Antioxidants in the treatment of patients with renal failure.

Renal failure is accompanied by oxidative stress, which is caused by enhanced production of reactive oxygen species and impaired antioxidant defense. The suggested therapeutical interventions aimed at reducing oxidative stress in chronic renal failure patients are as follows: 1) the use of biocompatible membranes, ultrapure dialysate, and removal of endogenous foci of infection; 2) haemolipodialysis, and electrolysed reduced water for dialysate preparation; 3) administration of antioxidants (alpha-tocopherol, ascorbic acid, N-acetylcysteine, reduced glutathione); 4) substances possibly affecting oxidative stress indirectly (erythropoietin, sodium selenite). As currently available data have, as yet, provided rather limited evidence for the clinical benefit of antioxidant interventions, at present it is untimely to give practical recommendations with regard to antioxidant treatment of patients with renal failure.

[Fibrohistiocytic sarcoma of the kidney (borderline malignancy)]. / Fibrohistiocytoma sarcomatosum renis (border line malignancy).

We described a case of 45 year old woman with left kidney tumour. In the pathological examination it appeared asa very seldom neoplasm--fibriohistiocytoma sarcomatosum. This lesion was accidentally diagnosed in ultrasound evaluation due to myomatous uterus observation in gynaecological hospital. There were no signs or symptoms of kidney tumour disease.

Lipid peroxidation and activities of antioxidant enzymes in the diabetic kidney: effect of treatment with angiotensin convertase inhibitors.

Effects of the angiotensin convertase inhibitors captopril (CAP) and enalapril (ENA) on the malondialdehyde (MDA) content and the activities of superoxide dismutase (SOD) and catalase in the kidneys of rats with streptozotocin-induced diabetes were studied. Induction of diabetes resulted in an increase of MDA concentration and progressive decreases of SOD and catalase activities after 6 and 12 weeks. CAP and ENA administration did not affect body weight changes or blood glucose and HbA1c contents in diabetic rats but decreased albuminuria and kidney weight increase, attenuated lipid peroxidation, and prevented the decreases in SOD and catalase activities. These results confirm the oxidative stress in streptozotocin-induced experimental diabetes and point to the beneficial antioxidant effects of angiotensin convertase inhibitors.

Synthesis and immunomodulatory activity of novel analogues of human beta-casein fragment [54-59].

Three novel analogues of human beta-casein fragment [54-59] have been synthesized and tested for their immunomodulatory activity. Interestingly, human beta-casein fragment [54-59] has been found to be increased nitric oxide release from neutrophils. The obtained analogues have shown less immunomodulatory activity than native hexapeptide.

Priming effect of met-enkephalin and beta-endorphin on chemiluminescence, chemotaxis and CD11b molecule expression on human neutrophils in vitro.

The opioid peptides are widely distributed throughout the body, and they are generated during stress and inflammatory reaction. Opioids are involved in the communication between the immune and neuroendocrine systems. In the present study we have investigated the ability of both met-enkephalin and beta-endorphin to stimulate and prime the human neutrophils for enhanced chemiluminescence (CL) and chemotaxis induced with fMLP, OZ or PMA. We have also tested the effect of beta-endorphin and met-enkephalin on CD11a, CD11b, CD18 and CD16 molecule expression on PMN in vitro. PMN from ten healthy donors were incubated in vitro with different concentrations of beta-endorphin or met-enkephalin, and the CL response was evaluated with luminometer. To assess the effect of opioid peptides on CD11a, CD11b, CD18 and CD16 molecule expression the whole blood samples were incubated with different concentrations of the opioids, then the white cells were labelled with respective PE-conjugated MoAb and evaluated by flow cytometry. We have shown that: (1) met-enkephalin and beta-endorphin at physiological concentrations relevant to that of in vivo (10(-8) and 10(-6) M) enhanced fMLP, PMA or OZ stimulated chemiluminescence and induced chemotactic response, (2) High concentrations of beta-endorphin (10(-3) M) or met-enkephalin (10(-5) M) decreased the CL response of PMN in vitro, (3) The opioid peptides at lower concentrations resulted in CD11b and CD18 molecule up-regulation on neutrophils. We may conclude that opioid peptides in physiological concentration are involved in neutrophil priming whereas in higher concentration exert immunosuppressive potency. Opioid peptides like inflammatory cytokines may prime the neutrophils inflammatory response.

Effect of aminoguanidine on erythrocyte lipid peroxidation and activities of antioxidant enzymes in experimental diabetes.

