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Biomedical subjects

J Racek

Publications and source records attributed to J Racek.

At least 37 records · Page 2Linked to original sources

[Free radicals and antioxidants in cerebrospinal fluid in central nervous system diseases].

Free radicals and antioxidants may play a role in the etiology and pathogenesis of some central nervous diseases. The brain tissue is relatively insufficiently protected by antioxidants against the free radical induced damage. The brain situation may be reflected by the cerebrospinal fluid examination, which has not enough attention. It seems, that from this point of view subarachnoical hemorrhagy, meningitis, hydrocephalus, Alzheimer's, Parkinson's and Huntington's diseases, multiple sclerosis and probably schizophrenia should receive a special attention.

Antioxidants↗

[Less common risk factors for atherogenesis--homocysteine, lipoprotein (a) and C-reactive protein].

Atherosclerosis and its complications belong to the most frequent causes of morbidity and mortality in the developed countries. Far from all cases of early atherosclerosis can be explained by presence of "classical" risk factors (hypertension, hypercholesterolemia, and namely by oxidised forms of lipoproteins of low density, by smoking or due to not fully compensated diabetes mellitus). Our review brings information of another three serious risk factors--homocysteine, lipoprotein (a), and highly sensitive C-reactive protein. Metabolic relations among them are given as well as results of comparatively independent clinical studies and possibilities to influence these risk factors. Though they are comparatively independent, one feature connects them--they participate significantly on the development of endothelial dysfunction, which is supposed to be the initial stadium of atherogenesis.

Arteriosclerosis↗

Hyperinsulinemia and oxidative stress.

The aim of the study was to compare the effect of short-term hyperglycemia and short-term hyperinsulinemia on parameters of oxidative stress in Wistar rats. Twenty male rats (aged 3 months, average weight 325 g) were tested by hyperinsulinemic clamp (100 IU/l) at two different glycemia levels (6 and 12 mmol/l). Further 20 rats were used as a control group infused with normal saline (instead of insulin) and 30 % glucose simultaneously. Measured parameters of oxidative stress were malondialdehyd (MDA), reduced glutathion (GSH) and total antioxidant capacity (AOC). AOC remained unchanged during hyperglycemia and hyperinsulinemia. Malondialdehyde (as a marker of lipid peroxidation) decreased significantly (p<0.05) during the euglycemic hyperinsulinemic clamp, and increased significantly during isolated hyperglycemia without hyperinsulinemia. Reduced glutathion decreased significantly (p<0.05) during hyperglycemia without hyperinsulinemia. These results suggest that the short-term exogenous hyperinsulinemia reduced the production of reactive oxygen species (ROS) during hyperglycemia in an animal model compared with the control group.

Analysis of Variance↗

[Initial experience with transplantation of a kidney from a non-beating heart donor (NHBD)].

The authors present their initial experience with transplantations of the kidneys from a donor with a non-beating heart (NHBD). This programme was developed because of the permanently declining number of cadaverous kidney donors with a beating heart. Since January 2002 the authors collected a total of three kidneys from NHBD 3 kidneys of which were used for transplantation. The first two started to function immediately, the third one restored its function three weeks after transplantation. The viability and suitability of use of kidneys from NHBD is evaluated with regard to vascular resistance and flow of the perfusion fluid through the kidneys when using a perfusion pump and by means of totalglutathione-S-transferase (tGST) assessed at intervals in the perfusion fluid. The values of the above parameters are limiting between the 6th and 8th hour after the onset of instrumental perfusion of the collected kidneys when the perfusion values should be within the range of 30-50 ml/min/100 g and the vascular resistance should be < 0.7 mmHg and tGST < 100 U/l. For immunosuppression the authors use during the fist days after transplantation basiliximab, rapamycin and corticoids, later in case of satisfactory function of the graft they add cyclosporin A. The initial results of renal transplantation from NHBD are promising and the programme will be developed further.

Cadaver↗

[Paired filtration dialysis and free radicals].

