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Sample records for profound immunomodulatory properties

  1. Immunomodulatory properties of probiotic bacteria

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen

    2007-01-01

    Certain lactic acid bacteria (LAB) are part of the commensal intestinal flora and considered beneficial for health, as they compete with pathogens for adhesion sites in the intestine and ferment otherwise indigestible compounds. Another important property of these so-called probiotic bacteria...... with bacteria, and the cytokine pattern induced by specific bacteria resembled the pattern induced in MoDC, except for TNF-alpha and IL-6, which were induced in response to different bacteria in blood DC/monocytes and monocyte-derived DC. Autologous NK cells produced IFN-gamma when cultured with blood DC......, monocytes and monocyte-derived DC and IL-12-inducing bacteria, whereas only DC induced IFN-gamma production in allogeneic T cells. In vitro-generated DC is a commonly used model of tissue DC, but they differ in certain aspects from intestinal DC, which are in direct contact with the intestinal microbiota...

  2. IMMUNO-MODULATORY PROPERTIES OF PREBIOTICS EXTRACTED FROM vernonia amygdalina.

    Science.gov (United States)

    Im, Ezeonu; Ae, Asuquo; Bn, Ukwah; Po, Ukoha

    2016-01-01

    Vernonia amygdalina , commonly called bitter-leaf, is widely consumed in many parts of Africa, and Nigeria, in particular. The leaf extract has been reported to have antimicrobial, anti-plasmodial, anti-helminthic, as well as prebiotic properties, but its immuno-modulatory effects have not been well-studied, neither have the prebiotics been identified. This study evaluated the immuno-modulatory properties of the aqueous leaf extract and identified the prebiotic components. The immuno-modulatory potential was evaluated by monitoring the effects of oral administration of the extract on immunological, haematological and lipid profiles of Rattus norvegicus , while the prebiotic components were identified by thin layer chromatography (TLC), following liquid-liquid fractionation of the extract. Consumption of the extract caused significant increases in CD4+-, white blood cell-, total lymphocyte- and high density lipid (HDL) counts; decreases in low density lipid (LDL) and triglycerides and no significant effect on haemoglobin (Hb) and packed cell volume (PCV) in the blood of test animals. The water-soluble fraction of the extract contained most of the phyto-constituents of the extract and Thin Layer Chromatographic analysis of the fraction revealed the presence of fructo-oligosaccharide and galacto-oligosaccharide prebiotics. The results from this study have shown that the aqueous leaf extract of V. amygdalina has positive immune-modulatory and haematologic effects and contains some important prebiotic compounds.

  3. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed.

    Science.gov (United States)

    Salem, Mohamed Labib

    2005-12-01

    A larger number of medicinal plants and their purified constituents have been shown beneficial therapeutic potentials. Seeds of Nigella sativa, a dicotyledon of the Ranunculaceae family, have been employed for thousands of years as a spice and food preservative. The oil and seed constituents, in particular thymoquinine (TQ), have shown potential medicinal properties in traditional medicine. In view of the recent literature, this article lists and discusses different immunomodulatory and immunotherapeutic potentials for the crude oil of N. sativa seeds and its active ingredients. The published findings provide clear evidence that both the oil and its active ingredients, in particular TQ, possess reproducible anti-oxidant effects through enhancing the oxidant scavenger system, which as a consequence lead to antitoxic effects induced by several insults. The oil and TQ have shown also potent anti-inflammatory effects on several inflammation-based models including experimental encephalomyelitis, colitis, peritonitis, oedama, and arthritis through suppression of the inflammatory mediators prostaglandins and leukotriens. The oil and certain active ingredients showed beneficial immunomodulatory properties, augmenting the T cell- and natural killer cell-mediated immune responses. Most importantly, both the oil and its active ingredients expressed anti-microbial and anti-tumor properties toward different microbes and cancers. Coupling these beneficial effects with its use in folk medicine, N. sativa seed is a promising source for active ingredients that would be with potential therapeutic modalities in different clinical settings. The efficacy of the active ingredients, however, should be measured by the nature of the disease. Given their potent immunomodulatory effects, further studies are urgently required to explore bystander effects of TQ on the professional antigen presenting cells, including macrophages and dendritic cells, as well as its modulatory effects upon Th1

  4. [Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

    Science.gov (United States)

    Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

    2015-01-20

    Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  5. Agaricus blazei Murill - immunomodulatory properties and health benefits

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    Biedron R

    2012-11-01

    Full Text Available AbstractThe Agaricus blazei Murill (AbM, also known as Agaricus brasiliensis L. due to its origin in Brazilian rain forest, is an edible mushroom of the Basidiomycetes family, which also comprises medicinal mushrooms such as Hericium erinaceus and Grifola frondosa. AbM has been used in traditional medicine locally and also recently as a health food worldwide. Since it has been found to possess immunomodulatory properties, its biological and health-related effects, as well as its isolated active ingredients e.g. beta-glucans, have been examined by scientists. Otherinvestigations have been performed with mixed mushroom products, such as AndoSanTM, which contains mostly AbM, but also the two other mushrooms above. AbM-related benefits reviewed here include effects against cancer, infections, inflammation, allergy/ asthma and diabetes. Effects of AndoSanTMand other AbM-based extracts have been compared in a bacterial sepsis model.

  6. Immunomodulatory Properties of Streptococcus and Veillonella Isolates from the Human Small Intestine Microbiota

    NARCIS (Netherlands)

    Bogert, van den B.; Meijerink, M.; Zoetendal, E.G.; Wells, J.M.; Kleerebezem, M.

    2014-01-01

    The human small intestine is a key site for interactions between the intestinal microbiota and the mucosal immune system. Here we investigated the immunomodulatory properties of representative species of commonly dominant small-intestinal microbial communities, including six streptococcal strains

  7. Immunomodulatory properties of Alternanthera tenella Colla aqueous extracts in mice

    Directory of Open Access Journals (Sweden)

    R.N.M. Guerra

    2003-09-01

    Full Text Available Plants from the genus Alternanthera are thought to possess antimicrobial and antiviral properties. In Brazilian folk medicine, the aqueous extract of A. tenella Colla is used for its anti-inflammatory activity. The present study investigated the immunomodulatory property of A. tenella extract by evaluating the antibody production in male albino Swiss mice weighing 20-25 g (10 per group. The animals received standard laboratory diet and water ad libitum. The effect of A. tenella extract (5 and 50 mg/kg, ip was evaluated in mice immunized with sheep red blood cells (SRBC 10%, ip as T-dependent antigen, or in mice stimulated with mitogens (10 µg, Escherichia coli lipopolysaccharide, LPS, ip. The same doses (5 and 50 mg/kg, ip of A. tenella extract were also tested for antitumor activity, using the Ehrlich ascites carcinoma as model. The results showed that 50 mg/kg A. tenella extract ip significantly enhanced IgM (64% and IgG2a (50% antibody production in mice treated with LPS mitogen. The same dose had no effect on IgM-specific response, whereas the 5 mg/kg treatment caused a statiscally significant reduction of anti-SRBC IgM-specific antibodies (82%. The aqueous extract of A. tenella (50 mg/kg increased the life span (from 16 ± 1 to 25 ± 1 days and decreased the number of viable tumor cells (59% in mice with Ehrlich ascites carcinoma. The present findings are significant for the development of alternative, inexpensive and perhaps even safer strategies for cancer treatment.

  8. Immuno-modulatory properties of prebiotics extracted from Vernonia ...

    African Journals Online (AJOL)

    Methods: The immuno-modulatory potential was evaluated by monitoring the effects of oral administration of the extract on immunological, haematological and lipid profiles of Rattus norvegicus, while the prebiotic components were identified by thin layer chromatography (TLC), following liquid-liquid fractionation of the ...

  9. Immunomodulatory, antiglycation and anti-ulcerative properties of ...

    African Journals Online (AJOL)

    useful drugs because of their wide functions [15]. Various disease conditions such as infections, organ transplant rejection, cancer, rheumatoid arthritis, and systemic lupus erythematosus are currently treated with immunomodulating agents. [16]. Many plants with immunomodulatory activities have been reported e.g. ...

  10. Amniotic membrane-derived stem cells: immunomodulatory properties and potential clinical application

    Directory of Open Access Journals (Sweden)

    Insausti CL

    2014-03-01

    Full Text Available Carmen L Insausti,1 Miguel Blanquer,1 Ana M García-Hernández,1 Gregorio Castellanos,2 José M Moraleda11Unidad de Trasplante Hematopoyético y Terapia Celular, 2Servicio de Cirugía, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, Campus Mare Nostrum, Universidad de Murcia, El Palmar, Murcia, SpainAbstract: Epithelial and mesenchymal cells isolated from the amniotic membrane (AM possess stem cell characteristics, differentiation potential toward lineages of different germ layers, and immunomodulatory properties. While their expansion and differentiation potential have been well studied and characterized, knowledge about their immunomodulatory properties and the mechanisms involved is still incomplete. These mechanisms have been evaluated on various target cells of the innate and the adaptive system and in animal models of different inflammatory diseases. Some results have evidenced that the immunomodulatory effect of AM-derived cells is dependent on cell-cell contact, but many of them have demonstrated that these properties are mediated through the secretion of suppressive molecules. In this review, we present an update on the described immunomodulatory properties of the derived amniotic cells and some of the proposed involved mechanisms. Furthermore, we describe some assays in animal models of different inflammatory diseases which reveal the potential use of these cells to treat such diseases.Keywords: epithelial cells, mesenchymal cells, cell therapy, immunomodulation

  11. A Leishmania murine model to evaluate the immunomodulatory properties of Pythium insidiosum proteins

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    Tatiana Maria Inêz-Ferreira

    2017-03-01

    Full Text Available Pythium insidiosum immunomodulatory vaccine (PiV has been tested in clinical and experimental pythiosis. Previous data showed that P. insidiosum immunogens have the ability to switch the Th2 immune response, normally in place during pythiosis, to a curative Th1 response. Pythiosis cannot be reproduced in experimental rodents with the exception of rabbits, and thus thorough evaluation of PiV´s immunomodulatory properties has been limited by the lack of a compatible inbred mouse model. In this study, we took advantage of the murine BALB/c Leishmania infection model, where infected mice produce a Th2 response, to evaluate the PiV Th2 to Th1 immunomodulatory potential. Twenty-one days following challenge with L. major, large cutaneous granulomas developed in control mice, consistent with the expected Th2 response. In contrast, Leishmania-induced cutaneous lesions in PiV-immunized mice were minimal or absent. Flow cytometry analysis of spleen cells from mice immunized with PiV and subsequently challenged with L. major displayed more CD4+ and CD8+ cells than the control group. Moreover, spleen cells from mice that were immunized with PiV then challenged with L. major secreted high levels of IFN-γ, with a moderate IL-2, IL-4, and IL-10 mixed cytokine profile upon in vitro re-stimulation with PiV. Anti-P. insidiosum IgG1 in immunized animals was present at low titers suggesting a minor immunological role for this Ig isotype in this model. Our preliminary data showed that BALB/c mice challenged with L. major represent an attractive model in which to study PiV´s immunomodulatory properties.

  12. L-Glutamine in vitro Modulates some Immunomodulatory Properties of Bone Marrow Mesenchymal Stem Cells.

    Science.gov (United States)

    Dos Santos, Guilherme Galvão; Hastreiter, Araceli Aparecida; Sartori, Talita; Borelli, Primavera; Fock, Ricardo Ambrósio

    2017-08-01

    Glutamine (GLUT) is a nonessential amino acid that can become conditionally essential under stress conditions, being able to act in the modulation of the immune responses. Mesenchymal stem cells (MSCs) are known to their capability in the modulation of immune responses through cell-cell contact and by the secretion of soluble factors. Considering that GLUT is an immunonutrient and little is known about the influence of GLUT on the capability of MSCs to modulate immune cells, this work aims to investigate how variations in GLUT concentrations in vitro could affect some immunomodulatory properties of MSCs. In order to evaluate the effects of GLUT on MSCs immunomodulatory properties, cell proliferation rates, the expression of NFκB and STAT-3, and the production of IL-1β, IL-6, IL-10, TGF-β and TNF-α by MSCs were assessed. Based on our findings, GLUT at high doses (10 mM) augmented the proliferation of MSCs and modulated immune responses by decreasing levels of pro-inflammatory cytokines, such as IL-1β and IL-6, and by increasing levels of anti-inflammatory cytokines IL-10 and TGF-β. In addition, MSCs cultured in higher GLUT concentrations (10 mM) expressed lower levels of NF-κB and higher levels of STAT-3. Furthermore, conditioned media from MSCs cultured at higher GLUT concentrations (10 mM) reduced lymphocyte and macrophage proliferation, increased IL-10 production by both cells types, and decreased IFN-γ production by lymphocytes. Overall, this study showed that 10 mM of GLUT is able to modify immunomodulatory properties of MSCs.

  13. Immunomodulatory properties of Concholepas concholepas hemocyanin against francisellosis in a zebrafish model.

    Science.gov (United States)

    Lagos, Leidy; Tandberg, Julia I; Becker, María Inés; Winther-Larsen, Hanne C

    2017-08-01

    The development of vaccines for aquaculture has been an important milestone in providing a continuous and sustainable production. Most of the vaccines currently on the market for aquaculture include oil as adjuvant. Nevertheless, several studies reported an occurrence of side effects after their use in farmed fish. As a result, there is a need for new and improved adjuvants that can stimulate the immune system while causing as few side-effects as possible. Hemocyanins are versatile macromolecules with strong immunogenic and immunomodulatory properties. Due to these characteristics, hemocyanin from Concholepas concholepas (CCH) has been biochemically characterized and evaluated as vaccine adjuvant in mice and humans. Francisellosis is a chronic granulomatous disease, which can result in high mortality depending on the host. The disease is caused by the facultative intracellular Gram-negative bacteria Francisella noatunensis, which remains an unsolved problem for the aquaculture, as no efficient vaccines are available. The aim of the present work was to investigate the immunoregulatory properties of CCH against francisellosis in an experimental zebrafish model. When immunized with CCH, zebrafish were protected from subsequent challenge with a lethal dose of Francisella noatunensis subsp. orientalis. Subsequently the mRNA expression levels of several immune-related genes were studied, including mhcii, il12a, tnfα and ifng1-1. Taken together, the data report the immunoregulatory properties of CCH and its potential use as a vaccine adjuvant for aquaculture. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Curcumin-albumin conjugates as an effective anti-cancer agent with immunomodulatory properties.

    Science.gov (United States)

    Aravind, S R; Krishnan, Lissy K

    2016-05-01

    Curcumin (diferuloylmethane) is an active ingredient in turmeric (Curcuma longa) with anti-inflammatory, antioxidant, chemopreventive, chemosensitization, and radiosensitization properties. Conjugation of curcumin (Curc) to albumin (Alb) has been found to increase the aqueous solubility of the drug. The current study aimed to prove the safe use of the Curc-Alb conjugate in animals and to demonstrate that it retains drug action both in vitro and in vivo. Dalton's lymphoma ascites (DLA) cell viability was inhibited by the Curc-Alb conjugate in a dose dependent manner in vitro, as evidenced by the MTT assay. Administration of up to 11.4 mg of conjugated curcumin per kg body weight to healthy animals was non-toxic both in terms of lethality and weight loss. Histological analysis of vital organs (kidney, liver and spleen) also did not show toxic effects. Favorable immuno-modulatory activity was observed after continuous administration of sub-acute doses of the conjugate which caused increase in total leukocyte count, platelet count, and viable cell count in bone marrow, and enhanced proliferation of lymphocyte in vitro upon culture. In vivo studies in the DLA tumor model in mice demonstrated that conjugated drug induces tumor reduction and prevention. Significant tumor reduction was observed when the Curc-Alb conjugate was administered intraperitoneally in DLA-induced mice after 1 day (prevention therapy) and 7 days (reduction therapy) of tumor induction. There was significant reduction in both tumor volume and tumor cell numbers in the treated animals as well as a marked increase in their mean survival time and percent increase in life span. The effect was greater when the conjugate was administered soon after inducing the tumor as compared to when treatment was started after allowing tumor to grow for 7 days. Thus, the results of the present study suggest that curcumin albumin conjugate has immunomodulatory and tumor growth inhibition properties. The study postulates

  15. Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

    International Nuclear Information System (INIS)

    Rödel, Franz; Frey, Benjamin; Manda, Katrin; Hildebrandt, Guido; Hehlgans, Stephanie; Keilholz, Ludwig; Seegenschmiedt, M. Heinrich; Gaipl, Udo S.; Rödel, Claus

    2012-01-01

    Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

  16. Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Rödel, Franz [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany); Frey, Benjamin [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen (Germany); Manda, Katrin; Hildebrandt, Guido [Department of Radiotherapy and Radiation Oncology, University of Rostock, Rostock (Germany); Hehlgans, Stephanie [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany); Keilholz, Ludwig [Department of Radiotherapy, Clinical Center Bayreuth, Bayreuth (Germany); Seegenschmiedt, M. Heinrich [Strahlenzentrum Hamburg Medizinisches Versorgungszentrum, Hamburg (Germany); Gaipl, Udo S. [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen (Germany); Rödel, Claus, E-mail: franz.roedel@kgu.de [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany)

    2012-09-25

    Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

  17. Structural analyses and immunomodulatory properties of fructo-oligosaccharides from onion (Allium cepa).

    Science.gov (United States)

    Kumar, V Prasanna; Prashanth, K V Harish; Venkatesh, Y P

    2015-03-06

    Onion (Allium cepa) is an immune-boosting food rich in fructans. The major aim of this study is to characterize and investigate the immunomodulatory properties of onion fructo-oligosaccharides (FOS). FOS was isolated from onion bulbs by hot 80% ethanol extraction (yield: ∼4.5 g/100 g fw) followed by gel permeation chromatography. NMR of onion FOS revealed unusual β-D-Glc terminal residue at the non-reducing end. TLC and ESI-MS analyses showed that onion FOS ranged from trisaccharides to hexasaccharides. Onion FOS (50 μg/mL) significantly increased (∼3-fold) the proliferation of mouse splenocytes/thymocytes vs. control. Further, onion FOS enhanced (∼2.5-fold) the production of nitric oxide by peritoneal exudates cells (PECs) from Wistar rats; intracellular free radicals production and phagocytic activity of isolated murine PECs were also augmented. Our structural and in vitro results indicate that onion FOS comprising of tri- to hexasaccharide units belongs to inulin-type fructans, and possess immunostimulatory activities towards murine lymphocytes and macrophages. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Microgramma vacciniifolia (Polypodiaceae) fronds contain a multifunctional lectin with immunomodulatory properties on human cells.

    Science.gov (United States)

    de Siqueira Patriota, Leydianne Leite; Procópio, Thamara Figueiredo; de Santana Brito, Jéssica; Sebag, Virginie; de Oliveira, Ana Patrícia Silva; de Araújo Soares, Ana Karine; Moreira, Leyllane Rafael; de Albuquerque Lima, Thâmarah; Soares, Tatiana; da Silva, Túlio Diego; Paiva, Patrícia Maria Guedes; de Lorena, Virgínia Maria Barros; de Melo, Cristiane Moutinho Lagos; de Albuquerque, Lidiane Pereira; Napoleão, Thiago Henrique

    2017-10-01

    In this study, we report the purification and characterization of a multifunctional lectin (MvFL) from Microgramma vacciniifolia fronds as well as its immunomodulatory properties on human peripheral blood mononuclear cells (PBMCs). MvFL (pI 4.51; 54kDa) is a glycoprotein able to inhibit trypsin activity and that has sequence similarities (32% coverage) with a plant RNA-binding protein. Hemagglutinating activity of MvFL was not altered by heating at 100°C for 30min, but was reduced in alkaline pH (8.0 and 9.0). Fluorimetric analyses showed that this lectin did not undergo marked conformational changes when heated. However, the MvFL conformation changed depending on the pH. MvFL at 6.25-25μg/mL was not cytotoxic to lymphocytes present among PBMCs. The PBMCs incubated for 24h with the lectin (12.5μg/mL) showed increased TNF-α, IFN-γ, IL-6, IL-10, and nitric oxide production. MvFL also stimulated T lymphocytes from PBMCs to differentiate into CD8 + cells. The activation (indicated by CD28 expression) of these cells was also stimulated. In conclusion, MvFL is a heat-stable and multifunctional protein, with both lectin and trypsin inhibitor activities, and capable of inducing predominantly a Th1 response in human PBMCs as well as activation and differentiation of T lymphocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Effects of hypoxia on the immunomodulatory properties of adipose tissue-derived mesenchymal stem cells

    NARCIS (Netherlands)

    M. Roemeling-Van Rhijn (Marieke); F.K.F. Mensah (Fane ); S.S. Korevaar (Sander); M.J.C. Leijs (Maarten J.C.); G.J.V.M. van Osch (Gerjo); J.N.M. IJzermans (Jan); M.G.H. Betjes (Michiel); C.C. Baan (Carla); W. Weimar (Willem); M.J. Hoogduijn (Martin)

    2013-01-01

    textabstractAdipose tissue-derived mesenchymal stem cells (ASC) are of great interest as a cellular therapeutic agent for regenerative and immunomodulatory purposes. The function of ASC adapts to environmental conditions, such as oxygen tension. Oxygen levels within tissues are typically much lower

  20. Dextran: Influence of Molecular Weight in Antioxidant Properties and Immunomodulatory Potential.

    Science.gov (United States)

    Soeiro, Vinicius C; Melo, Karoline R T; Alves, Monique G C F; Medeiros, Mayara J C; Grilo, Maria L P M; Almeida-Lima, Jailma; Pontes, Daniel L; Costa, Leandro S; Rocha, Hugo A O

    2016-08-19

    Dextrans (α-d-glucans) extracted from Leuconostoc mesenteroides, with molecular weights (MW) of 10 (D10), 40 (D40) and 147 (D147) kDa, were evaluated as antioxidant, anticoagulant and immunomodulatory drugs for the first time. None presented anticoagulant activity. As for the antioxidant and immunomodulatory tests, a specific test showed an increase in the dextran activity that was proportional to the increase in molecular weight. In a different assay, however, activity decreased or showed no correlation to the MW. As an example, the reducing power assay showed that D147 was twice as potent as other dextrans. On the other hand, all three samples showed similar activity (50%) when it came to scavenging the OH radical, whereas only the D10 sample showed sharp activity (50%) when it came to scavenging the superoxide ion. D40 was the single dextran that presented with immunomodulatory features since it stimulated the proliferation (~50%) of murine macrophages (RAW 264.7) and decreased the release of nitric oxide (~40%) by the cells, both in the absence and presence of lipopolysaccharides (LPS). In addition, D40 showed a greater scavenging activity (50%) for the hydrogen peroxide, which caused it to also be the more potent dextran when it came to inhibiting lipid peroxidation (70%). These points toward dextrans with a 40 kDa weight as being ideal for antioxidant and immunomodulatory use. However, future studies with the D40 and other similarly 40 kDa dextrans are underway to confirm this hypothesis.

  1. The immunomodulatory effect of plant lectins: a review with emphasis on ArtinM properties.

    Science.gov (United States)

    Souza, Maria A; Carvalho, Fernanda C; Ruas, Luciana P; Ricci-Azevedo, Rafael; Roque-Barreira, Maria Cristina

    2013-10-01

    Advances in the glycobiology and immunology fields have provided many insights into the role of carbohydrate-protein interactions in the immune system. We aim to present a comprehensive review of the effects that some plant lectins exert as immunomodulatory agents, showing that they are able to positively modify the immune response to certain pathological conditions, such as cancer and infections. The present review comprises four main themes: (1) an overview of plant lectins that exert immunomodulatory effects and the mechanisms accounting for these activities; (2) general characteristics of the immunomodulatory lectin ArtinM from the seeds of Artocarpus heterophyllus; (3) activation of innate immunity cells by ArtinM and consequent induction of Th1 immunity; (4) resistance conferred by ArtinM administration in infections with intracellular pathogens, such as Leishmania (Leishmania) major, Leishmania (Leishmania) amazonensis, and Paracoccidioides brasiliensis. We believe that this review will be a valuable resource for more studies in this relatively neglected area of research, which has the potential to reveal carbohydrate targets for novel prophylactic and therapeutic strategies.

  2. Comparison of the Immunomodulatory Properties of Root and Leaves of Arctium Lappa (Burdock in Vitro

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    Hasan Namdar Ahmadabad

    2017-10-01

    Full Text Available Background: The roots and leaves of Arctium lappa (burdock have been used for different therapeutic purposes, especially for diseases linked to chronic inflammation. Objectives: The present study was designed to evaluate and compare the immunomodulatory activities of root extract of burdock and leaves extract of burdock in vitro. Methods: In this experimental study, PHA- or LPS-stimulated splenocytes were treated with different concentrations of root or leaves extract of burdock and proliferation of splenocytes measured by MTT assay. The levels of IFN-γ and IL4 in the supernatants of PHA-stimulated splenocytes determined using ELISA. We also studied the effects of root and leaves extract of burdock on Nitric Oxide production by LPS-stimulated macrophages using the Griess reagent. The data were analyzed by one-way ANOVA followed by Tukey’s post-test using GraphPad Prism software, version 5.0. Results: Our findings showed that both root and leaves extract of burdock have suppressive effects on LPS-stimulated splenocytes proliferation, IL-4 secretion from PHA-stimulated splenocytes, and NO production from LPS-stimulated macrophage and stimulatory effects on PHA-stimulated splenocytes proliferation, and IFN-γ secretion from PHA-stimulated splenocytes. Although both root and leaves extract of burdock had similar immunomodulatory effects in vitro, stronger immunomodulatory effects seen in root extract of burdock. Conclusions: According to our results, we suggest that root of burdock is better option than leaves of burdock in modulation immune responses and inflammations.

  3. Immunomodulatory Properties of Carvone Inhalation and Its Effects on Contextual Fear Memory in Mice

    Science.gov (United States)

    Lasarte-Cia, Aritz; Lozano, Teresa; Pérez-González, Marta; Gorraiz, Marta; Iribarren, Kristina; Hervás-Stubbs, Sandra; Sarobe, Pablo; Rabal, Obdulia; Cuadrado-Tejedor, Mar; García-Osta, Ana; Casares, Noelia; Lasarte, Juan José

    2018-01-01

    A complex network of interactions exists between the immune, the olfactory, and the central nervous system (CNS). Inhalation of different fragrances can affect immunological reactions in response to an antigen but also may have effects on the CNS and cognitive activity. We performed an exploratory study of the immunomodulatory ability of a series of compounds representing each of the 10 odor categories or clusters described previously. We evaluated the impact of each particular odor on the immune response after immunization with the model antigen ovalbumin in combination with the TLR3 agonist poly I:C. We found that some odors behave as immunostimulatory agents, whereas others might be considered as potential immunosuppressant odors. Interestingly, the immunomodulatory capacity was, in some cases, strain-specific. In particular, one of the fragrances, carvone, was found to be immunostimulatory in BALB/c mice and immunosuppressive in C57BL/6J mice, facilitating or impairing viral clearance, respectively, in a model of a viral infection with a recombinant adenovirus. Importantly, inhalation of the odor improved the memory capacity in BALB/c mice in a fear-conditioning test, while it impaired this same capacity in C57BL/6J mice. The improvement in memory capacity in BALB/c was associated with higher CD3+ T cell infiltration into the hippocampus and increased local expression of mRNA coding for IL-1β, TNF-α, and IL-6 cytokines. In contrast, the memory impairment in C57BL/6 was associated with a reduction in CD3 numbers and an increase in IFN-γ. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals. These results highlight the potential of studying odors as therapeutic agents for CNS-related diseases. PMID:29422905

  4. Isolation and immunomodulatory properties of a flavonoid, casticin from Vitex agnus-castus.

    Science.gov (United States)

    Mesaik, M Ahmed; Murad, Shahnaz; Khan, Khalid Mohammed; Tareen, Rasool Bakhsh; Ahmed, Aqeel; Choudhary, Muhammad Iqbal

    2009-11-01

    Casticin (1), a flavonoid isolated from the aerial parts of Vitex agnus-castus, was found to be a potent immunomodulatory and cytotoxic compound. The activity was tested in vitro for chemiluminescence, chemotaxis, T-cell proliferation and cytotoxicity. Casticin (1) exhibited a significant inhibitory effect on monocyte oxidative burst in a dose dependent manner. It was found to have a significant suppressive effect on the chemotaxic action at higher concentrations on fMLP (10(-8) m) stimulated neutrophils. It also showed a potent suppressive effect on PHA stimulated T-cell (PMBC).

  5. Assessment of Physicochemical Properties of Rituximab Related to Its Immunomodulatory Activity

    Directory of Open Access Journals (Sweden)

    Mariana P. Miranda-Hernández

    2015-01-01

    Full Text Available Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

  6. Immunomodulatory properties of fermented soy and dairy milks prepared with lactic acid bacteria.

    Science.gov (United States)

    Wagar, L E; Champagne, C P; Buckley, N D; Raymond, Y; Green-Johnson, J M

    2009-10-01

    Fermented soy and dairy milk preparations provide a means for delivering lactic acid bacteria and their fermentation products into the diet. Our aims were to test immunomodulatory bioactivity of fermented soy beverage (SB) and dairy milk blend (MB) preparations on human intestinal epithelial cells (IEC) and to determine the impact of freezing medium on culture survival prior to bioactivity analyses. Fermented SB and MB were prepared using pure or mixed cultures of Streptococcus thermophilus ST5, Bifidobacterium longum R0175, and Lactobacillus helveticus R0052. Immunomodulatory bioactivity was assessed by testing selected SB and MB ferments on tumor necrosis factor alpha (TNFalpha)-treated IEC and measuring effects on Interleukin-8 (IL-8) production. Impact of timing of ferment administration relative to this pro-inflammatory challenge was investigated. The most pronounced reductions in IEC IL-8 production were observed when IEC were treated with either SB or MB ferment preparations prior to TNFalpha challenge. These results indicate that freezing-stable MB and SB ferments prepared with selected strains can modulate IEC IL-8 production in vitro, and suggest that yogurt-like fermented soy formulations could provide a functional food alternative to milk-based fermented products.

  7. Immunomodulatory activities and antioxidant properties of polysaccharides from Monascus-fermented products in vitro.

    Science.gov (United States)

    Tseng, Kuo-Chuan; Fang, Tony J; Chiang, Shen-Shih; Liu, Chin-Feng; Wu, Cheng-Lun; Pan, Tzu-Ming

    2012-05-01

    Monascus-fermented products have featured in Chinese cuisine for thousands of years and are widely used as food colourants and dietary materials in many Asian countries. Rice and dioscorea fermented with Monascus purpureus NTU 568 have health-promoting attributes in vitro and in vivo. The aim of this study was to investigate the immunomodulatory and antioxidant effects of polysaccharides from red mould rice (RMRP) and red mould dioscorea (RMDP) in Raw 264.7 cells. The results showed the antioxidant capabilities (including scavenging, chelating, inhibition of lipid peroxidation, and reducing power) of RMRP and RMDP at a concentration of 10 mg mL(-1). RMRP and RMDP also stimulated cell proliferation, nitric oxide production, phagocytosis and cytokine production (including IL1-β, IL-6 and TNF-α) in Raw 264.7 cells. These findings demonstrate that RMRP and RMDP have antioxidant and immunomodulation potential to be developed as novel dietary supplements. Copyright © 2011 Society of Chemical Industry.

  8. Environmentally profound

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Rushu [China Yangzte Three Gorges Project Development Corp., Yichang Hubei (China)

    1999-09-01

    The Three Gorges dam project on the Yangtze river will have a profound effect on the people, the environment and cultural heritage sites. The dam will be the world's biggest and will provide almost 85 BkWh of hydro power per annum. A noticeable benefit will be a greatly reduced incidence of flooding in the Jingjiang reaches of the river. Additional benefits will be improved local navigation, climate and enhanced water quality. The main unwelcome impacts were loss of farmland and resettlement of people but here the government have been particularly careful to provide the relocated people with a reasonable standard of new accommodation and farmland. The loss of natural vegetation will be small but there are endangered species of birds and animals living in the region. A number of negative environmental affects (dust noise, incidence of certain diseases) and how they are to be mitigated are mentioned. (UK)

  9. The effects of hyperthermia on the immunomodulatory properties of human umbilical cord vein mesenchymal stem cells (MSCs).

    Science.gov (United States)

    Hesami, Shilan; Mohammadi, Mehdi; Rezaee, Mohamad Ali; Jalili, Ali; Rahmani, Mohammad Reza

    2017-11-01

    Hyperthermia can modulate inflammation and the immune response. Based on the recruitment of mesenchymal stem cells (MSCs) to inflamed tissues and the immunomodulatory properties of these cells, the aim of this study was to examine the effects of hyperthermia on the immunomodulatory properties of MSCs in a mixed lymphocyte reaction (MLR). Passages 4-6 of human umbilical cord vein mesenchymal stem cells were co-cultured in a two-way MLR. Cells in the hyperthermia groups were incubated at 41 °C for 45 min. A colorimetric assay was employed to examine the effects of MSCs on cell proliferation. The levels of IL-4 and TNF-α proteins in the cell culture supernatant were measured, and non-adherent cells were used for RNA extraction, which was then used for cDNA synthesis. RT-PCR was utilised to assess levels of IL-10, IL-17A, IL-4, TNF-α, TGF-β1, FOX P 3 , IFN-γ, CXCL12 and β-actin mRNA expression. UCV-MSCs co-cultured in an MLR reduced lymphocyte proliferation at 37 °C, whereas hyperthermia attenuated this effect. Hyperthermia increased expression of IL-10, TGF-β1 and FOXP3 mRNAs in co-culture; however, no effects on IL-17A and IFN-γ were observed, and it reduced CXCL12 expression. In co-culture, IL-4 mRNA and protein increased at 37 °C, an effect that was reduced by hyperthermia. No considerable change in TNF-α mRNA expression was found in hyperthermia-treated cells. Hyperthermia increases cell proliferation of the peripheral blood mononuclear cells and modifies the cytokine profile in the presence of UCV-MSCs.

  10. Surface modifications of silica nanoparticles are crucial for their inert versus proinflammatory and immunomodulatory properties

    Directory of Open Access Journals (Sweden)

    Marzaioli V

    2014-06-01

    Full Text Available Viviana Marzaioli,1 Juan Antonio Aguilar-Pimente,1,2 Ingrid Weichenmeier,1 Georg Luxenhofer,3 Martin Wiemann,4 Robert Landsiedel,5 Wendel Wohlleben,5 Stefanie Eiden,6 Martin Mempel,7 Heidrun Behrendt,1 Carsten Schmidt-Weber,1 Jan Gutermuth,1,8 Francesca Alessandrini1 1Center of Allergy and Environment (ZAUM, Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL, Munich, Germany; 2Department of Dermatology and Allergy Biederstein, Technische Universität München (TUM and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany, 3Institute of Developmental Genetics, Helmholtz Zentrum München, Neuherberg, Germany; 4IBE R&D gGmbH, Münster, Germany; 5BASF, Ludwigshafen, Germany; 6Bayer Technology Services, Leverkusen, Germany; 7Department of Dermatology, Venereology and Allergology, Universitätsmedizin Göttingen (UMG, Göttingen, Germany; 8Department of Dermatology, Vrije Universiteit Brussel, Brussels, Belgium Background: Silica (SiO2 nanoparticles (NPs are widely used in diverse industrial and biomedical applications. Their applicability depends on surface modifications, which can limit potential health problems. Objective: To assess the potential impact of SiO2 NP exposure and NPs chemical modifications in allergic airway inflammation. Methods: Mice were sensitized by five repetitive intraperitoneal injections of ovalbumin/aluminum hydroxide (1 µg over 42 days, then intratracheally instilled with plain or modified SiO2 NPs (50 µg/mouse, and subsequently aerosol challenged for 20 minutes with ovalbumin. One or 5 days later, allergic inflammation was evaluated by cell differentiation of bronchoalveolar lavage fluid, lung function and gene expression and histopathology, as well as electron and confocal microscopy of pulmonary tissue. Results: Plain SiO2 NPs induced proinflammatory and immunomodulatory effects in vivo

  11. Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner.

    Science.gov (United States)

    Munir, Hafsa; Ward, Lewis S C; Sheriff, Lozan; Kemble, Samuel; Nayar, Saba; Barone, Francesca; Nash, Gerard B; McGettrick, Helen M

    2017-06-01

    Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage-induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC isolated from bone marrow or adipose tissue on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue. Bone marrow derived MSC were immunosuppressive, inhibiting neutrophil recruitment to TNFα-treated endothelial cells (EC), but MSC-derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL-6 and TGFβ1 signalling appeared critical for the loss of the immunosuppressive phenotype. In contrast, native stromal cells, adipocytes derived from them, and mature adipocytes from adipose tissue were all immunoprotective. Thus disruption of normal tissue stroma homeostasis, as occurs in chronic inflammatory diseases, might drive "abnormal" adipogenesis which adversely influences the behavior of MSC and contributes to pathogenic recruitment of leukocytes. Interestingly, stromal cells programmed in native fat tissue retain an immunoprotective phenotype. Stem Cells 2017;35:1636-1646. © 2017 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  12. Isolation of Phytochemicals from Cordia rothii (Boraginaceae and Evaluation of their Immunomodulatory Properties

    Directory of Open Access Journals (Sweden)

    Sadiqa Firdous

    2014-01-01

    Full Text Available n -Hexane, EtOAc, and BuOH fractions obtained from methanol extract of leaves of Cordia rothii Roem and Schult, yielded 1-octacosanol (1, β-sitosterol (2, stigmast-5-en-3-O-β- D -glucoside (3, (2S,1′S,2′S,3′R,7′Z-N-1′-(O-β- D -glucopyranosylmethyl-2′,3′-dihydroxy-heptadec-7′-enyl-2-hydroxytetracosane-amide (4, methyl 2-hydroxy-3-(4′-hydroxy-phenyl propionate (5, (2R-(4-hydroxyphenyllactic acid (6, syringaresinol mono-β- D -glucoside (7, 6-hydroxy-3-oxo-α-ionol 9-O-β- D -glucopyranoside (8, staphylionoside D (9, and 3-(3′,5′-dimethoxy-4′-O-β- D -glucopyranosyl-phenyl-prop-2E-en-1-ol (10. To the best of our knowledge, all compounds except 2 are reported for the first time from this source. Norterpenoid, lignan, cerebroside, and megastigmane are also reported for the first time. Immunomodulatory activity was evaluated using oxidative burst; phytohaemagglutinin (PHA stimulated T-cell proliferation and nitric oxide (NO assays. EtOAc fraction exhibited significant inhibitory activity against ROS with IC 50 value of 29.4 ± 2.8 µg/mL. n-Hexane fraction exhibited very strong suppressive effect on PHA stimulated T-cell proliferation with IC 50 value of 85% inhibition. Compound 7 exhibited significant inhibitory activity (IC 50 = 11.3 and 18.0 on PMN and whole blood respectively on zymosan activated ROS generation. Eight sub-fractions showed potent inhibitory activity on the NO with >60% inhibition. These results suggest that compounds from C. rothii could be potential inhibitor for the mediators involved in innate and adaptive immune responses, and potential anti-inflammatory agents.

  13. The immunomodulatory properties of viable Lactobacillus salivarius ssp. salivarius CECT5713 are not restricted to the large intestine.

    Science.gov (United States)

    Arribas, Belén; Garrido-Mesa, Natividad; Perán, Laura; Camuesco, Desirée; Comalada, Mònica; Bailón, Elvira; Olivares, Mónica; Xaus, Jordi; Kruidenier, Laurens; Sanderson, Ian R; Zarzuelo, Antonio; Rodríguez-Cabezas, Maria Elena; Gálvez, Julio

    2012-04-01

    The aim of this study was to better characterise the biological effects of Lactobacillus salivarius ssp. salivarius CECT5713, a probiotic with immunomodulatory properties. Live or dead probiotic was assayed in the TNBS model of rat colitis to determine whether viability was a requisite to exert the beneficial effects. In vitro studies were also performed in Caco-2 cells to evaluate its effects on epithelial cell recovery and IL-8 production. Finally, the probiotic was assayed in the LPS model of septic shock in mice to establish its effects when there is an altered systemic immune response. The viability of the probiotic was required for its anti-inflammatory activity. The probiotic inhibited IL-8 production in stimulated Caco-2 cells and facilitated the recovery of damaged intestinal epithelium. In LPS-treated mice, the probiotic inhibited the production of TNFα in plasma and lungs and increased the hepatic glutathione content. These effects were associated with an improvement in the altered production of the T-cell cytokines in splenocytes, by reducing IL-2 and IL-5 and by increasing IL-10. Finally, it reduced the increased plasma IgG production in LPS-treated mice. The anti-inflammatory effects of viable L. salivarius ssp. salivarius CECT5713 are not restricted to the gastrointestinal tract.

  14. The Immunomodulatory Properties of Amniotic Cells: The Two Sides of the Coin.

    Science.gov (United States)

    Magatti, Marta; Vertua, Elsa; Cargnoni, Anna; Silini, Antonietta; Parolini, Ornella

    2018-01-01

    Among the many cell types useful in developing therapeutic treatments, human amniotic cells from placenta have been proposed as valid candidates. Both human amniotic epithelial and mesenchymal stromal cells, and the conditioned medium generated from their culture, exert multiple immunosuppressive activities. Indeed, they inhibit T and B cell proliferation, suppress inflammatory properties of monocytes, macrophages, dendritic cells, neutrophils, and natural killer cells, while promoting induction of cells with regulatory functions such as regulatory T cells and anti-inflammatory M2 macrophages. These properties have laid the foundation for their use for the treatment of inflammatory-based diseases, and encouraging results have been obtained in different preclinical disease models where exacerbated inflammation is present. Moreover, an immune-privileged status of amniotic cells has been often highlighted. However, even if long-term engraftment of amniotic cells has been reported into immunocompetent animals, only few cells survive after infusion. Furthermore, amniotic cells have been shown to be able to induce immune responses in vivo and, under specific culture conditions, they can stimulate T cell proliferation in vitro. Although immunosuppressive properties are a widely recognized characteristic of amniotic cells, immunogenic and stimulatory activities appear to be less reported, sporadic events. In order to improve therapeutic outcome, the mechanisms responsible for the suppressive versus stimulatory activity need to be carefully addressed. In this review, both the immunosuppressive and immunostimulatory activity of amniotic cells will be discussed.

  15. Immunomodulatory properties of 1,2-dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15.

    Science.gov (United States)

    Malfitano, Anna Maria; Laezza, Chiara; Bertini, Simone; Marasco, Daniela; Tuccinardi, Tiziano; Bifulco, Maurizio; Manera, Clementina

    2017-04-01

    1,2-Dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15 has been recently developed as a selective cannabinoid CB2 receptor compound. Given the high selectivity of this compound at the cannabinoid CB2 receptor and the well-known protective function of this receptor in neurological disorders with autoimmune component like multiple sclerosis, we assessed the immunomodulatory properties of VL15. We assessed on activated peripheral blood mononuclear cells), proliferation and viability, cell cycle progression and measured activation markers and the expression of phosphorylated proteins. We found that VL15 reduces PBMC proliferation slightly affecting cell vitality, blocks the cell cycle progression and down-regulates the levels of T cell activation markers as well as the expression of phosphorylated proteins, NF-kB, IKKαβ, IKBα, ERK and Akt. VL15 was also used in drug-permeability assays on Caco-2 cell line to evaluate its oral bioavailability and on MDCKII-hMDR1 cell lines to estimate its propensity to cross the blood-brain barrier by passive diffusion, in order to potentially maintain its efficiency on the infiltrating auto-reactive lymphocytes in the central nervous system. In these models, VL15 showed high intestinal absorption and good blood-brain barrier penetration. Our findings suggest that VL15, by controlling the immune response, might find potential application as orally administered drug in pathologies like multiple sclerosis. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  16. Activation of spleen cells by ArtinM may account for its immunomodulatory properties.

    Science.gov (United States)

    Silva, Thiago Aparecido da; Souza, Maria Aparecida de; Cecílio, Nerry Tatiana; Roque-Barreira, Maria Cristina

    2014-09-01

    ArtinM is a D-mannose-binding lectin extracted from Artocarpus heterophyllus that promotes interleukin-12 production by macrophages and dendritic cells. This property is considered responsible for T helper 1 immunity induced in vivo after ArtinM administration. In this study, we investigated the effect of native (jArtinM) and recombinant (rArtinM) forms of lectin on murine spleen cells and isolated T lymphocytes. We found that ArtinM binds to the surface of spleen cells. This interaction, which was blocked by D-mannose, induced cell activation, as manifested by increased mitochondrial activity, interleukin-2 production, and cell proliferation. We verified that a 30-times higher concentration of rArtinM was required to trigger optimal activation of spleen cells compared with that needed with jArtinM, although these proteins have identical sugar recognition properties and use the same signaling molecules to trigger cell activation. Because the distinction between native and recombinant is restricted to their tertiary structure (tetrameric and monomeric, respectively), we postulated that the multi-valence of jArtinM accounts for its superiority in promoting clustering of cell surface glycoreceptors and activation. The jArtinM and rArtinM activation effect exerted on spleen cells was reproduced on purified CD4(+) T cells. Our results suggest that ArtinM interaction with T cells leads to responses that may act in concert with the interleukin-12 produced by antigen-presenting cells to modulate immunity toward the T helper 1 axis. Further studies are necessary to dissect ArtinM/T-cell interactions to more fully understand the immunomodulation induced by carbohydrate recognition.

  17. Immunomodulatory properties of cacao extracts – potential consequences for medical applications

    Science.gov (United States)

    Becker, Kathrin; Geisler, Simon; Ueberall, Florian; Fuchs, Dietmar; Gostner, Johanna M.

    2013-01-01

    Anti-inflammatory properties of cacao, fruits of Theobroma cacao L. (Sterculiaceae), are well documented, and therapeutic applications are described for gastrointestinal, nervous, and cardiovascular abnormalities. Most, if not all of these disease conditions involve inflammation or immune activation processes. The pro-inflammatory cytokine interferon-γ (IFN-γ) and related biochemical pathways like tryptophan breakdown by indoleamine 2,3-dioxygenase (IDO) and neopterin formation are deeply involved in their pathogenesis. Neopterin concentrations and the kynurenine to tryptophan ratio (Kyn/Trp, an estimate of IDO activity) are elevated in a significant proportion of patients with virus infections, cancer, autoimmune syndrome, neurodegeneration, and coronary artery disease. Moreover, higher neopterin and Kyn/Trp concentrations are indicative for poor prognosis. When investigating the effect of aqueous or ethanolic extracts of cacao on IFN-γ, neopterin and Kyn/Trp concentrations in mitogen-stimulated human peripheral blood mononuclear cells, breakdown of tryptophan by IDO, and formation of neopterin and IFN-γ were dose-dependently suppressed. The effects observed in the cell-based assays are associated with the antioxidant activity of the cacao extracts as determined by the cell-free oxygen radical absorption capacity assay. The influence of cacao extracts on IDO activity could be of particular relevance for some of the beneficial health effects ascribed to cacao: tryptophan breakdown by IDO is strongly involved in immunoregulation, and the diminished availability of tryptophan limits the biosynthesis of neurotransmitter serotonin. The inhibition of tryptophan breakdown by cacao constituents could thus be relevant not only for immune system restoration in patients, but also contribute to mood elevation and thereby improve quality of life. However, the available data thus far are merely in vitro only and future studies need to investigate the influence of cacao on

  18. Activation of human mast cells by retrocyclin and protegrin highlight their immunomodulatory and antimicrobial properties.

    Science.gov (United States)

    Gupta, Kshitij; Kotian, Akhil; Subramanian, Hariharan; Daniell, Henry; Ali, Hydar

    2015-10-06

    Preclinical evaluation of Retrocyclins (RC-100, RC-101) and Protegrin-1 (PG-1) antimicrobial peptides (AMPs) is important because of their therapeutic potential against bacterial, fungal and viral infections. Human mast cells (HMCs) play important roles in host defense and wound healing but the abilities of retrocyclins and protegrin-1 to harness these functions have not been investigated. Here, we report that chemically synthesized RC-100 and PG-1 caused calcium mobilization and degranulation in HMCs but these responses were not blocked by an inhibitor of formyl peptide receptor-like 1 (FPRL1), a known receptor for AMPs. However, RC-100 and PG-1 induced degranulation in rat basophilic leukemia (RBL-2H3) cells stably expressing Mas related G protein coupled receptor X2 (MrgX2). Chemical synthesis of these AMPs is prohibitively expensive and post-synthesis modifications (cyclization, disulfide bonds, folding) are inadequate for optimal antimicrobial activity. Indeed, we found that synthetic RC-100, which caused mast cell degranulation via MrgX2, did not display any antimicrobial activity. Green-fluorescent protein (GFP)-tagged RC-101 (analog of RC-100) and GFP-tagged PG-1 purified from transgenic plant chloroplasts killed bacteria and induced mast cell degranulation. Furthermore, GFP-PG1 bound specifically to RBL-2H3 cells expressing MrgX2. These findings suggest that retrocyclins and protegrins activate HMCs independently of FPRL1 but via MrgX2. Harnessing this novel feature of AMPs to activate mast cell's host defense/wound healing properties in addition to their antimicrobial activities expands their clinical potential. Low cost production of AMPs in plants should facilitate their advancement to the clinic overcoming major hurdles in current production systems.

  19. What is profound?

    DEFF Research Database (Denmark)

    Sobisch, Jan-Ulrich

    2013-01-01

    Discussing the question, which elements on the path are to be considered profound. While a general view is that the most subtle practises are also the most profound, 'Jig-rten-mgon-po maintains that the most fundamental one's are to be considered the most profound....

  20. Antioxidant and immunomodulatory properties of polysaccharides from Allanblackia floribunda Oliv stem bark and Chromolaena odorata (L.) King and H.E. Robins leaves.

    Science.gov (United States)

    Boudjeko, Thaddée; Megnekou, Rosette; Woguia, Alice Louise; Kegne, Francine Mediesse; Ngomoyogoli, Judith Emery Kanemoto; Tchapoum, Christiane Danielle Nounga; Koum, Olga

    2015-12-09

    Many plant polysaccharides have shown high antioxidant and immunostimulating properties and can be explored as novel molecules with biological properties that can potentially improve immune function. The objective of this work was to characterize soluble and cell wall polysaccharides isolated from the stem bark of Allanblackia floribunda and Chromolaena odorata leaves and to evaluate their antioxidant and immunomodulatory properties. Three polysaccharide fractions: soluble polysaccharides (PoS), pectins (Pec) and hemicelluloses (Hem) were extracted from A. floribunda stem bark and C. odorata leaves. These samples were analysed for their proteins, phenolic compounds and total sugar contents. The monosaccharide composition was determined by gas chromatography and arabinogalactan proteins content in PoS was evaluated by rocket electrophoresis. The in vitro antioxidant activities were evaluated by 1, 1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-bis-3-éthylbenzylthiazoline-6-sulphonic acid (ABTS) radical scavenging assays and ferrous ions chelating activity. Immunomodulatory activities were performed on the peripheral blood mononuclear cells (PBMCs) using proliferation and enzyme linked immunospot (ELISPOT) method to determine the production of an interferon-gamma. The characterization of the various fractions showed varied metabolites in each plant. In PoS fractions, Ara and Gal were the major monosaccharides found, indicating that arabinogalactans are the primary macromolecules. Hem fractions contained predominantly Xyl and GalA for A. floribunda and Xyl (upto 80 %) for and C. odorata. A. floribunda Hem fraction and C. odorata PoS fraction showed significant DPPH and ABTS radical scavenging activities and immunostimulatory activity via stimulation of PBMC and production of IFN-γ in a dose-dependent manner. The results obtained from this study support the ethnomedicinal use of the stem bark of A. floribunda and leaves of C. odorata. Further research is

  1. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

    Directory of Open Access Journals (Sweden)

    Isaac Perea-Gil

    2015-01-01

    Full Text Available Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs. Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells.

  2. Characterization of the therapeutic properties of Chinese herbal materials by measuring delayed luminescence and dendritic cell-based immunomodulatory response

    NARCIS (Netherlands)

    Sun, M.; Chang, W.T.; Wijk, E. van; He, M.; Koval, S.; Lin, M.K.; Van Wijk, R.; Hankemeier, T.; Greef, J. van der; Wang, M.

    2017-01-01

    Based on the traditional Chinese medicine theory, the Chinese pharmacopeia assigns a therapeutic description of “taste” to all herbs; thus, an herb's “taste” is valued in traditional Chinese medicine as a major ethnopharmacological category and reflects the herb's therapeutic properties. These

  3. Immunomodulatory properties of mesenchymal stem cells derived from dental pulp and dental follicle are susceptible to activation by toll-like receptor agonists.

    Science.gov (United States)

    Tomic, Sergej; Djokic, Jelena; Vasilijic, Sasa; Vucevic, Dragana; Todorovic, Vera; Supic, Gordana; Colic, Miodrag

    2011-04-01

    Adult mesenchymal stem cells (MSCs) have recently become a potent tool in regenerative medicine. Due to certain shortcomings of obtaining bone marrow MSCs, alternate sources of MSCs have been sought. In this work, we studied MSCs from dental pulp (DP-MSCs) and dental follicle (DF-MSCs), isolated from the same tooth/donor, to define differences in their phenotypic properties, differentiation potential, and immunomodulatory activities. Both cell types showed colony-forming ability and expressed typical MSCs markers, but differed in the levels of their expression. DF-MSCs proliferated faster, contained cells larger in diameter, exhibited a higher potential to form adipocytes and a lower potential to form chondrocytes and osteoblasts, compared with DP-MSCs. In contrast to DF-MSCs, DP-MSCs produced the transforming growth factor (TGF)-β and suppressed proliferation of peripheral blood mononuclear cells, which could be neutralized with anti-TGF-β antibody. The treatment with toll-like receptor 3 (TLR3) agonist augmented the suppressive potential of both cell types and potentiated TGF-β and interleukin-6 secretions by these cells. TLR4 agonist augmented the suppressive potential of DF-MSCs and increased TGF-β production, but abrogated the immunosuppressive activity of DP-MSCs by inhibiting TGF-β production and the expression of indolamine-2,3-dioxygenase-1. Some of these effects correlated with the higher expression of TLR3 and TLR4 by DP-MSCs compared with DF-MSCs. When transplanted in imunocompetent xenogenic host, both cell types induced formation of granulomatous tissue. In conclusion, our results suggest that dental MSCs are functionally different and each of these functions should be further explored in vivo before their specific biomedical applications.

  4. An in vitro investigation of immunomodulatory properties of Lactobacillus plantarum and L. delbrueckii cells and their extracellular polysaccharides.

    Science.gov (United States)

    Kishimoto, Mana; Nomoto, Ryohei; Mizuno, Masashi; Osawa, Ro

    2017-01-01

    Many probiotic lactobacilli and their extracellular polysaccharides (EPS) have beneficial immunological properties. However, it is unclear how they elicit the host immune response. We thus investigated the immunological properties of UV-killed Lactobacillus delbrueckii TU-1 and L. plantarum KM-9 cells as well as their extracellular polysaccharides (EPSs). High-performance liquid chromatography and ion exchange chromatography analyses showed that their EPSs differ in sugar composition and sugar fractionation. The immunological properties were evaluated in a semi-intestinal model using a Transwell co-culture system that employed human intestinal epithelial (Caco-2) cells on the apical side and murine macrophage (RAW264.7) cells on the basolateral side. The UV-killed cells and EPSs were added to the apical side to allow direct contact with Caco-2 cells and incubated for 6 hr. After incubation, the amounts of tumor necrosis factor-α and several cytokines released by RAW264.7 or Caco-2 cells were quantified by cytotoxic activity on L929 cells (murine fibrosarcoma cell line) and quantitative reverse-transcriptase PCR. We found that the UV-killed cells and their EPSs had immunological effects on RAW264.7 cells via Caco-2 cells. The RAW264.7 cells showed different cytokine production profiles when treated with UV-killed cells and EPSs. The UV-killed cells and EPSs promoted a Th1-type cellular response. Furthermore, we found that the UV-killed cells sent positive signals through Toll-like receptor (TLR) 2. Meanwhile, neither EPS sent a positive signal through TLR4 and TLR2. This evidence suggests that both UV-killed cells of the lactobacillus strains and their EPSs trigger a Th1-type immune response in a human host, with the former triggering the response via the TLRs expressed on its epithelium and the latter employing a mechanism yet to be determined, possibly involving a novel receptor that is designed to recognize specific patterns of repeating sugar in the EPSs.

  5. Biofilms of Lactobacillus plantarum and Lactobacillus fermentum: Effect on stress responses, antagonistic effects on pathogen growth and immunomodulatory properties.

    Science.gov (United States)

    Aoudia, Nabil; Rieu, Aurélie; Briandet, Romain; Deschamps, Julien; Chluba, Johanna; Jego, Gaëtan; Garrido, Carmen; Guzzo, Jean

    2016-02-01

    Few studies have extensively investigated probiotic functions associated with biofilms. Here, we show that strains of Lactobacillus plantarum and Lactobacillus fermentum are able to grow as biofilm on abiotic surfaces, but the biomass density differs between strains. We performed microtiter plate biofilm assays under growth conditions mimicking to the gastrointestinal environment. Osmolarity and low concentrations of bile significantly enhanced Lactobacillus spatial organization. Two L. plantarum strains were able to form biofilms under high concentrations of bile and mucus. We used the agar well-diffusion method to show that supernatants from all Lactobacillus except the NA4 isolate produced food pathogen inhibitory molecules in biofilm. Moreover, TNF-α production by LPS-activated human monocytoid cells was suppressed by supernatants from Lactobacillus cultivated as biofilms but not by planktonic culture supernatants. However, only L. fermentum NA4 showed anti-inflammatory effects in zebrafish embryos fed with probiotic bacteria, as assessed by cytokine transcript level (TNF-α, IL-1β and IL-10). We conclude that the biofilm mode of life is associated with beneficial probiotic properties of lactobacilli, in a strain dependent manner. Those results suggest that characterization of isolate phenotype in the biofilm state could be additional valuable information for the selection of probiotic strains. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Hepatoprotective and immunomodulatory properties of aqueous extract of Curcuma longa in carbon tetra chloride intoxicated Swiss albino mice.

    Science.gov (United States)

    Sengupta, Mahuya; Sharma, Gauri Dutta; Chakraborty, Biswajit

    2011-06-01

    To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl4 intoxicated Swiss albino mice. First group of mice (n=5) received CCl4 treatment at a dose of 0.5 mL/kg bw (i.p.) for 7 days. Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for 15 days. The third group was given both the turmeric extract (for 15 days, orally) and CCl4 (for last 7 days, i.p.). The fourth group was kept as a control. To study the liver function, the transaminase enzymes (SGOT and SGPT) and bilirubin level were measured in the serum of respective groups. For assaying the immunotherapeutic action of Curcuma longa (C. longa), non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups. The result of present study suggested that CCl4 administration increased the level of SGOT and SGPT and bilirubin level in serum. However, the aqueous extract of turmeric reduced the level of SGOT, SGPT and bilirubin in CCl4 intoxicated mice. Apart from damaging the liver system, CCl4 also reduced non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages. Administration of aqueous extract of C. longa offered significant protection from these damaging actions of CCl4 on the non specific host response in the peritoneal macrophages of CCl4 intoxicated mice. In conclusion, the present study suggests that C. longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.

  7. Trehalolipid biosurfactants from nonpathogenic Rhodococcus actinobacteria with diverse immunomodulatory activities.

    Science.gov (United States)

    Kuyukina, Maria S; Ivshina, Irena B; Baeva, Tatiana A; Kochina, Olesia A; Gein, Sergey V; Chereshnev, Valery A

    2015-12-25

    Actinobacteria of the genus Rhodococcus produce trehalolipid biosurfactants with versatile biochemical properties and low toxicity. In recent years, these biosurfactants are increasingly studied as possible biomedical agents with expressed immunological activities. Applications of trehalolipids from Rhodococcus, predominantly cell-bound, in biomedicine are also attractive because their cost drawback could be less significant for high-value products. The review summarizes recent findings in immunomodulatory activities of trehalolipid biosurfactants from nonpathogenic Rhodococcus and related actinobacteria and compares their biomedical potential with well-known immunomodifying properties of trehalose dimycolates from Mycobacterium tuberculosis. Molecular mechanisms of trehalolipid interactions with immunocompetent cells are also discussed. Copyright © 2015. Published by Elsevier B.V.

  8. Attenuation of massive cytokine response to the staphylococcal enterotoxin B superantigen by the innate immunomodulatory protein lactoferrin

    Science.gov (United States)

    Hayworth, J L; Kasper, K J; Leon-Ponte, M; Herfst, C A; Yue, D; Brintnell, W C; Mazzuca, D M; Heinrichs, D E; Cairns, E; Madrenas, J; Hoskin, D W; McCormick, J K; Haeryfar, S M M

    2009-01-01

    Staphylococcal enterotoxin B (SEB) is a pyrogenic exotoxin and a potent superantigen which causes massive T cell activation and cytokine secretion, leading to profound immunosuppression and morbidity. The inhibition of SEB-induced responses is thus considered a goal in the management of certain types of staphylococcal infections. Lactoferrin (LF) is a multi-functional glycoprotein with both bacteriostatic and bactericidal activities. In addition, LF is known to have potent immunomodulatory properties. Given the anti-microbial and anti-inflammatory properties of this protein, we hypothesized that LF can modulate T cell responses to SEB. Here, we report that bovine LF (bLF) was indeed able to attenuate SEB-induced proliferation, interleukin-2 production and CD25 expression by human leucocyte antigen (HLA)-DR4 transgenic mouse T cells. This inhibition was not due to bLF's iron-binding capacity, and could be mimicked by the bLF-derived peptide lactoferricin. Cytokine secretion by an engineered SEB-responsive human Jurkat T cell line and by peripheral blood mononuclear cells from healthy donors was also inhibited by bLF. These findings reveal a previously unrecognized property of LF in modulation of SEB-triggered immune activation and suggest a therapeutic potential for this naturally occurring protein during toxic shock syndrome. PMID:19659771

  9. Immunomodulatory Nature and Site Specific Affinity of Mesenchymal Stem Cells: a Hope in Cell Therapy

    Directory of Open Access Journals (Sweden)

    Parisa Lotfinegad

    2014-03-01

    Full Text Available Immunosuppressive ability of mesenchymal stem cells (MSCs, their differentiation properties to various specialized tissue types, ease of in vitro and in vivo expansion and specific migration capacity, make them to be tested in different clinical trials for the treatment of various diseases. The immunomodulatory effects of MSCs are less identified which probably has high clinically significance. The clinical trials based on primary research will cause better understanding the ability of MSCs in immunomodulatory applications and site specific migration in the optimization of therapy. So, this review focus on MSCs functional role in modulating immune responses, their ability in homing to tumor, their potency as delivery vehicle and their medical importance.

  10. Immunomodulatory Nature and Site Specific Affinity of Mesenchymal Stem Cells: a Hope in Cell Therapy

    Science.gov (United States)

    Lotfinegad, Parisa; Shamsasenjan, karim; Movassaghpour, Aliakbar; Majidi, Jafar; Baradaran, Behzad

    2014-01-01

    Immunosuppressive ability of mesenchymal stem cells (MSCs), their differentiation properties to various specialized tissue types, ease of in vitro and in vivo expansion and specific migration capacity, make them to be tested in different clinical trials for the treatment of various diseases. The immunomodulatory effects of MSCs are less identified which probably has high clinically significance. The clinical trials based on primary research will cause better understanding the ability of MSCs in immunomodulatory applications and site specific migration in the optimization of therapy. So, this review focus on MSCs functional role in modulating immune responses, their ability in homing to tumor, their potency as delivery vehicle and their medical importance. PMID:24409403

  11. Immunomodulatory Potential of Patchouli Alcohol Isolated from ...

    African Journals Online (AJOL)

    Purpose: To isolate and purify patchouli alcohol (PA), a tricyclic sesquiterpene constituent of Pogostemon cablin, and investigate its immunomodulatory potential in Kunming mice. Methods: PA was prepared from an ethanol aqueous extract of P. cablin by silica gel column chromatography, and further purified by ...

  12. Parasitic helminths and HIV-1 infection: the effect of immunomodulatory antigens

    NARCIS (Netherlands)

    Mouser, E.E.I.M.

    2016-01-01

    In many regions of the world co-infection with parasitic helminths and HIV-1 is common. Both pathogens have major implications for the host immune system, helminths possess immunomodulatory properties whilst HIV-1 infects and kills immune cells. Currently very little is known regarding what effects

  13. Anti-inflammatory and immunomodulatory effects of antibiotics and their use in dermatology

    OpenAIRE

    Swetalina Pradhan; Bhushan Madke; Poonam Kabra; Adarsh Lata Singh

    2016-01-01

    Antibiotics (antibacterial, antiviral, and antiparasitic) are class of drugs which result in either killing or inhibiting growth and multiplication of infectious organisms. Antibiotics are commonly prescribed by all specialties for treatment of infections. However, antibiotics have hitherto immunomodulatory and anti-inflammatory properties and can be exploited for various noninfectious dermatoses. Dermatologists routinely prescribe antibiotics in treatment of various noninfectious disorders. ...

  14. Achieving profound anesthesia using the intraosseous technique.

    Science.gov (United States)

    Coury, K A

    1997-10-01

    The intraosseous technique has been described as a useful adjunct to primary anesthetic administration. It has several advantages (Table 3) over other supplemental techniques in that it is relatively simple to implement into routine practice, it affords fast, predictable results, and it is relatively painless. The technique has been shown to be very successful in achieving profound pulpal anesthesia when administered as a supplement to the inferior alveolar nerve block and is effective in achieving profound anesthesia in irreversibly inflamed teeth, especially mandibular molars.

  15. Antitumor and immunomodulatory activity of Inonotus obliquus

    Directory of Open Access Journals (Sweden)

    Staniszewska Justyna

    2017-06-01

    Full Text Available The article presents the antitumor and immunomodulatory activity of compounds and extracts from Inonotus obliquus. Polysaccharides isolated from sclerotium have a direct antitumor effect due to protein synthesis inhibition in tumor cells. Polysaccharides derived from the mycelium function by activating the immune system. Due to the limited toxicity of these substances, both extracts as well as isolated and purified chemicals may be a good alternative to current chemotherapy and play a role in cancer prevention. In vitro experiments have shown the inhibition of inflammation with the influence of action of I. obliquus extracts; however, in vivo experiments on animals implanted with tumor cells of different types have shown the activation of the host immune system. This led to decrease in tumor mass and prolonged survival. The immunomodulatory mechanism of action is complex and it seems that stimulation of macrophages and induction of apoptosis in cancer cells is of great importance.

  16. Signal processing for the profoundly deaf.

    Science.gov (United States)

    Boothyroyd, A

    1990-01-01

    Profound deafness, defined here as a hearing loss in excess of 90 dB, is characterized by high thresholds, reduced hearing range in the intensity and frequency domains, and poor resolution in the frequency and time domains. The high thresholds call for hearing aids with unusually high gains or remote microphones that can be placed close to the signal source. The former option creates acoustic feedback problems for which digital signal processing may yet offer solutions. The latter option calls for carrier wave technology that is already available. The reduced frequency and intensity ranges would appear to call for frequency and/or amplitude compression. It might also be argued, however, that any attempts to compress the acoustic signal into the limited hearing range of the profoundly deaf will be counterproductive because of poor frequency and time resolution, especially when the signal is present in noise. In experiments with a 2-channel compression system, only 1 of 9 subjects showed an improvement of perception with the introduction of fast-release (20 ms) compression. The other 8 experienced no benefit or a slight deterioration of performance. These results support the concept of providing the profoundly deaf with simpler, rather than more complex, patterns, perhaps through the use of feature extraction hearing aids. Data from users of cochlear implants already employing feature extraction techniques also support this concept.

  17. Induction of cellular and molecular immunomodulatory pathways by vitamin A and Flavonoids

    Science.gov (United States)

    Patel, Sapna; Vajdy, Michael

    2016-01-01

    Introduction A detailed study of reports on the immunomodulatory properties of vitamin A and select flavonoids may pave the way for using these natural compounds or compounds with similar structures in novel drug and vaccine designs against infectious and autoimmune diseases and cancers. Areas Covered Intracellular transduction pathways, cellular differentiation and functional immunomodulatory responses have been reviewed. The reported studies encompass in vitro, in vivo preclinical and clinical studies that address the role of Vitamin A and select flavonoids in induction of innate and adaptive B and T cell responses, including TH1, TH2 and Treg. Expert Opinion While the immunomodulatory role of vitamin A, and related compounds, is well-established in many preclinical studies, its role in humans has begun to gain wider acceptance. In contrast, the role of flavonoids is mostly controversial in clinical trials, due to the diversity of the various classes of these compounds, and possibly due to the purity and the selected doses of the compounds. However, current preclinical and clinical studies warrant further detailed studies of these promising immuno-modulatory compounds. PMID:26185959

  18. Immunomodulatory effects of aqueous and organic fractions from Petiveria alliacea on human dendritic cells.

    Science.gov (United States)

    Santander, Sandra Paola; Hernández, John Fredy; Barreto, Claudia Cifuentes; Cifuentes B, Claudia; Masayuki, Aoki; M, Aoki; Moins-Teisserenc, Hélène; H, Moins-Teisserenc; Fiorentino, Susana

    2012-01-01

    Petiveria alliacea is a plant traditionally known for its anti-inflammatory and anti-tumor activities; however, the molecular and cellular mechanisms of its immunomodulatory properties are still unknown. Dendritic cells (DC) promote adaptive immune response by activating T lymphocytes, inducing an effector response or tolerance depending on the DC differentiation level. Herein, we evaluated the immunomodulatory activity of aqueous and organic plant fractions from P. alliacea using human monocyte-derived dendritic cells. The phenotype, cytokine secretion and gene expression were estimated after treatment with the plant fractions. We found that P. alliacea aqueous fraction induced morphological changes and co-stimulatory expression of CD86, indicating partial DC maturation. In addition, pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF-α were secreted. The fraction also increased NF-κB gene expression while down-regulating TGFβ gene expression. These results suggest that the aqueous fraction can induce partial DC activation, a situation that can be relevant in tolerance induction. It is important to state that the organic fraction by itself does not show any immunomodulatory activity. This study provides evidence for possible immunomodulatory activity of P. alliacea extracts which has been used in traditional medicine in Colombia.

  19. Profound bradycardia associated with NIV removal.

    Science.gov (United States)

    Echevarria, C; Bourke, S C; Gibson, G J

    2012-01-01

    A patient with lower-limb onset ALS presented with a one-month history of vasovagal episodes and a one-week history of cough productive of green sputum and lethargy. She was drowsy and in acute on chronic type-two respiratory failure. She responded to non-invasive ventilation, however she suffered recurrent episodes of profound bradycardia on removal of the mask, which gradually resolved over ten days. We have reviewed the literature and offer a potential explanation for these events.

  20. Asystole Following Profound Vagal Stimulation During Hepatectomy

    Directory of Open Access Journals (Sweden)

    Preeta John

    2008-01-01

    Full Text Available Asystole in a non laparoscopic upper abdominal surgery following intense vagal stimulation is a rare event. This case report highlights the need for awareness of such a complication when a thoracic epidural anaesthetic has been given in addition to a general anaesthetic for an upper abdominal procedure. A combined thoracic epidural and general anaesthetic was given. The anterior abdominal wall was retracted forty minutes after administration of the epidural bolus. This maneuver resulted in a profound vagal response with bradycardia and asystole. The patient was resuscitated successfully with a cardiac massage, atropine and adrenaline and the surgery was resumed. Surgery lasted eleven hours and was uneventful.

  1. Assessment of immunomodulatory activity of aqueous extract of Calamus rotang

    Directory of Open Access Journals (Sweden)

    Amit Gupta

    2017-04-01

    Full Text Available Objective: There are a number of medicinal plant products which has been used to treat various immunological diseases. Out of these medicinal plants, Calamus rotang has shown several medicinal properties including anti-viral, anti-diabetic, anti-inflammatory effects. Normally, the roots of C. rotang are used in various ailments to cure piles, burning sensation, cough, leprosy and bleeding disorder and also it was used in the treatment of inflammation. In the present study, our group were investigated the immunomodulatory activity of aqueous extract of C. rotang root in human whole blood and peripheral blood mononuclear cells (PBMC using hepatitis B vaccine (HBsAg as an antigen. Materials and Methods: Variable doses of root aqueous extract (0.5 – 30 mg/ml, 100 µl was administered to human whole blood and PBMC using hepatitis B vaccine containing surface antigen (HBsAg; 20 µg/ml, 10 µl as specific antigen in order to estimate the total blood counts in human whole blood and nitric oxide production and CD14 FITC surface marker from human PBMC. Results: Overall, the results showed that roots aqueous extract of C. rotang showed remarkable increase in the number of blood counts in human whole blood at lower doses (0.5 mg/ml. In addition, root aqueous extract of C. rotang also showed the same pattern in case of nitric oxide production and estimation of CD14 FITC surface marker in human PBMC. Conclusion: Altogether, the results suggest that root aqueous extract of C. rotang showed immunomodulatory activity.

