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  • 1
    Electronic Resource
    Electronic Resource
    Xenografts of porcine islets immunoprotected in hollow fibres reduce the incidence of diabetes in non-obese diabetic mice (1996)
    Springer
    Diabetologia 39 (1996), S. 523-529 
    Details
    ISSN: 1432-0428
    Keywords: Keywords NOD mouse ; prevention ; diabetes mellitus ; porcine islets ; xenograft ; hollow fibres.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-obese diabetic (NOD) mice develop an autoimmune disease with a long prodromal period and constitute a model for investigating the prevention of human insulin-dependent diabetes mellitus. Since insulin injected prophylactically has been shown to reduce incidence of diabetes in NOD mice, we tested a new strategy consisting of prophylactic xenografts of porcine pancreatic islets immunoprotected in semipermeable hollow fibres. Female NOD mice were transplanted twice (at 60 and 180 days of age) with islet-containing or empty fibres. Within the group grafted with protected islets, the incidence of diabetes was reduced (37 vs 75 %; p 〈 0.01), the onset of disease was delayed (p 〈 0.02), and the severity of lymphocytic inflammation of endogenous islets was reduced (p 〈 0.02). When already diabetic mice were not taken into account for analysis, blood glucose level was slightly lower in those grafted with islet-containing fibres (p 〈 0.04). Graft function was also evidenced by HPLC separation of porcine insulin in NOD sera. Histological and perifusion studies of fibres retrieved from recipients confirmed immunoprotection. During co-transfer, T splenocytes from mice grafted with islet-containing fibres were able to reduce the capacity of T cells from diabetic donors to adoptively transfer the disease (p 〈 0.01). Antigens for islet-cell autoantibodies (ICA) in pancreata from both groups were compared by immunofluorescence with the same ICA-positive human sera to ensure that differences were due to antigen quantitative changes. These antigens, which could serve as an index of a possibly more extensive antigen beta-cell rest, were decreased (p 〈 0.01) in mice grafted with protected islets. Reduction of diabetes and insulitis following early islet transplantation may thus be due to generation of cellular mechanisms that actively suppress disease, and possibly in part to a decrease in antigens which make beta cells less vulnerable to autoimmune aggression. These effects can be obtained with xenogeneic islets protected in hollow fibres, thereby eliminating the need for immunosuppression. Based on the concept of prophylactic insulin therapy, this form of insulin administration offers a controlled means of delivering insulin to meet the physiological needs of recipients. [Diabetologia (1996) 39: 523–529]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403298
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    High-performance liquid chromatography analysis of circulating insulins distinguishes between endogenous insulin production (a potential pitfall with streptozotocin diabetic rats) and islet xenograft function (1990)
    Springer
    Diabetologia 33 (1990), S. 457-461 
    Details
    ISSN: 1432-0428
    Keywords: Microencapsulated ; porcine ; islets ; streptozotocin ; diabetic rats ; pancreas regeneration ; bioartificial pancreas ; high performance liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Porcine islets of Langerhans were microencapsulated according to the alginate-polylysine procedure, and implanted into the peritoneal cavity of 15 streptozotocin-induced (70 mg/kg) diabetic rats (6000 microencapsulated islets per rat). In four animals, a sustained decrease in plasma glucose level below 8.3 mmol/l was observed for up to nine months. However, it was possible to recover microcapsules from the peritoneal cavity of only one rat, and they were found to be damaged and containing no detectable tissue. When insulin in the plasma of three of these animals was analysed by reversed phase high-performance liquid chromatography, only rat insulins I and II, but not porcine insulin was detectable, indicating unambiguously that at the time of analysis, the correction of diabetes in these animals was due to the function of the recipient's own pancreas rather than the continued, long-term, function of the implanted porcine islets. These data confirm that in this model of diabetes, function of the host pancreas can resume following islet transplantation, leading in turn to the potential for a major bias in the interpretation of the data. In the case of an islet xenograft, when the donor's and recipient's insulins can be separated by highperformance liquid chromatography, this non-invasive analytical method should prove useful for identifying the source of insulin in the circulation, and thus the relative functional status of the endogenous and transplanted islets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405105