BACKGROUND: Extracorporeal dialysis compensating kidney function represents a risk of elevated production of free radicals (FR). Paired filtration dialysis (PFD) is a hemodialysing method used to compensate kidney function. The aim of our work was to study effects of PFD with two types of hemodiafilters on the activity of free radicals. METHOD AND RESULTS: Group of nine regularly dialysed patients was treated with PFD 1) with demodiafilter SG3, composed of polysulphone high-flux hemodiafilter and hemophane low-flux dialysator, 2) with hemodiafilter SG30, composed of identical hemodiafilter as the above on and of a polysulphone low-flux dialysator. Parameters related to FR were examined before, at 30th minute and at the end of procedure. Plasma concentration of substances reacting with thiobarbiturate acid (TBARS) increased at 30th minute when PFD with SG3 was used (3.24 +/- 0.36 versus 3.48 +/- 0.31, p < 0.01) and at the end of the procedure (3.24 +/- 0.36 versus 3.58 +/- 0.48, p < 0.05). Glutathione values in erythrocytes (GSH) decreased at 30th minute of PFD with SG3 (1.85 +/- 0.27 versus 1.68 +/- 0.20, p < 0.05). Plasma antioxidative capacity decreased at 30th minute and at the end of PFD with equal significance when either type of treatment was used (p < 0.001). Glutathione peroxidase (GSHPx) decreased at 30th minute of PFD with SG30 (35.6 +/- 3.8 versus 32.2 +/- 3.1, p < 0.05). Selenium (Se) in blood decreased at 30th minute (44.9 +/- 5.4 versus 40.4 +/- 5.9, p < 0.05) and at the end of PFD with the same membrane (44.9 +/- 5.4 versus 39.4 +/- 5.2, p < 0.05). CONCLUSIONS: Elevation of TBARS and decrease of GSH show the presence of oxidative stress during the PFD treatment with hemodiafilter SG3. Changes probably result from the contact of blood with the hemophane membrane. The decrease of GSHPx during PFD with hemodiafilter SG30 is probably caused by the loss of Se. From the point of FR production, hemodiafilter SG30 can be considered as more advantageous, from the point of Se loss and decreased activity of GSHPx, hemodiafilter SG3 has better effects.

Adult↗

Effects of a vitamin E-modified dialysis membrane and vitamin C infusion on oxidative stress in hemodialysis patients.

Hemodialysis deteriorates oxidative stress. Vitamin E is an antioxidant whose regeneration is provided for by vitamin C. The authors tested the effects of a vitamin E-modified membrane (E), nonmodified cellulose membrane (O), and vitamin C infusion (500 mg, C) into the arterial blood line during dialysis on parameters of oxidative stress. In a short-term study, 24 patients were subjected to a single dialysis session with E, O, E with C, and O with C protocols. In a long-term study (12 weeks), 20 patients were randomized into groups with C and without C on each dialysis, and both groups had dialysis using O, E, and again O membrane for 4 weeks each. In the short-term study, thiobarbituric acid reacting substances (TBARS) in plasma rose after dialysis (p < 0.02) with O, and no changes were observed in the other 3 protocols. In the long-term study, predialysis TBARS declined when using E both in the groups with C (p < 0.02) and without C (p < 0.05). A switch over to O resulted in TBARS returning to baseline levels. The E membrane prevented an increase in lipid peroxidation during single dialysis, and long-term use of the E membrane also resulted in a decrease in the predialysis lipid peroxidation level. The antioxidant capacity of the E membrane was not enhanced by vitamin C infusion. High doses of vitamin C administered during dialysis using a nonmodified cellulose membrane prevented an increase in lipid peroxidation, most probably due to the enhanced rate of endogenous vitamin E regeneration.

Adult↗

Effect of L-carnitine supplementation in hemodialysis patients.

