Hemolytic uremic syndrome caused by verotoxin-producingEscherichia coli O26

Verotoxin-producing Escherichia coli (VTEC) are nowadays among the most important emerging group of food-borne pathogens (VTEC strains cause gastroenteritis that can be complicated by the hemorrhagic colitis or hemolytic uremic syndrome, HUS). Escherichia coli 026 producing verotoxin 2 was isolated and its identity confirmed by examination of phenotype and genotype; the strain was first described in Slovakia in association with the development of HUS in a 4-year-old girl.     

Hemolytic uremic syndrome following the infusion of oxaliplatin: case report

Background  

Oxaliplatin is a platinum derivative, which is used in the treatment of colorectal cancer. A small number of oxaliplatin-related hemolytic and/or thrombocytopenic reactions have been reported. We present a case of hemolytic-uremic syndrome that developed during the 4^th cycle of combination chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin.     

Genotoxic potential of cyclosporin A in patients with renal transplantation

We analyzed the induction of sister chromatid exchange (SCE) by cyclosporin A (CsA) as a marker of genotoxic potential. In 30 patients undergoing renal transplantation, SCE induction was tested before the introduction of CsA and 3 months later. We found that SCE frequency increased significantly at the end of 3 months. To our knowledge, this is the first study demonstrating in vivo induction of SCE by CsA in humans. We conclude that CsA has a genotoxic potential on human lymphocytes.     

Interferon in patients with hemorrhagic fever with renal syndrome

The in vitro production of alpha- and gamma-interferon (IF) by peripheral blood lymphocytes (PBL) and the concentration of serum IF in 50 patients having hemorrhagic fever with renal syndrome (HFRS), as well as the possibility of the formation of spontaneous IF by PBL and the influence of the patient blood plasma on alpha-IF genesis, was studied. The development of HFRS was accompanied by a rise in the level of serum IF with different speed, depending on the severity of the disease with simultaneous suppression of the lymphocytes capacity for alpha- and especially gamma-IF production. In cases of moderate and severe forms of the disease no restoration of the IF system occurred by the moment of discharge from the hospital. In a few patients spontaneous IF in low titers was determined. In cases of the moderate form of the disease in the oligoanuretic period and the severe form of the disease in the oligoanuretic and polyuretic periods the patients' blood plasma essentially suppressed the production of alpha-IF by PBL.     

Ability of granulocytes to reduce nitroblue tetrazolium in uremic patients treated conservatively

NTB reduction test, both spontaneous and stimulated with E. coli endotoxin, was performed in peripheral blood granulocytes of 40 individuals of both sexes aged between 18 and 64 years treated conservatively at the nephrologic outpatient clinic. Serum creatinine, urea and uric acid were assayed at the same time. A control group included 40 healthy individuals of both sexes aged between 20 and 56 years. Statistically significant increase in spontaneous reduction of NTB was achieved in the group of the uremic patients in comparison with the control group. Moderately positive correlation between creatinine level and percentage of NTB-positive cells in the spontaneous test was shown. Possibility of granulocyte stimulation by uremic toxins is being considered.     

Oxylipin profiling of human plasma reflects the renal dysfunction in uremic patients

Introduction

Nearly all the enzymes that mediate the metabolism of polyunsaturated fatty acids (PUFAs) are present in the kidney. However, the correlation of renal dysfunction with PUFAs metabolism in uremic patients remains unknown.

Objectives

To test whether the alterations in the metabolism of PUFAs reflect the renal dysfunction in uremic patients.

Methods

LC–MS/MS-based oxylipin profiling was conducted for the plasma samples from the uremic patients and controls. The data were analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The receiver operating characteristic (ROC) curves and the correlation of the estimated glomerular filtration rate (eGFR) with the key markers were evaluated. Furthermore, qPCR analysis of the whole blood cells was conducted to investigate the possible mechanisms. In addition, a 2nd cohort was used to validate the findings from the 1st cohort.

Results

The plasma oxylipin profile distinguished the uremic patients from the controls successfully by using both PCA and OPLS-DA models. 5,6-Dihydroxyeicosatrienoic acid (5,6-DHET), 5-hydroxyeicosatetraenoic acid (5-HETE), 9(10)-epoxyoctadecamonoenoic acid [9(10)-EpOME] and 12(13)-EpOME were identified as the key markers to discriminate the patients from controls. The excellent predictive performance of these four markers was validated by ROC analysis. The eGFR significantly correlated with plasma levels of 5,6-DHET and 5-HETE positively but with plasma 9(10)-EpOME and 12(13)-EpOME negatively. The changes of these markers may account for the inactivation of cytochrome P450 2C18, 2C19, microsome epoxide hydrolase (EPHX1), and 5-lipoxygenase in the patients.

