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A Tibell

Publications and source records attributed to A Tibell.

At least 73 records · Page 4Linked to original sources
PubMed1996

Improved results with a simplified technique for pancreaticoduodenal transplantation with enteric exocrine drainage.

A simplified technique for pancreaticoduodenal transplantation with enteric exocrine drainage is described. The whole-organ pancreaticoduodenal transplant is placed intraperitoneally with vascular anastomosis to the right common iliac artery and the caval vein, respectively. The graft duodenum is anastomosed side-to-side to the most proximal part of the donor jejunum. No Roux-en-Y loop or pancreatic duct catheter is used to protect the anastomosis with this technique. Nevertheless, excellent results have been obtained, with no graft losses occurring due to leakage or infection. With this technique, the 1-yr patient and graft survival rates in uremic recipients of simultaneous renal and pancreas transplants are 100% and 87%, respectively.

Anastomosis, Surgical↗
PubMed1995

Increased anti-Gal activity in diabetic patients transplanted with fetal porcine islet cell clusters.

The natural anti-Gal antibody seems to create a major obstacle for discordant xenotransplantation in humans. Anti-Gal, which is produced in large amounts in humans (1% of circulating IgG), interacts specifically with the carbohydrate structure Gal alpha 1-3Gal beta 1-4Glc-NAc-R (termed the alpha-galactosyl epitope). This epitope is present in large amounts on porcine cells, as well as on cells of other nonprimate mammals (1 x 10(6) to 35 x 10(6) epitopes/cell). The interaction of anti-Gal with alpha-galactosyl epitopes on the xenograft was found to mediate the immune destruction of discordant xenografts. In the present study, the human immune response to alpha-galactosyl epitopes on xenografts was assessed by measuring changes in anti-Gal titers and affinity in sera of diabetic patients transplanted with fetal porcine islet cell clusters. The activity of this antibody was assessed by a hemagglutination assay with RBC, by ELISA with mouse laminin as a solid-phase antigen, and by equilibrium dialysis with the radiolabeled free haptenic form of the alpha-galactosyl epitope, i.e. [3H]Gal alpha 1-3Gal beta 1-4GlcNAc. All assays revealed a marked increase in anti-Gal activity after transplantation. The increase in anti-Gal titers ranged between 8- and 64-fold. A similar increase was observed in the binding of free alpha-galactosyl epitopes to anti-Gal, as assayed in equilibrium dialysis. Immunoglobulin concentration did not increase after transplantation, suggesting that the observed increase in anti-Gal activity is the result of a specific immune response against alpha-galactosyl epitopes on the xenograft. The elevation in anti-Gal activity was observed in all three immunoglobulin classes and the highest activity was found within the IgG class. Analysis of IgG binding to fixed porcine endothelial cells suggested that most of the observed increased activity against these cells in transplanted patients may be attributed to the elevation in anti-Gal activity.

Animals↗
PubMed1995

Nutrition and allorejection impact of lipids.

Polyene n-3 and n-6 fatty acids are claimed to have immunomodulating properties. The impact of nutritional variations on transplant rejection was therefore studied in the heterotopic rat heart allotransplant model with particular focus on lipids. Twenty per cent fat emulsions with differing n-3/n-6 fatty acid ratios were continuously infused (9 g fat per kg bodyweight per day; n = 10 in each group) after transplantation until rejection: safflower oil (n-3/n-6 = 1/370), fish oil (7.6/1), soybean oil (1/6.5) and a 1:1 mixture of safflower and fish oil (1/2.1; oil control group). Graft survival time, subpopulations of infiltrating and circulating immunocompetent cells and interleukin-6 release by circulating mononuclear cells were analysed. In the safflower oil, fish oil and soybean oil groups graft survival was prolonged to 13.3, 12.3 and 10.4 days vs. 6.7 days in the oil control group and 7.8 days in the saline control group (p < 0.01). In the two groups with the highest prolongation of graft survival the number of infiltrating cells was reduced by up to 50% and the peripheral blood mononuclear cell interleukin-6 release by up to 45%. Beyond that, circulating T-cells were reduced in the fish oil group. The n-3/n-6 fatty acid ratio determines the immunomodulating effect of lipids. Both n-6 and n-3 fatty acids, if applied as the main fatty acid source, exert immunosuppressive effects by diminished infiltration, mobilization and cytokine release by immunocompetent cells. A n-3/n-6 fatty acid ratio of 1/2 proved to be immunologically neutral. The recipient's disposition to reject an allotransplant is influenced by the fatty acid composition of exogenously supplied lipids.

Animal Nutritional Physiological Phenomena↗
PubMed1995

Cyclosporin A in fat emulsion carriers: experimental studies on pharmacokinetics and tissue distribution.