  2. Novel immunomodulatory effects of adiponectin on dendritic cell functions.

    Science.gov (United States)

    Tsang, Julia Yuen Shan; Li, Daxu; Ho, Derek; Peng, Jiao; Xu, Aimin; Lamb, Jonathan; Chen, Yan; Tam, Paul Kwong Hang

    2011-05-01

    Adiponectin (ADN) is an adipocytokine with anti-inflammatory properties. Although it has been reported that ADN can inhibit the immunostimulatory function of monocytes and macrophages, little is known of its effect on dendritic cells (DC). Recent data suggest that ADN can regulate immune responses. DCs are uniquely specialised antigen presenting cells that play a central role in the initiation of immunity and tolerance. In this study, we have investigated the immuno- modulatory effects of ADN on DC functions. We found that ADN has only moderate effect on the differentiation of murine bone marrow (BM) derived DCs but altered the phenotype of DCs. The expression of major histocompatibilty complex class II (MHCII), CD80 and CD86 on ADN conditioned DCs (ADN-DCs) was lower than that on untreated cells. The production of IL-12p40 was also suppressed in ADN-DCs. Interestingly, ADN treated DCs showed an increase in the expression of the inhibitory molecule, programmed death-1 ligand (PDL-1) compared to untreated cells. In vitro co-culture of ADN-DCs with allogeneic T cells led to a decrease in T cell proliferation and reduction of IL-2 production. Concomitant with that, a higher percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) was detected in co-cultures of T cells and ADN-DCs. Blocking PD-1/PDL-1 pathway could partially restore T cell function. These findings suggest that the immunomodulatory effect of ADN on immune responses could be at least partially be mediated by its ability to alter DC function. The PD-1/PDL-1 pathway and the enhancement of Treg expansion are implicated in the immunomodulatory mechanisms. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Immunomodulatory effects of histone deacetylase inhibitors.

    Science.gov (United States)

    Licciardi, P V; Ververis, K; Tang, M L; El-Osta, A; Karagiannis, T C

    2013-05-01

    Histone deacetylase inhibitors (HDACi) have emerged as a new generation of anticancer therapeutics. The classical broad-spectrum HDACi typically alter the cell cycle distribution and induce cell death, apoptosis and differentiation in malignant and transformed cells. This provides the basis for the clinical potential of HDACi in cancer therapy. Currently two compounds, suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza™) and depsipeptide (Romidepsin, Istodax™) have been approved for by the US Food and Drug Administration for the treatment of refractory cutaneous T-cell lymphoma. Apart from clinical application in oncology, HDACi have also been investigated as potential therapeutics for various pathologies including those of the central nervous system (such as Huntington's disease and multiple sclerosis), cardiac conditions (particularly hypertrophy), arthritis and malaria. Further, evidence is accumulating for potent immunomodulatory effects of classical HDACi which is the focus of this review. We review the antiinflammatory effects of HDACi and in particular findings implicating regulation of the innate and adaptive immune systems by HDAC enzymes. The recent findings highlighting the immunomodulatory function of HDAC11 which relates to balancing immune activation versus tolerance are also discussed.

  4. Ulcer: An Antioxidative Trail Weaved with Immunomodulatory Effect

    Directory of Open Access Journals (Sweden)

    Ananya Chatterjee

    2011-01-01

    Full Text Available Amla (Phyllanthus emblica L., apart from its food value, can be used as a gastroprotective agent in non steroidal anti-inflammatory drug (NSAID-induced gastropathy. It has been suggested that the antioxidative property of amla is the key to its therapeutic effect. Hence, on the basis of in vitro antioxidative potential, the ethanolic extract of amla (eAE was selected for in vivo study in NSAID-induced ulcer. Intriguingly, eAE showed biphasic activity in ulcerated mice, with healing effect observed at 60 mg/kg and an adverse effect at 120 mg/kg.The dose-dependent study revealed that switching from anti-oxidant to pro-oxidant shift and immunomodulatory property could be the major cause for its biphasic effect, as evident from the total antioxidant status, thiol concentration, lipid peroxidation, protein carbonyl content followed by mucin content, PGE2 synthesis and cytokine status. Further, Buthionine sulfoxamine (BSO pretreatment established the potential impact of antioxidative property in the healing action of eAE. However, eAE efficiently reduced pro-inflammatory cytokine (TNF- and IL-1 levels and appreciably upregulate anti-inflammatory cytokine (IL-10 concentration. In conclusion, gastric ulcer healing induced by eAE was driven in a dose-specific manner through the harmonization of the antioxidative property and modulation of anti-inflammatory cytokine level.

  5. Immunomodulatory Nature and Site Specific Affinity of Mesenchymal Stem Cells: a Hope in Cell Therapy

    OpenAIRE

    Lotfinegad, Parisa; Shamsasenjan, karim; Movassaghpour, Aliakbar; Majidi, Jafar; Baradaran, Behzad

    2013-01-01

    Immunosuppressive ability of mesenchymal stem cells (MSCs), their differentiation properties to various specialized tissue types, ease of in vitro and in vivo expansion and specific migration capacity, make them to be tested in different clinical trials for the treatment of various diseases. The immunomodulatory effects of MSCs are less identified which probably has high clinically significance. The clinical trials based on primary research will cause better understanding the ability of MSCs ...

  6. Anti-inflammatory and immunomodulatory mechanisms of atorvastatin in a murine model of traumatic brain injury.

    Science.gov (United States)

    Xu, Xin; Gao, Weiwei; Cheng, Shiqi; Yin, Dongpei; Li, Fei; Wu, Yingang; Sun, Dongdong; Zhou, Shuai; Wang, Dong; Zhang, Yongqiang; Jiang, Rongcai; Zhang, Jianning

    2017-08-23

    Neuroinflammation is an important secondary injury mechanism that has dual beneficial and detrimental roles in the pathophysiology of traumatic brain injury (TBI). Compelling data indicate that statins, a group of lipid-lowering drugs, also have extensive immunomodulatory and anti-inflammatory properties. Among statins, atorvastatin has been demonstrated as a neuroprotective agent in experimental TBI; however, there is a lack of evidence regarding its effects on neuroinflammation during the acute phase of TBI. The current study aimed to evaluate the effects of atorvastatin therapy on modulating the immune reaction, and to explore the possible involvement of peripheral leukocyte invasion and microglia/macrophage polarization in the acute period post-TBI. C57BL/6 mice were subjected to TBI using a controlled cortical impact (CCI) device. Either atorvastatin or vehicle saline was administered orally starting 1 h post-TBI for three consecutive days. Short-term neurological deficits were evaluated using the modified neurological severity score (mNSS) and Rota-rod. Brain-invading leukocyte subpopulations were analyzed by flow cytometry and immunohistochemistry. Pro- and anti-inflammatory cytokines and chemokines were examined using enzyme-linked immunosorbent assay (ELISA). Markers of classically activated (M1) and alternatively activated (M2) microglia/macrophages were then determined by quantitative real-time PCR (qRT-PCR) and flow cytometry. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) staining and immunofluorescence labeling for neuronal nuclei (NeuN). Acute treatment with atorvastatin at doses of 1 mg/kg/day significantly reduced neuronal apoptosis and improved behavioral deficits. Invasions of T cells, neutrophils and natural killer (NK) cells were attenuated profoundly after atorvastatin therapy, as was the production of pro-inflammatory cytokines (IFN-γ and IL-6) and chemokines

  7. The immunomodulatory effects of laparoscopic surgery.

    LENUS (Irish Health Repository)

    Corrigan, Mark

    2012-02-03

    Laparoscopic alternatives to conventional surgical procedures confer many advantages to patients including reduced postoperative pain, shortened convalescence and, perhaps, improved disease-related outcomes. The diminished degree of immune dysfunction apparent with these techniques may underpin these beneficial aspects. However, minimal access is accompanied by various ancillary anesthetic and mechanical associations (including the induction of a carbon dioxide pneumoperitoneum), which must be considered in addition to reduced tissue trauma when attempting to correlate cause with effect. Furthermore, the opportunity to establish causation between the immunomodulatory aspects of laparoscopy and subsequent clinical outcome by prospective, randomized study is difficult because of the rapid incorporation of minimal access techniques into clinical practice. Therefore, experimental in vitro and in vivo studies must be used to complement the limitations of clinical studies in this area. Although the initial investigations into the immunological effects of laparoscopy are encouraging, many of the intricacies associated with this approach still await elaboration.

  8. Therapeutic Potential of HDPs as Immunomodulatory Agents

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Hancock, Robert E.W.

    2010-01-01

    One of the most significant advances in medical history is the discovery and development of antibiotics, which in the middle of last century was flourishing and appeared to be the ultimate solution to the treatment of life-threatening human bacterial diseases. However, lately there has been a huge...... decline in the rate of discovery of new antimicrobial intervention strategies in parallel with an increasing incidence of multidrug-resistant pathogens; if these circumstances do not change we will continue to approach the end of the antibiotic era. Facing this dark future, scientists are considering new...... strategies for intervention tailored around the appropriate (selective) stimulation of the host’s immune system, and particularly rapid acting innate immunity, as an alternative to direct targeting of microbial pathogens. One recent player in such an immunomodulatory strategy is the naturally occurring host...

  9. The role of formyl peptide receptors for immunomodulatory activities of antimicrobial peptides and peptidomimetics

    DEFF Research Database (Denmark)

    Skovbakke, Sarah Line; Holdfeldt, André; Forsman, Huamei

    2018-01-01

    In recent years, the therapeutic potential of antimicrobial peptides (AMPs) as immunomodulators has become generally accepted. Nevertheless, only very few AMP-based compounds have progressed into clinical trials. This paradox may be explained by the fact, that some of the intrinsic properties...... displaying analogous immunomodulatory activity profiles. Neutrophils play key roles in host defense as major effector cells in clearance of pathogens by phagocytosis and by regulating other processes of innate immunity as well as promotion of resolution of inflammation. Several aspects of these effects...... are correlated to their expression of formyl peptide receptors (FPRs) that have been shown to be targets of both natural and synthetic antimicrobial peptides. In the present review recent findings highlighting the role of FPRs in mediating immunomodulatory activities of natural and synthetic AMPs as well...

  10. Isolation, structural elucidation and immunomodulatory activity of fructans from aged garlic extract.

    Science.gov (United States)

    Chandrashekar, Puthanapura M; Prashanth, Keelara V Harish; Venkatesh, Yeldur P

    2011-02-01

    Traditionally, garlic (Allium sativum) is known to be a significant immune booster. Aged garlic extract (AGE) possesses superior immunomodulatory effects than raw garlic; these effects are attributed to the transformed organosulfur compounds. AGE is also known to contain fructans; the amount of fructans in AGE represents a small fraction (0.22%) of the total fructans in raw garlic. In order to evaluate the biological activity of fructans present in AGE, both high molecular weight (>3.5 kDa; HF) and low molecular weight (immunomodulators such as zymosan and mannan. This study clearly demonstrates that garlic fructans also contribute to the immunomodulatory properties of AGE, and is the first such study on the biological effects of garlic fructans. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Sweet whey as a raw material for the dietary supplements obtaining with immunomodulatory effect

    Directory of Open Access Journals (Sweden)

    G. Didukh

    2017-06-01

    Full Text Available This article presents the results of the study of literary sources to prove the viability of the idea of using sweet whey to deep its fractionation, and to obtain biologically active proteins with immunomodulatory effect. We demonstrated methods for fractionation of milk whey (membrane and chromatographic, as well as the technological scheme of concentration of sweet whey. We introduced the composition of sweet whey and protein content of immunomodulatory action. Modern methods of processing whey, which include, basically, only the process of dehydration and concentration of whey and its use in the complete component composition, which limits its use for food purposes are shown. The necessity of processing of secondary resources in a catastrophic ecological situation on the planet and full use of the composite processing of raw materials for food purposes, and also shows properties of proteins immunomodulating actions which are part of the whey are grounded.

  12. Intestinal Immunomodulatory Cells (T Lymphocytes: A Bridge between Gut Microbiota and Diabetes

    Directory of Open Access Journals (Sweden)

    Qingwei Li

    2018-01-01

    Full Text Available Diabetes mellitus (DM is one of the most familiar chronic diseases threatening human health. Recent studies have shown that the development of diabetes is closely related to an imbalance of the gut microbiota. Accordingly, there is increasing interest in how changes in the gut microbiota affect diabetes and its underlying mechanisms. Immunomodulatory cells play important roles in maintaining the normal functioning of the human immune system and in maintaining homeostasis. Intestinal immunomodulatory cells (IICs are located in the intestinal mucosa and are regarded as an intermediary by which the gut microbiota affects physiological and pathological properties. Diabetes can be regulated by IICs, which act as a bridge linking the gut microbiota and DM. Understanding this bridge role of IICs may clarify the mechanisms by which the gut microbiota contributes to DM. Based on recent research, we summarize this process, thereby providing a basis for further studies of diabetes and other similar immune-related diseases.

  13. The Immunomodulatory Effects of Macrolides—A Systematic Review of the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Petra Zimmermann

    2018-03-01

    Full Text Available BackgroundThe mechanisms underlying the non-antimicrobial immunomodulatory properties of macrolides are not well understood.ObjectivesTo systematically review the evidence for the immunomodulatory properties of macrolides in humans and to describe the underlying mechanism and extent of their influence on the innate and adaptive immune system.MethodsA systematic literature search was done in MEDLINE using the OVID interface from 1946 to December 2016 according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA. Original articles investigating the influence of four macrolides (azithromycin, clarithromycin, erythromycin, and roxithromycin on immunological markers in humans were included.ResultsWe identified 22 randomized, controlled trials, 16 prospective cohort studies, and 8 case–control studies investigating 47 different immunological markers (186 measurements in 1,834 participants. The most frequently reported outcomes were a decrease in the number of neutrophils, and the concentrations of neutrophil elastase, interleukin (IL-8, IL-6, IL-1beta, tumor necrosis factor (TNF-alpha, eosinophilic cationic protein, and matrix metalloproteinase 9. Inhibition of neutrophil function was reported more frequently than eosinophil function. A decrease in T helper (Th 2 cells cytokines (IL-4, IL-5, IL-6 was reported more frequently than a decrease in Th1 cytokines (IL-2, INF-gamma.ConclusionMacrolides influence a broad range of immunological mechanisms resulting in immunomodulatory effects. To optimize the treatment of chronic inflammatory diseases by macrolides, further studies are necessary, particularly comparing different macrolides and dose effect relationships.

  14. Profound Understanding of Effect of Transition Metal Dopant, Sintering Temperature, and pO2 on the Electrical and Optical Properties of Proton Conducting BaCe0.9Sm0.1O3-δ.

    Science.gov (United States)

    Handal, Hala T; Hassan, Azfar; Leeson, Ryan; Eloui, Sherif M; Fitzpatrick, Martin; Thangadurai, Venkataraman

    2016-01-19

    This study reports the effect of transition metal (TM) substitution on the electrical and optical properties of BaCe0.9Sm0.1O3-δ (BCS). Concentrations of 5-10 mol % of each of Fe and Co have been doped for the B-site of BCS by citric acid autocombustion method. Powder X-ray diffraction has revealed the formation of an orthorhombic perovskite-type structure. FTIR confirmed a distortion in the lattice upon TM-doping in BCS. Scanning electron microscopy (SEM) images of 1400 °C sintered samples have manifested a higher densification in BaCe0.8Sm0.1Co0.1O3-δ (BCSC10) with a grain size ∼11 μm compared to the parent compound BCS (∼2 μm). Thermogravimetric (TG) analysis showed a water uptake in case of BaCe0.85Sm0.1Co0.05O3-δ (BCSC5), while BaCe0.85Sm0.1Fe0.05O3-δ (BCSF5) did not show a noteworthy uptake of water. TG has also proved that the incorporation of Fe and Co in BCS did not improve the chemical stability in CO2 at elevated temperature. The band gap estimated using Kubelka-Munk model based on the diffuse reflectance data was found to be the lowest for BCSC5 (2.47 eV). However, it increases upon lowering oxygen partial pressure (pO2), which was interpreted by a band structure modifications. Among the samples investigated, BCSC10 sintered at 1400 °C showed the highest electrical conductivity of 0.02 S cm(-1) in air at 600 °C, while its proton mobility appears to be negligible under the investigated humidity atmosphere.

  15. Immunomodulatory Activity of Alcohol Extract of Terminalia chebula ...

    African Journals Online (AJOL)

    Erah

    2011-01-02

    Jan 2, 2011 ... Purpose: To investigate the immunomodulatory activity of the alcohol extract of Terminalia chebula Retz. (Combretaceae) ..... indicates a higher secretion of melatonin. (Mol. Wt. 248 ... especially the immune, nervous, and.

  16. Staffs' documentation of participation for adults with profound intellectual disability or profound intellectual and multiple disabilities.

    Science.gov (United States)

    Talman, Lena; Gustafsson, Christine; Stier, Jonas; Wilder, Jenny

    2017-06-21

    This study investigated what areas of International Classification of Functioning, Disability and Health were documented in implementation plans for adults with profound intellectual disability or profound intellectual and multiple disabilities with focus on participation. A document analysis of 17 implementation plans was performed and International Classification of Functioning, Disability and Health was used as an analytic tool. One hundred and sixty-three different codes were identified, especially in the components Activities and participation and Environmental factors. Participation was most frequently coded in the chapters Community, social and civic life and Self-care. Overall, the results showed that focus in the implementation plans concerned Self-care and Community, social and civic life. The other life areas in Activities and participation were seldom, or not at all, documented. A deeper focus on participation in the implementation plans and all life areas in the component Activities and participation is needed. It is important that the documentation clearly shows what the adult wants, wishes, and likes in everyday life. It is also important to ensure that the job description for staff contains both life areas and individual preferences so that staff have the possibility to work to fulfill social and individual participation for the target group. Implications for rehabilitation There is a need for functioning working models to increase participation significantly for adults with profound intellectual disability or profound intellectual and multiple disabilities. For these adults, participation is achieved through the assistance of others and support and services carried out must be documented in an implementation plan. The International Classification of Functioning, Disability and Health can be used to support staff and ensure that information about the most important factors in an individual's functioning in their environment is not omitted in

  17. Antibacterial, Antiproliferative, and Immunomodulatory Activity of Silver Nanoparticles Synthesized with Fucans from the Alga Dictyota mertensii

    Directory of Open Access Journals (Sweden)

    Marília Medeiros Fernandes-Negreiros

    2017-12-01

    Full Text Available In this study, we aimed to synthesize silver nanoparticles containing fucans from Dictyota mertensii (Martius Kützing using an environmentally friendly method and to characterize their structure as well as antiproliferative, immunomodulatory, and antibacterial effects. Fucan-coated silver nanoparticles (FN were characterized by Fourier-transform infrared analysis, dynamic light scattering, zeta potential, atomic force microscopy, energy dispersive X-ray spectroscopy, and inductively coupled plasma emission spectrometry. They were evaluated for their effect on cell viability, minimum inhibitory bactericidal concentration, and release of nitric oxide and cytokines. The FN were successfully synthesized using an environmentally friendly method. They were size-stable for 16 months, of a spherical shape, negative charge (−19.1 mV, and an average size of 103.3 ± 43 nm. They were able to inhibit the proliferation of the melanoma tumor cell line B16F10 (60%. In addition, they had immunomodulatory properties: they caused an up to 7000-fold increase in the release of nitric oxide and cytokines (IL-10; IL-6 and TNF-α up to 7000 times. In addition, the FN showed inhibitory effect on Gram-positive and -negative bacteria, with MIC values of 50 µg/mL. Overall, the data showed that FN are nanoparticles with the potential to be used as antitumor, immunomodulatory, and antibacterial agents.

  18. Endocrine disrupting activities and immunomodulatory effects in lymphoblastoid cell lines of diclofenac, 4-hydroxydiclofenac and paracetamol.

    Science.gov (United States)

    Klopčič, Ivana; Markovič, Tijana; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner

    2018-05-16

    A critical literature review reveals that knowledge of side effects of pharmaceuticals diclofenac and paracetamol is extremely important because of their widespread use and occurrence in the environment. In order to delineate whether these compounds have endocrine activity and influence on the immune system, we assessed the potential endocrine disrupting and immunomodulatory activities of: diclofenac (DIC), its metabolite 4-hydroxydiclofenac (4-HD) and paracetamol (PAR). Herein, we report on their impact on estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR) and thyroid hormone receptor (TR). The endocrine disrupting effects were assessed in vitro in MDA-kb2 and GH3.TRE-Luc cell lines and by the XenoScreen YES/YAS assay. Moreover, binding affinity to nuclear receptors (GR and AR) was also measured. Immunomodulatory properties of the compounds were evaluated in lymphoblastoid cell lines. All the tested compounds showed endocrine disrupting and immunomodulatory activities. The results revealed that both DIC and its metabolite 4-HD exhibited significant estrogenic, anti-androgenic (in YAS assay), (anti)-androgenic, (anti)-glucocorticoid and anti-thyroid hormonal activities (in luciferase reporter gene assays). DIC showed direct binding to the GR, while its metabolite 4-HD to the GR and AR. Only metabolite 4-HD showed estrogenic, androgenic (in YAS assay) and thyroid-hormonal activities. PAR had anti-androgenic activity and anti-thyroid hormonal activity. PAR displayed GR agonist activity with competition to its receptor and agonistic activity to AR. All of the compounds significantly modulated pro-inflammatory and immunoregulatory cytokine production in lymphoblastoid cell lines and were thus proven immunomodulatory. The study is useful in determining toxicological effects and contributes to the knowledge of possible side effects of diclofenac, its metabolite and paracetamol. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Immunomodulatory effect of Mesenchymal Stem Cells on B cells

    Directory of Open Access Journals (Sweden)

    Marcella eFranquesa

    2012-07-01

    Full Text Available The research on T cell immunosuppression therapies has attracted most of the attention in clinical transplantation. However, B cells and humoral immune responses are increasingly acknowledged as crucial mediators of chronic allograft rejection. Indeed, humoral immune responses can lead to renal allograft rejection even in patients whose cell-mediated immune responses are well controlled. On the other hand, newly studied B cell subsets with regulatory effects have been linked to tolerance achievement in transplantation. Better understanding of the regulatory and effector B cell responses may therefore lead to new therapeutic approaches.Mesenchymal Stem Cells (MSC are arising as a potent therapeutic tool in transplantation due to their regenerative and immunomodulatory properties. The research on MSCs has mainly focused on their effects on T cells and although data regarding the modulatory effects of MSCs on alloantigen-specific humoral response in humans is scarce, it has been demonstrated that MSCs significantly affect B cell functioning. In the present review we will analyze and discuss the results in this field.

  20. Immunomodulatory effect of diethylcarbamazine in mice infected with Nocardia brasiliensis.

    Science.gov (United States)

    García-Hernández, M; Castro-Corona, M A; Segoviano-Ramírez, J C; Brattig, N W; Medina-De la Garza, C E

    2014-11-01

    We tested whether diethylcarbamazine (DEC) or ivermectin (IVM), both antiparasitic drugs with reported immunomodulatory properties, were able to affect the immune system to potentiate host defense mechanisms and protect against actinomycetoma in a mouse model. Male BALB/c mice of 10-12 weeks of age were injected with either Nocardia brasiliensis or saline solution. Recorded were the effects of a treatment by DEC (6 mg/kg per os daily for one week) or IVM (200 μg/kg subcutaneously on days 1 and 3) on (i) the development of mycetoma lesion, (ii) the expression of reactive oxygen intermediates (ROI) by phagocytes, (iii) the proliferation index of lymphocytes and (iv) antibody production of IgG and IgM. After an initial lesion in all mice, DEC inhibited a full development and progression of actinomycetoma resulting in a reduced lesion size (p brasiliensis antigens and concanavalin A in DEC-treated group was higher than in non-treated group at day 21 and 28 postinfection (p brasiliensis leading to retrogression of the mycetoma and increasing cellular immune responses. Our findings may indicate a potential use of DEC as a putative adjuvant in infectious disease or vaccination. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. The immunomodulatory effects of titanium dioxide and silver nanoparticles.

    Science.gov (United States)

    Lappas, Courtney M

    2015-11-01

    Due to their characteristic physical, chemical and optical properties, titanium dioxide and silver nanoparticles are attractive tools for use in a wide range of applications. The use of nanoparticles for biological applications is, however, dependent upon their biocompatibility with living cells. Because of the importance of inflammation as a modulator of human health, the safe and efficacious in vivo use of titanium dioxide and silver nanoparticles is inherently linked to a favorable interaction with immune system cells. However, both titanium dioxide and silver nanoparticles have demonstrated potential to exert immunomodulatory and immunotoxic effects. Titanium dioxide and silver nanoparticles are readily internalized by immune system cells, may accumulate in peripheral lymphoid organs, and can influence multiple manifestations of immune cell activity. Although the factors influencing the biocompatibility of titanium dioxide and silver nanoparticles with immune system cells have not been fully elucidated, nanoparticle core composition, size, concentration and the duration of cell exposure seem to be important. Because titanium dioxide and silver nanoparticles are widely utilized in pharmaceutical, commercial and industrial products, it is vital that their effects on human health and immune system function be more thoroughly evaluated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma

    OpenAIRE

    Arancibia, Sergio; Espinoza, Cecilia; Salazar, Fabián; Del Campo, Miguel; Tampe, Ricardo; Zhong, Ta-Ying; De Ioannes, Pablo; Moltedo, Bruno; Ferreira, Jorge; Lavelle, Ed C.; Manubens, Augusto; De Ioannes, Alfredo E.; Becker, María Inés

    2014-01-01

    PUBLISHED Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treatment of cancer. In this study, we evaluated a novel hemocyanin from the limpet/gastropo...

  3. The influence of protein malnutrition on biological and immunomodulatory aspects of bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Dos Santos, Guilherme Galvão; Batool, Shafqat; Hastreiter, Araceli; Sartori, Talita; Nogueira-Pedro, Amanda; Borelli, Primavera; Fock, Ricardo Ambrosio

    2017-08-01

    Tissues that require a great supply of nutrients and possess high metabolic demands, such as lympho-hemopoietics tissues, are the first to be affected by protein malnutrition (PM). Thus, PM directly affects hemopoiesis and the production and function of immune cells. Consequently, malnourished individuals are more susceptible to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are important in the formation of lympho-hemopoietic stroma. Since an adequate supply of nutrients is essential to sustain stroma formation, which is mainly constituted of MSCs and differentiated cells originated from them, this study investigated whether PM would influence some biological and immunomodulatory aspects of MSCs. Two-month-old Balb/c mice were divided into control and malnourished groups receiving normoproteic or hypoproteic diets, respectively (12% and 2% of protein) for 28 days. MSCs obtained from control (MSCct) and malnourished (MSCmaln) animals were characterized. In addition, the proliferation rate and cell cycle protein expression were determined, but no differences in these parameters were observed. In order to evaluate whether PM affects the immunomodulatory properties of MSCs, the expression of NFκB and STAT-3, and the production of IL-1α, IL-1β, IL-6, IL-10, TGF-β and TNF-α by MSCs were assessed. MSCmaln expressed lower levels of NF-κB and the production of IL-1β, IL-6 and TGF-β was significantly influenced by PM. Furthermore, MSCct and MSCmaln culture supernatants affected lymphocyte and macrophage proliferation. However, MSCmaln did not reduce the production of IFN-γ nor stimulate the production of IL-10 in lymphocytes in the same manner as observed in MSCct. Overall, this study implied that PM modifies immunosuppressive properties of MSCs. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  4. Mining the Human Gut Microbiota for Immunomodulatory Organisms.

    Science.gov (United States)

    Geva-Zatorsky, Naama; Sefik, Esen; Kua, Lindsay; Pasman, Lesley; Tan, Tze Guan; Ortiz-Lopez, Adriana; Yanortsang, Tsering Bakto; Yang, Liang; Jupp, Ray; Mathis, Diane; Benoist, Christophe; Kasper, Dennis L

    2017-02-23

    Within the human gut reside diverse microbes coexisting with the host in a mutually advantageous relationship. Evidence has revealed the pivotal role of the gut microbiota in shaping the immune system. To date, only a few of these microbes have been shown to modulate specific immune parameters. Herein, we broadly identify the immunomodulatory effects of phylogenetically diverse human gut microbes. We monocolonized mice with each of 53 individual bacterial species and systematically analyzed host immunologic adaptation to colonization. Most microbes exerted several specialized, complementary, and redundant transcriptional and immunomodulatory effects. Surprisingly, these were independent of microbial phylogeny. Microbial diversity in the gut ensures robustness of the microbiota's ability to generate a consistent immunomodulatory impact, serving as a highly important epigenetic system. This study provides a foundation for investigation of gut microbiota-host mutualism, highlighting key players that could identify important therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Immunomodulatory effects of honey cannot be distinguished from endotoxin

    DEFF Research Database (Denmark)

    Timm, Michael; Bartelt, Stine; Hansen, Erik Wind

    2008-01-01

    in vitro effects of honey. Our results show that natural honeys induce interleukin-6 release from Mono Mac 6 cells as well as release of reactive oxygen species from all-trans retinoic acid (ATRA) differentiated HL-60 cells. The natural honeys contained substantial amounts of endotoxin, and the responses...... observed in the cell based assays were similar to the responses induced by endotoxin alone. In addition, we determined that the immunomodulatory component present in the natural honeys was retained in the ultra filtrated fraction with a molecular weight greater than 20 kDa. The component was resistant...... to boiling and its immunomodulatory activity could be abrogated by the addition of polymyxin B. We speculate that the observed in vitro immunomodulatory effects of honey might solely be explained by the endotoxin content in the natural honeys....

  6. Histones induce rapid and profound thrombocytopenia in mice

    Science.gov (United States)

    Bhandari, Ashish A.

    2011-01-01

    Histones are released from dying cells and contribute to antimicrobial defense during infection. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. We studied the interactions of histones with platelets. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Hereby fibrinogen cross-linked histone-bearing platelets and triggered microaggregation. Fibrinogen interactions with αIIbβ3 integrins were not required for this process but were necessary for the formation of large platelet aggregates. Infused histones associated with platelets in vivo and caused a profound thrombocytopenia within minutes after administration. Mice lacking platelets or αIIbβ3 integrins were protected from histone-induced death but not from histone-induced tissue damage. Heparin, at high concentrations, prevented histone interactions with platelets and protected mice from histone-induced thrombocytopenia, tissue damage, and death. Heparin and histones are evolutionary maintained. Histones may combine microbicidal with prothrombotic properties to fight invading microbes and maintain hemostasis after injury. Heparin may provide an innate counter mechanism to neutralize histones and diminish collateral tissue damage. PMID:21700775

  7. Immunomodulatory, antiglycation and anti-ulcerative properties of ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research August 2017; 16 (8): 1751-1755. ISSN: 1596-5996 ..... organ transplant rejection, cancer, rheumatoid arthritis, and systemic lupus erythematosus are currently treated with ... treatment of cancer.

  8. (Anti)mutagenic and immunomodulatory properties of quercetin glycosides

    Czech Academy of Sciences Publication Activity Database

    Valentová, Kateřina; Šíma, Petr; Rybková, Z.; Křižan, Jiří; Malachová, K.; Křen, Vladimír

    2016-01-01

    Roč. 96, č. 5 (2016), s. 1492-1499 ISSN 0022-5142 R&D Projects: GA ČR(CZ) GAP301/11/0767; GA MŠk(CZ) LD14096 Institutional support: RVO:61388971 Keywords : quercetin glycosides * (anti)mutagenicity * mice Subject RIV: EE - Microbiology, Virology Impact factor: 2.463, year: 2016

  9. Immunomodulatory, antiglycation and anti-ulcerative properties of ...

    African Journals Online (AJOL)

    maximal inhibitory concentration (IC50) of 39.48 ± 8.06 % using ibuprofen as standard and antiglycation effect (IC50 = 382.21 ± 3.43) using rutin as standard. The methanol extract of the aerial parts of the plant showed urease inhibition activity ...

  10. Immunomodulatory activity of methanol extract of Adansonia digitata L

    African Journals Online (AJOL)

    Purpose: To evaluate the immune-modulatory activities of various plant parts Adansonia digitata L. using delayed-type hypersensitivity rat model. Methods: Defatted leaf, root bark and fruit pulp of A. digitata were extracted with methanol. Immunomodulatory activity of the methanol extracts (250 and 500 mg/kg) were ...

  11. The Immunomodulatory Potential of Selected Bioactive Plant-Based Compounds in Breast Cancer: A Review.

    Science.gov (United States)

    Baraya, Yushau Shuaibu; Wong, Kah Keng; Yaacob, Nik Soriani

    2017-01-01

    Breast cancer has continued to cause high cancer death rates among women worldwide. The use of plants' natural products in breast cancer treatment has received more attention in recent years due to their potentially wider safety margin and the potential to complement conventional chemotherapeutic drugs. Plantbased products have demonstrated anticancer potential through different biological pathways including modulation of the immune system. Immunomodulatory properties of medicinal plants have been shown to mitigate breast cancer cell growth. Different immune cell types participate in this process especially cytotoxic T cells and natural killer cells, and cytokines including chemokines and tumor necrosis factor-α. Medicinal plants such as Glycyrrhiza glabra, Uncaria tomentosa, Camellia sinensis, Panax ginseng, Prunus armenaica (apricot), Allium sativum, Arctium lappa and Curcuma longa were reported to hold strong potential in breast cancer treatment in various parts of the world. Interestingly, research findings have shown that these plants possess bioactive immunomodulators as their main constituents producing the anticancer effects. These immunomodulatory compounds include ajoene, arctigenin, β-carotene, curcumin, epigallocatechin-3-gallate, ginsan, glabridin and quinic acid. In this review, we discussed the ability of these eight immunomodulators in regulating the immune system potentially applicable in breast cancer treatment via anti-inflammatory (curcumin, arctigenin, glabridin and ajoene) and lymphocytes activation (β-carotene, epigallocatechin-3-gallate, quinic acid and ginsan) properties, as well as future research direction in their use for breast cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Proximal processes of children with profound multiple disabilities

    OpenAIRE

    Wilder, Jenny

    2008-01-01

    In this thesis four empirical studies dealt with children with profound multiple disabilities and their parents with regard to: (a) how parents perceived interaction with their children (b) how observed child/parent interaction was linked to behavior style of the children as perceived by the parents (c) how parents of children with profound multiple disabilities perceived child/parent interaction and behavior style of their children in comparison to parents to children without disabilities ma...

  13. Evaluation of the immunomodulatory and DNA protective activities of the shoots of Cynodon dactylon.

    Science.gov (United States)

    Mangathayaru, K; Umadevi, M; Reddy, C Umamaheswara

    2009-05-04

    Fresh juice of Cyanodon dactylon known as 'durva' grass is employed in India as a rejuvenator and for wound healing. To validate the traditional use of the herb through evaluation of DNA protective activity in vitro and immunomodulatory activity in vivo. Fresh juice of the grass was prepared as indicated for use in traditional medicine and standardized for solid content. Its total phenol content was estimated by Folin-Ciocalteau method. Freshly prepared juice was investigated for its effect on doxorubicin-induced DNA damage in vitro. Its immunomodulatory activity was tested on balb/c mice by the humoral antibody response which was determined by haemagglutination antibody titer and spleen cell assay. Fresh juice of Cyanodon dactylon of 1.46% (w/w) solid content had a phenolic content of 47+/-0.33 mg/kg GAE. At doses equivalent to 50, 100 and 200mg total solids/kg body weight the juice protected human DNA against doxorubicin-induced DNA damage as demonstrated in DNA spectral studies, where the ratio of absorbance of DNA at 260 and 280 nm in samples pretreated with the juice was 1.66, 1.53 and 1.63 respectively, while it was 1.37 for DNA treated with doxorubicin only. This indicates nucleic acid purity in the Cynodon dactylon treated samples. Oral administration of the juice at 250 and 500 mg/kg in balb/c mice increased humoral antibody response upon antigen challenge, as evidenced by a dose-dependent, statistically significant increase in antibody titer in the haemagglutination antibody assay and plaque forming cell assay. The present report demonstrated the DNA protective activity and immunomodulatory property of the fresh juice of Cynodon dactylon validating the traditional use of the herb as a 'rasayana' in ayurvedic system of medicine.

  14. Immunomodulatory activity and chemical characterisation of sangre de drago (dragon's blood) from Croton lechleri.

    Science.gov (United States)

    Risco, Ester; Ghia, Felipe; Vila, Roser; Iglesias, José; Alvarez, Elida; Cañigueral, Salvador

    2003-09-01

    The immunomodulatory activity of the latex from Croton lechleri (sangre de drago) was determined by in vitro assays. Classical (CP) and alternative (AP) complement pathways activities were determined in human serum. Intracellular generation of reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) and monocytes, and phagocytosis of opsonised fluorescent microspheres were measured by flow cytometry. Free radical scavenging activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Activity on proliferation of murine lymphocytes was also investigated. In addition, anti-inflammatory activity was assayed in vivo by carrageenan-induced rat paw oedema test. Some of the activities were compared with those of the isolated alkaloid taspine. Sangre de drago from Croton lechleri showed immunomodulatory activity. It exhibited a potent inhibitory activity on CP and AP of complement system and inhibited the proliferation of activated T-cells. The latex showed free radical scavenging capacity. Depending on the concentration, it showed antioxidant or prooxidant properties, and stimulated or inhibited the phagocytosis. Moreover, the latex has strong anti-inflammatory activity when administered i. p. Taspine cannot be considered the main responsible for these activities, and other constituents, probably proanthocyanidins, should be also involved.

  15. Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis: a brief review

    Directory of Open Access Journals (Sweden)

    Marcio A. R. Araujo

    2011-09-01

    Full Text Available Many biological properties have been attributed to various types of propolis, including anti-inflammatory, antimicrobial, antioxidant, antitumor, wound healing, and immunomodulatory activities. This article reviewed studies published that investigated the anti-inflammatory activity of propolis of different origins and/or its isolated components, focusing on the mechanisms of action underlying this activity and also addressing some aspects of immunomodulatory effects. The search was performed of the following databases: PubMed, Science Direct, HighWire Press, Scielo, Google Academics, Research Gate and ISI Web of Knowledgement. The anti-inflammatory activity was associated with propolis or compounds such as polyphenols (flavonoids, phenolic acids and their esters, terpenoids, steroids and amino acids. CAPE is the most studied compounds. The main mechanisms underlying the anti-inflammatory activity of propolis included the inhibition of cyclooxygenase and consequent inhibition of prostaglandin biosynthesis, free radical scavenging, inhibition of nitric oxide synthesis, reduction in the concentration of inflammatory cytokines and immunosuppressive activity. Propolis was found to exert an anti-inflammatory activity in vivo and in vitro models of acute and chronic inflammation and others studies, indicating its promising potential as anti-inflammatory agent of natural origin and as a source of chemical compounds for the development of new drugs.

  16. Nanotechnological Inventions and Nanomaterials Produce A Profound Effect

    Directory of Open Access Journals (Sweden)

    VLASOV Vladimir Alexeevich

    2015-02-01

    Full Text Available The inventions in the area of nanotechnologies and nanomaterials produce a profound effect in construction, housing and communal services and adjacent economic fields as they allow us: to increase mechanical strength, coefficient of elasticity, alkali resistance and temperature of products vitrification; to obtain nanostructured coatings with the property of shape memory on the steel; to raise the dynamics of coal burning and its full burnout in the boilers of thermoelectric power station; to produce metal nanopowders with increased stored energy 10–15% etc. For example, the invention «Epoxy composition for high strength, alkali resistant structures» refers to epoxy composition used as a binder for production of high strength, thermal- and alkali-resistant glass-fiber material which can be applied in the manufacture process of construction reinforcement to strengthen concrete structures. The invention «The method to produce nanostructured reaction foil» can be used to join different materials including metal alloys, ceramics, amorphous materials and elements of microelectronic devices that are sensible to the heating. This process provides decreased labour-output ratio and energy consumption as well as the condition to manufacture foil with specified stored energy and high mechanical properties. The invention «The method of intensification of burning lowreactionary coal in the boilers of thermoelectric power station» refers to the thermal energy and can be implemented at the thermal plants. The increased dynamics of inflaming and burning leads to full burnout of powdered-coal low-reactionary fuel and decreased mechanical underfiring. The specialists may be also interested in the following inventions: fine dispersed organic suspension of carbon metal-containing nanostructures and the method to produce it; the dispersion of carbon nanotubes; the composition for reinforcement of building structures; the reinforced plate element made of

  17. Human dignity and the profoundly disabled: a theological perspective.

    Science.gov (United States)

    Matthews, Pia

    2011-01-01

    One challenge to the concept of human dignity is that it is a rootless notion invoked simply to mask inequalities that inevitably exist between human beings. This privileging of humans is speciesist and its weak point is the profoundly disabled human being. This article argues that far from being a weak point, the profoundly disabled person is a source of strength and witness to the intrinsic dignity that all human beings have by virtue of being human. The disabled represent the reality of human existence that is both strong and fragile. Although human dignity can be understood philosophically its depth is rooted in Christian theological insights. The profoundly disabled occupy a privileged position and share in a theology of mission since they testify to the interdependence of every human being and human dependence on God to a myopic world that only values strength, autonomy and independence.

  18. Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection

    Directory of Open Access Journals (Sweden)

    Jong Seok Lee

    2014-01-01

    Full Text Available Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8 probably in part through interference with the formation of reactive oxygen species by influenza A virus infection. Long-term oral administration of mice with RGE showed multiple immunomodulatory effects such as stimulating antiviral cytokine IFN-γ production after influenza A virus infection. In addition, RGE administration in mice inhibited the infiltration of inflammatory cells into the bronchial lumens. Therefore, RGE might have the potential beneficial effects on preventing influenza A virus infections via its multiple immunomodulatory functions.

  19. Immunomodulatory, Cytotoxicity, and Antioxidant Activities of Roots of Ziziphus mauritiana

    OpenAIRE

    Afzal, Samina; Batool, Murium; Ch, Bashir Ahmad; Ahmad, Ashfaq; Uzair, Muhammad; Afzal, Khurram

    2017-01-01

    Aims: The study is conducted to evaluate the immunomodulatory, cytotoxicity, and antioxidant potential of Ziziphus mauritiana (Rhamnaceae). Phytochemical analysis of Z. mauritiana revealed the presence of alkaloids, anthraquinone glycoside, cardiac glycoside, saponin, tannin, and flavonoids. Methodology: The cytotoxicity of the plant Z. mauritiana was evaluated by brine shrimp lethality test. Antioxidant parameters such as superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and ma...

  20. Fungal immunomodulatory proteins in the context of biomedicine.

    Science.gov (United States)

    Uribe-Echeverry, Paula Tatiana; Lopez-Gartner, German Ariel

    2017-06-01

    Fungi represent a large group of biodiverse microorganisms with potential applications ranging from industrial fields to the treatment for human diseases. A large number of pharmacologically active compounds including terpenoids, polysaccharides and proteins have been derived from these microorganisms. Fungal Immunomodulatory Proteins (FIPs) are a group of active compounds that are being considered for the treatment of asthma, allergy, autoimmune diseases and cancer. Here, we discuss the discovery, heterologous production bioactive mechanisms of action and their potential use in biomedicine.

  1. Development of QSAR model for immunomodulatory activity of natural coumarinolignoids

    Directory of Open Access Journals (Sweden)

    Dharmendra K Yadav

    2010-07-01

    Full Text Available Dharmendra K Yadav, Abha Meena, Ankit Srivastava, D Chanda, Feroz Khan, SK ChattopadhyayMetabolic and Structural Biology Department, Central Institute of Medicinal and Aromatic Plants, Council of Scientific and Industrial Research, PO-CIMAP, IndiaAbstract: Immunomodulation is the process of alteration in immune response due to foreign intrusion of molecules inside the body. Along with the available drugs, a large number of herbal drugs are promoted in traditional Indian treatments, for their immunomodulating activity. Natural coumarinolignoids isolated from the seeds of Cleome viscose have been recognized as having hepatoprotective action and have recently been tested preclinically for their immunomodulatory activity affecting both cell-mediated and humoral immune response. To explore the immunomodulatory compound from derivatives of coumarinolignoids, a quantitative structure activity relationship (QSAR and molecular docking studies were performed. Theoretical results are in accord with the in vivo experimental data studied on Swiss albino mice. Immunostimulatory activity was predicted through QSAR model, developed by forward feed multiple linear regression method with leave-one-out approach. Relationship correlating measure of QSAR model was 99% (R2 = 0.99 and predictive accuracy was 96% (RCV2 = 0.96. QSAR studies indicate that dipole moment, steric energy, amide group count, lambda max (UV-visible, and molar refractivity correlates well with biological activity, while decrease in dipole moment, steric energy, and molar refractivity has negative correlation. Docking studies also showed strong binding affinity to immunomodulatory receptors.Keywords: coumarinolignoids, immunomodulation, docking, QSAR, regression model

  2. Music Training for Severely and Profoundly Retarded Individuals.

    Science.gov (United States)

    Kesler, Buford; Richmond, Bert O.

    Investigated were the effects of sex, ability and training method on the musical instrument playing ability of 16 institutionalized severely and profoundly retarded persons ages 7 to 20 years. Ss were randomly assigned to one of four treatment groups, and the time required to reach criterion playing a familiar tune was recorded. Data indicated…

  3. Acceleration of Object Permanence with Severely and Profoundly Retarded Children.

    Science.gov (United States)

    Kahn, James V.

    Examined was the effectiveness of training four severely and profoundly retarded children (3-6 years old) to improve their level of functioning on a measure of object permanence and to demonstrate generalization to other areas of sensorimotor intelligence. Ss were given a pretest and posttest on the I. Uzgiris and J. Hunt instrument which consists…

  4. Factors which Motivate Job Acceptance and Profoundly Mentally Retarded Children.

    Science.gov (United States)

    Marozas, Donald S.; May, Deborah C.

    1980-01-01

    The study involving 360 Pennsylvania teachers was designed to identify factors which motivate job acceptance among teachers of severely and profoundly mentally retarded children. The responses of 235 teachers indicated that challenge and practicum experiences were the two most prevalent motivational factors underlying job acceptance. (Author)

  5. Pre-Language Activities for the Profoundly Mentally Retarded.

    Science.gov (United States)

    Poole, Marilyn R.; And Others

    Provided are sample lesson plans for a program to develop pre-language skills in profoundly retarded children and adults. Characteristic of the suggested activities is the stimulation of all sensory channels through structured infant-like play activities in five general areas: oral stimulation, sensory arousal, motor stimulation, vocal play, and…

  6. A Grounded Theory of Effective Reading by Profoundly Deaf Adults

    Science.gov (United States)

    Silvestri, Julia; Wang, Ye

    2018-01-01

    The purpose of the study was to uncover and describe psycholinguistic and sociocognitive factors facilitating effective reading by signing adults who are profoundly deaf and do not use hearing technology. The sample comprised four groups, each consisting of 15 adults, for a total of 60 participants. The four groups were "deaf…

  7. Deming's System of Profound Knowledge: An Overview for International Educators.

    Science.gov (United States)

    Evans, Thomas J.

    W. Edwards Deming called for the transformation to a new style of organizational management based on greater cooperation between managers and employees. This transformation could be achieved by introducing "profound knowledge" into the system. This paper is a presentation outline that was used to introduce the basics of Deming's theory…

  8. Immunomodulatory Polysaccharide from Chlorophytum borivilianum Roots

    Directory of Open Access Journals (Sweden)

    Mayank Thakur

    2011-01-01

    Full Text Available Chlorophytum borivilianum Santapau & Fernandes (Liliaceae is an ayurvedic Rasayana herb with immunostimulating properties. The polysaccharide fraction (CBP derived from hot water extraction of C. borivilianum (CB, comprising of ~31% inulin-type fructans and ~25% acetylated mannans (of hot water-soluble extract, was evaluated for its effect on natural killer (NK cell activity (in vitro. Human peripheral blood mononuclear cells (PBMCs, isolated from whole blood on a Ficoll-Hypaque density gradient, were tested in the presence or absence of varying concentrations of each C. borivilianum fraction for modulation of NK cell cytotoxic activity toward K562 cells. Preliminary cytotoxicity evaluation against P388 cells was performed to establish non-cytotoxic concentrations of the different fractions. Testing showed the observed significant stimulation of NK cell activity to be due to the CBP of C. borivilianum. Furthermore, in vivo evaluation carried out on Wistar strain albino rats for humoral response to sheep red blood cells (SRBCs and immunoglobulin-level determination using enzyme-linked immunosorbent assay (ELISA, exhibited an effectiveness of C. borivilianum aqueous extract in improving immune function. Present results provide useful information for understanding the role of CBP in modulating immune function.

  9. Human multipotent adult progenitor cells are nonimmunogenic and exert potent immunomodulatory effects on alloreactive T-cell responses.

    Science.gov (United States)

    Jacobs, Sandra A; Pinxteren, Jef; Roobrouck, Valerie D; Luyckx, Ariane; van't Hof, Wouter; Deans, Robert; Verfaillie, Catherine M; Waer, Mark; Billiau, An D; Van Gool, Stefaan W

    2013-01-01

    Multipotent adult progenitor cells (MAPCs) are bone marrow-derived nonhematopoietic stem cells with a broad differentiation potential and extensive expansion capacity. A comparative study between human mesenchymal stem cells (hMSCs) and human MAPCs (hMAPCs) has shown that hMAPCs have clearly distinct phenotypical and functional characteristics from hMSCs. In particular, hMAPCs express lower levels of MHC class I than hMSCs and cannot only differentiate into typical mesenchymal cell types but can also differentiate in vitro and in vivo into functional endothelial cells. The use of hMSCs as cellular immunomodulatory stem cell products gained much interest since their immunomodulatory capacities in vitro became evident over the last decade. Currently, the clinical grade stem cell product of hMAPCs is already used in clinical trials to prevent graft-versus-host disease (GVHD), as well as for the treatment of acute myocardial infarct, ischemic stroke, and Crohn's disease. Therefore, we studied the immune phenotype, immunogenicity, and immunosuppressive effect of hMAPCs in vitro. We demonstrated that hMAPCs are nonimmunogenic for T-cell proliferation and cytokine production. In addition, hMAPCs exert strong immunosuppressive effects on T-cell alloreactivity and on T-cell proliferation induced by mitogens and recall antigens. This immunomodulatory effect was not MHC restricted, which makes off-the-shelf use promising. The immunosuppressive effect of hMAPCs is partially mediated via soluble factors and dependent on indoleamine 2,3-dioxygenase (IDO) activity. At last, we isolated hMAPCs, the clinical grade stem cell product of hMAPCs, named MultiStem, and hMSCs from one single donor and observed that both the immunogenicity and the immunosuppressive capacities of all three stem cell products are comparable in vitro. In conclusion, hMAPCs have potent immunomodulatory properties in vitro and can serve as a valuable cell source for the clinical use of immunomodulatory cellular

  10. Do colors exist? and other profound physics questions

    CERN Document Server

    Cottrell, Seth Stannard

    2018-01-01

    Why do polished stones look wet? How does the Twin Paradox work? Why are orbits ellipses? How can we be sure that pi never repeats? How does a quantum computer break encryption? Discover the answers to these, and other profound physics questions! This fascinating book presents a collection of articles based on conversations and correspondences between the author and complete strangers about physics and math. The author, a researcher in mathematical physics, responds to dozens of questions posed by inquiring minds from all over the world, ranging from the everyday to the profound. Rather than unnecessarily complex explanations mired in mysterious terminology and symbols, the reader is presented with the reasoning, experiments, and mathematics in a casual, conversational, and often comical style. Neither over-simplified nor over-technical, the lucid and entertaining writing will guide the reader from the each innocent question to a better understanding of the weird and beautiful universe around us. Advance prai...

  11. Observations on Working Psychoanalytically with a Profoundly Amnesic Patient

    Directory of Open Access Journals (Sweden)

    Paul A. Moore

    2017-08-01

    Full Text Available Individuals with profound amnesia are markedly impaired in explicitly recalling new episodic events, but appear to preserve the capacity to use information from other sources. Amongst these preserved capacities is the ability to form new memories of an emotional nature – a skill at the heart of developing and sustaining interpersonal relationships. The psychoanalytic study of individuals with profound amnesia might contribute to the understanding the importance of each memory system, including effects on key analytic processes such as transference and countertransference. However, psychoanalytic work in the presence of profound amnesia might also require important technical modifications. In the first report of its kind, we describe observations from a long term psychoanalytic process (72 sessions with an individual (JL who has profound amnesia after an anoxic episode. The nature of therapy was shaped by JL’s impairment in connecting elements that belong to distant (and even relatively close moments in the therapeutic process. However, we were also able to document areas of preservation, in what appears to be a functioning therapeutic alliance. As regards transference, the relationship between JL and his analyst can be viewed as the evolution of a narcissistic transference, and case material is provided that maps this into three phases: (i rejecting; (ii starting to take in; and (iii full use of the analytic space – where each phase exhibits differing degrees of permeability between JL and the analyst. This investigation appears to have important theoretical implications for psychoanalytic practice, and for psychotherapy in general – and not only with regard to brain injured populations. We especially note that it raises questions concerning the mechanism of therapeutic action in psychoanalysis and psychotherapy, and the apparent unimportance of episodic memory for many elements of therapeutic change.

  12. Foveal Processing Under Concurrent Peripheral Load in Profoundly Deaf Adults

    Science.gov (United States)

    2016-01-01

    Development of the visual system typically proceeds in concert with the development of audition. One result is that the visual system of profoundly deaf individuals differs from that of those with typical auditory systems. While past research has suggested deaf people have enhanced attention in the visual periphery, it is still unclear whether or not this enhancement entails deficits in central vision. Profoundly deaf and typically hearing adults were administered a variant of the useful field of view task that independently assessed performance on concurrent central and peripheral tasks. Identification of a foveated target was impaired by a concurrent selective peripheral attention task, more so in profoundly deaf adults than in the typically hearing. Previous findings of enhanced performance on the peripheral task were not replicated. These data are discussed in terms of flexible allocation of spatial attention targeted towards perceived task demands, and support a modified “division of labor” hypothesis whereby attentional resources co-opted to process peripheral space result in reduced resources in the central visual field. PMID:26657078

  13. NEW MEAT PRODUCTS WITH IMMUNOMODULATORY EFFECT CREATION METHOD

    Directory of Open Access Journals (Sweden)

    I. V. Kaltovich

    2016-01-01

    Full Text Available New meat products with immunomodulatory effect creation method reflecting differential characteristics of technological stages of manufacture of those types of meat products, including issues on the selection of primary and secondary raw materials, guidelines for development of formulations and production technologies, legislative requirements towards its labeling, etc, has been developed for the first time. A list of prospective meat raw materials for the manufacture of products with immunomodulatory effect was established: beef, pork, rabbit meat, broiler chicken meat, turkey, veal, ostrich meat, which have high content of protein (14,3– 21,7%, low content of fat (1,2–16,1%, excluding pork (33,3%, high levels of minimum amino-acid score (90,0–104,0%, protein quality indicator(0,91–1,64, essential amino acid index (1,16-1,25, coefficient of utility of amino acid content (0,72–0,86 and close to optimum fatty acid content, and also contain a great number of vitamins and minerals which play a significant role for immunity improvement. It was determined that the following functional ingredients are recommended to use: amino acids (valine, leucine, isoleucine, methionine, threonine, arginine, tryptophan, lysine, histidin, phenylalanyl, vitamins and provitamins (C,E, beta-carotene, B vitamins(Bc, B12, PP, etc., P(bioflavonoid complex, H, K, minerals (calcium, magnesium, iron, cuprum, zinc, manganese, selenium, polyunsaturated fatty acids omega-3 and omega-6, pseudo-vitamins (L-carnitin, coenzyme Q10, polysaccharides and peptides naturally occurring(squalen, B-Carotene, ginger, shiitake mushrooms, probiotics and prebiotics, glutathione, indole and lycopienes, bioflavonoids, L-arginine, N-acetylcysteine, gel from seaweed «Lamifaren». The use of the developed meat products with immunomodulatory effect creation method by process engineers of meat processing factories will allow them to form a single scientifically grounded approach during the

  14. Central neurotoxicity of immunomodulatory drugs in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Urmeel H. Patel

    2015-03-01

    Full Text Available Immunomodulatory drugs (IMiDs currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient, lenalidomide (4 patients, and pomalidomide (1 patient was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

  15. Central neurotoxicity of immunomodulatory drugs in multiple myeloma.

    Science.gov (United States)

    Patel, Urmeel H; Mir, Muhammad A; Sivik, Jeffrey K; Raheja, Divisha; Pandey, Manoj K; Talamo, Giampaolo

    2015-02-24

    Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

  16. A model of immunomodulatory for dengue infection mm

    Science.gov (United States)

    Zulfa, Annisa; Handayani, Dewi; Nuraini, Nuning

    2018-03-01

    An immunomodulatory model for dengue infection is constructed in this paper. This study focuses on T-cell compartments and B cells that are immune cells involved in the dengue infection process. Dengue virus-infected monocyte cells release interferons to signal T-cells to activate B-cells and produce antibodies. Immunomodulator acts as a treatment control and aims to increase the numbers of antibodies so it is expected to reduce the number of infected monocyte cells by dengue virus. Numerical simulation shows that the greater the rate of f (t) the immune cells will be stimulated to suppress the number of infected cells.

  17. In vitro pyrogen test for toxic or immunomodulatory drugs

    OpenAIRE

    Daneshian, Mardas; Guenther, Armin; Wendel, Albrecht; Hartung, Thomas; Aulock, Sonja von

    2006-01-01

    Pyrogenic contaminations of some classes of injectable drugs, e.g. toxic or immunomodulatory as well as false-positive drugs, represent a major risk which cannot yet be excluded due to the limitations of current tests. Here we describe a modification of the In vitro Pyrogen Test termed AWIPT (Adsorb, Wash, In vitro Pyrogen Test), which addresses this problem by introducing a pre-incubation step in which pyrogenic contaminations in the test sample are adsorbed to albumin-coated beads. After ri...

  18. Driving to learn in a powered wheelchair: the process of learning joystick use in people with profound cognitive disabilities.

    Science.gov (United States)

    Nilsson, Lisbeth; Eklund, Mona; Nyberg, Per; Thulesius, Hans

    2011-01-01

    The Driving to Learn project explored ways to help people with profound cognitive disabilities practice operating a joystick-operated powered wheelchair. The project used a grounded theory approach with constant comparative analysis and was carried out over 12 yr. The participants were 45 children and adults with profound cognitive disabilities. Reference groups included 17 typically developing infants and 64 participants with lesser degrees of cognitive disability. The data sources included video recordings, field notes, open interviews, and a rich mixture of literature. The findings that emerged yielded strategies for facilitating achievements, an 8-phase learning process, an assessment tool, and a grounded theory of deplateauing explaining the properties necessary for participants to exceed expected limitations and plateaus. Eight participants with profound cognitive disabilities reached goal-directed driving or higher. Participants were empowered by attaining increased control over tool use, improving their autonomy and quality of life.

  19. Immunomodulatory Effect of Rhaphidophora korthalsii on Natural Killer Cell Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Swee Keong Yeap

    2012-01-01

    Full Text Available The in vivo immunomodulatory effect of ethanolic extracts from leaves of Rhaphidophora korthalsii was determined via immune cell proliferation, T/NK cell phenotyping, and splenocyte cytotoxicity of BALB/c mice after 5 consecutive days of i.p. administration at various concentrations. Splenocyte proliferation index, cytotoxicity, peripheral blood T/NK cell population, and plasma cytokine (IL-2 and IFN-γ in mice were assessed on day 5 and day 15. High concentration of extract (350 μg/mice/day for 5 consecutive days was able to stimulate immune cell proliferation, peripheral blood NK cell population, IL-2, and IFN- γ cytokines, as well as splenocyte cytotoxicity against Yac-1 cell line. Unlike rIL-2 which degraded rapidly, the stimulatory effect from the extract managed to last until day 15. These results suggested the potential of this extract as an alternative immunostimulator, and they encourage further study on guided fractionation and purification to identify the active ingredients that contribute to this in vitro and in vivo immunomodulatory activity.

  20. Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy

    Science.gov (United States)

    Nau, Gerard J.; Ross, Ted M.; Evans, Thomas G.; Chakraborty, Krishnendu; Empey, Kerry M.; Flynn, JoAnne L.

    2014-01-01

    Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The “Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy” session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials. PMID:25148426

  1. Challenges and future in vaccines, drug development, and immunomodulatory therapy.

    Science.gov (United States)

    Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L

    2014-08-01

    Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.

  2. Characterization and immunomodulatory activity of polysaccharides derived from Dendrobium tosaense.

    Science.gov (United States)

    Yang, Li-Chan; Lu, Ting-Jang; Hsieh, Chang-Chi; Lin, Wen-Chuan

    2014-10-13

    Dendrobium tosaense is a medicinal Dendrobium species widely used in traditional medicine. This study demonstrated some structural characterizations and immunomodulatory activity of the water-soluble polysaccharides derived from the stem of D. tosaense (DTP). DTP was fractioned using DEAE-650 M anion-exchange gel filtration chromatography, producing one neutral polysaccharide fraction (DTP-N), which was investigated for its structural characteristics, using HPAEC-PAD, HP-SEC, GC-MS, and NMR spectroscopy. DTP and DTP-N consisted of galactose, glucose, and mannose in ratios of 1:9.1:150.7 and 1:12.2:262.5, respectively. DTP-N comprised (1 → 4)Man as its main backbone, and its average molecular weight was 220 kDa. We also investigated the immunomodulatory effects of DTP administered orally to BALB/c mice for 3 weeks. DTP substantially boosted the population of splenic natural killer (NK) cells, NK cytotoxicity, macrophage phagocytosis, and cytokine induction in splenocytes. This is the first study to demonstrate the structural characteristics of an active polysaccharide derived from D. tosaense and its immunopharmacological effects in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Immunomodulatory Effects of Soybeans and Processed Soy Food Compounds.

    Science.gov (United States)

    Tezuka, Hiroyuki; Imai, Shinjiro

    2015-01-01

    Inflammation is an immune response against both internal and external antigens in organisms, particularly in mammals, and includes both uncontrolled chronic and low-grade inflammations. Uncontrolled chronic inflammation often leads to severe diseases such as vascular disease, arthritis, cancer, diabete, allergy, and autoimmunity. On the other hand, low-grade inflammation is recognized as a relationship between obesity and risk of metabolic syndrome. Elevated production of pro-inflammatory cytokines and mediators is commonly observed in patients with uncontrolled or low-grade inflammation-associated diseases. Plants have been generated phytochemicals to overcome inflammations and infections through evolution. Phytochemicals belong to alkaloids, polyphenols, flavonoids, coumarins, and terpenoids. The consumption of soybeans plays a role in immune modulation through their components such as isoflavones, saponins, and anthocyanins. Recently, it was reported that the application of phytochemicals into patients with inflammatory diseases improves their symptoms. Therefore, it is important to identify novel phytochemicals with immunomodulatory activities. This review introduces and discusses recent advances and patents regarding soybean or processed soy food compounds which exhibit immunomodulatory activity in immune diseases, particularly allergy, by mediating the suppression of inflammatory pathways.

  4. Development of immunotoxicity testing strategies for immunomodulatory drugs.

    Science.gov (United States)

    Kawabata, Thomas T; Evans, Ellen W

    2012-01-01

    The ICH S8 immunotoxicity testing guideline for human pharmaceuticals was published in 2006 and was intended to provide guidance for assessing the immunotoxicity potential of low-molecular-weight drugs that are not intended to alter the immune system. For drugs intended to modulate the immune system, immunotoxicity testing strategies are generally developed on a case-by-case approach since the targets, intended patient population, and mechanisms of action of the test compound will determine the type of testing needed. Some of the general principles of ICH S8, however, may be applied to immunotoxicity testing strategies for immunomodulatory drugs. A weight-of-evidence approach using factors discussed in ICH S8 in concert with an assessment of the potential value of additional immunotoxicity testing should be considered. For most situations, immunotoxicity studies with immunomodulatory compounds evaluate off-target effects on the immune system and exaggerated pharmacology. The potential use of data from these studies and considerations such as translatability to humans are discussed.

  5. Immunomodulatory effects of the fungicide Mancozeb in agricultural workers

    International Nuclear Information System (INIS)

    Corsini, Emanuela; Birindelli, Sarah; Fustinoni, Silvia; De Paschale, Gioia; Mammone, Teresa; Visentin, Sara; Galli, Corrado L.; Marinovich, Marina; Colosio, Claudio

    2005-01-01

    Available data suggest that ethylenebisdithiocarbamates (EBDCs) may have immunomodulatory effects. This study aimed to investigate the immunological profile of farmers exposed to Mancozeb, an EBDC fungicide, through the determination of several serum, cellular, and functional immune parameters. Twenty-six healthy subjects entered the study, 13 vineyards exposed to Mancozeb and 13 unexposed controls. Exposure was assessed through the determination of ethylentiourea (ETU) in urine. Complete and differential blood count, serum immunoglobulins, complement fractions, autoantibodies, lymphocyte subpopulations, proliferative response to mitogens, natural killer (NK) activity, and cytokine production were measured. Post-exposure samples showed ETU urine concentration significantly higher than pre-exposure and control groups. A significant increase in CD19+ cells, both percentage and absolute number, and a significant decrease in the percentage of CD25+ cells were found in post-exposure samples compared to controls. A statistically significant increase in the proliferative response to phorbol myristate acetate plus ionomycin (PMA + ionomycin) was observed in the post-exposure group compared to controls and baseline, while a significant reduction in LPS-induced TNF-α release in post-exposure samples was observed. Overall, our results suggest that low-level exposure to Mancozeb has slight immunomodulatory effects, and point out a method adequate to reveal immune-modifications in workers occupationally exposed to potential immunotoxic compounds, based on a whole blood assay

  6. Bipolar Affective Disorder in a Patient of Profound Deafness.

    Science.gov (United States)

    Zubair, Usama Bin; Mumtaz, Humza; Mansoor, Sawera

    2018-03-01

    Profound deafness is a lifelong impairment, leading to the physical disability as well as poor psychological adjustment. We herein present a mental health disorder rarely seen among the patients of profound deafness. A 16-year deaf and dumb girl, previously treated for depression, presented with unusual laughter, irritability, flight of ideas, decreased sleep, ideas of self importance, and decreased social functioning and educational performance. These problems were understood by the parents via sign language, who interpreted them to the interviewer. Her Young Mania Rating Scale (YMRS) score was 19 and Brief Psychiatric Rating Scale (BPRS) score was 52. She was diagnosed as a case of bipolar affective disorder (BPAD). Marked improvement in the symptoms and social and educational performance was noted after two weeks of the treatment with sodium valproate, resperidone and clonazepam. Treatment options were explained to the patient with risks and benefits, and she was involved in the decision-making. This case report highlights the importance of accurately diagnosing and managing a rare mental health disorder among the physically handicapped people, especially those who cannot communicate effectively and explain their unusual subjective experiences.

  7. Antileishmanial and Immunomodulatory Activity of Allium sativum (Garlic): A Review.

    Science.gov (United States)

    Foroutan-Rad, Masoud; Tappeh, Khosrow Hazrati; Khademvatan, Shahram

    2017-01-01

    Leishmaniasis is caused by an obligate intracellular protozoa belonging to Leishmania genus. The current drugs for treatment of leishmaniasis possess many disadvantages; therefore, researchers are continuously looking for the more effective and safer drugs. The aim of this study is to review the effectiveness, toxicities, and possible mechanisms of pharmaceutical actions of different garlic extracts and organosulfur compounds isolated from garlic against Leishmania spp. in a variety of in vitro, in vivo and clinical trials reports. All relevant databases were searched using the terms "Allium sativum," "Garlic," "Allicin," "Ajoene," "Leishmania," "in vitro," "in vivo," and "clinical trial," alone or in combination from 5 English databases (Web of Science, PubMed, Science Direct, Scopus, Google Scholar) and 3 Persian databases (Scientific Information Database, Iran Medex, and Magiran) from 1990 to 2014. In summary, garlic with immunomodulatory effects and apoptosis induction contributes to the treatment of leishmaniasis. © The Author(s) 2015.

  8. Immunomodulatory effect of vitamin K2: Implications for bone health.

    Science.gov (United States)

    Myneni, V D; Mezey, E

    2018-03-01

    In women with postmenopausal osteoporosis, vitamin K2 appears to decrease the incidence of hip, vertebral, and non-vertebral fractures. Women with postmenopausal osteoporosis have more circulating activated T cells compared with healthy postmenopausal and premenopausal women, but the effects of vitamin K2 on T cells have not been studied. In this study, we have looked at T-cell suppression by vitamin K2. Peripheral blood mononuclear cells (PBMCs) from three healthy donors were used. The PBMCs were stimulated with the mitogens phytohemagglutinin and concanavalin A, and T-cell proliferation was analyzed using flow cytometry based on carboxyfluorescein succinimidyl ester (CSFE) dye dilution. Vitamin K2 (60 and 100 μM) inhibited T-cell proliferation. Vitamin K1 at the same concentrations did not inhibit T-cell proliferation. Vitamin K2 has immunomodulatory activities. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  9. An evolutionary perspective on the immunomodulatory role of hydrogen sulphide.

    Science.gov (United States)

    Rivers-Auty, J

    2015-11-01

    Most preclinical studies on endogenous hydrogen sulphide signalling have given little consideration to the fact that the human body contains more bacterial cells than human cells, and that evolution provides the context for all biology. Whether hydrogen sulphide is pro or anti-inflammatory is heavily debated within the literature, yet researchers have not fully considered that invasive bacteria produce hydrogen sulphide, often at levels far above the endogenous levels of the host. Here I argue that if hydrogen sulphide is an endogenous signalling molecule with immunomodulatory functions, then it must have evolved in the presence of virulent bacteria which produce hydrogen sulphide. This context leads to two competing theories about the evolution of endogenous hydrogen sulphide signalling. The detectable emission theory proposes that bacteria produce hydrogen sulphide as part of normal metabolism and hosts which evolved to detect and respond to this hydrogen sulphide would gain a selective survival advantage. This predicts that the endogenous production of hydrogen sulphide is a mechanism which amplifies the bacterial hydrogen sulphide signal. The opposing protective agent theory predicts that bacterial hydrogen sulphide is an effective defence against the bactericidal mechanisms of the host's immune response. In this case, endogenous hydrogen sulphide production is either at inconsequential levels to alter the immune response, or is involved in the inflammation resolution process. Evidence suggests that the direct interactions of hydrogen sulphide with the bactericidal mechanisms of the innate immune system are most congruent with the protective agent theory. Therefore, I argue that if hydrogen sulphide is an immunomodulatory endogenous signalling molecule its effects are most likely anti-inflammatory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Use of Immunomodulatory Drugs at a Uveitis Clinic.

