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Junichi Kobayashi - One of the best experts on this subject based on the ideXlab platform.

  • Pyrinodemins G–I, new bis-3-alkylpyridine alkaloids from a marine sponge Amphimedon sp.
    Tetrahedron, 2013
    Co-Authors: Takaaki Kubota, Kenichi Kura, Jane Fromont, Junichi Kobayashi
    Abstract:

    Three new bis-3-alkylpyridine alkaloids, pyrinodemins G–I (1–3), were isolated from an Okinawan marine sponge Amphimedon sp. and the structures of 1–3 were elucidated on the basis of spectroscopic data. Pyrinodemins G–I (1–3) were novel bis-3-alkylpyridine alkaloids possessing an N-methoxy amide moiety, an α,β-unsaturated 3,5-disubstituted γ-lactone moiety, and a 2,3-di-substituted acrolein at a junction of two 3-alkylpyridines, respectively. Pyrinodemins G (1) and H (2) showed cytotoxicity against P388 Murine leukemia cells.

  • pyrinodemins g i new bis 3 alkylpyridine alkaloids from a marine sponge amphimedon sp
    Tetrahedron, 2013
    Co-Authors: Takaaki Kubota, Kenichi Kura, Jane Fromont, Junichi Kobayashi
    Abstract:

    Three new bis-3-alkylpyridine alkaloids, pyrinodemins G–I (1–3), were isolated from an Okinawan marine sponge Amphimedon sp. and the structures of 1–3 were elucidated on the basis of spectroscopic data. Pyrinodemins G–I (1–3) were novel bis-3-alkylpyridine alkaloids possessing an N-methoxy amide moiety, an α,β-unsaturated 3,5-disubstituted γ-lactone moiety, and a 2,3-di-substituted acrolein at a junction of two 3-alkylpyridines, respectively. Pyrinodemins G (1) and H (2) showed cytotoxicity against P388 Murine leukemia cells.

  • pyrinodemins e and f new 3 alkylpyridine alkaloids from sponge amphimedon sp
    Bioorganic & Medicinal Chemistry Letters, 2011
    Co-Authors: Kenichi Kura, Takaaki Kubota, Jane Fromont, Junichi Kobayashi
    Abstract:

    Two new 3-alkylpyridine alkaloids, pyrinodemins E (1) and F (2), were isolated from an Okinawan marine sponge Amphimedon sp. and the structures of 1 and 2 were elucidated on the basis of spectroscopic data. Pyrinodemins E (1) and F (2) were novel 3-alkylpyridine alkaloids possessing a 4-(methoxyamino)piperidinone moiety and an indol-3-glyoxylamide moiety, respectively. Pyrinodemin E (1) showed cytotoxicity against P388 and L1210 Murine leukemia cells.

Kristen J Skvorak - One of the best experts on this subject based on the ideXlab platform.

  • hepatocyte transplantation htx corrects selected neurometabolic abnormalities in Murine intermediate maple syrup urine disease imsud
    Biochimica et Biophysica Acta, 2009
    Co-Authors: Kristen J Skvorak, Elizabeth J Hager, Erland Arning, Teodoro Bottiglieri, Harbhajan S Paul, Stephen C Strom, Gregg E Homanics, Erwin E W Jansen
    Abstract:

    Abstract Skvorak et al. [1] demonstrated the therapeutic efficacy of HTx in a Murine model of iMSUD, confirming significant metabolic improvement and survival. To determine the effect of HTx on extrahepatic organs, we examined the metabolic effects of HTx in brain from iMSUD animals. Amino acid analysis revealed that HTx corrected increased ornithine, partially corrected depleted glutamine, and revealed a trend toward alloisoleucine correction. For amino acid and monoamine neurotransmitters, decreased GABA was partially corrected with HTx, while the l -histidine dipeptide of GABA, homocarnosine, was decreased in iMSUD mice and hypercorrected following HTx. Elevated branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in MSUD can deplete brain tyrosine and tryptophan (the precursors of monoamine neurotransmitters, dopamine (DA) and serotonin (5-hydroxytryptamine; 5-HT)) through competition via the large neutral amino acid transporter. HTx corrected decreased DA levels and the DA metabolite, 3-methoxytyramine, and partially corrected the DA intermediate 3,4-dihydroxyphenylacetate (DOPAC) and 5-HT levels, despite normal tyrosine and tryptophan levels in iMSUD mouse brain. We further observed enhanced intracellular turnover of both DA and 5-HT in iMSUD mouse brain, both of which partially corrected with HTx. Our results suggest new pathomechanisms of neurotransmitter metabolism in this disorder and support the therapeutic relevance of HTx in iMSUD mice, while providing proof-of-principle that HTx has corrective potential in extrahepatic organs.

