The Experts below are selected from a list of 66 Experts worldwide ranked by ideXlab platform

Paul L Bollyky - One of the best experts on this subject based on the ideXlab platform.

  • hyaluronan synthesis is necessary for autoreactive t cell trafficking activation and th1 polarization
    Proceedings of the National Academy of Sciences of the United States of America, 2016
    Co-Authors: Hedwich F Kuipers, Nadine Nagy, Thomas N Wight, Mary Rieck, Irina Gurevich, Manish J Butte, Robert S Negrin, Lawrence Steinman, Paul L Bollyky
    Abstract:

    The extracellular matrix polysaccharide hyaluronan (HA) accumulates at sites of autoimmune inflammation, including white matter lesions in multiple sclerosis (MS), but its functional importance in pathogenesis is unclear. We have evaluated the impact of 4-methylumbelliferone (4-MU), an oral inhibitor of HA synthesis, on disease progression in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Treatment with 4-MU decreases the incidence of EAE, delays its onset, and reduces the severity of established disease. 4-MU inhibits the activation of autoreactive T cells and prevents their polarization toward a Th1 phenotype. Instead, 4-MU promotes polarization toward a Th2 phenotpye and induction of Foxp3(+) regulatory T cells. Further, 4-MU hastens trafficking of T cells through secondary lymphoid organs, impairs the infiltration of T cells into the CNS parenchyma, and limits astrogliosis. Together, these data suggest that HA synthesis is necessary for disease progression in EAE and that treatment with 4-MU may be a potential therapeutic strategy in CNS autoimmunity. Considering that 4-MU is already a therapeutic, called Hymecromone, that is approved to treat biliary spasm in humans, we propose that it could be repurposed to treat MS.

  • 4 methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation autoimmunity and cancer
    Frontiers in Immunology, 2015
    Co-Authors: Nadine Nagy, Hedwich F Kuipers, Adam Frymoyer, Heather D Ishak, Jennifer B Bollyky, Thomas N Wight, Paul L Bollyky
    Abstract:

    Hyaluronan (HA) is a prominent component of the extracellular matrix at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis, and numerous malignancies. Recent publications have demonstrated that when HA synthesis is inhibited using 4-methylumbelliferone (4-MU), beneficial effects are observed in several animal models of these diseases. Notably, 4-MU is an already approved drug in Europe and Asia called "Hymecromone" where it is used to treat biliary spasm. However, there is uncertainty regarding how 4-MU treatment provides benefit in these animal models and the potential long-term consequences of HA inhibition. Here, we review what is known about how HA contributes to immune dysregulation and tumor progression. Then, we review what is known about 4-MU and Hymecromone in terms of mechanism of action, pharmacokinetics, and safety. Finally, we review recent studies detailing the use of 4-MU to treat animal models of cancer and autoimmunity.

  • 4-Methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation, autoimmunity, and cancer
    Frontiers Media S.A., 2015
    Co-Authors: Nadine Enagy, Hedwich F Kuipers, Adam Frymoyer, Heather D Ishak, Jennifer B Bollyky, Thomas N Wight, Paul L Bollyky
    Abstract:

    Hyaluronan (HA) is a prominent component of the extracellular matrix (ECM) at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis (MS), and numerous malignancies. Recent publications have demonstrated that when HA synthesis is inhibited using 4-methylumbelliferone (4-MU) beneficial effects are observed in several animal models of these diseases. Notably, 4-MU is an already approved drug in Europe and Asia called Hymecromone where it is used to treat biliary spasm. However, there is uncertainty regarding how 4-MU treatment provides benefit in these animal models and the potential long-term consequences of HA inhibition. Here, we review what is known about how HA contributes to immune dysregulation and tumor progression. Then, we review what is known about 4-MU and Hymecromone in terms of mechanism of action, pharmacokinetics, and safety. Finally, we review recent studies detailing the use of 4-MU to treat animal models of cancer and autoimmunity

Margarita Karaivanova - One of the best experts on this subject based on the ideXlab platform.

  • new lanthanide complexes of 4 methyl 7 hydroxycoumarin and their pharmacological activity
    European Journal of Medicinal Chemistry, 2001
    Co-Authors: Irena Kostova, Ilia Manolov, Irina Nicolova, Spiro Konstantinov, Margarita Karaivanova
    Abstract:

    Abstract Complexes of cerium(III), lanthanum(III) and neodymium(III) with 4-methyl-7-hydroxycoumarin (Mendiaxon, Hymecromone) were synthesized by the mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1 H and 13 C NMR spectroscopies and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity. The complexes of cerium(III) and neodymium(III) showed marginal cytotoxic activity against transformed leukemic cell lines (P3HR1 and THP-1) as compared to the inorganic salts.