    Science.gov (United States)

    Millán-Longo, Claudia; Peiteado, Diana; Schlincker, Armelle; Hidalgo, Ventura; Pieren, Amara; Balsa, Alejandro; de Miguel, Eugenio

    2017-11-10

    The treatment of noninfectious uveitis includes steroids and immunomodulatory drugs, the use of which has increased in the last few years, and the options have been enriched with the development of new treatments. However, clear therapeutic guidelines and protocols have not been developed. The purpose is to analyze the response to the drugs used and the characteristics of the patients treated at a multidisciplinary uveitis clinic. Observational and retrospective study of the patients attended to from January 2012 to December 2015. Infectious, posttraumatic and postoperative uveitis, as well as masquerade syndrome, were excluded. Two hundred six patients were included. Overall, 58.80% had uveitis without association of systemic disease, mostly idiopathic uveitis, and 35.65% had uveitis with systemic involvement, mainly related to spondyloarthritis. Uveitis without systemic association and anterior uveitis achieved disease control with local treatment more frequently than others (p=.002 and p treatment. Among those treated with immunomodulators, 53.26% needed a second drug and 31.52% needed a third drug. Women required immunomodulators more often than men (P=.042). Methotrexate was the most widely used immunomodulator. Posterior uveitis responded less favorably to the second immunomodulator than anterior uveitis (p=.006). Almost half of the patients needed an immunomodulatory drug and some of them required successive drug changes. Intermediate uveitis was the most treatment-refractory uveitis. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  11. Immunomodulatory dietary polysaccharides: a systematic review of the literature

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    Nelson Erika D

    2010-11-01

    Full Text Available Abstract Background A large body of literature suggests that certain polysaccharides affect immune system function. Much of this literature, however, consists of in vitro studies or studies in which polysaccharides were injected. Their immunologic effects following oral administration is less clear. The purpose of this systematic review was to consolidate and evaluate the available data regarding the specific immunologic effects of dietary polysaccharides. Methods Studies were identified by conducting PubMed and Google Scholar electronic searches and through reviews of polysaccharide article bibliographies. Only articles published in English were included in this review. Two researchers reviewed data on study design, control, sample size, results, and nature of outcome measures. Subsequent searches were conducted to gather information about polysaccharide safety, structure and composition, and disposition. Results We found 62 publications reporting statistically significant effects of orally ingested glucans, pectins, heteroglycans, glucomannans, fucoidans, galactomannans, arabinogalactans and mixed polysaccharide products in rodents. Fifteen controlled human studies reported that oral glucans, arabinogalactans, heteroglycans, and fucoidans exerted significant effects. Although some studies investigated anti-inflammatory effects, most studies investigated the ability of oral polysaccharides to stimulate the immune system. These studies, as well as safety and toxicity studies, suggest that these polysaccharide products appear to be largely well-tolerated. Conclusions Taken as a whole, the oral polysaccharide literature is highly heterogenous and is not sufficient to support broad product structure/function generalizations. Numerous dietary polysaccharides, particularly glucans, appear to elicit diverse immunomodulatory effects in numerous animal tissues, including the blood, GI tract and spleen. Glucan extracts from the Trametes versicolor

  12. Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies

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    Morton, Laura Dill; Spindeldreher, Sebastian; Kiessling, Andrea; Allenspach, Roy; Hey, Adam; Muller, Patrick Y; Frings, Werner; Sims, Jennifer

    2010-01-01

    Most therapeutic monoclonal antibodies (mAbs) licensed for human use or in clinical development are indicated for treatment of patients with cancer and inflammatory/autoimmune disease and as such, are designed to directly interact with the immune system. A major hurdle for the development and early clinical investigation of many of these immunomodulatory mAbs is their inherent risk for adverse immune-mediated drug reactions in humans such as infusion reactions, cytokine storms, immunosuppression and autoimmunity. A thorough understanding of the immunopharmacology of a mAb in humans and animals is required to both anticipate the clinical risk of adverse immunotoxicological events and to select a safe starting dose for first-in-human (FIH) clinical studies. This review summarizes the most common adverse immunotoxicological events occurring in humans with immunomodulatory mAbs and outlines non-clinical strategies to define their immunopharmacology and assess their immunotoxic potential, as well as reduce the risk of immunotoxicity through rational mAb design. Tests to assess the relative risk of mAb candidates for cytokine release syndrome, innate immune system (dendritic cell) activation and immunogenicity in humans are also described. The importance of selecting a relevant and sensitive toxicity species for human safety assessment in which the immunopharmacology of the mAb is similar to that expected in humans is highlighted, as is the importance of understanding the limitations of the species selected for human safety assessment and supplementation of in vivo safety assessment with appropriate in vitro human assays. A tiered approach to assess effects on immune status, immune function and risk of infection and cancer, governed by the mechanism of action and structural features of the mAb, is described. Finally, the use of immunopharmacology and immunotoxicity data in determining a minimum anticipated biologic effect Level (MABEL) and in the selection of safe human

  13. Persistent Thalamic Sound Processing Despite Profound Cochlear Denervation

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    Anna R. Chambers

    2016-08-01

    Full Text Available Neurons at higher stages of sensory processing can partially compensate for a sudden drop in input from the periphery through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where > 95% of synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore the cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, cortical processing and perception recover despite the absence of an auditory brainstem response (ABR or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC, an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the auditory cortex (ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB of awake mice. Sound-driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory

  14. Profound hyper natremia due to central diabetes insipidus

    International Nuclear Information System (INIS)

    Vaqar, A.; Javaid, K.H.; Parveen, R.; Sadaf, R.

    2012-01-01

    Diabetes insipidus is a rare endocrine disorder in paediatric patients. Polyuria is a cardinal manifestation that is extremely difficult to recognize in diapered infants. Careful urine quantification is the key to diagnosis in appropriate clinical setting. We report a case of a 4 months old infant presenting with an acute life threatening event following an episode of vomiting and decreased oral intake. She had profound hyper natremia which persisted after stabilization. Polyuria unrecognized by the mother was revealed by 24-hour urine output measurement. A diagnosis of diabetes insipidus was made after appropriate laboratory investigations including serum and urine osmolality. The central nature of the disease was confirmed by neuroimaging which showed holoprosencephaly. (author)

  15. Thermal treatment of luteolin-7-O-β-glucoside improves its immunomodulatory and antioxidant potencies.

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    Maatouk, Mouna; Mustapha, Nadia; Mokdad-Bzeouich, Imen; Chaaban, Hind; Abed, Besma; Iaonnou, Irina; Ghedira, Kamel; Ghoul, Mohamed; Ghedira, Leila Chekir

    2017-11-01

    Phytochemicals extracted from flowers, roots and bark, leaves, and other plant sources have been used extensively throughout human history with varying levels of efficacy in prevention and treatment of disease. Recently, advanced methods for characterization and clinical use of these materials have allowed modern understanding of their properties to be used as immunomodulatory agents that act by enhancement of endogenous cytoprotective mechanisms, avoiding interference with normal physiologic signaling and highly effective medical treatment with minimal adverse side effects. Simple methods have been identified for improving their biological effects, such as thermal conditioning by heating or freezing-prominent example being heat treatment of lycopene and tetrahydrocannabinol. The present investigation shows improvement of the ability of heat to augment splenocyte proliferation, natural killer (NK) cell activities, and antioxidant capacity of the flavonoid luteolin-7-O-β-glucoside (L7G) in comparison with the native (non heat-treated) molecule, while further demonstrating that both the native and the heat-treated variants exhibit comparable antioxidant properties, as evidenced by their effects in macrophages by inhibition of nitric oxide production and lysosomal enzyme activity in experiments that strengthen lysosomal membrane integrity. Outcomes of these studies suggest that heat-treated L7G shows promise for use in immunotherapy, including anti-cancer regimens, as shown by its improvement of NK cell cytotoxicity.

  16. Genomic diversity and immunomodulatory activity of Lactobacillus plantarum isolated from dairy products.

    Science.gov (United States)

    Zago, M; Scaltriti, E; Bonvini, B; Fornasari, M E; Penna, G; Massimiliano, L; Carminati, D; Rescigno, M; Giraffa, G

    2017-08-24

    In this study, we aimed to investigate some functional characteristics and the immunomodulatory properties of three strains of Lactobacillus plantarum of dairy origin which, in a previous screening, showed to be candidate probiotics. Genome sequencing and comparative genomics, which confirmed the presence of genes involved in folate and riboflavin production and in the immune response of dendritic cells (DCs), prompted us to investigate the ability of the three strains to accumulate the two vitamins and their immunomodulation properties. The ability of the three strains to release antioxidant components in milk was also investigated. Small amounts of folate and riboflavin were produced by the three strains, while they showed a good antioxidant capacity in milk with FRAP method. The immune response experiments well correlated with the presence of candidate genes influencing in DCs cytokine response to L. plantarum. Specifically, the amounts of secreted cytokins by DCs after stimulation with cells of Lp790, Lp813 and Lp998 resulted pro-inflammatory whereas stimulation with culture supernatants (postbiotics) inhibited the release of interleukin (IL)-12p70 and increased the release of the anti-inflammatory IL-10 cytokine. This study adds further evidence on the importance of L. plantarum in human health. Understanding how probiotics (or postbiotics) work in preclinical models can allow a rational choice of the different strains for clinical and/or commercial use.

  17. Chemical composition and phagocyte immunomodulatory activity of Ferula iliensis essential oils.

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    Özek, Gulmira; Schepetkin, Igor A; Utegenova, Gulzhakhan A; Kirpotina, Liliya N; Andrei, Spencer R; Özek, Temel; Başer, Kemal Hüsnü Can; Abidkulova, Karime T; Kushnarenko, Svetlana V; Khlebnikov, Andrei I; Damron, Derek S; Quinn, Mark T

    2017-06-01

    Essential oil extracts from Ferula iliensis have been used traditionally in Kazakhstan for treatment of inflammation and other illnesses. Because little is known about the biologic activity of these essential oils that contributes to their therapeutic properties, we analyzed their chemical composition and evaluated their phagocyte immunomodulatory activity. The main components of the extracted essential oils were ( E )-propenyl sec -butyl disulfide (15.7-39.4%) and ( Z )-propenyl sec -butyl disulfide (23.4-45.0%). Ferula essential oils stimulated [Ca 2+ ] i mobilization in human neutrophils and activated ROS production in human neutrophils and murine bone marrow phagocytes. Activation of human neutrophil [Ca 2+ ] i flux by Ferula essential oils was dose-dependently inhibited by capsazepine, a TRPV1 channel antagonist, indicating that TRPV1 channels mediate this response. Furthermore, Ferula essential oils stimulated Ca 2+ influx in TRPV1 channel-transfected HEK293 cells and desensitized the capsaicin-induced response in these cells. Additional molecular modeling with known TRPV1 channel agonists suggested that the active component is likely to be ( Z )-propenyl sec -butyl disulfide. Our results provide a cellular and molecular basis to explain at least part of the beneficial therapeutic properties of FEOs. © Society for Leukocyte Biology.

  18. Otolithic organ function in patients with profound sensorineural hearing loss

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    Yujuan Zhou

    2016-06-01

    Full Text Available Profound sensorineural hearing loss (PSHL is not uncommonly encountered in otology. In clinics, there is a high incidence of otolithic damage in patients with PSHL, but relevant reports are few. Sharing a continuous membranous structure and similar receptor cell ultrastructures, the cochlea and vestibule may be susceptible to the same harmful factors. Disorders of the inner ear may result in a variety of manifestations, including vertigo, spatial disorientation, blurred vision, impaired articulation, and hearing impairment. Considering the diversity of clinical symptoms associated with PSHL with otolithic dysfunction, it may be frequently misdiagnosed, and objective means of testing the function of otolithic organs should be recommended for hearing-impaired patients. Vestibular-evoked myogenic potentials (VEMPs via air-conducted sound are of great importance for the diagnosis of otolithic function. Hearing devices such as cochlear implants are commonly accepted treatments for PSHL, and early identification and treatment of vestibular disorders may increase the success rate of cochlear implantation. Therefore, it is necessary to increase awareness of otolithic functional states in patients with PSHL.

  19. Cancer prevention knowledge of people with profound hearing loss.

    Science.gov (United States)

    Zazove, Philip; Meador, Helen E; Reed, Barbara D; Sen, Ananda; Gorenflo, Daniel W

    2009-03-01

    Deaf persons, a documented minority population, have low reading levels and difficulty communicating with physicians. The effect of these on their knowledge of cancer prevention recommendations is unknown. A cross-sectional study of 222 d/Deaf persons in Michigan, age 18 and older, chose one of four ways (voice, video of a certified American Sign Language interpreter, captions, or printed English) to complete a self-administered computer video questionnaire about demographics, hearing loss, language history, health-care utilization, and health-care information sources, as well as family and social variables. Twelve questions tested their knowledge of cancer prevention recommendations. The outcome measures were the percentage of correct answers to the questions and the association of multiple variables with these responses. Participants averaged 22.9% correct answers with no gender difference. Univariate analysis revealed that smoking history, types of medical problems, last physician visit, and women having previous cancer preventive tests did not affect scores. Improved scores occurred with computer use (p = 0.05), higher education (p internet (p = 0.02), and believing that smoking is bad (p bad (p = 0.05) were associated with improved scores. Persons with profound hearing loss have poor knowledge of recommended cancer prevention interventions. English use in multiple settings was strongly associated with increased knowledge.

  20. Discovery of the target for immunomodulatory drugs (IMiDs).

    Science.gov (United States)

    Ito, Takumi; Ando, Hideki; Handa, Hiroshi

    2016-05-01

    Half a century ago, the sedative thalidomide caused a serious drug disaster because of its teratogenicity and was withdrawn from the market. However, thalidomide, which has returned to the market, is now used for the treatment of leprosy and multiple myeloma (MM) under strict control. The mechanism of thalidomide action had been a long-standing question. We developed a new affinity bead technology and identified cereblon (CRBN) as a thalidomide-binding protein. We found that CRBN functions as a substrate receptor of an E3 cullin-Ring ligase complex 4 (CRL4) and is a primary target of thalidomide teratogenicity. Recently, new thalidomide derivatives, called immunomodulatory drugs (IMiDs), have been developed by Celgene. Among them, lenalidomide (Len) and pomalidomide (Pom) were shown to exert strong therapeutic effects against MM. It was found that Len and Pom both bind CRBN-CRL4 and recruit neomorphic substrates (Ikaros and Aiolos). More recently it was reported that casein kinase 1a (Ck1a) was identified as a substrate for CRBN-CRL4 in the presence of Len, but not Pom. Ck1a breakdown explains why Len is specifically effective for myelodysplastic syndrome with 5q deletion. It is now proposed that binding of IMiDs to CRBN appears to alter the substrate specificity of CRBN-CRL4. In this review, we introduce recent findings on IMiDs.

  1. Antileishmanial and Immunomodulatory Activity of Allium sativum (Garlic)

    Science.gov (United States)

    Foroutan-Rad, Masoud; Tappeh, Khosrow Hazrati; Khademvatan, Shahram

    2015-01-01

    Leishmaniasis is caused by an obligate intracellular protozoa belonging to Leishmania genus. The current drugs for treatment of leishmaniasis possess many disadvantages; therefore, researchers are continuously looking for the more effective and safer drugs. The aim of this study is to review the effectiveness, toxicities, and possible mechanisms of pharmaceutical actions of different garlic extracts and organosulfur compounds isolated from garlic against Leishmania spp. in a variety of in vitro, in vivo and clinical trials reports. All relevant databases were searched using the terms “Allium sativum,” “Garlic,” “Allicin,” “Ajoene,” “Leishmania,” “in vitro,” “in vivo,” and “clinical trial,” alone or in combination from 5 English databases (Web of Science, PubMed, Science Direct, Scopus, Google Scholar) and 3 Persian databases (Scientific Information Database, Iran Medex, and Magiran) from 1990 to 2014. In summary, garlic with immunomodulatory effects and apoptosis induction contributes to the treatment of leishmaniasis. PMID:26721553

  2. Immunomodulatory nutraceuticals with potential clinical use for dogs and cats

    Directory of Open Access Journals (Sweden)

    Leandro Zaine

    2014-09-01

    Full Text Available The use of nutraceuticals in veterinary medicine is growing and is assumed that they could aid in clinical treatment. This review aims to describe some nutraceuticals that act on the immunity of dogs and cats and show the possible benefits as an adjuvant treatment for some diseases. The action of some yeast derivates as immunomodulators, especially the beta-glucan fraction, was already proved to occur in dogs and cats, being beneficial as an adjuvant therapy in many clinical conditions. Omega-3 polyunsatured fatty acids, possibly the mostly used nutraceuticals, can improve the condition in some diseases, such as hypertension, renal, cardiac, gastrointestinal and autoimmune diseases, arthritis and cancer. Vitamin E has antioxidant and immunomodulatory action and can aid in the treatment of dermatologic and hepatobiliar conditions. The use of carotenoids, which have similar action to vitamin E, can be of interest for being potent antioxidants and might be helpful for enhancing immune response against microorganisms and also act preventing tumors. Despite it are still needed clinical trials to better understand the real benefits of nutraceuticals supplementation in each specific disease, the comprehension of the mechanisms by which they act indicates they are promising for clinical use.

  3. [Uveitis associated with juvenile idiopathic arthritis : Optimization of immunomodulatory therapy].

    Science.gov (United States)

    Heiligenhaus, A; Tappeiner, C; Walscheid, K; Heinz, C

    2016-05-01

    Uveitis associated with juvenile idiopathic arthritis (JIA-associated uveitis) is a vision-threatening disorder with a high complication rate. Besides early diagnosis within screening programs an adequate therapy is essential for improvement of the long-term prognosis. Corticosteroid therapy is often insufficient. In addition to conventional immunosuppression, immunomodulatory drugs, so-called biologicals, are novel highly effective treatment modalities. A systematic search of the literature was carried out for biologicals currently used in the treatment of JIA-associated uveitis. Review of current publications, summary of treatment guidelines and discussion of treatment options for therapy refractive patients. In accordance with the current recommendations tumor necrosis factor (TNF) inhibitors are administered if uveitis inactivity cannot be achieved with topical corticosteroids and in the next stage with immunosuppressants (methotrexate preferred). According to the currently available data adalimumab is then preferred. When the effectiveness of TNF inhibitors ceases during long-term administration and/or recurrences, other biological response modifiers are attractive treatment options (e. g. lymphocyte inhibitors or specific receptor antagonists). The TNF inhibitors are of major importance for the treatment of JIA-associated uveitis. Prospective studies and registries would be desirable in order to be able to compare the value of TNF inhibitors and other biologicals and for optimization of treatment recommendations.

  4. Immunomodulatory interplay of the microbiome and therapy of rheumatic diseases.

    Science.gov (United States)

    Ostrov, Barbara E; Amsterdam, Daniel

    2017-11-01

    Modulation of the immune system by microbes, especially from the gastrointestinal tract, is increasingly considered a key factor in the onset, course and outcome of rheumatic diseases. The interplay of the microbiome, along with genetic predisposition and environmental exposure, is thought to be an important trigger for rheumatic diseases. Improved identification of the relationship of disease-specific genetic alterations and rheumatic diseases has potential diagnostic and therapeutic applications. Treatment of rheumatic disorders is influenced by microbial actions but this interplay can be challenging due to variable and unpredictable responses to therapies. Expanded knowledge of the microbiome now allows clinicians to more precisely select ideal medication regimens and to predict response to and toxicity from drugs. Rheumatic diseases and associated therapies were among the earliest microbiome interactions investigated, yet it is notable that current research is focused on clinical and immunological associations but, in comparison, a limited number of studies regarding the microbiome's impact on treatment for rheumatic diseases have been published. In the coming years, further knowledge of immunomodulating interactions between the microbiome and the immune system will aid our understanding of autoimmunity and will be increasingly important in selection of therapeutic agents for patients with autoimmune and rheumatic diseases. In this review, recent literature regarding the bidirectional immunomodulatory effects of the microbiome with rheumatic diseases and current understanding and gaps regarding the drug-microbiome interface in the management of these disorders is presented.

  5. Purification, characterization and immunomodulatory activity of polysaccharides from stem lettuce.

    Science.gov (United States)

    Nie, Chenzhipeng; Zhu, Peilei; Ma, Shuping; Wang, Mingchun; Hu, Youdong

    2018-05-15

    Stem lettuce has a long history of cultivation in China and possesses high nutritional and medicinal value. In our previous studies, extraction optimization, characterization, and bioactivities of stem lettuce polysaccharides (SLP) were investigated. In this study, SLP were further separated into two purified polysaccharides, SLP-1 and SLP-2, by anion exchange chromatography followed by size exclusion chromatography. SLP-1, with a molecular weight of 90 KDa, was mainly composed of galacturonic acid, galactose and arabinose in a molar ratio of 17.6:41.7:33.9. SLP-2, with a molecular weight of 44 KDa, was mainly composed of mannose, galacturonic acid, galactose and arabinose in a molar ratio of 11.5:69.5:9.3:8.2. In addition, both purified polysaccharides contain sulphate radicals, have triple helical structures and can promote macrophage proliferation without cytotoxicity. SLP-2 was better able to stimulate phagocytic and nitric oxide production than SLP-1. The results suggest that polysaccharides from stem lettuce could be explored as immunomodulatory agents in the field of pharmaceuticals and functional foods. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Antimicrobial and immunomodulatory activities of PR-39 derived peptides.

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    Edwin J A Veldhuizen

    Full Text Available The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics.

  7. Antimicrobial and Immunomodulatory Activities of PR-39 Derived Peptides

    Science.gov (United States)

    Veldhuizen, Edwin J. A.; Schneider, Viktoria A. F.; Agustiandari, Herfita; van Dijk, Albert; Tjeerdsma-van Bokhoven, Johanna L. M.; Bikker, Floris J.; Haagsman, Henk P.

    2014-01-01

    The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal) amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics. PMID:24755622

  8. Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

    Science.gov (United States)

    Milo, Ron

    2015-04-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

  9. Immunomodulatory activity and partial characterisation of polysaccharides from Momordica charantia.

    Science.gov (United States)

    Deng, Yuan-Yuan; Yi, Yang; Zhang, Li-Fang; Zhang, Rui-Fen; Zhang, Yan; Wei, Zhen-Cheng; Tang, Xiao-Jun; Zhang, Ming-Wei

    2014-08-29

    Momordica charantia Linn. is used as an edible and medicinal vegetable in sub-tropical areas. Until now, studies on its composition and related activities have been confined to compounds of low molecular mass, and no data have been reported concerning the plant's polysaccharides. In this work, a crude polysaccharide of M. charantia (MCP) fruit was isolated by hot water extraction and then purified using DEAE-52 cellulose anion-exchange chromatography to produce two main fractions MCP1 and MCP2. The immunomodulatory effects and physicochemical characteristics of these fractions were investigated in vitro and in vivo. The results showed that intragastric administration of 150 or 300 mg·kg-·d⁻¹ of MCP significantly increased the carbolic particle clearance index, serum haemolysin production, spleen index, thymus index and NK cell cytotoxicity to normal control levels in cyclophosphamide (Cy)-induced immunosuppressed mice. Both MCP1 and MCP2 effectively stimulated normal and concanavalin A-induced splenic lymphocyte proliferation in vitro at various doses. The average molecular weights of MCP1 and MCP2, which were measured using high-performance gel permeation chromatography, were 8.55×10⁴ Da and 4.41×10⁵ Da, respectively. Both fractions exhibited characteristic polysaccharide bands in their Fourier transform infrared spectrum. MCP1 is mainly composed of glucose and galactose, and MCP2 is mainly composed of glucose, mannose and galactose. The results indicate that MCP and its fractions have good potential as immunotherapeutic adjuvants.

  10. Immunomodulatory Activity and Partial Characterisation of Polysaccharides from Momordica charantia

    Directory of Open Access Journals (Sweden)

    Yuan-Yuan Deng

    2014-08-01

    Full Text Available Momordica charantia Linn. is used as an edible and medicinal vegetable in sub-tropical areas. Until now, studies on its composition and related activities have been confined to compounds of low molecular mass, and no data have been reported concerning the plant’s polysaccharides. In this work, a crude polysaccharide of M. charantia (MCP fruit was isolated by hot water extraction and then purified using DEAE-52 cellulose anion-exchange chromatography to produce two main fractions MCP1 and MCP2. The immunomodulatory effects and physicochemical characteristics of these fractions were investigated in vitro and in vivo. The results showed that intragastric administration of 150 or 300 mg·kg−·d−1 of MCP significantly increased the carbolic particle clearance index, serum haemolysin production, spleen index, thymus index and NK cell cytotoxicity to normal control levels in cyclophosphamide (Cy-induced immunosuppressed mice. Both MCP1 and MCP2 effectively stimulated normal and concanavalin A-induced splenic lymphocyte proliferation in vitro at various doses. The average molecular weights of MCP1 and MCP2, which were measured using high-performance gel permeation chromatography, were 8.55 × 104 Da and 4.41 × 105 Da, respectively. Both fractions exhibited characteristic polysaccharide bands in their Fourier transform infrared spectrum. MCP1 is mainly composed of glucose and galactose, and MCP2 is mainly composed of glucose, mannose and galactose. The results indicate that MCP and its fractions have good potential as immunotherapeutic adjuvants.

  11. In vitro pyrogen test for toxic or immunomodulatory drugs.

    Science.gov (United States)

    Daneshian, Mardas; Guenther, Armin; Wendel, Albrecht; Hartung, Thomas; von Aulock, Sonja

    2006-06-30

    Pyrogenic contaminations of some classes of injectable drugs, e.g. toxic or immunomodulatory as well as false-positive drugs, represent a major risk which cannot yet be excluded due to the limitations of current tests. Here we describe a modification of the In vitro Pyrogen Test termed AWIPT (Adsorb, Wash, In vitro Pyrogen Test), which addresses this problem by introducing a pre-incubation step in which pyrogenic contaminations in the test sample are adsorbed to albumin-coated beads. After rinsing, the beads are incubated with human whole blood and the release of the endogenous pyrogen interleukin-1beta is measured as a marker of pyrogenic activity. Intentional contaminations with lipopolysaccharide were retrieved from the chemotherapeutic agents paclitaxel, cisplatin and liposomal daunorubicin, the antibiotic gentamicin, the antifungal agent liposomal amphotericin B, and the corticosteroid prednisolone at lower dilutions than in the standard in vitro pyrogen test. This represents a promising new approach for the detection of pyrogenic contamination in drugs or in drugs containing interfering additives and should lead to improved safety levels.

  12. Antibody constant region peptides can display immunomodulatory activity through activation of the Dectin-1 signalling pathway.

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    Elena Gabrielli

    Full Text Available We previously reported that a synthetic peptide with sequence identical to a CDR of a mouse monoclonal antibody specific for difucosyl human blood group A exerted an immunomodulatory activity on murine macrophages. It was therapeutic against systemic candidiasis without possessing direct candidacidal properties. Here we demonstrate that a selected peptide, N10K, putatively deriving from the enzymatic cleavage of the constant region (Fc of human IgG(1, is able to induce IL-6 secretion and pIkB-α activation. More importantly, it causes an up-regulation of Dectin-1 expression. This leads to an increased activation of β-glucan-induced pSyk, CARD9 and pIkB-α, and an increase in the production of pro-inflammatory cytokines such as IL-6, IL-12, IL-1β and TNF-α. The increased activation of this pathway coincides with an augmented phagocytosis of non opsonized Candida albicans cells by monocytes. The findings suggest that some Fc-peptides, potentially deriving from the proteolysis of immunoglobulins, may cause an unexpected immunoregulation in a way reminiscent of innate immunity molecules.

  13. Immunomodulatory role for membrane vesicles released by THP-1 macrophages and respiratory pathogens during macrophage infection.

    Science.gov (United States)

    Volgers, Charlotte; Benedikter, Birke J; Grauls, Gert E; Savelkoul, Paul H M; Stassen, Frank R M

    2017-11-13

    During infection, inflammation is partially driven by the release of mediators which facilitate intercellular communication. Amongst these mediators are small membrane vesicles (MVs) that can be released by both host cells and Gram-negative and -positive bacteria. Bacterial membrane vesicles are known to exert immuno-modulatory and -stimulatory actions. Moreover, it has been proposed that host cell-derived vesicles, released during infection, also have immunostimulatory properties. In this study, we assessed the release and activity of host cell-derived and bacterial MVs during the first hours following infection of THP-1 macrophages with the common respiratory pathogens non-typeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Using a combination of flow cytometry, tunable resistive pulse sensing (TRPS)-based analysis and electron microscopy, we demonstrated that the release of MVs occurs by both host cells and bacteria during infection. MVs released during infection and bacterial culture were found to induce a strong pro-inflammatory response by naive THP-1 macrophages. Yet, these MVs were also found to induce tolerance of host cells to secondary immunogenic stimuli and to enhance bacterial adherence and the number of intracellular bacteria. Bacterial MVs may play a dual role during infection, as they can both trigger and dampen immune responses thereby contributing to immune defence and bacterial survival.

  14. Intrinsic Immunomodulatory Effects of Low-Digestible Carbohydrates Selectively Extend Their Anti-Inflammatory Prebiotic Potentials

    Directory of Open Access Journals (Sweden)

    Jérôme Breton

    2015-01-01

    Full Text Available The beneficial effects of carbohydrate-derived fibers are mainly attributed to modulation of the microbiota, increased colonic fermentation, and the production of short-chain fatty acids. We studied the direct immune responses to alimentary fibers in in vitro and in vivo models. Firstly, we evaluated the immunomodulation induced by nine different types of low-digestible fibers on human peripheral blood mononuclear cells. None of the fibers tested induced cytokine production in baseline conditions. However, only one from all fibers almost completely inhibited the production of anti- and proinflammatory cytokines induced by bacteria. Secondly, the impact of short- (five days and long-term (three weeks oral treatments with selected fibers was assessed in the trinitrobenzene-sulfonic acid colitis model in mice. The immunosuppressive fiber significantly reduced levels of inflammatory markers over both treatment periods, whereas a nonimmunomodulatory fiber had no effect. The two fibers did not differ in terms of the observed fermentation products and colonic microbiota after three weeks of treatment, suggesting that the anti-inflammatory action was not related to prebiotic properties. Hence, we observed a direct effect of a specific fiber on the murine immune system. This intrinsic, fiber-dependent immunomodulatory potential may extend prebiotic-mediated protection in inflammatory bowel disease.

  15. Cochlear implantation in autistic children with profound sensorineural hearing loss.

    Science.gov (United States)

    Lachowska, Magdalena; Pastuszka, Agnieszka; Łukaszewicz-Moszyńska, Zuzanna; Mikołajewska, Lidia; Niemczyk, Kazimierz

    2016-11-19

    Cochlear implants have become the method of choice for the treatment of severe-to-profound hearing loss in both children and adults. Its benefits are well documented in the pediatric and adult population. Also deaf children with additional needs, including autism, have been covered by this treatment. The aim of this study was to assess the benefits from cochlear implantation in deafened children with autism as the only additional disability. This study analyzes data of six children. The follow-up time was at least 43 months. The following data were analyzed: medical history, reaction to music and sound, Ling's six sounds test, onomatopoeic word test, reaction to spoken child's name, response to requests, questionnaire given to parents, sound processor fitting sessions and data. After cochlear implantation each child presented other communication skills. In some children, the symptoms of speech understanding were observed. No increased hyperactivity associated with daily use cochlear implant was observed. The study showed that in autistic children the perception is very important for a child's sense of security and makes contact with parents easier. Our study showed that oral communication is not likely to be a realistic goal in children with cochlear implants and autism. The implantation results showed benefits that varied among those children. The traditional methods of evaluating the results of cochlear implantation in children with autism are usually insufficient to fully assess the functional benefits. These benefits should be assessed in a more comprehensive manner taking into account the limitations of communication resulting from the essence of autism. It is important that we share knowledge about these complex children with cochlear implants. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  16. Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells: Characterization of Cellular Responses and Identification of Molecular Determinants

    Directory of Open Access Journals (Sweden)

    Valérie Rodrigues

    2018-01-01

    Full Text Available The tropical bont tick, Amblyomma variegatum, is a tick species of veterinary importance and is considered as one of major pest of ruminants in Africa and in the Caribbean. It causes direct skin lesions, transmits heartwater, and reactivates bovine dermatophilosis. Tick saliva is reported to affect overall host responses through immunomodulatory and anti-inflammatory molecules, among other bioactive molecules. The general objective of this study was to better understand the role of saliva in interaction between the Amblyomma tick and the host using cellular biology approaches and proteomics, and to discuss its impact on disease transmission and/or activation. We first focused on the immuno-modulating effects of semi-fed A. variegatum female saliva on bovine peripheral blood mononuclear cells (PBMC and monocyte-derived macrophages in vitro. We analyzed its immuno-suppressive properties by measuring the effect of saliva on PBMC proliferation, and observed a significant decrease in ConA-stimulated PBMC lymphoproliferation. We then studied the effect of saliva on bovine macrophages using flow cytometry to analyze the expression of MHC-II and co-stimulation molecules (CD40, CD80, and CD86 and by measuring the production of nitric oxide (NO and pro- or anti-inflammatory cytokines. We observed a significant decrease in the expression of MHC-II, CD40, and CD80 molecules, associated with decreased levels of IL-12-p40 and TNF-α and increased level of IL-10, which could explain the saliva-induced modulation of NO. To elucidate these immunomodulatory effects, crude saliva proteins were analyzed using proteomics with an Orbitrap Elite mass spectrometer. Among the 336 proteins identified in A. variegatum saliva, we evidenced bioactive molecules exhibiting anti-inflammatory, immuno-modulatory, and anti-oxidant properties (e.g., serpins, phospholipases A2, heme lipoprotein. We also characterized an intriguing ubiquitination complex that could be involved in

  17. Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells: Characterization of Cellular Responses and Identification of Molecular Determinants

    Science.gov (United States)

    Rodrigues, Valérie; Fernandez, Bernard; Vercoutere, Arthur; Chamayou, Léo; Andersen, Alexandre; Vigy, Oana; Demettre, Edith; Seveno, Martial; Aprelon, Rosalie; Giraud-Girard, Ken; Stachurski, Frédéric; Loire, Etienne; Vachiéry, Nathalie; Holzmuller, Philippe

    2018-01-01

    The tropical bont tick, Amblyomma variegatum, is a tick species of veterinary importance and is considered as one of major pest of ruminants in Africa and in the Caribbean. It causes direct skin lesions, transmits heartwater, and reactivates bovine dermatophilosis. Tick saliva is reported to affect overall host responses through immunomodulatory and anti-inflammatory molecules, among other bioactive molecules. The general objective of this study was to better understand the role of saliva in interaction between the Amblyomma tick and the host using cellular biology approaches and proteomics, and to discuss its impact on disease transmission and/or activation. We first focused on the immuno-modulating effects of semi-fed A. variegatum female saliva on bovine peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages in vitro. We analyzed its immuno-suppressive properties by measuring the effect of saliva on PBMC proliferation, and observed a significant decrease in ConA-stimulated PBMC lymphoproliferation. We then studied the effect of saliva on bovine macrophages using flow cytometry to analyze the expression of MHC-II and co-stimulation molecules (CD40, CD80, and CD86) and by measuring the production of nitric oxide (NO) and pro- or anti-inflammatory cytokines. We observed a significant decrease in the expression of MHC-II, CD40, and CD80 molecules, associated with decreased levels of IL-12-p40 and TNF-α and increased level of IL-10, which could explain the saliva-induced modulation of NO. To elucidate these immunomodulatory effects, crude saliva proteins were analyzed using proteomics with an Orbitrap Elite mass spectrometer. Among the 336 proteins identified in A. variegatum saliva, we evidenced bioactive molecules exhibiting anti-inflammatory, immuno-modulatory, and anti-oxidant properties (e.g., serpins, phospholipases A2, heme lipoprotein). We also characterized an intriguing ubiquitination complex that could be involved in saliva

  18. Bacterial infections in cynomolgus monkeys given small molecule immunomodulatory antagonists.

    Science.gov (United States)

    Price, Karen D

    2010-01-01

    Opportunistic infections (OIs) during the course of non-clinical toxicity studies can serve as a clinical indicator of immunosuppression. In monkeys, severity may be magnified since the possibility for fecal-oral and cage-to-cage transmission of bacteria exists, reserve capacity is low, and clinical signs of infection are not easily detected until the infectious process is well underway. This review summarizes a case study presented at the HESI-ILSI ITC-Sponsored workshop on Naturally Occurring Infections in Non-human Primates and Immunotoxicity Implications. It gives an overview on the impact of bacterial infections in monkeys on the development and regulatory assessment of three closely-related representative small molecule immunomodulatory (anti-inflammatory) drug candidates all inhibiting the same drug target. The infections, which sometimes progressed to bacteremia and death, originally manifested in the skin, upper respiratory tract, gastrointestinal tract, and less frequently as soft tissue abscesses. Infections were sporadic and not observed in all studies despite coverage of equivalent or higher systemic exposures or longer durations of treatment. To address concerns regarding inconsistency in the presentation and type of findings and their potential relationship to infection, steps were taken to identify causative agents (via culture, microscopy), implement various intervention and treatment regimens (supportive care, antibiotics, drug holiday), demonstrate reversibility of clinical and immune effects, and study major immune components/mechanisms affected (cytokine/stress protein profiling, immune cell phenotyping, and humoral/innate immune cell function tests). Appropriate diagnosis and characterization of the infection was critical to discrimination of these findings as a secondary pharmacologic effect rather than a direct drug-related target organ effect, and also guided clinical protocol design and regulatory acceptance.

  19. Alpinone exhibited immunomodulatory and antiviral activities in Atlantic salmon.

    Science.gov (United States)

    Valenzuela, Beatriz; Rodríguez, Felipe E; Modak, Brenda; Imarai, Mónica

    2018-03-01

    In this study, we seek to identify flavonoids able to regulate the gene expression of a group of cytokines important for the control of infections in Atlantic salmon (Salmo salar). Particularly, we studied the potential immunomodulatory effects of two flavonoids, Alpinone and Pinocembrine, which were isolated and purified from resinous exudates of Heliotropium huascoense and Heliotropium sinuatum, respectively. The transcript levels of TNF-α and IL-1 (inflammatory cytokines), IFN-γ and IL-12 (T helper 1 type cytokines), IL4/13A (Th2-type cytokine), IL-17 (Th17 type cytokine) TGF-β1 (regulatory cytokine) and IFN-α (antiviral cytokine) were quantified by qRT-PCR in kidneys of flavonoid-treated and control fish. We demonstrated that the administration of a single intramuscular dose of purified Alpinone increased the transcriptional expression of five cytokines, named TNF-α, IL-1, IFN-α, IFN-γ and TGF-β1 in treated fish compared to untreated fish. Conversely, administration of purified Pinocembrine reduced the transcriptional expression of TNF-α, IL-1 and IL-12 in the kidney of treated fish. No other changes were observed. Interestingly, Alpinone also induced in vitro antiviral effects against Infectious Salmon Anaemia virus. Results showed that Alpinone but not Pinocembrine induces the expression of cytokines, which in vertebrates are essential to control viral infections while Pinocembrine reduces pro-inflammatory cytokines. Altogether results suggest that Alpinone is a good candidate to be further tested as immunostimulant and antiviral drug. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Immunomodulatory therapy in refractory/recurrent ovarian cancer.

    Science.gov (United States)

    Chen, Chao-Yu; Lai, Chyong-Huey; Yang, Lan-Yan; Tang, Yun-Hsin; Chou, Hung-Hsueh; Chang, Chee-Jen; Lin, Cheng-Tao

    2015-04-01

    To investigate the efficacy and toxicity of immunomodulatory therapy (IMT) alone or as an add-on to palliative/salvage chemotherapy in patients with refractory/recurrent epithelial ovarian cancer (EOC). We retrospectively analyzed the efficacy and toxicity of IMT in 15 patients with refractory/recurrent EOC who had previously received multiple chemotherapy regimens. The median age of the patients was 56 years (range, 41-75 years). Three patients were platinum-sensitive, two were platinum-resistant, and the remaining 10 patients were refractory to platinum-based front-line chemotherapy. IMT consisted of picibanil (OK-432) on Day 1, interleukin-2 and/or interferon-α on Day 2 administered by subcutaneous injection (every week or 2-weekly). Five patients never received metronomic oral cyclophosphamide. After IMT, three patients achieved partial remission (PR, lasting for 11 months, ≥ 12 months, and 16 months), and six patients had stable disease (SD). The disease stabilizing rate (PR+SD) was 60% (3/3 in platinum-sensitive and 6/12 in platinum-resistant/refractory patients). The absolute lymphocyte count (ALC) at 1 month after IMT was significantly higher in the PR+SD group (median 1242.0/μL) than in the progression group (median 325.0/μL) (p = 0.012). No ≥ Grade 3 toxicities were observed. The median post-IMT survival time was 12 months (range, 2-39 months). IMT alone or add-on to palliative/salvage chemotherapy for refractory/recurrent EOC achieves a substantial disease stabilizing rate without severe toxicity, which might be a potential option in selected patients. The ALC 1 month after IMT could be an early indicator to disease stabilization. Copyright © 2015. Published by Elsevier B.V.

  1. Immunomodulatory effects of Sceletium tortuosum (Trimesemine™) elucidated in vitro: Implications for chronic disease.

    Science.gov (United States)

    Bennett, Amber C; Smith, Carine

    2018-03-25

    Sceletium tortuosum, among other Sceletium species, was traditionally used by the Khoisan people of Southern Africa for relief of pain-related ailments. However, the commercial availability of this supplement has greatly expanded due to anecdotal claims of its mood-elevating and anxiolytic properties. Unrelated research has elucidated a significant link between cytokines and the mediation of depression. Therefore, the effect of Sceletium supplementation on immune cell functionality is of interest, since the efficacy of potential depression treatments could, at least in part, rely on downregulation of pro-inflammatory signalling. The current study evaluated the immunomodulatory effects of a Sceletium extract, both basally and in the context of acute endotoxin stimulation. Primary human monocytes were supplemented with either a 0.01mg/ml or 1mg/ml Sceletium extract dose, with or without E. coli LPS stimulation in vitro, for 24h. Mitochondrial viability, as an indirect measure of cytotoxicity, and cytokine release in response to the treatment intervention were assessed. Sceletium extract treatment was associated with increased mitochondrial viability, as well as up-regulated IL-10 release under basal conditions. LPS exposure significantly decreased mitochondrial viability, but this was prevented completely under Sceletium-treated conditions. The acute inflammatory response to LPS stimulation was not negatively affected. Sceletium treatment conferred most significant effects at a dose of 0.01mg/ml. Sceletium exerts significant cytoprotective effects in the setting of endotoxin stimulation. Cytokine assessment indicated that Sceletium possesses mild anti-inflammatory properties, but does not hinder the mounting of an adequate immune response to acute immune challenge. These findings indicate that Sceletium may be beneficial for the attenuation of cytokine-induced depression, as well as in systemic low-grade inflammation. Copyright © 2017 Elsevier B.V. All rights

  2. Increased Paracrine Immunomodulatory Potential of Mesenchymal Stromal Cells in Three-Dimensional Culture

    DEFF Research Database (Denmark)

    Follin, Bjarke; Juhl, Morten; Cohen, Smadar

    2016-01-01

    Mesenchymal stromal/stem cells (MSCs) have been investigated extensively through the past years, proving to have great clinical therapeutic potential. In vitro cultivation of MSCs in three-dimensional (3D) culture systems, such as scaffolds, hydrogels, or spheroids, have recently gained attention...... for tissue engineering applications. Studies on MSC spheroids demonstrated that such cultivation increased the paracrine immunomodulatory potential of the MSCs, accompanied by phenotypic alterations. In this review, we gather results from recent experimental studies on the immunomodulatory abilities of MSCs...... when cultured as spheroids or in biomaterials like scaffolds or hydrogels compared to regular two-dimensional (2D) culture and show that alterations occurring to MSCs in spheroids also occur in MSCs in biomaterials. We provide a brief description of known mechanisms of MSC immunomodulatory capacity...

  3. Evaluation of immunomodulatory activity of “Shirishavaleha”–An Ayurvedic compound formulation in albino rats

    Science.gov (United States)

    Yadav, Shyamlal Singh; Galib; Prajapati, P. K.; Ashok, B. K.; Ravishankar, B.

    2011-01-01

    The immunomodulatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth), i.e., Twak (Bark) and Sara (Heartwood) as main ingredients was evaluated for humoral antibody formation and cell-mediated immunity in established experimental models. The study used Wistar rats of either sex weighing 200 ± 40 g, while the test drug was administered orally at a dose of 1.8 g/kg. Hemagglutination titer and body weight were recorded to assess effects on humoral immunity; immunological paw edema was assessed for cell-mediated immunity. Shirishavaleha prepared from heartwood shows significant enhancement in antibody formation, attenuation of body weight changes, and suppression of immunological paw edema, while Shirishavaleha prepared from bark shows weak immunomodulatory activity. The study therefore concludes that Shirishavaleha prepared from heartwood has significant immunomodulatory activity. PMID:22253509

  4. Evaluation of immunomodulatory activity of " Shirishavaleha"-An Ayurvedic compound formulation in albino rats

    Directory of Open Access Journals (Sweden)

    Shyamlal Singh Yadav

    2011-01-01

    Full Text Available The immunomodulatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth, i.e., Twak (Bark and Sara (Heartwood as main ingredients was evaluated for humoral antibody formation and cell-mediated immunity in established experimental models. The study used Wistar rats of either sex weighing 200 ± 40 g, while the test drug was administered orally at a dose of 1.8 g/kg. Hemagglutination titer and body weight were recorded to assess effects on humoral immunity; immunological paw edema was assessed for cell-mediated immunity. Shirishavaleha prepared from heartwood shows significant enhancement in antibody formation, attenuation of body weight changes, and suppression of immunological paw edema, while Shirishavaleha prepared from bark shows weak immunomodulatory activity. The study therefore concludes that Shirishavaleha prepared from heartwood has significant immunomodulatory activity.

  5. Evaluation of immunomodulatory activity of "Shirishavaleha"-An Ayurvedic compound formulation in albino rats.

    Science.gov (United States)

    Yadav, Shyamlal Singh; Galib; Prajapati, P K; Ashok, B K; Ravishankar, B

    2011-10-01

    The immunomodulatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth), i.e., Twak (Bark) and Sara (Heartwood) as main ingredients was evaluated for humoral antibody formation and cell-mediated immunity in established experimental models. The study used Wistar rats of either sex weighing 200 ± 40 g, while the test drug was administered orally at a dose of 1.8 g/kg. Hemagglutination titer and body weight were recorded to assess effects on humoral immunity; immunological paw edema was assessed for cell-mediated immunity. Shirishavaleha prepared from heartwood shows significant enhancement in antibody formation, attenuation of body weight changes, and suppression of immunological paw edema, while Shirishavaleha prepared from bark shows weak immunomodulatory activity. The study therefore concludes that Shirishavaleha prepared from heartwood has significant immunomodulatory activity.

  6. The immunomodulatory activities of licorice polysaccharides (Glycyrrhiza uralensis Fisch.) in CT 26 tumor-bearing mice.

    Science.gov (United States)

    Ayeka, Peter Amwoga; Bian, YuHong; Githaiga, Peter Mwitari; Zhao, Ying

    2017-12-15

    The increasing use of complementary and alternative medicine (CAM) has kindled the need for scientific evaluation of the mechanism of action of CAMs. Although, licorice, a common ingredient in many Traditional Chinese medicine (TCM) has attracted great attention for its antitumor and immunomodulatory activities, the mechanism of action of its polysaccharides is still unclear. Here we report the immunomodulatory activity of licorice polysaccharides in vivo. The differential anticancer activities of licorice polysaccharides by tumorigenesis and immunomodulation was evaluated in vivo. Six weeks old, 120 CT-26 tumor bearing BALB/c mice, weighing 20 ± 2 g were used. They were randomly divided into six groups, three groups receiving high molecular weight (fraction A), low molecular weight (fraction B) polysaccharides and crude extract (fraction C); positive, negative and normal groups receiving cytoxin, saline and normal diet respectively. Weight of mice and tumors was determined and tumorigenicity assay calculated to determine the anticancer effects. Immunomodulatory potential was determined by immune organ indices, immune cell population and serum cytokine levels using immune organ weight and index, flow cytometry and cytokine/chemokine bead panel kit respectively. Licorice polysaccharides exhibited immunomodulatory activities in CT 26 tumor bearing BALB/c mice. The polysaccharides significantly suppressed tumor growth and increased immune organ index. Furthermore, the immunomodulatory effect was evident with activation of CD4 + and CD8 + immune cells population. The polysaccharides also affected the production of various cytokines, by increasing IL 2, IL 6, IL 7 levels and a decreasing TNFα levels. In summary, licorice polysaccharide especially of low molecular weight exhibit anticancer and immunomodulatory activities by suppressing tumor growth and improving general health of mice. They also augment the thymus/spleen index and population of T lymphocytes

  7. Characterization of onion lectin (Allium cepa agglutinin) as an immunomodulatory protein inducing Th1-type immune response in vitro.

    Science.gov (United States)

    Prasanna, Vaddi K; Venkatesh, Yeldur P

    2015-06-01

    Onion (Allium cepa), a bulb crop of economic importance, is known to have many health benefits. The major objective of the present study is to address the immunomodulatory properties of onion lectin (A. cepa agglutinin; ACA). ACA was purified from onion extract by D-mannose-agarose chromatography (yield: ~1 mg/kg). ACA is non-glycosylated and showed a molecular mass of ~12 kDa under reducing/non-reducing SDS-PAGE; glutaraldehyde cross-linking indicated that ACA is a non-covalent tetramer of ~12 kDa subunits. Its N-terminal sequence (RNVLLNNEGL; UniProt KB Accn. C0HJM8) showed 70-90% homology to mannose-specific Allium agglutinins. ACA showed specific hemagglutination activity of 8200 units/mg and is stable in the pH range 6-10 and up to 45° C. The immunomodulatory activity of ACA was assessed using the macrophage cell line, RAW264.7 and rat peritoneal macrophages; at 0.1 μg/well, it showed a significant increase (6-8-fold vs. control) in the production of nitric oxide at 24h, and significantly stimulated (2-4-fold vs. control) the production of pro-inflammatory cytokines (TNF-α and IL-12) at 24h. ACA (0.1 μg/well) enhanced the proliferation of murine thymocytes by ~4 fold (vs. control) at 24h; however, ACA does not proliferate B cell-enriched rat splenocytes. Further, it significantly elevated the expression levels of cytokines (IFN-γ and IL-2) over the control in murine thymocytes. Taken together, purified ACA induces a Th1-type immune response in vitro. Though present in low amounts, ACA may contribute to the immune-boosting potential of the popular spice onion since considerable amounts are consumed on a daily basis universally. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. A Replication to Increase Happiness Indices among Some People with Profound Multiple Disabilities.

    Science.gov (United States)

    Ivancic, Martin T.; And Others

    1997-01-01

    The happiness indices in a Fun Time activity were systematically increased for three of four people with profound multiple disabilities by providing their preferred stimuli. The fourth showed decreased unhappiness. However, three people with profound disabilities and minimal movement failed to show any indices of happiness or unhappiness.…

  9. Teaching Individuals with Profound Multiple Disabilities to Access Preferred Stimuli with Multiple Microswitches

    Science.gov (United States)

    Tam, Gee May; Phillips, Katrina J.; Mudford, Oliver C.

    2011-01-01

    We replicated and extended previous research on microswitch facilitated choice making by individuals with profound multiple disabilities. Following an assessment of stimulus preferences, we taught 6 adults with profound multiple disabilities to emit 2 different responses to activate highly preferred stimuli. All participants learnt to activate…

  10. Recognition of TLR2 N-Glycans: Critical Role in ArtinM Immunomodulatory Activity

    Science.gov (United States)

    da Silva, Thiago Aparecido; Ruas, Luciana Pereira; Nohara, Lilian L.; de Almeida, Igor Correia; Roque-Barreira, Maria Cristina

    2014-01-01

    TLR2 plays a critical role in the protection against Paracoccidioides brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and dendritic cells, which accounts for the T helper1 immunity that results from ArtinM administration. We examined the direct interaction of ArtinM with TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1 or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF-κB activation and interleukin (IL)-8 production in cells transfected with TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that had been captured by specific antibodies from a macrophages lysate. Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre-incubated with mannotriose. The biological relevance of the direct interaction of ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than macrophages from wild-type mice. Pre-treatment of murine macrophages with pharmacological inhibitors of signaling molecules demonstrated the involvement of p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2 heterodimers in a carbohydrate recognition-dependent manner and functions as a TLR2 agonist with immunomodulatory properties. PMID:24892697

  11. Recognition of TLR2 N-glycans: critical role in ArtinM immunomodulatory activity.

    Directory of Open Access Journals (Sweden)

    Vania Sammartino Mariano

    Full Text Available TLR2 plays a critical role in the protection against Paracoccidioides brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and dendritic cells, which accounts for the T helper1 immunity that results from ArtinM administration. We examined the direct interaction of ArtinM with TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1 or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF-κB activation and interleukin (IL-8 production in cells transfected with TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that had been captured by specific antibodies from a macrophages lysate. Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre-incubated with mannotriose. The biological relevance of the direct interaction of ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than macrophages from wild-type mice. Pre-treatment of murine macrophages with pharmacological inhibitors of signaling molecules demonstrated the involvement of p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2 heterodimers in a carbohydrate recognition-dependent manner and functions as a TLR2 agonist with immunomodulatory properties.

  12. Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers.

    Science.gov (United States)

    García-Honduvilla, Natalio; Cifuentes, Alberto; Ortega, Miguel A; Pastor, Marta; Gainza, Garazi; Gainza, Eusebio; Buján, Julia; Álvarez-Mon, Melchor

    2018-04-01

    Wound healing is a complex process that can be severely impaired due to pathological situations such as diabetes mellitus. Diabetic foot ulcers are a common complication of this pathology and are characterized by an excessive inflammatory response. In this work, the effects of local treatment with recombinant human epidermal growth factor (rhEGF) were studied using a full-thickness wound healing model in streptozotocin-induced diabetic rats. Wound healing process was assessed with different concentrations of rhEGF (0.1, 0.5, 2.0 and 8.0 µg/mL), placebo and both diabetic and non-diabetic controls ( n  = 53). The macroscopic healing observed in treated diabetic rats was affected by rhEGF concentration. Histologically, we also observed an improvement in the epithelialization, granulation tissue formation and maturation in treated groups, finding again the best response at doses of 0.5 and 2.0 µg/mL. Afterwards, the tissue immune response over time was assessed in diabetic rats using the most effective concentrations of rhEGF (0.5 and 2.0 µg/mL), compared to controls. The presence of macrophages, CD4 + T lymphocytes and CD8 + T lymphocytes, in the reparative tissue was quantified, and cytokine expression was measured by quantitative real-time PCR. rhEGF treatment caused a reduction in the number of infiltrating macrophages in the healing tissue of diabetic, as well as diminished activation of these leukocytes. These findings show that local administration of rhEGF improves the healing process of excisional wounds and the quality of the neoformed tissue in a dose-dependent manner. Besides, this treatment reduces the local inflammation associated with diabetic healing, indicating immuno-modulatory properties. © 2018 The authors.

  13. Characterization and Immunomodulatory Effects of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells.

    Directory of Open Access Journals (Sweden)

    Keith A Russell

    Full Text Available Mesenchymal stromal cells (MSC hold promise for both cell replacement and immune modulation strategies owing to their progenitor and non-progenitor functions, respectively. Characterization of MSC from different sources is an important and necessary step before clinical use of these cells is widely adopted. Little is known about the biology and function of canine MSC compared to their mouse or human counterparts. This knowledge-gap impedes development of canine evidence-based MSC technologies.We hypothesized that canine adipose tissue (AT and bone marrow (BM MSC (derived from the same dogs will have similar differentiation and immune modulatory profiles. Our objectives were to evaluate progenitor and non-progenitor functions as well as other characteristics of AT- and BM-MSC including 1 proliferation rate, 2 cell surface marker expression, 3 DNA methylation levels, 4 potential for trilineage differentiation towards osteogenic, adipogenic, and chondrogenic cell fates, and 5 immunomodulatory potency in vitro.1 AT-MSC proliferated at more than double the rate of BM-MSC (population doubling times in days for passage (P 2, AT: 1.69, BM: 3.81; P3, AT: 1.80, BM: 4.06; P4, AT: 2.37, BM: 5.34; P5, AT: 3.20, BM: 7.21. 2 Canine MSC, regardless of source, strongly expressed cell surface markers MHC I, CD29, CD44, and CD90, and were negative for MHC II and CD45. They also showed moderate expression of CD8 and CD73 and mild expression of CD14. Minor differences were found in expression of CD4 and CD34. 3 Global DNA methylation levels were significantly lower in BM-MSC compared to AT-MSC. 4 Little difference was found between AT- and BM-MSC in their potential for adipogenesis and osteogenesis. Chondrogenesis was poor to absent for both sources in spite of adding varying levels of bone-morphogenic protein to our standard transforming growth factor (TGF-β3-based induction medium. 5 Immunomodulatory capacity was equal regardless of cell source when tested in

  14. Immunomodulatory potencies of isolated compounds from Crataegus azarolus through their antioxidant activities.

    Science.gov (United States)

    Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Sassi, Aicha; Abed, Besma; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2016-06-01

    The search of natural immunomodulatory agents has become an area of great interest in order to reduce damage to the human body. In this study, the immunomodulatory potential of Crataegus azarolus and its isolated hyperoside on mouse lymphocytes and macrophages in vitro was assessed. The effect of C. azarolus natural compounds on splenocytes proliferation, natural killer (NK) and cytotoxic T lymphocytes (CTL) activities, and on macrophage-mediated cytotoxicity were assessed by MTT test. Phagocytic activity and inhibition of nitric oxide (NO) release by macrophages were also evaluated. The antioxidant capacity of these products was evaluated by determining their cellular antioxidant activity (CAA) in splenocytes and macrophages. Depending on the concentrations, both ethyl acetate (EA) extract and hyperoside (Hyp) from C. azarolus affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide release. Whereas, the above-mentioned products significantly promote LPS and lectin-stimulated splenocyte proliferation, implying a potential activation of lymphocytes B and T enhancing humoral and cellular immune responses. Moreover, EA extract and Hyp could enhance the activity of NK and T lymphocytes cells, as well as the macrophages-mediated cytotoxicity against B16F10 cells. The anti-inflammatory activity was concomitant with the cellular antioxidant effect of the tested compounds against macrophages and splenocytes. Collectively, C. azarolus and its isolated hyperoside exhibited an immunomodulatory effect through their antioxidant activity. These findings suggest that C. azarolus should be explored as a novel potential immunomodulatory agent for the treatment of inflammatory diseases.

  15. Anti-Inflammatory and Immunomodulatory Mechanism of Tanshinone IIA for Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Zhuo Chen

    2014-01-01

    Full Text Available Tanshinone IIA (Tan II A is widely used in the treatment of cardiovascular diseases as an active component of Salvia miltiorrhiza Bunge. It has been demonstrated to have pleiotropic effects for atherosclerosis. From the anti-inflammatory and immunomodulatory mechanism perspective, this paper reviewed major progresses of Tan IIA in antiatherosclerosis research, including immune cells, antigens, cytokines, and cell signaling pathways.

  16. Misperceiving Bullshit as Profound Is Associated with Favorable Views of Cruz, Rubio, Trump and Conservatism.

    Directory of Open Access Journals (Sweden)

    Stefan Pfattheicher

    Full Text Available The present research investigates the associations between holding favorable views of potential Democratic or Republican candidates for the US presidency 2016 and seeing profoundness in bullshit statements. In this contribution, bullshit is used as a technical term which is defined as communicative expression that lacks content, logic, or truth from the perspective of natural science. We used the Bullshit Receptivity scale (BSR to measure seeing profoundness in bullshit statements. The BSR scale contains statements that have a correct syntactic structure and seem to be sound and meaningful on first reading but are actually vacuous. Participants (N = 196; obtained via Amazon Mechanical Turk rated the profoundness of bullshit statements (using the BSR and provided favorability ratings of three Democratic (Hillary Clinton, Martin O'Malley, and Bernie Sanders and three Republican candidates for US president (Ted Cruz, Marco Rubio, and Donald Trump. Participants also completed a measure of political liberalism/conservatism. Results revealed that favorable views of all three Republican candidates were positively related to judging bullshit statements as profound. The smallest correlation was found for Donald Trump. Although we observe a positive association between bullshit and support for the three Democrat candidates, this relationship is both substantively small and statistically insignificant. The general measure of political liberalism/conservatism was also related to judging bullshit statements as profound in that individuals who were more politically conservative had a higher tendency to see profoundness in bullshit statements. Of note, these results were not due to a general tendency among conservatives to see profoundness in everything: Favorable views of Republican candidates and conservatism were not significantly related to profoundness ratings of mundane statements. In contrast, this was the case for Hillary Clinton and Martin O

  17. Misperceiving Bullshit as Profound Is Associated with Favorable Views of Cruz, Rubio, Trump and Conservatism.

    Science.gov (United States)

    Pfattheicher, Stefan; Schindler, Simon

    2016-01-01

    The present research investigates the associations between holding favorable views of potential Democratic or Republican candidates for the US presidency 2016 and seeing profoundness in bullshit statements. In this contribution, bullshit is used as a technical term which is defined as communicative expression that lacks content, logic, or truth from the perspective of natural science. We used the Bullshit Receptivity scale (BSR) to measure seeing profoundness in bullshit statements. The BSR scale contains statements that have a correct syntactic structure and seem to be sound and meaningful on first reading but are actually vacuous. Participants (N = 196; obtained via Amazon Mechanical Turk) rated the profoundness of bullshit statements (using the BSR) and provided favorability ratings of three Democratic (Hillary Clinton, Martin O'Malley, and Bernie Sanders) and three Republican candidates for US president (Ted Cruz, Marco Rubio, and Donald Trump). Participants also completed a measure of political liberalism/conservatism. Results revealed that favorable views of all three Republican candidates were positively related to judging bullshit statements as profound. The smallest correlation was found for Donald Trump. Although we observe a positive association between bullshit and support for the three Democrat candidates, this relationship is both substantively small and statistically insignificant. The general measure of political liberalism/conservatism was also related to judging bullshit statements as profound in that individuals who were more politically conservative had a higher tendency to see profoundness in bullshit statements. Of note, these results were not due to a general tendency among conservatives to see profoundness in everything: Favorable views of Republican candidates and conservatism were not significantly related to profoundness ratings of mundane statements. In contrast, this was the case for Hillary Clinton and Martin O'Malley. Overall, small

  18. Immunomodulatory Effects of Macrolide Antibiotics - Part 1 : Biological Mechanisms

    NARCIS (Netherlands)

    Altenburg, J.; de Graaff, C. S.; van der Werf, T. S.; Boersma, W. G.

    2011-01-01

    Macrolide antibiotics are well known for their antibacterial and anti-inflammatory properties. This article provides an overview of the biological mechanisms through which macrolides exert this 'double effect'. Their antibacterial effect consists of the inhibition of bacterial protein synthesis,

  19. Reversal of profound rocuronium neuromuscular blockade by sugammadex in anesthetized rhesus monkeys.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the

  20. Immunomodulatory Effects of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03, Alone and in Combination, on Peripheral Blood Mononuclear Cells of Allergic Asthmatics.

    Science.gov (United States)

    Drago, Lorenzo; De Vecchi, Elena; Gabrieli, Arianna; De Grandi, Roberta; Toscano, Marco

    2015-07-01

    The aim of this study was to evaluate probiotic characteristics of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03 alone and in combination and their immunomodulatory activity in asthmatic subjects. Subjects affected by allergic asthma were recruited. Initially, LS01 and BR03 were analyzed for their growth compatibility by a broth compatibility assay. To study the antimicrobial activity of probiotic strains, an agar diffusion assay was performed. Finally, cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with LS01 and BR03 was determined by means of specific quantitative enzyme-linked immunosorbent assay (ELISA). The growth of some clinical pathogens were slightly inhibited by LS01 and LS01-BR03 co-culture supernatant not neutralized to pH 6.5, while only the growth of E. coli and S. aureus was inhibited by the supernatant of LS01 and LS01-BR03 neutralized to pH 6.5. Furthermore, LS01 and BR03 combination was able to decrease the secretion of proinflammatory cytokines by PBMCs, leading to an intense increase in IL-10 production. L. salivarius LS01 and B. breve BR03 showed promising probiotic properties and beneficial immunomodulatory activity that are increased when the 2 strains are used in combination in the same formulation.

  1. Immunomodulatory Activity and Protective Effects of Polysaccharide from Eupatorium adenophorum Leaf Extract on Highly Pathogenic H5N1 Influenza Infection

    Directory of Open Access Journals (Sweden)

    Yi Jin

    2013-01-01

    Full Text Available The development of novel broad-spectrum, antiviral agents against H5N1 infection is urgently needed. In this study, we evaluated the immunomodulatory activities and protective effect of Eupatorium adenophorum polysaccharide (EAP against the highly pathogenic H5N1 subtype influenza virus. EAP treatment significantly increased the production of IL-6, TNF-α, and IFN-γ both in vivo and in vitro as measured by qPCR and ELISA. In a mouse infection model, intranasal administration of EAP at a dose of 25 mg/kg body weight prior to H5N1 viral challenge efficiently inhibited viral replication, decreased lung lesions, and increased survival rate. We further evaluated the innate immune recognition of EAP, as this process is regulated primarily Dectin-1 and mannose receptor (MR. These results indicate that EAP may have immunomodulatory properties and a potential prophylactic effect against H5N1 influenza infection. Our investigation suggests an alternative strategy for the development of novel antiinfluenza agents and benefits of E. adenophorum products.

  2. Anti-herpes simplex virus 1 and immunomodulatory activities of a poly-γ- glutamic acid from Bacillus horneckiae strain APA of shallow vent origin.

    Science.gov (United States)

    Marino-Merlo, Francesca; Papaianni, Emanuela; Maugeri, Teresa L; Zammuto, Vincenzo; Spanò, Antonio; Nicolaus, Barbara; Poli, Annarita; Di Donato, Paola; Mosca, Claudia; Mastino, Antonio; Gugliandolo, Concetta

    2017-10-01

    Herpes simplex virus type 1 (HSV-1) is responsible of common and widespread viral infections in humans through the world, and of rare, but extremely severe, clinical syndromes in the central nervous system. The emergence of resistant strains to drugs actually in use encourages the searching for novel antiviral compounds, including those of natural origin. In this study, the recently described poly-γ-glutamic acid (γ-PGA-APA), produced by the marine thermotolerant Bacillus horneckiae strain APA, and previously shown to possess biological and antiviral activity, was evaluated for its anti-HSV-1 and immunomodulatory properties. The biopolymer hindered the HSV-1 infection in the very early phase of virus replication. In addition, the γ-PGA-APA was shown to exert low cytotoxicity and noticeable immunomodulatory activities towards TNF-α and IL-1β gene expression. Moreover, the capacity to positively modulate the transcriptional activity of the cytokine genes was paired with increased level of activation of the transcription factor NF-kB by γ-PGA-APA. Overall, as non-cytotoxic biopolymer able to contribute in the antiviral defense against HSV-1, γ-PGA-APA could lead to the development of novel natural drugs for alternative therapies.

  3. DMPD: Gram-negative endotoxin: an extraordinary lipid with profound effects oneukaryotic signal transduction. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 1916089 Gram-negative endotoxin: an extraordinary lipid with profound effects oneuk...ep;5(12):2652-60. (.png) (.svg) (.html) (.csml) Show Gram-negative endotoxin: an extraordinary lipid with profound effects...tive endotoxin: an extraordinary lipid with profound effects oneukaryotic signal transduction. Authors Raetz

  4. Immunomodulatory effects of OX40Ig gene-modified adipose tissue-derived mesenchymal stem cells on rat kidney transplantation

    OpenAIRE

    Liu, Tao; Zhang, Yue; Shen, Zhongyang; Zou, Xunfeng; Chen, Xiaobo; Chen, Li; Wang, Yuliang

    2016-01-01

    Recent studies have suggested that adipose tissue-derived mesenchymal stem cell (ADSC) therapy and OX40 costimulation blockade are two immunomodulatory strategies used to suppress the immune response to alloantigens. However, relatively little has been reported regarding the immunomodulatory potential of the abilityof these two strategies to synergize. Thus, in the present study, we aimed to investigate OX40-Ig fusion protein (OX40Ig) expression in ADSCs and to validate their more potent immu...

  5. Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

    Directory of Open Access Journals (Sweden)

    Rodrigo Rezende Kitagawa

    2011-12-01

    Full Text Available Large number of quinones has been associated with antitumor, antibacterial, antimalarial and antifungal activities. In this work we describe the effect of the naphthoquinone, 5-methoxy-3,4-dehydroxanthomegnin, on murine tumor cells (LP07 and LM2 and its immunomodulatory effect on nitric oxide (NO production on LPS-stimulated macrophages. The results have shown that 5-methoxy-3,4-dehydroxanthomegnin was a significant inhibitor of LPS-stimulated NO generation from macrophage (inhibition percentage ranged from 97.4 to 98.9% and a strong cytotoxic agent against both tumor cells LP07 and LM2 (CI50 6.2±0.36 µM and 74.6±1.9 µM, respectively. These results indicate that the 5-methoxy-3,4-dehydroxanthomegnin may show promising activity in the treatment of murine breast and lung cancer by immunomodulatory and antiproliferative activities.

  6. Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

    Directory of Open Access Journals (Sweden)

    Rodrigo Rezende Kitagawa

    2011-08-01

    Full Text Available Large number of quinones has been associated with antitumor, antibacterial, antimalarial and antifungal activities. In this work we describe the effect of the naphthoquinone, 5-methoxy-3,4-dehydroxanthomegnin, on murine tumor cells (LP07 and LM2 and its immunomodulatory effect on nitric oxide (NO production on LPS-stimulated macrophages. The results have shown that 5-methoxy-3,4-dehydroxanthomegnin was a significant inhibitor of LPS-stimulated NO generation from macrophage (inhibition percentage ranged from 97.4 to 98.9% and a strong cytotoxic agent against both tumor cells LP07 and LM2 (CI50 6.2±0.36 µM and 74.6±1.9 µM, respectively. These results indicate that the 5-methoxy-3,4-dehydroxanthomegnin may show promising activity in the treatment of murine breast and lung cancer by immunomodulatory and antiproliferative activities.

  7. Experience of Using Immunomodulatory Therapy in Comprehensive Treatment of Chronic Tonsillitis in Children

    Directory of Open Access Journals (Sweden)

    Yu.V. Marushko

    2015-02-01

    Full Text Available Immunomodulatory therapy is an important part of treating patients with chronic tonsillitis caused by β-hemolytic streptococcus group A, on the background of antibiotic therapy it allows us to achieve a more effective elimination of the pathogen. Administration of Imupret in the comprehensive treatment for exacerbation of chronic tonsillitis of streptococcal origin leads to the rapid disappearance of clinical manifestations of the disease, high frequency of pathogen elimination, reduces the incidence of chronic tonsillitis exa­cerbations.

  8. Identity of the immunomodulatory proteins from garlic (Allium sativum) with the major garlic lectins or agglutinins.

    Science.gov (United States)

    Clement, Fatima; Pramod, Siddanakoppalu N; Venkatesh, Yeldur P

    2010-03-01

    Garlic (Allium sativum), an important medicinal spice, displays a plethora of biological effects including immunomodulation. Although some immunomodulatory proteins from garlic have been described, their identities are still unknown. The present study was envisaged to isolate immunomodulatory proteins from raw garlic, and examine their effects on certain cells of the immune system (lymphocytes, mast cells, and basophils) in relation to mitogenicity and hypersensitivity. Three protein components of approximately 13 kD (QR-1, QR-2, and QR-3 in the ratio 7:28:1) were separated by Q-Sepharose chromatography of 30 kD ultrafiltrate of raw garlic extract. All the 3 proteins exhibited mitogenic activity towards human peripheral blood lymphocytes, murine splenocytes and thymocytes. The mitogenicity of QR-2 was the highest among the three immunomodulatory proteins. QR-1 and QR-2 displayed hemagglutination and mannose-binding activities; QR-3 showed only mannose-binding activity. Immunoreactivity of rabbit anti-QR-1 and anti-QR-2 polyclonal antisera showed specificity for their respective antigens as well as mutual cross-reactivity; QR-3 was better recognized by anti-QR-2 (82%) than by anti-QR-1 (55%). QR-2 induced a 2-fold higher histamine release in vitro from leukocytes of atopic subjects compared to that of non-atopic subjects. In all functional studies, QR-2 was more potent compared to QR-1. Taken together, all these results indicate that the two major proteins QR-2 and QR-1 present in a ratio of 4:1 in raw garlic contribute to garlic's immunomodulatory activity, and their characteristics are markedly similar to the abundant Allium sativum agglutinins (ASA) I and II, respectively. Copyright 2010 Elsevier B.V. All rights reserved.

  9. Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

    OpenAIRE

    Heyes, Richard; Iarocci, Andrew; Tchoukalova, Yourka; Lott, David G.

    2016-01-01

    This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs) in promoting vascularized composite allotransplant (VCA) tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft) with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human popul...

  10. SCREENING OF PHYTOCHEMICALS AND IMMUNOMODULATORY POTENTIAL OF A MEDICINAL PLANT, CINNAMOMUM TAMALA

    OpenAIRE

    P. Jeyasree* and P. Dasarathan

    2012-01-01

    Cinnamomum tamala is found in tropical and sub-tropical Himalayas and in some other places. Phytochemical screening of the plant extracts were done to screen their active constituents. Antimicrobial activity of this plant extract was investigated by Kirby-Bayer methodology against four pathogenic organisms: K. Pneumonae,E. coli, S. aureus, and P.aeroginosa. The plant Butanol extract showed inhibitory activity against all the tested organisms and it has enhanced immunomodulatory activity also....

  11. ProFound: Source Extraction and Application to Modern Survey Data

    Science.gov (United States)

    Robotham, A. S. G.; Davies, L. J. M.; Driver, S. P.; Koushan, S.; Taranu, D. S.; Casura, S.; Liske, J.

