| 1. |
- Tufveson, G, et al.
(författare)
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Hyaluronic acid accumulation; the mechanism behind graft rejection edema.
- 1992
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Ingår i: Transplant International. - 0934-0874 .- 1432-2277. ; 5 Suppl 1, s. S688-9
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Tidskriftsartikel (refereegranskat)abstract
- Hyaluronic acid (HA) is an important stabilizing consistuent of the loose connective tissue and regulates water homeostasis. Thus, excessive accumulation of HA in interstitial tissue immobilizes water and may thereby contribute to interstitial tissue edema. By the use of biotin labelled core protein and an avidin-enzyme system, we visualized HA in grafted rat kidney, rat heart, rat small bowel and also in human kidneys. By an extraction procedure the tissue amounts of HA were measured in the experimental grafts. Simple techniques for measuring water content were also employed. The extracellular amounts of HA increased between 100% and 350% in rejecting tissues as compared to syngeneic controls. The relative water content also increased and correlated well with the HA accumulation. The clinical value of these experimental observations was confirmed in human transplantation where rejecting kidney allografts demonstrated a highly significant increase in HA staining in the interstitium as compared to non-rejecting biopsy specimens. We therefore concluded that transplantation edema--a key features of graft rejection--is regulated by the accumulation of HA not only under experimental conditions but also in the clinical setting.
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| 2. |
- Wallander, J, et al.
(författare)
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Intestinal distribution of hyaluronan in small bowel allografting in the rat.
- 1993
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Ingår i: Transplant International. - 0934-0874 .- 1432-2277. ; 6:3, s. 133-7
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Tidskriftsartikel (refereegranskat)abstract
- Hyaluronan (hyaluronic acid; HA) was demonstrated and quantified in small bowel tissue at different times after small bowel transplantation. Semiallogeneic or semisyngeneic rat models were used to elicit either unidirectional graft rejection or graft-versus-host disease (GVHD). In normal rat small bowel, HA was present in the villous lamina propria and around medium-sized vessels in the interstitium of the crypt area. During graft rejection a cellular infiltrate and edema appeared in the lamina propria in the crypt area where an accumulation of HA was also demonstrated. There was progressive accumulation of HA in the small bowel during rejection, and on day 6 there was a threefold increase compared to the values in syngeneic grafts. The increase in tissue HA was paralleled by an increase in the total water content of the rejecting graft. In specimens from animals suffering from GVHD, no significant changes in water or HA content and distribution were observed until day 12. The data suggest that accumulation of HA might contribute to the pathophysiology of the transplantation edema and that HA might be of potential diagnostic value in differentiating between graft rejection and GVHD.
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| 3. |
- Wanders, A., et al.
(författare)
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Effect of LS-2616 on the graft protection achieved by cyclosporin A, prednisolone, and 15-deoxyspergualin in heart-transplanted rats
- 1992
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Ingår i: Transpl Int. ; 5 Suppl 1, s. S462-3
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Tidskriftsartikel (refereegranskat)abstract
- The immunostimulator LS-2616 abolishes the effect of cyclosporin A in a rat cardiac transplantation model. The present paper compares the characteristics of rejection obtained under different immunosuppressive regimens with and without additional LS-2616 application in the same model. Cyclosporin A (CyA, 10 mg/kg daily), prednisolone (15 mg/kg daily), or 15-deoxyspergualin (2, 5, or 10 mg/kg daily), all given from the day of transplantation until day 9, protected the grafts during the treatment period. The addition of LS-2616 (160 mg/kg, day -1 until stop) resulted in a total abrogation of the immunosuppressive effect of CyA and prednisolone. However, LS-2616 could only partially or not at all reverse the effect of 15-deoxyspergualine. These results show a certain drug selectivity of LS-2616 in promoting rejection of immunosuppressed allografts. Further studies with LS-2616 may be of benefit in evaluating the mode of action of different immunosuppressive compounds and, thus, contribute to finding more effective antirejection therapies.
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| 4. |
- Wanders, A., et al.
