acid glue was sprayed on the dura and nerve roots and this segment was taken as the experimental group. After laminectomy at L2 , nothing was used and this segment was enrolled as the self control group. Four rabbits were killed every two weeks postoperatively till the end of the experiment at 12weeks. Then the operated spine was observed grossly,histologically and ultrastructurally to check the degree of scar formation, the status of epidural scar adhesion, the absorption of the glue, and the intracellular structure of fibroblasts.Results: The glue coagulated immediately after spraying and showed excellent hemostatic effect. The glue membrane was easy to be taken away from the dura mater of the samples for 2 weeks and there were no cells in the epidural space in the experimental group. But the dura mater was covered by hematoma in the control group,which formed mild adhesion, with fibroblasts proliferating actively. In the 4th week, some glue shivers remained in the epidural space with fibroblasts increasing a little, and the dura mater was smooth in the experimental group.However, in the control group, the formed scar was fragile and conglutinated with the dura mater diffusely and fibroblasts were much more than those in the experimental group. In the 6th-12th weeks, there was a potential interspace between the scar and the dura mater, and the polylactic acid glue was absorbed completely in the experimental group. Much tough scar was found in the control group, which was very difficult to dissect from the dura mater and the surrounding tissues. From the ultrastructural observation of the fibroblasts, the nucleus became much bigger and the rough endoplasmic reticulum was much more plentiful in

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

    OpenAIRE

    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...

  4. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

    Science.gov (United States)

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  5. Phase field modeling of dendrite growth

    Institute of Scientific and Technical Information of China (English)

    Yutuo ZHANG; Chengzhi WANG; Dianzhong LI; Yiyi LI

    2009-01-01

    Single dendrite and multi-dendrite growth for A1-2 mol pct Si alloy during isothermal solidification are simulated by phase field method. In the case of single equiaxed dendrite growth, the secondary and the necking phenomenon can be observed. For multi-dendrite growth, there exists the competitive growth among the dendrites dur-ing solidification. As solidification proceeds, growing and coarsening of the primary arms occurs, together with the branching and coarsening of the secondary arms.When the diffusion fields of dendrite tips come into contact with those of the branches growing from the neighboring dendrites, the dendrites stop growing and being to ripen and thicken.

  6. Folic Acid Protected Neural Cells Against Aluminum-Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation.

    Science.gov (United States)

    Zhu, Mingming; Li, Bingfei; Ma, Xiao; Huang, Cong; Wu, Rui; Zhu, Weiwei; Li, Xiaoting; Liang, Zhaofeng; Deng, Feifei; Zhu, Jianyun; Xie, Wei; Yang, Xue; Jiang, Ye; Wang, Shijia; Wu, Jieshu; Geng, Shanshan; Xie, Chunfeng; Zhong, Caiyun; Liu, Haiyan

    2016-08-01

    Aluminum (Al)-induced apoptosis is considered as the major cause of its neurotoxicity. Folic acid possesses neuroprotective function by preventing neural cell apoptosis. microRNAs (miRNAs) are important regulators of gene expression participating in cellular processes. As a key component of the miR-17-92 cluster, miR-19 is implicated in regulating apoptotic process, while its role in the neuroprotective effect of folic acid has not been investigated. The present study aimed to investigate the potential involvement and function of miR-19 in the protective action of folic acid against Al-induced neural cell apoptosis. Human SH-SY5Y cells were treated with Al-maltolate (Al-malt) in the presence or absence of folic acid. Results showed that Al-malt-induced apoptosis of SH-SY5Y cells was effectively prevented by folic acid. Al-malt suppressed the expression of miR-19a/19b, along with alterations of miR-19 related apoptotic proteins including PTEN, p-AKT, p53, Bax, Bcl-2, caspase 9 and caspase 3; and these effects were ameliorated by folic acid. miR-19 inhibitor alone induced apoptosis of SH-SY5Y cells. Combination treatment of folic acid and miR-19 inhibitor diminished the neuroprotective effect of folic acid. These findings demonstrated that folic acid protected neuronal cells against Al-malt-induced apoptosis by preventing the downregulation of miR-19 and modulation of miR-19 related downstream PTEN/AKT/p53 pathway.

  7. [Attitudes of pregnant Japanese women and folic acid intake for the prevention of neural tube defects: a nationwide Internet survey].

    Science.gov (United States)

    Sato, Yoko; Nakanishi, Tomoko; Chiba, Tsuyoshi; Umegaki, Keizo

    2014-01-01

    Folic acid intake is recommended for pregnant women because it significantly reduces the risk of neural tube defects (NTD) in the fetus. However, the risk of NTD remains medium in Japan. In this study, the attitudes of pregnant Japanese women and factors related to folic acid intake for the prevention of NTD were evaluated using a nationwide survey. An Internet-based questionnaire was conducted on 2,367 pregnant Japanese women who were registrants of a Japanese social research company in January 2012; 1,236 of these women responded. In the questionnaires, the knowledge regarding the folate intake (i.e., name of folic acid, the risk of NTD, recommended doses, and timing), actual intake of folic acid, demographic factors (i.e., age, geographical area, gestational age, and birth order), and intake of dietary supplements were surveyed. Eighty-five percent of respondents consumed folate, which was mostly obtained through dietary folic acid supplements during the first month of pregnancy or after. Factors associated with loss of folic acid intake until 3 months of pregnancy included lack of knowledge, failure to consume dietary supplements, younger age, and multigravida. Many pregnant women in Japan consumed folic acid. However, most of them started supplementation after pregnancy recognition, which is too late to reduce the risk of NTD. Alternative strategies to increase the efficacy of folic acid intake, such as recommending folic acid-enriched foods, promoting folic acid fortification efforts, and providing access to practical information, are necessary.

  8. Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro.

    Science.gov (United States)

    Elbaz, Alexandre; Wu, Xiying; Rivas, Daniel; Gimble, Jeffrey M; Duque, Gustavo

    2010-04-01

    Although increased bone marrow fat in age-related bone loss has been associated with lower trabecular mass, the underlying mechanism responsible remains unknown. We hypothesized that marrow adipocytes exert a lipotoxic effect on osteoblast function and survival through the reversible biosynthesis of fatty acids (FA) into the bone marrow microenvironment. We have used a two-chamber system to co-culture normal human osteoblasts (NHOst) with differentiating pre-adipocytes in the absence or presence of an inhibitor of FA synthase (cerulenin) and separated by an insert that allowed unidirectional trafficking of soluble factors only and prevented direct cell-cell contact. Supernatants were assayed for the presence of FA using mass spectophotometry. After 3 weeks in co-culture, NHOst showed significantly lower levels of differentiation and function based on lower mineralization and expression of alkaline phosphatase, osterix, osteocalcin and Runx2. In addition, NHOst survival was affected by the presence of adipocytes as determined by MTS-formazan and TUNEL assays as well as higher activation of caspases 3/7. These toxic effects were inhibited by addition of cerulenin. Furthermore, culture of NHOst with either adipocyte-conditioned media alone in the absence of adipocytes themselves or with the addition of the most predominant FA (stearate or palmitate) produced similar toxic results. Finally, Runx2 nuclear binding was affected by addition of either adipocyte conditioned media or FA into the osteogenic media. We conclude that the presence of FA within the marrow milieu can contribute to the age-related changes in bone mass and can be prevented by the inhibition of FA synthase.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Comparison of 4 % icodextrin and omega 3 Fatty acids in prevention of peritoneal adhesions.

    Science.gov (United States)

    Karakas, Dursun Ozgur; Yigitler, Cengizhan; Gulec, Bulent; Kucukodaci, Zafer; Ipcioglu, Osman Metin; Akin, Mehmet Levhi

    2014-06-01

    Postoperative peritoneal adhesions are major concerns in abdominal surgery. In this experimental study, the effects of 4 % icodextrin and omega-3 fatty acids (ω-3 FA) on prevention of postoperative peritoneal adhesions were evaluated. Twenty-four Wistar albino rats were divided into three groups. After laparotomy, serosal abrasion was carried out by cecal brushing. Intraperitoneally 3 cm(3) 0.9 % NaCl, 3 cm(3) 4 % icodextrin, and 200 mg/kg ω-3 FAs for each group were applied, and then the abdomen was closed. All subjects sacrificed 10 days postoperatively. Macroscopic and histopathological cellular reactions as a function of giant cell, lymphocyte/plasmocyte, neutrophil, histiocyte, intracellular adhesion molecule-1 (ICAM-1), and platelet endothelial cell adhesion molecule-1 (PECAM-1) were assessed and hydroxyproline levels were measured in all three groups and compared using Kruskal-Wallis and ANOVA tests when appropriate. Macroscopically, both ω-3 FAs and 4 % icodextrin reduced adhesion formation but the difference was not statistically significant (P = 0.253). Histopathological examination revealed that there was no statistical significance in terms of giant cell, lymphocyte/plasmocyte, neutrophil, ICAM-1, and PECAM-1 scores; however, both ω-3 FAs and 4 % icodextrin were found to be prone to reduce fibrosis (P = 0.047), whereas in the ω-3 FA group, histiocytic reaction was significantly increased (P = 0.001), and hydroxyproline levels were significantly lower than other groups (P = 0.044). In this study, ω-3 FAs were found to be superior to 4 % icodextrin with the lower hydroxyproline level and greater histiocytic reaction. Considering these results, ω-3 FAs can be a promising agent in the prevention of adhesion formation.

  11. Hyaluronic acid and oxidized regenerated cellulose prevent adhesion reformation after adhesiolysis in rat models.

    Science.gov (United States)

    Zhang, Yan; Liu, Qin; Yang, Ning; Zhang, Xuegang

    2016-01-01

    Postsurgical adhesion formation is the most common complication in abdominal and pelvic surgery. Adhesiolysis is the most commonly applied treatment for adhesion formation but is often followed by adhesion reformation. Therefore, an efficient strategy should be adopted to solve these problems. This study aimed to explore whether hyaluronic acid and oxidized regenerated cellulose (ORC) could prevent adhesion formation and reformation. Thirty female Sprague Dawley rats were randomly divided into three groups (n=10 each) and subjected to different treatments during the first and second surgery. The control group was treated with isotonic sodium chloride, the ORC group was treated with ORC (1.5×1 cm), and the medical sodium hyaluronate (MSH) group was treated with 1% MSH (0.5 mL). At 2 weeks after the first surgery, adhesion scores in the MSH group (1.90±0.99) and the ORC group (1.40±0.97) were significantly lower than those in the control group (3.00±0.82) (P=0.005). Similarly, 2 weeks after the second surgery, adhesion scores in the MSH group (2.00±0.82) and the ORC group (1.50±1.27) were significantly lower than those in the control group (3.50±0.53) (P=0.001). In addition, body weights in the MSH group and the ORC group did not change significantly, whereas the control group showed a consistent decrease in body weight during the experiment. Histological examination revealed that inflammatory infiltration was involved in both adhesion formation and reformation. In conclusion, hyaluronic acid and ORC were both efficient in reducing adhesion formation and reformation in the rat model.

  12. Knowledge and practice of urban Iranian pregnant women towards folic acid intake for neural tube defect prevention.

    Science.gov (United States)

    Nosrat, Sepideh Bakhshande; Sedehi, Maliheh; Golalipour, Mohammad Jafar

    2012-08-01

    To assess the knowledge and practice of urban Iranian pregnant women regarding periconceptional folic acid intake for neural tube defect (NTD) prevention. The population-based study was done on 676 primiparous women in an urban area in Golestan province in northern Iran from June to November, 2008. A questionnaire was completed by the subjects regarding their knowledge of folic acid. Questionnaires were administered to women who were seeking routine antenatal care at health centres, private gynaecological clinic and the Dezyani Gynaecologic and Obstetric Hospital. Questions covered knowledge and use of folic acid supplements and demographic and socioeconomic characteristics. Out of the 676 women surveyed, 96.2% reported that they heard of folate. Of these, only 27.6% knew that folate was something important in the prevention of neural tube defects. Overall, 20.12% of the total women took folic acid during periconceptional period. The most common information sources on folate were healthcare service (54.5%). Besides, 37.6% of the subjects who heard about folate were aware that green leafy vegetables were fortified with folic acid. In univariate analysis, knowledge and intake of folic acid was not associated with education and the age of women. A healthcare plan for intervention to increase the knowledge and intake of folic acid by pregnant women during the protective period is required.

  13. Folic acid and prevention of neural tube defects in 2000 improved awareness--low peri-conceptional uptake.

    Science.gov (United States)

    Oleary, M; Donnell, R M; Johnson, H

    2001-06-01

    Eight years have passed since recommendations were made by the Irish Department of Health on the importance of folic acid in the prevention of neural tube defects (NTD). There is currently no mandatory fortification of foodstuffs with folic acid in Ireland, with reliance placed on campaigns promoting increased dietary folate intake and supplements. We assessed knowledge and use of folic acid among 300 women attending ante-natal clinics in Dublin maternity hospitals in the year 2000 using an interviewer administered questionnaire. Qualitative information was obtained through means of a focus group. Ninety two percent of respondents had heard of folic acid and 67% knew it could prevent NTD. Thirty per cent were advised to take it peri-conceptionally but overall only 18% did so; 39% of women had planned their pregnancy. The focus group indicated that folic acid was not 'visible' enough and that fortification of food was more realistic. This study shows that improved folic acid awareness has not been accompanied by corresponding peri-conceptional uptake in 2000. Folic acid promotional campaigns should be continuous and targeted. Mandatory food fortification should be strongly considered.

  14. 靶向乳腺癌干细胞树突细胞瘤苗核酸抗原的制备%Preparation of mucleic acid antigen for dendritic cell vaccine targeting on breast cancer stem cell

    Institute of Scientific and Technical Information of China (English)

    谢云青; 郑秋红; 应敏刚; 刘健

    2012-01-01

    The study was to enrich MCF 7 breast cancer stem cells by mammosphere culture using serum free mediumand prepare mRNA nucleic acid antigen for preparation of dendritic cell vaccine targeting on breast cancer stem cell. MCF 7 breast cancer stem cell was cultured and enriched by using serum free medium, and confirmed by identification of cellular sur face marks by using flow cytometer, clone forming capability test by agar assay, and tumorigenic ability test in vivo by using NOD SCID mouse. The mRNA was amplified by using T7 mMESSAGE mMACHINE kit with template of total RNA extracted from MCF 7 breast cancer stem cells. The result showed that MCF 7 breast cancer cell grouped and formed mammosphere in cultural suspension by using serum free media. About 90. 16% cells within mammosphere possessed CD+44/CD-24 phenotype. The ability of clone forming and capability of tumor initiating in NOD/SCID mouse with low dose were stronger in suspension cells than that in adhesive cells. The mRNA molecule amplified in vitro could be as specific nucleic acid antigen of breast cancer stem cells. We proposed that the high percent of MCF 7 breast cancer stem cells could be obtained by mammosphere culture u sing serum free medium, and mRNA amplified in vitro could be as specific nucleic acid antigen of breast cancer stem cells. It lay a foundation for preparation of dendritic cell vaccine targeting on breast cancer stem cell.%目的 应用无血清培养基细胞球培养法富集MCF-7乳腺癌千细胞,制备乳腺癌干细胞mRNA核酸抗原,为制备靶向乳腺癌干细胞树突细胞瘤苗奠定基础.方法 应用无血清培养基悬浮培养法富集MCF-7乳腺癌细胞,经单克隆形成、表面标志检测、NOD-SCID小鼠成瘤等实验对其肿瘤干细胞特性进行鉴定后,利用T7 mMESSAGE mMACHINE试剂盒进行mRNA体外扩增.结果 乳腺癌细胞MCF-7在无血清培养基中可形成悬浮状细胞球,其中具有CD44+CD24-表面标志的细胞约占90.16%.该细

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

    Science.gov (United States)

    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...

  16. Folic acid supplementation in pregnancy to prevent preterm birth: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Saccone, Gabriele; Berghella, Vincenzo

    2016-04-01

    Folic acid (FA) may have a role in the prevention of pregnancy complications. However, the efficacy of FA supplementation in reducing the risk of preterm birth (PTB) is still unclear. The aim of this systematic review with meta-analysis was to evaluate the efficacy of folic acid supplementation during pregnancy to prevent preterm birth (PTB). The research protocol was designed a priori, defining methods for searching the literature in electronic databases, including and examining articles, and extracting and analyzing data. We included all randomized trials (RCTs) of asymptomatic singleton gestations without prior PTB who were randomized to prophylactic treatment with either FA supplementation or control (placebo or no treatment). The primary outcome was the incidence of PTB pregnancy does not prevent PTB <37 weeks. Daily FA supplementation remains the most important intervention to reduce the risk of neural tube defects.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  18. Resveratrol prevents social deficits in animal model of autism induced by valproic acid.

    Science.gov (United States)

    Bambini-Junior, Victorio; Zanatta, Geancarlo; Della Flora Nunes, Gustavo; Mueller de Melo, Gabriela; Michels, Marcus; Fontes-Dutra, Mellanie; Nogueira Freire, Valder; Riesgo, Rudimar; Gottfried, Carmem

    2014-11-07

    Autism spectrum disorders (ASD) involve a complex interplay of both genetic and environmental risk factors, such as prenatal exposure to valproic acid (VPA). Considering the neuroprotective, antioxidant and anti-inflammatory effects of resveratrol (RSV), we investigated the influence of prenatal RSV treatment on social behaviors of a rodent model of autism induced by prenatal exposure to VPA. In the three-chambered apparatus test, the VPA group showed a reduced place preference conditioned by conspecific and no preference between exploring a wire-cage or a rat enclosed inside a wire cage, revealing sociability impairments. Prenatal administration of RSV prevented the VPA-induced social impairments evaluated in this study. A bioinformatics analysis was used to discard possible molecular interactions between VPA and RSV during administration. The interaction energy between RSV and VPA is weak and highly unstable, suggesting cellular effects instead of a single chemical process. In summary, the present study highlights a promising experimental strategy to evaluate new molecular targets possibly involved in the etiology of autism and developmental alterations implicated in neural and behavioral impairments in ASD.

  19. Salicylic acid prevents Trichoderma harzianum from entering the vascular system of roots.

    Science.gov (United States)

    Alonso-Ramírez, Ana; Poveda, Jorge; Martín, Ignacio; Hermosa, Rosa; Monte, Enrique; Nicolás, Carlos

    2014-10-01

    Trichoderma is a soil-borne fungal genus that includes species with a significant impact on agriculture and industrial processes. Some Trichoderma strains exert beneficial effects in plants through root colonization, although little is known about how this interaction takes place. To better understand this process, the root colonization of wild-type Arabidopsis and the salicylic acid (SA)-impaired mutant sid2 by a green fluorescent protein (GFP)-marked Trichoderma harzianum strain was followed under confocal microscopy. Trichoderma harzianum GFP22 was able to penetrate the vascular tissue of the sid2 mutant because of the absence of callose deposition in the cell wall of root cells. In addition, a higher colonization of sid2 roots by GFP22 compared with that in Arabidopsis wild-type roots was detected by real-time polymerase chain reaction. These results, together with differences in the expression levels of plant defence genes in the roots of both interactions, support a key role for SA in Trichoderma early root colonization stages. We observed that, without the support of SA, plants were unable to prevent the arrival of the fungus in the vascular system and its spread into aerial parts, leading to later collapse.

  20. Prevention of Polyglycolic Acid-Induced Peritoneal Adhesions Using Alginate in a Rat Model

    Directory of Open Access Journals (Sweden)

    Mari Matoba

    2015-01-01

    Full Text Available Postoperative intra-abdominal or intrathoracic adhesions sometimes cause significant morbidity. We have designed three types of alginate-based treatments using strongly cross-linked (SL, weakly cross-linked (WL, and non-cross-linked (NL alginate with calcium gluconate. In rat experiments, we compared the antiadhesive effects of the three types of alginate-based treatments, fibrin glue treatment (a standard treatment, and no treatment against adhesions caused by polyglycolic acid (PGA mesh (PGA-induced adhesions. The antiadhesive materials were set on the PGA sheet fixed on the parietal peritoneum of the abdomen. Fifty-six days later, the adhesions were evaluated macroscopically by the adhesion scores and microscopically by hematoxylin-eosin staining and immunostaining. We also tested the fibroblast growth on the surface of the antiadhesive materials in vitro. The antiadhesive effects of WL and NL were superior to the no treatment and fibrin glue treatment. A microscopic evaluation confirmed that the PGA sheet was covered by a peritoneal layer constructed of well-differentiated mesothelial cells, and the inflammation was most improved in the NL and WL. The fibroblast growth was inhibited most on the surfaces of the NL and WL. These results suggest that either the WL or NL treatments are suitable for preventing PGA-induced adhesions compared to SL or the conventional treatment.

  1. Awareness and intake of folic acid for the prevention of neural tube defects among Lebanese women of childbearing age.

    Science.gov (United States)

    Nasr Hage, Claudine; Jalloul, Maya; Sabbah, Mohamad; Adib, Salim M

    2012-01-01

    Since the early 1990s, international recommendations have promoted folic acid supplementation during the periconception period as an effective way of preventing neural tube defects (NTDs). However, the adoption of this recommendation remains insufficient. To assess the awareness and actual intake of folic acid among married Lebanese women aged 18-45 years, a cross-sectional study was conducted among 600 women selected from all five administrative districts in Lebanon, using a multistage cluster sampling procedure. An anonymous questionnaire was completed which covered measures of knowledge and use of folate supplements, as well as demographic, socioeconomic and obstetrical factors. Sixty percent of surveyed women (60%; n = 360) had heard about folic acid. Doctors were the most frequent source of information (61.1%) but only 24.7% of women have been told of the correct period during which folic acid supplementation was useful. Overall, only 6.2% had taken folic acid tablets during the adequate period. Younger age, higher education level and stability/sufficiency of income appeared to be significant predictors of awareness among Lebanese women. Actual folic acid intake was significantly associated with younger age, higher number of pregnancies, planning the last pregnancy and having had that last one after 1990. In Lebanon, the level of folic acid awareness and adequate intake remain relatively low. Several approaches should be used to promote folic acid intake including awareness campaigns, and routine counseling by primary health care physicians on folic acid during preconception visits.

  2. Viruses, dendritic cells and the lung

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 利用RelB小干扰RNA沉默的树突状细胞预防急性排斥反应%Prevention of acute rejection by RelB siRNA-silenced dendritic cells

    Institute of Scientific and Technical Information of China (English)

    邱涛; 祝恒成; 刘修恒; 胡春海

    2013-01-01

    Objective To prevente acute rejection in cardiac transplantation by using tolerogenic dendritic cells (DC).Methods The mixed lymphocyte reaction (MLR) was performed by RelB siRNA-DC with allogenic antigen-specific T cells.The apoptosis rate of T cells and the ratio of CD4 + CD25 + Foxp3 + regulatory T cells were detected by using flow cytometry after MLR.In the murine model of cardiac transplantation,the survival time was observed after infusion of RelB siRNA-DC before transplantation.HE staining was used to examine the rejection degree in the specimens of allografts.Results Mature DC and LucR siRNA DC could stimulate the proliferation of T cells more strongly than immature DC and RelB siRNA-DC (P < 0.05).The RelB siRNA-DC could induce allogeneic T cell hyporesponsiveness,but had no specific reactivity on the third kind T cells (P > 0.05).RelB siRNA-DC induced T cell apoptosis [(29.21 ± 7.55)%,P < 0.05] and promoted T cells differentation into CD4 + CD25 + Foxp3 + regulatory T cells [(65.3 ± 12.6)%,P < 0.05].In the mouse cardiac transplantation model,infusion of donor-derived Lenti-RelB siRNA-DC could prolong the graft survival time (P < 0.05) and reduce rejection occurrence.Conclusion Donor-derived RelB-siRNA-induced tolerogenic DC can significantly induce immune tolerance in vitro and in vivo.%目的 利用RelB小干扰RNA (siRNA)沉默的树突状细胞(DC)预防心脏移植排斥反应.方法 RelB siRNA-DC同同种抗原特异性T细胞进行混合淋巴细胞反应,检测反应后T细胞凋亡率及CD4+ CD25+叉状头/翅膀状螺旋转录因子(Foxp3)+调节性T细胞的比率;利用小鼠心脏移植模型,于移植前输注各组DC,观察移植后小鼠心脏存活时间;苏木素-伊红(HE)染色检测排斥反应程度.结果 较其他3组DC,RelB siRNA组DC刺激同种T细胞增殖能力明显减弱(P<0.05);但对第3方抗原T细胞无特异性低反应性(P>0.05);RelB siRNA-DC诱导T细胞凋亡率增加(29.21±7.55)

  5. Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer's disease--but how and why?

    Science.gov (United States)

    Das, Undurti N

    2008-01-01

    Low blood folate and raised homocysteine concentrations are associated with poor cognitive function. Folic acid supplementation improves cognitive function. Folic acid enhances the plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). EPA, DHA, and arachidonic acid (AA) are of benefit in dementia and Alzheimer's disease by up-regulating gene expression concerned with neurogenesis, neurotransmission and connectivity, improving endothelial nitric oxide (eNO) generation, enhancing brain acetylcholine levels, and suppressing the production of pro-inflammatory cytokines. EPA, DHA, and AA also form precursors to anti-inflammatory compounds such as lipoxins, resolvins, and neuroprotectin D1 (NPD1) that protect neurons from the cytotoxic action of various noxious stimuli. Furthermore, various neurotrophins and statins enhance the formation of NPD1 and thus, protect neurons from oxidative stress and prevent neuronal apoptosis Folic acid improves eNO generation, enhances plasma levels of EPA/DHA and thus, could augment the formation of NPD1. These results suggest that a combination of EPA, DHA, AA and folic acid could be of significant benefit in dementia, depression, and Alzheimer's disease and improve cognitive function.

  6. Reactivity of chemical sensitizers toward amino acids in cellulo plays a role in the activation of the Nrf2-ARE pathway in human monocyte dendritic cells and the THP-1 cell line.

    Science.gov (United States)

    Migdal, Camille; Botton, Jérémie; El Ali, Zeina; Azoury, Marie-Eliane; Guldemann, Joan; Giménez-Arnau, Elena; Lepoittevin, Jean-Pierre; Kerdine-Römer, Saadia; Pallardy, Marc

    2013-06-01

    Allergic contact dermatitis resulting from skin sensitization is an inflammatory skin disease linked to the use of chemicals termed haptens. Chemical reactivity is necessary for a chemical to be a sensitizer, allowing both covalent binding to proteins and maturation of dendritic cells (DCs) by mimicking "danger signals." The aim of this study was to evaluate how the reactivity of chemical sensitizers toward amino acids translates into a biological response using the activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway, which was assessed by the induction of three Nrf2 target genes (ho-1, nqo1, and il-8) and Nrf2 protein accumulation. Nrf2 activation is known to play a role in numerous detoxification mechanisms that could regulate danger signal outcomes in myeloid cells. Monocyte-derived DCs and THP-1 cells were exposed to (a) haptens with cysteine, lysine, or cysteine/lysine reactivity, (b) pro-/prehaptens, and (c) nonsensitizing molecules with reducing or oxidative properties (17 molecules in total). Chemicals were classified as "Nrf2 pathway activators" when at least two Nrf2 target genes associated with Nrf2 protein expression were induced. Results showed that most chemical sensitizers having cysteine and cysteine/lysine affinities were inducers of the Nrf2 pathway in both cell models, whereas lysine-reactive chemicals were less efficient. In THP-1 cells, the Nrf2 pathway was also activated by pro-/prehaptens. Regression analysis revealed that ho-1 and nqo1 expressions were found to be associated with chemical sensitizer reactivity to cysteine, providing evidence of the importance of chemical reactivity, as a part of danger signals, in DC biology.

  7. Efficacy of Poly(D,L-Lactic Acid-co-Glycolic acid)-Poly(Ethylene Glycol)-Poly(D,L-Lactic Acid-co-Glycolic Acid) Thermogel As a Barrier to Prevent Spinal Epidural Fibrosis in a Postlaminectomy Rat Model.

    Science.gov (United States)

    Li, Xiangqian; Chen, Lin; Lin, Hong; Cao, Luping; Cheng, Ji'an; Dong, Jian; Yu, Lin; Ding, Jiandong

    2017-04-01

    Experimental animal study. The authors conducted a study to determine the efficacy and safety of the poly(D,L-lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) thermogel to prevent peridural fibrosis in an adult rat laminectomy model. Peridural fibrosis often occurs after spinal laminectomy. It might cause persistent back and/or leg pain postoperatively and make a reoperation more difficult and dangerous. Various materials have been used to prevent epidural fibrosis, but only limited success has been achieved. The PLGA-PEG-PLGA thermogel was synthesized by us. Total L3 laminectomies were performed on 24 rats. The PLGA-PEG-PLGA thermogel or chitosan (CHS) gel (a positive control group) was applied to the operative sites in a blinded manner. In the control group, the L3 laminectomy was performed and the defect was irrigated with the NS solution 3 times. All the rats were killed 4 weeks after the surgery. The cytotoxicity of this thermogel was evaluated in vitro and the result demonstrated that no evidence of cytotoxicity was observed. The extent of epidural fibrosis, the area of epidural fibrosis, and the density of the fibroblasts and blood vessel were evaluated histologically. There were statistical differences among the PLGA-PEG-PLGA thermogel or CHS gel group compared with the control group. Although there was no difference between the PLGA-PEG-PLGA thermogel and CHS gel, the efficiency of the PLGA-PEG-PLGA thermogel was shown to be slightly improved compared with the CHS gel. The biocompatibility of the PLGA-PEG-PLGA thermogel was proven well. The application of this thermogel effectively reduced epidural scarring and prevented the subsequent adhesion to the dura mater. No side effects were noted in the rats.

  8. Novel biodegradable α-TCP/poly(amino acid) composite artificial lamina following spinal surgery for prevention of intraspinal scar adhesion.

    Science.gov (United States)

    Ran, Bo; Song, Yue-Ming; Liu, Hao; Liu, Li-Min; Gong, Quan; Li, Tao; Zeng, Jian-Cheng; Yuan, Hai-Feng

    2011-12-01

    Biodegradable copolymer α-TCP/poly(amino acid) composite artificial lamina was prepared and used in goat cervical vertebra resection repair. Cervical 4 was removed by laminectomy, and a vertebra defect of 27 × 9 mm was made. α-TCP/poly(amino acid) composite artificial lamina was inserted in the test group. The efficiency of the copolymer during repair and reconstruction of the goats' vertebra was tested by using X-ray, CT scanning, and histological and biomechanical measurements. In the 24 weeks following the operation, the artificial lamina refrained from shifting, and no dural adhesion pressure was observed. In contrast, the control group suffered from infiltration of soft tissue in the spinal canal, dural pressure and α-TCP/poly(amino acid) degradation. In conclusion, α-TCP/poly(amino acid) composite artificial lamina can significantly prevent scar tissue from infiltrating the spinal canal.

  9. Dendrite Injury Triggers DLK-Independent Regeneration

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    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.

  10. Comparison between conjugated linoleic acid and essential fatty acids in preventing oxidative stress in bovine mammary epithelial cells.

    Science.gov (United States)

    Basiricò, L; Morera, P; Dipasquale, D; Tröscher, A; Bernabucci, U

    2017-03-01

    Some in vitro and in vivo studies have demonstrated protective effects of conjugated linoleic acid (CLA) isomers against oxidative stress and lipid peroxidation. However, only a few and conflicting studies have been conducted showing the antioxidant potential of essential fatty acids. The objectives of the study were to compare the effects of CLA to other essential fatty acids on the thiol redox status of bovine mammary epithelia cells (BME-UV1) and their protective role against oxidative damage on the mammary gland by an in vitro study. The BME-UV1 cells were treated with complete medium containing 50 μM of cis-9,trans-11 CLA, trans-10,cis-12 CLA, α-linolenic acid, γ-linolenic acid, and linoleic acid. To assess the cellular antioxidant response, glutathione, NADPH, and γ-glutamyl-cysteine ligase activity were measured 48 h after addition of fatty acids (FA). Intracellular reactive oxygen species and malondialdehyde production were also assessed in cells supplemented with FA. Reactive oxygen species production after 3 h of H2O2 exposure was assessed to evaluate and to compare the potential protection of different FA against H2O2-induced oxidative stress. All FA treatments induced an intracellular GSH increase, matched by high concentrations of NADPH and an increase of γ-glutamyl-cysteine ligase activity. Cells supplemented with FA showed a reduction in intracellular malondialdehyde levels. In particular, CLA isomers and linoleic acid supplementation showed a better antioxidant cellular response against oxidative damage induced by H2O2 compared with other FA. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  13. Palmitoleic acid prevents palmitic acid-induced macrophage activation and consequent p38 MAPK-mediated skeletal muscle insulin resistance.