    2018-05-01

    We introduce PROFOUND, a source finding and image analysis package. PROFOUND provides methods to detect sources in noisy images, generate segmentation maps identifying the pixels belonging to each source, and measure statistics like flux, size, and ellipticity. These inputs are key requirements of PROFIT, our recently released galaxy profiling package, where the design aim is that these two software packages will be used in unison to semi-automatically profile large samples of galaxies. The key novel feature introduced in PROFOUND is that all photometry is executed on dilated segmentation maps that fully contain the identifiable flux, rather than using more traditional circular or ellipse-based photometry. Also, to be less sensitive to pathological segmentation issues, the de-blending is made across saddle points in flux. We apply PROFOUND in a number of simulated and real-world cases, and demonstrate that it behaves reasonably given its stated design goals. In particular, it offers good initial parameter estimation for PROFIT, and also segmentation maps that follow the sometimes complex geometry of resolved sources, whilst capturing nearly all of the flux. A number of bulge-disc decomposition projects are already making use of the PROFOUND and PROFIT pipeline, and adoption is being encouraged by publicly releasing the software for the open source R data analysis platform under an LGPL-3 license on GitHub (github.com/asgr/ProFound).

  12. A Prognostic Model for Development of Profound Shock among Children Presenting with Dengue Shock Syndrome.

    Directory of Open Access Journals (Sweden)

    Phung Khanh Lam

    Full Text Available To identify risk factors and develop a prediction model for the development of profound and recurrent shock amongst children presenting with dengue shock syndrome (DSS.We analyzed data from a prospective cohort of children with DSS recruited at the Paediatric Intensive Care Unit of the Hospital for Tropical Disease in Ho Chi Minh City, Vietnam. The primary endpoint was "profound DSS", defined as ≥2 recurrent shock episodes (for subjects presenting in compensated shock, or ≥1 recurrent shock episodes (for subjects presenting initially with decompensated/hypotensive shock, and/or requirement for inotropic support. Recurrent shock was evaluated as a secondary endpoint. Risk factors were pre-defined clinical and laboratory variables collected at the time of presentation with shock. Prognostic model development was based on logistic regression and compared to several alternative approaches.The analysis population included 1207 children of whom 222 (18% progressed to "profound DSS" and 433 (36% had recurrent shock. Independent risk factors for both endpoints included younger age, earlier presentation, higher pulse rate, higher temperature, higher haematocrit and, for females, worse hemodynamic status at presentation. The final prognostic model for "profound DSS" showed acceptable discrimination (AUC=0.69 for internal validation and calibration and is presented as a simple score-chart.Several risk factors for development of profound or recurrent shock among children presenting with DSS were identified. The score-chart derived from the prognostic models should improve triage and management of children presenting with DSS in dengue-endemic areas.

  13. Isolation of immunomodulatory triterpene acids from a standardized rose hip powder (Rosa canina L.).

    Science.gov (United States)

    Saaby, Lasse; Jäger, Anna Katharina; Moesby, Lise; Hansen, Erik Wind; Christensen, Søren Brøgger

    2011-02-01

    A previously published systematic review and a metaanalysis have concluded that the consumption of standardized rose hip powder (Rosa canina L.) can reduce pain in osteoarthritis patients. Synovial inflammation has been suggested to play an important role in the pathogenesis of osteoarthritis and mainly to involve infiltration of the synovial membrane by macrophages. Therefore, the immunomodulatory effect of standardized rose hip powder of Rosa canina L. was investigated and active principles isolated using the Mono Mac 6 cell line as a model for human macrophages. Treatment of Mono Mac 6 cells with the residue of a crude dichloromethane extract of rose hip powder significantly and concentration dependently inhibited the lipopolysaccharide induced interleukin-6 release. Through bioassay-guided fractionation the immunomodulatory effect of the dichloromethane extract was correlated to a mixture of three triterpene acids; oleanolic acid, betulinic acid and ursolic acid (IC(50) 21 ± 6 µm). Further studies revealed that only oleanolic acid and ursolic acid, but not betulinic acid, could inhibit the lipopolysaccharide induced interleukin-6 release from Mono Mac 6 cells when tested separately. Combination of either oleanolic acid or ursolic acid with betulinic acid enhanced the immunomodulatory effect of the two triterpene acids. Copyright © 2010 John Wiley & Sons, Ltd.

  14. Immunomodulatory potential of Anacyclus pyrethrum (L.) and Mucuna pruriens (L.) In male albino rats.

    Science.gov (United States)

    Yousaf, F; Shahid, M; Riaz, M; Atta, A; Fatima, H

    2017-01-01

    The present study was designed to investigate the immunomodulatory potential of Anacyclus pyrethrum roots and Mucuna pruriens seeds in male albino rats. The roots of A. pyrethrum and seeds of M. pruriens were extracted with methanolic solvent (70:30) and administered at dose concentrations of 50, 100 and 200 mg/Kg body weight to healthy male rats. The immune system of rats was suppressed by injecting carbon tetrachloride to animals in the toxic control group and test group animals. Cell-mediated immune response of animals was examined by performing neutrophil adhesion test and the humoral immune response was evaluated by determining serum immunoglobulin levels of the animals under study. The administration of methanolic extracts of A. pyrethrum roots and M. pruriens seeds significantly (p less than 0.05) increased the neutrophil adhesion to the nylon fiber. Increase in % neutrophil adhesion was observed in animals treated with 200 mg of each plant extract. Significant (p less than 0.05) improvement in immunoglobulin levels was recorded in the extract treated group animals, showing that the root extract of A. pyrethrum and seed extract of M. pruriens have immunomodulatory potential. We therefore conclude that the tested extracts can be used as immunomodulatory agents to stimulate the immune system.

  15. In vitro and in vivo mechanism of immunomodulatory and antiviral activity of Edible Bird's Nest (EBN) against influenza A virus (IAV) infection.

    Science.gov (United States)

    Haghani, Amin; Mehrbod, Parvaneh; Safi, Nikoo; Aminuddin, Nur Ain; Bahadoran, Azadeh; Omar, Abdul Rahman; Ideris, Aini

    2016-06-05

    For centuries, Edible Bird Nest (EBN) has been used in treatment of variety of respiratory diseases such as flu and cough as a Chinese natural medicine. This natural remedy showed the potential to inhibit influenza A virus (IAV). However, little is known about the mechanism of this process and also the evaluation of this product in an animal model. Hence, the current study was designed to elucidate the antiviral and immunomodulatory effects of EBN against IAV strain A/Puerto Rico/8/1934 (H1N1). First, influenza infected MDCK cells treated with EBNs from two locations of Malaysia (Teluk Intan and Gua Madai) that prepared with different enzymatic preparations were analyzed by RT-qPCR and ELISA for detection of viral and cytokines genes. The sialic acid composition of these EBNs was evaluated by H-NMR. Subsequently, after toxicity evaluation of EBN from Teluk Intan, antiviral and immunomodulatory effects of this natural product was evaluated in BALB/c mice by analysis of the viral NA gene and cytokine expressions in the first week of the infection. EBN showed high neuraminidase inhibitory properties in both in vitro and in vivo, which was as effective as Oseltamivir phosphate. In addition, EBN decreased NS1 copy number (p<0.05) of the virus along with high immunomodulatory effects against IAV. Some of the immune changes during treatment of IAV with EBN included significant increase in IFNγ, TNFα, NFκB, IL2, some proinflammatory cytokines like IL1β, IL6, and cytokines with regulatory properties like IL10, IL27, IL12, CCL2 and IL4 depends on the stage of the infection. EBNs from two locations contained different composition of sialic acid and thymol derivatives, which gave them different antiviral properties. EBN from Gua Madai that contained more acetylated sialic acid (Neu2,4,7,8,9 Ac6) showed higher antiviral activity. The findings of this study support the antiviral activity of EBN against influenza virus and validate the traditional usage of this natural remedy

  16. Immunomodulatory Effect of Red Onion (Allium cepa Linn) Scale Extract on Experimentally Induced Atypical Prostatic Hyperplasia in Wistar Rats

    Science.gov (United States)

    Elberry, Ahmed A.; Al-Maghrabi, Jaudah; Abdel Sattar, Essam; Ghareib, Salah A.; Mosli, Hisham A.; Gabr, Salah A.

    2014-01-01

    Red onion scales (ROS) contain large amounts of flavonoids that are responsible for the reported antioxidant activity, immune enhancement, and anticancer property. Atypical prostatic hyperplasia (APH) was induced in adult castrated Wistar rats by both s.c. injection of testosterone (0.5 mg/rat/day) and by smearing citral on shaved skin once every 3 days for 30 days. Saw palmetto (100 mg/kg) as a positive control and ROS suspension at doses of 75, 150, and 300 mg/kg/day were given orally every day for 30 days. All medications were started 7 days after castration and along with testosterone and citral. The HPLC profile of ROS methanolic extract displayed two major peaks identified as quercetin and quercetin-4′-β-O-D-glucoside. Histopathological examination of APH-induced prostatic rats revealed evidence of hyperplasia and inflammation with cellular proliferation and reduced apoptosis Immunohistochemistry showed increased tissue expressions of IL-6, IL-8, TNF-α, IGF-1, and clusterin, while TGF-β1 was decreased, which correlates with the presence of inflammation. Both saw palmetto and RO scale treatment have ameliorated these changes. These ameliorative effects were more evident in RO scale groups and were dose dependent. In conclusion, methanolic extract of ROS showed a protective effect against APH induced rats that may be attributed to potential anti-inflammatory and immunomodulatory effects. PMID:24829522

  17. Immunomodulatory Effect of Red Onion (Allium cepa Linn Scale Extract on Experimentally Induced Atypical Prostatic Hyperplasia in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Ahmed A. Elberry

    2014-01-01

    Full Text Available Red onion scales (ROS contain large amounts of flavonoids that are responsible for the reported antioxidant activity, immune enhancement, and anticancer property. Atypical prostatic hyperplasia (APH was induced in adult castrated Wistar rats by both s.c. injection of testosterone (0.5 mg/rat/day and by smearing citral on shaved skin once every 3 days for 30 days. Saw palmetto (100 mg/kg as a positive control and ROS suspension at doses of 75, 150, and 300 mg/kg/day were given orally every day for 30 days. All medications were started 7 days after castration and along with testosterone and citral. The HPLC profile of ROS methanolic extract displayed two major peaks identified as quercetin and quercetin-4′-β-O-D-glucoside. Histopathological examination of APH-induced prostatic rats revealed evidence of hyperplasia and inflammation with cellular proliferation and reduced apoptosis Immunohistochemistry showed increased tissue expressions of IL-6, IL-8, TNF-α, IGF-1, and clusterin, while TGF-β1 was decreased, which correlates with the presence of inflammation. Both saw palmetto and RO scale treatment have ameliorated these changes. These ameliorative effects were more evident in RO scale groups and were dose dependent. In conclusion, methanolic extract of ROS showed a protective effect against APH induced rats that may be attributed to potential anti-inflammatory and immunomodulatory effects.

  18. Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions

    Directory of Open Access Journals (Sweden)

    Elisa Wirthgen

    2018-01-01

    Full Text Available Tryptophan metabolites are known to participate in the regulation of many cells of the immune system and are involved in various immune-mediated diseases and disorders. Kynurenic acid (KYNA is a product of one branch of the kynurenine pathway of tryptophan metabolism. The influence of KYNA on important neurophysiological and neuropathological processes has been comprehensively documented. In recent years, the link of KYNA to the immune system, inflammation, and cancer has become more apparent. Given this connection, the anti-inflammatory and immunosuppressive functions of KYNA are of particular interest. These characteristics might allow KYNA to act as a “double-edged sword.” The metabolite contributes to both the resolution of inflammation and the establishment of an immunosuppressive environment, which, for instance, allows for tumor immune escape. Our review provides a comprehensive update of the significant biological functions of KYNA and focuses on its immunomodulatory properties by signaling via G-protein-coupled receptor 35 (GPR35- and aryl hydrocarbon receptor-mediated pathways. Furthermore, we discuss the role of KYNA–GPR35 interaction and microbiota associated KYNA metabolism for gut homeostasis.

  19. Immunomodulatory/inflammatory effects of geopropolis produced by Melipona fasciculata Smith in combination with doxorubicin on THP-1 cells.

    Science.gov (United States)

    Oliveira, Lucas Pires Garcia; Conte, Fernanda Lopes; Cardoso, Eliza de Oliveira; Conti, Bruno José; Santiago, Karina Basso; Golim, Marjorie de Assis; Cruz, Maria Teresa; Sforcin, José Maurício

    2016-12-01

    Geopropolis (GEO) in combination with doxorubicin (DOX) reduced HEp-2 cells viability compared to GEO and DOX alone. A possible effect of this combination on the innate immunity could take place, and its effects were analysed on THP-1 cell - a human leukaemia monocytic cell line used as a model to study monocyte activity and macrophage activity, assessing cell viability, expression of cell markers and cytokine production. THP-1 cells were incubated with GEO, DOX and their combination. Cell viability was assessed by MTT assay, cell markers expression by flow cytometry and cytokine production by ELISA. GEO + DOX did not affect cell viability. GEO alone or in combination increased TLR-4 and CD80 but not HLA-DR and TLR-2 expression. GEO stimulated TNF-α production while DOX alone or in combination did not affect it. GEO alone or in combination inhibited IL-6 production. GEO exerted a pro-inflammatory profile by increasing TLR-4 and CD80 expression and TNF-α production, favouring the activation of the immune/inflammatory response. GEO + DOX did not affect cell viability and presented an immunomodulatory action. Lower concentrations of DOX combined to GEO could be used in cancer patients, avoiding side effects and benefiting from the biological properties of GEO. © 2016 Royal Pharmaceutical Society.

  20. Attuning: A Communication Process between People with Severe and Profound Intellectual Disability and Their Interaction Partners.

    Science.gov (United States)

    Griffiths, Colin; Smith, Martine

    2016-03-01

    People with severe and profound intellectual disability typically demonstrate a limited ability to communicate effectively. Most of their communications are non-verbal, often idiosyncratic and ambiguous. This article aims to identify the process that regulates communications of this group of people with others and to describe the methodological approach that was used to achieve this. In this qualitative study, two dyads consisting of a person with severe or profound intellectual and multiple disability and a teacher or carer were filmed as they engaged in school-based activities. Two 1-hour videotapes were transcribed and analysed using grounded theory. Attuning was identified within the theory proposed here as a central process that calibrates and regulates communication. Attuning is conceptualized as a bidirectional, dyadic communication process. Understanding this process may support more effective communication between people with severe or profound intellectual and multiple disability and their interaction partners. © 2015 John Wiley & Sons Ltd.

  1. Prevalence of Auditory Neuropathy in a Population of Children with Severe to Profound Hearing Loss

    Directory of Open Access Journals (Sweden)

    Nader Saki

    2013-04-01

    Full Text Available Background: The purpose of this investigation is to determine auditory neuropathy in the students with severe to profound hearing losses in Ahwaz.Materials and Methods: In this cross-sectional study, 212 children of 7-11 year old with severe to profound hearing loss performed ordinary audiometric evaluations as well as ABR and OAE. The patients with normal DPOAE who had no record of acoustic reflex having normal ABR, were considered as the patients with auditory neuropathy. Results: The neuropathic complication found in 14 children was appeared in 8 ones as one-sided (57.14% and in 6 ones (42.86% as two-sided. 68% of the patients as diagnosed had a very low Speech Discrimination Score (SDS.Conclusion: we must be very vigilant in auditory neuropathy diagnosis for the purpose to be successful in appropriate treatment of severe to profound hearing losses.

  2. Myelomonocytic THP-1 cells for in vitro testing of immunomodulatory properties of nanoparticles.

    Science.gov (United States)

    Schroecksnadel, Sebastian; Jenny, Marcel; Fuchs, Dietmar

    2011-02-01

    The use of nanoparticles for new therapeutic and diagnostics options represents a new risk for individuals exposed to such compounds. The myelomonocytic cell line THP-1 could be a useful alternative to human peripheral blood mononuclear cells (PBMC) to test for effects of drugs and compounds. Stimulation degree of cells can be monitored by measurement of neopterin and/or the kynurenine to tryptophan ratio. The method is robust and reproducible in the range of 0.1-1.0 microg/ml of LPS. However, compared to the PBMC assay it will not reveal any effect on the T-cell interaction.

  3. Chemical characterization and immunomodulatory properties of polysaccharides isolated from probiotic Lactobacillus casei LOCK 0919

    Czech Academy of Sciences Publication Activity Database

    Górska, S.; Hermanová, Petra; Ciekot, J.; Schwarzer, Martin; Šrůtková, Dagmar; Brzozowska, E.; Kozáková, Hana; Gamian, A.

    2016-01-01

    Roč. 26, č. 9 (2016), s. 1014-1024 ISSN 0959-6658 Institutional support: RVO:61388971 Keywords : immunomodulation * Lactobacillus * NMR spectroscopy Subject RIV: EE - Microbiology, Virology Impact factor: 3.112, year: 2016

  4. Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells.

    Science.gov (United States)

    Deuse, Tobias; Stubbendorff, Mandy; Tang-Quan, Karis; Phillips, Neil; Kay, Mark A; Eiermann, Thomas; Phan, Thang T; Volk, Hans-Dieter; Reichenspurner, Hermann; Robbins, Robert C; Schrepfer, Sonja

    2011-01-01

    We here present an immunologic head-to-head comparison between human umbilical cord lining mesenchymal stem cells (clMSCs) and adult bone marrow MSCs (bmMSCs) from patients >65 years of age. clMSCs had significantly lower HLA class I expression, higher production of tolerogenic TGF-β and IL-10, and showed significantly faster proliferation. In vitro activation of allogeneic lymphocytes and xenogeneic in vivo immune activation was significantly stronger with bmMSCs, whereas immune recognition of clMSCs was significantly weaker. Thus, bmMSCs were more quickly rejected in immunocompetent mice. IFN-γ at 25 ng/ml increased both immunogenicity by upregulation of HLA class I/ HLA-DR expression and tolerogenicity by increasing intracellular HLA-G and surface HLA-E expression, augmenting TGF-β and IL-10 release, and inducing indoleamine 2,3-dioxygenase (IDO) expression. Higher concentrations of IFN-γ (>50 ng/ml) further enhanced the immunosuppressive phenotype of clMSCs, more strongly downregulating HLA-DR expression and further increasing IDO production (at 500 ng/ml). The net functional immunosuppressive efficacy of MSCs was tested in mixed lymphocyte cultures. Although both clMSCs and bmMSCs significantly reduced in vitro immune activation, clMSCs were significantly more effective than bmMSCs. The veto function of both MSC lines was enhanced in escalating IFN-γ environments. In conclusion, clMSCs show a more beneficial immunogeneic profile and stronger overall immunosuppressive potential than aged bmMSCs.

  5. Immunomodulatory properties of subcellular fractions of a G+ bacterium, Bacillus firmus

    Czech Academy of Sciences Publication Activity Database

    Čechová, D.; Nováková, M.; Mikulík, Karel; Novotná, O.; Julák, J.; Zanvit, P.; Prokešová, L.

    2013-01-01

    Roč. 58, č. 2 (2013), s. 111-121 ISSN 0015-5632 Grant - others:GA ČR(CZ) GA310/07/0675 Institutional support: RVO:61388971 Keywords : TOXIN-B SUBUNIT * INFLUENZA-VIRUS * INTRANASAL IMMUNIZATION Subject RIV: EE - Microbiology, Virology Impact factor: 1.145, year: 2013

  6. The immunomodulatory properties of probiotic microorganisms beyond their viability (ghost probiotics: proposal of paraprobiotic concept)

    OpenAIRE

    Taverniti, Valentina; Guglielmetti, Simone

    2011-01-01

    The probiotic approach represents a potentially effective and mild alternative strategy for the prevention and treatment of either inflammatory or allergic diseases. Several studies have shown that different bacterial strains can exert their probiotic abilities by influencing the host’s immune system, thereby modulating immune responses. However, the emerging concern regarding safety problems arising from the extensive use of live microbial cells is enhancing the interest in non-viable microo...

  7. Immunomodulatory properties of Concholepas concholepas hemocyanin against francisellosis in a zebrafish model

    OpenAIRE

    Lagos, Leidy; Tandberg, Julia Isabel; Becker, María Inés; Winther-Larsen, Hanne Cecilie

    2017-01-01

    The development of vaccines for aquaculture has been an important milestone in providing a continuous and sustainable production. Most of the vaccines currently on the market for aquaculture include oil as adjuvant. Nevertheless, several studies reported an occurrence of side effects after their use in farmed fish. As a result, there is a need for new and improved adjuvants that can stimulate the immune system while causing as few side-effects as possible. Hemocyanins are versatile macromolec...

  8. Bordetella pertussis pertactin knock-out strains reveal immunomodulatory properties of this virulence factor.

    NARCIS (Netherlands)

    Hovingh, Elise Sofie; Mariman, Rob; Solans, Luis; Hijdra, Daniëlle; Hamstra, Hendrik-Jan; Jongerius, Ilse; van Gent, Marjolein; Mooi, Frits; Locht, Camille; Pinelli, Elena

    2018-01-01

    Whooping cough, caused by Bordetella pertussis, has resurged and presents a global health burden worldwide. B. pertussis strains unable to produce the acellular pertussis vaccine component pertactin (Prn), have been emerging and in some countries represent up to 95% of recent clinical isolates.

  9. Filamentous hemagglutinin of Bordetella pertussis: a key adhesin with immunomodulatory properties?

    Czech Academy of Sciences Publication Activity Database

    Romero, Rodrigo, Villarino; Osička, Radim; Šebo, Peter

    2014-01-01

    Roč. 9, č. 12 (2014), s. 1339-1360 ISSN 1746-0913 R&D Projects: GA ČR(CZ) P302/11/0580; GA ČR(CZ) GA13-14547S Institutional support: RVO:61388971 Keywords : Bordetella * adhesion * integrins * filamentous hemagglutinin Subject RIV: EE - Microbiology, Virology Impact factor: 4.275, year: 2014

  10. The immunomodulatory role of carbon monoxide during transplantation

    Directory of Open Access Journals (Sweden)

    Amano Mariane

    2013-01-01

    Full Text Available Abstract The number of organ and tissue transplants has increased worldwide in recent decades. However, graft rejection, infections due to the use of immunosuppressive drugs and a shortage of graft donors remain major concerns. Carbon monoxide (CO had long been regarded solely as a poisonous gas. Ultimately, physiological studies unveiled the endogenous production of CO, particularly by the heme oxygenase (HO-1 enzyme, recognizing CO as a beneficial gas when used at therapeutic doses. The protective properties of CO led researchers to develop uses for it, resulting in devices and molecules that can deliver CO in vitro and in vivo. The resulting interest in clinical investigations was immediate. Studies regarding the CO/HO-1 modulation of immune responses and their effects on various immune disorders gave rise to transplantation research, where CO was shown to be essential in the protection against organ rejection in animal models. This review provides a perspective of how CO modulates the immune system to improve transplantation and suggests its use as a therapy in the field.

  11. Anti-inflammatory and immunomodulatory effects of Aquaphilus dolomiae extract on in vitro models

    Directory of Open Access Journals (Sweden)

    Aries MF

    2016-11-01

    Full Text Available Marie-Françoise Aries,1 Hélène Hernandez-Pigeon,1 Clémence Vaissière,1 Hélène Delga,1 Antony Caruana,1 Marguerite Lévêque,1 Muriel Bourrain,1,2 Katia Ravard Helffer,1 Bertrand Chol,3 Thien Nguyen,1 Sandrine Bessou-Touya,1 Nathalie Castex-Rizzi1 1Pierre Fabre Dermo-Cosmétique, Centre de Recherche & Développement Pierre Fabre, Toulouse, 2Sorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes (LBBM, Observatoire Océanologique, Banyuls/Mer, France; 3Centre d’Immunologie Pierre Fabre, Saint-Julien-en-Genevois, France Background: Atopic dermatitis (AD is a common skin disease characterized by recurrent pruritic inflammatory skin lesions resulting from structural and immune defects of the skin barrier. Previous studies have shown the clinical efficacy of Avène thermal spring water in AD, and a new microorganism, Aquaphilus dolomiae was suspected to contribute to these unique properties. The present study evaluated the anti-inflammatory, antipruritic, and immunomodulatory properties of ES0, an original biological extract of A. dolomiae, in immune and inflammatory cell models in order to assess its potential use in the treatment of AD.Materials and methods: An ES0 extract containing periplasmic and membrane proteins, peptides, lipopolysaccharides, and exopolysaccharides was obtained from A. dolomiae. The effects of the extract on pruritus and inflammatory mediators and immune mechanisms were evaluated by using various AD cell models and assays.Results: In a keratinocyte model, ES0 inhibited the expression of the inflammatory mediators, thymic stromal lymphopoietin, interleukin (IL-18, IL-4R, IL-8, monocyte chemoattractant protein-3, macrophage inflammatory protein-3α, and macrophage-derived chemokine and induced the expression of involucrin, which is involved in skin barrier keratinocyte terminal differentiation. In addition, ES0 inhibited protease-activated receptor-2 activation in

  12. Classroom Procedures for the Measurement of Behavior State among Students with Profound Disabilities.

    Science.gov (United States)

    Guy, Barbara; And Others

    1993-01-01

    This study examined whether teacher-implemented classroom measurement procedures of short duration are as reliable as methods used in research studies to determine behavior state (e.g., awake active, awake inactive, asleep, drowsed) of six students with profound mental disabilities. Results indicated that more frequent but briefer measurements…

  13. The Role of Sound in Residential Facilities for People With Profound Intellectual and Multiple Disabilities

    NARCIS (Netherlands)

    van den Bosch, Kirsten A.; Andringa, Tjeerd C.; Baskent, Deniz; Vlaskamp, Carla

    2016-01-01

    Attention to the auditory environment of people with profound intellectual and multiple disabilities (PIMD) is limited, both in research and practice. As there is a dynamic interplay between the quality of the auditory environment and well-being, a study was undertaken to test the validity of the

  14. The Influence of Phonological Mechanisms in Written Spelling of Profoundly Deaf Children

    Science.gov (United States)

    Colombo, Lucia; Arfe, Barbara; Bronte, Tiziana

    2012-01-01

    In the present study, the effect of phonological and working memory mechanisms involved in spelling Italian single words was explored in two groups of children matched for grade level: a group of normally hearing children and a group of pre-verbally deaf children, with severe-to-profound hearing loss. Three-syllable and four-syllable familiar…

  15. Self-Concept of Severely to Profoundly Hearing-Impaired Children.

    Science.gov (United States)

    Warren, Charlotte; Hasenstab, Suzanne

    1986-01-01

    A study examined demographic, impairment-related, and parental variables that best predicted self-concept among 49 severely to profoundly hearing-impaired 5- to 11-year-olds. A strong relationship was observed between self-concept and parental indulgence, parental rejection, parental protection, parental discipline, and extent of language…

  16. A Data Based Multidimensional Oral Hygiene Curriculum for the Severely and Profoundly Handicapped.

    Science.gov (United States)

    Feldman, David; Elliott, Thomas A.

    A multidimensional oral hygiene curriculum appropriate for the moderately to profoundly retarded and composed of tooth brushing, flossing, and gum stimulation/massage is proposed. Task analyses are included for manual tooth brushing, utilizing an oral irrigation appliance, manual flossing, and use of an adaptive aid for flossing. Also provided are…

  17. Operationalizing quality of life for people with profound multiple disabilities : a Delphi study

    NARCIS (Netherlands)

    Petry, K.; Maes, B.; Vlaskamp, C.

    Background: In a recent study, we constructed an item pool that contains items on the quality of life (QOL) and related aspects of support of people with profound multiple disabilities (PMD). In the present study, a panel of experts assessed the content and the structure of this item pool in order

  18. The Curriculum for Children with Severe and Profound Learning Difficulties at Stephen Hawking School

    Science.gov (United States)

    Rayner, Matthew

    2011-01-01

    The increasing number of children with profound and multiple learning difficulties means that many schools for children with severe learning difficulties are having to review the curriculum that they offer. In addition, these schools are continuing to question whether a subject-based approach, in line with the National Curriculum, is the most…

  19. Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Booij, L.H.D.J.; Driessen, J.J.

    2009-01-01

    A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and

  20. Connections that Count: Brain-Computer Interface Enables the Profoundly Paralyzed to Communicate

    Science.gov (United States)

    ... Home Current Issue Past Issues Connections that Count: Brain-Computer Interface Enables the Profoundly Paralyzed to Communicate Past Issues / ... of this page please turn Javascript on. A brain-computer interface (BCI) system This brain-computer interface (BCI) system ...

  1. A Preliminary Investigation of the Suitability of Aquatics for People with Severe and Profound Intellectual Disabilities

    Science.gov (United States)

    Aherne, Cian; Coughlan, Barry

    2017-01-01

    Background: Aquatics is an under-researched but possibly appropriate form of activity for people with severe to profound intellectual disabilities (SPIDs). Aim: The current pilot study investigates the suitability of an aquatics programme for service users with SPIDs. Method: Four service users with SPID completed an 8-12-session aquatics…

  2. Determining alertness in individuals with profound intellectual and multiple disabilities : the reliability of an observation list

    NARCIS (Netherlands)

    Munde, V.S.; Vlaskamp, C.; Ruijssenaars, A.J.J.M.; Nakken, H.

    In the support of individuals with profound intellectual and multiple disabilities (PIMD), assessing the level of alertness is a recurring issue for parents and other direct support persons. Although observations show clear advantages above and beyond other assessment methods, there are problems

  3. Social Peer Interactions in Persons with Profound Intellectual and Multiple Disabilities: A Literature Review

    Science.gov (United States)

    Nijs, Sara; Maes, Bea

    2014-01-01

    Social interactions may positively influence developmental and quality of life outcomes. Research in persons with profound intellectual and multiple disabilities (PIMD) mostly investigated interactions with caregivers. This literature review focuses on peer interactions of persons with PIMD. A computerized literature search of three databases was…

  4. Normality and Impairment following Profound Early Institutional Deprivation: A Longitudinal follow-up into Early Adolescence

    Science.gov (United States)

    Kreppner, Jana M.; Rutter, Michael; Beckett, Celia; Castle, Jenny; Colvert, Emma; Groothues, Christine; Hawkins, Amanda; O'Connor, Thomas G.; Stevens, Suzanne; Sonuga-Barke, Edmund J. S.

    2007-01-01

    Longitudinal analyses on normal versus impaired functioning across 7 domains were conducted in children who had experienced profound institutional deprivation up to the age of 42 months and were adopted from Romania into U.K. families. Comparisons were made with noninstitutionalized children adopted from Romania and with nondeprived within-U.K.…

  5. The pros and cons of inclusive education for children with Profound Intellectual and Multiple Disabilities

    NARCIS (Netherlands)

    Everaarts, Sanne; de Boer, Anke; van der Putten, Annette; Minnaert, Alexander

    2016-01-01

    Aim: Although children with disabilities have the right to be included into the school system, children with Profound Intellectual and Multiple Disabilities (PIMD) are often not included. The aim of this study is to gather knowledge about inclusive education for children with PIMD by identifying

  6. Bereavement and Loss: Developing a Memory Box to Support a Young Woman with Profound Learning Disabilities

    Science.gov (United States)

    Young, Hannah; Garrard, Brenda

    2016-01-01

    Supporting bereaved people with profound learning disabilities still remains an under-researched area. Moreover, the barriers of communication and disenfranchised grief mean that they often do not receive the support they require, leading to emotional and behavioural difficulties. This article describes research using a case study design, which…

  7. Visual impairments in people with severe and profound multiple disabilities: An inventory of visual functioning

    NARCIS (Netherlands)

    van den Broek, E.G.C.; Janssen, C.G.C.; van Ramshorst, T.; Deen, L.

    2006-01-01

    Background: The prevalence of visual impairments in people with severe and profound multiple disabilities (SPMD) is the subject of considerable debate and is difficult to assess. Methods: In a typical Dutch care organization, all clients with SPMD (n = 76) participated in the study and specific

  8. Is more profound knowledge in the field of radiation nece--ssary for doctors

    International Nuclear Information System (INIS)

    Klener, V.

    1981-01-01

    Reasons are listed why doctors should have more profound knowledge in the field of radiation. Despite imperceptibility by human senses of ionizing radiation, the parameters characterizing irradiation can accurately be measured. The units of the said parameters are listed and characterized and the relationships are explained of the radiation dose and non-stochastic and stochastic radiation effects. (Ha)

  9. HEART RATE AND PHYSICAL ACTIVITY PATTERNS IN PERSONS WITH PROFOUND INTELLECTUAL AND MULTIPLE DISABILITIES

    NARCIS (Netherlands)

    Waninge, Aly; van der Putten, Annette A. J.; Stewart, Roy E.; Steenbergen, Bert; van Wijck, Ruud; van der Schans, Cees P.

    2013-01-01

    Because physical fitness and health are related to physical activity, it is important to gain an insight into the physical activity levels of persons with profound intellectual and multiple disabilities (PIMD). The purpose of this study was to examine heart rate patterns to measure the activity

  10. Attentional Processes in Interactions between People with Profound Intellectual and Multiple Disabilities and Direct Support Staff

    Science.gov (United States)

    Ine, Hostyn; Heleen, Neerinckx; Bea, Maes

    2011-01-01

    Few studies have examined joint attention in interactions with persons with profound intellectual and multiple disabilities (PIMD), despite its important role in high-quality interaction. The purpose of this study is to describe the attention-directing behaviours of persons with PIMD and their direct support staff and the attention episodes…

  11. Interaction between Persons with Profound Intellectual and Multiple Disabilities and Their Partners: A Literature Review

    Science.gov (United States)

    Hostyn, Ine; Maes, Bea

    2009-01-01

    Background: High quality interactions are of crucial importance for quality of life of persons with profound intellectual and multiple disabilities (PIMD). This literature review describes and synthesises studies addressing the interaction between persons with PIMD and their partners. Method: A computerised literature search using defined…

  12. A Vibrotactile Interface to Motivate Movement for Children with Severe to Profound Disabilities

    DEFF Research Database (Denmark)

    Manresa-Yee, Cristina; Morrison, Ann; Larsen, Jeppe Veirum

    2014-01-01

    V-Sense is a vibrotactile interface that encourages children with severe or profound cognitive, sensory and physical impairments to move. The interface makes use of touch, in particular vibrations, as a supportive function to motivate users' actions. Specifically, we propose a vibrotactile...

  13. Attuning: A Communication Process between People with Severe and Profound Intellectual Disability and Their Interaction Partners

    Science.gov (United States)

    Griffiths, Colin; Smith, Martine

    2016-01-01

    Background: People with severe and profound intellectual disability typically demonstrate a limited ability to communicate effectively. Most of their communications are non-verbal, often idiosyncratic and ambiguous. This article aims to identify the process that regulates communications of this group of people with others and to describe the…

  14. Immunomodulatory Effect of Exercise in Patients with Asthma

    Directory of Open Access Journals (Sweden)

    Seda Tural Önür

    2017-04-01

    Full Text Available Objective: Immune responses can change with exercise. We aimed to show the changes in cytokine levels pre- and post-exercise in patients with asthma. Methods: In this prospective control trial, data of 32 patients with asthma that was under control were classified into two groups, pre- and post-exercise. Serum IL-1β and monocyte IL-1β, IL-2, and IL-10 expressions were evaluated using enzyme-linked immunosorbent assay. The patients were advised to walk for at least 30 min for 4 days/week for 12 weeks. Results: There was no significant difference in demographic properties of the participants. Monocyte IL-1β levels in the pre- and post-exercise groups were 1.99±0.35 and 1.01±0.22 pg/mL, respectively (p=0.003. IL-10 levels in the pre- and post-exercise groups were 1.64±0.02 and 1.21±0.03 pg/mL, respectively (p=0.04. IL-2 levels in the pre- and post-exercise groups were 0.64±0.045 and 0.32±0.09 pg/mL, respectively (p=0.001. However, there was a significant difference in serum IL-1β and monocyte IL-1β, IL-2, and IL-10 levels between the groups (p=0.02, p=0.003, p=0.04, and p=0.001, respectively. Conclusion: Systemic inflammatory parameters that are commonly elevated in asthma may improve by exercise. The elucidation of the mechanism of immune control in patients with asthma is useful for the future treatment of asthma.

  15. A novel immunomodulatory hemocyanin from the limpet Fissurella latimarginata promotes potent anti-tumor activity in melanoma.

    Directory of Open Access Journals (Sweden)

    Sergio Arancibia

    Full Text Available Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treatment of cancer. In this study, we evaluated a novel hemocyanin from the limpet/gastropod Fissurella latimarginata (FLH. This protein has the typical hollow, cylindrical structure of other known hemocyanins, such as the keyhole limpet hemocyanin (KLH and the Concholepas hemocyanin (CCH. FLH, like the KLH isoforms, is composed of a single type of polypeptide with exposed N- and O-linked oligosaccharides. However, its immunogenicity was significantly greater than that of KLH and CCH, as FLH induced a stronger humoral immune response and had more potent anti-tumor activity, delaying tumor growth and increasing the survival of mice challenged with B16F10 melanoma cells, in prophylactic and therapeutic settings. Additionally, FLH-treated mice demonstrated increased IFN-γ production and higher numbers of tumor-infiltrating CD4(+ lymphocytes. Furthermore, in vitro assays demonstrated that FLH, but not CCH or KLH, stimulated the rapid production of pro-inflammatory cytokines (IL-6, IL-12, IL-23 and TNF-α by dendritic cells, triggering a pro-inflammatory milieu that may explain its enhanced immunological activity. Moreover, this effect was abolished when deglycosylated FLH was used, suggesting that carbohydrates play a crucial role in the innate immune recognition of this protein. Altogether, our data demonstrate that FLH possesses increased anti-tumor activity in part because it activates a more potent innate immune response in comparison to other known hemocyanins. In conclusion, FLH is a potential new marine adjuvant for immunization and possible cancer

  16. A novel immunomodulatory hemocyanin from the limpet Fissurella latimarginata promotes potent anti-tumor activity in melanoma.

    Science.gov (United States)

    Arancibia, Sergio; Espinoza, Cecilia; Salazar, Fabián; Del Campo, Miguel; Tampe, Ricardo; Zhong, Ta-Ying; De Ioannes, Pablo; Moltedo, Bruno; Ferreira, Jorge; Lavelle, Ed C; Manubens, Augusto; De Ioannes, Alfredo E; Becker, María Inés

    2014-01-01

    Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treatment of cancer. In this study, we evaluated a novel hemocyanin from the limpet/gastropod Fissurella latimarginata (FLH). This protein has the typical hollow, cylindrical structure of other known hemocyanins, such as the keyhole limpet hemocyanin (KLH) and the Concholepas hemocyanin (CCH). FLH, like the KLH isoforms, is composed of a single type of polypeptide with exposed N- and O-linked oligosaccharides. However, its immunogenicity was significantly greater than that of KLH and CCH, as FLH induced a stronger humoral immune response and had more potent anti-tumor activity, delaying tumor growth and increasing the survival of mice challenged with B16F10 melanoma cells, in prophylactic and therapeutic settings. Additionally, FLH-treated mice demonstrated increased IFN-γ production and higher numbers of tumor-infiltrating CD4(+) lymphocytes. Furthermore, in vitro assays demonstrated that FLH, but not CCH or KLH, stimulated the rapid production of pro-inflammatory cytokines (IL-6, IL-12, IL-23 and TNF-α) by dendritic cells, triggering a pro-inflammatory milieu that may explain its enhanced immunological activity. Moreover, this effect was abolished when deglycosylated FLH was used, suggesting that carbohydrates play a crucial role in the innate immune recognition of this protein. Altogether, our data demonstrate that FLH possesses increased anti-tumor activity in part because it activates a more potent innate immune response in comparison to other known hemocyanins. In conclusion, FLH is a potential new marine adjuvant for immunization and possible cancer immunotherapy.

  17. Immunomodulatory effect of Moringa peregrina leaves, ex vivo and in vivo study

    Science.gov (United States)

    Al-Oran, Sawsan Atallah; Hassuneh, Mona Rushdie; Al-Qaralleh, Haitham Naief; Rayyan, Walid Abu; Al-Thunibat, Osama Yosef; Mallah, Eyad; Abu-Rayyan, Ahmed; Salem, Shadi

    2017-01-01

    This study was conducted to assess the in vivo and ex vivo immunomodulatory effect of the ethanol leaves extract of Moringa peregrina in Balb/c mice. For this study, five groups of 5 Balb/c mice were given a single acute subtoxic oral dose of the ethanolic extract at 1.13, 11.30, 23.40 and 113.4 mg/kg and the immunomodulatory effect was assessed on the 6th day following the ingestion. In the (non-functional) assessment, the effect of the extract on the body weight, relative lymphoid organ weight, splenic cellularity and peripheral blood hematologic parameters were evaluated. While in the immunomodulation assessment (functional), we investigated the effect of the extract on the proliferative capacity of splenic lymphocytes and peripheral T and B lymphocytes using mitogen blastogenesis, mixed allogeneic MLR and IgM-Plaque forming cells assays. The ingestion of M. peregrina extract caused a significant increase in the body weight, weight and number of cells of spleen and lymph nodes of the treated mice. Furthermore, the count of RBCs, WBCs, platelets, hemoglobin concentration and PCV % were increased by the extract treatment in a dose-dependent manner. M. peregrina enhanced the proliferative responses of splenic lymphocytes for both T cell and B-cell mitogens. Likewise, the mixed lymphocyte reaction MLR assay has revealed a T-cell dependent proliferation enhancement in the extract treated mice. Moreover, the oral administration of M. peregrina leaves extracts significantly increased PFCs/106 splenocytes in a dose-dependent manner. In conclusion, subtoxic acute doses of M. peregrina extract demonstrated significant potential as an immunomodulatory agent even at the lowest dose of 1.13 mg/kg. PMID:29204086

  18. In vitro immunomodulatory potential of Artemisia indica Willd. in chicken lymphocytes

    Directory of Open Access Journals (Sweden)

    Pushpa Ruwali

    2018-01-01

    Full Text Available Aim: Evaluation of the in vitro immunomodulatory potential of Artemisia indica Willd. methanolic extract in chicken lymphocyte culture system through lymphocyte (B and T cells proliferation assay, after standardizing the maximum non-cytotoxic dose (MNCD in chicken lymphocytes. Materials and Methods: Fresh aerial parts of A. indica Willd. (family: Asteraceae specimens were collected (altitude 1560 m, gotten authenticated, processed, dried, and Soxhlet extracted to yield methanolic extract (AME. Chicken splenocytes were isolated from spleens collected from healthy birds; lymphocytes were separated by density gradient centrifugation, percentage cell viability determined and final cell count adjusted to 107 cells/ml in RPMI-1640 medium. MNCD of AME in chicken lymphocytes was determined through 3-(4,5-dimethylthiazol-2-y1-2,5-diphenyltetrazolium bromide dye reduction assay. Immunomodulatory potential of AME was evaluated through lymphocytes proliferation or B and T cells blastogenesis assay in the presence of appropriate mitogens, namely, lipopolysaccharide (LPS and concanavalin A (Con A, respectively. Results: Maximum concentration of AME exhibiting 100% cell viability (MNCD was 200 μg/ml and was selected for further in vitro analysis. The in vitro exposure of chicken lymphocytes to 200 μg/ml dose of AME, resulted in significant (p<0.05 upregulation of 11.76% in B cell proliferation in the presence of B cell mitogen (LPS and a significant (p<0.05 increase of 12.018% T cells proliferation in the presence of the mitogen (Con A, as compared to the control. Conclusion: The significant upregulation in the proliferation of two major cell types modulating the immune system is an indication of the immunostimulatory potential of the plant. It would be worthwhile to further evaluate A. indica on relevant immunomodulatory aspects, especially the in vivo studies in a poultry system.

  19. Phytochemical, chromatographic and spectroscopic investigation of Carum copticum seeds and their potential as immunomodulatory agents.

    Science.gov (United States)

    Sonar, Pankaj K; Singh, Ranjit; Saraf, Shailendra K

    2016-01-01

    Carum copticum seeds have been prescribed in the traditional system of medicine for the treatment of immune disorders, such as asthma and rheumatism. The objective of this study was to determine immunomodulatory effects of the alcoholic extract and isolated compounds in Swiss albino mice. Seeds of C. copticum were extracted with 95% v/v alcohol. The immunomodulatory activity of the crude extract was evaluated at the doses of 100, 300, and 500 mg/kg body weight of mice, administered in mice once daily (orally) for 25 days. Volatile oil of C. copticum was isolated by steam distillation and was characterized by GLC and HPLC. Bio-assay-guided fractionation and isolation were carried out and the isolated compounds were characterized and subjected to immunomodulatory activity studies. The n-hexane fraction yielded p-cymene, carvacrol, and α-pinene. The LD50 value of the crude extract was found to be 4500 mg/kg and the values reported for p-cymene, carvacrol, and α-pinene in the literature were 4750, 810, and 3700 mg/kg, respectively. The oral administration of crude extract, n-hexane fraction (HEF), and isolated oils at the dose of 500, 150, and 50 mg/kg body weight, respectively, showed a significant increase in the HA titers, DTH-response, and phagocytosis. The stimulatory effect observed, on humoral and cellular immunity, was compared with the standard (levamisole treated) and control groups. The results obtained in the study endorse the traditional use of the seeds of C. copticum and the isolated constituents act as immunostimulants.

  20. In vitro immunomodulatory potential of Artemisia indica Willd. in chicken lymphocytes.

    Science.gov (United States)

    Ruwali, Pushpa; Ambwani, Tanuj Kumar; Gautam, Pankaj

    2018-01-01

    Evaluation of the in vitro immunomodulatory potential of Artemisia indica Willd. methanolic extract in chicken lymphocyte culture system through lymphocyte (B and T cells) proliferation assay, after standardizing the maximum non-cytotoxic dose (MNCD) in chicken lymphocytes. Fresh aerial parts of A. indica Willd. (family: Asteraceae) specimens were collected (altitude 1560 m), gotten authenticated, processed, dried, and Soxhlet extracted to yield methanolic extract (AME). Chicken splenocytes were isolated from spleens collected from healthy birds; lymphocytes were separated by density gradient centrifugation, percentage cell viability determined and final cell count adjusted to 10 7 cells/ml in RPMI-1640 medium. MNCD of AME in chicken lymphocytes was determined through 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide dye reduction assay. Immunomodulatory potential of AME was evaluated through lymphocytes proliferation or B and T cells blastogenesis assay in the presence of appropriate mitogens, namely, lipopolysaccharide (LPS) and concanavalin A (Con A), respectively. Maximum concentration of AME exhibiting 100% cell viability (MNCD) was 200 μg/ml and was selected for further in vitro analysis. The in vitro exposure of chicken lymphocytes to 200 µg/ml dose of AME, resulted in significant (p<0.05) upregulation of 11.76% in B cell proliferation in the presence of B cell mitogen (LPS) and a significant (p<0.05) increase of 12.018% T cells proliferation in the presence of the mitogen (Con A), as compared to the control. The significant upregulation in the proliferation of two major cell types modulating the immune system is an indication of the immunostimulatory potential of the plant. It would be worthwhile to further evaluate A. indica on relevant immunomodulatory aspects, especially the in vivo studies in a poultry system.

  1. Antileishmanial and immunomodulatory activities of lupeol, a triterpene compound isolated from Sterculia villosa.

    Science.gov (United States)

    Das, Antu; Jawed, Junaid Jibran; Das, Manash C; Sandhu, Padmani; De, Utpal C; Dinda, Biswanath; Akhter, Yusuf; Bhattacharjee, Surajit

    2017-10-01

    Visceral leishmaniasis (VL) is one of the most severe forms of leishmaniasis, caused by the protozoan parasite Leishmania donovani. Nowadays there is a growing interest in the therapeutic use of natural products to treat parasitic diseases. Sterculia villosa is an ethnomedicinally important plant. A triterpenoid was isolated from this plant and was screened for its antileishmanial and immunomodulatory activities in vitro and in vivo. Biochemical colour test and spectroscopic data confirmed that the isolated pure compound was lupeol. Lupeol exhibited significant antileishmanial activity, with IC 50 values of 65 ± 0.41 µg/mL and 15 ± 0.45 µg/mL against promastigote and amastigote forms, respectively. Lupeol caused maximum cytoplasmic membrane damage of L. donovani promastigote at its IC 50 dose. It is well known that during infection the Leishmania parasite exerts its pathogenicity in the host by suppressing nitric oxide (NO) production and inhibiting pro-inflammatory responses. It was observed that lupeol induces NO generation in L. donovani-infected macrophages, followed by upregulation of pro-inflammatory cytokines and downregulation of anti-inflammatory cytokines. Lupeol was also found to reduce the hepatic and splenic parasite burden through upregulation of the pro-inflammatory response in L. donovani-infected BALB/c mice. Strong binding affinity of lupeol was observed for four major potential drug targets, namely pteridine reductase 1, adenine phosphoribosyltransferase, lipophosphoglycan biosynthetic protein and glycoprotein 63 of L. donovani, which also supported its antileishmanial and immunomodulatory activities. Therefore, the present study highlights the antileishmanial and immunomodulatory activities of lupeol in an in vitro and in vivo model of VL. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  2. Isolation and Characterization of Exopolysaccharide with Immunomodulatory Activity from Fermentation Broth of Morchella Conica

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    Chao-an Su

    2013-01-01

    Full Text Available Background and the purpose of this study: Mushroom polysaccharides have traditionally been used for the prevention and treatment of a multitude of disorders like infectious illnesses, cancers and various autoimmune diseases. In vitro and in vivo studies suggest that certain polysaccharides affect immune system function. Morchella conica (M. conica is a species of rare edible mushroom whose multiple medicinal functions have been proven. Thus, the objective of this study is to isolate and characterize of exopolysaccharide from submerged mycelial culture of M. conica, and to evaluate its immunomodulatory activity.MethodsA water-soluble Morchella conica Polysaccharides (MCP were extracted and isolated from the fermentation broth of M. conica through a combination of DEAE-cellulose and Sephacryl S-300 HR chromatograph. NMR and IR spectroscopy has played a developing role in identification of polysaccharide with different structure and composition from fungal and plant sources, as well as complex glycosaminoglycans of animal origin. Thus, NMR and IR spectroscopy were used to analyze the chemical structure and composition of the isolated polysaccharide. Moreover, the polysaccharide was tested for its immunomodulatory activity at different concentrations using in vitro model.ResultsThe results showed that MCP may significantly modulate nitric oxide production in macrophages, and promote splenocytes proliferation. Analysis from HPLC, infrared spectra and nuclear magnetic resonance spectroscopy showed that MCP was a homogeneous mannan with an average molecular weight of approximately 81.2 kDa. The glycosidic bond links is [rightwards arrow]6-alpha-D-Man p-(1[rightwards arrow].ConclusionThe results suggested that the extracted MCP may modulate nitric oxide production in macrophages and promote splenocytes proliferation, and it may act as a potent immunomodulatory agent.

  3. Effect of immunomodulatory therapy on the endometrial inflammatory response to induced infectious endometritis in susceptible mares

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Woodward, Elizabeth; Bojesen, Anders Miki

    2012-01-01

    endometritis based on their endometrial histopathology and ability to clear an induced uterine inflammation. To investigate the effect of immunomodulatory therapy, the mares were inoculated with 10(5) colony forming units (CFU) Escherichia coli in three consecutive estrus cycles in a modified cross-over study...... inoculation. Endometrial biopsies were recovered 3, 24 and 72 h post inoculation. Relative gene-expression analyses were performed by quantitative reverse transcriptase PCR (qRT-PCR). Endometrial gene expression of inflammatory cytokines was modulated by administration of GC. Expression of proinflammatory...

  4. Immunomodulatory effects of helminths and protozoa in multiple sclerosis and experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Hasseldam, Henrik; Hansen, C S; Johansen, F F

    2013-01-01

    hygiene standards that exist in the western world, with reduced exposure to various pathogens, including parasites, as a consequence. Parasites are known to employ various immunomodulatory and anti-inflammatory strategies, which enable them to evade destruction by the immune system. This is most likely...... one of the reasons for the disease-dampening effects, reported in numerous studies investigating parasite infections and autoimmunity. This review will focus on recent advances in the field of parasites as beneficial immunomodulators, in multiple sclerosis and the animal model experimental autoimmune...

  5. Differential immunomodulatory responses to nine polycyclic aromatic hydrocarbons applied by passive dosing

    DEFF Research Database (Denmark)

    Oostingh, Gertie J.; Smith, Kilian E. C.; Tischler, Ulrike

    2015-01-01

    Studying the effects of hydrophobic chemicals using in vitro cell based methods is hindered by the difficulty in bringing and keeping these chemicals in solution. Their effective concentrations are often lower than their nominal concentrations. Passive dosing is one approach that provides defined...... and stable dissolved concentrations during in vitro testing, and was applied to control and maintain freely dissolved concentrations of polycyclic aromatic hydrocarbons (PAHs) at levels up to their aqueous solubility limit. The immunomodulatory effects of 9 different PAHs at aqueous solubility on human...

  6. Oral Communication Development in Severe to Profound Hearing Impaired Children After Receiving Aural Habilitation

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    Soleimani Farin

    2009-10-01

    Full Text Available Communication, cognition, language, and speech are interrelated and develop together. It should come as no surprise to us that the key to intervention with deaf children is to establish, as early as possible, a functional communication system for the child and the parents. Early intervention programs need to be multidisciplinary, technologically sound and most important, it should take cognizance of the specific context (community, country in which the child and family function. The main aim of this study was to obtain oral communication development regarding current status of the intervention (aural habilitation and speech therapyfor children with severe to profound hearing impairment in Iran. A prospective longitudinal study was undertaken on a consecutive group of children with severe to profound deafness. Nine severe to profound hearing-impaired children out of the primer 42 cases, who were detected below two years old, had been selected in the previous study to receive aural habilitation. The average of their speech intelligibility scores was near 70% at age 6, which was accounted as poor oral communication and only two of them were able to communicate by spoken language. An integrated intervention services continued again for one year and their oral communication skill was assessed by their speech intelligibility. The intelligibility test of children was recorded on audio-tape, when they read 10 questions such as where is your home. This can be answered only in one word. Each tape was presented to10 normal hearing listeners, and their task was to write down, the answers in Persian orthography. At the beginning (at age 6 the average speech intelligibility score of these children was 72% and only two of them had score of 90% and 100%. At age 7, all of the severe groups were over 90%, and only two profound ones achieved the score of 48% and 62%. All of severe groups develop oral communication, but profound ones had a semi-intelligible speech

  7. Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine.

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    Lemmens Hendrikus JM

    2010-09-01

    Full Text Available Abstract Background Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia. Methods Patients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events. Results Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36. Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes compared with neostigmine (66.2 minutes; p Conclusions Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694.

  8. Speech timing and working memory in profoundly deaf children after cochlear implantation

    OpenAIRE

    Burkholder, Rose A.; Pisoni, David B.

    2003-01-01

    Thirty-seven profoundly deaf children between 8- and 9-years-old with cochlear implants and a comparison group of normal-hearing children were studied to measure speaking rates, digit spans, and speech timing during digit span recall. The deaf children displayed longer sentence durations and pauses during recall and shorter digit spans compared to the normal-hearing children. Articulation rates, measured from sentence durations, were strongly correlated with immediate memory span in both norm...

  9. Epidemiology of fractures in people with severe and profound developmental disabilities

    Science.gov (United States)

    Glick, N.R.; Fischer, M.H.; Heisey, D.M.; Leverson, G.E.; Mann, D.C.

    2005-01-01

    Fractures are more prevalent among people with severe and profound developmental disabilities than in the general population. In order to characterize the tendency of these people to fracture, and to identify features that may guide the development of preventive strategies, we analyzed fracture epidemiology in people with severe and profound developmental disabilities who lived in a stable environment. Data from a 23-year longitudinal cohort registry of 1434 people with severe and profound developmental disabilities were analyzed to determine the effects of age, gender, mobility, bone fractured, month of fracture, and fracture history upon fracture rates. Eighty-five percent of all fractures involved the extremities. The overall fracture rate increased as mobility increased. In contrast, femoral shaft fracture risk was substantially higher in the least mobile [relative risk (RR), 10.36; 95% confidence interval (CI), 3.29-32.66] compared with the most mobile group. Although the overall fracture rate was not associated with age, the femoral shaft fractures decreased but hand/foot fractures increased with age. Overall fracture risk declined in August and September (RR, 0.70; 95% CI, 0.55-0.89), being especially prominent for tibial/fibular fractures (RR, 0.31; 95% CI, 0.13-0.70). Gender was not a factor in fracture risk. Two primary fracture mechanisms are apparent: one, largely associated with lack of weight-bearing in people with the least mobility, is exemplified by femoral fractures during non-traumatic events as simple as diapering or transfers; the other, probably due to movement- or fall-related trauma, is exemplified by hand/foot fractures in people who ambulate. The fracture experience of people with severe and profound developmental disabilities is unique and, because it differs qualitatively from postmenopausal osteoporosis, may require population-specific methods for assessing risk, for improving bone integrity, and for reduction of falls and accidents

  10. Like cognitive function, decision making across the life span shows profound age-related changes.

    Science.gov (United States)

    Tymula, Agnieszka; Rosenberg Belmaker, Lior A; Ruderman, Lital; Glimcher, Paul W; Levy, Ifat

    2013-10-15

    It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain.

  11. Static and Dynamic Balance in Congenital Severe to Profound Hearing-Impaired Children

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    Farideh HajiHeydari

    2011-09-01

    Full Text Available Background and Aim: Research conducted since the early 1900s has consistently identified differences between deaf and hearing children on performance of a wide variety of motor tasks, most notably balance. Our study was performed to test static and dynamic balance skills in congenital severe to profound hearing impaired children in comparison with normal age-matched children.Methods: This cross-sectional study was conducted on 30 severe to profound hearing impaired and 40 normal children with age 6 to 10 years old. Bruininks-Oseretsky test of motor proficiency 2, balance subset with 9 parts was used for evaluation of balance skills.Results: Hearing-impaired children showed 16.7 to 100% fail results in 7 parts of the balance subset. In normal children fail result was revealed just in 3 parts of the balance subset from 2.5 to 57.5%, and differences between two groups were significant (p<0.0001. There was a significant difference between two groups in two static balance skills of standing on one leg on a line and standing on one leg on a balance beam with eyes closed (p<0.0001.conclusion: It seems that development of static balance skills are longer than dynamic ones. Because severe to profound hearing-impaired children showed more weakness than normal children in both static and dynamic balance abilities, functional tests of balance proficiency can help to identify balance disorders in these children.

  12. Identification of Bioactive Agents and Immunomodulatory Factors from Seashells of the Persian Gulf

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    Arezoo Najafi

    2010-09-01

    Full Text Available Background: Research in marine pharmacology will promise new bioactive agents. The marine bioenvironment is the unique resource for bioactive agents that could not be found in terrestrial organisms. Methods: A total of known 611 seashells species in the Persian Gulf were investigated for synonymy in OBIS database. Then, all the species, including their synonymy were searched in PubMed database to find their isolated bioactive agents. Results: From 611 known seashells in the Persian Gulf, 172 genera/species had bioactive compounds. Bioactive agents were isolated and purified for 16 genera/ species. The crude or purified extracts from these seashells had immunomodulatory effects (6 seashells, anti-toxicologic effects (4 seashells, analgesic (1 seashell, cardiotonic and vasoactive agents (2 seashells, hypolipidemic agents (4 seashells, anti-osteoporotic and osteoblastic agents (2 seashells and anti-dermatitis effect (1 seashell. Conclusion: The known seashells from the Persian Gulf have bioactive and immunomodulatory compounds and increase in the efforts to isolate these agents will promise a treasure for novel anti-infective agents.

  13. Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis

    Science.gov (United States)

    Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; de Morales, José M. García Ruiz; Herreras, Jose M.; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

    2017-01-01

    Abstract Background: To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Methods: Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). Results: We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Conclusions: Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients. PMID:29049193

  14. Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis: A systematic literature review.

    Science.gov (United States)

    Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; Morales, José M García Ruiz de; Herreras, Jose M; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

    2017-10-01

    To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.

  15. In vivo immunomodulatory effects of the methanolic leaf extract of Gymnema sylvestre in Swiss albino mice

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    Ahirwal Laxmi

    2015-01-01

    Full Text Available In the present study we performed a comparative phytochemical analysis of the immunomodulating activities of the methanol leaf extract of Gymnema sylvestre (MLEGS in Swiss albino mice. The phytochemical screening conducted on MLEGS revealed the presence of several phytoconstituents, including saponins, alkaloids, glycosides, phenols, tannins, and flavonoids. Immunomodulatory activities were determined by hemagglutination antibody (HA titer and delayed-type hypersensitivity (DTH tests for determining specific and non-specific immune responses. Flow cytometric techniques were performed for the estimation of B lymphocytes (CD3 and CD19 and Th2 cytokines (IL-2, IFN-γ and IL-4. The response produced by oral administration of MLEGS elicited a significant reduction in a dose-related manner in the primary and secondary antibody response and DTH response. The response produced by oral administration of MLEGS elicited significant reduction in a dose-related manner in the primary and secondary antibody and DTH responses, with maximum reduction observed at 200 mg/kg-body wt. The maximal reductions in the production of CD3, CD19, IL-2, IFN-γ and IL-4 were 31.59, 32.12, 29.51, 32.45 and 33.53%, respectively, at 200 mg/kg body weight. This study demonstrates that G. sylvestre exerts immunosuppressive effects on the components of the immune system of mice, and points to its significant immunomodulatory potential.

  16. Identification and Characterization of Novel Immunomodulatory Bursal-derived Pentapeptide-II (BPP-II)*

    Science.gov (United States)

    Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

    2012-01-01

    The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement. PMID:22184121

  17. Identification and characterization of novel immunomodulatory bursal-derived pentapeptide-II (BPP-II).

    Science.gov (United States)

    Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

    2012-02-03

    The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement.

  18. Nivolumab, a new immunomodulatory drug, a new adverse effect; adrenal crisis

    Directory of Open Access Journals (Sweden)

    Funda Karbek Akarca

    2017-12-01

    Full Text Available Owing to the advancements in medicine, new information is obtained regarding cancer, new antineoplastic agents are developed. Frequent use of these new pharmacological agents emergency physicians to be vigilant about their side effects. We present a case of adrenal crisis in a patient with non-small cell lung cancer (NSCLC, caused by an immunomodulatory drug; nivolumab. While adverse events are related to other immunomodulatory drugs have been reported in literature, our case is the first nivolumab-related adrenal failure to be reported. A patient with lung cancer presented to the emergency room(ER with nausea and vomiting. Hyponatremia, hyperkalemia, persistent hypoglycemia led to the diagnosis of adrenal crisis. Having direct effect on the immune system, these drugs were claimed to be highly reliable. However, there is no reliable data on the side effect profile of these agents. It should be kept in mind that life-threatening auto-immune reactions may occur. Keywords: Nivolumab, Immunomodulation, CTLA 4 antigen, Adrenal crisis

  19. [N-methyl-D-aspartate receptor antibody encephalitis: value of immunomodulatory therapy].

    Science.gov (United States)

    Le Moigno, L; Ternant, D; Paintaud, G; Thibault, G; Cloarec, S; Tardieu, M; Lagrue, E; Castelnau, P

    2014-06-01

    Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is little known to pediatricians and likely underdiagnosed. The child's vital and cognitive prognosis is at stake. The use of immunomodulatory drugs, such as rituximab has led to spectacular results, but many questions remain about its mode of action in this type of pathology. We report the case of a 6-year-old girl with no medical history, admitted for status epilepticus preceded by behavior symptoms and sleep disorders. Gradually, the child became bedridden, mute, and animated by predominantly orofacial dyskinesia. Examinations were normal (cerebrospinal fluid [CSF] analysis, brain MRI). The diagnosis was established by the presence of NMDA-R antibodies in the CSF. After exclusion of a tumor-associated syndrome, treatment was started initially by intravenous immunoglobulins, then by plasma exchange, and finally rituximab. The patient was cured with rituximab despite an unusually early recovery of the B-cell pool. Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a severe but potentially reversible neurologic disorder only recently described, even in childhood. It may be reversible without sequelae if diagnosed and treated early. The use of immunomodulatory therapy, such as rituximab seemingly improves the outcome. Immunological monitoring is needed to better understand its mechanism of action in autoimmune diseases of the nervous system in childhood. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. Antioxidant, immunomodulatory and antiproliferative effects of gelatin hydrolysate from unicorn leatherjacket skin.

    Science.gov (United States)

    Karnjanapratum, Supatra; O'Callaghan, Yvonne C; Benjakul, Soottawat; O'Brien, Nora

    2016-07-01

    The in vitro cellular bioactivities including, antioxidant, immunomodulatory and antiproliferative effects of a gelatin hydrolysate (GH) prepared from unicorn leatherjacket skin, using partially purified glycyl endopeptidase, were investigated in order to optimize the use of fish skin waste products as functional food ingredients. GH under the tested concentrations (750-1500 µg mL(-1) ) protected against H2 O2 -induced DNA damage in U937 cells. GH also protected against the H2 O2 -induced reduction in cellular antioxidant enzyme activities, superoxide dismutase and catalase, in HepG2 cells. GH demonstrated immunomodulatory potential by reducing pro-inflammatory cytokine (interleukin-6 (IL-6) and IL-1β) production and nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Cell proliferation in human colon cancer (Caco-2) cells was significantly reduced in a dose-dependent manner following incubation with GH. These results indicate that GH has several bioactivities which support its potential as a promising functional food ingredient with various health benefits. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  1. Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa

    Science.gov (United States)

    Yue, Grace G. L.; Chan, Ben C. L.; Hon, Po-Ming; Lee, Mavis Y. H.; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara B. S.

    2010-01-01

    The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (3 curcuminoids and 2 turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0–41.8 μg/ml. Alpha-turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of ar-turmerone were shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent. PMID:20438793

  2. Analysis of antimicrobial and immunomodulatory substances produced by heterofermentative Lactobacillus reuteri.

    Science.gov (United States)

    Greifová, Gabriela; Májeková, Hyacinta; Greif, Gabriel; Body, Patrik; Greifová, Maria; Dubničková, Martina

    2017-11-01

    Antimicrobial and immunomodulatory potential of various Lactobacillus reuteri strains is closely connected to their metabolite production profile under given cultivation conditions. We determined the in vitro production of antimicrobial substances such as organic acids, ethanol, and reuterin by four strains of L. reuteri (L. reuteri E, L. reuteri KO5, L. reuteri CCM 3625, and L. reuteri ATCC 55730). All studied L. reuteri strains showed the ability to produce lactic acid, acetic acid, and ethanol with concominant consumption of glucose and together with phenyllactic acid-a potent antifungal compound-with concominant consumption of phenylalanine. The reuterin production from glycerol was confirmed for all analyzed lactobacilli strains except L. reuteri CCM 3625. Production of organic acids, ethanol, and reuterin is significantly involved in antimicrobial activity of lactobacilli which was determined using the dual-culture overlay diffusion method against six indicator bacteria and five indicator moulds. In comparison to the referential L. reuteri ATCC 55730, the highest inhibition potential was observed against Escherichia coli CCM 3988 and Pseudomonas aeruginosa CCM 3955. Among analyzed indicators of moulds, the growth of Alternaria alternata CCM F-128 was the most inhibited by all four analyzed L. reuteri strains. Finally, the immunomodulatory potential of analyzed lactobacilli were proven by the determination of the in vitro production of biogenic amines histamine and tyramine. L. reuteri CCM 3625 was able to produce tyramine, and L. reuteri E and L. reuteri KO5 were able to produce histamine under given cultivation conditions.

  3. Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides

    Science.gov (United States)

    van Dijk, Albert; van Eldik, Mandy; Veldhuizen, Edwin J. A.; Tjeerdsma-van Bokhoven, Hanne L. M.; de Zoete, Marcel R.; Bikker, Floris J.; Haagsman, Henk P.

    2016-01-01

    Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2)-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11) we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1β. In addition, CATH-2 efficiently inhibited IL-1β and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS). N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti-infectives. PMID:26848845

  4. Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides.

    Directory of Open Access Journals (Sweden)

    Albert van Dijk

    Full Text Available Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11 we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1β. In addition, CATH-2 efficiently inhibited IL-1β and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS. N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti-infectives.

  5. Immunomodulatory Activities of a Fungal Protein Extracted from Hericium erinaceus through Regulating the Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Chen Diling

    2017-06-01

    Full Text Available A single-band protein (HEP3 was isolated from Hericium erinaceus using a chemical separation combined with pharmacodynamic evaluation methods. This protein exhibited immunomodulatory activity in lipopolysaccharide-activated RAW 264.7 macrophages by decreasing the overproduction of tumor necrosis factor-α, interleukin (IL-1β, and IL-6, and downregulating the expression of inducible nitric oxide synthase and nuclear factor-κB p65. Further researches revealed that HEP3 could improve the immune system via regulating the composition and metabolism of gut microbiota to activate the proliferation and differentiation of T cells, stimulate the intestinal antigen-presenting cells in high-dose cyclophosphamide-induced immunotoxicity in mice, and play a prebiotic role in the case of excessive antibiotics in inflammatory bowel disease model mice. Aided experiments also showed that HEP3 could be used as an antitumor immune inhibitor in tumor-burdened mice. The results of the present study suggested that fungal protein from H. erinaceus could be used as a drug or functional food ingredient for immunotherapy because of its immunomodulatory activities.

  6. Immunomodulatory Activities of a Fungal Protein Extracted from Hericium erinaceus through Regulating the Gut Microbiota.

    Science.gov (United States)

    Diling, Chen; Chaoqun, Zheng; Jian, Yang; Jian, Li; Jiyan, Su; Yizhen, Xie; Guoxiao, Lai

    2017-01-01

    A single-band protein (HEP3) was isolated from Hericium erinaceus using a chemical separation combined with pharmacodynamic evaluation methods. This protein exhibited immunomodulatory activity in lipopolysaccharide-activated RAW 264.7 macrophages by decreasing the overproduction of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, and downregulating the expression of inducible nitric oxide synthase and nuclear factor-κB p65. Further researches revealed that HEP3 could improve the immune system via regulating the composition and metabolism of gut microbiota to activate the proliferation and differentiation of T cells, stimulate the intestinal antigen-presenting cells in high-dose cyclophosphamide-induced immunotoxicity in mice, and play a prebiotic role in the case of excessive antibiotics in inflammatory bowel disease model mice. Aided experiments also showed that HEP3 could be used as an antitumor immune inhibitor in tumor-burdened mice. The results of the present study suggested that fungal protein from H. erinaceus could be used as a drug or functional food ingredient for immunotherapy because of its immunomodulatory activities.

  7. Evaluation of immunomodulatory effects of lamotrigine in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Abu-Rish Eman Y.

    2017-12-01

    Full Text Available Modulation of the immune system has recently been shown to be involved in the pharmacological effects of old antiepileptic drugs and in the pathogenesis of epilepsy. Therefore, the most recent guidelines for immunotoxicological evaluation of drugs were consulted to investigate the immunomodulatory effects of lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in vivo effects of lamotrigine on delayed-type hypersensitivity (DTH response to sheep red blood cell (SRBC antigens, hemagglutination titer assays and hematological changes. In vitro effects of lamotrigine on ConA-induced splenocyte proliferation and cytokine secretion were assessed. The results showed that lamotrigine treatment significantly increased the DTH response to SRBC in the mouse model of this study. This was accompanied by a significant increase in relative monocyte and neutrophil counts and in spleen cellularity. Lamotrigine significantly inhibited ConA-induced splenocyte proliferation in vitro and it significantly inhibited IL-2 and TNF-α secretion in ConA-stimulated splenocytes. In conclusion, the results demonstrated significant immunomodulatory effects of lamotrigine in BALB/c mice. These data could expand the understanding of lamotrigine-induced adverse reactions and its role in modulating the immune system in epilepsy.

  8. Immunomodulatory effects of balneotherapy with hae-un-dae thermal water on imiquimod-induced psoriasis-like murine model.

