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L Paczek

Publications and source records attributed to L Paczek.

At least 37 records · Page 2Linked to original sources
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↗
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

Usefulness of hybridization and PCR methods in monitoring of CMV infection in renal transplant recipients.

The purpose of this work was to compare hybridization and PCR methods as diagnostic tests in diagnosing and monitoring CMV infection. The investigation was performed in a group of 24 renal transplant recipients treated with ATG. The results we obtained suggest that quantitative variant of hybridization is more useful in diagnosing the infection than PCR, because it enables to monitor the infection. DNA CMV level of about 60 pg/ml or the increasing level in the subsequent samples should be a sign to start antiviral therapy.

Adult↗
PubMed2000

Liver transplantation in the experience of the centre commencing the program.

From 1989 to 1999, 43 orthotopic liver transplantations (OLT) in 40 patients (3 retransplantations) were performed in our Department. The most common indications for OLT were noninflammatory, primary cholestatic liver diseases and postinflammatory liver cirrhosis. Fourty OLT's were done for elective indications, three--on emergency basis, because of fulminant liver failure. The majority of transplantations was performed with classical technique with the excision of retrohepatic vena cava and routine use of the extracorporeal veno-venous bypass. Only in 4 patients the piggyback technique was used and performed without temporary portocaval anastomosis. All 3 patients transplanted for fulminant liver failure died in the perioperative period. Twenty four patients are still alive and well, the longest period of observation exceeding 5 years.

Humans↗
PubMed2000

[The importance of advanced glycosylation end products in the creation and progression of atherosclerosis in non-insulin-dependent diabetes mellitus].

Diabetic macroangiopathy is a major cause of morbidity and mortality of patients with non-insulindependent diabetes mellitus. Bad metabolic control of diabetes increases the risk of developing atherosclerotic complications. Hyperglycemia aids to increase the process of non-enzymatic protein glycosylation. Advanced glycation end products (AGEs) created in Maillard reaction play multidirectional role in creation of atherosclerosis in NIDDM. AGEs form in LDL, HDL and VLDL particles and increase their oxidative modification. They aid deposition of cholesterol and its esters in macrophages as well as creation of foam cells. Reaction of LDL-AGE particles with proteoglycans of blood vessel intima results in its thickening. LDL-AGE and ox-LDL take part in formation of late atherosclerotic changes influencing the expression of genes for cytokines and growth factors. AGEs promote prothrombotic changes. They block formation of nitric oxide which results in impaired vessel relaxation. They also take part in progressive vessel narrowing up to complete vessel occlusion by atheroslerotic plaque.

Arteriosclerosis↗