(författare)
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Enhancement of the effect of low-dose cyclosporin A by sulphasalazine in prevention of cardiac allograft rejection in the rat
- 1992
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Ingår i: Transpl Int. ; 5:3, s. 155-8
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Tidskriftsartikel (refereegranskat)abstract
- Sulphasalazine (SASP) is an immunomodulatory compound with disease-modifying activity in ulcerative colitis and in other autoimmune disorders. SASP was previously shown to prolong the survival of heart allografts in rats treated with cyclosporin A (CyA) for 9 days after transplantation. We have now evaluated whether SASP also exerts a beneficial effect under continuous treatment with CyA, when CyA is discontinued after 14 days, or alone if given 10 days prior to transplantation. Cardiac grafts were transplanted from PVG donors to Wistar/Kyoto recipients using an accessory cervical heart transplantation technique. Rejection was defined as the absence of palpable contractions and occurred in the control group in a very reproducible manner on day 8 or 9. SASP alone was given orally (100 mg/kg body weight) starting 10 days before transplantation and resulted in a minor prolongation of graft survival. When SASP was given in addition to oral CyA (1 mg/kg or 2 mg/kg from day 0 to rejection) there was a significant prolongation in graft survival [from medians of 8 (range 6-11) and 9 (range 8-11) days, respectively, to medians of 10 (range 8-15) and 12 (range 11-15) days, respectively]. When SASP was given from day 0 to rejection, in addition to a schedule of oral CyA (10 mg/kg) for 15 days, there was no prolongation of graft survival [median of 30 (range 26-42) days vs median of 32 (26-38) days]. The data show that SASP acts as a weak immunosuppressive agent which enhances the effect of CyA given at a low dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 5. |
- Friman, Styrbjörn, 1948, et al.
(författare)
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Adjuvant treatment with ursodeoxycholic acid reduces acute rejection after liver transplantation.
- 1992
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874. ; 5 Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- Acute rejection, occurring with a reported frequency of 50-70%, is still a dominating problem after liver transplantation. Medication with ursodeoxycholic acid (UDCA) has beneficial effects in different cholestatic conditions and has also been shown to reduce HLA class I antigen expression on hepatocytes in patients with PBC. Since August 1989 we have consecutively treated all patients with primary graft function with UDCA (n = 41). Patients transplanted in the first half of 1989 served as a control group (n = 8). All patients in this study were given sequential quadruple drug immunosuppression. The treatment group were given oral UDCA 10 mg/kg per day. During the first postoperative month, 17% of the UDCA-treated patients had an episode of acute rejection compared with 75% of the control patients (P < 0.01). Liver biochemistry tests 1 month postoperatively were significantly better in patients treated with UDCA. The results suggest that adjuvant treatment with UDCA reduces acute liver graft rejection.
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| 6. |
- Friman, Styrbjörn, 1948, et al.
(författare)
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The bile acid independent flow is reduced in the transplanted liver.
- 1992
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874. ; 5 Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- Bile secretion is an important indicator of liver graft function. Reports on bile formation by the transplanted liver with stable function some months after operation are scarce. In this study bile flow, bile salt secretion rate (BSSR) and biliary clearance of polyethylene glycol (PEG) 900, a marker of canalicular bile flow, were studied in a group of liver-transplanted (LTX) patients (n = 8) 3-6 months after transplantation. A group of cholecystectomized patients with indwelling T-tubes (n = 6) served as a control group. Both groups were treated with oral ursodeoxycholic acid (500 mg/day). On the day of the study bile was drained for 6 h by gravity and four-hourly samples were used in the calculations. The relation between bile flow and BSSR analysed with linear regression showed a reduced bile acid independent flow in the liver-transplanted group (0.11 ml/min) compared with the control group (0.20 ml/min). The relation between biliary clearance of PEG 900 and BSSR showed a significantly steeper slope for the cholecystectomized control patients (1.40 ml/micromol) compared with the liver-transplanted patients (0.30 ml/micromol). We conclude, that in spite of stable graft function with normal liver enzmyes, the transplanted liver has a reduced bile acid independent bile flow. The transplanted liver also has a reduced biliary clearance of PEG 900 indicating a reduced canalicular bile flow. The cause of this impaired bile formation could be due to the influence of the immunosuppressive drug cyclosporin, the result of damage to the liver during preservation and reperfusion or the continuous immunological challenge to the graft.
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| 7. |
- Olausson, Michael, 1956, et al.
(författare)
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Adjuvant treatment with ursodeoxycholic acid prevents acute rejection in rats receiving heart allografts.
- 1992
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874. ; 5 Suppl 1
-
Tidskriftsartikel (refereegranskat)abstract
- Adjuvant treatment with ursodeoxycholic acid (UDCA) for liver-transplant recipients has been reported to reduce the frequency of acute rejection episodes. To explore this effect further, UDCA was given to rats in an experimental heart transplantation model, with or without concomitant immunosuppressive treatment with antihymocyte globulin (ATG). UDCA was administered orally 7 days before and 14 days after transplantation. Rats treated with UDCA alone or in combination with ATG were compared with untreated controls and ATG-treated recipients. Adjuvant treatment with UDCA was found to induce prolonged graft survival and increase the amount of transplant tolerance in rats. Serum levels of bilirubin and aminotransferases were not altered irrespective of the UDCA dose given. The results indicate that UDCA has an immunomodulatory capacity that might not be restricted to the liver, but also might apply to other transplanted organs as well.