  • hepatocyte transplantation improves phenotype and extends survival in a Murine model of intermediate maple syrup urine disease
    Molecular Therapy, 2009
    Co-Authors: Kristen J Skvorak, Harbhajan S Paul, Gregg E Homanics, Kenneth Dorko, Fabio Marongiu, Ewa Ellis, Donald Chace, Carolyn Ferguson, Michael K Gibson, Stephen C Strom
    Abstract:

    Maple syrup urine disease (MSUD; OMIM 248600) is an inborn error of metabolism of the branched chain α-ketoacid dehydrogenase (BCKDH) complex that is treated primarily by dietary manipulation of branched-chain amino acids (BCAA). Dietary restriction is lifelong and compliance is difficult. Liver transplantation significantly improves outcomes; however, alternative therapies are needed. To test novel therapies such as hepatocyte transplantation (HTx), we previously created a Murine model of intermediate MSUD (iMSUD), which closely mimics human iMSUD. LacZ-positive Murine donor hepatocytes were harvested and directly injected (105 cells/50 µl) into liver of iMSUD mice (two injections at 1–10 days of age). Donor hepatocytes engrafted into iMSUD recipient liver, increased liver BCKDH activity, improved blood total BCAA/alanine ratio, increased body weight at weaning, and extended the lifespan of HTx-treated iMSUD mice compared to phosphate-buffered saline (PBS)–treated and untreated iMSUD mice. Based on these data demonstrating partial metabolic correction of iMSUD in a Murine model, coupled to the fact that multiple transplants are possible to enhance these results, we suggest that HTx represents a promising therapeutic intervention for MSUD that warrants further investigation.

Eduardo Hajdu - One of the best experts on this subject based on the ideXlab platform.

  • Antibiotic, cytotoxic and enzyme inhibitory activity of crude extracts from Brazilian marine invertebrates
    Revista Brasileira De Farmacognosia-brazilian Journal of Pharmacognosy, 2007
    Co-Authors: Mirna H. R. Seleghim, Eduardo Hajdu, Roberto G. S. Berlinck, Simone Possedente De Lira, M. H. Kossuga, Tatiana Batista, Guilherme Muricy, Rosana M. Rocha, Gislene G. F. Nascimento, Márcio Luis Andrade E Silva
    Abstract:

    Herein we present the results of a screening with 349 crude extracts of Brazilian marine sponges, ascidians, bryozoans and octocorals, against 16 strains of susceptible and antibiotic-resistant bacteria, one yeast (Candida albicans), Mycobacterium tuberculosis H37Rv, three cancer cell lines MCF-7 (breast), B16 (Murine melanoma ) and HCT8 (colon), and Leishmania tarentolae adenine phosphoribosyl transferase (L-APRT) enzyme. Less than 15% of marine sponge crude extracts displayed antibacterial activity, both against susceptible and antibiotic-resistant bacteria. Up to 40% of marine sponge crude extracts displayed antimycobacterial activity against M. tuberculosis H37Rv. Cytotoxicity was observed for 18% of marine sponge crude extracts. Finally, less than 3% of sponge extracts inhibited L-APRT. Less than 10% of ascidian crude extracts displayed antibacterial activity. More than 25% of ascidian crude extracts were active against M. tuberculosis and the three cancer cell lines. Only two crude extracts from the ascidian Polysyncraton sp. collected in different seasons (1995 and 1997) displayed activity against L-APRT. Less than 2% of bryozoan and octocoral crude extracts presented antibacterial activity, but a high percentage of crude extracts from bryozoan and octororal displayed cytotoxic (11% and 30%, respectively) and antimycobacterial (60%) activities. The extract of only one species of bryozoan, Bugula sp., presented inhibitory activity against L-APRT. Overall, the crude extracts of marine invertebrates herein investigated presented a high level of cytotoxic and antimycobacterial activities, a lower level of antibacterial activity and only a small number of crude extracts inhibited L-APRT. Taxonomic analysis of some of the more potently active crude extracts showed the occurrence of biological activity in taxa that have been previously chemically investigated. These include marine sponges belonging to genera Aaptos, Aplysina, Callyspongia, Haliclona, Niphates, Cliona, Darwinella, Dysidea, Ircinia, Monanchora and Mycale, ascidians of the genera Didemnum, Aplidium, Botrylloides, Clavelina, Polysyncraton and Symplegma, the bryozoan Bugula sp. and octocorals of the genera Carijoa and Lophogorgia. The subsequent chemical investigation of some of the active extracts led to the isolation of several new biologically active secondary metabolites. Our results are in agreement with previous screening programs carried out abroad, that showed a high percentage of bioactive extracts from Porifera, Ascidiacea, Cnidaria and Bryozoa.

