Beta2-microglobulin (beta2M) is the light chain of the class I HLA molecule. The serum level of beta2M is elevated in various diseases including lymphoma, inflammation, viral infections and chronic renal dysfunction. The present study addressed the possible influence of beta2M on T lymphocyte activation in vitro. Peripheral blood mononuclear cells from a group of 17 healthy subjects were examined. Stimulation with OKT3 and fibronectin in combination with 30 mg beta2M/dl resulted in a two-fold increase of cell proliferation. A similar effect was observed when OKT3 and collagen I were applied as well as when OKT3 and collagen IV were used as costimulation to T cells. The CD69 expression, measured by flow cytometry was significantly enhanced above the control level (1.52 +/- 1.03% vs 33.21 +/- 20.26%, p<0.01, control group and 30 mg beta2M/dl, respectively). Together, these observations suggest that beta2M may play a role in modulating lymphocyte proliferation, possibly through modification of the CD69 molecule.

Adolescent↗

PubMed2001

[Selected parameters of antioxidant capacity in renal allograft recipients].

UNLABELLED: Various oxidant species, oxygen free radicals (OFR) implicated in patients with chronic renal diseases treated with dialysis and after cadaveric renal transplantation. Oxidative stress occurs when free radical generation exceeds antioxidant defence. We therefore examined markers of lipid peroxidation and antioxidant potential in blood (serum, plasma, RBC) of very carefully (clinically and biochemically) selected 102 subjects (56 female and 46 male, mean age 37.5 +/- 7 years). Included were 51 renal allograft recipients (RARs); 15 patients with glomerulopathies (GL); 36 healthy age- and sex-matched volunteers as a control group (C). All RARs were divided into two subgroups: RARs-A (n = 28) were treated with triple drug therapy including cyclosporin A (CsA) and RARs-Z (n = 23) were on double drug regimen: prednisone, azathioprine. Patients with coronary artery disease (CAD), diabetes, serum creatinine concentration > 2.0 mg/dl, acute rejection and infections were excluded. We used several automated assays to estimate: malondialdehyde (MDA); total radical-trapping antioxidant potential (TRAP), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), vit. E and lipid profiles. Patients of RARs-A were found to have significantly elevated triglycerides; cholesterol-LDL; MDA; TRAP and decreased activity of RBC glutathione peroxidase as compared with those of RARs-Z and group C. IN CONCLUSION: our data show that oxidative stress (with prooxidant effect of CsA partly at least), with reduced in antioxidant potential of defences system is associated with kidney transplantation.

Adult↗

PubMed2001

[Evaluation of patients for liver transplantation].

The liver transplantation (ltx.) is currently the only efficient treatment of the diseases which lead to the end stage liver failure. The proper time to perform the operation and the evaluation of the survival time, with or without transplantation, are the most important aspects of qualifications to the liver transplantation. There are no specific criteria of patient qualification for liver transplantation and there are no objective quantitative liver function tests. There were created many prognostic models for evaluation patients with chronic liver diseases. Some of them, the most popular, are presented in this article. We assume, that probability of one year survival less than 90% is the indication for ltx. However, the most important is total evaluation of clinical condition of the patient with liver failure. Such a complicated problem like qualification patients for ltx. needs to be solved by a team of experts from different medical specializations.

Humans↗

PubMed2001

Protease administration decreases enhanced transforming growth factor-beta 1 content in isolated glomeruli of diabetic rats.