    Science.gov (United States)

    Talbot, Nicola A; Wheeler-Jones, Caroline P; Cleasby, Mark E

    2014-08-05

    Obesity and saturated fatty acid (SFA) treatment are both associated with skeletal muscle insulin resistance (IR) and increased macrophage infiltration. However, the relative effects of SFA and unsaturated fatty acid (UFA)-activated macrophages on muscle are unknown. Here, macrophages were treated with palmitic acid, palmitoleic acid or both and the effects of the conditioned medium (CM) on C2C12 myotubes investigated. CM from palmitic acid-treated J774s (palm-mac-CM) impaired insulin signalling and insulin-stimulated glycogen synthesis, reduced Inhibitor κBα and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase in myotubes. p38 MAPK inhibition or siRNA partially ameliorated these defects, as did addition of tumour necrosis factor-α blocking antibody to the CM. Macrophages incubated with both FAs generated CM that did not induce IR, while palmitoleic acid-mac-CM alone was insulin sensitising. Thus UFAs may improve muscle insulin sensitivity and counteract SFA-mediated IR through an effect on macrophage activation.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Controlled Synthesis of Dendritic Polyaniline Fibers with Diameters from Nanosize to Submicrometersize

    Institute of Scientific and Technical Information of China (English)

    Xiao Cong WANG; Shu Jiang DING; Jing CAO; Fa Lun WU; Chen ZHOU; Zhen Zhong YANG

    2005-01-01

    Dendritic polyaniline nanofibers and submicrometer-sized fibers have been synthesized by chemical oxidative polymerization of aniline (An) doped with salicylic acid (SA). The diameters of the fibers could be controlled easily from 30 to 400 nm by varying the concentration of aniline and salicylic acid at room temperature. Scanning electron microscopy (SEM) and typical transmission electron microscopy (TEM) were applied to investigate their morphologies. Fourier transform infrared (FTIR) spectrum indicated that the state of the dendritic polyaniline fibers is emerialdine rather than solely the leucoemeraldine or permigraniline forms. The dendritic polyaniline fibers have potential applications as chemical sensors or actuators and neuron devices.

  16. All-trans retinoic acid stealth liposomes prevent the relapse of breast cancer arising from the cancer stem cells.

    Science.gov (United States)

    Li, Ruo-Jing; Ying, Xue; Zhang, Yan; Ju, Rui-Jun; Wang, Xiao-Xing; Yao, Hong-Juan; Men, Ying; Tian, Wei; Yu, Yang; Zhang, Liang; Huang, Ren-Jie; Lu, Wan-Liang

    2011-02-10

    The relapse of cancer is mostly due to the proliferation of cancer stem cells which could not be eliminated by a standard chemotherapy. A new kind of all-trans retinoic acid stealth liposomes was developed for preventing the relapse of breast cancer and for treating the cancer in combination with a cytotoxic agent, vinorelbine stealth liposomes. In vitro studies were performed on the human breast cancer MCF-7 and MDA-MB-231 cells. In vivo evaluations were performed on the newly established relapse model with breast cancer stem cells. Results showed that the particle size of all-trans retinoic acid stealth liposomes was approximately 80nm, and the encapsulation efficiency was >90%. Breast cancer stem cells were identified with the CD44(+)/CD24(-) phenotype and characterized with properties: resistant to cytotoxic agent, stronger capability of proliferation, and stronger capability of differentiation. Inhibitory effect of all-trans retinoic acid stealth liposomes was more potent in cancer stem cells than in cancer cells. The mechanisms were defined to be two aspects: arresting breast cancer stem cells at the G(0)/G(1) phase in mitosis, and inducing the differentiation of breast cancer stem cells. The cancer relapse model was successfully established by xenografting breast cancer stem cells into NOD/SCID mice, and the formation and growth of the xenografted tumors were significantly inhibited by all-trans retinoic acid stealth liposomes. The combination therapy of all-trans retinoic acid stealth liposomes with vinorelbine stealth liposomes produced the strongest inhibitory effect to the relapse tumor model. It could be concluded that all-trans retinoic acid stealth liposomes could be used for preventing the relapse of breast cancer by differentiating cancer stem cells and arresting the cell-cycle, and for treating breast cancer as a co-therapy, thus providing a novel strategy for treating breast cancer and preventing relapse derived from breast cancer stem cells.

  17. Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity.

    Science.gov (United States)

    Kaliannan, K; Wang, B; Li, X-Y; Bhan, A K; Kang, J X

    2016-06-01

    Early-life antibiotic exposure can disrupt the founding intestinal microbial community and lead to obesity later in life. Recent studies show that omega-3 fatty acids can reduce body weight gain and chronic inflammation through modulation of the gut microbiota. We hypothesize that increased tissue levels of omega-3 fatty acids may prevent antibiotic-induced alteration of gut microbiota and obesity later in life. Here, we utilize the fat-1 transgenic mouse model, which can endogenously produce omega-3 fatty acids and thereby eliminates confounding factors of diet, to show that elevated tissue levels of omega-3 fatty acids significantly reduce body weight gain and the severity of insulin resistance, fatty liver and dyslipidemia resulting from early-life exposure to azithromycin. These effects were associated with a reversal of antibiotic-induced dysbiosis of gut microbiota in fat-1 mice. These results demonstrate the beneficial effects of omega-3 fatty acids on antibiotic-induced gut dysbiosis and obesity, and suggest the potential utility of omega-3 supplementation as a safe and effective means for the prevention of obesity in children who are exposed to antibiotics.

  18. Folic acid in the prevention of neural tube defects: awareness among laywomen and healthcare providers in Japan.

    Science.gov (United States)

    Kondo, Atsuo; Yamamoto, Shin-ichi; Inoue, Hiromi; Watanabe, Junichiro; Tada, Katsuhiko; Yoshimoto, Nobuko

    2009-09-01

    It is known that neural tube defects are folic acid preventable congenital anomalies. We investigated to what extent this information was disseminated among laywomen and healthcare providers. Questionnaire studies were conducted twice, in 2002 and 2007, for four groups of laywomen and seven groups of healthcare providers in Japan regarding awareness, folic acid supplements and healthy diets. Awareness among laywomen was less than 20%, except for families who had experience with spina bifida in 2002, and 5 years later only pregnant women showed a significant increase in awareness. Awareness among healthcare providers varied from 12 to 76%, depending on their profession, and this proportion increased in five of the seven groups in 2007. The majority of laywomen obtained their information from mass media, while the majority of healthcare providers received information through media for professionals. Laywomen who used folate supplements and healthcare providers who recommended them were initially fewer than 25 and 37%, respectively. Five years later, however, pregnant women who used folic acid supplements increased from 9.1 to 43.1%. As awareness among non-pregnant laywomen and some healthcare providers is considerably low, information should be presented repeatedly to these groups. The difficulty in getting women to consume folic acid supplements is an argument for the government to require folic acid fortification of grains so that the prevention of neural tube defects can be maximized.

  19. Effect of processing on folic acid fortified Baladi bread and its possible effect on the prevention of colon cancer.

    Science.gov (United States)

    Omar, Rasha M; Ismail, Hanaa M; El-Lateef, Bothyna M Abd; Yousef, Mokhtar I; Gomaa, Naglaa F; Sheta, Manal

    2009-07-01

    This paper studied the possible effect of folic acid in fortified Baladi bread on the prevention of colon cancer development in rats. Wheat flour samples (82% extraction rate) and soy bean flour were analyzed to determine their folic acid contents using the High Performance Liquid Chromatography (HPLC). Unfortified and folic acid fortified Baladi breads were prepared. Samples from each step of bread preparation were analyzed for folic acid concentration. Protein, fat, ash, fibers and carbohydrates percentages were also determined. Rats were divided into five groups, four of them were injected subcutaneously with dimethylhydrazine (DMH). After 15 weeks, the rats were sacrificed for pathological examination. Results showed that the folic acid content in wheat flour (82% extraction rate) was found to be highly significantly lower than that in soybean flour. After baking, folic acid content in all breads was found to decrease significantly. The highest protein and fat contents were found in soybean flour fortified Baladi bread. The colons of rats of groups 3 (fed 5% soy flour fortified Baladi bread) and 5 (fed Baladi bread fortified with 5% soy flour+8 mg folic acid/kg wheat flour) were the mostly affected by DMH injection as premalignant changes were observed.

  20. Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages.

    Science.gov (United States)

    Jaber, Lutfi; Karim, Igbaria A; Jawdat, Abu Moch; Fausi, Mawasi; Merlob, Paul

    2004-01-01

    Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50-70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of NTD among Arab Israeli women of childbearing age. We conducted a cross-sectional study. Of the 653 women (18-45 years) who were randomly selected for interview while visiting their family physician or well-baby clinic, 624 women completed the questionnaire. Fifty-three percent (n = 333) of the respondents had heard of folic acid; 14% (n = 89) were familiar with the protective effect of NTD and 3% (n = 18) had taken folic acid in the first months of pregnancy whereas none of them had used it in the preconception period. Highly educated women, women with one or two children, paramedics, and women of high socioeconomic status were more knowledgeable about the protective effects of folic acid (P awareness of this population to the protective effect of folic acid. Daily supplementation and fertification of food with folic acid should be considered as the best way to improve the balance of folic acid in women of childbearing age of this special population (high prevalence of consanguinity).

  1. Knowledge and peri-conceptional use of folic acid in ethnic communities in the UK for the prevention of Neural Tube Defects

    OpenAIRE

    Peake, J; Copp, AJ; Shawe, J

    2013-01-01

    BACKGROUND: It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). METHODS: A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced source...

  2. Ferulic acid prevents methylglyoxal-induced protein glycation, DNA damage, and apoptosis in pancreatic β-cells.

    Science.gov (United States)

    Sompong, Weerachat; Cheng, Henrique; Adisakwattana, Sirichai

    2017-02-01

    Methylglyoxal (MG) can react with amino acids of proteins to induce protein glycation and consequently the formation of advanced glycation end-products (AGEs). Previous studies reported that ferulic acid (FA) prevented glucose-, fructose-, and ribose-induced protein glycation. In this study, FA (0.1-1 mM) inhibited MG-induced protein glycation and oxidative protein damage in bovine serum albumin (BSA). Furthermore, FA (0.0125-0.2 mM) protected against lysine/MG-mediated oxidative DNA damage, thereby inhibiting superoxide anion and hydroxyl radical generation during lysine and MG reaction. In addition, FA did not have the ability to trap MG. Finally, FA (0.1 mM) pretreatment attenuated MG-induced decrease in cell viability and prevented MG-induced cell apoptosis in pancreatic β-cells. The results suggest that FA is capable of protecting β-cells from MG-induced cell damage during diabetes.

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

    Directory of Open Access Journals (Sweden)

    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”.

  4. Optimal Current Transfer in Dendrites

    Science.gov (United States)

    Bird, Alex D.

    2016-01-01

    Integration of synaptic currents across an extensive dendritic tree is a prerequisite for computation in the brain. Dendritic tapering away from the soma has been suggested to both equalise contributions from synapses at different locations and maximise the current transfer to the soma. To find out how this is achieved precisely, an analytical solution for the current transfer in dendrites with arbitrary taper is required. We derive here an asymptotic approximation that accurately matches results from numerical simulations. From this we then determine the diameter profile that maximises the current transfer to the soma. We find a simple quadratic form that matches diameters obtained experimentally, indicating a fundamental architectural principle of the brain that links dendritic diameters to signal transmission. PMID:27145441

  5. Electrical advantages of dendritic spines.

    Directory of Open Access Journals (Sweden)

    Allan T Gulledge

    Full Text Available Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties. We tested this hypothesis using computational models of simplified and morphologically realistic spiny neurons that allow direct comparison of EPSPs generated on spine heads with EPSPs generated on dendritic shafts at the same dendritic locations. In all morphologies tested, spines greatly reduced location-dependent variability of local EPSP amplitude and kinetics, while having minimal impact on EPSPs measured at the soma. Spine-dependent standardization of local EPSP properties persisted across a range of physiologically relevant spine neck resistances, and in models with variable neck resistances. By reducing the variability of local EPSPs, spines standardized synaptic activation of NMDA receptors and voltage-gated calcium channels. Furthermore, spines enhanced activation of NMDA receptors and facilitated the generation of NMDA spikes and axonal action potentials in response to synaptic input. Finally, we show that dynamic regulation of spine neck geometry can preserve local EPSP properties following plasticity-driven changes in synaptic strength, but is inefficient in modifying the amplitude of EPSPs in other cellular compartments. These observations suggest that one function of dendritic spines is to standardize local EPSP properties throughout the dendritic tree, thereby allowing neurons to use similar voltage-sensitive postsynaptic mechanisms at all dendritic locations.

  6. Self-organized dendritic sidebranching in directional solidification: sidebranch coherence within uncorrelated bursts.

    Science.gov (United States)

    Pocheau, Alain; Bodea, Simona; Georgelin, Marc

    2009-09-01

    We experimentally study the level of organization of dendritic sidebranching in directional solidification. For this, we extract successive interface positions at a fixed distance from the dendrite tips and we perform various correlation analyses. The sidebranching signals appear composed of randomly distributed bursts in which sidebranching coherence is surprisingly large and robust. This is attested by the large autocorrelation found in single bursts and the large cross-correlation found in any couple of bursts, even belonging to different sides of a dendrite or to different dendrites. However, the phase coherence of sidebranching breaks down at the transition between bursts. This restricts the coherence of extended sidebranching signals to a mean burst length and prevents the occurrence of large scale cross-correlation between them. This balanced view on sidebranching coherence stresses the capability of self-organization of dendrites in material science and sheds light on the nature of sidebranching on curved growing forms.

  7. The Isothermal Dendritic Growth Experiment

    Science.gov (United States)

    Glicksman, M. E.; Koss, M. B.; Malarik, D. C.

    1998-01-01

    The growth of dendrites is one of the commonly observed forms of solidification encountered when metals and alloys freeze under low thermal gradients, as occurs in most casting and welding processes. In engineering alloys, the details of the dendritic morphology directly relates to important material responses and properties. Of more generic interest, dendritic growth is also an archetypical problem in morphogenesis, where a complex pattern evolves from simple starting conditions. Thus, the physical understanding and mathematical description of how dendritic patterns emerge during the growth process are of interest to both scientists and engineers. The Isothermal Dendritic Growth Experiment (IDGE) is a basic science experiment designed to measure, for a fundamental test of theory, the kinetics and morphology of dendritic growth without complications induced by gravity-driven convection. The IDGE, a collaboration between Rensselaer Polytechnic Institute, in Troy NY, and NASA's Lewis Research Center (LeRC) was developed over a ten year period from a ground-based research program into a space flight experiment. Important to the success of this flight experiment was provision of in situ near-real-time teleoperations during the spaceflight experiment.

  8. Combined application of acellular bovine pericardium and hyaluronic acid in prevention of postoperative pericardial adhesion.

    Science.gov (United States)

    Shen, Jia; Xu, Zhi Wei

    2014-03-01

    An experiment was designed to find the suitable acellular bovine pericardium (ABP) patch in pericardial cavity reconstruction and to evaluate the effect of sodium hyaluronic acid (NaHA) on inflammatory reaction in prevention of pericardial adhesions. The pericardial adhesion model was established in 20 rabbits, weighing from 3.2 to 3.6 kg. Groups were classified as follows: Group A (n = 5), the control group, the pericardium was directly closed; Group B (n = 5), 0.15% glutaraldehyde-treated ABP (low cross-link degree); Group C, 0.3% glutaraldehyde-treated ABP (middle cross-link degree); Group D, 0.15% glutaraldehyde-treated ABP + NaHA solution. Blood samples were collected at 6 h, 24 h, 3 days, and 5 days, to assay postoperative inflammatory reaction. The tenacity and severity of adhesions were evaluated 2 months after operation, by macroscopic and microscopic examinations, and Q-PCR (real-time quantitative polymerase chain reaction) test was used to quantitatively analyze the associated genes with adhesion. Pericardium regeneration was demonstrated by immunohistochemical technique to identify mesothelial cells. In Group D, the serum concentration of tumor necrosis factor-α (TNF-α) was significantly lower in the early postoperative period, and the mean adhesion score (adhesion between the epicardium and ABP) was significantly lower compared with the control group (Groups D vs. A: 0.20 ± 0.45 vs. 2.00 ± 0.71, P = 0.009*). The signs of degradation of the ABPs were observed 2 months postoperation in Groups D and B. Immunohistochemically, the positive cytokeratin AE1 staining results demonstrated the relatively total regeneration of the pericardium in Group D. Signs of regeneration were observed in Group D. Compared with the control group, the level of TGF-β2 in Group D was significantly lower (0.00132 ± 0.00114, P = 0.022*). The TGF-β3 level was statistically significant, being highest in Group D (0.00805 ± 0.00136, P = 0.029*). The mean quantity of Smad6 in

  9. Calcium and linoleic acid supplements in the prevention of pre-eclampsia.

    Directory of Open Access Journals (Sweden)

    Leonelo E Bautista

    2016-04-01

    Full Text Available Alzate et al.1, conducted a nested case-control study to (quote “estimate the protective effect from calcium [supplement] alone [CC], compared to calcium plus conjugated linoleic acid [CC+CLA] in nulliparous women at risk of preeclampsia”. Based on a crude analysis of the data in Table 3,1 they concluded that neither CC nor CC+CLA reduced the risk of preeclampsia in the whole sample, but that CC+CLA significantly decreased risk among women 13-18 years old. A quick look analysis of the data in this table shows this conclusion is mostly based on the fact that none of the cases in 13-18 year old women was treated with CC+CLA. Contrary to the authors’ interpretation, this does not point to a protective effect of CC+CLA, it simply indicates that the assumption of positivity has being violated and, consequently, that an effect for this age group cannot be estimated2. In fact, the probability of getting no treated cases in this age-group was 28%, since only 15.5% of all women received CC+CLA. Also, accurate estimates of effect in women 34-45 years old were not possible, because there were only seven women who used CC+CLA in this age group. In spite of the limited sample size, the authors restricted their attention to the apparent protective effect of CC+CLA in 13-19 year old women, while ignoring apparent harmful effects in older women. I estimated age-specific rate ratios (RR by fitting a saturated conditional complementary log-log3 to the data in Table 3 and found that CC+CLA was protective among women 13-19 (RR= 0.61, 95% CI: 0.41- 0.90, but harmful in women 19-34 (RR= 1.74, 95% CI: 1.21- 2.50 and 35-45 years old (RR= 4.98, 95% CI= 1.74-14.30. Of course, this approach is an improvement over a naive crude analysis, but does not solve the problem of violation and near violation of positivity described above. An overall age-adjusted RR was 1.02 (95% CI= 0.89-1.17; p= 0.756. Thus, this study provides no evidence of a beneficial effect of CC+CLA in

  10. Acanthoic Acid Can Partially Prevent Alcohol Exposure-Induced Liver Lipid Deposition and Inflammation

    Science.gov (United States)

    Yao, You-Li; Han, Xin; Li, Zhi-Man; Lian, Li-Hua; Nan, Ji-Xing; Wu, Yan-Ling

    2017-01-01

    droplets, and SREBP-1 and CYP2E1 expressions, compared with EtOH/LPS treatment. AA also significantly increased protein expressions of Sirt1, p-LKB1, p-ACC, PPARα, and decreased protein expression of PPARγ, compared with EtOH/LPS treatment. Conclusion: Acanthoic acid can partially prevent alcohol exposure-induced liver lipid deposition and inflammation via regulation of LKB1/Sirt1/AMPK/ACC and LXRs pathways. PMID:28360860

  11. Linolenic acid prevents early and advanced glycation end-products (AGEs) modification of albumin.

    Science.gov (United States)

    Prasanna, Govindarajan; Saraswathi, N T

    2017-02-01

    In this study, we report the protective effects of linolenic acid towards the formation of early (HbA1c) and advanced glycation end-products (AGEs) based on fluorescence, circular dichroism, confocal microscopy and molecular interaction studies. Linolenic acid was found to be a potent inhibitor of AGEs formed by both glucose and fructose. The HbA1c (early glycation product) level was found to be reduced to 7.4% when compared to glycated control (8.4%). Similarly, linolenic acid also inhibited the methylglyoxal mediated AGEs formation. Circular dichroism spectroscopy studies suggested that the protective effect of linolenic acid for the helical structure of albumin. The molecular interaction studies showed that linolenic acid interacts with arginine residues of albumin with high affinity. Results suggested linolenic acid to be a potent antiglycation compound and also it could be a better lead compound for AGE inhibition.

  12. Preventive effect of phytic acid on lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats.

    Science.gov (United States)

    Brindha, E; Rajasekapandiyan, M

    2015-02-01

    This study was aimed to evaluate the preventive role of phytic acid on lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for two days showed a significant increase in the activities of lysosomal enzymes (glucuronidase, N-acetyl glucosaminidase, galactosidase, cathepsin-B and cathepsin-D) were increased significantly in serum and the heart of ISO-induced rats, but the activities of glucuronidase and cathepsin-D were decreased significantly in the lysosomal fraction of the heart. Pretreatment with phytic acid (25 and 50 mg/kg) daily for a period of 56 d positively altered activities of lysosomal hydrolases in ISO-induced rats. Thus, phytic acid possesses a cardioprotective effect in ISO-induced MI in rats.

  13. The rationale for preventing cancer cachexia: targeting excessive fatty acid oxidation

    OpenAIRE

    2016-01-01

    Cachexia commonly occurs at the terminal stage of cancer and has largely unclear molecular mechanisms. A recent study published in Nature Medicine, entitled “Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia,” reveals that cachectic cancer cells can secrete multiple cytokines that induce excessive fatty acid oxidation, which is responsible for muscle loss in cancer cachexia. Inhibition of fatty acid oxidation using etomoxir can increase muscle mass and body weight in ca...

  14. Preventive Effects of Folic Acid Supplementation on Adverse Maternal and Fetal Outcomes

    OpenAIRE

    Min Woo Kim; Ki Hoon Ahn; Ki-Jin Ryu; Soon-Cheol Hong; Ji Sung Lee; Nava-Ocampo, Alejandro A.; Min-Jeong Oh; Hai-Joong Kim

    2014-01-01

    Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplement...

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

    Directory of Open Access Journals (Sweden)

    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. 

  16. "Oral ascorbic acid in combination with beta blockers in prevention of atrial fibrillation after Coronary Artery Bypass Graft "

    Directory of Open Access Journals (Sweden)

    Mousavi M

    2007-04-01

    Full Text Available Background: Adrenergic beta antagonists are not sufficient to prevent atrial fibrillation after coronary artery bypass graft (CABG. This study was designed to evaluate the effect of ascorbic acid as an adjunct to beta-blockers in prevention of post-CABG atrial fibrillation Methods: Patients who were more than 50 years old and scheduled to undergo CABG were included if they were treated with beta-blockers at least 1 week before surgery. Patients with previous history of atrial fibrillation, AV block, heart rate <50 /min, end-stage renal disease, severe pulmonary or liver disease and those who were taking digoxin or class I and III anti-arrhythmics or had pacemakers were not included. Ascorbic acid group were prescribed 2 gm of ascorbic acid, the night before the surgery, and 1 gm twice daily for 5 days after surgery. Beta blockers continued in both group after surgery. Telemetry monitoring was performed in ICU and Holter monitoring was performed for 4 days. Results: Fifty patients completed the study as ascorbic acid and 50 as control group. The population was 60.19 ± 7.14 years old and 67% were male. The incidence of postoperative atrial fibrillation was 4% in the ascorbic acid group and 26% in control group (odds ratio=0.119, 95% confidence interval: 0.025 to 0.558, P=0.002 Conclusion: Ascorbic acid is well-tolerated, relatively safe and seems effective. Therefore it can be prescribed as an adjunct to beta-blockers for prophylaxis of post-CABG atrial fibrillation.

  17. Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification.

    Science.gov (United States)

    Gray, Nora E; Zweig, Jonathan A; Murchison, Charles; Caruso, Maya; Matthews, Donald G; Kawamoto, Colleen; Harris, Christopher J; Quinn, Joseph F; Soumyanath, Amala

    2017-04-12

    The medicinal plant Centella asiatica has long been used to improve memory and cognitive function. We have previously shown that a water extract from the plant (CAW) is neuroprotective against the deleterious cognitive effects of amyloid-β (Aβ) exposure in a mouse model of Alzheimer's disease, and improves learning and memory in healthy aged mice as well. This study explores the physiological underpinnings of those effects by examining how CAW, as well as chemical compounds found within the extract, modulate synaptic health in Aβ-exposed neurons. Hippocampal neurons from amyloid precursor protein over-expressing Tg2576 mice and their wild-type (WT) littermates were used to investigate the effect of CAW and various compounds found within the extract on Aβ-induced dendritic simplification and synaptic loss. CAW enhanced arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites and loss of spines caused by Aβ exposure in Tg2576 neurons. Triterpene compounds present in CAW were found to similarly improve arborization although they did not affect spine density. In contrast caffeoylquinic acid (CQA) compounds from CAW were able to modulate both of these endpoints, although there was specificity as to which CQAs mediated which effect. These data suggest that CAW, and several of the compounds found therein, can improve dendritic arborization and synaptic differentiation in the context of Aβ exposure which may underlie the cognitive improvement observed in response to the extract in vivo. Additionally, since CAW, and its constituent compounds, also improved these endpoints in WT neurons, these results may point to a broader therapeutic utility of the extract beyond Alzheimer's disease.

  18. Iron prevents ascorbic acid (vitamin C) induced hydrogen peroxide accumulation in copper contaminated drinking water.

    Science.gov (United States)

    Jansson, Patric J; Lindqvist, Christer; Nordström, Tommy

    2005-11-01

    Ascorbic acid (vitamin C) induced hydrogen peroxide (H(2)O(2)) formation was measured in household drinking water and metal supplemented Milli-Q water by using the FOX assay. Here we show that ascorbic acid readily induces H(2)O(2) formation in Cu(II) supplemented Milli-Q water and poorly buffered household drinking water. In contrast to Cu(II), iron was not capable to support ascorbic acid induced H(2)O(2) formation during acidic conditions (pH: 3.5-5). In 12 out of the 48 drinking water samples incubated with 2 mM ascorbic acid, the H(2)O(2) concentration exceeded 400 microM. However, when trace amounts of Fe(III) (0.2 mg/l) was present during incubation, the ascorbic acid/Cu(II)-induced H(2)O(2) accumulation was totally blocked. Of the other common divalent or trivalent metal ions tested, that are normally present in drinking water (calcium, magnesium, zinc, cobalt, manganese or aluminum), only calcium and magnesium displayed a modest inhibitory activity on the ascorbic acid/Cu(II)-induced H(2)O(2) formation. Oxalic acid, one of the degradation products from ascorbic acid, was confirmed to actively participate in the iron induced degradation of H(2)O(2). Ascorbic acid/Cu(II)-induced H(2)O(2) formation during acidic conditions, as demonstrated here in poorly buffered drinking water, could be of importance in host defense against bacterial infections. In addition, our findings might explain the mechanism for the protective effect of iron against vitamin C induced cell toxicity.

  19. Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic acid: a Potential Role in Cancer Prevention

    Science.gov (United States)

    Dachineni, Rakesh; Ai, Guoqiang; Kumar, D. Ramesh; Sadhu, Satya S.; Tummala, Hemachand; Bhat, G. Jayarama

    2015-01-01

    Data emerging from the past 10 years have consolidated the rationale for investigating the use of aspirin as a chemopreventive agent; however, the mechanisms leading to its anti-cancer effects are still being elucidated. We hypothesized that aspirin’s chemopreventive actions may involve cell cycle regulation through modulation of the levels or activity of cyclin A2/cyclin dependent kinase-2 (CDK2). In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. The down regulatory effect of either drugs on cyclin A2 levels was prevented by pretreatment with lactacystin, an inhibitor of proteasomes, suggesting the involvement of 26S proteasomes. In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. Firstly, inclusion of salicylic acid in naïve cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Secondly, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, pre-incubation of CDK2 with salicylic acid, dose-dependently quenched the fluorescence due to ANS. Thirdly, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. These results demonstrate that aspirin and salicylic acid down-regulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. Implications Biochemical and structural studies indicate that the anti-proliferative actions of aspirin are mediated through cyclin A2/CDK2. PMID:26685215

  20. Targeting arachidonic acid pathway to prevent programmed hypertension in maternal fructose-fed male adult rat offspring.

    Science.gov (United States)

    Tain, You-Lin; Lee, Wei-Chia; Wu, Kay L H; Leu, Steve; Chan, Julie Y H

    2016-12-01

    Hypertension can be programmed in response to nutritional insults in early life. Maternal high-fructose (HF) intake induced programmed hypertension in adult male offspring, which is associated with renal programming and arachidonic acid metabolism pathway. We examined whether early treatment with a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-Deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) can prevent HF-induced programmed hypertension. Pregnant Sprague Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) during the whole period of pregnancy and lactation. Four groups of male offspring were studied: control, HF, HF+AUDA and HF+15dPGJ2. In HF+AUDA group, mother rats received AUDA 25 mg/L in drinking water during lactation. In the HF+15dPGJ2 group, male offspring received 15dPGJ2 1.5 mg/kg body weight by subcutaneous injection once daily for 1 week after birth. Rats were sacrificed at 12 weeks of age. Maternal HF-induced programmed hypertension is associated with increased renal protein level of SEH and oxidative stress, which early AUDA therapy prevents. Comparison of AUDA and 15dPGJ2 treatments demonstrated that AUDA was more effective in preventing HF-induced programmed hypertension. AUDA therapy increases angiotensin converting enzyme-2 (ACE2) protein levels and PGE2 levels in adult offspring kidney exposed to maternal HF. 15dPGJ2 therapy increases plasma asymmetric dimethylarginine (ADMA) levels and decreases L-arginine-to-ADMA ratio. Better understanding of the impact of arachidonic acid pathway, especially inhibition of SEH, on renal programming may aid in developing reprogramming strategy to prevent programmed hypertension in children exposed to antenatal HF intake.

  1. Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats.

    Science.gov (United States)

    Yüce, Abdurrauf; Ateşşahin, Ahmet; Ceribaşi, Ali Osman; Aksakal, Mesut

    2007-11-01

    Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity, and several studies suggest that supplemental antioxidants can reduce cisplatin-induced hepatotoxicity. The present study was designed to determine the effects on the liver and heart oxidant/antioxidant system and the possible protective effects of ellagic acid on liver and heart toxicity induced by cisplatin. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The rats were killed at the end of the treatment period. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione-peroxidase (GSH-Px) and catalase (CAT) activities were determined in liver and heart tissue. While administration of cisplatin increased the MDA levels in liver and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when compared to the control group. The administration of ellagic acid to cisplatin-treated rats decreased the MDA levels, and increased GSH, GSH-Px and CAT in these samples. Cisplatin caused marked damages in the histopathological status of liver and heart tissues. These damages were ameliorated by ellagic acid administration. In conclusion, ellagic acid may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters.

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

    Science.gov (United States)

    Jin, Song [Fort Collins, CO; Fallgren, Paul H [Laramie, WY; Morris, Jeffrey M [Laramie, WY

    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.