The effect of aminoguanidine (AG) on the malondialdehyde (MDA) concentration and activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in erythrocytes of rats with streptozotocin-induced diabetes was studied. Induction of diabetes resulted in an increase of MDA concentration and decreases of SOD and catalase activities after 6 and 12 weeks. GSH-Px activity increased after 6 weeks and returned to control values after 12 weeks. AG administration did not affect body weight, blood glucose level and HbA1c content in diabetic rats but led to a decrease of MDA concentration and SOD and catalase activities after 12 weeks of treatment, with no significant effect after 6 weeks. AG attenuated the GSH-Px increase after 6 weeks but augmented the activity of this enzyme after 12 weeks. These results confirm the presence of oxidative stress in streptozotocin-induced experimental diabetes and point to the beneficial antioxidant effect of AG.

Effect of aminoguanidine on lipid peroxidation and activities of antioxidant enzymes in the diabetic kidney.

The aim of this study was to examine lipid peroxidation and activities of key antioxidant enzymes in kidneys of rats with streptozotocin (STZ)-induced diabetes and the effect of aminoguanidine on diabetes-induced alterations. Three groups, 6 rats each, were studied: control animals, not treated diabetic rats and rats treated with aminoguanidine (AG; 1 g/liter of drinking water). After 6 and 12 weeks the animals were sacrificed and lipid peroxidation products and activities of antioxidant enzymes were determined in their kidney homogenates. Malondialdehyde (MDA) content was significantly elevated and activities of SOD and catalase decreased in the kidneys of STZ-diabetic rats. AG treatment attenuated the increase in MDA content and diminutions of activities of SOD and catalase in the kidneys of diabetic rats. These results confirm oxidative stress in the kidney of rats with STZ diabetes and point to an antioxidant effect of AG in experimental diabetes.

Lipid peroxidation and activities of antioxidant enzymes in erythrocytes of patients with non-insulin dependent diabetes with or without diabetic nephropathy.

BACKGROUND: Diabetes is known to involve oxidative stress. However, data on oxidative stress in diabetic nephropathy is scant. The aim of this study was to examine lipid peroxidation and activities of key antioxidant enzymes in non-insulin dependent diabetes (NIDDM) without nephropathy and in those with diabetic nephropathy. METHODS: Twenty-one NIDDM outpatients with obvious diabetic nephropathy (persistent proteinuria, over 0.5 g/day and albumin excretion over 200 microg/min), 14 NIDDM outpatients with a long diabetic history but without hypertension and with normal urinary albumin excretion rate (<20 microg/min) and 19 healthy persons were studied. Malondialdehyde (MDA) content of erythrocytes was quantified by HPLC according to Young et al. In erythrocytes, superoxide dismutase (SOD) activity was determined by the adrenaline method of Misra and Fridovich and catalase was estimated according to Beers and Sizer. RESULTS: MDA content was significantly elevated in erythrocytes of NIDDM patients without nephropathy vs the control group and even higher in erythrocytes of NIDDM patients with diabetic nephropathy. SOD and catalase activities were lower in erythrocytes of NIDDM patients without nephropathy than in the control group and lowest in erythrocytes of NIDDM patients with nephropathy. CONCLUSIONS: These results confirm oxidative stress in erythrocytes of NIDDM patients with nephropathy. The intensity of oxidative stress appeared to be greater than in NIDDM patients without nephropathy.

Effect of angiotensin convertase inhibitors on lipid peroxidation and peroxyl radical-trapping capacity in rats with experimental diabetes.

Effect of two angiotensin convertase inhibitors, enalapril and captopril, on blood plasma and erythrocyte lipid peroxidation and plasma peroxyl radical-trapping capacity was studied in rats with streptozotocin-induced diabetes. A progressive increase in blood erythrocyte malondialdehyde (MDA) level was observed in diabetic rats after 6 and 12 weeks. Blood plasma MDA level increased while plasma peroxyl radical-trapping capacity was decreased after 12 weeks. Captopril (2 mg/kg body weight) augmented the diabetes-induced changes in MDA content after 6 weeks and prevented them after 12 weeks increasing also the peroxyl radical-trapping capacity. Enalapril (1 mg/kg body weight) counteracted the diabetes-induced changes in MDA content after both 6 and 12 weeks but did not affect the plasma peroxyl radical-trapping capacity. These results suggest a possibility of a therapeutic use of angiotensin convertase inhibitors to attenuate the effects of oxidative stress in diabetes.