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| 8. |
- Persson, Hans, 1948, et al.
(författare)
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Glomerular filtration rate after liver transplantation with a low-dose cyclosporin protocol.
- 1994
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874. ; 7:3, s. 172-6
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Tidskriftsartikel (refereegranskat)abstract
- Cyclosporin nephrotoxicity is a well-known complication in organ transplantation. In successful liver transplantation, a moderate degree of renal impairment is accepted. Whether this impairment is continuously progressive, stabilizes with time, or is reversible is not known. We have prospectively evaluated the glomerular filtration rate (GFR) using 51CrEDTA plasma clearance in 29 liver transplant patients (11 males and 18 females) with a mean age of 49 years (range 22-62 years). The 51CrEDTA plasma clearance measurements were performed preoperatively and at 3, 6, 12, 24, and 36 months after the liver transplantation. All but six patients were given sequential, quadruple drug therapy with antithymocyte globulin, azathioprine, steroids, and cyclosporin. Intravenous cyclosporin was avoided and oral cyclosporin started when renal function was stable. Cyclosporin was started in a dose of 8 mg/kg body weight, aiming at whole blood through levels (specific monoclonal technique) of 200 micrograms/l in the postoperative period; thereafter, the dosage was rapidly tapered down, aiming at whole blood trough levels of less than 100 micrograms/l at 3 months (1.5-2 mg/kg body weight). From a mean preoperative GFR of 89 +/- 3 ml/min per 1.73 m2, all patients declined in renal function after transplantation to a mean of 64 +/- 4 ml/min per 1.73 m2 3 months after transplantation, and starting in the 3rd month the renal function was stable at about 70% of the preoperative value. No correlations were found between cyclosporin peak level or accumulated cyclosporin dose and renal impairment. We conclude that liver transplantation with cyclosporin immunosuppression will induce renal impairment even if cyclosporin blood levels are carefully monitored and kept low.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 9. |
- Svensson, G, et al.
(författare)
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Quantitative measurements of collateral arterial blood flow in nonarterialized rat liver grafts.
- 1994
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874. ; 7:2, s. 136-9
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Tidskriftsartikel (refereegranskat)abstract
- The early development of arterial blood flow in the grafted liver after orthotopic liver transplantation in the rat without reconstruction of the hepatic artery was studied. Arterial liver blood flow was measured on day 21 after transplantation with NEN-TRAC microspheres (size 15.5 +/- 0.1 microns) and labelled with 103Ru. The arterial liver blood flow in the grafted liver was 0.778 +/- 0.247 ml/min per gram for transplanted rats after 21 days. One day after transplantation, the blood flow was only 0.006 +/- 0.002 ml/min per gram. The results of this study demonstrate that there was no arterial blood flow on day 1 after transplantation, as expected, but that there was a high arterial blood flow in the transplanted liver by day 21. This was also supported by the angiographic findings. The early development of arterial blood flow via collaterals may account for the excellent results that we and others have attained in orthotopic liver transplantation without rearterialization in the rat.
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| 10. |
- Thune, Anders, et al.
(författare)
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Raised pressure in the bile ducts after orthotopic liver transplantation.
- 1994
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874. ; 7:4, s. 243-6
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Tidskriftsartikel (refereegranskat)abstract
- Biliary complications are common after orthotopic liver transplantation. Bile leakage in the immediate postoperative period and on removal of the T-tube could possibly be caused by a raised bile duct pressure. In order to test this hypothesis, bile duct pressure was studied in seven consecutive liver transplant patients. During the operation, the common bile duct was anastomosed end-to-end over a T-tube. The initial bile duct pressure measurement was performed a median of 12 days (range 10-17 days) after the transplantation and on one or two more occasions during the following 3 months. Seven cholecystectomized gallstone patients with indwelling T-tubes were used as controls. The bile duct pressure at the level of the xiphoid process in the transplanted group was 7.7 +/- 1.4 cm H2O and in the control group 0.5 +/- 0.8 cm H2O (P < 0.001). The initially increased bile duct pressure after liver transplantation decreased with time (P < 0.05) towards normal during the following 3 months. The raised pressure may increase the risk of bile leakage in the postoperative period.
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