  3. Preventive effect of α-lipoic acid on prepulse inhibition deficits in a juvenile two-hit model of schizophrenia.

    Science.gov (United States)

    Deslauriers, J; Racine, W; Sarret, P; Grignon, S

    2014-07-11

    Some pathophysiological models of schizophrenia posit that prenatal inflammation sensitizes the developing brain to second insults in early life and enhances brain vulnerability, thereby increasing the risk of developing the disorder during adulthood. We previously developed a two-hit animal model, based on the well-established prenatal immune challenge with poly-inosinic/cytidylic acid (polyI:C), followed by juvenile restraint stress (RS). We observed an additive disruption of prepulse inhibition (PPI) of acoustic startle in juvenile mice submitted to both insults. Previous studies have also reported that oxidative stress is associated with pathophysiological mechanisms of psychiatric disorders, including schizophrenia. We report here that PPI disruption in our two-hit animal model of schizophrenia is associated with an increase in oxidative stress. These findings led us to assess whether α-lipoic acid, an antioxidant, can prevent both increase in oxidative status and PPI deficits in our juvenile in vivo model of schizophrenia. In the offspring submitted to prenatal injection of polyI:C and to RS, treatment with α-lipoic acid prevented the development of PPI deficits 24h after the last period of RS. α-Lipoic acid also improved PPI performance in control mice. The reversal effect of α-lipoic acid pretreatment on these behavioral alterations was further accompanied by a normalization of the associated oxidative status and dopaminergic and GABAergic abnormalities in the prefrontal cortex. Based on our double insult paradigm, these results support the hypothesis that oxidative stress plays an important role in the development of PPI deficits, a well-known behavior associated with schizophrenia. These findings form the basis of future studies aiming to unravel mechanistic insights of the putative role of antioxidants in the treatment of schizophrenia, especially during the prodromal stage.

  4. Clomipramine causes osteoporosis by promoting osteoclastogenesis via E3 ligase Itch, which is prevented by Zoledronic acid

    Science.gov (United States)

    Li, Xing; Sun, Wen; Li, Jinbo; Wang, Mengmeng; Zhang, Hengwei; Pei, Lingpeng; Boyce, Brendan F.; Wang, Zhiyu; Xing, Lianping

    2017-01-01

    Patients taking antidepressants, including Clomipramine (CLP), have an increased risk of osteoporotic fracture. However, the effects of CLP on bone metabolism are unknown. Here, we demonstrate that WT mice treated with CLP for 2 weeks had significantly reduced trabecular bone volume and cortical bone thickness, associated with increased osteoclast (OC) numbers, but had no change in osteoblast numbers or bone formation rate. Bone marrow cells from CLP-treated mice had normal OC precursor frequency, but formed significantly more OCs when they were cultured with RANKL and M-CSF. CLP promoted OC formation and bone resorption and expression of OC-associated genes. CLP-induced bone loss was prevented by Zoledronic acid. At the molecular level, CLP inhibited the activity of the ubiquitin E3 ligase Itch. CLP did not promote OC formation from bone marrow cells of Itch−/− mice in vitro nor induce bone loss in Itch−/− mice. Our findings indicate that CLP causes bone loss by enhancing Itch-mediated osteoclastogenesis, which was prevented by Zoledronic acid. Thus, anti-resorptive therapy could be used to prevent bone loss in patients taking antidepressants, such as CLP. PMID:28145497

  5. Coding and decoding with dendrites.

    Science.gov (United States)

    Papoutsi, Athanasia; Kastellakis, George; Psarrou, Maria; Anastasakis, Stelios; Poirazi, Panayiota

    2014-02-01

    Since the discovery of complex, voltage dependent mechanisms in the dendrites of multiple neuron types, great effort has been devoted in search of a direct link between dendritic properties and specific neuronal functions. Over the last few years, new experimental techniques have allowed the visualization and probing of dendritic anatomy, plasticity and integrative schemes with unprecedented detail. This vast amount of information has caused a paradigm shift in the study of memory, one of the most important pursuits in Neuroscience, and calls for the development of novel theories and models that will unify the available data according to some basic principles. Traditional models of memory considered neural cells as the fundamental processing units in the brain. Recent studies however are proposing new theories in which memory is not only formed by modifying the synaptic connections between neurons, but also by modifications of intrinsic and anatomical dendritic properties as well as fine tuning of the wiring diagram. In this review paper we present previous studies along with recent findings from our group that support a key role of dendrites in information processing, including the encoding and decoding of new memories, both at the single cell and the network level. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. The rationale for preventing cancer cachexia: targeting excessive fatty acid oxidation.

    Science.gov (United States)

    Qian, Chao-Nan

    2016-07-21

    Cachexia commonly occurs at the terminal stage of cancer and has largely unclear molecular mechanisms. A recent study published in Nature Medicine, entitled "Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia," reveals that cachectic cancer cells can secrete multiple cytokines that induce excessive fatty acid oxidation, which is responsible for muscle loss in cancer cachexia. Inhibition of fatty acid oxidation using etomoxir can increase muscle mass and body weight in cancer cachexia animal models. The usage of stable cachexia animal models is also discussed in this research highlight.

  7. Dendritic Cells—Ontogeny—

    Directory of Open Access Journals (Sweden)

    Satoshi Takeuchi

    2007-01-01

    Full Text Available Dendritic cells (DC play key rolls in various aspects of immunity. The functions of DC depend on the subsets as well as their location or activation status. Understanding developmental lineages, precursors and inducing factors for various DC subsets would help their clinical application, but despite extensive efforts, the precise ontogeny of various DC, remain unclear and complex. Because of their many functional similarities to macrophages, DC were originally thought to be of myeloid-lineage, an idea supported by many in vitro studies where monocytes or GM-CSF (a key myeloid growth factor has been extensively used for generating DC. However, there has been considerable evidence which suggests the existence of lymphoid-lineage DC. After the confusion of myeloid-/lymphoid-DC concept regarding DC surface markers, we have now reached a consensus that each DC subset can differentiate through both myeloid- and lymphoid-lineages. The identification of committed populations (such as common myeloid- and lymphoid progenitors as precursors for every DC subsets and findings from various knockout (KO mice that have selected lymphoid- or myeloid-lineage deficiency appear to indicate flexibility of DC development rather than their lineage restriction. Why is DC development so flexible unlike other hematopoitic cells? It might be because there is developmental redundancy to maintain such important populations in any occasions, or such developmental flexibility would be advantageous for DC to be able to differentiate from any “available” precursors in situ irrespective of their lineages. This review will cover ontogeny of conventional (CD8+/- DC DC, plasmacytoid DC and skin Langerhans cells, and recently-identified many Pre-DC (immediate DC precursor populations, in addition to monocytes and plasmacytoid DC, will also be discussed.

  8. Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    J. Thomas

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is the leading cause of dementia and the most common neurodegenerative disease in the elderly. Furthermore, AD has provided the most positive indication to support the fact that inflammation contributes to neurodegenerative disease. The exact etiology of AD is unknown, but environmental and genetic factors are thought to contribute, such as advancing age, family history, presence of chronic diseases such as cardiovascular disease (CVD and diabetes, and poor diet and lifestyle. It is hypothesised that early prevention or management of inflammation could delay the onset or reduce the symptoms of AD. Normal physiological changes to the brain with ageing include depletion of long chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic acid (DHA levels. DHA supplementation can reduce markers of inflammation. This review specifically focusses on the evidence in humans from epidemiological, dietary intervention, and supplementation studies, which supports the role of long chain omega-3 fatty acids in the prevention or delay of cognitive decline in AD in its early stages. Longer term trials with long chain omega-3 supplementation in early stage AD are warranted. We also highlight the importance of overall quality and composition of the diet to protect against AD and dementia.

  9. Prevention of bovine mastitis by a postmilking teat disinfectant containing chlorous acid and chlorine dioxide in a soluble polymer gel.

    Science.gov (United States)

    Oliver, S P; King, S H; Torre, P M; Shull, E P; Dowlen, H H; Lewis, M J; Sordillo, L M

    1989-11-01

    A natural exposure study was conducted in a herd of 150 lactating dairy cows for 18 mo to determine the effectiveness of chlorous acid and chlorine dioxide in a soluble polymer gel as a postmilking teat disinfectant for the prevention of bovine mastitis. Right quarters of cows were dipped in the experimental teat dip after milking machine removal. Left quarters were not dipped and served as within-cow negative controls. The experimental teat dip reduced Staphylococcus aureus infections 67.4%, Streptococcus dysgalactiae infections 63.8%, and Streptococcus uberis infections 27.8%. Overall efficacy of the chlorous acid and chlorine dioxide teat dip against major mastitis pathogens was 52.2%. The experimental teat dip reduced Corynebacterium bovis infections and coagulase-negative staphylococcal infections also by 45.8 and 38.7%, respectively. Overall efficacy against minor mastitis pathogens was 43.4%. Under conditions of this trial, the experimental teat dip containing chlorous acid and chlorine dioxide was effective in preventing new intramammary infections against a variety of mastitis pathogens.

  10. Knowledge and use of folic acid for prevention of birth defects amongst Honduran women.

    Science.gov (United States)

    Wu, D Ying; Brat, Gabriel; Milla, Gayle; Kim, Jae

    2007-06-01

    To characterize determinants of folic acid (FA) use among women of reproductive age and patient education practices of health care professionals in one region of Honduras. 508 female outpatients and 128 health workers were interviewed in six primary care clinics in Honduras. Results were analyzed using univariate and multivariate regression models. The survey showed that 45% patients were familiar with FA. Of that number, 30% knew appropriate timing of consumption and 25% reported proper pre-natal supplementation. Increasing education was strongly correlated with knowledge of folic acid function (OR=252.52, Pknowledge of proper timing of FA usage (OR=3.94, Pfolic acid with their patients, particularly those of low education and at the extremes of reproductive age. While long-term efforts to develop fortification programs continue, interim Honduran health campaigns to increase proper consumption of folic acid should target these particularly vulnerable populations.

  11. [A two-faced vitamin : Folic acid - prevention or promotion of colon cancer?

    Science.gov (United States)

    Weißenborn, Anke; Ehlers, Anke; Hirsch-Ernst, Karen-I; Lampen, Alfonso; Niemann, Birgit

    2017-03-01

    In the late 1930s, it was discovered that liver and yeast extracts can be used to correct certain cases of megaloblastic anemia in pregnancy. The factor responsible for this was isolated from spinach leaves in the 1940s, and referred to as folate, a term derived from the Latin word folium for leaf. Folate is considered an essential nutrient for human beings. Folic acid, the synthetic form of the vitamin, is used in dietary supplements, medicines and fortified foods. Since the 1980s, it has been recommended that women who plan to become pregnant and pregnant women during the first trimester of pregnancy take folic acid supplements. This recommendation was based on studies that revealed that periconceptional folic acid supplementation can reduce the risk for neural tube defects (NTDs). Many countries later implemented folic acid fortification programs. The resulting population-wide increase of folic acid intakes led to significant reductions in NTD rates. However, a temporarily increased colorectal cancer incidence has been reported to coincide with the fortification programs in the USA and Canada. On the basis of currently available data from experimental and human studies it can be concluded that the association between folate/folic acid and cancer is rather complex: Folate intake in the range of the dietary reference intake (DRI) is associated with a reduced risk for cancer in healthy populations, whereas high intakes of folic acid might result in an increased risk for cancer incidence or progression in persons with precancerous lesions and under certain conditions. Since no adverse effects have been observed in association with the intake of dietary folate, research activities that aim at investigating cause and effect relationships focus on folic acid.

  12. Natural xenobiotics to prevent cyanobacterial and algal growth in freshwater: contrasting efficacy of tannic acid, gallic acid, and gramine.

    Science.gov (United States)

    Laue, Pauline; Bährs, Hanno; Chakrabarti, Shumon; Steinberg, Christian E W

    2014-06-01

    Allelochemical action against planktonic phototrophs is one central issue in freshwater ecology and quality management. To determine some basic mechanisms of this toxic action, we exposed the coccal green alga, Desmodesmus armatus, and the coccal cyanobacterium, Microcystis aeruginosa, in a batch culture well-supplied with carbon dioxide to increasing concentrations of the polyphenols tannic acid and gallic acid and the alkaloid gramine. The phototrophs were checked after 2d and at the end of the culture for biomass-based growth rates, cell volume, maximum quantum yield of photosystem II (ΦPSIImax), chlorophyll a content (chla) after 2d and at the end of the culture, and lipid peroxidation only at the end of the culture. During the culture, the pH rose from 7.64 to 10.95, a pH characteristic of eutrophic freshwater bodies during nuisance algal blooms. All xenobiotics reduced the growth rate, ΦPSIImax, and chla during the first 2d with M. aeruginosa being more sensitive to the polyphenols than D. armatus. The efficacy of the polyphenols declined with increasing pH, indicating potential polymerization and corresponding reduced bioavailability of the polyphenols. In contrast to the polyphenols, gramine increased its toxic action over time, independent of the prevailing pH. All exposures caused slight to severe lipid peroxidation (LPO) in the phototrophs. Hence, one mechanism of growth inhibition may be oxidative stress-mediated reduction in photosynthesis. The presented results suggest that in successful field trials with leachate, the prevailing environmental conditions may inactivate polyphenols and xenobiotics other than polyphenols may be more effective.

  13. Potential mechanisms explaining why hydrolyzed casein-based diets outclass single amino acid-based diets in the prevention of autoimmune diabetes in diabetes-prone BB rats

    NARCIS (Netherlands)

    Visser, J. T. J.; Bos, N. A.; Harthoorn, L. F.; Stellaard, F.; Beijer-Liefers, S.; Rozing, J.; van Tol, E. A. F.

    Background It remains controversial whether avoidance of dietary diabetogenic triggers, such as cow's milk proteins, can prevent type 1 diabetes in genetically susceptible individuals. Here, different extensive casein hydrolysates (HC) and single amino acid (AA) formulations were tested for their

  14. Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice

    Science.gov (United States)

    Park, Han-Sol; Jang, Jung Eun; Ko, Myoung Seok; Woo, Sung Hoon; Kim, Bum Joong; Kim, Hyun Sik; Park, Hye Sun; Park, In-Sun; Koh, Eun Hee

    2016-01-01

    Background Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown. Methods Seven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD) with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day), for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver. Results Statin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα) were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels. Conclusion Statins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH.

  15. The Deterministic Dendritic Cell Algorithm

    CERN Document Server

    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.

  16. Fabrication of 2D and 3D dendritic nanoarchitectures of CdS

    Institute of Scientific and Technical Information of China (English)

    GU Li

    2008-01-01

    The controlled preparation of two-dimensional (2D) and three-dimensional (3D) dendritic nanostructures of CdS was reported. 2D dendritic patterns are obtained through the self-assembly of nanoparticles under the entropy-driven force. 3D dendritic needle-like nanocrystals are prepared through an aqueous solution synthesis regulated by oleic acid molecules. Their growth mechanism is presumed to be the selective binding of OA molecules onto growing crystal planes. Techniques such as SEM, TEM, XRD, and FT-IR were employed to characterize the morphologies and structures of the obtained products.

  17. Melatonin prevents myeloperoxidase heme destruction and the generation of free iron mediated by self-generated hypochlorous acid.

    Directory of Open Access Journals (Sweden)

    Faten Shaeib

    Full Text Available Myeloperoxidase (MPO generated hypochlorous acid (HOCl formed during catalysis is able to destroy the MPO heme moiety through a feedback mechanism, resulting in the accumulation of free iron. Here we show that the presence of melatonin (MLT can prevent HOCl-mediated MPO heme destruction using a combination of UV-visible photometry, hydrogen peroxide (H2O2-specific electrode, and ferrozine assay techniques. High performance liquid chromatography (HPLC analysis showed that MPO heme protection was at the expense of MLT oxidation. The full protection of the MPO heme requires the presence of a 1:2 MLT to H2O2 ratio. Melatonin prevents HOCl-mediated MPO heme destruction through multiple pathways. These include competition with chloride, the natural co-substrate; switching the MPO activity from a two electron oxidation to a one electron pathway causing the buildup of the inactive Compound II, and its subsequent decay to MPO-Fe(III instead of generating HOCl; binding to MPO above the heme iron, thereby preventing the access of H2O2 to the catalytic site of the enzyme; and direct scavenging of HOCl. Collectively, in addition to acting as an antioxidant and MPO inhibitor, MLT can exert its protective effect by preventing the release of free iron mediated by self-generated HOCl. Our work may establish a direct mechanistic link by which MLT exerts its antioxidant protective effect in chronic inflammatory diseases with MPO elevation.

  18. Effect of beta-muricholic acid on the prevention and dissolution of cholesterol gallstones in C57L/J mice.

    Science.gov (United States)

    Wang, David Q-H; Tazuma, Susumu

    2002-11-01

    This study investigated whether beta-muricholic acid, a natural trihydroxy hydrophilic bile acid of rodents, acts as a biliary cholesterol-desaturating agent to prevent cholesterol gallstones and if it facilitates the dissolution of gallstones compared with ursodeoxycholic acid (UDCA). For gallstone prevention study, gallstone-susceptible male C57L mice were fed 8 weeks with a lithogenic diet (2% cholesterol and 0.5% cholic acid) with or without 0.5% UDCA or beta-muricholic acid. For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% beta-muricholic acid or UDCA for 8 weeks. One hundred percent of mice fed the lithogenic diet formed cholesterol gallstones. Addition of beta-muricholic acid and UDCA decreased gallstone prevalence to 20% and 50% through significantly reducing biliary secretion rate, saturation index, and intestinal absorption of cholesterol, as well as inducing phase boundary shift and an enlarged Region E that prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones. Eight weeks of beta-muricholic acid and UDCA administration produced complete gallstone dissolution rates of 100% and 60% compared with the chow (10%). We conclude that beta-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Dendritic cells star in Vancouver

    OpenAIRE

    Klechevsky, Eynav; Kato, Hiroki; Sponaas, Anne-Marit

    2005-01-01

    The fast-moving field of dendritic cell (DC) biology is hard to keep pace with. Here we report on advances from the recent Keystone Symposium, “Dendritic Cells at the Center of Innate and Adaptive Immunity,” organized in Vancouver, BC on Feb. 1–7, 2005 by Anne O'Garra, Jacques Banchereau, and Alan Sher. New insights into the molecular mechanisms of DC function and their influence on immune regulation, their role in infectious and autoimmune disease, and new clinical applications are highlight...

  1. Cellular source-specific effects of apolipoprotein (apo) E4 on dendrite arborization and dendritic spine development.

    Science.gov (United States)

    Jain, Sachi; Yoon, Seo Yeon; Leung, Laura; Knoferle, Johanna; Huang, Yadong

    2013-01-01

    Apolipoprotein (apo) E4 is the leading genetic risk factor for Alzheimer's disease (AD), and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4's cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin (learning) and mushroom (memory) spines, in the hippocampus and entorhinal cortex of 19-21-month-old female neuron-specific-enolase (NSE)-apoE4 and apoE4-knockin (KI) mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7-8 months of age. In contrast, glial fibrillary acidic protein (GFAP)-apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4.

  2. Cellular source-specific effects of apolipoprotein (apo E4 on dendrite arborization and dendritic spine development.

    Directory of Open Access Journals (Sweden)

    Sachi Jain

    Full Text Available Apolipoprotein (apo E4 is the leading genetic risk factor for Alzheimer's disease (AD, and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4's cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin (learning and mushroom (memory spines, in the hippocampus and entorhinal cortex of 19-21-month-old female neuron-specific-enolase (NSE-apoE4 and apoE4-knockin (KI mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7-8 months of age. In contrast, glial fibrillary acidic protein (GFAP-apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4.

  3. Once-yearly zoledronic acid in the prevention of osteoporotic bone fractures in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Irene Lambrinoudaki

    2008-09-01

    Full Text Available Irene Lambrinoudaki, Sophia Vlachou, Fotini Galapi, Dimitra Papadimitriou, K Papadias2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, GreeceAbstract: Zoledronic acid is a nitrogen-containing, third-generation bisphosphonate that has recently been approved for the treatment of postmenopausal osteoporosis as an annual intravenous infusion. Zoledronic acid is an antiresorptive agent which has a high affinity for mineralized bone and especially for sites of high bone turnover. Zoledronic acid is excreted by the kidney without further metabolism. Zoledronic acid administered as a 5 mg intravenous infusion annually increases bone mineral density in the lumbar spine and femoral neck by 6.7% and 5.1% respectively and reduces the incidence of new vertebral and hip fractures by 70% and 41% respectively in postmenopausal women with osteoporosis. Most common side effects are post-dose fever, flu-like symptoms, myalgia, arthralgia, and headache which usually occur in the first 3 days after infusion and are self-limited. Rare adverse effects include renal dysfunction, hypocalcemia, atrial fibrillation, and osteonecrosis of the jaw.Keywords: zoledronic acid, postmenopausal osteoporosis, bisphosphonate

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. [Management, prevention and control of megaloblastic anemia, secondary to folic acid deficiency].

    Science.gov (United States)

    de Paz, R; Hernández-Navarro, F

    2006-01-01

    Folic acid deficiency is the second most common cause of anemia in our environment, after anemia secondary to iron deficiency. Folates are essential components of human and animal diet. Folic acid is mainly in poliglutamate form, and it is hydrolyzed in the proximal jejunum. It is important to identify adequately the exact vitamin deficiency that causes megaloblastic anemia, because vitamin B12 administration in folate deficiency may correct partially megaloblastic alterations, but administration of folic acid in cobalamin deficient patients improves haematological parameters but deteriorates the neurological syndrome. Main causes of anemia secondary to folate deficiency are inadequate dietetic administration, increased requirements, impaired absorption and pharmacologic interactions. Folates are altered by light, high temperature and by water affinity, which facilitates its elimination by washing or cooking.

  6. Prevention of Diet-Induced Metabolic Dysregulation, Inflammation, and Atherosclerosis in Ldlr(-/-) Mice by Treatment With the ATP-Citrate Lyase Inhibitor Bempedoic Acid.

    Science.gov (United States)

    Samsoondar, Joshua P; Burke, Amy C; Sutherland, Brian G; Telford, Dawn E; Sawyez, Cynthia G; Edwards, Jane Y; Pinkosky, Stephen L; Newton, Roger S; Huff, Murray W

    2017-04-01

    Bempedoic acid (ETC-1002, 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel low-density lipoprotein cholesterol-lowering compound. In animals, bempedoic acid targets the liver where it inhibits cholesterol and fatty acid synthesis through inhibition of ATP-citrate lyase and through activation of AMP-activated protein kinase. In this study, we tested the hypothesis that bempedoic acid would prevent diet-induced metabolic dysregulation, inflammation, and atherosclerosis. APPROACH AND RESULTS: Ldlr(-/-) mice were fed a high-fat, high-cholesterol diet (42% kcal fat, 0.2% cholesterol) supplemented with bempedoic acid at 0, 3, 10 and 30 mg/kg body weight/day. Treatment for 12 weeks dose-dependently attenuated diet-induced hypercholesterolemia, hypertriglyceridemia, hyperglycemia, hyperinsulinemia, fatty liver and obesity. Compared to high-fat, high-cholesterol alone, the addition of bempedoic acid decreased plasma triglyceride (up to 64%) and cholesterol (up to 50%) concentrations, and improved glucose tolerance. Adiposity was significantly reduced with treatment. In liver, bempedoic acid prevented cholesterol and triglyceride accumulation, which was associated with increased fatty acid oxidation and reduced fatty acid synthesis. Hepatic gene expression analysis revealed that treatment significantly increased expression of genes involved in fatty acid oxidation while suppressing inflammatory gene expression. In full-length aorta, bempedoic acid markedly suppressed cholesteryl ester accumulation, attenuated the expression of proinflammatory M1 genes and attenuated the iNos/Arg1 ratio. Treatment robustly attenuated atherosclerotic lesion development in the aortic sinus by 44%, with beneficial changes in morphology, characteristic of earlier-stage lesions. Bempedoic acid effectively prevents plasma and tissue lipid elevations and attenuates the onset of inflammation, leading to the prevention of atherosclerotic lesion development in a mouse model of metabolic

  7. Folic acid and the prevention of neural tube defects: A survey of awareness among Latina women of childbearing age residing in southeast Michigan.

    Science.gov (United States)

    Kannan, Srimathi; Menotti, Elaine; Scherer, Holly K; Dickinson, Jennifer; Larson, Kimberly

    2007-01-01

    Periconceptional intake of folic acid is known to reduce the risk for neural tube defects (NTDs). To inform southeast Michigan Latina women of childbearing age about the benefits of food and supplemental sources of the micronutrient in the prevention of NTDs, Spanish-English bilingual health educators carried out 20 education events in supermarkets and community organizations serving Latina women. One hundred and sixty Latina women ages 19 to 50 years indicated their current folic acid awareness and stated their future intentions regarding folic acid. Of 160 women surveyed, 114 (71%) had heard of folic acid, 84 (74%) knew that folic acid prevents birth defects, 63 (55%) knew the critical time to take folic acid, and 76 (67%) identified at least one source of folic acid. After participating in the education events, 136 women (85%) reported planning to eat more folate and/or folic acid-rich foods. Although general folic acid awareness is fairly high, health promotion efforts must be coordinated at community locations serving Latina women to share folic acid's specific protective effects in the prevention of NTDs, the critical timing of intake, and its food and supplement sources.

  8. The combination of acetylsalicylic acid and dipyridamole is more effective in secondary prevention following transient ischaemic attack or cerebral infarction: The debate is closed

    NARCIS (Netherlands)

    Luijckx, G.J.; De Keyser, J.H.A.

    2006-01-01

    The European/Australasian stroke prevention in reversible ischaemia trial (ESPRIT) confirms that long-term administration of the combination acetylsalicylic acid and dipyridamole is more effective than acetylsalicylic acid in reducing the risk of vascular events after cerebral ischaemia of arterial

  9. Cyclic GMP signaling in cardiomyocytes modulates fatty acid trafficking and prevents triglyceride accumulation

    Science.gov (United States)

    While the balance between carbohydrates and fatty acids for energy production appears to be crucial for cardiac homeostasis, much remains to be learned about the molecular mechanisms underlying this relationship. Given the reported benefits of cGMP signaling on the myocardium, we investigated the im...

  10. Combination of Antiestrogens and Omega-3 Fatty Acids for Breast Cancer Prevention.

    Science.gov (United States)

    Manni, Andrea; El-Bayoumy, Karam; Skibinski, Christine G; Thompson, Henry J; Santucci-Pereira, Julia; Bidinotto, Lucas Tadeu; Russo, Jose

    2015-01-01

    The molecular and biological heterogeneity of human breast cancer emphasizes the importance of a multitargeted approach for effective chemoprevention. Targeting the estrogen receptor pathway alone with the antiestrogens, Tamoxifen and Raloxifene reduces the incidence of estrogen receptor positive tumors but is ineffective against the development of hormone independent cancers. Our preclinical data indicate that the administration of omega-3 fatty acids potentiates the antitumor effects of Tamoxifen by inhibiting multiple proliferative and antiapoptotic pathways, several of which interact with estrogen receptor signaling. The complementarity in the mechanism of antitumor action of Tamoxifen and omega-3 fatty acids is well supported by our signaling, genomic, and proteomic studies. Furthermore, administration of omega-3 fatty acids allows the use of lower and, hence, likely less toxic doses of Tamoxifen. If these findings are supported in the clinical setting, the combination of omega-3 fatty acids and anteistrogens may emerge as a promising, effective, and safe chemopreventive strategy to be tested in a large multi-institutional trial using breast cancer incidence as the primary endpoint.

  11. Ascorbic acid prevents cimetidine-induced decrease of serum hydrocortisone concentrations

    NARCIS (Netherlands)

    M.P. Boidin (Marinus Pieter); A. Stuurman (Arie); W. Erdmann (Wilhelm)

    1990-01-01

    markdownabstractAbstract A blind, parallel, prospective, clinical study was conducted to investigate the effect of ascorbic acid on human serum hydrocortisone concentrations which were decreased by the administration of cimetidine. The study population included 16 male adults scheduled for major a

  12. Feast or famine: role of TRPML in preventing cellular amino acid starvation.

    Science.gov (United States)

    Venkatachalam, Kartik; Wong, Ching-On; Montell, Craig

    2013-01-01

    Lysosomal storage diseases are metabolic disorders characterized by the accumulation of acidic vacuoles, and are usually the consequence of the deficiency of an enzyme responsible for the metabolism of vesicular lipids, proteins or carbohydrates. In contrast, mucolipidosis type IV (MLIV), results from the absence of a vesicular Ca ( 2+) release channel called mucolipin 1/transient receptor potential mucolipin 1 (MCOLN1/TRPML1) which is required for the fusion of amphisomes with lysosomes. In Drosophila, ablation of the MCOLN1 homolog (trpml) leads to diminished viability during pupation when the animals rely on autophagy for nutrients. This pupal lethality results from decreased target of rapamycin complex 1 (TORC1) signaling, and is reversed by reactivating TORC1. Our findings indicate that one of the primary causes of toxicity in the absence of TRPML is cellular amino acid starvation, and the resulting decrease in TORC1 activity. Furthermore, our findings raise the intriguing possibility that the neurological dysfunction in MLIV patients may arise from amino acid deprivation in neurons. Therefore, future studies evaluating the levels of amino acids and TORC1 activity in MLIV neurons may aid in the development of novel therapeutic strategies to combat the severe manifestations of MLIV.

  13. Combination of Antiestrogens and Omega-3 Fatty Acids for Breast Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Andrea Manni

    2015-01-01

    Full Text Available The molecular and biological heterogeneity of human breast cancer emphasizes the importance of a multitargeted approach for effective chemoprevention. Targeting the estrogen receptor pathway alone with the antiestrogens, Tamoxifen and Raloxifene reduces the incidence of estrogen receptor positive tumors but is ineffective against the development of hormone independent cancers. Our preclinical data indicate that the administration of omega-3 fatty acids potentiates the antitumor effects of Tamoxifen by inhibiting multiple proliferative and antiapoptotic pathways, several of which interact with estrogen receptor signaling. The complementarity in the mechanism of antitumor action of Tamoxifen and omega-3 fatty acids is well supported by our signaling, genomic, and proteomic studies. Furthermore, administration of omega-3 fatty acids allows the use of lower and, hence, likely less toxic doses of Tamoxifen. If these findings are supported in the clinical setting, the combination of omega-3 fatty acids and anteistrogens may emerge as a promising, effective, and safe chemopreventive strategy to be tested in a large multi-institutional trial using breast cancer incidence as the primary endpoint.

  14. ACETYLSALICYLIC ACID IN LOW DOSES FOR SECONDARY PREVENTION OF CARDIO-VASCULAR COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    N. A. Dmitrieva

    2009-01-01

    Full Text Available Data of evidence based medicine which confirm efficacy of acetylsalicylic acid (ACA in cardiologic practice are presented. The special attention is given to generic drugs of ACA. Their application has increased essentially recently. Some of generics are comparable with original drugs on clinical efficacy but have economic advantages.

  15. Prevention of topical surfactant-induced itch-related responses by chlorogenic acid through the inhibition of increased histamine production in the epidermis.

    Science.gov (United States)

    Inami, Yoshihiro; Andoh, Tsugunobu; Kuraishi, Yasushi

    2013-01-01

    Effects of chlorogenic acid on surfactant-induced itching were studied in mice. Topical application of sodium laurate increased hind-paw scratching, an itch-related response, 2 h after application, which was inhibited by topical post-treatment with chlorogenic acid. Sodium laurate increased the histamine content and 53-kDa L-histidine decarboxylase in the epidermis, which were also inhibited by post-treatment with chlorogenic acid. These results suggest that topical chlorogenic acid is effective in the prevention of itching induced by anionic surfactants. The inhibitory activity of chlorogenic acid may be due to the inhibition of an increase in histamine in the epidermis.

