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Biomedical subjects

L Paczek

Publications and source records attributed to L Paczek.

At least 109 records · Page 6Linked to original sources
PubMed1996

Beneficial effect of proteases on allograft arteriosclerosis in a rat aortic model.

Recently it has been shown that protease therapy ameliorates certain immune-mediated diseases. Thus we studied the effect of administration of a protease mixture on aortic transplant arteriosclerosis in rats. Segments of abdominal aorta from SHR strain were transplanted orthotopically into WKY recipients. Two groups of allografted rats were used. One group (n = 8) was treated with daily intraperitoneal injections of 12 mg of a protease formulation containing trypsin, bromelain and rutosid, and another group (n = 8) with placebo. Eight WKY rats were transplanted with syngenic aortas and treated with placebo. After 8 weeks, structural changes of the grafted segment were evaluated by morphometric analysis of formalin-fixed sections with specific stains. In untreated allografts there was a marked intimal thickening, medial necrosis with disruption of elastic fibres, and inflammatory infiltrates in the adventitia. Administration of proteases inhibited formation of neointima by 59.0% when cross-sectional areas were compared (80+/-11 versus 195+/-11 microm2, P<0.01; protease-versus placebo-treated allograft recipients respectively) and decreased medial injury as estimated by the integrity of elastic fibres and smooth-muscle cell density. Thus, in an experimental model of rat aortic allograft, protease administration ameliorates rejection-induced arterial wall remodelling.

Animals↗
PubMed1996

Impaired proteolytic activity as a potential cause of progressive renal disease.

Renal hypertrophy (an increase in cellular protein content and cellularity as well as an accumulation of extracellular matrix) is due to the imbalance between protein synthesis and degradation. Proteolytic activity in the kidney plays an important role in maintaining this balance. Impaired renal proteolytic activity caused by such factors as high protein intake, metabolic acidosis, angiotensin II and transforming growth factor-beta 1 in vivo and in vitro may result in decreased protein degradation and subsequent induction of cellular hypertrophy, even in the absence of increased protein synthesis.

Acidosis↗
PubMed1996

Low-density lipoprotein suppresses cathepsins B and L activity in rat mesangial cells.

Disturbances of lipid metabolism are considered to play a pathogenetic role in glomerulosclerosis. Since intraglomerular have been proposed to be involved in the pathogenesis of the glomerulosclerosis, we have investigated the influence of LDL on the activity of the cellular proteases. Cathepsins B and L were measured with the aid of fluorometry, and 7-amido-4-methylocoumarin derivates were used as substrates; Z-Arg-Arg-AMC for cathepsin B, Z-Phe-Arg-AMC for cathepsins B and L together. Rat mesangial cells cultured 24 h in medium supplemented with LDL revealed inhibition of cathepsin B activity at concentrations of 250 micrograms LDL/ml medium, lower LDL concentrations were without apparent effect. Since the glomerular accumulation of structural and nonstructural proteins plays an important role in glomerulosclerosis, we conclude that the augmented proteolytic activity of mesangial cells might be one of the pathways located by which hyperlipidemia causes an increased susceptibility to glomerular damage.

Animals↗
PubMed1996

[Increased urinary excretion of transforming growth factor beta and interleukin-6 in patients with diabetic nephropathy].

The purpose of the study was to assess TGF-beta and IL-6 urinary excretion (measured with EIA) in 12 IDDM patients (7 F, 5 M, age 20-49 yrs, mean = 33.08) with albuminuria or microalbuminuria. Control group consists of 27 IDDM patients (12 F, 15 M, age 24-59 yrs. mean = 39.5) without albuminuria or microalbuminuria. Urinary excretion of IL-6 was significantly higher (p < 0.05) in IDDM patients with albuminuria (mean = 7.43 +/- 8.29 pg/mg creatinine) than in control group (mean = 3.74 +/- 2.64 pg/mg creatinine). Urinary excretion of TGF-beta was also higher (but not significantly in IDDM patients with albuminuria or microalbuminuria (mean = 42.0 +/- 30.0 pg/mg creatinine) than in control group (mean = 27.0 +/- 20.0 pg/mg creatinine). The data indicate that IL-6 and TGF-beta could be involved in the development of diabetic nephropathy.

Adult↗
PubMed1996

Erythropoietin production after kidney transplantation.

