Morphological and functional changes in small-bowel allografts of pigs under combined tacrolimus and mycophenolate mofetil immunosuppression

Alessiani, M.; Spada, Marco; Costa, Antônio Gadelha da; Arbustini, Eloisa; Morbini, Patrizia; Poggi, Nicoletta; Favaro, L; Ponti, Fabrizio De; Noli, S; Dionigi, Paolo; Zonta, A.

doi:10.1016/s0041-1345(96)00417-4

Cited by 4 publications

(1 citation statement)

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“…This doubledrug regimen is currently being used in clinical intestinal and multi-visceral transplantation [24,36,371. The opportunity to have at our disposal a large, healthy, long-surviving animal model, never achieved by others [25], allowed us to carry out preliminary morphological and functional studies of the intestinal graft at a late stage after transplantation [4] and also further Large-animal models of intestinal graft rejection…”

Section: Discussionmentioning

confidence: 99%

The influence of surgery, immunosuppressive drugs, and rejection, on graft function after small bowel transplantation: a large-animal study

et al. 2003

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In this study we assessed functional changes (motility and absorption) of intestinal allografts in a large-animal model of orthotopic small bowel transplantation in swine. Studies were performed on non-rejecting animals in the early and late stages after transplantation and after induction of different grades of acute rejection. Immunosuppression consisted of oral FK506 and mycophenolate mofetil. In each study group we regulated drug administration, in terms of dosage and timing, in order to induce different grades of acute rejection or to prevent it. Migrating myoelectrical complexes were recorded in fasting animals so that motility could be assessed. Mucosal biopsy of the allograft and D-xylose absorption tests were performed on the same day as the motility study. In the early stages following intestinal transplantation, we observed in non-rejecting animals a slightly increased graft motility and a marked carbohydrate malabsorption. Recovery of the carbohydrate absorption capacity occurs within 2 months, but the persistence of diarrhea leads to partial malabsorption and to a lack of normal weight gain. Motility reduction correlates with the grade of acute rejection and becomes significant at a later stage, when rejection is severe. Allograft carbohydrate absorption, on the contrary, is markedly reduced in all rejecting pigs, irrespective of the grade of rejection. In summary, the early functional impairment of non-rejecting animals has multifactorial causes due to surgery and immunosuppression (drug toxicity), and its occurrence suggests the need for specific guidelines for clinical early postoperative enteral feeding. The functional studies adopted here are helpful in defining the grade of functional impairment with or without acute rejection; however, they are not useful for early detection of ongoing acute rejection of the small bowel graft.

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Section: Discussionmentioning

confidence: 99%

The influence of surgery, immunosuppressive drugs, and rejection, on graft function after small bowel transplantation: a large-animal study

et al. 2003

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Correlations between functional changes and different grades of acute rejection in swine small bowel allografts

Alessiani

Ponti

Ferrari

et al. 2000

Transplantation Proceedings

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Current treatment practice in immunosuppression

Ciancio

Burke

Miller

2000

Expert Opinion on Pharmacotherapy

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New drugs have recently been added that may eventually replace the two-decade dominance of cyclosporin in solid organ transplantation. This cornerstone of immunosuppression was introduced by Borel [1] and Calne [2] in the mid-70s. In 1989, Starzl et al., after 2 years of preclinical experimentation, introduced tacrolimus (originally designated as FK506 by the Fujisawa Pharmaceutical Company of Japan) as a potent immunosuppressant for liver transplants [3]. Also, in recent years, a variety of novel purine and pyrimidine biosynthesis inhibitors have been tested for transplantation therapy. The leading agent which appears to be replacing the 35-year position occupied by azathioprine is the semi-synthetic morpholinoethyl ester of mycophenolic acid (MPA), mycophenolate mofetil (MMF), introduced by Allison [4] and Sollinger [5], and developed by the Syntex Corporation (now Roche Pharmaceuticals). Others, affecting different intra- or intercellular messages amplifying immunity, are in the pipeline.

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Morphological and functional changes in small-bowel allografts of pigs under combined tacrolimus and mycophenolate mofetil immunosuppression

Cited by 4 publications

References 2 publications

The influence of surgery, immunosuppressive drugs, and rejection, on graft function after small bowel transplantation: a large-animal study

The influence of surgery, immunosuppressive drugs, and rejection, on graft function after small bowel transplantation: a large-animal study

Correlations between functional changes and different grades of acute rejection in swine small bowel allografts

Current treatment practice in immunosuppression

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