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Z Gaciong

Publications and source records attributed to Z Gaciong.

At least 19 recordsLinked to original sources
PubMed2001

Fucoidan improves the renal blood flow in the early stage of renal ischemia/reperfusion injury in the rat.

It has been shown that monoclonal anti-P-selectin antibody administration protects renal function in an ischemic model of acute renal failure. This study was designed to evaluate the effect of administration of fucoidan, P-selectin inhibitor, on reduction in renal blood flow induced by ischemia/reperfusion injury in the rat. Experiments were performed on male Wistar rats weighting 35-400 g. The systemic blood pressure (mm Hg) (BP) and renal blood flow (RBF) were monitored continuously and renal vascular resistance (RVR) was calculated. After 20 min period of stabilization animals (6 rats in each group) received one of the following agents administered by continuous i.v. infusion during 165 min: 1 mg/kg of body weight of fucoidan (F1), 10 mg/kg of fucoidan (F10), 100 mg/kg of fucoidan (F100), 10 mg/kg of heparin (H), or 0.9% NaCl solution (control). After 15 min of drug administration the renal vessels of the both kidney were occluded with vascular clamps for 60 min. There were no significant changes in the initial values of RBF, RVR and BP between groups. None procedure affected significantly BP during all experiments. In F10 RBF returned to the initial values in 70th min of reperfusion and did not change up to 90th min. This value was significantly higher than respective value in the control group. In F1 group RBF in 90th min was also higher than in the control group, but it was not statistically significant. The dose of heparine and fucoidan used in the H and F100 groups failed to preserve RBF during reperfusion. In the present study we found that administration of fucoidan--P-selectin inhibitor, increases significantly postischemic renal blood flow and may have renoprotective activity.

Animals↗
PubMed2000

Arteriosclerosis in rat aortic allografts: early changes in endothelial integrity and smooth muscle phenotype.

BACKGROUND: Transplant arteriosclerosis remains a limiting factor for the long-term survival of transplanted organs and effective treatment is lacking. A rat model of aortic allografts was used to analyze this process by electron microscopy and further characterize the phenotypic properties of the cells involved. METHODS: A segment of abdominal aorta was transplanted orthotopically from Fischer to Lewis rats. The animals were killed 1-12 weeks after the operation (four to six rats/group), and the grafts were removed and processed for microscopy. RESULTS: The first changes (1 week) included detachment of endothelial cells, adhesion of degranulating platelets to the subendothelial matrix, and modification of smooth muscle cells in the media. The latter process was distinguished by loss of myofilaments and formation of a prominent endoplasmic reticulum and Golgi complex (shift from contractile to synthetic phenotype). Subsequently, modified smooth muscle cells invaded the intima. In parallel, lymphocytes and monocytes/macrophages infiltrated the intima and adventitia. The neointima grew in size by cell proliferation and production of extracellular matrix (4-8 weeks). Smooth muscle cells and monocytes/macrophages in the neointima and media were also noted to accumulate cytoplasmic lipid droplets and eventually turn into foam cells and die. Within the lipid-rich cell remnants, calcification occurred. Finally (12 weeks), the growth in mass of the intimal lesions ceased and in some places reformation of an endothelial lining was detected. Few viable smooth muscle cells remained in the media and the inflammatory infiltrate in the adventitia was reduced. CONCLUSIONS: These observations highlight the importance of early changes in endothelial integrity and smooth muscle phenotype in the development of allograft vascular disease and form the basis for a partly modified model of the cellular mechanisms in this process.

Animals↗
PubMed2000

Donor DNA can be detected in recipient tissues during rejection of allograft.

The main source of donor DNA in recipients of allograft are "passenger" cells. It is claimed that they are responsible for the posttransplantation microchimerism and prolongation of allograft survival. We have observed that besides cellular microchimerism, donor DNA can be found in the recipient tissues at the time of rejection of the allograft. In this study, we provide evidence for the presence in the recipient of both DNA in "passenger cells" and free DNA in tissues at the terminal stage of rejection. Male BN (RT1 n) rat heart or skin was transplanted to female LEW (RT1 l) rats followed by a vascularized bone marrow in a hindlimb transplant. In another group, heart and skin were transplanted followed by immediate i.v. infusion of donor-type bone marrow cells. CsA was given in a dose of 17 mg/kg body weight for 30 days, then the rats were followed up until day 100 unless rejection occurred earlier. LEW blood, spleen, mesenteric node and bone marrow cells were stained with moAb OX27 specific for BN but not LEW. Genomic male DNA was isolated and amplified with SRY oligonucleotide. At day 30 and day 100 cellular microchimerism was detected in blood, spleen, nodes and bone marrow cells. Donor DNA was detected in recipient skin, liver and heart extracts, as well as lymphoid organs, at the time of rejection of allograft, but not when the rats were maintained on CsA. Taken together, donor DNAwas detected in recipient tissues at the time of heart or skin rejection. It appeared to be released from cells of rejecting grafts and not from "passenger" cells, representing only a minor cellular mass compared with the graft.