We studied production of erythropoietin (EPO) in long-term renal allograft recipients with posttransplant erythrocytosis (PTE). Among 951 recipients we found 74 patients with persistent elevation of hematocrit (Htc) value (female > 50%, male > 55%). However, only 63.5% of them had increased red-cell mass ( = "true" erythrocytosis). In all recipients with PTE known causes of secondary erythrocytosis were not found. EPO titer in peripheral blood was significantly higher in recipients with PTE (median 13.5 mIU/mL, range: 0.1-71.5 mIU/mL) as compared to healthy blood donors (median 5.75 mIU/mL, range: 0.1-19.5 mIU/mL) but not different from the group of renal allograft recipients without PTE (median 13.0, range 0.1-71.7 mIU/mL). However, EPO level measured in pretransplant sera was significantly higher in patients who developed PTE (median 16.4 mIU/mL, range: 1.0-281.2 mIU/mL) than in recipients without PTE (median 8.3, range: 1.0-50.3 mIU/mL). A significant difference in EPO level between systemic and effluent blood from native kidneys was found in 6 out of 14 recipients with PTE who underwent catheterization. After phlebotomy patients with PTE responded with higher increase in peak EPO titer than healthy blood donors (527 +/- 473% versus 194.5 +/- 44.2%, p < 0.05). Our results suggest that PTE develops spontaneously due to increased EPO production. Despite elevated EPO levels, regulation of EPO release remains preserved.

Adult↗
PubMed1996

Intraglomerular fibronectin and laminin turn-over in chronically rejected kidney allografts in humans.

Chronic rejection is primarily responsible for the late loss of allografted organs and remains an important clinical problem. Chronic rejection in the kidney is characterised by arteriolosclerosis and nephrosclerosis, glomerulonephritis and interstitial fibrosis. Recently, a large number of studies have indicated that proteolytic enzymes play important roles as mediators of glomerular injury. The aim of the study was to assess intraglomerular fibronectin and laminin contents as well as cysteine proteinases in activity chronically rejected human kidneys. We investigated kidney tissue from graftectomy specimens obtained from 11 patients with end-stage renal disease following chronic rejection. A group of 9 patients undergoing nephrectomy because of cancer served as a control group, but only not involved parts of the kidneys were used. When intraglomerular laminin contents were related to DNA content, significant accumulation in chronically rejected allografts was found in comparison to controls (382 +/- 171 micrograms per microgram DNA and 190 +/- 82 micrograms per microgram DNA, respectively, p < 0.01. The accumulation of fibronectin was higher than in controls, however the difference was not significant. When proteinase activity was related to intraglomerular DNA content, significantly enhanced cathepsin B and L activity was found in rejected kidney allografts (57 +/- 16 nmol AMC/min per mg DNA) in comparison to controls (15 +/- 2 nmol AMC/min per mg DNA). Summarizing, we observed accumulation of fibronectin and laminin in glomeruli and simultaneously an excess of proteolytic activity in human chronically rejected kidneys. The above phenomenon indicates that a very active metabolic process takes place in glomeruli during rejection.

Adult↗
PubMed1995

Dose-dependent stimulation/inhibition effects of cyclosporin A on lysosomal cathepsin activities in cultured proximal tubule cells.

The effects of cyclosporin A on the activities of lysosomal cysteine proteinases (cathepsin B, H, L+B) in LLC-Pk1 cells were investigated to elucidate their potential role in cyclosporin A-induced nephrotoxicity. Cyclosporin A at lower doses (0.1--1,000 ng/ml) stimulated cathepsin B, H, L+B. In contrast, at a higher dose (10,000 ng/ml), it inhibited these proteinase activities associated with a reduction in protein degradation. In line with the altered proteinase activities, cellular protein content was decreased at the lower dose (10 ng/ml) and increased at the higher dose. The higher dose of cyclosporin A also enhanced cellular lipid peroxide content after an exposure of 4 and 10 h. Co-incubation with superoxide dismutase (40 U/ml) did not ameliorate the inhibition of cathepsin B activity induced by the high dose of cyclosporin A. On the contrary, the calcium channel blocker verapamil (10(-6) M) prevented this inhibition. In conclusion, cyclosporin A exerts a dose-dependent biphasic effect on lysosomal cysteine proteinase activities. A rise in cytosolic Ca2+ concentration, but not an enhanced lipid peroxidation, may be involved in the suppression of cathepsin B activity induced by the higher dose of cyclosporin A. These studies raise the possibility that alterations of tubular proteinase activity may play a role in the cyclosporin A-induced nephrotoxicity.

Calcimycin↗