Trace elements in end-stage renal disease. 1. Methodological aspects and the influence of water treatment and dialysis equipment.

For human beings trace elements are essential nutrients with a gamut of functions. They are for instance indispensable components of many enzymes, so they have some regulatory functions and they may affect immune reactions and free radical generation. Altered blood levels of different trace elements have been described in patients with advanced renal failure and especially in those treated by different kinds of renal replacement therapy. Altered renal function may result in impaired renal excretion of trace elements and their accumulation or depletion in the body. The dialysate concentrate and water used for preparing the dialysate may be an important source of the accumulation or depletion of trace elements in dialyzed patients. The gain or loss of trace elements during dialysis depends on the gradient between the ultrafiltrable fraction of a particular element in serum and its concentration in the dialysis fluid, and also on the type and permeability of the dialysis membrane. There are some methodological problems concerning the handling and storing of blood samples and measurement techniques leading to the rather inconsistent results of different studies concerning trace elements in renal disease. Geographical variations and environmental contamination of soil and water and different dietary habits may significantly influence trace elements in these patients. The abnormalities of trace elements are primarily the result of uremia, and they may be further modified and sometimes greatly exacerbated by the dialysis procedure.

Trace elements in end-stage renal disease. 2. Clinical implication of trace elements.

For human beings trace elements are essential nutrients with a gamut of functions. They are for instance indispensable components of many enzymes, so they have some regulatory functions and they may affect immune reactions and free radical generation. Abnormalities of trace elements are primarily the result of uremia, and they may be further modified and sometimes greatly exacerbated by the dialysis procedure. The role of trace elements in hemodialysis (HD) patients has not yet been fully characterized. To prevent some complications in chronic HD patients, it is very important to regulate the levels of trace elements by adequate water treatment. Reverse osmosis is able to prevent the accumulation of the majority of trace elements in the patients. Zinc supplementation may be recommended for patients with proven zinc deficiency, but for all chronic renal failure patients it is questionable. Selenium deficiency is to be suspected in dialyzed patients and selenium supplementation may be beneficial (increasing glutathione peroxidase activity, cardioprotective effect, immunostimulatory properties) for chronic renal failure patients. Supplementation with a trace element may be indicated when its depletion was unequivocally documented and when there is evidence of the positive effects of this element on the quality of life of the dialyzed patients.

Chromium levels in patients with internal diseases.

Chromium (Cr), an essential element, mainly affects saccharide (potentiated insulin action via interaction with insulin receptor on the cell surface) and lipid metabolism (inhibition of hydroxymethylglutaryl-CoA reductase with a hypolipidemic effect). The aim of the study was to describe Cr serum levels in different diseases (malignant, metabolic, renal) using an advanced analytical technique with correlation to other biochemical parameters. The concentration was measured using atomic absorption spectrometry with electrothermal atomization. The Cr levels were increased in hemodialysis patients-HD (3.67 +/- 0.35 micrograms/L) compared to controls-C (0.40 +/- 0.12 microgram/L), in significantly changed in diabetic patients-DM (0.29 +/- 0.08 microgram/L) and patients with lymphoproliferative disease-LP (0.24 +/- 0.07 microgram/L), and decreased in hyperlipidemic patients-HL (0.15 +/- 0.03 microgram/L). There were no differences in Cr concentration between DM treated by diet or peroral antidiabetic drugs; likewise hypolipidemic drugs in HL did not change the Cr concentration. The biochemical parameters-total protein, transferrin in LP group, glucose in DM group, total cholesterol, triacylglycerols, LDL-cholesterol, apolipoprotein B and A-I did not correlate with serum Cr concentration. However, the HDL-cholesterol concentration marginally significantly (p < 0.07) correlated with it. The role of Cr in humans has not yet been fully characterized. To prevent some complications in patients, it may be important to monitor the Cr levels. Chromium supplementation may be indicated in some diseases with no controversy concerning the importance of decreased serum and/or tissue levels and documented positive effects of Cr supplementation on the quality of life (e.g. hyperlipidemia).

ICRF-187 (dexrazoxan) protects from adriamycin-induced nephrotic syndrome in rats.