Animals↗
PubMed2000

Fucoidan inhibits smooth muscle cell proliferation and reduces mitogen-activated protein kinase activity.

OBJECTIVES AND DESIGN: fucoidan has previously been shown to inhibit the proliferation of arterial smooth muscle cells both in animal models and in vitro. However, the mechanisms behind the anti-proliferative effects of this polysulfated polysaccharide are not known in detail. Here, the inhibitory effect of fucoidan on rat aortic smooth muscle cell proliferation was examined and compared with the effects of heparin after stimulation with fetal calf serum, platelet-derived growth factor BB, basic fibroblast growth factor, heparin-binding epidermal growth factor, and angiotensin II. MATERIALS AND METHODS: the cultures were analysed with respect to cell proliferation and DNA synthesis by cell counting and measurement of(3)H-thymidine incorporation. Phosphorylation of mitogen-activated protein kinase and nuclear translocation of phosphorylated mitogen-activated protein kinase were studied by immunoblotting and immunocytochemistry. RESULTS: fucoidan was shown to be a more potent inhibitor of smooth muscle cell proliferation than heparin. Fucoidan also reduced growth factor-induced activation of mitogen-activated protein kinase and prevented nuclear translocation of phosphorylated mitogen-activated protein kinase. CONCLUSION: fucoidan is a more potent anti-proliferative polysulphated polysaccharide than heparin and may mediate its effects through inhibition of the mitogen-activated protein kinase pathway in a similar manner as heparin.

Angiotensin II↗
PubMed1999

Factors affecting reactivation of Epstein-Barr virus infection after kidney allograft transplantation.

OBJECTIVES: Reactivation of Epstein-Barr virus (EBV) infection in renal transplant recipients may cause significant morbidity and mortality. To evaluate factors associated with activation of EBV replication we followed prospectively a group of 65 recipients of cadaveric kidney for 12 months. METHODS: Sera were collected periodically from these patients and analyzed for the presence of specific anti-EBV antibodies. Control group consisted of renal (n=35) and healthy blood donors (n=35). Enzyme-linked immunoassays based on recombinant EBV proteins were used to detect the following antibody specificities: early antigen (EA) IgA, IgM, and IgG, nuclear antigen (EBNA) IgG. RESULTS: During first year after transplantation, primary infection developed in 4 (6.15%) recipients and reactivation occurred in 18 (27.7%) recipients. Analysis did not show the association of reactivation with type of basic immunosuppressive therapy, prophylactic or therapeutic use of anti-lymphocyte antibodies, as well as acute rejection episodes. There was a borderline association (p=0.068) between the incidence of CMV infection and EBV reactivation. CONCLUSIONS: Our data suggest casual relationship between CMV infection and EBV reactivation.

Adult↗
PubMed1999

DNA from rejecting allografts can be detected in recipient nonlymphoid tissues.

The main source of donor DNA in recipients of allograft are "passenger" cells. They are claimed to be responsible for the posttransplantation microchimerism and prolongation of allograft survival. We have noticed that beside of the cellular microchimerism, donor DNA can be found in the recipient tissues at the time of rejection of allograft. In this study we provide evidence for presence in the recipient of both, DNA in "passenger cells" and free DNA in tissues at terminal stage of rejection. Male BN (RTIn) rat heart or skin were transplanted to female LEW (RTII) rats followed by a vascularized bone marrow in hind-limb transplant. CsA was given in a dose of 17mg/kg b.w. for 30 days, then rats were followed until day 100 unless rejection occurred earlier. LEW blood, spleen, mesenteric node and bone marrow cells were stained with moAb OX27 specific for BN but not LEW. Genomic male DNA was isolated and amplified with SRY oligonucleotide. At day 30 and 100 cellular microchimerism was detected in blood, spleen, nodes and bone marrow cells. Donor DNA was detected in recipient skin, liver and heart extracts, beside of lymphoid organs, at the time of rejection of allograft but not when rats were maintained on CsA. Taken together, donor DNA can be detected in recipient tissues at the time of heart or skin rejection. It seems to be released from cells of rejecting grafts and not from "passenger" cells representing only a minor cellular mass compared with the graft.

