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  1. Article ; Online: Immunosuppression by hydroxychloroquine: mechanistic proof in in vitro experiments but limited systemic activity in a randomized placebo-controlled clinical pharmacology study.

    In 't Veld, Aliede E / Grievink, Hendrika W / van der Plas, Johan L / Eveleens Maarse, Boukje C / van Kraaij, Sebastiaan J W / Woutman, Tess D / Schoonakker, Mascha / Klarenbeek, Naomi B / de Kam, Marieke L / Kamerling, Ingrid M C / Jansen, Manon A A / Moerland, Matthijs

    Immunologic research

    2023  Volume 71, Issue 4, Page(s) 617–627

    Abstract: Based on its wide range of immunosuppressive properties, hydroxychloroquine (HCQ) is used for the treatment of several autoimmune diseases. Limited literature is available on the relationship between HCQ concentration and its immunosuppressive effect. To ...

    Abstract Based on its wide range of immunosuppressive properties, hydroxychloroquine (HCQ) is used for the treatment of several autoimmune diseases. Limited literature is available on the relationship between HCQ concentration and its immunosuppressive effect. To gain insight in this relationship, we performed in vitro experiments in human PBMCs and explored the effect of HCQ on T and B cell proliferation and Toll-like receptor (TLR)3/TLR7/TLR9/RIG-I-induced cytokine production. In a placebo-controlled clinical study, these same endpoints were evaluated in healthy volunteers that were treated with a cumulative dose of 2400 mg HCQ over 5 days. In vitro, HCQ inhibited TLR responses with IC
    MeSH term(s) Humans ; Hydroxychloroquine/pharmacology ; Hydroxychloroquine/therapeutic use ; Pharmacology, Clinical ; Toll-Like Receptor 7 ; Toll-Like Receptor 9 ; Immunosuppression Therapy ; Cytokines
    Chemical Substances Hydroxychloroquine (4QWG6N8QKH) ; Toll-Like Receptor 7 ; Toll-Like Receptor 9 ; Cytokines
    Language English
    Publishing date 2023-02-22
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 632857-x
    ISSN 1559-0755 ; 0257-277X
    ISSN (online) 1559-0755
    ISSN 0257-277X
    DOI 10.1007/s12026-023-09367-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1755: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll-Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells.

    Grievink, Hendrika W / Jirka, Silvana M G / Woutman, Tess D / Schoonakker, Mascha / Rissmann, Robert / Malone, Karen E / Feiss, Gary / Moerland, Matthijs

    Clinical and translational science

    2020  Volume 13, Issue 5, Page(s) 891–895

    Abstract: LL-37 is a cationic antimicrobial peptide and the sole human member of cathelicidins. Besides its bactericidal properties, LL-37 is known to have direct immunomodulatory effects, among which enhancement of antiviral responses via endosomal toll-like ... ...

    Abstract LL-37 is a cationic antimicrobial peptide and the sole human member of cathelicidins. Besides its bactericidal properties, LL-37 is known to have direct immunomodulatory effects, among which enhancement of antiviral responses via endosomal toll-like receptors (TLRs). Omiganan pentahydrochloride is a synthetic cationic peptide in clinical development. Previously, omiganan was primarily known for its direct bactericidal and antifungal properties. We investigated whether omiganan enhances endosomal TLR responses, similar to LL-37. Human peripheral blood mononuclear cells were treated with endosomal TLR3, -7, -8, and -9 ligands in the presence of omiganan. Omiganan enhanced TLR-mediated interferon-α release. Subsequent experiments with TLR9 ligands showed that plasmacytoid dendritic cells were main contributors to omiganan-enhanced IFN production. Based on this type I interferon-enhancing effect, omiganan may qualify as potential treatment modality for virus-driven diseases. The molecular mechanism by which omiganan enhances endosomal TLR responses remains to be elucidated.
    MeSH term(s) Anti-Infective Agents/pharmacology ; Antimicrobial Cationic Peptides/pharmacology ; Cells, Cultured ; Dendritic Cells ; Drug Evaluation, Preclinical ; Endosomes/drug effects ; Endosomes/immunology ; Endosomes/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Healthy Volunteers ; Humans ; Interferon-alpha/analysis ; Interferon-alpha/metabolism ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Ligands ; Male ; Primary Cell Culture ; Signal Transduction/drug effects ; Signal Transduction/immunology ; Toll-Like Receptors/metabolism
    Chemical Substances Anti-Infective Agents ; Antimicrobial Cationic Peptides ; Interferon-alpha ; Ligands ; Toll-Like Receptors ; omiganan pentahydrochloride (LX2P9RD54V)
    Language English
    Publishing date 2020-04-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2433157-0
    ISSN 1752-8062 ; 1752-8054
    ISSN (online) 1752-8062
    ISSN 1752-8054
    DOI 10.1111/cts.12789
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: An autopsy study suggests that diabetic nephropathy is underdiagnosed.

    Klessens, Celine Q F / Woutman, Tess D / Veraar, Kimberley A M / Zandbergen, Malu / Valk, Elisabeth J J / Rotmans, Joris I / Wolterbeek, Ron / Bruijn, Jan A / Bajema, Ingeborg M

    Kidney international

    2016  Volume 90, Issue 1, Page(s) 149–156

    Abstract: The reported prevalence of diabetic nephropathy (DN) among patients with diabetes varies widely. Most studies use the presence of microalbuminuria for clinical onset of DN in the absence of a histopathologic evaluation. In this autopsy study, we ... ...

    Abstract The reported prevalence of diabetic nephropathy (DN) among patients with diabetes varies widely. Most studies use the presence of microalbuminuria for clinical onset of DN in the absence of a histopathologic evaluation. In this autopsy study, we collected and analyzed data from a cohort of patients with type 1 or 2 diabetes and determined the prevalence of histologically proven DN in patients with or without clinical manifestations of renal disease. We also examined the distribution among histopathologic classes with respect to clinical parameters. Renal tissue specimens from autopsies and clinical data were collected retrospectively from 168 patients with diabetes. The histopathologic classification for DN was scored as were interstitial and vascular parameters. In this cohort, 106 of 168 patients had histopathologic changes in the kidney characteristic of DN. Twenty of the 106 histologically proven DN cases did not present with DN-associated clinical manifestations within their lifetime. Glomerular and interstitial lesions were associated with renal function but not with proteinuria. We also found that underdiagnosed DN may encompass all histopathologic classes except the sclerotic class. Thus, the prevalence of histologically proven DN was higher than previously appreciated, and we found a relatively high proportion of DN that was clinically underdiagnosed yet histologically proven, suggesting that DN lesions may develop before the onset of clinical findings.
    MeSH term(s) Aged ; Albuminuria/diagnosis ; Biopsy ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 2/complications ; Diabetic Nephropathies/diagnosis ; Diabetic Nephropathies/epidemiology ; Diabetic Nephropathies/pathology ; Female ; Humans ; Kidney Glomerulus/pathology ; Male ; Prevalence ; Prognosis ; Retrospective Studies ; Risk Factors
    Language English
    Publishing date 2016-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2016.01.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 797: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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