Conclusion

The alterations in plasma metabolic profile reflect the renal dysfunction in the uremic patients.

     

Pathology of modified graft-versus-host disease in bone marrow allografted monkeys treated with antilymphocyte serum.

Lethally irradiated rhesus monkeys were used for bone marrow allografting and autografting. Monkeys receiving allogeneic bone marrow developed acute graft-versus-host reaction (GVHR) and had a mean survival time of 9.1 days as compared to autografted monkeys which survived above 500 days. Treatment with antilymphocyte sera (ALS) before allografting modified the GVHR and extended the survival time to an average of 43 days. Histologically, such animals showed evidence of "chronic" GVHR and septicemia secondary to a lack in lymphoreticular recovery. Subsequently, severe GI-tract infections followed which usually served as portal of entry for septicemia.     

Evolution of alloantibodies and suppressor cells in allografted mice treated for passive enhancement

The kinetics and quality of the alloimmune reaction were studied in CBA (H-2k) mice treated for passive enhancement of tumor allografts (Sa 1 indigenous of A/J (H-2a or H-2k/d) mice). Serum samples of treated animals were tested for their biological properties relevant to different antibody isotypes in vitro (hemagglutination, complement-dependent cytotoxicity, and anaphylaxis, i.e., mast cell degranulation involving all main Ig isotypes; IgM, IgG2, and IgG1, IgE, respectively) as well as in vivo (allograft enhancement). Spleen cells from these treated animals were examined for their capacity to interfere with the rejection of tumor allografts by adoptive transfers into syngeneic recipients. In vitro, 51Cr release cytolysis assays were performed in order to test their cytolytic and regulatory activities in comparison to rejecting control animals. It has been shown that: grafted mice, pretreated for passive enhancement, kept their grafts longer and synthetized anaphylactic antibodies (mainly IgG1) earlier and at higher titers than normal serum controls, which rejected the same Sa 1 allografts. Mice with enhanced tumors synthetized cytotoxic antibodies (mainly IgG2) later than rejecting controls. Serum samples from treated and control animals, harvested 10 days (early sera) and 30 days (late sera) after grafting, were injected with a "normal dose" (0.2 ml) and a "high" dose (0.4 ml) to new CBA recipients grafted with Sa 1. Early immune sera were only enhancing at high doses when derived from animals previously treated for enhancement (at the low dose both immune sera were enhancing). Late sera, presenting both complement-fixing, cytotoxic (predominantly IgG2), and IgG1 anaphylactic alloantibodies in the two groups, induced enhancement in all cases, but more strongly when derived from the group treated for Sa 1 enhancement. Adoptive transfer of spleen cells from animals treated for passive enhancement were able either to inhibit the accelerated rejection (Day 10) or to promote enhancement of Sa 1 allogeneic cells (Day 30) while similar cells taken (Day 10 and Day 30) from control graft-rejecting mice transferred accelerated rejection. Among the transferred T-cell sub-populations, the suppressive effect was mediated by Lyt 2 T cells. In vitro, these spleen cells showed a weaker cytolytic activity than those of allograft-rejecting mice. Moreover, they were able to regulate the cytolytic activity of cytotoxic effector cells from specifically immunized CBA mice.     

Replacement of renal function in uremic animals with a tissue-engineered kidney.

Current renal substitution therapy with hemodialysis or hemofiltration has been the only successful long-term ex vivo organ substitution therapy to date. Although this approach is life sustaining, it is still unacceptably suboptimal with poor clinical outcomes of patients with either chronic end-stage renal disease or acute renal failure. This current therapy utilizes synthetic membranes to substitute for the small solute clearance function of the renal glomerulus but does not replace the transport, metabolic, and endocrinologic functions of the tubular cells. The addition of tubule cell replacement therapy in a tissue-engineered bioartificial kidney comprising both biologic and synthetic components will likely optimize renal replacement to improve clinical outcomes. This report demonstrates that the combination of a synthetic hemofiltration device and a renal tubule cell therapy device containing porcine renal tubule cells in an extracorporeal perfusion circuit successfully replaces filtration, transport, metabolic, and endocrinologic functions of the kidney in acutely uremic dogs.