The influence of angiotensin-converting enzyme gene of donor and recipient on the function of transplanted kidney.

One of the genes that is supposed to influence renal graft function is the one encoding angiotensin I-converting enzyme (ACE). It shows polymorphism in the presence (I allele) or absence (D allele) of a 287-base pair fragment. The question arises whether ACE gene polymorphism of the recipient and donor influences renal graft survival. This prospective study included 94 recipients who underwent ACE genotyping (DD, DI, II) and measured their creatinine clearance after cimetidine administration. These factors were correlated with the occurrence of acute or chronic rejection and of pharmacologic treatment of hypertension. In 27 recipients it was possible to obtain the ACE genotype of the donor. Among the recipients, 36 proved to be DD genotype, 38 ID, and 20 II. Among the donors, 10 proved to be DD genotype, 10 ID, and 7 II. The changes in creatinine clearance after cimetidine administration were not significantly different among any of the genotype subgroups. Significantly higher creatinine concentrations were found among recipients with II genotype compared to the combined group of ID and DD among patients not treated with ACE inhibitors, but not among those receiving ACE I after kidney transplantation. No differences were found in the frequency of rejection episodes among the subgroups with different ACE genotypes. No significant influence of donor ACE genotype on renal graft function was observed. In summary, the I/D genotype was not an independent prognostic factor for renal graft survival in the first 4 years after transplantation. Possibly the use of ACE I alters the influence of genotype on some parameters.

The influence of oxidative stress on permeability of capillary vessels in the cheek pouch of hamsters with alloxan-induced diabetes.

BACKGROUND: The aim of the study was to assess the influence of oxidative stress on the increase of permeability of capillary vessels in animals with alloxan-induced diabetes. MATERIAL AND METHODS: The studies were performed in microcirculation system of hamster cheek pouch. After the blockade of histamine receptors and administration of diamine oxidase (DAO) and histamine into circulation fluorescein angiography was done. In addition, the influence of superoxide dismutase, aminoguanidine (DAO inhibitor) and trascolan (protease inhibitor) on vascular permeability caused by superoxide radical generation in DAO/histamine system was assessed. RESULTS: The number of extravasal leakages in the group receiving HA and DAO was significantly higher (p < 0.001) than in the groups receiving potential vascular "sealers", e.g. SOD, aminoguanidine or trascolan. In the group receiving aminoguanidine the number of leakages was significantly lower (p < 0.05) compared to the group receiving SOD or trascolan. CONCLUSIONS: The protective effect of aminoguanidine, superoxide dismutase or trascolan decreasing the vascular permeability, suggests that the increased vascular permeability is a result of superoxide radical generation by diamine oxidase.

[Analysis of HLA class I and II antigens composition in high-risk pregnancy]. / Analiza wystepowania antygenów HLA klasy I i II w ciazy wysokiego ryzyka.

DESIGN: We have analyzed the frequency of HLA class I and II antigens in high-risk pregnancy. MATERIAL AND METHODS: Altogether, 22 gravida hospitalized at the Department of Pathology of Pregnancy and Labour, Pomeranian Medical University in Szczecin formed group I (PE) with 12 cases of preeclampsia and group II with 10 cases of the antiphospholipid syndrome (APS). The control group included 40 multigravida. Typing of HLA class I and II antigens was done using the two-stage microcytotoxic test (NIH) of Mittal. RESULTS: Antigen B35 was found more frequent in preeclampsia and antiphospholipid syndrome groups than in multigravida. Furthermore, a statistically significant difference in the frequency of homozygotes for the HLA-DR locus was noted between groups PE and APS on one hand, and controls on the other. CONCLUSIONS: Identical HLA-DR3, DR4 and DR5 antigens were found more frequently in preeclampsia, while identical DR4 and DR6 in the antiphospholipid syndrome.

Soluble HLA-DR and soluble CD95 ligand levels in pregnant women with antiphospholipid syndromes.

Antiphospholipid syndrome (APS) is a severe complication in pregnancy that can lead to fetal death in the second or third trimester. As soluble HLA-DR (sHLA-DR) molecules are reported to be implicated in the etiology of pregnancy disorders and of autoimmune diseases, we studied sHLA-DR plasma levels in pregnant women with APS (n = 14) and in women with normal pregnancy (n = 15), in women with high-risk pregnancies such as preeclampsia (PE; n = 20) and intrauterine growth retardation (IUGR; n = 10) and in fertile non-pregnant women (n = 29). The sHLA-DR levels of pregnant women were assessed during the third trimester, at labor, in the first week, and in the third month of puerperium. The results obtained were compared with soluble CD95 ligand (sCD95L), an important signal molecule in the apoptosis pathway. The sHLA-DR levels in pregnant women with APS were approximately three times higher (mean 1.48 +/- 0.15 microg/ml) during the whole observation period than in fertile non-pregnant women (0.54 +/-.06 microg/ml) and nearly double in women with high risk (PE, 0.91 +/- 14 microg/ml; IUGR, 0.94 +/-.21 microg/ml) and in normal pregnancies (0.74 +/- 0.13 microg/ml). Furthermore, sHLA-DR levels of pregnant women with APS were positively correlated with the serum concentration of anti-anticardiolipin immunoglobulin G antibodies. For sCD95L plasma levels, no substantial variations were found among the different groups above. In pregnant women with APS, however, sHLA-DR levels were positively correlated with sCD95L levels. Further studies should clarify the functional involvement of sHLA-DR molecules in the induction of CD95/CD95L-mediated apoptosis pathway that may play a crucial role in the pathology of pregnancies complicated by APS.