    Science.gov (United States)

    Lee, Young Bok; Lee, Jun Young; Lee, Hye Jin; Yun, Seong Taek; Lee, Jong Tae; Kim, Hong Jig; Yu, Dong Soo; Woo, So Youn; Kim, Jin-Wou

    2014-04-01

    Balneotherapy, although not a well-established dermatological treatment, is thought to have therapeutic properties for psoriasis and is used as an alternative treatment modality throughout the world. To evaluate the mechanism underlying the therapeutic immunologic effects of thermomineral water. A murine model of imiquimod-induced psoriasis-like skin inflammation was used for evaluating the therapeutic effects of balneotherapy with Hae-Un-Dae hot spring mineral water. The clinical improvements were evaluated by a dermatologist. Lesional cytokines, including interleukin (IL)-17A, IL-23, and IL-22, were quantitatively measured by real-time reverse transcriptase polymerase chain reaction. Serum levels of interferon-γ, IL-4, IL-5, and IL-17A were measured by enzyme-linked immunosorbent assay. T cell proportions in the spleen were evaluated by flow cytometry, and histopathological evaluation of the skin was also performed. The mineral water balneotherapy group showed faster improvement in skin erythema and scales than the distilled water bathing group. A substantial reduction was observed in the lesional mRNA levels of IL-17A and IL-23 in the mineral water group. Serum levels of IL-4 and IL-5 were significantly decreased in the mineral water group but not in the distilled water group. Normalized T cell proportions were observed after bathing. Balneotherapy showed immunomodulatory effects in a psoriasis-like murine model. Balneotherapy suppressed lesional IL-23 and IL-17A, which are important cytokines in the pathogenesis of psoriasis. These results suggest that balneotherapy can be used as an effective and safe treatment for psoriasis.

  9. Antimicrobial and immunomodulatory efficacy of extracellularly synthesized silver and gold nanoparticles by a novel phosphate solubilizing fungus Bipolaris tetramera.

    Science.gov (United States)

    Fatima, Faria; Bajpai, Preeti; Pathak, Neelam; Singh, Sarika; Priya, Shivam; Verma, Smita Rastogi

    2015-02-27

    Particulates of nanometers size have occupied a significant area in the field of medicinal and agricultural purposes due to their large surface-to-volume ratio and exceptional physicochemical, electronic and mechanical properties. Myconanotechnology, an interface between mycology and nanotechnology is budding nowadays for nanoparticle-fabrication using fungus or its metabolites. In the present study, we have isolated and characterized a novel phosphate solubilizing fungus B. tetramera KF934408 from rhizospheric soil. This phosphatase releasing fungus was subjected to extracellular synthesis of metal nanoparticles by redox reaction. Silver (AgNPs) and gold nanoparticles (AuNPs) were characterized by dynamic light scattering and transmission electron microscopic analysis. The formulated AgNPs were irregular shaped with a size ranging between 54.78 nm to 73.49 nm whereas AuNPs were spherical or hexagonal, with a size of 58.4 and 261.73 nm, respectively. The nanoparticles were assessed for their antibacterial and antifungal efficacy. The results showed effective antimicrobial activity of AgNPs against Bacillus cereus, Staphylococcus aureus, Enterobacter aeroginosa and Trichoderma sp. at higher concentrations, however, AuNPs possessed only moderate antibacterial efficacy while they found no antifungal activity. Cytotoxicity analysis of nanoparticles on J774 and THP1 α cell lines revealed the dose dependence in case of AgNPs, while AuNPs were non-toxic at both low and high doses. Furthermore, significant elevation of intracellular ROS was observed after 4 h of incubation with both the nanoparticles. The capping of fungal proteins on the particulates might be involved in the activities demonstrated by these inert metal nanoparticles. In conclusion, the findings showed that the metal nanoparticles synthesized by fungus B. tetramera could be used as an antimicrobial agents as well as cost effective and nontoxic immunomodulatory delivery vehicle.

  10. Evaluation of immunomodulatory and anti-inflammatory effects and phytochemical screening of Alternanthera tenella Colla (Amaranthaceae aqueous extracts

    Directory of Open Access Journals (Sweden)

    Carla de Agostino Biella

    2008-09-01

    Full Text Available Alternanthera tenella Colla extracts are used in Brazilian traditional folk medicine to treat a variety of infectious diseases as well as inflammation and fever. In this work, the immunomodulatory, anti-inflammatory and potential toxic effects of cold (CAE and hot (HAE aqueous extracts of A. tenella were investigated in vivo. In addition, we analyzed the phytochemical properties of both extracts. BALB/c mice were immunized in vivo with sheep red blood cells and concomitantly inoculated intraperitoneally (i.p. with each extract (50, 100 or 200 mg/kg. Specific antibody-producing cells were enumerated using plaque-forming cell assays (PFC and anti-SRBC IgG and IgM serum levels were measured via enzyme-linked immunosorbent assay. Body and lymphoid organ weights were determined after treatments in order to evaluate toxic effects. Carrageenan-induced paw edema was employed to investigate anti-inflammatory activity in mice inoculated i.p. with CAE or HAE (200 or 400 mg/kg. Phytochemical screening was performed using spectrometric and chromatographic approaches and revealed that CAE possessed higher tannin and flavonoid levels than HAE. PFC numbers were increased after treatment with CAE (100 mg/kg four days after immunization, as were the serum antibody titers after four and seven days, suggesting immunostimulatory activity through modulation of B lymphocyte functions. Body and organ weights did not show major changes, suggesting that extracts administered to mice did not induce significant toxicity. Both extracts had significant anti-inflammatory activity in the paw edema assay. These results suggested that aqueous extracts from A. tenella contained several chemical compounds that possess positive and/or negative modulator effects on the immune system, which appeared to correlate with tannin and flavonoid levels in those extracts. In summary, these studies provide important insight into the biological activities of A. tenella.

  11. Immunomodulatory effects of intravenous bis-1 f(ab')(2) administration in renal-cell cancer-patients

    NARCIS (Netherlands)

    Janssen, R. A. J.; Kroesen, B. J.; Mesander, G.; Sleijfer, D. T.; The, T. Hauw; Mulder, N. H.; de Leij, L

    We report the immunomodulatory effects of an intravenous treatment with F(ab')(2) fragments of the bispecific monoclonal antibody BIS-1 during subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cell cancer (RCC) patients. BIS-1 is directed against both the CD3 antigen on T cells and the

  12. Immunomodulatory Effects of Kuseonwangdogo-Based Mixed Herbal Formula Extracts on a Cyclophosphamide-Induced Immunosuppression Mouse Model

    Directory of Open Access Journals (Sweden)

    Joo Wan Kim

    2018-01-01

    Full Text Available Aim. Kuseonwangdogo is a traditional Korean immunomodulatory polyherbal prescription. However, there are no systemic findings on its complex immunomodulatory effects on in vivo models. In this study, we observed the immunomodulatory effects of Kuseonwangdogo-based mixed herbal formula aqueous extracts (MHFe on cyclophosphamide- (CPA- induced immunosuppression mouse model. Methods. In total, 60 male 6-week-old ICR mice (10 mice/group were selected based on body weight 24 h after the second CPA treatment and used in this experiment. Twelve hours after the end of the last (fourth oral administration of MHFe, the animals were sacrificed. Results. Following CPA treatment, a noticeable decrease in the body, thymus, spleen, and submandibular lymph node (LN weights; white blood cell, red blood cell, platelet number, hemoglobin, and hematocrit concentrations; serum interferon-γ levels; splenic tumor necrosis factor-α, interleukin- (IL- 1β, and IL-10 content; and peritoneal and splenic natural killer cell activities was observed. Depletion of lymphoid cells in the thymic cortex, splenic white pulp, and submandibular LN-related atrophic changes were also observed. However, these CPA-induced myelosuppressive signs were markedly and dose-dependently inhibited by the oral administration of 125, 250, and 500 mg/kg MHFe. Conclusion. MHFe can be a promising, potent immunomodulatory therapeutic agent for various immune disorders.

  13. Comparison of Immunomodulatory Effects of Fresh Garlic and Black Garlic Polysaccharides on RAW 264.7 Macrophages.

    Science.gov (United States)

    Li, Min; Yan, Yi-Xi; Yu, Qing-Tao; Deng, Yong; Wu, Ding-Tao; Wang, Ying; Ge, Ya-Zhong; Li, Shao-Ping; Zhao, Jing

    2017-03-01

    Garlic has a long history to be used for medicine and food purposes. Black garlic, the fermented product of fresh garlic, is considered with better biological activities, such as antioxidant activity, and is developed as an increasingly popular functional food. Polysaccharides are the major components of fresh and black garlic, and immunomodulatory activity is one major pharmacological effect of polysaccharides. Therefore, chemical characteristics and immunomodulatory effects of polysaccharides from fresh and black garlic are investigated and compared in vitro for the 1st time, in order to reveal their molecular and pharmacological differences. It is demonstrated that the molecular weights of polysaccharides from the 2 sources and molar ratios of monosaccharides after acid hydrolysis are greatly variant. The effects of polysaccharides from 2 sources on RAW 264.7 macrophages functions, including promotion of phagocytosis, release of NO, and expressions of several immune-related cytokines (including interleukin [IL]-6, IL-10, tumor necrosis factor alpha, and interferon gamma), were different from each other. The results indicated that fresh garlic polysaccharide exhibited stronger immunomodulatory activities than that of black garlic. Moreover, it is revealed that fructan might be the bioactive component in garlic and it is indicated that during the fermentation treatment, fructan constituents of garlic has degraded, and basically no immunomodulatory effect can be found in black garlic polysaccharides. © 2017 Institute of Food Technologists®.

  14. Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity

    NARCIS (Netherlands)

    Eichner, Ruth; Heider, Michael; Fernández-Sáiz, Vanesa; van Bebber, Frauke; Garz, Anne-Kathrin; Lemeer, Simone|info:eu-repo/dai/nl/311474683; Rudelius, Martina; Targosz, Bianca-Sabrina; Jacobs, Laura; Knorn, Anna-Maria; Slawska, Jolanta; Platzbecker, Uwe; Germing, Ulrich; Langer, Christian; Knop, Stefan; Einsele, Herrmann; Peschel, Christian; Haass, Christian; Keller, Ulrich; Schmid, Bettina; Götze, Katharina S; Kuster, Bernhard; Bassermann, Florian

    Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin

  15. In vivo screening of five phytochemicals/extracts and a fungal immunomodulatory protein against colibacillosis in broilers

    NARCIS (Netherlands)

    Peek, H.W.; Halkes, S.B.A.; Tomassen, M.M.M.; Mes, J.J.; Landman, W.J.M.

    2013-01-01

    Five phytochemicals/extracts (an extract from Echinacea purpurea, a ß-glucan-rich extract from Shiitake, betaine [Betain™], curcumin from Curcuma longa [turmeric] powder, carvacrol and also a recombinant fungal immunomodulatory protein [FIP] from Ganoderma lucidum) cloned and expressed in

  16. Maturation of the mitochondrial redox response to profound asphyxia in fetal sheep.

    Directory of Open Access Journals (Sweden)

    Paul P Drury

    Full Text Available Fetal susceptibility to hypoxic brain injury increases over the last third of gestation. This study examined the hypothesis that this is associated with impaired mitochondrial adaptation, as measured by more rapid oxidation of cytochrome oxidase (CytOx during profound asphyxia.Chronically instrumented fetal sheep at 0.6, 0.7, and 0.85 gestation were subjected to either 30 min (0.6 gestational age (ga, n = 6, 25 min (0.7 ga, n = 27 or 15 min (0.85 ga, n = 17 of complete umbilical cord occlusion. Fetal EEG, cerebral impedance (to measure brain swelling and near-infrared spectroscopy-derived intra-cerebral oxygenation (ΔHb = HbO(2 - Hb, total hemoglobin (THb and CytOx redox state were monitored continuously. Occlusion was associated with profound, rapid fall in ΔHb in all groups to a plateau from 6 min, greatest at 0.85 ga compared to 0.6 and 0.7 ga (p<0.05. THb initially increased at all ages, with the greatest rise at 0.85 ga (p<0.05, followed by a progressive fall from 7 min in all groups. CytOx initially increased in all groups with the greatest rise at 0.85 ga (p<0.05, followed by a further, delayed increase in preterm fetuses, but a striking fall in the 0.85 group after 6 min of occlusion. Cerebral impedance (a measure of cytotoxic edema increased earlier and more rapidly with greater gestation. In conclusion, the more rapid rise in CytOx and cortical impedance during profound asphyxia with greater maturation is consistent with increasing dependence on oxidative metabolism leading to earlier onset of neural energy failure before the onset of systemic hypotension.

  17. The Differential Effects of Attentional Focus in Children with Moderate and Profound Visual Impairments

    Directory of Open Access Journals (Sweden)

    Scott W. T. McNamara

    2017-10-01

    Full Text Available It has been consistently reported that an external focus of attention leads to better motor performance than an internal focus, but no research to date has explored this effect in a population with visual impairments (VI. External focus statements typically reference something in the environment (e.g., target that may be difficult to conceptualize for people with VI since they cannot generate a visual representation of the object of focus. Internal focus statements could be more closely identifiable with proprioception that is not impaired in this population. Recent studies have reported that sighted adults with temporarily obstructed vision are able to receive an external focus benefit when performing discrete tasks (i.e., golf putt and vertical jump, however, it is unclear if those with VI would experience the same benefit. The purpose of this investigation was to compare how an internal focus and external focus impact the balance of children with VI. Eighteen children with VI were grouped into a moderate (n = 11 and a profound VI group (n = 7. Participants completed a familiarization trial, an internal focus trial (i.e., focusing on feet and an external focus trial (i.e., focusing on markers in a counterbalanced order. The moderate VI group had a lower root mean square error while using an external focus (p = 0.04, while the profound VI group did not differ between conditions (p > 0.05. These results suggest that while performing a task reliant on sensory feedback, an external focus benefit may be dependent on the severity of VI. Further research is needed to examine whether external focus statements can be presented in a way that may be more intuitive to those with profound VI. These findings may help to influence how professionals in health-related fields (e.g., physical therapist and physical educators give instructions on motor performance to populations with VI.

  18. Property.

    Science.gov (United States)

    Piele, Philip K.

    Numerous cases in this year's chapter dealt with the same topics of previous years--contracts and bids for building construction, and detachment and annexation of a portion of a school district. The courts continued to attribute board discretionary authority to school boards in school property matters. Intergovernmental disputes over ownership or…

  19. Correlation between audiovestibular function tests and hearing outcomes in severe to profound sudden sensorineural hearing loss.

    Science.gov (United States)

    Wang, Chi-Te; Huang, Tsung-Wei; Kuo, Shih-Wei; Cheng, Po-Wen

    2009-02-01

    This study investigated whether audiovestibular function tests, namely auditory brain stem response (ABR) and vestibular-evoked myogenic potential (VEMP) tests were correlated to hearing outcomes after controlling the effects of other potential confounding factors in severe to profound sudden sensorineural hearing loss (SSHL). Eighty-eight patients with severe to profound SSHL were enrolled in this study. Pretreatment hearing levels, results of audiovestibular function tests, and final hearing outcomes were recorded from retrospective chart reviews. Other factors, including age, gender, delay of treatment, vertigo, diabetes mellitus, and hypertension, were collected as well. Comparative analysis between multiple variables and hearing outcomes was conducted using the cumulative logits model in overall subjects. Further, multivariate analysis of prognostic factors was conducted in the stratified groups of severe (70 dB HL 90 dB HL) SSHL. Multivariate analysis showed that pretreatment hearing levels, presence of vertigo, and results of ABR and VEMP testing were significant outcome predictors in the overall subjects. Stratification analysis demonstrated that both the presence of ABR and VEMP waveforms were significantly correlated with better hearing outcomes in the group of severe SSHL [ABR: adjusted odds ratio (aOR) = 14.7, 95% confidence interval (CI) = 1.78 to 122, p = 0.01; VEMP: aOR = 5.91, 95% CI = 1.18 to 29.5, p = 0.03], whereas the presence of vertigo was the only significant negative prognostic factor in the group of profound SSHL (aOR = 0.24, 95% CI = 0.06 to 0.95, p = 0.04). Other variables, including age, gender, diabetes mellitus, hypertension, and delay of treatment, were not significantly related to hearing outcomes in both groups (p > 0.05). A predictive hearing recovery table with the combined ABR and VEMP results was proposed for the group of severe SSHL. ABR and VEMP tests should be included in the battery of neurootological examinations in

  20. Spider Silk Violin Strings with a Unique Packing Structure Generate a Soft and Profound Timbre

    Science.gov (United States)

    Osaki, Shigeyoshi

    2012-04-01

    We overcome the difficulties in pulling long draglines from spiders, twist bundles of dragline filaments, and succeed in preparing violin strings. The twisting is found to change the cross section shapes of filaments from circular to polygonal and to optimize the packing structure with no openings among filaments providing mechanically strong and elastic strings. The spider string signal peaks of overtones for the violin are relatively large at high frequencies, generating a soft and profound timbre. Such a preferable timbre is considered to be due to the unique polygonal packing structure which provides valuable knowledge for developing new types of materials.

  1. Experience with cochlear implants in Greenlanders with profound hearing loss living in Greenland

    DEFF Research Database (Denmark)

    Homøe, Preben; Andersen, Ture; Grøntved, Aksel

    2013-01-01

    OBJECTIVE: Cochlear implant (CI) treatment was introduced to the world in the 1980s and has become a routine treatment for congenital or acquired severe-to-profound hearing loss. CI treatment requires access to a highly skilled team of ear, nose and throat specialists, audiologists and speech...... years are in need of a CI every second year in Greenland often due to sequelae from meningitis, which may cause postinfectious deafness. Screening of new-borns for hearing has been started in Greenland establishing the basis for early diagnosis of congenital hearing impairment and subsequent...

  2. Profound vision loss impairs psychological well-being in young and middle-aged individuals.

    Science.gov (United States)

    Garcia, Giancarlo A; Khoshnevis, Matin; Gale, Jesse; Frousiakis, Starleen E; Hwang, Tiffany J; Poincenot, Lissa; Karanjia, Rustum; Baron, David; Sadun, Alfredo A

    2017-01-01

    The aim of this study was to evaluate the effects of profound vision loss on psychological well-being in adolescents, young adults, and middle-aged adults with regard to mood, interpersonal interactions, and career-related goals. In addition, we assessed the significance of the resources that may be used to enhance psychological well-being in cases of profound vision loss, and in particular, examined the utility of low vision aids and the role of the ophthalmologist as a provider of emotional support. A questionnaire was issued to individuals aged 13-65 years with profound vision loss resulting from Leber's hereditary optic neuropathy (LHON). Depression prevalence was evaluated with questions regarding major depressive disorder symptomatology. Participants appraised the effects of vision loss on their interpersonal interactions and career goals by providing an impact rating (IR) on a 21-point psychometric scale from -10 to +10. Social well-being index was defined as the average of interpersonal IR and career IR. Subjects were additionally asked about the use of low vision aids and sources of emotional support. A total of 103 participants (mean age =26.4±11.2 years at LHON diagnosis; mean ± standard deviation) completed the questionnaire. Nearly half (49.5%) met the depression criteria after vision loss. Negative impacts on interpersonal interactions (median IR = -5) and career goals (median IR = -6) were observed; both ratings were worse ( P negative interpersonal IR and career IR. Sixty-eight percent of subjects used electronic vision aids; controlling for age, social well-being index was higher among these individuals than for those who did not use electronic aids ( P =0.03). Over half of the participants (52.4%) asserted that they derived emotional support from their ophthalmologist. Profound vision loss in adolescents, young adults, and middle-aged adults is associated with significant negative psychological and psychosocial effects, which are influenced by

  3. Developmental dysgraphia with profound hearing impairment: intervention by auditory methods enabled by cochlear implant.

    Science.gov (United States)

    Fukushima, Kunihiro; Kawasaki, Akihiro; Nagayasu, Rie; Kunisue, Kazuya; Maeda, Yukihide; Kariya, Shin; Kataoka, Yuko; Nishizaki, Kazunori

    2008-06-01

    Learning disability combined with hearing impairment (LDHI) is a poor prognostic factor for the language development of hearing impaired children after educational intervention. A typical example of a child with LDHI and effective interventions provided by cochlear implants are presented in this report. A case of congenital cytomegaloviral infection that showed dysgraphia as well as profound deafness was reported and an underlying visual processing problem diagnosed in the present case caused the patient's dysgraphia. The dysgraphia could be circumvented by the use of auditory memory fairly established by a cochlear implant.

  4. The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis.

    Science.gov (United States)

    Warrender-Sparkes, Matthew; Spelman, Tim; Izquierdo, Guillermo; Trojano, Maria; Lugaresi, Alessandra; Grand'Maison, François; Havrdova, Eva; Horakova, Dana; Boz, Cavit; Oreja-Guevara, Celia; Alroughani, Raed; Iuliano, Gerardo; Duquette, Pierre; Girard, Marc; Terzi, Murat; Hupperts, Raymond; Grammond, Pierre; Petersen, Thor; Fernandez-Bolaños, Ricardo; Fiol, Marcela; Pucci, Eugenio; Lechner-Scott, Jeannette; Verheul, Freek; Cristiano, Edgardo; Van Pesch, Vincent; Petkovska-Boskova, Tatjana; Moore, Fraser; Kister, Ilya; Bergamaschi, Roberto; Saladino, Maria Laura; Slee, Mark; Barnett, Michael; Amato, Maria Pia; Shaw, Cameron; Shuey, Neil; Young, Carolyn; Gray, Orla; Kappos, Ludwig; Butzkueven, Helmut; Kalincik, Tomas; Jokubaitis, Vilija

    2016-04-01

    We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS). MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence. A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, ptreatment compared with other therapies (ptreatment discontinuation. Following the availability of fingolimod, patients were more likely to discontinue injectable treatments. Those who switched to fingolimod were more likely to do so for convenience. Persistence was improved on fingolimod compared to other medications. © The Author(s), 2015.

  5. Design, Synthesis, and Biological Evaluation of γ-Aminopropyl Silatrane-Acyclovir Hybrids with Immunomodulatory Effects.

    Science.gov (United States)

    Ye, Faqing; Song, Xiaoqin; Liu, Jianmin; Xu, Xuemei; Wang, Yuewu; Hu, Lichuan; Wang, Yi; Liang, Guang; Guo, Ping; Xie, Zixin

    2015-10-01

    Several derivatives of γ-aminopropyl silatrane containing acyclovir in their molecular structure were synthesized and evaluated for their immunomodulatory and antiviral activities. The structures of all these derivatives were confirmed by mass spectra, IR, and (1) H NMR. Based on WST-1 assay in vitro, these compounds could stimulate proliferation of splenic lymphocytes at certain concentrations. Furthermore, compound 3d could also potentiate the expression of IFN-γ, IL-2, CD4(+) , CD8(+) , and CD4(+) /CD8(+) in vivo. Our results show that these derivatives possess antiviral activity against herpes simplex viruses with a similar potency to acyclovir without a cellular immune response. © 2015 John Wiley & Sons A/S.

  6. The Immunomodulatory Effects of Mesenchymal Stem Cell Polarization within the Tumor Microenvironment Niche

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    Cosette M. Rivera-Cruz

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs represent a promising tool for cell therapy, particularly for their antitumor effects. This cell population can be isolated from multiple tissue sources and also display an innate ability to home to areas of inflammation, such as tumors. Upon entry into the tumor microenvironment niche, MSCs promote or inhibit tumor progression by various mechanisms, largely through the release of soluble factors. These factors can be immunomodulatory by activating or inhibiting both the adaptive and innate immune responses. The mechanisms by which MSCs modulate the immune response are not well understood. Because of this, the relationship between MSCs and immune cells within the tumor microenvironment niche continues to be an active area of research in order to help explain the apparent contradictory findings currently available in the literature. The ongoing research aims to enhance the potential of MSCs in future therapeutic applications.

  7. A comparative study on immunomodulatory activity of polysaccharides from two official species of Ganoderma (Lingzhi).

    Science.gov (United States)

    Meng, Lan-Zhen; Xie, Jing; Lv, Guang-Ping; Hu, De-Jun; Zhao, Jing; Duan, Jin-Ao; Li, Shao-Ping

    2014-01-01

    Two Ganoderma species, G. lucidum and G. sinense, are listed as Lingzhi in Chinese Pharmacopoeia and they are considered to have the same therapeutic effects. Polysaccharides were the main immunomodulatory and anticancer components in Ganoderma. In this study, the chemical characters and the effects of polysaccharides from G. lucidum (GLPS) and G. sinense (GSPS) on macrophage functions were investigated and compared. Chemical studies showed that GLPS and GSPS were different, displaying various molecular weight distribution and ratio of monosaccharide components. In vitro pharmacological studies showed that both GLPS and GSPS had potent effects on macrophage functions, such as promoting macrophage phagocytosis, increasing their release of nitric oxide and cytokines interleukin (IL)-1α, IL-6, IL-10, and tumor necrosis factor-α. Generally, GLPS was more powerful than GSPS. This study is helpful to elucidate the active components and pharmacological variation between the 2 Ganoderma species. The structure-activity relationship of polysaccharides from Ganoderma needs further study.

  8. Immunomodulatory effects of Hericium erinaceus derived polysaccharides are mediated by intestinal immunology.

    Science.gov (United States)

    Sheng, Xiaotong; Yan, Jingmin; Meng, Yue; Kang, Yuying; Han, Zhen; Tai, Guihua; Zhou, Yifa; Cheng, Hairong

    2017-03-22

    This study was aimed at investigating the immunomodulating activity of Hericium erinaceus polysaccharide (HEP) in mice, by assessing splenic lymphocyte proliferation (cell-mediated immunity), serum hemolysin levels (humoral immunity), phagocytic capacity of peritoneal cavity phagocytes (macrophage phagocytosis), and NK cell activity. ELISA of immunoglobulin A (SIgA) in the lamina propria, and western blotting of small intestinal proteins were also performed to gain insight into the mechanism by which HEP affects the intestinal immune system. Here, we report that HEP improves immune function by functionally enhancing cell-mediated and humoral immunity, macrophage phagocytosis, and NK cell activity. In addition, HEP was found to upregulate the secretion of SIgA and activate the MAPK and AKT cellular signaling pathways in the intestine. In conclusion, all these results allow us to postulate that the immunomodulatory effects of HEP are most likely attributed to the effective regulation of intestinal mucosal immune activity.

  9. Immunomodulatory effects of hydroxyethylated Hericium erinaceus polysaccharide on macrophages RAW264.7.

    Science.gov (United States)

    Ren, Zhe; Qin, Tao; Qiu, Fuan; Song, Yulong; Lin, Dandan; Ma, Yufang; Li, Jian; Huang, Yifan

    2017-12-01

    Hericium erinaceus polysaccharide (HEP) has been shown to possess a variety of biological activities. In present study, HEP was successfully modified to obtain its hydroxyethylated derivative hHEP. Its potential immunomodulatory activities on RAW264.7 macrophages were investigated. Results showed that the hHEP were significantly stronger than that of the corresponding unmodified polysaccharide, HEP. Meanwhile, the NO, IL-6 and TNF-α production activities of macrophages were enhanced in the RAW264.7 macrophages by stimulation of hHEP. In addition, the hHEP increase significantly higher iNOS expression than HEP. These results indicated that the hydroxyethylated derivative hHEP could enhance the activation of peritoneal macrophages, and hydroxyethylation modification can enhance the immunomodulation function of HEP. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Immunomodulatory activity of dioscorin, the storage protein of yam (Dioscorea alata cv. Tainong No. 1) tuber.

    Science.gov (United States)

    Liu, Yen-Wenn; Shang, Huey-Fang; Wang, Chung-Kwe; Hsu, Feng-Lin; Hou, Wen-Chi

    2007-11-01

    The purified dioscorin from yam (Dioscorea alata L. cv. Tainong 1) tuber was previously reported (Hsu et al., 2002. J. Agric. Food Chem., 50, 6109-6113). In this report, we evaluated its immunomodulatory ability in vitro in the presence of polymyxin B (50 microg/ml) to eliminate lipopolysaccharide (LPS) contamination. Dioscorin (5-100 microg/ml) was able to stimulate nitric oxide production (expressed as nitrite concentrations) in RAW264.7 cells. The stimulation index on the phagocytosis of RAW264.7 cells against E. coli and the oxidative burst (determined by the intensity of rhodamine fluorescence) of RAW264.7 cells were both enhanced by different concentrations of dioscorin (5-100 microg/ml). The cytokine production, including IL-6, TNF-alpha, and IL-1beta in dioscorin-treated RAW264.7 cells or human monocytes, was measured in the cultured medium. Dioscorin (5-100 microg/ml) was found able to induce IL-6, TNF-alpha, and IL-1beta production in RAW264.7 cells and human monocytes. To evaluate the effects of dioscorin on the proliferation of spleen cells from BALB/c mice, phytohemagglutinin (PHA, 2 microg/ml) alone or PHA mixed with different concentrations of dioscorin (10, 25, and 50 microg/ml) was used to treat spleen cells for 24h. The stimulated proliferation index of splenic cells ranged from 1.38- to 1.48-fold of PHA alone for PHA mixed with different concentrations of dioscorin (10, 25, and 50 microg/ml). We suggest that the tuber storage protein of yam dioscorin functions as an immunomodulatory substance.

  11. Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients

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    Wim Adriaensen

    2018-01-01

    Full Text Available Patients with visceral leishmaniasis (VL–human immunodeficiency virus (HIV coinfection experience increased drug toxicity and treatment failure rates compared to VL patients, with more frequent VL relapse and death. In the era of VL elimination strategies, HIV coinfection is progressively becoming a key challenge, because HIV-coinfected patients respond poorly to conventional VL treatment and play an important role in parasite transmission. With limited chemotherapeutic options and a paucity of novel anti-parasitic drugs, new interventions that target host immunity may offer an effective alternative. In this review, we first summarize current views on how VL immunopathology is significantly affected by HIV coinfection. We then review current clinical and promising preclinical immunomodulatory interventions in the field of VL and discuss how these may operate in the context of a concurrent HIV infection. Caveats are formulated as these interventions may unpredictably impact the delicate balance between boosting of beneficial VL-specific responses and deleterious immune activation/hyperinflammation, activation of latent provirus or increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a target molecule and a more detailed account of the immunological status induced by the coinfection as well as surrogate markers of cure and protection are still required. We do, however, argue that virologically suppressed VL patients with a recovered immune system, in whom effective antiretroviral therapy alone is not able to restore protective immunity, can be considered a relevant target group for an immunomodulatory intervention. Finally, we provide perspectives on the translation of novel theories on synergistic immune cell cross-talk into an effective treatment strategy for VL–HIV-coinfected patients.

  12. The Immunomodulatory Effect of Acupoint Application for Childhood Asthma: A Systematic Review and Meta-Analysis

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    Xiao Cun Yang

    2015-01-01

    Full Text Available Objective. To evaluate the evidence on the immunomodulatory effect of acupoint application for childhood asthma. Methods. Five electronic databases through October 2014 were searched. The risk of bias in eligible studies was assessed using the Cochrane Collaboration tool. Standardised mean difference (SMD and 95% confidence intervals (CI of random-effects model were calculated. And heterogeneity was assessed using the Cochran Q statistic and quantified with the I2 index. Results. Six studies were included in our review. The aggregated results suggested that acupoint application showed the beneficial effect for childhood asthma in improving IgA (SMD, −0.83; 95% CI −1.14 to −0.52; P<0.00001, IgE (SMD, −0.52; 95% CI −0.76 to −0.29; P<0.001, IgG (SMD, −1.17; 95% CI −1.61 to −0.74; P<0.0001, IL-4 (SMD, −0.57; 95% CI −0.91 to −0.23; P=0.0009, and IFN-γ (SMD, −0.38; 95% CI −0.71 to −0.04; P=0.03 but not IgM (SMD, −0.40; 95% CI −0.98 to 0.18; P=0.18. And the effective dose of acupoint application may be 2–6 hours/time and a total of 3 times within 4 weeks. Conclusions. This review showed the positive evidence that acupoint application had the favorable immunomodulatory effect for childhood asthma. However, more studies with long follow-up are warrant to confirm the current findings.

  13. Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients

    Science.gov (United States)

    Adriaensen, Wim; Dorlo, Thomas P. C.; Vanham, Guido; Kestens, Luc; Kaye, Paul M.; van Griensven, Johan

    2018-01-01

    Patients with visceral leishmaniasis (VL)–human immunodeficiency virus (HIV) coinfection experience increased drug toxicity and treatment failure rates compared to VL patients, with more frequent VL relapse and death. In the era of VL elimination strategies, HIV coinfection is progressively becoming a key challenge, because HIV-coinfected patients respond poorly to conventional VL treatment and play an important role in parasite transmission. With limited chemotherapeutic options and a paucity of novel anti-parasitic drugs, new interventions that target host immunity may offer an effective alternative. In this review, we first summarize current views on how VL immunopathology is significantly affected by HIV coinfection. We then review current clinical and promising preclinical immunomodulatory interventions in the field of VL and discuss how these may operate in the context of a concurrent HIV infection. Caveats are formulated as these interventions may unpredictably impact the delicate balance between boosting of beneficial VL-specific responses and deleterious immune activation/hyperinflammation, activation of latent provirus or increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a target molecule and a more detailed account of the immunological status induced by the coinfection as well as surrogate markers of cure and protection are still required. We do, however, argue that virologically suppressed VL patients with a recovered immune system, in whom effective antiretroviral therapy alone is not able to restore protective immunity, can be considered a relevant target group for an immunomodulatory intervention. Finally, we provide perspectives on the translation of novel theories on synergistic immune cell cross-talk into an effective treatment strategy for VL–HIV-coinfected patients. PMID:29375567

  14. Immunomodulatory Effectiveness of Aqueous Obat Pahit Extract of Lingga Malay Ethnic on White Rats (Rattus novergicus

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    Fitmawati Fitmawati

    2017-12-01

    Full Text Available Obat pahit has been generally known and believed by Lingga Malay society as anti-aging agent. However, the study of Obat pahit is not scientifically proven. This research was aimed to prove immunomodulatory ability of Obat pahit potion from Lingga, Riau Archipelago. This study used white rats as an animal modelling, and Staphylococcus aureus as bacteria tester. The rats had been treated with aqueous Obat pahit extract from three TMPs on dose scales of 0.09, 0.18 and 0.27 mL/200g of body weight through oral administration for 7 days. Furthermore, on the 8th days, the experiment animals were injected by the preparation of bacteria tester through intraperitoneal administration in the amount of 0.5 mL/200 gram of body weigth and subsequently incubated for 1 hour after the injection. There were 2 observed parameters on this study, i.e efectivity and capacity of phagocytosis by leukocytes. The observation of leukocytes-phagocytocis activity was carried out by making a smear preparat samples of peritoneum fluid from rats. After the observation under microscope on a magnification of 100 times. The result was obtained the Obat pahit from Kalan PMT swere more effective on dose 2, while from SP4 and Linau TMPs were much more effective on dose 1. It is therefore, using these data of the results, the advanced doses scale of this Obat pahit would not be necessary. Obat pahit potion from Malay Lingga Malay Ethnic could become raw materials of immunomodulatory herbal medicine based on traditional knowledge. It also potentially as a standardized herbal.

  15. A Parametric Study on the Immunomodulatory Effects of Electroacupuncture in DNP-KLH Immunized Mice

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    Sun Kwang Kim

    2011-01-01

    Full Text Available This study was conducted to compare the effects of low frequency electroacupuncture (EA and high frequency EA at acupoint ST36 on the production of IgE and Th1/Th2 cytokines in BALB/c mice that had been immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH, as well as to investigate the difference in the immunomodulatory effects exerted by EA stimulations at acupoint ST36 and at a non-acupoint (tail. Female BALB/c mice were divided into seven groups: normal (no treatments, IM (immunization only, ST36-PA (IM + plain acupuncture at ST36, ST36-LEA (IM + low frequency (1 Hz EA at ST36, ST36-HEA (IM + high frequency (120 Hz EA at ST36, NA-LEA (IM + low frequency (1 Hz EA at non-acupoint and NA-HEA (IM + high frequency (120 Hz EA at non-acupoint. EA stimulation was performed daily for two weeks, and total IgE, DNP-KLH specific IgE, IL-4 and IFN-γ levels were measured at the end of the experiment. The results of this study showed that the IgE and IL-4 levels were significantly suppressed in the ST36-LEA and ST36-HEA groups, but not in the NA-LEA and NA-HEA groups. However, there was little difference in the immunomodulatory effects observed in the ST36-LEA and ST36-HEA groups. Taken together, these results suggest that EA stimulation-induced immunomodulation is not frequency dependent, but that it is acupoint specific.

  16. Chemical composition and immunomodulatory effects of enzymatic protein hydrolysates from common carp (Cyprinus carpio) egg.

    Science.gov (United States)

    Chalamaiah, M; Hemalatha, R; Jyothirmayi, T; Diwan, Prakash V; Bhaskarachary, K; Vajreswari, A; Ramesh Kumar, R; Dinesh Kumar, B

    2015-02-01

    The aim of this study was to prepare protein hydrolysates from underutilized common carp (Cyprinus carpio) egg and to investigate their immunomodulatory effects in vivo. Common carp (Cyprinus carpio) egg (roe) was hydrolysed by pepsin, trypsin, and Alcalase. Chemical composition (proximate, amino acid, mineral and fatty acid compositions) and molecular mass distribution of the three hydrolysates were determined. The carp egg protein hydrolysates (CEPHs) were evaluated for their immunomodulatory effects in BALB/c mice. CEPHs (0.25, 0.5 and 1 g/kg body weight) were orally administered daily to female BALB/c mice (4-6 wk, 18-20 g) for a period of 45 d. After 45 d, mice were sacrificed and different tissues were collected for the immunologic investigations. The three hydrolysates contained high protein content (64%-73%) with all essential amino acids, and good proportion of ω-3 fatty acids, especially docosahexaenoic acid. Molecular mass analysis of hydrolysates confirmed the conversion of large-molecular-weight roe proteins into peptides of different sizes (5-90 kDa). The three hydrolysates significantly enhanced the proliferation of spleen lymphocytes. Pepsin hydrolysate (0.5 g/kg body weight) significantly increased the splenic natural killer cell cytotoxicity, mucosal immunity (secretory immunoglobulin A) in the gut and level of serum immunoglobulin A. Whereas Alcalase hydrolysate induced significant increases in the percentages of CD4+ and CD8+ cells in spleen. The results demonstrate that CEPHs are able to improve the immune system and further reveal that different CEPHs may exert differential influences on the immune function. These results indicate that CEPHs could be useful for several applications in the health food, pharmaceutical, and nutraceutical industries. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Immunomodulatory Role of Stem Cell from Human Exfoliated Deciduous Teeth on Periodontal Regeneration.

    Science.gov (United States)

    Gao, Xianling; Shen, Zongshan; Guan, Meiliang; Huang, Qiting; Chen, Lingling; Qin, Wei; Ge, Xiaohu; Chen, Haijia; Xiao, Yin; Lin, Zhengmei

    2018-03-20

    Periodontitis is initiated by the infection of periodontal bacteria and subsequent tissue inflammation due to immunoreaction, eventually leading to periodontal apparatus loss. Stem cells from human exfoliated deciduous teeth (SHEDs) have exhibited beneficial characteristics in dental tissue regeneration. However, the immunomodulatory functions of SHEDs have not been elucidated in the context of periodontitis treatment. In this study, we investigated the potential immunomodulatory effects of SHEDs on experimental periodontitis and demonstrated that multi-dose delivery of SHEDs led to periodontal tissue regeneration. SHEDs and monocytes/macrophages were cocultured in transwell systems and SHEDs were found to be capable of promoting monocyte/macrophages conversion to CD206+ M2-like phenotype. Bioluminescence imaging (BLI) was employed to assess the survival and distribution of SHEDs after delivery in periodontal tissues in an induced periodontitis model, and BLI revealed that SHEDs survived for approximately 7 days in periodontal tissues with little tissue diffusion. Then, multi-dose SHEDs delivery was applied to treat periodontitis at 7-day intervals. Results showed that muti-dose SHEDs altered the cytokine expression profile in gingival crevicular fluid, reduced gum bleeding, increased new attachment of periodontal ligament and decreased osteoclast differentiation. Micro-computed tomography analysis showed SHEDs administration significantly increased periodontal regeneration and alveolar bone volume, and decreased distance of cementoenamel junction to alveolar bone crest (CEJ-ABC). Furthermore, an increase in the number of CD206+ M2 macrophages was observed in periodontal tissues following the delivery of SHEDs, which aligned well with the promoted conversion to CD206+ M2-like cells from monocytes/macrophages in vitro after stimulation by SHEDs. This study demonstrated in a rat periodontitis model that local delivery of SHEDs attributed to the induction of M2

  18. Immunomodulatory activity of Lactobacillus plantarum KLDS1.0318 in cyclophosphamide-treated mice

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    Yueyue Meng

    2018-03-01

    Full Text Available Background: Probiotics in fermented foods have attracted considerable attention lately as treatment options for immune diseases, the incidence of which has been increasing throughout the world. Objective: The objective of the present study was to investigate the immunomodulatory activity of Lactobacillus plantarum (L. plantarum KLDS1.0318 in cyclophosphamide-treated mice. Design: To investigate the immune-enhancing effects of L. plantarum KLDS1.0318, we used a immunosuppressive model. Ninety female six-week-old BALB/c mice were randomly divided into six groups: normal control (NC group, model control (MC group, immunosuppression plus L. plantarum KLDS1.0318 groups with three different doses (KLDS1.0318-L, KLDS1.0318-M, and KLDS1.0318-H, and plus levamisole hydrochloride as positive control (PC group. Results and discussions: Results showed that the thymus and spleen indexes of the four treatment groups were significantly higher than those of the MC group (2.01±0.16 ( p < 0.05. The capacity of lymphocyte proliferation, the activity of natural killer (NK cell and macrophages phagocytosis were significantly increased ( p < 0.05 in four treatment groups as compared with the MC group (0.327±0.022, 62.29±0.8, 0.087±0.008, respectively. The levels of relative immune factors (IL-2, IL-6, and IFN-γ showed similar patterns ( p < 0.05. Conclusions: This study suggested that orally administered L.plantarum KLDS1.0318 may effectively accelerate the recovery of immunosuppressive mice caused by cyclophosphamide (CTX. The immunomodulatory activity of the srtain recommended that L. plantarum KLDS1.0318 could be used as a powerful medicinal treatment against immunosuppression.

  19. Whole exome sequencing identifies mutations in Usher syndrome genes in profoundly deaf Tunisian patients.

    Science.gov (United States)

    Riahi, Zied; Bonnet, Crystel; Zainine, Rim; Lahbib, Saida; Bouyacoub, Yosra; Bechraoui, Rym; Marrakchi, Jihène; Hardelin, Jean-Pierre; Louha, Malek; Largueche, Leila; Ben Yahia, Salim; Kheirallah, Moncef; Elmatri, Leila; Besbes, Ghazi; Abdelhak, Sonia; Petit, Christine

    2015-01-01

    Usher syndrome (USH) is an autosomal recessive disorder characterized by combined deafness-blindness. It accounts for about 50% of all hereditary deafness blindness cases. Three clinical subtypes (USH1, USH2, and USH3) are described, of which USH1 is the most severe form, characterized by congenital profound deafness, constant vestibular dysfunction, and a prepubertal onset of retinitis pigmentosa. We performed whole exome sequencing in four unrelated Tunisian patients affected by apparently isolated, congenital profound deafness, with reportedly normal ocular fundus examination. Four biallelic mutations were identified in two USH1 genes: a splice acceptor site mutation, c.2283-1G>T, and a novel missense mutation, c.5434G>A (p.Glu1812Lys), in MYO7A, and two previously unreported mutations in USH1G, i.e. a frameshift mutation, c.1195_1196delAG (p.Leu399Alafs*24), and a nonsense mutation, c.52A>T (p.Lys18*). Another ophthalmological examination including optical coherence tomography actually showed the presence of retinitis pigmentosa in all the patients. Our findings provide evidence that USH is under-diagnosed in Tunisian deaf patients. Yet, early diagnosis of USH is of utmost importance because these patients should undergo cochlear implant surgery in early childhood, in anticipation of the visual loss.

  20. Profound microcephaly, primordial dwarfism with developmental brain malformations: a new syndrome.

    Science.gov (United States)

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Saleem, Sahar N; Ahmed, Mahmoud K H; Issa, Mahmoud; Effat, Laila K; Kayed, Hisham F; Zaki, Maha S; Gaber, Khaled R

    2012-08-01

    We describe two sibs with a lethal form of profound congenital microcephaly, intrauterine and postnatal growth retardation, subtle skeletal changes, and poorly developed brain. The sibs had striking absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular micro-retrognathia. Brain magnetic resonance imaging (MRI) revealed extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormally shaped hippocampus, and proportionately affected cerebellum and brainstem. In addition, fundus examination showed foveal hypoplasia with optic nerve atrophy. No abnormalities of the internal organs were found. This profound form of microcephaly was identified at 17 weeks gestation by ultrasound and fetal brain MRI helped in characterizing the developmental brain malformations in the second sib. Molecular analysis excluded mutations in potentially related genes such as RNU4ATAC, SLC25A19, and ASPM. These clinical and imaging findings are unlike that of any recognized severe forms of microcephaly which is believed to be a new microcephalic primordial dwarfism (MPD) with developmental brain malformations with most probably autosomal recessive inheritance based on consanguinity and similarly affected male and female sibs. Copyright © 2012 Wiley Periodicals, Inc.

  1. Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy.

    Science.gov (United States)

    Mercimek-Mahmutoglu, Saadet; Horvath, Gabriella A; Coulter-Mackie, Marion; Nelson, Tanya; Waters, Paula J; Sargent, Michael; Struys, Eduard; Jakobs, Cornelis; Stockler-Ipsiroglu, Sylvia; Connolly, Mary B

    2012-05-01

    Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

  2. Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Stivaros, Stavros M. [Manchester Academic Health Science Centre, Academic Unit of Paediatric Radiology, Royal Manchester Children' s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester (United Kingdom); University of Manchester, Centre for Imaging Sciences, Institute of Population Health, Manchester (United Kingdom); Radon, Mark R. [The Walton Centre NHS Foundation Trust, Department of Neuroradiology, Liverpool (United Kingdom); Mileva, Reneta; Gledson, Ann; Keane, John A. [University of Manchester, School of Computer Science, Manchester (United Kingdom); Connolly, Daniel J.A.; Batty, Ruth [Sheffield Children' s Hospital NHS Foundation Trust, Department of Neuroradiology, Sheffield (United Kingdom); Cowell, Patricia E. [University of Sheffield, Department of Human Communication Sciences, Sheffield (United Kingdom); Hoggard, Nigel; Griffiths, Paul D. [University of Sheffield, Academic Unit of Radiology, Sheffield (United Kingdom); Wright, Neville B.; Tang, Vivian [Manchester Academic Health Science Centre, Academic Unit of Paediatric Radiology, Royal Manchester Children' s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester (United Kingdom)

    2016-01-15

    Birth-related acute profound hypoxic-ischaemic brain injury has specific patterns of damage including the paracentral lobules. To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Study subjects included 13 children with proven acute profound hypoxic-ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. There was statistically significant narrowing of the mid-posterior body and genu of the corpus callosum in children with hypoxic-ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Focal volume loss is seen in the corpus callosum of children with hypoxic-ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic-ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic-ischaemic brain injury. (orig.)

  3. Validation of the Spanish version of the Baylor Profound Mental Status Examination.

    Science.gov (United States)

    Salmerón, Sergio; Huedo, Isabel; López-Utiel, Melisa; Soler-Moratalla, Isabel; Flores-Ruano, Teresa; Fernández-Sánchez, Miguel; Noguerón, Alicia; Doody, Rachelle S; Abizanda, Pedro

    2016-01-01

    There are no short valid instruments to evaluate cognitive status in severe Alzheimer's disease (AD) patients in the Spanish language. To validate the Spanish version of the Baylor Profound Mental Status Examination (BPMSE-Sp). The Baylor Profound Mental Status Examination (BPMSE) was translated to Spanish and back translated. Validation was conducted in 100 patients with severe probable AD with a Mini-Mental State Examination (MMSE) reliability. The mean age of patients was 84.9; 74% were female; 64% were institutionalized. The mean MMSE was 5.6; the mean BPMSE-Sp was 13.6; the mean BPMSE-Sp behavior was 1.2; the mean SIB was 42.2; and the mean NPI-Q was 4.7. BPMSE-Sp presented good internal consistency (Cronbach α= 0.84). There were significant correlations between the BPMSE-Sp and MMSE (r = 0.86, p reliability were in both cases excellent, ranging between 0.96 and 0.99 (p <  0.001). BPMSE-Sp had fewer floor and ceiling effects than the MMSE. The BPMSE-Sp is a valid tool for use in daily practice and research in the evaluation of cognitive function of patients with severe AD.

  4. Loss of CIB2 Causes Profound Hearing Loss and Abolishes Mechanoelectrical Transduction in Mice

    Directory of Open Access Journals (Sweden)

    Yanfei Wang

    2017-12-01

    Full Text Available Calcium and integrin-binding protein 2 (CIB2 belongs to a protein family with four known members, CIB1 through CIB4, which are characterized by multiple calcium-binding EF-hand domains. Among the family members, the Cib1 and Cib2 genes are expressed in mouse cochlear hair cells, and mutations in the human CIB2 gene have been associated with nonsyndromic deafness DFNB48 and syndromic deafness USH1J. To further explore the function of CIB1 and CIB2 in hearing, we established Cib1 and Cib2 knockout mice using the clustered regularly interspaced short palindromic repeat (CRISPR-associated Cas9 nuclease (CRISPR/Cas9 genome editing technique. We found that loss of CIB1 protein does not affect auditory function, whereas loss of CIB2 protein causes profound hearing loss in mice. Further investigation revealed that hair cell stereocilia development is affected in Cib2 knockout mice. Noticeably, loss of CIB2 abolishes mechanoelectrical transduction (MET currents in auditory hair cells. In conclusion, we show here that although both CIB1 and CIB2 are readily detected in the cochlea, only loss of CIB2 results in profound hearing loss, and that CIB2 is essential for auditory hair cell MET.

  5. Whole exome sequencing identifies mutations in Usher syndrome genes in profoundly deaf Tunisian patients.

    Directory of Open Access Journals (Sweden)

    Zied Riahi

    Full Text Available Usher syndrome (USH is an autosomal recessive disorder characterized by combined deafness-blindness. It accounts for about 50% of all hereditary deafness blindness cases. Three clinical subtypes (USH1, USH2, and USH3 are described, of which USH1 is the most severe form, characterized by congenital profound deafness, constant vestibular dysfunction, and a prepubertal onset of retinitis pigmentosa. We performed whole exome sequencing in four unrelated Tunisian patients affected by apparently isolated, congenital profound deafness, with reportedly normal ocular fundus examination. Four biallelic mutations were identified in two USH1 genes: a splice acceptor site mutation, c.2283-1G>T, and a novel missense mutation, c.5434G>A (p.Glu1812Lys, in MYO7A, and two previously unreported mutations in USH1G, i.e. a frameshift mutation, c.1195_1196delAG (p.Leu399Alafs*24, and a nonsense mutation, c.52A>T (p.Lys18*. Another ophthalmological examination including optical coherence tomography actually showed the presence of retinitis pigmentosa in all the patients. Our findings provide evidence that USH is under-diagnosed in Tunisian deaf patients. Yet, early diagnosis of USH is of utmost importance because these patients should undergo cochlear implant surgery in early childhood, in anticipation of the visual loss.

  6. Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

    International Nuclear Information System (INIS)

    Stivaros, Stavros M.; Radon, Mark R.; Mileva, Reneta; Gledson, Ann; Keane, John A.; Connolly, Daniel J.A.; Batty, Ruth; Cowell, Patricia E.; Hoggard, Nigel; Griffiths, Paul D.; Wright, Neville B.; Tang, Vivian

    2016-01-01

    Birth-related acute profound hypoxic-ischaemic brain injury has specific patterns of damage including the paracentral lobules. To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Study subjects included 13 children with proven acute profound hypoxic-ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. There was statistically significant narrowing of the mid-posterior body and genu of the corpus callosum in children with hypoxic-ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Focal volume loss is seen in the corpus callosum of children with hypoxic-ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic-ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic-ischaemic brain injury. (orig.)

  7. Developing a questionnaire on physical activity support of people with (profound) intellectual (and multiple) disabilities : Experiences from the Netherlands

    NARCIS (Netherlands)

    Bossink, Leontien; van der Putten, Annette; Vlaskamp, Carla

    2017-01-01

    Introduction: People with intellectual disabilities (ID) undertake extremely low levels of physical activity, which is even more true in people with profound intellectual and multiple disabilities (PIMD). Physical activity approaches, particularly for people with PIMD, are more likely to be

  8. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

    NARCIS (Netherlands)

    Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

    Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were

  9. Examining relationships between staff attributions of soundscapes and core affect in people with severe or profound intellectual and visual disabilities

    NARCIS (Netherlands)

    van den Bosch, Kirsten A.; Vlaskamp, Carla; Andringa, Tjeerd C.; Post, Wendy J.; Ruijssenaars, Wied A.J.J.M.

    Background: People with profound intellectual disabilities experience a high prevalence of visual disabilities, making them more dependent on sound. However, research addressing the influence of the auditory environment is scarce. Method: Observations of the auditory environments (soundscapes) and

  10. An atypical case of successful resuscitation of an accidental profound hypothermia patient, occurring in a temperate climate.

    LENUS (Irish Health Repository)

    Coleman, E

    2010-03-01

    Cases of accidental profound hypothermia occur most frequently in cold, northern climates. We describe an atypical case, occurring in a temperate climate, where a hypothermic cardiac-arrested patient was successfully resuscitated using extracorporeal circulation (ECC).

  11. Informal social networks of people with profound intellectual and multiple disabilities : Relationship with age, communicative abilities and current living arrangements

    NARCIS (Netherlands)

    Kamstra, A.; van der Putten, A.A.J.; Post, W.J.; Vlaskamp, C.

    2015-01-01

    BACKGROUND: People with profound intellectual and multiple disabilities (PIMD) have limited informal social contacts. Research to determine the factors which can positively influence establishing sound informal social contacts is required. MATERIALS AND METHODS: Regression analysis for 200 people

  12. High proportion of PD-1-expressing CD4+ T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence.

    Science.gov (United States)

    Damouche, Abderaouf; Pourcher, Guillaume; Pourcher, Valérie; Benoist, Stéphane; Busson, Elodie; Lataillade, Jean-Jacques; Le Van, Mélanie; Lazure, Thierry; Adam, Julien; Favier, Benoit; Vaslin, Bruno; Müller-Trutwin, Michaela; Lambotte, Olivier; Bourgeois, Christine

    2017-12-01

    We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART-controlled HIV infection was associated with a difference in the CD4/CD8 T-cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue. No changes in Th1, Th2 and Th17 cell proportions or activation markers expression on T cell (Ki-67, HLA-DR) could be detected, and the percentage of CD69-expressing resident memory CD4 + T cells was not affected. Overall, our results indicate that adipose-tissue-resident CD4 + T cells are not extensively activated during HIV infection. PD-1 was expressed by a high proportion of tissue-resident memory CD4 + T cells in both HIV-infected patients and non-HIV-infected patients. Our findings suggest that adipose tissue's intrinsic immunomodulatory properties may limit immune activation and thus may strongly contribute to viral persistence. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Family matters: The experiences and opinions of family members of persons with (severe) or profound intellectual disabilities

    OpenAIRE

    Luijkx, Jorien

    2016-01-01

    “I love my sister, but sometimes I don’t”. This is one of the statements made in the study focused on the experiences of family members of people with (profound) intellectual (and multiple) disabilities (both of individuals living in a residential facility as persons living at home). In recent years, there has been greater recognition of the important position of parents and siblings of people with (profound) intellectual (and multiple) disabilities and the importance of the wellbeing of all ...

  14. Profound hypoglycemia-ınduced by vaccinium corymbosum juice and laurocerasus fruit.

    Science.gov (United States)

    Aktan, Ahmet Hamdi; Ozcelik, Abdullah; Cure, Erkan; Cure, Medine Cumhur; Yuce, Suleyman

    2014-01-01

    An emergency intervention was performed in a 75-year-old male patient with hypoglycemic attack and blackout. Although he was diagnosed with prediabetes before 2 years, he did not take any anti-diabetic drug or follow dietary advice. He drank Vaccinium corymbosum L (VC) juice daily with a belief that it increases sexual potency. Before the development of hypoglycemia, the patient had consumed about 500 ml VC juice in addition to eating 200-300 gram of Laurocerasus officinalis (LO) fruit. The measured plasma glucose (PG) level during loss of consciousness was 30 mg/dl. The profound hypoglycemia may be an unexpected side effect of an interaction between the chemical compositions of the two plants, occurred as a result of LO fruit intake that may have a strong PG-lowering effect or related to excessive intake of VC juice. Both plants may be considered in the alternative treatment of diabetes.

  15. Basic life support and children with profound and multiple learning disabilities.

    Science.gov (United States)

    Cash, Stefan; Shinnick-Page, Andrea

    2008-10-01

    Nurses and other carers of people with learning disabilities must be able to manage choking events and perform basic life support effectively. UK guidelines for assessment of airway obstruction and for resuscitation do not take account of the specific needs of people with profound multiple learning disability. For example, they fail to account for inhibited gag and coughing reflexes, limited body movements or chest deformity. There are no national guidelines to assist in clinical decisions and training for nurses and carers. Basic life support training for students of learning disability nursing at Birmingham City University is supplemented to address these issues. The authors ask whether such training should be provided for all nurses including those caring for children and young people. They also invite comment and discussion on questions related to chest compression and training in basic life support for a person in a seated position.

  16. Hypothalamic obesity in patients with craniopharyngioma: Profound changes of several weight regulatory circuits

    Directory of Open Access Journals (Sweden)

    Christian eRoth

    2011-10-01

    Full Text Available One of the most striking examples of dysfunctional hypothalamic signaling of energy homeostasis is observed in patients with hypothalamic lesions leading to hypothalamic obesity (HO. This drastic condition is frequently seen in patients with craniopharyngioma (CP, an embryological tumor located in the hypothalamic and/or pituitary region, frequently causing not only hypopituitarism, but also leading to damage of medial hypothalamic nuclei due to the tumor and its treatment. HO syndrome in CP patients is characterized by fatigue, decreased physical activity, uncontrolled appetite, and morbid obesity, and is associated with insulin and leptin resistance. Mechanisms leading to the profoundly disturbed energy homeostasis are complex. This review summarizes different aspects of important clinical studies as well as data obtained in rodent studies. In addition a model is provided describing how medial hypothalamic lesion can interact simultaneously with several weight regulating circuitries.

  17. Profound vision loss impairs psychological well-being in young and middle-aged individuals

    Directory of Open Access Journals (Sweden)

    Garcia GA

    2017-02-01

    Full Text Available Giancarlo A Garcia,1,2 Matin Khoshnevis,1,3 Jesse Gale,1,4 Starleen E Frousiakis,1,5 Tiffany J Hwang,1,6 Lissa Poincenot,1 Rustum Karanjia,1,7–9 David Baron,6 Alfredo A Sadun1,7 1Doheny Eye Institute, Los Angeles, CA, USA; 2University of California, Irvine School of Medicine, Irvine, CA, USA; 3Department of Ophthalmology, Temple University, Philadelphia, PA, USA; 4Wellington School of Medicine and Health Sciences, University of Otago, Wellington, NZ; 5Department of Ophthalmology, New York Medical College, Valhalla, NY, USA; 6Department of Psychiatry & The Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 7Doheny Eye Centers, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles California, CA, USA; 8Department of Ophthalmology, University of Ottawa, Ottawa, ON, Canada; 9Ottawa Hospital Health Research Institute, Ottawa, ON, Canada Purpose: The aim of this study was to evaluate the effects of profound vision loss on psychological well-being in adolescents, young adults, and middle-aged adults with regard to mood, interpersonal interactions, and career-related goals. In addition, we assessed the significance of the resources that may be used to enhance psychological well-being in cases of profound vision loss, and in particular, examined the utility of low vision aids and the role of the ophthalmologist as a provider of emotional support.Methods: A questionnaire was issued to individuals aged 13–65 years with profound vision loss resulting from Leber’s hereditary optic neuropathy (LHON. Depression prevalence was evaluated with questions regarding major depressive disorder symptomatology. Participants appraised the effects of vision loss on their interpersonal interactions and career goals by providing an impact rating (IR on a 21-point psychometric scale from −10 to +10. Social well-being index was defined as the average of interpersonal IR and career IR

  18. Profound Endothelial Damage Predicts Impending Organ Failure and Death in Sepsis

    DEFF Research Database (Denmark)

    Johansen, Maria E; Johansson, Pär I.; Ostrowski, Sisse R

    2015-01-01

    levels at enrollment predicted risk of multiple organ failure during follow-up (HR [> 14 ng/mL vs. organ failure and death in septic......Endothelial damage contributes to organ failure and mortality in sepsis, but the extent of the contribution remains poorly quantified. Here, we examine the association between biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin [sTM], respectively......), organ failure, and death in sepsis. The data from a clinical trial, including critically ill patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were studied. Syndecan-1 and sTM levels at the time of study enrollment were determined. The predictive ability of biomarker levels...

  19. Outcomes of laryngohyoid suspension techniques in an ovine model of profound oropharyngeal dysphagia.

    Science.gov (United States)

    Johnson, Christopher M; Venkatesan, Naren N; Siddiqui, M Tausif; Cates, Daniel J; Kuhn, Maggie A; Postma, Gregory M; Belafsky, Peter C

    2017-12-01

    To evaluate the efficacy of various techniques of laryngohyoid suspension in the elimination of aspiration utilizing a cadaveric ovine model of profound oropharyngeal dysphagia. Animal study. The head and neck of a Dorper cross ewe was placed in the lateral fluoroscopic view. Five conditions were tested: baseline, thyroid cartilage to hyoid approximation (THA), thyroid cartilage to hyoid to mandible (laryngohyoid) suspension (LHS), LHS with cricopharyngeus muscle myotomy (LHS-CPM), and cricopharyngeus muscle myotomy (CPM) alone. Five 20-mL trials of barium sulfate were delivered into the oropharynx under fluoroscopy for each condition. Outcome measures included the penetration aspiration scale (PAS) and the National Institutes of Health (NIH) Swallow Safety Scale (NIH-SSS). Median baseline PAS and NIH-SSS scores were 8 and 6, respectively, indicating severe impairment. THA scores were not improved from baseline. LHS alone reduced the PAS to 1 (P = .025) and NIH-SSS to 2 (P = .025) from baseline. LHS-CPM reduced the PAS to 1 (P = .025) and NIH-SSS to 0 (P = .025) from baseline. CPM alone did not improve scores. LHS-CPM displayed improved NIH-SSS over LHS alone (P = .003). This cadaveric model represents end-stage profound oropharyngeal dysphagia such as what could result from severe neurological insult. CPM alone failed to improve fluoroscopic outcomes in this model. Thyrohyoid approximation also failed to improve outcomes. LHS significantly improved both PAS and NIH-SSS. The addition of CPM to LHS resulted in improvement over suspension alone. NA. Laryngoscope, 127:E422-E427, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  20. Proteome analysis demonstrates profound alterations in human dendritic cell nature by TX527, an analogue of vitamin D

    DEFF Research Database (Denmark)

    Ferreira, G. B.; van Etten, E.; Lage, K.

    2009-01-01

    Structural analogues of vitamin D have been put forward as therapeutic agents able to exploit the immunomodulatory effects of vitamin D, without its undesired calcemic side effects. We have demonstrated that TX527 affects dendritic cell (DC) maturation in vitro, resulting in the generation...... of a tolerogenic cell. In the present study, we aimed to explore the global protein changes induced by the analogue in immature DC (iDC) and mature human DC and to correlate them with alterations in DC morphology and function. Human CD14(+) monocytes were differentiated toward iDC or mature DCs, in the presence...

  1. Immunomodulatory activities of different solvent extracts from Tricholoma matsutake (S. Ito et S. Imai) singer (higher basidiomycetes) on normal mice.

    Science.gov (United States)

    Yin, Xiulian; You, Qinghong; Jiang, Zhonghai

    2012-01-01

    The immunomodulatory activities of different solvent extracts from the culinary-medicinal mushroom Tricholoma matsutake were studied in vivo in normal mice. The extracts were prepared using different solvents in an order of increasing polarity. The immunomodulatory activities were investigated by measuring the thymus and spleen index, phagocytic rate of macrophage phagocytosis, delayed-type hypersensitivity, plaque-forming cell, and proliferation of splenocytes. Results demonstrated that water extract (WE) and n-butyl alcohol extract (BAE) of T. matsutake could enhance the immunity of mice significantly compared with the control group. Main components of WE and BAE were polysaccharides, proteins, and flavonoids; we presume that these may be the main immunomodulating and immuno-enhancing agents in T. matsutake.

  2. Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM.

    Directory of Open Access Journals (Sweden)

    Patrícia Kellen Martins Oliveira Brito

    Full Text Available Toll-like receptors (TLR contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from Artocarpus heterophyllus interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c. ArtinM (0.5 μg in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naïve BALB/c mice. The mice were s.c. injected twice (7 days interval with ArtinM (0.5, 1.0, 2.5, or 5.0 μg, LPS (positive control, or PBS (negative control and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 μg. Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ≥2.5 μg. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-γ, TNF-α, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 μg ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naïve mice, whereas the relative expressions of T-bet, GATA-3, and ROR-γt were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naïve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naïve mice.

  3. Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

    Science.gov (United States)

    Oliveira Brito, Patrícia Kellen Martins; Gonçalves, Thiago Eleutério; Fernandes, Fabrício Freitas; Miguel, Camila Botelho; Rodrigues, Wellington Francisco; Lazo Chica, Javier Emílio; Roque-Barreira, Maria Cristina

    2017-01-01

    Toll-like receptors (TLR) contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from Artocarpus heterophyllus interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c.) ArtinM (0.5 μg) in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naïve BALB/c mice. The mice were s.c. injected twice (7 days interval) with ArtinM (0.5, 1.0, 2.5, or 5.0 μg), LPS (positive control), or PBS (negative control) and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 μg). Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ≥2.5 μg. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB) and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-γ, TNF-α, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 μg ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naïve mice, whereas the relative expressions of T-bet, GATA-3, and ROR-γt were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naïve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naïve mice. PMID:29084277

  4. Immunomodulatory effects of royal jelly on aorta CD3, CD68 and eNOS expression in hypercholesterolaemic rats

    Directory of Open Access Journals (Sweden)

    Amal Attia El-Morsy Ibrahim

    2014-08-01

    RJ administration (300 mg/kg/day with CH, produced a counteractive effect, represented in recompense of biochemical alteration, CD4 and CD8 expression. RJ intake also amended the histological picture. The immunohistochemical picture revealed a decrease in CD3, CD86 and eNOS in the aortic tissue. These findings attributed to the significant immunomodulatory effect of RJ remedy suppress deleterious effects of hypercholesterolaemia.

  5. Immunomodulatory response of mice splenocytes induced by RcaL, a lectin isolated from cobia fish (Rachycentron canadum) serum.

    Science.gov (United States)

    Coriolano, Marília Cavalcanti; Silva, Cynarha Daysy Cardoso da; Melo, Cristiane Moutinho Lagos de; Bezerra, Ranilson de Souza; Santos, Athiê Jorge Guerra; Pereira, Valéria Rêgo Alves; Coelho, Luana Cassandra Breitenbach Barroso

    2012-11-01

    This work reports the isolation of a serum lectin from cobia fish (Rachycentron canadum) named RcaL. Immunomodulatory activity on mice splenocyte experimental cultures through cytotoxic assays and cytokine production were also performed. RcaL was obtained through precipitation with ammonium sulphate and affinity chromatography on a Concanavalin A-Sepharose 4B column. The ammonium sulphate fraction F3 showed the highest specific hemagglutinating activity and was applied to affinity chromatography. The lectin was eluted with methyl-α-D-mannopyranoside. RcaL showed highest affinity for methyl-α-D-mannopyranoside and D-mannose; eluted fractions of RcaL agglutinated rabbit erythrocytes (titre, 128(-1)) retained 66 % of chromatographed lectin activity, and the obtained purification factor was 1.14. Under reducing conditions, a polypeptide band of 19.2 kDa was revealed in sodium dodecyl sulphate polyacrylamide gel electrophoresis (PAGE). PAGE confirmed RcaL as an acidic protein revealed in a single band. Cytotoxic and immunomodulatory assays with RcaL in mice splenocyte cultures showed that the lectin was not cytotoxic and induced higher interferon gamma and nitric oxide production in splenocyte cultures. Purified RcaL induced preferential Th1 response, suggesting that it acts as an immunomodulatory compound.

  6. Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacterium longum.

    Science.gov (United States)

    Lee, Jung-Woo; Shin, Jung-Gul; Kim, Eun Hee; Kang, Hae Eun; Yim, In Been; Kim, Ji Yeon; Joo, Hong-Gu; Woo, Hee Jong

    2004-03-01

    The immunomodulatory and antitumor effects of lactic acid bacteria (LABs) were investigated. Cytoplasmic fraction of Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium longum were tested for the antiproliferative activity in vitro to SNUC2A, SNU1, NIH/3T3 and Jurkat cell lines by crystal violet assay. All cytoplasmic fraction suppressed proliferation of tumor cells, though L. casei and B. longum were more effective. From these results, cytoplasmic fraction of L. casei and B. longum with Y400 as a control were administered as dietary supplements to Balb/c mice for 2, and 4 consecutive wks. Administration for 4 wks enhanced the number of total T cells, NK cells and MHC class II+ cells, and CD4-CD8+ T cells in flow cytometry analysis. To determine of antitumor activity of LABs preparation in vivo, F9 teratocarcinoma cells were inoculated on mice at 14th day. Body weight was decreased with increased survival rate in all groups with the cytoplasm of LABs. Our results showed that cytoplasmic fraction of LABs had direct antiproliferative effects on tumor cell lines in vitro, effects on immune cells in vivo, and antitumor effects on tumor-bearing mice with prolonged survival periods.

  7. Immunomodulatory and Physical Effects of Oil Composition in Vaccine Adjuvant Emulsions

    Science.gov (United States)

    Fox, Christopher B.; Baldwin, Susan L.; Duthie, Malcolm S.; Reed, Steven G.; Vedvick, Thomas S.

    2011-01-01

    Squalene-based oil-in-water emulsions have been used for years in some seasonal and pandemic influenza vaccines. However, concerns have been expressed regarding squalene source and potential biological activities. Little information is available regarding the immunomodulatory activity of squalene in comparison with other metabolizable oils in the context of oil-in-water emulsions formulated with vaccines. The present work describes the manufacture and physical characterization of emulsions composed of different classes of oils, including squalene, long chain triglycerides, a medium chain triglyceride, and a perfluorocarbon, all emulsified with egg phosphatidylcholine. Some differences were apparent among the non-squalene oils in terms of emulsion stability, including higher size polydispersity in the perfluorocarbon emulsion, more rapid visual instability at 60 °C for the long-chain triglyceride and perfluorocarbon emulsions, and an increased creaming rate in the medium-chain triglyceride emulsion at 60 °C as detected by laser scattering optical profiling. The biological activity of each of these emulsions was compared when formulated with either a recombinant malaria antigen or a split-virus inactivated influenza vaccine. Overall, vaccines containing the squalene emulsion elicited higher antibody titers and more abundant long-lived plasma cells than vaccines containing emulsions based on other oils. Since squalene-based emulsions show higher adjuvant potency compared to the other oils tested, non-squalene oils may be more suitable as carriers of amphiphilic or hydrophobic immunostimulatory molecules (such as TLR agonists) rather than as stand-alone adjuvants. PMID:21906648

  8. The immunomodulatory effects of shark cartilage on the mouse and human immune system

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    ali Sheikhian

    2007-01-01

    Materials and methods: In an experimental study, the effects of different doses of shark cartilage on humoral (antibody titer immune response against sheep red blood cells (SRBC, were measured in mouse. In addition, we evaluated the modulatory effects of the shark cartilage on the natural killer (NK activity of the peritoneal cells of mouse against a tumor cell line called K562, according to the standard methods. The proliferative response of the human peripheral blood mononuclear cells was measured under the influence of shark cartilage. Results: Pure shark cartilage enhanced antibody response against SRBC in vivo. The hemagglutination titer which was 1/147 in the control group (injected with hen cartilage, increased to 1/1355 in the test group. The optimal dose was 100 mg/ml. both type of cartilage had blastogenic effect on peripheral blood mononuclear cells (the blastogenic index was 6.7 and 4.9 for impure shark cartilage and hen cartilage, respectively. NK activity was inhibited completely by pure shark cartilage (the amount of the killing activity of the effector peritoneal cells for the control and test groups against target cells was 25.9% and 5.5% respectively. Conclusion: Shark cartilage has a potent immunomodulatory effect on the specific immune mechanisms and some inhibitory effects on the innate immune mechanisms such as NC activity. Since the specific immunity has a more pivotal role against tumor formation, shark cartilage can be used as a cancer immunotherapeutic.

  9. Ultraviolet Radiation and the Slug Transcription Factor Induce Proinflammatory and Immunomodulatory Mediator Expression in Melanocytes

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    Stephanie H. Shirley

    2012-01-01

    Full Text Available Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete proinflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce proinflammatory mediators and that Slug is important in this process. Microarray studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of proinflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

  10. Immunomodulatory Effects of Deokgu Thermomineral Water Balneotherapy on Oxazolone-Induced Atopic Dermatitis Murine Model.