  16. Cyclic GMP signaling in cardiomyocytes modulates fatty acid trafficking and prevents triglyceride accumulation.

    Science.gov (United States)

    Khairallah, Ramzi J; Khairallah, Maya; Gélinas, Roselle; Bouchard, Bertrand; Young, Martin E; Allen, Bruce G; Lopaschuk, Gary D; Deschepper, Christian F; Des Rosiers, Christine

    2008-08-01

    While the balance between carbohydrates and fatty acids for energy production appears to be crucial for cardiac homeostasis, much remains to be learned about the molecular mechanisms underlying this relationship. Given the reported benefits of cGMP signaling on the myocardium, we investigated the impact of its chronic activation on cardiac energy metabolism using mice overexpressing a constitutively active cytoplasmic guanylate cyclase (GC(+/0)) in cardiomyocytes. Ex vivo working GC(+/0) heart perfusions with (13)C-labeled substrates revealed an altered pattern of exogenous substrate fuel selection compared to controls, namely a 38+/-9% lower contribution of exogenous fatty acids to acetyl-CoA formation, while that of carbohydrates remains unchanged despite a two-fold increase in glycolysis. The lower contribution of exogenous fatty acids to energy production is not associated with changes in energy demand or supply (contractile function, oxygen consumption, tissue acetyl-CoA or CoA levels, citric acid cycle flux rate) or in the regulation of beta-oxidation (acetyl-CoA carboxylase activity, tissue malonyl-CoA levels). However, GC(+/0) hearts show a two-fold increase in the incorporation of exogenous oleate into triglycerides. Furthermore, the following molecular data are consistent with a concomitant increase in triglyceride hydrolysis: (i) increased abundance of hormone sensitive lipase (HSL) protein (24+/-11%) and mRNA (22+/-4%) as well as (ii) several phosphorylation events related to HSL inhibitory (AMPK) and activation (ERK 1/2) sites, which should contribute to enhance its activity. These changes in exogenous fatty acid trafficking in GC(+/0) hearts appear to be functionally relevant, as demonstrated by their resistance to fasting-induced triglyceride accumulation. While the documented metabolic profile of GC(+/0) mouse hearts is partly reminiscent of hypertrophied hearts, the observed changes in lipid trafficking have not been previously documented, and may

  17. Bone marrow-derived dendritic cells.

    Science.gov (United States)

    Roney, Kelly

    2013-01-01

    While much is understood about dendritic cells and their role in the immune system, the study of these cells is critical to gain a more complete understanding of their function. Dendritic cell isolation from mouse body tissues can be difficult and the number of cells isolated small. This protocol describes the growth of large number of dendritic cells from the culture of mouse bone marrow cells. The dendritic cells grown in culture facilitate experiments that may require large number of dendritic cells without great expense or use of large number of mice.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik; Jeong, Soyeon; Shin, Soyeon; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-01-30

    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.

  20. Effect of Oral Alpha Lipoic Acid in Preventing the Genesis of Canine Diabetic Cataract: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    David L. Williams

    2017-03-01

    Full Text Available Blinding cataract is a significant effect of canine diabetes with 75% of animals affected two years after diagnosis. Lens opacification occurs primarily through the generation of sorbitol, a sugar alcohol, through the action of aldose reductase (AR. The osmotic effect of sorbitol draws water into the lens, causing opacification. Inhibition of AR should thus prevent the generation of cataracts. A topical AR inhibitor has been shown to have this effect, as has the commercially available neutraceutical OcuGLO, containing the AR inhibitor alpha lipoic acid (ALA together with other plant-based antioxidants. Here a comparison is made between the number of diabetic dogs developing cataracts when given oral ALA alone and those given a mix containing ascorbic acid and tocopherol. Animals given ALA developed significantly fewer lens opacities than those given conventional antioxidants. Cataracts which formed occurred at a significantly greater duration after the commencement of treatment than those on the antioxidant mix. Although this is a small study conducted over a short period, the significant benefit of ALA in diabetic dogs is a reason to evaluate these effects in larger trials. As AR is involved in diabetic retinopathy and neuropathy, this enzyme inhibitor may be worthy of evaluation in preventing these conditions in human diabetics also.

  1. Molecular Mechanisms of Induction of Tolerant and Tolerogenic Intestinal Dendritic Cells in Mice.

    Science.gov (United States)

    Steimle, Alex; Frick, Julia-Stefanie

    2016-01-01

    How does the host manage to tolerate its own intestinal microbiota? A simple question leading to complicated answers. In order to maintain balanced immune responses in the intestine, the host immune system must tolerate commensal bacteria in the gut while it has to simultaneously keep the ability to fight pathogens and to clear infections. If this tender equilibrium is disturbed, severe chronic inflammatory reactions can result. Tolerogenic intestinal dendritic cells fulfil a crucial role in balancing immune responses and therefore creating homeostatic conditions and preventing from uncontrolled inflammation. Although several dendritic cell subsets have already been characterized to play a pivotal role in this process, less is known about definite molecular mechanisms of how intestinal dendritic cells are converted into tolerogenic ones. Here we review how gut commensal bacteria interact with intestinal dendritic cells and why this bacteria-host cell interaction is crucial for induction of dendritic cell tolerance in the intestine. Hereby, different commensal bacteria can have distinct effects on the phenotype of intestinal dendritic cells and these effects are mainly mediated by impacting toll-like receptor signalling in dendritic cells.

  2. Hypoxia-inducible factor-1a contributes to dendritic overgrowth in tuberous sclerosis.

    Science.gov (United States)

    Zhang, Longbo; Feliciano, David M; Huang, Tianxiang; Zhang, Shiliang; Bordey, Angélique

    2016-01-26

    Expression of hypoxia-inducible factor 1a (HIF1a) is increased under several pathological conditions such as hyperactive mechanistic target of rapamycin complex 1 (mTORC1) in tuberous sclerosis complex (TSC). Hyperactive mTORC1 and the resulting increased dendritic complexity of neurons are shared molecular and cellular alterations in several neurological disorders associated with cognitive disabilities. Despite some evidence that HIF1a contributes to dendritic overgrowth in vitro, it remains unknown whether increased HIF1a in TSC neurons could contribute to their increased dendritic complexity. To address this use in vivo, we generated TSC neurons by deleting Tsc1 in newborn olfactory bulb (OB) neurons of conditional Tsc1 transgenic mice using neonatal electroporation. In addition to their increased dendritic complexity, Tsc1(null) neurons have been reported to display increased Hif1a mRNA level and HIF1a transcriptional activity. We found that Tsc1(null)-dependent dendritic overgrowth was prevented by knocking down HIF1a or expressing a dominant negative HIF1a. In addition, overexpressing HIF1a in wild-type developing neurons resulted in increased dendritic complexity in vivo. These data highlight that an increase in HIF1a levels contributes to abnormal dendritic patterning in developing neurons under normal conditions and hyperactive mTORC1 conditions as in TSC.

  3. Gluconic acid-producing Pseudomonas sp. prevent γ-actinorhodin biosynthesis by Streptomyces coelicolor A3(2).

    Science.gov (United States)

    Galet, Justine; Deveau, Aurélie; Hôtel, Laurence; Leblond, Pierre; Frey-Klett, Pascale; Aigle, Bertrand

    2014-09-01

    Streptomyces are ubiquitous soil bacteria well known for their ability to produce a wide range of secondary metabolites including antibiotics. In their natural environments, they co-exist and interact with complex microbial communities and their natural products are assumed to play a major role in mediating these interactions. Reciprocally, their secondary metabolism can be influenced by the surrounding microbial communities. Little is known about these complex interactions and the underlying molecular mechanisms. During pairwise co-culture experiments, a fluorescent Pseudomonas, Pseudomonas fluorescens BBc6R8, was shown to prevent the production of the diffusible blue pigment antibiotic γ-actinorhodin by Streptomyces coelicolor A3(2) M145 without altering the biosynthesis of the intracellular actinorhodin. A mutant of the BBc6R8 strain defective in the production of gluconic acid from glucose and consequently unable to acidify the culture medium did not show any effect on the γ-actinorhodin biosynthesis in contrast to the wild-type strain and the mutant complemented with the wild-type allele. In addition, when glucose was substituted by mannitol in the culture medium, P. fluorescens BBc6R8 was unable to acidify the medium and to prevent the biosynthesis of the antibiotic. All together, the results show that P. fluorescens BBc6R8 impairs the biosynthesis of the lactone form of actinorhodin in S. coelicolor by acidifying the medium through the production of gluconic acid. Other fluorescent Pseudomonas and the opportunistic pathogen Pseudomonas aeruginosa PAO1 also prevented the γ-actinorhodin production in a similar way. We propose some hypotheses on the ecological significance of such interaction.

  4. The Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Trial – Rationale and Design

    Science.gov (United States)

    Mozaffarian, Dariush; Marchioli, Roberto; Gardner, Tim; Ferrazzi, Paolo; O’Gara, Patrick; Latini, Roberto; Libby, Peter; Lombardi, Federico; Macchia, Alejandro; Page, Richard; Santini, Massimo; Tavazzi, Luigi; Tognoni, Gianni

    2011-01-01

    Post-operative atrial fibrillation/flutter (PoAF) commonly complicates cardiac surgery, occurring in 25–60% of patients. PoAF is associated with significant morbidity, higher long-term mortality, and increased healthcare costs. Novel preventive therapies are clearly needed. In experiments and short-term trials, seafood-derived long-chain omega-3 polyunsaturated fatty acids (PUFA) influence several risk factors that might reduce risk of PoAF. A few small and generally underpowered trials have evaluated effects of omega-3-PUFA supplementation on PoAF, with mixed results. The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) trial is an appropriately powered, investigator-initiated, randomized, double-blind, placebo-controlled, multinational trial to determine whether peri-operative oral omega-3-PUFA reduces occurrence of PoAF in 1,516 patients undergoing cardiac surgery. Additional aims include evaluation of resource utilization, biologic pathways and mechanisms, postoperative cognitive decline, and safety. Broad inclusion criteria encompass a real-world population of outpatients and inpatients scheduled for cardiac surgery. Treatment comprises a total pre-operative loading dose of 8–10 g of omega-3-PUFA or placebo divided over 2–5 days, followed by 2 g/d until hospital discharge or post-operative day 10, whichever first. Based on anticipated 30% event rate in controls, total enrollment of 1,516 patients (758 per treatment arm) will provide 90% power to detect 25% reduction in PoAF. OPERA will provide invaluable evidence to inform biologic pathways, proof-of-concept that omega-3-PUFA influence cardiac arrhythmias, and potential regulatory standards and clinical use of this simple, inexpensive, and low-risk intervention to prevent PoAF. PMID:21742090

  5. Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

    Science.gov (United States)

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2013-12-05

    Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth.

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

    OpenAIRE

    Maria Mäkitalo; Christian Maurice; Yu Jia; Björn Öhlander

    2014-01-01

    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 sulphi...

  7. Evidence that dendritic mitochondria negatively regulate dendritic branching in pyramidal neurons in the neocortex.

    Science.gov (United States)

    Kimura, Toshiya; Murakami, Fujio

    2014-05-14

    The precise branching patterns of dendritic arbors have a profound impact on information processing in individual neurons and the brain. These patterns are established by positive and negative regulation of the dendritic branching. Although the mechanisms for positive regulation have been extensively investigated, little is known about those for negative regulation. Here, we present evidence that mitochondria located in developing dendrites are involved in the negative regulation of dendritic branching. We visualized mitochondria in pyramidal neurons of the mouse neocortex during dendritic morphogenesis using in utero electroporation of a mitochondria-targeted fluorescent construct. We altered the mitochondrial distribution in vivo by overexpressing Mfn1, a mitochondrial shaping protein, or the Miro-binding domain of TRAK2 (TRAK2-MBD), a truncated form of a motor-adaptor protein. We found that dendritic mitochondria were preferentially targeted to the proximal portion of dendrites only during dendritic morphogenesis. Overexpression of Mfn1 or TRAK2-MBD depleted mitochondria from the dendrites, an effect that was accompanied by increased branching of the proximal portion of the dendrites. This dendritic abnormality cannot be accounted for by changes in the distribution of membrane trafficking organelles since the overexpression of Mfn1 did not alter the distributions of the endoplasmic reticulum, Golgi, or endosomes. Additionally, neither did these constructs impair neuronal viability or mitochondrial function. Therefore, our results suggest that dendritic mitochondria play a critical role in the establishment of the precise branching pattern of dendritic arbors by negatively affecting dendritic branching.

  8. Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole

    Directory of Open Access Journals (Sweden)

    Sun SL

    2016-10-01

    Full Text Available Shengliang Sun,* Fuchao Wang,* Honglei Dou, Longqiang Zhang, Jiwen Li Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong, People’s Republic of China *These authors contributed equally to this work Background: This study aims to compare the efficacy and safety between zoledronic acid combined with calcium and calcium alone to prevent aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole.Methods: One hundred twenty patients were randomly divided into two groups, A and B. Patients in group A (n=60 received modified radical mastectomy or breast-conserving surgery + four cycles of AC followed by T regimen (optional + radiotherapy (optional + letrozole 2.5 mg daily + calcium 500 mg twice daily + vitamin D 400 international units daily +4 mg of zoledronic acid every 6 months, while patients in group B (n=60 were not given zoledronic acid and the rest of the treatments of group B were the same as group A. All the patients were followed up for 1 year. The primary endpoint was the intrapatient percentage change in lumbar spine (LS bone mineral density (BMD from baseline to month 12. Secondary endpoints included the percentage change in total hip (TH and femoral neck (FN BMD, the incidence of osteoporosis, the incidence of a clinically meaningful 5% decline in BMD at 1 year, change of serum N-telopeptide of type 1 collagen (NTX and bone-specific alkaline phosphatase (BSAP concentrations.Results: Patients in group A had a statistically significant higher average change and average percent change in LS, FN, and TH than group B. Group A had a statistically significant lower incidence of a clinically meaningful loss of bone density at the LS, FN, or TH than Group B. The incidence of osteoporosis in group A was significantly lower than group B. The decreases in NTX and BSAP concentrations from baseline to month 12 in patients of group A were significant; in contrast

  9. Knowledge and use of folic acid for birth defect prevention among women of childbearing age in Shanghai, China: a prospective cross-sectional study.

    Science.gov (United States)

    Lian, Huan; Ma, Duan; Zhou, Shu-Feng; Li, Xiaotian

    2011-12-01

    This study aimed to assess the knowledge, attitude, and practice of folic acid intake for prevention of birth defects in Chinese women of child-bearing age. In this prospective cross-sectional study, a total of 1,338 women aged 20-45 years were randomly selected for interview. Data on folic acid knowledge and information on folic acid intake in the subjects were collected. Age, education, contraception, and status of family planning were used as the independent variables in multivariate logistic regression. 55.6% of the subjects took contraception at all times, and 33.9% had pregnancy planning in the next six months. 49.7% of the interviewed women knew the benefits of folic acid and 34.6% realized the correct time of folic acid intake; and 14.9% of these women actually took folic acid daily. Planning to be pregnant in the next six months was associated with knowledge of folic acid benefits, correct time of folic acid intake and actual intake. A higher education level was correlated with the knowledge of folic acid benefits and correct time of folic acid intake, but was not linked to actual intake of folic acid. The knowledge and use of folic acid were at low to moderate levels in women at childbearing age in Shanghai, China, and general knowledge of folic acid benefits and correct time of folic acid intake should be conveyed to these women.

  10. Administration of ascorbic acid to prevent bleaching-induced tooth sensitivity: a randomized triple-blind clinical trial.

    Science.gov (United States)

    de Paula, E A; Kossatz, S; Fernandes, D; Loguercio, A D; Reis, A

    2014-01-01

    This study evaluated the effect of ascorbic acid, 500 mg every eight hours, on bleaching-induced tooth sensitivity. A triple-blind, parallel design, and placebo-controlled randomized clinical trial was conducted on 39 adults. The pills (placebo or ascorbic acid) were administered three times per day for 48 hours; the first dose was given one hour prior to each bleaching session. Two bleaching sessions with 35% hydrogen peroxide gel were performed with a one-week interval. Tooth sensitivity was recorded up to 48 hours after bleaching. The color evaluation was performed before and 30 days after bleaching. The absolute risk and intensity of tooth sensitivity were evaluated by Fisher exact and Mann-Whitney U-tests, respectively. Color changes were evaluated by unpaired t-test (α=0.05). There were no significant differences in the absolute risk and intensity of tooth sensitivity and color change between the groups. Both groups showed a similar risk of tooth sensitivity (p>0.05). The perioperative use of an antioxidant, such as ascorbic acid (500 mg, three times daily) perorally, was not able to prevent bleaching-induced tooth sensitivity or reduce its intensity.

  11. Improvement of glassy sol-gel sensors for preventive conservation of historical materials against acidity

    Directory of Open Access Journals (Sweden)

    Carmona, N.

    2007-08-01

    Full Text Available Sensors based on sol-gel glassy coatings doped with 2[4-(dimethyl-amino phenylazo] benzoic acid are able to change their optical absorption when they are submitted to different concentration of H3O+ and OH-. The sensors behaviour in field tests was studied in Cracow (Poland, varying the normal procedure of operation to improve their response. Both the sensors optical parameters and the environmental conditions (temperature, humidity, pressure, SO2 and NOx concentrations were measured. The sensors response was analysed in terms of their visible absorbance changes, which are due to local neutralisation reactions in the sensors surface by the join effect of acid pollutants and humidity. Correlations between the main acid pollutant (SO2 concentration and the sensors response are established to provide a relation between the optical absorption and the environmental pH. The sensors are able to detect and monitorise environmental acidity, as well as to alert on the pollutant concentration that may damage most of the historical materials.

    Los sensores a base de recubrimientos vítreos sol-gel dopados con ácido 2[4-(dimetil-amino fenilazo] benzoico son capaces de cambiar su absorción óptica cuando se someten a distintas concentraciones de iones H3O+ y OH-. La respuesta de los sensores en ensayos de campo se estudió en Cracovia (Polonia variando el procedimiento normal de uso, con el fin de mejorar su respuesta. Se midieron tanto los parámetros ópticos de los sensores como las condiciones ambientales (temperatura, humedad, presión y concentraciones de SO2 y de NOx. La respuesta de los sensores se analizó en términos de los cambios de su absorción visible. Dichos cambios se deben a reacciones locales de neutralización que tienen lugar en la superficie de los sensores, debido al efecto conjunto de los contaminantes de carácter ácido y a la humedad ambiental. Se establecieron correlaciones entre la concentración del contaminante

  12. Neonatal striatal grafts prevent lethal syndrome produced by bilateral intrastriatal injection of kainic acid.

    Science.gov (United States)

    Tulipan, N; Huang, S; Whetsell, W O; Allen, G S

    1986-07-02

    It is reported that unilateral grafts of neonatal striatal tissue protect the recipient from the lethal aphagia and adipsia produced by bilateral intrastriatal injection of 10 nmol of kainic acid in rats. It is shown that neither adult striatum nor neonatal tissue from other sites have the same lifesaving effect and that the salutary effect of the graft is dependent upon graft survival. Grafts from a histoincompatible donor are apparently rejected, leading to the death of the recipient. Cyclosporine inhibits rejection thereby enabling recipient survival. It is postulated that the graft exerts a neurohumoral influence that protects the striatum from the toxic effect of kainate.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. [Awareness and knowledge of the use of folic acid in the prevention of neural tube defects: a survey of women living in Santiago, Chile].

    Science.gov (United States)

    Pardo V, Rosa A; Lay-Son R, Guillermo; Aranda Ch, Waldo; Dib M, Martín; Espina M, Pablo; Muñoz K, María J; Muñoz B, Pilar; Navarrete C, María F; Ojeda M, Natalia V; Parra, Jorge; Rebolledo D, Cristian A; Recabal G, Pedro; Tenhamm T, Tamara

    2007-12-01

    Wheat flour in Chile is fortified with folie acid and pregnant women are also supplemented with the vitamin, but the population level of knowledge or awareness about this vitamin and its use by pregnant women is unknown. To assess the level of knowledge that postpartum women from Santiago de Chile have about folic acid. A questionnaire about folic acid and its effects on the prevention of neural tube defects was developed adapting questionnaires designed abroad. It was applied by medical students to puerperal women, hospitalized in public hospitals. The questionnaire was applied to 342 women aged 26 +/- 7 years. Sixty one percent were housewives and 55% completed high school education. Forty seven percent of these women had heard about folic acid, 9.6% knew that it was able to prevent congenital defects and only one received an adequate supplementation during pregnancy. Women aged 25 to 34 years and those with an adequate medical care during pregnancy had a significantly better knowledge about folic acid and its role in the prevention of congenital anomalies. The more common means to receive information about folic acid were midwives (34%), mass media (28%) and doctors (20%). Two hundred eleven women (62%) agreed to take folic acid in a future gestation and 58% preferred to do so using fortified foods. Post partum women from Santiago have a poor knowledge about the relevance of folic acid supplementation.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. A Wood-Waste Cover Prevents Sulphide Oxidation and Treats Acid Effluents at the East-Sullivan Mine Site

    Science.gov (United States)

    Germain, D.; Tassé, N.; Cyr, J.

    2004-05-01

    At the East Sullivan site, wood wastes covering the abandoned mine tailings impoundment prevent sulphide oxidation by creating an anoxic environment. The addition of coarse ligneous wastes favours infiltration, resulting in a water table rise. This maintains most tailings saturated and thus provides an additional protection against sulphide oxidation. Moreover, high infiltration allows a more rapid flushing of acid prone groundwater generated prior to the cover placement. Finally, the pore-waters under the cover are characterized by a strong reducing potential and high alkalinity. These conditions favour sulphate reduction and base metal precipitation as sulphides and carbonates. The restoration strategy capitalized on the alkaline and reductive properties of the waters underlying the wood-waste cover. An original treatment of acid effluents, based on the recirculation of water discharging around the impoundment through the organic cover, was implemented in 1998. In 2003, the total volume of water treated was 725 000 m3. Data gathered near the dispersal zone show that despite dispersing acid water, the groundwater pH decreases by only one unit from 7 to 6, during the recirculation period: May to October. However, alkalinity decreases from 800 to 100 mg/L-CaCO3. But it is back up to 800 mg/L the following spring, thanks to sulphate reduction. Fe2+ concentrations near the dispersal zone are maintained below 2 mg/L. Evolution of the iron mass in the surface waters suggests that the contaminated groundwater flush is completed in the north and west sectors of the impoundment; the east and south ones are expected to be recovered within 3 to 4 years. A wood-waste cover, besides limiting sulphide oxidation, can fill the role of alkaline reducing barrier for the treatment of these acidogenic waters, until a balance between acidity and alkalinity in the effluent is reached.

  17. Knowledge and periconceptional use of folic acid for the prevention of neural tube defects in ethnic communities in the United Kingdom: systematic review and meta-analysis.

    Science.gov (United States)

    Peake, Jordana N; Copp, Andrew J; Shawe, Jill

    2013-07-01

    It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced sources published after 1991, the year of the landmark Medical Research Council's Vitamin Study, were included. A meta-analysis was performed of studies that assessed preconceptional folic acid use in Caucasians and non-Caucasians. Five studies met the inclusion criteria for assessment of knowledge and/or use of folic acid supplements in U.K. women including non-Caucasians. The available evidence indicates that South Asians specifically have less knowledge and lower periconceptional use of folic acid than Caucasians; one study found that West Indian and African women also had lower folic acid uptake. A synthesis of results from three of the studies, in a meta-analysis, shows that Caucasians are almost three times more likely to take folic acid before conception than non-Caucasians. From the limited evidence available, U.K. women of non-Caucasian ethnicity appear to have less knowledge and a lower uptake of folic acid supplementation than Caucasians during the periconceptional period. Implementing targeted, innovative education campaigns together with a mandatory fortification policy, including the fortification of ethnic minority foods, will be required for maximum prevention of folic acid-preventable NTDs across different ethnic groups. Copyright © 2013 Wiley Periodicals, Inc.

  18. Phase field modeling of dendritic coarsening during isothermal

    Directory of Open Access Journals (Sweden)

    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.

  19. Cost-Effectiveness of Zoledronic Acid to Prevent and Treat Postmenopausal Osteoporosis in Comparison with Routine Medical Treatment

    Science.gov (United States)

    Golmohamdi, Fateme Rostami; Abbasi, Mahnaz; Karyani, Ali Kazemi; Sari, Ali Akbari

    2016-01-01

    Introduction Fractures caused by osteoporosis are prevalent among elderly females, which reduce quality of life significantly. This study aimed at comparing cost-effectiveness of Zoledronic acid in preventing and treating post-menopause osteoporosis as compared with routine medical treatment. Methods This cost-effectiveness study was carried out retrospectively from the Ministry of Health and insurance organizations perspective. Costs were evaluated based on the cost estimation of a sample of patients. Outcomes were obtained from a systematic review. The Cost-Effectiveness Ratio (CER) and incremental cost-effectiveness ratio (ICER) for outcome of femoral neck Bone Mineral Density (BMD), hip trochanter BMD, total hip BMD and lumbar spine BMD and cost-benefit of consuming Zoledronic Acid were calculated for fracture outcome obtained from reviewing hospital records. Results The results and the ICER calculated for study outcomes indicated that one percent increase of BMD on femoral neck BMD requires further cost of $386. One percent increase of BMD on hip trochanter BMD requires further cost of $264. One percent increase of BMD on total hip BMD requires further cost of $388, one percent increase of BMD on lumbar spine BMD requires further cost of $347. The Cost Benefit Analysis (CBA) calculated for vertebral and hip fracture, non-vertebral fracture, any clinical fracture, and morphometric fracture for a 36-month period were about 0.82, 0.57, and 1.06, respectively. Vertebral and hip fractures, and non-vertebral fractures or any clinical fracture for a 12-month period were calculated as 1.14 and 0.64, respectively. In other words, Zoledronic acid consumption approach is a cheaper and better approach based on an economic assessment, and it can be considered as a dominant approach. Conclusion According to the cost-effectiveness of zoledronic acid in the prevention and treatment of osteoporosis in women, despite the costs, it is recommended that insurance coverage for the

  20. Regulation of AMPA and NMDA receptor-mediated EPSPs in dendritic trees of thalamocortical cells.

    Science.gov (United States)

    Lajeunesse, Francis; Kröger, Helmut; Timofeev, Igor

    2013-01-01

    Two main excitatory synapses are formed at the dendritic arbor of first-order nuclei thalamocortical (TC) neurons. Ascending sensory axons primarily establish contacts at large proximal dendrites, whereas descending corticothalamic fibers form synapses on thin distal dendrites. With the use of a multicomparment computational model based on fully reconstructed TC neurons from the ventroposterolateral nucleus of the cat, we compared local responses at the site of stimulation as well as somatic responses induced by both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and N-methyl-D-aspartate receptor (NMDAR)-mediated currents. We found that AMPAR-mediated responses, when synapses were located at proximal dendrites, induced a larger depolarization at the level of soma, whereas NMDAR-mediated responses were more efficient for synapses located at distal dendrites. The voltage transfer and transfer impedance were higher for NMDAR than for AMPAR activation at any location. For both types of synaptic current and for both input locations at the dendritic arbor, somatic responses were characterized by a low variability despite the large variability found in local responses in dendrites. The large neurons had overall smaller somatic responses than small neurons, but this relation was not found in local dendritic responses. We conclude that in TC cells, the dendritic location of small synaptic inputs does not play a major role in the amplitude of a somatic response, but the size of the neuron does. The variability of response amplitude between cells was much larger than the variability within cells. This suggests possible functional segregation of TC neurons of different size.

  1. Role of cis-Monounsaturated Fatty Acids in the Prevention of Coronary Heart Disease.

    Science.gov (United States)

    Joris, Peter J; Mensink, Ronald P

    2016-07-01

    The effects of cis-monounsaturated fatty acids (cis-MUFAs) on the risk of coronary heart disease (CHD) and on CHD mortality are not clear. Also, dietary recommendations for cis-MUFA as derived by various organizations are not in agreement. Earlier studies have mainly focused on the effects of cis-MUFA on serum lipids and lipoproteins. More recent studies, however, have also addressed effects of cis-MUFA on other non-traditional CHD risk markers such as vascular function markers, postprandial vascular function, and energy intake and metabolism. Although well-designed randomized controlled trials with CHD events as endpoints are missing, several large prospective cohort studies have recently been published on the relationship between cis-MUFA and CHD risk. The aim of this paper is to review these new studies that have been published in the last 3 years on the effects of cis-MUFA on cardiovascular risk markers and CHD.

  2. Future opportunities in preventing ototoxicity: Caffeic acid phenethyl ester may be a candidate (Review).

    Science.gov (United States)

    Akyol, Sumeyya; Isik, Bunyamin; Altuntas, Aynur; Erden, Gonul; Cakmak, Ozlem; Kurşunlu, S Fatih; Adam, Bahattin; Akyol, Omer

    2015-09-01

    Caffeic acid phenethyl ester (CAPE) is an important active component of propolis, which is derived from honeybee hives. It has received increasing attention in a variety of medical and pharmaceutical research, due to its anti‑oxidant, antiproliferative, anti‑inflammatory, antiviral and antifungal activity, in addition to its antineoplastic properties. Besides the use of CAPE as an antioxidant and anti‑inflammatory agent in a number of in vivo studies of ear disease, its beneficial effects have been reported in the treatment of cancer, arthritis, allergies, heart disease, diabetes, kidney disease, liver disease and neurological disease. CAPE influences a number of biochemical pathways, as well as several targets involved in ear diseases, in particular, in ototoxicity. The protective effects of CAPE in ototoxicity, which may be induced by a number factors, including lipopolysaccharides, hydrogen peroxide and streptomycin, are evaluated and discussed in the present review.

  3. Salvianolic acid A, a novel matrix metalloproteinase-9 inhibitor, prevents cardiac remodeling in spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Baohong Jiang

    Full Text Available Cardiac fibrosis is a deleterious consequence of hypertension which may further advance to heart failure and increased matrix metalloproteinase-9 (MMP-9 contributes to the underlying mechanism. Therefore, new therapeutic strategies to attenuate the effects of MMP-9 are urgently needed. In the present study, we characterize salvianolic acid A (SalA as a novel MMP-9 inhibitor at molecular, cellular and animal level. We expressed a truncated form of MMP-9 which contains only the catalytic domain (MMP-9 CD, and used this active protein for enzymatic kinetic analysis and Biacore detection. Data generated from these assays indicated that SalA functioned as the strongest competitive inhibitor of MMP-9 among 7 phenolic acids from Salvia miltiorrhiza. In neonatal cardiac fibroblast, SalA inhibited fibroblast migration, blocked myofibroblast transformation, inhibited secretion of intercellular adhesion molecule (ICAM, interleukin-6 (IL-6 and soluble vascular cell adhesion molecule-1 (sVCAM-1 as well as collagen induced by MMP-9 CD. Functional effects of SalA inhibition on MMP-9 was further confirmed in cultured cardiac H9c2 cell overexpressing MMP-9 in vitro and in heart of spontaneously hypertensive rats (SHR in vivo. Moreover, SalA treatment in SHR resulted in decreased heart fibrosis and attenuated heart hypertrophy. These results indicated that SalA is a novel inhibitor of MMP-9, thus playing an inhibitory role in hypertensive fibrosis. Further studies to develop SalA and its analogues for their potential clinical application of cardioprotection are warranted.

  4. Salvianolic Acid A, a Novel Matrix Metalloproteinase-9 Inhibitor, Prevents Cardiac Remodeling in Spontaneously Hypertensive Rats

    Science.gov (United States)

    Deng, Yanping; Teng, Fukang; Chen, Jing; Xue, Song; Kong, Xiangqian; Luo, Cheng; Shen, Xu; Jiang, Hualiang; Xu, Feng; Yang, Wengang; Yin, Jun; Wang, Yanhui; Chen, Hui; Wu, Wanying; Liu, Xuan; Guo, De-an

    2013-01-01

    Cardiac fibrosis is a deleterious consequence of hypertension which may further advance to heart failure and increased matrix metalloproteinase-9 (MMP-9) contributes to the underlying mechanism. Therefore, new therapeutic strategies to attenuate the effects of MMP-9 are urgently needed. In the present study, we characterize salvianolic acid A (SalA) as a novel MMP-9 inhibitor at molecular, cellular and animal level. We expressed a truncated form of MMP-9 which contains only the catalytic domain (MMP-9 CD), and used this active protein for enzymatic kinetic analysis and Biacore detection. Data generated from these assays indicated that SalA functioned as the strongest competitive inhibitor of MMP-9 among 7 phenolic acids from Salvia miltiorrhiza. In neonatal cardiac fibroblast, SalA inhibited fibroblast migration, blocked myofibroblast transformation, inhibited secretion of intercellular adhesion molecule (ICAM), interleukin-6 (IL-6) and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as collagen induced by MMP-9 CD. Functional effects of SalA inhibition on MMP-9 was further confirmed in cultured cardiac H9c2 cell overexpressing MMP-9 in vitro and in heart of spontaneously hypertensive rats (SHR) in vivo. Moreover, SalA treatment in SHR resulted in decreased heart fibrosis and attenuated heart hypertrophy. These results indicated that SalA is a novel inhibitor of MMP-9, thus playing an inhibitory role in hypertensive fibrosis. Further studies to develop SalA and its analogues for their potential clinical application of cardioprotection are warranted. PMID:23533637

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

    Science.gov (United States)

    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.