Overproduction of transforming growth factor (TGF)-beta 1 messenger RNA is of fundamental importance in the pathogenesis of diabetic nephropathy. In vitro studies have recently shown that the serine protease trypsin diminishes the enhanced TGF-beta 1-expression induced by advanced glycation end products. Moreover, proteolytic enzymes may accelerate the removal of TGF-beta 1 from renal tissue via a protease-induced activation of alpha 2-macroglobulin (alpha 2M). This activation results in the binding of numerous cytokines, including TGF-beta 1 and is followed by enhanced plasma clearance of the protease alpha 2M-cytokine complex. In the present study in streptozotocin-diabetic rats we investigated whether the administration of Phlogenzym, a fixed combination of the proteases trypsin and bromelain combined with the antioxidant rutosid, modulates renal hypertrophy and the formation of TGF-beta 1 in isolated glomeruli. Three weeks after induction of diabetes, renal hypertrophy developed with an enhanced kidney/body weight ratio. When compared with normal rats, an elevated content of intraglomerular TGF-beta 1 (44.25 +/- 21.9 vs. 71.1 +/- 23.4 ng/microgram DNA, p < 0.05) as well as fibronectin (2.62 +/- 0.49 vs. 3.42 +/- 0.62 ng/microgram DNA, p < 0.05) was observed. In the diabetic rats, treatment with intraperitoneal proteases prevented the rise of intraglomerular TGF-beta 1 content (34.9 +/- 22.2 ng/microgram DNA, p < 0.01) and attenuated the rise of fibronectin (3.03 +/- 1.12 ng/microgram DNA NS). Furthermore, a decrease in the kidney/body weight ratio (p < 0.01) was achieved. Protease administration did not affect blood glucose concentration and was without visible adverse effects.

Animals↗

PubMed2001

[Induction of the immune tolerance--clinical trials].

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Animals↗

PubMed2000

Randomised open clinical trial of conversion from mycophenolate mofetil to azathioprine in cadaveric renal transplantation.

Mycophenolate mofetil (MMF) is a powerful immunosuppressive drug with established efficacy and safety. The search for a less expensive immunosuppressive protocol has led to an open randomised clinical trial of conversion from MMF to azathioprine (Aza). A total of 28 renal allograft recipients treated with prednisone, cyclosporine, and MMF was randomised into two groups: converted (early conversion) and control (late conversion). Conversion from MMF to Aza was conducted at the end of the 4th post-transplant month in the converted group and after the 12th month in the control. During the 20-month observation period, biopsy-proven acute rejection occurred more frequently in the converted than in the control group, although the difference was not statistically significant. Early conversion from MMF to Aza increased the risk of subsequent rejection in those patients who underwent at least one episode of acute rejection prior to conversion.

Adult↗

PubMed2000

Mechanism of antinephritic effect of proteinase inhibitors in experimental anti-GBM glomerulopathy.

We have previously documented amelioration of rat autologous anti-GBM nephritis with the antiproteolytic drugs epsilon-aminocaproic acid (EACA) and aprotinin, given from the day of induction or later in the course of disease. In the present study we investigated potential mechanisms of this effect by assessing interactions of the drugs with proteinase-dependent generation of superoxide anion in glomeruli, and their influence on both GBM degradation in vitro and activity of glomerular proteolytic enzymes. Release of O2- by enzymatically disrupted glomeruli, isolated from nephritic control or EACA/aprotinin-treated rats, was measured with the ferricytochrome reduction method and its activity was correlated with proteinuria and glomerular cellularity at the early phase of the disease. The hydroxyproline release assay was used to quantitate degradation of rat GBM in vitro by leukocyte proteinases stimulated by phorbol myristate acetate (PMA), in the presence or absence of EACA and aprotinin. Finally, the activities of elastase, cathepsins B and L, and plasmin, together with collagenase-like activity, were assessed fluorimetrically in homogenates of glomeruli isolated from control and antiproteolytic-drug-treated nephritic rats. EACA and aprotinin notably inhibited production of superoxide by nephritic glomeruli (by 47% and 66%, respectively), and this effect was not significantly correlated with proteinuria or glomerular hypercellularity at the early stage of disease. On the other hand, generation of O2- by glomeruli of untreated nephritic rats was notably correlated with total glomerular cell counts and numbers of macrophages infiltrating glomeruli. PMA-stimulated neutrophils and macrophages caused degradation of isolated rat GBM in vitro, markedly attenuated in the presence of EACA (P<0.0005) and, to a lesser extent, by addition of aprotinin (P<0.01). The activity of elastase was significantly reduced in glomeruli of nephritic rats treated with EACA or aprotinin (both P<0.001), while activities of remaining proteinases were not appreciably affected. The beneficial influence of proteinase inhibitors on rat anti-GBM disease may be due, at least in part, to abrogation of superoxide generation in nephritic glomeruli. EACA and aprotinin also have potential to interfere with digestion of GBM, and both these effects may be related to suppression of glomerular elastase.

Aminocaproic Acid↗

PubMed2000