[The "Bizzare" leiomyoma in histopathological examination of the uterine myoma: dilemma of the range of operative treatment]. / "Bizzare" leiomyoma w badaniu histopatologicznym miesniaka trzonu macicy--dylemat zakresu leczenia operacyjnego.

The very rare case of leiomyoma sarcomatosum was presented and differentiated to "bizzare" leiomyoma at 39 years old woman, who was conservative preoperation diagnosis of uterine myoma. To get the after-operation prognosis the following elements of tumour have been studied: mitotic index, presence and type of necrosis, separation of the tumour and perivascular infiltration. A decision of conservative treatment was confirmed by shown world wide literature.

Effect of aminoguanidine on the generation of superoxide anion and nitric oxide by peripheral blood granulocytes of rats with streptozotocin-induced diabetes.

The effect of aminoguanidine (AG) on the production of superoxide anion O2*- and nitric oxide (NO) by peripheral blood granulocytes of rats with streptozotocin-induced diabetes was studied. Induction of diabetes resulted in an increase of O2*-. Generation by both unstimulated and opsonized zymosan-stimulated granulocytes was maximal after 6 weeks and lower after 12 weeks. Treatment with aminoguanidine (1 g/l drinking water) decreased O2*- generation after 6 weeks but not after 12 weeks. NO production by both unstimulated and opsonized zymosan-stimulated granulocytes was elevated in diabetic rats to a comparable extent after 6 and 12 weeks. AG attenuated this increased NO production. These results point to the beneficial effect of AG on oxidative stress in experimental diabetes and suggest an antioxidant effect of AG.

Myoinositol may be a factor in uremic immune deficiency.

In 10 chronic uremic patients on regular hemodialysis treatment and 10 healthy subjects in vitro PHA-induced peripheral blood mononuclear cell (PBMNC) and T-cell enriched lymphocyte proliferative responses were found to be impaired in the presence of myoinositol in the concentration generally observed in the blood serum of chronic uremic patients on regular hemodialysis treatment (600 mumol/l), while it remained unchanged in the presence of myoinositol in the concentration observed in normal blood serum (30 mumol/l). However, both myoinositol concentrations did not affect PMA-induced PBMNC and T-cell enriched lymphocyte proliferative responses, which suggests that inhibitory effect of the high myoinositol concentration on PHA-induced immune cell proliferation is cell membrane-related. In addition, myoinositol (600 mumol/l) significantly depressed CD3, CD4 and HLA-DR antigen expression on PHA-activated PBMNC surface in chronic uremic patients and healthy subjects, while CD8 antigen expression remained unaffected. The results seem to indicate that myoinositol, in the concentrations observed in uremic blood serum, may possibly share the responsibility for uremic immune deficiency.

Nitric oxide release in the peripheral blood during hemodialysis.

These studies evaluated the nitric oxide (NO) release in peripheral blood during a four-hour hemodialysis (HD) with single-used cuprophane (CU), polysulfone (PS) and polyacrylonitrile (PAN) membranes in 10 chronic uremic patients. Continuous monitoring of blood NO concentrations was performed with a sterile NO sensor probe inserted vertically into the arterial blood line between the arteriovenous fistula and dialyzer. In the initial period of HD two peaks of blood NO concentrations were observed: the first occurred at the very start of HD and lasted approximately one minute, and the second peaked to a lesser extent at 20 to 26 minutes after the initiation of HD. The extent of NO release was dependent on the type of dialysis membrane used. Areas under curves for blood NO concentrations (in mumol x min) were as follows: CU, 450.8 +/- 163.3; PS, 247.3 +/- 150.6*; PAN, 200.4 +/- 91.0* (*P < 0.05 vs. CU). During the first hour of HD (N = 6) blood NO concentrations were significantly higher at the outlet of CU dialyzer than those found at the inlet. The areas under their curves (in mumol x min) were 169.1 +/- 1.9 and 107.5 +/- 1.6, respectively (P < 0.001). Areas under curves for blood NO concentrations measured for five minutes following a five-minute in vitro incubation of 5 ml heparinized uremic blood samples (N = 10) with dialysis membranes (50 cm2) were as follows (in nmol x min): CU, 2380 +/- 289*; PS, 1293 +/- 45*; PAN, 1117 +/- 37*; control, 502 +/- 56 (*P < 0.05 vs. control). The addition of sodium heparin to uremic blood platelet suspension induced an immediate rise in NO release in a dose-dependent manner, which proved to be a hyperbolic relationship. During HD with CU (N = 6), PS (N = 6) and PAN (N = 6) membranes blood plasma cGMP concentrations significantly increased, particularly at 20 and 60 minutes of the procedure. No significant differences in blood plasma cGMP levels were found between individual dialysis membranes, and no significant correlations were observed between blood plasma cGMP levels and blood NO concentrations. The results indicate that during HD NO is released in the peripheral blood due to blood-membrane and heparin-blood platelet interactions. The extent of intradialytic NO release is dependent on the type of dialysis membrane used (CU > PS approximately PAN).