  6. Dendritic cells and contact dermatitis.

    Science.gov (United States)

    Sasaki, Yoshinori; Aiba, Setsuya

    2007-10-01

    Contact dermatitis is a biological response to simple chemicals in the skin. Although it is well known that allergic contact dermatitis is mediated by the immune system, it is still uncertain whether it is a kind of protective response or it is simply an unnecessary response. We have demonstrated the following: (1) haptens activate Langerhans cells in the initiation phase of murine allergic contact dermatitis in vivo, (2) haptens activate human monocyte-derived dendritic cells in vitro, (3) the activation of dendritic cells by haptens is primarily mediated by the activation of p38 mitogen-activated protein kinase (MAPK), and (4) the activation of p38 MAPK is mediated by stimulation related to an imbalance of intracellular redox. Based on these observations, we will discuss the biological significance of contact dermatitis. In addition, we will review some up-to-date findings on Langerhans cell biology.

  7. Lipid dynamics at dendritic spines.

    Science.gov (United States)

    Dotti, Carlos Gerardo; Esteban, Jose Antonio; Ledesma, María Dolores

    2014-01-01

    Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

  8. Salicylic acid improves the salinity tolerance of Medicago sativa in symbiosis with Sinorhizobium meliloti by preventing nitrogen fixation inhibition.

    Science.gov (United States)

    Palma, F; López-Gómez, M; Tejera, N A; Lluch, C

    2013-07-01

    In this work we have investigated the contribution of pretreatment with 0.1 and 0.5mM salicylic acid (SA) to the protection against salt stress in root nodules of Medicago sativa in symbiosis with Sinorhizobium meliloti. SA alleviated the inhibition induced by salinity in the plant growth and photosynthetic capacity of M. sativa-S. meliloti symbiosis. In addition, SA prevented the inhibition of the nitrogen fixation capacity under salt stress since nodule biomass was not affected by salinity in SA pretreated plants. Antioxidant enzymes peroxidase (POX), superoxide dismutase (SOD), ascorbate peroxidase (APX), dehidroascorbate reductase (DHAR) and glutathione reductase (GR), key in the main pathway that scavenges H2O2 in plants, were induced by SA pretreatments which suggest that SA may participate in the redox balance in root nodules under salt stress. Catalase activity (CAT) was inhibited around 40% by SA which could be behind the increase of H2O2 detected in nodules of plants pretreated with SA. The accumulation of polyamines (PAs) synthesized in response to salinity was prevented by SA which together with the induction of 1-aminocyclopropane-l-carboxylic acid (ACC) content suggest the prevalence of the ethylene signaling pathway induced by SA in detriment of the synthesis of PAs. In conclusion, SA alleviated the negative effect of salt stress in the M. sativa-S. meliloti symbiosis through the increased level of nodule biomass and the induction of the nodular antioxidant metabolism under salt stress. The H2O2 accumulation and the PAs inhibition induced by SA in nodules of M. sativa suggest that SA activates a hypersensitive response dependent on ethylene.

  9. Microtubules in Dendritic Spine Development

    OpenAIRE

    2008-01-01

    It is generally believed that only the actin cytoskeleton resides in dendritic spines and controls spine morphology and plasticity. Here we report that microtubules (MTs) are present in spines and that shRNA knockdown of the MT-plus end binding protein EB3 significantly reduces spine formation. Furthermore, stabilization and inhibition of MTs by low doses of taxol and nocodazole enhance and impair spine formation elicited by BDNF, respectively. Therefore, MTs play an important role in the con...

  10. Melanoma immunotherapy: dendritic cell vaccines

    OpenAIRE

    Lozada-Requena, Ivan; Laboratorios de Inmunología #108, Laboratorio de investigación y Desarrollo, Facultad de Ciencieas y Filosofía, Universidad Cayetano Heredia. Lima, Perú Empresa de Investigación y Desarrollo en Cáncer (EMINDES) SAC. Lima, Perú.; Núñez, César; Empresa de Investigación y Desarrollo en Cáncer (EMINDES) SAC. Lima, Perú.; Aguilar, José Luis; Laboratorios de Inmunología #108, Laboratorio de investigación y Desarrollo, Facultad de Ciencieas y Filosofía, Universidad Cayetano Heredia. Lima, Perú.

    2015-01-01

    This is a narrative review that shows accessible information to the scientific community about melanoma and immunotherapy.Dendritic cells have the ability to participate in innate and adaptive immunity, but are not unfamiliar to the immune evasion oftumors. Knowing the biology and role has led to generate in vitro several prospects of autologous cell vaccines against diversetypes of cancer in humans and animal models. However, given the low efficiency they have shown, we must implementstrateg...

  11. Development of Dendritic Cell System

    Institute of Scientific and Technical Information of China (English)

    LiWu; AleksandarDakic

    2004-01-01

    The dendritic cell system contains conventional dendritic cells (DCs) and plasmacytoid pre-dendritic cells (pDCs). Both DCs and pDCs are bone marrow derived calls. Although the common functions of DCs are antigen-processing and T-lymphocyte activation, they differ in surface markers, migratory patterns, and cytokine output. These differences can determine the fate of the T cells they activate. Several subsets of mature DCs have been described in both mouse and human and the developmental processes of these specialized DC subsets have been studied extensively. The original concept that all DCs were of myeloid origin was questioned by several recent studies, which demonstrated that in addition to the DCs derived from myeloid precursors, some DCs could also be efficiently generated from lymphoid-restricted precursors. Moreover, it has been shown recently that both conventional DCs and pDCs can be generated by the Fit3 expressing hemopoietic progenitors regardless of their myeloid- or lymphoid-origin. These findings suggest an early developmental flexibility of precursors for DCs and pDCs. This review summarizes some recent observations on the development of DC system in both human and mouse. Cellular & Molecular Immunology. 2004;1(2):112-118.

  12. Development of Dendritic Cell System

    Institute of Scientific and Technical Information of China (English)

    Li Wu; Aleksandar Dakic

    2004-01-01

    The dendritic cell system contains conventional dendritic cells (DCs) and plasmacytoid pre-dendritic cells (pDCs). Both DCs and pDCs are bone marrow derived cells. Although the common functions of DCs are antigen-processing and T-lymphocyte activation, they differ in surface markers, migratory patterns, and cytokine output. These differences can determine the fate of the T cells they activate. Several subsets of mature DCs have been described in both mouse and human and the developmental processes of these specialized DC subsets have been studied extensively. The original concept that all DCs were of myeloid origin was questioned by several recent studies, which demonstrated that in addition to the DCs derived from myeloid precursors,some DCs could also be efficiently generated from lymphoid-restricted precursors. Moreover, it has been shown recently that both conventional DCs and pDCs can be generated by the Flt3 expressing hemopoietic progenitors regardless of their myeloid- or lymphoid-origin. These findings suggest an early developmental flexibility of precursors for DCs and pDCs. This review summarizes some recent observations on the development of DC system in both human and mouse.

  13. Tailor-made preventive medicine integrating amino acid checkup and its application toward disaster-stricken areas.

    Science.gov (United States)

    Kuroda, Masahiro; Tochikubo, Osamu

    2012-01-01

    ICT technologies for healthcare are useful in myriad locations for people with lifestyle-related illnesses and health irregularities. When symptoms turn into actual illnesses, it is difficult for them to be managed, and this situation is relevant for managing the health of victims after large-scale disasters; it is important to keep people healthy to prevent them from acquiring illness. This paper proposes a system of personalized preventive medicine for individuals to maintain their health and receive evidence-based feedback. We introduce general medical checkups, ubiquitous sensing, and plasma amino acid analysis as the system's core components. We evaluate these elements and discuss their applicability toward the disaster-stricken Tohoku area of Japan. This is an initial evaluation, but some functions are being used in the area. There are gaps between research results and actually deployable technologies, but it is important to use and improve the quality of life of victims who are ultimately forced to live in temporary housing for more than five years.

  14. Preventive Effect of Quercetin(A Flavonoid on Ulcerogenic of Acetyl Salisylic Acid in Rat’s Gastric Mucosa

    Directory of Open Access Journals (Sweden)

    M. Malek

    2004-10-01

    Full Text Available Lesion of the gastric mucosa is the most prevalent side effect of aspirin. Flavonoids with actions such as antioxidant, free radical scavenger and lipid peroxidant inhibitor can prevent mucosal lesion caused by aspirin. In this research effect of quercetin, as the most abundant flavonoid in human diet, was investigated on preventing ulcerogenic effect of aspirin or Acetyl Salisylic Acid(ASA.Eighteen male Wistar rats (220-330gr were randomly divided into 3 groups (6 in each group. In all groups consumption materials were adminstrated only once in acute form. First and second groups, as control groups, received ASA vehicle (1ml, orally and ASA suspension (300mg/kg, 1ml, orally respectively. The third group had a pretreatment with quercetin (200mg/kg half an hour before consumption of 300mg/kg ASA. After consumptiom the materials animals were kept 3hours, after that stomach was removed and was assessed for macroscopic and microscopis stomach mucosal lesions. Our results showed that, oral adminstration of ASA (300mg/kg caused considerable stomach mucosal lesions (P<0.05 and pretreatment with quercetin decreased the lesions (P<0.05. Therefore quercetin can be effecttive in protecting stomach mucosa against ulcers caused by ASA. Although the mechanism of quercetin action is not known, it might be used for mucosal protection with further investigations.

  15. Dendritic web silicon for solar cell application

    Science.gov (United States)

    Seidensticker, R. G.

    1977-01-01

    The dendritic web process for growing long thin ribbon crystals of silicon and other semiconductors is described. Growth is initiated from a thin wirelike dendrite seed which is brought into contact with the melt surface. Initially, the seed grows laterally to form a button at the melt surface; when the seed is withdrawn, needlelike dendrites propagate from each end of the button into the melt, and the web portion of the crystal is formed by the solidification of the liquid film supported by the button and the bounding dendrites. Apparatus used for dendritic web growth, material characteristics, and the two distinctly different mechanisms involved in the growth of a single crystal are examined. The performance of solar cells fabricated from dendritic web material is indistinguishable from the performance of cells fabricated from Czochralski grown material.

  16. Active dendrites enhance neuronal dynamic range.

    Directory of Open Access Journals (Sweden)

    Leonardo L Gollo

    2009-06-01

    Full Text Available Since the first experimental evidences of active conductances in dendrites, most neurons have been shown to exhibit dendritic excitability through the expression of a variety of voltage-gated ion channels. However, despite experimental and theoretical efforts undertaken in the past decades, the role of this excitability for some kind of dendritic computation has remained elusive. Here we show that, owing to very general properties of excitable media, the average output of a model of an active dendritic tree is a highly non-linear function of its afferent rate, attaining extremely large dynamic ranges (above 50 dB. Moreover, the model yields double-sigmoid response functions as experimentally observed in retinal ganglion cells. We claim that enhancement of dynamic range is the primary functional role of active dendritic conductances. We predict that neurons with larger dendritic trees should have larger dynamic range and that blocking of active conductances should lead to a decrease in dynamic range.

  17. Transcranial magnetic stimulation (TMS) inhibits cortical dendrites.

    Science.gov (United States)

    Murphy, Sean C; Palmer, Lucy M; Nyffeler, Thomas; Müri, René M; Larkum, Matthew E

    2016-03-18

    One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  19. Efficacy of oral nicotinic acid and choline in the treatment and prevention of fatty liver in dairy cow

    Institute of Scientific and Technical Information of China (English)

    TianWenru; YangDianjun; 等

    1994-01-01

    Nicotinic acid (N.C.)and choline were given orally to the periparturient cows to treat and prevent fatty liver.Blood parameters of glucose,β-hydroxybutyrate,albumin,total protein,magnesium,aspartate aminotransferase(AST) and non-esterified fatty acid(NEFA) were measured.There were no significant differences between the reated and untreated groups in the plasma concentrations of albumin,total,protein and magnsium.Significant decrease in plasma concentrations of β-hydroxybutyrate,NEFA and AST were observed in the treated cows following administration of N.C.and choline.All the fatty liver cows(100%) treated with N.C.and choline recovered within 5 weeks after calving compared with 71.4%(5/7) of untreated cows recovered.The incident ate of fatty liver postpartum in the cows with N.C.and choline given 2 weeks before calving was 30%(3/10),and the affected cows had a range of mild to moderate fatty liver whilst the incident rate was 50%(5/10)in the untreated cows.which had a range of mild to of severe fatty liver,Meanwhile,the treated cows had a significant higher prodection of milk and shorter intervals from calving to uterine involution,to the first postpartum ovulation and to conception.

  20. Effective prevention of chill-haze in beer using an acid proline-specific endoprotease from Aspergillus niger.

    Science.gov (United States)

    Lopez, Michel; Edens, Luppo

    2005-10-05

    Chill-haze formation during beer production is known to involve polyphenols that interact with proline-rich proteins. We hypothesized that incubating beer wort with a proline-specific protease would extensively hydrolyze these proline-rich proteins, yielding a peptide fraction that is unable to form a haze. Predigestion of the proline-rich wheat gliadin with different proteases pointed toward a strong haze-suppressing effect by a proline-specific enzyme. This finding was confirmed in small-scale brewing experiments using a recently identified proline-specific protease with an acidic pH optimum. Subsequent pilot plant trials demonstrated that, upon its addition during the fermentation phase of beer brewing, even low levels of this acidic enzyme effectively prevented chill-haze formation in bottled beer. Results of beer foam stability measurements indicated that the enzyme treatment leaves the beer foam almost unaffected. In combination with the enzyme's cost-effectiveness and regulatory status, these preliminary test results seem to favor further industrial development of this enzymatic beer stabilization method.

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

    Science.gov (United States)

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

    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.

  2. Common congenital anomalies: Environmental causes and prevention with folic acid containing multivitamins.

    Science.gov (United States)

    Sarmah, Swapnalee; Muralidharan, Pooja; Marrs, James A

    2016-09-01

    Congenital anomalies, congenital defects, or birth defects are significant causes of death in infants. The most common congenital defects are congenital heart defects (CHDs) and neural tube defects (NTDs). Defects induced by genetic mutations, environmental exposure to toxins, or a combination of these effects can result in congenital malformations, leading to infant death or long-term disabilities. These defects produce significant mortality and morbidity in the affected individuals, and families are affected emotional and financially. Also, society is impacted on many levels. Congenital anomalies may be reduced by dietary supplements of folic acid and other vitamins. Here, we review the evidence for specific roles of toxins (alcohol, cigarette smoke) in causing common severe congenital anomalies like CHDs, NTDs, and ocular defects. We also review the evidence for beneficial effects for dietary supplementation, and highlight gaps in our knowledge, where research may contribute to additional benefits of intervention that can reduce birth defects. Extensive discussion of common severe congenital anomalies (CHDs, NTDs, and ocular defects) illustrates the effects of diet on the frequency and severity of these defects. Birth Defects Research (Part C) 108:274-286, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. OMEGA-3 POLYUNSATURATED FATTY ACIDS IN ATRIAL FIBRILLATION PREVENTION AFTER SURGICAL MYOCARDIAL REVASCULARIZATION

    Directory of Open Access Journals (Sweden)

    A. V. Panov

    2008-01-01

    Full Text Available Aim. To estimate an efficacy of therapy with ω-3 polyunsaturated fatty acids (PUFA in patients with ischemic heart disease (IHD before and after coronary artery bypass graft (CABG.Material and methods. 189 patients (125 men, 64 women; aged 64,2±9,4 y.o. with IHD having indications to CABG were enrolled in the study. Patients of the first group (control had standard pre- and postoperative treatment. Patients of the second group received ω-3 PUFA (ОМАCОR, Solvay Pharma 2 g/daily in addition to standard therapy. Both groups were similar in clinical characteristics. ω-3 PUFA therapy started 7±4 day before CABG, renewed in early postoperative period (24-36 hours after surgery and lasted next 14 days. Efficacy of the therapy was estimated by atrial fibrillation frequency in postoperative period and time before hospital discharge after CABG. An automatic complex for transesophageal electrophysiological cardiac examination was used for the estimation of atrial conduction before and after CABG.Results. Omacor therapy in patients with ICD before CABG and in the early postoperative period reduces atrial fibrillation risk. It results in reduction of hemodynamic disorders and time before hospital discharge. Conclusion. Omacor therapy is safe and can be recommended to all patients going through CABG.

  5. Is prophylactic tranexamic acid administration effective and safe for postpartum hemorrhage prevention?

    Science.gov (United States)

    Li, Chunbo; Gong, Yuping; Dong, Lingling; Xie, Bingying; Dai, Zhiyuan

    2017-01-01

    Abstract Background: To assess the efficacy and safety of tranexamic acid (TA) in reducing blood loss and lowering transfusion needs for patients undergoing caesarean section (CS) or vaginal delivery (VD). Methods: An electronic literature search of PubMed, EMBASE, OVID, Cochrane library, Scopus, Central, and Clinical trials.gov was performed to identify studies that evaluating the usage of TA in CS or VD. The methodological quality of included trials was assessed and data extraction was performed. Results: Finally, 25 articles with 4747 participants were included. Our findings indicated TA resulted in a reduced intra-, postoperative, and total blood loss by a mean volume of 141.25 mL (95% confidence interval [CI] −186.72 to −95.79, P DVT) after CS or VD was associated with TA usage, while the minor side effects were more common. Conclusions: Our findings indicated that intravenous TA for patients undergoing CS was effective and safe. Although prophylactic TA administration is associated with reduced PPH, current existing data are insufficient to draw definitive recommendations about its clinical significance due to the poor to moderate quality of the included literatures. Thus, high-quality randomized controlled trials with larger samples are needed to validate our findings. PMID:28072700

  6. Prevention of valproic acid-induced neural tube defects by sildenafil citrate.

    Science.gov (United States)

    Tiboni, Gian Mario; Ponzano, Adalisa

    2015-08-15

    This study was undertaken to test the effects of sildenafil citrate (SC), a type 5 phosphodiesterase inhibitor, on valproic acid (VPA)-induced teratogenesis. On gestation day (GD) 8, ICR (CD-1) mice were treated by gastric intubation with SC at 0 (vehicle), 1.0, 2.5, 5.0 or 10mg/kg. One hour later, animals received a teratogenic dose of VPA (600mg/kg) or vehicle. Developmental endpoints were evaluated near the end of gestation. Twenty-eighth percent of fetuses exposed to VPA had neural tube defects (exencephaly). Pretreatment with SC at 2.5, 5.0 or 10mg/kg significantly reduced the rate of VPA-induced exencephaly to 15.9%, 13.7%, and 10.0%, respectively. Axial skeletal defects were observed in 75.8% of VPA-exposed fetuses. Pre-treatment with SC at 10mg/kg, but not at lower doses, significantly decreased the rate of skeletally affected fetuses to 61.6%. These results show that SC, which prolongs nitric oxide (NO) signaling action protects from VPA-induced teratogenesis.

  7. Enzyme responsive hyaluronic acid nanocapsules containing polyhexanide and their exposure to bacteria to prevent infection.

    Science.gov (United States)

    Baier, Grit; Cavallaro, Alex; Vasilev, Krasimir; Mailänder, Volker; Musyanovych, Anna; Landfester, Katharina

    2013-04-08

    Antibacterial nanodevices could bring coatings of plastic materials and wound dressings a big step forward if the release of the antibacterial agents could be triggered by the presence of the bacteria themselves. Here, we show that novel hyaluronic acid (HA)-based nanocapsules containing the antimicrobial agent polyhexanide are specifically cleaved in the presence of hyaluronidase, a factor of pathogenicity and invasion for bacteria like Staphylococcus aureus and Escherichia coli. This resulted in an efficient killing of the pathogenic bacteria by the antimicrobial agent. The formation of different polymeric nanocapsules was achieved through a polyaddition reaction in inverse miniemulsion. After the synthesis, the nanocapsules were transferred to an aqueous medium and investigated in terms of size, size distribution, functionality, and morphology using dynamic light scattering, zeta potential measurements and scanning electron microscopy. The enzyme triggered release of a model dye and the antimicrobial polyhexanide was monitored using fluorescence and UV spectroscopy. The stability of the nanocapsules in several biological media was tested and the interaction of nanocapsules with human serum protein was studied using isothermal titration calorimetry. The antibacterial effectiveness is demonstrated by determination of the antibacterial activity and determination of the minimal bactericidal concentration (MBC).

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  10. Dendritic Cells, New Tools for Vaccination

    Science.gov (United States)

    2003-01-01

    Review Dendritic cells , new tools for vaccination Jesus Colino, Clifford M. Snapper * Department of Pathology, Uniformed Services University of the...2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Keywords: Vaccines; Immunotherapy; Dendritic cells 1. Introduction During...DATE 2003 2. REPORT TYPE 3. DATES COVERED 00-00-2003 to 00-00-2003 4. TITLE AND SUBTITLE Dendritic cells , new tools for vaccination 5a

  11. Low Power Dendritic Computation for Wordspotting

    Directory of Open Access Journals (Sweden)

    Stephen Nease

    2013-05-01

    Full Text Available In this paper, we demonstrate how a network of dendrites can be used to build the state decoding block of a wordspotter similar to a Hidden Markov Model (HMM classifier structure. We present simulation and experimental data for a single line dendrite and also experimental results for a dendrite-based classifier structure. This work builds on previously demonstrated building blocks of a neural network: the channel, synapses and dendrites using CMOS circuits. These structures can be used for speech and pattern recognition. The computational efficiency of such a system is >10 MMACs/μW as compared to Digital Systems which perform 10 MMACs/mW.

  12. Neoplasms derived from plasmacytoid dendritic cells.

    Science.gov (United States)

    Facchetti, Fabio; Cigognetti, Marta; Fisogni, Simona; Rossi, Giuseppe; Lonardi, Silvia; Vermi, William

    2016-02-01

    Plasmacytoid dendritic cell neoplasms manifest in two clinically and pathologically distinct forms. The first variant is represented by nodular aggregates of clonally expanded plasmacytoid dendritic cells found in lymph nodes, skin, and bone marrow ('Mature plasmacytoid dendritic cells proliferation associated with myeloid neoplasms'). This entity is rare, although likely underestimated in incidence, and affects predominantly males. Almost invariably, it is associated with a myeloid neoplasm such as chronic myelomonocytic leukemia or other myeloid proliferations with monocytic differentiation. The concurrent myeloid neoplasm dominates the clinical pictures and guides treatment. The prognosis is usually dismal, but reflects the evolution of the associated myeloid leukemia rather than progressive expansion of plasmacytoid dendritic cells. A second form of plasmacytoid dendritic cells tumor has been recently reported and described as 'blastic plasmacytoid dendritic cell neoplasm'. In this tumor, which is characterized by a distinctive cutaneous and bone marrow tropism, proliferating cells derive from immediate CD4(+)CD56(+) precursors of plasmacytoid dendritic cells. The diagnosis of this form can be easily accomplished by immunohistochemistry, using a panel of plasmacytoid dendritic cells markers. The clinical course of blastic plasmacytoid dendritic cell neoplasm is characterized by a rapid progression to systemic disease via hematogenous dissemination. The genomic landscape of this entity is currently under intense investigation. Recurrent somatic mutations have been uncovered in different genes, a finding that may open important perspectives for precision medicine also for this rare, but highly aggressive leukemia.

  13. Prevention of lipopolysaccharide-induced injury by 3,5-dieaffeoylquinic acid in endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Ruo-peng ZHA; Wei XU; Wen-yi WANG; Li DONG; Yi-ping WANG

    2007-01-01

    Aim: To investigate the effect of 3,5-dicaffeoylquinic acid (3,5-diCQA) on lipopolysaccharide (LPS)-induced injury in human dermal microvascular endothe-lial cells (HMEC-1). Methods: The anti-oxidant effect was detected using the malondialdehyde (MDA) assay in a rat liver microsome model of lipid peroxidation.Cell viability was analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. Cell lipid peroxide injury was measured by lactate dehydrogenase (LDH) release. Apoptotic cells were detected by flow cytometry, and confirmed by DNA fragmentation analysis. Caspase-3 activity was measured using a specific assay kit. The level of intracellular reactive oxygen species (ROS) was determined by flow cytometry with a 2,7-dichlorodihydro-fluorescein diacetate fluorescence probe. Results: The exposure of microsomes to ascorbate-Fe2+ resulted in lipoperoxidation according to an increase in the level of MDA. MDA formation decreased in a dose-dependent manner on treatment with 5, 10, or 50 μmol/L 3,5-diCQA. Treatment with LPS for 16 h resulted in a 60% decrease in cell viability and an increase in LDH release from 47.6% to 61.5%. DNA laddering was observed by agarose gel electrophoresis. The level of apoptotic cells peaked at 27% after treatment with LPS for 12 h. Following treat-ment with LPS for 12 h, intracellular ROS and caspase-3 activity increased. Pre-treatment with 3,5-diCQA at 5, 10, or 50 μmol/L for 1 h attenuated LPS-mediated endothelial cell injury. The anti-apoptotic action of 3,5-diCQA was partially dependent on its capacity for anti-oxidation and the suppression of caspase-3 activity. Conclusion: 3,5-diCQA displays anti-oxidative and anti-apoptotic activ-ity in HMEC-1 due to scavenging of intracellular ROS induced by LPS, and the suppression of caspase-3 activity.

  14. Cortical regulation of dopamine depletion-induced dendritic spine loss in striatal medium spiny neurons.

    Science.gov (United States)

    Neely, M D; Schmidt, D E; Deutch, A Y

    2007-10-26

    The proximate cause of Parkinson's disease is striatal dopamine depletion. Although no overt toxicity to striatal neurons has been reported in Parkinson's disease, one of the consequences of striatal dopamine loss is a decrease in the number of dendritic spines on striatal medium spiny neurons (MSNs). Dendrites of these neurons receive cortical glutamatergic inputs onto the dendritic spine head and dopaminergic inputs from the substantia nigra onto the spine neck. This synaptic arrangement suggests that dopamine gates corticostriatal glutamatergic drive onto spines. Using triple organotypic slice cultures composed of ventral mesencephalon, striatum, and cortex of the neonatal rat, we examined the role of the cortex in dopamine depletion-induced dendritic spine loss in MSNs. The striatal dopamine innervation was lesioned by treatment of the cultures with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) or by removing the mesencephalon. Both MPP+ and mesencephalic ablation decreased MSN dendritic spine density. Analysis of spine morphology revealed that thin spines were preferentially lost after dopamine depletion. Removal of the cortex completely prevented dopamine depletion-induced spine loss. These data indicate that the dendritic remodeling of MSNs seen in parkinsonism occurs secondary to increases in corticostriatal glutamatergic drive, and suggest that modulation of cortical activity may be a useful therapeutic strategy in Parkinson's disease.

  15. Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

    Science.gov (United States)

    Roy, Abhro Jyoti; Stanely Mainzen Prince, P

    2013-10-01

    The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats.

  16. Effects of folic acid awareness on knowledge and consumption for the prevention of birth defects among Hispanic women in several U.S. Communities.

    Science.gov (United States)

    Prue, Christine E; Hamner, Heather C; Flores, Alina L

    2010-04-01

    The neural tube defects (NTDs) anencephaly and spina bifida, are serious birth defects of the brain and spine that affect about 3000 pregnancies per year in the United States. Research has found a strong link between periconceptional folic acid consumption and NTD prevention. Because Hispanic women have higher rates of NTD-affected births, targeted folic acid promotion efforts were conducted in several major cities from 1999 to 2002. Efforts included paid and unpaid placements of Spanish language public service announcements (PSAs) and community-level education through the use of promotoras. Analyses focused on whether or not women's reported awareness of folic acid, regardless of promotion type, impacted their knowledge or behavior. Women who reported awareness of folic acid had greater folic acid knowledge and use of vitamins containing folic acid than those not aware. Analyses also examined the use of vitamins containing folic acid by pregnancy intention among women who reported awareness of folic acid. The results were varied. Pregnancy wanters were most likely to use vitamins containing folic acid daily. For this group, however, awareness did not play as large a role in whether they reported consuming a vitamin containing folic acid or not, as it did for pregnancy waiters and avoiders.

  17. Knowledge and use of folic acid for birth defect prevention among women of childbearing age in Shanghai, China: A prospective cross-sectional study

    OpenAIRE

    Liang, Huan; Ma, Duan; Zhou, Shu-Feng; Li, Xiaotian

    2011-01-01

    Summary Background This study aimed to assess the knowledge, attitude, and practice of folic acid intake for prevention of birth defects in Chinese women of child-bearing age. Material/Methods In this prospective cross-sectional study, a total of 1,338 women aged 20?45 years were randomly selected for interview. Data on folic acid knowledge and information on folic acid intake in the subjects were collected. Age, education, contraception, and status of family planning were used as the indepen...

  18. Knowledge and use of folic acid for birth defect prevention among women of childbearing age in Shanghai, China: A prospective cross-sectional study

    OpenAIRE

    Liang, Huan; MA, DUAN; Zhou, Shu-Feng; Li, Xiaotian

    2011-01-01

    Summary Background This study aimed to assess the knowledge, attitude, and practice of folic acid intake for prevention of birth defects in Chinese women of child-bearing age. Material/Methods In this prospective cross-sectional study, a total of 1,338 women aged 20–45 years were randomly selected for interview. Data on folic acid knowledge and information on folic acid intake in the subjects were collected. Age, education, contraception, and status of family planning were used as the indepen...

  19. All-trans retinoic acid prevents epidural fibrosis through NF-κB signaling pathway in post-laminectomy rats.

    Science.gov (United States)

    Zhang, Chao; Kong, Xiaohong; Ning, Guangzhi; Liang, Zhipin; Qu, Tongjun; Chen, Feiran; Cao, Daigui; Wang, Tianyi; Sharma, Hari S; Feng, Shiqing

    2014-04-01

    Laminectomy is a widely accepted treatment for lumbar disorders, and epidural fibrosis (EF) is a common complication. EF is thought to cause post-operative pain recurrence after laminectomy or discectomy. All-trans retinoic acid (ATRA) has shown anti-fibrotic, anti-inflammatory, and anti-proliferative functions. The object of this study was to investigate the effects of ATRA on the prevention of EF in post-laminectomy rats. In vitro, the anti-fibrotic effect of ATRA was demonstrated with cultured fibroblasts count, which comprised of those that were cultured with/without ATRA. In vivo, rats underwent laminectomy at the L1-L2 levels. We first demonstrated the beneficial effects using 0.05% ATRA compared to vehicle (control group). We found that a higher concentration of ATRA (0.1%) achieved dose-dependent results. Hydroxyproline content, Rydell score, vimentin-positive cell density, fibroblast density, inflammatory cell density and inflammatory factor expression levels all suggested better outcomes in the 0.1% ATRA rats compared to the other three groups. Presumably, these effects involved ATRA's ability to suppress transforming growth factor (TGF-β1) and interleukin (IL)-6 which was confirmed with reverse-transcriptase polymerase chain reaction (RT-PCR). Finally we demonstrated that ATRA down-regulated nuclear factor (NF)-κB by immunohistochemistry and western blotting for p65 and inhibition of κB (IκBα), respectively. Our findings indicate that topical application of ATRA can inhibit fibroblast proliferation, decrease TGF-β1 and IL-6 expression level, and prevent epidural scar adhesion in rats. The highest concentration employed in this study (0.1%) was the most effective. ATRA suppressed EF through down-regulating NF-κB signaling, whose specific mechanism is suppression of IκB phosphorylation and proteolytic degradation.

  20. [Prevention of intrauterine adhesion with auto-crosslinked hyaluronic acid gel: a prospective, randomized, controlled clinical study].