BACKGROUND: Reactive oxygen species produced during metabolism of adriamycin are purported to play an important role in the pathogenesis of experimental adriamycin nephropathy in rats. ICRF-187 (dexrazoxan, Cardioxan), an iron chelator, has been shown to inhibit adriamycin-induced formation of hydroxyl radical and to decrease adriamycin cardiotoxicity in oncological patients. The aim of our study was to assess the putative protective role of ICRF-187 in adriamycin nephropathy by evaluating the possible participation of free radicals in its pathogenesis. METHODS: We examined five experimental groups. Group A, received a single dose of adriamycin (5 mg/kg bw i.v.), group CA was given a single dose of ICRF-187 (100 mg/kg bw i.v.) before adriamycin administration, group CCA received a single dose of ICRF-187 (100 mg/kg bw i.v.) before adriamycin administration followed by three weekly intraperitoneal injections (100 mg/kg bw) ICRF-187. Group CC received one dose of ICRF-187 (100 mg/kg bw i.v.) followed by three weekly intraperitoneal injections of ICRF-187, and group N served as control receiving saline. Common biochemical parameters, malondialdehyde (MDA) and antioxidant enzymes (glutathione peroxidase--GPx and superoxide dismutase--SOD) in blood and kidney homogenates were measure and histology of the kidney was studied after the rats were sacrificed. RESULTS: Full-blown nephrotic syndrome developed after 3 weeks only in A rats. Nephrotic syndrome was completely prevented in all ICRF-187 treated rats (CA, CCA). Proteinuria was significantly increased in A rats (108.2 + 48.4 mg/l of glomerular filtrate) compared with CA (12.4 + 6.8 mg/l, P < 0.0001) and with N (6.1 + 3.5 mg/l, P < 0.0001). Total MDA in erythrocytes was significantly increased only in A rats (1.7 + 0.3 micromol/l) and was completely normalized by ICRF-187 in CA (1.1 + 0.2 micromol/l, P < 0.001). Total TBARS and MDA in kidney homogenates were significantly elevated in groups with repeated administration of ICRF-187 (CC and CCA rats) compared to N, CA, A groups. Activity of GPx and SOD in kidney homogenate and in erythrocytes was not significantly increased by ICRF-187 in adriamycin treated rats. Histologic changes in A rats resembled minimal change nephropathy with fusion of foot processes and hyaline casts in tubules. There was only minimal mesangial proliferation and perivascular mast cell infiltrates in all groups of ICRF-187-treated rats. CONCLUSIONS: We conclude that ICRF-187, probably by chelation iron, completely protected rats from adriamycin-induced nephrotic syndrome. It supports the role of iron-mediated reactive oxygen species in the development of this type of glomerular injury. However, repeated administration of ICRF-187 alone is able to increase parameters of oxidative stress in the kidney.

Retinol and alpha-tocopherol in hemodialysis patients.

The biological effects of reactive oxygen species and other radicals controlled by antioxidant mechanisms are modified by various enzymes and other substrates. Antioxidant substrates are divided into those with lipophilic and hydrophilic groups. Retinol and tocopherol are the main representations of lipophilic antioxidants. The aim of the present study was to describe the changes of retinol and alpha-tocopherol which occurred in hemodialysis (HD) patients in respect to the influence of antioxidant systems. The experimental group consisted of 14 patients on regular HD treatment. The control group consisted of 14 healthy blood donors. HPLC was used to measure retinol and alpha-tocopherol in serum. We found that the retinol concentration was significantly higher in HD patients compared to controls (2.35 +/- 0.95 versus 0.90 +/- 0.23 mg/L, p < 0.0001). The concentration of alpha-tocopherol in serum was not different in both study groups (7.32 +/- 3.01 versus. 8.94 +/- 3.57 mg/L). A review of the MEDLINE database since 1985 found a few references concerning these important antioxidant vitamins in HD patients and these contained contrasting results. It has been suggested that some of the complications related to HD including cardiovascular complications, anemia and atherosclerosis may be due to ineffective antioxidant systems and/or to increased free oxygen radical production. The question about supplementation of antioxidants in HD patients is open although there are some positive data regarding the use of moderate and safe selenium supplementation in HD patients. HD patients treated by erythropoietin had increased plasma concentration of retinol and normal level of alpha-tocopherol compared to healthy group. However, this positive finding did not affect lipid peroxidation, which is increased in HD patients and leads to some complications during HD treatment.

Trace elements in hemodialysis and continuous ambulatory peritoneal dialysis patients.