BACKGROUND/AIM: L-Carnitine is important in beta-oxidation of fatty acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and especially by its loss during dialysis. The aim of our study was to test the influence of carnitine supplementation on plasma lipids, red blood cell count, and metabolism of free radicals. METHODS: Twelve regularly dialyzed patients (average age 55.5 years, average dialysis treatment period 22.5 months) were given 15 mg/kg L-carnitine intravenously three times weekly (after each hemodialysis session) for 6 months. Laboratory markers of oxidative stress, lipid metabolism, and red blood cell count were measured before the supplementation and then controlled during two 3-month intervals. Nine patients were retested 3 months after the supplementation had ended. RESULTS: All supplemented patients showed increased plasma free carnitine in comparison with the pretreatment values (113.3 +/- 11.2 vs. 62.3 +/- 16.7 micromol/l, p < 0.001). The proportion of decreased L-carnitine values after hemodialysis was reduced from 79 to 22%. Plasma total cholesterol (4.66 +/- 0.30 mmol/l after treatment vs. 5.65 +/- 1.53 mmol/l before treatment, p < 0.05) and LDL cholesterol (1.74 +/- 0.86 vs. 2.81 +/- 1.43 mmol/l, p < 0.05) decreased. The albumin concentration significantly increased from 34.8 +/- 7.3 to 46.0 +/-5.4 g/l (p < 0.05). Intraerythrocyte reduced glutathione increased from 1.65 +/- 0.25 to 2.23 +/- 0.16 mmol/l (p < 0.001), and the plasma antioxidant capacity increased from 1.65 +/- 0.09 to 2.06 +/- 0.17 mmol/l (p < 0.001). At the same time, plasma malondialdehyde decreased from 4.18 +/- 0.72 to 3.07 +/- 0.35 micromol/l (p < 0.001). The erythropoietin dose could be reduced from an average value of 5,500 to 3,500 U/week. No significant changes in the above-mentioned parameters were observed in a control group of dialyzed patients without L-carnitine supplementation. CONCLUSION: Regular carnitine supplementation of hemodialysis patients can improve their lipid metabolism, protein nutrition, red blood cell count, and antioxidant status.

Adult↗

[Free radicals in immunology and infectious diseases].

Free radicals contribute significantly in modification of immune processes and inflammatory reactions. They are produced by activated phagocytes which use them for killing microorganisms. Free radicals facilitate production of cytokines, which are important as modifiers of inflammatory reactions. Formation of free radicals is influenced by antioxidants which can thus modify the intensity of inflammatory reaction and immune response. The authors describe in detail the contribution of free radicals in etiology and pathogenesis of autoimmune diseases including rheumatoid arthritis, multiple sclerosis or amyotrophic lateral sclerosis. The role of free radicals and modifying influence of antioxidants in viral, bacterial, parasitic and mycotic diseases is described in the second part of the review. Finally, influence of free radicals and antioxidants on immunity changes in patients with malignant tumours, during aging and physical exercise is discussed.

Aging↗

[Antioxidant effects of melatonin].

Increase in knowledge about reactive oxygen species action mechanisms and oxidative stress effects in living organisms led to intensive seeking for new, more effective substances, which prevent extreme development of oxidative stress or are able to decrease its negative influence, damaging cell structures and many cell functions. These substances are called antioxidants, scavengers, trappers or quenchers. In nineties, melatonin became the centre of the interest in the filed of investigation of antioxidative properties of different chemical substances. This is in living organisms ubiquitous substance with relatively simple chemical structure, good physical properties and wide physiological effects. The main role of endogenous melatonin comprises receptor-mediated biological rhythms synchronisation. Among other functions mentioned later belong anti-gonadotropic, immunotropic and non-receptor-mediated antioxidative effects. Melatonin is said to have also antineoplastic properties. Its anti-aging effect is discutable.

Analgesics↗

Antibodies against oxidized LDL--theory and clinical use.