Irena Kostova - One of the best experts on this subject based on the ideXlab platform.

  • new metal complexes of 4 methyl 7 hydroxycoumarin sodium salt and their pharmacological activity
    Farmaco, 2001
    Co-Authors: Irena Kostova, Ilia Manolov, Irina Nicolova, Nicolay D Danchev
    Abstract:

    Abstract Complexes of copper (II), zinc (II), nickel (II), cobalt (II) and iron (III) with 4-methyl-7-hydroxycoumarin sodium salt (Mendiaxon, Hymecromone) were synthesized by mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1 H NMR spectroscopy and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. Thermal analysis of the complexes indicate the formation of compounds which correspond to the compositions Met(HL) 2 · n H 2 O, where Met=Cu, Zn, Ni, Co; n =2, 3 or 4 and Fe(HL) 3 ·5H 2 O. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity.

  • new lanthanide complexes of 4 methyl 7 hydroxycoumarin and their pharmacological activity
    European Journal of Medicinal Chemistry, 2001
    Co-Authors: Irena Kostova, Ilia Manolov, Irina Nicolova, Spiro Konstantinov, Margarita Karaivanova
    Abstract:

    Abstract Complexes of cerium(III), lanthanum(III) and neodymium(III) with 4-methyl-7-hydroxycoumarin (Mendiaxon, Hymecromone) were synthesized by the mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1 H and 13 C NMR spectroscopies and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity. The complexes of cerium(III) and neodymium(III) showed marginal cytotoxic activity against transformed leukemic cell lines (P3HR1 and THP-1) as compared to the inorganic salts.

Ilia Manolov - One of the best experts on this subject based on the ideXlab platform.

  • new metal complexes of 4 methyl 7 hydroxycoumarin sodium salt and their pharmacological activity
    Farmaco, 2001
    Co-Authors: Irena Kostova, Ilia Manolov, Irina Nicolova, Nicolay D Danchev
    Abstract:

    Abstract Complexes of copper (II), zinc (II), nickel (II), cobalt (II) and iron (III) with 4-methyl-7-hydroxycoumarin sodium salt (Mendiaxon, Hymecromone) were synthesized by mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1 H NMR spectroscopy and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. Thermal analysis of the complexes indicate the formation of compounds which correspond to the compositions Met(HL) 2 · n H 2 O, where Met=Cu, Zn, Ni, Co; n =2, 3 or 4 and Fe(HL) 3 ·5H 2 O. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity.

  • new lanthanide complexes of 4 methyl 7 hydroxycoumarin and their pharmacological activity
    European Journal of Medicinal Chemistry, 2001
    Co-Authors: Irena Kostova, Ilia Manolov, Irina Nicolova, Spiro Konstantinov, Margarita Karaivanova
    Abstract:

    Abstract Complexes of cerium(III), lanthanum(III) and neodymium(III) with 4-methyl-7-hydroxycoumarin (Mendiaxon, Hymecromone) were synthesized by the mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1 H and 13 C NMR spectroscopies and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity. The complexes of cerium(III) and neodymium(III) showed marginal cytotoxic activity against transformed leukemic cell lines (P3HR1 and THP-1) as compared to the inorganic salts.

Irina Nicolova - One of the best experts on this subject based on the ideXlab platform.

  • new metal complexes of 4 methyl 7 hydroxycoumarin sodium salt and their pharmacological activity
    Farmaco, 2001
    Co-Authors: Irena Kostova, Ilia Manolov, Irina Nicolova, Nicolay D Danchev
    Abstract:

    Abstract Complexes of copper (II), zinc (II), nickel (II), cobalt (II) and iron (III) with 4-methyl-7-hydroxycoumarin sodium salt (Mendiaxon, Hymecromone) were synthesized by mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1 H NMR spectroscopy and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. Thermal analysis of the complexes indicate the formation of compounds which correspond to the compositions Met(HL) 2 · n H 2 O, where Met=Cu, Zn, Ni, Co; n =2, 3 or 4 and Fe(HL) 3 ·5H 2 O. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity.

  • new lanthanide complexes of 4 methyl 7 hydroxycoumarin and their pharmacological activity
    European Journal of Medicinal Chemistry, 2001
    Co-Authors: Irena Kostova, Ilia Manolov, Irina Nicolova, Spiro Konstantinov, Margarita Karaivanova
    Abstract:

    Abstract Complexes of cerium(III), lanthanum(III) and neodymium(III) with 4-methyl-7-hydroxycoumarin (Mendiaxon, Hymecromone) were synthesized by the mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1 H and 13 C NMR spectroscopies and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity. The complexes of cerium(III) and neodymium(III) showed marginal cytotoxic activity against transformed leukemic cell lines (P3HR1 and THP-1) as compared to the inorganic salts.