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Xenografts of porcine islets immunoprotected in hollow fibres reduce the incidence of diabetes in non-obese diabetic mice (1996)
    Springer
    Diabetologia 39 (1996), S. 523-529 
    Details
    ISSN: 1432-0428
    Keywords: NOD mouse ; prevention ; diabetes mellitus ; porcine islets ; xenograft ; hollow fibres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-obese diabetic (NOD) mice develop an autoimmune disease with a long prodromal period and constitute a model for investigating the prevention of human insulin-dependent diabetes mellitus. Since insulin injected prophylactically has been shown to reduce incidence of diabetes in NOD mice, we tested a new strategy consisting of prophylactic xenografts of porcine pancreatic islets immunoprotected in semipermeable hollow fibres. Female NOD mice were transplanted twice (at 60 and 180 days of age) with islet-containing or empty fibres. Within the group grafted with protected islets, the incidence of diabetes was reduced (37 vs 75%; p〈0.01), the onset of disease was delayed (p〈0.02), and the severity of lymphocytic inflammation of endogenous islets was reduced (p〈0.02). When already diabetic mice were not taken into account for analysis, blood glucose level was slightly lower in those grafted with islet-containing fibres (p〈0.04). Graft function was also evidenced by HPLC separation of porcine insulin in NOD sera. Histological and perifusion studies of fibres retrieved from recipients confirmed immunoprotection. During co-transfer, T splenocytes from mice grafted with islet-containing fibres were able to reduce the capacity of T cells from diabetic donors to adoptively transfer the disease (p〈0.01). Antigens for islet-cell autoantibodies (ICA) in pancreata from both groups were compared by immunofluorescence with the same ICA-positive human sera to ensure that differences were due to antigen quantitative changes. These antigens, which could serve as an index of a possibly more extensive antigen beta-cell rest, were decreased (p〈0.01) in mice grafted with protected islets. Reduction of diabetes and insulitis following early islet transplantation may thus be due to generation of cellular mechanisms that actively suppress disease, and possibly in part to a decrease in antigens which make beta cells less vulnerable to autoimmune aggression. These effects can be obtained with xenogeneic islets protected in hollow fibres, thereby eliminating the need for immunosuppression. Based on the concept of prophylactic insulin therapy, this form of insulin administration offers a controlled means of delivering insulin to meet the physiological needs of recipients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403298
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Immunoisolation of pancreatic B cells by microencapsulation (1985)
    Springer
    Diabetologia 28 (1985), S. 776-780 
    Details
    ISSN: 1432-0428
    Keywords: Microencapsulation ; RINm5F cells ; complement fixing cytoxic antibodies ; immunoprotection ; bioartificial pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The selective permeability of alginate microcapsules, containing isolated rat islets of Langerhans or insulin secreting RINm5F cells, was investigated in vitro. An increase in insulin release was observed when microencapsulated islets were stimulated by glucose + theophylline, and when microencapsulated RINm5F cells were stimulated by arginine + theophylline. These findings demonstrate the permeability of the microcapsule membrane to these B-cell secretagogues and to insulin. Immunoisolation of RINm5F cells by microencapsulation was assessed using a 51chromium cytotoxicity test. Significant 51Cr release was observed when non-encapsulated cells were incubated with complement and either the serum of a rabbit immunized with RIN cells or the se ra of two patients with recently diagnosed Type 1 (insulin-dependent) diabetes. This effect was not observed with encapsulated cells. Both free and encapsulated cells released 80% of their initial radioactivity when incubated in the presence of HCl. These results clearly demonstrate pancreatic cell immunoisolation by microencapsulation. They also provide a method for the in vitro evaluation of the functional characteristics of microcapsules, in terms of both insulin permeability and immunoprotection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265027
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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