Alterations in blood and tissue concentrations of trace elements in patients with chronic renal failure have been extensively investigated. Selenium, zinc and copper are elements which play an important role in biological systems as components of proteins, enzymes and antioxidants. The concentrations of selenium, zinc and copper were determined in the plasma, erythrocytes and whole blood of patients on regular hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) treatment using the method of inductively coupled plasma mass spectrometry (ICP-MS). Analysis of isotopes 77Se, 66Zn and 65Cu was performed. Methodology presents the major limitation to valid studies on trace element levels in biological materials. One of the widely used contemporary techniques is ICP-MS. It is the most sensitive one and has a high dynamic range. The selenium concentration in the studied compartments (plasma 46.1 +/- 3.0 vs. 78.0 +/- 3.4 microgram/l, p < 0.001; erythrocytes 90.4 +/- 6.5 vs. 134.2 +/- 7.6 microgram/l, p < 0.01; whole blood 67.3 +/- 3.1 vs. 106.4 +/- 3.4 microgram/l, p < 0.001) was significantly lower in HD patients compared to healthy controls. The same result was observed in plasma (63.2 +/- 5.8 vs. 78.0 +/- 3.4 microgram/l, p < 0.05) and whole blood (82.7 +/- 7.4 vs. 106.4 +/- 3.4 microgram/l, p < 0.01) from CAPD patients, but the selenium level of erythrocytes in CAPD patients was the same as in the control group (126.0 +/- 8.8 vs. 134. 2 +/- 7.6 microgram/l). The cooper content of erythrocytes was lower in HD patients than in controls (0.55 +/- 0.02 vs. 0.66 +/- 0.01 mg/l, p < 0.01) and CAPD groups (0.55 +/- 0.02 vs. 0.68 +/- 0.02 mg/l, p < 0.001). There were no differences in copper content in plasma (HD 1. 02 +/- 0.06; CAPD 1.11 +/- 0.09; controls 1.02 +/- 0.05 mg/l) and whole blood (HD 0.87 +/- 0.04; CAPD 0.90 +/- 0.05; controls 0.85 +/- 0.02 mg/l) in HD and CAPD patients and healthy controls. The zinc concentration was increased in the whole blood of CAPD patients (6. 68 +/- 0.36 vs. 5.52 +/- 0.11 mg/l, p < 0.001) and erythrocytes of HD (12.30 +/- 0.23 vs. 10.11 +/- 0.42 mg/l, p < 0.001), and CAPD groups (13.71 +/- 0.56 vs. 10.11 +/- 0.42 mg/l, p < 0.001) compared to controls. However, the plasma zinc concentration was lower in HD patients compared to blood donors (0.69 +/- 0.03 vs. 0.92 +/- 0.03 mg/l, p < 0.001) and CAPD patients (0.69 +/- 0.03 vs. 0.95 +/- 0.04 mg/l, p < 0.001). We did not find a significant increase in trace elements in whole blood after HD. These results suggest differences between plasma, erythrocytes and whole blood concentrations of the studied trace elements. The levels of trace elements are altered by HD and CAPD. A modern precise method with high accuracy, ICP-MS, which was used in our study, eliminated analytical errors and possible interferences.

[Dialysis therapy in the Czech Republic in 1995]. / Dialyzacní lécba v Ceské republice v roce 1995.

1. The number of haemodialyzation centres has more than doubled in the course of five years which increased the dialyzation capacity and at present no patient in the Czech Republic should be denied dialyzation treatment on technical or financial grounds. 2. The number of newly enlisted patients "from the street" remains unfavourable, one third, who are not prepared for this financially pretentious treatment and who have many complications. General practitioners and diabetologists should refer in time patients with chronic renal failure (with a creatinine level above 300 mumol/l) to nephrological--predialyzation clinics. 3. The dialyzed population is aging and in the dialyzation programme polymorbid patients, specially diabetics are increasing in numbers. Therefore the mortality has a rising trend and this will persist. The most frequent cause of death are, similarly as in other countries, cardiovascular complications. 4. The development of another method for the treatment of renal failure is promising--peritoneal dialysis which is used in treatment of almost 5% patients. 5. The number of patients treated by HD per 1 million population is relatively high but only because other therapeutic methods applied in renal failure are not used in a sufficient number of patients. This results in a lower rate of patients treated by RRT methods (HD+PD+TPL)/1 million population, as compared with advanced European countries.