Changes in red blood cell membrane structure in patients with chronic renal failure.

The properties of red blood cell membranes in patients with chronic renal failure were investigated using electron paramagnetic resonance spectroscopy. Using spin traps, 5,5-dimethylpirroline-1 oxide and N-tert-butyl-alpha-phenylnitrone, we found generation of hydroxyl radicals in the blood of patients with chronic renal failure after 20 min of regular hemodialysis. The physical state of membrane proteins and membrane osmotic fragility and reductive properties of red blood cells were studied. The increase in the relative correlation time of 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidine-1 oxyl indicates the immobilization of membrane protein molecules in erythrocytes of chronic renal failure patients. The decrease in membrane protein mobility was observed in whole blood incubated with tert-butylhydroperoxide, regardless of the presence of iron. We found that the addition of ferrous ions did not aggravate profound changes in membrane proteins induced with tert-butylhydroperoxide. We also demonstrated higher osmotic fragility of erythrocytes in the patients with renal failure as compared to normal subjects. These alterations in membrane structure of red blood cells in hemodialysed patients suggest that hydroxyl radicals generated during hemodialysis can play an important role in the oxidative mechanism of erythrocyte damage.

[Function of the left heart atrium during hemodialysis]. / Czynnosc lewego przesionka serca podczas hemodializy.

In 23 chronic uremic patients effect of four-hour hemodialysis on function the left atrium of the heart was investigated. The reference group consisted of 17 healthy subjects. The function was evaluated by cross-sectional Doppler echocardiography. Before hemodialysis maximal (LAmax) and minimal (LAmin) left atrial dimensions and left atrial dimension obtained in M-mode of long axis in parasternal projection (LAa), pre-ejection period (PEPlp), ejection time (ETlp), PEPlo/ETlp ratio and left atrial fiber shortening fraction (FS%lp) were significantly higher in chronic uremic patients than those found in healthy subjects. Four-hour hemodialysis induced decreases in these indices, but only a lowering of LAa, PEPlp/ETlp ratio was statistically significant in comparison with pre-dialysis period. No correlation was found between changes of the investigated indices of the left atrial function and body weight loss during hemodialysis.

The effect of coronary angioplasty on superoxide anion generation and lipid peroxidation. Propriety of pharmacological intervention.

In patients with unstable angina pectoris, subjected (n = 20) or not subjected (n = 12) to percutaneous transluminal coronary angioplasty (PTCA), baseline superoxide anion (O.2-) generation by neutrophils in the coronary sinus blood was significantly higher than that found in the basilic vein blood of control healthy subjects (n = 12). During reperfusion following effective PTCA, neutrophil counts in the coronary sinus blood tended to decrease, an effect accompanied by a significant decrease in the neutrophil O.2- generation and enhancement of blood plasma lipid peroxidation as reflected by increased malonyldialdehyde concentrations.

Myoinositol incorporation into lymphocytes of chronic renal failure patients is impaired.

Incorporation of myo-[2-3H]-inositol into peripheral blood mononuclear cells (PBMNC) and T-cell enriched lymphocytes was evaluated in in-vitro experiments in chronic renal failure (CRF) patients and healthy subjects. Incorporation of myo-[2-3H]-inositol into the cells of CRF patients on conservative and haemodialysis treatment was found to be impaired in comparison with that observed in normal cells. Following PHA stimulation of the cells of CRF patients myo-[2-3H]-inositol incorporation decreased even further, while it increased in normal cells. Five-hour haemodialysis session significantly depressed myoinositol incorporation into PBMNC, while its incorporation into T-cell enriched lymphocytes remained unaffected. Myoinositol incorporation into PBMNC and T-cell enriched lymphocytes was inhibited by prostaglandins and leukotrienes and was inversely related to the extent of pertussis toxinsensitive G protein activation. Reduced myoinositol incorporation into uraemic PHA-stimulated PBMNC may depend at least in part on their enhanced PGE2 and LTB4 release accompanied by increased intracellular cAMP production. In CRF impaired myoinositol incorporation into immune cells may prove the disarrangement in the early events of transmembrane signal transduction, which may share the responsibility for the cell-mediated immune defect in these patients.