Modification of low density lipoprotein (LDL) particles due to oxidation, glycation and binding of advanced glycation end-products (AGEs) or malondialdehyde (MDA, a final product of lipid peroxidation) is considered most important in the process of atherogenesis. Oxidatively modified LDL are distinguished by another receptor type, which was discovered on the surface of macrophages and was called the scavenger receptor. Uncontrolled intake of LDL converts macrophages to foam cells; their accumulation under the vascular endothelium is considered as the first stage of atherosclerosis. Oxidation of LDL is a complex process taking place in both the extra- and intracellular space. At the end of this oxidative process, modified LDL particles show chemotactic, cytotoxic and immunogenic properties. Oxidized LDL express a large number of epitopes and cause production of polyclonal autoantibodies against these products, especially against apoB100 modified by MDA and 4-hydroxynonenal. IgoxLDL (antibodies against oxidized LDL) can be demonstrated either directly in intimal lesions or as a component of circulating immune complexes. IgoxLDL do not form a homogeneous group but a varied mixture of antibodies-isoantibodies caused by HDL and LDL polymorphism, antibodies against the lipid phase of LDL and antibodies against modified apoB100 of the immunoglobulin class IgA or IgG. Antibodies against oxLDL were found in many diseases other than atherosclerosis such as diabetes mellitus, renovascular syndrome, uremia, rheumatic fever, morbus Bechtjerev or lupus erythematodes. Newborns have practically the same levels of IgoxLDL as their mothers; however, these values did not differ from those in the healthy population of non-pregnant women of the same age. The decrease in IgoxLDL titer was very slow and lasted many months; that is why this parameter cannot be considered suitable for describing the rapid changes during oxidative stress of the organism. Positive correlation of IgoxLDL with antiphospholipids and other antibodies was repeatedly demonstrated; their determination can thus be used as a marker for the description of total production of autoantibodies in various diseases. The changes and correlations of IgoxLDL, anti-beta-2-glycoprotein I IgG and antiphospholipid antibodies support the immunological link between thrombotic and atherosclerotic processes in the human body.

Arteriosclerosis↗

What is the source of free radicals causing hemolysis in stored blood?

The quality of stored blood can be deteriorated by hemolysis caused by free radicals. The purpose of this study was to elucidate whether neutrophile leukocytes are the source of free radicals in stored blood as in hemodialyzed patients. Resuspensions with low (LL) or high (HL) leukocyte concentrations were prepared from samples of twenty healthy volunteers. The samples were incubated for 10 days at 4 degrees C and then for one day at 37 degrees C. Markers of hemolysis and free radical metabolism were examined before and after incubation in LL and HL samples. In spite of the difference of leukocytes counts in LL and HL resuspensions (p<0.0001), the pre-incubation values of all laboratory parameters were practically identical. In post-storage samples, superoxide dismutase and glutathione peroxidase activities did not differ in either group. Reduced glutathione in erythrocytes and extracellular antioxidant capacity were insignificantly lower in HL resuspensions, but the increase of malondialdehyde was much more pronounced in the HL samples (p<0.0001). The degree of hemolysis, expressed as the extracellular increase of potassium (p<0.001), hemoglobin (p<0.05) and lactate dehydrogenase (p<0.05), was higher in the HL samples. Our results support the hypothesis that leukocytes participate in free radical production in stored blood.

Antioxidants↗

Does exogenous melatonin influence the free radicals metabolism and pain sensation in rat?

Melatonin has been shown to play a role in antioxidative defence. We therefore studied its effect on oxidative damage to the rat cerebral cortex evoked by painful stimulation and immobilization-induced stress. Moreover, the effect of melatonin on chronic pain perception was examined. Rats were injected with either a high dose of melatonin (100 mg/kg i.p.) or a vehicle for five days and were subjected to painful stimulation or immobilization stress 30 min after the treatment. To determine the degree of oxidative stress, the levels of free radicals, thiobarbituric acid reactive substances (TBARS) as indicators of lipid peroxidation and glutathione peroxidase (GSHPx) were estimated in somatosensory cortex. Pain perception was measured by the tail-flick and plantar test. Melatonin reduced the level of TBARS previously increased by painful stimulation. Melatonin also exhibited a slight analgesic effect in those animals exposed to painful stimulation but its role in free radical scavenging did not contribute to this effect.

Animals↗

[Antioxidative properties of ascorbic acid].

Vitamin C (ascorbic acid) is an important hydrophilic compound with antioxidative effect. In the introduction the authors describe possible consequences of loss of vitamin C synthetic ability in an evolutionary ancestor of Anthropoidea. Metabolism of this vitamin is described briefly along with possibilities of its supplementation and determination in biological fluids. Highest attention is paid to metabolic effects of vitamin C, respectively to changes which can be observed after its deprivation, or after the supplementation with this vitamin. Protective effect of vitamin C against lipoperoxidation, its role in modulation of immunity and tumorigenesis are described. Many effects of vitamin C can be explained by its antioxidative activity. The authors show that under concrete conditions, administration of vitamin C can be accompanied by a prooxidative effect. Since vitamin C works in cooperation with other antioxidants, its administration in diseases which are followed by oxidative stress is move effective when used in combined preparations.

