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  • 1.
    Dahlberg, Carina
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Physical Chemistry. KTH, School of Chemical Science and Engineering (CHE), Centres, Industrial NMR Centre.
    Millqvist-Fureby, Anna
    Schuleit, Michael
    Furó, István
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Physical Chemistry. KTH, School of Chemical Science and Engineering (CHE), Centres, Industrial NMR Centre.
    Relationships between solid dispersion preparation process, particle size and drug release: an NMR and NMR microimaging study2010In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 76, no 2, p. 311-319Article in journal (Refereed)
    Abstract [en]

    Solid dispersion tablets prepared by either spray drying or rotoevaporation and exhibiting different grain and pore sizes were investigated under the process of hydration-swelling-gelation. H-2 and H-1 NMR microimaging experiments were used to selectively follow water penetration and polymer mobilization kinetics, respectively, while the drug release kinetics was followed by H-1 NMR spectroscopy. The obtained data, in combination with morphological information by scanning electron microscopy (SEM), reveal a complex process that ultimately leads to release of the drug into the aqueous phase. We find that the rate of water ingress has no direct influence on release kinetics, which also renders air in the tablets a secondary factor. On the other hand, drug release is directly correlated with the polymer mobilization kinetics. Water diffusion into the originally dry polymer grains determines the rate of grain swelling and the hydration within the grains varies strongly with grain size. We propose that this sets the stage for creating homogeneous gels for small grain sizes and heterogeneous gels for large grain sizes. Fast diffusion through water-rich sections of the inhomogeneous gels that exhibit a large mesh size is the factor which yields a faster drug release from tablets prepared by rotoevaporation.

  • 2. El-Seedi, H. R.
    et al.
    El-Barbary, M. A.
    El-Ghorab, D. M. H.
    Bohlin, L.
    Borg-Karlson, Anna-Karin
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Goransson, U.
    Verpoorte, R.
    Recent Insights into the Biosynthesis and Biological Activities of Natural Xanthones2010In: Current Medicinal Chemistry, ISSN 0929-8673, E-ISSN 1875-533X, Vol. 17, no 9, p. 854-901Article in journal (Refereed)
    Abstract [en]

    This review focuses on recent advances in our understanding of the complex biosynthetic pathways and diverse biological activities of naturally occurring xanthones. The biosynthesis section covers studies published from 1989 to 2008 on xanthone production in plants and fungi, while the bioactivity review presents tabulated activities of more than 250 xanthones described in studies published from 2001 to 2008, together with structural information and indications of their wide-ranging potential uses as pharmacological tools. A large number of relevant papers have been published on these subjects (128 cited here), illustrating the diversity of the xanthones and their possible uses.

  • 3. El-Seedi, Hesham R.
    et al.
    El-Shabasy, Rehan
    Sakr, Hanem
    Zayed, Mervat
    El-Said, Asmaa M. A.
    Helmy, Khalid M. H.
    Gaara, Ahmed H. M.
    Turki, Zaki
    Azeem, Muhammad
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Ahmed, Ahmed M.
    Boulos, Loutfy
    Borg-Karlson, Anna-Karin
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Göransson, Ulf
    Anti-schistosomiasis triterpene glycoside from the Egyptian medicinal plant Asparagus stipularis2011In: REV BRAS FARMACOGN, ISSN 0102-695X, Vol. 22, no 2, p. 314-318Article in journal (Refereed)
    Abstract [en]

    Bioassay-guided isolation using an in vitro assay testing for anti-schistosomiasis yielded a novel triterpene saponin, asparagalin A, from the n-butanol extract of the roots of Asparagus stipularis Forssk., Asparagaceae. The structure was elucidated by spectroscopic analysis and chemical transformations. Administration of asparagalin A resulted in a retardation of worm growth and locomotion at the first day and showed a significant activity of egg-laying suppression at 200 mu g/mL concentration.

  • 4. García-Gallego, Sandra
    et al.
    Díaz, L.
    Jiménez, J. L.
    Gómez, R.
    De La Mata, F. J.
    Muñoz-Fernández, M. A.
    HIV-1 antiviral behavior of anionic PPI metallo-dendrimers with EDA core2015In: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 98, p. 139-148Article in journal (Refereed)
    Abstract [en]

    The development of novel strategies to prevent HIV-1 infection is of outstanding relevance. Metal complexes of Cu2+, Ni2+, Co2+ and Zn2+ derived from sulfonated and carboxylated poly(propylene imine) dendrimers with ethylenediamine core were evaluated as tunable antiviral agents against HIV-1. After demonstrating their biocompatibility, specific trends in the antiviral properties were found, related to both the dendritic scaffold (peripheral group, generation) and the bound metal ions (sort, amount). In HEC-1A and VK-2 cell lines, as model of the first barrier against HIV-1 infection, a high preventive inhibitory action was found, which also avoided virus internalization inside cells and inhibited both CCR5 and CXCR4 HIV-1 strains. In peripheral blood mononuclear cells (PBMC), as model of the second barrier, a dual preventive and therapeutic behavior was observed. A rational design of such metallodendrimers opens new avenues for the production of versatile and efficient treatments against HIV-1 infection.