    Science.gov (United States)

    Xiao, Songshu; Wan, Yajun; Zou, Fangjun; Ye, Mingzhu; Deng, Henan; Ma, Jiezhi; Wei, Yingying; Tan, Chen; Xue, Min

    2015-01-01

    To evaluate the efficacy and safety of auto-crosslinked hyaluronic acid (HA) gel for preventing intrauterine adhesion (IUA) after hysteroscopic adhesiolysis. A prospective, randomized, double blinded and controlled clinical trial (level I) was performed. According to American Fertility Society (AFS) scoring system, 120 patients (treatment group: 60 cases, control group: 60 cases) with moderate to severe IUA were enrolled. Upon completion of adhesiolysis, a Foley balloon catheter was first introduced into the uterine cavity and then 3 ml of auto-crosslinked HA gel for patients in the treatment group; patients in the control group, however, only received Foley balloon catheter. Second-look hysteroscopic examination was performed to all patients at 3 months postoperatively for evaluation of IUA. Primary endpoint was the reduction rate of IUA at 3 months after surgery. The secondary endpoints include total AFS score, score of each individual AFS category. At 3 months after surgery, auto-crosslinked HA gel resulted in significantly higher effective rate for reduction of adhesion, the effective rate were 76% (42/55) and 48% (27/56) respectively (P = 0.000 9); the total AFS score of treatment group was 2.1 ± 1.1, and significantly lower than that of control group (3.7 ± 2.5, P = 0.000 8). Application of auto-crosslinked HA gel after surgery significantly enhanced the improvement for each individual patient with regard to their adhesive type and menstrual pattern (P = 0.037 8, P = 0.000 4). The treatment group had significantly lower proportion of patients with moderate to severe adhesive stages than that of control group [13% (7/55) versus 38% (21/56), P = 0.000 6]. No adverse events and complications were observed. Auto-crosslinked HA gel coule be able to reduce IUA, decrease adhesion severity, and improve menopause postoperatively. This absorbable auto-crosslinked HA gel is proposed as a barrier for preventing IUA after intrauterine procedures.

  1. In vivo dendrite regeneration after injury is different from dendrite development

    Science.gov (United States)

    Li, Tun; Jan, Lily Yeh; Jan, Yuh Nung

    2016-01-01

    Neurons receive information along dendrites and send signals along axons to synaptic contacts. The factors that control axon regeneration have been examined in many systems, but dendrite regeneration has been largely unexplored. Here we report that, in intact Drosophila larvae, a discrete injury that removes all dendrites induces robust dendritic growth that recreates many features of uninjured dendrites, including the number of dendrite branches that regenerate and responsiveness to sensory stimuli. However, the growth and patterning of injury-induced dendrites is significantly different from uninjured dendrites. We found that regenerated arbors cover much less territory than uninjured neurons, fail to avoid crossing over other branches from the same neuron, respond less strongly to mechanical stimuli, and are pruned precociously. Finally, silencing the electrical activity of the neurons specifically blocks injury-induced, but not developmental, dendrite growth. By elucidating the essential features of dendrites grown in response to acute injury, our work builds a framework for exploring dendrite regeneration in physiological and pathological conditions. PMID:27542831

  2. trans-10,cis-12 conjugated linoleic acid prevents adiposity but not insulin resistance induced by an atherogenic diet in hamsters.

    Science.gov (United States)

    Simón, Edurne; Macarulla, M Teresa; Churruca, Itziar; Fernández-Quintela, Alfredo; Portillo, María P

    2006-02-01

    While conjugated linoleic acid (CLA) has received a great deal of attention as a supplement that can favourably modify body composition, its potential impact on insulin sensitivity has not received equal attention. The aim of the present work was to analyse the effects of trans-10,cis-12 CLA isomer on insulin sensitivity in hamsters fed an atherogenic diet. Hamsters were divided into three groups: one group was fed a chow diet (control) and the other two a semipurified atherogenic diet supplemented with 0.5% linoleic acid (LA) or trans-10,cis-12 CLA, respectively. Serum glucose, FFAs, insulin, leptin and adiponectin were measured using commercial kits. HOMA-IR was calculated using the formula of Matthews et al. PPARgamma mRNA was assessed in epididymal adipose tissue by reverse transcription-polymerase chain reaction (RT-PCR). After 6 weeks, atherogenic feeding produced an increase in body fat accumulation as compared with control feeding. The addition of trans-10,cis-12 CLA to the atherogenic diet avoided this feature. Atherogenic feeding also led to significantly higher serum concentrations of glucose, insulin, FFAs, as well as greater HOMA-IR values. trans-10,cis-12 CLA did not prevent these effects. No significant differences were found among experimental groups in serum leptin and adiponectin concentrations, nor in PPARgamma expression. In summary, although the addition of trans-10,cis-12 CLA to an atherogenic diet reduces fat accumulation, it does not improve the impairment of insulin action associated with this feeding. The maintenance of insulin resistance in hamsters fed the atherogenic CLA-enriched diet is probably due to the high serum FFA concentration observed in these animals.

  3. Bile acid binding resin prevents fat accumulation through intestinal microbiota in high-fat diet-induced obesity in mice.

    Science.gov (United States)

    Kusumoto, Yukie; Irie, Junichiro; Iwabu, Kaho; Tagawa, Hirotsune; Itoh, Arata; Kato, Mari; Kobayashi, Nana; Tanaka, Kumiko; Kikuchi, Rieko; Fujita, Masataka; Nakajima, Yuya; Morimoto, Kohkichi; Sugizaki, Taichi; Yamada, Satoru; Kawai, Toshihide; Watanabe, Mitsuhiro; Oike, Yuichi; Itoh, Hiroshi

    2017-06-01

    Bile acid binding resin (BAR) absorbs intestinal bile acids, and improves obesity and metabolic disorders, but the precise mechanism remains to be clarified. Recent findings reveal that obesity is associated with skewed intestinal microbiota. Thus, we investigated the effect of BAR on intestinal microbiota and the role of microbiota in the prevention of obesity in high-fat diet-induced obesity in mice. Male Balb/c mice were fed a low-fat diet (LFD), high-fat diet (HFD), or HFD with BAR (HFD+BAR), and then metabolic parameters, caecal microbiota, and metabolites were investigated. The same interventions were conducted in germ-free and antibiotic-treated mice. The frequency of Clostridium leptum subgroup was higher in both HFD-fed and HFD+BAR-fed mice than in LFD-fed mice. The frequency of Bacteroides-Prevotella group was lower in HFD-fed mice than in LFD-fed mice, but the frequency was higher in HFD+BAR-fed mice than in HFD-fed mice. Caecal propionate was lower in HFD-fed mice than in LFD-fed mice, and higher in HFD+BAR-fed mice than in HFD-fed mice. HFD+BAR-fed mice showed lower adiposity than HFD-fed mice, and the reduction was not observed in germ-free or antibiotic-treated mice. Colonized germ-free mice showed a reduction in adiposity by BAR administration. Energy expenditure was lower in HFD-fed mice and higher in HFD+BAR-fed mice, but the increments induced by administration of BAR were not observed in antibiotic-treated mice. Modulation of intestinal microbiota by BAR could be a novel therapeutic approach for obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Recrystallization phenomena of solution grown paraffin dendrites

    NARCIS (Netherlands)

    Hollander, F.F.A.; Stasse, O.; Suchtelen, van J.; Enckevort, van W.J.P.

    2001-01-01

    Paraffin crystals were grown from decane solutions using a micro-Bridgman set up for in-situ observation of the morphology at the growth front. It is shown that for large imposed velocities, dendrites are obtained. After dendritic growth, aging or recrystallization processes set in rather quickly, c

  5. A Case of Plasmacytoid Dendritic Cell Leukemia

    Directory of Open Access Journals (Sweden)

    Köpeczi Judit Beáta

    2013-04-01

    Full Text Available Introduction: Plasmacytoid dendritic cell leukemia is a rare subtype of acute leukemia, which has recently been established as a distinct pathologic entity that typically follows a highly aggressive clinical course in adults. The aim of this report is to present a case of plasmacytoid dendritic cell leukemia due to its rarity and difficulty to recognize and diagnose it.

  6. Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid : community-based randomized clinical trial in Italy and the Netherlands

    NARCIS (Netherlands)

    Bortolus, Renata; Blom, Fenneke; Filippini, Francesca; van Poppel, Mireille N. M.; Leoncini, Emanuele; de Smit, Denhard J.; Benetollo, Pier Paolo; Cornel, Martina C.; de Walle, Hermien E. K.; Mastroiacovo, Pierpaolo

    2014-01-01

    Background: In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first-and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital

  7. Potential mechanisms explaining why hydrolyzed casein-based diets outclass single amino acid-based diets in the prevention of autoimmune diabetes in diabetes-prone BB rats

    NARCIS (Netherlands)

    Visser, J. T. J.; Bos, N. A.; Harthoorn, L. F.; Stellaard, F.; Beijer-Liefers, S.; Rozing, J.; van Tol, E. A. F.

    2012-01-01

    Background It remains controversial whether avoidance of dietary diabetogenic triggers, such as cow's milk proteins, can prevent type 1 diabetes in genetically susceptible individuals. Here, different extensive casein hydrolysates (HC) and single amino acid (AA) formulations were tested for their ef

  8. Salvianolic Acid B Prevents Bone Loss in Prednisone-Treated Rats through Stimulation of Osteogenesis and Bone Marrow Angiogenesis

    Science.gov (United States)

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S. S.; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10−6 mol/L to 10−7 mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  9. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis.

    Directory of Open Access Journals (Sweden)

    Liao Cui

    Full Text Available Glucocorticoid (GC induced osteoporosis (GIO is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1 In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2 In vitro study: In concentration from 10(-6 mol/L to 10(-7 mol/L, Sal B stimulated bone marrow stromal cell (MSC differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin m

  10. Early events in axon/dendrite polarization.

    Science.gov (United States)

    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.

  11. Numerical simulation of facet dendrite growth

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhi; CHEN Chang-le; HAO Li-mei

    2008-01-01

    Numerical simulation based on phase field method was performed to describe the solidification of silicon. The effect of anisotropy, undercooling and coupling parameter on dendrite growth shape was investigated. It is indicated that the entire facet dendrite shapes are obtained by using regularized phase field model. Steady state tip velocity of dendrite drives to a fixed value when γ≤0.13. With further increasing the anisotropy value, steady state tip velocity decreases and the size is smaller. With the increase in the undercooling and coupling parameter, crystal grows from facet to facet dendrite. In addition, with increasing coupling parameter, the facet part of facet dendrite decreases gradually, which is in good agreement with Wulff theory.

  12. Omega-3 fatty acids regulate NLRP3 inflammasome activation and prevent behavior deficits after traumatic brain injury.

    Science.gov (United States)

    Lin, Chao; Chao, Honglu; Li, Zheng; Xu, Xiupeng; Liu, Yinlong; Bao, Zhongyuan; Hou, Lijun; Liu, Yan; Wang, Xiaoming; You, Yongping; Liu, Ning; Ji, Jing

    2017-04-01

    Omega-3 fatty acids (ω-3 FAs) attenuate inflammation and improve neurological outcome in response to traumatic brain injury (TBI), but the specific anti-inflammatory mechanisms remain to be elucidated. Here we found that NLRP3 inflammasome and subsequent pro-inflammatory cytokines were activated in human brains after TBI. Rats treated with ω-3 FAs had significantly less TBI-induced caspase-1 cleavage and IL-1β secretion than those with vehicle. G protein-coupled receptor 40 (GPR40) was observed to be involved in this anti-inflammation. GW1100, a GPR40 inhibitor, eliminated the anti-inflammatory effect of ω-3 FAs after TBI. β-Arrestin-2 (ARRB2), a downstream scaffold protein of GPR40, was activated to inhibit inflammation via directly binding with NLRP3 in the ω-3 FAs treatment group. Interestingly, we also observed that ω-3 FAs prevented NLRP3 mitochondrial localization, which was reversed by GW1100. Furthermore, ω-3 FAs markedly ameliorated neuronal death and behavioral deficits after TBI, while GW1100 significantly suppressed this effect. Collectively, these data indicate that the GPR40-mediated pathway is involved in the inhibitory effects of ω-3 FAs on TBI-induced inflammation and ARRB2 is activated to interact with NLRP3.

  13. Application of hyaluronic acid/sodium alginate-based microparticles to prevent tissue adhesion in a rabbit model.

    Science.gov (United States)

    Back, Ja Hoon; Cho, Wan Jin; Kim, Jun Ho; Park, Il Kyu; Kwon, Sung Won

    2016-04-01

    Postsurgical adhesion formation is a concern in every field of surgery. We evaluated the efficacy of hyaluronic acid/sodium alginate-based microparticle anti-adhesive agents (MP) for the prevention of postsurgical adhesion formation in a standardized rabbit model. To evaluate the anti-adhesion effect, a uterus-abdominal wall abrasion model was created in rabbits. On the surface of the injured uterus, an anti-adhesive agent, Interceed(®) or MP, was applied (positive control and study groups, respectively; n = 10 each). In another group of 10 animals, neither agent was applied (negative control group). The adhesion levels were graded 3 weeks after surgery. Acute and chronic toxicity was also evaluated. The grade of adhesion was significantly lower in the MP group than in the negative control and positive control groups. No evidence of acute or chronic toxicity induced by this material was found in blood and tissue analysis. MP shows potential as an effective novel type of resorbable biomaterial to reduce postoperative adhesion. The easy placement and handling of this material make the MP powder attractive as a tissue adhesion barrier.

  14. A study on the prevention of salmonella infection by using the aggregation characteristics of lactic Acid bacteria.

    Science.gov (United States)

    Kim, Min-Soo; Yoon, Yeo-Sang; Seo, Jae-Gu; Lee, Hyun-Gi; Chung, Myung-Jun; Yum, Do-Young

    2013-06-01

    Salmonella is one of the major pathogenic bacteria that cause food poisoning. This study investigated whether heat-killed as well as live Lactobacillus protects host animal against Salmonella infection. Live and heat-killed Lactobacillusacidophilus was administered orally to Sprague-Dawley rats for 2 weeks before the rats were inoculated with Salmonella. Rise in body temperature was moderate in the group that was treated with heat-killed bacteria as compared to the Salmonella control group. The mean amount of feed intake and water consumption of each rat in the heat-killed bacteria group were nearly normal. The number of fecal Salmonellae was comparable between the live and the heat-killed L. acidophilus groups. This finding shows that L. acidophilus facilitates the excretion of Salmonella. Moreover, the levels of pro inflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta, in the heat-killed L. acidophilus group were significantly lower when compared to the levels in the Salmonella control group. These results indicate that nonviable lactic acid bacteria also could play an important role in preventing infections by enteric pathogens such as Salmonella.

  15. Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice

    Directory of Open Access Journals (Sweden)

    Jyuhn-Huarng Juang

    2014-01-01

    Full Text Available It has been shown that all-trans retinoid acid (ATRA hinders the development of autoimmune diabetes by inducing immune tolerance status. Meanwhile, exendin-4 increases beta-cell function and mass. Thus, we hypothesized that ATRA and exendin-4 combination therapy would prevent and reverse autoimmune diabetes. NOD/scid mice were intravenously transferred with splenocytes isolated from 12-week-old female NOD mice. After adoptive transfer, mice were treated with vehicle, ATRA (0.5 mg/mouse intraperitoneally every other day, exendin-4 (3 μg/kg subcutaneously twice daily, or combination for 6 weeks. Compared with vehicle, ATRA (P=0.022 and ATRA plus exendin-4 (P=0.013 treatment delayed the onset of diabetes. The pancreatic insulin content in mice treated with ATRA (P=0.013 and exendin-4 (P<0.02 was significantly higher than that of control mice. All but one spontaneous diabetic NOD mouse treated with ATRA and/or exendin-4 remained persistent hyperglycemic. ATRA and/or exendin-4 treatment did not alter their blood glucose levels and survival. Our results indicate that, before the onset of autoimmune diabetes, ATRA and exendin-4 treatment alone preserves pancreatic beta cells; ATRA and ATRA plus exendin-4 treatment delays the onset of autoimmune diabetes. However, after the onset of autoimmune diabetes, ATRA and/or exendin-4 treatment is unable to reverse hyperglycemia or improve survival.

  16. Moderate water stress prevents the postharvest decline of ascorbic acid in spinach (Spinacia oleracea L.) but not in spinach beet (Beta vulgaris L.).

    Science.gov (United States)

    Mogren, Lars M; Beacham, Andrew M; Reade, John P H; Monaghan, James M

    2016-07-01

    Babyleaf salads such as spinach (Spinacia oleracea L.) and spinach beet (Beta vulgaris L. subsp. cicla var. cicla) are an important dietary source of antioxidants such as ascorbic acid (vitamin C). Such compounds may be important in disease prevention in consumers but the level of these compounds in leaves frequently declines after harvest. As such, methods to maintain antioxidant levels in fresh produce are being sought. Irrigation deficits were used to apply water stress to S. oleracea and B. vulgaris plants. This treatment prevented postharvest decline of leaf ascorbic acid content in S. oleracea but not in B. vulgaris. Ascorbic acid levels in leaves at harvest were unaffected by the treatment in both species compared to well-watered controls. We have shown that restricted irrigation provides a viable means to maintain leaf vitamin content after harvest in S. oleracea, an important finding for producers, retailers and consumers alike. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  17. Self-antigen presentation by dendritic cells in autoimmunity

    Directory of Open Access Journals (Sweden)

    Ann-Katrin eHopp

    2014-02-01

    Full Text Available The operation of both central and peripheral tolerance ensures the prevention of autoimmune diseases. The maintenance of peripheral tolerance requires self-antigen presentation by professional antigen presenting cells (APCs. Dendritic cells (DCs are considered as major APCs involved in this process. The current review discusses the role of DCs in autoimmune diseases, the various factors involved in the induction and maintenance of tolerogenic DC phenotype and pinpoints their therapeutic capacity as well as potential novel targets for future clinical studies.

  18. Dendritic Cells in the Cancer Microenvironment

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    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.

  19. Iso-α-acids, Bitter Components of Beer, Prevent Inflammation and Cognitive Decline Induced in a Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Ano, Yasuhisa; Dohata, Atsushi; Taniguchi, Yoshimasa; Hoshi, Ayaka; Uchida, Kazuyuki; Takashima, Akihiko; Nakayama, Hiroyuki

    2017-03-03

    Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long, healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor γ. In normal mice, oral administration of iso-α-acids led to a significant increase both in CD11b and CD206 double-positive anti-inflammatory type microglia (p iso-α-acids resulted in a 21% reduction in amyloid β in the cerebral cortex as observed by immunohistochemical analysis, a significant reduction in inflammatory cytokines such as IL-1β and chemokines including macrophage inflammatory protein-1α in the cerebral cortex (p iso-α-acid-fed mice were due to the induction of microglia to an anti-inflammatory phenotype. The present study is the first to report that amyloid β deposition and inflammation are suppressed in a mouse model of Alzheimer's disease by a single component, iso-α-acids, via the regulation of microglial activation. The suppression of neuroinflammation and improvement in cognitive function suggests that iso-α-acids contained in beer may be useful for the prevention of dementia.

  20. Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity

    Science.gov (United States)

    Ryu, Yuhee; Jin, Li; Kee, Hae Jin; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Lin, Ming Quan; Jeong, Myung Ho

    2016-01-01

    Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway. PMID:27703224

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

    Institute of Scientific and Technical Information of China (English)

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

    2000-01-01

    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 fullthickness 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<0.01), and reached the lowest point,0.63mL/L ± 0.20mL/L, 10.81mmol/L ±2.58mmol/L and 2.23 mmol/h ± 0.73mmol/h respectively, at the 12th h postburn. Although restored to some degree 24 h after thermal injury, the variables above were still statistically lower, compared with those of control animals at the 48th h postburn. The GMBF and EC were also significantly reduced after severe burns, consistent with the trend of gastric acid production changes.CONCLUSION Gastric acid production, as well as GMBF and EC was predominantly decreased in the early postburn stage, suggesting that gastric mucosal ischemia and hypoxia with resultant disturbance in energy metabolism, but not gastric acid proper, might be the decisive factor in the pathogenesis of AGML after thermal injury, and that the preventive use of 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.

  2. Triggering of dendritic cell apoptosis by xanthohumol.

    Science.gov (United States)

    Xuan, Nguyen Thi; Shumilina, Ekaterina; Gulbins, Erich; Gu, Shuchen; Götz, Friedrich; Lang, Florian

    2010-07-01

    Xanthohumol, a flavonoid from beer with anticancer activity is known to trigger apoptosis in a variety of tumor cells. Xanthohumol further has anti-inflammatory activity. However, little is known about the effect of xanthohumol on survival and function of immune cells. The present study thus addressed the effect of xanthohumol on dendritic cells (DCs), key players in the regulation of innate and adaptive immunity. To this end, mouse bone marrow-derived DCs were treated with xanthohumol with subsequent assessment of enzymatic activity of acid sphingomyelinase (Asm), ceramide formation determined with anti-ceramide antibodies in FACS and immunohistochemical analysis, caspase activity utilizing FITC conjugated anti-active caspase 8 or caspase 3 antibodies in FACS and by Western blotting, DNA fragmentation by determining the percentage of cells in the sub-G1 phase and cell membrane scrambling by annexin V binding in FACS analysis. As a result, xanthohumol stimulated Asm, enhanced ceramide formation, activated caspases 8 and 3, triggered DNA fragmentation and led to cell membrane scrambling, all effects virtually absent in DCs from gene targeted mice lacking functional Asm or in wild-type cells treated with sphingomyelinase inhibitor amitriptyline. In conclusion, xanthohumol stimulated Asm leading to caspase activation and apoptosis of bone marrow-derived DCs.

  3. Downregulation of transient K+ channels in dendrites of hippocampal CA1 pyramidal neurons by activation of PKA and PKC.

    Science.gov (United States)

    Hoffman, D A; Johnston, D

    1998-05-15

    We have reported recently a high density of transient A-type K+ channels located in the distal dendrites of CA1 hippocampal pyramidal neurons and shown that these channels shape EPSPs, limit the back-propagation of action potentials, and prevent dendritic action potential initiation (). Because of the importance of these channels in dendritic signal propagation, their modulation by protein kinases would be of significant interest. We investigated the effects of activators of cAMP-dependent protein kinase (PKA) and the Ca2+-dependent phospholipid-sensitive protein kinase (PKC) on K+ channels in cell-attached patches from the distal dendrites of hippocampal CA1 pyramidal neurons. Inclusion of the membrane-permeant PKA activators 8-bromo-cAMP (8-br-cAMP) or forskolin in the dendritic patch pipette resulted in a depolarizing shift in the activation curve for the transient channels of approximately 15 mV. Activation of PKC by either of two phorbol esters also resulted in a 15 mV depolarizing shift of the activation curve. Neither PKA nor PKC activation affected the sustained or slowly inactivating component of the total outward current. This downregulation of transient K+ channels in the distal dendrites may be responsible for some of the frequently reported increases in cell excitability found after PKA and PKC activation. In support of this hypothesis, we found that activation of either PKA or PKC significantly increased the amplitude of back-propagating action potentials in distal dendrites.

  4. The Receptor Tyrosine Kinase Mertk Regulates Dendritic Cell Production of BAFF

    OpenAIRE

    Gohlke, P.R.; Williams, J. C.; Vilen, B J; Dillon, S.R.; Tisch, R; Matsushima, G.K.

    2009-01-01

    The MerTK receptor tyrosine kinase is an important negative regulator of dendritic cell function and is required to prevent B cell autoimmunity in vivo. It is not currently known however, if any causal relationship exists between these two aspects of MerTK function. We sought to determine if dendritic cells from mice lacking MerTK (mertk−/− mice) have characteristics that may aid in the development of B cell autoimmunity. Specifically, we found that mertk−/− mice contain an elevated number of...

  5. Dendritic potassium channels in hippocampal pyramidal neurons.

    Science.gov (United States)

    Johnston, D; Hoffman, D A; Magee, J C; Poolos, N P; Watanabe, S; Colbert, C M; Migliore, M

    2000-05-15

    Potassium channels located in the dendrites of hippocampal CA1 pyramidal neurons control the shape and amplitude of back-propagating action potentials, the amplitude of excitatory postsynaptic potentials and dendritic excitability. Non-uniform gradients in the distribution of potassium channels in the dendrites make the dendritic electrical properties markedly different from those found in the soma. For example, the influence of a fast, calcium-dependent potassium current on action potential repolarization is progressively reduced in the first 150 micrometer of the apical dendrites, so that action potentials recorded farther than 200 micrometer from the soma have no fast after-hyperpolarization and are wider than those in the soma. The peak amplitude of back-propagating action potentials is also progressively reduced in the dendrites because of the increasing density of a transient potassium channel with distance from the soma. The activation of this channel can be reduced by the activity of a number of protein kinases as well as by prior depolarization. The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A-type K+ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and the action potentials occur within the appropriate time window. This time window could be in the order of 15 ms and may play a role in long-term potentiation induced by pairing EPSPs and back-propagating action potentials.

  6. Non-linear dendrites can tune neurons

    Directory of Open Access Journals (Sweden)

    Romain Daniel Cazé

    2014-03-01

    Full Text Available A signature of visual, auditory, and motor cortices is the presence of neurons tuned to distinct features of the environment. While neuronal tuning can be observed in most brain areas, its origin remains enigmatic, and new calcium imaging data complicate this problem. Dendritic calcium signals, in a L2/3 neuron from the mouse visual cortex, display a wide range of tunings that could be different from the neuronal tuning (Jia et al 2010. To elucidate this observation we use multi-compartmental models of increasing complexity, from a binary to a realistic biophysical model of L2/3 neuron. These models possess non-linear dendritic subunits inside which the result of multiple excitatory inputs is smaller than their arithmetic sum. While dendritic non-linear subunits are ad-hoc in the binary model, non-linearities in the realistic model come from the passive saturation of synaptic currents. Because of these non-linearities our neuron models are scatter sensitive: the somatic membrane voltage is higher when presynaptic inputs target different dendrites than when they target a single dendrite. This spatial bias in synaptic integration is, in our models, the origin of neuronal tuning. Indeed, assemblies of presynaptic inputs encode the stimulus property through an increase in correlation or activity, and only the assembly that encodes the preferred stimulus targets different dendrites. Assemblies coding for the non-preferred stimuli target single dendrites, explaining the wide range of observed tunings and the possible difference between dendritic and somatic tuning. We thus propose, in accordance with the latest experimental observations, that non-linear integration in dendrites can generate neuronal tuning independently of the coding regime.

  7. Preventive effects of omega-3 and omega-6 Fatty acids on peroxide mediated oxidative stress responses in primary human trabecular meshwork cells.

    Directory of Open Access Journals (Sweden)

    Theofilos Tourtas

    Full Text Available Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H₂O₂, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H₂O₂ further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H₂O₂ stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H₂O₂ mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H₂O₂ induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side

  8. 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.

    Science.gov (United States)

    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.

  9. Dendritic tellurides acting as antioxidants

    Institute of Scientific and Technical Information of China (English)

    XU Huaping; WANG Yapei; WANG Zhiqiang; LIU Junqiu; Mario Smet; Wim Dehaen

    2006-01-01

    We have described the synthesis of a series of poly(aryl ether) dendrimers with telluride in the core and oligo(ethylene oxide) chains at the periphery which act as glutathione peroxidase (GPx) mimics. These series of compounds were well characterized by 1H-NMR, 13C-NMR and ESI-MS. Using different ROOH (H2O2, cumene hydroperoxide) for testing the antioxidizing properties of these compounds, we have found that from generation 0 to 2, the activity of the dendritic GPx mimics first decreased and then increased. This can be explained on the basis of a greater steric hindrance, going from generation 0 to 1, and stronger binding interactions going from generation 1 to 2. In other words, there exists a balance between binding interactions and steric hindrance that may optimize the GPx activity.

  10. Fate mapping of dendritic cells

    Directory of Open Access Journals (Sweden)

    Barbara Ursula Schraml

    2015-05-01

    Full Text Available Dendritic cells (DCs are a heterogeneous group of mononuclear phagocytes with versatile roles in immunity. They are classified predominantly based on phenotypic and functional properties, namely their stellate morphology, expression of the integrin CD11c and major histocompatibility class II molecules, as well as their superior capacity to migrate to secondary lymphoid organs and stimulate naïve T cells. However, these attributes are not exclusive to DCs and often change within inflammatory or infectious environments. This led to debates over cell identification and questioned even the mere existence of DCs as distinct leukocyte lineage. Here, we review experimental approaches taken to fate map DCs and discuss how these have shaped our understanding of DC ontogeny and lineage affiliation. Considering the ontogenetic properties of DCs will help to overcome the inherent shortcomings of purely phenotypic- and function-based approaches to cell definition and will yield a more robust way of DC classification.

  11. Dendritic Cells for Anomaly Detection

    CERN Document Server

    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.

  12. Prevention of pancreatic fistula using polyethylene glycolic acid mesh reinforcement around pancreatojejunostomy: the propensity score-matched analysis.

    Science.gov (United States)

    Kang, Jae Seung; Han, Youngmin; Kim, Hongbeom; Kwon, Wooil; Kim, Sun-Whe; Jang, Jin-Young

    2017-03-01

    Several small-scale studies have shown that wrapping polyethylene glycolic acid (PGA) mesh around the anastomotic site reinforced pancreaticojejunostomy following pancreatoduodenectomy (PD) with favorable outcomes. This study investigated the efficacy of PGA mesh for reducing postoperative pancreatic fistula (POPF) and evaluated other risk factors for POPF. This study enrolled 464 consecutive patients who underwent PD performed by one surgeon between 2006 and 2015, including a PGA group of 281 patients (60.6%) and a control group of 183 patients (39.4%). All pancreatico-enteric anastomoses were performed using double-layered, duct-to-mucosa, end-to-side pancreaticojejunostomy. Mean patient age was 63.1 years. The rates of overall (27.0% vs. 37.2%, P = 0.024) and clinically relevant (Grades B, C; 13.9% vs. 24.0%, P = 0.006) POPF were significantly lower in the PGA than in the control group. Following propensity score matching, the rates of clinically relevant POPF (12.6% vs. 22.4%, P = 0.024) and complications (40.2% vs. 63.8%, P < 0.001) remained significantly lower in the PGA group. Multivariate analysis showed that non-pancreatic disease, greater blood loss, higher body mass index, and non-application of PGA mesh were significantly associated with the development of clinically relevant POPF. PGA mesh reinforcement of pancreaticojejunostomy may prevent POPF as well as reducing overall abdominal complications after PD. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  13. Salvianolic acid B functioned as a competitive inhibitor of matrix metalloproteinase-9 and efficiently prevented cardiac remodeling

    Science.gov (United States)

    2010-01-01

    Background Infarct-induced left ventricular (LV) remodeling is a deleterious consequence after acute myocardial infarction (MI) which may further advance to congestive heart failure. Therefore, new therapeutic strategies to attenuate the effects of LV remodeling are urgently needed. Salvianolic acid B (SalB) from Salviae mitiorrhizae, which has been widely used in China for the treatment of cardiovascular diseases, is a potential candidate for therapeutic intervention of LV remodeling targeting matrix metalloproteinase-9 (MMP-9). Results Molecular modeling and LIGPLOT analysis revealed in silico docking of SalB at the catalytic site of MMP-9. Following this lead, we expressed truncated MMP-9 which contains only the catalytic domain, and used this active protein for in-gel gelatin zymography, enzymatic analysis, and SalB binding by Biacore. Data generated from these assays indicated that SalB functioned as a competitive inhibitor of MMP-9. In our rat model for cardiac remodeling, western blot, echocardiography, hemodynamic measurement and histopathological detection were used to detect the effects and mechanism of SalB on cardio-protection. Our results showed that in MI rat, SalB selectively inhibited MMP-9 activities without affecting MMP-9 expression while no effect of SalB was seen on MMP-2. Moreover, SalB treatment in MI rat could efficiently increase left ventricle wall thickness, improve heart contractility, and decrease heart fibrosis. Conclusions As a competitive inhibitor of MMP-9, SalB presents significant effects on preventing LV structural damage and preserving cardiac function. Further studies to develop SalB and its analogues for their potential for cardioprotection in clinic are warranted. PMID:20735854

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

    Science.gov (United States)

    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.

  15. Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin.

