Biomedical subjects

A Tibell

Publications and source records attributed to A Tibell.

129 records · Page 8Linked to original sources

PubMedDate not supplied

Immunoregulation by parenteral lipids: impact of the n-3 to n-6 fatty acid ratio.

BACKGROUND: The immune system is reported to be influenced by polyunsaturated fatty acids. Therefore, immunoregulation caused by intravenous fat emulsions with different n-3 to n-6 fatty acid ratios was studied in an in vivo model. METHODS: Experimental rat heart allotransplantation served as a defined immunologic challenge. Twenty percent emulsions of safflower oil (n-3 to n-6 = 1:370), fish oil (n-3 to n-6 = 7.6:1), and soybean oil (n-3 to n-6 = 1:6.5), and a 1:1 mixture of safflower oil and fish oil (n-3 to n-6 = 1:2.1) were continuously infused (9 g of fat per kg of body weight per day) after transplantation until complete rejection. The prolongation of graft survival, an accepted parameter of immunosuppression, was assessed. Beyond that, cytokine release by mitogen-stimulated peripheral-blood mononuclear cells (PBMCs) from animals exsanguinated on day 4 after transplantation was evaluated. RESULTS: The mean rejection time was 7.8 days in the sham-infused saline control group and 6.7 days in the safflower- and fish-oil-mixture group (oil control group). Continuous infusion of soybean oil prolonged the graft survival time to 10.4 days, fish oil to 12.3 days, and safflower oil to 13.3 days. PBMC alpha-tumor necrosis factor release was significantly reduced in the fish-oil group (51.9 +/- 13.0 pg/10(6) PBMCs vs 70.8 +/- 10.9 pg/10(6) PBMCs [controls], p < .004). Interleukin-6 release was diminished in both the fish-oil group (22.2 +/- 13.6 pg/10(6) PBMCs vs 40.7 +/- 8.3 pg/10(6) PBMCs [controls], p < .002) and the safflower-oil group (28.4 +/- 6.9 pg/10(6) PBMCs, p < .002). CONCLUSIONS: The n-3 to n-6 fatty acid ratio determined the immunoregulatory potential of intravenous fat emulsions in vivo. Both n-3 and n-6 fatty acids were immunosuppressive when applied as the main polyunsaturated fatty acid sources. PBMC cytokine release was significantly reduced in these groups. The more balanced the n-3 to n-6 ratios, the less immunosuppressive the fat emulsion. There was no immunosuppressive effect at an n-3 to n-6 ratio of 1:2.1.

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PubMedDate not supplied

Longitudinal studies on the microcirculation around the TheraCyte immunoisolation device, using the laser Doppler technique.

Encapsulation of cellular grafts in an immunoisolation membrane device may make it possible to perform transplantation without having to give immunosuppressive drugs. A common problem is the development of an avascular fibrotic zone around the implants, leading to impaired graft survival. The TheraCyte macroencapsulation device has therefore been designed to facilitate neovascularization of the device's surface. In this study, we evaluated the microcirculation around empty TheraCyte devices implanted SC in rats at various times after implantation, using a laser Doppler probe introduced via the device port. Studies were performed on day 1 or at 1, 2, and 4 weeks or at 2, 3, and 12 months after implantation. The mean flow was 158+/-42, 148+/-50, 133+/-28, 72+/-17, 138+/-41, 165+/-43, and 160+/-29 perfusion units (PU), respectively. Thus, the microcirculation around the device was significantly reduced at 4 weeks after implantation (p < 0.01) while, from 2 months onwards the circulation had improved and did not differ significantly from that on day 1. The present study shows time-related changes in the microcirculatory flow around TheraCyte macroencapsulation devices that agree with our previous microdialysis studies on in vivo exchange of insulin and glucose between the device and the circulation. Laser Doppler flowmetry seems to provide a reliable technique for screening blood perfusion around macroencapsulation devices.

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PubMedDate not supplied

In vivo evaluation of glucose permeability of an immunoisolation device intended for islet transplantation: a novel application of the microdialysis technique.

Immunoisolation devices consist of semipermeable membranes chosen to protect the islets from the immune system but still allow sufficient passage of nutrients, oxygen, and the therapeutic products, insulin. The exchange between the device and the microcirculation will influence the survival of the graft as well as the metabolic efficacy of the islet implant. Glucose is the important trigger factor for insulin secretion. In this study, we evaluate the in vivo glucose permeability of the Theracyte immunoisolation device at various times after implantation. Empty devices were implanted s.c. in rats. The glucose kinetics in the device was compared to that in the SC tissue during i.v. glucose tolerance tests (IVGTTs), using the microdialysis technique. In rats studied on day 1, or 1, 2, and 4 weeks after implantation, the peak glucose levels (Cmax) were significantly lower, the times-to-peak (TTP) were significantly longer, and the areas under the curve during the first 40 min (AUC(0-40)) were significantly smaller in the device than in the SC fat. However, at 3 months all parameters improved and Cmax, TTP, and AUC(0-40) in the device did not differ significantly from those measured in the SC fat. Thus, during the first 4 weeks the device constitutes a significant diffusion barrier, but at 3 months the exchange between the lumen of devices and the blood stream improves. Our data indicate that implantation of the device several months before transplantation of the cellular graft would improve the exchange across the membrane during the early posttransplant period. This should have positive effects on graft survival and function. We also suggest that microdialysis is a useful tool for evaluating the in vivo performance of macroencapsulation devices.

Animals↗