  • 5. Hamngren Blomqvist, Charlotte
    et al.
    Dinér, Peter
    Department of Chemistry – BMC, Uppsala university.
    Grøtli, Morten
    Goksör, Mattias
    Adiels, Caroline B.
    Hamngren, C.
    Design and evaluation of a microfluidic system for inhibition studies of yeast cell signaling2012In: Proceedings of SPIE: Optical Trapping and Optical Micromanipulation IX / [ed] Kishan Dholakia and Gabriel C. Spalding, SPIE - International Society for Optical Engineering, 2012, Vol. 8458, p. 84582K-Conference paper (Refereed)
    Abstract [en]

    In cell signaling, different perturbations lead to different responses and using traditional biological techniques that result in averaged data may obscure important cell-to-cell variations. The aim of this study was to develop and evaluate a four-inlet microfluidic system that enables single-cell analysis by investigating the effect on Hog1 localization post a selective Hog1 inhibitor treatment during osmotic stress. Optical tweezers was used to position yeast cells in an array of desired size and density inside the microfluidic system. By changing the flow rates through the inlet channels, controlled and rapid introduction of two different perturbations over the cell array was enabled. The placement of the cells was determined by diffusion rates flow simulations. The system was evaluated by monitoring the subcellular localization of a fluorescently tagged kinase of the yeast “High Osmolarity Glycerol” (HOG) pathway, Hog1-GFP. By sequential treatment of the yeast cells with a selective Hog1 kinase inhibitor and sorbitol, the subcellular localization of Hog1-GFP was analysed on a single-cell level. The results showed impaired Hog1-GFP nuclear localization, providing evidence of a congenial design. The setup made it possible to remove and add an agent within 2 seconds, which is valuable for investigating the dynamic signal transduction pathways and cannot be done using traditional methods. We are confident that the features of the four-inlet microfluidic system will be a valuable tool and hence contribute significantly to unravel the mechanisms of the HOG pathway and similar dynamic signal transduction pathways.

  • 6.
    Hofström, Camilla
    et al.
    KTH, School of Biotechnology (BIO), Protein Technology.
    Altai, Mohamed
    Honarvar, Hadis
    Strand, Joanna
    Malmberg, Jennie
    Hosseinimehr, Seyed Jalal
    Orlova, Anna
    Gräslund, Torbjörn
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tolmachev, Vladimir
    HAHAHA, HEHEHE, HIHIHI, or HKHKHK: Influence of Position and Composition of Histidine Containing Tags on Biodistribution of [Tc-99m(CO)(3)](+)-Labeled Affibody Molecules2013In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 56, no 12, p. 4966-4974Article in journal (Refereed)
    Abstract [en]

    Engineered affibody molecules can be used for high contrast in vivo molecular imaging. Extending a recombinantly produced HER2 binding affibody molecule with a hexa-histidine tag allows for convenient purification by immobilized metal-ion affinity chromatography and labeling with [Tc-99m(CO)(3)](+) but increases radioactivity uptake in the liver. To investigate the impact of charge, lipophilicity, and position on biodistribution, 10 variants of a histidine-based tag was attached to a HER2 binding affibody molecule. The biochemical properties and the HER2 binding affinity appeared to be similar for all variants. In vivo, positive charge promoted liver uptake. For N-terminally placed tags, promoted liver uptake and decreased kidney uptake. Kidney uptake was higher for C-terminally placed tags compared to their N-terminal counterparts. The variant with the amino acid composition HEHEHE placed in the N-terminus gave the lowest nonspecific uptake.

  • 7.
    Hsieh, Yves S. Y.
    et al.
    University of Sydney, Australia.
    Taleski, Deni
    Wilkinson, Brendan L.
    Wijeyewickrema, Lakshmi C.
    Adams, Ty. E.
    Pike, Robert N.
    Payne, Richard J.
    Effect of O-glycosylation and tyrosine sulfation of leech-derived peptides on binding and inhibitory activity against thrombin2012In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 48, no 10, p. 1547-9Article in journal (Refereed)
    Abstract [en]

    Synthesis of sulfated and unsulfated (glyco)peptide fragments of Hirudin P6 (a potent anticoagulant from the leech Hirudinaria manillensis) is described. The effect of O-glycosylation and tyrosine sulfation on thrombin binding and peptidolytic activity was investigated, together with the inhibition of fibrinogen cleavage.