  • 1 3 dimethylisoguanine a new purine from the marine sponge amphimedon viridis
    Journal of Natural Products, 1997
    Co-Authors: C C Chehade, Roberto G. S. Berlinck, E L A Malpezzi, L V Costa, J C De Freitas, Marisa Rangel, Ricardo Augusto Dias, Antonio G Ferreira, Eduardo Hajdu
    Abstract:

    A new purine, 1,3-dimethylisoguanine (1), has been isolated from the marine sponge Amphimedon viridis and identified by analysis of spectroscopic data. Compound 1 increased the contractions obtained by transmural electrical stimulation in the guinea pig longitudinal muscle/myenteric plexus in a dose-dependent manner.

Stephen C Strom - One of the best experts on this subject based on the ideXlab platform.

  • hepatocyte transplantation htx corrects selected neurometabolic abnormalities in Murine intermediate maple syrup urine disease imsud
    Biochimica et Biophysica Acta, 2009
    Co-Authors: Kristen J Skvorak, Elizabeth J Hager, Erland Arning, Teodoro Bottiglieri, Harbhajan S Paul, Stephen C Strom, Gregg E Homanics, Erwin E W Jansen
    Abstract:

    Abstract Skvorak et al. [1] demonstrated the therapeutic efficacy of HTx in a Murine model of iMSUD, confirming significant metabolic improvement and survival. To determine the effect of HTx on extrahepatic organs, we examined the metabolic effects of HTx in brain from iMSUD animals. Amino acid analysis revealed that HTx corrected increased ornithine, partially corrected depleted glutamine, and revealed a trend toward alloisoleucine correction. For amino acid and monoamine neurotransmitters, decreased GABA was partially corrected with HTx, while the l -histidine dipeptide of GABA, homocarnosine, was decreased in iMSUD mice and hypercorrected following HTx. Elevated branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in MSUD can deplete brain tyrosine and tryptophan (the precursors of monoamine neurotransmitters, dopamine (DA) and serotonin (5-hydroxytryptamine; 5-HT)) through competition via the large neutral amino acid transporter. HTx corrected decreased DA levels and the DA metabolite, 3-methoxytyramine, and partially corrected the DA intermediate 3,4-dihydroxyphenylacetate (DOPAC) and 5-HT levels, despite normal tyrosine and tryptophan levels in iMSUD mouse brain. We further observed enhanced intracellular turnover of both DA and 5-HT in iMSUD mouse brain, both of which partially corrected with HTx. Our results suggest new pathomechanisms of neurotransmitter metabolism in this disorder and support the therapeutic relevance of HTx in iMSUD mice, while providing proof-of-principle that HTx has corrective potential in extrahepatic organs.

  • hepatocyte transplantation improves phenotype and extends survival in a Murine model of intermediate maple syrup urine disease
    Molecular Therapy, 2009
    Co-Authors: Kristen J Skvorak, Harbhajan S Paul, Gregg E Homanics, Kenneth Dorko, Fabio Marongiu, Ewa Ellis, Donald Chace, Carolyn Ferguson, Michael K Gibson, Stephen C Strom
    Abstract:

    Maple syrup urine disease (MSUD; OMIM 248600) is an inborn error of metabolism of the branched chain α-ketoacid dehydrogenase (BCKDH) complex that is treated primarily by dietary manipulation of branched-chain amino acids (BCAA). Dietary restriction is lifelong and compliance is difficult. Liver transplantation significantly improves outcomes; however, alternative therapies are needed. To test novel therapies such as hepatocyte transplantation (HTx), we previously created a Murine model of intermediate MSUD (iMSUD), which closely mimics human iMSUD. LacZ-positive Murine donor hepatocytes were harvested and directly injected (105 cells/50 µl) into liver of iMSUD mice (two injections at 1–10 days of age). Donor hepatocytes engrafted into iMSUD recipient liver, increased liver BCKDH activity, improved blood total BCAA/alanine ratio, increased body weight at weaning, and extended the lifespan of HTx-treated iMSUD mice compared to phosphate-buffered saline (PBS)–treated and untreated iMSUD mice. Based on these data demonstrating partial metabolic correction of iMSUD in a Murine model, coupled to the fact that multiple transplants are possible to enhance these results, we suggest that HTx represents a promising therapeutic intervention for MSUD that warrants further investigation.