[Use of multivariate analysis in medical chemistry]. / Vyuzití vícerozmerné analýzy rozptylu v lékarské chemii.

Alternations in trace elements concentrations are intensively studied because of their possible role in pathogenesis and progress of diseases. Three groups of patients were investigated: haemodialysis patients (HD) (n = 17), continual ambulatory peritoneal dialysis patients (CAPD) (n = 11), and control group of blood donors (n = 12). They were analyzed for Se, Zn and Cu concentration in plasma and erythrocytes by inductively--coupled plasma mass spectroscopy. Distribution of analyzed elements between these blood compartments was found different in all groups of studied patients. Erythrocytes were enriched by Se (twofold higher concentration compared to plasma) and by Zn (10-20 fold higher concentrations compared to plasma). On the other hand, human plasma was enriched by Cu (approximately twofold higher concentration then in erythrocytes). Results of analyses were processed by multivariate analysis of variance (MANOVA). When only results of plasma analysis were involved into MANOVA, differences between HD patients and other two groups were found whereas CAPD and control group were not distinguished each other. However, these two groups were mutually differenced when MANOVA comprised all trace elements concentrations: both plasma and erythrocytes. Methods of multivariate statistic are able to study not only the individual variables but even their mutual relations and their medical applications are very useful.

The influence of cyclosporin on lipid peroxidation and superoxide dismutase in adriamycin nephropathy in rats.

Cyclosporin A (CsA) was shown to reduce proteinuria in nephrotic syndrome, but its potential to increase lipid peroxidation may play a role in cyclosporin nephrotoxicity. The influence of cyclosporin treatment on the lipid peroxidation (assessed as malondialdehyde (MDA) in plasma and kidney homogenates using HPLC and reaction with thiobarbituric acid) and the activity of superoxide dismutase (SOD) in erythrocytes was studied in rats with nephrotic syndrome induced by single intravenous injection of adriamycin. Rats with nephrotic syndrome treated from the beginning with cyclosporin had lower proteinuria than untreated nephrotic rats. Free MDA in blood and kidney homogenates was significantly elevated in untreated nephrotic rats in comparison with controls. Activity of SOD in erythrocytes was significantly elevated in nephrotic rats treated with cyclosporin (113.40 +/- 34.31 mU/10(6) erythrocytes) in comparison with the control group (55.63 +/- 9.90 mU/10(6) erythrocytes, p < 0.001), rats treated with cyclosporin (65.7 +/- 17.49 mU/10(6) erythrocytes, p < 0.01) and untreated nephrotic rats (65.07 +/- 17.49 mU/10(6) erythrocytes, p < 0.001). In conclusion, cyclosporin reduced proteinuria in rats with mild adriamycin nephropathy (similar to human minimal change disease). Cyclosporin also partially counteracted adriamycin-induced lipid peroxidation probably due to the stimulation of antioxidant enzyme SOD. The possible contribution of decreased lipid peroxidation to the antiproteinuric effect of cyclosporin deserves further study.

The influence of pefloxacine on experimental adriamycin-induced nephrotic syndrome in rats.

Initial reports on antiproteinuric effect of pefloxacine in small groups of patients with minimal-change nephropathy (MCN) and focal and segmental glomerulosclerosis (FSGS) have not been confirmed in other papers. To assess its antiproteinuric effect in experimental animals we administered pefloxacine to rats with adriamycin nephropathy showing morphological changes resembling human minimal-change disease or focal segmental glomerulosclerosis, and clinically with full-blown nephrotic syndrome. Pefloxacine treatment was at least partially effective in preventing further increase of proteinuria in rats with adriamycin nephropathy. The mechanism of this effect remains unclear and deserves further studies concentrating on the glomerular cytokine network and glomerular production of reactive oxygen species.

Lipid peroxidation and antioxidant enzymes in CAPD patients.

