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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 trantransplantation 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-resiresistant 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-resiresistant 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, Ricardo Augusto Dias, Roberto G. S. Berlinck, Antonio G Ferreira, L V Costa, Marisa Rangel, E L A Malpezzi, J C De Freitas, 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 stimstimulation 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.