    Science.gov (United States)

    Lee, Young Bok; Kim, Su Jin; Park, Sae Mi; Lee, Kyung Ho; Han, Hyung Jin; Yu, Dong Soo; Woo, So Youn; Yun, Seong Taek; Hamm, Se-Yeong; Kim, Hong Jig; Kim, Jin-Wou

    2016-04-01

    Although the therapeutic mechanism of balneotherapy for atopic dermatitis has not been clarified, many atopic patients who visit thermomineral springs have shown clinical improvements. This study was aimed to evaluate the immunomodulatory effect of thermomineral water balneotherapy on the atopic dermatitis murine model. The oxazolone-induced atopic dermatitis murine model was used to evaluate the therapeutic effect of balneotherapy with Deokgu thermomineral water compared with distilled water. Histologic evaluation and confocal microscopic imaging were performed to analyze the lesional expression of cluster-of-differentiation (CD)4 and forkhead box p3 (Foxp3). Lesional mRNA expression of interleukin (IL) 33, thymic stromal lymphopoietin (TSLP), and Foxp3 was evaluated by real-time reverse transcription polymerase chain reaction. Compared with the distilled water bath group, confocal microscopic evaluation of CD4 and Foxp3 merged images showed increased expression of regulatory T cells in the thermomineral balneotherapy group. The lesional mRNA level of IL-33 showed a reduced trend in the thermomineral balneotherapy group, whereas the level of mRNA of Foxp3 was increased. TSLP showed a decreased trend in both distilled water and thermomineral water bath groups. There was a trend of reduced expression in lesional IL-33 mRNA but increased cell count of CD4(+) Foxp3(+) regulatory T cells in thermomineral balneotherapy compared with distilled water bath. Therefore, thermomineral balneotherapy can be an effective and safe adjuvant therapeutic option for atopic dermatitis.

  11. Immunomodulatory constituents of human milk change in response to infant bronchiolitis.

    Science.gov (United States)

    Bryan, Dani-Louise; Hart, Prue H; Forsyth, Kevin D; Gibson, Robert A

    2007-09-01

    Although epidemiological evidence is generally supportive of a causal association between respiratory syncytial virus (RSV) bronchiolitis during infancy and the development of persistent wheeze/asthma, if not allergy, the mechanism by which this occurs and an explanation for why all children do not succumb remains to be elucidated. Breast feeding has been found to confer a protective effect against respiratory infections such as RSV bronchiolitis and allergy; however, again there is little direct evidence and no clear mechanism. In this study, we examined whether human milk immunomodulatory factors (cells, cytokines) change in response to clinically diagnosed, severe bronchiolitis in the recipient breast-fed infant. We examined milk from 36 breast feeding mothers of infants hospitalized with bronchiolitis and compared them with milk from 63 mothers of postpartum age-matched healthy controls. Milks from mothers of infants hospitalized with bronchiolitis had significantly greater numbers of viable cells when compared with the milks obtained from mothers of healthy infants (1.3 +/- 0.4 vs. 0.3 +/- 0.03 x 10(6) cells/ml, mean +/- s.e.m.; p respiratory infections as well as a possible contributing factor to the development of persistent wheeze in these infants.

  12. Immunomodulatory Effects of CP-25 on Splenic T Cells of Rats with Adjuvant Arthritis.

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    Wang, Yang; Han, Chen-Chen; Cui, Dongqian; Luo, Ting-Ting; Li, Yifan; Zhang, Yuwen; Ma, Yang; Wei, Wei

    2018-06-01

    Rheumatoid arthritis (RA) is an autoimmune disease in which T cells play an important role. Paeoniflorin-6-oxy-benzenesulfonate (CP-25) shows a strong anti-inflammatory and immunomodulatory effect in the joint of adjuvant arthritis (AA) rats, but the role of the spleen function is still unclear. The aim of this study was to research how CP-25 regulated spleen function of AA rats. Male Sprague-Dawley rats were administered with CP-25 (50 mg/kg) orally from day 17 to 29 after immunization. The spleen histopathological changes were analyzed by hematoxylin-eosin staining. G protein-coupled receptor kinases (GRKs) and prostaglandin receptor subtypes (EPs) were screened by Western blot and immunohistochemistry. The co-expression of GRK2 and EP2 as well as GRK2 and EP4 was measured by immunofluorescence and co-immunoprecipitation. The expression of GRK2 and EP4 in splenic T cells was further detected by immunofluorescence. CP-25 was found to relieve the secondary paw swelling, attenuate histopathologic changes, and downregulate GRK2, EP2 and EP4 expression in AA rats. Additionally, CP-25 not only downregulated the co-expression of GRK2 and EP4 but also downregulated GRK2, EP4 expression in splenic T cells of AA rats. From these results, we can infer that CP-25 play an anti-inflammatory and immune function by affecting the function of the splenic T cells.

  13. Ultraviolet Radiation and the Slug Transcription Factor Induce Pro inflammatory and Immunomodulatory Mediator Expression in Melanocytes

    International Nuclear Information System (INIS)

    Shirley, S. H.; Kusewitt, D. F.; Grimm, E. A.

    2012-01-01

    Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR) component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete pro inflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce pro inflammatory mediators and that Slug is important in this process. Micro array studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of pro inflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

  14. Screening of immunomodulatory activity of total and protein extracts of some Moroccan medicinal plants.

    Science.gov (United States)

    Daoudi, Abdeljlil; Aarab, Lotfi; Abdel-Sattar, Essam

    2013-04-01

    Herbal and traditional medicines are being widely used in practice in many countries for their benefits of treating different ailments. A large number of plants in Morocco were used in folk medicine to treat immune-related disorders. The objective of this study is to evaluate the immunomodulatory activity of protein extracts (PEs) of 14 Moroccan medicinal plants. This activity was tested on the proliferation of immune cells. The prepared total and PEs of the plant samples were tested using MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) assay on the splenocytes with or without stimulation by concanavalin-A (Con-A), a mitogenic agent used as positive control. The results of this study indicated different activity spectra. Three groups of activities were observed. The first group represented by Citrullus colocynthis, Urtica dioica, Elettaria cardamomum, Capparis spinosa and Piper cubeba showed a significant immunosuppressive activity. The second group that showed a significant immunostimulatory activity was represented by Aristolochia longa, Datura stramonium, Marrubium vulgare, Sinapis nigra, Delphynium staphysagria, Lepidium sativum, Ammi visnaga and Tetraclinis articulata. The rest of the plant extracts did not alter the proliferation induced by Con-A. This result was more important for the PE than for the total extract. In conclusion, this study revealed an interesting immunomodulating action of certain PEs, which could explain their traditional use. The results of this study may also have implications in therapeutic treatment of infections, such as prophylactic and adjuvant with cancer chemotherapy.

  15. IMMUNOMODULATORY ACTION OF MYELOPIDUM UNDER ITS INCLUSION IN COMPLEX THERAPY OF PATIENTS WITH PENETRATING OCULAR INJURIES

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    T. V. Gavrilova

    2008-01-01

    Full Text Available Abstract. Examination of immunomodulatory actions and clinical efficiency of myelopidum when included into complex therapy that was carried out in 24 male patients with severe (stage 3 penetrating eye injury in the course of trauma treatment. The levels of C-reactive protein, lactoferrin, interleukin (IL-1β, IL-6, and activity of complement system were measured in peripheral blood, and concentrations of lactoferrin and IL-8 were determined in tears. An increase in lactoferrin, C-reactive protein, IL-1β, IL-8, and C5 complement component levels was detected during early post-traumatic period, as compared with data from the control group. As compared to effects of steroid and non-steroid anti-inflammatory drugs included into standard therapy, treatment with myelopidum has led to a more favorable clinical course of traumatic process, and resulted into more pronounced anti-inflammatory effect that was manifested by decrease in lactoferrin and C-reactive protein levels, reduction of IL-1β concentration, and C5 complement component activity. (Med. Immunol., 2008, vol. 10, N 2-3, pp 239-244.

  16. Structural characterization and immunomodulatory activity of a pectic polysaccharide (CALB-4) from Fructus aurantii.

    Science.gov (United States)

    Shu, Zunpeng; Yang, Yanni; Xing, Na; Wang, Yi; Wang, Qiuhong; Kuang, Haixue

    2018-02-01

    A purified polysaccharide, designated CALB-4, was acquired from Fructus aurantii that is the traditional edible/medicina plant in China. The present study was performed to characterize the CALB-4 and to evaluate its immunomodulatory activities on human peripheral blood mononuclear cells (PBMCs). The structure of CALB-4 was characterized by partial acid hydrolysis, periodate oxidation, Smith degradation, and methylation analysis combined with gas chromatography-mass spectrometry (GC-MS), Infrared Spectroscopy (IR) and scanning electron microscopy (SEM). The results indicated that CALB-4 was elucidated as a pectic polysaccharide and its main chain is composed of Man, Gal UA and Gal, interspersed with Ara, Rha, Man and Gal. Furthermore, immunological tests showed that CALB-4 exhibits the immunoenhancement effects. The mechanism for this action might be attributed to the increase of the cytoplasmic concentration of pro-IL-1 via the up-regulation of several mitogen-activated protein kinases (MAPKs) and the nuclear translocation of p65. This study clarified that CALB-4 could be as an efficacious biological response modifier in immunotherapy. Copyright © 2018. Published by Elsevier B.V.

  17. Immunomodulatory Effects of Diterpene Quinone Derivatives from the Roots of Horminum pyrenaicum in Human PBMC

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    K. Becker

    2018-01-01

    Full Text Available Several phytochemicals were shown to interfere with redox biology in the human system. Moreover, redox biochemistry is crucially involved in the orchestration of immunological cascades. When screening for immunomodulatory compounds, the two interferon gamma- (IFN-γ- dependent immunometabolic pathways of tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1 and neopterin formation by GTP-cyclohydrolase 1 (GTP-CH-I represent prominent targets, as IFN-γ-related signaling is strongly sensitive to oxidative triggers. Herein, the analysis of these pathway activities in human peripheral mononuclear cells was successfully applied in a bioactivity-guided fractionation strategy to screen for anti-inflammatory substances contained in the root of Horminum (H. pyrenaicum L. (syn. Dragon’s mouth, the only representative of the monophyletic genus Horminum. Four abietane diterpene quinone derivatives (horminone, 7-O-acetylhorminone, inuroyleanol and its 15,16-dehydro-derivative, a novel natural product, two nor-abietane diterpene quinones (agastaquinone and 3-deoxyagastaquinone and two abeo 18 (4 → 3 abietane diterpene quinones (agastol and its 15,16-dehydro-derivative could be identified. These compounds were able to dose-dependently suppress the above mentioned pathways with different potency. Beside the description of new active compounds, this study demonstrates the feasibility of integrating IDO-1 and GTP-CH-I activity in the search for novel anti-inflammatory compounds, which can then be directed towards a more detailed mode of action analysis.

  18. Antiplasmodial, antioxidant and immunomodulatory activities of ethanol extract of Vernonia amygdalina del. Leaf in Swiss mice

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    Ehimwenma Omoregie

    2016-03-01

    Full Text Available Objective: Vernonia amygdalina (V.  amygdalina leaf is locally employed in the Southern region of Nigeria in the treatment of malari a infection. This study evaluated the in vivo antiplasmodial, antioxidant and immunomodulatory effect of ethanol extract of V.  amygdalina leaf. Materials and Methods: The active principles of the dried leaf were extracted with ethanol. For quality validation, chemical finger-print of the extract was performed through high performance thin layer chromatography (HPTLC. The extract was assessed for antiplasmodial activity by the standard four-day suppressive test on Plasmodium berghei (ANKA infected male Swiss mice (six weeks old placed into five groups of six animals each. Result: The absorption spectra from the HPTLC revealed several peaks suggesting presence of some bioactive compounds. Results from the in vivo study showed that the ethanol extract of the plant leaf was significantly active against P. berghei in a dose-dependent manner with the minimum and maximum activity observed in the mice treated orally with 100mg/kg (% inhibition of 23.7% and 1000 mg/kg (% inhibition of 82.3 % of the extract, respectively, on day four of the study. There was also a dose-dependent decrease (p

  19. Dietary Chlorella vulgaris Ameliorates Altered Immunomodulatory Functions in Cyclophosphamide-Induced Immunosuppressive Mice

    Science.gov (United States)

    Cheng, Dai; Wan, Zhaodong; Zhang, Xinyu; Li, Jian; Li, He; Wang, Chunling

    2017-01-01

    Based on the well-known toxicity of cyclophosphamide (CYP) on the immune system, this research investigated the modulating effects of the long-term dietary Chlorella vulgaris (CV) supplementation on the immunosuppression induced by CYP in mice, in order to provide a novel dietary design to mitigate the side effects of CYP therapy. Control, CYP-treated, CYP + CV (6%), CYP + CV (12%) and CYP + CV (24%) were used for 6 weeks, CV supplement in diet recovered the significantly reduced immunological function in CYP treated mice. As CV may have a modulating function through the inducible expression of cytokines, we assayed the expressions of interleukin-2 (IL-2), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Our results suggested that CYP significantly reduced the lymphocytes proliferation and phagocytic activities of macrophages, and stimulated the production of IL-2, IL-12, TNF-α and IFN-γ and that this impairment has been successfully adjusted by CV supplementation. Treatment with the algae also enhanced the natural killer (NK) cells cytotoxicity, and ameliorate histological changes of the spleen in CYP-treated mice. Therefore, as we found in this study, a diet supplemented with whole CV has beneficial effects on CVP-induced immunosuppression, through its immunomodulatory potential. PMID:28684674

  20. The Immunomodulatory Small Molecule Imiquimod Induces Apoptosis in Devil Facial Tumour Cell Lines.

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    Amanda L Patchett

    Full Text Available The survival of the Tasmanian devil (Sarcophilus harrisii is threatened by devil facial tumour disease (DFTD. This transmissible cancer is usually fatal, and no successful treatments have been developed. In human studies, the small immunomodulatory molecule imiquimod is a successful immunotherapy, activating anti-tumour immunity via stimulation of toll-like receptor-7 (TLR7 signaling pathways. In addition, imiquimod is a potent inducer of apoptosis in human tumour cell lines via TLR7 independent mechanisms. Here we investigate the potential of imiquimod as a DFTD therapy through analysis of treated DFTD cell lines and Tasmanian devil fibroblasts. WST-8 proliferation assays and annexin V apoptosis assays were performed to monitor apoptosis, and changes to the expression of pro- and anti-apoptotic genes were analysed using qRT-PCR. Our results show that DFTD cell lines, but not Tasmanian devil fibroblasts, are sensitive to imiquimod-induced apoptosis in a time and concentration dependent manner. Induction of apoptosis was accompanied by down-regulation of the anti-apoptotic BCL2 and BCLXL genes, and up-regulation of the pro-apoptotic BIM gene. Continuous imiquimod treatment was required for these effects to occur. These results demonstrate that imiquimod can deregulate DFTD cell growth and survival in direct and targeted manner. In vivo, this may increase DFTD vulnerability to imiquimod-induced TLR7-mediated immune responses. Our findings have improved the current knowledge of imiquimod action in tumour cells for application to both DFTD and human cancer therapy.

  1. Immunomodulatory effects of the aromatic geranyl derivative filifolinone tested by the induction of cytokine expression.

    Science.gov (United States)

    Valenzuela, Beatriz; Imarai, Mónica; Torres, René; Modak, Brenda

    2013-12-01

    Fish farming crops are constantly exposed to infectious diseases due to intensive production conditions under which microorganisms develop and spread easily, resulting in severe economic losses. The massive use of antibiotics to control these diseases has lead to the accumulation of residues and the development of drug resistance. Consequently, it is urgent to develop new pharmacological tools to stimulate protective immune responses in salmonids to combat infectious diseases. We evaluated the immunostimulant activity of terpenoid derivatives isolated from species of the Heliotropium genus, which had previously shown antiviral activity in salmon. The immunomodulatory effects of the 3 H-spiro [1-benzofuran-2,1'-ciclohexane] derivative called filifolinone, were studied in vitro using the SHK-1 cell line derived from leucocytes of salmon head kidney and in vivo in Atlantic salmon. For the evaluation, we studied the effect of this compound in the expression of various cytokines. The results showed that Filifolinone increases the levels of expression of pro-inflammatory and anti-inflammatory cytokines. This suggests that Filifolinone is a potential alternative immunomodulator for veterinary purposes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma

    International Nuclear Information System (INIS)

    Hideshima, T; Cottini, F; Ohguchi, H; Jakubikova, J; Gorgun, G; Mimura, N; Tai, Y-T; Munshi, N C; Richardson, P G; Anderson, K C

    2015-01-01

    Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi) also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger significant MM cell growth inhibition by inhibiting or downregulating c-Myc. Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity, associated with downregulation of c-Myc. Unexpectedly, we observed that decreased levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len shows less efficacy than simultaneous treatment with this combination. Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs, together with Len induces synergistic MM cytotoxicity without alteration of CRBN expression. Our results showed that only modest class-I HDAC inhibition is able to induce synergistic MM cytotoxicity in combination with Len. These studies may provide the framework for utilizing HDACi in combination with Len to both avoid CRBN downregulation and enhance anti-MM activities

  3. Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma.

    Science.gov (United States)

    Hideshima, T; Cottini, F; Ohguchi, H; Jakubikova, J; Gorgun, G; Mimura, N; Tai, Y-T; Munshi, N C; Richardson, P G; Anderson, K C

    2015-05-15

    Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi) also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger significant MM cell growth inhibition by inhibiting or downregulating c-Myc. Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity, associated with downregulation of c-Myc. Unexpectedly, we observed that decreased levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len shows less efficacy than simultaneous treatment with this combination. Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs, together with Len induces synergistic MM cytotoxicity without alteration of CRBN expression. Our results showed that only modest class-I HDAC inhibition is able to induce synergistic MM cytotoxicity in combination with Len. These studies may provide the framework for utilizing HDACi in combination with Len to both avoid CRBN downregulation and enhance anti-MM activities.

  4. The Immunomodulatory Effect of You-Gui-Wan on Dermatogoides-pteronyssinus-Induced Asthma

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    Li-Jen Lin

    2012-01-01

    Full Text Available The traditional Chinese medicine You-Gui-Wan (YGW contains ten species of medicinal plants and has been used to improve health in remissive states of asthma for hundreds of years in Asia. However, little is known about the immunomodulatory mechanisms in vivo. Therefore, this study investigated the pathologic and immunologic responses to YGW in mice that had been repeatedly exposed to Dermatogoides-pteronyssinus (Der p. YGW reduced Der-p-induced airway hyperresponsiveness and total IgE in serum. It also inhibited eosinophil infiltration by downregulating the protein expression of IL-5 in serum and changed the Th2-bios in BALF by upregulating IL-12. Results of the collagen assay and histopathologic examination showed that YGW reduced airway remodeling in the lung. In addition, after YGW treatment there was a relative decrease in mRNA expression of TGF-β1, IL-13, eotaxin, RANTES, and MCP-1 in lung in the YGW group. The results of EMSA and immunohistochemistry revealed that YGW inhibited NF-κB expression in epithelial lung cells. YGW exerts its regulative effects in chronic allergic asthmatic mice via its anti-inflammatory activity and by inhibiting the progression of airway remodeling.

  5. Survival, Intestinal Mucosa Adhesion, and Immunomodulatory Potential of Lactobacillus plantarum Strains.

    Science.gov (United States)

    Santarmaki, Valentini; Kourkoutas, Yiannis; Zoumpopoulou, Georgia; Mavrogonatou, Eleni; Kiourtzidis, Mikis; Chorianopoulos, Nikos; Tassou, Chrysoula; Tsakalidou, Effie; Simopoulos, Constantinos; Ypsilantis, Petros

    2017-09-01

    Survival during transit through the gastrointestinal track, intestinal mucosa adhesion, and a potential immunomodulatory effect of Lactobacillus plantarum strains 2035 and ACA-DC 2640 were investigated in a rat model. According to microbiological and multiplex PCR analysis, both strains were detected in feces 24 h after either single-dose or daily administration for 7 days. Intestinal mucosa adhesion of L. plantarum 2035 was noted in the large intestine at 24 h after single-dose administration, while it was not detected at 48 h. Daily dosing, prolonged detection of the strain up to 48 h post-administration, and expanded adhesion to the small intestine. Adhesion of L. plantarum ACA-DC 2640 to the intestinal mucosa after single-dose administration was prolonged and more extended compared to L. plantarum 2035. Daily dosing increased both the levels and the rate of positive cultures of the strains compared to those of the single-dose scheme. In addition, both strains increased total IgG while decreased IgM and IgA serum levels. In conclusion, L. plantarum 2035 and L. plantarum ACA-DC 2640 survived transit through the gastrointestinal track, exhibited transient distinct adhesion to the intestinal mucosa and modulated the systemic immune response.

  6. Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent.

    Science.gov (United States)

    Ilan, Yaron; Elstein, Deborah; Zimran, Ari

    2009-10-01

    Gaucher disease (GD) is caused by the reduced activity of a lysosomal enzyme, glucocerebrosidase, leading to the accumulation of glucocerebroside (GC). The relatively high prevalence of this disease within an ethnic group is believed to reflect a selective advantage. Treatment with enzyme replacement therapy (ERT) is safe and effective in ameliorating the primary symptoms of the disease, yet there have been reports that some patients on ERT have developed type 2 diabetes or metabolic syndrome, malignancies and central nervous system disorders. A series of animal studies suggest that these complications may be related to the reduction of GC levels by the enzyme administered. GC has been shown to have an immunomodulatory effect through the promotion of dendritic cells, natural killer T cells, and regulatory T cells. The break down of GC to ceramide can underline part of these findings. Clinical trials suggested a beneficial effect of GC in type 2 diabetes or nonalcoholic steatohepatitis. This review of the data from animal models and humans proposes that the increased level of GC may provide an evolutionary advantage for patients with GD. Indirectly, these data support treating symptomatic patients with mild/moderate GD with low-dose ERT and re-evaluating the use of ERT in asymptomatic patients.

  7. Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude.

    Science.gov (United States)

    Teixeira, Marcus Zulian

    2016-11-01

    Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  8. Dextrans produced by lactic acid bacteria exhibit antiviral and immunomodulatory activity against salmonid viruses.

    Science.gov (United States)

    Nácher-Vázquez, Montserrat; Ballesteros, Natalia; Canales, Ángeles; Rodríguez Saint-Jean, Sylvia; Pérez-Prieto, Sara Isabel; Prieto, Alicia; Aznar, Rosa; López, Paloma

    2015-06-25

    Viral infections in the aquaculture of salmonids can lead to high mortality and substantial economic losses. Thus, there is industrial interest in new molecules active against these viruses. Here we describe the production, purification, and the physicochemical and structural characterization of high molecular weight dextrans synthesized by Lactobacillus sakei MN1 and Leuconostoc mesenteroides RTF10. The purified dextrans, and commercial dextrans with molecular weights ranging from 10 to 2000kDa, were assayed in infected BF-2 and EPC fish cell-line monolayers for antiviral activity. Only T2000 and dextrans from MN1 and RTF10 had significant antiviral activity. This was similar to results obtained against infectious pancreatic necrosis virus. However the dextran from MN1 showed ten-fold higher activity against hematopoietic necrosis virus than T2000. In vivo assays using the MN1 polymer confirmed the in vitro results and revealed immunomodulatory activity. These results together with the high levels of dextran production (2gL(-1)) by Lb. sakei MN1, indicate the compounds potential utility as an antiviral agent in aquaculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

    Directory of Open Access Journals (Sweden)

    Richard Heyes

    2016-01-01

    Full Text Available This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs in promoting vascularized composite allotransplant (VCA tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human populations undergoing solid organ transplant were also identified and reviewed. Sixteen preclinical studies are included. Eleven studies compared MSC monotherapy to no therapy; of these, ten reported improved graft survival, which was statistically significantly prolonged in eight. Eight studies analyzed allograft survival with MSC therapy as an adjunct to proven immunosuppressive regimens. In these studies, daily immunosuppression was transiently delivered and then stopped. In all studies, treatment-free graft survival was statistically significantly prolonged in animals that received MSC therapy. MSCs have been safely administered clinically and their use in renal transplant clinical trials provides evidence that they improve allograft transplant tolerance in clinical practice. There is potential for MSC induction therapy to overcome many of the obstacles to widespread VCA in clinical practice. Preclinical studies are needed before MSC-induced VCA tolerance becomes a clinical reality.

  10. Effectiveness of the immunomodulatory extract of Kalanchoe pinnata against murine visceral leishmaniasis.

    Science.gov (United States)

    Gomes, D C O; Muzitano, M F; Costa, S S; Rossi-Bergmann, B

    2010-04-01

    Previously, we described the protective action of the immunomodulatory extract of Kalanchoe pinnata (Kp) in murine and human cutaneous leishmaniasis. In the present study, we investigated the effectiveness of Kp against visceral leishmaniasis, using the BALB/c mouse model of infection with Leishmania chagasi. Mice receiving oral daily doses of Kp (400 mg/kg) for 30 days displayed significantly reduced hepatic and splenic parasite burden, when compared with untreated animals. Protectiveness was accompanied by a reduction in parasite-specific IgG serum levels, and impaired capacity of spleen cells to produce IL-4, but not IFN-gamma and nitric oxide upon antigen recall in vitro. The reference drug Pentostam (72 mg/kg) given by the intra-peritoneal route on alternate days produced an anti-leishmanial effect similar to oral Kp. Our findings show that the oral efficacy of Kp, seen previously in murine cutaneous leishmaniasis, extends also to visceral leishmaniasis caused by L. chagasi, a difficult to treat and lethal disease of man.

  11. Structure characterization of a novel polysaccharide from Hericium erinaceus fruiting bodies and its immunomodulatory activities.

    Science.gov (United States)

    Wu, Fangfang; Zhou, Chunhui; Zhou, Dandan; Ou, Shiyi; Zhang, Xiaoai; Huang, Huihua

    2018-01-24

    A novel polysaccharide fraction (HEP-S) was extracted and isolated from the fruiting bodies of Hericium erinaceus. Structural characterization revealed that HEP-S had an average molecular weight of 1.83 × 10 4 Da and consisted of rhamnose, fucose, mannose, glucose and galactose at a molar ratio of 1.47 : 0.93 : 1.36 : 8.68 : 4.08. Periodate oxidation-Smith degradation and NMR analysis showed that the main linkage types of HEP-S were composed of (1→)-α-d-Glc, (1→3,4)-α-d-Glc, (1→6)-α-d-Gal, (1→3,4)-β-d-Man, (1→3,6)-α-Rha and (1→2)-β-l-Fuc. The immunomodulatory assay indicated that HEP-S could significantly enhance the pinocytic and phagocytic capacity and promote the secretion of nitric oxide and pro-inflammatory cytokines by activating the corresponding mRNA and protein expression in RAW 264.7 cells involving a toll-like receptor 2 membrane receptor. Besides, HEP-S was also found to improve the adaptive immune function by enhancing T and B lymphocyte proliferation and increasing the interleukin-2, interleukin-4 and interferon-γ secretion in spleen lymphocytes. These results suggested that HEP-S could be used as a potential immunoregulatory agent in functional foods.

  12. Characterization of Two Homogalacturonan Pectins with Immunomodulatory Activity from Green Tea

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    Huijun Wang

    2014-06-01

    Full Text Available Two natural homogalacturonan (HG pectins (MW ca. 20 kDa were isolated from green tea based on their immunomodulatory activity. The crude tea polysaccharides (TPS1 and TPS2 were obtained from green tea leaves by hot water extraction and followed by 40% and 70% ethanol precipitation, respectively. Two homogenous water soluble polysaccharides (TPS1-2a and TPS1-2b were obtained from TPS1 after purification with gel permeation, which gave a higher phagocytic effect than TPS2. A combination of composition, methylation and configuration analyses, as well as NMR (nuclear magnetic resonance spectroscopy revealed that TPS1-2a and TPS1-2b were homogalacturonan (HG pectins consisting of a backbone of 1,4-linked α-d-galacturonic acid (GalA residues with 28.4% and 26.1% of carboxyl groups as methyl ester, respectively. The immunological assay results demonstrated that TPS1-2, which consisted mainly of HG pectins, showed phagocytosis-enhancing activity in HL-60 cells.

  13. Simultaneous versus Sequential Intratympanic Steroid Treatment for Severe-to-Profound Sudden Sensorineural Hearing Loss.

    Science.gov (United States)

    Yoo, Myung Hoon; Lim, Won Sub; Park, Joo Hyun; Kwon, Joong Keun; Lee, Tae-Hoon; An, Yong-Hwi; Kim, Young-Jin; Kim, Jong Yang; Lim, Hyun Woo; Park, Hong Ju

    2016-01-01

    Severe-to-profound sudden sensorineural hearing loss (SSNHL) has a poor prognosis. We aimed to compare the efficacy of simultaneous and sequential oral and intratympanic steroids for this condition. Fifty patients with severe-to-profound SSNHL (>70 dB HL) were included from 7 centers. The simultaneous group (27 patients) received oral and intratympanic steroid injections for 2 weeks. The sequential group (23 patients) was treated with oral steroids for 2 weeks and intratympanic steroids for the subsequent 2 weeks. Pure-tone averages (PTA) and word discrimination scores (WDS) were compared before treatment and 2 weeks and 1 and 2 months after treatment. Treatment outcomes according to the modified American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria were also analyzed. The improvement in PTA and WDS at the 2-week follow-up was 23 ± 21 dB HL and 20 ± 39% in the simultaneous group and 31 ± 29 dB HL and 37 ± 42% in the sequential group; this was not statistically significant. Complete or partial recovery at the 2-week follow-up was observed in 26% of the simultaneous group and 30% of the sequential group; this was also not significant. The improvement in PTA and WDS at the 2-month follow-up was 40 ± 20 dB HL and 37 ± 35% in the simultaneous group and 41 ± 25 dB HL and 48 ± 41% in the sequential group; this was not statistically significant. Complete or partial recovery at the 2-month follow-up was observed in 33% of the simultaneous group and 35% of the sequential group; this was also not significant. Seven patients in the sequential group did not need intratympanic steroid injections for sufficient improvement after oral steroids alone. Simultaneous oral/intratympanic steroid treatment yielded a recovery similar to that produced by sequential treatment. Because the addition of intratympanic steroids can be decided upon based on the improvement after an oral steroid, the sequential regimen can be recommended to avoid unnecessary

  14. Immunomodulatory effects in a phase II study of lenalidomide combined with cetuximab in refractory KRAS-mutant metastatic colorectal cancer patients.

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    Anita K Gandhi

    Full Text Available This study assessed the immunomodulatory effects in previously treated KRAS-mutant metastatic colorectal cancer patients participating in a phase II multicenter, open-label clinical trial receiving lenalidomide alone or lenalidomide plus cetuximab. The main findings show the T cell immunostimulatory properties of lenalidomide as the drug induced a decrease in the percentage CD45RA(+ naïve T cells 3-fold while increasing the percentage HLA-DR(+ activated T helper cells and percentage total CD45RO(+ CD8(+ memory T cytotoxic cells, 2.6- and 2.1-fold respectively (p<0.0001. In addition, lenalidomide decreased the percentage of circulating CD19(+ B cells 2.6-fold (p<0.0001. Lenalidomide increased a modest, yet significant, 1.4-fold change in the percentage of circulating natural killer cells. Our findings indicate that lenalidomide significantly activates T cells, suggestive of an immunotherapeutic role for this drug in settings of maintenance therapy and tumor immunity. Furthermore, reported for the first time is the effect of lenalidomide in combination with cetuximab on T cell function, including increases in circulating naïve and central memory T cells. In summary, lenalidomide and cetuximab have significant effects on circulating immune cells in patients with colorectal carcinoma.ClinicalTrials.gov NCT01032291.

  15. Recombinant FIP-gat, a Fungal Immunomodulatory Protein from Ganoderma atrum, Induces Growth Inhibition and Cell Death in Breast Cancer Cells.

    Science.gov (United States)

    Xu, Hui; Kong, Ying-Yu; Chen, Xin; Guo, Meng-Yuan; Bai, Xiao-Hui; Lu, Yu-Jia; Li, Wei; Zhou, Xuan-Wei

    2016-04-06

    FIP-gat, an immunomodulatory protein isolated from Ganoderma atrum, is a new member of the FIP family. Little is known, however, about its expressional properties and antitumor activities. It was availably expressed in Escherichia coli with a total yield of 29.75 mg/L. The migration of recombinant FIP-gat (rFIP-gat) on SDS-PAGE corresponded to the predicted molecular mass, and the band was correctly detected by a specific antibody. To characterize the direct effects of rFIP-gat on MDA-MB-231 breast cancer cells, MDA-MB-231 cells were treated with different concentrations of rFIP-gat in vitro; the results showed that this protein could reduce cell viability dose-dependently with a median inhibitory concentration (IC50) of 9.96 μg/mL and agglutinate the MDA-MB-231 cells at a concentration as low as 5 μg/mL. Furthermore, FIP-gat at a concentration of 10 μg/mL can induce significant growth inhibition and cell death in MDA-MB-231 cells. Notably, FIP-gat treatment triggers significant cell cycle arrest at the G1/S transition and pronounced increase in apoptotic cell population. Molecular assays based on microarray and real-time PCR further revealed the potential mechanisms encompassing growth arrest, apoptosis, and autophagy underlying the phenotypic effects.

  16. Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

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    Hossein Rahavi

    2015-01-01

    Full Text Available Regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs might be applied for type 1 diabetes mellitus (T1DM treatment. Thus, we proposed in vitro assessment of adipose tissue-derived MSCs (AT-MSCs immunomodulation on autoimmune response along with beta cell protection in streptozotocin- (STZ- induced diabetic C57BL/6 mice model. MSCs were extracted from abdominal adipose tissue of normal mice and cultured to proliferate. Diabetic mice were prepared by administration of multiple low-doses of streptozotocin. Pancreatic islets were isolated from normal mice and splenocytes prepared from normal and diabetic mice. Proliferation, cytokine production, and insulin secretion assays were performed in coculture experiments. AT-MSCs inhibited splenocytes proliferative response to specific (islet lysate and nonspecific (PHA triggers in a dose-dependent manner (P<0.05. Decreased production of proinflammatory cytokines, such as IFN-γ, IL-2, and IL-17, and increased secretion of regulatory cytokines such as TGF-β, IL-4, IL-10, and IL-13 by stimulated splenocytes were also shown in response to islet lysate or PHA stimulants (P<0.05. Finally, we demonstrated that AT-MSCs could effectively sustain viability as well as insulin secretion potential of pancreatic islets in the presence of reactive splenocytes (P<0.05. In conclusion, it seems that MSCs may provide a new horizon for T1DM cell therapy and islet transplantation in the future.

  17. Targeting superoxide dismutase to endothelial caveolae profoundly alleviates inflammation caused by endotoxin.

    Science.gov (United States)

    Shuvaev, Vladimir V; Kiseleva, Raisa Yu; Arguiri, Evguenia; Villa, Carlos H; Muro, Silvia; Christofidou-Solomidou, Melpo; Stan, Radu V; Muzykantov, Vladimir R

    2018-02-28

    Inflammatory mediators binding to Toll-Like receptors (TLR) induce an influx of superoxide anion in the ensuing endosomes. In endothelial cells, endosomal surplus of superoxide causes pro-inflammatory activation and TLR4 agonists act preferentially via caveolae-derived endosomes. To test the hypothesis that SOD delivery to caveolae may specifically inhibit this pathological pathway, we conjugated SOD with antibodies (Ab/SOD, size ~10nm) to plasmalemmal vesicle-associated protein (Plvap) that is specifically localized to endothelial caveolae in vivo and compared its effects to non-caveolar target CD31/PECAM-1. Plvap Ab/SOD bound to endothelial cells in culture with much lower efficacy than CD31 Ab/SOD, yet blocked the effects of LPS signaling with higher efficiency than CD31 Ab/SOD. Disruption of cholesterol-rich membrane domains by filipin inhibits Plvap Ab/SOD endocytosis and LPS signaling, implicating the caveolae-dependent pathway(s) in both processes. Both Ab/SOD conjugates targeted to Plvap and CD31 accumulated in the lungs after IV injection in mice, but the former more profoundly inhibited LPS-induced pulmonary inflammation and elevation of plasma level of interferon-beta and -gamma and interleukin-27. Taken together, these results indicate that targeted delivery of SOD to specific cellular compartments may offer effective, mechanistically precise interception of pro-inflammatory signaling mediated by reactive oxygen species. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans.

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    Luc Biedermann

    Full Text Available BACKGROUND: The human intestinal microbiota is a crucial factor in the pathogenesis of various diseases, such as metabolic syndrome or inflammatory bowel disease (IBD. Yet, knowledge about the role of environmental factors such as smoking (which is known to influence theses aforementioned disease states on the complex microbial composition is sparse. We aimed to investigate the role of smoking cessation on intestinal microbial composition in 10 healthy smoking subjects undergoing controlled smoking cessation. METHODS: During the observational period of 9 weeks repetitive stool samples were collected. Based on abundance of 16S rRNA genes bacterial composition was analysed and compared to 10 control subjects (5 continuing smokers and 5 non-smokers by means of Terminal Restriction Fragment Length Polymorphism analysis and high-throughput sequencing. RESULTS: Profound shifts in the microbial composition after smoking cessation were observed with an increase of Firmicutes and Actinobacteria and a lower proportion of Bacteroidetes and Proteobacteria on the phylum level. In addition, after smoking cessation there was an increase in microbial diversity. CONCLUSIONS: These results indicate that smoking is an environmental factor modulating the composition of human gut microbiota. The observed changes after smoking cessation revealed to be similar to the previously reported differences in obese compared to lean humans and mice respectively, suggesting a potential pathogenetic link between weight gain and smoking cessation. In addition they give rise to a potential association of smoking status and the course of IBD.

  19. The management of children with Down syndrome and profound hearing loss.

    Science.gov (United States)

    Phelan, E; Pal, R; Henderson, L; Green, K M J; Bruce, I A

    2016-01-01

    Although, the association between Down syndrome (DS) and conductive hearing loss is well recognized, the fact that a small proportion of these children may have a severe to profound sensorineural hearing loss that could benefit from cochlear implantation (CI) is less well understood. The management of significant co-morbidities in children with DS can delay initial diagnosis of hearing impairment and assessment of suitability for CI can likewise be challenging, due to difficulties conditioning to behavioural hearing tests. We performed a retrospective case note review of three children with DS referred to the Manchester Cochlear Implant Programme. Three illustrative cases are described including CI in a 4 years old. Using conventional outcome measurement instruments, the outcome could be considered to be suboptimal with a Categories of Auditory Performance score of 4 at 6 months post-op and at last follow up. In part, this is likely to reflect the delay in implantation, but the role of cognitive impairment must be considered. The cases described emphasize the importance of comprehensive radiological and audiological assessment in children with DS being considered for CI. The influence of cognitive impairment upon outcome of CI must be taken into account, but should not be considered a contra-indication to implantation in children with DS. Benefit that might be considered limited when quantified using existing general outcome measurement instruments, may have a significant impact upon psychosocial development and quality of life in children with significant cognitive impairment, or other additional needs.

  20. Partial neuroprotection by nNOS inhibition during profound asphyxia in preterm fetal sheep.

    Science.gov (United States)

    Drury, Paul P; Davidson, Joanne O; van den Heuij, Lotte G; Tan, Sidhartha; Silverman, Richard B; Ji, Haitao; Blood, Arlin B; Fraser, Mhoyra; Bennet, Laura; Gunn, Alistair Jan

    2013-12-01

    Preterm brain injury is partly associated with hypoxia-ischemia starting before birth. Excessive nitric oxide production during HI may cause nitrosative stress, leading to cell membrane and mitochondrial damage. We therefore tested the hypothesis that therapy with a new, selective neuronal nitric oxide synthase (nNOS) inhibitor, JI-10 (0.022mg/kg bolus, n=8), given 30min before 25min of complete umbilical cord occlusion was protective in preterm fetal sheep at 101-104day gestation (term is 147days), compared to saline (n=8). JI-10 had no effect on fetal blood pressure, heart rate, carotid and femoral blood flow, total EEG power, nuchal activity, temperature or intracerebral oxygenation on near-infrared spectroscopy during or after occlusion. JI-10 was associated with later onset of post-asphyxial seizures compared with saline (p<0.05), and attenuation of the subsequent progressive loss of cytochrome oxidase (p<0.05). After 7days recovery, JI-10 was associated with improved neuronal survival in the caudate nucleus (p<0.05), but not the putamen or hippocampus, and more CNPase positive oligodendrocytes in the periventricular white matter (p<0.05). In conclusion, prophylactic nNOS inhibition before profound asphyxia was associated with delayed onset of seizures, slower decline of cytochrome oxidase and partial white and gray matter protection, consistent with protection of mitochondrial function. © 2013.

  1. Attentional processes in interactions between people with profound intellectual and multiple disabilities and direct support staff.

    Science.gov (United States)

    Hostyn, Ine; Ine, Hostyn; Neerinckx, Heleen; Heleen, Neerinckx; Maes, Bea; Bea, Maes

    2011-01-01

    Few studies have examined joint attention in interactions with persons with profound intellectual and multiple disabilities (PIMD), despite its important role in high-quality interaction. The purpose of this study is to describe the attention-directing behaviours of persons with PIMD and their direct support staff and the attention episodes resulting from their interactions, and to understand how these variables relate to each other. Video observations of 17 staff-client dyads were coded using partial interval recording. The results showed considerable variation across individuals and dyads. In general, persons with PIMD directed the attention of staff members infrequently. The staff members frequently directed their clients' attention towards a topic of interest but did not often use the tactile modality. Within the staff-client dyad, there was not much joint attention; however, shared attention episodes occurred frequently. Shared attention and joint attention are strongly correlated. A negative correlation was found between clients not using attention-directing behaviours and staff members using tactile methods to direct the attention, and joint attention episodes. This study presents both directions for future research and practical implications. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. The current status of audiologic rehabilitation for profound unilateral sensorineural hearing loss.

    Science.gov (United States)

    Bishop, Charles E; Eby, Thomas L

    2010-03-01

    Audiologic rehabilitation of individuals with profound unilateral sensorineural hearing loss (USNHL) has traditionally been limited to the use of air-conduction contralateral routing of sound (CROS) hearing aids. Treatment for these individuals has expanded with new applications of the bone-anchored hearing aid (BAHA), transcranial hearing aid (t-CROS), and the cochlear implant. In this article, the authors review the literature that addresses these various treatment options. Contemporary review Historical information is available that describes the limited efficacy of air-conduction CROS hearing aids in lifting hearing handicap associated with USNHL. Current investigations on providing cross hearing are generally focused on use of the BAHA. Little is known at present whether new developments in hearing aid technology can improve on conventional air-conduction CROS or t-CROS approaches. Interestingly, the cochlear implant seems to be a viable option for individuals with USNHL and tinnitus who also have intact auditory nerve pathways. There is indication in the literature that BAHA provides greater relief of hearing handicap associated with USNHL than CROS hearing aids; however, both have been found to provide limited patient satisfaction and seemingly fall short of restoring true sound localization. Adequate trials have not been performed comparing BAHA with the best CROS hearing aid technology. Transcranial hearing aids and cochlear implants are experimental methods to treat USNHL and hold promise, although there remains a lack of studies available to fully support this.

  3. Differentiating characteristics of deafblindness and autism in people with congenital deafblindness and profound intellectual disability.

    Science.gov (United States)

    Hoevenaars-van den Boom, M A A; Antonissen, A C F M; Knoors, H; Vervloed, M P J

    2009-06-01

    In persons with deafblindness, it is hard to distinguish autism spectrum disorders from several deafblind specific behaviours caused by the dual sensory impairments, especially when these persons are also intellectually disabled. As a result, there is an over-diagnosis of autism in persons who are deafblind leading to unsuitable interventions. Autism as specified by the DSM-IV was studied in 10 persons with congenital deafblindness with profound intellectual disabilities. Behaviours of people with deafblindness and autism (n = 5) and of people with deafblindness without autism (n = 5) were observed in a semi-standardised assessment. All people with deafblindness showed impairments in social interaction, communication and language. In contrast to persons without autism, people with deafblindness and autism showed significantly more impairments in reciprocity of social interaction, quality of initiatives to contact and the use of adequate communicative signals and functions. No differences between the groups were found for quantity and persistence of stereotyped behaviour, quality of play and exploration and adequate problem-solving strategies. This study indicates that there are some possibilities to differentiate autism from behaviours specific for deafblindness. It also confirms the large overlap in overt behaviours between people with deafblindness and persons with autism.

  4. A Glance on Diagnosis and Ttreatment of Profound Fatigue in Multiple Sclerosis

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    Mojtaba Azimian

    2007-09-01

    Full Text Available Multiple Sclerosis (M.S is one of the prevalent diseases of the central nervous system which cause disability in young adults. This appears as neural signs in different parts and various times. The main defect is local deterioration or destruction of myelin tissue in the brain and spinal cord. Profound fatigue is one the most common symptoms of this disease. Because MS is prevalent in middle ages, so the presence of this symptom affects the life and activity of the patient In these ages people have high amount of activities and this functional disorder creates many difficulties for daily works in patient. For this reason, fatigue problem in patients, always, have caught the attention of researchers. Despite numerous studies, still the exact reason for producing fatigue have not been mentioned But several mechanisms have been discussed, such as: autoimmune mechanism of the disease, Involvement and disorder of endocrine system, involvement of central nervous system and de-synchronization of autonom system. Among these, autoimmune mechanism is considered as a main role in producing fatigue. Lack of proper knowledge regarding exact fatigue mechanism several problems in its treatment. Evaluation is the first step for controlling fatigue, which is done through various tests. Clear and proper evaluation can be obtained by these tests. After evaluation, non-drug and finally drug procedures are helpful. In non-drug treatment the focus is on: sport exercises, suitable diet program, identification and improvement of the patient psychotic disorders, energy conservation methods. Finally, the use of drugs such as Amantadine, Pemoline and Modafini is recommended for fatigue treatment.

  5. Profound tumor-specific Th2 bias in patients with malignant glioma

    International Nuclear Information System (INIS)

    Shimato, Shinji; Maier, Lisa M; Maier, Richard; Bruce, Jeffrey N; Anderson, Richard CE; Anderson, David E

    2012-01-01

    Vaccination against tumor-associated antigens is one promising approach to immunotherapy against malignant gliomas. While previous vaccine efforts have focused exclusively on HLA class I-restricted peptides, class II-restricted peptides are necessary to induce CD4 + helper T cells and sustain effective anti-tumor immunity. In this report we investigated the ability of five candidate peptide epitopes derived from glioma-associated antigens MAGE and IL-13 receptor α2 to detect and characterize CD4 + helper T cell responses in the peripheral blood of patients with malignant gliomas. Primary T cell responses were determined by stimulating freshly isolated PBMCs from patients with primary glioblastoma (GBM) (n = 8), recurrent GBM (n = 5), meningioma (n = 7), and healthy controls (n = 6) with each candidate peptide, as well as anti-CD3 monoclonal antibody (mAb) and an immunodominant peptide epitope derived from myelin basic protein (MBP) serving as positive and negative controls, respectively. ELISA was used to measure IFN-γ and IL-5 levels, and the ratio of IFN-γ/IL-5 was used to determine whether the response had a predominant Th1 or Th2 bias. We demonstrate that novel HLA Class-II restricted MAGE-A3 and IL-13Rα2 peptides can detect T cell responses in patients with GBMs as well as in healthy subjects. Stimulation with a variety of peptide antigens over-expressed by gliomas is associated with a profound reduction in the IFN-γ/IL-5 ratio in GBM patients relative to healthy subjects. This bias is more pronounced in patients with recurrent GBMs. Therapeutic vaccine strategies to shift tumor antigen-specific T cell response to a more immunostimulatory Th1 bias may be needed for immunotherapeutic trials to be more successful clinically

  6. Cochlear implantation: is hearing preservation necessary in severe to profound hearing loss?

    Science.gov (United States)

    Derinsu, Ufuk; Serin, Gediz Murat; Akdaş, Ferda; Batman, Çağlar

    2011-03-01

    The goal of the cochlear implant surgery is to place the electrode array with minimal damage to preserve the residual hearing. Round-window insertion can be performed in a manner that is potentially less traumatic than the standard cochleostomy. The purpose of the study was to investigate audiological results of the round-window approach using standard electrode. A retrospective study was performed to evaluate our experience in patients with implanted through round window between January 2007 and March 2009. Sixty patients had undergone cochlear implant surgery through the round window with full insertion of a standard electrode array. Preoperative and postoperative pure-tone thresholds were measured for implanted ears in the range of 250 to 4000 Hz. Within these 60 cases, 31 patients had been evaluated. The population comprised 16 women and 15 men. The mean age was 15.96 years (range, 4-64 years). Follow-up times ranged from 6 to 26 months. Preservation of low-frequency hearing (250 and 500 Hz) was achieved in 27 (87%) of 31 patients. Complete hearing preservation (all frequencies) was accomplished in 11 patients (35.48%). No hearing could be determined postoperatively in 4 patients (12.9%), having preoperative thresholds of 120 dB at 250, 500, and 1000 Hz. Round-window approach has been widely used for preservation of residual hearing. In our patients with severe to profound hearing loss, we preserved residual hearing. Although the residual hearing cannot be sufficient for using additional acoustic stimulation, the preserved residual hearing means minimal damage and a more convenient cochlea, so this is promising for future development.

  7. Recurrent Vestibular Migraine Vertigo Attacks Associated With the Development of Profound Bilateral Vestibulopathy: A Case Series.

    Science.gov (United States)

    Wester, Jacob L; Ishiyama, Akira; Ishiyama, Gail

    2017-09-01

    Bilateral vestibulopathy (BVP) is a debilitating condition characterized by gait ataxia, oscillopsia, and imbalance. Case series of patients with migraine-linked vertigo spells and profound BVP. PATIENT 1:: A 69-year-old man presented with a history of recurrent severe vertigo spells lasting up to 3 days in duration associated with prostrating migraine headaches starting at age 60. His symptoms were misdiagnosed as an anxiety syndrome. At age 68, electronystagmography (ENG) revealed bilaterally absent caloric responses and complete BVP. His hearing was normal. PATIENT 2:: A 51-year-old man presented with a history of "earthquake-like" vertigo, sharp head pain, and phonophobia. These episodes occurred a handful of times over a 7-year period. Previous ENG testing at age 43 was normal. However, his ENG at age 48 revealed complete BVP. He was started on acetazolamide and noted improved balance, although subsequent ENG was unchanged. PATIENT 3:: A 49-year-old woman presented with a history of recurrent migraines with visual aura associated with vertigo lasting 1 hour. ENG at age 50 revealed complete BVP. Subjectively, she noted improved balance with acetazolamide and subsequent ENG demonstrated mild improvement. PATIENT 4:: A 43-year-old man presented with a 5-year history of optical migraines and recurrent vertigo spells, lasting 30 seconds, which was misdiagnosed as positional vertigo. He additionally had a 10-year history of oscillopsia. ENG at age 61 revealed complete BVP. In these cases, vestibular migraine was linked to recurrent vertigo spells that eventually led to complete bilateral vestibulopathy.

  8. RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice.

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    Enric Mocholí

    Full Text Available Rnd proteins are a subfamily of Rho GTPases involved in the control of actin cytoskeleton dynamics and other cell functions such as motility, proliferation and survival. Unlike other members of the Rho family, Rnd proteins lack GTPase activity and therefore remain constitutively active. We have recently described that RhoE/Rnd3 is expressed in the Central Nervous System and that it has a role in promoting neurite formation. Despite their possible relevance during development, the role of Rnd proteins in vivo is not known. To get insight into the in vivo function of RhoE we have generated mice lacking RhoE expression by an exon trapping cassette. RhoE null mice (RhoE gt/gt are smaller at birth, display growth retardation and early postnatal death since only half of RhoE gt/gt mice survive beyond postnatal day (PD 15 and 100% are dead by PD 29. RhoE gt/gt mice show an abnormal body position with profound motor impairment and impaired performance in most neurobehavioral tests. Null mutant mice are hypoactive, show an immature locomotor pattern and display a significant delay in the appearance of the hindlimb mature responses. Moreover, they perform worse than the control littermates in the wire suspension, vertical climbing and clinging, righting reflex and negative geotaxis tests. Also, RhoE ablation results in a delay of neuromuscular maturation and in a reduction in the number of spinal motor neurons. Finally, RhoE gt/gt mice lack the common peroneal nerve and, consequently, show a complete atrophy of the target muscles. This is the first model to study the in vivo functions of a member of the Rnd subfamily of proteins, revealing the important role of Rnd3/RhoE in the normal development and suggesting the possible involvement of this protein in neurological disorders.

  9. The notochord in Atlantic salmon (Salmo salar L.) undergoes profound morphological and mechanical changes during development.

    Science.gov (United States)

    Kryvi, Harald; Rusten, Iselin; Fjelldal, Per Gunnar; Nordvik, Kari; Totland, Geir K; Karlsen, Tine; Wiig, Helge; Long, John H

    2017-11-01

    We present the development of the notochord of the Atlantic salmon (Salmo salar L.), from early embryo to sexually mature fish. Over the salmon's lifespan, profound morphological changes occur. Cells and gross structures of the notochord reorganize twice. In the embryo, the volume of the notochord is dominated by large, vacuolated chordocytes; each cell can be modeled as a hydrostat organized into a larger cellular-hydrostat network, structurally bound together with desmosomes. After the embryo hatches and grows into a fry, vacuolated chordocytes disappear, replaced by extracellular lacunae. The formation of mineralized, segmental chordacentra stiffens the notochord and creates intervertebral joints, where tissue strain during lateral bending is now focused. As development proceeds towards the parr stage, a process of devacuolization and intracellular filament accumulation occur, forming highly dense, non-vacuolated chordocytes. As extracellular lacunae enlarge, they are enclosed by dense filamentous chordocytes that form transverse intervertebral septa, which are connected to the intervertebral ligaments, and a longitudinal notochordal strand. In the vertebral column of pelagic adults, large vacuolated chordocytes reappear; cells of this secondary population have a volume up to 19 000 times larger than the primary vacuolated chordocytes of the early notochord. In adults the lacunae have diminished in relative size. Hydrostatic pressure within the notochord increases significantly during growth, from 525 Pa in the alevins to 11 500 Pa in adults, at a rate of increase with total body length greater than that expected by static stress similarity. Pressure and morphometric measurements were combined to estimate the stress in the extracellular material of the notochordal sheath and intervertebral ligaments and the flexural stiffness of the axial skeleton. The functional significance of the morphological changes in the axial skeleton is discussed in relation to the

  10. NATURE FACILITATES CONNECTION WITH THE PROFOUND SELF: NEEDS, GOALS AND RESOURCE AWARENESS

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    Nicoleta Răban-Motounu

    2014-11-01

    Full Text Available The present study is based on Kaplan and Kaplan’s (1989 theory explaining the restorative effects that nature has on a person’s psychic. According to this theory, nature exerts a “soft fascination” combining the activation of involuntary attention mechanisms with the reflexive awareness, allowing a spontaneous detachment from stress factors and automatic functioning, and also the feeling of compatibility between personal purposes, and the possibilities for action offered by the environment (a sense of meaning. Our objective was to investigate the effects of nature on Self awareness: the immediate, emotional experience; needs awareness and organization; plans for action, and availability of resources, both personal, and external. We conducted an experiment with an experimental group (persons watching a video with life in nature and an active control group (involved in a psychotherapeutic technique focused on confronting and solving personal difficulties by creative means, accompanied by a short psychological analysis. The effects were assessed in terms of “here and now” emotions and available resources according to a self-evaluation scale, and with open-ended questions regarding personal needs and goals. The results showed that, for the experimental group, the relaxation effects and the awareness of long term goals were stronger, while all the other effects were the same as for the control group. The results suggest that indeed, nature helps a person get in contact with her profound Self, allowing the access to both “here and now” basic needs, and also long term goals (inner sources of meaning, the sense of connection between internal tendencies, personal, and external resources, resulting in increased positive emotions, and decreased negative emotions. Nature contemplation may facilitate a meditative state whit all its positive effects.

  11. Classic Bartter syndrome complicated with profound growth hormone deficiency: a case report.

    Science.gov (United States)

    Adachi, Masanori; Tajima, Toshihiro; Muroya, Koji; Asakura, Yumi

    2013-12-30

    Classic Bartter syndrome is a salt-wasting tubulopathy caused by mutations in the CLCNKB (chloride channel Kb) gene. Although growth hormone deficiency has been suggested as a cause for persistent growth failure in patients with classic Bartter syndrome, in our opinion the diagnoses of growth hormone deficiency has been unconvincing in some reports. Moreover, Gitelman syndrome seems to have been confused with Bartter syndrome in some cases in the literature. In the present work, we describe a new case with CLCNKB gene mutations and review the reported cases of classic Bartter syndrome associated with growth hormone deficiency. Our patient was a Japanese boy diagnosed as having classic Bartter syndrome at eight months of age. The diagnosis of Bartter syndrome was confirmed by CLCNKB gene analysis, which revealed compound heterozygous mutations with deletion of exons 1 to 3 (derived from his mother) and ΔL130 (derived from his father). His medical therapy consisted of potassium (K), sodium chloride, spironolactone, and anti-inflammatory agents; this regime was started at eight months of age. Our patient was very short (131.1cm, -4.9 standard deviation) at 14.3 years and showed profoundly impaired growth hormone responses to pharmacological stimulants: 0.15μg/L to insulin-induced hypoglycemia and 0.39μg/L to arginine. His growth response to growth hormone therapy was excellent. The present case strengthens the association between classic Bartter syndrome and growth hormone deficiency. We propose that growth hormone status should be considered while treating children with classic Bartter syndrome.

  12. Achieving and sustaining profound institutional change in healthcare: case study using neo-institutional theory.

    Science.gov (United States)

    Macfarlane, Fraser; Barton-Sweeney, Cathy; Woodard, Fran; Greenhalgh, Trisha

    2013-03-01

    Change efforts in healthcare sometimes have an ambitious, whole-system remit and seek to achieve fundamental changes in norms and organisational culture rather than (or as well as) restructuring the service. Long-term evaluation of such initiatives is rarely undertaken. We report a secondary analysis of data from an evaluation of a profound institutional change effort in London, England, using a mixed-method longitudinal case study design. The service had received £15 million modernisation funding in 2004, covering multiple organisations and sectors and overseen by a bespoke management and governance infrastructure that was dismantled in 2008. In 2010-11, we gathered data (activity statistics, documents, interviews, questionnaires, site visits) and compared these with data from 2003 to 2008. Data analysis was informed by neo-institutional theory, which considers organisational change as resulting from the material-resource environment and three 'institutional pillars' (regulative, normative and cultural-cognitive), enacted and reproduced via the identities, values and activities of human actors. Explaining the long-term fortunes of the different components of the original programme and their continuing adaptation to a changing context required attention to all three of Scott's pillars and to the interplay between macro institutional structures and embedded human agency. The paper illustrates how neo-institutional theory (which is typically used by academics to theorise macro-level changes in institutional structures over time) can also be applied at a more meso level to inform an empirical analysis of how healthcare organisations achieve change and what helps or hinders efforts to sustain those changes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. What parents find important in the support of a child with profound intellectual and multiple disabilities.

    Science.gov (United States)

    Jansen, S L G; van der Putten, A A J; Vlaskamp, C

    2013-05-01

    The importance of a partnership between parents and professionals in the support of children with disabilities is widely acknowledged and is one of the key elements of 'family-centred care'. To what extent family-centred principles are also applied to the support of persons with profound intellectual and multiple disabilities (PIMD) is not yet known. The purpose of this exploratory study was to examine what parents with a child with PIMD find important in the support of their child. In addition, we examined which child or parent characteristics influence these parental opinions. In total, 100 parents completed an adapted version of the Measure of Processes of Care. Mean unweighted and weighted scale scores were computed. Non-parametric tests were used to examine differences in ratings due to child (gender, age, type and number of additional disabilities, type of services used and duration of service use) and parent characteristics (gender, involvement with support and educational level). Parents rated situations related to 'Respectful and Supportive Care' and 'Enabling and Partnership' with averages of 7.07 and 6.87 respectively on a scale from 1 to 10. They were generally satisfied with the services provided, expressed in a mean score of 6.88 overall. The age of the child significantly affected the scores for 'Providing Specific Information about the Child'. Parents of children in the '6-12 years' age group gave significantly higher scores on this scale than did parents of children in the '≥17 years' age group (U = 288, r = -0.34). This study shows that parents with children with PIMD find family-centred principles in the professional support of their children important. Although the majority of parents are satisfied with the support provided for their children, a substantial minority of the parents indicated that they did not receive the support they find important. © 2012 Blackwell Publishing Ltd.

  14. Time use of parents raising children with severe or profound intellectual and multiple disabilities.

    Science.gov (United States)

    Luijkx, J; van der Putten, A A J; Vlaskamp, C

    2017-07-01

    Raising children with severe or profound intellectual and multiple disabilities (PIMD) is expected to put extreme pressure on parental time use patterns. The aim of this study was to examine the total time use of mothers and fathers raising children with PIMD and compare it with the time use of parents of typically developing children. Twenty-seven fathers and 30 mothers raising children with PIMD completed a time use diary on a mobile phone or tablet app, as did 66 fathers and 109 mothers of typically developing children. Independent t-tests and Mann-Whitney tests were performed to compare mean time use. There are no differences in the time use of parents of children with PIMD on contracted time (paid work and educational activities) and necessary time (personal care, eating and drinking and sleeping) when compared with parents of typically developing children. There are significant differences between the parents of children with PIMD and the parents of typically developing children in terms of committed time (time for domestic work and the care and supervision of their children) and free time. The mothers of children with PIMD spend significantly less time on domestic work and more time on care and supervision than mothers of typically developing children. This study shows that the parents of children with PIMD have to spend a significant amount of time on care tasks and have on average 1.5 h less free time per day than parents of typically developing children. This is a striking difference, because leisure time can substantially contribute to well-being. Therefore, it is important not only to consider a child with PIMD's support needs but also to identify what parents need to continue their children's daily care and supervision. © 2017 John Wiley & Sons Ltd.

  15. Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response

    Science.gov (United States)

    Wang, Wei; Wang, Jing; Dong, Sheng-fu; Liu, Chun-hong; Italiani, Paola; Sun, Shu-hui; Xu, Jing; Boraschi, Diana; Ma, Shi-ping; Qu, Di

    2010-01-01

    Aim: To investigate the immunomodulatory effects of andrographolide on both innate and adaptive immune responses. Methods: Andrographolide (10 μg/mL in vitro or 1 mg/kg in vivo) was used to modulate LPS-induced classical activated (M1) or IL-4-induced alternative activated (M2) macrophages in vitro and humor immune response to HBsAg in vivo. Cytokine gene expression profile (M1 vs M2) was measured by real-time PCR, IL-12/IL-10 level was detected by ELISA, and surface antigen expression was evaluated by flow cytometry, whereas phosphorylation level of ERK 1/2 and AKT was determined by Western blot. The level of anti-HBs antibodies in HBsAg immunized mice was detected by ELISA, and the number of HBsAg specific IL-4-producing splenocyte was enumerated by ELISPOT. Results: Andrographolide treatment in vitro attenuated either LPS or IL-4 induced macrophage activation, inhibited both M1 and M2 cytokines expression and decreased IL-12/IL-10 ratio (the ratio of M1/M2 polarization). Andrographolide down-regulated the expression of mannose receptor (CD206) in IL-4 induced macrophages and major histocompability complex/costimulatory molecules (MHC I, CD40, CD80, CD86) in LPS-induced macrophages. Correspondingly, anti-HBs antibody production and the number of IL-4-producing splenocytes were reduced by in vivo administration of andrographolide. Reduced phosphorylation levels of ERK1/2 and AKT were observed in macrophages treated with andrographolide. Conclusion: Andrographolide can modulate the innate and adaptive immune responses by regulating macrophage phenotypic polarization and Ag-specific antibody production. MAPK and PI3K signaling pathways may participate in the mechanisms of andrographolide regulating macrophage activation and polarization. PMID:20139902

  16. Distinct Immunomodulatory Effects of Spermine Oxidase in Colitis Induced by Epithelial Injury or Infection

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    Alain P. Gobert

    2018-06-01

    Full Text Available Polyamines have been implicated in numerous biological processes, including inflammation and carcinogenesis. Homeostatic regulation leads to interconversion of the polyamines putrescine and the downstream metabolites spermidine and spermine. The enzyme spermine oxidase (SMOX, which back-converts spermine to spermidine, contributes to regulation of polyamine levels, but can also have other effects. We have implicated SMOX in gastric inflammation and carcinogenesis due to infection by the pathogen Helicobacter pylori. In addition, we reported that SMOX can be upregulated in humans with inflammatory bowel disease. Herein, we utilized Smox-deficient mice to examine the role of SMOX in two murine colitis models, Citrobacter rodentium infection and dextran sulfate sodium (DSS-induced epithelial injury. In C. rodentium-infected wild-type (WT mice, there were marked increases in colon weight/length and histologic injury, with mucosal hyperplasia and inflammatory cell infiltration; these changes were ameliorated in Smox−/− mice. In contrast, with DSS, Smox−/− mice exhibited substantial mortality, and increased body weight loss, colon weight/length, and histologic damage. In C. rodentium-infected WT mice, there were increased colonic levels of the chemokines CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10, and the cytokines IL-6, TNF-α, CSF3, IFN-γ, and IL-17; each were downregulated in Smox−/− mice. In DSS colitis, increased levels of IL-6, CSF3, and IL-17 were further increased in Smox−/− mice. In both models, putrescine and spermidine were increased in WT mice; in Smox−/− mice, the main effect was decreased spermidine and spermidine/spermine ratio. With C. rodentium, polyamine levels correlated with histologic injury, while with DSS, spermidine was inversely correlated with injury. Our studies indicate that SMOX has immunomodulatory effects in experimental colitis via polyamine flux. Thus, SMOX contributes to the immunopathogenesis of

  17. Immunomodulatory Effects of a Bioactive Compound Isolated from Dryopteris crassirhizoma on the Grass Carp Ctenopharyngodon idella

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    Cheng Chi

    2016-01-01

    Full Text Available In the present study, we investigated effects of compound kaempferol 3-a-L-(4-O-acetylrhamnopyranoside-7-a-L-rhamnopyranoside (SA isolated from Dryopteris crassirhizoma during immune-related gene expression in Ctenopharyngodon idella head kidney macrophages (CIHKM. The expression of immune-related genes (IL-1β, TNF-α, MyD88, and Mx1 were investigated using real-time PCR at 2 h, 8 h, 12 h, and 24 h after incubation with 1, 10, and 50 μg mL−1 of SA. Furthermore, fish were injected intraperitoneally with 100 μL of SA, and immune parameters such as lysozyme activity, complement C3, SOD, phagocytic activity, and IgM level were examined at 1, 2, and 3 weeks after injection. The differential expression of cytokines was observed after exposure to SA. IL-1β genes displayed significant expression at 2 and 8 h after exposure to 1–10 μg mL−1 of SA. SA also induced gene expression of cytokines such as MyD88, Mx1, and TNF-α. Furthermore, enhanced immune parameters in grass carp confirmed the immunomodulatory activity of SA. Interestingly, this compound has no toxic effect on CIHKM cells as tested by MTT assay. In addition, fish immunised with 10 μg mL−1 of SA exhibited maximum resistance against Aeromonas hydrophila infection. These results suggest that SA has the potential to stimulate immune responses in grass carp.

  18. Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia.

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    Urvashi Bhan

    Full Text Available Post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60% when bacterial infections are secondary to multi-drug resistant (MDR pathogens. Staphylococcus aureus, in particular community acquired MRSA (cMRSA, has emerged as a leading cause of post influenza pneumonia.Linezolid (LZD prevents acute lung injury in murine model of post influenza bacterial pneumonia.Mice were infected with HINI strain of influenza and then challenged with cMRSA at day 7, treated with antibiotics (LZD or Vanco or vehicle 6 hours post bacterial challenge and lungs and bronchoalveolar lavage fluid (BAL harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokine analysis and assessment of lung injury.Mice treated with LZD or Vanco had lower bacterial burden in the lung and no systemic dissemination, as compared to the control (no antibiotic group at 24 hours post bacterial challenge. As compared to animals receiving Vanco, LZD group had significantly lower numbers of neutrophils in the BAL (9×10(3 vs. 2.3×10(4, p < 0.01, which was associated with reduced levels of chemotactic chemokines and inflammatory cytokines KC, MIP-2, IFN-γ, TNF-α and IL-1β in the BAL. Interestingly, LZD treatment also protected mice from lung injury, as assessed by albumin concentration in the BAL post treatment with H1N1 and cMRSA when compared to vanco treatment. Moreover, treatment with LZD was associated with significantly lower levels of PVL toxin in lungs.Linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cMRSA pneumonia.

  19. Structure and Antitumor and Immunomodulatory Activities of a Water-Soluble Polysaccharide from Dimocarpus longan Pulp

    Science.gov (United States)

    Meng, Fa-Yan; Ning, Yuan-Ling; Qi, Jia; He, Zhou; Jie, Jiang; Lin, Juan-Juan; Huang, Yan-Jun; Li, Fu-Sen; Li, Xue-Hua

    2014-01-01

    A new water-soluble polysaccharide (longan polysaccharide 1 (LP1)) was extracted and successfully purified from Dimocarpus longan pulp via diethylaminoethyl (DEAE)-cellulose anion-exchange and Sephacryl S-300 HR gel chromatography. The chemical structure was determined using Infrared (IR), gas chromatography (GC) and nuclear magnetic resonance (NMR) analysis. The results indicated that the molecular weight of the sample was 1.1 × 105 Da. Monosaccharide composition analysis revealed that LP1 was composed of Glc, GalA, Ara and Gal in a molar ratio of 5.39:1.04:0.74:0.21. Structural analysis indicated that LP1 consisted of a backbone of →4)-α-d-Glcp-(1→4)-α-d-GalpA-(1→4)-α-d-Glcp-(1→4)-β-d-Glcp-(1→ units with poly saccharide side chains composed of →2)-β-d-Fruf-(1→2)-l-sorbose-(1→ attached to the O-6 position of the α-d-Glcp residues. In vitro experiments indicated that LP1 had significantly high antitumor activity against SKOV3 and HO8910 tumor cells, with inhibition percentages of 40% and 50%, respectively. In addition, LP1 significantly stimulated the production of the cytokine interferon-γ (IFN-γ), increased the activity of murine macrophages and enhanced B- and T-lymphocyte proliferation. The results of this study demonstrate that LP1 has potential applications as a natural antitumor agent with immunomodulatory activity. PMID:24663085

  20. Immunomodulatory efficacy of ethanol extract of propolis on tumor-bearing mice with disseminated candidiasis.

    Science.gov (United States)

    Khosravi, A R; Shokri, H; Darvishi, S; Taghavi, M

    2014-12-01

    This study was aimed at investigating the effect of propolis on immunosurveillance by measuring the levels of serum interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in tumor-bearing mice with disseminated candidiasis. The ethanol extract of propolis was selected for this study. Balb/C female mice were infected with Candida albicans (C. albicans) and inoculated with spontaneous mouse mammary tumor (SMMT). The serum levels of tissue inhibitor of metalloproteinase-1(TIMP-1) were assessed by enzyme- linked immunosorbent assay (ELISA). Mice were treated daily with propolis solution (100mg/kg, 0.1 mL, orally) for 3 days before IV challenge with C. albicans and SC challenge with SMMT and continued for 10 days. The rates of survival and tumor growth of understudy mice were investigated as well. The levels of TNF-α, IFN-γ, IL-4, IL-10 and IL-17 cytokines in culture supernatants were determined by ELISA. The mean tumor size was significantly increased in tumor-bearing mice infected with C. albicans (16.98 ± 0.49 mm(2)) as compared to other mice groups (P<0.05). The results showed a significant decline of IL-4 and IL-10 levels after propolis administration to tumor-bearing mice infected with C. albicans (53.41 pg/mL, 156.81 pg/mL and 63.45 pg/mL) (P < 0.05). The increment of TNF-α (433.85 pg/mL) and IFN-γ (120.43 pg/mL) levels were also observed. Data revealed that propolis has remarkable immunomodulatory effect, which provides a scientific validation for the popular use of this natural substance, and further investigation will help to understand propolis usefulness during immunosuppressive conditions. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Immunomodulatory and antioxidant protective effect of Sarcocornia perennis L. (swampfire) in lead intoxicated rat.