The mechanisms of free-radical injury include reactions with proteins, nucleic acids, and polysaccharides; and covalent binding to membrane components and initiation of lipid peroxidation. Cells have developed antioxidant defense to prevent free-radical injury including superoxide dismutase (SOD) and glutathione peroxidase (GPx). Significantly higher concentrations of total malondialdehyde (MDA) in plasma (1.22 +/- 0.42 vs. 0.64 +/- 0.22 micromol/L, p < 0.0001) as well as erythrocytes (2.56 +/- 1.28 vs. 1.03 +/- 0.44 micromol/L, p < 0.0001) of the CAPD patients were found when compared to the control group. The free MDA in plasma and the erythrocytes do not differ significantly in continuous ambulatory peritoneal dialysis (CAPD) patients and the control group. A significantly lower activity of GPx in erythrocytes of CAPD patients (17.85 +/- 2.63 U/g Hb vs. 23.26 +/- 3.61 U/g Hb, p < 0.0001) was found when compared to the control group, but the SOD activity in erythrocytes is not different (2272.36 +/- 579.92 U/g Hb vs. 2347.13 +/- 502.51 U/g Hg, NS). Our results show an increase of total MDA in erythrocytes and plasma. MDA is the product of lipid peroxidation with decreasing activity of GPx, which is capable of detoxifying peroxides. The activity of SOD did not change in CAPD patients. These results propose a possible role of free radicals with reduced antioxidant activity of GPx in CAPD patients and indicate that they could play some role in other pathological conditions such as atherogenesis and hemolysis.

[Lipid peroxidation and activity of antioxidative enzymes in patients with multiple myeloma]. / Lipoperoxidace a aktivita antioxidacních enzymu u pacientu s mnohocetným myelomem.

BACKGROUNDS: Reactive oxygen species and other free radicals are known to be the mediators of phenotypic and genotypic changes that lead from mutation to neoplasia. The imbalance in tumor cell antioxidant defense mechanism can influence also the sensitivity to cytoreductive therapy. In erythrocytes it can results to hemolysis which is one of pathogenetic mechanisms of anemia in cancer patients. METHODS AND RESULTS: We investigated the parameters of lipid peroxidation (malondialdehyde-MDA) and antioxidant enzymes here represented by superoxide dismutase (SOD) and glutathione peroxidase (GPx) in multiple myeloma. Nine patients of various clinical stage and activity of disease were studied. A significant higher concentration of total MDA in plasma (1.20 +/- 0.24 mumol/l v.s. 0.64 +/- 0.22 mumol/l, p < 0.0001) as well as in erythrocytes (2.72 +/- 0.81 mumol/l v.s. 1.03 +/- 0.44 mumol/l, p < 0.0001) was found comparing to the control group. The levels of free MDA in plasma (0.31 +/- 0.09 mumol/l v.s. 0.49 +/- 0.17 mumol/l, p < 0.05) and in erythrocytes (0.29 +/- 0.20 mumol/l v.s. 0.59 +/- 0.22 mumol/l, p < 0.001) were decreased in myeloma patients. A significantly lower activity of GPx (19.17 +/- 4.07 U/g v.s. 23.26 +/- 3.61 U/g Hb, p < 0.05) and SOD (1882.46 +/- 181.73 U/g v.s. 2347.13 +/- 502.51 U/g Hb, p < 0.05) in erythrocytes were found. CONCLUSIONS: We didn't observe evident relationship between the concentration of MDA or activities of SOD and GPx and either the stage of disease or level and type of paraprotein. We can conclude, that higher concentration of total MDA as a parameter of lipid peroxidation, is significantly increased in patients with multiple myeloma. It could be consequence of impaired antioxidant defence. These results propose possible role of free radicals with reduced antioxidant activity of SOD and GPx in multiple myeloma. As we can consider the role of free radicals in pathogenesis of malignant proliferation, prognostic value and the change during the course of therapy should by studied.

Antioxidant enzymes--superoxide dismutase and glutathione peroxidase--in haemodialyzed patients.

The biological effect of oxygen-reactive species controlled by antioxidant mechanisms are exerted on the basis of antioxidant enzymes and substrates. In this study, the activities of antioxidant enzymes-superoxide dismutase (SOD) and glutathione peroxidase (GPx)-were determined in the erythrocytes of patients on regular haemodialysis treatment. The SOD activity was significantly lower (1,810.38 +/- 609.85 vs. 2,347.13 +/- 502.51 U/g haemoglobin, p < 0.05, or 70.71 +/- 11.50 vs. 100.13 +/- 24.28 mU/10(6) erythrocytes, p < 0.0001), as was the GPx activity (18.80 +/- 4.22 vs. 23.26 +/- 3.61 U/g haemoglobin, p < 0.01), when compared with the control group. A positive correlation between GPx activity and number of haemodialysis sessions was found (p = 0.0038), but no correlation between SOD activity and number of HD sessions. An inpaired antioxidant enzyme defence system, here represented by SOD and GPx levels, can potentiate injury caused by free radicals in haemodialysis patients.