  • 8.
    Hsieh, Yves S-Y
    et al.
    Academia Sinica, Taiwan.
    Chien, Cheng
    Liao, Sylvian K-S
    Liao, Shih-Fen
    Hung, Wei-Ting
    Yang, Wen-Bin
    Lin, Chih-Chien
    Cheng, Ting-Jen Rachel
    Chang, Chia-Chuan
    Fang, Jim-Min
    Wong, Chi-Huey
    Structure and bioactivity of the polysaccharides in medicinal plant Dendrobium huoshanense2008In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 16, no 11, p. 6054-68Article in journal (Refereed)
    Abstract [en]

    Detailed structures of the active polysaccharides extracted from the leaf and stem cell walls and mucilage of Dendrobium huoshanense are determined by using various techniques, including chromatographic, spectroscopic, chemical, and enzymatic methods. The mucilage polysaccharide exhibits specific functions in activating murine splenocytes to produce several cytokines including IFN-gamma, IL-10, IL-6, and IL-1alpha, as well as hematopoietic growth factors GM-CSF and G-CSF. However, the deacetylated mucilage obtained from an alkaline treatment fails to induce cytokine production. The structure and bioactivity of mucilage components are validated by further fractionation. This is the first study that provides clear evidence for the structure and activity relationship of the polysaccharide in D. huoshanense.

  • 9. Nordström, Helena
    et al.
    Winquist, Johan
    Geitmann, Matthis
    Solbak, Sara
    Homan, Evert
    Dinér, Peter
    Hämäläinen, Markku
    Danielson, Helena
    Identification of Fragments for Design of HIV-1 Protease Inhibitors with Allosteric Mechanisms and New Resistance ProfilesManuscript (preprint) (Other academic)
  • 10.
    Ti, Huihui
    et al.
    Guangzhou Med Univ, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Sch Pharmaceut Sci, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China..
    Zhou, Yang
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Theoretical Chemistry and Biology. Guangzhou Med Univ, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Sch Pharmaceut Sci, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.
    Liang, Xue
    Guangzhou Med Univ, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Sch Pharmaceut Sci, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China..
    Li, Runfeng
    Guangzhou Med Univ, State Key Lab Resp Dis, Natl Clin Res Ctr Resp Dis, Guangzhou Inst Resp Hlth,Affiliated Hosp 1, Guangzhou 510120, Guangdong, Peoples R China..
    Ding, Ke
    Jinan Univ, Int Cooperat Lab Tradit Chinese Med Modernizat &, Chinese Minist Educ MOE, Sch Pharm,Guangzhou City Key Lab Precis Chem Drug, Guangzhou 510632, Guangdong, Peoples R China.;Guangzhou Med Univ, State Key Lab Resp Dis, Natl Clin Res Ctr Resp Dis, Guangzhou Inst Resp Hlth,Affiliated Hosp 1, Guangzhou 510120, Guangdong, Peoples R China..
    Zhao, Xin
    Guangzhou Med Univ, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Sch Pharmaceut Sci, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.;Chinese Univ Hong Kong, Sch Life Sci, Shatin, Hong Kong 999077, Peoples R China..
    Targeted Treatments for Chronic Obstructive Pulmonary Disease (COPD) Using Low-Molecular-Weight Drugs (LMWDs)2019In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 62, no 13, p. 5944-5978Article in journal (Refereed)
    Abstract [en]

    Chronic obstructive pulmonary disease (COPD) is a very common and frequently fatal airway disease. Current therapies for COPD depend mainly on long-acting bronchodilators, which cannot target the pathogenic mechanisms of chronic inflammation in COPD. New pharmaceutical therapies for the inflammatory processes of COPD are urgently needed. Several anti-inflammatory targets have been identified based on increased understanding of the pathogenesis of COPD, which raises new hopes for targeted treatment of this fatal respiratory disease. In this review, we discuss the recent advances in bioactive low-molecular-weight drugs (LMWDs) for the treatment of COPD and, in addition to the first-line drug bronchodilators, focus particularly on low-molecular-weight anti-inflammatory agents, including modulators of inflammatory mediators, inflammasome inhibitors, protease inhibitors, antioxidants, PDE4 inhibitors, kinase inhibitors, and other agents. We also provide new insights into targeted COPD treatments using LMWDs, particularly small-molecule agents.

  • 11. Wong, C. H.
    et al.
    Yang, W. B.
    Cheng, T. J.
    Hsieh, Yves S. Y.
    Chien, C.
    Lin, C. C.
    Wen, H. Y.
    Fang, J. M.
    Structure and bioactivity of the polysaccharides and oligomers in medicinal plant Dendrobium huoshanense2009Patent (Other (popular science, discussion, etc.))
  • 12. Yoshimura, T.
    et al.
    Narumi, M.
    Yagi, H.
    Kitamura, K.
    Sedzik, Jan
    KTH, School of Biotechnology (BIO).
    Kato, K.
    Ikenaka, K.
    STRUCTURE DETERMINATION OF N-GLYCANS ON A FEW PMOL GLYCOPROTEIN AND ITS APPLICATION TO THE STRUCTURAL ANALYSIS OF N-GLYCANS ON P02011In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 118, p. 150-150Article in journal (Other academic)
1 - 12 of 12
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