    Science.gov (United States)

    White, James; Guerin, Theresa; Swanson, Hollie; Post, Steven; Zhu, Haining; Gong, Ming; Liu, Jun; Everson, William V; Li, Xiang-An; Graf, Gregory A; Ballard, Hubert O; Ross, Stuart A; Smart, Eric J

    2008-01-01

    In the current study, we examined whether diabetes affected the ability of HDL to stimulate nitric oxide (NO) production. Using HDL isolated from both diabetic humans and diabetic mouse models, we found that female HDL no longer induced NO synthesis, despite containing equivalent amounts of estrogen as nondiabetic controls. Furthermore, HDL isolated from diabetic females and males prevented acetylcholine-induced stimulation of NO generation. Analyses of both the human and mouse diabetic HDL particles showed that the HDLs contained increased levels of myristic acid. To determine whether myristic acid associated with HDL particles was responsible for the decrease in NO generation, myristic acid was added to HDL isolated from nondiabetic humans and mice. Myristic acid-associated HDL inhibited the generation of NO in a dose-dependent manner. Importantly, diabetic HDL did not alter the levels of endothelial NO synthase or acetylcholine receptors associated with the cells. Surprisingly, diabetic HDL inhibited ionomycin-induced stimulation of NO production without affecting ionomycin-induced increases in intracellular calcium. Further analysis indicated that diabetic HDL prevented calmodulin from interacting with endothelial NO synthase (eNOS) but did not affect the activation of calmodulin kinase or calcium-independent mechanisms for stimulating eNOS. These studies are the first to show that a specific fatty acid associated with HDL inhibits the stimulation of NO generation. These findings have important implications regarding cardiovascular disease in diabetic patients.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  18. A delta-catenin signaling pathway leading to dendritic protrusions.

    Science.gov (United States)

    Abu-Elneel, Kawther; Ochiishi, Tomoyo; Medina, Miguel; Remedi, Monica; Gastaldi, Laura; Caceres, Alfredo; Kosik, Kenneth S

    2008-11-21

    Delta-catenin is a synaptic adherens junction protein pivotally positioned to serve as a signaling sensor and integrator. Expression of delta-catenin induces filopodia-like protrusions in neurons. Here we show that the small GTPases of the Rho family act coordinately as downstream effectors of delta-catenin. A dominant negative Rac prevented delta-catenin-induced protrusions, and Cdc42 activity was dramatically increased by delta-catenin expression. A kinase dead LIMK (LIM kinase) and a mutant Cofilin also prevented delta-catenin-induced protrusions. To link the effects of delta-catenin to a physiological pathway, we noted that (S)-3,5-dihydroxyphenylglycine (DHPG) activation of metabotropic glutamate receptors induced dendritic protrusions that are very similar to those induced by delta-catenin. Furthermore, delta-catenin RNA-mediated interference can block the induction of dendritic protrusions by DHPG. Interestingly, DHPG dissociated PSD-95 and N-cadherin from the delta-catenin complex, increased the association of delta-catenin with Cortactin, and induced the phosphorylation of delta-catenin within the sites that bind to these protein partners.

  19. The influence of mechanochemical modification on prevention of toxic ability of humic acids towards phenanthrene in aquatic environment

    Science.gov (United States)

    Shekhovtsova, N. S.; Maltseva, E. V.; Glyzina, T. S.; Ovchinnikova, I. S.

    2015-11-01

    The aim of the research work is to quantify interaction between phenanthrene with modified humic acids in aquatic environment. The changes in the structure and properties of humic acids after modifications were studied with 1H NMR spectroscopy and potentiometric titration methods. Our research demonstrates that the application of thiourea as a modified agent increases the binding capacity of humic acids towards phenanthrene.

  20. The dietary fatty acids of patients with coronary artery disease and controls in Curacao - Implications for primary and secondary prevention

    NARCIS (Netherlands)

    Brouwer, DAJ; vanderDijs, FPL; Leerink, CB; Steward, HN; Kroon, TAJ; Suverkropp, GHJ; Romer, JWP; vanDoormaal, JJ; Muskiet, FAJ

    1997-01-01

    Patients with coronary artery disease are advised to augment their dietary linoleic acid intakes at the expense of saturated fatty acids. We investigated whether the dietary linoleic acid intake of 57 patients with coronary artery disease (47 males, 10 females; ages 61 +/- 10 years) in Curacao is hi

  1. Dendritic development of hippocampal CA1 pyramidal cells in a neonatal hypoxia-ischemia injury model.

    Science.gov (United States)

    Zhao, Yan Dong; Ou, Shan; Cheng, Sai Yu; Xiao, Zhi; He, Wen Juan; Zhang, Jin Hai; Ruan, Huai Zhen

    2013-09-01

    It is believed that neonatal hypoxia-ischemia (HI) brain injury causes neuron loss and brain functional defects. However, the effect of HI brain injury on dendritic development of the remaining pyramidal cells of the hippocampus and the reaction of contralateral hippocampal neurons require further studies. The Morris water maze and Golgi-Cox staining were used to evaluate the learning and memory and dendritic morphology of pyramidal cells. The results of Golgi-Cox staining showed CA1 pyramidal neurons of HI injury models with fewer bifurcations and shorter dendrite length than the naive control group. The density of dendritic spines of hippocampal CA1 pyramidal neurons was significantly lower in the HI brain injury group than in controls. With respect to hippocampal function, the HI brain injury group presented cognitive deficits in the reference memory task and probe trail. In the HI group, the pyramidal cells of left hippocampus that did not experienced ischemia but did experience hypoxia had more complex dendrites and higher density of spine than the HI injury side and control. The functional implementation of injured hippocampus might depend mainly on the hypertrophy of contralateral hippocampus after HI brain injury. Corticosterone can partially prevent the hippocampal pyramidal cells from HI injury and reduce the difference of the bilateral hippocampus pyramidal cells, but there was no improvement in learning and memory.

  2. Making Li-metal electrodes rechargeable by controlling the dendrite growth direction

    Science.gov (United States)

    Liu, Yadong; Liu, Qi; Xin, Le; Liu, Yuzi; Yang, Fan; Stach, Eric A.; Xie, Jian

    2017-07-01

    The long-standing issue of Li-dendrite formation and growth during repeated plating or stripping processes prevents the practical application of Li-metal anodes for high-specific-energy batteries. Here we develop an approach to control dendrite growth by coating the separator with functionalized nanocarbon (FNC) with immobilized Li ions. During cycling, the Li dendrites grow toward each other simultaneously from both the FNC layer on the separator and the Li-metal anode; when the dendrites meet, the growth changes direction: rather than penetrating the separator, a dense Li layer is formed between the separator and the Li anode. This controlled growth alleviates the solid electrolyte interphase formation, reduces the decomposition of the electrolyte, and improves the cyclability of the Li-metal cell. In a Li/LiFePO4 coin cell with three different electrolytes, we show that this approach enables a long stable cycle life (>800 cycles with 80% retention of the initial capacity) and improved efficiency (>97%). Our method offers promise for application in practical Li-metal batteries, and it may also be useful for tackling dendrite issues for other metals.

  3. Dendritic cells are stressed out in tumor.

    Science.gov (United States)

    Maj, Tomasz; Zou, Weiping

    2015-09-01

    A recently paper published in Cell reports that dendritic cells (DCs) are dysfunctional in the tumor environment. Tumor impairs DC function through induction of endoplasmic reticulum stress response and subsequent disruption of lipid metabolic homeostasis.

  4. Dendritic ion channelopathy in acquired epilepsy

    Science.gov (United States)

    Poolos, Nicholas P.; Johnston, Daniel

    2012-01-01

    Summary Ion channel dysfunction or “channelopathy” is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Here we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. PMID:23216577

  5. Dendritic ion channelopathy in acquired epilepsy.

    Science.gov (United States)

    Poolos, Nicholas P; Johnston, Daniel

    2012-12-01

    Ion channel dysfunction or "channelopathy" is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Herein we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  6. Artificial Dendritic Cells: Multi-faceted Perspectives

    CERN Document Server

    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...

  7. “Dermal dendritic cells” comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages

    OpenAIRE

    Ochoa,Maria Teresa; Loncaric, Anya; Krutzik, Stephan R.; Becker, Todd C.; Modlin, Robert L.

    2008-01-01

    A key cell type of the resident skin immune system is the dendritic cell, which in normal skin is located in two distinct microanatomical compartments: Langerhans cells (LC) mainly in the epidermis and dermal dendritic cells (DDC) in the dermis. Here, the lineage of dermal dendritic cells was investigated using monoclonal antibodies and immunohistology. We provide evidence that “dermal dendritic cells” comprise at least two major phenotypic populations of dendritic appearing cells: immature D...

  8. Diazotization of kynurenine by acidified nitrite secreted from indoleamine 2,3-dioxygenase-expressing myeloid dendritic cells.

    Science.gov (United States)

    Hara, Toshiaki; Yamakura, Fumiyuki; Takikawa, Osamu; Hiramatsu, Rie; Kawabe, Tsutomu; Isobe, Ken-Ichi; Nagase, Fumihiko

    2008-03-20

    Indoleamine 2,3-dioxygenase (IDO)-initiated tryptophan metabolism along the kynurenine (Kyn) pathway regulates T-cell responses in some dendritic cells (DC) such as plasmacytoid DC. A Kyn assay using HPLC showed that samples were frequently deproteinized with trichloroacetic acid (TCA). In the present study, bone marrow-derived myeloid DC (BMDC) were differentiated from mouse bone marrow cells with GM-CSF. CpG oligodeoxynucleotides (CpG) induced the expression of IDO protein with NO production in BMDC cultured for 24 h. The concentrations of Kyn in the culture supernatants were not increased by stimulation with CpG but rather decreased by based on the Kyn assay after deproteinization with TCA. The level of Kyn exogenously added into the cell-free culture supernatant of BMDC stimulated with CpG was severely decreased by deproteinization with TCA but not methanol, and the decrease was prevented when BMDC was stimulated with CpG in the presence of a NOS inhibitor. Under acidic conditions, Kyn reacted with nitrite produced by BMDC, and generated a new compound that was not detected by Ehrlich reagent reacting with the aromatic amino residue of Kyn. An analysis by mass spectrometry showed the new compound to be a diazotization form of Kyn. In conclusion, the deproteinization of samples by acidic treatment should be avoided for the Kyn assay when NO is produced.

  9. The dendritic spines of interneurons are dynamic structures influenced by PSA-NCAM expression.

    Science.gov (United States)

    Guirado, Ramon; Perez-Rando, Marta; Sanchez-Matarredona, David; Castillo-Gómez, Esther; Liberia, Teresa; Rovira-Esteban, Laura; Varea, Emilio; Crespo, Carlos; Blasco-Ibáñez, José Miguel; Nacher, Juan

    2014-11-01

    Excitatory neurons undergo dendritic spine remodeling in response to different stimuli. However, there is scarce information about this type of plasticity in interneurons. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is a good candidate to mediate this plasticity as it participates in neuronal remodeling and is expressed by some mature cortical interneurons, which have reduced dendritic arborization, spine density, and synaptic input. To study the connectivity of the dendritic spines of interneurons and the influence of PSA-NCAM on their dynamics, we have analyzed these structures in a subpopulation of fluorescent spiny interneurons in the hippocampus of glutamic acid decarboxylase-enhanced green fluorescent protein transgenic mice. Our results show that these spines receive excitatory synapses. The depletion of PSA in vivo using the enzyme Endo-Neuraminidase-N (Endo-N) increases spine density when analyzed 2 days after, but decreases it 7 days after. The dendritic spine turnover was also analyzed in real time using organotypic hippocampal cultures: 24 h after the addition of EndoN, we observed an increase in the apparition rate of spines. These results indicate that dendritic spines are important structures in the control of the synaptic input of hippocampal interneurons and suggest that PSA-NCAM is relevant in the regulation of their morphology and connectivity.

  10. Early and Persistent Dendritic Hypertrophy in the Basolateral Amygdala following Experimental Diffuse Traumatic Brain Injury.

    Science.gov (United States)

    Hoffman, Ann N; Paode, Pooja R; May, Hazel G; Ortiz, J Bryce; Kemmou, Salma; Lifshitz, Jonathan; Conrad, Cheryl D; Currier Thomas, Theresa

    2017-01-01

    In the pathophysiology of traumatic brain injury (TBI), the amygdala remains understudied, despite involvement in processing emotional and stressful stimuli associated with anxiety disorders, such as post-traumatic stress disorder (PTSD). Because the basolateral amygdala (BLA) integrates inputs from sensory and other limbic structures coordinating emotional learning and memory, injury-induced changes in circuitry may contribute to psychiatric sequelae of TBI. This study quantified temporal changes in dendritic complexity of BLA neurons after experimental diffuse TBI, modeled by midline fluid percussion injury. At post-injury days (PIDs) 1, 7, and 28, brain tissue from sham and brain-injured adult, male rats was processed for Golgi, glial fibrillary acidic protein (GFAP), or silver stain and analyzed to quantify BLA dendritic branch intersections, activated astrocytes, and regional neuropathology, respectively. Compared to sham, brain-injured rats at all PIDs showed enhanced dendritic branch intersections in both pyramidal and stellate BLA neuronal types, as evidenced by Sholl analysis. GFAP staining in the BLA was significantly increased at PID1 and 7 in comparison to sham. However, the BLA was relatively spared from neuropathology, demonstrated by an absence of argyrophilic accumulation over time, in contrast to other brain regions. These data suggest an early and persistent enhancement of dendritic complexity within the BLA after a single diffuse TBI. Increased dendritic complexity would alter information processing into and through the amygdala, contributing to emotional symptoms post-TBI, including PTSD.

  11. Free energy and dendritic self-organisation

    Directory of Open Access Journals (Sweden)

    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.

  12. Synaptic Control of Secretory Trafficking in Dendrites

    Directory of Open Access Journals (Sweden)

    Cyril Hanus

    2014-06-01

    Full Text Available Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca2+/calmodulin-dependent protein kinases (CaMK. Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.

  13. A cost minimisation analysis of olive oil versus hyperoxygenated fatty acid treatment for the prevention of pressure ulcers in primary health care: A randomised controlled trial.

    Science.gov (United States)

    Lupiañez-Pérez, Inmaculada; Morilla-Herrera, Juan Carlos; Kaknani-Uttumchanchandani, Shakira; Lupiañez-Perez, Yolanda; Cuevas-Fernandez-Gallego, Magdalena; Martin-Santos, Francisco; Caro-Bautista, Jorge; Morales-Asencio, Jose Miguel

    2017-09-18

    Pressure ulcers represent a major current health problem and cause an important economic impact on the health care system. Most studies on the prevention of pressure ulcers have been carried out in hospital contexts, with respect to the use of hyperoxygenated fatty acids, and to date no studies have specifically examined the use of olive oil-based treatments. To evaluate the cost of using extra virgin olive oil, rather than hyperoxygenated fatty acids, in the prevention of pressure ulcers among persons with impaired mobility and receiving home care. Cost minimisation analysis of the results obtained from a non-inferiority, triple-blind, parallel, multicentre, randomised clinical trial. Population attending primary health care centres in Andalusia (Spain). 831 immobilised patients at risk of suffering pressure ulcers. These persons were included in the study and randomly assigned as follows: 437 to the olive oil group and 394 to the hyperoxygenated fatty acid group. At the end of the follow-up period, the results obtained by the olive oil group were not inferior to those of the hyperoxygenated fatty acid group, and did not exceed the 10% delta limit. The total treatment cost for 16 weeks was €19,758 with hyperoxygenated fatty acids and €9,566 with olive oil. Overall, the olive oil treatment was €10,192 less costly. It has been concluded the non-inferiority of olive oil makes this product an effective alternative for the prevention of pressure ulcers in patients who are immobilised and in a domestic environment. This treatment enables considerable savings in direct costs. This article is protected by copyright. All rights reserved. © 2017 by the Wound Healing Society.

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

    Energy Technology Data Exchange (ETDEWEB)

    Flores, Claudia [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Degoutin, Stephanie [Univ. Lille, 59000 Lille (France); UMET, Ingénierie des Systèmes Polymères, Université de Lille 1, 59655 Villeneuve d' Ascq (France); Chai, Feng [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Raoul, Gwenael [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Service Chirurgie Maxillo-Faciale, CHRU de Lille, 59000 Lille (France); Hornez, Jean-Chritophe [Laboratoire des Matériaux Céramiques et Procédés Associés (LMCPA), Université de Valenciennes, 59300 Valenciennes (France); Martel, Bernard [Univ. Lille, 59000 Lille (France); UMET, Ingénierie des Systèmes Polymères, Université de Lille 1, 59655 Villeneuve d' Ascq (France); Siepmann, Juergen [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Ferri, Joel [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Service Chirurgie Maxillo-Faciale, CHRU de Lille, 59000 Lille (France); Blanchemain, Nicolas, E-mail: nicolas.blanchemain@univ-lille2.fr [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France)

    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 60 μm, allowing for incorporation inside the macropores (100 μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25–30 days 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. - Highlights: • The optimization of microparticle preparation parameters allows to obtain a size compatible with the bone substitute porosity • PDL% has a direct impact on the burst effect, a control release of gentamicin was obtained • The incorporation of microparticles into the

  15. In Situ Observation of Cell-to-Dendrite Transition

    Institute of Scientific and Technical Information of China (English)

    PAN Xiu-Hong; HONG Yong; JIN Wei-Qing

    2005-01-01

    @@ The cell-to-dendrite transition of succinonitrile melt suspended on a loop-shaped Pt heater is observed in real time by a differential interference microscope coupled with Schlieren technique. The transition is divided into two parts: a dendrite coalition process and a subsequent dendrite elimination process. Firstly the dendrites from the same cell are united into a single dendrite. Secondly the competitive growth of dendrites from different cells leads to the elimination of dendrites. The two processes can be understood when involving crystallographic orientation. In addition, the tip velocity and primary spacing of a cell/dendrite are also measured. It turns out that the primary spacing has a significant jump, whereas the growth velocity has no abrupt change during the cell-to-dendrite transition.

  16. Dendritic cells in melanoma - immunohistochemical study and research trends.

    Science.gov (United States)

    Nedelcu, Roxana Ioana; Ion, Daniela Adriana; Holeab, Cosmin Adrian; Cioplea, Mirela Daniela; Brînzea, Alice; Zurac, Sabina Andrada

    2015-01-01

    Cutaneous dendritic cells play multiple physiological roles and are involved in various pathophysiological processes. Research studies of dendritic cells abound in the medical literature. Nevertheless, the role of dendritic cells in melanoma regression phenomenon is not completely understood. We conducted a scientometric analysis in order to highlight the current state on research regarding dendritic cells and melanoma. We also performed an immunohistochemical study, using specific markers for dendritic cells (CD1a, langerin). We evaluated the frequency and distribution of dendritic cells in areas of tumor regression compared to the areas of inflammatory infiltrate of melanoma without regression. The immunohistochemical study we performed revealed that dendritic cells are more frequent in the regressed areas, comparing with non-regressed ones. In regressed areas, dendritic cells have a predominant nodular pattern (19 cases), followed by diffuse isolate pattern (eight cases) and mixed pattern (diffuse and nodular) (three cases). In melanoma without regression, most cases presented a diffuse pattern (27 cases) of dendritic cells distribution. In conclusion, our immunohistochemical study stressed differences between frequency and distribution of dendritic cells located in the melanoma with regression and melanoma without regression. These data suggest that dendritic cells are involved in the regression phenomenon. Following the literature analysis we obtained, we observed that dendritic cells profile in melanoma with regression was poorly studied. Insights into antitumor immune response and dendritic cells may be essential for the understanding of the potential prognostic role of dendritic cells in melanoma and for the development of new promising therapeutic strategies for melanoma.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction

    Directory of Open Access Journals (Sweden)

    Junghyun Kim

    2016-09-01

    Full Text Available Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE against damage to retinal vascular cells were investigated in streptozotocin (STZ-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-κB and inducible nitric oxide synthase (iNOS were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-κB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-κB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells.

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

    Directory of Open Access Journals (Sweden)

    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

  20. Intravenous 1 gram tranexamic acid for prevention of blood loss and blood transfusion during caesarean section: a randomized case control study

    Directory of Open Access Journals (Sweden)

    Babita Ramani

    2014-04-01

    Full Text Available Background: Aim of current study was to determine the effect of tranexamic acid in reducing blood loss during and after C-section. Methods: All women undergoing LSCS were divided in two groups viz study and control group. All were requested for pre-op and post-op Hb%, PCV and TRBC. Intravenous tranexamic acid one gm was given to study group (not to control group 10 min prior to skin incision and blood loss in both groups was calculated by weighing prewieghed pads soaked in blood. Results: Post-op blood loss was significantly lower in study group (P = 0.020. Hb% changes in post-op period is significant in control group (P = 0.037. Conclusions: Tranexamic acid is safe and effective in preventing post-partum hemorrhage after caesarean section. [Int J Reprod Contracept Obstet Gynecol 2014; 3(2.000: 366-369

  1. Architecture of apical dendrites in the murine neocortex: dual apical dendritic systems.

    Science.gov (United States)

    Escobar, M I; Pimienta, H; Caviness, V S; Jacobson, M; Crandall, J E; Kosik, K S

    1986-04-01

    A monoclonal antibody (5F9) against microtubule-associated protein 2 is a selective and sensitive marker for neocortical dendrites in the mouse. The marker stains all dendrites. It affords a particularly comprehensive picture of the patterns of arrangements of apical dendrites which are most intensely stained with this antibody. Dual systems of apical dendrites arise from the polymorphic neurons of layer VI, on the one hand, and the pyramidal neurons of layers II-V, on the other. Terminal arborization of the former is concentrated principally at the interface of layers V and IV, while that of the latter is in the molecular layer. Apical dendrites of both systems are grouped into fascicles. In supragranular layers and in upper layer VI-lower layer V, where apical dendrites are most abundant, the fascicles coalesce into septa. These generate a honeycomb-like pattern, subdividing these cortical levels into columnar spaces of approximately 20-40 micron diameter. At the level of layer IV, where the number of apical dendrites is greatly reduced, the fascicles are isolated bundles. These bundles have the form of circular, elliptical or rectangular columns in the primary somatosensory, temporal and frontal regions, respectively. Those in the barrel field are preferentially concentrated in the sides of barrels and the interbarrel septa. The configurations of the dendritic fascicles, particularly the midcortical bundles, may conform to the spatial configuration of investing axons of interneurons.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Long chain fatty acid acylated derivatives of quercetin-3-o-glucoside as antioxidants to prevent lipid oxidation.

    Science.gov (United States)

    Warnakulasuriya, Sumudu N; Ziaullah; Rupasinghe, H P Vasantha

    2014-11-06

    Flavonoids have shown promise as natural plant-based antioxidants for protecting lipids from oxidation. It was hypothesized that their applications in lipophilic food systems can be further enhanced by esterification of flavonoids with fatty acids. Quercetin-3-O-glucoside (Q3G) was esterified individually with six selected long chain fatty acids: stearic acid (STA), oleic acid (OLA), linoleic acid (LNA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA), using Candida antarctica B lipase as the biocatalyst. The antioxidant activity of esterified flavonoids was evaluated using lipid oxidation model systems of poly-unsaturated fatty acids-rich fish oil and human low density lipoprotein (LDL), in vitro. In the oil-in-water emulsion, Q3G esters exhibited 50% to 100% inhibition in primary oxidation and 30% to 75% inhibition in secondary oxidation. In bulk oil, Q3G esters did not provide considerable protection from lipid oxidation; however, Q3G demonstrated more than 50% inhibition in primary oxidation. EPA, DHA and ALA esters of Q3G showed significantly higher inhibition in Cu2+- and peroxyl radical-induced LDL oxidation in comparison to Q3G.

  4. Long Chain Fatty Acid Acylated Derivatives of Quercetin-3-O-Glucoside as Antioxidants to Prevent Lipid Oxidation

    Directory of Open Access Journals (Sweden)

    Sumudu N. Warnakulasuriya

    2014-11-01

    Full Text Available Flavonoids have shown promise as natural plant-based antioxidants for protecting lipids from oxidation. It was hypothesized that their applications in lipophilic food systems can be further enhanced by esterification of flavonoids with fatty acids. Quercetin-3-O-glucoside (Q3G was esterified individually with six selected long chain fatty acids: stearic acid (STA, oleic acid (OLA, linoleic acid (LNA, α-linolenic acid (ALA, eicosapentaenoic acid (EPA and decosahexaenoic acid (DHA, using Candida antarctica B lipase as the biocatalyst. The antioxidant activity of esterified flavonoids was evaluated using lipid oxidation model systems of poly-unsaturated fatty acids-rich fish oil and human low density lipoprotein (LDL, in vitro. In the oil-in-water emulsion, Q3G esters exhibited 50% to 100% inhibition in primary oxidation and 30% to 75% inhibition in secondary oxidation. In bulk oil, Q3G esters did not provide considerable protection from lipid oxidation; however, Q3G demonstrated more than 50% inhibition in primary oxidation. EPA, DHA and ALA esters of Q3G showed significantly higher inhibition in Cu2+- and peroxyl radical-induced LDL oxidation in comparison to Q3G.

  5. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies.

    Science.gov (United States)

    Wilson, R Douglas; Johnson, Jo-Ann; Wyatt, Philip; Allen, Victoria; Gagnon, Alain; Langlois, Sylvie; Blight, Claire; Audibert, François; Désilets, Valerie; Brock, Jo-Ann; Koren, Gideon; Goh, Y Ingrid; Goh, Ingrid; Nguyen, Patricia; Kapur, Bhushan

    2007-12-01

    To provide information regarding the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies, so that physicians, midwives, nurses, and other health care workers can assist in the education of women in the pre-conception phase of their health care. OPTION: Supplementation with folic acid and vitamins is problematic, since 50% of pregnancies are unplanned, and women's health status may not be optimal when they conceive. Folic acid in combination with a multivitamin supplement has been associated with a decrease in specific birth defects. Medline, PubMed, and Cochrane Database were searched for relevant English language articles published between 1985 and 2007. The previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of November 1993 and statements from the American College of Obstetrics and Gynecology and Canadian College of Medical Geneticists were also reviewed in developing this clinical practice guideline. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Promoting the use of folic acid and a multivitamin supplement among women of reproductive age will reduce the incidence of birth defects. The costs are those of daily vitamin supplementation and eating a healthy diet. 1. Women in the reproductive age group should be advised about the benefits of folic acid in addition to a multivitamin supplement during wellness visits (birth control renewal, Pap testing, yearly examination) especially if pregnancy is contemplated. (III-A) 2. Women should be advised to maintain a healthy diet, as recommended in Eating Well With Canada's Food Guide (Health Canada). Foods containing excellent to good sources of folic acid are fortified grains, spinach, lentils, chick peas, asparagus, broccoli, peas, Brussels sprouts, corn, and oranges. However, it is unlikely that diet alone can provide

  6. Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

    Science.gov (United States)

    Wood, Gwendolyn E.; Young, L. Trevor; Reagan, Lawrence P.; Chen, Biao; McEwen, Bruce S.

    2004-03-01

    Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Targeting vaccines to dendritic cells.

    Science.gov (United States)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-03-01

    Dendritic cells (DC) are specialized antigen presenting cells (APC) with a remarkable ability to take up antigens and stimulate major histocompatibility complex (MHC)-restricted specific immune responses. Recent discoveries have shown that their role in initiating primary immune responses seems to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC are considered to play a central role for the provocation of primary immune responses by vaccination. A rational way of improving the potency and safety of new and already existing vaccines could therefore be to direct vaccines specifically to DC. There is a need for developing multifunctional vaccine drug delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC.

  9. Plasmacytoid dendritic cells in antiviral immunity and autoimmunity

    Institute of Scientific and Technical Information of China (English)

    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.

  10. Potential for dietary ω-3 fatty acids to prevent nonalcoholic fatty liver disease and reduce the risk of primary liver cancer.

    Science.gov (United States)

    Jump, Donald B; Depner, Christopher M; Tripathy, Sasmita; Lytle, Kelli A

    2015-11-01

    Nonalcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity, and its prevalence is anticipated to increase as the obesity epidemic remains unabated. NAFLD is now the most common cause of chronic liver disease in developed countries and is defined as excessive lipid accumulation in the liver, that is, hepatosteatosis. NAFLD ranges in severity from benign fatty liver to nonalcoholic steatohepatitis (NASH), and NASH is characterized by hepatic injury, inflammation, oxidative stress, and fibrosis. NASH can progress to cirrhosis, and cirrhosis is a risk factor for primary hepatocellular carcinoma (HCC). The prevention of NASH will lower the risk of cirrhosis and NASH-associated HCC. Our studies have focused on NASH prevention. We developed a model of NASH by using mice with the LDL cholesterol receptor gene ablated fed the Western diet (WD). The WD induces a NASH phenotype in these mice that is similar to that seen in humans and includes robust induction of hepatic steatosis, inflammation, oxidative stress, and fibrosis. With the use of transcriptomic, lipidomic, and metabolomic approaches, we examined the capacity of 2 dietary ω-3 (n-3) polyunsaturated fatty acids, eicosapentaenoic acid (20:5ω-3; EPA) and docosahexaenoic acid (22:6ω-3; DHA), to prevent WD-induced NASH. Dietary DHA was superior to EPA at attenuating WD-induced changes in plasma lipids and hepatic injury and at reversing WD effects on hepatic metabolism, oxidative stress, and fibrosis. The outcome of these studies suggests that DHA may be useful in preventing NASH and reducing the risk of HCC. © 2015 American Society for Nutrition.

  11. Dendritic poly(L-lysine)-b-Poly(L-lactide)-b-dendritic poly(L-lysine) amphiphilic gene delivery vectors: roles of PLL dendritic generation and enhanced transgene efficacies via termini modification.

    Science.gov (United States)

    Li, Yang; Zhu, Yingdan; Xia, Kejia; Sheng, Ruilong; Jia, Lin; Hou, Xiaodong; Xu, Yuhong; Cao, Amin

    2009-08-10

    As an effort to prepare new efficient gene delivery vectors, we have recently developed and reported an amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine) D(2)-PLLA-D(2) with two-generation PLL dendrons and a PLLA block. In this work, we continued to explore the roles of dendritic PLL generation in DNA binding and intracellular delivery of gene, and a new series of amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine)s D(n)-PLLA-D(n) (n = 3-5) were synthesized and were structurally characterized. Furthermore, plasmid DNA binding affinity for these cationic amphiphiles was examined by agarose gel electrophoresis and fluorescence titration assay in pure water and PBS buffer solution containing 150 mM NaCl (pH = 7.4), respectively. By dynamic light scattering (DLS) and transmission electronic microscopy (TEM), the interaction and complexation in between were investigated, concerning the DNA/vector polyplex particle morphologies and zeta potentials. Utilizing a human hepatocellular carcinoma cell-line SMMC-7721, cell toxicity, and gene transfection in vitro were explored. To further improve transgene efficiency for these synthetic cationic amphiphiles as gene delivery vectors, new structural DE(n)-PLLA-DE(n) (n = 2-3) were prepared through an amino termini modification of the D(n)-PLLA-D(n) (n = 2-3) with less toxic 4,7,10,13-tetraazatridecanoic acids, and gene transfection with these DE(n)-PLLA-DE(n) (n = 2-3) was examined with an alternative human gastric carcinoma cell-line HGC-27. As a result, the high plasmid DNA binding affinity, low cytotoxicity, and much enhanced transgene efficacy suggest a new possible clue to design effective synthetic gene delivery vectors with amphiphilic skeleton and less toxic polyamine building blocks.

  12. The peroxisomal enzyme L-PBE is required to prevent the dietary toxicity of medium-chain fatty acids.

    Science.gov (United States)

    Ding, Jun; Loizides-Mangold, Ursula; Rando, Gianpaolo; Zoete, Vincent; Michielin, Olivier; Reddy, Janardan K; Wahli, Walter; Riezman, Howard; Thorens, Bernard

    2013-10-17

    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. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Mitochondria-dependent apoptosis of con A-activated T lymphocytes induced by asiatic acid for preventing murine fulminant hepatitis.

    Science.gov (United States)

    Guo, Wenjie; Liu, Wen; Hong, Shaocheng; Liu, Hailiang; Qian, Cheng; Shen, Yan; Wu, Xuefeng; Sun, Yang; Xu, Qiang

    2012-01-01

    Selectively facilitating apoptosis of activated T cells is essential for the clearance of pathogenic injurious cells and subsequent efficient resolution of inflammation. However, few chemicals have been reported to trigger apoptosis of activated T cells for the treatment of hepatitis without affecting quiescent T cells. In the present study, we found that asiatic acid, a natural triterpenoid, selectively triggered apoptosis of concanavalin A (Con A)-activated T cells in a mitochondria-dependent manner indicated by the disruption of the mitochondrial transmembrane potential, release of cytochrome c from mitochondria to cytosol, caspases activation, and cleavage of PARP. In addition, asiatic acid also induced the cleavage of caspase 8 and Bid and augmented Fas expression in Con A-activated T cells. However, following activation of T cells from MRL(lpr/lpr) mice with mutation of Fas demonstrated a similar susceptibility to asiatic acid-induced apoptosis compared with normal T cells, suggesting that Fas-mediated death-receptor apoptotic pathway does not mainly contribute to asiatic acid-induced cell death. Furthermore, asiatic acid significantly alleviated Con A-induced T cell-dependent fulminant hepatitis in mice, as assessed by reduced serum transaminases, pro-inflammatory cytokines, and pathologic parameters. Consistent with the in vitro results, asiatic acid also induced apoptosis of activated CD4(+) T cells in vivo. Taken together, our results demonstrated that the ability of asiatic acid to induce apoptosis of activated T cells and its potential use in the treatment of T-cell-mediated inflammatory diseases.

