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  • 1
    ISSN: 1432-2277
    Keywords: Lipid emulsion, rat, heart ; Heart, rat, lipid emulsion ; Immunosuppression, lipid emulsion, rat, heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect on allograft survival of intravenous fat emulsions that differed in the ratio of functionally important n-3 and n-6 fatty acids was studied in a heterotopic cardiac transplant model in rats. Twenty percent fat emulsions were administered by continuous infusion at a dosage of 9 g fat/kg body weight per day, starting immediately after transplantation and continuing until complete rejection. The n-6 and n-3 fatty acids represent 75%, 43%, 60%, and 59% of all fatty acids in safflower oil, fish oil, soybean oil, and a 1:1 mixture of safflower and fish oil, respectively. The n-6 fatty acids predominate in safflower oil (370/1) and soybean oil (6.5/1), while the n-3 fatty acids dominate in the fish oil (7.6/1). The 1:1 mixture of safflower and fish oil has the balanced composition (n-6/n-3=2.1/1) recommended by Kinsella and served as oil-treated controls. Continuous infusion of safflower oil, fish oil, and soybean oil prolonged graft survival time to 13.3, 12.3, and 10.4 days, respectively, compared to 6.8 days in the oil-treated controls (P〈0.01 for all comparisons). Another control group infused with saline rejected the allografts after 7.8 days (P=NS compared to oil-treated controls; P〈0.01 for all other comparisons). The data suggest that intravenous administration of polyunsaturated fat emulsions results in an immunosuppressive effect that seems to be dependent on the n-3/n-6 fatty acid ratio of the fat emulsion. The n-6 fatty acids turned out to be just as immunosuppressive as the n-3 fatty acids if each fatty acid family was applied as the main polyunsaturated fatty acid source. Soybean oil with a n-3/n-6 fatty acid ratio, coming closer to the ratio of the oil-treated controls, was significantly less immunosuppressive than safflower oil.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2277
    Keywords: Key words Xenotransplantation ; 15-deoxyspergualin ; Guinea pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study aimed to investigate the effects of 15-deoxyspergualin (DSG), tacrolimus (FK 506) and cyclosporin A (CyA), alone or in combination, on delayed xenograft rejection (DXR). We used the guinea-pig-to-C6-deficient (C6–)-PVG-rat heart transplantation model, since in this strain combination, hyperacute rejection is avoided. In C6- control rats, the guinea pig xenografts survived for 39.2 ± 6.3 h (mean ± SD). Splenectomy alone resulted in a xenograft survival of 71.8 ± 7.8 h, but the addition of CyA or FK 506 did not further improve graft survival (73.6 ± 3.0 h and 72.0 ± 17.6 h, respectively). In contrast, DSG treatment increased graft survival to a mean of 99.8 ± 9.2 h. When CyA or FK 506 was combined with DSG, no additional effects were observed (105 ± 24.3 h and 95.1 ± 5.6 h, respectively). DSG alone or in combination with FK 506 or CyA resulted in a significant reduction in the serum IgM levels and reduced the deposits of IgM and IgG in rejected grafts. However, all xenografts were still heavily infiltrated by ED1 + macrophages, regardless of the treatment used. Thus, DSG treatment resulted in moderate prolongation of xenograft survival in C6– rats. The effect seems to be related to suppression of xenoreactive antibody production. To prolong xenograft survival further, strategies that inhibit macrophage infiltration seem required.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1436-0691
    Keywords: Key words Clinical xenoislet transplantation ; Xenoanti-bodies ; Porcine endogenous retrovirus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 1990–1993, eight diabetic renal transplant patients had porcine fetal islets injected intraportally at Huddinge Hospital in Stockholm. Four of the patients had evidence of xenograft function reflected in the excretion of small amounts of porcine C-peptide. Two patients had the porcine fetal islets placed under the capsule of a simultaneously transplanted kidney. In one of these patients, a graft biopsy specimen taken 3 weeks after transplantation revealed morphologically intact epithelial cells staining positively for insulin and glucagon. The insulin production was in all instances insufficient to affect the patient's insulin requirements. All patients formed specific xenoantibodies (mostly anti-Gal); presumably, most of the xenoislets were destroyed by rejection. On follow-up studies carried out 6–8 years after xenotransplantation, most patients still had higher-than-pretransplant levels of xenoantibodies. There was no evidence of transmission of porcine endogeneous retroviruses to the patients. All patients expressed a positive attitude toward the use of animal tissue for treatment of disease, and none of the patients regretted participating in the trial. Cell transplantation is leading the way at present for clinical xenotransplantation. The finding that complement inhibition protects intraportally injected porcine islets from an injurious incompatibility reaction holds promise for future clinical application. A similar protective effect might be achievable with the use of islets from transgenic pigs expressing human complement receptors.
    Type of Medium: Electronic Resource
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