In the commercially available intravenous formulation of Cyclosporin A (Sandimmun), polyoxyethylated castor oil (Cremophor EL) is used as a solubilizing agent. We have recently reported that the acute nephrotoxic effect of this preparation was alleviated by replacing Cremophor EL with a soybean oil-based fat emulsion in a rat model. To further explore the potential of fat emulsions as carriers for cyclosporin A, data on the in vivo pharmacokinetics and tissue distribution are required. In this study in pigs, the pharmacokinetics of soybean oil-cyclosporin A was compared to that of Sandimmun. The two formulations seemed bioequivalent, as there were no significant differences in the systemic clearances, volumes of distribution or elimination half-lives. Moreover, the tissue distributions of soybean oil-cyclosporin A and Sandimmun were compared in rats. These studies also included two additional lipid-based carriers: one based on iodized ester of poppy seed oil and the other on a liposomal preparation. The tissue distributions were found to be similar regardless of the carriers used. Fat emulsion carriers seem to offer possibilities for preparing better tolerated intravenous formulations of cyclosporin A while maintaining the same characteristics concerning pharmacokinetics and tissue distribution.

Animals↗
PubMed1995

[Immunosuppressive effect of parenteral fat emulsions in defined immunostimulation].

BACKGROUND: In the heterotopic rat heart allotransplant model we have previously shown that intravenous fat emulsions are to a various extent immunosuppressive or immunoneutral, dependent on their n-3/n-6 fatty acid ratio. Safflower oil (n-3: n-6 = 1:370), fish oil (7.6:1) and soybean oil (1:6.5) prolonged the transplant survival time to 13.3, 12.3 and 10.4 days compared to 6.7 days (oil control group; 1.2.1) and 7.8 days (saline control group) (p < 0.01), respectively. This study presents a correlation of graft survival to immunohistological, cell biological and biochemical parameters. MATERIALS AND METHODS: 20% emulsions of safflower oil, fish oil, soybean oil and a 1:1 mixture of safflower and fish oil (oil control group) were continuously infused (9 g fat/kg body weight/day; n = 10 each group) after transplantation. Subpopulations of infiltrating and circulating immunocompetent cells and leukotriene B4 and B5 release of circulating mononuclear cells were analyzed (on the 4th postoperative day). RESULTS: In the 2 groups with the highest prolongation of graft survival the number of infiltrating cells was reduced by up to 40% and the peripheral blood mononuclear cell interleukin-6 release by up to 45%. Beyond that, circulating T cells were reduced in the fish oil group. Leukotriene B4 was released in all groups to the same extent, leukotriene B5 exclusively in the fish oil group. CONCLUSIONS: Intravenous fat emulsions show a varying immunomodulatory effect in dependence of the n-3/n-6 fatty acid ratio. Both n-6 and n-3 fatty acids, if applied as main fatty acid source, exert immunosuppressive effects by a diminished infiltration and mobilisation of immunocompetent cells. Soybean oil with a more balanced n-3/n-6 fatty acid ratio than safflower oil is significantly less immunosuppressive than safflower oil, and fat emulsions with a n-3/n-6 fatty acid ratio of 1:2 are immunologically neutral.

Animals↗
PubMed1994

Transplantation of porcine fetal pancreas to diabetic patients.

Transplantation of fetal porcine islet-like cell clusters (ICC) reverses diabetes in experimental animals. We have now transplanted porcine ICC to ten insulin-dependent diabetic kidney-transplant patients. All patients received standard immunosuppression and, at ICC transplantation, antithymocyte globulin or 15-deoxyspergualin. ICC were injected intraportally or placed under the kidney capsule of the renal graft. Four patients excreted small amounts of porcine C-peptide in urine for 200-400 days. In one renal-graft biopsy specimen, morphologically intact epithelial cells stained positively for insulin and glucagon in the subcapsular space. We conclude that porcine pancreatic endocrine tissue can survive in the human body.

Adult↗
PubMed1994

Lipid mediated modification of rat heart allograft survival.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Cyclosporin A in fat emulsion carriers: studies on the immunosuppressive potential, using the heterotopic heart transplant model in rats.

Cyclosporin A (CyA) is an extremely lipophilic drug that needs a solubilizing agent to become soluble in water. In the commercially available intravenous formulation--Sandimmun--Cremophor EL is used for this purpose. It is likely that Cremophor EL contributes to some of the side effects produced by i.v. Sandimmun. We have recently shown that if Cremophor EL is replaced by a soybean oil (SBO)-based fat emulsion carrier, the acute renal side effects following i.v. administration of CyA are avoided in a rat model. It is then important to ascertain whether the use of a fat emulsion carrier alters the immunosuppressive effect of CyA. Moreover, fatty acids can themselves influence the immune system, and both omega-3 and omega-6 fatty acids have been reported to possess immunosuppressive properties. In the present study, the effect on graft survival of i.v. CyA administered in five different formulations, using fat emulsions or liposomes as carriers, was compared to that of conventional Sandimmun infusion substance in the heterotopic heart transplant model in rats. The new formulations tested did not reduce the immunosuppressive effect of CyA. On the contrary, a small but significant increase in graft survival was noted in the groups given CyA in the SBO-based fat emulsion carrier (17.0 +/- 0.82 days) and CyA in liposomes (16.0 +/- 0.63 days) as compared to the results in the Sandimmun-treated group (15.0 +/- 0.58 days: P < 0.01 and P < 0.05, respectively).

Animals↗