Lack of association of polymorphisms 239+34A/C in the SOD1 gene and 47C/T in the SOD2 gene with delayed graft function and acute and chronic rejection of kidney allografts.

The superoxide dismutases (SODs) seem to be the most important enzymes involved in defense against reactive oxygen species, in particular against superoxide anion radicals. We hypothesized that genetic variability of antioxidant enzymes may have a role in development of these complications. The objective of the present study was to examine the association between polymorphisms 239+34A/C in the SOD1 gene or 47C/T in the SOD2 gene and development of delayed graft function (DGF) and acute or chronic rejection. The study included 187 recipients of first renal transplants. Patient history was analyzed taking into account DGF, acute rejection episodes, and chronic rejection. The polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. There were no significant associations between the polymorphisms and DGF or acute or chronic rejection. Our findings suggest that polymorphisms in SOD1 and SOD2 are not associated with development of either DGF or acute or chronic rejection.

Circulating adhesion molecules during kidney allograft reperfusion.

Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant recipients, including 13 cases of delayed graft function (DGF) and 11 cases of acute graft rejection (AR). Plasma concentrations of E-selectin, VCAM-1 and ICAM-1 after 3 min of reperfusion were significantly higher than in the iliac vein before reperfusion. There was no statistically significant difference between patients with and without DGF as regards E-selectin, VCAM-1 and ICAM-1 concentrations in the iliac vein before and in the renal vein after 3 min of reperfusion. Concentrations of adhesion molecules in the iliac vein before reperfusion and in the renal vein after 3 min of reperfusion did not differ significantly between patients with and without AR except for ICAM-1 iliac vein concentration which was significantly increased in AR patients. Plasma levels of E-selectin, ICAM-1 and VCAM-1 were increased after kidney allograft reperfusion. Moreover, elevated serum levels of ICAM-1 before transplantation correlated with subsequent acute kidney allograft rejection. The results suggest that elevated ICAM-1 levels may be implicated in acute graft rejection.

IL-2 and TNF-alpha promoter polymorphisms in patients with acute kidney graft rejection.

INTRODUCTION: Proinflammatory cytokines have been implicated in the pathogenesis of acute kidney allograft rejection. The aim of the study was to examine the association between interleukin (IL)-2 -330 and tumor necrosis factor (TNF)-alpha -308 promoter polymorphisms and acute kidney allograft rejection. METHODS: The study included 72 patients with long-term stable graft function, and 57 diagnosed with acute kidney allograft rejection. RESULTS: Patients with acute kidney allograft rejection showed a prevalence of subjects with TNF-alpha T2 allele (P < .05). The risk of acute kidney allograft rejection diagnosis was 2.5-fold greater among carriers of the T2 allele than those homozygous for T1T1 (OR 2.53, 95% CI 1.19 to 5.37, P < .05) There was no statistically significant difference in the distribution of IL-2 genotypes between patients with stable graft function and acute kidney allograft rejection. CONCLUSION: The results suggest that TNF-alpha-308 promoter polymorphism is a risk factor for acute kidney allograft rejection.

The cytokine gene polymorphisms in patients with chronic kidney graft rejection.

Chronic allograft rejection remains an important cause of morbidity after kidney transplantation. The aim of the study was to examine the association between IL-2, IL-6 and TNF-alpha promoter polymorphisms and chronic kidney allograft rejection. The study included 64 patients with long-term stable graft function and 62 with chronic allograft nephropathy. Among patients with chronic allograft nephropathy a statistically significant prevalence of the IL-6 CC genotype associated with low IL-6 expression was observed (p < 0.01, OR 3.18; 95% CI 1.27-8.15). There were no statistically significant differences in distribution of IL-2 and TNF-alpha genotypes between patients with stable graft function and chronic allograft rejection. The results of present study suggest that the genetically determined low IL-6 production may be the risk factor of chronic allograft nephropathy development.

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.

The expansion of CD4+CD28- T cells in patients with chronic kidney graft rejection.

CD4+CD28- T cells are oligoclonal lymphocytes rarely found in healthy subjects, but are present in high frequencies in patients with inflammatory diseases. Contrary to paradigm, they are functionally active and produce interferon gamma and cytolytic proteins, are cytotoxic in vessels and may contribute to tissue damage. The size of the peripheral blood CD4+CD28- T cell compartments was determined in 20 healthy individuals, 20 patients after renal transplantation with stable graft function, and 20 with chronic graft rejection by two-color FACS analysis. In patients with stable graft function, the median frequency of CD4+CD28- T cells was 3.1% and was significantly higher in comparison to the control group (1.4%) (P <.01). The highest subset CD4+CD28- cells was detected in patients with chronic graft rejection (10.65%). The amount of CD4+CD28- cells was significantly higher in this group in comparison to patients with stable graft function (P <.01). The evaluated number of CD4+CD28- cells in patients after renal transplantation, especially in graft recipients with chronic graft rejection, suggests a role of these cells in chronic graft destruction.

Chlorpropamide toxicity with survival despite 27-day hypoglycemia.

CASE REPORT: In the past 5 years at our institution, 12 cases involving the ingestion of chlorpropamide 3-15 g were fatal. We report a 23-year-old woman with an estimated ingestion of chlorpropamide 5-10 g. Initial cardiovascular collapse, attributed to the blockade of potassium channel transport, responded to intensive support including 3 days of cardiac pacing. Urinary excretion of chlorpropamide and hypoglycemia persisted until day 27. The toxic mechanisms and high risk of chlorpropamide are summarized. A fatal therapeutic dose ratio as low as 4:1 has made this antidiabetic agent obsolete.

[The influence of hyperlipidemia on pharmacokinetics of free phenytoin]. / Wplyw hiperlipidemii na farmakokinetyke fenytoiny wolnej.

The problem of the effects of metabolic changes on drug pharmacokinetics is not yet sufficiently known. Phenytoin was used for the assessment of the effects of lipid profile disturbances on drug pharmacokinetics. Phenytoin is a lipophilic substance. It was shown that hyperlipidaemia changes phenytoin pharmacokinetics and the pattern of these changes depends on the type of hyperlipidaemia. In hypercholesterolaemia and in mixed hyperlipidaemia the blood level of free phenytoin was elevated. It should be remembered that hypercholesterolaemia and mixed hyperlipidaemia re conditions increasing the risk of phenytoin overdosage and this should be considered in establishing drug dosage.