Animals↗
PubMed1998

Cyclosporine A blood concentration during pregnancy in renal allograft recipients.

Pregnancy-induced changes increase hazards associated with cyclosporine (CsA) treatment. Blood CsA trough levels (C0) were estimated in 15 pregnant renal allograft recipients treated with prednisolone + CsA + azathioprine using the TDx Abbott fluorescent polarization immunoassay. Despite therapeutical dose levels of CsA administered during pregnancy (3.52-3.67 and 3.59 mg/kg body weight in the first, second, and third trimesters, respectively), C0 significantly decreased (first trimester 130.8 +/- 36.9, second 92.0 +/- 32.7, and third 99.0 +/- 36.9 ng/ml). The mean increase of patient's body weight in mid-pregnancy was 3.0 +/- 2.19 kg and was associated with a significant (P < 0.05) fall in a hematocrit value (from 42 +/- 4.9% prior to pregnancy to 34 +/- 6% at the 20th week). We postulate that C0 concentration does not reflect the true exposure to CsA as no episodes of acute graft rejection were observed during pregnancy.

Adult↗
PubMed1998

Long-term results of treatment of chronic hepatitis B, C and D with interferon-alpha in renal allograft recipients.

The aim of this study was to evaluate the efficacy and safety of interferon-alpha (IFN-alpha) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN-alpha three times weekly for 6 months. After IFN-alpha therapy, 18 patients (43%) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN-alpha therapy. Repeated liver biopsy was performed in 16 patients after 6-24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN-alpha therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN-alpha therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long-term follow-up (median 22 months, range 0-84 months). IFN-alpha seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.

Adult↗
PubMed1998

Tolerance induction following allogeneic vascularized bone marrow transplantation--the possible role of microchimerism.

We have noticed that bone marrow transplanted in a vascularized limb graft, providing a continuous supply of donor bone marrow cells (BMC), may prolong the survival time of a skin graft from the same donor. The question arises whether the microchimerism raised plays a role in the prolonged survival of skin allografts. The aim of the study was to follow the development of microchimerism after allogeneic vascularized bone marrow transplantation (VBMTx) concomitantly with the rejection process of transplanted skin. Brown Norway (BN) rats served as donors and Lewis rats as recipients of VBMTx and free skin flap allografts. A hind limb was transplanted, followed by a full-thickness skin graft on the dorsum. Cellular microchimerism was investigated in recipients of VBMTx and skin grafts in blood, spleen, mesenteric lymph node, and bone marrow with the monoclonal antibody OX27 directed against MHC class I polymorphic RT1 on BN cells and quantitatively analyzed in a FACStar. In the VBMTx group, the free skin flap survived 70 days after weaning off cyclosporine A (CsA). An intravenous infusion of BMC in suspension equivalent to that grafted in the hind limb did not prolong skin graft survival after cessation of CsA therapy. Donor-derived cells could be detected in VBMTx recipients as long 70 days after weaning off CsA but not in recipients of i.v. suspension BMC grafting.

Animals↗
PubMed1998

The effect of cyclosporine on regulators of fibrinolysis in plasma from renal allograft recipients.

Fibrinolytic disturbances are thought to play an important role in processes leading to deterioration of renal allograft function. We investigated the effect of CsA therapy on the regulation of fibrinolysis in kidney graft recipients by measuring plasma concentration and activity of plasminogen activators (tPA, uPA) and their inhibitors (PAI-1, 2). We found an increase in tPA activity and in PAI-1 concentration as well as a decrease in PAI-1 activity in renal allograft recipients as compared to healthy controls, but did not confirm a correlation between these observations and CsA administration. tPA and PAI-2 concentrations as well as uPA activity did not significantly differ between the studied groups. We showed a significant decrease in uPA plasma concentration in patients treated with azathioprine. The significance of this finding is unknown.

Adult↗