    Science.gov (United States)

    Gargouri, Manel; Hamed, Houda; Akrouti, Amel; Christian, Magné; Ksouri, Riadh; El Feki, Abdelfattah

    2017-11-01

    Lead (Pb) is a very toxic metal present in the environment, causing disturbances of several functions. Preventive or curative effects of halophytic plants against these disorders may be a promising and safe therapeutic strategy. Thus, this study was designed to evaluate in vivo immunomodulatory and antioxidant effects of Sarcocornia perennis extract (Sp) against lead toxicity in rats. Groups of six animals each were treated with plant extract (via food), 6 g/L lead acetate (via drinking water) or a combination of both. At the end of the three-week period, rat exposure to lead caused reduction of liver weight but an increase of that of kidney. Moreover, lead intoxication-induced oxidative stress manifested by significant increases of inflammatory cytokines (except IL-10) and lipid peroxidation (TBARS), compared with the control group. Meanwhile, interleukin-10 (IL-10) and glutathione levels (GSH), as well as antioxidant activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were decreased. Considering liver and renal markers, lead treatment induced a significant increase in the activities of aminotransferases (AST, ALT), and in the levels of urea, creatinine and phosphorous, whereas total plasma protein, albumin and calcium levels were significantly decreased. S. perennis extract alone did not induce any significant changes in hepatic or renal markers, whereas the antioxidant markers were significantly increased. S. perennis supplementation significantly reduced the lead-induced elevation of serum IL-1ß, IL-6, TNF-α, IFN-γ and TBARS but increased the IL-10 and antioxidant enzyme activities. Overall, plant components ameliorated hepatorenal damages caused by lead.

  2. Antitumor and Immunomodulatory Effects of Polysaccharides from Broken-Spore of Ganoderma lucidum

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    Peng-Yun eWang

    2012-07-01

    Full Text Available The antitumor activity of Gl-BSP, a polysaccharide isolated from boiling water extract of the broken-spores of Ganoderma lucidum (Leyss ex Fr Karst. and its possible mechanism were investigated in vivo and in vitro. It was showed that Gl-BSP (50, 100, 200 mg/kg exhibited antitumor effect against Sarcoma 180 (S180 in BALB/c mice. The Gl-BSP was not cytotoxicity in S180 cells and PG cells (human lung carcinoma cell in vitro. However, Gl-BSP-treated serum potently inhibited S180 cells and PG cells proliferation in vitro. Moreover, Gl-BSP could promote the splenic lymphocyte proliferation induced by Con A or LPS, enhance nature killer cell (NK cell cytotoxic activity, augment the percentage of neutral red (NR phagocytosis by macrophages, and increase the percentage of the CD4+ or CD8+ subset in S180-bearing BALB/c mice. The level of IFN-γ, TNF-α and NO of serum apparently was increased by Gl-BSP. Gl-BSP also showed immunomodulatory activities in tumor-bearing mice. Furthermore,It was proved that neutralization with anti-TNF-α and/or anti-IFN-γ significantly diminished growth inhibition induced by Gl-BSP –treated serum in S180 or PG cells. Blocking effect was noted in the combination of anti-TNF-α and anti-IFN-γ. These observations suggest that the antitumor activity of Gl-BSP may mainly relate to the activation of the immune response of the host organism by the stimulation of NK cells, T cells, and macrophages.

  3. Comparison of in vivo toxicity, antioxidant and immunomodulatory activities of coconut, nipah and pineapple juice vinegars.

    Science.gov (United States)

    Mohamad, Nurul Elyani; Keong Yeap, Swee; Beh, Boon Keen; Romli, Muhammad Firdaus; Yusof, Hamidah Mohd; Kristeen-Teo, Ye Wen; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

    2018-01-01

    Vinegar is widely used as a food additive, in food preparation and as a food supplement. This study compared the phenolic acid profiles and in vivo toxicities, and antioxidant and immunomodulatory effects of coconut, nipah and pineapple juice vinegars, which were respectively prepared via a two-step fermentation using Saccharomyces cerevisiae 7013 INRA and Acetobacter aceti vat Europeans. Pineapple juice vinegar, which had the highest total phenolic acid content, also exhibited the greatest in vitro antioxidant capacity compared to coconut juice and nipah juice vinegars. Following acute and sub-chronic in vivo toxicity evaluation, no toxicity and mortality were evident and there were no significant differences in the serum biochemical profiles between mice administered the vinegars versus the control group. In the sub-chronic toxicity evaluation, the highest liver antioxidant levels were found in mice fed with pineapple juice vinegar, followed by coconut juice and nipah juice vinegars. However, compared to the pineapple juice and nipah juice vinegars, the mice fed with coconut juice vinegar, exhibited a higher population of CD4 + and CD8 + T-lymphocytes in the spleen, which was associated with greater levels of serum interleukin-2 and interferon-γ cytokines. Overall, the data suggested that not all vinegar samples cause acute and sub-chronic toxicity in vivo. Moreover, the in vivo immunity and organ antioxidant levels were enhanced, to varying extents, by the phenolic acids present in the vinegars. The results obtained in this study provide appropriate guidelines for further in vivo bioactivity studies and pre-clinical assessments of vinegar consumption. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  4. Estragole and methyl-eugenol-free extract of Artemisia dracunculus possesses immunomodulatory effects

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    Seyyed Meysam Abtahi Froushani

    2016-08-01

    Full Text Available Objective: Some evidence suggests that chronic uptake of estragole and methyl-eugenol, found in the essential oil of Artemisia dracunculus (tarragon, may be associated with an increased risk of hepato-carcinogenicity. The present study was conducted to investigate the immumodulatory and anti-inflammatory potentials of estragole and methyl-eugenol free extract of tarragon. Materials and Methods: Aqueous, hydroalcoholic, methanol and hexane extracts of dried and milled tarragon was prepared and analyzed by GC-MS. The estragole and methyl-eugenol free extract was characterized and used for evaluation of immunity in NMRI mice after challenging with sheep red blood cells. Results: It was shown that the aqueous extract of tarragon was free from potentially harmful estragole or methyl-eugenol. Moreover, the immunomodulatory effect of the aqueous extract of tarragon (100 mg/kg for 21 consecutive days was investigated. The extract significantly increased the level of anti-sheep red blood cells (SRBC (antibody and simultaneously decreased the level of cellular immunity in the treatment group. Moreover, tarragon caused a significant reduction in the production of pro-inflammatory IL-17 and IFN-γ in parallel with a reduction in the ratio of INF-γ to Il-10 or IL-17 to IL-10 in the splenocytes. In addition, the levels of the respiratory burst and nitric oxide production in peritoneal macrophages were significantly decreased. Additionally, the phagocytosis potential of macrophages was significantly increased in treated mice. Conclusion: These data showed that the aqueous extract of tarragon may be used as a natural source to modulate the immune system, because it can inhibit pro-inflammatory cytokines and induce anti-inflammatory macrophages.

  5. Improving Social Skills in Adolescents and Adults with Autism and Severe to Profound Intellectual Disability: A Review of the Literature

    Science.gov (United States)

    Walton, Katherine M.; Ingersoll, Brooke R.

    2013-01-01

    Social skills are important treatment targets for individuals with autism spectrum disorders (ASD) across the lifespan. However, few treatments are available for adolescents and adults with ASD who also have severe to profound intellectual disability (S/PID). Several social skill interventions have been described that may improve social skills in…

  6. The Hands with Eyes and Nose in the Palm: As Effective Communication Alternatives for Profoundly Deaf People in Zimbabwe

    Science.gov (United States)

    Mutswanga, Phillipa

    2017-01-01

    Drawing from the experiences and testimonies of people with profound deafness, the study qualitatively explored the use of the hands with eyes and nose in the palm as communication alternatives in the field of deafness. The study was prompted by the 27 year old lady, Leah Katz-Hernandez who is deaf who got engaged in March 2015 as the 2016…

  7. How to Facilitate Transition to Adulthood? Innovative Solutions from Parents of Young Adults with Profound Intellectual Disability

    Science.gov (United States)

    Gauthier-Boudreault, Camille; Couture, Mélanie; Gallagher, Frances

    2018-01-01

    Background: At age 21, access to specialised services for youth with profound intellectual disability is reduced. Few studies have focused on parents' views concerning potential solutions to ease the transition to adulthood, and most existing solutions target young adults with less severe intellectual disability. The aim of this study is to…

  8. Reliability of assessing the sensory perception of children with profound intellectual and multiple disabilities : a case study

    NARCIS (Netherlands)

    Vlaskamp, C.; Cuppen-Fonteine, H.

    Background This study describes preliminary stages of developing a checklist to enable practitioners to determine the behavioural responses of children with profound intellectual and multiple disabilities to sensory stimuli. Reliability of currently used checklists is low, with a focus on the

  9. Motor activation in people with profound intellectual and multiple disabilities: research in daily practice in residential facilities

    NARCIS (Netherlands)

    Bossink, Leontien; van der Putten, Annette; Vlaskamp, Carla

    2014-01-01

    Aim: The total study aims at generating knowledge about the best way to motor activate persons with profound intellectual and multiple disabilities (PIMD) in residential facilities. The purpose of the current poster presentation is to present the results of the first step executed in this project

  10. Parental Adaptation to Out-of-Home Placement of a Child with Severe or Profound Developmental Disabilities

    Science.gov (United States)

    Jackson, Jeffrey B.; Roper, Susanne Olsen

    2014-01-01

    Utilizing grounded theory qualitative research methods, a model was developed for describing parental adaptation after voluntary placement of a child with severe or profound developmental disabilities in out-of-home care. Interviews of parents from 20 families were analyzed. Parents' cognitive appraisals of placement outcomes were classified…

  11. The documentation of health problems in relation to prescribed medication in people with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    van der Heide, D. C.; van der Putten, A. A. J.; van den Berg, P. B.; Taxis, K.; Vlaskamp, C.

    Persons with profound intellectual and multiple disabilities (PIMD) suffer from a wide range of health problems and use a wide range of different drugs. This study investigated for frequently used medication whether there was a health problem documented in the medical notes for the drug prescribed.

  12. You Should be Dancin:! The Role of Performing Arts in the Lives of the Severely and Profoundly Handicapped.

    Science.gov (United States)

    Barringer, Mary Dean

    The manual presents a program planning framework and teaching units for teaching dance and movement to severely and profoundly handicapped individuals. The planning framework contains four components: (1) aesthetic perception/multisensory integration; (2) creative expression; (3) dance heritage/historical and cultural; and (4) aesthetic…

  13. Domains of quality of life of people with profound multiple disabilities : The perspective of parents and direct support staff

    NARCIS (Netherlands)

    Petry, K; Maes, B; Vlaskamp, C

    Background This study considered the general validity of the basic domains of quality of life that appear in theoretical models, in relation to people with profound multiple disabilities. The authors examined how parents and direct support staff operationalized these basic domains for people with

  14. Camera-based microswitch technology to monitor mouth, eyebrow, and eyelid responses of children with profound multiple disabilities

    NARCIS (Netherlands)

    Lancioni, G.E.; Bellini, D.; Oliva, D.; Singh, N.N.; O'Reilly, M.F.; Sigafoos, J.; Lang, R.B.; Didden, H.C.M.

    2011-01-01

    A camera-based microswitch technology was recently used to successfully monitor small eyelid and mouth responses of two adults with profound multiple disabilities (Lancioni et al., Res Dev Disab 31:1509-1514, 2010a). This technology, in contrast with the traditional optic microswitches used for

  15. The Effect of Frequency Transposition on Speech Perception in Adolescents and Young Adults with Profound Hearing Loss

    Science.gov (United States)

    Gou, J.; Smith, J.; Valero, J.; Rubio, I.

    2011-01-01

    This paper reports on a clinical trial evaluating outcomes of a frequency-lowering technique for adolescents and young adults with severe to profound hearing impairment. Outcomes were defined by changes in aided thresholds, speech perception, and acceptance. The participants comprised seven young people aged between 13 and 25 years. They were…

  16. Informal Social Networks of People with Profound Intellectual and Multiple Disabilities: Relationship with Age, Communicative Abilities and Current Living Arrangements

    Science.gov (United States)

    Kamstra, A.; van der Putten, A. A. J.; Post, W. J.; Vlaskamp, C.

    2015-01-01

    Background: People with profound intellectual and multiple disabilities (PIMD) have limited informal social contacts. Research to determine the factors which can positively influence establishing sound informal social contacts is required. Materials and Methods: Regression analysis for 200 people with PIMD was used to analyse how age,…

  17. Family matters : The experiences and opinions of family members of persons with (severe) or profound intellectual disabilities

    NARCIS (Netherlands)

    Luijkx, Jorien

    2016-01-01

    “I love my sister, but sometimes I don’t”. This is one of the statements made in the study focused on the experiences of family members of people with (profound) intellectual (and multiple) disabilities (both of individuals living in a residential facility as persons living at home). In recent

  18. An Evaluation of Social and Adaptive Skills in Adults with Bipolar Disorder and Severe/Profound Intellectual Disability

    Science.gov (United States)

    Matson, Johnny L.; Terlonge, Cindy; Gonzalez, Melissa L.; Rivet, Tessa

    2006-01-01

    The purpose of this study was to explore the interrelationship of social and adaptive skills in adults with bipolar disorder and severe or profound intellectual disability. A bipolar group (N=14), a severe psychopathology group without bipolar disorder (N=14), and a control group with no DSM-IV Axis I diagnosis (N=14) were compared on the…

  19. Therapeutic interventions in the Netherlands and Belgium in support of people with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    Vlaskamp, Carla; Nakken, Han

    For several reasons, people with profound and multiple disabilities may be offered a variety of therapeutic interventions. Thus far, researchers have shown a limited interest in providing an empirical base for these interventions. Research is needed on the theoretical rationale (if any), the

  20. The Role of the External Personal Assistants for Children with Profound Intellectual and Multiple Disabilities Working in the Children's Home

    Science.gov (United States)

    Axelsson, Anna Karin

    2015-01-01

    Background: Children with profound intellectual and multiple disabilities need support to function in an optimal way. However, there is a limited knowledge about the role of external personal assistants working in the children's home. Materials and Methods: A mixed method study was performed including qualitative data from interviews with 11…

  1. Catch the wave! Time-window sequential analysis of alertness stimulation in individuals with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    Munde, V. S.; Vlaskamp, C.; Maes, B.; Ruijssenaars, A. J. J. M.

    BackgroundWhile optimally activities are provided at those moments when the individual with profound intellectual and multiple disabilities (PIMD) is focused on the environment' or alert', detailed information about the impact that the design and timing of the activity has on alertness is lacking.

  2. Noonan Syndrome: An Underestimated Cause of Severe to Profound Sensorineural Hearing Impairment. Which Clues to Suspect the Diagnosis?

    Science.gov (United States)

    Ziegler, Alban; Loundon, Natalie; Jonard, Laurence; Cavé, Hélène; Baujat, Geneviève; Gherbi, Souad; Couloigner, Vincent; Marlin, Sandrine

    2017-09-01

    To highlight Noonan syndrome as a clinically recognizable cause of severe to profound sensorineural hearing impairment. New clinical cases and review. Patients evaluated for etiological diagnosis by a medical geneticist in a reference center for hearing impairment. Five patients presenting with confirmed Noonan syndrome and profound sensorineural hearing impairment. Diagnostic and review of the literature. Five patients presented with profound sensorineural hearing impairment and molecularly confirmed Noonan syndrome. Sensorineural hearing impairment has been progressive for three patients. Cardiac echography identified pulmonary stenosis in two patients and was normal for the three other patients. Short stature was found in two patients. Mild intellectual disability was found in one patient. Inconspicuous clinical features as facial dysmorphism, cryptorchidism, or easy bruising were of peculiar interest to reach the diagnosis of Noonan syndrome. Profound sensorineural hearing impairment can be the main feature of Noonan syndrome. Associated features are highly variable; thus, detailed medical history and careful physical examination are mandatory to consider the diagnosis in case of a sensorineural hearing impairment.

  3. Quality-Enhancing Interventions for People with Profound Intellectual and Multiple Disabilities: A Review of the Empirical Research Literature

    Science.gov (United States)

    Maes, Bea; Lambrechts, Greet; Hostyn, Ine; Petry, Katja

    2007-01-01

    Background: This study provides an overview of empirical research on the effectiveness of quality-enhancing interventions for people with profound intellectual and multiple disabilities (PIMD). Method: Through computerised searches of the PsycINFO and ERIC databases, and using several search criteria specifically relating to the target group and…

  4. Staff attributions of the causes of challenging behaviour in children and adults with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    Poppes, P.; van der Putten, A.A.J.; ten Brug, A.; Vlaskamp, C.

    A study has shown that staff do not generally perceive challenging behaviour in people with profound intellectual and multiple disabilities (PIMD) as being of serious consequence. In this study we aimed to gain a better understanding of the causal explanations that direct care and support staff give

  5. Physicochemical Characterization of Polysaccharides with Macrophage Immunomodulatory Activities Isolated from Red Ginseng (Panax ginseng C. A. Meyer

    Directory of Open Access Journals (Sweden)

    Liang Zheng

    2017-01-01

    Full Text Available In this study, four polysaccharide fractions designated as RGP1, RGP2, RGP3, and RGP4 were isolated from red ginseng by DEAE-52 cellulose chromatography, and their macrophage immunomodulatory activities were investigated. The results revealed that the proliferation, NO production, and neutral red phagocytosis of RAW 264.7 macrophage cells in groups treated with RGP1 and RGP2 in vitro were increased significantly compared to RGP3 and RGP4. In addition, the level of TNF-α in RAW 264.7 cells was significantly increased in RGP1 and RGP2 groups. All the results consistently indicated that polysaccharide fractions RGP1 and RGP2 had strong macrophage immunomodulatory activities. Furthermore, RGP1 and RGP2 were purified by Sephadex G-100 column and RGP2 was further fractionated into a homogeneous fraction RGP2-1, with the molecular weight of 2.16 × 104 Da. The analysis of monosaccharide composition revealed that RGP1 was composed of arabinose, glucose, and galactose with a relative molecular ratio of 0.02 : 0.88 : 0.10. RGP2-1 was composed of rhamnose, arabinose, glucose, and galactose with a relative molecular ratio of 0.02 : 0.10 : 0.77 : 0.11. These results provided evidences that the neutral polysaccharide fractions RGP1 and RGP2 possessed significant immunomodulatory activity and could be explored as a promising natural immunomodulating agent applied in functional foods or medicines.

  6. Characterization and immunomodulatory effects of glucans from Pleurotus albidus, a promising species of mushroom for farming and biomass production.

    Science.gov (United States)

    Castro-Alves, Victor Costa; Gomes, Daniel; Menolli, Nelson; Sforça, Maurício Luís; Nascimento, João Roberto Oliveira do

    2017-02-01

    Polysaccharides from a number of mushroom species are recognized as functional food ingredients with potential health benefits, including immunomodulatory effects. In this study, polysaccharides extracted from the basidiome with cold water (BaCW), hot water (BaHW), and hot alkali (BaHA) solution, and exo- (MyEX) and endopolysaccharides (MyEN) from the submerged culture of Pleurotus albidus, a promising species for farming and biomass production, were analyzed for their chemical composition and structure and immunomodulatory effects on macrophages. Compositional (HPAEC-PAD and HPSEC-RID/MWD) and structural (FT-IR, 1D- and 2D-NMR) analyses identified BaCW and MyEX as β-(1,6)-branched β-(1,3)-glucans, BaHW and MyEN as α-(1,3)-(1,2)-branched α-(1,6)-glucans, and BaHA as a mixture of α-(1,6)- and β-(1,3)-glucans. BaCW and MyEX stimulated the production of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO), but not interleukin-6 (IL-6), and decreased phagocytosis of zymosan particles. In contrast, BaHW and MyEN induced TNF-α, NO and IL-6 production, and increased zymosan phagocytosis, while BaHA displayed intermediary effects in comparison the other polysaccharides. In conclusion, the basidiome and the submerged culture of P. albidus are sources of easily extractable α- and β-glucans with potential immunomodulatory effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Efficacy of immunomodulatory therapy with interferon-β or glatiramer acetate on multiple sclerosis-associated uveitis.

    Science.gov (United States)

    Velazquez-Villoria, D; Macia-Badia, C; Segura-García, A; Pastor Idoate, S; Arcos-Algaba, G; Velez-Escola, L; García-Arumí, J

    2017-06-01

    To analyse the role of interferon-β or glatiramer acetate in reducing the inflammatory episodes of intra-ocular inflammation in multiple sclerosis-associated uveitis. A study was conducted on a non-randomised, retrospective case series of 13 patients with proven multiple sclerosis and uveitis (minimum follow-up, 12 months). All patients were given immunomodulatory treatment (interferon-β or glatiramer acetate) to control the course of the multiple sclerosis. Patients were compared to themselves before initiating the treatment, in order to assess the difference in uveitis episodes. The main outcome measurements were the number of uveitis episodes with/without immunomodulatory treatment. Uveitis was bilateral in 10 (77%) out of 13 patients. Intermediate uveitis was observed in 11 patients, retinal vasculitis in 3 patients, and one patient was classified as a posterior uveitis. The patients had a mean of 4.15±3.1 episodes of uveitis (range 1-10) during the follow-up period (148.6±84.3 months). When compared to their pre-treatment status, patients on treatment with interferon-β or glatiramer acetate showed a significant decrease of 0.36 episodes of ocular inflammation per year (P=.02). Mild side effects related to immunomodulatory treatment were observed in 6 (46%) patients, 3 (23%) patients with a flu-like syndrome, and 3 (23%) patients with a skin rash. Interferon β or glatiramer acetate could be effective in reducing the uveitis episodes in patients with multiple sclerosis-associated uveitis, and was well tolerated in most patients. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Immunomodulatory factors in cervicovaginal secretions from pregnant and non-pregnant women: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Stek Alice

    2011-09-01

    Full Text Available Abstract Background Pregnant women are at an increased risk for HIV infection due to unknown biological causes. Given the strong effect of sex-hormones on the expression of immunomuodulatory factors, the central role of mucosal immunity in HIV pathogenesis and the lack of previous studies, we here tested for differences in immunomuodulatory factors in cervico-vaginal secretions between pregnant and non-pregnant women. Methods We compared concentrations of 39 immunomodulatory factors in cervicovaginal lavages (CVL from 21 pregnant women to those of 24 non-pregnant healthy women from the US. We used Bonferroni correction to correct for multiple testing and linear regression modeling to adjust for possible confounding by plasma cytokine concentration, cervical ectopy, total protein concentration, and other possible confounders. Cervical ectopy was determined by planimetry. Concentration of immunomodulatory factors were measured by a multiplex assay, protein concentration by the Bradford Method. Results Twenty six (66% of the 39 measured immunomodulatory factors were detectable in at least half of the CVL samples included in the study. Pregnant women had threefold lower CVL concentration of CCL22 (geometric mean: 29.6 pg/ml versus 89.7 pg/ml, p = 0.0011 than non-pregnant women. CVL CCL22 concentration additionally correlated negatively with gestational age (Spearman correlation coefficient [RS]: -0.49, p = 0.0006. These associations remained significant when corrected for multiple testing. CCL22 concentration in CVL was positively correlated with age and negatively correlated with time since last coitus and the size of cervical ectopy. However, none of these associations could explain the difference of CCL22 concentration between pregnant and non-pregnant women in this study, which remained significant in adjusted analysis. Conclusions In this study population, pregnancy is associated with reduced concentrations of CCL22 in cervicovaginal secretions

  9. Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative.

    Science.gov (United States)

    Dick, Andrew D; Rosenbaum, James T; Al-Dhibi, Hassan A; Belfort, Rubens; Brézin, Antoine P; Chee, Soon Phaik; Davis, Janet L; Ramanan, Athimalaipet V; Sonoda, Koh-Hei; Carreño, Ester; Nascimento, Heloisa; Salah, Sawsen; Salek, Sherveen; Siak, Jay; Steeples, Laura

    2018-05-01

    An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations

  10. The immunomodulatory protein RH36 is relating to blood-feeding success and oviposition in hard ticks.

    Science.gov (United States)

    Wang, Fangfang; Lu, Xiaojuan; Guo, Fengxun; Gong, Haiyan; Zhang, Houshuang; Zhou, Yongzhi; Cao, Jie; Zhou, Jinlin

    2017-06-15

    An immunomodulatory protein designated RH36 was identified in the tick Rhipicephalus haemaphysaloides. The cDNA sequence of RH36 has 844bp and encodes a deduced protein with a predicted molecular weight of 24kDa. Bioinformatics analysis indicated that RH36 presented a degree of similarity of 34.36% with the immunomodulatory protein p36 from the tick Dermacentor andersoni. The recombinant RH36 (rRH36) expressed in Sf9 insect cells suppressed the T-lymphocyte mitogen-driven in vitro proliferation of splenocytes and the expression of several cytokines such as IL-2, IL-12, and TNF-α. Furthermore, the proliferation of splenocytes isolated from rRH36-inoculated mice was significantly lower than that in control mice, suggesting that rRH36 could directly suppress immune responses in vivo. In addition, microarray analysis of splenocytes indicated that the expression of several immunomodulatory genes was downregulated by rRH36. The silencing of the RH36 gene by RNAi led to a 37.5% decrease in the tick attachment rate 24h after placement into the rabbit ears, whereas vaccination with RH36 caused a 53.06% decrease in the tick engorgement rate. Unexpectedly, RNAi induced a significant decrease in the oviposition rate, ovary weight at day 12 after engorgement, and egg-hatching rate. The effects of RH36 on blood feeding and oviposition were further confirmed by vaccination tests using the recombinant protein. These results indicate that RH36 is a novel member of immunosuppressant proteins and affects tick blood feeding and oviposition. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Postural control in children with typical development and children with profound hearing loss

    Directory of Open Access Journals (Sweden)

    Monteiro de Sousa AM

    2012-05-01

    Full Text Available Aneliza Maria Monteiro de Sousa,1 Jônatas de França Barros,2 Brígido Martins de Sousa Neto31Faculty of Health Sciences, University of Brasilia, Brasilia, Federal District, Brazil; 2Department of Physical Education at the Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil; 3University Center UNIEURO, Brasilia, Federal District, BrazilPurpose: To describe the behavior of the postural control in children with profound sensorineural hearing loss and compare the results of experimental tests with hearing children aged 7 to 10 years.Patients and methods: This is a cross-sectional study where 100 children were divided into experimental and control groups. We used a force platform, AccuSway Plus, where the tests were conducted under the experimental conditions: open base, eyes open (OBEO; open base, eyes closed (OBEC; closed base, eyes open (CBEO; closed base, eyes closed (CBEC. The body sway velocity (V of the center of pressure, the displacement in the anteroposterior direction (COPap and mediolateral (COPml of the center of pressure were the parameters to evaluate the postural control. For statistical analysis we used the nonparametric Mann–Whitney U test, with a significance level of 5%.Results: In comparisons of variables between the groups, the experimental group outperformed by at least 75% of the control group values. In terms of global trends, the experimental group shows higher values of body oscillations in all experimental conditions and variables evaluated. Children with hearing loss had poorer balance performance compared to the group of hearing. The inferential analysis revealed a statistically significant difference in the balance between deaf and hearing children in the OBEC experimental condition in relation to the COPml parameter (P = 0.04. There were no statistically significant differences in comparisons between the sexes when the groups were analyzed separately. The prevalence of unknown etiology

  12. Binaural auditory outcomes in patients with postlingual profound unilateral hearing loss: 3 years after cochlear implantation.

    Science.gov (United States)

    Mertens, Griet; Kleine Punte, Andrea; De Bodt, Marc; Van de Heyning, Paul

    2015-01-01

    The value of cochlear implants (CI) in patients with profound unilateral hearing loss (UHL) and tinnitus has recently been investigated. The authors previously demonstrated the feasibility of CI in a 12- month outcome study in a prospective UHL cohort. The aim of this study was to investigate the binaural auditory outcomes in this cohort 36 months after CI surgery. The 36-month outcome was evaluated in 22 CI users with postlingual UHL and severe tinnitus. Twelve subjects had contralateral normal hearing (single-sided deafness - SSD group) and 10 subjects had a contralateral, mild to moderate hearing loss and used a hearing aid (asymmetric hearing loss - AHL group). Speech perception in noise was assessed in two listening conditions: the CIoff and the CIon condition. The binaural summation effect (S0N0), binaural squelch effect (S0NCI) and the combined head shadow effect (SCIN0) were investigated. Subjective benefit in daily life was assessed by means of the Speech, Spatial and Qualities of Hearing Scale (SSQ). At 36 months, a significant binaural summation effect was observed for the study cohort (2.00, SD 3.82 dB; p binaural effect was not significant 12 months after CI surgery. A binaural squelch effect was significant for the AHL subgroup at 12 months (2.00, SD 4.38 dB; p < 0.05). A significant combined head shadow and squelch effect was also noted in the spatial configuration SCIN0 for the study cohort (4.00, SD 5.89 dB; p < 0.01) and for the AHL subgroup (5.67, SD 6.66 dB; p < 0.05). The SSQ data show that the perceived benefit in daily life after CI surgery remains stable up to 36 months at CIon. CI can significantly improve speech perception in noise in patients with UHL. The positive effects of CIon speech perception in noise increase over time up to 36 months after CI surgery. Improved subjective benefit in daily life was also shown to be sustained in these patients. © 2015 S. Karger AG, Basel.

  13. Experience with cochlear implants in Greenlanders with profound hearing loss living in Greenland

    Directory of Open Access Journals (Sweden)

    Preben Homøe

    2013-08-01

    Full Text Available Objective. Cochlear implant (CI treatment was introduced to the world in the 1980s and has become a routine treatment for congenital or acquired severe-to-profound hearing loss. CI treatment requires access to a highly skilled team of ear, nose and throat specialists, audiologists and speech-language pathologists for evaluation, surgery and rehabilitation. In particular, children treated with CI are in need of long-term post-operative auditory training and other follow-up support. Design. The study is retrospective with updated information on present performance. Results. Since 2001, a total of 11 Greenlandic patients living in Greenland have been treated with CI, 7 children and 4 adults. Of these children, 4 use oral communication only and are full-time CI-users, 2 with full-time use of CI are still in progress with use of oral communication, and 1 has not acquired oral language yet, but has started auditory and speech training. Six children attend mainstream public school while one child is in kindergarten. Of the adults, only 1 has achieved good speech perception with full-time use of CI while 3 do not use the CI. Discussion. From an epidemiological point of view, approximately 1–3 children below 6 years are in need of a CI every second year in Greenland often due to sequelae from meningitis, which may cause postinfectious deafness. Screening of new-borns for hearing has been started in Greenland establishing the basis for early diagnosis of congenital hearing impairment and subsequent intervention. The logistics and lack of availability of speech therapists in Greenland hampers possibilities for optimal language and speech therapy of CI patients in Greenland. This study aims at describing the results of CI treatment in Greenlanders and the outcome of the CI operations along with the auditory and speech/language outcomes. Finally, we present a suggestion for the future CI treatment and recommendations for an increased effort in the

  14. Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials.

    Science.gov (United States)

    Franz, Sandra; Rammelt, Stefan; Scharnweber, Dieter; Simon, Jan C

    2011-10-01

    A key for long-term survival and function of biomaterials is that they do not elicit a detrimental immune response. As biomaterials can have profound impacts on the host immune response the concept emerged to design biomaterials that are able to trigger desired immunological outcomes and thus support the healing process. However, engineering such biomaterials requires an in-depth understanding of the host inflammatory and wound healing response to implanted materials. One focus of this review is to outline the up-to-date knowledge on immune responses to biomaterials. Understanding the complex interactions of host response and material implants reveals the need for and also the potential of "immunomodulating" biomaterials. Based on this knowledge, we discuss strategies of triggering appropriate immune responses by functional biomaterials and highlight recent approaches of biomaterials that mimic the physiological extracellular matrix and modify cellular immune responses. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Mesenchymal Stem Cells in Organ Transplantation: Immunomodulatory properties of mesenchymal stem cells for application in organ transplantation

    OpenAIRE

    Crop, Meindert

    2010-01-01

    textabstractKidney transplantation is the only effective treatment for patients with end-stage renal disease. Transplantation of a donor organ, however, leads to recognition of the foreign donor antigens by the recipient’s immune system, resulting in rejection of the graft. In addition, ischemia-reperfusion injury leads to the initiation of immune responses. To prevent graft rejection, transplant recipients need to use life-long immunosuppressive medication. These drugs, however, can lead to ...

  16. Isolation of the intracellular and extracellular polysaccharides of Ganoderma neojaponicum (Imazeki and characterization of their immunomodulatory properties

    Directory of Open Access Journals (Sweden)

    Nik Hafizah Nik Ubaidillah

    2015-05-01

    Conclusion: The findings of this study indicate that the IPSs and EPSs of G. neojaponicum have the potential to be used as immunomodulating agents to stimulate the innate immune system for fighting infectious diseases. The polysaccharides from G. neojaponicum have to be further commercially explored as an alternative for medicinal Ganoderma variety of G. lucidum production.

  17. TAHLAB (SPIRULINA) AND FEW OTHER MEDICINAL PLANTS HAVING ANTI-OXIDANT & IMMUNOMODULATORY PROPERTIES DESCRIBED IN UNANI MEDICINE - A REVIEW

    OpenAIRE

    Md. Anzar Alam*, Nafis Haider , Shamim Ahmed , Md. Tanwir Alam and Abdul Azeez

    2013-01-01

    : Antioxidants are substances that may protect cells from the damage caused by unstable molecules known as free radicals; free radicals damage may lead to cancer and other diseases. Some of the example of antioxidants are like β-carotene, lycopene, Vit. C, E & A and other substances which are found in variety of fruits, vegetables, algae (spirulina) & other medicinal plants. Spirulina (Blue green algae) is a microscopic single cell alga which grows in fresh water and has a simple structure bu...

  18. Mesenchymal stromal cells express GARP/LRRC32 on their surface: effects on their biology and immunomodulatory capacity.

    Science.gov (United States)

    Carrillo-Galvez, Ana Belén; Cobo, Marién; Cuevas-Ocaña, Sara; Gutiérrez-Guerrero, Alejandra; Sánchez-Gilabert, Almudena; Bongarzone, Pierpaolo; García-Pérez, Angélica; Muñoz, Pilar; Benabdellah, Karim; Toscano, Miguel G; Martín, Francisco; Anderson, Per

    2015-01-01

    Mesenchymal stromal cells (MSCs) represent a promising tool for therapy in regenerative medicine, transplantation, and autoimmune disease due to their trophic and immunomodulatory activities. However, we are still far from understanding the mechanisms of action of MSCs in these processes. Transforming growth factor (TGF)-β1 is a pleiotropic cytokine involved in MSC migration, differentiation, and immunomodulation. Recently, glycoprotein A repetitions predominant (GARP) was shown to bind latency-associated peptide (LAP)/TGF-β1 to the cell surface of activated Foxp3(+) regulatory T cells (Tregs) and megakaryocytes/platelets. In this manuscript, we show that human and mouse MSCs express GARP which presents LAP/TGF-β1 on their cell surface. Silencing GARP expression in MSCs increased their secretion and activation of TGF-β1 and reduced their proliferative capacity in a TGF-β1-independent manner. Importantly, we showed that GARP expression on MSCs contributed to their ability to inhibit T-cell responses in vitro. In summary, we have found that GARP is an essential molecule for MSC biology, regulating their immunomodulatory and proliferative activities. We envision GARP as a new target for improving the therapeutic efficacy of MSCs and also as a novel MSC marker. © 2014 AlphaMed Press.

  19. An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles

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    Karin Pachler

    2017-07-01

    Full Text Available The regenerative and immunomodulatory activity of mesenchymal stromal cells (MSCs is partially mediated by secreted vesicular factors. Extracellular vesicles (EVs exocytosed by MSCs are gaining increased attention as prospective non-cellular therapeutics for a variety of diseases. However, the lack of suitable in vitro assays to monitor the therapeutic potential of EVs currently restricts their application in clinical studies. We have evaluated a dual in vitro immunomodulation potency assay that reproducibly reports the inhibitory effect of MSCs on induced T-cell proliferation and the alloantigen-driven mixed leukocyte reaction of pooled peripheral blood mononuclear cells in a dose-dependent manner. Phytohemagglutinin-stimulated T-cell proliferation was inhibited by MSC-derived EVs in a dose-dependent manner comparable to MSCs. In contrast, inhibition of alloantigen-driven mixed leukocyte reaction was only observed for MSCs, but not for EVs. Our results support the application of a cell-based in vitro potency assay for reproducibly determining the immunomodulatory potential of EVs. Validation of this assay can help establish reliable release criteria for EVs for future clinical studies.

  20. Effects of vinegar–egg on growth inhibition, differentiation human leukemic U937 cells and its immunomodulatory activity

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    Shiu-Yu Wang

    2018-04-01

    Full Text Available Vinegar and eggs have rich nutrients. In this study, the mixed form of both derived products, vinegar–egg solution and its products (vinegar–egg concentrate and vinegar–egg condensate were chosen for an assessment of their biological activity. To further our understanding regarding the anticancer and immunomodulatory effects of vinegar–egg, we investigated its effects on the proliferation and differentiation of U937 cells. Vinegar–egg was treated using spray drying, freeze drying and vacuum concentration and used to stimulate human mononuclear cells. The conditioned media obtained from these cultures by filtration were used to treat U937 cells. Three conditioned media inhibited U937 cell growth by 22.1–67.25% more effectively than PHA-treated control (22.53%. CD11b and CD14 expression on the treated U937 cells were 29.1–45.4% and 31.6–47.2%, respectively. High levels of cytokines IL-1β, IFN-γ and TNF-α were detected in the three conditioned media. Vinegar–egg stimulates human mononuclear cells to secrete cytokines, which inhibit the growth of U937 cells and induce their differentiation. Keywords: Cytokines, Differentiation, Immunomodulatory activity, Leukemic U937 cells, Vinegar–egg

  1. Immunomodulatory effects of herbal formula of astragalus polysaccharide (APS) and polysaccharopeptide (PSP) in mice with lung cancer.

    Science.gov (United States)

    Zhou, Xing; Liu, Zijing; Long, Tingting; Zhou, Lijng; Bao, Yixi

    2018-01-01

    This study is to investigate the immunomodulatory effects of the herbal formula of astragalus polysaccharide (APS) and polysaccharopeptide (PSP) in mouse models of immunosuppression and lung cancer. Immune parameters were recorded for these model mice. Peripheral white blood cells (WBC) were detected with the automatic blood cell analyzer. Spleen and thymus indices, and tumor inhibition ratio were obtained. Percentage of peripheral blood CD4 + and CD8 + T lymphocytes were detected by flow cytometry. Serum levels of Th1 (IL-2, TNF, and IFN-γ), Th2 (IL-4, IL-6, and IL-10), and Th17 (IL-17A) were detected with the BD cytometric bead array (CBA) mouseTh1/Th2/Th17 cytokine kit. Compared with the NS group, the PSP and APS herbal formula significantly improved the WBC, thymus index, spleen index, CD4 + /CD8 + ratio, TNF, IFN-γ, IL-2, andIL-17Ainimmunosuppressivemice and lung cancer mice (PAPS herbal formula group (PAPS herbal formula group induced comparable tumor inhibiting effect with the AMD group (23.3% and 24.1%, respectively). The PSP+APS herbal formula have immunomodulatory effects and anti-tumor activity in mice with of lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Cytotoxic, Antitumor and Immunomodulatory Effects of the Water-Soluble Polysaccharides from Lotus (Nelumbo nucifera Gaertn. Seeds

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    Yafeng Zheng

    2016-11-01

    Full Text Available Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water–soluble polysaccharides from lotus seeds (LSPS were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant inhibitory effects on the mouse gastric cancer MFC cells, human liver cancer HuH-7 cells and mouse hepatocarcinoma H22 cells. The animal studies showed that LSPS inhibited tumor growth in H22 tumor-bearing mice with the highest inhibition rate of 45.36%, which is comparable to that induced by cyclophosphamide (30 mg/kg treatment (50.79%. The concentrations of white blood cells were significantly reduced in cyclophosphamide-treated groups (p < 0.01, while LSPS showed much fewer side effects according to the hematology analysis. LSPS improved the immune response in H22 tumor-bearing mice by enhancing the spleen and thymus indexes, and increasing the levels of serum cytokines including tumor necrosis factor-α and interleukin-2. Moreover, LSPS also showed in vivo antioxidant activity by increasing superoxide dismutase activity, thus reducing the malondialdehyde level in the liver tissue. These results suggested that LSPS can be used as an antitumor and immunomodulatory agent.

  3. The causal effect of profound organizational change when job insecurity is low – a quasi-experiment analysing municipal mergers

    DEFF Research Database (Denmark)

    Bhatti, Yosef; Gørtz, Mette; Pedersen, Lene Holm

    2015-01-01

    The present article finds that the causal effect of profound organizational change on employee health can be very low, if job insecurity is mitigated. We demonstrate this by investigating a rare case of a large-scale radical public sector reform with low job insecurity, in which a large number...... and job insecurity may explain the divergence from previous results. An important strength of our study is that the reform investigated can be considered a quasi-experiment, as it was exogenous and implemented simultaneously by the affected local governments. We also have access to an objective measure...... of robustness tests are performed, including propensity score matching and in-depth analysis of particular sub-groups of public sector employees. The results indicate that profound organizational change per se does not necessarily lead to decreased health, if job insecurity is low. However, a very modest effect...

  4. Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge

    Directory of Open Access Journals (Sweden)

    Roberts Paul C

    2009-04-01

    Full Text Available Abstract Background Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1, demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC. Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine. Results We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4 fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release. In vivo efficacy studies revealed that a single low dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against lethal influenza challenge in a mouse model and provides a more balanced Th1/Th2 humoral immune response, similar to live virus infections. Conclusion We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective.

  5. Managing Profound Suffering at the End-of-Life: Should expanding access to continuous deep sedation be the priority?

    Directory of Open Access Journals (Sweden)

    Kirby, Jeffrey

    2015-01-01

    Full Text Available This paper argues that in addressing and managing profound suffering at the end-of-life, the priority should not be the legalization of physician-assisted suicide or voluntary active euthanasia in jurisdictions where these practices are not currently available. Rather, concerted efforts should be made by society and the healthcare provider community to expand patient access to proportionate distress-relieving sedation and continuous deep sedation.

  6. The experience of black parents/caretakers with the births and care of a child with profound congenital defects

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    M.S. Mabaso

    1990-09-01

    Full Text Available The reaction of Black families to the birth and care of a baby with profound congenital defects was researched using twenty case studies. It was found that the families went through stages of the grieving process, that they shifted from the Western/Christian viewpoint to the traditional viewpoint in their struggle to cope and that they find the existing services grossly inadequate.

  7. Undernutrition in children with profound intellectual and multiple disabilities (PIMD): its prevalence and influence on quality of life.

    Science.gov (United States)

    Holenweg-Gross, C; Newman, C J; Faouzi, M; Poirot-Hodgkinson, I; Bérard, C; Roulet-Perez, E

    2014-07-01

    To estimate the prevalence of undernutrition among children with profound intellectual and multiple disabilities (PIMD) and to explore its influence on quality of life. Seventy-two children with PIMD (47 male; 25 female; age range 2 to 15 years 4 months; mean age 8.6, SD 3.6) underwent an anthropometric assessment, including body weight, triceps skinfold thickness, segmental measures and recumbent length. Undernutrition was determined using tricipital skinfold percentile and z-scores of weight-for-height and height-for-age. The quality of life of each child was evaluated using the QUALIN questionnaire adapted for profoundly disabled children. Twenty-five children (34.7%) were undernourished and seven (9.7%) were obese. Among undernourished children only eight (32 %) were receiving food supplements and two (8%) had a gastrostomy, of which one was still on a refeeding programme. On multivariate analysis, undernutrition was one of the independent predictors of lower quality of life. Undernutrition remains a matter of concern in children with PIMD. There is a need to better train professionals in systematically assessing the nutritional status of profoundly disabled children in order to start nutritional management when necessary. © 2013 John Wiley & Sons Ltd.

  8. Demonstration of ipsilateral brain activation by noise in patients profoundly deaf with cochlear implant, or unilaterally deaf

    International Nuclear Information System (INIS)

    Herzog, H.; Wieler, H.; Morgenstern, C.; Lipman, J.; Langen, K.-J.; Schmid, A.; Rota, E.; Patton, D.; Feinendegen, L.F.

    1986-01-01

    Two groups of patients with hearing handicaps have been investigated with PET and F-18-2-FDG. Since these patients were unilaterally deaf or profoundly deaf with a cochlear implant installed, monaural stimulation was possible excluding any effects of bone conduction to the contralateral ear. White noise was used as acoustic stimulus in unilaterally deaf patients. The peripheral auditory nerve of cochlear implant patients was stimulated by electrical impulses which were encoded from music or a 4-tone mixture by an electronic speech processor. The non-music stimuli were chosen to avoid associative cortical reactions. In both groups response to the stimuli by increase of glucose consumption (LCMRglc) was found not only in the contralateral primary auditory cortex as expected from neuroanatomical knowledge, but also in the ipsilateral auditory cortex. Furthermore there was no correlation between the hemisphere showing increased LCMRglc and the side of stimulation or the type of stimulus. The similarity of results obtained in both groups by acoustical and electrical stimulation of the auditory nerve suggests that this kind of measurement might be a tool to predict or check the performance of a cochlear implant in a profoundly deaf patient. The finding of increased LCMRglc in the area of the normal auditory cortex in patients profoundly deaf since birth contradicts the hypothesis of degeneration of this cortical center in such patients. (Author)

  9. In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamomum).

    Science.gov (United States)

    Majdalawieh, Amin F; Carr, Ronald I

    2010-04-01

    Although the immunomodulatory effects of many herbs have been extensively studied, research related to possible immunomodulatory effects of various spices is relatively scarce. Here, the potential immunomodulatory effects of black pepper and cardamom are investigated. Our data show that black pepper and cardamom aqueous extracts significantly enhance splenocyte proliferation in a dose-dependent, synergistic fashion. Enzyme-linked immunosorbent assay experiments reveal that black pepper and cardamom significantly enhance and suppress, respectively, T helper (Th)1 cytokine release by splenocytes. Conversely, Th2 cytokine release by splenocytes is significantly suppressed and enhanced by black pepper and cardamom, respectively. Experimental evidence suggests that black pepper and cardamom extracts exert pro-inflammatory and anti-inflammatory roles, respectively. Consistently, nitric oxide production by macrophages is significantly augmented and reduced by black pepper and cardamom, respectively. Remarkably, it is evident that black pepper and cardamom extracts significantly enhance the cytotoxic activity of natural killer cells, indicating their potential anti-cancer effects. Our findings strongly suggest that black pepper and cardamom exert immunomodulatory roles and antitumor activities, and hence they manifest themselves as natural agents that can promote the maintenance of a healthy immune system. We anticipate that black pepper and cardamom constituents can be used as potential therapeutic tools to regulate inflammatory responses and prevent/attenuate carcinogenesis.

  10. Inhibition of Tumor Growth and Immunomodulatory Effects of Flavonoids and Scutebarbatines of Scutellaria barbata D. Don in Lewis-Bearing C57BL/6 Mice

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    Tao Gong

    2015-01-01

    Full Text Available Immunomodulatory effect has been found to be an important therapeutic measure for immune responses against cancer. In this study, we evaluated the inhibition of Scutellaria barbata D. Don (SB, an anti-inflammatory and an antitumor Chinese herb, including flavonoids and scutebarbatines on tumor growth and its immunomodulatory effects in vivo. HPLC and LC/MS/MS methods were conducted for the analysis of flavonoids and scutebarbatines in SB. Lewis-bearing C57BL/6 mice model was established and tumor volume was evaluated by high frequency color ultrasound experiment. ELISA and western blot analysis were performed for the determination of immunomodulatory factors. SB treatment at the dose of 10, 6.67, and 3.33 g crude drug/kg/d significantly inhibited tumor growth of Lewis-bearing C57BL/6 mice with the inhibition rates of 44.41±5.44%, 33.56±4.85%, and 27.57±4.96%, respectively. More importantly, the spleen and thymus indexes were increased remarkably by SB treatment. SB could decrease IL-17, IL-10, FOXP3, TGF-β1, RORγt, and IL-6 levels whereas it could increase remarkably IL-2 and IFN-γ levels. Our results demonstrated that SB could inhibit tumor growth in vivo through regulating immune function in tumor-bearing mice and suggested that the immunomodulatory function of SB had a potential therapeutic effect in lung cancer.

  11. Transitioning hearing aid users with severe and profound loss to a new gain/frequency response: benefit, perception, and acceptance.

    Science.gov (United States)

    Convery, Elizabeth; Keidser, Gitte

    2011-03-01

    Adults with severe and profound hearing loss tend to be long-term, full-time users of amplification who are highly reliant on their hearing aids. As a result of these characteristics, they are often reluctant to update their hearing aids when new features or signal-processing algorithms become available. Due to the electroacoustic constraints of older devices, many severely and profoundly hearing-impaired adults continue to wear hearing aids that provide more low- and mid-frequency gain and less high-frequency gain than would be prescribed by the National Acoustic Laboratories' revised formula with profound correction factor (NAL-RP). To investigate the effect of a gradual change in gain/frequency response on experienced hearing-aid wearers with moderately severe to profound hearing loss. Double-blind, randomized controlled trial. Twenty-three experienced adult hearing-aid users with severe and profound hearing loss participated in the study. Participants were selected for inclusion in the study if the gain/frequency response of their own hearing aids differed significantly from their NAL-RP prescription. Participants were assigned either to a control or to an experimental group balanced for aided ear three-frequency pure-tone average (PTA) and age. Participants were fitted with Siemens Artis 2 SP behind-the-ear (BTE) hearing aids that were matched to the gain/frequency response of their own hearing aids for a 65 dB SPL input level. The experimental group progressed incrementally to their NAL-RP targets over the course of 15 wk, while the control group maintained their initial settings throughout the study. Aided speech discrimination testing, loudness scaling, and structured questionnaires were completed at 3, 6, 9, 12, and 15 wk postfitting. A paired comparison between the old and new gain/frequency responses was completed at 1 and 15 wk postfitting. Statistical analysis was conducted to examine differences between the experimental and control groups and changes

  12. Immunomodulatory effects of testosterone evaluated in all-trans retinoic acid differentiated HL-60 cells, granulocytes, and monocytes

    DEFF Research Database (Denmark)

    Boje, Alex; Moesby, Lise; Timm, Michael

    2012-01-01

    The sex hormones are known to affect innate immunity in humans. In this study we evaluated the immunomodulatory effects of testosterone in a model system comprising of all-trans retinoic acid differentiated HL-60 cells, and confirmed the results in human granulocytes and monocytes. Results showed...... that testosterone at pharmacological doses reduced the production of interleukin-8 and reactive oxygen species from differentiated HL-60 cells in a concentration dependent manner without affecting phagocytosis. The cells were stimulated with zymosan, lipopolysaccharide, or Bacillus subtilis. At the highest...... concentration of testosterone (120 µM), interleukin-8 secretion was reduced 42-80%, and production of reactive oxygen species was reduced 32-46%. Flutamide, an antagonist of the classical intracellular androgen receptor, was unable to antagonize the immunosuppressive effect of testosterone. We further...

  13. Comparison of Irrational Believes between Mothers of Severe or Profound Mentally Handicapped Children with Healthy Children Mothers

    Directory of Open Access Journals (Sweden)

    Behrouz Hivadi

    2007-10-01

    Full Text Available Objective: The purpose of present research was the comparison of mothers irrational believes with severe or profound mentally handicapped child and mothers with normal child from 6 to14 years old in Tehran city. Materials & Methods: This study was an analytical, cross – sectional and comparative (case – control research. From mothers with severe or profound mentally handicapped child who had refered to Tehran welfare services centers, 80 mothers were selected by regular randomized sampling from two rehabilitation centers and 80 mothers with normal child were selected for peering with the group of testimonial from schools areas of east, west, south, north and center of Tehran, through multi - stage cluster sampling in for variables of: age of mothers, educational levels, the location of living and the number of children. They answered to questionnaire of irrational believes of jons (IBT. Analysis of data was done by descriptive and infringing statistics methods (Independent T test, U Mann Whitney, Chi-square and fisher. Results: The findings showed that: there are significantly differences in total irrational believes and irrational believes of blame proneness, frustration reactive, anxious over concern, problem avoiding and dependency, perfectionism between two groups of mothers (P<0/05. There was no significant difference in irrational believes between mothers who had mental handicap daughter and mothers who had mental handicap son (P=0/314. There was no significantly difference between two groups of mothers in four believes of demand for approval (P=0/737, high-self expectation (P=0/126, emotional irresponsibility (P=0/727, helplessness for change (p=0/283. Conclusion: Irrational believes and many its sub scales. In mothers of severe or profound mental handicap children were more than mothers with normal child. But believes of demand for approval, high self expectation, emotional irresponsibility, helplessness for change in mothers with

  14. Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

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    Mezei Z

    2012-10-01

    Full Text Available Zsolt Mezei,1 Daniel Bereczki,1,2 Lilla Racz,1 Laszlo Csiba,1 Tunde Csepany11Department of Neurology, University of Debrecen, Debrecen, Hungary; 2Department of Neurology, Semmelweis University, Budapest, HungaryBackground: Decreased relapse rate and slower disease progression have been reported with long-term use of immunomodulatory treatments (IMTs, interferon beta or glatiramer acetate in relapsing–remitting multiple sclerosis. There are, however, patients who do not respond to such treatments, and they can be potential candidates for alternative therapeutic approaches.Objective: To identify clinical factors as possible predictors of poor long-term response.Methods: A 9-year prospective, continuous follow-up at a single center in Hungary to assess clinical efficacy of IMT.Results: In a patient group of 81 subjects with mean IMT duration of 54 ± 33 months, treatment efficacy expressed as annual relapse rate and change in clinical severity from baseline did not depend on the specific IMT (any of the interferon betas or glatiramer acetate, and on mono- or multifocal features of the initial appearance of the disease. Responders had shorter disease duration and milder clinical signs at the initiation of treatment. Relapse-rate reduction in the initial 2 years of treatment predicted clinical efficacy in subsequent years.Conclusion: Based on these observations, we suggest that a 2-year trial period is sufficient to decide on the efficacy of a specific IMT. For those with insufficient relapse reduction in the first 2 years of treatment, a different IMT or other therapeutic approaches should be recommended.Keywords: multiple sclerosis, immunomodulatory, EDSS, relapse, response

  15. Shiitake Culinary-Medicinal Mushroom, Lentinus edodes (Agaricomycetes): A Species with Antioxidant, Immunomodulatory, and Hepatoprotective Activities in Hypercholesterolemic Rats.

    Science.gov (United States)

    Nisar, Jaweria; Mustafa, Imtiaz; Anwar, Haseeb; Sohail, Muhammad Umar; Hussain, Ghulam; Ullah, Muhammad Irfan; Faisal, Muhammad Naeem; Bukhari, Shazia Anwer; Basit, Abdul

    2017-01-01

    Lentinus edodes is a culinary-medicinal mushroom that has an established history of use in Asian therapies. The mushroom offers well-documented beneficial health effects such as antihypercholesterolemic, antitumor, and antibacterial activities. In this study, dried powder of L. edodes fruiting bodies was used to evaluate immunomodulatory, hepatoprotective, and antioxidant effects in hypercholesterolemic rats. Albino rats (n = 24) were divided into 3 groups: the control (CON) group, the hypercholesterolemia-only group (HCG), and the L. edodes group (LEG). Hypercholesterolemia was induced in rats in the HCG and LEG by feeding cholesterol and cholic acid in a chow maintenance diet (CMD) for 24 days. The CON group was fed the CMD throughout the experiment. The HCG continued on the high-cholesterol diet without any L. edodes supplement. The LEG was fed the high-cholesterol diet supplemented with L. edodes for an additional 42 days. Various biological health biomarkers, such as total antioxidant capacity, total oxidant status, arylesterase, paraoxonase activity, and liver enzymes in serum were studied to evaluate antioxidant and hepatoprotective responses. Cell-mediated immunity was evaluated in each group through a delayed type of hypersensitivity reaction. The total oxidant status decreased significantly (P ≤ 0.05) after administration of L. edodes in the diet. The cell-mediated immune response significantly increased (P ≤ 0.05) in the LEG. The significant decrease in liver enzymes supports the hepatoprotective effect of L. edodes. In conclusion, the results show the immunomodulatory, hepatoprotective, and antioxidant activities of L. edodes supplementation in hypercholesterolemic rats.

  16. Ex vivo immunomodulatory effect of ethanolic extract of propolis during Celiac Disease: involvement of nitric oxide pathway.

    Science.gov (United States)

    Medjeber, Oussama; Touri, Kahina; Rafa, Hayet; Djeraba, Zineb; Belkhelfa, Mourad; Boutaleb, Amira Fatima; Arroul-Lammali, Amina; Belguendouz, Houda; Touil-Boukoffa, Chafia

    2018-03-07

    Celiac Disease (CeD) is a chronic immune-mediated enteropathy, in which dietary gluten induces an inflammatory reaction, predominantly in the duodenum. Propolis is a resinous hive product, collected by honeybees from various plant sources. Propolis is well-known for its anti-inflammatory, anti-oxidant and immunomodulatory effects, due to its major compounds, polyphenols and flavonoids. The aim of our study was to assess the ex vivo effect of ethanolic extract of propolis (EEP) upon the activity and expression of iNOS, along with IFN-γ and IL-10 production in Algerian Celiac patients. In this context, PBMCs isolated from peripheral blood of Celiac patients and healthy controls were cultured with different concentrations of EEP. NO production was measured using the Griess method, whereas quantitation of IFN-γ and IL-10 levels was performed by ELISA. Inducible nitric oxide synthase (iNOS) expression, NFκB and pSTAT-3 activity were analyzed by immunofluorescence assay. Our results showed that PBMCs from Celiac patients produced high levels of NO and IFN-γ compared with healthy controls (HC). Interestingly, EEP reduced significantly, NO and IFN-γ levels and significantly increased IL-10 levels at a concentration of 50 µg/mL. Importantly, EEP downmodulated the iNOS expression as well as the activity of NFκB and pSTAT-3 transcription factors. Altogether, our results highlight the immunomodulatory effect of propolis on NO pathway and on pro-inflammatory cytokines. Therefore, we suggest that propolis may constitute a potential candidate to modulate inflammation during Celiac Disease and has a potential therapeutic value.

  17. Antineoplastic and immunomodulatory effect of polyphenolic components of Achyranthes aspera (PCA) extract on urethane induced lung cancer in vivo.

    Science.gov (United States)

    Narayan, Chandradeo; Kumar, Arvind

    2014-01-01

    Polyphenolic compounds of Achyranthes aspera (PCA) extract is evaluated for anti-cancerous and cytokine based immunomodulatory effects. The PCA extract contains known components of phenolic acid and flavonoids such as mixture of quinic acid, chlorogenic acid, kaempferol, quercetin and chrysin along with many unknown components. PCA has been orally feed to urethane (ethyl carbamate) primed lung cancerous mice at a dosage of 100 mg/kg body weight for 30 consecutive days. 100 mg powder of A. aspera contains 2.4 mg phenolic acid and 1.1 mg flavonoid (2:1 ratio). Enhanced activities and expression of antioxidant enzymes GST, GR, CAT, SOD, while down regulated expression and activation of LDH enzymes in PCA feed urethane primed lung cancerous tissues as compared to PCA non-feed urethane primed lung cancerous tissues were observed. PCA feed urethane primed lung tissues showed down regulated expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α along with TFs, NF-κB and Stat3 while the expression of pro-apoptotic proteins Bax and p53 were enhanced in PCA feed urethane primed lung tissues. FTIR and CD spectroscopy data revealed that PCA resisted the urethane mediated conformational changes of DNA which is evident by the shift in guanine and thymine bands in FTIR from 1,708 to 1,711 cm(-1) and 1,675 to 1,671 cm(-1), respectively in PCA feed urethane primed lung cancerous tissues DNA in comparison to urethane primed lung cancerous tissues DNA. The present study suggests that PCA components have synergistic anti-cancerous and cytokine based immunomodulatory role and DNA conformation restoring effects. However, more research is required to show the effects of each component separately and in combination for effective therapeutic use to cure and prevent lung cancer including other cancers.

  18. The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells.

    Science.gov (United States)

    Pourgholaminejad, Arash; Aghdami, Nasser; Baharvand, Hossein; Moazzeni, Seyed Mohammad

    2016-09-01

    Mesenchymal stem cells (MSCs), as cells with potential clinical utilities, have demonstrated preferential incorporation into inflammation sites. Immunophenotype and immunomodulatory functions of MSCs could alter by inflamed-microenvironments due to the local pro-inflammatory cytokine milieu. A major cellular mediator with specific function in promoting inflammation and pathogenicity of autoimmunity are IL-17-producing T helper 17 (Th17) cells that polarize in inflamed sites in the presence of pro-inflammatory cytokines such as Interleukin-1β (IL-1β), IL-6 and IL-23. Since MSCs are promising candidate for cell-based therapeutic strategies in inflammatory and autoimmune diseases, Th17 cell polarizing factors may alter MSCs phenotype and function. In this study, human bone-marrow-derived MSCs (BM-MSC) and adipose tissue-derived MSCs (AD-MSC) were cultured with or without IL-1β, IL-6 and IL-23 as pro-inflammatory cytokines. The surface markers and their differentiation capacity were measured in cytokine-untreated and cytokine-treated MSCs. MSCs-mediated immunomodulation was analyzed by their regulatory effects on mixed lymphocyte reaction (MLR) and the level of IL-10, TGF-β, IL-4, IFN-γ and TNF-α production as immunomodulatory cytokines. Pro-inflammatory cytokines showed no effect on MSCs morphology, immunophenotype and co-stimulatory molecules except up-regulation of CD45. Adipogenic and osteogenic differentiation capacity increased in CD45+ MSCs. Moreover, cytokine-treated MSCs preserved the suppressive ability of allogeneic T cell proliferation and produced higher level of TGF-β and lower level of IL-4. We concluded pro-inflammatory cytokines up-regulate the efficacy of MSCs in cell-based therapy of degenerative, inflammatory and autoimmune disorders. Copyright © 2016. Published by Elsevier Ltd.

  19. In vitro bioassessment of the immunomodulatory activity of Saccharomyces cerevisiae components using bovine macrophages and Mycobacterium avium ssp. paratuberculosis.

    Science.gov (United States)

    Li, Z; Kang, H; You, Q; Ossa, F; Mead, P; Quinton, M; Karrow, N A

    2018-04-11

    The yeast Saccharomyces cerevisiae and its components are used for the prevention and treatment of enteric disease in different species; therefore, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). The objective of this study was to identify potential immunomodulatory S. cerevisiae components using a bovine macrophage cell line (BOMAC). The BOMAC phagocytic activity, reactive oxygen species production, and immune-related gene (IL6, IL10, IL12p40, IL13, IL23), transforming growth factor β, ARG1, CASP1, and inducible nitric oxide synthase expression were investigated when BOMAC were cocultured with cell wall components from 4 different strains (A, B, C, and D) and 2 forms of dead yeast from strain A. The BOMAC phagocytosis of mCherry-labeled MAP was concentration-dependently attenuated when BOMAC were cocultured with yeast components for 6 h. Each yeast derivative also induced a concentration-dependent increase in BOMAC reactive oxygen species production after a 6-h exposure. In addition, BOMAC mRNA expression of the immune-related genes was investigated after 6 and 24 h of exposure to yeast components. All yeast components were found to regulate the immunomodulatory genes of BOMAC; however, the response varied among components and over time. The in vitro bioassessment studies reported here suggest that dead yeast and its cell wall components may be useful for modulating macrophage function before or during MAP infection. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure

    International Nuclear Information System (INIS)

    Corsini, Emanuela; Codeca, Ilaria; Mangiaratti, Simona; Birindelli, Sarah; Minoia, Claudio; Turci, Roberta; Viviani, Barbara; Facchi, Alessandra; Vitelli, Nora; Lucchi, Laura; Galli, Corrado L.; Marinovich, Marina; Colosio, Claudio

    2007-01-01

    Propanil, 3,4-dichloropropionanilide, a commonly used herbicide, has been shown to induce effects on the mouse immune system. The aim of this study was to assess the immunotoxicity of propanil in occupationally exposed agricultural workers and to characterize its molecular mechanism of action. Seven agricultural workers intermittently exposed to propanil and 7 healthy matched controls entered the study. Data were collected through physical examination, and laboratory investigations addressed at the main serum, cellular, and functional immune parameters. The levels of exposure were assessed by determining the urine concentration of the major propanil metabolite, 3,4-dichloroaniline. The investigation of serum, cellular, and functional immune parameters suggested that propanil exposure results in a modest immunomodulatory effect, characterized by an increase in the plasma level of IgG 1 and in LPS-induced IL-6 release and, by a reduction in PHA-induced IL-10 and IFN release, associated with a reduced IFN/IL-4 ratio. As observed, following in vivo exposure, in vitro treatment of human peripheral blood leukocytes with propanil resulted in a dose-dependent reduction in PHA-induced IFN-gamma and IL-10 production, while LPS-induced TNF-α production was not affected indicating a direct effect of propanil on selected immune parameters. We demonstrated that propanil interfering with PHA-induced intracellular calcium increase modulated IL-10 and IFN-gamma transcription and translation, which indicates that propanil acts on early events triggered by PHA. Overall, our results suggest that human exposure to propanil has slight immunomodulatory effects, and point out that the inhibition of the PHA-induced intracellular calcium rise is an important target of propanil. These findings improve our understanding of the mechanism underlying propanil-induced immunotoxicity

  1. The length of a lantibiotic hinge region has profound influence on antimicrobial activity and host specificity

    Directory of Open Access Journals (Sweden)

    Liang eZhou

    2015-01-01

    Full Text Available Lantibiotics are ribosomally synthesized (methyllanthionine containing peptides which can efficiently inhibit the growth of Gram-positive bacteria. As lantibiotics kill bacteria efficiently and resistance to them is difficult to be obtained, they have the potential to be used in many applications, e.g. in pharmaceutical industry or food industry. Nisin can inhibit the growth of Gram-positive bacteria by binding to lipid II and by making pores in their membrane. The C-terminal part of nisin is known to play an important role during translocation over the membrane and forming pore complexes. However, as the thickness of bacterial membranes varies between different species and environmental conditions, this property could have an influence on the pore forming activity of nisin. To investigate this, the so-called hinge region of nisin (residues NMK was engineered to vary from one to six amino acid residues and specific activity against different indicators was compared. Antimicrobial activity in liquid culture assays showed that wild type nisin is most active, while truncation of the hinge region dramatically reduced the activity of the peptide. However, one or two amino acids extensions showed only slightly reduced activity against most indicator strains. Notably, some variants (+2, +1, -1, -2 exhibited higher antimicrobial activity than nisin in agar well diffusion assays against Lactococcus lactis MG1363, Listeria monocytogenes, Enterococcus faecalis VE14089, Bacillus sporothermodurans IC4 and Bacillus cereus 4153 at certain temperatures.

  2. Subtle variation in shade avoidance responses may have profound consequences for plant competitiveness.

    Science.gov (United States)

    Bongers, Franca J; Pierik, Ronald; Anten, Niels P R; Evers, Jochem B

    2017-12-21

    Although phenotypic plasticity has been shown to be beneficial for plant competitiveness for light, there is limited knowledge on how variation in these plastic responses plays a role in determining competitiveness. A combination of detailed plant experiments and functional-structural plant (FSP) modelling was used that captures the complex dynamic feedback between the changing plant phenotype and the within-canopy light environment in time and 3-D space. Leaf angle increase (hyponasty) and changes in petiole elongation rates in response to changes in the ratio between red and far-red light, two important shade avoidance responses in Arabidopsis thaliana growing in dense population stands, were chosen as a case study for plant plasticity. Measuring and implementing these responses into an FSP model allowed simulation of plant phenotype as an emergent property of the underlying growth and response mechanisms. Both the experimental and model results showed that substantial differences in competitiveness may arise between genotypes with only marginally different hyponasty or petiole elongation responses, due to the amplification of plant growth differences by small changes in plant phenotype. In addition, this study illustrated that strong competitive responses do not necessarily have to result in a tragedy of the commons; success in competition at the expense of community performance. Together, these findings indicate that selection pressure could probably have played a role in fine-tuning the sensitive shade avoidance responses found in plants. The model approach presented here provides a novel tool to analyse further how natural selection could have acted on the evolution of plastic responses.

  3. Cortical activation in profoundly deaf patients during cochlear implant stimulation demonstrated by H2(15)O PET

    International Nuclear Information System (INIS)

    Herzog, H.; Lamprecht, A.; Kuehn, A.R.; Roden, W.; Vosteen, K.H.; Feinendegen, L.E.

    1991-01-01

    Cochlear implants (CIs) are used to provide sensations of sound to profoundly deaf patients. The performance of the CI is assessed mainly by the subjective reports of patients. The aim of this study was to look for objective cortical responses to the stimulation of the CI. Two postlingually and two prelingually deaf patients were investigated by positron emission tomography (PET) using 15 O-labeled water (H 2 15 O) to determine the regional cerebral blood flow (rCBF). Instead of quantifying rCBF in absolute terms, it was estimated by referring the regional tissue concentration of H 2 15 O to the mean whole brain concentration. CI stimulation encoded from white noise and sequential words led to an increased rCBF in the primary and secondary (Wernicke) auditory cortex. Relative elevations of up to 33% were observed bilaterally, although they were higher contralateral to the CI. These results were obtained not only in the postlingually deaf patients but also in two patients who had never been able to hear. Thus, it could be demonstrated that PET measurements of cerebral H 2 15 O distribution yield objective responses of the central auditory system during electrical stimulation by CIs in profoundly deaf patients

  4. Immunomodulation properties of multi-species fermented milks.

    Science.gov (United States)

    Foligné, Benoît; Parayre, Sandrine; Cheddani, Redouane; Famelart, Marie-Hélène; Madec, Marie-Noëlle; Plé, Coline; Breton, Jérôme; Dewulf, Joëlle; Jan, Gwénaël; Deutsch, Stéphanie-Marie

    2016-02-01

    Dairy propionibacteria (PAB) are used as a ripening starter in combination with Lactic acid bacteria (LAB) for dairy products such as Swiss-type cheese. LAB and PAB have also been studied for their probiotic properties but little is still known about their individual and/or synergistic beneficial effects within dairy matrices. In the context of a rising incidence of Inflammatory Bowel Diseases, it has become crucial to evaluate the immunomodulatory potential of bacteria ingested in large numbers via dairy products. We therefore selected different strains and combinations of technological LAB and PAB. We determined their immunomodulatory potential by IL-10 and IL-12 induction, in human peripheral blood mononuclear cells, on either single or mixed cultures, grown on laboratory medium or directly in milk. Milk was fermented with selected anti-inflammatory strains of LAB or PAB/LAB mixed cultures and the resulting bacterial fractions were also evaluated for these properties, together with starter viability and optimum technological aspects. The most promising fermented milks were evaluated in the context of TNBS- or DSS-induced colitis in mice. The improvement in inflammatory parameters evidenced an alleviation of colitis symptoms as a result of fermented milk consumption. This effect was clearly strain-dependent and modulated by growth within a fermented dairy product. These findings offer new tools and perspectives for the development of immunomodulatory fermented dairy products for targeted populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Exploring the motor development of young children with possible severe to profound cognitive and motor developmental delay by means of a questionnaire

    NARCIS (Netherlands)

    Schalen, Gertruud Henrike; van der Putten, Annette; Maes, Bea; Vlaskamp, Carla

    Aim: Early motor stimulation may be valuable for children with profound intellectual and multiple disabilities (PIMD), however limited knowledge of their typical motor developmental trajectory may be currently restraining the efficacy and specificity of this intervention. Research on young children

  6. Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study.

    NARCIS (Netherlands)

    Boer, H.D. de; Driessen, J.J.; Marcus, M.A.; Kerkkamp, H.E.M.; Heeringa, M.; Klimek, M.

    2007-01-01

    BACKGROUND: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular

  7. The impact of visual impairment on the ability to perform activities of daily living for persons with severe/profound intellectual disability.