Animals↗

[Antioxidants and protection of the skin against the effect of ultraviolet rays].

Ultraviolet radiation causes increase of production of the reactive oxygen species in the human skin, which are responsible for oxidative stress and damage of many important cellular components in the target tissue. The complex of antioxidants represents the major protective system against the oxidative damage of the skin. Many antioxidants, namely vitamin E, can be successfully used in photoprotection.

Antioxidants↗

Anticipation of acute stress in isoprenaline-sensitive and - resistant rats: strain and gender differences.

The effect of stress anticipation was studied in two inbred Wistar rat strains with high and low sensitivity to isoprenaline. The animals were exposed to tail-flick and 4-hr water immersion restraint stress on two consecutive days. On the first day stress was applied to one group and the next day to the anticipation group. The changes in adrenal, heart and spleen weights, tail-flick latency, incidence of gastric ulcers, and the antioxidant defense system in the sensorimotor cortex were compared with two non-stressed control groups. Anticipatory stress decreased adrenal weights. The content of thiobarbituric acid reactive substances (TBARS) was increased both in acute and anticipatory stress; superoxide dismutase, glutathione peroxidase, and antioxidative capacity were increased in anticipatory stress only. Stress anticipation decreased the pain threshold in the isoprenaline-sensitive and increased in the isoprenaline-resistant rats and led to more frequent gastric ulcers in the isoprenaline-resistant group. Significant sex differences were observed both in adrenal weights and TBARS content. The relative adrenal weights were negatively correlated with the TBARS content. We suggest that the outcome of anticipatory stress may depend upon the relation between the hormonal and antioxidant functions of the adrenals and that anticipation-induced activation of antioxidant enzymes may ameliorate the acute stress response. Anticipation itself was found to be a stronger stressor than physical acute stress.

Analysis of Variance↗

The effect of hemodialysis and acetate-free biofiltration on anemia.

The authors monitored, for a period of 12 months, anemia-, nutrition-, and free radical-related parameters and the rHuEPO dose required to maintain target hemoglobin (Hb) in 20 patients with chronic renal failure. Ten patients each were randomized for treatment by either acetate-free biofiltration (AFB) or low-flux hemodialysis (HD). At baseline, Hb levels were 102+/-2 (AFB) vs. 98+/-2 g/L (HD) (not significant difference, NS), the rHuEPO dose was 4050+/-976 vs. 5100+/-1538 lU/week (NS). Compared with baseline and with HD, lower rHuEPO doses were required during AFB at months 8, 9, 10 and 11, and 12 when they were 2100+/-510 (AFB) vs. 6000+/-1153 (HD), p=0.008. Prealbumin, transferrin and cholinesterase levels rose in the AFB group. Kt/V, albumin, transferrin saturation, aluminium, bicarbonate in serum, superoxide dismutase and glutathione peroxidase in erythrocytes, and malondialdehyde and antioxidant capacity in plasma did not differ between the AFB and HD groups. In terms of anemia control, AFB using an AN69 membrane was found to be more advantageous than low-flux HD, AFB improves some nutritional parameters. The compared methods do not differ in their effect on lipid peroxidation and the antioxidant system.

Adult↗

[Effect of antioxidant therapy on indicators of free radical activity in workers at risk of lead exposure].

The authors administered to 36 workers exposed to lead, for four weeks the preparation Prolong which contains vitamin C, vitamin E, beta-carotene, selenium, zinc and chromium and investigated the effect on indicators of free radicals. A statistically significant increase of the following occurred: superoxide dismutase (p < 0.001), glutathione peroxidase (p < 0.01), an increase of the total antioxidant capacity (p < 0.01) and an increase of uricaemia (p < 0.05). Based on these results the authors consider supplementation with antioxidants indicated in workers exposed to lead.

Adult↗