[Dialysis therapy in the Czech Republic in 1994]. / Dialyzacní lécba v Ceské republice v roce 1994.

1. In 1994 were 81 haemodialysis centers in the Czech Republic (including 12 private ones, i.e. 7.7 p.m.p.). 2. The capacity of dialysis centres enabled an outstanding number of new patients to be accepted--120 p.m.p. (the European average was half that number). Majority of the new patients were from higher age groups and diabetics. The number of patients, who were not followed prior to renal replacement therapy, still remains one third of the newly accepted ones. 3. In 1994 there were 3592 patients on dialysis treatment--342 p.m.p. (the maximum number so far), but by December 31st 1994 there were 2691 patients--256 p.m.p. surviving on dialysis treatment. We have achieved higher number dialysed patients p.m.p. than any other country of the former Eastern bloc, including the GDR. Mortality was 14%. 4. Hepatitis B as well as C remains a major problem, although there has been a slight decline of HBsAg positive patients. 5. The technical facilities for dialysis treatment are not optimal. 6. A favourable trend continued in the development of peritoneal dialysis programme.

[The role of oxygen radicals in the pathogenesis of glomerulonephritis]. / Uloha kyslíkových radikálu v patogenezi glomerulonefritid.

In the pathogenesis of glomerulonephritis, acute renal failure, pyelonephritis and other diseases of the kidneys oxygen radicals are involved. Some types of glomerulonephritis are characterized by infiltration of the glomeruli by neutrophils and monocytes which can form oxygen radicals (superoxide, hydrogen peroxide). The increased amount of cAMP in glomeruli can be due to oxygen radicals. Cyclic nucleotides modulate the inflammatory or immune response in glomerular disease and play a part in the action of local mediators of the inflammation. Oxygen radicals act as second messenger for the activation of cytokines via NF-kappaB transcription factor, they stimulate the formation of TNF-alpha, IL-1, IL-6 and influence the expression of monocyte-specific cytokines (CSF-1 and MCP-1). Radicals formed by the system myeloperoxidase--hydrogen peroxide--halogen derivatives activate proteolytic enzymes (proteinases) which break down collagen and other components of the extracellular matrix present in the basal membrane of glomeruli and in the mesangium. Oxygen radicals and proteinases can cause and amplify glomerular damage. Glucocorticoid administration leads to an increased activity of endogenous antioxidant enzymes in the glomerulus and reduced the of lipid peroxidation.

[The effect of pefloxacin on nephrotic syndrome in experimental adriamycin nephropathy]. / Vliv pefloxacinu na nefrotický syndrom u experimentální adriamycinové nefropatie.

BACKGROUND: Antiproteinuric effect of pefloxacine was demonstrated in a small group of patients with minimal change nephropathy (MCN) and focal and segmental glomerulosclerosis (FSGS). This finding was not, however, confirmed by other papers. Adriamycine nephropathy is an experimental model of nephrotic syndrome with morphological changes resembling MCN and/or FSGS in patients. METHODS AND RESULTS: Nephrotic syndrome was induced in rats by the i.v. administration of adriamycine. One part of nephrotic animals was treated from the beginning of the 4th week by daily intraperitoneal application of pefloxacine. Administration of adriamycine led in experimental animals after 3 weeks to the development of full-blown nephrotic syndrome with further progression of proteinuria in the next 3 weeks (from 1.4 +/- 1.25 to 2.23 +/- 1.89 g of protein/mmol of urinary creatinine, p < 0.05). Proteinuria did not change in nephrotic rats treated by pefloxacine (from 1.04 +/- 0.97 to 1.26 +/- 1.11 g of protein/mmol of urinary creatinine, p = n.s.). The difference in proteinuria between both groups was also significant (0.83 +/- 0.73 vs. 0.23 +/- 0.67 g of protein/mmol of urinary creatinine, p < 0.05). CONCLUSIONS: Pefloxacine was antiproteinuric in experimental adriamycine nephropathy. The mechanism of this effect remains unclear and deserves further studies concentrating on glomerular cytokine network and glomerular production of reactive oxygen species.

Endothelin in patients with chronic renal failure.