Kitao Fujiwara - One of the best experts on this subject based on the ideXlab platform.

  • study of in vitro cytotoxicity of arsenocholine a trimethyl arsenic compound in seafood
    Applied Organometallic Chemistry, 2002
    Co-Authors: Teruaki Sakurai, Chikara Kojima, Hidetoshi Kumata, Masayuki Ochiai, Kitao Fujiwara
    Abstract:

    We examined the in vitro cytotoxic effects of an organic arsenic compound contained in seafood, viz. the trimethyl (2-hydroxyethyl)-arsonium cation, or arsenocholine (AsCho), on some Murine immune effector cells, such as splenocytes, thymocytes, Peyer's patch lymphocytes, peritoneal macrophages and bone marrow (BM) cells using synthesized pure material. We found that AsCho had no cytotoxicity on most immune effector cells, even at concentrations over 10 mmol dm -3 , and it slightly but significantly enhanced the viability of BM cells at doses over 100 μmol dm -3 . This biological effect of AsCho on BM cells might be direct rather than due to autocrine mechanisms mediating some factors secreted by AsCho-stimulated BM cells, because the culture supernatants of BM cells pre-stimulated with AsCho did not influence the viability of other fresh BM cells. It is interesting that this unique biological effect was found in AsCho, an organic arsenic compound contained in some marine animals that are ingested daily as seafood in many countries.

  • cytotoxicological aspects of the organic arsenic compound arsenobetaine in marine animals
    Applied Organometallic Chemistry, 2002
    Co-Authors: Chikara Kojima, Teruaki Sakurai, Hidetoshi Kumata, Wei Qu, Michael P Waalkes, Masayuki Ochiai, Kitao Fujiwara
    Abstract:

    In this study, we investigated the in vitro cytotoxicity of arsenobetaine [AsBe; trimethyl (carboxymethyl) arsonium zwitterion], which is a major organic arsenic compound in marine animals, to various mammalian cells, such as mouse macrophage RAW264.7 cells, rat liver TRL1215 cells and human skin TIG-112 cells, using a synthetic pure material. As a result, we demonstrated that the cytotoxicity of AsBe is very weak even at concentrations over 20 mmol dm -3 in all these cells. Also, AsBe did not affect various functions of the Murine macrophage RAW264.7 cells, viz interleukin-1α production, cellular lysosomal enzyme (acid phosphatase) activity and nitric oxide (NO - 2 ) secretion. AsBe showed a weak effect on the reduced glutathione (GSH) levels in these cells, and it slightly reduced the cellular GSH levels for a while. These data suggest that AsBe shows no cytotoxicity but has some effects on mammalian cells.

  • modulation of cell adhesion and viability of cultured Murine bone marrow cells by arsenobetaine a major organic arsenic compound in marine animals
    British Journal of Pharmacology, 2001
    Co-Authors: Teruaki Sakurai, Kitao Fujiwara
    Abstract:

    In this study, we investigated the biological effects of trimethyl (carboxymethyl) arsonium zwitterion, namely arsenobetaine (AsBe), which is a major organic arsenic compound in marine animals using Murine bone marrow (BM) cells and compared them with those of an inorganic arsenical, sodium arsenite, in vitro. Sodium arsenite showed strong cytotoxicity in BM cells, and its IC50 was 6 μM. In contrast, AsBe significantly enhanced the viability of BM cells in a dose-dependent manner during a 72-h incubation; about a twofold increase in the viability of cells compared with that of control cells cultured with the medium alone was observed with a μM level of AsBe. In morphological investigations, AsBe enhanced the numbers of large mature adherent cells, especially granulocytes, during a 72-h BM culture. When BM cells were cultured together with AsBe and a low dose (1 u ml−1) of recombinant Murine granulocyte/macrophage colony-stimulating factor (rMu GM-CSF), significant additive-like increasing effects were observed on the numbers of both granulocytes and macrophages originated from BM cells. However, AsBe did not cause proliferation of BM cells at all as determined by colony-forming assay using a gelatious medium. These findings demonstrate the unique and potent biological effects in mammalian cells of AsBe, a major organic arsenic compound in various marine animals which are ingested daily as seafood in many countries. British Journal of Pharmacology (2001) 132, 143–150; doi:10.1038/sj.bjp.0703790