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  • American Diabetes Association  (2)
  • LEE, HAN SIN  (2)
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  • American Diabetes Association  (2)
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  • 1
    Online Resource
    Online Resource
    Protective Effect of NecroX-7 on Islets against Oxidative Stress and Inflammation
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Oxidative stress generated during islet isolation, culture, and transplantation causes islet cell damage mediated by hypoxia, reactive oxygen species (ROS) and inflammatory responses. We investigated the protective effects of NecroX-7, a novel ROS scavenger, during isolation and/or culture of islets. For ex vivo studies, islets from heterozygote human islet amyloid polypeptide (hIAPP+/-) mice and C57BL/6J mice were isolated by collagenase with and without supplementation with 20 uM of NecroX-7. Supplementation with NecroX-7 provided markedly increased islet viability and ATP contents, and attenuated ROS, transcription of c-Jun N-terminal kinases, high mobility group box-1 (HMGB1) and proinflammatory cytokines including interleukin-1beta (IL-1b), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-a). Transplantation of islets, which is derived from islet isolation method using supplementation with NecroX-7, into syngeneic subrenal subcapsular of hIAPP+/- mice also improved post-transplant blood glucose levels. Also, NecroX-7 protected RINm5F cells from t-BHP-induced and serum deprivation induced toxicity in in vitro culture by dose-dependent manner from 0.1 uM to 20 uM. Supplementation of medium with NecroX-7 during serum-deprived culture condition also improved impaired viability and serum deprivation-induced ROS in islets from hIAPP+/- mice by dose-dependent manner from 0.1 uM to 20 uM. These findings suggest that NecroX-7 supplementation during the islet isolation and/or culture process suppressed inflammatory responses and ROS induced by serum deprivation and provides a potential benefit to improve post-transplantation outcomes. Disclosure Y. Kwon: None. H. Lee: None. H. Kim: None. G. Kim: None. S. Jin: None. M. Lee: None. J. Kim: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1744-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Synergistic Effect of Islet Magnetic Resonance Imaging Using Direct Linking of Ferumoxytol to Surface of PEGylated Islet
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Purpose: We previously reported the feasibility of islet magnetic resonance imaging (MRI) using ferumoxytol, which is the only clinically-available ultrasmall superparamagnetic iron oxide. However, the labeling efficacy was not sufficient for its clinical use in islet transplantation. We aimed to evaluate the feasibility of islet MRI using direct linking of ferumoxytol to islet surface through PEGylation. Method: Islets were labeled by surface modification with up to 4% PEG-heparin-ferumoxytol. We compared islet function and viability of control islets and ferumoxytol-heparin-PEGylated islets. Efficacy of labeling with ferumoxytol-heparin-PEGylation and ferumoxytol alone was assessed in both ex vivo and in vivo models. Results: Labeling of islets with up to 2% PEG-heparin-ferumoxytol did not derange ex vivo islet viability and function. The T2* relaxation time was optimal when islets were labeled with 1 to 4% PEG-heparin-ferumoxytol. The labeling intensity in the ex vivo MRI of ferumoxytol-heparin-PEGylated islets was stronger than islets labeled with ferumoxytol alone. In syngeneic renal subcapsular islet transplantation, labeling with ferumoxytol-heparin-PEGylation showed better in vivo labeling efficacy than that of islets labeled with ferumoxytol alone. After labeling with ferumoxytol-heparin-PEGylation, there was a correlation between the total area of visualized islets and the transplanted islet mass in syngeneic mouse intraportal islet transplantation, and the visibility was also confirmed in the preliminary analysis of non-human primate intraportal islet transplantation model. Conclusion: Direct linking of ferumoxytol to islet surface through PEGylation improved the labeling efficacy and it could be used for the islet MRI in clinical islet transplantation. Disclosure H. Lee: None. Y. Kwon: None. H. Kim: None. M.R. Haque: None. G. Kim: None. S. Jin: None. M. Lee: None. Y. Byun: None. J. Kim: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1745-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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