  15. Nerve Conduction Through Dendrites via Proton Hopping.

    Science.gov (United States)

    Kier, Lemont B

    2017-01-01

    In our previous studies of nerve conduction conducted by proton hopping, we have considered the axon, soma, synapse and the nodes of Ranvier. The role of proton hopping described the passage of information through each of these units of a typical nerve system. The synapse projects information from the axon to the dendrite and their associated spines. We have invoked the passage of protons via a hopping mechanism to illustrate the continuum of the impulse through the system, via the soma following the dendrites. This is proposed to be a continuum invoked by the proton hopping method. With the proposal of the activity through the dendrites, via proton hopping, a complete model of the nerve function is invoked. At each step to the way, a water pathway is present and is invoked in the proposed model as the carrier of the message via proton hopping. The importance of the dendrites is evident by the presence of a vast number of spines, each possessing the possibility to carry unique messages through the nervous system. With this model of the role of dendrites, functioning with the presence of proton hopping, a complete model of the nerve system is presented. The validity of this model will be available for further studies and models to assess it's validity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Redefining the role of dendritic cells in periodontics.

    Science.gov (United States)

    Venkatesan, Gomathinayagam; Uppoor, Ashita; Naik, Dilip G

    2013-11-01

    A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells (DCs) are required to explain how this remarkable system is energized and directed. DCs consist of a family of antigen presenting cells, which are bone-marrow-derived cells that patrol all tissues of the body with the possible exceptions of the brain and testes. DCs function to capture bacteria and other pathogens for processing and presentation to T cells in the secondary lymphoid organs. They serve as an essential link between innate and adaptive immune systems and induce both primary and secondary immune responses. As a result of progress worldwide, there is now evidence of a central role for dendritic cells in initiating antigen-specific immunity and tolerance. This review addresses the origins and migration of DCs to target sites, their basic biology and plasticity in playing a key role in periodontal diseases, and finally, selected strategies being pursued to harness its ability to prevent periodontal diseases.

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

    Energy Technology Data Exchange (ETDEWEB)

    Gautama, R.S.; Kusuma, G.J.; Lestari, I.; Anggana, R.P. [Bandung Inst. Teknologi (Indonesia). Dept. of Mining Engineering, Faculty of Mining and Petroleum Engineering

    2010-07-01

    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.

  18. A hyaluronic acid-based compound inhibits fibroblast senescence induced by oxidative stress in vitro and prevents oral mucositis in vivo.

    Science.gov (United States)

    Cirillo, Nicola; Vicidomini, Antonio; McCullough, Michael; Gambardella, Antonio; Hassona, Yazan; Prime, Stephen S; Colella, Giuseppe

    2015-07-01

    Virtually all patients receiving radio- and chemotherapy for cancer develop oral mucositis, a severe and highly debilitating condition. The onset of mucositis is thought to involve the production of reactive oxygen species (ROS) in the submucosa. Here we investigated a possible protective effect of a commercial formulation of hyaluronic acid (HA) enriched with amino acids (Mucosamin(®)) against the damage induced by oxidative stress both in vitro and in vivo. Transient exposure of normal human oral fibroblasts to hydrogen peroxide (H(2)O(2)) led to irreversible senescence, as demonstrated by sustained increase in the levels of p16(INK4A) and SA-βGal. Conditioned media from senescent fibroblasts induced detrimental effects on keratinocytes, as shown by reduced metabolic activity and migration capability. Pre-treatment with Mucosamin(®) prevented H(2)O(2) -induced, but not TGF-β-induced, fibroblast senescence with a concomitant reduction of fibroblast-induced loss of keratinocyte vitality and functional activity. Finally, data from a case-series of patients undergoing radio/chemotherapy strongly suggested that prophylactic use of the hyaluronic acid-based compound in the form of a spray may be effective in preventing the onset of oral mucositis.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Colominic acid inhibits the proliferation of cultured bovine aortic endothelial cells and injures their monolayers: cell density-dependent effects prevented by sulfation.

    Science.gov (United States)

    Yamamoto, Chika; Morita, Yuki; Yamaguchi, Shinya; Hayashi, Toshimitsu; Kaji, Toshiyuki

    2006-01-18

    Colominic acid (CA), produced by Escherichia coli K1, is a polymer of sialic acid linked through alpha (2-->8) glycosidic linkages. Although there are several studies on the biological activities of chemically sulfated CA, the activity of CA has been incompletely understood. In the present study, we investigated the effects of CA, prepared as an alpha2,8-linked homopolymer of N-acetylneuraminic acid, on the proliferation and monolayer maintenance of bovine aortic endothelial cells in culture. The results indicate that CA potently inhibits the proliferation of sparse endothelial cells without nonspecific cell damage. The inhibitory effect of CA was markedly stronger than those of sodium spirulan and calcium spirulan, known polysaccharides that inhibit endothelial cell proliferation. On the other hand, in dense endothelial cells, CA induced nonspecific cell damage and markedly injured the monolayer. These results indicate that CA has two distinct effects on vascular endothelial cells: one is the inhibition of proliferation when the cell density is low, and the other is the nonspecific cytotoxicity when the cell density is high. Interestingly, these cell density-dependent effects of CA could be prevented by sulfation of the CA chains. Therefore, it is concluded that CA not only inhibits the proliferation of sparse endothelial cells without nonspecific cell damage but also injures dense cells in a monolayer by nonspecific cytotoxicity, which can be prevented by sulfation of the polysaccharide.

  1. Folic acid supplementation prevents the changes in hepatic promoter methylation status and gene expression in intrauterine growth-retarded piglets during early weaning period.

    Science.gov (United States)

    Jing-Bo, L; Ying, Y; Bing, Y; Xiang-Bing, M; Zhi-Qing, H; Guo-Quan, H; Hong, C; Dai-Wen, C

    2013-10-01

    During intrauterine life, genome interacts with maternal signals to influence the mRNA expression levels of specific genes persistently by regulating DNA methylation status. The objective of this study was to examine the responses of glucocorticoid receptor (GR), peroxisome proliferator-activated receptor alpha and gamma (PPARα and PPARγ) promoter methylation, mRNA expression of genes involved in energy metabolism and metabolite concentrations of intrauterine growth-retarded (IUGR) piglets to dietary folic acid supplementation. According to a 2 × 2 factorial arrangement, 16 IUGR and 16 normal birth weight (NBW) piglets were fed a basal diet or a basal diet supplemented with 5 mg/kg of folic acid from weaning (day 14) to day 35 of age. Triglycerides in hepatic tissue and plasma were significantly elevated in control diets-fed IUGR piglets compared with NBW piglets but were decreased by dietary folic acid supplementation. Hepatic mRNA expression levels of GR, PPARα, PPARγ, fatty acid synthase and phosphoenolpyruvate carboxykinase (PEPCK) in IUGR piglets fed a control diet were significantly higher than that in NBW piglets, and promoter methylation status of GR, PPARα and PPARγ in IUGR piglets was reduced significantly compared with NBW piglets. However, the changes in gene expression and DNA methylation status of IUGR piglets were reversed by dietary folic acid supplementation. Hepatic DNA methyltransferase activity was greater with dietary folic acid supplementation regardless of birth weight. Taken together, these results demonstrated that folic acid supplementation during early period of life could prevent the changes of promoter methylation status and gene expressions in the liver of IUGR piglets.

  2. Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice.

    Science.gov (United States)

    de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2015-03-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Ascorbic Acid

    Science.gov (United States)

    Ascorbic acid is used to prevent and treat scurvy, a disease caused by a lack of vitamin C in ... Ascorbic acid comes in extended-release (long-acting) capsules and tablets, lozenges, syrup, chewable tablets, and liquid drops to ...

  5. Glycyrrhizic acid prevents enteritis through reduction of NF‑κB p65 and p38MAPK expression in rat.

    Science.gov (United States)

    Wang, Yi-Ming; Du, Guo-Qiang

    2016-04-01

    Glycyrrhizic acid has a variety of biological properties, including a protective function in the liver, and anti‑inflammatory, anti‑ulcer, anti‑anaphylaxis, anti‑oxidant, immunoregulatory, antiviral and anticancer activities. The efficacy of glycyrrhizic acid can be increased when combined with other medicines. In the present study, the potential protective effects of glycyrrhizic acid against enteritis in rats, and its role in regulating anti‑inflammation, anti‑oxidation, angiogenic and apoptotic mechanisms were investigated using enzyme‑linked immunosorbent and bicinchoninic acid assays, and reverse transcription‑quantitative polymerase chain reaction and western blotting analyses. Adult male Sprague‑Dawley rats were injected with 20 mg/kg methotrexate (MTX) to establish enteritis. Additionally, rats with MTX‑induced enteritis were peritoneally injected with 200 mg glycyrrhizic acid for 9 weeks. The current study demonstrated that glycyrrhizic acid could alleviate MTX‑induced increases of tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 levels, and raise IL‑10 levels, in rats with enteritis. Treatment with glycyrrhizic acid significantly reduced D‑lactate and intercellular adhesion molecule‑1 gene expression (Penteritis. Pretreatment with glycyrrhizic acid significantly suppressed the promotion of p38 mitogen‑activated protein kinase (p38MAPK), nuclear factor‑κB p65 (NF‑κB p65) protein expression, interferon‑γ protein concentration, and caspase‑3 and cycloxygenase‑2 activity in MTX‑induced enteritis (Penteritis by reducing NF‑κB p65 and p38MAPK expression levels, which may inform future therapeutic strategies for the treatment of enteritis.

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

    Science.gov (United States)

    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. |

  7. Caffeic acid phenethyl ester prevents apoptotic cell death in the developing rat brain after pentylenetetrazole-induced status epilepticus.

    Science.gov (United States)

    Yiş, Uluç; Topçu, Yasemin; Özbal, Seda; Tuğyan, Kazım; Bayram, Erhan; Karakaya, Pakize; Yilmaz, Osman; Kurul, Semra Hız

    2013-11-01

    Population-based studies suggest that seizure incidence is highest during the first year of life, and early-life seizures frequently result in the development of epilepsy and behavioral alterations later in life. The early-life insults like status epilepticus often lead to epileptogenesis, a process in which initial brain injury triggers cascades of molecular, cellular, and network changes and eventually spontaneous seizures. Caffeic acid phenethyl ester is an active component of propolis obtained from honeybees and has neuroprotective properties. The aim of this study was to investigate whether caffeic acid phenethyl ester exerts neuroprotective effects on the developing rat brain after status epilepticus. Twenty-one dams reared Wistar male rats, and 21-day-old rats were divided into three groups: control group, pentylenetetrazole-induced status epilepticus group, and caffeic acid phenethyl ester-treated group. Status epilepticus was induced on the first day of experiment. Caffeic acid phenethyl ester injections (30 mg/kg intraperitoneally) started 40 min after the tonic phase of status epilepticus was reached, and the injections of caffeic acid phenethyl ester were repeated over 5 days. Rats were sacrificed, and brain tissues were collected on the 5th day of experiment after the last injection of caffeic acid phenethyl ester. Apoptotic cell death was evaluated. Histopathological examination showed that caffeic acid phenethyl ester significantly preserved the number of neurons in the CA1, CA3, and dentate gyrus regions of the hippocampus and the prefrontal cortex. It also diminished apoptosis in the hippocampus and the prefrontal cortex. In conclusion, this experimental study suggests that caffeic acid phenethyl ester administration may be neuroprotective in status epilepticus in the developing rat brain.

  8. Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis-associated colorectal cancer acting on Notch signaling and gut microbiota

    NARCIS (Netherlands)

    Piazzi, G.; Argenio, D' G.; Prossomariti, A.; Lembo, V.; Mazzone, G.; Candela, M.; Biagi, E.; Brigidi, P.; Vitaglione, P.; Fogliano, V.; Angelo and others, D' L.

    2014-01-01

    Inflammatory bowel diseases are associated with increased risk of developing colitis-associated colorectal cancer (CAC). Epidemiological data show that the consumption of ¿-3 polyunsaturated fatty acids (¿-3 PUFAs) decreases the risk of sporadic colorectal cancer (CRC). Importantly, recent data have

  9. Detecting Danger: The Dendritic Cell Algorithm

    CERN Document Server

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Directory of Open Access Journals (Sweden)

    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. Nutrient-dependent increased dendritic arborization of somatosensory neurons.

    Science.gov (United States)

    Watanabe, Kaori; Furumizo, Yuki; Usui, Tadao; Hattori, Yukako; Uemura, Tadashi

    2017-01-01

    Suboptimal nutrition imposes developmental constraints on infant animals, which marshal adaptive responses to eventually become mature adults. Such responses are mounted at multiple levels from systemic to cellular. At the cellular level, the underlying mechanisms of cell proliferation control have been intensively studied. However, less is known about how growth of postmitotic and morphologically complex cells, such as neurons, is controlled by nutritional status. We address this question using Class I and Class IV dendritic arborization neurons in Drosophila larvae. Class IV neurons have been shown to sense nociceptive thermal, mechanical and light stimuli, whereas Class I neurons are proprioceptors. We reared larvae on diets with different protein and carbohydrate content throughout larval stages and examined how morphologies of Class I or Class IV neurons were affected. Dendritic arbors of Class IV neurons became more complex when larvae were reared on a low-yeast diet, which contains lower amounts of amino acids and other ingredients, compared to a high-yeast diet. In contrast, such low-yeast-dependent hyperarborization was not seen in Class I neurons. The physiological and metabolic implications of the hyperarborization phenotype are discussed in relation to a recent hypothesis that Class IV neurons sense protein-deficient stress and to our characterization of how the dietary yeast contents impacted larval metabolism. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  13. Single dendrite-targeting interneurons generate branch-specific inhibition.

    Directory of Open Access Journals (Sweden)

    Caleb eStokes

    2014-11-01

    Full Text Available Microcircuits composed of dendrite-targeting inhibitory interneurons and pyramidal cells are fundamental elements of cortical networks, however, the impact of individual interneurons on pyramidal dendrites is unclear. Here, we combine paired recordings and calcium imaging to determine the spatial domain over which single dendrite-targeting interneurons influence pyramidal cells in olfactory cortex. We show that a major action of individual interneurons is to inhibit dendrites in a branch-specific fashion.

  14. Semiautomated analysis of dendrite morphology in cell culture.

    Science.gov (United States)

    Sweet, Eric S; Langhammer, Chris L; Kutzing, Melinda K; Firestein, Bonnie L

    2013-01-01

    Quantifying dendrite morphology is a method for determining the effect of biochemical pathways and extracellular agents on neuronal development and differentiation. Quantification can be performed using Sholl analysis, dendrite counting, and length quantification. These procedures can be performed on dendrite-forming cell lines or primary neurons grown in culture. In this protocol, we describe the use of a set of computer programs to assist in quantifying many aspects of dendrite morphology, including changes in total and localized arbor complexity.

  15. Role of active dendritic conductances in subthreshold input integration

    OpenAIRE

    Rinzel John; Remme Michiel

    2010-01-01

    Dendrites of many types of neurons contain voltage-dependent conductances that are active at subthreshold membrane potentials. To understand the computations neurons perform it is key to understand the role of active dendrites in the subthreshold processing of synaptic inputs. We examine systematically how active dendritic conductances affect the time course of postsynaptic potentials propagating along dendrites, and how they affect the interaction between such signals. Voltage-dependent curr...

  16. Infection of Dendritic Cells by the Maedi-Visna Lentivirus

    OpenAIRE

    Ryan, Susanna; Tiley, Laurence; McConnell, Ian; Blacklaws, Barbara

    2000-01-01

    The early stages of lentivirus infection of dendritic cells have been studied in an in vivo model. Maedi-visna virus (MVV) is a natural pathogen of sheep with a tropism for macrophages, but the infection of dendritic cells has not been proven, largely because of the difficulties of definitively distinguishing the two cell types. Afferent lymphatic dendritic cells from sheep have been phenotypically characterized and separated from macrophages. Dendritic cells purified from experimentally infe...

  17. Actin remodeling and polymerization forces control dendritic spine morphology

    OpenAIRE

    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 (r...

  18. Prevention Effect of Poly-Gamma-Glutamic Acid on Tissue Damage Induced by Gamma Irradiation as a Natural Cross-Linker

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jaehun; Sung, Nakyun; Kim, Jeongsoo; Jo, Euri; Choi, Jongil; Park, Jongheum; Lee, Juwoon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Lee, Kwangwon [Eulji Univ. Hospital, Daejeon (Korea, Republic of); Kwon, Jungkee [Chonbuk National Univ., Jeonju (Korea, Republic of); Kim, Taewoon [Jeonbuk Technopark, Jeonju (Korea, Republic of)

    2012-03-15

    This study was to determine the prevention effect of poly-gamma-glutamic acid (PGA) on tissue damage induced by gamma irradiation for development of xenograft. PGA (MW 2000 kDa) extracted from permeated soy bean (natto) was used in this study as natural compound, and glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were used as a control, chemical based cross-linking agents. GA, EDC and PGA treated porcine tendons were gamma-irradiated at the dose of 30 kGy. Prevention effects against tissue damage were measured as the result of tensile strength, hydroxyproline contents and tissue morphological analysis. Tensile of porcine tendon was remarkably decreased by gamma irradiation, but increased in PGA treated group. Morphological analysis showed that collagen structure was broken by gamma irradiation, but attenuated by PGA treatment. Base on the results, it demonstrated that gamma irradiation can induce severe alteration of porcine tendon, but PGA can effectively improve the tissue damage.

  19. Dendritic Cells Stimulated by Cationic Liposomes.

    Science.gov (United States)

    Vitor, Micaela Tamara; Bergami-Santos, Patrícia Cruz; Cruz, Karen Steponavicius Piedade; Pinho, Mariana Pereira; Barbuto, José Alexandre Marzagão; De La Torre, Lucimara Gaziola

    2016-01-01

    Immunotherapy of cancer aims to harness the immune system to detect and destroy cancer cells. To induce an immune response against cancer, activated dendritic cells (DCs) must present tumor antigens to T lymphocytes of patients. However, cancer patients' DCs are frequently defective, therefore, they are prone to induce rather tolerance than immune responses. In this context, loading tumor antigens into DCs and, at the same time, activating these cells, is a tempting goal within the field. Thus, we investigated the effects of cationic liposomes on the DCs differentiation/maturation, evaluating their surface phenotype and ability to stimulate T lymphocytes proliferation in vitro. The cationic liposomes composed by egg phosphatidylcholine, 1,2-dioleoyl-3-trimethylammonium propane and 1,2-dioleoylphosphatidylethanolamine (50/25/25% molar) were prepared by the thin film method followed by extrusion (65 nm, polydispersity of 0.13) and by the dehydration-rehydration method (95% of the population 107 nm, polydispersity of 0.52). The phenotypic analysis of dendritic cells and the analysis of T lymphocyte proliferation were performed by flow cytometry and showed that both cationic liposomes were incorporated and activated dendritic cells. Extruded liposomes were better incorporated and induced higher CD86 expression for dendritic cells than dehydrated-rehydrated vesicles. Furthermore, dendritic cells which internalized extruded liposomes also provided stronger T lymphocyte stimulation. Thus, cationic liposomes with a smaller size and polydispersity seem to be better incorporated by dendritic cells. Hence, these cationic liposomes could be used as a potential tool in further cancer immunotherapy strategies and contribute to new strategies in immunotherapy.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  2. Sequence learning in differentially activated dendrites

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2003-01-01

    . It is proposed that the neural machinery required in such a learning/retrieval mechanism could involve the NMDA receptor, in conjunction with the ability of dendrites to maintain differentially activated regions. In particular, it is suggested that such a parcellation of the dendrite allows the neuron...... to participate in multiple sequences, which can be learned without suffering from the 'wash-out' of synaptic efficacy associated with superimposition of training patterns. This is a biologically plausible solution to the stability-plasticity dilemma of learning in neural networks....

  3. Seaweed to dendrite transition in directional solidification.

    Science.gov (United States)

    Provatas, Nikolas; Wang, Quanyong; Haataja, Mikko; Grant, Martin

    2003-10-10

    We simulate directional solidification using a phase-field model solved with adaptive mesh refinement. For small surface tension anisotropy directed at 45 degrees relative to the pulling direction we observe a crossover from a seaweed to a dendritic morphology as the thermal gradient is lowered, consistent with recent experimental findings. We show that the morphology of crystal structures can be unambiguously characterized through the local interface velocity distribution. We derive semiempirically an estimate for the crossover from seaweed to dendrite as a function of thermal gradient and pulling speed.

  4. Dendritic Cells Endocytose Bacillus Anthracis Spores: Implications for Anthrax Pathogenesis

    Science.gov (United States)

    2007-11-02

    Dendritic Cells Endocytose Bacillus anthracis Spores: Implications for Anthrax Pathogenesis1 Katherine C. Brittingham,* Gordon Ruthel,* Rekha G...germination and dissemination of spores. Found in high frequency throughout the respiratory track, dendritic cells (DCs) routinely take up foreign...COVERED - 4. TITLE AND SUBTITLE Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax pathogenesis, The Journal of

  5. Fat food for a bad mood. Could we treat and prevent depression in Type 2 diabetes by means of omega-3 polyunsaturated fatty acids?

    DEFF Research Database (Denmark)

    Pouwer, F; Nijpels, G; Beekman, Aartjan T F

    2005-01-01

    complications. CONCLUSIONS: Supplementation with omega-3 PUFA, in particular eicosapentaenoic acid, may be a safe and helpful tool to reduce the incidence of depression and to treat depression in Type 2 diabetes. Further studies are now justified to test these hypotheses in patients with Type 2 diabetes.......AIMS: Evidence strongly suggests that depression is a common complication of Type 2 diabetes mellitus. However, there is considerable room to improve the effectiveness of pharmacological antidepressant agents, as in only 50-60% of the depressed subjects with diabetes does pharmacotherapy lead...... to remission of depression. The aim of the present paper was to review whether polyunsaturated fatty acids (PUFA) of the omega-3 family could be used for the prevention and treatment of depression in Type 2 diabetes. METHODS: MEDLINE database and published reference lists were used to identify studies...

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  8. Dendritic cell maturation and cross-presentation: timing matters!

    Science.gov (United States)

    Alloatti, Andrés; Kotsias, Fiorella; Magalhaes, Joao Gamelas; Amigorena, Sebastian

    2016-07-01

    As a population, dendritic cells (DCs) appear to be the best cross-presenters of internalized antigens on major histocompatibility complex class I molecules in the mouse. To do this, DCs have developed a number of unique and dedicated means to control their endocytic and phagocytic pathways: among them, the capacity to limit acidification of their phagosomes, to prevent proteolytic degradation, to delay fusion of phagosomes to lysosomes, to recruit ER proteins to phagosomes, and to export phagocytosed antigens to the cytosol. The regulation of phagocytic functions, and thereby of antigen processing and presentation by innate signaling, represents a critical level of integration of adaptive and innate immune responses. Understanding how innate signals control antigen cross-presentation is critical to define effective vaccination strategies for CD8(+) T-cell responses.

  9. Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes.

    Directory of Open Access Journals (Sweden)

    Balthasar A Heesters

    2015-12-01

    Full Text Available Despite the success of antiretroviral therapy (ART, it does not cure Human Immunodeficiency Virus (HIV and discontinuation results in viral rebound. Follicular dendritic cells (FDC are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FDC isolated from patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4 T cells in vitro. Importantly, treatment of the HIV+ FDC with a soluble complement receptor 2 purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to achieve cure in HIV-infected humans.

  10. Apoptosis and systemic autoimmunity: the dendritic cell connection

    Directory of Open Access Journals (Sweden)

    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.

  11. [Is folic acid effective for the prevention of cardiovascular events in patients with advanced or terminal chronic kidney disease?].

    Science.gov (United States)

    Peña, José; Claro, Juan Carlos

    2014-05-01

    Patients with chronic kidney disease have an increased cardiovascular risk. Several non-traditional factors have been showed to be associated with this risk, including hyperhomocysteinemia. The effects of reducing homocysteine levels with folic acid supplementation have been studied in a number of randomized trials, with mixed results. In this article we critically appraise two systematic reviews providing disparate conclusions about this question and we summarize their main findings using the GRADE methodology. We conclude that there are methodological differences that may explain the mixed results in both systematic reviews. Folic acid supplementation does not reduce cardiovascular morbidity or mortality in patients with chronic kidney disease at any stage.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Quantitative Determination of Ceramide Molecular Species in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Samar Al Makdessi

    2016-09-01

    Full Text Available Background/Aims: The activation of acid sphingomyelinase by cellular stress or receptors or the de novo synthesis lead to the formation of ceramide (N-acylsphingosine, which in turn modifies the biophysical properties of cellular membrane and greatly amplifies the intensity of the initial signal. Ceramide, which acts by re-organizing a given signalosome rather than being a second messenger, has many functions in infection biology, cancer, cardiovascular syndromes, and immune regulation. Experimental studies on the infection of human cells with different bacterial agents demonstrated the activation of the acid sphingomyelinase/ceramide system. Moreover, the release of ceramide was found to be a requisite for the uptake of the pathogen. Considering the particular importance of the cellular role of ceramide, it was necessary to develop sensitive and accurate methods for its quantification. Methods: Here, we describe a method quantifying ceramide in dendritic cells and defining the different fatty acids (FA bound to sphingosine. The main steps of the method include extraction of total lipids, separation of the ceramide by thin-layer chromatography, derivatization of ceramide-fatty acids (Cer-FA, and quantitation of these acids in their methyl form by gas chromatography on polar capillary columns. The identification of FA was achieved by means of known standards and confirmed by mass spectrometry. Results: FA ranging between C10 and C24 could be detected and quantified. The concentration of the sum of Cer-FA amounted to 14.88 ± 8.98 nmol/106 cells (n=10. Oleic acid, which accounted for approximately half of Cer-FA (7.73 ± 6.52 nmol/106 cells was the predominant fatty acid followed by palmitic acid (3.47 ± 1.54 nmol/106 cells. Conclusion: This highly sensitive method allows the quantification of different molecular species of ceramides.

  14. Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies.

    Science.gov (United States)

    Wilson, R Douglas; Wilson, R Douglas; Audibert, François; Brock, Jo-Ann; Carroll, June; Cartier, Lola; Gagnon, Alain; Johnson, Jo-Ann; Langlois, Sylvie; Murphy-Kaulbeck, Lynn; Okun, Nanette; Pastuck, Melanie; Deb-Rinker, Paromita; Dodds, Linda; Leon, Juan Andres; Lowel, Hélène L; Luo, Wei; MacFarlane, Amanda; McMillan, Rachel; Moore, Aideen; Mundle, William; O'Connor, Deborah; Ray, Joel; Van den Hof, Michiel

    2015-06-01

    Objectif : Offrir des renseignements à jour sur l’utilisation pré et postconceptionnelle d’acide folique par voie orale, avec ou sans supplément de multivitamines / micronutriments, aux fins de la prévention des anomalies du tube neural et d’autres anomalies congénitales. Ces renseignements aideront les médecins, les sages-femmes, les infirmières et les autres professionnels de la santé à contribuer aux efforts de sensibilisation des femmes quant à l’utilisation et aux posologies adéquates de la supplémentation en acide folique / multivitamines, avant et pendant la grossesse. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans PubMed, Medline, CINAHL et la Cochrane Library en janvier 2011 au moyen d’un vocabulaire contrôlé et de mots clés appropriés (p. ex. « folic acid », « prenatal multivitamins », « folate sensitive birth defects », « congenital anomaly risk reduction », « pre-conception counselling »). Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais entre 1985 et juin 2014. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu’en juin 2014. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d’organismes s’intéressant à l’évaluation des technologies dans le domaine de la santé et d’organismes connexes, dans des collections de directives cliniques, dans des registres d’essais cliniques, et auprès de sociétés de spécialité médicale nationales et internationales. Coûts, risques et avantages : Les coûts financiers sont ceux de la supplémentation quotidienne en vitamines et de la consommation d’un régime alimentaire santé enrichi en folate. Les risques sont ceux qui sont li

  15. Interactions with Astroglia Influence the Shape of the Developing Dendritic Arbor and Restrict Dendrite Growth Independent of Promoting Synaptic Contacts

    Science.gov (United States)

    Farley, Jennifer R.; Sterritt, Jeffrey R.; Crane, Andrés B.; Wallace, Christopher S.

    2017-01-01

    Astroglia play key roles in the development of neurons, ranging from regulating neuron survival to promoting synapse formation, yet basic questions remain about whether astrocytes might be involved in forming the dendritic arbor. Here, we used cultured hippocampal neurons as a simple in vitro model that allowed dendritic growth and geometry to be analyzed quantitatively under conditions where the extent of interactions between neurons and astrocytes varied. When astroglia were proximal to neurons, dendrites and dendritic filopodia oriented toward them, but the general presence of astroglia significantly reduced overall dendrite growth. Further, dendritic arbors in partial physical contact with astroglia developed a pronounced pattern of asymmetrical growth, because the dendrites in direct contact were significantly smaller than the portion of the arbor not in contact. Notably, thrombospondin, the astroglial factor shown previously to promote synapse formation, did not inhibit dendritic growth. Thus, while astroglia promoted the formation of presynaptic contacts onto dendrites, dendritic growth was constrained locally within a developing arbor at sites where dendrites contacted astroglia. Taken together, these observations reveal influences on spatial orientation of growth as well as influences on morphogenesis of the dendritic arbor that have not been previously identified. PMID:28081563

  16. NAC1 regulates the recruitment of the proteasome complex into dendritic spines.

    Science.gov (United States)

    Shen, Haowei; Korutla, Laxminarayana; Champtiaux, Nicholas; Toda, Shigenobu; LaLumiere, Ryan; Vallone, Joseph; Klugmann, Matthias; Blendy, Julie A; Mackler, Scott A; Kalivas, Peter W

    2007-08-15

    Coordinated proteolysis of synaptic proteins is required for synaptic plasticity, but a mechanism for recruiting the ubiquitin-proteasome system (UPS) into dendritic spines is not known. NAC1 is a cocaine-regulated transcriptional protein that was found to complex with proteins in the UPS, including cullins and Mov34. NAC1 and the proteasome were cotranslocated from the nucleus into dendritic spines in cortical neurons in response to proteasome inhibition or disinhibiting synaptic activity with bicuculline. Bicuculline also produced a progressive accumulation of the proteasome and NAC1 in the postsynaptic density. Recruitment of the proteasome into dendrites and postsynaptic density by bicuculline was prevented in neurons from mice harboring an NAC1 gene deletion or in neurons transfected with mutated NAC1 lacking the proteasome binding domain. These experiments show that NAC1 modulates the translocation of the UPS from the nucleus into dendritic spines, thereby suggesting a potential missing link in the recruitment of necessary proteolysis machinery for synaptic remodeling.

  17. Pomegranate seed oil, a rich source of punicic acid, prevents diet-induced obesity and insulin resistance in mice.

    NARCIS (Netherlands)

    Vroegrijk, I.O.; Diepen, J.A. van; Berg, S.; Westbroek, I.; Keizer, H.; Gambelli, L.; Hontecillas, R.; Bassaganya-Riera, J.; Zondag, G.C.; Romijn, J.A.; Havekes, L.M.; Voshol, P.J.

    2011-01-01

    BACKGROUND: Pomegranate seed oil has been shown to protect against diet induced obesity and insulin resistance. OBJECTIVE: To characterize the metabolic effects of punicic acid on high fat diet induced obesity and insulin resistance. DESIGN: High-fat diet or high-fat diet with 1% Pomegranate seed oi

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

    Energy Technology Data Exchange (ETDEWEB)

    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 t