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  • 1
    ISSN: 1432-0428
    Keywords: Microencapsulation ; interleukin-1β ; pancreatic islets ; biocompatibility ; transplantation ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alginate-polylysine microencapsulation has been proposed as a method of protecting transplanted pancreatic islets against immunological attack. Using this technique, prolonged graft survival has been reported in some diabetic animals. However, in the spontaneously diabetic insulindependent BB/E rat we found that intraperitoneal implantation of microencapsulated islets had only a short-lived effect on hyperglycaemia. Recovered microcapsules (both those implanted empty and containing islets) were surrounded by a foreign body type cellular overgrowth and, although many capsules remained intact, encapsulated islets were observed to be disintegrating. Loss of Beta cells was confirmed by immunohistology. Various polymer materials used in artificial membranes have been shown to activate macrophages involved in foreign body reactions and induce synthesis of interleukin-1β, a known Beta-cell toxin. Reduced secretion of insulin and progressive islet damage (indicated by a significant reduction in residual islet insulin and DNA content) were demonstrated when microencapsulated islets were incubated with interleukin-1βin vitro for 9 days. Similar effects were seen following exposure to a combination of gamma interferon and alpha tumour necrosis factor. Successful use of microencapsulation in islet transplantation depends upon the development of biocompatible membranes. The exclusion of smaller molecules, such as cytokines, which may be involved in foreign body mediated damage and microencapsulated islet graft rejection, could also be important.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Key words IDDM, biopterin, pre-diabetes, nitric oxide, macrophages, insulitis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tetrahydrobiopterin (BH4) is a pteridine product which is released by rodent macrophages on activation by cytokines. We have used serial pancreatic biopsy, and measurement of serum biopterin at 30, 60, 90 and 120 days in the BB/S rat to relate histological change to macrophage activation during the course of pre-diabetes. Using immunohistochemistry, and an arbitrary scoring system read blind and standardised against day 30, we found that pancreatic MHC class I, MHC class II and infiltrating macrophage staining were upregulated in the BB/S diabetes-prone rats (n=17) at day 60, markedly so at day 90, and less so at day 120. Staining for resident pancreatic macrophages remained unchanged throughout in diabetes prone, diabetes resistant and Wistar (n=28) control animals. Serum biopterin fell progressively and identically with age in BB diabetes resistant rats (n=11) and Wistar controls. No change in weight gain or biopterin levels was observed in the biopsied animals. Mean serum biopterin levels in diabetes prone rats (of which 13 of 17 became diabetic at median 85 days) were the same as in diabetes resistant and Wistar rats at days 30, 60 and 120, but showed a striking and highly significant elevation (p〈0.001) at day 90. Although macrophages infiltrate the islet early in pre-diabetes, the timing of their activation is unknown. The rise in biopterin we observed is a potentially important immunological event which occurred late in the progression of pre-diabetes. This acute terminal event has not been reported previously, and may modify current concepts concerning the tempo of cell destruction during pre-diabetes. [Diabetologia (1994) 37: 466–470]
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  • 3
    ISSN: 1573-4838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Tolerance to alginate-polylysine-alginate microcapsules implanted into the peritoneal cavity was compared in the Wistar Furth rat and the BB/E (Wistar-derived) spontaneously diabetic rat. A marked foreign-body type reaction was observed in the BB/E rat in both diabetic and non-diabetic animals. In contrast, little or no reaction was observed in the Wistar Furth rat. Implantation under the kidney capsule, an immunologically privileged site, did not protect the microcapsules. Blocking the surface charge of the microcapsule by coating with tolylene diisocyanate also failed to modify the reaction. Coating with a water-insoluble lacquer (Eudragit RL) resulted in dense capsule overgrowth. Thus tolerance to alginate-polylysine-alginate microcapsules appears to be dependent upon the recipient animal strain and this may explain some of the discrepancies in function observed in different animal models when this system has been used to encapsulate pancreatic islets for a bioartificial pancreas. The tissue reaction does not seem to be affected by clinical diabetic status although abnormal immunological responses in animals with a tendency to spontaneous diabetes could be important. Attempts to reduce the reaction to the capsules in the BB/E rat strain by modifying the membrane were unsuccessful.
    Type of Medium: Electronic Resource
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