Hypertension, anemia, and arteriovenous shunts represent very important pathogenic factors in the occurrence of cardiovascular morbidity and mortality in patients with chronic renal failure. It can be expected that endothelin (ET), the most potent vasoconstrictor known at present, can react in a significant way to the hemodynamic changes caused by the construction of a vascular shunt or anemia. In 14 patients the plasma ET concentration was examined before and 24 and 7 days after the construction of arteriovenous fistula. In 27 patients undergoing chronic hemodialysis treatment, ET was examined before the erythropoietin (EPO) therapy and after 2 months of EPO therapy, when partial correction of anemia had been achieved. The construction of arteriovenous fistula by itself had no significant influence on the plasma ET concentration. Subcutaneous application of EPO in doses that led to gradual correction of anemia was not accompanied by the rise of plasma ET. The average plasma concentration of ET was significantly higher in hemodialyzed patients, when compared to healthy controls as well as to patients with chronic renal failure before hemodialysis treatment was started.

[Endothelin in patients with chronic kidney failure]. / Endotelin u nemocných s chronickým selháním ledvin.

BACKGROUND: Hypertension, anaemia and arteriovenous shunts represent very important pathogenetic factors in the occurrence of cardiovascular morbidity and mortality in patients with chronic renal failure. It can be expected that endothelin (ET), the most potent vasoconstrictor known at present, can react in a significant way to the haemodynamic changes, caused by the construction of a vascular shunt or anaemia. METHODS AND RESULTS: In 14 patients (7 men and 7 women, mean age 47 years, ranging from 19 to 70 years) the plasma ET concentration was examined before, 24 hours and 7 days after the construction of arteriovenous fistula. In 27 patients (19 men and 8 women, mean age 44 years ranging from 25 to 77 years), undergoing chronic haemodialysis treatment, ET was examined before the erythropoietin (EPO) therapy and after 2 months of EPO therapy, when partial correction of anaemia has been achieved (p < 0.01). CONCLUSIONS: The construction of arteriovenous fistula by itself had no significant influence on the plasma ET concentration. Subcutaneous application of EPO in such doses, which led to gradual correction of anaemia, was not accompanied by the rise of plasma ET. The average plasma concentration of ET was significantly higher in haemodialyzed patients, when compared to healthy controls as well as to patients with chronic renal failure before haemodialysis treatment was started.

[Successful completion of pregnancy in a dialyzed patient]. / Uspesne ukoncené tehotenství u dialyzované pacientky.

The authors describe the first case of a successful pregnancy in the Czech Republic in a patient treated by continuous ambulatory peritoneal dialysis. The 22-year-old patient became pregnant ten months after the onset of treatment by peritoneal dialysis. During pregnancy deterioration of arterial hypertension occurred, deterioration of anaemia and from the 29th week onwards cholestasis gravidarum developed. The development of the foetus was within normal limits. Because of suspected preeclampsia the pregnancy was terminated during the 35th week by Caesarean section. The patient was delivered of a healthy eutrophic boy without any congenital abnormalities.

[Free radicals in the pathogenesis of selected diseases]. / Volné radikály v patogenezi vybraných onemocnení.

Free radicals are chemical substances which contain one or more unpaired electrons, which is the cause of their high reactivity with a series of biologically important substances such as fatty acids, DNA, RNA, amino acids. The source of radicals are immunological reactions and reactions in the endoplasmatic reticulum during detoxication of xenobiotics. Free radicals can act on the organism by a number of reactions, the most frequent on being lipid peroxidation when important toxic products are formed such as 4-hydroxy 2,3 trans-nonenal (4-HNE) and malondialdehyde. Direct assessment of free radicals due to their short life span is difficult in clinical practice. The majority of measurements is based on the assessment of substances which are formed by the reaction of free radicals in the organism. The most frequent method is assessment by means of thiobarbituric acid. Oxidative stress (the reaction produced by the action of free radicals) of tissues and cells is caused by the increased formation of free radicals and/or reduced capacity of antioxidant systems. Free radicals are involved in the process of ageing, cancerogenesis, inflammatory and degenerative diseases, atherogenesis, and play a part in the ischaemic and toxic damage of the organism. During evolution antioxidant defence mechanisms developed which under physiological conditions are sufficient to inactivate free radicals. Antioxidant systems can be divided into two groups--antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase etc) and antioxidant substrates (tocopherols, carotenoids, ascorbic acid, glutathione, transferrin, ceruloplasmin etc).