    Science.gov (United States)

    Dijkhuizen, Annemarie; Hilgenkamp, Thessa I M; Krijnen, Wim P; van der Schans, Cees P; Waninge, Aly

    2016-01-01

    The ability to perform activities of daily living (ADL) as a component of participation is one of the factors that contribute to quality of life. The ability to perform ADL for persons experiencing severe/profound intellectual disability (ID) may be reduced due to their cognitive and physical capacities. However, until recently, the impact of the significantly prevalent visual impairments on the performance of activities of daily living has not yet been revealed within this group. The purpose of this prospective cross-sectional study was to investigate the impact of visual impairment on the performance of activities of daily living for persons with a severe/profound intellectual disability. The Barthel Index (BI) and Comfortable Walking Speed (CWS) were used to measure the ability of performing activities of daily living (ADL) in 240 persons with severe/profound ID and having Gross Motor Functioning Classification System (GMFCS) levels I, II or III; this included 120 persons with visual impairment. The impact of visual impairment on ADL was analyzed with linear regression. The results of the study demonstrated that visual impairment slightly affects the ability of performing activities of daily living (BI) for persons experiencing a severe/profound intellectual disability. GMFCS Levels II or III, profound ID level, and visual impairment each have the effect of lowering BI scores. GMFCS Levels II or III, and profound ID level each have the effect of increasing CWS scores, which indicates a lower walking speed. A main effect of visual impairment is present on CWS, but our results do show a substantive interaction effect between GMFCS level III and visual impairment on Comfortable Walking Speed in persons with a severe/profound intellectual disability. Visual impairment has a slight effect on ability to perform ADL in persons experiencing severe/profound ID. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Efforts to increase social contact in persons with profound intellectual and multiple disabilities: Analysing individual support plans in the Netherlands.

    Science.gov (United States)

    Kamstra, Aafke; van der Putten, Annette Aj; Vlaskamp, Carla

    2017-06-01

    Most people with profound intellectual and multiple disabilities (PIMD) have limited social contact and it is unclear what is done to maintain or increase these contacts. Individual support planning (ISP) can be used in the systematic enhancement of social contacts. This study analyses the content of ISPs with respect to the social contacts of people with PIMD. ISPs for 60 persons with PIMD in the Netherlands were inductively coded and illustrated with quotations. It turned out that every ISP contained information about social contacts. Of all the quotations extracted, 71.2% were about current conditions, 6.2% were about the future and less than 1% concerned actual goals. The social contacts of people with PIMD are mentioned in their ISPs, but this is rarely translated into goals. The results of the current study suggest that attention should be paid to ensuring that professionals understand the importance of social contacts and their application in practice.

  9. An ecological method for the sampling of nonverbal signalling behaviours of young children with profound and multiple learning disabilities (PMLD).

    Science.gov (United States)

    Atkin, Keith; Lorch, Marjorie Perlman

    2016-08-01

    Profound and multiple learning disabilities (PMLD) are a complex range of disabilities that affect the general health and well-being of the individual and their capacity to interact and learn. We developed a new methodology to capture the non-symbolic signalling behaviours of children with PMLD within the context of a face-to-face interaction with a caregiver to provide analysis at a micro-level of descriptive detail incorporating the use of the ELAN digital video software. The signalling behaviours of participants in a natural, everyday interaction can be better understood with the use of this innovation in methodology, which is predicated on the ecology of communication. Recognition of the developmental ability of the participants is an integral factor within that ecology. The method presented establishes an advanced account of the modalities through which a child affected by PMLD is able to communicate.

  10. A Case of Profound Soft Tissue Infection of Lower Limb Contained Maggots after IV Abuse of Iranian

    Directory of Open Access Journals (Sweden)

    Majid Heidary

    2016-07-01

    Full Text Available Background: Infections include soft tissue infections are notable reason for hospital admission among IDUs, owing to unsterile injection techniques and equipment, contamination of drugs with organisms, and poor hygiene. In present case report a patient with profound limb infection is introduced. Case: A 32 years old man was transferred to the emergency department. He was IDU with Iranian for 3 years. Gangrenous deformity of left lower extremity below the knee was seen. Live maggots were moving around the limb freely. The patient underwent before knee amputation (BKA to remove the infected tissues of the limb. Conclusion: In order to evaluate and treat the serious infectious disease problems, drug abuse treatment programs will need to develop appropriate procedures. It is important that physicians, nurses, and other health care providers become better educated about drug abuse. Workers in drug abuse treatment should be well informed about infectious diseases and other complications of drug abuse.

  11. Apple cider vinegar boosted immunomodulatory and health promoting effects of Lactobacillus casei in common carp (Cyprinus carpio).

    Science.gov (United States)

    Safari, Roghieh; Hoseinifar, Seyed Hossein; Nejadmoghadam, Shabnam; Khalili, Mohsen

    2017-08-01

    The present study was performed to investigate the immunomodulatory and health promoting effects of combined or singular administration of apple cider vinegar (ACV) and Lactobacillus casei in common carp (Cyprinus carpio) diet. An 8-week feeding trial was designed with following treatments: Control (basal diet), Pro (contains 10 7  CFU g -1 L. casei), LACV (contains 1% ACV), HACV (contains 2% ACV), Pro + LACV (contains 10 7  CFU g -1 L. casei plus 1% ACV) and Pro + HACV (contains 10 7  CFU g -1 L. casei plus 2% ACV). Evaluation of skin mucus revealed notable increase of total Ig level and lysozyme activity in Pro + LACV and Pro + HACV treatments compared other groups (P < 0.05). Similarly, serum total Ig and lysozyme activity in HACV, Pro + LACV and Pro + HACV fed carps was remarkably higher than other groups (P < 0.05). However, regarding serum alternative complement (ACH50) activity significant difference was observed just between Pro + HACV and control treatment (P < 0.05). The highest expression of immune related (LYZ, TNF-alpha, IL1b, IL8) and antioxidant enzymes genes (GSR, GST) were observed in carps fed Pro + HACV and Pro + LACV. The expression of GH gene expression in Pro, LACV and HACV treatments was significantly higher than those in control group (P < 0.05). The highest expression level of GH and IGF1 was observed in fish fed combined Pro and ACV (P < 0.05). These results indicated that co-administration of ACV boosted immunomodulatory and health promoting effects of L. casei and can be considered as a promising immunostimulants in early stage of common carp culture. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. n Vitro Immunomodulatory Effect of R10 Fraction of Garlic on Viability and Production of TNF-? in CD8+ T Cells

    OpenAIRE

    T. Ghazanfari; H. Rashidi; Sh. Jalaei; P. Alijani

    2014-01-01

    Introduction & Objective: -cells, especially CD8+ T lymphocytes are the most important cells in anti-tumor response. Previously R10 fraction of garlic extract was reported as an immuno-modulator which induced an effective cellular immunity and Th1 responses. In this study the in vitro immunomodulatory effect of R10 on CD8+ T cells viability and production of TNF-? were evaluated. Materials & Methods: In this experimental study, using monoclonal antibodies attached to magnetic beads with isola...

  13. Evaluation of Antioxidant, Immunomodulatory, and Cytotoxic Action of Fractions from Eugenia uniflora L. and Eugenia malaccensis L.: Correlation with Polyphenol and Flavanoid Content

    OpenAIRE

    Figueir?a, Evellyne de Oliveira; Nascimento da Silva, Lu?s Cl?udio; de Melo, Cristiane Moutinho Lagos; Neves, Juliana Kelle de Andrade Lemoine; da Silva, Nic?cio Henrique; Pereira, Val?ria R?go Alves; Correia, Maria Tereza dos Santos

    2013-01-01

    An increasing number of biological activities presented by medicinal plants has been investigated over the years, and they are used in the search for new substances with lower side effects. Eugenia uniflora L. and Eugenia malaccensis L. (Myrtaceae) have many folk uses in various countries. This current study was designed to quantify the polyphenols and flavonoids contents and evaluate the immunomodulatory, antioxidant, and cytotoxic potentials of fractions from E. uniflora L. and E. malaccens...

  14. Immunomodulatory activity of extracts from Cordia superba Cham. and Cordia rufescens A. DC. (Boraginaceae), plant species native from Brazilian Semi-arid

    OpenAIRE

    Costa,José Fernando Oliveira; David,Juceni P. L.; David,Jorge M.; Giulietti,Ana M.; Queiroz,Luciano P.; Santos,Ricardo R.; Soares,Milena Botelho P.

    2008-01-01

    The family Boraginaceae is widely distributed in Brazil and in the Northeastern region some species are popularly used to treat symptoms of rheumatism, painful menstruation and dyspepsia. In this work we studied Cordia superba Cham. and C. rufescens A. DC., native from Brazilian Semi-arid region, in order to investigate their immunomodulatory activity. Six extracts were prepared from aerial parts of C. superba and C. rufescens. The cytotoxicity was evaluated using splenocytes from BALB/c mice...

  15. Comparisons of phenotype and immunomodulatory capacity among rhesus bone-marrow-derived mesenchymal stem/stromal cells, multipotent adult progenitor cells, and dermal fibroblasts

    Science.gov (United States)

    Wang, Qi; Clarkson, Christina; Graham, Melanie; Donahue, Robert; Hering, Bernhard J.; Verfaillie, Catherine M.; Bansal-Pakala, Pratima; O'Brien, Timothy D.

    2015-01-01

    Background Potent immunomodulatory effects have been reported for mesenchymal stem/stromal cells (MSCs), multipotent adult progenitor cells (MAPCs), and fibroblasts. However, side-by-side comparisons of these cells specifically regarding immunophenotype, gene expression, and suppression of proliferation of CD4+ and CD8+ lymphocyte populations have not been reported. Methods We developed MAPC and MSC lines from rhesus macaque bone marrow and fibroblast cell lines from rhesus dermis and assessed phenotypes based upon differentiation potential, flow cytometric analysis of immunophenotype, and quantitative RT-PCR analysis of gene expression. Using allogeneic lymphocyte proliferation assays, we compared the in vitro immunomodulatory potency of each cell type. Results and Conclusions Extensive phenotypic similarities exist among each cell type, although immunosuppressive potencies are distinct. MAPCs are most potent, and fibroblasts are the least potent cell type. All three cell types demonstrated immunomodulatory capacity such that each may have potential therapeutic applications such as in organ transplantation, where reduced local immune response is desirable. PMID:24825538

  16. Immunomodulatory Activity of Ganoderma atrum Polysaccharide on Purified T Lymphocytes through Ca2+/CaN and Mitogen-Activated Protein Kinase Pathway Based on RNA Sequencing.

    Science.gov (United States)

    Xiang, Quan-Dan; Yu, Qiang; Wang, Hui; Zhao, Ming-Ming; Liu, Shi-Yu; Nie, Shao-Ping; Xie, Ming-Yong

    2017-07-05

    Our previous study has demonstrated that Ganoderma atrum polysaccharide (PSG-1) has immunomodulatory activity on spleen lymphocytes. However, how PSG-1 exerts its effect on purified lymphocytes is still obscure. Thus, this study aimed to investigate the immunomodulatory activity of PSG-1 on purified T lymphocytes and further elucidate the underlying mechanism based on RNA sequencing (RNA-seq). Our results showed that PSG-1 promoted T lymphocytes proliferation and increased the production of IL-2, IFN-γ, and IL-12. Meanwhile, RNA-seq analysis found 394 differentially expressed genes. KEGG pathway analysis identified 20 significant canonical pathways and seven biological functions. Furthermore, PSG-1 elevated intracellular Ca 2+ concentration and calcineurin (CaN) activity and raised the p-ERK, p-JNK, and p-p38 expression levels. T lymphocytes proliferation and the production of IL-2, IFN-γ, and IL-12 were decreased by the inhibitors of calcium channel and mitogen-activated protein kinases (MAPKs). These results indicated that PSG-1 possesses immunomodulatory activity on purified T lymphocytes, in which Ca 2+ /CaN and MAPK pathways play essential roles.

  17. Studies on Antimicrobial and Immunomodulatory Effects of Hot Aqueous Extract of Acacia nilotica L. Leaves against Common Veterinary Pathogens

    Directory of Open Access Journals (Sweden)

    Arvind Kumar Sharma

    2014-01-01

    Full Text Available Acacia nilotica is a plant species that is almost ubiquitously found in different parts of the world. Various preparations of it have been advocated in folk medicine for the treatment of tuberculosis, leprosy, smallpox, dysentery, cough, ophthalmia, toothache, skin cancer as astringent, antispasmodic, and aphrodisiac since immemorial times. The present study investigates the antibacterial, antifungal, antiviral, and immunomodulatory potential of hot aqueous extract (HAE of Acacia nilotica leaves. On dry matter basis, the filtered HAE had a good extraction ratio (33.46% and was found to have carbohydrates, glycosides, phytosterols, phenolic compounds, saponins, and flavonoids as major constituents. HAE produced dose dependent zone of inhibition against Klebsiella pneumoniae, Pseudomonas aeruginosa, E. coli, Bacillus cereus, Staphylococcus aureus, and Streptococcus uberis and fungal pathogens Aspergillus niger and Aspergillus fumigates; however, no antiviral activity was recorded against IBR virus. HAE of A. nilotica revealed both proliferative and inhibitory effects on the rat splenocytes and IL-10 release depending on the dose. Detailed studies involving wide spectrum of bacterial, fungal, and viral species are required to prove or know the exact status of each constituents of the plant extract.

  18. Immunomodulatory role of interleukin-10 in visceral leishmaniasis: defective activation of protein kinase C-mediated signal transduction events.

    Science.gov (United States)

    Bhattacharyya, S; Ghosh, S; Jhonson, P L; Bhattacharya, S K; Majumdar, S

    2001-03-01

    Leishmania donovani, an intracellular protozoan parasite, challenges host defense mechanisms by impairing the signal transduction of macrophages. In this study we investigated whether interleukin-10 (IL-10)-mediated alteration of signaling events in a murine model of visceral leishmaniasis is associated with macrophage deactivation. Primary in vitro cultures of macrophages infected with leishmanial parasites markedly elevated the endogenous release of IL-10. Treatment with either L. donovani or recombinant IL-10 (rIL-10) inhibited both the activity and expression of the Ca2+-dependent protein kinase C (PKC) isoform. However, preincubation with neutralizing anti-IL-10 monoclonal antibody (MAb) restored the PKC activity in the parasitized macrophage. Furthermore, we observed that coincubation of macrophages with rIL-10 and L. donovani increased the intracellular parasite burden, which was abrogated by anti-IL-10 MAb. Consistent with these observations, generation of superoxide (O2-) and nitric oxide and the release of murine tumor necrosis factor-alpha were attenuated in response to L. donovani or rIL-10 treatment. On the other hand, preincubation of the infected macrophages with neutralizing anti-IL-10 MAb significantly blocked the inhibition of nitric oxide and murine tumor necrosis factor-alpha release by the infected macrophages. These findings imply that infection with L. donovani induces endogenous secretion of murine IL-10, which in turn facilitates the intracellular survival of the protozoan and orchestrates several immunomodulatory roles via selective impairment of PKC-mediated signal transduction.

  19. Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms Formed by Pathogens Isolated from Cystic Fibrosis Patients

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    César de la Fuente-Núñez

    2014-10-01

    Full Text Available Cystic fibrosis (CF patients often acquire chronic respiratory tract infections due to Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc species. In the CF lung, these bacteria grow as multicellular aggregates termed biofilms. Biofilms demonstrate increased (adaptive resistance to conventional antibiotics, and there are currently no available biofilm-specific therapies. Using plastic adherent, hydroxyapatite and flow cell biofilm models coupled with confocal and scanning electron microscopy, it was demonstrated that an anti-biofilm peptide 1018 prevented biofilm formation, eradicated mature biofilms and killed biofilms formed by a wide range of P. aeruginosa and B. cenocepacia clinical isolates. New peptide derivatives were designed that, compared to their parent peptide 1018, showed similar or decreased anti-biofilm activity against P. aeruginosa biofilms, but increased activity against biofilms formed by the Gram-positive bacterium methicillin resistant Staphylococcus aureus. In addition, some of these new peptide derivatives retained the immunomodulatory activity of 1018 since they induced the production of the chemokine monocyte chemotactic protein-1 (MCP-1 and suppressed lipopolysaccharide-mediated tumor necrosis factor-α (TNF-α production by human peripheral blood mononuclear cells (PBMC and were non-toxic towards these cells. Peptide 1018 and its derivatives provide promising leads for the treatment of chronic biofilm infections and hyperinflammatory lung disease in CF patients.

  20. Immunomodulatory Role of Ocimum gratissimum and Ascorbic Acid against Nicotine-Induced Murine Peritoneal Macrophages In Vitro

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    Santanu Kar Mahapatra

    2011-01-01

    Full Text Available The aim of this present study was to evaluate the immune functions and immune responses in nicotine-induced (10 mM macrophages and concurrently establish the immunomodulatory role of aqueous extract of Ocimum gratissimum (Ae-Og and ascorbic acid. In this study, nitrite generations and some phenotype functions by macrophages were studied. Beside that, release of Th1 cytokines (TNF-α, IL-12 and Th2 cytokines (IL-10, TGF-β was measured by ELISA, and the expression of these cytokines at mRNA level was analyzed by real-time PCR. Ae-Og, at a dose of 10 μg/mL, significantly reduced the nicotine-induced NO generation and iNOSII expression. Similar kinds of response were observed with supplementation of ascorbic acid (0.01 mM. The administration of Ae-Og and ascorbic acid increased the decreased adherence, chemotaxis, phagocytosis, and intracellular killing of bacteria in nicotine-treated macrophages. Ae-Og and ascorbic acid were found to protect the murine peritoneal macrophages through downregulation of Th1 cytokines in nicotine-treated macrophages with concurrent activation of Th2 responses. These findings strongly enhanced our understanding of the molecular mechanism leading to nicotine-induced suppression of immune functions and provide additional rationale for application of anti-inflammatory therapeutic approaches by O. gratissimum and ascorbic acid for different inflammatory disease prevention and treatment during nicotine toxicity.

  1. Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity.

    Science.gov (United States)

    Eichner, Ruth; Heider, Michael; Fernández-Sáiz, Vanesa; van Bebber, Frauke; Garz, Anne-Kathrin; Lemeer, Simone; Rudelius, Martina; Targosz, Bianca-Sabrina; Jacobs, Laura; Knorn, Anna-Maria; Slawska, Jolanta; Platzbecker, Uwe; Germing, Ulrich; Langer, Christian; Knop, Stefan; Einsele, Herrmann; Peschel, Christian; Haass, Christian; Keller, Ulrich; Schmid, Bettina; Götze, Katharina S; Kuster, Bernhard; Bassermann, Florian

    2016-07-01

    Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin ligase complex, is the primary target by which IMiDs mediate anticancer and teratogenic effects. Here we identify a ubiquitin-independent physiological chaperone-like function of CRBN that promotes maturation of the basigin (BSG; also known as CD147) and solute carrier family 16 member 1 (SLC16A1; also known as MCT1) proteins. This process allows for the formation and activation of the CD147-MCT1 transmembrane complex, which promotes various biological functions, including angiogenesis, proliferation, invasion and lactate export. We found that IMiDs outcompete CRBN for binding to CD147 and MCT1, leading to destabilization of the CD147-MCT1 complex. Accordingly, IMiD-sensitive MM cells lose CD147 and MCT1 expression after being exposed to IMiDs, whereas IMiD-resistant cells retain their expression. Furthermore, del(5q) MDS cells have elevated CD147 expression, which is attenuated after IMiD treatment. Finally, we show that BSG (CD147) knockdown phenocopies the teratogenic effects of thalidomide exposure in zebrafish. These findings provide a common mechanistic framework to explain both the teratogenic and pleiotropic antitumor effects of IMiDs.

  2. Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM) on Streptozotocin-Induced Diabetic Mice.

    Science.gov (United States)

    Kim, Jong-Jin; Choi, Jina; Lee, Mi-Kyung; Kang, Kyung-Yun; Paik, Man-Jeong; Jo, Sung-Kee; Jung, Uhee; Park, Hae-Ran; Yee, Sung-Tae

    2014-01-01

    Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia japonica Miyabe) was developed to protect immune, hematopoietic, and self-renewal tissues against radiation. This study determined whether or not HemoHIM could alter hyperglycemia and the immune response in diabetic mice. Both nondiabetic and diabetic mice were orally administered HemoHIM (100 mg/kg) once a day for 4 weeks. Diabetes was induced by single injection of streptozotocin (STZ, 200 mg/kg, i.p.). In diabetic mice, HemoHIM effectively improved hyperglycemia and glucose tolerance compared to the diabetic control group as well as elevated plasma insulin levels with preservation of insulin staining in pancreatic β-cells. HemoHIM treatment restored thymus weight, white blood cells, lymphocyte numbers, and splenic lymphocyte populations (CD4(+) T and CD8(+) T), which were reduced in diabetic mice, as well as IFN-γ production in response to Con A stimulation. These results indicate that HemoHIM may have potential as a glucose-lowering and immunomodulatory agent by enhancing the immune function of pancreatic β-cells in STZ-induced diabetic mice.

  3. Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM on Streptozotocin-Induced Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Jong-Jin Kim

    2014-01-01

    Full Text Available HemoHIM (a new herbal preparation of three edible herbs: Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia japonica Miyabe was developed to protect immune, hematopoietic, and self-renewal tissues against radiation. This study determined whether or not HemoHIM could alter hyperglycemia and the immune response in diabetic mice. Both nondiabetic and diabetic mice were orally administered HemoHIM (100 mg/kg once a day for 4 weeks. Diabetes was induced by single injection of streptozotocin (STZ, 200 mg/kg, i.p.. In diabetic mice, HemoHIM effectively improved hyperglycemia and glucose tolerance compared to the diabetic control group as well as elevated plasma insulin levels with preservation of insulin staining in pancreatic β-cells. HemoHIM treatment restored thymus weight, white blood cells, lymphocyte numbers, and splenic lymphocyte populations (CD4+ T and CD8+ T, which were reduced in diabetic mice, as well as IFN-γ production in response to Con A stimulation. These results indicate that HemoHIM may have potential as a glucose-lowering and immunomodulatory agent by enhancing the immune function of pancreatic β-cells in STZ-induced diabetic mice.

  4. Immunomodulatory Role of an Ayurvedic Formulation on Imbalanced Immunometabolics during Inflammatory Responses of Obesity and Prediabetic Disease

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    Kamiya Tikoo

    2013-01-01

    Full Text Available Kal-1 is a polyherbal decoction of seven different natural ingredients, traditionally used in controlling sugar levels, inflammatory conditions particularly regulating metabolic and immunoinflammatory balance which are the major factors involved in obesity and related diseases. In the present study, we aimed to investigate the effect of Kal-1 (an abbreviation derived from the procuring source on diet-induced obesity and type II diabetes using C57BL/6J mice as a model. The present study was performed with two experimental groups involving obese and prediabetic mice as study animals. In one, the mice were fed on high-fat with increased sucrose diet, and different amounts (5, 20, and 75 μL of Kal-1 were administered with monitoring of disease progression over a period of 21 weeks whereas in the second group the mice were first put on the same diet for 21 weeks and then treated with the same amounts of Kal-1. A significant reduction in body weight, fat pads, fasting blood glucose levels, insulin levels, biochemical parameters, immunological parameters, and an array of pro- and anticytokines was observed in obese and diabetic mice plus Kal-1 than control (lean mice fed on normal diet. In conclusion, Kal-1 has immunomodulatory potential for diet-induced obesity and associated metabolic disorders.

  5. Pyrosequencing Analysis Reveals Changes in Intestinal Microbiota of Healthy Adults Who Received a Daily Dose of Immunomodulatory Probiotic Strains

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    Julio Plaza-Díaz

    2015-05-01

    Full Text Available The colon microbiota plays a crucial role in human gastrointestinal health. Current attempts to manipulate the colon microbiota composition are aimed at finding remedies for various diseases. We have recently described the immunomodulatory effects of three probiotic strains (Lactobacillus rhamnosus CNCM I-4036, Lactobacillus paracasei CNCM I-4034, and Bifidobacterium breve CNCM I-4035. The goal of the present study was to analyze the compositions of the fecal microbiota of healthy adults who received one of these strains using high-throughput 16S ribosomal RNA gene sequencing. Bacteroides was the most abundant genus in the groups that received L. rhamnosus CNCM I-4036 or L. paracasei CNCM I-4034. The Shannon indices were significantly increased in these two groups. Our results also revealed a significant increase in the Lactobacillus genus after the intervention with L. rhamnosus CNCM I-4036. The initially different colon microbiota became homogeneous in the subjects who received L. rhamnosus CNCM I-4036. While some orders that were initially present disappeared after the administration of L. rhamnosus CNCM I-4036, other orders, such as Sphingobacteriales, Nitrospirales, Desulfobacterales, Thiotrichales, and Synergistetes, were detected after the intervention. In summary, our results show that the intake of these three bacterial strains induced changes in the colon microbiota.

  6. Lymphocyte Glucose and Glutamine Metabolism as Targets of the Anti-Inflammatory and Immunomodulatory Effects of Exercise

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    Frederick Wasinski

    2014-01-01

    Full Text Available Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways.

  7. Comparison of in vivo immunomodulatory effects of 5-hydroxymethylfurfural and 5, 5'-oxydimethylenebis (2-furfural).

    Science.gov (United States)

    Lin, Ni; Liu, Tiantian; Lin, Lin; Lin, Sheng; Zang, Qingce; He, Jiuming; Abliz, Zeper; Li, Chao; Wang, Aiping; Jin, Hongtao

    2016-11-01

    The standard of 5-Hydroxymethylfurfural (5-HMF) existed in dextrose injection as an inevitable by-product during high-temperature setrilization has been included in pharmacopoeias considering its hazardous effects on human health. We found that the concentrations of 5-HMF in some traditional Chinese medicine injections (TCMIs) far exceeded its limit in dextrose injection. Besides, we detected 5, 5'-Oxydimethylenebis (2-furfural) (OMBF) in those TCMIs containing high concentrations of 5-HMF. We investigated the in vivo immunomodulatory effects of 5-HMF and OMBF at three dose levels using the reporter antigen popliteal lymph node assay (RA-PLNA), which allows the straightforward examination and mechanistic study of immunotoxicity of low molecular weight compounds. We found that 5-HMF increased the production of IgG 2a and IFN-γ when co-injected with TNP-OVA, indicating its capability of providing a co-stimulatory signal to evoke a typical type-1 immune response. Compared with the 5-HMF, OMBF elevated the production of IgG 1 , IgG 2 , IL-4 and IFN-γ in response to both reporter antigens, suggesting that OMBF can act as a neo-antigen or neo-epitope to elicit a mixed type-1 and type-2 immune response. It indicates that both 5-HMF and OMBF have immunosensitizing potential with different mechanisms, and exposure to 5-HMF and OMBF may represent a safety concern for humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Unusual immuno-modulatory triterpene-caffeates in the skins of russeted varieties of apples and pears.

    Science.gov (United States)

    Andre, Christelle M; Larsen, Lesley; Burgess, Elaine J; Jensen, Dwayne J; Cooney, Janine M; Evers, Danièle; Zhang, Jingli; Perry, Nigel B; Laing, William A

    2013-03-20

    Three triterpene-caffeates have been isolated from skins of a russeted apple cultivar "Merton Russet" and identified by LC-MS and NMR as betulinic acid-3-cis-caffeate, betulinic acid-3-trans-caffeate, and oleanolic acid-3-trans-caffeate. Betulinic acid-3-trans-caffeate and oleanolic acid-3-trans-caffeate were also found in russeted pear skins. These compounds have not been previously reported in apples or pears, or in any other foods. Their presence was related to suberized tissue as they were only found in russet portions of the partially russeted apple cultivar "Cox's Orange Pippin" and were not detected in the waxy apple cultivar "Royal Gala". High concentrations of betulinic acid-3-trans-caffeate were found in the bark of both "Merton Russet" and "Royal Gala" trees. The three triterpene-caffeates showed anti-inflammatory activity in vitro, inhibiting NF-κB activation with IC50's of 6-9 μM. Betulinic acid-3-trans-caffeate, the predominant compound in the apples, was immuno-modulatory at around 10 μM in the in vitro and ex vivo bioassays, boosting production of the pro-inflammatory cytokine TNFα in cells stimulated with bacterial lipopolysaccharides.

  9. Novel long-chain compounds with both immunomodulatory and MenA inhibitory activities against Staphylococcus aureus and its biofilm.

    Science.gov (United States)

    Choi, Seoung-Ryoung; Frandsen, Joel; Narayanasamy, Prabagaran

    2017-01-10

    Menaquinone (MK) biosynthesis pathway is a potential target for evaluating antimicrobials in gram-positive bacteria. Here, 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) was targeted to reduce methicillin-resistant Staphylococcus aureus (MRSA) growth. MenA inhibiting, long chain-based compounds were designed, synthesized and evaluated against MRSA and menaquinone utilizing bacteria in aerobic conditions. The results showed that these bacteria were susceptible to most of the compounds. Menaquinone (MK-4) supplementation rescued MRSA growth, suggesting these compounds inhibit MK biosynthesis. 3a and 7c exhibited promising inhibitory activities with MICs ranging 1-8 μg/mL against MRSA strains. The compounds did not facilitate small colony variant formation. These compounds also inhibited the biofilm growth by MRSA at high concentration. Compounds 3a, 6b and 7c displayed a promising extracellular bactericidal activity against MRSA at concentrations equal to and four-fold less than their respective MICs. We also observed cytokines released from THP-1 macrophages treated with compounds 3a, 6b and 7c and found decreases in TNF-α and IL-6 release and increase in IL-1β. These data provide evidence that MenA inhibitors act as TNF-α and IL-6 inhibitors, raising the potential for development and application of these compounds as potential immunomodulatory agents.

  10. Peripherally Generated Foxp3+ Regulatory T Cells Mediate the Immunomodulatory Effects of IVIg in Allergic Airways Disease.

    Science.gov (United States)

    Massoud, Amir H; Kaufman, Gabriel N; Xue, Di; Béland, Marianne; Dembele, Marieme; Piccirillo, Ciriaco A; Mourad, Walid; Mazer, Bruce D

    2017-04-01

    IVIg is widely used as an immunomodulatory therapy. We have recently demonstrated that IVIg protects against airway hyperresponsiveness (AHR) and inflammation in mouse models of allergic airways disease (AAD), associated with induction of Foxp3 + regulatory T cells (Treg). Using mice carrying a DTR/EGFP transgene under the control of the Foxp3 promoter (DEREG mice), we demonstrate in this study that IVIg generates a de novo population of peripheral Treg (pTreg) in the absence of endogenous Treg. IVIg-generated pTreg were sufficient for inhibition of OVA-induced AHR in an Ag-driven murine model of AAD. In the absence of endogenous Treg, IVIg failed to confer protection against AHR and airway inflammation. Adoptive transfer of purified IVIg-generated pTreg prior to Ag challenge effectively prevented airway inflammation and AHR in an Ag-specific manner. Microarray gene expression profiling of IVIg-generated pTreg revealed upregulation of genes associated with cell cycle, chromatin, cytoskeleton/motility, immunity, and apoptosis. These data demonstrate the importance of Treg in regulating AAD and show that IVIg-generated pTreg are necessary and sufficient for inhibition of allergen-induced AAD. The ability of IVIg to generate pure populations of highly Ag-specific pTreg represents a new avenue to study pTreg, the cross-talk between humoral and cellular immunity, and regulation of the inflammatory response to Ags. Copyright © 2017 by The American Association of Immunologists, Inc.

  11. Evaluation of antitumor, immunomodulatory and free radical scavenging effects of a new herbal prescription seaweed complex preparation

    Science.gov (United States)

    Liu, Xin; Shao, Changlun; Kong, Wenwen; Fang, Yuchun; Wang, Changyun

    2013-09-01

    Seaweed Complex Preparation (SCP) is a clinical traditional Chinese medicine preparation which is composed of seven traditional Chinese herbs, and it has been used for treatment of lung cancer, liver cancer and digestive cancer. However, little information is available about the pharmacodynamic basis. The antitumor, immunomodulatory and free radical scavenging effects of SCP were evaluated in this study. Transplanted tumor in vivo method was used to determine the antitumor effect. The effects on splenocyte proliferation and phagocytosis of macrophages in tumor-bearing mice were measured by the MTT method and the phagocytizing cock red blood cell (CRBC) method respectively. The scavenging activities of SCP on DPPH and hydroxyl radicals in vitro were investigated. It was found that the medium-dose and high-dose of SCP could significantly inhibit the growth of transplanted hepatic tumor of murine hepatocarcinoma cell line H22, and promote proliferation of splenocytes and phagocytosis of macrophages. SCP possessed noticeable scavenging activities on DPPH and hydroxyl radicals. The antitumor effects of SCP might be achieved by improving immune system and scavenging free radicals, which is in accordance with the viewpoint of traditional Chinese medicine in promoting the body resistance and eliminating pathogenic factors for cancer treatment.

  12. Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate Pathogenic Skin Inflammation in Mice.

    Science.gov (United States)

    Lee, Hyun Gyu; Cho, Nam-Chul; Jeong, Ae Jin; Li, Yu-Chen; Rhie, Sung-Ja; Choi, Jung Sook; Lee, Kwang-Ho; Kim, Youngsoo; Kim, Yong-Nyun; Kim, Myoung-Hwan; Pae, Ae Nim; Ye, Sang-Kyu; Kim, Byung-Hak

    2016-01-01

    T-cell-mediated immune responses play an important role in body protection. However, aberrantly activated immune responses are responsible for inflammatory and autoimmune diseases. The regulation of pathologic immune responses may be a potential therapeutic strategy for the treatment of these diseases. Despite that multiple pharmacologic properties of benzoxathiole derivatives have been defined, the molecular mechanisms underlying these properties remain to be clarified. Here, we demonstrated the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) regulated immune responses and ameliorated experimentally induced inflammatory skin diseases both in vitro and in vivo. BOT-4-one inhibited the differentiation of CD4(+) T-cell subsets by regulating the expression and production of T-cell lineage-specific master transcription factors and cytokines and activating the signal transducer and activator of transcription proteins. In addition, BOT-4-one inhibited TCR-mediated Akt and NF-κB signaling. Topical application of BOT-4-one ameliorated experimentally induced inflammatory skin diseases in mice models such as 2,4,6-trinitrochlorobenzene-induced contact and atopic dermatitis and IL-23-induced psoriasis-like skin inflammation. Our study demonstrated that BOT-4-one ameliorates inflammatory skin diseases by suppressing the pathogenic CD4(+) T cell differentiation and overall immune responses. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action

    International Nuclear Information System (INIS)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger; Stein, Jürgen; Fürst, Robert; Steinhilber, Dieter; Ulrich-Rückert, Sandra

    2015-01-01

    (Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC 50 values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G 2 /M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like PDEs, SIRT1

  14. Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Stein, Jürgen [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Department of Internal Medicine, Sachsenhausen Hospital, Frankfurt am Main (Germany); Fürst, Robert [Institute of Pharmaceutical Biology, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Steinhilber, Dieter [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Ulrich-Rückert, Sandra, E-mail: sandra.ulrich@em.uni-frankfurt.de [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany)

    2015-08-15

    (Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC{sub 50} values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G{sub 2}/M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like

  15. Making a difference? A comparison between multi-sensory and regular storytelling for persons with profound intellectual and multiple disabilities.

    Science.gov (United States)

    Ten Brug, A; Van der Putten, A A J; Penne, A; Maes, B; Vlaskamp, C

    2016-11-01

    Multi-sensory storytelling (MSST) was developed to include persons with profound intellectual and multiple disabilities in storytelling culture. In order to increase the listeners' attention, MSST stories are individualised and use multiple sensory stimuli to support the verbal text. In order to determine the value of MSST, this study compared listeners' attention under two conditions: (1) being read MSST books and (2) being read regular stories. A non-randomised control study was executed in which the intervention group read MSST books (n = 45) and a comparison group (n = 31) read regular books. Books were read 10 times during a 5-week period. The 1st, 5th and 10th storytelling sessions were recorded on video in both groups, and the percentage of attention directed to the book and/or stimuli and to the storyteller was scored by a trained and independent rater. Two repeated measure analyses (with the storytelling condition as a between-subject factor and the three measurements as factor) were performed to determine the difference between the groups in terms of attention directed to the book/stimuli (first analysis) and storyteller (second analysis). A further analysis established whether the level of attention changed between the reading sessions and whether there was an interaction effect between the repetition of the book and the storytelling condition. The attention directed to the book and/or the stimuli was significantly higher in the MSST group than in the comparison group. No significant difference between the two groups was found in the attention directed to the storyteller. For MSST stories, most attention was observed during the fifth reading session, while for regular stories, the fifth session gained least attentiveness from the listener. The persons with profound intellectual and multiple disabilities paid more attention to the book and/or stimuli in the MSST condition compared with the regular story telling group. Being more attentive towards

  16. Communication strategies and intensive interaction therapy meet the theology of the body: bioethics in dialogue with people with profound disabilities.

    Science.gov (United States)

    Matthews, Pia

    2013-01-01

    Academic bioethics does not appear to be interested in communication and its ethical concerns unless communication is to do with issues such as capacity, consent, truth telling and confidentiality. In contrast practitioners are interested in actually communicating with their patients and they are often particularly perplexed when it comes to people with profound disabilities where communication appears disrupted. Although some new and not so new communication strategies, and especially intensive interaction, are available, little has been written on either the ethical concerns these may present or the deeper concepts that underpin them. This article explores the practical applications of some of these communication strategies. By engaging these strategies with theology, and specifically Pope John Paul's Theology of the Body, this article identifies and addresses some significant ethical issues that may arise, notably the risk of dualism and of objectifying the human person. Moreover it provides communication strategies with a rationale that goes beyond practicalities to one based on respect for human dignity, justice and solidarity.

  17. Systematic Moiety Variations of Ultrashort Peptides Produce Profound Effects on Self-Assembly, Nanostructure Formation, Hydrogelation, and Phase Transition

    KAUST Repository

    Chan, Kiat Hwa

    2017-10-04

    Self-assembly of small biomolecules is a prevalent phenomenon that is increasingly being recognised to hold the key to building complex structures from simple monomeric units. Small peptides, in particular ultrashort peptides containing up to seven amino acids, for which our laboratory has found many biomedical applications, exhibit immense potential in this regard. For next-generation applications, more intricate control is required over the self-assembly processes. We seek to find out how subtle moiety variation of peptides can affect self-assembly and nanostructure formation. To this end, we have selected a library of 54 tripeptides, derived from systematic moiety variations from seven tripeptides. Our study reveals that subtle structural changes in the tripeptides can exert profound effects on self-assembly, nanostructure formation, hydrogelation, and even phase transition of peptide nanostructures. By comparing the X-ray crystal structures of two tripeptides, acetylated leucine-leucine-glutamic acid (Ac-LLE) and acetylated tyrosine-leucine-aspartic acid (Ac-YLD), we obtained valuable insights into the structural factors that can influence the formation of supramolecular peptide structures. We believe that our results have major implications on the understanding of the factors that affect peptide self-assembly. In addition, our findings can potentially assist current computational efforts to predict and design self-assembling peptide systems for diverse biomedical applications.

  18. A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay.

    Science.gov (United States)

    Schoch, Kelly; Meng, Linyan; Szelinger, Szabolcs; Bearden, David R; Stray-Pedersen, Asbjorg; Busk, Oyvind L; Stong, Nicholas; Liston, Eriskay; Cohn, Ronald D; Scaglia, Fernando; Rosenfeld, Jill A; Tarpinian, Jennifer; Skraban, Cara M; Deardorff, Matthew A; Friedman, Jeremy N; Akdemir, Zeynep Coban; Walley, Nicole; Mikati, Mohamad A; Kranz, Peter G; Jasien, Joan; McConkie-Rosell, Allyn; McDonald, Marie; Wechsler, Stephanie Burns; Freemark, Michael; Kansagra, Sujay; Freedman, Sharon; Bali, Deeksha; Millan, Francisca; Bale, Sherri; Nelson, Stanley F; Lee, Hane; Dorrani, Naghmeh; Goldstein, David B; Xiao, Rui; Yang, Yaping; Posey, Jennifer E; Martinez-Agosto, Julian A; Lupski, James R; Wangler, Michael F; Shashi, Vandana

    2017-02-02

    Whole-exome sequencing (WES) has increasingly enabled new pathogenic gene variant identification for undiagnosed neurodevelopmental disorders and provided insights into both gene function and disease biology. Here, we describe seven children with a neurodevelopmental disorder characterized by microcephaly, profound developmental delays and/or intellectual disability, cataracts, severe epilepsy including infantile spasms, irritability, failure to thrive, and stereotypic hand movements. Brain imaging in these individuals reveals delay in myelination and cerebral atrophy. We observe an identical recurrent de novo heterozygous c.892C>T (p.Arg298Trp) variant in the nucleus accumbens associated 1 (NACC1) gene in seven affected individuals. One of the seven individuals is mosaic for this variant. NACC1 encodes a transcriptional repressor implicated in gene expression and has not previously been associated with germline disorders. The probability of finding the same missense NACC1 variant by chance in 7 out of 17,228 individuals who underwent WES for diagnoses of neurodevelopmental phenotypes is extremely small and achieves genome-wide significance (p = 1.25 × 10 -14 ). Selective constraint against missense variants in NACC1 makes this excess of an identical missense variant in all seven individuals more remarkable. Our findings are consistent with a germline recurrent mutational hotspot associated with an allele-specific neurodevelopmental phenotype in NACC1. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  19. Macroevolutionary consequences of profound climate change on niche evolution in marine molluscs over the past three million years

    Science.gov (United States)

    Saupe, E.E.; Hendricks, J.R.; Portell, R.W.; Dowsett, Harry J.; Haywood, A. M.; Hunter, S.J.; Lieberman, B.S.

    2014-01-01

    In order to predict the fate of biodiversity in a rapidly changing world, we must first understand how species adapt to new environmental conditions. The long-term evolutionary dynamics of species' physiological tolerances to differing climatic regimes remain obscure. Here, we unite palaeontological and neontological data to analyse whether species' environmental tolerances remain stable across 3 Myr of profound climatic changes using 10 phylogenetically, ecologically and developmentally diverse mollusc species from the Atlantic and Gulf Coastal Plains, USA. We additionally investigate whether these species' upper and lower thermal tolerances are constrained across this interval. We find that these species' environmental preferences are stable across the duration of their lifetimes, even when faced with significant environmental perturbations. The results suggest that species will respond to current and future warming either by altering distributions to track suitable habitat or, if the pace of change is too rapid, by going extinct. Our findings also support methods that project species' present-day environmental requirements to future climatic landscapes to assess conservation risks.

  20. Comparison of swallowing outcomes of laryngotracheal separation versus total laryngectomy in a validated ovine model of profound oropharyngeal dysphagia.

    Science.gov (United States)

    Venkatesan, N N; Johnson, C M; Siddiqui, M T; Cates, D J; Kuhn, M A; Postma, G N; Belafsky, P C

    2017-04-01

    To validate the ovine model of profound oropharyngeal dysphagia and compare swallowing outcomes of laryngotracheal separation with those of total laryngectomy. Under real-time fluoroscopy, swallowing trials were conducted using the head and neck of two Dorper cross ewes and one human cadaver, secured in lateral fluoroscopic orientation. Barium trials were administered at baseline, pre- and post-laryngohyoid suspension, following laryngotracheal separation, and following laryngectomy in the ovine model. Mean pre-intervention Penetration Aspiration Scale and National Institutes of Health Swallow Safety Scale scores were 8 ± 0 and 6 ± 0 respectively in sheep and human cadavers, with 100 per cent intra- and inter-species reproducibility. These scores improved to 1 ± 0 and 2 ± 0 post-laryngohyoid suspension (p < 0.01). Aerodigestive tract residue was 18.6 ± 2.4 ml at baseline, 15.4 ± 3.8 ml after laryngotracheal separation and 3.0 ± 0.7 ml after total laryngectomy (p < 0.001). The ovine model displayed perfect intra- and inter- species reliability for the Penetration Aspiration Scale and Swallow Safety Scale. Less aerodigestive tract residue after narrow-field laryngectomy suggests that swallowing outcomes after total laryngectomy are superior to those after laryngotracheal separation.

  1. Butyrate induces profound changes in gene expression related to multiple signal pathways in bovine kidney epithelial cells

    Directory of Open Access Journals (Sweden)

    Li CongJun

    2006-09-01

    Full Text Available Abstract Background Global gene expression profiles of bovine kidney epithelial cells regulated by sodium butyrate were investigated with high-density oligonucleotide microarrays. The bovine microarray with 86,191 distinct 60mer oligonucleotides, each with 4 replicates, was designed and produced with Maskless Array Synthesizer technology. These oligonucleotides represent approximately 45,383 unique cattle sequences. Results 450 genes significantly regulated by butyrate with a median False Discovery Rate (FDR = 0 % were identified. The majority of these genes were repressed by butyrate and associated with cell cycle control. The expression levels of 30 selected genes identified by the microarray were confirmed using real-time PCR. The results from real-time PCR positively correlated (R = 0.867 with the results from the microarray. Conclusion This study presented the genes related to multiple signal pathways such as cell cycle control and apoptosis. The profound changes in gene expression elucidate the molecular basis for the pleiotropic effects of butyrate on biological processes. These findings enable better recognition of the full range of beneficial roles butyrate may play during cattle energy metabolism, cell growth and proliferation, and possibly in fighting gastrointestinal pathogens.

  2. Family influences on the cognitive development of profoundly deaf children: exploring the effects of socioeconomic status and siblings.

    Science.gov (United States)

    Macaulay, Catrin E; Ford, Ruth M

    2013-10-01

    We evaluated the cognitive development of 48 profoundly deaf children from hearing families (born 1994-2002, mean age M = 8.0 years at time of test, none of whom had received early auditory-verbal therapy) as a function of family socioeconomic status and number of siblings. Overall, the deaf children matched a younger group of 47 hearing controls (M = 4.6 years) on verbal ability, theory of mind, and cognitive inhibition. Partial correlations (controlling for age) revealed positive relations in the hearing group between maternal education and inhibition, between number of younger siblings and references to emotions, and between number of close-in-age siblings and references to desires and false beliefs. In the deaf group, there were positive relations between household income and memory span, between maternal education and references to false beliefs, and between number of younger siblings and nonverbal ability. In contrast, deaf children with a greater number of older siblings aged ≤12 years showed inferior memory span, inhibition, belief understanding, picture-sequencing accuracy, and mental-state language, suggesting that they failed to compete successfully with older siblings for their parents' attention and material resources. We consider the implications of the findings for understanding birth-order effects on deaf and language-impaired children.

  3. JAK inhibition induces silencing of T Helper cytokine secretion and a profound reduction in T regulatory cells.

    Science.gov (United States)

    Keohane, Clodagh; Kordasti, Shahram; Seidl, Thomas; Perez Abellan, Pilar; Thomas, Nicholas S B; Harrison, Claire N; McLornan, Donal P; Mufti, Ghulam J

    2015-10-01

    CD4(+) T cells maintain cancer surveillance and immune tolerance. Chronic inflammation has been proposed as a driver of clonal evolution in myeloproliferative neoplasms (MPN), suggesting that T cells play an important role in their pathogenesis. Treatment with JAK inhibitors (JAKi) results in improvements in MPN-associated constitutional symptoms as well as reductions in splenomegaly. However, effects of JAKi on T cells in MPN are not well established and the baseline immune signature remains unclear. We investigated the frequency and function of CD4(+) T cell subsets in 50 MPN patients at baseline as well as during treatment with either ruxolitinib or fedratinib in a subset. We show that CD4(+)  CD127(low)  CD25(high)  FOXP3(+) T regulatory cells are reduced in MPN patients compared to healthy controls and that this decrease is even more pronounced following JAKi therapy. Moreover, we show that after 6 months of treatment the number of T helper (Th)-17 cells increased. We also describe a functional 'silencing' of T helper cells both in vivo and in vitro and a blockade of pro-inflammatory cytokines from these cells. This profound effect of JAKi on T cell function may underlay augmented rates of atypical infections that have been reported with use of these drugs. © 2015 John Wiley & Sons Ltd.

  4. Developing and Implementing School for Highly Gifted, Exceptionally Gifted, and Profoundly Gifted Students: An Interview with Lynette Breedlove

    Directory of Open Access Journals (Sweden)

    Engin KARADUMAN

    2013-12-01

    Full Text Available According to research, while moderately gifted students can often fit in the regular classrooms with differentiated instructions, pull-out programs, or acceleration options, highly gifted students do better when they are grouped with other intellectually-advanced peers in accordance with their strengths, interests, and background knowledge of a topic. Each of these students requires special attention and management strategies to develop better cognitive, social, emotional, and physical skills. Thanks to the grouping strategy, highly gifted students can study concepts at the appropriate pace, depth, and complexity so that these students feel valued and normal (Neville, 2007; Rogers, 2007. In order to fully meet these students’ needs, creating a school for highly, exceptionally, and profoundly gifted students would be a more beneficial plan compared to requiring them to stay within the regular classroom, accelerating, or grade skipping. Rogers (2002 pointed out that these students showed more academic growth by studying with other intellectual peers in separate classrooms. According to VanTassel-Baska (2006, identification, curriculum, program design, staff development, parental involvement assessment, and evaluation areas were essential for gifted program development. In accordance with the program development guidelines noted above, in this presentation, the process of developing and implementing a program for highly gifted students in Science, Math, Reading, and Social Studies will be provided based on an interview with Lynette Breedlove, Ph.D. who is the director of Advanced Academic Studies & Secondary Counseling at Spring Branch Independent School District in Houston, TX.

  5. Are Auditory Steady-State Responses Useful to Evaluate Severe-to-Profound Hearing Loss in Children?

    Science.gov (United States)

    Grasel, Signe Schuster; de Almeida, Edigar Rezende; Beck, Roberto Miquelino de Oliveira; Goffi-Gomez, Maria Valéria Schmidt; Ramos, Henrique Faria; Rossi, Amanda Costa; Koji Tsuji, Robinson; Bento, Ricardo Ferreira; de Brito, Rubens

    2015-01-01

    To evaluate Auditory Steady-State Responses (ASSR) at high intensities in pediatric cochlear implant candidates and to compare the results to behavioral tests responses. This prospective study evaluated 42 children with suspected severe-to-profound hearing loss, aged from 3 to 72 months. All had absent ABR and OAE responses. ASSR were evoked using binaural single frequency stimuli at 110 dB HL with a 10 dB down-seeking procedure. ASSR and behavioral test results were compared. Forty-two subjects completed both ASSR and behavioral evaluation. Eleven children (26.2%) had bilateral responses. Four (9.5%) showed unilateral responses in at least two frequencies, all confirmed by behavioral results. Overall 61 ASSR responses were obtained, most (37.7%) in 500 Hz. Mean thresholds were between 101.3 and 104.2 dB HL. Among 27 subjects with absent ASSR, fifteen had no behavioral responses. Seven subjects showed behavioral responses with absent ASSR responses. No spurious ASSR responses were observed at 100 or 110 dB HL. ASSR is a valuable tool to detect residual hearing. No false-positive ASSR results were observed among 42 children, but in seven cases with absent ASSR, the test underestimated residual hearing as compared to the behavioral responses.

  6. Are Auditory Steady-State Responses Useful to Evaluate Severe-to-Profound Hearing Loss in Children?

    Directory of Open Access Journals (Sweden)

    Signe Schuster Grasel

    2015-01-01

    Full Text Available Objective. To evaluate Auditory Steady-State Responses (ASSR at high intensities in pediatric cochlear implant candidates and to compare the results to behavioral tests responses. Methods. This prospective study evaluated 42 children with suspected severe-to-profound hearing loss, aged from 3 to 72 months. All had absent ABR and OAE responses. ASSR were evoked using binaural single frequency stimuli at 110 dB HL with a 10 dB down-seeking procedure. ASSR and behavioral test results were compared. Results. Forty-two subjects completed both ASSR and behavioral evaluation. Eleven children (26.2% had bilateral responses. Four (9.5% showed unilateral responses in at least two frequencies, all confirmed by behavioral results. Overall 61 ASSR responses were obtained, most (37.7% in 500 Hz. Mean thresholds were between 101.3 and 104.2 dB HL. Among 27 subjects with absent ASSR, fifteen had no behavioral responses. Seven subjects showed behavioral responses with absent ASSR responses. No spurious ASSR responses were observed at 100 or 110 dB HL. Conclusion. ASSR is a valuable tool to detect residual hearing. No false-positive ASSR results were observed among 42 children, but in seven cases with absent ASSR, the test underestimated residual hearing as compared to the behavioral responses.

  7. Communication training for centre-based carers of children with severe or profound disabilities in the Western Cape, South Africa

    Directory of Open Access Journals (Sweden)

    Martha Geiger

    2012-09-01

    Full Text Available The purpose of this paper is to provide a preliminary, qualitative review of an approach to training centre-based carers in supporting basic communication development and providing communication opportunities for the children with severe and profound disabilities in their care. In South Africa, these children are often the most neglected in terms of planning and providing appropriate interventions. For those with severe communication disabilities, an additional lack is in the area of the basic human right to meaningful interactions and communication. Sustainable strategies to provide opportunities for basic communication development of these children are urgently sought. Several effective international and local parent training programmes have been developed, but the urgent need remains to train centre-based carers who are taking care of groups of diversely disabled children in severely under-resourced settings. Non-profit organisations (NPOs have been exploring practical centre-based approaches to skills sharing in physical rehabilitation, activities for daily living, feeding and support for basic communication development. As a freelance speech therapist contracted by four NPOs to implement hands-on training in basic communication for centre-based carers of non-verbal children, the author describes a training approach that evolved over three years, in collaboration with the carers and centre managements. Implications for training (for speech therapists and for community-based rehabilitation workers and for further research are identified.

  8. Cinnamic Acid Is Partially Involved in Propolis Immunomodulatory Action on Human Monocytes

    Directory of Open Access Journals (Sweden)

    Bruno José Conti

    2013-01-01

    Full Text Available Propolis is a beehive product used in traditional medicine due to its biological properties. It shows a complex chemical composition including phenolics, such as cinnamic acid (Ci. The mechanisms of action of propolis have been the subject of research recently; however, the involvement of Ci on propolis activity was not investigated on immune cells. Ci effects were evaluated on human monocytes, assessing the expression of Toll-like receptors (TLRs, HLA-DR, and CD80. Cytokine production (TNF-α and IL-10 and the fungicidal activity of monocytes were evaluated as well. Data showed that Ci downregulated TLR-2, HLA-DR, and CD80 and upregulated TLR-4 expression by human monocytes. High concentrations of Ci inhibited both TNF-α and IL-10 production, whereas the same concentrations induced a higher fungicidal activity against Candida albicans. TNF-α and IL-10 production was decreased by blocking TLR-4, while the fungicidal activity of monocytes was not affected by blocking TLRs. These results suggest that Ci modulated antigen receptors, cytokine production, and the fungicidal activity of human monocytes depending on concentration, and TLR-4 may be involved in its mechanism of action. Ci seemed to be partially involved in propolis activities.

  9. Magnetic properties of variably serpentinized peridotites and their implication for the evolution of oceanic core complexes

    NARCIS (Netherlands)

    Maffione, M.; Morris, A.; Plümper, O.|info:eu-repo/dai/nl/37155960X; van Hinsbergen, D.J.J.|info:eu-repo/dai/nl/269263624

    Serpentinization of ultramafic rocks during hydrothermal alteration at mid-ocean ridges profoundly changes the physical, chemical, rheological, and magnetic properties of the oceanic lithosphere. There is renewed interest in this process following the discovery of widespread exposures of

  10. The immunomodulatory effects of Zn-incorporated micro/nanostructured coating in inducing osteogenesis.

    Science.gov (United States)

    Zhang, Ranran; Liu, Xujie; Xiong, Zhiyuan; Huang, Qianli; Yang, Xing; Yan, Hao; Ma, Jing; Feng, Qingling; Shen, Zhijian

    2018-03-08

    Micro/nanostructured TiO 2 /ZnO coating has been shown to possess multiple functions, including antibacterial activity and bioactivity. Osteoblast-like SaOS-2 cells were employed for evaluating the in vitro osteogenic capacity of this coating and positive results were obtained. However, traditional principles of osseointegration focus only on the osteogenic differentiation alone. The effects of immunomodulation on the osteogenic activity have been largely ignored. In this study, the inflammatory responses of macrophages on the micro/nanostructured TiO 2 /ZnO coating were investigated. The extract media of macrophage cell line RAW264.7 cultured on the TiO 2 /ZnO coating were collected as indirect co-culture conditioned media. The osteogenic activity of SaOS-2 cells in the conditioned media was investigated. Adhesion, ALP activity and extracellular mineralization of cells grown in the conditioned media extracted from the micro/nanostructured TiO 2 /ZnO coating were found to be enhanced, compared to those grown in the conditioned media extracted from the macroporous TiO 2 coating. The immune microenvironment produced by the micro/nanostructured TiO 2 /ZnO coating showed excellent capacity to promote osteogenesis, indicating that this coating could be a promising candidate for implant surface modification in orthopaedic and dental applications. Furthermore, this work could help us understand the interplay between the host immune system and the osteoimmunomodulatory properties of the biomaterials, and optimize the design for coating biomaterials.

  11. Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis

    Science.gov (United States)

    Stanton, M. Mark; Nelson, Lisa K.; Benediktsson, Hallgrimur; Hollenberg, Morley D.; Buret, Andre G.; Ceri, Howard

    2013-01-01

    Background. Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis. Methods. Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation. Results. Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice. Conclusions. PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor. PMID:24459330

  12. Tamm–Horsfall Protein is a Potent Immunomodulatory Molecule and a Disease Biomarker in the Urinary System

    Directory of Open Access Journals (Sweden)

    Tsai-Hung Wu

    2018-01-01

    Full Text Available Tamm–Horsfall protein (THP, or uromodulin (UMOD, is an 80–90-kDa phosphatidylinositol-anchored glycoprotein produced exclusively by the renal tubular cells in the thick ascending limb of the loop of Henle. Physiologically, THP is implicated in renal countercurrent gradient formation, sodium homeostasis, blood pressure regulation, and a defense molecule against infections in the urinary system. Investigations have also revealed that THP is an effective binding ligand for serum albumin, immunoglobulin G light chains, complement components C1 and C1q, interleukin (IL-1β, IL-6, IL-8, tumor necrosis factor (TNF-α, and interferon-γ through its carbohydrate side chains for maintaining circulatory and renal immune homeostasis. Thus, THP can be regarded as part of the innate immune system. UMOD mutations play crucial roles in congenital urolithiasis, hereditary hyperuricemia/gout, and medullary cystic kidney diseases. Recent investigations have focused on the immunomodulatory effects of THP on immune cells and on THP as a disease biomarker of acute and chronic kidney diseases. Our studies have suggested that normal urinary THP, through its epidermal growth factor (EGF-like domains, binds to the surface-expressed EGF-like receptors, cathepsin G, or lactoferrin to enhance polymorphonuclear leukocyte phagocytosis, proinflammatory cytokine production by monocytes/macrophages, and lymphocyte proliferation by activating the Rho family and mitogen-activated protein kinase signaling pathways. Furthermore, our data support both an intact protein core structure and carbohydrate side chains are important for the different protein-binding capacities of THP. Prospectively, parts of the whole THP molecule may be used for anti-TNF-α therapy in inflammatory diseases, autoantibody-depleting therapy in autoimmune disorders, and immune intensification in immunocompromised hosts.

  13. Comparative study on immuno-modulatory effect of anticoccidial vaccines and a coccidiostat on nd vaccinated broiler chicks

    International Nuclear Information System (INIS)

    Hazeen, M.K.; Mustafa, M.Y.; But, T.M.

    2007-01-01

    105 day old broiler chicks were divided into 5 equal groups with 21 chicks in each i.e. A (non vaccinated, non medicated control), B (ND vaccinated control), C (administered with ND vaccine Lasota and Eimeria vaccine EV), D (NDV and immucox) and E (administered with NDV vaccine and coccidiostat). The comparative immunomodulatory effects of EV, immucox and Sacox were worked out on the basis of the GMT levels in Newcastle disease vaccinated birds along with the non-vaccinated and non-medicated control birds. These titres were evaluated by using HA and H1 tests on the sera of these experimental chicks. Other parameters i.e. morbidity, mortality, OPG, weight gain, FCR, Postmortem findings, Bursal/body weight ratio, weight, size and texture of spleen, thymus and liver were also assessed. The birds that were kept as NDV vaccinated control (group B) had the highest body weight and showed best FCR. The birds of unmedicated, unvaccinated control group (A) secured 2nd position regarding weight gain and FCR. Among the three experimental groups (C, D and E), the birds from group C (NDV + EV) had higher body weight than group D and E. Feed conversion ratio (FCR) of the birds of group C was also found to be better than the birds belonging to group D and E. The number of oocysts per gm of faeces showed gradual decrease and became nil on the observation of day 33 of the experiment, as the birds became solidly immune against Eimeria infection at this age. The birds belonging to group B (NDV vaccinated control) had shown the highest antibody titers while the birds of group A (unvaccinated unmedicated control) had the lowest antibody titres. Among the three experimental groups (C, D and E) the birds from group C had the higher antibody titres as compared to other two groups (D and E) on day 49. (author)

  14. Lipopolysaccharide can modify differentiation and immunomodulatory potential of periodontal ligament stem cells via ERK1,2 signaling.

    Science.gov (United States)

    Kukolj, Tamara; Trivanović, Drenka; Djordjević, Ivana Okić; Mojsilović, Slavko; Krstić, Jelena; Obradović, Hristina; Janković, Srdja; Santibanez, Juan Francisco; Jauković, Aleksandra; Bugarski, Diana

    2018-01-01

    Lipopolysaccharide (LPS) is a pertinent deleterious factor in oral microenvironment for cells which are carriers of regenerative processes. The aim of this study was to investigate the emerging in vitro effects of LPS (Escherichia coli) on human periodontal ligament stem cell (PDLSC) functions and associated signaling pathways. We demonstrated that LPS did not affect immunophenotype, proliferation, viability, and cell cycle of PDLSCs. However, LPS modified lineage commitment of PDLSCs inhibiting osteogenesis by downregulating Runx2, ALP, and Ocn mRNA expression, while stimulating chondrogenesis and adipogenesis by upregulating Sox9 and PPARγ mRNA expression. LPS promoted myofibroblast-like phenotype of PDLSCs, since it significantly enhanced PDLSC contractility, as well as protein and/or gene expression of TGF-β, fibronectin (FN), α-SMA, and NG2. LPS also increased protein and gene expression levels of anti-inflammatory COX-2 and pro-inflammatory IL-6 molecules in PDLSCs. Inhibition of peripheral blood mononuclear cells (MNCs) transendothelial migration in presence of LPS-treated PDLSCs was accompanied by the reduction of CD29 expression within MNCs. However, LPS treatment did not change the inhibitory effect of PDLSCs on mitogen-stimulated proliferation of CD4 + and the ratio of CD4 + CD25 high /CD4 + CD25 low lymphocytes. LPS-treated PDLSCs did not change the frequency of CD34 + and CD45 + cells, but decreased the frequency of CD33 + and CD14 + myeloid cells within MNCs. Moreover, LPS treatment attenuated the stimulatory effect of PDLSCs on CFC activity of MNCs, predominantly the CFU-GM number. The results indicated that LPS-activated ERK1,2 was at least partly involved in the observed effects on PDLSC differentiation capacity, acquisition of myofibroblastic attributes, and changes of their immunomodulatory features. © 2017 Wiley Periodicals, Inc.

  15. A Systematic Review of Innate Immunomodulatory Effects of Household Air Pollution Secondary to the Burning of Biomass Fuels.

    Science.gov (United States)

    Lee, Alison; Kinney, Patrick; Chillrud, Steve; Jack, Darby

    2015-01-01

    Household air pollution (HAP)-associated acute lower respiratory infections cause 455,000 deaths and a loss of 39.1 million disability-adjusted life years annually. The immunomodulatory mechanisms of HAP are poorly understood. The aim of this study was to conduct a systematic review of all studies examining the mechanisms underlying the relationship between HAP secondary to solid fuel exposure and acute lower respiratory tract infection to evaluate current available evidence, identify gaps in knowledge, and propose future research priorities. We conducted and report on studies in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In all, 133 articles were fully reviewed and main characteristics were detailed, namely study design and outcome, including in vivo versus in vitro and pollutants analyzed. Thirty-six studies were included in a nonexhaustive review of the innate immune system effects of ambient air pollution, traffic-related air pollution, or wood smoke exposure of developed country origin. Seventeen studies investigated the effects of HAP-associated solid fuel (biomass or coal smoke) exposure on airway inflammation and innate immune system function. Particulate matter may modulate the innate immune system and increase susceptibility to infection through a) alveolar macrophage-driven inflammation, recruitment of neutrophils, and disruption of barrier defenses; b) alterations in alveolar macrophage phagocytosis and intracellular killing; and c) increased susceptibility to infection via upregulation of receptors involved in pathogen invasion. HAP secondary to the burning of biomass fuels alters innate immunity, predisposing children to acute lower respiratory tract infections. Data from biomass exposure in developing countries are scarce. Further study is needed to define the inflammatory response, alterations in phagocytic function, and upregulation of receptors important in bacterial and viral

  16. Characterization and immunomodulatory activity of an exopolysaccharide produced by Lactobacillus plantarum JLK0142 isolated from fermented dairy tofu.

    Science.gov (United States)

    Wang, Ji; Wu, Tong; Fang, Xiaobin; Min, Weihong; Yang, Zhennai

    2018-04-21

    A purified neutral exopolysaccharide (EPS) designated as EPS0142 was obtained from Lactobacillus plantarum JLK0142. EPS0142 consisted of glucose and galactose in an approximate molar ratio of 2.13:1.06 and had a molecular weight of 1.34 × 10 5  Da. The FT-IR spectrum showed that EPS0142 had a typical polysaccharide absorption pattern. 1 H NMR and 13 C NMR spectra analysis showed the presence of N-acetylated sugar residues. EPS0142 had no toxic effects on RAW 264.7 cells and significantly improved their phagocytic activity and NO secretion in vitro. Further in vivo studies revealed that the spleen index and splenic lymphocyte proliferation activities of the cyclophosphamide-induced immunosuppression mice treated with a middle-dose (50 mg/kg body weight) or a high-dose (100 mg/kg body weight) of EPS0142 were significantly increased (P < 0.01). In addition, the intestinal immunoglobulin A (sIgA) content and the serum levels of the cytokines, IL-2 and TNF-α, were also significantly (P < 0.05) improved in the high-dose EPS0142 group compared to that in the model control group. These data indicate that the EPS isolated from L. plantarum JLK0142 can effectively improve the immunomodulatory activity of RAW 264.7 cells and stimulate the immune system in cyclophosphamide-induced immunosuppressed mice. Copyright © 2018. Published by Elsevier B.V.

  17. Different immunomodulatory effects associated with sub-micrometer particles in ambient air from rural, urban and industrial areas

    International Nuclear Information System (INIS)

    Wichmann, Gunnar; Franck, Ulrich; Herbarth, Olf; Rehwagen, Martina; Dietz, Andreas; Massolo, Laura; Ronco, Alicia; Mueller, Andrea

    2009-01-01

    Immunomodulatory effects of chemicals adsorbed to particles with aerodynamic diameter below 0.49 μm (PM 0.5 ) collected in winter 2001 at three sampling points (industrial area [LPIn], traffic-influenced urban area [LPCi], and control area [LPCo]) of La Plata, Argentina, were investigated. The sampling of particulate matter was carried out with high-volume collectors using cascade impactors. PM 0.5 -adsorbed compounds were hexane-extracted by accelerated solvent extraction. For immunological investigations, human peripheral blood lymphocytes were activated by phytohemagglutinin and exposed to dimethyl-sulfoxide dilutions of PM 0.5 -extracts for 24 h. Vitality/proliferation was quantified using MTT, released interferon-γ (IFN-γ) and interleukin-4 (IL-4) by ELISA. Cytokine production but not vitality/proliferation was significantly suppressed by all of the highest extract concentrations. Generally, suppression of IFN-γ by PM 0.5 -extracts was stronger than those of IL-4. Based on administered mass of PM 0.5 , all extracts suppressed IFN-γ production nearly uniform. Contrary, LPCi-extracts exerted maximum IFN-γ suppression based either on air volume or regarding PM 0.5 -adsorbed PAH. Also the ranking of PM 0.5 -associated effects on IL-4 production differs in dependence of the chosen reference points, either mass or [μg/ml] or air volume [m 3 /ml] related dust quantities in cell culture. Based on the corresponding air volume, LPCi-extracts inhibited IL-4 production to the maximum extend, whereas suppression of IL-4 was comparable based on concentrations. This indicates that not only the disparate PM 0.5 -masses in air cause varying impacts, but also that disparities in PM 0.5 -adsorbed chemicals provoke different effects on immune responses and shifts in the regulatory balance that might have implications for allergy and cancer development

  18. Speech and language therapists' approaches to communication intervention with children and adults with profound and multiple learning disability.

    Science.gov (United States)

    Goldbart, Juliet; Chadwick, Darren; Buell, Susan

    2014-11-01

    People with profound intellectual and multiple disabilities (PMLD) have communication impairments as one defining characteristic. To explore speech and language therapists' (SLTs) decision making in communication interventions for people with PMLD, in terms of the intervention approaches used, the factors informing the decisions to use specific interventions and the extent to which the rationales underpinning these decisions related to the components of evidence based practice (EBP), namely empirical evidence, clinical experience and client/carer views and values. A questionnaire on communication assessment and intervention for people with PMLD was sent to SLTs in the UK to elicit information on: the communication intervention approaches they used; their rationales for their intervention choices; their use of published evidence to inform decision making. Intensive interaction and objects of reference were the communication interventions most often used with people with PMLD, with some differences between children and adults evident. Rationales provided conformed somewhat to the EBP framework though extension of the existing framework and addition of practical and organizational considerations led to a revised typology of rationale for decision making. Rationales most frequently related to the empowerment, development and behavioural preferences of the person with PMLD. Empirical research evidence was seldom mentioned by SLTs as informing intervention decision making leading to very diverse practice. There is a need for further research on the effectiveness of commonly used but under-evaluated interventions. There is also a need to alert SLTs to the evidence base supporting other approaches, particularly switch-based, cause and effect approaches. © 2014 Royal College of Speech and Language Therapists.

  19. Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects.

    Science.gov (United States)

    Kechagias, S; Ernersson, A; Dahlqvist, O; Lundberg, P; Lindström, T; Nystrom, F H

    2008-05-01

    To study the effect of fast-food-based hyper-alimentation on liver enzymes and hepatic triglyceride content (HTGC). Prospective interventional study with parallel control group. University Hospital of Linköping, Sweden. 12 healthy men and six healthy women with a mean (SD) age of 26 (6.6) years and a matched control group. Subjects in the intervention group aimed for a body weight increase of 5-15% by eating at least two fast-food-based meals a day with the goal to double the regular caloric intake in combination with adoption of a sedentary lifestyle for 4 weeks. Weekly changes of serum aminotransferases and HTGC measured by proton nuclear magnetic resonance spectroscopy at baseline and after the intervention. Subjects in the intervention group increased from 67.6 (9.1) kg to 74.0 (11) kg in weight (p19 U/l, men >30 U/l) during the intervention. Sugar (mono- and disaccharides) intake during week 3 correlated with the maximal ALT/baseline ALT ratio (r = 0.62, p = 0.006). HTGC increased from 1.1 (1.9)% to 2.8 (4.8)%, although this was not related to the increase in ALT levels. ALT levels were unchanged in controls. Hyper-alimentation per se can induce profound ALT elevations in less than 4 weeks. Our study clearly shows that in the evaluation of subjects with elevated ALT the medical history should include not only questions about alcohol intake but also explore whether recent excessive food intake has occurred.

  20. Understanding minds: early cochlear implantation and the development of theory of mind in children with profound hearing impairment.

    Science.gov (United States)

    Sundqvist, Annette; Lyxell, Björn; Jönsson, Radoslava; Heimann, Mikael

    2014-03-01

    The present study investigates how auditory stimulation from cochlear implants (CI) is associated with the development of Theory of Mind (ToM) in severely and profoundly hearing impaired children with hearing parents. Previous research has shown that deaf children of hearing parents have a delayed ToM development. This is, however, not always the case with deaf children of deaf parents, who presumably are immersed in a more vivid signing environment. Sixteen children with CI (4.25 to 9.5 years of age) were tested on measures of cognitive and emotional ToM, language and cognition. Eight of the children received their first implant relatively early (before 27 months) and half of them late (after 27 months). The two groups did not differ in age, gender, language or cognition at entry of the study. ToM tests included the unexpected location task and a newly developed Swedish social-emotional ToM test. The tests aimed to test both cognitive and emotional ToM. A comparison group of typically developing hearing age matched children was also added (n=18). Compared to the comparison group, the early CI-group did not differ in emotional ToM. The late CI-group differed significantly from the comparison group on both the cognitive and emotional ToM tests. The results revealed that children with early cochlear implants solved ToM problems to a significantly higher degree than children with late implants, although the groups did not differ on language or cognitive measures at baseline. The outcome suggests that early cochlear implantation for deaf children in hearing families, in conjunction with early social and communicative stimulation in a language that is native to the parents, can provide a foundation for a more normalized ToM development. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.